SIRT7 activates quiescent hair follicle stem cells to ensure hair growth in mice.

Hair follicle stem cells (HFSCs) are maintained in a quiescent state until activated to grow, but the mechanisms that reactivate the quiescent HFSC reservoir are unclear. Here, we find that loss of Sirt7 in mice impedes hair follicle life-cycle transition from telogen to anagen phase, resulting in delay of hair growth. Conversely, Sirt7 overexpression during telogen phase facilitated HSFC anagen entry and accelerated hair growth. Mechanistically, Sirt7 is upregulated in HFSCs during the telogen-to-anagen transition, and HFSC-specific Sirt7 knockout mice (Sirt7f/f ;K15-Cre) exhibit a similar hair growth delay. At the molecular level, Sirt7 interacts with and deacetylates the transcriptional regulator Nfatc1 at K612, causing PA28γ-dependent proteasomal degradation to terminate Nfatc1-mediated telogen quiescence and boost anagen entry. Cyclosporin A, a potent calcineurin inhibitor, suppresses nuclear retention of Nfatc1, abrogates hair follicle cycle delay, and promotes hair growth in Sirt7-/- mice. Furthermore, Sirt7 is downregulated in aged HFSCs, and exogenous Sirt7 overexpression promotes hair growth in aged animals. These data reveal that Sirt7 activates HFSCs by destabilizing Nfatc1 to ensure hair follicle cycle initiation.

Integrated bioinformatics analysis and experimental validation identifies CPE as a potential biomarker and therapeutic target for skin aging.

Ageing is an inevitable biological process characterized by progressive decline in physiological functions. It is a complex natural phenomenon that will cause structural and functional decline. Despite substantial progress in understanding the mechanism of ageing, both predictive biomarkers and preventive therapies remain limited. Using Weighted Gene Co-expression Network Analysis (WGCNA) and machine learning techniques, we identified Carboxypeptidase E (CPE) as a pivotal marker of skin ageing, based on ageing-related bulk transcriptome and single-cell transcriptome data. Next, our investigation reveals downregulation of CPE in replicative, UVA-induced, and H2O2-induced senescent human dermal fibroblast cells (HDFs). Furthermore, shRNA-mediated CPE knockdown induced HDFs senescence, and overexpression of CPE delayed HDFs senescence. Moreover, downregulated CPE inhibits collagen synthesis and induces inflammation, highlighting its potential as a therapeutic target for skin ageing. In conclusion, our study demonstrated that CPE functions as a predictor and optional target for therapeutic intervention of skin ageing.

Expert consensus on perioperative integrated skincare for noninvasive energy-based device aesthetic procedures in clinical practice in China.

BACKGROUND: Noninvasive energy-based device (NI-EBD) aesthetic procedures has recently gained widespread usage for treating various skin conditions, enhancing skin texture and performing rejuvenation-related procedures. However, practically all NI-EBD procedures result in variable degrees of damage to the skin barrier, inducing pathological and physiological processes such as oxidative stress and inflammation, and only a small percentage of individuals possess the innate ability to restore it. OBJECTIVE: To introduce the concept of integrated skincare and establish standardized operational procedures for perioperative integrated skincare, and furnish a theoretical basis for clinical diagnosis and treatment performed by professional medical aestheticians. METHODS: The author leveraged domestic and international guidelines, clinical practice expertise and evidence-based research, adapting them to suit the specific circumstances in China. RESULTS: The consensus were provided four parts, including concept and essence of integrated skincare, integrated skincare significance during the perioperative phase of NI-EBD procedures, active ingredients and functions of effective skincare products, standardized perioperative skincare procedure for NI-EBD procedures and precautions. For the standardized perioperative skincare procedure, four recommendations were listed according to different stages during NI-EBD procedures. CONCLUSION: These recommendations create the 'Expert Consensus on Perioperative Integrated Skincare for Noninvasive Energy-Based Device Aesthetic Procedures in Clinical Practice in China'.

Paroxetine is an effective treatment for refractory erythema of rosacea: Primary results from the Prospective Rosacea Refractory Erythema Randomized Clinical Trial.

