Aggf1 Specifies Hemangioblasts at the Top of Regulatory Hierarchy via Npas4l and mTOR-S6K-Emp2-ERK Signaling.

BACKGROUND: Hemangioblasts are mesoderm-derived multipotent stem cells for differentiation of all hematopoietic and endothelial cells in the circulation system. However, the underlying molecular mechanism is poorly understood. METHODS: CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (type II CRISPR RNA-guided endonuclease) editing was used to develop aggf1-/- and emp2-/- knockout zebra fish. Whole-mount in situ hybridization and transgenic Tg(gata1-EGFP [enhanced green fluorescent protein]), Tg(mpx-EGFP), Tg(rag2-DsRed [discosoma sp. red fluorescent protein]), Tg(cd41-EGFP), Tg(kdrl-EGFP), and Tg(aggf1-/-;kdrl-EGFP) zebra fish were used to examine specification of hemangioblasts and hematopoietic stem and progenitor cells (HSPCs), hematopoiesis, and vascular development. Quantitative real-time polymerase chain reaction and Western blot analyses were used for expression analysis of genes and proteins. RESULTS: Knockout of aggf1 impaired specification of hemangioblasts and HSPCs, hematopoiesis, and vascular development in zebra fish. Expression of npas4l/cloche-the presumed earliest marker for hemangioblast specification-was significantly reduced in aggf1-/- embryos and increased by overexpression of aggf1 in embryos. Overexpression of npas4l rescued the impaired specification of hemangioblasts and HSPCs and development of hematopoiesis and intersegmental vessels in aggf1-/- embryos, placing aggf1 upstream of npas4l in hemangioblast specification. To identify the underlying molecular mechanism, we identified emp2 as a key aggf1 downstream gene. Similar to aggf1, emp2 knockout impaired the specification of hemangioblasts and HSPCs, hematopoiesis, and angiogenesis by increasing the phosphorylation of ERK1/2 (extracellular signal-regulated protein kinase 1/2). Mechanistic studies showed that aggf1 knockdown and knockout significantly decreased the phosphorylated levels of mTOR (mammalian target of rapamycin) and p70 S6K (ribosomal protein S6 kinase), resulting in reduced protein synthesis of Emp2 (epithelial membrane protein 2), whereas mTOR activator MHY1485 (4,6-dimorpholino-N-(4-nitrophenyl)-1,3,5-triazin-2-amine) rescued the impaired specification of hemangioblasts and HSPCs and development of hematopoiesis and intersegmental vessels and reduced Emp2 expression induced by aggf1 knockdown. CONCLUSIONS: These results indicate that aggf1 acts at the top of npas4l and becomes the earliest marker during specification of hemangioblasts. Our data identify a novel signaling axis of Aggf1 (angiogenic factor with G-patch and FHA domain 1)-mTOR-S6K-ERK1/2 for specification of hemangioblasts and HSPCs, primitive and definitive hematopoiesis, and vascular development. Our findings provide important insights into specification of hemangioblasts and HSPCs essential for the development of the circulation system.

Effect of marital status on the survival outcomes of cervical cancer: a retrospective cohort study based on SEER database.

BACKGROUND: Cervical cancer is the fourth most common malignant tumor troubling women worldwide. Whether marital status affects the prognosis of cervical cancer is still unclear. Here, we investigate the prognostic value of marital status in patients with cervical cancer based on the seer database. MATERIAL/METHODS: The demographic and clinical data of patients with cervical cancer were extracted from the Surveillance, Epidemiology, and End Results (SEER) database from 1975 to 2017. Patients were divided into two groups (married and unmarried) according to marital status, and then the clinical characteristics of each group were compared using the chi-square test. Propensity score matching (PSM) was used to reduce differences in baseline characteristics. The overall survival (OS) and cervical cancer-specific survival (CCSS) were assessed by the Kaplan-Meier method, univariate and multivariate Cox regression models, and stratified analysis. Moreover, univariate and multivariate competing risk regression models were performed to calculate hazard ratios (HR) of death risk. RESULTS: A total of 21,148 patients were included in this study, including 10,603 married patients and 10,545 unmarried patients. Married patients had better OS(P < 0.05) and CCSS (P < 0.05) compared to unmarried patients, and marital status was an independent prognostic factor for both OS (HR: 0.830, 95% CI: 0.798-0.862) and CCSS (HR: 0.892, 95% CI: 0.850-0.937). Moreover, after eliminating the competing risk, married patients (CCSD: HR:0.723, 95% CI: 0.683-0.765, P < 0.001) had a significantly decreased risk of death compared to unmarried patients. In stratified analysis, the married patients showed better OS and CCSS than the unmarried patients diagnosed in 1975-2000 and 2001-2017. CONCLUSIONS: Being married was associated with a favorable prognosis of cervical cancer, and marital status was an independent prognostic factor for cervical cancer.

