Diabetic nephropathy （DKD）， as a common microvascular complication of diabetes mellitus （DM）， is a major cause of end-stage renal disease （ESRD）. Its clinical manifestations include increased urinary protein excretion， thickening of the glomerular basement membrane， and renal tubulointerstitial fibrosis. The pathogenesis of DKD is complex and involves multiple factors， including disordered glucose metabolism， hemodynamic alterations， and oxidative stress. Although modern medical approaches can alleviate certain symptoms， they still have limitations such as insufficient therapeutic targeting and prominent adverse effects. The transforming growth factor-β/Smad （TGF-β/Smad） signaling pathway is not only a tissue fibrosis pathway that has attracted considerable attention in recent years， but also regulates multiple protein molecules， including the glomerular podocyte slit diaphragm protein Podocin， interleukin-1β （IL-1β）， and superoxide dismutase （SOD）， thereby participating in various pathological processes and ultimately mediating renal injury. Flavonoid compounds， owing to their sustained pharmacological effects， broad spectrum of action， and high safety profile， have become ideal candidates for targeted therapy research in DKD. Existing studies have shown that these compounds can exert inhibitory effects on renal fibrosis， alleviate inflammatory responses， protect podocytes， and reduce oxidative stress by regulating the interactions between the TGF-β/Smad signaling pathway and the aforementioned protein molecules， thereby maintaining renal structure and function， reducing proteinuria， and significantly improving DKD lesions. This review briefly outlines the composition and functions of the TGF-β/Smad signaling pathway， elucidates the mechanisms by which this pathway regulates DKD， and focuses on summarizing major studies from the past decade on flavonoid-based interventions in DKD through targeted inhibition of the TGF-β/Smad signaling pathway. Furthermore， it discusses the considerable therapeutic potential of flavonoids in the treatment of this disease， aiming to provide a scientific basis for future clinical prevention and treatment of DKD and to promote the development of targeted drugs.

OBJECTIVE To explore the characteristics and influential factors of pharmaceutical clinic service demands， providing evidence for optimizing pharmaceutical service models and facilitating pharmaceutical service models of pharmacist role transformation. METHODS A cross-sectional survey design was adopted， and 410 outpatient participants were selected from Fudan University Shanghai Cancer Center through convenience sampling for questionnaire administration from February to May 2025. Kano model was applied to analyze the demand attributes of 25 pharmaceutical services， while questionnaires were used to assess patients’ awareness and demand status. Subgroup analyses were conducted based on key demographic variables such as gender， age， educational attainment， and economic burdens， to SACA- systematically examine the differences in Kano attribute classification among patients in each subgroup. RESULTS The awareness rate of pharmaceutical outpatient services among patients was only 14.63%， yet those who were aware demonstrated a significantly higher demand rate for such services compared to those who were unaware （P＜0.001）. The demand for pharmaceutical clinic services exhibited a hierarchical characteristic： twelve items were identified as attractive attributes （e. g.， providing suggestions for more affordable treatment options， offering online consultation services， etc.）， five items as expected attributes （e.g.， having a good attitude and being able to patiently answer your questions， etc.）， three items as must-have attributes （e.g.， providing guidance on medication dosage and usage， providing guidance on medication precautions， etc.）， five items as indifferent attributes （e.g.， providing treatment plan recommendations based on the patient’s condition）. There were zero items classified as reverse attribute. Subgroup analysis revealed that female patients showed greater concern for “neat and clean attire of medical staff” than male patients （P＜0.001）； patients under 60 years of age demonstrated stronger demand for “providing treatment plan recommendations based on patients’ conditions” compared to patients aged 60 or above （P＝0.016）； those with below high school education placed greater emphasis on “providing guidance on medication precautions” compared to those with a high school education or above （P＝0.011）； patients with lower economic burdens exhibited stronger preferences for “neat and clean attire of medical staff ” （P＝0.002）. CONCLUSIONS The public awareness rate of pharmaceutical clinic services is considerably low； however， those who are aware of such services demonstrate significantly higher demand. The medication safety-related services and convenience-oriented demands should be prioritized in the development of pharmaceutical clinics. Moreover， the study also revealed that factors such as gender， age， educational level， and economic burdens exert significant influences on patients’ service demands.

