Dan-gua fang improves glycolipid metabolic disorders by promoting hepatic adenosine 5'-monophosphate activated protein kinase expression in diabetic Goto-Kakizaki rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effect of Dan-gua Fang on adenosine 5'-monophosphate (AMP) activated protein kinase (AMPK) α expression in liver and subsequent improvement of glucose and lipid metabolism.</p><p><b>METHODS</b>Forty 13-week-old diabetic Goto-Kakizaki (GK) rats were randomly divided into model, Dan-gua Fang, metformin and simvastatin groups (n=10 for each), and fed high-fat diet ad libitum. Ten Wistar rats were used as normal group and fed normal diet. After 24 weeks, liver expression of AMPKα mRNA was assessed by real-time PCR. AMPKα and phospho-AMPKα protein expression in liver was evaluated by Western blot. Liver histomorphology was carried out after hematoxylin-eosin staining, and blood glucose (BG), glycosylated hemoglobin A1c (HbA1c), food intake and body weight recorded.</p><p><b>RESULTS</b>Similar AMPKα mRNA levels were found in the Dan-gua Fang group and normal group, slightly higher than the values obtained for the remaining groups (P<0.05). AMPKα protein expression in the Dan-gua Fang group animals was similar to other diabetic rats, whereas phospho-AMPKα (Thr-172) protein levels were markedly higher than in the metformin group and simvastatin group (P<0.05), respectively. However, phosphor-AMPKα/AMPKα ratios were similar in all groups. Dan-gua Fang reduced fasting blood glucose with similar strength to metformin, and was superior in reducing cholesterol, triglycerides, high-density lipoprotein cholesterol as well as improving low-density lipoprotein cholesterol in comparison with simvastatin and metformin. Dan-gua Fang decreases plasma alanine aminotransferase (ALT) significantly.</p><p><b>CONCLUSION</b>Dan-gua Fang, while treating phlegm-stasis, could decrease BG and lipid in type 2 diabetic GK rats fed with high-fat diet, and effectively protect liver histomorphology and function. This may be partly explained by increased AMPK expression in liver. Therefore, Dan-gua Fang might be an ideal drug for comprehensive intervention for glucose and lipid metabolism disorders in type 2 diabetes mellitus.</p>

Research of Dangua Recipe on intervening the glycolipid metabolism and oxidative stress in diabetic rats with atherosclerosis / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the effects of Dangua Recipe (DGR) on glycolipid metabolism, serum reactive oxygen species (ROS) level, nuclear factor kappa B (NF-kappaB) positive expression and its mRNA expression level in the thoracic aorta of diabetic rats with atherosclerosis, thus revealing its partial mechanisms for intervening chronic diabetic complications.</p><p><b>METHODS</b>Recruited 40 Goto-Kakisaki (GK) Wistar rats were fed with high fat forage containing metabolic inhibition Propylthiouracil, and peritoneally injected with endothelial NOS inhibitor N-nitro-L-arginine methyl ester to establish a high fat diabetes model with atherosclerosis. The modeled GK rats were stratified by body weight, and then, by blood glucose level from high to low, randomly divided into the DGR group (at the daily dose of 8 mL/kg), the metformin group (MET, at the daily dose of 150 mg/kg), the simvastatin group (SIM, at the daily dose of 2 mg/kg), and the model group (MOD, fed with pure water, at the daily dose of 8 mL/kg) according to the random number table, 10 in each group. Another 10 Wistar rats of the same ages and comparable body weight level were recruited as the normal control group. All the interventions lasted for 24 weeks by gastrogavage. The fasting blood glucose (FBG) and body weight were monitored. The HbA1c, TC, LDL-C, HDL-C, TG, serum ROS were determined. The aortic NF-kappaB level was analyzed with immunohistochemical assay. The expression of NF-kappaB (P65) mRNA in the aorta was detected with Real-time PCR.</p><p><b>RESULTS</b>The body weight in the normal control group was eventually heavier than others (P < 0.01). There was no difference among the four groups of GK modeled rats (P > 0.05). The FBG in the four GK modeled groups were higher than that in the normal control group (P < 0.01, P < 0.05). There was no statistical difference in the blood glucose level at the first visit and at the baseline among the GK modeled groups (P > 0.05). The last FBG level was obviously lower in the MET and DGR groups than in the MOD group (P < 0.01) and the SIM group (P < 0.05). Twenty-four weeks after intervention, the level of FBG, HbA1c, TC, LDL-C, HDL-C, and NF-kappaB positive expression rate of the thoracic aorta of the four groups of GK modeled rats, and NF-kappaB mRNA expression in the thoracic aorta in the MOD group, the MET group, and the DGR group were significantly higher than those in the normal control group (P < 0.01, P < 0.05). The TG level, serum ROS in the MET, DGR, and SIM groups, and the NF-kappaB mRNA expression level in the thoracic aorta in the SIM group were significantly lower than those in the normal control group (P < 0.01, P < 0.05). The levels of FBG, TC, LDL-C, serum ROS, NF-kappaB mRNA expression level in the thoracic aorta in three drug intervention groups, and NF-kappaB positive expression rate in the DGR and MET groups, and the levels of HbA1c, TG in the DGR group were significantly lower than those in the MOD group (P < 0.01, P < 0.05). The level of FBG in the MET and DGR groups were lower than that in the SIM group (P < 0.05). The level of NF-kappaB mRNA expression in the thoracic aorta of the SIM and DGR groups, and the levels of TC and LDL-C in the DGR group were significantly lower than those in the MET group (P < 0.01).</p><p><b>CONCLUSION</b>DGR played a role in preventing and treating chronic diabetic complications by comprehensively regulating blood glucose and serum lipids, as well as down-regulating oxidative stress.</p>

