1.Research progress in small molecule inhibitors of complement factor B
Shuai WEN ; Yao ZHAO ; Yan WANG ; Xing LI ; Yi MOU ; Zheng-yu JIANG
Acta Pharmaceutica Sinica 2025;60(1):37-47
The alternative pathway (AP) of the complement system is a key contributor to the pathogenesis of several diseases including paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), C3 glomerular disease (C3G) and age-related macular degeneration (AMD). Complement factor B (CFB) is a trypsin-like serine protein that circulates in the human bloodstream in a latent form. As a key node of the alternative pathway, it is an important target for the treatment of diseases mediated by the complement system. With the successful launch of iptacopan, the CFB small molecule inhibitors has become a current research hotspot, a number of domestic and foreign pharmaceutical companies are actively developing CFB small molecule inhibitors. In this paper, the research progress of CFB small molecule inhibitors in recent years is systematically summarized, the representative compounds and their activities are introduced according to structural types and design ideas, so as to provide reference and ideas for the subsequent research on CFB small molecule inhibitors.
2.Establishment and application of a precise management model for the centralized preparation of cytotoxic drugs in PIVAS
Shuai LIU ; Daiyi LI ; Jinhuan SU ; Shangjun GU ; Ningbo MOU ; Yunli ZHOU ; Yan LAI
China Pharmacy 2025;36(19):2437-2441
OBJECTIVE To establish the precise management model for the centralized preparation of cytotoxic drugs in pharmacy intravenous admixture services (PIVAS), and evaluate the effects of its application. METHODS Pharmacists in PIVAS established the precise management model by soliciting clinical opinions and consulting literature on the centralized preparation of cytotoxic drugs and continuously refining every step of the preparation of cytotoxic drugs, based on data feedback from the information closed-loop management system and the limit of stability time of finished solutions. The indicators such as the preparation time, delivery time, the storage time of finished infusion solutions after preparation, and the completion rate of infusion within the stability time limit were analyzed before the implementation (January to December 2023) and after the implementation (January to December 2024) of this model, to evaluate its application effectiveness. RESULTS The overall framework for the precise management model included upgrading the functions of the prescription review system, improving the prescription review database, providing specialized training for PIVAS pharmacists, managing dynamic batch decision for drug preparation, managing special drugs, managing finished infusion distribution, and establishing a continuous improvement mechanism. Compared with before implementation, the average preparation time of the second and third batches of cytotoxic drugs with more concentrated morning preparation tasks in this model was significantly shorter than before implementation (P<0.05); the delivery time of finished infusion after implementation ([ 11.49±2.92) min] was significantly shorter than the delivery time before implementation ([ 22.11±5.03) min] (P<0.001); the storage time of some drugs with shorter stable time limit and carboplatin in combination regimens (paclitaxel or docetaxel+carboplatin) was significantly shortened compared to before implementation (P<0.05), and the completion rate of infusion within the stability time limit was significantly improved compared to before implementation (P<0.05). CONCLUSIONS Our hospital has successfully established a precise management model for the centralized preparation of cytotoxic drugs in PIVAS. This mode can significantly shorten the preparation time of each batch of PIVAS in the morning, make batch decisions more reasonable and improve the infusion completion rate within the stable time limit of the finished product.
