Asthma is a heterogeneous disease characterized by symptoms of chronic inflammation and airway structural and functional changes. It affects about 300 million people worldwide and causes 250 000 deaths annually, but its symptoms can be greatly relieved by regular use of inhaled glucocorticoids (GCs). GCs exert their function through interacting with glucocorticoid receptors (GRs). Diosgenin is a naturally occurring steroidal saponin abundantly present in many medicinal plants, including Dioscorea nipponica, which shares a similar steroidal structure with GC. In this study, ovalbumin (OVA)-induced asthmatic mice and primary tracheal epithelial cells (TECs) were used as research models. ELISAs were applied to measure the secretion of TNF-α, IL-1β, and IL-6, while quantitative PCR and western blotting were applied to evaluate expression of GRs SLPI, TTP, GILZ, MKP-1, and NF-B. Our data demonstrated that diosgenin suppressed the secretion of TNF-α, IL-1β, and IL-6 by enhancing the expression of GRs, SLPI, GILZ, and MKP-1, and inhibiting the expression of HSP70. These data provide some evidence on the molecular mechanism of diosgenin, which might facilitate its clinical applications.
Atorvastatin reduces the incidence of cardiovascular events. However, the effects of atorvastatin on platelet aggregation are unknown.
Blood samples were obtained from 126 healthy volunteers. Prepared isolated platelet suspensions were adjusted with saline to three different concentrations of 100 x 109, 300 x 109, and 600 x 109 platelets/L. Platelet samples were incubated with atorvastatin (10–7 mol/L, 10–6 mol/L or 10–5 mol/L), and stimulated with ADP (10 µmol/L), arachidonic acid (0.5 mmol/L), collagen (2 µg/mL), and epinephrine (1 mg/mL). The maximal amplitude of aggregation and the curve slope were measured by electric impedance aggregometry.
Atorvastatin inhibited platelet aggregation at moderate (300 x 109/L) and high (600 x 109/L) concentrations. However, an inhibitory effect of atorvastatin at low concentrations (100 x 109/L) was not observed.
The study shows that atorvastatin inhibits platelet aggregation in vitro, and this inhibitory effect is related to platelet concentrations.
To explore the possible correlation between uric acid levels and leukoaraiosis (LA).
This cross-sectional study enrolled patients who presented with some neurological discomfort (e.g. dizziness, headache, mild cognitive impairment). Potential demographic and clinical risk factors associated with LA, including sex, age, hypertension, diabetes mellitus, smoking, alcohol consumption, dyslipidaemia, plasma fibrinogen, D-dimer, uric acid, and homocysteine, were investigated using univariate and multivariate logistic regression analyses.
A total of 268 patients were enrolled in the study and divided into the LA group (n = 164) and the non-LA group (n = 104). Compared with the non-LA group, uric acid was significantly higher in the LA group (mean ± SD: 356.49 ± 121.85 µmol/l versus 289.96 ± 102.98 µmol/l). Multivariate logistic regression analyses showed that uric acid was an independent risk factor for LA (odds ratio 1.285; 95% confidence interval 1.062, 1.556).
Hyperuricaemia was an independent risk factor for leukoaraiosis in Chinese patients.
To investigate the expression and clinicopathological significance of the oestrogen receptor (ER) in non-small cell lung cancer (NSCLC).
ER expression was examined by immunohistochemical staining of tumour tissue and adjacent normal lung tissue from 67 NSCLC patients. The relationships between ER expression and clinicopathological features were analysed.
A higher percentage of NSCLC tissues (28/67, 41.79%) than adjacent normal lung tissues (10/55, 18.18%) were ER positive. ER expression correlated with tumour differentiation but not with gender, age, tumour histological type, tumour size, lymph node metastasis, or clinical TNM staging. The median survival times of patients with ER-positive (n = 28) and -negative (n = 39) tumours were 36 and 27 months, respectively. The 1-, 3-, and 5-year survival rates were higher for patients with ER-positive tumours than for patients with ER-negative tumours.
ER expression could be a useful prognostic biomarker and therapeutic target for patients with NSCLC.
To develop a simple, effective, time-saving and low-cost fluorescence protein microarray method for detecting serum alpha-fetoprotein (AFP) in patients with hepatocellular carcinoma (HCC).
Non-contact piezoelectric print techniques were applied to fluorescence protein microarray to reduce the cost of prey antibody. Serum samples from patients with HCC and healthy control subjects were collected and evaluated for the presence of AFP using a novel fluorescence protein microarray. To validate the fluorescence protein microarray, serum samples were tested for AFP using an enzyme-linked immunosorbent assay (ELISA).
A total of 110 serum samples from patients with HCC (n = 65) and healthy control subjects (n = 45) were analysed. When the AFP cut-off value was set at 20 ng/ml, the fluorescence protein microarray had a sensitivity of 91.67% and a specificity of 93.24% for detecting serum AFP. Serum AFP quantified via fluorescence protein microarray had a similar diagnostic performance compared with ELISA in distinguishing patients with HCC from healthy control subjects (area under receiver operating characteristic curve: 0.906 for fluorescence protein microarray; 0.880 for ELISA).
A fluorescence protein microarray method was developed for detecting serum AFP in patients with HCC.
To quantify T helper (Th)17 cells and determine interleukin (IL)-17A levels in peripheral blood mononuclear cell (PBMC) culture and vitreous fluid from patients with type 2 diabetes mellitus (T2DM) with diabetic retinopathy (DR).
Th17 cell frequency and IL-17A concentrations in PBMCs from 60 patients with T2DM with DR, 30 without DR and 30 sex- and age-matched healthy individuals were measured by flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. IL-17A levels in vitreous fluid from 31 eyes with proliferative DR and diabetic macular oedema (DR group) and 32 eyes with an epiretinal membrane and macular hole (control group) that underwent vitrectomy were also examined by ELISA.
Compared with the control group, the proportion of Th17 cells and IL-17A concentrations in PBMCs were significantly increased in patients without DR but decreased in those with DR. IL-17A concentrations and Th17 cell frequency in PBMCs tended to decrease with DR severity and were negatively correlated with body mass index, T2DM duration and glycated haemoglobin. Additionally, vitreous fluid IL-17A levels were significantly elevated in patients with DR compared with those of the control group.
We conclude that disturbances in Th17 cells and IL-17A levels are possibly associated with DR.
To determine whether frozen shoulder heals equally well in patients with and without diabetes and whether dependency on insulin affects the outcome.
We retrospectively examined 178 patients with idiopathic frozen shoulder; 27 patients had diabetes. We evaluated range of motion, pain, and functional results. The mean follow-up was 9.7 years (SD, 7.1 years).
In the presence of frozen shoulder, range of motion did not differ between patients with and without diabetes. At follow-up, range of motion in all directions of both the affected and unaffected shoulders of patients with diabetes was inferior to that of patients without diabetes. Among patients with diabetes, range of motion of the once-frozen shoulder reached the level of the unaffected shoulder. Patients with and without diabetes experienced similar pain except during exertion. The Constant–Murley score was not significantly different between the two groups, and insulin dependency did not lead to worse outcomes.
Frozen shoulder heals well in patients with diabetes.
Taccaoside, a steroidal saponin, has been shown to be cytotoxic, although the mechanism of cytotoxicity remains unclear. This study examined the effect of taccaoside on the human hepatocellular carcinoma (HCC) cell lines SMMC-7721 and Bel-7404.
The antiproliferative effect of taccaoside were measured using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. Cells were stained with Hoechst 33258 to observe morphology. Cell cycle and apoptosis were analysed by flow cytometry. Caspase activation was detected using specific assays, and PARP, Bax and Bcl-2 expression were analysed using western blotting.
Taccaoside showed antiproliferative effect on HCC cell lines growth in a concentration- and time-dependent manner. Taccaoside arrested cell cycle in the G2/M phase and induced caspase-dependent apoptosis. Western blotting indicated that taccaoside upregulated Bax expression and downregulated Bcl-2 expression. PARP cleavage was observed following taccaoside treatment.
This study showed that taccaoside may inhibit HCC cell proliferation by inducing apoptosis.
To determine the expression and clinical significance of plasma miR-335 in patients with acute ischemic stroke (AIS) and investigate its association with calmodulin (CaM) expression.
Plasma miR-335 and CaM expression levels in patients with AIS and healthy controls were examined. Correlations between miR-335, CaM, and National Institutes of Health Stroke Scale scores were also analysed. Furthermore, the potential regulatory function of miR-335 on CaM expression was investigated.
Plasma miR-335 levels were significantly lower in AIS and negatively correlated with NIHSS scores. The converse was observed for plasma CaM levels. Plasma miR-335 and CaM levels were negatively correlated. Plasma miR-335 was confirmed as a novel biomarker for AIS diagnosis and an independent predictor of AIS. Up-regulation of miR-335 suppressed CaM protein expression, and CaM was confirmed as a direct target of miR-335.
