There have been several epidemiological studies evaluating the potential association between the methylenetetrahydrofolate reductase (MTHFR) A1298C polymorphism and the risk of male infertility. However, the results obtained were inconsistent. Therefore, we performed a meta-analysis to further examine the association between the MTHFR A1298C polymorphism and male infertility. A comprehensive search was conducted to identify all eligible studies from the online literature databases published prior to January 15th, 2016. A total of 20 studies with 4293 cases and 4507 controls were included. An odds ratio (OR) and a 95% confidence interval (95% CI) were calculated to assess the strength of the association. A cumulative meta-analysis, sensitivity analysis and assessment of the publication bias were also performed in this study. The results showed that in the overall analysis, the association between the MTHFR A1298C polymorphism and male infertility was not significant. A stratified analysis by ethnicity revealed a significant increase in the risk of male infertility in the Asian population with the MTHFR A1298C polymorphism (especially in the heterozygote model: OR=1.20, 95% CI=1.01–1.44, P=0.994; the dominant model: OR=1.23, 95% CI=1.04–1.45, P=0.996; and the allele model: OR=1.20, 95% CI=1.04–1.39, P=0.985) but not in the Caucasian population. In the stratified analyses, no significant association was observed between the different types of male infertility. This meta-analysis suggests the MTHFR A1298C polymorphism may be a potential risk factor for male infertility, especially in the Asian population.

Numerous epidemiological studies have studied the association of adiponectin (ADIPOQ) gene and adiponectin receptor (ADIPOR) gene polymorphisms with risk of colorectal cancer (CRC), but the outcomes were incomplete and inconsistent. Therefore, we conducted a meta-analysis to assess the associations systematically. All eligible case-control studies published up to Jan. 2015 were searched from PubMed, the Cochrane library, Elsevier, Wiley Online library, China National Knowledge Infrastructure, WanFang data and Chongqing VIP. Effect sizes of odds ratio (OR) and 95% confidence interval (95%CI) were calculated by using a fixed- or random-effect model. Twelve case-control studies including 6141 cases and 7398 controls were selected. Significant differences in the distributions of allele frequency with CRC risk were directly present in ADIPOQ variants rs2241766, rs1501299 and ADIPOR variant rs1342387. In stratified analysis for different populations, significant differences were present in ADIPOQ variant rs822396 for Ashkenazi Jewish, in ADIPOQ variant rs1501299 and ADIPOR variant rs1342387 for Chinese and in ADIPOQ variant rs 2241766 for Ashkenazi Jewish and Chinese. In addition, the factors correlated with insulin resistance had synergistic effect with ADIPOQ variants rs2241766 T/G and rs1501299 G/T on risk of CRC. ADIPOQ variants rs2241766 T/G, rs1501299 G/T and ADIPOR variant ADIPOR rs1342387 G/A had a population specific correlation with CRC risk, which may be mediated by insulin resistance. And large well-designed studies are still needed for further evaluation of rs822396 and rs1063538, especially for their interaction and combined effect in the correlation with CRC risk.

The systematic treatment based on gemcitabine plus cisplatin is recommended as the current standard chemotherapy for unresectable or metastatic biliary tract cancers. However, the exact benefits from the recognized regime are still dismal. We thus elicit this study in an attempt to analyze whether targeted therapy coupled with various chemotherapy could produce improvement of survival benefits. The clinical trials were searched electronically from databases till July 2016 published in English and Chinese. Nine hundred and sixty-four patients from 7 trials were identified in our analysis. The overall analysis achieved a significantly higher overall response rate (ORR) among the patients treated with targeted drugs plus chemotherapy than chemotherapy alone (OR=1.87; 95% CI: 1.37–2.57; P=0.000), but failed in the overall progression-free survival (PFS) [mean difference (MD)=0.63; 95% CI:–0.45–1.72; P=0.26] and overall survival (OS) (MD=–0.67; 95% CI:–2.54–1.20; P=0.49). In the sub analysis, better ORR was obtained with the addition of EGFR (OR=1.75; 95% CI: 1.20–2.56; P=0.004) and VEGFR (OR=2.5; 95% CI: 1.28–4.87; P=0.007) targeted therapy. Furthermore, the sub analysis of EGFR target showed an significant improvement on PFS (MD=1.36; 95% CI: 0.29–2.43; P=0.01). No significant differences were observed in the incidences of neutropenia (OR=1.37; 95% CI: 0.89–2.12), thrombocytopenia (OR=1.40; 95% CI: 0.83–2.39), anemia (OR=1.21; 95% CI: 0.62–2.38), peripheral neuropathy (OR=1.52; 95% CI: 0.81–2.88), increased AST/ALT (OR=1.40; 95% CI: 0.82–2.39) as well as fatigue (OR=1.65; 95% CI: 0.96–2.84) in either of the treatment groups. In conclusion, better ORR associated with chemotherapy combined with targeted therapy (both targeting EGFR and VEGF) is found in the present meta-analysis without the cost of increased unacceptable toxicities, but regretfully not for the OS. The sub-analysis of targeting EGFR instead of VEGF obtains a superior PFS. Otherwise, there is no statistically significant difference in the overall PFS between the combination regime and chemotherapy alone. Given the paucity of favorable data, we need further studies to characterize optimal targeted agents to confirm the potential value to biliary tract cancer.

