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Studies have demonstrated that LIN28 is expressed in the CNS and may exert protective effects on neurons. However, it remains unknown whether LIN28 regulates ferroptosis in the context of epilepsy. In this study, we established an epilepsy model by culturing hippocampal neurons from rats in a magnesium-free (Mg2+-free) medium. In Mg2+-depleted conditions, hippocampal neurons exhibited reduced LIN28 expression, heightened miR-142-5p expression, decreased glutathione peroxidase (GPX) activity and expression, elevated levels of reactive oxygen species (ROS) and malondialdehyde (MDA), resulting in a significant decline in cell viability and an increase in ferroptosis. Conversely, overexpression of LIN28 reversed these trends in the mentioned indices. Altogether, this study reveals that LIN28 may exert neuroprotective effects by inhibiting the miR-142-5p expression and suppressing ferroptosis in hippocampal neurons induced by Mg2+-free via increasing GPX4 expression. [ABSTRACT FROM AUTHOR]

Background: The risk factors for ischemic stroke in young people are complex, varied and closely related to prognosis. This study aims to analyze the risk factors for ischemic stroke in Chinese young people and to explore the main factors influencing the prognosis.Method: A total of 444 patients aged 16 to 45 years with ischemic stroke admitted to Suzhou tertiary hospital from 2011 to 2019 were retrospectively analyzed. Risk factors were identified according to the IPSS definition of pediatric stroke and the TOAST classification. All patients were followed up, and the modified Rankin score was used to evaluate the prognosis. Logistic regression analysis was used to explore the influencing factors of poor prognosis.Results: Among the patients, 12 risk factors were found according to the IPSS definition of pediatric stroke, and 5 types of stroke were found according to the TOAST classification. A total of 299 patients had a good prognosis. Anemia, venous sinus thrombosis, isolated large-vessel occlusion, and high baseline NIHSS score were significant risk factors.Conclusion: The IPSS definition enables patients to be classified on the basis of more risk factors than other classification methods. The prognosis of ischemic stroke in young people is generally good in the 5 years following the event. Anemia, venous sinus thrombosis, isolated large-vessel occlusion and high baseline NIHSS score were associated with poor prognosis. [ABSTRACT FROM AUTHOR]

The microstructures and the mechanical properties of a laser powder bed fusion (LPBF) manufactured alloy coupons that were compositionally graded with austenitic stainless steel 316 L and bronze (Cu10Sn), which are immiscible, were investigated. While the microstructure of the pure 316 L contains only columnar γ-Fe grains, the formation of the equiaxed α-Cu, with α-Fe particles embedded in them, at the grain boundaries of the γ-Fe grains was observed upon alloying with Cu10Sn, for up to 50 wt.%. In the graded alloys with > 50 wt.% Cu10Sn, the microstructure inverts and contains α-Fe particle embedded α-Cu matrix along with some scattered γ-Fe grains. The two-dimensional phase-field simulations were employed to reproduced the phase transition and microstructure evolution in different compositions, revealing that the nucleation of γ-Fe occurs synchronously with the spinodal decomposition of liquid and that with further cooling, Cu-rich liquid solidifies and nanoscale spherical γ-Fe precipitates appear. Cross-sections with 10–40 wt.% Cu10Sn were found structurally unreliable owing to the formation of liquation cracks and shrinkage pores, whereas the rest of the build contained few pores and was crack-free. The Scheil solidification simulations together with the crack susceptibility index calculations over the entire compositions range of the CGA, reveal that when with < 50 wt.% Cu10Sn, liquid feeding to interdendritic regions of γ-Fe is limited, which is otherwise necessary to mitigate shrinkage-induced stresses. The hardness, yield and tensile strengths of the compositionally graded alloy in the cross-section with 50 wt.% Cu10Sn are higher than those of the parent constituents and the one with 80 wt.% Cu10Sn has the best combination of strength and ductility. The variations in strength and ductility are attributed to the microstructural and compositional changes in α-Cu matrix that were influenced by the formation of α-Fe particles. Finally, the appropriate proportions and the influence of the LPBF method in successfully mixing Cu10Sn and SS316L was discussed. [Display omitted] [ABSTRACT FROM AUTHOR]

Environmental susceptibility is an intrinsic property associated with the handling and storage process of nickel-based layered oxide materials in ambient air, which combines with electrochemical factors to determine the cathode performance. Nonetheless, the mechanism underlying such environmental effect has not been well elucidated yet. In this work, using atomic-resolution imaging and spectroscopy, we discover that chemical desodification of Ni-based sodium oxides upon air-exposure triggers extensive initiation and propagation of intragranular cracks along the a-b plane in the lattice, which is distinct from the dense interphase layer for chemically delithiated Ni-based lithium oxides. We rationalize that the diverse environmental susceptibility of Ni-based layered oxides is dictated by Li/Na chemical reaction-diffusion-induced structural evolution or failure, based on the ab initio calculation and numerical kinetic modeling. The established correlation between reaction-diffusion-induced stress fields and structural changes provides new visions for developing high energy and high stability Ni-based layered cathode materials. [Display omitted] [ABSTRACT FROM AUTHOR]

In this paper, we developed a general approach to quantify the uncertainties of interdiffusion coefficients in binary, ternary and multicomponent systems evaluated using the Boltzmann-Matano and related other methods together with the distribution functions. Various sources of errors from both experimental and calculation procedures and their propagation were fully considered and quantified in the finally obtained interdiffusion coefficients. Benchmark tests in hypothetical binary systems with three types of the preset D-c relations and three noise levels were utilized to validate the presently proposed approach, which was then successfully applied in the practical binary, ternary and high-entropy alloys. The comprehensive comparison between the presently calculated interdiffusivities in different alloys with the literature data indicated that the integration of Matano-based methods, the distribution function and the present approach represents a general ensemble solution for evaluation of the reliable interdiffusion coefficients and their uncertainties. Further discussion indicates that the accurate interdiffusion coefficients with reliable uncertainty are the "cornerstone" for the subsequent analysis on diffusion properties, i.e., the sluggish diffusion in high-entropy alloys, and the development of high-quality atomic mobility databases, and the impurity diffusion coefficients with uncertainties can be directly retrieved from the evaluated composition-dependent binary interdiffusion coefficients. Image, graphical abstract [ABSTRACT FROM AUTHOR]

Clinical trials testing infertility treatments often do not report on the major outcomes of interest to patients and clinicians and the public (such as live birth) nor on the harms, including maternal risks during pregnancy and fetal anomalies. This is complicated by the multiple participants in infertility trials which may include a woman (mother), a man (father), and result in a third individual if successful, their offspring (child), who is also the desired outcome of treatment. The primary outcome of interest and many adverse events occur after cessation of infertility treatment and during pregnancy and the puerperium, which create a unique burden of follow-up for clinical trial investigators and participants. In 2013, because of the inconsistencies in trial reporting and the unique aspects of infertility trials not adequately addressed by existing Consolidated Standards of Reporting Trials (CONSORT) statements, we convened a consensus conference in Harbin, China, with the aim of planning modifications to the CONSORT checklist to improve the quality of reporting of clinical trials testing infertility treatment. The consensus group recommended that the preferred primary outcome of all infertility trials is live birth (defined as any delivery of a live infant ≥20 weeks gestations) or cumulative live birth, defined as the live birth per women over a defined time period (or number of treatment cycles). In addition, harms to all participants should be systematically collected and reported, including during the intervention, any resulting pregnancy, and during the neonatal period. Routine information should be collected and reported on both male and female participants in the trial. We propose to track the change in quality that these guidelines may produce in published trials testing infertility treatments. Our ultimate goal is to increase the transparency of benefits and risks of infertility treatments to provide better medical care to affected individuals and couples. [ABSTRACT FROM AUTHOR]

Clinical trials testing infertility treatments often do not report on the major outcomes of interest to patients and clinicians and the public (such as live birth) nor on the harms, including maternal risks during pregnancy and fetal anomalies. This is complicated by the multiple participants in infertility trials which may include a woman (mother), a man (father), and result in a third individual if successful, their offspring (child), who is also the desired outcome of treatment. The primary outcome of interest and many adverse events occur after cessation of infertility treatment and during pregnancy and the puerperium, which create a unique burden of follow-up for clinical trial investigators and participants. In 2013, because of the inconsistencies in trial reporting and the unique aspects of infertility trials not adequately addressed by existing Consolidated Standards of Reporting Trials (CONSORT) statements, we convened a consensus conference in Harbin, China, with the aim of planning modifications to the CONSORT checklist to improve the quality of reporting of clinical trials testing infertility treatment. The consensus group recommended that the preferred primary outcome of all infertility trials is live birth (defined as any delivery of a live infant ≥20 weeks gestations) or cumulative live birth, defined as the live birth per women over a defined time period (or number of treatment cycles). In addition, harms to all participants should be systematically collected and reported, including during the intervention, any resulting pregnancy, and during the neonatal period. Routine information should be collected and reported on both male and female participants in the trial. We propose to track the change in quality that these guidelines may produce in published trials testing infertility treatments. Our ultimate goal is to increase the transparency of benefits and risks of infertility treatments to provide better medical care to affected individuals and couples. [ABSTRACT FROM AUTHOR]

