Volume 89  ·   Issue 10  ·  2009

Blood glucose monitoring is the basis of optimal management of diabetic patients. Based on the clinical monitoring results, it is helpful to judge the degree of glucose metabolism disorder, formulate hypoglycemic treatment plan, evaluate the treatment effect and guide the adjustment of treatment plan.

Objective To investigate the characteristics of glycemic excursion of different subtypes of glucose tolerance. Methods Assessed by oral glucose tolerance test (OGTT) repeated twice, 81 individuals were divided into 4 groups: normal glucose tolerance (NGT, n=18), isolated impaired fasting glycemia (IFG, n=12), isolated impaired glucose tolerance (IGT, n=19), combined IFG/IGT (n=11), and newly diagnosed type 2 diabetes mellitus (T2DM, n=21). And then continuous glucose monitoring system (CGMS) was used for 72 hours to monitor the blood glucose (BG) level before drug intervention. Results (1) The levels of largest amplitude of glycemic excursions (LAGE), mean blood glucose (MBG), and standard deviation of mean level of blood glucose fluctuation (SDBG) increased gradually with the deterioration of glucose tolerance. The mean amplitude of glucose excursion (MAGE) readout of the IGT group was (3.2±1.2) mmol/L , significantly higher than that of the NGT group [(1.6±0.5) mmol/L, P<0.05], and significantly lower than that of the T2DM group [(5.2±1.9) mmol/L, P<0.05]. The level of frequency of glucose excursion (FGE) decreased along with the decrease of glucose tolerance: NGT group [(6.1±3.4)] > IGT/IFG group [(5.5±2.5)] > T2DM group [(4. 8±1.8)]. Among the three components of IGR, the IGT group showed highest MAGE (3.2±1.2) mmol/L and lowest FGE level (4.9±1.8). (2) The level of absolute mean of daily difference (MODD) increased in the following order: NGT group [(0.8±0.3) mmol/L], IGT group [(1.1±0.4) mmol/L], IFG/IGT group [(1.2±0.4) mmol/L], and T2DM group [(2.0±1.0) mmol/L] (all P<0.05). (3) The fasting glucose level deteriorated the most rapidly in the IFG group, while it reached the highest postprandial peak in the IFG/IGT group. The blood glucose curve increased along the order of NGT, I-IGT, IFG/IGT, IFG, and T2DM. (4) When the level of glycosylated hemoglobin (HbAlc) level was less than 7%, the fasting phase of curve virtually coincided with each other among individual groups with different HbAlc levels; however, the postprandial peak separated slightly. When the HbAlC level was between 7. 0% and 7.9% , the postprandial peaks of individual groups with different HbAlc levels dispersed markedly. When the HbAlc level was higher than 8% , the fasting blood glucose curve moved upwards significantly with increasing postprandial excursion. Conclusion (1) With the deterioration of glucose regulation, the intraday and day-to-day blood glucose excursions become increasingly fluctuant. (2) The amplitude of glycemic excursion is lower in the NGT group than in the T2DM group, however, the frequency of glycemic excursion is higher in the NGT subject than in the T2DM subjects. The glucose excursion profile of the IGR subjects is between the NGR and T2DM subjects. (3) The characteristics of glucose excursion of the IGT group are similar to those of the T2DM group, and the characteristics of the IFG group are similar to those of the NGT group. (4)The loss of postprandial glycemie control precedes evident deterioration in fasting phase of IGR.

