Efficacy of electro-acupuncture on pregnancy outcomes for women undergoing in vitro fertilization: study protocol for a pilot randomized controlled trial.

Introduction: In vitro fertilization (IVF) is a technology that assists couples experiencing infertility to conceive children. However, unsuccessful attempts can lead to significant physical and financial strain. Some individuals opt for electro-acupuncture (EA) during IVF, even though there is limited evidence regarding the efficacy of this practice. Thus, this pilot study aims to explore the effectiveness and safety of EA during IVF on pregnancy outcomes. Methods and analysis: This clinical trial is a parallel, randomized, sham-controlled study. It aims to include a total of 118 infertile women who intend to undergo IVF. The participants will be randomly divided into three groups in a 1:1:1 ratio: the EA + IVF group, the placebo electro-acupuncture (pEA) +IVF group, and the IVF control group. All of the patients will be required to use ovarian stimulation drugs, while those in the EA + IVF and pEA + IVF groups will receive acupuncture treatment at three sessions per week (every other day) until trigger day with a minimum five session. The primary outcome of this trial will focus on the clinical pregnancy rate (CPR). CPR is defined as the rate of achieving clinical pregnancy from the first fresh/frozen embryo transfer cycle with an ultrasound-confirmed gestational sac in the uterine cavity. The secondary outcomes will assess embryology data, biochemical pregnancy rate, early miscarriage rate, Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), Pittsburgh Sleep Quality Index (PSQI), Fertile Quality of Life (FertiQoL), patient retention rate, treatment adherence, and safety outcomes. Ethics and dissemination: Ethics approval was obtained from the Ethics Committee of Sichuan Jinxin Xi'nan Women and Children Hospital (number 2021-007). The results will be disseminated through peer-reviewed publications. The participants gave informed consent to participate in the study before taking part in it. Clinical trial registration: https://www.chictr.org.cn, identifier ChiCTR2300074455.

The construction of machine learning-based predictive models for high-quality embryo formation in poor ovarian response patients with progestin-primed ovarian stimulation.

OBJECTIVE: To explore the optimal models for predicting the formation of high-quality embryos in Poor Ovarian Response (POR) Patients with Progestin-Primed Ovarian Stimulation (PPOS) using machine learning algorithms. METHODS: A retrospective analysis was conducted on the clinical data of 4,216 POR cycles who underwent in vitro fertilization (IVF) / intracytoplasmic sperm injection (ICSI) at Sichuan Jinxin Xinan Women and Children's Hospital from January 2015 to December 2021. Based on the presence of high-quality cleavage embryos 72 h post-fertilization, the samples were divided into the high-quality cleavage embryo group (N = 1950) and the non-high-quality cleavage embryo group (N = 2266). Additionally, based on whether high-quality blastocysts were observed following full blastocyst culture, the samples were categorized into the high-quality blastocyst group (N = 124) and the non-high-quality blastocyst group (N = 1800). The factors influencing the formation of high-quality embryos were analyzed using logistic regression. The predictive models based on machine learning methods were constructed and evaluated accordingly. RESULTS: Differential analysis revealed that there are statistically significant differences in 14 factors between high-quality and non-high-quality cleavage embryos. Logistic regression analysis identified 14 factors as influential in forming high-quality cleavage embryos. In models excluding three variables (retrieved oocytes, MII oocytes, and 2PN fertilized oocytes), the XGBoost model performed slightly better (AUC = 0.672, 95% CI = 0.636-0.708). Conversely, in models including these three variables, the Random Forest model exhibited the best performance (AUC = 0.788, 95% CI = 0.759-0.818). In the analysis of high-quality blastocysts, significant differences were found in 17 factors. Logistic regression analysis indicated that 13 factors influence the formation of high-quality blastocysts. Including these variables in the predictive model, the XGBoost model showed the highest performance (AUC = 0.813, 95% CI = 0.741-0.884). CONCLUSION: We developed a predictive model for the formation of high-quality embryos using machine learning methods for patients with POR undergoing treatment with the PPOS protocol. This model can help infertility patients better understand the likelihood of forming high-quality embryos following treatment and help clinicians better understand and predict treatment outcomes, thus facilitating more targeted and effective interventions.

Metabolic landscape and pathogenic insights: a comprehensive analysis of high ovarian response in infertile women undergoing in vitro fertilization.

