Non-syndromic cleft lip with palate (NSCLP) is the most serious sub-phenotype of non-syndromic orofacial clefts (NSOFC), which are the most common craniofacial birth defects in humans. Here we conduct a GWAS of NSCLP with multiple independent replications, totalling 7,404 NSOFC cases and 16,059 controls from several ethnicities, to identify new NSCLP risk loci, and explore the genetic heterogeneity between sub-phenotypes of NSOFC. We identify 41 SNPs within 26 loci that achieve genome-wide significance, 14 of which are novel (RAD54B, TMEM19, KRT18, WNT9B, GSC/DICER1, PTCH1, RPS26, OFCC1/TFAP2A, TAF1B, FGF10, MSX1, LINC00640, FGFR1 and SPRY1). These 26 loci collectively account for 10.94% of the heritability for NSCLP in Chinese population. We find evidence of genetic heterogeneity between the sub-phenotypes of NSOFC and among different populations. This study substantially increases the number of genetic susceptibility loci for NSCLP and provides important insights into the genetic aetiology of this common craniofacial malformation.

Aims and Objectives: To determine the health‐related quality of life (HRQoL) of COVID‐19 patients after discharge and its predicting factors.Background: COVID‐19 has caused a worldwide pandemic and led a huge impact on the health of human and daily life. It has been demonstrated that physical and psychological conditions of hospitalised COVID‐19 patients are impaired, but the studies focus on physical and psychological conditions of COVID‐19 patients after discharge from hospital are rare.Design: A multicentre follow‐up study.Methods: This was a multicentre follow‐up study of COVID‐19 patients who had discharged from six designated hospitals. Physical symptoms and HRQoL were surveyed at first follow‐up (the third month after discharge). The latest multiple laboratory findings were collected through medical examination records. This study was performed and reported in accordance with STROBE checklist.Results: Three hundred eleven patients (57.6%) were reported with one or more physical symptoms. The scores of HRQoL of COVID‐19 patients at third month after discharge, except for the dimension of general health, were significantly lower than Chinese population norm (p < .001). Results of logistic regression showed that female (odds ratio (OR): 1.79, 95% confidence interval (CI): 1.04–3.06), older age (≥60 years) (OR: 2.44, 95% CI: 1.33–4.47) and the physical symptom after discharge (OR: 40.15, 95% CI: 9.68–166.49) were risk factors for poor physical component summary; the physical symptom after discharge (OR: 6.68, 95% CI: 4.21–10.59) was a risk factor for poor mental component summary.Conclusions: Health‐related quality of life of discharged COVID‐19 patients did not come back to normal at third month after discharge and affected by age, sex and the physical symptom after discharge.Relevance to clinical practice: Healthcare workers should pay more attention to the physical and psychological rehabilitation of discharged COVID‐19 patients. Long‐term follow‐up on COVID‐19 patients after discharge is needed to determine the long‐term impact of COVID‐19.

CaMK4 has an important function in autoimmune diseases, and the contribution of CaMK4 in psoriasis remains obscure. Here, we show that CaMK4 expression is significantly increased in psoriatic lesional skin from psoriasis patients compared to healthy human skin as well as inflamed skin from an imiquimod (IMQ)-induced mouse model of psoriasis compared to healthy mouse skin.Camk4-deficient (Camk4^−/−) mice treated with IMQ exhibit reduced severity of psoriasis compared to wild-type (WT) mice. There are more macrophages and fewer IL-17A⁺γδ TCR⁺cells in the skin of IMQ-treatedCamk4^−/−mice compared to IMQ-treated WT mice. CaMK4 inhibits IL-10 production by macrophages, thus allowing excessive psoriatic inflammation. Deletion ofCamk4in macrophages alleviates IMQ-induced psoriatic inflammation in mice. In keratinocytes, CaMK4 inhibits apoptosis as well as promotes cell proliferation and the expression of pro-inflammatory genes such asS100A8andCAMP. Taken together, these data indicate that CaMK4 regulates IMQ-induced psoriasis by sustaining inflammation and provides a potential target for psoriasis treatment.

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease affecting predominantly females. To discover additional genetic risk variants for SLE on the X chromosome, we performed a follow-up study of our previously published genome-wide association study (GWAS) data set in this study. Twelve single nucleotide polymorphisms (SNPs) within novel or unpublished loci with P-value < 1.00 × 10−02 were selected for genotype with a total of 2,442 cases and 2,798 controls(including 1,156 cases and 2,330 controls from central China, 1,012 cases and 335 controls from southern China and 274 cases and 133 controls from northern China) using Sequenom Massarry system. Associaton analyses were performed using logistic regression with sample region as a covariate through PLINK 1.07 software. Combined analysis in discovery and central validation dataset discovered a novel locus rs5914778 within LINC01420 associated with SLE at genome-wide significance (P = 1.00 × 10−08; odds ratio (OR) = 1.32). We also confirmed rs5914778 in the southern Chinese sample cohort (P = 5.31 × 10−05; OR = 1.51), and meta-analysis of the samples from the discovery, central and southern validations regions provided robust evidence for the association of rs5914778 (P = 5.26 × 10−12; OR = 1.35). However, this SNP did not show association with SLE in the northern sample (P = 0.33). Further analysis represent the association of northern was significantly heterogeneous compared to central and southern respectively. Our study increases the number of established susceptibility loci for SLE in Han Chinese population and has further demonstrated the important role of X-linked genetic risk variants in the pathogenesis of SLE in Chinese Han population.