Both type 2 diabetes mellitus (T2DM) and metabolic associated fatty liver disease (MAFLD) fall within the spectrum of metabolic diseases, and they exhibit a bi-directional causal relationship and robust reciprocal association. Their shared pathological cornerstone is insulin resistance (IR), which involves the interplay of mitochondrial dysfunction and chronic inflammation, forming a cascading pathological process of “IR-mitochondrial dysfunction-inflammation”. This largely explains the notable upward trend in T2DM-MAFLD co-occurrence observed over recent years. Exercise intervention, as a safe and effective non-pharmacological approach, can improve the pathological progression of these patients at multiple levels. Following the logical framework of “pathogenesis-efficacy comparison-molecular mechanisms-clinical translation”, this article systematically compares the efficacy and molecular mechanisms of moderate-intensity continuous training (MICT), resistance exercise, high-intensity interval training (HIIT), and combined training. MICT reduces intrahepatic triglycerides by promoting lipolysis and improving cardiorespiratory fitness; resistance exercise increases muscle mass and basal metabolic rate, offering unique advantages in preserving muscle while reducing fat and improving insulin sensitivity; HIIT is a time-efficient exercise modality that enhances patients’ cardiorespiratory fitness and insulin sensitivity by alternating brief periods of vigorous exertion with recovery periods, with a prominent short-term triglyceride-lowering effect; combined training produces synergistic effects, comprehensively improving glucolipid metabolism and showing the best long-term adherence. Mechanistically, exercise exerts its beneficial effects through three common pathways: (1) AMPK-mediated lipid oxidation and mitochondrial biogenesis; (2) IRS/PI3K/Akt-mediated insulin signaling sensitization; and (3) Nrf2/ARE anti-oxidation and TGF-β/Smads anti-fibrosis regulation. Different exercise modalities activate these pathways with distinct emphases: MICT most directly and persistently activates the AMPK pathway; resistance exercise uniquely improves IRS/PI3K/Akt signaling through muscle mass gain; HIIT induces the highest AMPK activation intensity and triggers unique lactate-mediated signaling regulation; combined training integrates the above multiple mechanistic advantages. For clinical translation, multidisciplinary team collaboration is essential to ensure safety and adherence. Individualized prescriptions should be formulated according to the FITT-VP principle and patient phenotypes—frequency of 3-5 sessions/week of aerobic exercise combined with 2-3 sessions/week of resistance exercise; intensity of moderate-intensity (40%-60% heart rate reserve (HRR))aerobic exercise and 60%-80% of one-repetition maximum (1-RM) for resistance exercise; time of at least 150 min/week of moderate-intensity aerobic exercise, 30-60 min per session; type of combined training as the preferred modality; total volume of≥500-1 000 MET-min/week; and progression adjusted every 4-6 weeks—with real-time adjustments supported by wearable devices, ultimately forming a closed-loop management system from initial assessment to long-term follow-up. Notably, current studies have limitations such as small sample sizes and short intervention periods. Future research should focus on long-term follow-up, multi-omics biomarkers, and combined exercise-drug strategies. In conclusion, the systematic integration of structured, individualized, and sustainable exercise interventions into the multidisciplinary management pathway for patients with T2DM complicated by MAFLD is an urgent need in current clinical practice.

Developing an intelligent agent for integrated traditional Chinese and western medicine diagnosis and treatment based on clinical practice guidelines is a key approach to advancing the standardization and intelligent deve-lopment of traditional Chinese medicine （TCM） and to supporting clinical decision-making. This paper argues for the necessity of building a knowledge base using guidelines as the sole data source， systematically identifies five core methodological challenges across the entire process， and proposes corresponding solutions. An ontology framework capable of distinguishing between TCM and western medicine concepts should be designed to address the difficulty of knowledge integration. A closed-loop "algorithm-based extraction-expert review" model is adopted to reduce data extraction errors. Expert consensus is incorporated to address decision gaps in specific clinical scenarios outlined in the guidelines， while a multi-stage， standardized output process for the AI system is established to eliminate model hallucinations. Furthermore， an evaluation framework reflecting clinical applicability is developed to enhance the AI system's accuracy and stability. Throughout the research process， it is essential to ensure the in-depth and continuous participation of multidisciplinary experts， strictly control the selection and quality evaluation of guidelines， and rely on the expert consensus method to address decision gaps in the knowledge base. Additionally， continuous validation and iterative optimization of intelligent agents are required to ensure the accuracy and stability of generated outputs. Limitations remain in the mechanisms for real-time knowledge synchronization in intelligent diagnostic and treatment systems， and further validation through large-scale real-world studies is warranted.

