Background/Aims: Regorafenib is recommended by guidelines and trials as a sequential second-line therapy following progression on first-line sorafenib or lenvatinib in hepatocellular carcinoma (HCC). However, efficacy is limited, highlighting the urgent need to screen suitable patients and develop sensitization strategies. Methods: Acquired sorafenib- or lenvatinib-resistant (SR or LR) HCC cell lines and organoids were established. Genome-wide CRISPR library screen was performed in SR or LR cell strains to identify synthetic lethal targets of regorafenib. RNA-seq and FITC-regorafenib efflux assay were used to elucidate ERBB3-driven downstream signaling. Preclinical mouse models of cell line- and patient-derived xenografts and clinical cohorts of HCC patients were employed to validate the efficacy of ERBB3-guided patient stratification. Results: Screening with CRISPR library, we showed that inhibition of ERBB3 was synthetic lethal with regorafenib in SR or LR cell strains and organoids. Mechanistically, SR or LR triggered feedback activation of ERBB3 signaling and mediated regorafenib efflux via ERBB3-HIF1A-ABCB1 cascade pathway, limiting sensitivity to regorafenib. Moreover, ERBB3-low tumors following SR or LR exhibited significant sensitivity to regorafenib, suggesting its potential as a predictive biomarker to screen optimal candidates for sequential therapy. Seribantumab, an ERBB3-targeting monoclonal antibody, inhibited ERBB3-HIF1A-ABCB1 cascade, and its combination with regorafenib exerted marked synergistic anti-tumor effects on ERBB3-high tumors resistant to sorafenib or lenvatinib both in vitro and in vivo. Conclusions This study revealed that ERBB3 was a key resistance factor driving limited efficacy to sequential regorafenib, but also an effective therapeutic target whose inhibition enhanced regorafenib sensitivity after SR or LR.

Background/Aims: Natural killer (NK) cell function is generally considered dampened in chronic hepatitis B virus (HBV) infection; however, the NK cell pool exhibits phenotypic and functional heterogeneity, and the antibody--mediated effect of NK cells remains less characterized. This study evaluated the dynamic changes in antibody-mediated NK cell responses and the involvement of distinct NK subsets across disease stages and during antiviral treatment. Methods: A T-cell receptor-like antibody specific for the HBV core 18–27 peptide (cTCRL-Ab) was used to determine the antibody-mediated effect of NK cells, and an array of NK cell surface markers were analyzed in cross-sectional and longitudinal cohorts of patients with chronic HBV infection. Single-cell RNA sequencing (scRNA-seq) was performed to identify the heterogeneity of NK subsets. Results: The cTCRL-Ab enabled the detection of NK cell cytolytic activity and IFNγ production. Notably, cTCRL-Ab-mediated NK cell responses were compromised in chronically HBV-infected patients, particularly in those receiving pegylated interferon-α (Peg-IFNα), which was associated with the downregulation of CD16 expression. Correspondingly, Peg-IFNα inhibited cTCRL-Ab-mediated NK cell function by reducing CD16 expression in vitro. scRNA-seq revealed that CD16 downregulation occurred mainly within a dysfunctional CD16hi NK subset exhibiting exhaustion properties. In contrast, an activated CD16hiNK subpopulation (CX3CR1⁺KLRC2–CD16hi) with high cytotoxicity was enriched in patients who experienced favorable treatment responses. Furthermore, the intrahepatic CX3CR1+KLRC2–CD16hi subset tended to exhibit functional restoration in HBsAg-loss individuals. Conclusions Our data contribute to the understanding of antibody-mediated responses of NK cells in chronic HBV infection, and highlight a previously unappreciated functional CX3CR1+KLRC2–CD16hiNK subset as a potential therapeutic target.

Lung cancer constitutes the most prevalent and lethal malignant tumor in China. Approximately 85% of lung cancer diagnoses correspond to the non-small cell histological subtype [non-small cell lung cancer (NSCLC)]. Despite surgery being the mainstay for early-stage disease, postoperative recurrence remains high and adjuvant chemotherapy offers limited benefit. In recent years, targeted therapy has demonstrated substantial advantages in driver mutation-positive NSCLC. To this end, the Lung Cancer Medical Education Committee of the Chinese Medical Education Association developed guidelines based on a systematic review of evidence through November 2025, using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach and a modified Delphi method. Focusing on epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), and addressing ROS proto-oncogene 1 (ROS1), B-Raf proto-oncogene serine/threonine kinase (BRAF) V600E mutation, and mesenchymal-epithelial transition factor (MET) exon 14 (METex14) skipping, the guideline covers molecular testing, neoadjuvant/adjuvant therapy, perioperative strategies, minimal residual disease monitoring, and postoperative surveillance. It defines testing requirements, specifies stage-directed and subtype-specific treatments, and standardizes minimal residual disease monitoring. These recommendations emphasize precision and feasibility to improve survival and quality of life.

