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The protein C (PC) system has proven to be a crucial cascade in systemic inflammatory and coagulopathic disorders such as severe sepsis and, more recently, in severe burns. We aimed to conflate our recent systemic findings with further investigations in the local tissue effects of a severe burn injury on the expression of PC and its main receptor endothelial protein C receptor (EPCR). Of the 86 patients enrolled in our recent study, 34 consented to biopsies of both normal and burn edge tissue. These were examined histologically and immunostained for PC, EPCR, and CD68. The burn samples expressed lower PC (p = 0.0027) and higher EPCR (p = 0.0253) than the normal samples in a histological severity-dependent manner. There was also a negative association between PC expression and CD68 positive macrophage infiltration (τb = −0.214, p = 0.020), which was expectedly higher in burn edge samples (p &lt, 0.0005). Interestingly, while there were no correlations between tissue and plasma PC or EPCR, local PC expression was also prognostic of our previously established outcome of a patient requiring increased medical support (OR 0.217 (95%CI 0.052 to 0.901), p = 0.035). The results suggest that local PC cascade changes from a burn injury may be a separate process to the systemic effects and that the local levels may provide useful information in addition to the diagnostic and prognostic abilities we previously found in the circulating PC system.

MicroRNAs (miRNAs) are of importance to chronic heart failure (CHF). However, the relevance of the exosomal miRNAs produced during CHF remains unknown. Our purpose here was to examine the relevance of exosomal miR-1246 released from human umbilical cord mesenchymal stem cell (hucMSC) during CHF and the mechanism of action. Cardiac function, myocardial infarction area, apoptosis, and angiogenesis were all evaluated in a CHF rat model following treatment with hucMSC-derived exosomes (hucMSC-Exos). H9C2 and human umbilical vascular endothelial cells (HUVECs) were subjected to oxygen and glucose deprivation and exosome treatment to quantify the cell proliferation and apoptosis in H9C2 cells and the tube formation capacity of the HUVECs. A dual-luciferase activity reporter assay was conducted to validate the interaction between miR-1246 and serine protease 23 (PRSS23). HucMSCs treatment led to a reduction in H9C2 apoptosis and an increase in HUVEC angiogenesis, which were mitigated when hucMSCs were treated with an miR-1246 inhibitor. We also confirmed that PRSS23 is a putative target of miR-1246 and that miR-1246 attenuated hypoxia-induced myocardial tissue damage by targeting PRSS23 and inhibiting the activation of the Snail/α-SMA signaling. Our findings suggest that exosomal miR-1246 from hucMSCs protects the heart from failure by targeting PRSS23. This article is protected by copyright. All rights reserved.

Jing Liu,1– 3 Liying Guan,4 Meng Zhao,1,2,5 Qihang Li,2,3,5 An Song,6 Ling Gao,2,7,8 Haiyan Lin,4 Jiajun Zhao1,2,5,7 1Department of Endocrinology, Shandong Provincial Hospital, Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of China; 2Shandong Clinical Medical Center of Endocrinology and Metabolism, Affiliated to Shandong Provincial Hospital, Jinan, Shandong, 250021, People’s Republic of China; 3Shandong Institute of Endocrine and Metabolic Disease, Affiliated to Shandong Provincial Hospital, Jinan, Shandong, 250021, People’s Republic of China; 4Health Management Center, Shandong Provincial Hospital, Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 5Department of Endocrinology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250021, People’s Republic of China; 6Peking Union Medical College Hospital, Affiliated to Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China; 7Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Affiliated to Shandong Provincial Hospital, Jinan, Shandong, 250021, People’s Republic of China; 8Department of Scientific Center, Shandong Provincial Hospital, Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of ChinaCorrespondence: Haiyan LinHealth Management Center, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jing 5 Road, Jinan, Shandong, 250021, People’s Republic of ChinaTel +86-531-68776123 (Clin.)Fax +86-531-87068707Email zxhlhy@126.comJiajun ZhaoDepartment of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jing 5 Road, Jinan, Shandong, 250021, People’s Republic of ChinaTel +86-531-68776375 (Clin.); +86-531-68776094 (Lab.)Fax +86-531-87068707Email jjzhao@sdu.edu.cnBackground: Nonalcoholic fatty liver disease (NAFLD) is increasingly becoming a major health burden. Due to the difficulty of liver biopsy, there is no reliable indicator to evaluate the outcomes of NAFLD. The triglyceride–glucose (TyG) index is a simple and convenient marker of insulin resistance for use in medical practice. Whether the TyG index is predictive of later risk of NAFLD remains unknown.Objective: To evaluate the relationship between TyG index with NAFLD progression and improvement during a median follow-up period of 21 months.Material and Methods: A total of 11,424 subjects (9327 men) diagnosed with NAFLD were included. The TyG index was calculated as follows: ln [fasting triglycerides (mg/dL) * fasting glucose (mg/dL)/2]. Multivariable Cox regression analysis was applied to analyze the data.Results: In this study, the severity of NAFLD remained the same in 38.8% of subjects, worsened in 17.4% of subjects, and improved in 43.8% of subjects. Compared with the lowest quartile of the TyG index, the adjusted HR of NAFLD progression in the highest quartile (TyG≥ 9.34) was 1.448 (1.229 to 1.706), and the adjusted HR of NAFLD improvement was 0.817 (0.723 to 0.923). Subgroup analysis found that smoking increased the correlation between the TyG index and the risk of NAFLD progression, while female, vegan diet, and weight control enhanced the correlation between the TyG index and the risk of NAFLD improvement.Conclusion: The TyG index may be a simple and helpful indicator for further risk appraisal of NAFLD in daily clinical practice.Keywords: triglyceride–glucose index, nonalcoholic fatty liver disease, outcomes

This study was carried out to explore the promotion role of computed tomography (CT) imaging three-dimensional (3D) reconstruction technology and rapid rehabilitation nursing intervention (RRNI) in the treatment of patients with renal cell cancer (RCC) laparoscopic radical nephrectomy (LRN) in view of the patient’s condition. 98 RCC patients who were admitted to the hospital from July 2019 to July 2020 were selected as the research subjects, and all patients underwent the LRN and the RRIN. Of which, 46 RCC patients were scanned with CT images (regarded as the CT group), and 46 RCC patients were scanned with CT images based on 3D reconstruction algorithms (regarded as the 3D CT group). The clinical efficacy and the life quality, pain degree, and adverse mood changes before and after the RRN were analyzed and compared. The results showed that the surgery time in the 3D CT group and the CT group was 130.2 ± 42.8 minutes and 162.4 ± 38.5 minutes, respectively ( P < 0.05 ). The recurrence rate of RCC in both groups was 0%. The estimated blood loss in the 3D CT group and the CT group was 93.6 ± 35.5 mL and 90.3 ± 40.2 mL, respectively; the complication rate in the 3D CT and CT group was 5% and 12%, respectively; the hospital stay in the 3D CT and CT group was 12.5 ± 4.7 days and 12.1 ± 3.2 days, respectively, which had no statistical significance ( P > 0.05 ). The scores of visual analogue scale (VAS), 36-Item Short-Form Health Survey (SF-36), self-rating depression scale (SDS), and self-rating anxiety scale (SAS) of patients in the two groups were statistically significant ( P < 0.05 ). It indicated that CT images based on the 3D reconstruction algorithm could be applied in LRN of RCC patients to shorten the surgery time and improve the surgical effect, and implementation of the RRN could relieve the adverse mood of RCC patients and effectively improve their life quality.

