Objective To investigate the effect of bone metabolic markers on sarcopenia in elderly patients with type 2 diabetes mellitus (T2DM). Methods A total of 412 patients with T2DM in the department of endocrinology of Nanjing Central Hospital from May 2020 to June 2025 were selected as the research subjects. According to Asian Working Group for Sarcopenia (AWGS) in 2019, these patients were evaluated for skeletal muscle mass index (ASMI), muscle strength, and muscle function, and were divided into a sarcopenia group (84 cases) and a non-sarcopenia group (328 cases). The glucolipid metabolic indexes were detected in both groups of patients, and the bone metabolic markers were evaluated, including procollagen type 1 N-terminal peptide (P1NP), beta-C-terminal telopeptide of type 1 collagen (β-CTX), and 25-hydroxy vitamin D [25-(OH)D]. The factors influencing the occurrence of sarcopenia in T2DM patients were analyzed by logistic regression analysis, and the diagnostic values of bone metabolic markers on sarcopenia in patients with T2DM were assessed by ROC curve. Results The levels of P1NP and 25-(OH)D were lower, while β-CTX level was higher in the sarcopenia group compared to the non-sarcopenia group, with statistical differences (P<0.05). After logistic correlation analysis, it was found that P1NP, β-CTX and 25-(OH)D were all influencing factors for the occurrence of sarcopenia in T2DM patients. ROC curve analysis suggested that combined detection of PINP, β-CTX, and 25-(OH)D had higher diagnostic value, with an area under the curve up to 0.805. Conclusion The abnormal expression of bone metabolic markers is associated with the increased risk of sarcopenia in patients with T2DM. The detection of serum bone metabolic markers expression level is of certain significance for the assessment of diabetes-related sarcopenia.

[摘 要] 目的：探讨绿茶单体表没食子儿茶素没食子酸酯（EGCG）对大鼠肝癌发生过程中肠道菌群结构变化的影响。方法：建立二乙基亚硝胺（DEN）诱导的肝癌大鼠模型。将26只SD大鼠随机分成3组，分别为正常对照组、肝癌组和EGCG干预组。从实验开始第1天起，EGCG干预组每日给予EGCG（40 mg/kg）灌胃，正常对照组和肝癌组给予等量生理盐水灌胃，1次/日，持续至第20周。灌胃结束后，采集大鼠粪便样本，提取DNA，进行高通量16S rRNA V3-V4区测序；处死大鼠，取肝，观察肿瘤形成情况，并计算肝癌发生率。对测序数据进行生物信息学分析：经质控、聚类获得操作分类单元（OTU）表，据此计算α多样性指数（包括Observed species、Chao1、Shannon和Simpson指数），并进行β多样性分析。同时，对物种进行分类学注释，比较各组间菌群组成与丰度差异。结果： EGCG干预组大鼠（8只）肝脏肿瘤形成率明显低于肝癌组（10只）（50% vs 100%， P = 0.023），正常对照组（8只）大鼠无肿瘤发生。在肠道菌群方面，肝癌组操作分类单元（OTU）数量远低于正常对照组（P <0.001），而EGCG干预组OTU数量总体上高于肝癌组（P = 0.021）。α多样性分析显示，肝癌组Shannon指数低于正常对照组（P < 0.05）；此外，与肝癌组相比，EGCG干预组的Observed species指数、Chao1指数、Shannon指数和Simpson指数均显著提高（P < 0.05）。β多样性分析及主坐标分析（PCoA）表明，三组肠道菌群结构存在显著分离（PERMANOVA， R² = 0.3918， P = 0.001），其中EGCG干预组群落结构介于肝癌组与正常对照组之间，并更接近于正常对照组。肝癌组大鼠较正常大鼠肠道菌群中链球菌等潜在致病菌富集，丁酸产生相关菌（如丁酸球菌属、瘤胃球菌属等）丰度显著降低（P < 0.05）。相比之下，在EGCG干预肝癌发生过程中，大鼠肠道菌群结构相对稳定。厚壁菌门/拟杆菌门比值较肝癌组显著提高（P < 0.05），益生菌（如双歧杆菌属、乳杆菌属等）和丁酸产生相关菌（如丁酸球菌属）富集。结论：EGCG干预可降低DEN诱导的大鼠肝癌发生率，并有助于稳定肠道菌群结构，其作用可能与增加菌群多样性、促进益生菌及丁酸产生菌富集、恢复菌群平衡有关。

