Objective To construct an animal model of dilated cardiomyopathy(DCM)with heart failure toxin syndrome that conforms to the characteristics of traditional Chinese medicine(TCM)syndrome and identify potential biomarkers or intervention targets for DCM with heart failure toxin syndrome.Methods Fifteen male SD rats were divided into a blank control,doxorubicin,or DCM with heart failure toxin syndrome group using a random number table method,with five rats per group.The doxorubicin group received intraperitoneal injection of doxorubicin at a dose of 1.25 mg/kg,administered on the first and fourth days of each week,along with a standard diet.The DCM with heart failure toxin syndrome group,in addition to the doxorubicin treatment,was given 42％white liquor(10 mL/kg)via gavage every other day,along with a 45％high-fat feed and 10％fructose water.The blank control group received intraperitoneal injection of an equivalent volume of phosphate-buffered saline at the same time points as the doxorubicin group,along with a standard diet.The model was established for 10 weeks.At the fourth and tenth weeks of modeling,echocardiography was performed to measure left ventricular ejection fraction(LVEF),fractional shortening(FS),systolic left ventricular posterior wall thickness(LVPWs),diastolic left ventricular posterior wall thickness,systolic left ventricular internal diameter(LVIDs),and diastolic left ventricular internal diameter(LVIDd);macroscopic changes in fur color of the rats were assessed using the red-green-blue colorimetric method.After modeling,the open field test was conducted to evaluate the exercise tolerance of the rats,and the grip strength test was performed to assess changes in forelimb grip strength.Hematoxylin-eosin,Masson,and wheat germ agglutinin staining were used to evaluate pathological changes in cardiac tissue.Bulk RNA sequencing analysis was performed to identify differentially expressed genes(DEGs)in the hearts of rats between the blank control and the DCM with heart failure toxin syndrome groups.Using DCM,the Blue value of rat fur color,and forelimb grip strength as phenotypic traits,weighted gene co-expression network analysis(WGCNA)was performed to screen for characteristic module gene sets(MEs)associated with DCM with heart failure toxin syndrome.Overlapping analysis was performed on DEGs,immune-related gene sets,and MEs,and the intersecting genes were identified as potential biomarkers or intervention targets for DCM with heart failure toxin syndrome.The sensitivity and specificity of these targets were evaluated using receiver operating characteristic(ROC)curve analysis.Results Compared with the blank control group,at the tenth week of modeling,the LVEF,FS,and LVPWs of rats in the doxorubicin group and the DCM with heart failure toxin syndrome group decreased,whereas LVIDs and LVIDd increased,and the movement distance of the open field test and forelimb grip strength were reduced(P＜0.05).At the 10th week of modeling,the Blue value of fur color in the DCM with heart failure toxin syndrome group was significantly lower than that of the blank control and doxorubicin groups(P＜0.05).Compared with the blank control group,rats in the doxorubicin and DCM with heart failure toxin syndrome groups exhibited significant cardiac dilation and increased immune cell infiltration in cardiac tissue,accompanied by collagen deposition and cardiomyocyte hypertrophy.Bulk RNA sequencing identified 2,003 DEGs,including 1,082 downregulated genes and 921 upregulated genes.WGCNA results revealed that the MEturquoise module had the strongest positive correlation with DCM and the strongest negative correlation with the Blue value and forelimb grip strength.The overlapping analysis identified four intersecting genes:bone morphogenetic protein 6(Bmp6),serine-threonine-protein kinase 1(Pak1),proto-oncogene JunD(JunD),and S100 calcium-binding protein A3(S100A3).ROC curve analysis demonstrated that these four genes exhibited high sensitivity and specificity for DCM with heart failure toxin syndrome.Conclusion The rat model constructed by intraperitoneal injection of doxorubicin combined with a high-fat feed,fructose water,and white liquor gavage closely aligns with the characteristics of the DCM with heart failure toxin syndrome.Bmp6,JunD,Pak1,and S100A3 are potential biomarkers or therapeutic targets for DCM heart failure toxin syndrome.