Chronic active Epstein-Barr virus (CAEBV) infection is a rare disease with a high mortality rate. Our study aimed to summarize the clinicopathological characteristics of CAEBV infection in adults and improve knowledge of the disease. Data for 19 adult patients with CAEBV confirmed at our hospital from January 2010 to December 2019 were collected retrospectively. There were 14 males and 5 females, and the median age was 33 years (range 14-83). The main clinical manifestations included recurrent fever (84.2%, 16/19), splenomegaly (89.5%, 17/19), hepatomegaly (73.6%, 14/19), lymphadenopathy (42.1%, 8/19), abnormal liver function (78.9%, 15/19), hemopenia (94.7%, 18/19), and hemophagocytosis (52.6%, 10/19). A total of 22 specimens were collected from 19 patients for histopathology. Most of the biopsy specimens showed lymphocyte infiltration. Immunohistochemical staining and EBV-encoded small RNA (EBER) in situ hybridization were performed for 14 of the 22 samples. CD3 and CD20 staining were positive, with more CD3-positive cells than CD20-positive cells (100%, 14/14), and EBER in situ hybridization was positive in most cases (85.7%, 12/14). More than half of TCR gene rearrangement tests showed monoclonal rearrangement (66.6%, 4/6). Mortality was high, with most CAEBV patients dying during the period from diagnosis to the end of follow-up (12/19, 63%); the median survival time was only 20.75 months. Based on limited data, we consider that CAEBV is a disease with different ages of onset and is a complex and heterogeneous syndrome with features of both immunodeficiency and malignant neoplasms. Furthermore, the prognosis of adult-onset CAEBV appears to be very poor.

In order to understand the psychological problems of pregnant women, this article explores the psychological problems and the sources of psychological stress of pregnant women who have a history of recurrent miscarriage after pregnancy. The analysis shows that the psychological stress of pregnant women may be one of the reasons for recurrent miscarriage. Strengthening mental health education during pregnancy can avoid the stimulation of bad emotions and environment, prevent the spontaneous abortion caused by psychological reasons, and improve the quality of pregnancy. It is particularly important to grasp the mental state of pregnant women with recurrent abortion timely and carry out corresponding psychological counseling and psychological nursing.

Rapamycin has been proven to effectively inhibit the activation of primordial follicles while cisplatin-induced the loss of primordial follicles due to the over-activation of the primordial follicle stockpile. Whether rapamycin could inhibit the loss of primordial follicles induced by cisplatin is still unknown. The ovaries of neonatal Sprague Dawley rats were cultured in vitro in different doses of rapamycin (0.08, 0.16, and 0.32 μg/ml) and cisplatin (0.1, 0.4, and 0.8 μg/ml). The immature BALB/c mice were administered cisplatin with or without rapamycin by intraperitoneal injection. Ovaries were collected to analyze the histomorphology, the messenger RNA (mRNA) expression of anti-Mullerian hormone (AMH), growth differentiation factor 9 (GDF9), and bone morphogenetic protein 15 (BMP15) and the expression of key proteins of mammalian target of rapamycin (mTOR) pathway. Growing follicle counts of ovaries cultured in vitro in the R0.16 and R0.32 groups were decreased and the ratio of growing to primordial follicles was also decreased in a dose-dependent manner. In the C0.8 group, growing follicles were decreased compared with the other groups while the ratio was substantially increased in the C0.4 and C0.8 group. Co-treatment attenuated primordial follicle loss and reduced the upregulated ratio induced by cisplatin. Ovarian follicle dynamics in vivo was consistent with the in vitro results. Primordial follicles counts were statistically increased and the ratio was reduced in the rapamycin group compared with the control group. Primordial follicle counts were dramatically reduced in the cisplatin group whereas co-treatment with rapamycin slightly recovered its counts. There was no obvious difference in the number of growing follicles between the cisplatin group and other groups. The ratio was significantly increased in cisplatin-treated mice whereas decreased in the co-treatment group. The apoptosis rate of antral follicles in cisplatin-treated mice was higher than the other groups while the apoptosis rate was decreased in the co-treatment group in vivo. Compared with the control and rapamycin group, the mRNA expression of AMH, GDF9, and BMP15 were downregulated in the cisplatin group. The co-treatment group recovered the mRNA expression of BMP15. In addition, the expression of key protein of mTOR pathway rpS6 and its phosphorylated forms were increased in the cisplatin-treated group while co-treatment decreased their expression. Rapamycin attenuated the loss of primordial follicles induced by cisplatin through the inhibitory effect of rapamycin on the mTOR pathway. These results suggest that rapamycin may be an effective drug for the protection of ovarian function during chemotherapy.

Objective:. Subjective tinnitus is characterized by the perception of sound in the absence of any external auditory stimuli. This perceived sound may be related to altered intrinsic neural activity generated along the central auditory pathway. This retrospective study was designed to investigate regional homogeneity and functional connectivity in the resting-state brain activity of patients with tinnitus. Methods:. We recruited tinnitus patients with normal hearing or mild hearing loss (n = 17) and age-matched healthy controls (n = 20), and examined regional homogeneity and functional connectivity in resting-state brain activity using resting-state functional magnetic resonance imaging data. The present study protocol was approved by the Institutional Review Board on Experimental Ethics at Sun Yat-sen University, China (approval No. SYSEC-KY-KS-2019-083). Results:. Compared with normal controls, patients with tinnitus had significantly decreased regional homogeneity in the anterior lobe of the cerebellum and increased homogeneity in the inferior frontal gyrus (P

Data from in vitro and animal studies support the preventive effect of tea (Camellia sinensis) against colorectal cancer. Further, many epidemiologic studies evaluated the association between tea consumption and colorectal cancer risk, but the results were inconsistent. We conducted a meta-analysis of prospective cohort studies to systematically assess the association between tea consumption and colorectal cancer risk. A comprehensive literature review was conducted to identify the related articles by searching PubMed and Embase up to June, 2019. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated using a fixed effect model. Twenty cohort articles were included in the present meta-analysis involving 2,068,137 participants and 21,437 cases. The combined RR of colorectal cancer for the highest vs. lowest tea consumption was determined to 0.97 (95% CI 0.94–1.01) with marginal heterogeneity (I2 = 24.0%, P = 0.093) among all studies. This indicated that tea consumption had no significant association with colorectal cancer risk. Stratified analysis showed that no significant differences were found in all subgroups. We further conducted the gender-specific meta-analysis for deriving a more precise estimation. No significant association was observed between tea consumption and colorectal cancer risk in male (combined RR = 0.97; 95% CI 0.90–1.04). However, tea consumption had a marginal significant inverse impact on colorectal cancer risk in female (combined RR = 0.93; 95% CI 0.86–1.00). Further, we found a stronger inverse association between tea consumption and risk of colorectal cancer among the female studies with no adjustment of coffee intake (RR: 0.90; 95% CI 0.82–1.00, P 0.05). Our finding indicates that tea consumption has no significant impact on the colorectal cancer risk in both genders combined, but gender-specific meta-analysis shows that tea consumption has a marginal significant inverse impact on colorectal cancer risk in female.

