Humans ; Severe Acute Respiratory Syndrome ; pathology ; Specimen Handling

Adolescent ; Adult ; Aged ; Blood Glucose ; analysis ; Cross-Over Studies ; Diabetes Mellitus ; blood ; drug therapy ; Female ; Glycated Hemoglobin A ; analysis ; Humans ; Insulin ; analogs & derivatives ; therapeutic use ; Insulin Lispro ; Male ; Middle Aged

OBJECTIVETo study the characteristics of host immune response against human gastric carcinoma of different histological types.

METHODSThe expression of 24 families of T cell receptor beta chain variable region (TCRVbeta) and cytokine profiles in isolated CD4(+) and CD8(+) subsets, as well as the cytokine profiles in purified epithelial cells from the tumor tissue and the residual benign tissue of patients with gastric carcinoma, was detected by a highly sensitive radioactivity labeled semi-quantitative RT-PCR technique.

RESULTSThe number of expanded T cell clones in CD8(+) subset from tumor tissue of the intestinal-type carcinoma was larger than that of diffuse-type (P = 0.046). The mRNA levels of IL-6, IL-8 in CD8(+) T subset, as well as the level of TNF-alpha in CD4(+) T subset from the tumor tissue of the diffuse type (0.61 +/- 0.29, 0.56 +/- 0.22, 0.09 +/- 0.03) were significantly higher than that from the residual benign tissue (0.14 +/- 0.05, 0.27 +/- 0.09, 0.04 +/- 0.02; P = 0.028, P = 0.043, P = 0.046). However, the mRNA level of IL-8 in CD8(+) subset and epithelial tumor cells of the intestinal-type (0.57 +/- 0.25, 0.27 +/- 0.07) was significantly higher than that from the residual benign tissue (0.21 +/- 0.07, 0.14 +/- 0.06; P = 0.028, P = 0.028).

CONCLUSIONSThe characteristics of host immune response against tumor are different between intestinal-type and diffuse-type gastric carcinoma. Both fewer expanded T cell clones and more suppressive cytokines suggest a more suppressive immune status in the local tumor lesion of diffuse-type than in the intestinal-type of the gastric carcinoma.

Adult ; Aged ; Aged, 80 and over ; CD4-Positive T-Lymphocytes ; metabolism ; pathology ; CD8-Positive T-Lymphocytes ; metabolism ; pathology ; Clone Cells ; Cytokines ; genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Interferon-gamma ; genetics ; Interleukin-10 ; genetics ; Interleukin-2 ; genetics ; Interleukin-4 ; genetics ; Interleukin-6 ; genetics ; Interleukin-8 ; genetics ; Interleukins ; Male ; Middle Aged ; RNA, Messenger ; genetics ; metabolism ; Receptors, Antigen, T-Cell, alpha-beta ; genetics ; Stomach Neoplasms ; genetics ; immunology ; pathology ; T-Lymphocytes ; metabolism ; pathology ; Transforming Growth Factor beta ; genetics ; Tumor Necrosis Factor-alpha ; genetics

BACKGROUNDThere are studies suggesting smoking may increase the risk of type 2 diabetes. Effects of smoking on insulin secretion and insulin resistance (IR) are, however, controversial.

METHODSThis is a cross-sectional study. Since there were very few smokers among Hong Kong Chinese women, only men (n = 1068) were analyzed in this report. Fasting and 2-hour plasma glucose and insulin were measured. Insulinogenic index as well as beta-cell function and IR based on homeostatic model assessment (HOMA) by computer model (HOMA Calculator v2.2) were calculated.

RESULTSOf the 1068 men, 147 had newly diagnosed diabetes, 131 newly diagnosed impaired glucose tolerance (IGT) and 790 were non-diabetic normal controls. Smokers had similar fasting and 2-hour insulin levels, insulinogenic index and HOMA derived beta-cell function as compared to non-smokers in the groups with diabetes, IGT or normal oral glucose tolerance test (OGTT). IR was also similar between smokers, ex-smokers and non-smokers in those with normal OGTT. In men with IGT or diabetes, after adjustment for age and body mass index, smokers were more insulin resistant as compared to non-smokers (IR, IGT: 1.59 +/- 1.07 vs 1.03 +/- 0.54, P < 0.05; diabetes: 1.96 +/- 1.36 vs 1.06 +/- 0.45, P < 0.01). With Logistic regression analysis, comparing smokers and non-smokers, IR was independently associated with smoking (odds ratio (95% CI), IGT: 2.23 (1.05, 4.71); diabetes: 3.92 (1.22, 12.58)). None of the other insulin parameters enter into the model among those with normal OGTT or comparing ex-smokers and non-smoker or smokers and ex-smokers.

CONCLUSIONSIn Chinese men, smoking did not show any direct association with insulin levels and pancreatic insulin secretion. Smoking men with IGT or diabetes appeared more insulin resistant than their non-smoking counterparts.

