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Tongxinluo Activates PI3K/AKT Signaling Pathway to Inhibit Endothelial Mesenchymal Transition and Attenuate Myocardial Fibrosis after Ischemia-Reperfusion in Mice

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Chinese Journal of Integrative Medicine 2024年第7期30卷 608-615页

作者： WEI Ya-ru HOU Yun-long YIN Yu-jie LI Zhen LIU Yi han ning-xin WANG Zi-xuan LIU Lu WANG Xiao-qi HAO Yuan-jie MA Kun GU Jiao-jiao JIA Zhen-hua Graduate School Hebei University of Chinese Medicine Shijiazhuang Yiling Pharmaceutical New Drug Evaluation Center Hebei Institute of Integrated Traditional and Western Medicine National Key Laboratory for Innovation and Transformation of Luobing Theory Department of Cardiology Hebei Yiling Hospital Graduate School Hebei Medical University

Objective: To investigate the potential role of Tongxinluo(TXL) in attenuating myocardial fibrosis after myocardial ischemia-reperfusion injury(MIRI) in mice. Methods: A MIRI mouse model was established by left anterior descending coronary artery ligation for 45 min. According to a random number table, 66 mice were randomly divided into 6 groups(n=11 per group): the sham group, the model group, the LY-294002 group, the TXL group, the TXL+LY-294002 group and the benazepril(BNPL) group. The day after modeling, TXL and BNPL were administered by gavage. Intraperitoneal injection of LY-294002 was performed twice a week for 4 consecutive weeks. Echocardiography was used to measure cardiac function in mice. Masson staining was used to evaluate the degree of myocardial fibrosis in mice. Qualitative and quantitative analysis of endothelial mesenchymal transition(EndMT) after MIRI was performed by immunohistochemistry, immunofluorescence staining and flow cytometry, respectively. The protein expressions of platelet endothelial cell adhesion molecule-1(CD31), α-smoth muscle actin(α-SMA), phosphatidylinositol-3-kinase(PI3K) and phospho protein kinase B(p-AKT) were assessed using Western blot. Results: TXL improved cardiac function in MIRI mice, reduced the degree of myocardial fibrosis, increased the expression of CD31 and inhibited the expression of α-SMA, thus inhibited the occurrence of EndMT(P0.05). In addition, the use of the PI3K/AKT pathway-specific inhibitor LY-294002 to block this pathway and combination with TXL intervention, eliminated the protective effect of TXL, further supporting the protective effect of TXL. Conclusion: TXL activated the PI3K/AKT signaling pathway to inhibit EndMT and attenuated myocardial fibrosis after MIRI in mice.

关键词： myocardial fibrosis endothelial mesenchymal transition myocardial ischemia-reperfusion injury phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) pathway

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Risk Factors of Depression Screened by Two-Sample Mendelian Randomization Analysis:A Systematic Review

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Biomedical and Environmental Sciences 2024年第1期37卷 85-95页

作者： WANG han Lin XUE Yan Feng CUI Bao Qiu LIU Hong SHEN xin xin Shandong Provincial Research Center for Bioinformatic Engineering and Technique School of Life SciencesShandong University of TechnologyZibo 255049ShandongChina Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical UniversityTaiyuan 030013ShanxiChina State Key Laboratory of Infectious Disease Prevention and Control National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China

Objective This study explored the potentially modifiable factors for depression and major depressive disorder(MDD)from the MR-Base database and further evaluated the associations between drug targets with MDD.Methods We analyzed two-sample of Mendelian randomization(2SMR)using genetic variant depression(n=113,154)and MDD(n=208,811)from Genome-Wide Association Studies(GWAS).Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 genomes.The MR analysis was performed by screening drug targets with MDD in the DrugBank database to explore the therapeutic targets for MDD.Inverse variance weighted(IVW),fixed-effect inverse variance weighted(FE-IVW),MR-Egger,weighted median,and weighted mode were used for complementary calculation.Results The potential causal relationship between modifiable risk factors and depression contained 459 results for depression and 424 for MDD.Also,the associations between drug targets and MDD showed that SLC6A4,GRIN2A,GRIN2C,SCN10A,and IL1B expression are associated with an increased risk of depression.In contrast,ADRB1,CHRNA3,HTR3A,GSTP1,and GABRG2 genes are candidate protective factors against depression.Conclusion This study identified the risk factors causally associated with depression and MDD,and estimated 10 drug targets with significant impact on MDD,providing essential information for formulating strategies to prevent and treat depression.

