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Dapagliflozin in heart failure and type 2 diabetes:Efficacy,cardiac and renal effects,safety

World Journal of Diabetes 2024年第7期15卷 1518-1530页

作者： Pei-Ling Yu You Yu Shuang Li Bai-Chen Mu Ming-Hua Nan Min Pang The Second department of Cardiology The Second Affiliated Hospital of Liaoning Hospital of Traditional Chinese MedicineShenyang 110034Liaoning ProvinceChina department of outpatient The Second Affiliated Hospital of Liaoning University of Traditional Chinese MedicineShenyang 110034Liaoning ProvinceChina

BACKGROUND Heart failure(HF),especially HF with reduced ejection fraction(HFrEF),presents complex challenges,particularly in the aging population where it often coexists with type 2 diabetes mellitus(T2DM).AIM To analyze the effect of dapagliflozin treatment on cardiac,renal function,and safety in patients with HFrEF combined with *** Patients with T2DM complicated with HFrEF who underwent treatment in our hospital from February 2018 to March 2023 were retrospectively analyzed as the subjects of this *** propensity score matching method was used,and a total of 102 eligible samples were *** clinical efficacy of the two groups was evaluated at the end of the treatment,comparing the results of blood glucose,insulin,cardiac function,markers of myocardial injury,renal function indexes,and 6-min walk test(6MWT)before and after the *** compared the occurrence of adverse effects on the treatment process of the two groups of *** incidence of adverse outcomes in patients within six months of treatment was *** The overall clinical efficacy rate of patients in the study group was significantly higher than that of patients in the control group(P=0.013).After treatment,the pancreatic beta-cell function index,left ventricular ejection fraction,and glomerular filtration rate of patients in the study group were significantly higher than control group(P<0.001),while their fasting plasma glucose,2-h postprandial glucose,glycosylated hemoglobin,insulin resistance index,left ventricular end-systolic diameter,left ventricular end-diastolic diameter,cardiac troponin I,creatine kinase-MB,N-terminal pro b-type natriuretic peptide,serum creatinine,and blood urea nitrogen were significantly lower than those of the control *** treatment,patients in the study group had a significantly higher 6MWT than those in the control group(P<0.001).Hypoglycemic reaction(P=0.647),urinary tract infection(P=0.558),gastrointestinal adverse effect(P=0.

关键词： Heart failure Type 2 diabetes mellitus Heart failure with preserved ejection fraction Myocardial infarction markers Cardiac function

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Diagnosis and treatment experience of atypical hepatic cystic echinococcosis type 1 at a tertiary center in China

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World Journal of Gastroenterology 2024年第5期30卷 462-470页

作者： Yu-Peng Li Jie Zhang Zhi-De Li Chao Ma Guang-Lei Tian Yuan Meng Xiong Chen Zhi-Gang Ma department of Hepatobiliary Surgery People's Hospital of Xinjiang Uygur Autonomous RegionUrumqi 830000Xinjiang Uygur Autonomous RegionChina

BACKGROUND Some hydatid cysts of cystic echinococcosis type 1(CE1)lack well-defined cyst walls or distinctive endocysts,making them difficult to differentiate from simple hepatic *** To investigate the diagnostic methods for atypical hepatic CE1 and the clinical efficacy of laparoscopic *** The clinical data of 93 patients who had a history of visiting endemic areas of CE and were diagnosed with cystic liver lesions for the first time at the People's Hospital of Xinjiang Uygur Autonomous region(China)from January 2018 to September 2023 were retrospectively *** diagnoses were made based on findings from serum immunoglobulin tests for echinococcosis,routine abdominal ultrasound,high-frequency ultrasound,abdominal computed tomography(CT)scan,and *** to the treatments,these patients underwent reexaminations at the outpatient clinic until October *** evaluations included the diagnostic precision of diverse examinations,the efficacy of surgical approaches,and the incidence of CE *** All 93 patients were diagnosed with simple hepatic cysts by conventional abdominal ultrasound and abdominal CT *** them,16 patients were preoperatively diagnosed with atypical CE1,and 77 were diagnosed with simple hepatic cysts by high-frequency *** the 16 patients preoperatively diagnosed with atypical CE1 underwent laparoscopy,of whom 14 patients were intraoperatively confirmed to have CE1,which was consistent with the postoperative pathological diagnosis,one patient was diagnosed with a mesothelial cyst of the liver,and the other was diagnosed with a hepatic cyst combined with local *** the 77 patients who were preoperatively diagnosed with simple hepatic cysts,4 received aspiration sclerotherapy of hepatic cysts,and 19 received laparoscopic *** patients were intraoperatively diagnosed with simple hepatic *** the followup period,none of the 14 patients with CE1 expe

