Objective To study the effect and mechanism of endoplasmic reticulum stress on hippocampal neuron apoptosis and cognitive impairment in type 1 diabetic rats. Methods Ten rats were randomly selected as normal control group (Con group) from thirty Wistar rats, and the remaining twenty rats were intraperitoneally injected with streptozotocin to prepared for type 1 diabetic rat model. The successful model rats were randomly divided into diabetic group (DM group) and diabetic +Salubrinal group (DM+Sal group). Rats of DM+Sal group were injected by lateral ventricle with Salubrinal ( 75μmol/L, 1μL). Rats of Con group and DM group were given the equal volume of normal saline. The rat cognitive function was assayed by Morris water maze test. The hippocampal neuron apoptosis was detected by TUNEL and flow cytometry methods. The protein levels of endoplasmic reticulum stress markers, GRP78, CHOP and Caspase12, and the mRNA levels of GRP78 and CHOP, were examined by Western blot assay and Real-time PCR, respectively. Results Compared with the Con group, the cognitive function was significantly decreased in DM group, and the apoptotic rate of hippocampal neurons was increased. The protein levels of endoplasmic reticulum stress markers GRP78, CHOP and Caspase12 were significantly increased (P<0.05), and the mRNA levels of GRP78 and CHOP were also higher in DM group (P<0.05). After the injection with Salubrinal, the cognitive function was improved and hippocampal neuron apoptotic rate was decreased in DM+Sal group compared with those of DM group. Moreover, the protein levels of GRP78, CHOP and Caspase12 were significantly decreased (P<0.05) and the mRNA levels of GRP78 and CHOP were also lowered in DM+Sal group (P<0.05). Conclusion The cognitive impairment and the higher apoptotic rate appear in the diabetic rats, and endoplasmic reticulum stress may play an important role in it.

Objective:To study the relationship between rs 2228314 polymorphism in sterol regulatory element binding protein 2 gene (SREBP2) and obesity, serum lipid levels in children and adolescents . Methods:In our study , 2 030 children and adolescents aged from 7 to 18 years participated .Anthropo-metric measurements, including height and weight, were performed.Their serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol ( HDL-C) were detected .The matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS ) was used to detect rs2228314 genotypes.Results: The GC/CC genotypes of rs2228314 polymorphisms had lower HDL-C levels than GG genotype [(0.10 ±0.35) mmol/L vs. (0.14 ±0.36) mmol/L, P=0.020].The rs2228314 polymorphism was associated with the abnormal HDL-C level under the dominant model after adjustment for study samples , sex and age ( OR=1.400, 95%CI:1.027-1.907, P=0.033).The rs2228314 polymorphism was not associated with obesity un-der the dominant model after adjustment for study samples , sex, age and HDL-C level ( OR=1.178, 95%CI: 0 .971 -1 .430 , P =0 .096 ) . Conclusion: The GC/CC genotype carriers of SREBP2 rs2228314 polymorphism have higher risk of abnormal HDL-C level than the individuals with GG geno-type among children and adolescents .

Objective: To examine the association between polymorphism of rs10185316 in insulin-induced gene 2 (INSIG2) and blood pressure among children and adolescents. Methods: 9 junior middle schools in Dongcheng District of Beijing and 5 schools (3 primary junior middle schools, 2 primary schools) in Haidian District of Beijing were chosen in 2005 and 2007, respectively. According to the Chinese BMI percentile criteria for screening overweight and obesity in school children, we recruited 1 425 overweight or obese children and 605 normal weight children. A total of 2 018 students with complete data of blood pressure and genotype data were included in this study. According to the blood pressure criterion of children and adolescents, 702 participants were categorized into high blood pressure group and 1 316 into normal blood pressure group. Participants' information of gender, age, height, weight and blood pressure were collected by questionnaire and physical examination. Genomic DNA was extracted from peripheral blood sample for genotyping of INSIG2 rs10185316 polymorphism. Multiple linear regression was conducted to analyze the associations between rs10185316 polymorphism in INSIG2 and SBP, DBP, mean arterial pressure (MAP) and pulse pressure. Results: The age, BMI, SBP and DBP of the high blood pressure group were separately (14.3±1.4) years old, (27.3±4.2) kg/m², (130.5±10.9) and (76.7±13.3) mmHg (1 mmHg=0.133 kPa), all higher than that of the normal blood pressure group, which were (12.2±2.9) years old, (22.0±4.0) kg/m², (104.4±10.9) and(54.6±15.2) mmHg, respectively (all P values<0.001). After age, sex, district and BMI adjusted, compared with the participants carrying INSIG2 rs10185316 CC genotype, CG/GG genotype carriers had lower DBP (β(95%CI):-1.67(-2.84--0.50), P=0.005), higher PP(β(95%CI): 1.91(0.61-3.20), P=0.004), and lower MAP(β(95%CI):=-1.03(-2.01--0.05), P=0.039). Conclusion INSIG2 rs10185316 polymorphism was associated with DBP, PP and MAP among children and adolescents in an independent way from BMI.