From July 22 to 24, 2026, the 2nd International Symposium on Environment and Reproductive Health and the 20th National Postgraduates Symposium on Environmental and Occupational Medicine were successfully held in Shanghai. The conference brought together experts, scholars, young researchers, and graduate students from Harvard University, National University of Singapore, Chinese University of Hong Kong, Peking University, Fudan University, Shanghai Jiao Tong University, and other domestic and foreign universities and scientific research institutions to carry out in-depth exchanges on cutting-edge issues such as environment and reproductive health, environmental exposure and health effects, occupational health, disease risks, and toxicological mechanisms. The conference featured a main hall, multiple sessions, an editorial board memebers & experts forum, excellent paper reports, a postgraduate parallel forum, and keynote presentations. This postgraduate symposium, themed "Research and practice: Healing the schism", attracted a total of 113 papers. This year marked the first time that the National Postgraduates Symposium on Environmental and Occupational Medicine was jointly held with an international academic conference. It further expanded the high-level platform for academic exchange and young talent cultivating, and promoted the deep integration of scientific research innovation, achievement dissemination, and public health practice.

This study aimed to explore the molecular mechanism of rubioncolin C(RuC) in inhibiting gastric cancer(GC). AGS and MGC803 cell lines were selected as cellular models. After treating the cells with RuC at different concentrations, the effects of RuC on the proliferation ability of GC cells were assessed using the CCK-8 method, real-time cellular analysis(RTCA), and colony formation assays. Transmission electron microscopy was used to observe subcellular structural changes. Immunofluorescence was applied to detect LC3 fluorescent foci. Acridine orange staining was used to evaluate the state of intracellular lysosomes. Western blot was employed to detect the expression of autophagy-related proteins LC3Ⅱ, P62, and lysosomal cathepsin D(CTSD). The SuperPred online tool was used to predict the target proteins that bound to RuC, and molecular docking analysis was conducted to identify the interaction sites between RuC and CTSD. The drug affinity responsive target stability(DARTS) assay was performed to detect the direct binding interaction between RuC and CTSD. The results showed that RuC significantly inhibited the proliferation and colony formation of GC cells at low concentrations, with 24-hour half-maximal inhibitory concentrations(IC_(50)) of 3.422 and 2.697 μmol·L~(-1) for AGS and MGC803 cells, respectively. After 24 hours of treatment with RuC at concentrations of 1, 2, and 3 μmol·L~(-1), the colony formation rates for AGS cells were 61.0%±1.5%, 28.0%±0.5%, and 18.2%±0.5%, respectively, while the rates for MGC803 cells were 56.0%±0.5%, 23.3%±1.0%, and 11.8%±1.0%, all of which were significantly reduced. Transmission electron microscopy revealed that RuC promoted an increase in autophagosome formation in GC cells. Immunofluorescence detection showed that LC3 fluorescent foci of GC cells increased with the increase in RuC dose. RuC up-regulated the expression of autophagy-related proteins LC3Ⅱ and P62 in GC cells. Acridine orange staining indicated that RuC altered the acidic environment of lysosomes. SuperPred online prediction identified CTSD as a potential target protein of RuC. Western blot analysis revealed that RuC induced the up-regulation of the inactive precursor of CTSD in GC cells. CTSD activity assays indicated that RuC reduced the activity of CTSD. Molecular docking simulations found that RuC bound to the substrate-binding region of CTSD, forming hydrogen bonds with the Tyr205 and Asp231 residues. Microscale thermophoresis and DARTS assays further confirmed that RuC directly bound to CTSD. In summary, RuC inhibits lysosomal activity by targeting and down-regulating the expression of CTSD, thereby inducing autophagosome accumulation in GC cells.
Humans ; Stomach Neoplasms/enzymology* ; Cathepsin D/chemistry* ; Cell Line, Tumor ; Molecular Docking Simulation ; Cell Proliferation/drug effects* ; Autophagosomes/metabolism* ; Autophagy/drug effects*