This study was aimed at developing an in vitro fluorescent substrate assay for the activity of leucyl aminopeptid-ase(LAP)from Echinococcus multilocularis and comparing it with the chemical chromogenic substrate enzyme activity assay.Through the establishment of reaction conditions for the fluorescent substrate-based in vitro enzyme activity assay,we com-pared the differences between the fluorescent substrate L-Leucine-7-amido-4-methylocoumarin(Leu-AMC)and the chemical chromogenic substrate L-Leucine-4-nitroanilide(Leu-pNA)through molecular docking,inhibition rates,and precision measures.Molecular docking revealed that the fluorescent substrate Leu-AMC had higher affinity for the protein than the chemical chromogenic substrate Leu-pNA.Through analysis of the effects of varying reaction conditions on fluorescence intensi-ty,we optimized the fluorescent substrate enzyme activity assay to demonstrate favorable performance at a reaction temperature of 37℃,a pH of 9.0,a protein concentration of 800 nmol/L,and a reaction duration of 60 minutes.Leu-AMC exhibited significant and distinct responses at a 5 μmol/L substrate concentration,under varying substrate conditions.The fluo-rescent substrate assay demonstrated more significant intergroup differences than the chemical chromogenic substrate assay when various inhibitors were added.This study established a fluorescence-based enzyme activity assay for leucyl aminopeptidase from Echinococcus multilocularis by using Leu-AMC as the substrate;this method demonstrated a more significant intergroup difference and sensitivity than the chemical chromogenic substrate assay.

Aim To investigate the mechanism of in-testinal mucosal barrier protective effect of Qingjie Huagong decoction(QJHGD)on rats with severe acute pancreatitis(SAP).Methods The SAP rat model was constructed,and the sham-operation group,the model group,the group administered with different dosages of QJHGD,and the positive control group were set up respectively.HE staining was used to observe the histopathological changes.ELISA was employed to detect the serum levels of diamine oxidase(DAO)and D-lactic acid(D-LA)in rats.Transmission electron microscopy was utilized to observe the mitochondria of ileal tissues.qRT-PCR and Western blot were applied to detect the mRNA and protein expression of PGAM5,Drp1,PINK1,Parkin,LC3B in ileal tissues of rats.Results Compared with the sham-operated group,the pancreas and ileum tissues of rats in the model group showed obvious pathological changes,with abnormal mitochondrial structure and reduced number of autoph-agic vesicles in the ileum tissues.The levels of DAO and D-LA in serum increased(P＜0.01),and the mRNA and protein expression of PGAM 5,Drp 1,PINK1,Parkin,and LC3B in the ileum tissues de-creased significantly.Compared with the model group,pancreatic and ileal pathology were improved,mito-chondrial damage in the ileum was reduced,and the number of autophagic vesicles increased in the QJHGD group.The serum levels of DAO and D-LA were re-duced,and the expression of PGAM5,Drp1,PINK1,Parkin,and LC3B mRNA and protein in the ileal tis-sues increased significantly.Conclusions QJHGD may exert a protective effect on the SAP intestinal mu-cosal barrier by regulating the PGAM5/Drp1/PINK1/Parkin axis in order to elevate the level of mitochondri-al autophagy in the intestinal epithelial cells,thereby improving the level of repair of the intestinal epithelial cells.

