[Associations between 4 lipid biomarkers and cardiometabolic multimorbidity development in middle aged and old adults in China].

Objective: To estimate the longitudinal association between serum lipid biomarkers and the development of cardiometabolic multimorbidity (CMM) in middle-aged and old adults (≥45) in China, while examining effect differences among degree of dyslipidemia aggregation and various dyslipidemia combination patterns. Methods: Based on data from the China Health and Retirement Longitudinal Study (2011-2018), logistic regression analysis was used to evaluate the associations of TC, LDL-C, HDL-C, TG (4 forms of dyslipidemias), degree and pattern of dyslipidemia combination with CMM. We also used restricted cubic splines to show the dose-response associations between 4 lipid biomarkers and CMM development. Results: Of the 6 522 participants included, 590 (9.05%) developed CMM. After adjusting for covariates, all 4 forms of dyslipidemias were positively associated with CMM development (high TC: OR=1.33, 95%CI: 1.03-1.71; high LDL-C: OR=1.35, 95%CI: 1.05-1.75; low HDL-C: OR=1.45, 95%CI: 1.19-1.77; high TG: OR=1.50, 95%CI: 1.20-1.88). The U-shaped dose-response relationship between LDL-C and CMM development was observed (P for non-linear =0.022). The odds of CMM increased with the increase of dyslipidemias forms, which was highest in those with ≥3 forms of dyslipidemias (OR=2.02, 95%CI: 1.33-3.06). In various dyslipidemia form combinations, the possibility of CMM development was highest in those with high TC, high LDL-C and low HDL-C (OR=3.54, 95%CI: 1.40-8.67). High TC and high LDL-C were significantly associated with CMM development in people without cardiometabolic diseases. Low HDL-C was positively associated with diabetes and CMM development in participants without cardiometabolic diseases, cardiovascular disease (CVD) followed by diabetes, and diabetes followed by CVD. High TG was positively associated with diabetes and CMM in participants without cardiometabolic diseases, and diabetes followed by CVD. Conclusions: A total of 4 forms of dyslipidemia were all independently associated with CMM development in middle-aged and old adults in China. The dose-response relationship between LDL-C level and CMM development was U-shaped. The aggregation of 4 forms of dyslipidemia were associated with the development of CMM. Low HDL-C and high TG were significantly associated with multiple patterns of cardiometabolic diseases development.

Participation effects of workplace promoting activities on healthy eating behavior.

Objective: The study intends to examine the effect of participating healthy eating related games or activities in workplace on changes of employee's self-reported behavioral stage for adopting healthy eating. Study design: A quasi-experimental study. Methods: A multi-strategic intervention for 8-month was designed and implemented in a main staff canteen area within a non-profit academic organization. The initial event included exhibition of custom-made dining plates filled with correct portions of food models for three caloric levels and provision of user-friendly online resources, which were followed by three promotion activities (long-term exhibition of my balanced plates, matching games for six food groups, and do-it-yourself healthy plate) in the 8 months. Results: A total of 86 adult participants (males = 37, female = 49) who had completed pre- and post-surveys were included in the analysis. Participants who participated all three promotion activities presented greater advancement in stage of healthy eating behaviors (HEB) than those who did not participate any activity (ß= 1.118, 95% CI = 0.428-1.808, P = 0.001 among male participants; ß = 0.740, 95% CI = 0.145-1.336, P = 0.015 among all participants). Adjustment has been made for significantly-associated covariates including types of promotion activities, initial-HEB and gender. Conclusions: A multi-strategic intervention providing balanced food plates and online resources followed by consecutive promotion activities are effective in advancing HEB for the workplace adults. Differential impacts of promotion activities and gender should also be considered for designing workplace interventions.

[A case of atypical iris corneal endothelial syndrome].

Iridocorneal endothelial syndrome is a rare ophthalmic disease, most of which are unilateral and common in women. The rate of misdiagnosis and missed diagnosis is relatively high due to its various clinical manifestations. In this case, the patient presented uncontrollable high intraocular pressure, corneal edema leading to difficult observation of corneal endothelium morphology, and accompanied by a small amount of iris neovascularization. No clearly diagnosis was made before glaucoma surgery. Further examination was performed after corneal clearance, and the final diagnosis was iris corneal endothelial syndrome (Chandler syndrome).