Objective To investigate the incidence trends and influencing factors of non-alcoholic fatty liver disease (NAFLD) -related cirrhosis in China, predict future disease burden, and provide evidence for public health prevention strategies. Methods Based on the Global Burden of Disease (GBD) 2021 database, we employed joinpoint regression analysis to analyze NAFLD-related cirrhosis trends in China from 1990 to 2021, quantified influencing factors using age-period-cohort modeling, and predicted future incidence through Bayesian age-period-cohort analysis. Results The age-standardized incidence rates (ASIRs) of NAFLD-related cirrhosis showed a persistent increase from 1990 to 2021, with annual percentage changes (APCs) of 0.70% for male and 0.79% for female(both P<0.05). Age-effects revealed a U-shaped variation pattern, peaking in the 60-69 age group. Period effects indicated an incidence peak during 2017-2021. Cohort effects showed the most prominent risk in the 1992-1996 birth cohort. Projections suggested ASIR would further increase to 578.40 and 930.61 per 100 000 population for males and females, respectively, by 2030. Conclusions The disease burden of NAFLD-related cirrhosis continues to worsen in China, with future incidence rates projected to keep rising. Priority attention should be given to middle-aged and elderly populations and sex differences, with targeted prevention and control measures needing to be developed.

Gene therapy, harnessing the power of CRISPR-Cas9 and/or DNAzyme systems, stands as a pivotal approach in cancer therapy, enabling the meticulous manipulation of genes pivotal to tumorigenesis and immunity. However, the pursuit of precise gene therapy encounters formidable hurdles. Herein, a near-infrared upconversion theranostic nanomachine is devised and tailors for CRISPR-Cas9/DNAzyme systems mediate precise gene therapy. An ingenious logic DNAzyme system consists of Chain 1 (C1)/Chain 2 (C2) and endogenous lncRNA is designed. We employ manganese modified upconversion nanoparticles for carrying ultraviolet-responsive C1-PC linker-C2 (C₂P) chain and Cas9 ribonucleoprotein (RNP), with outermost coats with hyaluronic acid. Upon reaching tumor microenvironment (TME), the released Mn²⁺ ions orchestrate a trifecta: facilitating endosomal escape, activating cGAS-STING signaling, and enabling T1-magnetic resonance imaging. Under near-infrared irradiation, Cas9 RNP/C₂P complex dissociates, releasing Cas9 RNP into the nucleus to perform gene editing of Ptpn2, while C1/C2 chains self-assemble with endogenous lncRNA to form a functional DNAzyme system, targeting PD-L1 mRNA for gene silencing. This strategy remodels the TME by activating cGAS-STING signaling and dual immune checkpoints blockade, thus realizing tumor elimination. Our theranostic nanomachine armed with the CRISPR-Cas9/DNAzyme logic systems, represents a resourceful and promising strategy for advancing cancer systemic immunotherapy and precise gene therapy.

Objective:To analyze the genetic characteristics of coxsackievirus A16 (CVA16) related to hand, foot and mouth disease (HFMD) in Jiaxing from 2021 to 2023, and understand the biological and molecular evolutionary characteristics of CVA16 in this city.Methods:Real-time fluorescent quantitative PCR was used to detect enterovirus and its types in collected HFMD case samples. At the same time, virus isolation and cultivation were performed on positive samples using RD cells. Then high-throughput sequencing of the whole genome was performed on 23 strains of CVA16 identified from the isolated samples. Finally we obtained its whole genome sequence. DNAStar, MEGA 6.0, Simplot 3.5.1 and other bioinformatics software were used to compare and analyze the sequences, construct the phylogenetic tree of VP1 region, and realize the genotype composition. And these software were also used to analyze the homology of the whole genome nucleotide sequence and the encoded amino acids, while know well the amino acid mutation sites and gene recombination in the main regions.Results:The results showed that among the 1 836 HFMD specimens tested from 2021 to 2023, 1 432 (78.00%, 1 432/1 836) were positive for enterovirus general genes, of which 263 were positive for CVA16, accounting for 18.37% (263/1 432) of the confirmed positive cases. Twenty-three CVA16 strains were sequenced and all of them were B1 subtype, of which 6 strains belong to B1b and 17 strains belong to B1a, with B1a being dominant. B1a strains in Jiaxing showed genetic relatedness to strains isolated in Beijing, Yunnan, Guangzhou, Jiangsu and other places in 2018 to 2023, as well as strains from Vietnam, Thailand, and Australia from 2015 to 2017. B1b strains exhibited consistent amino acid mutations of L23M in the VP1 region and V217I in the VP2 region, while B1a strains exhibited amino acid mutations of S14N/D, T164K, and V251I in the VP1 region and R41H in the VP3 region. Compared with the prototype strain, the 23 strains of CVA16 in Jiaxing accumulated the largest number of amino acid mutations in the coding region, with 28 and 50 mutations in the VP1 and 3D regions, respectively. The recombination patterns of B1a and B1b strains were slightly different, with B1a type showing recombination with CVA8 in the 5′-UTR region instead of CVA4, B1a was similar to enterovirus A71 in most of P2 and P3 regions, and recombined with CVA5 in the 3D region of P3.Conclusions:The prevalent strain of CVA16 in Jiaxing may share a common trend of co-circulation and evolution with those in other provinces. The recombination mainly occurs in the 5′-UTR region and non-structural protein coding regions of P2 and P3. Continuous molecular surveillance of CVA16 is in need, and whole-genome sequencing can help understand the genetic variation, evolution, and recombination of strains.This information will provide a more robust basis for the monitoring and early warning, vaccine development, and prevention and control efforts against HFMD.