关键词： Hepatic echinococcosis Hepatic cystic echinococcosis type 1 Hepatic cyst Color Doppler ultrasound Laparoscopy

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Success of susceptibility-guided eradication of Helicobacter pylori in a region with high secondary clarithromycin and levofloxacin resistance rates

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World Journal of Gastroenterology 2024年第2期30卷 184-195页

作者： Yan-Meng Wang Mo-Ye Chen Jing Chen Xin-He Zhang Yan Feng Yu-Xi Han Yi-Ling Li department of Gastroenterology The First Affiliated Hospital of China Medical UniversityShenyang 110000Liaoning ProvinceChina Key Laboratory of Cancer Etiology and Prevention in liaoning Education department The First Hospital of China Medical UniversityShenyang 110000Liaoning ProvinceChina

BACKGROUND Resistance to clarithromycin(CLA)and levofloxacin(LFX)of Helicobacter pylori(***)is increasing in severity,and successful eradication is ***,the eradication success rate has greatly declined,leaving a large number of patients with previous treatment *** To investigate secondary resistance rates,explore risk factors for antibiotic resistance,and assess the efficacy of susceptibility-guided *** We recruited 154 subjects positive for Urea Breath Test who attended The First Affiliated Hospital of China Medical University between July 2022 and April *** underwent a string test after an overnight *** gastric juice was obtained and transferred to vials containing storage ***,DNA extraction and the specific DNA amplification were performed using quantitative polymerase chain reaction(qPCR).Demographic information was also analyzed as part of the *** on these results,the participants were administered susceptibility-guided *** was compared with that of the empiric treatment *** A total of 132 individuals tested positive for the *** ureA gene by qPCR *** resistance rate reached a high level of 82.6%(n=109),LFX resistance rate was 69.7%(n=92)and dual resistance was 62.1%(n=82).Gastric symptoms[odds ratio(OR)=2.782;95%confidence interval(95%CI):1.076-7.194;P=0.035]and rural residence(OR=5.152;95%CI:1.407-18.861;P=0.013)were independent risk factors for secondary resistance to CLA and LFX,respectively.A total of 102 and 100 individuals received susceptibility-guided therapies and empiric treatment,*** antibiotic susceptibility-guided treatment and empiric treatment groups achieved successful eradication rates of 75.5%(77/102)and 59.0%(59/411)by the intention-to-treat(ITT)analysis and 90.6%(77/85)and 70.2%(59/84)by the per-protocol(PP)analysis,*** eradication rates of these two treatment strategies were significantly

关键词： Helicobacter pylori Antibiotic resistance Clarithromycin Levofloxacin String-test Susceptibility-guided therapy Eradication rate

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Nicotine up-regulates SLC7A5 expression depending on TRIM29 in non-small cell lung cancer

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Genes & Diseases 2024年第2期11卷 582-584页

作者： Dahua Liu Haolin Ren Guimin Wen Pu Xia Biological Anthropology Institute College of Basic Medical ScienceJinzhou Medical UniversityJinzhouLiaoning 121000China department of Radiology The First Affiliated Hospital of Dalian Medical UniversityDalianLiaoning 116011China department of Community Nursing College of NursingJinzhou Medical UniversityJinzhouLiaoning 121000China

Non-small cell lung cancer(NSCLC)is a malignant tumor that poses a serious threat to human ***(LUAD)and squamous cell carcinoma(LUSC)are two common types of *** originate from glandular and squamous cells of the bronchial epithelium,*** gene changes during tumorigenesis is conducive to the selection of suitable treatment methods for ***98 is a heterodimeric transmembrane glycoprotein,which is composed of a heavy chain and a light chain.1 cD98 heavy chain(CD98hc),also known as 4F2hc or SLC3A2,is an 85kDa type ll transmembraneglycoprotein,which consists of a cytoplasmic region(NH2 terminal),a single chain transmembrane region,and a huge extracellular region(COOH terminal).1 CD98hc can combine with the CD98 light chain,LAT1(SLC7A5),to form CD98 protein through disulfide bonds.1 SLC7A5 is a 12 times transmembrane helix bundle protein composed of 501-535 amino acid residues1.