BACKGROUND: In the realm of assisted reproduction, a subset of infertile patients demonstrates high ovarian response following controlled ovarian stimulation (COS), with approximately 29.7% facing the risk of Ovarian Hyperstimulation Syndrome (OHSS). Management of OHSS risk often necessitates embryo transfer cancellation, leading to delayed prospects of successful pregnancy and significant psychological distress. Regrettably, these patients have received limited research attention, particularly regarding their metabolic profile. In this study, we aim to utilize gas chromatography-mass spectrometry (GC-MS) to reveal these patients' unique serum metabolic profiles and provide insights into the disease's pathogenesis. METHODS: We categorized 145 infertile women into two main groups: the CON infertility group from tubal infertility patients and the Polycystic Ovary Syndrome (PCOS) infertility group. Within these groups, we further subdivided them into four categories: patients with normal ovarian response (CON-NOR group), patients with high ovarian response and at risk for OHSS (CON-HOR group) within the CON group, as well as patients with normal ovarian response (PCOS-NOR group) and patients with high ovarian response and at risk for OHSS (PCOS-HOR group) within the PCOS group. Serum metabolic profiles were analyzed using GC-MS. The risk criteria for OHSS were: the number of developing follicles > 20, peak Estradiol (E2) > 4000pg/mL, and Anti-Müllerian Hormone (AMH) levels > 4.5ng/mL. RESULTS: The serum metabolomics analysis revealed four different metabolites within the CON group and 14 within the PCOS group. Remarkably, 10-pentadecenoic acid emerged as a discernible risk metabolite for the CON-HOR, also found to be a differential metabolite between CON-NOR and PCOS groups. cysteine and 5-methoxytryptamine were also identified as risk metabolites for the PCOS-HOR. Furthermore, KEGG analysis unveiled significant enrichment of the aminoacyl-tRNA biosynthesis pathway among the metabolites differing between PCOS-NOR and PCOS-HOR. CONCLUSION: Our study highlights significant metabolite differences between patients with normal ovarian response and those with high ovarian response and at risk for OHSS within both the tubal infertility control group and PCOS infertility group. Importantly, we observe metabolic similarities between patients with PCOS and those with a high ovarian response but without PCOS, suggesting potential parallels in their underlying causes.

Antimicrobial and hydrophobic cellulose paper prepared by covalently attaching cinnamaldehyde for strawberries preservation.

The demand for paper-based packaging materials as an alternative to incumbent disposable petroleum-derived polymers for food packaging applications is ever-growing. However, typical paper-based formats are not suitable for use in unconventional applications due to inherent limitations (e.g., excessive hydrophilicity, lack antimicrobial ability), and accordingly, enabling new capabilities is necessity. Herein, a simple and environmentally friendly strategy was proposed to introduce antimicrobial and hydrophobic functions to cellulose paper through successive chemical grafting of 3-aminopropyltriethoxysilane (APS) and cinnamaldehyde (CA). The results revealed that cellulose paper not only showed long-term antibacterial effect on different bacteria, but also inhibited a wide range of fungi. Encouragingly, the modified paper, which is fluorine-free, displays a high contact angle of 119.7°. Thus, even in the wet state, the modified paper can still maintain good mechanical strength. Meanwhile, the multifunctional composite papers have excellent biocompatibility and biodegradability. Compared with ordinary cellulose paper, multifunctional composite paper can effectively prolong the shelf life of strawberries. Therefore, the multifunctional composite paper represents good application potential as a fruit packaging material.

Study on the optimal time limit of frozen embryo transfer and the effect of a long-term frozen embryo on pregnancy outcome.

In this retrospective study conducted at Sichuan Jinxin Xinan Women and Children's Hospital spanning January 2015 to December 2021, our objective was to investigate the impact of embryo cryopreservation duration on outcomes in frozen embryo transfer. Participants, totaling 47,006 cycles, were classified into 3 groups based on cryopreservation duration: ≤1 year (Group 1), 1 to 6 years (Group 2), and ≥6 years (Group 3). Employing various statistical analyses, including 1-way ANOVA, Kruskal-Wallis test, chi-square test, and a generalized estimating equation model, we rigorously adjusted for confounding factors. Primary outcomes encompassed clinical pregnancy rate and Live Birth Rate (LBR), while secondary outcomes included biochemical pregnancy rate, multiple pregnancy rate, ectopic pregnancy rate, early and late miscarriage rates, preterm birth rate, neonatal birth weight, weeks at birth, and newborn sex. Patient distribution across cryopreservation duration groups was as follows: Group 1 (40,461 cycles), Group 2 (6337 cycles), and Group 3 (208 cycles). Postcontrolling for confounding factors, Group 1 exhibited a decreased likelihood of achieving biochemical pregnancy rate, clinical pregnancy rate, and LBR (OR < 1, aOR < 1, P < .05). Furthermore, an elevated incidence of ectopic pregnancy was observed (OR > 1, aOR > 1), notably significant after 6 years of freezing time [aOR = 4.141, 95% confidence intervals (1.013-16.921), P = .05]. Cryopreservation exceeding 1 year was associated with an increased risk of early miscarriage and preterm birth (OR > 1, aOR > 1). No statistically significant differences were observed in birth weight or sex between groups. However, male infant birth rates were consistently higher than those of female infants across all groups. In conclusion, favorable pregnancy outcomes align with embryo cryopreservation durations within 1 year, while freezing for more than 1 year may diminish clinical pregnancy and LBRs, concurrently elevating the risk of ectopic pregnancy and preterm birth.

