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Efficacy and Safety of Bufei Jiedu Granules in Treating Multidrug-Resistant Pulmonary Tuberculosis:A Multi-center,Double-Blinded and Randomized Controlled Trial

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Chinese Journal of Integrative Medicine 2024年第7期30卷 579-587页

作者： zhang Shao-yan QIU Lei zhang Shun-xian XIAO He-ping CHU Nai-hui zhang Xia zhang Hui-qiang ZHENG Pei-yong zhang Hui-yong LU Zhen-hui institute of Respiratory Diseases Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai200032China clinical Research Center Shanghai University of Traditional Chinese MedicineShanghai200032China Department of Tuberculosis Shanghai Pulmonary HospitalTongji UniversityShanghai200433China Department of Tuberculosis Beijing Chest HospitalCapital Medical UniversityBeijing101100China Department of Tuberculosis the Second Hospital of NanjingNanjing210003China Department of Tuberculosis the First Hospital Affiliated to Xinxiang Medical CollegeXinxiangHenan Province453100China

Objective: To assess the efficacy and safety of Bufei Jiedu(BFJD) Granules as adjuvant therapy for patients with multidrug-resistant pulmonary tuberculosis(MDR-PTB). Methods: A large-scale, multi-center, double-blinded, and randomized controlled trial was conducted in 18 sentinel hospitals in China from December 2012 to December 2016. A total of 312 MDR-PTB patients were randomly assigned to BFJD Granules or placebo groups(1:1) using a stratified randomization method, which both received the long-course chemotherapy regimen for 18 months(6 Am-Lfx-P-Z-Pto, 12 Lfx-P-Z-Pto). Meanwhile, patients in both groups also received BFJD Granules or placebo twice a day for a total of 18 months, respectively. The primary outcome was cure rate. The secondary outcomes included time to sputum-culture conversion, changes in lung cavities and quality of life(QoL) of patients. Adverse reactions were monitored during and after the trial. Results: A total of 216 cases completed the trial, 111 in the BFJD Granules group and 105 in the placebo group. BFJD Granules, as adjuvant treatment, increased the cure rate by 13.6% at the end of treatment, compared with the placebo(58.4% vs. 44.8%, P=0.02), and accelerated the median time to sputum-culture conversion(5 months vs. 11 months). The cavity closure rate of the BFJD Granules group(50.6%, 43/85) was higher than that of the placebo group(32.1%, 26/81;P=0.02) in patients who completed the treatment. At the end of the intensive treatment, according to the 36-item Short Form, the BFJD Granules significantly improved physical functioning, general health, and vitality of patients relative to the placebo group(all P<0.01). Overall, the death rates in the two groups were not significantly different;5.1%(8/156) in the BFJD Granules group and 2.6%(4/156) in the placebo group. Conclusions: Supplementing BFJD Granules with the long-course chemotherapy regimen significantly increased the cure rate and cavity closure rate, and rapidly improved QoL of pati

关键词： alternative medicine Chinese herbal formula Bufei Jiedu Granules multidrug-resistant tuberculosis long-course chemotherapy regimen randomized controlled trial

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Vitamin D binding protein in psychiatric and neurological disorders:Implications for diagnosis and treatment

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Genes & Diseases 2024年第5期11卷 324-334页

作者： Ling Li Bing Han Yan Kong Gaojia zhang Zhijun zhang Research Institution of Neuropsychiatry School of MedicineSoutheast UniversityNanjingJiangsu 210009China Department of Neurology Affiliated Zhongda HospitalNanjingJiangsu 210009China Department of pharmacology Jiangsu Provincial Key Laboratory of Critical Care MedicineSchool of MedicineSoutheast UniversityNanjingJiangsu 210009China Department of Biochemistry and Molecular Biology School of MedicineSoutheast UniversityNanjingJiangsu 210009China Brain Cognition and Brain Disease institute Department of Mental Health and Public HealthFaculty of Life and Health SciencesShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China

