[A study on the association between insulin resistance and genome-wide DNA methylation based on Shanghai monozygotic twins].

Objective: To explore the association between insulin resistance (IR) and genome-wide DNA methylation based on Shanghai twin study. Methods: Monozygotic twins (MZ) from Shanghai were recruited during 2012-2013, 2017-2018, and 2022-2023. Data were collected by questionnaire survey, physical examination and laboratory tests. Genome-wide DNA methylation was quantified. Generalized linear mixed effect model was applied to analyze the association between methylation level at each site and homeostatic model assessment 2-insulin resistance (HOMA2-IR). Non-paired and paired designs were used to assess the association between DNA methylation and phenotype of IR. Cluster analysis was conducted to identify the clusters of top significant sites. Generalized linear regression was performed to examine the differential methylation patterns from clusters. Results: A total of 100 MZ pairs were included in this study. Hypermethylated cg10535199-2q23.1 (ß=0.74%, P=1.51×10-7, OR=1.06, 95%CI: 1.03-1.09) and ch.17.49619327-SPOP (ß=0.23%, P=7.54×10-7, OR=1.17, 95%CI: 1.08-1.28) were identified with suggestive significance. After correcting for multiple testing, no sites reached genome-wide significance. There was no statistical significance in the paired analysis. Two clusters with hypomethylated (ß=-0.39%, P<0.001) and hypermethylated (ß=0.47%, P<0.001) patterns were observed for HOMA2-IR. Conclusions: IR was significantly associated with DNA methylation, and genetic factors might contribute to the association.

[A case-control study on the association between a healthy lifestyle and obesity among adult twins in Shanghai].

Objective: To investigate the associations between the numbers of healthy lifestyles and overweight/obesity and abdominal obesity in adult twins in Shanghai. Methods: Based on the Shanghai Twin Registry System Phase Ⅱ survey data in 2017-2018, a case-control study was conducted to analyze the association between healthy lifestyles and obesity and further adjusted for confounders by a co-twin control study. Results: A total of 7 864 adult twins (3 932 pairs) were included. In the co-twin case-control analysis for monozygotic twins, compared with participants with 0 to 2 healthy lifestyles, those with 3 and 4 to 5 healthy lifestyles had a 49% (OR=0.51, 95%CI: 0.28-0.93) and 70% (OR=0.30, 95%CI: 0.13-0.69) lower risk of overweight/obesity, respectively, and a 17% (OR=0.83, 95%CI: 0.44-1.57) and 66% (OR=0.34, 95%CI: 0.14-0.80) lower risk of abdominal obesity, respectively. For each additional healthy lifestyle, the risk of developing overweight/obesity was reduced by 41% (OR=0.59, 95%CI: 0.42-0.85), and the risk of developing abdominal obesity was reduced by 37% (OR=0.63, 95%CI: 0.44-0.90). Conclusion: An increasing number of healthy lifestyles was associated with a marked decreased risk for both overweight/obesity and abdominal obesity.

[Analysis of PKD1 gene mutation in a pedigree affected with autosomal dominant polycystic kidney disease].

Objective: To analyze the clinical phenotype and detect the pathogenic gene in a Chinese pedigree with autosomal dominant polycystic kidney disease(ADPKD). Methods: The proband of this study was hospitalized in Dongguan City People's Hospital on October 10, 2017, due to "left maxillary apical cyst". Clinical phenotypes were noted, imaging examinations and determination of biochemical indicators were carried out for the clinical diagnosis of the proband. Genomic DNA was extracted from peripheral venous blood. Whole-exome genotyping of the proband was performed with the next generation sequencing technology, and the candidate mutation site of the patient and his family members was verified by PCR and Sanger sequencing technology. The mutation site was further screened in 150 unrelated healthy Chinese controls. Mutation frequency within human populations and bioinformatics analysis were predicted with softwares including ExAC, dbSNP, HGMD, 1000 genomes, ClinVar, PKDB, Mutation Taster and PhyloP. Results: The proband, a 46-year-old male, was diagnosed with hypertension, positive urine occult blood and elevated blood creatinine. B-ultrasound and CT examinations showed that he had bilateral polycystic kidney with left kidney stones and polycystic liver. The gene analysis showed that the c.11017-10C>A heterozygous splice mutation in PKD1 gene was identified in the proband, his second younger brother, younger sister, daughter and niece, but absent in 150 healthy controls. Bioinformatics analysis showed it has been reported in the dbSNP, ClinVar, HGMD, PKDB and Mutation Taster databases. Some databases predicted it has a harmful function for probably leading to production of a truncated polycystin1(PC1) protein. Conclusion: c.11017-10C>A underlies the Chinese ADPKD pedigree and expands mutation spectrum of PKD1.