Objective:To observe the glycemic profiles and emotion management in diabetic patients after the outbreak of novel coronavirus disease 2019(COVID-19).Methods:A questionnaire survey was used to observe the blood glucose levels and metabolic indexes before and after the outbreak of COVID-19, and to detect emotion ratings after the outbreak of COVID-19. The aim of the study is to present the effects of the COVID-19 on glycemic and emotional management in diabetic patients.Results:A total of 136 patients were included in this survey. The average age of the patients was 62.5 years old, and the average duration of diabetes was 10.1 years. Glycemic profiles(fasting blood glucose, 2 h postprandial blood glucose, HbA 1C), lipid profiles(triglycerides, low-density lipoprotein cholesterol), and body weight were not significantly different before and after the outbreak of COVID-19( P>0.05). According to emotional scales(scores of anxiety, depression, and sleep-related scales), 76.5% diabetic patients did not develop anxiety symptoms, 61.0%~69.9% diabetic patients did not have depressive symptoms and 52.0% diabetic patients did not have sleep disorder. 19.9% diabetic patients had mild anxiety symptoms, 25.7%~30.9% diabetic patients presented mild depression symptoms and 28.3% diabetic patients had mild sleep disorders. 2.9% diabetic patients had moderate anxiety, 2.2%~8.1% diabetic patients had moderate depression and 14.2% diabetic patients had moderate sleep disorder. Only a very small part of patients presented severe emotional symptoms including 0.7% patients with anxiety symptoms(GAD-7 15 points and above), 2.2% patients with depressive symptoms(PHQ9 and PHQ15 15 points and above)and 5.6% patients with sleep symptoms(PSQI 15 points and above). Compared with asymptomatic patients, neither patients with mild and moderate/severe depression and sleep disorder showed significant difference in HbA 1C, nor did patients with moderate/ severe anxiety symptoms. However, patients with mild anxiety symptoms showed significant lower HbA 1C than asymptomatic patients. Conclusion:After the outbreak of COVID-19, there was an increasing trend in blood glucose, but there was no statistical difference. Body weight, lipids profiles were not different in diabetic patients, either. Most of diabetic patients had mild symptoms of anxiety, depression and sleep disorders. Very few patients presented moderate to severe symptoms of anxiety, depression and sleep disorders.

Objective To investigate the association between rs780094 polymorphism in glucokinase regulatory protein (GCKR) and plasma lipid levels in children and adolescents. Methods 1 026 Chinese children aged 7 to 18 years were recruited,with anthropometric measurements,detection of plasma lipid levels and genotyping of rs780094 performed. Relationships between polymorphism and plasma lipid levels were tested,using multivariate linear regression and logistic regression. Results A-allele of rs780094 in GCKR was associated with increased TC,TG and LDL-C levels(b=0.06 mmol/L,P=0.037;b=0.09 mmol/L,P<0.001;b=0.05 mmol/L,P=0.040) under the additive model adjusted for age,age square and gender. The rs780094 in GCKR was also associated with abnormal levels of TG and LDL-C(OR=1.60,95%CI:1.30-1.97,P<0.001;OR=1.35,95%CI:1.02-1.80,P=0.036). Conclusion The rs780094 in GCKR was associated with plasma lipid levels in children and adolescents while A-allele of rs780094 might serve as genetic factor for the increased plasma lipid levels.

Alzheimer's disease (AD) is the most common form of dementia in the elderly, and there is no specific treatment to stop or reverse its progression. Mild cognitive impairment (MCI) is an important entry point for early diagnosis and prevention of AD. More and more studies have explored the risk factors and biomarkers for conversion from MCI to AD, and a series of risk prediction models have been established. This article analyzes and summarizes the different predictors and risk prediction models so as to provide basis for early identifying the high-risk group of AD, managing the controllable risk factors, and providing references for the selection and improvement of these models.

OBJECTIVETo investigate the association between rs780094 polymorphism in glucokinase regulatory protein (GCKR) and plasma lipid levels in children and adolescents.

METHODS1 026 Chinese children aged 7 to 18 years were recruited, with anthropometric measurements, detection of plasma lipid levels and genotyping of rs780094 performed. Relationships between polymorphism and plasma lipid levels were tested, using multivariate linear regression and logistic regression.