The pain-evoked potential electroencephalogram (EEG) is an effective electrophysiological indicator for pain assessment, yet its extraction is challenging due to interference from background activity and involuntary blinks. Although existing blink artifact-removal methods show efficacy, they face limitations such as the need for reference signals, neglect of individual differences, and reliance on user input, hindering their practical application in clinical pain assessments. In this paper, we propose a novel framework applying adaptive quadrature mirror filter banks (AQMFB) with discrete wavelet transform (DWT) to remove blink artifacts in pain EEG. Unlike traditional DWT methods that apply fixed wavelets across subjects, our method adapts wavelet construction based on the characteristics of EEG. Experimental results demonstrate that AQMFB-DWT outperforms four leading methods in removing blink artifacts with minimal distortion of pain information, all within an acceptable processing time. This technique is a valuable preprocessing step for enhancing the extraction of pain-evoked potentials.
Humans ; Artifacts ; Blinking/physiology* ; Electroencephalography/methods* ; Pain/diagnosis* ; Male ; Wavelet Analysis ; Adult ; Female ; Evoked Potentials/physiology* ; Young Adult ; Brain/physiopathology* ; Pain Measurement/methods* ; Signal Processing, Computer-Assisted

By combing the application and funding situation of general， young scholar and regional scholar programs from National Natural Science Foundation of China（NSFC） in field of integrated traditional Chinese and western medicine in 2023， this paper summarizes the distribution of supporting units， application and funding hotspots， and the problems of application and funding projects in this discipline， in order to provide a reference for applicants and supporting organizations to understand the hotspot dynamics and reporting requirements of the discipline. In 2023， the discipline of integrated traditional Chinese and western medicine received a total of 2 793 applications， and there were 1 254 applications for general programs， 1 278 applications for young scholar programs， and 261 applications for regional scholar programs. The amounts of project funding obtained by the three were 145， 164 and 35， respectively， and the funding rates were 11.56%， 12.83% and 13.41% in that order. From the situation of obtaining funding， the age distribution of the project leaders who obtained funding for the general， young scholar and regional scholar programs were mainly distributed in the age of 40-46， 30-34， 38-44 years， respectively. Within the supported programs， the Chinese medicine affiliations accounted for 55.52%. With respect to research subjects， the proportion of one single Chinese herbs， or monomers， or extracts accounted for 29.4%， but the proportion of Chinese herb pairs or prescriptions accounted for 47.1%. Research hotspots included ferroptosis， bile acid metabolism， macrophages， mitochondria， microglia， exosomes， intestinal flora， microecology and so on. The current research mainly focused on the common key problems of the advantageous diseases of Chinese and western integrative medicine， but still need to be improved in the basic theories of Chinese and western medicine and multidisciplinary cross-disciplinary research.

Objective To establish the theories and methods for the compatibility of Chinese patent medicines in pre-scription review.Methods Based on the prescription combination theory and the classics literatures of traditional Chinese med-icine,the methods of prescription suitability review for the compatibility of Chinese patent medicines were discussed.Results Based on the examples of the compatibility of Chinese patent medicines,five basic principles of combined Chinese patent medi-cines and the key points for reviewing the combined Chinese patent medicines dosage form were discussed in detail.Conclusion The methods for the compatibility of Chinese patent medicines prescription review have been established,which can provide a theoretical reference for the review of combined Chinese patent medicines prescriptions.

Humans ; Tranexamic Acid/therapeutic use* ; Arthroplasty, Replacement, Knee ; Antifibrinolytic Agents/therapeutic use* ; Blood Loss, Surgical ; Postoperative Hemorrhage

