Global, regional, and national time trends in incidence, prevalence, years lived with disability for uterine fibroids, 1990-2019: an age-period-cohort analysis for the global burden of disease 2019 study.

BACKGROUND: Uterine fibroids are the most common benign neoplasm of the uterus and a major source of morbidity for women. We report an overview of trends in uterine fibroids of incidence rate, prevalence rate, years lived with disability (YLDs) rate in 204 countries and territories over the past 30 years and associations with age, period, and birth cohort. METHODS: The incident case, incidence rate, age-standardized rate (ASR) for incidence, prevalent case, prevalence rate, ASR for prevalence, number of YLDs, YLD rate, and ASR for YLDs were derived from the Global Burden of Disease 2019 (GBD 2019) study. We utilized an age-period-cohort (APC) model to estimate overall annual percentage changes in the rate of incidence, prevalence, and YLDs (net drifts), annual percentage changes from 10 to 14 years to 65-69 years (local drifts), period and cohort relative risks (period/cohort effects) between 1990 and 2019. RESULTS: Globally, the incident cases, prevalent cases, and the number of YLDs of uterine fibroids increased from 1990 to 2019 with the growth of 67.07%, 78.82% and 77.34%, respectively. High Socio-demographic Index (SDI) and high-middle SDI quintiles with decreasing trends (net drift < 0.0%), and increasing trends (net drift > 0.0%) were observed in middle SDI, low-middle SDI, and low SDI quintiles in annual percentage change of incidence rate, prevalence rate and YLDs rate over the past 30 years. There were 186 countries and territories that showed an increasing trend in incidence rate, 183 showed an increasing trend in prevalence rate and 174 showed an increasing trend in YLDs rate. Moreover, the effects of age on uterine fibroids increased with age and peaked at 35-44 years and then declined with advancing age. Both the period and cohort effects on uterine fibroids showed increasing trend in middle SDI, low-middle SDI and low SDI quintiles in recent 15 years and birth cohort later than 1965. CONCLUSIONS: The global burden of uterine fibroids is becoming more serious in middle SDI, low-middle SDI and low SDI quintiles. Raising awareness of uterine fibroids, increasing medical investment and improving levels of medical care are necessary to reduce future burden.

In utero bisphenol A exposure disturbs germ cell cyst breakdown through the PI3k/Akt signaling pathway and BDNF expression.

PURPOSE: To determine the influence of the environmental endocrine disruptor bisphenol A (BPA) on germ cell cyst breakdown and explore the possible mechanisms regulating this activity. METHODS: BPA (2 µg/kg/d or 20 µg/kg/d) or tocopherol-stripped corn oil (vehicle control) was administered to pregnant mice by gavage at gestational day 11, and the offspring (prenatally treated mice) were sacrificed and ovariectomized at postnatal day (PND) 4 and PND22. Ovarian morphology was documented in the first filial (F1) generation female offspring, and the follicles were analyzed and classified morphologically on PND 4. To discover differentially expressed genes and associated target pathways, we used RNA-seq, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Gene Ontology (GO) analysis. The mRNA expression of key steroid hormone synthesis-related genes was evaluated by Q-PCR in forskolin-induced KGN cells. Western blotting (WB) and qRTPCR were used to determine the protein and gene expression levels of brain-derived neurotrophic factor (BDNF). RESULTS: BPA, a typical endocrine disrupting chemical (EDC), decreased the expression of the key steroid hormone synthesis-related genes P450scc and aromatase, while the expression of Star increased significantly and caused no significant difference in the expression of Cyp17a1 or HSD3ß in forskolin-induced KGN cells. Moreover, we confirmed that in utero exposure to environmentally relevant concentrations of BPA (2 µg/kg/d and 20 µg/kg/d) could significantly disrupt germ cell cyst breakdown, leading to the generation of fewer primordial follicles than in the control group. The factors mediating the inhibitory effects included the PI3K-Akt signaling pathway and a significant downregulation of BDNF. CONCLUSIONS: These findings indicate that in utero exposure to BPA at low doses, which are lower than recommended as 'safe' dosages, may influence the formation of primordial follicles by inhibiting the expression of steroid hormone synthesis-related genes and partly by regulating the BDNF-mediated PI3K/Akt pathway.

Relationship between years since menopause and lipid variation in postmenopausal women: A cross-sectional study.

