1.Lysosomes as Regulators of Cancer Stemness and Drug Resistance
Fa-Xiao ZHOU ; Di-Ping YU ; Si-Qi TAN ; Hong-Yu DUAN ; Xiao-Ming WU
Progress in Biochemistry and Biophysics 2026;53(4):951-967
Cancer stem cells (CSCs) represent a distinct subpopulation of cells characterized by self-renewal capacity, differentiation potential, and critical roles in driving tumor progression, therapeutic resistance, recurrence, and maintenance of the tumor microenvironment. Targeting CSCs has emerged as a pivotal direction in cancer research, offering novel strategies to overcome drug resistance and prevent metastasis and relapse. Lysosomes, traditionally recognized as central organelles for intracellular degradation and recycling, are indispensable for cellular homeostasis. Dysregulation of lysosomal function is intimately linked to various diseases, including cancer. In tumors, aberrant lysosomal activity can promote malignant progression through mechanisms such as altering metabolic pathways, enhancing lysosomal exocytosis, modulating drug resistance, and interfering with autophagy-lysosomal pathways. Recent studies have underscored the involvement of lysosomes in regulating CSC properties. This review synthesizes findings on lysosomal regulation of CSCs through the following aspects. (1) Lysosomes exert complex and critical bidirectional control over CSC stemness maintenance through three degradation pathways that are dependent on their degradative function. (i) The lysophagy pathway. This pathway exhibits dual roles. Activation can sustain CSC functions; for instance, in glioblastoma, hypoxia upregulates Gal-8 via the STAT3/HIF1α signaling axis to induce autophagy, supporting stem cell survival. In head and neck squamous cell carcinoma, degradation of GSK3β activates the Wnt pathway, enhancing stemness. Conversely, this pathway can suppress stemness by degrading stemness-related proteins such as BMI-1 and OCT4A, thereby impairing CSC self-renewal capacity. (ii) Mitophagy pathway. In non-small cell lung cancer stem cells, mitophagy-related mechanisms, such as the accumulation of mitochondrial DNA (mtDNA) activating the TLR9-Notch1-AMPK signaling axis, have been shown to promote CSC proliferation. (iii) Autophagosome-dependent lysosomal degradation pathway. This pathway directly regulates stemness-related proteins in a bidirectional manner. Enhanced degradative function can promote CSC properties, exemplified by the degradation of NUMB to activate Notch signaling. Conversely, attenuated degradative function can also enhance stemness by stabilizing oncoproteins (e.g., protecting Frizzled-1 from degradation to sustain Wnt signaling) or preventing the degradation of tumor suppressors (e.g., inhibiting Notch degradation). (2) Constituent proteins of lysosomes, including membrane proteins and luminal acid hydrolases, participate in regulating CSC stemness. Regarding membrane proteins, LAMP2A facilitates chaperone-mediated autophagy to maintain stemness in glioblastoma and ovarian cancer. V-ATPase, by maintaining an acidic luminal environment, promotes proliferation and drug resistance in glioma stem cells. Among hydrolases, cathepsins B and L are highly expressed in pancreatic and ovarian cancers and correlate with poor prognosis. Furthermore, targeting lysosomes to induce lysosomal membrane permeabilization (LMP) triggers lysosome-mediated cell death, presenting a potential therapeutic strategy for eradicating CSCs.(3) The acidic luminal environment, single-membrane structure, and the presence of transmembrane transporters (e.g., ABCA3) enable lysosomes to passively trap or actively uptake and sequester chemotherapeutic drugs. Subsequent drug extrusion via exocytosis confers drug resistance. In CSCs, this lysosome-mediated drug sequestration, often cooperating with autophagy, establishes multimodal drug resistance. Therefore, targeting lysosomal function represents a potential strategy to overcome therapy resistance. The central role of lysosomes in regulating CSC stemness and resistance positions them as highly promising therapeutic targets. Strategies aimed at disrupting lysosomal function to selectively eliminate CSCs include: inhibiting the lysosome-autophagy system using agents like IITZ or lovastatin; inducing lysosomal membrane permeabilization (LMP) with compounds such as hexamethylene amiloride to compromise membrane stability; and disrupting the acidic luminal environment using drugs like siramesine or the K/H transport compound 2. In conclusion, lysosomes critically regulate CSC stemness maintenance and drug resistance through degradative pathways, membrane protein functions, luminal hydrolase activities, and drug sequestration mechanisms. This redefines the lysosome from a traditional “waste disposal unit” to a “signal integration center” in CSCs. The duality and context-dependency of lysosomal function in CSCs offer novel insights into the heterogeneity observed across different tumors. Targeting lysosomal vulnerabilities—such as inducing LMP, disrupting acidity, or blocking autophagic flux—provides a strategy to bypass canonical CSC resistance mechanisms and directly trigger cell death. This establishes the lysosome as a key target to overcome CSC-mediated therapy resistance, paving the way for developing diverse candidate drugs and innovative combination therapies in oncology.
