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.

Objective To develop a predictive model for postoperative pulmonary complications (PPC) following video-assisted thoracic surgery (VATS) in lung cancer patients by integrating cardiopulmonary exercise testing (CPET) parameters and machine learning techniques. Methods A retrospective analysis was conducted on patients with early-stage non-small cell lung cancer who underwent CPET and VATS at Guangdong Provincial People’s Hospital between October 2021 and July 2023. Patients were divided into a PPC group and a non-PPC group. The least absolute shrinkage and selection operator (LASSO) regression was used to select important features associated with PPC. Six machine learning algorithms were utilized to construct prediction models, including logistic regression, support vector machine, k-nearest neighbors, random forest, gradient boosting machine, and extreme gradient boosting. The optimal model was interpreted using SHapley Additive exPlanations (SHAP). Results A total of 325 patients were included, with an average age of 60.36 years, and 55.1% were male. Significant differences were observed between the PPC and non-PPC groups in age, diabetes, coronary heart disease, surgical approach, forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FVC% predicted, peak oxygen uptake (peak VO2), anaerobic threshold (AT), and ventilatory equivalent for carbon dioxide slope (VE/VCO2 slope) (P<0.05). In the predictive model constructed by selecting 7 key features using LASSO regression, the random forest model demonstrated the best overall performance across various metrics, with an area under the receiver operating curve of 0.930, an F1 score of 0.836, and a Brier score of 0.133 in the training set. It also exhibited good predictive ability and calibration in the test set. SHAP analysis ranked feature importance as follows: peak VO2, VE/VCO2 slope, age, FEV1, smoking history, diabetes, and surgical approach. Conclusion Integrating CPET parameters, the random forest model can effectively identify high-risk patients for PPC and has the potential for clinical application.

Background Prenatal exposure to fine particulate matter (PM_2.5) is closely associated with cortical damage and neuroinflammation in offspring. The cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS)–stimulator of interferon genes (STING) signaling pathway is a key regulator of inflammation and may be subject to epigenetic regulation. Objective To investigate the role of cGAS-STING pathway activation in PM_2.5-induced cortical damage in offspring mice during pregnancy and the underlying epigenetic regulatory mechanisms. Methods Open field tests were used to assess depressive-like behavior in offspring mice. Morphological analysis was conducted to evaluate cortical damage and microglial activation in offspring brains. Real-time fluorescent quantitative PCR (RT-qPCR) and Western blot (WB) were performed to detect changes in the expression of key molecules in the cGAS-STING pathway in cortical tissue. A PM_2.5-induced microglial cell injury model was established in BV2 cells. Microglial activation was observed, cell viability was measured using the Cell Counting Kit-8 (CCK-8), and the expression levels of inducible nitric oxide synthase (iNOS) and key molecules in the cGAS-STING pathway were detected by RT-qPCR and WB. Bioinformatics analysis was performed to explore the epigenetic regulatory association between the STING signaling pathway and lysine-specific demethylase 5A (KDM5A). Changes in KDM5A mRNA and protein expression, as well as the protein level of histone H3 lysine 4 trimethylation (H3K4me3), were detected in an in vitro PM_2.5 injury model. Using small interfering RNA (siRNA) technology, the KDM5A gene was silenced in BV2 cells exposed to PM_2.5. The protein expression of H3K4me3 was detected to evaluate improvements in microglial activation, changes in inflammatory markers such as iNOS and mannose receptor (CD206), and alterations in the cGAS-STING pathway. Results Compared with the control group, the total distance of offspring mice in the PM_2.5 group was significantly reduced, and both the distance traveled and the time spent in the central area of the open field were significantly decreased (P<0.01, P<0.001), indicating depressive-like behavior in the offspring mice. Compared with the control group, the offspring mice in the PM_2.5 group exhibited disorganized cortical structure and significantly activated microglia (P<0.01), with significantly increased mRNA and protein levels of cGAS and STING (P<0.05, P<0.01, or P<0.001). The in vitro experiments demonstrated that the PM_2.5 treatment induced BV2 cells to polarize toward the M1 phenotype, exhibiting a distinct amoeboid morphology, with upregulated expression of the pro-inflammatory factor iNOS (P<0.05, P<0.01, or P<0.001) and activation of the cGAS-STING pathway (P<0.05, P<0.01). The analysis of RNA-seq data from KDM5A knockout cells revealed significantly downregulated STING expression, suggesting that KDM5A may activate the STING signaling pathway. The in vitro experiments further confirmed that the PM_2.5-treated BV2 cells exhibited significantly elevated mRNA and protein levels of KDM5A (P<0.01), while the H3K4me3 protein levels were markedly reduced (P<0.05). After silencing KDM5A in BV2 cells exposed to PM_2.5, compared with the PM_2.5+siNC group, the PM_2.5+siKDM5A group showed no obvious microglial activation and polarized toward the M2 phenotype, with significantly decreased expression levels of iNOS, cluster of differentiation 16 (CD16), and interleukin-1β (P<0.05, P<0.01), and significantly increased expression levels of anti-inflammatory factors CD206, YM1, and interleukin-10 (P<0.01, P<0.001). Meanwhile, the expression levels of cGAS and STING were also reduced (P<0.05, P<0.01). Conclusion KDM5A activates microglia through the cGAS-STING pathway, thereby contributing to PM_2.5-induced cortical damage in offspring mice during pregnancy.

