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Journal of Pharmaceutical Analysis 2024年第4期14卷 615-618页

作者： Yue Liu Mengjia Li Xing Fu Yi Zhang Ce Tang State Key Laboratory of Southwestern Chinese Medicine Resources School of Ethnic MedicineChengdu University of Traditional Chinese MedicineChengdu611137China Meishan Hospital of Chengdu University of Traditional Chinese Medicine MeishanSichuan620010China Innovative institute of Chinese Medicine and pharmacy Chengdu University of Traditional Chinese MedicineChengdu611137China

The dried roots of Aconitum pendulum Busch are the major source of a commonly used Tibetan medicine,namely Tiebangchui(TBC)(Fig.S1).However,raw TBC contains a large amount of high toxic diester-diterpenoid alkaloids(DDAs),and the improper use would cause arrhythmia,irreversible cardiovascular damages,and even death.“Paozhi”,an appropriate processing method,is the essential prerequisite for the safe clinical application of ***-decocting and sand-frying are commonly used processing methods for toxicity attenuation and efficacy preservation for TBC.

关键词： dried irreversible roots

Immunostimulatory gene therapy combined with checkpoint blockade reshapes tumor microenvironment and enhances ovarian cancer immunotherapy

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Acta Pharmaceutica Sinica B 2024年第2期14卷 854-868页

作者： Yunzhu Lin Xiang Wang Shi He Zhongxin Duan Yunchu Zhang Xiaodong Sun Yuzhu Hu Yuanyuan Zhang Zhiyong Qian Xiang Gao Zhirong Zhang Key Laboratory of Drug Targeting and Drug Delivery Systems Ministry of EducationWest China School of PharmacySichuan UniversityChengdu 610041China Department of pharmacy Evidence-based Pharmacy CenterWest China Second University HospitalKey Laboratory of Birth Defects and Related Diseases of Women and ChildrenSichuan UniversityChengdu 610041China Department of Neurosurgery and institute of Neurosurgery State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalWest China Medical SchoolSichuan University and Collaborative Innovation Center for BiotherapyChengdu 610041China Department of Radiation Oncology State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalWest China Medical SchoolSichuan University and Collaborative Innovation Center for BiotherapyChengdu 610041China West China School of Basic Medical Sciences&Forensic Medicine Sichuan UniversityChengdu 610041China

Immune evasion has made ovarian cancer notorious for its refractory features, making the development of immunotherapy highly appealing to ovarian cancer treatment. The immune-stimulating cytokine IL-12 exhibits excellent antitumor activities. However, IL-12 can induce IFN-γ release and subsequently upregulate PDL-1 expression on tumor cells. Therefore, the tumor-targeting folate-modified delivery system F-DPC is constructed for concurrent delivery of IL-12 encoding gene and small molecular PDL-1 inhibitor(i PDL-1) to reduce immune escape and boost anti-tumor immunity. The physicochemical characteristics, gene transfection efficiency of the F-DPC nanoparticles in ovarian cancer cells are analyzed. The immune-modulation effects of combination therapy on different immune cells are also studied. Results show that compared with non-folate-modified vector, folate-modified F-DPC can improve the targeting of ovarian cancer and enhance the transfection efficiency of p IL-12. The underlying anti-tumor mechanisms include the regulation of T cells proliferation and activation, NK activation,macrophage polarization and DC maturation. The F-DPC/p IL-12/i PDL-1 complexes have shown outstanding antitumor effects and low toxicity in peritoneal model of ovarian cancer in mice. Taken together, our work provides new insights into ovarian cancer immunotherapy. Novel F-DPC/p IL-12/i PDL-1 complexes are revealed to exert prominent anti-tumor effect by modulating tumor immune microenvironment and preventing immune escape and might be a promising treatment option for ovarian cancer treatment.

