1.Research Tackling Paradigm and Technological Layout Strategies Based on Erectile Dysfunction, A Clinical Dominant Disease of Traditional Chinese Medicine
Qi ZHAO ; Yun CHEN ; Baoxing LIU ; Xuejun SHANG ; Fei SUN ; Xiaozhi ZHAO ; Zhigang WU ; Chao SUN ; Peihai ZHANG ; Wanjun CHENG ; Xing ZHOU ; Zhan QIN ; Yufeng PAN ; Weiwei TAO ; Jianhuai CHEN ; Mei MO ; Xiaoxiao ZHANG ; Xing ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):291-299
To thoroughly implement the strategic deployment outlined in the Opinions of the Central Committee of the Communist Party of China and the State Council on Promoting the Inheritance and Innovative Development of Traditional Chinese Medicine regarding research on dominant diseases of traditional Chinese medicine and to uphold the development philosophy of equal emphasis on traditional Chinese medicine and western medicine,the China Association of Chinese Medicine has fully played a leading academic role by systematically organizing and conducting a series of academic youth salons on clinical dominant diseases of traditional Chinese medicine. On September 13,2024,the 36th Youth Salon on Clinical Dominant Diseases was successfully held in Nanjing,focusing on the advantages of traditional Chinese medicine and the integrative traditional Chinese medicine and western medicine in the diagnosis and treatment of erectile dysfunction (ED). The conference brought together leading experts from traditional Chinese medicine,western medicine,and interdisciplinary fields,facilitating in-depth multidisciplinary discussions that led to key consensus on optimizing traditional Chinese medicine treatment protocols for ED,researching and developing new drugs of traditional Chinese medicine,and advancing interdisciplinary development in traditional Chinese medicine. This salon systematically sorted out the clinical strengths and distinctive features of traditional Chinese medicine in the diagnosis and treatment of ED. Based on current research foundations and clinical needs,it identified key directions for future scientific layout and scientific research tackling: (1) Standardization of syndrome differentiation system of traditional Chinese medicine for ED. (2) Optimization and standardization of intervention methods of integrated traditional Chinese medicine and western medicine. (3) High-quality clinical research guided by evidence-based medicine. (4) In-depth analysis of the pharmacological mechanisms of traditional Chinese medicine in the treatment of ED. (5) Clinical translation and application promotion of new drugs of traditional Chinese medicine. (6) Interdisciplinary integration and innovation in traditional Chinese medicine. For each research direction,key focus areas,expected objectives,and clinical value were further refined,along with the establishment of a scientifically sound priority funding level evaluation system. Therefore,building on the series of salons on the ED-focused dominant diseases of traditional Chinese medicine,this paper provides standardized guidance for clinical practice of traditional Chinese medicine in ED management,effectively contributing to the high-quality development of traditional Chinese medicine. It serves as a valuable reference for national scientific and technological strategic layout, research and development decision-making in new drugs of traditional Chinese medicine,research topic planning,and clinical guideline formulation.
2.Mechanism of the interaction between immunosuppressive therapy and intestinal microflora after liver transplantation
Yan WANG ; Yufeng LIU ; Haiyang ZHANG ; Zhiwei ZHANG ; Jun XU ; Zhiyong LAI
Journal of Clinical Hepatology 2026;42(4):980-986
The application of immunosuppressants has significantly reduced the incidence rate of rejection reaction after liver transplantation, but the clinical efficacy of immunosuppressants is greatly affected by individual differences between patients. This article systematically reviews the recent research advances in the interaction between immunosuppressants and gut microbiota, with a focus on the regulatory role and mechanism of intestinal microflora communities on the efficacy of immunosuppressants. Studies have shown that intestinal microbiome is one of the key factors influencing the efficacy of immunosuppressive therapy after liver transplantation. This review aims to provide a theoretical basis for in-depth research in this field and provide new insights for developing individualized immunosuppressive treatment regimens based on the regulation of intestinal microflora.