Objective To study the relationship between the glucose fluctuation and β cell function in the diabetes mellitus (DM) patients. Methods Sixty hospitalized DM patients, 27 males and 33 females, aged (59±14), with a course of DM(8±8) years, underwent dynamic blood glucose monitoring by continuous glucose monitoring system (CGMS). Arginine stimulation test was conducted to detect the blood glucose and C peptide. Blood lipids were measured by automatic chemistry analyzer . The relations among fast plasma glucose (FPG), glycated hemoglobin (HbAlc), mean glucose concentration (MBG), mean amplitude of glycemic excursion (MAGE), and incremental value of C peptide (△CP) were studied. Results (1)The subjects were divided into five subgroups by HbAlc, 24 h CGMS profiles showed that a progressive deterioration of the glycemic profiles from group 1 to 5 associated with increasing levels of HbAlc. The FPG levels were not significantly different between the group of HbAlc <6.5% ,and the group of 6.5% ≤HbAlc <7%, but the postprandial blood glucose of the latter group was higher than that of the former group. The CGMS curve shifted upward along with the increase of HbAlc level. (2) After adjustment for sex, age, and diabetes duration, positive correlation was found between HbAlcw and FPG, MBGw and FPG, MBG and HbAlc , MAGE and HbAlc, and MBG and M AGE (r=0.67,0.66,0.63,0.44,0.39, all P <0.01) ,and FPG and MAGE(r=0.31, P<0.05). (3) After adjustment for sex, age, and diabetes duration, the △CP was negatively correlated with FPG, HbAlc and MAGE (r=-0.30, P<0.05;r=-0.39, -0.42, all P<0.01). MBG was not significantly correlated with △CP (P>0.05). (4) There was no significant differences in the △CP level when HbAlc < 7% , but decreased when HbAlc≥7%. (5) Stepwise regression analysis demonstrated that MAGE firstly entered the equation and △CP was predicted by MAGE, total cholesterol, and HbAlc when △CP was regarded as dependent variable and age, diabetic duration, BMI, waist-to-hip ratio, blood pressure, MBG, MAGE, FPG, HbAlc, and blood lipid were regarded as independent variable (adjusted R2=0.305, P<0.01). Conclusion Glucose fluctuation deteriorates the β cell function much more than sustained hyperglycemia does.

Objective To evaluate the characteristics of daily glucose change, insulin sensitivity, and insulin release in polycystic ovary syndrome (PCOS) women with normal glucose tolerance. Methods Oral glucose tolerance test (OGTY) with 75 g glucose was conducted on 20 PCOS women with normal glucose tolerance and 20 age-matched healthy women with normal menstruation. Before the glucose uptake and 30, 60, and 120 min after samples of venous blood were collected to detect the blood glucose and insulin. Continuous glucose monitoring system (CGMS) was used to monitor the glucose concentration of subcutaneous interstitial fluid so as to reflect the blood glucose level. Mean blood glucose level (MBG) and its standard deviation (SDBG), mean amplitude of glycemic excursion (MAGE), peak level of postprandial plasma glucose as well as its peaking time during a 48-hour period CGMS were calculated. Stumvoll first-phase and second-phase (1st PH and 2nd PH) insulin release during OGTT were evaluated by Stumvoll formula, whereas baseline insulin release by HOMA-B. Insulin sensitivity index (ISI) was evaluated by Cederhom formula. Results (1) The 1-hour and 3-hour plasma glucose levels during OGTT of the PCOS group were higher than those of the control group (P<0.01 and P <0.05 respectively). The fasting insulin level and insulin levels 30, 60,120, and 180 min after the glucose uptake during OGTT of the PCOS group were all significantly higher than those of the control group (all P<0.01). (2) The daily MBG, SDBG, and MAGE of the PCOS group were (5.43±0.44), (0.66±0.24), and (1.46±0.47) mmol/L respectively, all similar to those of the control group [(5.3±0.5 ), (0.67±0.27), and (1.7±0.7) mmol/L respectively, all P>0.05]. The peaking time of post-breakfast plasma glucose level of the PCOS group was (40±18) min, significantly longer than that of the control group [(30±10) min, P<0. 05]. (3) The ISI of the PCOS group was 64 (59-81), significantly lower than that of the control group [95(78 -102), P<0.01]. The Stumvoll 1st PH and 2nd PH insulin release levels of the PCOS group were 1779 (1411-2194) mU/L and 440 (361-545) mU/L respectively, both significantly higher than those of the control group [1217 (1056-1477) and 320 (283-375) mU/L respectively, P<0.01 and P<0.05]. Conclusion With normal glucose tolerance, the PCOS women show (1) a backwardly-shifted peak of glucose -stimulated insulin secretion, (2) an abnormal mode of daily glucose change characterized by a delayed peak of post-breakfast plasma glucose level, and (3) significant decrease of peripheral insulin sensitivity with compensated increase of insulin secretion.

