[Applications of stem cell-derived extracellular vesicles in bone regenerative therapy].

Stem cell-derived exosomes and microvesicles are nanoscale extracellular vesicles which have merged as mediators of intercellular communication through delivering bioactive substances. They have showed promising potential in regenerative therapy due to their capacity in promoting tissue regeneration. It has been reported that stem cell-derived extracellular vesicles could enhance bone regeneration. The underlying mechanisms included inhibiting osteocyte apoptosis induced by ischemia and hypoxia, enhancing the proliferation, migration, and osteogenic differentiation of stem cells, and promoting angiogenesis. Further investigations indicated that microRNA seemed to play an important role in exosome-mediated regeneration. In this review, we summarized the biogenesis, components and functions of stem cell-derived extracellular vesicles as well as the current progress of their mechanisms and applications in bone regeneration.

[Correlation study of IL-18 expression in HBsAg positive parturients in intrauterine transmission of HBV].

Objective: To investigate the expression of IL-18 in peripheral blood of HBsAg positive parturients in intrauterine transmission of HBV. Methods: A case-control study was conducted in 282 HBsAg positive parturients and 43 health parturients (control group) in Northwest Women and Children Hospital of Shaanxi Province. Enzyme-linked immunosorbent assay (ELISA) was used to detect five serological makers of hepatitis B, real time PCR was used to detect HBV DNA, and flow liquid chip method was used to detect IL-18 levels in peripheral blood of parturients and newborns. Results: The incidence of dominant HBV infection (DBI), occult HBV infection (OBI) and intrauterine transmission of HBV were 8.42% (24/285), 40.00% (114/285) and 48.42% (138/285), respectively. The level of IL-18 in peripheral blood of HBsAg-negative parturients were significantly lower than those of HBsAg-positive parturients (P=0.001), non-HBV intrauterine transmission (NBIT) group (P=0.001) and OBI group (P<0.001). The level of IL-18 in HBeAg negative group was significantly lower than that in HBeAg positive group (P=0.023). When HBV DNA load was ≥10(3) copies/ml, the level of IL-18 was significantly higher than that in HBsAg-negative group (P<0.01). With the increase of HBV DNA load in maternal blood, the level of IL-18 increased (P=0.024). When HBV DNA load was 10(3)-10(6) copies/ml, the level of IL-18 in DBI group was significantly lower than that in NBIT group (P=0.022), and increased with the increase of HBV DNA load in maternal blood (P=0.016). With the increased severity of intrauterine transmission of HBV, the level of IL-18 in non-hepatitis B vaccine group decreased significantly (P=0.044). The level of IL-18 in non-hepatitis B vaccine group and immunoglobulin injection group was significantly higher than that in NBIT group (P<0.05). Multivariate analysis showed that the linear relationship between maternal HBeAg status and maternal IL-18 levels had statistical significance (P=0.01). Conclusions: IL-18 is a higher level balance regulator of Th1/Th2 immune network. Monitoring the level of IL-18 in HBsAg-positive parturients can be used not only for predicting the probability of DBI and OBI, but also as an intervention mean, especially for those who are HBeAg-positive and had HBV DNA load ≥10(3) copies/ml, to improve maternal cellular immune function, which is conducive to interrupting intrauterine transmission and providing a theoretical basis for the prevention and control of HBV intrauterine transmission.

[Role of TLR 9 expression in maternal peripheral blood and placenta in intrauterine transmission of HBV].