Sensitive NIR Fluorescence Identification of Bacteria in Whole Blood with Bioorthogonal Nanoprobes for Early Sepsis Diagnosis.

Sepsis is one of the leading causes of death worldwide. The disease progression of sepsis is very fast, and there is a 7-9% increase in mortality every hour. Therefore, rapid and sensitive detection of pathogenic bacteria is crucial for the timely treatment of sepsis as well as the reduction of mortality. Herein, we present a sensitive near-infrared (NIR) fluorescence identification and a rapid magnetic capture based on bioorthogonal nanoprobes for the detection of multiple bacteria in whole blood. The nanoprobes with NIR fluorescence/magnetic properties were modified with dibenzocyclooctyne groups and used to capture and recognize the bacteria via bioorthogonal reaction. The magnetic nanoprobes showed superparamagnetic properties with a saturation magnetization as high as 63 emu/g. Through clicking with the azide groups inserted on the bacteria walls by metabolic engineering, the bioorthogonal magnetic nanoprobes allow fast and broad-spectrum capture of both Gram-positive and Gram-negative bacteria. The bioorthogonal NIR fluorescent nanoprobes with a maximum emission at 900 nm can effectively avoid background interference, further enabling sensitive identification of the bacteria in whole blood. The detection limit was as low as 4 CFU/mL in less than 2.5 h and the nanoprobes were successfully applied to the detection of bacteria in blood samples from the patients with sepsis, showing the potential application in early sepsis diagnosis and clinical studies.

Coherent Sub-Nanometer Interface between Crystalline and Amorphous Materials Boosts Electrochemical Synthesis of Hydrogen Peroxide.

There are enormous yet largely underexplored exotic phenomena and properties emerging from interfaces constructed by diverse types of components that may differ in composition, shape, or crystal structure. It remains poorly understood the unique properties a coherent interface between crystalline and amorphous materials may evoke, and there lacks a general strategy to fabricate such interfaces. It is demonstrated that by topotactic partial oxidation heterostructures composed of coherently registered crystalline and amorphous materials can be constructed. As a proof-of-concept study, heterostructures consisting of crystalline P3 N5 and amorphous P3 N5 Ox can be synthesized by creating amorphous P3 N5 Ox from crystalline P3 N5 without interrupting the covalent bonding across the coherent interface. The heterostructure is dictated by nanometer-sized short-range-ordered P3 N5 domains enclosed by amorphous P3 N5 Ox matrix, which entails simultaneously fast charge transfer across the interface and bicomponent synergistic effect in catalysis. Such a P3 N5 /P3 N5 Ox heterostructure attains an optimal adsorption energy for *OOH intermediates and exhibits superior electrocatalytic performance toward H2 O2 production by adopting a selectivity of 96.68% at 0.4 VRHE and a production rate of 321.5 mmol h-1 gcatalyst -1 at -0.3 VRHE . The current study provides new insights into the synthetic strategy, chemical structure, and catalytic property of a sub-nanometer coherent interface formed between crystalline and amorphous materials.

Identification and characterization of a special type of subnuclear structure: AGGF1-coated paraspeckles.

