Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

OBJECTIVE To investigate the effect of leech freeze-dried powder combined with scorpion freeze-dried powder on carotid artery thrombosis in rats. METHODS FeCl3 was used to induce carotid artery thrombosis, and the experiment was divided into 6 groups: sham-operated group(sham group), model group, leech freeze-dried powder group(leech group), whole scorpion freeze-dried powder group(scorpion group), leech+scorpion half-dose group(half-dose group), leech+scorpion full-dose group(full-dose group), 6 rats in each group. The inhibition rate of bilateral carotid artery thrombosis was calculated after the final administration. The activated partial thromboplastin time(APTT), plasma prothrombintime(PT), plasma fibrinogen(FIB), and prothrombin time(TT) were measured by platelet aggregation and coagulation factor analyzer. The levels of plasma tissue-type plasminogen activator(t-PA) and plasminogen activatorinhibitor-I(PAI-I) were measured by ELSIA, and the thrombosis of each group was observed by HE staining. RESULTS Compared with model group, the wet weight and dry weight of thrombus were reduced in the leech, scorpion, half-dose and full-dose groups, and the full-dose group had the best effect in inhibiting thrombus formation. Compared with sham group, APTT, PT, TT was shortened, FIB content increased and t-PA level decreased in model group; compared with model group, APTT, PT, TT was prolonged, FIB content decreased and t-PA level increased in each dose group. The PAI-Ⅰ was not significantly different in each group. A large number of thrombus were seen in the blood vessels of model group. Compared with model group, there were significantly fewer thrombus in the leech, scorpion and half-dose groups, and almost no significant thrombus in the full-dose group. CONCLUSION Leech freeze-dried powder combined with scorpion freeze-dried powder inhibited carotid artery thrombosis in rats by affecting coagulation function and fibrinolytic system.

Schizophrenia (SCZ) is a highly destructive and complex psychiatric disorder illness, accompanied by a variety of positive and negative symptoms along with cognitive impairment, which brings a heavy social burden. Elucidation of the pathogenesis and therapeutic development is challenging because the complex interplay between genetic risk factors and environmental factors in essential neurodevelopmental processes. Therefore, preparing appropriate animal models can help people better understanding the neurobiological basis of SCZ and provide theoretical basis for finding new treatments. In order to provide reference for the application and improvement of SCZ animal models, this commentary reviewed several main modeling methods for animal models of SCZ, including neurodevelopmental models, drug-induced animal models, and genetic models, and the behavioral evaluation, histological analysis and possible molecular mechanisms of SCZ animal models were also outlined.

Autism spectrum disorder (ASD), a representative disease of children's neurodevelopmental disorders, brings huge pressure and financial burden to families and society. It is of great significance to explore its etiology and pathogenesis. Therefore, we established an ASD Cohort based on the existing China National Birth Cohort (CNBC), which applied parallel design to recruit and follow up families who achieved pregnancy after receiving assisted reproductive technologies (ART) and families with spontaneous conception. The main aims of this study are to compare the incidence of ASD among children born after ART with those born under spontaneous pregnancy, and to evaluate the impact of ART on the neurobehavioral development of offspring. Additionally, with a variety of clinical and behavioral related information collected during pregnancy and at early life of offspring, we are able to investigate the risk factors associated with ASD comprehensively. This article briefly introduces the objectives, contents, preliminary progress, strength and limitations, as well as further prospects of the ASD cohort study, mainly focusing on the overall design and current progress.

The importance of gut microbes to human health has gradually attracted attention. With the use of animal models, it has been revealed that maternal microbes during pregnancy could influence their children's health outcomes through shaping their microbial composition and regulating the development of their metabolic and immune system. However, the physiological mechanism of the human body is more complex and is affected by the interaction of multiple factors. The research results obtained from animal models are often inconsistent with human studies. At present, the influence of maternal intestinal microbes during pregnancy on the microbial colonization in their offspring and on a series of children's health outcomes is still unclear. Establishing a sub-cohort to detect the microbiome of the women across pregnancy and of their offspring, and further to integrate with variety of environmental and behavioral exposures can better provide reliable support for the research on the mechanism of children's health and diseases. This paper briefly introduces the research objectives, content, progress, strength and limitations of the sub-cohort study.

