One pot preparation of muti-mode nanoplatform to combat ovarian cancer.

Ovarian cancer is one of the most common gynecological cancers with high mortality rate. The battle against ovarian cancer usually impaired by the evolved multidrug resistance (MDR) phenotype as well as metastasis in cancers, which urgently call for the development of multi-mode strategies to overcome the MDR and reduce metastasis. Considering the good benefits of ferroptosis and photothermal therapy (PTT) in cancer management, we herein proposed a facile way to construct nanoparticle platform (Fe-Dox/PVP) composed of ferric chloride, doxorubicin (Dox) and polyvinyl pyrrolidone (PVP) for the multi-mode therapy of ovarian cancer using chemotherapy, ferroptosis and mild hypothermia PTT. Our results demonstrated that Fe-Dox/PVP with mild hypothermia was shown to have improved endosomal escape/drug delivery, enhanced ferroptosis induction and good tumor targeting effects. Most importantly, the integration of all three effects into one platform provided increased anti-metastasis effect and promising in vitro/in vivo anticancer performance with high biocompatibility. In this study, we offer a facile and robust way to prepare a multi-mode nanoplatform to combat ovarian cancer, which can be further extended for the management of many other cancers.

Loss of p16 does not protect against premature ovarian insufficiency caused by alkylating agents.

BACKGROUND: Chemical agents such as alkylating agents (AAs) that are commonly used for the treatment of cancer cause great damage to the ovaries, thereby significantly increasing the risk of premature ovarian insufficiency (POI). However, the exact molecules underlying AA-induced POI remain largely obscure. Upregulation of the p16 gene may contribute to the progression of POI. As yet, no in vivo data from p16-deficient (KO) mice are available to demonstrate a critical role of p16 in POI. In the present study, we employed p16 KO mice to investigate whether loss of p16 could protect against POI caused by AAs. METHODS: WT mice and their p16 KO littermates received a single dose of BUL + CTX to establish an AA-induced POI mouse model. One month later, oestrous cycles were monitored. Three months later, some of the mice were sacrificed to collect sera for measurements of hormone levels and ovaries for measurements of follicle counts, the proliferation and apoptosis of granulosa cells, ovarian stromal fibrosis and vessels. The remaining mice were mated with fertile males for the fertility test. RESULTS: Our results showed that treatment with BUL + CTX significantly disrupted the oestrous cycles, increased the levels of FSH and LH while decreasing the levels of E2 and AMH, decreased the counts of primordial follicles and growing follicles while increasing the counts of atretic follicles, reduced the vascularized area in the ovarian stroma, and decreased fertility. All of these results were comparable between WT and p16 KO mice treated with BUL + CTX. In addition, ovarian fibrosis was not increased significantly in WT and p16 KO mice treated with BUL + CTX. Growing follicles with normal appearance had normally proliferating granulosa cells (without apparent apoptosis). CONCLUSION: We concluded that genetic ablation of the p16 gene did not attenuate ovarian damage or help preserve the fertility of mice challenged by AAs. This study demonstrated for the first time that p16 is dispensable for AA-induced POI. Our preliminary findings suggest that targeting p16 alone may not preserve the ovarian reserve and fertility of females treated with AAs.

Analysis of the split insemination (IVF+ICSI) treatment in patients with borderline semen in first cycle.

