ObjectiveThis study aimed to establish a monocrotaline （MCT）-induced pulmonary arterial hypertension （PAH） rat model to systematically evaluate the protective effect of Xiao Qinglongtang （XQLT） on right cardiac function in model rats and further elucidate the underlying regulatory mechanism. MethodsSixty male SD rats were randomly assigned to the normal group， model group， XQLT low-， medium-， and high-dose groups （XQLT-L/M/H）， and the beraprost sodium tablet group （BST）. Except for the normal group， rats in all other groups were given a single subcutaneous injection of MCT （60 mg·kg^-1） to induce PAH. Three weeks after injection， rats in the XQLT-L/M/H groups were administered XQLT intragastrically at 3.07， 6.14， 12.28 g·kg^-1·d^-1， respectively. Rats in the BST group received beraprost sodium at 12.6 μg·kg^-1·d^-1， and rats in the model group received an equal volume of saline. All treatments lasted for 3 weeks. Right ventricular systolic pressure （RVSP） was measured by right ventricular catheterization. Cardiac function was assessed by echocardiography. The right ventricle was weighed to calculate the right ventricular hypertrophy index （RVHI）. Hematoxylin-eosin （HE） staining， Masson staining， and transmission electron microscopy were used to observe myocardial morphology. Serum metabolomic changes were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS）. Data-independent acquisition （DIA） proteomics was used to detect differentially expressed （DE） proteins in the right ventricle， and Western blot was used to measure the expression of uncoupling protein 3 （UCP3）， phosphatidylinositol 3-kinase catalytic subunit p110α （PIK3CA）， L1 cell adhesion molecule （L1CAM）， and quinone oxidoreductase （CRYZ）. UPLC-MS/MS was used to analyze the chemical components of XQLT. ResultsCompared with the normal group， the model group showed significantly increased RVSP and RVHI （P<0.05）， along with pathological changes in myocardial morphology. Compared with the model group， all XQLT-treated groups exhibited reductions in RVSP and RVHI as well as significant improvements in cardiac function and myocardial morphology. Among the XQLT groups， XQLT-M showed the most pronounced effects （P<0.05）， comparable to the BST group. Serum metabolomics revealed 105 differential metabolites in the XQLT groups versus the model group ［variable importance in projection （VIP） >1， P<0.05］， including 58 upregulated and 47 downregulated metabolites. KEGG enrichment analysis indicated that XQLT intervention downregulated phenylalanine metabolism （P<0.01） and upregulated unsaturated fatty acid biosynthesis （P<0.05）. Proteomics analysis showed that 982 DE proteins were identified in the MCT groups versus the normal group， including 455 upregulated and 527 downregulated proteins （|fold change （FC）| >1.3， P<0.05）. Compared with the model group， 237 DE proteins were identified in the XQLT groups， including 124 upregulated and 113 downregulated proteins （|FC| >1.3， P<0.05）， with 57 overlapping DE proteins. KEGG enrichment suggested that XQLT mainly modulated pathways related to mineral absorption， ribosomal biogenesis， peroxisomes， glycolysis/gluconeogenesis， spliceosomes， and thyroid hormone signaling. Western blot analysis showed that， compared with the model group， XQLT increased the expression of UCP3， PIK3CA， and L1CAM， while decreasing the expression of CRYZ （P<0.05）. ConclusionXQLT exerts a protective effect on right heart function in MCT-induced PAH rats， and its mechanism is associated with maintaining myocardial homeostasis and alleviating right ventricular remodeling.

To evaluate the application value of the Peyton four-step teaching method in the standardized training of intestinal ultrasound and compare it with traditional teaching methods, so as to provide an optimized approach for clinical ultrasound training.

To investigate the effectiveness of a teaching model combining real-case bedside instruction with mixed-level group teaching in intestinal ultrasound training, and to provide reference forestablishing an efficient and practical training system for intestinal ultrasound.