Objective To investigate the characteristics of glycemic stability in the first-degree relatives of type 2 diabetes mellitus (T2DM) patients by continuous glucose monitoring system (CGMS). Methods Twenty-two first-degree relatives (FDRs) of T2DM patients and 28 age and gender-matched controls underwent CGMS to obtain the mean blood glucose (MBG) , standard deviation of MBG (SDBG), mean of daily differences (MODD), and mean amplitude of glycemic excursions (MAGE). Oral glucose tolerance test (OGTT) was conducted. Blood glucose, serum lipids, and serum insulin were assayed. The insulin sensitivity and resistance was assessed by HOMA-β, HOMA-IR, △I30/△G30 and modified β cell function index (MBCI). Results There were no significant differences between the FDR and control groups in the levels of plasma glucose in OGTT, MBG, SDBG, and MOOD. However, the MAGE level of the FDR group was (2.3±0.5) mmol/L, significantly higher than that of the control group [(2.0±0.6) mmol/L, P<0.05]. The MBCI level of the FDR group was 17.6 (16.9-50.0), significantly lower than that of the control group [36.0 (15.7-59.6), P<0.05]. There were no significant differences in the serum lipids profile, body fat distribution, HOMA-β, HOMA-IR, and △I30/△G30 between these two groups. Conclusion The excursion of blood glucose is greater in the FDRs of T2DM patients. CGMS is more sensitive to discover such change than OGTT.

Objective To investigate the effect of glucose excursion on oxidative stress that is expressed by plasma 8-isu prostaglandin F2α (8-iso) level. Methods Continuous glucose monitory system (CGMS) was used to calculate the mean amplitude of glycemic excursion (MAGE), mean blood glucose (MBG) and its standard deviation (SDBG), mean 1 h preprandial glucose value (1 h-prePG) and 3 h post-prandial glucose value (3 h PPG) over 24 h period, area under the ROC curve when the blood glucose within 24 h > 5.6 mmol/L (AUC 5.6), mean of daily differences (MODD), and mean postprandial glucose excursion (MPPGE) on 33 individuals with normal glucose regulation (NGR), 25 subjects with impaired glucose regulation (IGR), and 25 patients with newly diagnosed type 2 diabetes mellitus (T2DM) for 3 days. Plasma 8-iso level was determined by EIA. Results The plasma 8-iso level of the T2DM patients was 230 ng/L, significantly higher than that of the subjects with IGR (199 ng/L, P<0.05) and that of the NGR subjects (156 ng/L, P<0.01). Patients with T2DM also had higher levels of glycated hemoglobin (HbAlc), MBG, SDBG, 1 h pre-PG and 3 h PPG, MAGE, and MODD than those of the NGR and IGR subjects (P<0.05 or 0.01). The plasma 8-iso level and parameters of glucose excursion of the IGR subjects were all significantly higher than those of the NGR individuals (P<0.05 or 0.01) . Plasma 8-iso level was positively correlated with MAGE, MBG, SDBG, 1 h pre-PG, 3 h PPG, MODD, and HbAlc in all groups. Further analysis showed that the relationship between plasma 8-iso level and MAGE remained significant after adjustment for the other parameters of glucose excursion in multiple linear regression analysis (multiple R2=0.55 for the model including MAGE). Standardized regression coefficients were 0.694 (P=0.000) for MAGE. Conclusion Glucose excursion exhibits a stronger triggering effect on oxidative stress than chronic sustained hyperglycemia in the subjects with IGR and T2DM.

