Mammalian target of rapamycin inhibitor (mTORi) not only exert strong immunosuppressive effects, but also possess multiple potential benefits, including antiviral, antitumor, antifibrotic, and anti-aging properties. Their long-term efficacy in the field of organ transplantation has been well established, and they have been widely applied in clinical practice. However, the adverse effects of mTORi-such as impaired wound healing, oral ulcers, anemia, proteinuria, hyperglycemia, dyslipidemia, pneumonia, lymphedema, and angioedema-remain a challenge in clinical settings. In immunosuppressive regimens for organ transplantation, mTORi are used in diverse combination therapies and exhibit considerable inter-individual variability. This article briefly reviews recent research progress on mTORi in solid organ transplantation (SOT) and discusses strategies for their rational application, aiming to provide useful insights for clinical practice.

Objective:To investigate the impact of early invasive arterial blood pressure (IBP) monitoring on survival and neurological outcomes in out-of-hospital cardiac arrest (OHCA) patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR).Methods:This retrospective cohort study analyzed 44 OHCA patients receiving ECPR between January 2021 and January 2023. Patients were divided into: Early intervention group : IBP established within 3 min of ECMO initiation; Late intervention group : IBP established after ICU admission. Baseline characteristics, ECMO parameters, and clinical outcomes were compared. Multivariable logistic regression (adjusted for age, initial rhythm, etc.) and Spearman's correlation were used.Results:This study included a total of 44 patients treated with OHCA and ECPR, divided into an early intervention group of 23 cases and a late intervention group of 21 cases. The early intervention group showed significantly higher: Survival to discharge (43.5% vs. 9.5%, P<0.05), Good neurological recovery (CPC 1-2: 34.8% vs. 9.5%, P<0.05).Early intervention independently predicted survival (adjusted OR=18.84, 95% CI:1.97-179.98, P=0.01). Stratified analysis by pH (cutoff 7.0) demonstrated consistent benefits in both pH>7.0 ( aOR=0.392, 95% CI:0.106-0.678) and pH≤7.0 subgroups ( aOR=0.385, 95% CI: 0.075-0.695; interaction P=0.183). Early IBP positively correlated with CPC scores ( ρ=0.40, P=0.007). Conclusions:Early IBP monitoring significantly improves survival and neurological outcomes in OHCA-ECPR patients, supporting its integration into standardized protocols.

Objective To investigate the current status of job competency of full-time personnel who engaged in gastrointestinal endoscope cleaning and disinfection in medical institutions in Hubei Province,analyze the influencing factors,and provide reference for conducting the training for full-time personnel in gastrointestinal endoscope clea-ning and disinfection.Methods Through expert consultation and revision,as well as forming of questionnaire,an online survey was conducted.The questionnaire was filled out by full-time personnel who engaged in endoscope cleaning and disinfection in the endoscopy centers/rooms in medical institutions.Results A total of 195 full-time personnel engaged in cleaning and disinfecting gastrointestinal endoscopes in 185 medical institutions participated in the survey,with a self-assessment score of(4.48±0.41)point for job competency.Univariate analysis showed that there were statistically significant differences in the self-assessment scores of job competency based on different le-vels of training,training frequency,income satisfaction,and daily diagnosis and treatment volume(all P＜0.05).Multiple linear regression analysis indicated that full-time personnel with working years＞10 years,satisfying with their income,participating in provincial/national level training,receiving training at least once per year,and having an average daily diagnosis and treatment volume＞50 cases had higher self-assessment score of job competency(all P＜0.05).Conclusion In order to enhance the job competency of personnel who engage in gastrointestinal endo-scope cleaning and disinfection,it is recommended to encourage the participation in provincial/national training,and the hospital-wide training should emphasize the application and disposal of cleaning,disinfection,and storage de-vices of gastrointestinal endoscope,as well as disinfection knowledge,and encourage personnel to conduct relevant research.

Objective To investigate the current status of job competency of full-time personnel who engaged in gastrointestinal endoscope cleaning and disinfection in medical institutions in Hubei Province,analyze the influencing factors,and provide reference for conducting the training for full-time personnel in gastrointestinal endoscope clea-ning and disinfection.Methods Through expert consultation and revision,as well as forming of questionnaire,an online survey was conducted.The questionnaire was filled out by full-time personnel who engaged in endoscope cleaning and disinfection in the endoscopy centers/rooms in medical institutions.Results A total of 195 full-time personnel engaged in cleaning and disinfecting gastrointestinal endoscopes in 185 medical institutions participated in the survey,with a self-assessment score of(4.48±0.41)point for job competency.Univariate analysis showed that there were statistically significant differences in the self-assessment scores of job competency based on different le-vels of training,training frequency,income satisfaction,and daily diagnosis and treatment volume(all P＜0.05).Multiple linear regression analysis indicated that full-time personnel with working years＞10 years,satisfying with their income,participating in provincial/national level training,receiving training at least once per year,and having an average daily diagnosis and treatment volume＞50 cases had higher self-assessment score of job competency(all P＜0.05).Conclusion In order to enhance the job competency of personnel who engage in gastrointestinal endo-scope cleaning and disinfection,it is recommended to encourage the participation in provincial/national training,and the hospital-wide training should emphasize the application and disposal of cleaning,disinfection,and storage de-vices of gastrointestinal endoscope,as well as disinfection knowledge,and encourage personnel to conduct relevant research.

