Objective To explore the efficacy and safety of converting the triple immunosuppressive regimen of tacrolimus (Tac) + mycophenolate mofetil (MMF) + prednisone (Pred) to a quadruple regimen of low-dose sirolimus (SRL) + low-dose Tac + MMF + Pred at 3 to 6 months after expanded criteria donor (ECD) kidney transplantation. Methods A single-center, retrospective, donor-matched controlled study included 22 ECD kidney transplant recipients from September 2021 to June 2024. Two recipients from the same donor kidneys were respectively assigned to the SRL group and the conventional triple regimen control group. The main outcome measures were the differences in serum creatinine (Scr), estimated glomerular filtration rate (eGFR), and adverse events before the regimen conversion and after conversion during the 1, 3, 6, and 12-month follow-up. Results There were no statistically significant differences in baseline characteristics between the two groups. In the SRL group, Scr decreased and eGFR increased starting from 3 months after conversion, and this was superior to the control group starting from 6 months(all P < 0.05). There were no statistically significant differences in the incidence of rejection reactions, pulmonary infections, hyperlipidemia and proteinuria between the two groups after conversion and during the 12-month follow-up (all P > 0.05). Conclusions For ECD kidney transplant recipients, converting the triple regimen to the SRL quadruple regimen at 3 to 6 months after transplantation may improve the function of the transplanted kidney without increasing the risk of adverse events.

ObjectiveThis paper aims to investigate the distribution patterns of traditional Chinese medicine syndromes in patients with chronic hepatitis B （CHB） comorbid with metabolically associated fatty liver disease （MAFLD） and analyze their correlation with clinical characteristics and the progression of liver fibrosis. MethodsA cross-sectional study method was employed， and 506 patients with CHB comorbid with MAFLD who attended the Hepatology Outpatient Department of Public Health Clinical Center of Chengdu from June 2024 to December 2024 were enrolled. General information， traditional Chinese medicine syndromes information， laboratory indicators， and imaging examination results were collected using case report forms （CRF）. Tongue images of patients were acquired using a tongue diagnosis instrument， and tongue feature parameters were extracted using computer image processing technology. Frequency analysis， factor analysis， and cluster analysis， and other methods were used to explore syndrome categories and distribution patterns. Non-parametric tests were used to compare the differences in clinical characteristics among different syndromes. Univariate and multivariate logistic regression analyses were performed to investigate the correlation between traditional Chinese medicine syndromes and the progression of liver fibrosis. ResultsThe main traditional Chinese medicine syndromes in patients with CHB comorbid with MAFLD were mainly dominated by damp-heat accumulation syndrome， liver stagnation and spleen deficiency syndrome， and phlegm-blood stasis syndrome， with damp-heat accumulation syndrome accounting for the highest proportion （41.89%）. Compared with those without damp-heat accumulation syndrome， patients with damp-heat accumulation syndrome had significantly lower tongue proper H value， tongue coating H value， and tongue coating a^* value （P<0.05）， significantly higher tongue coating b^* value （P<0.05）， significantly increased levels of white blood cell （WBC）， red blood cell （RBC）， hemoglobin （HGB）， and glucose （GLU）， increased CAP values （P<0.05）， a higher proportion of males （P<0.05）， and a younger age （P<0.05）. Univariate and multivariate logistic regression analyses show that age， hepatitis B surface antigen （HBsAg）， diabetes， and damp-heat accumulation syndrome are independent risk factors for liver fibrosis （P<0.05）， and that damp-heat accumulation syndrome is predominantly distributed in liver fibrosis stage F0-F1. ConclusionDamp-heat accumulation syndrome is a typical syndrome in patients with CHB comorbid with MAFLD， which is significantly associated with enhanced inflammatory response， metabolic disorders， and early liver fibrosis， and is a key link in disease progression. Clinical attention and early intervention are needed.

