1.Rutin alleviates neuroinflammation in rats with hydraulic shock brain injury by inhibiting the TXNIP/NLRP3 signaling pathway
Wei XU ; Shan ZHANG ; Dezhen YANG ; Huichang TANG ; Xiaojun FENG ; Haichang LI ; Chengzhou HU
Immunological Journal 2024;40(10):767-772
Objective To investigate the influence of rutin on neuroinflammation in rats with hydraulic shock brain injury by regulating thioredoxin-interacting protein(TXNIP)/NOD-like receptor protein 3(NLRP3)signaling pathway.Methods Rats were randomly separated into model group and sham operation group;the rats in the model group were established by hydraulic impact method.After modeling,they were randomly separated into rutin low(rutin-L,25 mg·kg-1 rutin)and medium(rutin-M,50 mg·kg-1 rutin).D),high(rutin-H,100 mg·kg-1 rutin)dose groups,model group and positive control group(dexamethasone group,0.1 mg·kg-1 dexamethasone),18 animals/group.Each group was intervened with drugs and normal saline once a day,and after continuous intervention for 3 days,the neurological deficit(neurological severity score,NSS)of the rats was scored;the rats were sacrificed by decapitation,the cerebral edema was determined,the brain tissue around the contusion was separated,and the histological changes,inflammatory cytokine indicators-tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)levels and TXNIP,NLRP3 protein expression levels were measured.Results The rats in the sham operation group had no injury.The integrity of brain tissue in model group was damaged,cell wrinkly nuclei were deeply stained,interstitial edema was accompanied by holes and the TNF-α and IL-1β levels,NSS score,cerebral edema,TXNIP and NLRP3 protein expression levels were all increased compared with those in the sham operation group(P<0.05);after rutin intervention,the pathological injury of rat brain tissue was relieved,and the TNF-α and IL-1β levels,NSS score,cerebral edema,TXNIP,and NLRP3 protein expression levels were all lower than those in the model group(P<0.05),there was no significant difference between the rutin-H group and the dexamethasone group(P>0.05).Conclusion Rutin can inhibit the inflammatory response of hydraulic shock brain injury rats,improve brain tissue injury and edema,which may be related to the inhibition of TXNIP/NLRP3 signaling pathway.
2.Rutin alleviates neuroinflammation in rats with hydraulic shock brain injury by inhibiting the TXNIP/NLRP3 signaling pathway
Wei XU ; Shan ZHANG ; Dezhen YANG ; Huichang TANG ; Xiaojun FENG ; Haichang LI ; Chengzhou HU
Immunological Journal 2024;40(10):767-772
Objective To investigate the influence of rutin on neuroinflammation in rats with hydraulic shock brain injury by regulating thioredoxin-interacting protein(TXNIP)/NOD-like receptor protein 3(NLRP3)signaling pathway.Methods Rats were randomly separated into model group and sham operation group;the rats in the model group were established by hydraulic impact method.After modeling,they were randomly separated into rutin low(rutin-L,25 mg·kg-1 rutin)and medium(rutin-M,50 mg·kg-1 rutin).D),high(rutin-H,100 mg·kg-1 rutin)dose groups,model group and positive control group(dexamethasone group,0.1 mg·kg-1 dexamethasone),18 animals/group.Each group was intervened with drugs and normal saline once a day,and after continuous intervention for 3 days,the neurological deficit(neurological severity score,NSS)of the rats was scored;the rats were sacrificed by decapitation,the cerebral edema was determined,the brain tissue around the contusion was separated,and the histological changes,inflammatory cytokine indicators-tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)levels and TXNIP,NLRP3 protein expression levels were measured.Results The rats in the sham operation group had no injury.The integrity of brain tissue in model group was damaged,cell wrinkly nuclei were deeply stained,interstitial edema was accompanied by holes and the TNF-α and IL-1β levels,NSS score,cerebral edema,TXNIP and NLRP3 protein expression levels were all increased compared with those in the sham operation group(P<0.05);after rutin intervention,the pathological injury of rat brain tissue was relieved,and the TNF-α and IL-1β levels,NSS score,cerebral edema,TXNIP,and NLRP3 protein expression levels were all lower than those in the model group(P<0.05),there was no significant difference between the rutin-H group and the dexamethasone group(P>0.05).Conclusion Rutin can inhibit the inflammatory response of hydraulic shock brain injury rats,improve brain tissue injury and edema,which may be related to the inhibition of TXNIP/NLRP3 signaling pathway.