It is difficult to control the heterogeneous nucleation and growth of crystals on porous supports, the preparation of thin ZIF-8 membranes is still extremely challenging. Herein, a two-dimensional transformation strategy is demonstrated for constructing a ZIF-8/GO 'sandwich' composite membrane with a thickness of ∼0.9 μm, which was prepared from Zn-EG-AC (EG: ethylene glycol, AC: CH 3 COO-groups, abbreviated as ZnEG) on alumina hollow fiber support for the first time by precursor conversion method in 2-methylimidazole methanol solution. The effects of the amount of precursor, reaction time and membrane thickness on the membrane structure and H 2 /CO 2 separation performance are explored. The sieving effect of ZIF-8 and the adsorption effect of 2-methylimidazole rings on CO 2 , as well as the strong interaction between GO and CO 2 hinder the permeation of CO 2 into the membrane, thus exhibiting a good H 2 /CO 2 ideal separation selectivity of 30.8 with the H 2 permeance of 1.36 × 10−7 mol·Pa−1·m−2·s−1 under the optimized preparation conditions. The separation factor of the equimolar H 2 /CO 2 binary-mixture gases stabilizes to ∼25 after 30 h. This precursor conversion strategy is expected to be extended to other MOF/graphene oxide (GO) composite membrane systems. Thin ZIF-8/GO sandwich composite membranes can be obtained on alumina hollow fiber supports by a precursor conversion strategy. [Display omitted] • Thin ZIF-8/GO sandwich composite membranes on alumina hollow fibers. • Zinc glycol/GO precursors to ZIF-8/GO membranes by precursor conversion. • The thickness of the high quality ZIF-8/GO membrane is only 0.9 μm. • ZIF-8/GO membranes have considerable H 2 /CO 2 separation selectivity. [ABSTRACT FROM AUTHOR]

Abstract: The use of acupuncture to treat reproductive dysfunction has not been well investigated. Only a few clinical studies have been reported, most of which are flawed by poor design and a lack of valid outcome measures and diagnostic criteria, making the results difficult to interpret. Experimental studies, however, show that acupuncture has substantial effects on reproductive function. Here we review the possible mechanisms of action of acupuncture on the reproductive system and its effects on reproductive dysfunction, focusing in particular on polycystic ovary syndrome, the most common endocrine and metabolic disorder in women. Clinical and experimental evidence demonstrates that acupuncture is a suitable alternative or complement to pharmacological induction of ovulation, without adverse side effects. Clearly, acupuncture modulates endogenous regulatory systems, including the sympathetic nervous system, the endocrine system, and the neuroendocrine system. Randomized clinical trials are warranted to further evaluate the clinical effects of acupuncture in reproductive disorders. [ABSTRACT FROM AUTHOR]

A (tttta)n microsatellite polymorphism in the promoter of CYP11a gene was investigated in 201 Chinese Han women with polycystic ovary syndrome (PCOS) and 147 control women. The 6/6 genotype was defined with significant difference of CYP11a polymorphism between women with PCOS and control women, and associated with greater BMI in PCOS patients, suggesting a certain role of the six-repeat allele variant in the pathogenesis of Chinese women with PCOS. [Copyright &y& Elsevier]

The polymorphisms of the peroxisome proliferator–activated receptor-γ (Pro12Ala) and its coactivator-1 (Gly482Ser) genes were investigated among 201 Chinese Han women with polycystic ovary syndrome (PCOS) and among 147 regularly cycling women as control subjects. We did not find statistically significant differences with peroxisome proliferator-activated receptor-γ2 Pro12Ala and peroxisome proliferator-activated receptor-gamma-1α Gly482Ser polymorphism distributions between Chinese women with PCOS and controls, or with body mass index and reproductive hormones among various genotypic groups of PCOS, suggesting that these genetic mutants did not have an effect on the susceptibility to PCOS. [Copyright &y& Elsevier]

The preparation of thin metal-organic framework (MOF) membranes by seeded secondary growth method is still a challenge. In this study, relatively thin ZIF-8 membranes with high gas separation performance on alumina hollow fibers are prepared in autoclaves with thick-walled Teflon-liners by the seeded secondary growth method under the modulation of sodium formate. The ZIF-8 membrane thickness can be greatly decreased and the cracks in the membrane layer can be avoided by using thick-walled Teflon-liner (e.g., 7.5 mm) during secondary growth mainly due to the slow heating and cooling of the synthesis solution, which can control the nucleation rate and growth rate of crystals, leading to an appropriate membrane formation rate. A certain amount of sodium formate can introduce ZnO particles in the seed layer to improve the formation of dense ZIF-8 membrane layer and control the growth rate of membrane layer. The suitable amount of sodium formate and thick-walled Teflon-liner are crucial in ensuring the well-intergrowth of relatively thin ZIF-8 membranes. Owing to reduced grain boundary defects, the prepared ZIF-8 membranes show an ideal H 2 /N 2 separation selectivity of 30.9 ± 1.8, which is at least twice the highest value reported in the literature under similar separation conditions. Image 1 • Thin and dense ZIF-8 membranes obtained in a thick-walled Teflon-liner. • Thin and dense ZIF-8 membranes obtained by slow-heating up. • Appropriate sodium formate content, thickness of liner and seeds are important. • The highest H 2 /N 2 separation selectivity for ZIF-8 membranes reported so far. [ABSTRACT FROM AUTHOR]

In this paper, a series of terminal alloys were first prepared, undergoing microstructure and composition characterizations through a combination of X-ray diffraction (XRD), scanning electron microscopy (SEM), and electron probe microanalysis (EPMA) techniques. Subsequent diffusion couple experiments were conducted to acquire initial concentration profiles in fcc Co-Mn-Fe and Co-Mn-Ni alloys. By leveraging experimental composition profiles from 12 groups of diffusion couples measured using EPMA, alongside the reported thermodynamic data, atomic mobility parameters within the fcc phase of the two ternary systems were accurately determined using HitDIC software. Employing the resulting kinetic databases, a comprehensive set of simulated data, including composition profiles and diffusion paths, was generated for all diffusion couples, demonstrating strong alignment with corresponding experimental results. Moreover, interdiffusivities spanning a wider composition range within the fcc phase of Co-Mn-Fe and Co-Mn-Ni systems were computed at different temperatures, shedding light on the diffusion behavior of alloy components in response to temperature and concentration fluctuations. Finally, drawing from the reported thermodynamic data and the currently matched atomic mobility parameters, overviews of the intricate relationships among diffusion-related properties and configurational entropy indicate that the endeavor to develop comprehensive thermodynamic and kinetic databases is essential for tailoring High-Entropy Alloys. • 12 groups of fcc single-phase Co-Mn-X (X = Fe, Ni) diffusion couples were prepared. • Self-consistent kinetic descriptions for target alloys were accurately determined. • High-throughput determination is achieved using the numerical inverse method. • Accuracy of the evaluated kinetic descriptions was comprehensively proved. [ABSTRACT FROM AUTHOR]

Background. Ewing's sarcoma (ES) is the most common malignant primary bone tumor in children and adolescents. This study is aimed at developing new prognostic markers and building a microRNA-mRNA network in the development of ES. Method. GSE80201 and GSE39262 were downloaded from the Gene Expression Omnibus (GEO) database. Bioinformatics analysis was used to download and process data. The coexpression of differentially expressed microRNAs (DEMs) and genes (DEGs) was selected by using R software. The FunRich database was utilized to perform cellular component (CC), molecular function (MF), and biological process (BP) enrichment analysis. Cytoscape and ClueGO were used to perform Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and construct the mRNA-microRNA network. The Kaplan-Meier Plotter was used to perform prognosis analysis between the expression level of genes we selected and overall survival (OS) of patients with ES. Univariate analysis and multivariate analysis were carried out to research the prognostic value of identified mRNA expression in ES according to TCGA database. Results. By using bioinformatics analysis, 10 DEMs and 5 target mRNAs were identified. Based on the KmPlot software, COL1A2, COL3A1, and TGFBI were significantly related to the OS of patients with ES. High COL3A1 mRNA expression was correlated with distant metastasis, margin status, and poor overall survival of ES. Besides, multivariate analysis indicated that COL3A1 was an independent risk factor for ES patients. Conclusions. In conclusion, our results suggest that COL3A1 and its related molecules may be a potential diagnostic and prognostic biomarker for patients with ES. [ABSTRACT FROM AUTHOR]

Reliable diffusivities and atomic mobilities of fcc Co–Mn–Cr alloys are the important keystones for establishing the accurate diffusion database for CoCrFeMnNi high-entropy alloys and other relevant alloys, but they are still missing in the literature. In this paper, diffusion couple experiments together with Hi gh- t hroughput D etermination of I nterdiffusion C oefficients (HitDIC) software were employed to efficiently obtain diffusion descriptions of fcc Co–Mn–Cr alloys. Six diffusion couples were prepared and examined to provide the prerequisite composition profiles. Feature selection and regularization techniques in HitDIC software were adopted to extract the corresponding interdiffusion coefficients and atomic mobilities. A reliable set of diffusion descriptions of the fcc Co–Mn–Cr alloys were therefore obtained and verified. Investigations of the underlying composition- and temperature-dependent diffusion behaviors were enabled and demonstrated. [ABSTRACT FROM AUTHOR]