Accurate prediction of drug-target interactions (DTIs) plays a pivotal role in drug discovery, facilitating optimization of lead compounds, drug repurposing and elucidation of drug side effects. However, traditional DTI prediction methods are often limited by incomplete biological data and insufficient representation of protein features. In this study, we proposed KG-CNNDTI, a novel knowledge graph-enhanced framework for DTI prediction, which integrates heterogeneous biological information to improve model generalizability and predictive performance. The proposed model utilized protein embeddings derived from a biomedical knowledge graph via the Node2Vec algorithm, which were further enriched with contextualized sequence representations obtained from ProteinBERT. For compound representation, multiple molecular fingerprint schemes alongside the Uni-Mol pre-trained model were evaluated. The fused representations served as inputs to both classical machine learning models and a convolutional neural network-based predictor. Experimental evaluations across benchmark datasets demonstrated that KG-CNNDTI achieved superior performance compared to state-of-the-art methods, particularly in terms of Precision, Recall, F1-Score and area under the precision-recall curve (AUPR). Ablation analysis highlighted the substantial contribution of knowledge graph-derived features. Moreover, KG-CNNDTI was employed for virtual screening of natural products against Alzheimer's disease, resulting in 40 candidate compounds. 5 were supported by literature evidence, among which 3 were further validated in vitro assays.
Alzheimer Disease/drug therapy* ; Biological Products/therapeutic use* ; Humans ; Neural Networks, Computer ; Machine Learning ; Drug Discovery/methods* ; Algorithms ; Drug Evaluation, Preclinical/methods*

Objective To explore clinical effect of accessory scaphoid bone fusion in treating type Ⅱ painful accessory scaphoid bone.Methods A retrospective analysis was performed on 26 patients with type Ⅱ painful accessory navicular bone treated by accessory navicular bone fusion from January 2012 to June 2022,including 1 male and 25 females,aged from 18 to 70 years old with an average of(44.61±16.32)years old;10 patients with type Ⅱ A and 16 patients with type Ⅱ B;20 patients with simple fusion and 6 patients with fusion plus calcaneal translocation osteotomy.Changes of Meary angle,Pitch angle,an-teroposterior talar-first metatarsal angle(T1MA),talonavicular coverage angle(TCA),lateral talocalcaneal angle(LTCA)be-fore operation and 6 months after operation were observed and compared,and American Orthopedic Foot and Ankle Society(AOFAS)foot and ankle score and visual analogue scale(VAS)were used to explore clinical effect.Results All 26 patients were followed up for 7 to 24 months with an average of(10.72±3.94)months.Meary angle,Pitch angle,T1MA,TCA and LTCA were improved from(9.20±2.57)°,(16.45±3.57)°,(33.34±5.02)°,(22.42±5.86)°,(48.89±4.43)° before opertaion to(3.33±1.06)°,(22.33±4.56)°,(23.89±3.48)°,(11.83±2.67)°,(36.50±3.50)° at 6 months after operation,the difference were statistically significant(P＜0.01).Postoperative AOFAS foot and ankle score were(86.24±4.33)and(93.18±6.02)for type Ⅱ A and type Ⅱ B at 6 months,which were significantly improved compared with those for type Ⅱ A and type Ⅱ B before op-eration(67.34±6.55)and(65.12±9.51),and the difference was statistically significant(P＜0.01);20 patients got excellent re-sult,5 good and 1 poor.Preoperative VAS of type ⅡA(5.67±1.58)and type Ⅱ B(5.77±1.49)were improved to(2.13±1.01)and(1.43±0.68)at 6 months after operation,with statistical significance(P＜0.01).Conclusion Fusion of accessory navicular bone in patients with type Ⅱ painful accessory navicular bone combined with internal calcaneal osteotomy in patients with par-tial calcaneal valvaration could effectively correct flat foot deformity and relieve pain,and could be used as a clinical treatment for painful accessory navicular bone.

Aim To investigate the therapeutic effects of corylifol A(CYA)on Lewis lung carcinoma(LLC)cachexia mice and its ameliorating effects on myotube atrophy induced by LLC cell-conditioned medium(LLC CM)in vitro,and to explore the mechanisms.Methods The cancer cachexia was induced by subcu-taneous inoculation of LLC cells to C57BL/6J mice.The effects of CYA(10,20 mg·kg-1·d-1,i.p.)on the cachexia symptoms and survival time of cachexia mice were observed.The effects of 2.5 or 5 μmol·L-1 CYA on myotube atrophy of C2C12 induced by LLC CM were observed.The effects of CYA on its pos-sible target the serine/threonine-protein kinase TAO1(TAOK1)and downstream signaling pathways were detected using Western blot.The influence of TAOK1 knockout on the ameliorating effects of CYA on myo-tube atrophy was observed.Results CYA could sig-nificantly prolong the survival time of tumor-bearing mice and ameliorate the muscle atrophy associated with LLC.The effects of CYA on myotube atrophy are relat-ed to its regulation of TAOK1.The effects of CYA could be reduced by knockout of TAOK1.Conclusions CYA improves the survival of LLC cachexia mice and ameliorates the related skeletal muscle atrophy.The mechanism of CYA is related to its inhibition on TAOK1 and downstream signaling pathways.

