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Interaction of major facilitator superfamily domain containing 2A with the blood-brain barrier

Neural Regeneration Research 2025年第8期20卷 2133-2152页

作者： Yilun Ma Taiwei Dong Fei Luan Juanjuan Yang Feng Miao Peifeng Wei College of Pharmacy and First clinical Medical College Shaanxi University of Chinese MedicineXianyangShaanxi ProvinceChina National Drug clinical trial Agency The Second Affiliated Hospital of Shaanxi University of Chinese Medicine/Xixian New District Central HospitalXi′anShaanxi ProvinceChina

The functional and structural integrity of the blood-brain barrier is crucial in maintaining homeostasis in the brain microenvironment;however,the molecular mechanisms underlying the formation and function of the blood-brain barrier remain poorly *** major facilitator superfamily domain containing 2A has been identified as a key regulator of blood-brain barrier *** plays a critical role in promoting and maintaining the formation and functional stability of the blood-brain barrier,in addition to the transport of lipids,such as docosahexaenoic acid,across the blood-brain ***,an increasing number of studies have suggested that major facilitator superfamily domain containing 2A is involved in the molecular mechanisms of blood-brain barrier dysfunction in a variety of neurological diseases;however,little is known regarding the mechanisms by which major facilitator superfamily domain containing 2A affects the blood-brain *** paper provides a comprehensive and systematic review of the close relationship between major facilitator superfamily domain containing 2A proteins and the blood-brain barrier,including their basic structures and functions,cross-linking between major facilitator superfamily domain containing 2A and the blood-brain barrier,and the in-depth studies on lipid transport and the regulation of blood-brain barrier *** comprehensive systematic review contributes to an in-depth understanding of the important role of major facilitator superfamily domain containing 2A proteins in maintaining the structure and function of the blood-brain barrier and the research progress to *** will not only help to elucidate the pathogenesis of neurological diseases,improve the accuracy of laboratory diagnosis,and optimize clinical treatment strategies,but it may also play an important role in prognostic *** addition,the effects of major facilitator superfamily domain containing 2A on blood-brain barrier lea

关键词： blood-brain barrier(BBB) caveolin-1 central nervous system docosahexaenoic acid endothelial cells lysophosphatidylcholine major facilitator superfamily domain containing 2A(MFSD2A) transcytosis

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Lipid droplets in the nervous system:involvement in cell metabolic homeostasis

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Neural Regeneration Research 2025年第3期20卷 740-750页

作者： Yuchen Zhang Yiqing Chen Cheng Zhuang Jingxuan Qi Robert Chunhua Zhao Jiao Wang School of Life Sciences Shanghai UniversityShanghaiChina School of Medicine Shanghai UniversityShanghaiChina Institute of Basic Medical Sciences Chinese Academy of Medical Sciences School of Basic MedicinePeking Union Medical CollegeBeijingChina Center of Excellence in Tissue Engineering Chinese Academy of Medical SciencesBeijingChina Beijing Key Laboratory of New Drug Development and clinical trial of Stem Cell Therapy BeijingChina

Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous *** droplet formation begins with the synthesis of neutral lipids in the endoplasmic ***,lipid droplets were recognized for their role in maintaining lipid metabolism and energy homeostasis;however,recent research has shown that lipid droplets are highly adaptive organelles with diverse functions in the nervous *** addition to their role in regulating cell metabolism,lipid droplets play a protective role in various cellular stress ***,lipid droplets exhibit specific functions in neurons and glial *** of lipid droplet formation leads to cellular dysfunction,metabolic abnormalities,and nervous system *** review aims to provide an overview of the role of lipid droplets in the nervous system,covering topics such as biogenesis,cellular specificity,and ***,it will explore the association between lipid droplets and neurodegenerative *** the involvement of lipid droplets in cell metabolic homeostasis related to the nervous system is crucial to determine the underlying causes and in exploring potential therapeutic approaches for these diseases.

关键词： Alzheimer's disease lipid droplet biogenesis lipid droplets lipid metabolism nervous system neurodegenerative disorders oxidative stress Parkinson's disease

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Antithetical impacts of deleterious LRP1B mutations in non-squamous and squamous NSCLCs on predicting benefits from immune checkpoint inhibitor alone or with chemotherapy over chemotherapy alone: retrospective analyses of the POPLAR/OAK and CHOICE-01 trial

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Science China Life Sciences 2025年第1期 249-262页