Objective: To explore the role of TLR 9 in intrauterine transmission of hepatitis B virus (HBV) through blood pathway and placenta. Methods: Epidemiological investigation was carried out in 290 HBsAg positive parturients and 45 normal parturients (control group) in Northwest Women and Children Hospital of Shaanxi Province. Enzyme-linked immunosorbent assay (ELISA) was used to detect five serological makers of hepatitis B and TLR 9 levels in peripheral blood of pregnant women and newborns. HBV DNA was detected by real-time fluorescence quantitative PCR. Detection of TLR 9 expression in placenta by immunohistochemical method. A case-control study was conducted to analyze the difference of TLR 9 levels in placenta and peripheral blood of HBsAg- positive pregnant women with intrauterine transmission of HBV. Results: The incidence of dominant HBV infection (DBI), occult HBV infection (OBI) and intrauterine transmission of HBV were 9.28% (27/291), 40.21% (117/291) and 49.48% (144/291) respectively. (1) The level of TLR 9 in peripheral blood of HBsAg-positive parturients, non-HBV intrauterine transmission (NBIT) group and OBI group were significantly lower than that of control group (P<0.001). The level of TLR 9 in DBI group was significantly higher than those in NBIT group and OBI group (P=0.000). (2) The TLR 9 level in HBeAg-negative group was significantly lower than that in HBeAg-positive parturients in OBI group (P=0.01). (3) With the increased severity of intrauterine transmission of HBV in each HBV DNA load group, the TLR 9 level in maternal peripheral blood increased significantly (P<0.05). (4) With the increased severity of intrauterine transmission of HBV, the levels of TLR 9 increased significantly in antiviral therapy, immunoglobulin injection and non-hepatitis B vaccine groups (P<0.05). (5) The expression of TLR 9 in placenta tissues with DBI group was significantly higher than that in OBI group and NBIT group (P<0.05). Conclusions: HBV can inhibit the secretion of TLR 9 in parturient to some extent, but HBeAg can stimulate the secretion of TLR 9. However, with the increased severity of intrauterine transmission of HBV, the level of TLR 9 in parturients is increased by intra-group cross-differentiation. Therefore, TLR 9 is not an independent marker for screening and grouping, but it can be used as an reference indicator for the monitoring and management of HBsAg-positive parturients.

[Effect of IFN-γ and IL-12 expressions on intrauterine transmission in HBsAg-positive parturientsin late pregnancy].

Objective: To investigate the influence of IFN-γ and IL-12 levels in prenatal peripheral blood of HBsAg-positive parturients on intrauterine transmission of hepatitis B virus (HBV). Methods: A case-control study was conducted in 282 HBsAg positive parturients and 43 health parturients (control group) in Northwest Women and Children Hospital of Shaanxi Province. Enzyme-linked immunosorbent assay (ELISA) was used to detect five serological makers of hepatitis B in peripheral blood of parturients. HBV DNA was detected by real-time fluorescence quantitative PCR. Detection of cytokines IFN-γ and IL-12 levels were conducted with liquid chip-based flow cytometry method. The serum levels of five serological markers of hepatitis B and HBV DNA in 285 newborns were detected within 24 hours after birth. Results: The incidence of intrauterine dominant infection (DBI), occult infection (OBI) and intrauterine transmission of HBV in HBsAg positive parturients were 7.37% (21/285), 40.70% (116/285) and 48.07% (137/285), respectively. The level of IFN-γ in peripheral blood of HBsAg-negative parturients was significantly lower than those of HBsAg-positive parturients (t=-2.55, P=0.011), NBIT group (t=-2.54, P=0.012) and OBI group (t=-2.33, P=0.021). In HBV DNA load of 10(3)-10(6) copies/ml group, the levels of IFN-γ in the DBI group were significantly lower than those in OBI group and NBIT group (P<0.01). The level of IFN-γ in maternal peripheral blood decreased significantly with the increased severity of intrauterine transmission of HBV (χ(2)=6.40, P=0.041). In the antiviral treatment group, the level of IL-12 in maternal peripheral blood decreased significantly with the increased severity of intrauterine transmission of HBV (χ(2)=8.90, P=0.012). Multivariate analysis showed that there was a significant linear relationship between maternal IFN-γ level and maternal age, placenta previa and hepatitis B vaccine injection (P<0.05). The linear relationship between the level of maternal IL-12 and the mode of rupture and hepatitis B vaccine injection had statistical significance (P<0.05). Conclusions: HBV can stimulate the expression of IFN-γ and inhibit the secretion of IL-12 in pregnant and lying-in women, but the expression of IFN-γ in HBsAg-positive parturients showed intra-group differentiation, and the maternal level of IFN-γ will decrease in HBeAg-positive and high-HBV DNA loadstatus. Increasing the levels of IFN-γ and IL-12 in HBsAg-positive parturients is beneficial to block intrauterine transmission of HBV, especially DBI.

