ObjectiveTo develop a standardized classification model for traditional Chinese medicine （TCM） syndrome patterns of mixed hemorrhoids using multi-center real-world data， and unveil their distribution patterns and core risk factors， thereby providing evidence-based support for standardizing TCM syndrome differentiation and implementing precision interventions. MethodsA multi-center cross-sectional study was conducted， enrolling 13 283 mixed hemorrhoid patients from eight hospitals in Jiangsu Province between September 1st， 2023 and December 31st， 2024. DeepSeek-R1-Distill-Qwen-7B and LLaMA-3.3 large language models （LLM） were integrated with latent class analysis （LCA） to perform unsupervised learning and latent class modeling of TCM symptomatology. Potential risk factors were screened via univariate analysis， followed by logistic regression to identify independent risk factors for each syndrome pattern. ResultsThe model's performance indicators were stable and reliable across different clinical data types，i.e. in the outpatient records， past medical history （F1=99.7%）， current medical history （F1=94.9%）， and specialist examination （F1=90.7%）； in inpatient records， past medical history （F1=98.2%）， current medical history （F1=91.2%）， specialist examination （F1=90.3%）， and discharge status （F1=90.6%）. Latent class mode-ling identified four core TCM syndrome patterns including spleen deficiency and qi sinking syndrome （915 cases， 6.89%）， damp-heat pouring downward syndrome （10 820 cases， 81.46%）， qi stagnation and blood stasis syndrome （1252 cases， 9.43%）， and wind injuring intestinal collaterals syndrome （296 cases， 2.22%）， with respective latent class probabilities of 0.069， 0.815， 0.094， and 0.022. Logistic regression demonstrated that gender， age， disease duration， hypertension， diabetes， hyperlipidemia， constipation， smoking history， and alcohol consumption were independent risk factors for pattern differentiation （P＜0.05）. The efficacy validation evaluation revealed that the cure rates for patients with spleen deficiency and qi sinking syndrome and qi stagnation and blood stasis syndrome were higher than those for patients with damp-heat pouring downward syndrome （adjusted P＜0.05）， with no statistically significant differences among other syndrome patterns. ConclusionDamp-heat pouring downward syndrome is the predominant syndrome in mixed hemorrhoids. Gender， age， disease duration， hypertension， diabetes， hyperlipi-demia， constipation， smoking history， and alcohol consumption are independent risk factors for the differentiation of syndrome types.

Fucoxanthin is a pigment found in plants and animals such as algae， marine plankton and aquatic shellfish， and holds significant potential for development in the pharmaceutical field. This review introduces the anti-inflammatory， antioxidant， anticancer， anti-obesity， and other pharmacological effects of fucoxanthin， as well as recent advances in drug design research. It was found that fucoxanthin can exert anti-inflammatory and antioxidant effects through mechanisms such as activating AMP- activated protein kinase related signaling pathways， regulating the expression of inflammatory factors， altering microbial stability， thereby improving conditions such as metabolic associated fatty liver disease and colitis. It can exert selective antitumor effects through multi-target synergistic actions； and it was also found that it can exert anti-obesity effects by regulating the intestinal microbiota. Its characteristic functional groups （such as hydroxyl and epoxy groups） possess target specificity and reversible inhibitory properties， making it a suitable template for guiding the design and development of novel drugs， thereby providing new insights for breaking through the limitations of traditional drug design.

COMPERA 2.0 risk stratification has been demonstrated to be useful in patients with precapillary pulmonary hypertension (PH). However, its suitability for patients at risk for post-capillary PH or PH associated with left heart disease (PH-LHD) is unclear. To investigate the use of COMPERA 2.0 in patients with severe aortic stenosis (SAS) undergoing transcatheter aortic valve replacement (TAVR), who are at risk for post-capillary PH, a total of 327 eligible SAS patients undergoing TAVR at our institution between September 2015 and November 2020 were included in the study. Patients were classified into four strata before and after TAVR using the COMPERA 2.0 risk score. The primary endpoint was all-cause mortality. Survival analysis was performed using Kaplan-Meier curves, log-rank test, and Cox proportional hazards regression model. The study cohort had a median (interquartile range) age of 76 (70‒80) years and a pulmonary arterial systolic pressure of 33 (27‒43) mmHg (1 mmHg=0.133 kPa) before TAVR. The overall mortality was 11.9% during 26 (15‒47) months of follow-up. Before TAVR, cumulative mortality was higher with an increase in the risk stratum level (log-rank, both P<0.001); each increase in the risk stratum level resulted in an increased risk of death (hazard ratio (HR) 2.53, 95% confidential interval (CI) 1.54‒4.18, P<0.001), which was independent of age, sex, estimated glomerular filtration rate (eGFR), hemoglobin, albumin, and valve type (HR 1.76, 95% CI 1.01‒3.07, P=0.047). Similar results were observed at 30 d after TAVR. COMPERA 2.0 can serve as a useful tool for risk stratification in patients with SAS undergoing TAVR, indicating its potential application in the management of PH-LHD. Further validation is needed in patients with confirmed post-capillary PH by right heart catheterization.
Humans ; Aortic Valve Stenosis/complications* ; Aged ; Hypertension, Pulmonary/mortality* ; Male ; Female ; Transcatheter Aortic Valve Replacement ; Aged, 80 and over ; Risk Assessment/methods* ; Proportional Hazards Models ; Kaplan-Meier Estimate ; Retrospective Studies