Association of white matter hyperintensities with BMD, incident fractures, and falls in the UK Biobank cohort.

Osteoporosis is the most common metabolic bone disease globally, which increases the healthcare service burden. Recent studies have linked higher white matter hyperintensities (WMH) to reduced BMD, increasing the risk of fractures and falls in older adults. However, limited evidence exists regarding the dose-response relationship between WMH and bone health in a larger and younger population. Our study aimed to examine the association of WMH volume with BMD, incident fractures and falls, focusing on dose-response relationship with varying levels of WMH volume. We included 26 410 participants from the UK Biobank. The association between WMH volume and BMD was analyzed using multiple linear regression. Cox regression models were used to estimate the hazard ratios of incident fractures and falls. Restricted cubic spline (RCS) fitted for linear and Cox regression models were employed to explore potential non-linearity. Over a mean follow-up time of 3.8 yr, we documented 59 hip fractures, 392 all fractures, and 375 fall incidents. When applying RCS, L-shaped relationships were identified between WMH volume and BMD across all 4 sites. Compared with those in the lowest fifth of WMH volume, individuals in the second to the highest fifths were associated with a reduction of 0.0102-0.0305 g/cm2 in femur neck BMD, 0.0075-0.0273 g/cm2 in femur troch BMD, 0.0173-0.0345 g/cm2 in LS BMD, and 0.0141-0.0339 g/cm2 in total body BMD. The association was more pronounced among women and younger participants under age 65 (Pinteraction < .05). Per 1 SD increment of WMH volume was associated with 36.9%, 20.1%, and 14.3% higher risks of incident hip fractures, all fractures, and falls. Genetically determined WMH or apolipoprotein E genotypes did not modify these associations. We demonstrated that a greater WMH was associated with BMD in an L-shaped dose-response manner, especially in women and those under 65 yr.

This study investigated the association between white matter hyperintensities (WMH) and bone health, focusing on BMD, incident fractures and falls. We included 26 410 participants from the UK Biobank and found that a greater WMH volume was associated with BMD in an L-shaped dose­response manner, especially in women and those under 65 yr. Additionally, per 1 SD increment of WMH volume was associated with 36.9%, 20.1%, and 14.3% higher risks of incident hip fractures, all fractures, and falls. These findings emphasize the significance of considering brain health when evaluating bone health.

Age at menarche and risk of ovarian hyperstimulation syndrome in women undergoing IVF/ICSI cycles: a retrospective cohort study.

OBJECTIVES: We aimed to explore the association between age at menarche (AAM) and ovarian hyperstimulation syndrome (OHSS) in fresh in vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) cycles. DESIGN: A retrospective cohort study. SETTING: Data were collected from a large obstetrics and gynaecology hospital in Sichuan, China. PARTICIPANTS: This study included 17 419 eligible women aged ≤40 years who underwent the first IVF/ICSI cycles from January 2015 to December 2021. Women were divided into three groups according to their AAM: ≤12 years (n=5781), 13-14 years (n=9469) and ≥15 years (n=2169). RESULTS: The means of age at recruitment and AAM were 30.4 years and 13.1 years, respectively. Restricted cubic spline models suggested that early menarche age increased the risk of OHSS. The multivariable logistic analysis showed that women with menarche age ≤12 years were more likely to suffer from OHSS (OR 1.321, 95% CI 1.113 to 1.567) compared with those aged 13-14 years among the whole cohort. This significant relationship remained in women administered with different ovarian stimulation protocols and gonadotrophin doses. When stratified by female age, this correlation was presented only in patients aged ≤30 years (OR 1.362, 95% CI 1.094 to 1.694). And the mediation analysis showed that the relationship between AAM and OHSS was totally mediated by antral follicle counts (AFC). CONCLUSION: Menarche age earlier than 12 years may increase the OHSS risk in women aged ≤30 years through the mediation of AFC. More prospective studies are required to verify the results.

