Parkinson's disease （PD） is a common neurodegenerative disorder characterized by motor impairments， with its pathological mechanisms involving multiple processes such as the degeneration of dopaminergic neurons and the abnormal aggregation of α-synuclein. Current Western medical treatments face challenges including diminished long-term efficacy and motor complications. In recent years， Traditional Chinese Medicine （TCM） has demonstrated advantages in the prevention and treatment of PD through its systematic regulatory capabilities， featuring multi-component， multi-target， and multi-pathway approaches.This article systematically reviews the roles of seven key signaling pathways-NF-κB， AMPK/mTOR， PI3K/Akt， MAPKs， Nrf2/ARE， Wnt/β-catenin， and BDNF/TrkB-in the pathological process of PD and the regulatory mechanisms of TCM. Research indicates that active ingredients of Chinese herbs and compound formulations can synergistically modulate these pathways， exerting comprehensive effects in inhibiting neuroinflammation， alleviating oxidative stress， promoting autophagy to clear abnormal proteins， and enhancing neurotrophic support. These signaling pathways form a complex regulatory network through crosstalk among key nodal molecules， constituting an intricate regulatory system in PD pathology. The multi-target intervention characteristics of TCM align well with this network-based regulatory requirement， achieving integrated anti-inflammatory， antioxidant， autophagy-regulating， and neurorestorative effects through synergistic multi-pathway modulation. This article systematically outlines the mechanisms of TCM in the coordinated regulation of multiple pathways， providing a theoretical basis for elucidating the pathological process of PD and the intervention mechanisms of TCM， while also offering new perspectives and directions for modern research on TCM in the prevention and treatment of PD.

Objective To explore the molecular mechanism by which SOS Ras/Rac guanine nucleotide exchange factor 1-intronic transcript 1(SOS1-IT1)affects enhancer of zeste homolog 2(EZH2)protein expression in endometrial cancer cells Ishikawa and RL95-2.Methods Lentiviral transfection of short hairpin RNA(shRNA)and overexpression plasmid were used in Ishikawa and RL95-2 cell lines to knock down and overexpress SOS1-IT1.The mechanism of EZH2 expression regulation was studied using Real-time PCR,Western blotting,and chromatin immunoprecipitation.Results The expression of SOS1-IT1 and EZH2 genes was positively correlated in endometrial cancer tissues.Knocking down SOS1-IT1 significantly reduces the expression of EZH2,inhibited the proliferation and migration of Ishikawa and RL95-2 cells,and could reduced the acetylation of histone H3 at position 27(H3K27)and the enrichment of CREB binding protein(CBP)in the EZH2 gene promoter region.Overexpression of SOS1-IT1 could increased the expression of EZH2 and enhance the acetylation of H3K27 and the enrichment of CBP.CBP could bind to SOS1-IT1 RNA,and this binding ability was weakened when CBP was knocked down.Conclusion SOS1-IT1 can promote the expression level of EZH2 in endometrial cancer cells Ishikawa and RL95-2 by regulating the acetylation modification level of the EZH2 gene promoter region,thereby affecting the proliferation and migration ability of endometrial cancer cells.

Objective:Primary pulmonary mucoepidermoid carcinoma(PMEC)is a rare malignant lung tumor that accounts for approxim-ately 0.1%-0.2%of all primary pulmonary neoplasms.Due to the non-specific clinical symptoms and epidemiological features,PMEC poses diagnostic challenges.Methods:Tissue blocks from 23 archived PMECs were collected from The First Affiliated Hospital of Soochow Uni-versity(November 2012 to December 2023).To establish definitive diagnoses,comprehensive histopathological evaluation,including histo-morphological analysis,immunohistochemistry(IHC),fluorescence in situ hybridization(FISH),and periodic acid-Schiff(PAS)staining were performed.Results:The tumors consisted of varying proportions of mucin-secreting cells(mucous cells),intermediate cells,and epidermoid cells.Immunophenotypically,CK7 was predominantly expressed in the mucous cells,whereas CK5/6,p40,and p63 were expressed in the epidermoid and intermediate cells.The Ki-67 proliferation index ranged from 5%to 60%.All tumors were negative for TTF-1 and Napsin A.Five of the tumors were positive for PD-L1(clone 22C3),with a tumor percentage score of 3%-20%.All 11 tumors tested for ALK(clone D5F3)were negative.IHC for c-Met was performed on two tumors and both were weakly positive(+).Mastermind-like transcriptional co-activator 2(MAML2)gene rearrangement was detected in 34.8%(8/23)of the tumors.Mucous cells were PAS positive.Kaplan-Meier surviv-al analysis revealed a significantly poorer prognosis for patients with lymph node metastasis,distant metastasis,advanced TNM stage(Ⅲ+Ⅳ),poor differentiation,or MAML2 gene rearrangement negativity.Univariate analysis identified poor histological differentiation,lymph node metastasis,distant metastasis,and advanced TNM stage as the major prognostic risk factors.Multivariate analysis confirmed poor differentiation and distant metastasis as independent risk factors for adverse outcomes.Conclusions:PMEC is an aggressive tumor with low incidence and non-specific clinical manifestations,leading to frequent misdiagnosis.Clinicians should maintain a high index of suspicion and ensure a thorough differential diagnosis.