ObjectiveTo explore the protective effect and mechanism of Yangxin Dingji capsules on isoproterenol （ISO）-induced ventricular arrhythmia in SD rat cardiomyocytes based on the transforming growth factor-β activated kinase 1 （TAK1）-mitogen-activated protein kinase kinase 3 （MKK3）-p38 mitogen-activated protein kinase （p38 MAPK） signaling pathway. MethodFifty male SPF-grade SD rats were randomly divided into a normal group， a model group， a propranolol group， a low-dose Chinese medicine group， and a high-dose Chinese medicine group. The ventricular arrhythmia model was constructed using the ISO "6+1" method. The propranolol group received propranolol at 0.015 g·kg^-1·d^-1. The Chinese medicine groups received Yangxin Dingji capsules at doses of 0.5、 2 g·kg^-1·d^-1， respectively. The normal and model groups were given an equal volume of 0.9% NaCl solution. Electrocardiogram （ECG） changes in SD rats were recorded using the BL-420F biological function experimental system. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in the heart. Serum levels of cardiac troponin I （cTnI）， creatine kinase-MB （CK-MB）， interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and transforming growth factor-β₁ （TGF-β₁） were measured using enzyme-linked immunosorbent assay （ELISA）. The mRNA expression of IL-1β and TNF-α was assessed using real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. Reactive oxygen species （ROS） expression was detected using immunofluorescence. Protein expression levels of TAK1， phosphorylated TAK1 （p-TAK1）， MKK3， phosphorylated MKK3 （p-MKK3）， p38 MAPK， phosphorylated p38 MAPK （p-p38 MAPK）， nuclear factor-κB （NF-κB）， phosphorylated NF-κB （p-NF-κB）， IL-1β， and TNF-α were measured using Western blot or immunohistochemistry. ResultCompared with normal group， the model group showed significant ventricular arrhythmia in ECG， with an increased arrhythmia score （P<0.01）. Pathological damage to myocardial tissue was evident， and serum levels of cTnI， CK-MB， IL-1β， TNF-α， and TGF-β₁ were elevated （P<0.01）. The mRNA and protein expression of IL-1β and TNF-α in myocardial tissue was also increased （P<0.01）. ROS level and protein expression of p-TAK1， p-MKK3， p-p38 MAPK， and p-NF-κB were elevated in myocardial tissue （P<0.01）. In the propranolol and Chinese medicine groups， the incidence of sustained ventricular tachycardia （SVT） and arrhythmia scores were significantly reduced compared to model group （P<0.05， P<0.01）. Pathological damage to cardiomyocytes was alleviated， and levels of myocardial injury markers and inflammatory factors in serum and myocardial tissue were decreased. The ROS level in myocardial tissue was also reduced （P<0.01）， with a noticeable reduction in related molecules in the p38 MAPK pathway （P<0.05， P<0.01）. ConclusionThe expression of p38 MAPK pathway molecules was up-regulated in myocardial tissue of ISO-induced ventricular arrhythmia rats. Yangxin Dingji capsules may inhibit cardiac inflammation damage by regulating the expression of related molecules in the p38 MAPK pathway， thereby exerting a protective effect on myocardial cells， with TAK1 being a potential target.

Objective To investigate the basic information of human immunodeficiency virus/acquired immune deficiency syndrome(HIV/AIDS)patients who infected with Epstein-Barr virus(EBV)or human Cytomegalovirus(HCMV),collect the relevant clinical immunological data and analyze the influencing factors.Method A total of 1 093 HIV/AIDS patients treated in the First Hospital of Changsha from January to December 2022 and underwent EBV and HCMV screening were collected.Flow cytometry was used to detect the CD4+T lymphocytes.Fluorescence quantitative PCR was applied for HIV-RNA,EBV-DNA,and HCMV-DNA testing.Statistical analysis was carried out by using SPSS 27.0,and logistic regression was used to analyze the risk factors of HIV/AIDS patients complicated with viral infection.Results Among 1 093 HIV/AIDS patients,the positive rates of EBV-DNA and HCMV-DNA were 48.22%(527/1 093)and 19.03%(208/1 093),respectively.As the number of CD4+T lymphocytes increased,the positive rates of EBV-DNA and HCMV-DNA decreased,and the differences was statistically significant(χ2=39.50,143.0,all P<0.001).As the level of HIV-RNA increased,the positive rates of EBV-DNA and HCMV-DNA increased,and the differences were statistically significant(χ2=46.18,124.3,all P<0.001).The patients receiving antiretroviral therapy(ART)significantly decreased the positive rates of EBV-DNA and HCMV-DNA(χ2=30.60,96.59,all P<0.001).There was a significant negative correlation between the number of CD4+T lymphocytes and the level of HIV-RNA(r=-0.49,P<0.001).Logistic regression analysis showed that the CD4+T lymphocyte count<200/μl(OR=1.46,95%CI:1.02～2.08,P=0.037),HIV-RNA load>200 copies/ml(OR=1.70,95%CI:1.18～2.44,P=0.004)and the age>30 years old(OR=2.15,95%CI:1.44～3.19,P<0.001)were risk factors for HIV/AIDS patients infected with EBV.Without regularly receiving ART(OR=1.83,95%CI:1.10～3.02,P=0.019),HIV-RNA load>200 copies/ml(OR=2.56,95%CI:1.50～4.35,P<0.001)and the CD4+T lymphocyte count<200/μl(OR=4.61,95%CI:2.57～8.28,P<0.001)were risk factors for HCMV infection in HIV/AIDS patients.Conclusion To reduce the possibility of opportunistic infection in HIV/AIDS patients,the surveillance of EBV and HCMV and regular ART should be strengthened,especially when the number of CD4+T lymphocytes decreases(<200/μl),the level of HIV RNA increases(>200 copies/ml)or the age>30 years old.