Vitamin D binding protein(VDBP)serves as a key transporter protein responsible for binding and delivering vitamin D and its metabolites to target *** plays a crucial part in the inflammatory reaction following tissue damage and is engaged in actin *** research has shed light on its potential role in various diseases,leading to a growing interest in understanding the implications of VDBP in psychiatric and neurological *** purpose of this review was to provide a summary of the existing understanding regarding the involvement of VDBP in neurological and psychiatric *** examining the intricate interplay between VDBP and these disorders,this review contributes to a deeper understanding of underlying mechanisms and potential therapeutic *** gained from the study of VDBP could pave the way for novel strategies in the diagnosis,prognosis,and treatment of psychiatric and neurological disorders.

关键词： Neurological disorder Polymorphism Psychiatric disorder Structure Vitamin D binding protein

Minimizing the ratio of ionizable lipid in lipid nanoparticles for in vivo base editing

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National Science Review 2024年第6期11卷 285-293页

作者： Qiubing Chen Xuebin Wang Yizhou zhang Ming Tian Junyi Duan Ying zhang Hao Yin Departments of Urology and Laboratory Medicine Frontier Science Center for Immunology and Metabolism Medical Research InstituteZhongnan Hospital of Wuhan UniversityWuhan University State Key Laboratory of Virology Tai Kang Center for Life and Medical Sciences Tai Kang Medical SchoolWuhan University Department of Rheumatology and Immunology Zhongnan Hospital of Wuhan UniversityWuhan University Wuhan Research Center for Infectious Diseases and Cancer Chinese Academy of Medical Sciences RNA institute Wuhan University

Lipid nanoparticles(LNPs) have gained clinical approval as carriers for both siRNA and mRNA. Among the crucial components of LNPs, ionizable lipids play a pivotal role in determining the efficiency of RNA delivery. In this study, we synthesized a series of ionizable lipids, denoted as HTO, with a higher count of hydroxyl groups compared to SM-102. Remarkably, LNPs based on HTO12 lipid demonstrated comparable mRNA delivery efficiency and biosafety to those based on SM-102. However, the former reduced the ratio of ionizable lipid/total lipids to mRNA in LNPs by 2.5 times compared to SM-102. The HTO12 LNP efficiently encapsulated adenine base editor mRNA and sgRNA targeting Pcsk9, leading to substantial gene editing within the liver of mice and effective reduction of the target protein. Our study underscores that ionizable lipids with multiple hydroxyl groups may facilitate an improved lipid-to-mRNA ratio to minimize the dosage of ionizable lipids for in vivo delivery.

关键词： ionizable lipid lipid nanoparticle mRNA delivery base editor delivery Pcsk9

Hepatitis B virus infection, infertility, and assisted reproduction

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第8期25卷 672-685页

作者： Lingjian zhang Fangfang zhang Zhiyuan MA Jie JIN Department of Infectious Diseases Affiliated Hangzhou First People’s HospitalSchool of MedicineZhejiang UniversityHangzhou 310003China Women’s Hospital School of MedicineZhejiang UniversityHangzhou 310003China Key Laboratory of clinical Cancer pharmacology and Toxicology Research of Zhejiang Province Affiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhou 310003China

Background:Hepatitis B virus(HBV)is one of the most widespread viruses worldwide and a major cause of hepatitis,cirrhosis,and hepatocellular *** studies have revealed the impacts of HBV infection on *** increasing number of infertile couples with chronic hepatitis B(CHB)virus infection choose assisted reproductive technology(ART)to meet their fertility *** the high prevalence of HBV,the effects of HBV infection on assisted reproduction treatment remain limited and ***:The aim of this study was to provide a comprehensive overview of the effect of HBV infection on fertility and discuss its effects on pregnancy outcomes,vertical transmission,pregnancy complications,and viral activity during ART ***:We conducted a literature search in PubMed for studies on HBV infection and ART published from 1996 to ***:HBV infection negatively affected fertility in both males and *** research shows that HBV infection may increase the risk of pregnancy complications in couples undergoing assisted reproduction *** impact of HBV infection on the pregnancy outcomes of ART is still *** evidence does not support that ART increases the risk of vertical transmission of HBV,while relevant studies are *** the development of ART,the risk of HBV reactivation(HBVr)is increasing,especially due to the wide application of immunosuppressive ***:Regular HBV infection screening and HBVr risk stratification and management are essential to prevent HBVr during *** determination of optimal strategy and timing of prophylactic anti-HBV therapy during ART still needs further investigation.

