G protein-coupled receptor 35 attenuates nonalcoholic steatohepatitis by reprogramming cholesterol homeostasis in hepatocytes

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Fat accumulation "sensitizes" the liver to insult and leads to nonalcoholic steatohepatitis (NASH). G protein-coupled receptor 35 (GPR35) is involved in metabolic stresses, but its role in NAFLD is unknown. We report that hepatocyte GPR35 mitigates NASH by regulating hepatic cholesterol homeostasis. Specifically, we found that GPR35 overexpression in hepatocytes protected against high-fat/cholesterol/fructose (HFCF) diet-induced steatohepatitis, whereas loss of GPR35 had the opposite effect. Administration of the GPR35 agonist kynurenic acid (Kyna) suppressed HFCF diet-induced steatohepatitis in mice. Kyna/GPR35 induced expression of StAR-related lipid transfer protein 4 (STARD4) through the ERK1/2 signaling pathway, ultimately resulting in hepatic cholesterol esterification and bile acid synthesis (BAS). The overexpression of STARD4 increased the expression of the BAS rate-limiting enzymes cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and CYP8B1, promoting the conversion of cholesterol to bile acid. The protective effect induced by GPR35 overexpression in hepatocytes disappeared in hepatocyte STARD4-knockdown mice. STARD4 overexpression in hepatocytes reversed the aggravation of HFCF diet-induced steatohepatitis caused by the loss of GPR35 expression in hepatocytes in mice. Our findings indicate that the GPR35-STARD4 axis is a promising therapeutic target for NAFLD.

Hospitalization time and family financial burden of children under 14 years old with severe asthma / 公共卫生与预防医学

Objective To explore the hospitalization time and family financial burden of children under 14 years old with severe asthma in this region. Methods Children under 14 years old with severe asthma who were admitted to our hospital from January 2017 to December 2019 as a result of an acute attack were selected in this study. Questionnaire surveys, hospital charging system, and follow-up methods were used to collect clinical data, length of hospital stay, and direct and indirect costs of the children with asthma. Stepwise regression was applied to analyze the factors influencing the total cost. Results A total of 206 children were enrolled from 2017 to 2019, including 117 males and 89 females, with an average age of (7.24±1.53) years old. The total age distribution mainly consisted of six months to 3 years old (33.01%), >3 to 4 years old (24.27%), and >6-13 years old (20.39%). The onset season was mainly autumn and winter (33.01%). The average length of hospital stay was (8.50±1.42) d. The annual average family cost was (6884.20±957.61) RMB. The length of hospital stay decreased year by year, while the total cost increased year by year (P<0.05). Multiple stepwise regression analysis showed that the length of hospitalization, antibiotic use time, and presence/absence of allergic rhinitis, pulmonary heart disease and GINA standard treatment were the related factors affecting the total cost in children with severe asthma (P<0.05). Conclusion From 2017 to 2019, the hospitalization time of children under 14 years old with severe asthma in this region decreased over time, while the total cost gradually increased. Shortening the hospitalization time, actively preventing and controlling complications, and standardizing treatment can effectively reduce the financial burden of children's families.

Hypoxic condition monitoring and treatment evaluation for non-small cell lung cancer before and after radiotherapy by 18F-FMISO PET/CT / 中华核医学与分子影像杂志

Objective To evaluate the changes of hypoxic conditions in non-small cell lung cancer (NSCLC) patients before and after radiotherapy and assess the value of 18F-fluoromisonidzaole (FMISO)PET/CT for radiotherapy efficacy evaluation.Methods A total of 21 NSCLC patients (15 males,6 females,age 30-74 years) from January 2014 to October 2016 were prospectively enrolled.18F-FMISO PET/CT was performed before and after radiotherapy,and all patients underwent 18F-fluorodeoxyglucose (FDG)PET/CT before radiotherapy.Routine chest CT was performed at the 3rd and 6th month after radiotherapy.The maximum standardized uptake value (SUVmax) of tumor and muscle,tumor volume and hypoxic volume (HV) were measured.Tumor-to-muscle (T/M) value of 18F-FMISO was calculated,and T/M ≥ 1.3 was considered as the hypoxia cut-off value.Data were analyzed using Pearson correlation,paired t test,signed rank sum test and Wilcoxon rank sum test.Results Totally 81.0％(17/21) of NSCLC patients had hypoxia.There were significant positive correlations between 18F-FMISO T/M value and tumor volume or 18F-FDG SUVmax(r:0.72,0.60,both P＜0.05).The T/M value after radiotherapy was significantly lower than that before radiotherapy (1.42± 1.12 vs 2.08±0.71;t =3.62,P＜0.05),and median HV was also significantly lower than that before radiotherapy (6.53 vs 12.41 cm3;z =-3.83,P＜0.05).The median T/M values of effective group (n =14) and ineffective group (n =7) before radiotherapy were significantly different (2.14 vs 2.87;z=-2.27,P＜0.05),and the median HV of 2 groups before radiotherapy was also significantly different (6.43 vs 10.20 cm3;z=-2.14,P＜0.05).Conclusions Most NSCLC patients have hypoxia before radiotherapy.The larger tumor volume,the higher degree of hypoxia.Radiotherapy can alleviate the hypoxia of tumors.18F-FMISO PET/CT imaging before radiotherapy can be used to predict the efficacy of patients with NSCLC.