2.Herbal Textual Research on Bambusae Succus in Famous Classical Formulas
Yu SHI ; Feng ZHOU ; Yihan WANG ; Yanmeng LIU ; Ming YANG ; Zhiping CHEN ; Jiangshan ZHANG ; Conglong XU ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(9):231-239
This article systematically reviews and examines the historical evolution of Bambusae Succus as a medicinal material, covering aspects such as nomenclature, origin, geographical distribution, harvesting and processing methods, quality assessment, therapeutic effects and indications, by consulting ancient herbal texts, medical compendia, and modern literature. The aim is to provide a reference for the development and utilization of famous classical formulas containing this herb. Research indicated that Bambusae Succus was first documented in the Shennong Bencaojing during the Han dynasty, with Zhuli being the standard name used throughout history, alongside aliases like Zhuzhi, Zhuyou and Huoquan. Historically, the primary source of Bambusae Succus has been Phyllostachys nigra var. henonis(Danzhu), although other species such as Pleioblastus amarus and Bambusa emeiensis have also been used medicinally. Ancient records predominantly noted its origin in Yizhou(present-day Chengdu and surrounding areas in Sichuan) and the Wuling region(between present-day Hunan, Guangdong, Guangxi and Jiangxi provinces), while contemporary sources are mainly from regions south of the Yangtze River and southwestern China. Traditionally, Bambusae Succus was harvested from bamboo that had grown for exactly one year, today, it can be collected year-round without strict age requirements. Ancient preparation methods included direct fire roasting or dry distillation, whereas modern industrial production employs dry distillation, reflux extraction, and percolation. In terms of quality evaluation, ancient texts considered a sweet taste to be superior, while today, clarity and transparency are prioritized. Historically, Bambusae Succus was characterized as sweet and cold nature, targeting the lung and stomach meridians, with uses evolving from clearing heat and resolving phlegm to nourishing Yin, moistening dryness, and relaxing tendons and unblocking meridians. Modern descriptions classify it as sweet, bitter, and cold in nature, affecting the heart, liver, and lung meridians, with functions including clearing heat, resolving phlegm, and facilitating orifices. It is indicated for conditions such as stroke with phlegm confusion, lung heat with phlegm congestion, convulsions, epilepsy, excessive phlegm in febrile diseases, high fever with thirst, irritability during pregnancy, and tetanus, with more clearly defined applications. Based on the results of the research, it is recommended that when developing and utilizing famous classical formulas containing Bambusae Succus, the one-year-old Phyllostachys nigra var. Henonis, which has been highly praised throughout history, should be selected as the source material. Industrial production should adopt the dry distillation method. Furthermore, in-depth research should be conducted on the modern technological characterization of the traditional quality control indicator of sweet taste, and reasonable modern quality control standards should be established.
3.Development of DUS testing guidelines for new Atractylodes lancea varieties.
Cheng-Cai ZHANG ; Ming QIN ; Xiu-Zhi GUO ; Zi-Hua ZHANG ; Hao-Kuan ZHANG ; Xiao-Yu DAI ; Sheng WANG ; Lan-Ping GUO
China Journal of Chinese Materia Medica 2025;50(6):1515-1523
Atractylodes lancea is a perennial herbaceous plant of Asteraceae, with rhizomes for medical use. However, A. lancea plants from different habitats have great variability, and the germplasm resources of A. lancea are unclear and mixed during production. Therefore, it is urgent to protect new varieties of A. lancea. The distinctness, uniformity, and stability(DUS) testing of new plant varieties is the foundation of plant variety protection, and the DUS testing guidelines are the technical basis for variety approval agencies to conduct DUS testing. In this study, the phenotypic traits of 94 germplasm accessions of A. lancea were investigated considering the breeding and variety characteristics of A. lancea in China. The traits were classified and described, and 24 traits were preliminarily determined, including 20 basic traits that must be tested and four traits selected to be tested. The 20 basic traits included 3 quality traits, 5 false quality traits, and 12 quantitative traits, corresponding to 1 plant traits, 2 stem traits, 8 leaf traits, 6 flower traits, and 3 seed traits. The measurement ranges and coefficients of variation of eight quantitative traits were determined, on the basis of which the grading criteria and codes of the traits were determined and assigned. The guidelines has guiding significance for the trait evaluation, utilization, and breeding of new varieties of A. lancea.
