Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality, characterized by poor prognosis due to its high proliferative and invasive potential. Tumor metabolic reprogramming, particularly involving glucose metabolism, is essential for tumor survival. This study investigates the role of the Hippo pathway effector transcriptional co-activator with PDZ-binding motif (TAZ) in regulating gluconeogenesis and promoting tumorigenesis in HCC. Methods: TAZ expression in HCC was analyzed using The Cancer Genome Atlas data and validated in clinical samples and cell lines. TAZ was overexpressed or silenced in HCC cell lines to evaluate its effects on cell proliferation, apoptosis, migration, and invasion. The expression and prognostic relevance of the gluconeogenesis-related genes phosphoenolpyruvate carboxykinase 1 (PCK1) and glucose-6-phosphatase (G6PC) were examined, along with their correlation with TAZ expression. Tumor growth was assessed in nude mice. Interactions between TAZ and the glucocorticoid receptor (GR) were investigated using co-immunoprecipitation, immunofluorescence, and chromatin immunoprecipitation assays. Results: TAZ was significantly upregulated in HCC tissues and cell lines. TAZ overexpression enhanced proliferation, reduced apoptosis, and promoted migration and invasion. In contrast, PCK1 and G6PC were downregulated in HCC and showed a negative correlation with TAZ expression. Conclusion TAZ modulates gluconeogenesis and accelerates tumor growth, whereas its knockdown attenuates tumor progression. TAZ interacts with GR, suppressing its transcriptional activity on gluconeogenic gene promoters.