关键词： IL-12encodinggene Checkpointblocker Nanoparticles Targeted delivery Tumormicroenvironment Immune escape Ovarian cancer Immunotherapy

The role of botanical triterpenoids and steroids in bile acid metabolism,transport,and signaling:Pharmacological and toxicological implications

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3385-3415页

作者： Zichen Luo Wei Zhou Tong Xie Weichen Xu Chen Shi Zihan Xiao Yu Si Yan Ma Qingling Ren Liuqing Di Jinjun Shan Medical Metabolomics Center Institute of PediatricsJiangsu Key Laboratory of Children’s Health and Chinese MedicineNanjing University of Chinese MedicineNanjing 210023China State Key Laboratory of Natural Medicines School of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjing 210009China Jiangsu CM Clinical Medicine Innovation Center for Obstetrics Gynecologyand ReproductionAffiliated Hospital of Nanjing University of Chinese MedicineNanjing 210001China National institute of Biological Sciences Beijing 102206China Jiangsu Engineering Research Center for Efficient Delivery System of TCM School of PharmacyNanjing University of Chinese MedicineNanjing 210023China

Bile acids(BAs)are synthesized by the host liver from cholesterol and are delivered to the intestine,where they undergo further metabolism by gut microbes and circulate between the liver and intestines through various *** serve to emulsify dietary lipids and act as signaling molecules,regulating the host’s metabolism and immune homeostasis through specific ***,disruptions in BA metabolism,transport,and signaling are closely associated with cholestasis,metabolic disorders,autoimmune diseases,and *** triterpenoids and steroids share structural similarities with BAs,and they have been found to modulate BA metabolism,transport,and signaling,potentially exerting pharmacological ortoxicological ***,we have updated the research progress on BA,with a particular emphasis on new-found microbial ***,the latest advancements in targeting BA metabolism and signaling for disease treatment are ***,the roles of botanical triterpenoids in BA metabolism,transport,and signaling are examined,analyzing their potential pharmacological,toxicological,or drug interaction effects through these ***,a research paradigm is proposed that utilizes the gut microbiota as a link to interpret the role of these important natural products in BA signaling.

关键词： Bile acid Triterpenoid Phytosterol Saponin Gut microbes Cholestasis Metabolic disorders Rheumatoid arthritis

Dynamic gut microbiome-metabolome in cationic bovine serum albumin induced experimental immune-complex glomerulonephritis and effect of losartan and mycophenolate mofetil on microbiota modulation

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Journal of Pharmaceutical Analysis 2024年第4期14卷 562-577页

作者： Wenying Shi Zhaojun Li Weida Wang Xikun Liu Haijie Wu Xiaoguang Chen Xunrong Zhou Sen Zhang State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing100050China State Key Laboratory of Functions and Applications of Medicinal Plants College of PharmacyGuizhou Provincial Engineering Technology Research Center for Chemical Drug R&DGuizhou Medical UniversityGuiyang550004China Department of Medicine Solna Center for Molecular MedicineKarolinska University Hospital and Karolinska InstituteStockholm17176Sweden Department of pharmacy The Second Affiliated Hospital of Guizhou University of Traditional Chinese MedicineGuiyang550001China

Dynamic changes in gut dysbiosis and metabolomic dysregulation are associated with immune-complex glomerulonephritis(ICGN).However,an in-depth study on this topic is currently ***,we report an ICGN model to address this *** was induced via the intravenous injection of cationized bovine serum albumin(c-BSA)into Sprague-Dawley(SD)rats for two weeks,after which mycophenolate mofetil(MMF)and losartan were administered *** and six weeks after ICGN establishment,fecal samples were collected and 16S ribosomal DNA(rDNA)sequencing and untargeted metabolomic were *** microbiota transplantation(FMT)was conducted to determine whether gut normali-zation caused by MMF and losartan contributed to their renal protective effects.A gradual decline in microbial diversity and richness was accompanied by a loss of renal *** 18 genera were found to have significantly different relative abundances between the early and later stages,and Marvinbryantia and Allobaculum were markedly upregulated in both *** metabolomics indicated that the tryptophan metabolism was enhanced in ICGN,characterized by the overproduction of indole and kynurenic acid,while the serotonin pathway was *** of losartan and MMF ameliorated microbial dysbiosis and reduced the accumulation of indoxyl conjugates in *** using feces from animals administered MMF and losartan improved gut dysbiosis by decreasing the Firmicutes/Bacteroidetes(F/B)ratio but did not improve renal *** findings indicate that ICGN induces serous gut dysbiosis,wherein an altered tryptophan metabolism may contribute to its *** and losartan significantly reversed the gut microbial and metabolomic dysbiosis,which partially contributed to their renoprotective effects.

