Aim Mouse model of myocardial hypertro-phy was established via intraperitoneal injection of iso-proterenol(ISO)in mice.This approach allows for an in-depth investigation into the pharmacological effects and mechanisms of action of emodin,offering novel in-sights and directions for the improvement of myocardial hypertrophy.Methods The mice were randomly di-vided into the following groups:control group(CON),emodin group(EMO),MAPK activator control group(EMO+Ani),model group(ISO),treatment group(ISO+EMO),and activator intervention group(ISO+EMO+Ani).After treatment with emodin and inter-vention with MAPK activator,the heart weight ratio and cardiac size of each group were observed.Hematoxy-lin-eosin(HE)staining was used to observe the patho-logical changes in cardiac tissue,and kits were utilized to measure the levels of GSH,LDH,and MDA in the serum.Western blot was employed to detect the protein expression levels of inflammatory and oxidative factors,as well as p-p38,p-ERK,p38,and ERK in cardiac tis-sue.Results Emodin can significantly inhibit the production of myocardial inflammatory and oxidative factors induced by ISO,thereby effectively alleviating the degree of myocardial hypertrophy and fibrosis.Af-ter the p38/ERK signaling pathway was specifically ac-tivated by farnesol,the improvement effect of emodin on myocardial hypertrophy was weakened.Further comparison revealed that,compared with the myocardi-al hypertrophy pathological model group,the pathologi-cal protein expression levels in the farnesol-treated group showed no significant difference,and were even higher in some indicators.Conclusion Emodin can effectively inhibit the release of inflammatory factors and improve the state of oxidative stress by modulating the p38/ERK signaling pathway,thereby exerting an ameliorative effect on myocardial hypertrophy.

Objective:To investigate the completion rate of tumor evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients in the national multicenter real-world database.Methods:The prospective real-world study was conducted. The clinicopathological data of 1 074 patients who underwent surgical treatment for mid and low rectal cancer in 47 national medical institutions, including Peking Union Medical College Hospital et al, from May 12,2023 to May 11,2024 were collected. Observation indicators: (1) clinical characteristics of patients with mid and low rectal cancer; (2) initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer; (3) initial imaging evaluation of patients with mid and low rectal cancer; (4) imaging evaluation after neoadjuvant therapy for patients with mid and low rectal cancer. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M( Q1, Q3). Count data were described as absoluter numbers and/or percentages. Results:(1) Clinical characteristics of patients with mid and low rectal cancer. Of the 1 074 patients, there were 713 males and 361 females, aged 63(56,70)years. The body mass index of 1 074 patients was 24(21,26)kg/m 2.For American Society of Anesthesiologists classification, there were 147 cases of stage Ⅰ, 641 cases of stage Ⅱ, 157 cases of stage Ⅲ, 2 cases of stage Ⅳ, and there were 127 cases missing data. (2) Initial colonoscopy and pathologic evaluation of tumors in patients with mid and low rectal cancer. Of the 1 074 patients, there were 787 cases (73.28%) undergoing complete colonoscopy, and there were only 197 cases (18.34%) undergoing immunohistochemical evaluation of all four mismatch repair proteins. (3) Initial imaging evaluation of patients with mid and low rectal cancer. Of the 1 074 patients, there were 842(78.40%) patients completing magnetic resonance imaging (MRI) or ultrasound evaluation, and there were 914(85.10%) patients completing chest, abdomen, and pelvis enhanced computed tomography (CT) evaluation. In the 149 patients completing rectal ultrasound evaluation, there were 122 cases (81.88%) comple-ting T staging evaluation, and there were 81 cases (54.36%) completing N staging evaluation. In the 808 patients completing rectal MRI evaluation, there were 708 cases (87.62%) completing T staging evaluation, and there were 590 cases (73.02%) completing N staging evaluation. (4) Imaging evalua-tion after neoadjuvant therapy for patients with mid and low rectal cancer. Of the 388 patients with neoadjuvant therapy, there were 332 patients (85.57%) completing MRI or ultrasound evaluation, and there were 327 patients (84.28%) completing chest, abdomen, and pelvis enhanced CT evalua-tion. In the 70 patients completing rectal ultrasound evaluation, there were 65 cases (92.86%) com-pleting T staging evaluation, and there were 49 cases (70.00%) completing N staging evaluation. In the 327 patients completing rectal MRI evaluation, there were 246 cases (75.23%) completing T staging, and there were 228 cases (69.72%) completing N staging evaluation. Conclusion:The com-pletion rate of tumor imaging evaluation at initial assessment and after neoadjuvant therapy for mid and low rectal cancer patients on a national scale is relatively good.

