1.The role and mechanisms ofω-3 polyunsaturated fatty acids in inducing cell apoptosis and anti-prolif-eration in multiple myeloma
Yu ZHAO ; Xiaoting ZHU ; Yinan WANG
Practical Oncology Journal 2016;30(6):516-522
Objective To explore the role and mechanisms of ω-3 polyunsaturated fatty acids (ω-3PUFA) alone or in combination with dexamethasone ( DEX) in inducing cell apoptosis and anti -proliferation in multiple myeloma(MM).Methods DEX resistance MM cell line MM1R were treated with different concentra-tions of Eicosapentaenoic acid(EPA)or Docosahexaenoic acid(DHA)alone or in combination with DEX for 24hrs or 48hrs.Cell proliferation was detected by MTT .Cell cycle and apoptosis were measured by flow cytometry .The levels of apoptosis related proteins were analyzed by Western blot .Results The proliferation of MM1R was in-hibited by different concentrations (10,20,50,100μM)of EPA or DHA alone or in combination with 10μM DEX in a dose-and time-dependent manner .Inhibition effect was significantly higher in combinative groups than in single agent groups(P<0.05).The percentage of G0/G1 phase and cell apoptosis rate in MM1R treated with dif-ferent concentrations of EPA or DHA alone was increased in a dose -dependent manner ,and being significantly higher in combinative groups than in single agent groups (P<0.05).The expressive levels of cleaved caspase -3 and Bax were up-regulated ,while pro-caspase-3 and BCL-2 were down-regulated in a dose-dependent manner.Conclusion ω-3PUFA can inhibit DEX resistant MM cell proliferation ,arrest cell cycle and induce cell apoptosis ,and has a synergistic anti -resistant effect in combination with DEX ,may serve as a new ,effective MM drugs.
2.Effects of Tuina on cartilage degradation and chondrocyte terminal differentiation in rats with knee osteoarthritis (KOA) via the Wnt/β-catenin signaling pathway
Yinan YU ; Youhong XIE ; Chenglin TANG ; Xiao GUO
Journal of Acupuncture and Tuina Science 2023;21(1):18-26
Objective: To investigate the therapeutic effects of Tuina (Chinese therapeutic massage) in a knee osteoarthritis (KOA) rat model and its influence on proteins associated with the Wnt/β-catenin signaling pathway. Methods: A total of 32 specific-pathogen-free grade Sprague-Dawley rats were used. Eight rats were randomly selected as the control group (CG). The remaining 24 rats underwent intra-articular injections with 0.2 mL of 4% papain to prepare the KOA rat models. After the model was established, the 24 rats were randomly and equally assigned to 3 groups, including a model group (MG), a Tuina group (TG), and a positive medicine group (PMG), with 8 rats in each group. The Lequesne score was applied to evaluate the success of model development. After the model was successfully established, the CG did not receive any intervention, and the TG was treated with local, clockwise annular Rou-Kneading around the knee joint with the thumbs. The pressure in the longitudinal direction was 3 N, and the frequency was designed to be 120-140 times/min for 15 min, followed by flexing the joint 10 times. The PMG was intragastrically administered with celecoxib [24 mg/(kg·bw)] every day. These interventions were performed once a day, 6 d per week, for a total of 4 weeks. After treatment, the Lequesne score was applied again to assess the severity of the KOA in the rats; hematoxylin-eosin (HE) staining and a mixture of equal volumes of aqueous solutions of safranin O-fast green were used to stain and observe the cartilage morphology and structure; the modified Mankin score was applied to evaluate the pathology; enzyme-linked immunosorbent assay method was used to quantify the C-telopeptide fragments of type Ⅱ collagen (CTX-Ⅱ) and cartilage