Transplantation of insulin-producing cells derived from human MSCs to treat diabetes in a non-human primate model.

BACKGROUND: Islet cell transplantation is an emerging therapy in the treatment of diabetes mellitus. Differentiation of islet cells from mesenchymal stem cells (MSCs) is a potential solution to the challenge of insufficient donor sources. This study investigated whether human umbilical cord-derived MSCs could effectively differentiate into insulin-producing cells (IPCs) and evaluated the therapeutic efficacy of IPCs in treating diabetes. METHODS: IPCs were induced from MSCs by a two-step protocol. IPC expression products were evaluated by western blot and real-time PCR. IPC insulin secretion was evaluated by ELISA. The viability of IPCs was measured by FDA/PI and dithizone staining. The non-human primate tree shrew was used as a diabetes model. After a single STZ induction into a diabetes model, a single intraportal transplantation of IPCs, MSCs, or normal saline was performed (n = 6 per group). Blood glucose was monitored for 3 weeks, then the animals were euthanized and the distribution of IPCs in the liver was examined pathologically. RESULTS: After about 3 weeks of in vitro induction, IPCs formed microspheres of 100-200 µm, with >95% viable cells that were dithizone stain positive. IPCs expressed islet-related genes and proteins and secreted high levels of insulin whether stimulated by low or high levels of glucose. After transplantation of IPCs into diabetic tree shrews, blood glucose levels decreased rapidly to near normal and were significantly lower than the MSC or saline groups for 3 weeks thereafter. CONCLUSION: We present the novel discovery that IPCs derived from human umbilical cord MSCs exert a therapeutic effect in a non-human primate model of diabetes. This study provides a preliminary experimental basis for the use of autologous MSC-derived IPCs in the treatment of human diabetes.

Exosomal microRNAs as diagnostic biomarkers and therapeutic applications in neurodegenerative diseases.

Originating from slow irreversible and progressive loss and dysfunction of neurons and synapses in the nervous system, neurodegenerative diseases (NDDs) affect millions of people worldwide. Common NDDs include Parkinson's disease, Alzheimer's disease multiple sclerosis, Huntington's disease, and amyotrophic lateral sclerosis. Currently, no sensitive biomarkers are available to monitor the progression and treatment response of NDDs or to predict their prognosis. Exosomes (EXOs) are small bilipid layer-enclosed extracellular vesicles containing numerous biomolecules, including proteins, nucleic acids, and lipids. Recent evidence indicates that EXOs are pathogenic participants in the spread of neurodegenerative diseases, contributing to disease progression and spread. EXOs are also important tools for diagnosis and treatment. Recently, studies have proposed exosomal microRNAs (miRNAs) as the targets for therapies or biomarkers of NDDs. In this review, we outline the latest research on the roles of exosomal miRNAs in NDDs and their applications as potential diagnostic and therapeutic biomarkers, targets, and drugs for NDDs.

Correlation of c-MET expression with circulating miR-34a and miR-449 level in pancreatic cancer tissue / 中华胰腺病杂志

Objective:To investigate the correlation of c-MET expression with circulating miR-34a and miR-449 level in pancreatic cancer tissue and its clinical significance.Methods:A total of 41 patients with pancreatic cancer treated surgically and pathologically confirmed from March 2015 to March 2017 were collected in Second Affiliated Hospital of Jiaxing Medical College. The expression of hepatocyte growth factor receptor (c-MET) in pathological tissues and matching adjacent normal tissues was determined by immunohistochemistry. The patients were divided into c-MET positive group ( n=26) and c-MET negative group ( n=15) according to the results. Peripheral blood was collected before and 3 months after the operation, and the expressions of circulating miRNA34a (miR-34a) and miR-449 were determined by fluorescence quantitative PCR. The relationships between c-MET in pancreatic cancer tissue and clinicopathological features, prognosis, circulating miR-34a expression, and miR-449 expression were analyzed. The effects of circulating miR-34a and miR-449 expression on TNM stage, lymph node metastasis and prognosis of pancreatic cancer patients were analyzed. Results:The positive rate of c-MET in pancreatic cancer was obviously higher than that in adjacent normal tissue (63.4% vs 24.4%), and the difference was statistically significant ( P<0.05). Compared with c-MET negative group, the TNM stage Ⅲ/Ⅳ cases in c-MET positive group were more (73.1% vs 33.4%), the lymph node metastasis rate in c-MET positive group (76.9% vs 46.7%) were higher, and the follow-up survival time of c-MET positive group was shorter (29.5 mo vs 35 mo), and the survival rate of the c-MET positive group was lower (38.5% vs 53.3%), and the differences were statistically significant (all P<0.05). Before surgery, the expressions of circulating miR-34a and miR-449 in the c-MET positive group were lower than those in the c-MET negative group (0.228±0.068 vs 0.524±0.106, 0.252± 0.063 vs 0.432±0.094, P<0.05). After surgery, the miR-449 expression in c-MET positive group was still lower than that in c-MET negative group (0.414±0.088 vs 0.512±0.114, P<0.05), while there was no statistically significant difference on miR-34a between the two groups. Preoperative miR-34a and miR-449 expression had predictive value for TNM stage, lymphatic metastasis and prognosis ( P<0.05). Conclusions:miR-34a and miR-449 may target c-MET in pancreatic cancer tissue, which could be used as potential tumor markers for pancreatic cancer.

