Given that ovarian stimulation is vital for assisted reproductive technology (ART) and results in elevated serum estrogen levels, exploring the impact of elevated estrogen exposure on oocytes and embryos is necessary. We investigated the effects of various ovarian stimulation treatments on oocyte and embryo morphology and gene expression using a mouse model and estrogen-treated mouse embryonic stem cells (mESCs). Female C57BL/6J mice were subjected to two types of conventional ovarian stimulation and ovarian hyperstimulation; mice treated with only normal saline served as controls. Hyperstimulation resulted in high serum estrogen levels, enlarged ovaries, an increased number of aberrant oocytes, and decreased embryo formation. The messenger RNA (mRNA)‍-sequencing of oocytes revealed the dysregulated expression of lysine-specific demethylase 6b (Kdm6b), which may be a key factor indicating hyperstimulation-induced aberrant oocytes and embryos. In vitro, Kdm6b expression was downregulated in mESCs treated with high-dose estrogen; treatment with an estrogen receptor antagonist could reverse this downregulated expression level. Furthermore, treatment with high-dose estrogen resulted in the upregulated expression of histone H3 lysine 27 trimethylation (H3K27me3) and phosphorylated H2A histone family member X (γ-H2AX). Notably, knockdown of Kdm6b and high estrogen levels hindered the formation of embryoid bodies, with a concomitant increase in the expression of H3K27me3 and γ-H2AX. Collectively, our findings revealed that hyperstimulation-induced high-dose estrogen could impair the demethylation of H3K27me3 by reducing Kdm6b expression. Accordingly, Kdm6b could be a promising marker for clinically predicting ART outcomes in patients with ovarian hyperstimulation syndrome.
Female ; Mice ; Demethylation/drug effects* ; Embryonic Stem Cells ; Estrogens/administration & dosage* ; Gene Expression/drug effects* ; Histones/metabolism* ; Jumonji Domain-Containing Histone Demethylases/metabolism* ; Mice, Inbred C57BL ; Oocytes ; Ovary/drug effects* ; Reproductive Techniques, Assisted ; Animals

Objective:To explore the role of LncRNA NKILA/NF-κB signal pathway in the injury of keratinocytes in oral lichen planus(OLP).Methods:Immortalized human epidermal cells(HaCaTs)were induced by bacterial lipopolysaccharide(LPS)to establish an in vitro cell model of OLP.HaCaTs stably overexpressing NKILA were constructed by lentivirus method.HaCaTs were divided into 4 groups:Control group,Control+LPS group,empty vector infected with lentivirus(NC)+LPS group,overexpressed NKILA(OE)+LPS group.Cell proliferation,apoptosis,total superoxide dismutase(SOD)activity,lipid malondialdehyde oxide(MDA),reactive oxygen species(ROS),expression of related inflammatory factors,p65(nuclear,mass)and NF-κB signaling pathway related protein expression and p65 expression and localization were respectively detected.Results:Compared with Control group,the expression of NKILA,cell proliferation activity and SOD enzyme activity in Control+LPS group were significantly de-creased,while the apoptosis rate,MDA,ROS,IL-6,IL-1β,TNF-α and p65(nuclear and plasma)expression levels were signifi-cantly up-regulated(P＜0.05).Compared with Control+LPS group,the cell proliferation activity and SOD activity were increased in OE+LPS group,and the expression levels of cell apoptosis,MDA,ROS,IL-6,IL-1β,TNF-α and p65(nuclear and plasma)were significantly decreased(P＜0.05),and the localization of p65 protein in the nucleus was significantly decreased in OE+LPS group.Conclusion:LncRNA NKILA may reduce the damage of keratinocytes in oral lichen planus by inhibiting NF-κB signal pathway.