oligomeric matrix protein (COMP); Western blotting was then applied to quantify Wnt4, β-catenin, matrix metalloproteinase 13 (MMP-13), and bone morphogenetic protein 2 (BMP-2) protein expression; immunohistochemistry was conducted to determine the percentage of collagen type X (ColX)-positive cells. Results: The Lequesne score of the TG and PMG was both lower than that of the MG (P<0.01); the HE staining, safranin O-fast green stained morphology and structure, and modified Mankin scores of the TG and the PMG were also better than those in the MG (P<0.01). Compared with the CG, the amounts of CTX-Ⅱ and COMP in the serum were significantly increased (P<0.01); the expression of Wnt4, β-catenin, MMP-13, and BMP-2 proteins in the cartilage tissue was significantly increased (P<0.01), and the percentage of ColX-positive chondrocytes was significantly increased (P<0.01) in the MG. In comparison with those in the MG, the amounts of CTX-Ⅱ and COMP were significantly decreased (P<0.01), the expression of Wnt4, β-catenin, MMP-13, and BMP-2 proteins was significantly decreased (P<0.01), and the percentage of ColX-positive chondrocytes was significantly decreased (P<0.01) in the TG and PMG. Compared with the PMG, the contents of CTX-Ⅱ and COMP and the expression of Wnt4, β-catenin, MMP-13, and BMP-2 proteins were decreased (P<0.05 or P<0.01); the percentage of ColX-positive chondrocytes was significantly decreased (P<0.01) in the TG. Conclusion: Tuina can relieve the degeneration of KOA, and the mechanism may be related to the down-regulation of the Wnt/β-catenin signaling pathway, the decrease in MMP-13 and BMP-2 protein expression, the reduction in chondrocyte extracellular matrix degradation, and slowing down the terminal cell differentiation.
3.Association study between simple febrile seizures and gabbr1 gene and gabbr2 gene
Yujie LI ; Yinan MA ; Yu QI ; Junyi WANG ; Liping ZOU
Chinese Journal of Applied Clinical Pediatrics 2014;29(12):891-894
Objective To investigate whether the gamma-aminobutyric acid (GABAB) receptor genes,including gabbr1 gene and gabbr2 gene,are the susceptible genes for simple febrile seizures (sFS) by screening mutation of gabbr1 gene and gabbr2 gene and to study the possible association between sFS and the 2 genes.Methods All exons and flanking introns of gabbr1 gene and gabbr2 gene were amplified with polymerase chain reaction (PCR) and sequenced to screen the possible mutation on 60 children with sFS in the northern China in Han nationality population.One hundred and one healthy children from the same area were selected as controls,and the genotypes of single nucleotiole polymorphisms (SNPS) (rs29220,rs29230,rs29267 on gabbr1 gene and rs1000440,rs3205936,rs2304391 on gabbr2 gene) were typed by PCR-restriction fragment length polymorphism.EH1.20 software was used to estimate haplotype frequency to study the association with the haplotype as genetic marker between case group and control group.Results No mutation associated with sFS was found in the 60 sFS cases.In all sequenced regions,23 SNPs were identified in both genes:6 SNPs in gabbr1 gene and 17 SNPs in gabbr2 gene.The frequencies of the 6 SNPs were complied well with the Hardy-weinberg equilibrium in sFS group and normal group.Genotype proportions and allele frequencies of 6 SNPs were not significantly different between both groups.The haplotypes of 3 SNPs in gabbr1 gene and in gabbr2 gene distributions were not significantly different between 2 groups.Conclusions No mutations and associations were identified between sFS with both GABAB receptor genes(gabbr1 gene and gabbr2 gene).They may not be the susceptibility gene for simple febrile seizures in Han nationality population in northern China.
