Objective To explore the protective effect of resveratrol (RSV) on intestine barrier injury induced by hemorrhagic shock and its mechanism in rats.Methods According to random number table method,sixty-four SPF grade male Sprague-Dawley (SD) rats were divided into four groups:Sham operation group (only the catheters were indwelled in arterial and venous passages after anesthesia),hemorrhagic shock model group (model group,the catheters were indwelled in arterial and venous passages after anesthesia,and 0.3 mL solvent was administrated after hemorrhagic shock),RSV group (the catheters were indwelled in arterial and venous passages after anesthesia,15 mg/kg RSV was administered after hemorrhagic shock),superoxide dismutase 2 (SOD2) specific inhibitor,2-Methoxyoestradiol (2-ME) group (on the basic treatment of RSV group,0.1 mmol/L 2-ME was administered).The hemorrhagic shock model was reproduced by femoral artery bleeding.After drug administration,all rats were divided into two parts.One part was used for observations on 24-hour survival rate and survival time,while in the other part,2 hours after the hemorrhagic shock,the blood was collected for determination of the content of serum D-lactic acid,and afterward the rats were executed to obtain small intestine tissues for the examination of histopathological changes and Chiu's score.Moreover,differences of expression levels of tight junction proteins (Occludin,Claudin,ZO-1) of small intestine tissue and the oxidative stress related indexes SOD2 activity and reduced glutathione (GSH),oxidized glutathione (GSSH),malonaldehyde (MDA) contents were compared among the groups.Results Compared with the sham group,the model group demonstrated decreased survival rate,SOD2 activity,GSH content,GSH/GSSH ratio,reduced survival time,significantly increased serum D-lactic acid activity,Chiu's score and MDA content,and decreased expressions of tight junction proteins in small intestine tissue.Compared with model group,the RSV group showed significant increased survival rate [75.0％ (6/8) vs.37.5％ (3/8)] and prolonged survival time (hours:21.0±4.3 vs.10.4±5.8,P ＜ 0.05),significantly decreased serum D-lactic acid (μg/L:380.18 ± 70.59 vs.500.88 ± 97.53) and Chiu's score (1.75 ± 0.71 vs.4.00± 0.53) in small intestine (both P ＜ 0.05),obviously increased expressions of tight junction proteins,SOD2 activity,GSH and GSH/GSSG [Occludin (gray value):0.89 ± 0.10 vs.0.43 ± 0.77,Claudin (gray value):0.78±0.06 vs.0.33 ± 0.05,ZO-1 (gray value):0.83 ± 0.06 vs.0.34 ± 0.07,all P ＜ 0.05],and the elevated SOD2 activity (kU/L:0.85 ± 0.12 vs.0.51 ± 0.11,P ＜ 0.05],as well as increased GSH content and GSH/GSSG ratio [GSH (μmol/L):7.25±1.01 vs.3.86±0.54,GSH/GSSG:6.39± 1.14 vs.1.56±0.25,both P ＜ 0.05] in the small intestine,and markedly reduced MDA content (ng/g:5.00± 1.31 vs.8.63±0.92,P ＜ 0.05).Compared with RSV group,the 2-ME group demonstrated significantly decreased survival rate [50.0％ (4/8) vs.75.0％ (6/8)] and further shorter survival time (hours:12.2 ± 5.7 vs.21.0±4.3),increased serum D-lactic acid (μg/L:463.88 ± 60.16 vs.380.18 ± 70.59),obviously elevated Chiu's score (3.13 ± 0.99 vs.1.75±0.71,P ＜ 0.05),decreased expressions of tight junction proteins [Occludin (gray value):0.55±0.04 vs.0.89±0.10,Claudin (gray value):0.38±0.05 vs.0.78±0.06,ZO-1 (gray value):0.41±0.04 vs.0.83±0.06,all P ＜ 0.05];moreover,the activity of SOD2,GSH content,GSH/GSSG ratio were greatly reduced [SOD2 activity (kU/L):0.58 ± 0.13 vs.0.85 ± 0.12,GSH (μmol/L):4.49 ± 0.52 vs.7.25 ± 1.01,GSH/GSSG:1.57 ± 0.39 vs.6.39 ± 1.14,all P ＜ 0.05],and increased MDA content (ng/g:6.25 ± 1.04 vs.5.00 ± 1.31,P ＜ 0.05).The small intestine tissue was basically normal in Sham group,and no significant pathological changes were seen;in the model group,the small intestine epithelial mierovilli were collapsed and the mucosal barrier was destroyed obviously;in the RSV group the damages of small intestine microvilli and barrier were markedly alleviated;in 2-ME group the pathological changes were more evident compared with those in the RSV group.Conclusion RSV can improve intestinal barrier injury following hemorrhagic shock in rats;its mechanism may be related to SOD2 activation.