AIM To observe the protective effects and mechanism of Shuli Jiangzhuo Formula on cardiac function in a rat model of uremic cardiomyopathy(UCM).METHODS The successful UCM models established by 5/6 nephrectomy were randomly allocated into the model group,the valsartan group(8.33 mg/kg),and the low-dose,medium-dose and high-dose Shuli Jiangzhuo Formula groups(7.19,14.38,28.76 g/kg),in contrast to those of the sham operation group,followed by 8 weeks respective drug administration.Upon the completion of the pharmacological intervention,the rats had the left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),ejection fraction(EF)and fractional shortening(FS)measured by echocardiography;the whole heart mass index(HMI)and left ventricular mass index(LVMI)detected;the renal function(serum creatinine,blood urea nitrogen)and the hemoglobin concentration detected;the mitochondrial morphology analyzed by observation of cardiomyocyte ultrastructure using transmission electron microscopy;the DNA damage in cardiomyocytes detected by TUNEL staining;the serum levels of IL-1β,IL-18 and BNP detected by ELISA;and the myocardial mRNA and protein expressions of NLRP3,Caspase-1 and IL-1β detected by RT-qPCR and Western blot.RESULTS Compared with the sham operated controls,the model group demonstrated significant elevation of serum creatinine and urea nitrogen(P＜0.01);decreased hemoglobin concentration(P＜0.01);disorganized myocardial collagen fiber architecture,and pronounced mitochondrial swelling with ultrastructural damage;decreased EF and FS(P＜0.05);increased LVEDD and LVESD(P＜0.01);increased HMI and LVMI(P＜0.01);increased levels of serum IL-1β,IL-18 and BNP(P＜0.01);increased cardiomyocyte pyroptosis(P＜0.01);and enhanced mRNA and protein expressions of NLRP3,Caspase-1 and IL-1 β(P＜0.01).Compared to model group controls,the high-dose Shuli Jiantuo Formula intervention exhibited decreased levels of serum creatinine and urea nitrogen(P＜0.01);increased hemoglobin concentration(P＜0.01);reduced DNA fragmentation,alleviated mitochondrial swelling and mitigated ultrastructural damage;reduced LVEDD and LVESD(P＜0.05,P＜0.01);decreased HMI and LVMI(P＜0.01);downregulated levels of serum IL-1β,IL-18 and BNP(P＜0.01);decreased cardiomyocyte pyroptosis(P＜0.01);and inhibited mRNA and protein expressions of NLRP3,Caspase-1 and IL-1β(P＜0.05,P＜0.01).CONCLUSION Shuli Jiangzhuo Formula demonstrates dual cardiorenal protective effects in UCM rats through suppression of the left ventricular hypertrophy progression and inhibition of the adverse ventricular remodeling processess.The therapeutic efficacy primarily stems from targeted suppression of NLRP3/Caspase-1 signaling pathway activation and substantial attenuation of cardiomyocyte pyroptosis cascade.

Objective:To detect the association of tumor circumferential involvement range (CIR) with neoadjuvant chemoradiotherapy (NCRT) efficacy and long-term survival outcomes in locally advanced rectal cancer (LARC) patients.Methods:Clinical data of 451 patients admitted to our hospital from January, 2018 to January, 2022 were retrospectively collected. According to the CIRs as determined by rectal magnetic resonance imaging, patients were divided into the High group (≥2/3 cycle, 270 patients) and the Low group (＜2/3 cycle, 181 patients). The primary outcome was three-year disease-free survival. The baseline characteristics, pathological features, and survival outcomes were compared.Results:Compared to patients in the Low group, patients in the High group exhibited significantly larger tumor vertical diameters [(4.7±1.7) vs. (3.6±1.4)cm, P＜0.001], higher rates of mrT4 stage (37.8% vs. 13.2%, P＜0.001), and higher rates of positive mesorectal fascia (54.1% vs. 29.8%, P＜0.001) and extramural vascular invasion (55.6% vs. 38.1%, P＜0.001). Patients in the High group were mainly pT3-4 stages (46.7% vs. 30.9%, P=0.002), with significantly lower rates of pathological complete response (22.2% vs. 33.1%, P=0.010) , poorer tumor regression grades (48.9% vs. 60.8%, P=0.013), and higher rates of positive peripheral nerve invasion (11.5% vs. 5.5%, P=0.031), as compared to patients in the Low group. The median follow-up time was 40 months. About 11 (2.4%) and 48 patients (10.6%) experienced tumor local recurrence and distant metastasis, respectively. The recurrence rates were 2.2% and 2.6%, and the distant metastasis rates were 7.7% and 12.6%, respectively, in the Low group and the High group, with no statistical significance ( P=0.957, P=0.096). The three-year disease-free survival in the High group was significantly lower than that in the Low group (84.4% vs. 92.4%, P=0.014). Conclusions:The CIR is closely related to tumor burden, which can judge tumor response to NCRT, and is negatively related to survival prognosis. For patients who have more than a 2/3 cycle of CIR, intensified or consolidated treatments may be required to improve survival outcomes.