4.Research on relative factors of abnormal glycometabolism in chronic hepatitis C patients
Mei LIU ; Feng ZANG ; Yinan YAO ; Peng HUANG ; Rongbin YU
Chinese Journal of Disease Control & Prevention 2017;21(9):909-912,970
Objective Hepatitis C virus patients are often accompanied by insulin resistance and diabetes.To probe the relative factors of abnormal glycometabolism in chronic HCV infections.Methods A total of 1 039 treatment-naive patients that were confirmed chronic HCV infected were enrolled in the study.The demographics,biochemical index parameters and other data about liver function and HCV viral load were got from infectious disease department of Jurong Pepole's Hospital in China.Results A total of 140 (13.5%) patients were diagnosed with some forms of abnormal glycometabolism.The body mass index (BMI) (x2 =9.231,P =0.010),waist circumference (x2 =7.984,P =0.018),systolic blood pressure (x2 =16.366,P <0.001),diastolic blood pressure (x2 =13.970,P =0.001),alanine aminotransferase(ALT) (x2 =4.809,P =0.028),HCV-RNA viral load (t =-3.818,P <0.001) were significantly different between non-diabetic HCV patients and abnormal glycometabolism patients.Multivariate logistic regression analysis showed that ALT(OR =2.986,95% CI:1.171-7.615) and HCV-RNA viral load (OR =2.061,95% CI:1.165-3.644) were found as risk factors in multivariate regression analysis for patients with chronic hepatitis C who had abnormal glucose metabolism.Conclusions Chronic hepatitis C patients with higher ALT and HCV-RNA level were more probably to suffer from abnormal glycometabolism.In order to find potentially novel risk factors of HCV with abnormal glucose metabolisn,further studies about genetic and other clinical factors need to be processed.
5.Double-blind study of the efficacy and safety of desloratadine for treating allergic rhinitis
Yinan WANG ; Xianli YU ; Changyou JI ; Zhongzhan NI ;
Journal of Third Military Medical University 2003;0(18):-
Objective To evaluate the efficacy and safety of desloratadine for the treatment of allergic rhinitis. Methods A total of 50 cases of chronic or acute allergic rhinitis confirmed clinically were randomized into control and experimental groups for double blind study. Scoring of clinical symptoms, examinations of the nasal cavity, blood and urine routine examination, functions of liver and kidney and electrocardiogram (ECG) were conducted on day 14 before and after the experiment. The collected data were analyzed statistically. Results The clinical data of the two groups were comparable. The effective rate of desloratadine was significant in allergic rhinitis, being 95.45%. No remarkable adverse effect was noted in this experiment. Conclusion Desloratadine is more effective and safe than loratadine in the treatment of allergic rhinitis and it may be feasible for clinical application.
6.Prenatal diagnosis of mitochondrial disease: analysis of 28 pedigrees with mitochondrial DNA mutation
Yu LIU ; Ying ZHANG ; Xuefei ZHENG ; Hong PAN ; Yu QI ; Yinan MA
Chinese Journal of Perinatal Medicine 2017;20(9):679-683
Objective To perform a prenatal diagnosis for the second fetuses from 28 pedigrees with proband of mitochondrial disease due to mitochondrial DNA (mtDNA) mutation.Methods From April 2011 to November 2015,peripheral blood samples of 28 probands and their parents,urine samples of these probands and their mothers as well as amniotic fluid samples of the second fetuses from the 28 pedigrees were collected in Peking University First Hospital.DNA sequencing was used to identify mtDNA mutations.Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to verify mutation sites,calculate mutation loads,and further confirm the diagnosis after birth.Microsatellite maker analysis was also performed on five short tandem repeats located in nuclear genes to exclude maternal contamination.Statistical analysis was carried out using independent t-test.Results In the 15 pedigrees carrying A3243G mutation,13 mothers and nine fetuses carried A3243G mutation.Neither the other two mothers nor their fetuses were positive for A3243G mutation.Among the 12 pedigrees with T8993G mutation,there were eight mothers carrying T8993G mutation and all of their fetuses carried the same mutation;and the other four mothers and their fetuses were negative for T8993G mutation.T10191C mutation was only found in one proband and the second fetus of that pedigree,but not in the mother.None of the fathers had mtDNA mutation.Results of PCR-RFLP were consistent with those of DNA sequencing.Short tandem repeat analysis demonstrated that amniocyte samples were from fetuses without maternal contamination.No mtDNA mutations were found in the six newborns who were negative for mtDNA mutations in prenatal diagnosis.The mean mutation load in urine samples of the six mothers without A3243G mutation in amniocytes was significantly lower than that of the nine mothers with A3243G mutation [(10.1 ±4.8) % vs (28.2 ± 15.1) %,t=2.290,P=0.043].Conclusions The lower the mtDNA mutation load in maternal urine samples,the less the possibility she bears a child with mtDNA mutation.However,prenatal diagnosis of mitochondrial disease is necessary.