Objective To investigate the association between butyrate metabolism-related genes(BMRGs)and the prognosis of lung adenocarcinoma(LUAD),construct a prognostic model,and evaluate its predictive value.Methods Differentially expressed BMRGs(BMR-DEGs)were screened from the TCGA-LUAD dataset.Cox and LASSO regression analyses were employed to establish a risk scoring model,stratifying patients into low-and high-risk groups.The model's performance was assessed using Kaplan-Meier(K-M)and receiver operating characteristic(ROC)curves,with external validation conducted using the GSE68465 dataset.In vitro experiments included RT-PCR and Western blotting to measure insulin-like growth factor binding protein 1(IGFBP1)expression.IGFBP1 was knocked down using siRNA,and its effects on cell proliferation,migration,and invasion were evaluated via CCK-8,colony formation,Transwell,and wound healing assays.Gene Set Enrichment Analysis(GSEA)was performed to explore IGFBP1-related regulatory mechanisms.Results We identified a total of 51 BMR-DEGs,primarily involved in biological processes such as cell proliferation,migration,and invasion,and associated with the PI3K-Akt and MAPK signaling pathways.The constructed 5-gene risk scoring model demonstrated that high-risk patients had significantly worse overall survival(OS)than low-risk patients(P＜0.05).IGFBP1 was highly expressed in LUAD tissues and correlated with poor prognosis.Knockdown of IGFBP1 significantly suppressed cancer cell proliferation,migration,and invasion(P＜0.05).GSEA revealed that IGFBP1 was linked to lipid metabolism-related pathways.Conclusion BMRGs are associated with LUAD prognosis,and the established risk scoring model exhibits strong predictive performance.High IGFBP1 expression correlates with unfavorable outcomes,and its knockdown inhibits cancer cell proliferation,migration,and invasion.

The purpose of this study was to investigate the effect of medium-chain fatty acids(MC-FAs)caprylic acid(C8∶0)on lipid metabolism of calf hepatocytes.Primary calf hepatocytes were extracted and cultured,and 1.2 mmol/L nonesterified fatty acids(NEFAs)were added to the hep-atocytes to construct a model of hepatic lipid deposition in primary calf hepatocytes,Five process-ing groups have been set up:Control group(Ctrl),NEFA added group(NEFA),C8∶0 1.2 mmol/L treatment group(C8∶0 1.2),NEFA+C8∶0 0.2 mmol/L treatment group(NEFA+C8∶00.2),C8∶0 0.2 mmol/L treatment group(C8∶0 0.2).Stimulate calf liver cells for 12 hours,and the levels of triglyceride(TG),lipid oxidation(MDA),hydrogen peroxide(H2O2)and total SOD activity were detected by biochemical kit,and FAS,a protein related to lipid synthesis,was detec-ted by Western blot.The results showed that compared with the control group,the concentrations of TG,MDA and H2O2 in NEFA group increased significantly(P＜0.01),and the activity of SOD decreased significantly(P＜0.05).The protein expression levels of FAS,ACC1,DGAT2 and SREBP-1C were significantly up-regulated(P＜0.01),while the expression level of CPT1A was significantly down-regulated(P＜0.01).Compared with the NEFA group,the protein expression levels of SREBP-1C and DGAT2 in the NEFA+C8∶0(concentration 0.2 mmol/L)group de-creased significantly(P＜0.05),and the protein expression level of fatty acid β-oxidation related molecule CPT1A was slightly higher than that in the NEFA group,but there was no statistical sig-nificance(P＞0.05),and the MDA level in hepatocytes decreased significantly(P＜0.05).In a word,the results of this study show that C8∶0 has antioxidant effect,which can effectively reduce the liver injury caused by oxidative stress,regulate the expression of liver fat gene,and then pro-tect liver injury.