Objective:To explore the efficacy and safety of B-Raf proto-oncogene, serine/threonine kinase (BRAF) inhibitor and epidermal growth factor receptor (EGFR) inhibitor combined with immune checkpoint inhibitor in microsatellite stable (MSS) BRAF V600E metastatic colorectal cancer (mCRC) patients.Methods:The data and outcomes of mCRC patients with MSS BRAF V600E who received BRAF inhibitor, EGFR inhibitor combined with immune checkpoint inhibitor in Tianjin Medical University Cancer Hospital from May 2022 to April 2024 were retrospectively collected.Results:A total of 12 mCRC patients were included in this study, the objective response rate was 50.0%, the disease control rate was 66.7%, and the median disease control time of patients who achieved objective response was 8.0 months. The median progression-free survival was 6.8 months and the median overall survival was 8.4 months. Overall adverse reactions were controllable, the most common treatment-related adverse events were fatigue (8 cases), fever (5 cases), and rash (4 cases). There were no grade 4 adverse event, serious adverse event, and treatment-related death.Conclusion:BRAF inhibitor and EGFR inhibitor combined with immune checkpoint inhibitor show good efficacy and controllable safety in BRAF V600E mCRC patients.

Objective:To explore the efficacy and safety of B-Raf proto-oncogene, serine/threonine kinase (BRAF) inhibitor and epidermal growth factor receptor (EGFR) inhibitor combined with immune checkpoint inhibitor in microsatellite stable (MSS) BRAF V600E metastatic colorectal cancer (mCRC) patients.Methods:The data and outcomes of mCRC patients with MSS BRAF V600E who received BRAF inhibitor, EGFR inhibitor combined with immune checkpoint inhibitor in Tianjin Medical University Cancer Hospital from May 2022 to April 2024 were retrospectively collected.Results:A total of 12 mCRC patients were included in this study, the objective response rate was 50.0%, the disease control rate was 66.7%, and the median disease control time of patients who achieved objective response was 8.0 months. The median progression-free survival was 6.8 months and the median overall survival was 8.4 months. Overall adverse reactions were controllable, the most common treatment-related adverse events were fatigue (8 cases), fever (5 cases), and rash (4 cases). There were no grade 4 adverse event, serious adverse event, and treatment-related death.Conclusion:BRAF inhibitor and EGFR inhibitor combined with immune checkpoint inhibitor show good efficacy and controllable safety in BRAF V600E mCRC patients.

Objective:To explore the role of LncRNA NKILA/NF-κB signal pathway in the injury of keratinocytes in oral lichen planus(OLP).Methods:Immortalized human epidermal cells(HaCaTs)were induced by bacterial lipopolysaccharide(LPS)to establish an in vitro cell model of OLP.HaCaTs stably overexpressing NKILA were constructed by lentivirus method.HaCaTs were divided into 4 groups:Control group,Control+LPS group,empty vector infected with lentivirus(NC)+LPS group,overexpressed NKILA(OE)+LPS group.Cell proliferation,apoptosis,total superoxide dismutase(SOD)activity,lipid malondialdehyde oxide(MDA),reactive oxygen species(ROS),expression of related inflammatory factors,p65(nuclear,mass)and NF-κB signaling pathway related protein expression and p65 expression and localization were respectively detected.Results:Compared with Control group,the expression of NKILA,cell proliferation activity and SOD enzyme activity in Control+LPS group were significantly de-creased,while the apoptosis rate,MDA,ROS,IL-6,IL-1β,TNF-α and p65(nuclear and plasma)expression levels were signifi-cantly up-regulated(P＜0.05).Compared with Control+LPS group,the cell proliferation activity and SOD activity were increased in OE+LPS group,and the expression levels of cell apoptosis,MDA,ROS,IL-6,IL-1β,TNF-α and p65(nuclear and plasma)were significantly decreased(P＜0.05),and the localization of p65 protein in the nucleus was significantly decreased in OE+LPS group.Conclusion:LncRNA NKILA may reduce the damage of keratinocytes in oral lichen planus by inhibiting NF-κB signal pathway.