Sexual hormone binding globulin (SHBG) is associated with the endocrine and reproductive systems. We aimed to investigate the role of SHBG in the reproductive process. Therefore, we conducted a secondary analysis of the PCOSAct (Polycystic Ovary Syndrome and Acupuncture Clinical Trial) study, which involved 21 sites in China and a total of 1000 women with PCOS. Out of these, 954 women with SHBG were included in the analysis. Through multivariate analysis of ovulation predictors, we found that age, BMI, estradiol, testosterone, and SHBG all showed a positive predictive value for ovulation (p = 0.0211, 0.0011, 0.0211, 0.0029, 0.0434, respectively). However, the LH to FSH ratio had a negative predictive value (p = 0.0539). Higher quartiles of SHBG were associated with a higher rate of ovulation, and per quartile increased was statistically significant (HR = 1.138, 95%CI [1.054,1.229]). The association remained significant even after adjusting for testosterone (HR = 1.263, 95%CI [1.059, 1.507]). On the other hand, quartiles of testosterone and estradiol did not exhibit any significant tendency toward ovulation. SHBG demonstrated predictive ability for ovulation, conception, pregnancy, and live birth (p < 0.05), and this correlation remained significant after adjusting intervention. Kaplan-Meier curves illustrated that increased levels of SHBG were a factor in high rates of ovulation, conception, and pregnancy. In comparison to other sexual hormones, a higher baseline level of SHBG was related to increased ovulation. [ABSTRACT FROM AUTHOR]

In vitro fertilization-embryo transfer (IVF-ET) is a very common treatment for couples with infertility. However, IVF-ET still has a limited success rate with high costs. Chinese herbal medicines (CHM) have been used as complementary treatments for infertility to improve the reproductive outcomes during different stages of the IVF-ET cycle. This review provides an up to date evidence on CHM treatments. We summarize the treatment protocols based on the stages of IVF-ET cycle and discuss its clinical applications in IVF-ET treatment. The possible underlying mechanisms of CHM include improving ovarian function, promoting endometrial receptivity, regulating immune function, inhibiting oxidation, and reducing mental stress and discomfort during treatment. This review aims to provide information and guidance on the potential clinical applications of CHM as an adjuvant therapy during IVF-ET treatment. [ABSTRACT FROM AUTHOR]

Clinical trials in infertility choose from a variety of outcomes including change in some surrogate marker of gamete quality to healthy live birth. Incomplete reporting of outcomes makes it difficult to compare studies and to determine the clinical impact of infertility treatments. In this Views and Reviews, we explore the merits of collecting various outcomes of interest in infertility trials from the vantage point of infertility specialists, an obstetrician, and a pediatrician. These articles support more complete reporting of maternal, paternal, fetal, and infant outcomes from infertility trials to improve patient care and ultimately public health. [Copyright &y& Elsevier]

Background: Excessive production of androgen drives oxidative stress (OS) and inflammasome activation in ovarian granulosa cells (GCs). Therefore, the induced follicular developmental disorder is the major cause of infertility in women with polycystic ovary syndrome (PCOS). Exercise-induced upregulation of irisin is capable of regulating metabolism by reducing OS and inflammation. Exercise has been shown to alleviate a range of PCOS symptoms, including maintaining a normal menstrual cycle, in several clinical trials. Methods: Female Sprague–Dawley (SD) rats and primary ovarian cells were treated with two different androgens, dehydroepiandrosterone (DHEA) and dihydrotestosterone (DHT), to simulate a hyperandrogenic environment, followed by eight weeks of exercise training and irisin intervention. The levels of reactive oxygen species (ROS), tissue inflammation and fibrosis were examined using hematoxylin and eosin (H&E) staining, western blot, quantitative real-time PCR (qRT-PCR), dichlorofluorescein diacetate (DCF-DA) probe detection, immunofluorescence staining, immunohistochemistry, and Sirius red staining. Results: Exercise for eight weeks improved polycystic ovarian morphology and decreased the levels of inflammation, OS, and fibrosis in PCOS rats. Hyperandrogen increased ROS production in ovarian cells by inducing endoplasmic reticulum stress (ERS) and activating the inositol-requiring enzyme 1α (IRE1α)-thioredoxin-interacting protein (TXNIP)/ROS-NOD-like receptor family pyrin domain containing 3 (NLRP3) signaling pathway, further enhancing the levels of inflammation. Irisin suppressed the expression of IRE1α and its downstream targets, thus improving the ovarian dysfunction of PCOS rats induced by hyperandrogen. Conclusion: Exercise can alleviate various phenotypes of PCOS rats induced by DHEA, and its therapeutic effect may be mediated by secreting beneficial myokines. IRE1α may be an important target of irisin for reducing OS and inflammation, thereby improving ovarian fibrosis. [ABSTRACT FROM AUTHOR]

Introduction: Autoimmune encephalitis (AE) is a heterogeneous group of inflammatory central nervous system disorders caused by a misdirected immune response against self‐antigens expressed in the central nervous system. The thymus is a central organ in the immune system and thymic tumors are thought to be possible initiators of many neurological disorders. Recently, there is growing evidence that thymomas are associated with autoimmune encephalitis. Aims: Our study initially explored the characteristics of patients with autoimmune encephalitis combined with thymoma. Methods: We used patient data from January 1, 2011 to October 1, 2021 from the PubMed, Web of Science, Ovid, and CNKI platforms to analyze overall demographics, frequency of symptoms and associations, and treatment prognosis outcomes. Results: A total of 68 patients were included. There were 39 female cases (57.4%). The mean age was 50 years (IQR 40–66 years). All had acute and subacute onset. The clinical manifestations were mostly cognitive changes (70.6%), mental disorders (57.4%), and epilepsy (50.0%). The most common neuronal antibody was alpha‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA). Magnetic resonance imaging (MRI) abnormalities were present in 81.0% of patients, mostly in the hippocampus, temporal lobe, and some in cortical and subcortical areas. Abnormalities in the electroencephalogram (EEG) in 69.8% of patients. Treatment involved immunotherapy and thymoma treatment, with 79.7% of patients improving after treatment. While 20.3% of patients had a poor prognosis. Further, 14.8% of patients relapsed. Mental disorders, autonomic dysfunction, sleep disturbances, anti‐Ma2, and thymoma untreated were more frequent in patients with poor prognosis. Conclusion: Thymoma‐associated autoimmune encephalitis is a unique disease entity. Long‐term follow‐up of chest CT findings is recommended for patients with autoimmune encephalitis. [ABSTRACT FROM AUTHOR]

Background: Exosome is crucial mediator and play an important role in tumor angiogenesis. Tip cell formation is a prerequisite for persistent tumor angiogenesis which causes tumor metastasis. However, the functions and underlying mechanisms of tumor cell-derived exosomes in angiogenesis and tip cell formation remain less understood. Methods: Exosomes derived from serum of colorectal cancer (CRC) patients with metastasis/non-metastasis and CRC cells were isolated by ultracentrifugation. CircRNAs in these exosomes were analyzed by circRNA microarray. Then, exosomal circTUBGCP4 was identified and verified by quantitative real-time PCR (qRT–PCR) and in situ hybridization (ISH). Loss- and gain-of-function assays were performed to explore the effect of exosomal circTUBGCP4 on vascular endothelial cell tipping and colorectal cancer metastasis in vitro and in vivo. Mechanically, bioinformatics analysis, biotin-labeled circTUBGCP4/ miR-146b-3p RNA pulldown, RNA immunoprecipitation (RIP), and luciferase reporter assay were used to confirm the interaction among circTUBGCP4, miR-146b-3p, and PDK2. Results: Here, we showed that exosomes derived from CRC cells enhanced vascular endothelial cell migration and tube formation via inducing filopodia formation and endothelial cell tipping. We further screened the upregulated circTUBGCP4 in serum of CRC patients with metastasis compared to non-metastasis. Silencing circTUBGCP4 expression in CRC cell-derived exosomes (CRC-CDEs) inhibited endothelial cell migration, tube formation, tip cell formation, and CRC metastasis. Overexpression of circTUBGCP4 had opposite results in vitro and in vivo. Mechanically, circTUBGCP4 upregulated PDK2 to activate Akt signaling pathway by sponging miR-146b-3p. Moreover, we found that miR-146b-3p could be a key regulator for vascular endothelial cell dysfunction. Exosomal circTUBGCP4 promoted tip cell formation and activated the Akt signaling pathway by inhibiting miR-146b-3p. Conclusions: Our results suggest that colorectal cancer cells generate exosomal circTUBGCP4, which causes vascular endothelial cell tipping to promote angiogenesis and tumor metastasis by activating Akt signaling pathway. [ABSTRACT FROM AUTHOR]

