Objective To analyze the infection status and epidemic trends of soil-borne nematode infections in Yubei, Chongqing City, in 2010,2021, and 2022. Methods The local populations from four survey sites of four towns in 2010 and five sites of five towns in 2021 and 2022 were surveyed regarding their basic information using a unified form. Fecal samples of the participants were collected and tested for soil-borne nematode infections using the modified Kato-Katz thick smear method. Results In 2010, 2 049 participants were surveyed, followed by 1 000 participants in 2021 and 2022. The overall prevalence of parasitic infections declined significantly from 3.86% to 0.20%. In 2010, soil-transmitted nematode included hookworms(3.81%) and roundworms(0.29%). In 2021, the infection rates of roundworms and hookworms were 1.70% and 0.10% respectively. Notably, only Ascaris was identified in 2022(0.20%). The≥60 age group consistently exhibited the highest infection rates across all surveys, followed by the 40-59 age group. The infection rates of males in the three surveys were 3.31%,1.92%, and 0.20% respectively, and those of females were 4.37%, 1.46%, and 0.20% respectively. There was no statistically significant difference in the infection rates between males and females. Educational attainment was inversely associated with infection; in 2010, the highest prevalence was observed among those with primary education or below, whereas in 2021, illiterate or semi-literate individuals showed the highest susceptibility. The occupational distribution of infections in 2010 indicated that retirees (8.33%), farmers(4.86%), and homemakers or unemployed individuals(3.45%)were the most affected. However, in 2021 and 2022, farmers emerged as the predominant occupational group with soil-transmitted nematode infections. Conclusions The infection rate of soil-borne nematodes showed a decreasing trend in Yubei, and the infection species changed from hookworms in 2010 to Ascaris in 2022. Farmers, the elderly, and people with low education levels should continue to be the focus of preventive and control efforts.

Objective To analyze esophageal cancer burden trends in China from 1990 to 2021, further project the burden from 2022 to 2050. Methods The time trends of standardized incidence, standardized mortality, and standardized disability-adjusted life years (DALYs) rate of esophageal cancer in China from 1990 to 2021 using data from the Global Burden of Disease 2021 were analyzed using the estimated annual percentage change (EAPC). The disease burden of esophageal cancer in China from 2022 to 2050 was predicted using the Bayesian age–period–cohort model combined with sensitivity analysis and model calibration. Results In China, the ASIR of esophageal cancer increased from 17.637 per 10⁵ in 1990 to 22.548 per 10⁵ in 2021 (EAPC=0.55, 95%CI: 0.38–0.71). The ASMR rose from 17.920 per 10⁵ in 1990 to 20.836 per 10⁵ in 2021 (EAPC=0.21, 95%CI: 0.02–0.39). The age-standardized DALYs decreased from 497.437 per 10⁵ in 1990 to 484.884 per 10⁵ in 2021 (EAPC=−0.39, 95%CI: from −0.59 to −0.2). Among individuals aged 45 years and above, the proportion of esophageal cancer cases increased from 93.32% in 1990 to 97.56% in 2021, and the proportion of deaths in this age group rose from 90.44% in 1990 to 98.22% in 2021. For individuals aged 40 years and above, the proportion of DALYs attributed to esophageal cancer increased from 95.29% in 1990 to 98.29% in 2021. Among people aged 20 years and above, the incidence rate of esophageal cancer showed a downward trend in all age groups. In particular, the 35–39 year age group exhibited the most significant decline (EAPC=−3.74, 95%CI: from −4.22 to −3.25). Among individuals aged 20 years and above, the 70+ year age group had the smallest decrease in ASMR and age-standardized DALYs. By 2050, the standardized prevalence, standardized incidence, standardized mortality, and standardized DALY rate of esophageal cancer in China were predicted to decrease to 25.1/10⁵, 6.4/10⁵, 14.2/10⁵, and 12.0/10⁵, respectively. Conclusion From 1990 to 2021, the ASIR and ASMR of esophageal cancer in China showed an upward trend, whereas the age-standardized DALY rate exhibited a slow downward trend. Although the incidence of esophageal cancer showed a downward trend across all the age groups from 20 years and above, the overall standardized rate exhibited an upward trend due to factors such as population aging. By 2050, the burden of esophageal cancer in China, including prevalence, incidence, mortality, and DALYs, will decline. The population aged 45 years and above is the core group affected by esophageal cancer and should be prioritized for prevention and control.

