Janus kinase 2（JAK2）/signal transducer and activator of transcription 3（STAT3） signaling pathway regulates multiple processes in neurons， including growth， development， proliferation and differentiation， and is closely associated with the onset， progression and treatment of cerebral ischemia-reperfusion injury （CIRI）. This article provides an overview of the JAK2/ STAT3 signaling pathway and its relationship with CIRI， followed by a comprehensive review of the current research status on the regulation of the JAK2/STAT3 signaling pathway by traditional Chinese medicine （TCM） to ameliorate CIRI. Among them， TCM monomers and compound prescriptions such as glycyrrhetinic acid， triptolide， and Taohong siwu decoction can inhibit inflammatory responses， enhance cellular autophagy， and suppress apoptosis by inhibiting the JAK2/STAT3 signaling pathway， thereby alleviating CIRI. In addition， TCM monomers and compound prescriptions like astragaloside Ⅳ， ginkgolide K， and Qingnao dripping pills can mitigate CIRI by activating the JAK2/STAT3 signaling pathway to inhibit oxidative stress， promote angiogenesis， and enhance neuronal survival rates.

BACKGROUND:Endothelial injury is one of the causes of cardiovascular diseases.Human induced pluripotent stem cells are easy to obtain,have strong differentiation ability,and have less exclusiveness,and their endothelial differentiated cells can be used as ideal cells for cardiovascular disease research. OBJECTIVE:To investigate the effect and mechanism of calycosin on endothelial differentiation of human induced pluripotent stem cells and to provide technical support for microvascular regeneration. METHODS:Human induced pluripotent stem cells were divided into control group and calycosin group(1.25,2.5 μg/mL),and growth factors were added to induce single-layer endothelial differentiation.After the induction of differentiation for 8 days,the positive rate of endothelial cell marker CD144 was detected by flow cytometry.Fluorescent expressions of CD144 and CD31 were detected by the immunofluorescence method.Lentivirus RNAi GFP puromycin was used to silence human-induced pluripotent stem cell Piezo1 mRNA followed by endothelial directed differentiation.After 8 days of differentiation,the positive rate of CD144 in differentiated cells was detected by flow cytometry.The mRNA expression levels of CD144,Piezo1 and MEK were detected by qPCR. RESULTS AND CONCLUSION:(1)Compared with the control group,the positive rate of CD144 was significantly increased in the 1.25 and 2.5 μg/mL calycosin groups(P<0.05).The expressions of CD144,Piezo1,and MEK mRNA were increased in the 2.5 μg/mL calycosin group(P<0.05).The fluorescence expressions of CD144(P<0.01)and CD31(P<0.001)were significantly increased in the 2.5 μg/mL calycosin group.(2)Compared with the shNT group,CD144 positive rate and CD144,Piezo1,MEK mRNA expressions were significantly increased in the shNT + calycosin 1.25,2.5 μg/mL groups(P<0.05).Compared with the shPiezo1 group,the positive rate of CD144 and mRNA expressions of CD144,Piezo1 and MEK had no significant changes in the shPiezo1+calycosin 1.25,2.5 μg/mL groups(P>0.05).(3)It is concluded that 2.5 μg/mL calycosin promotes the differentiation of human-induced pluripotent stem cells into endothelial lineages.Calycosin promotes the downstream MEK expression,thereby promoting the endothelial differentiation of human induced pluripotent stem cells by targeting the expression level of Piezo1.

AIM:To investigate whether crocin alleviates right ventricular injury induced by monocrotaline(MCT)in rats with pulmonary arterial hypertension(PAH),and to explore the underlying mechanisms.METHODS:Forty male SD rats were randomly divided into 4 groups:normal group,PAH group,crocin group and sildenafil group,with 10 rats in each group.The rats in PAH,crocin and sildenafil groups received subcutaneous injection of MCT(50 mg/kg)to establish the PAH model.Starting from the day of MCT injection,the rats in crocin group received crocin(200 mg/kg),the rats in sildenafil group received sildenafil(30 mg/kg),and those in PAH and normal groups were orally gavaged with an equal volume of saline once daily.After 4 weeks,measurements of right ventricular systolic pressure(RVSP),mean pulmonary artery pressure(mPAP),right ventricular hypertrophy index(RVHI)and right ventricular mass index(RVMI)were taken for the rats in each group.Tissue staining was conducted to observe pathological changes in the right ventricle,and the expression levels of inflammatory factors(IL-1β,IL-6 and TNF-α),the p38 MAPK/NF-κB inflammato-ry pathway,CCL2,CCR2,and the macrophage marker CD68 were assessed.RESULTS:Compared with PAH group,the rats in crocin and sildenafil groups exhibited significant reductions in RVSP,mPAP,RVHI and RVMI(P＜0.05).Right ventricular tissue displayed no evident infiltration of inflammatory cells or proliferation of collagen fibers.The down-regulation of the p38 MAPK/NF-κB pathway and inflammatory factors(IL-1β,IL-6 and TNF-α)was significant(P＜0.05).Additionally,the CCL2/CCR2 pathway and the infiltration of CD68+ macrophages were markedly decreased(P＜0.05).CONCLUSION:Crocin effectively mitigates right ventricular damage in MCT-induced PAH rats,with its effica-cy comparable to that of sildenafil at the dosage utilized in this experiment.Some protective mechanisms of crocin may be attributed to its regulatory effects on inflammation.

