Retinoic acid related orphan receptor α is a genetic modifier that rescues retinal degeneration in a mouse model of Stargardt disease and Dry AMD.

Degeneration of the macula is associated with several overlapping diseases including age-related macular degeneration (AMD) and Stargardt Disease (STGD). Mutations in ATP Binding Cassette Subfamily A Member 4 (ABCA4) are associated with late-onset dry AMD and early-onset STGD. Additionally, both forms of macular degeneration exhibit deposition of subretinal material and photoreceptor degeneration. Retinoic acid related orphan receptor α (RORA) regulates the AMD inflammation pathway that includes ABCA4, CD59, C3 and C5. In this translational study, we examined the efficacy of RORA at attenuating retinal degeneration and improving the inflammatory response in Abca4 knockout (Abca4-/-) mice. AAV5-hRORA-treated mice showed reduced deposits, restored CD59 expression and attenuated amyloid precursor protein (APP) expression compared with untreated eyes. This molecular rescue correlated with statistically significant improvement in photoreceptor function. This is the first study evaluating the impact of RORA modifier gene therapy on rescuing retinal degeneration. Our studies demonstrate efficacy of RORA in improving STGD and dry AMD-like disease.

Bromocriptine sensitivity in bromocriptine-induced drug-resistant prolactinomas is restored by inhibiting FGF19/FGFR4/PRL.

PURPOSE: At present, various treatment strategies are available for pituitary adenomas, including medications, surgery and radiation. The guidelines indicate that pharmacological treatments, such as bromocriptine (BRC) and cabergoline (CAB), are important treatments for prolactinomas, but drug resistance is an urgent problem that needs to be addressed. Therefore, exploring the mechanism of drug resistance in prolactinomas is beneficial for clinical treatment. METHODS: In our research, BRC-induced drug-resistant cells were established. Previous RNA sequencing data and an online database were used for preliminary screening of resistance-related genes. Cell survival was determined by Cell Counting Kit-8 (CCK-8) assay, colony formation assays and flow cytometry. Quantitative real-time polymerase chain reaction (qRT‒PCR), western blotting, immunohistochemistry, immunofluorescence and Co-immunoprecipitation (Co-IP) were used to assess the molecular changes and regulation. The therapeutic efficacy of BRC and FGFR4 inhibitor fisogatinib (FISO) combination was evaluated in drug-resistant cells and xenograft tumors in nude mice. RESULTS: Consistent with the preliminary results of RNA sequencing and database screening, fibroblast growth factor 19 (FGF19) expression was elevated in drug-resistant cells and tumor samples. With FGF19 silencing, drug-resistant cells exhibited increased sensitivity to BRC and decreased intracellular phosphorylated fibroblast growth factor receptor 4 (FGFR4) levels. After confirming that FGF19 binds to FGFR4 in prolactinoma cells, we found that FGF19/FGFR4 regulated prolactin (PRL) synthesis through the ERK1/2 and JNK signaling pathways. Regarding the effect of targeting FGF19/FGFR4 on BRC efficacy, FISO and BRC synergistically inhibited the growth of tumor cells, promoted apoptosis and reduced PRL levels. CONCLUSION: Overall, our study revealed FGF19/FGFR4 as a new mechanism involved in the drug resistance of prolactinomas, and combination therapy targeting the pathway could be helpful for the treatment of BRC-induced drug-resistant prolactinomas.

[Prone positioning ventilation therapy in acute respiratory distress syndrome: knowns and unknowns in clinical efficacy].

Prone positioning ventilation (PPV) is considered one of the essential therapeutic approaches in the management of acute respiratory distress syndrome (ARDS). Several randomized controlled clinical trials have demonstrated the efficacy of PPV in the treatment of patients with ARDS. However, it is not clear whether PPV treatment can reduce mortality in patients with veno-venous extracorporeal membrane oxygenation (VV-ECMO)-supported ARDS and corona virus disease 2019 (COVID-19)-associated ARDS. This review aims to discuss the known and unknown aspects of the mechanism of PPV for ARDS, the clinical efficacy of PPV for ARDS, VV-ECMO-supported ARDS, and COVID-19-related ARDS.

