ObjectiveTo explore the effect of transcutaneous electrical acupoint stimulation （TEAS） on stress response in patients undergoing unilateral biportal endoscopy （UBE） and to identify optimal TEAS parameters. MethodsA total of 96 patients undergoing UBE were randomly grouped into total intravenous anesthesia （TIVA） group， acupuncture-assisted anesthesia with continuous waves （AACW） group， and acupuncture-assisted anesthesia with sparse-dense waves （AASDW） group， with 32 patients per group. All groups were given a standardized TIVA protocol. In the AACW group （100 Hz continuous wave stimulation） and the AASDW group （2/100 Hz sparse-dense wave stimulation）， TEAS intervention was applied to both bilateral Zusanli （ST36） and Sanyinjiao （SP6） 30 minutes before TIVA induction and continued until the end of the surgery. In the TIVA group， electrodes were only connected without electrical stimulation. The stress response indicators including cortisol （Cor） and adrenocorticotropic hormone （ACTH）， heart rate （HR）， mean arterial pressure （MAP）， and bispectral index （BIS） at before anesthesia induction （T0）， after tracheal intubation （T1）， during laminectomy （T2）， and 1 hour after surgery （T3） were compared across groups. The operation duration， anesthesia duration， extubation and recovery duration were recorded， as well as pain intensity including visual analogue scale （VAS）， and sedation level （by Ramsay sedation score） at 2， 6， 12 hours after surgery， and postoperative complications. ResultsThe AACW group and AASDW group had lower ACTH and COR levels at T1， T2 and T3， as well as lower HR and MAP levels at T1 and T2 than TIVA group， with AASDW group being lower than AACW group （P＜0.05）. At T3， the AASDW group had higher BIS than TIVA group and AACW group （P＜0.05）. No significant difference in operation duration was observed （P＞0.05）. The AACW group and AASDW group had shorter anesthesia， extubation and recovery duration than TIVA group， with AASDW group being the shortest （P＜0.05）. The VAS scores at 2 h， 6 h， and 12 h after surgery in the AACW and AASDW groups were lower than those in the TIVA group， with the AASDW group showing significantly lower scores than the AACW group （P＜0.05）. The Ramsay sedation scores in the AASDW group were lower than those in the AACW group at 2 h and 6 h after surgery （P＜0.05）. The total incidence of complications in the AASDW group was 6.25% （2/32）， significantly lower than 28.13% （9/32） in the TIVA group （P＜0.05）. ConclusionTEAS can effectively suppresses stress response in patients undergoing UBE， with the 2/100 Hz sparse-dense wave parameter being most effective， which can stabilize hemodynamics， accelerate recovery， improve postoperative sedation and analgesia quality， and reduces complications.

ObjectiveBased on the regulation of macrophage M2 polarization， this study aims to explore the molecular mechanism and action targets of the Qijia Rougan prescription and its key effector ingredients in anti-fibrosis， thereby providing a basis and reference for the development of new drugs for hepatic fibrosis. MethodsA rat model of hepatic fibrosis was established by subcutaneous injection of 40%CCl₄， followed by oral administration of Qijia Rougan granules. The volume of collagen fibers was detected using Masson staining， the fibrosis markers Collagen Ⅰ and α-SMA were detected using immunohistochemistry， the proportion of M2 macrophages was detected by flow cytometry. The expression levels of M2 macrophage phenotype markers CD163 and CD206 were detected using immunofluorescence double staining. Western blot was used to detect the levels of the transforming growth factor-β （TGF-β）， platelet derived growth factor subunit B （PDGFB）， interleukin-10 （IL-10）， phosphorylated Janus kinase 1 （p-JAK1）， and phosphorylated signal transducer and activator of transcription 6 （p-STAT6）. Real-time fluorescent quantitative PCR was used to detect the relative expression levels of JAK1， STAT6， Arginase 1（Arg1）， and Fizz1. Based on the theory of serum pharmacology， liquid chromatography-mass spectrometry and WENN analysis were used to obtain the active ingredients of Qijia Rougan prescription. Molecular docking and molecular dynamics simulation were performed to analyze the effector ingredients and their targets. The identified effector ingredients were interfered with IL-4-induced M2 polarization of RAW264.7 macrophage in vitro to validate the targets. ResultsQijia Rougan prescription significantly reduced the content of fibrosis markers α-SMA and Collagen Ⅰ， as well as collagen fiber content （P<0.05）. It decreased the proportion of M2 macrophages and the levels of related cytokines IL-10， TGF-β and PDGFB， and up-regulated the levels of p-JAK1 and p-STAT6 （P<0.05）. A total of 1 214 compounds were identified from Qijia Rougan prescription， medicated serum and blank serum， and 29 ingredients were finalized by Venn analysis， including 15 blood-entry prototypes and 14 drug metabolites. Molecular docking showed that enoxolone and berberine bound more strongly to JAK1， with binding free energies of -9.6 kcal·mol^-1（1 cal≈4.184 J） and -9.1 kcal·mol^-1， respectively. Molecular dynamics simulations showed that JAK1-enoxolone and JAK1-berberine exhibited stable simulation trajectories within 100 ns， with essentially identical conformations and high protein overlap before and after simulation. Their binding free energies were -25.18 5.0.81 kcal·mol^-1 and -27.39 7.0.85 kcal·mol^-1， respectively. The number of hydrogen bonds formed between JAK1 and enoxolone ranges from 0 to 5， and most of the time can be maintained at 2-3. In vitro intervention with enoxolone or berberine significantly reduced p-JAK1 and p-STAT6 levels （P<0.05）. ConclusionQijia Rougan prescription inhibits M2 macrophage polarization in hepatic fibrosis. Enoxolone and berberine are the key effector ingredients of Qijia Rougan prescription to inhibit macrophage M2 polarization through targeting JAK1 and modulating the JAK1/STAT6 signaling pathway， thereby ameliorating hepatic fibrosis. This study provides a basis for prescription optimization， clinical application and new drug development， as well as a reference for monolithic anti-hepatic fibrosis research.

