Regulatory effects and mechanisms of branched chain amino acids and metabolic intermediates on insulin resistance / 生理学报

Branched chain amino acids, as essential amino acids, can be used to synthesize nitrogen-containing compounds and also act as signal molecules to regulate substance metabolism. Studies have shown that the elevated level of branched chain amino acids is closely related to insulin resistance and type 2 diabetes. It can affect insulin signal transduction by activating mammalian target of rapamycin (mTOR) signal pathway, and regulate insulin resistance by damaging lipid metabolism and affecting mitochondrial function. In addition, abnormal catabolism of branched amino acids can lead to the accumulation of metabolic intermediates, such as branched chain α-keto acids, 3-hydroxyisobutyrate and β-aminoisobutyric acid. Branched chain α-keto acids and 3-hydroxyisobutyrate can induce insulin resistance by affecting insulin signaling pathway and damaging lipid metabolism. β-aminoisobutyric acid can improve insulin resistance by reducing lipid accumulation and inflammatory reaction and enhancing fatty acid oxidation. This paper systematically reviewed the regulatory effects and mechanisms of branched chain amino acids and their metabolic intermediates on insulin resistance, which will provide a new direction for the prevention and treatment of insulin resistance and type 2 diabetes.

Effect of overexpressed zinc finger protein 580 on apoptosis of oxygen-glucose deprivation SH-SY5Y cells and its possible mechanism / 中华围产医学杂志

Objective:To investigate the expression of zinc finger protein 580 (ZNF580) in oxygen-glucose deprivation (OGD) model of SH-SY5Y cell line and its overexpression on the apoptosis of hypoxic-ischemic neurons and the possible mechanism.Methods:The study was divided into two parts: (1) Human neuroblastoma SH-SY5Y cell line was cultured and divided into the model group and control group. The model group was incubated at 37 ℃ for 6 h in a three-gas incubator of 95% N 2, 5% CO 2, and 0.1% O 2 to establish OGD model, and proteins were extracted at 6, 12, and 24 h after OGD. The expression of ZNF580 was quantified by Western blot. (2) Effects of ZNF580 overexpressed with lentivirus transfection on the apoptosis and cleaved caspase-3 expression: Cells were collected from the control group and model group 24 h after OGD. Overexpressed ZNF580 cells were constructed by lentivirus transfection as the overexpression group and then treated with OGD. Flow cytometry was used to detect the apoptosis rate in the three groups and Western blot was used to detect the expression of cleaved caspase-3. Two independent sample t-test, one-way variance analysis, and LSD- t for pairwise comparison were used for statistical analysis. Results:(1) ZNF580 expression was significantly increased at 6, 12, and 24 h after OGD compared with the control group (1.36±0.05, 2.12±0.07, 1.69±0.05 vs 1.00, LSD- t=9.20, 28.26, and 19.21, all P<0.001). (2) Apoptosis rates of the control, model, and overexpression groups were (1.07±0.56)%, (21.51±1.65)%, and (3.42±0.93)%, respectively, and relative expression levels of cleaved caspase-3 were 1.00, 2.47±0.59, and 1.70±0.25, respectively. Compared with the control group, apoptosis rate and cleaved caspase-3 relative expression level were significantly increased in the model group (LSD- t=21.98 and 8.17, both P=0.001), while the two figures were significantly decreased in the overexpression group when compared with the model group (LSD- t=19.45, P=0.001; LSD- t=4.28, P=0.005). Conclusion:Hypoxia and ischemia could lead to the overexpression of ZNF580, which may reduce the apoptosis of hypoxic-ischemic neurons by inhibiting the expression of cleaved caspase-3 and affecting its enzymatic activation.

Risk factors of postoperative pulmonary infection of gastric cancer and perioperative intervention measures / 中华胃肠外科杂志

Gastric cancer is a common digestive system malignancy. Surgical operation is the main treatment of radical treatment for gastric cancer. Pulmonary infection is a common postoperative complication of gastric cancer. Because there is no clear and unified definition of pulmonary complications, the current researches show that the incidence of postoperative pulmonary infection of gastric cancer is about 1.8%-18.1%. The incidence of postoperative pulmonary infection will prolong the hospital stay, increase the cost of hospitalization, and even develop into respiratory failure leading to early postoperative death. There are many factors affecting postoperative pulmonary infection of gastric cancer, including age, smoking history, pulmonary function, pulmonary disease history, operation method, operation time, intraoperative bleeding volume, gastric tube retention time, postoperative lying time and so on. There are also many perioperative interventions. This article reviews the risk factors and perioperative interventions of postoperative pulmonary infection of gastric cancer.

