BACKGROUND: Biomarkers-based prediction of long-term risk of acute coronary syndrome (ACS) is scarce. We aim to develop a risk score integrating clinical routine information (C) and plasma biomarkers (B) for predicting long-term risk of ACS patients. METHODS: We included 2729 ACS patients from the OCEA (Observation of cardiovascular events in ACS patients). The earlier admitted 1910 patients were enrolled as development cohort; and the subsequently admitted 819 subjects were treated as validation cohort. We investigated 10-year risk of cardiovascular (CV) death, myocardial infarction (MI) and all cause death in these patients. Potential variables contributing to risk of clinical events were assessed using Cox regression models and a score was derived using main part of these variables. RESULTS: During 16,110 person-years of follow-up, there were 238 CV death/MI in the development cohort. The 7 most important predictors including in the final model were NT-proBNP, D-dimer, GDF-15, peripheral artery disease (PAD), Fibrinogen, ST-segment elevated MI (STEMI), left ventricular ejection fraction (LVEF), termed as CB-ACS score. C-index of the score for predication of cardiovascular events was 0.79 (95% CI: 0.76-0.82) in development cohort and 0.77 (95% CI: 0.76-0.78) in the validation cohort (5832 person-years of follow-up), which outperformed GRACE 2.0 and ABC-ACS risk score. The CB-ACS score was also well calibrated in development and validation cohort (Greenwood-Nam-D'Agostino: P = 0.70 and P = 0.07, respectively). CONCLUSIONS CB-ACS risk score provides a useful tool for long-term prediction of CV events in patients with ACS. This model outperforms GRACE 2.0 and ABC-ACS ischemic risk score.

OBJECTIVE: Several epidemiological observational studies have related particulate matter (PM) exposure to Inflammatory bowel disease (IBD), but many confounding factors make it difficult to draw causal links from observational studies. The objective of this study was to explore the causal association between PM _2.5 exposure, its absorbance, and IBD. METHODS: We assessed the association of PM _2.5 and PM _2.5 absorbance with the two primary forms of IBD (Crohn's disease [CD] and ulcerative colitis [UC]) using Mendelian randomization (MR) to explore the causal relationship. We conducted two-sample MR analyses with aggregated data from the UK Biobank genome-wide association study. Single-nucleotide polymorphisms linked with PM _2.5 concentrations or their absorbance were used as instrumental variables (IVs). We used inverse variance weighting (IVW) as the primary analytical approach and four other standard methods as supplementary analyses for quality control. RESULTS: The results of MR demonstrated that PM _2.5 had an adverse influence on UC risk (odds ratio [ OR] = 1.010; 95% confidence interval [ CI] = 1.001-1.019, P = 0.020). Meanwhile, the results of IVW showed that PM _2.5 absorbance was also causally associated with UC ( OR = 1.012; 95% CI = 1.004-1.019, P = 0.002). We observed no causal relationship between PM _2.5, PM _2.5 absorbance, and CD. The results of sensitivity analysis indicated the absence of heterogeneity or pleiotropy, ensuring the reliability of MR results. CONCLUSION Based on two-sample MR analyses, there are potential positive causal relationships between PM _2.5, PM _2.5 absorbance, and UC.
Humans ; Mendelian Randomization Analysis ; Particulate Matter/analysis* ; Polymorphism, Single Nucleotide ; Inflammatory Bowel Diseases/genetics* ; Air Pollutants/analysis* ; Crohn Disease/genetics* ; Colitis, Ulcerative/genetics* ; Genome-Wide Association Study ; Risk Factors ; Environmental Exposure

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To evaluate the clinical utility of left atrial strain parameters and left atrioventricular global longitudinal strain（LAVGLS）in detecting cardiovascular immune-related adverse events（CV-irAEs）among non-small cell lung cancer patients receiving immune checkpoint inhibitors（ICIs）.Methods:A total of 68 patients with non-small cell lung cancer were prospectively enrolled in Tianjin Medical University Cancer Institute and Hospital from October 2023 to October 2024. All patients were treated with ICIs for 6 cycles. Electrocardiogram，cardiac serological markers and echocardiography were examined before medication（T0 stage），4 cycles after medication（T1 stage）and 6 cycles after medication（T2 stage），respectively. According to the guidelines of the American Society of Clinical Oncology，all patients were divided into the CV-irAEs group（ n=14）and the No-CV-irAEs group（ n=54）. AFI software and 4D Auto LAQ software were used to calculate LVGLS，left atrial reservoir longitudinal strain（LASr），LAVGLS and a series of left atrial parameters. Cox proportional hazards regression model was applied to find the risk factors for the occurrence of CV-irAEs. ROC curve was applied to analyze the diagnostic efficiency of these parameters for CV-irAEs. Results:Fourteen patients（20.6%）developed CV-irAEs after T2 stage. After ICIs treatment，LVGLS，LASr and LAVGLS decreased in both groups，LVGLS，LASr and LAVGLS decreased more significantly in the CV-irAEs group than those in the No-CV-irAEs group（ P=0.038，0.047，0.005）. Left ventricular ejection fraction（LVEF）decreased in the CV-irAEs group at the same time（ P=0.003）. Cox multivariate analysis showed that ΔLAVGLS（the difference between stage T0 and stage T2）was a risk factor for CV-irAEs（ HR：1.395， P=0.019）. ROC curve analysis showed the area under the curve of LVGLS，LASr，LAVGLS，ΔLVGLS，ΔLASr，ΔLAVGLS，and LVEF at the T2 stage for diagnosis of CV-irAEs were 0.68，0.67，0.75，0.79，0.73，0.82，and 0.72，respectively. Conclusions:Decline of LAVGLS is a risk factor for CV-irAEs in patients with non-small cell lung cancer receiving ICIs and can be used for early detection of CV-irAEs. LASr has potential diagnostic value for CV-irAEs，but it is less valuable than LVGLS and LAVGLS.