关键词： lung cancer NSCLC

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Zinc finger protein 831 promotes apoptosis and enhances chemosensitivity in breast cancer by acting as a novel transcriptional repressor targeting the STAT3/Bcl2 signaling pathway

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Genes & Diseases 2024年第1期11卷 430-448页

作者： Jun Fan Zhe Zhang Hongqiang Chen Dongjiao Chen Wenbo Yuan Jingzhi Li Yong Zeng Shimeng Zhou Shu Zhang Gang Zhang Jiashen Xiong Lu Zhou Jing Xu Wenbin Liu Yan Xu department of Breast and Thyroid Surgery Daping HospitalArmy Medical University(Third Military Medical University)Chongqing 400042China Institute of Toxicology College of Preventive MedicineArmy Medical University(Third Military Medical University)Chongqing 400038China department of Environmental Health College of Preventive MedicineArmy Medical University(Third Military Medical University)Chongqing 400038China Anesthesia and Intensive Care Chinese University of Hong KongHong Kong SAR 999077China School of Public Health Xinxiang Medical UniversityXinxiangHenan 453003China School of Public Health China Medical UniversityShenyangLiaoning 110122China

Emerging evidence suggested that zinc finger protein 831(ZNF831)was associated with immune activity and stem cell regulation in breast ***,the roles and molec-ular mechanisms of ZNF831 in oncogenesis remain ***831 expression was significantly diminished in breast cancer which was associated with promoter CpG methylation but not *** over-expression of ZNF831 suppressed breast cancer cell proliferation and col-ony formation and promoted apoptosis in vitro,while knockdown of ZNF831 resulted in an opposite ***-proliferation effect of ZNF831 was verified in *** analysis of public databases and transcriptome sequencing both showed that ZNF831 could enhance apoptosis through transcriptional regulation of the JAK/STAT *** and luciferase report assays demonstrated that ZNF831 could directly bind to one specific region of STAT3 promoter and induce the transcriptional inhibition of *** a result,the attenuation of STAT3 led to a restraint of the transcription of Bcl2 and thus accelerated the apoptotic *** of STAT3 diminished the apoptosis-promoting effect of ZNF831 in breast cancer cell ***,ZNF831 could ameliorate the anti-proliferation effect of capecitabine and gemcitabine in breast cancer cell *** findings demonstrate for the first time that ZNF831 is a novel transcriptional suppressor through inhibiting the expression of STAT3/Bcl2 and promoting the apoptosis process in breast cancer,suggesting ZNF831 as a novel biomarker and potential therapeutic target for breast cancer patients.

关键词： Apoptosis Breast cancer Chemosensitivity STAT3 ZNF831

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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

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Association of a complete breast cancer pathologic response with axillary lymph node metastasis via neoadjuvant chemotherapy:Results from the CSBrS-012 study

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Chinese Medical Journal 2024年第11期137卷 1369-1371页

作者： Le Ma Pin Gao Zhenzhen Liu Dechuang Jiao Rui Ling Jingjing Xiao Yi Zhao Yitong Wang Hongjian Yang Yunjiang Liu Ke Liu Jianguo Zhang Guangyan Li Dahua Mao Yinglei Deng Jianjun He Maimaitiaili Amina Zhigang Yu Wang Fei Yinhua Liu Peifen Fu Minya Yao Jiandong Wang Li Zhu Hongchuan Jiang Zuowei Zhao Xingsong Tian Zhongwei Cao Xinyu Ma Kejin Wu Shaomei Fu Ailin Song Yanwei Wang Jin Feng Zhimin Fan department of Breast Surgery General Surgery CenterThe First Hospital of Jilin UniversityChangchunJilin 130021China department of Breast Disease Henan Breast Cancer CenterAffiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalZhengzhouHenan 450008China department of Thyroid Breast and Vascular SurgeryXijing HospitalFourth Military Medical UniversityXi’anShaanxi 710032China Surgical Oncology department Shengjing Hospital of China Medical UniversityShenyangLiaoning 110022China department of Breast Surgery The Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital)Institute of Basic Medicine and Cancer(IBMC)Chinese Academy of SciencesHangzhouZhejiang 310022China department of Surgery The Fourth Hospital of Hebei Medical UniversityShijiazhuangHebei 052360China Fourth department of Breast Surgery Jilin Cancer HospitalChangchunJilin 130012China department of Breast Surgery The Second Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjiang 150086China department of Breast Surgery Affiliated Wudang Hospital of Guizhou Medical UniversityGuiyangGuizhou 550009China department of Breast Surgery The First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anShaanxi 710061China department of Breast Surgery The Second HospitalCheeloo College of MedicineShandong UniversityJinanShandong 250033China Breast Disease Center Peking University First HospitalBeijing 100034China department of Breast Surgery The First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouZhejiang 310003China department of General Surgery The First Medical CenterChinese PLA General HospitalBeijing 100852China department of Breast Surgery Beijing Chaoyang HospitalCapital Medical UniversityBeijing 100020China department of Breast Surgery The Second Affiliated Hospital of Dalian Medical UniversityDalianLiaoning 116023China department of Breast and Thyroid Surgery Shandong Provincial Hospital Affiliated to Shandong UniversityJinan

