Objective: To investigate the association between childhood obesity and type 2 diabetes mellitus (T2DM) as well as coronary artery heart disease (CHD). Methods: Genome-wide association study (GWAS) data for childhood obesity were collected from the ECG consortium, encompassing information on children aged 2 to 18 years, including 18 613 cases and 12 696 controls. GWAS data for T2DM were collected from the DIAGRAM consortium, including 242 283 cases and 1 569 734 controls. GWAS data for CHD were collected from the CARDIoGRAMplusC4D consortium, including 10 801 cases and 137 371 controls. Pleiotropic genes associated with both T2DM and CHD were analyzed using the MAGMA, PLACO and conditional false discovery rate (cFDR) methods. Mendelian randomization (MR) analysis was performed using inverse variance weighted (IVW) method, exploring the causal relationships among childhood obesity, T2DM and CHD. Heterogeneity was evaluated using Cochran's Q test, horizontal pleiotropy and exclude outliers were tested using MR-Egger regression and MR-PRESSO test. The mediating variables among the three diseases were investigated by using a mediation analysis. Results: The results of MAGMA, PLACO and cFDR analyses identified 80 pleiotropic genes associated with both T2DM and CHD, primarily distributed on chromosomes 3, 17 and 19. The MR analysis revealed that childhood obesity increased the risk of T2DM (OR=1.151, 95%CI: 1.033-1.283) and CHD (OR=1.158, 95%CI: 1.068-1.255), T2DM increased the risk of CHD (OR=1.182, 95%CI: 1.139-1.227), and CHD increased the risk of T2DM (OR=1.124, 95%CI: 1.055-1.198). The MR-Egger regression analysis showed no horizontal pleiotropy, and the MR-PRESSO test did not identify any outliers (all P>0.05). Mediation analysis indicated that childhood obesity directly increased the risk of CHD (effect value=0.096, 95%CI: 0.012-0.180) and indirectly increased the risk of CHD through T2DM (effect value=0.023, 95%CI: 0.005-0.041), with the mediation effect accounting for 15.65% of the total effect. Conclusions There are potential causal associations between childhood obesity and T2DM as well as CHD, with a bidirectional causal relationship between T2DM and CHD. T2DM also plays a mediating role in the association between childhood obesity and CHD.

Objective: To investigate the spatio-temporal clustering characteristics of influenza in Shaoxing City, Zhejiang Province from 2015 to 2024, so as to provide the basis for formulating influenza prevention and control strategies. Methods: Influenza case data in Shaoxing City from 2015 to 2024 were collected through the Infectious Disease Surveillance Reporting System of the Chinese Disease Prevention and Control Information System. Descriptive epidemiological methods analyses were used to analyze the epidemiological characteristics of influenza. Spatial autocorrelation and spatio-temporal scanning were used to analyze the spatio-temporal clustering characteristics of influenza. Results: A total of 328 759 influenza cases were reported in Shaoxing City from 2015 to 2024, with an average annual reported incidence of 639.90/100 000, which showed an upward trend (AAPC=68.95%, P<0.05). The peak incidence period was from December to February of the following year, with 193 051 cases reported, accounting for 58.72%. There were 165 408 male cases and 163 351 female cases, with a male-to-female ratio of 1.01∶1. Children and adolescents aged 0-<15 years constituted the high-incidence population, while students represented the predominant occupational category, comprising 113 589 cases (34.55%). Keqiao District, Shengzhou City, and Yuecheng District had the top three average annual reported incidence of influenza, at 995.64/100 000, 734.66/100 000, and 687.44/100 000, respectively. Spatial autocorrelation analysis showed that, there were 155 high-high aggregation areas in Shaoxing City from 2015 to 2024, which gradually expanded from the local aggregation in the central part of Shengzhou City to Keqiao District and then spread to Yuecheng District. Spatio-temporal scanning analysis showed that, from November 2023 to February 2024, the strongest spatio-temporal clustering of influenza centered on Keqiao Street in Keqiao District, covering 11 towns (streets) in Yuecheng District and Keqiao District. From 2015 to 2018, the primary-type clustering of influenza was mainly concentrated in Xinchang County and Shengzhou City. After 2019, they gradually shifted to Yuecheng District and Keqiao District, with the main clustering period being from November to February of the following year. Conclusions The incidence of influenza in Shaoxing City from 2015 to 2024 showed an upward trend, with obvious spatio-temporal clustering. The clustering area expanded from Shengzhou City in the central region to Keqiao District and Yuecheng District in the northern region, mainly clustering from November to February of the following year.

