Artificial intelligence in dermatology: past, present, and future

Artificial intelligence (AI) had been first coined at a famous Dartmouth College conference in 1956. AI is gradually interrelated with all disciplines, and also permeates all aspects of the medical field. In the early 1970s, medical researchers discovered the applicability of AI in life sciences.[1] AI can play a role in many aspects, such as medical image recognition and auxiliary diagnosis,[2] biotechnology,[3] drug research and development,[4] etc. Currently, medical image recognition is the most widely used.

Molecular Epidemiological Study on Prevalence of Human Papillomaviruses in Patients with Common Warts in Beijing Area

Objective To study the circulation, distribution, and genomic diversity of HPVs in common warts in Beijing area of China. Methods Forty eight patients with pathologically diagnosed common warts were screened for the presence of HPV with HPV type-specific PCR and direct sequencing analysis. The genomic diversity of HPVs prevalent in Chinese patients was analyzed based on LCR. Results Forty one （85.5%） samples were positive for HPV DNA, 13（31.7%）-HPV-57, 12（29.3%）-HPV-la, 7（17%）-HPV-27 and 5（12.2%）-HPV-2a. Four cases were infected with two different HPV types, two （4.9%） with HPV-la and HPV-27, one （2.4%） with HPV-1 and HPV-57 and one （2.4%） with HPV-27 and HPV-57. In contrast to the prevalence of single strain of novel HPV-57 variant and HPV-1 prototype, two HPV-2 and three HPV-27 novel variants were found to circulate in Beijing. Conclusion HPV-1, -2, -27 and -57 are predominantly prevalent in patients with common warts in Beijing.

Construction of an artificial intelligence system in dermatology: effectiveness and consideration of Chinese Skin Image Database (CSID)

After more than 60 years of development,artificial intelligence(AI)has been widely used in various fields.Especially in recent years,with the development of deep learning,AI has made many remarkable achievements in the medical field.Dermatology,as a clinical discipline with morphology as its main feature,is particularly suitable for the development of AI.The rapid development of skin imaging technology has helped dermatologists to assist in the diagnosis of diseases and has greatly improved the accuracy of diagnosis.Skin imaging data have natural big data attributes,which is important for AI research.The establishment of the Chinese Skin Image Database(CSID)has solved many problems such as isolated data islands and inconsistent data quality.Based on the CSID,many pioneering achievements have been made in the research and development of AI-assisted decision-making software,the establishment of expert organizations,personnel training,scientific research,and so on.At present,there are still many problems with AI in the field of dermatology,such as clinical validation,medical device licensing,interdisciplinary,and standard formulation,which urgently need to be solved by joint efforts of all parties.

Present status and prospect of skin imaging equipment in some public hospitals in China

To the Editor:The continuous development and maturity of imaging science and technology have made skin imaging one of the essential subspecialties of dermatology.This has had an objective and comprehensive impact in changing the dermatology diagnosis mode.Thus,skin imaging has become one of the diagnostic skills that all dermatologists must master.Skin imaging equipment plays a crucial role in clinical and scientific research.It is not only a necessary aid to correct diagnose of skin diseases,but also a crucial link and hardware foundation for skin imaging capacity strengthening.Dermoscopy,reflectance confocal microscopy(RCM)and very high frequency(VHF)skin ultrasound imaging diagnostic system(VHF skin ultra-sound)have become skin imaging equipments commonly used in Chinese dermatological practice.In recent years,with the growing emphasis on dermatology in hospitals at all levels,investment in medical equipment has been increasing and skin imaging equipment has been continuously optimized.As far as we know,there is no literature report on the skin imaging equipment current status in Chinese public hospitals.This study intended to investigate and analyze the current status of skin imaging equipment in the country,and to provide an objective basis for further standardizing and strengthening the development of skin imaging equipment and dermatology construction.In this way,it is expected to lay the foundations to meet clinical needs and achieve the optimal allocation of medical resources.

COMPARISON BETWEEN IMMUNOFLUORESCENCE AND PCR IN DETECTING HUMAN PAPILLOMA VIRUS IN CONDYLOMA ACUMINATA

Objective To compare the effectiveness of immunofluorescence and polymerase chain reaction (PCR) in detecting human papilloma virus (HPV) in condyloma acuminata (CA). Methods HPVs in CA tissues from 60 patients were detected by immunofluorescence and PCR, respectively. Different subtypes of HPVs were also identified with restriction fragment length polymorphism (RFLP). Results The positive detective rates of immunofluorescence and PCR were 56.67% (34/60) and 96.67% (58/60), respectively (P<0.01). RFLP results showed HPV6 and HPV11 were the main subtypes in the detected virus, which accounted for 98.28%. Conclusion The sensibility of PCR is superior to that of immunofluorescence.

