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Targeted drug approvals in 2023:breakthroughs by the FDA and NMPA

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Signal Transduction and Targeted Therapy 2024年第3期9卷 813-821页

作者： Lang Zheng Wenjing Wang Qiu Sun Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China West China Medical Publishers West China HospitalSichuan UniversityChengdu 610041China

According to the official website of China’s National Medicines and Pharmaceutical Administration(NMPA),a total of 87 novel drugs were approved in China in 2023,with targeted drugs accounting for 67.8%of the total,amounting to 59 drugs(Fig.1a;Table 1)[https://***/yaopin/ypjgdt/***].Notably,domestic innovation is flourishing,with five first-in-class drugs,including Glumetinib,a c-Met inhibitor from Haihe Biopharma;Leritrelvir,a 3CL protease inhibitor from Raynovent;Anaprazole,a proton pump inhibitor from Xuanzhu Biopharm;Pegol-Sihematide,an EPO drug from Hansoh Pharma;and Zuberitamab from BioRay Biopharmaceutical Co.,***,the world’s first allosteric inhibitor targeting TYK2,Sotyktu(deucravacitinib),has been approved for the treatment of psoriasis and Selumetinib,a MEK inhibitor co-developed by AstraZeneca and Merck Sharp&Dohme(MSD),became the first approved drug in China for the treatment of neurofibromatosis type I(NF1).Beyond these drugs,the approval of novel drug types such as CAR-T cell products,siRNA,monoclonal antibodies,dual antibodies,and ADCs in China is a significant development in the country’s pharmaceutical industry(Fig.1a).

关键词： drugs Merck approval

A novel predictor of unsustained return of spontaneous circulation in cardiac arrest patients through a combination of capnography and pulse oximetry: a multicenter observational study

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World Journal of Emergency Medicine 2024年第1期15卷 16-22页

作者： Jing Yang Hanqi Tang Shihuan Shao Feng Xu Yangyang Fu Shengyong Xu Chen Li Yan Li Yang Liu Joseph Harold Walline Huadong Zhu Yuguo Chen Xuezhong Yu Jun Xu Emergency Department State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100730China Emergency Department Peking University People’s HospitalBeijing 100044China Department of Emergency and Chest Pain Center Shandong Provincial Clinical Research Center for Emergency and Critical Care MedicineKey Laboratory of Emergency and Critical Care Medicine of Shandong ProvinceQilu Hospital of Shandong UniversityJinan 250012China Emergency Department Beijing Jishuitan HospitalBeijing 100035China Emergency Department Tianjin Medical University General HospitalTianjin 300052China Department of Emergency Medicine Penn State Health Milton S.Hershey Medical Center and Penn State College of MedicineHershey 17033USA

BACKGROUND:Unsustained return of spontaneous circulation(ROSC)is a critical barrier to survival in cardiac arrest *** study examined whether end-tidal carbon dioxide(ETCO_(2))and pulse oximetry photoplethysmogram(POP)parameters can be used to identify unsustained ***:We conducted a multicenter observational prospective cohort study of consecutive patients with cardiac arrest from 2013 to ***’general information,ETCO_(2),and POP parameters were collected and statistically ***:The included 105 ROSC episodes(from 80 cardiac arrest patients)comprised 51 sustained ROSC episodes and 54 unsustained ROSC *** 24-hour survival rate was significantly higher in the sustained ROSC group than in the unsustained ROSC group(29.2%vs.9.4%,P<0.05).The logistic regression analysis showed that the difference between after and before ROSC in ETCO_(2)(ΔETCO_(2))and the difference between after and before ROCS in area under the curve of POP(ΔAUCp)were independently associated with sustained ROSC(odds ratio[OR]=0.931,95%confi dence interval[95%CI]0.881-0.984,P=0.011 and OR=0.998,95%CI 0.997-0.999,P<0.001).The area under the receiver operating characteristic curve ofΔETCO_(2),ΔAUCp,and the combination of both to predict unsustained ROSC were 0.752(95%CI 0.660-0.844),0.883(95%CI 0.818-0.948),and 0.902(95%CI 0.842-0.962),***:Patients with unsustained ROSC have a poor *** combination ofΔETCO_(2) andΔAUCp showed signifi cant predictive value for unsustained ROSC.