关键词： Assisted reproductive technology(ART) Hepatitis B virus(HBV) Immunosuppressive agent Pregnancy

基于NF-κB信号通路天然产物治疗特应性皮炎的研究进展

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中国实验方剂学杂志 2024年第4期30卷 271-280页

作者：李想董玲玲郭涛张理涛天津中医药大学研究生院天津301617 天津市中医药研究院附属医院天津300120

特应性皮炎是由内外多因素共同作用的慢性、复发性、炎症性、瘙痒性皮肤病,位居全球皮肤疾病负担首位。由于传统治疗和生物制剂的不良反应及高成本问题,天然产物的开发备受关注。核转录因子-κB(NF-κB)信号通路是抗炎和免疫调节的重要... 详细信息

特应性皮炎是由内外多因素共同作用的慢性、复发性、炎症性、瘙痒性皮肤病,位居全球皮肤疾病负担首位。由于传统治疗和生物制剂的不良反应及高成本问题,天然产物的开发备受关注。核转录因子-κB(NF-κB)信号通路是抗炎和免疫调节的重要途径,故基于NF-κB信号通路系统,总结了黄酮类、生物碱、酚类、萜类、香豆素类、糖苷类、蒽醌类等天然产物的药理学作用与分子机制,以期为天然产物的开发提供一定指导。目前众多基础研究显示出天然产物具有较高的安全性和有效性,并通过口服或外用的给药方式及与磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)、丝裂原活化蛋白激酶(MAPK)、核转录因子E2相关因子2(Nrf2)、高迁移率族蛋白B1(HMGB1)/晚期糖基化终产物受体(RAGE)、核苷酸结合寡聚结构域样受体蛋白3(NLRP3)等信号通路相互串扰的复杂药理学网络途径,发挥抗炎、抗过敏、抗氧化应激等作用,最终逆转特应性皮炎的病理改变。但值得注意的是,天然产物的临床应用转化尚相对不足,仍需更多更为严谨的临床试验加以验证。现有的基础试验及临床证据证明天然产物可能基于NF-κB信号通路发挥改善特应性皮炎的作用,这对评价天然活性物质的潜在机制提供依据,也为药物的开发提供了更多潜在候选者。

关键词：天然产物特应性皮炎核转录因子-κB(NF-κB)信号通路综述

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IL-13/IL-13RA2 signaling promotes colorectal cancer stem cell tumorigenesis by inducing ubiquitinated degradation of p53

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Genes & Diseases 2024年第1期11卷 495-508页

作者： Baoyu He Jing Liang Qianqian Qin Yuqin zhang Shuo Shi Jinghe Cao Zhixin zhang Qingli Bie Rou Zhao Li Wei Baogui zhang Bin zhang Department of Laboratory Medicine Affiliated Hospital of Jining Medical UniversityJining Medical UniversityJiningShandong 272000China Postdoctoral Mobile Station of Shandong University of Traditional Chinese Medicine JinanShandong 250355China Department of Reproductive Medicine Affiliated Hospital of Jining Medical UniversityJining Medical UniversityJiningShandong 272000China Department of Gastrointestinal Surgery Affiliated Hospital of Jining Medical UniversityJining Medical UniversityJiningShandong 272000China institute of Forensic Medicine and Laboratory Medicine Jining Medical UniversityJiningShandong 272067China