Gastric cancer remains one of the most prevalent and lethal malignancies of the digestive tract worldwide,underscoring the urgent need for more effective targeted therapeutic strategies.Poly(ADP-ri-bose)polymerase(PARP)inhibitors have demonstrated remarkable efficacy in tumors with homologous recombination repair(HRR)deficiency;however,their clinical application in gastric cancer remains limited.Clinical evidence suggests that patients harboring Helicobacter pylori infection in combination with HRR gene mutations exhibit a significantly elevated risk of developing gastric cancer,thereby supporting the potential benefit of PARP inhibition in this setting.In this study,a kinase inhibitor library was screened in combination with the PARP inhibitor olaparib in gastric cancer cells.And we identify the cy-clin-dependent kinase 8/19(CDK8/19)inhibitor Senexin A as a compound that synergistically enhances the cytotoxic effect of PARP inhibition(P<0.05).Phenotypic validation using CCK-8 and colony for-mation assays demonstrated that the combination treatment significantly suppressed cellular proliferation and clonogenic potential compared to either monotherapy(P<0.0001).Mechanistically,alkaline comet assays revealed a significant increase in DNA damage in the combination treatment group relative to either single-agent group(P<0.0001),suggesting that the synergistic effect results from the exacerbation of DNA damage via impaired DNA repair mechanisms.In addition,treatment with CDK8/19 inhibitors a-lone markedly increased the formation of γH2AX and 53BP1 foci in irradiated gastric cancer cells(P<0.0001),indicating inhibition of DNA damage repair pathways.Transcriptome sequencing further re-vealed that CDK8/19 inhibition impacts critical cellular pathways,including DNA repair,cell cycle reg-ulation,and RNA splicing.Co-immunoprecipitation assays confirmed that inhibition of CDK8/19 kinase activity significantly reduces the phosphorylation level of PARP1,suggesting a potential regulatory inter-action.Immunohistochemical analysis of tumor and adjacent non-tumor tissues from gastric cancer pa-tients demonstrated that CDK8 is significantly overexpressed in tumor tissues,supporting its potential as both a prognostic biomarker and a therapeutic target.Collectively,this study elucidates a mechanistic ba-sis by which CDK8/19 inhibition enhances the sensitivity of gastric cancer cells to PARP inhibitors.These findings provide a strong rationale for the combined use of CDK8/19 and PARP inhibitors as a tar-geted therapeutic strategy and offer promising translational implications for advancing personalized medi-cine in gastric cancer treatment.

