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Journal of Pharmaceutical Analysis 2024年第6期14卷 851-862页

作者： Qianlin Song Chao Song Xin Chen Yunhe Xiong Ziqi He Xiaozhe Su Jiawei Zhou Hu Ke Caitao Dong Wenbiao Liao Sixing Yang department of Urology Renmin Hospital of Wuhan UniversityWuhan430060China department of Obstetrics and Gynecology Renmin Hospital of Wuhan UniversityWuhan430060China

Oxalate is an organic dicarboxylic acid that is a common component of plant *** kidneys are essential organs for oxalate excretion,but excessive oxalates may induce kidney *** microtubule associated homolog 2(JPT2)is a critical molecule in Ca^(2+)mobilization,and its intrinsic mechanism in oxalate exposure and kidney stones remains *** study aimed to reveal the mechanism of JPT2 in oxalate exposure and kidney *** approaches were used to control JPT2 expression in cells and mice,and the JPT2 mechanism of action was analyzed using transcriptomics and untargeted *** results showed that oxalate exposure triggered the upregulation of JPT2,which is involved in nicotinic acid adenine dinucleotide phosphate(NAADP)-mediated Ca^(2+)*** analysis revealed that cell adhesion and macrophage inflammatory polarization were inhibited by JPT2 knockdown,and these were dominated by phosphatidylinositol 3-kinase(PI3K)/AKT signaling,*** metabolomics indicated that JPT2 knockdown inhibited the production of succinic acid semialdehyde(SSA)in ***,JPT2 deficiency in mice inhibited kidney stones *** conclusion,this study demonstrates that oxalate exposure facilitates kidney stones by promoting crystal-cell adhesion,and modulating macrophage metabolism and inflammatory polarization via JPT2/PI3K/AKT signaling.

关键词： Oxalate Kidney stones JPT2 Crystal-cell adhesion Immunoregulation

Ferroptosis and endoplasmic reticulum stress in ischemic stroke

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Neural Regeneration Research 2024年第3期19卷 611-618页

作者： Yina Li Mingyang Li Shi Feng Qingxue Xu Xu Zhang Xiaoxing Xiong Lijuan Gu Central Laboratory Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina department of Anesthesiology Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina department of Neurosurgery Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina

Ferroptosis is a form of non-apoptotic programmed cell death,and its mechanisms mainly involve the accumulation of lipid peroxides,imbalance in the amino acid antioxidant system,and disordered iron *** primary organelle responsible for coordinating external challenges and internal cell demands is the endoplasmic reticulum,and the progression of inflammatory diseases can trigger endoplasmic reticulum *** has suggested that ferroptosis may share pathways or interact with endoplasmic reticulum stress in many diseases and plays a role in cell *** and endoplasmic reticulum stress may occur after ischemic ***,there are few reports on the interactions of ferroptosis and endoplasmic reticulum stress with ischemic *** review summarized the recent research on the relationships between ferroptosis and endoplasmic reticulum stress and ischemic stroke,aiming to provide a reference for developing treatments for ischemic stroke.

关键词： cell death endoplasmic reticulum stress ferroptosis ischemic stroke lipid peroxidation

Vagus nerve stimulation in cerebral stroke:biological mechanisms,therapeutic modalities,clinical applications,and future directions

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Neural Regeneration Research 2024年第8期19卷 1707-1717页

作者： Li Du Xuan He Xiaoxing Xiong Xu Zhang Zhihong Jian Zhenxing Yang department of Anesthesiology Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina department of Neurosurgery Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina

Stroke is a major disorder of the central nervous system that poses a serious threat to human life and quality of *** stro ke victims are left with long-term neurological dysfunction,which adversely affects the well-being of the individual and the broader socioeconomic ***,poststroke brain dysfunction is a major and difficult area of *** nerve stimulation is a Food and Drug Administration-approved exploratory treatment option for autis m,refractory depression,epilepsy,and Alzheimer’s *** is expected to be a novel therapeutic technique for the treatment of stroke owing to its association with multiple mechanisms such as alte ring neurotransmitters and the plasticity of central neuro *** animal models of acute ischemic stroke,vagus nerve stimulation has been shown to reduce infarct size,reduce post-stroke neurological damage,and improve learning and memory capacity in rats with stroke by reducing the inflammatory response,regulating bloodbrain barrier permeability,and promoting angiogenesis and *** present,vagus nerve stimulation includes both invasive and non-invasive vagus nerve *** studies have found that invasive vagus nerve stimulation combined with rehabilitation therapy is effective in im proving upper limb motor and cognitive abilities in stroke *** clinical studies have shown that non-invasive vagus nerve stimulation,including ear/ce rvical vagus nerve stimulation,can stimulate vagal projections to the central nervous system similarly to invasive vagus nerve stimulation and can have the same *** this paper,we first describe the multiple effects of vagus nerve stimulation in stroke,and then discuss in depth its neuroprotective mechanisms in ischemic *** go on to outline the res ults of the current major clinical applications of invasive and non-invasive vagus nerve ***,we provide a more comprehensive evaluation of the advantages and disadvantages of di