Increasing studies have demonstrated that interferon gamma (IFN-γ), which serves as a critical inflammatory cytokine, is essential to induce the immunosuppressive effects of mesenchymal stem cells (MSCs). However, the mechanisms underlying the enhanced immunosuppressive effects of IFN-γ-stimulated MSCs (γMSCs) are not fully understood. MSC-derived microvesicles (MSC-MVs) have been viewed as potential pivotal mediators of the immunosuppressive effects of MSCs. Moreover, microRNAs (miRNAs) are important regulators of immunological processes and can be shuttled from cell to cell by MVs. The aim of our study was to analyze the the miRNA expression signature of MVs derived from γMSCs (γMSC-MVs), which may provide better understanding of the immunosuppressive property of their parent cells. Through miRNA microarray and bioinformatics analysis, we found 62 significantly differentially expressed miRNAs (DEMs) in γMSC-MVs compared with MSC-MVs. And the potential target genes and signaling pathways regulated by DEMs were predicted and analyzed. Interestingly, many DEMs and predicted signaling pathways had been demonstrated to be involved in immunoregulation. Furthermore, the network between immunoregulation-related pathways and relevant DEMs was constructed. Collectively, our research on the miRNA repertoires of γMSC-MVs not only provides new perspectives into the mechanisms underlying the enhanced immunosuppressive property of γMSCs, but also paves the way to clinical application of these potent organelles in the future.

The endothelial-to-mesenchymal transition (EndMT) in endothelial cells contributes to the development of cardiac fibrosis, ultimately leading to cardiac remodeling. In this study, the effects and molecular mechanisms of celastrol (CEL) on transforming growth factor-β1 (TGF-β1)-induced EndMT in human umbilical vein endothelial (HUVEC-12) cells were investigated. The presented data demonstrated that CEL significantly blocked the morphology change of HUVEC-12 cells induced by TGF-β1 without cell cytotoxicity. In accordance with these findings, CEL blocked TGF-β1-induced EndMT as evidenced by the inhibition of the mesenchymal markers, including collagen I, III, α-SMA, fibronectin mRNA expression, and the increase in the mRNA expression of endothelial cell marker CD31. These changes were also confirmed by double immunofluorescence staining of CD31 and vimentin. The in vitro scratch assay showed that CEL inhibited the migration capacity of the transitioned endothelial cells induced by TGF-β1. Further experiments showed that the beneficial effect of CEL on blocking the EndMT in HUVEC-12 cells was associated with the suppression of the TGF-β1/Smads signalling pathway, which was also confirmed by the inhibition of its downstream transcription factor snail1, twist1, twist2, ZEB1 and ZEB2. These results indicate that CEL blocks TGF-β1-induced EndMT through TGF-β1/Smads signalling pathway and suggest that it may be a feasible therapy for cardiac fibrosis diseases.