3.Mechanism Investigation of Qi-invigorating and Blood-activating Drug Combination in Yitangkang Compound Against Diabetic Cardiomyopathy Using Multimodal Research Approach
Chenghao YU ; Tingting LI ; Mingbo ZHANG ; Honghe XIAO ; Yufeng YANG ; Yan SHI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(24):94-106
ObjectiveThrough multimodal research methods including medication rule mining, network pharmacology, molecular docking and dynamics simulation, and in vivo animal experiments, this study aims to speculate and verify the core composition (Ginseng Radix et Rhizoma Rubra-Salviae Miltiorrhizae Radix et Rhizoma-Notoginseng Radix et Rhizoma) and efficacy (Qi-invigorating and blood-activating) of the drug combination in Yitangkang Compound for improving diabetic cardiomyopathy (DCM), investigate the interaction relationship and binding strength between core active ingredients of the drug combination and key signaling pathway targets, and further explore the mechanism by which the Qi-invigorating and blood-activating drug combination regulates the calcium signaling pathway to improve cardiac function in DCM rats. MethodsThe Ancient and Modern Medical Cases Cloud Platform was used to construct a DCM prescription database, and the "Analysis Method" module of the platform was applied to mine and summarize medication rules, thereby determining the core composition of the Qi-invigorating and blood-activating drug combination in Yitangkang. Drug-active ingredient-signaling pathway-core target-disease analysis and visualization were conducted by combining network pharmacology with the Traditional Chinese Medicine System Pharmacology Platform (TCMSP) database, SwissTargetPrediction platform, GeneCards database, MetaScape database, CytoScape software, etc. Then, molecular docking was performed via the CB-Dock2 platform, and molecular dynamics simulation of the high-binding-strength docking complexes was carried out by Gromacs software. Finally, in vivo animal experiments were carried out. Twenty-eight Sprague Dawley (SD) rats meeting the research criteria were divided into a normal group, a model group, a drug combination group (3.3 g·kg-1), and a Yitangkang group (20 g·kg-1). A type 2 diabetes mellitus (T2DM) rat model was established by high-fat diet feeding combined with intraperitoneal injection of streptozotocin (STZ), followed by continuous feeding for eight weeks until the DCM model was successfully established. During this period, the traditional Chinese medicine (TCM) compound and drug combination were administered for prevention and treatment intervention. Meanwhile, changes in blood glucose, body weight, and heart index of each group were monitored. Cardiac function was assessed by echocardiography, and electrophysiological signals were detected by an electrocardiogram. The heart tissue was observed for pathological changes by hematoxylin-eosin (HE) and Masson staining, and the expression of L-type calcium channel (CACNA1C), calmodulin (CALM1), calcium/calmodulin-dependent protein kinase Ⅱδ (CAMK2D), and neuronal nitric oxide synthase (NOS1) proteins in the calcium signaling pathway of myocardial tissue was detected by Western blot. ResultsIn 62 DCM prescriptions, Ginseng Radix et Rhizoma Rubra, Salviae Miltiorrhizae Radix et Rhizoma, and Notoginseng Radix et Rhizoma were used most frequently. Their meridian tropism mainly involved the spleen, heart, and lung, and their sweet and warm properties were prominent. The drugs for tonifying or blood-activating and stasis-resolving ranked top. In association rule analysis, (Ginseng Radix et Rhizoma Rubra, Salviae Miltiorrhizae Radix et Rhizoma)-Notoginseng Radix et Rhizoma had the highest lift. Network pharmacology obtained 75 active ingredients of the drug combination, 714 drug combination action targets, 2 702 disease targets, and 286 intersection targets. Protein-protein interaction (PPI) network predicted nine interaction component-targets (nine active ingredients and four calcium signaling pathway target genes). Molecular docking showed the four complexes with the lowest binding energy were 2f3z-ginsenoside Re, 1cll-quercetin, 9blh-(6S)-6-(hydroxymethyl)-1,6-dimethyl-8,9-dihydro-7H-naphtho[8,7-g]benzofuran-10,11-dione, and 5vv0-miltionone Ⅱ. Dynamics simulation showed the CALM1-quercetin complex had the strongest binding affinity. The animal experiment results revealed that compared with the normal group, the model group showed significant changes in blood glucose, body weight, myocardial tissue morphology, heart index, cardiac function, electrophysiological indexes, and the expression levels of CACNA1C, CALM1, CAMK2D, and NOS1 proteins (P<0.05, P<0.01). Compared with the model group, the Yitangkang group had a certain improvement effect on the above indexes (P<0.05, P<0.01). Compared with the Yitangkang group, the drug combination group showed no significant difference in improving myocardial tissue morphology, heart index, cardiac function, electrophysiological indexes, and the expression of CACNA1C, CALM1, CAMK2D, and NOS1 proteins, except for blood glucose and body weight. ConclusionGinseng Radix et Rhizoma Rubra, Salviae Miltiorrhizae Radix et Rhizoma, and Notoginseng Radix et Rhizoma are the core Qi-invigorating and blood-activating drug combination in Yitangkang Compound. They have a good preventive and therapeutic effect on STZ-induced DCM in rats, and their mechanism of action may be related to the regulation of the calcium signaling pathway.