Objective To determine if polydatin inhibited oxidative stress and inflammatory response in rats with sepsis-induced acute kidney injury (AKI).Methods Seventy-two rats (weighing 180-220 g) were randomly divided into the following groups: sham group, cecal ligation and puncture (CLP) CLP+normal saline group (group CN), group CLP+vehicle (group CV), and group CLP+polydatin (group CD) (n=18 each).Rats in groups CN, CV and CD underwent CLP to mimic sepsis-induced AKI.In sham group, the cecum was not ligated or punched, and the remaining procedures were the same as in group CLP.Normal saline, vehicle, and 30 mg/kg polydatin were administered at 6, 12, and 18 hours after CLP via the tail vein.At 24 hour post CLP, two clinically used markers of AKI, blood urea nitrogen (BUN), and creatinine (Cr) were tested, pathological changes of kidney tissue was observed under light microscopy in each group.Renal tubular damage assessment was carried out.Malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) content of renal tissue, serum cytokines such as TNF-α, IL-1β and IL-6, were also measured in each group at 24 hours after CLP.Results Compared with sham group, multiple indexes such as BUN, Cr, tubular injury scores, MDA content of renal tissue, and serum cytokines incluing TNF-α, IL-1β and IL-6 increased significantly (P<0.01), while SOD and GSH levels of renal tissue significantly decreased in groups CN and CV (P<0.01).Compared with groups CN and CV, the indicators such as BUN, Cr, tubular injury scores, MDA content of renal tissue, and serum cytokines such as IL-1β and IL-6 significantly decreased (P<0.05);while SOD and GSH levels of renal tissue significantly increased (P<0.05).Conclusion Sepsis caused by sepsis cecal ligation and puncture can cause acute kidney injury.Polydatin could alleviate kidney damage by attenuating systemic inflammatory response and inhibiting oxidative stress of renal tissue.

ObjectiveTo investigate the clinical value of fluorescence in situ hybridization (FISH) in the diagnosis of urothelial carcinoma.MethodsFrom September 2010 to October 2011,morning voiding urine of 27 patients with suspected urothelial carcinoma was collected for FISH examination.The results of FISH examination were compared with the results of pathological examination by endoscopic biopsy.Both sensitivity and specificity were compared respectively,and the cost of each kind of examination was also considered.ResultsOf 27 cases,pathological examination by endoscopic biopsy revealed 11 cases of urothelial carcinoma,FISH examination showed 9 cases of urothelial carcinoma,but only 7 cases in these 11 cases.The overall sensitivity of FISH examination was 63.6％ (7/11 ),the specificity was 87.5％(14/16).The cost per case of FISH examination (3100 yuan) was 3.1 times of pathological examination by endoscopic biopsy( 1000 yuan).ConclusionsIt showed that there is no advantage of FISH examination for diagnosis of urothelial carcinoma considering both the sensitivity and specificity,and the cost is also higher than that of pathological examination by endoscopic biopsy.It should be evaluated further when FISH examination is widely used in clinic.

