ObjectiveTo explore the possible mechanisms of Shoutai Wan （寿胎丸） in treating recurrent miscarriage （RSA） from the perspective of immune tolerance under the acidic microenvironment at the maternal-fetal interface. MethodsFemale CBA/J mice were randomly divided into normal group， model group， progesterone group， and Shoutai Wan group， with 15 mice in each group. The mice in the normal group and model group were given 0.2 ml distilled water by gavage each day， the Shoutai Wan group given Shoutai Wan decoction 0.15 g/（10 g·d） by gavage， the progesterone group given progesterone tablets 0.44 mg/（10 g·d） by gavage. After gavage for 14 days， the mice were cohabited. Female CBA/J mice in the normal group were mated with male BALB/c mice at a ratio of 2∶1， and female CBA/J mice in the other groups were mated with male DBA/2 mice at a ratio of 2∶1 to establish the RSA mouse model. Vaginal smears were taken from the female mice the next morning， and the appearance of a large number of spermatozoa and the presence of a vaginal plug were considered as the first day of pregnancy. After the appearance of the plug， the mice were continued to be administered according to the previous method until the 10th day of pregnancy. On the 10th day of pregnancy， maternal-fetal interface tissues were collected from each group of mice， and lactate dehydrogenase colorimetric method was used to detect lactate （LA） content； qPCR method and Western blot method were used to detect the expression of immune-related factors interleukin-4 （IL-4）， interferon-gamma （IFN-γ）， transforming growth factor beta 1 （TGF-β1）， and forkhead box protein 3 （Foxp3） mRNA and protein； flow cytometry was used to detect the numbers of helper T lymphocyte 1 （Th1）， helper T lymphocyte 2 （Th2）， regulatory T cell （Treg）， classical macrophage （M1）， and alternative macrophage （M2）. The bivariate Pearson test was used to analyze the correlation between LA content and the numbers of Th1， Th2， Treg， M1， and M2 cells， as well as the correlation between LA content and the expression of IL-4， IFN-γ， TGF-β1， Foxp3 protein， and mRNA. ResultsOn the 10th day of pregnancy， compared with the normal group， the LA content decreased in the model group， and the expression of IL-4， TGF-β1， Foxp3 protein and mRNA in the maternal-fetal interface tissues decreased， while the expression of IFN-γ protein and mRNA increased. The numbers of Th1 and M1 cells increased， while the numbers of Th2， Treg， and M2 cells decreased （P＜0.05 or P＜0.01）. Compared with the model group， the LA content increased in the Shoutai Wan group and progesterone group. The expression of IL-4， TGF-β1， Foxp3 protein and mRNA in the maternal-fetal interface tissues increased， while the expression of IFN-γ protein and mRNA decreased. The numbers of Th1 and M1 cells decreased， while the numbers of Th2， Treg， and M2 cells increased （P＜0.05 or P＜0.01）. The LA content was positively correlated with the numbers of Th2， Treg， and M2 cells， and the expression of IL-4， TGF-β1， Foxp3 protein， and mRNA （P＜0.05 or P＜0.01）； the LA content was negatively correlated with the numbers of Th1， M1 cells， and the expression of IFN-γ protein and mRNA （P＜0.05 or P＜0.01）. ConclusionShoutai Wan may improve immune tolerance by regulating the expression of immune-related factors in the acidic microenvironment at the maternal-fetal interface of RSA model mice， thereby exerting its role in preventing miscarriage.

OBJECTIVE To design and synthesize novel α-naphthylthiol amino acid ester lysine specific demethylase 1(LSD1) inhibitors, evaluate their inhibitory activity with selectivity against LSD1, and explore their binding mechanism through molecular docking and dynamics simulation. METHODS Based on the binding mode of hit compound 3a with LSD1, the α- naphthyl mercapto amino acid ethyl ester small molecule compound were designed by fixing the planar hydrophobic naphthyl ring in the structure, while introducing hydrophilic amino fragment, and they were prepared through a multi-component one-pot cascade reaction. All the compounds were evaluated for their inhibitory activity against LSD1 at concentrations of 5.0 and 1.0 μmol·L–1 using the LSD1 screening platform of research group. The most potent compound was tested for its IC50 value and enzyme selectivity over MAO-A and MAO-B, and its binding mode was investigated through molecular docking and dynamics simulation. RESULTS A total of 13 compounds were obtained, all of which exhibited significant inhibitory effects on LSD1. Among them, nine compounds showed an inhibitory rate of over 50.0% against LSD1 at a concentration of 1.0 μmol·L–1, while compound 3l displaying the best activity with an IC50 value of 0.17 μmol·L–1, 174 times higher than the positive control. It also showed excellent selectivity towards MAO-A and MAO-B. Molecular docking and dynamics simulations indicated that compound 3l inhibited the activity of LSD1 through multiple interactions. CONCLUSION The structures of α-naphthylthiol amino acid ester can serve as lead compounds or active fragments, laying a solid foundation for the subsequent design of LSD1 inhibitors based on structure-oriented drug design.