The role of apolipoprotein C4 in vascular endothelial cell injury in hypertensive disorder of pregnancy / 中华检验医学杂志

Objective Find abnormal changes of plasma lipid metabolism-related proteins before 20 weeks of gestation in patients with hypertensive disorder of pregnancy(HDP), and preliminarily investigate the role of plasma apolipoprotein C4 elevation in HDP. Methods A nested case-control study was used. The plasma were collected from pregnant women who underwent routine prenatal examination in Guangzhou Women and Children's Medical Center from November 2014 to March 2017. Label-free mass spectrometry was used to detect the differences in plasma lipid metabolism-related proteins before 20 weeks of gestation between 12 pairs of HDP patients and normal controls, and different 48 pairs of samples were used for verification. The protein with the most significant difference multiples was screened to study its effects on monolayer permeability and nitric oxide secretion of endothelial cells. One-way ANOVA was used for comparison between groups, and P<0.05 was considered as statistically significant difference. Results Compared with the control, the lipid metabolism-related proteins, APOC4, Fatty acid-binding protein 4 (FABP4), Apolipoprotein E (APOE), Apolipoprotein C3 (APOC3) and Beta-2-glycoprotein 1(APOH) raised to 1.94, 1.82, 1.59, 1.55 and 1.38 times, phospholipid transfer protein (PLTP) decreased to 0.78 times in plasma before 20 weeks of pregnancy of patients with HDP (t value were 2.499, 2.497, 2.081, 2.098, 2.426 and 2.564, respectively, P<0.05). Cell experiments results showed that 50 ng / ml APOC4 significantly increased 20％ HUVEC single layer cell permeability to FITC-labeled dextran (F=455.4, P<0.01), and significantly decreased the level of nitric oxide in the supernatant of HUVEC culture by 25％ (F=61.92, P<0.01). Conclusions Before diagnosis, plasma protein levels involved in lipid metabolism in HDP patients have been changed, resulting in abnormal lipid metabolism. APOC4 can increase the permeability of vascular endothelial cells, inhibit endothelial source of NO secretion, cause endothelial dysfunction.

Medical health integration continuance management mode in the prevention of elderly patients after dis-charge in bed household application effect analysis of pressure ulcers / 中华护理杂志

Objective Discuss medical health integration continuance management mode in the prevention of elderly patients after discharge in bed household application effect of pressure ulcers. Methods To 120 cases of elderly patients in bed in hospital time order is divided into control group and experimental group,by the medical health outreach group respectively in the hospital two days before the assessment of patients and family rehabilitation plan,the control group given conventional discharge and telephone follow-up after discharge,the experimental group according to the medical health integration management mode,made up of medical health outreach team to stay in bed for elderly patients after discharge pressure ulcer risk factors assessment,targeted prevention of pressure sores rehabilitation plan,group management,remote care joint family supervision,timely follow up the capa and the exami-nation of the effect,the pressure ulcer management and quality of life scale to compare two groups of patients at discharge,6 months after hospital discharge,the quality of life of 12 months after discharge and the incidence of pressure ulcers in a year. Results The experimental group was lower than those of control group,the incidence of pressure ulcers was statistically significant difference(P0.05). Conclusion Medical health integration continuance management can effectively reduce the incidence of pressure ulcers that occupy the home stay in bed for elderly patients,improve their quality of life.

