Objective To investigate the effects of adiponectin(APN)on the proliferation,migration,and invasion of ovarian cancer cells and its potential association with the phosphatidylinositol 3-kinase(PI3K)/pro-tein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling pathway.Methods A2780 and SK-OV3 cell lines were selected.AdipoR1 mRNA expression was detected by real-time polymerase chain reaction(RT-PCR).The CCK-8 assay was employed to evaluate APN-induced proliferation,while scratch wound heal-ing and Transwell assays were conducted to assess migration and invasion capabilities.Western blot analysis was performed to measure the expression levels of PI3K,Akt,mTOR,and their phosphorylated forms(p-Akt,p-mTOR)at different time points(0-60 min)after APN treatment and across intervention groups(APN,LY294002,APN+LY294002).Results Both A2780 and SKOV3 cells expressed AdipoR1 mRNA.Compared with the control group,APN significantly enhanced the proliferation,migration,and invasion of o-varian cancer cells(P＜0.05).Under the stimulation of APN,the expression levels of p-Akt and p-mTOR in A2780 and SKOV3 cells showed a significant upward trend.The peak expression of p-Akt and p-mTOR in A2780 cells was observed at 30 minutes,while in SKOV3 cells,it occurred at 60 minutes.The expression lev-els of p-Akt and p-mTOR were significantly reduced in the LY294002 group and APN+LY294002 group(P＜0.001).Conclusion APN enhances the proliferation,migration,and invasion behavior of ovarian cancer cells by activating the PI3K/Akt/mTOR signaling pathway,and its effect can be reversed by PI3K inhibitors,providing a theoretical basis for targeted intervention in ovarian cancer progression.

ObjectiveThis study aims to explore the mechanism and targets of Shenfu Injection in regulating glycolysis to intervene in myocardial fibrosis in chronic heart failure based on the hypoxia-inducible factor-1α （HIF-1α）/ 6-phosphofructo-2-kinase/fructose-2，6-bisphosphatase 3 （PFKFB3） signaling pathway. MethodsA rat model of chronic heart failure was established by subcutaneous injection of isoproterenol （ISO）. After successful modeling， the rats were randomly divided into the Sham group， Model group， Shenfu injection （SFI， 6 mL·kg^-1） group， and inhibitor （3PO， 35 mg·kg^-1） group， according to a random number table， and they were treated for 15 days. Cardiac function was evaluated by echocardiography， and serum N-terminal pro-brain natriuretic peptide （NT-proBNP） levels were detected by enzyme-linked immunosorbent assay （ELISA）. Fasting body weight and heart weight were measured， and the heart index （HI） was calculated. Pathological changes in myocardial tissue were observed by hematoxylin-eosin （HE） and Masson staining， and the fibrosis rate was calculated. Biochemical assays were used to determine serum levels of glucose （GLU）， lactic acid （LA）， and pyruvic acid （PA）. Western blot was used to analyze the expression of proteins related to the HIF-1α/PFKFB3 signaling pathway （HIF-1α and PFKFB3）， glycolysis-related proteins （HK1， HK2， PKM2， and LDHA）， and fibrosis-related proteins ［transforming growth factor （TGF）-β₁， α-smooth muscle actin （α-SMA）， and Collagen type Ⅰ α1 （ColⅠA1）］. Real-time PCR was used to detect the mRNA expression of HIF-1α and PFKFB3 in myocardial tissue. ResultsCompared with the Sham group， the Model group showed significantly decreased left ventricular ejection fraction （LVEF）， left ventricular shortening fraction （LVFS）， interventricular septal thickness （IVSd）， and interventricular septal strain （IVSs） （P<0.05）， while left ventricular internal dimension at end-diastole （LVDd） and end-systole （LVIDs） were increased （P<0.05）. Serum NT-proBNP levels were significantly increased （P<0.01）， and body weight was decreased. Heart weight was increased， and the HIT index was increased （P<0.05）. Myocardial tissue exhibited inflammatory cell infiltration and collagen fiber deposition， and the fibrosis rate was significantly increased （P<0.05）. Serum GLU was decreased （P<0.05）， while LA and PA levels were increased （P<0.05）. Protein expressions of HIF-1α， PFKFB3， HK1， HK2， PKM2， LDHA， TGF-β₁， α-SMA， and ColⅠA1， as well as the mRNA expression of HIF-1α and PFKFB3 were increased （P<0.05）. Compared with the Model group， both the SFI group and 3PO groups showed significant improvements in LVEF， LVFS， IVSd， and IVSs （P<0.05） and decreases in LVDd， LVIDs， and NT-proBNP levels （P<0.05）. Body weight was significantly increased. Heart weight was significantly decreased， and the HIT index was significantly decreased （P<0.05）. Inflammatory cell infiltration， collagen fiber deposition， and the fibrosis rate were significantly decreased （P<0.05）. Serum GLU levels were significantly increased （P<0.05）， while LA and PA levels were decreased （P<0.05）. Expressions of glycolysis-related proteins， fibrosis-related proteins， and HIF-1α/PFKFB3 pathway-related proteins and mRNAs were significantly suppressed （P<0.05）. ConclusionSFI improves cardiac function in chronic heart failure by downregulating the expression of HIF-1α/PFKFB3 signaling pathway-related proteins， regulating glycolysis， and inhibiting myocardial fibrosis.