MiR-127-3p targets KIF3B to inhibit the development of oral squamous cell carcinoma.

OBJECTIVE: Recently, increased microRNAs have been shown to play an important role in the pathogenesis and progression of human cancers, including oral squamous cell carcinoma (OSCC). In this study, we focused on the function of microRNA-127-3p (miR-127-3p) associated with OSCC carcinogenesis. PATIENTS AND METHODS: MiR-127-3p and KIF3B expressions were observed via quantitative Real-time polymerase chain reaction (qRT-PCR) or Western blot in OSCC. The functions of mR-127-3p and KIF3B were investigated through MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and transwell assays. And luciferase reporter assay was performed to confirm the relationship between mR-127-3p and KIF3B. RESULTS: First, down-regulation of miR-127-3p was identified in OSCC, which was associated with malignant clinicopathological features and poor prognosis in OSCC patients. Functionally, overexpression of miR-127-3p led to inhibition of cell proliferation and metastasis in OSCC. Further, KIF3B was confirmed to be a direct target of miR-127-3p. Moreover, upregulation of KIF3B was also observed in OSCC, which promoted tumorigenesis of OSCC. In particular, the upregulation of KIF3B partially attenuated the inhibitory effect of miR-127-3p on the development of OSCC. CONCLUSIONS: MiR-127-3p targeted KIF3B to inhibit the development of OSCC through suppressing cell proliferation, migration and invasion.

[General plan of Shanghai Diet and Health Survey].

Shanghai Diet and Health Survey (SDHS) was designed to prospectively access local residents' food consumption, energy and nutrient intake, related chemical contaminant exposure, and the seasonal change trend to explore the relationship of diet with health. Data from SDHS can be used as fundamental information and scientific evidences for the development of local nutrition and food safety policies.

[Dietary pattern and its seasonal characteristic in residents of Shanghai, 2012-2014].

Objective: To analyze dietary pattern and its seasonal characteristic in residents of Shanghai. Methods: A representative sample was surveyed and followed up in four different seasons during 2012-2014. Information of food consumption was collected by 3-day 24-hour dietary recall and condiments weighing method. The intake of energy and macronutrients were calculated according to the Chinese Food Composition Table. Results: Annual average daily intake was 191.09 g for grain, 250.69 g for vegetable, 107.23 g for fruit, 223.53 g for animal food, 96.39 g for dairy products, 11.19 g for soy bean and its product, 36.54 g for cooking oil, and 7.57 g for salt. Significant differences were observed in food consumption among different seasons (P<0.05). Annual average daily intake of energy was 2 048.70 kcal, carbohydrates was 241.04 g, protein was 82.35 g, fat was 85.99 g and proportion of energy contributed by fat was 37.99%. Different seasons, age, residential areas, and income were influence factors for food consumption (P<0.05). Conclusions: Energy intake was adequate in residents of Shanghai. Unhealthy dietary pattern, including high proportion of fat and consumption of cooking oil and salt (lower than average intake of large cities, but higher than recommendation), was observed. It is necessary to take appropriate nutrition intervention, and future researches on dietary intake should consider seasonal influences.

[Dairy product intake and influencing factors in residents of Shanghai].