AIM To study the chemical constituents from the leaves of Drynaria fortunei(Kunze)J.Sm.and their antioxidant activity.METHODS ODS-AG-HG,Sephadex LH-20 and semi-preparative HPLC were used for separation and purification,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The antioxidant activity was determined by DPPH mothod.RESULTS Fifteen compounds were isolated and identified as kaempferol-3-O-neohesperidoside(1),dihydrodehydrodiconiferyl alcohol(2),kaempferol-3,7-di-O-α-L-rahmnoside(3),astragalin(4),loliolid(5),trichothecene analogue(6),2,2-[bis-4-(2,3-dihydroxypropoxy)phenyl]propane(7),maculatin(8),trichothecin(9),4-[(Z)-but-2-enoyloxy]-8-chloro-12-hydroxy-7,13-epoxytrichothec-9-ene(10),8-deoxy-trichotecin(11),β-sitosterol(12),daucosterol(13),afzelin(14),samwinol(15).The IC50 values of the leaf and rhizome extracts against DPPH free radicals were(0.072±0.005),(0.287±0.012)mg/mL,respectively.CONCLUSION Compounds 1,2,5-11,15 are isolated from this plant for the first time.The leaves of D.fortunei exhibit strong antioxidant activity.

Tumors are the second leading cause of death worldwide. Exosomes are a type of extracellular vesicle secreted from multivesicular bodies, with particle sizes ranging from 40 to 160 nm. They regulate the tumor microenvironment, proliferation, and progression by transporting proteins, nucleic acids, and other biomolecules. Compared with other drug delivery systems, exosomes derived from different cells possess unique cellular tropism, enabling them to selectively target specific tissues and organs. This homing ability allows them to cross biological barriers that are otherwise difficult for conventional drug delivery systems to penetrate. Due to their biocompatibility and unique biological properties, exosomes can serve as drug delivery systems capable of loading various anti-tumor drugs. They can traverse biological barriers, evade immune responses, and specifically target tumor tissues, making them ideal carriers for anti-tumor therapeutics. This article systematically summarizes the methods for exosome isolation, including ultracentrifugation, ultrafiltration, size-exclusion chromatography (SEC), immunoaffinity capture, and microfluidics. However, these methods have certain limitations. A combination of multiple isolation techniques can improve isolation efficiency. For instance, combining ultrafiltration with SEC can achieve both high purity and high yield while reducing processing time. Exosome drug loading methods can be classified into post-loading and pre-loading approaches. Pre-loading is further categorized into active and passive loading. Active loading methods, including electroporation, sonication, extrusion, and freeze-thaw cycles, involve physical or chemical disruption of the exosome membrane to facilitate drug encapsulation. Passive loading relies on drug concentration gradients or hydrophobic interactions between drugs and exosomes for encapsulation. Pre-loading strategies also include genetic engineering and co-incubation methods. Additionally, we review approaches to enhance the targeting, retention, and permeability of exosomes. Genetic engineering and chemical modifications can improve their tumor-targeting capabilities. Magnetic fields can also be employed to promote the accumulation of exosomes at tumor sites. Retention time can be prolonged by inhibiting monocyte-mediated clearance or by combining exosomes with hydrogels. Engineered exosomes can also reshape the tumor microenvironment to enhance permeability. This review further discusses the current applications of exosomes in delivering various anti-tumor drugs. Specifically, exosomes can encapsulate chemotherapeutic agents such as paclitaxel to reduce side effects and increase drug concentration within tumor tissues. For instance, exosomes loaded with doxorubicin can mitigate cardiotoxicity and minimize adverse effects on healthy tissues. Furthermore, exosomes can encapsulate proteins to enhance protein stability and bioavailability or carry immunogenic cell death inducers for tumor vaccines. In addition to these applications, exosomes can deliver nucleic acids such as siRNA and miRNA to regulate gene expression, inhibit tumor proliferation, and suppress invasion. Beyond their therapeutic applications, exosomes also serve as tumor biomarkers for early cancer diagnosis. The detection of exosomal miRNA can improve the sensitivity and specificity of diagnosing prostate and pancreatic cancers. Despite their promising potential as drug delivery systems, challenges remain in the standardization and large-scale production of exosomes. This article explores the future development of engineered exosomes for targeted tumor therapy. Plant-derived exosomes hold potential due to their superior biocompatibility, lower toxicity, and abundant availability. Furthermore, the integration of exosomes with artificial intelligence may offer novel applications in diagnostics, therapeutics, and personalized medicine.