3.Herbal Textual Research on Tribuli Fructus and Astragali Complanati Semen in Famous Classical Formulas
Jiaqin MOU ; Wenjing LI ; Yanzhu MA ; Yue ZHOU ; Wenfeng YAN ; Shijun YANG ; Ling JIN ; Jing SHAO ; Zhijia CUI ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(22):241-251
By systematically combing ancient and modern literature, this paper examined Tribuli Fructus and Astragali Complanati Semen(ACS) used in the famous classical formulas from the aspects of name, origin, production area, harvesting and processing, clinical efficacy, so as to provide a basis for the development of famous classical formulas containing such medicinal materials. The results showed that the names of Tribuli Fructus in the past dynasties were mostly derived from its morphology, and there were nicknames such as Baijili, Cijili and Dujili. The name of ACS in the past dynasties were mostly originated from its production areas, and there were nicknames such as Baijili, Shayuan Jili and Tongjili. Because both of them had the name of Baijili, confusion began to appear in the Song dynasty. In ancient and modern times, the main origin of Tribuli Fructus were Tribulus terrestris, and ancient literature recorded the genuine producing areas of Tribuli Fructus was Dali in Shaanxi and Tianshui in Gansu, but today it is mainly cultivated in Anhui and Shandong. The fruit is the medicinal part, harvested in autumn throughout history. There is no description of the quality of Tribuli Fructus in ancient times, and the plump, firm texture, grayish-white color is the best in modern times. Traditional processing methods for Tribuli Fructus included stir-frying and wine processing, while modern commonly used is purified, fried and salt-processed. The ancient records of Tribuli Fructus were spicy, bitter, and warm in nature, with modern research adding that it is slightly toxic. The main effects of ancient and modern times include treating wind disorders, improving vision, promoting muscle growth, and treating vitiligo. The mainstream base of ACS used throughout history is Astragalus complanatus. Ancient texts indicated ACS primarily originated from Shaanxi province. Today, the finest varieties come from Tongguan and Dali in Shaanxi. The medicinal part is the seed, traditionally harvested in autumn. Modern harvesting occurs in late autumn or early winter, followed by sun-drying. Ancient texts valued seeds with a fragrant aroma as superior, while modern standards prioritize plump, uniform and free of impurities. Traditional processing methods for ACS included frying until blackened and wine-frying, while modern practice commonly employs purification methods. In terms of medicinal properties, the ancient and modern records are sweet and warm in nature. Due to originally classified under Tribuli Fructus, its effects were thus regarded as equivalent to those of Tribuli Fructus, serving as the medicine for treating wind disorders, additional functions included tonifying the kidneys and treating vitiligo. The present record of its efficacy is to tonify the kidney and promote Yang, solidify sperm and reduce urine, nourish the liver and brighten the eye, etc. Based on the textual research results, it is suggested that when developing the famous classical formulas of Tribuli Fructus medicinal materials, we should pay attention to the specific reference object of Baijili, T. terrestris and A. complanatus should be identified and selected, and the processing method should be in accordance with the requirements of the formulas.
4.Lcn2 secreted by macrophages through NLRP3 signaling pathway induced severe pneumonia.
Mingya LIU ; Feifei QI ; Jue WANG ; Fengdi LI ; Qi LV ; Ran DENG ; Xujian LIANG ; Shasha ZHOU ; Pin YU ; Yanfeng XU ; Yaqing ZHANG ; Yiwei YAN ; Ming LIU ; Shuyue LI ; Guocui MOU ; Linlin BAO
Protein & Cell 2025;16(2):148-155
6.Discovery of selective HDAC6 inhibitors driven by artificial intelligence and molecular dynamics simulation approaches.
Xingang LIU ; Hao YANG ; Xinyu LIU ; Minjie MOU ; Jie LIU ; Wenying YAN ; Tianle NIU ; Ziyang ZHANG ; He SHI ; Xiangdong SU ; Xuedong LI ; Yang ZHANG ; Qingzhong JIA
Journal of Pharmaceutical Analysis 2025;15(8):101338-101338
Increasing evidence showed that histone deacetylase 6 (HDAC6) dysfunction is directly associated with the onset and progression of various diseases, especially cancers, making the development of HDAC6-targeted anti-tumor agents a research hotspot. In this study, artificial intelligence (AI) technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline, which combined Voting strategy based on compound-protein interaction (CPI) prediction models, cascade molecular docking, and molecular dynamic (MD) simulations. The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays. Among the identified compounds, Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity (IC50 = 5.41 nM) than that of tubastatin A (TubA) (IC50 = 15.11 nM), along with a favorable subtype selectivity profile (selectivity index ≈ 117.23 for HDAC1), which was further verified by the Western blot analysis. Additionally, Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells, exerting desirable antiproliferative activity (IC50 = 2.59 μM). Furthermore, based on long-term MD simulation trajectory, the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis, thereby elucidating its binding mechanism. Moreover, the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation, thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.
