2.Distribution characteristics of rs10975521 A/T and rs1929992 A/G polymorphism of IL-33 gene in Guangxi population
Jing GUO ; Yang XIANG ; Youfan PENG ; Yesheng WEI ; Yan LAN
Chinese Journal of Immunology 2016;32(6):849-852
Objective: To study and explore the distribution characteristics of rs10975521A/T and rs1929992A/G polymorphism of the IL-33 gene in Chinese Guangxi population. To compare the frequency distribution differences of allele and genotype of two sites among different ethnic. Methods:The polymorphism of rs10975521A/T and rs1929992A/G of IL-33 gene in 283 subjects were analyzed with the methods of Single base extension (PCR-SEB) and DNA sequencing,and the distribution frequency and the differences between groups of that were analyzed statisticaly. Results:Three genotypes of AA,AT and TT were found in rs10975521A/T with the frequency distribution of 12. 7%,53. 0% and 34. 3% respectively and there was no significant difference between sexes of each genotype and allele frequency in the Guangxi population ( P>0. 05 ) . There were significant differences of the allele frequency of rs10975521A/T in the Guangxi population compared with that in the European (P< 0. 05), han Chinese in Bejing (P< 0. 05) and Japanese people (P< 0. 01). Three genotypes of AA,AG and GG were found in rs1929992A/G with the frequency distribution of 23. 9%,53. 7% and 13. 4% respectively and there was no significant difference between sexes of each genotype and allele frequency in the Guangxi population(P> 0. 05),but the differences of genotype frequency of rs1929992A/G was statistically significant compared with that in the European,han Chinese in Bejing and Japanese people ( P< 0. 05 ) . There were significant differences of the allele frequency between Guangxi population and European (P< 0. 01),han Chinese in Bejing(P< 0. 05). Conclusion: There are different degrees of discrepancy of rs10975521A/T and rs1929992A/G polymorphism of IL-33 gene among different race and region.
3.Resveratrol activates Notch signalling pathway via Sirtuin 1 in podocytes
Kewei XIE ; Kai WEI ; Mingying GU ; Peng XIANG ; Leyi GU
Chinese Journal of Nephrology 2015;31(4):296-302
Objective To explore the relationship between resveratrol and Notch 1 signalling pathway in podocytes.Methods Interference RNA (RNAi) and doxycycline (Dox) were used to inhibit the Sirtuin (SIRT) 1 expression in the wild-type and inducible SIRT1 shRNA (CAGGS) podocytes respectively.Recombinant mouse delta-like ligand 4 (DLL4) was used to activate Notch1 signalling.The message RNA of SIRT1,Notch1 downstream gene Hes1 and Hey2,as well as the key enzymes of Notch1 signalling pathway were detected by using real-time PCR.Western blotting was used to detect intracellular domain of Notch 1 (ICD1),SIRT1,and metalloprotease (ADAM) 10 and components of γ-secretase complex protein expression.Results In WT murine podoytes,resveratrol up-regulated ICD1 protein production,as well as the mRNA of Hes1 and Hey2 in a dose-dependent manner.Treatment with resveratrol resulted Nicastrin mRNA and protein increase in podocytes (P <0.05),as well as inhibit ADAM10 expression (P < 0.05),but all these changes were prevented after the use of SIRT1 RNAi(P < 0.05).DLL4 up-regulated the expression of mRNA of Hes1 and Hey2,as well as ICD1 protein production in a dose-dependent manner.Treatment with doxycycline resulted decrease of SIRT1 gene and protein expression in CAGGS podocytes after 24 h and 48 h respectively(P < 0.05),which weakend the role of DLL4 significantly(P < 0.05).Conclusion Resveratrol induces Nicastrin expression,as well as activation of Notch1 signalling pathway in a SIRT1-dependent manner.
