ABSTRACT
OBJECTIVE@#To investigate the effects of inhibiting Sonic Hedgehog (Shh) signaling on fibrous scar formation and functional outcome after ischemic brain injury.@*METHODS@#Adult SD rats were randomized into sham-operated group, middle cerebral artery occlusion (MCAO) and reperfusion (I/R) group, I/R with intraventricular empty adenoviral vector (rAd-NC) injection group, and I/R with adenovirus-mediated Shh knockdown (rAd-ShShh) group. After the treatments, the neurological deficits of the rats were assessed, and the protein and mRNA expressions of fibronectin (Fn), α-SMA, and Shh in the ischemic hemisphere were detected with immunofluorescence assay and qPCR; TUNEL staining was used for detecting neural cell apoptosis. In the cell experiment, primary meningeal fibroblasts isolated from neonatal SD rats were pretreated for 24 h with TGF-β1 or TGF-β1 plus cyclopamine (CYC) before oxygen-glucose deprivation for 150 min followed by reoxygenation for 72 h (OGD/R). CCK-8 assay and scratch test were performed to examine the changes in cell proliferation and migration, and immunofluorescence assay, qPCR and Western blotting were used for detecting cell transformation and the expressions of Shh, α-SMA, and Fn.@*RESULTS@#Cerebral I/R injury significantly increased the protein and mRNA expressions of Shh, α-SMA, and Fn in the ischemic hemisphere of the rats, but their expression levels were significantly lowered by intraventricular injection of rAd-Shshh (P < 0.05), which obviously increased cell apoptosis in the ischemic hemisphere (P < 0.05) and improved modified mNSS and modified Bederson scores of the rats (P < 0.05). In the cell experiment, pretreatment with TGF-β1 and TGF-β1+CYC both increased the viability of the primary meningeal fibroblasts after OGD/R. TGF-β1 significantly enhanced the migration ability and induced obvious transformation of the exposed cells (P < 0.05), but these effects were significantly attenuated by co-treatment with CYC (P < 0.05). The expressions of Shh, α-SMA and Fn in the TGF-β1 group were all significantly higher in TGF-β1-treated cells (P < 0.05) and were obviously lowered by co-treatment with CYC (P < 0.05).@*CONCLUSION@#Inhibition of Shh signaling may inhibit fibrous scar formation and functional recovery in rats after ischemic brain injury.
Subject(s)
Animals , Rats , Brain Injuries , Cicatrix , Hedgehog Proteins , RNA, Messenger , Rats, Sprague-Dawley , Transforming Growth Factor beta1ABSTRACT
OBJECTIVE@#To investigate the effect of TGF-β1 on Shh signaling pathway during the transformation of meningeal fibroblasts into myofibroblasts.@*METHODS@#Primary meningeal fibroblasts were isolated from neonatal (24 h) SD rats and purified using type Ⅳ collagenase. The isolated cells were treated with 10 ng/mL TGF-β1 alone or in combination with 20 μmol/L SB-431542 (a TGF-β1 receptor inhibitor) for 72 h, and the changes in proliferation and migration abilities of the fibroblasts were assessed with CCK-8 assay and cell scratch test. The expression of fibronectin (Fn) was detected with immunofluorescence assay, and Western blotting was performed to examine the expressions of Fn, α-SMA and Shh protein in the cells; the expression of Shh mRNA was detected with real-time fluorescence quantitative PCR.@*RESULTS@#TGF-β1 treatment obviously enhanced the proliferation and migration of primary meningeal fibroblasts (P < 0.05), and promoted the transformation of meningeal fibroblasts into myofibroblasts and the secretion of Fn (P < 0.05). TGF-β1 treatment also upregulated the expression of Shh at both protein and mRNA levels (P < 0.05). Treatment with SB-431542 partially blocked the effect of TGF-β1 on the transformation of meningeal fibroblasts (P < 0.05).@*CONCLUSION@#TGF-β1 can induce the transformation of meningeal fibroblasts into myofibroblasts by up-regulating Shh expression in Sonic Hedgehog signaling pathway.
