Diabetic kidney disease(DKD)is one of the most prevalent complications of diabetes mellitus,with progressive proteinuriaas the main clinical manifestation.Podocytes,a key structural component of the renal filtration barrier,age faster in diabetic state.Theirand morphologies gradually change,mainly in the form of multinucleation,widening of the peduncle,podocyte detachment and increased secretion of senescence-related secretory phenotypes.Various essential signaling pathways in senescent podocytes are altered in the high glucose environment,which results in mitochondrial dysfunction,increased oxidative stress and increased secretion of inflammatory factors.The removal of senescent podocyte,targeting and modulating senescence-related signaling pathways and blocking the secretionofsenescence associated secretory phenotypes may slow down the progression of DKD due to podocyte senescence.This article reviews the research progress on the mechanism of podocyte aging in DKD.

Obesity is a global health problem,and traditional weight loss therapies are often limited in their effectiveness and prone to accompanying adverse reactions In recent years,it has been found that the use of small interfering RNA(siRNA)technology to target regulation of obesity-related genes can effectively reduce body weight,opening up a new path for weight loss treatment.This review summarizes the mechanisms of action,delivery systems,and clinical progress of novel siRNA-based drugs,focusing on targeting genes such as transforming growth factor/cyclooxygenase,inhibin subunit beta E,and activin receptor-like kinase 7,which achieve precise targeting and enhanced therapeutic efficacy through their respective delivery systems.Meanwhile,this review also points out the drawbacks of existing drugs,including low delivery efficiency,risk of immune activation,and off-target effects.

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.

Objective: To analyze the characteristics of alcohol poisoning cases among minors receiving pre hospital 120 emergency services in Zhengzhou, providing evidence for regional management strategies of alcohol poisoning among minors. Methods: A retrospective study was conducted on 1 630 alcohol poisoning cases (aged 0-18 years) from Zhengzhou s 120 emergency system during 2017-2019 and 2023. Data on gender, age, occurrence timeframes were analyzed using t-test and χ 2 test for intergroup comparisons. Results: Annual cases were 291 (2017), 353 (2018), 483 (2019), and 503 (2023). Compared with 2017, male alcohol poisoning cases increased by 66.94% while female cases surged 104.35% by 2023. The peak incidence of alcohol poisoning among minors occurred among 16-18 year olds (85.40%), followed by 13-15 year olds (13.74%). Most cases clustered between 21:01-03:00 (60.43%), with male cases peaking at 22:01-23:00 (12.73%) and female cases peaking at 02:01-03:00 ( 11.25 %). Between 00:01-03:00, male cases progressively decreased while female cases increased. Severity distribution showed 355 mild cases (21.78%), 1 035 moderate cases (63.50%), and 240 severe cases (14.72%). Conclusions Zhengzhou region has experienced sustained growth in underage alcohol poisoning cases, predominantly occurring from evening to early morning with moderate severity, female cases demonstrate faster growth rates. Multifaceted regulatory measures should be implemented to strengthen supervision of underage drinking behaviors.

Ischemic heart disease(IHD)is a clinical disease characterized by reduced cardiac blood flow and im-balanced myocardial oxygen supply-demand.Previous studies have shown that stress hyperglycemia is associated with in-creased mortality in patients with acute myocardial infarction and heart failure,and is a poor prognostic risk factor for ische-mic heart disease.Stress hyperglycemia ratio(SHR)is a value calculated based on the random blood glucose and glycat-ed hemoglobin levels at admission through a mathematical model.As a novel indicator,it enables more accurate assess-ment of stress hyperglycemia.Recent studies has found that SHR is closely related to coronary artery disease,acute myo-cardial infarction,and heart failure caused by IHD.This article reviews the research progress on the association between SHR and IHD from three aspects.SHR may serve as a biochemical marker for risk stratification,prognosis assessment of IHD.

Ischemic heart disease(IHD)is a clinical disease characterized by reduced cardiac blood flow and im-balanced myocardial oxygen supply-demand.Previous studies have shown that stress hyperglycemia is associated with in-creased mortality in patients with acute myocardial infarction and heart failure,and is a poor prognostic risk factor for ische-mic heart disease.Stress hyperglycemia ratio(SHR)is a value calculated based on the random blood glucose and glycat-ed hemoglobin levels at admission through a mathematical model.As a novel indicator,it enables more accurate assess-ment of stress hyperglycemia.Recent studies has found that SHR is closely related to coronary artery disease,acute myo-cardial infarction,and heart failure caused by IHD.This article reviews the research progress on the association between SHR and IHD from three aspects.SHR may serve as a biochemical marker for risk stratification,prognosis assessment of IHD.

