ObjectiveTo investigate the effects of Schisandrae Chinensis Fructus lignans on schizophrenia induced by dizocilpine maleate （MK-801） in mice and to clarify its mechanism. MethodsMale mice of 4-6 weeks old were randomized into blank， model， positive drug， and low-， medium-， and high-dose （40， 80， 160 mg·kg^-1， respectively） Schisandrae Chinensis Fructus lignans groups. The blank group was administrated with distilled water， and the other groups were injected with 0.5 mg·kg^-1 MK-801 to induce schizophrenia symptoms. Meanwhile， risperidone was injected at 0.2 mg·kg^-1 in the positive drug group， and mice in the intervention groups were injected with corresponding drugs for 14 consecutive days. The behavioral changes of mice were observed by autonomous activity test， open field test， forced swimming test， and water maze test. The levels of dopamine （DA） and 5-hydroxytryptamine （5-HT） in the brain and tumor necrosis factor-α （TNF-α） and nuclear factor-κB （NF-κB） in peripheral blood were quantified by enzyme-linked immunosorbent assay （ELISA）. The changes in the prefrontal lobe of mice were observed by hematoxylin-eosin staining， and the changes of the hippocampal tissue were observed by Nissl staining. The protein levels of silencing information regulatory factor 1 （SIRT1） and forkhead box protein O3a （FoxO3a） in the hippocampus of mice were determined by Western blot. ResultsCompared with the model group， low， medium， and high doses of Schisandrae Chinensis Fructus lignans reduced the total number of autonomous activities， total distance in the open field test， immobile time in the forced swimming test， and levels of TNF-α and NF-κB in peripheral blood （P<0.05）， while increasing the number of platform crossings in the water maze test and DA and 5-HT levels in the brain tissue （P<0.05）. Compared with the model group， risperidone and low， medium， and high doses of Schisandrae Chinensis Fructus lignans improve the neural cell morphology in the CA1 region， with full cells in neatly dense arrangement and exhibiting clear membrane boundary. Schisandrae Chinensis Fructus lignans inhibited the expression of SIRT 1 and FoxO3a in the hippocampus （P<0.05）. ConclusionTo sum up， Schisandrae Chinensis Fructus lignans may improve the behavior of schizophrenic mice by activating the SIRT1/FoxO3a signaling pathway to exert neuroprotective effects.

Background Air pollution exposure has a significant impact on maternal and child health. However, the research on the association between ambient ozone (O₃) exposure during pregnancy and the risk of premature birth in newborns is limited, and the conclusions are inconsistent. Objective To investigate the association of ambient O₃ exposure during pregnancy with the risk of preterm birth in Guangdong Province. Methods Data of pregnant women in Guangzhou from 2013 to 2019 and Foshan from 2018 to 2023 were collected, and O₃ concentrations during different trimesters were assessed according to maternal residential addresses. Bilinear interpolation was used to evaluate the concentrations of air pollution. A cohort study design was adopted in our study. Restricted cubic spline curves were used to evaluate the exposure-response relationship between O₃ exposure and preterm birth risk and explore potential exposure threshold of O₃. Logistic regression models were used to evaluate the association of O₃ exposure with preterm birth. Results A total of 702 924 pregnant women were included in this study, of whom 43 051 (6.12%) were preterm. The average O₃ exposure concentrations of pregnant women during the first, second, third, and whole trimesters were 95.51, 97.51, 100.60, and 97.87 μg·m⁻³, respectively. We observed J-shaped associations between O₃ exposure and preterm birth risk during the second, third, and whole trimesters of pregnancy using restricted cubic spline curves. This study found that there were threshold concentrations between O₃ exposure and preterm birth risk during different gestational periods, and the threshold concentrations in the first, second, third, and whole trimesters were 112.32, 99.83, 111.74, and 112.46 μg·m⁻³, respectively. During the second, third, and whole trimesters of pregnancy, after adjusting for maternal age, baby sex, pre-pregnancy body mass index, mode of delivery, baby birth weight, gestational diabetes, and gestational hypertension, the odds ratios (OR) of preterm birth were 1.02 (95%CI: 1.01, 1.04), 1.02 (95%CI: 1.00, 1.03), and 1.17 (95%CI: 1.13, 1.21) for each 10 μg·m⁻³ increase in O₃ concentration above the O₃ threshold. No significant association was found between O₃ exposure and the risk of preterm birth during the first trimester. Conclusion There is a nonlinear association between the risk of preterm birth and O₃ exposure during pregnancy, and higher concentrations of O₃ exposure during pregnancy are associated with the risk of preterm birth. Above the O₃ threshold concentration during pregnancy, especially during the second, third, and whole trimesters, the risk of preterm birth elevates with the increase of O₃ exposure concentrations.