Objective:To investigate effect of artesunate(ART)on high glucose(HG)induced trophoblast cell damage and its mechanism.Methods:Human trophoblast cells HTR-8/SVneo were separated into control group,HG group,ART low concentra-tion group,ART high concentration group and ART high concentration+lysophosphatidic acid(LPA)group.CCK-8 method was applied to detect cell viability.Flow cytometry was applied to detect cell apoptosis.ELISA was applied to detect levels of TNF-α,IL-1β and IL-10.Reagent kits were used to detect levels of lactate dehydrogenase(LDH),malondialdehyde(MDA)and superoxide dismutase(SOD).Western blot was applied to detect expressions of Bax,Bcl-2,Ras homolog gene family member A(RhoA),Rho associated coiled coil containing protein kinase(ROCK)1 and ROCK2.Results:After treatment with 0.4～1.6 μmol/L ART,activity of HTR-8/SVneo cells were increased(P<0.05).ART greatly enhanced activity of HTR-8/SVneo cells induced by HG,and cell viability was most significantly increased under 1.6 μmol/L ART treatment(P<0.05).Compared with control group,activity of HTR-8/SVneo cells,IL-10,SOD and Bcl-2 levels were reduced in HG group,apoptosis rate,TNF-α,IL-1β,LDH,MDA,Bcl-2,RhoA,ROCK1 and ROCK2 levels were increased(P<0.05).Compared with HG group,activity of HTR-8/SVneo cells,IL-10,SOD and Bcl-2 levels were increased in ART low and high concentration groups,apoptosis rate,TNF-α,IL-1β,LDH,MDA,Bcl-2,RhoA,ROCK1 and ROCK2 levels were decreased(P<0.05).Compared with ART high concentration group,activity of HTR-8/SVneo cells,IL-10,SOD and Bcl-2 levels were decreased in ART high concentration+LPA group,apoptosis rate,TNF-α,IL-1β,LDH,MDA,Bcl-2,RhoA,ROCK1 and ROCK2 levels were increased(P<0.05).Conclusion:ART can inhibit inflammatory response and oxidative stress of trophoblast cells and reduce cell apoptosis,whose mechanism may be related to inhibition of RhoA/ROCK signaling pathway.

Objective:To explore facilitators and impediments to home glucose management for patients undergoing bariatric surgery based on the consolidated framework for implementation research (CFIR), so as to inform the development of a glucose management pathway after bariatric surgery.Methods:This study was a descriptive phenomenological study. Using purposive sampling method, seven healthcare professionals and 11 patients undergoing bariatric surgery from the General Surgery·Metabolic and Bariatric Center of China-Japan Friendship Hospital were selected from November 2023 to January 2024 for semi-structured interviews. Targeted content analysis was used for the data analysis.Results:A total of six facilitators and six impediments related to the five dimensions of CFIR were distilled. Facilitators included the personalized glucose management program, regular long-term follow-up, multidisciplinary management team, support from family and friends, complication distress, and information technology platform. Impediments involved patterned follow-up, poor accessibility and convenience of resources, role conflict, herd mentality, poor behavioral compliance, and low utilization of digital equipment.Conclusions:Glucose management needs vary in patients after bariatric surgery, with a gradual decline in management compliance. Healthcare professionals should build an "Internet +"home glucose management service model, carry out targeted multidisciplinary team follow-up, and promote the formation of a standardized pathway for patients' home glucose management.