PURPOSE: The aim of this study was to verify the effectiveness of the split insemination (IVF+ICSI) in patients with borderline semen for the first cycle, we furthermore compared the treatment outcome of the conventional IVF and ICSI on sibling oocytes with the rate of blastocyst formation in different days (day 5 or day 6) as primary outcome and pregnancy as secondary outcome to provide theoretical support for embryo selection. METHODS: Between January 2017 and November 2021,190 couples undergoing the split insemination (IVF+ICSI) cycle were enrolled in the study with at least eight oocytes and the borderline semen in first cycle to analyze the basic characteristics and clinical outcome. The remaining 157 patients were analyzed in this study to compare the IVF and ICSI after excluding those who were completely unfertilized by IVF (n=33) including a patient who was completely unfertilized by IVF and ICSI. RESULTS: Present study showed that about 32(32/190,16.8%) patients with borderline semen in first cycle were completely unfertilized performing the conventional IVF and only 1(1/190,0.53%) patient was completely unfertilized using the IVF and ICSI in the split insemination (IVF+ICSI), the rate of total fertilization failure (TFF) was significantly decrease by the ICSI treatment (16.8%&0.53%,P<0.0001). By the split oocytes, the fertilization rate was significantly superior in ICSI(729/982,74.2%) compared to IVF (486/940, 51.7%, P<0.0001), the usable blastocyst and high-quality blastocyst rate on the fifth day were statistically superior in IVF compared to ICSI(31.3% &22.8%,P=0.009) (27.3%&20.6%,P=0.03), The pregnancy rate, implantation rate and live birth rate in the IVF first cycle were higher than the ICSI(75.9%&64%, respectively) (52.3%&41.8%, respectively)(64.8%&54.7%, respectively),although there was no statistical difference,it is also about ten percentage points difference. CONCLUSIONS: The treatment of sibling oocyte with both IVF and ICSI could be an appropriate choice to prevent TFF and preserve the embryo development potential for the patients with the borderline semen in present study. Furthermore, the embryo development potential from conventional IVF was better than the embryo from the ICSI technology, the ICSI technology may have a negative effect on the embryo development.

BMI1 promotes spermatogonial stem cell maintenance by epigenetically repressing Wnt10b/ß-catenin signaling.

The self-renewal of spermatogonial stem cells (SSCs) requires a special microenvironment and is strictly controlled. Previously, we identified BMI1 as a key regulator of spermatogenesis in a knock-out mouse model. However, the mechanisms by which BMI1 regulates SSC maintenance remain largely unknown. Herein, we show that BMI1 is essential for SSC maintenance. BMI1 directs the transcriptional repression of target genes by increasing H2AK119ub and reducing H3K4me3 in SSCs. Furthermore, BMI1 inhibition resulted in the transcriptional activation of Wnt10b and thereby promoted the nuclear translocation of ß-catenin in SSCs. Importantly, the suppression of Wnt/ß-catenin signaling restored both the cytoplasmic expression of ß-catenin and SSC maintenance in BMI1-deficient SSCs. Finally, we demonstrated that Wnt/ß-catenin signaling was also involved in BMI1-mediated SSC maintenance in vivo. Altogether, our study not only reveals a novel mechanism for BMI1 in the process of SSC maintenance, but also provides a potential new strategy for treating male infertility.

PQQ Dietary Supplementation Prevents Alkylating Agent-Induced Ovarian Dysfunction in Mice.

Alkylating agents (AAs) that are commonly used for cancer therapy cause great damage to the ovary. Pyrroloquinoline-quinine (PQQ), which was initially identified as a redox cofactor for bacterial dehydrogenases, has been demonstrated to benefit the fertility of females. The aim of this study was to investigate whether PQQ dietary supplementation plays a protective role against alkylating agent-induced ovarian dysfunction. A single dose of busulphan (20 mg/kg) and cyclophosphamide (CTX, 120 mg/kg) were used to establish a mouse model of ovarian dysfunction. Feed containing PQQNa2 (5 mg/kg) was provided starting 1 week before the establishment of the mouse model until the date of sacrifice. One month later, estrous cycle period of mice were examined and recorded for consecutive 30 days. Three months later, some mice were mated with fertile male mice for fertility test. The remaining mice were sacrificed to collect serum samples and ovaries. One day before sacrifice, some mice received a single injection of BrdU to label proliferating cells. Serum samples were used for test hormonal levels. Ovaries were weighted and used to detect follicle counts, cell proliferation, cell apoptosis and cell senescence. In addition, the levels of inflammation, oxidative damage and Pgc1α expression were detected in ovaries. Results showed that PQQ treatment increased the ovarian weight and size, partially normalized the disrupted estrous cycle period and prevented the loss of follicles of mice treated with AAs. More importantly, we found that PQQ treatment significantly increased the pregnancy rate and litter size per delivery of mice treated with AAs. The protective effects of PQQ appeared to be directly mediated by promoting cell proliferation of granulosa, and inhibiting cell apoptosis of granulosa and cell senescence of ovarian stromal cells. The underlying mechanisms may attribute to the anti-oxidative stress, anti-inflammation and pro-mitochondria biogenesis effects of PQQ.Our study highlights the therapeutic potential of PQQ against ovarian dysfunction caused by alkylating agents.