AIM:To investigate the therapeutic effects and potential mechanism of pachymic acid(PA)on li-popolysaccharide(LPS)-induced acute kidney injury(AKI)in mice.METHODS:(1)Genes related to AKI were screened using the DAVID database.Core genes were identified by intersecting related genes and analyzed using Cyto-scape software.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were performed through the DAVID database for the cross-targets.Molecular docking and activity assays were conducted on the primary core targets.(2)A total of 100 C57BL/6J mice were randomly divided into five groups:normal control(NC),model(LPS),solvent control(LPS+DMSO),and treatment groups(LPS+PA-10 and LPS+PA-20),with 20 mice in each group.The LPS-AKI model was established by intraperitoneal injection of 18 mg/kg LPS.The treatment groups received 10 mg/kg and 20 mg/kg PA,respectively,and the solvent control group was administered an equivalent dose of DMSO.Mice were euthanized 24 h after injection.Serum was collected for biochemical analysis,and Western blot was used to detect neutro-phil gelatinase-associated lipocalin(NGAL),kidney injury molecule-1(KIM-1),caspase-3,cleaved caspase-3,interleu-kin-1β(IL-1β),and monocyte chemoattractant protein-1(MCP-1)protein expression.RT-qPCR was employed to detect inflammatory factor mRNA levels.Molecular docking was used to simulate the optimal binding site of PA to caspase-3.En-zyme activity assays were performed to assess caspase protein activity,and renal lesions were observed via hematoxylin and eosin(HE)staining.Apoptosis was detected by TUNEL staining.RESULTS:(1)Thirty-one potential targets of PA against AKI were identified through network pharmacology.GO and KEGG enrichment analyses indicated that these tar-gets were primarily involved in immune response,inflammatory processes,apoptosis and survival,angiogenesis and hemo-dynamics,oxidative stress,and endoplasmic reticulum stress.Key targets included CASP3(caspase-3),PTGS2,BCL2,CCL2,and CYP219.(2)PA treatment improved renal function and reduced tubular epithelial injury.It significantly de-creased NGAL,KIM-1,and cleaved caspase-3 protein levels,as well as inflammatory factors TNF-α,IL-1β,and MCP-1 mRNA and protein expression.PA also reduced apoptosis of renal tubular epithelial cells.Enzyme activity assays and mo-lecular docking revealed that PA exerted its anti-apoptotic effect by directly binding to caspase-3,thereby inhibiting its ac-tivation by caspase-8.CONCLUSION:PA demonstrated a therapeutic effect in LPS-AKI,potentially through the inhibi-tion of inflammatory factor synthesis and release,as well as the inhibition of caspase-3 activation by caspase-8,reducing apoptosis in renal tubular epithelial cells.

AIM:To investigate the therapeutic effects and potential mechanism of pachymic acid(PA)on li-popolysaccharide(LPS)-induced acute kidney injury(AKI)in mice.METHODS:(1)Genes related to AKI were screened using the DAVID database.Core genes were identified by intersecting related genes and analyzed using Cyto-scape software.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were performed through the DAVID database for the cross-targets.Molecular docking and activity assays were conducted on the primary core targets.(2)A total of 100 C57BL/6J mice were randomly divided into five groups:normal control(NC),model(LPS),solvent control(LPS+DMSO),and treatment groups(LPS+PA-10 and LPS+PA-20),with 20 mice in each group.The LPS-AKI model was established by intraperitoneal injection of 18 mg/kg LPS.The treatment groups received 10 mg/kg and 20 mg/kg PA,respectively,and the solvent control group was administered an equivalent dose of DMSO.Mice were euthanized 24 h after injection.Serum was collected for biochemical analysis,and Western blot was used to detect neutro-phil gelatinase-associated lipocalin(NGAL),kidney injury molecule-1(KIM-1),caspase-3,cleaved caspase-3,interleu-kin-1β(IL-1β),and monocyte chemoattractant protein-1(MCP-1)protein expression.RT-qPCR was employed to detect inflammatory factor mRNA levels.Molecular docking was used to simulate the optimal binding site of PA to caspase-3.En-zyme activity assays were performed to assess caspase protein activity,and renal lesions were observed via hematoxylin and eosin(HE)staining.Apoptosis was detected by TUNEL staining.RESULTS:(1)Thirty-one potential targets of PA against AKI were identified through network pharmacology.GO and KEGG enrichment analyses indicated that these tar-gets were primarily involved in immune response,inflammatory processes,apoptosis and survival,angiogenesis and hemo-dynamics,oxidative stress,and endoplasmic reticulum stress.Key targets included CASP3(caspase-3),PTGS2,BCL2,CCL2,and CYP219.(2)PA treatment improved renal function and reduced tubular epithelial injury.It significantly de-creased NGAL,KIM-1,and cleaved caspase-3 protein levels,as well as inflammatory factors TNF-α,IL-1β,and MCP-1 mRNA and protein expression.PA also reduced apoptosis of renal tubular epithelial cells.Enzyme activity assays and mo-lecular docking revealed that PA exerted its anti-apoptotic effect by directly binding to caspase-3,thereby inhibiting its ac-tivation by caspase-8.CONCLUSION:PA demonstrated a therapeutic effect in LPS-AKI,potentially through the inhibi-tion of inflammatory factor synthesis and release,as well as the inhibition of caspase-3 activation by caspase-8,reducing apoptosis in renal tubular epithelial cells.