Plasma miR-335 was down-regulated in AIS patients and represents a potential noninvasive circulating biomarker.
To investigate the cardiometabolic effects of a severe hypothyroid state induced by withdrawal of thyroid hormone replacement before radioactive iodine therapy.
Patients with thyroid cancer who were scheduled to receive radioactive iodine ablation were enrolled. Cardiometabolic parameters were measured using blood samples taken immediately before levothyroxine withdrawal, 4 weeks following withdrawal (on radiotherapy day), and 4 weeks following reinstitution of levothyroxine.
Out of 48 patients (age 49.4 ± 10.5 years; 77.1% [37/48] female), the severe hypothyroid state induced by levothyroxine withdrawal significantly aggravated the majority of lipid parameters, particularly in patients with a greater number of metabolic syndrome components. Fasting plasma glucose levels and homeostatic model assessment values for insulin resistance and β-cell function significantly decreased following levothyroxine withdrawal. Serum high-sensitivity C-reactive protein, fibrinogen and cystatin C levels significantly decreased, and homocysteine levels increased during the severe hypothyroid state. All of these changes were reversed by levothyroxine reinstitution.
Severe hypothyroid state induced pronounced changes in cardiometabolic parameters. Further studies should identify the long-term effects of changes in these parameters on cardiovascular morbidity and mortality in relation to thyroid disease.
To investigate the association between serpin family E member 1 (SERPINE1) -844 A/G and -675 4G/5G polymorphisms and chronic obstructive pulmonary disease (COPD) in a Chinese Han population.
SERPINE1 -844 A/G and -675 4G/5G polymorphisms were assessed by polymerase chain reaction-restriction fragment length polymorphism sequencing of genomic DNA from patients with COPD and healthy smoking controls.
Out of 140 patients with COPD and 100 controls, all SERPINE1 -844 and -675 polymorphisms were in Hardy-Weinberg equilibrium. Differences in SERPINE1 -675 4G and 5G allele frequencies were statistically significant between the COPD and control groups (odds ratio [OR] 1.45, 95% confidence interval [CI] 1.00, 2.09), but there was no significant between-group difference in SERPINE1 -844 A and G allele frequencies. The SERPINE1 -675 4G/4G genotype was associated with COPD (OR 1.87, 95% CI 1.06, 3.32 [binary logistic regression]). Haplotype analysis showed that COPD was associated with SERPINE1 -844G/4G (OR 2.11, 95% CI 1.32, 3.38) and SERPINE1 -844G/5G (OR 0.66, 95% CI 0.45, 0.95).
The SERPINE1 -675 polymorphism, but not SERPINE1 -844 polymorphism, was associated with susceptibility to COPD in a Chinese Han population.
To demonstrate that postoperative computed tomography (CT) is not needed if navigation is used to determine the rotational position of the femoral component during total knee replacement (TKR).
Preoperative CT, navigational, and postoperative CT data of 70 TKR procedures were analysed. The correlation between the rotational angulation of the femur measured by CT and that measured by perioperative navigation was examined. The correlation between the femoral component rotation determined by navigation and that determined by CT was also assessed.
The mean femoral rotation determined by navigation was 2.64° ± 4.34°, while that shown by CT was 6.43° ± 1.65°. Postoperative rotation of the femoral component shown by CT was 3.09° ± 2.71°, which was closely correlated with the angle obtained through the intraoperative transepicondylar axis by navigation (Pearson’s R = 0.930).
Navigation can be used to collect the preoperative, intraoperative, and postoperative data and final position of the TKR. The rotation of the femoral component can be determined using navigation without the need for CT.
To investigate the potential use of high mobility group box 1 (HMGB1) as a marker for the surgical course following surgery for colorectal cancer (CRC).
Patients with advanced CRC undergoing open colorectal surgery who did not develop postsurgical complications were enrolled in the study. Blood samples were taken preoperatively and at 1 day, 1 week and 3 weeks after surgery for the measurement of the white blood cell count, serum C-reactive protein, serum amyloid A and HMGB1.
Data from 21 patients were analysed. HMGB1 levels changed significantly during the surgical course, increasing from a preoperative median of 6.8 ng/ml to 12.1 ng/ml at 1 day postoperatively, and then decreasing to 8.1 ng/ml at 1 week postoperatively and 4.0 ng/ml at 3 weeks postoperatively. These changes were similar to but were not completely correlated with the changes seen in the other markers.
Serum HMGB1 may be a potential marker to monitor the surgical course in patients undergoing surgery for CRC, although further studies are warranted before it can be introduced into routine clinical practice.
The pathomechanism of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is unknown; however, a small subgroup of patients has shown muscarinic antibody positivity and reduced symptom presentation following anti-CD20 intervention. Given the important roles of calcium (Ca2+) and acetylcholine (ACh) signalling in B cell activation and potential antibody development, we aimed to identify relevant single nucleotide polymorphisms (SNPs) and genotypes in isolated B cells from CFS/ME patients.
A total of 11 CFS/ME patients (aged 31.82 ± 5.50 years) and 11 non-fatigued controls (aged 33.91 ± 5.06 years) were included. Flow cytometric protocols were used to determine B cell purity, followed by SNP and genotype analysis for 21 mammalian TRP ion channel genes and nine mammalian ACh receptor genes. SNP association and genotyping analysis were performed using ANOVA and PLINK analysis software.
Seventy-eight SNPs were identified in nicotinic and muscarinic acetylcholine receptor genes in the CFS/ME group, of which 35 were in mAChM3. The remaining SNPs were identified in nAChR delta (n = 12), nAChR alpha 9 (n = 5), TRPV2 (n = 7), TRPM3 (n = 4), TRPM4 (n = 1) mAChRM3 2 (n = 2), and mAChRM5 (n = 3) genes. Nine genotypes were identified from SNPs in TRPM3 (n = 1), TRPC6 (n = 1), mAChRM3 (n = 2), nAChR alpha 4 (n = 1), and nAChR beta 1 (n = 4) genes, and were located in introns and 3' untranslated regions. Odds ratios for these specific genotypes ranged between 7.11 and 26.67 for CFS/ME compared with the non-fatigued control group.
This preliminary investigation identified a number of SNPs and genotypes in genes encoding TRP ion channels and AChRs from B cells in patients with CFS/ME. These may be involved in B cell functional changes, and suggest a role for Ca2+ dysregulation in AChR and TRP ion channel signalling in the pathomechanism of CFS/ME.
To describe the protocol of the SURgically induced Metabolic effects on the Human GastroIntestinal Tract (SURMetaGIT) study, a clinical pan-omics study exploring the gastrointestinal tract as a central organ driving remission of type 2 diabetes mellitus (T2DM) after Roux-en-Y gastric bypass (RYGB). The main points considered in the study’s design and challenges faced in its application are detailed.
This observational, longitudinal, prospective study involved collection of gastrointestinal biopsy specimens, faeces, urine, and blood from 25 obese women with T2DM who were candidates for RYGB (20 patients for omics assessment and 5 for omics validation). These collections were performed preoperatively and 3 and 24 months postoperatively. Gastrointestinal transcriptomics; faecal metagenomics and metabolomics; plasma proteomics, lipidomics, and metabolomics; and biochemical, nutritional, and metabolic data were assessed to identify their short- and long-term correlations with T2DM remission.
Data were collected from 20 patients before and 3 months after RYGB. These patients have nearly completed the 2-year follow-up assessments. The five additional patients are currently being selected for omics data validation.
The multi-integrated pan-omics approach of the SURMetaGIT study enables integrated analysis of data that will contribute to the understanding of molecular mechanisms involved in T2DM remission after RYGB.
To determine the validity and reliability of a Latvian version of the National Institutes of Health Stroke Scale (LV-NIHSS) for evaluating Latvian stroke patients.
The adaption of the LV-NIHSS followed standard methods used for the adaption and validation of clinical assessment tools. The scale validity was tested by comparison with the Glasgow Coma Scale (GCS) and the modified Rankin scale (mRs). The reliability of the LV-NIHSS was evaluated by intra-rater and inter-rater agreement using intra-class correlation coefficient (ICC) analysis.
A total of 296 stroke patients and 101 control subjects were evaluated. The mean age of the overall study population was 73.6 years (range, 37 – 94 years; 227 [57.2%] were female). The mean LV-NIHSS score of the patients with stroke was 8.4 ± 6.2. In terms of construct validity of the LV-NIHSS, it correlated with the GCS (r = –0.571) and mRs (r = 0.755). In terms of the reliability of the LV-NIHSS, the inter-rater agreement had an ICC of 0.99 and the intra-rater agreement had an ICC of 0.99.
The adaption of LV-NIHSS was successful and the evaluation showed that the scale was valid and reliable for evaluating Latvian stroke patients.
To measure therapeutic inertia by characterizing prescription patterns using secondary data obtained from the nationwide diabetes mellitus pay-for-performance (DM-P4P) programme in Taiwan.