Objective:To study the correlation between zinc finger protein A20 (A20) and basic fibroblast growth factor (BFGF) and liver fibrosis in chronic hepatitis B.Methods:A retrospective study was conducted to select 120 patients with chronic hepatitis B diagnosed and treated in the Fifth Hospital of Shijiazhuang City from January 2019 to December 2020, all of whom underwent liver tissue biopsy, and 25 cases of liver pathological specimens who underwent liver hemangioma resection were selected. The correlation between the expression of A20 and BFGF in liver tissue and the stage of hepatic fibrosis and inflammation were analyzed.Results:The expression of A20 in the S1 - S4 phase was higher than that in the S0 phase: (6.12 ± 1.22)%, (10.18 ± 2.43)%, (16.94 ± 5.06)%, (25.99 ± 7.57)% vs. (0.81 ± 0.29)%; the expression of BFGF in the S1 - S4 phase was higher than that in the S0 phase: (6.12 ± 1.22)%, (10.18 ± 2.43)%, (16.94 ± 5.06)%, (25.99 ± 7.57)% vs. (0.81 ± 0.29)%, there were statistical differences ( P<0.05). The expression of A20 in the G1 - G4 phase was higher than that in the G0 phase: (6.56 ± 1.87)%, (10.01 ± 3.29)%, (15.54 ± 5.01)%, (25.86 ± 8.02)% vs. (0.85 ± 0.71)%; the expression of BFGF in the G1 - G4 phase was higher than that in the G0 phase: (5.91 ± 1.52)%, (9.65 ± 2.48)%, (15.03 ± 4.86)%, (24.62 ± 7.22)% vs. (0.79 ± 0.41)%, there were statistical differences ( P<0.05). The results of Pearson test showed that there was a positive correlation between liver A20 and BFGF ( r = 0.824, P<0.05). Conclusions:The expressions of A20 and BFGF in liver tissue increase with the aggravation of liver pathological fibrosis and inflammation, which can be used as important indicators to evaluate the severity of liver fibrosis.

Objective To investigate the protective effect of dimethyl fumarate(DMF)on doxorubicin(DOX)-induced cardiac injury in mice and its possible mechanism.Methods Eighteen male C57BL/6J mice were selected and randomly divided into control group,model group and treatment group,with 6mice in each group.In the model group,DOX(2.5mg/kg)was injected intraperitoneally for two weeks,once every three days,with a total of 15mg/kg;the control group was given equal proportion of normal saline.The experi-mental group was also treated with DOX for two weeks,and was given DMF(25mg/kg)once a day for consecutive seven days after the first week.The cardiac function of mice was monitored at0,3,7 and 14 days.The atrial natriuretic peptide(ANP)and brain natriuretic peptide(BNP)mRNA expression of myocardial were detected by real-time quantitative polymerase chain reaction(RT-qPCR),and plasma creatine kinase isoenzyme(CK-MB)and lactic acid dehydrogenase(LDH)levels were measured by ELISA(enzyme-linked immunosorbent assay).Hematoxylin-eosin(HE)staining was used to observe myocardial structure.Malondialdehyde(MDA),reduced glutathione(GSH),and oxidized glutathione(GSSG)content and superoxide dismutase(SOD)activity were measured;Western blot was used to detect the expression of nuclear factor erythroid-2-related factor 2(Nrf2),heme oxygenase-1(HO-1)and glutathione peroxidase 4(GPX4),a key protein of ferroptosis.Results In the model group,the heart function of mice continued to decline and reached the lowest level at 14days,left ventricular ejection fraction(LVEF)and left ventricular short-axis shortening rate(LVFS)were significantly lower than those in control group.Body weight and heart weight-to-tibia length ratio were lower than those of control group,while the mRNA expression of cardiac ANP and BNP was increased,the plasma CK-MB and LDH were increased,accompanied by cardiomyocyte edema,muscle fiber rupture and inflammatory infiltration.However,the cardiac dysfunction of mice in the treatment group was improved,and the myocardial damage and structural destruction were less severe.In addition,MDA and GSSG contents in the model group were significantly higher than those in the control group,GSH level and SOD activity were lower than those in the control group,and the expressions of Nrf2,HO-1 and GPx4 were decreased.Compared with the model group,the cardiac oxidative stress in the treatment group was improved,and the expressions of Nrf2,HO-1 and GPx4 were also up-regulated.Conclusion DMF inhibits fer-roptosis and alleviates DOX-induced cardiac oxidative stress through upregulation of Nrf2/HO-1/GPX4 pathway,thus improving cardi-ac damage.