4.Chinese agarwood petroleum ether extract suppressed gastric cancer progression via up-regulation of DNA damage-induced G0/G1 phase arrest and HO-1-mediated ferroptosis.
Lishan OUYANG ; Xuejiao WEI ; Fei WANG ; Huiming HUANG ; Xinyu QIU ; Zhuguo WANG ; Peng TAN ; Yufeng GAO ; Ruoxin ZHANG ; Jun LI ; Zhongdong HU
Chinese Journal of Natural Medicines (English Ed.) 2025;23(10):1210-1220
Gastric cancer (GC) is characterized by high morbidity and mortality rates. Chinese agarwood comprises the resin-containing wood of Aquilaria sinensis (Lour.) Gilg., traditionally utilized for treating asthma, cardiac ischemia, and tumors. However, comprehensive research regarding its anti-GC effects and underlying mechanisms remains limited. In this study, Chinese agarwood petroleum ether extract (CAPEE) demonstrated potent cytotoxicity against human GC cells, with half maximal inhibitory concentration (IC50) values for AGS, HGC27, and MGC803 cells of 2.89, 2.46, and 2.37 μg·mL-1, respectively, at 48 h. CAPEE significantly induced apoptosis in these GC cells, with B-cell lymphoma-2 (BCL-2) associated X protein (BAX)/BCL-2 antagonist killer 1 (BAK) likely mediating CAPEE-induced apoptosis. Furthermore, CAPEE induced G0/G1 phase cell cycle arrest in human GC cells via activation of the deoxyribonucleic acid (DNA) damage-p21-cyclin D1/cyclin-dependent kinase 4 (CDK4) signaling axis, and increased Fe2+, lipid peroxides and reactive oxygen species (ROS) levels, thereby inducing ferroptosis. Ribonucleic acid (RNA) sequencing, real-time quantitative polymerase chain reaction (RT-qPCR), and Western blotting analyses revealed CAPEE-mediated upregulation of heme oxygenase-1 (HO-1) in human GC cells. RNA interference studies demonstrated that HO-1 knockdown reduced CAPEE sensitivity and inhibited CAPEE-induced ferroptosis in human GC cells. Additionally, CAPEE administration exhibited robust in vivo anti-GC activity without significant toxicity in nude mice while inhibiting tumor cell growth and promoting apoptosis in tumor tissues. These findings indicate that CAPEE suppresses human GC cell growth through upregulation of the DNA damage-p21-cyclin D1/CDK4 signaling axis and HO-1-mediated ferroptosis, suggesting its potential as a candidate drug for GC treatment.
Animals
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Humans
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Mice
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Antineoplastic Agents, Phytogenic
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Apoptosis/drug effects*
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Cell Line, Tumor
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Cyclin D1/genetics*
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Cyclin-Dependent Kinase 4/genetics*
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DNA Damage/drug effects*
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Drugs, Chinese Herbal/pharmacology*
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Ferroptosis/drug effects*
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G1 Phase Cell Cycle Checkpoints/drug effects*
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Heme Oxygenase-1/genetics*
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Mice, Inbred BALB C
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Mice, Nude
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Plant Extracts/pharmacology*
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Stomach Neoplasms/physiopathology*
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Thymelaeaceae/chemistry*
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Up-Regulation/drug effects*
5.Clinical efficacy of a novel autologous blood recovery device during ECMO weaning
Yufeng LU ; Chuanfa ZHANG ; Dongmei FAN ; Shuo HU ; Xianming WEN ; Ziyou LIU
Chinese Journal of Blood Transfusion 2025;38(11):1573-1576
Objective: To evaluate the clinical efficacy of a novel autologous blood recovery device during the weaning process from extracorporeal membrane oxygenation (ECMO). Methods: A total of 16 patients who received ECMO support and underwent blood recovery during the weaning process from January 2022 to September 2024 at our hospital were included in the experimental group. In contrast, 58 patients who did not receive blood recovery during the weaning process were assigned to the control group. Transfusion components, costs, and changes in routine blood tests and coagulation functions were compared between the two groups from the day of weaning until 48 hours post-weaning. Results: Significant differences were observed in the volumes of red blood cell transfusions, plasma transfusions, and transfusion costs between the two groups from the day of weaning to 48 hours post-weaning (P<0.05). Additionally, in the experimental group, significant differences were noted in hemoglobin (Hb), platelet (Plt), and activated partial thromboplastin time (APTT) results when comparing values before and after extubation (P<0.05). Conclusion: The application of a novel autologous blood recovery device during ECMO weaning reduces patient costs, minimizes wastage of autologous blood, decreases reliance on exogenous blood transfusions, and mitigates the risks associated with allogeneic blood transfusion. This approach merits further promotion for clinical use.