Objective:To explore and analyze the characteristics and influencing factors of language development in children with attention deficit hyperactivity disorder (ADHD).Methods:A case-control study was used, from May 2021 to August 2023, patients diagnosed with attention deficit hyperactivity disorder (ADHD) were enrolled in the mental health clinic of the Children′s Hospital Affiliated to the Capital Institute of Pediatrics. The language ability of 272 children with ADHD and 117 healthy children who underwent physical examination in children′s health center during the same period were tested by Diagnostic Receptive and Expressive Assessment of Mandarin-Comprehensive (DREAM-C), and the development levels of total language, receptive, expressive, semantics and syntax of the two groups were compared by independent sample t-test. The influential factors of language lag in children with ADHD were analyzed by univariate χ2 analysis and multiple logistic regression. Results:There were 272 children with ADHD, including 206 males and 66 females, with an age range of 6-8 (7.29±1.17) years. While in the control group, there were 117 healthy children, including 91 males and 26 females, with an age range of 6-8 (7.02±0.82) years. The average scores of total language, expressive and syntax of ADHD children were lower than those of healthy children [(92.73±12.47/96.36±11.04), t=-2.857, P<0.05; (84.49±13.24/87.78±15.25), t=-2.029, P<0.05; (87.93±10.26/90.27±11.05), t=2.022, P<0.05]. Univariate χ2 analysis showed that disharmonious family relationship ( χ2=4.183, P<0.05), the main caregivers were non-parents ( χ2=9.121, P<0.05), early screen exposure ( χ2=3.889, P<0.05), ADHD family history ( χ2=5.423, P<0.05) were influential factors of language development lag in ADHD children. The results of multivariate logistic regression model analysis showed that cesarean section ( OR=2.137, 95% CI: 1.078-4.379, P=0.030), disharmonious family relationship ( OR=2.659, 95% CI: 1.178-5.999, P=0.019), early screen exposure ( OR=3.556, 95% CI: 1.127-11.213, P=0.030), ADHD family history ( OR=1.959, 95% CI: 1.058-3.630, P=0.033) were risk factors for comorbidities of language development in children with ADHD. Conclusion:The total language ability, expressive and syntax scores of ADHD children lag behind those of healthy children. The delayed language development of ADHD children is related to delivery mode, family relationship, the main caregivers, early screen exposure, family history of ADHD.

Objective:To explore and analyze the characteristics and influencing factors of language development in children with attention deficit hyperactivity disorder (ADHD).Methods:A case-control study was used, from May 2021 to August 2023, patients diagnosed with attention deficit hyperactivity disorder (ADHD) were enrolled in the mental health clinic of the Children′s Hospital Affiliated to the Capital Institute of Pediatrics. The language ability of 272 children with ADHD and 117 healthy children who underwent physical examination in children′s health center during the same period were tested by Diagnostic Receptive and Expressive Assessment of Mandarin-Comprehensive (DREAM-C), and the development levels of total language, receptive, expressive, semantics and syntax of the two groups were compared by independent sample t-test. The influential factors of language lag in children with ADHD were analyzed by univariate χ2 analysis and multiple logistic regression. Results:There were 272 children with ADHD, including 206 males and 66 females, with an age range of 6-8 (7.29±1.17) years. While in the control group, there were 117 healthy children, including 91 males and 26 females, with an age range of 6-8 (7.02±0.82) years. The average scores of total language, expressive and syntax of ADHD children were lower than those of healthy children [(92.73±12.47/96.36±11.04), t=-2.857, P<0.05; (84.49±13.24/87.78±15.25), t=-2.029, P<0.05; (87.93±10.26/90.27±11.05), t=2.022, P<0.05]. Univariate χ2 analysis showed that disharmonious family relationship ( χ2=4.183, P<0.05), the main caregivers were non-parents ( χ2=9.121, P<0.05), early screen exposure ( χ2=3.889, P<0.05), ADHD family history ( χ2=5.423, P<0.05) were influential factors of language development lag in ADHD children. The results of multivariate logistic regression model analysis showed that cesarean section ( OR=2.137, 95% CI: 1.078-4.379, P=0.030), disharmonious family relationship ( OR=2.659, 95% CI: 1.178-5.999, P=0.019), early screen exposure ( OR=3.556, 95% CI: 1.127-11.213, P=0.030), ADHD family history ( OR=1.959, 95% CI: 1.058-3.630, P=0.033) were risk factors for comorbidities of language development in children with ADHD. Conclusion:The total language ability, expressive and syntax scores of ADHD children lag behind those of healthy children. The delayed language development of ADHD children is related to delivery mode, family relationship, the main caregivers, early screen exposure, family history of ADHD.