Colorectal cancer (CRC) is one of the leading causes of cancer-related morbidity and mortality worldwide, highlighting the urgent need for novel preventive and therapeutic strategies. Emerging research highlights the crucial role of the gut microbiota, including bacteria, fungi, viruses, and their metabolites, in the pathogenesis of CRC. Dysbiosis, characterized by an imbalance in microbial composition, contributes to tumorigenesis through immune modulation, metabolic reprogramming, and genotoxicity. Specific bacterial species, such as Fusobacterium nucleatum and enterotoxigenic Bacteroides fragilis , along with fungal agents like Candida species, have been implicated in CRC progression. Moreover, viral factors, including Epstein-Barr virus and human cytomegalovirus, are increasingly recognized for their roles in promoting inflammation and immune evasion. This review synthesizes the latest evidence on host-microbiome interactions in CRC, emphasizing microbial metabolites, such as short-chain fatty acids and bile acids, which may act as both risk factors and therapeutic agents. We further discuss the latest advances in microbiota-targeted clinical applications, including biomarker-assisted diagnosis, next-generation probiotics, and microbiome-based interventions. A deeper understanding of the role of gut microbiome in CRC pathogenesis could pave the way for diagnostic, preventive, and personalized therapeutic strategies.
Humans ; Dysbiosis/microbiology* ; Colorectal Neoplasms/metabolism* ; Gastrointestinal Microbiome/physiology* ; Animals

Food-derived bioactive peptides (FBPs), particularly those with ten or fewer amino acid residues and a molecular weight below 1300 Da, have gained increasing attention for their safe, diverse structures and specific biological activities. The development of FBP-based functional foods and potential medications depends on understanding their structure‒activity relationships (SARs), stability, and bioavailability properties. In this review, we provide an in-depth overview of the roles of FBPs in treating various diseases, including Alzheimer's disease, hypertension, type 2 diabetes mellitus, liver diseases, and inflammatory bowel diseases, based on the literature from July 2017 to Mar. 2023. Subsequently, attention is directed toward elucidating the associations between the bioactivities and structural characteristics (e.g., molecular weight and the presence of specific amino acids within sequences and compositions) of FBPs. We also discuss in silico approaches for FBP screening and their limitations. Finally, we summarize recent advancements in formulation techniques to improve the bioavailability of FBPs in the food industry, thereby contributing to healthcare applications.
Humans ; Peptides/therapeutic use* ; Structure-Activity Relationship ; Functional Food ; Diabetes Mellitus, Type 2/drug therapy* ; Biological Availability ; Alzheimer Disease/drug therapy* ; Inflammatory Bowel Diseases/drug therapy* ; Hypertension/drug therapy* ; Liver Diseases/drug therapy* ; Bioactive Peptides, Dietary

Objective:To explore the effectiveness of streamlined modular teaching based on the organ system in standardized residency training in emergency medicine.Methods:We enrolled residents on standardized training in the Second Clinical College of Tongji Medical College of Huazhong University of Science and Technology from July 2020 to July 2021. They were randomly divided in a 1∶1 ratio into conventional group (25 trainees, adopting a traditional standardized teaching method) and modular group (25 trainees, adopting streamlined modular teaching based on the organ system in addition to the method of the conventional group). At the end of training, all the trainees were assessed for academic performance and teaching-related indicators through an exam and questionnaire survey, and the teachers were surveyed for the degree of satisfaction with the teaching method. Data were analyzed by the t-test and chi-squared test using SPSS 21.0 software. Results:The modular group had a significantly higher total final exam score than the conventional group [(93.52±0.49) vs. (84.44±0.57), t=12.02, P<0.001]. Specifically, the modular group had significantly higher scores than the conventional group in emergency medicine theory, medical history taking and writing, physical examination and procedures, interpretation of examination results, and treatment and management ( t=3.62, 4.29, 4.22, 10.09, 7.56, all P<0.001). The modular group was also superior to the conventional group in terms of teaching-related indicators (all P<0.05). All participating teachers were satisfied with the new teaching method. Conclusions:The streamlined modular teaching method based on the organ system is beneficial for the standardized training of residents in emergency medicine, which is worthy of promotion.

