group pACT-apoA Ⅰ and pBIND-core was higher than that in the negative control.Conclusion HCV core protein and apoA Ⅰ can interact in vivo.This study provides new theory for the mechanism of chronicity hepatitis C in fatty liver.

A new type of fluorescent gold nanoclusters (MU-Au NCs) was prepared by hydrothermal synthesis method using ammonium benzoate murexide (MU) as reducing agent and protecting agent.The synthesis method was simple and rapid.Based on the fluorescence quenching ability of spermine, a turn off type fluorescence analysis method was established for rapid and ultra sensitive detection of spermine.The linear range for detection of spermine was 0.003-300 μmol/L and the detection limit was 1 nmol/L (S/N=3).The established analytical method of spermine provided theoretical basis and reference for construction of spermine biosensor and actual sample detection.

OBJECTIVETo obtain geranylgeranyl diphosphate synthase gene of Salvia miltiorrhiza, and conduct bioinformatic and transcript expression analysis of the cloned SmGGPS1 gene.

METHODThe degenerate primers were designed based on the conservative regions of GGPS protein sequences from public databases. The target gene was obtained from root of S. miltiorrhiza by use of homologous cDNA amplification and RACE technologies. The sequence alignment was performed using BLAST. The open reading frame was identified by use of the ORF Finder. The protein domains were defined by use of Prosite software and the signal peptide sequence was predicted by Target P1.1. MEGA4.0 was used to conduct multiple amino acid sequence alignment and construct the phylogenetic tree. Roots and leaves at the seedlings stage and roots, stems, leaves, buds and flowers in the flowering stage were sampled for transcript analysis. Semi-quantitative RT-PCR was used to detect the gene expression level. The complete gene of GGPS was obtained from S. miltiorrhiza genomic DNA by PCR using the cDNA-derived specific primer. The gene structure of GGPS was analyzed by comparison of the genomic DNA and its cDNA.

RESULTThe obtained 1 298 bp SmGGPS1 cDNA sequence contains an 1095 bp ORF, encoding 364 amino acids. It is predicted that it has a plastid targeting signal peptide of approximately 52 amino acid at the N-terminal end. It is to believe that this is the polyprenyl synthetase signature, and nucleic acid sequence comparison revealed that SmGGPS1 ORF has more than 60% identity to the reported GGPS. RT-PCR semi-quantitative analysis showed that the gene expresses in the all tested tissues, and with much higher level of expression in the leaves in the flowering stage. SmGGPS1 has a 397 bp intron.

CONCLUSIONFor the first time the cloning of geranylgeranyl diphosphate synthase gene from S. miltiorrhiza was reported, and it provides a good basis for further functional study of SmGGPS1.

Amino Acid Sequence ; Base Sequence ; Cloning, Molecular ; Farnesyltranstransferase ; chemistry ; genetics ; metabolism ; Gene Expression Regulation, Enzymologic ; Molecular Sequence Data ; Open Reading Frames ; Phylogeny ; Plant Proteins ; genetics ; metabolism ; Plants ; classification ; enzymology ; genetics ; Salvia miltiorrhiza ; classification ; enzymology ; genetics

Objective: To explore the influencing factors affecting the cognitive impairment of the elderly population in China. Methods: A stratified multi-stage cluster sampling was used in 6 provinces (autonomous administrative regions and municipalities) to select the sample. A total 24 000 urban and rural residents aged 60 years and above received a set of standardized questionnaire interview, physical examinations, laboratory test of lipid and glucose levels of blood and apolipoprotein E (APOE) genotype. The primary screening of cognitive function was assessed by using the Chinese Version of Ascertain Dementia 8, and then suspicious cognitive impairment cases with more than two abnormal results would receive the further cognitive function assessment by using the Mini-Mental State Examination (MMSE). 1 300 cases with cognitive impairment and 2 600 controls without cognitive impairment were recruited and matched according to their age, gender and resident area in a 1∶2 case-control study. The conditional logistic regression model was used to analyze the association between relevant factors and cognitive impairment. Results: Factors negatively associated with cognitive impairment and their OR (95%CI) values were primary or middle school as 0.63 (0.51-0.77), high school and above as 0.59 (0.39-0.88), daily neighborhood communication as 0.61 (0.50-0.75), weekly participating in social activities 0.59 (0.44-0.79), daily tea drinking as 0.71 (0.58-0.88) and doing regular exercise as 0.71 (0.57-0.88), reading newspaper (occasional: 0.50 (0.37-0.67); frequent: 0.40 (0.28-0.57)), playing majiang or cards (occasional: 0.51 (0.34-0.74); frequent: 0.50 (0.36-0.68)) respectively. Factors positively associated with cognitive impairment and their OR (95%CI) values were APOE-ε4 heterozygote as 1.31 (1.08-1.58), homozygote as 2.74 (1.52-5.00), diabetes onset before 50 years of age and after as 9.03 (3.07-33.60) and 4.40 (3.18-6.17), stroke as 1.90 (1.35-2.69), asthma as 1.95 (1.11-3.42) respectively. Conclusion APOE-ε4 alleles, lower educational level, stroke, asthma, diabetes are risk factors of cognitive impairment in the elderly. Keeping a healthy lifestyle and preventing chronic diseases in the whole life course could significantly reduce the incidence of cognitive impairment in the elderly.

