1.Human umbilical cord mesenchymal stem cells attenuate diabetic nephropathy through the IGF1R-CHK2-p53 signalling axis in male rats with type 2 diabetes mellitus
ZHANG HAO ; WANG XINSHU ; HU BO ; LI PEICHENG ; ABUDUAINI YIERFAN ; ZHAO HONGMEI ; JIEENSIHAN AYINAER ; CHEN XISHUANG ; WANG SHIYU ; GUO NUOJIN ; YUAN JIAN ; LI YUNHUI ; LI LEI ; YANG YUNTONG ; LIU ZHONGMIN ; TANG ZHAOSHENG ; WANG HUA
Journal of Zhejiang University. Science. B 2024;25(7):568-580,中插1-中插3
Diabetes mellitus(DM)is a disease syndrome characterized by chronic hyperglycaemia.A long-term high-glucose environment leads to reactive oxygen species(ROS)production and nuclear DNA damage.Human umbilical cord mesenchymal stem cell(HUcMSC)infusion induces significant antidiabetic effects in type 2 diabetes mellitus(T2DM)rats.Insulin-like growth factor 1(IGF1)receptor(IGF1R)is important in promoting glucose metabolism in diabetes;however,the mechanism by which HUcMSC can treat diabetes through IGF1R and DNA damage repair remains unclear.In this study,a DM rat model was induced with high-fat diet feeding and streptozotocin(STZ)administration and rats were infused four times with HUcMSC.Blood glucose,interleukin-6(IL-6),IL-10,glomerular basement membrane,and renal function were examined.Proteins that interacted with IGF1R were determined through coimmunoprecipitation assays.The expression of IGF1R,phosphorylated checkpoint kinase 2(p-CHK2),and phosphorylated protein 53(p-p53)was examined using immunohistochemistry(IHC)and western blot analysis.Enzyme-linked immunosorbent assay(ELISA)was used to determine the serum levels of 8-hydroxydeoxyguanosine(8-OHdG).Flow cytometry experiments were used to detect the surface markers of HUcMSC.The identification of the morphology and phenotype of HUcMSC was performed by way of oil red"O"staining and Alizarin red staining.DM rats exhibited abnormal blood glucose and IL-6/10 levels and renal function changes in the glomerular basement membrane,increased the expression of IGF1 and IGF1R.IGF1R interacted with CHK2,and the expression of p-CHK2 was significantly decreased in IGF1R-knockdown cells.When cisplatin was used to induce DNA damage,the expression of p-CHK2 was higher than that in the IGF1R-knockdown group without cisplatin treatment.HUcMSC infusion ameliorated abnormalities and preserved kidney structure and function in DM rats.The expression of IGF1,IGF1R,p-CHK2,and p-p53,and the level of 8-OHdG in the DM group increased significantly compared with those in the control group,and decreased after HUcMSC treatment.Our results suggested that IGF1R could interact with CHK2 and mediate DNA damage.HUcMSC infusion protected against kidney injury in DM rats.The underlying mechanisms may include HUcMSC-mediated enhancement of diabetes treatment via the IGF1R-CHK2-p53 signalling pathway.