Objective To investigate the ameliorative effects and potential mechanism of Lithocarpus litseifoliu on renal function and inflammation in mice with hyperuricemic nephropathy(HN).Methods The HN model was established by the combined administration of adenine and potassium oxyzate.The mice were randomly divided into normal control group,model control group,benzbromarone group,and high,medium and low dose groups of Lithocarpus litseifoliu.Different drugs were given to the mice,and their body mass was recorded once a week.The levels of uric acid(UA),creatinine(Cr),urine protein(UP),blood urea nitrogen(BUN)and urine urea nitrogen(UUN)as well as the levels of tumor necrosis factor α(TNF-α)and interleukin 6(IL-6)in serum or urine of each group were collected and measured on the 21st day.Hematoxylin-eosin(HE)staining was performed to observe kidney tissue injury in mice;real-time PCR(RT-PCR)was performed to determine ATP-binding cassette subfamily G member 2(ABCG2),urate transporter protein(URAT1),glucose transporter protein 9(GLUT9),and cytosolic factor NF-κB p50(κB p50)in kidney tissues.Results Compared with the normal control group,the body mass of mice in the model control group was significantly lower after the second weeks of modeling(P＜0.05),and the levels of UA,Cr,UP,BUN,UUN,TNF-α,IL-6 contents and GLUT9 mRNA and κB p50 mRNA expression contents of kidney tissues were significantly higher(P＜0.01,P＜0.05).Compared with the model control group,the levels of Cr,UP,BUN and UUN contents and renal tissue nuclear cytokine κB p50 mRNA expression were significantly lower in the high,medium and low dose groups of Lithocarpus litseifoliu(P＜0.01,P＜0.05).The UA levels were significantly lower in the high dose group of Lithocarpus litseifoliu(P＜0.05),and renal ABCG2 mRNA expression was significantly higher in the medium dose group(P＜0.01).The renal URAT1 mRNA expression was significantly decreased in the low dose group(P＜0.01).Conclusion Lithocarpus litseifoliu has shown ameliorative effects on HN mice,and the mechanism may be related to the modulation of renal uric acid transporters,improvement of renal function and anti-inflammation effects.

Establishing a comprehensive mechanism for the initiation and review of investigator-initiated trial(IIT) plays an important role in ensuring the scientific validity of clinical research and improving research quality.Since 2021, Zhongshan Hospital affiliated to Fudan University had actively explored improvements in the project management of IIT. The hospital had established a standardized grading review management process, developed an integrated clinical research management system, established a three-level clinical research training system, built a methodological support platform, and formulated research plan templates, gradually formed a standardized grading project approval review management mode. As of February 2024, the hospital had completed 400 quick reviews and more than 400 expert letter reviews based on the integrated clinical research management system. The efficiency and quality of IIT project approval had been improved. At the same time, over 40 academic salons and forums had been held, cultivating a group of young clinical research talents, providing data management training for more than 30 clinical departments, and promoting the improvement of the quality of research protocol. In the future, hospitals should further optimize their information systems, expand the influence of their training systems, enhance the capabilities of their methodological support platforms, and improve the efficiency of the application of clinical research protocol templates, so as to escort the establishment and implementation of high-quality clinical research projects and provide references for other hospitals′ IIT project management.