Adult ; Female ; Glucose Intolerance ; metabolism ; Humans ; Insulin ; secretion ; Insulin Resistance ; Insulin-Secreting Cells ; secretion ; Male ; Middle Aged ; Smoking ; metabolism

BACKGROUNDVon Hippel-Lindau (VHL) syndrome is an autosomal dominant familial cancer syndrome predisposing the affected individuals to multiple tumours in various organs. The genetic basis of VHL in Southern Chinese is largely unknown. In this study, we characterized the mutation spectrum of VHL in nine unrelated Southern Chinese families.

METHODSNine probands with clinical features of VHL, two symptomatic and eight asymptomatic family members were included in this study. Prenatal diagnosis was performed twice for one proband. Two probands had only isolated bilateral phaeochromocytoma. The VHL gene was screened for mutations by polymerase chain reaction, direct sequencing and multiplex ligation-dependent probe amplification (MLPA).

RESULTSThe nine probands and the two symptomatic family members carried heterozygous germline mutations. Eight different VHL mutations were identified in the nine probands. One splicing mutation, NM_000551.2: c.463+1G > T, was novel. The other seven VHL mutations, c.233A > G [p.Asn78Ser], c.239G > T [p.Ser80Ile], c.319C > G [p.Arg107Gly], c.481C > T [p.Arg161X], c.482G > A [p.Arg161Gln], c.499C > T [p.Arg167Trp] and an exon 2 deletion, had been previously reported. Three asymptomatic family members were positive for the mutation and the other five tested negative. In prenatal diagnosis, the fetuses were positive for the mutation.

CONCLUSIONSGenetic analysis could accurately confirm VHL syndrome in patients with isolated tumours such as sporadic phaeochromocytoma or epididymal papillary cystadenoma. Mutation detection in asymptomatic family members allows regular tumour surveillance and early intervention to improve their prognosis. DNA-based diagnosis can have an important impact on clinical management for VHL families.

Asian Continental Ancestry Group ; DNA Mutational Analysis ; Humans ; Polymerase Chain Reaction ; Sequence Analysis, DNA ; Von Hippel-Lindau Tumor Suppressor Protein ; genetics ; von Hippel-Lindau Disease ; genetics

BACKGROUND: To determine the frequency of chronic kidney disease (CKD) and its associated risk factors in Chinese type 2 diabetic patients, we conducted a cross-sectional study in Nanjing, China, in the period between January 2008 and December 2009. METHODS: Patients with type 2 diabetes under the care by Jiangsu Province Official Hospital, Nanjing, China were invited for assessment. CKD was defined as the presence of albuminuria or estimated glomerular filtration rate <60 mL/min/1.73 m2. Albuminuria was defined as urinary albumin-to-creatinine ratio > or =30 mg/g. RESULTS: We recruited 1,521 urban Chinese patients with type 2 diabetes (mean age, 63.9+/-12.0 years). The frequency of CKD and albuminuria was 31.0% and 28.9%, respectively. After adjusted by age and sex, hypertension, anemia and duration of diabetes were significantly associated with CKD with odds ratio (95% confidence interval) being 1.93 (1.28 to 2.93), 1.70 (1.09 to 2.64), and 1.03 (1.00 to 1.06), respectively. CONCLUSION: In conclusion, CKD was common in the urban Nanjing Chinese with type 2 diabetes. Strategies to prevent or delay progression of kidney disease in diabetes should be carried out at the early disease course of type 2 diabetes.
Albuminuria ; Anemia ; Asian Continental Ancestry Group ; China ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2 ; Glomerular Filtration Rate ; Humans ; Hypertension ; Kidney Diseases ; Odds Ratio ; Renal Insufficiency, Chronic ; Risk Factors

BACKGROUND/AIMS: The application of glycated hemoglobin (HbA1c) for the diagnosis of diabetes is currently under extensive discussion. In this study, we explored the validity of using HbA1c as a screening and diagnostic test in Chinese subjects recruited in Nanjing, China. METHODS: In total, 497 subjects (361 men and 136 women) with fasting plasma glucose (PG) > or = 5.6 mmol/L were recruited to undergo the oral glucose tolerance test (OGTT) and HbA1c test. Plasma lipid, uric acid, and blood pressure were also measured. RESULTS: Using a receiver operating characteristic curve, the optimal cutoff point of HbA1c related to diabetes diagnosed by the OGTT was 6.3%, with a sensitivity and specificity of 79.6% and 82.2%, respectively, and the area under the curve was 0.87 (95% confidence interval, 0.83 to 0.92). A HbA1c level of 6.5% had a sensitivity and specificity of 62.7% and 93.5%, respectively. When comparing the HbA1c > or = 6.5% or OGTT methods for diagnosing diabetes, the former group had significantly higher HbA1c levels and lower levels of fasting and 2-hour PG than the latter group. No significant difference was observed in the other metabolism indexes between the two groups. CONCLUSIONS: Our results suggest that HbA1c > or = 6.5% has reasonably good specificity for diagnosing diabetes in Chinese subjects, which is in concordance with the American Diabetes Association recommendations.
Aged ; Analysis of Variance ; *Asian Continental Ancestry Group ; Biological Markers/blood ; Blood Glucose/analysis ; China/epidemiology ; *Chromatography, High Pressure Liquid/standards ; *Chromatography, Ion Exchange/standards ; Diabetes Mellitus, Type 2/blood/*diagnosis/ethnology ; Fasting/blood ; Female ; Glucose Tolerance Test/standards ; Hemoglobin A, Glycosylated/*analysis ; Humans ; Male ; Mass Screening/*methods/standards ; Middle Aged ; Predictive Value of Tests ; ROC Curve ; Reference Standards ; Reproducibility of Results ; Sensitivity and Specificity

