Atherosclerosis (AS), the primary pathological contributor to cardiovascular diseases (CVDs), has increasingly affected younger populations due to modern dietary habits and sedentary lifestyles. Current diagnostic modalities, including ultrasound, MRI, and CT, primarily identify advanced lesions and inadequately evaluate plaque vulnerability, thereby hindering early detection. Conventional treatments, which involve long-term medications associated with side effects such as hepatic injury and surgical interventions that carry risks of restenosis and hemorrhage, underscore the urgent need for non-invasive, cost-effective early diagnostic methods and targeted therapies. Gut microbiota metabolites are pivotal in AS pathogenesis, with trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs) serving as functionally opposing biomarkers. TMAO is produced when gut bacteria, specifically Firmicutes and Proteobacteria, metabolize dietary choline and carnitine into trimethylamine (TMA), which the liver subsequently converts to TMAO via flavin-containing monooxygenase 3 (FMO3); TMAO is then excreted in urine. Variability in TMAO levels is influenced by marine food consumption and FMO3 modulation, which can be affected by genetics, age, and diet. Mechanistically, TMAO exacerbates AS by disrupting cholesterol metabolism, inducing endothelial dysfunction through the elevation of reactive oxygen species (ROS) and pro-inflammatory cytokines such as IL-6, and reducing nitric oxide levels. Additionally, TMAO activates NF-κB and NLRP3 pathways while enhancing platelet reactivity. Clinically, elevated TMAO levels correlate with early AS and serve as predictors of mortality in patients with stable coronary artery disease (CAD) and acute coronary syndrome (ACS), as well as major adverse cardiovascular events (MACE) in stroke patients. Conversely, SCFAs—namely acetate, propionate, and butyrate—are produced by gut bacteria such as Akkermansia muciniphila and Faecalibacterium prausnitzii through the fermentation of dietary fiber. These metabolites exert anti-AS effects: acetate aids in maintaining metabolic homeostasis; propionate protects endothelial function and reduces plaque area; and butyrate fortifies intestinal barriers while suppressing inflammation. Furthermore, SCFAs cross-regulate bile acid metabolism, thereby influencing TMAO levels, and antagonize the pro-inflammatory and lipid-disrupting effects of TMAO. The use of TMAO and SCFAs as standalone biomarkers is constrained by limitations. TMAO lacks specificity, while SCFA levels fluctuate based on gut microbiota and dietary intake. Traditional AS risk assessment tools, which include clinical indicators, imaging techniques, and single biomarkers such as CRP, LDL-C, and ASCVD scores, overlook gut metabolism and demonstrate inadequate performance in younger populations. This review advocates for an “antagonistic-complementary” combined strategy: utilizing acetate and TMAO for early AS, propionate and TMAO for progressive AS, and butyrate and TMAO for advanced AS, addressing endothelial dysfunction, lipid deposition, and plaque stability/thrombosis risk, respectively. For clinical application, standardization of detection methods is crucial; liquid chromatography-mass spectrometry (LC-MS) is the gold standard, necessitating a unified sample pretreatment protocol, such as extraction with 1% formic acid in methanol. Additionally, dried blood spots (DBS) facilitate non-invasive testing, provided that dietary controls are implemented prior to detection, including a 12-hour fast and avoidance of high-choline and high-fiber foods. Existing challenges encompass the absence of standardized systems, limited large-scale validation, and ambiguous interactions with conditions such as hypertension. The authors’ team has previously established connections between gut metabolites and AS, including the reduction of TMAO as a preventive measure for AS, thereby reinforcing this proposed strategy. Future research should prioritize standardization, the development of machine learning-optimized models, validation of interventions, and the exploration of multi-omics-based “gut microbiota-metabolite-vascular” networks. In conclusion, the combined detection of TMAO and SCFAs offers a novel framework for AS risk assessment, facilitating early diagnosis and targeted interventions while enhancing the integration of gut metabolism into cardiovascular disease management.

