Pirfenidone alleviates urethral stricture following urethral injury in rats by suppressing TGF-β1 signaling and inflammatory response / 南方医科大学学报

OBJECTIVE@#To investigate the effect of pirfenidone for reducing urethral stricture following urethral injury in rats and explore the possible mechanism.@*METHODS@#Thirty male SD rats were randomly assigned into negative control group, positive control group and pirfenidone group (n=10). In pirfenidone and positive control groups, the rats were subjected to incision of the posterior urethral cavernous body followed by daily intraperitoneal injection of pirfenidone (100 mg/kg) and an equivalent volume of solvent, respectively. The rats in the negative control group were given intraperitoneal injections of solvent without urethral injury. At two weeks after modeling, retrograde urethrography was performed for observing urethral stricture, and the injured urethral tissues were harvested for HE staining, Masson staining, immunohistochemical staining and Western blotting for detecting the protein expressions of α-SMA and TGF-β1. The mRNA expressions of the inflammatory factors TNF-α, IL-6, and IL-1β were detected using qRT-PCR.@*RESULTS@#The body weight of the rats in pirfenidone group was significantly decreased compared with that in the other two groups (P < 0.05). Retrograde urethrography showed significant narrowing of the urethra in the positive control group but not in the pirfenidone group. HE staining of the injured urethral tissues showed obvious proliferation of urethral epithelial cells with narrow urethral cavity and increased inflammatory cells in positive control group. The pathological findings of the urethra were similar between pirfenidone group and the negative control group. Masson staining revealed obviously reduced collagen fibers and regular arrangement of the fibers in pirfenidone group as compared to the positive control group. Compared with those in the negative control group, the expressions of α-SMA and TGF-β1 were significantly increased in the positive control group, and pirfenidone treatment significantly inhibited their expressions (P < 0.05 or 0.01). Pirfenidone also significantly inhibited the mRNA expressions of TNF-α, IL-6, and IL-1β in the injured urethral tissue (P < 0.05 or 0.01).@*CONCLUSION@#Pirfenidone can prevent urethral fibrosis and stricture after urethral injury possibly by inhibiting the TGF-β1 pathway and inflammatory response.

The association of blue light-induced human retinal pigment epithelium cell damage with intercellular free Ca2+ change in vitro / 中华实验眼科杂志

Background Investigating the association of blue light-induced damage of retinal pigmenepithelial (RPE) cellwith intracellulaCa2+ conteniimportanfounderstanding the mechanism of retinal disorders.Objective Thistudy wato establish blue light-induced damage model of human RPE celland explore the relationship between the damage of RPE cell and intracellulaCa2+ content.MethodHuman RPE cellwere cultured and passaged.Cell vitality waassayed by trypan blue staining.Fourth-generation cellwere used in these experiments.The cellwere exposed to blue lighwith an intensity of (2000±500)lx fo3,6,9 o12 hours,and the rate of apoptosiwaassayed by TUNEL to assesthe optimal irradiation time focellcultured.The cellwere then randomized into the withouirradiation group,irradiation only group,nifedipine group,ligh+ nifedipine group,(-) BayK8644 group and ligh+ (-) BayK8644 group.The laseconfocal microscope waused to determine the fluorescence intensity of intracellulafree Ca2+ aan excitation wavelength of 488 nm and an emission wavelength of 505 nm.The cell imagewere analyzed using computesoftware.The differenceof fluorescence intensity among the differengroupwere compared by one-way analysiof variance.ResultTrypan blue staining showed thathe viability of RPE cellwamore than 90％ afteculturing and passaging.No apoptoticell waseen aftelighexposure fo3 hours.However,differennumberof apoptoticellappeared aftelighexposure fo6,9 and 12 hours.The fluorescence intensity of intracellulafree Ca2+ in the nifedipine group wasignificantly lowethan thaof the withouirradiation group othe ligh+ nifedipine group(both aP=0.000).Lasescanning confocal microscopy showed thathe fluorescence intensitieof intracellulafree Ca2+ in the irradiation only group,(-) BayK8644 group,ligh+ (-)BayK8644 group were highethan thaof the withouirradiation group,with statistical significancebetween them(all P=0.000).No significandifferencewere found in the fluorescence intensity of intracellulafree Ca2+ between the ligh+ nifedipine group and withouirradiation group awell abetween the (-)BayK8644 group and the ligh+(-) BayK8644 group(P =0.339,P =0.410).ConclusionThe optical conditionfoblue light-induced RPE cell damage were exposure of blue-ligha(2000± 500) lx fo6 hourand culturing the cellfo24 hours.Blue lighexposure can induce damage of human RPE cellprobably by triggering the increase of intracellulafree Ca2+ concentration.