PurposeTo determine the impact of ovarian endometrioma per se on in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes.MethodsThis retrospective study was conducted using two groups. The endometrioma group consisted of 862 women with infertility who had ovarian endometriomas and underwent their first ovarian stimulation for IVF/ICSI treatment between January 2011 to December 2019 at a public university hospital. A non-endometrioma comparison group, comprising 862 women with other infertility factors, was matched according to maternal age, body mass index (BMI), and infertility duration. Ovarian reserve and response and IVF/ICSI and pregnancy outcomes between the two groups were analyzed. Multivariate logistic regression (MLR) analysis was conducted on the basis of clinical covariates assessed for their association with live birth.ResultsThe results showed that significantly lower antral follicle count (AFC), anti-Müllerian hormone (AMH), ovarian sensitivity index (OSI), oocyte maturation and fertilization rates, blastocyst rate, number of oocytes retrieved, and available embryos were found in women with endometrioma compared with the control, respectively (P < 0.05). The cumulative live birth rate per patient in women with endometrioma was lower than that of women without endometrioma (39.32% vs. 46.87%, P = 0.002). In women with endometrioma, those who underwent surgical intervention prior to IVF/ICSI treatment had higher maturation (86.03% vs. 83.42%, P = 0.003), fertilization (78.16% vs. 74.93%, P = 0.004), and top-quality embryo rates (42.94% vs. 39.93%, P = 0.097) but had fewer oocytes retrieved (8.01 ± 5.70 vs. 9.12 ± 6.69, P = 0.013) than women without surgery. However, live birth rates were comparable between women with endometrioma and women in the control group, regardless of whether they had a prior history of ovarian surgery. MLR analysis showed no correlation between endometrioma per se and live birth after being adjusted for number of top-quality embryos transferred and stage of embryo transfer.ConclusionsThe data from this study supported the conclusion that ovarian endometrioma negatively impacts oocyte quality and quantity, but not overall pregnancy outcomes, in women undergoing IVF/ICSI treatment. Endometrioma lowers the cumulative live birth rate by decreasing the number of embryos. Surgical excision of endometrioma prior to IVF/ICSI can partly improve oocyte maturation and fertilization rates but not pregnancy outcomes.

Background: Chronic active Epstein-Barr virus hepatitis (CAEBVH) in adult patients is a rare and highly lethal disease characterized by hepatitis and hepatomegaly.Aims: To investigate the clinicopathological features and pathogenic mechanisms in patients with CAEBVH.Methods:10 adult patients confirmed CAEBVH infection were collected. The clinicopathological characteristics were summarized and analyzed by clinical data. Flow cytometry to detect peripheral blood immune cell phenotypes, second-generation sequencing methods to explore pathogenic mechanisms, and immunohistochemical methods to verify pathogenic mechanisms.Results: The clinical features included splenomegaly, hepatomegaly, abnormal liver function, and CD8+T lymphopenia. HE also showed lymphocytic infiltration in liver tissue. EBER-ISH in lymphocytes of liver tissues were positive. Whole exon sequencing showed mutant genes were primarily enriched in 'T cell activation' and 'Complement and coagulation cascades'. The expression of CD8 in the CAEBVH group was higher than the controls in liver tissue (ppp

Background There is few predictive tools for live birth in women with adenomyosis, which provide further personalized and clinically specific information related to individualized decisions making during IVF/ICSI treatment. Methods A total of 424 patients with adenomyosis underwent frozen-thawed embryo transfer (FET) from Jan 2013 to Dec 2019 at a public university hospital were included. The patients were randomly divided into training (n = 265) and validation (n = 159) samples for the building and testing of the nomogram, respectively. Multivariate logistic regression (MLR) was developed on the basis of clinical covariates assessed for their association with live birth. Results In all, 183 (43.16%) patients became pregnant, and 114 (26.88%) had a live birth. In the multivariable analysis of the training cohort, probability of live birth was significantly correlated with the age 3 (OR, 8.141; 95% CI, 2.170–10.542; P = 0.002), blastocyst transfer (OR, 3.231; 95% CI, 1.065–8.819, P = 0.023), twin pregnancy (OR, 0.328; 95% CI, 0.104–0.344, P = 0.005) and protocol in FET (P

Background Circadian rhythm is an important player for reproduction. Rev-erbα, a significant clock gene, is involved in regulating cell differentiation, inflammation and metabolism. Macrophage polarization plays crucial roles in immune tolerance at the maternal-fetus interface, which also modulates the initiation and resolution of inflammation. Alteration of macrophage polarization induces adverse pregnancy outcomes such as infertility, recurrent spontaneous abortion and preterm labor. Results Decidual macrophages from LPS-induced mice abortion model displayed M1-like bias, accompanied by decreased expression of Rev-erbα. SR9009, an agonist of Rev-erbα, may reduce lipopolysaccharide (LPS)-induced M1 polarization of macrophages via activation of PI3K but not NF-κB signaling pathway. Furthermore, SR9009 could reduce M1-like polarization of decidual macrophages induced by LPS and attenuate LPS-induced resorption rates in mice model. Conclusions Both in vivo and in vitro experiments demonstrated that the pharmacological activation of Rev-erbα using SR9009 could attenuate the effect of LPS on macrophage polarization and protect pregnancy. This study may provide a potential therapeutic strategy for miscarriage induced by inflammation.

ObjectiveMenopause contributes to renal dysfunction in women, which is generally attributed to estrogen withdrawal. In addition to decreased estrogen level, serum follicle-stimulating hormone (FSH) level increases after menopause. This study investigated the association between high circulating FSH level and renal function in post-menopausal women.MethodsThis observational cross-sectional study included 624 pre-menopausal, 121 peri-menopausal, and 2540 post-menopausal women. The levels of female sex hormones were examined by chemiluminescence and indices of renal function were measured using a clinical chemistry analyzer. The post-menopausal women were grouped into quartiles according to serum FSH levels.ResultsRenal function progressively declined from pre-menopause to peri-menopause to post-menopause, which was accompanied by increasing serum FSH level. In post-menopausal women, serum creatinine level increased with increasing FSH quartile, which was accompanied by a decrease in estimated glomerular filtration rate (eGFR) (p for trend 2) and chronic kidney disease (CKD; eGFR 2) increased (p for trend ConclusionsA high circulating FSH level is an independent risk factor for renal dysfunction in women after menopause. Additionally, aging may aggravate the association of high FSH levels with reduced renal function in post-menopausal women.