AGGF1 is an angiogenic factor with G-Patch and FHA domains 1 described by our group. Gain-of-function mutations in AGGF1 cause Klippel-Trenaunay syndrome, whereas somatic loss-of-function mutations cause cancer. Paraspeckles are small membraneless subnuclear structures with a diameter of 0.5-1 µm, and composed of lncRNA NEAT1 as the scaffold and three core RNA-binding proteins NONO, PSPC1, and PSF. Here, we show that AGGF1 is a key regulatory and structural component of paraspeckles that induces paraspeckle formation, forms an outside rim of paraspeckles, wraps around the NONO/PSF/PSPC1/NEAT1 core, and regulates the size and number of paraspeckles. AGGF1-paraspeckles are larger (>1 µm) than conventional paraspeckles. RNA-FISH in combination with immunostaining shows that AGGF1, NONO, and NEAT1_2 co-localize in 20.58% of NEAT1_2-positive paraspeckles. Mechanistically, AGGF1 interacts with NONO, PSF, and HNRNPK, and upregulates NEAT1_2, a longer, 23 kb NEAT1 transcript with a key role in regulation of paraspeckle size and number. RNA-immunoprecipitation shows that AGGF1 interacts with NEAT1, which may be another possible mechanism underlying the formation of AGGF1-paraspeckles. NEAT1_2 knockdown reduces the number and size of AGGF1-paraspeckles. Functionally, AGGF1 regulates alternative RNA splicing as it decreases the exon skipping/inclusion ratio in a CD44 model. AGGF1 is also localized in some nuclear foci without NEAT1 or NONO, suggesting that AGGF1 is an important liquid-liquid phase separation (LLPS) driver for other types of AGGF1-positive nuclear condensates (referred to as AGGF1-bodies). Our results identify a special type of AGGF1-coated paraspeckles and provide important insights into the formation, structure, and function of paraspeckles.

Relationship between sleep disorders and female infertility among US reproductive-aged women.

PURPOSE: Sleep disorders are a risk factor for a wide variety of dysfunctions of endocrine, metabolic, cardiovascular, and neurological diseases. However, the risk of sleep disorders to female infertility has not been thoroughly explored. Our study aimed to examine whether or not sleep disorders increase the risk of female infertility. METHODS: Cross-sectional data on sleep disorders and fertility history were obtained from the National Health and Nutrition Examination Survey 2013-2018. Women aged 20 to 40 years old were enrolled in our study. Weighted multivariable logistic regression models and stratified analysis by age, smokers, and patient health questionnaire-9 (PHQ-9) score were conducted to estimate the effect of sleep disorders on female infertility. RESULT: Among 1820 reproductive-age females, 248 individuals had infertility and 430 individuals had sleep disorders. Two weighted logistic regression models found that sleep disorders were an independent risk factor for infertility. After adjusting for the covariates (age, race/ethnicity, marital status, education level, poverty income ratio, body mass index (BMI), waist circumference, PHQ-9 score, smokers, drinkers, and sleeping hours), the risk of infertility was 2.14-fold higher in individuals with sleep disorders than in those without. The further stratified analysis demonstrated that the relationship between sleep disorders and infertility was maintained and that the risk was higher particularly in infertile women aged 40-44 years, with PHQ-9 score greater than 10, and smokers. CONCLUSION: A strong association was found between sleep disorders and female infertility, and the association remained after adjusting for other confounding factors.

Association between the serum vitamin D level and prevalence of obesity/abdominal obesity in women with infertility: a cross-sectional study of the National Health and Nutrition Examination Survey data.

