ObjectiveTo analyze the epidemiological characteristics and trends of hand-foot-mouth disease (HFMD) in Hangzhou, so as to provide an evidence for developing effective prevention and control measures and evaluating the control effects. MethodsThe incidence data of HFMD in Hangzhou were collected from the Infectious Disease Reporting Information Management System of China Information System for Disease Control and Prevention. Descriptive epidemiology was applied to analyze the temporal, spatial and demographic distribution characteristics and etiology monitoring results of HFMD cases in Hangzhou from 2010 to 2023. Joinpoint regression model was used to analyze the trends of incidence rate of HFMD. Furthermore, circular distribution method was utilized to calculate the incidence peak of HFMD. ResultsFrom 2010 to 2023, the average annual reported incidence rate of HFMD in Hangzhou was 138.85/100 000, the proportion of severe cases was 0.04%, the mortality rate was 0.01/100 000, and the case fatality rate was 5.30/100 000. Both the total incidence rate and the incidence rate by sex showed an increasing trend. The annual reported incidence rate in males (158.72/100 000) was higher than that in females (117.61/100 000). The reported incidence rate showed a significant seasonal characteristic, with summer being the peak of epidemic. The results of surveillance samples suggested that the prevalence of HFMD in Hangzhou is characterized by the co-existence of multiple pathogens, with EV-A71 and CV-A16 being the dominant pathogens in the previous years and CV-A6 being the dominant pathogen since 2018. The proportion of EV-A71 in severe cases (77.19%) was higher than that in ordinary cases (15.37%), in addition, its proportion in ordinary cases, severe cases, and fatal cases all showed a decreasing trend. ConclusionThe incidence rate of HFMD in Hangzhou is still high, so it’s still necessary to continue to strengthen the prevention and control measures for key populations. In recent years, CV-A6 has been the main prevalent pathogen in Hangzhou. Further efforts in pathogen detection and analysis should be enhanced in the future.

This study aimed to explore the therapeutic mechanisms of Colquhounia Root Tablets(CRT) in treating diabetic kidney disease(DKD) by integrating biomolecular network mining with animal model verification. By analyzing clinical transcriptomics data, an interaction network was constructed between candidate targets of CRT and DKD-related genes. Based on the topological eigenvalues of network nodes, 101 core network targets of CRT against DKD were identified. These targets were found to be closely related to multiple pathways associated with type 2 diabetes, immune response, and metabolic reprogramming. Given that immune-inflammatory imbalance driven by metabolic reprogramming is one of the key pathogenic mechanisms of DKD, and that many core network targets of CRT are involved in this pathological process, receptor for advanced glycation end products(RAGE)-reactive oxygen species(ROS)-phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)-nuclear factor-κB(NF-κB)-NOD-like receptor family pyrin domain containing 3(NLRP3) signaling axis was selected as a candidate target for in-depth research. Further, a rat model of DKD induced by a high-sugar, high-fat diet and streptozotocin was established to evaluate the pharmacological effects of CRT and verify the expression of related targets. The experimental results showed that CRT could effectively correct metabolic disturbances in DKD, restore immune-inflammatory balance, and improve renal function and its pathological changes by inhibiting the activation of the RAGE-ROS-PI3K-AKT-NF-κB-NLRP3 signaling axis. In conclusion, this study reveals that CRT alleviates the progression of DKD through dual regulation of metabolic reprogramming and immune-inflammatory responses, providing strong experimental evidence for its clinical application in DKD.
Animals ; Diabetic Nephropathies/metabolism* ; Receptor for Advanced Glycation End Products/genetics* ; NF-kappa B/genetics* ; Signal Transduction/drug effects* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species/metabolism* ; Humans ; Plant Roots/chemistry* ; Rats, Sprague-Dawley ; Tablets/administration & dosage*

