Over the past decades, cancer has become one of the toughest challenges for health professionals. The epidemiologists are increasingly directing their research efforts on various malignant tumor worldwide. Of note, incidence of cancers is on the rise more quickly in developed countries. Indeed, great endeavors have to be made in the control of the life-threatening disease. As we know it, pancreatic cancer (PC) is a malignant disease with the worst prognosis. While little is known about the etiology of the PC and measures to prevent the condition, so far, a number of risk factors have been identified. Genetic factors, pre-malignant lesions, predisposing diseases and exogenous factors have been found to be linked to PC. Genetic susceptibility was observed in 10% of PC cases, including inherited PC syndromes and familial PC. However, in the remaining 90%, their PC might be caused by genetic factors in combination with environmental factors. Nonetheless, the exact mechanism of the two kinds of factors, endogenous and exogenous, working together to cause PC remains poorly understood. The fact that most pancreatic neoplasms are diagnosed at an incurable stage of the disease highlights the need to identify risk factors and to understand their contribution to carcinogenesis. This article reviews the high risk factors contributing to the development of PC, to provide information for clinicians and epidemiologists.

The aim of the present study was to accurately evaluate the association of Sox2 expression with the survival of patients with digestive tract cancers. Relevant literatures were identified by comprehensively searching databases including the Pubmed, Embase, CBMdisc, and Wanfang (up to October 2014). A meta-analysis was performed to clarify the association between Sox2 expression and overall survival or clinicopathological parameters of patients with digestive tract cancers (esophageal, gastric, and colorectal cancers). The results showed a significant association between high Sox2 expression and poor overall survival in patients with digestive tract carcinomas (HR=1.55, 95% CI=1.04–2.31), especially for patients with esophageal cancer (HR=2.04, 95%CI=1.30–3.22), colorectal cancer (HR=1.40, 95% CI=1.04–1.89), and digestive tract adenocarcinoma (HR=1.80, 95% CI=1.12–2.89), for Europeans (HR=1.98, 95% CI=1.44–2.71) or patients who did not receive neoadjuvant treatment (HR=1.73, 95% CI=1.10–2.72). Furthermore, Sox2 over-expression was highly correlated with vascular invasion (OR=1.86, 95% CI=1.25–2.77) and poor differentiation (OR=1.88, 95% CI=1.14–3.08), especially in esophageal and colorectal cancers. In conclusion, Sox2 expression may serve as a novel prognostic factor for patients with digestive tract cancers. Over-expression of Sox2 that is correlated with vascular invasion and poor differentiation suggests poor outcomes of patients with digestive tract cancers.

Accumulating studies explored the clinicopathologic and prognostic value of programmed death ligand-1 (PD-L1) in non-small cell lung cancer (NSCLC), but the results were controversial. We therefore conducted a meta-analysis to evaluate the predictive role of PD-L1 in NSCLC patients. We systematically collected relevant studies from PubMed, Embase, Web of Science and China National Knowledge Infrastructure. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) for overall survival (OS), and odd ratios (ORs) with 95% CIs for clinicopathologic factors were calculated. A total of 15 studies involving 3605 patients were included in this meta-analysis. The results showed no prognostic role of PD-L1 in the whole patients (HR=1.60, 95% CI: 0.88–2.89, P=0.123). Subgroup analysis showed that PD-L1 was associated with decreased OS in Asian patients (HR=2.00, 95% CI: 1.55–2.57, P<0.001). Among all the clinicopathologic factors, PD-L1 overexpression was significantly in relevance with poor tumor cell differentiation (HR=1.84, 95% CI: 1.49–2.28, P<0.001), late stage (HR=1.21, 95% CI: 1.02–1.43, P=0.026) and anaplastic lymphoma kinase (ALK) translocation (HR=2.63, 95% CI: 1.08–6.40, P=0.034), but not with other factors. In conclusion, our meta-analysis demonstrated that PD-L1 has a prognostic role in Asian patients with NSCLC.

Hypoxia-inducible factor-1 alpha (HIF-1α) plays a vital role in the initiation, evaluation and prognosis in lung cancer. The prognostic value of HIF-1α reported in diverse study remains disputable. Accordingly, a meta-analysis was implemented to further understand the prognostic role of HIF-1α in lung cancer. The relationship between HIF-1α and the clinicopathological characteristics and prognosis of lung cancer were investigated by a meta-analysis. PubMed and Embase were searched from their inception to January 2015 for observational studies. Fixed-effects or random-effects meta-analyses were used to calculate odds ratios and 95% confidence intervals of different comparisons. A total of 20 studies met the criteria. The results showed that HIF-1α expression in lung cancer tissues was significantly higher than that in normal lung tissues. Expression of HIF-1α in patients with squamous cell carcinoma was significantly higher than that of patients with adenocarcinomas. Similarly, non-small cell lung cancer (NSCLC) patients had higher HIF-1α expression than small cell lung cancer (SCLC) patients. Moreover, lymph node metastasized tissues had higher HIF-1α expression than non-lymph node metastasized tissues. A high level HIF-1α expression was well correlated with the expression of vascular endothelial growth factor and epidermal growth factor receptor in the NSCLC. Notably, NSCLC or SCLC patients with positive HIF-1α expression in tumor tissues had lower overall survival rate than patients with negative HIF-1α expression. It was suggested that HIF-1α expression may be a prognostic biomarker and a potential therapeutic target for lung cancer.