Centromere proteins (CENPs) are the main constituent proteins of kinetochore, which are essential for cell division. In recent years, several studies have revealed that several CENPs were aberrantly expressed in hepatocellular carcinoma (HCC). However, numerous centromere proteins have not been studied in HCC. In this study, we used databases of Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), the Kaplan-Meier Plotter, cBioPortal, the Human Protein Atlas (HPA), and TIMER (Tumor Immune Estimation Resource) and immunohistochemical staining of clinical specimens to investigate the expression of 15 major centromere proteins in HCC to evaluate their potential prognostic value. We found that the mRNA levels of 4 out of 15 centromere proteins (CENPL, CENPQ, CENPR, and CENPU) were significantly higher in HCC than in normal tissues, and their mRNA levels were associated with the tumor stages ( p values < 0.01). Patients with higher mRNA levels of CENPL had poorer overall survival, progression-free survival, relapse-free survival, and disease-specific survival ( p values < 0.05). Furthermore, the higher levels of CENPL mRNA were associated with worse overall survival in males without hepatitis virus infection ( p values < 0.05). The protein expression level of CENPL in human HCC tissue was higher than that in normal liver tissue. In addition, the expression of CENPL was positively correlated with the levels of the tumor-infiltrating lymphocytes. The results suggest that the high mRNA expression of CENPL may be a potential predictor of prognosis in HCC patients.

Do frozen embryo transfer (FET) cycles following long-term gonadotrophin-releasing hormone agonist (GnRHa) pretreatment have better pregnancy outcomes than fresh embryo transfer cycles with long or ultra-long GnRHa protocol in these patients?This study included 537 women with adenomyosis divided into three groups: (Group A) FET cycles following long-term GnRHa pretreatment (192 patients); (Group B) fresh embryo transfer cycles with the ultra-long GnRHa protocol (241 patients); (Group C) fresh embryo transfer cycles with the long GnRHa protocol (104 patients).The total gonadotrophin dose and stimulation duration were significantly lower in Group A than in Groups B and C. The implantation and live birth rates were significantly higher in Group A than in Groups B and C. In the long-term GnRHa pretreatment and FET treatment of Group A, implantation (odds ratio [OR] 1.729, 95% confidence interval [CI] 1.073-2.788, P = 0.025), clinical pregnancy (OR 1.665, 95% CI 1.032-2.686, P = 0.037) and live birth rates (OR 1.694, 95% CI 1.045-2.746, P = 0.033) increased and miscarriage rate (OR 0.203, 95% CI 0.078-0.530, P = 0.001) decreased when compared with Group C. Comparison of Groups A and B showed that with the long-term GnRHa pretreatment, FET was a protective factor for live birth rate (OR 1.350, 95% CI 1.017-1.792, P = 0.038).FET following long-term GnRHa pretreatment has a better IVF/intracytoplasmic sperm injection outcome, and a potential benefit in terms of a lower gonadotrophin dose, and a shorter stimulation duration than fresh embryo transfer combined with a long or ultra-long GnRHa protocol.

Background Nanodiamonds (NDs) have been demonstrated to have bactericidal activity on several microorganisms and can be used in various kinds of dental materials. NDs are potential candidates for antibacterial dental materials. However, the possible inhibitory effect of NDs on oral pathogenic bacteria is largely unknown. This study was performed to investigate the inhibitory effects of carboxylated nanodiamond (cND) on Streptococcus mutans. Methods Fourier transform infrared spectroscopy was used to confirm carboxyl groups on the surface of commercial cND. The inhibitory effect of serially diluted cND on S. mutans was evaluated by spectrophotometry and plating methods. Escherichia coli was treated as a positive control in spectrophotometry. Chlorhexidine was used as a positive control in plating methods. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were employed to confirm the antibacterial activity of cND. Results The results showed that cND exhibited a significant inhibitory effect on S. mutans. For S. mutans, the minimum inhibitory concentration was 4 μg/ml and the minimum bactericidal concentration was 16 μg/ml. SEM and TEM results indicated that cND functioned as an antibacterial agent, likely due to its ability to disrupt the cell membrane of S. mutans. Conclusion In conclusion, these findings demonstrated an inhibitory effect of cND on S. mutans and suggest its use as a potential antibacterial dental material., Nanodiamonds have been demonstrated to have bactericidal activity on several microorganisms and can be used in various kinds of dental materials. Nanodiamonds are potential candidates for antibacterial dental materials. However, the possible inhibitory effect of nanodiamonds on oral pathogenic bacteria is largely unknown. The present study was performed to investigate the inhibitory effects of carboxylated nanodiamond (cND) on Streptococcus mutans (S. mutans). Fourier transform infrared spectroscopy was used to confirm carboxyl groups on the surface of commercial cND. The inhibitory effect of serially diluted cND on S. mutans was evaluated by spectrophotometry and plating methods. Escherichia coli was treated as a positive control in spectrophotometry. Chlorhexidine was used as a positive agent control in plating methods. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were employed to confirm the antibacterial activity of cND. The results showed that cND exhibited a significant inhibitory effect on S. mutans. For S. mutans, the minimal inhibitory concentration (MIC) was 4 μg/ml, and the minimum bactericidal concentration (MBC) was 16 μg/ml. SEM and TEM results indicated that cND functioned as an antibacterial agent, likely due to its ability to disrupt the cell membrane of S. mutans. In conclusion, these findings demonstrated an inhibitory effect of cND on S. mutans and suggest its use as a potential antibacterial dental material.

Problem Circadian rhythms are involved not only in the repair and regeneration of the immune system, but may also be associated with regulation of inflammation and immune responses. Rev-erbα could constitute a link between immunity and circadian rhythms since it is a transcription factor that regulates circadian rhythms and has functions in multiple physiological and pathological processes. Decidual macrophages (dMφs) play crucial roles in immune balance at the maternal-fetal interface, and abnormal macrophage polarization is related to adverse pregnancy outcomes, such as infertility, recurrent spontaneous abortion, and preterm labor. However, whether Rev-erbα could modulate the polarization of macrophages is unknown. Methods of study In this study, we analyzed the phenotype of dMφs and the expression of Rev-erbα in dMφs from normal pregnancies and miscarriages. The effect of Rev-erbα on macrophage polarization was evaluated by its knockdown or pharmacological activation. The mechanism by which the Rev-erbα agonist SR9009 regulates macrophage polarization was also estimated. Results A type-1 macrophage (M1)-like dominance was observed in dMφs from human miscarriages, with a decreased expression of Rev-erbα compared to that from normal pregnancies. Rev-erbα knockdown promoted M1 polarization in macrophages differentiated from the THP1 cell line, whereas pharmacological activation of Rev-erbα by SR9009 induced type-2 macrophage (M2)-like polarization in dMφs. Furthermore, we found that SR9009 induced M2 polarization in macrophages differentiated from the U937 cell line via the PI3K/Akt signaling pathway. Conclusion Rev-erbα may play an essential role in macrophage polarization. These findings might help elucidate the role of Rev-erbα in regulating the differentiation and functions of macrophages and suggest a therapeutic target for pregnancy loss and pregnancy complications.