BACKGROUND: Patients with refractory erythema of rosacea have limited treatment options. OBJECTIVE: To evaluate the efficacy and safety of a 12-week course of paroxetine for moderate-to-severe erythema of rosacea. METHODS: In a multicenter, randomized, double-blinded, placebo-controlled trial, patients with refractory erythema of rosacea were randomly assigned (1:1) to receive paroxetine 25 mg daily or placebo for 12 weeks. RESULTS: Overall, 97 patients completed the study (paroxetine: 49; placebo: 48). The primary end point was the proportion of participants achieving Clinical Erythema Assessment success (defined as Clinical Erythema Assessment score of 0, 1, or ≥2-grade improvement from baseline) at week 12; this was significantly greater in the paroxetine group than in the placebo group (42.9% vs 20.8%, P = .02). Some secondary end points were met, such as flushing success with point reductions ≥2 (44.9% vs 25.0%, P = .04) and improvement in overall flushing (2.49 ± 3.03 vs 1.68 ± 2.27, P = .047), burning sensation (46.9% vs 18.8%, P = .003), and depression (P = .041). The most reported adverse events associated with paroxetine were dizziness, lethargy, nausea, dyspepsia, and muscle tremors. LIMITATIONS: Only a single-dosage regimen of paroxetine within a 12-week study was evaluated. CONCLUSIONS: Paroxetine is an effective and well-tolerated alternative treatment for moderate-to-severe erythema of rosacea.

GBP5 exacerbates rosacea-like skin inflammation by skewing macrophage polarization towards M1 phenotype through the NF-κB signalling pathway.

BACKGROUND: Rosacea is a chronic inflammatory skin disease with increased macrophage infiltration. However, the molecular mechanism remains unclear. OBJECTIVES: To determine the significance of macrophage infiltration, and the correlation between Guanylate-binding protein 5 (GBP5) and polarization of macrophages in rosacea-like inflammation. METHODS: Here we tested the hypothesis that Guanylate-binding protein 5 (GBP5) aggravates rosacea-like skin inflammation by promoting the polarization of the M1 macrophages through the NF-κB signalling pathway. We depleted macrophage by injecting clodronate-containing liposomes. We next explored the association between GBP5 and macrophage in rosacea tissue through transcriptome analysis and immunofluorescence analysis. We evaluated the severity of rosacea-like skin inflammation when BALB/c mice were injected with GBP5 siRNA intradermally daily for three consecutive days. At last, to study the causality of knocking down GBP5-blunted M1 macrophage polarization, THP-1 cell was treated with GBP5 siRNA. RESULTS: Macrophage depletion ameliorated rosacea-like skin inflammation in mice, implying the important role of macrophages in rosacea. Based on the transcriptome analysis, Guanylate-binding protein 5 (GBP5) was identified as hub gene that was associated with macrophage infiltration in rosacea. Next, we found that GBP5 expression was significantly upregulated in rosacea tissues and positively correlated with macrophage infiltration, the immunofluorescence analysis revealed the co-localization between GBP5 and macrophages. In vivo, silencing of GBP5 attenuated rosacea-like skin inflammation in the LL-37-induced mouse model and suppressed the expression of M1 signature genes such as IL-6, iNOS and TNF-a. In vitro, knocking down GBP5 significantly blunted the polarization of the M1 macrophages partly by repressing the activation of the NF-κB signalling pathways. CONCLUSIONS: Together, our study revealed the important role of macrophages in rosacea and identified GBP5 as a key regulator of rosacea by inducing M1 macrophage polarization via NF-κB signalling pathways.

A case of pseudomyogenic hemangioendothelioma misdiagnosed as low-grade malignant fibrous histiocytoma and review of literature. / è¯¯è¯Šä¸ºä½Žåº¦æ¶æ€§çº¤ç»´ç»„ç»‡ç»†èƒžç˜¤çš„å‡è‚Œæºæ€§è¡€ç®¡å† çš®ç˜¤1ä¾‹å¹¶æ–‡çŒ®å¤ä¹ .

Pseudomyogenic hemangioendothelioma (PHE) is a rare angiogenic tumor. Histologically, the morphological characteristics of neoplastic vessels and endothelial differentiation are not obvious, and it is easy to be confused with epithelioid sarcoma, epithelioid hemangioendothelioma and myogenic tumor. PHE usually occurs in arms and legs in young people and has a significant male predominance. The tumor has a predilection for the distal extremities and its typical manifestation is multiple center invasion of a single limb, which can involve all layers of skin and subcutaneous tissues,and is often accompanied by abvious pain. Histologically, PHE is characterized by infiltrative growth of tumor. Most tumor lesions are composed of sheets and loose fascicles of plump spindle or epithelioid cells within a background of variably prominent inflammatory infiltration, which was commonly composed of neutrophils. Some cells may resemble rhabdomyoblasts, and nuclear atypia and mitosis were rare. The tumor cells generally expressed positive cytokeratin (CK), ETS-related gene (ERG), Friend leukemia virus integration 1 (FLI1) and integrase interactor 1(INI1). In some cases, the tumor cells expressed CD31. A case of a young woman was reported in this paper, who presented with a subcutaneous mass with severe pain and was chronologically misdiagnosed with herpes zoster, low-grade malignant fibrous histiocytoma and epithelioid hemangioendothelioma. In this study, the clinical and pathological features, differential diagnosis and the latest progress in therapy of PHE were analyzed based on relevant literature.