Atherosclerosis (AS), the primary pathological contributor to cardiovascular diseases (CVDs), has increasingly affected younger populations due to modern dietary habits and sedentary lifestyles. Current diagnostic modalities, including ultrasound, MRI, and CT, primarily identify advanced lesions and inadequately evaluate plaque vulnerability, thereby hindering early detection. Conventional treatments, which involve long-term medications associated with side effects such as hepatic injury and surgical interventions that carry risks of restenosis and hemorrhage, underscore the urgent need for non-invasive, cost-effective early diagnostic methods and targeted therapies. Gut microbiota metabolites are pivotal in AS pathogenesis, with trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs) serving as functionally opposing biomarkers. TMAO is produced when gut bacteria, specifically Firmicutes and Proteobacteria, metabolize dietary choline and carnitine into trimethylamine (TMA), which the liver subsequently converts to TMAO via flavin-containing monooxygenase 3 (FMO3); TMAO is then excreted in urine. Variability in TMAO levels is influenced by marine food consumption and FMO3 modulation, which can be affected by genetics, age, and diet. Mechanistically, TMAO exacerbates AS by disrupting cholesterol metabolism, inducing endothelial dysfunction through the elevation of reactive oxygen species (ROS) and pro-inflammatory cytokines such as IL-6, and reducing nitric oxide levels. Additionally, TMAO activates NF-κB and NLRP3 pathways while enhancing platelet reactivity. Clinically, elevated TMAO levels correlate with early AS and serve as predictors of mortality in patients with stable coronary artery disease (CAD) and acute coronary syndrome (ACS), as well as major adverse cardiovascular events (MACE) in stroke patients. Conversely, SCFAs—namely acetate, propionate, and butyrate—are produced by gut bacteria such as Akkermansia muciniphila and Faecalibacterium prausnitzii through the fermentation of dietary fiber. These metabolites exert anti-AS effects: acetate aids in maintaining metabolic homeostasis; propionate protects endothelial function and reduces plaque area; and butyrate fortifies intestinal barriers while suppressing inflammation. Furthermore, SCFAs cross-regulate bile acid metabolism, thereby influencing TMAO levels, and antagonize the pro-inflammatory and lipid-disrupting effects of TMAO. The use of TMAO and SCFAs as standalone biomarkers is constrained by limitations. TMAO lacks specificity, while SCFA levels fluctuate based on gut microbiota and dietary intake. Traditional AS risk assessment tools, which include clinical indicators, imaging techniques, and single biomarkers such as CRP, LDL-C, and ASCVD scores, overlook gut metabolism and demonstrate inadequate performance in younger populations. This review advocates for an “antagonistic-complementary” combined strategy: utilizing acetate and TMAO for early AS, propionate and TMAO for progressive AS, and butyrate and TMAO for advanced AS, addressing endothelial dysfunction, lipid deposition, and plaque stability/thrombosis risk, respectively. For clinical application, standardization of detection methods is crucial; liquid chromatography-mass spectrometry (LC-MS) is the gold standard, necessitating a unified sample pretreatment protocol, such as extraction with 1% formic acid in methanol. Additionally, dried blood spots (DBS) facilitate non-invasive testing, provided that dietary controls are implemented prior to detection, including a 12-hour fast and avoidance of high-choline and high-fiber foods. Existing challenges encompass the absence of standardized systems, limited large-scale validation, and ambiguous interactions with conditions such as hypertension. The authors’ team has previously established connections between gut metabolites and AS, including the reduction of TMAO as a preventive measure for AS, thereby reinforcing this proposed strategy. Future research should prioritize standardization, the development of machine learning-optimized models, validation of interventions, and the exploration of multi-omics-based “gut microbiota-metabolite-vascular” networks. In conclusion, the combined detection of TMAO and SCFAs offers a novel framework for AS risk assessment, facilitating early diagnosis and targeted interventions while enhancing the integration of gut metabolism into cardiovascular disease management.