Residual inflammatory risk （RIR） is a key issue to be urgently addressed in the secondary prevention of atherosclerotic cardiovascular disease （ASCVD）. Targeted intervention of RIR has become a novel target for drug development and clinical management. A series of high-quality randomized controlled trials （RCTs）， including COLCOT， LoDoCo2 and CLEAR SYNERGY， provided high-level evidence and confirmed that low-dose colchicine （0.5 mg/d） significantly reduced the risk of cardiovascular events in ASCVD patients at stable stage or after the acute phase， while its efficacy varied in different clinical scenarios. International authoritative guidelines from the European Society of Cardiology and the American Heart Association/American College of Cardiology include low-dose colchicine in the recommendations for ASCVD secondary prevention. Two domestic guidelines released in 2024， namely the Guideline for the Diagnosis and Treatment of Non-ST-Segment Elevation Acute Coronary Syndrome （ 2024 ） and the Guideline for the Diagnosis and Management of Chronic Coronary Syndrome in China ， have also added relevant recommendations. Nevertheless， due to potential racial differences， safety concerns regarding drug-drug interactions， and the relative lack of clinical evidence in China， especially the absence of prospective RCTs using low-dose colchicine for secondary prevention of ASCVD patients， current clinical recommendations still mainly based on international evidence and guidelines， and should not be simply extrapolated.

Objective: To examine the mediating effect of frailty on social isolation and cognitive function among the elderly. Methods: Demographic information, smoking, alcohol consumption and cognitive function of the elderly at ages of 60 years and older were collected from the China Health and Retirement Longitudinal Study 2020. Social isolation and frailty were evaluated using social isolation index and frailty index, respectively. The mediating effect of frailty on social isolation and cognitive function was analyzed using the Process program, and the significance of the mediating role was tested using the Bootstrap test. Results: A total of 2 822 individuals were enrolled, including 1 483 males (52.55%) and 1 339 females (47.45%). There were 2 497 (88.48%) and 325 (11.52%) individuals at ages of 60-<75 years and ≥75 years, respectively. The median cognitive function score was 14 (interquartile range, 16) points. There were 432 cases with social isolation (15.31%), with a median social isolation index of 10 (interquartile range, 5) points. The median frailty index was 0.11 (interquartile range, 0.15). There were 1 111 individuals without frailty, accounting for 39.37%; 1 214 individuals with pre-frailty, accounting for 43.02%; and 497 individuals with frailty, accounting for 17.61%. Mediating effect analysis showed that social isolation affected cognitive function directly and negatively with the effect value of -0.773 (95%CI: -0.899 to -0.647), and also affected cognitive function by frailty indirectly and negatively with the effect value of -0.147 (95%CI: -0.188 to -0.110), with the mediating effect contributed 15.98% of the total effect. Conclusion Frailty can directly or indirectly affect cognitive function among elderly through social isolation.

Objective The aim of this study was to characterize the basic molecular and biochemical parameters for a cyclophilin protein in Cryptosporidium parvum called CpCyP1.Methods CpCyP1 expression patterns during the parasite life cycle were evaluated using qRT-PCR with total RNA isolated from different developmental stages of C.parvum.Native CpCyP1 protein in sporozoites was detected using western blot.The localization of CpCyP1 was performed using the immunofluorescence assay,with an affinity-purified rabbit polyclonal antibody against a synthetic peptide.The peptidyl-prolyl cis-trans isomerase(PPIase)activity of His-tagged recombinant CpCyP1 was evaluated using absorbance colorimetry,and the effect of cyclosporin A(CsA)on the activity of CpCyP1 was determined.Results CpCyP1 was expressed in all parasite developmental stages,whereas CpCyP1 was present mainly in the cytosol of sporozoites,meronts,and gamonts.CpCyP1 displayed Michaelis-Menten kinetics towards N-succinyl-Ala-Ala-Pro-Phe-p-nitroanilide for its PPIase activity(Km=456.4 μmol/L;Vmax=1.981 U).CsA inhibited PPIase activity,showing lower micromolar inhibitory activity and binding affinity(Kd=5.122 μmol/L;IC50=1.004 μmol/L).Conclusions These results imply that CpCyP1 in the parasite may be the target for the previously reported anti-cryptosporidial efficacy of CsA and suggest that C.parvum cyclophilins could be evaluated as candidate drug targets.