关键词： Risk factors Drug targets Depression Major depressive disorder Two-sample Mendelian randomization

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Effect of solvent on the initiation mechanism of living anionic polymerization of styrene:A computational study

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Chinese Journal of Chemical Engineering 2024年第5期69卷 135-142页

作者： Shen Li Yin-ning Zhou Zhong-xin Liu Zheng-Hong Luo School of Chemical Engineering and Technology Hainan UniversityHaikou 570228China Department of Chemical Engineering School of Chemistry and Chemical EngineeringState Key Laboratory of Metal Matrix CompositesShanghai Jiao Tong UniversityShanghai 200240China

For living anionic polymerization(LAP),solvent has a great influence on both reaction mechanism and kinetics.In this work,by using the classical butyl lithium-styrene polymerization as a model system,the effect of solvent on the mechanism and kinetics of LAP was revealed through a strategy combining density functional theory(DFT)calculations and kinetic modeling.In terms of mechanism,it is found that the stronger the solvent polarity,the more electrons transfer from initiator to solvent through detailed energy decomposition analysis of electrostatic interactions between initiator and solvent molecules.Furthermore,we also found that the stronger the solvent polarity,the higher the monomer initiation energy barrier and the smaller the initiation rate coefficient.Counterintuitively,initiation is more favorable at lower temperatures based on the calculated results ofΔG_(TS).Finally,the kinetic characteristics in different solvents were further examined by kinetic modeling.It is found that in benzene and n-pentane,the polymerization rate exhibits first-order kinetics.While,slow initiation and fast propagation were observed in tetrahydrofuran(THF)due to the slow free ion formation rate,leading to a deviation from first-order kinetics.

关键词： Living anionic polymerization Solvent effect Reaction kinetics Computational chemistry Mathematical modeling Kinetic modeling

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Stepping forward:T-cell redirecting bispecific antibodies in cancer therapy

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2361-2377页

作者： Xiaojing Qin Wenjing ning han Liu Xue Liu Wenxin Luo ningshao Xia State Key Laboratory of Vaccines for Infectious Diseases Xiang An Biomedicine LaboratorySchool of Public HealthXiamen UniversityXiamen 361102China National Institute of Diagnostics and Vaccine Development in Infectious Diseases State Key Laboratory of Molecular Vaccinology and Molecular DiagnosticsNational Innovation Platform for IndustryeEducation Integration in Vaccine Researchthe Research Unit of Frontier Technology of Structural Vaccinology of Chinese Academy of Medical SciencesXiamen UniversityXiamen 361102China

T cell-redirecting bispecific antibodies are specifically designed to bind to tumor-associated antigens,thereby engaging with CD3 on the T cell receptor.This linkage between tumor cells and T cells actively triggers T cell activation and initiates targeted killing of the identified tumor cells.These antibodies have emerged as one of the most promising avenues within tumor immunotherapy.However,despite success in treating hematological malignancies,significant advancements in solid tumors have yet to be explored.In this review,we aim to address the critical challenges associated with T cellredirecting bispecific antibodies and explore novel strategies to overcome these obstacles,with the ultimate goal of expanding the application of this therapy to include solid tumors.