关键词： cerebral stroke neuroplasticity non-invasive vagus nerve stimulation rehabilitation vagus nerve stimulation

The action mechanism by which C1q/tumor necrosis factor-related protein-6 alleviates cerebral ischemia/reperfusion injury in diabetic mice

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Neural Regeneration Research 2024年第9期19卷 2019-2026页

作者： Bo Zhao Mei Li Bingyu Li Yanan Li Qianni Shen Jiabao Hou Yang Wu Lijuan Gu Wenwei Gao department of Anesthesiology Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina Central Laboratory Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina department of Critical Care Medicine Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina

Studies have shown that C1q/tumor necrosis factor-related protein-6 (CTRP6) can alleviate renal ischemia/reperfusion injury in mice. However, its role in the brain remains poorly understood. To investigate the role of CTRP6 in cerebral ischemia/reperfusion injury associated with diabetes mellitus, a diabetes mellitus mouse model of cerebral ischemia/reperfusion injury was established by occlusion of the middle cerebral artery. To overexpress CTRP6 in the brain, an adeno-associated virus carrying CTRP6 was injected into the lateral ventricle. The result was that oxygen injury and inflammation in brain tissue were clearly attenuated, and the number of neurons was greatly reduced. In vitro experiments showed that CTRP6 knockout exacerbated oxidative damage, inflammatory reaction, and apoptosis in cerebral cortical neurons in high glucose hypoxia-simulated diabetic cerebral ischemia/reperfusion injury. CTRP6 overexpression enhanced the sirtuin-1 signaling pathway in diabetic brains after ischemia/reperfusion injury. To investigate the mechanism underlying these effects, we examined mice with depletion of brain tissue-specific sirtuin-1. CTRP6-like protection was achieved by activating the sirtuin-1 signaling pathway. Taken together, these results indicate that CTRP6 likely attenuates cerebral ischemia/reperfusion injury through activation of the sirtuin-1 signaling pathway.

关键词： brain C1q/tumor necrosis factor-related protein-6 cerebral apoptosis diabetes inflammation ischemia/reperfusion injury neuron neuroprotection oxidative damage Sirt1

Ferroptosis:a potential therapeutic target for stroke

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Neural Regeneration Research 2024年第5期19卷 988-997页

作者： Chengli Liu Guijun Wang Wenrui Han Qi Tian Mingchang Li department of Neurosurgery Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina

Ferroptosis is a form of regulated cell death characterized by massive iron accumulation and iron-dependent lipid peroxidation,differing from apoptosis,necroptosis,and autophagy in several *** is regarded as a critical mechanism of a series of pathophysiological reactions after stroke because of iron overload caused by hemoglobin degradation and iron metabolism *** this review,we discuss ferroptosis-related metabolisms,important molecules directly or indirectly targeting iron metabolism and lipid peroxidation,and transcriptional regulation of ferroptosis,revealing the role of ferroptosis in the progression of *** present updated progress in the intervention of ferroptosis as therapeutic strategies for stroke in vivo and in vitro and summarize the effects of ferroptosis inhibitors on *** review facilitates further understanding of ferroptosis pathogenesis in stroke,proposes new targets for the treatment of stroke,and suggests that more efforts should be made to investigate the mechanism of ferroptosis in stroke.

关键词： cell death ferroptosis oxidative stress stroke treatment

AGK2 pre-treatment protects against thioacetamide-induced acute liver failure via regulating the MFN2-PERK axis and ferroptosis signaling pathway

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 43-51页

作者： Qing-Qi Zhang Qian Chen Pan Cao Chun-Xia Shi Lu-Yi Zhang Lu-Wen Wang Zuo-Jiong Gong department of Infectious Diseases Renmin Hospital of Wuhan UniversityWuhan 430060China