Lipid alteration in postmenopausal women is commonly due to hormonal changes. This study aimed to explore the association between the years since menopause and lipid profiles in postmenopausal women. In this cross-sectional study, a total of 1033 postmenopausal women were recruited from the Women's Hospital of Zhejiang University in China between 2015 and 2022. Each participant was interviewed using questionnaires regarding sociodemographic and reproductive data. Anthropometric measurements, lipid profiles, and reproductive hormone levels were assessed. Participants were divided into 3 groups based on the length of time since menopause: 2, 2 to 5.9, and 6 years. Differences in lipid profiles and reproductive hormones among the groups were compared. Logistic and linear regression analyses were used to examine the relationship between years after menopause and lipid profile. High-density lipoprotein cholesterol (HDL-C) and luteinizing hormone levels were significantly lower in postmenopausal women with time since menopause of ≥6 years than those <2 years (P < .05), whereas low-density lipoprotein cholesterol levels were significantly higher (P < .05). A longer time after menopause was independently associated with lower HDL-C levels (ß, -0.059, standard error, 0.023, P = .01) after adjustment for age, body mass index, and other confounders. Compared to women who had menopause for <2 years, those who were postmenopausal for >6 years had lower HDL-C levels after adjustment for age, body mass index, and other covariates (ß, -0.123, 95% confidence interval, [-0.221, -0.014], P = .014). Longer time since menopause was associated with an atherogenic lipid profile with appreciably low levels of HDL-C subfraction. Future multicenter studies are necessary to examine postmenopausal population and determine how differences in lipids influence the risk of cardiovascular disease in this group.

Clinical observation of menopause hormone therapy in postmenopausal women with euthyroid and mild subclinical hypothyroidism.

BACKGROUND: To evaluate the endocrine hormone and metabolic indices in postmenopausal women with euthyroid and mild subclinical hypothyroidism after menopause hormone therapy (MHT). METHODS: A retrospective study of 587 postmenopausal women receiving MHT was conducted. Median (25-75th percentile) age was 52 (49-54) years. According to thyroid stimulating hormone (TSH) levels at initial diagnosis, the patients were divided into three groups: I (euthyroid with low normal TSH range, n = 460), II (euthyroid with upper normal TSH range, n = 106) and III (mild subclinical hypothyroidism, n = 21). After a continuous oral MHT regimen using the same estradiol potency for 6-18 month cycles, serum endocrine hormone and metabolic indices were reassessed. RESULTS: Compared with baseline, serum TSH levels in groups I and II significantly changed but all values were within the normal range. No significant difference was observed in serum TSH levels in group III. After treatment, all serum free tri-iodothyronine and free thyroxine levels were within the normal range. Serum total cholesterol, triglyceride, fasting plasma glucose, fasting insulin levels and homeostasis model assessment of insulin resistance index had significantly decreased in group I. There were no significant differences in all observed lipid and glucose parameters in group III, before and after treatment. CONCLUSION: MHT did not affect thyroid function in postmenopausal women with euthyroid and mild subclinical hypothyroidism. MHT led to an improvement in lipid and glucose indicators in euthyroid women with low normal TSH range.

Occupational hazards and the onset of natural menopause.

OBJECTIVE: To identify occupational hazards associated with earlier onset of natural menopause. STUDY DESIGN: A national cross-sectional study was conducted to explore the reproductive health of Chinese female workers. The final sample size was 17,948. MAIN OUTCOME MEASURES: Participants completed a self-report instrument that recorded working conditions, chemical and physical agents in the occupational environment, socioeconomic factors, lifestyle, reproductive history, and occupational information. A Cox regression model was used to examine the association between each occupational hazard and onset of menopause. RESULTS: Abnormal workload (19.31 %), aromatic compounds (7.95 %), and noise (24.94 %) were the three most frequently self-reported occupational hazards in the three categories of working conditions, chemical agents, and physical agents, respectively. Abnormal workload (HR = 1.133, p = 0.038), noise (HR = 1.233, p < 0.001), and heat stress (HR = 1.178, p = 0.041) were associated with earlier age at natural menopause in the analyses of each hazard, after adjustment. Only noise (HR = 1.187, p = 0.003) remained statistically significant after including all possible occupational hazards. CONCLUSIONS: In a national survey of 17,948 female workers, this study investigated the association of age at natural menopause with multiple occupational hazards, some of which have not been addressed. Occupational noise was identified as a risk factor for reproductive senescence for the first time. However, further research is needed to confirm our findings.

