Combinational strategy using albumin-based nanoparticles to enable synergetic anti-rheumatic efficacy and reduced hepatotoxicity.

Methotrexate (MTX) is recognized as the golden standard for rheumatoid arthritis (RA) treatment. However, it can cause liver damage in long-term application. Although nanomedicines can target to inflamed sites, most of them tend to accumulate in liver. Glycyrrhizinic acid (GA) holds potential to reverse MTX-associated hepatotoxicity. The combination of GA and MTX might achieve a synergistic anti-inflammatory efficacy and reduced hepatotoxicity. As MTX and GA have totally different in vivo performance, it is necessary to co-encapsulate them in one carrier to coordinate their in vivo fates. Here, we co-delivered MTX and GA to arthritic joints using a human serum albumin-based nanoparticle (HSN). We found the dual drug-loaded albumin nanoparticles (HSN/MTX/GA) could preferentially distribute in inflamed joints, where GA can extend MTX retention by inhibiting the expression of efflux pumps for MTX, thereby exerting synergistic therapeutic effect. In liver tissues, GA was able to reverse the MTX-induced liver damage by activating anti-oxidant defense Nrf2/HO-1 and anti-apoptosis Bcl-2/Bax signaling. We offer a combinational strategy to effectively overcome the MTX-induced hepatotoxicity and enhance the anti-rheumatic efficacy simultaneously. Furthermore, we verified the underlying mechanism about how GA cooperated with MTX in vivo for the first time. Our findings can provide valuable insights for long-term treatment of RA.

Isolation, identification and transcriptome analysis of triadimefon-degrading strain Enterobacter hormaechei TY18.

Triadimefon, a type of triazole systemic fungicide, has been extensively used to control various fungal diseases. However, triadimefon could lead to severe environmental pollution, and even threatens human health. To eliminate triadimefon residues, a triadimefon-degrading bacterial strain TY18 was isolated from a long-term polluted site and was identified as Enterobacter hormaechei. Strain TY18 could grow well in a carbon salt medium with triadimefon as the sole nitrogen source, and could efficiently degrade triadimefon. Under triadimefon stress, a total of 430 differentially expressed genes (DEGs), including 197 up-regulated and 233 down-regulated DEGs, were identified in strain TY18 using transcriptome sequencing (RNA-Seq). Functional classification and enrichment analysis revealed that these DEGs were mainly related to amino acid transport and metabolism, carbohydrate transport and metabolism, small molecule and pyrimidine metabolism. Interestingly, the DEGs encoding monooxygenase and hydrolase activity acting on carbon-nitrogen were highly up-regulated, might be mainly responsible for the metabolism in triadimefon. Our findings in this work suggest that strain E. hormaechei TY18 could efficiently degrade triadimefon for the first time. They provide a great potential to manage triadimefon biodegradation in the environment successfully.

Normal weight obesity is associated with lower AFC and adverse IVF outcomes.

Background: Body weight could be classified into underweight, normal weight and overweight according to percentage of body fat (%BF), and normal weight obesity (NWO) is defined as a normal BMI but a high %BF. While the impact of NWO in women fecundity remain unknow. Therefore, this study aimed to investigate the associations between %BF and reproductive outcomes among in vitro fertilization (IVF) women with normal BMI. Methods: A total of 469 women were included in this study and were classified into low %BF, normal %BF and high %BF according to previous study. Multivariate generalized regression models were employed to evaluate the associations of %BF with ovarian reserve parameters, IVF outcomes and early pregnancy outcomes. We further run sensitivity analyses by restricted the analysis to young women and those only with tubal factor, respectively. Results: About 32.2% of normal BMI women were misclassified according %BF, with 16.4% of them were low %BF and 15.8% were high %BF. The high %BF group had significantly lower antral follicle count (AFC) than normal %BF groups, and the AFC showed a tendency of decrease as %BF increased. In sensitivity analysis in young women, high %BF group also had significantly lower number of good-quality embryos when compared to normal %BF groups. The results expanded to all IVF outcomes when analysis restricted to tubal factor women. Conclusion: In summary, misclassifications of body weight status based on BMI are common according to %BF, and NWO is associated with adverse reproductive outcomes.

Er:YAG Laser Therapy on Alveolar Osteitis After Mandibular Third Molar Surgery: A Randomized Controlled Clinical Study.

