BACKGROUND The narrow host range of Mycobacterium leprae and the fact that it is refractory to growth in culture has limited research on and the biologic understanding of leprosy. Host genetic factors are thought to influence susceptibility to infection as well as disease progression. METHODS We performed a two-stage genomewide association study by genotyping 706 patients and 1225 controls using the Human610-Quad BeadChip (Illumina). We then tested three independent replication sets for an association between the presence of leprosy and 93 single-nucleotide polymorphisms (SNPs) that were most strongly associated with the disease in the genomewide association study. Together, these replication sets comprised 3254 patients and 5955 controls. We also carried out tests of heterogeneity of the associations (or lack thereof) between these 93 SNPs and disease, stratified according to clinical subtype (multibacillary vs. paucibacillary). RESULTS We observed a significant association (P<1.00×10 −10) between SNPs in the genes CCDC122, C13orf31, NOD2, TNFSF15, HLA-DR, and RIPK2 and a trend toward an association (P = 5.10×10 −5) with a SNP in LRRK2. The associations between the SNPs in C13orf31, LRRK2, NOD2, and RIPK2 and multibacillary leprosy were stronger than the associations between these SNPs and paucibacillary leprosy. CONCLUSIONS Variants of genes in the NOD2-mediated signaling pathway (which regulates the innate immune response) are associated with susceptibility to infection with M. leprae.

HLA-B*13:01 was associated with the development of the dapsone hypersensitivity syndrome among patients with leprosy. (Funded by the National Natural Science Foundation of China and others.).

We performed a genome-wide association study with 706 individuals with leprosy and 5,581 control individuals and replicated the top 24 SNPs in three independent replication samples, including a total of 3,301 individuals with leprosy and 5,299 control individuals from China. Two loci not previously associated with the disease were identified with genome-wide significance: rs2275606 (combined P = 3.94 × 10(-14), OR = 1.30) on 6q24.3 and rs3762318 (combined P = 3.27 × 10(-11), OR = 0.69) on 1p31.3. These associations implicate IL23R and RAB32 as new susceptibility genes for leprosy. Furthermore, we identified evidence of interaction between the NOD2 and RIPK2 loci, which is consistent with the biological association of the proteins encoded by these genes (NOD2-RIPK2 complex) in activating the NF-κB pathway as a part of the host defense response to infection. Our findings have expanded the biological functions of IL23R by uncovering its involvement in infectious disease susceptibility and suggest a potential involvement of autophagocytosis in leprosy pathogenesis. The IL23R association supports previous observations of the marked overlap of susceptibility genes for leprosy and Crohn's disease, implying common pathogenesis mechanisms.

Originally identified as a B-cell marker, expression of the cell surface molecule CD24 has meanwhile been observed in a variety of human malignancies. It appears to function as a ligand of P-Selectin, an adhesion molecule that is present in activated platelets and endothelial cells. We aimed to determine the rate of CD24 expression in our nonsmall cell lung cancer (NSCLC) collection and to clarify its correlation with clinicopathological parameters including patients' survival. A total of 89 NSCLC were analysed immunohistochemically using a monoclonal CD24 antibody (clone 24C02) and a standard detection system (LSAB, DAKO) on NSCLC tissue microarrays (TMA). The staining was semiquantitatively scored (0, 1+, 2+, 3+) and grouped into high (2+, 3+)-and low (0, 1+)-level expression for statistical analysis. A high level of CD24 expression was observed in 45% of the cases, preferentially adenocarcinomas. Patients whose tumours had a high CD24 expression showed a significantly shorter median survival time of 23 months vs 38 months (P ¼ 0.033, log-rank test). Similarly tumour, grading, nodal status and clinical stage were significant prognostic markers in univariate survival analysis. Importantly, in the Cox regression-based multivariate analysis, CD24 expression (P ¼ 0.025) together with tumour stage (P ¼ 0.006) and grade (P ¼ 0.011) proved to be independent prognostic parameters. We hypothesise that the decreased survival of NSCLC patients with strongly CD24-positive tumours is related to an enhanced propensity of haematogenous metastasis formation, which might be P-Selectin mediated.

Genome-wide association studies (GWAS) have led to the discovery of several susceptibility loci for leprosy with robust evidence, providing biological insight into the role of host genetic factors in mycobacterial infection. However, the identified loci only partially explain disease heritability, and additional genetic risk factors remain to be discovered. We performed a 3-stage GWAS of leprosy in the Chinese population using 8,313 cases and 16,017 controls. Besides confirming all previously published loci, we discovered six new susceptibility loci, and further gene prioritization analysis of these loci implicated BATF3, CCDC88B and CIITA-SOCS1 as new susceptibility genes for leprosy. A systematic evaluation of pleiotropic effects demonstrated a high tendency for leprosy susceptibility loci to show association with autoimmunity and inflammatory diseases. Further analysis suggests that molecular sensing of infection might have a similar pathogenic role across these diseases, whereas immune responses have discordant roles in infectious and inflammatory diseases.

