Objective:To investigate the protective effect of quercetin(QUE)on acute lung injury(ALI)rats with sepsis.Methods:Sixty male SD rats were randomly divided into 6 groups(n=10):Sham operation group(Sham),model group(CLP),QUE 25 mg/kg group,QUE 50 mg/kg group,QUE 100 mg/kg group and positive drug dexamethasone(DEX)group.Rats in each group were continuously treated for 7 days,and the survival rate was calculated;HE staining and lung wet-to-dry weight ratio(W/D)were used to evaluate the severity of lung injury;TUNEL staining was used to detect lung tissue apoptosis;levels of inflammatory factors,SOD and MDA were detected by the kits;Western blot was used to detect expressions of apoptosis-related proteins and phosphoryla-tion levels of PTEN,β-catenin,protein kinase B(AKT)and glycogen synthase kinase-3β(GSK-3β)in rat lung tissue.Results:Com-pared with CLP group,after QUE 50 mg/kg and 100 mg/kg treatment,survival rate of rats was significantly increased(P<0.05),the degree of inflammatory cell infiltration in lung tissue was reduced,lung injury score and W/D were reduced(P<0.05),apoptosis rate of lung tissue cells and expressions of apoptosis-related proteins were significantly decreased(P<0.05),levels of inflammatory factors were decreased(P<0.05),while the antioxidant capacity was enhanced(P<0.05),phosphorylation levels of PTEN and β-catenin were decreased,while phosphorylation levels of AKT and GSK-3β were increased(P<0.05).Conclusion:QUE protects rats from ALI with sepsis by inhibiting apoptosis,reducing inflammation and antioxidance,which mechanism may be related to PTEN/β-catenin and AKT/GSK-3β pathways.

The management of hospital volunteers is one of the main tasks of medical social workers.In practical work,they are often in a dilemma due to ethical problems,which restricts the scientific development of hospital volunteer organizations.Based on the experience of frontline medical social workers in the"Guangji Boat"Volunteer Service Alliance of the Second Affiliated Hospital Zhejiang University School of Medicine,while investigating other public hospitals,this paper summarized and organized ethical issues,analyzed their causes,and proposed improvement strategies.The ethical dilemma of hospital volunteer service was mainly in the conflict between the dual relationship of human emotion and norm,the conflict between incentive mechanism and non-reward value,as well as the conflict between participation motivation and organizational goal.The ethical dilemma in the management of hospital volunteers was attributed to the lack of standardized practical operation systems.Based on the above ethical dilemmas,combined with the development experience of volunteer service in public hospitals,this paper proposed reasonable countermeasures to provide a reference for the management of hospital volunteers.

Inflammatory bowel disease (IBD) is characterized by recurrent non ⁃ specific intestinal inflammatory responses. Intestinal fibrosis is an important cause of IBD complicated with intestinal obstruction. Nuclear factor erythroid 2⁃ related factor 2 (Nrf2) is a transcription factor that has anti ⁃ oxidative stress response in cells. In IBD, Nrf2 and its downstream regulated antioxidant enzymes achieve protective effects against intestinal fibrosis by inhibiting the activation of nuclear factor ⁃ κB, regulating T helper cell 17/regulatory T cell balance of intestinal immunity, and inhibiting transforming growth factor⁃β1/Smads signaling pathway. In this review, the structure of Nrf2, the specific mechanism of Nrf2's effect on intestinal fibrosis in IBD, and the recent studies on the treatment of IBD through Nrf2 pathway were reviewed in an attempt to provide a new direction for the prevention and treatment of IBD.