Analysis of mortality and leading causes of death in Chinese children under 5-year-old between 2010 and 2016 / 中华预防医学杂志

We collected death data of children under 5-year-old in China from the national child mortality surveillance system from 2010 to 2016. The change of mortality rate and causes of death were described. The mortality rate of Chinese children under 5-year-old decreased from 16.4‰ to 10.2‰ in all areas between 2010 and 2016, from 20.1‰ to 12.4 ‰ in rural areas and from 7.3‰ to 5.2‰ in urban areas, respectively, with a greater average annual decreasing rate in rural areas than urban area. During these years, in addition to traffic accidents and sepsis, other 8 cause-specific mortality rates showed a downward trend. There were substantial decreases of mortality rates of premature birth or low birth weight, birth asphyxia and neural tube defects. In urban areas, the mortality rate of premature birth or low birth weight, birth asphyxia decreased, and the mortality rate of congenital heart disease and diarrhea substantially decreased. However, there was a substantial increase of mortality rate of septicemia in urban areas. In rural areas, the change of major cause-specific mortality rates were consistent with the national trend.

Effect of sertraline on negative emotion and adverse cardiovascular events in patients with coronary heart disease complicated with depression / 中国医师进修杂志

Objective To investigate the effect of sertraline on negative emotional and adverse cardiovascular events in patients with coronary heart disease (CHD) complicated with depression. Methods The clinical data of 100 patients with CHD complicated with depression from August 2015 to August 2017 were retrospectively analyzed. The patients were divided into sertraline group and control group according to the treatment method with 50 cases each. All patients of 2 groups were treated with routine therapy of CHD and psychological intervention. The patients of sertraline group were combined with sertraline treatment, and the patients of control group were combined with shugan jieyu capsule. The improvement of negative emotion was evaluated by 17-item Hamilton depression rating scale (HAMD), and the incidence of adverse cardiovascular events was observed. The high-sensitivity c-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), endothelin-1 (ET-1) levels and sinus heart beat all the RR interphase (SDNN) before and after treatment were observed. Results The HAMD score after treatment in sertraline group was significantly lower than that in control group: (8.02 ± 1.19) scores vs. (10.57 ± 1.85) scores, and there was statistical difference (P＜0.01). The total effective rate in sertraline group was significantly higher than that in control group: 92.0% (46/50) vs. 68.0% (34/50), the incidence of the adverse cardiovascular events was significantly lower than that in control group: 4.00% (2/50) vs. 14.00% (7/50), and there were statistical differences (P＜0.05). There were no statistical differences in hs-CRP, IL-6, TNF-α and ET-1 after treatment between 2 groups (P＞0.05). The SDNN after treatment in sertraline group was significantly higher than that in control group: (111.04 ± 20.18) ms vs. (98.34 ± 23.30) ms, and there was statistical difference (P＜0.05). Conclusions Sertraline can effectively improve the depression status in patients with CHD complicated with depression, and it can reduce the incidence of adverse cardiovascular events and improve prognosis.

Trendency analysis of infant mortality rate due to premature birth or low birth weight in China from 1996 to 2013 / 中华预防医学杂志

<p><b>OBJECTIVE</b>To study the secular trend and characteristics of infant mortality rate due to premature birth or low birth weight (IMRPL) in China from 1996 to 2013.</p><p><b>METHODS</b>Data used in this study was collected from the population-based Child's Health Surveillance Network of China. The Cochran-Armitage Trend test and Poisson regression were used to test the trend of IMRPL and explore the differences of the trend among different regions or areas.</p><p><b>RESULTS</b>The nationwide IMRPL was 629.9 per 100 000 live births in 1996 and it decreased to 214.6 per 100 000 live births in 2013. The average annual decline rate was 6.14%, while the proportion of infant mortality due to premature birth or low birth weight in all infant deaths was on the rise with the average annual growth rate of 1.52%. And the proportion increased to 22.6% in 2013. IMRPLin rural and urban areas fell 28.1% and 66.6% respectively during 1996 and 2013. But the differences between urban and rural areas was obvious. During the same period, the average IMRPLin the central region was 1.40 times (95%CI:1.31-1.49) of that in the eastern region. And the average IMRPL in the western region was 2.25 times (95%CI:2.12-2.40) of that in the eastern region. The differences among different regions was obvious. Male infant mortality rate due to premature birth or low birth weight was 1.09 times (95%CI:1.05-1.14) of that in female infant from 1996 to 2013.</p><p><b>CONCLUSION</b>The risk of IMRPL decreased substantially in China from 1996 to 2013. And the risk of IMRPL decreased more in rural areas than that in urban areas. The differences among different regions and areas were obvious. Premature birth or low birth weight as one of main factors has become a serious threat for health of Chinese children.</p>

A study on rural-urban differences in neonatal mortality rate in China, 1996-2006.

OBJECTIVE: This study examined the differences in neonatal mortality rates between urban and rural areas in China. METHODS AND RESULTS: Data were taken from a database collected by the Chinese surveillance network for mortality of children under 5 years of age. The risk ratio of neonatal mortality for rural versus urban areas was between 2.2 and 2.7 for 1996-2006 and it declined to 2.0 in 2005-6. Pneumonia, birth asphyxia and preterm birth or low birth weight were the major contributors to the urban-rural differences in neonatal mortality, together with a relatively high proportion of home delivery and a relatively lower proportion of hospital treatment in rural areas. CONCLUSION: The urban-rural differences reflect the gap between the developed and the underdeveloped regions in China at that period. The neonatal mortality rate in China's rural areas could decrease further if continuous efforts are successful to increase the rates of hospital delivery in rural areas.