Objective To evaluate the efficacy of intravascular intervention in the treatment of multiple intracranial aneurysms(MIAs).Methods The clinical data of MIAs patients,who were treated with intravascular intervention from December 2013 to December 2021 in Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,were collected and were analyzed by using statistical methods.Results A total of 105 MIAs patients were enrolled in this study,and among them 77 patients(73.3％)were complicated by subarachnoid haemorrhage.Intravascular intervention was performed for 192 of the 240(80.0％)intracranial aneurysms(I As),including 142 IAs receiving one-stage treatment and 50 IAs receiving multi-stage treatment.In 66 patients,all the IAs were treated.Simple spring coil embolization was performed for 84 IAs and stent-assisted spring coil embolization was carried out for 108 IAs.During the follow-up period,11 patients developed recurrent IAs,which received treatment again.There was no obvious statistical difference in the treatment results between the patients receiving one-stage treatment and the patients receiving multi-stage treatment(P＞0.05).There was also no obvious statistical difference in the follow-up findings and prognosis results between the patients receiving one-stage treatment and the patients receiving multi-stage treatment(P＞0.05).Conclusion For the treatment of MIAs,the clinical efficacy of one-stage intravascular treatment and multi-stage intravascular treatment is roughly the same.However,one-stage treatment should be adopted as far as possible when the technical conditions permit.

OBJECTIVE: To explore the current status, evolution, hot topics, and future research trends in the field of burn-related sepsis research through a visual analysis of literature. METHODS: A bibliometric method was employed to retrieve articles related to burn-related sepsis from January 1, 1994, to May 16, 2024, in the China National Knowledge Infrastructure (CNKI) and the Web of Science database. The CiteSpace 6.3.R1 software was used to analyze the retrieved literature. The number of publications, authors, countries, and institutions in both Chinese and English literature was statistically analyzed. Co-occurrence analysis, clustering analysis, and co-citation analysis of keywords were performed. RESULTS: A total of 1 090 articles from the CNKI database and 1 143 articles from the Web of Science database were retrieved. Over the past 20 years, the volume of Chinese publications has remained stable, although there has been a slight decline in the past two years. In contrast, the number of English publications, after a period of growth, showed a sharp decline over the past three years. In Chinese literature, 1 457 authors published articles on burn-related sepsis as first authors, with 14 core authors publishing four or more articles. In English literature, 98 authors published articles on burn-related sepsis as first authors. Research on burn-related sepsis was conducted by 76 countries, with the United States having the most collaborations and publications. Globally, 1 349 institutions published articles on burn-related sepsis, with the top institutions being the First Affiliated Hospital of the PLA General Hospital (8 articles) for Chinese literature and the University of Texas Medical Branch (57 articles) for English literature. In the co-occurrence analysis, 208 Chinese keywords and 211 English keywords were included. Excluding keywords related to search terms, the top five most frequent keywords in Chinese literature were burn, sepsis, infection, severe burn, and procalcitonin; the top five most frequent keywords in English literature were sepsis, septic shock, mortality, injury, and burn injury. Chinese keyword analysis identified six clusters, with the largest being sepsis, followed by procalcitonin, infection, and severe burn. English keyword analysis identified seven clusters, with the largest being expression, followed by epidemiology, inhalation injury, and acute kidney injury. The persistent clusters in Chinese literature were procalcitonin, with recent emerging nodes being severe burn, inflammatory response, platelets, and predictive value. In English literature, the persistent clusters were inhalation injury and nitric oxide, with recent emerging nodes being continuous renal replacement therapy, hemorrhagic shock, and early enteral nutrition. The longest-lasting emergent keyword in Chinese literature was delayed resuscitation (2003-2010), with the highest emergent strength being severe burn. In English literature, the longest-lasting emergent keywords, each lasting five years, were nitric oxide (2007-2012), management (2019-2024), and impact (2019-2024), with the highest emergent strength being thermal injury. CONCLUSIONS Research on burn-related sepsis has shifted from focusing on early studies on pathogenesis and mortality to focus on prevention, treatment, and early diagnosis. Future research is expected to focus on early diagnosis and risk factors of burn-related sepsis.
Burns/complications* ; Sepsis/etiology* ; Humans ; Bibliometrics ; China