Exploring metformin as a candidate drug for rosacea through network pharmacology and experimental validation.

Rosacea is a common chronic inflammatory disease that affects the middle of the face. Due to the unclear pathogenesis, the effective treatment options for rosacea remain limited. In this study, weighted gene co-expression network analyses (WGCNA) identified three rosacea-related hub modules, which were involved in immune-, metabolic- and development- related signaling pathways. Next, the key genes from green and brown modules were submitted to CMap database for drug prediction and metformin was identified as a candidate drug for rosacea. Moreover, network pharmacology analysis identified pharmacological targets of metformin and demonstrated that metformin could help in treating rosacea partly by modulating inflammatory and angiogenesis signaling pathways. Finally, we verified the therapeutic role and mechanism of metformin on rosacea in vivo and vitro. We found that metformin treatment significantly improved rosacea-like skin lesions including immune cells infiltration, cytokines/chemokines expression and angiogenesis. Moreover, metformin suppressed LL37- and TNF-α-induced the ROS production and MAPK-NF-κB signal activation in keratinocytes cells. In conclusion, our findings identified and verified metformin as a novel therapeutic candidate for rosacea, and it alleviates the pathological symptoms, possibly by suppressing inflammatory responses, angiogenesis in rosacea.

Relationship Between Tea Drinking Behaviour and Rosacea: A Clinical Case-control Study.

The exact mechanisms of rosacea development are unknown, but it has been suggested that tea consumption may be associated with its development. To determine the relationship between tea drinking behaviour and rosacea, this clinical case-control study recruited 2,063 participants, who completed a questionnaire about tea drinking behaviour. A 1:1 ratio propensity score matching method was used to generate 619 cases and 619 controls. High-frequency tea drinking (3 times/day: adjusted odds ratio (aOR) 2.592; 95% confidence interval (95% CI) 1.225-5.485; ≥ 4 times/day; aOR 8.86; 95% CI 3.43-22.887), non-fermented tea (aOR 2.172; 95% CI 1.562-3.022), and hot tea (aOR 2.793; 95% CI 1.796-1.344) were associated with an increased risk of rosacea. Further results showed that these tea drinking behaviours were significantly associated with an increased risk of flushing (aOR 1.41; 95% CI 1.07-1.87) and erythema (aOR 1.48; 95% CI 1.10-2.00). Tea drinking behaviour is closely related to rosacea and.

Efficacy of non-ablative fractional 1440-nm laser therapy for treatment of facial acne scars in patients with rosacea: a prospective, interventional study.

Acne scarring is one of the most common facial skin disorders. The appropriate treatments for acne scars in patients with rosacea have not been studied. This study was designed to evaluate the efficacy and safety of non-ablative fractional 1440-nm laser (1440-nm NAFL) therapy for treatment of atrophic acne scars in patients with rosacea. In this prospective, interventional study, 32 patients with rosacea and acne scars underwent three sessions of 1440-nm NAFL therapy. Therapy efficacy, epidermal barrier function, and side effects were evaluated. Thirty patients completed and the median acne scar scores significantly reduced from 45 (30, 50) to 15 (15, 30) after three treatments (P < 0.001). The improvement score of acne scars was 2.7 ± 0.7; 22 (73.3%) were satisfied or highly satisfied. The rosacea erythema scores changed from 2.1 ± 0.4 to 1.9 ± 0.5 (P = 0.326), and flushing, burning, and stinging were not worse. The oil content after treatments was significantly reduced (P < 0.001), while there was no significant difference in other indicators of skin barrier function. The quality-of-life score decreased from 17.5 ± 3.8 to 14.1 ± 3.0 (P < 0.001). No serious side effects were observed. The 1440-nm NAFL therapy is effective in the treatment of acne scaring in patients with rosacea with little damage to the skin barrier.