Thymosin β4 (Tβ4) is a key factor in cardiac development, growth, disease, epicardial integrity, blood vessel formation and has cardio-protective properties. However, its role in murine embryonic stem cells (mESCs) proliferation and cardiovascular differentiation remains unclear. Thus we aimed to elucidate the influence of Tβ4 on mESCs. Target genes during mESCs proliferation and differentiation were detected by real-time PCR or Western blotting, and patch clamp was applied to characterize the mESCs-derived cardiomyocytes. It was found that Tβ4 decreased mESCs proliferation in a partial dose-dependent manner and the expression of cell cycle regulatory genes c-myc, c-fos and c-jun. However, mESCs self-renewal markers Oct4 and Nanog were elevated, indicating the maintenance of self-renewal ability in these mESCs. Phosphorylation of STAT3 and Akt was inhibited by Tβ4 while the expression of RAS and phosphorylation of ERK were enhanced. No significant difference was found in BMP2/BMP4 or their downstream protein smad. Wnt3 and Wnt11 were remarkably decreased by Tβ4 with upregulation of Tcf3 and constant β-catenin. Under mESCs differentiation, Tβ4 treatment did not change the expression of cardiovascular cell markers α-MHC, PECAM, and α-SMA. Neither the electrophysiological properties of mESCs-derived cardiomyocytes nor the hormonal regulation by Iso/Cch was affected by Tβ4. In conclusion, Tβ4 suppressed mESCs proliferation by affecting the activity of STAT3, Akt, ERK and Wnt pathways. However, Tβ4 did not influence the in vitro cardiovascular differentiation.

Cytosolic retinoic acid-inducible gene I (RIG-I) is an important innate immune RNA sensor and can induce antiviral cytokines, e.g., interferon-β (IFN-β). Innate immune response to hepatitis B virus (HBV) plays a pivotal role in viral clearance and persistence. However, knowledge of the role that RIG-I plays in HBV infection is limited. The woodchuck is a valuable model for studying HBV infection. To characterize the molecular basis of woodchuck RIG-I (wRIG-I), we analyzed the complete coding sequences (CDSs) of wRIG-I, containing 2778 base pairs that encode 925 amino acids. The deduced wRIG-I protein was 106.847 kD with a theoretical isoelectric point (pI) of 6.07, and contained three important functional structures [caspase activation and recruitment domains (CARDs), DExD/H-box helicases, and a repressor domain (RD)]. In woodchuck fibroblastoma cell line (WH12/6), wRIG-I-targeted small interfering RNA (siRNA) down-regulated RIG-I and its downstrean effector–IFN-β transcripts under RIG-I’ ligand, 5’-ppp double stranded RNA (dsRNA) stimulation. We also measured mRNA levels of wRIG-I in different tissues from healthy woodchucks and in the livers from woodchuck hepatitis virus (WHV)-infected woodchucks. The basal expression levels of wRIG-I were abundant in the kidney and liver. Importantly, wRIG-I was significantly up-regulated in acutely infected woodchuck livers, suggesting that RIG-I might be involved in WHV infection. These results may characterize RIG-I in the woodchuck model, providing a strong basis for further study on RIG-I-mediated innate immunity in HBV infection.

Lipooligosacharide (LOS) of Neisseria gonorrhoeae (gonococci, GC) is involved in the interaction of GC with host cells. Deletion of the alpha-oligosaccharide (alpha-OS) moiety of LOS (lgtF mutant) significantly impairs invasion of GC into epithelial cell lines. GC opacity (Opa) proteins, such as OpaI, mediate phagocytosis and stimulate chemiluminescence responses in neutrophils in part through interaction with members of the carcinoembryonic antigen (CEA) family, which includes CEACAM3 (CD66d), a human neutrophil specific receptor for phagocytosis of bacteria. In the present work, we examined the effects of OpaI-expressing lgtF mutant on phagocytosis by HeLa-CEACAM3 cells and chemiluminescence responses in neutrophils. The results showed that lgtF mutant even expressing OpaI completely lost the ability to promote either phagocytosis mediated by CEACAM3 interaction in HeLa cells or chemiluminescence responses in neutrophils. These data indicated that Opa proteins in the lgtF mutant, which might result from the conformational change, cannot be functional.