A synonymous mutation in IGF-1 impacts the transcription and translation process of gene expression.

Insulin-like growth factor 1 (IGF-1) is considered to be a crucial gene in the animal development of bone and body size. In this study, a unique synonymous mutation (c.258 A > G) of the IGF-1 gene was modified with an adenine base editor to observe the growth and developmental situation of mutant mice. Significant expression differences and molecular mechanisms among vectors with different alanine synonymous codons were explored. Although modification of a single synonymous codon rarely interferes with animal phenotypes, we observed that the expression and secretion of IGF-1 were different between 8-week-old homozygous (Ho) and wild-type (WT) mice. In addition, the IGF-1 with optimal codon combinations showed a higher expression content than other codon combination modes at both transcription and translation levels and performed proliferation promotion. The gene stability and translation initiation efficiency also changed significantly. Our findings illustrated that the synonymous mutation altered the IGF-1 gene expression in individual mice and suggested that the synonymous mutation affected the IGF-1 expression and biological function through the transcription and translation processes.

[Application status and prospects of telemedicine in the field of burns].

Telemedicine refers to two or more medical institutions using communication, computer, and network technology to provide remote diagnosis, treatment, and care for patients. The necessity and feasibility of applying telemedicine are determined by the characteristics of burn injury. This paper reviewed the application of telemedicine in burn surgery at home and abroad, then analyzed the significance and problems of using this technology in the field of burns, finally forecasted the future of application of telemedicine in burn surgery.

Long non-coding RNA H19 regulates the development of gliomas through the Wnt/ß-catenin signaling pathway.

OBJECTIVE: We investigated the effects of long non-coding RNA (lncRNA) H19 on glioma cell proliferation, invasion, migration, and apoptosis and the underlying mechanisms. PATIENTS AND METHODS: H19 expression in glioma tissues, para-carcinoma tissues, and glioma cell lines was analyzed by Real-time polymerase chain reaction (RT-PCR). After transfecting U251 and U87MG cells with siRNA-H19, cell proliferation was detected by the cell counting kit-8 (CCK8) assay. Invasion and migration were detected by a transwell assay; cell cycle distribution and apoptosis were measured by flow cytometry analysis; Dvl2, GSK-3ß, cyclin D1, and ß-catenin expressions were detected by RT-PCR and Western blotting. RESULTS: H19 expression in glioma tissues was higher than that in para-carcinoma tissues and associated with poor prognosis in glioma patients. Cell proliferation, invasion, and migration significantly decreased, the percentage of glioma cells in G0/G1 significantly increased, the percentage of glioma cells in the S phase significantly decreased, and apoptosis significantly increased in U251 and U87MG cells transfected with siRNA-H19 compared to those in the siRNA-NC group. Downregulation of H19 decreased DVL2, cyclin D1, and ß-catenin expression and increased GSK-3ß expression. The inhibitory effects of downregulation of H19 on glioma cell proliferation, invasion, and migration were reversed by SKL2001 via the activation of the Wnt/ß-catenin signal pathway, which was further enhanced by inhibition of the Wnt/ß-catenin signal pathway by XAV939. CONCLUSIONS: H19 was overexpressed in glioma tissues and glioma cell lines. Downregulation of H19 inhibited cell proliferation, invasion, and migration, arrested cell cycle progression in the G0/G1 phase, and induced cell apoptosis by restraining activation of the Wnt/ß-catenin signaling pathway in glioma cells. Therefore, H19 is a potential therapeutic target for glioma therapy.

miR-375 inhibits the proliferation and invasion of glioblastoma by regulating Wnt5a.