Objective: To determine the correlation between obesity related indicators and blood lipid levels among children and adolescents. Methods: A total of 5 812 participants were included. Height, weight, body composition, waist circumference, blood pressure were measured and fasting glucose and blood lipid levels were tested based on a cross sectional survey of children and adolescents 6-17 years in Beijing, 2022-2023. The body mass index (BMI), fat mass index (FMI), body roundness index (BRI) and waist to height ratio (WHtR) were calculated. Linear and Logistic regression were used to analyze the associations between the four obesity indicators (BMI, FMI, BRI, and WHtR) and blood lipids in children and adolescents. The area under the curve (AUC) of the receiver operating characteristic (ROC) was used to evaluate differences in the associations between different obesity indicators with dyslipidemia. Results: Linear regression showed that BMI, FMI, BRI, and WHtR were positively correlated with triglyceride (TG), low density lipoprotein cholesterol (LDL-C), and non high density lipoprotein cholesterol (non HDL-C) levels (boys: β 6-9 years =0.02-0.28, β 10-17 years =0.02-0.37; girls: β 6-9 years =0.02-0.28, β 10-17 years =0.03-0.25), and negatively correlated with the high density lipoprotein cholesterol (HDL-C) level in both genders across age subgroups (boys: β BMI = -0.03, β FMI = -0.04 , β BRI =-0.09, β WHtR =-0.17; girls: β BMI =-0.03, β FMI =-0.04, β BRI =-0.11, β WHtR =-0.20) (all P <0.01). The associations between total cholesterol (TC) and remnant cholesterol (RC) levels with obesity indicators differed significantly by gender and age. The TC level was positively associated with obesity indicators in boys of all ages ( β BMI =0.01, β FMI =0.03, β BRI = 0.08 , and β WHtR =0.16) but only with FMI, BRI, and WHtR in girls 6-9 years of age ( β FMI =0.02, β BRI =0.05, and β WHtR =0.08) (all P <0.05). The RC level had a negative correlation with BRI in boys 10-17 years of age ( β =-0.01) and a positive correlation with BMI in girls 6- 9 years of age ( β =0.00) (all P <0.05). Logistic regression indicated that elevated obesity indicators were significantly associated with higher risks of elevated TG, LDL-C, and non HDL-C levels and a decreased HDL-C level in all gender age stratas (all P <0.01). Only the BMI and FMI in girls 6-9 years of age were significantly related to a high RC ( OR =1.07, 1.07, both P <0.05). ROC analysis revealed that FMI, BRI, and WHtR were more predictive than BMI of elevated TG, LDL-C, and non HDL-C levels. The BMI was superior in predicting a decreased HDL-C level in boys, while no significant difference was detected among indicators in girls. Indeed, all obesity indicators had poor predictive performance for elevated TC, RC, and LDL-C levels in girls (all AUC<0.7). Conclusions Obesity indicators reflecting body fat content and fat distribution are shown to be closely associated with dyslipidemia in children and adolescents with obvious age and gender differences. The FMI, BRI, and WHtR have potential advantages in the early identification of dyslipidemia among children and adolescents compared to the BMI alone.