Background/Aims: Serum fibrosis scores comprised of common laboratory tests have high utility to assess severity of liver fibrosis. We aimed to derive and validate a hepatocellular carcinoma (HCC) risk score based on serum fibrosis scores to predict HCC in treatment-naïve chronic hepatitis B (CHB) patients. Methods: Fifteen thousand one hundred eighty-seven treatment-naïve adult CHB patients were identified to form the training cohort in this retrospective study. Individual fibrosis score was included to construct a new HCC prediction score. The score was externally validated in an independent treatment-naïve Korean CHB cohort. Results: 180/15,187 patients (1.2%) in training cohort and 47/4,286 patients (1.1%) in validation cohort developed HCC during a mean follow-up of 52 and 50 months, respectively. The newly developed HCC risk score, Liang score, is composed of gender, age, hepatitis B virus DNA, fibrosis-4 (FIB-4) index, and ranges from 0 to 22. Area under the time-dependent receiver operating characteristic curve of Liang score was 0.79 (95% confidence interval, 0.70–0.89). A cutoff value of nine provided an extremely high negative predictive value of 99.9% and high sensitivity of 90.0% at 5 years in the validation cohort. Patients with Liang score ≤9 had HCC incidence <0.2% per year in both training and validation cohorts, in whom HCC surveillance might be exempted. Conclusion A novel HCC risk score, Liang score, based on FIB-4 index, is applicable and accurate to identify treatment-naïve CHB patients with very low risk of HCC to be exempted from HCC surveillance.

Background/Aims: Serum fibrosis scores comprised of common laboratory tests have high utility to assess severity of liver fibrosis. We aimed to derive and validate a hepatocellular carcinoma (HCC) risk score based on serum fibrosis scores to predict HCC in treatment-naïve chronic hepatitis B (CHB) patients. Methods: Fifteen thousand one hundred eighty-seven treatment-naïve adult CHB patients were identified to form the training cohort in this retrospective study. Individual fibrosis score was included to construct a new HCC prediction score. The score was externally validated in an independent treatment-naïve Korean CHB cohort. Results: 180/15,187 patients (1.2%) in training cohort and 47/4,286 patients (1.1%) in validation cohort developed HCC during a mean follow-up of 52 and 50 months, respectively. The newly developed HCC risk score, Liang score, is composed of gender, age, hepatitis B virus DNA, fibrosis-4 (FIB-4) index, and ranges from 0 to 22. Area under the time-dependent receiver operating characteristic curve of Liang score was 0.79 (95% confidence interval, 0.70–0.89). A cutoff value of nine provided an extremely high negative predictive value of 99.9% and high sensitivity of 90.0% at 5 years in the validation cohort. Patients with Liang score ≤9 had HCC incidence <0.2% per year in both training and validation cohorts, in whom HCC surveillance might be exempted. Conclusion A novel HCC risk score, Liang score, based on FIB-4 index, is applicable and accurate to identify treatment-naïve CHB patients with very low risk of HCC to be exempted from HCC surveillance.

Background/Aims: We aimed to determine the association between blood urea level and incident cirrhosis, hepatic decompensation, and hepatocellular carcinoma in chronic liver disease (CLD) patients. Methods: The association between blood urea level and liver fibrosis/liver-related events were evaluated on continuous scale with restricted cubic spline curves based on generalized additive model or Cox proportional hazards models. Then, the above associations were evaluated by urea level within intervals. Results: Among 4,282 patients who had undergone liver stiffness measurement (LSM) by transient elastography, baseline urea level had a U-shaped association with LSM and hepatic decompensation development after a median follow-up of 5.5 years. Compared to patients with urea of 3.6–9.9 mmol/L, those with urea ≤3.5 mmol/L (adjusted hazard ratio [aHR], 4.15; 95% confidence interval [CI], 1.68–10.24) and ≥10 mmol/L (aHR, 5.22; 95% CI, 1.86–14.67) had higher risk of hepatic decompensation. Patients with urea ≤3.5 mmol/L also had higher risk of incident cirrhosis (aHR, 3.24; 95% CI, 1.50–6.98). The association between low urea level and incident cirrhosis and hepatic decompensation was consistently observed in subgroups by age, gender, albumin level, and comorbidities. The U-shaped relationship between urea level and LSM was validated in another population screening study (n=917). Likewise, urea ≤3.5 mmol/L was associated with a higher risk of incident cirrhosis in a territory-wide cohort of 12,476 patients with nonalcoholic fatty liver disease at a median follow-up of 9.9 years (aHR, 1.27; 95% CI, 1.03–1.57). Conclusions We identified a U-shaped relationship between the urea level and liver fibrosis/incident cirrhosis/hepatic decompensation in patients with CLD.