Currently, there are limited strategies for convenient and rapid wound repair in clinical practice. In recent years, in-situ cell electrospinning (IS-CE) technology, developed from in-situ electrospinning (IS-E) technology, has emerged. IS-CE technology involves encapsulating living cells within micro-nanofibers to construct living fibrous tissue scaffolds in situ, making some progress in wound repair applications. However, this technology still faces limitations such as low cell survival rate and poor fiber stability. This article provides a comprehensive review on the current status of both IS-E and IS-CE technologies, as well as the application of IS-CE technology in wound repair. In addition, the advantages, limitations, and improvement methods of IS-CE technology applied in wound treatment are emphatically discussed, aiming to provide insights for its application in tissue engineering and wound repair.

Objective:We aimed to analyse the trend of incidence and mortality of stomach cancer in Shandong province from 2012 to 2022 and predict the development trend from 2023 to 2030.Methods:Data on incidence and mortality of stomach cancer in Shandong province from 2012 to 2022 were obtained from Shandong Cancer Registry. The incidence, age-specific incidence, mortality and age-specific mortality in different years, sexes and urban and rural areas were calculated, the rates were standardized based on the age composition of the Chinese standard population in 2000. The average annual percent change (AAPC) of incidence and mortality was calculated using Joinpoint software. The Bayesian age-period-cohort model was used to predict the trend of stomach cancer incidence and mortality from 2023 to 2030.Results:From 2012 to 2022, the stomach cancer age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) showed a decreasing trend. The ASIR decreased from 27.47/100 000 in 2012 to 16.06/100 000 in 2022 (AAPC=-5.10%, P＜0.001), and the ASMR decreased from 17.69/100 000 to 11.09/100 000 (AAPC=-5.52%, P＜0.001). The ASIR and ASMR of male, female, urban and rural population also showed downward trends. The incidence and mortality rates of men were always higher than those of women, and the difference between urban and rural areas is gradually narrowing. In 2022, the ASIR (16.09/100 000 in urban and 16.03/100 000 in rural) and the ASMR (11.10/100 000 in urban and 11.08/100 000 in rural) of stomach cancer between urban and rural areas were nearly identical. The Bayesian age-period-cohort model predicted that the ASIR of stomach cancer in Shandong would further decrease from 2023 to 2030 (AAPC=-0.51%, P=0.001), but the change tended to be smooth. The incidences in male (AAPC=-1.46%, P=0.010) and rural areas (AAPC=-1.21%, P＜0.001) were still expected to have a little room for decline. The trend of incidences in female and urban areas were not statistically significant. The trend of mortality was consistent with the incidence. Conclusions:The stomach cancer incidence and mortality in Shandong shows a decreasing trend and it is expected to decrease further by 2030. However, the trend tends to be smooth, and the disease burden should be reduced as early as possible for high-risk population and high-risk factors of stomach cancer.