The aberrant expression of microRNA-375 (miR-375) has been proved to be associated with carcinogenesis. However, the role of miR-375 in glioblastoma (GBM) remains unknown. The aim of this study was to investigate biological functions and its molecular mechanisms of miR-375 in GBM cells. In this study, real-time PCR results showed that the level of miR-375 expression in GBM tissues and GBM cell lines (U87 and U251) was decreased. Using MTT assay, Transwell migration and invasion assay, we demonstrated that miR-375 overexpression significantly suppress cell proliferation, cell migration and cell invasion capacity in U87 and U251 cells. However, downregulation of miR-375 had reverse effects on cell proliferation, migration and invasion. Targeting association analysis, dual luciferase assay, RT-PCR and western blot analysis results confirmed that miR-375 could target the 3'UTR of Wnt5a mRNA and regulated its protein expression. Further studies also find overexpression of Wnt5a could significantly reverse miR-375-mediated proliferation, migration and invasion on U87 and U251 cells. Therefore, we concluded that miR-375 inhibited the proliferation and invasion of GBM by regulating Wnt5a and might be a possible therapeutic agent for GBM.

RET-mediated autophagy suppression as targetable co-dependence in acute myeloid leukemia.

Many cases of AML are associated with mutational activation of receptor tyrosine kinases (RTKs) such as FLT3. However, RTK inhibitors have limited clinical efficacy as single agents, indicating that AML is driven by concomitant activation of different signaling molecules. We used a functional genomic approach to identify RET, encoding an RTK, as an essential gene in multiple subtypes of AML, and observed that AML cells show activation of RET signaling via ARTN/GFRA3 and NRTN/GFRA2 ligand/co-receptor complexes. Interrogation of downstream pathways identified mTORC1-mediated suppression of autophagy and subsequent stabilization of leukemogenic drivers such as mutant FLT3 as important RET effectors. Accordingly, genetic or pharmacologic RET inhibition impaired the growth of FLT3-dependent AML cell lines and was accompanied by upregulation of autophagy and FLT3 depletion. RET dependence was also evident in mouse models of AML and primary AML patient samples, and transcriptome and immunohistochemistry analyses identified elevated RET mRNA levels and co-expression of RET and FLT3 proteins in a substantial proportion of AML patients. Our results indicate that RET-mTORC1 signaling promotes AML through autophagy suppression, suggesting that targeting RET or, more broadly, depletion of leukemogenic drivers via autophagy induction provides a therapeutic opportunity in a relevant subset of AML patients.

An RNAi-based screen reveals PLK1, CDK1 and NDC80 as potential therapeutic targets in malignant pleural mesothelioma.

This corrects the article DOI: 10.1038/bjc.2017.85.

The application of traffic-light food labelling in a worksite canteen intervention in Taiwan.

OBJECTIVE: This study evaluated customer attitudes, perceptions, and utilisation of a traffic-light food labelling (TFL) programme before and after the TFL was implemented in a worksite canteen in Taiwan. STUDY DESIGN: A one-arm intervention was implemented in the canteen and buffet of a research park in Taiwan. Phase 1 consisted of dissemination of information regarding the TFL, targeting the customers (June-July, 2014); phase 2 consisted of implementation of the TFL in the buffet starting in August 2014. The TFL included red, yellow and green labels, indicating 'unhealthy/stop', 'moderately unhealthy/wait' and 'healthy/go', respectively. METHODS: The evaluation was based on two independent anonymous surveys in July 2014 (in phase 1) and April 2015 (in phase 2). Customers were invited to take a survey regarding the TFL programme, the food environment in the canteen, and their lunch choices. Logistic regression models examined the changes in customers' attention and attitudes towards the labelling and their food choices between the two surveys. RESULTS: The customers reported positive attitudes towards the TFL. The proportion of customers who reported choosing foods based on the recommendations increased from 38% to 50% (P < 0.01). The proportion of the buffet customers who chose green-light entrées and red-light entrées changed from 13% and 63% to 36% and 21%, respectively (P < 0.001). The availability of green-light entrées in the buffet increased as well. CONCLUSIONS: This first report of a TFL intervention in an Asian worksite suggests that TFL is acceptable and well understood by this population and may assist customers in choosing healthier items when healthier choices are available.

Elevated serum retinol-binding protein 4 levels are correlated with blood pressure in prehypertensive Chinese.