Objectives:To investigate the predictive value of epicardial fat volume(EFV)and atrioventricular groove fat thickness(AVGT)—morphological biomarkers of epicardial adipose tissue—for major adverse cardiovascular events(MACE)in patients with dilated cardiomyopathy(DCM).Methods:This study enrolled 216 DCM patients.EFV and AVGT were obtained from cardiac magnetic resonance imaging(CMR).Patients were divided into event-free group(n=142)and event group(n=74)based on MACE occurrence during follow-up.Receiver operating characteristic(ROC)curve analysis was used to determine optimal cutoff values.Survival differences were assessed using Kaplan-Meier analysis,Cox proportional hazards regression analysis was used to identify independent risk factors,and restricted cubic spline(RCS)models were used to evaluate dose-response relationships.Results:AVGT and EFV were significantly higher in the event group than in event-free group(both P<0.05).ROC analysis identified optimal MACE-predicting cutoffs as follows:AVGT≥7.74 mm(area under the curve[AUC]=0.57)and EFV≥78.6 ml(AUC=0.62).Kaplan-Meier analysis revealed significantly lower MACE-free survival rates in patients with AVGT≥7.74 mm and EFV≥78.6 ml(both P<0.05).Cox regression analysis confirmed that AVGT(HR=2.18,95%CI:1.34-3.54)and EFV(HR=1.81,95%CI:1.11-2.96)were independent MACE risk factors(both P<0.05)in this patient cohort.RCS models demonstrated the significant linear associations between EFV/AVGT and MACE risk(bothoverall P<0.05).Conclusions:EFV and AVGT,the non-invasive imaging biomarkers quantifying and characterizing fat distribution,are independently correlated with elevated MACE risk in DCM patients.These metrics serve as potential prognostic indicators,enriching risk stratification indicators for early identification of high-risk patients and guiding personalized medication strategies.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Aim Mouse model of myocardial hypertro-phy was established via intraperitoneal injection of iso-proterenol(ISO)in mice.This approach allows for an in-depth investigation into the pharmacological effects and mechanisms of action of emodin,offering novel in-sights and directions for the improvement of myocardial hypertrophy.Methods The mice were randomly di-vided into the following groups:control group(CON),emodin group(EMO),MAPK activator control group(EMO+Ani),model group(ISO),treatment group(ISO+EMO),and activator intervention group(ISO+EMO+Ani).After treatment with emodin and inter-vention with MAPK activator,the heart weight ratio and cardiac size of each group were observed.Hematoxy-lin-eosin(HE)staining was used to observe the patho-logical changes in cardiac tissue,and kits were utilized to measure the levels of GSH,LDH,and MDA in the serum.Western blot was employed to detect the protein expression levels of inflammatory and oxidative factors,as well as p-p38,p-ERK,p38,and ERK in cardiac tis-sue.Results Emodin can significantly inhibit the production of myocardial inflammatory and oxidative factors induced by ISO,thereby effectively alleviating the degree of myocardial hypertrophy and fibrosis.Af-ter the p38/ERK signaling pathway was specifically ac-tivated by farnesol,the improvement effect of emodin on myocardial hypertrophy was weakened.Further comparison revealed that,compared with the myocardi-al hypertrophy pathological model group,the pathologi-cal protein expression levels in the farnesol-treated group showed no significant difference,and were even higher in some indicators.Conclusion Emodin can effectively inhibit the release of inflammatory factors and improve the state of oxidative stress by modulating the p38/ERK signaling pathway,thereby exerting an ameliorative effect on myocardial hypertrophy.

Objectives:To investigate the predictive value of epicardial fat volume(EFV)and atrioventricular groove fat thickness(AVGT)—morphological biomarkers of epicardial adipose tissue—for major adverse cardiovascular events(MACE)in patients with dilated cardiomyopathy(DCM).Methods:This study enrolled 216 DCM patients.EFV and AVGT were obtained from cardiac magnetic resonance imaging(CMR).Patients were divided into event-free group(n=142)and event group(n=74)based on MACE occurrence during follow-up.Receiver operating characteristic(ROC)curve analysis was used to determine optimal cutoff values.Survival differences were assessed using Kaplan-Meier analysis,Cox proportional hazards regression analysis was used to identify independent risk factors,and restricted cubic spline(RCS)models were used to evaluate dose-response relationships.Results:AVGT and EFV were significantly higher in the event group than in event-free group(both P<0.05).ROC analysis identified optimal MACE-predicting cutoffs as follows:AVGT≥7.74 mm(area under the curve[AUC]=0.57)and EFV≥78.6 ml(AUC=0.62).Kaplan-Meier analysis revealed significantly lower MACE-free survival rates in patients with AVGT≥7.74 mm and EFV≥78.6 ml(both P<0.05).Cox regression analysis confirmed that AVGT(HR=2.18,95%CI:1.34-3.54)and EFV(HR=1.81,95%CI:1.11-2.96)were independent MACE risk factors(both P<0.05)in this patient cohort.RCS models demonstrated the significant linear associations between EFV/AVGT and MACE risk(bothoverall P<0.05).Conclusions:EFV and AVGT,the non-invasive imaging biomarkers quantifying and characterizing fat distribution,are independently correlated with elevated MACE risk in DCM patients.These metrics serve as potential prognostic indicators,enriching risk stratification indicators for early identification of high-risk patients and guiding personalized medication strategies.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.

