The impairment in diabetic wound healing represents a significant clinical problem. Chronic inflammation is thought to play a central role in the pathogenesis of this impairment. We have previously shown that treatment of diabetic murine wounds with mesenchymal stem cells (MSCs) can improve healing, but the mechanisms are not completely defined. MicroRNA-146a (miR-146a) has been implicated in regulation of the immune and inflammatory responses. We hypothesized that abnormal miRNA-146a expression may contribute to the chronic inflammation. To test this hypothesis, we examined the expression of miRNA-146a and its target genes in diabetic and nondiabetic mice at baseline and after injury. MiR-146a expression was significantly downregulated in diabetic mouse wounds. Decreased miR-146a levels also closely correlated with increased gene expression of its proinflammatory target genes. Furthermore, the correction of the diabetic wound-healing impairment with MSC treatment was associated with a significant increase in the miR-146a expression level and decreased gene expression of its proinflammatory target genes. These results provide the first evidence that decreased expression of miR-146a in diabetic wounds in response to injury may, in part, be responsible for the abnormal inflammatory response seen in diabetic wounds and may contribute to wound-healing impairment.

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Summary The long-term outcomes of robotic-assisted McKeown esophagectomy (RAME) compared to thoraco-laparoscopic McKeown esophagectomy (TLME) for the patients with esophageal squamous cell carcinoma (ESCC) remain unclear. The aim of this study was to compare the number of dissected lymph nodes and long-term survival between RAME and TLME using a propensity score-matched (PSM) analysis. A total of 721 patients undergoing minimally invasive McKeown esophagectomy at our department from February 2015 to October 2019 were analyzed, including 310 patients in RAME group and 411 in TLME group. The exact numbers of lymph nodes including those among thoracic and abdominal categories as well as those along the recurrent laryngeal nerve (RLN) were all recorded. PSM analysis was applied to generate matched pairs for further comparison. All patients with R0 resection were followed with a strict follow-up period which range from 1 to 56 months. The effect of lymphadenectomy was compared between all patients in unmatched and matched groups. Long-term outcomes consisting of overall survival (OS), disease-free survival (DFS) and recurrence rate (including regional recurrence rate, systemic recurrence rate and mediastinal lymph nodes recurrence rate) were compared in R0 resection patients. Finally, 292 patients were identified for each cohort after PSM. RAME was found to yield significantly more left RLN lymph nodes (mean: 2.27 ± 0.90 vs. 2.09 ± 0.79; P = 0.011) and more thoracic lymph nodes (mean: 12.60 ± 4.22 vs. 11.83 ± 3.12, P = 0.012) compared with TLME after PSM analysis. There was no significant difference in the OS and DFS between the RAME and TLME group. Besides, total recurrences were recognized in 33 (11.7%) patients in the RAME group and 36 (12.9%) in the TLME group (P = 0.676). The mediastinal lymph nodes recurrence rate in the RAME group was tended to be lower than that in the TLME group (2.5% vs. 5.4%, P = 0.079). Therefore, RAME might be an alternative approach for the treatment of ESCC with more lymph nodes dissected and similar long-term survival outcomes compared to TLME.

Recurrent tracheoesophageal fistula (rTEF) is a complex complication after the repair of esophageal atresia (EA) and remains a challenge because of difficulties in preoperative management and the substantial rates of mortality and morbidity after reoperation. By reviewing a single institution's experience in the management of rTEF and assessing the outcome, we aimed to provide an optimal approach for managing rTEF and to evaluate growth and feeding problems after reoperations. The medical records of 35 patients with rTEF treated at a single institution from June 2012 to December 2015 were reviewed, and follow-up data were collected from all survivors. The diagnosis of rTEF was made using a modified esophagram in 32 of 35 patients. Before reoperation, all patients received continuous aspiration to prevent reflux and aspiration pneumonia by placing two nasogastric tubes at the level of the fistula and into the stomach, and they received enteral nutrition through a jejunal feeding tube. Thirty-five patients received a total of 41 reoperations, including 12 operations of fistula resection, 28 reanastomosis, and 1 esophageal replacement. The incidence of postoperative anastomotic leak (AL), anastomotic stricture (AS), and repeat recurrences was 40.0%, 17.1%, and 11.4%, respectively. The mortality rate was 8.6%. All survivors achieved full oral intake. Mid-term follow-up (median of 18 months) revealed that 7 (21.9%) presented prolonged meal time, 6 (18.8%) had feeding refusal, 8 (25.0%) experienced coughing during feeding, and 7 (21.9%) had vomiting during feeding. According to the growth data, 5 survivors (15.6%) presented with growth retardation, including stunting (n = 1), wasting (n = 2), and underweight (n = 2). The modified esophagram is an effective and reliable method for diagnosing rTEF. Optimized preoperative management and surgical techniques lead to a satisfactory outcome. Nevertheless, nutritional evaluation and feeding guidance by a nutritionist after reoperation are recommended.