关键词： Bispecific antibody(BsAbs) T-cell redirecting BsAbs Tumor-associated antigens Toxicity Cytokine release syndrome Tumor microenvironment Cancer immunotherapy Combination therapy strategies

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Exosomes from umbilical cord mesenchymal stromal cells promote the collagen production of fibroblasts from pelvic organ prolapse

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World Journal of Stem Cells 2024年第6期16卷 708-727页

作者： Lei-Mei Xu xin-xin Yu ning Zhang Yi-Song Chen Department of Gynecology Obstetrics and Gynecology Hospital of Fudan UniversityShanghai 200011China Department of Gynecology Shanghai Key Laboratory of Female Reproductive Endocrine-related DiseasesShanghai 200011China

BACKGROUND Pelvic organ prolapse(POP)involves pelvic organ herniation into the vagina due to pelvic floor tissue laxity,and vaginal structure is an essential factor.In POP,the vaginal walls exhibit abnormal collagen distribution and decreased fibroblast levels and functions.The intricate etiology of POP and the prohibition of trans-vaginal meshes in pelvic reconstruction surgery present challenges in targeted therapy development.Human umbilical cord mesenchymal stromal cells(hucMSCs)present limitations,but their exosomes(hucMSC-Exo)are promising therapeutic tools for promoting fibroblast proliferation and extracellular matrix remodeling.suppressed inflammation in POP group fibroblasts,stimulated primary fibroblast growth,and elevated collagen I(Col1)production in vitro.High-throughput RNA-seq of fibroblasts treated with hucMSC-Exo and miRNA sequencing of hucMSC-Exo revealed that abundant exosomal miRNAs downregulated matrix metalloproteinase 11(MMP11)expression.CONCLUSION HucMSC-Exo normalized the growth and function of primary fibroblasts from patients with POP by promoting cell growth and Col1 expression in vitro.Abundant miRNAs in hucMSC-Exo targeted and downregulated MMP11 expression.HucMSC-Exo-based therapy may be ideal for safely and effectively treating POP.

关键词： Pelvic organ prolapse Exosomes Fibroblasts Human umbilical cord mesenchymal stromal cells Extracellular matrix Collagen I

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Clinical characteristics and treatment of splenic infarction in children with systemic lupus erythematosus

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World Journal of Pediatrics 2024年第5期20卷 525-531页

作者： Yan Li Yu-Rong Piao Tong-xin han Hua-Wei Mao Department of Immunology Ministry of Education Key Laboratory of Major Diseases in ChildrenBeijing Key Laboratory for Genetics of Birth DefectsNational Center for Children’s HealthBeijing Children’s HospitalCapital Medical UniversityNo.56 Nan Li Shi LuBeijing100045China

Splenic infarction(SI)is a rare clinical phenomenon that occurs when the blood supply to the spleen is interrupted,resulting in tissue ischemia and necrosis[1].There are many causes of SI;in adult patients,cardioembolism,hematological malignancy,and infectious disease are the most common[2].Rheumatic diseases,especially systemic lupus erythematosus(SLE)and granulomatosis with polyangitis,can also lead to SI[3];however,only a few cases have been reported.There are currently no statistically meaningful data on the etiology of SI in children.Although most patients with SI can recover after conservative treatment,a small number of patients develop complications,such as splenic abscess,splenic rupture,splenic hemorrhage,and hemoperitoneum,and may even undergo splenectomy in severe cases.

关键词： erythematosus lupus treatment

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Intestinal malrotation complicated with gastric cancer: A case report

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World Journal of Clinical Cases 2024年第1期12卷 210-216页

作者： Xiang-Hao Jia Shuai Kong xin-xin Gao Bi-Cong Cong Chun-ning Zheng School of Clinical Medicine Weifang Medical UniversityWeifang 261053Shandong ProvinceChina Department of Gastrointestinal Surgery Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250000Shandong ProvinceChina

