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Esophageal squamous cell carcinoma (ESCC) is a highly malignant gastrointestinal cancer with a high recurrence rate and poor prognosis. Although N6-methyladenosine (m6A), the most abundant epitranscriptomic modification of mRNAs, has been implicated in several cancers, little is known about its participation in ESCC progression. We found reduced expression of ALKBH5, an m6A demethylase, in ESCC tissue specimens with a more pronounced effect in T3-T4, N1-N3, clinical stages III-IV, and histological grade III tumors, suggesting its involvement in advanced stages of ESCC. Exogenous expression of ALKBH5 inhibited the in vitro proliferation of ESCC cells, whereas depletion of endogenous ALKBH5 markedly enhanced ESCC cell proliferation in vitro. This suggests ALKBH5 exerts anti-proliferative effects on ESCC growth. Furthermore, ALKBH5 overexpression suppressed tumor growth of Eca-109 cells in nude mice; conversely, depletion of endogenous ALKBH5 accelerated tumor growth of TE-13 cells in vivo. The growth-inhibitory effects of ALKBH5 overexpression are partly attributed to a G1-phase arrest. In addition, ALKBH5 overexpression reduced the in vitro migration and invasion of ESCC cells. Altogether, our findings demonstrate that the loss of ALKBH5 expression contributes to ESCC malignancy.

To evaluate the recovery of early urinary continence in patients with prostate cancer using a suprapubic catheter during Retzius-sparing robotic-assistant laparoscopic prostatectomy. From January 2018 to January 2019, 223 patients diagnosed with prostate cancer who underwent Retzius-sparing robotic-assistant laparoscopic prostatectomy in Diakonie Klinikum Stuttgart were involved in our study. From January 2018 to June 2018, patients (112 cases) only had an indwelling urinary catheter during Retzius-sparing robotic-assistant laparoscopic prostatectomy, while from July 2018 to January 2019, patients (111 cases) were offered an extra suprapubic catheter during operation. The recovery of early urinary continence of patients was mainly investigated one month later. The overall early urinary continence rate was 81.61%. Patients with suprapubic catheter had better urinary control results, compared to patients with only indwelling urinary catheter (87.39% vs 75.89%, p = 0.027). In addition, International Prostate Symptom Score and irritative subscore in patients with good urinary control were significantly lower than that in patients with urinary incontinence. Suprapubic catheter insertion (OR 0.395; 95% CI 0.190–0.821) and advanced pathological tumor stage (T3a–T4) (OR 2.061; 95% CI 1.008–4.217) were two independent influencing factors for early urinary continence recovery in patients who underwent Retzius-sparing robotic-assistant laparoscopic prostatectomy through multivariate logistic regression analysis. Suprapubic catheter insertion may be helpful for early urinary continence recovery in patients with Retzius-sparing Robotic-assistant laparoscopic prostatectomy. Advanced pathological tumor stage (T3a–T4) before Retzius-sparing robotic-assistant laparoscopic prostatectomy might be associated with poor urinary control.

Summary Given the lack of defining features in the clinical manifestations and radiographic findings for children with mycoplasma pneumoniae pneumonia (MPP), quantitative polymerase chain reaction (qPCR) has become a useful diagnostic method. This study was performed to explore the relationship between the qPCR findings, clinical symptoms, and inflammatory markers in children with MPP. Four hundred children with MPP have been enrolled in this retrospective analysis. All clinical and analytical information, including mycoplasma pneumoniae (MP) PCR results, has been collected. Based on the PCR results, the patients were divided into groups with load values (copy number) < 105 (54 cases), ≥105 and 108 (49 cases). The clinical features (including symptoms and signs) and inflammatory indicators were compared among the groups. The incidence of high fever (above 39°C), thermal peak during the entire hospitalization period, fever duration, days of hospitalization, and plasma lactate dehydrogenase (LDH) levels were statistically correlated with the MP PCR load value in children with MPP. The analysis of relevance degree showed the correlative order as a thermal peak of hospitalization > duration of fever > period of hospitalization > LDH value > C-reactive protein value. The host immune response was significantly greater in the complication group than in the non-complication group.

Aim To reveal a novel MITF gene mutation in Waardenburg syndrome (WS), which is an autosomal dominant inherited neurogenic disorder that consists of various degrees of sensorineural deafness and pigmentary abnormalities in the eyes, hair and skin. Methods The genetic analysis of the Chinese family was conducted by whole-exome sequencing, then the results were confirmed by Sanger sequencing. Results WS is classified into type I to IV, which are identified by the W index, clinical characteristics and additional features. The MITF gene mostly accounts for WS type II. In this study, a de novo heterozygous mutation in the MITF gene, c.638A>G in exon 7, was identified in the patient diagnosed with WS type I features, as the W index was 2.17 (over 2.10), with dystrophia canthorum, congenital bilateral profound hearing loss, bilateral heterochromia irides, premature greying of the hair, and excessive freckling on the face at birth. She also underwent refractive errors and esotropia, reduced pigmentation of the choroid and visible choroid vessels. The mutation was not found in previous studies or mutation databases. Conclusion The novel mutation in the MITF gene, which altered the protein in amino acids 213 from the glutamic acid to glycine, is the genetic pathological cause for WS features in the patient. Those characteristics of this family revealed a novel genetic heterogeneity of MITF in WS, which expanded the database of MITF mutations and offered a possible in correcting the W index value of WS in distinct ethnicities. Moreover, ocular symptoms should be emphasized in all types of WS patients.

