2.Regulation of Hepatitis C Virus Replication and Gene Expression by the MAPK-ERK Pathway
Rongjuan PEI ; Xiaoyong ZHANG ; Song XU ; Zhongji MENG ; Michael ROGGENDORF ; Mengji LU ; Xinwen CHEN
Virologica Sinica 2012;27(5):278-285
The mitogen activated protein kinases-extracellular signal regulated kinases (MAPK-ERK) pathway is involved in regulation of multiple cellular processes including the cell cycle.In the present study using a Huh7 cell line Con1 with an HCV replicon,we have shown that the MAPK-ERK pathway plays a significant role in the modulation of HCV replication and protein expression and might influence IFN-α signalling.Epithelial growth factor (EGF) was able to stimulate ERK activation and decreased HCV RNA load while a MAPK-ERK pathway inhibitor U0126 led to an elevated HCV RNA load and higher NS5A protein amounts in Con1 cells.It could be further demonstrated that the inhibition of the MAPK-ERK pathway facilitated the translation directed by the HCV internal ribosome entry site.Consistently,a U0126 treatment enhanced activity of the HCV reporter replicon in transient transfection assays.Thus,the MAPK-ERK pathway plays an important role in the regulation of HCV gene expression and replication.In addition,cyclin-dependent kinases (CDKs) downstream of ERK may also be involved in the modulation of HCV replication since roscovitine,an inhibitor of CDKs had a similar effect to that of U0126.Modulation of the cell cycle progression by cell cycle inhibitor or RNAi resulted consistently in changes of HCV RNA levels.Further,the replication of HCV replicon in Conl cells was inhibited by IFN-α.The inhibitory effect of IFN-α could be partly reversed by pre-incubation of Con-1 cells with inhibitors of the MAPK-ERK pathway and CDKs.It could be shown that the MAPK-ERK inhibitors are able to partially modulate the expression of interferon-stimulated genes.
3.Pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension-operative experience in UCSD
Song GU ; Yan LIU ; Pixiong SU ; Zhenguo ZHAI ; Yuanhua YANG ; Chen WANG ; M.madani MICHAEL ; W.jamieson STUART
Chinese Journal of Thoracic and Cardiovascular Surgery 2010;26(4):232-235
Objective Background Pulmonary endarterectomy (PEA) is a safe and effective surgical treatment for chronic thromboembolic pulmonary hypertension. University of California at San Diego Medical Center is widely recognized as the world's leading referral center for PEA surgery with extensive surgical experience, which has surgically treated about 2400 patients till 2009, which account for more than 50% of the total cases in the world. Methods During visiting in UCSD, 32 pulmonary endarterectomy operations were performed by Prof. Stuart W Jamieson and Mechel M Madani. In these patients, 17 were males (53%), the average age was (47.56 ± 16.04 ) years, 47% with prior history of pulmonary embolism and/or deep vein thrombosis. Obvious pulmonary hypertension and hypoxemia were observed in all patients. Bilateral pulmonary endarterectomy was performed under cardiopulmonary bypass with profound hypothermic circulatory arrest. Results According to the classification of surgical specimens, 21.8% are type Ⅰ , 28.1% are type Ⅱ and 37.5% are type Ⅲ. The average time of cardiopulmonary bypass (CPB) was (236.32 ± 37.27) mins. The aortic cross clamp time was ( 111.69 ± 28.14) mins. The circulatory arrest time was (38.00±13.58 ) mins [ right side (21.39 ± 9.57 ) mins and left side ( 16.61 ± 6.83) mins]. Postoperatively the average mechanical ventilation time was ( 66.23 ± 99.24) hours, and the ICU stay was (4.62 ± 4.50 ) days.There was no postoperative moorality. All cases had significant decrease in systolic pulmonary artery pressure [(81.03 ± 16.92)mm Hg vs. (51.20±12.16) mm Hg] and pulmonary vascular resistance [(88.91 ±42.32) kPa · s · L-1 vs. (34.38 ±15.68 ) kPa · s · L-1 ], great improvement in cardiac output [(3.65 ±1.08 ) L/min vs. ( 5.85 ± 1.21 ) L/min ] and central venous pressure [(13.07 ± 2.11) cmH2O vs. ( 9.86 ± 3.02 ) cmH2O] postoperatively compared to preoperative data. Shortterm follow-up showed that the cardiac function of all cases returned to NYHA class Ⅰ or Ⅱ, with great improvement in CTPA.Conclusion PEA is definitive treatment of chronic thromboembolic pulmonary hypertension. According the successful experience of UCSD PEA team, first and foremost pulmonary endarterectomy is a bilateral procedure, because chronic thromboembolic pulmonary hypertension is mostly a bilateral disease. Second, cardiopulmonary bypass with the aid of deep hypothermia and circulatory arrest are essential to operator in recognizing the true endarterectomy plane of the media and in following the specimen to its feathered tail end in each branch, using these approaches can effectively reduce pulmonary hypertension and provide good hemodynamic and symptomatic results. Third, PEA remains an uncommon procedure in China. Only a few centers can perform high qualified PEA surgery. In most of inexperienced centers, type Ⅰ and type Ⅱ disease should be choose to operation.Patients with sPAP ≥100 mm Hg, PVR ≥ 100 kPa · s · L-1 or type Ⅲ disease will face more dangers peri-operation.
