Objective:To evaluate the effect of emodin on liver injury in a mouse model of intestinal ischemia-reperfusion (I/R) and the role of heme oxygenase-1-mediated autophagy.Methods:Twenty-four SPF-grade healthy male C57BL/6 mice, aged 6-8 weeks, weighing 18-22 g, were divided into 4 groups ( n=6 each) using a random number table method: sham operation group (Sham group), I/R group, emodin group (E group) and emodin plus HO-1 inhibitor Zinc Protoporphyrin Ⅸ (ZnPP) group (ES group). The intestinal I/R injury model was established by clamping the superior mesenteric artery for 45 min followed by 120 min of reperfusion. Emodin 40 mg/kg dissolved in 5% methylcellulose sodium was given by gastric gavage once a day for 5 days before ischemia in E group. Emodin 40 mg/kg dissolved in 5% methylcellulose sodium was given by gastric gavage once a day for 5 days before intestinal I/R, and ZnPP 7.5 mg/kg was injected via the tail vein at 12 h before ischemia in ES group. Orbital venous blood samples were collected at the end of reperfusion for determination of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations. Then the mice were sacrificed, and liver tissues were obtained for microscopic examination of the pathological changes (after HE staining) and for determination of the activity of superoxide dismutase (SOD), content of malondialdehyde (MDA), expression of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) mRNA (by fluorescent quantitative polymerase chain reaction), the expression of HO-1, autophagy-related protein Beclin1 and microtubule-associated protein 1 light chain 3 (LC3) (by Western blot). The LC3-Ⅱ/Ⅰ ratio was calculated. Results:Compared with Sham group, the activity of SOD was significantly decreased, the content of MDA and serum ALT and AST concentrations were increased, the expression of IL-6 and TNF-α mRNA and HO-1 was up-regulated, the expression of Beclin1 was down-regulated, the LC3-Ⅱ/Ⅰ ratio was decreased ( P<0.05), and the pathological changes of liver tissues were found in I/R group. Compared with I/R group, the activity of SOD was significantly increased, the content of MDA and serum ALT and AST concentrations were decreased, the expression of IL-6 and TNF-α mRNA was down-regulated, the expression of HO-1 and Beclin1 was up-regulated, the LC3-Ⅱ/Ⅰ ratio was increased ( P<0.05), and the pathological changes of liver tissues were significantly attenuated in E group ( P<0.05). Compared with E group, the activity of SOD was significantly decreased, the content of MDA and serum ALT and AST concentrations were increased, the expression of IL-6 and TNF-α mRNA was up-regulated, the expression of HO-1 and Beclin1 was down-regulated, the LC3-Ⅱ/Ⅰ ratio was decreased ( P<0.05), and the pathological changes of liver tissues were aggravated in ES group. Conclusions:Emodin can alleviate liver injury induced by intestinal I/R in mice, and the mechanism may be related to the activation of HO-1-mediated autophagy.

Objective:To evaluate the effect of artesunate on intestinal ischemia/reperfusion (I/R)-induced lung injury in mice and relationship with heme oxygenase-1 (HO-1).Methods:Twenty-four healthy SPF male C57BL/6 mice, aged 8-9 weeks, weighing 18-22 g, were divided into 4 groups ( n=6 each) using a random number table method: sham operation group (group Sham), intestinal I/R group (group I/R), artesunate group (group A), and artesunate plus HO-1 inhibitor Zinc protoporphyrin Ⅸ(ZnPP) group (group AS). The model of intestinal I/R injury was established by occluding the superior mesenteric artery for 45 min followed by 2 h reperfusion in anesthetized animals.Artesunate 40 mg/kg was injected via the tail vein at 1 h before ischemia in group A. ZnPP 7.5 mg/kg was injected via the tail vein at 12 h before ischemia, and artesunate 40 mg/kg was injected via the tail vein at 1 h before ischemia in group AS.The animals were sacrificed at the end of reperfusion, and the lung tissues were obtained for microscopic examination of the pathologic changes and for determination of the wet/dry lung weight (W/D) ratio, myeloperoxidase (MPO) activity, malondialdehyde (MDA) content, expression of interleukin-6 (IL-6) mRNA (by fluorescence quantitative polymerase chain reaction) and apoptotic index (AI) (by TUNEL). The lung injury score was assessed. Results:Compared with group Sham, the lung injury score, W/D ratio, MPO activity, MDA content and AI were significantly increased, and the expression of IL-6 mRNA was up-regulated in group I/R ( P<0.05). Compared with group I/R, the lung injury score, W/D ratio, MPO activity, MDA content and AI were significantly decreased, and the expression of IL-6 mRNA was down-regulated in group A ( P<0.05). Compared with group A, the lung injury score, W/D ratio, MPO activity, MDA content and AI were significantly increased, and the expression of IL-6 mRNA was up-regulated in group AS ( P<0.05). Conclusions:Artesunate can alleviate intestinal I/R-induced lung injury, and the mechanism may be related to activation of HO-1 in mice.