BMI1 promotes spermatogonia proliferation through epigenetic repression of Ptprm.

Spermatogonia are accountable for spermatogenesis and male fertility, but the underlying mechanisms involved in spermatogonia maintenance are not clear. B lymphoma Mo-MLV insertion region 1 (BMI1) is a key component of epigenetic silencers. BMI1 is essential for stem-cell maintenance. Here, we attempted to uncover the role of BMI1 in spermatogonia maintenance using a mouse spermatogonia cell line (GC-1) and Bmi1-knockout (KO) mouse model. We showed that BMI1 promoted the proliferation and inhibited apoptosis of GC-1 cells. Mechanistically, we present in vitro and in vivo evidence to show that BMI1 binds to the promoter region of the Protein tyrosine phosphatase receptor type M (PTPRM) gene, thereby driving chromatin remodeling and gene silencing. Knockdown of Ptprm expression significantly improved spermatogonia proliferation in BMI1-deficient GC-1 cells. Collectively, our data show, for the first time, an epigenetic mechanism involving in BMI1-mediated gene silencing in spermatogonia maintenance, and provide potential targets for the treatment of male infertility.

Utilisation of community care services and self-rated health among elderly population in China: a survey-based analysis with propensity score matching method.

BACKGROUND: Elderly care and elderly health are the enormous challenges in such an aging society as China. Community care services have been developing rapidly in recent years in China as an increasingly mainstream care resource to promote elderly health. The purpose of this study is to examine the association between using community care services and self-rated health among Chinese elderly. METHODS: A cross-sectional survey was conducted in 2019 and 612 elderly people from China's Shaanxi province were enrolled. The binary logistic regression was first employed to explore the association between community care services utilisation and elderly health. Given the potential selection bias issue, the propensity score matching method was hired to generate comparable samples between participants who used these services and participants who didn't, and further examine the health benefits of using four types of services. RESULTS: The results of the binary logistic regression showed that the use of community care services predicted a better health status of elderly individuals. Overall, the results of the propensity score matching method showed the similar results. Specifically, with the nearest neighbors matching algorithm, using daily care services was significantly associated with a 0.246 increase in the self-rated health of the elderly (T = 1.83). For medical care services, the mean of self-rated health of elderly individuals who used these services was 3.542, significantly higher than those who didn't (T = 2.15). For spiritual comfort services, elderly individuals using these services showed a significant increase by 0.280 in the self-rated health (T = 1.82). For social and recreational services, the result of the nearest neighbor matching method was not statistically significant, while the results of kernel matching method and the mahalanobis matching method showed a significant increase in the self-rated health among elderly individuals using these services (T = 2.03, T = 2.03, respectively). All the estimated results passed the Rosenbaum bounds analysis and were not sensitive to hidden bias. CONCLUSIONS: Using community care services improved the self-rated health of the elderly. More effective measures may be implemented to increase access to care resources for senior citizens, and further improve their health status.

BMI1 Drives Steroidogenesis Through Epigenetically Repressing the p38 MAPK Pathway.