SRT1720, a new discovered drug, was reported to activate silent information regulator 1 (SIRT1) and inhibit the chondrocyte apoptosis. However, the underlying mechanism remains elusive. In the present study, the chondrocytes were extracted from the cartilage tissues of New Zealand white rabbits, cultured in the presence of sodium nitroprusside (SNP) (2.5 mmol/L) and divided into five groups: 1, 5, 10, and 20 μmol/L SRT1720 groups and blank control group (0 μmol/L SRT1720). MTT assay was used to detect the chondrocyte viability and proliferation, and DAPI staining and flow cytometry to measure the chondrocyte apoptosis. The expression levels of SIRT1, p53, NF-κB/p65, Bax, and peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α) were detected by Western blotting and the expression levels of SIRT1, type II collagen, and aggrecan mRNA by RT-PCR. The results showed that in the SRT1720-treated groups, the nuclei of chondrocytes were morphologically intact and had uniform chromatin. In the blank control group, nuclear rupture into debris was observed in chondrocytes. With the SRT1720 concentration increasing, the chondrocyte viability increased, the apoptosis rate decreased, the protein expression levels of SIRT1 and PGC-1α and the mRNA expression levels of type II collagen and aggrecan increased ({ptP}<0.05), and the expression levels of p53, NF-κB and bax decreased (P<0.05). It was suggested that SRT1720 inhibits chondrocyte apoptosis by activating the expression of SIRT1 via p53/bax and NF-κB/PGC-1α pathways.

Hydrogen peroxide (H₂O₂) and free radicals cause oxidative stress, which induces cellular injuries, metabolic dysfunction, and even cell death in various clinical abnormalities. Fullerene (C₆₀) is critical for scavenging oxygen free radicals originated from cell metabolism, and reduced glutathione (GSH) is another important endogenous antioxidant. In this study, a novel water-soluble reduced glutathione fullerene derivative (C₆₀-GSH) was successfully synthesized, and its beneficial roles in protecting against H₂O₂-induced oxidative stress and apoptosis in cultured HEK 293T cells were investigated. Fourier Transform infrared spectroscopy and ¹H nuclear magnetic resonance were used to confirm the chemical structure of C₆₀-GSH. Our results demonstrated that C₆₀-GSH prevented the reactive oxygen species (ROS)-mediated cell damage. Additionally, C₆₀-GSH pretreatment significantly attenuated H₂O₂-induced superoxide dismutase (SOD) consumption and malondialdehyde (MDA) elevation. Furthermore, C₆₀-GSH inhibited intracellular calcium mobilization, and subsequent cell apoptosis via bcl-2/bax-caspase-3 signaling pathway induced by H₂O₂ stimulation in HEK 293T cells. Importantly, these protective effects of C₆₀-GSH were superior to those of GSH. In conclusion, these results suggested that C₆₀-GSH has potential to protect against H₂O₂-induced cell apoptosis by scavenging free radicals and maintaining intracellular calcium homeostasis without evident toxicity.

The association between high-density lipoprotein cholesterol (HDL-C) and mortality in patients with acute aortic dissection (AAD) is unclear. From January 2007 to January 2014, a total of 928 consecutive AAD patients who were admitted within 48 h after the onset of symptoms were enrolled in the study. Patients were divided into two groups according to whether serum HDL-C level was below the normal lower limit or not. The Cox proportional hazard regression model was used to identify the predictive value of HDL-C for in-hospital mortality in patients with AAD. As compared with normal HDL-C group (n=585), low HDL-C group (n=343) had lower levels of systolic blood pressure and hemoglobin and higher levels of leukocyte, alanine aminotransferase, blood glucose, blood urea nitrogen, creatinine and urea acid. Low HDL-C group had significantly higher in-hospital mortality than normal HDL-C group (21.6% vs. 12.6%, log-rank=10.869, P=0.001). After adjustment for baseline variables including demographics and biologic data, the increased risk of in-hospital mortality in low HDL-C group was substantially attenuated and showed no significant difference (adjusted hazard ratio, 1.23; 95% confidence interval, 0.86–1.77; P=0.259). Low HDL-C is strongly but not independently associated with in-hospital mortality in patients with AAD.

Although the development of the 2009 SpA classification criteria by Assessment of SpondyloArthritis international Society (ASAS) represents an important step towards a better definition of the early disease stage particularly in axial spondyloarthritis (axSpA), the specificity of the criteria has been criticized these days. As the commonest zoonotic infection worldwide, human brucellosis can mimic a large number of diseases, including SpA. This study was performed to determine the frequency of rheumatologic manifestations in patients with brucellosis and the chance of misdiagnosing them as having axSpA in central China. The results showed that clinical manifestations of axSpA could be observed in brucellosis. Over half of patients had back pain, and one fifth of the patients with back pain were less than 45 years old at onset and had the symptom for more than 3 months. Two young males were falsely classified as suffering from axSpA according to the ASAS criteria, and one with MRI proved sacroiliitis was once given Etanercept for treatment. Therefore, differential diagnosis including human brucellosis should always be kept in mind when applying the ASAS criteria, even in traditionally non-endemic areas.

