This study was designed to investigate the effect of hypoxia on preeclampsia(PE)by modulating the Src/Siglec-6/SHP2 signaling pathway in the cytoplasm of trophoblast cells.Mouse model of PE was established in normal control and Siglec-6 knockdown mice by L-NAME administration,with aims of studying the changes in vascular diameter of spiral arteries in vivo and examining the expression levels of Siglec-6,p-Src,p-Shp2 and p-ERK1/2 proteins in mouse uterine vascular tissues.While,the effect of Src/Siglec-6/SHP2 on the invasive proliferation of trophoblast cells was explored by culturing human chorionic trophoblast cells HTR-8/SVneo with hypoxia in vitro.In vivo experimental assays showed that the diameter of spiral arteries was reduced in the Siglec-6 knockdown group of mice,and the expression levels of Siglec-6,p-Src,p-SHP2 and p-ERK1/2 proteins were significantly reduced.In vitro hypoxic HTR-8/SVneo cell model results revealed that Siglec-6 overexpression could promote trophoblast cell invasion and proliferation by regulating p-Src,p-SHP2,p-ERK1/2,MMP2,P53 and P21.While,suppression of Src and SHP2 eliminated Siglec-6 overexpression-mediated Siglec-6,p-Src,p-SHP2 and p-ERK1/2 expression,and inhibited the ability of Siglec-6 overexpression to mediate trophoblast invasion and proliferation.Taken together,Siglec-6 plays an important role in preeclampsia,and can alleviate preeclampsia by promoting trophoblast invasion and proliferation through the Src/SHP2 signalling pathway.

Objective To explore the protective effect and underlying mechanism of roxadustat(FG-4592),hypoxia-inducible factor-α(HIF-α)prolyl hydroxylase inhibitor,on brain injury caused by heat stroke(HS).Methods A total of 140 male C57BL/6J mice(6～8 weeks old,weighing 18～22 g)were subjected,and 40 of them were randomly divided into HS group,and low-,medium-and high-dose roxadustat groups(LD,MD and HD groups,5,10 and 20 mg/kg),with 10 mice in each group.The 24-hour survival rate was observed to determine the optimal dosage of roxadustat after modeling.Additionally,the remaining 100mice were randomly allocated to normal control(Control)group,roxadustat(FG-4592)group,HS group,and roxadustat+HS(FG-4592+HS)group,with 25 mice in each.Heat shock was inflicted to establish mouse model of HS.Modified neurological severity score(mNSS)was used to assess neurological function.HE staining of brain sections was performed to examine pathological damage,and Fluoro-Jade C staining was applied to observe neuronal degeneration.The activity of total superoxide dismutase(SOD)and content of malondialdehyde(MDA)in brain tissue were measured to assess oxidative stress.Transmission electron microscopy was employed to visualize mitochondrial damage.Western blotting was performed to assess the protein levels of Caspase-3,Cleaved Caspase-3,Mfn1,Mfn2,Opa1,Fis1,HIF-1α,HO-1 and p-Drp1(Ser616)/Drp1 ratio in the cerebral cortex.Results Compared to the HS group,FG-4592 significantly improved the survival rate of HS mice within 24 h,with the MD group showing the highest survival rate.Compared to the Control group,the HS group showed an increase in mNSS score(P＜0.05),an elevation in the MDA content in the cerebral cortex(P＜0.05),and a decrease in total SOD activity in the cerebral cortex(P＜0.05);HE staining revealed pathological damage in the cerebral cortex,and Fluoro-Jade C staining displayed obvious neuronal degeneration in the cerebral cortex;Electron microscopy revealed obvious mitochondrial structural damage in the cerebral cortex tissue;The protein expression of Caspase-3,Cleaved Caspase-3,Fis1,HIF-1α,HO-1 and p-Drp1(Ser616)/Drp1 ratio was increased(P＜0.05),while that of Mfn1,Mfn2,and Opa1 was decreased(P＜0.05).Pretreatment with FG-4592 significantly reduced the mNSS score in HS mice(P＜0.05),decreased MDA content(P＜0.05),and enhanced total SOD activity(P＜0.05).Additionally,FG-4592 pretreatment improved pathological damage in the cerebral cortex,reduced neuronal degeneration,and mitigated mitochondrial structural damage.Furthermore,it decreased the protein levels of Caspase-3,Cleaved Caspase-3,Fis1 and p-Drp1(Ser616)/Drp1 ratio(P＜0.05),while increased the levels of Mfn1,Mfn2,Opa1,HIF-1α,and HO-1(P＜0.05).Conclusion Roxadustat regulates the balance between mitochondrial fission and fusion,reduces mitochondrial structural damage,oxidative stress and apoptosis,and alleviates heat stroke-induced brain injury.