7.Analysis of the efficacy and safety of Saccharomyces boulardii in the treatment of pediatric diarrhea
Li-Li MOU ; Xiao-Dan ZHANG ; Lu LIU ; Chun-Hong CHEN ; Zhuo CHEN ; Hui YIN ; Mei-Xing YAN
The Chinese Journal of Clinical Pharmacology 2024;40(17):2575-2579
Objective To compare the efficacy and safety of Saccharomyces boulardii and other probiotics in the treatment of pediatric diarrhea.Methods Retrieved from PubMed,Embase,CBM,Wanfang data,CNKI and VIP,randomized controlled trial(RCTs)about Saccharomyces boulardii(treatment group)vs other probiotics(control group)were collected.After screening the literature,extracting data and evaluating the quality,Meta-analysis was performed by using RevMan 5.3 and Stata 17.0 software.Results A total of 30 RCTs were included,involving 3 082 children.Results of Meta-analysis showed there was no statistical significance in the duration of diarrhea[mean difference(MD)=-0.65,95%confidence interval(CI)=-1.44-0.14,P>0.05]or the total incidence of adverse reactions[odds ratio(OR)=0.85,95%CI=0.44-1.62,P>0.05].The total effective rate(OR=1.60,95%CI=1.08-2.36,P<0.05)and the number of stools(MD=-0.66,95%CI=-1.00--0.32,P<0.01)in the treatment group were significantly better than control group.There was statistically significant difference in the duration of diarrhea between the two groups treated with diarrhea with fever(MD=1.81,95%CI=1.12-2.49,P<0.01)and rotavirus gastroenteritis(MD=-0.92,95%CI=-1.20--0.64,P<0.01).In the treatment of diarrhea with fever,the duration of diarrhea in the control group was significantly shorter than that in the treatment group.The duration of diarrhea in the treatment group was significantly shorter than that control group.At the same time,the duration of diarrhea in children with diarrhea treated with treatment group was significantly shorter than that of control group Bifidobacterium tetragenous viable(MD=-0.84,95%CI=-1.09--0.58,P<0.01)and control group combined Bacillus subtilis and Enterococcus faecium enteric-coated(MD=-1.35,95%CI=-2.30-0.39,P<0.01).Conclusion The safety of Saccharomyces boulardii are similar to other probiotics.The efficacy and the number of stools with Saccharomyces boulardii are significantly better than other probiotics in the treatment of diarrhea.The duration of diarrhea in Saccharomyces boulardii group was significantly shorter than other probiotics,while in the treatment of antibiotic-associated diarrhea,the duration of diarrhea of Saccharomyces boulardii was the same as that of other probiotics.However,the duration of diarrhea in children with diarrhea treated with Saccharomyces boulardii was significantly longer than other probiotics.
8.Research progress on the roles and inhibitors of deubiquitinase USP28 in tumors
Xing LI ; Bo-ya ZHANG ; Li-ting LU ; Yan WANG ; Shuai WEN ; Yong-jun ZANG ; Xiang-ming XU ; Yi MOU
Acta Pharmaceutica Sinica 2024;59(11):2941-2952
The deubiquitinases (DUBs), as the crucial peptidohydrolases in the ubiquitin system, can reverse and strictly regulate ubiquitination and play key roles in various biological processes, including the regulation of protein stability, cell signal transduction. Ubiquitin-specific protease 28 (USP28) involves multiple cancer-related signaling pathways by enhancing the stability of various cancer-related proteins, and is closely associated with the progression of colorectal, breast cancer, lung carcinomas, and pancreatic cancer. USP28 has been considered as a promising drug target in anticancer therapy, and the development of USP28 inhibitors has made some progress. In this article, we review the structure of USP28 and its interaction with substrates, discuss the research progress of USP28 in cancers and summarize the development of USP28 inhibitors.
