Assessing Liver Function by T1 Maps on Gd-EOB-DTPA- Enhanced MRI for up to 50 Min in Rat Models of Liver Fibrosis: A Longer Hepatobiliary Time Period may Help

Objectives To investigate whether a longer time period of gadolinium ethoxybenzyl diethylenetriaminepen-taacetic add(Gd-EOB-DTPA)-enhanced T1 mapping scanning,as well as dynamic contrast-enhanced(DCE)and multiple hepatobiliary phase magnetic resonance imaging(MRI)have the potential to provide information about liver function in rats with liver fibrosis.Methods Forty rats were divided into the carbon tetrachloride-induced hepatic injury groups[carbon tetrachloride for four(n=14),eight(n=8),or twelve(n=8)weeks]and the control group(n=10).Gd-EOB-DTPA-enhanced MRI was performed including T1-mapping(delayed to 50 min),DCE,and multiple hepatobiliary phases.Indocyanine green retention rate at 15 min(ICG-R15)was determined.Parameters such as T1 reduction rate(△T1),elimination half-life of △T1(T_(△T1 1/2)),relative enhancement(RE),time to maximum RE(T_(max)),and perfusion parameters were calculated.Pearson correlation analysis was used for correlation analysis between ICG-R15 and each MRI indices.Results △T1 at 30,40,and 50 min showed significant positive correlations with ICG-R15(r=0.784,0.653,0.757,P=0.007,0.041,0.030).T_(△T1 1/2) showed a significant positive correlation with ICG-R15(r=0.685,P=0.029).showed a significant positive correlation with ICG-R15(r=0.532,P=0.019).Conclusions △T1 in the late hepatobiliary phase and T_(△T1 1/2) exhibited moderate correlations with liver function.The longer time period of Gd-EOB-DTPA-enhanced Tl mapping scanning,as well as DCE and multiple hepatobiliary phases,may be of some value for estimating liver function in rats with liver fibrosis.

Functional Variant of C-689T in the Peroxisome Proliferator-Activated Receptor-γ2 Promoter is Associated with Coronary Heart Disease in Chinese Nondiabetic Han People

Objective To investigate the association between the polymorphism of C-689T in the peroxisome proliferator-activated receptor-γ2 （PPARγ2） promoter and coronary heart disease （CHD）. Methods This case-controlled study was conducted in nondiabetic Chinese Han people, which enrolled 455 patients with CHD （cases） and 693 subjects without CHD （controls）. Data of clinical indexes were collected, including height, body weight, waist circumstance, systolic blood pressure （SBP）, diastolic blood pressure （DBP）, smoking, drinking, physical activity, as well as body mass index （BMI）. Fasting blood glucose （FBG）, plasma total cholesterol （TC） and triglyceride （TG） levels were measured. Polymerase chain reaction-restricted fragments length polymorphism （PCR-RFLP） was used to determine the PPARγ2 promoter C-689→T substitution. The genotype distribution of PPARγ2 promoter C-689T, allelic frequency, clinical indexes, and laboratorial measurements were compared between the two groups. The effect of genotype on the risk of CHD was assessed using univariate and multivariate regression model. Results The genotype frequencies of CC, CT and TT in PPARγ2 promoter C-689T were 89.7%, 9.9% and 0.4% in the case group, and 93.1%, 6.6% and 0.3% in the control group, respectively （CC vs. CT＋TT, χ^2= 6.243, P=0.041）. Carriers of -689T allele （n=95） had significantly higher TC level than non-carriers （n=1053） （5.12±1.26 vs. 4.76±1.22 mmol/L, P=0.001）. Male carriers of -689T allele （n=51） were significantly higher in waist circumference, body weight, TC and TG than male non-carriers （n=656） （all P〈0.05）. In subjects whose BMI was over 25 kg/m2, carriers of -689T allele （n=82） had significantly higher levels of waist circumference, BMI, SBP and TC than non-carriers （n=231） （all p〈0.05）. The -689T allele was an independent risk factor for CHD （OR=1.668, 95%CI： 1.031-2.705, P=0.037） after adjusting for age, gender, waist circumference, body weight, BMI, smoking, physical activities, SBP, DBP, FBG, TC and TG level. Conclusion These data support the hypothesis that the -689T allele is associated with an increased risk of CHD, in Chinese Han people and correlates significantly with the profiles of CHD-related risk factors.