Using reimbursement claims from Taiwan’s National Health Insurance Research Database, a nationwide retrospective cohort study was undertaken of patients with diabetes mellitus who participated in the DM-P4P programme from 2006–2008. Glycosylated haemoglobin results were used to evaluate modifications in therapy in response to poor diabetes control. Prescription patterns were used to assign patients to either a therapeutic inertia group or an intensified treatment group. Therapeutic inertia was defined as the failure to act on a known problem.
The research sample comprised of 168 876 patients with diabetes mellitus who had undergone 899 135 tests. Of these, 37.4% (336 615 visits) of prescriptions were for a combination of two types of drug and 27.7% (248 788 visits) were for a combination of three types of drug. The proportion of patients in the intensified therapy group who were prescribed more than two types of drug was considerably higher than that in the therapeutic inertia group.
In many cases in the therapeutic inertia group only a single type of hypoglycaemic drug was prescribed or the dosage remained unchanged.
To investigate the proportion of circulating invariant natural killer T (iNKT) cells in four body health types.
In this cross-sectional study, participants were classified into four body health types according to the body mass index and metabolic status: metabolically healthy and normal weight (MHNW), metabolically unhealthy but normal weight (MUNW), metabolically healthy but obese (MHO), or metabolically unhealthy and obese (MUO). Demographic and clinical characteristics were measured, and the homeostasis model assessment of insulin resistance (HOMA-IR) and visceral adiposity index (VAI) were calculated. The proportion of circulating iNKT cells was also evaluated by flow cytometry.
The study enrolled 41 MHNW, 37 MUNW, 30 MHO, and 43 MUO participants. Compared with the MHNW group, the MUNW, MHO, and MUO groups had significantly lower iNKT cell proportions. The iNKT cell proportion was significantly higher in the MHO group than the MUNW and MUO groups. The iNKT cell proportion was inversely correlated with high-sensitivity C-reactive protein, HOMA-IR, and VAI values.
The proportion of iNKT cells was lower in people (lean or obese) with excessive visceral fat accumulation, suggesting that iNKT cell deficiency may be involved in the pathophysiology of obesity-related metabolic disorders.
To investigate the effect of sperm DNA fragmentation on the fertilization rate, embryo development and pregnancy outcome of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) in a cohort of Chinese couples.
Infertile couples that had undergone assisted reproductive technology at our centre between January 2011 and December 2013 were included in this retrospective study. Fractions of prepared sperm samples were evaluated for sperm DNA fragmentation on the day of oocyte recovery.
Of the 550 couples selected, 415 had undergone IVF and 135 ICSI. Sperm DNA fragmentation rate was significantly negatively correlated with the fertilization rate in the ICSI cycles but not the IVF cycles. No association was found between sperm DNA fragmentation and cleavage rate or good quality embryo formation rates in IVF or ICSI cycles. Receiver operating characteristic (ROC) curve analysis showed that the sperm DNA fragmentation rate was a statistically significant prognostic indicator of the clinical fertilization rate in ICSI cycles; a rate > 22.3% was associated with a lower fertilization rate following ICSI compared with a rate ≤ 22.3%.
High values of sperm DNA fragmentation were associated with a low fertilization rate following ICSI but were not associated with alterations in pregnancy or live birth rates in either ICSI or IVF in this cohort of Chinese couples.
To evaluate whether gamma-glutamyl transpeptidase to platelet ratio index (GPRI) can diagnose the extent of liver fibrosis in Chinese patients with chronic hepatitis B (CHB) infection.
This prospective observational study used liver biopsy results as the gold standard to evaluate the ability of GPRI to predict hepatic fibrosis compared with two other markers, the aspartate aminotransferase (AST) to platelet ratio index (APRI) and fibrosis-4 score (FIB-4). The clinical and demographic factors that affected GPRI, independent of liver fibrosis, were assessed using multivariate linear regression analyses.
This study enrolled 312 patients with CHB. GPRI had a significantly positive correlation with liver fibrosis stage and the correlation coefficient was higher than that for APRI and FIB-4. The areas under the receiver operating curves for GPRI for significant fibrosis, bridging fibrosis, and cirrhosis were 0.728, 0.836, and 0.842, respectively. Of the three indices, GPRI had the highest diagnostic accuracy for bridging fibrosis and cirrhosis. Age, elevated AST and elevated total bilirubin levels were independent determinants of increased GPRI.
GPRI was a more reliable laboratory marker than APRI and FIB-4 for predicting the stage of liver fibrosis in Chinese patients with CHB.
To evaluate the immunohistochemical staining pattern of caudal type homeobox 2 (CDX2) protein in germ cell tumours (GCTs) of the testis.
This study reassessed archival tissue samples collected from patients diagnosed with primary and metastatic testicular GCTs for CDX2 immunoreactivity using standard immunohistochemical techniques. Positive nuclear immunostaining was evaluated with regard to both the staining intensity and the extent of the staining.
Tissue sections from primary and metastatic testicular GCTs (n = 104), germ cell neoplasia in situ (GCNis) (n = 5) and benign testicles (n = 15) were analysed. The GCNis and benign testicular tissues showed no immunoreactivity for CDX2. Strong and diffuse staining of CDX2 was demonstrated only in the mature colonic epithelium of teratomas in both primary and metastatic GCTs. CDX2 positivity in other tumours (one pure yolk sac tumour, one yolk sac component of a mixed GCT and one pure seminoma) was infrequent, and was only weak and focal.
CDX2 immunostaining should be interpreted based on both the staining intensity and the extent of staining so as not to cause misdiagnosis. Teratomas with colonic-type epithelium should be considered in the differential diagnosis if a metastatic tumour with an unknown primary shows prominent CDX2 immunostaining.
The results of segmental venous resection (VR) combined with pancreatoduodenectomy (PD) are controversial but may be promising. Few studies have described reconstruction of the portal/superior mesenteric vein (PV/SMV) with the iliac vein harvested from donation after cardiac death (DCD).
From January 2014 to April 2016, PD combined with segmental excision of the PV/SMV (VR group) was performed in 21 patients with adenocarcinoma of the head of the pancreas (ADHP). The authors established a new technique of venous reconstruction using the iliac vein from DCD and analysed patients’ long-term survival.
The tumour dimensions and tumour staging were greater and the operation time was longer in the VR than PD group; however, no differences in the resection degree, blood loss, complications, reoperation rate, or mortality rate were found. The median survival was similar between the VR and PD groups. The long-term patency of the donor iliac vein was 90%. The degree of resection was a strong predictor of long-term survival.
Segmental PV/SMV resection combined with PD is applicable to selective patients with venous invasion by ADHP if R0 resection has probably been achieved. An iliac vein obtained by DCD provides an effective graft for venous reconstruction.
Coronary artery dilations (CDs), a subgroup of coronary artery anomalies (CAAs), are relatively rare but important cardiac pathologies. They are considered to be linked to coronary atherosclerosis in most cases.
The demographic data, multi-slice computed tomographic coronary angiography data, coronary calcium score, and ascending aortic diameter (AAD) of 1538 patients were reviewed. In total, 197 (12.8%) patients (166 men, 31 women; age 15 – 84 years; mean 55.78 ± 12.32 years) with CAAs were identified, and 81 (5.3%) patients (70 men, 11 women; age 27 – 80 years; mean 56.63 ± 12.06 years) had CDs. Multiple regression and correlation analyses were performed in all 1538 patients to predict the association between the AAD and the presence of CD and thus their correlation with atherosclerosis.
The AAD was significantly larger in patients with than without CAAs and CDs. Male sex was significantly more prevalent in patients with CAAs and CDs. According to the multiple logistic regression model, male sex increased the risk of CD by 2.650 and the risk of CAA by 2.017, while hyperlipidaemia decreased the risk of CAA by 0.681. While a moderately weak correlation between the AAD and age was observed in patients with CDs, no correlation was found between the AAD and coronary calcium score.
Although the natural history and physiopathology of CDs is not yet fully understood, the present study shows an association between the AAD and the presence of CDs but a lack of association between atherosclerosis and CDs.
In Japan, stroke care is provided through medical cooperation and standardized treatment. However, various factors affect mortality in the hyperacute phase. The present study investigated factors associated with death within 24 h after admission for acute stroke.
Among 2335 patients admitted within 24 h after stroke onset from 1 January 2007 to 31 December 2012, a total of 139 deaths occurred. Forty-eight deaths occurred within 24 h after admission. We retrospectively examined the clinical features of these 48 patients.
The overall mortality rate was 6.0%. When the initial 72-h period was divided into ≤24 h (Period I), >24 to 48 h (Period II), and >48 to 72 h (Period III), deaths were significantly more frequent in Period I than in the other two periods. The frequency of intracerebral haemorrhage (ICH) was also significantly higher in Period I than in the other two periods. Factors significantly associated with death from ICH were systolic blood pressure, hematoma volume, and surgery.