7.Correlation of sarcopenia and metabolic risk factors
Yu WANG ; Mingxia JIANG ; Qi XU ; Mengmeng WU ; Yinan ZHOU ; Xinyuan DONG ; Jinfeng ZHENG
Journal of Medical Postgraduates 2017;30(2):181-185
Objective Sarcopenia and metabolic syndrome share similar pathophysiological mechanisms. The aim of this study was to investigate the prevalence of sarcopenia among health examination population, and to analyze the relationship between sar-copenia and blood pressure, blood glucose, uric acid and lipids. Methods Physical examination data of 1191 healthy persons in the medical examination center of the hospital from Mar 2011 to Jun 2011 were collected. The weight, skeletal muscle, body fat, body mass index ( BMI) , waist circumference,body fat percentage, waist-hip ratio and visceral fat area were analyzed by human body compositionanalyzer and the prevalence of sarcopenia was observed. At the same time, triglyceride (TG), total cholesterol (TC), high density lipo-protein-cholesterol ( HDL-C ) , low density lipoprotein-cholesterol ( LDL-C) , uric acid and fasting blood glucose were also detected. Results The prevalence rate of sarcopenia of the subjects was 5.21%, and the highest incidence was found in ≥60 years group( 11.11%) . The prevalence rates of overweight and obesity were 33.8% and 10.2%, respectively. The prevalence of sarcopenia is grad-ually higher along with increasing BMI. The prevalence rates of sarcopenia of overweight and obesity subjects were 5.47% and 26.23%, respectively. Compared with the normal control group, the level of weight[(66.34±11.75)kg vs (76.71±12.84)kg ], BMI[(23.37± 3.13) vs (28.05±3.66)], body fat percentage[(25.33±6.06)% vs (36.76±4.47)%], waist circumference[(83.19±9.56)cm vs (95.45±13.74)cm] and visceral fat area[(88.96±29.74)cm2 vs (136.91±25.56)cm2] were higher in the sarcopenia group (P<0.05). Compared with the normal control group, the incidence of systolic blood pressure[(125.59±30.04)mmHg vs (139.39±19.79) mmHg], diastolic blood pressure[(75.82±11.95)mmHg vs (82.34±10.96)mmHg ] TG[(1.56±1.12)mmol/L vs (1.98±1.72)mmol/L] and uric acid[(313.75±83.07)mmol/L vs (335.55±96.07)mmol/L] were higher in the sarcopenia group (P<0.05). Compared with the normal subjects, the detectable rates of abnormal diastolic blood pressure, fasting blood glucose, uric acid, and LDL-C were increased in the sarcopenia, obesity and sarcopenia combined with obesity subjects (P<0.05). The odds ratio of abnormal systolic blood pressure, diastolic blood pressure, uric acid, and LDL-C increased in the sarcopenia, obesity and sarcopenia combined with obe-sity subjects using logistic regression analyses after correction of gender and age. Conclusion The sarcopenia may have some con-nection with metabolic risk factors. Early detection of sarcopenia can help to distinguish people predisposed to metabolic syndrome, and it has important significance for prevention of chronic disease.