ObjectiveThis study aimed to compare the ultra-long gonadotropin-releasing hormone agonist (GnRH-a) protocol and the long GnRH-a protocol during in vitro fertilization (IVF) or intracytoplasmic sperm (ICSI) treatment on fertility outcomes in women with adenomyosis.Materials and MethodsThis study was a retrospective cohort study. From January 2011 to May 2018, a total of 371 fresh IVF/ICSI cycles were included. Among the cycles included, 237 cycles of 212 women underwent the ultra-long GnRH-a protocol, while 134 cycles of 116 women underwent the long GnRH-a protocol. The rates of implantation, clinical pregnancy per embryo transfer, live birth, and early miscarriage were estimated between the compared protocols.ResultsIn the study, the early miscarriage rate in women undergoing the ultra-long GnRH-a protocol was significantly lower than those undergoing the long GnRH-a protocol (12.0% versus 26.5%, p = 0.045), whereas the differences in the rates of biochemical pregnancy, implantation, clinical pregnancy, and live birth in women between the two groups showed no statistical significance. The pregnancy outcomes were also sub-analyzed according to the adenomyotic region (diffuse and focal). As for diffuse adenomyosis, the rates of clinical pregnancy and live birth in women undergoing the ultra-long GnRH-a protocol were significantly higher than those undergoing the long GnRH-a protocol (55.3% versus 37.9%, p = 0.025; 43.4% versus 25.9%, p = 0.019, respectively). However, pregnancy outcomes showed no difference between the two protocols in women with focal adenomyosis.ConclusionsThe ultra-long GnRH-a protocol during IVF/ICSI improves pregnancy outcomes in women with adenomyosis, especially in women with diffuse adenomyosis when compared with the long GnRH-a protocol.

Corticosteroid-binding globulin (CBG) is a high-affinity plasma protein that binds glucocorticoids (GCs) and regulates their biological activities. The structural and functional properties of CBG are crucial to understanding the biological actions of GCs in mediating stress responses and the underlying mechanisms. In response to stress, avian CBGs modulate the free and bound fractions of plasma corticosterone (CORT, the main GC), enabling them to mediate the physiological and behavioral responses that are fundamental for balancing the trade-off of energetic investment in reproduction, immunity, growth, metabolism and survival, including adaptations to extreme high-elevation or high-latitude environments. Unlike other vertebrates, avian CBGs substitute for sex hormone-binding globulin (SHBG) in transporting androgens and regulating their bioavailability, since birds lack an Shbg gene. The three-dimensional structures of avian and mammalian CBGs are highly conserved, but the steroid-binding site topographies and their modes of binding steroids differ. Given that CBG serves as the primary transporter of both GCs and reproductive hormones in birds, we aim to review the biological properties of avian CBGs in the context of steroid hormone transportation, stress responses and adaptation to harsh environments, and to provide insight into evolutionary adaptations in CBG functions occurred to accommodate physiological and endocrine changes in birds compared with mammals.

Downregulation of mitochondrial function in adipose tissue is considered as one important driver for the development of obesity-associated metabolic disorders. Inorganic Pyrophosphatase 1 (PPA1) is an enzyme catalyzes the hydrolysis of PPi to Pi, and is required for anabolism to take place in cells. Although alternation of PPA1 has been related to some diseases, the importance of PPA1 in metabolic syndromes has never been discussed before. In this study, we found that global PPA1 knockout mice (PPA1+/-) showed impaired glucose tolerance and severe insulin resistance under HFD feeding. In addition, impaired adipose tissue development and ectopic lipid accumulation were also observed. Conversely, overexpression of PPA1 in adipose tissue by AAV injection can partly reverse the metabolic disorders in PPA1+/- mice, suggesting that impaired adipose tissue function is responsible for the metabolic disorders observed in PPA1+/- mice. Mechanistic studies revealed that PPA1 acted as a PPARγ target gene to maintain mitochondrial function in adipocytes. Furthermore, specific knockdown of PPA1 in fat body of Drosophila led to impaired mitochondria morphology, decreased lipid storage, and made Drosophila more sensitive to starvation. In conclusion, for the first time, our findings demonstrated the importance of PPA1 in maintaining adipose tissue function and whole body metabolic homeostasis.

Brain tissues that are severely damaged by traumatic brain injury (TBI) is hardly regenerated, which leads to a cavity or a repair with glial scarring. Stem-cell therapy is one viable option to treat TBI-caused brain tissue damage, whose use is, whereas, limited by the low survival rate and differentiation efficiency of stem cells. To approach this problem, we developed an injectable hydrogel using imidazole groups-modified gelatin methacrylate (GelMA-imid). In addition, polydopamine (PDA) nanoparticles were used as carrier for stromal-cell derived factor-1 (SDF-1α). GelMA-imid hydrogel loaded with PDA@SDF-1α nanoparticles and human amniotic mesenchymal stromal cells (hAMSCs) were injected into the damaged area in an in-vivo cryogenic injury model in rats. The hydrogel had low module and its average pore size was 204.61 ± 41.41 nm, which were suitable for the migration, proliferation and differentiation of stem cells. In-vitro cell scratch and differentiation assays showed that the imidazole groups and SDF-1α could promote the migration of hAMSCs to injury site and their differentiation into nerve cells. The highest amount of nissl body was detected in the group of GelMA-imid/SDF-1α/hAMSCs hydrogel in the in-vivo model. Additionally, histological analysis showed that GelMA-imid/SDF-1α/hAMSCs hydrogel could facilitate the regeneration of regenerate endogenous nerve cells. In summary, the GelMA-imid/SDF-1α/hAMSCs hydrogel promoted homing and differentiation of hAMSCs into nerve cells, and showed great application potential for the physiological recovery of TBI., Graphical abstract Image 1, Highlights • An injectable imidazole-functionalized GelMA hydrogel loaded with hAMSC and SDF-1α developed to reduce brain injury. • SDF-1α can promote the migration of hAMSCs to injury site and directionally differentiation into nerve cells. • The prepared hydrogels could promote the regeneration and functional reconstruction of brain tissue in vivo

Phosphorylated peptide from Antarctic krill (P-AKP) was prepared by the dry-heating method with sodium pyrophosphate in order to improve its antioxidant activity and osteogenic activity. P-AKP exhibited more competitive DPPH• and OH• scavenging activities compared to the native Antarctic krill peptide (AKP). In hydrogen peroxide (H2O2)-induced oxidative damage of MC3T3-E1 cells, both AKP and P-AKP pretreatment could dose-dependently improve superoxide dismutase (SOD) and catalase (CAT) activities through attenuating the accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA) production. Moreover, AKP and P-AKP prevented oxidative stress-induced down regulation of alkaline phosphatase (ALP) activity and matrix mineralization. Particularly, the promoting effects of P-AKP on the enzymatic antioxidant defense system, differentiation and mineralization was higher than that of AKP. These results suggested that phosphorylation might be a promising approach to improve the antioxidant and osteogenic activity of AKP, and P-AKP could be a beneficial agent for attenuating oxidative stress-related bone loss.

Ovarian cancer is a kind of gynecological malignancy with high mortality. Ferroptosis is a new type of iron-dependent cell death characterized by the formation of lipid peroxides and excessive accumulation of reactive oxygen species. Studies have shown that ferroptosis modulates tumor genesis, progression, and invasion, including ovarian cancer. Based on the mRNA expression data from TCGA, we construct a scoring system using consensus clustering analysis, univariate Cox regression analysis, and least absolute selection operator. Then, we systematically evaluate the relationship between score and clinical characteristics of ovarian cancer. The result from the prediction of biofunction pathways shows that score serves as an independent prognostic marker for ovarian cancer and affects tumor progression by modulating tumor metastasis. Moreover, immunocytes such as activated CD4 T cell, activated CD8 T cell, regulatory T cells, macrophage, and stromal cells, including adipocytes, epithelial cells, and fibroblast infiltrate more in the tumor microenvironment in a high-score group, indicating ferroptosis can also affect tumor immune landscape. Critically, four potentially sensitive drugs, including staurosporine, epothilone B, DMOG, and HG6-64-1 based on the scores, are predicted, and DMOG is recognized as a novel targeted drug for ovarian cancer. In general, we construct the scoring system based on ferroptosis-related genes that can predict the prognosis of ovarian cancer patients and propose that ferroptosis may affect ovarian cancer progression by mediating tumor metastasis and immune landscape. Novel drugs to target ovarian cancer are also predicted.