Mycoplasma pneumoniae pneumonia(MPP)was a respiratory disease caused by mycoplasma pneumoniae(MP),with a complex and diverse pathogenesis involving multiple modes of cell death.Recent studies showed that programmed cell death(PCD)was associated with MPP.PCD includes cell apoptosis,necrotic apoptosis,autophagy,pyroptosis,extracellular capture network,iron death,and copper death.Therefore,it was of great significance to have a deep understanding of various PCD mechanisms and their relationship with MMP,and to analyze the role of PCD in the occurrence and development mechanism of MMP.This article aims to elucidate the latest developments in PCD research in MPP,to analyze the specific role of PCD in disease progression,and to explore their potential as therapeutic targets.In order to provide theoretical basis and practical direction for optimizing the diagnosis and treatment of MPP,and also to indicate the direction for the development of new target drugs.

This study was aimed at establishing a sensitive and specific sandwich ELISA detection method for Brucella.We screened monoclonal capture antibodies and detection antibodies for Brucella detection,and optimized and determined the opti-mal antibody coating time and concentration,as well as the optimal blocking solution,blocking time,and yin-yang critical val-ue.The specificity of this method was verified by examination of other bacteria prone to cross-reacting with Brucella.The sen-sitivity of the method was verified by detection of a gradient dilution of inactivated Brucella.Moreover,the sandwich ELISA detection results were compared with test tube agglutination and qPCR results.The selected capture antibody was 4A12,and the selected detection antibody was 6C12.Experimental analysis indicated that the optimal coating concentration for the 4A12 capture antibody was 5 μg/mL,and the optimal dilution ratio for the 6C12 detection antibody was 1∶2000.The optimal coating conditions were overnight at 4℃,and blocking with 5％skim milk powder for 2 hours.The established double antibody sand-wich ELISA method reacted with only Brucella but not other bacteria,thus demonstrating the method's good specificity.Inac-tivated Brucella solution was still detectable after dilution to 1 × 105 CFU/mL,thus demonstrating the method's good sensitiv-ity.The intra-and inter batch coefficients of variation were both below 10％,thus indicating the method's good repeatability.Thus,this study successfully established a dual antibody sandwich ELISA method for Brucella detection,which has good spe-cificity and sensitivity,and might provide an effective approach for the precise diagnosis and effective prevention and control of brucellosis.

Aim To study the protective effect of a combination of IDO-1 inhibitor(3-047)with Icartin(Y003)at a mass ratio of 1∶1.6 on diabetic nephrop-athy in db/db mice and its mechanism of action.Methods After 24 weeks of treatment in db/db mice,on the basis of pharmacodynamic evaluation,16S rD-NA gene sequencing combined with untargeted metabo-lomics was used to further investigate the mechanism of improvement of diabetic nephropathy from the perspec-tive of the"microbial-intestinal-nephrotic"axis by the combination of 3-047 and Y003.Results Compared with the control group,mice in the model group showed significantly higher levels of FBG,Scr,BUN,TC,TG,LDL-C,lower levels of HDL-C(P＜0.05),significantly increased urinary albumin excretion rate,thickening of the glomerular basement membrane and dilatation of the tunica albuginea,aggravation of oxida-tive stress damage,lower abundance,structural and functional disorders of the intestinal flora.The combi-nation of 3-047 and Y003 could improve the above conditions to different degrees,significantly increase the relative abundance of Alloprevotella,Alistipes and Dubosiella,and decrease the relative abundance of Ligilactobacillus,Dubosiella and Lactococcus.A total of 11 biomarkers with significant differences were screened by metabolomics and enriched to the pathways of alanine,tyrosine and tryptophan biosynthesis,and unsaturated fatty acid biosynthesis.Conclusions The combination of 3-047 and Y003 could improve the dis-orders of glucose-lipid metabolism,reduce the structur-al and functional damage of renal tissues,and alleviate oxidative stress by regulating the intestinal flora and re-lated amino acid metabolism,and thus achieve a pro-tective effect on mice with diabetic nephropathy,dem-onstrating that the intestinal flora and the related me-tabolites are potential targets for the treatment of dia-betic nephropathy.