BACKGROUND:Studies have confirmed that Pterocarya hupehensis skan total flavonoids(PHSTF)can improve the level of collagen-induced arthritis in rats,but there is still a lack of research on the regulation of Wnt/β-catenin signaling pathway in fibroblast-like synoviocytes and its effect on related cell functions.OBJECTIVE:To investigate the effect and mechanism of PHSTF on lipopolysaccharide-induced proliferation,migration and apoptosis of fibroblast-like synoviocytes based on the Wnt/β-catenin signaling pathwayMETHODS:Fibroblast-like synoviocytes were divided into control group,lipopolysaccharide group,lipopolysaccharide+low-,medium-,and high-dose PHSTF groups(10,20,and 40 μg/mL),lipopolysaccharide+Wnt pathway inhibitor DKK1 group,and lipopolysaccharide+Wnt pathway inhibitor DKK1+high-dose PHSTF group(40 μg/mL).The cell counting kit-8 method was used to detect the effect of PHSTF on the viability of fibroblast-like synoviocytes,and the final drug concentration and time were screened.Flow cytometry was used to detect the apoptosis of fibroblast-like synoviocytes.Cell scratch assay,EDU staining and cell cloning assay were used to detect the migration and proliferation of fibroblast-like synoviocytes.Western blot assay was used to detect the protein expression levels of Wnt3a,β-catenin,tumorigenic genes,matrix metalloproteinase 2,matrix metalloproteinase 9,Bax and Bcl-2 in fibroblast-like synoviocytes.RESULTS AND CONCLUSION:(1)Compared with the control group,the cell viability decreased significantly when the concentration of PHSTF was＞40 μg/mL(P＜0.01).Therefore,the drug concentration of≤40 μg/mL was selected for subsequent experiments.(2)Compared with the lipopolysaccharide group,the wound healing rate,cell clone formation rate and the number of EDU-positive cells in the low-,medium-and high-dose PHSTF groups were significantly reduced,while the apoptosis rate was significantly increased(P＜0.05-0.01).(3)Western blot results showed that compared with the lipopolysaccharide group,low-,medium-and high-dose PHSTF significantly inhibited cellular Wnt3a,β-catenin,cellular tumorigenic genes,matrix metalloproteinase 2,matrix metalloproteinase 9,and Bcl-2 protein expression,and promoted the expression of Bax protein(P＜0.01).(4)Compared with the DKK1 group,the combination of DKK1 and high-dose PHSTF significantly inhibited the protein expression of Wnt3a,β-catenin,matrix metalloproteinase 2,matrix metalloproteinase 9 and Bcl-2 protein expression and promoted the protein expression of Bax(P＜0.01).To conclude,PHSTF may inhibit the proliferation and migration of fibroblast-like synoviocytes and promote apoptosis by inhibiting the Wnt/β-catenin signaling pathway.