Testosterone biosynthesis progressively decreases in aging males primarily as a result of functional changes to Leydig cells. Despite this, the mechanisms underlying steroidogenesis remain largely unclear. Using gene knock-out approaches, we and others have recently identified Bmi1 as an anti-aging gene. Herein, we investigate the role of BMI1 in steroidogenesis using mouse MLTC-1 and primary Leydig cells. We show that BMI1 can positively regulate testosterone production. Mechanistically, in addition to its known role in antioxidant activity, we also report that p38 mitogen-activated protein kinase (MAPK) signaling is activated, and testosterone levels reduced, in BMI1-deficient cells; however, the silencing of the p38 MAPK pathway restores testosterone production. Furthermore, we reveal that BMI1 directly binds to the promoter region of Map3k3, an upstream activator of p38, thereby modulating its chromatin status and repressing its expression. Consequently, this results in the inhibition of the p38 MAPK pathway and the promotion of steroidogenesis. Our study uncovered a novel epigenetic mechanism in steroidogenesis involving BMI1-mediated gene silencing and provides potential therapeutic targets for the treatment of hypogonadism.

Bmi1 regulate tooth and mandible development by inhibiting p16 signal pathway.

To determine whether the deletion of p16 can correct tooth and mandible growth retardation caused by Bmi1 deficiency, we compared the tooth and mandible phenotypes of homozygous p16-deficient (p16-/- ) mice, homozygous Bmi1-deficient (Bmi1-/- ) mice, double homozygous Bmi1 and p16-deficient (Bmi1-/- p16-/- ) mice to those of their wild-type littermates at 4 weeks of age by radiograph, histochemistry and immunohistochemistry. Results showed that compared to Bmi1-/- mice, the dental mineral density, dental volume and dentin sialoprotein immunopositive areas were increased, whereas the ratio of the predentin area to total dentin area and that of biglycan immunopositive area to dentin area were decreased in Bmi1-/- p16-/- mice. These results indicate that the deletion of p16 can improve tooth development in Bmi1 knockout mice. Compared to Bmi1-/- mice, the mandible mineral density, cortical thickness, alveolar bone volume, osteoblast number and activity, alkaline phosphatase positive area were all increased significantly in Bmi1-/- p16-/- mice. These results indicate that the deletion of p16 can improve mandible growth in Bmi1 knockout mice. Furthermore, the protein expression levels of cyclin D, CDK4 and p53 were increased significantly in p16-/- mice compared with those from wild-type mice; the protein expression levels of cyclin D and CDK4 were decreased significantly, whereas those of p27 and p53 were increased significantly in Bmi1-/- mice; these parameters were partly rescued in Bmi1-/- p16-/- mice compared with those from Bmi1-/- mice. Therefore, our results indicate that Bmi1 plays roles in regulating tooth and mandible development by inhibiting p16 signal pathway which initiated entry into cell cycle.

Impact of Economic Accessibility on Realized Utilization of Home-Based Healthcare Services for the Older Adults in China.

Home-based healthcare service has gradually become the most important model to cope with aging in China. However, the contradiction between oversupply and insufficient demand of healthcare services is becoming increasingly serious. How to effectively improve the realized utilization of healthcare resources has become a key issue in the development of healthcare services. Based on the social background of "getting old before getting rich", this article explores the relationship between economic accessibility and realized utilization, and finds that the impact of economic accessibility on realized utilization is inverted U-shaped, not a linear positive effect. In addition, considering the moderating role of family support, it is found that family support can strengthen the inverted U-shaped effect of economic accessibility on realized utilization. Therefore, exerting the role of family and improving economic accessibility can effectively solve the dilemma of low utilization of healthcare services.

Rural-urban and gender differences in the association between community care services and elderly individuals' mental health: a case from Shaanxi Province, China.