Objective:To establish an arsenic free fully automatic online digestion iodine analyzer detection method for urinary iodine (hereinafter referred to as the method).Methods:Based on the principle of iodine catalyzed antimony cerium redox reaction, a fully automatic online digestion iodine analyzer was used to determine the iodine content in urine. The effectiveness of the method in terms of detection limit, precision, accuracy (determination of urinary iodine primary standard reference materials GBW09108z and GBW09110f and spiked recovery experiment), and interference experiments was validated. The method was compared with the arsenic cerium catalytic spectrophotometry method recommended by the National Reference Laboratory for Iodine Deficiency Disorders.Results:The linear range of the method was 0 - 300 μg/L, with a correlation coefficient │ r│> 0.999 5. The qualitative and quantitative detection limits were 7.41 and 18.01 μg/L, respectively. The relative standard deviation ( RSD) of urine samples with different iodine concentrations ranged from 1.0% to 1.7%. The results of the determination of iodine concentrations in urine using standard substances GBW09108z and GBW09110f were within the given standard range, with RSD < 2.5%. The range of spiked recovery rates for urine samples with different iodine concentrations was 101.3% to 104.8%, with an overall average spiked recovery rate of 103.0%. The average concentration of the baseline iodine standard solution was determined to be 116.21 μg/L, and the relative error of the concentration determination with the addition of interfering substances was less than 5.0%. The comparison results showed that there was no statistically significant difference in the measurement results between the two methods ( t = - 0.06, P = 0.952). Conclusions:The method adopts automated detection, which is simple to operate, labor-saving, and does not require the use of arsenic trioxide. It has high precision and accuracy, and is suitable for detection of large quantities of samples.

Objective:To analyze the clinical and prognostic characteristics of patients with immune checkpoint inhibitor (ICI) -related colitis.Methods:A retrospective observational research method was conducted. Clinical data from patients diagnosed with ICI-related colitis at Beijing Friendship Hospital between January 2016 and May 2024 were collected. Clinical severity was assessed using the common terminology criteria for adverse event (CTCAE) grading, Mayo Score, Truelove & Witts Score, and endoscopic severity was assessed using Mayo endoscopic score (MES), ulcerative colitis endoscopic index of severity (UCEIS), and MD Anderson Cancer Center endoscopic inflammation grading (MD grading). Spearman rank correlation analysis was performed to evaluate the correlation between different scoring systems.Results:A total of 15 patients were included, with 10 males and 5 females, and the median age was 64.0 (55.5, 71.0) years. Thirteen patients were treated with programmed cell death protein 1 (PD-1) monoclonal antibodies, and 2 patients were treated with programmed cell death-ligand 1 (PD-L1) monoclonal antibodies. The median onset time of the 15 patients was 66.5 (41.0, 168.0) days after ICI treatment. All patients had diarrhea, only 25% patients presented with abdominal pain, and 20%-33% patients had fever, abdominal distension, nausea, and vomiting. Most of the inflammatory indicators were non-specific. Among the 14 patients who underwent CT examinations, 2 patients had no abnormal manifestations, 10 patients had left colon involvement, mainly manifested as thickening of the colon wall, and 6 of these patients had full-thickness involvement. Among the 12 patients who underwent colonoscopy examination, except for one patient with no abnormalities, 11 patients had rectal and sigmoid colon involvement, the proportions of the descending colon, ascending colon, and terminal ileum involvement decreased successively, and the involved mucosa was mainly manifested as disappearance of vascular texture, mucosal congestion and edema, erosion to shallow ulcers, and lumen stenosis. The lesions in 5 patients were distributed continuously similar to ulcerative colitis, and the lesions in 6 patients were distributed segmentally, 1 of them had an isolated deep ulcer in the rectum under endoscopy. Correlation analysis revealed significant correlations between endoscopic scores (MES, UCEIS, and MD grading; all P < 0.001). Truelove & Witts score strongly correlated with the Mayo score ( ρ = 0.88, P < 0.001). Among clinical-endoscopic comparisons, the Mayo score exhibited the strong positive correlation with endoscopic scores (all P < 0.05), followed by the Truelove & Witts score (all P < 0.05), and CTCAE diarrhea grading only had positive correlation with MD grading ( P = 0.034). However, CTCAE colitis grading showed no significant correlation with endoscopic scores (all P > 0.05). During a mean follow-up of 13.5 months, 10 patients received corticosteroid therapy, and 5 received alternative treatments. Corticosteroid-treated patients showed favorable clinical responses, and rapid tapering feasible occurred in parts of mild-to-moderate patients without relapse. However, perforation occurred in 2 patients with small bowel involvement. Conclusions:The main clinical manifestations of patients with ICI-related colitis are diarrhea. Imaging studies suggest thickening of the colonic wall. Endoscopic findings show the highest involvement in the left colon. Truelove&Witts score and Mayo score is strongly correlated. Corticosteroid therapy exhibits a rapid response, and the prognosis of patients with small intestine involvement is poor.