BACKGROUND:Studies have confirmed that Pterocarya hupehensis skan total flavonoids(PHSTF)can improve the level of collagen-induced arthritis in rats,but there is still a lack of research on the regulation of Wnt/β-catenin signaling pathway in fibroblast-like synoviocytes and its effect on related cell functions.OBJECTIVE:To investigate the effect and mechanism of PHSTF on lipopolysaccharide-induced proliferation,migration and apoptosis of fibroblast-like synoviocytes based on the Wnt/β-catenin signaling pathwayMETHODS:Fibroblast-like synoviocytes were divided into control group,lipopolysaccharide group,lipopolysaccharide+low-,medium-,and high-dose PHSTF groups(10,20,and 40 μg/mL),lipopolysaccharide+Wnt pathway inhibitor DKK1 group,and lipopolysaccharide+Wnt pathway inhibitor DKK1+high-dose PHSTF group(40 μg/mL).The cell counting kit-8 method was used to detect the effect of PHSTF on the viability of fibroblast-like synoviocytes,and the final drug concentration and time were screened.Flow cytometry was used to detect the apoptosis of fibroblast-like synoviocytes.Cell scratch assay,EDU staining and cell cloning assay were used to detect the migration and proliferation of fibroblast-like synoviocytes.Western blot assay was used to detect the protein expression levels of Wnt3a,β-catenin,tumorigenic genes,matrix metalloproteinase 2,matrix metalloproteinase 9,Bax and Bcl-2 in fibroblast-like synoviocytes.RESULTS AND CONCLUSION:(1)Compared with the control group,the cell viability decreased significantly when the concentration of PHSTF was＞40 μg/mL(P＜0.01).Therefore,the drug concentration of≤40 μg/mL was selected for subsequent experiments.(2)Compared with the lipopolysaccharide group,the wound healing rate,cell clone formation rate and the number of EDU-positive cells in the low-,medium-and high-dose PHSTF groups were significantly reduced,while the apoptosis rate was significantly increased(P＜0.05-0.01).(3)Western blot results showed that compared with the lipopolysaccharide group,low-,medium-and high-dose PHSTF significantly inhibited cellular Wnt3a,β-catenin,cellular tumorigenic genes,matrix metalloproteinase 2,matrix metalloproteinase 9,and Bcl-2 protein expression,and promoted the expression of Bax protein(P＜0.01).(4)Compared with the DKK1 group,the combination of DKK1 and high-dose PHSTF significantly inhibited the protein expression of Wnt3a,β-catenin,matrix metalloproteinase 2,matrix metalloproteinase 9 and Bcl-2 protein expression and promoted the protein expression of Bax(P＜0.01).To conclude,PHSTF may inhibit the proliferation and migration of fibroblast-like synoviocytes and promote apoptosis by inhibiting the Wnt/β-catenin signaling pathway.

Male infertility has become a global concern, accounting for 20-70% of infertility. Dysfunctional spermatogenesis is the most common cause of male infertility; thus, treating abnormal spermatogenesis may improve male infertility and has attracted the attention of the medical community. Mitochondria are essential organelles that maintain cell homeostasis and normal physiological functions in various ways, such as mitochondrial oxidative phosphorylation (OXPHOS). Mitochondrial OXPHOS transmits electrons through the respiratory chain, synthesizes adenosine triphosphate (ATP), and produces reactive oxygen species (ROS). These mechanisms are vital for spermatogenesis, especially to maintain the normal function of testicular Sertoli cells and germ cells. The disruption of mitochondrial OXPHOS caused by external factors can result in inadequate cellular energy supply, oxidative stress, apoptosis, or ferroptosis, all inhibiting spermatogenesis and damaging the male reproductive system, leading to male infertility. This article summarizes the latest pathological mechanism of mitochondrial OXPHOS disorder in testicular Sertoli cells and germ cells, which disrupts spermatogenesis and results in male infertility. In addition, we also briefly outline the current treatment of spermatogenic malfunction caused by mitochondrial OXPHOS disorders. However, relevant treatments have not been fully elucidated. Therefore, targeting mitochondrial OXPHOS disorders in Sertoli cells and germ cells is a research direction worthy of attention. We believe this review will provide new and more accurate ideas for treating male infertility.