BACKGROUND: While community care services have been developing rapidly as a new way to meet the growing demands of elderly individuals in China, their health benefits are virtually unknown. Thus, the aim of this study was to examine the Chinese elderly individuals' utilisation of community care services and its association with the mental health with comparing rural-urban and gender differences. METHODS: For this 2019 cross-sectional study, 687 elderly people from 7 counties (districts) of China's Shaanxi province were enrolled. Respondents' mental health level was assessed using a self-reported mental health measure. Four categories of community care services utilisation were examined: daily care services, medical care services, social and recreational services and spiritual comfort services. The binary logistic regression model was used in examining the association between community care services utilisation and mental health. RESULTS: Our results showed that there was a noted difference in mental health level between the male and female groups. Utilisation of medical care services and social and recreational services was significantly higher in the rural group than that in the urban group. Regression analysis showed that utilisation of daily care services (ß = 0.809, p = 0.008) and social and recreational service (ß = 0.526, p = 0.035) was significantly and positively associated with elderly individuals' mental health level. Specifically, daily care services utilisation predicted a better mental health of the rural elderly (ß = 1.051, p = 0.036) and the male elderly (ß = 1.133, p = 0.053), while social and recreational services utilisation predicted a better mental health of the urban elderly (ß = 0.927, p = 0.008) and the female elderly (ß = 0.864, p = 0.007). CONCLUSIONS: Our findings indicated varied levels of community care services utilisation and mental health are common among the elderly people in China. Community care services utilisation has a positive, albeit selective, association with elderly individuals' mental health. Further policies should strengthen the equitable development of high-quality community care services in urban and rural areas to improve the mental health of elderly individuals, and focus more on gender differences in terms of community care services needs.

Analysis of Biochemical and Clinical Pregnancy Loss Between Frozen-Thawed Embryo Transfer of Blastocysts and Day 3 Cleavage Embryos in Young Women: A Comprehensive Comparison.

Background: To determine whether the embryo developmental stage affects biochemical or clinical pregnancy loss in young women undergoing frozen-thawed embryo transfer (FET) and to investigate the underlying mechanism. Methods: This was a retrospective study including a total of 18,34 ß-HCG (human chorionic gonadotropin)-positive FET cycles. According to the morphological appearance (MA) of transferred blastocysts, FET cycles with blastocysts were divided into two groups: Group A: morphologically good (MG) blastocysts only, and Group B: at least one morphologically non-good (MNG) blastocyst. FET cycles with day 3 cleavage embryos were assigned as Group C. Biochemical and clinical pregnancy loss were the main outcome measures. Results: We predicted 78% in vivo-formed MG and 53.9% in vivo-formed day 5 blastocysts in Group C. (a) Including cases in Group A and Group B for binary logistic regression, we showed that Group B and day 6 blastocysts had significantly higher rates of BPL and CPL than Group A and day 5 blastocysts, respectively. (b) Including cases in Group A, Group B, and Group C for binary logistic regression, we showed that Group C had a significantly higher rate of BPL than Group A and day 5 blastocysts and a similar rate of BPL as Group B and day 6 blastocysts. Group C had a higher rate of CPL than Group A (p=0.071) and day 5 blastocysts (p=0.039), and a lower rate of CPL than Group B (p=0.199) and day 6 blastocysts (p=0.234). Conclusions: (1) MA and days of usable blastocysts could serve as independent factors affecting the occurrence of BPL and CPL. (2) Transfer of day 3 cleavage embryos may produce "unusable blastocysts" in vivo, which significantly increased the rate of BPL. (3) The rate of CPL resulting from the transfer of day 3 embryos may depend on the rate of in vivo-formed MG or day 5 blastocysts. Our study indicated that the difference in the BPL or CPL between transfer of blastocysts and day 3 cleavage embryos may largely depend on the quality of embryos transferred.

AMH has no role in predicting oocyte quality in women with advanced age undergoing IVF/ICSI cycles.