4.Necroptosis Involves in Mechanism of Lung Injury Induced by Intestinal Ischemia-Reperfusion
Peng YANG ; Ming WEI ; Xiang LI ; Shihong WEN ; Kexuan LIU
Journal of Sun Yat-sen University(Medical Sciences) 2017;38(3):321-326
[Objective] To explore whether necroptosis is involved in the mechanism of lung injury induced by intestinal ischemia-reperfusion.[Method] Thirty-two healthy male Sprague-Dawley rats were randomly assigned into 4 groups (n--8):sham operation group (sham group),isehemia/ reperfusion group (I/R group),necroptosis inhibitor necrostatin-1 group (Nec-1 group) and solvent dimethyl sulfoxide (DMSO) group (DMSO group).Model of intestinal I/R injury was produced by clamping the superior mesenteric artery for 1.5 h followed by 6 h reperfusion in rats.Necrostatin-1 1.0 mg/kg was administered 30 min before occlusion in Nec1 group,while the equal volume of DMSO was given instead in DMSO group.The rats were sacrificed at 6 h of reperfusion and the lung tissues were removed for measurement of wet-dry ratio and microscopic examination and scored.The expression of receptor-interacting protein 1 (RIP1) and receptor-interacting protein 3 (RIP3) in lung tissues was detected using Western-blot and immunohistochemistry.[Result] Compared with sham group,lung morphology score and wet/dry ratio in I/R,DMSO group raised (P < 0.05).Lung morphology score and wet/dry ratio statistically declined in Nec-1 group compared with I/R and DMSO group (P < 0.05),while there was no statistical difference of wet/dry ratio between sham group and Nec-1 group (P > 0.05).As the result of westernblot and immunohistochemistry showed,the expression of RIP1 and RIP3 was up-regulated in I/R group and DMSO group (P <0.05),which was inhibited by Nec-1 in Nec-1 group (P < 0.05).[Conclusion] Necroptosis is involved in the mechanism of lung injury induced by intestinal ischemia-reperfusion,and Nec-1,the special inhibitor of RIP1,can reduce the injury.
5.Association between peripheral monocyte CD36 expression and rheumatoid arthritis
Youfan PENG ; Yang XIANG ; Yesheng WEI ; Shimao ZHONG
Chinese Journal of Rheumatology 2016;20(7):441-445
Objective To investigate the association between peripheral monocyte CD36 expression and rheum-atoid arthritis (RA).Methods A total of 108 patients with RA and 108 healthy individuals were included between 2014 and 2015.Disease Activity Score (DAS)28-erythrocyte sedimentation rate (ESR) and DAS28-C reactive protein (CRP) were used to estimate disease activity in patients with RA,and monocyte CD36 fluorescence intensity was determined by using flow cytometry.Student's t test or Mann-Whitney U test was used to compare the differences between the two groups.The categorical data was compared using x2 test.Correlations between variables were analyzed with Spearman correlation,Logistic regression analysis was used to identify risk factors associated with RA,we used receiver operating characteristic (ROC) curve to estimate the performance of relevant variables for RA.Results Low density lipoprotein cholesterin (LDL-C) [(2.8±0.8) mmol/L,(2.6±0.6) mmol/L,t=-2.046,P=0.042],ESR[25.5(18.00,40.00) mm/1 h,10.00(4.60,10.00) mm/1 h,Z=-12.786,P<0.01],CRP [15.9 (6.71,25.43) mg/L,2.28 (1.63,4.60) mg/L,Z=-7.980,P<0.01] and monocyte CD36 expression [(0.44±0.22)×109/L,(081 ±0.26)×109/L,t=1 1.159,P<0.01] was statistically different between the two groups.Of note,monocyte CD36 fluorescence intensity was negatively correlated with disease activity in patients with moderate and severe disease (r=-0.146,P=0.036;r=-0.259,P=0.007).In stepwise Logistic regression analysis,monocyte CD36 fluorescence intensity was independently associated with RA [OR=0.803,P=0.002,95%CI (0.791,0.820)].ROC curve analysis showed a significant performance with area under curve of 0.855 [95%CI (0.807,0.904);P<0.01],the sensitivity and specificity were 80.6% and 73.1%,respectively,the cutoff values was 0.570.Conclusion Monocyte CD36 fluorescence intensity was independently associated with RA in stepwise Logistic regression analysis.A correlation between monocyte CD36 fluorescence intensity and DAS28-CRP,DAS28-ESR was observed in RA patients.