Biopsychosocial risk factors of depression during menopause transition in southeast China.

OBJECTIVE: More than 2 billion women are experiencing menopause transition in China and some of them suffered from depression; while the risk factors of depression during menopause transition were still unclearin China. We aimed to investigate the risk factors in mid-life women in Southeast China. METHOD: This study included 1748 Chinese women aged 40-65 years-old who visited gynecology outpatient department of Women's hospital School of Medicine, Zhejiang University during 2010-2018. Demographic information was collected, and the modified Kupperman Menopausal Index (mKMI) and Hamilton Rating Scale for Depression were assessed. Circulating levels of sex hormones were tested. Ordinal logistic regression analysis was performed to identify risk factors for depression. RESULTS: The prevalence of depression symptoms was 47.43%. The majority of women had mild (38.56%) or moderate depressive symptoms (8.00%); only 0.86% had severe depressive symptoms. Compared with perimenopausal women, postmenopausal women had increased risks of more severe depression. The associations between menopausal syndromes and the intensity of depression were strongly positive (OR 6.69, 95% CI 5.39-8.29). Elder age, higher follicle stimulating hormone levels, lower estradiol levels, and fewer parity were positively related with the intensity of depression. Among postmenopausal women, underweight, mKMI > 14, earlier age at menopause, shorter reproductive period, and longer duration after menopause were risk factors for incresed intensity of depression. CONCLUSIONS: The results demonstrated a high proportion of depression in women complaining of menopause. Menopausal symptoms were strongly related to the intensity of depression. In postmenopausal women, estrogen related events are associated with the intensity of depression. Gynecological endocrinologists in China should consider screening for depression in high-risk women.

Association between serum vitamin A levels and premature ovarian insufficiency: a case-control, cross-sectional survey study.

BACKGROUND: Although vitamin A is known to play an important role in ovarian function, its association with ovarian insufficiency has not been reported yet. Therefore, the aim of the study was to explore the association between serum vitamin A levels and premature ovarian insufficiency (POI). METHODS: This cross-sectional survey included women with POI (n = 47) and normo-ovulatory controls (n = 67) who were enrolled between December 2016 and May 2018 in Zhejiang, China. The serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), anti-Müllerian hormone (AMH), vitamin A, and total cholesterol (TC) were measured for each participant. The association of TC-adjusted vitamin A levels with the risk of POI was assessed using binary logistic regression analysis. RESULTS: Serum vitamin A levels appeared to be slightly higher in the POI group than in the control group, but there was no evidence of a statistically significant difference (728.00 ± 176.00 µg/L vs. 503.93 ± 145.64 µg/L, p = 0.13). After adjustment for serum lipid levels, the serum vitamin A/TC ratio was significantly lower in the POI group than in the control group (143.14 ± 35.86 vs. 157.56 ± 35.21 µg/mmol, p = 0.04). Further, the serum vitamin A/TC ratio was significantly and inversely associated with POI risk (unadjusted odds ratio [OR] = 0.988, 95% confidence interval [CI]: 0.977-0.999, p = 0.04). The association remained after adjusting for confounding factors (age, BMI, annual household income, and education) (OR = 0.986, 95% CI: 0.972-0.999, p = 0.04). CONCLUSIONS: Serum vitamin A/TC ratio was inversely associated with POI risk. Therefore, the serum vitamin A/TC ratio may serve as a predictive factor for POI, and vitamin A supplementation may play help prevent or treat POI.

Upregulation of h-TERT and Ki-67 in ectopic endometrium is associated with recurrence of endometriosis.

At present, endometriosis remains a worldwide health burden, with the main symptoms of dysmenorrhea, chronic pelvic pain, and infertility, markedly reducing the quality of life (de Ziegler et al., 2010). Although there is no proof that the disease is associated with high mortality, this disorder can significantly contribute to the deterioration of women's general well-being (McPeak et al., 2018). The main current treatment for endometriosis is surgery to remove endometriotic lesions; however, the recurrence rate following surgical treatment is as high as 21.5% at two years and 40.0%|-|50.0% at five years post-surgery (Koga et al., 2015). To prevent recurrence, adjuvant treatment with drugs after surgery is recommended to prolong relapse-free intervals. However, it is inconvenient for patients to continuously use such medications in terms of adverse effects and cost (Turk, 2002).