Objective To investigate the killing effect of the recombinant oncolytic influenza virus OvFlu-GM-CSF,constructed using reverse genetics(RG)technology,in combination with chemotherapy drug,gemcitabine(GEM),against pancreatic cancer cells.Methods The recombinant oncolytic virus OvFlu-GM-CSF was successfully rescued using RG technology in our previous study.The virus was then comprehensively characterized through chicken red blood cell hemagglutination assay,transmission electron microscopy,and viral replication assay.CCK-8 assay was utilized to determine the impact of OvFlu-GM-CSF viruses[multiplicities of infection(MOI):0,0.1,1.0,3.0]on the survival rate of pancreatic cancer cell lines(Panc02,PANC-1,SW1990,BxPC-3)and normal pancreatic ductal epithelial cells(HPDE6-C7)after treatment for 24,48 or 72 h.Using a subcutaneous tumor-bearing mouse model of pancreatic cancer,36 female C57BL/6 mice(6 weeks old)were randomly divided into PBS group,recombinant oncolytic virus group,GEM group,and the combined treatment group,with 9 mice in each group.PBS(100 μL/animal)or OvFlu-GM-CSF virus(1× 107PFU/100 μL)was given to the mice of the corresponding groups through intratumoral injection,while GEM(100 mg/kg)was injected intraperitoneally,once per 3 days,for totally 9 times.Changes in tumor volume and survival rate were monitored.Multi-immunofluorescence staining was employed to analyze T cell infiltration and proliferation in the tumor tissues.HE staining was performed to observe the pathological changes in major organs(heart,liver,lungs,kidneys and brain),and the serum levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)were measured to evaluate the safety of the recombinant oncolytic virus.Results The recombinant oncolytic influenza virus OvFlu-GM-CSF has a hemagglutination titer of 28,typical morphological features of influenza virus,and can selectively replicate within pancreatic cancer cells.At the cellular level,the viruses demonstrated a significant selective cytotoxic effect on Panc02,PANC-1,SW1990,and BxPC-3 cells under the conditions of 48 h post-infection and MOI=3.0,when compared to 48 h post-infection and MOI=0(P＜0.01).The cell survival rate was gradually decreased with the increase in MOI value and the extension of infection time(P＜0.01),but the viruses showed no significant effect on normal pancreatic ductal epithelial cells(HPDE6-C7).In the pancreatic cancer tumor-bearing mouse model,the combined treatment of the viruses+GEM significantly reduced the tumor volume than simple virus treatment and simple GEM treatment(P＜0.01),and enhanced the infiltration of T cells in the tumor tissues.No obvious pathological changes were observed in the above-mentioned major organs.Additionally,there were no significant differences in the serum levels of ALT and AST in the OvFlu-GM-CSF group,GEM group,and OvFlu-GM-CSF+GEM group compared to the PBS group.Conclusion RS technology-constructed recombinant oncolytic influenza virus OvFlu-GM-CSF,when combined with the chemotherapeutic agent GEM,enhances the cytotoxic efficacy against pancreatic cancer cells and effectively activates the host's anti-tumor immune response.

Guanylate binding protein subunit β-2(GNB2)is an important part of G protein family.In the process of cell signal transduction,GNB2 plays a structural support and regulatory role in G protein complex,ensuring the correct transmission and amplification of signals,interacting with receptors and regulating vari-ous effector enzymes and ion channels,and mediating a variety of physiological functions.Therefore,GNB2 plays a key role in cell signaling,and participates in the regulation of cell proliferation,differentiation and mi-gration and other biological processes.This article reviews the research progress of GNB2,focusing on its structure,function,regulatory mechanism,disease correlation and importance in tumor research.