Immunosuppressive Treatment of Non-infectious Uveitis:History and Current Choices

Non-infectious uveitis is one of the leading causes of preventable blindness worldwide. Long-term immunosuppressive treatment is generally required to achieve durable control of inflammation in posterior and panuveitis. Although systemic corticosteroids have been the gold standard of immunosuppressive treatment for uveitis since first introduced in 1950 s,its side effects of long-term use often warrant an adjuvant treatment to reduce the dosage/duration of corticosteroids needed to maintain disease control. Conventional immunosuppressive drugs,classified into alkylating agent,antimetabolites and T cell inhibitors,have been widely used as corticosteroid-sparing agents,each with characteristic safety/tolerance profiles on different uveitis entities. Recently,biologic agents,which target specific molecules in immunopathogenesis of uveitis,have gained great interest as alternative treatments for refractory uveitis based on their favorable safety and effectiveness in a variety of uveitis entities. However,lack of large randomized controlled clinical trials,concerns about efficacy and safety of long-term usage,and economic burden are limiting the use of biologics in non-infectious uveitis. Local administration of immunosuppressive drugs(from corticosteroids to biologics) through intraocular drug delivery systems represent another direction for drug development and is now under intense investigation,but more evidences are needed to support their use as regular alternative treatments for uveitis. With the numerous choices belonging to different treatment modalities(conventional immunosuppressive agents,biologics and local drug delivery systems) on hand,the practice patterns have been reported to vary greatly from center to center. Factors influence uveitis specialists' choices of immunosuppressive agents may be complex and may include personal familiarity,treatment availability,safety/tolerability,effectiveness,patient compliance,cost concerns and suggestions from related specialists such as rheumatologists and pediatricians. The focus of this review is to provide an overview of each treatment modality on safety/tolerability and effectiveness,which are believed to be the two most important factors affecting treatment decision making.

Plasma SCF/c-kit Levels in Patients with Dipper and Non-Dipper Hypertension

Objective The aim of this study was to investigate the relationship between peripheral plasma stem cell factor (SCF)/c-kit levels and the types of dipper and non-dipper hypertension in hypertensive patients.Methods This cross-sectional study included newly diagnosed hypertensive patients who underwent 24-hour ambulatory blood pressure monitor (ABPM) between January 2009 and 2012 in Jiangning city. Patients were divided into the dipper group and the non-dipper group according to ABPM measurements. The levels of SCF and its receptor c-kit, tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) in peripheral blood were measured via enzyme-linked immunosorbent assays. The serum levels of glucose and lipid were examined as well. The levels of SCF/c-kit were compared between the dippers and the non-dippers; and their correlation with 24-hour mean systolic blood pressure (MSBP), 24-hour mean diastolic blood pressure (MDBP), TNF-αand IL-6 were investigated using linear regression analyses statistically.Results A total of 247 patients with newly diagnosed hypertension were recruited into the study, including 116 non-dippers and 131 dippers. The levels of peripheral plasma SCF were higher in non-dipper group (907.1±52.7 ng/L vs. 778.7±44.6 ng/L; t=2.837, P<0.01), and the levels of c-kit were higher in non-dipper group too (13.2±1.7 μg/L vs 9.57±1.4 μg/L; t=2.831, P<0.01). Linear regression analysis revealed that SCF/ckit levels were significantly positively correlated with MSBP, MDBP, plasma TNF-α, and IL-6 levels (all P<0.01).Conclusions Peripheral plasma SCF/c-kit levels are higher in patients with non-dipper hypertension than those with dipper one, and significantly correlate with 24-hour MSBP, 24-hour MDBP, serum TNF-α and IL-6 levels.