[Pathogenetic analysis of transfusion-related acute lung injury caused by human leukocytes antigen antibody against human leukocyte antigen].

From September 2019 to October 2020, pathogenetic analysis of three patients clinically diagnosed as transfusion-related acute lung injury (TRALI) caused by human leukocyte antibodies was conducted by Guangzhou Blood Centre, including 2 males and 1 female, aged 56, 50 and 20 years old, respectively. Solid phase agglutination, anti-human globulin test and flow cytometry method were used to detect the presence of antibodies against patients. Sequencing-based human leukocyte antigen (HLA-SBT) typing technique was used to detect the human leukocyte antigen (HLA) genotypes of patients. Lifecodes single antigen class Ⅰ/Ⅱ kit (LSA-Ⅰ/Ⅱ) were used to detect the specificity of HLA-class Ⅰ and class Ⅱ antibodies in donor blood by Luminex 200 liquid suspension chip system. The HLA specific antibodies and corresponding epitopes in donors were also analyzed. The results showed that　HLA class Ⅰ or class Ⅱ specific antibodies against TRALI patients were detected in the blood donors. The plasma of donor 3 received by patient 1 contained antibodies against the patient's HLA-DRB1*09∶01 antigen, and the epitopes mediating the antibody reaction of the donor and recipient were 70R, 31I, 70QA. There were antibodies against the HLA-A*11∶02, HLA-A*11∶01, DRB1*12∶02, and DRB1*09∶01 antigens of patient 2 in the plasma of donor 4, and the associated antigenic epitopes were 151AHA, 57V, and 16Y. Antibodies against the HLA-DRB1*14∶04, DRB1*11∶01, and DPB1*05∶01 antigens of patient 3 were present in the plasma of donor 6 and donor 7, and the associated epitopes were 96HK, 140TV, 13SE, and 111K.　Three cases of TRALI were confirmed to be caused by HLA antibodies through laboratory analysis, and human leukocyte antibody detection should be paid attention in clinically suspected cases of TRALI, and targeted diagnosis and treatment should be given.

[Evaluation of the efficacy of medial open wedge high tibial osteotomy combined with anterior cruciate ligament reconstruction in the treatment of varus knee osteoarthritis with anterior cruciate ligament injury].

Objective: To evaluate the efficacy of medial open wedge high tibial osteotomy (MOWHTO) combined with anterior cruciate ligament (ACL) reconstruction in the treatment of varus knee osteoarthritis (OA) with ACL injury. Methods: A follow-up study. The study retrospectively analyzed the patients underwent MOWHTO combined with ACL reconstruction for treatment of varus knee OA with ACL injury in Tianjin Hospital between April 2018 and September 2022. The preoperative and postoperative posterior slope angle (PSA), hip-knee-ankle angle (HKA), visual analog scale (VAS) pain scores, Lysholm score, International Knee Documentation Committee (IKDC) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and Tegner score were compared. The follow-up indicators were recorded at 6 weeks, 3 months and 1 year after operation, and the complications were recorded. Results: The study included 32 patients (23 males, 9 females) with a mean age of (50.7±8.4) years. The mean follow-up time was (21.2±4.8) months. PSA increased from 9.2°±1.8° preoperatively to 11.1°±2.4° postoperatively, and HKA increased from 168.7°±2.2° to 181.5°±2.2° (both P<0.01). The indicators such as VAS score (6.8±1.1 vs 1.8±0.4), Lysholm score (52.6±7.1 vs 82.0±6.4), IKDC score (64.7±6.2 vs 80.3±10.0), WOMAC score (51.8±6.3 vs 81.8±6.5), and Tegner score (1.9±0.6 vs 5.0±1.0) were all improved after the operation (all P<0.01). Complications occurred in 5 patients (15.6%), including hematomas, sensory abnormalities, intermuscular vein thrombosis and correction angle loss. Conclusion: MOWHTO combined with ACL reconstruction is a safe and effective approach for the treatment of varus knee OA with ACL injury.