Association of matrix metalloproteinase-3 gene polymorphisms with subtypes of ischemic stroke / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association between matrix metalloproteinase-3 (MM-3) gene polymorphisms and subtypes of ischemic stroke (IS) in northern Han Chinese population.</p><p><b>METHODS</b>A total of 289 patients with acute IS (within 3 days after the onset, including 185 with large artery atherosclerosis (LAA) and 104 for small artery occlusion (SAO)) and 175 matched healthy controls were recruited for this case-control study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or sequenc-based typing (SBT) was carried out to analyze 3 SNPs of the MMP-3 gene.</p><p><b>RESULTS</b>An incomplete linkage disequilibrium (LD) block was constructed with the 3 SNPs, and the distribution of genotypes of the 3 SNPs differed between the LAA group and controls in a dominant model: Carriers of 5A allele (5A5A+5A6A) of the rs3025058 locus were 1.72 times more susceptible to LAA stroke compared with carriers of 6A6A alleles (P=0.017, OR=1.72, 95% CI: 1.10-2.69), carriers of G alleles (GG+AG) of the rs522616 locus were 0.52 times more susceptible to LAA stroke compared with carriers of AA alleles (P=0.005, OR=0.52, 95% CI: 0.33-0.82), whilst carriers of A allele of the rs679620 locus were 1.55 times more susceptible to LAA stroke compared with carriers of GG alleles (P=0.042, OR=1.55, 95% CI: 1.01-2.37). However, no significant difference has been found between particular genotypes of such SNPs between SAO patients and controls (P> 0.05). Furthermore, 5A-A-A and 6A-A-A haplotypes were significantly more common in LAA group than the controls (P< 0.05), whilst 6A-G-G haplotype has been the opposite (P< 0.01).</p><p><b>CONCLUSION</b>Our study has demonstrated that serum MMP-3 level is significantly increased at acute stage of LAA as well as SAO type strokes. There may be an association of rs3025058, rs522616 and rs679620 of MMP-3 gene with susceptibility to LAA stoke in northern Han Chinese population.</p>

Correlation study of CXCL16 gene rs3744700 polymorphisms and cerebral infarction subtypes / 中国脑血管病杂志

Objective: To study the correlation between the serum chemokine CXC Ligand 16 (CXCL16) levels or the CXCL16 gene rs3744700 polymorphisms and TOAST subtypes in patients with acute cerebral infarction. Methods: A total of 248 patients with atherosclerotic cerebral infarction within 7 days after symptom onset were selected, among them 149 patients were in a large artery atherosclerotic (LAA) cerebral infarction group, and 99 patients were in a small arterial occlusive (SAO) cerebral infarction group. The polymerase chain reaction (PCR) and gene sequencing were used to detect the genotypes. An enzyme-linked immunosorbent assay was used to detect the serum CXCL16 levels. Results: Circled digit oneSerum CXCL16 level in the LAA cerebral infarction group was 2.5 ± 0.3 μm/L and in the SAO cerebral infarction group were 2.3 ± 0.6 μg/L (P<0.01). Circled digit twoAmong the 149 patients in the LAA cerebral infarction group, the GG genotype frequency at polymorphic loci of CXCL16 gene rs3744700 was 91.9% (137/149) and the G allele frequency was 96.0% (286/298). They were higher than 81.8% and 89.9% in the SAO cerebral infarction group. There were significant differences (P < 0.05). Circled digit threeThe serum CXCL16 level in patients with CG genotype was 2.5 ± 0.3 μg/L in the LAA cerebral infarction group, ant it was higher than 2.1 ± 0.3 μg/L in patients with GT + TT genotype; the serum CXCL16 level in patients with CG genotype was 2.4 ± 0.6 μg/L in the SAO cerebral infarction group, and it was higher than 2.1 ± 0.3 μg/L in patients with GT + TT 2 genotype (all P < 0.01). Among the patients with GG genotype, the serum CXCL16 level in the LAA cerebral infarction group was higher than that in the SAO cerebral infarction group (P = 0.01); there was no significant difference in patients with GT + TT genotype between both groups. Circled digit fourMultivariate Logistic regression analysis showed that the serum CXCL16 level (OR =0.37, 95% CI 0.19 -0.70) and the GG genotype at polymorphic loci of CXCL16 gene rs3744700 (OR =2.57, 95% CI 1.23 -5.36) were the independent risk factors for affecting LAA cerebral infarction. Conclusion: In the TOAST subtypes, the correlation of serum CXCL16 level and the GG genotype at polymorphic loci of CXCL16 gene rs3744700 and LAA cerebral infarction are higher than SAO cerebral infarction.