The dynamic expression of cytokines and phenotypes during the differentiation process of dendritic cell precursors (pre-DCs) to mature dendritic cells (DCs) was investigated, and the effects of inflammatory stimulation with lipopolysaccharide (LPS) on DCs differentiation were understood. The differentiation of bone marrow cells isolated from Balb/c mice was induced to DCs in an 8-day cell culture system with RPMI-1640 complete culture medium containing 10% FBS, 20 ng/mL recombinant mouse granulocyte-macrophage colony-stimulating factor (rmGM-CSF) and 10 ng/mL recombinant mouse interleukin-4 (rmIL-4). On the day 3, 6 and 7 after culture, DCs were divided into non-LPS group and LPS group, given 500 ng/mL LPS for 24 h stimulation and no stimulation respectively. The expression levels of CD11c⁺, MHC-II⁺, CD40⁺, CD80⁺ and CD86⁺ were detected by flow cytometry, and those of IL-2, IL-4, IL-10, IL-12 p70 and IFN-γ in the supernatant by ELISA. On the day 3 and 6 after culture, the expression of IL-2, IL-4, IL-10 and IFN-γ in DCs showed no significant differences between non-LPS group and LPS group, whereas the differences were significant at day 7. The expression levels of cytokines (for IL-2, IL-4, IL-10, IFN-γ and IL-12 p70: 152.86±6.91, 778.33±8.35, 44.55±2.54, 58.26±1.09 and 2423.00±57.21 pg/mL respectively) in LPS group were higher than those in non-LPS group, especially IL-12 p70 increased obviously at day 7. It was concluded that during the differentiation process of pre-DCs to mature DCs, LPS stimulates DCs producing large amounts of IL-12 p70 and Th1-type cytokines as compared with Th2-type cytokines, and day 7 may be a key time-point for DCs polarization.

Essential hypertension (EH) is affected by both genetic and environmental factors. The polymorphism of connexin (Cx) genes is found associated with the development of hypertension. However, the association of the polymorphism of Cxs with EH has not been investigated. This study aimed to investigate the association of the polymorphism of connexin (Cx) genes Cx37, Cx40, and Cx43 with EH in Kazak and Han Chinese in Xinjiang, China. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) were used to analyze the polymorphism of Cx genes in Kazak and Han EH patients as well as their normotensive controls. The results showed that there were no significant differences in the frequencies of different three genotypes (A/A, A/G, and G/G) and A and G alleles of Cx40 rs35594137 and rs11552588 between EH patients and normotensive controls. However, in Kazak EH patients, the frequencies of three genotypes (A/A, A/G, and G/G) of Cx37 rs1630310 were 24.8%, 47.2% and 28.0%, respectively, which were significantly different from those in Han EH patients. In Han EH patients, the frequencies of the three genotypes (C/C, C/G and G/G) of Cx43 rs1925223 were 6.4%, 35.6% and 58.0%, respectively. Frequencies of the other four genotypes had no statistical differences among Kazak and Han EH patients and their normotensive controls. These results suggest polymorphisms of Cx37 rs1630310 and Cx43 rs1925223 genes may be associated with the pathogenesis of EH. Carrying Cx37 rs1630310-A or Cx43 rs1925223-G genotypes may protect against the development of EH.

Gliclazide used for the treatment of type 2 diabetes mellitus (T2DM) stimulates insulin secretion and influences peripheral blood monocytes. The roles of gliclazide in peripheral monocytes of newly diagnosed T2DM patients were investigated in this study. A total of 105 newly diagnosed T2DM patients with no history of antihyperglycemic medication were treated with gliclazide-modified release for 16 weeks. The total and differential leukocyte profiles of peripheral blood were measured at baseline and week 16. The peripheral blood monocyte count at week 16 was significantly lower than that at baseline (P=0.019). Peripheral monocytes level at baseline was positively correlated with waist circumference. After gliclazide treatment, the peripheral monocytes were decreased [(320.09±15.13)×10⁶/L vs. (294.19±14.22)×10⁶/L] in non-abdominal obesity group, but increased in abdominal obesity group [(344.36±17.24)×10⁶/L vs. (351.87±16.93)×10⁶/L]. Compared with non-abdominal obese patients, abdominal obese patients showed higher Δmonocytes (P=0.046) and Δacute insulin secretion (P=0.049), but lower ΔHbA1c (P=0.047). There was significantly positive correlation between Δmonocytes and Δacute insulin secretion (P=0.015), which disappeared after adjusting for age, waist circumference and dosage at baseline. In conclusion, waist circumference is correlated with peripheral monocyte change after gliclazide treatment in Chinese newly diagnosed T2DM patients. Peripheral monocytes are decreased in non-abdominal obesity group and increased in abdominal obesity group after gliclazide treatment.