Objective:To evaluate the efficacy of preoperative prediction of regional lymph node (RLN) metastasis in renal cell carcinoma (RCC) using a machine learning model based on habitat imaging radiomics from renal MRI.Methods:This cross-sectional study retrospectively analyzed 220 patients with RCC who underwent nephrectomy and RLN dissection at four medical centers of Chinese PLA General Hospital from January 2010 to August 2023. The cohort included 65 patients with RLN metastasis and 155 without. A stratified random sampling method was used to divide 175 patients from the first medical center into a training set ( n=140) and an internal test set ( n=35) in an 8∶2 ratio, while 45 patients from the third, fourth, and fifth medical centers constituted the external test set. The primary RCC lesions were categorized into 15 habitat subregions based on corticomedullary-phase enhancement and T 2WI signal intensity on MRI, and the volume fractions of different subregions were analyzed. In the training cohort, radiomics features derived from the habitat subregions were used to construct a radiomics model employing various machine learning algorithms, including extremely random trees (ET), gradient boosting decision trees (GBDT), random forest (RF), and support vector machine (SVM). The optimal model was selected and combined with RLN short-axis diameter to develop a combined model. The efficacy of each model in predicting RLN metastasis was evaluated using the receiver operating characteristic (ROC) curve. Results:The volume fraction of hyper-enhanced hyper-intense regions in the non-metastatic group was significantly higher than that in the metastatic group (0.05±0.09 vs. 0.02±0.03; t=3.00, P=0.003). Among the machine learning models constructed using 15 optimal habitat radiomics features, the SVM model demonstrated the best performance, with area under the ROC curve (AUC) values of 0.85 (95% CI 0.72-0.98) in the internal test set and 0.82 (95% CI 0.67-0.98) in the external test set, surpassing those of the ET, GBDT, and RF models. The combined model, integrating the SVM model with RLN short-axis diameter, achieved AUC values of 0.94 (95% CI 0.85-1.00) in the internal test set and 0.89 (95% CI 0.78-1.00) in the external test set, with RLN short-axis diameter contributing AUC values of 0.81 (95% CI 0.66-0.96) and 0.81 (95% CI 0.68-0.94), respectively. The diagnostic sensitivity of the combined model was 91.7% in the internal test set and 85.7% in the external test set, with specificities of 78.3% and 67.7%, respectively. Conclusion:The combined model based on MRI habitat imaging radiomics and RLN short-axis diameter demonstrates excellent preoperative assessment capability for RLN metastasis in RCC.

Objective To evaluate the prognosis of infants with common Hirschsprung's disease who undergo laparoscopic-assisted Soave procedure below 6 months of age,and to explore its feasibility.Methods A retrospective analysis was conducted on the clinical data of 82 cases of common Hirschsprung's disease admitted to our department from January 2018 to August 2022.The patients were divided into two groups based on their age at the time of surgery:Young surgical age group(＜6 months,50 cases)and Old surgical age group(≥ 6 months,32 cases).All patients underwent the treatment of laparoscopic-assisted Soave procedure.The surgical time,length of hospital stay,postoperative complications,and anal function were compared between the two groups.Results There were no significant differences between young surgical age group and old surgical age group in terms of surgical time[(145.04±11.21)min vs.(149.25±12.18)min,P=0.20],length of hospital stay[(13.56+0.93)d vs.(13.91±0.99)d,P=0.55],postoperative complications[22.00％(11/50)vs.28.13％(9/32),P=0.53],and Rintala score for anal function[(18.58±1.44)vs.(17.22±1.64),P=0.06].The main postoperative complications,including enterocolitis[10.00％(5/50)vs.12.50％(4/32),P=0.72],fecal/anal incontinence[6.00％(3/50)vs.6.25％(2/32),P=0.96],and constipation[4.00％(2/50)and 6.25％(2/32),P=0.65],showed no significant differences between the two groups(all P＞0.05).However,there was a statistically significant difference in terms of bleeding volume[(7.86±2.02)ml vs.(9.13±2.17)ml,P＜0.05].No deaths occurred in this study.Conclusion Laparoscopic-assisted Soave procedure is safe and effective for infants below 6 months of age with common congenital Hirschsprung's disease.It can achieve satisfactory anal function and reduce the incidence of adverse events during the waiting period for surgery.

