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ObjectiveTo investigate the promotional effect of astragaloside on the repair and healing of chronic non-healing wounds and its mechanism. MethodA total of 60 male SD rats were constructed with full-layer skin defect wounds on the back， and except for the control （Con） group， the rest were constructed with non-healing wounds， which were then randomly divided into the sham-operation （sham） group， the low-dose astragaloside group， the high-dose astragaloside group， the astragaloside + LY294002 ［phosphatidylinositol 3-kinase （PI3K） inhibitor］ group， and the astragaloside + EX527 ［silencing regulatory protein 1 （SIRT1） inhibitor］ group. The percentage of wound area in each group was observed on the 2nd， 4th， 6th， and 8th days after wound molding. Collagen type Ⅰ alpha 1 （COL1A1） and alpha smooth muscle actin （α-SMA） expressions in the wound tissue were detected by immunofluorescence. Hematoxylin and eosin （HE） staining was performed to determine the pathological structure of the wound. The mRNA expression of inflammatory factors in the wound was measured by real-time polymerase chain reaction （Real-time PCR）， and the expression of proteins related to the SIRT1/ nuclear factor （NF）-κB and PI3K/protein kinase B （Akt） signaling pathways in the wound was tested by Western blot. ResultCompared with the sham group， the percentage of postoperative wound area of rats in both low-dose and high-dose astragaloside groups gradually decreased with time， and the efficacy of the high-dose astragaloside group was better. Compared with the Con group， the fluorescence intensity of COL1A1 in wound tissue of the sham group decreased， while the expression of α-SMA increased. The epithelial tissue was severely damaged， with an increase in the thickness， and a large number of inflammatory cells were seen in the infiltration. The mRNA expression of tumor necrosis factor （TNF）-α， interleukin （IL）-1β， IL-6， and inducible nitric oxide synthase （iNOS） was elevated. The protein expression of NF-κB p65， p-PI3K/PI3K， and p-Akt/Akt was elevated， while SIRT1 expression was decreased （P<0.05）. Compared with the sham group， the fluorescence intensity of COL1A1 and α-SMA increased after astragaloside treatment. The number of epithelial cells increased， and the thickness decreased. The inflammatory cells decreased， and the amount of collagen increased. The mRNA expression of TNF-α， IL-1β， IL-6， and iNOS was decreased， and the protein expression of NF-κB p65， p-PI3K/PI3K， and p-Akt/Akt was decreased. SIRT1 was elevated， and the effect was better in the high-dose astragaloside group （P<0.05）. Compared with the high-dose astragaloside group， inhibition of the PI3K/Akt and SIRT1 pathways by LY294002 and EX527 prevented the therapeutic efficacy of astragaloside on chronic non-healing wounds. ConclusionThe topical application of astragaloside significantly promotes the healing of chronic non-healing wounds in rats， and the mechanism may be related to the activation of the PI3K/Akt pathway and the SIRT1/NF-κB pathway.
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Cyanobacteria are the only prokaryotes capable of oxygenic photosynthesis, which have potential to serve as "autotrophic cell factories". However, the synthesis of biofuels and chemicals using cyanobacteria as chassis are suffered from poor stress tolerance and low yield, resulting in low economic feasibility for industrial production. Thus, it's urgent to construct new cyanobacterial chassis by means of synthetic biology. In recent years, adaptive laboratory evolution (ALE) has made great achievements in chassis engineering, including optimizing growth rate, increasing tolerance, enhancing substrate utilization and increasing product yield. ALE has also made some progress in improving the tolerance of cyanobacteria to high light intensity, heavy metal ions, high concentrations of salt and organic solvents. However, the engineering efficiency of ALE strategy in cyanobacteria is generally low, and the molecular mechanisms underpinning the tolerance to various stresses have not been fully elucidated. To this end, this review summarizes the ALE-associated technical strategies and their applications in cyanobacteria chassis engineering, following by discussing how to construct larger ALE mutation library, increase mutation frequency of strains and shorten evolution time. Moreover, exploration of the construction principles and strategies for constructing multi-stress tolerant cyanobacteria, and efficient analysis the mutant libraries of evolved strains as well as construction of strains with high yield and strong robustness are discussed, with the aim to facilitate the engineering of cyanobacteria chassis and the application of engineered cyanobacteria in the future.
