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 investigate the application value of the teaching evaluation method guided by cultivating "excellent doctors" in the clinical teaching of dermatology and venereology.Methods:A non-simultaneous control study was conducted, and the medical students who received theoretical learning and clinical internship in Department of Dermatology and Venereology, Affiliated Hospital of North Sichuan Medical College, from March 2020 to February 2022, were enrolled as subjects. According to the order of enrollment, 32 students who were enrolled from March 2020 to February 2021 were set up as control group, and 31 students who were enrolled from March 2021 to February 2022 were set up as experimental group. The students in the control group received lecture-based learning, and those in the experimental group received clinical teaching using a teaching and evaluation method guided by cultivating "excellent doctors". After the course ended, the two groups were compared in terms of the scores of theoretical knowledge and operation skills, clinical thinking ability [Self-Assessment of Clinical Reasoning and Reflection (SACRR)], core competence [Mini-Clinical Evaluation Exercise (Mini CEX)], and degree of satisfaction with teaching. SPSS 25.0 software was used to perform the independent samples t-test, the Mann-Whitney U test, the chi-square test, and the rank sum test. Results:One student in the control group voluntarily withdrew from the study, and one student in the experimental group did not complete the contents of internship. Finally, 31 students in the control group and 30 in the experimental group were included in the study. After 4 weeks of internship, compared with the control group, the experimental group had significantly higher scores of theoretical knowledge (88.00±4.30 vs. 85.71±4.12, t=2.12, P=0.040) and operation skills (91.87±3.99 vs. 88.23±3.84, t=3.63, P<0.05). After 4 weeks of internship, compared with the control group, the experimental group had significantly higher information systematization score (47.23±3.11 vs. 45.16±3.00), analysis problem score (34.87±2.30 vs. 31.29±2.30), truth finding score (16.30±1.49 vs. 14.45±1.52), reflective ability score [3.50 (3.00, 4.00) vs. 3.00 (3.00, 3.00)], and total score of SACRR (101.87±4.47 vs. 93.90±4.47), with significant differences between the two groups ( t/ Z=2.65, 6.17, 4.79, 3.15, and 6.96, all P<0.05). After 4 weeks of internship, the experimental group had a significantly better core competence than the control group ( Z=2.12, P=0.030); compared with the control group, the experimental group had significantly higher classroom teaching score (20.17±1.98 vs. 18.45±2.23, t=3.17, P<0.05), clinical practice score (19.83±2.10 vs. 17.65±2.17, t=4.00, P<0.05), learning plan score (18.63±2.24 vs. 17.03±2.15, t=2.85, P<0.05), teaching resource score (20.07±1.82 vs. 18.58±2.00, t=3.04, P<0.05) and total score (78.70±3.67 vs. 71.71±4.13, t=6.98, P<0.05). Conclusions:The application of the teaching and evaluation method guided by cultivating "excellent doctors" in the clinical teaching of dermatology and venereology can improve clinical theoretical knowledge, practical operation skills, clinical thinking ability, and core ability among interns and thus help to improve teaching quality. Therefore, it holds promise for clinical application.

Objective:To evaluate the feasibility and clinical value of pre-treatment non-enhanced chest CT radiomics features and machine learning algorithm to predict the mutation status and subtype (19Del/21L858R) of epidermal growth factor receptor (EGFR) for patients with non-small cell lung cancer (NSCLC).Methods:This retrospective study enrolled 280 NSCLC patients from first and second affiliated hospital of University of South China who were confirmed by biopsy pathology, gene examination, and have pre-treatment non-enhanced CT scans. There are 136 patients were confirmed EGFR mutation. Primary lung gross tumor volume was contoured by two experienced radiologists and oncologists, and 851 radiomics features were subsequently extracted. Then, spearman correlation analysis and RELIEFF algorithm were used to screen predictive features. The two hospitals were training and validation cohort, respectively. Clinical-radiomics model was constructed using selected radiomics and clinical features, and compared with models built by radiomics features or clinical features respectively. In this study, machine learning models were established using support vector machine (SVM) and a sequential modeling procedure to predict the mutation status and subtype of EGFR. The area under receiver operating curve (AUC-ROC) was employed to evaluate the performances of established models.Results:After feature selection, 21 radiomics features were found to be efffective in predicting EGFR mutation status and subtype and were used to establish radiomics models. Three types models were established, including clinical model, radiomics model, and clinical-radiomics model. The clinical-radiomics model showed the best predictive efficacy, AUCs of predicting EGFR mutation status for training dataset and validation dataset were 0.956 (95% CI: 0.952-1.000) and 0.961 (95% CI: 0.924-0.998), respectively. The AUCs of predicting 19Del/L858R mutation subtype for training dataset and validation dataset were 0.926 (95% CI: 0.893-0.959), 0.938 (95% CI: 0.876-1.000), respectively. Conclusions:The constructed sequential models based on integration of CT radiomics, clinical features and machine learning can accurately predict the mutation status and subtype of EGFR.