To the Editor:In the last decade,neoadjuvant chemotherapy(NAC)has become a well-accepted treatment option for breast cancer,although few detailed description of NAC in China has yet been reported.[1]A previous study found that among patients with clinically node-negative(cN0)breast cancer,97.7%(432/442)with breast pathologic complete response(bpCR)had ypN0(absence of metastases in the axillary lymph nodes);and 71.6%(882/1232)without bpCR achieved ypN0(P<0.001).As for human epidermal growth factor receptor 2(HER2)positive or triple-negative breast cancer(TNBC)that achieved bpCR.

关键词： breast pathologic chemotherapy

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Circulating glycated albumin levels and gestational diabetes mellitus

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World Journal of Diabetes 2024年第8期15卷 1802-1810页

作者： Wei Xiong Zhao-Hui Zeng Yuan Xu Hui Li Hui Lin department of Medical Hunan Traditional Chinese Medical CollegeZhuzhou 412012Hunan ProvinceChina department of outpatient Zhuzhou Second HospitalZhuzhou 412012Hunan ProvinceChina

BACKGROUND Gestational diabetes mellitus(GDM)is characterized by glucose intolerance that is first diagnosed during pregnancy,making it the most common complication associated with this *** detection and targeted treatment of GDM can minimize foetal exposure to maternal hyperglycaemia and subsequently reduce the associated adverse pregnancy *** studies have inconsistently suggested that the level of glycated albumin(GA)might predict *** To review and synthesize existing evidence to evaluate the relationship between GA levels and the development of *** We sought to compare GA levels between GDM and control groups in this metaanalysis by systematically searching the Web of Science,PubMed,Cochrane Library,and Embase databases for articles published up to June *** analysis utilized the weighted mean difference(WMD)as the primary *** data were meticulously extracted,and the quality of the included studies was ***,we conducted a subgroup analysis based on study region and sample *** assessed heterogeneity using I2 statistics and evaluated publication bias through funnel ***,trim-and-fill analysis was employed to detect and address any potential publication *** The meta-analysis included a total of 11 studies involving 5477 participants,comprising 1900 patients with GDM and 3577 control *** synthesized results revealed a notable correlation between elevated GA levels and increased susceptibility to *** calculated WMD was 0.42,with a 95%confidence interval(95%CI)ranging from 0.11 to 0.74,yielding a P value less than *** specific GA levels,the mean GA level in the GDM group was 12.6,while for the control group,it was lower,at *** discrepancy underscores the potential of GA as a biomarker for assessing GDM ***,we explored the levels of glycated haemoglobin(HbA1c)in both *** WMD for HbA1c was 0.19,with a 95%CI ranging from 0.15 to 0.

关键词： Glycated albumin Gestational diabetes mellitus Diabetes mellitus Meta-analysis Weighted mean difference

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Development of functional dye with redshifted absorption based on Knoevenagel condensation at 1-site in phenyl[b]-fused BODIPY

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Chinese Chemical Letters 2024年第6期35卷 349-352页

作者： Tianze Wang Junyi Ren Dongxiang Zhang Huan Wang Jianjun Du Xin-Dong Jiang Guiling Wang liaoning&Shenyang Key Laboratory of Functional Dye and Pigment Shenyang University of Chemical TechnologyShenyang 110142China department of Cell Biology China Medical UniversityShenyang 110122China State Key Laboratory of Fine Chemicals Dalian University of TechnologyDalian 116024China