Oxidative stress-induced injury and apoptosis of human lens epithelial cells (HLECs) are early events in the development of age-related cataracts (ARCs). Humanin (HN) is a mitochondrial-related peptide that serves a cytoprotective role in various cell types and animal models. Following HN knockdown or overexpression, the level of reactive oxygen species (ROS), mitochondrial membrane potential and mitochondrial DNA copy number, cell viability, LDH activity and apoptosis of HLECs under oxidative stress were detected, and apoptosis and autophagy were detected via transmission electron microscopy. The results suggested that HN may be involved in the response of HLECs to oxidative stress, and that HN expression was significantly upregulated under oxidative stress conditions. Furthermore, exogenous HN reduced intracellular ROS content and mitochondrial damage, and enhanced mitochondrial biosynthesis; however, this protection was lost in an endogenous HN knockdown cell model. In addition, to the best of our knowledge, the present study was the first to identify that HN increased mitochondrial autophagy, which was involved in reducing ROS production under oxidative stress. The present study indicated a potential mechanism underlying the anti-oxidative damage and apoptotic effects of HN under oxidative stress. In conclusion, HN may be a potential therapeutic target for ARCs as it has a significant cellular protective effect on HLECs under oxidative stress; therefore, further study is required to investigate its role in the occurrence and development of ARCs.

The present meta-analysis was conducted to investigate the association between circulating chemerin levels and polycystic ovary syndrome (PCOS) in women.Relevant studies published up to May 2020 were searched from PubMed, Ovid, the Cochrane Library, and Clinical Trial Database. A random effects model was used to measure the strength of association between PCOS and chemerin by using the standardized mean difference (SMD) and 95% confidence interval (CI). All data were analyzed using Stata 12.0 (version 12; Stata-Corp, College Station, TX).The final meta-analysis included eight studies with 15 results including a total of 897 participants (524 patients with PCOS and 373 controls). The circulating chemerin levels were higher in patients with PCOS (random effects SMD = 1.07; 95% CI: 0.55-1.59;Our meta-analysis indicated that women with PCOS have significantly higher circulating chemerin levels than in healthy women, indicating that chemerin may be involved in the pathogenesis of PCOS.

Background: Population-based studies have consistently showed an increased incidence of coronary heart disease and cardiac mortality in patients with type 2 diabetes mellitus (T2DM). Tongmai Jiangtang capsules (TJC) are Chinese patent medicines that have been approved in China for the treatment of diabetic vascular complications. However, the evidence supporting the efficacy of Tongmai Jiangtang capsules in type 2 diabetic coronary heart disease (T2DM-CHD) remains unclear. Herein, we designed a randomized, parallel-controlled clinical trial to investigate a new complementary therapy for T2DM-CHD patients.Methods: A total of 360 T2DM-CHD subjects (aged 18–75 years) will be randomly assigned to the TJC group or the placebo group at a 2:1 ratio. On the basis of western medicine therapy, all the participants will receive TJC or placebo, orally, three capsules/treatment, three per day for 12 weeks. The primary outcomes will be assessed according to the Canadian Cardiovascular Society (CCS) classification. All statistical analyses will be performed setting a two-sided 0.05 significance level, using SAS 9.4 statistical software.Discussion: The efficacy of TJC for the treatment of T2DM-CHD patients will be evaluated. The study will provide reliable clinical research evidence for application of TJC in treating T2DM-CHD patients.Clinical Trial Registration:https://www.chictr.org.cn/enIndex.aspx, Chinese Clinical Trial Registry ChiCTR2000037491.

ObjectiveThe longitudinal risk of colorectal cancer (CRC) associated with subtypes of serrated polyps (SPs) remains incompletely understood.DesignThis community-based, case–control study included 317 178 Kaiser Permanente Northern California members who underwent their first colonoscopy during 2006–2016. Nested within this population, we identified 695 cases of CRC and 3475 CRC-free controls (matched 5:1 to cases for age, sex and year of colonoscopy). Two expert pathologists reviewed the tissue slides of all SPs identified on the first colonoscopy and reclassified them to sessile serrated lesions (SSLs), hyperplastic polyps (HPs) and traditional serrated adenomas. SPs with borderline characteristics of SSLs but insufficient to make a definitive diagnosis were categorised as unspecified SPs. The association with development of CRC was assessed using multivariable logistic regression.ResultsCompared with individuals with no polyp, the adjusted ORs (aORs) for SSL alone or with synchronous adenoma were 2.9 (95% CI: 1.8 to 4.8) and 4.4 (95% CI: 2.7 to 7.2), respectively. The aORs for SSL with dysplasia, large proximal SSL,and small proximal SSL were 10.3 (95% CI: 2.1 to 50.3), 12.8 (95% CI: 3.5 to 46.9) and 1.9 (95% CI: 0.8 to 4.7), respectively. Proximal unspecified SP also conferred an increased risk (aOR: 5.8, 95% CI: 2.2 to 15.2). Women with SSL were associated with higher risk (aOR: 4.4; 95% CI: 2.3 to 8.2) than men (aOR: 1.7; 95% CI: 0.8 to 3.8).ConclusionIncreased risk of CRC was observed in individuals with SSLs, particularly large proximal ones or with dysplasia, supporting close endoscopic surveillance. Proximal unspecified SPs were also associated with increased risk of CRC and should be managed as SSLs.

