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.).

; and the Dapsone Hypersensitivity Syndrome Prevention Working Group IMPORTANCE Dapsone hypersensitivity syndrome (DHS) is the most serious adverse reaction associated with dapsone administration and one of the major causes of death in patients with leprosy, whose standard treatment includes multidrug therapy (MDT) with dapsone, rifampicin, and clofazimine. Although the HLA-B*13:01 polymorphism has been identified as the genetic determinant of DHS in the Chinese population, no studies to date have been done to evaluate whether prospective HLA-B*13:01 screening could prevent DHS by identifying patients who should not receive dapsone. OBJECTIVE To evaluate the clinical use of prospective HLA-B*13:01 screening for reduction of the incidence of DHS by excluding dapsone from the treatment for patients with HLA-B*13:01-positive leprosy. DESIGN, SETTING, AND PARTICIPANTS A prospective cohort study was conducted from February 15, 2015, to April 30, 2018, in 21 provinces throughout China. A total of 1539 patients with newly diagnosed leprosy were enrolled who had not received dapsone previously. After excluding patients who had a history of allergy to sulfones or glucose-6-phosphate dehydrogenase deficiency, 1512 individuals underwent HLA-B*13:01 genotyping. All of the patients were followed up weekly for the first 8 weeks after treatment to monitor for adverse events. EXPOSURES Patients who were HLA-B*13:01 carriers were instructed to eliminate dapsone from their treatment regimens, and noncarrier patients received standard MDT. MAIN OUTCOMES AND MEASURES The primary outcome was the incidence of DHS. The historical incidence rate of DHS (1.0%) was used as a control. RESULTS Among 1512 patients (1026 [67.9%] men, 486 [32.1%] women; mean [SD] age, 43.1 [16.2] years), 261 (17.3%) were identified as carriers of the HLA-B*13:01 allele. A total of 714 adverse events in 384 patients were observed during the follow-up period. Dapsone hypersensitivity syndrome did not develop in any of the 1251 patients who were HLA-B*13:01-negative who received dapsone, while approximately 13 patients would be expected to experience DHS, based on the historical incidence rate of 1.0% per year (P = 2.05 × 10 −5). No significant correlation was found between other adverse events, including dermatologic or other events, and HLA-B*13:01 status. CONCLUSIONS AND RELEVANCE Prospective HLA-B*13:01 screening and subsequent elimination of dapsone from MDT for patients with HLA-B*13:01-positive leprosy may significantly reduce the incidence of DHS in the Chinese population.

This study aimed to evaluate the impact of a short insemination procedure on embryo development, assess the reliability of a fertilization check prior to the appearance of pronuclei and elucidate the role of rescue intracytoplasmic sperm injection (R-ICSI). Patients who had ≥9 eggs, were aged <38 years and had normal semen samples were included. The sibling eggs of each patient were divided into two groups; one half for conventional fertilization (IVF; insemination time, 20 h) and the other half for short insemination (insemination time, 5 h). R-ICSI was performed where total fertilization failure (TFF) was deemed to have occurred in the short insemination group. In total, 2,465 eggs were included. No significant differences were found in fertilization, abnormal fertilization, embryo quality, clinical pregnancy and implantation rates between the short insemination and conventional insemination groups. In the short insemination group, R-ICSI was performed in 11 cycles (6.7%); in 6 of these cycles, fertilization occurred in the patient's eggs in the 20 h insemination group, while in the other 5 cycles, the patient's eggs were not fertilized after 20 h insemination either. Following R-ICSI, 19 of 36 eggs were normally fertilized. Subsequently, 7 embryos were transferred in 4 fresh cycles resulting in one ectopic pregnancy. In conclusion, the short insemination procedure does not improve embryo development and pregnancy rates. Short insemination combined with early R-ICSI may be a method of preventing total fertilization failure, albeit with poor accuracy.

Leprosy continues to be detected at near stable rates in China even with established control programs, necessitating new knowledge and alternative methods to interrupt transmission. A molecular epidemiology investigation of 190 patients was undertaken to define M. leprae strain types and discern genetic relationships and clusters in endemic and non-endemic regions spanning seventeen provinces and two autonomous regions. The findings support multiple locus variable number of tandem repeat (VNTR) analysis as a useful tool in uncovering characteristic patterns across the multiethnic and divergent geographic landscape of China. Several scenarios of clustering of leprosy from township to provincial to regional levels were recognized, while recent occupational or remote migration showed geographical separation of certain strains. First, prior studies indicated that of the four major M. leprae subtypes defined by single nucleotide polymorphisms (SNPs), only type 3 was present in China, purportedly entering from Europe/West/Central Asia via the Silk Road. However, this study revealed VNTR linked strains that are of type 1 in Guangdong, Fujian and Guangxi in southern China. Second, a subset of VNTR distinguishable strains of type 3, co-exist in these provinces. Third, type 3 strains with rpoT VNTR allele of 4, detected in Japan and Korea were discovered in Jiangsu and Anhui in the east and in western Sichuan bordering Tibet. Fourth, considering the overall genetic diversity, strains of endemic counties of Qiubei, Yunnan; Xing Yi, Guizhou; and across Sichuan in southwest were related. However, closer inspection showed distinct local strains and clusters. Altogether, these insights, primarily derived from VNTR typing, reveal multiple and overlooked paths for spread of leprosy into, within and out of China and invoke attention to historic maritime routes in the South and East China Sea. More importantly, new concepts and approaches for prospective case finding and tracking of leprosy from county to national level have been introduced.

Purpose The present study investigated the role of β-hCG in predicting reproductive outcomes and established optimal β-hCG cutoff values in women undergoing cleavage embryo transfer. Methods The patients were transferred with fresh or frozen-thawed embryos and had serum β-hCG levels tested on the 14th day post-embryo transfer. Serum β-hCG levels were compared between different groups. Different cutoff values of β-hCG were established and used to divide the patients into different groups. Reproductive outcomes between groups based on β-hCG levels were compared. Results Significant discrepancies in general characteristics were observed in the subgroups. The cutoff values of β-hCG for predicting the presence/absence of pregnancy, biochemical pregnancy/clinical pregnancy, presence/absence of adverse pregnancy outcomes, and singleton/twin live birth in the cleavage groups were 89.6, 241.1, 585.9, and 981.1 mIU/L, respectively. Biochemical pregnancy rates and adverse pregnancy outcome rates significantly decreased from the low β-hCG group to the higher β-hCG group in sequence. Significantly higher full-term live birth rates were observed in the highest β-hCG group (P < 0.001). Conclusion Serum β-hCG levels were strongly associated with reproductive outcomes. However, the interpretation of β-hCG levels must consider the number and quality of embryos and transfer protocols. When β-hCG was tested on a fixed day post-ET, different cutoff values were required for the prediction of early clinical outcomes. The association between β-hCG and obstetric outcomes must be investigated.