Multi-center clinical trial of FLAMIGEL (hydrogel dressing) for the treatment of residual burn wound / 中华烧伤杂志

<p><b>OBJECTIVE</b>To evaluate the effect of FLAMIGEL (hydrogel dressing) on the repair of residual burn wound.</p><p><b>METHODS</b>Sixty burn patients with residual wounds hospitalized in 6 burn units from November 2011 to May 2012 were enrolled in the multi-center, randomized, and self-control clinical trial. Two residual wounds of each patient were divided into groups T (treated with FLAMIGEL) and C (treated with iodophor gauze) according to the random number table. On post treatment day (PTD) 7 and 14, wound healing rate was calculated, with the number of completely healed wound counted. The degree of pain patient felt during dressing change was evaluated using the visual analogue scale (VAS). The mean numbers of wounds with score equal to zero, more than zero and less than or equal to 3, more than 3 and less than or equal to 6, more than 6 and less than or equal to 10 were recorded respectively. Wound secretion or exudate samples were collected for bacterial culture, and the side effect was observed. Data were processed with repeated measure analysis of variance, t test, chi-square test, and nonparametric rank sum test.</p><p><b>RESULTS</b>Wound healing rate of groups T, C on PTD 7 was respectively (67 ± 24)%, (45 ± 25)%, and it was respectively (92 ± 16)%, (72 ± 23)% on PTD 14. There was statistically significant difference in wound healing rate on PTD 7, 14 between group T and group C (F = 32.388, P < 0.01). Ten wounds in group T and four wounds in group C were healed completely on PTD 7, with no significant difference between them (χ(2) = 0, P > 0.05). Forty-two wounds in group T and seven wounds in group C healed completely on PTD 14, with statistically significant difference between them (χ(2) = 42.254, P < 0.01). Patients in group T felt mild pain during dressing change for 37 wounds, with VAS score higher than zero and lower than or equal to 3. Evident pain was observed in patients of group C during dressing change for 43 wounds, and it scored higher than 3 and less than or equal to 6 by VAS evaluation. There was statistically significant difference in mean number of wounds with different grade of VAS score between group T and group C (Z = -4.638, P < 0.01). Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, E. coli, Baumanii, and Staphylococcus epidermidis were all detected in both groups, but there was no statistical difference between group T and group C (χ(2) = 0.051, P > 0.05). No side effect was observed in either of the two groups during the whole trial.</p><p><b>CONCLUSIONS</b>FLAMIGEL can accelerate the healing of residual burn wounds and obviously relieve painful sensation during dressing change.</p>

Association between both resistin, visfatin and insulin resistance as well as β cell function in the first-degree relatives of type 2 diabetes mellitus / 中华流行病学杂志

Objective To study the association between the levels of scrum resistin, visfatin and insulin resistance as well as β-cell dysfunction in the first-degree relatives (FDR) of type 2 diabetes mellitus (T2DM), and to investigate the role of these adipocytokins in pathogenesis of T2DM. Methods Serum levels of resistin, visfatin as well as fasting true insulin (FTI), proinsulin (FPI) levels were measured in 71 patients with newly diagnosed T2DM. 55 subjects with IGT/IFG and 174 NGT from first-degree relatives of T2DM, and 114 subjects of NGT without T2DM family history served as control group (NC). Insulin resistance was assessed by the homeostasis model assessment (HOMA-IR) and β-cell function was evaluated by HOMA-β and fasting PI-to-TI ratio (FPI/TI). Lipid profile, liver function and kidney function were also tested. Anthropometrical parameters such as body mass index (BMI), waist circmference and blood pressure were also recorded and life style and food intake spectrum investigated. Results (1)There were no significant differences of serum resistin levels among the four groups (P ＞ 0.05 ). The serum resistin level was not correlated with HomA-IR, HomA-β and obesity markers (P＞0.05). (2) The serum visfatin levels of DM group, IGT/IFG and NGT group were lower than the NC group (P＜0.05). There were no significant difference among DM group, IGT/IFG group and NGT. The serum visfatin level was not correlated with HOMA-IR and obesity markers (P＞0.05) , but negatively correlated with fasting blood glucose, 2 h postprandial blood glucose and blood pressure (P＜0.05). Conclusion The adipokine profile in FDRs of T2DM had distinctively altered before the development of impaired glucose tolerance. Serum levels of visfatin, showed a favorable effect on glucose metabolism also had a significant decrease on serum levels in the early stage of T2DM.