Background: Alveolar osteitis (AO) or "dry socket" affects the quality of life of patients, and there is a high clinical demand for its effective treatment. Objective: To evaluate the effect of Er:YAG laser therapy (ErLT) on AO after mandibular third molar surgery. Methods: Eighty-three patients were randomly divided into Er (n = 43) and control groups (n = 40). In the Er group, the Er:YAG laser (2940 nm; AT Fidelis Fotona, Ljubljana, Slovenia) was used to irradiate the AO site directly in micro short-pulsed mode (pulse duration 0.1 ms, pulse energy 100 mJ, frequency 40 Hz, water 4, and air 2) until all debris and necrotic material had been removed, exposing fresh bone and soft tissue surfaces with blood exudation. The control group received mechanical therapy until the treated lesions resembled those in the Er group. Pain assessment was performed at baseline and on days 1-7 post-intervention using the visual analog scale (VAS). Wound healing was assessed using the wound healing index (WHI). The operating times of the two therapies were also recorded. Results: Group Er had lower VAS scores than the control group on days 1-3 (p = 0.00). There was no significant difference between the two groups on days 4-7 (p = 0.15). The WHI scores were better in the Er group than those in the control group (t = 2.65, p = 0.01), especially in terms of redness (t = 2.70, p = 0.01). There was no significant difference in the operating time between the two groups (t = 0.76, p = 0.45). Conclusions: Compared with mechanical therapy, ErLT for AO provides rapid pain relief and improved wound healing.

Advances in mesenchymal stem cells therapy for tendinopathies.

Tendinopathies are chronic diseases of an unknown etiology and associated with inflammation. Mesenchymal stem cells (MSCs) have emerged as a viable therapeutic option to combat the pathological progression of tendinopathies, not only because of their potential for multidirectional differentiation and self-renewal, but also their excellent immunomodulatory properties. The immunomodulatory effects of MSCs are increasingly being recognized as playing a crucial role in the treatment of tendinopathies, with MSCs being pivotal in regulating the inflammatory microenvironment by modulating the immune response, ultimately contributing to improved tissue repair. This review will discuss the current knowledge regarding the application of MSCs in tendinopathy treatments through the modulation of the immune response.

Transcription Factor GLI1 Induces IL-6-Mediated Inflammatory Response and Facilitates the Progression of Adamantinomatous Craniopharyngioma.

Adamantinomatous craniopharyngioma (ACP) is a neuroendocrine tumor whose pathogenesis remains unclear. This study investigated the role of glioma-associated oncogene family zinc finger 1 (GLI1), a transcription factor in the sonic hedgehog (SHH) signaling pathway, in ACP. We discovered that GLI1 regulates the expression of IL-6, thereby triggering inflammatory responses in ACP and influencing the tumor's progression. Analyzing the Gene Expression Omnibus (GEO) database chip GSE68015, we found that GLI1 is overexpressed in ACP, correlating positively with the spite of ACP and inflammation markers. Knockdown of GLI1 significantly inhibited the levels of tumor necrosis factor α, interleukin-6 (IL-6), and IL-1ß in ACP cells, as well as cell proliferation and migration. We further identified a binding site between GLI1 and the promoter region of IL-6, demonstrating that GLI1 can enhance the expression of IL-6. These findings were verified in vivo, where activation of the SHH pathway significantly promoted GLI1 and IL-6 expressions in nude mice, inducing inflammation and tumor growth. Conversely, GLI1 knockdown markedly suppressed these processes. Our study uncovers a potential molecular mechanism for the occurrence of inflammatory responses and tumor progression in ACP.

Nd:YAG laser therapy on postoperative pain, swelling, and trismus after mandibular third molar surgery: a randomized double-blinded clinical study.

