OBJECTIVE To investigate the effects of Tripterygium wilfordii multiglycoside （TWM） on renal injury in diabetic nephropathy （DN） rats through tumor protein p53/microRNA-214 （miR-214）/UNC-51-like kinase 1 （ULK1） axis. METHODS Male SD rats were randomly divided into normal group （n＝6） and modeling group （n＝28）； the modeling group was fed with high fat and high glucose plus intraperitoneal injection of streptozotocin to establish DN model. The modeled rats were randomly divided into model group， valsartan group [8.33 mg/（kg·d）] and TWM group[6.25 mg/（kg·d）]， with 8 rats in each group. Rats in each group were gavaged with the corresponding medication or normal saline， once a day， for 6 consecutive weeks. After the last medication， liver and renal function indexes [24 h urinary total protein （24 h-UTP）， blood urea nitrogen （BUN）， serum creatinine （SCr）， albumin （ALB）， alanine transaminase （ALT）]， blood lipid indexes （triglycerides， total cholesterol） and blood glucose index （fasting blood glucose） in urine/blood sample of rats were detected in each group. Renal pathologic change was observed， protein and mRNA expressions of p53， ULK1， Beclin-1 and microtubule-associated protein 1 light chain 3 （LC3）， and expression of miR-214 in renal tissue were also determined. RESULTS Compared with the normal group， the renal tubular epithelium of rats in the model group showed obvious edema， cell swelling， accompanied by lymphocyte infiltration； the levels of 24h-UTP， BUN， SCr， ALT and glycolipid indexes， the expressions of p53 protein and mRNA， as well as the expression of miR-214 in rats in the model group and administration groups were significantly increased or up-regulated， while ALB level， LC3-Ⅱ/LC3-Ⅰ， the expressions of LC3 mRNA， the expressions of ULK1， Beclin-1 protein and mRNA were significantly decreased or down-regulated （P＜0.01）. Compared with the model group， the histopathological damage of the kidney in rats was improved in administration groups； the levels of 24 h-UTP， BUN， SCr， ALT and glycolipid indexes， the expressions of p53 protein and mRNA， as well as the expression of miR-214 were all significantly decreased or down-regulated， while ALB level， LC3-Ⅱ/LC3-Ⅰ， the expressions of LC3 mRNA， the expressions of ULK1 and Beclin-1 protein and mRNA were significantly increased or up-regulated （P＜0.01）. CONCLUSIONS TG can alleviate renal damage in DN rats， and improve their liver and renal function， as well as glucose and lipid levels. These effects may be related to the regulation of the p53/miR-214/ULK1 axis and the restoration of cellular autophagy.

ObjectiveAccording to the theory of medicinal properties in traditional Chinese medicine （TCM）， Tangye Jingfa Tu， implying that all tonic prescriptions should primarily feature sweetness. However， the "Chart of the Classic Methods of Decoction Therapy" recorded in Mnemonic Aids for Medical Practice （Fuxingjue） proposes that each of the Zangfu organs has a corresponding tonifying flavor， i.e.， pungent for the liver， salty for the heart， sweet for the spleen， sour for the lungs， and bitter for the kidneys. Therefore， deficiency syndromes of different organs should be primarily addressed with specific medicinal flavors. This study applies this theoretical framework to analyze the formulation and compatibility principles and efficacy positioning of commonly used TCM tonic prescriptions， providing a reference for differentiated clinical medication. MethodsA database of tonic prescriptions was established based on the textbook Science of Prescriptions. Excel software was used to separately calculate the number of medicinal types， frequency of use， flavors， and proportional composition of the prescriptions. The prescriptions were categorized to determine their compatibility structures and functional characteristics. ResultsA total of 60 prescriptions were included， classified into six categories， involving 110 medicinal types with 469 instances of use. From the perspective of the "Chart of the Classic Methods of Decoction Therapy"， different tonic prescriptions exhibit distinct dominant medicinal flavors and organ associations. Specifically， 15 Qi-tonifying prescriptions primarily adopted a "sweet flavor" to tonify the spleen. Nine blood-tonifying prescriptions primarily adopted a "pungent-salty flavor" to tonify the liver and heart. Seven Qi-and-blood-tonifying prescriptions primarily featured a "sweet-pungent flavor" to tonify the spleen and liver. Nineteen Yin-tonifying prescriptions primarily adopted a "bitter-sour flavor" to tonify the kidneys and lungs. Seven Yang-tonifying prescriptions primarily featured a "pungent-bitter flavor" to tonify the liver and kidneys. Three Yin-and-Yang-tonifying prescriptions primarily featured a "bitter-pungent-sweet flavor" to tonify the kidneys， liver， and spleen. ConclusionThe "Chart of the Classic Methods of Decoction Therapy" clearly illustrates the formulation and compatibility principles and key differences among various tonic prescriptions， indicating that not all tonic prescriptions are predominantly sweet in flavor. This provides new insights for the clinical modification and application of tonic prescriptions.

