SNP-based and haplotype-based genome-wide association on drug dependence in Han Chinese.

BACKGROUND: Drug addiction is a serious problem worldwide and is influenced by genetic factors. The present study aimed to investigate the association between genetics and drug addiction among Han Chinese. METHODS: A total of 1000 Chinese users of illicit drugs and 9693 healthy controls were enrolled and underwent single nucleotide polymorphism (SNP)-based and haplotype-based association analyses via whole-genome genotyping. RESULTS: Both single-SNP and haplotype tests revealed associations between illicit drug use and several immune-related genes in the major histocompatibility complex (MHC) region (SNP association: log10BF = 15.135, p = 1.054e-18; haplotype association: log10BF = 20.925, p = 2.065e-24). These genes may affect the risk of drug addiction via modulation of the neuroimmune system. The single-SNP test exclusively reported genome-wide significant associations between rs3782886 (SNP association: log10BF = 8.726, p = 4.842e-11) in BRAP and rs671 (SNP association: log10BF = 7.406, p = 9.333e-10) in ALDH2 and drug addiction. The haplotype test exclusively reported a genome-wide significant association (haplotype association: log10BF = 7.607, p = 3.342e-11) between a region with allelic heterogeneity on chromosome 22 and drug addiction, which may be involved in the pathway of vitamin B12 transport and metabolism, indicating a causal link between lower vitamin B12 levels and methamphetamine addiction. CONCLUSIONS: These findings provide new insights into risk-modeling and the prevention and treatment of methamphetamine and heroin dependence, which may further contribute to potential novel therapeutic approaches.

Post-treatment With Irisin Attenuates Acute Kidney Injury in Sepsis Mice Through Anti-Ferroptosis via the SIRT1/Nrf2 Pathway.

Kidney is one of the most vulnerable organs in sepsis, resulting in sepsis-associated acute kidney injury (SA-AKI), which brings about not only morbidity but also mortality of sepsis. Ferroptosis is a new kind of death type of cells elicited by iron-dependent lipid peroxidation, which participates in pathogenesis of sepsis. The aim of this study was to verify the occurrence of ferroptosis in the SA-AKI pathogenesis and demonstrate that post-treatment with irisin could restrain ferroptosis and alleviate SA-AKI via activating the SIRT1/Nrf2 signaling pathway. We established a SA-AKI model by cecal ligation and puncture (CLP) operation and an in vitro model in LPS-induced HK2 cells, respectively. Our result exhibited that irisin inhibited the level of ferroptosis and ameliorated kidney injury in CLP mice, as evidenced by reducing the ROS production, iron content, and MDA level and increasing the GSH level, as well as the alteration of ferroptosis-related protein (GPX4 and ACSL4) expressions in renal, which was consistent with the ferroptosis inhibitor ferrostatin-1 (Fer-1). Additionally, we consistently observed that irisin inhibited ROS accumulation, iron production, and ameliorated mitochondrial dysfunction in LPS-stimulated HK-2 cells. Furthermore, our result also revealed that irisin could activate SIRT1/Nrf2 signaling pathways both in vivo and vitro. However, the beneficial effects of irisin were weakened by EX527 (an inhibitor of SIRT1) in vivo and by SIRT1 siRNA in vitro. In conclusion, irisin could protect against SA-AKI through ferroptotic resistance via activating the SIRT1/Nrf2 signaling pathway.

The safety and efficacy of esketamine in comparison to dexmedetomidine during drug-induced sleep endoscopy in children with obstructive sleep apnea hypopnea syndrome: A randomized, controlled and prospective clinical trial.

