1.Chinese clinical expert consensus on multi-arm robotic-assisted uniportal pulmonary resection
Deping ZHAO ; Xuefei HU ; Chenlu YANG ; Ye NING ; Yuming ZHU ; Lei JIANG ; Wenxin HE ; Chang CHEN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(09):1370-1374
Multi-arm robotic-assisted uniportal pulmonary resection is an emerging minimally invasive technique that enables anatomical pulmonary resection through a single incision using a multi-arm robotic platform. This consensus was initiated by Shanghai Pulmonary Hospital and developed through a multidisciplinary national expert panel. Using evidence-based methodology and expert survey, it provides a comprehensive overview of the clinical application of this technique, including its definition, indications and contraindications, technical considerations, and learning curve. As the first expert consensus focused on multi-arm robotic-assisted uniportal pulmonary resection, this consensus highlights the feasibility and developmental potential of the technique, which integrates existing robotic systems with uniportal minimally invasive principles. The consensus also offers theoretical and practical guidance for the standardized and safe implementation of the technique.
2.Mesenchymal stem cells and their derived extracellular vesicles target macrophages to intervene in autoimmune diseases
Lanxuan YAO ; Xuefei WANG ; Yang LIU ; Yujia YANG ; Yi ZHAO ; Fangfang QI ; Yinghui LI
Chinese Journal of Tissue Engineering Research 2025;29(31):6772-6781
BACKGROUND:Macrophages are an important part of innate immunity.When the internal environment of the body changes,macrophages can produce different polarization phenotypes and play the corresponding inflammatory immune function.Mesenchymal stem cells can secrete a large number of extracellular vesicles into the internal environment of the body,which have the functions of intercellular signaling and immune regulation.Studies have shown that mesenchymal stem cells and mesenchymal stem cells-extracellular vesicles can affect the M1/M2 polarization balance of macrophages so as to treat immune inflammatory diseases.OBJECTIVE:To explore the signaling mechanism of how mesenchymal stem cells and their extracellular vesicles interfere with autoimmune diseases by regulating the polarization of macrophages,as well as the related research progress of engineered extracellular vesicles in this field.METHODS:The first author searched the relevant literature published in PubMed,CNKI and other databases until June 2024.Chinese search terms were"mesenchymal stem cells,extracellular vesicles,exosomes,apoptotic bodies,apoptotic vesicles,macrophage polarization,M1 polarization,M2 polarization,autoimmune diseases,multiple sclerosis,rheumatoid arthritis,systemic lupus erythematosus,type 1 diabetes mellitus,inflammatory bowel disease,autoimmune dacryadenitis,engineered extracellular vesicles,engineering exosomes,drug delivery."English search terms were"macrophage polarization,M1 macrophage,M2 macrophage,autoimmune disease,type 1 diabetes,multiple sclerosis,rheumatoid arthritis,systemic lupus erythematosus,autoimmune dacryadenitis,inflammatory bowel disease,mesenchymal stem cells,extracellular vesicles,engineered extracellular vesicles,engineering exosomes,drug delivery."The title and abstract of each paper were read and initially screened.Finally,70 articles were selected for induction and analysis.RESULTS AND CONCLUSION:(1)Mesenchymal stem cells can regulate M1/M2 polarization by releasing or indirectly acting on functional proteins.(2)Mesenchymal stem cells can regulate macrophage M2 polarization through inflammasome.(3)Mesenchymal stem cells can be combined with commonly used drugs to enhance drug efficacy.(4)Mesenchymal stem cells can regulate the release of mesenchymal stem cells-extracellular vesicles after inflammatory stimulation and affect the polarization of macrophages.(5)Mesenchymal stem cells-extracellular vesicles can regulate autoimmune diseases by targeting macrophage polarization through PTEN,NOTCH,nuclear factor κB,Toll-like receptors,PI3K/AKT and other pathways.(6)Engineered extracellular vesicles can achieve non-invasive targeted drug delivery,prolong the half-life of drugs,promote the oral administration of exosomes,reduce allograft reaction,improve the bioavailability of Chinese herbs and overcome the blood-brain barrier,opening up a new path for drug delivery.