Objective: To investigate the association of primary tumor site with prognosis in vulvar cancer, stratified by vulvar squamous cell carcinoma (SCC) and non-SCC histological types. Methods: This population-based retrospective study enrolled patients with vulvar cancer from the Surveillance, Epidemiology, and End Results database between January 2000 and December 2018. The primary outcome was cancer-specific survival (CSS). The prognostic difference between labium majus, labium minus and clitoris groups was investigated using Kaplan–Meier analyses and Cox proportional hazards regression analyses. Results: A total of 3,465 eligible patients with vulvar cancer were included with a mean age of 54.5 years. Among the 1,076 (31.1%) patients with non-SCC, the multivariate Cox regression analyses showed that labium minus-sited disease (hazard ratio [HR]=1.85; 95% confidence interval [CI]=1.27–2.71; p=0.001) and clitoris-sited disease (HR=2.37; 95% CI=1.47–3.85;p<0.001) were significantly associated with worse CSS, compared with labium majus-sited disease. However, among the 2,389 (68.9%) patients with SCC, no significant association of primary tumor site with CSS was found (p>0.05). Kaplan–Meier analyses also showed that the primary tumor site had a significant prognostic effect in vulvar non-SCC (p<0.001) but not in vulvar SCC (p=0.330). Conclusion Among vulvar non-SCC, patients with labium minus-sited disease had a significantly worse prognosis than those with labium majus-sited disease, and a significantly better prognosis than those with clitoris-sited disease. Gynecologic oncologists should consider the prognostic effect of primary tumor site in vulvar non-SCC, and make optimal, personalized treatment and surveillance strategies based on different primary tumor sites.

Objective: To investigate the association of primary tumor site with prognosis in vulvar cancer, stratified by vulvar squamous cell carcinoma (SCC) and non-SCC histological types. Methods: This population-based retrospective study enrolled patients with vulvar cancer from the Surveillance, Epidemiology, and End Results database between January 2000 and December 2018. The primary outcome was cancer-specific survival (CSS). The prognostic difference between labium majus, labium minus and clitoris groups was investigated using Kaplan–Meier analyses and Cox proportional hazards regression analyses. Results: A total of 3,465 eligible patients with vulvar cancer were included with a mean age of 54.5 years. Among the 1,076 (31.1%) patients with non-SCC, the multivariate Cox regression analyses showed that labium minus-sited disease (hazard ratio [HR]=1.85; 95% confidence interval [CI]=1.27–2.71; p=0.001) and clitoris-sited disease (HR=2.37; 95% CI=1.47–3.85;p<0.001) were significantly associated with worse CSS, compared with labium majus-sited disease. However, among the 2,389 (68.9%) patients with SCC, no significant association of primary tumor site with CSS was found (p>0.05). Kaplan–Meier analyses also showed that the primary tumor site had a significant prognostic effect in vulvar non-SCC (p<0.001) but not in vulvar SCC (p=0.330). Conclusion Among vulvar non-SCC, patients with labium minus-sited disease had a significantly worse prognosis than those with labium majus-sited disease, and a significantly better prognosis than those with clitoris-sited disease. Gynecologic oncologists should consider the prognostic effect of primary tumor site in vulvar non-SCC, and make optimal, personalized treatment and surveillance strategies based on different primary tumor sites.