Body composition, lifestyle, and depression: a prospective study in the UK biobank.

BACKGROUND: Obesity has been related to depression and adhering healthy lifestyle was beneficial to lower the risk of depression; however, little is known about the relationship between body composition and fat distribution with depression risk and the influence of body composition and fat distribution on the association of lifestyle and depression. Therefore, we aimed to investigate whether body composition and fat distribution were associated with the adverse events of depression and the relationship between lifestyle and depression. METHODS: We included 330,131 participants without depression at baseline in the UK Biobank (mean age, 56.9 years; 53.83% females). The assessment of depression was sourced from health outcomes across self-report, primary care, hospital inpatient data, and death data. Body composition was determined by bioelectrical impedance. Seven lifestyles (no current smoking, moderate alcohol consumption, regular physical activity, healthy diet, less sedentary behavior, healthy sleep pattern, and appropriate social connection) were used to generate a lifestyle score. RESULTS: During a median of 11.7 years of follow-up, 7576 incident depression occurred. All the body composition measures were positively associated with depression risk, with the Hazard ratios (HR) for the uppermost tertile (T3) versus the lowest tertile (T1) ranging from 1.26 (95% CI: 1.15-1.39) for trunk fat-free mass (TFFM) to 1.78 (1.62-1.97) for leg fat percentage (LFP). In addition, we found significant interactions between fat mass-related indices, especially leg fat mass (LFM) (p = 1.65 × 10-9), and lifestyle score on the risk of depression, for which the beneficial associations of a healthy lifestyle with the risk of depression were more evident among participants with low body fat measurement. CONCLUSIONS: High levels of body composition measures were associated with an increased depression risk. Adverse body composition measures may weaken the link between a healthy lifestyle and a reduced risk of depression.

The association of post-embryo transfer SARS-CoV-2 infection with early pregnancy outcomes in in vitro fertilization: a prospective cohort study.

BACKGROUND: The influence of SARS-CoV-2 infection after embryo transfer on early pregnancy outcomes in in vitro fertilization or intracytoplasmic sperm injection-embryo transfer treatment remains inadequately understood. This knowledge gap endures despite an abundance of studies investigating the repercussions of preceding SARS-CoV-2 infection on early pregnancy outcomes in spontaneous pregnancies. OBJECTIVE: This study aimed to investigate the association between SARS-CoV-2 infection within 10 weeks after embryo transfer and early pregnancy outcomes in patients undergoing in vitro fertilization/intracytoplasmic sperm injection treatment. STUDY DESIGN: This prospective cohort study was conducted at a single public in vitro fertilization center in China. Female patients aged 20 to 39 years, with a body mass index ranging from 18 to 30 kg/m2, undergoing in vitro fertilization/intracytoplasmic sperm injection treatment, were enrolled between September 2022 and December 2022, with follow-up extended until March 2023. The study tracked SARS-CoV-2 infection time (≤14 days, ≤28 days, and ≤10 weeks after embryo transfer), symptoms, vaccination status, the interval between vaccination and embryo transfer, and early pregnancy outcomes, encompassing biochemical pregnancy rate, implantation rate, clinical pregnancy rate, and early miscarriage rate. The study used single-factor analysis and multivariate logistic regression to examine the association between SARS-CoV-2 infection status, along with other relevant factors, and the early pregnancy outcomes. RESULTS: A total of 857 female patients undergoing in vitro fertilization/intracytoplasmic sperm injection treatment were analyzed. In the first stage, SARS-CoV-2 infection within 14 days after embryo transfer did not have a significant negative association with the biochemical pregnancy rate (adjusted odds ratio, 0.74; 95% confidence interval, 0.51-1.09). In the second stage, SARS-CoV-2 infection within 28 days after embryo transfer had no significant association with the implantation rate (36.6% in infected vs 44.0% in uninfected group; P=.181). No statistically significant association was found with the clinical pregnancy rate after adjusting for confounding factors (adjusted odds ratio, 0.69; 95% confidence interval, 0.56-1.09). In the third stage, SARS-CoV-2 infection within 10 weeks after embryo transfer had no significant association with the early miscarriage rate (adjusted odds ratio, 0.77; 95% confidence interval, 0.35-1.71). CONCLUSION: Our study suggests that SARS-CoV-2 infection within 10 weeks after embryo transfer may not be negatively associated with the biochemical pregnancy rate, implantation rate, clinical pregnancy rate, and early miscarriage rate in patients undergoing in vitro fertilization/intracytoplasmic sperm injection treatment. It is important to note that these findings are specific to the target population of in vitro fertilization/intracytoplasmic sperm injection patients aged 20 to 39 years, without previous SARS-CoV-2 infection, and with a body mass index of 18 to 30 kg/m2. This information offers valuable insights, addressing current concerns and providing a clearer understanding of the actual risk associated with SARS-CoV-2 infection after embryo transfer.