Objective To construct a prediction model for the population with hypertension and diabetes to assess the risk of chronic kidney disease (CKD), and to provide a scientific basis for formulating targeted CKD prevention and control measures. Methods Based on physical examination data from community residents aged 60 years and above in Nanjing in 2022, 10 221 patients with hypertension and diabetes were selected as the study subjects. Variables associated with CKD prevalence were screened using univariate analysis, and further variable selection was performed using LASSO regression. Finally, a CKD risk prediction model was constructed based on logistic regression. The model's performance was evaluated using the ROC curve and calibration curve. Results The prevalence rate of CKD in the study population was 22.71%, with a mean age of 71.66 years. LASSO regression identified seven variables associated with CKD: age, blood urea nitrogen (BUN), hemoglobin, uric acid, triglyceride-glucose (TyG) index, urine protein-to-creatinine ratio (UPCR), and medical insurance type. The final logistic regression model incorporated six variables: age [OR=1.067 (95% CI: 1.058-1.076)], BUN [OR=1.377 (95% CI: 1.338-1.418)], hemoglobin [OR=0.992 (95% CI: 0.989-0.995)], uric acid [OR=1.004 (95% CI: 1.003-1.004)], TyG index [OR=1.445 (95% CI: 1.324-1.577)], and self-payment medical insurance [OR=1.732 (95% CI: 1.542-1.945)]. The model had an AUC of 0.759 (95% CI: 0.747-0.770) and a Brier score of 0.140 (95% CI: 0.136-0.145), indicating good predictive performance. The calibration curve showed good agreement between the predicted risk and the observed value. Conclusion The constructed LASSO-logistic regression risk prediction model in this study can effectively assess the risk of CKD in elderly individuals aged 60 years and above with hypertension and diabetes, providing a basis for early identification of high-risk individuals and the formulation of targeted CKD prevention and control measures.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Objective To screen for key genes and important pathways common for different etiologies of acute kidney injury(AKI)by pathway-associated deep neural network and multiple machine learning algorithms.Methods AKI microarray datasets GSE30718,GSE37838,GSE53769,GSE108113,GSE125779,GSE99325,and GSE174020 downloaded from the Gene Expression Omnibus(GEO)database were merged,including 60 kidney samples from AKI patients and 79 kidney samples from healthy controls.They were divided(8∶2)into training sets and test sets,and were used to train and evaluate pathway-associated deep neural network and 4 machine learning algorithms,including least absolute shrinkage and selection operator(LASSO),random forest(RF),support vector machine-recursive feature elimination(SVM-RFE),and extreme gradient boosting(XgBoost),to screen for common key genes and pathways of different etiologies of AKI.The downloaded datasets GSE99340 and GSE1563 were merged,including 43 kidney samples from AKI patients and 36 kidney samples from healthy controls,which were used as external validation sets for LASSO model and nomogram performance test based on the final screened genes.The pathway-associated deep neural network and machine learning algorithms were evaluated using receiver operating characteristic curves,precision,recall,accuracy,and F1-score.The immune cell infiltration characteristics were explored in AKI via cell-type identification by estimating relative subsets of RNA transcripts(CIBERSORT),and Pearson correlation coefficients were used to evaluate the correlation between the final screened common key genes and immune cell infiltration levels.Results The pathway-associated deep neural network trained by 5-fold cross validation produced an area under curve(AUC)of 0.914 5±0.007 0,a precision of 0.750 0±0.044 0,a recall of 0.923 1±0.048 0,an accuracy of 0.838 7±0.016 0,and an F1-score of 0.827 6±0.020 0 in the test set,yielding a robust and highly accurate classification performance for AKI,and identified key pathways and a subset of candidate genes.The 4 machine learning algorithms all achieved high discriminative performance for AKI in the test set with AUC≥0.860,precision≥0.750,recall≥0.800,and F1-score≥0.774,and screened 7 common key genes for AKI with different etiologies,including CD86,C-X-C motif chemokine ligand 10(CXCL10),dynamin 2(DNM2),proto-oncogene FOS,transcription factor 12(TCF12),VGF nerve growth factor inducible(VGF),and A kinase anchoring protein 5(AKAP5).Based on the final screened common key genes,the LASSO model had an AUC of 0.940 4 for the test set and an AUC of 0.944 4 for the external validation,and the model showed a very high discriminatory ability for the AKI,which demonstrated the overall regulatory performance of the genes.The nomogram constructed based on the screened 7 genes demonstrated the highest classification performance with an AUC of 0.928 9,validating the outstanding contribution and overall action performance of the screened individual genes.Immune cell infiltration analysis showed that there were significant differences in B cells na?ve,mast cells activated,monocytes,macrophages M1,B cells memory,and dendritic cells activated between AKI samples and healthy control samples(all P＜0.05).Macrophages M1 and monocytes were positively correlated with CD86 and CXCL10,mast cells activated were positively correlated with FOS,and B cells na?ve were negatively correlated with CD86 and CXCL10(all P＜0.01).Mast cells activated were positively correlated with VGF and negatively correlated with CD86 and TCF12,while memory B cells were positively correlated with CD86(all P＜0.05).Conclusion Strategy combining pathway-associated deep neural network and multiple machine learning classifiers can mine high-value key genes from high-dimensional,complex and heterogeneous transcriptomic data as potential targets for therapeutic interventions in AKI.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

OBJECTIVE To observe the effects of measures dominated by intensifying link quality on prevention and control of carbapenem-resistant Klebsiella pneumoniae(CRKP)among general ICU patients.METHODS The conventional intervention measures were taken from Jan.2016 to Oct.2020,which was assigned as the pre-inter-vention period;the intervention measures dominated by enhancement of link quality were taken for the general ICU patients(the study group)from Nov.2020 to Oct.2021,which was set as the intervention period,the inter-vention measures were taken for the neurosurgery ICU patients and the surgery ICU patients(the control group).A two-group interrupted time series of a quasi-experimental study was analyzed,and whether or not the intervention measures could reduce the incidence of CRKP hospital-associated infection among the general ICU patients was evaluated.RESULTS A total of 23 713 case-times of patients from three ICU wards were enrolled in the study.The incidence of CRKP hospital-associated infection among the general ICU patients was 4.49 cases per thousand patient-days during intervention period,3.71 cases per thousand patient-days during pre-intervention pe-riod,and there was no significant difference(u=-1.412,P=0.079);it was lower than 7.06 cases per thousand patient-days during nearly one year before the intervention period(from Nov.2019 to Oct.2020),and there was significant difference(u=3.128,P=0.002).The result of analysis of the interrupted time series showed that there was significant difference in the slope change between the study group and the control group after the inter-vention(P=0.035),indicating that the intervention measures could reduce the incidence of CRKP hospital-associ-ated infection in the study group,and there was significant difference in the changing trend between the study group and the control group.CONCLUSIONS The prevention and control measures for CRKP dominated by the link quality management can effectively reduce the incidence of CRKP hospital-associated infection among the gen-eral ICU patients.The prevention and control strategies may provide reference for prevention and control of CRKP in ICUs of other medical institutions.