Clinical data A 61-year-old female was admitted to the hospital due to "pain in the left head and face for 3 months and visual acuity decreased in the left eye for 1 month". Three months ago, the patient suffered dull pain in the top of the left head after "cold", which was aggravated paroxysmally, accompanied by nasal congestion, and sometimes a small amount of dark yellow discharge.

Objective To evaluate the short-term effects and toxicity of vinorelbine combined with cisplatin (NP) as a neoadjuvant chemotherapy regimen in treatment of operable breast cancer non-responsive to the combination of anthraxcyclines and taxans. Methods Nineteen breast cancer patients, all female, who failed to achieve complete remission (CR) or partial remission (PR) to the combination of anthracyclines and taxans as neoadjuvant regimen were treated with 2 cycles of NP regimen (vinorelbine 25 mg/m2, on days 1 and 8 and cisplatin 70 mg/m2, on days 1 and 3, both by intravenous infusion, as a cycle). The clinical objective response was evaluated with dynamic contrast-enhanced MRI of the breast before operation and the pathological response was evaluated by pathological examination. The toxicity of the NP regimen was evaluated according to National Cancer Institute- Common Toxicity Criteria v. 3.0. Results The CR + PR rate of the NP regime was 52.6% (10/19), and pathological response (G2+G3+G4+G5) was found in 17 cases (89.5%, 17/19). The most common toxicities were neutropenia and nausea/vomiting. These toxicities were reversible and did not cause death. Conclusion A well-tolerated and effective regimen for breast cancer patient who fail to respond to the combination of anthracyclines and taxans neoadjuvant chemotherapy, the NP regimen can be considered as an effective choice of second-line regimen. It can be considered as an effective choice of second-line regimen.

Objective To analyze the difficulty in diagnosis of pituitary hyperplasia secondary to primary hypothyroidism and reasons of misdiagnosis. Methods Ten patients with clinical manifestations of primary hypothyroidism, 3 males and 7 females, aged 7 -26, underwent MR imaging and serum hormone examination before and after thyroid hormone replacement therapy. Tl-weighted images without and with contrast material enhancement in sagittal and coronal planes were obtained. Serum free triiodothyronine, free thyroxine, thyrotropic-stimulating hormone and prolactin (PRL) levels were measured. Results Obvious symmetrical enlargement of the pituitary gland with homogeneous signal intensity was revealed by MRI in all the patients. The height of the pituitary ranged 1.2- 2.2 cm. The pituitary glands appeared homogeneously enhanced after Gd-DTPA administration. After 3-6 months of L-thyroxin replacement therapy, follow-up MRI showed that the pituitary glands reduced in size markedly in 9 cases, and the plasma thyroxine, TSH, and PRL levels of these 9 cases turned normal. One patient was misdiagnosed as with macroadeuoma and was treated with gamma knife, resulting in permanence hypothyroidism. Conclusion Symmetrical enlargement of pituitary gland with homogeneously enhancement on MRI has great diagnostic value in pituitary hyperplasia with primary hypothyroidism. Thyroid hormone replacement therapy can cause regression of the enlarged pituitary, thus avoiding unnecessary surgery.

Objective To invesigate the molecular pathogenesis of deafness among the youth by means of genetic testing so as to provide pre-marriage genetic counseling and instruction for the deaf youth. Methods 217 deaf young people, 126 males and 91 females, aged 18.9(16-26), from Yunnan and Guizhou provinces, underwent history taking, auditory testing, and collection of peripheral blood samples. Genomic DNA and mitochondrial DNA were extracted to undergo sequence analysis of the entire gene GJB2, common point mutation of SLC26A4 gene, and mutation of mtDNA A1555G. Genetic prediction and marriage instruction were provided to each subject based on these results. Results Twenty-three of the 117 persons (10.5%) , 13 males and 10 females, were mtDNA A1555G mutation carriers and they were instructed that they, their maternal relatives, and the offspring of the female carriers, should they be born, should stricdy avoid the administration of amino glycoside antibiotics. Twenty eight of the 115 persons (12.9%), were confirmed to carry homozygous or compound GJB2 mutations, 5 individuals (2.3%) carried heterozygous GJB2 mutation, 19(8.8%) carried homozygous or compound SLC26A4 mutations, and one (0.5%) carried heterozygons SLC26A4 mutation. The suggestion for them was to avoid getting married with deaf partners caused by the same deaf gene or with individuals carrying mutations in the same deaf gene. Meanwhile, suggestions such as avoiding aggressive exercises and head injury were provided to the deaf young people with SLC26A4 mutations. Conclusion Genetic testing can provide more accurate and useful genetic counseling and instruction to deaf young people for their partner selection and eugenics.