Objective:To establish a mouse model of liver cancer resistant to PD-1 monoclonal antibody and analyze the changes in its metabolomics to explore the potential mechanism of drug resistance.Methods:BALB/c mice were randomly divided into control and treatment groups after being loaded with tumor,and a normal group was additionally set up.The normal and control groups were injected with saline,and the treatment group was injected with PD-1 monoclonal antibody,after which the mice in the treatment group were screened for drug resistant and response groups.Observed the drug-resistant situation,body mass,tumor growth and survival rate of mice in each group,calculate the spleen index.The pathological features of tumor tissues were observed by HE staining method.Serum metabolites were detected by non-targeted metabolomics.Finally,a bivariate Pearson correlation analysis was conducted between the differential serum metabolites and tumor size.Results:The tumor-bearing mouse model with PD-1 monoclonal antibody resistance was successfully established,and the drug resistance rate of the mice was 50％.Compared with the normal and response groups,mice in the resistant group showed an increase in body weight,a significant increase in tumor volume,a decrease in survival rate,and a significant increase in splenic index.There was less lymphocyte infiltration in the tumor tissue.Metabolomics analysis showed that the serum levels of glutamic acid and aspartic acid increased and malic acid decreased in the resistant mice compared with the response group,and these changes were closely related to the arginine biosynthesis pathway.Conclusions:The tumor-bearing mouse model with PD-1 monoclonal antibody resistance was successfully established.The changes in its peripheral serum metabolomics mainly involve arginine metabolism and the related changes of aspartate,malate and glutamate.

Aim To investigate the role of RNF8 in the proliferation,invasion and migration of hepatocellular carcinoma and in the promotion of epithelial-mesenchy-mal transition(EMT);to clarify the regulatory mecha-nism of RNF8 on hepatocellular carcinoma cells.Methods Immunohistochemistry was used to detect the expression of RNF8 and RhoA in human hepatocel-lular carcinoma tissues and adjacent tissues;Western blot and RT-PCR were used to detect the expression levels of RNF8 and RhoA in human normal hepatocytes and hepatocellular carcinoma cells.RNF8 was overex-pressed in HepG2 cells,and siRNA interference was used to downregulate the expression of RNF8.The cell experimental groups were as follows:control group(Control,normal HepG2 cells),RNF8 overexpression group,RNF8 low expression group(siRNA RNF8),RNF8 overexpression+Rhosin(20 μmol·L-1,RhoA blocker)group.The cell proliferation ability was detected by CCK-8 method;the cell migration ability was detected by scratch test;the cell invasion ability was detected by Transwell test;finally,the expression levels of RNF8,RhoA,PCNA,CyclinD1,N-cadherin,vimentin,Slug,and E-cadherin proteins and mRNA were detected by Western blot and RT-PCR.Results The expression of RNF8 and RhoA in liver cancer tissues and liver cancer cells significantly increased;after RNF8 knockdown,the proliferation,migration,in-vasion and EMT of liver cancer cells were significantly inhibited,while overexpression of RNF8 significantly increased the proliferation,migration,invasion ability of liver cancer cells and promoted EMT.RhoA showed a positive correlation with knockdown and overexpression of RNF8.When RNF8 was overexpressed and RhoA blocker was given at the same time,the phenomenon of overexpression of RNF8 increasing the proliferation,mi-gration,invasion ability and promoting EMT of liver cancer cells was significantly reversed.Conclusions RNF8 can promote the proliferation,migration,invasion and EMT of liver cancer cells,and at the same time promote the expression of RhoA.RNF8 promotes the progression of hepatocellular carcinoma by regulating RhoA to promote EMT.