2.Changes in clinical indicators among human immunodeficiency virus patients who failed in antiretroviral therapy during 2004-2016 in Yunnan, China: an observational cohort study
Peicheng WANG ; Junfang XU ; Bingbing GUO ; K-Jason WANG ; Liangmin GAO ; Qianyun WANG ; Jun JING ; Feng CHENG
Global Health Journal 2020;4(2):57-63
Background:This study aimed to investigate the changes in the clinical indicators and influencing factors of treatment duration among human immunodeficiency virus (HIV) patients in whom antiretroviral therapy (ART) was unsuccessful.Methods:In this retrospective study,a total of 9,418 HIV patients who failed in ART during 2004-2016 were included and divided into two treatment groups-Group 1 (treatment time ≤ 3 years,n1 =5,218) and Group 2 (treatment time > 3 years,n2 =4,200).Patient follow-up data,including age,cluster of differentiation 4 (CD4) count,and viral load,glucose,creatinine,and triglyceride levels,were extracted from electronic health record databases.Covariance analysis for repeated measures was used to analyze the biochemical indicators,and multiple logistic regression modeling was used to compare relevant data extracted from the Group 1 and Group 2 HIV patient cohorts with different treatment time.Results:The median initial CD4 count was 175.0 cells/μl (interquartile range,77.0-282.0),while the initial CD4 counts for Group 1 were lower than those for Group 2 (P < 0.05).A significant interaction between group and time effects was observed (P < 0.05) in total cholesterol (TC).Changes in hemoglobin level among HIV patients were also significantly associated with treatment time (P =0.001).The initial CD4 count (odds ratio [OR] =0.756),female sex (OR =0.713),Zerit (d4T) (OR =1.443),TC (OR =1.285),and aspartate aminotransferase level (OR =1.002) were significantly associated with the survival time of dead patients with HIV (P < 0.05).Additionally,the initial CD4 count (OR =1.456),age (OR =1.022),time interval (OR =0.903),patient's living status (OR =0.597),d4T (OR =2.256),and triglyceride (OR =0.930) and hemoglobin levels (OR =0.997) were significantly associated with the treatment time of HIV patients with drug withdrawal (P < 0.05).Conclusion:The initial biochemical parameters can affect the survival and treatment time of HIV patients.With a comprehensive understanding of the physiological and biochemical indicators of patients,we can reduce the probability of drug withdrawal and prolong the survival time of HIV patients.
3.Comparison of different methods for measuring the phenylalanine concentration of phenylketonuria patients in dried blood spots
Xia ZHAN ; Wenjuan QIU ; Peicheng WANG ; Feng XU ; Peizhong BAO ; Xiaolan GAO ; Jun YE ; Xuefan GU
Chinese Journal of Laboratory Medicine 2018;41(5):361-365
Objective To compare the phenylalanine(Phe)concentration in the sample of dried blood spot,measured by four different methods:fluorescence assay,tandem mass spectrometry(MS/MS), including MS/MS Derivatized,MS/MS Non-Derivatized and MS/MS-Standard Curve.Methods A total of 204 dried blood spot(DBS)samples of phenylketonuria(PKU)patients from Shanghai Xinhua Hospital were collected in this study.Phe concentration in DBS was measured by fluorescence assay and MS /MS assay,including MS/MS Derivatized, MS/MS Non-Derivatized and MS/MS-Standard Curve.The samples were divided into low, middle and high concentration groups according to Phe concentration, which were under the 360 μmol/L,between 360 and 600 μmol/L,and over 600 μmol/L respectively.The differences among the groups were analyzed by consistency check and non-parametric test.Results The within-day and between-day precisions of MS/MS-Standard Curve assay were 4.0%-7.2%,the recoveries were 93.2%-97.3%.Consistency check showed that less than 8.1%of Phe value were out of the 95%limit of agreement among these four methods.In the low and middle concentration groups,the quartile of Phe value measured by fluorescence assay,MS/MS Standard Curve and MS/MS Derivatized were 176(118,251)μmol/L,174 (94,273)μmol/L,153(94,242)μmol/L; and 540(478,578)μmol/L,485(414,529)μmol/L,466(402,513)μmol/L,respectively.Phe value measured by fluorescence assay was significantly higher than that by MS/MS Standard Curve,the difference was 4.8%-9.0%,(Z=-3.787 to -2.674,P<0.01). Phe value obtained from MS/MS Non-Derivatized was less than that by MS/MS-Standard Curve, the difference was 3.9%-5.2%,(Z=-7.474 to -5.747,P<0.01).In the high concentration group,the quartile of Phe value measured by MS/MS-Standard Curve, MS/MS Derivatized, MS/MS Non-Derivatized and fluorescence assay were 807(695,924)μmol/L,700(575,785)μmol/L,680(623,771)μmol/L and 711(674, 794)μmol/L, respectively.Phe value obtained from MS/MS Standard Curve was significantly higher than those from the other methods and the difference was 10.9% -16.2%,(Z=-4.458 to-4.356,P<0.01).Conclusions The MS/MS Standard Curve assay showed good specificity and accuracy.These four assays displayed good agreement.Although there was difference in measuring the Phe concentration among these methods, they could be used in blood Phe concentration monitoring for PKU patients.