Objective:To compare the efficacy of neuroendoscopy-assisted small bone window craniotomy and large bone flap craniotomy for acute subdural hematoma (ASDH) evacuation in elderly patients.Methods:A retrospective cohort study was conducted to analyze the clinical data of 57 elderly patients with ASDH admitted to Chongqing University Fuling Hospital from November 2020 to November 2023, including 27 males and 30 females, aged 65-89 years [(75.0±7.0)years]. The preoperative Glasgow coma scale (GCS) ranged 8-15 points [11.0(11.0, 12.0)points]. Among them, 27 patients were treated with neuroendoscopy-assisted small bone window craniotomy to evacuate ASDH (small bone window group) and 30 received large bone flap craniotomy to evacuate ASDH (large bone flap group). The following parameters were compared between the two groups: surgical duration, intraoperative blood loss, and length of hospital stay; residual subdural hematoma volume before surgery and at 1 day after surgery; GCS before surgery, at 1 and 3 days after surgery; good rate of Glasgow outcome scale (GOS) at 7 days and 6 months after surgery; and postoperative complication rate.Results:All the patients were followed up for 6 months. The surgical duration, intraoperative blood loss, and length of hospital stay were 89.0(85.0, 96.0)minutes, 65.0(55.0, 85.0)ml, and 15.0(14.0, 16.0)days, respectively in the small bone window group, which were shorter or less than 135.0(127.5, 150.0)minutes, 332.0(308.0, 367.5)ml, and 18.5(16.0, 20.0)days in the large bone flap group ( P<0.01). There was no statistically significant difference in the residual subdural hematoma volume between the two groups before surgery and at 1 day after surgery ( P>0.05). No statistically significant difference was found in GCS scores between the two groups before surgery ( P>0.05), while the GCS scores in the small bone window group at 1 and 3 days after surgery [12.0(12.0, 13.0)points and 15.0(14.0, 15.0)points] were higher than 11.5(11.0, 12.0)points and 13.0(12.8, 14.0)points in the large bone flap group ( P<0.01). The good rate of GOS in the small bone window group at 7 days after surgery was 100% (27/27), higher than 77% (23/30) in the large bone flap group ( P<0.05), but no statistically significant difference was found in the good rate of GOS between the two groups at 6 months after surgery ( P>0.05). Two patients in the small bone window group had pulmonary infection after surgery, with a complication rate of 7% (2/27), while in the large bone flap group, four patients had pulmonary infection, two epidural hematoma, one intracranial infection, one delayed wound healing, one subcutaneous fluid accumulation, and one epilepsy after surgery, with a complication rate of 33% (10/30) ( P<0.05). Conclusion:Compared with the conventional large bone flap craniotomy, neuroendoscopy-assisted small bone window craniotomy can shorten the surgical duration and length of hospital stay, reduce the intraoperative bleeding volume, promote early functional recovery, improve prognosis, and reduce the complication rate in elderly patients with ASDH.

The integration of science and education is not only an important strategy for promoting social progress and technological development,but also a modern form of higher education aiming at cultivating innovative talents.Conducting scientific research training for undergraduate medical students is one of the important ways to cultivate their innovative abilities and comprehensive qualities.Our team proposed a"teaching,science,and ideology trinity"teaching model to comprehensively cultivate students' scientific research comprehensive abilities under the value orientation of ideological and political education by or-ganically integrating molecular biology experimental teaching with the scientific research training of under-graduate medical students.In this teaching activity,taking the experiment of gene polymorphism as an example,our team selected students with research potential from the whole grade and divided them into 4 project groups that were instructed by 4 teachers.The students were trained in the whole process of scien-tific research,including topic selection,project writing,experimental designing,application for research ethics,and project summary.Our team has always adhered to student-contentedness of educational con-cepts to stimulate students' intrinsic motivation throughout the teaching process.Students are the design-ers and implementers of the project,and teachers are only guides and promoters of learning.After this training,students not only became familiar with the writing and implementation of scientific research pro-jects,but also improved their literature reading,experimental designing,experimental skills,and prob-lem-solving abilities.More importantly,this teaching activity also cultivated students' awareness of re-search ethics and academic moral standards.

Methodological quality assessment is a pivotal link between primary studies and reliable evidence-based practice,and an essential pathway for operationalizing the core principles of the Guide on Methodological Standards in Pharmacoepidemiology(2nd edition).A prevalent challenge in practice,however,is the conflation of appraising methodological robustness(risk of bias assessment)with verifying reporting transparency(adherence to reporting guidelines).This paper systematically addresses this fundamental challenge,beginning with a clear distinction between the essence and boundaries of these two concepts.On this basis,the article provides a comprehensive review of mainstream quality assessment tools,covering the methodological features and evolutionary trajectory of numerous instruments for interventional(e.g.,RoB 2,ROBINS-I),observational(e.g.,NOS,the JBI/SIGN/NIH series),secondary(e.g.,AMSTAR 2),and other specific types of studies such as health economic evaluations.Furthermore,a complete case study is used to illustrate the practical application of the ROBINS-I tool.The paper's central thesis advocates for an"appraisal-informed design"philosophy,urging a conceptual shift from the retrospective critique of existing literature to the prospective quality control of new research by internalizing appraisal standards as design principles,while also exploring the emerging paradigm of artificial intelligence in assisting assessment.This paper provides a comprehensive methodological reference for researchers and practitioners to prudently select appropriate assessment tools and to conduct rigorous critical appraisals of pharmacoepidemiological evidence.