9.Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients (version 2024)
Yao LU ; Yang LI ; Leiying ZHANG ; Hao TANG ; Huidan JING ; Yaoli WANG ; Xiangzhi JIA ; Li BA ; Maohong BIAN ; Dan CAI ; Hui CAI ; Xiaohong CAI ; Zhanshan ZHA ; Bingyu CHEN ; Daqing CHEN ; Feng CHEN ; Guoan CHEN ; Haiming CHEN ; Jing CHEN ; Min CHEN ; Qing CHEN ; Shu CHEN ; Xi CHEN ; Jinfeng CHENG ; Xiaoling CHU ; Hongwang CUI ; Xin CUI ; Zhen DA ; Ying DAI ; Surong DENG ; Weiqun DONG ; Weimin FAN ; Ke FENG ; Danhui FU ; Yongshui FU ; Qi FU ; Xuemei FU ; Jia GAN ; Xinyu GAN ; Wei GAO ; Huaizheng GONG ; Rong GUI ; Geng GUO ; Ning HAN ; Yiwen HAO ; Wubing HE ; Qiang HONG ; Ruiqin HOU ; Wei HOU ; Jie HU ; Peiyang HU ; Xi HU ; Xiaoyu HU ; Guangbin HUANG ; Jie HUANG ; Xiangyan HUANG ; Yuanshuai HUANG ; Shouyong HUN ; Xuebing JIANG ; Ping JIN ; Dong LAI ; Aiping LE ; Hongmei LI ; Bijuan LI ; Cuiying LI ; Daihong LI ; Haihong LI ; He LI ; Hui LI ; Jianping LI ; Ning LI ; Xiying LI ; Xiangmin LI ; Xiaofei LI ; Xiaojuan LI ; Zhiqiang LI ; Zhongjun LI ; Zunyan LI ; Huaqin LIANG ; Xiaohua LIANG ; Dongfa LIAO ; Qun LIAO ; Yan LIAO ; Jiajin LIN ; Chunxia LIU ; Fenghua LIU ; Peixian LIU ; Tiemei LIU ; Xiaoxin LIU ; Zhiwei LIU ; Zhongdi LIU ; Hua LU ; Jianfeng LUAN ; Jianjun LUO ; Qun LUO ; Dingfeng LYU ; Qi LYU ; Xianping LYU ; Aijun MA ; Liqiang MA ; Shuxuan MA ; Xainjun MA ; Xiaogang MA ; Xiaoli MA ; Guoqing MAO ; Shijie MU ; Shaolin NIE ; Shujuan OUYANG ; Xilin OUYANG ; Chunqiu PAN ; Jian PAN ; Xiaohua PAN ; Lei PENG ; Tao PENG ; Baohua QIAN ; Shu QIAO ; Li QIN ; Ying REN ; Zhaoqi REN ; Ruiming RONG ; Changshan SU ; Mingwei SUN ; Wenwu SUN ; Zhenwei SUN ; Haiping TANG ; Xiaofeng TANG ; Changjiu TANG ; Cuihua TAO ; Zhibin TIAN ; Juan WANG ; Baoyan WANG ; Chunyan WANG ; Gefei WANG ; Haiyan WANG ; Hongjie WANG ; Peng WANG ; Pengli WANG ; Qiushi WANG ; Xiaoning WANG ; Xinhua WANG ; Xuefeng WANG ; Yong WANG ; Yongjun WANG ; Yuanjie WANG ; Zhihua WANG ; Shaojun WEI ; Yaming WEI ; Jianbo WEN ; Jun WEN ; Jiang WU ; Jufeng WU ; Aijun XIA ; Fei XIA ; Rong XIA ; Jue XIE ; Yanchao XING ; Yan XIONG ; Feng XU ; Yongzhu XU ; Yongan XU ; Yonghe YAN ; Beizhan YAN ; Jiang YANG ; Jiangcun YANG ; Jun YANG ; Xinwen YANG ; Yongyi YANG ; Chunyan YAO ; Mingliang YE ; Changlin YIN ; Ming YIN ; Wen YIN ; Lianling YU ; Shuhong YU ; Zebo YU ; Yigang YU ; Anyong YU ; Hong YUAN ; Yi YUAN ; Chan ZHANG ; Jinjun ZHANG ; Jun ZHANG ; Kai ZHANG ; Leibing ZHANG ; Quan ZHANG ; Rongjiang ZHANG ; Sanming ZHANG ; Shengji ZHANG ; Shuo ZHANG ; Wei ZHANG ; Weidong ZHANG ; Xi ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Xiaojun ZHANG ; Guoqing ZHAO ; Jianpeng ZHAO ; Shuming ZHAO ; Beibei ZHENG ; Shangen ZHENG ; Huayou ZHOU ; Jicheng ZHOU ; Lihong ZHOU ; Mou ZHOU ; Xiaoyu ZHOU ; Xuelian ZHOU ; Yuan ZHOU ; Zheng ZHOU ; Zuhuang ZHOU ; Haiyan ZHU ; Peiyuan ZHU ; Changju ZHU ; Lili ZHU ; Zhengguo WANG ; Jianxin JIANG ; Deqing WANG ; Jiongcai LAN ; Quanli WANG ; Yang YU ; Lianyang ZHANG ; Aiqing WEN