关键词： Immune-complex glomerulonephritis Gut microbiome Metabolomics Fecal microbiota transplant Tryptophan metabolism

Severe aconite poisoning successfully treated with veno-arterial extracorporeal membrane oxygenation:A case report

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World Journal of Clinical Cases 2024年第2期12卷 399-404页

作者： Saeko Kohara Yoshito Kamijo Ryoko Kyan Ichiro Okada Eiju Hasegawa Soichiro Yamada Koichi Imai Asuka Kaizaki-Mitsumoto Satoshi Numazawa Department of Critical Care Medicine and Trauma National Hospital Organization Disaster Medical CenterTokyo 1900014Japan Department of Clinical Toxicology Saitama Medical UniversitySaitama 3500495Japan Saitama Prefectural institute of Public Health Saitama Prefectural Institute of Public HealthSaitama 3550133Japan Division of Toxicology Department of PharmacologyToxicology and TherapeuticsShowa University School of PharmacyTokyo 1428555Japan

BACKGROUND Most species of aconite contain highly toxic aconitines,the oral ingestion of which can be fatal,primarily because they cause ventricular *** describe a case of severe aconite poisoning that was successfully treated through venoarterial extracorporeal membrane oxygenation(VA-ECMO)and in which detailed toxicological analyses of the aconite roots and biological samples were performed using liquid chromatography-tandem mass spectrometry(LC-MS/MS).CASE SUMMARY A 23-year-old male presented to the emergency room with circulatory collapse and ventricular arrhythmia after ingesting approximately half of a root labeled,“Aconitum japonicum Thunb”.Two hours after arrival,VA-ECMO was initiated as circulatory collapse became refractory to antiarrhythmics and *** hours after arrival,an electrocardiogram revealed a return to sinus *** patient was weaned off VA-ECMO and the ventilator on hospital days 3 and 5,*** hospital day 15,he was transferred to a psychiatric *** other half of the root and his biological samples were toxicologically analyzed using LC-MS/MS,revealing 244.3 mg/kg of aconitine and 24.7 mg/kg of mesaconitine in the *** on admission contained 1.50 ng/mL of *** hospital day 2,neither were *** on admission showed 149.09 ng/mL of aconitine and 3.59 ng/mL of mesaconitine,but these rapidly decreased after hospital day *** The key to saving the life of a patient with severe aconite poisoning is to introduce VA-ECMO as soon as possible.

关键词： Aconite poisoning Fatal arrhythmia Veno-arterial extracorporeal membrane oxygenation Aconitine Mesaconitine Case report

A cross-sectional study to assess medication safety,knowledge,attitude,and practices regarding nutrition and medication among pregnant women

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Asian pacific Journal of Reproduction 2024年第3期13卷 115-119页

作者： Gauthami R Bipin Shaji Twinkle MJS Krishnapriya Radhakrishnan Reshma Kolar Juno Jerold Joel Nitte(Deemed to be University) NGSM Institute of Pharmaceutical Sciences(NGSMIPS)Department of Pharmacy PracticeDeralakatteMangaluruIndia Nitte(Deemed to be University) KS Hegde Medical Academy(KSHEMA)Department of Obstetrics and GynaecologyDeralakatteMangaluruIndia AJ institute of Medical Sciences and Research Centre Department of Community MedicineMangaluruKarnatakaIndia

Objective:To assess pregnant women's knowledge,attitude,and practice regarding nutrition and medication usage,analyse the prescribing pattern,and categorize them based on the Food and Drug Administration(FDA)***:A cross-sectional study was conducted with 264 pregnant women in the obstetrics and gynaecology department of a tertiary care hospital from October 2022 to August 2023.A knowledge,attitude,and practice(KAP)questionnaire was prepared in English language by the researchers and validated by an expert panel consisting of 12 *** validated questionnaire was then translated into regional languages,Kannada and *** reliability of the questionnaire was assessed with test-retest method with a representative sample population of 30 subjects(10 subjects for each language).The subjects'knowledge,attitude,and practice were evaluated using the validated KAP *** safety of the medication was assessed using the FDA drug safety classification for ***:The mean scores for nutritional and medication usage knowledge,attitude,and practice were 4.14±1.15,4.50±1.09,and 3.00±1.47,*** 30 prescribed medications,3 belong to category A(no risk in human studies),8 belong to category B(no risk in animal studies),18 belong to category C(risk cannot be ruled out)and 1 drug is not classified.A significant association was observed between medication knowledge and practice(r=0.159,P=0.010).Conclusions:Most of the study population knows the need to maintain good dietary and medication practices during *** pregnant women regarding diet and medication usage is crucial in maternal care.