It has been widely acknowledged that anti-Müllerian hormone (AMH) is a golden marker of ovarian reserve. Declined ovarian reserve (DOR), based on experience from reproductive-aged women, refers to both the quantitative and qualitative reduction in oocytes. This view is challenged by a recent study clearly showing that the quality of oocytes is similar in young women undergoing IVF cycles irrespective of the level of AMH. However, it remains elusive whether AMH indicates oocyte quality in women with advanced age (WAA). The aim of this study was to investigate this issue. In the present study, we retrospectively analysed the data generated from a total of 492 IVF/ICSI cycles (from January 2017 to July 2020), and these IVF/ICSI cycles contributed 292 embryo transfer (ET) cycles (from June 2017 to September 2019, data of day 3 ET were included for analysis) in our reproductive centre. Based on the level of AMH, all patients (= > 37 years old) were divided into 2 groups: the AMH high (H) group and the AMH low (L) group. The parameters of in vitro embryo development and clinical outcomes were compared between the two groups. The results showed that women in the L group experienced severe DOR, as demonstrated by a higher rate of primary diagnosis of DOR, lower antral follicle count (AFC), higher level of basal follicle stimulating hormone (FSH) and cancelation cycles, lower level of E2 production on the day of surge, and fewer oocytes and MII oocytes retrieved. Compared with women in the H group, women in the L group showed slightly reduced top embryo formation rate but a similar normal fertilization rate and blastocyst formation rate. More importantly, we found that the rates of implantation, spontaneous miscarriage and livebirth were similar between the two groups, while the pregnancy rate was significantly reduced in the L group compared with the H group. Further analysis indicated that the higher pregnancy rate of women in the H group may be due to more top embryos transferred per cycle. Due to an extremely low implantation potential for transfer of non-top embryos from WAA (= > 37 years old) in our reproductive centre, we assumed that all the embryos that implanted may result from the transfer of top embryos. Based on this observation, we found that the ratio of embryos that successfully implanted or eventually led to a livebirth to top embryos transferred was similar between the H and the L groups. Furthermore, women with clinical pregnancy or livebirth in the H or L group did not show a higher level of serum AMH but were younger than women with non-pregnancy or non-livebirth. Taken together, this study showed that AMH had a limited role in predicting in vitro embryo developmental potential and had no role in predicting the in vivo embryo developmental potential, suggesting that in WAA, AMH should not be used as a marker of oocyte quality. This study supports the view that the accumulation of top embryos via multiple oocyte retrieval times is a good strategy for the treatment of WAA.

Differences in the Potential Accessibility of Home-Based Healthcare Services among Different Groups of Older Adults: A Case from Shaanxi Province, China.

With the increase of the aging population and the lack of family care, home-based healthcare services have gradually become the main model to cope with aging, so local governments have invested heavily in the construction of home-based healthcare services. However, healthcare services still have problems such as low resource utilization and imbalanced development. The reason is that the supply and demand of healthcare services are not matched and the potential accessibility is low. Therefore, based on the supply and demand of healthcare services, this article pulls out the spatial and social factors that affect the potential accessibility, and tests the influence of individual factors on the potential accessibility among different groups of older adults. It is found that the perceived vulnerability of the older adults will reduce the potential accessibility of healthcare services. The psychosocial status, income and education level with the willingness to use healthcare services of the older adults are directly proportional, while residence has a negative impact on the potential accessibility. Finally, based on this finding, this article puts forward feasible suggestions from the perspective of policy content, publicity, and implementation.

Family Support, Multidimensional Health, and Living Satisfaction among the Elderly: A Case from Shaanxi Province, China.

The current study investigated the association between three types of family support and living satisfaction of elderly individuals in China, and paid particular attention to the possible mediating role of the elderly population's multidimensional health. A cross-sectional survey was conducted in 2019, and 938 elderly people from seven counties (districts) of China's Shaanxi province were enrolled. Multivariable linear regression and mediation effect analysis were employed to examine the integrated relationships among these variables. The results showed that emotional support and decisional support from families were positively related to the living satisfaction of elderly individuals (ß = 0.101, p = 0.000; ß = 0.263, p = 0.000), while the relationship between daily living support and living satisfaction was not significant (ß = 0.017, p > 0.05). The mediation examination further demonstrated that both mental state and social integration mediated the association between emotional support and living satisfaction, as well as the association between decisional support and living satisfaction, but a mediating effect of physical health was not observed. These results indicate the pathways in the relationships of different types of family support to living satisfaction via mental state and social integration, having significant implications for enhancing the living satisfaction the elderly.