3.Emd-D inhibited ovarian cancer progression via PFKFB4-dependent glycolysis and apoptosis.
Xin ZHAO ; Chao CHEN ; Xuefei FENG ; Haoqi LEI ; Lingling QI ; Hongxia ZHANG ; Haiying XU ; Jufeng WAN ; Yan ZHANG ; Baofeng YANG
Chinese Journal of Natural Medicines (English Ed.) 2025;23(4):431-442
Ovarian cancer poses a significant threat to women's health, necessitating effective therapeutic strategies. Emd-D, an emodin derivative, demonstrates enhanced pharmaceutical properties and bioavailability. In this study, Cell Counting Kit 8 (CCK8) assays and Ki-67 staining revealed dose-dependent inhibition of cell proliferation by Emd-D. Migration and invasion experiments confirmed its inhibitory effects on OVHM cells, while flow cytometry analysis demonstrated Emd-D-induced apoptosis. Mechanistic investigations elucidated that Emd-D functions as an inhibitor by directly binding to the glycolysis-related enzyme PFKFB4. This was corroborated by alterations in intracellular lactate and pyruvate levels, as well as glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) expression. PFKFB4 overexpression experiments further supported the dependence of Emd-D on PFKFB4-mediated glycolysis and SRC3/mTORC1 pathway-associated apoptosis. In vivo experiments exhibited reduced xenograft tumor sizes upon Emd-D treatment, accompanied by suppressed glycolysis and increased expression of Bax/Bcl-2 apoptotic proteins within the tumors. In conclusion, our findings demonstrate Emd-D's potential as an anti-ovarian cancer agent through inhibition of the PFKFB4-dependent glycolysis pathway and induction of apoptosis. These results provide a foundation for further exploration of Emd-D as a promising drug candidate for ovarian cancer treatment.
Female
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Humans
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Ovarian Neoplasms/physiopathology*
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Phosphofructokinase-2/genetics*
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Apoptosis/drug effects*
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Glycolysis/drug effects*
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Animals
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Cell Line, Tumor
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Mice
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Cell Proliferation/drug effects*
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Emodin/administration & dosage*
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Mice, Nude
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Mice, Inbred BALB C
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Hexokinase/metabolism*
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Xenograft Model Antitumor Assays
4.Changing antimicrobial resistance profiles of Burkholderia cepacia in hospitals across China:results from CHINET Antimicrobial Resistance Surveillance Program,2015-2021
Chunyue GE ; Yunjian HU ; Xiaoman AI ; Yang YANG ; Fupin HU ; Demei ZHU ; Yingchun XU ; Xiaojiang ZHANG ; Hui LI ; Ping JI ; Yi XIE ; Mei KANG ; Chuanqing WANG ; Pan FU ; Yuanhong XU ; Ying HUANG ; Ziyong SUN ; Zhongju CHEN ; Yuxing NI ; Jingyong SUN ; Yunzhuo CHU ; Sufei TIAN ; Zhidong HU ; Jin LI ; Yunsong YU ; Jie LIN ; Bin SHAN ; Yan DU ; Sufang GUO ; Lianhua WEI ; Fengmei ZOU ; Hong ZHANG ; Chun WANG ; Chao ZHUO ; Danhong SU ; Dawen GUO ; Jinying ZHAO ; Hua YU ; Xiangning HUANG ; Wen'en LIU ; Yanming LI ; Yan JIN ; Chunhong SHAO ; Xuesong XU ; Chao YAN ; Shanmei WANG ; Yafei CHU ; Lixia ZHANG ; Juan MA ; Shuping ZHOU ; Yan ZHOU ; Lei ZHU ; Jinhua MENG ; Fang DONG ; Zhiyong LÜ ; Fangfang HU ; Han SHEN ; Wanqing ZHOU ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Jihong LI ; Jinju DUAN ; Jianbang KANG ; Xiaobo MA ; Yanping ZHENG ; Ruyi GUO ; Yan ZHU ; Yunsheng CHEN ; Qing MENG ; Shifu WANG ; Xuefei HU ; Jilu SHEN ; Wenhui HUANG ; Ruizhong WANG ; Hua FANG ; Bixia YU ; Yong ZHAO ; Ping GONG ; Kaizhen WENG ; Yirong ZHANG ; Jiangshan LIU ; Longfeng LIAO ; Hongqin GU ; Lin JIANG ; Wen HE ; Shunhong XUE ; Jiao FENG ; Chunlei YUE
Chinese Journal of Infection and Chemotherapy 2025;25(5):557-562
Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1%(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5%,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3%(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1%)were isolated from sputum and respiratory secretions,followed by urine(10.7%)and blood samples(8.1%).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1%.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4%in the patients<18 years old to 20.6%in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.
