Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a genetic cardiac muscle disease that accounts for approximately 30% sudden cardiac death in young adults. The Ser358Leu mutation of transmembrane protein 43 (TMEM43) was commonly identified in the patients of highly lethal and fully penetrant ARVD subtype, ARVD5. Here, we generated TMEM43 S358L mouse to explore the underlying mechanism. This mouse strain showed the classic pathologies of ARVD patients, including structural abnormalities and cardiac fibrofatty. TMEM43 S358L mutation led to hyper-activated nuclear factor κB (NF-κB) activation in heart tissues and primary cardiomyocyte cells. Importantly, this hyper activation of NF-κB directly drove the expression of pro-fibrotic gene, transforming growth factor beta (TGFβ1), and enhanced downstream signal, indicating that TMEM43 S358L mutation up-regulates NF-κB-TGFβ signal cascade during ARVD cardiac fibrosis. Our study partially reveals the regulatory mechanism of ARVD development.

Objective To evaluate the effect of surgery-radiotherapy interval (SRI) on clinical prognosis of locally advanced stage c Ⅱ-Ⅲ breast cancer patients treated with neoadjuvant chemtherapy and modified radical mastectomy.Methods Clinical data of 1 087 breast cancer patients treated with neoadjuvant chemotherapy and modified radical mastectomy from 11 hospitals in China were retrospectively analyzed.The optimal threshold value of SRI upon clinical prognosis was determined by maxstat method.The effect of SRI on clinical prognosis was evaluated by using multivariate Cox regression analysis and propensity score matching (PSM).Results The median follow-up time was 72.9 months.The 5-year disease-free survival (DFS) and overall survival (OS) rates were 68.1％ and 81.8％.All patients were divided into SRI ≤18 weeks (n=917) and SRI＞ 18 weeks groups (n=170).Multivariate Cox regression analysis demonstrated that hormone receptor status (P＜0.001),pathological T stage (P＜0.001),pathological N stage (P＜0.001) and SRI (P=0.023) were independent influencing factors of DFS.Hormone receptor status (P=0.013),pathological T stage (P=0.006),pathological N stage (P＜0.001),endocrine therapy (P=0.013) and SRI (P=0.001) were significantly associated with OS.After balancing the clinical and pathological factors with PSM,patients with SRI＜ 18 weeks had superior DFS and OS to those with SRI＞ 18 weeks.Conclusions SRI affects the clinical prognosis of locally advanced breast cancer patients treated with neoadjuvant chemotherapy and modified radical mastectomy.Radiotherapy should be performed within 18 weeks after mastectomy.

Objective To investigate the effects of rotavirus ( RV) on the expression and bioactiv-ity of Na+-H+ exchanger 3 ( NHE3 ) in Caco-2 cells and the possible regulatory mechanism. Methods Caco-2 cells expressing NHE3 were constructed and divided into four groups as follows: control ( CTL ) group, RV group, BAPTA-AM ( a Ca2+ chelator) group and BAPTA-AM+RV group. Na+-H+ exchanger ac-tivity and NHE3 expression on cell surface were determined using BCECF-AM and biotinylation assay, re-spectively. Expression of Cdc42 at protein level was measured by Western blot. Results Compared with the control group, RV infection significantly decreased the activity of NHE3 and its expression on cell surface. BATPA-AM antagonized the inhibitory effects on NHE3. Moreover, the expression of Cdc42 at protein level was increased following RV infection, which was also antagonized by BATPA-AM. Conclusions Intracellu-lar Ca2+-mediated Cdc42-dependent endocytosis pathway might be involved in regulating the expression and bioactivity of NHE3 during RV infection.

Objective To compare the efficacy of the solid tumor evaluation criteria 1.1 (RECIST 1.1) and the revised solid tumor efficacy evaluation criteria (mRECIST) after chemotherapy in the hepatocellular carcinoma system.Methord Retrospective analysis of 34 patients with advanced hepatocellular carcinoma who underwent Folfox4 system chemotherapy from the Department of Hepatobiliary and Pancreatic Surgery of Dongfeng Hospital affiliated to Hubei Medical College from July 2017 to July 2018,including 24 males and 10 females.Spiral CT and/or MRI (four-phase) scans were performed 1 nonth,2 months,and every 2 months after treatment,and the effects were evaluated by RECIST 1.1 and mRECIST,respectively.The survival curve was drawn by Kaplan-Meier method,and log-rank test was used to compare survival curves.Result In 34 patients evaluated with the RECIST 1.1 criteria,0 patient showed complete remission (CR),6 patients partial remission (PR),20 patients stable disease (SD),and 8 patients progressive disease (PD).Using the mRECIST criteria,CR:0,PR:10,SD:17,and PD:7 patients.The Kappa value of the two methods was 0.271,95％ CI:0.010 ～0.535.The log-rank test showed that there was no significant difference in the survival curves of patients between PR,SD and PD in RECIST 1.1 (P ＞ 0.05).The cumulative survival rates were 40.0％,11.8％ and 0,respectively.The survival curves of patients with PR,SD and PD in mRECIST were statistically significant (P ＜ 0.05),and the cumulative survival rates were 37.5％,0,and 0,respectively.Conclusion The mRECIST criteria were more suitable than the RECIST 1.1 criteria in assessing efficacy of systemic chemotherapy for hepatocellular carcinoma.