Subject(s)
Animals , Rats , Fibroblasts/metabolism , Hedgehog Proteins , Myofibroblasts/metabolism , Rats, Sprague-Dawley , Transforming Growth Factor beta1/metabolismABSTRACT
OBJECTIVE@#To systematically evaluate the clinical efficacy of high-quality direct anterior approach (DAA) and other approaches for the treatment of elderly patients with femoral neck fracture.@*METHODS@#Literatures published in English or Chinese about the direct anterior approach and other approaches for hemiarthroplasty in femoral neck fracture were searched on Cochrane Library, PubMed, EMBASE, Web of science, Wanfang, CNKI databases from their establishment to May 2019. According to the inclusion and exclusion criteria, two researchers independently screened the literatures, and extracted the data. The quality of RCT were evaluated by Cochrane Risk of Bias Assessment Tool, and non-RCT were evaluated by the NOS scale. Meta-analysis was performed using the RevMan 5.3 software.@*RESULTS@#A total of 9 articles were included with 901 cases, in which 429 cases used DAA, and 472 used other approaches. DAA had a significantly lower dislocation rate compared to subgroup of posterior and posterolateral approach [=0.19, 95%CI (0.06, 0.61), =0.005]. No significant differences were found between DAA group and subgroup of direct lateral and anterolateral approach[=1.08, 95%CI(0.20, 5.76), =0.93]. Also there were no relevant differences between the DAA group and control in infection rate[=1.07, 95%CI(0.47, 2.43), =0.88], perioperative fracture rate[=0.95, 95%CI(0.36, 2.50), =0.92], re operation rate[=0.76, 95%CI(0.30, 1.89), =0.55], overall complication rate [=0.88, 95%CI (0.63, 1.22), =0.44], mortality [=1.33, 95%CI (0.84, 2.11), =0.23], operative time[MD=1.43, 95%CI(-5.85, 8.71), =0.70].@*CONCLUSION@#The current evidenceindicates that the DAA was associated with a significantly lower dislocation rate compared to posterior capsular approaches for hemiarthroplasty. There was no significant difference in dislocation rate with the lateral and anterolateral approach.
Subject(s)
Aged , Humans , Antiviral Agents , Arthroplasty, Replacement, Hip , Femoral Neck Fractures , General Surgery , Hemiarthroplasty , Hepatitis C, Chronic , Reoperation , Treatment OutcomeABSTRACT
The dried roots of Berberis heteropoda Schrenk have traditionally been used to treat acute gastroenteritis and dysentery. The aim of this study was to confirm the antibacterial activity of an extract of Berberis heteropoda Schrenk rootin vitro and its therapeutic effects on rats with diarrhea-predominant irritable bowel syndrome (D-IBS) in vivo, as well as to identify the related signaling pathways. A water extract of Berberis heteropoda Schrenk root (BHS) inhibited the growth of S. aureus, E. coli, P. aeruginosa and S. faecalis. BHS potentially damaged the structure of the bacterial cell membrane and decreased the activity of some membranous enzymes, eventually killing the S. aureus, E. coli, P. aeruginosa and S. faecalis bacteria. Oral administration of BHS (low, middle and high dose group, L, M and H) significantly alleviated the abdominal pain, diarrhea, and depression-like symptoms of D-IBS rats, and the efficacy index ranged from 30% to 60%, indicating that the BHS treatment was effective. BHS (L, M and H) alleviated the abnormal pathological changes in the brain, as evidenced by HE staining. The expression of CHAT, 5-HT, C-FOS and CGRP was reduced by the BHS treatment (L, M and H). Our findings provide novel insights into the use of the natural product BHS to inhibit pathogenic bacteria by destroying the bacterial structure, indicating that BHS possesses certain biological activities. Furthermore, BHS has the potential to alleviate diarrhea, abdominal pain and depression-like behaviors in D-IBS rats by regulating the brain-gut peptide levels.