6.Best evidence summary for preventing and managing post-transplant diabetes mellitus in lung transplant patients
Yao HUANG ; Lihua CHEN ; Qingqing SHENG ; Xinning WANG ; Tingting HE ; Yufeng TAN ; Shuqin ZHANG
Chongqing Medicine 2025;54(7):1667-1672,1678
Objective To retrieve,analyze and synthesize evidence on post-transplant diabetes mellitus(PTDM)in lung transplant patients,providing reference for clinical healthcare professionals in preventing and managing PTDM in lung transplant patients.Methods Based on the"6S"evidence model,systematic searches were conducted across guideline websites,professional associations,and Chinese/English databases regarding post-transplant diabetes mellitus(PTDM)in lung transplant patients.The search period spanned from data-base inception to January 2025.Two researchers independently completed literature screening,quality assess-ment,and evidence extraction.Results A total of 14 articles were included,comprising 1 clinical decision,2 guidelines,5 expert consensuses,2 specifications,1 evidence summary,and 3 systematic reviews.Twenty-four pieces of best evidence were synthesized from seven aspects:risk factors,diagnosis,screening,prevention,treatment,glycemic control targets,and health education.Conclusion The best evidence for preventing and managing post-transplant diabetes mellitus in lung transplant patients provides an evidence-based foundation for clinical practice among healthcare professionals.Evidence should be selected and applied according to spe-cific clinical situations and patient needs.
7.Facilitation of mucosal healing by estrogen receptor β in ulcerative colitis through suppression of branched-chain amino acid transport and subsequent triggering of autophagy in colonic epithelial cells.
Yilei GUO ; Yanrong ZHU ; Jing ZHANG ; Yue HE ; Mianjiang ZHAO ; Haochang LIN ; Zhifeng WEI ; Yufeng XIA ; Yue DAI
Acta Pharmaceutica Sinica B 2025;15(1):168-187
Colonic mucosal healing is the ultimate goal of ulcerative colitis (UC) treatment, but it remains difficult to realize. Given the higher incidence of UC in males and the beneficial effect of estrogen on UC, we conducted this study to examine the therapeutic potential of estrogen receptor β (ERβ), the primary ER subtype in colon, on mucosal healing in UC. Our study is the first to report that ERβ activation degree was positively correlated with mucosal healing in patients with UC. Furthermore, ERβ activation enhanced mucosal healing in mice with dextran sulfate sodium-induced and biopsy-induced colonic injuries. Mechanistically, ERβ activation promoted autophagy of colonic epithelial cells by inhibiting branched-chain amino acid transport, leading to focal adhesion kinase (FAK) activation. Activated FAK promoted focal adhesion turnover and colonic epithelial cell migration, ultimately facilitating mucosal healing. ERβ -/- colitis mice exhibited impaired mucosal healing compared to wild-type littermates, highlighting the crucial effect of ERβ. Importantly, combination with ERβ-agonist diarylpropionitrile enhanced the amelioration of 5-aminosalicylic acid, a standard UC treatment agent, against mouse colitis. These findings attest to the crucial role of ERβ activation in colonic mucosal healing and may further inform the development of novel strategies for UC treatment.
8.Diabetes-associated sleep fragmentation impairs liver and heart function via SIRT1-dependent epigenetic modulation of NADPH oxidase 4.
Yuanfang GUO ; Jie WANG ; Dongmei ZHANG ; Yufeng TANG ; Quanli CHENG ; Jiahao LI ; Ting GAO ; Xiaohui ZHANG ; Guangping LU ; Mingrui LIU ; Xun GUAN ; Xinyu TANG ; Junlian GU
Acta Pharmaceutica Sinica B 2025;15(3):1480-1496
Although clinical evidence suggests that nonalcoholic fatty liver disease is an established major risk factor for heart failure, it remains unexplored whether sleep disorder-caused hepatic damage contributes to the development of cardiovascular disease (CVD). Here, our findings revealed that sleep fragmentation (SF) displayed notable hepatic detrimental phenotypes, including steatosis and oxidative damage, along with significant abnormalities in cardiac structure and function. All these pathological changes persisted even after sleep recovery for 2 consecutive weeks or more, displaying memory properties. Mechanistically, persistent higher expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) in the liver was the key initiator of SF-accelerated damage phenotypes. SF epigenetically controlled the acetylation of histone H3 lysine 27 (H3K27ac) enrichment at the Nox4 promoter and markedly increased Nox4 expression in liver even after sleep recovery. Moreover, fine coordination of the circadian clock and hepatic damage was strictly controlled by BMAL1-dependent Sirtuin 1 (Sirt1) transcription after circadian misalignment. Accordingly, genetic manipulation of liver-specific Nox4 or Sirt1, along with pharmacological intervention targeting NOX4 (GLX351322) or SIRT1 (Resveratrol), could effectively erase the epigenetic modification of Nox4 by reducing the H3K27ac level and ameliorate the progression of liver pathology, thereby counteracting SF-evoked sustained CVD. Collectively, our findings may pave the way for strategies to mitigate myocardial injury from persistent hepatic detrimental memory in diabetic patients.