Change in metabolic parameters and reproductive hormones from baseline to 6-month hormone therapy.

ABSTRACT: Adequate evidence showed hormone therapy (HT) reduces the risk of new-onset diabetes in midlife women by decreasing fasting glucose and insulin. However, the improvement of these diabetic biomarkers varied with each individual in clinical observations. The objective of our study was to investigate potential baseline factors associated with the change of fasting glucose and insulin during HT.A retrospective cohort study was performed among 263 midlife participants aged 40 to 60 years with menopausal symptoms who have received 6-month individualized HT. Demographic information and laboratory indicators including reproductive hormone, lipid profiles, diabetic indicators were collected and measured at baseline and were followed-up. A series of statistical analyses were performed to confirm the effectiveness of HT and compare the baseline factors between participants with different glycemic or insulinemic response. Multivariable linear regression model with stepwise variable selection was further used to identify the associated factor with the change of fasting glucose and insulin.Of all participants, fasting glucose (P = .001) and fasting insulin (P < .001) were significantly decreased after individualized HT. Significant differences in baseline reproductive hormones were observed in participants with different glycemic response to HT (P < .001 for both follicle stimulating hormone [FSH] and estradiol). Stepwise linear regression model showed that in addition to baseline fasting glucose levels, baseline FSH was also independently associated with the change of fasting glucose (ß = -0.145, P = .019 for baseline FSH) but not fasting insulin. Greater reduction in fasting glucose in women with higher FSH levels was observed even though they have already been in better metabolic conditions (P = .037).Midlife women with higher baseline FSH levels have greater reduction in fasting glucose but not fasting insulin. FSH could be an independent predictor of glycemic response to HT in peri- and postmenopausal women.

Effects of hormone replacement therapy on glucose and lipid metabolism in peri- and postmenopausal women with a history of menstrual disorders.

BACKGROUND: Previous studies have indicated that women with a history of menstrual disorders have an increased risk of metabolic and cardiovascular diseases. This has been attributed to the high proportion of polycystic ovary syndrome (PCOS) among this group. The favorable effects of hormone replacement therapy (HRT) on serum lipid profiles and glucose homeostasis in postmenopausal women is widely accepted. Whether HRT can also show positive effects on metabolic homeostasis in menopausal women with prior menstrual disorders (a putative PCOS phenotype) has not been reported yet. The aim of the study was to compare the effects of HRT on glucose and lipid metabolism in peri- and postmenopausal women with prior menstrual disorders and controls who did not have prior menstrual disorders. METHODS: A retrospective multicenter study was conducted including 595 peri- and postmenopausal women who received HRT at four hospitals in the Zhejiang Province from May 31, 2010 to March 8, 2021. Participants were divided into the Normal menstruation group and the Menstrual disorders group according to their prior usual menstrual cycle pattern. Glucose and lipid metabolism indicators were assessed at baseline and after HRT. The results were compared between and within the groups, and data from peri- and postmenopausal women were analyzed separately. RESULTS: HRT significantly decreased fasting insulin and homeostasis model assessment of insulin resistance in perimenopausal users, and fasting plasma glucose levels in postmenopausal users with prior menstrual disorders, compared with baseline. Furthermore, HRT decreased low-density lipoprotein cholesterol, total cholesterol, fasting insulin, fasting plasma glucose and homeostasis model assessment of insulin resistance in both peri- and postmenopausal controls, compared with baseline. Nevertheless, no significant differences were observed in any of the glucose or lipid metabolism indicators at baseline and follow-up, as well as changes from baseline levels between menopausal women with and without prior menstrual disorders. CONCLUSIONS: HRT shows more obvious within-group improvements in glucose and lipid metabolism in controls, but there is no significant between-group difference. Further prospective studies are required for confirmation.

Metabolic profile of women with premature ovarian insufficiency compared with that of age-matched healthy controls.