Objective:To investigate the clinical efficacy of compound sabal berry tablets on overactive bladder symptoms in patients with benign prostatic hyperplasia after transurethral laser enucleation of the prostate.Methods:This study was a prospective study. Eighty patients with benign prostatic hyperplasia who underwent laser enucleation at Tongliao People's Hospital from January 2024 to December 2024 were included in this study. The patients were randomly divided into a study group and a control group using the random number table method, with 40 patients per group. The control group received 0.2 mg of tolterodine tartrate tablets twice a day after surgery. The study group was given compound sabal berry tablets (0.5 g orally three times a day) in addition to the treatment provided to the control group. Both groups of patients were treated for 4 weeks after surgery. The clinical efficacy of the two groups was compared, including the International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), Maximum Postoperative Urinary Flow Rate (Qmax), Post-Void Residual (PVR), and the incidence of postoperative bladder irritative symptoms.Results:The differences in the preoperative indicators, including IPSS, OABSS, Qmax, and PVR, between the two groups were not statistically significant (all P > 0.05). Preoperatively, in the control group, Qmax was (8.64 ± 2.83) mL/s, IPSS was (25.10 ± 4.37), OABSS was (10.52 ± 1.87), and PVR was (80.70 ± 6.34) mL; in the study group, the respective values were (9.12 ± 2.95) mL/s, (24.60 ± 4.53), (10.83 ± 1.73), and (80.10 ± 5.61) mL. Postoperatively, in the control group, Qmax was (20.30 ± 3.65) mL/s, IPSS was (8.50 ± 1.58), OABSS was (4.09 ± 0.52), and PVR was (9.70 ± 2.48) mL, while in the study group, the respective values were (21.40 ± 4.38) mL/s, (7.40 ± 1.76), (1.71 ± 0.36), and (9.00 ± 1.75) mL. Postoperatively, both groups showed a significant increase in Qmax, while IPSS, OABSS, and PVR all significantly decreased (all P < 0.05). Postoperatively, the IPSS and OABSS in the study group were significantly lower than those in the control group ( t = -3.28, -25.89, both P < 0.05). However, there were no statistically significant differences in Qmax and PVR between the two groups (both P > 0.05). The incidence of bladder irritative symptoms in the study group [12.50% (5/40)] was significantly lower than that in the control group [35.00% (14/40), χ2 = 8.64, P < 0.05]. Conclusions:Compound sabal berry tablets can reduce postoperative prostate symptoms and overactive bladder symptoms in patients undergoing transurethral laser enucleation of the prostate for benign prostatic hyperplasia, demonstrating a certain clinical efficacy.