Background/Aims: Chronic constipation is prevalent yet under-diagnosed across Asia, compromising quality of life and burdening healthcare systems. Cultural stigma, varied diets, and limited access to standardized diagnostic tools delay timely care. Methods: The Bali Chronic Constipation Roundtable in November 2024, brought together experts from 11 Asian countries. The group reviewed epidemiological data, analyzed multinational questionnaire on clinical practice pattern, and conducted structured discussions to identify key barriers and propose region-specific recommendations. Results: Chronic constipation prevalence varies across Asia, ranging from 1.8% in India to 16.6% in Japan, with women and the elderly disproportionately affected. Under-reporting persists owing to cultural taboos and widespread self treatment with laxatives and traditional medications. Although the Rome IV criteria remains the global standard, they may not fully reflect Asian symptom profiles, and diagnosis is limited by scarce motility laboratories. First line therapies such as dietary-fiber optimization and osmotic laxatives are widely available, but newer pharmacotherapies (prucalopride, linaclotide, lubiprostone, and elobixibat) remain costly and unevenly accessible. Biofeedback for dyssynergic defecation is underutilized due to limited availability. Experts recommend expanded regional research on to refine diagnostic criteria, coupled with enhanced physician education and public awareness. They advocate accessibility to second-line and novel therapies that incorporate culturally attuned regional guidelines, and improved access to gastrointestinal motility testing. Conclusions The Bali Chronic Constipation Roundtable highlighted Asia’s need for region specific diagnostics and management. Addressing diagnostic and treatment gaps will improve outcomes, while ongoing researcher clinician policy collaboration must standardize guidelines, advance research, and ensure equitable care across Asia.

Objective: To evaluate the feasibility of dynamic contrast-enhanced MRI (DCE-MRI) in differentiating tumor deposits (TDs) from metastatic lymph nodes (MLNs) in rectal cancer. Materials and Methods: A retrospective analysis was conducted on 70 patients with rectal cancer, including 168 lesions (70 TDs and 98 MLNs confirmed by histopathology), who underwent pretreatment MRI and subsequent surgery between March 2019 and December 2022. The morphological characteristics of TDs and MLNs, along with quantitative parameters derived from DCE-MRI (K trans , kep, and v e) and DWI (ADCmin, ADCmax, and ADCmean), were analyzed and compared between the two groups.Multivariable binary logistic regression and receiver operating characteristic (ROC) curve analyses were performed to assess the diagnostic performance of significant individual quantitative parameters and combined parameters in distinguishing TDs from MLNs. Results: All morphological features, including size, shape, border, and signal intensity, as well as all DCE-MRI parameters showed significant differences between TDs and MLNs (all P < 0.05). However, ADC values did not demonstrate significant differences (all P > 0.05). Among the single quantitative parameters, v e had the highest diagnostic accuracy, with an area under the ROC curve (AUC) of 0.772 for distinguishing TDs from MLNs. A multivariable logistic regression model incorporating short axis, border, v e, and ADC mean improved diagnostic performance, achieving an AUC of 0.833 (P = 0.027). Conclusion The combination of morphological features, DCE-MRI parameters, and ADC values can effectively aid in the preoperative differentiation of TDs from MLNs in rectal cancer.

High mobility group box protein 1(HMGB1)is one of the most widely expressed protein member in the HMGs family,which is well known for its involvement in the body inflammatory response.Previous researches have found that it plays a significant role in cell migration,immune identification and neuroprotection.Spinal cord injury is a disease that causes severe damage to the nervous system,and neural circuits are disrupted after a spinal cord injury,which leads to many conditions including ischemia and hypoxia,inflammatory responses,demyelinating lesions,and glial scar formation that are detrimental to nerve regeneration and repair,making it one of the most difficult diseases to treat in the modern spinal surgery field.HMGB1 is upregulated after spinal cord injury,thereby regulating neuroinflam-matory responses,and participating in the neuronal apoptosis,promoting neuronal regeneration,and inducing neural stem cell differentiation and migration,which plays an important role in the process of neural function recovery.This paper summarizes the structure and function of HMGB1,as well as its role in spinal cord injury,in order to provide direction for founding therapeutic target for neurological function recovery after spinal cord injury.