Objective:To explore the predictive value of the systemic immune inflammation index (SII) for the risk of bone metastases in patients with newly diagnosed prostate cancer (PCa).Methods:From Jun. 2012 to Jul. 2019, the clinical features of 308 patients were retrospectively analyzed. For the baseline clinical data of the patients with newly diagnosed PCa, the median age was 71(65-76) years, there were 59(19.2%) patients with a positive digital rectal examination (DRE). In addition, the median serum total prostate-specific antigen (tPSA), prostate volume (PV) and prostate-specific antigen density(PSAD)were 60.55(23.55-100.00) ng/ml, 39.35(28.29-56.66)ml and 1.27(0.58-2.52)ng/(ml·cm 3), respectively. There were 33(10.7%)patients with prostate biopsy Gleason score≤6, 115(37.3%)patients with a Gleason score=7 and 160(52.0%)patients with a Gleason score≥8. The T clinical stage also obtained, including 21(6.8%)diagnosed as T 1 stage, 87(28.2%)T 2 stage, 65(21.1%)T 3stage, 135(43.9%)T 4 stage. SII was calculated by the formula platelet×neutrophil/lymphocyte, and the median(interquartile range)of SII was 458.60(300.42-727.11)/L. According to the results of bone scanning, the patients were divided into bone metastasis(146, 47.4%)and a non-bone metastasis groups(162, 52.6%). The differences in the baseline clinical characteristics between the two groups were analyzed. The risk factors of bone metastasis were analyzed by univariate and multivariate logistic regression analysis. The diagnostic efficiency of the risk factors were evaluated by receiver operating characteristic(ROC)curve. Results:The median(interquartile range)of SII was 564.78/L(333.85-961.93/L)in patients with bone metastasis which were higher than those without bone metastasis 413.01(267.63-601.79)/L( P<0.001). The median(interquartile range)of tPSA were 97.79(48.20-119.10)ng/ml in bone metastasis group and 32.56(17.89-72.70)ng/ml in non-bone metastasis group ( P<0.001). The median(interquartile range)of PSAD were 1.91(0.97-3.55)ng/(ml·cm 3)and 0.90(0.45-1.77)ng/(ml·cm 3)in these two groups( P<0.001), respectively. In bone metastasis group, there were 132(90.4%)patients with a positive DRE, yet there were only 117(72.2%) patients with a positive DRE in the other group ( P<0.001). There were 7(4.8%)patients with prostate biopsy Gleason score≤6, 50(34.2%)patients with a Gleason score=7 and 89(61.0%)patients with a Gleason score≥8 in bone metastasis group. There were 26(16.1%)patients with prostate biopsy Gleason score≤6, 65(40.1%)patients with a Gleason score=7 and 71(43.8%)patients with a Gleason score≥8 in non-bone metastasis group ( P<0.001). There were statistically significant difference between the two groups in T clinical stage( P<0.001). In bone metastasis group, there were 2(1.4%)T 1 stage, and 19(13.0%)T 2 stage, 25(17.1%)T 3stage, and 100(68.5%)T 4 stage. Comparatively, there were 19(11.7%)T 1 stage, 68(42.0%)T 2 stage, 40(24.7%)T 3stage, and 35(21.6%)T 4 stage in the other group. There were no statistically significant difference between the two groups in term of age( P=0.057) and TPV( P=0.222). Univariate and multivariate logistic regression analysis showed that tPSA( P=0.003), SII( P<0.001), T clinical stage( P<0.001)could be regarded as independent risk factors of bone metastasis of PCa. Area under the curve of SII+ tPSA was 0.770, which was higher than SII(0.653)or tPSA(0.729) alone( P<0.05). When the cut-off value was 727.72/L, the sensitivity and specificity of the diagnosis of SII alone were 38.4% and 87.7%. The sensitivity and specificity of tPSA alone were 67.1%and 75.9% when the cut-off value was 73.02ng/ml. The sensitivity was 72.6% and the specificity was 71.6% when SII and tPSA was combined. Conclusions:SII is an independent predictor of bone metastasis of newly diagnosed with PCa. , and the patients were at high risk when SII exceeded 727.72/L. The combination of SII and tPSA can improve its predictive validity for the risk of bone metastasis.

