Obesity represents a critical global health challenge characterized by a complex pathogenesis involving dysregulated adipogenesis and lipid metabolism. In recent years, long non-coding RNAs (lncRNAs) have been established as crucial regulators in the initiation and progression of obesity. These RNA molecules, typically exceeding 200 nucleotides in length, have emerged as key modulators of various biological processes through multiple molecular mechanisms. This review innovatively defines lncRNAs as “molecular switches” in energy metabolism—they regulate adipogenesis and lipid metabolism through key signaling pathways, and exert bidirectional control over obesity via ceRNA mechanisms or recruitment of chromatin-modifying complexes in tissues such as adipose and liver. Additionally, circulating lncRNAs, owing to their tissue specificity and stability, hold promise as non-invasive liquid biopsy biomarkers for obesity and related metabolic disorders. Furthermore, we systematically summarize lncRNA-based intervention strategies, including targeting pathogenic lncRNAs using antisense oligonucleotides (ASOs) or CRISPR/Cas gene editing systems, utilizing viral vectors (such as adeno-associated virus, AAV) to deliver or mimic beneficial lncRNAs in target tissues, and employing exercise as a non-pharmacological intervention that ameliorates obesity and its related complications at multiple levels, offering novel insights for personalized therapeutic approaches. We also critically assess the current challenges in clinical translation, particularly addressing issues related to delivery efficiency, target specificity, and long-term safety concerns. Future research should focus on the following directions: integrating multi-omics with functional screening to elucidate the regulatory networks of lncRNAs in obesity and its complications; leveraging artificial intelligence to construct predictive models of lncRNA-target gene interactions; developing efficient and safein vivo delivery systems, and optimizing drug design to enhance specificity and safety; establishing highly sensitive detection methods and stable circulating lncRNA biomarkers to enable precise patient stratification and real-time monitoring of therapeutic responses; investigating the synergistic effects of lncRNAs with existing treatments (e.g., GLP-1 receptor agonists, lifestyle interventions) to develop combination therapies and establish a multidimensional, personalized precision medicine framework for obesity. This review aims to provide novel perspectives for understanding the molecular mechanisms underlying obesity and to establish a solid theoretical foundation for developing lncRNA-targeted precision medicine strategies against obesity and its associated metabolic complications.

Obesity represents a critical global health challenge characterized by a complex pathogenesis involving dysregulated adipogenesis and lipid metabolism. In recent years, long non-coding RNAs (lncRNAs) have been established as crucial regulators in the initiation and progression of obesity. These RNA molecules, typically exceeding 200 nucleotides in length, have emerged as key modulators of various biological processes through multiple molecular mechanisms. This review innovatively defines lncRNAs as “molecular switches” in energy metabolism—they regulate adipogenesis and lipid metabolism through key signaling pathways, and exert bidirectional control over obesity via ceRNA mechanisms or recruitment of chromatin-modifying complexes in tissues such as adipose and liver. Additionally, circulating lncRNAs, owing to their tissue specificity and stability, hold promise as non-invasive liquid biopsy biomarkers for obesity and related metabolic disorders. Furthermore, we systematically summarize lncRNA-based intervention strategies, including targeting pathogenic lncRNAs using antisense oligonucleotides (ASOs) or CRISPR/Cas gene editing systems, utilizing viral vectors (such as adeno-associated virus, AAV) to deliver or mimic beneficial lncRNAs in target tissues, and employing exercise as a non-pharmacological intervention that ameliorates obesity and its related complications at multiple levels, offering novel insights for personalized therapeutic approaches. We also critically assess the current challenges in clinical translation, particularly addressing issues related to delivery efficiency, target specificity, and long-term safety concerns. Future research should focus on the following directions: integrating multi-omics with functional screening to elucidate the regulatory networks of lncRNAs in obesity and its complications; leveraging artificial intelligence to construct predictive models of lncRNA-target gene interactions; developing efficient and safein vivo delivery systems, and optimizing drug design to enhance specificity and safety; establishing highly sensitive detection methods and stable circulating lncRNA biomarkers to enable precise patient stratification and real-time monitoring of therapeutic responses; investigating the synergistic effects of lncRNAs with existing treatments (e.g., GLP-1 receptor agonists, lifestyle interventions) to develop combination therapies and establish a multidimensional, personalized precision medicine framework for obesity. This review aims to provide novel perspectives for understanding the molecular mechanisms underlying obesity and to establish a solid theoretical foundation for developing lncRNA-targeted precision medicine strategies against obesity and its associated metabolic complications.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

Objective:To investigate immunomodulatory effects of methionine enkephalin(MENK)on macrophages,and to explore effect of opsonizing receptors in anti-influenza virus infection of macrophages.Methods:Potential targets for antiviral effects of MENK on macrophages were explored by network pharmacology.Proteomics analysis was used to identify differentially expressed pro-teins(DEPs)in macrophages of MENK-PR8 and PR8 groups.DEPs were analyzed by bioinformatics,and key factors were verified by qPCR and Western blot.Results:MENK had 85 intersection targets with macrophages and influenza viruses,of which 7 were related to phagosome pathway(mmu04145).A total of 215 DEPs were identified by mass spectrometry,which were highly enriched in phago-some(mmu04145)and interaction of viral proteins with cytokines and cytokine receptors(mmu04061)pathways.qPCR and Western blot showed that Fc gamma receptor(FcγR)and complement receptor(CR3)related to phagosome were highly expressed.Conclu-sion:MENK enhances function of phagocytosis and killing virus by upregulating opsonizing receptors via opioid receptor,suggesting that MENK can serve as an immune modulator or a novel preventive drug for influenza viruses.