BACKGROUND Intestinal malrotation is a congenital defect of embryonic development caused by various teratogenic factors.In this condition,the intestinal tube,along with the superior mesenteric artery serving as the axis for the counterclockwise movement,is incomplete or abnormally rotated due to incomplete attachment of the mesentery and abnormal intestinal tube position.Such a case is usually asymp-tomatic and thus difficult to detect.Therefore,similar variant malformations are only found during an operation required for other abdominal diseases.CASE SUMMARY An elderly male patient was admitted to the hospital due to gastric cancer.An abdominal computed tomography(CT)scan with contrast revealed that the ascending and descending colon were parallel on the right side of the abdominal cavity,while the sigmoid colon extended into the right iliac fossa,allowing the diagnosis of congenital midgut malrotation.Following thorough preoperative preparation,the patient underwent laparoscopic radical gastrectomy to treat his gastric cancer.Intraoperatively,an exploration of the abdominal cavity uncovered the absence of the transverse colon.The distal colon at the hepatic flexure,along with the ascending colon,extended into the right iliac fossa,where it continued as the sigmoid colon.As planned,the laparoscopic radical gastrectomy was perform-ed,and the patient was discharged from the hospital 7 d after the surgery.CONCLUSION Asymptomatic intestinal malrotation is best detected by CT,requiring no treatment but possibly interfering with the treatment of other diseases.

关键词： Intestinal malrotation Congenital malformation Gastric cancer Abdominal

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A Dietary Supplement Jinghuosu Ameliorates Reproductive Damage Induced by Tripterygium Glycosides

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Chinese Journal of Integrative Medicine 2024年第4期30卷 330-338页

作者： MA Jing SUN Bo TE Li-ger HUANG xin ZUO xin han Xiao-ke WANG Shu-song Hebei Key Laboratory of Reproductive Medicine Hebei Institute of Reproductive HealthHebei Reproductive Health HospitalShijiazhuang(050071)China Graduate School of Hebei Medical University Shijiazhuang(050017)China School of Chemistry and Materials Science Hebei Normal UniversityShijiazhuang(050024)China xingtai Infertility Specialist Hospital XingtaiHebei Province(054000)China

Objective To determine the possible protective effects of Jinghuosu,a dietary supplement(DS),on tripterygium glycosides(TG)-induced reproductive system injury in rats and its underlying mechanisms.Methods A reproductive damage model was established in rats by feeding of TGs.Twenty-eight male Sprague Dawley rats were randomly divided into 4 groups using a random number table(n=7 in each):control(C)group,model(M)group,DS group and L-carnitine(LC)group.Rats in M,DS and LC groups received 40 mg/kg TGs orally.Starting from the 5th week,after administration of TGs for 4 h every day,rats in DS and LC groups were administered with 2.7 g/kg DS and 0.21 g/kg LC,respectively,for protective treatment over the next 4 weeks.Rats in Group C continued to receive the control treatment.Hematoxylin-eosin staining was used for histopathological analysis of rat testicular tissues.Enzyme-linked immunosorbent assay was performed to measure alkaline phosphatase(ALP),lactate dehydrogenase,alcohol dehydrogenase,total antioxidant capacity(T-AOC),superoxide dismutase,glutathione peroxidase(GSH-Px),and malondialdehyde(MDA)concentrations.Chemiluminescence assay was used to determine the serum testosterone content.Quantitative real-time PCR and Western blotting were conducted to analyze the expression of genes and proteins related to the testosterone synthesis pathway and the nuclear factor erythroid 2-related factor 2/heme oxygenase 1 antioxidant pathway.Results Oral administration of TGs induced significant increases in the testicular levels of zinc transporter 1 and MDA(Phand,sperm concentration,sperm motility,and serum testosterone,serum zinc,testicular zinc,Zrt-,Irt-like protein 1,ALP,luteinizing hormone(LH)receptor,steroidogenic acute regulatory protein,Cytochrome P450 family 11 subfamily A member 1,3β-hydroxysteroid dehydrogenase 1 T-AOC,GSH-Px,nuclear factor erythroid 2-related factor 2,heme oxygenase-1 and NAD(P)H:quinone oxidoreductase 1 levels decreased following TGs exposure(P<0.05).All of these phenotypes were

