Pyridoxamine ameliorates methylglyoxal-induced macrophage dysfunction to facilitate tissue repair in diabetic wounds

Methylglyoxal (MGO) is a highly reactive dicarbonyl compound formed during hyperglycaemia. MGO combines with proteins to form advanced glycation end products (AGEs), leading to cellular dysfunction and organ damage. In type 2 diabetes mellitus (T2DM), the higher the plasma MGO concentration, the higher the lower extremity amputation rate. Here, we aimed to identify the mechanisms of MGO-induced dysfunction. We observed that the accumulation of MGO-derived AGEs in human diabetic wounds increased, whereas the expression of glyoxalase 1 (GLO1), a key metabolic enzyme of MGO, decreased. We show for the first time that topical application of pyridoxamine (PM), a natural vitamin B6 analogue, reduced the accumulation of MGO-derived AGEs in the wound tissue of type-2 diabetic mice, promoted the influx of macrophages in the early stage of tissue repair, improved the dysfunctional inflammatory response, and accelerated wound healing. In vitro, MGO damaged the phagocytic functions of M1-like macrophages induced by lipopolysaccharide (LPS), but not those of M0-like macrophages induced by PMA or of M2-like macrophages induced by interleukins 4 (IL-4) and 13 (IL-13); the impaired phagocytosis of M1-like macrophages was rescued by PM administration. These findings suggest that the increase in MGO metabolism in vivo might contribute to macrophage dysfunction, thereby affecting wound healing. Our results indicate that PM may be a novel therapeutic approach for treating diabetic wounds. MGO forms protein adducts that cause macrophage dysfunction. These adducts cause cell and organ dysfunction that is common in diabetes. Pyridoxamine scavenges MGO to ameliorate this dysfunction, promoting wound healing. Pyridoxamine could be used therapeutically to treat non-healing diabetic wounds.     

硬化大脑中动脉及豆纹支管壁弹性结构改变及意义

本文用光镜、电镜观察了正常和硬化大脑中动脉及其豆纹支管壁弹性结构的形态。结果显示，硬化大脑中动脉内弹力膜断裂，且以外层断裂明显，波纹状外观消失；而豆纹支内弹力膜结构完整，波纹状外观清晰可见。平滑肌萎缩、变性，胶原纤维增多。提示硬化大脑中动脉破裂出血是内弹力膜破坏，平滑肌萎缩，管壁脆性增加所致；而豆纹动脉是根部存在＂中膜缺损＂，此外受血流冲击引起破裂的可能性大。     

Meta-analysis suggests that reverse shoulder arthroplasty in proximal humerus fractures is a better option than hemiarthroplasty in the elderly

Purpose

This systematic meta-analysis and review aims to critically compare the outcome of reverse shoulder arthroplasty versus hemiarthroplasty for the treatment of complex proximal humeral fracture.

Methods

Relevant original studies were searched in the electronic databases of Medline, Embase, Cochrane central database and China National Knowledge Infrastructure (CNKI) (all through December 2014). Studies that investigated and compared the effectiveness or complications in both groups and provided sufficient data of interest were included in this meta-analysis. Participants in both groups were significantly the same in the demography and injury mechanism.

Results

Eight studies that fulfilled inclusion and exclusion criteria were included in this meta-analysis, which included 421 participants in hemiarthroplasty (HA) and 160 in reverse shoulder arthroplasty (RSA). Patients were followed-up for at least one year in each study. Compared with HA, RSA was associated with a lower rate of total complications, higher American Shoulder and Elbow Surgeons (ASES) score, more healed tuberosities and improved active forward elevation. Both treatments were comparable in term of revision surgeries, mortality, subjective satisfaction and active external rotation.

Conclusions

The present evidence from this meta-analysis suggested that RSA was a more advantaged method for the treatment of complex proximal humeral fractures. Clinical decision should be preferred to RSA on the condition that patients’ medical conditions are indicated.

     

Comparison of renal function detriments after local tumor ablation or partial nephrectomy for renal cell carcinoma

Purpose

Local tumor ablation (LTA) and partial nephrectomy (PN) represent treatment alternatives for patients diagnosed with small renal mass and both may result in renal function detriments. The aim of the study was to compare renal function detriments after LTA or PN.

Methods

A Surveillance epidemiology and End Results-Medicare-linked retrospective cohort of 2850 T1 kidney cancer patients who underwent LTA or PN was abstracted. Short-term outcomes consisted of 30-day acute kidney injury (AKI) and 30-day dialysis rates. Long-term outcomes consisted of episodes of AKI, mild and moderate–severe chronic kidney disease (CKD), end-stage renal disease, hemodialysis and anemia in CKD. Analyses consisted of propensity score matching, logistic and Cox regression.

Results

After propensity score matching, 1122 patients remained. The 30-day incidence of AKI was 4.6 % after LTA and 9.4 % after PN. In multivariable analyses (MVAs), LTA was associated with a lower AKI rate (OR 0.42; p = 0.001). The 30-day incidence of any dialysis was <2 % after either LTA or PN. In MVA, LTA was not associated with a lower rate of any dialysis (OR 0.43; p = 0.2). At long-term assessment, both the unadjusted and adjusted rates of all six examined end points were not different between LTA and PN (all p > 0.5).

Conclusions

LTA offers short-term protective effect from AKI. The short-term rates of any dialysis treatment are similar after either LTA or PN. At long-term assessment, LTA and PN renal function detriment rates are not different. Concern for long-term functional outcomes should not be a barrier for PN.

     

A retrospective study on post-operative hearing of middle ear cholesteatoma patients with labyrinthine fistula

Conclusions: There is no significant change in bone conduction threshold after operation, so the tympanoplasty can be done to maintain hearing when conditions allow. Objective: To study the impact of surgical treatment on hearing of cholesteatoma patients with labyrinthine fistula. Methods: The clinical data of 35 patients (35 ears) with labyrinthine fistula, which were caused by cholesteatoma, were analyzed retrospectively. The hearing of 21 patients was followed up. Results: Three months to 5 years follow-up of 21 patients were accomplished by pure tone audiometry and other details. There was no recurrent cholesteatoma in the patients. Compared with pre-operative average bone conduction at 0.5, 1, 2, 4, and 8 kHz, 12 cases had a difference less than 5 dB, three patients’ hearing improved (more than 10 dB), and five cases declined (more than 10 dB). One patient received cochlear implantation 3 months after the surgery. The average bone and air conduction thresholds at 0.5, 1, 2, 4, and 8 kHz had no obvious change (p?>?0.05) in 11 patients managed by a canal wall down mastoidectomy with tympanoplasty.