The mortality rate was low among patients with stroke transported to the authors’ medical center within 24 h of onset. Blood pressure management and the timing of determining indications for surgery are important factors in acute haemorrhagic stroke care.
This study investigated the use of prosthetic condensed polytetrafluoroethylene (cPTFE) for laparoscopic ventral hernia repair (LVHR) in an outpatient community-hospital setting.
Patients underwent LVHR with cPTFE at one of three community hospitals. Primary endpoint was hernia recurrence at 1-year postoperatively. Secondary endpoints included pain, surgical site infection, medical/surgical complications, and patient-reported outcomes.
This study included 65 females and 52 males, aged 46.6 ± 13.2 years (mean ± SD; range 18–84 years). Mean prosthetic size was 413.8 ± 336.11 cm2 (range 165–936 cm2). Mean follow-up was 30 months (range 12–46 months). Hernia recurrence rate was 4.3%. Rate of hospitalization in the first postoperative week was 2.6%. Early and late secondary endpoint complication rates were 24.8% and 27.4%, respectively; pain was the most common complication, followed by seroma (8.5%).
Outpatient LVHR using cPTFE is feasible in community hospitals. Complication rates were similar to previous reports, and the seroma rate was markedly lower.
To investigate the protective effects of epigallocatechin-3-gallate (EGCG), a major polyphenol source in green tea, against hepatic ischaemia–reperfusion injury in mice.
The partial hepatic ischaemia–reperfusion injury model was created by employing the hanging-weight method in C57BL/6 male mice. EGCG (50 mg/kg) was administered via an intraperitoneal injection 45 min before performing the reperfusion. A number of markers of inflammation, oxidative stress, apoptosis and liver injury were measured after the ischaemia–reperfusion injury had been induced.
The treatment groups were: sham-operated (Sham, n = 10), hepatic ischaemia–reperfusion injury (IR, n = 10), and EGCG with ischaemia–reperfusion injury (EGCG-treated IR, n = 10). Hepatic ischaemia–reperfusion injury increased the levels of biochemical and histological markers of liver injury, increased the levels of malondialdehyde, reduced the glutathione/oxidized glutathione ratio, increased the levels of oxidative stress and lipid peroxidation markers, decreased B-cell lymphoma 2 levels, and increased the levels of Bax, cytochrome c, cleaved caspase-3, and cleaved caspase-9. Pretreatment with EGCG ameliorated all of these changes.
The antioxidant and antiapoptotic effects of EGCG protected against hepatic ischaemia–reperfusion injury in mice.
To examine if hypoxia inducible factor-1α (HIF-1α) can induce the upregulation of the purinergic receptor P2Y2 (P2Y2) and thereby promote the viability of human hepatocellular carcinoma (HCC) cells under hypoxic conditions.
Archival HCC tumour specimens and corresponding non-cancerous tissues were examined immunohistochemically for P2Y2 protein. A series of in vitro experiments were undertaken using HCC cell lines to determine the effect of hypoxia on HIF-1α and P2Y2 levels, the effect of HIF-1α upregulation on P2Y2 levels, and the effect of P2Y2 upregulation on cell viability under hypoxic conditions.
Human HCC specimens were positive for P2Y2. Hypoxia and upregulated HIF-1α both upregulated the P2Y2 levels in HCC cell lines. P2Y2 upregulation using plasmid transfection resulted in enhanced cell viability under hypoxia. Treatment of HepG2 cells with the selective P2Y2 antagonist MRS2312 downregulated P2Y2 and reduced cell viability in five HCC cell lines. P2Y2 knockdown reduced HepG2 cell viability under hypoxia.
These present results suggest that HCC cells upregulate P2Y2 levels during hypoxia, which in turn promotes their growth. P2Y2 could be a potential therapeutic target for treating HCC.
We planned a cross-sectional analysis to determine the frequency and severity of metabolic acidosis in patients taking topiramate while awaiting craniotomy.
Eighty patients (18 – 65 years) taking topiramate to control seizures while awaiting elective craniotomy were enrolled. Any signs of metabolic acidosis or topiramate-related side effects were investigated. Blood chemistry levels and arterial blood gases, including lactate, were obtained. The severity of metabolic acidosis was defined according to base excess levels as mild or moderate.
Blood gas analysis showed that 71% (n = 57) of patients had metabolic acidosis. The frequency of moderate metabolic acidosis was 56% (n = 45), while that of mild metabolic acidosis was 15% (n = 12). A high respiratory rate was reported in only 10% of moderately acidotic patients.
In patients receiving topiramate, baseline blood gas analysis should be performed preoperatively to determine the presence and severity of metabolic acidosis.
To determine if there was herd protection conferred to unprotected healthcare workers (HCWs) by N95 respirators worn by colleagues.
Data were analysed from a prospective cluster randomized clinical trial conducted in Beijing, China between 1 December 2008 and 15 January 2009. A minimum compliance level (MCL) of N95 respirators for prevention of clinical respiratory illness (CRI) was set based on various compliance cut-offs. The CRI rates were compared between compliant (≥MCL) and non-compliant (<MCL) N95 wearers by ward, and between non-compliant wearers and control subjects who did not wear masks.
Data were analysed from 949 HCWs who wore N95 respirators and 125 HCWs who did not wear masks. At 50% MCL there were no significant differences in the CRI rates between compliant and non-compliant N95 wearers by ward. In multivariate analysis, the CRI rate in non-compliant HCWs was significantly lower compared with controls (relative risk 0.26; 95% confidence interval 0.08, 0.82).
This study suggests herd protection from use of N95 respirators by colleagues within a hospital ward.
To compare the effects of saddle, lumbar epidural and caudal blocks on anal sphincter tone using anorectal manometry.
Patients undergoing elective anorectal surgery with regional anaesthesia were divided randomly into three groups and received a saddle (SD), lumbar epidural (LE), or caudal (CD) block. Anorectal manometry was performed before and 30 min after each regional block. The degree of motor blockade of the anal sphincter was compared using the maximal resting pressure (MRP) and the maximal squeezing pressure (MSP).
The study analysis population consisted of 49 patients (SD group, n = 18; LE group, n = 16; CD group, n = 15). No significant differences were observed in the percentage inhibition of the MRP among the three regional anaesthetic groups. However, percentage inhibition of the MSP was significantly greater in the SD group (83.6 ± 13.7%) compared with the LE group (58.4 ± 19.8%) and the CD group (47.8 ± 16.9%). In all groups, MSP was reduced significantly more than MRP after each regional block.
Saddle block was more effective than lumbar epidural or caudal block for depressing anal sphincter tone. No differences were detected between lumbar epidural and caudal blocks.
To investigate attentional bias toward happy and sad faces in remitted depressed (RD) patients compared with healthy control (HC) subjects.
This cross-sectional study enrolled RD patients and sex- and age-matched HC subjects. Eye movement data were acquired for all study participants while free viewing a 2 x 2 matrix of emotional faces. The attentional bias toward different emotional faces and whether the attention maintenance components generated attentional bias in the RD patients were analysed by comparing the attentional modes of the RD group with the HC group.
A total of 27 RD patients and 27 HC subjects were analysed in this study. The RD and HC groups exhibited no significant differences toward first fixation location and initial attentional maintenance. In later attentional maintenance, the RD group showed significantly less attentional bias toward happy faces, but there were no significant differences in their attentional bias toward sad faces, compared with the HC group.
This present study showed that the negative attentional bias of RD patients was successfully eased, but their positive attentional bias was still insufficient.
To investigate the incidence of insulin resistance (IR) and diabetes in patients with chronic hepatic schistosomiasis japonica (HSJ) and portosystemic shunts (PSS).
Pre- and post-contrasted computed tomography images obtained from patients with HSJ and control subjects were reviewed by two radiologists who identified and graded any shunting vessels. Anthropometric measurements, hepatic enzymes, lipid profile, blood levels of albumin, glucose, insulin and homeostasis model assessment (HOMA-2) index of all participants were also assessed.
Fifty-two patients with HSJ and 30 control subjects were involved in the study. The coronary, short gastric and perisplenic veins were the most common shunting vessels. There were no significant differences between patients and controls in terms of body mass index or liver function. The degree of shunting vessels, blood glucose, oral glucose tolerance test120/0, insulin, HOMA-2 index, glycosylated haemoglobin, cholesterol, high- and low-density lipoprotein, and C-reactive protein were significantly higher in the patients with IR. A positive correlation was found between the degree of the shunting vessels and the HOMA-2 index.
Patients with chronic HSJ and PSS without liver dysfunction had a high incidence of IR and diabetes. The study showed that PSS and IR are related and therefore patients with PSS should be screened for IR and vice versa.
A retrospective study comparing the diagnostic performance of the BACTEC™ MGIT™ 960 system (M960 system; BD Worldwide, Franklin Lakes, NJ, USA) with Löwenstein–Jensen (L–J) culture to detect mycobacteria in sputum specimens from patients with suspected pulmonary tuberculosis (TB).