Background:Acute liver failure(ALF)is an unpredictable and life-threatening critical *** pathological characteristic of ALF is massive necrosis of hepatocytes and lots of inflammatory cells infiltration which may lead to multiple organ ***:Animals were divided into 3 groups,normal,thioacetamide(TAA,ALF model)and TAA+*** L02 cells were divided into 5 groups,normal,TAA,TAA+mitofusin 2(MFN2)-siRNA,TAA+AGK2,and TAA+AGK2+MFN2-siRNA *** liver histology was evaluated with hematoxylin and eosin staining,inositol-requiring enzyme 1(IRE1),activating transcription factor 6β(ATF6β),protein kinase R(PKR)-like endoplasmic reticulum kinase(PERK)and phosphorylated-PERK(p-PERK).C/EBP homologous protein(CHOP),reactive oxygen species(ROS),MFN2 and glutathione peroxidase 4(GPX4)were measured with Western blotting,and cell viability and liver chemistry were also *** endoplasmic reticulum membranes(MAMs)were measured by ***:The liver tissue in the ALF group had massive inflammatory cell infiltration and hepatocytes necrosis,which were reduced by AGK2 *** comparison to the normal group,apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+in the TAA-induced ALF model group were significantly increased,which were decreased by AGK2 *** levels of MFN2 and GPX4 were decreased in TAA-induced mice compared with the normal group,which were enhanced by AGK2 *** with the TAA-induced L02 cell,apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+were further increased and levels of MFN2 and GPX4 were decreased in the MFN2-siRNA ***2 pre-treatment decreased the apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+and enhanced the protein expression of MFN2 and GPX4 in MFN2-siRNA treated L02 *** observation showed that level of MAMs was promoted in the AGK2 pre-treatment group when compared with the TAA-induced gr

关键词： SIRT2 inhibitor AGK2 Acute liver failure MFN2 Ferroptosis

Metabolic and proteostatic differences in quiescent and active neural stem cells

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Neural Regeneration Research 2024年第1期19卷 43-48页

作者： Jiacheng Yu Gang Chen Hua Zhu Yi Zhong Zhenxing Yang Zhihong Jian Xiaoxing Xiong department of Neurosurgery Renmin Hospital of Wuhan UniversityWuhanHubei ProvinceChina

Adult neural stem cells are neurogenesis progenitor cells that play an important role in ***,neural regeneration may be a promising target for treatment of many neurological *** regenerative capacity of adult neural stem cells can be chara cterized by two states:quiescent and *** adult neural stem cells are more stable and guarantee the quantity and quality of the adult neural stem cell *** adult neural stem cells are chara cterized by rapid proliferation and differentiation into neurons which allow for integration into neural *** review focuses on diffe rences between quiescent and active adult neural stem cells in nutrition metabolism and protein ***,we discuss the physiological significance and underlying advantages of these diffe *** to the limited number of adult neural stem cells studies,we refe rred to studies of embryonic adult neural stem cells or non-mammalian adult neural stem cells to evaluate specific mechanisms.

关键词： adult neurogenesis cell metabolic pathway cellular proliferation neural stem cell niches neural stem cells neuronal differentiation nutrient sensing pathway proteostasis

Tildrakizumab for moderate-to-severe plaque psoriasis in Chinese patients:A 12-week randomized placebo-controlled phase III trial with long-term extension

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Chinese Medical Journal 2024年第10期137卷 1190-1198页

作者： Chen Yu Songmei Geng Bin Yang Yunhua Deng Fuqiu Li Xiaojing Kang Mingye Bi Furen Zhang Yi Zhao Weili Pan Zhongwei Tian Jinhua Xu Zhenghua Zhang Nan Yu Xinsuo Duan Shuping Guo Qing Sun Weiquan Li Juan Tao Zhijun Liu Yuanyuan Yin Gang Wang department of dermatology Xijing HospitalThe Fourth Military Medical UniversityXi’anShaanxi 710032China department of dermatology The Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’anShaanxi 710004China department of dermatology Dermatology Hospital of Southern Medical UniversityGuangzhouGuangdong 510091China department of dermatology Tongji HospitalHuazhong University of Science and TechnologyWuhanHubei 430030China department of dermatology The Second Hospital of Jilin UniversityChangchunJilin 130041China department of dermatology People’s Hospital of Xinjiang Uygur Autonomous RegionUrumqiXinjiang 830001China department of dermatology Wuxi People’s Hospital of Wuxi CityWuxiJiangsu 214023China department of dermatology Shandong Provincial Hospital for Skin Diseases&Shandong Provincial Institute of Dermatology and VenereologyShandong First Medical University&Shandong Academy of Medical SciencesJinanShandong 250022China department of dermatology Beijing Tsinghua Changgung HospitalBeijing 102218China department of dermatology Zhejiang Provincial People’s HospitalHangzhouZhejiang 310014China department of dermatology The First Affiliated Hospital of Xinxiang Medical CollegeXinxiangHenan 453100China department of dermatology Huashan Hospital Affiliated to Fudan UniversityShanghai 200040China department of dermatology General Hospital of Ningxia Medical UniversityYinchuanNingxia 750000China department of dermatology Affiliated Hospital of Chengde Medical UniversityChengdeHebei 067000China department of dermatology The First Hospital of Shanxi Medical UniversityTaiyuanShanxi 030001China department of dermatology Qilu Hospital of Shandong UniversityJinanShandong 250012China department of dermatology Yuebei People’s HospitalShaoguanGuangdong 512026China department of dermatology Union Hospital Tongji Medical Collage Huazhong University of Science and TechnologyWuhanHubei 430022China department of dermatology and Venereal Diseases The First Affiliated Hospit