5.Changing prevalence and antibiotic resistance profiles of carbapenem-resistant Enterobacterales in hospitals across China:data from CHINET Antimicrobial Resistance Surveillance Program,2015-2021
Wenxiang JI ; Tong JIANG ; Jilu SHEN ; Yang YANG ; Fupin HU ; Demei ZHU ; Yuanhong XU ; Ying HUANG ; Fengbo ZHANG ; Ping JI ; Yi XIE ; Mei KANG ; Chuanqing WANG ; Pan FU ; Yingchun XU ; Xiaojiang ZHANG ; Ziyong SUN ; Zhongju CHEN ; Yuxing NI ; Jingyong SUN ; Yunzhuo CHU ; Sufei TIAN ; Zhidong HU ; Jin LI ; Yunsong YU ; Jie LIN ; Bin SHAN ; Yan DU ; Sufang GUO ; Lianhua WEI ; Fengmei ZOU ; Yunjian HU ; Xiaoman AI ; Chao ZHUO ; Danhong SU ; Dawen GUO ; Jinying ZHAO ; Hua YU ; Xiangning HUANG ; Wen'en LIU ; Yanming LI ; Yan JIN ; Chunhong SHAO ; Xuesong XU ; Chao YAN ; Shanmei WANG ; Yafei CHU ; Lixia ZHANG ; Juan MA ; Shuping ZHOU ; Yan ZHOU ; Lei ZHU ; Jinhua MENG ; Fang DONG ; Zhiyong LÜ ; Fangfang HU ; Han SHEN ; Wanqing ZHOU ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Jihong LI ; Jinju DUAN ; Jianbang KANG ; Xiaobo MA ; Yanping ZHENG ; Ruyi GUO ; Yan ZHU ; Yunsheng CHEN ; Qing MENG ; Shifu WANG ; Xuefei HU ; Hong ZHANG ; Chun WANG ; Wenhui HUANG ; Ruizhong WANG ; Hua FANG ; Bixia YU ; Yong ZHAO ; Ping GONG ; Kaizhen WENG ; Yirong ZHANG ; Jiangshan LIU ; Longfeng LIAO ; Hongqin GU ; Lin JIANG ; Wen HE ; Shunhong XUE ; Jiao FENG ; Chunlei YUE
Chinese Journal of Infection and Chemotherapy 2025;25(4):445-454
Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43%(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38%,9.73%,and 8.47%,respectively.The prevalence of CRE strains in Escherichia coli was 1.99%.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)%,followed by blood(20.88±3.40)%and urine(18.40±3.45)%.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)%.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.