OBJECTIVE: To investigate the effects of low-dose irradiated autologous peripheral blood reinfusion (LDIAPBR) on a rat model of radiation-induced leukopenia. METHODS: The rats were randomly divided into four groups. In the LDIAPBR group, LDIAPBR was performed 1 day before modeling (10% of the total circulating blood volume was withdrawn, irradiated with 100 mGy ex vivo, and completely reinfused). Meanwhile, the normal group and model group only underwent blood withdrawal and reinfusion of the same proportion without blood irradiation. Except for the normal group, all groups were subjected to 1 Gy X-ray whole-body irradiation to establish a radiation-induced leukopenia rat model. The positive drug group received subcutaneous injection of rhG-CSF after modeling. It was monitored that the general condition of the rats, peripheral blood cell counts, immune organ indices, bone marrow nucleated cell counts and viability, and the pathological analysis of bone marrow sections was conducted. RESULTS: The LDIAPBR group exhibited significant improvements in overall condition compared to the model group. Notably, compared with the model group, peripheral blood leukocyte and lymphocyte counts were markedly higher in the LDIAPBR group. Furthermore, there was a significant increase in both the number and viability of nucleated cells in the bone marrow. Pathological examination of bone marrow sections revealed increased nucleated cell density and reduced cavity area in the LDIAPBR group. CONCLUSION LDIAPBR can effectively improve hematological parameters and bone marrow hematopoietic function in a rat model of radiation-induced leukopenia, providing a new approach for the prevention and treatment of radiation-related injuries.
Animals ; Leukopenia/prevention & control* ; Rats ; Blood Transfusion, Autologous ; Whole-Body Irradiation ; Radiation Injuries, Experimental/therapy*

BACKGROUND: Children's respiratory health demonstrates particular sensitivity to air pollution. Existing evidence investigating the association between short-term ozone (O₃) exposure and childhood pneumonia remains insufficient and inconsistent, especially in low- and middle-income countries (LMICs). METHOD: To provide more reliable and persuasive evidence, we implemented a multi-city, time-stratified case-crossover design with a large sample size, using data from seven representative children's hospitals across major geographical regions in China. To avoid the impact of the COVID-19 pandemic, individual-level medical records of inpatient children under 6 years of age diagnosed with pneumonia during 2016-2019 were collected. Conditional logistic regression models were fitted for each city, and city-specific estimates were pooled through a meta-analysis using a random-effects model. RESULTS: In total, the study included 137,470 pediatric pneumonia hospital admissions. The highest pooled estimate for O₃ occurred at lag0-1, with a 10 µg/m³ increase in O₃ associated with a 1.57% (95% CI: 0.67%-2.48%) higher risk of pediatric pneumonia hospital admissions. Stratified analyses indicated that the effects of O₃ were robust across different sexes, age groups, and admission seasons. We also observed a statistically significant increase in risk associated with O₃ concentrations exceeding the World Health Organization Air Quality Guidelines (WHO-AQGs). CONCLUSIONS This study revealed a significant positive association between O₃ and pediatric pneumonia hospital admissions. Our findings substantially strengthen the evidence base for the adverse health impacts of O₃, underscoring the importance of O₃ pollution control and management in reducing the public health burden of pediatric pneumonia.
Humans ; Ozone/analysis* ; China/epidemiology* ; Pneumonia/chemically induced* ; Child, Preschool ; Male ; Female ; Infant ; Cross-Over Studies ; Air Pollutants/analysis* ; Hospitalization/statistics & numerical data* ; Child ; Cities/epidemiology* ; Air Pollution/adverse effects* ; Infant, Newborn ; Environmental Exposure/adverse effects*

Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

OBJECTIVE: This study aimed to investigate the impact of glycemic control and diabetes duration on subsequent myocardial infarction (MI) in patients with both coronary heart disease (CHD) and type 2 diabetes (T2D). METHODS: We conducted a retrospective cohort study of 33,238 patients with both CHD and T2D in Shenzhen, China. Patients were categorized into 6 groups based on baseline fasting plasma glucose (FPG) levels and diabetes duration (from the date of diabetes diagnosis to the baseline date) to examine their combined effects on subsequent MI. Cox proportional hazards regression models were used, with further stratification by age, sex, and comorbidities to assess potential interactions. RESULTS: Over a median follow-up of 2.4 years, 2,110 patients experienced MI. Compared to those with optimal glycemic control (FPG < 6.1 mmol/L) and shorter diabetes duration (< 10 years), the fully-adjusted hazard ratio ( HR) (95% Confidence Interval [95% CI]) for those with a diabetes duration of ≥ 10 years and FPG > 8.0 mmol/L was 1.93 (95% CI: 1.59, 2.36). The combined effects of FPG and diabetes duration on MI were largely similar across different age, sex, and comorbidity groups, although the excess risk of MI associated with long-term diabetes appeared to be more pronounced among those with atrial fibrillation. CONCLUSION Our study indicates that glycemic control and diabetes duration significant influence the subsequent occurrence of MI in patients with both CHD and T2D. Tailored management strategies emphasizing strict glycemic control may be particularly beneficial for patients with longer diabetes duration and atrial fibrillation.
Humans ; Diabetes Mellitus, Type 2/blood* ; Male ; Female ; Middle Aged ; Aged ; Coronary Disease/complications* ; Myocardial Infarction/etiology* ; Retrospective Studies ; China/epidemiology* ; Glycemic Control ; Blood Glucose ; Adult ; Risk Factors ; Time Factors