8.Prenatal diagnosis of monogenic global developmental delay/intellectual disability in 43 pedigrees
Liling LIN ; Ying ZHANG ; Hairong WU ; Hong PAN ; Jingmin WANG ; Yinan MA ; Yu QI
Chinese Journal of Perinatal Medicine 2021;24(1):20-27
Objective:To summarize the prenatal diagnostic characteristics of monogenic global developmental delay/intellectual disability(GDD/ID) pedigrees.Methods:This study retrospectively collected the prenatal molecular diagnostic results of 43 pedigrees that were affected with monogenic GDD/ID in the genetic counseling clinic of Peking University First Hospital from January 2015 to June 2019. The results of prenatal molecular tests were validated after birth or pregnancy termination. Pregnancy outcomes and healthy condition of the offspring were followed up. All data were analyzed by descriptive statistical analysis.Results:Among the 43 pedigrees, 24 were affected with autosomal recessive inheritance (AR) GDD/ID, in which six (25%) fetuses were found to carry two pathogenic variants; 13 (55%) had only one pathogenic variant; five (20%) did not harbor any variant. GDD/ID inherited in an autosomal dominant inheritance (AD) pattern was found in 13 pedigrees, in which 11 fetuses carried no variants while the other two fetuses had the same variants as the proband had (in one pedigree, a low-level variant was detected in the peripheral blood sample of the father while absent in peripheral blood samples of parents in the other pedigree, so it was suspected that the variants of these two affected fetuses were inherited from parental mosaicism). In the other six pedigrees with X-linked inheritance (XL) of GDD/ID, one male fetus was found to harbor the pathogenic variant, while no variants were detected in the others. Maternal contamination was excluded in all prenatal samples using short tandem repeat for linkage analysis. Postnatal validations were consistent with the prenatal tests. All nine affected fetuses were terminated, and the other thirty-four children were delivered and in good health.Conclusions:Prenatal molecular diagnostic test is an effective method to detect pathogenic variants during the first and second trimesters for pedigrees affected by monogenic GDD/ID. For pedigrees affected with AD or XL patterns caused by de novo mutations, potential parental mosaicism should be noted and prenatal diagnostic tests are also recommended.
9.Effect of HbA1c meeting the standard or not on microalbuminuria,blood lipids and liver enzymes in patients with type 2 diabetes
Keying ZHANG ; Peng CAO ; Jian DU ; Yinan YU ; Yun LI ; Hongfei LUO
Journal of Chinese Physician 2011;13(2):167-169
Objective To investigate the effect of HbA1c meeting the standard or not on microalbuminuria,blood lipids and liver enzymes in patients with type 2 diabetes.Methods A retrospective analysis was performed on 457 subjects who had type 2 diabetes.They were divided into substandard group and standard group according to HbA1c result.The general information and relevant laboratory indicators of patients were.collected and compared between two groups.Results The microalbuminuria,serum triglyceride and liver enzymes (glutamyl transpeptidase,alkaline phosphatase,aspertate aminotransferase) were significantly different between two groups [ (189.8 ± 235.3) mg/dl vs (38.9 ± 85.5) mg/dl,(2.64 ± 2.99) mmol/L vs (2.02 ± 1.50)mmol/L,(41.7 ±52.9)U/L vs (29.7 ±24.9)U/L,(83.6 ±28.6) U/L vs (74.3 ±25.8)U/L,(26.7 ±19.1)U/L vs (22.0 ±10.5) U/L,P <0.05].HbA1c level was positively correlated with microalbuminuria,glutamyl transpeptidase and alkaline phosphatase (r =0.209,0.115,0.11,P <0.01).The microalbuminuria was an independent risk factor of affecting HbA1c to reach the standard (OR = 1.009,P <0.05).Conclusions HbA1c meeting the standard or not can influence many factors except blood glucose.
10.Application of enteral nutrition and parenteral nutrition support in critically ill surgical patients.
Min WU ; Tieou YU ; Yinan LI ; Ping KANG ; Bin FANG ; Weibiao WEN
Chinese Journal of Practical Surgery 2001;21(4):213-215
Objectives To evaluate the effects of enteral nutrition(EN)and parenteral nutrition(PN)support in critically ill surgical patients. Methods 80 patients who could not eat were randomized into two groups:one group receivedEN,the other group received PN. The nutrition parameters including nitrogen balance, serum levels of albumin, prealbumin, transferrin and retinal-binding protein,immunity function parameters including immunoglobulin A, immunoglobulin G,immunoglobulin M,and natural kill cell activity, and patients'tolerability parameters including glutamic-oxalacetic transaminase, glutarmic-pyruvic transaminase, blood urea nitrogen and creatinine,and plasma glucose were compared. Results After 10 days'therapy,the two groups all turned from negative nitrogen balance to positive nitrogen balance. The nutrition parameters and immunity function parameters increased significantly in both groups and the latter in group EN increased more. For tolerability parameters, blood sugar in group PN increased obviously and no change in EN group. ConclusionsBoth EN and PN play a rde in nutrition support and elevation of immunity function. Patients tolerate well. EN has better effects on elevation of immunity function and patients tolerate better compared with PN.