Objective:To analyze the clinical characteristics and cytokines expression characteristics in infants with mild and severe respiratory syncytial virus (RSV) infection.Methods:From May 2023 to December 2023, plasma samples and clinical information were collected from 16 infants with RSV infection and 14 control infants. Cytek Aurora flow cytometry (Cytek, America) and Enzyme linked immunosorbent assay (ELISA) were used to detect the expression levels of 25 cytokines after mild and severe RSV infection.Results:Cough and nasal obstruction were the main clinical manifestations in infants with mild RSV infection, accompanied by polypnea, wheezing and other symptoms. The main symptoms of severe RSV infection were cough and rales, accompanied by fever and polypnea. In comparison with the control group, the expression levels of IL-2, IL-4, IL-5, IL-6, IL-9, IL-13, IL-22, TNF-α, IFN-α, IFN-β, MIP-1β, I-TAC, ENA-78, GROα, Eotaxin, and MCP-1 in the RSV infection group all exhibited an upregulation trend. Both IP-10 and MIP-3α demonstrated a downward trend in the RSV infection group; however, there was no statistically significant difference ( P>0.05). The levels of IL-10, IFN-γ, MIP-1α, and IL-8 in the RSV infection group were significantly higher than those in the control group, whereas the levels of MIG, TARC, and RANTES in the RSV infection group were significantly lower than those in the control group ( P<0.05). The levels of IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-22, IFN-β, IFN-γ, TNF-α, IL-8, I-TAC, MIP-1β, Eotaxin, and MCP-1 in the mild RSV infection group were significantly higher than those in the severe RSV infection group ( P>0.05). Among these, the levels of MIG, RANTES, TARC, MIP-3α, and ENA-78 in the mild infection group were all lower than those in the severe infection group. The expressions of ENA-78 and MIP-1α in the severe infection group were significantly higher than those in the mild infection group and also higher than those in the control group. There was no significant difference in IP-10 and GROα between the mild and severe RSV infection groups ( P>0.05). Conclusions:The differences in clinical features and cytokines between infants with mild and severe RSV infection provide important data support for the prevention and treatment of RSV infection in infants.

OBJECTIVE T o assess the in vitro antimicrobial activity of aztreonam-avibactam against metallo-β—lacta-mase(MBL)-producing carbapenem-resistant Enterobacteriaceae(CRE)using different antimicrobial susceptibility testing methods,evaluate the consistency of results based on the latest breakpoints recommended by European Committee on Antimicrobial Susceptibility Testing(EUCAST),and analyze the clinical applicability.METHODS The imipenem-or meropenem-resistant Enterobacteriaceae strains were isolated from the clinical specimens of Bei-jing Chaoyang Hospital from Jan.2019 to Mar.2023,MBL-producing CRE were selected after they were con-firmed by colloidal gold immunoassay and Sanger sequencing as the study subjects.The minimum inhibitory con-centrations(MICs)of single aztreonam and aztreonam-avibactam compounds were determined by using broth mi-crodilution method.In addition,the disk diffusion method and the gradient diffusion method were employed to further detect the in vitro susceptibility to aztreonam-avibactam.RESULTS Among the 87 strains of MBL-producing CRE that were included in the study,Escherichia coli was the most common species,accounting for 44.83％.NDM-5 was the predominant carbapenemase type,detected in 48.28％of the isolates.According to the latest EUCAST break-points,6 isolates were aztreonam-avibactam-resistant strains based on broth microdilution method,all of which were E.coli,and the resistance rate was 6.90％(6/87).However,the resistance rate that was determined by the disk diffu-sion method was significantly higher(22.99％,20/87).Among these,14 strains was within the area of technical uncer-tainty/resistant,making result interpretation difficult.In addition,the categorical agreement between the gradient diffu-sion method and the broth microdilution method reached up to 98.85％.CONCLUSIONS Aztreonam-avibactam has high antimicrobial activity against MBL-producing CRE.However,based on the latest EUCAST breakpoints,the antimicrobial susceptibility testing by the disk diffusion method results of some strains are hard to interpret.It is necessary to integrate with other methods for further validation.