[Disease burden of influenza in schools and child care settings in rural areas of Hangzhou, 2016-2018].

Objective: The objective of this study was to analyze the disease burden of influenza in schools and child care settings in rural areas of Hangzhou. Methods: Hospital visit influenza cases aged 3-17 years in hospitals that reported based on influenza surveillance system from 2016 to 2018 in Chun'an county, Hangzhou city were selected as study subjects and a total of 294 confirmed cases of influenza were selected using system sampling method. Questionnaires were designed to investigate the basic information and data on inpatients and outpatients among, health care and life quality, etc.. Direct and indirect economic burden and disability adjusted life year (DALY) were analyzed and compared among different age groups. Results: The mean age of investigated subjects was (8.88±3.92) years. A total of 143 (48.64%) investigated cases were male. In total of 283 (96.26%) cases were outpatients. The total economic burden was 124 743.95 CNY. The mean economic burden was 424.30 CNY per person. The mean direct and indirect economic burden was 361.33 and 62.97 CNY per person respectively. The difference of the mean direct, indirect and total economic burden per person between different age group was statistically significant (P<0.001). The 3-5 years age group showed the highest economic burden with the median value of direct, indirect and total economic burden per person being 276.24, 50.98 and 321.26 CNY, respectively, while the 12-17 years age group showed the lowest values with 175.30, 26.54, 201.79 CNY, respectively. The DALY of 294 influenza cases was 1.18, and the median of burden strength was 3.21 DALY/thousand. The difference of the burden of strength between different age group influenza case was statistically significant (P<0.001), of which the 12-17 years age group showed the highest value with 4.25 DALYs/thousand while the 3-5 years age group showed the lowest value with 2.60 DALY/thousand. Conclusion: The disease burden of influenza was heavy in schools and kindergartens in rural areas of Hangzhou city, with the cases aged from 3 to 5 years showing higher economic burden and cases aged from 12 to 17 years showing greater burden strength.

The apoptosis in arsenic-induced oxidative stress is associated with autophagy in the testis tissues of chicken.

The aim of this study is to investigate whether arsenic (As) could induce testicular poisoning and influence the oxidative stress, apoptosis and autophagy in chickens. Seventy-two 1-day-old male Hy-line chickens were divided into 4 groups which were exposed to 0, 0.625, 1.25, and 2.5 mg/kg body weight (BW) of arsenic trioxide (As2O3) for 30, 60 and 90 days, respectively. Histological and ultrastructural changes, antioxidant enzyme activity, mRNA and protein levels of apoptosis and autophagy-related genes were detected. Oxidative stress injuries were obvious in the testes exposure to As2O3, which resulted in the decreased activities of antioxidant enzymes, such as catalase (CAT) and superoxide dismutases (SOD). Meanwhile, the changes of mRNA and protein levels of apoptosis and autophagy-related genes showed that As2O3 exposure induced enhanced testicular apoptosis and increased the levels of autophagy markers such as Microtubule associated protein light chains 3-II (LC3-II), dynein, Beclin-1, Autophagy associated gene 5 (ATG5) and ATG4B but not LC3-I and mammalian target of rapamycin (mTOR), and demonstrated the cross-talk between apoptosis and autophagy. Histological and ultrastructural abnormalities confirm the changes of the above indicators. Taken together, our findings provide deeper insights into roles of excessive apoptosis and autophagy in the aggravation of testicular damage, which could contribute to a better understanding of As2O3-induced testicular poisoning in chickens.