Emerging evidence suggests that the coupling relating the structural connectivity (SC) of the brain to its functional connectivity (FC) exhibits remarkable changes during development, normal aging, and diseases. Although altered structural-functional connectivity couplings (SC-FC couplings) have been previously reported in schizophrenia patients, the alterations in SC-FC couplings of different illness stages of schizophrenia (SZ) remain largely unknown. In this study, we collected structural and resting-state functional MRI data from 73 normal controls (NCs), 61 first-episode (FeSZ) and 78 chronic (CSZ) schizophrenia patients. Positive and negative syndrome scale (PANSS) scores were assessed for all patients. Structural and functional brain networks were constructed using gray matter volume (GMV) and resting-state magnetic resonance imaging (rs-fMRI) time series measurements. At the connectivity level, the CSZ patients showed significantly increased SC-FC coupling strength compared with the FeSZ patients. At the node strength level, significant decreased SC-FC coupling strength was observed in the FeSZ patients compared to that of the NCs, and the coupling strength was positively correlated with negative PANSS scores. These results demonstrated divergent alterations of SC-FC couplings in FeSZ and CSZ patients. Our findings provide new insight into the neuropathological mechanisms underlying the developmental course of SZ.

A tricationic cage was synthesized via click chemistry. The cage has a preorganized cavity, which is surrounded by six relatively acidic C-H bonds. In organic solvent, the cage can recognize a variety of anions, among which the Cl

Corneal neovascularization (CNV) is one of the leading risk factors for vision loss. Anti-angiogenic drugs can theoretically be extended to the treatment of CNV. However, the application of these drugs is often hindered by traditional administration methods, e.g., eye drops, which is ascribed to the unique structure of the cornea and tear film. In this study, cationic polypeptide nanoparticles with mucoadhesive ability that carry lipophilic cabozantinib (a tyrosine kinase inhibitor), called Cabo-NPs, were developed for sustained cabozantinib release and inhibition of CNV. The polypeptides were synthesized via N-carboxyanhydride ring-opening polymerization and could self-assemble into micelles with cabozantinib in aqueous solution. The Cabo-NPs possessed good biocompatibility both in corneal epithelial cells and mouse corneas. More importantly, in vitro angiogenesis assays demonstrated the strong inhibitory effect of Cabo-NPs on cell migration and tube formation. Furthermore, the Cabo-NPs exerted superior anti-angiogenic effects with remarkable reductions in the neovascular area, which were as effective as the clinical dexamethasone but without apparent side effects. The therapeutic mechanism of the Cabo-NPs is closely related to the significant decrease in proangiogenic and proinflammatory factors, suppressing neovascularization and inflammation. Overall, cationic Cabo-NPs offer a new prospect for safe and effective CNV treatment via enhancing the bioavailability of lipophilic cabozantinib.

Human small intestinal crypts are the source of intestinal stem cells (ISCs) that are capable of undergoing self-renewal and differentiation to an epithelial layer. The development of methods to expand the ISCs has provided opportunities to model human intestinal epithelial disorders. Human crypt samples are usually obtained from either endoscopic or discarded surgical samples, and are thereby exposed to warm ischemia, which may impair their in vitro growth as three-dimensional culture as spheroids or enteroids. In this study we compared duodenal samples obtained from discarded surgical samples to those isolated from whole-body preserved cadaveric donors to generate in vitro cultures. We also examined the effect of storage solution (phosphate-buffered saline or University of Wisconsin [UW] solution) as well as multiple storage times on crypt isolation and growth in culture. We found that intestinal crypts were successfully isolated from cadaveric tissue stored for up to 144 h post-procurement and also were able to generate enteroids and spheroids in certain media conditions. Surgical samples stored in UW after procurement were sufficiently viable up to 24 h and also allowed the generation of enteroids and spheroids. We conclude that surgical samples stored for up to 24 h post-procurement in UW solution allowed for delayed crypt isolation and viable in vitro cultures. Furthermore, in situ, hypothermic preservation in cadaveric duodenal samples permitted crypt/ISC isolation, and successful culture of spheroids and enteroids from tissues held for up to 6 days post-procurement.

PCR amplification of the rrs2 gene indicated that 50% (62/124) of insectivorous bats from eastern China were infected with Leptospira borgpetersenii, L. kirschneri, and several potentially new Leptospira species. Multilocus sequence typing defined 3 novel sequence types in L. kirschneri, suggesting that bats are major carriers of Leptospira.