Retinol-binding protein 4 (RBP4) has been reported involving in the occurrence and development of hypertension. However, to date, few data are available on the correlation between serum RBP4 level and blood pressure (BP) in prehypertension. Therefore, this association was investigated in prehypertensive Chinese. Overall, 160 subjects with prehypertension (Pre-HT group) and 160 subjects with normal BP (NBP group) were recruited in this study. The subjects were divided into the following four subgroups according to body mass index (BMI): obese Pre-HT subgroup; non-obese Pre-HT subgroup; obese NBP subgroup; and non-obese NBP subgroup (n=80 in each). Anthropometric parameters, systolic BP (SBP), diastolic BP (DBP) and several biochemical parameters were measured. Fasting insulin was evaluated by radioimmunoassay. Serum RBP4 level was measured by enzyme-linked immunosorbent assay. The Pre-HT group had higher levels of serum RBP4 level than did the NBP group (P<0.001). Moreover, higher RBP4 levels were identified in the obese Pre-HT subgroup relative to the non-obese Pre-HT subgroup (P=0.005). However, no difference in RBP4 level was identified between the obese and the non-obese NBP subgroups (P=0.317). RBP4 level was positively correlated with BMI (r=0.226, P=0.001), SBP (r=0.468, P<0.001) and DBP (r=0.358, P<0.001) after adjustment for age, sex, smoking status and alcohol consumption. The results of the multiple regression analyses demonstrated that RBP4 level was independently associated with SBP (ß=0.427, P<0.001) and DBP (ß=0.338, P<0.001). In conclusion, serum RBP4 level was significantly higher and closely associated with BP in prehypertensive Chinese.

Multiple variants in 5q31.1 are associated with systemic lupus erythematosus susceptibility and subphenotypes in the Han Chinese population.

BACKGROUND: A previous study provided evidence for a genetic association between PPP2CA on 5q31.1 and systemic lupus erythematosus (SLE) across multi-ancestral cohorts, but failed to find significant evidence for an association in the Han Chinese population. OBJECTIVES: To explore the association between this locus and SLE using data from our previously published genome-wide association study (GWAS). METHODS: Single-nucleotide polymorphisms (SNPs) rs7726414 and rs244689 (near TCF7 and PPP2CA in 5q31.1) were selected as candidate independent associations from a large-scale study in a Han Chinese population consisting of 1047 cases and 1205 controls. Subsequently, 3509 cases and 8246 controls were genotyped in two further replication studies. We then investigated the SNPs' associations with SLE subphenotypes and gene expression in peripheral blood mononuclear cells. RESULTS: Highly significant associations with SLE in the Han Chinese population were detected for SNPs rs7726414 and rs244689 by combining the genotype data from our previous GWAS and two independent replication cohorts. Further conditional analyses indicated that these two SNPs contribute to disease susceptibility independently. A significant association with SLE, age at diagnosis < 20 years, was found for rs7726414 (P = 0·001). The expression levels of TCF7 and PPP2CA messenger RNA in patients with SLE were significantly decreased compared with those in healthy controls. CONCLUSIONS: This study found evidence for multiple associations with SLE in 5q31.1 at genome-wide levels of significance for the first time in a Han Chinese population, in a combined genotype dataset. These findings suggest that variants in the 5q31.1 locus not only provide novel insights into the genetic architecture of SLE, but also contribute to the complex subphenotypes of SLE.

The correlation between children's status asthmatics and interstitial lung disease.

OBJECTIVE: Investigating the correlation between children's status asthmatics and interstitial lung disease (ILD). PATIENTS AND METHODS: We continuously selected 20 cases of children's status asthmatics combined with ILD (group A), 20 cases of pure status asthmatics (group B), 20 cases of pure ILD (group C) and 20 cases of healthy children (group D). We measured Th1/Th2 by flow cytometry as well as the level of expression of hs-CRP, IL-7 cytokines (TSLP), monocyte chemoattractant protein-1 (MCP-1) and anti-Jo-1 antibody by ELISA method. RESULTS: Th1 and Th1/Th2 of groups A and B were significantly lower than those of group C and D. Th2 was significantly (p<0.05) higher than that of groups C and D. The level of expression of hs-CRP, TSLP, MCP-1 and anti-Jo-1 antibody in the groups A and B were all significantly higher (p<0.05) than those of groups C and D. There were differences of the above index of the comparison between groups A and B, but no difference between groups C and D. CONCLUSIONS: Children's status asthmatics and ILD may correlate with the abnormal expression of Th1/Th2, hs-CRP, TSLP, MCP-1 and anti-Jo-1 antibody.

