Mir-142-3P regulates MAPK protein family by inhibiting 14-3-3η to enhance bone marrow mesenchymal stem cells osteogenesis.

Clinical studies have found 14-3-3η to be associated with osteoporosis through undefined mechanisms. We aimed to investigate the role of 14-3-3η in osteoporosis and its potential associations with miRNAs. The Gene Expression Omnibus(GEO) and Human Protein Atlas 1 databases were analyzed to examine both the mRNA and protein expression of 14-3-3η in OP. Gene enrichment analyses were performed to explore the underlying mechanism of 14-3-3η based on DAVID. miRWalk was used to predict the associated miRNAs. The statistics were analysed by R software and SPSS software. 14-3-3η was overexpressed and knock down expressed in BMSCs by lentiviral vector transfecting. And BMSCs were induced by hypoxia. qRT-PCR and Western-Blot verified the expression of mRNA and protein. Scratch assay detected the migration of osteocytes. Co-immunoprecipitation and luciferase assay studied the 14-3-3η targeted protein and miRNA. overexpression and knock down of miRNA to verify the relationship of 14-3-3η and target genes. The 14-3-3η mRNA expression level was low in patients with osteoporosis, as corroborated by immunohistochemical staining images. Functional analyses revealed enrichment of the MAPK-associated cascade. 14-3-3η was correlated with MAPK family proteins and five key miRNAs, including mir-142-3p. In addition, 14-3-3η knockdown in BMSCs increased the mRNA and protein expression levels of Hif-α, VEGF, BMP-2, OPN, OST, and Runx2, and enhanced the cells migration ability. Under hypoxic conditions, Hif-α and BMP-2 protein expression levels were upregulated, whereas those of 14-3-3η and MAPK3 were downregulated. Co-immunoprecipitation experiments showed decreased binding of 14-3-3η to MAPK3. 14-3-3η knockdown produced the same results as hypoxia induction. Adding caspase3 inhibitor and knocking down 14-3-3η again prevented MAPK3 cleavage by caspase3 and inhibited BMP-2 expression. Moreover, under hypoxic conditions, miR-142-3P expression was upregulated and luciferase assays revealed 14-3-3η as its target gene. miR-142-3P overexpression decreased mRNA and protein levels of 14-3-3η and MAPK3, while increasing BMP-2 expression. miR-142-3P knockdown reversed these results. BMSC osteogenesis was suppressed by 14-3-3η, whereas miRNA-142-3p promoted it through the inhibition of 14-3-3η.

RIOK3 potentially regulates osteogenesis-related pathways in ankylosing spondylitis and the differentiation of bone marrow mesenchymal stem cells.

RNA-binding proteins (RBPs), which are key effectors of gene expression, play critical roles in inflammation and immune regulation. However, the potential biological function of RBPs in ankylosing spondylitis (AS) remains unclear. We identified differentially expressed genes (DEGs) in peripheral blood mononuclear cells (PBMCs) of five patients with AS and three healthy persons by RNA-seq, obtained differentially expressed RBPs by overlapping DEGs and RBPs summary table. RIOK3 was selected as a target RBP and knocked down in mouse bone marrow mesenchymal stem cells (mBMSCs), and transcriptomic studies of siRIOK3 mBMSCs were performed again using RNA-seq. Results showed that RIOK3 knockdown inhibited the expression of genes related to osteogenic differentiation, ribosome function, and ß-interferon pathways in mBMSCs. In vitro experiments have shown that RIOK3 knockdown reduced the osteogenic differentiation ability of mBMSCs. Collectively, RIOK3 may affect the differentiation of mBMSCs and participate in the pathogenesis of AS, especially pathological bone formation.

Silencing miR-181b-5p upregulates PIAS1 to repress oxidative stress and inflammatory response in rats with alcoholic fatty liver disease through inhibiting PRMT1.

OBJECTIVE: This study aimed to probe the function of microRNA-181b-5p (miR-181b-5p)/protein inhibitor of activated STAT1 (PIAS1)/protein arginine methyltransferase 1 (PRMT1) axis in the progression of alcoholic fatty liver disease (AFLD). METHODS: A rat model of AFLD was established and treated with altered miR-181b-5p, PIAS1 or PRMT1 expression constructs to identify their effects on liver function, serum inflammation, liver tissue oxidative stress, hepatocyte apoptosis and pathological changes of liver tissue in rats using a series of assays. miR-181b-5p, PIAS1 and PRMT1 levels were detected, and the targeting relationship between miR-181b-5p and PIAS1 was confirmed. RESULTS: MiR-181b-5p and PRMT1 were elevated while PIAS1 was reduced in AFLD rat liver tissues, miR-181b-5p inhibition, PIAS1 overexpression or PRMT1 inhibition improved liver function, attenuated inflammation, oxidative stress, pathological changes and hepatocyte apoptosis in AFLD rat liver tissues. The impacts of miR-181b-5p inhibition on AFLD rats were reversed by PIAS1 silencing. PIAS1 was confirmed as a target gene of miR-181b-5p, and miR-181b-5p regulated PRMT1 expression through binding to PIAS1. CONCLUSION: Inhibiting miR-181b-5p can promote the expression of PIAS1, thereby inhibiting PRMT1 and ultimately improving AFLD.