6.Effects of heart displacement on hemodynamics during off-pump coronary artery bypass surgery
Wei-Xian ZHAO ; Xiang-Yu LI ; Fei-Peng PAN ; Dong-Mei XIANG ; Yong LI ;
Chinese Journal of Anesthesiology 1997;0(11):-
Objective To investigate the effects of heart displacement on hemodynamics during off-pump coronary artery bypass grafting (OP-CABG) while the sites for anastomosis were being exposed. Methods Forty-seven patients of both sexes (36 male, 11 female) aged 50-82 years undergoing OP-CABG were enrolled in the study. Preoperative cardiac function was assessed : class Ⅱ in 22 patients; Ⅲ in 23 and Ⅳ in 2 according to NYHA classification.The mean ejection fraction was 0.55?0.14 before surgery.They received on average 3.2 grafts. Premedication consisted of intramuscular morphine 10 mg, midazolam 3-5 mg and scopolamine 0.3 mg.Before induction of anesthesia ECG and SpO2 were monitored and radial artery was cannulated for continuous direct BP monitoring. Anesthesia was induced with midazolam 0.1 nig?kg-1 , fentanyl 4?g?kg-1 and pancuronium 0.1 mg?g-1 iv.The patients were mechanically ventilated after tracheal intubation and PETCO2 was maintained at about 40 mm Hg. Anesthesia was maintained with isoflurane and 50%-60% N2O in O2 and intermittent intravenous boluses of fentanyl and pancuronium. Swan-Ganz catheter which can continuously monitor mixed venous blood O2 saturation (SvO2) was placed in pulmonary artery via right internal jugular vein. SvO2, cardiac output (CO), BP, pulmonary arterial pressure (PAP) and HR were continuously monitored. Right atrial pressure (RAP) and PAWP were measured intermittently. Cardiac index (CI),stroke index (SI),systemic vascular resistance index (SVRI),PVRI, left and right ventricular work index (LVWI,RVWI) and left and right ventricular stroke work index (LVSWI,RVSWI) were calculated. The hemodynamic parameters were recorded after induction of anesthesia before surgery (T1,baseline),before heart displacement (T2), while anastomosis to anterior descending branch was being made (T3), while anastonosis to right coronary artery or posterior descending branch (T4) and to left circumflex artery or diagonal branch (T5) was being made, after normal heart position was resumed (T6) and at the end of operation (T7). Results While anastomosis to the anterior descending branch was being made (T3) SI and LVSWI significantly decreased as compared with the baseline (P
8.Prevalence of metabolic syndrome, its components and hyperuricemia among Kazakh people in Xinjiang Uighur autonomous region
Yalin WEI ; Yitong MA ; Yining YANG ; Zhenyan FU ; Fen LIU ; Xiao PENG ; Xiang XIE ; Xiang MA ; Xiaomei LI ; Ying HUANG
Chinese Journal of General Practitioners 2011;10(7):480-483
Objective To study prevalence of metabolic syndrome (MS) , it's components and hyperuricemia (HUA) among Kazakh people in Xinjiang Uighur autonomous region, China. Methods A cross-sectional survey was conducted among Kazakh people aged 35 years and over in seven prefectures of Xinjiang, including Urumqi, Kelamayi (Karamay) , Fukang, Tulufan (Turpan), Hetian (Hotan) , Aletai (Altay) and Yili during October 2007 to March 2010, with a four-stage cluster sampling, the total sample size were 4094. Through the methods of questionnaire survey, physical examination, biochemical examination and so on, to study prevalence of MS in HUA and it's components by blood biochemical examinations. Results A total of 3915 Kazakh adult people, equal number of men and women, were surveyed, with a response rate of 95. 63 percent. Overall prevalence of HUA was 3. 96 percent( 155/3915 ) , 6.02 percent for men and 2. 03 percent for women(114/1894 and 41/2021) , respectively, with statistically significant difference ( P < 0.05 ). Prevalence of MS was 39.47 percent in those with HUA and 22. 53 percent in those without HUA (45/114 and 401/1780), respectively (P < 0.01). Among women, prevalence of MS was 46. 34 percent in those with HUA and 16. 11 percent in those without HUA( 19/41 and 319/1980), respectively (P<0. 01). Prevalence of high blood pressure, hypertriglyceridemia, lower blood high-density lipoprotein cholesterol (HDL-C) and central obesity were 59.65 percent, 42.11 percent,32.46 percent, 7. 89 percent and 79. 82 percent in those with HUA, respectively, with prevalence of hyperglyceridemia and central obesity significantly higher than in those of non-HUA ( P < 0. 05 ). Among women, prevalence high blood pressure, hypertriglyceridemia, lower blood HDL-C and central obesity were 48.78 percent, 39.02 percent, 41.46 percent, 2.44 percent and 78.05 percent, respectively, in HUA group, with prevalence of hyperglyceridemia, lower blood HDL-cholesterol and central obesity significantly higher than in those of non-HUA ( P < 0. 05 ). Conclusions Prevalence of MS was higher in Kazakh people suffered with HUA than those without HUA, as well as prevalence of components of MS, suggesting that prevention and treatment for HUA is necessary, which can reduce MS and its components in the region.