Linkage analysis of SNPs in IGFBP-6 and its relation with the body sizes of pig.

Insulin-like growth factor binding protein-6 (IGFBP-6) is a member of the IGFBP family, which is known to be a key factor in regulating the effect of insulin-like growth factor-2 (IGF-2) on the animal growth and development. Gene sequences of 3'-untranslated regions (UTR) and exon 4 of IGFBP-6 may influence the expression and proteolysis of IGFBP-6. In this study, 551 bp of the IGFBP-6 (including 257 bp of intron 3, exon 4, and 170 bp of 3' UTR) were sequenced and compared in the Bama and Tibetan mini-pigs, the Landrace and Large White pigs, and the Northeast wild boars. Six single nucleotide polymorphisms (SNPs) were detected in the IGFBP-6, in which T593C, T636C, and T745C were in intron 3, A67G was in exon 4, and G37A was in 3' UTR. T636C, T745C, and A67G were in linkage and formed four kinds of haplotypes, with CCT being the dominant haplotype in the mini-pigs; however, the haplotype block was not formed in the Landrace pigs and Large White pigs or the Northeast wild boars. Based on the above results, we concluded that the SNPs and haplotype of the IGFBP-6 may be related to the mini-size formation of the pig.

Identifying significant crosstalk of pathways in tuberous sclerosis complex.

OBJECTIVE: Tuberous sclerosis complex (TSC) is the second most common phakomatosis and is characterized by the formation of benign hamartomas and low-grade neoplasms in multiple organ systems. In this study, our objective here was to explore the interaction and crosstalk between pathways in response to tuberous sclerosis complex. MATERIALS AND METHODS: We enriched the significant pathways and made the crosstalk analysis of the significant pathways. RESULTS: The results showed that ECM-receptor interaction was a significant pathway in TSC. In addition, insulin-signaling and mTOR signaling also have been identified involved in TSC here, which have been well characterized. Further analysis indicated that there was a crosstalk between ECM-receptor interaction and antigen processing and presentation, ECM-receptor interaction and apoptosis, and leishmaniasis-oxidative phosphorylation-pancreatic cancer. In this study, a network-based approach was used to analyze the crosstalk among TSC related pathways. The crosstalk of pathways is found and analyzed using the PPI datasets and expression profiles. CONCLUSIONS: Our work showed that comprehensive and system-wide analysis could provide evidence for TSC pathway and complement the traditional component-based approaches. The crosstalk identified might provide new alternative insights into the TSC pathology, which may contribute to the development of novel therapeutic targets for TSC.

An RNAi-based screen reveals PLK1, CDK1 and NDC80 as potential therapeutic targets in malignant pleural mesothelioma.

BACKGROUND: Malignant pleural mesothelioma (MPM) is an aggressive tumour originating in the thoracic mesothelium. Prognosis remains poor with 9- to 12-month median survival, and new targets for treatments are desperately needed. METHODS: Utilising an RNA interference (RNAi)-based screen of 40 genes overexpressed in tumours, including genes involved in the control of cell cycle, DNA replication and repair, we investigated potential therapeutic targets for MPM. Following in vitro characterisation of the effects of target silencing on MPM cells, candidates were assessed in tumour samples from 154 patients. RESULTS: Gene knockdown in MPM cell lines identified growth inhibition following knockdown of NDC80, CDK1 and PLK1. Target knockdown induced cell-cycle arrest and increased apoptosis. Using small-molecule inhibitors specific for these three proteins also led to growth inhibition of MPM cell lines, and Roscovitine (inhibitor of CDK1) sensitised cells to cisplatin. Protein expression was also measured in tumour samples, with markedly variable levels of CDK1 and PLK1 noted. PLK1 expression in over 10% of cells correlated significantly with a poor prognosis. CONCLUSION: These results suggest that RNAi-based screening has utility in identifying new targets for MPM, and that inhibition of NDC80, CDK1 and PLK1 may hold promise for treatment of this disease.