关键词： Return of spontaneous circulation Pulse oximetry photoplethysmogram End-tidal carbon dioxide Cardiac arrest Cardiopulmonary resuscitation

Pancreatic β-cell failure,clinical implications,and therapeutic strategies in type 2 diabetes

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Chinese Medical Journal 2024年第7期137卷 791-805页

作者： Daxin Cui Xingrong Feng Siman Lei Hongmei Zhang Wanxin Hu Shanshan Yang Xiaoqian Yu Zhiguang Su Molecular Medicine Research Center and Department of Endocrinology and Metabolism West China HospitalSichuan UniversityChengduSichuan 610041China state Key Laboratory of Biotherapy West China HospitalSichuan UniversityChengduSichuan 610041China Clinical Translational Innovation Center West China HospitalSichuan UniversityChengduSichuan 610041China

Pancreaticβ-cell failure due to a reduction in function and mass has been defined as a primary contributor to the progression of type 2 diabetes(T2D).Reserving insulin-producingβ-cells and hence restoring insulin production are gaining attention in translational diabetes research,andβ-cell replenishment has been the main focus for diabetes *** findings inβ-cell proliferation,transdifferentiation,pluripotent stem cell differentiation,and associated small molecules have served as promising strategies to regenerateβ-*** this review,we summarize current knowledge on the mechanisms implicated inβ-cell dynamic processes under physiological and diabetic conditions,in which genetic factors,age-related alterations,metabolic stresses,and compromised identity are critical factors contributing toβ-cell failure in *** article also focuses on recent advances in therapeutic strategies for diabetes treatment by promotingβ-cell proliferation,inducing non-β-cell transdifferentiation,and reprograming stem cell *** a significant challenge remains for each of these strategies,the recognition of the mechanisms responsible forβ-cell development and mature endocrine cell plasticity and remarkable advances in the generation of exogenousβ-cells from stem cells and single-cell studies pave the way for developing potential approaches to cure diabetes.

关键词： Pancreaticβ-cell regeneration Diabetes Insulin Dedifferentiation Transdifferentiation Stem cell

Pericytes protect rats and mice from sepsis-induced injuries by maintaining vascular reactivity and barrier function:implication of miRNAs and microvesicles

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Military Medical Research 2024年第1期11卷 1-18页

作者： Zi-Sen Zhang Yi-Yan Liu Shuang-Shuang He Dai-Qin Bao Hong-Chen Wang Jie Zhang Xiao-Yong Peng Jia-Tao Zang Yu Zhu Yue Wu Qing-Hui Li Tao Li Liang-Ming Liu state Key Laboratory of Trauma Burns and Combined InjuryDepartment of Shock and TransfusionResearch Institute of SurgeryDaping HospitalArmy Medical UniversityChongqing 400042China

Background Vascular hyporeactivity and leakage are key pathophysiologic features that produce multi-organ damage upon *** hypothesized that pericytes,a group of pluripotent cells that maintain vascular integrity and tension,are protective against sepsis via regulating vascular reactivity and *** We conducted a series of in vivo experiments using wild-type(WT),platelet-derived growth factor receptor-β(PDGFR-β)-Cre+mT/mG transgenic mice and Tie2-Cre+Cx43^(flox/flox)mice to examine the relative contribution of pericytes in sepsis,either induced by cecal ligation and puncture(CLP)or lipopolysaccharide(LPS)*** a separate set of experiments with Sprague-Dawley(SD)rats,pericytes were depleted using CP-673451,a selective PDGFR-βinhibitor,at a dosage of 40 mg/(kg·d)for 7 consecutive *** pericytes,vascular endothelial cells(VECs)and vascular smooth muscle cells(VSMCs)were used for mechanistic *** effects of pericytes and pericyte-derived microvesicles(PCMVs)and candidate miRNAs on vascular reactivity and barrier function were also *** CLP and LPS induced severe injury/loss of pericytes,vascular hyporeactivity and leakage(P<0.05).Transplantation with exogenous pericytes protected vascular reactivity and barrier function via microvessel colonization(P<0.05).Cx43 knockout in either pericytes or VECs reduced pericyte colonization in microvessels(P<0.05).Additionally,PCMVs transferred miR-145 and miR-132 to VSMCs and VECs,respectively,exerting a protective effect on vascular reactivity and barrier function after sepsis(P<0.05).miR-145 primarily improved the contractile response of VSMCs by activating the sphingosine kinase 2(Sphk2)/sphingosine-1-phosphate receptor(S1PR)1/phosphorylation of myosin light chain 20 pathway,whereas miR-132 effectively improved the barrier function of VECs by activating the Sphk2/S1PR2/zonula occludens-1 and vascular endothelial-cadherin *** Pericytes are protective a

关键词： Pericyte Vascular reactivity Vascular permeability Cx43 Microvesicle

Smoking of Carica papaya in Nigeria:The rationale,the public health effects and policies for intervention

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Asian Pacific Journal of Tropical Medicine 2024年第3期17卷 95-96页