Objective:To explore the influence of value orientation brief therapy (VBT) on anxiety and depression symptoms, social function, coping style and self-acceptance level of major depressive disorder adolescents with anxious distress.Methods:From June 2021 to June 2022, seventy adolescent major depressive disorder patients with anxious distress were included in the study, who were randomly divided into study group(35 people, 31 people completed)and control group (35 people, 30 people completed). The study group was given routine treatment combined with VBT, while the control group was given routine treatment only. Before and after treatment, Hamilton anxiety scale(HAMA), Hamilton depression scale (HAMD), social disability screening schedule (SDSS), coping style questionnaire(CSQ) and self-acceptance questionnaire (SAQ) were used to evaluate the two groups, and SPSS 26.0 software was used to statistically analyze the data of the two groups. Paired sample t-test was used for intra-group comparison, and independent sample t-test was used for inter-group comparison. Results:After 6 weeks of treatment, the scores of HAMA((6.03±3.58) vs (14.03±7.06), t=5.55, P<0.01), HAMD((8.77±5.52 ) vs (16.50±7.59), t=4.56, P<0.01)and SDSS((4.23±1.50) vs (6.63±0.96), t=7.43, P<0.01)in the study group were significantly lower than those in the control group, the differences were statistically significant. The scores of self-acceptance((19.23±1.33) vs (13.47±1.46), t=-16.12, P<0.01)and self-evaluation ((19.87±2.87) vs (12.77±1.68), t=-11.75, P<0.01) in the SAQ scale and the scores of problem-solving((8.71±2.30) vs (6.23±3.45), t=3.31, P<0.05) and rationalization ((6.20±3.11) vs (4.67±2.43), t=2.13, P<0.05) in the CSQ questionnaire were significantly higher than those in the control group, the differences were statistically significant. The total effective rate of the study group(90.3%(28/31) vs 66.7%(20/30), χ2=5.09, P<0.05) was significantly higher than that of the control group, the difference was statistically significant. Conclusion:The effect of routine treatment combined with VBT is better, which can effectively improve anxiety and depression symptoms, social function and coping style, and enhance self-acceptance and self-evaluation in adolescent major depressive disorder patients, which is worthy of clinical application.

Objective To investigate and compare the effects of electroacupuncture and dexamethasone on lung function and histomorphology and behavior in the offspring of perinatal nicotine exposure(PNE)rats.Methods Twenty-four pregnant Sprague-Dawley rats were randomly divided into control,model,electroacupuncture shallow needling,and dexamethasone groups using the random number table method(n=6 rats per group).A pulmonary dysplasia model in offspring rats with PNE was prepared by cervicodorsal subcutaneous injection with nicotine,and successful establishment of the model was confirmed by demonstrating statistically significant differences in growth parameters,lung function,and lung morphology compared to the control group.From the sixth day of maternal conception,the control group received cervicodorsal subcutaneous injection with 0.9%sodium chloride solution(1 mg/kg once per day),and the remaining groups were similarly injected with nicotine(1 mg/kg once per day).Concurrent with the nicotine injections,the electroacupuncture shallow needling group received electroacupuncture interventions at the"Zusanli"(ST 36)acupoint on both sides once a day for 20 min.In contrast,the offspring rats in the dexamethasone group received intraperitoneal dexamethasone injections from postnatal day 8(1.5 mg/kg once per day for 3 days),with a later dose of 0.75 mg/kg once per day for 4 days.Following successful model establishment,four offspring per rat were retained in each group using the random number table method.Until the 21st day after the birth of the offspring,using the random number table method,one offspring randomly selected from the four retained offspring per rat in each group was assigned to growth parameter assessment including body weight,lung weight,and lung index;simultaneously,one offspring was randomly selected for pulmonary function which was detected by a small animal pulmonary function machine,with the parameters of forced vital capacity(FVC),functional residual capacity(FRC),dynamic lung compliance(Cdyn),peak expiratory flow(PEF),peak inspiratory flow(PIF),and airway resistance(RL);concurrently,one offspring was randomly selected for hematoxylin and eosin staining to observe the histomorphology of the lung tissue,alveolar numbers,and mean alveolar septal thickness;additionally,one offspring was randomly selected for Morris water maze testing to evaluate the effects of the two intervention methods on learning and memory capabilities in offspring rats with PNE.Results Compared with the control group,the body weight,lung weight,lung index,FVC,PEF,FRC,Cdyn,alveolar number,platform crossing times,target quadrant time percentage,and target quadrant path percentage in the Morris water maze experiment were significantly decreased in the offspring rats of the model group(P<0.01).In contrast,PIF,RL,average thickness of alveolar septa,and latency of the Morris water maze experiment were significantly increased in the offspring rats of the model group(P<0.01).Compared with the model group,both electroacupuncture shallow needling group and dexamethasone group exhibited significant increases in body weight,lung weight,lung index,FVC,PEF,FRC,Cdyn,and alveolar numbers(P<0.05,P<0.01),along with significant decreases in PIF,RL values,and mean alveolar septal thickness(P<0.01).However,in the Morris water maze experiment,compared with the model group,the electroacupuncture shallow needling group demonstrated significantly more platform crossing times and a higher target quadrant time percentage and target quadrant path percentage(P<0.01),coupled with reduced latency period(P<0.01),whereas the dexamethasone group showed no significant differences compared to the model group.Compared to the electroacupuncture shallow needling group,the dexamethasone group showed significantly less platform crossing times and a lower target quadrant time percentage and target quadrant path percentage,coupled with increased latency period(P<0.01).Conclusion Both electroacupuncture and dexamethasone demonstrated protective effects on lung development in PNE offspring rats by ameliorating lung histomorphology and pulmonary function.However,offspring receiving late,small-dose,short-course dexamethasone exhibited inferior learning and memory capabilities,whereas the electroacupuncture group showed significantly superior cognitive performance compared to the dexamethasone group.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.