Detection of Trichomonas Vaginalis Infection in Male Non-gonococcal Urethritis Patients by InPouch TV Culture and Polymerase Chain Reaction

Objective: To study the prevalence of Trichomonas vaginalis(TV) infection in Chinese male patients with nongonococcal urethritis (NGU), to evaluate the sensitivity and specificity of urine-based and urethral swab polymerase chain reaction(PCR) detection, to set up a method for non-invasive detection of male TV infection. Method: One hundred and five male NGU patients were selected from a Beijing STD clinic. Two urethral swabs were obtained from each patient, one for the InPouch TV culturesystem and the other for PCR. In addition, one first void urinespecimen was collected for PCR detection. Culture wasconsidered the “gold standard”. The sensitivity, specificity,positive predictive value (PPV) and negative predictive value(NPV) of the two PCR detections were compared to cultureresults. Results: The prevalence of urine-based PCR and urethralswab PCR detection was 3.81% (4/105) and 4.76% (5/105)respectively. Compared to culture, the sensitivity, specificity,PPV and NPV were 80%, 100%, 100% and 99% for urine-based PCR and 80%, 99%, 80% and 99% for urethral swabPCR. Conclusion: TV is one of the etiological agents in male NGU,with a 4.76% prevalence of infection in our study. The urinebased PCR detection has higher sensitivity and specificity and provides a noninvasive method more feasible in practice.

Non-invasive imaging of pathological scars using a portable handheld two-photon microscope

Background:Pathological scars are a disorder that can lead to various cosmetic,psychological,and functional problems,and no effective assessment methods are currently available.Assessment and treatment of pathological scars are based on cutaneous manifestations.A two-photon microscope(TPM)with the potential for real-time non-invasive assessment may help determine the under-surface pathophysiological conditions in vivo.This study used a portable handheld TPM to image epidermal cells and dermal collagen structures in pathological scars and normal skin in vivo to evaluate the effectiveness of treatment in scar patients.Methods:Fifteen patients with pathological scars and three healthy controls were recruited.Imaging was performed using a portable handheld TPM.Five indexes were extracted from two dimensional(2D)and three dimensional(3D)perspectives,including collagen depth,dermo-epidermal junction(DEJ)contour ratio,thickness,orientation,and occupation(proportion of collagen fibers in the field of view)of collagen.Two depth-dependent indexes were computed through the 3D second harmonic generation image and three morphology-related indexes from the 2D images.We assessed index differences between scar and normal skin and changes before and after treatment.Results:Pathological scars and normal skin differed markedly regarding the epidermal morphological structure and the spectral characteristics of collagen fibers.Five indexes were employed to distinguish between normal skin and scar tissue.Statistically significant differences were found in average depth(t=9.917,P<0.001),thickness(t=4.037,P<0.001),occupation(t=2.169,P<0.050),orientation of collagen(t=3.669,P<0.001),and the DEJ contour ratio(t=5.105,P<0.001).Conclusions:Use of portable handheld TPM can distinguish collagen from skin tissues;thus,it is more suitable for scar imaging than reflectance confocal microscopy.Thus,a TPM may be an auxiliary tool for scar treatment selection and assessing treatment efficacy.

Assessment of imaging diagnosis ability of skin tumors in Chinese dermatologists

Skin tumors begin from normal skin cells, and some parts of them may transform with the potential to reproduce in an out-of-control manner.[1] Skin tumors are exceedingly common and the incidence is increasing at an alarming rate across the globe.

Trans-ethnic Mendelian randomization study of systemic lupus erythematosus and common female hormone-dependent malignancies