作者： Jinliang Wang Wenyong Zhou Yu Xu Jianchun Duan Qiaoxia Zhou Guoqiang Wang Leo Li Chunwei Xu Wenxian Wang Shangli Cai Zhijie Wang Jie Wang Department of Oncology The Fifth Medical Center of Chinese PLA General Hospital Department of Thoracic Surgery Shanghai Chest HospitalSchool of MedicineShanghai Jiao Tong University Burning Rock Biotech CAMS Key Laboratory of Translational Research on Lung Cancer State Key Laboratory of Molecular OncologyDepartment of Medical OncologyNational Cancer Center/National Clinical Research Center for ancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College Institute of Basic Medicine and Cancer (IBMC) Chinese Academy of Sciences Department of clinical trial The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)

In non-small cell lung cancers,the non-squamous and squamous subtypes（nsqNSCLC and sqNSCLC） exhibit disparities in pathophysiology,tumor immunology,and potential genomic correlates affecting responses to immune checkpoint inhibitor（ICI）-based *** our inhouse training cohort（n=85）,the presence of the LRP1B deleterious mutation（LRP1B-del） was associated with longer and shorter progression-free survival（PFS） on ICIs alone in nsqNSCLCs and sqNSCLCs,respectively(Pinteraction=0.008).These results were validated using a larger public ICI cohort(n=208,Pinteractionclinical utility of LRP1B-del in guiding treatment choices for nsqNSCLCs and sqNSCLCs,emphasizing the necessity for a detailed analysis based on pathological subtypes when investigating biomarkers for cancer therapeutics.

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Can patients with mild non-neoplastic lesions diagnosed at baseline screening be safely exempt from surveillance: evidence from multicenter community-based cohorts

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Science China Life Sciences 2025年第1期 263-271页

作者： Siyi He Zhiyi Zhang Guohui Song Zhenhai Wang Chunyun Dai Shipeng Yan Kun Jiang Bingbing Song He Li Maomao Cao Dianqin Sun Fan Yang Xinxin Yan Shaoli Zhang Yi Teng Qianru Li Changfa Xia Wanqing Chen office of Cancer Screening National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College Department of Gastroenterology Gansu Wuwei Tumor Hospital Cixian Cancer Institute Linzhou Cancer Hospital Center for Disease Control and Prevention of Sheyang County Department of Cancer Prevention and Control Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of MedicineCentral South University Luoshan Center for Disease Control and Prevention office for Cancer Control and Research Affiliated Cancer Hospital of Harbin Medical University

Surveillance recommendations for gastric cancer（GC） in current guidelines focused on advanced precancerous lesions and were based on precise diagnosis of severity/extent of baseline lesions. We aimed to develop a less endoscopy-related equipment-dependent risk-stratification tool, and assessed whether mild-precursor-lesion patients can be safely exempt from surveillance. In the multicenter communitybased cohort, 75,051 participants receiving baseline endoscopy were enrolled during 2015–2017 and followed-up until 2021. Cumulative incidence rates（CIRs） of GC for precancerous-conditions were calculated by Kaplan-Meier method and compared by Log-rank tests. Mixedeffects Cox regression models were used to detect potential factors for progression towards GC. A risk score was calculated as counts of selected factors. An independent cohort, including 26,586 participants was used for external validation. During a median follow-up of 6.25 years, CIRs of GC were 0.302%, 0.436%, and 4.756% for normal group, non-neoplastic（atrophic gastritis/intestinal metaplasia） and neoplastic lesions（low-grade/high-grade dysplasia）, respectively(Ptrend<0.001). Four predictors, including male, ≥60 years, smoking, and limited vegetable consumption, were selected for risk-stratification. High-risk patients（≥3 risk factors） with non-neoplastic lesions showed higher GC risks（adjusted HR=7.73, 95%CI: 4.29–13.92）, and their four-year CIR reached the one-year CIR of neoplastic lesions. Further categorizing non-neoplastic lesions by histological grade, both patients with moderate-to-severe lesions（aHR=3.07, 95%CI: 1.67–5.64） and high-risk patients with mild lesions（aHR=7.29, 95%CI: 3.58–14.86） showed higher risks. Consistent trends were observed in validation cohort. High-risk mild-precursor-lesion patients should receive surveillance within 3–5 years after baseline screening. Our study provides evidence on supplementing current guideline recommendations.

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Single-arm trials for domestic oncology drug approvals in China

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Cancer Biology & Medicine 2023年第11期20卷 799-805页

作者： Hong Zhang Sen Liu Chenghao Ge Xiaozhen Liu Yang Liu Chen Yin Yi Li Jing An Zhongtian Yan Xiaoyuan Chen Center for Drug Evaluation National Medical Products AdministrationBeijing 100076China Tsinghua clinical Research Institute(TCRI) School of MedicineTsinghua UniversityBeijing 100084China office of clinical trial Institute Beijing Tsinghua Changgung HospitalBeijing 102218China

The urgent need for effective cancer treatments,particularly for advanced and relapsed cases in which standard therapies are inadequate,has spurred the development of innovative therapeutic drugs1,*** the strategies to expedite drug development,the use of single-arm trials(SATs)is emerging as a promising avenue with substantial potential to shorten drug approval timelines and accelerate market entry.

