Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

Background: The tight junction protein claudin18.2 (CLDN18.2) has been implicated in poor prognosis and suboptimal immunotherapy response in gastric cancer (GC). This study investigates the clinicopathological relevance of CLDN18.2 expression and its association with molecular subtypes in GC patients from a high-incidence region, combining transcriptomic and proteomic approaches to explore how CLDN18.2 contributes to progression and metastasis. Methods: A retrospective cohort of 494 GC patients (2019–2024) underwent immunohistochemical analysis for CLDN18.2, Epstein-Barr virus (Epstein–Barr virus–encoded RNA), p53, human epidermal growth factor receptor 2 (HER2), and mismatch repair proteins (MLH1, MSH2, PMS2, and MSH6). CLDN18.2 positivity was defined as moderate to strong (2+/3+) membranous staining in ≥75% of tumor cells. Clinicopathological correlations, biomarker associations, and survival outcomes were evaluated. Transcriptomic and proteomic sequencing was performed to explore molecular mechanisms. Results: CLDN18.2 positivity was observed in 26.9% (133/494) of gastric adenocarcinomas. CLDN18.2-positive tumors correlated with TNM stage (p = .003) and shorter overall survival (p = .018). No associations were identified with age, sex, HER2 status, microsatellite instability, or Epstein-Barr virus infection. Transcriptomic profiling revealed CLDN18.2-high tumors enriched in pathways involving cell junction disruption, signaling regulation, and immune modulation. Proteomic profiling showed that tumors with high CLDN18.2 were enriched in multiple mechanism-related pathways such as integrated metabolic reprogramming, cytoskeletal recombination, immune microenvironment dysregulation, and pro-survival signaling. These mechanisms may collectively contribute to tumor progression and metastasis. Conclusions CLDN18.2 overexpression is associated with poor prognosis in GC patients. Transcriptomic and proteomic analyses demonstrate that CLDN18.2 promotes tumor progression and metastasis, underscoring its potential as an independent prognostic factor in regions with a high incidence of GC.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

Anticoagulants are widely used in the prevention and treatment of thromboembolism.Existing anticoagulants share the common feature of antagonizing or blocking critical steps in the coagulation cascade,which also increases the risk of bleeding.Studies have indicated that factor Ⅺ inhibitors represent a potential therapeutic option for balancing thrombosis and bleeding risks.In recent years,various factor Ⅺ inhibitors,including antisense oligonucleotides(ASOs),monoclonal antibodies,synthetic small molecules,natural peptides,and aptamers,have been extensively researched as potentially exploitable anticoagu-lants.Research findings also suggest that factor Ⅺ inhibitors can reduce bleeding risks while ensuring anticoagulant efficacy,ex-hibiting potential for thrombosis prevention and treatment in patient populations such as those with end-stage renal disease,non-cardioembolic ischemic stroke,and acute coronary syndrome.This article reviewed the mechanisms of action,drug classes,pharma-cological characteristics,and clinical research progress of factor Ⅺ inhibitors,aiming to provide insights into the development of new anticoagulants and clinical anticoagulant therapies.

Objective To investigate the establishment and evaluation of an idiopathic pulmonary fibrosis(IPF)mouse model induced by the intratracheal infusion of bleomycin(BLM)of different concentrations.Methods Male C57BL/6J mice were randomly divided into a control group,Model-L group(1.5 mg/kg,BLM),Model-M group(2.5 mg/kg,BLM),and Model-H group(3.5 mg/kg,BLM).An IPF mouse model was constructed by one-time intratracheal infusion of BLM.The general status,body mass,survival rate,and lung coefficient of mice in different groups were compared.Pathological changes in lung tissue,the hydroxyproline content,fibrosis markers and inflammatory factor levels were observed.Results Compared with the control group,the survival rate decreased and body weight showed a downward trend in the low-,medium-,and high-dose model groups,with significant increases in lung coefficients.Inflammatory infiltration(P＜0.01)and collagen deposition(P＜0.0001)were observed in the lung tissues of all model groups.Hydroxyproline levels in lung tissue and serum were significantly elevated(P＜0.05).The mRNA levels of fibrosis markers α-Sma,Fn1,and Col1a1 were upregulated(P＜0.001),with significant increases in corresponding protein expression(P＜0.05).The mRNA expression of the inflammatory factor Tgfb1 also increased(P＜0.0001).Conclusion 1.5,2.5 and 3.5 mg/kg BLM can induce an IPF model in C57BL/6J mice.Based on the results observed for survival rate,body mass,lung coefficient changes,lung tissue gross and pathological changes,and fibrosis-related biomarkers,2.5 mg/kg BLM is the optimal concentration for inducing an IPF mouse model.