OBJECTIVE: . To compare the metabolic profile of women with spontaneous premature ovarian insufficiency (POI) with that of age-matched healthy controls. STUDY DESIGN: . A cross-sectional case-control study was conducted using 1:1 matching by age. Women below the age of 40 with spontaneous POI who did not receive any medication (n = 303) and age-matched healthy women (n = 303) were included in this study. MAIN OUTCOME MEASURES: . Metabolic profiles, including serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), glucose, uric acid, urea and creatinine, were compared between women with POI and controls. For women with POI, factors associated with the metabolic profile were analyzed. RESULTS: . Women with POI were more likely to exhibit increased serum levels of TG (ß, 0.155; 95% CI, 0.086, 0.223) and glucose (0.067; 0.052, 0.083), decreased levels of HDL-C (-0.087; -0.123, -0.051), LDL-C (-0.047; -0.091, -0.003) and uric acid (-0.053; -0.090, -0.015), and impaired kidney function (urea [0.070; 0.033, 0.107]; creatinine [0.277; 0.256, 0.299]; eGFR [-0.234; -0.252, -0.216]) compared with controls after adjusting for age and BMI. BMI, parity, gravidity, FSH and E2 levels were independent factors associated with the metabolic profile of women with POI. CONCLUSION: . Women with POI exhibited abnormalities in lipid metabolism, glucose metabolism, and a decrease in kidney function. In women with POI, early detection and lifelong management of metabolic abnormalities are needed.

Menopausal symptoms in women with premature ovarian insufficiency: prevalence, severity, and associated factors.

OBJECTIVE: To comprehensively investigate and evaluate the prevalence, severity, and associated factors of menopausal symptoms in women with premature ovarian insufficiency (POI). In this study, the specific symptomatology experienced by women with POI and women with natural menopause was also compared. METHODS: In this cross-sectional study, 293 Chinese women with POI from an outpatient clinic were recruited between June 2014 and January 2019. The prevalence and severity of menopausal symptoms were assessed with modified Kupperman Menopausal Index. Participants completed a structured questionnaire, including medical history, menstrual characteristics, and sociodemographic data. Serum levels of reproductive hormones were measured. RESULTS: Among 293 women with POI (33.76 ±â€Š5.47 y), the most prevalent symptoms were mood swings (73.4%), insomnia (58.7%), sexual problems (58.7%), and fatigue (57.3%). Moderate-to-severe mood swings were most frequently reported (23.9%), followed by formication (17.4%) and hot flashes/sweating (17.1%). Compared with women with natural menopause, women with POI exhibited significantly higher risks for fatigue (odds ratio  = 1.42; 95% confidence interval, 1.04-1.94), melancholia (3.12; 1.94-5.01), mood swings (3.57; 2.33-5.45), insomnia (1.41; 1.02-1.96), and significantly lower risks for moderate-to-severe sexual problems (0.40; 0.23-0.69), any and moderate-to-severe muscle/joint pain (0.41; 0.27-0.62 and 0.45; 0.25-0.78, respectively). Living in urban areas and higher gravidity were independently associated with menopausal symptoms in women with POI. CONCLUSIONS: Women with POI experienced a high prevalence of menopausal symptoms, particularly related to psychological and sexual domains. Furthermore, women with POI tended to have more distressing menopausal symptoms compared with women with natural menopause.

Associations of age at natural menopause and occupations in Chinese female workers: A cross-sectional study.

AIMS: To investigate the impact of occupation types on age at natural menopause. METHODS: This is a nation-wide cross-sectional study based on 17,948 female workers aged over 40, who come from different industries or organizations. A face-to-face standardized questionnaire was conducted in all participants with the help of occupational hygienists. Occupational titles were coded according to the International Standard Classification of Occupations (2008) (ISCO08). Cox regression model was used to assess the association between each independent occupation and menopausal timing. Models were adjusted for marriage, education, average annual family income, parity, cigarette smoking, alcohol consumption. RESULTS: Higher risks of earlier age at natural menopause was found among legislators and senior officials (ISCO Minor group:111, HR = 2.328, P < 0.001), among other health associated professionals (ISCO Minor group: 325, HR = 1.477, P = 0.003), the workers involved in mining and mineral processing (ISCO Minor group: 811, HR = 1.515, P = 0.048) and metal processing and finishing (ISCO Minor group: 812, HR = 1.722, P < 0.001). Reduced risks of earlier age at natural menopause, including: finance professionals (ISCO Minor group: 241, HR = 0.751, P = 0.021), manufacturing and construction supervisors (ISCO Minor group: 312, HR = 0.477, P = 0.002), administrative and specialized secretaries (ISCO Minor group: 334, HR = 0.788, P = 0.045), cleaners and helpers (ISCO Minor group: 911, HR = 0.633, P = 0.01). CONCLUSIONS: This is the first study to address the influence of occupation types on reproductive aging, showing some specific occupations could be associated with age at natural menopause. Further investigations are necessary to clarify whether it is chance finding or a true association.