Ovarian cancer is one of the most lethal gynecological malignancies, because of metastatic dissemination with poor late clinical therapy. Maggots have been used in traditional Chinese medicine, where they are also known as 'Wu Gu Chong'. Previous studies have indicated that maggot extract (ME) was beneficial for the treatment of gastric cancer when combined with other drugs, but the effect on anti-ovarian cancer and the underlying mechanism remains unclear. The aim of this study was to investigate the effects of ME on suppressing the proliferation and migration of ovarian cancer cells, and to clarify the underlying mechanism. In this research, Cell Counting Kit-8 (CCK-8), colony formation assay, and luciferase-positive cell quantification assay were employed to identify the inhibitory effects of ME on cell proliferation. Then, the pro-apoptosis and anti-metastasis effects of ME were explored by Western blot, dual annexin V-fluorescein isothiocyanate/propidium iodide (FITC/PI) assay, immunofluorescent staining, and wound-healing assay. We further established a xenograft model by subcutaneously or intraperitoneally injecting BALB/c nude mice with SKOV3 cells stably expressing luciferase, and the mice were treated with ME. The results showed that ME therapy effectively restrained the growth and metastasis of ovarian tumors in vivo. Furthermore, the mRNA levels of cancer factors including heat shock protein 90 alpha family class B member 1 (HSP90AB1), MYC, and insulin like growth factor 1 receptor (IGF1R) were analyzed by quantitative real-time PCR assay to explore the possible antitumor mechanisms of ME. Next, HSP90 ATPase activity was inhibited by geldanamycin in A2780, and the cell viability was shown to be dramatically reduced, decreasing further with the combination of ME and cisplatin. In turn, HSP90AB1 overexpression effectively inhibited the effect of ME in suppressing capability for cell viability and migration. In addition, HSP90AB1 overexpression limited the ability of ME to inhibit expression of MYC and IGF1R, while the opposite effect was observed for expression of pro-apoptosis protein caspase3 and BAX. Therefore, this study confirmed the potential roles and mechanisms of ME in inhibiting the growth and metastasis of ovarian tumors and promoting apoptosis of ovarian cancer cells by inhibiting overexpression of HSP90AB1. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a common endocrine disorder among women. Moderate aerobic exercise intervention is considered an initial treatment strategy for managing PCOS. Brain-derived neurotrophic factor (BDNF) is an important molecular mediator and a beneficial response to exercise. We aimed to investigate the expression pattern and underlying molecular mechanisms of this neurotrophic factor during follicle development in ovarian tissues. The PCOS model was established by subcutaneous injection of 60 mg/kg dehydroepiandrosterone (DHEA) into the neck of Sprague Dawley rats for 35 consecutive days. PCOS rats then received aerobic exercise for 8 weeks. Body/ovarian weight and peripheral serum hormone levels were observed. Immunohistochemistry combined with Western blot analysis and fluorescence quantitative polymerase chain reaction were used to detect the changes in BDNF-TrkB/p75NTR pathway, apoptosis, and inflammatory factors. We show that moderate aerobic exercise not only reverses the PCOS phenotype but also activates the BDNF-TrkB pathway and initiates downstream targets. p-TrkB upregulates and phosphorylates phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) to inhibit apoptosis. In addition, aerobic exercise therapy reduces the high expression of p75NTR in the ovarian tissue of PCOS rats and initiates the anti-apoptotic effect from the downstream pathway of NF-κB/JNK. Our in vitro results state that treatment with BDNF ameliorated dihydrotestosterone (DHT)-induced granulosa cells (GCs) apoptosis by provoking p-TrkB activation and upregulating the PI3K/AKT pathway. The present study suggests that moderate aerobic exercise regulates follicular dysfunction in PCOS-like rats. One possible mechanism is to initiate the BDNF-mediated anti-apoptotic signaling pathway. [ABSTRACT FROM AUTHOR]

Objective: To systematically review the clinical efficacy and safety of Chinese herbal medicine (CHM) with and without Western medicine (WM) for different severity of COVID-19. Methods: CNKI, PubMed, Wanfang Database, ClinicalTrails.gov, Embase, ChiCTR and ICTRP were searched from 01 Jan, 2020 to 30 Jun, 2021. Two authors independently assessed all the randomized clinical trials (RCTs) for trial inclusion, data extraction and quality assessment. Meta-analysis was conducted using Review Manager software (RevMan 5.4.1). Evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Primary outcomes included total effectiveness rate. Secondary outcomes included improvements in symptom improvement and total adverse event rate. Different severity of COVID-19 patients was assessed in subgroup analysis. This study was registered with INPLASY, INPLASY202210072. Results: 22 high quality RCTs involving 1789 participants were included. There were no trial used CHM alone nor compare placebo or no treatment. Compared with WM, combined CHM and WM (CHM-WM) treatment showed higher total effectiveness rate, lower symptom scores of fever, cough, fatigue, dry throat and pharyngalgia, shorter mean time to viral conversion, better Computerized Tomography (CT) image and blood results, fewer total adverse events and worse conditions (P < 0.05). Subgroup analysis showed that the total effectiveness rate of combined CHM-WM group was significantly higher than WM group, especially for mild and moderate patients. No significant differences in mortality and adverse events were found between combined CHM-WM and WM treatment. No serious adverse events and long-term outcomes were reported. Conclusion: Current evidence supported the therapeutic effects and safety of combined CHM-WM treatment on COVID-19, especially for patients with mild and moderate symptoms. Long-term effects of therapy are worthy in further study. [ABSTRACT FROM AUTHOR]

This work delivers a report on development of atomic mobility description with quantified uncertainties directly from concentration profiles via the Markov chain Monte Carlo algorithm as implemented in HitDIC software, which was demonstrated in fcc Cu–Ni–Sn ternary system. Different from the traditional mobility evaluation, the present new strategy started from the collection and review of all the concentration profiles available in the literature. Based on the collected concentration profiles, the atomic mobility descriptions and the corresponding quantified uncertainties in fcc Cu–Ni–Sn ternary and its sub-binary systems were directly evaluated. The reliability of the obtained mobility descriptions was firstly validated by the good agreement between the simulated and measured composition profiles, as well as by the calculated and reported inter-, tracer and intrinsic diffusivities. The fit of diffusion quantities to the experimental results as predicted by the present mobilities was also found to be generally better than previous traditional assessments, further verifying the accuracy of the present mobility descriptions. Moreover, the estimated mobility uncertainties suggest that the stability and reliability of mobility descriptions highly depend on the quantity and quality of the input concentration profiles. The successful demonstration of the present work indicates that the high-quality atomic mobility database in various alloys can be efficiently established by combining the HitDIC software and reliable concentration profiles. [ABSTRACT FROM AUTHOR]

In traditional Chinese medicine, polycystic ovary syndrome (PCOS) is considered an anovulation disorder related to ovarian insulin resistance. The three phenotypes of PCOS, according to the Rotterdam criteria, are differently steroidogenic but similarly insulin resistant, suggesting a similar involvement of insulin resistance/hyperinsulinemia in different compartments of the PCOS ovary, namely, overactive theca and/or granulosa cells. [Copyright &y& Elsevier]

Objective: To investigate whether insulin resistance (IR) within theca cells may directly contribute to their hyperandrogenism, a heritable trait of polycystic ovary syndrome (PCOS).Design: In vitro cell model.Setting: University-affiliated laboratory.Animal(s): Porcine ovaries.Intervention(s): Ovarian theca cells from porcine follicles were isolated and cultured. Insulin resistance was induced in theca cells without (Con) or with dexamethasone (Dex); cells were further treated by troglitazone (Tro) and metformin (Met) in IR cells or by vehicle only in IR and Con cells.Main Outcome Measure(s): Medium glucose and T levels; reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot for insulin signal molecules and androgenic enzyme.Result(s): As compared with Con cells, Dex-treated cells had significantly lower [(3)H]-glucose uptake (565 +/- 58 cpm/10(6) vs. 1077 +/- 78 cpm/10(6)) but higher medium glucose levels (16.31 +/- 0.39 nmol/L vs. 10.62 +/- 1.02 nmol/L) and had approximately twofold T levels (0.82 +/- 0.20 microg/L vs. 0.38+/-0.08 microg/L). Troglitazone and Met significantly reduced the medium glucose and testosterone concentrations to levels comparable to those in Con cells. The RT-PCR and Western blot showed that the two sensitizers in different ways reversed the altered messenger RNA and protein expression of insulin receptor substrate-1, glucose transporter-4, peroxisome proliferator-activated receptor-gamma, and 17 alpha-hydroxylase in Dex-induced IR cells.Conclusion(s): Insulin resistance induced by Dex could directly exaggerate androgenic potential within theca cells, suggesting the possible involvement of this ovarian metabolic phenotype in PCOS hyperandrogenism. [ABSTRACT FROM AUTHOR]