Infection of schistosomiasis japonica may eventually lead to liver fibrosis, and no effective antifibrotic therapies are available but liver transplantation. Hedgehog (HH) signaling pathway has been involved in the process and is a promising target for treating liver fibrosis. This study aimed to explore the effects of pentoxifylline (PTX) on liver fibrosis induced by schistosoma japonicum infection by inhibiting the HH signaling pathway. Phorbol12-myristate13-acetate (PMA) was used to induce human acute mononuclear leukemia cells THP-1 to differentiate into macrophages. The THP-1-derived macrophages were stimulated by soluble egg antigen (SEA), and the culture supernatants were collected for detection of activation of macrophages. Cell Counting Kit-8 (CCK-8) was used to detect the cytotoxicity of the culture supernatant and PTX on the LX-2 cells. The LX-2 cells were administered with activated culture supernatant from macrophages and(or) PTX to detect the transforming growth factor-β gene expression. The mRNA expression of shh and gli-1, key parts in HH signaling pathway, was detected. The mRNA expression of shh and gli-1 was increased in LX-2 cells treated with activated macrophages-derived culture supernatant, suggesting HH signaling pathway may play a key role in the activation process of hepatic stellate cells (HSCs). The expression of these genes decreased in LX-2 cells co-cultured with both activated macrophages-derived culture supernatant and PTX, indicating PTX could suppress the activation process of HSCs. In conclusion, these data provide evidence that PTX prevents liver fibrogenesis in vitro by the suppression of HH signaling pathway.

Vertical sleeve gastrectomy (VSG) is becoming more and more popular among the world. Despite its dramatic efficacy, however, the mechanism of VSG remains largely undetermined. This study aimed to test interferon (IFN)-γ secretion n of mesenteric lymph nodes in obese mice (ob/ob mice), a model of VSG, and its relationship with farnesoid X receptor (FXR) expression in the liver and small intestine, and to investigate the weight loss mechanism of VSG. The wild type (WT) mice and ob/ob mice were divided into four groups: A (WT+Sham), B (WT+VSG), C (ob/ob+Sham), and D (ob/ob+VSG). Body weight values were monitored. The IFN-γ expression in mesenteric lymph nodes of ob/ob mice pre- and post-operation was detected by flow cytometry (FCM). The FXR expression in the liver and small intestine was detected by Western blotting. The mouse AML-12 liver cells were stimulated with IFN-γ at different concentrations in vitro. The changes of FXR expression were also examined. The results showed that the body weight of ob/ob mice was significantly declined from (40.6±2.7) g to (27.5±3.8) g on the 30th day after VSG (P<0.05). At the same time, VSG induced a higher level secretion of IFN-γ in mesenteric lymph nodes of ob/ob mice than that pre-operation (P<0.05). The FXR expression levels in the liver and small intestine after VSG were respectively 0.97±0.07 and 0.84±0.07 fold of GAPDH, which were significantly higher than pre-operative levels of 0.50±0.06 and 0.48±0.06 respectively (P<0.05). After the stimulation of AML-12 liver cells in vitro by different concentrations of IFN-γ (0, 10, 25, 50, 100, and 200 ng/mL), the relative FXR expression levels were 0.22±0.04, 0.31±0.04, 0.39±0.05, 0.38±0.05, 0.56±0.06, and 0.35±0.05, respectively, suggesting IFN-γ could distinctly promote the FXR expression in a dose-dependent manner in comparison to those cells without IFN-γ stimulation (P<0.05). It was concluded that VSG induces a weight loss in ob/ob mice by increasing IFN-γ secretion of mesenteric lymph nodes, which then increases the FXR expression of the liver and small intestine.

Swelling-activated chloride currents (I_Cl.swell) are thought to play a role in several physiologic and pathophysiologic processes and thus represent a target for therapeutic approaches. However, the mechanism of I_Cl.swell regulation remains unclear. In this study, we used the whole-cell patch-clamp technique to examine the role of protein kinase C (PKC) in the regulation of I_Cl.swell in human atrial myocytes. Atrial myocytes were isolated from the right atrial appendages of patients undergoing coronary artery bypass and enzymatically dissociated. I_Cl.swell was evoked in hypotonic solution and recorded using the whole-cell patch-clamp technique. The PKC agonist phorbol dibutyrate (PDBu) enhanced I_Cl.swell in a concentration-dependent manner, which was reversed in isotonic solution and by a chloride current inhibitor, 9-anthracenecarboxylicacid. Furthermore, the PKC inhibitor bis-indolylmaleimide attenuated the effect and 4α-PDBu, an inactive PDBu analog, had no effect on I_Cl.swell. These results, obtained using the whole-cell patch-clamp technique, demonstrate the ability of PKC to activate I_Cl,swell in human atrial myocytes. This observation was consistent with a previous study using a single-channel patch-clamp technique, but differed from some findings in other species.

