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Digital pathology-based artificial intelligence models for differential diagnosis and prognosis of sporadic odontogenic keratocysts

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International Journal of Oral Science 2024年第2期16卷 349-358页

作者： Xinjia Cai Heyu Zhang Yanjin Wang Jianyun Zhang Tiejun Li Department of Oral Pathology Peking University School and Hospital of Stomatology&National Center of Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijingChina Central Laboratory Peking University School and Hospital of StomatologyBeijingChina Department of Oral Pathology Shanghai Stomatological Hospital&School of StomatologyFudan UniversityShanghaiChina Research Unit of Precision Pathologic Diagnosis in Tumors of the Oral and Maxillofacial Regions Chinese Academy of Medical Sciences(2019RU034)BeijingChina

Odontogenic keratocyst(OKC)is a common jaw cyst with a high recurrence *** combined with basal cell carcinoma as well as skeletal and other developmental abnormalities is thought to be associated with Gorlin ***,OKC needs to be differentiated from orthokeratinized odontogenic cyst and other jaw *** of the different prognosis,differential diagnosis of several cysts can contribute to clinical *** collected 519 cases,comprising a total of 2157 hematoxylin and eosinstained images,to develop digital pathology-based artificial intelligence(AI)models for the diagnosis and prognosis of *** Inception_v3 neural network was utilized to train and test models developed from patch-level ***,whole slide imagelevel AI models were developed by integrating deep learning-generated pathology features with several machine learning *** AI models showed great performance in the diagnosis(AUC=0.935,95%CI:0.898–0.973)and prognosis(AUC=0.840,95%CI:0.751–0.930)of *** advantages of multiple slides model for integrating of histopathological information are demonstrated through a comparison with the single slide ***,the study investigates the correlation between AI features generated by deep learning and pathological findings,highlighting the interpretative potential of AI models in the ***,we have developed the robust diagnostic and prognostic models for *** AI model that is based on digital pathology shows promise potential for applications in odontogenic diseases of the jaw.

关键词： diagnosis pathology prognosis

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Genomic alterations in oral multiple primary cancers

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International Journal of Oral Science 2024年第1期16卷 145-153页

作者： Wen Wang Qian Wang Shiying Sun Pengfei Zhang Yuyu Li Weimin Lin Qiwen Li Xiao Zhang Zhe Ma Haiyan Lu Hebei key Laboratory of Stomatology Hebei Clinical Research Center for Oral DiseasesHebei Medical UniversityShijiazhuangChina Department of Orthodontics School and Hospital of StomatologyHebei Medical UniversityShijiazhuangChina State key Laboratory of Oral Diseases&national Center for Stomatology&national clinical Research Center for Oral Diseases&West China Hospital of Stomatology Sichuan UniversityChengduChina Department of Preventive Dentistry School and Hospital of StomatologyHebei Medical UniversityShijiazhuangHebeiChina

Oral squamous cell carcinoma (OSCC) is the predominant type of oral cancer, while some patients may develop oral multiple primary cancers (MPCs) with unclear etiology. This study aimed to investigate the clinicopathological characteristics and genomic alterations of oral MPCs. Clinicopathological data from patients with oral single primary carcinoma (SPC, n=202) and oral MPCs (n=34) were collected and compared. Copy number alteration (CNA) analysis was conducted to identify chromosomal-instability differences among oral MPCs, recurrent OSCC cases, and OSCC patients with lymph node metastasis. Whole-exome sequencing was employed to identify potential unique gene mutations in oral MPCs patients. Additionally, CNA and phylogenetic tree analyses were used to gain preliminary insights into the molecular characteristics of different primary tumors within individual patients. Our findings revealed that, in contrast to oral SPC, females predominated the oral MPCs (70.59%), while smoking and alcohol use were not frequent in ***, long-term survival outcomes were poorer in oral MPCs. From a CNA perspective, no significant differences were observed between oral MPCs patients and those with recurrence and lymph node metastasis. In addition to commonly mutated genes such as CASP8, TP53 and MUC16, in oral MPCs we also detected relatively rare mutations, such as HS3ST6 and RFPL4A. Furthermore, this study also demonstrated that most MPCs patients exhibited similarities in certain genomic regions within individuals, and distinct differences of the similarity degree were observed between synchronous and metachronous oral MPCs.

