ABSTRACT
Type 2 diabetes (T2D) is characterized by the malfunction of pancreatic β cells. Susceptibility and pathogenesis of T2D can be affected by multiple factors, including sex differences. However, the mechanisms underlying sex differences in T2D susceptibility and pathogenesis remain unclear. Using single-cell RNA sequencing (scRNA-seq), we demonstrate the presence of sexually dimorphic transcriptomes in mouse β cells. Using a high-fat diet-induced T2D mouse model, we identified sex-dependent T2D altered genes, suggesting sex-based differences in the pathological mechanisms of T2D. Furthermore, based on islet transplantation experiments, we found that compared to mice with sex-matched islet transplants, sex-mismatched islet transplants in healthy mice showed down-regulation of genes involved in the longevity regulating pathway of β cells. Moreover, the diabetic mice with sex-mismatched islet transplants showed impaired glucose tolerance. These data suggest sexual dimorphism in T2D pathogenicity, indicating that sex should be considered when treating T2D. We hope that our findings could provide new insights for the development of precision medicine in T2D.
ABSTRACT
Objective:To investigate the clinical treatment of large segmental humeral defects with unilateral external fixation and bone transport.Methods:A retrospective study was conducted of the 9 patients who had been treated at Department of Orthopedics, Shenzhen People's Hospital for large segmental humeral defects from September 2017 to June 2019. They were 5 males and 4 females with an average age of 29 years (from 21 to 41 years). Their defects were caused by trauma in 2 cases, by chronic osteomyelitis in 6 cases and by bone tumor in one case. The length of bone defect ranged from 4.2 to 9.0 cm, with an average of 5.9 cm. A unilateral external fixator was placed in operation, and adjusted regularly 7 to 10 days after operation for bone transport and bone lengthening to restore the length of humerus gradually. The external fixation bracket was removed after 3 to 4 layers of cortex were observed on X-ray films. Recorded were length and rate of humeral lengthening, fracture healing time, time for carrying external fixator and complications; the Disabilities of the Arm, Shoulder and Hand (DASH) scores were compared between preoperation and 15 months postoperation.Results:All the patients were followed up for 15 to 36 months (mean, 19 months). The length of lengthening averaged 5.9 cm (from 4.2 to 9.0 cm) with an average lengthening rate of 26%, the healing index 31 d/cm, the bone healing time 8.3 months, and the time for carrying external fixator 10.8 months(from 8.0 to 13.5 months). Their average DASH scores improved significantly from 25.0 ± 2.4 preoperation to 12.0 ± 1.8 at 15 months postoperation ( P<0.05). Good correction of large humeral defects was achieved in all but one case who reported temporary radial nerve paralysis. There were no such complications as neurovascular injury. The shoulder and elbow functions were basically normal after operation. Conclusions:In the treatment of large segmental humeral defects, unilateral external fixation plus bone transport can quickly repair the defects and recover the upper limb function of the patients.