OBJECTIVE: To analyze the carrier rates and profiles of pathogenic and likely pathogenic variants for hearing loss-related genes MYO7A, PCDH15, and CDH23 among neonates in Nanjing city through targeted next-generation sequencing (NGS). METHODS: Heel-prick blood samples were collected from 30 043 newborns delivered at Nanjing Women and Children's Health Care Hospital between March 2022 and April 2024. Dried blood spots were prepared, and genomic DNA was extracted. Targeted NGS was applied to detect variants across the full coding regions of the MYO7A, PCDH15, and CDH23 genes. The carrier rates and profiles of pathogenic and likely pathogenic variants of the three genes were analyzed. This study was approved by the Medical Ethics Committee of Nanjing Maternal and Child Health Care Hospital (Ethics No.: 2021KY-071). RESULTS: The carrier rates of pathogenic and likely pathogenic variants (with ≥ 1 variant site) for the MYO7A, PCDH15, and CDH23 genes were 0.340%, 0.226%, and 0.156%, respectively. A total of 65, 49, and 30 variant types were detected in the MYO7A, PCDH15, and CDH23 genes, respectively. For MYO7A, single base variants were predominant, with the most common variant being c.5581C>T, followed by c.1343+1G>A, c.2837T>G, and c.5660C>T, with allelic frequencies of 0.013% (8/60 086), 0.007% (4/60 086), 0.007% (4/60 086), and 0.007% (4/60 086), respectively. PCDH15 variants were mainly deletions, with the most common variant site being c.4699_4715dupAGAGAAAAGATTCAGAG, followed by c.3441delA, c.440T>G, and c.4733_4736delTCAG, with allelic frequencies of 0.015% (9/60 086), 0.005% (3/60 086), 0.005% (3/60 086), and 0.005% (3/60 086), respectively. For CDH23, single base variants were predominant, with c.6604G>A being the most common, followed by c.6085C>T, c.6050+9G>A, and c.6253+1G>A, with allelic frequencies of 0.013% (8/60 086), 0.012% (7/60 086), 0.005% (3/60 086), and 0.005% (3/60 086). CONCLUSION This study analyzed the carrier rates and profiles of pathogenic and likely pathogenic variants of the MYO7A, PCDH15, and CDH23 genes, which can provide more evidence for the prevention and management of deafness in the region.
Humans ; Cadherins/genetics* ; High-Throughput Nucleotide Sequencing/methods* ; Infant, Newborn ; Female ; Myosin VIIa/genetics* ; Cadherin Related Proteins ; Male ; Hearing Loss/genetics* ; Myosins/genetics* ; Heterozygote

Objective This study aimed to develop an automated method for syndrome element differenti-ation in Traditional Chinese Medicine(TCM).Methods We first constructed and trained an Instruction-tuned Multi-Task TCM text embedding model(Instr-MT-TCM)using four distinct TCM task datasets,including domain knowledge,synonymous terminology,syndrome differentiation and treatment,and TCM case labels.Subsequently,five TCM diagnostics experts holding master's degrees or higher were organized to screen a real-world TCM case dataset and annotate symptoms and signs.The purpose was to evaluate the F1-score of the proposed method—the combination of Instr-MT-TCM and a Large Language Model(LLM)—by comparing its performance against the manual annotation result on the syndrome element differentiation task.Finally,to validate its feasibility in real-world clinical settings,the method was applied to 48 prostate cancer cases to calculate the syndrome element scores.Results The Instr-MT-TCM model showed rapid performance improvement in its early training phase,achieving a Recall@1(R@1)of 0.848.Experts curated a dataset of 1,793 real-world clinical cases,covering 34 common diseases and 66 syndrome patterns.In the syndrome element differentiation task,the collaborative framework of LLM and Instr-MT-TCM achieved a mean F1-score of 0.927,outperforming the 0.512 from manual annota-tion.The syndrome element analysis revealed that the predominant elements of disease nature were fire(heat)and yin deficiency,while the main elements of disease location were bladder and kidney.Conclusion This study proposes and validates a novel method for automated TCM syndrome element dif-ferentiation based on the synergy between LLM and our custom Instr-MT-TCM model.Achieving a high F1-score(0.927)on real-world data,the method demonstrates excellent accuracy and generalization ability.Its application in prostate cancer analysis highlights its significant clinical potential,offering effective technical support,and a new research direction for intelligent TCM syndrome element differentiation.