Aim To investigate the effect of neogam-bogic acid(NGA)on inducing ferroptosis in osteosar-coma K7M2 cells and subcutaneous transplanted tumor mice and explore the underlying mechanism.Methods MTT assay was employed to detect the effect of NGA(1,2,4,8,16,32,64,128 μmol·L-1)on cell prolif-eration,and the IC50 value was calculated.Calcein AM assay was used to detect cell viability.Transwell was applied to detect cell invasion.TEM was utilized to ob-serve the mitochondria morphology.K7M2 cells were subjected to treat with ferroptosis inducers erastin(Era)and inhibitors ferrostatin-1(Fer-1)to assess the levels of MDA,GSH,Fe2+,and LDH.RT-qPCR and Western blot were used to detect the mRNA and protein expression of STAT3,GPX4,and SLC7A11.A transplanted tumor model was established and treated with NGA to assess the impact of it on tumor growth and ferroptosis in vivo.HE staining was applied to ana-lyze the pathological status of tumor tissues.Nile red fluorescence staining was applied to detect the level of lipid components in tumor tissues.Results The pro-liferation,viability and invasion ability of K7M2 cells were significantly reduced after treatment with NGA at different concentrations(P＜0.05),and typical fea-tures of ferroptosis such as decreased mitochondrial vol-ume and reduced mitochondrial spine were observed.Compared to the control,the expression of MDA,Fe2+and LDH significantly increased(P＜0.01),while the content of GSH significantly decreased(P＜0.01).The ferroptosis in osteosarcoma was enhanced by the erastin,while inhibited by ferrostatin-1.In terms of mechanism,NGA inhibited the mRNA and protein ex-pression levels of STAT3,GPX4 and SLC7A11(P＜0.05).In vivo experiments confirmed that NGA signif-icantly improved the pathological state of tumor tissues,inhibited tumor growth,and induced ferroptosis in os-teosarcoma tissue cells.Conclusion NGA induces ferroptosis in osteosarcoma cells both in vitro and in vi-vo by inhibiting the STAT3/GPX4/SLC7A11 signaling axis,thereby exerting an anti-osteosarcoma effect.

Objective To analyze the status and influencing factors of Helicobacter pylori(Hp)infection in the occupational population of Chengdu city.Methods A retrospective analysis was conducted on the general data of 8860 occupational population who underwent health examinations in our hospital from June 2021 to June 2023.All study subjects underwent 14 C urea breath test during health check ups.Analyze the Hp infection status of 8860 occupational population,and use logistic regression analysis(single factor and multiple factor)to explore the influencing factors of Hp infection in occupational population in Chengdu.Results Among the 8860 occupational population undergoing physical examinations in Chengdu,2890 cases were positive for Hp infection,with a total Hp infection rate of 32.62%.Univariate analysis found that occupational groups with age≥40 years,male,BMI<18.5 kg/m2(underweight)/24.0 kg/m2～27.9 kg/m2(overweight)/≥28 kg/m2(obese),workers,history of alcohol consumption,smoking,unclean diet,family history of Hp infection,and history of spicy and jelly diet had a higher Hp infection rate(P<0.05).Multivariate analysis showed that age≥40 years old,low BMI,overweight,obesity,alcohol consumption history,unclean diet history,family history of Hp infection,and spicy diet history were all risk factors affecting Hp infection in the occupational population of Chengdu(P<0.05).Conclusion The positive rate of Hp infection in the occupational population of Chengdu is relatively high,associated with age,alcohol consumption history,BMI,history of unclean diet,family history of Hp infection,and history of spicy eating.Therefore,attention should be paid to the Hp infection status of the occupational population.It is not only necessary to strengthen Hp infection publicity and education,but also to intervene in its risk factors early,in order to reduce and prevent Hp infection in the occupational population.