Background:There is a need for effective and safe therapies for psoriasis that provide sustained *** aim of this study was to assess the efficacy and safety of tildrakizumab,an anti-interleukin-23p19 monoclonal antibody,for treating moderate-to-severe plaque psoriasis in Chinese ***:In this multi-center,double-blind,phase III trial,patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned(1:1)to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and *** initially assigned to placebo were switched to receive tildrakizumab at weeks 12,16,and every 12 weeks *** in the tildrakizumab group continued with tildrakizumab at week 16,and every 12 weeks until week *** primary endpoint was the Psoriasis Area and Severity Index(PASI 75)response rate at week ***:At week 12,tildrakizumab demonstrated significantly higher PASI 75 response rates(66.4%[73/110]vs.12.7%[14/110];difference,51.4%[95%confidence interval(CI),40.72,62.13];P<0.001)and Physician’s Global Assessment(60.9%[67/110]vs.10.0%[11/110];difference,49.1%[95%CI,38.64,59.62];P<0.001)compared to *** 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups,reaching maximal efficacy after 28 weeks(86.8%[92/106]vs.82.4%[89/108])and maintained up to 52 weeks(91.3%[95/104]vs.87.4%[90/103]).Most treatment-emergent adverse events were mild and not related to ***:Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque *** registration:***,NCT05108766.

关键词： Tildrakizumab Interleukin 23 Plaque psoriasis Chinese Randomized controlled trial

Clinical characteristics and outcomes of psoriasis patients with COVID-19: A retrospective, multicenter cohort study in China

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中华医学杂志(英文版) 2024年第14期137卷 1736-1743页

作者： Liu Yanhua Xu Zhongrui Zhou Jian Chen Aijun Zhang Junling Kang Xiaojing Jiang Xian Lyu Chengzhi Shi Chunrui Shi Yuling Liu Xiaoming Li Fuqiu Yang Bin Huang Yongmei Yu Chen Wang Gang department of dermatology Xijing Hospital Fourth Military Medical University Xi’an Shaanxi China department of dermatology The First Affiliated Hospital of Chongqing Medical University Chongqing China department of dermatology Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital Tianjin China department of dermatology and Venereology People’s Hospital of Xinjiang Uygur Autonomous Region Urumqi Xinjiang China department of dermatology West China Hospital Sichuan University Chengdu Sichuan China department of Psoriasis Dalian Dermatosis Hospital Dalian Liaoning China department of dermatology The First Hospital of Lanzhou University Lanzhou Gansu China Skin Disease hospital of Tongji University Shanghai China department of dermatology The University of Hong Kong-Shenzhen Hospital Shenzhen Guangdong China department of dermatology The Second Hospital of Jilin University Changchun Jilin China department of dermatology Dermatology Hospital of Southern Medical University Guangzhou Guangdong China department of dermatology Xining First People’s Hospital Xining Qinghai China

Background: Limited information exists regarding the impact of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection on psoriasis patients. The objective of this study was to identify clinical factors associated with the prognosis of psoriasis following SARS-CoV-2 ***: A retrospective, multicenter study was conducted between March and May 2023. Univariable and multivariable logistic regression analyses were employed to identify factors associated with coronavirus disease 2019 (COVID-19)-related psoriasis outcomes. The study included 2371 psoriasis patients from 12 clinical centers, with 2049 of them having been infected with ***: Among the infected groups, lower exacerbation rates were observed in individuals treated with biologics compared to those receiving traditional systemic or nonsystemic treatments (22.3% [236/1058]vs. 39.8% [92/231]vs. 37.5% [140/373],P <0.001). Psoriasis progression with lesions (adjusted odds ratio [OR] = 8.197, 95% confidence interval [95% CI] = 5.685–11.820, compared to no lesions), hypertension (adjusted OR = 1.582, 95% CI = 1.068–2.343), traditional systemic (adjusted OR = 1.887, 95% CI= 1.263–2.818), and nonsystemic treatment (adjusted OR= 1.602, 95% CI= 1.117–2.297) were found to be associated with exacerbation of psoriasis after SARS-CoV-2 infection, but not biologics (adjusted OR = 0.931, 95% CI = 0.680–1.274, compared to no treatment), according to multivariable logistic regression ***: A reduced risk of psoriasis exacerbation after SARS-CoV-2 infection was observed with biologics compared to traditional systemic and nonsystemic treatments. Significant risk factors for exacerbation after infection were identified as existing psoriatic lesions and hypertension.