The clinical effects of two different methods–high-viscosity cement percutaneous vertebroplasty (PVP) and low-viscosity cement percutaneous kyphoplasty (PKP) in the treatment of osteoporotic vertebral compression fractures (OVCFs) were investigated. From June 2010 to August 2013, 98 cases of OVCFs were included in our study. Forty-six patients underwent high-viscosity PVP and 52 patients underwent low-viscosity PKP. The occurrence of cement leakage was observed. Pain relief and functional activity were evaluated using the Visual Analog Scale (VAS) and Oswestry Disability Index (ODI), respectively. Restoration of the vertebral body height and angle of kyphosis were assessed by comparing preoperative and postoperative measurements of the anterior heights, middle heights and the kyphotic angle of the fractured vertebra. Nine out of the 54 vertebra bodies and 11 out of the 60 vertebra bodies were observed to have cement leakage in the high-viscosity PVP and low-viscosity PKP groups, respectively. The rate of cement leakage, correction of anterior vertebral height and kyphotic angles showed no significant differences between the two groups (P>0.05). Low-viscosity PKP had significant advantage in terms of the restoration of middle vertebral height as compared with the high-viscosity PVP (P<0.05). Both groups showed significant improvements in pain relief and functional capacity status after surgery (P<0.05). It was concluded that high-viscosity PVP and low-viscosity PKP have similar clinical effects in terms of the rate of cement leakage, restoration of the anterior vertebral body height, changes of kyphotic angles, functional activity, and pain relief. Low-viscosity PKP is better than high-viscosity PVP in restoring the height of the middle vertebra.

Axl encodes the tyrosine-protein kinase receptor, participating in the proliferation and migration of many cells. This study examined the role of Axl in functions of endothelial progenitor cells (EPCs). Axl was detected by RT-PCR and Western blotting in both placentas and EPCs from normal pregnancy and preeclampsia patients. The Axl inhibitor, BMS777-607, was used to inhibit the Axl signalling pathway in EPCs. Cell proliferation, differentiation, migration and adhesion were measured by CCK-8 assay, cell differentiation assay, Transwell assay, and cell adhesion assay, respectively. Results showed the expression levels of Axl mRNA and protein were significantly higher in both placentas and EPCs from preeclampsia patients than from normal pregnancy (P<0.05). After treatment with BMS777-607, proliferation, differentiation, migration and adhesion capability of EPCs were all significantly decreased. Our study suggests Axl may play a role in the function of EPCs, thereby involving in the pathogenesis of preeclampsia.

p53 gene plays an important role in apoptosis, which is necessary for successful invasion of trophoblast cells. The change from an arginine (Arg) to a proline (Pro) at codon 72 can influence the biological activity of p53, which predisposes to an increased risk of recurrent spontaneous abortion (RSA). In order to investigate the association between p53 polymorphism at codon 72 and RSA, we conducted this meta-analysis. Pubmed, Embase and Web of science were used to identify the eligible studies. Odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the strength of the association. Six studies containing 937 cases of RSA and 830 controls were included, and there was one study deviated from Hardy-Weinberg equilibrium (HWE). There was a significant association between p53 polymorphism at codon 72 and RSA in recessive model (Pro/Pro vs. Pro/Arg+Arg/Arg; OR=1.60, 95% CI: 1.14–2.24) and co-dominant model (Pro/Pro vs. Arg/Arg; OR=1.47, 95% CI: 1.02–2.12) whether the study that was deviated from HWE was eliminated or not. A significant association was observed in allelic model (Pro vs. Arg; OR=1.28, 95% CI: 1.04–1.57) after exclusion of the study that was deviated from HWE. No association was noted in recessive model (Pro/Pro+Pro/Arg vs. Arg/Arg; OR=1.05, 95% CI: 0.86–1.30) and co-dominant model (Pro/Arg vs. Arg/Arg; OR=0.96, 95% CI: 0.77–1.19). Subgroup analysis by ethnicity also indicated a significant association between p53 polymorphism at codon 72 and RSA in Caucasian group. No heterogeneity and publication bias were found. Our meta-analysis implied that p53 polymorphism at codon 72 carries high maternal risk of RSA.