Background/Aims: Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China. Methods: A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators. Results: Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders. Conclusions In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

Objective:To assess the clinical effectiveness and safety of Omalizumab for treating pediatric allergic asthma in real world in China.Methods:The clinical data of children aged 6 to 11 years with allergic asthma who received Omalizumab treatment in 17 hospitals in China between July 6, 2018 and September 30, 2020 were retrospectively analyzed.Such information as the demographic characteristics, allergic history, family history, total immunoglobulin E (IgE) levels, specific IgE levels, skin prick test, exhaled nitric oxide (FeNO) levels, eosinophil (EOS) counts, and comorbidities at baseline were collected.Descriptive analysis of the Omalizumab treatment mode was made, and the difference in the first dose, injection frequency and course of treatment between the Omalizumab treatment mode and the mode recommended in the instruction was investigated.Global Evaluation of Treatment Effectiveness (GETE) analysis was made after Omalizumab treatment.The moderate-to-severe asthma exacerbation rate, inhaled corticosteroid (ICS) dose, lung functions were compared before and after Omalizumab treatment.Changes in the Childhood Asthma Control Test (C-ACT) and Pediatric Asthma Quality of Life Questionnaire (PAQLQ) results from baseline to 4, 8, 12, 16, 24, and 52 weeks after Omalizumab treatment were studied.The commodity improvement was assessed.The adverse event (AE) and serious adverse event (SAE) were analyzed for the evaluation of Omalizumab treatment safety.The difference in the annual rate of moderate-to-severe asthma exacerbation and ICS reduction was investigated by using t test.The significance level was set to 0.05.Other parameters were all subject to descriptive analysis.A total of 200 allergic asthma patients were enrolled, including 75.5% ( n=151) males and 24.5% ( n=49) females.The patients aged (8.20±1.81) years. Results:The median total IgE level of the 200 patients was 513.5 (24.4-11 600.0) IU/mL.Their median treatment time with Omalizumab was 112 (1-666) days.Their first dose of Omalizumab was 300 (150-600) mg.Of the 200 cases, 114 cases (57.0%) followed the first Omalizumab dosage recommended in the instruction.After 4-6 months of Omalizumab treatment, 88.5% of the patients enrolled ( n=117) responded to Omalizumab.After 4 weeks of treatment with Omalizumab, asthma was well-controlled, with an increased C-ACT score [from (22.70±3.70) points to (18.90±3.74) points at baseline]. Four-six months after Omalizumab administration, the annual rate of moderate-to-severe asthma exacerbation had a reduction of (2.00±5.68) per patient year( t=4.702 5, P<0.001), the median ICS daily dose was lowered [0 (0-240) μg vs. 160 (50-4 000) μg at baseline] ( P<0.001), the PAQLQ score was improved [(154.90±8.57) points vs. (122.80±27.15) points at baseline], and the forced expiratory volume in one second % predicted (FEV 1%pred) was increased [(92.80±10.50)% vs. (89.70±18.17)% at baseline]. In patients with available evaluations for comorbidities, including allergic rhinitis, atopic dermatitis or eczema, urticaria, allergic conjunctivitis and sinusitis, 92.8%-100.0% showed improved symptoms.A total of 124 AE were reported in 58 (29.0%) of the 200 patients, and the annual incidence was 0(0-15.1) per patient year.In 53 patients who suffered AE, 44 patients (83.0%) and 9 patients (17.0%) reported mild and moderate AE, respectively.No severe AE were observed in patients.The annual incidence of SAE was 0(0-1.9) per patient year.Most common drug-related AE were abdominal pain (2 patients, 1.0%) and fever (2 patients, 1.0%). No patient withdrew Omalizumab due to AE. Conclusions:Omalizumab shows good effectiveness and safety for the treatment of asthma in children.It can reduce the moderate-to-severe asthma exacerbation rate, reduce the ICS dose, improve asthma control levels, and improve lung functions and quality of life of patients.