6.Changing distribution and antibiotic resistance profiles of the respiratory bacterial isolates in hospitals across China:data from CHINET Antimicrobial Resistance Surveillance Program,2015-2021
Ying FU ; Yunsong YU ; Jie LIN ; Yang YANG ; Fupin HU ; Demei ZHU ; Yingchun XU ; Xiaojiang ZHANG ; Fengbo ZHANG ; Ping JI ; Yi XIE ; Mei KANG ; Chuanqing WANG ; Pan FU ; Yuanhong XU ; Ying HUANG ; Ziyong SUN ; Zhongju CHEN ; Yuxing NI ; Jingyong SUN ; Yunzhuo CHU ; Sufei TIAN ; Zhidong HU ; Jin LI ; Bin SHAN ; Yan DU ; Sufang GUO ; Lianhua WEI ; Fengmei ZOU ; Hong ZHANG ; Chun WANG ; Yunjian HU ; Xiaoman AI ; Chao ZHUO ; Danhong SU ; Dawen GUO ; Jinying ZHAO ; Hua YU ; Xiangning HUANG ; Wen'en LIU ; Yanming LI ; Yan JIN ; Chunhong SHAO ; Xuesong XU ; Chao YAN ; Shanmei WANG ; Yafei CHU ; Lixia ZHANG ; Juan MA ; Shuping ZHOU ; Yan ZHOU ; Lei ZHU ; Jinhua MENG ; Fang DONG ; Zhiyong LÜ ; Fangfang HU ; Han SHEN ; Wanqing ZHOU ; Wei JIA ; Gang LI ; Jinsong WU ; Yuemei LU ; Jihong LI ; Jinju DUAN ; Jianbang KANG ; Xiaobo MA ; Yanping ZHENG ; Ruyi GUO ; Yan ZHU ; Yunsheng CHEN ; Qing MENG ; Shifu WANG ; Xuefei HU ; Jilu SHEN ; Ruizhong WANG ; Hua FANG ; Bixia YU ; Yong ZHAO ; Ping GONG ; Kaizhen WENG ; Yirong ZHANG ; Jiangshan LIU ; Longfeng LIAO ; Hongqin GU ; Lin JIANG ; Wen HE ; Shunhong XUE ; Jiao FENG ; Chunlei YUE ; Wenhui HUANG
Chinese Journal of Infection and Chemotherapy 2025;25(4):431-444
Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6%of the isolates were Gram-negative bacteria and 17.4%were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)%and(94.0±0.1)%,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P<0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9%.The prevalence of penicillin-resistant S.pneumoniae was 1.4%.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8%and 41.3%,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7%,20.8%,9.4%,29.8%,and 73.3%,respectively.The prevalence of β-lactamase was 96.1%in Moraxella catarrhalis and 60.0%in Haemophilus influenzae.The H.influenzae isolates from children(<18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P<0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.
7.Feasibility study of a novel three-dimensional small intestinal submucosa patch in porcine hiatal hernia repair
Minxian ZHAO ; Xuefei ZHAO ; Pu WANG ; Pengfei WEI ; Yusheng NIE ; Huiqi YANG
Chinese Journal of General Surgery 2025;34(10):2168-2179
Background and Aims:Laparoscopic hiatal hernia repair(LHHR)is the gold-standard surgical treatment for hiatal hernia(HH),but postoperative recurrence remains a challenge due to hiatal enlargement and disruption of the phrenoesophageal ligament.This study aimed to assess the feasibility,safety,and short-term efficacy of a novel three-dimensional small intestinal submucosa(3D-SIS)patch designed for circumferential crural reinforcement and ligament-like reconstruction in a porcine LHHR model.Methods:Twelve healthy pigs(35-40 kg)were equally randomized into non-mesh group,SIS flat patch group,and 3D-SIS patch group.All animals underwent LHHR and Nissen fundoplication under general anesthesia.In the non-mesh group,the hiatal defect was closed with interrupted sutures.In the SIS flat patch group,a U-shaped SIS patch was placed posterior to the esophagus to reinforce the crura and fixed with medical glue.In the 3D-SIS patch group,an intraoperatively assembled three-dimensional patch was applied,consisting of an upper keyhole-shaped layer for circumferential diaphragmatic reinforcement,a tubular middle part encircling the abdominal esophagus,and a lower small keyhole-shaped patch covering the gastroesophageal junction,all fixed with medical glue.After 3 months,laparotomy was performed to assess recurrence,patch integration,and complications,followed by biomechanical and histological evaluations.Results:All procedures were completed successfully with no deaths or major complications.Operative time was slightly longer in the patch groups,while blood loss was similar.No hernia recurrence or patch migration was observed at 3 months.Biomechanical testing revealed higher ultimate load and Young's modulus in both SIS groups than in the non-mesh group.Histological analysis demonstrated neovascularization and collagen deposition in the patch groups,with the 3D-SIS patch showing more complete circumferential integration and ligament-like tissue formation.Conclusion:The 3D-SIS patch is feasible and safe in porcine LHHR.It provides circumferential diaphragmatic reinforcement and promotes phrenoesophageal ligament-like regeneration,offering a new concept for reducing postoperative recurrence and reconstructing the anti-reflux barrier.