3.Preclinical efficacy against acute myeloid leukaemia of SH1573, a novel mutant IDH2 inhibitor approved for clinical trials in China.
Zhiqiang WANG ; Zhibo ZHANG ; Yong LI ; Li SUN ; Dezhen PENG ; Danyu DU ; Xian ZHANG ; Luwei HAN ; Liwen ZHAO ; Ligong LU ; Hongzhi DU ; Shengtao YUAN ; Meixiao ZHAN
Acta Pharmaceutica Sinica B 2021;11(6):1526-1540
Acute myeloid leukaemia (AML) is the most common form of acute leukaemia in adults, with increasing incidence with age and a generally poor prognosis. Almost 20% of AML patients express mutant isocitrate dehydrogenase 2 (mIDH2), which leads to the accumulation of the carcinogenic metabolite 2-hydroxyglutarate (2-HG), resulting in poor prognosis. Thus, global institutions have been working to develop mIDH2 inhibitors. SH1573 is a novel mIDH2 inhibitor that we independently designed and synthesised. We have conducted a comprehensive study on its pharmacodynamics, pharmacokinetics and safety. First, SH1573 exhibited a strong selective inhibition of mIDH2 R140Q protein, which could effectively reduce the production of 2-HG in cell lines, serum and tumors of an animal model. It could also promote the differentiation of mutant AML cell lines and granulocytes in PDX models. Then, it was confirmed that SH1573 possessed characteristics of high bioavailability, good metabolic stability and wide tissue distribution. Finally, toxicological data showed that SH1573 had no effects on the respiratory system, cardiovascular system and nervous system, and was genetically safe. This research successfully promoted the approval of SH1573 for clinical trials (CTR20200247). All experiments demonstrated that, as a potential drug against mIDH2 R140Q acute myeloid leukaemia, SH1573 was effective and safe.
4.Effects of hyperbaric oxygen combined with salmeterol xinafoate and fluticasone propionate powder for inhalation on pulmonary function and serum levels of COX-2 and MMP-9 in patients with stable COPD
Dezhen ZHANG ; Ce SHI ; Anmeng WEI
Chinese journal of nautical medicine and hyperbaric medicine 2021;28(3):326-329
Objective:To explore the effects of hyperbaric oxygen (HBO) combined with salmeterol xinafoate and fluticasone propionate powder for inhalation (trade name: Seretide) on pulmonary function and serum levels of cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9) in patients with stable chronic obstructive pulmonary disease (COPD).Methods:A total of 96 patients with stable COPD treated in the First People’s Hospital of Shangqiu from February 2019 to February 2020 were selected and randomly divided into control group ( n=48) and observation group ( n=48) by the random number table method. The control group was treated with salmeterol xinafoate and fluticasone propionate powder for inhalation (50 μg salmeterol and 250 μg fluticasone propionate), and the observation group was treated with HBO on the basis of the treatment of the control group. The clinical efficacy, symptom disappearance time, pulmonary function measured by forced respiratory volume in one second (FEV1) before and after treatment, the ratio of FEV to forced vital capacity (FEV/FVC) and the ratio of FEV1 to predicted value (FEV1/Pred), and the serum levels COX-2 and MMP-9 were compared between the two groups. Results:The total effective rate of the observation group (97.92%) was significantly higher than that of the control group (83.33%), with a statistically significant difference ( P<0.05). After treatment, the recovery time of normal body temperature, the disappearance time of cough and lung rale, and the recovery time of leukocytes in the observation group were significantly shorter than those in the control group, and the differences were statistically significant ( P<0.05 or P<0.01). After treatment, the levels of FEV1, the ratios of FEV/FVC and FEV1/Pred in the observation group were significantly higher than those in the control group, while the serum levels of COX-2 and MMP-9 in the observation group were significantly lower than those in the control group, and the differences were statistically significant ( P<0.01). Conclusion:HBO combined with salmeterol xinafoate and fluticasone propionate powder for inhalation has significant clinical effects on patients with stable COPD by improving their pulmonary function and reducing their serum levels of COX-2 and MMP-9.