Relationship between the exercise and severity of androgenic alopecia. / è¿åŠ¨ä¸Žé›„æ¿€ç´ æ€§ç§ƒå‘ç— æƒ å˜åŒ–çš„å ³ç³».

OBJECTIVES: Androgenic alopecia (AGA) is the most common type of alopecia. At present, the study on AGA mostly focuses on drugs, laser technology and hair transplantation, while the lifestyle factor that may delay the course of AGA and improve the condition of AGA is neglected. This study aims to investigate the relationship between the exercise and severity of androgenic alopecia, and to help AGA patients to choose suitable forms and amounts of exercise. METHODS: Patients, who were diagnosed with AGA from May 13, 2020 to August 25, 2020, were the subjects of the survey. Through the internet online questionnaire survey, the information regarding demographics, exercise forms (lifestyle exercises, stretching exercises, aerobic exercises, and anaerobic exercises), exercise frequency (0-2 times/week, 3-4 times/week, and 5-7 times/week), exercise duration (<30, 30-60, and >60 min/time), and family history (androgenic alopecia, alopecia areata, and scarring alopecia) was obtained. Combination of patient self-assessment and doctor's photo examination was used to evaluate the changes (improvement, aggravation, and natural course) of the condition after 6 months of exercise. Single factor analysis and logistic regression analysis were used to study the factors related to the changes before and after exercise. RESULTS: A total of 592 AGA patients were recruited. Among them, 215 were male patients (36.32%), and 377 were female patients (63.68%); 91 patients (15.37%) were improved after 6 months of exercise, 448 patients (75.68%) were in natural progress, and 53 patients (8.95%) were aggravated. A total of 439 AGA patients were involved in non-life sports. After 6 months of exercise, 137 patients (31.21%) with scalp itching and scaling were reduced, 65 patients (14.81%) with greasy scalp was reduced, and 204 patients (46.47%) with anxiety and depression symptoms were improved compared with the previous period, and 356 patients (81.10%) showed that their sleep quality was improved compared with before. The changes in the condition before and after exercise are related to exercise style (P<0.001), exercise frequency (P=0.033), exercise duration (P=0.044), but not related to gender (P=0.358) and family history (P=0.052). The degree of improvement in AGA patients, who performed aerobic exercise, was 5.416 times of those who only performed life-like exercises (OR=5.416, P<0.001); the degree of improvement in AGA patients with each exercise time >60 min was 3.106 times of those with each exercise time <30 min (OR=3.106, P=0009). CONCLUSIONS: Doing aerobic exercise or each exercise time >60 min helps to delay the progress of AGA and improve the symptom of AGA.

ADAMDEC1 promotes skin inflammation in rosacea via modulating the polarization of M1 macrophages.

Rosacea is a chronic inflammatory cutaneous disease which mainly affects central face, leading to cosmetic disfigurement and compromised social psychology in billions of rosacea patients. Though the exact etiology of rosacea remains elusive, accumulating evidence has highlighted the dysfunction of innate immunity and inflammation in rosacea pathogenesis. Disintegrin Metalloprotease ADAM-like Decysin-1 (ADAMDEC1) is an orphan ADAM-like metalloprotease which is believed to be closely related to inflammation. Here for the first time, we reported that Adamdec1 expression was significantly increased in the skin lesions of rosacea patients and LL37-induced rosacea-like mouse models. Immunofluorescence analysis revealed co-localization of ADAMDEC1 and macrophages in patient and mouse biopsies. In cellular experiment, the expression of ADAMDEC1 was prominently elevated in M1 but not M2 macrophages. Knocking down of ADAMDEC1 significantly blunted M1 polarization in macrophages induced from human monocytes and THP-1 cell lines. Furthermore, silencing of Adamdec1 in LL-37-induced mouse model also suppressed the expression of M1 signature genes such as IL-6, iNOS and TNF-α, resulting in attenuated rosacea-like phenotype and inflammation. Taken together, our results demonstrate that ADAMDEC1 plays a pro-inflammatory role in rosacea via modulating the M1 polarization of macrophages.

Association between rosacea and cardiometabolic disease: A systematic review and meta-analysis.