Sputum samples were analysed for the presence of acid-fast bacilli (AFB). Samples were inoculated into the M960 system and L–J culture. Positive cultures were examined for the presence of AFB.
The M960 method detected significantly more positive samples than L–J culture (818/1676 [48.8%] vs 692/1676 [41.3%]). Using L–J culture as reference, the sensitivity, specificity, positive predictive and negative predictive values of the M960 system were 91.0%, 76.1%, 77.0% and 92.2%, respectively. The time-to-detection of mycobacteria was 11.78 ± 5.16 days for M960 and 24.17 ± 8.73 days for L–J.
The M960 system had better diagnostic capability than L–J culture. Clinical value may be maximized by combining results from both methods.
To investigate the effect and mechanism of action of metformin on proliferation of a human hypopharyngeal carcinoma cell line (FaDu).
FaDu cells were treated with metformin (25–125 mmol/l). Cell proliferation was evaluated via CCK-8 assay. Real-time quantitative reverse transcription–polymerase chain reaction was used to evaluate microRNA (miR)-21-5p and PDCD4 (programmed cell death 4) expression. PDCD4 protein was quantified by Western blot.
Metformin significantly inhibited FaDu cell proliferation in a dose- (25–100 mmol/l) and time-dependent manner (12 h–36 h), significantly downregulated miR-21-5p, and upregulated PDCD4 mRNA and protein expression.
Metformin significantly inhibited FaDu cell proliferation, possibly via downregulation of miR-21-5p and upregulation of PDCD4.
To design and implement an electromyography (EMG)-based controller for a hand robotic assistive device, which is able to classify the user's motion intention before the effective kinematic movement execution.
Multiple degrees-of-freedom hand grasp movements (i.e. pinching, grasp an object, grasping) were predicted by means of surface EMG signals, recorded from 10 bipolar EMG electrodes arranged in a circular configuration around the forearm 2–3 cm from the elbow. Two cascaded artificial neural networks were then exploited to detect the patient's motion intention from the EMG signal window starting from the electrical activity onset to movement onset (i.e. electromechanical delay).
The proposed approach was tested on eight healthy control subjects (4 females; age range 25–26 years) and it demonstrated a mean ± SD testing performance of 76% ± 14% for correctly predicting healthy users' motion intention. Two post-stroke patients tested the controller and obtained 79% and 100% of correctly classified movements under testing conditions.
A task-selection controller was developed to estimate the intended movement from the EMG measured during the electromechanical delay.
To examine the relationship between nutritional intake and bone mineral density (BMD) in postmenopausal Korean women.
Dietary intake was recorded in postmenopausal Korean women using a semiquantitative questionnaire. The frequency of consumption of various food groups and nutrient intake were calculated. BMD T-scores were measured at the lumbar spine, femoral neck and total hip using dual-energy X-ray absorptiometry. Associations between T-scores and dietary intake were analysed using partial correlation coefficients and multiple linear regression analysis.
A total of 189 postmenopausal women were included in the study. β-Carotene intake was positively correlated with the lumbar spine T-score. Sodium and vitamin C intake were positively associated and folate intake negatively associated with the femoral neck T-score. Sodium, zinc and vitamin C intake were positively correlated and potassium intake was negatively correlated with the total hip T-score. Vegetable intake showed a positive association with the femoral neck and total hip T-scores.
In postmenopausal Korean women, β-carotene, vitamin C, zinc and sodium intakes were positively associated with bone mass. Furthermore, frequency of vegetable consumption was positively associated with femoral neck and total hip T-scores.
To monitor knee skin temperature changes for 12 months following total knee arthroplasty (TKA) and identify potential reasons for any differences in skin temperature and to investigate if there is a relationship between the differential temperature and clinical outcome.
Patients who attended for a unilateral TKA due to primary osteoarthritis between August 2012 and August 2014 were eligible for this prospective study. The skin temperature of both knees was monitored preoperatively and postoperatively using an infrared thermometer. Serum indices and Hospital for Special Surgery (HSS) knee scores were assessed.
Thirty-nine patients were involved in the study. The skin temperature of both knees as well as the differential temperature increased following TKA. Serum haemoglobin, haematocrit and days from surgery showed inverse correlations with the differential temperature, while body mass index and American Society of Anesthesiologists scores showed positive correlations. There was a strong inverse correlation between the differential temperature and HSS. score.
Differential knee skin temperature elevation 12 months post-TKA may be a normal surgical response.
To characterize contemporary attitudes toward global health amongst board-certified obstetricians-gynecologists (Ob-Gyns) in the US.
A questionnaire was mailed to members of the American College of Obstetricians and Gynecologists. Respondents were stratified by interest and experience in global health and group differences were reported.
A total of 202 of 400 (50.5%) surveys were completed; and 67.3% (n = 136) of respondents expressed an interest in global health while 25.2% (n = 51) had experience providing healthcare abroad. Personal safety was the primary concern of respondents (88 of 185, 47.6%), with 44.5% (57 of 128) identifying 2 weeks as an optimal period of time to spend abroad. The majority (113 of 186, 60.8%) cited hosting of local physicians in the US as the most valuable service to developing a nation’s healthcare provision.
Despite high interest in global health, willingness to spend significant time abroad was limited. Concerns surrounding personal safety dovetailed with the belief that training local physicians in the US provides the most valuable service to international efforts. These attitudes and concerns suggest novel solutions will be required to increase involvement of Ob-Gyns in global women’s health.
To investigate the impact of urethral catheterization on uroflow by comparing urodynamic parameters of free uroflowmetry versus pressure-flow study in adult patients with benign prostatic hyperplasia, female stress incontinence, lumbosacral spinal injury or spina bifida.
Each patient was required to perform pressure-flow study immediately following free uroflowmetry. Maximum flow rate (Qmax), average flow rate (Qave), voided volume (VV), Tmax (time to Qmax) and post-voiding residual urine (PVR) were compared between the two tests.
Out of 120 patients, transurethral catheterization significantly impacted uroflow. In male patients with benign prostatic hyperplasia (n = 50), Qmax, Qave and Tmax were significantly different between free uroflow and pressure-flow study. In patients with female stress incontinence (n = 30), there were no statistically significant between-test differences in VV and Tmax, but Qmax, Qave and PVR were significantly different. In patients with spinal injury or spina bifida (n = 40), Qmax, Qave and VV were significantly different between free uroflow and pressure-flow study.
Urethral catheterization adversely impacts uroflow in patients with benign prostatic hyperplasia, female stress incontinence, spinal injury or spina bifida. Free uroflowmetry should be performed before pressure-flow study.
To compare the aortic diameter after isolated aortic valve replacement (AVR) in patients with a bicuspid (BAV) or tricuspid aortic valve (TAV) and an initially normal ascending aorta.
Patients with an ascending aortic diameter of < 45 mm who had undergone isolated AVR were studied. Ultrasonic cardiographic measurements of the ascending aortic diameter made pre- and postoperatively and follow-up data concerning adverse aortic events and death were analyzed.
A total of 613 patients were included in this retrospective study; of these, 211 had a BAV and 402 had a TAV. In both groups, the ascending aorta significantly expanded but was non-aneurysmal during follow-up; however, the difference between the two groups was not significant. Cox regression analysis showed no significant effect associated with the presence of a BAV on adverse aortic events or death.
Dilatation of the ascending aorta was observed after AVR in both groups, but was not more pronounced in patients with a BAV. Long-term follow-up for ascending aortic aneurysm is necessary after AVR in both patients with a BAV and those with a TAV.
To determine the effect-site concentration (Ce) of remifentanil target-controlled infusion required for a smooth inhalational induction without airway irritation using desflurane in a stepwise incremental manner for 50% of patients (EC50) and 95% of patients (EC95).
Patients with an American Society of Anesthesiologists physical status I and II, aged 19–60 years undergoing elective surgery were enrolled in this study. When target Ce of remifentanil was reached, desflurane was inhaled at 4 vol% initially and then it was increased to 8 and 12 vol% at intervals of 30 s. Smooth induction was regarded as an absence of airway irritation signs and excitatory movements. The EC50 and EC95 values for remifentanil were determined using a modified Dixon’s up-and-down method as well as an isotonic regression method with a bootstrapping approach.
The EC50 and EC95 of remifentanil for smooth induction during inhalation of desflurane were 3.40 ng/ml (95% confidence interval [CI] 2.42, 4.38 ng/ml) and 4.31 ng/ml (95% CI 2.15, 5.98 ng/ml), respectively.
Prior administration of remifentanil could provide smooth inhalational induction with desflurane in a stepwise increment.
MicroRNA-154 (miR-154) was previously reported to be downregulated in several types of human cancers and may act as a tumour suppressor. This study aimed to measure miR-154 levels and determine its clinical significance in human glioma.
This retrospective study analysed fresh human glioma specimens and non-neoplastic brain tissues using real-time quantitative reverse transcription–polymerase chain reaction to determine the relative levels of miR-154. The association between miR-154 levels and various clinicopathological characteristics and survival was analysed.