Background:Observational research has reported that systemic lupus erythematosus(SLE)is related to common female hormonedependent cancers,but the underlying causal effect remains undefined.This study aimed to explore the causal association of these conditions by Mendelian randomization(MR)analysis.Methods:We selected instrumental variables for SLE from genome-wide association studies(GWASs)conducted in European and East Asian populations.The genetic variants for female malignant neoplasms were obtained from corresponding ancestry GWASs.We utilized inverse variance weighted(IVW)as the primary analysis,followed by sensitivity analysis.Furthermore,we conducted multivariable MR(MVMR)to estimate direct effects by adjusting for the body mass index and estradiol.Finally,we implemented reverse direction MR analysis and gave a negative example to test the reliability of MR results.Results:We found SLE was significantly negatively associated with overall endometrial cancer risk(odds ratio[OR]=0.961,95%confidence interval[CI]=0.935-0.987,P=3.57E03)and moderately inversely related to endometrioid endometrial cancer(ENEC)(OR=0.965,95%CI=0.936-0.995,P=0.024)risk in the European population by IVW.We replicated these results using other MR models and detected a direct effect by MVMR(overall endometrial cancer,OR=0.962,95%CI=0.941-0.983,P=5.11E04;ENEC,OR=0.964,95%CI=0.940-0.989,P=0.005).Moreover,we revealed that SLE was correlated with decreased breast cancer risk(OR=0.951,95%CI=0.918-0.986,P=0.006)in the East Asian population by IVW,and the effect was still significant inMVMR(OR=0.934,95%CI=0.859-0.976,P=0.002).The statistical powers of positiveMRresults were all>0.9.Conclusion:This finding suggests a possible causal effect of SLE on the risk of overall endometrial cancer and breast cancer in European and East Asian populations,respectively,by MR analysis,which compensates for inherent limitations of observational research.

A Randomized Controlled Trial Comparing Total Glucosides of Paeony Capsule and Compound Glycyrrhizin Tablet for Alopecia Areata

Objective： To observe the efficacy and safety of total glucosides of paeony capsule （TGPC） in patients with mild and moderate alopecia areata. Methods： A total of 86 outpatients were randomly allocated into two groups of TGPC （treatment, 44 cases） and compound glycyrrhizin tablet （control, 42 cases）. The treatment group was given oral TGPC, three times daily and 600 mg per time; the control group was given oral compound glycyrrhizin tablets, three times daily and 50 mg per time. In addition, both groups were given 10 mg of vitamin B2 and tapped the bold patches with massage. The treatment course was three months for both groups. Peripheral blood T-cell subsets （CD3^＋CD4^＋, CD3^＋CD8^＋, Th, Ts, Th/Ts） of 10 patients randomly selected from each group respectively were tested before and after three months of treatment. The effectiveness and adverse reaction of all cases were observed each month. The safety was evaluated according to the incidence rate of adverse reaction. Results： In the treatment group, the cured and markedly effective rate was 36.36% （16/44）, 50.00% （22/44） and 68.18% （30/44） at the end of first, second and third month of treatment, respectively, and the incidence rate of adverse reaction was 13.64% （6/44）. In the control group, the cured and markedly effective rate was 38.10% （16/42）, 57.14% （24/42） and 71.43% （30/42）, respectively, and the incidence rate of adverse reaction was 16.67% （7/42）. The cured and markedly effective rate and the incidence rate of adverse reaction were similar in both groups （P〉0.05）. TGPC and compound glycyrrhizin tablet can inhibit CD3^＋CD4^＋ and CD3^＋CD8^＋, and decrease the ratio of Th/Ts （P〈0.05）. Conclusion： TGPC is effective and safe in the treatment of alopecia areata.

Long-pulse Nd：YAG 1064-nm laser treatment for onychomycosis

Background Recent research shows that lasers can inhibit fungal growth and that Nd：YAG 1064-nm lasers can penetrate as deep as the lower nail plate. The aim of this study was to observe the effect of a long-pulse Nd：YAG 1064-nm laser on 154 nails of 33 patients with clinically and mycologically proven onychomycosis. Methods Thirty-three patients with 154 nails affected by onychomycosis were randomly assigned to two groups, with the 154 nails divided into three sub-groups （Ⅱ degree,Ⅲ degree, and IV degree） according to the Scoring Clinical Index of Onychomycosis. The 15 patients （78 nails） in group 1 were given eight sessions with a one-week interval, and the 18 patients （76 nails） in group 2 were given four sessions with a one-week interval. Results In group 1, the effective rates at 8 weeks, 16 weeks, and 24 weeks were 63%, 62%, and 51%, respectively, and the effective rates in group 2 were 68%, 67%, and 53% respectively. The treatment effect was not significantly different between any sub-group pair （P 〉0.05）. Conclusions Long pulse Nd：YAG 1064-nm laser was effective for onychomycosis. It is a simple and effective method without significant complications or side effects and is expected to become an alternative or replacement therapy for onychomycosis.