OBJECTIVE To evaluate th e effects of comprehensive drug cost control in China ，and to provide reference for further improving the effects of cost control. METHODS Entropy method was used to establish a comprehensive evaluation index system of the comprehensive drug cost control effect from the respective of drug price control ability ，drug cost control ability and patient affordability. The comprehensively evaluate the effects of drug cost control in 31 provinces （autonomous regions and municipalities）during 2016-2020. The k-means cluster method was used to analyze the effects of comprehensive drug cost control in various provinces. RESULTS & CONCLUSIONS During the period of 2016-2020，the total score of comprehensive drug cost control effect of 31 provinces were 14.64，16.71，17.58，17.57，17.88，respectively. The results of cluster analysis were similar to the ranking of entropy method. Medical and health system reform policy had entered a stable period after achieving phased results ； the effects of comprehensive drug cost control was characterized by regional steps in 31 provinces；the effects of comprehensive drug cost control were better in developed coastal areas and some provinces and cities of western regions ，followed by provinces and cities in central China ；however，comprehensive drug cost control in 3 provinces of northeast China showed poor effect. The effects of comprehensive drug cost control in pilot cities of comprehensive medical reform were significantly improved. It is suggested that the successful experience of pilot cities of comprehensive medical reform should be promoted nationwide ，and policies such as volume-based drug procurement ，medical insurance drug price negotiation ，and diagnosis-related groups / diagnosis-intervention packet payment method reform should be further deepened.

Objective:To explore the relationship of sleep quality and sleep duration with hypertension among adults aged 30-79 years old in Guangzhou.Methods:According to multi-stage stratified cluster sampling, 12 747 residents aged 30-79 years old were sampled and surveyed in Guangzhou from January 2018 to March 2019. Data on general demographic characteristics, sleep quality, sleep duration and hypertension were collected through questionnaire survey, the Pittsburgh sleep quality index (PSQI) and physical examination. Multivariate logistic regression models were used to analyze the putative association between sleep quality, sleep duration and hypertension. Restrictive cubic spline curve was used to draw the dose-response relationship curve between sleep quality, sleep time and hypertension.Results:The mean age of the subjects was (52.68±12.17) years, the prevalence of hypertension was 36.6% (4 664/12 747), the average score of PSQI was (4.70±2.88), and the average sleep time was (7.00±1.32) hours. The prevalence of hypertension was positively associated with the PSQI score. Compared to the subjects with a score less than 3, OR (95% CI) of hypertension with a PSQI score of 3-5, 5-8, ≥9 were 1.14 (1.02-1.27), 1.17 (1.03-1.34), 1.41 (1.21-1.64), respectively. The relationship between sleep duration and hypertension appeared U-shaped. Compared with 6 to 8 hours sleep duration, both sleep duration<6 hours with OR(95% CI) of 1.27(1.12-1.43) or >8 hours with OR(95% CI) of 1.20(1.05-1.38) was associated with hypertension. Conclusion:Both poor sleep quality, longer or shorter sleep duration were responsible for increased risk of cognitive impairment in older Chinese.