Objective:To investigate the prognostic effect of femoral resection on patients with soft tissue sarcoma of the thigh with cortical bone involvement.Methods:This retrospective study included patients with soft tissue sarcoma of the thigh diagnosed and treated in the Second Affiliated Hospital of Zhejiang University School of Medicine from January 2014 to December 2021. Patients were divided into two groups based on whether femoral resection and reconstruction were performed with 20 in the resection group and 86 in the non-resection group. Propensity score matching (PSM) was used to control confounding variables. Overall Survival, recurrence free survival, metastasis free survival, and postoperative functional outcomes were compared between groups before and after PSM. Cox proportional hazards regression was used to identify risk factors for death, recurrence, and metastasis.Results:Before PSM, the 5-year overall survival (OS) and recurrence-free survival (RFS) rates were 46.7% and 36.7% in the resection group, compared to 69.7% and 60.3% in the non-resection group without significant differences ( P>0.05). However, the 5-year metastasis-free survival (MFS) rate was significantly lower in the resection group (40.0%) compared to the non-resection group (73.1%) ( P=0.021). After PSM, the 5-year OS, RFS, and MFS in the resection group were 46.7%, 36.7%, and 35.9%, respectively, compared to 45.0%, 39.4%, and 67.7% in the non-resection group, with no significant differences ( P>0.05). The median postoperative MSTS functional score after PSM was significantly lower in the resection group 23(18, 25) points than in the non-resection group 26.5(24.3, 27.8) points ( U=43.000, P=0.007). Multivariate Cox regression analysis identified grade III histology ( HR=3.794, P=0.002) and tumor involvement angle around the femur greater than 180° ( HR=2.729, P=0.030) as independent risk factors for death. Age over 55 years ( HR=4.185, P=0.015), tumor diameter greater than 8 cm ( HR=4.290, P=0.014), and involvement of the intermuscular compartment ( HR=3.794, P=0.017) were associated with increased risk of local recurrence. Grade III histology ( HR=3.848, P=0.006) and involvement of the intermuscular compartment ( HR=2.500, P=0.045) were associated with distant metastasis. Conclusion:For patients with thigh soft tissue sarcoma involving femoral cortex involvement but no medullary cavity invasion, bone resection did not improve survival, recurrence or metastasis compared with patients in non-resection group. A relatively more conservative surgical approach may be advisable to preserve limb function without compromising oncological prognosis.

Objective To investigate the impact of the precision health management model on liver fibrosis,adipocytokines,and metabolic indicators in patients with non-alcoholic fatty liver dis-ease(NAFLD).Methods A total of 600 NAFLD patients were selected as study subjects and divid-ed into conventional group and precision group according to different intervention methods,with 300 patients in each group.The conventional group received routine health management,while the preci-sion group received intervention through the precision health management model.Comparisons were made between the two groups in terms of obesity indicators[waist-to-hip ratio(WHR),body mass in-dex(BMI),body fat rate(BFR),degree of obesity],fatty liver grading,liver stiffness measure-ment(LSM),and liver fibrosis indicators[laminin(LN),type Ⅳ collagen(C Ⅳ),hyaluronic acid(HA),type Ⅲ procollagen(PC Ⅲ)],hepatic adipocytokines[nuclear factor-κB(NF-κB),adi-ponectin(APN),irisin,tumor necrosis factor-α(TNF-α)],and lipid metabolism indicators[tri-glycerides(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC)]levels.Results After the intervention,the levels of WHR,BFR,BMI,degree of obesity,LSM,as well as LN,C Ⅳ,HA,PC Ⅲ,NF-κB,TNF-α,TG,LDL-C,and TC in both groups were lower than those before the intervention,and the precision group showed lower levels than the conventional group,with statistically significant differences(P＜0.05).After the intervention,the fatty liver grading in both groups was better than before intervention,and the precision group showed better fatty liver grading than the conventional group,with statistically signif-icant differences(P＜0.05).After the intervention,the levels of APN,irisin,and HDL-C in both groups were higher than those before the intervention,and the precision group showed higher levels than the conventional group,with statistically significant differences(P＜0.05).Conclusion The precision health management model can effectively improve the degree of obesity,fatty liver grading,and liver fibrosis status in NAFLD patients,reduce LSM,and regulate the levels of adipocytokines and lipid metabolism indicators,yielding significant effects.