Microbial-derived metabolites are important mediators of host-microbial interactions. In recent years, the role of intestinal microbial metabolites in colorectal cancer has attracted considerable attention. These metabolites, which can be derived from bacterial metabolism of dietary substrates, modification of host molecules such as bile acids, or directly from bacteria, strongly influence the progression of colitis-associated cancer (CAC) by regulating inflammation and immune response. Here, we review how microbiome metabolites short-chain fatty acids (SCFAs), secondary bile acids, polyamines, microbial tryptophan metabolites, and polyphenols are involved in the tumorigenesis and development of CAC through inflammation and immunity. Given the heated debate on the metabolites of microbiota in maintaining gut homeostasis, serving as tumor molecular markers, and affecting the efficacy of immune checkpoint inhibitors in recent years, strategies for the prevention and treatment of CAC by targeting intestinal microbial metabolites are also discussed in this review.
Humans ; Gastrointestinal Microbiome/physiology* ; Animals ; Carcinogenesis/metabolism* ; Colitis-Associated Neoplasms/microbiology* ; Fatty Acids, Volatile/metabolism* ; Bile Acids and Salts/metabolism* ; Colitis/microbiology*

Objective To observe the therapeutic effects of Tongluo Baoshen Prescription on IgA nephropathy rats;To explore its mechanism.Methods Totally 130 SD rats were randomly divided into a normal group(20 rats)and a modeling group(110 rats).After establishing the IgA nephropathy model,the modeling group was further randomly divided into the model group,losartan potassium group and Tongluo Baoshen Prescription low-,medium-and high-dosage groups,with 20 rats in each group.Tongluo Baoshen Prescription low-,medium-and high-dosage groups were administered at dosages of 5.3,10.6 and 21.2 g/kg respectively,the losartan potassium group was given with the dosage of 5 mg/kg,the normal group and model group were given an equivalent amount of distilled water by gavage once daily.Blood,urine and kidney tissue samples were collected after 4 and 8 weeks of administration.The hemoglobin content was detected,urinary IL-1β,integrin α3β1 and serum albumin contents were detected by ELISA,and the mRNA and protein expressions of NF-κB p52,NF-κB p65,Rel B,c-Rel and Desmin in renal tissue were detected by RT-qPCR and Western blot,the apoptosis of renal tissue at 8 weeks of administration was detected by TUNEL staining,the expression of C3c in renal tissue was detected by immunofluorescence,the co-expression of Gprc5b,Caspase-1,NLRP3 and Nephrin were detected by immunofluorescence double labeling,the expression of Gprc5b and Nephrin in renal tissue were detected by immunohistochemistry.Results Compared with the normal group,the model group rats showed significantly increased contents of urinary IL-1β and integrin α3β1(P<0.01),with further increases in urinary integrin α3β1 over time(P<0.05);the mRNA and protein expressions of NF-κB p52,NF-κB p65,Rel B,c-Rel and Desmin in renal tissue significantly increased(P<0.01),and the proportion of apoptosis-positive cells in renal tissue significantly increased(P<0.01),immunofluorescence results revealed that C3c exhibited granular and clumpy high-intensity deposition in the mesangial area and capillary loops of the glomeruli(P<0.01),immunofluorescence double labeling showed that the expression of Gprc5b,Caspase-1 and NLRP3 in renal tissue increased(P<0.01),while Nephrin expression significantly decreased(P<0.01),immunohistochemistry analysis showed that the positive expression of Gprc5b in renal tissue significantly increased(P<0.01),while Nephrin significantly decreased(P<0.01).Compared with the model group,the urinary IL-1β and integrin α3β1 contents in the losartan potassium group and Tongluo Baoshen Prescription groups reduced after 4 and 8 weeks of treatment(P<0.05,P<0.01);the mRNA and protein expressions of NF-κB p52,NF-κB p65,Rel B,c-Rel and Desmin in renal tissue decreased(P<0.05,P<0.01),and the proportion of apoptosis-positive cells in renal tissue decreased(P<0.05),the C3c deposition in renal tissue was diminished(P<0.05,P<0.01),immunofluorescence double labeling showed that the expression of Gprc5b,Caspase-1 and NLRP3 in renal tissue were decreased(P<0.05,P<0.01),while Nephrin expression increased(P<0.05,P<0.01),immunohistochemistry analysis showed that the positive expression of Gprc5b in renal tissue decreased(P<0.05,P<0.01),while Nephrin expression increased(P<0.05,P<0.01).Conclusion Tongluo Baoshen Prescription has a protective effect on the kidney of IgA nephropathy rats,and it can improve podocyte injury.The mechanism may be related to the inhibition of the Gprc5b/NF-κB/NLRP3 pathway.

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.

Speech prosody is a supra segmental feature of voice,which plays an important role in daily com-munication.Cochlear implantation(CI)can help the hearing-impaired children to normalize their speech,but CI children still have varying degrees of speech prosody obstacles.This paper summarizes the perception,production characteristics and intervention strategies of CI children's speech prosody at home and abroad,in order to attract the attention of education,medical,rehabilitation and academic fields to CI children's speech prosody research,and to provide reference for future intervention of CI children's speech prosody.