关键词： dietary supplement Jinghuosu tripterygium glycosides reproductive damage infertility

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Effect of inflammatory response on joint function after hip fracture in elderly patients:A clinical study

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World Journal of Orthopedics 2024年第4期15卷 337-345页

作者： Jia-Ming Wang Yu-Tao Pan Chen-Song Yang Ming-Chong Liu Sheng-Chao Ji ning han Fang Liu Gui-xin Sun Department of Traumatic Surgery Shanghai East HospitalSchool of MedicineTongji UniversityShanghai 200092China

BACKGROUND Excellent hip joint function facilitates limb recovery and improves the quality of survival.This study aimed to investigate the potential risk factors affecting postoperative joint functional activity and outcomes in elderly hip fractures patients and to provide evidence for patient rehabilitation and clinical management.AIM To explore the relationship between inflammatory factors and hip function and the interaction between inflammation and health after hip fracture in elderly patients.METHODS The elderly patients who had hip fracture surgery at our hospital between January 1,2021,and December 31,2022 were chosen for this retrospective clinical investigation.Patients with excellent and fair postoperative hip function had their clinical information and characteristics gathered and compared.Age,gender,fracture site,surgical technique,laboratory indices,and other variables that could have an impact on postoperative joint function were all included in a univariate study.To further identify independent risk factors affecting postoperative joint function in hip fractures,risk factors that showed statistical significance in the univariate analysis were then included in a multiple logistic regression analysis.In addition to this,we also compared other outcome variables such as visual analogue scale and length of hospital stay between the two groups.RESULTS A total of 119 elderly patients with hip fractures were included in this study,of whom 37 were male and 82 were female.The results of univariate logistic regression analysis after excluding the interaction of various factors showed that there was a statistically significant difference in interleukin(IL)-6,IL-8,IL-10,C-reactive protein(CRP),and complement C1q(C1q)between the fair and excellent joint function groups(P20 pg/mL[Odds ratio(OR)3.070,95%CI:1.243-7.579],IL-8>21.4 pg/mL(OR 3.827,95%CI:1.498-9.773),CRP>10 mg/L(OR 2.142,95%CI:1.020-4.498)and C1q>233 mg/L(OR 2.339,95%CI:1.094-

关键词： Hip function Fracture Inflammatory factors Risk factors Prevention

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Multiplicity of solutions for the semilinear subelliptic Dirichlet problem

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Science China Mathematics 2024年第3期67卷 475-504页

作者： Hua Chen Hong-Ge Chen Jin-ning Li xin Liao School of Mathematics and Statistics Wuhan UniversityWuhan 430072China Wuhan Institute of Physics and Mathematics Innovation Academy for Precision Measurement Science and TechnologyChinese Academy of SciencesWuhan 430071China

In this paper,we study the semilinear subelliptic equation{−△Xu=f(x,u)+g(x,u)inΩ,u=0 on∂Ω,where△X=−∑m i=1 Xi∗Xi is the self-adjoint Hormander operator associated with the vector fields X=(X_(1),X_(2),...,X_(m))satisfying the Hormander's condition,f(x,u)∈C(Ω×R),g(x,u)is a Carathéodory function onΩ×R,andΩis an open bounded domain in R~n with smooth boundary.Combining the perturbation from the symmetry method with the approaches involving the eigenvalue estimate and the Morse index in estimating the minimax values,we obtain two kinds of existence results for multiple weak solutions to the problem above.Furthermore,we discuss the difference between the eigenvalue estimate approach and the Morse index approach in degenerate situations.Compared with the classical elliptic cases,both approaches here have their own strengths in the degenerate cases.This new phenomenon implies that the results in general degenerate cases would be quite different from the situations in classical elliptic cases.

关键词： degenerate elliptic equations Hormander operators perturbation method Morse index

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