ObjectiveAccording to the theory of medicinal properties in traditional Chinese medicine （TCM）， Tangye Jingfa Tu， implying that all tonic prescriptions should primarily feature sweetness. However， the "Chart of the Classic Methods of Decoction Therapy" recorded in Mnemonic Aids for Medical Practice （Fuxingjue） proposes that each of the Zangfu organs has a corresponding tonifying flavor， i.e.， pungent for the liver， salty for the heart， sweet for the spleen， sour for the lungs， and bitter for the kidneys. Therefore， deficiency syndromes of different organs should be primarily addressed with specific medicinal flavors. This study applies this theoretical framework to analyze the formulation and compatibility principles and efficacy positioning of commonly used TCM tonic prescriptions， providing a reference for differentiated clinical medication. MethodsA database of tonic prescriptions was established based on the textbook Science of Prescriptions. Excel software was used to separately calculate the number of medicinal types， frequency of use， flavors， and proportional composition of the prescriptions. The prescriptions were categorized to determine their compatibility structures and functional characteristics. ResultsA total of 60 prescriptions were included， classified into six categories， involving 110 medicinal types with 469 instances of use. From the perspective of the "Chart of the Classic Methods of Decoction Therapy"， different tonic prescriptions exhibit distinct dominant medicinal flavors and organ associations. Specifically， 15 Qi-tonifying prescriptions primarily adopted a "sweet flavor" to tonify the spleen. Nine blood-tonifying prescriptions primarily adopted a "pungent-salty flavor" to tonify the liver and heart. Seven Qi-and-blood-tonifying prescriptions primarily featured a "sweet-pungent flavor" to tonify the spleen and liver. Nineteen Yin-tonifying prescriptions primarily adopted a "bitter-sour flavor" to tonify the kidneys and lungs. Seven Yang-tonifying prescriptions primarily featured a "pungent-bitter flavor" to tonify the liver and kidneys. Three Yin-and-Yang-tonifying prescriptions primarily featured a "bitter-pungent-sweet flavor" to tonify the kidneys， liver， and spleen. ConclusionThe "Chart of the Classic Methods of Decoction Therapy" clearly illustrates the formulation and compatibility principles and key differences among various tonic prescriptions， indicating that not all tonic prescriptions are predominantly sweet in flavor. This provides new insights for the clinical modification and application of tonic prescriptions.

OBJECTIVE To investigate the effectiveness of resident clinical pharmacist-led medication therapy management （MTM） model in geriatric cardiology departments， and provide reference for optimizing resident pharmaceutical services. METHODS A retrospective cohort study was conducted， incorporating data from inpatients admitted to the Department of Cardiovascular Medicine in the Geriatric Medical Center of our hospital during March to August 2023 （conventional group， n＝ 903） and the same period in 2024 （MTM group， n＝963）. The conventional group received only standard pharmaceutical services （including prospective prescription review and retrospective order evaluation）， while the MTM group received additional resident clinical pharmacist-led interventions-such as medication reconciliation， personalized therapeutic drug monitoring （TDM）， standardized intravenous infusion management， and a four-stage closed-loop monitoring process-based on conventional care. The effectiveness of the MTM model was evaluated by comparing the primary outcome measures （e.g.， intravenous infusion rate， TDM target attainment rate） and secondary outcome measures [e.g.， incidence of drug-drug interactions （DDIs）， incidence of grade 3 or higher acute kidney injury， average length of hospital stay， cholesterol， and medication cost per capita] between the two groups. RESULTS Compared with the conventional group， in terms of primary outcome indexes： both the overall intravenous infusion rate and the use rate of acid-suppressive injection were significantly lowered in the MTM group （P＜0.05）； serum concentration target attainment rates for digoxin and vancomycin were increased significantly （P＜0.05）. For secondary outcome indexes， the MTM group exhibited significant decreases in the work incidence of grade 3 or higher acute kidney injury， the incidence of DDIs， the rate of patients leaving the hospital against medical advice， alanine amino-transferase， aspartate transferase and the per capita total medication cost （P＜0.05）. Additionally， there was a notable increase in the creatinine， estimated glomerular filtration rate and a significant shortening of the per capita length of hospital stay （P＜0.05）. CONCLUSIONS The resident clinical pharmacist-led MTM model can significantly optimize medication therapy processes， enhance medication safety and cost-effectiveness， thus playing a positive role in promoting rational drug use and improving patient outcomes.