A growing body of evidence suggests that p300 histone acetyltransferase plays important roles in cancer cell differentiation and proliferation. Here, we employed structure-based hierarchical virtual screening method to identify novel lead compounds of p300 histone acetyltransferase. From a screening library containing approximate 100 000 diverse druglike compounds, 33 compounds were chosen for experimental testing and one compound, 4-acetyl-2-methyl-N-morpholino-3,4-dihydro-2H-benzo[b][1, 4]thiazine-7-sulfonamide (17), showed as micromolar inhibitor. Based on its predicted binding pose, we investigated its binding characteristics by designing two series of structural modifications. The obtained structure-activity relationship results are consistent with the predicted binding model. We expect that the identified novel p300 histone acetyltransferase inhibitors will serve as starting points for further development of more potent and specific histone acetyltransferase inhibitors.

Objective To investigate the effects of drag-reducing polymers on microcirculation in 40%total body surface area burn-injured rats. Methods SD rats were randomized into control group, drag-reducing polymer (DRPs) group and normal saline (NS) group (5 minutes after scald, drag-reducing polymer or saline was injected for fluid resuscitation). Wet dry weigh ratio of lung, histopathologic changes and arterial blood gas at 24 hour were respectively measured by wet dry weigh ratio method, hematoxylin-eosin (HE) staining and arterial blood gas analysis. The velocity of flow of red cell in oblique ridge and the survival time of burn-injured rats were observed. Results Compared with control group, rats in NS group exhibit significant lung injury characterized by a high W/D (P < 0.01), accumulation of a large number of neutrophils in HE stain, low partial pressure of oxygen (PO2) and high lactate (Lac) (P<0.05 or P<0.01) in arterial blood. Compared with the NS group, DRPs treatment rats exhibit significantly reduced lung injury characterized by W/D reducing (P < 0.05), the reduction of neutrophil infiltration, increased PO2, decreased Lac (P<0.05, P<0.01). In addition, DRPs treatment obviously increases the burn-induced low velocity of flow of red cell in oblique ridge (P<0.01). Moreover, the survival time of burned rats can be improved by DRPs treatment (P < 0.05). Conclusion DRPs ameliorates burn-induced acute lung injury, the mechanism may be through improving the burn-induced microcirculation disorders.

Objective To investigate neutrophil lymphocyte ratio (NLR) in early-stage diabetic nephropathy and its clinic significance. Methods The 145 subjects were divided into two groups:the healthy control group (n=54) and early stage diabetic nephropathy group (n=91). The numbers of neutrophils (N) and lymphocytes (L) as well as the NLR values of peripheral blood and other biochemistry index were examined. Factors of early stage diabetic nephropathy were calculated us?ing variance and logistic regression analysis. Results Creatinine(Cr), total cholesterol(TC), triglyceride(TG), LDL-C, neu?trophils number and CRP in DN group were significantly higher than those of the control group and lymphocytes numbers of DN group were significantly lower than that of the control group (P<0.05 respectively);NLR values were significantly higher in diabetic nephropathy group compared with those of healthy control group(2.52±0.57 vs 1.82±0.60,t=6.997, P<0.01). Lo?gistic regression analysis showed that the risk factors of DN include NLR, TG and total cholesterol. NLR ( P <0.001, OR=8.951, OR 95%CI:3.595-22.287) was significantly associated with DN. Conclusion High NLR values may be a predic?tive and reliable marker ofearly-stage DN.