[Changes of hemodynamic parameters in normal pregnant women and their relationship with maternal basic characteristics].

Objective: To investigate the variation of reference ranges of hemodynamic parameters in normal pregnancy and their relation to maternal basic characteristics. Methods: A total of 598 healthy pregnant women who underwent regular prenatal examination at the Third Affiliated Hospital of Guangzhou Medical University from January to December 2023 were prospectively enrolled, and noninvasive hemodynamic monitors were used to detect changes in hemodynamic parameters of the pregnant women with the week of gestation, including cardiac output (CO), stroke volume (SV), thoracic fluid content (TFC), systemic vascular resistance (SVR), mean arterial pressure (MAP), and heart rate (HR). Relationships between hemodynamic parameters and maternal basic characteristics, including age, height, and weight, were analyzed using restricted cubic spline. Results: (1) CO (r=0.155, P<0.001), TFC (r=0.338, P<0.001), MAP (r=0.204, P<0.001), and HR (r=0.352, P<0.001) were positively correlated with the week of gestation, and SV was negatively correlated with the week of gestation (r=-0.158, P<0.001). There was no significant correlation between SVR and gestational age (r=-0.051, P=0.258). (2) CO exhibited a positive correlation with maternal height and weight (all P<0.001). The taller and heavier of pregnant women, the higher their CO. A linear relationship was observed between maternal weight and SV, MAP and HR (all P<0.01). As maternal weight increased, SV, MAP and HR showed an upward trend. Furthermore, there was an inverse association between maternal age and SVR (P<0.001). (3) There was a significant nonlinear association observed between TFC and body mass index during pregnancy (P<0.05). Additionally, a nonlinear relationship was found between SVR and MAP in relation to maternal age (all P<0.05). Notably, when the age exceeded 31 years old, there was an evident upward trend observed in both SVR and MAP. Conclusions: The hemodynamic parameters of normal pregnant women are influenced by their height, body weight, and age. It is advisable to maintain a reasonable weight during pregnancy and give birth at an appropriate age.

[Epidemic characteristics of mycoplasma pneumoniae infection and drug-resistant gene mutations in hospitalized children aged 0-17 in Ningbo City from 2019 to 2023].

To analyze the infection and drug-resistant gene 23S rRNA mutations of mycoplasma pneumoniae (Mp) in hospitalized children aged 0-17 in Ningbo City from 2019 to 2023. Throat swabs were collected from hospitalized children with respiratory tract infections in Ningbo University Affiliated Women and Children's Hospital from 2019 to 2023. They were subjected to real-time fluorescence quantitative polymerase chain reaction detection to analyze Mp infection and drug-resistant gene (23S rRNA) mutations. Intergroup comparisons were made by the Chi-square test or Fisher's exact probability method. A total of 18 968 hospitalized children were included, with a total positive rate of 30.37% (5 760/18 968). The total positive rate of drug-resistant gene mutations was 82.45% (4 749/5 760). The positive rate of Mp in male children was 29.26%, which was lower than that in female children (31.67%, χ2=12.948, P<0.001). The positive rate of Mp drug-resistant gene mutations in male children was 82.52%, which was higher than that in female children(82.37%, χ2=0.021, P=0.885). The positive rates of Mp increased with age (χ2=1 722.21, P<0.001). The positive rates of Mp drug-resistant gene mutations also increased with age (χ2=13.152, P<0.001). In the four seasons, the total positive rate of Mp in summer and autumn was significantly higher than that in winter and spring (χ2=1 085.149, P<0.001). Among them, the Mp positive rates in the summer and autumn of 2019 were as high as 38.26% and 34.49%, while in the summer and autumn of 2020, the Mp positive rates were 2.55% and 1.65%, respectively, which were the lowest in previous years. In the summer and autumn of 2023, the Mp positive rates increased to 47.22% and 51.06%. There was no statistically significant difference in the detection rate of Mp drug-resistant gene mutations among the four seasons. In Conclusion, Mp infection was more prevalent in the summer and autumn in Ningbo city and females and children aged 7-17 were more susceptible. The epidemic of Mp infection in Ningbo occurred in the summer of 2019. After the COVID-19 pandemic in 2020, the positive rate of Mp rapidly decreased and later remained in a low incidence state. After the lifting of restrictive prevention and control measures in 2023, the Mp positive rate returned to an epidemic state. The positive rate of Mp drug-resistant gene (23S rRNA) mutations was relatively high.

