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.

Hepatitis B virus （HBV） is a unique hepatotropic DNA virus that forms covalently closed circular DNA within the nucleus of hepatocytes and can partially integrate into the host genome， establishing the molecular basis for persistent viral infection. HBV infection and replication depends on multiple hepatocyte-enriched host factors and is modulated by the hepatic microenvironment. The host achieves natural control and clearance of HBV through various mechanisms， including cytolytic elimination mediated by cellular immunity such as cytotoxic T lymphocytes and natural killer cells， innate immunity and noncytolytic clearance driven by interferons and various cytokines， and antibody-mediated protection and clearance as part of humoral immune response. In addition， intracellular restriction factors and pathways， hepatocyte turnover through division and replacement， and changes in the hepatic microenvironment （such as the increase in matrix stiffness） collectively influence the efficiency and outcome of viral control and clearance. This article clarifies and elaborates on related mechanisms， so as to deepen the understanding of HBV chronicity， spontaneous resolution， and cure and provide a theoretical basis for optimizing clinical management and developing novel therapeutic strategies.

Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.

Objective This study aimed to examine whether body mass index(BMI)was causally associated with blood transfusion reactions.Methods A two-sample Mendelian randomization(MR)analysis using the inverse variance weighted(IVW),MR-Egger regression,weighted median method(WME),weighted model method(WM),simple model method(SM)and simple median method(SM)was performed.Public genome-wide association study(GWAS)analysis was used as the data source,with summary statistical data sets of BMI(n=126 003;GWAS ID:ebi-a-GCST90095042)as the exposure variable and summary statistical data sets of transfusion reactions(n=199 451;GWAS ID:finn-b-ST19)as the outcome variable.The causal association between BMI and transfusion reactions was analyzed.Results 42 single nucleotide polymorphisms associated with transfusion reactions were identified by MR analysis.The IVW showed evidence to support the causal relationship between BMI and transfusion reactions(OR=0.29,95%CI=0.10～0.85).Nonetheless,the effect value β of the MR-Egger regression approach contrasts with that of IVW.The outcomes of the heterogeneity analysis,pleiotropy analysis,and sensitivity analysis indicated that P>0.05.Conclusion The results of MR analysis supported the possibility of a causal relationship between BMI and blood transfusion reactions,that is,the reduction of BMI will increase the risk of blood transfusion reactions.

Objective To investigate the application of flipped classroom combined with teaching film-reading model in the teaching of filamentous fungal morphology for refresher doctors and evaluate its effect.Methods Fifteen refresher doctors taking microbiology from the 2022 batch of Guangdong Provincial People's Hospital were selected as the control group,and fifteen from the 2023 batch were se-lected as the experimental group.The"Morphological identification of Aspergillus and Mucor" was selected as the teaching content.The experimental group adopted flipped classroom combined with teaching film-reading model for teaching and the control group adopted tra-ditional teaching mode.The theoretical scores,operational scores,film-reading scores,and total scores of the two groups before and af-ter the implementation of teaching were compared and the teaching effect of the experimental group was evaluated using the Question-naire Star.Results The median scores of operational,film-reading,and total scores in the experimental group and control group were 40,30,and 95.5 and 36,27,and 85.5,respectively,and all the three scores in the experimental group were significantly higher than those in the control group(P＜0.05).Conclusion The flipped classroom combined with teaching film-reading model helps to improve the teaching effect of filamentous fungal morphology for refresher doctors,with high satisfaction,and can provide reference for subse-quent filamentous fungal morphology teaching.

AIM To study the chemical constituents from Dictamni Cortex.METHODS The 70％ethanol extract from Dictamni Cortex was isolated and purified by HP-20 macroporous resin,silica gel,MCI,ODS and preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.RESULTS Thirty-three compounds were isolated and identified as rutin(1),apigenin(2),catechin(3),hesperetin(4),leonuriside A(5),androsin(6),2-methoxy-4-acetylphenol-O-α-rhamnopyranosyl-(1"-6')-β-glucopyranoside(7),vanillic acid(8),gallic acid(9),4-hydroxybenzoic acid(10),benzoic acid(11),involcranoside B(12),benzyl β-D-glucopyranoside(13),bphenylethyl-rutinoside(14),1-bromonaphthalene(15),cimifugin(16),9(S),12(S),13(S)-trihydroxyoctadeca-10(E),15(Z)-dienoic acid(17),methyl-9,12,13-trihydroxyoctadeca-10,15-dienoate(18),7,8-dihydroxy-9,12(Z,Z)-octadecadienoic acid(19),vernolic acid(20),9,10(erythro)-dihydroxy-11 E-octadecadienoic acid methyl ester(21),(7Z,9E,13Z)-11-hydroxyhexadeca-7,9,13-trienoic acid(22),(7Z,10Z,14E,16Z,19Z)-13-hydroxydocosa-7,10,14,16,19-pentaenoic acid(23),(9E)-8,11,12-trihydroxyoctadecenoic acid methyl ester(24),n-hexanol-O-rutinoside(25),hexyl β-sophoroside(26),3-pentyl 6'-(3-hydroxy-3-methylglutaryl)-β-D-glucopyranoside(27),3-methylbut-3-enyl-6-O-β-D-glucopyranosyl-β-D-glucopyranoside(28),3-methyl-but-2-en-1-yl β-D-glucopyranoside(29),3-methylbutan-1-ol-β-D-glucopyranoside(30),pregnenolone(31),2-butoxytetrahydrofuran(32),psydrin(33).CONCLUSION Compounds 2-4,8-13,15-16,25-28 and 32-33 are isolated from Rutaceae family for the first time.