Survival comparison of Siewert II adenocarcinoma of esophagogastric junction between transthoracic and transabdominal approaches:a joint data analysis of thoracic and gastrointestinal surgery / 中华胃肠外科杂志

OBJECTIVE@#To compare the long-term survival outcomes of Siewert II adenocarcinoma of esophagogastric junction (AEG) between transthoracic (TT) approach and transabdominal (TA) approach.@*METHODS@#The databases of Gastrointestinal Surgery Department and Thoracic Surgery Department in West China Hospital of Sichuan University from 2006 to 2014 were integrated. Patients of Siewert II AEG who underwent resection were retrospectively collected.@*INCLUSION CRITERIA@#(1) adenocarcinoma confirmed by gastroscopy and biopsy; (2) tumor involvement in the esophagogastric junction line; (3) tumor locating from lower 5 cm to upper 5 cm of the esophagogastric junction line, and tumor center locating from upper 1 cm to lower 2 cm of esophagogastric junction line; (4)resection performed at thoracic surgery department or gastrointestinal surgery department; (5) complete follow-up data. Patients at thoracic surgery department received trans-left thoracic, trans-right thoracic, or transabdominothoracic approach; underwent lower esophagus resection plus proximal subtotal gastrectomy; selected two-field or three-field lymph node dissection; underwent digestive tract reconstruction with esophagus-remnant stomach or esophagus-tubular remnant stomach anastomosis above or below aortic arch using hand-sewn or stapler instrument to perform anastomosis. Patients at gastrointestinal surgery department received transabdominal(transhiatal approach), or transabdominothoracic approach; underwent total gastrectomy or proximal subtotal gastrectomy; selected D1, D2 or D2 lymph node dissection; underwent digestive tract reconstruction with esophagus-single tube jejunum or esophagus-jejunal pouch Roux-en-Y anastomosis, or esophagus-remnant stomach or esophagus-tubular remnant stomach anastomosis; completed all the anastomoses with stapler instruments. The follow-up ended in January 2018. The TNM stage system of the 8th edition UICC was used for esophageal cancer staging; survival table method was applied to calculate 3-year overall survival rate and 95% cofidence interval(CI); log-rank test was used to perform survival analysis; Cox regression was applied to analyze risk factors and calculate hazard ratio (HR) and 95%CI.@*RESULTS@#A total of 443 cases of Siewert II AEG were enrolled, including 89 cases in TT group (with 3 cases of transabdominothoracic approach) and 354 cases in TA group. Median follow-up time was 50.0 months (quartiles:26.4-70.2). The baseline data in TT and TA groups were comparable, except the length of esophageal invasion [for length <3 cm, TA group had 354 cases(100%), TT group had 44 cases (49.4%), χ²=199.23,P<0.001]. The number of harvested lymph node in thoracic surgery department and gastrointestinal surgery department were 12.0(quartiles:9.0-17.0) and 24.0(quartiles:18.0-32.5) respectively with significant difference (Z=11.29,P<0.001). The 3-year overall survival rate of TA and TT groups was 69.2%(95%CI:64.1%-73.7%) and 55.8% (95%CI:44.8%-65.4%) respectively, which was not significantly different by log-rank test (P=0.059). However, the stage III subgroup analysis showed that the survival of TA group was better [the 3-year overall survival in TA group and TT group was 78.1%(95%CI:70.5-84.0) and 46.3%(95%CI:31.0-60.3) resepectively(P=0.001)]. Multivariate Cox regression analysis revealed that the TT group had poor survival outcome (HR=2.45,95%CI:1.30-4.64, P=0.006).@*CONCLUSION@#The overall survival outcomes in the TA group are better, especially in stage III patients, which may be associated with the higher metastatic rate of abdominal lymph node and the more complete lymphadenectomy via TA approach.