AIM: To explore the effect of parthenolide on hydrogen peroxide (H2O2)-induced apoptosis in human lens epithelial (HLE) cells. METHODS: The morphology and number of apoptotic HLE cells were assessed using light microscopy and flow cytometry. Cell viability was tested by MTS assay. In addition, the expression of related proteins was measured by Western blot assay. RESULTS: Apoptosis of HLE cells was induced by 200 µmol/L H2O2, and the viability of these cells was similar to the half maximal inhibitory concentration (IC50), as examined by MTS assay. In addition, cells were treated with either different concentrations (6.25, 12.5, 25 and 50 µmol/L) of parthenolide along with 200 µmol/L H2O2 or only 50 µmol/L parthenolide or 200 µmol/L H2O2 for 24h. Following treatment with higher concentrations of parthenolide (50 μmol/L), fewer HLE cells underwent H2O2-induced apoptosis, and cell viability was increased. Further, Western blot assay showed that the parthenolide treatment reduced the expression of caspase-3 and caspase-9, which are considered core apoptotic proteins, and decreased the levels of phosphorylated nuclear factor-κB (NF-κB), ERK1/2 [a member of the mitogen-activated protein kinase (MAPK) family], and Akt proteins in HLE cells. CONCLUSION: Parthenolide may suppress H2O2-induced apoptosis in HLE cells by interfering with NF-κB, MAPKs, and Akt signaling.

Purpose The aim of the study is to investigate the effects of ABCB1 , ABCC2 , UGT2B7 and HNF4α genetic polymorphisms on plasma oxcarbazepine (OXC) concentrations and therapeutic efficacy in Han Chinese patients with epilepsy. Methods We recruited 116 Han Chinese patients with epilepsy who were receiving OXC monotherapy. Blood samples were taken and OXC levels were measured. The polymorphisms of ABCB1 rs1045642, ABCC2 rs2273697, UGT2B7 rs7439366, and HNF4α rs2071197 were determined. The therapeutic efficacy of OXC at the 1-year time-point was assessed. Data analysis was performed using IBM SPSS Statistics 22.0. Results The genetic polymorphism of ABCB1 rs1045642 was found to be associated with normalized OXC concentration and therapeutic efficacy in patients with epilepsy (P UGT2B7 rs7439366, the allele polymorphism exhibited a correlation with treatment outcome, but not OXC concentration. The polymorphisms of ABCC2 rs2273697 and HNF4α rs2071197 was not associated with OXC concentrations and therapeutic efficacy. Conclusion These results suggested that ABCB1 rs1045642 and UGT2B7 rs7439366 may affect OXC pharmacokinetics and therapeutic efficacy in Han Chinese patients with epilepsy. However, further studies in larger populations and other ethnic groups are required.

Neuronal necrosis occurs during early phase of ischemic insult. However, our knowledge of neuronal necrosis is still inadequate. To study the mechanism of neuronal necrosis, we previously established a Drosophila genetic model of neuronal necrosis by calcium overloading through expression of a constitutively opened cation channel mutant. Here, we performed further genetic screens and identified a suppressor of neuronal necrosis, CG17259, which encodes a seryl-tRNA synthetase. We found that loss-of-function (LOF) CG17259 activated eIF2α phosphorylation and subsequent up-regulation of chaperons (Hsp26 and Hsp27) and autophagy. Genetically, down-regulation of eIF2α phosphorylation, Hsp26/Hsp27 or autophagy reduced the protective effect of LOF CG17259, indicating they function downstream of CG17259. The protective effect of these protein degradation pathways indicated activation of a toxic protein during neuronal necrosis. Our data indicated that p53 was likely one such protein, because p53 was accumulated in the necrotic neurons and down-regulation of p53 rescued necrosis. In the SH-SY5Y human cells, tunicamycin (TM), a PERK activator, promoted transcription of hsp27; and necrosis induced by glutamate could be rescued by TM, associated with reduced p53 accumulation. In an ischemic stroke model in rats, p53 protein was also increased, and TM treatment could reduce the p53 accumulation and brain damage.

The pharmacokinetics of Lamotrigine (LTG) varies widely among patients with epilepsy. In this study, we are aiming to investigate the effects of OCT1, ABCG2, ABCC2 and HNF4α genetic polymorphisms on plasma LTG concentrations and therapeutic efficacy in Chinese patients with epilepsy.The study cohort comprised 112 Han Chinese patients with epilepsy who were receiving LTG monotherapy. Blood samples were taken and LTG levels were measured. The polymorphisms of OCT1 rs2282143, rs628031, ABCG2 rs2231142, rs2231137, ABCC2 rs2273697 and HNF4α rs2071197, rs3212183 were determined. The therapeutic efficacy of LTG at the 1-year time-point was assessed. Data analysis was performed using IBM SPSS Statistics 22.0.There were significant associations between OCT1 rs628031, ABCG2 rs2231142 polymorphisms and normalized LTG concentrations in patients with epilepsy (P0.05). On the other hand, polymorphisms of OCT1 rs2282143, ABCG2 rs2231137, ABCC2 rs2273697 and HNF4α rs2071197, rs3212183 exhibited no correlation with LTG concentrations. Additionally, no significant association existed between all the studied genotypes and LTG treatment response.These results suggested that the polymorphisms of OCT1 rs628031 and ABCG2 rs2231142 may affect LTG metabolism in Chinese patients with epilepsy. However, future studies are necessary to be investigated in a larger cohort of epileptic patients.