Clinical application value of serum amyloid A protein and C reactive protein in early diagnosis of hand-foot-mouth disease in children / 国际检验医学杂志

Objective To explore the clinical application value of serum amyloid protein(SAA) and C reactive protein(CRP)in early diagnosis of hand‐foot‐mouth disease(HFMD)in children .Methods The serum/plasma levels of CRP and SAA in 81 children with HFMD(HFMD group)and 125 healthy children(healthy control group)were detected by using dot immunogold filtration as‐say .Data including white blood cell (WBC) count ,levels of CRP and SAA were obtained and analyzed .And diagnostic efficacies of these indicators were evaluated by using receiver operating characteristic (ROC) curve .Results The serum levels of SAA and CRP and WBC count in HFMD group were significantly higher than those in healthy control group ,and all had statistically significant differences(P<0 .05) .The area under the ROC curve(AUC) of SAA(0 .921) was higher than that of CRP(0 .728) ,SAA/CRP ra‐tio(0 .846) and WBC count(0 .721) for diagnosing HFMD ,there were statistically significant differences(P<0 .05) .Compared with CRP ,WBC count and SAA/CRP ratio ,SAA had better diagnostic efficacy .Conclusion As a new biomarker of infections ,SAA can effectively diagnose HFMD early and provide more sensitive reference to clinicians for early diagnosis ,which might be worthy of clinical application widely .

Effect of thyroid hormones on the expression of thyroid hormone receptor isoforms in human osteogenic sarcoma cell line MG-63 / 中华内分泌代谢杂志

Objective To examine the expression of thyroid hormone receptor isoforms (TR α1, α2, β1, and β2) in human osteoblast-like cell line MG-63 at the mRNA level and the effect of thyroid hormone (T3 or T4 ) on the expression. Methods Realtime quantitative PCR was performed. Results The expression of TRα1 mRNA was the highest, that was 10. 70± 0.45, TRβ1 was 5.75 ± 0. 10, TRβ2 was 3.34 ± 0. 08, and TRα2 was very low, only (3.66 ±0. 59) × 10-2. Only the expression of TRαl and TRα2 mRNA was down regulated significantly by the treatment of 10-10 ～ 10-6 mol/L T3, and there was a negative correlation between the expression of TRα1 or TRα2 mRNA and the concentration of T3. Conclusion TRα1 plays a primary role in mediating the effects of thyroid hormones in skeletal development.

The thyroid hornone receptor in human osteogenic sarcoma cell line MG-63 cell-T3 binding studies with nuclear extracts / 中华内分泌代谢杂志

To establish a method for radioligand binding assay of thyroid hormone receptors(TR)in human osteoblast-like osteosarcoma cell line MG-63 and to estimate the kinetic parameters of putative receptors. The MG-63cell was cultured in Ham's F12, the soluble TR was prepared from the intact nuclear extracts. The binding properties between TR and T3 were performed by using the traditional Scatchard analysis. The apparent Ka of TR in MG-63 is 7.68× 109 L/mol, and MBC(111. 25+ 10.77)fmol/mg protein. The study indicated that MG-63 cells possessed high affinity and limited-capacity of TR in its nuclear extracts. This may serve as the starting and basic work about TR in bone cell.

Comparison of Immune Responses Elicited by Recombinant Fusion Hapten and Coupled Hapten / 天津医药

Objective:To identify the immune characteristics elicited by immunogen prepared in two different ways against a 36AA-peptide. Methods：Rabbits were immunized by a 36-AA-hapten coupled with carrier proteins or recombinant fusion protein separately. The kinetics and specificities of antibody responses were compared. Results：After about 3 months of primary immunity, the antisera elicited by two kinds of immunogen reached the peak titer. The highest titer elicited by the immunogen prepared with coupled-hapten method reached 1∶12 000, while the highest titer elicited by the immunogen prepared with gene engineering method was 1∶6 000. But the immune response produced by the recombinant fusion protein was more long-lasting. Conclusion：Both kinds of immunogen can successfully elicit 36-AA specific antibody response in rabbits, which have different immune characteristics. To couple the hapten with vector proteins is a quicker and more effective way to prepare the immunogen.

ASSAY OF TYPE I IODOTHYRONINE DEIODINASE ACTIVITY AND mRNA EXPRESSION IN THYROID IN RATS OF DIFFERENT IODINE NUTRITION STATUS / 营养学报

Objective: To further investigate the effects of iodine intake on thyroid function and its possible mechanism. Method: Wistar rats were randomly divided into six groups: LI, NI, 5HI, 10HI, 50HI, 100HI. Different groups of rats were fed with feed and water of different iodine content. 3, 6 and 12 months after administration, they were sacrificed and thyroids were excised. The thyroid D1 mRNA expression level was determined by RT-PCR semi-quantitative method and the thyroid D1 activity was analyzed by using 125I-rT3 as substrate. Results: Compared with NI group, the thyroid D1 mRNA expression was decreased in all HI groups, and D1 activity was significantly higher in LI group and lower in HI groups. There was a tendency of decrease in D1 activity with increased doses of iodine intakes. Conclusion: In the case of iodine deficiency, thyroid D1 activity will increase greatly in order to convert more T4 to T3, but deficient iodine intake doesn’t improve thyroid D1 mRNA expression. Excess iodine can inhibit both thyroid D1 mRNA expression and its activity.