Variation of maternal gut microbiota may increase the risk of autism spectrum disorders (ASDs) in offspring. Animal studies have indicated that maternal gut microbiota is related to neurodevelopmental abnormalities in mouse offspring, while it is unclear whether there is a correlation between gut microbiota of ASD children and their mothers. We examined the relationships between gut microbiome profiles of ASD children and those of their mothers, and evaluated the clinical discriminatory power of discovered bacterial biomarkers. Gut microbiome was profiled and evaluated by 16S ribosomal RNA gene sequencing in stool samples of 59 mother-child pairs of ASD children and 30 matched mother-child pairs of healthy children. Significant differences were observed in the gut microbiome composition between ASD and healthy children in our Chinese cohort. Several unique bacterial biomarkers, such as Alcaligenaceae and Acinetobacter, were identified. Mothers of ASD children had more Proteobacteria, Alphaproteobacteria, Moraxellaceae, and Acinetobacter than mothers of healthy children. There was a clear correlation between gut microbiome profiles of children and their mothers; however, children with ASD still had unique bacterial biomarkers, such as Alcaligenaceae, Enterobacteriaceae, and Clostridium. Candidate biomarkers discovered in this study had remarkable discriminatory power. The identified patterns of mother-child gut microbiome profiles may be important for assessing risks during the early stage and planning of personalized treatment and prevention of ASD via microbiota modulation.
Adult ; Animals ; Autism Spectrum Disorder ; microbiology ; Bacteria ; classification ; genetics ; isolation & purification ; Biomarkers ; Child ; Child, Preschool ; Cohort Studies ; Female ; Gastrointestinal Microbiome ; Humans ; Male ; Mice ; Mothers ; Risk Assessment

Objective To investigate the efficacy and safety of leukoreduction therapy in severe per-tussis in infants. Methods Therapeutic processes of 3 cases of severe pertussis in PICU of Shanghai Children′s Medical Center were retrospectively studied from October 2017 to May 2018. We reviewed the related literatures and summarized the time and effectiveness of leukoreduction therapy in severe pertussis. Results All 3 cases had leukocytosis,respiratory faliure,pulmonary hypertension and right heart failure. One case had multiple organ failure before undergoing exchange transfusion therapy and eventually died. Two cases that had pulmonary hypertension during the period of WBC′s rising accepted leukopheresis therapy before multiple organ failure,and eventually survived. We reviewed the foreign literatures which was almost case reports,leukoreduction therapy might improve the prognosis of severe pertussis in infants,but the time of using it had no conclusion. Conclusion This is the first report of leukoreduction therapy for the severe per-tussis in infants in China. It provides a new method for the treatment of severe pertussis in infants. It is worth looking forward to use this method combined with continuous renal replacement therapy and extracorporeal membrane oxygenation technology. In the future,multicenter clinical research should be done to explore the effectiveness and safety of leukoreduction therapy in the severe pertussis in infants.