Changes of regulatory T cells and FoxP3 gene expression in the aging process and its relationship with lung tumors in humans and mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Immunosuppressive regulatory T cells (Tregs) participate in tumor immune evasion and the number and suppressive function of Tregs change with the aging process, but it is not clear whether such change leads to a higher incidence of tumors in the elderly. To this end, we designed experiments to explore the changes of Tregs and the functional gene Forkhead box P3 (FoxP3) in the aging process and its relationship with lung tumors in humans and mice.</p><p><b>METHODS</b>The percentage of CD4(+)CD25(+)CD127(low) Tregs and expression of FoxP3 mRNA were analyzed using flow cytometry (FCM) and real-time fluorescence-based quantitative polymerase chain reaction (FQ-PCR). Markers were analyzed in the peripheral blood (PB) of 65 elderly patients (age ≥ 65 years) with primary non-small cell lung cancer (NSCLC), 20 younger patients (aged < 55 years) with NSCLC, 30 elderly healthy individuals and 30 young healthy individuals. Furthermore, we set up the Lewis lung cancer model with C57BL/6 female mice. Thirty-six mice were divided into a young healthy group, a middle-aged healthy group, an elderly healthy group, a young tumor group, a middle-aged tumor group, and an elderly tumor group. The percentage of CD4(+)CD25(+)FoxP3(+) Tregs and the expression level of FoxP3 mRNA in splenocytes were determined in the six groups.</p><p><b>RESULTS</b>The percentage of peripheral CD4(+)CD25(+)CD127(low) Tregs and the expression of FoxP3 mRNA were significantly increased in elderly patients with NSCLC comparing with the other groups and in elderly healthy individuals compared with young healthy individuals. Further analysis showed that the percentage of CD4(+)CD25(+)CD127(low) Tregs and the expression of FoxP3 mRNA were closely associated with tumor node metastasis (TNM) staging in elderly patients with NSCLC. In the mouse model, the percentage of CD4(+)CD25(+)FoxP3(+) Tregs and the expression of FoxP3 mRNA in splenocytes of the tumor groups were significantly higher than in the healthy groups, with the highest expression in the elderly tumor group. In the healthy groups, the elderly healthy mice had the highest percentage of Tregs and expression of FoxP3 mRNA. The elderly mice had larger and heavier tumors than did the young and middle aged mice.</p><p><b>CONCLUSIONS</b>The up-regulation of Tregs and the FoxP3 gene with aging may play an essential role in oncogenesis and development of lung tumors in an elderly population.</p>

Extra-anatomic bypass for complex aortic coarctation in adults / 中华外科杂志

<p><b>OBJECTIVE</b>To demonstrate an effective operation of extra-anatomic bypass for complex aortic coarctation in adults.</p><p><b>METHODS</b>Between July 1997 and October 2010, 51 patients underwent extra-anatomic aortic bypass. There were 39 male and 12 female patients. Mean age was (40 ± 14) years (ranging from 18 to 63 years). Operative technique of extra-anatomic bypass consisted of performing an ascending-to-descending or abdominal or femoral aorta bypass (8, 39 and 4 patients). Concomitant procedures were performed in 38 patients: 10 isolated aortic valve replacements (AVR), 11 aortic root replacements (Bentall), 4 ascending aorta replacements including 3 concomitant AVR, 5 mitral valve replacements including 3 concomitant AVR, 4 ventricular septal defect correcting with AVR, and 4 coronary artery bypass graft.</p><p><b>RESULTS</b>Mean follow-up time was (30 ± 9) months (ranging from 5 to 60 months). Two patients were reoperated for hemorrhage in descending aorta anastomosis, one of whom was dead of multiple organ failure in perioperative period. Upper-extremity blood pressure after coarctation correction with extra-anatomic aortic bypass was significantly improved (< 10 mmHg, 1 mmHg = 0.133 kPa). Arterial hypertension was well improved, except 10 patients controlled with less drug therapy. All grafts were patent without obstruction or pseudoaneurysm formation in the follow-up period evaluated by vascular ultrasound and computed tomographic angiogram.</p><p><b>CONCLUSION</b>Extra-anatomic aortic bypass is a safe and effective option for complex aortic coarctation in adults.</p>