Chinese Journal of Trauma 2024;40(10):865-881
Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.
10.Comparison of clinical efficacy of TMF and TDF in the treatment of hepatitis B liver fibrosis
Yingyuan ZHANG ; Chunyan MOU ; Danqing XU ; Yuanzhen WANG ; Lixian CHANG ; Chunyun LIU ; Weikun LI ; Hong-Yan WEI ; Li LIU
The Journal of Practical Medicine 2024;40(22):3215-3220
Objective This study is to explore the clinical efficacy and common adverse reactions of PEG-IFN α-2b combined with TMF and TDF in the treatment of hepatitis B liver fibrosis,and provide more clinical reference for the treatment of chronic hepatitis B.Methods From January 2022 to December 2023,we selected 130 patients with chronic hepatitis B liver fibrosis who were admitted to Kunming Third People's Hospital.Divided into TMF combined group and TDF combined group,the virus reduction level,virus response rate,liver fibrosis four items,instantaneous elastography(FibroScan)and other indicators were compared between the two groups of patients after 48 weeks of treatment.The changes in liver fibrosis grading and adverse reactions before and after treatment were also compared.Results After 48 weeks of treatment,the TMF combined group showed a significant increase in HBV DNA seroconversion rate and HBeAg seroconversion rate compared to the TDF combined group,with statistical significance(P<0.05).However,there was no statistically significant difference in HBsAg seroconversion rate between the two groups of patients(P>0.05).After 48 weeks of treatment,the TMF combined group showed more significant efficacy in reducing the levels of HA,PC Ⅲ,Ⅳ-C,and LN,with a significant difference(P<0.05);After 48 weeks of treatment,both groups of patients showed improvement in the degree of liver tissue fibrosis.Compared with the TDF combined group,the TMF combined group had a more significant effect on tissue improvement.After 48 weeks of treatment,the incidence of dyslipidemia,hypothyroidism,and diarrhea was higher in the TMF combined group than in the TDF combined group(P<0.05);After 48 weeks of treatment,there was no statistically significant difference in the incidence of gingival bleeding,anemia,and thrombocytopenia between the two groups of patients(P>0.05);The incidence of elevated uric acid and joint pain in the TDF combined group was higher than that in the TMF combined group after 48 weeks of treatment(P<0.05).Conclusion TMF combined with PEG-IFN α-2b has better clinical efficacy in treating chronic hepatitis B,strong antiviral ability,greater inhibition of liver fibrosis,good drug safety,better prognosis,and can provide more effective medication basis for clinical cure of hepatitis B.

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