Risk Factors of Intra-Amniotic Infection Related to Induction with Single-Balloon Catheter: A Case-Control Study.

AIMS: To investigate the risk factors of intra-amniotic infection (IAI) related to induction with single-balloon catheter (SBC). METHODS: A retrospective, case-control study including 58 cases of IAI patients who underwent induction with SBC was conducted in Women's Hospital, School of Medicine, Zhejiang University. For each case, 8 women who delivered during the same month and had no infection after SBC induction were selected for control. RESULTS: Compared with the control group, the IAI group had a higher rate of nulliparity (87.93 vs. 70.69%; p = 0.006), BMI > 30 kg/m2 (29.31 vs. 15.95%; p = 0.011), and amniotic fluid index (AFI) < 8 cm (32.8 vs. 15.1%; p = 0.001). The diameter of cervical dilatation when membranes ruptured in IAI group was smaller than that in the control group (2.0 [1.5] vs. 3.0 [8.0] cm; p < 0.001). Time from start of induction to vaginal delivery was longer than that in the control group (47.0 [19.75] vs. 27.0 [16.0] h; p < 0.001). After logistic regression, the 5 factors associated with IAI for those who underwent SBC induction were nulliparity, BMI > 30 kg/m2, AFI < 8 cm, diameter of cervical dilatation < 3 cm when membranes ruptured and time from start of induction to vaginal delivery of more than 48 h. CONCLUSIONS: Focus on these risk factors could result in earlier prophylaxis so that the incidence of IAI could be reduced.

Higher level of circulating estradiol is associated with lower frequency of cognitive impairment in Southeast China.

BACKGROUND: Estrogen has been proved to have positive effects on the brain cognitive function. However, many clinical studies investigating the associations between cognitive functions and circulating estrogen levels in perimenopausal and postmenopausal women demonstrated controversial results. METHOD: Circulating estradiol and follicle stimulating hormone (FSH) levels were obtained from 199 perimenopausal and postmenopausal women (mean age: 49.61 years). The cognitive function has been assessed using the Beijing version of the Montreal Cognitive Assessment. RESULTS: Results revealed that higher estradiol levels were associated with better cognitive function (p < 0.05) both in perimenopausal and postmenopausal women and levels of FSH were unrelated to cognitive performance. CONCLUSIONS: In perimenopausal and postmenopausal women, higher levels of circulating estradiol are associated with lower risk of cognitive impairment.

No effect of energy intake overall on risk of endometrial cancers: a meta-analysis.

BACKGROUND: Previous epidemiologic studies on the association between energy intake and endometrial cancer risk have only generated contradictory results. The role of energy intake in endometrial carcinogenesis thus remains unclear. To quantitatively assess the potential association between energy intake and endometrial cancer, a meta-analysis of case-control and cohort studies was here conducted. MATERIALS AND METHODS: Eligible studies were retrieved via both computerized searches and review of references. Fixed-or random-effect models were used to summarize the estimates of OR with 95%CIs. Stratified analyses on study design, region and macronutrients' calorie were performed. RESULTS: Sixteen studies met the inclusion criteria of the meta-analysis. No association between total energy intake and endometrial cancer was observed in either overall group (OR=1.11, 95%CI 0.92-1.30) or subgroups stratified by study design and region. In the specific macronutrients' calorie analysis, higher fat energy intake was found to be associated with increased endometrial risk (OR=1.72, 95%CI 1.12- 2.32) while energy from carbohydrate and protein was not related to endometrial cancer risk. CONCLUSIONS: Our analysis did not support that total energy intake is related to endometrial cancer risk, in contrast to fat energy.

EGB1212 post-treatment ameliorates hippocampal CA1 neuronal death and memory impairment induced by transient global cerebral ischemia/reperfusion.