Background Age-related Macular Degeneration (AMD) is the leading cause of blindness. This study aims to analyze regional differences on the global burden of AMD and help direct related policy making. Methods Disability-adjusted life years (DALY) data were collected from the Global Burden of Disease Study (GBD) 2017 to estimate the AMD burden. Mean education years, human development index (HDI) and Public Health Expenditure were extracted from the Human Development Report 2018, and latitude data were obtained from the Google Earth. These four factors were analyzed to see their importance in regional differences of AMD burden, using Kruskal-Wallis test, Dunn’s multiple comparisons test as well as regression analysis. Results Global age-standardized DALY rates have decreased since 2011. Based on the WHO region system, age-standardized DALY rates in African and Eastern Mediterranean region were significantly lower than those of other four regions. Linear regression analysis indicated that age-standardized DALY rates were inversely related to HDI and mean education years. Conclusions The age-standardized AMD burden had a decreasing tendency recently. Lower socioeconomic status and fewer education years were associated with higher AMD burden. The finding of this study may highlight the importance of national development and education on relieving AMD burden.

This study investigated the lifetime prevalence of suicide attempts (SA) and independent demographic and clinical correlates in stabilized schizophrenia inpatients. A cross-sectional study was conducted in three psychiatric hospitals in Anhui province, an agricultural province located in east China. Psychopathology and depressive symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and Hamilton Depression Rating Scale (HAMD), respectively. A total of 315 stable schizophrenia inpatients were interviewed prior to discharge. The lifetime prevalence of SA was 22.2%. Multiple logistic regression analysis revealed that female gender (P

Role of surgery in the management of de novo stage IV breast cancer (BC) remains controversial. We aimed to determine the survival benefit of primary surgery on the basis of metastatic pattern.A retrospective cohort study based on the SEER database was conducted to identify patients with de novo stage IV BC diagnosed between 2010 and 2015. Patients were divided into surgery and non-surgery group, and propensity score weighting was used to balance clinicopathologic factors between groups.Of 8142 de novo stage IV BC patients, 1891 (23%) cases were managed with surgery and 6251 (77%) cases were managed without surgery. There were 3821 all-cause deaths and 3291 BC specific deaths over a median follow-up of 22 months. The weighted 3-year overall survival (OS) for the surgery group was 54.5%, compared to 47.7% (P 0.001) for the non-surgery group. The magnitude of the survival difference with surgery was significantly correlated with metastatic patterns (PThe survival benefit offered by surgery for de novo stage IV BC varies by metastatic patterns. Decisions for primary surgery of de novo stage IV BC patients should be tailored according to metastatic pattern.

The aim of the study was to compare the oncological and functional outcomes in localized prostate cancer patients who received non-whole-gland high-intensity focused ultrasound (HIFU) with those in patients who received whole-gland HIFU therapy.Eighty-six patients from September 2012 to January 2017 in our center were retrospectively analyzed. Oncological outcomes included histological absence of prostate cancer, biochemical disease-free survival (BDFS) as well as the absence of lesions suspected for harboring prostate cancer in multiparametric magnetic resonance imaging (mpMRI). Regarding functional outcomes, we determined international prostate symptom score (IPSS), pad-free rate, pad-free and leakage-free rates as well as international index of erectile function-5 (IIEF-5).Of the 86 patients, 25 patients who underwent non-whole-gland HIFU and 61 patients who underwent whole-gland HIFU were enrolled in our 1-year follow-up study. There were no significant differences in histological absence of prostate cancer (p = 0.655), BDFS (p = 0.820), prostate-specific antigen (PSA) nadir (p = 0.453), and absence of suspicious lesions in mpMRI (p = 0.633) between non-whole-gland HIFU group and whole-gland HIFU group. However, compared with the whole-gland HIFU, the non-whole-gland HIFU group had fewer IPSS at 1 month (8.64 ± 3.63 vs 10.85 ± 6.10), a longer time to PSA nadir (5.04 ± 2.07 vs 3.83 ± 1.65), less temporary urine retention rate (20.0% vs 44.3%), less complication rate especially urinary tract strictures (4% vs 26.2%), whereas pad-free rate, pad-free and leakage-free rates, and IIEF scores were comparable.Non-whole-gland HIFU is a promising type of treatment for localized prostate cancer with satisfactory oncological results with less impairment of functional outcomes and complications compared with whole-gland HIFU, but it requires longer follow-up and larger samples of randomized control trials.