AIM:To investigate the change of short-chain acyl-CoA dehydrogenase (SCAD) expression during cardiomyocyte apoptosis and to explore the relationship between SCAD and cardiomyocyte apoptosis .METHODS: The neonatal rat cardiomyocytes treated by tert-butyl hydroperoxide (tBHP) were used as the model of cardiomyocyte apoptosis . The cell viability , the expression of SCAD at mRNA and protein levels , the activity of SCAD and the content of free fatty acids were determined .RESULTS:The mRNA and protein expression of SCAD decreased in the cardiomyocyte apoptosis model.Compared with negative control group , SCAD expression and activity were both significantly decreased in siRNA-1186 group, but the content of free fatty acids were obviously increased in the cardiomyocytes .Meanwhile, SCAD siRNA treatment triggered the same apoptosis as cardiomyocytes treated with tBHP .CONCLUSION: Down-regulation of SCAD may play an important role in primary cardiomyocyte apoptosis .Increase in the expression of SCAD may become an impor-tant part in intervening cardiomyocyte apoptosis .

OBJECTIVE:To establish a method of microbial limit test for liquid preparation of Iron sucrose injection before filtration and sterilization.METHODS:According to the microbial limit test in the 1005 and general rules 1006 of 2015 edition of Chinese Pharmacopoeia (vol.Ⅴ),plate method and membrane filtration method were used to measure total number of aerobic bacteria (Staphylococcus aureus,Pseudomonas aeruginosa,Bacillus subtilis,Candida albicans,Aspergillus niger) and total number of molds and yeasts (C.albicans,A.niger).The optimal test method was obtained by comparing the bacterial recoveries.RESULTS:By plate method,the recoveries of P aeruginosa and B.subtilis were 2％ and 5％.The test sample was diluted 10 times with pH 7.0 sodium chloride-peptone buffer solution,and the bacterial recoveries were in the range of 88％ to 96％;but he medium was dark in color.By membrane filtration method,without rinse solution,the bacterial recoveries in the range of 88％ to 95％.Add rinse solution,the bacterial recoveries were in the range of 91％ to 103％.After validated,the recoveries of menbrane filtration method with tlushing fluid ranged 50％-200 ％,which was in line with the requnements.CONCLUSIONS:The membrane filtration method established in this experiment has higher bacterial recovery rate than the plate method.The bacterial recoveries rate were higher after adding rinse solution,and no dark substance in the surface of filter membrane affect the accotmt.It can be used as the microbial limit test method for preparation liquid of Iron sucrose injection before filtration and sterilization.

ASCO-GU is one of the landmark meetings of urogenital cancer. Within 2022 meeting, the extended follow up result of adjuvant pembrolizumab after nephrectomy in renal cell carcinoma as well as the efficacy and safety of neoadjuvant Axitinib and avelumab for local advanced renal cell carcinoma have been released. There were also explorations in local therapy for oligometastasis, novel combination system therapy and regiments alterations. The further research protocol of immunostimulatory IL-2 cytokine prodrug and PARP inhibitor for metastatic RCC were also disclosed.

AIM:To investigate the effect of short-chain acyl-CoA dehydrogenase ( SCAD) on collagen expres-sion and proliferation of rat cardiac fibroblasts and to explore the relationship between SCAD and cardiac fibrosis . METHODS:The model of proliferation and collagen expression of rat cardiac fibroblasts induced by angiotensin II was es -tablished.After treatment with siRNA-1186, the expression of SCAD at mRNA and protein levels , fatty acids beta oxida-tion rate, ATP, the enzyme activity of SCAD and free fatty acids in the rat cardiac fibroblasts were determined . RESULTS:The mRNA and protein expression of SCAD was decreased in the rat cardiac fibroblasts induced by angiotensin II compared with the control cells , and the expression of collagen I and collagen III was significantly upregulated .Com-pared with negative control group , SCAD expression and activity , fatty acid beta-oxidation rate and ATP significantly de-creased in siRNA-1186 group, but the content of free fatty acids were obviously increased in the rat cardiac fibroblasts , and the expression of collagen I and collagen III was significantly up-regulated.CONCLUSION:The expression and synthesis disorder of collagen may be triggered by down-regulation of SCAD .SCAD may be a promising therapeutic target for myocar-dial fibrosis .