Objective To improve the efficiency of induced differentiation of primitive neural epithelial cells derived from human induced pluripotent stem cells(hiPSCs-NECs)into functional midbrain dopaminergic progenitor cells(DAPs).Methods HiPSCs were cultured in mTeSRTM medium containing DMH1(10 μmol/L),SB431542(10 μmol/L),SHH(200 ng/mL),FGF8(100 ng/mL),purmorphamine(2 μmol/L),CHIR99021(3 μmol/L),and N2(1%)for 12 days to induce their differentiation into primitive neuroepithelial cells(NECs).The hiPSCs-NECs were digested with collagenase IV and then cultured in neurobasal medium supplemented with 1%N2,2%B27-A,BDNF(10 ng/mL),GDNF(10 ng/mL),AA,TGF-β,cAMP,and 1%GlutaMax in the presence of different concentrations of Rho kinase inhibitor Y27632,and the culture medium was changed the next day to remove Y27632.Continuous induction was performed until day 28 to obtain DAPs.Results Human iPSCs expressed the pluripotency markers OCT4,SOX2,Nanog,and SSEA1 and were positive for alkaline phosphatase staining.The hiPSCs-NECs were obtained on day 13 in the form of neural rosettes expressing neuroepithelial markers SOX2,nestin,and PAX6.In digested hiPSCs-NECs,the addition of 5 μmol/L Y27632 significantly promoted survival of the adherent cells,increased cell viability and the proportion of S-phase cells(P<0.01),and reduced the rate of apoptotic cells(P<0.05).On day 28 of induction,the obtained cells highly expressed the specific markers of DAPS(TH,FOXA2,NURR1,and Tuj1).Conclusion Treatment with Y27632(5 μmol/L)for 24 h significantly promotes the survival of human iPSCs-NECs during their differentiation into DPAs without affecting the cell differentiation,which indirectly enhances the efficiency of cell differentiation.

Objective To improve the efficiency of induced differentiation of primitive neural epithelial cells derived from human induced pluripotent stem cells(hiPSCs-NECs)into functional midbrain dopaminergic progenitor cells(DAPs).Methods HiPSCs were cultured in mTeSRTM medium containing DMH1(10 μmol/L),SB431542(10 μmol/L),SHH(200 ng/mL),FGF8(100 ng/mL),purmorphamine(2 μmol/L),CHIR99021(3 μmol/L),and N2(1%)for 12 days to induce their differentiation into primitive neuroepithelial cells(NECs).The hiPSCs-NECs were digested with collagenase IV and then cultured in neurobasal medium supplemented with 1%N2,2%B27-A,BDNF(10 ng/mL),GDNF(10 ng/mL),AA,TGF-β,cAMP,and 1%GlutaMax in the presence of different concentrations of Rho kinase inhibitor Y27632,and the culture medium was changed the next day to remove Y27632.Continuous induction was performed until day 28 to obtain DAPs.Results Human iPSCs expressed the pluripotency markers OCT4,SOX2,Nanog,and SSEA1 and were positive for alkaline phosphatase staining.The hiPSCs-NECs were obtained on day 13 in the form of neural rosettes expressing neuroepithelial markers SOX2,nestin,and PAX6.In digested hiPSCs-NECs,the addition of 5 μmol/L Y27632 significantly promoted survival of the adherent cells,increased cell viability and the proportion of S-phase cells(P<0.01),and reduced the rate of apoptotic cells(P<0.05).On day 28 of induction,the obtained cells highly expressed the specific markers of DAPS(TH,FOXA2,NURR1,and Tuj1).Conclusion Treatment with Y27632(5 μmol/L)for 24 h significantly promotes the survival of human iPSCs-NECs during their differentiation into DPAs without affecting the cell differentiation,which indirectly enhances the efficiency of cell differentiation.