Introduction of Obstructive Sleep Apnea in Adults

Obstructive sleep apnea(OSA) in adults is a common disease,usually associated with cardiovascular disease and metabolic syndrome.Though involving many medical disciplines,it is often overlooked by physicians.In the past two decades,the population of obese people has greatly increased.As obesity is a major risk factor of OSA,it

Observation of Insulin Exocytosis by a Pancreatic β Cell Line with Total Internal Reflection Fluorescence Microscopy

INSULIN secretion was traditionally measured with biochemical and immunological methods such as enzyme linked immunosorbant assay and radioimmunoassay. However, these methods can only tell the amount of insulin secreted; they give no information about the secretion process or mechanism of exocytosis. In recent years, an imaging technique known as total internal reflection fluorescence （TIRF） microscopy has been employed to study insulin secretion.

Pharmacokinetic Study of a Novel Recombinant Human Granulocyte Colony-stimulating Factor in Rats

Objective To study the pharmacokinetics of a novel recombinant human granulocyte colonystimulating factor (rhG-CSFa) in rats and to determine the proteolytic rates of rhG-CSFa in the whole blood and serum of rats in vitro. Methods The pharmacokinetics of rhG-CSFa and conventional (wild type,WT) granulocyte colonystimulating factor (G-CSF) were investigated in Sprague-Dawley rats which received either intravenous or subcutaneous injection of rhG-CSFa or WT G-CSF at three different doses (20,50,or 100 μg/kg). The blood samples of rats were collected at multiple time points (from 0.08 to 12 h) and the concentrations of rhG-CSFa and WT G-CSF in serum were determined with a sandwich enzyme-linked immunosorbent assay (ELISA). For the study of proteolytic rates in vitro,the concentrations of rhG-CSFa or WT G-CSF were determined at 3-minute intervals after addition of the respective drug to rat’s whole blood or serum. Results Pharmacokinetic analysis of serum rhG-CSFa or WT G-CSF levels indicated that,at each dose tested,for either route of drug administration,the area under concentration-time curve values and the maximum serum concentration of rhG-CSFa were higher than those of WT G-CSF,and the serum half life of rhG-CSFa was longer than that of WT G-CSF. Subsequent in vitro whole blood and serum stability study showed that the rates of drug degradation in WT G-CSF were 1.8 folds and 1.5 folds higher than those in rhG-CSFa,respectively. Conclusion rhG-CSFa has better serum and whole blood stability in vitro and higher bioavailability in vivo as compared to WT G-CSF.

High Serum Resistin Level may be an Indicator of the Severity of Coronary Disease in Acute Coronary Syndrome

Objective To investigate the correlation between serum resistin level, cardiovascular risk factors and severity of coronary disease in acute coronary syndrome （ACS）. Methods Alter evaluated by clinical history, electrocardiography, exercise tolerance tests, laboratory tests, and coronary angiography, 220 consecutive patients with suspected chest pain were divided into normal control group, stable angina pectoris （SAP） group, and ACS group, respectively. Baseline clinical characteristics, including height, weight, waist circumference, hip circumference, white blood cell count, high-sensitive C-reactive protein （hsCRP）, total cholesterol, triglyceride, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, were compared among three groups. ELISA was used to detect serum resistin levels. Pearson＇s correlation coefficient analysis was used to assess association between resistin and other traditional cardiovascular risk factors. Multinomial logistic regression analyses were used to define the relationship between serum resistin level and SAP or ACS. Results Serum resistin level in ACS group （1.18±0.48 μg/L） was significantly higher than that in normal control and SAP groups （0.49±0.40 and 0.66±0.40 μg/L; P〈0.01）. Only in ACS group, increased serum resistin level was significantly correlated with hsCRP （r=0.262, P=0.004） and white blood cell count （r=0.347, P=0.001）. Furthermore, serum resistin levels showed a stepwise increase with the number increase of 〉 50% stenosed coronary vessels. Multinomial logistic regression test demonstrated that serum resistin was a strong risk factor for ACS （OR=29.132, 95 % CI： 10.939-77.581, P〈0.001）. Conclusion These findings suggested the potential role of resistin in atherosclerosis and especially its involvement in ACS.