作者： Abolaji Paul Adekeye Mental Health Department Federal Teaching HospitalIdo-EkitiEkiti StateNigeria Mental Health Department Afe Babalola UniversityAdo-EkitiEkiti StateNigeria

Psychoactive substance use is characterized by the habitual use of substances that have significant effects in altering the activities of neurotransmitters in certain regions of the ***,these alterations manifest as c... 详细信息

关键词： rational behaviour emotional

Genetically predicted waist circumference and risk of atrial fibrillation

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Chinese Medical Journal 2024年第1期137卷 82-86页

作者： Wenting Wang Jiang-shan Tan Jingyang Wang Wei Xu Liting Bai Yu Jin Peng Gao Peiyao Zhang Yixuan Li Yanmin Yang Jinping Liu Department of Cardiopulmonary Bypass State Key Laboratory of Cardiovascular DiseaseFuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China Department of Anaesthesiology Second Affiliated HospitalHainan Medical CollegeHaikouHainan 570311China state Key Laboratory of Cardiovascular Disease Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China

Introduction:Observational studies have revealed an association between waist circumference(WC)and atrial fibrillation(AF).However,it is difficult to infer a causal relationship from observational studies because the observed associations could be confounded by unknown risk ***,the causal role of WC in AF is *** study was designed to investigate the causal association between WC and AF using a two-sample Mendelian randomization(MR)***:In our two-sample MR analysis,the genetic variation used as an instrumental variable for MR was acquired from a genome-wide association study(GWAS)of WC(42 single nucleotide polymorphisms with a genetic significance of P<5×10^(-8)).The data of WC(from the Genetic Investigation of ANthropometric Traits consortium,containing 232,101 participants)and the data of AF(from the European Bioinformatics Institute database,containing 55,114 AF cases and 482,295 controls)were used to assess the causal role of WC on *** different approaches(inverse variance weighted[IVW],MR-Egger,and weighted median regression)were used to ensure that our results more ***:All three MR analyses provided evidence of a positive causal association between high WC and *** WC was suggested to increase the risk of AF based on the IVW method(odds ratio[OR]=1.43,95%confidence interval[CI],1.30-1.58,P=2.51×10^(-13)).The results of MR-Egger and weighted median regression exhibited similar trends(MR-Egger OR=1.40[95%CI,1.08-1.81],P=1.61×10^(-2);weighted median OR=1.39[95%CI,1.21-1.61],P=1.62×10^(-6)).MR-Egger intercepts and funnel plots showed no directional pleiotropic effects between high WC and ***:Our findings suggest that greater WC is associated with an increased risk of *** measures to reduce WC may help prevent the occurrence of AF.

关键词： Genetically predicted Waist circumference Atrial fibrillation Mendelian randomization

Early-onset and later-onset cancer: trends, risk factors, and prevention in Northern China

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Science China Life Sciences 2024年第9期67卷 1928-1940页

作者： Tong Liu Chen-An Liu Qing-Song Zhang Qi Zhang Yi-Ming Wang Meng-Meng Song Shi-Qi Lin Li Deng Shou-Ling Wu Han-Ping Shi Department of Gastrointestinal Surgery Department of Clinical Nutrition Beijing Shijitan Hospital Capital Medical University National Clinical Research Center for Geriatric Diseases Xuanwu Hospital Capital Medical University Key Laboratory of Cancer FSMP for state Market Regulation Laboratory for Clinical Medicine Capital Medical University Department of General Surgery Kailuan General Hospital Department of Genetics Yale School of Medicine Department of Hepatobiliary Surgery Kailuan General Hospital Cardiovascular Research Institute University of California Department of Cardiology Kailuan General Hospital

The characteristics of early-onset(onset age <50 years) and later-onset(onset age ≥50 years) cancers differ significantly. Identifying novel risk factors for both types of cancer is crucial for increasing awareness of cancer prevention and for reducing its burden. This study aimed to analyze the trends in incidence and risk factors for early-onset and late-onset cancers. We conducted a prospective study by drawing data from the Kailuan Study. This study included 6,741 participants with cancer(624 with early-onset cancer and 6,117 with later-onset cancer)and 6,780 matched controls among the 186,249 participants who underwent Kailuan health examinations from 2006 to 2019. The primary outcomes were cancer incidence rates, and associated risk factors for early-and later-onset cancer. Weighted Cox regression was used to calculate hazard ratios and 95% confidence intervals of each exposure factor for early-and later-onset cancer by cancer type. Populationattributable risk proportions were used to estimate the number of cases that could be prevented by eliminating a risk factor from the population. Except for liver cancer, incidence rates for nearly all types of cancer increased during the study period. Smoking, alcohol consumption, lipid metabolism disorders, hypertension, diabetes mellitus, fatty liver, and inflammation were associated with a significantly increased risk of cancer at multiple sites, but risk factors for cancer incidence differed by site. Smoking, alcohol consumption, inflammation,and hypertension were the major contributors to preventable cancer. The incidence of several different types of cancer, including earlyonset cancer, is increasing in northeastern China. Differences in risk factors between early-onset and later-onset malignancies may contribute to the divergence in the observed changes in incidence trends between these two specific types of cancer.