OBJECTIVE: To determine the prevalence of lumbar spondylolysis (LS) and the proportion of spondylolytic spondylolisthesis (SS) in China, and to evaluate the musculoskeletal status of patients with LS and SS. METHODS: Spine Computed Tomography (CT) images were collected from community populations aged 40 and above in a nationwide multi-center project. LS was diagnosed, and SS was graded by an experienced radiologist. Bone mineral density (BMD) and paraspinal muscle parameters were quantified based on CT images. RESULTS: One hundred and seventeen patients of a total of 3,317 individuals were diagnosed with LS, corresponding to a prevalence rate of 3.53%. 63 of the 1,214 males (5.18%) and 54 of the 2,103 females (2.57%) were diagnosed with LS. SS occurred in 64/121 vertebrae (52.89%). BMD was not associated with LS ( P = 0.341). The L5 extensor paraspinal muscle density was higher in the LS group than in the non-LS group. In the LS group, patients with SS had a smaller L5 paraspinal extensor muscle cross-sectional area than those without SS ( P = 0.003). CONCLUSION The prevalence of LS in Chinese adults was 3.53%, with prevalence rates of 5.18% in males and 2.57% in females. Patients with LS have higher muscle density, whereas those with SS have smaller muscle cross-sectional areas at the L5 level.
Humans ; Male ; Female ; Middle Aged ; China/epidemiology* ; Prevalence ; Adult ; Lumbar Vertebrae/diagnostic imaging* ; Spondylolysis/diagnostic imaging* ; Aged ; Bone Density ; Tomography, X-Ray Computed ; Aged, 80 and over ; Spondylolisthesis/epidemiology* ; East Asian People

ObjectiveTo investigate the therapeutic effect of Baihe Wuyaotang （BWT） on non-alcoholic fatty liver disease （NAFLD） and elucidate its underlying mechanism. MethodC57BL/6J mice were randomly assigned to six groups： normal control， model， positive drug （pioglitazone hydrochloride 1.95×10^-3 g·kg^-1）， and low-， medium-， and high-dose BWT （1.3，2.5 and 5.1 g·kg^-1）. Following a 12-week high-fat diet （HFD） inducement， the mice underwent six weeks of therapeutic intervention with twice-daily drug administration. Body weight was monitored weekly throughout the treatment period. At the fifth week， glucose tolerance （GTT） and insulin tolerance （ITT） tests were conducted. Subsequently， the mice were euthanized for the collection of liver tissue and serum， and the subcutaneous adipose tissue （iWAT） and epididymal adipose tissue （eWAT） were weighed. Serum levels of total triglycerides （TG） and liver function indicators，such as alanine aminotransferase （ALT） and aspartate aminotransferase （AST）， were determined. Histological examinations， including oil red O staining， hematoxylin-eosin （HE） staining， Masson staining， and transmission electron microscopy， were performed to evaluate hepatic lipid deposition， pathological morphology， and ultrastructural changes， respectively. Meanwhile， Western blot and real-time quantitative polymerase chain reaction （Real-time PCR） were employed to analyze alterations， at both gene and protein levels， the insulin signaling pathway molecules， including insulin receptor substrate 1/2/protein kinase B/forkhead box gene O1 （IRS1/2/Akt/FoxO1）， glycogen synthesis enzymes phosphoenolpyruvate carboxy kinase （Pepck） and glucose-6-phosphatase （G6Pase）， lipid metabolism-related genes stearoyl-coA desaturase-1 （SCD-1） and carnitine palmitoyltransferase-1 （CPT-1）， fibrosis-associated molecules α-smooth muscle actin （α-SMA）， type Ⅰ collagen （CollagenⅠ）， and the fibrosis canonical signaling pathway transforming growth factor-β₁/drosophila mothers against decapentaplegic protein2/3（TGF-β₁/p-Smad/Smad2/3）， inflammatory factors such as interleukin（IL）-6， IL-8， IL-11， and IL-1β， autophagy markers LC3B Ⅱ/Ⅰ and p62/SQSTM1， and the expression of mammalian target of rapamycin （mTOR）. ResultCompared with the model group， BWT reduced the body weight and liver weight of NAFLD mice（P<0.05， P<0.01）， inhibited liver lipid accumulation， and reduced the weight of white fat： it reduced the weight of eWAT and iWAT（P<0.05， P<0.01） as well as the serum TG content（P<0.05， P<0.01）. BWT improved the liver function as reflected by the reduced ALT and AST content（P<0.05， P<0.01）. It improved liver insulin resistance by upregulating IRS2， p-Akt/Akt， p-FoxO1/FoxO1 expressions（P<0.05）. Besides， it improved glucose and lipid metabolism disorders： it reduced fasting blood glucose and postprandial blood glucose（P<0.05， P<0.01）， improved GTT and ITT（P<0.05， P<0.01）， reduced the expression of Pepck， G6Pase， and SCD-1（P<0.01）， and increased the expression of CPT-1（P<0.01）. The expressions of α-SMA， Collagen1， and TGF-β₁ proteins were down-regulated（P<0.05， P<0.01）， while the expression of p-Smad/Smad2/3 was downregulated（P<0.05）， suggesting BWT reduced liver fibrosis. BWT inhibited inflammation-related factors as it reduced the gene expression of IL-6， IL-8， IL-11 and IL-1β（P<0.01） and it enhanced autophagy by upregulating LC3B Ⅱ/Ⅰ expression（P<0.05）while downregulating the expression of p62/SQSTM1 and mTOR（P<0.05）. ConclusionBWT ameliorates NAFLD by multifaceted improvements， including improving IR and glucose and lipid metabolism， anti-inflammation， anti-fibrosis， and enhancing autophagy. In particular， BWT may enhance liver autophagy by inhibiting the mTOR-mediated signaling pathway.