[Research progress of long-chain non-coding RNA in lipid metabolism reprogramming in primary hepatocellular carcinoma].

Hepatocellular carcinoma (HCC) is the most common liver malignant tumor with complex pathogenesis and a poor prognosis. Metabolic reprogramming has been recognized as one of the important cancer markers, and the liver, as an important organ for lipid metabolism in the human body, plays an important role in the process of the occurrence and development of HCC. More and more evidence shows that long-chain non-coding RNA (lncRNA) can influence the lipid metabolism process by regulating key enzymes and transcription factors, as well as being involved in the occurrence and development of HCC. Therefore, explicating the mechanism of lncRNA in lipid metabolism reprogramming is conducive to providing new targets and strategies for the diagnosis and treatment and improving the prognosis of HCC patients. This article summarizes the latest research progress on the involvement of lncRNA in the reprogramming process of HCC lipid metabolism.

[Research progress of non-coding RNA-encoding polypeptides in primary hepatocellular carcinoma].

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, with rapid progression and a poor prognosis. More and more studies have shown that there are small open reading frames (sORFs) on the molecular sequences of a large number of non-coding RNAs (ncRNAs), which can encode conserved peptides that play an important role in controlling the occurrence and development of HCC. This article introduces the discovery, prediction, and validation methods of ncRNA-encoding polypeptides and reviews its research progress, with the aim of providing new targets and ideas for early-stage diagnosis, targeted therapy, and prognosis assessment of HCC.

[The effectiveness and safety of the anti gastroesophageal reflux system in the treatment of gastroesophageal reflux disease: a single center study of 23 cases].

Objective: To evaluate the safety and efficacy of domestically produced magnetic sphincter augmentation (MSA) for gastroesophageal reflux disease. Method: This study is a prospective cohort study. Patients with typical heartburn and reflux symptoms (at least partial response to proton pump inhibitors), abnormal esophageal acid exposure and normal esophageal peristalsis were included, prospectively in the Department of Gastroesophageal Surgery, Rocket Force Characteristic Medical Center from June 2019 to September 2022. Patients with hiatal hernia >2 cm and severe esophagitis were excluded. The MSA was wrapped around the distal esophagus after esophageal hiatus repair by laparoscopy. A postoperative questionnaire survey was conducted to assess the relief of symptom, complications, the discontinuation rate of proton pump inhibitor, and surgical satisfaction. Gastroscopy, high-resolution esophageal pressure measurement, and pH value impedance monitoring were also reviewed. Result: Currently, 23 patients with gastroesophageal reflux disease were enrolled and underwent MSA surgery. There were 20 males and 3 females, aged (M (IQR)) 48 (14) years (range: 25 to 64 years). All cases were successfully implanted with MSA. Subjective indicators were followed for 17 (18) months (range: 14 to 53 months), while objective indicators were followed for 17 (1) months (range: 12 to 23 months). The postoperative gastrointestinal and extraesophageal symptom scores showed a significant decrease compared to preoperative levels as follows: the degree of subjective relief of overall digestive symptoms was 90 (20)% (range:0~100%), the degree of subjective relief of overall respiratory symptoms was 100(10)% (range: 10%~100%), the overall satisfaction rate was 83% (19/23), the proton pump inhibitor discontinuation rate was 70% (16/23). The proportion of esophagitis has decreased from 44% (10/23) to 9% (2/23) (κ=0.169, P=0.039), The Hill grade of gastroesophageal valve morphology improved from 1 case of grade Ⅰ, 5 cases of grade Ⅱ, 10 cases of grade Ⅲ, and 7 cases of grade Ⅲ preoperative to 22, 1, 0, and 0 cases postoperative. The proportion of lower esophageal sphincter pressure below normal has decreased from 70% (16/23) to 35% (8/23) (κ=0.170, P=0.012). There were 21 patients who restored normal esophageal acid exposure. Eleven patients had mild long-term dysphagia, but it didn't affect their daily life. No postoperative device migration, erosion, or secondary surgical removal occurred. Conclusions: Laparoscopic implantation of the MSA device was safe and well tolerated. It can effectively control the symptoms of gastroesophageal reflux disease, reduce medication, restore normal cardia morphology and function, and esophageal acid exposure. The main postoperative complication was dysphagia, but it was relatively mild.