4.Quantitative and Structural Analysis of Professionals in the Institutions Affillated to System of China Disabled Persons' Federation
Qi JING ; Zhouying QIU ; Lihong JI ; Guiding MA ; Wei LI ; Peicheng WANG ; Hong SHENG ; Wengui ZHENG ; Anning MA ; Anqiao LI ; Boyuan CHEN
Chinese Journal of Rehabilitation Theory and Practice 2018;24(8):975-979
Objective To analyze the status, trends and issues of professionals in rehabilitation institutions in China, and provide policy recommendations on rehabilitation professional development.Methods The data from database and statistical bulletin of CDPF has been analyzed using descriptive analysis and deviation analysis.Results The quantity of professionals of rehabilitation institutions increased 24,900 (12.62%) in 2016. Average professionals per institution had been decreased from 33.89 in 2012 to 28.33 in 2016. In regard to the structure of distribution, the rehabilitation professionals at provincial level had been decreased 21.95% in 2015 than that of in 2012. Both training programs and the number of trainees from rehabilitation institutions had decreased.Conclusion There were big gap between services provision and needs of professionals. The distribution of professionals at provincial, city and county level was under optimization. The on-job training for rehabilitation professionals should be improved. It is recommendated to develop national plan for professionals development to meet the needs of rehabilitation services, advance the on-job training for professionals, develop the higher education of rehabilitation and improve attractiveness of rehabilitation to retain and recruit more professionals.
5.Antiretroviral regimen change among people infected with HIV: evidence from a cross-sectional study in China
Junfang XU ; Peicheng WANG ; Liangmin GAO ; Xinyu PENG ; Feng CHENG
Global Health Journal 2018;2(3):21-30
Background: The rate of death among people living with HIV/AIDS has decreased significantly as a result of treatment with highly active antiretroviral therapy (HAART). However, the issues of drug induced toxicities and complexity of current HAART regimens has remained of great concern. The aim of this study was to determine factors influencing antiretroviral regimen changes among people living with HIV/AIDS in China. Methods: This retrospective study collected data through face-to-face interviews with people living with HIV/AIDS who were receiving HAART, and gathered relevant information from infectious disease hospitals. The following information were collected: social-demographic characteristics, antiretroviral therapies, CD4 cell counts, virus loads, reasons for changing medication and other related data. Mean and percentages were used to describe the frequency of regimen change among patients, and binary logistic regression was employed to test the factors influencing regimen change. Results: 1,123 people who had experienced regimen change were included in the analysis. On average, patients remained on HAART for 10.2 months before changing regimen, and the average CD4 cell count and viral load (VL) were 383.1 cells/μl and 28,132.4 copies/mL respectively when changing regimen. The reasons for modification were determined as treatment failure (52.5%), adverse reactions (32.3%), and other reasons including pregnancy (15.2%). There are significant differences in regimen change among people with different genders (P<0.001), modes of transmission (P<0.001), duration of HAART (P<0.001) and initial CD4 cell counts (P=0.0024). Males, drug users, people taking long-term medication, and those with lower initial CD4 counts when starting HAART tend to change regimen. Conclusion: Treatment failure was the main reason for the change of HAART regimen. Males, drug users, people on long-term medication and those with lower initial CD4 cell counts when starting HAART were most likely to change regimen.
6.Nine compounds from the root bark ofand their anti-inflammatory activitieslammatory activitiesretain-->.