Objective:To explore the expression regulation of lipid metabolism gene ABHD5 in testes.Methods:Differential gene analysis was performed by integrating databases of TCGA and GTEx to identify the target gene ABHD5.The expression trends of ABHD5 gene in testicular carcinoma tissue were analyzed.Human testis single-cell atlases were obtained from the Human Protein Atlas and Male Health Atlas databases to determine the expression distribution of ABHD5 across different testicular cell types.Additionally,the GTEx database was utilized to visualize the expression pattern of ABHD5 in the testis,thereby enhancing the understanding of its transcriptional profile.The relationship between ABHD5 expression and age was assessed through integrated database analysis.Western blotting and immunofluorescence were performed to detect differential expressions of ABHD5 in testicular tissues of young and aged mice respectively.Results:The TCGA database indicated that the expression of ABHD5 in human testicular carcinoma tissue was significantly lower than that in normal testicular tissue which showed a negative correlation with patient survival.ABHD5 was highly ex-pressed in germ cells of the testis reveaked from Human Protein Atlas and Male Health Atlas databases.The stability of ABHD5 protein was crucial for testicular tissue,and its expression decreased with age.Furthermore,Western blot and immunofluorescence staining demonstrated that ABHD5 expression in the testicular tissue of aged mice was significantly lower than that in young mice.Conclu-sion:ABHD5 plays an important role in testicular tissue,and may be inseparable from testicular tumors and reproductive aging.How-ever,its mechanism of action remains to be further studied.

Objective To explore clinical effect of accessory scaphoid bone fusion in treating type Ⅱ painful accessory scaphoid bone.Methods A retrospective analysis was performed on 26 patients with type Ⅱ painful accessory navicular bone treated by accessory navicular bone fusion from January 2012 to June 2022,including 1 male and 25 females,aged from 18 to 70 years old with an average of(44.61±16.32)years old;10 patients with type Ⅱ A and 16 patients with type Ⅱ B;20 patients with simple fusion and 6 patients with fusion plus calcaneal translocation osteotomy.Changes of Meary angle,Pitch angle,an-teroposterior talar-first metatarsal angle(T1MA),talonavicular coverage angle(TCA),lateral talocalcaneal angle(LTCA)be-fore operation and 6 months after operation were observed and compared,and American Orthopedic Foot and Ankle Society(AOFAS)foot and ankle score and visual analogue scale(VAS)were used to explore clinical effect.Results All 26 patients were followed up for 7 to 24 months with an average of(10.72±3.94)months.Meary angle,Pitch angle,T1MA,TCA and LTCA were improved from(9.20±2.57)°,(16.45±3.57)°,(33.34±5.02)°,(22.42±5.86)°,(48.89±4.43)° before opertaion to(3.33±1.06)°,(22.33±4.56)°,(23.89±3.48)°,(11.83±2.67)°,(36.50±3.50)° at 6 months after operation,the difference were statistically significant(P＜0.01).Postoperative AOFAS foot and ankle score were(86.24±4.33)and(93.18±6.02)for type Ⅱ A and type Ⅱ B at 6 months,which were significantly improved compared with those for type Ⅱ A and type Ⅱ B before op-eration(67.34±6.55)and(65.12±9.51),and the difference was statistically significant(P＜0.01);20 patients got excellent re-sult,5 good and 1 poor.Preoperative VAS of type ⅡA(5.67±1.58)and type Ⅱ B(5.77±1.49)were improved to(2.13±1.01)and(1.43±0.68)at 6 months after operation,with statistical significance(P＜0.01).Conclusion Fusion of accessory navicular bone in patients with type Ⅱ painful accessory navicular bone combined with internal calcaneal osteotomy in patients with par-tial calcaneal valvaration could effectively correct flat foot deformity and relieve pain,and could be used as a clinical treatment for painful accessory navicular bone.