Objective:We aimed to analyse the trend of incidence and mortality of stomach cancer in Shandong province from 2012 to 2022 and predict the development trend from 2023 to 2030.Methods:Data on incidence and mortality of stomach cancer in Shandong province from 2012 to 2022 were obtained from Shandong Cancer Registry. The incidence, age-specific incidence, mortality and age-specific mortality in different years, sexes and urban and rural areas were calculated, the rates were standardized based on the age composition of the Chinese standard population in 2000. The average annual percent change (AAPC) of incidence and mortality was calculated using Joinpoint software. The Bayesian age-period-cohort model was used to predict the trend of stomach cancer incidence and mortality from 2023 to 2030.Results:From 2012 to 2022, the stomach cancer age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) showed a decreasing trend. The ASIR decreased from 27.47/100 000 in 2012 to 16.06/100 000 in 2022 (AAPC=-5.10%, P＜0.001), and the ASMR decreased from 17.69/100 000 to 11.09/100 000 (AAPC=-5.52%, P＜0.001). The ASIR and ASMR of male, female, urban and rural population also showed downward trends. The incidence and mortality rates of men were always higher than those of women, and the difference between urban and rural areas is gradually narrowing. In 2022, the ASIR (16.09/100 000 in urban and 16.03/100 000 in rural) and the ASMR (11.10/100 000 in urban and 11.08/100 000 in rural) of stomach cancer between urban and rural areas were nearly identical. The Bayesian age-period-cohort model predicted that the ASIR of stomach cancer in Shandong would further decrease from 2023 to 2030 (AAPC=-0.51%, P=0.001), but the change tended to be smooth. The incidences in male (AAPC=-1.46%, P=0.010) and rural areas (AAPC=-1.21%, P＜0.001) were still expected to have a little room for decline. The trend of incidences in female and urban areas were not statistically significant. The trend of mortality was consistent with the incidence. Conclusions:The stomach cancer incidence and mortality in Shandong shows a decreasing trend and it is expected to decrease further by 2030. However, the trend tends to be smooth, and the disease burden should be reduced as early as possible for high-risk population and high-risk factors of stomach cancer.

Objective To investigate the feasibility of using contrast-enhanced T1WI radiomics in predicting the pathological grade in rectal adenocarcinoma.Methods The MRI and pathological data of 127 patients with rectal adenocarcinoma were analyzed retrospectively.ITK-SNAP software was used to manually draw region of interest(ROI)in rectal cancer on axial T,WI enhanced images.The radiomics features were extracted by the Pyradiomics software from ROI.The task was divided into two parts:task 1("high & non-high"group)predicted the high-differentiation and moderate/low-differentiation of the tumor;task 2("moderate & low"group)predicted the tumor's moderate-differentiation and low-differentiation in"non-high"group.Maximum relevance and minimum redundancy(mRMR)method was used to screen features.The five methods including least absolute shrinkage and selection operator(LASSO),logistic regression(LR),naive Bayes(NB),random forest(RF),and support vector machine(SVM)were used to build the models,and the efficiency of each model was evaluated and compared.Results In task 1,the area under the curve(AUC)of five methods were 0.86,0.90,0.59,1.00,0.99 in the training cohort and 0.71,0.62,0.53,0.67,0.64 in the testing cohort.In task 2,the AUC of five methods in the training cohort were 0.93,0.85,0.67,0.92,0.89,and in the testing cohort were 0.86,0.80,0.50,0.78,0.71.The models constructed by LASSO in both tasks were the dominant models,the AUC of the fusion model in the testing cohort which combined with age,gender and the dominant Radiomics score(Radscore)was 0.80[95％confidence interval(CI)0.63-0.96]in task 1,and the accuracy,sensitivity and specificity were 78.94％,77.78％,and 79.31％respectively.They were 0.89(95％CI 0.74-1.00),90.00％,95.65％,and 71.43％,respectively in task 2.The calibration curves showed that the fusion models had a good goodness of fit.Conclusion Based on the establishment of two dichotomous models,the radiomics based on the contrast-enhanced T1 WI is feasible in predicting the high,moderate and low differentiation degree of rectal adenocarcinoma.