ABSTRACT
Objective To analyze the factors correlated with perinatal death so as to provide the basis for reducing the perinatal mortality.Methods A respective study was conducted with analysis of perinatal mortality monitoring data,birth defects data and the health status report of non-registered pregnant women from 2012 to 2016 in Taizhou. We compared the differences in the indexes of perinatal mortality,birth defects rate and the proportion of elderly pregnant women in different years,domicile place and regions.Results The perinatal mortality rate was 6.80‰,decreasing annually from 2012 to 2016 (P<0.01). The average perinatal mortality rate of floating population was 9.28‰,which is higher than the 5.64‰ rate of local population (P<0.01). The proportion of elderly pregnant women was 10.30%,showing an upward trend (P<0.01) and the perinatal mortality of elderly pregnant women was 10.60‰,significantly higher than the total mortality (P<0.01). The leading cause of perinatal death was birth defect and the defect rate of perinatal birth was 35.86‰,showing an upward trend (P<0.01) while the average mortality rate of birth defects was decreasing (P<0.01). There were statistically significant differences(P<0.01) in perinatal mortality,birth defects,sex ratio and proportion of elderly pregnant women in different regions of Taizhou. Compared with the perinatal in local population,mother age,education background,maternal times and register time of pregnant women of the perinatal in floating population was significantly different (P<0.01). Conclusion The perinatal mortality in Taizhou declined year by year. Elderly pregnant age,birth defects,and floating population are the main positive factors of perinatal mortality.
ABSTRACT
The study was designed to explore the effects of HS060098 on activation of peroxisome proliferator-activated receptors (PPARα, γ and δ) and in the down-regulation of hyperlipidemia in golden hamster. Luciferase gene reporters of PPARα, PPARγ and PPARδ were constructed in HepG2 cells and the green fluorescent protein (GFP) was used as an internal reference. Transfected cells were then cultured with various concentrations of HS060098 for 24 h. The peroxisome proliferator-response element luciferase activity was determined by the dual-luciferase reporter gene assay system. To investigate the lipid-lowering effect of HS060098, hyperlipidemic golden hamsters fed by high-diet were administered orally with HS060098 through prophylactic and therapeutic approaches respectively. The levels of blood lipids such as total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and fat index in hamsters were evaluated. The results showed that HS060098 was a potent activator of PPAR δ with a good selectivity and the median effective concentration (EC 50) is 0.01 μmol·L-1, while no obvious PPARα and PPARγ activation was observed. In the golden hamster, oral administration of HS060098 (5, 10, 20 mg·kg-1·d-1) for 2 weeks, led to a significant decrease the concentrations of plasma TC, TG, LDL-C and fat index (PPPPδ agonist with a significant activity in the prevention and therapy of hyperlipemia in golden hamster.
ABSTRACT
<p><b>OBJECTIVE</b>To observe the effects of comprehensive therapy (CT) with electroacupuncture (EA) in combination with psycho-intervention (PI) on the cognitive function and event-related potentials (ERP), P300 and mismatch negativity (MMN), in patients with internet addiction (IA) for a preliminary exploration of the possible mechanism of the therapy.</p><p><b>METHODS</b>One hundred and twenty patients with IA were randomly divided into three groups, and a total of 112 subjects reached the final analysis of the trial, the EA group (39 patients), the PI group (36 patients) and the CT group (37 patients). EA was applied at acupoints Baihui (GV20), Sishencong (EX-HN1), Hegu (LI4), Neiguan (PC6), Taichong (LR3) and Sanyinjiao (SP6), once every other day; PI with the cognitionbehavior mode was implemented every 4 days; both EA and PI were used in the CT group. The treatment course for all patients was 40 days. Changes before and after treatment in terms of scoring by the IA self-rating scale, short-term memory capacity, short-term memory span, and the latency and amplitude of P300 and MMN in patients were observed.</p><p><b>RESULTS</b>After treatment, in all groups, the IA score was lowered significantly (P <0.05) and scores of short-term memory capacity and short-term memory span increased significantly (P <0.05), while the decreased IA score in the CT group was more significant than that in the other two groups (P <0.05). ERP measurements showed that P300 latency was depressed and its amplitude raised in the EA group; MMN amplitude increased in the CT group (all P<0.05).</p><p><b>CONCLUSION</b>The EA in combination with PI could improve the cognitive function of IA patients, and its mechanism might be related to the speedup of cerebral discrimination on external stimulus and the enhancement of effective resource mobilization during information processing of the brain.</p>
