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Objective·To screen mutations of key genes in the leptin-melanocyte stimulating hormone (LEP-MSH) pathway by whole-exome sequencing (WES) in the obese cohort.Methods·A total of 119 obese patients aged 17－65 years old with body mass index (BMI)≥34 kg/m2, who underwent laparoscopic sleeve gastrectomy from January 2011 to July 2019 at Shanghai Sixth People′s Hospital, Shanghai Jiao Tong University School of Medicine were collected. The peripheral blood samples of the research subjects were collected, and whole genome DNA was extracted to perform WES. Bioinformatic methods were applied to detect the mutations in 16 genes in the LEP-MSH pathway (ADCY3, AGRP, BDNF, KSR2, LEP, LEPR, MC3R, MC4R, MCHR1, MRAP2, NTRK2, PCSK1, PHIP, POMC, SH2B1, and SIM1). Rare variants with the minor allele frequency in the total population less than 0.02 and in the East Asian population less than 0.01 in the 1000 Genome (1000G), Exome Aggregation Consortium (ExAC) and Genome Aggregation Database (gnomAD) were selected for subsequent analysis. Six pieces of prediction software were used to evaluate the deleteriousness of the mutations. Finally, based on the clinical information of each patient, the pathogenicity of all variants was determined according to the guidelines of America College of Medical Genetics and Genomics (ACMG), and only the "pathogenic", "likely pathogenic", and "uncertain significance" variants were retained.Results·A total of 26 variants, 22 kinds of variants were detected in 24 patients from 119 subjects, all of which were heterozygous mutations. The detected variants included 7 in SH2B1 gene (accounting for 26.92% of the total variants), 4 in MCHR1 gene (accounting for 15.38%), 3 in PHIP gene (accounting for 11.53%), 2 in ADCY3 and LEPR genes (accounting for 7.69%, respectively), and 1 in LEP, NTRK2, AGRP, KSR2, MC3R, MC4R, BDNF, and PCSK1 genes, respectively (accounting for 3.85%, respectively). There were 3 patients having the same mutation site in SH2B1 gene, and 2 patients having the same mutation sites in LEPR gene and MCHR1 gene, respectively. In addition, among these mutations, there were 12 ones not included in the East Asian population in 3 public databases, which were novel mutations in the East Asian population, located in SH2B1 (p.V209I, p.R67C, and p.L149F), KSR2 (p.P155T), LEP (p.D106N), LEPR (p.W132R), PHIP (p.K1461R), BDNF (p.N84S), PCSK1 (p.R282W), NTRK2 (p.T732M), MC3R (p.S71P), and MC4R (p.W174X).Conclusion·A total of 22 kinds of rare variations possibly associated with obesity in the LEP-MSH pathway are detected, 12 of which are novel in the East Asian population.

The article reports that due to the scarcity of medical resources in China, very often patients with diabetes do not get enough diabetes education from the clinic, while those in rural areas or ethnic minority groups have less access to education and support. Topics include examines results of previous studies have indicated that mobile health applications are feasible tools for improving self management of diabetes.

Medical imaging contrast agents that are able to provide detailed biological information have attracted increasing attention. Among the new emerging imaging contrast agents, 19 F magnetic resonance imaging contrast agents ( 19 F MRI CAs) are extremely promising for their weak background disturbing signal from the body. However, to prepare 19 F MRI CAs with a long T 2 relaxation time and excellent biocompatibility in a simple and highly effective strategy is still a challenge. Herein, we report a new type of 19 F MRI hydrogel nanocontrast agents ( 19 F MRI HNCAs) synthesized by a surfactant-free emulsion polymerization with commercial fluorinated monomers. The T 2 relaxation time of 19 F MRI HNCA-1 was found to be 25-40 ms, guaranteeing its good imaging ability in vitro . In addition, according to an investigation into the relationship between the fluorine content and 19 F MRI signal intensity, the 19 F MRI signal intensity was not only determined by the fluorine content in 19 F MRI HNCAs but also by the hydration microenvironment around the fluorine atoms. Moreover, 19 F MRI HNCAs demonstrated excellent biocompatibility and imaging capability inside cells. The primary exploration demonstrated that 19 F MRI HNCAs as a new type of 19 F MRI contrast agent hold potential for imaging lesion sites and tracking cells in vivo by 19 F MRI technology., Competing Interests: The authors declare they have no competing financial interests., (This journal is © The Royal Society of Chemistry.)