Objective:To analyze the genetic characteristics of the VWF gene c.7332G＞A nonsense mutation and explore its molecular pathogenesis.Methods:Phenotypic diagnosis of the proband was performed using VWF:Ag,VWF:RCo,FⅧ:C and multimeric analysis.The probands were genotyped by NGS whole-exome sequencing,and the sequencing results were validated by sanger sequencing.The family members were genotyped by Sanger sequencing.The VWF gene c.7332G＞A nonsense mutant plasmid was constructed.After transfection,the function of VWF gene c.7332G＞A mutant plasmid was verified at cell level in vitro.The mRNA level was detected by qRT-PCR,and the expression level of protein was detected by Western blot,the function of multimerization was verified by the multimeric analysis.Results:VWF:Ag and VWF:RCo were all less than 3％in the proband,and the multimeric analysis showed multimer deficiency.The proband was diagnosed as type 3 VWD.The homozygous nonsense mutation of VWF gene c.7332G＞A was detected by gene sequencing.The VWF mRNA level of the mutant plasmid was decreased,and the VWF protein expression in the cell supernatant was decreased,the mutant protein was truncated and the function of VWF multimerization was impaired.Conclusion:A homozygous mutation in exon 43 of VWF gene,c.7332G＞A,was responsible for the probands type 3 VWD in the proband.The mutation caused a decrease in the relative level of VWF mRNA and protein,and impaired the function of VWF multimerization.

Objective To explore the factors affecting the occurrence of transient arrhythmia after percuta-neous coronary intervention(PCI)in patients with acute coronary syndromes(ACS),to establish a risk prediction model,and to test the prediction effect.Methods 480 ACS patients who underwent PCI in Western Theater Air Force Hospital of PLA from August 2022 to February 2024 were selected as study subjects and were divided into 336 cases in the construct group and 144 cases in the validation group according to the ratio of 7:3.The data of the construct group were used to construct the model,and the validation group was used to validate the model.The patients in the constructed group were divided into 84 cases in the occurrence group and 252 cases in the non-occurrence group according to whether they had experienced postoperative transient arrhythmia,and the validation group was divided into 36 cases in the occurrence group and 108 cases in the non-occurrence group.The baseline data of the study subjects in the two groups were observed,and the predictive value of continuous variables was analyzed using the ROC experiment;the influencing factors of the occurrence of transient arrhythmia after PCI in ACS patients were analyzed using multifactorial logistic regression;the Nomogram prediction model was constructed using the R language;and the model was evaluated and validated using calibration curves and decision curves.Results The results of a one-way analysis of the constructed group showed that older age,the presence of a history of diabetes mellitus,the time from onset to admission≥6 h,and higher BNP levels were the main risk factors for the occurrence of transient arrhythmia after PCI in patients with ACS(P<0.05),and the prediction model established accordingly had an AUC of 0.865 and a 95%CI of 0.804～0.927,which was effective in predicting the occurrence of transient arrhythmia after PCI in patients with ACS.The model performed well in predicting the occurrence of transient arrhythmia after PCI,with a C-index of 0.858(0.753～0.865),and provided a good stan-dardized net benefit when its risk threshold was between 0.10 to 0.96.The validation group ROC curve and calibra-tion curve results are good,with an AUC of 0.846 and a C-index of 0.840(0.737～0.851),suggesting that the model has a good external predictive efficacy.The results of the validation group decision curve analysis indicated that the model could provide better standardized net returns when the risk threshold was between 0.06 and 0.94.Conclusion The results of univariate analysis showed that older age,the presence of a history of diabetes melli-tus,onset-to-admission time≥6 h,and higher BNP levels were the main risk factors for the occurrence of transient arrhythmia after PCI in patients with ACS,and the Nomogram model constructed on the basis of these four influenc-ing factors could effectively predict the risk of transient arrhythmia after PCI in patients with ACS.