Age-related hearing loss (AHL) is one of the most common sensory disorders among elderly persons. The inwardly rectifying potassium channel 5.1 (Kir5.1) plays a vital role in regulating cochlear K⁺ circulation which is necessary for normal hearing. The distribution of Kir5.1 in C57BL/6J mice cochleae, and the relationship between the expression of Kir5.1 and the etiology of AHL were investigated. Forty C57BL/6J mice were randomly divided into four groups at 4, 12, 24 and 52 weeks of age respectively. The location of Kir5.1 was detected by immunofluorescence technique. The mRNA and protein expression of Kir5.1 was evaluated in mice cochleae using real-time polymerase-chain reactions (RT-PCR) and Western blotting respectively. Kir5.1 was detected in the type II and IV fibrocytes of the spiral ligament in the cochlear lateral wall of C57BL/6J mice. The expression levels of Kir5.1 mRNA and protein in the cochleae of aging C57BL/6J mice were down-regulated. It was suggested that the age-related decreased expression of Kir5.1 in the lateral wall of C57BL/6J mice was associated with hearing loss. Our results indicated that Kir5.1 may play an important role in the pathogenesis of AHL.

Wheat dependent exercise-induced anaphylaxis (WDEIA) is a rare but potentially severe food allergy caused by the combination of wheat ingestion and physical exercise. The impact of WDEIA on quality of life (QOL) is unclear. This study characterized the clinical and laboratory features and investigated the QOL in WDEIA patients from Central China. Twenty-eight WDEIA patients were analyzed, and QOL was measured by validated Chinese version Food Allergy Quality of Life Questionnaire-Adult Form (FAQLQ-AF) and Food Allergy Independent Measure (FAIM) after obtaining the diagnosis. The results showed that half of the patients were females. The median onset age was 37 years old. The symptoms occurred within 1 h after wheat ingestion (26/28). Symptoms of anaphylaxis included cutaneous (26/28), respiratory (11/28), gastro-intestinal (5/28) and cardiovascular manifestations (27/28). Skin prick tests were positive to salt soluble (89.3%) and salt insoluble wheat allergen extracts (100%). Positive rate to wheat, gluten and omega-5 gliadin specific IgE was 64.3%, 92.9% and 92.9% respectively. Specific IgE to omega-5 gliadin with a cut-off value 0.83 KU/L offered highly efficient diagnostic criterion for WDEIA (sensitivity: 89.3%; and specificity: 88.9%). The mean scores of FAQLQ-AF and FAIM were 4.70 and 4.98 respectively and level of anti-omega-5 gliadin IgE had positive correlations with FAQLQ scores. Thereby, WDEIA is commonly found in mid-age adults. In most cases, multi-organs especially skin and cardiovascular systems are involved. Salt insoluble wheat allergen skin test and serum specific IgE to gluten and omega-5 gliadin help to diagnose WDEIA. QOL in WDEIA patients is severely impaired.

The levels of Streptococcus (S.) mutans infections in saliva were evaluated and a comparison for specific antibody levels among children with different levels of S. mutans infection was made. The promising epitopic regions of antigen AgI/II (PAc) and glucosyltransferase (GTF) for potential vaccine targets related to S. mutans adherence were screened. A total of 94 children aged 3–4 years were randomly selected, including 53 caries-negative and 41 caries-positive children. The values of S. mutans and those of salivary total secretory immunoglobulin A (sIgA), anti-PAc and anti-Glucan binding domain (anti-GLU) were compared to determine the correlation among them. It was found the level of s-IgA against specific antigens did not increase with increasing severity of S. mutans infection, and the complete amino acid sequence of PAc and GTFB was analyzed using the DNAStar Protean system for developing specific anti-caries vaccines related to S. mutans adherence. A significantly positive correlation between the amount of S. mutans and children decayed, missing, and filled teeth index was observed. No significant difference was detected in specific sIgA against PAc or GLU between any two groups. No significant correlation was found between such specific sIgA and caries index. A total of 16 peptides from PAc as well as 13 peptides from GTFB were chosen for further investigation. S. mutans colonization contributed to early children caries as an important etiological factor. The level of sIgA against specific antigens did not increase with increasing severity of S. mutans infection in children. The epitopes of PAc and GTF have been screened to develop the peptide-based or protein-based anti-caries vaccines.

The purpose of this research was to evaluate the structural stress and deformation of a newly designed onplant miniplate anchorage system compared to a standard anchorage system. A bone block integrated with a novel miniplate and fixation screw system was simulated in a three-dimensional model and subjected to force at different directions. The stress distribution and deformation of the miniplate system and cortical bone were evaluated using the three-dimensional finite element method. The results showed that the stress on the plate system and bone was linearly proportional to the force magnitude and was higher when the force was in a vertical direction (Y-axis). Stress and deformation values of the two screws (screw 1 and 2) were asymmetric when the force was added along Y-axis and was greater in screw 1. The highest deformation value of the screws was 7.5148 μm, much smaller than the limit value. The load was decreased for each single miniscrew, and the ability of the new anchorage system to bear the load was also enhanced to some degree. It was suggested that the newly designed onplant miniplate anchorage system is effective, easily implanted and minimally invasive.