BACKGROUND:Previous studies have demonstrated that moxibustion can alleviate osteoarthritis-induced cartilage lesions and delay the progression of knee osteoarthritis. In a previous study conducted by our research group,it was found that regulating the circPan3/miR-667-5p/Ghrelin signaling pathway can enhance the level of autophagy in chondrocytes,thereby exerting a cartilage protective role in knee osteoarthritis. OBJECTIVE:To explore the effect of moxibustion on knee osteoarthritis cartilage in rats based on the circPan3/miR-667-5p/Ghrelin signaling pathway. METHODS:Sprague-Dawley rats were randomly divided into three groups (n=10 per group):sham operation,model,and moxibustion groups. A rat model of knee osteoarthritis was established in the latter two groups by anterior cruciate ligament transection and medial meniscus resection. Rats in the sham operation group underwent arthrotomy only. At 6 weeks after modeling,moxibustion intervention at Zusanli and Shenyu acupoints was applied in the moxibustion group,20 minutes daily for 4 weeks,while the other two groups did not receive any special treatment. After 4 weeks,histopathological staining was performed to observe the degree of synovial lesions and cartilage damage in the knee joint. Additionally,changes in the serum levels of inflammatory cytokines,interleukin-6 and tumor necrosis factor-α,were detected by enzyme-linked immunosorbent assay. Furthermore,chondrocytes isolated from the above three groups of rats were divided into three groups:a normal control group,a model group,and a moxibustion group. The expression levels of cartilage matrix anabolic molecules (type Ⅱ collagen and Sox9),matrix degradation molecules (matrix metalloproteinase 13 and ADAMTS5),autophagy markers (ATG5,Beclin-1,microtubule-associated protein 1 light chain 3),Ghrelin,CircPan3,and miR-667-5P were determined by western blot and qRT-PCR in each group. RESULTS AND CONCLUSION:After 4 weeks of treatment,the model group exhibited significant thickening of the synovium,infiltration of inflammatory cells,narrowing of the joint space,rough and uneven cartilage surfaces,thinning,reduction in the number of chondrocytes,a significant increase in synovitis and Osteoarthritis Research Society International scores,and a significant up-regulation of interleukin-6 and tumor necrosis factor-α levels (P<0.0001). In comparison,the sham operation group showed no significant changes. Compared with the model group,the moxibustion group exhibited a reduction in synovial thickening,a decrease in inflammatory cell infiltration,an increase in joint space,a reduction in cartilage roughness and loss of integrity,an increase in the number of chondrocytes,a reduction in synovitis and Osteoarthritis Research Society International scores,and a significant reduction in the levels of interleukin-6 and tumor necrosis factor-α (P<0.0001). The results of in vitro experiments demonstrated that the expression of matrix metalloproteinase 13,ADAMTS5,and miR-667-5P was elevated,while the expression of type Ⅱ collagen,Sox9,autophagy markers,Ghrelin,and Circpan3 was reduced in the model group compared with the normal control group (P<0.01). Moxibustion was found to reverse these changes in the moxibustion group compared with the model group (P<0.01). To conclude,moxibustion may enhance chondrocyte autophagy by modulating the circPan3/miR-667-5p/Ghrelin signaling pathway,which may inhibit knee osteoarthritis inflammation and cartilage destruction,exerting a protective effect on cartilage.

In 2024,the Japanese Circulation Society(JCS)and the Japanese Heart Rhythm Society(JHRS)jointly released the updated guidelines for the management of cardiac arrhythmias.The guideline provided updates on strategies for arrhythmias management,including device therapy,catheter ablation,pharmacological treatment and comprehensive management of atrial fibrillation(AF).This article focuses on the management of AF,including stroke risk assessment,oral anticoagulation therapy,high-risk patients management,comprehensive strategies,and lifestyle interventions.The guideline proposed a new stroke risk scoring tool,the HELT-E2 S2 score,refined the management of anticoagulation therapy in special high-risk patients,and updated comprehensive management strategies and lifestyle interventions for AF.These updates aim to enhance the prognosis and quality of life for AF patients,and also provide valuable insights for the management optimization of AF patients in China.