Aim To explore the therapeutic effect and mechanism of Qingjie Huagong decoction in modulating PI3K/AKT/NF-κB signaling pathway in inflammatory response of acute pancreatitis(AP)mice.Methods Twenty-four mice were randomly divided into Blank group,Model group,Ustekin group,and Qingjie Hua-gong decoction group,with six mice in each group.The AP model was prepared by using rain frogin.Serum α-AMS,PNLP,IL-1β,IL-6,IL-8,IL-18,and TNF-α lev-els were detected by ELISA;the pancreatic pathology was detected by HE staining;the expressions of PI3K,AKT,and NF-κB-related proteins and mRNAs were de-tected by immunohistochemistry,Western blot,and RT-qPCR.Results Compared with the blank group,the model group showed obvious pathological damage to the pancreas,with significantly higher serum α-AMS,PN-LP,IL-1β,IL-6,IL-8,IL-18,and TNF-α levels(P＜0.01),and significantly higher levels of PI3K,AKT,and NF-κB-related proteins and mRNA expression(P＜0.01).Compared with the model group,both the Qingjie Huagong decoction group and the ustekin group improved the histopathological changes in the pancreas of AP mice,decreased the serum α-AMS,PNLP,IL-1β,IL-6,IL-8,IL-18,and TNF-α levels,and down-reg-ulated the expression levels of pancreatic PI3K,AKT,NF-κB-related proteins and mRNA(P＜0.05 or P＜0.01).Conclusion Qingjie Huagong decoction may inhibit the inflammatory response and protect pancreat-ic tissues by regulating the expression of PI3K/AKT/NF-κB signaling pathway.

Objective To investigate the incidence and types of patient-ventilator asynchrony(PVA)in mechanically ventilated patients within the intensive care unit(ICU),and to identify associated high-risk factors,thereby providing a basis for reducing PVA,enhancing mechanical ventilation efficiency,and refining ventilation strategies.Methods A prospective observational study was conducted among patients admitted to the general ICU of the Affiliated Hospital of Guizhou Medical University from October to December 2024 who were receiving mechanical ventilation.Inclusion criteria were as follows:age ≥18 years and mechanical ventilation duration ≥12 hours.Exclusion criteria included complete controlled mechanical ventilation,palliative care or do-not-resuscitate status,and lack of informed consent.Senior respiratory therapists performed daily bedside observations of ventilator waveforms for 10～15 minutes between 08:00 and 12:00.PVA was diagnosed based on pressure-time and flow-time waveforms,with the types of PVA being recorded.Demographic and clinical data,including age,sex,body mass index(BMI),primary diagnosis,comorbidities,APACHEⅡ score at ICU admission,blood gas analysis,ventila-tion mode and parameters,analgesia and sedation status,duration of mechanical ventilation,and length of ICU stay,were collected.The incidence and types of PVA during the observation period were analyzed.Univariate and multivariate logistic regression analyses were performed to identify high-risk factors for PVA.Clinical outcomes were compared between patients with and without PVA.Results A total of 105 patients and 453 episodes of assisted mechanical ventilation waveforms were analyzed.Among these,60.95％(64/105)experienced at least one episode of PVA.Of the 453 ventilation waveforms assessed,35.76％(162/453)demonstrated PVA.The types of PVA,ranked by incidence,were as follows:cycling mismatch(12.58％,57/453),double triggering(11.92％,54/453),ineffective triggering(9.49％,43/453),flow starvation(5.30％,24/453),and exhalation flow limitation(1.77％,8/453).The incidence of PVA varied significantly across different ventilation modes:45.7％in volume-assist/control ventilation(V-A/C),38.1％in pressure-assist/control ventilation(P-A/C),42.9％in synchronized intermittent mandatory ventilation(SIMV),and 16.7％in pressure support ventilation(PSV)(P<0.001).Multi-variate logistic regression analysis revealed that the mechanical ventilation mode[reference:PSV;V-A/C:OR=4.687,95％CI:2.140～10.263,P<0.001;P-A/C:OR=2.922,95％CI:1.489～5.734,P=0.002;SIMV:OR=4.682,95％CI:1.758～12.466,P=0.002]and actual respiratory rate(OR=1.07,95％CI:1.016～1.127,P=0.011)were significant high-risk factors for PVA.Patients with PVA had a significantly longer duration of mechanical ventilation[8.21(5.35,13.91)days vs.3.00(1.96,5.71)days,P<0.001]compared to those without PVA.Conclusions PVA is commonly observed in ICU patients receiving assisted invasive mechanical ventilation,with cycling mismatch,double triggering,and ineffective triggering being the most prevalent types.The incidence of PVA tends to be lower when using the PSV mode.Clinically,real-time monitoring of patient-ventilator synchrony via ventilator waveforms,along with the optimization of ventilator modes and parameters,should be employed to minimize the occurrence of PVA and enhance the efficiency of mechanical ventilation.