This study aimed to establish a new propofol target-controlled infusion (TCI) model in animals so as to study the general anesthetic mechanism at multi-levels in vivo. Twenty Japanese white rabbits were enrolled and propofol (10 mg/kg) was administrated intravenously. Artery blood samples were collected at various time points after injection, and plasma concentrations of propofol were measured. Pharmacokinetic modeling was performed using WinNonlin software. Propofol TCI within the acquired parameters integrated was conducted to achieve different anesthetic depths in rabbits, monitored by narcotrend. The pharmacodynamics was analyzed using a sigmoidal inhibitory maximal effect model for narcotrend index (NI) versus effect-site concentration. The results showed the pharmacokinetics of propofol in Japanese white rabbits was best described by a two-compartment model. The target plasma concentrations of propofol required at light anesthetic depth was 9.77±0.23 μg/mL, while 12.52±0.69 μg/mL at deep anesthetic depth. NI was 76.17±4.25 at light anesthetic depth, while 27.41±5.77 at deep anesthetic depth. The effect-site elimination rate constant (ke0) was 0.263/min, and the propofol dose required to achieve a 50% decrease in the NI value from baseline was 11.19 μg/mL (95% CI, 10.25–13.67). Our results established a new propofol TCI animal model and proved the model controlled the anesthetic depth accurately and stably in rabbits. The study provides a powerful method for exploring general anesthetic mechanisms at different anesthetic depths in vivo.

The present study investigated the application of echocardiography to evaluation of cardiac dyssynchrony in patients with congestive heart failure (CHF). A total of 348 consecutive CHF patients who were admitted for cardiac resynchronization (CRT) and presented with low ejection fraction (EF) and wide QRS duration were enrolled in this study, along with 388 healthy individuals. Dyssynchrony was assessed based on filling time ratio (FT/RR), left ventricular pre-ejection delay (PED), interventricular mechanical delay (IVMD), longitudinal opposing wall delay (LOWD) and radial septal to posterior wall delay (RSPWD). Response to CRT was defined as a ≥15% increase in EF. The results showed that FT/RR was decreased while PED, IVMD, LOWD and RSPWD were increased in the CHF group compared with the control group (P<0.01). In the CHF group, FT/RR was negatively correlated with the QRS duration, LV end-diastolic diameter (LVESd), LV end-diastolic volume (LVEDV) and LV end-systolic volume (LVESV) (P<0.01), but positively with the LVEF (P<0.01). Additionally, PED, IVMD, LOWD and RSPWD were positively correlated with the QRS duration, LVESd, LVEDV and LVESV (P<0.01), but negatively with the LVEF (P<0.01). The CHF group was divided into three subgroups according to the varying degrees of LVEF. FT/RR decreased successively from the LVEF-1 group to the LVEF-2 group to the LVEF-3 group, while the PED, IVMD, LOWD and RSPWD successively increased in the same order (P<0.01). The CHF group was divided into three subgroups according to the varying degrees of QRS duration, and FT/RR decreased successively in a sequence from the QRS-1 group to the QRS-2 group to the QRS-3 group, while the PED, IVMD, LOWD and RSPWD successively increased in the same order (P<0.01). Speckle tracking radial dyssynchrony ≥130 ms was predictive of an EF response in patients in QRS-1 group (78% sensitivity, 83% specificity), those in QRS-2 group (83% sensitivity, 77% specificity) and in QRS-3 group (89% sensitivity, 79% specificity). In conclusion, echocardiography is a convenient and sensitive method for evaluating cardiac dyssynchrony in patients with CHF.

Differences in arterial stiffness between the two sides of the carotid arteries were investigated using ultrasonic radiofrequency in 88 patients with type 2 diabetes and 70 controls. The compliance coefficient (CC), pulse wave velocity (PWV), intima-media thickness (CIMT) and diameter (CCAD) of the common carotid arteries (CCAs) were measured. The ratio of the left to right CCAs was calculated to provide four indexes: CC ratio, PWV ratio, CIMT ratio and CCAD ratio. In the diabetes group, the PWV on the left side was significantly higher than that on the right side, while the CC on the left side was significantly lower than that on the right side. The bilateral CIMT was thicker and CCAD was wider, the left PWV traveled faster, and the right CC was higher in the diabetes group than in the control group. The PWV ratio between the two groups was significantly different and correlated positively with duration of diabetes and systolic blood pressure (SBP). The differences between the two sides of CCAs in patients with diabetes suggested that disease duration and SBP were important risk factors for arterial stiffness. Identifying the difference could potentially lead to the much earlier diagnosis of arteriosclerosis.