Objective To investigate the T cell proliferative response and antibody formation to citrullinated collagen type Ⅱ ( Cit-C Ⅱ) in patients with rheumatoid arthritis (RA), and explore whether autoreactive T cells responding to Cit-C Ⅱ plays a role in the pathogenesis of RA. Methods Arginine residues of bovine collagen type Ⅱ (C Ⅱ) were converted to citrulline residues by peptidylarginine deiminase (PAD). Peripheral blood samples were collected from 34 RA patients, and 18 sex- and age-matched controls, including 6 osteoarthritis patients and 12 healthy blood donors. Peripheral blood mononuclear cells (PBMCs) were isolated and cultured with Cit-C Ⅱ, C Ⅱ, or fetal bovine serum RPMI 1640 fluid, phytohemagglutinin (PHA), or citrullinated buffer as controls. Cellular reactivity levels against Cit-C Ⅱ and C Ⅱ were investigated by measuring the proliferation of PBMCs to calculate the stimulation index (SI). ELISA was used to detect the presence of antibodies against Cit-C Ⅱ and C Ⅱ. Results The positive rate of T cell proliferative response to Cit-C Ⅱ of the RA group was 32.4% (11/34), significantly higher than that of the control group (0,P<0.05). The positive rate of T cell proliferative response to C Ⅱ of the RA group was 35.3% (12/34), significantly higher than that of the control group (11.1%, P<0.05). Interestingly, Cit-C Ⅱ could not elicit a better T cell proliferative response than C Ⅱ did. In the RA patients, the anti-Cit-C Ⅱ antibody positive rate was 52.9% (18/34), significantly higher than that of the anti-C Ⅱ antibody positive rate [32.4% (11/34), P<0.05). The serum IgG anti-C Ⅱ antibody positive rate of the patients with positive T cell responses to C Ⅱ was 58.3% (7/12), significantly higher than that of the patients with negative T cell responses to C Ⅱ [18.2% (4/22), P <0.05]. The serum lgG anti-C Ⅱ antibody positive rate of the patients with positive T cell responses to Cit-C Ⅱ was 72.7% (8/11), significantly higher than that of the patients with negative T cell responses to Cit-C Ⅱ [43.5% (10/23), P<0.05]. Conclusion The recognition of Cit-C Ⅱ by circulating IgG antibodies is a RA-specific serological phenomenon. The formation of C Ⅱ antibody in the RA patients may be related to B cell activation mediated by C Ⅱ specific T cells. The role of Cit-C Ⅱ in RA cellular immune need be further studied.