Objective:To investigate effect of artesunate(ART)on high glucose(HG)induced trophoblast cell damage and its mechanism.Methods:Human trophoblast cells HTR-8/SVneo were separated into control group,HG group,ART low concentra-tion group,ART high concentration group and ART high concentration+lysophosphatidic acid(LPA)group.CCK-8 method was applied to detect cell viability.Flow cytometry was applied to detect cell apoptosis.ELISA was applied to detect levels of TNF-α,IL-1β and IL-10.Reagent kits were used to detect levels of lactate dehydrogenase(LDH),malondialdehyde(MDA)and superoxide dismutase(SOD).Western blot was applied to detect expressions of Bax,Bcl-2,Ras homolog gene family member A(RhoA),Rho associated coiled coil containing protein kinase(ROCK)1 and ROCK2.Results:After treatment with 0.4～1.6 μmol/L ART,activity of HTR-8/SVneo cells were increased(P<0.05).ART greatly enhanced activity of HTR-8/SVneo cells induced by HG,and cell viability was most significantly increased under 1.6 μmol/L ART treatment(P<0.05).Compared with control group,activity of HTR-8/SVneo cells,IL-10,SOD and Bcl-2 levels were reduced in HG group,apoptosis rate,TNF-α,IL-1β,LDH,MDA,Bcl-2,RhoA,ROCK1 and ROCK2 levels were increased(P<0.05).Compared with HG group,activity of HTR-8/SVneo cells,IL-10,SOD and Bcl-2 levels were increased in ART low and high concentration groups,apoptosis rate,TNF-α,IL-1β,LDH,MDA,Bcl-2,RhoA,ROCK1 and ROCK2 levels were decreased(P<0.05).Compared with ART high concentration group,activity of HTR-8/SVneo cells,IL-10,SOD and Bcl-2 levels were decreased in ART high concentration+LPA group,apoptosis rate,TNF-α,IL-1β,LDH,MDA,Bcl-2,RhoA,ROCK1 and ROCK2 levels were increased(P<0.05).Conclusion:ART can inhibit inflammatory response and oxidative stress of trophoblast cells and reduce cell apoptosis,whose mechanism may be related to inhibition of RhoA/ROCK signaling pathway.

Objective:To explore facilitators and impediments to home glucose management for patients undergoing bariatric surgery based on the consolidated framework for implementation research (CFIR), so as to inform the development of a glucose management pathway after bariatric surgery.Methods:This study was a descriptive phenomenological study. Using purposive sampling method, seven healthcare professionals and 11 patients undergoing bariatric surgery from the General Surgery·Metabolic and Bariatric Center of China-Japan Friendship Hospital were selected from November 2023 to January 2024 for semi-structured interviews. Targeted content analysis was used for the data analysis.Results:A total of six facilitators and six impediments related to the five dimensions of CFIR were distilled. Facilitators included the personalized glucose management program, regular long-term follow-up, multidisciplinary management team, support from family and friends, complication distress, and information technology platform. Impediments involved patterned follow-up, poor accessibility and convenience of resources, role conflict, herd mentality, poor behavioral compliance, and low utilization of digital equipment.Conclusions:Glucose management needs vary in patients after bariatric surgery, with a gradual decline in management compliance. Healthcare professionals should build an "Internet +"home glucose management service model, carry out targeted multidisciplinary team follow-up, and promote the formation of a standardized pathway for patients' home glucose management.

Interactions between brain-resident and peripheral infiltrated immune cells are thought to contribute to neuroplasticity after cerebral ischemia. However, conventional bulk sequencing makes it challenging to depict this complex immune network. Using single-cell RNA sequencing, we mapped compositional and transcriptional features of peri-infarct immune cells. Microglia were the predominant cell type in the peri-infarct region, displaying a more diverse activation pattern than the typical pro- and anti-inflammatory state, with axon tract-associated microglia (ATMs) being associated with neuronal regeneration. Trajectory inference suggested that infiltrated monocyte-derived macrophages (MDMs) exhibited a gradual fate trajectory transition to activated MDMs. Inter-cellular crosstalk between MDMs and microglia orchestrated anti-inflammatory and repair-promoting microglia phenotypes and promoted post-stroke neurogenesis, with SOX2 and related Akt/CREB signaling as the underlying mechanisms. This description of the brain's immune landscape and its relationship with neurogenesis provides new insight into promoting neural repair by regulating neuroinflammatory responses.
Humans ; Ischemic Stroke ; Brain/metabolism* ; Macrophages ; Brain Ischemia/metabolism* ; Microglia/metabolism* ; Gene Expression Profiling ; Anti-Inflammatory Agents ; Neuronal Plasticity/physiology* ; Infarction/metabolism*