A total of 115 patients with gliomas and 115 non-neoplastic brain tissues were examined. MiR-154 levels were significantly downregulated in gliomas compared with non-neoplastic brain tissues. Low levels of miR-154 were associated with high World Health Organization grade, large tumour size (≥ 5 cm), a low Karnofsky performance status score (< 80), and a shorter overall survival. Multivariate analyses using the Cox proportional hazards regression model confirmed that decreased miR-154 level was an independent predictor of a poor prognosis.
These results suggest that miR-154 downregulation may be involved in glioma formation and progression, and that miR-154 might serve as a potential prognostic biomarker for patients with this disease.
To investigate whether circulating cell-free (cf)-DNA levels are a useful biomarker for survival in patients with shock in the emergency intensive care unit (EICU).
This prospective observational study enrolled patients admitted to the EICU diagnosed with shock. Blood cf-DNA levels were analysed on admission, and after 24 and 48 h. As a measure of circulating cf-DNA, copy number of the β-globin gene in plasma was assessed using quantitative real-time polymerase chain reaction.
Circulating cf-DNA levels were higher at hospital admission and after 24 h in EICU patients with shock who died than in those who recovered. Change in cf-DNA levels over the first 48 h in critical care was independently associated with 28-day mortality. The critical cut-off value for cf-DNA change over 48 h in predicting 28-day mortality was +16.12% (sensitivity 68.9%, specificity 89.7%).
Increased circulating cf-DNA levels in EICU patients with shock are associated with risk of death and measuring cf-DNA change over 48 h improves risk prediction. The present study suggests that cf-DNA may serve as a viable plasma biomarker of mortality risk in EICU patients with shock.
A double-blind randomised study to evaluate the opioid sparing effect and safety of nefopam when administered via intravenous patient controlled analgesia (PCA) with fentanyl.
Patients planned for elective open laparotomy, were randomly assigned to receive into fentanyl 25 µg/ml (SF group) or nefopam 2.4 mg/ml plus fentanyl 25 µg/ml (NF group). Patients were assessed before surgery and for 24 h postoperatively.
Total PCA fentanyl consumption was significantly lower in the NF group (n = 35) than the SF group (n = 36). Pain scores were significantly lower and patients’ satisfaction with treatment significantly better in the NF group than the SF group. Dry mouth and dizziness were significantly more frequent in the NF group than the SF group. There were no other statistically significant between-group differences in the incidence of adverse events.
Intravenous PCA using nefopam + fentanyl following laparotomy has an opioid sparing effect and is associated with a low incidence of some of the typical opioid related adverse events.
Clinicaltrials.gov Registration No: NCT02596269
To investigate the potential association between serum folate levels and colorectal adenoma (CRA) occurrence and recurrence.
This prospective study measured baseline serum folate levels in outpatients who were screened for CRA using colonoscopy. Participants were then randomly selected to produce one group with CRA and one without CRA. These two subgroups underwent further follow-up observations of colonoscopy to determine the occurrence of new and recurrent CRA.
A total of 1310 participants were screened at baseline: 888 were healthy subjects without CRA; and 422 had CRA. Two subgroups were randomly selected (n = 200 per group) for follow-up. In the overall population, baseline serum folate levels were significantly lower in patients with CRA or advanced CRA (A-CRA) compared with healthy participants without CRA. Similar findings were shown for the follow-up study in terms of the association between CRA and A-CRA occurrence and recurrence and baseline serum folate levels. After controlling for confounders, increased serum folate was associated with a reduced risk of occurrence of CRA (odds ratio [OR] 0.993, 95% confidence interval [CI] 0.924, 1.066) and recurrence of CRA (OR 0.749, 95% CI 0.322, 1.742).
Higher serum folate levels may be protective against CRA and/or A-CRA.
This study evaluated the effects of vaginal and caesarean delivery on internal and external anal sphincter muscle thickness using translabial ultrasonography (TL-US).
This prospective cohort study enrolled nulliparous women who either had vaginal or caesarean deliveries. The thickness of the hypoechoic internal anal sphincter (IAS) and hyperechoic external anal sphincter (EAS) at the 12, 3, 6, and 9 o’clock positions at the distal level were measured before delivery and within 24–48 h after delivery.
A total 105 consecutive women were enrolled in the study: 60 in the vaginal delivery group and 45 in the caesarean delivery group. The IAS muscle thickness at the 12 o’clock position in the vaginal delivery group was significantly thicker before compared with after delivery (mean ± SD: 2.31 ± 0.74 mm versus 1.81 ± 0.64 mm, respectively). The EAS muscle thickness at the 12 o’clock position in the vaginal delivery group was significantly thicker before compared with after delivery (mean ± SD: 2.42 ± 0.64 mm versus 1.97 ± 0.85, respectively).
There was significant muscle thinning of both the IAS and EAS at the 12 o’clock position after vaginal delivery, but not after caesarean delivery.
To investigate the regulation mechanism of T cell immunoglobulin and mucin domain-3 (Tim-3) combined with toll-like receptor 3 (TLR3) or TLR4 on antiviral immune and inflammatory response in patients with chronic hepatitis C virus (HCV) infection.
Patients with chronic HCV infection and healthy control subjects were recruited. Patients received interferon (IFN)-α based therapy. Plasma galectin-9 (Gal-9) was quantitated. Peripheral blood mononuclear cells (PBMCs) were cultured with TLR3 or TLR4 agonists, alone or in combination with Tim-3 antagonist. Levels of IFN-α, TNF-α, and 2'-5' oligoadenylate synthetase (2'-5'OAS), myxovirus resistance protein A (MxA) and suppressor of cytokine 1 (SOCS1) RNA in PBMC cultures were evaluated.
Plasma Gal-9 levels were increased in patients (n = 52) compared with controls (n = 20) and significantly declined at treatment week 12 and 24 weeks post-treatment. IFN-α, 2'-5'OAS, MxA, TNF-α and SOCS1 were upregulated by TLR3 and TLR4 agonists. TNF-α and SOCS1 levels were suppressed by the addition of Tim-3 antagonist.
Tim-3 blockade in combination with TLR activation induces the expression of antiviral molecules without a significant increase in TNF-α or SOCS1.
A retrospective study to determine the relationships between platelet parameters and inflammation and fibrosis of the liver in patients with chronic hepatitis B virus infection (CHB).
Patients with liver biopsy-confirmed CHB were included in the study. Liver fibrosis and inflammation were assessed by histopathology of biopsied liver tissue. Platelet count (PLT), platelet distribution width (PDW) and mean platelet volume (MPV) were determined as part of routine blood tests. The relationship between inflammation and fibrosis and platelet parameters were analysed by multiple linear regression.
The study included 677 patients. PLT and PDW accounted for 20.5% of liver inflammation. PLT and PDW accounted for 18.4% of liver fibrosis.
Platelet parameters can provide valuable information for the assessment of hepatic inflammation and fibrosis.
To investigate the possible association between plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) and the incidence and severity of calcific aortic valve disease (CAVD).
This prospective, cross sectional study involved patients with and without (controls) aortic valve calcification diagnosed by transthoracic echocardiography and dual source computed tomography (DSCT) scan. Aortic valves calcification scores were calculated from DSCT scans and patients were graded: grade 1, no calcification; grade 2, mildly calcified; grade 3, moderately calcified; grade 4, heavily calcified. Plasma PCSK9 levels were measured using an enzyme-linked immunosorbent assay.
Forty patients were grade 1 (controls), 32 were grade 2, 48 were grade 3 and 32 were grade 4. Plasma levels of PCSK9 were significantly different between the four groups and the highest value was observed in the patients with grade 2 calcification. Only low-density lipoprotein cholesterol and lipoprotein (Lp)(a) were associated with the severity of CAVD. Regression analysis showed that age, Lp(a) and PCSK9 were independent predictors of CAVD.
Data from this cross sectional study in a small sample of patients showed that plasma PCSK9 was correlated with the presence of CAVD but not its severity.
To investigate the synergistic effects of combining erlotinib and RNA-interference downregulation of focal adhesion kinase (FAK) expression on the proliferation, apoptosis, invasion and migration of the human gastric adenocarcinoma cell line AGS.
Cells were divided into five experimental groups: Group A, nontransfected control; Group B, transfected with empty vector; Group C, transfected with FAK-shRNA; Group D, erlotinib treatment; Group E, combination erlotinib treatment and transfected with FAK-shRNA. FAK protein levels were confirmed via Western blotting. Cell proliferation (CCK-8 assay, apoptosis (flow cytometry), cell invasion (transwell assay) and migration (scratch assay) were evaluated.
RNA interference significantly decreased FAK protein levels. Cell proliferation, invasion and migration were significantly lower in Groups C, D and E compared with Group A, and significantly lower in Group E than in Groups C and D.
RNA interference effectively silences FAK expression and inhibits malignant cell proliferation and invasion in gastric cancer cells. The effect of FAK inhibition is increased by co-treatment with erlotinib.