Cancer stem cells(CSCs)are considered tumor-initiating cells and the main drivers of disease *** these rare cancer cells,however,remains challenging with respect to therapeutic ***,we report the up-regulation of IL-13RA2 expression in colorectal cancer(CRC)tissues and spheroid *** expression of IL-13RA2 was positively correlated with canonical stemness markers in *** further demonstrated that the level of IL-13 was up-regulated in the serum of CRC ***,recombinant IL-13(rIL13)stimulation promoted the sphere formation,proliferation,and migration of CRC cells in vitro and enhanced tumorigenesis in *** phenotype could be reversed by knocking down ***,IL-13 activated autophagy by inducing LC3I/LC3II transformation in CRC-CSCs,which was crucial for the biological functions of *** further demonstrated that IL-13RA2 acted as a modular link of the E3 ligase UBE3C and the substrate p53 protein,enhancing the interaction of UBE3C and p53,thereby inducing the K48-linked ubiquitination of *** conclusion,the IL-13/IL-13RA2 signaling cascade promotes CRC-CSC self-renewal and tumorigenesis by inducing p53 ubiquitination,adding an important layer to the connection between IL-13 and p53,which can be translated into novel targeted therapies.

关键词： Autophagy Colorectal cancer stem cells IL-13/IL-13RA2 signaling p53

Comparison of Ex‑PRESS implantation versus trabeculectomy combined with phacoemulsification in primary open‑angle glaucoma:a retrospective in vivo confocal microscopy study

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Eye and Vision 2024年第2期10卷 1-11页

作者： Yuqiao zhang Beiting He Yulin zhang Jin Zeng Yanlei Chen Yongyi Niu Honghua Yu Yongjie Qin Hongyang zhang Department of Ophthalmology Guangdong Eye InstituteGuangdong Academy of Medical SciencesGuangdong Provincial People’s HospitalNo.106 Zhongshan Er RoadGuangzhou 510080China Shantou University Medical College ShantouChina The Second School of clinical Medicine Southern Medical UniversityGuangzhouChina Department of Ophthalmology School of MedicineSouth China University of TechnologyGuangzhouChina

Background:To compare the efficacy of Ex-PRESS implantation versus trabeculectomy combined with ***:A retrospective 12-month study on patients with coincident primary open-angle glaucoma(POAG)and *** patients underwent combined phacoemulsification and Ex-PRESS implant(Phaco-ExPRESS,n=35)or phacotrabeculectomy(Phaco-Trab,n=35).The morphological structures of the filtering bleb were examined by slitlamp,anterior segment optical coherence tomography(AS-OCT)and in vivo confocal microscopy(IVCM).Complete success was defined as postoperative intraocular pressure(IOP)<18 mmHg without the use of anti-glaucoma *** success was defined as postoperative IOP<18 mmHg with or without anti-glaucoma *** data were collected preoperatively and postoperatively at 2 weeks,1 month,3 months,6 months,and 12 ***:No significant difference in the variables such as age,IOP and perimetry was found between the groups of Phaco-ExPRESS and *** the one-year postoperative visit for filtering blebs,Phaco-ExPRESS increased the mean area of epithelial microcysts significantly from 0.10±0.05 to 0.20±0.09μm^(2)perμm^(2),while Phaco-Trab decreased the mean area significantly from 0.08±0.04 to 0.04±0.06μm^(2)perμm^(2).Notably,the hyperreflective dots detected by IVCM decreased by 84.9%in Phaco-ExPRESS but increased by 36.3%in *** hyperreflective dots were further identified as neutrophil-and monocyte-like *** number of these cells were negatively correlated with the microcysts area(r=−0.7,P<0.01)but positively associated with the grade of connective tissue(r=0.5,P<0.01).By creating different microstructural changes in the filtering blebs,Phaco-ExPRESS produced a higher complete success rate(84.9%vs.41.2%,P<0.01)and significant decrease in the number of anti-glaucoma medications(P<0.01)when compared with those in ***,the qualified success showed no significant difference between the two groups(