Moderate-to-vigorous intensity physicaL activity in earLy pregnancy reduces risk of gestationaL diabetes meLLitus / 中华围产医学杂志

Objective To investigate the effects of moderate-to-vigorous intensity physical activity (MVPA) in early pregnancy on the onset of gestational diabetes mellitus (GDM) in Sichuan Province. Methods A case-control study was performed on 1 508 gravidas at 8-14 gestational weeks in Sichuan Provincial Hospital for Women and Children from February to July, 2017. Baseline information during early pregnancy was collected through questionnaires. Information on time and intensity of physical activity were collected through pregnancy physical activity questionnaire. The time spent in MVPA was calculated and was categorized as active ( ≥ 3.5 h/week) or inactive MVPA (<3.5 h/week). Based on self-reported pre-pregnancy weights collected by questionnaire as well as the measured heights, body mass index (BMI) before pregnancy was calculated. After a 75 g oral glucose tolerance test (OGTT) at 24-28 gestational weeks, all subjects were divided into GDM (n=561) or non-GDM group (n=947), according to the GDM diagnostic criteria of the Guidelines for the Diagnosis and Treatment of Pregnancy Diabetes in China (2014). Mann-Whitney U test and Chi-square test were used for statistical analysis. Multivariate unconditional logistic regression model was used to analyze the association between the time of MVPA in early pregnancy and GDM incidence. ResuLts The median time spent in MVPA [M(P25-P75)] in early pregnancy was 3.00 (0.50-3.12) h/week, and 345 gravidas (22.9%) were classified as active in MVPA. After the control of confounding factors such as age, gravidity and parity history, and pre-pregnancy BMI, the multivariate unconditional logistic regression analysis showed that compared with the inactive group, the risk of GDM of active MVPA gravidas was reduced by 26.1% (OR=0.739, 95%CI: 0.553-0.989, P=0.042). Among primigravidas and primiparae, the risk of GDM in active MVPA gravidas was decreased by 47.6% and 44.3% than the inactive ones, respectively (primigravidas: OR=0.524, 95%CI: 0.297-0.925, P=0.026; primiparae: OR=0.557, 95%CI: 0.357-0.868, P=0.010). ConcLusions Insufficient physical activity in early pregnancy is common in gravidas in Sichuan, China. The risk of GDM could be reduced if the frequency of MVPA during early pregnancy is no less than 3.5 h/week, especially in primigravidas and primiparae.

Enterovirus 71 inhibited interferon signaling by downregulating expression of IRF9 / 中国免疫学杂志

Objective:To explore the mechanism of EV71 antagonizing IFN signaling pathway.Methods: RD cells were infected or un-infected with EV71.Then the cells were treated with or without IFN-β.The four groups (the control group,the EV71 group,the IFN-β group,the EV71+IFN-β group) were detected by molecular biology techniques.The expression of interferon stimulated genes (ISGs) were detected by Real-time PCR,while the protein levels of STAT1 and IRF9 were examined by Western blot assay.By preparing the cytosolic and nuclear fractions,the translocation of p-STAT1 was monitored through Western blot assay.Results:Compared with the IFN-β group,the mRNA level of OAS1,MX1 and ISG54 in the EV71+IFN-β group was down regulated by 47%, 50% and 48%,respectively,indicating that EV71 inhibited the expression of ISGs.The results also showed that EV71 did not effect the protein level and phosphorylation of STAT1.Moreover,we found that p-STAT1 was translocated into neuclear in IFN-β group,while p-STAT1 was located in the cytoplasm in the EV71+IFN-β group.And the expression of IRF9 was boviously down regulated in EV71+IFN-β group compared with that in IFN-β group,suggesting that EV71 blocked the expression of IRF9 induced by IFN-β.Conclusion:EV71 inhibited the IFN signaling pathway by downregulating the expression of IRF9 induced by IFN-β.

The expression and modulation of Bax in brain tissue of neonatal rats with hyperbilirubinemia / 中国新生儿科杂志

Objective To study the influence of GM1 on hyperbilirubinemia-induced brain injury in neonatal rats and its possible mechanism.Method A total of 120 7-day-old Sprague-Dawley (SD) rats were randomly assigned into normal control group (n =40),hyperbilirubinemia group (n =40) and GM1 group (n =40).According to the different duration of hyperbilirubinemia,each group was further assigned into 5 subgroups,6 h,12 h,24 h,48 h and 72 h group (n =8).The model of neonatal rat with hyperbilirubinemia was established injecting bilirubin solution (100 μg/g) intraperitoneally.GM1 (10 mg/kg) was injected intraperitoneally immediately after the model was established in GM1 group.Immunohistochemical method was used to determine the expression of Bax in hippocampus.TUNEL method was used to measure the neural cell apoptosis index (AI) in the brain.Result Six hours after the hyperbilirubinemia model was set up,the expression of Bax and AI in hyperbilirubinemia group and GM1 group were examined.The median of AI were 33.5％ and 15.4％ respectively and the average grey value of Bax positive cells were 157.4 ± 2.8 and 162.9 ± 2.3.Both apoptosis cells and the expression of Bax were gradually increasing,and peaked at 72 h after the model was established.The median of AI were 55.5％ and 35.5％ respectively,and the average grey value of Bax positive cells were 127.8 ± 3.6 and 141.5 ±2.7 in hyperbilirubinemia group and GM1 group.And the expressions of Bax and AI in the control group were nearly undetectable.The expression of Bax and AI in GM1 group were lower than hyperbilirubinemia group,but higher than the control group,the differences were statistically significant (P ＜ 0.001).Conclusion Brain cells apoptosis is influenced by hyperbilirubinemia-induced brain injury and Bax may be involved in the process.GM1 may reduce the brain damage by inhibiting the expression of Bax to reduce the apoptosis of the brain cells.