Objective:Correct chest compression posture (CCP) is an important basis for high-quality cardiopulmonary resuscitation, but the research on CCP was still very limited. In this study, a new automatic analysis model was developed to achieve the purpose of objectification, standardization and automation of CCP monitoring.Methods:A total of 15 participants, including 11 professionals and 4 nonprofessionals, were recruited to participate in the field experiment. The video data were recorded simultaneously with zed cameras in the front and 45-degree sides. All participants performed 120 consecutive external chest compression operations on the Smartman CPR simulator. Three experts annotated the videos independently. An intelligent algorithm was used to extract human bone points for subsequent analysis and model development. The chi-square test was used to compare the rates of the professional and nonprofessional groups.Results:The results showed that problems with wrists, fingers, center of body weight and elbow bending had the highest incidence. Through 28 800 sets of standard human skeleton point coordinate data, we obtained a reasonable range of arm angles of 169.24°- 180.00° for the left arm and 168.49°-180.00° for the right arm. By the same method, the reasonable range of the center of gravity angle is 0.00°-18.46°. Based on these results, a new chest compression posture detection model based on a dual ZED camera was developed, which can accurately identify CCP errors (accuracy 91.31%; sensitivity 80.16%; specificity 93.53%).Conclusions:This study innovatively proposed an objective evaluation method for CCP. Moreover, a new chest compression posture detection model based on a dual ZED camera was developed, which can accurately identify CCP errors to achieve automation and standardization of quality control in CPR training.

Pulmonary fibrosis is a chronic， progressive and irreversible interstitial lung disease. At present， there is no specific drug for the treatment of pulmonary fibrosis， and many TCM monomers have potential therapeutic value for pulmonary fibrosis， among which flavonoids are the main representative. For example， total flavones of Astragalus memeranaceus and scutellarin can reduce inflammatory cell infiltration， lung injury and extracellular matrix （ECM） deposition by interfering with transforming growth factor-β1/drosophila MAD protein signaling pathway. Total flavonoids of Oxytropis falcata Bunge and salidroside can inhibit lung inflammation by mediating JAK/signal transduction and transcriptional activator signaling pathway， and prevent the epithelial interstitial transition （EMT） process. Quercetin and Ginkgo biloba leaf extract can reduce the apoptosis of macrophages by inhibiting the nuclear factor-κB signaling pathway and play an anti-pulmonary fibrosis role. Urushetin and proanthocyanidins can promote the morphological recovery of myofibroblasts and reduce ECM deposition through the phosphatidylinositol 3-kinase/protein kinase B/mammalian target protein of rapamycin signaling pathway. Naringin and luteolin can inhibit scorch death of macrophage and inflammation response， and improve lung function and lung tissue injury through NOD-like receptor heat protein domain related protein 3 signaling pathway. The ethanol extract of Phyllanthus emblica and calycosin can improve the inflammatory injury and fibrosis of lung tissue by activating the signaling pathway of nuclear transcription factor erythro2-related factor 2/antioxidant response element. Isogliquiritin can inhibit the phenotypic transformation of epithelial cells and reverse EMT progression by inhibiting extracellular signal-regulating kinase signaling pathway. In the future， scholars should consider developing appropriate drug carriers to improve their bioavailability and further study drug targets and pathways， to provide evidence for the development of traditional Chinese medicine monomers of flavonoids into clinical practice.

Objective:To investigate the mechanism by which chronic psychological stress aggravates intestinal barrier damage and promotes the development of enteritis through inhibiting Wnt/β-catenin pathway, so as to provide a new therapeutic strategy for the clinical diagnosis and treatment of inflammatory bowel disease (IBD).Methods:A comorbidity model of chronic psychological stress and enteritis was established using C57BL/6J mice. HE staining was used to analyze the effects of chronic psychological stress on the intestinal pathological damage in mice with enteritis. ELISA was used to detect the expression of proinflammatory cytokines. The ultrastructural changes of colonic cells and the state of intestinal mucus layer were observed under transmission electron microscope and scanning electron microscope. The secretion of mucoprotein 2 (MUC2) and the expression of cell proliferation marker Ki67 were detected by immunofluo rescence staining. The numbers of goblet cells were detected by Alcian blue-periodic acid-Schiff (AB-PAS) staining. Western blot was performed to analyze the expression of tight junction protein between intestinal epithelial cells, β-catenin which was a key protein of Wnt/β-catenin pathway maintaining crypt proliferation, and downstream protein c-myc.Results:The sugar water consumption ratio decreased, but tail suspension immobility time, the swimming immobility time and the expression of corticotropin releasing hormone (CRH) in hypothalamus increased (all P<0.05) in the stress group as compared with those in the control group. Chronic psychological stress promoted weight loss and colonic shortening in mice with enteritis, exacerbated pathological damage and enhanced the release of pro-inflammatory factors. Moreover, increased disappearance of intestinal epithelial microvilli and severe cellular ultrastructural damage were also observed in the stress+ dextran sulfate sodium salt (DSS) group. There was no pathological damage in the control and stress groups. Chronic psychological stress aggravated intestinal barrier injury and inhibited intestinal barrier repair by inhibiting Wnt/β-catenin pathway. Conclusions:In the mouse model of DSS-induced enteritis, chronic psychological stress preconditioning inhibited the Wnt/β-catenin pathway, weakened the repair ability of intestinal epithelium, aggravated the loss of mucus layer of intestinal barrier and the damage of tight junction structure, and promoted the development of enteritis. In the absence of enteritis, chronic psychological stress had no significant effects on the Wnt/β-catenin pathway and the intestinal barrier.

