Vitiligo is a chronic and refractory pigmentary loss skin disease with a complex pathogenesis. Traditional Chinese medicine（TCM） offers advantages in treating vitiligo， such as multi-component and multi-target effects， delivering definite clinical efficacy. This article summarizes the action mechanisms of TCM monomer components and compound formulations in the treatment of vitiligo. It is found that pinostrobin， tribuloside and Erzhi pills can activate the cyclic adenosine monophosphate/protein kinase A （cAMP/PKA） signaling pathway； cannabidiol and tanshinone Ⅱ A can activate the p38 mitogen-activated protein kinase（p38 MAPK）signaling pathway； Ginkgo biloba extract EGb761 and astragaloside Ⅳ can activate the aryl hydrocarbon receptor（AhR） signaling pathway； escin and psoralen derivative BSP-1 can activate the Wnt/β-catenin signaling pathway； apigenin and Baiban granules can activate the nuclear factor erythroid 2-related factor 2/heme oxygenase-1（Nrf2/HO-1） signaling pathway； hyperoside and kaempferol can activate the phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt） signaling pathway； Ruyi heibai powder can activate the programmed death-1/programmed death-ligand 1（PD-1/PD-L1） signaling pathway； Compound honghua buji granules and demethylzeylasteral can inhibit the Janus kinase/signal transducer and activator of transcription （JAK/STAT） signaling pathway. These mechanisms promote melanin production and deposition， reduce oxidative stress， inhibit the destruction of melanocytes by autoimmunity， and reduce melanocyte apoptosis， thereby exerting therapeutic effects on vitiligo.

Objective To investigate the diagnostic value of our regression model based on quantitative parameters of dual-energy CT and clinical features for stages T2 and T3 colorectal cancer.Methods A cross-section study was performed on 91 patients with colorectal cancer confirmed by postoperative pathology in our hospital from January 2022 to November 2023.All of them underwent dual-energy CT examination.According to the pathological T staging criteria of Chinese Colorectal Cancer Diagnosis and Treatment Standard(2020 Edition),they were divided into T2 group(n=43)and T3 group(n=48).Univariate analysis was used to compare the differences in quantitative CT parameters and clinical features between the 2 groups,and the obtained significant variables were employed to construct diagnosis models by univariate or multivariate logistic regression analysis.The area under receiver operating characteristic curve(AUC)of the CT parametric model and the model combined with clinical features was compared to evaluate the efficacy of diagnosing T2 and T3 stages.Results Univariate analysis showed that carcinoembryonic antigen(CEA),N stage,tumor location,tumor longest diameter(LD),CT value of virtual noncontrast(CT-VNC),fat fraction,electron density(Rho)and dual energy index(DEI)were significantly different between the T2 and T3 groups(P＜0.05).Multivariate logistic regression analysis found that N stage,tumor location,LD,fat fraction and DEI were independent risk factors for the diagnosis of stage T3.The AUC value of the model of above CT parameters in diagnosing stage T3 colorectal cancer was 0.671(95％CI:0.558～0.783),and the AUC value of the combined model of above CT parameters and clinical features was 0.886(95％CI:0.815～0.957),and statistical difference was observed in the AUC value between the combined model and the CT parametric model(P＜0.01).Conclusion The regression model constructed with dual-energy CT quantitative parameters combined with clinical features has high value in the preoperative diagnosis of stages T2 and T3 colorectal cancer before surgery.