Objective:To build a big data analysis model of comprehensive performance of medical equipment,so as to improve the management efficiency and fine management level for medical equipment of hospital.Methods:The big data analysis model of comprehensive performances of medical equipment was developed through building a data integration platform,and integrating multi-business system data of hospital,and including quantified social benefit data and relative data of the process of procurement and maintenance,which established index system of performance analysis with multi-dimensions and multi-layers.It realized the presentation of evaluation results of performance of medical equipment in the form of visual data reports.Results:The big data analysis model for the comprehensive performance of medical equipment has set a system with more than 10 indicators,which included social-benefit indicators,evaluation indicators of comprehensive performance,income indicators,and the indicator of recovery period of investment,and visual report with 35 pages.Each layer of the performance of equipment was analyzed from 35 angles,which realized a comprehensive,multi-dimensional and refined evaluation for the performance of medical equipment of hospital.Its'agile,easy-to-use,efficient response and automation features can significantly improve work efficiency of business.The model realized automatic data collection through interfaces and other means,and reduced manual input errors,which data accuracy rate was＞99%.The results of testing the performance data of equipment for three consecutive years by using this model indicated that the consuming time of single calculation of business system of hospital was shortened from＞20 min to 5-8 s.Conclusion:The big data analysis model of comprehensive performance of medical equipment can help hospital to identify,prevent and control risks in advance,and improve the efficiency of internal control,and enhance management efficiency and fine management level for hospital,and provide support for management decision for medical equipment of hospital.

AIM:To investigate whether casein kinase 2(CK2)/calmodulin(CaM)/small-conductance Ca2+-activated K+channel type 2(SK2)signaling pathway mediates autophagy-induced sympathoexcitation in the paraventricu-lar nucleus(PVN)of rats with chronic heart failure(CHF).METHODS:We randomly divided 180 Wistar rats,aged 6 to 8 weeks,into 10 groups:sham+dimethyl sulfoxide(DMSO),sham+artificial cerebrospinal(aCSF),CHF+DMSO,CHF+aCSF,CHF+rapamycin(RAPA),CHF+3-methyladenine(3-MA),CHF+5,6-dichlorobenzimidazole riboside(DRB),CHF+calmidazolium chloride(CMDZ),CHF+N-cyclohexyl-N-[2-(3,5-dimethyl-1H-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine(CyPPA),and CHF+apamin groups.We measured cardiac function,hemodynamic parameters,anatomic indicators,and sympathetic drive indicators(n=18).Western blot was used to examine the protein levels of mi-crotubule-associated protein 1 light chain 3-II(LC3-II)/LC3-I,beclin-1,P62,CK2α,SK2,and phosphorylated CaM.The number of SK2-positive neurons was measured using immunofluorescence staining.The NG108 cells were randomly divided into 6 groups:DMSO,aCSF,RAPA,3-MA,RAPA+DRB,and RAPA+CMDZ groups.Radioisotope 32P-ATP pro-tein kinase activity assays were used to detect CK2 activity in cultured NG108 cells.We used Western blot to examine the protein levels of CK2α,SK2,and phosphorylated CaM.RESULTS:Compared with CHF rats treated with vehicle,CHF rats treated with RAPA or apamin exhibited increased sympathetic drive indicators,but decreased left ventricular ejection fraction and fractional shortening(P<0.01).However,CHF symptoms,including sympathoexcitation,were attenuated by 3-MA,DRB,CMDZ or CyPPA infusion into the PVN(P<0.01).In CHF rats,RAPA infusion into the PVN induced CK2 activity,up-regulated LC3-II/LC3-I,beclin-1,CK2α,and phosphorylated CaM levels,but down-regulated P62 and SK2 expression,as well as the number of SK2-positive neurons(P<0.05 or P<0.01).In CHF rats,infusion of 3-MA or DRB into the PVN decreased CK2 activity,and down-regulated phosphorylated CaM level(P<0.01).Infusion of 3-MA,DRB or CMDZ into the PVN up-regulated SK2 expression and the number of SK2-positive neurons(P<0.01).In cultured NG108 cells,RAPA induced CK2 activation and up-regulated the expression of CK2α and the phosphorylation of CaM,but down-regulated SK2 expression(P<0.01).Treatment with RAPA increased the level of phosphorylated CaM and down-regulated SK2 expression in cultured NG108 cells(P<0.01),which was inhibited by DRB and CMDZ(P<0.05 or P<0.01).CONCLUSION:In rats with CHF,the CK2/CaM/SK2 signaling pathway in the PVN contributes to autophagy-induced sympathoexcitation.

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.