Hypoxia-inducible factor (HIF-1α), a core transcription factor responding to changes in cellular oxygen levels, is closely associated with a wide range of physiological and pathological conditions. However, its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely elusive. Here, we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-1α-deficient human vascular cells including vascular endothelial cells, vascular smooth muscle cells, and mesenchymal stem cells (MSCs), as a platform for discovering cell type-specific hypoxia-induced response mechanisms. Through comparative molecular profiling across cell types under normoxic and hypoxic conditions, we provide insight into the indispensable role of HIF-1α in the promotion of ischemic vascular regeneration. We found human MSCs to be the vascular cell type most susceptible to HIF-1α deficiency, and that transcriptional inactivation of ANKZF1, an effector of HIF-1α, impaired pro-angiogenic processes. Altogether, our findings deepen the understanding of HIF-1α in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.
Humans ; Vascular Endothelial Growth Factor A/metabolism* ; Endothelial Cells/metabolism* ; Transcription Factors/metabolism* ; Gene Expression Regulation ; Hypoxia/metabolism* ; Cell Hypoxia/physiology*

OBJECTIVE To study the effect of fluoropezil on embryo-fetal developmental toxicity and toxicokinetics in rabbits,and provide reference for clinical medication.METHODS According to the sequence of pregnancy,pregnant rabbits were divided into five groups:vehicle control group(1%hydroxy-propyl methylcellulose+1.5%polyethylene glycol 400 aqueous solution),positive control group(cyclo-phosphamide 18 mg·kg-1),and fluoropezil(3.6,9.0 and 22.5 mg·kg-1)groups.The vehicle control group and the fluoropezil groups were ig administrated on the 6th to 18th day of gestation(GD6-18)while the positive control group was ig given cyclophosphamide on GD6-20.The pregnant rabbits were sacri-ficed on GD28,and the embryo-fetal development was detected.Sex hormone levels of pregnant rabbits on GD5,GD18 and GD28 were detected by ELISA method.Blood samples with toxokinetics were collected for concomitant toxic generation at the first and last administration,and drug concentrations in fetal,placenta and amniotic fluid were detected with liquid chromatography tandem mass spectrometry(LC-MS/MS).RESULTS Fluoropezil 3.6,9.0 and 22.5 mg·kg-1 had no significant effect on body mass,mass gain,food consumption,pregnancy outcomes,fetal appearance,viscera,skeletal and physical growth and development of pregnant rabbits.Only on GD18 or GD28,the levels of follicle stimulating hormone,estra-diol and progesterone in each dose group fluctuated to some extent.The combined toxokinetics results indicated that fluoropezil could cross the placental barrier of the rabbits,but did not accumulate in preg-nant rabbits or fetuses.Fetal mass,crown-rump length and uterus mass in the cyclophosphamide group were lower than those in the vehicle control group.The appearance and bone of the cyclophos-phamide group were positive.CONCLUSION The no observed adverse effect level(NOAEL)of fluoro-pezil toxicity on rabbit embryo-fetal development is 22.5 mg·kg-1,which is 125 times of the effective dose.At the dosage level of 22.5 mg·kg-1,Cmax is 1093 μg·L-1,and AUC(0-24 h)6650 μg·h·L-1 on GD18.