ObjectiveTo explore the molecular mechanism of Sanhuang Xiexintang （SHXXT） in protecting stress gastric ulcer （SGU） in rats through network pharmacology， molecular docking， and animal experiments. MethodThe active ingredients and corresponding targets in SHXXT were collected and screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， Traditional Chinese Medicine Information Database （TCMID）， Bioinformation Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）， and Swiss Target Prediction database. SGU-related targets were screened from the Online Mendelian Inheritance in Man （OMIM）， Therapeutic Target Database （TTD）， GeneCards database， and PharmGKB database. Herbal-ingredient-target （H-C-T） network was constructed by using Cytoscape 3.9.1 software. Protein-protein interaction （PPI） of drug and disease intersection targets was analyzed by using the Protein Interaction Platform （STRING） database. Gene ontology （GO） enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis were conducted through the Database for Annotation Visualization and Integrated Discovery （DAVID）. The active ingredients and key targets were validated using AutodockVina 1.2.2 molecular docking software， and the experimental results were further validated through animal experiments. ResultThe 55 active ingredients were screened， and 255 potential target genes for SHXXT treatment of SGU were predicted. The PPI analysis showed that protein kinase B （Akt）， phosphatase and tensin homolog deleted on chromosome ten （PTEN）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and cyclooxygenase-2 （COX-2） are the core targets of SHXXT for protecting SGU. GO and KEGG analyses showed that SHXXT may affect the development of SGU by regulating various biological processes such as the phosphoinositide 3-kinase （PI3K）/Akt signaling pathway and inflammatory processes. The molecular docking results showed that both the active ingredients and key targets had good binding ability. Animal experiments showed that compared with the blank group， the ulcer index （UI） of the model group was significantly increased （P<0.01）， and the serum levels of TNF-α and IL-1β significantly increased （P<0.01）. The phosphorylation level of PTEN in gastric mucosal tissue was significantly down-regulated （P<0.05）. The phosphorylation levels of PI3K， Akt， and nuclear factor kappa-B （NF-κB） were significantly up-regulated （P<0.05）. Compared with the model group， the UI of the treatment group was significantly reduced （P<0.01）， and the serum levels of TNF-α and IL-1β were significantly reduced （P<0.01）. The phosphorylation level of PTEN in gastric mucosal tissue was significantly up-regulated （P<0.01）， and the phosphorylation levels of PI3K， Akt， and NF-κB were significantly downregulated （P<0.01）. ConclusionThe application of network pharmacology prediction， molecular docking simulation， and animal experimental validation confirms that SHXXT regulates the PI3K/Akt/NF-κB signaling pathway to regulate the inflammatory response of rats and thus protects the gastric mucosa of SGU rats.

This article reports a patient with hepatic coma who underwent artificial liver support therapy and liver transplantation successfully， and the patient recovered well in the later stage after active treatment. This article also discusses the timing of liver transplantation.