Insulin is an important protein hormone that participates in multiple metabolic pathways.Biosynthetic insulin has been widely used in the treatment of type 1 and type 2 diabetes.Currently,the number of reported cases of insulin overdose both at home and abroad is gradually increasing,and insulin homicide is no longer a means of"committing murder without leaving a trace".At present,there are no systematic protocols for the identification of insulin overdose in the field of forensic medi-cine in China.This article introduces the causes,toxicological characteristics,forensic examination,labo-ratory testing methods and indicator reference of insulin overdose.Based on the identification practice and research results and referring to relevant studies on insulin overdose at home and abroad,this pa-per aims to provide recommendations and references for the formulation of forensic identification guide-lines for insulin overdose cases.

OBJECTIVE: Peritoneal fibrosis (PF) is an adverse event that occurs during long-term peritoneal dialysis, significantly impairing treatment efficiency and adversely affecting patient outcomes. Astragaloside IV (AS-IV), a principal active component derived from Astragalus membranaceus (Fisch.) Bunge, has exhibited anti-inflammatory and antifibrotic effects in various settings. This study aims to investigate the potential therapeutic efficacy and mechanism of AS-IV in the treatment of PF. METHODS: The PF mouse model was established by intraperitoneal injection of 4.25% peritoneal dialysis fluid (100 mL/kg). The epithelial-mesenchymal transition (EMT) of HMrSV5 cells was induced by the addition of 10 ng/mL transforming growth factor β (TGF-β). The differentially expressed genes in HMrSV5 cells treated with AS-IV were screened using transcriptome sequencing analysis. The potential targets of AS-IV were screened using network pharmacology and analyzed using molecular docking and molecular dynamics simulations. RESULTS: Administration of AS-IV at doses of 20, 40, or 80 mg/kg effectively mitigated the increase in peritoneal thickness and the development of fibrosis in mice with PF. The expression of the fibrosis marker α-smooth muscle actin in the peritoneum was significantly decreased in AS-IV-treated mice. The treatment of AS-IV (10, 20, and 40 μmol/L) significantly delayed the EMT of HMrSV5 cells induced by TGF-β, as demonstrated by the decreased number of 5-ethynyl-2'-deoxyuridine-positive cells, reduced migrated area, and decreased expression of fibrosis markers. A total of 460 differentially expressed genes were detected in AS-IV-treated HMrSV5 cells through transcriptome sequencing, with notable enrichment in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-AKT serine/threonine kinase 1 (AKT) signaling pathway. The reduced levels of phosphorylated PI3K (p-PI3K) and p-AKT were detected in HMrSV5 cells with AS-IV treatment. Epidermal growth factor receptor (EGFR) was predicted as a direct target of AS-IV, exhibiting strong hydrogen bond interactions. The activation of the PI3K-AKT pathway by the compound 740Y-P, and the activation of the EGFR pathway by NSC 228155 each partially counteracted the inhibitory effect of AS-IV on the EMT of HMrSV5 cells. CONCLUSION AS-IV delayed the EMT process in peritoneal mesothelial cells and slowed the progression of PF, potentially serving as a therapeutic agent for the early prevention and treatment of PF. Please cite this article as: Huang Y, Chu CL, Qiu WH, Chen JY, Cao LX, Ji SY, Zhu B, Wang GK, Shen QQ. Astragaloside IV delayed the epithelial-mesenchymal transition in peritoneal fibrosis by inhibiting the activation of EGFR and PI3K-AKT pathways. J Integr Med. 2025; 23(6):694-705.
Epithelial-Mesenchymal Transition/drug effects* ; Animals ; Saponins/pharmacology* ; Triterpenes/pharmacology* ; Mice ; Peritoneal Fibrosis/pathology* ; Proto-Oncogene Proteins c-akt/metabolism* ; ErbB Receptors/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Signal Transduction/drug effects* ; Male ; Humans ; Molecular Docking Simulation ; Cell Line ; Mice, Inbred C57BL