The diagnostic validity of clinical airway assessment tests for predicting difficult laryngoscopy in patients requiring endotracheal intubation were evaluated using receiver operating characteristic (ROC) curve analysis and a grey zone approach.
In this prospective observational study, patients were evaluated during a pre-anaesthetic visit. Predictive airway assessment tests (i.e. Modified Mallampati [MMT] classification; upper lip bite test [ULBT]; mouth opening; sternomental distance; thyromental distance [TMD]; neck circumference; neck mobility; height to thyromental distance [HT/TMD]; neck circumference-to-thyromental distance [NC/TMD]) were performed on each patient and LEMON, Naguib, and MACOCHA scores were also calculated. In addition, laryngeal images were acquired and assessed for percentage of glottic opening (POGO) scores. A POGO score of zero was categorized as difficult laryngoscopy.
The incidence of difficult laryngoscopy was 14.4% (35/243). Although seven predictive airway assessments (i.e. MMT classification, ULBT, mouth opening, HT/TMD, NC/TMD, and the LEMON and Naguib models) predicted difficult laryngoscopy by ROC analyses, a grey zone approach showed that the parameters were inconclusive in approximately 70% of patients. From all the tests, the HT/TMD ratio showed the highest sensitivity (80.0%) and ULBT had the highest specificity (95.2%).
Using the grey zone approach, all predictive airway assessment tests showed large inconclusive zones which may explain previous inconsistent results in the prediction of difficult laryngoscopy. Our results suggest that the usefulness of clinical airway evaluation tests for predicting difficult laryngoscopy remains controversial.
ClinicalTrials.gov (NCT01719848)
To determine serum chemerin, vaspin and omentin-1 in overweight and normal weight patients with polycystic ovary syndrome (PCOS) and investigate the possible relationship between these adipokines and metabolic syndrome.
This cross sectional study enrolled women with PCOS and healthy women. Serum chemerin, vaspin and omentin-1 were assessed by enzyme-linked immunosorbent assay methods.
Forty patients with PCOS and 30 healthy controls were included in the study. In the PCOS group, 18 women were overweight (body mass index [BMI] = 25.0–29.9 kg/m2) and 22 had normal weight (BMI = 18.5–24.9 kg/m2). Chemerin, total cholesterol, dehydroepiandrosterone sulphate and free androgen index (FAI) were significantly higher; and high-density lipoprotein cholesterol and sex hormone binding globulin were significantly lower in overweight PCOS patients compared with normal weight PCOS patients. A positive correlation was found between chemerin and BMI, triglyceride, insulin, homeostatic model assessment of insulin resistance and FAI in the PCOS group. There was no difference in serum chemerin, vaspin and omentin-1 between PCOS patients and healthy controls.
Circulating chemerin was increased in overweight compared with normal weight PCOS patients. The most predictive variables for circulating chemerin in PCOS patients were BMI, FAI and age.
To evaluate serum micro RNA-143 (miR-143) levels in patients with sepsis or non-infectious systemic inflammatory response syndrome (SIRS), and investigate its possible diagnostic or prognostic value.
Serum was obtained from patients with sepsis or SIRS and healthy control subjects. Relative miR-143 expression was determined using quantitative real time polymerase chain reaction. The diagnostic and prognostic value of serum miR-143 was evaluated.
Serum miR-143 levels were significantly higher in patients with sepsis (n = 103) than patients with SIRS (n = 95) and healthy controls (n = 40). There were significant positive correlations between serum miR-143 level and SOFA and APACHE II scores in patients with sepsis (r = 0.794 and r = 0.825, respectively). Serum miR-143 had a sensitivity of 78.6% and specificity of 91.6% for distinguishing between sepsis and SIRS. There was no association between serum miR-143 and 28-day survival in patients with sepsis.
Serum miR-143 is elevated in patients with sepsis, and may be a useful biomarker for distinguishing between sepsis and SIRS.
A randomized, double-blind, prospective study to evaluate the effect of anticholinergic drugs on thermoregulation in paediatric patients undergoing ambulatory anaesthesia with ketamine.
Patients were randomized to receive either 0.005 mg/kg glycopyrrolate or the equivalent volume of normal saline (placebo) at 30 min before ketamine anaesthesia. Body temperature was measured tympanically at baseline and at 0, 30, 60 and 90 min postoperatively. The quantity of saliva prodiced during surgery and incidence of fever were recorded.
Body temperature was significantly higher in the glycopyrrolate group (n = 42) than the placebo group (n = 42) at 30, 60 and 90 min after surgery, and higher than baseline at 0, 30, 60 and 90 min after surgery. In the placebo group, body temperature was significantly higher than baseline at 0 and 30 min after surgery. Saliva secretion was significantly lower in the glycopyrrolate group than the placebo group.
Routine premedication with adjunctive anticholinergics should not be considered in paediatric patients receiving ketamine sedation due to the increased risk of fever.
Trial registration number, Clinicaltrials.gov: NCT02430272
To determine potential risk factors that could predict stress fractures over an 8-week basic military training in Chinese male infantry recruits.
Recruits from three infantry units enrolled in this prospective study. At baseline, demographic data, personal history of stress fractures, mean duration of weekly exercise and smoking history were recorded on questionnaires and blood samples taken for analysis of bone turnover biomarkers and genetic factors.
Of the 1516 male recruits who volunteered to participate in the study, 1398 recruits provided data for analysis. In total, 189 stress fracture cases were observed (incidence rate: 13.5%) during the 8-week training period. Recruits with stress fractures had a significantly higher incidence of prior fracture history and lower exercise level prior to enrolment compared with those without stress fractures. A significant difference in both allelic frequency and genotypic distribution of the growth differentiation factor 5 (GDF5) gene rs143383 polymorphism was observed between recruits with and without stress fractures. However, no difference in serum bone turnover biomarkers was detected between groups.
This prospective, cohort study indicates that fracture history, lower exercise level and GDF5 rs143383 may be predictive risk factors for stress fractures in Chinese male infantry recruits.
To investigate the cytotoxic effects of suberanilohydroxamic acid (vorinostat) in combination with arsenic trioxide (ATO) on the human NB4 cell line in vitro.
The rates of cell proliferation following treatment with vorinostat with or without ATO were measured. Flow cytometry of Annexin-V/propidium iodide double-stained cells was used to measure apoptosis. Acridine Orange and ethidium bromide staining was used to observe morphological changes characteristic of apoptosis. Western blot analysis was used to measure protein levels.
Vorinostat and ATO, alone and in combination, inhibited the proliferation of NB4 cells in a time- and dose-dependent manner and the effect was additive. NB4 cells treated with vorinostat + ATO demonstrated greater levels of apoptosis compared with cells treated with either drug alone. Both vorinostat and ATO alone and in combination resulted in lower levels of promyelocytic leukaemia/retinoic acid receptor alpha fusion protein and increased levels of acetyl-histone H3 and acetyl-histone H4 proteins compared with controls. Vorinostat + ATO resulted in lower levels of Akt protein compared with either drug alone.
The combination of vorinostat and ATO inhibited cell proliferation, induced apoptosis, and enhanced the chemosensitivity of NB4 cells. The mechanism might be associated with increasing histone acetylation levels as well as downregulation of the Akt signalling pathway.
Continuous invasive arterial blood pressure (IBP) monitoring remains the gold standard for BP measurement, but traditional oscillometric non-invasive intermittent pressure (NIBP) measurement is used in most low-to-moderate risk procedures. This study compared non-invasive continuous arterial BP measurement using a Nexfin® monitor with NIBP and IBP monitors.
This was a single-centre, prospective, pilot study in patients scheduled for elective orthopaedic surgery. Systolic BP, diastolic BP and mean arterial blood pressure (MAP) were measured by Nexfin®, IBP and NIBP at five intraoperative time-points. Pearson correlation coefficients, Bland–Altman plots and trending ability of Nexfin® measurements were used as criteria for success in the investigation of measurement reliability.
A total of 20 patients were enrolled in the study. For MAP, there was a sufficient correlation between IBP/Nexfin® (Pearson = 0.75), which was better than the correlation between IBP/NIBP (Pearson = 0.70). Bland–Altman analysis of the data showed that compared with IBP, there was a higher percentage error for MAPNIBP (30%) compared with MAPNexfin® (27%). Nexfin® and NIBP underestimated systolic BP; NIBP also underestimated diastolic BP and MAP. Trending ability for MAPNexfin® and MAPNIBP were comparable to IBP.
Non-invasive BP measurement with Nexfin® was comparable with IBP and tended to be more precise than NIBP.
To determine the role of apoptosis inhibition in the prevention of diabetic neuropathy using the antiFas cell surface death receptor (Fas) antagonistic monoclonal antibody ZB4.