Zeolite membranes are broadly applied in separation, catalysis, and sensor, yet challenges remain in the preparation process. The design of support is an important component to simplify the synthesis protocol and improve the repeatability. Herein, we present a facile and universal strategy to fabricate high-performance zeolite membranes via engineering the skeleton of hollow fiber supports, on which a variety of high-performance zeolite membranes (e.g., MFI, LTA and FAU) can be obtained just by in-situ crystallization without any modification. The "reactive" support is fabricated by implanting zeolite crystals (e.g., NaA) in the precursor of porous ceramic alumina support. Being dissolved under alkaline condition of the synthesis solution, the zeolite calcination transformant (e.g., NaA-Cal) produced in the support during sintering process can effectively form nucleation sites on the support surface, and continuously provide active species to ensure the continuity of the membrane. This study contributes new insights into the importance of supports for high-performance zeolite membranes. Meanwhile, the synthetic methodology is expected to expand the preparation method of zeolite membranes and promote the large-scale application of zeolite membranes. [Display omitted] • Implanting zeolite crystals into the ceramic slurry for preparation of versatile supports. • A variety of high-performance zeolite membranes can be obtained on the support. • No modification or repeated synthesis is needed using the versatile support. [ABSTRACT FROM AUTHOR]

In this study, we show that during normal rat pregnancy, there is a gestational stage-dependent decrease in androgen receptor (AR) abundance in the gravid uterus and that this is correlated with the differential expression of endometrial receptivity and decidualization genes during early and mid-gestation. In contrast, exposure to 5α-dihydrotestosterone (DHT) and insulin (INS) or DHT alone significantly increased AR protein levels in the uterus in association with the aberrant expression of endometrial receptivity and decidualization genes, as well as disrupted implantation. Next, we assessed the functional relevance of the androgen-AR axis in the uterus for reproductive outcomes by treating normal pregnant rats and pregnant rats exposed to DHT and INS with the anti-androgen flutamide. We found that AR blockage using flutamide largely attenuated the DHT and INS-induced maternal endocrine, metabolic, and fertility impairments in pregnant rats in association with suppressed induction of uterine AR protein abundance and androgen-regulated response protein and normalized expression of several endometrial receptivity and decidualization genes. Further, blockade of AR normalized the expression of the mitochondrial biogenesis marker Nrf1 and the mitochondrial functional proteins Complexes I and II, VDAC, and PHB1. However, flutamide treatment did not rescue the compromised mitochondrial structure resulting from co-exposure to DHT and INS. These results demonstrate that functional AR protein is an important factor for gravid uterine function. Impairments in the uterine androgen-AR axis are accompanied by decreased endometrial receptivity, decidualization, and mitochondrial dysfunction, which might contribute to abnormal implantation in pregnant PCOS patients with compromised pregnancy outcomes and subfertility. Key messages: The proper regulation of uterine androgen receptor (AR) contributes to a normal pregnancy process, whereas the aberrant regulation of uterine AR might be linked to polycystic ovary syndrome (PCOS)-induced pregnancy-related complications. In the current study, we found that during normal rat pregnancy there is a stage-dependent decrease in AR abundance in the gravid uterus and that this is correlated with the differential expression of the endometrial receptivity and decidualization genes Spp1, Prl, Igfbp1, and Hbegf. Pregnant rats exposed to 5α-dihydrotestosterone (DHT) and insulin (INS) or to DHT alone show elevated uterine AR protein abundance and implantation failure related to the aberrant expression of genes involved in endometrial receptivity and decidualization in early to mid-gestation. Treatment with the anti-androgen flutamide, starting from pre-implantation, effectively prevents DHT + INS-induced defects in endometrial receptivity and decidualization gene expression, restores uterine mitochondrial homeostasis, and increases the pregnancy rate and the numbers of viable fetuses. This study adds to our understanding of the mechanisms underlying poor pregnancy outcomes in PCOS patients and the possible therapeutic use of anti-androgens, including flutamide, after spontaneous conception. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is one of the most common malignant tumours. The recurrence and metastasis of CRC seriously affect the survival rate of patients. Angiogenesis is an extremely important cause of tumour growth and metastasis. Circular RNAs (circRNAs) have been emerged as vital regulators for tumour progression. However, the regulatory role, clinical significance and underlying mechanisms still remain largely unknown. Methods: High-throughput sequencing was used to analyse differential circRNAs expression in tumour and non-tumour tissues of CRC. In situ hybridization (ISH) and qRT-PCR were used to determine the level of circ3823 in CRC tissues and serum samples. Then, functional experiments in vitro and in vivo were performed to investigate the effects of circ3823 on tumour growth, metastasis and angiogenesis in CRC. Sanger sequencing, RNase R and Actinomycin D assay were used to verify the ring structure of circ3823. Mechanistically, dual luciferase reporter assay, fluorescent in situ hybridization (FISH), RNA immunoprecipitation (RIP) and RNA pull-down experiments were performed to confirm the underlying mechanisms of circ3823. Results: Circ3823 was evidently highly expressed in CRC and high circ3823 expression predicted a worse prognosis of CRC patients. Receiver operating characteristic curves (ROCs) indicated that the expression of circ3823 in serum showed high sensitivity and specificity for detecting CRC which means circ3823 have the potential to be used as diagnostic biomarkers. Functional experiments in vitro and in vivo indicated that circ3823 promote CRC cell proliferation, metastasis and angiogenesis. Mechanism analysis showed that circ3823 act as a competing endogenous RNA of miR-30c-5p to relieve the repressive effect of miR-30c-5p on its target TCF7 which upregulates MYC and CCND1, and finally facilitates CRC progression. In addition, we found that N6-methyladenosine (m6A) modification exists on circ3823. And the m6A modification is involved in regulating the degradation of circ3823. Conclusions: Our findings suggest that circ3823 promotes CRC growth, metastasis and angiogenesis through circ3823/miR-30c-5p/TCF7 axis and it may serve as a new diagnostic marker or target for treatment of CRC patients. In addition, m6A modification is involved in regulating the degradation of circ3823. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a frequent gynecological female endocrinopathy, characterized by chronic anovulation, hyperandrogenism, and insulin resistance (IR). Menstrual disorders are one of the main clinical manifestations of PCOS. Other symptoms include hirsutism and/acne. At present, the treatment of PCOS with irregular menstruation is mainly based on oral contraceptives, but there are some side effects and adverse reactions. In recent years, more and more attention has been paid to the complementary and alternative medicine (CAM), which has been widely used in clinical practice. Modern Western medicine is called "conventional medicine" or "orthodox medicine," and the complementary and alternative medicine is called "unconventional medicine" or "unorthodox medicine." CAM includes traditional medicine and folk therapy around the world. Around 65–80% of world health management business is classified into traditional medicine by the World Health Organization, which is used as alternative medicine in Western countries. In our country, Chinese medicine, acupuncture, and other therapies are commonly used due to their significant efficacy and higher safety. Therefore, this review aims to summarize and evaluate the mechanisms and the effect of current complementary replacement therapy in the treatment of menstrual disorders caused by PCOS, so as to provide guidance for the following basic and clinical research. [ABSTRACT FROM AUTHOR]

The hydrothermal synthesis for the fabrication of zeolite coatings is the most effective route and has been extensively studied, in which a large amount of water is indispensable to ensure efficient transport of nutrition. The disposal of waste solvent and chemicals remains a big challenge in practice and an alternative route is highly desired. Herein, we present an unprecedented solid-conversion secondary growth route for the fabrication of corrosion-resistant MFI-type zeolite coatings by mixing, grinding, and heating the mixture of silica source (Na 2 SiO 3 ·9H 2 O and SiO 2), template (TPABr) and acidity regulator (NH 4 Cl) without addition of water. The ZSM-5 zeolite seeded aluminum alloy 1060 plates were prepared by spray-coating method where water glass as a binder between seed and substrate was used to increase the adhesion of seeds to the substrate. The continuity of the coatings was investigated by manipulating the molar composition of synthesis mixture and the optimized molar composition is 1.0Na 2 SiO 3 ·9H 2 O: 1.19SiO 2 : 0.58TPABr: 1.82NH 4 Cl. The corrosion protection performance of MFI-type zeolite coatings on aluminum alloy plates was evaluated by a direct current polarization technique. The excellent corrosion-resistant was demonstrated in severely corrosive medium including in 0.5 M H 2 SO 4 aqueous solution and 0.5 M NaCl aqueous solution, which is comparable to the performance of zeolite coatings synthesized by hydrothermal synthesis. The features are also briefly discussed, which make this route highly attractive from a good perspective. Image 1 ● The synthesis of MFI-type zeolite coatings by solid-conversion secondary growth route. ● Spray-coating was introduced to produce a continuous seed layer. ● Significant effect of the composition of synthesis mixture in solid-conversion method. ● MFI-type zeolite coatings are corrosion-resistant in severely corrosive medium. [ABSTRACT FROM AUTHOR]