Objective To explore the effects of hypoxia on spermatid differentiation and stability of sperm flagellar microtubule,and investigate the underlying molecular mechanisms in order to clarify the potential adverse effects of hypoxia on male reproductive function.Methods Forty-eight 8-week-old healthy male SD rats(weighing 300～399 g)were subjected in this study.The experiments included ① an oxygen concentration gradient experiment(n=6):21％oxygen was regarded as normoxia(control),and 13.5％,11.8％,and 10.4％ oxygen were used to simulate hypoxic environments at altitudes of 3 500,4 500 and 5 500 m,respectively,for a continuous exposure of 2 months;② a time gradient experiment(n=6):the rats were exposed to 10.4％ oxygen for 0,0.5,1,and 2 months,respectively.Flow cytometry was employed to isolate round spermatids,and the following methods were employed to measure relevant indicators:① RNA sequencing to analyze gene expression profile changes related to impaired spermatogenesis and abnormal flagellar structure under hypoxic stress;②Western blotting to detect the expression levels of key proteins CEP290,RING 1A,and H2AK119ub;③ fluorescence recovery after photobleaching(FRAP)to monitor microtubule assembly dynamics and assess the immediate impact of hypoxia on microtubule stability.Results In the oxygen concentration gradient experiment,after 2 months of exposure to 10.4％ oxygen,the proportions of spermatogonia,secondary spermatocytes,and round spermatids in rat seminiferous tubules were significantly increased(P＜0.05),reaching 1.33±0.04,1.06±0.01 and 1.60±0.02 times higher,respectively than that of the 21％ normoxia group.Conversely,the proportions of primary spermatocytes and elongated spermatids were obviously decreased(P＜0.05),taking 0.89±0.01 and 0.88±0.000 2 times respectively when compared with that of the 21％ normoxia group,in a oxygen concentration-depended manner.In the time gradient experiment,after 0.5 months of exposure to 10.4％oxygen,the proportions of spermatogonia,secondary spermatocytes,and round spermatids began to increase(P＜0.05),reaching 1.11±0.03,1.04±0.01 and 1.29±0.003 times higher,respectively than that of the 0-month control group.The proportions of primary spermatocytes and elongated spermatids started to significantly decrease(P＜0.05)after 1 month of exposure,only 0.94±0.03 and 0.95±0.008 times,respectively than that of the 0-month control group.After 2 months of exposure to 10.4％ oxygen,the rate of sperm tail abnormalities in the epididymis of rats was significantly increased(P＜0.05),rising from(12.1±1.7)％ in the 21％ normoxia group to(30.8±3.7)％.In G2 spermatocytes exposed to 1％ hypoxia for 24 h,FRAP revealed a decrease in microtubule assembly rate and enhanced microtubule dynamic instability,with the maximum fluorescence recovery value decreasing from 0.37±0.02 in the normoxia group to 0.29±0.01.The results of RNA sequencing showed that under hypoxic condition,the transcription level of the key cilium basal body molecule CEP290 was increased,with an upregulation of 1.81±0.11 times than that of the 21％ normoxia group.In contrast,the expression levels of PRC1 complex members RING 1A,RING 1B,CBX2,PHC1,and PCGF1 were decreased,to 0.74±0.02,0.73±0.01,0.78±0.02,0.71±0.01 and 0.86±0.03 times of that of the 21％ normoxia group,respectively.Western blotting indicated that the protein level of CEP290 was up-regulated in the hypoxia group,while that of RING 1A was down-regulated.ChIP-qPCR experiments showed that the binding of RING 1A and its product H2AK119ub to the CEP290 promoter were significantly decreased(P＜0.000 1),with binding strengths of 0.38±0.02 and 0.52±0.06 times of that of the 21％ normoxia group,respectively.In siRING 1A-treated G2 cells,the binding of H2AK119ub to the CEP290 promoter was significantly decreased(P＜0.000 1),with a binding strength of 0.74±0.06 times of that of the control group,while CEP290 mRNA level was significantly increased(P＜0.000 1),with an up-regulation of 3.35±0.37 times.Conclusion Hypoxic environment impair sperm flagellar microtubule stability via the RING 1A-H2AK119ub-CEP290 signaling axis,which affects spermatid differentiation and leads to spermatogenic dysfunction.

OBJECTIVES: To explore potential keywords, research clusters, collaborative pattern, and research trends in the field of medical technology management (MTM) through bibliometric analysis, providing insights for researchers, policy makers, and hospital administrators. METHODS: A retrieval formula was applied to the title, abstract, and keywords in the Web of Science (WoS) Core Collection, along with system-recommended terms, to identify articles on MTM. A total of 181 articles published between 1974 and 2022 were retained for quantitative analysis. The global trend of research output; total citations, average citations, and H-index; and bibliographic coupling, co-authorship, and keyword co-occurrence were analyzed using VOSviewer. RESULTS: The number of articles on MTM has been steadily increasing year by year. The focus of research has shifted from addressing basic medical needs to prioritizing emergency response and medical information security. The United States, Italy, and the United Kingdom emerged as the main contributors, with the United States leading in both volume of publications (60 articles) and academic impact (H-index = 21). Authors from the United Kingdom and the United States led the way in cross-border cooperation. The top five institutions, ranked by total link strength among cross-institutional authors, were primarily located in Canada and Spain. CONCLUSIONS The field of MTM has experienced stable growth over the past three decades (1993-2022). The shift of research focus has prompted a heightened emphasis on protecting patient privacy and ensuring the security of medical data. Future research should emphasize interdisciplinary and professional collaboration, as well as international cooperation and open sharing of knowledge.
Bibliometrics ; Humans ; Biomedical Technology