Background and Purpose: Data and high-quality studies of anesthetic methods for children with obstructive sleep apnea hypopnea syndrome (OSAHS) who undergo drug-induced sleep endoscopy (DISE) are limited. Research on pediatric DISE using esketamine has never been reported before. To test the safety and efficacy of esketamine during DISE in children with OSAHS, we compare esketamine (Group K) with dexmedetomidine (Group D) in this study. Methods: 100 children with ASA Ⅰ∼Ⅱ grade, prepared for an elective adenotonsillectomy under general anesthesia, were enrolled in this study and randomized into two groups. Midazolam 0.1 mg/kg was administered intravenously for both groups. In Group D a 1 µg/kg bolus of dexmedetomidine was given over 10 min followed by the infusion rate 1 µg/kg/hr to the end of DISE. Group K received a 1.0 mg/kg IV bolus of esketamine over 10 s followed by the infusion rate 1 mg/kg/hr to the end of DISE. Results: Group K had a higher percentage of success than Group D (p = 0.008). The onset time of Group K was shorter than that of Group D (p = 0.000). The University of Michigan Sedation Scale (UMSS) score of Group K was higher than that of Group D (p = 0.005). The risk of adverse effects (AEs) was lower in Group K (p = 0.000). In Group D, systolic and diastolic blood pressure (SBP and DBP) and heart rate (HR) all decreased, while in Group K, SBP, DBP, and HR hardly changed. Conclusion: Esketamine in comparison to dexmedetomidine provides more effective and safer depth of anesthesia for OSAHS pediatric DISE by ensuring short onset time, deep sedation, and few AEs. Clinical Trial Registration: ClincalTrials.gov, identifier NCT04877639.

[Horn shaped perforator flap pedicled with the angular artery: anatomy basis and clinical application].

OBJECTIVE: To explore the anatomic basis and clinical application of the horn shaped perforator flap pedicled with the angular artery for the reconstruction of midface defect. METHODS: (1) 10 fresh cadavers were perfused with a modified guiding oxide gelatin mixture for three-dimensional visualization reconstruction using a 16-slice spiral computed tomography scanner and specialized software (Materiaise' s interactive medical image control system, MIMICS). The origin and distribution of the angular artery perforator were observed. (2) Between July 2012 and July 2014, twenty-one patients underwent operations for the reconstruction of midface defect. Ten patients had squamous cell carcinoma, nine patients had basal cell carcinoma and two patients had nevus. The flaps' size ranged from 1.5 cm x 3.5 cm to 2.5 cm x 5.0 cm. RESULTS: The facial artery branches the lateral nasal artery 1 cm from the outside corner of the mouth, subsequently strenches to inner canthus continuing as the angular artery. The angular artery anastomoses extensively with the dorsal nasal artery and the infraorbital artery. All the flaps survived. The patients were satisfied with the final aesthetic and functional results. CONCLUSIONS: The flap can be designed flexibly and simply with reliable blood supply. The donor sites could be closed directly without skin graft, it is a simple and fast method for the reconstruction of midface defect.

Socioeconomic profile of diabetic patients with and without foot problems.

INTRODUCTION: To identify the differences in a socioeconomic profile between two cohorts of diabetic patients - one with diabetic foot problems and another without diabetic foot problems. MATERIALS AND METHODS: The cohort with diabetic foot problems (including cellulitis, abscess, osteomyelitis, septic arthritis, gangrene, ulcers, or Charcot joint disease) consisted of 122 diabetic patients, while the other cohort without foot problems consisted of 112 diabetic patients. Both were seen at the National University Hospital from January to April 2007. A detailed protocol was designed and the factors studied included patient profile, average monthly household income, education, compliance to diabetic medication, attendance at clinics for diabetic treatment, exercise, smoking, alcohol consumption, gender, and glycosylated haemoglobin (HbA1(C)) level. These were studied for significant differences using univariate and stepwise multivariate logistic regression analysis. RESULTS: With multivariate analysis, Malay ethnicity (p<0.001), education of up to secondary school only (p=0.021), low average monthly household income of less than SGD $2,000 (p=0.030), lack of exercise (at least once a week, p=0.04), and elevated HbA1(C) level (>7.0%; p=0.015) were found to be significantly higher in the cohort with diabetic foot problems than the cohort without. CONCLUSIONS: There are significant differences in the socioeconomic factors between diabetic patients with diabetic foot problems and those without.