关键词： COVID-19 SARS-CoV-2 Psoriasis Treatment Biologics

Efficacy and safety of CM310 in moderate-to-severe atopic dermatitis:A multicenter,randomized,double-blind,placebo-controlled phase 2b trial

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Chinese Medical Journal 2024年第2期137卷 200-208页

作者： Yan Zhao Jianzhong Zhang Bin Yang Jingyi Li Yangfeng Ding Liming Wu Litao Zhang Jinyan Wang Xiaohong Zhu Furen Zhang Xiaohua Tao Yumei Li Chunlei Zhang Linfeng Li Jianyun Lu Qingchun Diao Qianjin Lu Xiaoyong Man Fuqiu Li Xiujuan Xia Hao Cheng Yingmin Jia Guoqing Zhao Jinchun Yan Bo Chen department of dermatology Peking University People’s HospitalBeijing 100044China department of dermatology Dermatology HospitalSouthern Medical UniversityGuangzhouGuangdong 510091China department of dermatology West China HospitalSichuan UniversityChengduSichuan 610041China department of dermatology Shanghai Skin Disease HospitalInstitute of PsoriasisTongji University School of MedicineShanghai 200443China department of dermatology Affiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhouZhejiang 310006China department of dermatology Tianjin Academy of Traditional Chinese Medicine Affiliated HospitalTianjin 300120China department of dermatology Ningbo No.2 HospitalNingboZhejiang 315010China department of dermatology The Wuxi Second Affiliated Hospital of Nanjing Medical UniversityWuxiJiangsu 214002China Shandong Provincial hospital for Skin Diseases&Shandong Provincial Institute of dermatology and Veneorology Shandong First Medical University&Shandong Academy of Medical SciencesJinanShandong 250022China Center for Plastic&Reconstructive Surgery Department of DermatologyZhejiang Provincial People’s Hospital(Affiliated People’s HospitalHangzhou Medical College)HangzhouZhejiang 310014China department of dermatology Affiliated Hospital of Jiangsu UniversityZhenjiangJiangsu 212001China department of dermatology Peking University Third HospitalBeijing 100191China department of dermatology Beijing Friendship HospitalCapital Medical UniversityBeijing 100050China department of dermatology The Third Xiangya Hospital of Central South UniversityChangshaHunan 410013China department of dermatology Chongqing Traditional Chinese Medicine HospitalChongqing 400011China Hunan Key Laboratory of Medical Epigenomics Department of DermatologyThe Second Xiangya Hospital of Central South UniversityChangshaHunan 410011China department of dermatology The Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Departme

Background:Atopic dermatitis(AD)affects approximately 10%of adults ***310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 *** trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe ***:This multicenter,randomized,double-blind,placebo-controlled,phase 2b trial was conducted in 21 medical institutions in China from February to November *** 120 eligible patients were enrolled and randomized(1:1:1)to receive subcutaneous injections of 300 mg CM310,150 mg CM310,or placebo every 2 weeks for 16 weeks,followed by an 8-week follow-up *** primary endpoint was the proportion of patients achieving≥75%improvement in the Eczema Area and Severity Index(EASI-75)score from baseline at week *** and pharmacodynamics were also ***:At week 16,the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups(70%[28/40]for high-dose and 65%[26/40]for low-dose)than that in the placebo group(20%[8/40]).The differences in EASI-75 response rate were 50%(high ***,95%CI 31%-69%)and 45%(low ***,95%CI 26%-64%),with both P valuesdermatology Life Quality Index compared with ***310 treatment reduced levels of thymus and activation-regulated chemokine,total immunoglobulin E,lactate dehydrogenase,and blood *** incidence of treatment-emergent adverse events(TEAEs)was similar among all three groups,with the most common TEAEs reported being upper respiratory tract infection,atopic dermatitis,hyperlipidemia,and *** severe adverse events were deemed to be attributed to ***:CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tol

关键词： CM310 Moderate-to-severe atopic dermatitis Interleukin-4 receptor alpha Adults