Objective:To understand the basic characteristics of COVID-19 cases and the virus carrying status of different samples in Ma′anshan.Methods:Descriptive epidemiological method was used to describe the distribution of 2019-nCoV infections in Ma′anshan. Real-time fluorescence RT-PCR was used to detect 2019-nCoV nucleic acid in sputum and/or throat swabs. Data was analyzed by EXCEL and SPSS 20.0. P<0.05 was considered to be statistically significant by using χ2 test. Results:Until 14 March 2020, 38 confirmed cases and no death had been reported in Ma′anshan, there were also 11 asymptomatic infections. 2019-nCoV infection was first detected on January 23, and the last was on February 20. No new infections have been found for 23 consecutive days until March 14; 77.55%(38/49)of the infections were in He county. Among the 1 447 subjects, the positive rate was 4.50% (27/600) in females and 2.60% (22/847) in males (χ 2=3.886, P=0.049). The minimum age of the infections was 4 years and the maximum was 85. There was no significant difference between age groups ( χ2=10.675, P=0.058). Among the 49 infections, 20 of them (40.82%) were from Wuhan, 24 (48.98%) were locally infected, and 5 (10.20%) were imported from other places. For the first positive infections, the positive rate of sputum (100%, 36/36) was higher than the throat swab (77.78%, 28/36), and the difference was statistically significant (χ 2=6.125, P<0.05). Conclusions:In Ma′anshan, 2019-nCoV infections were concentrated in He county, sputum was beneficial to the detection of 2019-nCoV.

Objective: To investigate the clinical efficacy of tight suturing for shortening healing scar tissues in repair of Myerson type III old rupture of Achilles tendon. Methods: A retrospective case series study was performed to analyze the clinical data of 16 patients with Myerson III type chronic Achilles tendon ruptures admitted to Sports Hospital Affiliated to Chengdu Sport University from January 2015 to December 2017. All of the patients were males with sports injuries, aged 19-71 years (mean, 40.6 years). The Achilles tendon defect was 5-7 centimeter (mean, 5.2 centimeter). The patients received tight suturing and shortening healing scar tissue for the repair. The operation time and surgical wound size were recorded. The clinical efficacy was evaluated by Amer-Lindholm standard and American 0rthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score. Meanwhile, the complications such as wound infection, Achilles tendon re-rupture, heel lifting weakness, muscle strength decline, ankle dysfunction, lameness and symptoms of sural nerve injury were recorded. Results: All patients were followed up for 11-41 months, with an average of 26 months. The operation time ranged from 25-51 minutes, with an average of 37 minutes. The incision was 4-12 cm, averaging 7 cm. According to the Amer-Lindholm standard, 14 patients were graded as excellent and two were graded as good, with the excellent and good rate of 100%. AOFAS ankle-hindfoot score increased from (42.7±6.8)points before operation to (95.1±4.9)points at the last follow-up (P<0.05). During the follow-up, there were no complications such as infection, Achilles tendon rupture, heel lifting weakness, muscle strength decline, ankle joint dysfunction, lameness and gastrocnemial nerve injury. Conclusion For Myerson type III old rupture of Achilles tendon, tight suturing for shortening healing scar tissue can increase the postoperative function scores without wound infection or complications.

Objective: To explorer factors related to spontaneous reduction in twin pregnancy following assisted reproductive technology. Methods: 2 848 twin pregnant women with treatment of vitro fertilization-embryo transfer (IVF-ET) or intra cytoplasmic sperm injection (ICSI) cycles were enrolled at Assisted Reproductive Centre of the First Affiliated Hospital of Nanjing Medical University, Nanjing Maternity Hospital and Shengjing Hospital of China Medical University from January 2013 to December 2016 respectively. Basic features of subjects, relevant clinical indicators, factors of assisted reproductive therapy and pregnancy outcome were collected from clinical assisted reproductive technology management system. According to the pregnancy outcome, the subjects with spontaneous reduction were classified as case group (n=686), and those with normal twin birth were classified as control group (n=2 162). The features of subjects in the two groups were compared. Non-conditional logistics regression model was used to analyze the related factors of the occurrence of spontaneous reduction. Results: The age of case group and control group were (30.6±4.3) and (30.2±4.0) years old respectively. After the adjustment of male sterile factor, compared to the subjects with luteinizing hormone level on the day of human chorionic gonadotropin administration (HCG) <1.43 IU/L, OR (95%CI) of the subjects with value at 2.59-5.10 IU/L was1.62 (1.08-2.42).Compared to the subjects with number of transferred embryo as 1, OR (95%CI) of the subjects with value as 3 was 0.23 (0.07-0.74). Compared to the subjects with stage of transferred embryo as cleavage stage, OR (95%CI) of the subjects with blastula stage was 0.42 (0.27-0.67). Conclusion Luteinizing hormone level on day of HCG, number and stage of embryo transfer are related factors to spontaneous reduction in twin pregnancy following assisted reproductive technology.