AIMS: To explore the relationship between vitamin D and obesity and abdominal obesity in women with infertility. MATERIAL AND METHODS: We screened the data from National Health and Nutrition Examination Survey (NHANES) 2013-2016. A total of 201 infertile women between the ages of 20 and 40 years were included in our study. To estimate the independent association of vitamin D with obesity and abdominal obesity, we used weighted multivariate logistic regression models and cubic spline analyses. RESULTS: Among infertile women in the NHANES 2013-2016 database, serum vitamin D levels were significantly and negatively associated with body mass index (ß= -0.96, 95% CI: -1.40, -0.51, p < 0.001)and waist circumference (ß= -0.40, 95% CI: -0.59, -0.22, p < 0.001), respectively. After multivariable adjustment, lower vitamin D levels were found to be associated with a higher prevalence of obesity (OR: 8.290, 95% CI: 2.451-28.039, p for trend = 0.001) and abdominal obesity (OR: 4.820, 95%CI: 1.351-17.194, p for trend =0.037). Spline regression showed linearity of the associations between vitamin D and obesity/abdominal obesity (p for nonlinearity > 0.05). CONCLUSION: Our findings suggested that a decreased vitamin D might correspond to a higher prevalence of obesity in infertile women, which reminded us to pay more attention to the supplement of vitamin D in obese infertile women.

Neutrophil CD64 index as a superior indicator for diagnosing, monitoring bacterial infection, and evaluating antibiotic therapy: a case control study.

BACKGROUND: Neutrophil CD64 (nCD64) index has been widely studied as an indication of bacteria-infected diseases, but the exact usage of nCD64 index in monitoring infections remains debated. So this study aims to investigate the functionality of nCD64 index in tracking infections' progression and evaluating antibiotic therapy. METHODS: 160 participants (36 healthy controls, 34 culture-negative patients, 56 respiratory tract infected patients, and 34 bloodstream infected patients) were recruited and divided into groups. Data on nCD64 index, T lymphocyte subsets, and conventional indicators, including white blood cell count, neutrophil to lymphocyte ratio, procalcitonin, and C-reactive protein, were tested and compared. RESULTS: Bacteria-infected patients had significantly higher nCD64 indexes (p < 0.05), especially patients with both bloodstream and respiratory tract infections. The nCD64 index could identify infected patients from culture-negative patients or controls, which conventional indicators cannot achieve. We followed up with 24 infected patients and found that their nCD64 indexes were promptly down-regulated after effective antibiotic therapy (3.16 ± 3.01 vs. 1.20 ± 1.47, p < 0.001). CONCLUSION: The nCD64 index is a sensitive indicator for clinical diagnosis of bacterial infection, especially in monitoring infection and evaluating antibiotics' efficacy. Therefore, nCD64 has the potential to improve diagnostic accuracy and provide rapid feedback on monitoring disease progression in infected patients.

Transcriptomic analysis of gene expression in normal goat ovary and intersex goat gonad.

Intersexuality is a congenital reproductive disorder that usually occurs in hornless goats, hindering breeding of goats with hornless traits and the development of the goat industry. In this study, we aimed to identify differentially expressed genes in intersex and normal goat gonads by comparing gene transcription profiles of intersex and normal goat gonads. As intersex goats are genetically based on females, we chose female goats as controls. The goats in the control group and the experimental group were both over one-year old. We evaluated the anatomical characteristics of the reproductive organs of five intersex goats using histopathological methods. The gonads were found to be ovarian and testicular types. RNA-Seq technology was used to identify differentially expressed genes in gonads and normal goat ovary tissues. Transcription analysis results were verified by qPCR. The results showed that 2,748 DEGs were upregulated and 3,327 DEGs were downregulated in intersex ovaries unlike in controls, whereas 2006 DEGs were upregulated and 2032 DEGs were downregulated in the interstitial testes. Many of these genes play important roles in mammalian sex determination and sex differentiation, such as SOX9, WT1, GATA4, DMRT1, DHH, AMH, CYP19A1 and FST. We found that many DEGs are involved in biological developmental regulation by GO and KEGG enrichment analyses, and that most genes associated with the steroid synthesis pathway were downregulated. The DEGs identified in this study may be involved in the regulation of intersex goat sex determination and differentiation, and may increase our understanding of the molecular mechanisms of mammalian sex differentiation.

Identification of mini-chromosome maintenance 8 as a potential prognostic marker and its effects on proliferation and apoptosis in gastric cancer.