This work sought to evaluate the effects of three androgen indexes of free testosterone (FT), total testosterone (TT), and free-androgen index (FAI) on clinical phenotype, endocrine metabolic disorders, and fertility outcomes in women with polycystic ovary syndrome. The data in this study came from a large, multicenter, randomized double-blind controlled clinical trial involving 1000 infertile PCOS patients. Baseline phenotypic, endocrine, and metabolic parameters and fertility outcomes undergoing ovulation induction were collected. FAI is superior to FT, and FT is superior to TT in terms of their correlation with anthropometric parameters and metabolic profile. FT and TT were significantly positively correlated with LH/FSH. FAI and FT were significantly correlated with the incidence of metabolic syndrome. FAI, FT, and TT were significantly positively correlated with polycystic ovary morphology and menstrual period. FAI was significantly related ovulations per cycle, pregnancy, conception, and live birth rates. After adjusting for age, the increased FT level was significantly related to the decreased rates of ovulations per cycle, conception, and pregnancy. FAI is superior to FT and FT is superior to TT in terms of their correlation with phenotypic and metabolic parameters in PCOS patients. FAI and FT are important factors related to the fertility outcomes of infertile PCOS patients. Clinical trial registration number: NCT01573858. [ABSTRACT FROM AUTHOR]

In this paper, 6 Cu-Al-Sn ternary and 8 Cu-Ni-Al-Sn quaternary solid diffusion couples within single fcc phase from 1023 K to 1173 K were fabricated. Employing the measured concentration profiles and interdiffusion fluxes, the atomic mobility parameters and interdiffusion coefficients in Cu-Al-Sn and Cu-Ni-Al-Sn systems were high-throughput evaluated using the numerical inverse method. The simulated composition distributions and interdiffusion fluxes in all the diffusion couples are consistent with the measured ones confirming the reliability of the atomic mobilities. The Matano-Kirkaldy method was also used to validate the reliability of the accuracy of the determined interdiffusion matrices. The 3D diagrams of main interdiffusivities in the Cu-Al-Sn and Cu-Ni-Al-Sn systems in the investigated ranges of composition and temperature were established to analyze the effects of components on the diffusivities. In the Cu-Al-Sn system, there is an increase in D ˜ A l A l C u with an increase in x Al , while D ˜ S n S n C u increases with increasing x Sn but decreases with the addition of Al. Additionally, the introduction of Ni results in a decrease in all the main interdiffusivities ( D ˜ N i N i C u , D ˜ A l A l C u and D ˜ S n S n C u ) in the Cu-Ni-Al-Sn system. [ABSTRACT FROM AUTHOR]

Aim: This work sought to evaluate the correlation between the five domains of the Polycystic Ovary Syndrome Questionnaire (PCOSQ) and anxiety and depression scales and the clinical phenotype and fertility outcomes in infertile polycystic ovary syndrome (PCOS) patients and to determine the effect of quality of life (QOL) on the clinical, biochemical and fertility disorders in these patients. Methods: The data in this study came from a large‐scale hospital‐based cohort survey of infertile PCOS patients across mainland China. A total of 1000 infertile PCOS subjects diagnosed according to the modified Rotterdam criteria ranging in age from 20 to 40 years in 21 sub‐centers (27 hospitals) were enrolled. Baseline anthropometric parameters, endocrine indexes, metabolic panel, QOL questionnaires and the fertility outcomes of ovulation, conception, pregnancy, pregnancy loss and live birth were collected. Results: PCOSQ scores were significantly correlated with most of the baseline parameters. PCOSQ‐weight domain scores of National Institute of Health‐PCOS group were significantly lower compared with non‐National Institute of Health‐PCOS group. The five domains scores of PCOSQ were significantly negatively correlated with the body mass index levels of PCOS patients. The serum testosterone levels (total testosterone, free testosterone and free androgen index) were significantly negatively correlated to the scores for the weight, body hair, infertility and emotion domains of PCOSQ. Scores on the anxiety and depression scales were significantly and positively correlated with luteinizing hormone, luteinizing hormone/follicle‐stimulating hormone levels. In the low‐score group of infertility domain, the rates of conception, pregnancy and live birth decreased significantly. Conclusions: QOL appears to have an impact on the physical symptoms of PCOS, and the emotional stress of infertility affects fertility outcomes. [ABSTRACT FROM AUTHOR]

Insulin resistance on porcine granulosa cells was induced by wortmannin, the phosphatidylinositol-3-kinase inhibitor, and insulin signaling key molecules were investigated including glut4 and mitogen-activated protein kinase. Granulosa insulin resistance decreased glut4 expression but increased mitogen-activated protein kinase, indicating the cross talk between the metabolic and mitogenic pathways of insulin signaling in the ovary. [Copyright &y& Elsevier]

Purpose. To assess the efficacy and safety of berberine on reproductive endocrine and metabolic outcomes in women with polycystic ovary syndrome (PCOS). Methods. PubMed (from 1950), the Cochrane Library, the CNKI (from 1979), the VIP (from 1989), and the Wanfang Data (from 1990) and the reference lists of the retrieved articles were searched for randomized controlled trials in human beings with the search terms including "polycystic ovary syndrome/PCOS" and "berberine/BBR/Huangliansu (in Chinese)/Xiao bojian (in Chinese)" till 30 May 2019. Relevant indicators were collected and the data were analyzed by using RevMan 5.3 software. Results. Eventually, a total of 12 randomized controlled trials were included in this systematic review. Our study suggested that berberine had similar live birth rates compared with placebo or metformin and lower live birth rates (RR: 0.61, 95% CI: 0.44 to 0.82) compared with letrozole. There was a significant difference between berberine and placebo and between berberine and no treatment in terms of decreasing total testosterone and luteinizing hormone to follicle-stimulating hormone (LH/FSH) ratio (8 RCTs, 577 participants, MD: −0.34, 95% CI: −0.47 to −0.20; 3 RCTs, 179 participants, MD: −0.44, 95% CI: −0.68 to −0.21, respectively). Berberine was associated with decreasing total cholesterol (3 RCTs, 201 participants; MD: −0.44, 95% CI: −0.60 to −0.29), waist circumference (3 RCTs, 197 participants, MD: −2.74, 95% CI: −4.55 to −0.93), and waist-to-hip ratio (4 RCTs, 258 participants, MD: −0.04, 95% CI: −0.05 to −0.03) compared with metformin, but not with improved BMI (4 RCTs, 262 participants, MD: −0.03, 95% CI: −0.46 to 0.39). Berberine did not increase the incidence of gastrointestinal adverse events (3 RCTs, 567 participants, RR: 1.01, 95% CI: 0.76 to 1.35) or serious events during pregnancy (RR: 0.98, 95% CI: 0.70 to 1.37) compared with placebo. Conclusion. This review found no solid evidence that berberine could improve live birth or other clinical outcomes in women with PCOS. However, berberine appeared to be more efficacious for improving insulin resistance and dyslipidemia and decreasing androgen levels and LH/FSH ratio in women with PCOS when compared with metformin. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is the most frequent cause of anovulatory infertility. In women with PCOS, effective ovulation induction serves as an important first-line treatment for anovulatory infertility. Individual participant data (IPD) meta-analysis is considered as the gold standard for evidence synthesis which provides accurate assessments of outcomes from primary randomised controlled trials (RCTs) and allows additional analyses for time-to-event outcomes. It also facilitates treatment-covariate interaction analyses and therefore offers an opportunity for personalised medicine.Objective and Rationale: We aimed to evaluate the effectiveness of different ovulation induction agents, in particular letrozole alone and clomiphene citrate (CC) plus metformin, as compared to CC alone, as the first-line choice for ovulation induction in women with PCOS and infertility, and to explore interactions between treatment and participant-level baseline characteristics.Search Methods: We searched electronic databases including MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials up to 20 December 2018. We included RCTs comparing the following interventions with each other or placebo/no treatment in women with PCOS and infertility: CC, metformin, CC plus metformin, letrozole, gonadotrophin and tamoxifen. We excluded studies on treatment-resistant women. The primary outcome was live birth. We contacted the investigators of eligible RCTs to share the IPD and performed IPD meta-analyses. We assessed the risk of bias by using the Cochrane risk of bias tool for RCTs.Outcomes: IPD of 20 RCTs including 3962 women with PCOS were obtained. Six RCTs compared letrozole and CC in 1284 women. Compared with CC, letrozole improved live birth rates (3 RCTs, 1043 women, risk ratio [RR] 1.43, 95% confidence interval [CI] 1.17-1.75, moderate-certainty evidence) and clinical pregnancy rates (6 RCTs, 1284 women, RR 1.45, 95% CI 1.23-1.70, moderate-certainty evidence) and reduced time-to-pregnancy (6 RCTs, 1235 women, hazard ratio [HR] 1.72, 95% CI 1.38-2.15, moderate-certainty evidence). Meta-analyses of effect modifications showed a positive interaction between baseline serum total testosterone levels and treatment effects on live birth (interaction RR 1.29, 95% CI 1.01-1.65). Eight RCTs compared CC plus metformin to CC alone in 1039 women. Compared with CC alone, CC plus metformin might improve clinical pregnancy rates (8 RCTs, 1039 women, RR 1.18, 95% CI 1.00-1.39, low-certainty evidence) and might reduce time-to-pregnancy (7 RCTs, 898 women, HR 1.25, 95% CI 1.00-1.57, low-certainty evidence), but there was insufficient evidence of a difference on live birth rates (5 RCTs, 907 women, RR 1.08, 95% CI 0.87-1.35, low-certainty evidence). Meta-analyses of effect modifications showed a positive interaction between baseline insulin levels and treatment effects on live birth in the comparison between CC plus metformin and CC (interaction RR 1.03, 95% CI 1.01-1.06).Wider Implications: In women with PCOS, letrozole improves live birth and clinical pregnancy rates and reduces time-to-pregnancy compared to CC and therefore can be recommended as the preferred first-line treatment for women with PCOS and infertility. CC plus metformin may increase clinical pregnancy and may reduce time-to-pregnancy compared to CC alone, while there is insufficient evidence of a difference on live birth. Treatment effects of letrozole are influenced by baseline serum levels of total testosterone, while those of CC plus metformin are affected by baseline serum levels of insulin. These interactions between treatments and biomarkers on hyperandrogenaemia and insulin resistance provide further insights into a personalised approach for the management of anovulatory infertility related to PCOS. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the effects of hyperinsulinaemia and insulin resistance (IR) on reproductive and metabolic disorders and fertility in women with polycystic ovary syndrome (PCOS). Design, Setting, Participants and Measurements: This was a multicenter, randomized controlled trial involving a total of 1000 women diagnosed with PCOS according to the modified Rotterdam criteria at 21 sites (27 hospitals). We evaluated the effects of serum insulin levels and HOMA‐IR on parameters and outcomes. The main outcome measures were anthropometric, biometric and ultrasound parameters at baseline and the clinical outcomes of ovulation, conception, pregnancy, live birth and pregnancy loss. Results: The relevant analysis between hyperinsulinaemia and IR and clinical characteristics showed that weight, waist and hip circumference, BMI, waist‐to‐hip ratio, acanthosis nigricans score and menstrual period were significantly correlated with fasting insulin (FIN) and HOMA‐IR. There was no significant correlation between the hirsutism score or acne score with FIN or HOMA‐IR. The relevant analysis between hyperinsulinaemia and IR and circulating sex steroids and gonadotrophins showed that FAI was significantly correlated with FIN and HOMA‐IR (r = 0.240, P < 0.001 and r = 0.191, P < 0.001, respectively). Free testosterone was significantly correlated with FIN after adjusting for the influence of age. LH and LH/FSH were not related to FIN or HOMA‐IR after statistical correction for differences in BMI. The relevant analysis between hyperinsulinaemia and IR and metabolic profile showed that FIN and HOMA‐IR were positively associated with fasting glucose, cholesterol, triglycerides, low‐density lipoprotein, Apo B, and the incidence of metabolic syndrome and were negatively associated with high‐density lipoprotein. The predictive analysis between hyperinsulinaemia and IR with fertility showed that the levels of FIN and HOMA‐IR were related to the fertility outcome (ovulation, pregnancy, conception or live birth) in patients with PCOS. After adjustments for age, total testosterone and free testosterone, increasing serum insulin levels and HOMA‐IR were significantly associated with decreased cycle ovulation, conception, pregnancy and live birth rates. Conclusions: Hyperinsulinaemia and IR are associated with reproductive and metabolic disorders and can predict the fertility outcomes in PCOS patients. [ABSTRACT FROM AUTHOR]