Atractylodes/growth & development*
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China
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Phenotype
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Guidelines as Topic
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Plant Breeding
4.Knockdown of human-specific lncRNA MEK6-AS1 improves osteogenic differentiation of senescent mesenchymal stem cells
Yunhua CHEN ; Di LI ; Xiaoyan ZHAO ; Ming CHEN ; Hongling LI ; Chunhua ZHAO
Basic & Clinical Medicine 2025;45(5):568-574
Objective To investigate the role of a novel human-specific long noncoding RNA(lncRNA),MEK6-AS1,and its potential molecular mechanism in improving the osteogenic differentiation of senescent mesenchymal stem cells(MSCs).Methods An in vitro human MSCs replicative senescence model was established by sequen-tial passaging,and then senescence was identified by β staining and senescence-related gene expression.RT-qPCR was used to detect the expression of MEK6-AS1 during senescence and osteogenic differentiation of human MSCs(hMSCs);Lentiviral knockdown technology was used to regulate the expression of MEK6-AS1 in the MSCs replicative senescence model.Transcriptome sequencing technology was utilized to analyze the effects of MEK6-AS1 on the transcriptome of hMSCs especially on genes and pathways related to osteogenic differentiation.The effect of MEK6-AS1 as an intervention target at osteogenic differentiation of human senescent hMSCs was evaluated with alkaline phosphatase staining microscopy.PCR technology was used to detect osteogenic gene expression levels in cells.Results With aging process,the osteogenic differentiation ability of hMSCs decreased significantly while the expression level of MEK6-AS1 was enhanced(P<0.000 1).Knockdown of MEK6-AS1 significantly enhanced the osteogenic differentiation of MSCs by the up-regulating expression of osteogenic markers and increasing minerali-zation capacity(P<0.001).Conclusions Knockdown of human-specific lncRNA MEK6-AS1 improves osteogenic differentiation of senescent MSCs,providing a new target and theoretical basis for the treatment of senescence-asso-ciated osteoporosis.
5.Transzonal Projections and Follicular Development Abnormalities in Polycystic Ovary Syndrome
Di CHENG ; Yu-Hua CHEN ; Xia-Ping JIANG ; Lan-Yu LI ; Yi TAN ; Ming LI ; Zhong-Cheng MO
Progress in Biochemistry and Biophysics 2025;52(10):2499-2511
Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder affecting a substantial proportion of women of reproductive age. It is frequently associated with ovulatory dysfunction, infertility, and an increased risk of chronic metabolic diseases. A hallmark pathological feature of PCOS is the arrest of follicular development, closely linked to impaired intercellular communication between the oocyte and surrounding granulosa cells. Transzonal projections (TZPs) are specialized cytoplasmic extensions derived from granulosa cells that penetrate the zona pellucida to establish direct contact with the oocyte. These structures serve as essential conduits for the transfer of metabolites, signaling molecules (e.g., cAMP, cGMP), and regulatory factors (e.g., microRNAs, growth differentiation factors), thereby maintaining meiotic arrest, facilitating metabolic cooperation, and supporting gene expression regulation in the oocyte. The proper formation and maintenance of TZPs depend on the cytoskeletal integrity of granulosa cells and the regulated expression of key connexins, particularly CX37 and CX43. Recent studies have revealed that in PCOS, TZPs exhibit significant structural and functional abnormalities. Contributing factors—such as hyperandrogenism, insulin resistance, oxidative stress, chronic inflammation, and dysregulation of critical signaling pathways (including PI3K/Akt, Wnt/β‑catenin, and MAPK/ERK)—collectively impair TZP integrity and reduce their formation. This disruption in granulosa-oocyte communication compromises oocyte quality and contributes to follicular arrest and anovulation. This review provides a comprehensive overview of TZP biology, including their formation mechanisms, molecular composition, and stage-specific dynamics during folliculogenesis. We highlight the pathological alterations in TZPs observed in PCOS and elucidate how endocrine and metabolic disturbances—particularly androgen excess and hyperinsulinemia—downregulate CX43 expression and impair gap junction function, thereby exacerbating ovarian microenvironmental dysfunction. Furthermore, we explore emerging therapeutic strategies aimed at preserving or restoring TZP integrity. Anti-androgen therapies (e.g., spironolactone, flutamide), insulin sensitizers (e.g., metformin), and GLP-1 receptor agonists (e.g., liraglutide) have shown potential in modulating connexin expression and enhancing granulosa-oocyte communication. In addition, agents such as melatonin, AMPK activators, and GDF9/BMP15 analogs may promote TZP formation and improve oocyte competence. Advanced technologies, including ovarian organoid models and CRISPR-based gene editing, offer promising platforms for studying TZP regulation and developing targeted interventions. In summary, TZPs are indispensable for maintaining follicular homeostasis, and their disruption plays a pivotal role in the pathogenesis of PCOS-related folliculogenesis failure. Targeting TZP integrity represents a promising therapeutic avenue in PCOS management and warrants further mechanistic and translational investigation.