This study aims to evaluate the effect of Nd:YAG laser therapy (NdLT) on postoperative pain, swelling, and trismus after mandibular third molar (M3) surgery. Three hundred patients were randomly divided into the Nd group (n = 100), medication group (n = 100), and Nd+medication (Nd+m) group (n = 100). The WHARFE classification system was used to assess surgical difficulty. After surgery, the Nd group was irradiated by the Nd:YAG laser in very long-pulsed mode (VLP, pulse duration 1 ms, 20 Hz, 4 W, R21-C3) in 6 regions of the extraction socket with a total energy of 300 J. For the medication group, dexamethasone 0.75 mg and loxoprofen 60 mg were prescribed immediately and every 12 h thereafter for 3 days. The Nd+m group received both treatments mentioned above. Pain assessment was performed at 6, 24, 48, and 72 h postoperatively using the visual analog scale (VAS). Swelling was evaluated by changes in the distance from (1) the tragus to the labial commissure, (2) the tragus to the pogonion, and (3) the mandibular angle to the lateral canthus preoperatively and 72 h postoperatively. Trismus was assessed by the change in maximum mouth opening. Groups Nd and Nd+m had lower VAS scores at 6 h, 24 h, and 48 h (F = 13.80, p = 0.00), but the difference between the two groups was not significant (F = 1.34, p = 0.11). However, no significant difference was observed at 72 h (p = 0.10). There was no significant difference in swelling or trismus among the three groups (p > 0.05). NdLT is an effective approach to improve complications after M3 surgery.

Comparison of Cumulative Live Birth Rates Between Progestin and GnRH Analogues in Preimplantation Genetic Testing Cycles.

CONTEXT: Progestins have recently been used as an alternative for gonadotropin-releasing hormone (GnRH) analogues to prevent premature luteinizing hormone surge due to the application of vitrification technology. However, the long-term efficacy and safety of a progestin-primed ovarian stimulation (PPOS) regimen, including oocyte competence, cumulative live birth rate (LBR), and offspring outcomes, remain to be investigated. OBJECTIVE: To compare cumulative LBR of preimplantation genetic testing (PGT) cycles between a PPOS regimen and GnRH analogues. METHODS: This was a retrospective cohort study at a tertiary academic medical center. A total of 967 patients with good prognosis were categorized into 3 groups, of which 478 patients received a long GnRH agonist, 248 patients received a GnRH antagonist, and 250 received a PPOS regimen. Medroxyprogesterone 17-acetate was the only progestin used in the PPOS regimen. The primary outcome was cumulative LBR. Secondary outcomes included time to live birth, cumulative rates of biochemical and clinical pregnancy and pregnancy loss, and perinatal outcomes. RESULTS: The PPOS regimen was negatively associated with cumulative LBR compared with GnRH antagonists and GnRH agonists (28.4% vs 40.7% and 42.7%). The average time to live birth was significantly shorter with GnRH antagonists than with the PPOS regimen. The cumulative biochemical and clinical pregnancy rates were also lower in the PPOS regimen than GnRH analogues, while cumulative pregnancy loss rates were similar across groups. Furthermore, the number and ratio of good-quality blastocysts were significantly reduced in the PPOS regimen compared with GnRH analogues. In addition, perinatal outcomes were comparable across 3 groups. CONCLUSION: A PPOS regimen may be adversely affect cumulative LBR and blastocyst quality in women with good prognosis compared with GnRH analogues in PGT cycles.

Association between serum LH levels on hCG trigger day and live birth rate after fresh embryo transfer with GnRH antagonist regimen in different populations.

Objective: To investigate whether serum LH levels on hCG trigger day are associated with live birth rate (LBR) after fresh embryo transfer with GnRH antagonist regimen in different populations. Methods: This study was a retrospective study. A total of 3059 fresh embryo transfers were divided into three populations: predicted normal ovarian responders (NOR) (n=2049), patients with PCOS (n=533), and predicted poor ovarian responders (POR) (n=477). Each population was stratified into three groups based on LH levels: < 25th percentile, 25-75th percentile, and > 75th percentile. The primary outcome of the study was LBR, and secondary outcomes included implantation, clinical pregnancy, and early pregnancy loss rates. Univariable and multivariable regression analyses were performed to adjust for potential confounders. Results: In NOR, compared to the reference group (>75th percentile), LBR was significantly lower in the < 25th percentile group (adjusted OR=0.662; 95%CI, 0.508-0.863) and 25-75th percentile group (adjusted OR=0.791; 95%CI, 0.633-0.988). In PCOS patients, LBR decreased significantly in the < 25th percentile group (41.4%) compared to the 25-75th percentile group (53.7%) and > 75th percentile group (56.1%). In addition, the LBR was lower in the < 25th percentile group (33.6%) compared with the 25-75th percentile group (43.4%) and the>75th percentile group (42.0%) in POR, but this was not statistically significant. Conclusions: High serum LH levels are associated with increased LBR after fresh embryo transfer in GnRH antagonist cycles, which may be attributable to higher implantation rate. LH may be a predictor of whether to schedule fresh embryo transfer in IVF cycles for better clinical outcomes.