[Prediction of Prenatal Ultrasound Screening Staff's Situation in Beijing Based on ARIMA Model].

Objective To understand the current situation and predict the trends in number and composition of prenatal ultrasound screening staff in Beijing. Methods We analyzed the region,age,professional title and other characteristics of prenatal ultrasound screening personnel in Beijing during 2007-2015.We then built an ARIMA model basing on the current situation to predict the number and composition of the staff in 2016-2020. Results The number of prenatal ultrasound screening staff showed an upward trend in 2007-2020 and was predicted to reach 1269 in 2020.During this period,the educational achievement and professional title of the staff showed a downward trend,and the working years became shorter,mainly below 5 years.The proportion of resident doctors remained at 26.6%,and that of the staff receiving further education would reach 43.2% by the end of 2020. Conclusion The prediction under ARIMA model suggests that efforts should be made to strengthen the training of young doctors and provide them opportunities for further study.

Association study of the serum 25(OH)D concentration and myopia in Chinese children.

ABSTRACT: To analyze the serum 25 hydroxyvitamin D (25[OH]D) concentration in Chinese children with myopia and explore its correlation with myopia.From July to September in 2019, myopic children were collected from the Myopia Influencing Factors Survey Project. The basic information and vision related behaviors of the subjects were collected by questionnaire. The diopter of the children without dilated pupils was measured by the computerized refractometer. Meanwhile, 5 ml fasting venous blood samples were collected for the determination of serum 25(OH)D concentration.A total of 186 children were included in this study, including 90 males and 96 females, with an average age of 8 ±â€Š3.26 years. The detection rate of serum 25(OH)D deficiency in myopic children was 65.59% (122/186). There was statistical significance in the detection rate of serum 25(OH)D deficiency in children with different myopic degrees (χ2 = 6.635, P = .010). The average serum 25(OH)D concentration in myopic children was 14.86 (10.67-18.96) ng/ml, and the difference of serum 25(OH)D concentration in children with different myopia degrees was statistically significant (Z = 20.23, P < .001). Logistic regression analysis showed that after controlling for gender, parental myopia, after-school class, and outdoor activities, the prevalence of developing moderate and high myopia was 2.051 times (95% confidence interval: 1.272-3.724) higher in the serum 25(OH)D deficiency group than in the serum 25(OH)D sufficiency group. There is a positive correlation between serum 25(OH)D concentration and the equivalent spherical degree of myopic children.The study found that serum 25(OH)D concentration is closely related to the prevalence of myopia in Chinese children. The results further support the conclusion that children with a higher level of serum 25(OH)D have a lower prevalence of moderate to high myopia. The results of this study provide a basis for further research into the relationship between vitamin D and visual development in children and its mechanisms.

DL-3-n-butylphthalide ameliorates diabetes-associated cognitive decline by enhancing PI3K/Akt signaling and suppressing oxidative stress.

DL-3-n-Butylphthalide (DL-NBP), a small molecular compound extracted from the seeds of Apium graveolens Linn (Chinese celery), has been shown to exert neuroprotective effects due to its anti-inflammatory, anti-oxidative and anti-apoptotic activities. DL-NBP not only protects against ischemic cerebral injury, but also ameliorates vascular cognitive impairment in dementia patients including AD and PD. In the current study, we investigated whether and how DL-NBP exerted a neuroprotective effect against diabetes-associated cognitive decline (DACD) in db/db mice, a model of type-2 diabetes. db/db mice were orally administered DL-NBP (20, 60, 120 mg· kg-1· d-1) for 8 weeks. Then the mice were subjected to behavioral test, their brain tissue was collected for morphological and biochemical analyses. We showed that oral administration of DL-NBP significantly ameliorated the cognitive decline with improved learning and memory function in Morris water maze testing. Furthermore, DL-NBP administration attenuated diabetes-induced morphological alterations and increased neuronal survival and restored the levels of synaptic protein PSD95, synaptophysin and synapsin-1 as well as dendritic density in the hippocampus, especially at a dose of 60 mg/kg. Moreover, we revealed that DL-NBP administration suppressed oxidative stress by upregulating Nrf2/HO-1 signaling, and increased brain-derived neurotrophic factor (BDNF) expression by activating PI3K/Akt/CREB signaling in the hippocampus. These beneficial effects of DL-NBP were observed in high glucose-treated PC12 cells. Our results suggest that DL-NBP may be a potential pharmacologic agent for the treatment of DACD.