关键词： drug drugs approval

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Pregabalin induced balance disorder,asthenia,edema,and constipation in an elderly adult:A case report

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World Journal of clinical Cases 2023年第17期11卷 4060-4064页

作者： Li-Ping Ma Cheng Wen Tong-Xiang Zhao Xiang-Ming Jiang Jin Gu office of clinical trial Institution Peking University Shougang HospitalBeijing 100144China Department of Pharmacy Administration and clinical Pharmacy School of Pharmaceutical SciencesPeking UniversityBeijing 100191China Department of Gastrointestinal Surgery Peking University Shougang HospitalBeijing 100144China

BACKGROUND Pregabalin is widely used to treat neuropathic pain associated with postherpetic *** our knowledge,this is the first report on simultaneously occurring dose-related adverse drug reactions(ADRs)of balance disorder,asthenia,peripheral edema,and constipation in an elderly patient after *** SUMMARY A 76-year-old female with a history of postherpetic neuralgia was prescribed pregabalin(300 mg daily).After taking pregabalin for 7 d,the patient developed balance disorder,weakness,peripheral pitting edema(2+),and *** days 8-14,the pregabalin dose was reduced to 150 mg/d based on creatinine *** patient’s peripheral edema improved significantly with the disappearance of all other adverse *** day 15,the pregabalin dose was increased to 225 mg/d to relieve ***,the symptoms mentioned earlier gradually reappeared after 1 wk of pregabalin ***,the complaints were not as severe as when taking 300 mg/d *** patient consulted her pharmacist by telephone and was advised to reduce the dose of pregabalin to 150 mg/d and add acetaminophen(0.5 g,q6h)to relieve *** patient’s ADRs gradually improved over the following *** Older patients should be prescribed a lower initial dose of *** dose should be titrated to the maximum tolerable dose to avoid dose-limiting *** reduction and the addition of acetaminophen may help limit ADR and improve pain control.

关键词： Pregabalin Dose-dependent AEs The elderly population Adverse drug reaction Case report

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Development of a prognostic scoring system for resectable hepatocellular carcinoma

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World Journal of Gastroenterology 2016年第36期22卷 8194-8202页

作者： Carlo Sposito Stefano Di Sandro Federica Brunero Vincenzo Buscemi Carlo Battiston Andrea Lauterio Marco Bongini Luciano De Carlis Vincenzo Mazzaferro Gastrointestinal Surgery and Liver Transplantation Fondazione IRCCS Istituto Nazionale Tumori University of Milan General Surgery and Organ Transplants Ospedale Niguarda Ca’Granda20133 Milan Italy clinical trial office and Biomedical Statistic Fondazione IRCCS Istituto Nazionale Tumori

AIM To develop a prognostic scoring system for overall survival(OS) of patients undergoing liver resection(LR) for hepatocellular carcinoma(HCC).METHODS Consecutive patients who underwent curative LR for HCC between 2000 and 2013 were identified. The series was randomly divided into a training and a validation set. A multivariable Cox model for OS was fitted to the training set. The beta coefficients derived from the Cox model were used to define a prognostic scoring system for OS. The survival stratification was then tested, and the prognostic scoring system was compared with the European Association for the Study of the Liver(EASL)/American Association for the Study of Liver Diseases(AASLD) surgical criteria by means of Harrell's C *** A total of 917 patients were considered. Five variables independently correlated with post-LR survival: Model for End-stage Liver Disease score, hepatitis C virus infection, number of nodules, largest diameter and vascular invasion. Three risk classes were identified, and OS for the three risk classes was significantly different both in the training(P < 0.0001) and the validation set(P = 0.0002). Overall, 69.4% of patients were in the low-risk class, whereas only 37.8% were eligible to surgery according to EASL/AASLD. Survival of patients in the low-risk class was not significantly different compared with surgical indication for EASL/AASLD guidelines(77.2 mo vs 82.5 mo respectively, P = 0.22). Comparison of Harrell's C statistics revealed no significant difference in predictive power between the two systems(-0.00999, P = 0.667).CONCLUSION This study established a new prognostic scoring system that may stratify HCC patients suitable for surgery, expanding surgical eligibility with respect to EASL/AASLD criteria with no harm on survival.