The translation of genetic findings from genome-wide association studies into actionable therapeutics persists as a critical challenge in Alzheimer's disease (AD) research. Here, we present PI4AD, a computational medicine framework that integrates multi-omics data, systems biology, and artificial neural networks for therapeutic discovery. This framework leverages multi-omic and network evidence to deliver three core functionalities: clinical target prioritisation; self-organising prioritisation map construction, distinguishing AD-specific targets from those linked to neuropsychiatric disorders; and pathway crosstalk-informed therapeutic discovery. PI4AD successfully recovers clinically validated targets like APP and ESR1, confirming its prioritisation efficacy. Its artificial neural network component identifies disease-specific molecular signatures, while pathway crosstalk analysis reveals critical nodal genes (e.g., HRAS and MAPK1), drug repurposing candidates, and clinically relevant network modules. By validating targets, elucidating disease-specific therapeutic potentials, and exploring crosstalk mechanisms, PI4AD bridges genetic insights with pathway-level biology, establishing a systems genetics foundation for rational therapeutic development. Importantly, its emphasis on Ras-centred pathways-implicated in synaptic dysfunction and neuroinflammation-provides a strategy to disrupt AD progression, complementing conventional amyloid/tau-focused paradigms, with the future potential to redefine treatment strategies in conjunction with mRNA therapeutics and thereby advance translational medicine in neurodegeneration.

With the rapid development of population aging in various countries around the world,the health and elderly care industry has been paid high attention.The standardization of smart health and elderly care technology and services is particularly important.This paper firstly reviewed the policies related to healthy elderly care in China.By analyzing the industrial standards and provincial standards issued,this paper focused on the policies proposed by the Shanghai Municipal Government for the standardization of smart health and elderly care,as well as the researches on the standard system and the construction of standard families.Shanghai group standards in the field of smart health and elderly care were summarized,including the guidelines for the construction of standard systems,elderly care service platforms,community elderly cafeterias,portable health monitoring terminals,indoor sports services,and home-based elderly care safety monitoring.A series of case analyses of the standardized implementation of the above aspects were also provided.Through standardization research and practice in recent years,it has been fully demonstrated that the standard research plays an important leading role in the field of smart health and elderly care.

Objective: To explore the relationship between beverage dependence and sleep quality among college students, providing empirical evidence for improving their sleep quality. Methods: From December 2024 to January 2025, a convenience sampling method was used to conduct a questionnaire survey among 3 974 college students from four universities in Anhui Province. The Beverage Addiction Scale for College Students (BASCS) was used to assess beverage dependence, and the Self rating Scale of Sleep(SRSS) was used to evaluate sleep quality. A multivariate Logistic regression model was employed to analyze the relationship between beverage dependence and sleep quality, and a restricted cubic spline model was used to examine the dose response relationship between the two. Results: The positive rate of beverage dependence symptoms among college students was 7.6%, with positive rates of 9.6%, 13.8%, and 7.4% for the withdrawal symptoms, health effects, and dependence symptoms dimensions, respectively. The detection rate of sleep disorders was 23.6%. Multivariate Logistic regression analysis showed that after adjusting for covariates such as grade, gender, and body mass index, compared with the no beverage dependence group, students with positive beverage dependence symptoms had a higher risk of sleep disorders( OR =3.71, 95% CI =2.87-4.80, P <0.01). The OR (95% CI ) for sleep disorders among students with positive symptoms in the withdrawal symptoms, health effects, and dependence symptoms dimensions were 2.80(2.22-3.53), 2.38(1.95-2.91), and 2.45(1.89-3.18)(all P <0.01). Further analysis using a restricted cubic spline model revealed that the overall beverage dependence score and its three dimensional scores were approximately linearly related to the risk of sleep disorders among college students (all nonlinear P >0.05). Conclusions Beverage dependence is associated with sleep quality among college students. Schools should take multiple approaches, such as health education on beverage awareness, to improve students sleep quality.