High anti-Mullerian hormone level is adversely associated with cumulative live birth rates of two embryo transfers after the first initiated cycle in patients with polycystic ovary syndrome.

Objective: Anti-Mullerian hormone (AMH) has been recently identified as a potential predictor of live birth rates (LBRs) following assisted reproductive technology (ART) treatment. This study aimed to investigate the association between AMH levels and the outcomes of in vitro fertilization (IVF) in patients with polycystic ovary syndrome (PCOS). Methods: Patients with PCOS initiating their first ovarian stimulation under the gonadotropin-releasing hormone antagonist protocol at the Guangdong Women and Children Hospital, China, were enrolled from November 2014 to September 2018. A total of 157 patients who underwent fresh embryo transfer (ET) cycles were included in group A, whereas 187 patients who underwent frozen-thawed ET cycles were included in group B. After the failure of the first ET cycle, 94 patients underwent the second ET cycle with frozen-thawed embryos. Of these 94 patients, 52 had failed the first fresh ET cycle (group C) and 42 had failed the first frozen-thawed ET cycle (group D). Successful embryo transfer was defined as live birth. This retrospective cohort study addressed the association between AMH levels and pregnancy outcomes using logistic regression approaches. After adjusting for age, body mass index, antral follicle counts, baseline follicle-stimulating hormone levels and baseline progesterone levels, LBRs were compared among the four groups and the cumulative live birth rate after two embryo transfers (TCLBR) was calculated. Results: The LBRs showed no differences among the four groups. Higher serum AMH levels were found to be associated with a lower TCLBR [adjusted OR 0.937 (0.888-0.987), P = 0.015]. In patients who underwent the second ET cycle, LBRs were inversely proportional to AMH levels [crude OR 0.904 (0.828-0.986), P = 0.022 versus adjusted OR 0.845 (0.754-0.946), P = 0.004, respectively]. In addition, the LBR was approximately 61%-78% lower in the group with AMH levels of >12 ng/mL [crude OR 0.391 (0.168-0.912), P = 0.030 versus adjusted OR 0.217 (0.074-0.635), P = 0.005, respectively]. Conclusions: Among PCOS patients high AMH level (>12 ng/ml) is found to be associated with low TCLBR and low LBR of the second embryo transfer cycles. The results provide limited clinical inferences and warrant further investigation.

Comparison of cumulative live birth rates between progestin-primed ovarian stimulation protocol and gonadotropin-releasing hormone antagonist protocol in different populations.

Objective: To compare cumulative live birth rate (LBR) between progestin-primed ovarian stimulation (PPOS) and GnRH antagonist protocols of preimplantation genetic testing (PGT) cycles in different populations. Methods: This was a retrospective cohort study. A total of 865 patients were enrolled and separate analyses were performed for three populations: 498 patients with predicted normal ovarian response (NOR), 285 patients with PCOS, and 82 patients with predicted poor ovarian response (POR). The primary outcome was cumulative LBR for one oocyte retrieval cycle. The results of response to ovarian stimulation were also investigated, including numbers of oocytes retrieved, MII oocytes, 2PN, blastocysts, good-quality blastocysts, and usable blastocysts after biopsy, as well as rates of oocyte yield, blastocyst formation, good-quality blastocysts, and moderate or severe OHSS. Univariable and multivariable logistic regression analyses were used to identify potential confounders that may be independently associated with cumulative live birth. Results: In NOR, the cumulative LBR of PPOS protocol was significantly lower than that of GnRH antagonists (28.4% vs. 40.7%; P=0.004). In multivariable analysis, the PPOS protocol was negatively associated with cumulative LBR (adjusted OR=0.556; 95% CI, 0.377-0.822) compared to GnRH antagonists after adjusting for potential confounders. The number and ratio of good-quality blastocysts were significantly reduced in PPOS protocol compared to GnRH antagonists (2.82 ± 2.83 vs. 3.20 ± 2.79; P=0.032 and 63.9% vs. 68.5%; P=0.021), while numbers of oocytes, MII oocytes and 2PN did not show any significant difference between GnRH antagonist and PPOS protocols. PCOS patients had similar outcomes as NOR. The cumulative LBR of PPOS group appeared to be lower than that of GnRH antagonists (37.4% vs. 46.1%; P=0.151), but not significantly. Meanwhile, the proportion of good-quality blastocysts in PPOS protocol was also lower compared to GnRH antagonists (63.5% vs. 68.9%; P=0.014). In patients with POR, the cumulative LBR of PPOS protocol was comparable to that of GnRH antagonists (19.2% vs. 16.7%; P=0.772). There was no statistical difference in the number and rate of good-quality blastocysts between the two protocols in POR, while the proportion of good-quality blastocysts appeared to be higher in PPOS group compared to GnRH antagonists (66.7% vs. 56.3%; P=0.182). In addition, the number of usable blastocysts after biopsy was comparable between the two protocols in three populations. Conclusion: The cumulative LBR of PPOS protocol in PGT cycles is lower than that of GnRH antagonists in NOR. In patients with PCOS, the cumulative LBR of PPOS protocol appears to be lower than that of GnRH antagonists, albeit lacking statistical difference, whereas in patients with diminished ovarian reserve, the two protocols were comparable. Our findings suggest the need for caution when choosing PPOS protocol to achieve live births, especially for normal and high ovarian responders.