Subject(s)
Female , Humans , Male , Young Adult , Behavior, Addictive , Psychology , Therapeutics , Cognition , Physiology , Combined Modality Therapy , Electroacupuncture , Methods , Event-Related Potentials, P300 , Physiology , Internet , Latency Period, Psychological , Memory, Short-Term , Physiology , Patient DropoutsABSTRACT
Objective: To investigate the influence of Taxus polysaccharide on myocardial NADPH oxidase mRNA, SOD, and MDA in myocardial ischemia-reperfusion injury (MIRI) model of Beagle's dogs. Methods: Beagle's dogs (30) were randomly divided into Sham operation, model, low-dose Taxol polysaccharide, high-dose Taxol polysaccharide, and Carvedilol groups, six in each group, and MIRI model was established after 7 d administration. Stained with HE, pathological changes in myocardial tissue were observed with light microscopy; NADPH oxidase p47phox (NCF-47K) mRNA expression was detected with in situ hybridization; Myocardial SOD and MDA contents were detected with colorimetry. Results: Under light microscope, serious cardiac cells disorders, fracture, karyopyknosis, and significant eosinophilic cytoplasm existed, mild to moderate hyperemia and edema and inflammatory cell infiltration appeared in the model group. However, in the high-dose group, myocardial cells disorders and destruction existed in a lesser extent, karyopyknosis and eosinophilic cytoplasm decreased significantly, and some organizations were still mild hyperemia and edem. Myocardial NCF-47K mRNA expression of Beagle's dogs in the model group and low-dose group were significantly higher than that in the Sham-operated group (P<0.01), NCF-47K mRNA expression of Beagle's dogs in the high-dose group was significantly lower than that in the model group (P<0.05). And SOD content in myocardial tissue of the model group and the treatment group was significantly lower than that in the Sham-operated group (F<0.01). SOD content in the high dose group was significantly higher than that in the model group (P<0.01). MDA contents in myocardial tissue in the model and low-dose groups were significantly higher than those in the Sham-operated group (P<0.05). MDA content in high-dose group was significantly lower than that in the model group (P<0.05). Conclusion The Taxus polysaccharide may reduce ischemia-reperfusion myocardial injury by reducing the expression of NADPH oxidase, increasing SOD activity, and reducing injury of O2.- and other oxygen free radicals in myocardial cell.
ABSTRACT
Objective To explore the clinical effect of modified frontalis muscle suspension for severe blepharoptosis correction. Design Retrospective case series. Participants Fifty-six cases (101 eyes) with severe blepharoptosis. Methods Modified frontalis mus- cle suspension was adopted. The technique included single blepharoplasty-type incision, dissecting the posterior gaps of frontalis muscu- lar fasciae ahead,then euthyphoria isolating anterior gaps of rontalis muscular fasciae, using frontalis muscle transfer without vertical incision. Main Outcome Measure The positon chang of the upper eyelid in the primary position gaze. Results The follow-up period ranged from 8 to 20 months (mean, 13.6 months). All the patients were deemed to have a good surgical outcome. Complications such as ectropion and corneal exposure were avoided. But ten eyes required reoperation for undercorrection, six eyes for overcorrection and two eyes for entropion. Conclusion This surgical technique is a useful procedure that results in substantial cosmetic and functional im- provement with few complications.
ABSTRACT
<p><b>OBJECTIVE</b>To observe the preventive effect of Radix Paeoniae Rubra (RPR) to restenosis after carotid balloon injury in rabbits.</p><p><b>METHODS</b>The rabbit model of carotid balloon injury was established adopting Clowes method, and treated with extract of RPR. Component of new genesic intima and expression of proliferating cell nuclear antigen (PCNA) and macrophage was determined by immunochemical stain. The collagen of type I was detected by special staining for blood vessels and the area of new genesic intima was measured by image assay system.</p><p><b>RESULTS</b>RPR could remarkably decreased the PCNA positive expression and inhibit the proliferation of collagen type I and reduce the generating of new intima.</p><p><b>CONCLUSION</b>RPR has significant preventive effect on the restenosis after carotid ballon injury in high fat-diet induced atherosclerotic rabbits.</p>