Association between low vision and sleep duration among primary and middle school students / 预防医学

Objective @#To understand the relationship between sleep duration and low vision among primary and middle school students, so as to provide the reference for promoting eye health of primary and middle school students.@* Methods @#Using stratified cluster sampling method, the students were selected from four primary schools, four junior high schools and three senior high schools in Dinghai, Putuo, Daishan and Shengsi of Zhoushan. The questionnaire for the influencing factors of myopia in the national monitoring and intervention project of common diseases and influencing factors among students in 2019 was used to collect their demography, video display terminal use, outdoor activity, parents'myopia and sleep duration. The multivariate logistic regression model was established to analyze the relationship between sleep duration and low vision among the students. @*Results @#A total of 3 016 questionnaires were sent out, and 2 932 valid ones were returned. The effective rate was 97.21%. There were 1 537 ( 52.42% ) males and 1 395 females ( 47.58% ); 947 ( 32.30% ) primary school students and 1 985 ( 67.70% ) middle school students; 2 328 ( 79.40% ) students with low vision. There were 1 022 ( 34.85% ), 903 (30.80%), 697 ( 23.77% ) and 310 ( 10.57% ) students with the daily sleep duration of <8 hours, 8-<9 hours, 9-<10 hours and ≥10 hours, respectively. The multivariate logistic regression analysis showed that the risk of low vision was lower when the daily sleep duration of students was 8-<9 hours ( OR=0.735, 95%CI: 0.561-0.963 ) and 9-<10 hours ( OR=0.605, 95%CI: 0.446-0.825 ). @*Conclusion @#Adequate sleep duration is conducive to reduce the risk of low vision among primary and middle school students.

Reliability and validity of the Chinese version of the new fear of hypoglycemia scale: FH-15.

OBJECTIVE: This study aimed to evaluate the reliability and validity of the Chinese version of the Fear of Hypoglycemia scale with 15 items (FH-15). METHODS: After obtaining the original author's authorization, the English version of the FH-15 scale was translated, back translated, and culturally debugged to obtain the Chinese version of FH-15. A convenient sampling method was used to extract patients with type 2 diabetes from four tertiary hospitals in Tianjin. A total of 408 patients with type 2 diabetes were investigated in the hospital to test the reliability and validity of Chinese version FH-15 scale. RESULTS: The content validity index of the scale was 0.92, and the content validity index of each item was 0.8-1.0. The exploratory factor analysis extracted three common factors (fear, avoidance, and interference), which contained 15 items, and the cumulative variance contribution rate was 71.245%. The confirmatory factor analysis results showed that the model fit was better at 1.981 χ 2/df, GFI = 0.901, CGI = 0.962, TLI = 0.952, and RMSEA = 0.070. The cut-off value for the total hypoglycemia fear scale was 30.5. The Cronbach's α coefficient of the three dimensions of the scale was 0.918, the Cronbach's α coefficient of each dimension is 0.876-0.916, the test-retest reliability was 0.903, and the test-retest reliability of each factor was 0.733-0.930. CONCLUSION: The Chinese version of the FH-15 scale can be considered reliable and valid. The item expression is concise, clear, and easy to understand. It is suitable for clinical practice as an initial screening tool to identify and evaluate the severity of fear of hypoglycemia in patients with type 2 diabetes.

Regeneration of islet ß-cells in tree shrews and rats.