Literature Research of Chinese Medicine Recipes for the Treatment of Psoriasis Vulgaris with Blood-heat Syndrome Type

Objective：To analyze and investigate the rules for drug utilization of Chinese medicine for the treatment of psoriasis vulgaris with blood-heat syndrome.Methods：The literatures that met the following inclusion criteria were screened out from China National Knowledge Infrastructure（CNKI） from January 1998 to December 2008,including the compositions and dosages of the recipes reported completely and accurately, the sample size being30 cases and the total effective rate being70%.Results：In total,289 papers meeting the inclusion criteria were retrieved,involving 301 recipes;in which 111 recipes consisting of 145 individual drugs were the function for clearing the heat,accounting for 52.84%.The three drugs with the highest utilized frequency were Radix Rehmanniae,Radix Arnebiae seu Lithospermi and Cortex Moutan.Meridian adscription of the drugs was mainly the Gan（肝）-meridian.Conclusion：There were rules for the treatment of psoriasis vulgaris of blood-heat syndrome with Chinese medicine prescriptions.

Effect of New Pulian Ointment (新普连膏) in Treating Psoriasis of Blood-Heat Syndrome:A Randomized Controlled Trial

Objective:To objectively assess the clinical efficacy and safety of a new Pulian Ointment(新普连膏,NPLO) in treating psoriasis of blood-heat syndrome of Chinese medicine.Methods:A total of 108 patients with psoriasis of blood-heat syndrome were equally assigned,using a randomizing digital table,to the test group treated externally with NPLO and the control group treated with placebo;the medication was done using a single-blinded method twice a day.Meanwhile,all patients received by oral intake a conventional Ch...

Dermoscopy in China: current status and future prospective

Objective: Dermoscopy is a useful technique for improving the diagnostic accuracy of various types of skin disorders. In China, dermoscopy has been widely accepted, and domestic researchers have made tremendous progress in the field of dermoscopy. The main purpose of this review is to summarize the current status of dermoscopy in China and identify its future directions. Data sources: Articles included in this review were obtained by searching the following databases: Wanfang, China National Knowledge Infrastructure, PubMed, and the Web of Science. We focused on research published before 2019 with keywords including dermoscopy, dermoscopic, dermoscope and trichoscopy. Study selection: A total of 50 studies were selected. Of these studies, 20 studies were in Chinese and 30 in English, research samples of all the studies were collected from Chinese populations. Results: Since 2000, more than 380 articles about dermoscopy have been published in domestic or foreign journals. Dermoscopy can improve the diagnostic accuracy of neoplastic diseases, evaluating the therapeutic effect of treatment, and determining the treatment endpoint, and it can also assist in the differential diagnosis of inflammatory diseases and in the assessment of the severity of the disease. In addition, researches about the applications of dermoscopy during surgical treatment have been published. Training courses aiming to improve the diagnostic ability of dermatologists, either face-to-face or online, have been offered. The Chinese Skin Image Database, launched in 2017 as a work platform for dermatologists, has promoted the development of dermoscopy in China. Computer-aided diagnostic systems based on the Chinese population are ready for use. In the future, cooperation, resource sharing, talent development, image management, and computer-aided diagnosis will be important directions for the development of dermoscopy in China. Conclusion: Dermoscopy has been widely used and developed in China, however, it still needs to address more challenges in the future.

Effect of Chinese Herbal Medicine Combined with Acitretin Capsule in Treating Psoriasis of Blood-Heat Syndrome Type

Objective:To observe the clinical curative effect of Chinese herbal medicine combined with acitretin capsule in treating psoriasis of blood-heat syndrome(P-BH).Methods:Eighty patients of P-BH were randomly assigned to two groups,39 in Group A and 41 in Group B.Both was treated with Chinese herbal medicines for clearing heat,cooling blood and removing toxic substance,and acitretin capsule was given to Group A additionally,with 8 weeks as one therapeutic course.The clinical curative effect was compared betwee...