Objective:To establish a TaqMan-MGB probe-based method for detecting the polymorphic loci C677T and A1298C of the MTHFR gene.Methods:Specific primers and TaqMan-MGB probes targeting the C677T and A1298C polymorphic loci of the MTHFR gene were designed and optimized based on the gene sequence information.A real-time quantitative PCR detection system was established.Gradient dilution experiments were conducted to determine the limit of detection,and reproducibility experiments were performed to evaluate detection consistency.Specificity was validated using wild-type and mutant plasmid templates.The method was applied to detect 56 clinical samples,and its accuracy and practicality were assessed through comparison with traditional Sanger sequencing.Results:The TaqMan-MGB probe method demonstrated high specificity for detecting the C677T and A1298C loci,with no cross-reactivity between wild-type and mutant probes,enabling accurate genotype differentiation.Sensitivity experiments revealed detection limits of 1.13 × 103 copies/μL for C677T and 8.39 × 101 copies/μL for A1298C.Reproducibility experiments showed coefficients of variation below 1％,indicating stable and reliable results.Among the 56 clinical samples,the overall detection rate for the C677T locus was 86.99％,and for the A1298C locus,it was 97.92％.The TaqMan-MGB method exhibited good concordance with Sanger sequencing results.Conclusion:The TaqMan-MGB method exhibits high specificity,sensitivity,and excellent reproducibility in detecting the polymorphic loci C677T and A1298C of the MTHFR gene,making it suitable for rapid detection in large-scale clinical samples.This method provides an effective molecular diagnostic tool for the early diagnosis and prevention of folate-related diseases.

Objective:To investigate the effects of combination therapy with aqueous extract of corn silk(CS)and training on exercise capacity and glycolipid metabolism in mice with metabolic syndrome(MS).Methods:In this study,db/db mice were used as the animal model of MS.The mice were administered aqueous extract of CS via gavage and subjected to different intensities of training for 12 weeks(3 months).The specific experimental design was as follows:24 db/db mice were randomly divided into four groups on average:negative control group(NC),aqueous extract of CS group(CS),aqueous extract of CS+moderate-intensity training group(CS+MT),and CS aqueous extract of CS+high-intensity training group(CS+HT).The maximum running speed,forelimb grip strength,body weight and fasting blood glucose of mice were measured before and after treatment.After the intervention,oral glucose tolerance test(OGTT)and insulin tolerance test(ITT)were conducted to assess glucose metabolism,while serum triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)levels were measured to evaluate lipid metabolism.Results:After 3 months of intervention,there were significant differences in the maximum running speed and forelimb grip strength among the four groups(P＜0.05).The maximum running speed and forelimb grip strength of CS group,CS+MT group and CS+HT group were higher than those of NC group(P＜0.05).The CS+MT group exhibited higher forelimb grip strength,and the CS+HT group showed higher maximum running speed and forelimb grip strength compared to the CS group(P＜0.05),while no significant difference was found between the CS+MT and CS+HT groups(P＞0.05).Significant differences in body weight were observed among the four groups after 3 months of intervention(P＜0.05).Specifically,the CS+MT and CS+HT groups exhibited significantly lower body weight compared to both the NC and CS groups(P＜0.05),with the CS+MT group having the lowest body weight(P＜0.05).Fasting blood glucose levels also differed significantly among the groups after 2 and 3 months of intervention(P＜0.05).The CS,CS+MT,and CS+HT groups had lower fasting blood glucose levels compared to the NC group(P＜0.05),with the CS+MT and CS+HT groups showing the lowest levels(P＜0.05).No significant difference was found between the CS+MT and