Extracts of Ginkgo biloba have been used in traditional medicines for centuries, and have potential for clinical applications in cerebral ischemia/reperfusion injury. However, standardized extracts have proven protective only as pre-treatments, and the major mechanisms of action remain unclear. We explored the potential of the novel extract EGB1212, which meets the United States Pharmacopeia (USP) 31 standardization criteria for pharmaceutical use, as a post-treatment after global cerebral ischemia/reperfusion (GCI/R) injury in a rat model. The pre-treated group was administered EGB1212 for 7 d prior to common carotid artery occlusion (i.e., ischemia, for 20 min). Post-treated rats received the same but starting 2 h after ischemia and continuing for 7 d. Seven days after GCI/R, brains of each group were processed for H&E staining of hippocampal CA1 neurons. Remaining rats underwent the Morris water maze and Y-maze tests of spatial learning and memory, beginning eight days after reperfusion. To assess hippocampal autophagy, light chain (LC)-3-I/LC3-II and Akt/pAkt were determined via a Western blot of rat hippocampi harvested 12, 24, or 72 h after reperfusion. EGB1212 pre- and post-treatments both improved neuronal survival and spatial learning and memory functions. Pre-treatment effectively reduced LC3-II levels and post-treatment resulted in significantly elevated pAkt levels. We conclude that EGB1212 exerted significant neuroprotection in GCI/R in both preventative and post-treatment settings. This extract shows great potential for clinical applications.

A systematic review and meta-analysis of buyang huanwu decoction in animal model of focal cerebral ischemia.

Buyang Huanwu Decoction (BHD) is a well-known Chinese herbal prescription for ischemic stroke. The objective of this systematic review and meta-analysis is to provide the current evidence for neuroprotective effects of BHD and its possible mechanisms in animal models of focal ischemia. A systematic literature search, through October 2012, was performed using six databases. The outcome measures assessed were infarct size and/or neurological score. Fifty-six studies with 1270 animals that met the inclusion criteria were identified. The median score for methodological quality was 3 with a range of 2 to 6. Compared with vehicle or no treatment controls, BHD gave a 37% improvement in outcome for all doses ranging from 1.0 g/kg to 60 g/kg at each time point that BHD was administered (P < 0.01). Efficacy was higher in mouse models that utilized suture occlusion and temporary ischemia. The neuroprotective effects of BHD are involved in multiple mechanisms and act upon multiple cell types. In conclusion, BHD possesses substantial neuroprotective effects in experimental stroke probably as a result of the multitarget therapy strategy typically utilized in traditional Chinese medicine. Future research should examine the presence of possible experimental bias and an in-depth study of herbal compound preparations.

Inhibition of P2X7 receptor ameliorates transient global cerebral ischemia/reperfusion injury via modulating inflammatory responses in the rat hippocampus.

BACKGROUND: Neuroinflammation plays an important role in cerebral ischemia/reperfusion (I/R) injury. The P2X7 receptor (P2X7R) has been reported to be involved in the inflammatory response of many central nervous system diseases. However, the role of P2X7Rs in transient global cerebral I/R injury remains unclear. The purpose of this study is to determine the effects of inhibiting the P2X7R in a rat model of transient global cerebral I/R injury, and then to explore the association between the P2X7R and neuroinflammation after transient global cerebral I/R injury. METHODS: Immediately after infusion with the P2X7R antagonists Brilliant blue G (BBG), adenosine 5'-triphosphate-2',3'-dialdehyde (OxATP) or A-438079, 20 minutes of transient global cerebral I/R was induced using the four-vessel occlusion (4-VO) method in rats. Survival rate was calculated, neuronal death in the hippocampal CA1 region was observed using H & E staining, and DNA cleavage was observed by deoxynucleotidyl transferase-mediated UTP nick end labeling TUNEL). In addition, behavioral deficits were measured using the Morris water maze, and RT-PCR and immunohistochemical staining were performed to measure the expression of IL-1ß, TNF-α and IL-6, and to identify activated microglia and astrocytes. RESULTS: The P2X7R antagonists protected against transient global cerebral I/R injury in a dosage-dependent manner. A high dosage of BBG (10 µg) and A-0438079 (3 µg), and a low dosage of OxATP (1 µg) significantly increased survival rates, reduced I/R-induced learning memory deficit, and reduced I/R-induced neuronal death, DNA cleavage, and glial activation and inflammatory cytokine overexpression in the hippocampus. CONCLUSIONS: Our study indicates that inhibiting P2X7Rs protects against transient global cerebral I/R injury by reducing the I/R-induced inflammatory response, which suggests inhibition of P2X7Rs may be a promising therapeutic strategy for clinical treatment of transient global cerebral I/R injury.