Non-inferiority clinical trials are a research paradigm that employs randomized controlled methods to evaluate whether the treatment effect of the experimental group is not inferior to that of the active control group within a predefined acceptable margin. This article systematically summarizes the applicable conditions, key design elements, and statistical analysis methods for non-inferiority trials. By integrating representative case studies in the field of oncology, it elucidates the unique value of non-inferiority designs in balancing benefits and risks and in optimizing therapeutic decisions. Through reviewing theoretical frameworks and addressing common misconceptions in methodological practices, this study aims to provide clear guidance for the standardized design and scientific interpretation of non-inferiority trials, thereby promoting their high-quality application in clinical research.

Objective:To predict the monthly incidence of hemorrhagic fever with renal syndrome (HFRS) in Hebei Province by using the generalized additive model (GAM).Methods:The incidence data of HFRS in Hebei from 2006 to 2020 were collected, and the correlation coefficients between meteorological factors and the monthly incidence of HFRS in Hebei were analyzed by Spearman's correlation, and the meteorological factors were lagged by 0-6 orders, and those with the largest absolute values of the correlation coefficients were screened to be included in the multifactorial GAM to evaluate the effects of meteorological factors.Results:The monthly incidence of HFRS had the strongest correlation with monthly mean air temperature at lag order 2, monthly mean wind speed at lag order 0, monthly mean sunshine at lag order 4, monthly mean precipitation at lag order 2 and monthly mean humidity at lag order 1, which were diagnosed by the variance inflation factor and included in the multifactorial GAM, and the results showed significant differences among the factors (all P<0.001), and they showed non-linear relationships with the monthly incidence of HFRS. Mean monthly temperature was an important factor influencing HFRS incidence. Mean monthly air temperature, mean monthly sunshine and mean monthly wind speed were negatively associated with HFRS incidence, whereas mean monthly precipitation and mean monthly humidity were positively associated with HFRS incidence. Conclusions:There was a complex non-linear relationship between meteorological factors and the incidence of HFRS. GAM incorporated with lagged meteorological factors can be used to predict the incidence of HFRS in Hebei.

Objective To explore the safety and effects of alpha-lipoic acid (ALA) in patients with ischemic heart failure (IHF). Methods A randomized, double-blind, placebo-controlled trial was designed (ClinicalTrial.gov registration number NCT03491969). From January 2019 to January 2023, 300 patients with IHF were enrolled in four medical centers in China, and were randomly assigned at a 1∶1 ratio to receive ALA (600 mg daily) or placebo on top of standard care for 24 months. The primary outcome was the composite outcome of hospitalization for heart failure (HF) or all-cause mortality events. The second outcome included non-fatal myocardial infarction (MI), non-fatal stroke, changes of left ventricular ejection fraction (LVEF) and 6-minute walking distance (6MWD) from baseline to 24 months after randomization. Results Finally, 138 patients of the ALA group and 139 patients of the placebo group attained the primary outcome. Hospitalization for HF or all-cause mortality events occurred in 32 patients (23.2%) of the ALA group and in 40 patients (28.8%) of the placebo group (HR＝0.753, 95%CI 0.473-1.198, P＝0.231; Figure 1A-1C). The absolute risk reduction (ARR) was 5.6%, the relative risk reduction (RRR) associated with ALA therapy was approximately 19.4% compared to placebo, corresponding to a number needed to treat (NNT) of 18 patients to prevent one event. In the secondary outcome analysis, the composite outcome of the major adverse cardiovascular events (MACE) including the hospitalization for HF, all-cause mortality events, non-fatal MI or non-fatal stroke occurred in 35 patients (25.4%) in the ALA group and 47 patients (33.8%) in the placebo group (HR＝0.685, 95%CI 0.442-1.062, P＝0.091; Figure 1D). Moreover, greater improvement in LVEF (β＝3.20, 95%CI 1.14-5.23, P＝0.002) and 6MWD (β＝31.7, 95%CI 8.3-54.7, P＝0.008) from baseline to 24 months after randomization were observed in the ALA group as compared to the placebo group. There were no differences in adverse events between the study groups. Conclusions These results show potential long-term beneficial effects of adding ALA to IHF patients. ALA could significantly improve LVEF and 6MWD compared to the placebo group in IHF patients.