The treatment of castration-resistant prostate cancer (CRPC) faces major challenges characterized by acquired resistance to androgen deprivation therapy (ADT) and consequent aggressive tumor progression. In this context, ubiquitination and deubiquitination modifications, as key protein post-translational modifications, play a crucial role in prostate tumourigenesis and progression. In recent years, the regulation of ubiquitination and deubiquitination in CRPC by the androgen receptor signalling pathway and the tumour microenvironment has received extensive attention, and these dynamic regulatory processes have become important molecular events driving CRPC progression by affecting the proliferation, metastasis, and immune escape ability of tumour cells. Therefore, in-depth analysis of the mechanisms of ubiquitination and deubiquitination in CRPC will help develop new therapeutic targets and provide more therapeutic options for patients.

OBJECTIVE:In recent years,the number of clinical research reports on acupuncture and manipulation for the treatment of greater occipital neuralgia has gradually increased,but the quality is uneven.There is currently no literature evaluating the quality of published reports,which is not conducive to the promotion of clinical use of these therapies.Therefore,this article assessed the reporting quality of randomized controlled trials on acupuncture and manipulation for greater occipital neuralgia.METHODS:Cochrane Library,PubMed,Web of Science,Embase,China National Knowledge Infrastructure(CNKI),VIP,WanFang Data,and Chinese BioMedical Literature Database(CBM)from inception to May 20,2024 were searched.The reporting quality of included randomized controlled trials was independently evaluated by two investigators using the CONSORT statement,STRICTA checklist,and Cochrane bias of risk assessment tool.A third investigator resolved any disagreement.RESULTS:A total of 62 articles were included.Based on the CONSORT statement,59.46％(22/37)of all entries had a reporting rate of less than 50％,mainly including"Identification as a randomized trial in the title(1/62,1.61％),""How sample size was determined(7/62,11.29％),""Implementation(1/62,1.61％),""Blinding(1/62,1.61％),"and"Reports of Funding(4/62,6.45％)."According to the STRICTA checklist,29.41％(5/17)of all entries had a reporting rate of less than 50％,mainly including"Details of other interventions(7/58,12.07％),""Setting and context of treatment(0/58,0％),"and"Description of participating acupuncturists(0/58,0％)."CONCLUSION:The reporting quality of randomized controlled trials on acupuncture and manipulation therapy for greater occipital neuralgia remains low.Future researchers need to make greater efforts to strictly adhere to the CONSORT statement and STRICTA checklist during trial design,implementation,and reporting.This will facilitate the standardization of research in this field and enhance the reliability and reproducibility of the research results.

Sports medicine is often associated with soft tissue injuries,with tendon and ligament injuries being the most common sports injuries accounting for 30％-40％of all injuries.Mesenchymal stem cell exosomes have the ability to escape phagocytosis and realize long-term circulation,and can also be used as drug carriers of biological materials.The use of exosomes derived from mesenchymal stem cells for cell-free treatment of soft tissue injury is the current research direction in sports medicine.In this paper,the origin of exosomes in soft tissue regeneration is summarized,with emphasis on the biological mechanism of exosomes in soft tissue injury and the progress of diagnosis and treatment related to biomaterial.