Variation in VEGFA and risk of cardiovascular disease in the UK Biobank.

Background: Cardiovascular disease (CVD) is an escalating global health crisis, contributing significantly to worldwide mortality and morbidity. Dyslipidemia stands as a critical risk factor for CVD. Vascular endothelial growth factor A (VEGFA) is pivotal in angiogenesis and represents a clinical target for CVD intervention. However, the impact of genetic modulation of VEGFA on lipid levels and the subsequent risk of cardiovascular events remains unclear. Methods: We used LDpred2 to calculate genetic scores for lipid levels based on VEGFA variation, serving as instrumental variables to simulate the effect of VEGFA inhibitors. We then assessed the associations between genetic risk for lipid levels and CVD risk by conducting One-sample Mendelian randomization. Results: Our results indicated that low-density lipoprotein cholesterol [LDL-C; odds ratio (OR) = 1.09, 95% CI: 1.06-1.11], remnant cholesterol (RC; OR = 1.24, 95% CI: 1.13-1.36), and triglycerides (TG; OR = 1.14, 95% CI: 1.07-1.22) were positively associated with the incidence of CVD. In contrast, high-density lipoprotein cholesterol (HDL-C) was inversely associated with the incidence of CVD (OR = 0.80, 95% CI: 0.76-0.86). When considering the genetic score for LDL-C constructed based on VEGFA, the group with a high genetic score demonstrated an elevated CVD risk (OR = 1.11, 95% CI: 1.04-1.19) compared to those with a low genetic score. Notably, One-sample Mendelian randomization results provided evidence of a causal relationship between LDL-C and CVD (p = 8.4×10-3) when using genetic variation in VEGFA as an instrumental variable. Conclusions: Genetic variation mimicking the effect of VEGFA inhibition, which lowers LDL-C levels, was causally associated with a reduced risk of cardiovascular events. These findings offer insight into the potential therapeutic relevance of modulating VEGFA-mediated lipid changes in the prevention and management of CVD.

Young obese patients may benefit from GnRH-a long protocol contributing to higher implantation rate and live birth rate of fresh IVF-ET cycles.

Introduction: Obesity has detrimental influences on women reproductive health. There is little experience in optimizing controlled ovarian hyperstimulation (COH) protocols to treat Chinese obese patients who are undergoing in vitro fertilization and embryo transfer (IVF-ET) therapy. Methods: The clinical outcome differences were retrospectively analyzed among obese patients who received gonadotrophin-releasing hormone agonist (GnRH-a), GnRH antagonist (GnRH-ant), micro dose GnRH-a (mGnRH-a) and GnRH-a long protocol in IVF-ET cycle at Chengdu Jinjiang Hospital for Women's and Children's Health from January 2014 to December 2019. Results: The transplantation rate of the GnRH-a long protocol group (59.1%) was higher than that of the GnRH-ant (25.9%) and mGnRH-a (36.7%) groups. The total live birth rate of the GnRH-a long protocol group (46.2%) was higher than that of the GnRH-a group (25.9%) and GnRH-ant group (40.3%). The total number of frozen embryos in the GnRH-ant group was higher than in the other groups (P < 0.05). After adjusting for confounding factors, the logistic regression analysis showed that the GnRH-a long protocol group had higher probabilities of biochemical pregnancy, clinical pregnancy, and live birth than the GnRH-a protocol group. The Gn dose in the mGnRH-a group was higher than the other three groups. Whether single or twin, there were similar neonatal outcomes among the four groups including premature birth rate, Apgar score, newborn weight, and length. Conclusion: For young obese patients undergoing IVF-ET, the GnRH-a long protocol for COH gives better pregnancy outcomes.

A novel method to identify and characterize personalized functional driver lncRNAs in cancer samples.