The impairment in diabetic wound healing represents a significant clinical problem. Decreased angiogenesis is thought to play a central role in the pathogenesis of this impairment. We have previously shown that treatment of diabetic murine wounds with mesenchymal stem cells can improve healing, but the mechanisms are not completely defined. MicroRNA-15b (miR-15b) has been implicated in the regulation of the angiogenic response. We hypothesized that abnormal miR-15b expression may contribute to the impaired angiogenesis observed in impaired diabetic wound healing. To test this hypothesis, we examined the expression of miR-15b and its target genes in diabetic and nondiabetic mice before and after injury. MiR-15b expression was significantly up-regulated in diabetic mouse wounds during the wound healing response. Increased miR-15b levels also closely correlated with decreased gene expression of its proangiogenic target genes. Furthermore, the correction of the diabetic wound healing impairment with mesenchymal stem cell treatment was associated with a significant decrease in miR-15b expression level and increased gene expression of its proangiogenic target genes. These results provide the first evidence that increased expression of miR-15b in diabetic wounds in response to injury may, in part, be responsible for the abnormal angiogenic response seen in diabetic wounds and may contribute to the observed wound healing impairment.

Previous studies have shown that bovine lactoferrin (bLF) exerts antibacterial, immune-modulating and anti-inflammatory effects. The present study aimed to investigate the effect of enteral bLF supplementation on intestinal adaptation and barrier function in a rat model of short bowel syndrome (SBS). Male Sprague -Dawley rats aged 4 weeks were randomised into three groups (n 10 per group): Sham group (rats submitted to bowel transection and reanastomosis); SBS group (rats submitted to 80 % small-bowel resection); SBSbLF group (rats submitted to 80 % small-bowel resection plus treatment with bLF (0·5 g/kg per d) by oral administration from day 2 to day 20). Despite similar food intake, both the SBS and SBS-bLF groups exhibited significantly lower body weight gain, but increased villus height and crypt depth and a higher intestinal epithelial cell proliferation index (P,0·05) when compared with the Sham group. Compared with that in the SBS group, in the SBS-bLF group, bacterial translocation to regional organs was low and intestinal permeability was significantly reduced. The SBS-bLF group also had increased secretory IgA (sIgA) concentrations in ileal contents (29·9 (23·8 -33·0) ng/ ml), when compared with the other two groups having similar sIgA concentrations (17·5 (12·6-29·1) and 19·3 (11·5-27·0) ng/ml, respectively). The relative expression levels of two tight junction (TJ) proteins, occludin and claudin-4, in the SBS-bLF group were significantly higher than those in the SBS group (P,0·05), but did not exhibit any significant differences when compared with those in the Sham group. In conclusion, enteral bLF supplementation up-regulates small-bowel sIgA concentrations and TJ protein expression and reduces intestinal permeability and could thus support intestinal barrier integrity and protect against bacterial infections in SBS.

We have previously demonstrated that the small molecule octadecenyl thiophosphate (OTP), a synthetic mimic of the growth factor-like mediator lysophosphatidic acid (LPA), showed radioprotective activity in a mouse model of total-body irradiation (TBI) when given orally or intraperitoneally 30 min before exposure to 9 Gy γ radiation. In the current study, we evaluated the effects of OTP, delivered subcutaneously, for radioprotection or radiomitigation from −24 h before to up to +72 h postirradiation using a mouse TBI model with therapeutic doses at around 1 mg/kg. OTP was injected at 10 mg/kg without observable toxic side effects in mice, providing a comfortable safety margin. Treatment of C57BL/6 mice with a single dose of OTP over the time period from −12 h before to +26 h after a lethal dose of TBI reduced mortality by 50%. When administered at +48 h to +72 h postirradiation (LD50/30 to LD100/30), OTP reduced mortality by ≥34%. OTP administered at +24 h postirradiation significantly elevated peripheral white blood cell and platelet counts, increased crypt survival in the jejunum, enhanced intestinal glucose absorption and reduced endotoxin seepage into the blood. In the 6.4–8.6 Gy TBI range using LD50/10 as the end point, OTP yielded a dose modification factor of 1.2. The current data indicate that OTP is a potent radioprotector and radiomitigator ameliorating the mortality and tissue injury of acute hematopoietic as well as acute gastrointestinal radiation syndrome.

The present study aimed to determine the characteristics of multifidus, erector spinae and psoas major degeneration in elderly patients with degenerative lumbar scoliosis (DLS) and the correlation between asymmetric changes and patient quality of life. A total of 49 patients with lumbar scoliosis (DLS group) and 38 healthy individuals (control group) were prospectively examined. The functional cross-sectional area, cross-sectional area difference index (CDI) and fat infiltration rate (FIR) of the multifidus, erector spinae and psoas major at the apical vertebral level were measured using MRI. The visual analogue scale (VAS) score, Oswestry Disability Index (ODI) and 36-item Short Form Health Survey (SF-36) score were used to evaluate patient quality of life. Correlations between the degree of asymmetric muscular degeneration and quality of life were analysed. The CDI of the multifidus, erector spinal and psoas major was higher in the DLS group compared with that in the control group. The CDI of the multifidus was found to be positively associated with the Cobb angle of lumbar scoliosis. Similar results were obtained for fat infiltration between the two groups. In addition, the CDI and FIR difference index of the multifidus was positively correlated with the VAS score and ODI but negatively correlated with the SF-36 score. The quality of life significantly decreased with increasing asymmetric atrophy and fat infiltration in the multifidus. Thus, strategies to enhance the function of the multifidus may have a positive impact on quality of life (Chinese Clinical Trial Registry, registration date, 2018.11.12; registration no. ChiCTR1800019459.).