Effect of advanced glycosylation end products on bFGF expression of cultured rabbit Müller cells / 中国免疫学杂志

Objective:To observe the effects of different doses of advanced glycosylation end products ( AGEs ) on bFGF expression of cultured rabbit M üller cells in vitro.Methods:Immunocytochemistry and transmission electron microscopy methods were used identified cultured M üller cell.Immunocytochemistry method was used to semi-quantitate bFGF expression of retinal Müller cells at 640 μl/2 000 μl AGEs conditions.We observed effects of AGEs and PKC inhibitor Calphstion C on bFGF mRNA expression .Results:640 μl/2 000 μl AGEs stimulate bFGF expression of retinal Müller cell.Calphostin C inhibits bFGF mRNA increase stimulated by AGEs,and inhibition achieves strongest at concentration 50 nmol/L.Conclusion:AGEs can stimulate bFGF expression of Müller cell to exert the role of angiogenesis .bFGF mRNA expression may be regulated by activation of PKC pathway .

Injection of submandibular gland with recombinant Exendin-4 and adeno-associated virus for the treatment of diabetic rats / 中南大学学报(医学版)

OBJECTIVE@#To evaluate the therapeutic effects of recombinant Exendin-4 and double-stranded adeno-associated virus (Exendin-4/dsAAV) on SD rats with type 2 diabetes (T2DM) through injecting it into submandibular gland (SG).
@*METHODS@#The Exendin-4/dsAAV was injected into submandibular gland of diabetic rat. The insulin and α-amylase were detected by real-time PCR at the 2nd, 4th and 8th weeks. The immunohistochemisty was used to detect the insulin contents in SG at the 8th week. The concentration of blood glucose and levels of insulin secretion were detected after pancreatectomy.
@*RESULTS@#The SG gland was bigger in Exendin-4/dsAAV group than that in the control group, but the changes in α-amylase were not significant. The Exendin-4 and insulin gene expression was increased in the Exendin-4/dsAAV group (P<0.05). The Exendin-4 and insulin were positive in the SG. The blood glucose was lower and insulin concentration was higher in the Exendin-4/dsAAV group than those in the control group after pancreatectomy (P<0.05), and the insulin content was also increased in the dsAAV groups.
@*CONCLUSION@#Continuous expression of Exendin-4 in SG may improve glucose control and insulin secretion in T2DM rats through inducing expression of insulin.

Perinatal conditions of preterm infants with different severities of respiratory distress syndrome / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To understand the risk factors for respiratory distress syndrome (RDS) by comparing the perinatal conditions of preterm infants with different severities of RDS.</p><p><b>METHODS</b>A total of 667 preterm infants with RDS were classified into 4 groups according to the chest X-ray severity: grade I (217 cases), grade II (225 cases), grade III (126 cases) and grade IV (99 cases). The perinatal conditions of the preterm infants were reviewed retrospectively.</p><p><b>RESULTS</b>There were no significant differences in the gender, the percentage of twins, the percentage of the younger one in twins, maternal age, the percentage of using antenatal corticosteroids, the percentage of premature rupture of membranes, the percentage of placental abruption, the delivery mode and the fertilization mode in preterm infants with different severities of RDS. With the increasing severity of RDS, the birth weight and the gestational age decreased, and the percentage of the infants with Apgar score ≤7 or maternal pregnancy-induced hypertension increased (P<0.05).</p><p><b>CONCLUSIONS</b>The severity of RDS is related to gestational age, birth weight and perinatal asphyxia in preterm infants.</p>