Integrating ring-fused modification withπ-conjugated extension is an effective approach for designing,synthesizing,and application for novel borondipyrromethene(BODIPY)*** this work,based on phenyl[b]-fused BODIPY,we made reasonable modification of the methyl group at 1-site to generate dye *** possessed near-infrared region(NIR)absorption and emission properties,and the intramolecular charge transfer(ICT)resulted in low ***,heat energy is evidently released in the presence of light,which can be exploited for intracellular photothermal therapy via the cell apoptosis process,reducing the inflammatory side-effects induced by *** research provides a crucial foundation for the novel molecule via BODIPY multi-directional alteration and its potential application in anti-tumor phototherapy.

关键词： NIR dyes [b]-Fused BODIPY Knoevenagel condensation Photothermal therapy Cell apoptosis

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Expert Consensus on the Treat-to-Target Strategy for Psoriasis With Biological Agents in China(Simplified Edition)

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International Journal of Dermatology and Venereology 2024年第2期7卷 61-69页

作者： Ai-Jun Chen Da-Xing Cai Xiang Chen Yong Cui Yan Ding Heng Gu Xing-Hua Gao Chao Ji Xiao-Jing Kang Ye-Hong Kuang Cheng-Zhi Lyu Min Li Wei Li Xia Li Yu-Zhen Li Xiao-Yong Man Jian-Jun Qiao Juan Su Liang-Dan Sun Yu-Ling Shi Juan Tao Jian-Xin Xia Rong Xiao Bin Yang Wu Zhu Xue-Jun Zhang Committee on Psoriasis Dermatology and Venereology Branch of the Chinese Medical Association department of Dermatology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China department of Dermatology Qilu HospitalShandong UniversityJinanShandong 250100China department of Dermatology Xiangya HospitalCentral South UniversityChangshaHunan 410008China department of Dermatology China-Japan Friendship HospitalBeijing 100192China department of Dermatology Hainan Provincial Hospital of Skin DiseaseHaikouHainan 570311China department of Dermatology Hospital for Skin DiseasesChinese Academy of Medical SciencesNanjingJiangsu 210042China department of Dermatology The First Hospital of China Medical UniversityShenyangLiaoning 110002China department of Dermatology The First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian 350004China department of Dermatology People’s Hospital of Xinjiang Uygur Autonomous RegionUrumqiXinjiang Uyghur Autonomous Region 830001China department of Dermatology Dalian Dermatosis HospitalDalianLiaoning 116021China department of Dermatology Dushu Lake Hospital Affiliated to Soochow UniversitySuzhouJiangsu 215127China department of Dermatology West China Hospital of Sichuan UniversityChengduSichuan 610044China department of Dermatology Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China department of Dermatology The Second Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjiang 150086China department of Dermatology The Second Affiliated Hospital of Zhejiang University School of MedicineHangzhouZhejiang 310003China department of Dermatology The First Affiliated Hospital of Zhejiang University School of MedicineHangzhouZhejiang 310003China department of Dermatology The First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui 230022China department of Dermatology Shanghai Skin Disease HospitalTongji University School of MedicineShanghai 200093China department of Dermatology The Union Hospital of Tongji Medical CollegeHuazhong University of Science and Te

Psoriasis is a chronic,recurrent,inflammatory systemic disease that is not only characterized by skin manifestations but may also be accompanied by various comorbidities,imposing a heavy burden on patients’physical and mental health and affecting their quality of *** the continuous approval of various biological agents for clinical use has provided more effective treatment options to patients with psoriasis,no consensus on the evaluation of comprehensive treatment goals has yet been *** treat-to-target(T2T)strategy requires consideration of multiple dimensions of treatment outcomes,the development of long-term management goals,and regular assessments of treatment conditions,which are often used in the management of chronic ***,based on the latest consensuses and guidelines,research data,and clinical experience as well as the combination of survey results and expert group discussions,the present consensus focuses on 4 dimensions of short-and long-term integrated management goals for biological agents:alleviating skin lesions,improving quality of life,screening and managing psoriasis comorbidities,and ensuring drug *** implementation methods,evaluation time,treatment monitoring,and program adjustments are also herein described to achieve comprehensive management of psoriasis to the maximum *** consensus provides a reference for clinical practice.

关键词： psoriasis biological agents treat-to-target comorbidity consensus

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