OBJECTIVE To investigate the effects and mechanism of the Yishen paidu formula on renal fibrosis in rats with chronic renal failure （CRF） through the reactive oxygen species （ROS）/thioredoxin-interacting protein （TXNIP）/NOD-like receptor thermal protein domain associated protein 3 （NLRP3） pathway. METHODS Rats were randomly divided into control group， model group， Yishen paidu formula low-dose （Yishen paidu formula-L） group， Yishen paidu formula high-dose （Yishen paidu formula- H） group， Yishen paidu formula-H+pcDNA-NC group， and Yishen paidu formula-H+ pcDNA-TXNIP group， with 10 rats in each group. Except for control group， all other rats were fed a diet containing 0.5% adenine to establish a CRF model； the rats were then administered corresponding drugs or normal saline intragastrically or via tail vein， once daily， for 8 consecutive weeks. After the last administration， the levels of serum creatinine （Scr）， blood urea nitrogen （BUN）， ROS， superoxide dismutase （SOD）， malondialdehyde （MDA）， tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， and IL-1β were measured in each group. Pathological changes in renal tissue were observed， and the protein expression levels of Collagen Ⅲ， α-smooth muscle actin （α-SMA）， transforming growth factor-β1 （TGF-β1）， TXNIP and NLRP3 in renal tissue were detected. RESULTS Compared with model group， the renal histopathological damage and fibrosis of rats in Yishen paidu formula-L group and Yishen paidu formula-H group were significantly alleviated. The levels of Scr， BUN， ROS， MDA， TNF- α， IL-6 and IL-1β， and the protein expressions of Collagen Ⅲ， α-SMA， TGF-β1， TXNIP and NLRP3 were significantly decreased， while SOD levels were significantly increased （P＜0.05）. Moreover， the changes were more pronounced in the Yishen paidu formula-H group （P＜0.05）. Compared with Yishen paidu formula-H+pcDNA-NC group， above indexes of rats in Yishen paidu formula-H+pcDNA-TXNIP group were reversed significantly （P＜0.05）. CONCLUSIONS Yishen paidu formula can inhibit renal fibrosis in CRF rats by suppressing the ROS/TXNIP/NLRP3 pathway.

Objective: To develop a dual-branch deep learning framework for accurate multi-label classification of fundus diseases, addressing the key limitations of insufficient complementary feature extraction and inadequate cross-modal feature fusion in existing automated diagnostic methods. Methods: The fundus multi-label classification dataset with 12 disease categories (FMLC-12) dataset was constructed by integrating complementary samples from Ocular Disease Intelligent Recognition (ODIR) and Retinal Fundus Multi-Disease Image Dataset (RFMiD), yielding 6 936 fundus images across 12 retinal pathology categories, and the framework was validated on both FMLC-12 and ODIR. Inspired by the holistic multi-regional assessment principle of the Five Wheels theory in traditional Chinese medicine (TCM) ophthalmology, the dual-branch multi-label network (DBMNet) was developed as a novel framework integrating complementary visual feature extraction with pathological correlation modeling. The architecture employed a TransNeXt backbone within a dual-branch design: one branch processed red-green-blue (RGB) images to capture color-dependent features, such as vascular patterns and lesion morphology, while the other processed grayscale-converted images to enhance subtle textural details and contrast variations. A feature interaction module (FIM) effectively integrated the multi-scale features from both branches. Comprehensive ablation studies were conducted to evaluate the contributions of the dual-branch architecture and the FIM. The performance of DBMNet was compared against four state-of-the-art methods, including EfficientNet Ensemble, transfer learning-based convolutional neural network (CNN), BFENet, and EyeDeep-Net, using mean average precision (mAP), F1-score, and Cohen's kappa coefficient. Results: The dual-branch architecture improved mAP by 15.44 percentage points over the single-branch TransNeXt baseline, increasing from 34.41% to 44.24%, and the addition of FIM further boosted mAP to 49.85%. On FMLC-12, DBMNet achieved an mAP of 49.85%, a Cohen’s kappa coefficient of 62.14%, and an F1-score of 70.21%. Compared with BFENet (mAP: 45.42%, kappa: 46.64%, F1-score: 71.34%), DBMNet outperformed it by 4.43 percentage points in mAP and 15.50 percentage points in kappa, while BFENet achieved a marginally higher F1-score. On ODIR, DBMNet achieved an F1-score of 85.50%, comparable to state-of-the-art methods. Conclusion DBMNet effectively integrates RGB and grayscale visual modalities through a dual-branch architecture, significantly improving multi-label fundus disease classification. The framework not only addresses the issue of insufficient feature fusion in existing methods but also demonstrates outstanding performance in balancing detection across both common and rare diseases, providing a promising and clinically applicable pathway for standardized, intelligent fundus disease classification.