Objective To study the nephrotoxicity tacrolimus (FK506) at the therapeutic dose the preventive effect of diltiazem (Dil), a calcium antagonist against the FK506-induced pathological changes. Methods 24 Sprague-Dawley male rats were randomly divided into 4 equal groups: cyclosporine A (CsA) group, undergoing treatment of CsA at the therapeutic dose after kidney transplantation (25 mg·kg-1·d-1) for 4 weeks, FK506 group treated with FK506 (0.8 mg·kg1·d-1), FK506 + Dil group treated with FK506 (0.8 mg·kg-1·d-1) and Dil at the dose of 8 mg·kg-1·d-1, and control group. Four weeks later body weight was measured and 24 h urine sample was collected. Then the rats were killed. Their kidneys underwent light and transmission electron microscopy. Results The body weight ad weight gain, and the weights of both kidney of the CsA group were all significantly lower than those of the other 3 groups (all P<0.05), and there were not significant differences in there parameters among the other 3 groups. The serum creatinine levels of the FK506 and CsA groups were (36.0±2.6) and (34.2±4.5) μmol/L respectively, both significantly higher than those of the FK506 + Dil and control groups [(28.5±2.1) and (29.2±3.428)μmol/L respectively, all P<0.05], however, there was no significant difference between the FK506 + Dil and control groups. The creatinine clearance rate of the FK506 and CsA groups were (0.63±0.45) and (0.58±0.39)ml·min-1·100 g-1 respectively, significantly lower than those of the FK506 + Dil and control groups [(1.55±0.91) and (1.02±0.62) ml·min-1·100 g-1 respectively, all P<0.05]. Pathological examination showed epithelial cell cloudy swelling and vaeuolization and interstitial fibrosis in the renal tubules, mitochondria swelling and vacuolization in renal tubular epithelial cells, renal arteriole hyalinization, and foot cell conjugation glomerulus, mitochondria swelling and vacuolization in the FK506 and CsA groups, and such changes were relatively mild in the FK506 + Dil group. Conclusion FK506 at renal transplantation therapeutic dose, as well as CsA, induces pathological changes in renal tissues and ultrastructural organization. Dil is able to prevent FK506-induced these pathological changes.

Objective To investigate the therapeutic effects of emodin on acute cholestatic hepatitis and mechanism thereof. Methods 96 SD rats were randomly divided into 4 groups to be treated with emodin, ursodeoxycholic acid, dexamethasone, or normal saline respectively for 4 days. On the 5th day gastric perfusion of alpha-naphthylisothiocyanate (ANIT) was performed to establish models of cholestatic hepatitis. 4-6 hours after the establishment of model the above mentioned agents were given continuously. 24, 48, and 72 hours after the model establishment blood samples were collected from abdominal aorta to examine the total bilirubin (TB), direct bilirubin (DB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyhransferase (GGT), and total bile acid (TBA). Specimen of liver was collected to undergo pathological examination. PCR was used to detect the mRNA expression of cytokine-induced neutrophil chemoattractant 1 (CINC-I) and macrophage inflammatory protein 2 (MIP-2), and Western blotting was used to detect the protein expression of intercellular adhesion molecule 1 (ICAM-1) . Twenty-four rats treated with NS only were used as controls. Results The pathological changes of behaviors and liver of the emodin and ursodeoxycholic acid groups were all remarkably milder than those of other model groups. The levels of TB [(32.8±3.7) μmol/L, (61.0±16.4) μmol/L, (10.8±4.5) μmol/L], DB[(26.03±3.10) μmol/L, (49.40±18.16)μmol/L, (8.04±3.03) μmol/L], and ALT [(314±50) U/L, (664±97)U/L, (200±60) U/L], at the time points 24, 48, and 72 hours, the 48 and 72 hours AST levels, the 48 hours ALP level, the 72 hours GGT level, and the 48 and 72 hours TBA levels of the emodin group were all significantly lower than those of the model group (all P<0.05). The 24 and 48 hours TB levels, 24 hours DB and ALT,and 24,72 hours TBA levels of the emodin group were all significantly lower than those of the ursodeoxycholic acid group (all P<0.05). The 24,48 hours TB and TBA levels, and the ALT,AST and GGT levels at all time points of the emodin group were all significantly lower than those of the dexamethasone group (all P<0.05). The CINC-1 and MIP-2 mRNA expression levels and ICAM-1 protein expression levels at all time points of the emodin group were all significantly lower than those of the model group (all P<0.05). Conclusion Decreasing the levels of TB, DB and ALT in particular, emodin has a protective effect on cholestatic hepatitis. Its effects are quicker than ursodeoxycholic acid, and it has better effects on ALT, AST GGT, and TBA than dexamethasone . These effects may be due to inhibition of the activation of CINC-1, MIP-2, and ICAM-1.