OBJECTIVE To analyze the use status and development trend of proton pump inhibitors(PPIs) in 33 hospitals in Wuhan, Hubei Province after the implementation of the national centralized drug procurement(NCDP) policy, and to provide reference for promoting the subsequent rational use of NCDP drugs and improving related policies. METHODS To make statistics and analysis of purchasing amount of PPIs, defined daily dose system(DDDs), defined daily dose consumption(DDDc) and utilization rate of 33 hospitals in Wuhan in 2019 and 2022. RESULTS After the implementation of the NCDP policy, the total purchasing amount of PPIs decreased by 53.6%, DDDs decreased by 15.4%, DDDc decreased by 45.2%, and the utilization rate of PPIs injectable dosage forms decreased by 12.6%. After NCDP, the highest growth rate of oral dosage forms was omeprazole(5.7%), followed by rabeprazole(5.0%), while injectable dosage forms showed a significant difference in utilization rate, with a significant decline in NCDP varieties and a significant increase in non-NCDP varieties. The overall NCDP utilization rate of PPIs in Wuhan was 64.9%, with little difference among hospitals of different grades. CONCLUSION The NCDP policy achieves the purpose of reducing the drug cost of patients and improving the accessibility of drugs, and is more optimized in the selection of dosage forms, which is in line with the policy expectations overall; but the quantity and price of PPIs in Wuhan decreased after NCDP, and highlighted a certain tendency in the selection of varieties. In the future, we still need to optimize measures to guide clinical priority in the selection of NCDP drugs, to ensure and improve the implementation of NCDP policy.

Objective:To explore the efficacy of online pulmonary rehabilitation (PR) management among community-dwelling patients with stable chronic obstructive pulmonary disease (COPD).Methods:This study was a single-center randomized controlled trail with an unblinded design. A total of 130 patients with stable COPD who visited Zhuanqiao Community Health Service Center in Shanghai Minhang District from October 2020 to March 2022 were randomly divided into study group and control group with 65 cases in each group. Both groups received conventional treatment, while patients in study group attended online rehabilitation management, including face-to-face rehabilitation instruction and multiple online guidance. Pulmonary ventilation function including forced vital capacity (FVC), forced expiratory volume in the first second (FEV 1) and percentage of forced expiratory volume in the first second to forced expiratoty volume (FEV 1%pred), modified British Medical Research Council Dyspnea Scale (mMRC), chronic obstructive pulmonary disease assessment test (CAT), score of 6 minutes walking distance (6MWD) and DOSE (dyspnea, degree of airflow obstruction, smoking status, the number of exacerbation) index were measured at baseline and after 8 weeks of rehabilitation, and compared between two groups. Results:The baseline data of the two groups were comparable. After 8 weeks of management, FVC, FEV 1, FEV 1%pred, mMRC, CAT, 6MWD and DOSE index of both groups were improved compared with the baseline level(control group: t=-7.799, -7.581, -9.010, 3.565, 9.887, -16.677, 3.795; study group: t=-12.623, -13.914, -17.644, 7.404, 22.457, -26.826, 7.968; all P<0.05). The FEV 1%pred, CAT and 6MWD in the study group were better than those in the control group ( t=-2.939, 2.277,-2.130, all P<0.05); while there were no significant differences in FVC, FEV 1, mMRC and DOSE index between the two groups( t=-0.162, -1.280, 0.925, 1.939,all P>0.05). Conclusions:The online pulmonary rehabilitation management can better improve lung function, dyspnea symptoms and exercise tolerance of patients with stable COPD, which can be used for rehabilitation training and management of community-dwelling patients.

Peripheral T-cell lymphoma (PTCL) is a relatively common subtype of non-Hodgkin lymphomain in China. PTCL is clinically highly aggressive, and it progresses rapidly. The current treatment methods are ineffective and the overall prognosis is poor, especially in patients with relapsed and/or refractory. In recent years, the treatment of phosphatidylinositol 3-kinase (PI3K) inhibitors has developed rapidly, which can effectively improve the prognosis of patients with relapsed and/or refractory PTCL. This article reviews the therapeutic mechanism, effectiveness and safety of PI3K inhibitors in the treatment of relapsed and/or refractory PTCL.