Objective To analyze the correlation between lesion volume,lesion mass,and maximum lesion diameter in the assessment of advanced hepatocarcinoma with lung metastasis,and to evaluate the application value of total volume response and total mass response of lung metastatic lesions in efficacy assessment.Methods A retrospective analysis was conducted on the CT imaging data of 20 patients clinically confirmed with hepatocarcinoma and lung metastases,followed by subsequent follow-up to monitor their survival outcomes.Volume measurement software was used to measure the volume of lesions before and after treatment.We recored lesion diameter,volume measurements and CT values,calculated the mass of the lesions.The correlation between lesion volume,mass and diameter was analyzed,as well as the correlation between the change rates of volume,mass and lesion diameter.Additionally,the total volume and total mass of all lesions were calculated.The correlation between the change rates of total volume/total mass and the change rate of pulmonary lesion diameter under the RECIST 1.1 criteria,as well as the correlation with changes in patients'tumor markers,were analyzed.Furthermore,the overall volume response and overall mass response of lesions were evaluated based on changes in total volume and total mass,and their consistencies with the RECIST 1.1 criteria for efficacy evaluation were analyzed.Finally,univariate Cox regression analysis was performed to explore the association between these variables and patient survival outcomes.Results There was strong correlation between lesion volume,mass and tumor diameter(r=0.771,0.775),between the rate of change in mass and the rate of change in lesion diameter(r=0.846),and between the rates of change in total volume/total mass and the rate of change in pulmonary lesion diameter under the RECIST 1.1 criteria(r=0.800,0.896).The correlation between the rates of change in total volume/total mass and patients'tumor markers was not statistically significant.There was moderate correlation between the rate of change in volume and the rate of change in lesion diameter(r=0.692).The evaluation results of total volume response and total mass response for pulmonary lesions in advanced hepatocarcinoma with lung metastasis were generally consistent with the RECIST 1.1 criteria(Kappa=0.486,0.426).Univariate Cox regression analysis revealed that total lesion volume(P=0.047)and total lesion mass(P=0.049)were independent prognostic factors for survival outcomes.Conclusion Lesion volume,mass,and diameter,as well as their respective change rates,were found to be interrelated.Furthermore,total lesion volume and total lesion mass were identified as independent prognostic factors for survival outcomes.The total volume response and total mass response are promising evaluation methods in evaluating the efficacy of lung metastasis of hepatocarcinoma,which are different from the RECIST 1.1 evaluation criteria.

Objective To investigate the association of spleen volume with the risk of non-alcoholic fatty liver disease(NAFLD)as well as their causal relationship.Methods We included 90 NAFLD cases and 47 healthy controls who had received contrast-enhanced computed tomography(CT)scan of the abdomen at the Second Affiliated Hospital of Xi'an Jiaotong University from November 2022 to November 2023.We conducted three-dimensional reconstruction of the spleen through a deep learning network model using a two-stage coarse-to-fine segmentation approach.We compared the two groups using the two-sample t test or Mann-Whitney U test for continuous data and using the chi-square test for categorical data;evaluated the correlation between spleen volume and liver function indicators through Pearson correlation or Spearman rank correlation analyses;determined the factors influencing the development of NAFLD through multivariable Logistic regression analysis;and further assessed the casual relationship between spleen volume and NAFLD using the inverse variance-weighted two-sample Mendelian randomization(IVW-MR)method.Results Spleen volume was significantly larger in NAFLD cases than in controls(272.93±104.16 vs 204.37±81.20 cm3,P<0.001).The Spearman rank correlation analysis showed that spleen volume was positively correlated with the hepatic steatosis index(rs=0.422,P<0.001)and gamma-glutamyl transferase levels(rs=0.211,P=0.047)in patients with NAFLD.The multivariable Logistic regression analysis indicated that spleen volume was an independent risk factor for the development of NAFLD(odds ratio[OR]=1.01,95%confidence interval[CI]:1.00-1.02,P=0.049).The IVW-MR analysis detected a causal relationship between spleen volume and NAFLD(OR=1.16,95%CI:1.05-1.28,P=0.005).Conclusion Increased spleen volume may be a risk factor for the development and progression of NAFLD.Further studies are still needed to investigate the specific mechanism.

