Transplantation of human induced pluripotent stem cell derived keratinocytes accelerates deep second-degree burn wound healing.

BACKGROUND: Current evidence shows that human induced pluripotent stem cells (hiPSCs) can effectively differentiate into keratinocytes (KCs), but its effect on skin burn healing has not been reported. AIM: To observe the effects of hiPSCs-derived KCs transplantation on skin burn healing in mice and to preliminarily reveal the underlying mechanisms. METHODS: An analysis of differentially expressed genes in burn wounds based on GEO datasets GSE140926, and GSE27186 was established. A differentiation medium containing retinoic acid and bone morphogenetic protein 4 was applied to induce hiPSCs to differentiate into KCs. The expression of KCs marker proteins was detected using immunofluorescence staining. A model of a C57BL/6 mouse with deep cutaneous second-degree burn was created, and then phosphate buffered saline (PBS), hiPSCs-KCs, or hiPSCs-KCs with knockdown of COL7A1 were injected around the wound surface. The wound healing, re-epithelialization, engraftment of hiPSCs-KCs into wounds, proinflammatory factor level, and the NF-κB pathway proteins were assessed by hematoxylin-eosin staining, carboxifluorescein diacetate succinimidyl ester (CFSE) fluorescence staining, enzyme linked immunosorbent assay, and Western blotting on days 3, 7, and 14 after the injection, respectively. Moreover, the effects of COL7A1 knockdown on the proliferation and migration of hiPSCs-KCs were confirmed by immunohistochemistry, EdU, Transwell, and damage repair assays. RESULTS: HiPSCs-KCs could express the hallmark proteins of KCs. COL7A1 was down-regulated in burn wound tissues and highly expressed in hiPSCs-KCs. Transplantation of hiPSCs-KCs into mice with burn wounds resulted in a significant decrease in wound area, an increase in wound re-epithelialization, a decrease in proinflammatory factors content, and an inhibition of NF-κB pathway activation compared to the PBS group. The in vitro assay showed that COL7A1 knockdown could rescue the inhibition of hiPSCs-KCs proliferation and migration, providing further evidence that COL7A1 speeds up burn wound healing by limiting cell proliferation and migration. CONCLUSION: In deep, second-degree burn wounds, COL7A1 can promote KC proliferation and migration while also suppressing the inflammatory response.

[Empirical research of measuring elderly health utility in the outskirts of Beijing by using European quality of life 5-dimensions].

OBJECTIVE: To evaluate health utility values of the elderly in the outskirts of Beijing by European quality of life 5-dimensions (EQ-5D) from the EuroQol Group, and to compare the health utility values by using different translation models. METHODS: In the cross-sectional study, EQ-5D was used to measure the quality of life for 65 to 79 year-old usual residents in the town of Qinglonghu and Zhoukoudian in Fangshan District of Beijing. The health index which represented the health utility was calculated by using the Japan, the United Kingdom (UK), the United States (US) population-based time trade-off (TTO) models. Kruskal-Wallis H test was adopted to compare the health indexes calculated by the different models, and intraclass correlations coefficients (ICCs) and Bland-Altman plot were used to evaluate the consistency of the utility calculated by the three models. Mann-Whitney U test was used to compare the impacts of Cardio-vascular diseasel (CVD) on the 3 kinds of health index. The Spearman rho correlation coefficients between the 3 kinds of health index, EQ-VAS (visual analogue scales) score and age, gender, health status were also calculated. RESULTS: There were 2 406 participants in this analysis, with a mean age of 70.3 years, of whom 34.3% were male. The median and quantile range of Japan weights, US weights and UK weights health indexes were 1 (0.28), 1 (0.24) and 1 (0.29), respectively. The minimum and maximum of the three indexes were -0.06/1, -0.43/1 and -0.03/1, respectively. The US weights yielded the highest scores and the UK weights the lowest scores. The Japan, US and UK weight scores differed from each other (P<0.005). The Japan and US scores had the highest ICCs (0.987, 95%CI 0.986-0.988), followed by the US and UK scores (0.941, 95%CI 0.937- 0.946) and then the Japan and UK scores (0.921, 95%CI 0.915-0.927). The difference scores of 96.9%, 95.1% and 95.0% were found between the limits of agreement in Bland-Altmand plot. Negative correlations existed between the US/UK score and the number of CVDs, but not existed between the Japan score and the number of CVDs. CONCLUSION: The health indexes calculated by using the different EQ-5D TTO transform models were different for the elderly people in the Beijing suburban district, TTO model based on Chinese health preference should be developed.

[Gender-specific differences in relative effects of cardiovascular risk factors among rural population].