Objective:To analyze the efficacy and safety of 3D-printing-assisted anterolateral thigh perforator flap surgery for the treatment of complex soft tissue defects around the ankle joint.Methods:A total of 160 patients with skin and soft tissue defects around the ankle joint at the First People′s Hospital of Xiaoshan District, Hangzhou, from March 2020 to March 2022 were retrospectively analyzed. The patients were divided into a control group and an observation group according to the surgical approach, with 80 patients in each group. The control group underwent traditional anterolateral thigh perforator flap surgery, which included 43 males and 37 females, with an age of 21-62 (34.7±5.6) years. The observation group underwent 3D-printing-assisted anterolateral thigh perforator flap surgery, which included 45 males and 35 females, with an age of 20-66 (34.8±5.6) years. The operative time, flap healing time, and hospital stay duration were compared between the two groups. Serum levels of C-reactive protein (CRP), interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF-α) were compared between the two groups before surgery and 3 days postoperatively. The ankle joint function was evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) scoring system, the range of motion (ROM) was assessed using the ROM score, and the flap sensation was evaluated using the modified Highet grading system before surgery, 6 months postoperatively, and at the last follow-up. The incidence of adverse reactions such as arterial crisis, venous crisis, infection, and necrosis during the perioperative period was observed. Patient satisfaction was assessed 6 months after treatment.Results:All patients in both groups successfully completed the surgery, with no cases excluded. The operative time, flap healing time, and hospital stay duration were significantly shorter in the observation group than those in the control group (all P<0.001). Compared with preoperative levels, the levels of IL-6, IL-8, CRP, and TNF-α were significantly reduced in both groups 3 days postoperatively (all P<0.001), and these levels were significantly lower in the observation group than those in the control group at 3 days postoperatively (all P<0.001). Six months postoperatively and at the last follow-up, the AOFAS and ROM scores were significantly higher in the observation group than those in the control group (all P<0.05), and the flap sensation grading was significantly better in the observation group than that in the control group (all P<0.05). The incidence of adverse reactions was 7.5% (6/80) in the observation group, which was significantly lower than 18.8% (15/80) in the control group ( P=0.024). The patient satisfaction rate was 95.0% (76/80) in the observation group, which was significantly higher than 72.5% (58/80) in the control group ( P<0.001). Conclusion:3D-printing-assisted anterolateral thigh perforator flap repair for skin and soft tissue defects around the ankle joint can improve perioperative indicators, reduce the incidence of postoperative adverse reactions, promote the recovery of flap sensation and ankle function, attenuate the inflammatory response of the body, and enhance patient satisfaction.

Solid-phase extraction(SPE)combined with surface-enhanced Raman spectroscopy(SERS)has emerged as a promising analytical technique for detection and analysis of trace components in complex sample matrices.SPE enriches analytes through selective adsorption and solvent elution,effectively increasing the concentration and signal intensity.SERS enables ultra-sensitive and highly selective molecular analysis through the use of SERS-active substrates engineered to amplify Raman signals.The integration of these two techniques overcomes the limitations of conventional Raman spectroscopy in low-concentration detection field,while significantly improving sample preparation efficiency and analytical accuracy.This review provided a comprehensive overview of the characteristics of three SPE-SERS coupling modes,including two-step,one-step,and online integration.Special emphasis was placed on recent advancements in one-step SPE-SERS approaches based on novel functional adsorbent materials such as graphene,metal-organic frameworks,covalent organic frameworks,and molecularly imprinted polymers.Furthermore,future directions and development prospects of SPE-SERS technology were discussed.

Andrographolide sulfonate (AS) is a sulfonated derivative of andrographolide extracted from Andrographis paniculata (Burm.f.) Nees, and has been approved for several decades in China. The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis. Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling, improved body weights, and attenuated pathological changes in joints of rats with adjuvant-induced arthritis. Additionally, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β in the serum and ankle joints were reduced. Bioinformatics analysis, along with the spleen index and measurements of IL-17 and IL-10 levels, suggested a potential relationship between AS and Th17 cells under arthritic conditions. In vitro, AS was shown to block Th17 cell differentiation, as evidenced by the reduced percentages of CD4⁺ IL-17A⁺ T cells and decreased expression levels of RORγt, IL-17A, IL-17F, IL-21, and IL-22, without affecting the cell viability and apoptosis. This effect was attributed to the limited glycolysis, as indicated by metabolomics analysis, reduced glucose uptake, and pH measurements. Further investigation revealed that AS might bind to hexokinase2 (HK2) to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or pyruvate kinase M2 (PKM2), and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation. Furthermore, AS impaired the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signals in vivo and in vitro, which was abolished by the addition of lactate. In conclusion, AS significantly improved adjuvant-induced arthritis (AIA) in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.
Animals ; Th17 Cells/immunology* ; Diterpenes/pharmacology* ; Arthritis, Rheumatoid/metabolism* ; Proto-Oncogene Proteins c-akt/immunology* ; Glycolysis/drug effects* ; Cell Differentiation/drug effects* ; Phosphatidylinositol 3-Kinases/genetics* ; Rats ; Male ; Rats, Sprague-Dawley ; Humans ; Andrographis paniculata/chemistry* ; Arthritis, Experimental/drug therapy* ; Interleukin-17/immunology* ; Signal Transduction/drug effects*