Objective To investigate the efficacy of leflunomide combined with prednisone in the induction therapy of proliferative lupus nephritis (LN).Methods A prospective,multicenter,randomized controlled clinical trial was conducted in patients with biopsy-proved proliferative lupus nephritis recruited from 15 renal centers from 2013 to 2015.Patients were randomized to two groups.Oral leflunomide or intravenous cyclophosphamide was given to patients in each group.Both groups received a tapering course of oral prednisone therapy.All patients were followed up for 24 weeks.The blood biochemistry,urine index,clinical curative effect and adverse reaction were recorded and analyzed statistically.Results A total of 100 patients were enrolled in this clinical trial,including 48 patients in leflunomide group and 52 patients in cyclophosphamide group.After 24 weeks,the overall response rate was 79％ (95％ CI 67％-90％) in the leflunomide group and 69％ (95％ CI 56％-82％) in the cyclophosphamide group.23％ (95％CI 11％-35％) of patients in leflunomide group showed complete remission compared with 27％ (95％CI 24％-30％) in cyclophosphamide group (P=0.35).The levels of 24-hr urine protein excretion,SLEDAI and anti-dsDNA antibody titers were decreased in patients treated with leflunomide group after 24-weeks treatment.And the levels of serum albumin and complement 3 after treatment were significantly higher compared with these before treatment.There was also no significant difference in changes of 24-hr urine protein excretion,SLEDAI score,anti-dsDNA antibody titers,serum albumin and complement C3 levels after treatment between two groups.Incidence of adverse events did not differ between the leflunomide and cyclophosphamide group.Conclusions Leflunomide combined with prednisone showed same efficacy compared with cyclophosphamide as induction therapy for lupus nephritis.Leflunomide might be an useful medicine in the induction therapy of lupus nephritis.

Objective To observe the effects and regulatory mechanism of rotavirus infection on the expression and bioactivity of Na+/H+exchanger 3 (NHE3) on Caco-2 cells. Methods A cell model of Caco-2 cells expressing NHE3 was constructed. Four groups were set up,which were control(CTL) group, rotavirus(RV) infection group, Cdc42 inhibitor (Pirl-1) group and Pirl-1+RV group. Bioactivity and ex-pression of NHE3 on the surface of Caco-2 cells were determined by BCECF-AM and biotinylation method, respectively. Expression of Cdc42 protein was measured by Western blot. Co-immunoprecipitation was per-formed to detect the interaction between NHE3 and Cdc42. Results Compared with the CTL group,RV in-fection significantly inhibited the bioactivity and expression of NHE3 on Caco-2 cells. These inhibitory effects were antagonized by Pirl-1. Moreover,RV infection enhanced the expression of Cdc42 protein and promoted the interaction between NHE3 and Cdc42, which were also antagonized by Pirl-1. Conclusion RV infec-tion might regulate the expression and bioactivity of NHE3 through Cdc42-dependent endocytosis pathway.

Objective To explore the value of microvascular angiography in evaluating the neovascularization of internal carotid artery plaque and the prediction of cerebral infarction.Methods A total of 100 patients with suspected cerebral infarction received from March 19th,2016 to December 1 st,2017 in our hospital were enrolled in this study.All patients underwent microvascular imaging and then analyzed the importance of this technique in evaluating cerebral infarction,plaque neovascularization.Results 100 lesions were recorded in 100 patients,among which there were 22 cases with no superb microvascular ultrasound imaging (SMI) and blood flow signal (ie,score 0) in the plaque.SMI imaging could better show neovascularization (ie score 1 or 2 points).In 78 cases,they all grew from the arterial wall to the plaque.There were 61 cases of cerebral infarction in the blood flow group (78.2％),8 cases (36.3％) of cerebral infarction in the group without blood flow,with statistical significance(P =0.023).SMI imaging was highly sensitive to the prediction of cerebral infarction incidence,reaching 88.4％.Conclusions Ultra-microvascular imaging can improve the sensitivity of cerebral infarction prediction and promptly detect neovascularization of internal carotid artery plaque,thus providing a basis for clinical treatment.

Objective To translate the English version of Safety Attitudes Questionnaire (SAQ) into Chinese,and to test the reliability and validity of the Chinese version of SAQ. Methods The SAQ was developed into Chinese version through translation, back-translation and cross-culture adaption. The reliability and validity of the Chinese version of SAQ were tested in 823 first-line nurse managers in Henan. Results The scale content validity index was 0.90 of the Chinese SAQ, and the item content validity index ranged from 0.83 to 0.96. The correlations between the items and the full scale, the dimensions and the full scale separately ranged from 0.32 to 0.64 and 0.50 to 0.81 (P<0.01). The confirmatory factor analysis resulted in a good model fit for the six dimensions and the full construct, the goodness-of-fit index was 0.96, Tucker-Lewis index was 0.93, comparative fit index was 0.95, and root mean square error of approximation was 0.06. The Cronbach alpha coefficient for the scale was 0.913 and for the six dimensions were 0.565, 0.655, 0.825, 0.804, 0.880, 0.725 separately, the test-retest reliability coefficient was 0.934. Conclusions The Chinese version of SAQ is a valid and reliable tool to assess the safety culture of first-line nurse managers in Chinese hospitals.