Objective:To explore the relationship of sleep quality and sleep duration with hypertension among adults aged 30-79 years old in Guangzhou.Methods:According to multi-stage stratified cluster sampling, 12 747 residents aged 30-79 years old were sampled and surveyed in Guangzhou from January 2018 to March 2019. Data on general demographic characteristics, sleep quality, sleep duration and hypertension were collected through questionnaire survey, the Pittsburgh sleep quality index (PSQI) and physical examination. Multivariate logistic regression models were used to analyze the putative association between sleep quality, sleep duration and hypertension. Restrictive cubic spline curve was used to draw the dose-response relationship curve between sleep quality, sleep time and hypertension.Results:The mean age of the subjects was (52.68±12.17) years, the prevalence of hypertension was 36.6% (4 664/12 747), the average score of PSQI was (4.70±2.88), and the average sleep time was (7.00±1.32) hours. The prevalence of hypertension was positively associated with the PSQI score. Compared to the subjects with a score less than 3, OR (95% CI) of hypertension with a PSQI score of 3-5, 5-8, ≥9 were 1.14 (1.02-1.27), 1.17 (1.03-1.34), 1.41 (1.21-1.64), respectively. The relationship between sleep duration and hypertension appeared U-shaped. Compared with 6 to 8 hours sleep duration, both sleep duration<6 hours with OR(95% CI) of 1.27(1.12-1.43) or >8 hours with OR(95% CI) of 1.20(1.05-1.38) was associated with hypertension. Conclusion:Both poor sleep quality, longer or shorter sleep duration were responsible for increased risk of cognitive impairment in older Chinese.

Objective:To explore the effectiveness of evaluating voice disorders in dysarthria patients after brain injury using speech production measurements and analyze their phonics characteristics.Methods:Twenty-nine patients were divided into a severe dysarthria group ( n=19) and a mild dysarthria group ( n=10) through the subjective evaluation of their speech, and then evaluated using a computer speech monitor. The maximum phonation time (MPT), maximum counting ability (MCA), basic frequency (F0), standard deviation of F0 (F0SD), F0 range, intensity, formant, and the distance of jaw and tongue movements were recorded. Results:All of the patients displayed abnormal MPTs and MCAs, with the average MPT and MCA of the severe dysarthria group significantly lower than the mild group′s averages. In the severe dysarthria group, the abnormal F0s, F0SDs, F2(i)s and tongue movement distances were significantly greater than in the mild group.Conclusions:Speech production measurements can be applied to evaluate the speech dysarthria patients after brain injury. It is very common for such patients to have impaired speech and respiratory function, so this is worthy of attention.

Objective To explore the effect of action observation therapy on unilateral spatial neglect after stroke.Methods From March, 2017 to April, 2018, 44 patients with left-sided neglect due to unilateral right-sided vascular brain lesions were randomly divided into control group (n=22) and experimental group (n=22). The control group received the dynamic landscape video observation training, and the experimental group received the action observation training, based on routine rehabilitation, for three weeks. Before treatment, one week and three weeks after treatment, they were evaluated with Chinese Behavioral Inattention Test-Hong Kong version (CBIT-HK) routine tests (short line cancellation test, letter cancellation test, star cancellation test and line segment bisect), and the scores of Mini-Mental State Examination (MMSE), Fugl-Meyer Assessment (FMA) and Activities of Daily Living (ADL) were compared.Results One week after treatment, four scores of CBIT routine tests almost improved (t>2.712, P<0.05), and the score of line segment bisect was significantly better in the experiment group than in the control group (t=4.822, P<0.001). Three weeks after treatment, four scores of CBIT routine tests and the scores of MMSE, FMA and ADL improved in both groups (t>1.596, P<0.05), and the scores of short line cancellation test, letter cancellation test and line segment bisect were significantly lower in the experiment group than in the control group (t>3.577, P<0.01).Conclusion The action observation therapy could faciliate to improve the lateral neglect of patients after stroke.