4.Effect of 17β-estradiol on proliferation of human thyroid stem cells
Shuhang XU ; Guofang CHEN ; Quanxi ZHENG ; Xiaodong MAO ; Xuqin ZHENG ; Derwahl MICHAEL ; Chao LIU
Chinese Journal of Endocrinology and Metabolism 2014;30(9):769-774
Objective To investigate the effect of 17β-estradiol on the proliferation of thyroid stem/ progenitor cells.Methods In thyroid stem/progenitor cells derived from nodular goiters,the effects of 17 β-estradiol on thyrosphere formation,estrogen receptor (ER) expression,cyclin D1 expression,and mitogen activated protein kinase (MPAK) pathway were analysed by BrdU ELISA,conventional and realtime PCR,immunofluorensence staining,and Western blot.Results 17β-estradiol induced thyrosphere formation and proliferation of thyroid stem/ progenitor cells.ER-α and ER-β were expressed in thyroid stem and progenitor cells with higher mRNA expression level of ER-α compared to differentiated thyrocytes (8.85-±0.81 vs 1.10 ±0.35,P<0.01).Stimulation by 1 mmol/L 17β-estradiol increased cyclin D1 mRNA expression and ERK phosphorylation levels,which was blocked by an ER antagonist,ICI 182780.Conclusion Estrogen stimulated the growth of stem cells derived from thyroid nodules via estrogen receptor,suggesting the relevance of increased thyroid stem cell proliferation with higher prevalence of thyroid nodules in women.
5.Is imaging the left main able to rule out severe LAD stenosis?
Junbo GE ; Juying QIAN ; Lei GE ; Helge SIMON ; Dietrich BAUMGART ; Michael HAUDE ; Raimumd ERBEL ; Haozhu CHEN
Journal of Geriatric Cardiology 2004;1(1):35-39
Background The 5-year cardiac mortality rate has been reported to be more than 50% in patients with left main coronary artery (LMCA) stenosis. The purpose of this study was to visualize the LMCA using intravascular ultrasound in patients who undergo interventions of the left anterior descending coronary artery (LAD). This was done in order to see the incidence and severity of plaque formation in the LMCA in patients with severe lAD stenosis, and to address if scanning LMCA is able to rule out lAD significant stenosis or vice versa. Methods A total of 293 patients with intervention of the LAD stenosis were examined with intravascular ultrasound(IVUS). The images of 278 patients were suitable for analysis. Results Fifty-three (19%) were found to have angiographic lumen reduction in the LMCA ranging from 11% to 35% (19 ± 8%). Sixty-one patients were found to have native calcification in the LMCA. Atherosclerotic plaques in LMCA were detected in 211/278 (76%) patients, of which 164/211 (78%) were eccentric, and 51/211 (24%) had calcium deposit. The cross-sectional plaque area ranged from 1.5 mm2 to 21 mm2 (8.4 ± 4.7 mm2 ). Area of stenosis was 34 ± 14 % (8-66 % ) and diameter of stenosis was 21 ± 8% ( 7-42% ). A weak relationship concerning severity of stenosis between LAD stenosis and LMCA stenosis was found in the 59 patients with pre-interventional IVUS examinations ( r = 0.47, P < 0.05 ). Condusions LMCA is frequently involved with atherosclerotic lesions in patients with severe LAD stenosis. A weak relationship does exist concerning the severity of stenosis between lAD and LMCA. However, IVUS for LMCA lesion is not able to rule out LAD stenosis.
6.Child sexual abuse: a study among 892 female students of a medical school.
Jing-qi CHEN ; Ping HAN ; Michael P DUNNE
Chinese Journal of Pediatrics 2004;42(1):39-43
OBJECTIVEThis study was designed to ascertain the prevalence of child sexual abuse (CSA) among female students of a medical school and to explore the impact of CSA on the mental health and health related risk behaviors of the victims being sexually abused and to provide useful reference for CSA prevention.
