OBJECTIVE To retrospectively analyze the drug resistance characteristics of the patients with multidrug-resistant organisms(MDROs)infections who were hospitalized from 2022 to 2023 and observe the effect of multi-disciplinary teamwork(MDT)mode so as to provide scientific bases for prevention and control of MDROs infec-tions and hospital-associated infections.METHODS A total of 639 patients with MDROs infection who were hospi-talized in Jianyang People's Hospital from Jan.2022 to Dec.2023 were recruited as the research subjects.The clinical data were collected from the patients,the drug resistance characteristics of bacteria were analyzed.The effects of MDT and pharmacological supervision on treatment of the patients with MDROs infection were observed and compared.RESULTS The methicillin-resistant Staphylococcus aureus(MRSA)(359 strains,56.18％)was dominant among the pathogens isolated from the 639 patients with MDROs infections,followed by the carbapen-em-resistant Klebsiella pneumoniae(CRKP)(96 strains,15.02％)and carbapenem-resistant Acinetobacter bau-mannii(82 strains,12.83％).Of the patients with MDROs infection,150(23.47％)were from critical care medicine department,94(14.71％)from pediatrics department,and 82(12.83％)from general surgery de-partment.The result of drug susceptibility test showed that the S.aureus strains were susceptible to linezolid,daptomycin,vancomycin and tigecycline;most of the gram-negative bacteria were susceptible to carbapenems,while the A.baumannii strains were highly resistant to the commonly used antibiotics.The total isolation rate of MDROs and the case-time infection rate of MDROs infections were 14.32％and 0.05％,respectively,after MDT and pharmacological supervision were carried out,lower than those before carried out;the effective treatment rate of the patients with MDROs was 76.47％after MDT and pharmacological supervision were carried out,higher than that before they were carried out,and there were significant differences(all P＜0.05).CONCLUSION MDT and pharmacological supervision may improve the curative effect of the patients with MDROs infection and reduce the isolation rate of MDROs as well as the incidence of hospital-associated infections.

OBJECTIVE To retrospectively analyze the drug resistance characteristics of the patients with multidrug-resistant organisms(MDROs)infections who were hospitalized from 2022 to 2023 and observe the effect of multi-disciplinary teamwork(MDT)mode so as to provide scientific bases for prevention and control of MDROs infec-tions and hospital-associated infections.METHODS A total of 639 patients with MDROs infection who were hospi-talized in Jianyang People's Hospital from Jan.2022 to Dec.2023 were recruited as the research subjects.The clinical data were collected from the patients,the drug resistance characteristics of bacteria were analyzed.The effects of MDT and pharmacological supervision on treatment of the patients with MDROs infection were observed and compared.RESULTS The methicillin-resistant Staphylococcus aureus(MRSA)(359 strains,56.18％)was dominant among the pathogens isolated from the 639 patients with MDROs infections,followed by the carbapen-em-resistant Klebsiella pneumoniae(CRKP)(96 strains,15.02％)and carbapenem-resistant Acinetobacter bau-mannii(82 strains,12.83％).Of the patients with MDROs infection,150(23.47％)were from critical care medicine department,94(14.71％)from pediatrics department,and 82(12.83％)from general surgery de-partment.The result of drug susceptibility test showed that the S.aureus strains were susceptible to linezolid,daptomycin,vancomycin and tigecycline;most of the gram-negative bacteria were susceptible to carbapenems,while the A.baumannii strains were highly resistant to the commonly used antibiotics.The total isolation rate of MDROs and the case-time infection rate of MDROs infections were 14.32％and 0.05％,respectively,after MDT and pharmacological supervision were carried out,lower than those before carried out;the effective treatment rate of the patients with MDROs was 76.47％after MDT and pharmacological supervision were carried out,higher than that before they were carried out,and there were significant differences(all P＜0.05).CONCLUSION MDT and pharmacological supervision may improve the curative effect of the patients with MDROs infection and reduce the isolation rate of MDROs as well as the incidence of hospital-associated infections.