Mini-chromosome maintenance (MCM) proteins play important roles in initiating eukaryotic genome replication. The MCM family of proteins includes several members associated with the development and progression of certain cancers. We performed online data mining to assess the expression of MCMs in gastric cancer (GC) and the correlation between their expression and survival in patients with GC. Notably, MCM8 expression was undoubtedly up-regulated in GC, and higher expression correlated with shorter overall survival (OS) and progression-free survival (PFS) in patients with GC. However, the role of MCM8 in GC has not been previously explored. Our in vitro experiments revealed that MCM8 knockdown inhibited cell growth and metastasis. Moreover, MCM8 knockdown induced apoptosis. Mechanistically, the expression levels of Bax and cleaved caspase-3 were increased, whereas Bcl-2 expression decreased. Additionally, we demonstrated that MCM8 knockdown suppressed tumorigenesis in vivo. Overall, these results suggest that MCM8 plays a significant role in GC progression.

Crucial Impact of Hydrophilicity on the Self-Assembled 2D Colloidal Crystals Using Langmuir-Blodgett Method.

Large-scale close-packed two-dimensional (2D) colloidal crystal with high coverage is indispensable for various promising applications. The Langmuir-Blodgett (LB) method is a powerful technique to prepare 2D colloidal crystals. However, the self-assembly and movement of microspheres during the whole LB process are less analyzed. In this study, we clarify the crucial impact of hydrophilicity of the microspheres on their self-assembly in the LB process and on the properties of the prepared 2D colloidal crystals. The characteristic surface pressure-area isotherms of the microspheres have been analyzed and adjusted by only counting the quantity of the microspheres on the water surface, which leads to more accurate results. The critical surface pressures for hydrophilic and hydrophobic microspheres are about 61 and 46 mN/m, respectively. The decrease of the surface hydrophilicity of microspheres facilitates their self-assembly on the water surface, which further leads to higher coverage and less defects of the 2D colloidal crystals. A coverage of as high as 97% was obtained using hydrophobic microspheres. Entropy and intersphere capillary forces drive the self-assembly and transportation of the microspheres, respectively. Caused by the diffraction of visible light, opposite contrasts at local adjacent regions on the surface of the 2D colloidal crystals have been observed. The understanding of self-assembly of the microspheres during the LB process paves the way to fabricate the high-quality 2D colloidal crystals for various applications such as photonic papers and inks, stealth materials, biomimetic coatings, and related nanostructures.

Review of Huang-huai sheep, a new multiparous mutton sheep breed first identified in China.

Huang-huai sheep are a new multiparous mutton sheep breed that has been cultivated by domestic scientific research institutes, governments, and sheep farms in China. Huang-huai sheep were bred using Dorper sheep as a sire and Small-tailed Han sheep as a dam. The breeding of Huang-huai sheep started in 2003, and three stages have been carried out: crossbreeding innovation, fixation in a two-way-crossbred closed flock, and herd propagation. A pilot test of Huang-huai sheep was conducted on 6 sheep farms from 2017 to 2018, and hereditary properties and production performance were evaluated in 2019. Huang-huai sheep were identified on site by the National Livestock and Poultry Resources Committee of China in December 2019 and approved as a new multiparous mutton sheep breed in China. The genetic distance showed that Huang-huai sheep are most closely related to Dorper sheep, Luxi black-headed sheep, and Small-tailed Han sheep, but the genetic distances are subspecies (0.02-0.20) each other. The body weights of adult Huang-huai sheep are 98.1 ± 5.2 kg (♂) and 71.7 ± 3.5 kg (♀), and those of 6-month-old Huang-huai sheep are 58.50 ± 6.55 kg (♂) and 52.45 ± 5.67 kg (♀). The slaughter rates of 6-month-old sheep are 56.02 ± 1.25% (♂) and 53.19 ± 1.19% (♀). The estrus cycle of Huang-huai sheep is 19.32 ± 2.8 days, the first estrus cycle occurs at 168 ± 12 days, the annual lambing rate of ewes is 252.82% ± 10.69%, the survival rate of lambs is 95.79 ± 0.95%, and the number of weaned lambs per ewe per year is 2.38 ± 0.14. The growth performance, carcass quality, and reproductive performance of Huang-huai sheep have been improved, resulting in considerable economic and social benefits and broader market prospects. This breed represents a new multiparous mutton sheep breed adapted for industrial sheep farms in China.