Health economics evidence plays an important role in linking clinical value evidence with health resource allocation decisions in the development of clinical practice guidelines. It can not only effectively balance clinical effectiveness and economic feasibility but also avoid forming "idealized" recommendations that are detached from the affordability of the healthcare system or the burden-bearing capacity of patients. To promote guideline developers to use health economics evidence more standardizedly and fully, this paper conducts an in-depth analysis of the current application status, existing challenges, access channels, and application processes of health economics evidence in current guidelines, and on this basis, puts forward considerations and suggestions for strengthening and standardizing the application of health economics evidence in China's clinical practice guidelines.

With the widespread application of deep learning technology in radiotherapy, increasing attention has been directed toward enhancing the precision and personalization of intelligent radiotherapy for osteosarcoma. This review summarizes the recent advances in the application of deep learning to osteosarcoma image preprocessing, automatic target volume delineation, dose prediction and treatment plan optimization, early efficacy assessment, and follow-up monitoring. Bottlenecks such as data sharing, model generalization, and interpretability are analyzed. This review aims to provide a comprehensive reference for technological iteration and clinical implementation in this field, as well as a scientific basis for the determination of future research directions and the development of standardized guidelines.

Objective To investigate the status of oral frailty(OF)in patients who underwent chemotherapy for lung cancer,identify key factors influencing OF,and develop a risk prediction model.Methods Using convenience sampling,431 lung cancer inpatient were recruited from three Tier-IIIA hospitals in Jiangsu Province between September and November 2024 as the training cohort.The patients were divided into OF and non-OF groups.Relevant data were compared between the two groups.Multifactorial logistic regression analysis was performed to determine factors that associated with OF,and a risk prediction model was created accordingly.Receiver operating characteristic(ROC)curve analysis was used to predict model performance.In December 2024,additional 185 patients from one other Tier-IIIA hospitals were recruited to validate the developed model.Results The prevalence of OF among lung-cancer patients undergoing chemotherapy was 58.93%.Following listed items were identified as the risk factors of OF(all P<0.05):older in age(OR=3.420),poor education(OR=0.030),brain metastasis(OR=7.880),high nutritional risk screening 2002 score(OR=1.550),elevated C-reactive protein(OR=1.100),and elevated lactate dehydrogenase(OR=1.010).ROC area under the curve(AUC)of the model was 0.860(95%CI:0.830-0.900)in modelling cohort and 0.840(95%CI:0.780-0.900)in validation cohort.Hosmer-Lemeshow goodness-of-fit test yielded χ 2=4.870,P=0.770 for the training set and χ 2=2.770,P=0.950 for the validation set.Conclusion The risk prediction model for OF developed in this study demonstrates a good predictive performance and can facilitate early identification of high-risk patients,thereby providing a scientific basis for clinical interventions.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Cannabidiol (CBD), a non-psychoactive cannabinoid, shows great promise in treating methamphetamine (METH) addiction. Nonetheless, the molecular target and the mechanism through which CBD treats METH addiction remain unexplored. Herein, CBD was shown to counteract METH-induced locomotor sensitization and conditioned place preference. Additionally, CBD mitigated the adverse effects of METH, such as cristae loss, a decline in ATP content, and a reduction in membrane potential. Employing an activity-based protein profiling approach, a target fishing strategy was used to uncover CBD's direct target. ATP5A1, a subunit of ATP synthase, was identified and validated as a CBD target. Moreover, CBD demonstrated the ability to ameliorate METH-induced ubiquitination of ATP5A1 via the D376 residue, thereby reversing the METH-induced reduction of ATP5A1 and promoting the assembly of ATP synthase. Pharmacological inhibition of the ATP efflux channel pannexin 1, blockade of ATP hydrolysis by a CD39 inhibitor, and blocking the adenosine A1 receptor (A1R) all attenuated the therapeutic benefits of CBD in mitigating METH-induced behavioral sensitization and CPP. Moreover, the RNA interference of ATP5A1 in the ventral tegmental area resulted in the reversal of CBD's therapeutic efficacy against METH addiction. Collectively, these data show that ATP5A1 is a target for CBD to inhibit METH-induced addiction behaviors through the ADO-A1R signaling pathway.