Physiologically-Based Pharmacokinetic Modeling of Tenofovir Disoproxil Fumarate in Pregnant Women.

PURPOSE: Physiological changes during pregnancy can affect antiretroviral drug processes and further influence drug efficacy and safety. Physiologically-based pharmacokinetic (PBPK) modeling offers a unique modality to predict PK in pregnant women. The objective of this study was to establish a PBPK modeling of tenofovir disoproxil fumarate (TDF) in pregnant women, to provide a reference for the clinical use of TDF. METHODS: A full PBPK modeling of tenofovir (TFV) and TDF following i.v. and p.o. administration was developed using the simulation software PK-Sim®. The modeling was then extrapolated to pregnant women based on pregnancy- related physiological parameters in Mobi® Simulator. The mean fold error (MFE) and geometric mean fold error (GMFE) methods were used to compare the differences between predicted and observed values of PK parameters (Cmax, tmax, AUC0-∞) to evaluate the accuracy of PBPK modeling. RESULTS: The developed PBPK modeling successfully predicted the TDF disposition in the non-pregnant population, wherein the MFE average and GMFE of all predicted PK parameters were within a 1.5-fold error range, and more than 96.30% of the predicted drug concentration values were within a 2-fold error range of the measured values. After the extrapolation of these models to the third trimester of pregnancy, the scaling anatomy/physiology and hepatic intrinsic clearance made the pregnant population PBPK modeling meet the standard requirement of 0.5 < MFE and GMFE value < 2. It was more appropriate to simulate the in vivo process of low-dose TDF in pregnant women. CONCLUSION: The non-pregnant population PBPK modeling of TDF established in our study can be extrapolated to pregnant women. Our study provides a reference for realizing clinical personalized medication for pregnant women.

Preimplantation genetic testing for human blastocysts with potential parental contamination using a quantitative parental contamination test (qPCT): an evidence-based study.

RESEARCH QUESTION: Is it possible to develop a quantitative method for detecting parental DNA contamination in conventional IVF using preimplantation genetic testing for aneuploidy (PGT-A)? DESIGN: In this study, a quantification method was established for the parental contamination test (qPCT), which ensured more reliable results, and then verified its effectiveness for vitrified conventional IVF embryos. A total of 120 surplus vitrified blastocysts from patients who underwent prior routine IVF cycles were available for study. RESULTS: The results of the prospective clinical study of qPCT-PGT-A showed that the maternal contamination rate was 0.83% (1/120) and that the risk of paternal contamination was negligible. The 24 frozen embryo transfer cycles resulted in 16 clinical pregnancies, including 13 live births, one late inevitable miscarriage and two ongoing pregnancies. CONCLUSIONS: The risk of PGT in embryos with potential parental contamination is relatively low, and PGT-A is applicable for vitrified conventional IVF embryos.

Letrozole + Ziwu Liuzhu Transcutaneous Electrical Acupoint Stimulation Improves Ovulation-Induced Pregnancy Rate in Obese Women with Polycystic Ovary Syndrome: A Prospective Cohort Study.