关键词： alterations metastasis oral

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Natural long-chain saturated fatty acids doped LNPs enabling spleen selective mRNA translation and potent cancer immunotherapy

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Nano Research 2024年第3期17卷 1804-1817页

作者： Fazhan Wang Meng Zhang Meiling Tian Jia Lou Longze Pan Xiaoke Gao Lijing Zhang Xiaohan Lou Linyu Zhu Yuqiao Sheng Ming Wang Rui Xue Wenjing Deng Shuai Shao Zhihai Qin Medical Research Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450052China Translational Medical Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450052China Department of Neuro-Intensive Care Unit The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Academy of Medical Sciences Zhengzhou UniversityZhengzhou 450052China

Rationally tailored lipid nanoparticles(LNPs)with efficient and tunable delivery of mRNA in vivo are crucial for mRNA *** expression of antigenic protein in lymphoid tissues/organs could improve the immunostimulatory efficacy and safety of LNPs-based mRNA *** by the metabolic behavior that long-chain saturated fatty acids tending to enter lymphoid tissue rather than the liver,we developed fatty acid-doped LNPs capable of mediating differential protein expressions in the liver and spleen when administered *** the molar ratio of saturated fatty acid located 60%–70%,the doped LNPs achieved the spleen selective mRNA *** mechanism could be attributed to the different cellular uptake behaviors of saturated fatty acids in *** with a model antigen(ovalbumin)mRNA-loaded spleen selective LNPs,we observed enhanced antigen-specific T cell immune responses,and potent immunotherapeutic and immunoprophylactic efficacy in the mouse lymphoma *** natural long-chain saturated fatty acids metabolic characteristics-inspired design of LNPs for spleen-selective mRNA vaccines delivery will provide references for designing mRNA vaccines with high efficacy and safety for tumor immunotherapy.

关键词： mRNA vaccine lipid nanoparticles spleen long-chain saturated fatty acid cancer immunotherapy

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Anti-N-methyl-D-aspartate receptor type autoimmune encephalitis with severe pneumonia:a case report

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World Journal of Emergency Medicine 2024年第2期15卷 142-146页

作者： Yi Gu Xiandong Liu Tiancao Dong Qian Yang Xiaowei Bao Dongyang Zhao Lunxian Tang Department of Internal Emergency Medicine Shanghai East HospitalSchool of MedicineTongji UniversityShanghai 200120China School of Medicine Tongji UniversityShanghai 200120China

Autoimmune encephalitis(AE)is a type of encephalitis caused by autoimmune *** was included on a list of the first batch of 121 rare diseases published by the Chinese national Health Commission on 11^(th)May ***,patients with AE account for 10%-20% of encephalitis cases,with 54%-80% of those cases classified as the anti-N-methyl-D-aspartate receptor(NMDAR)type,which is the most common type.[1]In 2010,China reported the first case of a patient withanti-NMDARtype AE.

关键词： encephalitis autoimmune aspartate

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Disruption of PABPN1 phase separation by SNRPD2 drives colorectal cancer cell proliferation and migration through promoting alternative polyadenylation of CTNNBIP1

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Science China(Life Sciences) 2024年第6期67卷 1212-1225页

作者： Zhijie Hu Mengxia Li Yufeng Chen Liutao Chen Yuting Han Chengyong Chen Xin Lu Nan You Yawen Lou Yingye Huang Zhanfeng Huo Chao Liu Cheng Liang Susu Liu Ke Deng Liangfu Chen Shangwu Chen Guohui Wan Xiaojian Wu Yonggui Fu Anlong Xu State key Laboratory of Biocontrol Guangdong Province Key Laboratory of Pharmaceutical Functional GenesDepartment of BiochemistrySchool of Life SciencesSun Yat-sen UniversityGuangzhou 510275China Department of General Surgery(Colorectal Surgery)&Guangdong Provincial key Laboratory of Colorectal and Pelvic Floor Diseases&Biomedical Innovation Center The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510655China national-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation National Engineering Research Center for New Drug and Druggability(cultivation)Guangdong Province Key Laboratory of New Drug Design and EvaluationSchool of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhou 510006China School of Life Sciences Beijing University of Chinese MedicineBeijing 100029China

