[Clinical efficacy of spinal cord stimulation for the patients with diabetic foot].

Objective: To observe the clinical efficacy of spinal cord stimulation (SCS) in the treatment of diabetic foot (DF). Methods: Sixteen patients who were diagnosed with DF and treated with SCS from the Department of Pain Medicine of the First Affiliated Hospital, China Medical University from October 2015 to October 2018 were retrospectively analyzed. Visual analogue scale (VAS), 36-item short form health survey (SF-36), transcutaneous oxygen partial pressure (TcPO2) and skin temperature of lower limbs were compared before and after treatment, and the complications were recorded. Results: Among the 16 patients, 14 were equipped with implantable pulse generator (IPG). The VAS scores decreased significantly from 7.5±1.2 before treatment to 2.6±0.8, 2.0±0.7, 1.6±0.6, 1.0±0.9, 0.9±0.9 at 1 day, 1 week, 3 months, 6 months and 12 months after electrode implantation respectively (all P<0.05). At 12 months after treatment, the parameters of SF-36 were significantly different from those before treatment (all P<0.05). The TcPO2 was (23±5) mmHg before treatment and (38±6) mmHg at 1 week after treatment, with a statistical difference (P<0.05), and the temperature of lower limbs increased significantly (P<0.05). No serious complications were observed in all patients. Conclusion: SCS can relieve the pain of patients with DF, improve the microcirculation and blood supply of lower limbs, and thus promote the quality of life, with rare serious complications.

Effects of aescin on testicular repairment in rats with experimentally induced varicocele.

This study was conducted to investigate the effects of aescin treatment in a rodent model treated with an experimentally induced varicocele. Experimental varicocele was induced by partial ligation of the left renal vein of rats. Aescin administration was performed daily for 4 weeks after the varicocele induction. Seven weeks later, a contrast-enhanced ultrasound was performed of the rats' testis to assess testicular blood flow. The animals were sacrificed, and H&E staining was then used to evaluate testicular pathological changes and polymorphonuclear leucocytes density. Cauda epididymal sperm counts and motility were evaluated. Blood was collected for the measurement of follicle-stimulating hormone, luteinising hormone and testosterone. Contrast-enhanced ultrasound showed that there were significant decreases in testicular blood flow in the aescin-treated groups compared with those in control varicocele group. Testicular oedema was detected in those rats treated with a varicocele but without aescin, while no oedema was found in the experimental group. H&E staining showed dysfunctional spermatogenesis in both cohorts; however, polymorphonuclear leucocytes density was significantly reduced in aescin-treated groups. There was an increase in sperm counts of the aescin-treated groups. Our study demonstrated that aescin could exert therapeutical effects on reversal of testicular lesions in varicocele rats.

Biogenesis, transit, and functional properties of the insulin proreceptor and modified insulin receptors in 3T3-L1 adipocytes. Use of monensin to probe proreceptor cleavage and generate altered receptor subunits.

The biogenesis, intracellular transport, and functional properties of the insulin proreceptor and modified insulin receptors were studied in hormone-responsive 3T3-L1 adipocytes. After control cells were labeled with [35S]Met for 7 min, the principal polypeptide that was precipitated by anti-insulin receptor antibodies had a molecular weight (Mr) of 180 000. This initial precursor was rapidly converted (t1/2 = 35 min) to a 200-kilodalton (kDa) polypeptide, designated the insulin proreceptor, by the apparent posttranslational addition of N-linked, high mannose core oligosaccharide units. Mature alpha (Mr 130 000) and beta (Mr 90 000) subunits were derived from sequences within the proreceptor by proteolytic cleavage and late processing steps, and these subunits appeared on the cell surface 2-3 h after synthesis of the 180-kDa precursor. The cation ionophore monensin was used in combination with metabolic labeling, affinity cross-linking, and external proteolysis to probe aspects of proreceptor function, transit, and the development of insulin sensitivity at the target cell surface. At 5 micrograms/mL, monensin potently inhibited the proteolytic cleavage step, and the 200-kDa polypeptide accumulated. Lower concentrations of the ionophore selectively blocked late processing steps in 3T3-L1 adipocytes so that apparently smaller alpha' (Mr 120 000) and beta' (Mr 85 000) subunits were produced. Proreceptor and alpha' and beta' subunits were translocated to the cell surface, indicating that the signal for intracellular transit occurs in the 200-kDa polypeptide and is independent of the posttranslational proteolysis and late processing steps. The alpha' subunit bound insulin both at the surface of intact cells and after solubilization with Triton X-100; the beta' subunit was phosphorylated in an insulin-stimulated manner. The detergent-solubilized 200-kDa proreceptor also exhibited both functional properties. However, the proreceptor that was transported to and exposed on the cell surface was incapable of binding insulin in intact adipocytes. Thus, late processing is not essential for the expression of functions associated with mature alpha and beta subunits. In contrast, it appears that the proteolytic generation of subunits is required for the correct orientation of the hormone binding site in the plasma membrane bilayer and the development of insulin responsiveness in 3T3-L1 adipocytes.

Latent insulin receptors and possible receptor precursors in 3T3-L1 adipocytes.

Cell surface and cryptic insulin receptors were solubilized from the particulate fraction of murine 3T3-L1 adipocytes with buffer containing 1% Triton X-100. Solubilized receptors were affinity crosslinked with 125I-labeled insulin and disuccinimidyl suberate and characterized by sodium dodecyl sulfate/polyacrylamide gel electrophoresis and autoradiography after specific immunoprecipitation. Two insulin-binding polypeptides were identified: the more abundant protein had a Mr of 130,000, corresponding to the size of the hormone-binding subunit of insulin receptors on the surface of target cells; the second polypeptide exhibited a Mr of 200,000 and appears to be a component of the latent pool because it was unaffected when 3T3-L1 adipocytes were exposed to trypsin under conditions that result in a 95% reduction in cell surface insulin-binding activity and the loss of the Mr 130,000 polypeptide in crosslinking experiments. Unexpectedly, the population of Mr 200,000 molecules in intact cells was accessible for limited cleavage by chymotrypsin, yielding a Mr 195,000 insulin-binding polypeptide. When 3T3-L1 adipocytes received a 15-min pulse of [35S]methionine, the predominant immunoprecipitated polypeptide had a Mr of 180,000. During a 1.5-hr chase, radioactivity in the Mr 180,000 species rapidly declined while the latent Mr 200,000 polypeptide became intensely labeled. After a 5-hr chase period, broad protein bands with Mrs of 130,000 and 90,000 were visualized as the major immunoprecipitated radioactive polypeptides. Thus, the Mr 180,000 species may be a very early biosynthetic precursor that may be subsequently processed to a Mr 200,000 form and one or both of the smaller receptor subunits at the cell surface.