6.Clinical characteristics of 33 patients with eosinophilic granulomatosis with polyangiitis
Ming-lang ZHAN ; Lin-di JIANG ; Yun LIU
Fudan University Journal of Medical Sciences 2025;52(1):77-82
Objective To provide a comprehensive description and summary of the clinical characteristics of eosinophilic granulomatosis with polyangiitis(EGPA)in order to enhance understanding of this disease.Methods A total of 33 EGPA patients treated in Zhongshan Hospital,Fudan University,between Jan 2017 and Aug 2022 were included in this retrospective analysis.The diagnosis was based on the 1990 American College of Rheumatology(ACR)classification criteria for EGPA.Clinical manifestations,laboratory examinations,and treatment outcomes of the patients were analyzed.Results Among the 33 EGPA patients,there were 22 males(66.7%)and 11 females(33.3%),with an average age of diagnosis being(47.42±15.83)years old.The most common initial department visited by patients was the rheumatology department(23 cases,69.7%),followed by the respiratory medicine department(6 cases,18.2%).Skin involvement manifested as rash,ulcers,necrosis or gangrene was observed in most cases(23 cases,69.7%),followed by asthma(17 cases,51.5%),infiltrative pneumonia(14 cases,42.4%),peripheral neuropathy(9 cases,27.3%),thrombosis formation(9 cases,27.3%).The mean absolute value of eosinophils in all patients was measured as(3.43±3.52)×109/L,with eight patients(24.2%)testing positive for antineutrophil cytoplasmic antibody(ANCA).Compared with ANCA-negative patients,ANCA-positive individuals exhibited significantly higher Birmingham Vasculitis Activity Score(BVAS)and eosinophil count,as well as a higher incidence rate of renal involvement(P<0.05).Glucocorticoid therapy was administered in thirty-two patients(97%),while biologics or tofacitinib were given to eleven patients(33.3%),among them six received tofacitinib treatment,of which five achieved disease remission.Conclusion EGPA exhibits a wide range of clinical manifestations,and ANCA-positive patients tend to exhibit higher disease activity levels.A multidisciplinary diagnosis and treatment system for EGPA should be established.