Objective To investigate the effect and mechanism of methyl oxofulnonone A(META)on high glucose(HG)-induced H9c2 cell injury.Methods H9c2 cells were divided into control group(normal culture),model group(55 mmol·L-1 glucose)and experimental-L,-M,-H groups(55 mmol·L-1 glucose+12.5,25.0,50.0 μmol·L-1 META).Cell viability was detected by cell counting kit-8;intracellular reactive oxygen species(ROS)level was detected by DCFH-DA fluorescent probe;intracellular adenosine triphosphate(ATP)content was detected by luciferase;and autophagy-related protein expression was detected by Western blotting.Results The optical density values of 72-hour cells in the control group,model group and experimental-M,-H groups were 0.91±0.03,0.61±0.01,0.69±0.02 and 0.72±0.03;the ROS levels were(40.75±1.53)％,(43.73±1.30)％,(30.87±1.27)％and(28.28±1.43)％;the ATP contents were(8.16±0.71),(4.03±0.29),(5.29±0.31)and(5.83±0.31)nmol·mg-1;the relative expression levels of autophagy-related gene 5 protein were 1.05±0.06,1.46±0.09,0.98±0.11 and 0.89±0.09;the relative expression levels of ubiquitin-binding protein were 1.05±0.10,0.55±0.13,0.89±0.04 and 0.98±0.04;the ratios of microtubule-associated protein 1 light chain 3 11/Ⅰ protein were 1.09±0.09,1.82±0.05,1.67±0.29 and 1.09±0.15,respectively.Among the above indicators,there were statistically significant differences between the model group and the control and experimental-M,-H groups(P＜0.05,P＜0.01).Conclusion META significantly ameliorates H9c2 cardiomyocyte damage caused by high glucose,ameliorates oxidative stress,protects mitochondrial respiration and inhibits autophagy.

Objective:To compare the prognostic impact of complete mesocolic excision (CME) versus D2 lymphadenectomy in patients with stage III right-sided colon cancer.Methods:A retrospective cohort study was conducted. Clinical data of 263 patients with stage III colon cancer undergoing right hemicolectomy in the Division of Colorectal Surgery, Department of General Surgery, Peking Union Medical College Hospital (January 1, 2016 to August 8, 2023) were included. Of the 263 patients, 152 underwent CME and 111 received D2 dissection. Propensity score matching (PSM) was employed to balance baseline characteristics between the two groups. Continuous variables were compared using the Mann-Whitney U test or Student's t-test; categorical variables were compared using the χ2 test or Fisher exact test. Survival curves were constructed using the Kaplan-Meier method, and the Log-Rank test was used to compare disease-free survival (DFS) and overall survival (OS) between groups. Cox proportional hazards models were utilized to analyze prognostic factors, with subgroup analyses performed.Results:Patients undergoing CME surgery were younger (proportion >75 years: 4.6% vs. 25.2%, P<0.001), had a lower burden of comorbidities (Charlson comorbidity index ≥ 1: 25.0% vs. 36.9%, P=0.045), The rates of open surgery and converted open surgery were lower [0.6% (1/152) vs. 4.5% (5/111) and 0.6% (1/152) vs. 2.7% (3/111), respectively; P=0.040].They also had a higher rate of receiving adjuvant therapy (92.7% vs. 76.0%, P<0.001). In terms of short-term postoperative outcomes, the CME group had a greater number of harvested lymph nodes (median: 30 vs. 25, P<0.001) and less blood loss (median: 20 ml vs. 20 ml, P=0.041). There were no significant differences between the groups in terms of the number of metastatic lymph nodes, operation time, and the incidence of postoperative complications. Survival analysis demonstrated significantly longer DFS in the CME group both before and after PSM. CME was an independent favorable prognostic factor for DFS (pre-PSM: HR=0.53, 95%CI: 0.31-0.91, P=0.022; post-PSM: HR=0.50, 95%CI: 0.26-0.97, P=0.042). No significant difference in OS was detected between the two groups across models. The subgroup analysis based on clinicopathological features revealed DFS benefits associated with CME in patients with tumor deposits (HR=0.41, 95%CI: 0.18-0.94, P=0.035), moderately-to-well-differentiated adenocarcinoma(HR=0.48, 95%CI: 0.26-0.90, P=0.023), proficient mismatch repair tumors (HR=0.55, 95%CI: 0.32-0.94, P=0.030), and pN2 stage disease (HR=0.43, 95%CI: 0.19-0.95, P=0.036). Conclusion:An extended lymph node dissection, as exemplified by CME, may confer a DFS advantage in patients with stage III right-sided colon cancer, especially those exhibiting a substantial burden of lymph node metastases.