Brown algae are well known as a source of biologically active compounds, especially those having antioxidant activities, such as phlorotannins. In this study we examined the antioxidant activities of crude phlorotannins extracts (CPEs) obtained from Sargassum hemiphyllum (SH) and fractionated according to the molecular weights. When CPEs were administrated at a dose of 30 mg/kg to Kunming mice pre-treated with carbon tetrachloride (CCl₄), the levels of oxidative stress indicators in the liver, kidney and brain were significantly reduced in vivo. All the components of various molecular weight fractions of CPEs exhibited greater scavenging capacities in clearing hydroxyl free radical and superoxide anion than the positive controls gallic acid, vitamin C and vitamin E. Particularly, the components greater than 30 kD obtained from ethyl acetate phase showed the highest antioxidant capacities. These results indicated that SH is a potential source for extracting phlorotannins, the algal antioxidant compounds.

Bi-yuan-ling granule (BLG) is a traditional Chinese medicine compound composed mainly of baicalin and chlorogenic acid. It has been demonstrated to be clinically effective for various inflammatory diseases such as acute rhinitis, chronic rhinitis, atrophic rhinitis and allergic rhinitis. However, the underlying mechanisms of BLG against these diseases are not fully understood. This study aimed to explore the anti-inflammatory and analgesic activities of BLG, and examine its protective effects on mouse acute lung injury (ALI). The hot plate test and acetic acid-induced writhing assay in Kunming mice were adopted to evaluate the pain-relieving effects of BLG. The anti-inflammatory activities of BLG were determined by examining the effects of BLG on xylene-caused ear swelling in Kunming mice, the cotton pellet-induced granuloma in rats, carrageenan-induced hind paw edema and lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. The results showed that BLG at 15.5 mg/g could significantly relieve the pain by 82.5% (P<0.01) at 1 h after thermal stimulation and 91.2% (P<0.01) at 2 h after thermal stimulation. BLG at doses of 7.75 and 15.5 mg/g reduced the writhing count up to 33.3% (P<0.05) and 53.4% (P<0.01), respectively. Additionally, the xylene-induced edema in mice was markedly restrained by BLG at 7.75 mg/g (P<0.05) and 15.5 mg/g (P<0.01). BLG at 5.35 and 10.7 mg/g significantly reduced paw edema by 34.8% (P<0.05) and 37.9% (P<0.05) at 5 h after carrageenan injection. The granulomatous formation of the cotton pellet was profoundly suppressed by BLG at 2.68, 5.35 and 10.7 mg/g by 15.4%, 38.2% (P<0.01) and 58.9% (P<0.001), respectively. BLG also inhibited lung W/D ratio and the release of prostaglandin E2 (PGE2) in ALI mice. In addition, the median lethal dose (LD₅₀), median effective dose (ED₅₀) and half maximal inhibitory concentration (IC₅₀) of BLG were found to be 42.7, 3.2 and 12.33 mg/g, respectively. All the findings suggest that BLG has significantly anti-inflammatory and analgesic effects and it may help reduce the damage of ALI.

The human pregnane X receptor (hPXR) plays a critical role in the metabolism, transport and clearance of xenobiotics in the liver and intestine. The hPXR can be activated by a structurally diverse of drugs to initiate clinically relevant drug-drug interactions. In this article, in silico investigation was performed on a structurally diverse set of drugs to identify critical structural features greatly related to their agonist activity towards hPXR. Heuristic method (HM)-Best Subset Modeling (BSM) and HM-Polynomial Neural Networks (PNN) were utilized to develop the linear and non-linear quantitative structure-activity relationship models. The applicability domain (AD) of the models was assessed by Williams plot. Statistically reliable models with good predictive power and explain were achieved (for HM-BSM, r²=0.881, q_LOO²=0.797, q_EXT²=0.674; for HM-PNN, r²=0.882, q_LOO²=0.856, q_EXT²=0.655). The developed models indicated that molecular aromatic and electric property, molecular weight and complexity may govern agonist activity of a structurally diverse set of drugs to hPXR.

This study aimed to develop a guideline for therapeutic drug monitoring (TDM) of vancomycin. We adopted the new guideline definition from the Institute of Medicine (IOM), adhered closely to the six domains of the Appraisal of Guidelines for Research & Evaluation II (AGREE II), and made recommendations based on systematic reviews. We established a Guideline Steering Group and a Guideline Development Group, formulated 12 questions in the form of Population, Intervention, Comparison, Outcome (PICO) and completed a literature search. As far as we know, we will develop the first evidenced-based guideline for vancomycin TDM under the framework of the Grade of Recommendations Assessment, Development and Evaluation (GRADE).