The constitutive androstane receptor (CAR, NR3I1) belongs to nuclear receptor superfamily. It was reported that CAR agonist TCPOBOP induces hepatomegaly but the underlying mechanism remains largely unknown. Yes-associated protein (YAP) is a potent regulator of organ size. The aim of this study is to explore the role of YAP in CAR activation-induced hepatomegaly and liver regeneration. TCPOBOP-induced CAR activation on hepatomegaly and liver regeneration was evaluated in wild-type (WT) mice, liver-specific YAP-deficient mice, and partial hepatectomy (PHx) mice. The results demonstrate that TCPOBOP can increase the liver-to-body weight ratio in wild-type mice and PHx mice. Hepatocytes enlargement around central vein (CV) area was observed, meanwhile hepatocytes proliferation was promoted as evidenced by the increased number of KI67

Objective:To comprehensively evaluate the validity of Morse Fall Scale for predicting the fall risk in hospitalized patients by using Meta-analysis.Methods:Cochrane library, PubMed, Web of science, Embase database, China Biology Medicine disc (CBMdisc) , CNKI, Wanfang Database and VIP database were searched to collect research literatures on Morse Fall Scale predicting fall risk, and the search time limit was from the establishment of databases to September 30, 2019. Quality Assessment of Diagnostic Accuracy Studies (QUADAS) was used to evaluate the quality of included literatures, and Meta-Disc 1.4 software was used for data analysis.Results:Finally, 20 articles were included, involving a total of 48 947 patients. Heterogeneity tests revealed heterogeneity in the included studies. Calculated by a random effect model, the pooled sensitivity was 0.75 (95% CI 0.73 to 0.77) , pooled specificity was 0.64 (95% CI 0.64 to 0.64) , pooled positive likelihood ratio was 2.45 (95% CI 1.97 to 3.03) , pooled negative likelihood ratio was 0.39 (95% CI 0.29 to 0.52) , pooled diagnostic odds ratio was 6.58 (95% CI 4.13 to 10.46) , and the pooled area under the receiver operating characteristic curve was 0.78 ( SE=0.026) . Conclusions:As a separate assessment index, Morse Fall Scale has a moderate validity in in predicting the fall risk in inpatients.

Objective: To identify a pig model with bilateral external ear defects accompanied by aural atresia and investigate its application in plastic surgery. Methods: Erhualian×Shaziling F₂ pig inbreeding population was introduced, and examination of external ear morphology was conducted in all individuals. Temporal computed tomography scanning and mutational detection of HOXA1 gene were conducted in one affected and one normal individuals. Results: In Erhualian×Shaziling F₂ pig inbreeding population, there were 57 normal and 18 affected individuals among the 75 pigs. Affected subjects presented bilateral external ear defects accompanied by aural atresia; temporal computed tomography scanning showed bilateral aural atresia and dysplasiaof middle ear; and gene detection identified homozygous mutation of HOXA1 gene. Conclusions Pig model with HOXA1 gene homozygous mutation resembles human microtia at different levels. Our findings provide the theoretical basis for its application to study further pathological mechanism for human microtia.