Cancer is a highly heterogeneous disease, and different individuals of the same cancer type can display different therapeutic effects and prognosis. Genetic variation of long non-coding RNA is the key factor driving tumor development, and plays an important role in genetic and biological heterogeneity. Therefore, it is of great significance to identify lncRNA as a driving factor in the non-coding region and explain its function in tumors for revealing the pathogenesis of cancer. In this study, we developed an integrated method to identify Personalized Functional Driver lncRNAs (PFD-lncRNAs) by integrating the DNA copy number data, gene expression data, and the biological subpathways information. Then, we applied the method to identify 2695 PFD-lncRNAs in 5334 samples across 19 cancer types. We performed an analysis of the association between PFD-lncRNAs and drug sensitivity, which provides medication guidance in disease therapy and drug discovery in the individual. Our research is of great significance for elucidating the biological roles of lncRNA genetic variation in cancer, revealing the related mechanism of cancer, and providing novel insights for individualized medicine.

Effect of serum progesterone on human chorionic gonadotropin trigger day / metaphase II oocyte ratio on pregnancy and neonatal outcomes in women undergoing ICSI cycle.

BACKGROUND: The serum progesterone on human chorionic gonadotropin trigger day / metaphase II oocyte (P/MII) ratio might be a more predictable indicator of pregnancy and neonatal outcomes as compare to P/estradiol (E2) or P alone. Hence, we conducted a larger population study to compare the pregnancy and neonatal outcomes in the low and high P/MII ratio. METHODS: A retrospective, single-center, larger population cohort study between January 2015 and August 2021. Calculate the threshold effect of P/MII ratio on clinical pregnancy rate according to the construct smooth curve fitting. Divide data into two groups by threshold for comparison. RESULTS: 3566 fresh ICSI-ET cycles were included, in which 929 singleton delivery and 676 twin deliveries. Compare to P/MII ≤ 0.367 group, it indicated that the P/MII > 0.367 group had a lower clinical pregnancy rate and live birth rate, furthermore, a significantly higher rate of LBW and SGA were observed in the singleton and twin deliveries. No deleterious impact of high P/MII ratio on embryo quality and undesirable pregnancy outcomes was shown. CONCLUSIONS: When P/MII is higher than 0.367, may have adverse impacts on pregnancy and neonatal outcomes for ICSI cycle.

Reversal of liver failure using a bioartificial liver device implanted with clinical-grade human-induced hepatocytes.

Liver resection is the first-line treatment for primary liver cancers, providing the potential for a cure. However, concerns about post-hepatectomy liver failure (PHLF), a leading cause of death following extended liver resection, have restricted the population of eligible patients. Here, we engineered a clinical-grade bioartificial liver (BAL) device employing human-induced hepatocytes (hiHeps) manufactured under GMP conditions. In a porcine PHLF model, the hiHep-BAL treatment showed a remarkable survival benefit. On top of the supportive function, hiHep-BAL treatment restored functions, specifically ammonia detoxification, of the remnant liver and facilitated liver regeneration. Notably, an investigator-initiated study in seven patients with extended liver resection demonstrated that hiHep-BAL treatment was well tolerated and associated with improved liver function and liver regeneration, meeting the primary outcome of safety and feasibility. These encouraging results warrant further testing of hiHep-BAL for PHLF, the success of which would broaden the population of patients eligible for liver resection.

USP15 Represses Hepatocellular Carcinoma Progression by Regulation of Pathways of Cell Proliferation and Cell Migration: A System Biology Analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) leads to 600,000 people's deaths every year. The protein ubiquitin carboxyl-terminal hydrolase 15 (USP15) is a ubiquitin-specific protease. The role of USP15 in HCC is still unclear. METHOD: We studied the function of USP15 in HCC from the viewpoint of systems biology and investigated possible implications using experimental methods, such as real-time polymerase chain reaction (qPCR), Western blotting, clustered regularly interspaced short palindromic repeats (CRISPR), and next-generation sequencing (NGS). We investigated tissues samples of 102 patients who underwent liver resection between January 2006 and December 2010 at the Sir Run Run Shaw Hospital (SRRSH). Tissue samples were immunochemically stained; a trained pathologist then scored the tissue by visual inspection, and we compared the survival data of two groups of patients by means of Kaplan-Meier curves. We applied assays for cell migration, cell growth, and wound healing. We studied tumor formation in a mouse model. RESULTS: HCC patients (n = 26) with high expression of USP15 had a higher survival rate than patients (n = 76) with low expression. We confirmed a suppressive role of USP15 in HCC using in vitro and in vivo tests. Based on publicly available data, we constructed a PPI network in which 143 genes were related to USP15 (HCC genes). We combined the 143 HCC genes with results of an experimental investigation to identify 225 pathways that may be related simultaneously to USP15 and HCC (tumor pathways). We found the 225 pathways enriched in the functional groups of cell proliferation and cell migration. The 225 pathways determined six clusters of pathways in which terms such as signal transduction, cell cycle, gene expression, and DNA repair related the expression of USP15 to tumorigenesis. CONCLUSION: USP15 may suppress tumorigenesis of HCC by regulating pathway clusters of signal transduction for gene expression, cell cycle, and DNA repair. For the first time, the tumorigenesis of HCC is studied from the viewpoint of the pathway cluster.