Objective:To evaluate the role of cannabinoid type 2 receptor (CB2R) in sevoflurane postconditioning-induced reduction of intestinal ischemia-reperfusion (I/R) injury in rats.Methods:Twenty-four clean-grade healthy male Sprague-Dawley rats, aged 8-10 weeks, weighing 220-270 g, were divided into 4 groups ( n=6 each) using a random number table method: sham operation group (group Sham), intestinal I/R group (group I/R), intestinal I/R+ sevoflurane postconditioning group (group Sevo) and intestinal I/R+ sevoflurane postconditioning+ CB2R antagonist AM630 group (group AM). The model of intestinal I/R injury was established by occluding the superior mesenteric artery for 45 min followed by 2 h reperfusion.In the group Sevo, 2% sevoflurane was inhaled immediately at the beginning of reperfusion for 30 min.In the group AM, CB2R antagonist AM630 3 mg/kg was intraperitoneally injected at 1 h before ischemia, and the other treatments were similar to those previously described in group Sevo.At 2 h of reperfusion, the animals were sacrificed after anesthesia, and small intestinal tissues were obtained for microscopic examination of the pathologic changes which was scored according to Chiu and for determination of wet/dry weight ratio (W/D ratio), for detection of malondialdehyde (MDA) content (by thiobarbituric acid colorimetry), for determination of myeloperoxidase (MPO) activity (by MPO assay) and cleaved caspase-3 protein expression (by Western blot). Results:Compared with group Sham, the Chui score, W/D ratio, MDA content and MPO activity in the intestinal tissues were significantly increased, cleaved caspase-3 expression was up-regulated in group I/R ( P<0.05). Compared with group I/R, the Chui score, W/D ratio, MDA content and MPO activity in the intestinal tissues were significantly decreased, cleaved caspase-3 expression was down-regulated in group Sevo ( P<0.05). Compared with group Sevo, the Chui score, W/D ratio, MDA content and MPO activity were significantly increased, cleaved caspase-3 expression was up-regulated in group AM ( P<0.05). Conclusion:CB2R is involved in the process of sevoflurane postconditioning-induced reduction of intestinal I/R injury in rats.

Squamous cell carcinoma (SCC) of the renal pelvis is extremely rare and hardly to be diagnosed due to its lack of specificity in clinical manifestations and traditional imaging features. We reported a case with history of multiple operations for double kidney stones, who was admitted to our hospital twice due to "right kidney ureteral stones, left kidney complex stones, chronic renal insufficiency and urinary tract infection" . During this period, a total of 6 surgeries were performed. In the first 19-day hospitalization, right transurethral ureteroscopic lithotripsy and right percutaneous nephroscope lithotripsy(PCNL)were performed respectively. And 20 days later, the patient was admitted to hospital again for management of left complex kidney stones, and the left side PCNL was performed for 4 times within 27 days. During the two hospitalizations, no tumor was reported during the three times of contrast-enhanced CT examination of the urinary system. The patient continued to have fever after the 4th time of left PCNL, with failure of anti-infection treatment. Then, the of the left renal pelvis was considered clinically, and left nephrectomy was suggested after communication with the patient and his family members. Postoperative pathology confirmed renal pelvis SCC. After surgery, the patient’s temperature was back to normal and then discharged. The patient died 3 months after discharging due to the systemic metastasis.