Metformin is associated with reduced cell proliferation in human endometrial cancer by inbibiting PI3K/AKT/mTOR signaling.

Metformin recently gained traction as potential anti-endometrial cancer agent for its new applications. However, the underlying mechanisms of the anti-cancer effect of metformin in the endometrial cancer have not yet been fully elucidated. Sixty-five patients diagnosed as endometrial carcinoma were grouped into (n = 33) and non-treatment mixed (n = 32) for analysis. Thirty healthy donors were recruited as controls. We attempt to investigate the effect of metformin on Ki-67, PI3K, p-AKT, p-S6K1, and p-4EBP1 staining in human endometrial cancer by immunohistochemical staining. We found that increased Ki-67 expression in women with endometrial cancer, which were reversed by conventional anti-diabetic doses of metformin in present work. In parallel, the reduced PI3K, p-AKT, p-S6K1, and p-4EBP1 staining induced by metformin appeared to play an important role for the anti-proliferative effects of metformin in endometrial cancer patients. Metformin significantly decreased proliferation in human endometrial cancer may by inhibiting PI3K/AKT/mTOR signaling. Our present results add to the growing body of evidence supporting metformin as a potential anti-cancer agent in endometrial cancer.

The Relationship Between Serum Zinc Levels, Cardiac Markers and the Risk of Acute Myocardial Infarction by Zinc Quartiles.

BACKGROUND: Zinc is one of the most important microelements in the body and zinc homeostasis plays a critical role in maintaining cellular structure and function. Zinc dyshomeostasis can lead to many diseases, such as cardiovascular disease. Our aim was to investigate whether there is a relationship between zinc and cardiac markers, and the risk of acute myocardial infarction (AMI) by zinc quartiles. METHODS: We enrolled a total of 529 patients and measured their serum zinc levels and cardiac markers. We performed further studies after dividing subjects into four groups according to their concentrations of zinc by quartile to clarify the relationship between zinc levels and risk of increased acute myocardial infarction prevalence rate. RESULTS: We observed that there was a significant inverse linear relationship between zinc and Lg(creatine kinase) (p=0.011), Lg(creatine kinase-MB) (p=0.002) and Lg(cardiac troponin T) (p=0.045). In addition, the acute myocardial infarction prevalence rates were 28.8%, 24.8%, 20.5%, and 18.2% by patients with zinc quartiles, respectively. Multivariate logistic regression analysis showed that the odds ratio between the lowest and highest zinc quartile groups was 1.92 (1.019-3.604) (p<0.05). CONCLUSIONS: The present study revealed a relationship between serum zinc levels in that zinc levels were significantly inversely correlated with serum creatine kinase (CK), creatine kinase-MB (CKMB) and cardiac troponin T (cTnT) levels. Furthermore, we found that the prevalence rate of acute myocardial infarction decreased with increasing zinc quartiles.

HfO2 high-k solid-state incandescent devices: performance improvement using a Ti-embedded layer and observation of conductive paths as light-emitting sources.

Solid-state incandescent light-emission devices (SSI-LEDs) with a metal-oxide-semiconductor structure are promising candidates for future broadband light-emission devices. In this work, the electrical and light-emission features of SSI-LEDs based on HfO2 high-k thin films with or without the Ti-embedded layer on p-type silicon wafers have been studied. It turns out that the Ti-embedded layer can effectively reduce the turn-on voltage, thus improving the fluorescence efficiency of SSI-LEDs. The combination of scanning electron microscopy, atomic force microscope (AFM) and conductive AFM results unambiguously clarifies that conductive filaments, which are formed due to local thermal excitation during the forming process, are accompanied by the formation of pits on the HfO2 surface and are responsible for the light emission. This work develops an effective approach to improving the luminescence performance of SSI-LEDs and experimentally explains the light-emitting mechanism of such devices, which is of great importance to eventually realizng broadband light-emitting devices with low power consumption.