关键词： Pregnancy Nutrition Medication Knowledge Practice Safe medication

Health behavior outcomes in stroke survivors prescribed wearables for atrial fibrillation detection stratified by age

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Journal of Geriatric Cardiology 2024年第3期21卷 323-330页

作者： Joanne Mathew Jordy Mehawej Ziyue Wang Taylor Orwig Eric Ding Andreas Filippaios Syed Naeem Edith Mensah Otabil Alex Hamel Kamran Noorishirazi IrinaRadu Jane Saczynski David D.McManus Khanh-Van Tran Division of Cardiovascular Medicine Department of MedicineUniversity of Massachusetts Chan Medical SchoolLake Avenue NorthWorcesterUSA Department of Internal Medicine Central Michigan UniversityMount PleasantUSA Department of pharmacy and Health Systems Sciences School of PharmacyNortheastern UniversityBostonUSA Department of Population and Quantitative Health Sciences University of Massachusetts Chan Medical SchoolLake Avenue NorthWorcesterUSA

BACKGROUND Smartwatches have become readily accessible tools for detecting atrial fibrillation(AF).There remains limited data on how they affect psychosocial outcomes and engagement in older *** examine the health behavior outcomes of stroke survivors prescribed smartwatches for AF detection stratified by *** We analyzed data from the Pulsewatch study,a randomized controlled trial that enrolled patients(≥50 years)with a history of stroke or transient ischemic attack and CHA2DS2-VASc≥*** participants were equipped with a cardiac patch monitor and a smartwatch-app dyad,while control participants wore the cardiac patch monitor for up to 44 *** evaluated health behavior parameters using standardized tools,including the Consumer Health Activation Index,the Generalized Anxiety Disorder questionnaire,the 12-Item Short Form Health Survey,and wear time of participants categorized into three age groups:Group 1(ages 50-60),Group 2(ages 61-69),and Group 3(ages 70-87).We performed statistical analysis using a mixedeffects repeated measures linear regression model to examine differences amongst age *** Comparative analysis between Groups 1,2 and 3 revealed no significant differences in anxiety,patient activation,perception of physical health and wear *** use of smartwatch technology was associated with a decrease in perception of mental health for Group 2 compared to Group 1(β=-3.29,P=0.046).CONCLUSION Stroke survivors demonstrated a willingness to use smartwatches for AF ***,among these study participants,the majority did not experience negative health behavior outcomes or decreased engagement as age increased.

关键词： prescribed stratified wear

Probing the dynamic thermodynamic resolution and biological activity of Cu(Ⅱ) and Pd(Ⅱ) complexes with Schiff base ligand derived from proline

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Chinese Chemical Letters 2024年第4期35卷 99-105页

作者： Tao Yu Vadim A.Soloshonok Zhekai Xiao Hong Liu Jiang Wang State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China School of pharmacy University of Chinese Academy of SciencesBeijing 100049China Department of Organic Chemistry Ⅰ Faculty of ChemistryUniversity of the Basque Country UPV/EHUSan Sebastian 20018Spain IKERBASQUE Basque Foundation for ScienceBilbao 48013Spain School of Pharmaceutical Science and Technology Hangzhou Institute for Advanced StudyUCASHangzhou 310024China Lingang Laboratory Shanghai 200031China

Schiff base metal complexes are of great importance in pharmaceutical science owing to their unique chemical properties, which enable them to exhibit diverse biological activities such as anti-bacterial,anti-oxidant, anti-inflammatory, and anti-tumor properties. Furthermore, Schiff base metal complexes can serve as reagents and catalysts in chemical reactions. This review aims to provide an overview of our recently published studies on Cu(Ⅱ) and Pd(Ⅱ) complexes derived from proline Schiff base ligands. We also discuss the potential applications of these metal complexes in the fields of antibacterial and chiral resolution.

关键词： Schiff bases Biological activity Tailor-made amino acids Asymmetric synthesis Chiral tridentate ligands Square-planar Cu(Ⅱ)-complexes Square-planar Pd(Ⅱ)-complexes

Nanomedicine integrating the lipidic derivative of 5-fluorouracil,miriplatin and PD-L1 si RNA for enhancing tumor therapy

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Chinese Chemical Letters 2024年第6期35卷 385-391页