Objective To evaluate the role of phosphatidylinositol 3-kinase ( PI3K)∕protein kinase B ( Akt) signaling pathway in propofol-induced reduction of intestinal ischemia-reperfusion ( I∕R) injury in rats. Methods Thirty-two healthy male Sprague-Dawley rats, aged 2-3 months, weighing 225-275 g, were divided into 4 groups ( n=8 each) using a random number table method: sham operation group ( Sham group), intestinal I∕R group ( I∕R group), propofol group ( P group), and PI3K inhibitor wortmannin plus propofol group ( W+P group) . Intestinal ischemia was induced by occluding the superior mesenteric ar-tery for 45 min followed by 2 h of reperfusion to establish the model of intestinal I∕R injury. Propofol was in-travenously infused at a rate of 20 mg·kg-1 ·h-1 starting from the onset of reperfusion until the end of reper-fusion in group P. Wortmannin 15 μg∕kg was intravenously injected at 25 min before reperfusion, and propofol was intravenously infused at a rate of 20 mg·kg-1 ·h-1 starting from the onset of reperfusion until the end of reperfusion in group W+P. Rats were sacrificed at 2 h of reperfusion, and small intestinal tissues were obtained for microscopic examination of pathologic changes of intestinal mucosa and for determination of wet∕dry weight ratio (W∕D ratio), malondialdehyde (MDA) content (by thiobarbituric acid colorimetric method) , superoxide dismutase ( SOD ) activity ( using xanthine oxidase method ) , myeloperoxidase ( MPO) activity ( by MPO assay) , and phosphorylated Akt ( p-Akt) expression ( by Western blot) . Intes-tinal damage was assessed and scored according to Chiu. Results Compared with group Sham, Chiu' s score, W∕D ratio, MDA content and MPO activity were significantly increased, the SOD activity was de-creased, and p-Akt expression was down-regulated in group I∕R (P<0. 05). Compared with group I∕R, Chiu's score, W∕D ratio, MDA content and MPO activity were significantly decreased, the SOD activity was increased, and p-Akt expression was up-regulated in group P (P<0. 05). Compared with group P, Chiu's score, W∕D ratio, MDA content and MPO activity were significantly increased, the SOD activity was decreased, and p-Akt expression was down-regulated in group W+P (P<0. 05). Conclusion The mechanism by which propofol reduces intestrnal I∕R injury is related to activating PI3K∕Akt signaling path-way and inhibiting inflammatory and oxidative stress responses in rats.

Objective To evaluate the effect of heme oxygenase-1 (HO-1) protein transduction on acute lung injury in septic rats.Methods Eighteen healthy male Sprague-Dawley rats,aged 7-9 weeks,weighing 210-260 g,were randomly allocated into 3 groups (n =6 each) using a random number table:sham operation group (group Sham),sepsis group (group Sep),and fusion protein PEP-1-HO-1 group (group HO).Sepsis was produced by cecal ligation and puncture (CLP).In group HO,PEP-1-HO-1 fusion protein 0.6 mg was injected via the left iliac vein at 1 h before CLP and 5 h after CLP.The equal volume of normal saline was given instead of PEP-1-HO-1 in Sham and Sep groups.At 12 h after CLP,blood samples were collected from the right common carotid artery for measurement of serum tumor necrosis factoralpha (TNF-α) and interleukin-6 (IL-6) concentrations.The rats were then sacrificed,and lungs were removed for microscopic examination and for determination of wet/dry lung weight ratio (W/D ratio) and malondialdehyde (MDA) content (by thiobarbituric acid colorimetric method).Results Compared with group Sham,the W/D ratio and MDA content were significantly increased,the serum TNF-α and IL-6 concentrations were significantly increased (P＜0.05),and the pathological changes were significantly aggravated in Sep and HO groups.Compared with group Sep,the W/D ratio and MDA content were significantly decreased,the serum TNF-α and IL-6 concentrations were significantly decreased (P＜0.05),and the pathological changes were significantly attenuated in group HO.Conclusion HO-1 protein transduction can attenuate acute lung injury in septic rats,and the mechanism is probably related to inhibition of lipid peroxidation in lung tissues and systemic inflammatory responses.