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a patient with adolescent-onset hypomyelinated leukodystrophy with atrophy of basal ganglia and cerebellum (H-ABC). METHODS: A patient who was diagnosed with H-ABC in March 2018 at the First Affiliated Hospital of Nanjing Medical University was selected as the study subject. Clinical data was collected. Peripheral venous blood samples of the patient and his parents were collected. The patient was subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. RESULTS: The patient, a 31-year-old male, had manifested with developmental retardation, cognitive decline and abnormal gait. WES revealed that he has harbored a heterozygous c.286G>A variant of the TUBB4A gene. Sanger sequencing confirmed that neither of his parents has carried the same variant. Analysis with SIFT online software indicated the amino acid encoded by this variant is highly conserved among various species. This variant has been recorded by the Human Gene Mutation Database (HGMD) with a low population frequency. The 3D structure constructed by PyMOL software showed that the variant has a harmful effect on the structure and function of the protein. According to the guidelines formulated by the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic. CONCLUSION The c.286G>A (p.Gly96Arg) variant of the TUBB4A gene probably underlay the hypomyelinating leukodystrophy with atrophy of basal ganglia and cerebellum in this patient. Above finding has enriched the spectrum of TUBB4A gene variants and enabled early definitive diagnosis of this disorder.
Male ; Humans ; Adolescent ; Adult ; Magnetic Resonance Imaging ; Basal Ganglia/pathology* ; Cerebellum ; Atrophy/pathology* ; Mutation ; Tubulin/genetics*

Objective:Investigating the distribution of intestinal Akkermansia muciniphila (AKK) and explore abundance-effect in obesity obesity to provide potential dose effect for obesity intervention.Methods:Clinical data of 6 986 subjects including body mass index, waist circumference, and common confounders such as gender, age, diastolic blood pressure, systolic blood pressure, fasting blood glucose, triglyceride, total cholesterol, high density lipoprotein-cholesterol, low density lipoprotein-cholesterol, and uric acid were collected from Guangdong Gut Microbiome Project in 2008. 16S ribosomal RNA (16S rRNA) sequencing data were used to estimate the genus abundance of AKK as well as its operational taxonomic unites (OTUs). Central obesity and overall obesity were diagnosed according to the criteria of China Obesity Working Group in 2002. Multivariate logistic regression was used to analyze the OR (95% CI) of obesity with one-unite elevation of AKK. The dose effect of AKK on obesity was estimated by comparing the trend of ORs from the 1st to the 20th quantile. Results:A total of three AKK OTUs(AKK OTU1, AKK OTU2, AKK OTU3) were identified: AKK OTU1 and AKK OTU2 were distributed in more than 90% of the population, while AKK OTU3 was distributed at 21.7%; All the OTUs showed a"bimodal"distributional pattern and their correlations with common factors were variable. Disparities of the association with obesity were found between the OTUs and the AKK. AKK OTU1, AKK OTU2, and the genus level of AKK showed significant protective effects against obesity; The ORs (95% CI) were 0.95(0.93-0.98), 0.97(0.94-0.99), 0.93(0.91-0.96), respectively for central obesity; And ORs(95% CI) were 0.88(0.80-0.97), 0.98(0.93-1.02), 0.81(0.74-0.89), respectively for overall obesity. The results were similar after adjustment for common confounders. According to the calculation of dose-effect, the protect effects of AKK increased with accumulated abundance and the minimum effective dose on central obesity and overall obesity was 1.83% and 4.98%, respectively. Conclusion:AKK is a protective factor for obesity, but the dose-effect of AKK and the strain-differences should be considered in the future interventional study.