Objective To investigate the relationship of C-reactive protein-albumin-lymphocyte(CALLY)index,serum autotaxin and serine protease 2(PRSS2)with postoperative recurrence and metastasis in gastric cancer patients.Methods A total of 188 patients who underwent radical gastrectomy for gastric cancer from December 2019 to December 2021 were selected as the research subjects.According to the postoperative situation,they were divided into the recurrence and metastasis group(n=72)and the non-recurrence and metastasis group(n=116).C reactive protein(CRP)was detected by immunoturbidimetry,albumin was detected by bromocresol green method,lymphocyte count was detected by blood routine analyzer,and CALLY index was calculated.Enzyme-linked immunosorbent assay was used to detect serum levels of autotaxin and PRSS2,and Spearman/Pearson correlation analysis was used to analyze the correlation between CALLY index,serum autotaxin,PRSS2 levels and clinical data.Multivariate logistic regression was used to analyze the influencing factors of recurrence and metastasis in patients with gastric cancer after radical resection,and receiver operating characteristic(ROC)curve was used to analyze the predictive value of CALLY index,serum autotaxin and PRSS2 levels for recurrence and metastasis in patients with gastric cancer after radical resection.Kaplan-Meier method was used to analyze the relationship between CALLY index,serum autotaxin,PRSS2 levels and postoperative recurrence and metastasis.Results Compared with the non-recurrence and metastasis group,the recurrence and metastasis group had a higher proportion of patients with TNM stage Ⅲ,Borrmann type Ⅲ-Ⅳ,lymphovascular invasion,neoadjuvant therapy and postoperative chemotherapy,higher serum levels of autotaxin and PRSS2,and lower CALLY index(P<0.01).TNM stage,Borrmann type,lymphovascular invasion,neoadjuvant therapy and postoperative chemotherapy were negatively correlated with CALLY index,and positively correlated with serum autotaxin and PRSS2 levels,while serum autotaxin and PRSS2 levels were negatively correlated with CALLY index(P<0.01).TNM stage,Borrmann type,lymphovascular invasion,CALLY index,autotaxin and PRSS2 were the influencing factors of recurrence and metastasis in patients with gastric cancer after radical resection(P<0.05,P<0.01).The area under the curve(AUC)of CALLY index,autotaxin and PRSS2 for predicting recurrence and metastasis was 0.962,which was significantly larger than that of CALLY index,autotaxin and PRSS alone(P<0.01).The 3-year recurrence and metastasis rate of patients with low CALLY index expression[56.52%(52/92)]was higher than that of patients with high CALLY index expression[20.83%(20/96)](P<0.01).The 3-year recurrence and metastasis rate of patients with high expression of autotaxin[49.47%(47/95)]was higher than that of patients with low expression[26.88%(25/93)](P<0.01).The 3-year recurrence and metastasis rate of patients with high PRSS2 expression[47.87%(45/94)]was higher than that of patients with low PRSS2 expression[28.72%(27/94)](P<0.01).Conclusion The CALLY index decreases,and serum autotaxin and PRSS2 increase in patients with postoperative recurrence and metastasis of gastric cancer.The combined prediction of the three factors demonstrates higher predictive performance for postoperative recurrence and metastasis.

