Objective To construct intrauterine adhesion (IUA) mouse models induced by two different concentrations of ethanol injury, compare the phenotypes, and optimize a more stable IUA modeling method. Methods Twenty 8-week-old female C57BL/6N mice were randomly divided into two groups: the 95% ethanol injury group and the 50% ethanol injury group. Using a self-control method, the left uterine horn was infused with ethanol to establish the IUA model, while the right uterine horn was infused with saline as the sham operation. Five mice from each group were euthanized on day 7 and 15 after modeling, and uterine tissues were collected. Hematoxylin-eosin (HE) staining was used to observe the endometrial pathology, and Masson staining was used to assess the degree of endometrial fibrosis. Quantitative real-time PCR was employed to detect the expression levels of fibrosis markers and pro-inflammatory factors in the uterine tissues. Results Compared to the sham operation, these two ethanol injury led to a significant reduction in elasticity of the uterus, an increase in inflammatory infiltration, and a marked increase in the degree of fibrosis on day 7 after modeling (P<0.05). The 95% ethanol injury group showed a significant decrease in endometrial thickness (P<0.05), whereas no significant change was observed in the 50% ethanol injury group when compared to the sham operation (P>0.05). The expression levels of fibrotic marker molecules collagen type Ⅳ alpha 1 chain (Col4A1), α-smooth muscle actin (α-SMA), transforming growth factor-β (TGF-β), and pro-inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were significantly elevated in the 50% ethanol injury group when compared to the sham operation (P<0.05), although there was an increasing trend of the same markers in the 95% ethanol injury group, the differences were not statistically significant (P>0.05). On day 15 after modeling, the histopathological changes in both ethanol injury groups were not significant when compared to the sham operation, the expression levels of Col4A1, TGF-β, TNF-α and IL-1β remained significantly higher in the 50% ethanol injury group (P<0.05), while only IL-1β was significantly elevated in the 95% ethanol injury group (P<0.05). Conclusion Uterine infusion with 95% ethanol results in more marked histopathological changes in the IUA mouse model compared to the 50% ethanol injury group. The 95% ethanol injury model is suitable for histopathological studies. However, the 50% ethanol injury group shows higher expression levels of fibrosis markers and pro-inflammatory factors compared to the 95% ethanol injury group, suggesting that the 50% ethanol injury model is more suitable for molecular pathological study.

The continuous emergence of SARS-CoV-2 variants as well as other potential future coronavirus has challenged the effectiveness of current COVID-19 vaccines. Therefore, there remains a need for alternative antivirals that target processes less susceptible to mutations, such as the formation of six-helix bundle (6-HB) during the viral fusion step of host cell entry. In this study, a novel high-throughput screening (HTS) assay employing a yeast-two-hybrid (Y2H) system was established to identify inhibitors of HR1/HR2 interaction. The compound IMB-9C, which achieved single-digit micromolar inhibition of SARS-CoV-2 and its Omicron variants with low cytotoxicity, was selected. IMB-9C effectively blocks the HR1/HR2 interaction in vitro and inhibits SARS-CoV-2-S-mediated cell-cell fusion. It binds to both HR1 and HR2 through non-covalent interaction and influences the secondary structure of HR1/HR2 complex. In addition, virtual docking and site-mutagenesis results suggest that amino acid residues A930, I931, K933, T941, and L945 are critical for IMB-9C binding to HR1. Collectively, in this study, we have developed a novel screening method for HR1/HR2 interaction inhibitors and identified IMB-9C as a potential antiviral small molecule against COVID-19 and its variants.

Objective:To aid in the detection of thyroid cancer by using deep learning to differentiate the unique bioimpedance parameter patterns of different thyroid tissues.Methods:An electrical impedance system was designed to measure 331 ex-vivo thyroid specimens from 321 patients during surgery. The impedance data was then analyzed with one dimensional convolution neural (1D-CNN) combining with long short-term memory (LSTM) network models of deep learning. In the process of analysis, we assigned 80% of the data to training set (1072/1340) and the remaining 20% data to the test set (268/1340). The performance of final model was assessed using receiver operating characteristic (ROC) curves. In addition, sensitivity, specificity, positive predictive value, negative predictive value, Youden index were applied to compare impedance model with ultrasound results.Results:The ROC curve of the two-classification (malignant /non-malignant tissue) model showed a good performance (area-under-the-curve AUC=0.94), with an overall accuracy of 91.4%. To better fit clinical practice, we further performed a three-classification (malignant/ benign/ normal tissue) model, of which the areas under ROC curve were 0.91, 0.85, 0.92 for normal, benign, and malignant group, respectively. The results indicated that the area under micro-average ROC curve and the macro-average ROC curve were 0.91 and 0.90, respectively. Moreover, compared with ultrasound, the impedance model exhibited higher specificity.Conclusions:A deep learning model (CNN-LSTM) trained by thyroid electrical impedance spectroscopy (EIS) parameters shows an excellent performance in distinguishing among different in-vitro thyroid tissues, which is promising for applications. In future clinical utility, our study does not replace existing tests, but rather complements others, thus contributing to therapeutic decision-making and management of thyroid disease.