5.Effects of hyperbaric oxygen combined with salmeterol xinafoate and fluticasone propionate powder for inhalation on pulmonary function and serum levels of COX-2 and MMP-9 in patients with stable COPD
Dezhen ZHANG ; Ce SHI ; Anmeng WEI
Chinese journal of nautical medicine and hyperbaric medicine 2021;28(3):326-329
Objective:To explore the effects of hyperbaric oxygen (HBO) combined with salmeterol xinafoate and fluticasone propionate powder for inhalation (trade name: Seretide) on pulmonary function and serum levels of cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9) in patients with stable chronic obstructive pulmonary disease (COPD).Methods:A total of 96 patients with stable COPD treated in the First People’s Hospital of Shangqiu from February 2019 to February 2020 were selected and randomly divided into control group ( n=48) and observation group ( n=48) by the random number table method. The control group was treated with salmeterol xinafoate and fluticasone propionate powder for inhalation (50 μg salmeterol and 250 μg fluticasone propionate), and the observation group was treated with HBO on the basis of the treatment of the control group. The clinical efficacy, symptom disappearance time, pulmonary function measured by forced respiratory volume in one second (FEV1) before and after treatment, the ratio of FEV to forced vital capacity (FEV/FVC) and the ratio of FEV1 to predicted value (FEV1/Pred), and the serum levels COX-2 and MMP-9 were compared between the two groups. Results:The total effective rate of the observation group (97.92%) was significantly higher than that of the control group (83.33%), with a statistically significant difference ( P<0.05). After treatment, the recovery time of normal body temperature, the disappearance time of cough and lung rale, and the recovery time of leukocytes in the observation group were significantly shorter than those in the control group, and the differences were statistically significant ( P<0.05 or P<0.01). After treatment, the levels of FEV1, the ratios of FEV/FVC and FEV1/Pred in the observation group were significantly higher than those in the control group, while the serum levels of COX-2 and MMP-9 in the observation group were significantly lower than those in the control group, and the differences were statistically significant ( P<0.01). Conclusion:HBO combined with salmeterol xinafoate and fluticasone propionate powder for inhalation has significant clinical effects on patients with stable COPD by improving their pulmonary function and reducing their serum levels of COX-2 and MMP-9.
6. Effectiveness evaluation of the Thyroid Imaging Report and Data System proposed by American Radiological Society (2017) (ACR-TIRADS) for differential diagnosis in thyroid nodules
Yuzhi ZHANG ; Ting XU ; Jingyu GU ; Xinhua YE ; Shuhang XU ; Yang WU ; Xinyu SHAO ; Dezhen LIU ; Weiping LU ; Fei HUA ; Bimin SHI ; Jun LIANG ; Lan XU ; Wei TANG ; Chao LIU ; Xiaohong WU
Chinese Journal of Ultrasonography 2018;27(6):505-509
Objective:
To evaluate the effect of the Thyroid Imaging Report and Data System proposed by American Radiological Society (ACR-TIRADS) for differential diagnosis in thyroid nodules, and compare ACR-TIRADS to the TIRADS proposed by Kwak et al.(K-TIRADS) and the ultrasound-based risk stratification system evaluated by American Thyroid Association (ATA-Risk Stratification).