Yanan YANG ; Yawen AN ; Wei WANG ; Ning DU ; Jinghua ZHANG ; Ziming FENG ; Jianshuang JIANG ; Peicheng ZHANG
Acta Pharmaceutica Sinica B 2017;7(4):491-495
Two new compounds, named lyciumlignan D () and lyciumphenyl propanoid A (), along with seven known compounds, were isolated from the root bark of. Their structures were elucidated using spectroscopic data (UV, IR, HR-ESI-MS, 1D and 2D NMR, CD), as well as by comparison with those of the literature. Compounds-were isolated from this genus for the first time. In theassay, compounds,, andexhibited stronger anti-inflammatory effects than the positive control curcumin at a concentration of 10 μmol/L.
7.Detection of Related Substances and Preliminary Study on the Degradation Mechanism of Baicalein
Weijue WANG ; Wujun DONG ; Peicheng ZHANG ; Qianqian SU ; Ruhan FAN ; Yuling LIU
China Pharmacy 2017;28(6):803-808
OBJECTIVE:To establish a method for the separation and detection of related substances in baicalein,identify its structure and preliminarily explore the degradation mechanism. METHODS:HPLC was adopted to detect the baicalein,related impurities and forced destruction of degradation products in synthesis process:the column was ES Industries? FluoroSep-RP Phenyl with mobile phase of 0.3%formic acid-methanol-acetonitrile(gradient elution)at a flow rate of 1.0 mL/min,the detection wavelength was 275 nm,the column temperature was 10℃,and the injection volume was 10μL. LC-MS/MS was conducted to identify the related substances and conjecture degradation mechanism:the column was ES Industries? FluoroSep-RP Phenyl with mobile phase of 0.3%formic acid- methanol (gradient elution)at a flow rate of 1.0 mL/min,the detection wavelength was 275 nm,column temperature was 10℃,and the injection volume was 10μL;ion source was electrospray ion source,positive and negative ions,nebulizer pressure was 55 psi and the drying gas flow was 11 L/min,drying gas temperature was 350℃,capillary voltage was 4.0 kV,detection modes were full-scan first-order MS and selective ion full-scan second-order MS,scan ranges were m/z 100-1000 (first-order MS) and 50-500(second-order MS),ionization voltage was 80-135 eV,and the collision energy was 10-30 eV. RESULTS:The linear range of baicalein was 2.4-480μg/mL(r=0.9999);RSDs of precision,stability and reproducibility tests were lower than 2.0%;the limit of quantitation was 7.2 ng,the limit of detection was 2.4 ng. Baicalein was well separated with related substance and 3 major degradation products,the related substance was chemical synthesis precursor wood butterfly;the degradation products were 6,7-quinone derivatives and 7,8-quinone derivatives,which were isomers;oxidative degradation products were benzoic acid phenyl ester derivatives. CONCLUSIONS:The main mechanisms of alkali degradation and oxidative degradation of baicalein include pyran, reciprocal rearrangement and oxidation reaction;the established method is specific and sensitive,and can be used for the detection of related substances in baicalein.
8.Efficacy Analysis of Root Canal Therapy for Periapical Periodontitis of Maxillary Primary Incisors ;Accompanied by Crown Defects
Ying WANG ; Hongru SU ; Peicheng XU
Chinese Journal of Clinical Medicine 2016;23(1):98-99
Objective:To investigate the efficacy of root canal therapy for periapical periodontitis of maxillary primary incisors accompanied by crown defects .Methods :A total of 114 children patients with periapical periodontitis of maxillary primary incisors (162) accompanied by crown defects ,who were admitted for root canal therapy during January 2010 and December 2012 ,were allocated into the caries group (85 incisors) and the trauma group(77 incisors)according to whether they had trauma history or not .Among them ,there were 75 incisors from 2‐3 years group and 87 incisors from 3‐4 years group .The efficacy analysis were conducted after one year root canal therapy with Vitapex calcium hydroxide paste from J .Morita Corporation . Results :The total cure rate was 62 .35% during one year follow‐up .The cure rate in trauma group was lower than that in the caries group ,and the difference was statistically significant (P<0 .01) .The cure rate of 2‐3 years group was lower than that of 3‐4 years group ,and the difference was statistically significant (P<0 .05) .There was no significant difference regarding cure rate among children with different genders or mobility degrees ,as well as with or without sinus(P>0 .05) .Conclusions :The long term efficacy of root canal therapy for periapical periodontitis of maxillary primary incisors with traumatic history is inferior to that for periapical periodontitis of maxillary primary incisors caused by caries .