关键词： Hepatocellular carcinoma Liver resection Liver cirrhosis Prognosis Survival study

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Comprehensive characterization of cell disulfidptosis in human cancers:An integrated pan-cancer analysis

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Genes & Diseases 2024年第4期11卷 5-8页

作者： Guo Zhao Yale Jiang Yuning Wang Shuhang Wang Ning Li clinical trial Center National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Excessive accumulation of disulfide molecules,like cystine,can induce disulfide stress and high toxicity in cells,but the reduced form of nicotinamide adenine dinucleotide phosphate can reverse this process and mitiga... 详细信息

关键词： disulfide cancer characterization

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Rare tumors: a blue ocean of investigation

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Frontiers of Medicine 2023年第2期17卷 220-230页

作者： Shuhang Wang Peiwen Ma Ning Jiang Yale Jiang Yue Yu Yuan Fang Huilei Miao Huiyao Huang Qiyu Tang Dandan Cui Hong Fang Huishan Zhang Qi Fan Yuning Wang Gang Liu Zicheng Yu Qi Lei Ning Li clinical trial Center National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Phase I clinical trial Center Fujian Medical University Cancer Hospital/Fujian Cancer HospitalFuzhou 350014China Key Laboratory of Molecular Epigenetics of the Ministry of Education Northeast Normal UniversityChangchun 130024China GenePlus-Shenzhen Shenzhen 518118China

Advances in novel drugs,therapies,and genetic techniques have revolutionized the diagnosis and treatment of cancers,substantially improving cancer patients’*** rare tumors account for a non-negligible number,the practice of precision medicine and development of novel therapies are largely hampered by many *** low incidence and drastic regional disparities result in the difficulty of informative evidence-based diagnosis and *** exhaustion due to difficulty in diagnosis also leads to a lack of recommended therapeutic strategies in clinical guidelines,insufficient biomarkers for prognosis/efficacy,and inability to identify potential novel therapies in clinical ***,by reviewing the epidemiological data of Chinese solid tumors and publications defining rare tumors in other areas,we proposed a definition of rare tumor in China,including 515 tumor types with incidences of less than 2.5/100000 per *** also summarized the current diagnosis process,treatment recommendations,and global developmental progress of targeted drugs and immunotherapy agents on the status ***,we pinpointed the current recommendation chance for patients with rare tumors to be involved in a clinical trial by *** this informative report,we aimed to raise awareness on the importance of rare tumor investigations and guarantee a bright future for rare tumor patients.

关键词： rare tumors diagnosis flowchart treatment strategy clinical trials recommendation

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Bioequivalence of two esomeprazole magnesium enteric-coated formulations in healthy Chinese subjects

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World Journal of clinical Cases 2020年第22期8卷 5518-5528页

作者： Zheng-Zhi Liu Qing Ren Yan-Nan Zhou Hai-Miao Yang Phase I clinical trial Laboratory Affiliated Hospital of Changchun University of Chinese MedicineChangchun 130021Jilin ProvinceChina

BACKGROUND The pharmacokinetics and bioequivalence of esomeprazole in healthy Chinese subjects and the effects of food on the pharmacokinetics have not been well *** To evaluate the pharmacokinetic characteristics of esomeprazole magnesium(Eso)enteric-coated capsule in the healthy subjects in China and the bioequivalence of the two *** This study was conducted in the Phase I clinical trial Unit of the Affiliated Hospital of Changchun University of Chinese Medicine.A total of 64 healthy subjects were enrolled in the ***-two subjects fasted or fed,took the test or reference formulation Eso enteric-coated capsule by a four-cycle,two-sequence crossover of fasting/fed,self-controlled *** liquid chromatographymass spectrometry was performed to determine the drug plasma concentration at 16 different time points within 12 h after drug *** pharmacokinetic parameters Cmax,area under the curve(AUC)0-t,and AUC0-inf were calculated to evaluate the *** Pharmacokinetic parameters were evaluated after subjects took the test formulation and control formulation under fasting *** ratio of geometric means of Cmax was 104.15%,with a confidence interval(CI)of 98.20-110.46%.The ratio of geometric means of AUC0-t was 105.26%,with a CI of 99.80-111.01%.The ratio of geometric means of AUC0-inf was 105.37%,with a CI of 99.97-111.06%.The pharmacokinetic parameters were also evaluated after subjects took the reference formulation of Eso enteric-coated capsule after *** upper limit of 95%CI of the geometric mean ratio of pharmacokinetic parameters of Eso enteric-coated capsules in the postprandial state Cmax was-0.1689,and the point estimate was 0.9509(0.80-1.25).The upper limit of 95%CI of the geometric mean ratio of pharmacokinetic parameters of Eso enteric-coated capsules in the postprandial state AUC0-t was-0.1015(≤0),and the point estimate was 0.9003(0.80-1.25).The upper limit of 95%CI of the geometric

关键词： Esomeprazole Proton pump inhibitor Bioequivalence Pharmacodynamics Gastroesophageal reflux disease

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