9.Melatonin receptor 1a alleviates sleep fragmentation-aggravated testicular injury in T2DM by suppression of TAB1/TAK1 complex through FGFR1.
Xiaohui ZHANG ; Xinyu TANG ; Ting GAO ; Yuanfang GUO ; Guangping LU ; Qingbo LIU ; Jiahao LI ; Jie WANG ; Mingrui LIU ; Dongmei ZHANG ; Yufeng TANG ; Junlian GU
Acta Pharmaceutica Sinica B 2025;15(7):3591-3610
A major obstacle in type 2 diabetes mellitus (T2DM) is sleep fragmentation (SF), which negatively affects testicular function. However, the underlying mechanisms remain to be elucidated. In this study, we demonstrate that SF induces testicular damage through a mechanism involving lipid metabolism, specifically mediated by melatonin (MEL) receptor 1a (MT1). T2DM mice with SF intervention displayed several deleterious phenotypes such as apoptosis, deregulated lipid metabolism, and impaired testicular function. Unexpectedly, sleep recovery (SR) for 2 consecutive weeks could not completely abrogate SF's detrimental effects on lipid deposition and testicular function. Interestingly, MEL and MT1 agonist 2-iodomelatonin (2IM) effectively improved lipid homeostasis, highlighting MEL/2IM as a promising therapeutic drug for SF-trigged testicular damage. Mechanistically, MEL and 2IM activated FGFR1 and sequentially restrained the crosstalk and physical interaction between TAB1 and TAK1, which ultimately suppressed the phosphorylation of TAK1 to block lipid deposition and cell apoptosis caused by SF. The ameliorating effect of MEL/2IM was overtly nullified in Fgfr1 knockout (Fgfr1-KO +/- ) diabetic mice. Meanwhile, testicular-specific overexpression of Tak1 abolished the protective effect of FGF1mut on diabetic mouse testis. Our findings offer valuable insights into the molecular mechanisms underlying the testicular pathogenesis associated with SF and propose a novel therapeutic approach for addressing male infertility in T2DM.
10.AI-integrated IQPD framework of quality prediction and diagnostics in small-sample multi-unit pharmaceutical manufacturing: Advancing from experience-driven to data-driven manufacturing.
Kaiyi WANG ; Xinhai CHEN ; Nan LI ; Huimin FENG ; Xiaoyi LIU ; Yifei WANG ; Yanfei WU ; Yufeng GUO ; Shuoshuo XU ; Lu YAO ; Zhaohua ZHANG ; Jun JIA ; Zhishu TANG ; Zhisheng WU
Acta Pharmaceutica Sinica B 2025;15(8):4193-4209
The pharmaceutical industry faces challenges in quality digitization for complex multi-stage processes, especially in small-sample systems. Here, an intelligent quality prediction and diagnostic (IQPD) framework was developed and applied to Tong Ren Tang's Niuhuang Qingxin Pills, utilizing four years of data collected from four production units, covering the entire process from raw materials to finished products. In this framework, a novel path-enhanced double ensemble quality prediction model (PeDGAT) is proposed, which combines a graph attention network and path information to encode inter-unit long-range and sequential dependencies. Additionally, the double ensemble strategy enhances model stability in small samples. Compared to global traditional models, PeDGAT achieves state-of-the-art results, with an average improvement of 13.18% and 87.67% in prediction accuracy and stability on three indicators. Additionally, a more in-depth diagnostic model leveraging grey correlation analysis and expert knowledge reduces reliance on large samples, offering a panoramic view of attribute relationships across units and improving process transparency. Finally, the IQPD framework integrates into a Human-Cyber-Physical system, enabling faster decision-making and real-time quality adjustments for Tong Ren Tang's Niuhuang Qingxin Pills, a product with annual sales exceeding 100 million CNY. This facilitates the transition from experience-driven to data-driven manufacturing.

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