Male ; Humans ; Infertility, Male/metabolism* ; Oxidative Phosphorylation ; Mitochondria/metabolism* ; Spermatogenesis/physiology* ; Sertoli Cells/metabolism* ; Oxidative Stress/physiology* ; Animals ; Reactive Oxygen Species/metabolism*

Chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH) are both chronic progressive respiratory diseases that cannot be completely cured. COPD is characterized by irreversible airflow limitation, chronic airway inflammation, and gradual decline in lung function, whereas PH is characterized by pulmonary vasoconstriction, remodeling, and infiltration of inflammatory cells. These diseases have similar pathological features, such as vascular hyperplasia, arteriolar contraction, and inflammatory infiltration. Despite these well-documented observations, the exact mechanisms underlying the occurrence and development of COPD and PH remain unclear. Evidence that mitochondrial dynamics imbalance is one major factor in the development of COPD and PH. Mitochondrial dynamics is precisely regulated by mitochondrial fusion proteins and fission proteins. When mitochondrial dynamics equilibrium is disrupted, it causes mitochondrial and even cell morphological dysfunction. Mitochondrial dynamics participates in various pathological processes for heart and lung disease. Mitochondrial dynamics may be different in the early and late stages of COPD and PH. In the early stages of the disease, mitochondrial fusion increases, inhibiting fission, and thereby compensatorily increasing adenosine triphosphate (ATP) production. With the development of the disease, mitochondria decompensation causes excessive fission. Mitochondrial dynamics is involved in the development of COPD and PH in a spatiotemporal manner. Based on this understanding, treatment strategies for mitochondrial dynamics abnormalities may be different at different stages of COPD and PH disease. This article will provide new ideas for the potential treatment of related diseases.
Humans ; Mitochondrial Dynamics/physiology* ; Pulmonary Disease, Chronic Obstructive/metabolism* ; Hypertension, Pulmonary/metabolism* ; Mitochondria/metabolism* ; Animals

Objective To investigate the lipid-lowering efficacy and safety of Xuezhikang combined with PCSK9 inhibitor in patients with coronary heart disease.Methods A total of 102 patients with coronary heart disease hospitalized in Jiangxi Provincial People's Hospital from June 2023 to November 2024 were enrolled in this study and randomly divided into a control group(50 cases)and an experimental group(52 cases).The control group received basic medication for secondary prevention of coronary heart disease,while the experi-mental group received Xuezhikang combined with PCSK9 inhibitor in addition to the basic medication.After 6 months of treatment,blood lipid indicators,liver function indicators,kidney function indicators,incidence of major adverse cardiovascular events(MACE),and incidence of adverse drug reactions were observed.Results After treatment,LDL-C,TC,AST,and ALT levels decreased in both groups compared with before treatment.The experimental group showed significantly lower levels of these indicators than the control group,with statistically significant differences(P<0.05).Both groups had one case of adverse drug reaction each,showing no statistically significant difference(P>0.05).The MACE incidence was higher in the control group than in the experimental group(18.0%vs.3.8%,P<0.05).The lipid goal achievement rate was low-er in the control group than in the experimental group(44.0%vs.73.1%,P<0.05).Conclusion The com-bination of Xuezhikang and PCSK9 inhibitors demonstrates definite clinical efficacy in coronary heart disease patients,reduces MACE risk,and improves lipid goal achievement rates.

Objective To conduct bibliometric visualization analyses of the literature domestic and overseas on active surveillance of post-marketing safety of drugs,aiming to display the current status and trend of hotspots in this field and to provide references for future research and the improvement of the Chinese management system of active surveillance.Methods The English and Chinese literature on active surveillance of post-marketing safety of drugs were searched in Web of Science and CNKI respectively and imported into CiteSpace 6.3.R2 software for the analysis of the number of publications,authors,institutions,and national cooperative networks,and the analysis of keyword co-occurrence,clustering and emergence.Results 415 Chinese and 676 English literature were included,with an overall increasing trend in annual publication volume.The author collaboration network of Chinese literature was smaller than that of English literature,and the partnership network was sparse,with no strong centralized institution.Domestic drug regulatory agencies played an important role in the field,while drug companies'monitoring research on their own products was still relatively scarce.The research topic covered active surveillance systems,technical method research,and drug safety active surveillance practice research for specific drugs and diseases.Conclusion Countries worldwide have widely considered active surveillance of post-marketing drug safety.The heat of research activities in China has shown a significant growth trend.However,there is still a significant gap compared with the international frontiers.Further cooperation needs to be strengthened to promote the improvement of the active surveillance management system in China.