Generally shortened 3′UTR due to alternative polyadenylation(APA)is widely observed in cancer,but its regulation mechanisms for cancer are not well ***,with profiling of APA in colorectal cancer tissues and poly(A)signal editing,we firstly identified that the shortened 3′UTR of CTNNIBP1 in colorectal cancer promotes cell proliferation and *** found that liquid-liquid phase separation(LLPS)of PABPN1 is reduced albeit with higher expression in cancer,and the reduction of LLPS leads to the shortened 3′UTR of CTNNBIP1and promotes cell proliferation and ***,the splicing factor SNRPD2 upregulated in colorectal cancer,can interact with glutamic-proline(EP)domain of PABPN1,and then disrupt LLPS of PABPN1,which attenuates the repression effect of PABPN1 on the proximal poly(A)*** results firstly reveal a new regulation mechanism of APA by disruption of LLPS of PABPN1,suggesting that regulation of APA by interfering LLPS of 3′end processing factor may have the potential as a new way for the treatment of cancer.

关键词： alternative polyadenylation colorectal cancer CTNNBIP1 PABPN1 liquid-liquid phase separation SNRPD2

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RIPK1 plays a crucial role in maintaining regulatory T-Cell homeostasis by inhibiting both RIPK3-and FADD-mediated cell death

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Cellular & Molecular Immunology 2024年第1期21卷 80-90页

作者： Xiaoxue Deng Lingxia Wang Yunze Zhai Qiuyue Liu Fengxue Du Yu Zhang Wenxing Zhao Tingtao Wu Yiwen Tao Jie Deng Yongbing Cao Pei Hao Jiazi Ren Yunli Shen Zuoren Yu Yuejuan Zheng Haibing Zhang Haikun Wang State key Laboratory of Cardiology Shanghai East HospitalTongji University School of MedicineShanghai200120China CAS key Laboratory of Molecular Virology and Immunology Shanghai Institute of Immunity and InfectionChinese Academy of SciencesUniversity of Chinese Academy of SciencesShanghai200031China CAS key Laboratory of Nutrition Metabolism and Food SafetyShanghai Institute of Nutrition and HealthShanghai Institutes for Biological SciencesUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai200031China The Research Center for Traditional Chinese Medicine Shanghai Institute of Infectious Diseases and BiosecurityShanghai University of Traditional Chinese MedicineShanghai201203China Institute of Vascular Disease Shanghai TCM-Integrated HospitalShanghai University of Traditional Chinese MedicineShanghai200433China

Regulatory T(T_(reg))cells play an essential role in maintaining immune balance across various physiological and pathological ***,the mechanisms underlying T_(reg)homeostasis remain incompletely ***,we report that RIPK1 is crucial for T_(reg) cell survival and *** generated mice with T_(reg) cell-specific ablation of Ripk1 and found that these mice developed fatal systemic autoimmunity due to a dramatic reduction in the Treg cell compartment caused by excessive cell *** conventional T cells,Treg cells with Ripk1 deficiency were only partially rescued from cell death by blocking FADD-dependent ***,simultaneous removal of both Fadd and Ripk3 completely restored the homeostasis of Ripk1-deficient Treg cells by blocking two cell death ***,our study highlights the critical role of RIPK1 in regulating Treg cell homeostasis by controlling both apoptosis and necroptosis,thereby providing novel insights into the mechanisms of Treg cell homeostasis.

关键词： Treg cell Homeostasis Apoptosis Necroptosis

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Thyroid Hormone Biomonitoring:A Review on Their Metabolism and Machine-Learning Based Analysis on Effects of Endocrine Disrupting Chemicals

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Environment & Health 2024年第6期2卷 350-372页

作者： Shijie Chen Mengjie Yu Yiming Yao Yongcheng Li Ana He Zijun Zhou Liyang Pan Nan Xiao Haining Luo Hongwen Sun MOE key Laboratory of Pollution Processes and Environmental Criteria College of Environmental Science and EngineeringNankai UniversityTianjin 300071China Tianjin Tianshi College Tianjin 301700China Dalian Center for Disease Control and Prevention DalianLiaoning Province 116000China Department of Center for Reproductive Medicine Tianjin Central Hospital Of Gynecology Obstetrics/Tianjin Key Laboratory Of Human Development And Reproductive RegulationTianjin 300052China

The thyroid is an essential endocrine organ in human body,and thyroid hormones(THs)are pivotal signaling molecules and mediators in various physiological ***,particularly in their free form,play a critical role in regulating body temperature and in the metabolism of lipid and glucose,making the maintenance of TH levels crucial for human *** undergo a series of metabolic processes,producing TH metabolites(THMs).THMs are significant in endocrine regulation,such as 3,5-diiothyronine(3,5-T2)and 3-iodothyronamine(3-T1AM),which exhibit activities akin to *** production and distribution of THMs are intricately linked to the function of specific organs and tissues,highlighting the need for advanced research into the determination and mechanisms of THMs in *** to endocrine disrupting chemicals(EDCs)can significantly affect the levels of thyroid stimulating hormone(TSH)and *** review utilizes machine learning to analyze epidemiological data,identifying potential EDCs that pose risks of hyperthyroidism and ***,it delves into the toxicological mechanisms of these EDCs,examining their effects on TH production,binding processes,related proteins,and metabolic *** approach effectively bridges the gap between epidemiological studies and toxicological researches,laying the groundwork for future research *** integrating epidemiological studies with machine learning,this review offers insightful perspectives on the potential risks associated with chemical exposure and underscores the necessity for further research in understanding the impact of EDCs on TH metabolism and TH-related health effects.

关键词： Thyroid stimulating hormone Emerging contaminants Data mining Thyroxine 3,3′,5-Triiodothyronine Homeostasis

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Association of Cytokines with clinical Indicators in Patients with Drug-Induced Liver Injury

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Biomedical and Environmental Sciences 2024年第5期37卷 494-502页

作者： CAO Wei Hua JIANG Ting Ting SHEN Ge DENG Wen WANG Shi Yu ZHANG Zi Yu LI Xin Xin LU Yao ZHANG Lu LIU Ru Yu CHANG Min WU Shu Ling GAO Yuan Jiao HAO Hong Xiao CHEN Xiao Xue HU Lei Ping XU Meng Jiao YI Wei XIE Yao LI Ming Hui Department of Hepatology Division 2 Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China Department of Hepatology Division 2 Peking University Ditan Teaching HospitalBeijing 100015China Department of Gynecology and Obstetrics Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical *** The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with *** on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),antiinfective drugs,and other drugs,patients were divided into five *** were measured by Luminex *** characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were *** 73 patients were *** among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine ***-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs *** was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs *** Older age may be more prone to *** with NSAIDs have more severe liver damage in early stages of DILI,TNF-αand IL-6 may partake the inflammatory process of DILI.

关键词： Drug-induced liver injury Cytokines Non-steroidal anti-inflammatory drugs Inflammation

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Real-world effectiveness of early insulin therapy on the incidence of cardiovascular events in newly diagnosed type 2 diabetes

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2953-2959页

作者： Sihui Luo Xueying Zheng Wei Bao Sheng Nie Yu Ding Tong Yue Yilun Zhou Ying Hu Hua Li Qiongqiong Yang Qijun Wan Bicheng Liu Hong Xu Guisen Li Gang Xu Chunbo Chen Huafeng Liu Yongjun Shi Yan Zha Yaozhong Kong Guobin Su Ying Tang Mengchun Gong Linong Ji Fan Fan Hou Jianping Weng Department of Endocrinology First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHeifeiChina Institute of Public Health Sciences Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiChina Division of Nephrology National Clinical Research Center for Kidney DiseaseState Key Laboratory of Organ Failure ResearchNanfang HospitalSouthern Medical UniversityGuangzhouChina Department of Nephrology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina The Second Affiliated Hospital of Zhejiang University School of Medicine HangzhouChina Sir Run Run Shaw Hospital Zhejiang University School of MedicineHangzhouChina Department of Nephrology Sun Yat-Sen Memorial HospitalSun Yat-Sen UniversityGuangzhouChina The Second People’s Hospital of Shenzhen Shenzhen UniversityShenzhenChina Institute of Nephrology Zhongda HospitalSoutheast University School of MedicineNanjingChina Children’s Hospital of Fudan University ShanghaiChina Renal Department and Institute of Nephrology Sichuan Provincial People’s HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaSichuan Clinical Research Center for Kidney DiseasesChengduChina Division of Nephrology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Department of Critical Care Medicine Maoming People’s HospitalMaomingChina key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City Institute of NephrologyAffiliated Hospital of Guangdong Medical UniversityZhanjiangChina Huizhou Central People’s Hospital Sun Yat-Sen UniversityHuizhouChina Guizhou Provincial People’s Hospital Guizhou UniversityGuiyangChina Department of Nephrology the First People’s Hospital of FoshanFoshanChina Department of Nephrology Guangdong Provincial Hospital of Chinese Medicinethe Second Affiliated Hospitalthe Second Clinical CollegeGuangzhou University of Chinese Medicin

Early insulin therapy is capable to achieve glycemic control and restoreβ-cell function in newly diagnosed type 2 diabetes(T2D),but its effect on cardiovascular outcomes in these patients remains *** this nationwide real-world study,we analyzed electronic health record data from 19 medical centers across China between 1 January 2000,and 26 May *** included 5424 eligible patients(mean age 56 years,2176 women/3248 men)who were diagnosed T2D within six months and did not have prior cardiovascular *** Cox regression models were used to estimate the associations of early insulin therapy(defined as the first-line therapy for at least two weeks in newly diagnosed T2D patients)with the incidence of major cardiovascular events including coronary heart disease(CHD),stroke,and hospitalization for heart failure(HF).During 17,158 persons years of observation,we documented 834 incident CHD cases,719 stroke cases,and 230 hospitalized cases for *** diagnosed T2D patients who received early insulin therapy,compared with those who did not receive such treatment,had 31%lower risk of incident stroke,and 28%lower risk of hospitalization for *** significant difference in the risk of CHD was *** found similar results when repeating the aforesaid analysis in a propensity-score matched population of 4578 patients and with inverse probability of treatment weighting *** findings suggest that early insulin therapy in newly diagnosed T2D may have cardiovascular benefits by reducing the risk of incident stroke and hospitalization for HF.

关键词： cardiovascular treatment nationwide

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Acupoint catgut-embedding therapy ameliorates DNCB-induced atopic dermatitis in BALB/c mice by regulating Th2 type immune response and reducing infiltration of CD4^(+)and CD8^(+)cells

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Traditional Medicine Research 2024年第9期9卷 14-20页

作者： Cheng Qin Xiang-Yi Kong Fang Wang Jin Xu Zhuo Zhang Xue-Song Yang Jian-Zhou Ye College of First clinical Medicine Yunnan University of Traditional Chinese MedicineKunming 650500China Yunnan key Laboratory of Dai and Yi Medicines Yunnan University of Chinese MedicineKunming 650500China Yunnan Provincial key Laboratory of Molecular Biology for Sinomedicine Yunnan University of Chinese MedicineKunming 650500China Department of Dermatology The First Affiliated Hospital of Yunnan University of Traditional Chinese MedicineKunming 650021China

Background:This study aimed to assess how acupoint catgut-embedding therapy influences Th2-type immune response and the infiltration of CD4^(+)and CD8^(+)cells in DNCB-induced atopic dermatitis in BALB/c *** also conducted an initial examination of the underlying molecular ***:Seventy-two mice were randomly divided into four groups:normal control,DNCB-induced atopic dermatitis model(AD),AD with acupoint catgut-embedding treatment(ADA),and AD with sham-acupoint catgut-embedding *** DNCB challenge to induce AD,the ADA group received acupoint catgut-embedding therapy treatment at Zusanli(ST 36)and Quchi(LI 11)acupoints every other week from day *** in the AD with sham-acupoint catgut-embedding treatment group underwent the same procedure as the ADA group but without catgut *** was assessed using SCORAD on treatment days 1,10,and *** day 18,nine mice per group were euthanized,and the remaining on day *** changes were observed using hematoxylin-eosin and immunohistochemistry ***-α,IL-4,IL-6,and IL-13 levels were analyzed by ELISA,and GATA3 and STAT6 protein levels by western ***:After 20 days of acupoint catgut-embedding therapy treatment,mice showed reduced dermatitis scores compared to DNCB-induced AD-like *** decreases occurred in serum IL-4,IL-6,IL-13,and TNF-α*** analysis revealed marked reductions in CD4^(+)and CD8^(+)cell infiltration,as well as GATA3 and STAT6 protein ***:Acupoint catgut-embedding therapy may effectively alleviate atopic dermatitis by suppressing Th2 immune responses via the STAT6-GATA3 pathway and reducing CD4^(+)and CD8^(+)T cell infiltration in skin lesions.

关键词： atopic dermatitis acupoint catgut-embedding therapy Th2 type immune response

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