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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/index.html].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.,Ltd.Additionally,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

Investigating the elliptic anisotropy of identified particles in p-Pb collisions with a multi-phase transport model

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Nuclear Science and Techniques 2024年第2期35卷 160-169页

作者： si-Yu Tang Liang zheng Xiao-Ming Zhang Ren-Zhuo Wan School of Mathematical and Physical Sciences Wuhan Textile UniversityWuhan 430200China School of Mathematics and Physics China University of Geosciences(Wuhan)Wuhan 430074China Key Laboratory of Quark and Lepton Physics(MOE)and Institute of Particle Physics Central China Normal UniversityWuhan 430079China Hubei Key Laboratory of Digital Textile Equipment Wuhan Textile UniversityWuhan 430200China School of Electronic and Electrical Engineering Wuhan Textile UniversityWuhan 430200China

The elliptic azimuthal anisotropy coefficient(v_(2))of the identified particles at midrapidity(|η|<0.8)was investigated in p-Pb collisions at√s_(NN)=5.02 TeV using a multi-phase transport model(AMPT).The calculatio... 详细信息

The elliptic azimuthal anisotropy coefficient(v_(2))of the identified particles at midrapidity(|η|sions at√s_(NN)=5.02 TeV using a multi-phase transport model(AMPT).The calculations of differential v_(2)based on the advanced flow extraction method of light flavor hadrons(pions,kaons,protons,andΛ)in small collision systems were extended to a wider transverse momentum(p_(T))range of up to 8 GeV/c for the first time.The string-melting version of the AMPT model provides a good description of the measured p_(T)-differential v_(2)of the mesons but exhibits a slight deviation from the baryon v_(2).In addition,we observed the features of mass ordering at low p_(T)and the approximate number-of-constituentquark(NCQ)scaling at intermediate p_(T).Moreover,we demonstrate that hadronic rescattering does not have a significant impact on v_(2)in p-Pb collisions for different centrality selections,whereas partonic scattering dominates in generating the elliptic anisotropy of the final particles.This study provides further insight into the origin of collective-like behavior in small collision systems and has referential value for future measurements of azimuthal anisotropy.

关键词： Azimuthal anisotropy Small collision systems Transport model

Shengmaisan combined with Liuwei Dihuang Decoction alleviates chronic intermittent hypoxia-induced cognitive impairment by activating the EPO/EPOR/JAK2 signaling pathway

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Chinese Journal of Natural Medicines 2024年第5期22卷 426-440页

作者： si Jianchao CHEN Xue QI Kerong LI Dongli LIU Bingbing zheng Yuying JI Ensheng YANG Shengchang Department of Physiology Hebei University of Chinese MedicineShijiazhuang 050000China Hebei Technology Innovation Center of TCM Combined Hydrogen Medicine Shijiazhuang 050000China Department of Geriatrics First People’s Hospital of XiaoganXiaogan 432000China

Chronic intermittent hypoxia(CIH),a principal pathophysiological aspect of obstructive sleep apnea(OSA),is associated with cognitive deficits.Clinical evidence suggests that a combination of Shengmaisan and Liuwei Dihuang Decoctions(SMS-LD)can enhance cognitive function by nourishing yin and strengthening the kidneys.This study aimed to assess the efficacy and underlying mechanisms of SMS-LD in addressing cognitive impairments induced by CIH.We exposed C57BL/6N mice to CIH for five weeks(20%-5%O_(2),5 min/cycle,8 h/day)and administered SMS-LD intragastrically(15.0 or 30 g·kg^(-1)·day)30 min before each CIH session.Additionally,AG490,a JJanus kinase 2(JAK2)inhibitor,was administered via intracerebroventricular injection.Cognitive function was evaluated using the Morris water maze,while synaptic and mitochondrial structures were examined by transmission electron microscopy.Oxidative stress levels were determined using DHE staining,and the activation of the erythropoietin(ER)/ER receptor(EPOR)/JAK2 signaling pathway was analyzed through immunohistochemistry and Western blotting.To further investigate molecular mechanisms,HT22 cells were treated in vitro with either SMS-LD medicated serum alone or in combination with AG490 and then exposed to CIH for 48 h.Our results indicate that SMS-LD significantly mitigated CIH-induced cognitive impairments in mice.Specifically,SMS-LD treatment enhanced dendritic spine density,ameliorated mitochondrial dysfunction,reduced oxidative stress,and activated the EPO/EPOR/JAK2 signaling pathway.Conversely,AG490 negated SMS-LD’s neuroprotective and cognitive improvement effects under CIH conditions.These findings suggest that SMS-LD’s beneficial impact on cognitive impairment and synaptic and mitochondrial integrity under CIH conditions may predominantly be attributed to the activation of the EPO/EPOR/JAK2 signaling pathway.