Objective:To explore the differences of gene expression profiles of precursors of exhausted T cells (Tpex) and terminal exhausted T cells (Tex) in the peripheral blood of patients with active pulmonary tuberculosis (ATB).Methods:Twenty-five cases of ATB, 13 cases of latent tuberculosis infection (LTBI) and 10 health controls were enrolled from January 2021 to October 2022 in the Fifth People′s Hospital of Wuxi. The proportions of Tpex and Tex in the peripheral blood mononuclear cells (PBMCs) of the three groups were detected by flowcytometry. PBMCs of ATB were separated into Tpex and Tex by fluorescence-activated cell sorting. RNA-sequencing was performed and up-regulated and down-regulated genes were screended. Differently expressed genes were analyzed by gene set enrichment analysis of gene ontology (GO) to find regulatory pathways affecting cell metabolism and function. Wilcoxon matched-pairs signed rank test, Kruskal-Wallis test and Dunn multiple comparsion test were used for statistical analysis.Results:The proportion of Tpex in ATB group was 2.86%(1.74%), which was lower than 7.93%(6.16%) of Tex, and the difference was statistically significant ( Z=-3.91, P<0.001). The proportions of Tpex and Tex in LTBI group were 9.47%(6.26%) and 7.43%(5.48%), respectively, and the difference was not statistically significant ( Z=-0.93, P=0.345). The proportions of Tpex and Tex in healthy control group were 8.42%(2.69%) and 6.49%(5.14%), respectively, with no statistical significance ( Z=-1.36, P=0.170). There was statistical difference of the proportion of Tpex among the three groups ( H=21.93, P<0.001), and the proportion of Tpex in ATB group was lower than those in LTBI and heathy control groups, and the differences were both statistically significant ( Z=4.16, P<0.001 and Z=3.34, P=0.003, respectively), while the proportions of Tex in these three groups were not statistically different ( H=2.17, P=0.338). Compared with Tex, the gene expressions of memory markers, such as B-cell lymphoma 2 of Tpex were up-regulated, and the gene expressions of exhausted markers, such as lymphocyte activation gene 3 were down-regulated. In terms of cellular metabolism, the gene expressions of mitochondrial protein complex, mitochondrial matrix and oxidative phosphorylation of Tpex were up-regulated, and the gene expressions of glycolysis were down-regulated. The gene expressions of pyruvate metabolism in Tex were up-regulated, and the gene expressions of CD4 + T lymphocyte activation and differentiation and glycolytic process in Tpex were down-regulated. Conclusions:Tpex in ATB express more characteristics of memory cells and less features of exhausted markers compared with Tex, and the function of mitochondria of Tpex preserves well.

Uncovering the risk factors of pulmonary hypertension and its mechanisms is crucial for the prevention and treatment of the disease.In the current study,we showed that experimental periodontitis,which was established by ligation of molars followed by orally smearing subgingival plaques from patients with periodontitis,exacerbated hypoxia-induced pulmonary hypertension in mice.Mechanistically,periodontitis dysregulated the pulmonary microbiota by promoting ectopic colonization and enrichment of oral bacteria in the lungs,contributing to pulmonary infiltration of interferon gamma positive(IFNγ+)T cells and aggravating the progression of pulmonary hypertension.In addition,we identified Prevotella zoogleoformans as the critical periodontitis-associated bacterium driving the exacerbation of pulmonary hypertension by periodontitis,and the exacerbation was potently ameliorated by both cervical lymph node excision and IFNγ neutralizing antibodies.Our study suggests a proof of concept that the combined prevention and treatment of periodontitis and pulmonary hypertension are necessary.

Objective:To investigate the application of phase angle by bioelectrical impedance in the assessment of malnutrition and its correlation with nutrtition status as measured by several different screening tools in patients on maintenance hemodialysis (MHD).Methods:This was a cross-sectional study, including 151 patients on MHD. Bioelectrical impedance analysis was used to detect body composition in hemodialysis patients. Nutritional Risk Screening 2002 (NRS 2002) scores, body mass index (BMI) and the Global Leadership Initiative on Malnutrition (GLIM) criteria were used to investigate the prevalence of malnutrition in MHD patients. The correlation between phase angle and nutrition-related indicators such as visceral fat area, body weight, skeletal muscle, and serum albumin in MHD patients was analyzed, and the consistency between phase angle and the three screening tools was examined.Results:In a total of 151 patients on MHD, the malnutrition prevalence as measured by BMI, NRS 2002 score and GLIM criteria was 9.27%, 27.81% and 54.97%, respectively. Phase angle in MHD patients was positively correlated with BMI( P<0.01), negatively correlated with impaired nutrition score of NRS 2002( P<0.01), and also associated with nutrition screening results as measured by GLIM criteria( P<0.001). Further study showed that phase angle was positively correlated with body weight, skeletal muscle and serum albumin( P<0.01), but negatively with visceral fat area and extracellular water/total body water( P<0.01). Conclusions:Malnutrition is highly prevalent in MHD patients. Phase angle showed good consistency with BMI, NRS 2002 and GLIM criteria in terms of malnutrition screening, implying the potential application in the assessment of malnutrition in MHD patients. However, the clinical relevance still needs corroboration with future large-scale researches.