The integration of science and education is not only an important strategy for promoting social progress and technological development,but also a modern form of higher education aiming at cultivating innovative talents.Conducting scientific research training for undergraduate medical students is one of the important ways to cultivate their innovative abilities and comprehensive qualities.Our team proposed a"teaching,science,and ideology trinity"teaching model to comprehensively cultivate students' scientific research comprehensive abilities under the value orientation of ideological and political education by or-ganically integrating molecular biology experimental teaching with the scientific research training of under-graduate medical students.In this teaching activity,taking the experiment of gene polymorphism as an example,our team selected students with research potential from the whole grade and divided them into 4 project groups that were instructed by 4 teachers.The students were trained in the whole process of scien-tific research,including topic selection,project writing,experimental designing,application for research ethics,and project summary.Our team has always adhered to student-contentedness of educational con-cepts to stimulate students' intrinsic motivation throughout the teaching process.Students are the design-ers and implementers of the project,and teachers are only guides and promoters of learning.After this training,students not only became familiar with the writing and implementation of scientific research pro-jects,but also improved their literature reading,experimental designing,experimental skills,and prob-lem-solving abilities.More importantly,this teaching activity also cultivated students' awareness of re-search ethics and academic moral standards.

Objective:To compare the efficacy of neuroendoscopy-assisted small bone window craniotomy and large bone flap craniotomy for acute subdural hematoma (ASDH) evacuation in elderly patients.Methods:A retrospective cohort study was conducted to analyze the clinical data of 57 elderly patients with ASDH admitted to Chongqing University Fuling Hospital from November 2020 to November 2023, including 27 males and 30 females, aged 65-89 years [(75.0±7.0)years]. The preoperative Glasgow coma scale (GCS) ranged 8-15 points [11.0(11.0, 12.0)points]. Among them, 27 patients were treated with neuroendoscopy-assisted small bone window craniotomy to evacuate ASDH (small bone window group) and 30 received large bone flap craniotomy to evacuate ASDH (large bone flap group). The following parameters were compared between the two groups: surgical duration, intraoperative blood loss, and length of hospital stay; residual subdural hematoma volume before surgery and at 1 day after surgery; GCS before surgery, at 1 and 3 days after surgery; good rate of Glasgow outcome scale (GOS) at 7 days and 6 months after surgery; and postoperative complication rate.Results:All the patients were followed up for 6 months. The surgical duration, intraoperative blood loss, and length of hospital stay were 89.0(85.0, 96.0)minutes, 65.0(55.0, 85.0)ml, and 15.0(14.0, 16.0)days, respectively in the small bone window group, which were shorter or less than 135.0(127.5, 150.0)minutes, 332.0(308.0, 367.5)ml, and 18.5(16.0, 20.0)days in the large bone flap group ( P<0.01). There was no statistically significant difference in the residual subdural hematoma volume between the two groups before surgery and at 1 day after surgery ( P>0.05). No statistically significant difference was found in GCS scores between the two groups before surgery ( P>0.05), while the GCS scores in the small bone window group at 1 and 3 days after surgery [12.0(12.0, 13.0)points and 15.0(14.0, 15.0)points] were higher than 11.5(11.0, 12.0)points and 13.0(12.8, 14.0)points in the large bone flap group ( P<0.01). The good rate of GOS in the small bone window group at 7 days after surgery was 100% (27/27), higher than 77% (23/30) in the large bone flap group ( P<0.05), but no statistically significant difference was found in the good rate of GOS between the two groups at 6 months after surgery ( P>0.05). Two patients in the small bone window group had pulmonary infection after surgery, with a complication rate of 7% (2/27), while in the large bone flap group, four patients had pulmonary infection, two epidural hematoma, one intracranial infection, one delayed wound healing, one subcutaneous fluid accumulation, and one epilepsy after surgery, with a complication rate of 33% (10/30) ( P<0.05). Conclusion:Compared with the conventional large bone flap craniotomy, neuroendoscopy-assisted small bone window craniotomy can shorten the surgical duration and length of hospital stay, reduce the intraoperative bleeding volume, promote early functional recovery, improve prognosis, and reduce the complication rate in elderly patients with ASDH.