Altered CD28 and CD95 mRNA expression in peripheral blood mononuclear cells from elderly patients with primary non-small cell lung cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The expression of the co-stimulatory molecule CD28 and death receptor CD95 on T cells, which change with age, are considered as important immunological parameters of immunosenescence. It is well established that CD28 and CD95 are associated with tumorgenesis and tumor progression, but the relationship between the age-related changes of these two immunological markers and cancer in the elderly is largely unknown.</p><p><b>METHODS</b>The levels of CD28 and CD95 mRNA in peripheral blood mononuclear cells (PBMCs) from sixty-three elderly patients (aged > or = 60 years) with primary non-small cell lung cancer (NSCLC) were analyzed by real-time fluorescence-based quantitative polymerase chain reaction (FQ-PCR). In addition, twenty young patients (aged < 60 years) with NSCLC, thirty elderly healthy donors and thirty young healthy donors were enrolled as controls.</p><p><b>RESULTS</b>CD28 mRNA levels were significantly lower and CD95 mRNA levels were significantly higher in elderly patients with NSCLC than in the other groups. Similar results were found in elderly healthy donors comparing with young healthy donors. By Logistic regression analysis an increased risk of NSCLC was markedly associated with aging, down-regulation of CD28 mRNA and up-regulation of CD95 mRNA, and CD28 mRNA had an obvious negative correlation with the CD95 mRNA. In addition, the mRNA levels of CD28 and CD95 in the peripheral blood of the elderly patients was closely associated with the tumor node metastasis (TNM) stages, grade of cell differentiation and lymph node metastasis status, but not related to pathological types.</p><p><b>CONCLUSIONS</b>The results suggest a close relationship between T cell senescence and NSCLC tumour progress in the elderly, and that up-regulation of CD28 mRNA or down-regulation of CD95 mRNA in peripheral blood T cells may play an important role in inhibiting oncogenesis and development of primary NSCLC in the elderly.</p>

Aike mixture has good anti-inflammatory and analgesic effects on mice / 中华男科学杂志

<p><b>OBJECTIVE</b>To study the anti-inflammatory and analgesic actions of Aike Mixture (AKM).</p><p><b>METHODS</b>A total of 100 male mice were randomly assigned into 5 groups: a normal control group, a drug control group (a hydrocortisone subgroup and an atropine subgroup), a high-dose AKM group, a mid-dose AKM group and a low-dose AKM group. Xylene was spread on the left ear of the experimental mice to induce inflammation, and 1% acetic acid solution injected into the abdominal cavity to produce pain so as to cause the body bend. Different doses of AKM were given and their actions observed.</p><p><b>RESULTS</b>AKM had obvious anti-inflammatory effect on the xylene-induced ear tumefaction and inhibited the pain-caused body bend in the AKM groups, with significant difference from the normal control (P < 0.01).</p><p><b>CONCLUSION</b>AKM has good anti-inflammatory and analgesic effects, which is of clinical significance in the treatment of chronic prostatitis.</p>

A linkage between beta-fibrinogen gene -148C/T polymorphism and cerebral infarction / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the linkage between -148C/T polymorphism of beta-fibrinogen gene and plasma fibrinogen levels in patients with acute cerebral infarction.</p><p><b>METHODS</b>One hundred and fifty-one patients with cerebral infarction and 101 healthy individuals were enrolled in this trial. The beta-fibrinogen gene -148C/T polymorphism was analyzed by PCR-restriction fragment length polymorphism, and plasma fibrinogen levels were obtained from prothrombin time assay.</p><p><b>RESULTS</b>Plasma fibrinogen levels of patients were significantly higher than those of controls (P<0.01). In both groups, T allele carriers had higher plasma fibrinogen levels than other those did (P<0.01); and the fibrinogen level difference was still significant if both groups was based on their sex (P<0.05). Divided by age, each group of the study cases has significant difference between two genotypes (P<0.05). T -148 allele frequency of the middle age case in study group was higher than that in control group (P<0.05).</p><p><b>CONCLUSION</b>High plasma fibrinogen level is a risk factor to cerebral infarction. Plasma fibrinogen level is affected by -148C/T polymorphism of beta-fibrinogen gene. With or without other risk factors and environmental factors affecting, T allele increases plasma fibrinogen level and may be a heritable risk factor to cerebral infarction.</p>