Effects of Glutamine Supplementation on Patients Undergoing Abdominal Surgery

Objective To evaluate the effects of supplementation of glutamine （GLN） on maintaining glu- tathione （GSH） level, immune system function, liver function, and clinical outcome of patients receiving abdominal operation. Methods Forty patients undergoing elective abdominal surgical treatment were randomly divided into 2 groups： study group （n=20） and control group （n=20）. All patients received total parenteral nutrition （TPN） for up to 7 days during perioperative period. The study group received TPN supplemented with GLN dipeptide while the control group received TPN without GLN dipeptide. Patients in both groups received equivalent nitrogen and caloric intake. Blood sample was taken on preoperative day, and the 1st, 3rd, 6th postoperative day to measure GSH level, immune indexes, and liver function indexes. Results The decrease of GSH level in plasma and red blood cell （RBC） in study group was less than that in control group during postoperative period. Ratio of GSH/glutathione disulfide （GSSG） in plasma in study grouP was higher than that in control group on the 3rd postoperative day （52.53±11.46 vs. 31.43±7.27, P = 0.001）. Albumin level in study group was higher than that in control group on the 3rd postoperative day （37.7±3.8 g/L vs. 33.8±4.2 g/L, P = 0.02）. There was no significant difference in the levels of immunoglobin （IgG, IgM, IgA） or T lymphocyte subgroup （CD4, CD8, CD4/CD8） in both groups during postoperative period. There was one case with infectious complication in control group, while none in study group. A trend of shortened hospital stay was observed in study group compared with control group （22.3±2.1 d vs. 24.9±1.7 d,P= 0.32）. Conclusions Supplementation of GLN-enriched TPN has beneficial effects on maintaining GSH levels in plasma and RBC, sustaining GSH/GSSG ratio and albumin level, and keeping antioxidant abilities during postoperative period in patients with abdominal operation, with the trends of decreasing incidence of infectious complication and shortening hospital stay.

EFFECTS OF EARLY NUTRITION INTERVENTION ON IGF1, IGFBP3,INTESTINAL DEVELOPMENT, AND CATCH-UP GROWTH OF INTRAUTERINE GROWTH RETARDATION RATS

To investigate the effects of early nutritional intervention on the serum insulin-like growth factor-1 (IGF1),insulin-like growth factor binding protein 3 (IGFBP3), intestinal development, and catch-up growth of intrauterine growth retardation (IUGR) rats by giving the IUGR new born rats different protein level diet. Methods IUGR rat model was built by starvation of pregnant female rats. Twenty-four IUGR pups and 8 normal pups were divided randomly into 4 groups: normal control group (C group); IUGR control group(S group), IUGR low-protein diet group (SL group), and IUGR high-protein diet group (SH group). Detected the serum IGF1, IGFBP3, body weight, body length, intestinal weight length, intestinal villi height (VH), crypt depth (CD), villi absorbing area (VSA), mucous thickness (MT), and disaccharidase at the 4th week. Results (1) The SH group showed the fastest catch-up growth, serum IGF1, IGFBP3, VH, and VSA were significantly higher than those of normal control group and IUGR control group. The intestinal weight and length, and the activities of lactase and saccharase of the SH group also reached the normal control group level. (2) The SL group kept on small size, the serum IGF1, IGFBP3, and most of intestinal histological indexes were all significantly lower than other groups. (3) IGF-1, IGFBP3 were positively correlated to intestinal VH, VSA, saccharase, body weight and length. Conclusions The serum IGF1 was a sensitive index to the catch-up growth. The early nutritional intervention of high-protein diet after birth is helpful for the catch-up growth of IUGR through promoting the intestinal development and the ab-sorption of nutrition