Rapidly increasing intraocular pressure(IOP)is a typical manifestation of acute angle-closure glaucoma and an important cause of ocular tissue damage, vision loss and even blindness in glaucoma patients. The sharp increase of intraocular pressure in a short period of time in acute angle-closure glaucoma will cause characteristic damage to the structure and function of retina, choroid and optic nerve. Currently, the diagnosis and evaluation of the course of glaucoma is largely dependent on the state of high IOP, changes in the optic nerve and visual field damage, but irreversible damage to the fundus has already been made in glaucoma patients by this time. The microstructural changes in the posterior segment of the eye are more sensitive to high IOP and often appear before optic nerve and visual field damage, which can indicate the damage of high IOP to the eye earlier. Through the evaluation of the imaging characteristics of the posterior segment of the eye, the morphological characteristics that affect the prognosis of glaucoma can be explored, which is clinically important for the early diagnosis of glaucoma.

Retinopathy of prematurity(ROP), an abnormal vascular proliferative retinopathy of prematurity, is a serious condition that can lead to retinal detachment or blindness. With the development of neonatal medicine, the survival rate of low birth weight and low gestational age infants has been increasing, as well as the incidence of ROP. Therefore, studying ROP's pathogenesis and influencing factors is of great clinical importance. Numerous studies have been conducted on the risk factors for ROP, including gestational age, oxygen intake, mode of delivery, neonatal bronchopulmonary dysplasia, and the use of surfactants. At present, it is widely accepted both at home and abroad that preterm birth, low birth weight, and high oxygen concentration after birth are independent risk factors for ROP. In recent years, more and more scholars have found that abnormalities in blood indicators in preterm infants may be associated with the development of ROP. This article reviews the effects of platelets, haemoglobin, blood glucose, inflammatory cells, and lipids on ROP, providing a reference for identifying and preventing risk factors for ROP.

Oral diseases concern almost every individual and are a serious health risk to the popula-tion.The restorative treatment of tooth and jaw defects is an important means to achieve oral function and support the appearance of the contour.Based on the principle of"learning from the nature",Deng Xu-liang's group of Peking University School and Hospital of Stomatology has proposed a new concept of"microstructural biomimetic design and tissue adaptation of tooth/jaw materials"to address the worldwide problems of difficulty in treating dentine hypersensitivity,poor prognosis of restoration of tooth defects,and vertical bone augmentation of alveolar bone after tooth loss.The group has broken through the bottle-neck of multi-stage biomimetic technology from the design of microscopic features to the enhancement of macroscopic effects,and invented key technologies such as crystalline/amorphous multi-level assembly,ion-transportation blocking,and multi-physical properties of the micro-environment reconstruction,etc.The group also pioneered the cationic-hydrogel desensitizer,digital stump and core integrated restora-tions,and developed new crown and bridge restorative materials,gradient functionalisation guided tissue regeneration membrane,and electrically responsive alveolar bone augmentation restorative membranes,etc.These products have established new clinical strategies for tooth/jaw defect repair and achieved inno-vative results.In conclusion,the research results of our group have strongly supported the theoretical im-provement of stomatology,developed the technical system of oral hard tissue restoration,innovated the clinical treatment strategy,and led the progress of the stomatology industry.

Objective: To construct a prediction model for preeclampsia (PE) risk in twin-pregnant women, so as to provide the basis for early screening and prevention of PE. Methods: A total of 467 twin-pregnant women who underwent prenatal examination and delivered at Huzhou Maternal and Child Health Hospital were selected. Sixty cases with preeclampsia (PE) were included in the case group, and 60 women without PE were included in the control group. General information, blood biochemical indicators and uterine artery resistance index (UtA-RI) were collected. A logistic regression model was used to screen predictive factors and establish a nomogram. The Bootstrap method was performed for the internal validation; the receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis were employed to evaluate the discrimination, calibration and clinical utility of the nomogram, respectively. Results: In the case group, there were 47 individuals (78.33%) aged younger than 35 years, 21 individuals (35.00%) with pre-pregnancy body mass index (BMI) of 25 kg/m2 and above, and 33 individuals (55.00%) with in vitro fertilization. In the control group, there were 57 individuals (95.00%) aged younger than 35 years, 8 individuals (13.33%) with pre-pregnancy BMI of 25 kg/m2 and above, and 39 individuals (65.00%) with natural pregnancy. Multivariable logistic regression analysis identified age, pre-pregnancy BMI, method of conception, placental growth factor (PLGF) and UtA-RI as risk prediction factors for PE in twin-pregnant women. The established nomogram had an area under the ROC curve of 0.827 (95%CI: 0.755-0.899), a sensitivity of 0.767, a specificity of 0.733, a good discrimination and calibration, and a relatively high clinical net benefit. Conclusion The nomogram established by age, pre-pregnancy BMI, method of conception, PLGF and UtA-RI has a good predictive value for the risk of PE in twin-pregnant women.