BACKGROUND:Ligaments are important structures in maintaining the stability of the lumbar spine,and these structures are prone to degradation due to the generated mechanical stress.However,there are few studies on ligament injuries. OBJECTIVE:To determine the range of motion and stress of each ligament in the state of motion based on a three-dimensional finite element model,and to systematically explore the influence of ligament injury on the stability of the lumbar spine and its biomechanical significance. METHODS:The L4-L5 lumbar finite element model was established.All free forces on the lower surface of L5 were constrained,and a torque of 5 N·m was applied to simulate the motion states of the lumbar spine.Progressive ligament damage was simulated by changing Young's modulus of the ligament. RESULTS AND CONCLUSION:(1)The extension range of motion of most ligament injuries increased significantly.In contrast,there was no significant change in the lateral bending range of motion.(2)The range of motion of capsular ligament injury increased significantly in flexion,extension and lateral bending.The extension range of motion increased significantly after the anterior longitudinal ligament injury.Intertransverse ligament injury resulted in a significant increase in the lateral bending range of motion.(3)After a single ligament injury,the most significant change in range of motion was observed during extension.After a single ligament injury,the stress of the remaining ligaments increased,especially the capsular ligament.The stress changes of the interspinous ligament and ligamentum flavum were the least obvious.Ligament stress changes least in lateral bending and most in torsion.(4)Ligament damage did not result in major changes in disc pressure,indicating that ligament injury leads to an increased range of motion of the lumbar spine and affects the stability of the lumbar spine.(5)Capsular ligament was stable in flexion,extension and lateral bending.The anterior longitudinal ligament showed a stable extension;the intertransverse ligament stabilizes the lateral curve.(6)Extension exercise is sensitive to a ligament injury,and the pathological changes of the ligament can be examined by extension exercise.(7)Stress compensation was given to the remaining ligaments to maintain the stability of the lumbar spine after a single ligament injury.(8)Interspinous ligament and ligamentum flavum injuries have the least impact on the peripheral ligaments,while capsular ligament injuries have the greatest impact on the peripheral ligaments.(9)The ligament injury has the least effect on the residual ligament stress during lateral bending exercise,while it has the greatest effect on the ligament stress during the twisting exercise.Patients with ligament injury should avoid twisting exercises.Ligament injuries do not affect disc pressure.