CS+HT groups(P＞0.05).After 3 months of intervention,significant differences in the area under the curve(AUC)of OGTT and ITT were observed among the four groups(P＜0.05).The AUC of OGTT and ITT were significantly lower in the CS,CS+MT,and CS+HT groups compared to the NC group(P＜0.05).The CS+MT and CS+HT groups exhibited the lowest AUC values for both OGTT and ITT(P＜0.05),with the CS+MT group showing the lowest AUC for OGTT(P＜0.05).Significant differences in serum lipid levels were observed among the four groups after 3 months of intervention(P＜0.05).TG,TC,and LDL-C levels were significantly lower,while HDL-C levels were higher in the CS,CS+MT,and CS+HT groups compared to the NC group(P＜0.05).The CS+MT group had the lowest TG levels and the highest HDL-C levels compared to the CS+HT group(P＜0.05),with no significant differences in TC and LDL-C levels between these two groups(P＞0.05).Conclusion:Aqueous extract of CS combined with different intensity training can significantly improve the exercise capacity and glycolipid metabolism of MS mice and reduce body weight,especially CS combined with MT treatment is more effective in improving lipid metabolism.In addition,when combined with HT,aqueous extract of CS can also play an auxiliary role in reducing the side effects of high-intensity exercise and improving the therapeutic effect.

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 analyze the epidemiological characteristics of human papillomavirus(HPV)infection in women in the Zhongguancun area of Beijing,and to evaluate the infection rates and genotype distribution between different populations and age groups.Methods A retrospective analysis was conducted on HPV genotyping results of 13,105 women who visited the gynecology outpatient department or underwent routine health check-ups at Zhongguancun Hospital from March 2019 to April 2024.High-risk HPV genotypes(15 types)were detected using a fluorescence PCR assay.Positive cases were classified as single,dual or multiple(≥3)infections based on the number of genotypes.Subjects were stratified into six age groups(≤30,31-40,41-50,51-60,61-70,and≥71 years),and the characteristics of infection by type and age group were analyzed.Results The overall HPV positivity rate was 10.78%(1,413/13,105),with a significantly higher rate in the outpatient group than that in the health check-up group(16.36%vs.6.06%,P<0.01).The three most prevalent genotypes were HPV52(18.83%),HPV58(13.85%),and HPV16(11.28%).Single infections accounted for 79.19%of cases,dual infections for 15.93%and multiple infections for 4.88%.Age distribution showed a U-shaped pattern,with higher infection rate in women aged≤30 years(15.06%)and 61-70 years(13.19%),and the lowest rate in the≥71 years(8.09%).Notably,women aged≤30 years had the highest proportion of multiple infections(31.72%).Conclusion These findings provide a basis for cervical cancer screening strategies,HPV vaccination promotion and individualized prevention of cervical cancer in this region.

Chronic kidney disease(CKD)is a chronic disease characterized by renal structural damage and dysfunction.At present,there is still a lack of effective therapeutic drugs and prevention and treatment methods for CKD in clinical practice.More and more studies have shown that necroptosis,as a new type of programmed cell death,plays a vital role in the onset and progression of CKD.Targeting key molecules in the necroptosis pathway,such as RIPK1,RIPK3 and MLKL,the development of small molecule inhibitors has become an emerging strategy for the treatment of CKD,and has shown significant potential to pro-tect the kidneys and alleviate renal fibrosis in a variety of in vitro and in vivo models.Therefore,this article summarizes the re-search progress of the mechanism of necroptosis in recent years,and focuses on the potential role of necroptosis in the pathogene-sis of CKD and the therapeutic potential of targeting this path-way,providing a new perspective and research direction for the prevention and treatment of CKD in the future.