In this paper, 3 fcc binary Ag-In and 3 fcc ternary Ag-Cu-In diffusion couples were firstly prepared. Based on the measured composition-distance profiles, both the traditional Matano method with distribution functions and the numerical inverse method with HitDIC were then utilized to determine the accurate interdiffusion coefficients in fcc Ag-In alloys at 873 K, 973 K, and 1073 K and Ag-Cu-In alloys at 1073 K. The determined interdiffusivities in fcc Ag-In alloys increases as the composition of In increases. The impurity diffusivities of In in fcc Ag extrapolated from the evaluated interdiffusivities based on the Matano method agree well with the tracer experimental data from the literature. As for fcc Ag-Cu-In alloys, the three-dimensional main interdiffusivities planes at 1073 K were constructed over the investigated composition range. The diffusion rate of In is generally faster than that of Cu. Moreover, the main interdiffusivity of In increases with the increment of both In and Cu concentrations, while the main interdiffusivity of Cu increases with In concentration but decreases with Cu concentration. After that, a comprehensively comparative study on the two methods were performed. The interdiffusivities in both the fcc Ag-In and Ag-Cu-In alloys evaluated from the two methods are consistent with each other, indicating that both methods can result in accurate interdiffusivities in binary and ternary alloys. However, as the number of elements increases, the Matano method becomes inconvenient. While for the numerical inverse method with HitDIC, no such limitation exists, and it can be conveniently applied in alloys with any number of components. • 6 fcc binary Ag-In and ternary Ag-Cu-In diffusion couples were prepared. • Matano method and numerical inverse method were used for diffusivity evaluation. • Interdiffusivities evaluated from the two methods are in good agreement. • A comparative study on the features of the two methods was performed. [ABSTRACT FROM AUTHOR]

In this paper, we report the isolation and structure elucidation of 12 known compounds ( B 1-12 b ); eleven compounds ( B 1-11 b ) were isolated for the first time from I L. latifolium i . Part of EtOAc soluble fraction (72.6 g) was subjected to silica gel (200-300 mesh) column chromatography and eluted with an isocratic elution system of dichloromethane-methanol-water (7:3:0.5) to give one fraction (Fr. 1). Subfraction 1-3 was eluted on a Dubhe C18 column and purified on a Megress C18 column to give compounds B 10 b (88.5 mg), B 11 b (4.3 mg), and B 12 b (14.5 mg). After concentration in vacuum, the combined extract (360 g) was suspended in H SB 2 sb O and partitioned with petroleum ether, EtOAc, and I n i -BuOH successively to give dried petroleum ether, EtOAc, I n i -BuOH, and H SB 2 sb O fractions. [Extracted from the article]

What is the association between hyperhomocysteinaemia (HHCY), metabolic syndrome, and reproductive outcomes among women with polycystic ovary syndrome (PCOS). A secondary analysis of PCOSAct with 21 sites in China. A total of 1000 women with PCOS were enrolled; 936 women with baseline homocysteine (HCY) were analysed. Higher HCY was associated with higher body mass index, free testosterone and lower FSH, fasting glucose (P < 0.001; P < 0.001; P = 0.005; P < 0.001) and ovulation rate among all participants (OR 0.59, 95% CI 0.41 to 0.86; OR 0.57, 95% CI 0.39 to 0.83 tertiles 2 and 3 versus tertile 1, respectively). The HHCY group had lower oestradiol and higher free testosterone (P = 0.04; P < 0.001) than the controls. In the metabolic syndrome group, LH, LH–FSH ratio and sex hormone-binding globulin were lowest in the metabolic syndrome group (all P < 0.001). In the HHCY group, ovulation rate decreased and the second or third trimester pregnancy loss rate increased compared with controls (OR 1.678, 95% CI 1.04 to 2.70; OR 0.03, 95% CI 0.00 to 0.42) with treatment adjustment. Compared with the controls, ovulation, conception, pregnancy, second or third trimester pregnancy loss and live birth rates were statistically lower in the metabolic syndrome group after adjusting treatment (OR 1.76, 95% CI 1.15 to 2.70; OR 1.75, 95% CI 1.15 to 2.65; OR 2.09, 95% CI 1.27 to 3.44; OR 0.02, 95% CI 0.00 to 0.33; OR 2.42 95% CI 1.42 to 4.10), and pregnancy, pregnancy loss and live birth rates remained significantly different after adjusting for treatment and sex-hormone factors (OR 1.77, 95% CI 1.05 to 2.99; OR 0.14, 95% CI 0.02 to 0.82; OR 2.02, 95% CI 1.16 to 3.50). In women with PCOS, HHCY contributes to increased pregnancy loss and reduced ovulation, and metabolic syndrome was related to defects in ovulation, conception, pregnancy, pregnancy loss and live birth, indicating that the two conditions lead to defects at various reproductive stages. [ABSTRACT FROM AUTHOR]