Objective Oxidative stress is an important mechanism in the development of chronic complications in diabetes mellitus, and endothelial injury plays a key role in the pathogenesis of diabetic vascular injury. The present study was to investigate the role of inducible nitric oxide synthase (iNOS) induced peroxynitrite (ONOO-) in the aortic endothelial injury of diabetic rats.Methods/Results: Using RT-PCR, the mRNA of iNOS and nitrotyrosine (NT), a specific marker of ONOO-, were showed a significantly increased in the aortic endothelial diabetic rats, which was induced by streptozocin (STZ) and its increased protein content and distribution level were identified by Western blot and immunohistochemistry, respectively. Light microscope (hematocylin-eosin staining) and electron microscope (scanning and transmission) were employed to observe the morphological damage including nuclear shedding, mitochondria injury and inflammatory cell infiltration. We also measured the biochemical indicators of the diabetic rats, and the content of malondialdehyde (MDA), nitric oxide (NO), iNOS, endothelin (ET), and thromboxane B2 (TXB2) were increased and superoxide dismutase (SOD) was decreased. Conclusion: This study clarified that iNOS and its resultant exaggerated ONOO- formation, and this may play a key role in aortic endothelial injury of the diabetic rats. Thus, anti-iNOS maybe a potential therapy to prevent the ONOO- mediated oxidative stress injury.

Type 1 diabetes (T1D), an autoimmune disease, can be protected against by natural killer T (NKT) cells. Several attempts demonstrate that NKT cells also can be produced by inducing with Staphylococcus enterotoxin B (SEB) in addition to its classical activated antigen α-galactosylceramide. Here, we examined a potential usage of SEB-induced T (SEB-T) cells for the treatment of T1D. We established the immunophenotypes of SEB-T cells via flow cytometry, and in consequence, enriched in CD8(+)NKT cells after SEB stimulated. A high level of transforming growth factor β (TGF-β), detected by RT-PCR and ELISA, was first observed to be expressed and secreted by these SEB-T cells. Mixed lymphocyte reactions indicated that SEB-T cells could not produce a response to mitogens and allogeneic lymphocyte, and can inhibit lymphocytes response to mitogens. In an animal model, our data indicated that infusion of SEB-T cells in non-obese diabetic mice was well tolerated and could ameliorate hyperglycemia and maintain the blood glucose nearly on normal level until sacrifice. Strikingly, infusion of SEB-T cells resulted in an increase in the serum TGF-β level. These data raise the possibility that SEB-T cells can protect against T1D, which is associated with NKT cells generated in these SEB-induced cells.

Background Objections have been raised to performing risk-reducing salpingo-oophorectomy (RRSO) to reduce disease incidence and mortality of women with BRCA mutations. We aimed to examine the relationship between RRSO and breast cancer (BC) risk and mortality with a meta-analysis. Materials and Methods We conducted a comprehensive literature search using the PubMed and Embase databases for literature published from these databases' creation to September 2017. Hazard ratio (HR) estimates were identified directly from the original articles. Pooled results were calculated on the basis of nonoverlapping studies by fixed-effect meta-analysis. Results RRSO was associated with a significant reduction in the incidence of BC in women with BRCA1/2 mutations who had no history of BC (HR = 0.58; 95% confidence interval [CI], 0.37 to 0.78). Even in women with a history of BC, RRSO could reduce the risk of recurrence (HR = 0.50; 95% CI, 0.31 to 0.69). We further found that publication year was a critical interaction factor from a corresponding subgroup analyses in BC risk (Pheterogeneity = .024). In addition, we found that RRSO could improve the survival of women with BC (HR = 0.33; 95% CI, 0.28 to 0.38). Conclusion Summary estimates presented here indicate that RRSO was closely related to the reduced risk of BC caused by BRCA mutations, but publication year was a critical interaction factor and it should be noted that more recent studies have failed to find a significant reduction in BC risk associated with RRSO.

The gap junction protein alpha 8 (GJA8) gene has been widely studied in human congenital cataracts. However, little is known about its relationship with age-related cataract (ARC). In this study, three GJA8-tagged single nucleotide polymorphisms related to an increased ARC risk were identified: rs2132397 for general ARC under both dominant and additive models; rs7541950 for general ARC under both recessive and additive models; and rs6657114 for cortical cataract under the recessive model. To uncover the underlying mechanisms, this study also sought to explore whether GJA8 is involved in the autophagy process in human lens epithelial cells. The results showed that GJA8 may participate in autophagy to maintain the intracellular environment, which may be a novel mechanism for cataract formation induced by GJA8. In conclusion, this study identified the genetic susceptibility of GJA8 polymorphisms on ARC and provides new clues for fully understanding the pathological mechanism of GJA8 variants in affecting lens opacity. Electronic supplementary material The online version of this article (10.1007/s00439-018-1945-5) contains supplementary material, which is available to authorized users.