Objective: To understand the dairy product intake in residents of Shanghai, its seasonal changes and the influencing factors. Methods: A group of representative residents was surveyed and followed up in four seasons in Shanghai during 2012-2014. Information of the dairy product intake was collected by food frequency questionnaire. Results: Liquid milk and yogurt were the main dairy products consumed by the residents of Shanghai. The annual dairy product intake rate was 41.8%, and the median of dairy intake of milk was 145.3 g/d, accounting for 48.4% of reference dietary intake value, and only 4.5% of people's diary product intake reached intake reference value. The area specific differences in intake rate of liquid milk, yogurt and total dairy product intake were significant in four seasons and in whole year (P<0.05). The area specific differences in total dairy product intake were significant (P<0.05) in spring, summer and winter. In general, it was shown that dairy product intake in urban area was higher than that in suburban area and in rural area. The data of Shanghai and urban area showed that the total dairy product intake was significant different among four seasons (P<0.05), but no significant difference was observed among four seasons in suburban and rural areas. The logistic regression analysis results showed that people with average household income higher than local average level or higher education levels were more likely to consume dairy products daily. People who reported to have good health status or sleep quality were more likely to drink milk compared to those who have worse health status or sleep quality (P<0.05). Conclusions: Even though dairy product intake rate and volume have been improved in residents in Shanghai, it is still stay at lower level, especially in rural area. To promote consumption of dairy products, it is necessary to control diary product price from macro perspective, and strengthen healthy education about the importance of dairy product intake and guide residents to select suitable dairy products.

[Investigation of doctors' and nurses' perceptions and implementation of delirium management in intensive care unit].

Objective: To investigate doctors' and nurses' perceptions and implementation of delirium management in intensive care unit. Methods: A total of 197 doctors and nurses in 2 general ICUs and 3 special ICUs at Peking Union Medical College Hospital finished a self-designed questionnaire of delirium management. Results: There were 47 males and 150 females, 43 doctors and 154 nurses who participated in the survey.One hundred and twenty five participators were from general ICU and the others from special ICU. The ICU staff had a significant difference on the perceptions and implementation of delirium management(P< 0.001) including. Doctors and nurses scored lowest in "family engagement and empowerment" and "sleep management" with (4.620±2.393) and (5.430±2.153) respectively. There was a significant difference between nurses and doctors in the management of analgesia and sedation (P< 0.05).Doctors and nurses from different ICUs had significant discrepancy in the implementation of "delirium assessment" (P< 0.05). Conclusions: The ICU staff should improve the perceptions and the implementation of delirium management,especially in special ICUs. Delirium management should be included as a routine care in ICU to improve patients' outcome.

In vitro transcription directed from the somatostatin promoter is dependent upon a purified 43-kDa DNA-binding protein.

In vitro transcription analyses were used to establish the biological function of a 43-kDa affinity-purified DNA-binding protein. The 43-kDa affinity-purified protein protects the region from position -59 to position -35 of the somatostatin promoter from DNase I digestion. This region of the somatostatin promoter harbors the TGACGTCA motif, also found and required for function in a number of other cAMP-responsive and adenovirus E1A-inducible promoters. Efficient and authentic transcription in vitro directed from the somatostatin promoter requires the TGACGTCA promoter element. In vitro transcription assays performed in the presence of somatostatin (positions -60 to -29), enkephalin (positions -105 to -71), and adenovirus type 5 E3 gene (positions -72 to -42) competitor fragments, harboring similar TGACGTCA motifs, selectively inhibit transcription directed from the somatostatin promoter, suggesting that the TGACGTCA element is the site of interaction of a somatostatin gene transactivator. Furthermore, extracts depleted of the TGACGTCA-binding activities by affinity chromatography utilizing a biotinylated oligonucleotide-avidin resin, are incapable of directing transcription from the somatostatin but not from the adenovirus major late promoter. Addition of the purified 43-kDa protein to the affinity-depleted extract restores transcription from the somatostatin promoter. These results are consistent with the 43-kDa protein being a trans-activator of the somatostatin gene.