Objective: To explore the prevalence of elevated blood pressure and overweight/obesity and their comorbidities among Tibetan middle school students in Lhasa, and to analyze their association with lifestyle and other factors, so as to provide a basis for the intervention measures targeting elevated blood pressure, overweight and obesity among middle school students in high altitude area. Methods: Using a stratified cluster random sampling method in September 2021, a total of 1 488 Tibetan junior and high students from Lhasa City were investigated with blood pressure measurement, physical examination and questionnaire survey. The influencing factors of elevated blood pressure, overweight and obesity and their comorbidities association were analyzed by multivariate Logistic regression. Results: The prevalence of elevated blood pressure, overweight/obesity and their comorbidities were 17.8%, 17.4% , 5.0% respectively. Multivariate Logistic regression analysis showed that age( OR =0.81), residence, body mass inex(BMI) and gender were the influencing factors of elevated blood pressure; and the risks of elevated blood pressure in female students were higher than male students ( OR =1.89), suburban students were higher than urban students ( OR =8.06), overweight and obesity groups were higher than normal groups ( OR =2.55, 2.87) ( P <0.05). Adjusting for confounding factors such as gender, residence and school, and BMI (only for elevated blood pressure), daily screen time ≥2 h was positively correlated with elevated blood pressure, overweight/obesity and its comorbidities ( OR =1.56, 1.59 , 2.51) ( P <0.05). Conclusions The prevalence of elevated blood pressure, overweight/obesity are relatively high in Lhasa. Longer screen time is a common factor affecting with elevated blood pressure, overweight/obesity and comorbidities among Tibetan students. Measures should be taken intervene in the lifestyle of Tibetan students, in order to reduce elevated blood pressure and overweight/obesity.

Background In the Global Burden of Disease research, it has been found that atmospheric fine particulate matter (PM_2.5) pollution significantly harms human health. Currently, there is limited research on polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) that exhibit high toxicity effects in PM_2.5 . Objective By studying the spatiotemporal distribution and variation characteristics of PCDD/Fs in PM_2.5 in Pudong area of Shanghai, to assess the associated population health risk. Methods This study set up 28 sampling points in Pudong area. One sample of PM_2.5 was collected during winter (February 2022) and summer (July 2022) at each site, with a sampling period lasting 24 h. The concentration of PM_2.5 was measured by membrane filter method, and the content of 17 kinds of 2,3,7,8-substituted chlorinated PCDD/Fs in the samples was analyzed using isotope dilution. Seasonal variations (winter and summer) in the concentrations of PM_2.5 and PCDD/Fs were evaluated, sources of PCDD/Fs pollution were tracing by principal component analysis, and health risks to the population from respiratory exposure to PCDD/Fs were estimated by VLIER-HUMAAN model. Results The PM_2.5 concentrations in the 28 samples ranged from 10 to 126 μg·m⁻³, while the concentrations of PCDD/Fs in PM_2.5 ranged from 58 to 2625 fg·m⁻³. The concentration of PM_2.5 during winter (11-126 μg·m⁻³) was higher than that during summer (10-60 μg·m⁻³). The concentration range of PCDD/Fs in winter was from 58 to 2625 fg·m⁻³, which corresponded to a range of toxic equivalent quantity (WHO-TEQ) concentration from 2.99 to 40.97 fg·m⁻³ when taking World Health Organization's toxic equivalency factor (WHO-TEQ); the concentration range of PCDD/Fs in summer was from 72 to 446 fg·m⁻³, which corresponded to a range of WHO-TEQ concentration from 2.66 to 16.61 fg·m⁻³. This range in summer was significantly lower than that observed in winter. The results of principal component analysis revealed that waste incineration was the primary source of PCDD/Fs in winter PM_2.5 in the area, whereas traffic emissions emerged as the main source in summer. The assessment of Pudong residents' respiratory exposure to PCDD/Fs in PM_2.5 showed significantly higher exposure of children in summer and winter than that of adults, indicating higher susceptibility of children to air pollutants. Both the hazard ratios (HR) for children and adults were below 1, while the cancer risks (CR) ranged from 8.41×10⁻⁸ to 2.35×10⁻⁶. Notably, during winter, the CR at 4 locations slightly exceeds 1×10⁻⁶, indicating a potential carcinogenic risk. Conclusion The overall pollution level of PCDD/Fs in PM_2.5 in Pudong area is relatively low, but it shows clear seasonal patterns. Waste incineration and traffic are the main sources of PCDD/Fs in PM_2.5 in the area. Although the cancer risk of exposure to PCDD/Fs in PM_2.5 for children or adults is relatively low, there is a certain risk at some locations in winter, necessitating additional monitoring and control.