Converging evidence has shown the link between benign epilepsy with centrotemporal spikes (BECTS) and abnormal functional connectivity among distant brain regions. However, prior research in BECTS has not examined the dynamic changes in functional connectivity as networks form. We combined functional connectivity density (FCD) mapping and sliding windows correlation analyses, to fully capture the functional dynamics in patients with respect to the presence of interictal epileptic discharges (IEDs). Resting-state fMRI was performed in 43 BECTS patients and 28 healthy controls (HC). Patients were further classified into two subgroups, namely, IED (n = 20) and non-IED (n = 23) depending on the simultaneous EEG–fMRI recordings. The global dynamic FCD (dFCD) was measured using sliding window correlation. Then we quantified dFCD variability using their standard deviation. Compared with HC, patients with and without IEDs both showed invariable dFCD (decreased) among the orbital fontal cortex, anterior cingulate cortex and striatum, as well as variable dFCD (increased) in the posterior default mode network (P

Familial cortical myoclonic tremor with epilepsy is an autosomal dominant neurodegenerative disease, characterized by cortical tremor and epileptic seizures. Although four subtypes (types 1-4) mapped on different chromosomes (8q24, 2p11.1-q12.2, 5p15.31-p15.1 and 3q26.32-3q28) have been reported, the causative gene has not yet been identified. Here, we report the genetic study in a cohort of 20 Chinese pedigrees with familial cortical myoclonic tremor with epilepsy. Linkage and haplotype analysis in 11 pedigrees revealed maximum two-point logarithm of the odds (LOD) scores from 1.64 to 3.77 (LOD scores in five pedigrees were >3.0) in chromosomal region 8q24 and narrowed the candidate region to an interval of 4.9 Mb. Using whole-genome sequencing, long-range polymerase chain reaction and repeat-primed polymerase chain reaction, we identified an intronic pentanucleotide (TTTCA)n insertion in the SAMD12 gene as the cause, which co-segregated with the disease among the 11 pedigrees mapped on 8q24 and additional seven unmapped pedigrees. Only two pedigrees did not contain the (TTTCA)n insertion. Repeat-primed polymerase chain reaction revealed that the sizes of (TTTCA)n insertion in all affected members were larger than 105 repeats. The same pentanucleotide insertion (ATTTCATTTC)58 has been reported to form RNA foci resulting in neurotoxicity in spinocerebellar ataxia type 37, which suggests the similar pathogenic process in familial cortical myoclonic tremor with epilepsy type 1.

Our brain is a complex organ with different levels of interaction and therefore can be thought as a complex network. In high level interactions, the brain network is formed by interconnected areas called nodes and their connections are the links. Hubs play a key role in information processing in the brain. Brain networks can be extracted using several imaging modalities, here we focus on networks based on resting state fMRI (rsfMRI) where spontaneous brain activity is indirectly measured resulting in a blood-oxygen-level dependent (BOLD) signal for each voxel. Brain regions or voxels are said to be functionally connected and therefore, a link exists, if they present temporal correlation. The advantages of rsfMRI are the easiness of the acquisition suitable for children and clinical population and to be able to uncover networks related to spontaneous or “default mode” of the brain. Moreover, it has been shown that the resting state networks are impaired in psychiatric and neurological disorders.

The aim of this study was to investigate the association of depression and anxiety with adherence to antiepileptic drugs (AEDs) in Chinese patients with epilepsy.A total of 184 Chinese patients with epilepsy, and without cognitive impairment, underwent psychometric tests: the Beck Depression Inventory (BDI) and the Beck Anxiety Inventory (BAI). Adherence to antiepileptic drugs was measured by the eight-item Morisky Medication Adherence Scale (MMAS-8). Data on patients' demographic characteristics, disease characteristics, and treatment characteristics were also collected.The MMAS-8 indicated that 39.7% of the patients had low adherence, 34.2% had moderate adherence, and 26.1% had high adherence. Demographic, disease, and treatment characteristics were not significantly different between the low adherence group and the moderate-to-high adherence group. Thirty-six (19.6%) patients had moderate-to-severe depression according to the BDI, and 47 (25.5%) patients were considered anxious according to the BAI. A significant difference in depression scores was found between the low adherence group and the moderate-to-high adherence group (χ(2)=13.625, P0.001). We also found a significant difference in anxiety scores between the two groups (χ(2)=8.331, P=0.004). Pearson's correlations indicated that depression scores (r=-0.281, P0.001) and anxiety scores (r=-0.255, P0.001) were negatively correlated with adherence. Negative correlations were found between BDI scores and items 2, 7, and 8 of the MMAS-8 (P0.05); negative correlations were also found between BAI scores and items 3 and 6-8 (P0.05).Depression and anxiety were associated with reduced antiepileptic drug adherence in Chinese patients. Addressing depression and anxiety among patients with epilepsy may help improve adherence to AEDs.

Benign epilepsy with centrotemporal spikes (BECTS) is often associated with neural circuit dysfunction, particularly during the transient active state characterized by interictal epileptiform discharges (IEDs). Little is known, however, about the functional neural circuit abnormalities in BECTS without IEDs, or if such abnormalities could be used to differentiate BECTS patients without IEDs from healthy controls (HCs) for early diagnosis. To this end, we conducted resting-state functional magnetic resonance imaging (RS-fMRI) and simultaneous Electroencephalogram (EEG) in children with BECTS (n = 43) and age-matched HC (n = 28). The simultaneous EEG recordings distinguished BECTS with IEDs (n = 20) from without IEDs (n = 23). Intrinsic brain activity was measured in all three groups using the amplitude of low frequency fluctuation at rest. Compared to HC, BECTS patients with IEDs exhibited an intrinsic activity abnormality in the thalamus, suggesting that thalamic dysfunction could contribute to IED emergence while patients without IEDs exhibited intrinsic activity abnormalities in middle frontal gyrus and superior parietal gyrus. Using multivariate pattern classification analysis, we were able to differentiate BECTS without IEDs from HCs with 88.23% accuracy. BECTS without epileptic transients can be distinguished from HC and BECTS with IEDs by unique regional abnormalities in resting brain activity. Both transient abnormalities as reflected by IEDs and chronic abnormalities as reflected by RS-fMRI may contribute to BECTS development and expression. Intrinsic brain activity and multivariate pattern classification techniques are promising tools to diagnose and differentiate BECTS syndromes. Hum Brain Mapp 36:3878-3889, 2015. © 2015 Wiley Periodicals, Inc.