Objective:To investigate the relationship between dynamic alterations in serum albumin (ALB) concentrations and clinical outcomes in hospitalized surgical patients, thus providing a basis for optimizing clinical management strategies.Methods:This study utilized data from a prospective observational cohort study on nutritional status among 7 122 elderly hospitalized patients across 34 tertiary hospitals in 18 Chinese cities. A total of 1 714 surgical patients hospitalized for 7-30 days with complete data were included. Standardized protocols were used to collect demographic data, clinical outcomes, and a range of laboratory results, including nutritional and hematological parameters. Heterogeneous effects of ALB on clinical outcomes were explored. Receiver operating characteristic (ROC) curves were used to determine cutoff values for infection-related complications. Correlation analyses and multiple linear regression models were used to identify independent predictors of the absolute change in ALB (?ALB).Results:Among the surgical patients, 69.7% (1 195/1 714) experienced a decline in ALB levels during their hospital stay, which was significantly associated with the occurrence of both infection- and non-infection-related complications. Simultaneously, a marked decrease in ALB was also significantly correlated with changes in nutritional and inflammatory status during hospitalization, worsening of gastrointestinal symptoms at discharge, and functional activity abnormalities (all P<0.05). ?ALB exhibited a close association with outcome variables such as infection-related complications. Based on the incidence of infection-related complications, a cutoff value for ALB was calculated, dividing patients into a high-risk group ( n=179) and a low-risk group ( n=1 535), and a statistically significant difference in the incidence of infection-related complications was found between these two groups ( P<0.05). Correlation analysis and multiple linear regression modeling revealed that female gender, a higher baseline ALB level, a poorer baseline inflammatory status, an exacerbation of inflammatory status, larger alterations in platelet-to-lymphocyte ratio, and the presence of infection-related complications were predictive factors for a decline in ALB levels among surgical patients during their hospital stay. Conclusions:?ALB serves as a critical indicator of the inflammatory-nutritional interplay, with its magnitude of decline effectively predicting clinical outcomes and nutritional status changes and guiding multidisciplinary interventions in surgical patients.

OBJECTIVE To conduct continuous targeted surveillance on patients undergoing pancreatoduodenecto-my in a three-A comprehensive hospital,to understand the current status of postoperative surgical site infection(SSI),identify risk factors and provide references for effective prevention and control measures.METHODS A targeted surveillance of SSI was conducted on 812 patients who underwent open pancreatoduodenectomy in the General Surgery Department of Qilu Hospital of Shandong University from 2020 to 2023.Statistical analysis was performed on various indicators,the incidence rate of SSI.RESULTS There were 42 cases of SSI in patients under-going pancreatoduodenectomy,with an incidence rate of 5.17％.Among them,there were 2 cases of deep surgi-cal incision infection and 40 cases of organ(or lacuna)infection.There was no statistically significant difference in the incidence rate of SSI across different years,but there was a decreasing trend over the years(P=0.227).Mul-tivariate logistic regression analysis showed that incision cleanliness(contamination)and intraoperative blood loss(＞250 ml)were risk factors for SSI,while the tumor location(pancreas)was a protective factor for SSI(P＜0.05).The surgeon-specific infection incidence rate ranged from 0.00％to 20.00％,with the highest infection rate observed in Surgeon No.1(20.00％).After adjustment,the top three surgeons with the highest specific in-fection rates were Surgeon No.1(50.00％),Surgeon No.5(34.49％)and Surgeon No.20(32.05％).Among the samples from 42 patients with SSI,70 pathogenic bacteria were detected,mainly Escherichia coli(18.57％)and Enterococcus faecium(14.29％).The hospital stay for patients with SSI after surgery was 25.00(20.00,34.00)days,while the hospital stay for patients without SSI was 19.00(16.00,24.00)days.Patients had an ex-tended hospital stay of 6 days due to SSI(P＜0.001).CONCLUSIONS SSI in patients undergoing pancreatoduode-nectomy is mainly organ(or lacuna)infection.Incision cleanliness(contamination)and intraoperative blood loss(＞250 ml)can increase the incidence rate of SSI in patients undergoing pancreatoduodenectomy.The specific in-fection rates vary among different surgeons,with the main pathogenic bacteria causing SSI being E.coli and E.faecium.The occurrence of SSI prolongs patients'hospital stay.

A case of small cerebral vascular disease and moderate hyperhomocysteinemia caused by methylenetetrahydrofolate reductase gene mutation is reported.The patient was a 61-year-old man who presented with tongue stiffness and slurred speech,bilateral hand numbness and lower limb weakness.He had a history of recurrent cerebral infarction,cerebral hemorrhage,accompanied by leukoencephalopathy and cerebral microhemorrhage etc.Blood homocysteine(Hcy)66.2 μmol/L.Head magnetic resonance imaging revealed subacute cerebral infarction and white matter lesions in right parieto-occipital lobe and left pressor corpus callosum.The skin pathology showed normal density of small fibers,infiltration of perivasculitis cells in the epidermis and dermis,and swelling of endothelial cells in a wide range of small vessels in the dermis.Whole exon sequencing indicated homozygous pathogenic mutation of MTHFR gene c.665C>T(p.A222V).After 1 month of treatment,Hcy decreased to 20.5 μmol/L.This report suggests that HHcy is not only associated with leucoencephalopathy,but also can lead to skin small vessel lesions.Attention should be paid to peripheral vascular screening in this population for early intervention of potential risks.