[Peripheral sterile corneal infiltrates after small incision lenticule extraction].

A 31-year-old female patient with refractive error in both eyes underwent small incision lenticule extraction. On the 4th day after surgery, arc-shaped peripheral corneal infiltrates appeared in the right eye. Tobramycin and dexamethasone eye drops, 0.3% gatifloxacin eye drops, and a corneal bandage lens were applied to the eye. After bacterial infection was ruled out, dexamethasone sodium phosphate was injected subconjunctivally near the corneal lesion. The symptoms improved and the corneal lesion subsided afterwards.

Measurements of the Elliptic and Triangular Azimuthal Anisotropies in Central

The elliptic (v_{2}) and triangular (v_{3}) azimuthal anisotropy coefficients in central ^{3}He+Au, d+Au, and p+Au collisions at sqrt[s_{NN}]=200 GeV are measured as a function of transverse momentum (p_{T}) at midrapidity (|η|<0.9), via the azimuthal angular correlation between two particles both at |η|<0.9. While the v_{2}(p_{T}) values depend on the colliding systems, the v_{3}(p_{T}) values are system independent within the uncertainties, suggesting an influence on eccentricity from subnucleonic fluctuations in these small-sized systems. These results also provide stringent constraints for the hydrodynamic modeling of these systems.

Erratum: Global Polarization of Ξ and Ω Hyperons in Au+Au Collisions at sqrt[s_{NN}]=200 GeV [Phys. Rev. Lett. 126, 162301 (2021)].

This corrects the article DOI: 10.1103/PhysRevLett.126.162301.

Observation of Directed Flow of Hypernuclei _{Λ}

We report here the first observation of directed flow (v_{1}) of the hypernuclei _{Λ}^{3}H and _{Λ}^{4}H in mid-central Au+Au collisions at sqrt[s_{NN}]=3 GeV at RHIC. These data are taken as part of the beam energy scan program carried out by the STAR experiment. From 165×10^{6} events in 5%-40% centrality, about 8400 _{Λ}^{3}H and 5200 _{Λ}^{4}H candidates are reconstructed through two- and three-body decay channels. We observe that these hypernuclei exhibit significant directed flow. Comparing to that of light nuclei, it is found that the midrapidity v_{1} slopes of _{Λ}^{3}H and _{Λ}^{4}H follow baryon number scaling, implying that the coalescence is the dominant mechanism for these hypernuclei production in the 3 GeV Au+Au collisions.

Measurement of Sequential ϒ Suppression in Au+Au Collisions at sqrt[s_{NN}]=200 GeV with the STAR Experiment.

We report on measurements of sequential ϒ suppression in Au+Au collisions at sqrt[s_{NN}]=200 GeV with the STAR detector at the Relativistic Heavy Ion Collider (RHIC) through both the dielectron and dimuon decay channels. In the 0%-60% centrality class, the nuclear modification factors (R_{AA}), which quantify the level of yield suppression in heavy-ion collisions compared to p+p collisions, for ϒ(1S) and ϒ(2S) are 0.40±0.03(stat)±0.03(sys)±0.09(norm) and 0.26±0.08(stat)±0.02(sys)±0.06(norm), respectively, while the upper limit of the ϒ(3S) R_{AA} is 0.17 at a 95% confidence level. This provides experimental evidence that the ϒ(3S) is significantly more suppressed than the ϒ(1S) at RHIC. The level of suppression for ϒ(1S) is comparable to that observed at the much higher collision energy at the Large Hadron Collider. These results point to the creation of a medium at RHIC whose temperature is sufficiently high to strongly suppress excited ϒ states.