Recent studies have shown that an imbalance in iron metabolism can affect the composition and microstructural changes of bone, disrupting bone homeostasis and leading to osteoporosis(OP). The imbalance in iron metabolism, along with its induced local abnormal microenvironment and cellular iron death, has become a new focal point in OP research, drawing increasing attention from the academic community regarding the regulation of iron metabolism to prevent and manage OP. From the perspective of traditional Chinese medicine(TCM), iron metabolism imbalance has potential connections to TCM theories regarding internal organs, as well as treatments aimed at tonifying the kidney, strengthening the spleen, and activating blood circulation. Evidence is continually emerging that TCMs and effective components that tonify the kidney, strengthen the spleen, and activate blood circulation can prevent and manage OP by regulating iron metabolism. This article analyzes the relationship between iron and bone, as well as the effects of TCM formulations on improving iron metabolism and influencing bone metabolism, from the perspectives of iron metabolism mechanisms and TCM interventions, aiming to broaden existing clinical strategies for prevention and treatment and inject new momentum into the field of OP as it moves into a new era.
Osteoporosis/drug therapy* ; Humans ; Iron/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Medicine, Chinese Traditional ; Bone and Bones/drug effects*

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

OBJECTIVE: To identify prognostic genes associated with lysosome-dependent cell death (LDCD) in patients with gastric cancer (GC). METHODS: Differentially expressed genes (DEGs) were identified using The Cancer Genome Atlas - Stomach Adenocarcinoma. Weighted gene co-expression network analysis was performed to identify the key module genes associated with LDCD score. Candidate genes were identified by DEGs and key module genes. Univariate Cox regression analysis, and least absolute shrinkage and selection operator regression and multivariate Cox regression analyses were performed for the selection of prognostic genes, and risk module was established. Subsequently, key cells were identified in the single-cell dataset (GSE183904), and prognostic gene expression was analyzed. Cell proliferation and migration were assessed using the Cell Counting Kit-8 assay and the wound healing assay. RESULTS: A total of 4,465 DEGs, 95 candidate genes, and 4 prognostic genes, including C19orf59, BATF2, TNFAIP2, and TNFSF18, were identified in the analysis. Receiver operating characteristic curves indicated the excellent predictive power of the risk model. Three key cell types (B cells, chief cells, and endothelial/pericyte cells) were identified in the GSE183904 dataset. C19orf59 and TNFAIP2 exhibited predominant expression in macrophage species, whereas TNFAIP2 evolved over time in endothelial/pericyte cells and chief cells. Functional experiments confirmed that interfering with C19orf59 inhibited proliferation and migration in GC cells. CONCLUSION C19orf59, BATF2, TNFAIP2, and TNFSF18 are prognostic genes associated with LDCD in GC. Furthermore, the risk model established in this study showed robust predictive power.
Stomach Neoplasms/pathology* ; Humans ; Prognosis ; Lysosomes/physiology* ; RNA-Seq ; Cell Death ; Single-Cell Analysis ; Gene Expression Regulation, Neoplastic ; Cell Proliferation ; Single-Cell Gene Expression Analysis

Heart failure with preserved ejection fraction (HFpEF) accounts for about half of the number of patients with heart failure. In addition to the typical features of heart failure such as myocardial stiffness and diastolic function impairment, the key characteristic of HFpEF is the normal left ventricular ejection fraction, which increases the difficulty of clinical diagnosis. QiShenYiQi Dripping Pills (QSYQ) is a standardized traditional Chinese medicine approved by the China Food and Drug Administration (CFDA), and many clinical studies have demonstrated the efficacy and safety of QSYQ in the treatment of heart failure with reduced ejection fraction, but the role of QSYQ in HFpEF has not been clarified. In this paper, high fat diet (HFD) and drinking water containing N-nitro-L-arginine methyl ester (L-NAME, 0.5 g·L^-1, pH=7.4) were used in C57BL/6N male mice to construct the classical HFpEF model (the experiment was approved by the Animal Ethics Committee of Hefei University of Technology, the approval number is HFUT20220921002), and at the 8^th week, the mice were dosed with ① empagliflozin, ② low-dose QSYQ (LQ), ③ high-dose QSYQ (HQ), ④ empagliflozin plus low-dose QSYQ (ELQ) for 4 weeks, the body weight of the mice was recorded during the experiment, echocardiography, blood pressure and glucose tolerance were detected and the exercise capacity of mice was evaluated, and pathological and biochemical experiments were used to detect cardiac fibrosis, liver fibrosis and serum biochemical indexes in mice, RNAseq assay was performed with mice heart tissues. The results showed that QSYQ as well as QSYQ+empagliflozin could significantly reduce the body weight, improve diastolic function and hypertension, improve glucose tolerance and enhance exercise ability of HFpEF mice. At the biochemical and molecular levels, QSYQ and QSYQ+empagliflozin can reduce the cross-sectional area of cardiomyocytes and reduce cardiac collagen contents, thereby alleviating myocardial hypertrophy and fibrotic phenotypes, and improve metabolic disorders. The RNAseq results suggest that the function of QSYQ in improving HFpEF may be related to calsequestrin 1. In conclusion, this study shows that QSYQ and QSYQ+empagliflozin can significantly improve HFpEF-related cardiac dysfunction and metabolic disorders, which provides a theoretical basis for the clinical treatment of HFpEF.