This study investigated the abnormal expression of ATP synthase β-subunit (ATPsyn-β) in pancreas islets of rat model of polycystic ovary syndrome (PCOS) with type 2 diabetes mellitus (T2DM), and the secretion function changes after up-regulation of ATP5b. Sixty female SD rats were divided into three groups randomly and equally. The rat model of PCOS with T2DM was established by free access to the high-carbohydrate/high-fat diet, subcutaneous injections of DHEA, and a single injection of streptozotocin. The pancreas was removed for the detection of the ATPsyn-β expression by immunohistochemical staining, Western blotting and reverse transcription-PCR (RT-PCR). The pancreas islets of the rats were cultured, isolated with collagenase V and purified by gradient centrifugation, and the insulin secretion after treatment with different glucose concentrations was tested. Lentivirus ATP5b was successfully constructed with the vector of GV208 and transfected into the pancreas islets for the over-expression of ATPsyn-β. The insulin secretion and intracellular ATP content were determined after transfection of the PCOS-T2DM pancreas islets with Lenti-ATP5b. The results showed that the expression of ATPsyn-β protein and mRNA was significantly decreased in the pancreas of PCOS-T2DM rats. The ATP content in the pancreas islets was greatly increased and the insulin secretion was improved after the up-regulation of ATPsyn-β in the pancreas islets transfected with lenti-ATP5b. These results indicated that for PCOS, the ATPsyn-β might be one of the key factors for the attack of T2DM.

Fibronectin containing extra domain A (EDA⁺ FN), a functional glycoprotein participating in several cellular processes, correlates with chronic liver disease. Herein, we aim to investigate the expression and secretion of EDA⁺ FN from hepatocytes in nonalcoholic fatty liver disease (NAFLD) and the underlying mechanisms. Circulating levels of EDA⁺ FN were determined by ELISA in clinical samples. Western blotting and flow cytometry were performed on L02 and HepG2 cell lines to analyze whether the levels of EDA⁺ FN were associated with endoplasmic reticulum (ER) stress-related cell death. Circulating levels of EDA⁺ FN in NAFLD patients were significantly higher than those in control subjects, and positively related with severity of ultrasonographic steatosis score. In cultured hepatocytes, palmitate up-regulated the expression of EDA⁺ FN in a dose-dependent manner. Conversely, when the cells were pretreated with 4-phenylbutyrate, a specific inhibitor of ER stress, up-regulation of EDA⁺ FN could be abrogated. Moreover, silencing CHOP by shRNA enhanced the release of EDA⁺ FN from hepatocytes following palmitate treatment, which was involved in ER stress-related cell damage. These findings suggest that the up-regulated level of EDA⁺ FN is associated with liver damage in NAFLD, and ER stress-mediated cell damage contributes to the release of EDA⁺ FN from hepatocytes.

Simvastatin is a hypolipidemic drug that inhibits hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase to control elevated cholesterol, or hypercholesterolemia. Previous studies have shown that simvastatin may attenuate inflammation in ischemia-reperfusion injury and sepsis. Herein, we hypothesized that simvastatin may prevent rats from lipopolysaccharide (LPS)-induced septic shock. In our study, rats were divided into a saline group, an LPS group and an LPS plus simvastatin group. Male Sprague-Dawley (SD) rats were pretreated with simvastatin (1 mg/kg) for 30 min before the addition of LPS (8 mg/kg), with variations in left ventricular pressure recorded throughout. Ninety min after LPS injection, whole blood was collected from the inferior vena cava, and neutrophils were separated from the whole blood using separating medium. The neutrophils were then lysed for Western blotting to detect the levels of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1). In addition, mesentery microcirculations of inlet diameter, outlet diameter and blood flow rate were measured in all three groups. The results indicated that simvastatin significantly promoted heart systolic function and increased the level of uPA while simultaneously inhibited the expression of PAI-1 as compared with LPS group. Moreover, simvastatin reversed the LPS-induced inhibition of mesentery microcirculation. Taken together, it was suggested that simvastatin can effectively protect the rats from LPS-induced septic shock.

Relapse and metastasis are frequent in colon cancer and may be linked to stem cell characteristics. This study isolated side population (SP) cells from a colon cancer cell line (Colo-320) and examined their self-renewal and differentiation abilities. Compared to non-SP (NSP) cells, SP colon cancer cells were more tumorigenic in vivo and exhibited more invasive characteristics and a greater ability to form colonies. Additionally, more cells were in G₀/G₁ phase and more highly expressed the multidrug resistance protein BCRP/ABCG2. We achieved enhanced chemotherapy sensitivity by transfecting SP cells with a hairpin-like, small interfering RNA (siRNA) eukaryotic expression plasmid targeting BCRP/ABCG2.