Mammalian target of rapamycin inhibitor (mTORi) not only exert strong immunosuppressive effects, but also possess multiple potential benefits, including antiviral, antitumor, antifibrotic, and anti-aging properties. Their long-term efficacy in the field of organ transplantation has been well established, and they have been widely applied in clinical practice. However, the adverse effects of mTORi-such as impaired wound healing, oral ulcers, anemia, proteinuria, hyperglycemia, dyslipidemia, pneumonia, lymphedema, and angioedema-remain a challenge in clinical settings. In immunosuppressive regimens for organ transplantation, mTORi are used in diverse combination therapies and exhibit considerable inter-individual variability. This article briefly reviews recent research progress on mTORi in solid organ transplantation (SOT) and discusses strategies for their rational application, aiming to provide useful insights for clinical practice.

OBJECTIVES: Sepsis remains a major global health challenge, yet specific diagnostic biomarkers are still lacking. This study aims to investigate the causal relationship between B7 homologue 3 (B7-H3) and sepsis susceptibility, severity, and clinical outcomes using Mendelian randomization (MR) analysis, in order to evaluate its potential as a biomarker. METHODS: Genetic data related to sepsis (including overall sepsis, sepsis-related mortality with 28 days, severe sepsis, and severe sepsis with 28-day mortality) were extracted from genome-wide association study (GWAS) datasets. Single nucleotide polymorphisms (SNPs) associated with B7-H3 were selected as instrumental variables. The inverse-variance weighted (IVW) was used as the primary approach for causal effect estimation, while weighted median (WME) and MR-Egger regression served as supplementary methods. Additionally, a constrained maximum likelihood-model average (cML-MA) approach was employed to enhance the reliability of causal effect estimation. Cochran's Q test was conducted to assess heterogeneity, and MR-PRESSO along with the MR-Egger intercept method were used to detect horizontal pleiotropy. Sensitivity analyses were performed using the leave-one-out method. A reverse MR analysis was performed with sepsis as the exposure and B7-H3 as the outcome to exclude potential reverse causation. RESULTS: IVW analysis indicated a significant positive causal association between B7-H3 and sepsis susceptibility, severity, and clinical outcomes. A genetically predicted 1-standard deviation (SD) increase in B7-H3 levels was associated with a 10.4% increased risk of sepsis (OR=1.104, 95% CI 1.021 to 1.194, P=0.013), a 26.2% increased risk of sepsis-related 28-day mortality (OR=1.262, 95% CI 1.078 to 1.476, P=0.004), a 22.3% increased risk of severe sepsis (OR=1.223, 95% CI 1.023 to 1.463, P=0.027), and a 60.2% increased risk of severe sepsis with 28-day mortality (OR=1.602, 95% CI 1.119 to 2.294, P=0.010). The causal effect direction remained consistent across IVW, WME, MR-Egger, and cML-MA analyses, reinforcing the robustness and reliability of the results. Cochran's Q test showed no heterogeneity (P>0.05), while MR-PRESSO and MR-Egger intercept tests indicated no evidence of horizontal pleiotropy (both P>0.05). The leave-one-out analysis showed that removing individual SNPs did not significantly alter the causal estimates. Reverse MR analysis showed no causal association between sepsis and B7-H3. CONCLUSIONS B7-H3 may serve as an important biomarker for sepsis, as it is closely associated with sepsis susceptibility, severity, and clinical outcomes.
Sepsis/mortality* ; Humans ; Mendelian Randomization Analysis ; Polymorphism, Single Nucleotide ; B7 Antigens/genetics* ; Prognosis ; Genome-Wide Association Study ; Biomarkers ; Genetic Predisposition to Disease