Methods:
The clinical data of 1 760 patients with 1 912 thyroid nodules from 8 hospitals in Jiangsu province were retrospectively analysed. All of them were categorized based on ultrasound-based risk stratification systems. The ROC curve was established to assess and compare the diagnostic value of the systems.
Results:
The area under the ROC curve (AUC) of ACR-TIRADS was 0.830, with high sensitivity and negative predictive value (86.9% and 87.5%, respectively), and relatively low specificity and positive predictive value (64.1% and 62.9%, respectively). The sensitivity and specificity of K-TIRADS were up to 84.9% and 76.1%, respectively. The AUC of ATA-Risk Stratification was 0.852, with relatively high specificity (83.4%), and low sensitivity (79.4%). There were significant differences in the AUC among the three ultrasound-based risk stratification systems, of which K-TIRADS was the highest (
7.Genetic diversities of different geographical populations of Aedes albopictus based on mitochondrial gene COI
Ruiling ZHANG ; Guangqin YAO ; Xiaoqian PAN ; Dezhen MA ; Aihua ZHAO ; Zhong ZHANG
Chinese Journal of Zoonoses 2017;33(4):316-320
In order to figure out phylogenetic relationship and genetic diversity of different geographical populations,genetic analyses of Aedes albopictus were performed based on mitochondrial gene COI.Based on samples collected from most distribution regions in China,mitochondrial gene Cytochrome C Oxidase Subunit I was obtained through PCR and DNA sequence.Together with some COI sequences downloaded from GenBank,60 COI sequences with the final length of 598 bp were used for subsequent analyses.Results showed that there was no obvious divergence according to phylogenetic analyse,all sequences were clustered together in Maximum Likelihood tree.Sixteen haplotypes were detected,and four of them shared haplotypes.Haplotype diversity (Hd) was 0.737,nucleotide diversity (π) was 0.20 %.Population genetic differentiation analyses demon strated that Hainan population showed obvious divergences.In the network of haplotypes,H1 and H6 was found to be the primary haplotypes,and they formed two radical centers.All these results indicate that A.albopictus populations of China are expanding presently,and Hainan population become differential with other geographical populations,which probably attribute to geographical isolations.
8.Epidemiological situation of human parasitic diseases through three investi-gations in Jinhu County,Jiangsu Province
Shumei LI ; Daokuan SUN ; Cuiping ZHANG ; Dezhen CHEN ; Qian LI
Chinese Journal of Schistosomiasis Control 2016;28(4):450-452,455
Objective To understand the epidemiological situation of human parasitic diseases in Jinhu County,so as to pro?vide the evidence for formulating further control strategy. Methods The investigated local residents were sampled by the ran?dom cluster sampling method in 1989,1999 and 2015. The infections of intestinal helminthes were detected by Kato?Katz tech?nique,the eggs of Enterubius vermicularis were examined by cellophane anal swab for children,the intestinal protozoa were ex?amined by the saline smear and iodine staining methods. Results The total rates of parasitic infections were 62.57%,9.32%and 0.49%in 1989,1999 and 2015,respectively. Compared to those in 1989 and in 1999,the infection rate in 2015 was de?creased by 99.22%and 94.74%,respectively. The numbers of detected parasite species were 14,10 and 4 in 1989,1999 and 2015,respectively. The intensities of infections were mainly mild in three investigations,and the intensities of all the infections in 2015 were mild. The species of infected parasites were mainly single,however,multiple infections were observed in 1989,in?cluding 4 parasite species(0.72%)and 3 parasite species(7.02%). Only in 1989,the difference between sexes was significant and the infection rate of the female was higher than that of the male(χ2=18.01,P<0.01). Conclusions The infection rates of human parasites are decreased gradually and stabilized at the low level in Jinhu County. However,the surveillance work still should be strengthened to consolidate the achievement.