To study maternal and perinatal outcomes after cervical cerclage in both singleton and twin pregnancies, we retrospectively reviewed women undergoing cervical cerclage for cervical insufficiency at Tongji Hospital, Wuhan, China from January 1, 2010 to July 31, 2015 to evaluate primary and secondary outcomes for subgroups with cervical length (CL) ≤15, >15 to <25, and ≥25 mm. Of 166 patients who underwent cervical cerclage, after exclusion of patients with missed abortion and continuing pregnancy, 141 patients (121 singleton and 20 twin pregnancies) were included in the analysis. Mean gestational age at birth was 34.22 and 28.27 weeks for singleton and twin pregnancies, respectively. There were 17 (14.05%) and 13 (33.33%) neonatal deaths in singleton and twin pregnancies, respectively. Mean age (31.60±4.62 vs. 31.22±4.63 years, P=0.39) and gestational weeks at cerclage (18.50±4.62 vs. 19.31±4.99, P=0.47) were similar for both groups. Mean gestational weeks at delivery (34.22±5.77 vs. 28.27±6.17, P<0.001) and the suture to delivery interval (15.72±7.15 vs. 8.96±6.70, P<0.001) were significantly longer in the singleton group. These variables indicate a linear negative correlation with the degree of CL shortening, with better outcomes in patients with CL ≥25 mm who underwent cerclage, both in singleton and twin pregnancies. No difference in mode of delivery existed between the singleton group and twin group. Our results indicate a high risk of preterm delivery in both groups, especially in the twin group. Patients with a history of preterm labor and CL >25 mm in the current pregnancy, possibly in a twin pregnancy, could benefit from elective cervical cerclage; however, cervical cerclage was inadvisable for twin pregnancies with a CL >15 and <25 mm. Our data emphasize the importance of re-evaluating the efficacy of cervical cerclage for twin pregnancies in well-designed clinical trials.

Soluble receptor for advanced glycation end products (sRAGE) can decoy the toxic AGEs and is considered to be a protective factor. This study aimed to evaluate the correlation between intrafollicular sRAGE levels and clinical outcomes in infertile women of young or advanced maternal age (AMA) undergoing in vitro fertilization (IVF). A total of 62 young women and 62 AMA women who would undergo IVF were included in this prospective study. The intrafollicular sRAGE concentration was measured to determine its association with the number of retrieved oocytes, fertilized oocytes, high-quality embryos or achievement of clinical pregnancy in young and AMA women, respectively. Besides, correlations between sRAGE and age or follicle-stimulating hormone (FSH) were examined. We found that the intrafollicular sRAGE levels were higher in young patients than those in AMA patients, suggesting that the sRAGE levels were inversely correlated with age. In young patients, sRAGE showed no correlation with the number of retrieved oocytes, fertilized oocytes, high-quality embryos or achievement of clinical pregnancy. But it was found that AMA patients with more retrieved oocytes, fertilized oocytes and high-quality embryos demonstrated higher sRAGE levels, which were a prognostic factor for getting clinical pregnancy independent of age or FSH level. In conclusion, the sRAGE levels decrease with age. Elevated intrafollicular sRAGE levels indicate good follicular growth, fertilization and embryonic development, and successful clinical pregnancy in AMA women, while in young women, the role of sRAGE may not be so predominant.

Spontaneous cervical epidural hematoms (SCEH) complicated with mild cervical spondylotic myelopathy (CSM) is a rare but emerging condition. Early diagnosis and treatment are important for good outcomes. This study aimed to investigate the clinical characteristics of this condition and to discuss the optimal treatment. The clinical data from 8 patients with SCEH plus CSM who were divided into two groups by treatment methods were retrospectively analyzed. The neurological function of the patients was assessed by Japanese Orthopedic Association (JOA) score before and after the surgical operations. Other factors were reviewed with medical records. Among them, 4 out of the 8 patients underwent emergency surgery, and the rest 3 patients experienced an initial conservative treatment and ultimately received a laminectomy. We found that the Frankel Scale scores in most of the surgical patients were increased after surgery (6/7, 85.7%). However, the JOA scores at the 6th month after onset were even lower than those before onset in 3 of the operative cases, and those in the patients who were given conservative treatment showed no significant change. It was concluded that some patients with SCEH and CSM treated with a timely operation may obtain relief from their previous CSM symptoms. However, the final neurological deficits of these patients were closely related to the progressive interval which refers to the hours between the initial onset and the occurrence of new neurological deficits or mild CSM deterioration, no matter whether they accept the operation. We found the crucial progressive interval may be in 9 h. Early MRI and prompt neurosurgical intervention are also important to improve the neurological deficits.