CLINICAL APPLICATION OF THE TRAFIXINSTRUMENTATION IN CORRECTING SCOLIOSIS

To evaluate the results of the TRAFIX instrumentation in correcting s coliosis. Methods. Since October 1997, 47 patients with scoliosis received spinal fixation with the TRAFIX instrumentation at the Peking Union Medical College Hospital. T he average age was 14.3 years (range 10 to 38 years). There were 27 idiopathic c ases, 16 congenital cases, 2 cases with Marfan syndrome and 2 with neurofibromat osis. Twelve of the 47 patients underwent anterior release, while 4 patients rec eived the revision approach. The average follow up time was 26 months (13～38 m onths). Results. The measurements of primary coronal deformity before and after surgery were 74°(50°～115°) and 38.7° (11°～95°), respectively. The average curve correction was 54%. The average number of fused segments was 12.5 (7～17) verte brae. The distance between the center of apex and the C7 plumb line was 56.8 mm before surgery (25～107mm) and 31 mm after surgery (10～87mm). Conclusion. The TRAFIX instrumentation provides three dimensional correction wi th refinement, convenience and reliable fixation.

COMPARATIVE STUDY OF FIBRONECTIN GENE EXPRESSION IN TISSUES FROM HYPERTROPHIC SCARS AND DIABETIC FOOT ULCERS

Objective.To explore the expression characteristic of fibronectin gene in hypertr ophic scars and diabetic ul-cer tissues.Methods.The biopsies from normal skins,hypertrophic scars and diabetic foot ulc ers were taken.The tech-nique of quantitative polymerase ch ain reaction(PCR)was used to evaluate the gene express ion of fibronectin in the above biopsies.Results.Fibronectin gene expression was enhanced in hypertrophic scars and decreased in diabetic foot ul-cers compared with that in normal ski ns.Quantitative comparison showed about 2-fold increase of fibronectin mR-NA level in hypertrophic scars and ab out 3-fold decrease of fibronectin mRNA level in diabetic ulcers as com-pared with that in normal skins.Conclusions.Fibronectin gene expression is influenced by the tissue environment.Di fferent expression and synthesis of fibronectin may cause d ifferent outcomes in wound healing.

SURGICAL TREATMENT OF MALIGNANT ESOPHAGEAL TUMORS IN PUMC HOSPITAL

To study how to prolong the postoperative survival time of the patients with malignant esophageal tumors. The clinical data of 1098 patients with malignant esophageal tumors from 1961 to 1992 were retrospectively analyzed. The deletion of fragile histamine triplet (FHIT) gene (a tumor suppressor gene) in 30 fresh esophageal samples obtained in 1996 was detected with PCR and RT PCR method. The resectability was raised gradually and the operative morbidity and mortality decreased year by year, but there was no significant improvement on the postoperative 5 year survival rate. Delayed diagnosis and irradical resection influenced the long term survival. The deletion of cDNA of FHIT gene was 64.2% in esophageal cancer and 20% in the resected margin of the cancer. We believe that high grade atypical hyperplasia in esophageal epithelium and deletion of FHIT gene in esophageal cancer and its resected margin are pathological and molecular markers for early diagnosis of esophageal cancer respectively, and the latter may be one of the molecular markers for the resection. Early diagnosis and treatment, radical resection, and postoperative nutritional support are very important for the improvement of the postoperative survival time of the patients.

CARTILAGE- LIKE PHENOMENON IN THE ANTERIOR CRUCIATE LIGAMENT

Objective. To detect histological characteristic of anterior cruciate ligament (ACL) and medial collateral ligament (MCL). Methods. In each of 20 skeletally mature male mongrels and 4 men, the ACL and MCL were examined by standard hematoxylin- eosin procedure and toluidine blue staining for histologic observation. Results. The fibroblasts in medial collateral are elongated to spindle shape and aligned in a row between the bundles of collagenous fibers. Toluidine blue staining is negative. The anterior cruciate ligament demonstrated more heterogenous cell types and arrangement. It had three major cell forms:spindle, round and ovoid type, which were shorter but greater than the cells in medial collateral ligament. Toluidine blue staining was positive in anterior cruciate ligament. Most cells in anterior cruciate ligament were enclosed within lacunae. Conclusion. This study suggests that the ACL has different histological characteristics from MCL, and is more cartilage- like in nature.