OBJECTIVE: To investigate the prevalence and association of cardiovascular disease and its risk factors in Fangshan District, Beijing. METHODS: A total of 7 577 rural residents aged over 40 years were surveyed to estimate the prevalence of cardiovascular disease and its risk factors by questionnaire survey, physical examination and biochemical measures. The prevalence odds ratio (POR) was calculated for the association of stroke / coronary heart disease (CHD) with its risk factors in multiple logistic regression models. RESULTS: Prevalence of CHD, stroke, diabetes, hypertension, dyslipidemia, overweight and obesity was presented as 6.5%, 4.1%, 10.7%, 39.5%, 56.7%, 44.0% and 13.6%, respectively. In the adjusted multiple logistic regression models, hypertension showed stronger association with stroke (POR=2.780, 95%CI: 2.146-3.602), while diabetes had a higher correlation with CHD (POR=2.671, 95%CI: 2.121-3.363). After stratification by gender, significant risk factors for stroke were overweight / obesity (POR=1.652, 95%CI: 1.122-2.433), body mass index (POR=1.048, 95%CI: 1.002- 1.096), systolic blood pressure (POR=1.017, 95%CI: 1.005-1.030) and serum glucose (POR=1.093, 95%CI: 1.048-1.140) in females, whereas dyslipidemia (POR=1.615, 95%CI: 1.124-2.319), total cholesterol (POR=3.932, 95%CI: 1.533-10.086) and high-density lipoprotein cholesterol (POR=0.072, 95%CI: 0.022-0.236) were associated with stroke in males. CONCLUSION: Highly prevalent cardiovascular risk factors aggravated the burden brought by stroke and CHD in the rural population, and the various risk factors for stroke and CHD exhibited heterogeneous contributions among the population with different gender.

Evaluation of the efficacy and safety of a neoadjuvant gemcitabine and nedaplatin regimen followed by radiotherapy or concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma.

The aim of the present study was to evaluate the efficacy and safety of a neoadjuvant gemcitabine and nedaplatin chemotherapy regimen, followed by concurrent chemoradiotherapy or radiotherapy alone, in locoregionally advanced nasopharyngeal carcinoma (NPC). Eighty-six patients with stage III, IVA or IVB NPC, who received neoadjuvant chemotherapy [gemcitabine, 1,000 mg/m2 on day 1 (d1) and d5; nedaplatin, 25 mg/m2 on d 1-3] every 3 weeks for at least two cycles, followed by intensity-modulated radiotherapy every 3 weeks, with or without concurrent nedaplatin (25 mg/m2, d1-3) between September 2010 and December 2013, were retrospectively analyzed. By comparing pretreatment and post-treatment MRI images, it was shown that seven patients achieved a complete response (8.5%), while 66 achieved a partial response (80.5%), following completion of neoadjuvant chemotherapy (combined response rate, 89.0%). Grade 3-4 toxicities following neoadjuvant chemotherapy included neutropenia (29.1%), leukopenia (11.6%), liver dysfunction (9.3%), thrombocytopenia (9.3%) and nausea/vomiting (8.1%). The median follow-up was 18 months (range, 5-44 months). The 2-year relapse-free survival, distant metastasis-free survival, progression-free survival and overall survival rates were 96.6, 85.4, 83.3 and 96.1%, respectively. Compared with alternative neoadjuvant chemotherapy regimens in combination with radiotherapy or concurrent chemoradiotherapy, the present gemcitabine and nedaplatin did not provide additional survival benefit and led to a higher frequency of liver dysfunction. Therefore, neoadjuvant gemcitabine and nedaplatin should be used with caution in locoregionally advanced NPC.

[Influence of chronic diseases on health related quality of life in middle-aged and elderly people from rural communities: application of EQ-5D scale on a Health Survey in Fangshan, Beijing].

OBJECTIVE: To evaluate the health related quality of life (HRQoL) and to explore the influencing factors related to the prevalence of the essential hypertension, diabetes, coronary heart disease (CHD) and stroke in middle-aged and elderly people from rural communities. METHODS: A total of 5345 individuals were chosen from a 2010 Health Survey in Fangshan, Beijing. Self-designed questionnaire was applied to collect the information on general health-related behaviors, chronic conditions, self-rated health, blood pressure and HRQoL with the EuroQoL questionnaire (EQ-5D) were measured. Probit regression model was used to identify the influencing factors on HRQoL, adjusting age, marriage status, education level, smoking, alcohol intake, physical activity and control of blood pressure. Population Attributable Risk Proportion (PARP) for estimating the influence of chronic disease on HRQoL was also calculated. RESULTS: The average EQ-5D index was 0.923 ± 0.145, with 72.1% of the overall respondents in the status of having chronic diseases. Participants with chronic diseases had significantly lower EQ-5D index (0.907 ± 0.155) than those without (0.963 ± 0.105) (t = 15.082, P < 0.001). Significant relations were found between a lower HRQoL and chronic diseases. Relative risk (RR) and 95% confidence interval (95%CI) of poor HRQoL in populations with hypertension, diabetes, CHD and stroke were 1.686 (95%CI: 1.519 - 1.871), 1.725 (95%CI: 1.502 - 1.981), 1.869 (95%CI: 1.663 - 2.099), and 1.759 (95%CI: 1.474 - 2.089) respectively. The most influential disease appeared to be stroke in male (RR = 1.929, 95%CI: 1.462 - 2.546), whereas CHD in female individuals (RR = 1.926, 95%CI: 1.671 - 2.220). Rates of PARP (PAR%) for poor HRQoL in chronic disease subgroups were as follow: hypertension 31.05%, CHD 23.39%, diabetes 4.84% and stroke 4.44%, respectively. CONCLUSION: This study suggested that stroke, at individual level, was the major influential factor to HRQoL. However, hypertension remained the leading preventable influential factor to HRQoL at the population level.