Isoalantolactone suppresses gallbladder cancer progression via inhibiting the ERK signalling pathway.

CONTEXT: Gallbladder cancer (GBC) is the most common malignant tumour of the biliary tract. Isoalantolactone (IAL), an active sesquiterpene lactone compound isolated from the roots of Inula helenium L. (Asteraceae), has antitumour effects. OBJECTIVE: This study investigates the effects of IAL on GBC. MATERIALS AND METHODS: In vitro, NOZ and GBC-SD cells were treated with IAL (0, 10, 20 and 40 µM) for 24 h. The DMSO-treated cells were selected as a control. Cell proliferation, migration, invasion and apoptosis were measured by the CCK-8 assay, transwell assay, flow cytometry and western blot. In vivo, subcutaneous tumour xenografts were constructed by injecting nude mice (BALB/C) with 5 × 106 NOZ cells. Mice were divided into the control group (equal amount of DMSO), the IAL group (10 mg/kg/day) and the IAL + Ro 67-7476 group (IAL, 10 mg/kg/day; Ro 67-7476, 4 mg/kg/day). The study duration was 30 days. RESULTS: Compared with the DMSO group, cell proliferation of NOZ (IC50 15.98 µM) and GBC-SD (IC50 20.22 µM) was inhibited by about 70% in the IAL 40 µM group. Migration and invasion were suppressed by about 80%. Cell apoptosis rate was increased about three-fold. The phosphorylation level of ERK was decreased to 30-35%. Tumour volume and weight (about 80% reduction) were suppressed by IAL in vivo. Moreover, the effects of IAL were abolished by Ro 67-7476 in vitro and in vivo. DISCUSSION AND CONCLUSIONS: Our findings indicate that IAL could inhibit GBC progression in vitro and in vivo by inhibiting the ERK signalling pathway.

Low LH level does not indicate poor IVF cycle outcomes with GnRh-a single trigger: a retrospective analysis.

OBJECTIVE: To compare the in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycle outcomes between patients with low and normal serum luteinizing hormone (LH) levels on the day after a gonadotropin-releasing hormone agonist (GnRH-a) single trigger. We further investigated the efficacy of human chorionic gonadotropin (hCG) retrigger on IVF cycle outcomes in patients with low LH levels after GnRH-a single trigger. METHODS: We retrospectively analyzed 957 infertile patients (tubal factor, ovulation disorders, male sperm factor, or unexplained infertility) who were treated with IVF/ICSI at the Chengdu Xinan Gynecology Hospital from July 2017 to December 2020. Patients received sufficient GnRH-a single trigger were divided into two groups based on the serum LH levels on the next day of trigger: normal serum LH levels (≥ 10 mIU/mL) group (control group, n = 906) and low LH levels (< 10 mIU/mL) group (experimental group, n = 51). And the efficacy of hCG retrigger on IVF/ICSI cycle outcomes in 10 patients with low LH levels after GnRH-a single trigger. RESULTS: There were no significant differences in IVF/ICSI cycle outcomes, including egg yield, two pronuclei fertilization rate, excellent embryo rate, or live birth rate of frozen-thawed embryos between patients with low and normal LH levels after GnRH-a trigger. It showed significantly higher risk of ovarian hyperstimulation syndrome in the group of low LH levels [ 0.7%(1/137) vs. 8.5%(4/47), P = 0.016] compared with the group of normal LH levels who received GnRH-a single trigger. The hCG retrigger had no obvious efficacy on cycle outcomes in patients with low LH levels, including oocytes retrieved, fertilization rate, embryo conditions, and live birth rate of frozen-thawed cycles. CONCLUSION: The IVF/ICSI cycle outcomes of patients with low LH levels on the day after GnRH-a administration were similar to those of patients with normal LH levels. Blood LH test might not be required on the day following the trigger. The hCG retrigger did not have any effect on the cycle outcomes, suggesting that immediate retriggering with hCG was unnecessary.