Objective:To explore the medication law of TCM compounds used in the treatment of non-small cell lung cancer (NSCLC).Methods:Clinical literature about TCM compounds in the treatment of NSCLC was retrieved from CNKI, Wanfang Data, PubMed and Web of Science core collection database from January 1st, 2003 to May 1st, 2023. The Python and the ancient and modern medical record cloud platform V2.3.7 were used to analyses frequency statistics and properties, and clustering analysis, factor analysis and association rule analysis were performed.Results:A total of 866 articles were included, with 660 effective TCM compounds, 647 kinds of Chinese materia medica. There were 36 kinds of high-frequency Chinese materia medica, such as Astragali Radix, Atractylodis Macrocephalae Rhizoma and Poria; the efficacy categories of Chinese materia medica mainly included tonics and phlegm resolving cough relieving and asthma relieving drugs. Cluster analysis obtained 4 clusters, factor analysis extracted 11 common factors, and association rule analysis obtained 37 highly supported combinations of Chinese materia medica. The most reliable triple drug combination among them was Astragali Radix-Atractylodis Macrocephalae Rhizoma-Hedyotis diffusa willd, and the double drug combination was Astragali Radix-Ligustri Lucidi Fructus.Conclusion:TCM for the treatment of NSCLC mainly focuses on strengthening the healthy qi, clearing heat, resolving phlegm and detoxifying toxins, supplemented by tonifying qi and activating blood circulation, dispelling dampness and resolving phlegm.

Objective To investigate the effect of semaglutide on the prognosis in patients with unstable angina complicated with diabetes after percutaneous coronary intervention.Methods A total of 178 patients with unstable angina complicated with diabetes diagnosed in Zhengzhou Cardiovascular Hospital from September 1,2022 to March 31,2023 were included.The patients were divided into a study group(43 patients)and a control group(135 patients)according to whether they received semiglutide or not.Changes in HbA1c,fasting blood glucose,body weight,blood pressure and blood lipid were observed before and after treatment.Baseline data and differences in postoperative adverse cardiovascular events including cardiovascular death,all-cause death,acute myocardial infarction,acute ischemic stroke,re-hospitalization due to unstable angina,and coronary revasculariza-tion were compared between the two groups.Results After 12 weeks of treatment,fasting blood-glucose levels in the study group and the control group were(6.0±0.9),(8.5±1.3)mmol/L,HbA1c levels were(6.5±0.7)%,(7.9±0.5)%,BMI was(22.8±3.0),(25.0±2.4)kg/m2,systolic blood pressure was(135.3±9.7),(141.5±8.3)mmHg,respectively,with significant differences(P＜0.05 for all comparisons).Diastolic blood pressure showed a trend of improvement(84.7±7.7),(86.6±7.7)mmHg,but there was no statistical difference.Conclu-sions For patients with unstable angina complicated with diabetes after percutaneous coronary intervention,the application of semaglutide can effectively control blood glucose,body weight,systolic blood pressure,and reduce the risk of cardiovascular events.

Objective To investigate the effect of semaglutide on the prognosis in patients with unstable angina complicated with diabetes after percutaneous coronary intervention.Methods A total of 178 patients with unstable angina complicated with diabetes diagnosed in Zhengzhou Cardiovascular Hospital from September 1,2022 to March 31,2023 were included.The patients were divided into a study group(43 patients)and a control group(135 patients)according to whether they received semiglutide or not.Changes in HbA1c,fasting blood glucose,body weight,blood pressure and blood lipid were observed before and after treatment.Baseline data and differences in postoperative adverse cardiovascular events including cardiovascular death,all-cause death,acute myocardial infarction,acute ischemic stroke,re-hospitalization due to unstable angina,and coronary revasculariza-tion were compared between the two groups.Results After 12 weeks of treatment,fasting blood-glucose levels in the study group and the control group were(6.0±0.9),(8.5±1.3)mmol/L,HbA1c levels were(6.5±0.7)%,(7.9±0.5)%,BMI was(22.8±3.0),(25.0±2.4)kg/m2,systolic blood pressure was(135.3±9.7),(141.5±8.3)mmHg,respectively,with significant differences(P＜0.05 for all comparisons).Diastolic blood pressure showed a trend of improvement(84.7±7.7),(86.6±7.7)mmHg,but there was no statistical difference.Conclu-sions For patients with unstable angina complicated with diabetes after percutaneous coronary intervention,the application of semaglutide can effectively control blood glucose,body weight,systolic blood pressure,and reduce the risk of cardiovascular events.