Objective:To evaluate whether index of microcirculatory resistance(IMR)is associated with left ventricular(LV)remodeling in acute anterior ST elevation myocardial infarction(STEMI)pa-tients undergoing primary percutaneous coronary intervention(PPCI).Methods:This was a single-center retrospective cohort study.The patients with first anterior STEMI who received PPCI from January 2014 to August 2017 in Peking University Third Hospital was enrolled.After PPCI,IMR was measured immediately by using pressure/temperature guidewire.The success rate of IMR measurement was 100％.Also we collected some related clinical data from the medical records and laboratory results.Infarct size[assessed as creatine kinase(CK)peak],echocardiography at baseline and 1 year follow-up were as-sessed.LV adverse remodeling(LVAR)was defined as ≥20％increase in LV end-diastolic volume(LVEDV).Results:A total of forty-three patients were enrolled,with an average age of(58.7±12.4)years.The patients were divided into two groups as IMR ≤25 and IMR＞25 by normal values recommen-ded by previous literature.Compared with IMR ≤25 group,IMR＞25 group had a higher percentage of initial thrombolysis in myocardial infraction(TIMI)grade 0(95.7％vs.65.0％,P=0.029),higher serum CK peak value[4 090(383,15 833)vs.1 580(396,5 583),P=0.004].The IMR＞25 group suffered higher rates of ventricular aneurysm(30.4％vs.5.0％,P=0.021).There was no difference in LVEDV[(111.0±18.8)mL vs.(115.0±23.6)mL,P=0.503]between the two groups 1 day after MI,but after 1 year,LVEDV in IMR＞25 group was significantly higher than in IMR≤25 group[(141.5± 33.7)mLvs.(115.9±27.9)mL,P=0.018].The incidence of LVAR was more significant in IMR＞25 group(47.4％vs.11.8％,P=0.024).Binary Logistics regression showed that IMR[B=0.079,exp(B)(95％CI)=1.082(1.018-1.149),P=0.011]and serum triglyceride level[B=1.610,exp(B)(95％CI)=5.005(1.380-18.152),P=0.014]were the predictors of LVAR 1 year after MI.IMR had a good predictive value for LVAR 1 year after MI[area under the curve(AUC)=0.749,P=0.019],IMR＞29 was a good cutoff value with sensitivity 81.8％and specificity 68.0％.Conclusion:Our study elaborates that immediate measurement of IMR after PPCI in patients with STEMI can reflect the microvas-cular function.And IMR could be used as a quantitative biomarker to predict LVAR after STEMI.

Objective:To explore the prognosis efficacy of psycho-cardiological therapy and management on patients with coronary atherosclerosis disease (CAD).Methods:This was a clinical randomized controlled study. This study included inpatients with CAD at the cardiology department in Beijing Anzhen Hospital, Capital Medical University from August 2021 to January 2024. The patients enrolled in this study were asked for basic information, and received measurements for depression, anxiety, sleep quality and living quality by the scales of Patient Health Questionnaire-9 (PHQ-9), General Anxiety Disorder scale-7 (GAD-7), Athens Insomnia Scale (AIS), EuroQol 5-dimension 5-level (EQ-5D-5L) respectively. The patients were randomly grouped into a regular treatment group and a psycho-cardiological treatment group which included WeChat management or antidepressant/antianxiety medical therapy according to the situation. After the patients discharging from hospital for 2, 4, 12, 24, 48, 72, and 96 weeks, professional cardiovascular doctors would follow up by telephone, WeChat, and outpatient department, including scales (2-48 weeks), and cardiac events (2-96 weeks). Kaplan-Meier survival curve and multivariate Cox proportional hazards model were used for analyzing the association between psycho-cardiological treatment and cardiac events.Results:This study recruited a total of 552 patients with CAD, aged 61.0(54.0, 67.0) years, and 379 (68.7%) were male. There were 279(50.5%) in the regular treatment group and 273(49.5%) in the psycho-cardiological treatment group. After treatment for 4, 12 and 48 weeks, the PHQ-9 score in psycho-cardiological was significantly lower than the regular treatment group; After treatment for 12 weeks, the EQ-5D-5L effective value in psycho-cardiological group was higher than the regular treatment group; After treatment for 2, 4, 12, 24 and 48 weeks, the EQ-5D-5L VAS score in psycho-cardiological group was higher than the regular therapy group (all P<0.05). The Kaplan-Meier survival curve showed that, during the different follow-up periods, the rate of cardiac events in psycho-cardiological treatment group was lower than regular treatment group (log-rank P<0.001). The multivariate Cox proportional hazards model adjusted the factor of age, the psycho-cardiological treatment contributed to reducing the cardiac events rate by 80.3% ( HR=0.197, 95% CI: 0.067-0.582, P=0.003). Conclusion:Psycho-cardiological treatment is beneficial for improving psychological stress, living quality, and reducing cardiac events, and helps to improve prognosis and psycho-cardiological rehabilitation in CAD patients.