关键词： cancer early-onset later-onset trend risk factor prevention

Morphometric Study of the Mastoid Process and its Role in Sex Differentiation:A Nigerian Computed Tomography Study

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Journal of Forensic Science and Medicine 2024年第1期10卷 1-10页

作者： Beryl Shitandi Ominde John NIgabari Joyce Ekeme Ikubor Department of Human Anatomy and Cell Biology Delta State UniversityAbrakaNigeria Department of Mathematics Delta State UniversityAbrakaNigeria Department of Radiology Delta State University Teaching HospitalOgharaNigeria

Background:The mastoid process can be utilized in forensic identification due to its resistance to alterations and population variations in its *** study investigated the role of mastoid parameters in the determination of sex in a Nigerian *** and Objectives:The aim of this study was to determine the gender differences in measurements of the mastoid ***,the study aimed at assessing the percentage accuracy of using the mastoid variables in sex *** and Methods:This cross-sectional study used computed tomographic images of the brain,stored in the radiology unit of a referral hospital in Delta state,*** was granted by the hospital’s Ethics *** measurements of the mastoid process were taken on images of 310 patients(170 males and 140 females)aged 20-80 *** were summarized using means and standard ***,side,and age group comparisons were assessed using the independent t-test,paired t-test,and analysis of variance,*** association between variables was probed using Pearson’s correlation *** discriminant function analysis was used to determine the accuracy of correct sex *** probability value was set atstate,Nigeria.

关键词： Forensic mastoid process measurements sex determination

Association of stage 1 hypertension defined by the 2017 ACC/AHA guideline with cardiovascular events and mortality in Chinese adults

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Chinese Medical Journal 2024年第1期137卷 63-72页

作者： Qiannan Gao Liuxin Li Jingjing Bai Luyun Fan Jiangshan Tan Shouling Wu Jun Cai Hypertension Center Fuwai HospitalState Key Laboratory of Cardiovascular DiseaseNational Center for Cardiovascular DiseasesPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing 100037China Department of Cardiology Kailuan General HospitalNorth China University of Science and TechnologyTangshanHebei 063000China Emergency Center Fuwai HospitalState Key Laboratory of Cardiovascular DiseaseNational Center for Cardiovascular DiseasesPeking Union Medical CollegeChinese Academy of Medical SciencesBeijing 100037China

Background:The 2017 American College of Cardiology/American Heart Association(ACC/AHA)blood pressure(BP)guideline lowered the threshold defining hypertension to 130/80 ***,how stage 1 hypertension defined using this guideline is associated with cardiovascular events in Chinese adults remains *** study assessed the association between stage 1 hypertension defined by the 2017 ACC/AHA guideline and clinical outcomes in the Chinese ***:Participants with stage 1 hypertension(n=69,509)or normal BP(n=34,142)were followed in this study from 2006/2007 to *** 1 hypertension was defined as a systolic blood pressure of 130-139 mmHg or a diastolic blood pressure of 80-89 *** were taking antihypertensive medication or had a history of myocardial infarction(MI),stroke,or cancer at *** primary outcome was a composite of MI,stroke,and all-cause *** secondary outcomes were individual components of the primary *** proportional hazards models were used for the ***:During a median follow-up of 11.09 years,we observed 10,479 events(MI,n=995;stroke,n=3408;all-cause mortality,n=7094).After multivariable adjustment,the hazard ratios for stage 1 hypertension *** BP were 1.20(95%confidence interval[CI],1.13-1.25)for primary outcome,1.24(95%CI,1.05-1.46)for MI,1.45(95%CI,1.33-1.59)for stroke,and 1.11(95%CI,1.04-1.17)for all-cause *** hazard ratios for participants with stage 1 hypertension who were prescribed antihypertensive medications compared with those without antihypertensive treatment during the follow-up was 0.90(95%CI,0.85-0.96).Conclusions:Using the new definition,Chinese adults with untreated stage 1 hypertension are at higher risk for MI,stroke,and all-cause *** finding may help to validate the new BP classification system in China.

关键词： Hypertension Cardiovascular disease All-cause mortality Cox regression analysis