关键词： Chronic intermittent hypoxia Cognitive impairment Shengmaisan Liuwei Dihuang Decoction Oxidative stress EPO/EPOR/JAK2 signaling pathway

Predictors of complications after prophylactic ileostomy reversal for rectal cancer:A retrospective study

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World Journal of Gastrointestinal Surgery 2024年第5期16卷 1354-1362页

作者： Quan Lv Xin-Peng Shu Dong Peng si-Qi Li zheng Xiang Department of Gastrointestinal Surgery The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Chongqing Key Laboratory of Department of General Surgery The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China

BACKGROUND Previous studies have analyzed the risk factors for complications after ileostomy reversal for rectal cancer(RC),but there were significant differences in the reported risk factors for complications after stoma reversal.No studies have analyzed the risk factors for stoma-related complications and overall postoperative com-plications separately.AIM To analyze the risk factors for overall complications and stoma-related complications after ileostomy reversal for patients with RC.METHODS This was a retrospective study of 439 patients who underwent ileostomy reversal at a clinical center and were followed up between September 2012 and September 2022.Continuous variables are expressed as the mean±SD and were analyzed with independent-sample t tests,while frequency variables are expressed as n(%),and theχ2 test or Fisher’s exact test was used.Univariate and multivariate logistic regression analyses were used to identify predictors of overall complications and stoma-related complications.RESULTS The overall complication rate after ileostomy reversal was 11.4%.Patients with lower preoperative albumin concentration(Psis of the study showed that a higher body mass index(BMI)(Psion(P=0.049),time from primary surgery to ileostomy reversal(Psion analysis revealed that a lower preoperative albumin level(Psis revealed that BMI(PsiON The pre

关键词： Ileostomy Reversal Risk factors Complications Rectal cancer

Identification and Expression Profile of a Neuropeptide LFRFamide-Like Gene During Different Stages of Gonadal Development in the Cephalopod Sepia pharaonis

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Journal of Ocean University of China 2024年第2期23卷 499-508页

作者： qiu Jiayin SUN Lianlian LI Shuang ZHOU Xu CHI Changfeng zheng Libing National and Provincial Joint Engineering Research Center for Marine Germplasm Resources Exploration and Utilization School of Marine Science and TechnologyZhejiang Ocean UniversityZhoushan 316022China

Neuropeptides are widely distributed in vertebrates and invertebrates,regulating a variety of physiological activities in the organisms,such as metabolism,feeding and reproduction.In this study,to explore the function of neuropeptide LFRFamide in Sepia pharaonis,the full-length cDNA of LFRFamide-like gene(named SpLFRFL,MG869822.1)was identified with rapid amplification of cDNA ends(RACE)method.The sequence of SpLFRFL was 860 bp in length and encoded 188 amino acids containing 4 different mature peptides:1 copy of PHTPFRFamide,NSLFRFamide,TIFRFamide,and 3 copies of GNLFRFamide.Multiple alignment and phylogenetic analysis results showed that SpLFRFL shared high identity with LFRFamides of Sepia officinalis and Sepiella japonica and had the closest relationship with them.Through quantitative Real-time PCR(qRT-PCR),it was found that the SpLFRFL gene was highly expressed in the optic lobe and brain at three different stages during gonad development in both genders.Moreover,the four mature peptides at a concentration of 0.01μmol L^(−1) could inhibit the protein synthesis in the Chinese hamster ovary cell strain-K1(CHOK1)induced by SpGnRH.These data suggest that SpLFRFL might be involved in the development and reproduction of S.pharaonis.The results can contribute to future studies on neuropeptide evolution and function and benefit the cuttlefish farming.

关键词： neuropeptide LFRFamide-like cephalopod cuttlefish Sepia pharaonis development reproduction

Train-induced aerodynamic characteristics of vertical sound barriers influenced by several factors

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Railway Engineering Science 2024年第2期32卷 177-193页

作者： Xiaowei qiu Xiaozhen Li Jing zheng Ming Wang State Key Laboratory of Bridge Intelligent and Green Construction Southwest Jiaotong UniversityChengdu 611756SichuanChina Wind Engineering Key Laboratory of sichuan Province Southwest Jiaotong UniversityChengdu 611756SichuanChina School of Architecture and Civil Engineering West Anhui UniversityLu’anAnhuiChina

Investigations into the aerodynamic properties of vertical sound barriers exposed to high-speed operations employ computational fluid dynamics.The primary focus of this research is to evaluate the influence of train speed and the distance(D)from the track centerline under various operating conditions.The findings elucidate a marked elevation in the aerodynamic effect amplitude on sound barriers as train speeds increase.In single-train passages,the aerodynamic effect amplitude manifests a direct relationship with the square of the train speed.When two trains pass each other,the aerodynamic amplitude intensifies due to an additional aerodynamic increment on the sound barrier.This increment exhibits an approximate quadratic correlation with the retrograde train speed.Notably,the impact of high-speed trains on sound barrier aerodynamics surpasses that of low-speed trains,and this discrepancy amplifies with larger speed differentials between trains.Moreover,the train-induced aerodynamic effect diminishes significantly with greater distance(D),with occurrences of pressure coefficient(CP)exceeding the standard thresholds during dual-train passages.This study culminates in the formulation of universal equations for quantifying the influence of train speed and distance(D)on sound barrier aerodynamic characteristics across various operational scenarios.