作者： An Lu Yuhao Guo Yi Yan Lin Zhai Xiangyu Wang Weiran Cao Zijie Li Zhixia Zhao Yujie Shi Yuanjun Zhu Xiaoyan Liu Huining He Zhiyu Wang Jian-Cheng Wang Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems State Key Laboratory of Natural and Biomimetic DrugsSchool of Pharmaceutical SciencesPeking UniversityBeijing 100191China Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics School of PharmacyTianjin Medical UniversityTianjin 300070China Department of Immuno-oncology The Fourth Hospital of Hebei Medical UniversityShijiazhuang 050011China Department of pharmacy Clinical Trial Research CenterChina-Japan Friendship HospitalBeijing 100029China Laboratory of innovative formulations and pharmaceutical excipients Ningbo Institute of Marine MedicinePeking UniversityNingbo 315832China

Immunosuppressive microenvironments present critical problems in clinical *** regulate the tumor immune microenvironment for enhancing antitumor effect,a combination of immune checkpoint inhibitors(ICIs)with chemotherapeutics has been applied *** this study,miriplatin(MiPt),the lipidic derivative of 5-fluorouracil(Fu-OA),as well as the programmed death ligand 1(PD-L1)target si RNA(siPD-L1)were integrated into Lip-Pt/Fu@siPD-L1 nanoparticles(NPs)for *** vitro results showed that Lip-Pt/Fu@siPD-L1 NPs could exhibit effective siRNA gene silencing and promote the phagocytosis of tumor cells by ***,in vivo results revealed that LipPt/Fu@siPD-L1 NPs showed significantly higher anti-tumor efficiency than that of the physical mixing of Mi Pt,5-fluorouracil,and Lip@siPD-L1 NPs(delivery of siPD-L1 by liposomes).The best anti-tumor efficiency of Lip-Pt/Fu@siPD-L1 NPs resulted from the synergistic immunotherapeutic effects of Mi Pt and siPD-L1 based on the inhibition of CD47 expression and the downregulation of PD-L1 in tumor cells,which elicited a robust anti-tumor immune response through the activation of macrophage phagocytosis and immune checkpoint *** Lip-Pt/Fu@siPD-L1 NPs provide a potential strategy for tumor chemo-immunotherapy.

关键词： Chemo-immunotherapy Immune checkpoint inhibition Gene silencing Miriplatin Macrophage phagocytosis Nanotechnology

Rapid Simultaneous Determination of Four Ganoderic Acids in Ganoderma(Chinese Name:Lingzhi)by Direct Infusion-Multiple Reaction Monitoring Cubed

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Journal of Analysis and Testing 2024年第1期8卷 52-62页

作者： Nian Wu Bo Peng Ting Li Pengfei Tu Shengpeng Wang Bo Li Wenjing Liu Yuelin Song Modern Research Center for Traditional Chinese Medicine Beijing Research Institute of Chinese MedicineBeijing University of Chinese MedicineBeijing 100029China Amway(China)Botanical Research Center Wuxi 214011China State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoTaipa 999078China Amway(Shanghai)Innovation&Science Co. LtdShanghai 201508China School of pharmacy Henan University of Chinese MedicineZhengzhou 450046China

Attributing to the rapid demand expansion for the edible medicinal materials in the market,the limited throughput of highperformance liquid chromatography-multiple reaction monitoring(HPLC-MRM)cannot fully address the measurement workload for a huge number of testing ***,it is urgent to pursue more efficient approaches for the quality *** of the greater selectivity of MRM cubed(MRM^(3))over MRM,there might be a chance to omit the time-intensive LC *** current study,we attempted to develop a direct infusion(DI)-MRM^(3) program,and the applicability was thereafter assessed through simultaneous determination of four ganoderic acids(GAs)in one of the most famous tonic herbal medicines namely Ganoderma(Chinese name:Lingzhi).Primary parameters such as Q1>Q3>QLIT ion transitions,collision energy(CE),and excitation energy were optimized by programming online energy-resolved mass spectrometry with authentic compounds.A single DI-MRM measurement merely costed four minutes,and in spite of the wide occurrences of isomers,satisfactory selectivity was *** validation assays demonstrated the method to be sensitive,precise,accurate,and *** quantitative results from DI-MRM^(3) were also justified by conducting LC-MRM measurements in *** differences occurred for the content patterns between the two original sources namely Ganoderma lucidum and ***,and,moreover,either cultivar or harvest time showed dramatical influence on the quantitative features of the four targeted *** importantly,DI-MRM3 is a meaningful analytical option for rapid quantitative analysis of herbal medicines,because of the comparable reliability,nonetheless,less consumptions of both measurement time and solvent,compared with LC-MRM.

关键词： Direct infusion Multiple reaction monitoring cubed High-throughput quantitative analysis Ganoderic acids Ganoderma