Objective To investigate the impact of nutritional risk-based intervention on the quality of life and survival prognosis of patients with the locally advanced pancreatic cancer and undergoing the chemotherapy.Methods A total of 118 patients with the pancreatic cancer and admitted to the Department of Hepatobiliary and Minimally Invasive Surgery,Lincang People's Hospital from April 2021 to April 2024 were selected and randomly divided into the nutritional intervention group and the control group,with 59 patients in each group.All patients received the palliative chemotherapy,and the control group received the routine dietary guidance,while the intervention group received the nutritional intervention based on the nutritional risk score.The nutritional status,quality of life score,and survival prognosis of the two groups were compared.Results The NRS2002 score of the intervention group and the control group gradually increased from the first to the sixth chemotherapy,and the NRS2002 score of the intervention group was lower than that of the control group at the 4th,5th,and 6th chemotherapy(P<0.05).The incidence of malnutrition in the intervention group was lower than that of the control group at the 1st,2nd,and 3rd chemotherapy(11.9%,30.9%,and 32.2%,respectively),but there was no significant difference(P>0.05);The incidence of malnutrition in the intervention group was significantly lower than that of the control group at the 4th,5th,and 6th chemotherapy(32.2%,45.8%,and 52.5%,respectively),while the incidence of malnutrition in the control group was 59.3%,69.5%,and 88.5%,respectively(P<0.05);The quality of life score of the intervention group in all dimensions was significantly higher than that of the control group after the treatment(P<0.05).After the nutritional intervention,the median OS time and median PFS time of the patients were significantly improved(P<0.05).Conclusion Nutritional intervention can reduce the nutritional risk during the chemotherapy for locally advanced pancreatic cancer patients and improve their quality of life.

Objective To investigate the level and significance of serum suprabasin(SBSN)in patients with colorectal cancer(CRC).Methods A total of 200 patients with CRC in Nanjing Medical University Af-filiated Cancer Hospital from October 2023 to October 2024 were selected as the CRC group,200 patients with colorectal polyps were selected as the benign bowel disease(BCD)group,and 177 healthy people were selected as the control group.In addition,the serum SBSN levels of 84 CRC patients 7-10 d after surgery were collect-ed.The levels of SBSN in each group were compared,and the relationship between serum SBSN level and clin-icopathological characteristics of CRC patients was analyzed.Multivariate Logistic regression was used to ana-lyze the influencing factors of CRC.The receiver operating characteristic(ROC)curve was used to analyze the diagnostic efficacy of serum SBSN alone and in combination with carcinoembryonic antigen(CEA)and carbo-hydrate antigen 19-9(CA19-9)for CRC.Results The serum SBSN level in CRC group was significantly high-er than that in BCD group and control group(P＜0.001).Serum SBSN level in CRC patients was associated with TNM stage and lymph node metastasis(both P=0.001),but not with other clinicopathological features(P＞0.05).Serum SBSN,CEA,CA19-9 were independent risk factors for CRC(P＜0.001).ROC curve anal-ysis showed that the area under the curve(AUC)of SBSN alone in the diagnosis of CRC was 0.734,which was higher than that of CEA(0.611)and CA19-9(0.669)alone,and the AUC of the three combined diagno-sis of CRC was 0.816.The sensitivity and specificity were 70.0％and 81.4％,respectively.The serum SBSN level of CRC patients decreased after operation,and the difference was statistically significant compared with that before operation(P＜0.05).Conclusion SBSN is associated with the occurrence,metastasis and progno-sis of colorectal cancer,and has a certain clinical value in the diagnosis and prediction of colorectal cancer.Ser-um SBSN is a potential biomarker for the auxiliary diagnosis of colorectal cancer.