BACKGROUND: Rosacea is recognized as a chronic inflammatory cutaneous disorder associated with multiple systemic illnesses. However, the association between rosacea and cardiometabolic disease (CMD) remains controversial. OBJECTIVE: To evaluate the association between rosacea and CMD by a systematic review and meta-analysis. METHODS: A comprehensive search of studies published before October 16, 2019, was performed in databases of PubMed, Embase, Cochrane Library, and Web of Science. The pooled risk ratios or standardized mean differences were calculated. RESULTS: Thirteen studies were included, representing 50,442 patients with rosacea. Patients with rosacea had higher prevalence of dyslipidemia, higher prevalence of hypertension, higher total cholesterol, higher low-density lipoprotein, higher triglycerides, higher systolic blood pressure, higher diastolic blood pressure, and higher fasting blood glucose. Rosacea was not associated with ischemic heart disease, stroke, diabetes, and high-density lipoprotein. LIMITATIONS: No subgroup analysis could be performed according to the subtypes and severity of rosacea. CONCLUSIONS: Rosacea showed a correlation with hypertension and dyslipidemia but not with ischemic heart disease, stroke, or diabetes. We advocate screening for CMD indicators among patients with rosacea, which may be helpful for diagnosis and appropriate treatment at an early stage of disease.

Skincare Habits and Rosacea in 3,439 Chinese Adolescents: A University-based Cross-sectional Study.

The pathogenesis of rosacea remains unclear but has been reported to correlate with skin barrier function. The objective of this study was to elucidate the skincare habits of Chinese adolescents and determine the relationship between skincare habits and rosacea. A university-based cross-sectional investigation included 310 rosacea cases and 3,129 healthy controls who underwent health examinations and completed a questionnaire about daily skincare habits. Fitzpatrick skin phototype IV is a protective factor against rosacea (adjusted adds ratio (aOR) 0.40; 95% confidence interval (CI) 0.22-0.72). Long bath duration (≥ 11 min, aOR 2.60; 95% CI 1.01-6.72) and frequent use of facial cleansers (≥ 2 times/day, aOR 1.70; 95% CI 1.17-2.36) were positively associated with rosacea, but bath frequency (p = 0.22), water temperature (p = 0.53), and sun protection (p = 0.65) were not associated with rosacea. Inappropriate skincare habits, including extended bath durations and frequent use of facial cleansers, significantly increase the risk of rosacea in Chinese adolescents.

Relationship between the incidence of rosacea and drinking or smoking in China. / ä¸­å›½äººç¾¤çŽ«ç‘°ç—¤ç–®å‘ç— ä¸Žé¥®é ’ã€å¸çƒŸçš„å ³ç³».

OBJECTIVES: To explore the relationship between the incidence of rosacea and drinking, smoking, gender or age, and to provide some basis for the diagnosis, treatment and mechanism of rosacea. METHODS: A total of 1 180 patients with rosacea and 1 008 non-rosacea patients diagnosed in the Department of Dermatology of Xiangya Hospital were included in the study. Logistic analysis was performed on the incidence factors, and the differences between the two groups in different age groups were compared. RESULTS: There was no significant difference in gender between the two groups (P>0.05). Logistic analysis showed that drinking had no effect on the incidence of rosacea (P>0.05); while smoking, gender, and age had an effect on the incidence of rosacea (P<0.05). The highest proportion of patients with rosacea was 25-34 years old. CONCLUSIONS: The incidence of rosacea has nothing to do with alcohol consumption; while smoking, gender, and age affect the incidence. Smoking and women are the risk factors, and the most common age of rosacea is at 25-34 years old.

Suppressing ROS-TFE3-dependent autophagy enhances ivermectin-induced apoptosis in human melanoma cells.

Melanoma is an aggressive skin malignancy with a high mortality rate; however, successful treatment remains a clinical challenge. Ivermectin, a broad-spectrum antiparasitic drug, has recently been characterized as a potential anticancer agent due to its observed antitumor effects. However, the molecular mechanisms of ivermectin remain poorly understood. In the current study, we tested the involvement of autophagy in the ivermectin mechanism of action in human melanoma cells. We exposed SK-MEL-28 cells to different concentrations of ivermectin (2.5, 5, and 10 µM) for 24 hours. Here, ivermectin-induced apoptosis, as evidenced by the upregulation of cleaved poly (ADP-ribose) polymerase, BAX expression, and caspase-3 activity and downregulation of BCL-2 expression. In line with the apoptosis response, ivermectin triggered autophagy. Pharmacological or genetic inhibition of autophagy further sensitized SK-MEL-28 cells to ivermectin-induced apoptosis. Mechanistically, ivermectin-induced TFE3(Ser321) dephosphorylation, activated TFE3 nuclear translocation and increased TFE3 reporter activity, which contributed to lysosomal biogenesis and the expression of autophagy-related genes, and subsequently, initiated autophagy in SK-MEL-28 cells. Moreover, N-acetyl-cysteine, an reactive oxygen species (ROS) scavenger, abrogated the effects of ivermectin on TFE3-dependent autophagy. Taken together, we demonstrated that ivermectin increases TFE3-dependent autophagy through ROS signaling pathways in human melanoma cells and that inhibiting autophagy enhances ivermectin-induced apoptosis in human melanoma cells.