Background and purpose:China is a country with high incidence rate and mortality of liver cancer.In 2022,there were approximately 368 000 cases of liver cancer and 317 000 deaths in China.Extending the survival period of liver cancer patients is an urgent issue that we need to address.In recent years,tyrosine kinase inhibitor(TKI)alone or in combination with immune checkpoint inhibitors have achieved good results in the treatment of primary liver cancer.However,most studies did not include the combination of transcatheter arterial chemoembolization(TACE)treatment.We speculate that combining TKI drugs with immune checkpoint inhibitors and TACE therapy may provide greater benefits to liver cancer patients.Therefore,this study aimed to evaluate the short-term efficacy and safety of TACE combined with anlotinib and sintilimab in the treatment of liver cancer.Methods:This study is a single arm phase Ⅱ clinical trial approved by the ethics committee of The Third People's Hospital of Yibin(ethical approval numbers:2022009).Inclusion criteria:① Age 18-70 years;② Primary liver cancer confirmed by clinical diagnosis or histopathology;③ Eastern Cooperative Oncology Group(ECOG)performance status score of 0-1;④ China Liver Cancer Staging(CNLC)stage Ⅱb-Ⅲb;⑤ Adequate cardiopulmonary function;⑥ Child-Pugh score≤8 points;⑦ At least one measurable tumor lesion according to the modified Response Evaluation Criteria in Solid Tumors(mRECIST)version 1.1.From November 1,2021 to March 1,2024,we recruited 61 patients,of whom 39 met the criteria.Firstly,all enrolled patients received TACE treatment.Approximately one week after the initial TACE procedure,12 mg of anlotinib(adjusted according to tolerance)was administered orally on days 1-14,every 3 weeks;Simultaneously 200 mg of sintilimab was administered intravenously on day 1,every 3 weeks.After completing 2 cycles of treatment,efficacy evaluation was conducted according to the modified Response Evaluation Criteria in Solid Tumors(mRECIST)1.1.The primary observation indicators of the study were objective response rate(ORR),and the secondary observation indicators were median progression-free survival(mPFS),disease control rate(DCR)and safety.Results:The ORR of this study was 76.9%,DCR was 94.9%,and mPFS was 9.2 months(95%CI:2.317-16.083).39 cases(100%)had grade 1-2 adverse reactions,15 cases(38.5%)had grade 3 adverse reactions,5 cases(12.8%)had grade 4 adverse reactions,and 1 patient died due to upper gastrointestinal bleeding.In the stage mainly treated with TACE combined with TKI and immunotherapy,the incidence of grade 3-4 adverse reactions was higher compared with the stage mainly treated with anlotinib combined with sintilimab.The vast majority of adverse reactions can be recovered through conventional treatment methods.Conclusion:TACE combined with anlotinib and sintilimab has a definite therapeutic effect and overall safety and controllability in the treatment of CNLC stage Ⅱb-Ⅲb liver cancer.This combination therapy may provide a new treatment model for CNLC stage Ⅱb-Ⅲb liver cancer patients.However,further exploration is needed to address the pain,vomiting,decreased appetite,liver function damage,upper gastrointestinal bleeding,and other issues caused by this treatment mode.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.

Aim To investigate the role of mesence-phalic astrocyte-derived neurotrophic factor(MANF)in the inhibitory effect of rhynchophylline(Rhy)on the malignant biological behaviors of gastric cancer cells and its underlying regulatory mechanisms.Meth-ods SGC-7901 gastric cancer cells were transfected using adenovirus and liposome transfection techniques.The experimental groups included:Control group,Rhy group,Rhy+NC group(Rhy+adenovirus-transfected MANF-irrelevant fragment),Rhy+si-MANF group(Rhy+adenovirus-transfected MANF siRNA),Vec-tor group(empty vector),OVE-MANF group(recom-binant plasmid overexpressing MANF).After 24 hours of intervention,cell proliferation,apoptosis,migra-tion,and invasion were assessed using the MTT assay,Hoechst staining,and Transwell assays,respectively.The expressions of MANF,Cyclin D1,and cleaved caspase-3 proteins were measured using Western blot.NF-κB transcriptional activity was evaluated via a lucif-erase reporter assay.Results Compared to the control group,Rhy treatment significantly inhibited gastric cancer cell growth in a dose-dependent manner(P＜0.05),induced typical apoptotic morphological chan-ges,and increased the expression of MANF and cleaved caspase-3 proteins(P＜0.05),while reduc-ing Cyclin D1 protein expression and NF-κB transcrip-tional activity(P＜0.05).Additionally,Rhy treat-ment markedly decreased cell migration and invasion capabilities(P＜0.05).In comparison to the Rhy group,adenovirus-mediated transfection of MANF siR-NA suppressed apoptosis,promoted gastric cancer cell proliferation,migration,and invasion,inhibited MANF and cleaved caspase-3 expression(P＜0.05),and enhanced Cyclin D1 protein levels and NF-κB transcriptional activity(P＜0.05).Compared to the Vector group,OVE-MANF(overexpression of MANF)induced apoptosis,suppressed proliferation,invasion,and metastasis of gastric cancer cells,upregulated MANF and cleaved caspase-3 expression(P＜0.05),and inhibited Cyclin D1 protein levels and NF-κB tran-scriptional activity(P＜0.05).Conclusion Rhy in-hibits the proliferation,migration,and invasion of gas-tric cancer cells and induces apoptosis,with its mecha-nism linked to the promotion of MANF expression and suppression of NF-κB transcriptional activity.