Objective:To compare the short-term efficacy of drug-coated balloon and common balloon in the treatment of with below-the-ankle arteriosclerosis obliterans (ASO).Methods:The clinical and follow-up data of 115 patients (118 limbs) with lower extremity ASO of Rutherford 4-6 admitted to the Department of Peripheral Vascular Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences from Jun 2021 to Jun 2023 were retrospectively analyzed.Results:Patients were divided into group of 52 limbs using paclitaxel-coated balloon and group of 66 limbs using common balloon. During the 6-month follow-up period, The total effective rate of wound surface was 98.1% in the drug-coated balloon group and 92.4% in the common balloon group. The difference was statistically significant ( P<0.05); the increase of ankle-brachial index (ABI) and toe-brachial index (TBI) in the drug-coated balloon group were significantly better than common balloon group, and the difference was statistically significant ( P<0.01). No major adverse events occurred in the two groups during the 6-month follow-up period. Compared with the common balloon group, the drug-coated balloon group had a higher limb salvage rate (100.0% vs. 98.5% ) and a lower target vessel reconstruction rate (7.7% vs.18.2%), though the difference was not statistically significant ( P>0.05). Conclusion:Compared with the common balloon, the drug-coated balloon is more effective in the treatment of patients with wound healing rate and vascular patency rate in Rutherford 4-6 grade below-the-ankle artery lesions.

Objective:To discuss the effects of monocyte chemoattractant protein-1(MCP-1)on the migration and invasion of lung cancer A549 cells,and to clarify the mechanisms.Methods:Immunohistochemistry method was used to detect the expression of MCP-1 protein in 80 cases of non-small cell lung cancer(NSCLC)and adjacent normal lung tissues.The human lung cancer A549 cells were cultured in vitro.The MCP-1-small interfering RNA(siRNA)experiment was divided into blank group,negative control group(si-NC group),MCP-1-siRNA-1 group,and MCP-1-siRNA-2 group.The MCP-1 over-expression experiment was divided into control group,empty vector control group(OE-NC,transfected with MCP-1 over-expression empty vector),over-expression MCP-1 group(OE-MCP-1 group,transfected with MCP-1 over-expression plasmid),over-expression MCP-1+extracellular regulated protein kinase(ERK)pathway inhibitor PD98059 group(OE-MCP-1+PD98059 group,co-transfected with MCP-1 over-expression plasmid and PD98059),and PD98059 group(transfected with PD98059).The MCP-1 siRNA and plasmids were transfected into the lung cancer A549 cells;Western blotting method was used to verify the transfection efficiencies of the cells in various groups;the migration rate and the number of invasion cells in various groups were observed by wound healing assay and Transwell chamber assay,respectively;Western blotting method was also used to detect the expression levels of phosphorylated ERK(p-ERK),total ERK(t-ERK),and epithelial-mesenchymal transition(EMT)-related proteins in the A549 cells in various groups.Results:Compared with adjacent tissue,the positive expression rate of MCP-1 protein in NSCLC tissue was significantly increased(P<0.05),and the expression level of MCP-1 protein was related to TNM stage and lymph node metastasis(P<0.05).Compared with si-NC group,the expression level of MCP-1 protein in the cells in MCP-1-siRNA-1 and MCP-1-siRNA-2 groups was significantly decreased(P<0.01).Compared with control group and OE-NC group,the expression level of MCP-1 protein in the cells in OE-MCP-1 group was significantly increased(P<0.01).The wound healing assay results showed that compared with si-NC group,the migration rate of the cells in MCP-1-siRNA-1 and MCP-1-siRNA-2 groups were significantly decreased(P<0.01).Compared with OE-NC group,the migration rate of the cells in OE-MCP-1 group was significantly increased(P<0.01);compared with OE-MCP-1 group,the migration rate of the cells in OE-MCP-1+PD98059 group was significantly decreased(P<0.01).Compared with OE-MCP-1+PD98059 group,the migration rate of the cells in PD98059 group was significantly decreased(P<0.01).The Transwell chamber assay results showed that compared with si-NC group,the number of invasion cells in MCP-1-siRNA-1 and MCP-1-siRNA-2 groups was significantly decreased(P<0.01).Compared with OE-NC group,the number of invasion cells in OE-MCP-1 group was significantly increased(P<0.01);compared with OE-MCP-1 group,the number of invasion cells in OE-MCP-1+PD98059 group was significantly decreased(P<0.01);compared with OE-MCP-1+PD98059 group,the number of invasion cells in PD98059 group was significantly decreased(P<0.01).The Western blotting results showed that compared with si-NC group,the expression levels of p-ERK,Vimentin,and N-cadherin protein in the cells in MCP-1-siRNA-1 and MCP-1-siRNA-2 groups were significantly decreased(P<0.05 or P<0.01),and the expression level of E-cadherin proteins was significantly increased(P<0.01).Compared with OE-NC group,the expression levels of p-ERK,Vimentin,and N-cadherin proteins in the cells in OE-MCP-1 group were significantly increased(P<0.01),and the expression level of E-cadherin protein was significantly decreased(P<0.01).Compared with OE-MCP-1 group,the expression levels of p-ERK,Vimentin,and N-cadherins proteins in the OE-MCP-1+PD98059 group were significantly decreased(P<0.01),and the expression level of E-cadherin protein was significantly increased(P<0.05).Compared with OE-MCP-1+PD98059 group,the expression levels of p-ERK,Vimentin,and N-cadherin proteins in the cells in PD98059 group were significantly decreased(P<0.05 or P<0.01),and the expression level of E-cadherin protein was increased(P<0.01).Conclusion:MCP-1 protein can upregulate the expression of EMT-related proteins in the lung cancer A549 cells,and promote the migration and invasion of the lung cancer A549 cells;its mechanism may be related to the activation of the ERK signaling pathway.