OBJECTIVE To investigate the mechanisms by which Pinggan Yishen Decoction(PGYSD)contributes to alleviating target organ damage in spontaneously hypertensive rats.METHODS The chemical components of PGYSD were determined by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)and were analyzed by target a-nalysis and functional enrichment combined with network pharmacology methods to predict the potential mechanism of PGYSD in trea-ting hypertension and its target organ damage.Spontaneously hypertensive rats were randomly divided into the model group,low-dose PGYSD group(2 g·kg-1),high-dose PGYSD group(5 g·kg-1),and valsartan group(7.2 mg·kg-1),with 6 rats in each group.Wistar-Kyoto rats were used as the control group,and the control group and the model group were gavaged with normal saline for 8 consecutive weeks.HE and Masson staining were used to observe the pathological damage and fibrosis degree of rat heart and tho-racic aorta.Immunohistochemical staining and Western blot were used to detect the expression level of EGFR in the heart,liver and kidney of rats.Immunofluorescence staining was used to detect the co-localization of EGFR and EEA1 in the heart,liver and kidney of rats.RESULTS Twenty-six components of PGYSD were detected by UPLC-Q-TOF/MS.Network pharmacology revealed that EG-FR,PIK3R1 and EP300 may be key therapeutic targets of action of PGYSD for the treatment of hypertension and its target organ dam-age,and that the treatment of hypertension and its target organ damage by PGYSD may be closely related to EGFR tyrosine kinase in-hibitor resistance,lipids and atherosclerosis and HIF-1 signaling pathway.The high-dose group of PGYSD significantly reduced sys-tolic blood pressure and mean blood pressure in rats(P<0.05,P<0.01),attenuated pathological damage and fibrosis in the heart and thoracic aorta(P<0.01,P<0.001),significantly reduced the expression level of EGFR in the liver and kidney of rats(P<0.01),and treated fibrosis in liver and kidney,reduced the co-localization of EGFR and EEA1 in the kidney of rats(P<0.001),attenuated fibro-sis in kidney.CONCLUSION The paper integrates UPLC-Q-TOF/MS,network pharmacology and spontaneously hypertensive rat model and preliminarily explores the effect mechanism of PGYSD in the treatment of hypertension and its target organ damage,provi-ding a scientific basis for further mechanism research and clinical application of PGYSD in the treatment of hypertension.

Objective To investigate the effects and mechanisms of Zhenxin Anshen Prescription(composed of Os Draconis,Ostreae Concha,Lophatheri Herba,Drynariae Rhizoma,Poria)on mice with atopic dermatitis(AD)based on the calcium channel regulator 1(ORAI1)/nuclear factor of T-cells(NFAT)signalling axis.Methods Thirty-six BALB/c mice were randomly divided into a blank control group,a model group,a Cetirizine group(1.3 mg·kg-1)and a Zhenxin Anshen Prescription group(36.36 g·kg-1),with nine mice in each group.AD mouse model was established using 1-chloro-2,4-dinitrobenzene(DNCB)induction.The drug was administered by gavage once a day for 2 weeks.At the end of drug administration,the area of skin lesions was measured and the severity of skin lesions was scored;spleen mass was measured and spleen index was calculated;pathological changes of skin lesion tissues were observed by HE staining;interleukin 4(IL-4),IL-13 and thymic stromal lymphopoietin(TSLP)in serum were detected by ELISA;and the protein expression levels of ORAI1,calmodulin phosphatase A(CaN)and nuclear factor of T cells 2(NFAT2)were detected by Western Blot.Results Compared with the blank control group,the skin lesion score of mice in the model group was significantly increased(P＜0.01),the skin lesion area was significantly enlarged(P＜0.01);the thickness of the epidermis and dermis were significantly increased(P＜0.01),hyperkeratosis of the epidermis,hypertrophy of the stratum spinosum,and infiltration of inflammatory cells such as eosinophils and lymphocytes can be seen in the dermis;the splenic index and serum IL-4,IL-13,TSLP levels were significantly increased(P＜0.01);protein expression levels of CaN,NFAT2,ORAI1 were significantly increased in the skin lesion tissues(P＜0.01).Compared with the model group,the dermatitis score of mice in the Zhenxin Anshen Prescription group was significantly decreased(P＜0.01),the lesion area was significantly reduced(P＜0.01),the epidermal and dermal thicknesses(P＜0.01),the hyperkeratosis of epidermis was alleviated,the spinous layer was slightly hypertrophic,and there was a small amount of inflammatory cell infiltration in the dermis;the splenic index and the levels of serum IL-4,IL-13,and TSLP were significantly decreased(P＜0.01);the protein expressions levels of CaN,NFAT2,and ORAI1 in the skin lesion tissues were significantly decreased(P＜0.01).Conclusion Zhenxin Anshen Prescription can ameliorate dermatopathological injury in DNCB-induced AD mice,and the mechanism may be related to its ability to inhibit the protein expressions of ORAI1,CaN and NFAT2,reduce the levels of serum type 2 inflammatory factors TSLP,IL-4 and IL-13,and ameliorate cutaneous inflammation and itching through immunomodulation.