BACKGROUD: Current understanding of injury and regeneration of islet ß-cells in diabetes is mainly based on rodent studies. The tree shrew is now generally accepted as being among the closest living relatives of primates, and has been widely used in animal experimentation. However, there are few reports on islet cell composition and regeneration of ß-cells in tree shrews. METHODS: In this study, we examined the changes in islet cell composition and regeneration of ß-cells after streptozotocin (STZ) treatment in tree shrews compared with Sprague-Dawley rats. Injury and regeneration of islet ß-cells were observed using hematoxylin and eosin (HE) staining and immunohistochemical staining for insulin, glucagon, somatostatin and PDX-1. RESULTS: Our data showed that in rats islet injury was most obvious on day 3 after injection, and islet morphologies were significantly restored by day 21. Regeneration of islet ß-cells was very pronounced in rats, and mainly involved regeneration of centro-acinar cells and transformation of extra-islet ductal cells. In tree shrews, the regeneration of islet ß-cells was not as significant. On days 3 and 7, only scattered regenerated cells were observed in the remaining islets. Further, no regeneration of centro-acinar cells was observed. CONCLUSION: The results suggest that the repair mechanism of islet ß-cells in tree shrews is similar to that of humans.

High-fat-diet-induced obesity upregulates the expression of lymphoid chemokines and promotes the formation of gastric lymphoid follicles after Helicobacter suis infection.

Helicobacter suis colonizes the stomachs of a variety of animals, including humans, and is more likely than other Helicobacter species to induce gastric mucosa-associated lymphoid tissue lymphoma. Obesity is a low-grade chronic inflammatory state in which the induction of a chemokine network contributes to a variety of diseases. However, the effect of obesity on the development of gastric MALT in the presence of H. suis infection remains unclear. Here, we reveal that high-fat-diet-induced obesity upregulates the expression of lymphoid chemokines in the stomach and accelerates the H. suis infection-induced formation of gastric lymphoid follicles, potentially via a mechanism that involves the activation of the nuclear factor kappa B (NF-κB) signaling pathway. These findings provide novel insight into the pathogenesis of obesity-related diseases, especially those induced by Helicobacter infection.

[Preparation of tranexamic acid-loaded porous starch and evaluation of its hemostatic ability].

This study was aimed to develop a new generation of ideal hemostatic powder which can be safely, effectively and easily used mainly to first aid anterior to hospital by the synergistic effect of physical and chemical hemostatic mechanisms. The tranexamic acid(TA)-loaded porous starch(PS) (TAPS) was prepared by using PS as carrier and TA as loaded drug component. The absorption property of TAPS was evaluated by water absorption; the hemostatic ability of TAPS was evaluated by test in vitro and in vivo, the blood coagulation time of TAPS was detected by using Lee-white method. The experiment was divided into 3 groups: blank control group, Yunnan Baiyao group and TAPS group, each group with 10 blood samples in vitro test; the 27 SD rats were used to test in vivo, and randomly were divided into 3 groups: PS,Yunnan Baiyao and TAPS, each group consisted of 9 rats for establishing the animal model of liver trauma and detecting the complete hemostasis time. The results showed that the water absorption of PS did not be affected by TA when dose of TA loaded in PS was <0.02 g/g PS. There was no statistic difference in blood coagulation time between TAPS and PS groups(P > 0.05). The complete hemostatic time of TAPS for trauma of left lobe liver was 236.67 ± 55.00 seconds, which was shorter than that of Yunnan Baiyao (340.00 ± 73.48 seconds) and PS (396.67 ± 68.37 seconds) (P < 0.05 and P < 0.01, respectively). It is concluded that PS can load TA and play the hemostatic effect through releasing TA; the TA loading <0.02 g/g PS did not affect the water absorption and pro-coagulation properties. The TA can enhance the hemostatic efficacy of PS, the hemostatic property of TAPS is derived from synergism of physical and chemical hemostatic mechanisms.

Inhalation of hydrogen gas reduces liver injury during major hepatotectomy in swine.