Inflammatory response is a common feature of many acute and chronic diseases,which involves in activation of various cell types.Similar to tumor cells,inflammatory response is regulated by glucose metabolic reprogramming.Cells involved in pro-inflammatory response,such as M1 macrophages,Th1 and Th17 lymphocytes,must generate energy rapidly through glycolysis transformed by glucose metabolic reprogramming to promote inflammation,while cells involved in immune regulation and anti-inflam-matory response,such as regulatory T cells and M2 macrophages,preferentially use fatty acid oxidation and oxidative phosphorylation as a main source for energy production.This article systematically reviews the role of glucose metabolic reprogramming in different stages of inflammatory response,as well as the various molecular mechanisms of glucose metabolic reprogramming in inflammatory response,including activation or inhibition of signaling pathways,epigenetic regulation,post-transcriptional regulation and post-translational modification,which aims to provide a reference for exploring the specific regulatory mechanisms of glucose metabolic reprogramming on inflammatory response and the therapeutic targets of inflammatory-related diseases.

Medical therapy and surgical intervention are the two primary approaches for treating myocardial bridge.However,there remains controversy regarding the use of coronary artery bypass grafting(CABG)and myocardial bridge unroofing.Here,we report a case of myocardial infarction following CABG in a patient with a myocardial bridge.The patient was admitted to Lanzhou First Peopie's Hospital with persistent chest pain,chest tightness,and shortness of breath lasting 2 hours.Physical examination revealed no significant abnormalities.Electrocardiography(ECG)indicated extensive anterior wall myocardial infarction.Laboratory findings showed myoglobin levels of 140.1 ng/ml and troponin Ⅰ levels of 2.59 ng/ml,with no other significant abnormalities.The initial diagnosis was acute extensive anterior wall myocardial infarction.Emergency coronary angiography revealed a myocardial bridge in the mid-segment of the left anterior descending artery(LAD).Emergency CABG using the left internal mammary artery to the LAD was performed,leading to symptomatic improvement,and the patient was discharged in stable condition.However,the patient experienced a recurrent myocardial infarction seven years post-surgery and received secondary preventive medical therapy.The patient is currently under ongoing follow-up care.CABG is an effective treatment for myocardial bridge.However,based on the case reported in this study,we recommend careful evaluation of whether a patient may benefit from CABG.

Purpose To explore the application value of magnetic resonance feature tracking to assess early heart failure in different rat models.Materials and Methods Fifty male SD rats were randomly divided into four groups:the control group(8 rats),the isoproterenol high dose(ISO-H)group(14 rats),the isoproterenol low dose(ISO-L)group(14 rats)and the coronary artery ligation surgery(myocardial infarction,MI)group(14 rats).The ISO-H group received intraperitoneal injections of ISO at 100 mg/kg once a week for two consecutive weeks.The ISO-L group received continuous intraperitoneal injections of ISO at 5 mg/(kg·d)for 14 days.The MI group underwent coronary ligation to establish a heart failure rat model.Scans using a 7T cardiac MRI cine sequence were performed after two weeks and four weeks.Heart function parameters and myocardial strain parameters were obtained using CVI 42 software.Serum markers of myocardial injury,including creatine kinase,creatine kinase-MB,lactate dehydrogenase and α-hydroxybutyric dehydrogenase levels,were measured.HE staining and Masson staining were used to detect myocardial pathological changes.Results Compared with the control group,the ISO-H group,ISO-L group and MI group showed significant changes in left ventricular ejection fraction(t=-2.387,P=0.04;t=5.622,P<0.001;t=17.715,P<0.001)and overall radial strain(t=-4.570,P=0.001;t=6.587,P<0.001;t=10.649,P<0.001)after two weeks.Compared with the control group,the ISO-H group,ISO-L group and MI group showed varying degrees of reduction in left ventricular ejection fraction(t=4.834,P=0.001;t=10.325,P<0.001;t=26.286,P<0.001)and overall radial strain(t=3.890,P=0.003;t=9.547,P<0.001;t=13.751,P<0.001)after four weeks.The serum markers of myocardial injury,including creatine kinase,creatine kinase-MB,lactate dehydrogenase and α-hydroxybutyric dehydrogenase levels,were significantly elevated(t=-93.373--11.019,P<0.001),and pathological staining revealed that all model groups exhibited varying degrees of myocardial cell hypertrophy,necrosis and interstitial fibrosis compared with the control group.Conclusion Magnetic resonance feature tracking has guiding significance for the dynamic monitoring,early diagnosis and prognosis assessment of heart failure in different rat models.