Oxidative damage of the male reproductive system induced by paraquat.

The effects of paraquat (PQ) on the male reproductive system are unclear. In this study, male rats were divided into four groups (0, 0.5, 2, and 8 mg/kg) and treated with PQ by oral gavage for 8 weeks. At the end of the experiment, a significant decline in sperm count, motility, and viability and an increase in teratospermia were observed in the PQ-treated group (P < 0.05). Further investigation found that PQ resulted in enhanced lipid peroxidation and more apoptosis in the testis tissues, and apoptosis was likely to be associated with activation of the mitochondrial pathway. In summary, our study demonstrated oxidative damage due to PQ on the male reproductive system.

Dominant factors affecting reproductive outcomes of fertility-desiring young women with intrauterine adhesions.

PURPOSE: To identify the dominant factors affecting reproductive outcomes of fertility-desiring young women with intrauterine adhesions (IUA) after hysteroscopic adhesiolysis. METHODS: This prospective observational study included 104 cases of women with IUA. Logistic regression analysis was applied to analyze the value of the location and extent of adhesions, the number of previous uterine cavity surgery, menstrual patterns, and second look hysteroscopy time. RESULTS: In the total 104 patients with IUA, 91 patients (87.5%) had a history of at least one previous uterine cavity surgery. Hypomenorrhoea and amenorrhoea were two most common presenting menstrual abnormalities occurring in 59 (56.7%) and 28 (26.9%) cases, respectively. The clinical pregnancy rate was 60.6% (63/104) and the live birth rate was 39.4% (41/104). Pregnancy rate was higher in patients having mild IUA (81.5%) as compared to moderate (61.3%) or severe type (20.0%) (p < 0.001). The bivariate and binary logistic regression analysis revealed that the location and extent of adhesions were the independent parameters related to the reproductive outcome after hysteroscopic adhesiolysis for fertility-desiring women with IUA (p = 0.011 and p = 0.003, respectively), but not the number of previous uterine cavity surgery, menstrual patterns, and second look hysteroscopy time (p = 0.232, p = 0.239 and p = 0.120, respectively). CONCLUSION: The extent and location of IUA are the dominant factors affecting reproductive outcomes, which are possibly regarded as a potential predictor evaluating prognosis of IUA after hysteroscopic adhesiolysis.

[Effect of bear bile powder on STAT3 pathway in hepatocellular carcinoma xenograft].

OBJECTIVE: To observe the effect of bear bile powder (BBP) on the STAT3 pathway and its downstream target genes of nude mice hepatocellular carcinoma (HCC) xenograft, and to explore its mechanism for treating HCC. METHODS: The subcutaneous xenograft model was established using HepG2 cells. When the subcutaneous transplanted tumor was formed, naked mice were randomly divided into two groups, the BBP group and the control group. Mice in the BBP group were administered with BBP by gastrogavage, once daily for 3 consecutive weeks, while mice in the control group were administered with normal saline by gastrogavage, once daily for 3 consecutive weeks. The body weight and the tumor volume were measured once per week. By the end of medication, the tumor weight was weighed and the tumor inhibition ratio calculated. The apoptosis of the tumor tissue was detected by TdT-mediated dUTP nick end labeling (TUNEL). The expression of Bcl2-associated X protein (Bax), B cell lymphoma/eukemina-2 (Bcl-2), cyclin-dependent protein kinase (CDK4), cyclinD1 were detected by reverse transcription-polymerase chain reaction (RT-PCR). The protein expression levels of signal transducers and transcription activators 3 (p-STAT3), proliferating cell nuclear antigen (PCNA), Bax, Bcl-2, CDK4, and cyclinD1 were determined by immunohistochemistry. RESULTS: BBP could inhibit the tumor volume and tumor weight, showing statistical difference when compared with the control group (P < 0.01). Results of TUNEL showed that BBP could significantly induce the apoptosis of hepatoma carcinoma cells. Results of RT-PCR showed that BBP could up-regulate the expression of Bax and down-regulate mRNA expression of Bcl-2, CDK4, and cyclinD1. Immunohistochemical results showed that BBP could up-regulate the expression of Bax and inhibit the protein expression of p-STAT3, PCNA, Bcl-2, CDK4, and cyclinD1. CONCLUSION: BBP could induce the apoptosis of hepatoma carcinoma cells and inhibit their proliferation by regulating STAT3 pathway.