9.Efficacy and safety of sunitinib in the treatment of metastatic renal cell carcinoma
Shulin CHENG ; Hao ZENG ; Xiang LI ; Peng GUO ; Lin DAI ; Ni CHEN ; Yuchun ZHU ; Peng ZHANG ; Qiang WEI
Chinese Journal of Urology 2010;31(5):304-307
Objective To investigate the efficacy and side effects of the molecular targeted drug sunitinib in the treatment of metastatic renal cell carcinoma(mRCC). Methods Fifteen patients with histopathological confirmed mRCC,including 10 males and 5 females,were enrolled in the study.The median age was 56(range from 37 to 73 years).Fourteen cases of clear-cell RCC and 1 papillary RCC were diagnosed.Thirteen patients had prior nephrectomy,and 6 patients were treated with cytokines previously.All of the patients were given sunitinib at a dosage of either 50 mg daily(4 weeks on/2 weeks off)or 37.5 mg daily continuously.Objective response rate(ORR),progressive-free survival(PFS)and overall survival(OS)were evaluated,and adverse events were also observed. Results The median follow-up was 13 months(2-24 months).According to RECIST,partial response could be evaluated in 8 patients and stable was found in another 5 patients.Only 2 patients were confirmed disease progression.The ORR was 53% with the disease control rate of 87%,However,the median PFS and OS were not yet available due to the short-term follow-up.During the treatment,the most common adverse events experienced by patients were hand-foot syndrome 11/15(73%),changes in hair color 10/15(67%),mucositis 9/15(60%),alopecie 9/15(60%),diarrhea 8/15(53%)and neutropenia 8/15 (53%). All of adverse events were manageable and reversible. Conclusions Sunitinib as a single agent in the treatment for Chinese mRCC patient is efficient and the side effects are reversible. Further long-term follow-up and expanded samples should be expected to confirm the efficacy and safety of sunitinib.
10.Research progress on preparation technology of nanocrystal drugs
Yang TIAN ; Yi-fan PENG ; Zhi-wei ZHANG ; Hui ZHANG ; Xiang GAO
Acta Pharmaceutica Sinica 2021;56(7):1902-1910
Nanocrystal drugs have many advantages, such as no carrier materials, easy industrialization, diversified dosage forms, and can significantly improve the solubility and bioavailability of insoluble drugs, so many drugs have been on the market. The traditional nanocrystal preparation technology has the problems of low preparation efficiency and process limitation of the smallest achievable particle size. With the progress of pharmaceutical preparation technology, the preparation technology of nanocrystal drugs is constantly improving, and new preparation technologies are constantly emerging. The emergence of new technologies has greatly shortened the process time and makes it possible to prepare nanocrystal drugs with smaller particle diameters. In this paper, the preparation technologies of nanocrystal drugs, especially the new preparation technologies such as high gravity controlled precipitation, microfluidic reaction technology and various combination technologies, are reviewed from three aspects: "Top-down" technology, "Bottom-up" technology and combination technology. This article also prospects the development of new preparation technologies, hoping to provide reference for the related research of nano-preparations.