Dynasore is a small molecule that inhibits the GTPase activity of dynamin and mitochondria-related proteins both in vitro and in vivo,consequently preventing bacteria and viruses from entering cells via endocytic processes,impeding infection and spread of the pathogen.Dynasore is able to participate in cell survival,proliferation and apoptosis through a variety of dynamin protein-independent mechanisms such as reducing reactive oxygen species production,inhib-iting ferroptosis,lowering dynamin-related protein 1 activity to reduce mitophagy,and deeply engaging in vascular endo-thelial growth factor pathway.Here based on the molecular mechanisms and signaling pathways of dynasore involving in diseases,this review summarizes the role of dynasore in microbial infections,neurodegenerative diseases,and tumors.

In 2022,breast cancer ranks the first in incidence among all malignant tumors worldwide,and it's high recurrence and fatality rate has posed serious threat to human life and health.Triple negative breast cancer(TNBC)is known for its poor prognosis among all types of breast cancer,and is often associated with elevated expression of epidermal growth factor receptor(EGFR).EGFR is widely expressed on the surface of various cells.The signaling pathway mediated by EGFR is mainly involved in cell growth,proliferation and differentiation.EGFR overexpression is often closely related to tumor invasion,metastasis and prognosis.Therefore,elucidating the roles of EGFR in TNBC and developing prevention and treatment strategies correspondingly are helpful to prevent and control the occurrence of breast cancer,and improve patients'quality of life.This review summarizes the research progress in the roles of EGFR,the treatment strategies and drug resistance in TNBC,in order to provide more refence for treating and improving the prognosis of breast cancer.

Objective:To explore the role of digital three-dimensional printing technology and multifunctional occlusal splint in the treatment of mandibular fracture in children.Methods:From January 2006 to January 2022, 42 children with mandibular fracture were treated by Department of Stomatology, in The First Affiliated Hospital of Bengbu Medical College, including 25 males and 17 females. The patients, aged from 4 to 12 years, with the median age was 10 years old, were divided into observation group (22 cases) and routine group (20 cases) according to the treatment methods. In the observation group, the multifunctional occlusal splint was made before operation, and the CT data of the children were imported into Mimics software in".dicom"format, and the displaced mandible was virtually reset. The jaw reduction model was made by three-dimensional printing, and the surgical operation was simulated on the reduction model to determine the model and position of the internal fixation device and shape it. During the operation, the fracture was reduced and fixed according to the preoperative design. The conventional group was treated with open reduction and internal fixation of mandibular fracture by traditional methods, and the clinical application value was compared and analyzed through the intraoperative situation, occlusal relationship, and follow-up of the two groups.Results:The total intraoperative bleeding volume [(30.25±4.02) ml] and surgical time [(64.3±9.2) min] in the observation group were significantly lower than those in the conventional group [(35.13±5.69) ml and (84.6±13.9) min, respectively] ( F=6.18, P=0.003; F=1.32, P=0.001). The excellent and good rate of occlusal relationship in the observation group [96% (21/22)] was significantly higher than that in the conventional group [85% (17/20)] ( F=4.27, P=0.039). The incidence of complications, the observation group, 1 case of poor occlusion, 1 case of postoperative infection; In the routine group, there were 3 cases with poor occlusion, 1 case with nerve injury, 1 case with root injury and 1 case with tooth germ injury. Conclusions:The application of digitization three-dimensional printing technology combined with multifunctional occlusal splint in children′s mandibular fracture is minimally invasive, safe, efficient and accurate, and the clinical effect is good.