Objective:To investigate the predictive value of color Doppler ultrasound combined with electrocardio-gram for right heart dys function in patients with pulmonary heart disease(PHD).Methods:A total of 100 PHD patients admitted in Dongcheng Branch of First Affiliated Hospital of Anhui Medical University between January 2020 and December 2023 were retrospectively analyzed.According to results of 6min walking test(6MWT),pa-tients were divided into good right heart function group(n=64,≥350m)and right heart dysfunction group(n=36,＜350m).The indexes of cardiac color ultrasound[isovolumic relaxation time(IVRT),isovolumetric contraction time(IVCT)and right ventricular Tei index],ECG[24h mean R-R interval standard deviation(SDNN),normal R-R interval standard deviation per 5min(SDANN)and the ratio of low frequency components to high frequency components(LF/HF)]were compared between two groups.Receiver operating characteristic(ROC)curve was drawn to analyze the diagnostic value of color Doppler ultrasound,ECG and their combination for right heart dys-function in PHD patients.Spearman correlation coefficient was used to analyze the association of color Doppler ul-trasound,ECG and their combination with right heart dysfunction in PHD patients.Results:Compared with those in good right heart function group,patients in right heart dysfunction group had significant higher IVRT[(120.64±14.08)ms vs.(97.87±10.93)ms],IVCT[(84.28±12.33)ms vs.(71.92±10.61)ms]and Tei index[(0.85±0.11)vs.(0.63±0.07)](P＜0.001 all),and significant lower SDNN[(75.52±12.58)ms vs.(85.58±11.75)ms],SDANN[(63.86±10.92)ms vs.(76.75±11.71)ms]and LF/HF[(1.33±0.19)vs.(1.84±0.27)](P＜0.001 all).ROC curve indicated that the AUC of color Doppler ultrasound combined ECG in diagnosing right heart dysfunction in PHD patients was 0.911(95％CI 0.838～0.959),which was significantly higher than those of color Doppler ultrasound[0.775(95％CI 0.681～0.853),Z=2.404,P=0.016]and ECG[0.688(95％CI 0.588～0.777),Z=3.968,P=0.001]alone.Spearman correlation analysis indicated that there was a significant positive correlation of color Doppler ultrasound(r=0.547),ECG(r=0.375)and their combination(r=0.810)with right heart dysfunction in PHD patients(P＜0.001 all),and the correlation between combined detection and right heart dysfunction in PHD patients was significantly higher.Conclusion:Color Doppler ultrasound combined with ECG possesses high diagnostic performance for right heart dysfunction in PHD patients.

Hospital pharmacy research is significant in enhancing the level of rational drug use,improving the quality of pharmacy services,and promoting the improvement of drug treatment effects.To guarantee the standardization of hospital pharmacy research,the compilation team of"Hospital Pharmacy Research Standards"adheres to the principles of scientificity,universality,guidance,and operability,combs through the key management contents from three aspects,namely,relevant national policy docu-ments,relevant domestic and international standards and norms,and literature analysis,combines with the actual working condition of hospital pharmacy research,and formulates the standards after several rounds of opinion collection and expert argumentation.This paper analyzes the key contents of the standard,including basic requirements,research process management,and research re-sults management,to provide guidance and reference for hospital pharmacy researchers to understand the standard in-depth and further improve the standardization of hospital pharmacy research.

Aim To investigate the effect of neogam-bogic acid(NGA)on inducing ferroptosis in osteosar-coma K7M2 cells and subcutaneous transplanted tumor mice and explore the underlying mechanism.Methods MTT assay was employed to detect the effect of NGA(1,2,4,8,16,32,64,128 μmol·L-1)on cell prolif-eration,and the IC50 value was calculated.Calcein AM assay was used to detect cell viability.Transwell was applied to detect cell invasion.TEM was utilized to ob-serve the mitochondria morphology.K7M2 cells were subjected to treat with ferroptosis inducers erastin(Era)and inhibitors ferrostatin-1(Fer-1)to assess the levels of MDA,GSH,Fe2+,and LDH.RT-qPCR and Western blot were used to detect the mRNA and protein expression of STAT3,GPX4,and SLC7A11.A transplanted tumor model was established and treated with NGA to assess the impact of it on tumor growth and ferroptosis in vivo.HE staining was applied to ana-lyze the pathological status of tumor tissues.Nile red fluorescence staining was applied to detect the level of lipid components in tumor tissues.Results The pro-liferation,viability and invasion ability of K7M2 cells were significantly reduced after treatment with NGA at different concentrations(P＜0.05),and typical fea-tures of ferroptosis such as decreased mitochondrial vol-ume and reduced mitochondrial spine were observed.Compared to the control,the expression of MDA,Fe2+and LDH significantly increased(P＜0.01),while the content of GSH significantly decreased(P＜0.01).The ferroptosis in osteosarcoma was enhanced by the erastin,while inhibited by ferrostatin-1.In terms of mechanism,NGA inhibited the mRNA and protein ex-pression levels of STAT3,GPX4 and SLC7A11(P＜0.05).In vivo experiments confirmed that NGA signif-icantly improved the pathological state of tumor tissues,inhibited tumor growth,and induced ferroptosis in os-teosarcoma tissue cells.Conclusion NGA induces ferroptosis in osteosarcoma cells both in vitro and in vi-vo by inhibiting the STAT3/GPX4/SLC7A11 signaling axis,thereby exerting an anti-osteosarcoma effect.