Objective: This study investigated the effect of letrozole with/without meridian-infusion percutaneous electrical stimulation on the rates of ovulation-induced pregnancy in patients with obese polycystic ovary syndrome (obPCOS). Materials and Methods: Patients with obPCOS, ages 20-40, each with a body mass index (BMI) ≥24 kg/m2, and/or waist circumference ≥80 cm, and at least 1 side tubal patency were enrolled at the Guangdong Women and Children Hospital, Guangzhou, China. They were divided into 2 groups: ZLT [Ziwu Liuzhu + transcutaneous electrical acupoint stimulation] and control. Baseline conditions and pregnancy status were collected for all patients. Multivariate Cox regression analysis and sensitivity analysis of propensity score matching (PSM) were performed for the groups after multiple interpolations. Results: From July 2021 to September 2022, 345 patients with obPCOS were recruited: 53 cases/69 cycles in the ZLT group and 292 cases/396 cycles in the control group. The 2 sets of baselines were flush. The anovulatory cycle rates were: ZLT, 2.89% (2/69); and control, 1.77% (7/396); P > 0.05. Multifollicle growth-cycle rates were: ZLT, 0% (0/69); and control, 0.76% (3/396); P > 0.05. Multivariate COX regression analysis showed adjusted hazard ratio (aHR) 95% confidence interval (CI): 2.11 (1.19, 3.73); P = 0.011. Multivariate Cox regression analysis with multiple imputation showed aHR 95% CI: 2.11 (1.19, 3.73); P = 0.013. In the overweight group (24-28 kg/m2), the pregnancy rate of the control and ZLT groups were 20.2% and 32.3%, respectively, aHR 95% CI: 1.76 (0.87,3.55); P = 0.113. In the obese cohort (≥ 28 kg/m2), the control and ZLT groups, pregnancy rates were 10.7% and 27.3%, respectively, aHR 95% CI: 3.46 (1.21, 9.92); P = 0.021; (Pfor interaction = 0.369). The caliper value was set as 0.2 for BMI and antral-follicle count, and PSM was performed at 1:1, aHR 95%CI: 2.45 (1.01, 5.96); P = 0.048. Conclusions: Letrazole + ZLT had a positive effect on ovulation-induced pregnancy rates in patients with obPCOS.

Administration of depot GnRH agonist prior to programmed frozen-thawed embryo transfer does not improve the live birth rate in ovulatory women: A large, multi-center retrospective study.

Despite that gonadotropin-releasing hormone (GnRH) agonist pretreatment has been widely used before programmed frozen-thawed transfer (FET), its impact on live birth rates in ovulatory women remains uncertain. In the present study, we aim to determine if GnRH agonists pretreatment before FET improves live birth rates in women undergoing in vitro fertilization with FET. Programmed FET cycles conducted in four infertility centers were retrospectively collected and reviewed for eligibility from January 2016 and December 2017. Patient's demographics, ovarian stimulation parameters, and pregnancy outcomes were compared between those given GnRH agonist pretreatment versus no pretreatment in ovulatory women undergoing FET cycles. A total of 6397 programmed cycles were screened for eligibility, of which 5049 cycles were included in the study for analysis. Compared with the group of no GnRH agonist pretreatment (n = 4143), women in the GnRH agonist group (n = 906) were older (33.0 vs 34.0, P < .001), had a higher proportion of subjects with previous transfer attempts and had a higher number of embryos transferred. After controlling for confounders, the logistic regression results showed that GnRH agonist pretreatment did not increase the odds of both clinical pregnancy (OR 0.92, 95% CI [0.70-1.20]), ongoing pregnancy (OR 0.91, 95% CI [0.69-1.19]) and live birth rates (OR 0.84, 95% CI [0.64-1.10]). However, when restricted to women who had no previous transfer attempts, women in the GnRH pretreatment group had lower odds of achieving live birth (OR 0.49, 95% CI [0.30-0.79]). Sensitivity analysis performed in patients with male factor infertility causes showed GnRH agonist pretreated group had lower live birth rates compared to no GnRH agonist pretreatment group (OR = 0.65, 95% CI [0.43-0.97]). Our findings suggested that GnRH agonist pretreatment does not bring additional benefits in live birth rate improvements for ovulatory women undergoing FET cycles. Therefore, the pros of using GnRH agonist to reduce premature ovulation should be weighed against the cons of prolonged time to pregnancy, discomforts resulting from pituitary suppression, and increased medical costs associated with GnRH agonist use.

Upregulation of circ_0008812 and circ_0001583 predicts poor prognosis and promotes breast cancer proliferation.