Objective:To analyze the clinical characteristics of pulmonary mucormycosis (PM) in children with leukemia, and explore its diagnosis and treatment strategies and prognosis.Methods:In this case-series study, the clinical data of 19 children who were diagnosed with leukemia complicated by PM at the First Affiliated Hospital of Zhengzhou University from January 2020 to June 2024 were retrospectively analyzed.Their gender, age, type of leukemia, clinical manifestations, chest CT findings, bronchoscopy results, etiology, treatment regimens, and prognosis were summarized.The patients were divided into a survival group and a death group.The clinical data were compared between the 2 groups.Categorical variables were compared using the Fisher′s exact test, and continuous variables were compared using the Wilcoxon rank-sum test.Results:A total of 19 children aged 2 to 17 years with leukemia complicated by PM were involved, including 9 boys and 10 girls, with most cases (15 cases) occurring in the autumn and winter.The median time from the first leukemia chemotherapy to infection with mucor was 1 month.Clinical manifestations mainly included fever (100%), cough (94.7%), hemoptysis (42.1%), and pneumothorax (21.1%).Chest CT findings primarily showed extensive lung consolidation (84.2%), pleural effusion (84.2%), pulmonary nodules (78.9%), halo signs (73.7%), cavitation (36.8%), crescent signs (26.3%), and reverse halo signs (21.1%).Fourteen children underwent bronchoscopy, which primarily revealed tracheal obstruction, pale or congested mucosa, mucosal edema, mucosal necrosis, bronchial stenosis, and bronchial cavitary fistulas.Mucor was detected using various methods including metagenomic next-generation sequencing (mNGS), cultures, and lung tissue microscopy.Patients were mainly treated with intravenous administration of Amphotericin B in different formulations combined with oral Posaconazole.Three patients also underwent surgical resection of the affected lung lobe in addition to medical treatment.After treatment, 14 patients had a good prognosis, while 5 patients died.The causes of death were massive hemoptysis in 2 cases, severe respiratory failure in 1 case, and treatment withdrawn due to critical condition in 2 cases.There were no statistically significant differences in age, gender, type of leukemia, whether to undergo bronchoscopy and surgery, time from the first chemotherapy to onset of infection, presence of comorbid infection, chest CT characteristics, and time to start treatment between survival and death groups(all P>0.05). Conclusions:There is no specificity in clinical manifestations of leukemia complicated by PM, which, however, still exhibits some characteristics.mNGS plays a crucial role in early diagnosis.Intravenous administration of Amphotericin B combined with oral Posaconazole and surgical intervention are an effective treatment regimen.