Objective:To investigate the predictive value of serum uric acid/albumin ratio (sUAR) for acute kidney injury (AKI) after cardiac valve surgery.Methods:The clinical data of adult patients undergoing cardiac valve surgery under cardiopulmonary bypass from January 2021 to December 2021 from the Heart Center of Henan Provincial People's Hospital were collected retrospectively, and the sUAR was calculated. All patients were divided into AKI group and non-AKI group according to whether AKI occurred within 7 days after cardiac valve surgery, and the differences of clinical data between the two groups were compared. Multivariate logistic regression model was used to analyze the independent correlation factors of AKI after cardiac valve surgery. The receiver operating characteristic (ROC) curve was used to evaluate the performance of relevant indicators.Results:A total of 422 patients were enrolled, including 194 females (46.0%), 141 hypertension patients (33.4%) and 172 atrial fibrillation patients (40.8%). They were 57 (50, 65) years old. Their sUAR was 8.13 (6.57, 9.54) μmol/g, and hemoglobin was 135 (125, 145) g/L. There were 142 cases in AKI group and 280 cases in non-AKI group, and the incidence of AKI after cardiac valve surgery was 33.6%. Age, atrial fibrillation rate, baseline serum creatinine, N terminal pro B type natriuretic peptide, serum urea,serum uric acid, blood glucose and sUAR were higher in the AKI group than those in the non-AKI group (all P<0.05), and estimated glomerular filtration rate, lymphocyte count,hemoglobin and serum albumin were lower in the AKI group than those in the non-AKI group (all P<0.05). The median cardiopulmonary bypass time of patients in the AKI group was slightly longer than that in the non-AKI group, but the difference was not statistically significant [159 (125, 192) min vs. 151 (122, 193) min, Z=-0.797, P=0.426], and there were no statistically significant differences in other indicators between the two groups. The results of multivariate logistic regression analysis showed that sUAR ( OR=1.467, 95% CI 1.308-1.645, P<0.001), age ( OR=1.045, 95% CI 1.020-1.072, P<0.001), atrial fibrillation ( OR=2.520, 95% CI 1.580-4.020, P<0.001), hemoglobin ( OR=0.984, 95% CI 0.971-0.997, P=0.015) were the independent correlation factors. ROC curve analysis showed that the area under the curve ( AUC) of sUAR predicting AKI after cardiac valve surgery was 0.710 (95% CI 0.659-0.760, P<0.001) with a sensitivity of 85.2% and specificity of 45.0% for the sUAR cut-off point of 7.28 μmol/g. The AUC for the diagnosis of AKI after cardiac valve surgery was 0.780 (95% CI 0.734-0.825, P<0.001) with a sensitivity of 72.5% and specificity of 71.8% for the combination of sUAR with age, hemoglobin and atrial fibrillation. Conclusions:For patients undergoing cardiac valve surgery under cardiopulmonary bypass, preoperative high sUAR is an independent risk factor for postoperative AKI, and sUAR has a certain predictive value for postoperative AKI.

【Objective】 To explore the causal association between the onset of gastroesophageal reflux disease (GERD) and migraine and to provide genetic evidence, a two-sample bidirectional Mendelian randomization (MR) method was used in this study. 【Methods】 Single nucleotide polymorphism (SNP) information for both samples was obtained from publicly available genome-wide association study (GWAS) databases, in which the appropriate SNPs were selected as instrumental variables, and then bidirectional MR analysis used five MR analysis methods including inverse variance weighting (IVW), MR-Egger regression, weighted median, weighted mode and simple mode methods, followed by sensitivity analysis. 【Results】 IVW showed positive results of forward MR analysis with GERD as exposure [OR=1.398 7, 95%CI (1.181 7-1.655 6), P=9.59×10^-5] , while no positive significance of reverse MR analysis results with migraine as exposure (P>0.05). The same results were obtained in methods other than MR-Egger method. Meanwhile, none of the instrumental variables were found to be horizontally polytomous (P=0.92, P=0.64), and the results were robust after the leave-one-out method to exclude single SNPs. 【Conclusion】 There may be a unidirectional causal association between GERD and migraine, and GERD is a risk factor for migraine development.

Meibomian gland dysfunction is a chronic and diffuse disease of the meibomian glands, characterized by obstruction and(or)abnormal secretion of the terminal ducts. Clinically, it can lead to tear film abnormalities and inflammation of the ocular surface, resulting in symptoms of ocular irritation and potential corneal damage that may impact visual function. Meibomian gland dysfunction can be classified into two types based on meibomian gland secretion: low secretion type and high secretion type. The low secretion type further includes acinar atrophy type and obstruction type. In recent years, research has revealed that patients with diabetes experience chronic damage to their meibomian gland tissue in the early stages of the disease, leading to structural and functional changes. The incidence and severity of meibomian gland dysfunction are higher in diabetic patients. However, there are numerous complex factors contributing to this condition in diabetes patients, and mechanisms remain unclear at present. This article reviews both domestic and international research progress on the pathological mechanism underlying meibomian gland dysfunction in diabetes.