Beam Energy Dependence of Fifth- and Sixth-Order Net-Proton Number Fluctuations in Au+Au Collisions at RHIC.

We report the beam energy and collision centrality dependence of fifth and sixth order cumulants (C_{5}, C_{6}) and factorial cumulants (κ_{5}, κ_{6}) of net-proton and proton number distributions, from center-of-mass energy (sqrt[s_{NN}]) 3 GeV to 200 GeV Au+Au collisions at RHIC. Cumulant ratios of net-proton (taken as proxy for net-baryon) distributions generally follow the hierarchy expected from QCD thermodynamics, except for the case of collisions at 3 GeV. The measured values of C_{6}/C_{2} for 0%-40% centrality collisions show progressively negative trend with decreasing energy, while it is positive for the lowest energy studied. These observed negative signs are consistent with QCD calculations (for baryon chemical potential, µ_{B}≤110 MeV) which contains the crossover transition range. In addition, for energies above 7.7 GeV, the measured proton κ_{n}, within uncertainties, does not support the two-component (Poisson+binomial) shape of proton number distributions that would be expected from a first-order phase transition. Taken in combination, the hyperorder proton number fluctuations suggest that the structure of QCD matter at high baryon density, µ_{B}∼750 MeV at sqrt[s_{NN}]=3 GeV is starkly different from those at vanishing µ_{B}∼24 MeV at sqrt[s_{NN}]=200 GeV and higher collision energies.

Hyperon Polarization along the Beam Direction Relative to the Second and Third Harmonic Event Planes in Isobar Collisions at sqrt[s_{NN}]=200 GeV.

The polarization of Λ and Λ[over ¯] hyperons along the beam direction has been measured relative to the second and third harmonic event planes in isobar Ru+Ru and Zr+Zr collisions at sqrt[s_{NN}]=200 GeV. This is the first experimental evidence of the hyperon polarization by the triangular flow originating from the initial density fluctuations. The amplitudes of the sine modulation for the second and third harmonic results are comparable in magnitude, increase from central to peripheral collisions, and show a mild p_{T} dependence. The azimuthal angle dependence of the polarization follows the vorticity pattern expected due to elliptic and triangular anisotropic flow, and qualitatively disagrees with most hydrodynamic model calculations based on thermal vorticity and shear induced contributions. The model results based on one of existing implementations of the shear contribution lead to a correct azimuthal angle dependence, but predict centrality and p_{T} dependence that still disagree with experimental measurements. Thus, our results provide stringent constraints on the thermal vorticity and shear-induced contributions to hyperon polarization. Comparison to previous measurements at RHIC and the LHC for the second-order harmonic results shows little dependence on the collision system size and collision energy.

Beam Energy Dependence of Triton Production and Yield Ratio (N_{t}×N_{p}/N_{d}

We report the triton (t) production in midrapidity (|y|<0.5) Au+Au collisions at sqrt[s_{NN}]=7.7-200 GeV measured by the STAR experiment from the first phase of the beam energy scan at the Relativistic Heavy Ion Collider. The nuclear compound yield ratio (N_{t}×N_{p}/N_{d}^{2}), which is predicted to be sensitive to the fluctuation of local neutron density, is observed to decrease monotonically with increasing charged-particle multiplicity (dN_{ch}/dη) and follows a scaling behavior. The dN_{ch}/dη dependence of the yield ratio is compared to calculations from coalescence and thermal models. Enhancements in the yield ratios relative to the coalescence baseline are observed in the 0%-10% most central collisions at 19.6 and 27 GeV, with a significance of 2.3σ and 3.4σ, respectively, giving a combined significance of 4.1σ. The enhancements are not observed in peripheral collisions or model calculations without critical fluctuation, and decreases with a smaller p_{T} acceptance. The physics implications of these results on the QCD phase structure and the production mechanism of light nuclei in heavy-ion collisions are discussed.