Mannheimia varigena(M.varigena)is a significant pathogen causing bovine respiratory disease.Transferrin binding protein B(TbpB)is a lipoprotein directly exposed to the outer mem-brane of the cell,which is not only involved in the bacterial iron metabolism pathway,but also an important virulence factor.This study aims to lay the groundwork for developing novel subunit vaccines by conducting site-directed mutagenesis on M.varigena TbpB binding-related residues and evaluating their immunogenicity.Based on whole-genome sequencing of a bovine M.varigena i-solate,its iron uptake pathway was predicted.Key amino acid residues of M.varigena TbpB that play a role for binding to bovine transferrin(bTf)was identified by bioinformatics.We constructed two M.varigena TbpB mutants(Y205A and Y258A)and assessed their bTf binding activity and immunogenicity through dot blot assays and mouse immunization studies.Dot blot assays result showed that the Y258A mutation caused TbpB to lose its ability to bind to bTf.Mouse immuniza-tion studies showed that,compared to wild-type TbpB,the mutants of TbpB induced higher levels of specific antibodies.In challenge experiments,mice immunized with mutant TbpB exhibited high-er survival rates.These results demonstrate that site-directed mutagenesis can enhance the immu-nogenicity of TbpB.This study provides a novel approach for developing new subunit vaccines a-gainst M.varigena.

Objective To explore the therapeutic effect of precise disconnection of pargastric varices guided by endoscopic ultrasound in the treatment of esophagogastric variceal bleeding.Method A retrospective analysis was conducted on 20 patients with cirrhosis esophagogastric variceal bleeding treated with endoscopic ultrasound-guided precise disconnection of pargastric varices from January 1,2024 to December 31,2024.The efficacy was analyzed.Result All 20 patients successfully completed the precise disconnection of pargastric varices under the guidance of endoscopic ultrasound.The injection of tissue gel combined with the placement of spring coils(14 cases)and the injection of tissue gel alone(4 cases)successfully blocked the pargastric varices.All patients did not experience perforation,esophageal and cardia stenosis,massive bleeding,septicemia,or ectopic embolization.One patient who received tissue gel alone had slight bleeding from the pargastric varices after surgery and improved after 3 days of treatment to reduce portal vein pressure.Another one patient who received tissue gel alone had a low-grade fever and normal body temperature after 3 days of anti-infection treatment.Conclusion Precise disconnection of pargastric varices under the guidance of endoscopic ultrasound has a good therapeutic effect on esophagogastric variceal bleeding,with fewer complications such as ectopic embolization,massive bleeding,infection,and perforation.However,close follow-up observation is still needed to address the issue of pargastric varices.

Objective To explore the role of ferroptosis in DIC through bioinformatics analysis of hub genes involved in ferroptosis in doxorubicin-induced cardiomyopathy(DIC),combined with in vitro experimental validation.Methods Divalent iron fluorescence staining confirms the occurrence of ferroptosis in myocardial cells of DIC.The GSE207737 dataset was retrieved from the Gene Expression Comprehensive Database(GEO)and intersected with the FerrDb database to identify ferroptosis-related genes.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses of the intersected genes and intersecting the genes obtained from LASSO regression analysis and SVM-SFR machine learning methods were used to obtain ferroptosis hub genes for DIC.Real-time PCR was used to validate H9C2 cells in the control and DIC model groups,and Western blotting was used to further validate those whose bioinformatics and real-time PCR results that did not match.Results Thirty-eight ferroptosis-related genes in DIC were identified,and GO and KEGG analyses showed that these genes mainly participate in cell metabolism.Five hub genes for ferroptosis in DIC were obtained using machine learning methods:Mpc1,Prdx1,Kdm4a,Alox 12b,and Tfrc.Through in vitro experiments,the mRNA expression levels of Mpc1,Prdx1,and Kdm4a were downregulated in the DIC model group compared to those in the control group(P＜0.001),whereas the mRNA expression level of Alox12b was upregulated(P＜0.001).There were no significant differences in the mRNA or protein expression levels of Tfrc(P＞0.05).Conclusion Mpc1,Prdx1,Kdm4a,and Alox12b are key genes involved in ferroptosis in doxorubicin-induced cardiomyopathy and potential targets for the prevention and treatment of doxorubicin-induced cardiomyopathy in ferroptosis.