The applied value of serum hepcidin in differential diagnosis of infection fevers versus tumor fevers was explored. A total of 432 fever patients were selected according to the domestic fever of unknown origin (FUO) diagnostic criteria from our hospital between June 2010 and November 2013. Venous blood samples were taken on the day 1, 5, 10 after admission. The infection group (98 cases) and the tumor group (50 cases) were set up based on the clinical and laboratory findings. ELISA was used to determine the serum hepcidin and IL-6 levels. SPSS 13.0 was used for statistical analysis. Hepcidin showed obvious descending trend on the 10th day in both the bacterial infection group (66 cases) and the virus infection group (32 cases), and the descending trend was similar to that of inflammatory indexes such as procalcitonin (PCT), hypersensitive C-reactive protein (h-CRP), erythrocyte sedimentation rate (ESR), white blood cell (WBC), and ferritin. Serum hepcidin showed no obvious differences in the tumor group on the day 1, 5, 10 after admission. In the infection groups, serum hepcidin was positively correlated with IL-6 (r=0.687, P=0.000) and CRP (r=0.487, P=0.026), but had a poor correlation with blood sedimentation, ferritin, PCT and WBC (P>0.05). Monitoring dynamic changes of hepcidin and related inflammatory factors in patients with fever is expected to be used for clinical identification of infection fever and tumor fever.

In order to discover the risk factors for 30-day mortality in bloodstream infections (BSI) caused by Enterococcus spp. strains, we explored the clinical and therapeutic profile of patients with Enterococcus spp. BSI and the characteristics of this condition. A total of 64 patients with BSI caused by Enterococcus spp. who were treated in our hospital between 2006 and 2015 were included in the study. The clinical features of patients, microbiology, and 30-day mortality were collected from the electronic medical records database and analyzed. The results showed that there were 38 patients infected by Enterococcus faecalis (E. faecalis), 24 by Enterococcus faecium (E. faecium), 1 by Enterococcus casseliflavus (E. casseliflavus), and 1 by Enterococcus gallinarum (E. gallinarum). A Charlson comorbidity score ≥5, corticosteroid treatment, placement of catheters or other prosthetic devices and history of antibiotic use were found more frequently in E. faecium BSI patients than in E. faecalis patients (P=0.017, P=0.027, P=0.008 and P=0.027, respectively). Furthermore, the univariate and multivariate analysis showed that corticosteroid treatment (OR=17.385, P=0.008), hospital acquisition (OR=16.328, P=0.038), and vascular catheter infection (OR=14.788, P=0.025) were all independently associated with 30-day mortality. Our results indicate that E. faecalis and E. faecium are two different pathogens with unique microbiologic characteristics, which cause different clinical features in BSI, and the empiric antimicrobial treatments are paramount for patients with enterococcal BSI.

This study investigated the relationship among the severity of hearing impairment, vestibular function and balance function in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). A total of 35 ISSNHL patients (including 21 patients with vertigo) were enrolled. All of the patients underwent audiometry, sensory organization test (SOT), caloric test, cervical vestibular-evoked myogenic potential (cVEMP) test and ocular vestibular-evoked myogenic potential (oVEMP) test. Significant relationship was found between vertigo and hearing loss grade (P=0.009), and between SOT VEST grade and hearing loss grade (P=0.001). The abnormal rate of oVEMP test was the highest, followed by the abnormal rates of caloric and cVEMP tests, not only in patients with vertigo but also in those without vertigo. The vestibular end organs were more susceptible to damage in patients with vertigo (compared with patients without vertigo). Significant relationship was found between presence of vertigo and SOT VEST grade (P=0.010). We demonstrated that vestibular end organs may be impaired not only in patients with vertigo but also in patients without vertigo. The cochlear and vestibular impairment could be more serious in patients with vertigo than in those without vertigo. Vertigo does not necessarily bear a causal relationship with the impairment of the vestibular end organs. SOT VEST grade could be used to reflect the presence of vertigo state in the ISSNHL patients. Apart from audiometry, the function of peripheral vestibular end organs and balance function should be evaluated to comprehensively understand ISSNHL. Better assessment of the condition will help us in clinical diagnosis, treatment and prognosis evaluation of ISSNHL.