The aim of the study is to investigate the molecular mechanism behind androgen reduction in porcine granulosa cells (pGCs) with Salvia miltiorrhiza Bunge extract cryptotanshinone. PGCs were isolated from porcine ovaries and identified. Androgen excess model of the pGCs was induced with the MAPK inhibitor PD98059 and then treated with cryptotanshinone. The testosterone level was measured by radioimmunoassay in the culture media. The protein levels of P-ERK1/2, c-Fos, and CYP17 in the cells were measured by western blot. Cryptotanshinone decreased the concentration of testosterone and the protein level of CYP17 and increased the protein levels of P-ERK1/2 and c-Fos in the androgen excess mode. After the c-Fos gene was silenced by infection with c-Fos shRNA lentivirus, we measured the mRNA expression by quantitative RT-PCR and protein level by western blot of P-ERK1/2, c-Fos, and CYP17. This showed that the mRNA expression and protein level of P-ERK1/2 and c-Fos were significantly reduced in the shRNA–c-Fos group compared to the scrambled group, while those of CYP17 were significantly increased. So we concluded that cryptotanshinone can significantly reduce the androgen excess induced by PD98059 in pGCs. The possible molecular mechanism for this activity is regulating the ERK/c-Fos/CYP17 pathway. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effects of berberine on the menstrual pattern, ovulation rate, hormonal and metabolic profiles in anovulatory Chinese women with polycystic ovary syndrome. Methods: Berberine 0.4 g three times per day was given for four months to 102 anovulatory Chinese women with polycystic ovary syndrome. The menstrual pattern, ovulation rate, hormonal and metabolic profiles were compared before and after the berberine treatment. Ovulation was confirmed by serum progesterone level ≥10ng/ml. Results: A total of 98 of 102 subjects (96.1%) completed the four month treatment, including 69 (70.4%, 69/98) normal weight and 29 (29.6%, 29/98) overweight/obese. Fourteen women (14.3%, 14/98) had regained regular menses after berberine treatment and there was no significant difference between normal weight and overweight/obese groups. The ovulation rate was 25.0% over four months in the whole group, 22.5% in the normal weight group and 31.0% in the overweight/obese group. Sex hormone binding globulin, insulin resistance, total cholesterol, total triglyceride and low-density lipoprotein cholesterol decreased after berberine treatment in the normal weight group only. Conclusions: Our study found that administration of berberine alone may improve the menstrual pattern and ovulation rate in anovulatory Chinese women with polycystic ovary syndrome. Berberine can also decrease sex hormone binding globulin, insulin resistance, total cholesterol, triglycerides and low-density lipoprotein cholesterol in normal weight polycystic ovary syndrome women. Trial Registration: Chictr.org [ABSTRACT FROM AUTHOR]

Aim: To compare the effect of a single session of acupuncture with either low-frequency electrical or manual stimulation on insulin sensitivity and molecular pathways in the insulin-resistant dihydrotestosterone-induced rat polycystic ovary syndrome (PCOS) model. Both stimulations cause activation of afferent nerve fibers. In addition, electrical stimulation causes muscle contractions, enabling us to differentiate changes induced by activation of sensory afferents from contraction-induced changes. Materials and Methods: Control and PCOS rats were divided into no-stimulation, manual-, and electrical stimulation groups and insulin sensitivity was measured by euglycemic hyperinsulinemic clamp. Manually stimulated needles were rotated 180° ten times every 5 min, or low-frequency electrical stimulation was applied to evoke muscle twitches for 45 min. Gene and protein expression were analyzed by real-time PCR and Western blot. Results: The glucose infusion rate (GIR) was lower in PCOS rats than in controls. Electrical stimulation was superior to manual stimulation during treatment but both methods increased GIR to the same extent in the post-stimulation period. Electrical stimulation decreased mRNA expression of Adipor2, Adrb1, Fndc5, Erk2, and Tfam in soleus muscle and increased ovarian Adrb2 and Pdf. Manual stimulation decreased ovarian mRNA expression of Erk2 and Sdnd. Electrical stimulation increased phosphorylated ERK levels in soleus muscle. Conclusions: One acupuncture session with electrical stimulation improves insulin sensitivity and modulates skeletal muscle gene and protein expression more than manual stimulation. Although electrical stimulation is superior to manual in enhancing insulin sensitivity during stimulation, they are equally effective after stimulation indicating that it is activation of sensory afferents rather than muscle contraction per se leading to the observed changes. [ABSTRACT FROM AUTHOR]

Objective To identify aberrantly methylated candidate genes that are involved in the development of polycystic ovary syndrome (PCOS). Design Animal model. Setting University-affiliated laboratory. Animal(s) Sprague-Dawley rats. Intervention(s) The prenatally androgenized (PNA) rat model was established. Pregnant rats were treated with daily SC injections of T propionate during late gestation, and their female offspring were studied as adults. Main Outcome Measure(s) Serum glucose and hormone levels, ovary morphology and cell apoptosis, genome-wide CpG methylation, and expression of caspase-3 protein were measured. Result(s) In the PNA group, the levels of serum glucose, 17-hydroxyprogesterone, and T were significantly higher when compared with the control group. Ovarian morphology showed increased atretic follicles and cystic follicles. Using the MeDIP-chip approach, we identified 528 genes that were hypermethylated in PNA ovaries. Gene ontology analyses revealed that these genes are involved in a variety of reproductive development and biological processes. The methylation enrichments of Bcl2l1 and Scr5a1 observed in the PNA group by MeDIP-quantitative polymerase chain reaction assay were significantly higher than those obtained from the control group. Furthermore, the mRNA level of the Bcl2l1 gene was significantly decreased in the PNA group. The percentage of caspase-3-positive cells in the PNA group was obviously higher compared with the control group, by terminal deoxynucleotidyl transferase dUTP nick end labeling detection as well. Conclusion(s) DNA methylation alteration may be an important factor affecting the genes involved in the pathophysiological processes that result in the phenotype of PCOS. [ABSTRACT FROM AUTHOR]

Background: A large number of infertile couples are choosing Chinese herbal medicine (CHM) as an adjuvant therapy to improve their success when undergoing in vitro fertilization (IVF). There is no systematic review to evaluate the impact of CHM on the IVF outcomes. Objective: To evaluate the effectiveness of CHM with concurrent IVF versus IVF alone on the outcomes of IVF and its safety. Methods: The protocol of this study is registered at PROSPERO. Eligible RCTs searched from 8 databases which compared a combination of CHM and IVF with IVF alone were included. Two authors independently selected studies, extracted data and assessed methodological quality. Meta-analysis of RCTs was conducted if there was non-significant heterogeneity (evaluated by I2 test) among trials. All statistical analysis was performed using RevMan 5.1 software. Results: Twenty trials involving 1721 women were included in the meta-analysis. Three trials were evaluated as having an unclear risk of bias. The remaining trials were evaluated as having a high risk of bias. Combination of CHM and IVF significantly increases clinical pregnancy rates (OR 2.04, 95%CI 1.67 to 2.49, p<0.00001) and ongoing pregnancy rates (OR 1.91, 95%CI 1.17 to 3.10, p = 0.009). Use of CHM after embryo transfer had no better outcome in reducing the rate of ovarian hyper stimulation syndrome (OR 0.39, 95%CI 0.14 to 1.11, p = 0.08). Conclusions: This meta-analysis showed that combination of IVF and CHM used in the included trials improve IVF success, however due to the high risk of bias observed with the trials, the significant differences found with the meta-analysis are unlikely to be accurate. No conclusion could be drawn with respect to the reproductive toxicity of CHM. Further large randomized placebo controlled trials are warranted to confirm these findings before recommending women to take CHM to improve their IVF success. [ABSTRACT FROM AUTHOR]

Study Question: What is the prevalence of polycystic ovary syndrome (PCOS) in Han Chinese women from different communities? Summary Answer: The prevalence of PCOS in Chinese women aged 19-45 years is 5.6%. What Is Known Already: The prevalence of PCOS is reported to range from 5 to 10% but to the best of our knowledge the Han Chinese population has not been studied. Study Design, Size, Duration: A large-scale epidemiological study was carried out between October 2007 and September 2011 in 15 924 Han Chinese women of reproductive age (19-45 years) from the 10 provinces and municipalities in China. Participants/materials, Setting, Methods: A total of 16 886 women from 152 cities and 112 villages were involved in the study. All study participants received a questionnaire and underwent a physical and transvaginal ultrasound examination. Blood samples were collected from a subsample of women (n = 3565) for analysis of metabolic markers and hormones. Based on the Rotterdam PCOS criteria, we assessed hyperandrogenism (H), chronic anovulation (O) and polycystic ovaries (P). Following diagnosis, women with PCOS were assigned to one of four different phenotypes. Finally, the prevalence and related risks of PCOS among Chinese women were estimated based on all the data sources. Main Results and the Role Of Chance: A total of 16 886 women were initially involved in the study and 15 924 eligible participants then completed the study; the overall response rate was 94.3% (15 924/16 886). The prevalence of PCOS in the Chinese community population was 5.6% (894/15 924). Blood samples were analyzed from 833 of these women who were assigned to the four PCOS phenotypes as follows: 19% H + O, 37% H + P, 15% O + P and 29% H + O + P. Comparing the 833 women with PCOS to 2732 women without PCOS indicated that PCOS occurs in younger women (P < 0.05) and these women were prone not only to menstrual problems, hyperandrogenism, PCO and infertility but also metabolic syndrome (MS) and insulin resistance (IR). However, there was no significant difference in the rate of hypertension or hyperlipemia between the two groups. Obese patients with PCOS had a higher rate of MS (16 versus 48%), IR (7 versus 28%), hypertension (8 versus 30%) and hyperlipemia (48 versus 73%) compared with non-obese patients (all P < 0.05), respectively. The rates of metabolic complications in patients with PCOS increased with age. Limitations, Reasons For Caution: Age and ethnic origin contribute to the differing manifestations of PCOS; therefore, sampling is one of the most important issues in epidemiological research into PCOS. Owing to the mobility of the Chinese population, the survey among resident populations caused a certain deviation in the age distribution. Wider Implications Of the Findings: The prevention and treatment of PCOS, particularly in those who are obese, are essential in Chinese women of reproductive age. [ABSTRACT FROM AUTHOR]