The demand for American ginseng, a famous traditional medicine and high-grade healthy food, has increased dramatically over recent years. However, only the main root is popular among consumers, whereas other parts of American ginseng are rarely available in the market. In this study, the contents of 5 major ginsenosides (Re, Rc, Rg1, Rd, and Rb1) were determined through high-performance liquid chromatography. Our study showed that all these 5 major ginsenosides are found in different parts of American ginseng plants, and the total content in different parts varied significantly in the following order: fibrous root > flower > branch root > main root > leaf > stem . Interestingly, the total content in the fibrous root was approximately 2.24 times higher than that in the main root. Further research indicated that the ginsenoside content in American ginseng with abnormal characteristics (physical deformity caused by disease and discolouration) is similar to that in the normal plant. Interestingly, a positive correlation was observed between the main root diameter and total ginsenoside content, whereas a negative correlation was observed between the main root length and total ginsenoside content. Our comprehensive study revealed that all parts of American ginseng, including the main root with abnormal characteristics, possess medicinal or economic value. Therefore, our results provide feasible evidence to further explore the potential application of American ginseng.

A rapid wound healing is beneficial for not only recovering esthetics but also reducing pain, complications and healthcare burdens. For such a purpose, continuous efforts have been taken to develop viable dressing material. Acellular dermal matrix (ADM) paste has been used to repair burn wounds and is shown to promote angiogenesis as well as fibroblast attachment and migration. However, its efficacy still needs to be significantly improved to meet clinical demands for accelerating acute skin wound healing. To approach this problem, we studied the added value of a human salivary peptide — Histatin 1 (Hst1). Hst1 was chosen because of its potency to promote the adhesion, spreading, migration, metabolic activity and cell-cell junction of major skin cells and endothelial cells. In this study, we hypothesized that ADM paste and Hst1 showed a better effect on the healing of surgically created acute skin wounds in mice since ADM paste may act as a slow release system for Hst1. Our results showed that the healing efficacy of 10 μM topically administrated Hst1 was significantly higher compared to the control (no Hst1, no ADM) from day 3 to day 10 post-surgery. In contrast, ADM alone failed in our system at all time points. Also, the combination of ADM paste and Hst1 did not show a better effect on percentage of wound healing. Histological analysis showed that 10 μM Hst1 was associated with maximal thickness of newly formed epidermal layer on day 7 as well as the largest collagen area on day 14. In addition, immunohistochemical staining showed that the number of CD31-positive blood vessels in the group of 10 μM Hst1 was 2.3 times compared to the control. The vascular endothelial growth factor (VEGF) expression in the groups of 10 μM Hst1 group and ADM + 10 μM Hst1 group was significantly higher compared with the control group. Furthermore, 10 μM Hst1 group was associated with significantly lower levels of CD68-positive macrophage number, interleukin-1β (IL-1β) expression and C-reactive protein (CRP) expression than those of the other groups (control, ADM alone and ADM + 10 μM Hst1). In contrast, ADM was only associated with significantly lower CD68-positive macrophage number and IL-1β expression in comparison with the control. The co-administration of Hst1 and ADM paste did not yield more beneficial effects than Hst1 alone. In conclusion, the topically administrated of 10 μM Hst1 could be a promising alternative dressing in managing acute wound healing.

Background The aim of the present study was to investigate whether painless labor with patientcontrolled epidural analgesia (PCEA) has a protective effect on pelvic floor function. And to observe if there was any difference in the effect of painless labor with PCEA versus vaginal delivery on postpartum shortterm pelvic floor function. Methods All women who delivered at the hospital's obstetric department during June 2016 to October 2018 were included in the study. They were divided according to delivery mode: painless labor with PCEA [group A (observation group), n=27], and vaginal delivery [group B (control group), n=36]. Pelvic floor function was assessed at postpartum 7 weeks. Results Groups A and B showed no significant difference in the total score at postpartum 6-8 weeks. However, group A showed lower pelvic floor muscle tone at rest and significantly higher muscle strength scores than group B. Both the pre-rest and post-rest phase muscle strength was stronger than in group B (P=0.039 and P=0.016, respectively). There was no significant difference in pelvic floor muscle strength between analgesia and non-analgesia groups, or between episiotomy and non-episiotomy recipients. Conclusions Painless labor with PCEA reduced both pain during the delivery and injury to the pelvic floor. It had protective effect on the pelvic floor muscles.

Obesity is associated with chronic inflammation that exacerbates insulin resistance and metabolic disease. Inflammation drives the pathogenesis of nonalcoholic fatty liver disease (NAFLD), hepatic manifestations of obesity. Hepatic inflammatory microenvironments are believed to induce reprogramming of metabolic pathways; however, intracellular molecules coupling inflammation to metabolism remain poorly understood. Cytokines, damage-associated (DAMPs) and pathogen-associated molecular patterns (PAMPs) are known to activate Traf family members that in turn activate the NF-κB and other inflammatory pathways. We previously reported that hepatic Traf2 and Traf3 augment hepatic glucose production. Here, we demonstrate that hepatocyte Traf2, Traf3 and Traf6 act in concert to promote liver steatosis and insulin resistance. We ablated hepatocyte Traf2, Traf3, and Traf6 individually and in combination (Traf2,3,6Δhep) in adult Traf2flox/flox, Traf3flox/flox, Traf6flox/flox, and Traf2,3,6flox/flox mice, respectively, using AAV-TBG-Cre vectors. Metabolic abnormality was more severe in Traf2,3,6Δhep mice relative to Traf2Δhep, Traf3Δhep and Traf6Δhep mice. Remarkably, Traf2,3,6Δhep mice were resistant to high fat diet-induced liver steatosis, insulin resistance, and glucose intolerance. Hepatic PPARα, a master regulator of fatty acid β oxidation, was substantially elevated in Traf2,3,6Δhep mice. Conversely, in primary hepatocytes, overexpression of Traf3 markedly decreased PPARα stability and protein levels. Traf3 coimmunoprecipitated with PPARα and decreased PPARα transcriptional activity. In primary hepatocytes, ablation of Traf2, Traf3 and Traf6 significantly increased fatty acid β oxidation, and overexpression of Traf3 had the opposite effects. Together, our results unveil an unrecognized hepatocyte Traf/PPARα/fatty acid β oxidation pathway that couples inflammation to liver steatosis and insulin resistance in obesity. Disclosure Z. Zhang: None. H. Lin: None. X. Zhong: None. L. Rui: None.

