Chronic obstructive pulmonary disease （COPD） is a chronic respiratory disease that poses a significant threat to global health， exhibiting high morbidity， disability and mortality rate， with its prevention and treatment situation becoming increasingly critical. The pathogenesis of COPD is complex， and the underlying cellular and molecular biological mechanisms remain incompletely elucidated. Programmed cell death （PCD） is the process wherein cells actively undergo demise to maintain internal environmental stability in response to certain signals or specific stimuli. Contemporary medical research indicates that the dysregulation of PCD patterns such as apoptosis， necroptosis， pyroptosis， autophagy， and ferroptosis is closely related to the onset and progression of COPD. Clarifying the molecular mechanisms of PCD in COPD may provide novel perspectives for in-depth understanding and prevention of the disease. Traditional Chinese medicine （TCM） is characterized by holistic regulation. In recent years， extensive research has been conducted in the TCM field focusing on modulating apoptosis， necroptosis， pyroptosis， autophagy， and ferroptosis for the treatment of COPD， yielding remarkable achievements. Therefore， this study systematically explored the molecular mechanism of PCD in COPD and reviewed the potential mechanisms and intervention status of TCM targeting PCD in COPD， aiming to provide insights and references for the clinical prevention， treatment and in-depth research of COPD.

Chronic obstructive pulmonary disease （COPD） is a chronic respiratory disease that poses a significant threat to global health， exhibiting high morbidity， disability and mortality rate， with its prevention and treatment situation becoming increasingly critical. The pathogenesis of COPD is complex， and the underlying cellular and molecular biological mechanisms remain incompletely elucidated. Programmed cell death （PCD） is the process wherein cells actively undergo demise to maintain internal environmental stability in response to certain signals or specific stimuli. Contemporary medical research indicates that the dysregulation of PCD patterns such as apoptosis， necroptosis， pyroptosis， autophagy， and ferroptosis is closely related to the onset and progression of COPD. Clarifying the molecular mechanisms of PCD in COPD may provide novel perspectives for in-depth understanding and prevention of the disease. Traditional Chinese medicine （TCM） is characterized by holistic regulation. In recent years， extensive research has been conducted in the TCM field focusing on modulating apoptosis， necroptosis， pyroptosis， autophagy， and ferroptosis for the treatment of COPD， yielding remarkable achievements. Therefore， this study systematically explored the molecular mechanism of PCD in COPD and reviewed the potential mechanisms and intervention status of TCM targeting PCD in COPD， aiming to provide insights and references for the clinical prevention， treatment and in-depth research of COPD.

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.

Objective: To investigate the factors influencing the co-prevalence of allergic rhinitis and obesity among primary and secondary school students in Inner Mongolia, so as to provide a data foundation and theoretical basis for developing targeted intervention measures. Methods: In September and October 2024, a stratified cluster random sampling method was employed to select 139 102 students from 539 schools across 12 leagues/cities and 103 banners/counties in Inner Mongolia Autonomous Region. Participants who were diagnosed with allergic rhinitis by a doctor at least once within one year and had a body mass index ≥ 28 kg/m 2 were considered to have comorbid conditions. Results: The coprevalence rate of allergic rhinitis and obesity among primary and secondary school students in Inner Mongolia was 6.4% (8 931 cases). Lasso-Logistic regression revealed that nonboarding status, higher maternal education, consuming high protein foods ≥1 time daily, occasionally or never eating breakfast, engaging in moderate to vigorous physical activity for ≥60 minutes on fewer than half of holidays, and having been exposed to second hand smoke in person within the past seven days were associated with higher odds ratios for co-prevalence of allergic rhinitis and obesity( OR = 1.23 , 1.22-1.63, 1.20, 1.19, 1.38, 1.35); being female, higher grade level, residence in flag/county/district areas, non only child status, never having consumed a full glass of alcohol, non hypertensive status, and households without pets were associated with lower co-prevalence risks ( OR =0.65, 0.67-0.77, 0.81, 0.87, 0.73, 0.41, 0.68) (all P <0.05). The ROC curve indicated an area under the curve of 0.64 for the predictive model, demonstrating satisfactory discriminatory ability. The calibration curve showed consistency between predicted and actual occurrence probabilities. Conclusions The co-prevalence of allergic rhinitis and obesity among primary and secondary school students in Inner Mongolia is closely associated with demographic characteristics, dietary behaviours, and lifestyle habits. Future prevention and control strategies should prioritize these factors to implement targeted interventions.