Objective To assess the value of contrast enhanced mammography (CESM) in the detection of breast cancer. Methods A total of 145 patients who were suspected of breast abnormalities by clinical examination or ultrasound were prospectively collected. All patients underwent bilateral breast CESM and MRI examinations. Breast CESM and MRI examination were completed in the same week. The pathological specimens were analyzed and the maximum diameters of pathological lesions were measured. The lesions were observed on low energy(LE), CESM and MRI images, and then the maximum diameters of lesions on the above images were measured. Using pathology results as the gold standard, the diagnostic efficacy of LE, CESM and MRI were analyzed by ROC curve, and Z test was used to compare the areas under the ROC curves among different imaging methods. Bland-Altman method was used to analyze the consistency of the maximum diameters of the lesions obtained with different imaging methods. Results One hundred and fifty three lesions were found in 145 patients, in which 36 were benign and 117 were malignant. The LE, CESM and MRI showed 140, 151 and 149 lesions respectively, and the qualitative diagnostic errors were 25, 8 and 11, respectively. The areas under ROC curves of LE, CESM and MRI were 0.87, 0.96 and 0.97 respectively. There was significant difference of the area under ROC curve between CESM and LE, so did the MRI and LE (P<0.05), but there was not significant difference between CESM and MRI (P=0.51). The sensitivity, specificity and accuracy in the diagnosis of malignant breast lesions were 88.98%, 65.71% and 83.66% for LE, while they were 95.80%, 91.18% and 94.77% for CESM, 94.17%, 87.88%and 92.81%for MRI. The average difference of diameters between LE, CESM, MRI and pathologic size was-1.7, 1.1 and 0.3 mm, respectively, with 95%consistency interval range of-18.6 to 15.1,-9.8 to 12.1,-10.6 to 11.2 mm, respectively. There was best consistency between the pathological size and the size on MRI. Conclusion CESM can significantly improve the diagnostic efficacy of breast lesions, which is comparable with MRI.

Objective To establish a patient-derived xenografts (PDX) mouse model of liver cancer (LC) and to explore its role in precision medicine.Methods PDX model was established by subcutaneous implantation of tumor tissues in NCG mice.The morphological structure of tumor tissue was exaimed using HE staining.Fifteen BALB/c nude mice were subcutaneously inoculated with tumor cell suspension from the PDX models.The xenograft mice were randomly divided into 5-fluorouracil (5-FU) group, sorafenib group and negative control group.The tumor volume and body weight of the tumor-bearing mice were measured regularly, the tumor inhibition rate was calculated and the curative effect was evaluated.Results The success rate was 33.3% (6/18) in the establishment of liver cancer PDX mouse model, and the model well retained the characteristics of the primary tumor.In one case of PDX mouse model, the tumor inhibition rates of 5-FU and sorafenib group were 63.7% and 29.6%, with a statistically significant differece between them (P< 0.05), and there was no significant difference between the sorafenib group and negative control group, consistent with clinical observation.Conclusions The PDX mouse model of liver cancer can maintain the histological structure of primary tumor, and can be applied to precision medicine for patients with liver cancer.

Objective To study the clinical efficacy of the combination of sephedex and docetaxel used in transcatheter arterial chemoembolization (TACE) for clinical treatment of primary liver cancer.Methods 120 patients with primary liver cancer in our hospital were divided into the experimental group and the control group randomly and equally, the 60 cases in experimental group were treated with sephedex suspensoid (Sephedex, G-50, 300-500 μm) and docetaxel-iodized oil, while other 60 cases in control group were treated with docetaxel-iodized oil suspension liquid.Results The success rate of surgical intubation in the two groups was 100%.After an average follow-up of 12 months, the postoperative tumor diameter of the experimental group was reduced by (4.4±1.4) cm, while that of the control group was (1.8±1.0) cm;The overall response rate was 70% in the experimental group in contrast to 30% in the control group;the alpha fetal protein (AFP) value was decreased by (33.2±15.2) μg/L in the experimental group and (10.4±9.8) μg/L in the control group.Conclusion The combination of sephedex, docetaxel suspensoid and iodized oil shows great potential in TACE treatment of primary liver cancer, from which the treatment effect can be improved significantly.