9.Expression changes of miRNAs in cerebral ischemia-reperfusion injury after deep hypothermic low flow in mice
Changfeng FAN ; Peicheng DING ; Weiyan ZHANG ; Zhongyuan WEN ; Di YU ; Song WANG ; Xuming MO
International Journal of Cerebrovascular Diseases 2015;(5):354-358
Objective To observe the expression changes of 12 ischemia-related microRNAs (miRNA) in cerebral ischemia-reperfusion injury after deep hypothermic low flow (DHLF) in mice.Methods A total of 80 3-w eek-old healthy and clean grade C57BL/6 male mice w ere randomly divided into either a DHLF model group or a sham operation group. Each group w as redivided into 4 subgroups according to the time points of 2, 6, 12, and 24 h (10 in each group). The bilateral carotid arteries of the DHLF model group w ere clipped and a DHLF model w as established, w hile the carotid arteries of the sham operation group w ere not clipped. The mice w ere sacrified at each time point and the brain tissue w as removed. The total RNA w as extracted. Quantitative reverse transcriptase polymerase chain reaction w as used to detect miRNA expression. Results Compared w ith the sham operation group, the expression levels of 9 miRNAs w ere upregulated, 2 w ere dow n-regulated, and 1 did not have any significant change in the DHLF model group. Conclusions The expression levels of 11 miRNAs changed significantly after DHLF. It might have a regulatory role in cerebral ischemia-reperfusion injury after DHLF.
10.Risk factors for rupture of intracranial aneurysm
Chengdong WANG ; Peicheng CAO ; Daokui WANG
Chinese Journal of General Practitioners 2015;14(5):358-361
Objective To investigate the risk factors of rupture of intracranial aneurysms.Methods Two hundred and seventy eight patients with cerebral aneurysms admitted from January 2000 to December 2013 were enrolled in study,including 122 cases with ruptured intracranial aneurysm (rupture group) and 156 cases without rupture (non-rupture group).The clinical data were collected from two groups,risk factors of aneurysm rupture were studied by univariate analysis and multivariate logistic regression analysis.Results The rates of female gender,smoking history,hypertension and atherosclerosis in rupture group were significantly higher than those in non-rupture group [70.5% (86/122) vs.59.0% (92/156),42.6% (52/122) vs.29.5% (46/156),63.9% (78/122) vs.51.9% (81/156) and 69.7% (85/122) vs.51.3% (80/156);x2 =3.943,5.175,4.034 and 4.319,respectively,all P < 0.05];the width of aneurysm neck and diameter of aneurysm in rupture group were significantly lower than those in non-rupture group (all P < 0.05).In addition,the rates of aneurysm rupture in patients with aneurysm diameter of < 5 mm,5-8 mm and >8 mm were 63.4% (64/101),40.9% (38/93),25.0% (20/84),respectively,Z =27.180,P =0.000;the rates of aneurysm rupture in patients with aneurysm neck width of <4 mm was higher than that with width ≥ 4 mm [67.3% (66/98) vs.31.1% (56/180),x2 =33.832,P =0.000].Multivariate logistic regression analysis showed that aneurysm diameter is an independent risk factor for rupture of intracranial aneurysm (OR =3.759,95CI:1.638-6.879,P =0.001).Conclusions The diameter of intracranial aneurysm in an independent risk factor for aneurysm rupture.Female gender,history of smoking,underlying hypertension and atherosclerosis,and the width of aneurysm neck may also related to the rupture of intracranial aneurysms.

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