ObjectiveTo investigate the effects of jatrorrhizine on endogenous metabolites and metabolic pathways in the mouse model of ulcerative colitis. MethodsThirty male C57BL/6J mice were randomly divided into the normal group， the model group， the low-dose and high-dose jatrorrhizine groups （0.04， 0.16 g·kg^-1）， and the mesalazine group （0.52 g·kg^-1）The mouse model of ulcerative colitis was established with 3% dextran sulfate sodium （DSS） and treated with different doses of jatrorrhizine by gavage. The changes in body weight， colon length， disease activity index （DAI）， and colonic histopathology were analyzed to evaluate the therapeutic effects of jatrorrhizine. UPLC-Q-TOF/MS was employed to determine the serum and fecal levels of metabolites in mice. Metabolomics methods were used to screen the differential metabolites， on the basis of which the potential therapeutic mechanism of jatrorrhizine on DSS-induced ulcerative colitis in mice was investigated. ResultsAfter intervention with jatrorrhizine， the model mice showed significantly decreased DAI（P<0.05，P<0.01）， recovered colon length，（P<0.05，P<0.01） and alleviated histopathology of the colon. The metabolomics study screened out 13 differential metabolites in the serum and 8 differential metabolites in the feces. The pathway enrichment analysis predicted three potential metabolic pathways： Biosynthesis of unsaturated fatty acids， phenylalanine， tyrosine and tryptophan biosynthesis， and phenylalanine metabolism. ConclusionJatrorrhizine may treat ulcerative colitis by regulating the biosynthesis and metabolism of amino acids and the synthesis of unsaturated fatty acids.

Background: High coal dust exposure threatens miners’ occupational health and safety. While dust control is mainly implemented by enterprises, miners’ active participation is crucial for effective collaborative prevention. This study develops a feature reduction, genetic algorithm, and backpropagation (RS-GA-BP) hybrid evaluation model integrating behavioral and psychosocial factors to quantitatively assess collaborative dust prevention performance in coal mines. Methods: Guided by the theory of collaborative dust prevention among coal miners, this study incorporated human factors into the evaluation framework of prevention effectiveness. Using the rough set method, five key influencing factors were identified from twelve candidate variables. A prediction model for collaborative dust prevention effectiveness (RS-GA-BP) was then developed and applied by optimizing the BP neural network with a genetic algorithm. Results: The results indicated that technical context, conformity tendency, group cohesion, group driving force, and group dissipative force were the principal factors influencing collaborative prevention outcomes. Based on 955 survey responses from front-line coal miners, the model was trained and validated. The results showed that the GA-BP model outperformed the traditional BP model in terms of root mean square error, mean absolute error, and mean absolute percentage error, achieving a prediction accuracy of 95.73%. Conclusion The research results indicate that the RS-GA-BP model can effectively evaluate the dust prevention and control effectiveness among coal miners, thereby enriching the methodological framework for assessing dust prevention effectiveness in coal mines.

Objective To evaluate the left ventricular systolic function of patients with type 2 diabetes mellitus(T2DM)combined with renal insufficiency(CKD)by applying automated myocardial motion quantifica-tion(aCMQ)and to investigate its correlation with clinical biochemical indexes.Methods 80 patients with T2DM were enrolled,divided into DM group(without CKD,n=40)and DN group(with CKD,n=40),and 40 healthy volunteers were selected as the control group.The general clinical data of all subjects were recorded,and routine echocardiography and aCMQ were performed to obtain routine ultrasonographic measurements and aCMQ-related parameters.Results Comparison of aCMQ-related parameters:The differences in LV global longitudinal strain(LVGLS),LV apical 2-chamber longitudinal strain(LVAP2LS),LV apical 3-chamber longitudinal strain(LVAP3LS),and LV apical 4-chamber longitudinal strain(LVAP4LS)among the three groups were all statistically significant(P<0.05).The differences in LV global circumferential strain(LVGCS)between the DN group and the other two groups were statistically significant(P<0.05).The differences in LV short-axis basal segment cyclic strain(LVSAXBCS),LV short-axis middle segment cyclic strain(LVSAXMCS),and LV short-axis apical segment cyclic strain(LVSAXACS)were not statistically significant(P>0.05).LV strain was negatively correlated with Hs-CRP,GA,HbA1c,creatinine,urea,and uric acid,and positively correlated with eGFR.Correlation.High-sensitivity C-reactive protein(Hs-CRP),glycated albumin(GA)and eGFR showed good correlation with LV strain parameters.Conclusion The aCMQ technique can detect the deterioration of left ventricular function in patients with type 2 diabetes mellitus combined with renal insufficiency at an early stage,and the correlation between left ventricular strain parameters and hs-CRP,GA and eGFR can help to better assess their cardiac involvement.