Chronic heart failure （CHF） is a complex clinical syndrome that the cardiac output is not enough to meet the metabolic needs of the body， or depends on the increase of filling pressure to compensate. Its high morbidity and mortality pose a serious threat to human health， necessitating attention and active intervention. At present， western medicine treatment of CHF is mainly based on diuretics， intravenous vasodilators， intravenous positive inotropic drugs， etc.， which， however， have problems such as long medication cycles， serious side effects， and limited applicable population. Recent studies have shown that traditional Chinese medicine can act in a multi-pathway， multi-component， and multi-target manner， showing unique advantages in the prevention and treatment of CHF. Buyang Huanwutang has the effects of tonifying Qi， activating blood， and dredging collaterals. Clinical and mechanism studies have confirmed that this prescription is effective in treating CHF and its syndromes. The clinical studies can be classified into two categories. Studies of the first category use simple modern medical diagnostic criteria as the inclusion criteria for CHF patients， which can improve the scientificity and objectivity. Studies of the second category uses modern medicine combined with traditional Chinese medicine disease diagnostic criteria for the screening of CHF patients， which helps to improve the accuracy of efficacy evaluation. However， there are problems such as the lack of unified research standards and the insufficiency of mechanism research. In addition， the available studies remain to be classified or summarized. This study systematically sorted out the clinical and mechanism studies of Buyang Huanwutang in the treatment of CHF in recent years to review the research status. In clinical treatment， Buyang Huanwutang can be used alone， or modified， or combined with other prescriptions or Western medicine. The mechanism studies predict that Buyang Huanwutang can ameliorate CHF by regulating the calcium balance， protecting the mitochondrial structure and function， and regulating intestinal flora. This review aims to provide a theoretical basis and practical guidance for the clinical application and optimization and subsequent in-depth study of Buyang Huanwutang in the treatment of CHF.

Mannheimia varigena(M.varigena)is a significant pathogen causing bovine respiratory disease.Transferrin binding protein B(TbpB)is a lipoprotein directly exposed to the outer mem-brane of the cell,which is not only involved in the bacterial iron metabolism pathway,but also an important virulence factor.This study aims to lay the groundwork for developing novel subunit vaccines by conducting site-directed mutagenesis on M.varigena TbpB binding-related residues and evaluating their immunogenicity.Based on whole-genome sequencing of a bovine M.varigena i-solate,its iron uptake pathway was predicted.Key amino acid residues of M.varigena TbpB that play a role for binding to bovine transferrin(bTf)was identified by bioinformatics.We constructed two M.varigena TbpB mutants(Y205A and Y258A)and assessed their bTf binding activity and immunogenicity through dot blot assays and mouse immunization studies.Dot blot assays result showed that the Y258A mutation caused TbpB to lose its ability to bind to bTf.Mouse immuniza-tion studies showed that,compared to wild-type TbpB,the mutants of TbpB induced higher levels of specific antibodies.In challenge experiments,mice immunized with mutant TbpB exhibited high-er survival rates.These results demonstrate that site-directed mutagenesis can enhance the immu-nogenicity of TbpB.This study provides a novel approach for developing new subunit vaccines a-gainst M.varigena.

Objective To analyze the effectiveness of the digital medicine boosting county-town-village linkage diabetes mellitus(DM)management model.Methods A total of 135 patients with T2DM from 9 villages in 3 towns of Longyou County from June to September 2021 were selected and randomly grouped into a control(Con,n=45)group and an intervention(Exp,n=90)group at a ratio of 1∶2 by village.The Con group implements routine management.The Exp group implemented the internet+boosting county-town-village linkage DM management model.Both groups were followed up for one year.The body mass index(BMI),waist circumference(WC),systolic blood pressure(SBP),diastolic blood pressure(DBP),fasting plasma glucose(FPG),hemoglobin A1c(HbA1c),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),triglycerides(TG),urine albumin/creatinine ratio(UACR),management compliance,and the proportion of new DM complications were compared between the two groups.Results All patients in the Con group completed follow-up,8 patients in the Exp group were lost to follow-up,and 82 patients were finally included.After the intervention,BMI,WC,SBP,DBP,FPG,HbA1c,TC,TG,LDL-C and UACR were significantly decreased in both groups(P<0.05),while HDL-C and DM self-management scale(SDSCA)scores increased(P<0.05).In Exp group,SBP,DBP,FPG,HbA1c,TC,TG,LDL-C and UACR were lower than those in Con group(P<0.05),while HDL-C and SDSCA scores and the compliance rates of FPG,HbA1c,TC,TG were higher than those in Con group(P<0.05).There was no statistically significant difference in the changes of medication methods,the incidence of diabetic kidney disease and diabetic peripheral neuropathy between the two groups(P>0.05).Conclusions The digital medicine boosting county-town-village linkage DM management model,which helps achieve glycolipid standards and opens up new ideas for the management of diabetes in rural areas.