OBJECTIVE:To investigate the effects of different doses of tanshinone ⅡAon hemodynamics in patients underwent non-extracorporeal circulation coronary artery bypass grafting(NECCABG). METHODS:A total of 66 patients underwent selective NECCABG during Nov. 2016-Apr. 2017 were selected and divided into control group(33 cases)and observation group(33 cases) according to random number tablet. Both groups were given Tanshinone ⅡAsodium sulfonate injection with loading dose of 0.4 μg/kg for 10 min at the beginning of surgery. Control group was given Tanshinone ⅡAsodium sulfonate injection 0.2 μg/(kg·h) continuously till the end of surgery;observation group was given 0.4 μg/(kg·h)continuously till the end of surgery. HR,MAP, central venous pressure(CVP),mean pulmonary arterial pressure(MPAP),pulmonary capillary wedge pressure(PCWP),cardiac index(CI),systemic vascular resistance index(SVRI),pulmonary circulation resistance index(PVRI)and the occurrence of ADR were observed in 2 groups before anesthesia induction(T0),5 min after tracheal intubation(T1),at the moment of sternum cut(T2),at the end of anastomosis of anterior descending branch(T3),at the end of anastomosis of right coronary artery(T4),at the end of operation(T5). RESULTS:At T0,there was no statistical significance in HR,MAP,CVP,MPAP,PCWP, CI,SVRI or PVRI between 2 groups(P>0.05). At T1-T5, HR,MAP,CVP,MPAP,PCWP,SVRI and PVRI of control group were significantly higher than at T0,with statistical significance(P<0.05). There was no statistical significance in CI of control group among at T1-T5and with at T0;there was no statistical significance in HR,MAP,CVP,MPAP,PCWP,SVRI or PVRI of observation group between at T1-T5with at T0 (P>0.05). At T1-T5,CI of observation group was significantly higher than at T0and than control group;HR,MAP,CVP, MPAP,PCWP,SVRI and PVRI were significantly lower than control group,with statistical significance(P<0.05). No obvious ADR was found in 2 groups during medication. CONCLUSIONS:Tanshinone ⅡA0.4 μg/(kg·h)is helpful to keep hemodynamics stable and improve heart function in patients with NECCABG with good safety.

BACKGROUND AND PURPOSE: Large cohort studies on relationship between family history of stroke (FHS) and stroke risk are lacking in Asians. We aimed to systematically evaluate the association of FHS with stroke risk in a cohort study of 0.5 million Chinese adults. METHODS: Information about FHS was self-reported. The median follow-up time was 7.16 years and the end-point of follow-up was incident stroke, which was entered directly into the China Kadoorie Biobank system. Multivariate analyses were performed with Cox proportional hazards model, and interaction analyses were carried using likelihood-ratio tests. RESULTS: Compared with participants without FHS, the hazard ratio (HR) (95% confidence interval, CI) of stroke for participants with FHS was 1.50 (1.46-1.55). The HRs increased with the number of first degree relatives with stroke (HRs=1.41, 1.98 and 2.47 for 1, 2 and ≥3 relatives, respectively, P(trend) <0.001). The HRs were 1.57 (95% CI: 1.50-1.66) and 1.49 (95% CI: 1.45-1.54) for sibling history and parental history, respectively. Similar associations with offspring stroke risk were observed between paternal history (HR=1.48, 95% CI: 1.43-1.54) and maternal history (HR=1.49, 95% CI: 1.43-1.55). Moreover, significant interactions were detected between FHS and health-risk behaviors (tobacco smoking and alcohol drinking). CONCLUSIONS: FHS is an independent risk factor for stroke in Chinese. The more first degree relatives are affected by stroke, the higher are individuals’ risk of suffering from stroke. The management of the health-risk behaviors for reducing stroke should be highlighted, especially for the individuals with FHS.
Adult ; Asian Continental Ancestry Group ; China* ; Cohort Studies* ; Follow-Up Studies ; Humans ; Multivariate Analysis ; Parents ; Proportional Hazards Models ; Risk Factors ; Siblings ; Smoke ; Smoking ; Stroke*