Skeletal muscle plays a central role in regulating glucose uptake and body metabolism; however, highland hypoxia is a severe challenge to aerobic metabolism in small endotherms. Therefore, understanding the physiological and genetic convergence of muscle hypoxia tolerance has a potential broad range of medical implications. Here we report and experimentally validate a common physiological mechanism across multiple high-altitude songbirds that improvement in insulin sensitivity contributes to glucose homeostasis, low oxygen consumption, and relative activity, and thus increases body weight. By contrast, low-altitude songbirds exhibit muscle loss, glucose intolerance, and increase energy expenditures under hypoxia. This adaptive mechanism is attributable to convergent missense mutations in the BNIP3L gene, and METTL8 gene that activates MEF2C expression in highlanders, which in turn increases hypoxia tolerance. Together, our findings from wild high-altitude songbirds suggest convergent physiological and genetic mechanisms of skeletal muscle in hypoxia resistance, which highlights the potentially medical implications of hypoxia-related metabolic diseases., Author summary We integrate physiological, genomic and functional experimental methods to illustrate the convergent molecular and genetic mechanisms of hypoxia resistance in wild songbirds. We find that highland native songbirds have greater body and muscle mass with an increase in insulin sensitivity and aerobic metabolism comparing to lowland songbirds. Comparative transcriptomes and functional experiments show that MEF2C is a shared overexpression gene in highland songbirds and maintains muscle mass and insulin sensitivity in hypoxia. Genetically, four genes with high genetic divergence between altitudinal tree sparrows have convergent nonsynonymous substitutions in snow finches and three of these are related with hypoxia including HBB, BNIP3L and METTL8. METTL8 may regulate the expression of MEF2C and thus increase muscle hypoxia resistance. These results uncover the physiological and genetic convergence on muscle hypoxia resistance in highland songbirds, and support novel and valuable insights into highland adaptation.

Objectives Protease-activated receptor (PAR) 1 and PAR2 have been implicated in RA, however their exact role is unclear. Here, we detailed the mechanistic impact of these receptors on the onset and development of inflammatory arthritis in murine CIA and antigen-induced arthritis (AIA) models. Methods CIA or AIA was induced in PAR1 or PAR2 gene knockout (KO) and matched wild type mice. The onset and development of arthritis was monitored clinically and histologically. Immune cells, cytokines and MMPs were detected by ELISA, zymography, flow cytometry, western blot or immunohistochemistry. Results In CIA, PAR1KO and PAR2KO exacerbated arthritis, in opposition to their effects in AIA. These deficient mice had high plasma levels of IL-17, IFN-γ, TGF-β1 and MMP-13, and lower levels of TNF-α; T cells and B cells were higher in both KO spleen and thymus, and myeloid-derived suppressor cells were lower only in PAR1KO spleen, when compared with wild type cells. Th1, Th2 and Th17 cells were lower in PAR1KO spleens cells, whereas Th1 and Th2 cells were lower and Th17 cells higher in both KO thymus cells, when compared with wild type cells. PAR1KO synovial fibroblasts proliferated faster and produced the most abundant MMP-9 amongst three type cells in the control, lipopolysaccharides or TNF stimulated conditions. Conclusion This is the first study demonstrated that deficiency of PAR1 or PAR2 aggravates inflammatory arthritis in CIA. Furthermore, the protective functions of PAR1 and PAR2 in CIA likely occur via differing mechanisms involving immune cell differentiation and cytokines/MMPs.

Cell‐based bone tissue engineering techniques utilize both osteogenic cells and biomedical materials, and have emerged as a promising approach for large‐volume bone repair. The success of such techniques is highly dependent on cell adhesion, spreading, and osteogenic activities. In this study, we investigated the effect of co‐administration of all‐trans retinoic acid (ATRA) and human salivary peptide histatin‐1 (Hst1) on the spreading and osteogenic activities of pre‐osteoblasts on bio‐inert glass surfaces. Pre‐osteoblasts (MC3T3‐E1 cell line) were seeded onto bio‐inert glass slides in the presence and absence of ATRA and Hst1. Cell spreading was scored by measuring surface areas of cellular filopodia and lamellipodia using a point‐counting method. The distribution of fluorogenic Hst1 within osteogenic cells was also analyzed. Furthermore, specific inhibitors of retinoic acid receptors α, β, and γ, such as ER‐50891, LE‐135, and MM‐11253, were added to identify the involvement of these receptors. Cell metabolic activity, DNA content, and alkaline phosphatase (ALP) activity were assessed to monitor their effects on osteogenic activities. Short‐term (2 h) co‐administration of 10 μm ATRA and Hst1 to pre‐osteoblasts resulted in significantly higher spreading of pre‐osteoblasts compared to ATRA or Hst1 alone. ER‐50891 and LE‐135 both nullified these effects of ATRA. Co‐administration of ATRA and Hst1 was associated with significantly higher metabolic activity, DNA content, and ALP activity than either ATRA or Hst1 alone. In conclusion, co‐administration of Hst1 with ATRA additively stimulated the spreading and osteogenicity of pre‐osteoblasts on bio‐inert glass surfaces in vitro., Adhesion and spreading of osteogenic cells are indispensable for initiation of bone regeneration. We showed that the co‐administration of all‐trans retinoic acid (ATRA) and human salary histatin‐1 (Hst1) resulted in significantly enhanced spreading, metabolic activity, proliferation (DNA content), and osteogenic differentiation (alkaline phosphatase activity) of pre‐osteoblasts on bio‐inert surfaces, thus bearing a promising application potential in bone tissue engineering.

The association between whole blood viscosity (WBV) and metabolic syndrome (MetS) is still scarcely investigated in the population-based prospective cohort. We aim to explore the longitudinal effect of WBV on MetS, and to verify whether WBV measures can be used as early predictors for MetS. The longitudinal cohort consisted of 3,508 adults (2,350 males and 1,158 females) who visited the health check-up system twice. WBV were measured at four shear rate (200, 50, 10 and 1 s-1), and their values were classified into quartiles. Multivariate Cox models were used to estimate the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) in men and women, respectively. A total of 444 (12.66%) incident MetS were observed at follow-up period. The incidences of MetS significantly increased with increasing quartiles of WBVs at all of the shear rate in men. After adjusting for baseline age, smoking, obesity, hypertension, hyperglycemia, and hyperlipidemia status, all of the WBV measures were significantly associated with incident MetS in men, and the HRs showed clear increasing trend across the quartiles of baseline WBVs. There were no significant association between WBVs and incident MetS in women. These findings suggest that MetS has a hemodynamic basis, and WBVs could be used as independent early predictor for MetS in men.