Objective The aim of this study was to evaluate the clinical reliability and validity of the Chinese version of the Neurological Disorders Depression Inventory for Epilepsy (C-NDDI-E). Methods A total of 248 Chinese patients with epilepsy underwent psychometric tests, including the Chinese version of the Mini International Neuropsychiatric Interview (C-MINI), the Chinese version of the Beck Depression Inventory — II (C-BDI-II), and the C-NDDI-E. Results None of the patients had difficulties understanding or completing the C-NDDI-E. Cronbach's α coefficient was 0.824. At a cutoff score of ≥ 14, the C-NDDI-E had a sensitivity of 0.854, a specificity of 0.899, a positive predictive value of 0.625, and a negative predictive value of 0.969. The scores for the C-NDDI-E were positively correlated with those for the C-BDI-II (P Conclusion The C-NDDI-E is a reliable and valid screening tool for the detection of major depression in Chinese patients with epilepsy.

To evaluate the efficacy and safety of self-retaining barbed suture (SRBS) application during laparoscopic partial nephrectomy (LPN), by assessing perioperative outcomes.Data from consecutive patients who underwent retroperitoneal LPN from January 2008 to December 2013 were retrospectively collected. Patients were divided into two groups according to suture techniques for renorrhaphy: the sliding clip technique and SRBS. The SRBS cases (Group 2 [G2]) were 1:1 matched with cases in the sliding clip group (Group 1 [G1]) for the PADUA score. Patient characteristics, perioperative outcomes, and renal function changes were compared between the groups.In total, 41 patients in G1 and 41 patients in G2 successfully underwent LPN. Patient characteristics, operative time, and complication rate were similar for both groups. Mean warm ischemia time was significantly shorter for the SRBS group (G1 versus G2, 27.5 versus 20.7 minutes; P.05). The estimated blood loss was similar in both groups. An improved early affected renal function recovery was observed in the SRBS group (percentage of glomerular filtration rate reduction for G1 versus G2, 29% versus 20.8%; P.05).The SRBS application offers an effective and safe renal parenchyma repair. In addition, SRBS appears to significantly minimize the warm ischemia injury and results in superior short-term renal function preservation.

OBJECTIVES Previous studies have reported that civilian transport is a mortality risk factor in low-resource communities. Few studies have analyzed the chief complaints associated with mortality involving civilian transport after an earthquake.Therefore, the present study was conducted to determine whether mortality resulting from medical professional transport differs from that involving civilian transport, and if so, the chief complaints associated with mortality involving civilian transport after the Wen-chuan earthquake. METHODS A hospital-based case-control study was conducted. Cases included all victims transported by civilians to West China Hospital from the disaster area (n=473). Controls included all victims transported by medical professionals to West China Hospital (n=1452). We further analyze six potential chief complaints of death to clarify the specific contributing chief complaints associated with mortality involving civilian transport. RESULTS Civilian transport is associated with significantly greater mortality compared with medical professional transport (Pearson's χ-test: P

Background Chemotherapeutic insensitivity and tumor cell invasiveness are major obstacles to effectively treating muscle-invasive bladder cancer (MIBC). Recent reports show that microRNAs (miRNAs) play an important role in the chemotherapeutic response and disease progression of MIBC. Therefore, here we investigated the role of miR-150 in MIBC cells in vitro. Material and methods miR-150 expression was quantified by qRT-PCR in two MIBC cell lines (5637 and T24). After successful miR-150 inhibition by transfection, MTS and transwell assays were used to assess the MIBC's cisplatin sensitivity and cell invasiveness, respectively. The TargetScan database and a luciferase reporter system were used to identify whether the programmed cell death 4 protein (PDCD4) is a direct target of miR-150 in MIBC cells. Results miR-150 expression was found to be significantly increased in both MIBC cell lines, and treatment with a miR-150 inhibitor significantly sensitized MIBC cells to cisplatin and inhibited MIBC cell invasiveness. PDCD4 was identified as a direct target of miR-150 in MIBC cells, and increased PDCD4 expression via transfection with the pLEX-PDCD4 plasmid efficiently sensitized MIBC cells to cisplatin chemotherapy and inhibited MIBC cell invasiveness. Conclusions This study provides novel evidence that miR-150 functions as a tumor promoter in reducing chemosensitivity and promoting invasiveness of MIBC cells via targeting PDCD4. Thus, modulation of the miR-150-PDCD4 axis shows promise as a therapeutic strategy for MIBC.