Effects of MTHFR C677T polymorphism on homocysteine and vitamin D in women with polycystic ovary syndrome.

OBJECTIVES: To evaluate the correlation between serum vitamin D, homocysteine and the methylene tetrahydrofolate reductase (MTHFR) C677T polymorphism in women with polycystic ovary syndrome (PCOS). Study design We retrospectively compared the serum homocysteine and vitamin D levels and the MTHFR C677T polymorphism in 104 PCOS patients and 104 controls. Parameters related to PCOS were statistically analysed. RESULTS: Comparative analysis revealed that women with PCOS had significantly greater serum homocysteine levels (P = 0.002) and lower vitamin D concentrations (P = 0.040) than controls. The distribution frequency of the MTHFR C677T genotype did not significantly differ between the PCOS group and the control group. (P > 0.05). In the PCOS group, the serum level of homocysteine in the TT group was significantly greater than that in the CT (P = 0.003) and CC (P = 0.002) groups and the level of vitamin D in the TT group was significantly less than that in the CC (P < 0.001) and CT (P = 0.172) groups. The results were similar when the PCOS and control groups were divided according to whether they had insulin resistance. Vitamin D levels were significantly negatively correlated with homocysteine levels in all PCOS patients (r = -0.281, P = 0.004), similarly, vitamin D levels were negatively correlated with homocysteine levels in the CC, CT and TT of PCOS patients. According to multivariate analysis, vitamin D concentration was an independent risk factor for hyperhomocysteinaemia (adjusted OR 1.372, 95 % CI: 1.100-1.712). CONCLUSIONS: No significant differences were found in the distributions of MTHFR C677T genotypes between the PCOS and control groups but these genotypes affected the patients' serum homocysteine and vitamin D concentrations. Women with the TT genotype have significantly lower vitamin D levels and higher homocysteine levels than women with the CC and CT genotypes. However, because of the limitations of this investigation, large-sample, high-quality prospective studies are needed to further verify these results in the future.

Serum 25-hydroxyvitamin D is associated with homocysteine in infertile patients with polycystic ovary syndrome (PCOS).

OBJECTIVES: The aim of the study was to investigate whether there is a relationship between serum 25-hydroxyvitamin D and homocysteine in infertile-related PCOS. MATERIAL AND METHODS: We retrospectively reviewed 208 participants (86 PCOS and 122 non-PCOS) who met the inclusion and exclusion criteria from March 2020 to October 2021 at the Department of Obstetrics and Gynecology of the Second affiliated hospital of Xi'an Jiaotong University. Methods of Pearson correlation and linear regression were used to evaluate the associations between serum levels of 25-hydroxyvitamin D and homocysteine in infertile-related PCOS, and a smooth curve fitting were used to address potential nonlinearity. RESULTS: An inverse association between serum 25-hydroxyvitamin D and homocysteine was observed (r = -0.392, p < 0.001) in PCOS groups. Multiple linear regression analysis showed serum 25-hydroxyvitamin D was independently negatively associated with homocysteine levels after controlling for confounding factors (ß = -0.316, p = 0.006). Age, BMI-stratified multivariate linear regression showed that serum 25-hydroxyvitamin D were independently associated with hyperhomocysteine especially in PCOS women aged 30 years or younger after adjusting age, BMI, and AMH. CONCLUSIONS: Herein, the current findings suggest that 25-hydroxyvitamin D levels was negatively associated with serum homocysteine in women with infertility-related PCOS.