ObjectiveTo multidimensionally analyze the clinical effects of Qianyang Yuyin granules on elderly hypertensive patients through an "energy-inflammation-aging" network. MethodsRelevant datasets were retrieved from the GEO database. Gene set enrichment analysis （GSEA） was performed on the gene expression profiles of peripheral blood cells from patients with essential hypertension in dataset GSE24752. The GSEA referenced "GO gene sets" and "KEGG gene sets" to identify significantly enriched gene sets. A clinical trial was conducted using a randomized controlled study design. A total of 40 patients meeting the inclusion criteria were enrolled. The control group received standard antihypertensive treatment with angiotensin receptor blockers （ARBs） or combined calcium channel blockers （CCBs）. In contrast，the treatment group received Qianyang Yuyin Granules in addition to the standard treatment for 12 weeks. Blood pressure levels and clinical efficacy were observed，and changes in energy metabolism indicators，DNA damage markers，and senescence-associated secretory phenotype （SASP） in blood were measured using ELISA before and after treatment. ResultsGSEA results indicated significant energy metabolism dysregulation in hypertensive patients. Clinical findings showed that both groups achieved blood pressure control without significant intergroup differences. In terms of clinical efficacy，the treatment group had a significantly higher effective rate compared to the control group （95% vs 65%，P0.05）. After treatment，the treatment group showed a significant increase in NAD⁺ levels （P0.01），with higher levels compared to the control group （P0.05）. The treatment group also exhibited a greater reduction in DNA damage marker 8-OHdG （P0.01） and cell adhesion factors ICAM-1 and VCAM-1 （P0.01） compared to the control group. Pro-inflammatory cytokines IL-1β and IL-6 were significantly reduced in the treatment group （P0.01），with greater reductions compared to the control group （P0.05，P0.01）. Anti-inflammatory cytokines IFN-α，IL-4，and IL-10 were significantly elevated in the treatment group （P0.01），with higher levels compared to the control group （P0.01）. No significant adverse reactions were reported in either group. ConclusionThe "energy- inflammation- aging" network plays an important role in the pathological mechanism of hypertension patients. Qianyang Yuyin granules may delay the aging process by increasing patients' energy metabolism levels，reducing DNA oxidative damage，and maintaining the balance of inflammatory factors.

OBJECTIVE: To investigate the relationship between serum levels of fibroblast growth factor-23 (FGF-23), heparanase (HPSE) and early renal impairment (RI) in patients with multiple myeloma (MM). METHODS: A retrospective analysis was conducted on the clinical data of 125 MM patients who were initially diagnosed in the Department of Hematology of the First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology from June 2020 to June 2023. The patients were divided into RI group (>176.80 μmol/L) and non-RI group (≤176.80 μmol/L) based on their serum creatinine levels when diagnosed. The baseline data and laboratory indexes of the two groups were compared. The relationship between serum FGF-23, HPSE and early RI in MM patients was analyzed. RESULTS: Among 125 newly diagnosed MM patients, 33 cases developed early RI, accounting for 26.40%. The proportion of light chain type, blood urea nitrogen (BUN), blood uric acid, lactate dehydrogenase, FGF-23, and HPSE levels in RI group were higher than those in non-RI group (all P <0.05). There was no statistical significant difference in other data between the two groups (P >0.05). Multivariate logistic regression analysis showed that BUN, FGF-23 and HPSE were associated with early RI in MM patients (all P <0.05). The serum FGF-23 level was divided into Q1-Q4 groups by quartile, and the serum HPSE level was divided into q1-q4 groups. The correlation analysis showed that with the increase of serum FGF-23 and HPSE levels, the incidence of early RI increased (r =0.668, 0.592). Furthermore, logistic regression analysis showed that after controlling for confounding factors, elevated levels of serum FGF-23 and HPSE were still influencing factors for early RI in MM patients (OR>1, P <0.05). According to Pearson's linear correlation test, there was a positive correlation between serum FGF-23 level and HPSE level (r =0.373). CONCLUSION There is a certain correlation between serum levels of FGF-23, HPSE and early RI in MM patients, and the incidence of early RI is higher in patients with abnormally high levels of both.
Humans ; Multiple Myeloma/complications* ; Fibroblast Growth Factor-23 ; Retrospective Studies ; Fibroblast Growth Factors/blood* ; Glucuronidase/blood* ; Male ; Female ; Middle Aged ; Renal Insufficiency/blood* ; Aged

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones