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雷珠单抗辅助微创玻璃体切割术治疗严重PDR的临床研究 被引量:13
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作者 黄玲 徐金华 林琳 《国际眼科杂志》 CAS 北大核心 2018年第8期1511-1514,共4页
目的:观察雷珠单抗(Ranibizumab)辅助微创玻璃体切割术(pars plana vitrectomy,PPV)治疗严重增生性糖尿病视网膜病变(proliferative diabetic retinopathy,PDR)的临床疗效。方法:选取2014-06/2016-07在我院就诊且行23G/25G微创玻璃体切... 目的:观察雷珠单抗(Ranibizumab)辅助微创玻璃体切割术(pars plana vitrectomy,PPV)治疗严重增生性糖尿病视网膜病变(proliferative diabetic retinopathy,PDR)的临床疗效。方法:选取2014-06/2016-07在我院就诊且行23G/25G微创玻璃体切割治疗的严重PDR患者56例56眼的临床资料进行回顾性分析,将术前5~7d行玻璃体腔注射雷珠单抗(intravitreal injection of ranibizumab,IVR,0.5mg/0.05mL)且联合微创PPV者30眼分为A组,将接受单纯微创PPV者26眼分为B组。统计分析两组患者术眼手术操作持续时间、术中出血情况、术中使用电凝次数、医源性视网膜裂孔发生率和术后最佳矫正视力(best corrected visual acuity,BCVA)的差异。术后随访6mo。结果:A组患者手术时间明显短于B组,两组比较差异有统计学意义(98.10±14.23min vs 113.89±17.66min,t=3.703,P=0.0005)。术中A组患者出血眼数明显少于B组,两组比较差异有统计学意义(20%vs 54%,χ~2=6.95,P=0.0084)。A组患者术中平均使用电凝次数明显少于B组,两组比较差异有统计学意义(1.30±1.15次vs 2.73±1.71次,t=3.72,P=0.001)。术中A组患者医源性视网膜裂孔发生率明显少于B组,两组比较差异有统计学意义(7%vs 27%,χ~2=4.24,P=0.0396)。术后1mo时A组BCVA提高率较B组高,但两组比较差异无统计学意义(87%vs 73%,χ~2=1.630,P=0.202)。结论:雷珠单抗辅助微创玻璃体切割术治疗严重PDR可降低术中出血,减少术中电凝使用次数,明显缩短手术时间,减少医源性视网膜裂孔的发生率,而术后最佳矫正视力提高率与单纯微创玻璃体切割术组比较无明显差异。 展开更多
关键词 雷珠单抗 增生性糖尿病视网膜病变 玻璃体切割术
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Induction of apoptosis in human liver carcinoma HepG2 cell line by 5-allyl-7-gen-difluoromethylenechrysin 被引量:10
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作者 Xiang-Wen Tan Hong Xia +1 位作者 jin-hua xu Jian-Guo Cao 《World Journal of Gastroenterology》 SCIE CAS CSCD 2009年第18期2234-2239,共6页
AIM: To investigate the effect of 5-allyl-7-gen-difluoromethylenechrysin (ADFMChR) on apoptosis of human liver carcinoma HepG2 cell line and the molecular mechanisms involved.METHODS: HepG2 cells and L-02 cells we... AIM: To investigate the effect of 5-allyl-7-gen-difluoromethylenechrysin (ADFMChR) on apoptosis of human liver carcinoma HepG2 cell line and the molecular mechanisms involved.METHODS: HepG2 cells and L-02 cells were cultured in vitro and the inhibitory effect of ADFMChR on their proliferation was measured by MTT assay. The apoptosis of HepG2 cells was determined by flow cytometry (FCM) using propidium iodide (PI) fluorescence staining. DNA ladder bands were observed by DNA agarose gel electrophoresis. The influence of ADFMChR on the proxisome proliferator-activated receptor γ (PPARγ), NF-κB, Bcl-2 and Bax protein expression of HepG2 cells were analyzed by Western blotting.RESULTS: MTT assay showed that ADFMChR significantly inhibited proliferation of HepG2 cells in a dose- dependent manner, with little effect on growth of L-02 cells, and when ICs0 was measured as 8.45 μmol/L and 191.55 μmol/L respectively, the potency of ADFMChR to HepG2 cells, was found to be similar to 5-fluorouracil (5-FU, ICso was 9.27 μmol/L). The selective index of ADFMChR cytotoxicity to HepG2 cells was 22.67 (191.55/8.45), higher than 5-FU (SI was 7.05 (65.37/9.27). FCM with PI staining demonstrated that the apoptosis rates of HepG2 cells treated with 3.0, 10.0 and 30.0 μmol/L ADFMChR for 48 h were 5.79%, 9.29% and 37.8%, respectively, and were significantly higher when treated with 30.0 μmol/L ADFMChR than when treated with 30.0 μmol/L ChR (16.0%) (P 〈 0.05) and were similar to those obtained with 30.0 μmol/L 5-FU(41.0%). DNA agarose gel electrophoresis showed that treatment of HepG2 cells with 10.0 μmol/L ADFMChR for 48 h and 72 h resulted in typical DNA ladders which could be reversed by 10.00 pmol/1 GW9662, a blocker of PPARy. Western blotting analysis revealed that aEer 24 h of treatment with 3.0, 10.0, 30.0 μmol/L ADFMChR, PPARy and Bax protein expression in HepG2 cells increased but Bcl-2 and NF-κB expression decreased; however, pre-incubation with 10.0 μmol/L GW9662 could efficiently antagonize and weaken the regulatory effect of 3.0, 30.0 μmol/L ADFMChR on PPARy and NF-KB protein expression in HepG2 cells.CONCLUSION: ADFMChR induces apoptosis of HepG2 cell lines by activating PPARγ, inhibiting protein expression of Bcl-2 and NF-κB, and increasing Bax expression. 展开更多
关键词 Liver neoplasm CHRYSIN 5-allyl-7-gen-difluoromethylenechrysin APOPTOSIS Proxisome prolif-erator-activated receptor γ
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Clinical Features of Adult/Adolescent Atopic Dermatitis and Chinese Criteria for Atopic Dermatitis 被引量:83
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作者 Ping Liu Yan Zhao +24 位作者 Zhang-Lei Mu Qian-Jin Lu Qian-Jin L U Li Zhang xu Yao Min Zheng Yi-Wen Tang Xin-Xiano Lu Xiu-Juan xia You-Kun Lin Yu-Zhen Li Cai-Xia Tu Zhi-Rong Yao jin-hua xu Wei Li Wei Lai Hui-Min Yang Hong-Fu Xie Xiu-Ping Han Zhi-Qiang Xie Xiang Nong Zai-Pei Guo Dan-Qi Deng Tong-Xin Shi Jian-Zhong Zhang 《Chinese Medical Journal》 SCIE CAS CSCD 2016年第7期757-762,共6页
Background: Atopic dermatitis (AD) is an inflammatory skin disease characterized by chronic recurrent dermatitis with profound itching. Most patients have personal and/or family history of atopic diseases. Several ... Background: Atopic dermatitis (AD) is an inflammatory skin disease characterized by chronic recurrent dermatitis with profound itching. Most patients have personal and/or family history of atopic diseases. Several criteria have been proposed for the diagnosis of AD. Although the clinical features of childhood AD have been widely studied, there has been less large-scale study on adult/adolescent AD. The aim of this study was to investigate the clinical features of adult/adolescent patients with chronic symmetrical eczemaJAD and to propose Chinese diagnostic criteria for adult/adolescent AD. Methods: A hospital-based study was performed. Forty-two dermatological centers participated in this study. Adult and adolescent patients (12 years and over) with chronic symmetrical eczema or AD were included in this study. Questionnaires were completed by both patients and-investigators. The valid questionnaires were analyzed using EpiData 3.1 and SPSS 17.0 software. Results: A total of 2662 valid questionnaires were collected (1369 male and 1293 female). Of all 2662 patients, 2062 (77.5%) patients had the disease after 12 years old, while only 600 (22.5%) patients had the disease before 12 years old, suggesting late-onset eczema/AD is common. Two thousand one hundred and thirty-nine (80.4%) patients had the disease for more than 6 months. One thousand one hundred and forty-four (43.0%) patients had a personal and/or family history of atopic diseases. One thousand five hundred and forty-eight (58.2%) patients had an elevated total serum IgE and/or eosinophilia and/or positive allergen-specific IgE. Based on these clinical and laboratory features, we proposed Chinese criteria for adult/adolescent AD. Of all 2662 patients, 60.3% were satisfied with our criteria, while only 48.2% satisfied with Hanifin Rajka criteria and 32.7% satisfied with Williams criteria, suggesting a good sensitivity of our criteria in adult/adolescent AD patients. Conclusion: Late-onset of eczema or AD is common. The clinical manifestations of AD are heterogeneous. We have proposed Chinese diagnostic criteria for adolescent and adult AD, which are simple and sensitive for diagnosis of adult/adolescent AD. 展开更多
关键词 Adolescents and Adults Atopic Dermatitis Clinical Features Diagnostic Criteria ECZEMA
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Secukinumab demonstrates high efficacy and a favorable safety profile over 52 weeks in Chinese patients with moderate to severe plaque psoriasis 被引量:22
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作者 Lin Cai Jian-Zhong Zhang +21 位作者 xu Yao Jun Gu Quan-Zhong Liu Min Zheng Shi-Fa Zhang jin-hua xu Cheng-Xin Li Hao Cheng Qing Guo Wei-Li Pan Shen-Qiu Li Ruo-Yu Li Zai-Pei Guo Zhi-Qi Song Shan-Shan Li Xiu-Qin Dong Linda Wang Rong Fu Pascaline Regnault Pascal Charef Ratal Mazur Manmath Patekar 《Chinese Medical Journal》 SCIE CAS CSCD 2020年第22期2665-2673,共9页
Background:Psoriasis is a chronic inflammatory skin disease,affecting about 0.6%of the Chinese population.Many patients are not well controlled by conventional treatments,thus there is need for new treatment regimens.... Background:Psoriasis is a chronic inflammatory skin disease,affecting about 0.6%of the Chinese population.Many patients are not well controlled by conventional treatments,thus there is need for new treatment regimens.In this study,we assessed the efficacy and safety of secukinumab in Chinese patients with moderate to severe plaque psoriasis.Methods:This study was a 52-week,multicentre,randomized,double-blind,placebo-controlled,parallel-group,Phase 3 trial.A sub-population of study participants(≥18 years)of Chinese ethnicity were randomized to receive subcutaneous injections of 300 or 150 mg secukinumab,or placebo.The co-primary endpoints were psoriasis area severity index(PASI)75 and Investigator’s Global Assessment(IGA)0/1 at Week 12.Results:A total of 441 Chinese patients were enrolled in this study.Co-primary outcomes were achieved;300 and 150 mg secukinumab were superior to placebo as shown in the proportion of patients that achieved PASI 75(97.7%and 87.2%vs.3.7%,respectively;P<0.001),and IGA 0/1(82.3%and 69.7%vs.2.7%;P<0.001)at Week 12.Treatment efficacy was maintained until Week 52.There was no increase in overall adverse events with secukinumab relative to placebo throughout the 52-week period.Conclusion:Secukinumab is highly effective and well tolerated in Chinese patients with moderate to severe plaque psoriasis. 展开更多
关键词 Chinese PSORIASIS IL-17 DERMATOLOGY Clinical trial PASI
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A double-blind,randomized,placebo-and positive-controlled phase III trial of 1% benvitimod cream in mild-to-moderate plaque psoriasis 被引量:14
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作者 Lin Cai Gen-Hui Chen +23 位作者 Qian-Jin Lu Min Zheng Yu-Zhen Li Jin Chen Jie Zheng Fu-Ren Zhang Jian-Bin Yu Sen Yang Fu-Qiu Li Sheng-Xiang Xiao Qiu-Ning Sun jin-hua xu Xing-Hua Gao Hong Fang Tian-Wen Gao Fei Hao Quan-Zhong Liu Ya-Ting Tu Ruo-Yu Li Bao-Xi Wang Dan-Qi Deng Qing-Shan Zheng Hong-Xia Liu Jian-Zhong Zhang 《Chinese Medical Journal》 SCIE CAS CSCD 2020年第24期2905-2909,共5页
Background:Benvitimod cream,a novel synthetic small molecule,was effective in treating mild-to-moderate plaque psoriasis.We conducted a phase III clinical trial to assess the efficacy and safety of benvitimod cream in... Background:Benvitimod cream,a novel synthetic small molecule,was effective in treating mild-to-moderate plaque psoriasis.We conducted a phase III clinical trial to assess the efficacy and safety of benvitimod cream in patients with mild-to-moderate plaque psoriasis.Methods:We randomly assigned 686 patients(2:1:1)to receive 1%benvitimod cream,0.005%calcipotriol ointment or placebo twice a day for 12 weeks.The primary efficacy end points were the percentage of patients with a 75%or greater reduction from baseline in the psoriasis area and severity index(PASI 75)score and with a score of 0 or 1 in static physician’s global assessment(sPGA)at week 12.Results:The results showed that 50.4%of patients in the benvitimod group achieved PASI 75,which was significantly higher than that in the calcipotriol(38.5%,P<0.05)and placebo(13.9%,P<0.05)groups.The proportion of patients achieving an sPGA score 0 or 1 was 66.3%in the benvitimod group and 63.9%in the calcipotriol group,which were both significantly higher than that in the placebo group(34%,P<0.05).In the long-term follow-up study,50.8%of patients experienced recurrence.After retreatment with 1%benvitimod,73.3%of patients achieved an sPGA score of 0 or 1 again at week 52.Adverse events included application site irritation,follicular papules,and contact dermatitis.No systemic adverse reactions were reported.Conclusion:During this 12-week study,benvitimod cream was demonstrated with high effectiveness and safety in patients with mild-to-moderate plaque psoriasis. 展开更多
关键词 PSORIASIS Benvitimod Immune modulator Drug discovery 3 5-dihydroxy-4-isopropylstilbene
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Consensus by Chinese Expert Panel on Chlamydia trachomatis-Resistant and Chlamydia trachomatis-Persistent Infection 被引量:8
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作者 Man-Li Qi Yuan-Li Guo +18 位作者 Qian-Qiu Wang Xiang-Sheng Chen Jian-De Han Xiao-Hong Su Wen-Hui Lun Hao Cheng jin-hua xu Hong-Qing Tian Li Che Zhi-Yuan Ya Wen-Li Feng Juan Jiang Ping-Yu Zhou Xian-Biao Zo Hong-Hui xu Wei-Min Shi Jun Liu Lin Zhu Quan-Zhong Liu 《Chinese Medical Journal》 SCIE CAS CSCD 2017年第23期2852-2856,共5页
Chlamydia trachomatis (Ct) genital infection is the most common sexually transmitted disease (STD) in China and the US. The morbidity of Ct genital infection in China has increased from 32.48/100,000 in 2008 to 37... Chlamydia trachomatis (Ct) genital infection is the most common sexually transmitted disease (STD) in China and the US. The morbidity of Ct genital infection in China has increased from 32.48/100,000 in 2008 to 37.18/100,000 in 2015.[1] The major areas of Ct infections are concentrated in the Zhujiang Delta, Changjiang Delta, Minjiang Area, and West China. In these areas, the highest incidence of Ct infection reaches 615.99/100,000 citizens. In the US, there are 1,441,789 reported Ct, which include 627.2 females and 278.4 males per 100,000 population. It is now the most prevalent STD, with its rate increasing to 22% in males and 6% in females.[2] Ct genital infection can cause epididymitis, prostatitis, cervicitis, annexitis, infertility, and atopic pregnancy, which have been identified as the major public health problems. 展开更多
关键词 Chlamydia trachomatis Persistent Infection Therapy Resistant
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2019 Chinese expert consensus statement on diagnosis and treatment of syphilis 被引量:2
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作者 Qian-Qiu Wang +18 位作者 Rui-Li Zhang Yue-Ping Yin Quan-Zhong Liu Shu-Zhen Qi Dong-Mei xu Yu-Ye Li Xiao-Fang Li Xiao-Hong Su Min-Zhi Wu Xian-Biao Zou Li-Gang Yang Xiang-Sheng Chen Ping-Yu Zhou jin-hua xu Xiang-Dong Gong Guo-Jun Liang Juan Jiang Hao Cheng Feng-Qin Ge 《Chinese Medical Journal》 SCIE CAS CSCD 2020年第19期2335-2337,共3页
Syphilis,caused by Treponema pallidum subsp pallidum(T.pallidum),is a chronic,systemic human disease transmitted through sexual contact.The incidence and prevalence of syphilis is still high in China.[1]To guide the p... Syphilis,caused by Treponema pallidum subsp pallidum(T.pallidum),is a chronic,systemic human disease transmitted through sexual contact.The incidence and prevalence of syphilis is still high in China.[1]To guide the prevention measures and management of this disease,we renew the guidelines on diagnosis and treatment of syphilis[Supplementary file,http://links.lww.com/CM9/A292].Manifestations and diagnosis of all stages of syphilis are presented in Table 1,and management in Table 2. 展开更多
关键词 DIAGNOSIS PREVENTION TREATMENT
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National Guidelines on Diagnosis and Treatment of Gonorrhea in China (2020) 被引量:2
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作者 Qian-Qiu Wang Rui-Li Zhang +20 位作者 Quan-Zhong Liu jin-hua xu Xiao-Hong Su Yue-Ping Yin Shu-Zhen Qi Dong-Mei xu Ping-Yu Zhou Yu-Ye Li Xiao-Fang Li Min-Zhi Wu Xian-Biao Zou Li-Gang Yang Xiang-Sheng Chen Xiang-Dong Gong Guo-Jun Liang Juan Jiang Hao Cheng Feng-Qin Ge National Center for STD Control,Chinese Centers for Disease Control and Prevention Committee of STD,Branch of Dermatovenereology,Chinese Medical Association Committee of STD,Chinese Dermatologist Association 《International Journal of Dermatology and Venereology》 2020年第3期129-134,共6页
Gonorrhea is one of the main sexually transmitted diseases in China.It mainly affects the genitourinary tract,and its clinical manifestations vary from asymptomatic to complicated types.The diagnosis of gonorrhea shou... Gonorrhea is one of the main sexually transmitted diseases in China.It mainly affects the genitourinary tract,and its clinical manifestations vary from asymptomatic to complicated types.The diagnosis of gonorrhea should be based on the patient's epidemiologicai history,clinical manifestations,and laboratory examination results.Treatment should be prompt and standardized and should involve the recommended treatment regimens.Patients should be appropriately followed up after treatment.The antimicrobial resistance of gonococcal isolates has become a severe problem of clinical concern.In order to provide technical guidance of the diagnosis and treatment of gonorrhea for health care workers,the authors developed the guidelines based on the version of 2014,which will be of important in the standardizing medical care of gonorrhea,and further facilitating control and prevention of the disease. 展开更多
关键词 GONORRHEA DIAGNOSIS TREATMENT GUIDELINES
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Chinese Guidelines for the Diagnosis and Treatment of Urticaria:2018 Update 被引量:1
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作者 Center for Urticaria Research,Chinese Society of Dermatology jin-hua xu +1 位作者 Hui Tang Fei Hao 《International Journal of Dermatology and Venereology》 2020年第1期8-13,共6页
Urticaria is a common dermatological condition that is characterized by wheals and pruritus.Certain types of urticaria can be resistant to treatment,and recurrence is common.These guidelines supplement and improve upo... Urticaria is a common dermatological condition that is characterized by wheals and pruritus.Certain types of urticaria can be resistant to treatment,and recurrence is common.These guidelines supplement and improve upon the previous version(published in 2014)of the Guidelines for the Diagnosis and Treatment of Urticaria in China,and incorporate recent research advances in urticaria.These guidelines are suitable for both Chinese adults and children of Han nationality with urticaria.These guidelines update and broaden the definition,pathogenesis,classification,diagnosis,and treatment of urticaria,and serve as a scientific and authoritative reference for the diagnosis and management of urticaria. 展开更多
关键词 URTICARIA GUIDELINES DIAGNOSIS THERAPY management
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Diagnosis and Treatment of Acne Inversa/Hidradenitis Suppurativa in China: An Expert Consensus Statement (2021 Version)
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作者 Hong Fang Xing-Hua Gao +24 位作者 Song-Mei Geng Heng Gu Jun Gu Li He Xian Jiang Hong-Zhong Jin Qiang Ju Xiao-Jing Kang Wei Lai Cheng-Xin Li Hang Li Heng-Jin Li Shan-Shan Li Yu-Zhen Li Qing Sun Juan Tao Baoxi Wang Gang Wang Xin-Feng Wu Lei-Hong Xiang Hong-Fu Xie Hao-Xiang xu jin-hua xu Yan Yan Zhi-Zhong Zheng 《International Journal of Dermatology and Venereology》 2021年第2期100-108,共9页
Acne inversa/hidradenitis suppurativa is a chronic,recurrent,inflammatory skin disease that affects the pilosebaceous units,causinfollicular occlusion.The etiology and pathogenesis of acne inversa/hidradenitis suppura... Acne inversa/hidradenitis suppurativa is a chronic,recurrent,inflammatory skin disease that affects the pilosebaceous units,causinfollicular occlusion.The etiology and pathogenesis of acne inversa/hidradenitis suppurativa involves internal and external factors such as genetic susceptibility,inflammation and immunity,microorganisms,obesity,and smoking.acne inversa/hidradenitis suppurativa is difficult to treat,and the current aim of treatment is to control the frequency and duration of disease flares and improve the quality of life.Treatment protocols for acne inversa/hidradenitis suppurativa should be selected based on the disease severity grade.Medical treatments include antibiotics,retinoids,biologics,immunosuppressive agents,and antiandrogen agents.Adjuvant treatments include surgery and laser/light therapies.This consensus aims to further standardize the diagnosis and treatment procedures of acne inversa/hidradenitis suppurativa in China to facilitate its diagnosis and treatment. 展开更多
关键词 acne inversa CONSENSUS DIAGNOSIS hidradenitis suppurativa THERAPY
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Chinese Expert Consensus on Clinical Application of Patch Test (Revised 2020)
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作者 Bang-Tao Chen Fei Hao +19 位作者 Hong Fang Heng Gu Hong-Zhong Jin Wei Lai Cheng-Xin Li Lin-Feng Li Wei Liu Yan Lu Xin Shi Juan Tao Gang Wang Li-Ping Wen Ting Xiao jin-hua xu Fu-Ren Zhang Li-Tao Zhang Zuo-Tao Zhao Hua Zhong Ying Zou The Allergic Disease Committee of Chinese Dermatologist Association 《International Journal of Dermatology and Venereology》 2020年第3期142-147,共6页
Allergic contact dermatitis is a common clinical allergic disease.The patch test is the gold standard for finding and clarifying contact allergens.With the deepening understanding of the epidemiology,pathogenesis,and ... Allergic contact dermatitis is a common clinical allergic disease.The patch test is the gold standard for finding and clarifying contact allergens.With the deepening understanding of the epidemiology,pathogenesis,and clinical manifestations of contact dermatitis,as well as the increased requirements for the standardized application of patch tests,the relevant consensus needs to be continuously updated.This consensus is updated on the basis of the version issued in 2015.In this revised version,it refines the selection of clinical indications,improves the judgment end interpretation of results,adds delayed detection and patient education,and so on,which aims to further standardize clinical applications and improve the value of patch test. 展开更多
关键词 allergens allergic contact dermatitis CHINESE expert consensus patch tests
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SOX4 Mediates BRAF Inhibitor Resistance in Melanoma through Regulation of IGF-1R Signaling: In Vitro Study
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作者 Xiao Liu Jun Mi +6 位作者 Hai-Hong Qin Shan He Zheng Li Jing-Xiu Chai Ming Li jin-hua xu Jin-Feng Wu 《International Journal of Dermatology and Venereology》 2020年第3期156-165,共10页