Objective:To investigate the clinical efficacy of radical resection of rectal cancer with different surgical approaches and influencing factors of postoperative complications.Methods:The retrospective study was conducted. The clinicopathological data of 3 418 patients who underwent radical resection of rectal cancer in the Second Affiliated Hospital of Harbin Medical University from July 2011 to September 2020 were collected. There were 2 060 males and 1 358 females, aged (61±11)years. Patients meeting the requirements of radical resection and surgical indications underwent surgeries choosing from open radical colorectal cancer surgery, laparoscopic radical colorectal cancer surgery, and natural orifice specimen extraction surgery (NOSES). Observation indicators: (1) intraoperative and postoperative conditions of patients undergoing different surgical approaches; (2) comparison of preoperative clinical characteristics in patients undergoing different surgical approaches; (3) comparison of postoperative histopathological characteristics in patients undergoing different surgical approaches; (4) postoperative complications of patients undergoing different surgical approaches; (5) analysis of influencing factors of postoperative complications. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M(range), and comparisons between groups was analyzed using the Kruskal-Wallis rank test. Comparison of ordinal data was analyzed using the non-parameter rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Multivariate analysis was conducted using the Logistic regression model. Results:(1) Intraoperative and postoperative conditions of patients undergoing different surgical approaches. Of the 3 418 patients, 1 978 cases underwent open radical colorectal cancer sur-gery, 1 028 cases underwent laparoscopic radical colorectal cancer surgery and 412 cases underwent NOSES, respectively. The operation time, volume of intraoperative blood loss, cases with permanent stoma, preventive stoma or without fistula, time to postoperative first flatus, time to postoperative liquid food intake, cases transferred to intensive care unit after surgery, duration of postoperative hospital stay were 145(range, 55?460)minutes, 100(range, 30?1 000)mL, 435, 88, 1 455, 72(range, 10?220)hours, 96(range, 16?296)hours, 158, 10(range, 6?60)days, respectively, in patients undergoing open radical colorectal cancer surgery. The above indicators were 175(range, 80?450)minutes, 50(range, 10?800)mL, 172, 112, 744, 48(range, 14?120)hours, 72(range, 38?140)hours, 17, 9(range, 4?40)days, respectively, in patients undergoing laparoscopic radical colorectal cancer surgery and 180(range, 80?400)minutes, 30(range, 5?500)mL, 0, 45, 367, 48 (range, 14?144)hours, 72(range, 15?148)hours, 1, 6(range, 3?30)days, respectively, in patients undergoing NOSES. There were significant differences in the above indicators among the patients undergoing different surgical approaches ( H=291.38, 518.56, χ2=153.82, H=408.86, 282.97, χ2=78.66, H=332.30, P<0.05). (2) Com-parison of preoperative clinical characteristics in patients undergoing different surgical approaches. The gender, age, body mass index, cases with diabetes, cases with hypertension, cases with coronary heart disease, cases with anemia, cases with hypoproteinemia, cases with intestinal obstruction, tumor location, preoperative carcinoembryonic antigen, preoperative CA19-9 showed significant differences among patients undergoing open radical colorectal cancer surgery, laparoscopic radical colorectal cancer surgery and NOSES ( P<0.05). (3) Comparison of postoperative histopathological characteris-tics in patients undergoing different surgical approaches. Tumor histological type, tumor differentiation degree, tumor diameter, number