Assessing the Accessibility of Home-Based Healthcare Services for the Elderly: A Case from Shaanxi Province, China.

With the rapid increase of the elderly population in China, healthcare services for the elderly have gradually become an important welfare resource. However, the healthcare service for the elderly still has problems such as mismatched supply and demand and unbalanced resources. In order to effectively eliminate the path barriers to match supply and demand, and improve the accessibility of healthcare services, this paper introduces the sustainability of the healthcare service based on the accessibility theory, and constructs an index system from the three dimensions of potential accessibility, realized accessibility, and sustainable accessibility of healthcare services for the elderly. Then, the paper makes a practice application of the index system based on survey data of healthcare services from Shaanxi province, China. Finally, the paper finds that the total accessibility and sustainable accessibility of healthcare services for the elderly in Shaanxi Province are at an average level. The score of potential accessibility is high, indicating that elderly people have greater opportunities to use healthcare services. The realized accessibility score is low, which indicates that the actual use of healthcare services for the elderly presents low satisfaction.

The Effects of China's Targeted Poverty Alleviation Policy on the Health and Health Equity of Rural Poor Residents: Evidence from Shaanxi Province.

Objective: China's targeted poverty alleviation policy has a profound impact on the country's rural economic and social development now. This study aimed to learn about the health status and health equity of rural poor residents under the implementation of the policy. It further explores the factors affecting the health status and health equity of rural poor residents in order to contribute to the improvement of the policy. Methods: The data of 1233 rural poor residents were collected from a questionnaire survey from 12 prefecture-level cities and areas of Shaanxi province in 2017, and the self-reported health was used to reflect the health status. A concentration index was applied to measure the inequity of the health status of rural poor residents. The decomposition method was employed to explore the source of health inequity. Results: The results showed that 44.56% of rural poor residents in Shaanxi province had a poor or very poor health status, which was affected by their economic level, gender, age, degree of education, and marital status. Additionally, participation in agricultural industry development, relocation, health poverty alleviation, and basic living standards were significantly correlated with health status. The concentration index of the health status of rural poor residents was 0.0327. The primary contributors to the health inequity in different regions varied, but the economic level and the degree of education were the most significant factors, and the targeted poverty alleviation policy had a significant impact on health equity. Conclusions: The results indicated that the health status of rural poor residents in Shaanxi province was generally poor, there was a pro-rich inequity in the health status, and the degree of education and economic level were the primary factors affecting the health status and health equity. The targeted poverty alleviation policy greatly impacted the health status and health equity of rural poor residents, and the difference in health status would lead to the inequity of benefits of the targeted poverty alleviation policy. In the future, the policy should focus on ensuring the sustainable development ability of rural residents with poor health status.

BMI1 promotes steroidogenesis through maintaining redox homeostasis in mouse MLTC-1 and primary Leydig cells.

In males, aging is accompanied by decline in serum testosterone levels due to impairment of testicular Leydig cells. The polycomb protein BMI1 has recently been identified as an anti-aging factor. In our previous study, BMI1 null mice showed decreased serum testosterone and Leydig cell population, excessive oxidative stress and p16/p19 signaling activation. However, a cause-and-effect relationship between phenotypes and pathways was not investigated. Here, we used the rescue approach to study the role of oxidative stress or p16/p19 in BMI1-mediated steroidogenesis. Our results revealed that treatment with antioxidant NAC, but not down-regulation of p16/p19, largely rescued cell senescence, DNA damage and steroidogenesis in BMI1-deficient mouse MLTC-1 and primary Leydig cells. Collectively, our study demonstrates that BMI1 orchestrates steroidogenesis mainly through maintaining redox homeostasis, and thus, BMI1 may be a novel and potential therapeutic target for treatment of hypogonadism.