7.Risk factors and their predictive efficacy for early postoperative complications in elderly patients with hip fracture
Deen WAN ; Yongzhou YAN ; Feng SHUANG ; Hao LI ; Zhi ZENG ; Mudan HUANG ; Lu HAN ; Xiang PENG ; Di YANG ; Ming CHEN ; Qixin LIU
Chinese Journal of Trauma 2025;41(3):274-281
Objective:To investigate the risk factors and their predictive efficacy for early postoperative complications in elderly patients with hip fracture.Methods:A retrospective cohort study was conducted on the clinical data of 203 elderly patients with hip fracture admitted to the 908th Hospital of the Joint Logistics Support Force of the PLA and the First Affiliated Hospital of Nanchang University from January 2022 to December 2023, including 54 males and 149 females, aged 65-100 years [(80.5±7.7)years]. There were 96 patients with femoral neck fracture and 107 patients with intertrochanteric fracture. According to the AO/OTA classification, the fracture was classified as type 31A in 107 patients and type 31B in 96. Among them, 81 patients were treated with proximal femoral nail antirotation (PFNA), 65 with semi-hip arthroplasty, 52 with total hip arthroplasty (THA), and 5 with closed reduction and cannulated nail internal fixation. The patients were divided into complication group ( n=65) and non-complication group ( n=138) according to whether complications (mainly including delirium, lung infection, stress ulcer, and deep vein thrombosis of the lower limbs) occurred within 15 days after surgery. The gender, age, age stage, educational level, cause of injury, associated underlying diseases before surgery, AO/OTA classification, American Society of Anesthesiologists (ASA) classification, 5-factor modified frailty index (mFI-5) score, prognostic nutritional index (PNI), anesthesia method, operation method, operation time, intraoperative blood loss, length of hospital stay, etc., were recorded in the two groups. Univariate analysis and multivariate binary logistic regression analysis were used to evaluate the correlation between the above indexes and the occurrence of early postoperative complications in elderly patients with hip fracture and to determine their independent risk factors. The receiver operating characteristic (ROC) curve was plotted and the area under the curve (AUC) was calculated to evaluate the predictive efficacy of each risk factor for the occurrence of early postoperative complications in elderly patients with hip fracture. Results:Univariate analysis showed a certain correlation between age, age stage, associated underlying diseases before surgery, AO/OTA classification, ASA classification, mFI-5 score, PNI, operation method, and length of hospital stay and the occurrence of early postoperative complications in elderly patients with hip fracture ( P<0.05), while gender, educational level, cause of injury, anesthesia method, operation time, and intraoperative blood loss were not correlated with the occurrence of early postoperative complications in elderly patients with hip fracture ( P>0.05). The results of multivariate binary logistic regression analysis showed that the associated underlying diseases before surgery ( OR=5.46, 95% CI 1.33, 22.39, P<0.05), mFI-5 score ( OR=15.90, 95% CI 5.36, 47.15, P<0.01), and PNI ( OR=0.70, 95% CI 0.60, 0.81, P<0.01) were significantly correlated with the occurrence of early postoperative complications in elderly patients with hip fracture. The results of ROC curve analysis showed that mFI-5 score (AUC=0.85, 95% CI 0.80, 0.91) and PNI (AUC=0.87, 95% CI 0.82, 0.93) had moderate predictive efficacy, while the early warning efficacy of associated underlying diseases was low (AUC=0.54, 95% CI 0.45, 0.62). The combination of the above risk factors was more effective in predicting early postoperative complications in elderly patients with hip fracture (AUC=0.95, 95% CI 0.92, 0.98). Conclusions:The mFI-5 score, PNI, and associated underlying diseases before surgery are independent risk factors for early postoperative complications in elderly patients with hip fracture. The mFI-5 score and PNI have a higher predictive efficacy than associated diseases before surgery on the occurrence of early postoperative complications in elderly patients with hip fracture, while the combination of the above risk factors provides a significantly better predictive performance.
8.Evodiamine modulation of FOXM1 expression promotes apoptosis in colon cancer resistant cells HCT8/5-FU
Jing MA ; Di-long CHEN ; Yuan-yuan WAN ; Jia-ming HE ; An CHEN ; Yun-ying LI ; Hui-min WANG ; Jing LI
Chinese Pharmacological Bulletin 2025;41(1):35-43
Aim To study the effect of evodiamine(EVO)regulating forkhead box protein Ml(FOXM1)on the proliferation and apoptosis of colorectal cancer-resistant cells HCT8/5-FU.Methods CCK-8 assay and EdU assay were used to detect the effect of EVO on cell proliferation ability.Clone formation assay was employed to detect the effect of EVO on the clone for-mation ability of cells.Flow cytometric counting was applied to detect apoptosis.Western blot was utilized to detect the expression of cellular Bcl-2,Bax,FOXM1,β-catenin,c-MYC,and CyclinD1;Molecular docking was used to explore the EVO-FOXM1 interac-tion.Nude mouse transplant tumor model was estab-lished to validate the effect of EVO on HCT8/5-FU cells in vivo.Results CCK-8 assay showed that EVO inhibited the proliferation of HCT8/5-FU cells in a time-and concentration-dependent manner.EdU assay found that the newly proliferated cells in the EVO-trea-ted group were significantly reduced.The results of the clone formation assay showed that EVO inhibited the clone-forming ability of HCT8/5-FU cells.Flow cyto-metric counting found that apoptosis rate of the cells in the EVO group significantly increased.Western blot showed that FOXM1 and β-catenin were significantly highly expressed in HCT8/5-FU cells,and EVO down-regulated the expression of FOXM1,β-cateniin,c-MYC,CyclinD1,and Bcl-2,and up-regulated the ex-pression of Bax.Molecular docking revealed strong in-teractions between EVO and FOXM1.The in vivo ex-perimental results demonstrated that EVO exerted a substantial inhibitory effect on the growth of subcutane-ously implanted HCT8/5-FU xenograft tumors and regulated the expression of related proteins.HE stai-ning revealed significant nuclear consolidation and fragmentation of tumor cells in the EVO group.Con-clusions The findings suggest that EVO could sup-press the activation of the Wnt signaling pathway through a mechanism involving the downregulation of FOXM1 protein expression,thus inhibiting the prolifer-ation of HCT8/5-FU cells and induce their apoptosis.