【Objective】 To explore the expressions of PBRM1 and PD-L1 in renal cell carcinoma (RCC), and the molecular mechanism of PBRM1 regulating PD-L1, in order to provide experimental results for clinical immunotherapy. 【Methods】 The protein expressions of PBRM1 and PD-L1 were detected with immunohistochemistry, and their mRNA expressions were determined by analyzing TCGA database. Meanwhile, the relationship between overall survival and mRNA expressions of PBRM1 and PD-L1 were analyzed in TCGA database. The exosomes were extracted with exoEasy Maxi Kit. Expressions of exosomal biomarkers CD63 and CD9 were detected with Western blotting, and their morphology was observed with transmission electron microscope. PD-L1 expression after IFN-γ, IL-6 and TNF-α treatment was detected with Western blotting. 【Results】 The expression of PBRM1 was significantly lower in canver tissue than in paracancerous tissue (P<0.001). The loss rate of PBRM1 was up to 76.4%. PBRM1 expression was not correlated with PD-L1 expression. PBRM1 deletion activated TNF-α/exosome signaling pathway, leading to increase of PD-L1 secretion in exosomes, which was then transported to the outside of cells. 【Conclusion】 There is no relationship between PBRM1 and PD-L1 protein expressions in RCC. However, PBRM1 mutation can lead to inflammatory signaling pathway activation, inducing PD-L1 secretion, which is encapsulated in exosomes and transported to the outside of cells, and affects the response of immunotherapy.

Bcr-Abl threonine 315 to isoleucine 315 (T315I) gatekeeper mutation induced drug resistance remains an unmet clinical challenge for the treatment of chronic myeloid leukemia (CML). Chemical degradation of Bcr-Abl

Objective: To study the oxidative damage of di- (2-ethylhexyl) phthalate (DEHP) on MCF-7 cells, and to investigate the effects of 3β-hydroxysteroid dehydrogenase (3β-HSD) gene silence or overexpression on DEHP-induced oxidative damage. Methods: MCF-7 cells, 3β-HSD gene silencing cells and 3β-HSD gene overexpression cells were treated with different doses of DEHP (0,0.05,0.1,0.2,0.4,0.8 mmol/L) for 24h, then intracellular oxidative damage index such as MDA, SOD, GSH, GSH-PX were detected, DNA repair gene hOGG1, hMTH1 mRNA expression were tested by Q-PCR, hOGG1, hMTH1 protein expression were detected by western blot. Results: After MCF-7 cells were treated by DEHP, MDA levels increased; SOD activity, GSH content, GSH-PX activity decreased, hOGG1 and hMTH1 mRNA expression levels increased, hOGG1 and hMTH1 protein expression levels increased, the differences were statistically significant when compared with control (P<0.05 or P<0.01) . In 3β-HSD gene silencing cells which were treated by DEHP, when compared with the same dose group of MCF-7 cells, MDA content increased, SOD activity, GSH content, GSH-PX activity decreased, hOGG1 and hMTH1 mRNA expression levels decreased, hOGG1 and hMTH1 protein expression levels decreased, the difference were statistically significant (P<0.05 or P<0.01) . In 3β-HSD gene overexpression cells which were treated by DEHP, when compared with the same dose group of MCF-7 cells, MDA content decreased; SOD activity, GSH content, GSH-PX activity increased, of hOGG1 and hMTH1 mRNA expression levels increased, hOGG1 and hMTH1 protein expression levels increased, the difference were statistically significant (P<0.05 or P<0.01) . Conclusion DEHP could cause oxidative damage in MCF-7 cells, induce the changes of related genes and proteins, 3β-HSD plays an antioxidant role in the process of DEHP ox-idative damage.

Optical coherence tomography angiography (OCTA) base on OCT with an algorithm that can image a high-resolution picture of retinal circulation. OCTA has allowed quantifying the characteristic lesions of diabetic retinopathy (DR) in early stage, such as fovea avascular zone, retinal vascular density and the counts of retinal microaneurysm. In addition, OCTA can objectively evaluate the progression and prognosis of DR in late stage through imaging involved retinal neovascularization. Understanding OCT angiography features of DR lesions with different course of the disease may provide reference value for the diagnosis and treatment of DR.