Objective:To analyze the relationship between physical indicators and blood pressure or fasting plasma glucose levels in the young-old and oldest-old.Methods:Totally 1 516 subjects from the Guangxi Natural Longevity Cohort were screened in this study and physical examination parameters included body mass index(BMI), waist circumference(WC), waist-to-height ratio(WHtR), fasting plasma glucose(FPG)and blood pressure, and the correlations between them were analyzed.Results:The overweight elderly and overweight young elderly groups had an increased risk of concurrent hypertension and impaired fasting glucose, compared with both elderly people with normal BMI and young elderly people with normal BMI( OR=2.66, 95% CI: 1.90-3.72; OR=3.03, 95% CI: 2.11-4.34). Elderly people with general obesity and young elderly people with general obesity were more likely to have hypertension( OR=5.25, 95% CI: 2.07-13.28; OR=4.75, 95% CI: 1.84-12.21), impaired fasting glucose( OR=2.95, 95% CI: 1.00-8.69; OR=3.06, 95% CI: 1.04-9.02), and concurrent hypertension and impaired fasting glucose( OR=7.94, 95% CI: 3.04-20.72; OR=8.68, 95% CI: 3.28-22.94), whereas underweight young elderly had a reduced risk of hypertension( OR=0.27, 95% CI: 0.09-0.80). Elderly people in the central obesity group(WC)showed increased risk of hypertension( OR=1.39, 95% CI: 1.04-1.84)and concurrent hypertension and impaired fasting glucose( OR=2.39, 95% CI: 1.75-3.27), compared with those in the non-central obesity group.Young elderly people with central obesity had increased risk of hypertension( OR=1.46, 95% CI: 1.07-2.00), impaired fasting glucose( OR=1.62, 95% CI: 1.14-2.28), and concurrent hypertension and impaired fasting glucose( OR=3.03, 95% CI: 2.13-4.32); both elderly people and young elderly people in the central obesity group(WHtR)had increased risk of hypertension( OR=1.35, 95% CI: 1.03-1.76; OR=1.55, 95% CI: 1.13-2.14), impaired fasting glucose( OR=1.42, 95% CI: 1.04-1.94; OR=1.62, 95% CI: 1.13-2.31), and concurrent hypertension and impaired fasting glucose( OR=2.20, 95% CI: 1.60-3.02; OR=3.22, 95% CI: 2.14-4.84). In the elderly group, BMI was correlated with diastolic blood pressure and WHtR was correlated with the fasting blood glucose level. Conclusions:The levels of fasting plasma glucose and blood pressure increase with elevated physical indicator values(BMI, WC, WHtR)in the Guangxi elderly population, and the risk of developing hypertension, impaired fasting glucose, and concurrent hypertension and impaired fasting glucose increases in elderly patients with general obesity and central obesity, with a higher risk in low-aged elderly patients.

Objective:To investigate the current status of endoscopic treatment for gastroesophageal varices in portal hypertension in China, and to provide supporting data and reference for the development of endoscopic treatment.Methods:In this study, initiated by the Liver Health Consortium in China (CHESS), a questionnaire was designed and distributed online to investigate the basic condition of endoscopic treatment for gastroesophageal varices in portal hypertension in 2022 in China. Questions included annual number and indication of endoscopic procedures, adherence to guideline for preventing esophagogastric variceal bleeding (EGVB), management and timing of emergent EGVB, management of gastric and isolated varices, and improvement of endoscopic treatment. Proportions of hospitals concerning therapeutic choices to all participant hospitals were calculated. Guideline adherence between secondary and tertiary hospitals were compared by using Chi-square test.Results:A total of 836 hospitals from 31 provinces (anotomous regions and municipalities) participated in the survey. According to the survey, the control of acute EGVB (49.3%, 412/836) and the prevention of recurrent bleeding (38.3%, 320/836) were major indications of endoscopic treatment. For primary [non-selective β-blocker (NSBB) or endoscopic therapies] and secondary prophylaxis (NSBB and endoscopic therapies) of EGVB, adherence to domestic guideline was 72.5% (606/836) and 39.2% (328/836), respectively. There were significant differences in the adherence between secondary and tertiary hospitals in primary prophylaxis of EGVB [71.0% (495/697) VS 79.9% (111/139), χ2=4.11, P=0.033] and secondary prophylaxis of EGVB [41.6% (290/697) VS 27.3% (38/139), χ2=9.31, P=0.002]. A total of 78.2% (654/836) hospitals preferred endoscopic therapies treating acute EGVB, and endoscopic therapy was more likely to be the first choice for treating acute EGVB in tertiary hospitals (82.6%, 576/697) than secondary hospitals [56.1% (78/139), χ2=46.33, P<0.001]. The optimal timing was usually within 12 hours (48.5%, 317/654) and 12-24 hours (36.9%, 241/654) after the bleeding. Regarding the management of gastroesophageal varices type 2 and isolated gastric varices type 1, most hospitals used cyanoacrylate injection in combination with sclerotherapy [48.2% (403/836) and 29.9% (250/836), respectively], but substantial proportions of hospitals preferred clip-assisted therapies [12.4% (104/836) and 26.4% (221/836), respectively]. Improving the skills of endoscopic doctors (84.2%, 704/836), and enhancing the precision of pre-procedure evaluation and quality of multidisciplinary team (78.9%, 660/836) were considered urgent needs in the development of endoscopic treatment. Conclusion:A variety of endoscopic treatments for gastroesophageal varices in portal hypertension are implemented nationwide. Participant hospitals are active to perform emergent endoscopy for acute EGVB, but are inadequate in following recommendations regarding primary and secondary prophylaxis of EGVB. Moreover, the selection of endoscopic procedures for gastric varices differs greatly among hospitals.