关键词： Aerodynamic characteristic Sound barrier Two trains passing each other Distance from track centerline CFD simulation

Understanding livelihood vulnerability:a perspective from Western sichuan’s ethnic rural settings

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Journal of Mountain Science 2024年第2期21卷 380-396页

作者： YU Yongqian JING zheng WANG Yan qiu Xiaoping YANG Xueting XU Yun School of Geography and Resource Science Sichuan Normal UniversityChengdu 610101China Key Laboratory of land Resources Evaluation and Monitoring in Southwest Ministry of EducationSichuan Normal UniversityChengdu 610101China sichuan County Economic Development Research Center Mianyang Normal UniversityMianyang 621000China Institute of Mountain Hazards and Environment Chinese Academy of SciencesChengdu 610041China

To explore the livelihood status and key influencing factors of rural households in the minority areas,we collected flat data from 284 rural households in 32 villages across 12 counties of Western sichuan from 2021 to 2022.We conducted participatory household survey on the livelihood status of the rural households and try to identify the key factors to influence their livelihood vulnerability using multiple linear regression.The results showed that:the livelihood situation of the rural households is relatively vulnerable.The vulnerability varies significantly with the income levels,education levels,and income sources.The vulnerability of farm households,categorized from low to high livelihood types,follows the sequence:non-agricultural dominant households,non-agricultural households,agricultural dominant households,and pure agricultural households.The degree of damage to the natural environment,education costs,loan opportunities,the proportion of agricultural income to annual household income,and the presence of sick people in the household have significant positive effects on the livelihood vulnerability index(LVI)of rural households;while help from relatives and friends,net income per capita,household size,household education,agricultural land area,participation in industrial organizations,number of livestock,purchase of commercial houses,drinking water source,and self-supply of food have significant negative effects.Based on the findings,we believe that local rural households operate in a complex livelihood system and recommend continuous interventions targeting key influences to provide empirical research support for areas facing similar situations.

关键词： Livelihood Vulnerability Rural households Ethnic areas

Global epidemiology of mental disorder in atrial fibrillation between 1998-2021:A systematic review and meta-analysis

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World Journal of Psychiatry 2024年第1期14卷 179-193页

作者： Shuai Zhang Na Zhang Liu Liu Wang zheng Zi-Lin Ma si-Yu Qiao Ying-Li Zhao Yi-Hong Wei Gang Wu qiu-Ting Yu Bing Deng Lin Shen Department of Cardiology LongHua Hospital Shanghai University of Traditional Chinese MedicineShanghai 200032China Department of Dermatology Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghai 200437China

BACKGROUND As the burden of mental disorders among patients with atrial fibrillation(AF)increases,researchers are beginning to pay close attention to the risk and prevalence of these comorbidities.Although studies have independently analyzed the risk of comorbidity with depression and anxiety in patients with AF,no study has systematically focused on the global epidemiology of these two mental disorders.AIM To explore the prevalence of depression and anxiety in patients with AF.METHODS Five databases were searched from their date of establishment until January 2023.Observational studies reporting the comorbidity of AF with depression and anxiety,were included in this study.Basic information,such as the first author/publication year,study year,study type,and prevalence of depression and anxiety,were extracted.STATA SE 15.1 was used to analyze the data.Subgroup,meta-regression,and sensitivity analyses were performed to estimate study heterogeneity.RESULTS After a thorough search,26 studies were identified and included in this metaanalysis.The prevalence rates of depression and anxiety in adults with AF were 24.3%and 14.5%,respectively.Among adult males with AF,the prevalence was 11.7%and 8.7%,respectively,whereas in females it was 19.8%and 10.1%,respectively.In older adults with AF,the prevalence rates of depression and anxiety were 40.3%and 33.6%,respectively.The highest regional prevalence of depression and anxiety was observed in European(30.2%)and North American(19.8%)patients with AF.CONCLUsiON In this study,we found that the prevalence of depression and anxiety among patients with AF varies with sex,region,and evaluation scales,suggesting the need for psychological interventions for patients with AF in clinical practice.

关键词： Atrial fibrillation Depression Anxiety Prevalence

Nature-inspired design of droplet-synthesized polymeric nanoelectrode for photoelectrochemical microRNA sensing within single cells

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Science Bulletin 2024年第2期69卷 159-162页

作者： si-Yuan Yu Yi-Li Liu zheng Li Dechen Jiang Jing-Juan Xu Hong-Yuan Chen Wei-Wei Zhao State Key Laboratory of Analytical Chemistry for Life Science School of Chemistry and Chemical EngineeringNanjing UniversityNanjing 210023China

Nanoelectrodes have been shown to be powerful tools for nanoscopic research on single entities,deepening the understanding of heterogeneity and stochastics for single molecules,nanoparticles and cells[1–3].However,despite their importance,current nanoelectrode preparations are highly restrained to flame/electrochemical etching,metal sputtering,electrochemical deposition,etc.[3],resulting in a limited range of materials(mainly gold,platinum and carbon)for potential-resolved detection of redox-active species(Table S1 online).The enrichment of preparation methods to introduce novel materials and mechanisms should prove significant for the development of nanoelectrodes.

关键词： electrode deepening restrained