of lymph node detected, nerve invasion, vascular invasion, lymph node invasion, tumor T staging, tumor N staging, tumor M staging, tumor TNM staging showed significant differences among patients undergoing open radical colorectal cancer surgery, laparos-copic radical colorectal cancer surgery and NOSES ( P<0.05). (4) Postoperative complications of patients undergoing different surgical approaches. Cases with postoperative complications as anastomotic leakage, abdominal infection, intestinal obstruction, anastomotic bleeding, incision complications, pulmonary infection, other complications were 52, 21, 309, 8, 130, 51, 59, respectively, in patients undergoing open radical colorectal cancer surgery. The above indicators were 33, 17, 75, 3, 45, 58, 9, respectively, in patients undergoing laparoscopic radical colorectal cancer surgery and 13, 4, 8, 0, 11, 10, 15, respectively, in patients undergoing NOSES. There were significant differences in the intes-tinal obstruction, incision complications, pulmonary infection, other complications among patients undergoing different surgical approaches ( χ2=122.56, 13.33, 20.44, 15.59, P<0.05) and there was no significant difference in the anastomotic leakage, abdominal infection, anastomotic bleeding among patients undergoing different surgical approaches ( χ2=0.96, 2.21, 3.08, P>0.05). (5) Analysis of influencing factors of postoperative complications. ① Analysis of influencing factors of intestinal obstruction in patients with radical resection of rectal cancer. Age as 20?39 years and 40?59 years, surgical approach as laparoscopic radical colorectal cancer surgery and NOSES were independent protective factors of intestinal obstruction in patients with radical resection of rectal cancer ( odds ratio=0.46, 0.59, 0.43, 0.13, 95% confidence interval as 0.21?1.00, 0.36?0.96, 0.33?0.56, 0.06?0.27, P<0.05). ② Analysis of influencing factors of incision complications in patients with radical resection of rectal cancer. Body mass index as 24.0?26.9 kg/m 2, surgical approach as laparoscopic radical colorectal cancer surgery and NOSES were independent protective factors of incision complications in patients with radical resection of rectal cancer ( odds ratio=0.24, 0.63, 0.46, 95% confidence interval as 0.11?0.51, 0.44?0.89, 0.24?0.87, P<0.05). ③ Analysis of influencing factors of pulmonary infection in patients with radical resection of rectal cancer. The surgical approach as laparoscopic radical colorectal cancer surgery was an independent risk factor of pulmonary infection in patients with radical resection of rectal cancer ( odds ratio=2.15, 95% confidence interval as 1.46?3.18, P<0.05), and tumor TNM staging as 0?Ⅰ stage was an independent protective factor ( odds ratio=0.10, 95% confidence interval as 0.01?0.88, P<0.05). ④ Analysis of influencing factors of other complica-tions in patients with radical resection of rectal cancer. Age as 20?39 years, 40?59 years, 60?79 years, body mass index as <18.5 kg/m 2, 18.5?23.9 kg/m 2, 24.0?26.9 kg/m 2, 27.0?29.9 kg/m 2, surgical approach as laparoscopic radical colorectal cancer surgery were independent protective factors of other complications in patients with radical resection of rectal cancer ( odds ratio=0.10, 0.29, 0.37, 0.08, 0.22, 0.35, 0.32, 0.29, 95% confidence interval as 0.01?0.81, 0.13?0.64, 0.17?0.78, 0.02?0.40, 0.09?0.52, 0.15?0.83, 0.12?0.89, 0.14?0.59, P<0.05). Conclusions:Compared to laparoscopic radical colorectal cancer surgery and NOSES, open radical colorectal cancer surgery has wide indication and short operation time, but less perioperative treatment effect. Laparoscopic radical colorectal cancer surgery and NOSES can achieve better surgical result and less postoperative complication when patients meeting surgical indications.