METHODSA cross-sectional survey was carried out among 892 female students from a medical school by anonymous self-administered questionnaire during Oct. 2002. The questionnaire used for this study mainly included (1) general demographic information; (2) sexual experiences; (3) 12 forms of CSA. In this study, cases of CSA were defined as those who answered positively to one or more of the 12 questions relating to childhood sexual experiences (including non-physical contact CSA and physical contact CSA) occurring before age 16 with a person when a child did not want to. (4) Center for Epidemiologic Studies (CES)-Depression Scale; (5) Self Esteem Scale; (6) Risk Behaviors; (7) Health status' self-evaluation. Survey procedures were designed to protect students' privacy by allowing anonymous and voluntary participation. Students were seated separately, completed the self-administered questionnaire in their classrooms during a regular class period. Respondents were encouraged to participate in this survey, but given the sensitive nature of the subject, they could skip portion of the questionnaire if they were not comfortable with the questions. The completed questionnaires were sealed in envelopes by students themselves (the envelope was distributed with questionnaire at the same time), and then collected together. Data were analysed by using the Statistical Package for the Social Sciences software. Frequency, percentage, Chi-square test and t-test of statistics were used to analyze the CSA prevalence and explore the influence of CSA on mental health of students.
RESULTSAmong 892 female students, 25.6% reported having experienced CSA (any one of 12 forms non-physical contact and physical contact CSA) before the age of 16 years. The median age at first episode was 12 years. Comparing the rates of CSA of female students in different parents' education level, between one-child in a family and more than one-child in a family, among rural area, county and city, there were no significant differences. Compared to the students who had not experienced CSA, the students who had experienced CSA reported higher levels of depression (CES-D score 18.78 vs. 16.68, t = 2.81, P = 0.005), lower levels of health status self-evaluation (score 3.53 vs. 3.78, t = 2.94, P = 0.003); higher proportion of subjects who reported drinking alcohol and having ever smoked during the past 30 days (drinking 32.7% vs. 22.9%, chi(2) = 8.51, P = 0.004; smoking 8.8% vs. 4.4%, chi(2) = 6.17, P = 0.013); a higher percentage engaged in sexual intercourse (19.3% vs. 5.9%, chi(2) = 33.48, P = 0.000); ever seriously considered attempting suicide (23.7% vs. 15.4%, chi(2) = 8.09, P = 0.004), making a plan about how would attempt suicide (17.9% vs. 9.7%, chi(2) = 10.62, P = 0.001), being threatened or injured by someone with a weapon such as a knife, or club on school property (3.5% vs. 1.1%, chi(2) = 6.17, P = 0.013), being involved in physical fight (16.7% vs. 5.6%, chi(2) = 27.05, P = 0.000) during the 12 months preceding the survey.
CONCLUSIONSThe results further showed that the CSA of girls in our country is not uncommon, as reported before in our country and in the other countries and is associated with poor mental health and risky behaviors. The findings highlight the urgent need for the further research into CSA epidemiological characteristics, health services for the victims abused sexually, sexual abuse prevention programs in schools and the general community in China.
Adolescent ; Adult ; Child ; Child Abuse, Sexual ; psychology ; statistics & numerical data ; China ; Female ; Humans ; Mental Health ; Risk Factors ; Socioeconomic Factors ; Students, Medical ; psychology ; Surveys and Questionnaires
7.A systematic review: how to choose appropriate health-related quality of life (HRQOL) measures in routine general practice?
Tian-Hui CHEN ; Lu LI ; Michael M KOCHEN
Journal of Zhejiang University. Science. B 2005;6(9):936-940
In more recent times, health-related quality of life (HRQOL) measurements have formed an important part of assessing the quality of routine care in general practice. For a measure to have clinical usefulness it must not only be valid, appropriate, reliable, responsive, and capable of being interpreted, but it must also be simple, fast to complete, easy to score, and provide useful clinical data. The Two-step method of choosing appropriate measures is introduced. Then through comparison of generic instruments with disease-specific instruments, we can conclude that sometimes a combination of generic and disease-specific HRQOL measures may be more appropriate for monitoring changes in a patient's health status due to an intervention.
Family Practice
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Humans
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Outcome Assessment (Health Care)
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Quality Assurance, Health Care
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Quality of Life
8.Aneurysm Coil Embolization Using a 1.5-Fr Distal Outer Diameter Microcatheter.