Obesity is a global health problem,and traditional weight loss therapies are often limited in their effectiveness and prone to accompanying adverse reactions In recent years,it has been found that the use of small interfering RNA(siRNA)technology to target regulation of obesity-related genes can effectively reduce body weight,opening up a new path for weight loss treatment.This review summarizes the mechanisms of action,delivery systems,and clinical progress of novel siRNA-based drugs,focusing on targeting genes such as transforming growth factor/cyclooxygenase,inhibin subunit beta E,and activin receptor-like kinase 7,which achieve precise targeting and enhanced therapeutic efficacy through their respective delivery systems.Meanwhile,this review also points out the drawbacks of existing drugs,including low delivery efficiency,risk of immune activation,and off-target effects.

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.

Diabetic kidney disease(DKD)is one of the most prevalent complications of diabetes mellitus,with progressive proteinuriaas the main clinical manifestation.Podocytes,a key structural component of the renal filtration barrier,age faster in diabetic state.Theirand morphologies gradually change,mainly in the form of multinucleation,widening of the peduncle,podocyte detachment and increased secretion of senescence-related secretory phenotypes.Various essential signaling pathways in senescent podocytes are altered in the high glucose environment,which results in mitochondrial dysfunction,increased oxidative stress and increased secretion of inflammatory factors.The removal of senescent podocyte,targeting and modulating senescence-related signaling pathways and blocking the secretionofsenescence associated secretory phenotypes may slow down the progression of DKD due to podocyte senescence.This article reviews the research progress on the mechanism of podocyte aging in DKD.

Objective To investigate the effect of hypoxia-induced factor 1α and 2α(HIF-1α and HIF-2α)on ethanol-in-duced intestinal epithelium cellular barrier dysfunction of colorectal adenocarcinoma cell(Caco-2)monolayers and its mechanism.Methods Intestinal epithelium monolayer cellular barrier model was obtained by Caco-2 in vitro and induced by ethanol with different concentrations.The cell viability was measured by MTT method.Caco-2 cells were treated with or without ethanol according to the opti-mum concentration and time.The secretions of interleukin 1 β(IL-1 β)and interleukin 6(IL-6)were detected by ELISA.The expres-sions of HIF-lα,HIF-2α,and Neu3 were analyzed by Western blot and RT-PCR.The permeability of Caco-2 cell monolayers was evaluated by transepithelial electrical resistance(TEER).Next,Caco-2 cells were transfected with small interfering RNA(siRNA)to knock down the expression of HIF-1α and HIF-2α.The cell viability,the levels of IL-1 β and IL-6,and the expression of Neu3 and TEER in each group were detected,respectively.Then,the expression of Neu3 was inhibited with siRNA to assess the permeability of Ca-co-2 cell monolayers by TEER.Results The inhibitory effect of ethanol on Caco-2 cells was dose-dependent when the concentration of ethanol was higher than 5％.When Caco-2 cells were treated with ethanol with a concentration of 5％for one hour,the levels of proinflammatory cytokines IL-1 β and IL-6 were promoted.Compared to the control group,ethanol also induced the expression of HIF-1α,HIF-2α,Neu3 and reduced TEER values(P＜0.05).After HIF-1α or HIF-2α siRNA interference in ethanol-induced Caco-2 cells,the cell viability was inhibited,the secretions of IL-1 β and IL-6 were significantly elevated and the values of TEER were decreased(P＜0.05).Interestingly,the expression of Neu3 was inhibited when HIF-2α was deleted but not HIF-1α(P＜0.05).Furthermore,TEER analysis showed an increased cellular permeability when the expression of Neu3 was inhibited(P＜0.05).Conclusion The HIF-1α or HIF-2α signal pathway may be involved regulation process of ethanol-induced increased permeability of the intestinal epithelium cellular barrier.In this process,Neu3 may be mediated by HIF-2α but not HIF-1α,contributing to intestinal epithelium cellular barrier dysfunction in ethanol-induced Caco-2.