Background: Accumulating evidence suggests that circular RNAs (circRNAs) are highly correlated with tumor progression and pathogenesis in breast cancer. Whereas, their regulatory roles and corresponding mechanisms in breast cancer are still not exhaustive. Thus, we intended to establish circRNA-mediated competive endogenous RNA (ceRNA) network to uncover the possible roles and clinical implications of circRNAs in breast cancer. Methods: Microarray and RNA-sequencing (RNA-seq) data were download from GEO and TCGA database to screen for differentially expressed RNAs (DEcircRNAs, DEmiRNAs, DEmRNAs) in breast cancer. By implementing online databases, we established ceRNA networks, performed gene set enrichment analysis, constructed protein-protein interaction (PPI) networks, and assessed the expression levels and prognostic significance of hub genes. Subsequently, we explored the functions of prognosis-related genes and constructed gene-drug interaction networks. Finally, the functional roles of DEcircRNAs in breast cancer were revealed via MTT and colony formation assay. Results: Based on the identified 8 DEcircRNAs, 25 miRNAs and 216 mRNAs, a ceRNA regulatory network was established. Further analysis revealed that prominent enrichments were transcription factor binding, transforming growth factor-beta (TGF-ß) and Apelin signaling pathway etc. PPI network and survival curves analysis showed that elevated levels of hub genes (RACGAP1 and KPNA2) were associated with poorer prognosis. They were found to be positively relevant to cell cycle and proliferation. Then a prognostic sub-network of ceRNA was constructed, consisting of 2 circRNAs, 4 miRNAs and 2 mRNAs. The gene-drug interaction network showed that numerous drugs could regulate the expression of these two prognosis-related genes. Functional experiments showed that depletion of circ_0008812 and circ_0001583 could significantly inhibit the proliferation of MCF-7 cells. Conclusion: Our study constructed 4 prognostic regulatory axes that are significantly correlated with tumor prognosis in breast cancer patients, and uncover the roles of circ_0008812 and circ_0001583 in breast cancer, providing a new perspective into the molecular mechanisms of breast cancer pathogenesis.

Enhancement of Tendon Repair Using Tendon-Derived Stem Cells in Small Intestinal Submucosa via M2 Macrophage Polarization.

(1) Background: Reconstruction of Achilles tendon defects and prevention of postoperative tendon adhesions were two serious clinical problems. In the treatment of Achilles tendon defects, decellularized matrix materials and mesenchymal stem cells (MSCs) were thought to address both problems. (2) Methods: In vitro, cell adhesion, proliferation, and tenogenic differentiation of tendon-derived stem cells (TDSCs) on small intestinal submucosa (SIS) were evaluated. RAW264.7 was induced by culture medium of TDSCs and TDSCs-SIS scaffold groups. A rat Achilles tendon defect model was used to assess effects on tendon regeneration and antiadhesion in vivo. (3) Results: SIS scaffold facilitated cell adhesion and tenogenic differentiation of TDSCs, while SIS hydrogel coating promoted proliferation of TDSCs. The expression of TGF-ß and ARG-1 in the TDSCs-SIS scaffold group were higher than that in the TDSCs group on day 3 and 7. In vivo, the tendon regeneration and antiadhesion capacity of the implanted TDSCs-SIS scaffold was significantly enhanced. The expression of CD163 was significantly highest in the TDSCs-SIS scaffold group; meanwhile, the expression of CD68 decreased more significantly in the TDSCs-SIS scaffold group than the other two groups. (4) Conclusion: This study showed that biologically prepared SIS scaffolds synergistically promote tendon regeneration with TDSCs and achieve antiadhesion through M2 polarization of macrophages.

Clinical efficacy analysis of oocyte cryopreservation: A propensity score matched study.