Deficiency of two-pore segment channel 2 contributes to systemic lupus erythematosus via regulation of apoptosis and cell cycle

Background:Systemic lupus erythematosus(SLE)is a complex autoimmune disease,and the mechanism of SLE is yet to be fully elucidated.The aim of this study was to explore the role of two-pore segment channel 2(TPCN2)in SLE pathogenesis.Methods:Quantitative reverse transcription polymerase chain reaction(qRT-PCR)was used to detect the expression ofTPCN2 in SLE.We performed a loss-of-function assay by lentiviral construct in Jurkat and THP-1 cell.Knockdown ofTPCN2 were confirmed at the RNA level by qRT-PCR and protein level by Western blotting.Cell Count Kit-8 and flow cytometry were used to analyze the cell proliferation,apoptosis,and cell cycle ofTPCN2-deficient cells.In addition,gene expression profile ofTPCN2-deficient cells was analyzed by RNA sequencing(RNA-seq).Results:TPCN2 knockdown with short hairpin RNA(shRNA)-mediated lentiviruses inhibited cell proliferation,and induced apoptosis and cell-cycle arrest of G2/M phase in both Jurkat and THP-1 cells.We analyzed the transcriptome of knockdown-TPCN2-Jurkat cells,and screened the differential genes,which were enriched for the G2/M checkpoint,complement,and interleukin-6-Janus kinase-signal transducer and activator of transcription pathways,as well as changes in levels of forkhead box O,phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin,and T cell receptor pathways;moreover,TPCN2 significantly influenced cellular processes and biological regulation.Conclusion:TPCN2 might be a potential protective factor against SLE.

Diagnostic capacity of skin tumor artificial intelligence-assisted decision-making software in real-world clinical settings

Background:Youzhi artificial intelligence(AI)software is the AI-assisted decision-making system for diagnosing skin tumors.The high diagnostic accuracy of Youzhi AI software was previously validated in specific datasets.The objective of this study was to compare the performance of diagnostic capacity between Youzhi AI software and dermatologists in real-world clinical settings.Methods:A total of 106 patients who underwent skin tumor resection in the Dermatology Department of China-Japan Friendship Hospital from July 2017 to June 2019 and were confirmed as skin tumors by pathological biopsy were selected.Dermoscopy and clinical images of 106 patients were diagnosed by Youzhi AI software and dermatologists at different dermoscopy diagnostic levels.The primary outcome was to compare the diagnostic accuracy of the Youzhi AI software with that of dermatologists and that measured in the laboratory using specific data sets.The secondary results included the sensitivity,specificity,positive predictive value,negative predictive value,F-measure,and Matthews correlation coefficient of Youzhi AI software in the real-world.Results:The diagnostic accuracy of Youzhi AI software in real-world clinical settings was lower than that of the laboratory data(P<0.001).The output result of Youzhi AI software has good stability after several tests.Youzhi AI software diagnosed benign and malignant diseases by recognizing dermoscopic images and diagnosed disease types with higher diagnostic accuracy than by recognizing clinical images(P=0.008,P=0.016,respectively).Compared with dermatologists,Youzhi AI software was more accurate in the diagnosis of skin tumor types through the recognition of dermoscopic images(P=0.01).By evaluating the diagnostic performance of dermatologists under different modes,the diagnostic accuracy of dermatologists in diagnosing disease types by matching dermoscopic and clinical images was significantly higher than that by identifying dermoscopic and clinical images in random sequence(P=0.022).The diagnostic accuracy of dermatologists in the diagnosis of benign and malignant diseases by recognizing dermoscopic images was significantly higher than that by recognizing clinical images(P=0.010).Conclusion:The diagnostic accuracy of Youzhi AI software for skin tumors in real-world clinical settings was not as high as that of using special data sets in the laboratory.However,there was no significant difference between the diagnostic capacity of Youzhi AI software and the average diagnostic capacity of dermatologists.It can provide assistant diagnostic decisions for dermatologists in the current state.

Effects of laser irradiation on Trichophyton rubrum growth and ultrastructure

Background Trichophyton rubrum （T. rubrum） is the most common causative agent of dermatophytosis worldwide. In this study, we examined the effect of laser irradiation on the growth and morphology of T. rubrum. Methods Colonies of T. rubrum were isolated （one colony per plate）, and randomly assigned to 5 treatment groups： Q-switched 694 nm ruby laser treatment, long-pulsed Nd：YAG 1064 nm laser treatment, intense pulsed light （IPL） treatment, 308 nm excimer laser treatment and the blank control group without treatment. Standardized photographs were obtained from grown-up fungal plates prior to treatment. Colonies were then exposed to various wavelengths and fluences of laser light. To compare the growth of colonies, they were re-photographed under identical conditions three and six days post-treatment. To investigate the morphology of T. rubrum, scanning electron microscope （SEM） and transmission electron microscope （TEM） images were obtained from specimens exposed to 24 hours of laser treatment. Results Growth of T. rubrum colonies was significantly inhibited following irradiation by 694 nm Q-switched and 1064 nm long-pulsed Nd：YAG lasers. Other treatments exerted little or no effect. Q-switched laser irradiation exerted a stronger growth inhibitory effect than long-pulsed Nd：YAG laser irradiation. Following treatment by the Q-switched ruby laser system, T. rubrum hyphae became shrunken and deflated, and SEM images revealed rough, fractured hyphal surfaces, punctured with small destructive holes. TEM images showed that the hyphae were degenerating, as evidenced by the irregular shape of hyphae, rough and loose cell wall, and obscure cytoplasmic texture. Initially high electron density structure was visible in the cell; later, low-density structure appeared as a result of cytoplasmic dissolution. In contrast, the blank control group showed no obvious changes in morphology.