The aim of the present study was to investigate the effect of “nourishing liver and kidney” acupuncture therapy on motor and cognitive deficits, and the underlying mechanism following cerebral ischemia-reperfusion (I/R) via increasing the expression of brain derived neurotrophic factor (BDNF) and synaptophysin (SYN) in the hippocampus. Healthy adult male SD rats were randomly divided into sham operation group (n=51), model group (n=51), acupuncture group (n=51) and acupuncture control group (n=51). The middle cerebral I/R model was established. Acupunctures were performed in the acupuncture group and acupuncture control group at acupoints of Taixi (K103), Taichong (ST09) of both sides, for 30 min once daily every morning. The animals in the sham operation group and model group were conventionally fed in the cage, without any intervention therapy. The rats of each group were assessed with modified neurological severity scores (mNSS). The expression of BDNF and SYN in the hippocampus was detected by immunohistochemical SP method and the synaptic structure in hippocampus area was assessed morphologically and quantitatively at the 3rd, 7th and 14th day. The Morris water Maze (MWM) test was used to evaluate the rats’ learning and memory abilities on the 15th day after acupuncture. The animals in the acupuncture control group and sham operation group presented no neurological deficit. In the acupuncture group, the nerve functional recovery was significantly better than that in the model group at the 7th and 14th day after modeling. The average MWM escape latency in the acupuncture group was shorter than that in the model group at the 3rd, 4th and 5th day. The number of crossings of the platform quadrant in the acupuncture group was significantly more than that in the model group. At the each time point, the expression levels of BDNF and SYN in the hippocampal regions increased significantly in the model group as compared with the sham operation group and the acupuncture control group. In the acupuncture group, the expression levels of BDNF at the 7th and 14th day increased more significantly than those in the model group. In the acupuncture group, the expression levels of SYN at the each time point increased more significantly than those in the model group. The post-synaptic density (PSD) was significantly increased and the synapse cleft width was narrowed in the acupuncture group as compared with other groups. The synaptic curvatures were improved obviously in the acupuncture group in contrast to the model group. It was concluded that the “nourishing liver and kidney” acupuncture therapy has positive effects on behavioral recovery, as well as learning and memory abilities, probably by promoting the expression of BDNF and SYN, and synaptic structure reconstruction in the ipsilateral hippocampus after I/R in rats. The “nourishing liver and kidney” acupuncture therapy can promote the functional recovery in rats after cerebral ischemia injury.

The most effective sequence of small interfering RNA (siRNA) silencing STAT3 of psoriatic keratinocytes (KCs) was screened out, and the effects of the most effective siRNA combined with ultrasonic irradiation and SonoVue microbubbles on the expression of STAT3 of KCs and the dose- and time-response were investigated. Three chemically-synthetic siRNAs targeting STAT3 carried by Lipofectamine 3000 were transfected into KCs, and the effects on STAT3 expression were detected, then the most effective siRNA was selected for the subsequent experiments. The negative controls of siRNA (siRNA-NC) labeled with Cy3 carried by Lipofectamine 3000 combined with ultrasonic irradiation and SonoVue microbubbles were transfected into KCs, then the optimal parameters of ultrasonic irradiation were determined. The most effective siRNA carried by Li-pofectamine 3000 combined with ultrasonic irradiation at the optimal parameters and SonoVue microbubbles was transfected into KCs, and the dose- and time-response of RNA interference was determined. The effect of RNA interference by the most effective siRNA at the optimal time and dose carried by Lipofectamine 3000 combined with ultrasonic irradiation and SonoVue microbubbles (LUS group) was compared with that only carried by Li-pofectamine 3000 (L group). The results showed that siRNA-3 achieved the highest silencing efficacy. 0.5 W/cm2 and 30 s were selected as the parameters of ultrasonic irradiation. The siRNA-3 carried by Lipofectamine 3000 combined with ultrasonic irradiation and SonoVue microbubbles could effectively knock down the STAT3 expression at mRNA and protein levels in dose- and time-dependent manners determined at 100 nmol/L with maximum downregulation on mRNA at 48 h, and on protein at 72 h after transfection. The LUS group achieved the highest silencing efficacy. It was concluded that siRNA-3 carried by Lipofectamine 3000 combined with ultrasonic irradiation and SonoVue microbubbles could effectively knock down the STAT3 expression in psoriatic KCs, and the optimized transfection condition and the sequence of siRNA-3 could serve for further research on gene therapy of psoriasis.