Objective To investigate the influences of glutamine (Gln) on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in hepatocytes activated by interleukin (IL)-1β, a pro-inflammatory cytokine. Methods Primary hepatocytes were isolated from SD rats by in situ collagenase perfusion, and cultured with normal saline (NS), IL-1β(1 nmol/L) alone, IL-1β(1 nmol/L) with Gln of 2,5, or 10 mmoL/L for 24 hours. The concentration of NO in the supernatant was detected by biochemical method. Western blotting and real-time quantitative reverse transcription PCR (RT-PCR) were used to detect the protein and mRNA expression of iNOS in the hepatocytes. The binding activity nuclear factor kappa B (NF-κB) in hepatocytes cellular localization of nuclear factor kappa B (NF-κB) in the nuclei of hapatocytes was investigated using electrophoretic mobility shift assay (EMSA). Results The average NO concentration of the IL-1κ group was 72.7 μmol/L, significantly higher than that of the NS group [(41.7) μmol/L, P<0.01]. The NO concentrations in the supernatant of the IL-1β+ Gln 5 and 10 mmol/L groups were 52.9 and 44.4 μmol/L respectively, both significantly higher than that of the NS group (both P<0.05). The iNOS mRNA and protein expression levels of the IL-1μ group were 11 and 2.5 times as those of the NS group (both P<0.05). Gln dose-dependently decreased the iNOS mRNA and protein expression levels in the hepatocytes. The NO concentration and levels of iNOS mRNA and protein expression in the hepatocytes of the Gln 10 mmol/L group were not significantly different from those of the NS group. The NF-κB levels in the nuclei of hepatocytes of the IL-1β group, 3 IL-1β + Gln group, and only Gln group were all higher than that of the NS group. Conclusion Glutamine down-regulates the iNOS gene over-expression mediated by IL-1βin hepatocytes through an NF-κB independent pathway.

Objective To study the chiral selectivity in vascular endothelial differentiation in drug resistant lung cancer cells induced by high-dose L- or D-methotrexate (MTX) enantiomer. Methods Human lung cancer cells of the line A549 were co-cultured with high-dose (15 μmol/L) L- or D- MTX enantiomer so as to develop cancer cells resistant to MTX. MTT method was used to detect the drug resistant index. Flow cytometry was used to detect the expression of CD44, a transmembrane glycoprotein reflecting the migration ability of cells, CD31, a marker of vascular endothelium, and P-170 protein. Fifteen BALB/c nude mice were inoculated with the parent A549 cells, L-MTX-resistant A549 cells induced by L-MTX enantiomer, and D-MTX-resistant A549 cells induced by D-MTX enantiomer. Four weeks later the mice were killed to take out the tumor masses, Immunohistochemistry with CD34 staining was used to detect the microvascular density (MVD). Results The drug resistant index of the D-MTX induced drug resistant A549 cells was 20.1±2.3, significantly higher than that of the L-MTX-induced cells (12.4±1.2, P=0,000). The CD44 positive rate of the D-MTX induced A549 cells was 97.0%±0.9%, not significantly different from that of the L-MTX-induced A549 cells (96.7%±1.4%, P=0.544). The CD31 positive rate of the D-MTX induced A549 cells was 91.9%±3.2%, significantly higher than that of the L-MTX-induced A549 cells (32.9%±8.0%, P=0.000). The P-170 protein positive rate of the parent cells was 85.5%±4.6%, and the P-170 protein positive rate of the D-MTX-induced A549 cells was 87.0%±8.9%, significantly higher than that of the L-MTX-induced cells (71.5%±8.2%, P=0.002). The MVD of the D-MTX-indueed cells was 55.9±11.9, significantly higher than that of the L-MTX-induced cells (7. 2±1.7, P=0.000). MVD was significantly positively correlated with the CD31 level (r=0.462, P=0.007), and not correlated with P-170 protein and CD34 levels. Conclusion The MTX enantiomers have different chiral selectivity on human lung cancer cell, D-MTX resistant cells shows a potential of differentiation from cancer cells to vascular endothelial cells. D-MTX is not be regarded just as a pollutant in the drug MTX, MTX with single enantiomer (L-MTX) should be selected clinically so as to decrease the side effects of D-MTX.