关键词： POAG Ex-PRESS Phacoemulsification Confocal microscopy

Integrated bulk and single-cell transcriptome data identify clinically relevant cell populations in clear cell renal cell carcinoma

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Genes & Diseases 2024年第1期11卷 42-45页

作者： Pingbao zhang Pu zhang Jun Gao Xiaosong Li Chengcheng Wei Weihui Liu QingLiu He Yuan zhang Department of Urology Zhongshan HospitalFudan UniversityShanghai 200032China Department of Urology Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China Department of Liver Surgery and Transplantation Liver Cancer InstituteZhongshan HospitalFudan UniversityShanghai 200032China clinical Molecular Medicine Testing Center The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Urology The Second Affiliated Hospital of Fujian Medical UniversityQuanzhouFujian 362000China Department of Nephrology Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan 610072China

Renal cell carcinoma,which consists of three main histological subtypes,namely,clear cell renal cell carcinoma(ccRCC),papillary RCC(pRCC),and chromophobe RCC(chRCC),accounts for most kidney cancer *** accounts for approximately 85%of all RcC cases,1 and it is a malignant tumor with multiple molecular features and a poor *** have shown that ccRCC is one of the most immune and vaso-invasive cancer types.2 Considering that ccRCC is not sensitive to either radiotherapy or chemotherapy,targeted therapies.

关键词： chemotherapy cancer cases

维得利珠单抗治疗炎症性肠病患者疗效评价的回顾性研究

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中国临床药理学与治疗学 2024年第8期29卷 899-906页

作者：李培培武岳张贤政张玲玲安徽中医药大学第一附属医院药学部安徽中医药大学第一附属医院肛肠外科安徽医科大学临床药理研究所抗炎免疫药物教育部重点实验室安徽合肥230032

目的:评价维得利珠单抗(VDZ)治疗炎症性肠病的疗效和安全性。方法:回顾性收集2021年3月至2023年8月本院肛肠科收治的使用VDZ治疗的炎症性肠病(IBD)患者共25例[溃疡性结肠炎(UC)13例、克罗恩病(CD)12例]的病例资料。给予静脉输注VDZ,在第... 详细信息

目的:评价维得利珠单抗(VDZ)治疗炎症性肠病的疗效和安全性。方法:回顾性收集2021年3月至2023年8月本院肛肠科收治的使用VDZ治疗的炎症性肠病(IBD)患者共25例[溃疡性结肠炎(UC)13例、克罗恩病(CD)12例]的病例资料。给予静脉输注VDZ,在第0、2、6周给药300 mg诱导缓解治疗,随后每8周300 mg静脉给药一次维持缓解治疗,用药30周后进行评价。主要疗效指标包括临床应答率、临床缓解率、内镜缓解率,次要疗效指标包括营养状况指标[体质量(Wt)、血红蛋白(HGB)、白蛋白(ALB)、血细胞比容(HCT)]、炎症程度指标[超敏C反应蛋白(hs-CRP)、红细胞沉降率(ESR)]。记录VDZ治疗期间出现的所有不良反应。结果:IBD患者使用VDZ治疗6周和14周的总临床应答率分别为32%和60%,用药14周和30周的总临床缓解率分别为16%和36%,用药30周的总内镜缓解率为16%。VDZ对于治疗UC和CD的临床应答率和临床缓解率无统计学差异。与用药前相比,UC患者用药30周后体质量明显增加,营养指标HCT%、ALB、HGB水平明显好转,炎症指标ESR水平显著下降;CD患者用药30周与用药前相比,体质量明显增加,炎症指标hs-CRP、营养指标HCT%、ALB、HGB水平显著改善。1例患者在第3次输注VDZ后出现白细胞计数升高外,未发生其他不良反应。结论:VDZ作为IBD患者的诱导和维持治疗用药,能够显著减轻IBD患者肠道炎症反应、缓解患者临床症状、改善患者营养状况、提高患者生活质量,且安全性良好。

关键词：炎症性肠病维得利珠单抗疗效安全性

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