Objective:SOX4,a transcription factor,has been found to contribute to tumorigenesis in several cancers.This study was performed to determine whether SOX4 mediates BRAF inhibitor resistance in melanoma.Methods:Melanoma... Objective:SOX4,a transcription factor,has been found to contribute to tumorigenesis in several cancers.This study was performed to determine whether SOX4 mediates BRAF inhibitor resistance in melanoma.Methods:Melanoma cell lines with acquired resistance to BRAF inhibitor(SK-MEL-5R,SK-MEL-28R,and A375R)were generated by adding escalating concentrations of PLX4032 into parental SK-MEL-5,SK-MEL-28,and A375 cells for>6 months.The expression of SOX4 and insulin-like growth factor 1 receptor(IGF-1R)was measured by quantitative real-time polymerase chain reaction(qRT-PCR)and Westem blotting.The downstream signaling of IGF-1R was detected by Westem blotting.SOX4 and IGF-1R overexpression or knockdown was conducted by lentivirus transfection.Cell viability and apoptosis were demonstrated by MTT and flow cytometry,respectively.The binding ability of SOX4 to IGF-1R promoter was determined by chromatin immunoprecipitation quantitative PCR assay.Results:SOX4 was upregulated in BRAF inhibitor-resistant melanoma cells as compared with parental cells(SK-MEL-5 group,1.02 vs.6.33;SK-MEL-28 group,1.03 vs.3.22;A375 group,1.00 vs.1.86;t=°7.069,29.26,and 5.291,respectively;all P<0.01),and PLX4032 treatment could not alter the expression of SOX4 in resistant cells.SOX4 overexpreesion attenuated the response of parental cells to PLX4032(for cell viability,SK-MEL-5 group:77.76%vs.104.28%,F=91.50;SK-MEL-28 group:60.59%vs.93.13%,F=171.8;A375 group:62.50%vs.80.87%,F=47.15.For apoptosis rates,SK-MEL-5 group:34.90%vs.14.31%,F=4.781;SK-MEL-28 group,40.8%vs.29.4%,F=13.32,P=0.063;A375 group:40.20%vs.17.09%,F=11.39;all P<0.05,otherwise indicated).While SOX4 knockdown enhanced the response of resistant cells to PLX4032(for cell viability,SK-MEL-5R group:93.75%vs.69.53%,F=94.45,SK-MEL-28R group:95.60%vs.66.79%,F=30.41,A375R group:95.51%vs.59.98%,F=111.6;for apoptosis rates,SK-MEL-5R group:16.2%vs.44.4%,F=25.67,SK-MEL-28R group:26.59%vs.44.20%,F=158.0,A375R group:5.98%vs.31.51%,F=14.35,and all P<0.01).Chromatin immunoprecipitation quantitative PCR assay demonstrated that SOX4 binded to the promoter of IGF-1R(1.04 vs.1.94[-1044 to-920 bp]and 0.110 vs.0.139[GAPDH],F=534.5,P<0.01).In addition,SOX4 overexpression increased IGF-1R end its downstream phosphorylated ERK,phosphorylated AKT,and phosphorylated STAT3 expression,while SOX4 knockdown exerted the opposite effects.Moreover,IGF-1R knockdown overcame SOX4 overexpreesion-induced PLX4032 resistance(cell viability:35.85%vs.52.79%vs.37.84%[A375 group,negative control group vs.SOX4 overexpressing group vs.SOX4 overexpressing+sh-IGF-1R group];apoptosis rates:25.30%vs.9.56%vs.22.26[A375 group,negative control group vs.SOX4 overexprassing group vs.SOX4 overexpressing+sh-IGF-1R group];F=13.01 and 41.87,respectively;all P<0.01),while IGF-1R overexpression abrogated SOX4 knockdown-induced response enhancement to PLX4032 for comparison of negative control group,sh-SOX4group and sh-SOX4+IGF-1 R overexpreesing group(cell viability:96.62%vs.86.86%vs.97.26%(A375R),98.15%vs.81.63%vs.98.49%[SK-MEL-5R];apoptosis rates:13.81%vs.32.00%vs.12.16[A375R],29.70%vs.41.40%vs.26.10%[SK-MEL-5R];F=13.56,12.86,38.81,and Conclusion:SOX4 mediates BRAF inhibitor resistance in melanoma through regulation of IGF-1R signaling.SOX4 might serve as a potential target for the treatment of BRAF inhibitor-resistant melanoma.39.85,respectively;all P<0.01). 展开更多
关键词 SOX4 MELANOMA BRAF inhibitor drug resistance IGF-1R
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