SUMMARY Controversy exists on the advantages of robotic McKeown esophagectomy (RME) versus thoraco-laparoscopic McKeown esophagectomy (TLME). The aim was to evaluate the short- and mid-term outcomes of RME and TLME in the treatment of patients with esophageal squamous cell carcinoma (ESCC). A consecutive series of 652 patients, 280 in RME and 372 in TLME, who underwent minimally invasive McKeown esophagectomy for ESCC at our department from November 2015 to June 2018 was analyzed. A propensity score-matched comparison with clinicopathological covariates was performed between the two groups. Complications were categorized based on the Esophagectomy Complications Consensus Group (ECCG) recommendation. To identify the recurrence, all patients with R0 resection were followed with a median follow-up period of 20.2 months (range 1–33 months). After propensity score matching, 271 patients were identified for each cohort. In the matched cohorts, two patients died within 90 days in TLME, whereas no patients died in RME. RME was associated with similar intraoperative blood loss (P = 0.895), but with shorter surgical duration (244.5 vs. 276.0 min, P &lt; 0.001), shorter thoracic duration (85.0 vs. 102.9 min, P &lt; 0.001) and lower thoracic conversions (0.7% vs. 5.9%, P = 0.001). In spite of the similar results on total and thoracic lymph nodes dissection, RME yielded more lymph nodes along recurrent laryngeal nerve (4.8 vs. 4.1, P = 0.012), as well as the higher incidence of recurrent nerve injury (29.2% vs. 15.1%, P &lt; 0.001) when compared to TLME. Tumor recurrence occurred in 30 patients and was locoregional only in 9 (3.5%) patients, systemic only in 17 (6.7%) patients, and combined in 4 (1.6%) patients in RME, while in 26 patients and was locoregional only in 10 (10.6%) patients, systemic only in 7 (2.8%) patients, and combined in 9 (3.6%) patients in TLME. RME was associated with a lower rate of mediastinal lymph nodes recurrence (2.0% vs. 5.3%, P = 0.044). Overall and disease-free survival was not different between the two cohorts (P = 0.097 and P = 0.248, respectively). RME was shown to be a safe and oncologically effective approach with favorable short- and mid-term outcomes in the treatment of patients with ESCC.

Suboptimal health status (SHS) has become a new public health challenge in urban China. Despite indications that SHS may be associated with progression or development of chronic diseases such as cardiovascular and metabolic diseases, there are few reports on SHS investigations. To explore the relationship between SHS and traditional cardiovascular risk factors, a cross-sectional study was conducted in a sample of 4,881 workers employed in 21 companies in urban Beijing. Blood pressure, glucose, lipid levels (total cholesterol, high-density lipoprotein [HDL] cholesterol, lowdensity lipoprotein [LDL] cholesterol and triglycerides), cortisol, and body mass index were measured. SHS score was derived from data collection in the SHS questionnaire (SHSQ-25). Univariate analysis and linear two-level model were used to analyze the association of SHS with the cardiovascular risk factors. Serum cortisol level was much higher among the SHS high-score group than that among the low SHS score group (204.31 versus 161.33 ng/ml, PG0.001). In a linear two-level model, we found correlation between SHS and systolic blood pressure, diastolic blood pressure, plasma glucose, total cholesterol, and HDL cholesterol among men, and correlation between SHS and systolic blood pressure, diastolic blood pressure, total cholesterol, triglyceride, and HDL cholesterol among women after controlling for age, education background, occupation, smoking, and physical activity. SHS is associated with cardiovascular risk factors and contributes to the development of cardiovascular disease. SHS should be recognized in the health care system, especially in primary care.

Leprosy, a chronic infectious disease, results from the uncultivable pathogen Mycobacterium leprae (M. leprae), and usually progresses to peripheral neuropathy and permanent progressive deformity if not treated. Previously published genetic studies have identified 18 gene/loci significantly associated with leprosy at the genome-wide significant level. However as a complex disease, only a small proportion of leprosy risk could be explained by those gene/loci. To further identify more susceptibility gene/loci, we hereby performed a three-stage GWAS comprising 8,156 leprosy patients and 15,610 controls of Chinese ancestry. Four novel loci were identified including rs6807915 on 3p25.2 (P=1.94 × 10−8, OR=0.89), rs4720118 on 7p14.3 (P=3.85 × 10−10, OR=1.16), rs55894533 on 8p23.1 (P=5.07 × 10−11, OR=1.15) and rs10100465 on 8q24.11 (P=2.85 × 10−11, OR=0.85). Altogether, these findings have provided new insight and significantly expanded our understanding of the genetic basis of leprosy.