Objective To evaluate the clinical efficacy and safety of Compound Danshen Dripping Pills combined with Tirofiban in alleviating myocardial ischemia-reperfusion injury(MIRI)in patients with acute ST-segment elevation myocardial infarction(STEMI)after percutaneous coronary intervention(PCI).Methods Ninety-two patients with acute STEMI of qi stagnation and blood stasis syndrome who were admitted to the Chest Pain Center of Shunde Hospital,Guangzhou University of Chinese Medicine between March 2023 and October 2023 were equally randomized into a control group and a treatment group using a random number table,with 46 cases in each group.The control group received intracoronary loading dose of Tirofiban during PCI combined with postoperative intravenous micro-pump injection of Tirofiban,while the trial group additionally received Compound Danshen Dripping Pills orally,the treatment course lasted for 4 weeks.Before treatment or immediately after surgery and after 4 weeks of treatment,the two groups were observed in the changes in traditional Chinese medicine(TCM)syndrome scores,cardiac function parameters[including left ventricular ejection fraction(LVEF),cardiac output(CO),and left ventricular end-diastolic diameter(LVEDD)],and levels of inflammatory markers of C-reactive protein(CRP)and brain natriuretic peptide(BNP),as well as safety indicators such as liver and kidney function and coagulation parameters in both groups.The peak values of myocardial necrosis markers of creatine kinase-MB(CK-MB)and troponin I(cTnI)and other myocardial enzyme profiles between the two groups were compared.After treatment,the TCM syndrome efficacy of improvement,the therapeutic effect on improving ST-segment resolution(STR)of electrocardiogram,and the incidence of adverse cardiovascular events in both groups were assessed.Results(1)There were 3 patients dropping out during the trial,with a final total of 89 cases included in the efficacy analysis(44 cases in the control group and 45 cases in the trial group).(2)After 4 weeks of treatment,the total effective rate in the trial group was 95.56%(43/45)and that in the control group was 79.55%(35/44).Intergroup comparison by chi-square test showed that TCM syndrome efficacy in the trial group was significantly superior to that in the control group(P＜0.05).(3)After 4 weeks of treatment,the total effective rate for improving STR in the trial group was 93.33%(42/45)and that in the control group was 75.00%(33/44).Intergroup comparison(tested by chi-square test)demonstrated that the trial group had significantly stronger STR improvement efficacy than the control group(P＜0.05).(4)After 4 weeks of treatment,the serum levels of CRP and BNP in both groups were lower than those immediately after surgery(P＜0.05),and the trial group exhibited significantly greater reductions in both CRP and BNP levels than the control group(P＜0.01).(5)The peak values of myocardial necrosis markers of CK-MB and cTnI in the trial group were significantly lower than those in the control group,with statistically significant differences(P＜0.05).(6)After 4 weeks of treatment,the trial group showed significant improvements in LVEF and CO compared to immediate postoperative values(P＜0.05),while LVEDD demonstrated an improving trend without statistical significance(P＞0.05).The control group showed no significant improvements in LVEF,CO,or LVEDD(P＞0.05).The intergroup comparison revealed that the trial group had significantly better improvements in LVEF and CO than the control group(P＜0.05 or P＜0.01).(7)After 4 weeks of treatment,both groups showed reductions in the scores of chest pain,chest tightness,palpitations,emotional depression,hypochondriac distension,and dull complexion,as well as the total syndrome scores when compared to pretreatment values(P＜0.05),and the trial group presented significantly greater reductions than the control group(P＜0.05).(8)No statistically significant differences were shown in the parameters of liver/kidney function or coagulation between the two groups before and after treatment(P＞0.05).(9)The incidence of postoperative adverse cardiovascular events in the control group was 13.64%(6/44)and that in the trial group was 6.67%(3/45),and the intergroup comparison(tested by Fisher's exact test)showed no statistically significant difference(P＞0.05).Conclusion The combination therapy of Compound Danshen Dripping Pills and Tirofiban demonstrates significant efficacy in improving TCM syndromes,ST-segment elevation,myocardial necrosis markers,and cardiac function in STEMI patients after PCI,with good safety.