RESULTSA-allele of rs780094 in GCKR was associated with increased TC, TG and LDL-C levels (b = 0.06 mmol/L, P = 0.037; b = 0.09 mmol/L, P < 0.001; b = 0.05 mmol/L, P = 0.040) under the additive model adjusted for age, age square and gender. The rs780094 in GCKR was also associated with abnormal levels of TG and LDL-C(OR = 1.60, 95% CI:1.30-1.97, P < 0.001;OR = 1.35, 95%CI:1.02-1.80, P = 0.036).

CONCLUSIONThe rs780094 in GCKR was associated with plasma lipid levels in children and adolescents while A-allele of rs780094 might serve as genetic factor for the increased plasma lipid levels.

Adolescent ; Carrier Proteins ; genetics ; Child ; Female ; Genotype ; Humans ; Lipids ; blood ; Logistic Models ; Male ; Polymorphism, Genetic

OBJECTIVE: Hepatic fibrosis has been widely considered as a conjoint consequence of almost all chronic liver diseases. Chuanxiong Rhizoma (Chuanxiong in Chinese, CX) is a traditional Chinese herbal product to prevent cerebrovascular, gynecologic and hepatic diseases. Our previous study found that CX extracts significantly reduced collagen contraction force of hepatic stellate cells (HSCs). Here, this study aimed to compare the protection of different CX extracts on bile duct ligation (BDL)-induced liver fibrosis and investigate plausible underlying mechanisms. METHODS: The active compounds of CX extracts were identified by high performance liquid chromatography (HPLC). Network pharmacology was used to determine potential targets of CX against hepatic fibrosis. Bile duct hyperplasia and liver fibrosis were evaluated by serologic testing and histopathological evaluation. The expression of targets of interest was determined by quantitative real-time PCR (qPCR) and Western blot. RESULTS: Different CX extracts were identified by tetramethylpyrazine, ferulic acid and senkyunolide A. Based on the network pharmacological analysis, 42 overlap targets were obtained via merging the candidates targets of CX and liver fibrosis. Different aqueous, alkaloid and phthalide extracts of CX (CX_AE, CX_AL and CX_PHL) significantly inhibited diffuse severe bile duct hyperplasia and thus suppressed hepatic fibrosis by decreasing CCCTC binding factor (CTCF)-c-MYC-long non-coding RNA H19 (H19) pathway in the BDL-induced mouse model. Meanwhile, CX extracts, especially CX_AL and CX_PHL also suppressed CTCF-c-MYC-H19 pathway and inhibited ductular reaction in cholangiocytes stimulated with taurocholate acid (TCA), lithocholic acid (LCA) and transforming growth factor beta (TGF-β), as illustrated by decreased bile duct proliferation markers. CONCLUSION Our data supported that different CX extracts, especially CX_AL and CX_PHL significantly alleviated hepatic fibrosis and bile duct hyperplasia via inhibiting CTCF-c-MYC-H19 pathway, providing novel insights into the anti-fibrotic mechanism of CX.

Liver fibrosis is a dynamic wound-healing response characterized by the agglutination of the extracellular matrix (ECM). Si-Wu-Tang (SWT), a traditional Chinese medicine (TCM) formula, is known for treating gynecological diseases and liver fibrosis. Our previous studies demonstrated that long non-coding RNA H19 (H19) was markedly upregulated in fibrotic livers while its deficiency markedly reversed fibrogenesis. However, the mechanisms by which SWT influences H19 remain unclear. Thus, we established a bile duct ligation (BDL)-induced liver fibrosis model to evaluate the hepatoprotective effects of SWT on various cells in the liver. Our results showed that SWT markedly improved ECM deposition and bile duct reactions in the liver. Notably, SWT relieved liver fibrosis by regulating the transcription of genes involved in the cytoskeleton remodeling, primarily in hepatic stellate cells (HSCs), and influencing cytoskeleton-related angiogenesis and hepatocellular injury. This modulation collectively led to reduced ECM deposition. Through extensive bioinformatics analyses, we determined that H19 acted as a miRNA sponge and mainly inhibited miR-200, miR-211, and let7b, thereby regulating the above cellular regulatory pathways. Meanwhile, SWT reversed H19-related miRNAs and signaling pathways, diminishing ECM deposition and liver fibrosis. However, these protective effects of SWT were diminished with the overexpression of H19 in vivo. In conclusion, our study elucidates the underlying mechanisms of SWT from the perspective of H19-related signal networks and proposes a potential SWT-based therapeutic strategy for the treatment of liver fibrosis.
Humans ; RNA, Long Noncoding/genetics* ; Liver Cirrhosis/genetics* ; Liver/metabolism* ; Hepatic Stellate Cells/pathology* ; MicroRNAs/metabolism* ; Extracellular Matrix/metabolism* ; Drugs, Chinese Herbal