Objective:The genotoxicity risk of graphene artificial nerve sheath conduit was systematically evaluated to provide scientific evidence for their clinical safety and to establish methodological references for the genotoxicity assessment of nanomaterial medical devices.Methods:The potential effects of graphene artificial nerve sheath conduit on genetic and chromosomal endpoints were analyzed by integrating bacterial reverse mutation assays,in vitro chromosome aberration assays,mouse lymphoma cell TK gene mutation tests,and mammalian erythrocyte Pig-a gene mutation assays.Results:In the bacterial reverse mutation assay,all plates showed good background growth.There was no significant difference in the average number of revertant colonies between the test group and the negative control group,with a ratio around 1.0.In the in vitro chromosome aberration assay,the chromosomal aberration rate in the test group was less than 5％,showing no significant increase compared to the negative control group.In the mouse lymphoma cell TK gene mutation assay,the mutation frequency in the test group was less than twice that of the negative control group,with no significant difference.In the mammalian erythrocyte Pig-a gene mutation assay,the mutation frequencies of erythrocytes and reticulocytes in the test group were both less than 3× 10-6,showing no significant difference compared to the negative control group.Conclusions:Graphene artificial nerve sheath conduit exhibited no detectable genotoxicity under the tested conditions,the research results can provide reference and guidance for the genotoxicity evaluation of nanomaterial medical devices.

Objective To investigate the oral health status of second-grade primary school students in Suzhou,provide baseline data for evaluating Suzhou's"Bright Eyes and Healthy Teeth"public health project,and offer reference for formulating oral health policies for students in Suzhou.Methods A multi-stage,stratified,random sampling method was used to select 1 640 second-grade primary school students from 10 districts(county-level cities)across Suzhou.The oral health survey of primary school students in Suzhou was designedbased on WHO"Basic Methods for Oral Health Surveys"(5th edition).A survey on the students' oral health status was con-ducted.Results The caries prevalence,mean DMFT(Decayed,Missing,Filled Teeth),and caries filling rate for primary teeth among second-grade students in Suzhou were 80.73％,4.25,and 24.48％,respectively.For permanent teeth,the caries prevalence,mean DMFT(Decayed,Missing,Filled Teeth),and caries filling rate were 30.30％,0.62,and 16.96％,respectively.Specifically,the caries prevalence,mean DMFT,and filling rate for the first permanent molar were 29.88％,0.59,and 16.94％,respectively.The pit and fissure sealing rate for the first permanent molar was 13.74％.Additionally,the detection rate for gingival bleeding was 58.05％,and for dental calculus,49.15％.Conclusion The oral health status of second-grade primary school students in Suzhou is concerning.The caries prevalence rate for both primary and permanent teeth is high,while the filling rate is relatively low.Prior to the implementation of oral health programs,the pit and fissure sealing rate for the first permanent molars was low,with significant differ-ences observed between urban and rural areas,as well as among different districts(or county-level cities).

Objective:To explore the relationship between urinary cadmium levels and thyroid hormone levels in people aged 40-89 years old in selected areas of China.Methods:Based on the "Investigation of the Impact of Soil Quality of Agricultural Land on Human Health in Typical Areas" project from October 2019 to August 2020, a multi-stage stratified random sampling method was used to include 6 588 middle-aged and older adults aged 40-89. Demographic characteristics, dietary frequency and disease status were collected through the questionnaire and physical examination. Urinary cadmium and urinary creatinine were detected by random midstream urine. Fasting venous blood was collected for the detection of Triiodothyronine (T3) and Thyroxine (T4). The linear mixed effects model was used to explore the association of urine cadmium levels with thyroid hormone levels. Its dose-response relationship was explored by using the restricted cubic spline.Results:The age of the subjects was (63.48±12.18) years, with males accounting for 51.28%. The M ( Q 1,Q 3) of urinary cadmium level, T3 and T4 was 2.48 (1.36, 4.42) μg/g·creatinine, (1.96±0.51) nmol/L and (113.75±29.11) nmol/L, respectively. The linear mixed effects model showed that the changes of T3 and T4 were 0.027 (0.009, 0.044) nmol/L and 2.019 (1.084, 2.953) nmol/L for each one-unit increase (natural logarithm transformed) of urinary cadmium. The restricted cubic spline showed that there was a positive nonlinear association between urinary cadmium and T3 as well as T4 (all Pnonlinear<0.05). Conclusion:In selected areas of China, the urinary cadmium level of middle-aged and older adults aged 40-89 years is positively associated with T3 and T4.

Objective This study aimed to examine whether body mass index(BMI)was causally associated with blood transfusion reactions.Methods A two-sample Mendelian randomization(MR)analysis using the inverse variance weighted(IVW),MR-Egger regression,weighted median method(WME),weighted model method(WM),simple model method(SM)and simple median method(SM)was performed.Public genome-wide association study(GWAS)analysis was used as the data source,with summary statistical data sets of BMI(n=126 003;GWAS ID:ebi-a-GCST90095042)as the exposure variable and summary statistical data sets of transfusion reactions(n=199 451;GWAS ID:finn-b-ST19)as the outcome variable.The causal association between BMI and transfusion reactions was analyzed.Results 42 single nucleotide polymorphisms associated with transfusion reactions were identified by MR analysis.The IVW showed evidence to support the causal relationship between BMI and transfusion reactions(OR=0.29,95%CI=0.10～0.85).Nonetheless,the effect value β of the MR-Egger regression approach contrasts with that of IVW.The outcomes of the heterogeneity analysis,pleiotropy analysis,and sensitivity analysis indicated that P>0.05.Conclusion The results of MR analysis supported the possibility of a causal relationship between BMI and blood transfusion reactions,that is,the reduction of BMI will increase the risk of blood transfusion reactions.