With the widespread use of antibiotics, drug-resistant bacterial infections have become a significant threat to human health. Finding new antibacterial strategies that can effectively control drug-resistant bacterial infections has become an urgent task. Unlike small molecule drugs that target bacterial proteins, antisense oligonucleotide (ASO) can target genes related to bacterial resistance, pathogenesis, growth, reproduction and biofilm formation. By regulating the expression of these genes, ASO can inhibit or kill bacteria, providing a novel approach for the development of antibacterial drugs. To overcome the challenge of delivering antisense oligonucleotide into bacterial cells, various drug delivery systems have been applied in this field, including cell-penetrating peptides, lipid nanoparticles and inorganic nanoparticles, which have injected new momentum into the development of antisense oligonucleotide in the antibacterial realm. This review summarizes the current development of small nucleic acid drugs, the antibacterial mechanisms, targets, sequences and delivery vectors of antisense oligonucleotide, providing a reference for the research and development of antisense oligonucleotide in the treatment of bacterial infections.

Hepatocellular carcinoma (HCC) expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming. Aldolase A (ALDOA) plays a prominent role in glycolysis; however, little is known about its role in HCC development. In the present study, we aim to explore how ALDOA is involved in HCC proliferation. HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout, which is consistent with ALDOA overexpression encouraging HCC proliferation. Mechanistically, ALDOA knockout partially limits the glycolytic flux in HCC cells. Meanwhile, ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase; ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function. A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun, and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells. In HCC patients, the expression level of ALDOA was correlated with the phosphorylation level of c-Jun (Thr93) and poor prognosis. Remarkably, hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models, and the knockdown of A ldoa strikingly decreased HCC development in vivo. Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription, opening additional avenues for anti-cancer therapies.

Objective To compare the long-term survival of elderly patients with esophageal squamous cell carcinoma (ESCC) treated with surgical versus non-surgical treatment. Methods A retrospective analysis was conducted on the clinical data of elderly patients aged ≥70 years with ESCC who underwent esophagectomy or radiotherapy/chemotherapy at Sichuan Cancer Hospital from January 2009 to September 2017. Patients were divided into a surgical group (S group) and a non-surgical group (NS group) according to the treatment method. The propensity score matching method was used to match the two groups of patients at a ratio of 1∶1, and the survival of the two groups before and after matching was analyzed. Results A total of 726 elderly patients with ESCC were included, including 552 males and 174 females, with 651 patients aged ≥70-80 years and 75 patients aged ≥80-90 years. There were 515 patients in the S group and 211 patients in the NS group. The median follow-up time was 60.8 months, and the median overall survival of the S group was 41.9 months [95%CI (35.2, 48.5)], while that of the NS group was only 24.0 months [95%CI (19.8, 28.3)]. The 1-, 3-, and 5-year overall survival rates of the S group were 84%, 54%, and 40%, respectively, while those of the NS group were 72%, 40%, and 30%, respectively [HR=0.689, 95%CI (0.559, 0.849), P<0.001]. After matching, 138 patients were included in each group, and there was no statistical difference in the overall survival between the two groups [HR=0.871, 95%CI (0.649, 1.167), P=0.352]. Conclusion Compared with conservative treatment, there is no significant difference in the long-term survival of elderly patients aged ≥70 years who undergo esophagectomy for ESCC. Neoadjuvant therapy combined with surgery is still an important choice to potentially improve the survival of elderly patients with ESCC.

Objective To explore the value of serum matrix metalloproteinase 7 combined with glutamyl transferase and total bile acids in the diagnosis of biliary atresia.Methods 112 children hospitalized in Kunming Children's Hospital with the cholestatic jaundice from July 2023 to September 2024 were selected as the research subjects.According to the surgical exploration,intraoperative cholangiography,liver biopsy and follow-up,the children were divided into the biliary atresia group(BA)(n=52)and non-biliary atresia group(Non-BA)(n=60)respecvely.The age,gender,serum matrix metalloproteinase 7(MMP-7),glutamyl transferase(GGT),alanine aminative aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TB),direct bilirubin(DB),total bile acid(TBA)and aspartate aminotransferase/platelet index(APRI)were compared between the two groups.Statistically significant indicators were included in receiver operating characteristic curve(ROC)analysis,and the area under the ROC curve(AUC)and optimal diagnostic margin(Youden index)were calculated.Results There was no significant difference in age,ALT,AST,DB,TB and APRI levels between the two groups of patients(P>0.05);There was a difference in gender composition ratio between the two groups(P=0.006);MMP-7,GGT,TBA levels in the BA group were significantly higher than those in the Non-BA group,and the difference was statistically significant(P<0.05);the AUC of MMP-7,GGT,and TBA in diagnosing BA were 0.946(95%CI 0.897～0.996),0.857(95%CI 0.789～0.926),0.654(95%CI 0.552～0.755)respectively;When the cut-off value of MMP-7 was 22.37 ng/ml,the sensitivity and specificity for diagnosing BA were 0.923 and 0.933 respectively;When the cut-off value of GGT was 151.5 U/L,the sensitivity and specificity of diagnosing BA were 0.885 and 0.733 respectively;When the cut-off value of TBA was 119.5 μmol/L,the sensitivity and specificity of diagnosing BA were 0.788 and 0.500,respectively.The AUC of MMP-7+GGT and MMP-7+TBA combined to diagnose BA were 0.971(95%CI 0.946～0.997)and 0.943(95%CI 0.889～0.996)respectively.Conclusion Serum MMP-7 has the good diagnostic value as a single indicator for diagnosing BA;MMP-7 combined with GGT is better than a single indicator for diagnosing BA;MMP-7 combined with TBA cannot improve the diagnostic efficiency.