Nomogram models to predict low fertilisation rate and total fertilisation failure in patients undergoing conventional IVF cycles.

OBJECTIVES: To establish visualised prediction models of low fertilisation rate (LFR) and total fertilisation failure (TFF) for patients in conventional in vitro fertilisation (IVF) cycles. DESIGN: A retrospective cohort study. SETTING: Data from August 2017 to August 2021 were collected from the electronic records of a large obstetrics and gynaecology hospital in Sichuan, China. PARTICIPANTS: A total of 11 598 eligible patients who underwent the first IVF cycles were included. All patients were randomly divided into the training group (n=8129) and the validation group (n=3469) in a 7:3 ratio. PRIMARY OUTCOME MEASURE: The incidence of LFR and TFF. RESULTS: Logistic regressions showed that ovarian stimulation protocol, primary infertility and initial progressive sperm motility were the independent predictors of LFR, while serum luteinising hormone and P levels before human chorionic gonadotropin injection and number of oocytes retrieved were the critical predictors of TFF. And these indicators were incorporated into the nomogram models. According to the area under the curve values, the predictive ability for LFR and TFF were 0.640 and 0.899 in the training set and 0.661 and 0.876 in the validation set, respectively. The calibration curves also showed good concordance between the actual and predicted probabilities both in the training and validation group. CONCLUSION: The novel nomogram models provided effective methods for clinicians to predict LFR and TFF in traditional IVF cycles.

An Individualized Recommendation for Controlled Ovary Stimulation Protocol in Women Who Received the GnRH Agonist Long-Acting Protocol or the GnRH Antagonist Protocol: A Retrospective Cohort Study.

Background: The GnRH agonist long-acting protocol and GnRH antagonist protocol are widely used in ovarian stimulation. Which protocol eliciting higher live birth rate for IVF/ICSI patients with different ages, different ovarian reserves and different body mass index (BMI) has not been studied. However, among these protocols, the one that elicits higher live birth in IVF/ICSI patients with different ages, ovarian reserves and body mass indexes (BMI) has not been identified. Methods: This was a retrospective cohort study about 8579 women who underwent the first IVF-ET from January, 2018 to August, 2021. Propensity Score Matching (PSM) was used to improve the comparability between two protocols. Results: After PSM, significant higher live birth rates were found in the GnRH agonist long-acting protocol compared to GnRH antagonist protocol (44.04% vs. 38.32%) (p<0.001). Stratified analysis showed that for those with AMH levels between 3 ng/ml and 6 ng/ml, with BMI ≥ 24 kg/m2 and were aged ≥ 30 years old, and for those women with BMI < 24kg/m2 and were aged ≥30 years whose AMH levels were ≤ 3ng/ml, the GnRH agonist long-acting protocol was more likely to elicit live births [OR (95%CI), 2.13(1.19,3.80)], [OR (95%CI), 1.41(1.05,1.91)]. However, among women with BMI ≥ 24kg/m2 and were aged ≥30 years whose AMH levels were ≤ 3ng/ml, the GnRH agonist long-acting protocol had a lower possibility of eliciting live births [OR (95%CI), 0.54(0.32,0.90)]. Also, among women with AMH levels between 3 ng/ml and 6 ng/ml, with BMI ≥ 24 kg/m2 and with age < 30 years and for those with AMH levels between 3 ng/ml and 6 ng/ml, regardless of age, and with BMI<24kg/m2,, the possibility of live births was similar between the two protocols [OR (95%CI), 1.06(0.60,1.89)], [OR (95%CI), 1.38(0.97,1.97)], [OR (95%CI), 0.99(0.72,1.37)]. Among the women with AMH levels ≤ 3 ng/ml and with were aged < 30years, regardless of BMI, the possibility of live birth was similar between the two protocols [OR (95%CI), 1.02(0.68,1.54)], [OR (95%CI), 1.43(0.68,2.98)]. Moreover, among women with AMH levels ≥ 6ng/ml, the possibility of live birth was similar between the two protocols [OR (95%CI),1.42(0.75,2.69)], [OR (95%CI),1.02(0.19,5.35)], [OR (95%CI), 1.68(0.81,3.51)], [OR (95%CI), 0.51(0.10,2.55)]. Conclusions: The suitability of the GnRH agonist long-acting protocol or GnRH antagonist protocol to infertility patients is dependent on specific biological characteristics of the patients.