Paradox of using intensive lowering of blood glucose in diabetics and strategies to overcome it and decrease cardiovascular risks / 中国结合医学杂志

Hyperglycemia significantly increases the risk of cardiovascular disease (CVD) in diabetics. However, it has been shown by a series of large scale international studies that intensive lowering of blood glucose levels not only has very limited benefits against cardiovascular problems in patients, but may even be harmful to patients at a high risk for CVD and/or poor long-term control of blood glucose levels. Therefore, Western medicine is faced with a paradox. One way to solve this may be administration of Chinese herbal medicines that not only regulate blood glucose, blood fat levels and blood pressure, but also act on multiple targets. These medicines can eliminate cytotoxicity of high glucose through anti-inflammatory and anti-oxidant methods, regulation of cytokines and multiple signaling molecules, and maintenance of cell vitality and the cell cycle, etc. This allows hyperglycemic conditions to exist in a healthy manner, which is called "harmless hyperglycemia" Furthermore, these cardiovascular benefits go beyond lowering blood glucose levels. The mechanisms of action not only avoid cardiovascular injury caused by intensive lowering of blood glucose levels, but also decrease the cardiovascular dangers posed by hyperglycemia.

Effect of dangua recipe on glycolipid metabolism and VCAM-1 and its mRNA expression level in Apo E(-/-) mice with diabetes mellitus / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect of Dangua Recipe (DGR) on glycolipid metabolism, vascular cell adhesion molecule-1 (VCAM-1) and its mRNA expression level of transgenic Apo E(-/-) mouse with spontaneous atherosclerosis, thus revealing its partial mechanism for curing diabetes mellitus (DM) with angiopathy.</p><p><b>METHODS</b>Diabetic model was prepared by peritoneally injecting streptozotocin (STZ) to Apo E(-/-) mouse. Totally 32 modeled mice were stratified by body weight, and then divided into 4 groups referring to blood glucose levels from low to high by random digit table, i.e., the model group (MOD, fed with sterile water, at the daily dose of 15 mL/kg), the DGR group (fed with DGR at the daily dose of 15 mL/kg), the combination group (COM, fed with DGR at the daily dose of 15 mL/kg and pioglitazone at the daily dose of 4.3 mg/kg), and the pioglitazone group (PIO, at the daily dose of 4.3 mg/kg), 8 in each group. Another 8 normal glucose C57 mouse of the same age and strain were recruited as the control group. All interventions lasted for 12 weeks by gastrogavage. The fasting blood glucose (FBG), body weight, food intake, water intake, skin temperature, the length of tail, and the degree of fatty liver were monitored. The hemoglobin A1c (HbA1c), total cholesterol (TC), and LDL-C were determined. Endothelin-1 (ET-1) was determined by radioimmunoassay. Nitrogen monoxidum (NO) was determined by nitrate reductase. The kidney tissue VCAM-1 level was analyzed with ELISA. The expression of VCAM-1 mRNA in the kidney tissue was detected with real time quantitative PCR.</p><p><b>RESULTS</b>Compared with the control group, the body weight and food intake decreased, water intake increased in all the other model groups (P < 0.05). Besides, the curve of blood glucose was higher in all the other model groups than in the control group (P < 0.01). Compared with the model group, the body weight increased; levels of HbAlc, TC, LDL-C, ET-1, and VCAM-1 were significantly lower; and skin temperature was higher in the DGR group (P < 0.05, P < 0.01). Compared with the PIO group, body weight, the increment of body weight, FBG, TC, and LDL-C were lower (P < 0.05, P < 0.01); food intake and water intake increased more and the tail length was longer in the DRG group (P < 0.01). There was no statistical difference in the level of NO among groups. The degree of fatty liver in the model group was significantly severer than that in the control group (P < 0.05). It was obviously alleviated in the DGR group (P < 0.05) when compared with the model group and the PIO group (P < 0.05, P < 0.01). But it was severer in the PIO group than in the model group (P < 0.01). The degree of fatty liver in the combination group ranged between that of the DGR group and the PIO group (P < 0.05). The level of VCAM-1 mRNA expression was significantly lower in the DGR group than in the model group, the PIO group, and the combination group (P < 0.05).</p><p><b>CONCLUSIONS</b>DGR had effect in lowering blood glucose and blood lipids, and fighting against fatty liver of transgenic Apo E(-/-) mouse with spontaneous atherosclerosis. DGR played an effective role in preventing and treating DM with angiopathy by comprehensively regulating glycolipid metabolism and promoting the vascular function.</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>