Sperm enrichment from poor semen samples by double density gradient centrifugation in combination with swim-up for IVF cycles.

Sperm preparation in IVF cycles using density gradient centrifugation (DGC) in combination with swim-up (SU) has been widely adopted in reproductive centres worldwide. It is a fact that the sperm recovery rate following one DGC from poor semen samples (showing liquefaction defects/containing too many unresolvable clots or rare sperm) is relatively low. Our results showed that double DGC (DDGC) is effective at increasing the sperm recovery rate from poor semen samples. However, DDGC may increase the mechanical stress of sperm, thereby potentially impairing embryo development. Therefore, it is necessary to evaluate the safety of using sperm prepared by DDGC/SU for IVF cycles. In this study, we retrospectively analysed the data generated from a total of 529 IVF cycles (from June 2017 to June 2018), and these IVF cycles contributed 622 transfer cycles (from June 2017 to December 2018) in Changzhou Maternal and Child Health Care Hospital. Of them, 306 IVF cycles and the related 355 transfer cycles (normal semen samples prepared by DGC/SU) were set as the normal group, while 223 IVF cycles and the related 267 transfer cycles (poor semen prepared by DDGC/SU) were set as the observation group. The main outcome measures, including the normal fertilization rate, top D3 embryo formation rate, blastocyte formation rate, clinical pregnancy rate and live birth rate, birth weight and duration of pregnancy, were compared between the two groups. Compared to semen in the DGC/SU group, semen in the DDGC/SU group showed increased levels of the DNA fragmentation index (DFI) and reduced sperm concentration, percentage of progressive motility (PR) sperm, and percentage of normal morphology sperm. The indicators reflecting in vitro embryo development and clinical outcomes were similar in the DGC/SU group and DDGC/SU group, including the normal fertilization rate, top D3 embryo formation rate, blastocyte formation rate, pregnancy rate, implantation rate, spontaneous abortion rate, live birth rate, birth weight and duration of pregnancy. Furthermore, we found that the 1PN zygote formation rate was significantly lower in the DDGC/SU group than that in the DGC/SU group. We concluded that oocytes fertilized by sperm from poor semen samples separated by DDGC/SU achieved the same outcomes as oocytes fertilized by sperm from normal semen separated by DGC/SU, suggesting that DDGC/SU is an effective and safe method of sperm enrichment for poor semen samples in IVF. The main contribution of the present study is the verification of the effectiveness of DDGC/SU in improving sperm recovery from poor semen samples and the safety of using sperm prepared by DDGC/SU for IVF.

Up-regulation of PTEN via LPS/AP-1/NF-κB pathway inhibits trophoblast invasion contributing to preeclampsia.

Preeclampsia, a pregnancy-specific disorder, is characterized by abnormal vascular remodeling of the spiral arteries due to deficient trophoblast invasion. Lipopolysaccharide (LPS) administration to pregnant rats on day 5 of pregnancy could induce excessive immune response at the maternal-fetal interface contributing to poor early placentation that culminate in the preeclampsia-like syndrome. Furthermore, the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a critical tumor suppressor, is markedly increased in the placentas of patients with preeclampsia. Our goal was to investigate the association of PTEN with preeclampsia and the pathways involved using human-trophoblast-derived cell line (HTR-8/SVneo) stimulated with LPS. We found that the expression of PTEN was significantly increased in the placentas of patients with severe preeclampsia and preeclamptic rat model induced by LPS. In vitro trophoblasts results showed that significantly differential expression of PTEN with corresponding changes in JunB/FosB (subunits of AP-1) and NF-κB activity after LPS stimulation. We further demonstrated that LPS-induced PTEN expression was dependent on AP-1 and NF-κB in trophoblasts. The trophoblasts with enforced expression of PTEN showed a reduced ability to invasion. Taken together, LPS may undermine remodelling of the human-trophoblast-derived HTR-8/SVneo cells by increasing PTEN, acting in part through the AP-1 and NF-κB pathways.