David A STIDD ; Demetrius K LOPES ; Michael CHEN
Neurointervention 2014;9(1):39-44
The current assortment of microcatheters widely used for aneurysm coil embolization may not be well suited for several anatomic variants, including excessive vascular tortuosity and small aneurysms less than 3 mm. Longer microcatheters designed with a smaller caliber that can accommodate and deliver coils may be of use in these situations. This case series and literature review illustrates the advantages and limitations of the Marathon microcatheter (Covidien, Irvine, CA, USA) when used for coil embolization of cerebral aneurysms. Despite some technical compromises including the distal marker, length, and the risk of buckling, the Marathon microcatheter was able to adequately deliver coils to achieve satisfactory occlusion of cerebral aneurysms. We found unique advantages with regards to length and smaller distal outer diameter (OD). These results may serve as a guide for the further development of a microcatheter used for coil embolization that has the features of a smaller distal OD and longer length.
Aneurysm*
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Embolization, Therapeutic*
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Endovascular Procedures
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Intracranial Aneurysm
9.Prevalence of childhood sexual abuse among 2508 college students in 6 provinces of China
Jing-Qi CHEN ; Ping HAN ; Guang-Li LIAN ; Dunne P. MICHAEL
Chinese Journal of Epidemiology 2010;31(8):866-869
Objective To assess the prevalence of childhood sexual abuse (CSA) in college students and to explore the association of CSA with youth mental health problem. ethods A retrospective survey was conducted among 2508 students (females 1360, males 1148) in Nov. 2003to Mar. 2004. The students were from 6 colleges/universities in Beijing, Hebei, Shanxi, Jiangsu,Shaanxi and Anhui provinces of China. Results Of the 2508 students, 24.8% of females and 17.6%of males reported one or more types of nonphysical contact CSA (females 20.0% vs.males 14.6%) or/and physical contact CSA (females 14.1% vs. males 7.8% ) before the age of 16 years. Risk of any CSA was not associated with the existence of siblings (one-child vs. two-or more child families),rural/non-rural residence during childhood, or parental education. Compared with their peers who had no CSA, the students with CSA showed significantly higher mean scores of psychological symptoms of somatization, obsessiveness, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation and psychoticism. Conclusion The problem of CSA was not uncommonand there was a significant correlation between CSA experience and students mental health problems.More attention should be paid on CSA prevention and provision of health services for the victims.
10.Impact of genetic variation of tumor necrosis factor-alpha on gestational hypertension.
You-peng CHEN ; Thiemo PFAB ; Torsten SLOWINSKI ; Claus-Michael RICHTER ; Michael GODES ; Berthold HOCHER
Chinese Medical Journal 2006;119(9):719-724
BACKGROUNDThe mechanisms responsible for the pathogeneses of gestational hypertension and preeclampsia are unclear. Tumor necrosis factor-alpha (TNF-alpha) is a pro-inflammatory Th(1)-type cytokine. TNFA gene is located in the human leukocyte antigen (HLA) class III region of the major histocompatibility complex (MHC) on chromosome 6. The high TNF-alpha mRNA expression may be associated with the TNF2 (A) allele, which is the polymorphism of TNF-alpha at position -308 in promoter region. This study assessed whether the TNF2 (A) allele at position -308 plays a role in the alteration of blood pressure (BP) and urinary protein excretion during pregnancy.
METHODSThe original prospective cohort study comprised 1623 pregnant women from January 2000 to October 2001. The G/A polymorphism was done by restriction fragment length polymorphism (RFLP) analysis with Nco I enzyme.
RESULTSThe distributions of the G/A polymorphism of TNF-alpha in the promoter region at position -308 were wild-type 72.4% and variant 27.6%, respectively. The frequency of TNF2 (A) allele was approximately 0.15 for Caucasian pregnant women in the study. It was not significantly different in the distributions of genotypes and G/A allele frequencies among the three groups of pregnant women with gestational hypertension, preexisting hypertension and normal blood pressure (P > 0.05). The maternal blood pressure in the third trimester was significantly higher in the group of women possessing the TNF2 (A) allele compared to homozygous for the TNF1 (G) allele (systolic BP, P < 0.01 and diastolic BP, P < 0.05). The elevated blood pressure in the TNF2 (A) group was accompanied by higher urinary protein excretion in the third trimester (P < 0.05). The blood pressure and urinary protein excretion did not change apparently between the two groups in the first and second trimesters (P > 0.05).
CONCLUSIONSMaternal TNF2 (A) allele of TNF-alpha promoter region at position -308 could play a role in the alteration of blood pressures and/or enhancement of urinary protein excretion during pregnancy, and might play an important role in the development of both gestational hypertension and preeclampsia.
Adolescent ; Adult ; Cohort Studies ; Female ; Genetic Variation ; Humans ; Hypertension, Pregnancy-Induced ; genetics ; Middle Aged ; Polymorphism, Genetic ; Pregnancy ; Promoter Regions, Genetic ; Prospective Studies ; Proteinuria ; genetics ; Tumor Necrosis Factor-alpha ; genetics