AIM:Using bioinformatics analysis methods to identify the hub genes involved in myocardial isch-emia-reperfusion injury(MIRI).METHODS:Firstly,the rat MIRI related dataset GSE122020,E-MEXP-2098,and E-GEOD-4105 were downloaded from the database.Secondly,differentially expressed genes(DEGs)were screened from each dataset using the linear models for microarray data(limma)package,and robust DEGs were filtered using the robust rank aggregation(RRA)method.In addition,the surrogate variable analysis(SVA)package was used to merge all datas-ets into one,and merged DEGs were screened using the limma package.The common DEGs were obtained by taking the intersection of the two channels of DEGs.Next,the protein-protein interaction(PPI)network of common DEGs was con-structed,and the hub genes were identified using the density-maximizing neighborhood component(DMNC)algorithm.The receiver operating characteristic curve(ROC)was plotted to evaluate the diagnostic performance of the hub gene.Then,the mRNA and protein expression levels of hub genes were detected in the rat MIRI model,and the literature re-view analysis was carried out on the involvement of hub genes in MIRI.Finally,the gene set enrichment analysis(GSEA)was performed on hub gene to further reveal the possible mechanism in mediating MIRI.RESULTS:A total of 143 robust DEGs and 48 merged DEGs were identified.After taking the intersection of the two,48 common DEGs were obtained.In the PPI network of common DEGs,5 hub genes were screened out,namely MYC proto-oncogene bHLH transcription fac-tor(MYC),prostaglandin-endoperoxide synthase 2(PTGS2),heme oxygenase 1(HMOX1),caspase-3(CASP3),and plasminogen activator urokinase receptor(PLAUR).The ROC results showed that the area under the curve values for all hub genes were greater than 0.8.MYC,PTGS2,CASP3,and PLAUR showed high mRNA and protein expression in rat MIRI,while there was no difference in mRNA and protein expression for HMOX1.The literature review revealed that among the 5 hub genes,only PLAUR has not been reported to be involved in MIRI.The GSEA results for PLAUR indicat-ed that its functional enrichment mainly focused on pathways such as NOD-like receptor signaling pathway,P53 signaling pathway,Toll-like receptor signaling pathway,apoptosis,and fatty acid metabolism.CONCLUSION:MYC,PTGS2,CASP3,HMOX1,and PLAUR are involved in the pathological process of MIRI.PLAUR is a potential hub gene that can mediate MIRI by regulating pathways such as NOD like receptor signaling,P53 signaling,Toll like receptor signaling,cell apoptosis,and fatty acid metabolism.The results can provide reference for further investigation into the molecular mechanisms and therapeutic targets of MIRI.

Objective:To evaluate the safety and efficacy of tumor-treating fields (TTFields) and chemoradiation in patients with high-grade glioblastoma.Methods:Clinical data of 38 patients admitted to the Jiangsu Cancer Hospital from September 2021 to May 2023 who were diagnosed with high-grade glioblastoma (36 cases of World Health Organization grade Ⅳ and 2 cases of grade Ⅲ) were retrospectively analyzed. All patients received TTFields combined with concurrent chemoradiation after surgery. Response assessment in neuro-oncology (RANO) criteria was used to evaluate the glioma responses as tumor remission, stable or progression. Common terminology criteria for adverse events v5.0 and TTFields related skin adverse reaction (dAE) criteria were used to evaluate the adverse events. Treatment compliance was assessed by data on the NovoTTF-200A therapeutic device, calculated as a percentage of daily TTFields usage time. Survival analysis was estimated by the Kaplan-Meier method and compared by the log-rank test.Results:The median duration of treatment with TTFields in 38 patients was 20 h (rang: 2.4-22.6 h), and the median treatment compliance was 83% (range: 10%-94%). After 42 days of TTFields combined with concurrent chemoradiation, 12 patients who underwent complete tumor resection were assessed as stable according to RANO criteria. Among the 26 patients who underwent partial tumor resection, 23 (88%) were evaluated as disease remission according to RANO criteria. The 7-, 10-, 13-month progression-free survival rate was 81.0%、64.0%、49.5%, repectively. The common adverse events included grade 1 (45%) and grade 2 (8%) dAE, without grade 3-4 dAE. Typical presentations included contact dermatitis, blisters, lesions or ulcers, and abscesses. The median follow-up time was 10.0 months (range: 1.6-21.3 months). At follow-up as of July 2023, 26 of the 38 patients were stable and 12 had disease progression (8 died).Conclusion:The preliminary results show that TTFields combined with chemoradiation is effective, safe and reliable treatment for high-grade glioblastoma.