Low birth weight (LBW) and preterm birth (PB) are associated with newborn mortality and diseases in adulthood. We explored factors related to LBW and PB by conducting a population-based case-control study from January 2011 to December 2013 in Wuhan, China. A total of 337 LBW newborn babies, 472 PB babies, and 708 babies with normal birth weights and born from term pregnancies were included in this study. Information of newborns and their parents was collected by trained investigators using questionnaires and referring to medical records. Univariate and logistic regression analyses with the stepwise selection method were used to determine the associations of related factors with LBW and PB. Results showed that maternal hypertension (OR=6.78, 95% CI: 2.27–20.29, P=0.001), maternal high-risk pregnancy (OR=1.53, 95% CI: 1.06–2.21, P=0.022), and maternal fruit intake ≥300 g per day during the first trimester (OR=1.70, 95% CI: 1.17–2.45, P=0.005) were associated with LBW. BMI ≥24 kg/m² of mother prior to delivery (OR=0.48, 95% CI: 0.32–0.74, P=0.001) and gestation ≥37 weeks (OR=0.01, 95% CI: 0.00–0.02, P<0.034) were protective factors for LBW. Maternal hypertension (OR=3.36, 95% CI: 1.26–8.98, P=0.016), maternal high-risk pregnancy (OR=4.38, 95% CI: 3.26–5.88, P<0.001), maternal meal intake of only twice per day (OR=1.88, 95% CI: 1.10–3.20, P=0.021), and mother liking food with lots of aginomoto and salt (OR=1.60, 95% CI: 1.02–2.51, P=0.040) were risk factors for PB. BMI ≥24 kg/m² of mother prior to delivery (OR=0.66, 95% CI: 0.47–0.93, P=0.018), distance of house from road ≥36 meters (OR=0.72, 95% CI: 0.53–0.97, P=0.028), and living in rural area (OR= 0.60, 95% CI: 0.37–0.99, P=0.047) were protective factors for PB. Our study demonstrated some risk factors and protective factors for LBW and PB, and provided valuable information for the prevention of the conditions among newborns.

Andrographolide total ester sulfonate (ATES) injection is one of the products of traditional Chinese medicine (TCM) currently used against viral infection in China. ATES injection was approved for manufacturing and marketing in January 2002. It is indicated for acute respiratory infections, tonsillitis, chronic obstructive pulmonary disease, influenza, foot and mouth disease, bronchiolitis, herpangina, mumps, infectious mononucleosis and psychosis. However, its usage also carries risk. We investigated the use of ATES at the Wuhan Union Hospital from January 2014 to December 2014 and evaluated its real-world clinical application using the hospital centralized monitoring method. A total of 848 cases were enrolled in this study. In these cases, it was mainly used for postoperative anti-inflammation and treating upper respiratory infection, pneumonia and bronchitis. Among them, 39.86% were contraindicated. Irregular medication of adults and children accounted for 1.91% and 23.38%, respectively. Improper choice of solvent accounted for 3.18%. The choice of intravenous drip versus aerosol inhalation was reasonable. A case of adverse events (AEs) was observed in the monitoring period, and the incidence of adverse drug reaction (ADR) of ATES injection was 0.12%. ATES injection in our hospital is relatively safe with a low incidence of adverse reactions. The study assesses the clinical usage and adverse reactions of ATES injection, and provides suggestions for rational use in clinical practice.

The three-dimensional visualization model of human body duct is based on virtual anatomical structure reconstruction with duct angiography, which realizes virtual model transferred from two-dimensional, planar and static images into three-dimensional, stereoscopic and dynamic ones repectively. In recent years, the multi-duct segmentation and division of the same specimen (or organ) is the focus of attention shared by surgeons and clinical anatomists. On the basis of 4.22 g/cm³ body bone density, this study has screened out metal oxide contract agent with different density for infusion and modeling, as well as compared and analyzed the effects of three-dimensional image of CT virtual bronchoscopy (CTVB), three-dimensional image of CT maximum intensity projection and three-dimensional model. This experiment result showed synchronously infusing multi-duct of same specimen (or organ) with contrast agent in different densities could reconstruct three-dimensional models of all ducts once only and adjust threshold to develop single or multiple ducts. It was easier to segment and observe the duct structure, anastomosis, directions and crossing in different parts, which was beyond comparison with three-dimensional image of CTVB. Although the existing three-dimensional duct reconstruction techniques still cannot be applied in living bodies temporarily, this study focused on a creative design of ducts segmentation in different density, which proposed a new experimental idea for developing multi-duct three-dimensional model in living body in the future. It will play a significant role in disease diagnosis and individual design in surgical treatment program. Therefore, this study observes the three-dimensional status of human duct with the application of contrast agent fillers in different density, combined with three-dimensional reconstruction technology. It provides an innovative idea and method for constructing three-dimensional model of digital multi-duct specimen, and the ultimate goal is to develop the digitized virtual human and precise medical treatment better and faster.