Objective To investigate the effects of heme oxygenase-1 (HO-1) protein transduction mediated by cell penetrating peptide PEP-1 on intestinal injury in a rat model of sepsis induced by cecal ligation and puncture (CLP).Methods Twenty-four healthy male Sprague-Dawley rats,aged 7-9 weeks,weighing 210-260 g,were randomly divided into 4 groups (n =6 each) using a random number table:sham operation group (group S),group CLP,low-dose fusion protein PEP-1-HO-1 + CLP group (group P1) and high-dose fusion protein PEP-1-HO-1 + CLP group (group P2).Fusion protein PEP-1-HO-1 0.3 mg was administrated via the left iliac vein at 1 h before CLP and 5 h after CLP in group P1.Fusion protein PEP-1-HO-1 0.6 mg was administrated via the left iliac vein at 1 h before CLP and 5 h after CLP in group P2.The equal volume of normal saline was given instead of PEP-1-HO-1 in the other groups.The animals underwent laparotomy,but the caecum was not ligated or punctured in group S.Blood samples were collected at 12 h after CLP from the right common carotid artery for measurement of serum TNF-α and IL-6 levels.The rats were then sacrificed and intestines were removed for microscopic examination and for determination of malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in intestinal tissues.Results Compared with group S,the serum TNF-α and IL-6 levels,and MDA content in intestinal tissues were significantly increased,while SOD activity in intestinal tissues was decreased in CLP,P1 and P2 groups.Compared with group CLP,the serum TNF-α and IL-6 levels,and MDA content in intestinal were significantly decreased,while SOD activity in intestinal tissues was increased in P1 and P2 groups.Compared with group P1,the serum TNF-α and IL-6 levels,and MDA content in intestinal tissues were significantly decreased,while SOD activity in intestinal tissues was increased in group P2.The pathological changes of intestines were significantly mitigated in P1 and P2 groups as compared with group CLP.Conclusion HO-1 protein transduction attenuates intestinal injury induced by sepsis in rats,and the mechanism is related to inhibition of systemic inflammatory responses and lipid peroxidation in intestinal tissues.

Objective To evaluate the effects of heme oxygenase-1 (HO-1) mediated by cell penetrating peptide PEP-1 on liverinjury induced by intestinal ischemia/reperfusion (I/R) in rats.Methods Twenty-four male Sprague-Dawley rats,aged 7-9 weeks,weighing 210-260 g,were randomly divided into 3 groups (n =8 each):sham operation group (group S),intestinal I/R group (group I/R) and PEP-1/HO-1 group (group HO).To establish a model of intestinal I/R,intestines were exteriorized and the superior mesenteric artery was exposed and occluded for 45 min ischemia,and then the clamp was removed for 120 min reperfusion.The PEP-1/HO-1 fusion protein 0.5 mg was injectedvia ihe left iliac vein 30 min prior to ischemia in group HO.The superior mesenteric artery was only exposed but not occluded in group S.At the end of reperfusion,blood samples were collected from the right common carotid artery for measurement of serum aspartate aminotransferase (AST),alanine aminotransferase (ALT) activities.The rats were then sacrificed and livers were removed for microscopic examination and for determination of malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in livertissues.Results Compared with group S,serum AST and ALT activities and MDA content in liver tissues were significantly increased,while SOD activity in liver tissues was decreased in groups I/R and HO (P ＜ 0.05).Compared with group I/R,serum AST and ALT activities and MDA content in liver tissues were significantly decreased,while SOD activity in liver tissues was increased in group HO (P ＜0.05).Liver injury induced by intestinal I/R was significantly attenuated in group HO compared with group I/R (P ＜ 0.05).Conciusioon HO-1 protein mediated by cell penetrating peptide PEP-1 can attenuate liver injury induced by intestinalI/R in rats.

Objective To investigate the effects of heme oxygenase-1 (HO-1) transduced by cell penetrating peptide PEP-1 on renal ischemia/reperfusion (I/R) injury in rats.Methods Eighteen male Sprague-Dawley rats,aged 7-9 weeks,weighing 210-260 g,were randomly divided into 3 groups (n =6 each):sham operation group (group S),renal I/R injury group (group I/R) and fusion protein PEP-1/HO-I + I/R group (group HO).I/R injury was produced by occluding bilateral renal arteries for 45 min followed by reperfusion for 6 h.The fusion protein PEP-1/HO-1 was injected via the left iliac vein 30 min prior to ischemia in group HO.Bilateral renal arteries were only exposed but not occluded in group C.Blood samples were collected from the right common carotid artery at 6 h of reperfusion for determination of serum blood urea nitrogen (BUN) and creatinine (Cr) concentrations.The malondialdehyde (MDA) content,superoxide dismutase (SOD) activity and HO-1 expression in renal tissues were measured.Results Compared with group S,the levels of MDA,serum BUN and Cr were significantly increased,the SOD activity was decreased,and HO-1 expression was up-regulated in groups I/R and HO (P ＜0.05).Compared with group I/R,the levels of MDA,serum BUN and Cr were significantly decreased,the SOD activity was increased,and HO-1 expression was up-regulated in group HO (P ＜ 0.05).Conclusion HO-1 protein can be successfully transduced into renal tissues by PEP-1 and transduced HO-1 protein reduces renal I/R injury by inhibiting lipid peroxidation response.