Objective:To evaluate the outcomes of intensive conservative treatment compared to conventional conservative treatment in patients with acute aortic syndrome(AAS).Methods:The study prospectively enrolled consecutive patients with AAS who were admitted to Beijing Anzhen Hospital, affiliated with Capital Medical University, and Beijing Dawanglu Emergency Rescue Hospital from January 2024 to December 2024. These patients with surgical contraindications or refused surgery for various reasons opted for conservative treatment. A total of 282 patients were included, and 15 patients with missing data or those who died without any treatment were excluded. Finally, 267 patients were enrolled, of whom 94 received intensive conservative treatment, and 173 received conventional conservative treatment, the inverse probability of treatment weighting (IPTW) was used to reduce the influence of confoundings. After adjusting of baseline datas via IPTW, the survival outcomes of the two groups were compared at 14 days, 30 days, and at the end of follow-up.Results:The results showed significant differences in acute phase survival rates between the enhanced conservative treatment group and the conventional conservative treatment group at 14 days(82.40%vs.53.20%, P<0.0001). Significant survival differences were also observed at 30 days and at 276-day mid-term follow-up (96.29% vs.51.60%, P<0.0001; 78.50% vs.48.50%, P<0.0001). In the subgroup analysis, for type A aortic dissection, the enhanced conservative treatment group had higher survival rates compared to the conventional conservative treatment group at 14, 30 and 276 days (63.46% vs.41.35%, P<0.05; 52.17% vs.37.90%, P<0.05; 50.00% vs. 31.97%, P<0.05). However, for type B aortic dissection, although the enhanced conservative treatment group had higher survival rates than the conventional conservative treatment group, no statistically significant differences were observed (96.29% vs. 80.00%, P=0.054; 95.65% vs.78.37%, P=0.067; 94.12% vs.74.20%, P=0.088). Conclusion:For patients diagnosed with AAS are forced to choose conservative treatment if emergency surgery is not possible in the first place, intensive conservative treatment strategies can significantly reduce the mortality in the acute phase compared with conventional conservative treatment. Mid-term follow-up, intensive conservative treatment still has a significant survival advantage.

Ovarian cancer is the most lethal malignancy affecting the female reproductive system. Pharmacological inhibitors targeting CDK4/6 have demonstrated promising efficacy across various cancer types. However, their clinical benefits in ovarian cancer patients fall short of expectations, with only a subset of patients experiencing these advantageous effects. This study aims to provide further clinical and biological evidence for antineoplastic effects of a CDK4/6 inhibitor (TQB4616) in ovarian cancer and explore underlying mechanisms involved. Patient-derived ovarian cancer organoid models were established to evaluate the effectiveness of TQB3616. Potential key genes related to TQB3616 sensitivity were identified through RNA-seq analysis, and TRIM4 was selected as a candidate gene for further investigation. Subsequently, co-immunoprecipitation and GST pull-down assays confirmed that TRIM4 binds to hnRNPDL and promotes its ubiquitination through RING and B-box domains. RIP assay demonstrated that hnRNPDL binded to CDKN2C isoform 2 and suppressed its expression by alternative splicing. Finally, in vivo studies confirmed that the addition of siTRIM4 significantly improved the effectiveness of TQB3616. Overall, our findings suggest that TRIM4 modulates ubiquitin-mediated degradation of hnRNPDL and weakens sensitivity to CDK4/6 inhibitors in ovarian cancer treatment. TRIM4 may serve as a valuable biomarker for predicting sensitivity to CDK4/6 inhibitors in ovarian cancer.
Humans ; Female ; Ovarian Neoplasms/pathology* ; Animals ; Tripartite Motif Proteins/genetics* ; Mice ; Cyclin-Dependent Kinase 4/antagonists & inhibitors* ; Cell Line, Tumor ; Cyclin-Dependent Kinase 6/antagonists & inhibitors* ; Protein Kinase Inhibitors/pharmacology* ; Ubiquitin/metabolism* ; Xenograft Model Antitumor Assays ; Ubiquitination ; Antineoplastic Agents/pharmacology*