8.Evaluation progress of the application of staplers in thoracoscopic lung surgery
Shenghui LI ; Yijiu REN ; Hang SU ; Minglei YANG ; Guofang ZHAO ; Yongxiang SONG ; Xuefei HU ; Deping ZHAO ; Qi XUE ; Chang CHEN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(05):709-713
Compared to traditional suturing, lung stapling using automatic staplers offers advantages such as smaller trauma, faster wound healing, ease of operation, and lower complication rates, making it widely used in clinical practice. However, there are significant differences in bronchial tissue thickness at different anatomical locations, and the market is flooded with various types of staplers. Currently, there is a lack of recommended stapling schemes for bronchial staplers at different anatomical locations. This article reviews the development and application of automatic staplers and summarizes some types of staplers that are currently used in clinical practice, with the aim of promoting the formation of individualized stapler selection protocols for minimally invasive thoracic surgery based on the Chinese population.
9.Evolution and genetic variation of HA and NA genes of H1N1 influenza virus in Shanghai, 2024
Lufang JIANG ; Wei CHU ; Xuefei QIAO ; Pan SUN ; Senmiao DENG ; Yuxi WANG ; Xue ZHAO ; Jiasheng XIONG ; Xihong LYU ; Linjuan DONG ; Yaxu ZHENG ; Yinzi CHEN ; Chenyan JIANG ; Chenglong XIONG ; Jian CHEN
Shanghai Journal of Preventive Medicine 2025;37(9):719-724
ObjectiveTo analyze the evolutionary characteristics and genetic variations of the HA (hemagglutinin) and NA (neuraminidase) genes of influenza A(H1N1) viruses in Shanghai during 2024, to investigate their transmission patterns, and to evaluate their potential impact on vaccine effectiveness. MethodsFrom January to October 2024, throat swab specimens were collected from influenza like illness (ILI) patients at 4 hospitals in Shanghai. Real-time fluorescence ploymerase chain reaction (RT-PCR) was used for virus detection and isolation of H1N1 influenza viruses. Forty influenza A(H1N1) virus strains were sequenced using Illumina NovaSeq 6000 platform, followed by phylogenetic analyses, genetic distance analysis, and amino acid variation analyses of HA and NA genes. ResultsPhylogenetic tree of the HA and NA genes revealed that the 40 influenza A(H1N1) virus strains circulating in Shanghai in 2024 exhibited no significant geographic clustering, with a broad origin of strains and complex transmission chains. Genetic distance analyses demonstrated that the average intra-group genetic distances of HA and NA genes among the Shanghai strains were 0.005 1±0.000 6 and 0.004 6±0.000 6, respectively, which were comparable to or higher than those observed in global surveillance strains. Both HA and NA genes displayed frequent mutations. Compared to the 2023‒2024 and 2024‒2025 Northern Hemisphere A(H1N1) vaccine strains (WHO-recommended), the HA proteins of 40 Shanghai strains exhibited amino acid substitutions at positions 120, 137, 142, 169, 216, 223, 260, 277, 356 and 451, with critical mutations at positions 137 and 142 located within the Ca2 antigenic determinant. Furthermore, mutations in the NA protein were observed at positions 13, 50, 200, 257, 264, 339 and 382. ConclusionThe genetic background of the 2024 Shanghai influenza A(H1N1) virus strains is complex and diverse, and antigenic variation may affect vaccine effectiveness. Therefore, it is recommended to enhance genomic surveillance of influenza viruses, evaluate vaccine suitability, and implement more targeted prevention and control strategies against imported influenza viruses.
10.Obesity-driven oleoylcarnitine accumulation in tumor microenvironment promotes breast cancer metastasis-like phenotype.
Chao CHEN ; Hongxia ZHANG ; Lingling QI ; Haoqi LEI ; Xuefei FENG ; Yingjie CHEN ; Yuanyuan CHENG ; Defeng PANG ; Jufeng WAN ; Haiying XU ; Shifeng CAO ; Baofeng YANG ; Yan ZHANG ; Xin ZHAO
Acta Pharmaceutica Sinica B 2025;15(4):1974-1990
Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.

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