Uniaxial cyclic stretch enhances osteogenic differentiation of OPLL-derived primary cells via YAP-Wnt/ß-catenin axis.

The pathogenesis of posterior longitudinal ligament ossification (OPLL) remains inadequately understood. Mechanical stimulation is one of the important pathogenic factors in OPLL. As one of the mechanical stimulation transduction signals, the yes-associated protein (YAP) interacts with the Wnt/ß-catenin signalling pathway, which plays an important role in osteogenic differentiation. This study aimed to demonstrate the role of YAP-Wnt/ß-catenin axis in cell differentiation induced by mechanical stress. Primary cells extracted from posterior longitudinal ligament tissues from OPLL or non-OPLL patients were subjected to sinusoidal uniaxial cyclic stretch (5 %, 0.5 Hz, 3 d). The expression of runt-related transcription factor 2, collagen I, osterix, osteocalcin and alkaline phosphatase were compared between the static and the experimental groups. In addition, the cytoskeleton was detected using phalloidin staining while YAP phosphorylation states and nuclear location were identified using immunofluorescence. The results showed that mechanical stretching loading increased the expression of osteogenic genes and proteins in the OPLL group, while it had no significant effect on the control group. When OPLL cells were stretched, YAP exhibited an obvious nuclear translocation and the Wnt/ß-catenin pathway was activated. Knocking down YAP or ß-catenin could weaken the impact upon osteogenic differentiation induced by mechanical stimulation. YAP-mediated mechanical stimulation promoted osteogenic differentiation of OPLL cells through Wnt/ß-catenin pathway and this progress was independent of the Hippo pathway.

Reproductive history does not compromise subsequent live birth and perinatal outcome following in-vitro fertilization: analysis of 25 329 first frozen-thawed embryo transfer cycles without preimplantation genetic testing for aneuploidy.

OBJECTIVE: To investigate the effect of women's reproductive history on live-birth rate and perinatal outcome after first frozen-thawed embryo transfer (FET) without preimplantation genetic testing for aneuploidy. METHODS: This was a retrospective cohort study of women who had undergone their first FET cycle between January 2014 and December 2020 at a university-affiliated fertility center. No transferred embryo underwent preimplantation genetic testing for aneuploidy. The women were categorized into five groups based on their reproductive history: no previous pregnancy; previous termination of pregnancy (TOP); previous pregnancy loss; previous ectopic pregnancy (EP); and previous live birth. The women with no previous pregnancy were considered as the reference group. The primary outcome was the live-birth rate and secondary endpoints included rates of positive pregnancy test, clinical pregnancy, pregnancy loss and EP as well as perinatal outcomes such as birth weight and preterm birth. Multivariable logistic regression analyses were used to control for a number of potential confounders, including age, body mass index, education level, duration and cause of infertility, insemination method, type of endometrial preparation, number of embryos transferred, embryo developmental stage, quality of the embryos transferred, year of treatment and endometrial thickness. Additionally, propensity score matching (PSM) was used to check the robustness of the main findings. RESULTS: In total, 25 329 women were included in the final analysis. On univariate analysis, each reproductive-history type except for previous EP was significantly associated with worse pregnancy outcome following in-vitro fertilization (IVF), including rates of positive pregnancy test, clinical pregnancy, pregnancy loss and live birth, when compared with the group of women with no previous pregnancy. However, after correcting for several potential confounders, the differences in rates of live birth, pregnancy loss, positive pregnancy test and clinical pregnancy were no longer significant between the study and control groups on multivariable regression models, while the risk of EP after embryo transfer was elevated among women with a previous TOP or EP. There was no increased risk of adverse perinatal outcome associated with reproductive history compared with the control group. Notably, similar results were obtained from the PSM models, confirming the robustness of the main findings. CONCLUSION: Relative to women without a previous pregnancy, those with a prior TOP, pregnancy loss, EP or live birth did not have compromised live-birth rate or perinatal outcomes following FET without preimplantation genetic testing for aneuploidy, with the exception of an increased risk of EP in those with prior TOP or EP. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.