Restoring expression of miR-16: a novel approach to therapy for malignant pleural mesothelioma.

BACKGROUND: Malignant pleural mesothelioma (MPM) is recalcitrant to treatment and new approaches to therapy are needed. Reduced expression of miR-15/16 in a range of cancer types has suggested a tumour suppressor function for these microRNAs, and re-expression has been shown to inhibit tumour cell proliferation. The miR-15/16 status in MPM is largely unknown. MATERIALS AND METHODS: MicroRNA expression was analysed by TaqMan-based RT-qPCR in MPM tumour specimens and cell lines. MicroRNA expression was restored in vitro using microRNA mimics, and effects on proliferation, drug sensitivity and target gene expression were assessed. Xenograft-bearing mice were treated with miR-16 mimic packaged in minicells targeted with epidermal growth factor receptor (EGFR)-specific antibodies. RESULTS: Expression of the miR-15 family was consistently downregulated in MPM tumour specimens and cell lines. A decrease of 4- to 22-fold was found when tumour specimens were compared with normal pleura. When MPM cell lines were compared with the normal mesothelial cell line MeT-5A, the downregulation of miR-15/16 was 2- to 10-fold. Using synthetic mimics to restore miR-15/16 expression led to growth inhibition in MPM cell lines but not in MeT-5A cells. Growth inhibition caused by miR-16 correlated with downregulation of target genes including Bcl-2 and CCND1, and miR-16 re-expression sensitised MPM cells to pemetrexed and gemcitabine. In xenograft-bearing nude mice, intravenous administration of miR-16 mimics packaged in minicells led to consistent and dose-dependent inhibition of MPM tumour growth. CONCLUSIONS: The miR-15/16 family is downregulated and has tumour suppressor function in MPM. Restoring miR-16 expression represents a novel therapeutic approach for MPM.

Inhibition of CYP3A mRNA and protein expression, and enzymatic activity, by enrofloxacin in chickens.

This study was to investigate the effect of enrofloxacin (EF) on CYP3A in chicken by using quantitative reverse transcription-polymerase chain reaction and immunodetected. The treated chickens were given 5, 25 and 125 mg/kg of EF while the control chickens were treated with the same volume saline. There was no significant difference between the low dose group and controls in the concentration of hepatic microsome protein and total CYP content, while the middle and high dose EF caused the down regulation. Depression of the CYP3A activity, mRNA and protein were observed in treated chickens, and the inhibition degree was different from each group. It was concluded that EF caused the inhibition of CYP3A both in genetic transcription and protein levels. But the inhibition metabolism still needs further researches.

Effects of varicocele upon the expression of apoptosis-related proteins.

Varicocele-associated apoptosis has been recognised as a cause of male infertility. Thus, we assessed the expression of somatic apoptosis-related proteins (the typical protein-dependent apoptosis markers) in ejaculated sperm plasma from both patients with varicocele and normal donors. We evaluated the relationships between certain apoptosis-related proteins and normal semen quality. Semen samples were obtained from 25 patients with varicocele and from 10 normal fertile controls. These samples were compared using computer-assisted semen analysis for motion parameters and manual analysis for morphology, and were also assayed for apoptosis-related protein activation including caspase-3, poly-ACP-ribose polymerase (PARP), the Bcl-2 family (Bcl-2, Bak) and p53 by means of immunoblot analysis. PARP, Bak and p53 were expressed substantially more in the sperm cells of the varicocele group when compared with the normal group (P < 0.05). The expression of caspase-3 and Bcl-2 did not appear to differ between these two study groups. An increased expression of PARP, Bak and p53 for varicocele-afflicted individuals indicated an increased participation by these agents in the regulating of apoptosis in the ejaculated semen from patients with varicocele, suggesting that certain protein-development apoptotic mechanisms might originate in the cytoplasmic droplet or within mitochondria of spermatocytes and then might function within the nucleus of the cell.