9.Evaluation of integrated control measures for soil-transmitted nematodiasis in Jinhu County,Jiangsu Province
Daokuan SUN ; Cuiping ZHANG ; Dezhen CHEN ; Shumei LI ; Qian LI ; Quanfeng WANG
Chinese Journal of Schistosomiasis Control 2014;(1):69-71
Objective To evaluate the effect of integrated control measures on soil-transmitted nematodiasis so as to provide the evidence for formulating the appropriate control strategies and measures in Jinhu County,Jiangsu Province. Methods Since 1995,the comprehensive control measures were carried out for soil-transmitted nematodiasis,and the measures included deworm-ing,health education,safe water,sanitation and environmental remediation. The effects of the comprehensive control measures were evaluated by the investigations of the prevalence of soil-transmitted nematodiasis,awareness of health knowledge,and behav-iors of residents. Results From 1995 to 2012,646 437 person-times were administrated in deworming medication with 2.48 times per capita;the benefit rate of safe water was 97.90%;the popularity rate of harmless toilets was 86.89%. The awareness rate of health knowledge increased from 54.05%in 1996 to 95.60%in 2012,the difference between them were statistically significant (χ2=230.92,P<0.01);the rate of correct health behaviors increased from 59.07%in 1996 to 96.40%in 2012,the difference between them had statistical significance(χ2=202.69,P<0.01). The prevalence of soil-transmitted nematodiasis decreased from 62.57%in 1989 to 1.21%in 2012,the difference had statistical significance(χ2=1 016.92,P<0.01). The infection rates of Asca-ris lumbricodes,hookworm and Trichuris trichiura were 0.58%,1.12%and 0,respectively in 2012,and compared with the rates of those infections in 1989,the decline rates were 94.96%,97.28%and 100%respectively,the differences between them were sta-tistically significant(χ2A sc aris =129.50,χ2hookworm=544.62,χ2Tri ch uris =254.19,all P<0.01). Conclusion The comprehensive control strategies and measures are effective and soil-transmitted nematodiasis has been controlled in Jinhu County.
10.Research on peripheral T, B cell subsets and NK cells under different immune status and hepatitis B cirrhosis with chronic HBV infection
Min ZHANG ; Lisha YANG ; Dezhen PENG ; Bing ZHANG ; Lin NIE
The Journal of Practical Medicine 2014;(20):3233-3236
Objective To explore the percentage changes of peripheral T , B cell subsets and NK cells in chronic HBV infectors under different immune states and hepatitis B cirrhosis . Methods Seventy-five chronic HBV infectors, including 20 cases with immune clearance, 20 cases with immunodeficiency (inactive) and 35 cases with cirrhosis, and 20 healthy control were enrolled. The percentages of peripheral T and B lymphocyte subsets and NK cells were detected by Flow Cytometry. The differences of the groups were analyzed. Results Comparing with the control group, CD4+T cells were decreased in the other four groups (P<0.05). The sequence of CD4+T cells, from high to low, was the control group, the immunodeficiency group, the immune clearance group, the compensated cirrhosis group and the de-compensated cirrhosis group. CD4+/CD8+T cell and NK cell were lower , but CD8+T cell and B cell were higher in immune clearance group than that of the control group (P < 0.05). Patients in immunodeficiency group had lower ratio of CD4+/CD8+T cell and higher CD8+T cell than those in the control group (P < 0.05). In all the groups, patients with de-compensated cirrhosis showed highest ratio of CD4+ to CD8+ T cells and B cells, but lowest CD3+T, CD8+ T and NK cells (P < 0.05). Conclusions Results suggests immune dysfunction exists in patients with chronic HBV infection. It has potential clinical value in understanding patients′ immune states and progression of disease by detecting peripheral blood lymphocyte subsets and NK cells.

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