FEASIBILITY STUDY OF AN ULTRASOUND CONTRAST AGENT(LEVOVIST) IN COLOR DOPPLER IMAGING OF LIVER NEOPLASMS

The purpose of this study was to determine the efficacy of using an ultrasound contrast agent(levovist)to enhance the color Doppler imaging of liver neoplasms.Thirty patients with hepatic tumors were enrolled in this study.After intravenous administration of levovist,the color Doppler signals of normal hepatic vessels were enhanced.In various hepatic tumors,the different patterns of tumor vascularity were observed,which had not been demonstrated in conventional non contrast color Doppler imaging.In 11 of 16 patients with hepatocarcinoma,additional color Doppler signals were observed in the central part of the tumors.On the contrary,3 patients with metastatic liver lesions the enhanced color Doppler signals appear only at the peripheral of tumors.A typical rim like color enhancement was seen in 2 of the 3 cases.In six patients with hepatic hemangiomas contrast enhanced color Doppler imaging demonstrated the blood vessels at the margin of the neoplasms.Contrast enhanced color Doppler imaging improves the visualization of the hepatic neoplasm vascularity.This technique holds great promise for detecting small liver tumors and differentiating hepatic neoplasms.

OVEREXPRESSION OF p53, EGFR,C-ERBB2 AND C-ERBB3 IN ENDOMETRIOIDCARCINOMA OF THE OVARY

Objectives. To determine overexpression of p53, EGFR, c-erbB-2 and c-erbB-3 in endometrioid carcinoma of the ovary and to evaluate the prognostic significance of these results, especially, coexisting overexpression of p53 and one of the member of type I growth factor receptor family.Methods. Overexpressions of the p53, EGFR, c-erbB-2 and c-erbB-3 protein were studied by im-munohistochemistry in paraffin-embedded tumor tissue from 28 patients with endometrioid carcinoma of the ovary.Results. 11 (39.3%), 13 (46. 4%), and 14 (50. 0%) were stained positively with p53, c-erbB-2 and c-erbB-3 monoclonal antibodies. 13 (46- 4%) was stained positively with EGFR polyclonal antibody. There were no relationship between p53, EGFR, C-erbB-2, c-erbB-3 and histologic grade, lymph node metastasis. The percentage of tumors with over expression of p53, EGFR, C-erbB-2 and c-erbB-3 was higher in those with stage Ⅱ-Ⅲ tumors compared with those with stage Ⅰ , in patients with residual tumor after initial surgery compared with those without. A high survival rate was observed in patients without p53, EGFR, c-erbB-2 and c-erbB-3 overexpression respectively than those with. A highest survival rate was observed in patients with both p53 and one of EGFR, c-erbB-2 and c-erbB-3 negative compared with those both positive or either of both positive.Conclusion. Overexpression of p53, EGFR, c-erbB-2 and C-erbB-3 resulted in a poorer prognosis respectively. Overexpression of both p53 and one of the EGFR, c-erbB-2 and c-erbB-3 is a worse prognostic indicator in patients with endometrioid carcinoma of the ovary.

APPLICATION OF POLYMERASE CHAIN REACTION FOR DIAGNOSING AMEBIC LIVER ABSCESS

Polymerase chain reaction (PCR) has been applied in diagnosing amebic liver infection by detecting pathogenic Entamoeba histolytica DNA in liver aspirates. Oligonucleotide primers found to be specific for the gene encoding the 30 kDa molecule of this pathogenic ameba were used in the test. Liver aspirates obtained from 23 patients with amebic liver abscess substantiated by typical clinical manifastation or with very high titres of anti-E histolytica antibedies by ELISA were found to be positive by PCR. Fourteen control samples (3 cases of bacterial liver abscess, I of liver cancer and 10 of other abscess) were all found to be negative to this reaction- The results suggested PCR to be a specific and sensitive tool for diagnosing amebic liver abscess infections.