Objective To detect the adverse drug reaction(ADR)signals of tetracycline representative drugs(tetracy-cline,minocycline,tigecycline,and doxycycline)in children,and to provide reference for safe clinical medication.Methods A total of 34 quarters of ADE report data related to four tetracyclines from the first quarter of 2015 to the second quarter of 2023 in the US FDA Adverse Event Reporting System(FAERS)were collected and grouped according to the age of minor children.The re-port odds ratio(ROR)method and the comprehensive standard method(MHRA)were used for signal mining.Results A to-tal of 367 461 reports were retrieved from the FAERS database for all minor children under 18 years old.There were 43,583,40 and 501 reports related to tetracycline,minocycline,tigecycline and doxycycline,respectively.A total of 280 ADE signals were de-tected after deduplication,involving 22 system organ classifications.Tetracycline was concentrated in the gastrointestinal system and various nervous systems.Minocycline was mainly in the hepatobiliary system,endocrine system,and subcutaneous and subcu-taneous tissue diseases.Tigecycline was involved in the gastrointestinal system,systemic diseases and various reactive diseases at the administration site,Doxycycline was concentrated in the gastrointestinal system,mental illness,skin and subcutaneous tissue diseases.And it was found that psychosis was not involved in adverse reactions.Adverse reactions not included in the instructions include blindness and papilledema caused by minocycline,hypertriglyceridemia and acute pancreatitis caused by tigecycline,Bell's palsy,growth retardation,blindness,depression,suicidal thoughts and anxiety caused by doxycycline.Conclusions In different age groups of minor children,there are some differences in ADR among the four tetracycline drugs.ADR should be strictly monitored when using tetracycline drugs in all children.While paying attention to the effects of these drugs on children's teeth and bones,other ADE should also be vigilant,such as Jarisch-Herxheimer reaction,acne,thyroiditis,headache.The newly discovered involvement of systemic organs and AE can provide a reference for improving the adverse reactions of tetracycline-representative drugs to ensure the treatment safety of patients.

Large inter-individual and intra-individual differences in the expression and activity of drug-metabolizing enzymes(DMEs)contribute to unpredictable drug response and toxicity,which is a challenge facing precision medicine.Nuclear receptor-mediated transcriptional regulation and epigenetic mechanisms including histone modifications,non-coding RNAs,and DNA methylation can help to explain the individual variability in DME expressions.However,several questions remain unanswered.Recently,epitranscriptomics,an emerging field,provides new insights into the regulation of gene expression.As the most abundant RNA modification in eukaryotes,N6-methyladenosine(m6A)modifi-cation plays key roles in various physiological and pathological processes.This review summarizes the recent progress in m6A modification-mediated individual variability in DME expression in terms of the role of m6A modification in regulating basal expression of DMEs,crosstalk between m6A modification and nuclear receptors during the ontogeny of DMEs,and the contribution of m6A modification to xenobi-otic exposure-mediated changes in DME expression.This review aims to provide data for the elucida-tion of individual variations in drug metabolism in clinic.

Aim To investigates whether sphingosine-1-phosphate(S1P)regulates the expression of mitochon-drial calcium uniporter(MCU)via the sphingosine-1-phosphate receptor/proline-rich tyrosine kinase 2(S1PR/Pyk2)sig-naling pathway,thereby reducing oxidative stress-induced mitochondrial damage and inhibiting mitochondria-related apopto-sis.Methods Human umbilical vein endothelial cells(HUVEC)were subjected to oxidative damage using hydrogen peroxide(H2O2)as a model.Different concentrations of S1P were applied to the oxidative damaged HUVEC.Addi-tionally,the S1PR1 agonist SEW2871,the S1PR1 inhibitor W146,and the Pyk2 inhibitor PF-562271 were used to explore the specific mechanism of S1P action.Results S1P treatment significantly alleviated oxidative damage in HUVEC and was accompanied by an increase in S1PR1 expression(P<0.05),while S1PR3 expression remained unchanged.Mean-while,the expression levels of Pyk2 and MCU decreased(P<0.05).SEW2871 further reduced mitochondrial damage,whereas W146 exacerbated it(P<0.05).Furthermore,the application of the Pyk2 inhibitor PF-562271 also reduced H2O2-induced mitochondrial damage(P<0.05),further confirming the role of Pyk2 in this process.Conclusion S1P reduces H2O2-induced mitochondrial damage and inhibits mitochondria-related apoptosis in HUVEC by suppressing Pyk2 expression via S1PR1.