Subject(s)
Technology , Photosynthesis/genetics , Cyanobacteria/genetics , Light , BiofuelsABSTRACT
Objective:To investigate the short-term clinical outcomes of posterior percutaneous pedicle screw fixation combined with percutaneous vertebroplasty (PVP) for treating Kümmell's disease with intravertebral instability.Methods:A retrospective case series study was made on 18 patients with Kümmell's disease with intravertebral instability treated at Lishui Hospital of Zhejiang University from January 2012 to February 2016. There were 4 males and 14 females, aged 65-86 years [(76.0±5.5)years]. Segment of injury was T 7 in 1 patient, T 10 in 2, T 11 in 3, T 12 in 4, L 1 in 6, and L 2 in 2. All patients underwent posterior percutaneous pedicle screw fixation combined with PVP. The operation time, intraoperative blood loss, amount of cement injected into the vertebra, and length of postoperative hospital stay were recorded. The visual analogue scale (VAS), Oswestry disability index (ODI), Cobb angle, and wedge angle of the operative segment were recorded and compared preoperatively, postoperatively, and at the latest follow-up. Meanwhile, the complications were recorded. Results:All patients were followed up for 12-28 months [(17.7±4.4)months]. The operation time was 110-175 minutes [(137.9±21.9)minutes] and the blood loss was 50-165 ml [(110.7±35.6)ml]. The amount of cement injected into the vertebra was 2.5-6.0 ml [(4.7±0.9)ml]. The length of hospital stay was 7-14 days [(9.4±2.3)days]. The VAS was (7.8±1.2) points preoperatively, (3.3±0.7) points at 1 week postoperatively and (2.4±0.7)points at the latest follow-up. The ODI was (67.3±7.3)% preoperatively, (30.5±7.5)% at 1 week postoperatively and (21.8±8.3)% at the latest follow-up. The Cobb angle was (26.2±9.5)° preoperatively, (12.6±7.2)° at 1 week postoperatively and (16.7±6.2)°at the latest follow-up. The wedge angle was (21.1±6.1)° preoperatively, (8.4±4.6)° at 1 week postoperatively, and (13.2±4.1)° at the latest follow-up. The above clinical and radiological parameters were significantly improved after operation ( P<0.05), and showed no significant differences at the latest follow-up when compared to that at 1 week postoperatively ( P>0.05). Five patients showed slight screw loosening, but there was no obvious dislocation of internal fixation. One case developed distal vertebral compression fracture at 6 months postoperatively and cured after a second PVP. Conclusion:For Kümmell's disease with intravertebral instability, posterior percutaneous pedicle screw fixation combined with PVP can effectively restore and maintain the spinal sequence, rapidly relieve the pain and improve clinical function. However, the long-term efficacy needs further study.
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Objective:After the propensity score matching method was used to balance the covariates between groups, the effects of pancreaticoduodenectomy (PD) and total pancreatectomy (TP) on the survival of patients with pancreatic head cancer and related prognostic factors were compared.Methods:The National Cancer Institute Surveillance, Epidemiology and Results (SEER) database were searched and 3 676 patients with pancreatic head cancer from 2010 to 2016 were selected, of whom 3 559 patients underwent PD (PD group) and 117 patients underwent TP (TP group) . Using propensity score matching to balance confounding factors, 117 pairs of cases from PD group and TP group were matched successfully. The Kaplan-Meier curve was used to observe the overall survival rate and cancer-specific survival rate of patients before and after matching. Log-rank test and Cox proportional hazard model were used to analyze and evaluate the impact of different clinicopathological characteristics on the prognosis of patients with pancreatic head cancer.Results:Before matching, the 1, 3, and 5-year cancer-specific survival rates of 3 559 patients in the PD group were 72.8%, 35.1% and 24.9%, and the median survival time was 23.89 months; the 1, 3, and 5-year cancer-specific survival rates of 117 patients in the TP group were 67.9%, 29.4% and 26.1%, and the median survival time was 21.51 months, and all the differences were not statistically significant (all P>0.05). After matching, the 1, 3, and 5-year cancer-specific survival rates of 117 patients in the PD group were 77.8%, 44.5% and 31.8%, and the median survival time was 31.50 months, which was significantly better than that of the TP group, and the differences were statistically significant (all P values <0.05). Cox regression analysis showed that surgical methods, tumor differentiation degree, N staging and pathological types were independent risk factors for overall survival and cancer-specific survival. Conclusions:Surgical methods, tumor differentiation degree, N stage and pathological type were independent risk factors affecting the overall survival rate and cancer-related survival rate. The survival benefit of PD was significantly better than that of TP, and the clinical choice of TP treatment for patients with pancreatic head cancer should be cautious.