A solid-phase extraction-ultra-performance liquid chromatography-tandem mass spectrometry(SPE-UPLC-MS/MS)method was established for simultaneous determination of 10 kinds of neonicotinoid pesticide residues in aquaculture water.Based on the chemical properties of neonicotinoid pesticides and the matrix characteristics of aquaculture water,suitable temporary storage methods for water samples and appropriate solid-phase extraction columns were selected,and the extraction conditions(including elution solvents and sample loading volumes)were optimized.The method employed acetonitrile and 5 mmol/L ammonium acetate solution(containing 0.1%formic acid)as the mobile phase and an Oasis HLB solid-phase extraction column combined with PSA as a dispersive sorbent for sample purification.The method exhibited good linearity in detection of neonicotinoid in concentration range of 0.2-50 ng/mL(R2>0.99797),with a detection limit of 0.5 ng/L and a quantification limit of 1 ng/L,which were significantly lower than the maximum acceptable method detection limits(9-500 ng/L)for neonicotinoid insecticides in water published by the European Commission.In pond water,rice-fish water,and seawater,the average recoveries of the 10 target analytes were 74.6%-114.1%,with relative standard deviations ranging from 0.3%to 9.6%.Using this method,actual sample tests were conducted on the Pearl River water,Zhaoqing pond water,and Qingyuan rice-fish aquaculture water.The total concentration of five neonicotinoid pesticides in the Pearl River water ranged from 154.8 to 246.6 ng/L,the total concentration of four neonicotinoid pesticides in the Zhaoqing pond water was 95.0-176.1 ng/L,and the total concentration of three neonicotinoid pesticides in the Qingyuan rice-fish aquaculture water was 2.3-11.7 ng/L.This method was simple in operation,highly sensitive,and had strong resistance to interference.It was suitable for detection of trace neonicotinoid pesticides in aquaculture water and could provide technical support for construction of a green aquaculture environment and resolution of international trade disputes.

Objective:To explore the advantages of internet-based smart healthcare for full-cycle transcatheter edge-to-edge repair (TEER) management in reducing postoperative adverse events rate, improving cardiac function, and enhancing quality of life.Methods:This retrospective study enrolled patients with mitral regurgitation who underwent transcatheter TEER at Beijing Anzhen Hospital Valve Intervention Center between June 2021 and September 2023. Patients were classified into degeneration mitral regurgitation (DMR) and functional mitral regurgitation (FMR) according to etiology, with further stratification by enrollment period into usual care group (June 2021 to October 2022) and full-cycle management group (November 2022 to September 2023). The 1-year postoperative follow-up data were collected and compared between subgroups with the same etiology. Kaplan-Meier survival curves were plotted, and log-rank tests were used to compare the differences in major endpoint event-free survival rates between the two groups. Univariate and multivariate Cox regression and logistic regression analyses were performed to evaluate the impact of the full-cycle management system on patients′ outcomes.Results:A total of 130 patients were included, aged (72.0±8.6) years, including 82 (63%) males. DMR was identified in 84 cases (40 in the usual care group and 44 in the full-cycle management group), while FMR was observed in 46 cases (27 in the usual care group and 19 in the full-cycle management group). Kaplan-Meier analysis demonstrated higher 1-year major endpoint event-free survival rates in the full-cycle management group compared to the usual care group, though the difference was not statistically significant (log-rank P>0.05). Compared to the usual care group, the full-cycle management group showed significantly higher proportions of New York Heart Association classification Ⅰ-Ⅱ patients (DMR: 67% vs. 52%, P=0.031; FMR: 68% vs. 52%, P=0.021), greater 6-minute walking distances (DMR: (346.39±70.41) m vs. (294.11±60.47) m, P=0.012; FMR: (356.60±54.68) m vs. (318.55±39.02) m, P=0.004), and superior Kansas City Cardiomyopathy Questionnaire scores (DMR: 81.50 (74.50, 85.00) points vs. 71.00 (66.00, 82.25) points, P=0.014; FMR: 83.00 (76.00, 85.00) points vs. 74.00 (70.75, 80.00) points, P=0.030). Multivariate logistic regression confirmed the full-cycle management system as an independent predictor for the above improved outcomes (all P<0.05). Conclusion:Smart healthcare-based full-cycle management improves cardiac function and quality of life in mitral regurgitation patients after TEER, demonstrating lower rates of major endpoint events compared to usual care.

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.

This study assessed the role and mechanism of the recombinant Bacillus Calmette-Gue?rin vaccine(rBCG)with c-di-AMP adjuvant in regulating metabolism and immunity in epididymal white adipose(eWAT)in mice.Male C57BL/6 mice were intravenously immunized with BCG and rBCG,and their body weights were monitored.eWAT was isolated from the mice,and the stromal vascular fractions(SVFs)cell number was counted with a hemocytometer.Sections of mouse adipose tissue were prepared,and the size,number,and morphology of eWAT adipocytes and crown-like structure(CLS)formation were compared under a microscope after HE staining.The transcription levels of lipid metabolism-associated factors,cytokines and aging-associated genes in each group were determined with qRT-PCR.The body weights of mice gradually increased after immunization with BCG and rBCG.The proportions of eWAT increased,and the SVFs cell number decreased,in rBCG immunized mice.HE staining indicated that BCG immunization promoted hyperplasia,whereas rBCG immunization promoted hypertrophy of eWAT adipocytes;moreover,both BCG and rBCG immunization induced CLS formation in eWAT.The qRT-PCR results indicated that rBCG immunization inhibited the expression of genes associated with lipolysis and energy expenditure in eWAT.BCG immunization had little effect on cytokine transcription,whereas rBCG significantly induced the transcription of IFN-γ and IL-1Ra,and inhibited that of IL-15 and IL-2,but did not induce the expression of aging-associated genes.Thus,rBCG immunization induced eWAT adipocyte hypertrophy,which was associated with the inhibition of eWAT lipolysis and the regulation of cytokine expression.