Fetal reduction by bipolar cord coagulation in managing complicated monochorionic multiple pregnancies: preliminary experience in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Monochorionic multiple pregnancies (MMPs) are associated with higher rates of perinatal morbidity and mortality caused by interfetal vascular anastomoses in the monochorionic placenta, which can lead to fetal health interactions. In some circumstances, selective feticide of the affected fetus is necessary to save the healthy co-twin. We evaluated the effects and safety of our initial experiences using bipolar cord coagulation for the management of complicated MMPs.</p><p><b>METHODS</b>Using ultrasound-guided bipolar cord coagulation, we performed selective feticide on 14 complicated MMPs (5 with twin-twin transfusion syndrome, 4 with acardia, 3 with discordant structural anomalies, and 2 with severe selective intrauterine growth restriction). One patient with monochorionic triplets received the procedure twice to terminate 2 affected fetuses for different indications. Data regarding the operations, complications and neonatal outcomes were analyzed.</p><p><b>RESULTS</b>Cord occlusions were successfully performed in 13/14 (93%) cases. The failure happened in an acardiac fetus and the pregnancy was terminated by induction. The included cases delivered at a mean gestational age of 35.4 weeks with a perinatal survival rate of 11/13 (85%). Three operation-related complications occurred (21%), including membrane rupture of the terminated sac (1 case), preterm labor at 28 weeks gestation (1 case), and chorioamniotic membrane separation (1 case). Amnioinfusion was indicated in 11 procedures to expand the target sacs for entering the trocar and obtaining sufficient working space. However, in all 4 cases of acardia, the acardiac sacs showed extreme oligohydramnios and could not be well expanded by infusion; thus, the trocar had to be inserted from the sac of the preserved co-twin.</p><p><b>CONCLUSIONS</b>The application of bipolar cord coagulation in complicated MMPs is safe and improves the prognosis. Amnioinfusion is useful in helping to expand the target sac when the working space is limited.</p>

Prenatal diagnosis of achondroplasia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To diagnose achondroplasia prenatally by FGFR3 gene detection.</p><p><b>METHODS</b>Seventy-eight fetuses affected by short-limb dysplasias were recruited. Umbilical blood sampling was employed to obtain fetal blood for karyotyping and FGFR3 gene detection. Genomic DNA was extracted, and the exon 10 of the FGFR3 gene was amplified. PCR amplicons were analyzed by DNA sequencing and restriction fragment length polymorphism with Bfm I. The FGFR3 exon 10 from the parents of the positive fetuses was screened by the same method.</p><p><b>RESULTS</b>In 78 fetuses affected with short-limb dysplasias, 8 cases had G1138A heterozygotic mutation and normal karyotype, and were diagnosed as achondroplasia. The other 70 fetuses had normal nucleotide at nucleotide 1138 in exon 10 of FGFR3, therefore were excluded from achondroplasia. Only one father in parents of the 8 achondroplasia fetuses also had the G1138A mutation.</p><p><b>CONCLUSION</b>Achondroplasia could be diagnosed prenatally in the fetuses affected with short-limb dysplasias by using PCR-RFLP and DNA sequencing of the exon 10 of the FGFR3 gene.</p>

Relationship between the genotype and hematologic characteristics in the fetuses with thalassemia / 中华儿科杂志

<p><b>OBJECTIVES</b>To investigate the relationship between the genotype and the hematologic characteristics in the fetuses with different types of thalassemia.</p><p><b>METHODS</b>Fetal blood samples were taken by cordocentesis, and hemograms from 572 fetuses at the gestational age of 18 to 38 weeks were examined. According to the genotypes of thalassemia, there were 117 fetuses with heterozygous alpha-thalassemia-1, and 60 with homozygous alpha-thalassemia-1. Twenty had beta-thalassemia mild, and 9 had beta-thalassemia major, respectively. The hematological parameters in these groups were compared with reference group in which 366 cases were included.</p><p><b>RESULTS</b>In alpha-thalassemia groups, hemoglobin (Hb), hematocrit (HCT), mean cell volume (MCV), mean cell hemoglobin (MCH), and mean cell hemoglobin concentration (MCHC) significantly decreased (P < 0.001), but in heterozygous alpha-thalassemia-1, red blood cell (RBC) increased. In homozygous alpha-thalassemia-1, RBC decreased significantly (P < 0.001), but white blood cell and nucleated erythrocyte increased (P < 0.001). There were no significant differences between beta-thalassemia and reference group in most hematological parameters except for decrease of MCHC.</p><p><b>CONCLUSIONS</b>In the fetal period, the hemogram of the fetuses with alpha-thalassemia changes significantly, while it does not change in beta-thalassemia. For the couple with heterozygous alpha-thalassemia, hemogram can provide some information for prenatal screening and diagnosis for those fetuses with alpha-thalassemia, especially for homozygous, but genotype detection is necessary for confirming the diagnosis.</p>