Based on the theory of the liver's"using bitter herbs to nourish or purge"from Huangdi Neijing,this paper systematically elucidates the theoretical foundation for treating functional constipation from liver.Focusing on the physiological characteristic of"liver desires to disperse"and the pathological manifestation of"liver bitterness and urgency,"combined with the"liver communicates with the large intestine"theory,this paper establishes a diagnostic and therapeutic framework for managing functional constipation by regulating liver function.The pathological evolution of functional constipation manifests in three distinct stages:in the early stage,liver qi stagnation leads to large intestine qi obstruction,where damaged by an excess of seven emotions resulting in symptoms such as difficult defecation,abdominal bloating,and hypochondriac pain;in the middle stage,liver depression transforms into fire,scorching bodily fluids to generate dryness,thereby creating a pathological interplay of stagnation,fire,and dryness,which is marked by anal heat,dry mouth,and yellow urine;in the late stage,yin deficiency in liver and kidney causes large intestine malnutrition,resulting in a complex pathological state where yin deficiency,collateral blockage,dryness accumulation,and blood stasis intertwine,clinically manifesting as pellet-like stools(resembling sheep feces)and soreness and weakness of the waist and knees.In treatment,the formula design follows the principle of"sweetness to relieve,acridity to tonify,and sourness to purge,"with treatment principles varying across stages.In the early stage,the focus is on dispersing liver and regulating qi,and unblocking the zang-fu viscera;in the middle stage,the priority shifts to clearing heat-fire,nourishing large intestine,and promoting fluid production;whereas,in the late stage,the emphasis lies on nourishing yin,unblocking collaterals,and promoting blood circulation.This staged treatment of functional constipation overcomes the limitations of solely focusing on nourishing large intestine and facilitating feces excretion,thereby advancing the treatment of different stages based on syndrome differentiation and personalized treatment.It provides theoretical support for improving patients' intestinal function and enhancing overall health outcomes.

Under the background of the integrated development of the Guangdong-Hong Kong-Macao Greater Bay Area,the demand for medical services from Hong Kong and Macao residents in Guangdong continues to grow.As the main force in pro-viding medical services in Guangdong,public hospitals play a crucial role.This article aims to explore the current situation of the development of medical services for Hong Kong and Macao residents in Guangdong and propose development strategies from the perspective of hospitals to contribute to the integrated development of the Greater Bay Area.The SWOT method is used to system-atically evaluate the strengths,weaknesses,opportunities,and threats of Guangdong public hospitals in the development of medi-cal services for Hong Kong and Macao residents.A SWOT matrix is then constructed to formulate development countermeasures.The analysis shows that Guangdong public hospitals have advantages such as convenient transportation,cultural affinity,abundant medical resources,high service efficiency,and relatively low costs.However,they also face challenges such as inadequate cover-age of cross-border medical insurance,immature specialized services,inconsistent service standards,and insufficient exploration of cross-border medical care.At the same time,there are opportunities provided by national strategic support and strong market demand,while fierce market competition and slow integration of medical regulations among the three regions pose external threats.Based on the analysis,this article proposes countermeasures and suggestions,including strengthening publicity and innovative in-dustry cooperation,phased development of business,striving for policy coverage,enhancing business coordination,accelerating cooperation with the Hong Kong and Macao in medical care,and promoting international accreditation of hospitals.These sugges-tions provide decision-making references for the development of medical services for Hong Kong and Macao residents in Guang-dong's public hospitals.