9.Complete genomic sequence analysis of the G6P1bovine rotavirus BLL strain
Jin-hua ZHANG ; Xia-fei LIU ; Jun-jie YU ; Jia-xin FAN ; Ming-yue WANG ; Guang-ping XIONG ; Yi-peng WANG ; Dan-di LI ; Xiao-man SUN ; Li-li PANG ; Zhao-jun DUAN
Chinese Journal of Zoonoses 2025;41(1):8-14
Bovine rotavirus(BRV)is an important pathogen causing diarrhea in calves.To understand the genomic charac-teristics and genetic variations in bovine rotavirus,and to further enrich data on the biological characteristics of rotavirus,we aimed to amplify 11 gene segments of the isolated and cultured G6P[1]bovine rotavirus BLL strain,perform whole genome se-quencing,and analyze the molecular characteristics.MEGA7.0 and DNAMAN software were used for homology and typing a-nalysis,and the whole genome phylogenetic tree was constructed to analyze genetic evolution relationships.The complete geno-type of the BLL strain was G6-P[1]-I2-R2-C2-M2-A3-N2-T6-E2-H3.Phylogenetic analysis of the VP7 and VP4 genes of the BLL strain showed that the VP7 gene had the highest homology with RVA/Cow-wt/HB01/China/2021,and the VP4 gene of the BLL strain was in the same branch as RVA/Human-tc/ISR/Ro8059/1995.From the sequence alignment of VP8*amino acids,the sialic acid domain of the BLL strain was found to be similar to that in other P[1]strains,but different from those in other types of strains,except for residue 189,which was the same as that in Ro8059 but different from that in other strains.The results suggested that the BLL strain might potentially infect humans.Therefore,continued monitoring and study of the biological characteristics of this strain are necessary to provide more information and evidence supporting further research on the cross-species transmission of group A rotavirus in China.
10.Drug resistance characteristics and whole genome polymorphisms of group A Streptococcus in Jiangsu Province during 2016 to 2023
Jie HONG ; Hao-di HUANG ; Ke XU ; Zhong-ming TAN ; Hui-min QIAN ; Jie-fu PENG ; Xiao-xiao KONG
Chinese Journal of Zoonoses 2025;41(1):40-46
This study was aimed at understanding the relationships among the drug resistance and genome characteristics of group A Streptococcus in Jiangsu Province.A total of 149 group A Streptococcus strains were collected from hospitals between 2016 and 2023.Thirteen antimicrobial minimal inhibitory concentrations were detected with the micro-dilution broth method.The GAS strains were typed with emm genotyping analysis and whole genome sequencing,to determine the carriage rates of drug resistance genes and the evolutionary relationships among strains.The resistance rates of 149 GAS strains to erythromy-cin,tetracycline,and clindamycin exceeded 90%,whereas the strains showed sensitivity to 8 different antibiotics,including penicillin.Notably,the resistance rates to erythromycin,tetracycline,and clindamycin consistently increased over time.All strains were classified into 9 emm types,among which emm12 accounted for the highest proportion(77/149;51.68%).Signifi-cant statistical differences were observed among emm types,in terms of the drug resistance rate,number of resistant species,and prevalence of drug resistance genes.Furthermore,SNP evolutionary tree analysis revealed 3 distinct clusters within the GAS strains:emm12,emm1,and other emm types.emm 12 and emm1 were the dominant GAS strains in Jiangsu Province.Most isolates were resistant to erythromycin,tetracycline,and clindamycin.Differences in phenotypes and genomic characteris-tics were observed among emm types.

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