Objective To observe the interventional effects of complex probiotic powder on blood bio-chemical indices and vaginal flora in pregnant women with high risk of gestational diabetes mellitus(GDM). Methods One hundred and ten pregnant women with high risk of GDM recruited from the outpatient clinics of the obstetric department and nutrition department in this hospital were randomly divided into the probiotic intervention group (n=55) and the placebo control group (n=55).The intervention group was given 1 bag of complex probiotic powder per day,and the control group was given 1 bag of placebo powder.The colors,shapes,sizes and tastes of powders in the two groups remained the consistency.The intervention duration in this trial was 23 weeks.The questionnaire survey were conducted at baseline and at the intervention endpoint,and the blood biochemical indexes detections were performed at baseline,after 24-28 weeks of gestation,and after 34-38 weeks of gestation,respectively.In addition,the differences in the composition of the vaginal flora structure between the two groups of high risk pregnant women with GDM were detected at the intervention endpoint.Results A total of 97 cases were eventually included in the statistical analysis.Among them,there were 50 cases in the probiotic intervention group and 47 cases in the placebo control group.At the end of the 23 week intervention,there were no statistically significant differences in fasting blood glucose,red blood cells,hemoglobin,leukocytes,ferritin,total protein,albumin,glutamic transaminase,glutamic oxalate transam-inase and total bilirubin between the probiotic intervention group and placebo control group (P>0.05).In terms of vaginal flora,there was a significant difference in some indicators of α diversity between the probiotic group and placebo control group (P<0.05),and there was no significant difference in β diversity between the two groups (P>0.05).At the level of vaginal flora phyla,there were significant differences in the Firmicutes,Actinobacteria,Desulfobacterota,Deferribacterota,and δ-Myxococcota between the two groups (P<0.05).At the level of vaginal flora genera,the relative abundance of Lactobacillus spp.in the probiotic intervention group was significantly higher than that in the control group (P<0.05).Conclusion Complex probiotic pow-der supplementation may have a limited role in improving blood glucose and other related biochemical indica-tors in high-risk pregnant women with GDM.But it has a certain role in regulating the vaginal micro ecological balance in pregnant women with high risk of GDM.

Epilepsy is a common, chronic neurological disorder that has been associated with impaired neurodevelopment and immunity. The chemokine receptor CXCR5 is involved in seizures via an unknown mechanism. Here, we first determined the expression pattern and distribution of the CXCR5 gene in the mouse brain during different stages of development and the brain tissue of patients with epilepsy. Subsequently, we found that the knockdown of CXCR5 increased the susceptibility of mice to pentylenetetrazol- and kainic acid-induced seizures, whereas CXCR5 overexpression had the opposite effect. CXCR5 knockdown in mouse embryos via viral vector electrotransfer negatively influenced the motility and multipolar-to-bipolar transition of migratory neurons. Using a human-derived induced an in vitro multipotential stem cell neurodevelopmental model, we determined that CXCR5 regulates neuronal migration and polarization by stabilizing the actin cytoskeleton during various stages of neurodevelopment. Electrophysiological experiments demonstrated that the knockdown of CXCR5 induced neuronal hyperexcitability, resulting in an increased number of seizures. Finally, our results suggested that CXCR5 deficiency triggers seizure-related electrical activity through a previously unknown mechanism, namely, the disruption of neuronal polarity.
Animals ; Humans ; Mice ; Actin Cytoskeleton/metabolism* ; Actins/metabolism* ; Epilepsy/metabolism* ; Neurons/metabolism* ; Receptors, CXCR5/metabolism* ; Seizures/metabolism*