OBJECTIVE: To investigate the effectiveness of oocyte thawing cycles in the clinical application of assisted reproductive technology (ART). STUDY DESIGN: The clinical data of 78 cases who underwent oocyte thawing cycles in our center were retrospectively analyzed. All patients in this study received oocyte cryopreservation for the husband reason. According to patient age at egg freezing, patients were divided into three observation groups (Group A, <30 years old; Group B, 30-34 years old; Group C, ≥35 years old), and the control groups were selected by propensity score matching with fresh cycles. The clinical outcomes of each group were compared, and the clinical efficacy of oocyte thawing cycles was analyzed. RESULTS: Clinical pregnancy outcomes of oocyte thawing cycles were not significantly different from that of fresh oocytes, but vitrification affected the number of two pronuclei zygotes developing to cleavage stage and the number of high-quality embryos, and the normal fertilization rate after thawing. The cycle cumulative live birth rate in Group C was significantly lower than those in Groups A and B. The live birth rates per egg of Groups A, B, C were 5.03%, 5.61%, and 3.57%, respectively, and the numbers of eggs per live birth were 13.72, 14.43, and 21.0, respectively. CONCLUSIONS: The overall clinical outcomes of oocyte vitrification were similar to that of fresh oocytes, but the cleavage rate and embryo quality of frozen oocytes were slightly reduced. Freezing of oocytes in women over 35 years of age affects the clinical efficacy of ART.

Folic Acid Preconditioning Alleviated Radiation-Induced Ovarian Dysfunction in Female Mice.

Radiological therapy/examination is the primary source of artificial radiation exposure in humans. While its application has contributed to major advances in disease diagnosis and treatment, ionizing radiation exposure is associated with ovarian damage. The use of natural products, either alone or as an adjunct, has become increasingly common for reducing the side effects of radiological therapy during disease treatment. Herein, we explored the protective effect of folic acid (FA), a widely used B vitamin, against radiation-induced ovarian injury and its mechanism of action. Female mice with normal ovarian function were randomly divided into control, FA, radiation, and radiation + FA groups. The intervention strategy included daily intragastric administration of FA (5 mg/kg) for 3 weeks prior to radiation exposure. Mice in the radiation and radiation + FA groups received a single dose of 5 Gy X-ray irradiation. Changes in the estrous cycle were then recorded, and ovarian tissues were collected. Pathophysiological changes as well as reproductive and endocrine-related indexes were determined via H&E staining, immunohistochemistry, Western blot, and ELISA. The reproductive performance and emotional symptoms of animals were also monitored. Our results indicated that FA intervention effectively alleviated ovarian damage, leading to more regular estrous cycles, lesser impairment of follicular morphology and endocrine status, as well as greater germ cell preservation. Reduced levels of oxidative stress, inflammation, and enhanced DNA repair were associated these changes. FA pre-administration improved the reproductive performance, leading to higher pregnancy rates and greater litter sizes. Further, the anxiety levels of animals were significantly reduced. Our results indicate that FA pre-administration significantly alleviates radiation-induced ovarian damage in rodents, highlighting its potential as a protective strategy against radiation exposure in the female population.

Characterization of Volatile Organic Compounds Produced by Bacillus siamensis YJ15 and Their Antifungal Activity Against Botrytis cinerea.

To develop an effective and environmentally safe strategy to control postharvest gray mold caused by Botrytis cinerea, Bacillus siamensis strain YJ15 isolated from blueberry was used to test the biocontrol potential. It is interesting to find that the volatile organic compounds (VOCs) emitted from strain YJ15 exhibited significant antifungal activity against Botrytis cinerea as well as 11 other plant-pathogenic fungi, with a percentage of mycelial growth inhibition from 74.96 to 92.81%. Additionally, VOCs from strain YJ15 could reduce significantly the disease incidence and lesion diameter with the increasing of fermentation time, indicating great biocontrol potential for controlling blueberry postharvest gray mold. Furthermore, the VOCs were collected by using headspace solid-phase microextraction fiber, and the composition of VOCs was further revealed by using gas chromatography coupled with quadruple mass spectrometry. In total, 24 kinds of VOCs, including 5 alkanes, 2 aldehydes, 3 ketones, 5 alcohols, 1 alkene, 5 acids and esters, 2 aromatic compounds, and 1 sulfur compound, were emitted at 1, 3, 5, and 7 days after inoculation. Among these VOCs, eight antifungal VOCs could inhibit mycelial growth of B. cinerea. It is important to highlight that, although 1-butanol and 3-methyl-1-butanol were the most abundant compounds, 2-ethylhexanol, 1-heptanol, and 1,3-xylene have proved to be more toxic to B. cinerea than 3-methyl-1-butanol, propanethioic acid, 2,2-dimethyl-, ethyl 2-methylbutyrate, 2-heptanone, and 1-butanol, which provide new, promising biofumigants for the control of postharvest gray mold caused by B. cinerea.