Objective To observe the changes of four quantitative indexes of diabetic macular edema by using optical coherence tomography.Methods Eighty-nine patients (155 eyes) with diabetic retinopathy were included in this project and were divided into two groups according to the present of diabetic macular edema:Negative group (56 cases,100 eyes) and positive group(33 cases,55 eyes).In addition,23 cases (42 eyes) of normal volunteers constituted the normal control group.All the objects accepted an optical coherence tomography examination and the indexes including central retinal thickness (CRT),subfoveal choroidal thickness (SFCT) and integrity of external limiting membrane(ELM) as well as inner/outer segment (IS/OS) were measured and analyzed.Results The average CRT of positive group (219.048 ± 16.798) μm was significantly thicker than that of control group(217.775 ± 26.866) μm and negative group (280.418 ±74.187) μm (P ＜0.001).Mean SFCT among control group (312.893 ±140.559) μm,negative group (302.080 ± 125.287) μm and positive group (293.745 ±140.517) μm had no statistical significance (P =0.781).There were 3 eyes with disrupted ELM layer in the negative group and 8 eyes in the positive group.Difference between them was proved to be significant (P =0.019).Similarly,the integrity of IS/OS layer had significant difference between negative group (5 eyes disrupted) and positive group (19 eyes disrupted) (P ＜ 0.001).Conelusion CRT of patients with diabetic macular edema is always increased and the integrity of ELM or (and) IS/OS can be disrupted in many cases.Indexes including CRT and the integrity of ELM or (and) IS/OS can be used to evaluate the severity of diabetic macular edema quantificationally.

Objective: To provide an important tool for the study of diagnose and treatment of prostate cancer (PCa) osseous metastasis and change of bone stress force on prostate cancer (PCa) osseous metastasis and a platform, which is more congruous to clinical process, for prevention and cure of neoplastic bone metastases, and to carry out the construction and improvement of animal models of PCa with different positional osseous metastasis in vivo.Methods: Different gradient concentrations of RM-1 cells were inoculated into the cavity of left femoral bone or lumbar vertebra of mice (C57BL/6) respectively.The change of mouse activity, tumor formation, tumor size and survival time were observed respectively.And the femur tissue and spinal tissue were obtained from the mice after death.The gray value of iconography were measured by imageological examination of femur tissue, and the final histopathological examination were taken to determine the tumor type in both femur and spinal tissue.Results: The tumor growth could be touched at the puncture site in all the mice after inoculated for 7 days.There were no obvious differences in the time of tumorigenesis, the rate of tumor growth and tumor size among the mice in the same group (P>0.05).As the result, the construction femoral bone and lumbar vertebra metastatic models of PCa had been confirmed by iconography and pathology detection.At the same time, the survival time of the mice inoculated with low concentrations of PCa cells was obviously longer than that of high concentrations of PCa cells (at least 2 weeks longer).Conclusion: The animal models with different positional osseous metastasis (limbs and axial skeleton) of PCa using the same PCa cells (RM-1) had been first constructed successfully in our study.At the same time, a high success rate of construction of PCa animal model with bone metastasis was obtained by femoral bone marrow cavity injection of PCa cells.The rate of tumor growth was rapid, animal survival time was appropriate, and the PCa animal model with bone metastasis can be stably reproduced by our method.These animal models can be used to explore the pathogenesis of different positional PCa bone metastasis and provide a new platform, which were more congruous to clinical process, for prevention and cure of neoplastic bone metastases.

Objective To design and synthesize novel triazole antifungal derivatives with 1 ,3 ,4-oxadiazole side chain for the study of antifungal activities. Methods Fourteen title compounds were synthesized via acylation ,aminolysis reaction ,cy-clization ,nucleophilic substitution ,etc. All the compounds were characterized by 1 H NMR ,MS spectra. The in vitro antifun-gal activities were evaluated against six human pathogenic fungi through the micro-broth dilution method. Results The title compounds exhibited strong antifungal activities against all the tested fungi ,especially against Candida albicans. Compounds 10d ,10i , 10l , and 10n were found to be the most effective , with a minimum inhibitory concentration (MIC80 ) of 0.003 9 μg/ml .They are 16-fold more potent than ICZ ( MIC80 0.062 5 μg/ml) and 64-fold more potent than FCZ (MIC80 0.25 μg/ml) .Conclusion The 1 ,3 ,4-oxadiazole side chain could affect the antifungal activities. That could be due to the prop-er incorporation between the 1 ,3 ,4-oxadiazole substituted phenyl ring with the target enzyme.