Hepatocellular carcinoma(HCC)expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming.Aldolase A(ALDOA)plays a prominent role in glycolysis;however,little is known about its role in HCC development.In the present study,we aim to explore how ALDOA is involved in HCC proliferation.HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout,which is consistent with ALDOA overexpression encouraging HCC prolifera-tion.Mechanistically,ALDOA knockout partially limits the glycolytic flux in HCC cells.Meanwhile,ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase;ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function.A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun,and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells.In HCC patients,the expression level of ALDOA was correlated with the phosphorylation level of c-Jun(Thr93)and poor prognosis.Remarkably,hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models,and the knockdown of Aldoa strikingly decreased HCC development in vivo.Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription,opening additional avenues for anti-cancer therapies.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.

In the context of globalization,zoonosis prevention and control requires an integrated approach across human,animal,and environmental systems,including interdisciplinary and cross sectional collaboration,which impose heightened requirements for the core competencies among relevant professionals.By a systematic analysis of literature and policy documents,this study explored progress in the application of the One Health concept to the global prevention and control of zoonoses,with a focus on dissecting practi-cal achievements and empirical insights regarding policies promoting the development of core competencies among professionals in this field.By summarizing the existing core competency frameworks and their construction methods,this article also disscussed the guiding roles of existing frameworks,such as the"competencies for one health field epidemiology framework"and the"Ecohealth and One Health network competency framework"on the cultivation of professional talent.This work aimed at providing theoretical support for establishing a One Health-oriented competency framework in China,promoting multidisciplinary collaboration,offering scientific foundations for policy-making and talent cultivation,and contributing to achieving the strategic objectives of"Healthy China 2030"and the Sustainable Development Goals.

Objective To investigate the correlation between serum uric acid(SUA)levels and incident chronic kidney disease(CKD)in middle-aged and elderly Chinese population and gender differences.Methods Based on the longitudinal survey data of China Health and Retirement Longitudinal Study from 2011 to 2015,the CKD-Epidemiology Collaboration cystatin C formula was used to estimate the glomerular filtration rate(eGFR),and 4 119 participants with normal renal function(eGFR≥60 mL·min-1·1.72 m-2)at baseline were included.Incident CKD was defined as eGFR<60 mL·min-1·1.72 m-2 at the follow-up in 2015.Logistic regression analysis was used to analysis the association of SUA levels at baseline and incident CKD among different genders.Restricted cubic spline analysis was used to analyze the dose-response relationship.Results After 4-year follow-up,127 participants developed incident CKD,including 57 males and 70 females.Multivariate Logistic regression analysis showed that elevated SUA levels were independently associated with the risk of incident CKD(OR=1.532,P<0.001).For each 1 mg/dL increase in SUA,the risk of incident CKD increased by 33.6%in males(OR=1.336,P=0.012)and 77.5%in females(OR=1.755,P<0.001).Restricted cubic spline analysis showed a linear positive correlation between SUA levels and incident CKD in both males and females.Participants were divided into four groups according to SUA quartiles(Q1-Q4).Multivariate Logistic regression analysis indicated a significant increase in the risk of incident CKD in Q3 group(3.75 mg/dL4.43 mg/dL)compared with Q1 group in females(Q3 group:OR=2.571,P=0.045;Q4 group:OR=3.666,P=0.005).Conclusion SUA is an independent risk factor for incident CKD in the middle-aged and elderly population.In females,serum uric acid levels exceeding 3.75 mg/dL are associated with an increased risk of incident CKD.