This prospective study enrolled patients with type 2 diabetes with and without neuropathy and a group of healthy controls. The serum concentrations of Fas and Fas ligand (FasL) were measured in all study participants using an enzyme-linked immunosorbent assay. The ability of serum from study participants to induce apoptosis was evaluated in a human neuronal cell line using flow cytometry.
A total of 28 healthy subjects and 57 patients with diabetes were enrolled in the study. Serum Fas concentrations were significantly increased in diabetes patients with and without neuropathy compared with the controls. Cells treated with the serum from diabetes patients with neuropathy had significantly higher rates of early apoptosis compared with cells treated with control serum. Monoclonal antibody ZB4 was able to block serum-induced apoptosis.
Serum-induced apoptosis of a human neuronal cell line appeared to be mediated via Fas, which suggests that targeting and inhibiting Fas might offer a therapeutic target for diabetic neuropathy.
To study the apoptosis-inducing effect of the Chinese medicine oridonin in the human oesophageal squamous cell carcinoma cell line EC9706, in vitro.
The effect of oridonin on cell proliferation was studied using the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Effects on the cell cycle and apoptosis were studied by flow cytometry; effects on intracellular Ca2+ concentration were studied by measuring the fluorescence intensity of a fluorescent Ca2+ probe by laser scanning confocal microscopy.
The EC9706 cell-proliferation rate decreased with time and oridonin concentration (10–40 µmol/l). The number of cells in G0 and G1 phases increased significantly following exposure to oridonin for 48 and 72 h respectively, and oridonin was shown to be most effective at inducing apoptosis in EC9706 cells at 40 µmol/l. Compared with the control group, all concentrations of oridonin tested (10–40 µmol/l) significantly increased the Ca2+ fluorescence intensity of EC9706 cells.
Oridonin was shown to inhibit proliferation and induce apoptosis in the human oesophageal squamous cell carcinoma cell line EC9706, in vitro. These data provide preliminary experimental evidence for the anticancer effects of oridonin, which is as a traditional Chinese medicine used to treat various cancers, including oesophageal squamous cell carcinoma. Further studies are required to elucidate the mode of action.
This study assessed image quality and radiation dose of multidetector computed tomography (CT) examination using a standard protocol and a low-voltage protocol.
Patients requiring contrast-enhanced abdominal CT examination were randomly assigned to two groups with different voltage protocols: (i) 120 kV; (ii) an automated attenuation-based tube potential optimization mode (CARE kV). The volume CT dose index (CTDIvol) and dose length product (DLP) were recorded. Image quality was semiquantitatively assessed by two blinded radiologists using a five-point scale.
There were 39 patients in the 120 kV group and 50 patients in the CARE kV group. There was no obvious difference in image quality score between the groups. CARE kV resulted in a voltage reduction to 100 kV in 45 patients and to 80 kV in five patients. CTDIvol and DLP were significantly lower with CARE kV than with the 120 kV protocol.
The use of CARE kV reduces radiation dose with no loss of image quality compared with a standard 120 kV protocol.
To investigate the expression of eukaryotic initiation factor 4 E (eIF4E) in hypopharyngeal carcinoma compared with benign lesions, and the relationships between eIF4E expression and various clinicopathological parameters.
Expression of eIF4E was analysed retrospectively in specimens from hypopharyngeal carcinomas and benign hypopharyngeal lesions using immunohistochemical staining and Western blotting. Tumours were classified using the tumour–node–metastasis staging system and the degree of histological differentiation was assessed.
A total of 55 hypopharyngeal carcinoma and 20 benign specimens were analysed. All the hypopharyngeal carcinoma samples were positive for eIF4E expression on immunohistochemistry, whereas the benign lesions were negative or weakly positive. Semi-quantitative assessment (eIF4E score) showed that eIF4E expression was significatly higher in hypopharyngeal carcinoma than in benign lesions. On Western blotting, eIF4E expression assessed using integrated optical density (IOD) was significantly higher in hypopharyngeal carcinoma than in benign lesions. The eIF4E score and IOD value were significantly associated with tumour stage, lymphatic metastasis and degree of differentiation. The IOD value was significantly higher in recurrent compared with initial cases.
eIF4E may play an important role in the development and metastasis of hypopharyngeal carcinoma;its expression may be helpful in establishing the diagnosis, stage and prognosis of this tumour type.
To investigate the association between the genotypes, sequence variations and phylogenetic origins of strains of Helicobacter pylori with gastric cancer in Chinese patients.
Strains of H. pylori were isolated from patients with chronic gastritis and gastric cancer. Genotypes of the cagA and vacA genes were determined using polymerase chain reaction. Sequence analysis was used to detect variations in the 3' and 5' regions of cagA, and to detect known polymorphisms in cagE. A phylogenetic tree was constructed based on the analysis of seven housekeeping genes.
A total of 67 strains of H. pylori were analysed. Nearly all strains of H. pylori carried cagA (65/67; 97.0%), an East Asia type of the cagA 3' region (63/65; 96.9%) and the vacA intermediate (i)1 genotype (65/67; 97.0%). None of the H. pylori strains examined had sequence variations in the 5' region of cagA or cagE. Phylogenetic analyses, however, revealed that strains of H. pylori from gastric cancer tended to cluster together.
Virulent strains of H. pylori were highly prevalent, but virulent genotypes of H. pylori associated with gastric cancer were not detected in this geographical region.
To investigate the postoperative analgesic effects of parecoxib for uvulopalatopharyngoplasty (UPPP).
Patients with obstructive sleep apnoea syndrome who underwent UPPP were randomly divided into two groups. In group A, the incision-local block was performed with 5 ml of 0.5% ropivacaine injected subcutaneously before the end of surgery, then 20 ml of physiological saline was injected intravenously every 12 h for 2 days. In group B, in addition to the incision-local block, 40 mg parecoxib was injected intravenously 30 min before the end of UPPP and 40 mg parecoxib was injected intravenously every 12 h for 2 days. Postoperative pain was measured using a visual analogue scale (VAS). Adverse reactions were recorded.
A total of 40 patients were randomized (n = 20 per group). Under resting conditions, the mean ± SD VAS pain scores were significantly higher in group A compared with group B at 24 h and 48 h after UPPP (24 h 4.0 ± 0.8 versus 2.6 ± 0.6; 48 h 3.8 ± 0.7 versus 2.4 ± 0.5; respectively). Under swallowing conditions, the mean ± SD VAS pain scores were significantly higher in group A compared with group B at 8 h, 24 h and 48 h after UPPP. Postoperative adverse reactions were similar in the two groups.
Intravenous parecoxib combined with incision-local ropivacaine provided effective postoperative analgesia for patients with obstructive sleep apnoea syndrome, undergoing UPPP.
To investigate the influence of recombinant human CD40 ligand (rhCD40L) on the biological behaviour of breast cancer cells.
MDA-MB-23l and MDA-MB-435 treated with rhCD40L were observed for changes in the cell cycle, in membrane proteins, and in mRNA levels of B cell lymphoma-extra-large (Bcl-xl), Bcl-2 associated X protein (Bax) and regulated upon activation, normal T cell expressed and secreted (RANTES). Effects of rhCD40L on cell proliferation in the presence or absence of interferon (IFN)- (500 IU/ml) and/or doxorubicin (20 ng/ml) were also determined.
rhCD40L dose-dependently inhibited cell proliferation. Combination of rhCD40L with IFN- or doxorubicin potentiated the inhibitory activity. After treatment, an increase in cells entering the G1 phase of the cell cycle was observed, with a significant decrease in the number entering the S phase. Levels of several membrane proteins including CD95L and CD120a were also increased. Reverse transcription–polymerase chain reaction revealed an increase in the Bax/Bcl-xl mRNA ratio and an increase in RANTES.
rhCD40L treatment of breast cancer cells mediates a variety of anti-tumour effects, not only by direct cytotoxic activity but also by upregulation of adhesion molecules, co-stimulators and cytokines to rectify T cell immunity.
To evaluate the relationship between plasma N-terminal prohormone B-type natriuretic peptide (NT-proBNP) and weaning outcomes, and the ability of NT-proBNP level to predict weaning success, in cancer patients with pulmonary complications undergoing noncardiac major surgeries.
Patients who were mechanically ventilated following postoperative respiratory failure were enrolled. NT-proBNP levels at the end of a 2-h spontaneous breathing trial were measured. Weaning was considered a success in patients who completed the trial and maintained spontaneous breathing following extubation for >48 h.
Out of 29 patients, 22 patients weaned successfully but weaning failed in 7 patients. Plasma NT-proBNP was significantly higher in the weaning failure group than in the weaning success group. For predicting weaning success, the optimal NT-proBNP threshold value at the end of the spontaneous breathing trial was <448 ng/l (receiver operating characteristic analysis; sensitivity 68.18%, specificity 85.71%, positive predictive value 93.7% and negative predictive value 46.2%).
Measuring NT-proBNP at the end of a spontaneous breathing trial may assist in predicting weaning success, as a noninvasive, quantitative and repeatable indicator of cardiac stress in patients with postsurgical respiratory failure.