[Expression pattern of mTOR subunits Raptor and Rictor in mouse hair follicle cycle].

OBJECTIVE: To detemine the expression pattern of mTOR complex subunits Raptor and Rictor in the hair follicles of mice at different hair follicle stages, and to explore its significance. 
 Methods: Immunostaining of Ki-67, a proliferative marker, was used to determine the precise hair follicle stages of mouse dorsal skin at different postnatal time points. Real-time PCR was used to detect the mRNA expression of Raptor and Rictor in mouse dorsal skin at 43 days after birth (P43, early telogen), 56 days after birth (P56, mid-telogen), 69 days after birth (P69, late telogen) and 74 days after birth (P74, early anagen). The expression intensity and localization of Raptor and Rictor at different stages of hair cycle were tested by co-immumostaining.
 Results: Ki-67 immunostaining showed that the time points (P43, P56, P69, P74) and hair follicle stages (early telogen, mid-telogen, late telogen, early anagen) of the dorsal skin were consistent with each other. The results of real-time PCR and immunostaining were consistent, showing that the expression of Raptor and Rictor did not changed in the early-, mid-, late telogen, and early anagen. However, Raptor was specifically expressed in the bulge where hair follicle stem cells (HFSCs) are residing in, and Rictor was mainly detected in inner root sheath (IRS) cells. 
 Conclusion: The expression of Raptor and Rictor does not altered in the hair follicles at different hair follicle stages, but Raptor and Rictor are specifically expressed in the HFSCs and IRS cells, respectively, indicating that Raptor might be a molecular marker for HFSCs, and Rictor might be involved in the maintenance of IRS and formation of hair shaft.

[Psychosocial factors of chronic hand eczema].

OBJECTIVE: To study the psychosocial factors in patient with chronic hand eczema (CHE).
 Methods: Personality traits, emotional state, and quality of life of 240 patients with CHE and 221 normal control (NC) subjects were assessed by General Questionnaire, Eysenck Personality Questionnaire (EPQ), Self-Rating Depression Scale (SDS), Self-Rating Anxiety (SAS), and Eczema Quality of Life Scale (EQOLS).
 Results: In comparison, EPQ scores, scores of extraversion (E) factor in patients with CHE were significantly lower than those in NC subjects (P<0.01), but scores of neuroticism (N) factor in patients with CHE were significantly higher than those in NC subjects (P<0.01), while there was no significant difference in scores of psychoticism (P) and lie (L) factors between two groups (P>0.05). Patients with CHE had significantly higher scores in SDS and SAS compared with the NC subjects (P<0.01). Patients with CHE had significantly higher scores in scale of morbid, physical, social, psychological, general quality of life, and total scores of EQOLS compared with the NC subjects (P<0.01). The level of skin lesions and the degree of itch were significantly correlated with scores in scale SDS, SAS, morbid, physical, social, psychological, general quality of life, and total scores of EQOLS compared with the NC subjects (P<0.05).
 Conclusion: Personality of patients with CHE is prone to emotional instability of introverts.Patients with CHE have a higher level of depression and anxiety, and exert a negative effect on their quality of life, which is related to severity of disease.

Meta-analysis followed by replication identifies loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with systemic lupus erythematosus in Asians.

Systemic lupus erythematosus (SLE) is a prototype autoimmune disease with a strong genetic involvement and ethnic differences. Susceptibility genes identified so far only explain a small portion of the genetic heritability of SLE, suggesting that many more loci are yet to be uncovered for this disease. In this study, we performed a meta-analysis of genome-wide association studies on SLE in Chinese Han populations and followed up the findings by replication in four additional Asian cohorts with a total of 5,365 cases and 10,054 corresponding controls. We identified genetic variants in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with the disease. These findings point to potential roles of cell-cycle regulation, autophagy, and DNA demethylation in SLE pathogenesis. For the region involving TET3 and that involving CDKN1B, multiple independent SNPs were identified, highlighting a phenomenon that might partially explain the missing heritability of complex diseases.