STUDY QUESTION Does an artificially induced FSH surge at the time of hCG trigger improve IVF/ICSI outcomes? SUMMARY ANSWER An additional FSH bolus administered at the time of hCG trigger has no effect on clinical pregnancy rate, embryo quality, fertilization rate, implantation rate and live birth rate in women undergoing the long GnRH agonist (GnRHa) protocol for IVF/ICSI. WHAT IS KNOWN ALREADY Normal ovulation is preceded by a surge in both LH and FSH. Few randomized clinical trials have specifically investigated the role of the FSH surge. Some studies indicated that FSH given at hCG ovulation trigger boosts fertilization rate and even prevents ovarian hyperstimulation syndrome (OHSS). STUDY DESIGN, SIZE, DURATION This was a randomized, double-blinded, placebo-controlled trial conducted at a single IVF center, from June 2012 to November 2013. A sample size calculation indicated that 347 women per group would be adequate. A total of 732 women undergoing IVF/ICSI were randomized, using electronically randomized tables, to the intervention or placebo groups. Participants and clinical doctors were blinded to the treatment allocation. PARTICIPANTS/MATERIALS, SETTING, METHODS Patients aged ≤42 years who were treated with IVF/ICSI owing to tubal factor, male factor, unexplained, endometriosis and multiple factors were enrolled in this trial. Subjects all received a standard long GnRHa protocol for IVF/ICSI and hCG 6000–10 000 IU to trigger oocyte maturation. A total of 364 and 368 patients were randomized to receive a urinary FSH (uFSH) bolus (6 ampules, 450 IU) and placebo, respectively, at the time of the hCG trigger. The primary outcome measure was clinical pregnancy rate. The secondary outcome measures were FSH level on the day of oocyte retrieval, number of oocytes retrieved, good-quality embryo rate, live birth rate and rate of OHSS. MAIN RESULTS AND THE ROLE OF CHANCE There were no significant differences in the baseline demographic characteristics between the two study groups. There were also no significant differences between groups in cycle characteristics, such as the mean number of stimulation days, total gonadotrophin dose and peak estradiol. The clinical pregnancy rate was 51.6% in the placebo group and 52.7% in the FSH co-trigger group, with an absolute rate difference of 1.1% (95% CI −6.1% to 8.3%). The number of oocytes retrieved was 10.47 ± 4.52 and 10.74 ± 5.01 (P = 0.44), the rate of good-quality embryos was 37% and 33.9% (P = 0.093) and the implantation rate was 35% and 36% (P = 0.7) in the placebo group and the FSH co-trigger group, respectively. LIMITATIONS, REASONS FOR CAUTION This was a single-center study, which may limit its effectiveness. The use of uFSH is a limitation, as this is not the same as the natural FSH. We did not collect follicular fluid for further study of molecular changes after the use of uFSH as a co-trigger. WIDER IMPLICATIONS OF THE FINDINGS Based on previous data and our results, an additional FSH bolus administered at the time of hCG trigger has no benefit on clinical pregnancy rates in women undergoing the long GnRHa protocol in IVF/ICSI: a single hCG trigger is sufficient. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by the National Key Research and Development Program of China (2016YFC1000205); Sun Yat-Sen University Clinical Research 5010 Program (2016004); the Science and Technology Project of Guangdong Province (2016A020216011 and 2017A020213028); and Science Technology Research Project of Guangdong Province (S2011010004662). There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER The trial was registered in the Chinese Clinical Trial Registry (ChiCTR-TRC-12002246). TRIAL REGISTRATION DATE 20 May 2012. DATE OF FIRST PATIENT’S ENROLMENT 10 June 2012.

Background Preclinical studies indicate iron deficiency (ID) plays an important role in cardiac remodelling. However, the relationship between ID and cardiac remodelling remains unknown in clinical setting. This retrospective study aims to identify a potential biomarker for the myocardial remodelling in patients with ID. Due to limited patients with ID are identified without iron deficiency anaemia (IDA), we analyse the relationship of total iron binding capacity (TIBC) and the left ventricular mass index (LVMI) in patients with iron deficiency anaemia. Methods A total of 82 patients with IDA exhibiting the diagnostic criteria for IDA were enrolled in the study. Among the patients, 65 had reported LVMI values. Subsequently, these patients were divided into two groups according to abnormal LVMI (> 115 g/m2 in men and > 95 g/m2 in women). Linear bivariate analysis was performed to detect the associations of haemoglobin or TIBC with clinical and echocardiographic characteristics. Simple linear regression analysis was used to evaluate the correlation between LVMI and the parameters of IDA, while multivariable linear analysis was used to assess the association of LVMI with age, TIBC and haemoglobin. Logistic regression analysis was utilized to determine the relationship of LV remodelling with anaemia severity and TIBC. Results As compared with control group, the levels of TIBC in abnormal LVMI group are increased. Using log transformed LVMI as the dependent variable, simultaneously introducing age, TIBC, and haemoglobin into the simple linear regression or multivariable linear regression analysis confirmed the positive association among these factors. Bivariate correlation analysis reveals the irrelevance between haemoglobin and TIBC. In logistic regression analysis, TIBC is associated with the risk of LV remodelling. Conclusions Results of study indicate that TIBC exhibit an explicit association with LVMI in patients with iron deficiency anaemia. Logistic analysis further confirms the contribution of TIBC to abnormal LVMI incidence among this population with IDA.

Hepatic steatosis is the early stage of alcoholic liver disease (ALD), may progress to steatohepatitis, fibrosis even cirrhosis. Polydatin, the primary active component of Polygonum cuspidatum Sieb. et Zucc, has been recognized to possess hepatoprotective and anti-inflammatory properties. To investigate whether polydatin alleviates ethanol induced liver injury and to elucidate the underlying molecular mechanisms, zebrafish larvae at 4 days post-fertilization (dpf) were exposed to 350 mmol/L of ethanol for 32 h, then treated with polydatin for 48 h. Oil red O, Nile Red and H&E staining were used to analyze the pathological changes in liver. The mRNA levels were measured by quantitative PCR and the antioxidant capacity was detected using H2O2-specific fluorescent probe. Here, polydatin strongly alleviated hepatic steatosis and decreased the expression levels of alcohol and lipid metabolism-related genes, including CYP2Y3, CYP3A65, HMGCRa, HMGCRb and FASN. Additionally, polydatin inhibited oxidative stress in the liver according to fluorescent probe. Moreover, significantly up-regulated expression of DNA damage-related genes (CHOP, GADD45αa) revealed that polydatin attenuated hepatic apoptosis in larvae. In conclusion, polydatin may improve the liver function of zebrafish with acute alcoholic liver injury through attenuating hepatic fat accumulation, ameliorating lipid and ethanol metabolism and reducing oxidative stress and DNA damage. Keywords: Alcoholic liver disease, Polydatin, Zebrafish, Oxidative stress, Lipid metabolism

Central obesity (CO) is a defining characteristic of polycystic ovary syndrome (PCOS) and PCOS-induced disorders are likely to be exacerbated in the presence of CO. This study aims to evaluate the impact of CO on infertile women with PCOS undergoing in vitro fertilization (IVF).It is a retrospective and case–control study. One hundred eighty-eight infertile PCOS women undergoing IVF were divided into CO group (n = 70, waist circumference [WC] ≥80 cm) and noncentral obesity (NCO) group (n = 118, WC

While wound therapy remains a clinical challenge in current medical practice, much effort has focused on developing biological therapeutic approaches. This paper presents a comprehensive review of delivery systems for current biologicals for the treatment of chronic wounds and severe burns. The biologicals discussed here include proteins such as growth factors and gene modifying molecules, which may be delivered to wounds free, encapsulated, or released from living systems (cells, skin grafts or skin equivalents) or biomaterials. Advances in biomaterial science and technologies have enabled the synthesis of delivery systems such as scaffolds, hydrogels and nanoparticles, designed to not only allow spatially and temporally controlled release of biologicals, but to also emulate the natural extracellular matrix microenvironment. These technologies represent an attractive field for regenerative wound therapy, by offering more personalised and effective treatments.