Whether Fire-Needle Therapy Bene?ts Plaque Psoriasis:A Multicenter,Randomized,and Controlled Trial

Objective: To observe the clinical effectiveness and safety of fire-needle therapy,an external approach of Chinese medicine in treating plaque psoriasis.Methods: This study was a two-parallel-arm randomized controlled trial.A total of 151 participants with plaque psoriasis were randomly assigned to the ?re-needle therapy group(treatment group,76 cases) or the control group(75 cases) at a 1:1 allocation ratio using SAS software.All participants received Oral Huoxue Jiedu Decoction(活血解毒汤,HXJDD) and applied externally vaseline cream twice a day.Participants in the treatment group received ?re-needle therapy once weekly for 4 weeks plus HXJDD and vaseline cream applied the same as the control group.The primary outcome measure was Psoriasis Area and Severity Index(PASI) score,and the secondary outcomes were Dermatology Life Quality Index(DLQL),and Hamilton Anxiety Rating Scale(HAMA),as well as Chinese medicine(CM) syndrome score and photos of target lesions.The indices were evaluated before and after treatment.Results: Sixty-eight patients in each group completed the study.The treatment group has not yet achieved signi?cant improvement in PASI score(P>0.05)compared to the control group.However,signi?cant differences were found between the two groups in relieving CM syndrome(P<0.05) and improving quality of life(P<0.05).Conclusions: Fire-needle appears to be safe and may have bene?t for psoriasis,the short-term treatment and small sample size limit the conclusions of this study.Further rigorous randomized controlled trials with longer treatment are recommended.

Association of HLA-DR3 and HLA-DR15 Polymorphisms wi Risk of Systemic Lupus Erythematosus

Background:Systemic lupus erythematosus (SLE)is an autoimmune disease under genetic control.Growing evidences support the genetic predisposition ofHLA-DRB1 gene polymorphisms to SLE,yet the results are not often reproducible.The purpose of this study was to assess the association of two polymorphisms ofHLA-DRB1 gene (HLA-DR3and HLA-DR15)with the risk of SLE via a comprehensive meta-analysis. Methods:This study complied with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.Case-control studies on HLA-DRB1 and SLE were searched from PubMed,Elsevier Science,Springer Link,Medline,and Cochrane Library database as of June 2018.Analysis was based on the random-effects model using STATA software version 14.0. Results:A total of 23studies were retained for analysis,including 5261cases and 9838controls.Overall analysis revealed that HLA-DR3 and HLA-DR15 polymorphisms were associated with the significant risk of SLE (odds ratio [OR]:1.60,95%confidence interval (CI):1.316-1.934,P =0.129and OR:1.68,95%CI:1.334-2.112,P =0.001,respectively).Subgroup analyses demonstrated that for both HLA-DR3and HLA-DR15polymorphisms,ethnicity was a possible source of heterogeneity.Specifically,HLA-DR3polymorphism was not associated with SLE in White populations (OR:1.60,95%CI:1.320-1.960,P =0.522)and HLA-DR15polymorphism in East Asian populations (OR:1.65,95%CI:1.248-2.173,P =0.001).In addition,source of control was another possible source for both HLA-DR3and HLA-DR15polymorphisms,with observable significance for HLA-DR3in only population-based studies (OR:1.65,95% CI:1.370-1.990,P =0.244)and for HLA-DR15in both population-based and hospital-based studies (OR:1.38,95%CI:1.078-1.760, P =0.123and OR:2.08,95%CI:1.738-2.490,P =0.881,respectively). Conclusions:HLA-DRB1 gene may be a SLE-susceptibility gene,and it shows evident ethnic heterogeneity.Further prospective validations across multiple ethnical groups are warranted.