Objective To investigate the spatio-temporal expression of connexin (Cx) 40 and Cx45 genes in Cx43 knockout embryonic mouse hearts. Methods Cx43 knockout heterozyguus mice were raised. PCR was performed to identify genotypes of their offsprings. The homozygote (Cx43 -/-) was used for study and the wild type (Cx43 +/+) was used as control. Immuno-histoehemistry was used to detect the Cx40 and Cx45 expression in different parts of the fetal hearts at the embryonic days (EDs) 10.5, 11.5, 12.5, 13.5, 14.5, and 15.5, respectively. SCIM microscopic image analytic system was used for quantitative analysis of staining intensity. Results (1) Cx40 expression was detected in ventricles of Cx43 +/+ fetal heart as early as ED10. 5 with the intensity represented by A value of 8.6. Subsequently it was distributed in the atria and ventricles with the peak expression observed at ED14.5 (A value=94.8), and faded afterwards. Less Cx40 expression was observed in the Cx43 -/- fetal hearts as compared with Cx43 +/+ although its expression pattern was similar in both groups. (2) Cx45 expression was detected in ventricles at ED 10.5(A value =20.0). It was subsequently distributed in the atria and ventricles with the peak expression observed at ED12.5 (A value=49.6), and then faded. Less Cx45 expression was observed in the Cx43 -/- fetal hearts as compared with Cx43 +/+ although its expression pattern was similar as well in both groups. Conclusion Down-regulated expression of the genes Cx40 and Cx45 may be associated with the abnormal heart development in Cx43 knockout animals.

A 34-year-old male was admitted to the Second Affiliated Hospital of Zhejiang University Medical College on February 23, 2006 with "two pneumonia" due to fever, cough, chest tightness and shortness of breath after activity for 2 weeks.

Diabetes is a metabolic disease that seriously endangers human health in the 21st century. Genetic, autoimmune and environmental factors are closely related to the occurrence and development of diabetes.

A 63-year-old male was admitted to the hospital on July 4, 2008 due to "14 years after mechanical aortic valve replacement, intermittent fever for 3 months". In 1994, the patient underwent mechanical aortic valve + artificial blood vessel replacement due to aortic dilation and aortic valve insufficiency, and the valve function was normal every year.

A 45-year-old female was admitted to the hospital on July 8, 2008 due to "dull pain in the upper abdomen for 14 days and yellow urine for 7 days". Before 14 days, she developed dull pain in the upper abdomen without obvious inducement, which was tolerable, without radiating pain, nausea and vomiting, diarrhea and abdominal distension, fear of cold and fever, chest tightness and shortness of breath, acid reflux and belching, cough and sputum, and was not diagnosed and treated.

A 26-year-old woman was admitted to the hospital on July 2, 2008 due to cough, hemoptysis and fever for 2 months, aggravated with dyspnea for 1 week. Since May, she had no trigger for cough, hemoptysis and fever, occasional chest tightness, chest pain, shortness of breath and night sweats. She was diagnosed as "acute bronchitis" in the local hospital and was given anti-infective treatment, but the curative effect was not good. One week ago, her symptoms aggravated and she developed dyspnea, with fever reaching 40.3℃, so she went to our hospital for treatment. The outpatient clinic was given anti-infective treatment with "lung infection", but the symptoms continued to aggravate, hemoptysis and inability to lie down, so she was admitted to the hospital.

The corneal senile ring is a lipid deposition in the stroma of the corneal periphery, which has some similarities with the lipid deposition in atherosclerosis. The epidemiological findings about the relationship between the senile ring and coronary atherosclerotic heart disease (CAD) are different.

Previous studies have shown that serum 25-hydroxyvitamin D [D25 (OH) D] levels are negatively correlated with cardiovascular disease (CVD) risk factors, but the relationship between D25 (OH) D levels and CVD epidemiology has not been studied on a large scale in the population.