A subset of patients with multiple myeloma(MM)present with reduced serum vitamin B12 levels at initial diagnosis;however,its clinical significance and underlying mechanisms remain unclear.Vitamin B12 plays a crucial role in hematopoiesis and immune regulation.This study aims to elucidate its association with extramedullary diseases,immune function,and prognosis in MM patients.A retrospec-tive analysis was conducted of 92 newly diagnosed MM patients,who received treatment at the Second Af-filiated Hospital of Soochow University between January 2020 and December 2023.Patients were classi-fied into a low vitamin B12 group(n=37)and a normal vitamin B12 group(n=55)based on their ser-um vitamin B12 levels.The findings revealed that the incidence of extramedullary infiltration was signifi-cantly higher in the low vitamin B12 group than in the normal group(26.5％vs.17.0％,P=0.031).Survival analysis demonstrated that patients with low vitamin B12 levels had significantly shorter overall survival(OS)and progression-free survival(PFS)(OS:P=0.0123;PFS:P=0.0136).Additionally,these patients showed a decreasing trend in peripheral blood total T cell,CD4+T cell,and CD8+T cell counts,with serum vitamin B12 levels showing a significant positive correlation with the total T cell count(R=0.2717,P=0.0135)and CD4+T cell count(R=0.2175,P=0.0497).In conclusion,reduced serum vitamin B12 levels at initial diagnosis are significantly associated with poor prognosis in MM pa-tients and may serve as a potential prognostic biomarker.Furthermore,vitamin B12 deficiency may con-tribute to immune dysfunction,particularly impaired T cell immunity,and a higher incidence of extr-amedullary diseases.

Objective To study the clinical efficacy of buccal acupuncture in the treatment of refractory tinnitus in the elderly.Methods In this study,50 elderly patients with refractory tinnitus were randomly divided into two groups:the experimental group(n=26)received buccal acupuncture therapy on the neck,upper neck,scapula zone,shoulder,back,mastoid process,thoracic plexus,abdominal plexus and pelvic plexus on the affected side,and the control group(n=24)received sound therapy.After 8 weeks of treatment intervention,the two groups were comprehensively evaluated for the changes in the tinnitus evaluation scale(TEQ),self-rating depression scale(SDS),and blood rheological indexes,including whole blood high-cut viscosity(HSV),plasma viscosity(PSV)and fibrinogen in blood(FIB)clotting.Results After treatment,the total effective rate of the experimental group was 84.6％(22/26),higher than 54.2％(13/24)in the con-trol group.The difference in total effective rate and efficacy level between the two groups was statistically significant(P＜0.05).TEQ and SDS were significantly lower in the two groups compared to pre-treatment(P＜0.05),and HSV,PSV and FIB in the experimental group were significantly lower compared to pre-treatment(P＜0.05).The experimental group demonstrated better post-treatment outcomes in TEQ,SDS,HSV,and FIB compared to the control group(P＜0.05).Conclusion Buccal acupuncture treatment is effective in improving the symptoms of refractory tinnitus in the elderly,relie-ving the depression complicated by tinnitus,and is helpful in changing blood flow resistance and reducing blood coagulation probably.

Natural human leukocyte antigen (HLA) antibodies refer to preformed antibodies present in the body that are not induced by prior exposure to allogeneic HLA antigens. In healthy individuals without a sensitization history, the detection rate of natural HLA antibodies is approximately 20%-29% when using screening assays with low sensitivity, and can reach up to 63% when more sensitive HLA-specific detection methods are employed. It is therefore inferred that natural HLA antibodies may also be present in transplant candidates with a similar prevalence. This review comprehensively discusses the potential mechanisms of natural HLA antibody generation, the characteristics of the recognized epitopes, detection techniques, clinical relevance in transplantation, their potential to confound therapeutic decisions, and approaches to distinguish and mitigate their impact. The goal is to raise clinician awareness of the objective existence of natural HLA antibodies, provide guidance on evaluating their association with allograft rejection, and inform appropriate clinical management strategies when encountering natural HLA antibody-positive transplant candidates.