AIM: To study the effect of H2 gas on liver injury in massive hepatectomy using the intermittent Pringle maneuver in swine. METHODS: Male Bama pigs (n = 14) treated with ketamine hydrochloride and Sumianxin II as induction drugs followed by inhalation anesthesia with 2% isoflurane, underwent 70% hepatotectomy with loss of bleeding less than 50 mL, and with hepatic pedicle occlusion for 20 min, were divided into two groups: Hydrogen-group (n = 7), the pigs with inhalation of 2% hydrogen by the tracheal intubation during major hepatotectomy; contrast-group (n = 7), underwent 70% hepatotectomy without inhalation of hydrogen. Hemodynamic changes and plasma concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hyaluronic acid (HA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and malondialdehyde (MDA) in liver tissue were measured at pre-operation, post-hepatotectomy (PH) 1 h and 3 h. The apoptosis and proliferating cell nuclear antigen (PCNA) expression in liver remnant were evaluated at PH 3 h. Then we compared the two groups by these marks to evaluate the effect of the hydrogen in the liver injury during major hepatotectomy with the Pringle Maneuver in the swine. RESULTS: There were no significant differences in body weight, blood loss and removal liver weight between the two groups. There was no significant difference in changes of portal vein pressure between two groups at pre-operation, PH 30 min, but in hydrogen gas treated-group it slightly decrease and lower than its in contrast-group at PH 3 h, although there were no significant difference (P = 0.655). ALT and AST in Hydrogen-group was significantly lower comparing to contrast-group (P = 0.036, P = 0.011, vs. P = 0.032, P = 0.013) at PH 1 h and 3 h, although the two groups all increased. The MDA level increased between the two group at PH 1 h and 3 h. In the hydrogen gas treated-group, the MDA level was not significantly significant at pre-operation and significantly low at PH 1 h and 3 h comparing to Contrast-group (P = 0.0005, P = 0.0004). In Hydrogen-group, the HA level was also significantly low to contrast-group (P = 0.0005, P = 0.0005) although the two groups all increased at PH 1 h and 3 h. The expression of cluster of differentiation molecule 31 molecules Hydrogen-group was low to Contrast-group. However, PCNA index (%) was not statistically significant between the two groups (P = 0.802). Microphotometric evaluation of apoptotic index (AI) in terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-stained tissue after hepatotectomy for 3h, the AI% level in the hydrogen was significantly low to contrast-group (P = 0.012). There were no significant difference between Hydrogen-group and contrast-group at pre-operation (P = 0.653, P = 0.423), but after massive hepatotectomy, the TNF-α and IL-6 levels increase, and its in Hydrogen-group was significantly low compared with contrast-group (P = 0.022, P = 0.013, vs. P = 0.016, P = 0.012), respectively. Hydrogen-gas inhalation reduce levels of these markers and relieved morphological liver injury and apoptosis. CONCLUSION: H2 gas attenuates markedly ischemia and portal hyperperfusion injury in pigs with massive hepatotectomy, possibly by the reduction of inflammation and oxidative stress, maybe a potential agent for treatment in clinic.

The susceptibility of three strains of Chinese minipigs to diet-induced type 2 diabetes mellitus.

Researchers have extensively used animal models to study diabetes mellitus. In this study, the authors determined the susceptibility of three strains of Chinese minipigs to diet-induced type 2 diabetes mellitus. For 8 months, the researchers fed Nongda control minipigs (n=4) a normal diet and fed Bama, Wuzhishan and Nongda minipigs (n=6 per group) a high-sucrose, high-fat diet. They measured the minipigs' body weights, fasting serum glucose concentrations and insulin concentrations each month. Every 2 months, they measured serum triglyceride, cholesterol, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels and carried out intravenous glucose tolerance tests (IVGTTs). The Bama and Wuzhishan minipigs were relatively susceptible to diabetes induced by the high-sucrose, high-fat diet, though susceptibility differed among individual animals in the same strain. On the other hand, Nongda minipigs were relatively resistant to diet-induced diabetes. These results provide a foundation for diabetes-related genetic analyses in minipigs with high and low susceptibility to diet-induced type 2 diabetes.

[Pharmacodynamic tests of wulong kangai on transplantable tumors in mice].

OBJECTIVE: To observe the pharmacodynamic and side effects of Wulong Kangai, a new drug of Chinese traditional herbal medicine, on 4 strains of mice transplantable tumors. METHOD: Mice transplantable tumors S180, H22, P388 and Lewis were used in the pharmacodynamic test on the granules of Wulong Kangai. The test on each tumor strain was repeated three times. In each test, 50 mice were used and divided into 5 groups. They were negative control group treated by physiological saline, cyclophosphamide control group and 3 test groups treated respectively with Wulong Kangai at deferent dosages of 10, 25, 40 g x kg(-1) x d(-1) in the treatment of Lewis and P388 and 15, 30, 50 g x kg(-1) x d(-1) in the treatment of S180 and H22. RESULT: The tumor weight were inhibited at the rates of 90.1%, 30.8%, 49.8% and 52. 3% in the mice with tumors of Lewis, P388, S180, and H22 by high dosage of Wulong Kangai as compared with negative control group. The inhibitory rates in cyclophosphamide groups were 90.6%, 77.2%, 79.6% and 60.3% respectively. The mice body weights grew slower in high dose groups treated by Wulong Kangai granule. CONCLUSION: Wulong Kangai was effective in treating mice transplantable tumors of Lewis, P388, S180 and H22 with a dose-dependent manner. The Lewis was the most sensitive strain to the drug among the 4 kinds of tested tumors. Side effects appeared during 9-11 days of uninterrupted treatment with high dose Wulong Kangai.