Objective:To construct a comprehensive material management system for public hospitals to meet the needs of material homogeneity and refined management under the hospital's multi-campus development model.Methods:By systematically sorting out the process and each link of the whole life cycle of hospital material management,using Java programming language,browser and server(B/S)architecture,setting up the integrated management platform module of medical equipment,the process module of each link of the material management system and the authority management module,the comprehensive material management system of public hospitals was constructed.The information call,mutual connection and restriction mechanism between the component modules were determined,and the dynamic real-time usage data and status of hospital materials were uniformly supervised.The homogeneity and fine management effects of hospital materials in Beijing Children's Hospital Capital Medical University before and after the application of the system were compared.Results:The integrated material management system of public hospitals realized full lifecycle coverage of hospital materials,the collaboration between various business modules and the smooth operation of the system,and realized the coordination of basic information,business and resources of hospital materials,as well as the homogeneity,refinement and integrated management of cross-campus materials.After the application of the system,seamless real-time data docking between different hospital campuses was realized,the average time of receiving materials in clinical departments was shortened by 2 hours compared with that before the application of the system,the review efficiency of material warehousing data,consumption data and inventory data was increased by 30%,and the backtracking error rate of the whole process of materials was reduced to 0.2%.Conclusion:The comprehensive material management system of public hospitals can improve the efficiency of material management in the operation of multiple hospital campuses,reduce management costs,and realize the homogeneity,refinement and scientificization of hospital material management.

The efficient clinical treatment of oral squamous cell carcinoma(OSCC)is still a challenge that demands the development of effective new drugs.Phenformin has been shown to produce more potent anti-tumor activities than metformin on different tumors,however,not much is known about the influence of phenformin on OSCC cells.We found that phenformin suppresses OSCC cell proliferation,and promotes OSCC cell autophagy and apoptosis to significantly inhibit OSCC cell growth both in vivo and in vitro.RNA-seq analysis revealed that autophagy pathways were the main targets of phenformin and identified two new targets DDIT4(DNA damage inducible transcript 4)and NIBAN1(niban apoptosis regulator 1).We found that phenformin significantly induces the expression of both DDIT4 and NIBAN1 to promote OSCC autophagy.Further,the enhanced expression of DDIT4 and NIBAN1 elicited by phenformin was not blocked by the knockdown of AMPK but was suppressed by the knockdown of transcription factor ATF4(activation transcription factor 4),which was induced by phenformin treatment in OSCC cells.Mechanistically,these results revealed that phenformin triggers endoplasmic reticulum(ER)stress to activate PERK(protein kinase R-like ER kinase),which phosphorylates the transitional initial factor eIF2,and the increased phosphorylation of eIF2 leads to the increased translation of ATF4.In summary,we discovered that phenformin induces its new targets DDIT4 and especially NIBAN1 to promote autophagic and apoptotic cell death to suppress OSCC cell growth.Our study supports the potential clinical utility of phenformin for OSCC treatment in the future.

Objective:To investigate the application of Wuxing music combined with traditional Chinese medicine bath and golden paste encapsulation in patients with psoriasis vulgaris(blood-heat syndrome).Methods:In this prospective study,80 patients with psoriasis vulgaris(blood heat syndrome)admitted to our hospital from Nov 2020 to Nov 2022 were included and randomly divided into the control group and the observation group,with 40 cases in each group.The control group received routine nursing intervention,and the observation group received Wuxing music combined with traditional Chinese medicine bath and golden paste encapsulation nursing on the basis of control group,4 weeks as a course of treatment.After 2 courses of nursing,nursing effect,the scores of SCL-90 and DQOLS,the levels of serum inflammatory factors[interleukin-13(IL-13),transforming growth factor-β(TGF-β),and tumor necrosis factor-α(TNF-α)],and nursing satisfaction were compared between the two groups.Results:The area and severity of skin lesions in the two groups were lower than before nursing,and the changes in the observation group were more significant(P＜0.05).The scores of SCL-90 and DQOLS in the two groups were lower than those before nursing,and the changes in the observation group were more significant(P＜0.05).The levels of IL-13,TGF-β and TNF-α in the two groups were lower than those before nursing,and the levels of these indicators in the observation group were significantly lower than those in the control group(P＜0.05).The satisfaction rate of the observation group was higher than that of the control group(P＜0.05).Conclusions:Wuxing music combined with traditional Chinese medicine bath and golden paste encapsulation has a significant nursing effect on patients with psoriasis vulgaris(blood heat syndrome).It can decrease serum inflammatory factors,alleviate the degree of skin lesions,and iprove quality of life and nursing satisfaction.