BACKGROUND:Erythropoietin has anti-inflammatory,anti-apoptotic,and pro-bone defect repair effects.To date,fewer studies have been conducted on its effects and molecular mechanism underlying restorative dentin formation after pulp injury. OBJECTIVE:To explore the effect of erythropoietin on restorative dentin formation after pulp injury. METHODS:(1)Animal experiment:Thirty-two rats were randomly divided into control group(n=16)and experimental group(n=16).In the experimental group,collagen sponges containing erythropoietin were used to directly cap the pulp at the pulp injury,and in the control group,collagen sponges containing PBS were used to directly cap the pulp at the exposed pulp injury.The cavity was then closed with glass ionomer adhesive.After 2 and 4 weeks of treatment,the maxillary bones of the two groups were collected,and the expression of nestin in dentin was detected by immunohistochemistry,and the reparative dentin production was observed by hematoxylin-eosin staining.The maxillae of four Sprague-Dawley rats were taken for immunohistochemical detection of erythropoietin expression in molar and incisor teeth.(2)Cell experiment:Human dental pulp cells,human periodontal ligament cells and human gingival fibroblasts were obtained from human dental tissue,periodontal ligament,and gingival tissue.Real-time reverse transcription PCR(RT-PCR)was used to detect the mRNA expression of erythropoietin.Erythropoietin,dentin sialophosphoprotein,dentin matrix protein 1,and nestin mRNA levels in human pulp cells were detected by RT-PCR under induced or uninduced odontoblastic differentiation.After down-regulation of erythropoietin expression or exogenous administration of erythropoietin intervention under induced or uninduced differentiation odontoblastic differentiation,the relative mRNA expression of dentin sialophosphoprotein and dentin matrix protein 1 in human pulp cells was detected by RT-PCR,and the formation of mineralized nodules was detected by alizarin red S staining,and mRNA and protein expressions of bone morphogenetic protein 2 were detected by RT-PCR and western blot,respectively. RESULTS AND CONCLUSION:(1)Animal experiment:Compared with the control group,the restorative dentin production and nestin expression were higher in the experimental group after 2 and 4 weeks of treatment.The expression of erythropoietin was weakly positive in pulp,odontoblastic cell layer and periodontal membrane of the rat's first maxillary molar,and strongly positive in odontoblasts.(2)Cell experiment:The mRNA expression of erythropoietin was higher in human dental pulp cells than in the other two types of cells.The mRNA expressions of dentin sialophosphorin,dentin matrix protein 1,nestin,erythropoietin and bone morphogenetic protein 2 in human pulp cells increased and the formation of mineralized nodules during odontoblastic differentiation under induction compared with non-induction conditions.The mRNA expression of dentin sialophosphoprotein,dentin matrix protein 1,nestin,bone morphogenetic protein 2 and the formation of mineralized nodules were decreased in human pulp cells after downregulation of erythropoietin under induced odontoblastic differentiation,and the protein expression of bone morphogenetic protein 2 was also decreased.After exogenous erythropoietin intervention,the expression of the above indexes in human dental pulp cells increased.To conclude,erythropoietin can promote the formation of dentin to some extent.

Adverse drug reactions (ADRs) significantly impact clinical medication safety. The timely identification and prediction of ADRs rely on the efficient analysis of real-world data, such as electronic health records, social media, and spontaneous reporting databases. In recent years, the rapid advancement of artificial intelligence, particularly large language models, in natural language processing, causal reasoning, and complex data mining has provided new technological means for real-time ADRs monitoring and individualized prediction. This paper summarizes the latest research achievements in AI-driven ADRs monitoring. Focusing on diverse data sources, including structured databases and electronic health records, it elaborates on the advantages andchallenges of AI in ADRs event extraction, relationship identification, causal analysis, and risk prediction. The aim is to provide a theoretical reference for constructing more intelligent and efficient ADRs monitoring systems.

Cisplatin resistance is an important factor in the poor treatment effect of ovarian cancer patients. MicroRNA (miRNA) can regulate cellular structural molecules, DNA repair, cell cycle, apoptosis and Wnt/β-catenin signaling pathway, autophagy, methylation and cancer stem cell, which are involved in the regulation of cisplatin resistance in ovarian cancer. Further understanding the mechanism of miRNA regulation of cisplatin resistance in ovarian cancer will help find new treatment options to optimize existing treatment plans and improve efficacy.

To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.

Objective:To investigate the influence of maternal autoimmune diseases and anticoagulants, including low-molecular-weight heparin (LMWH) and aspirin, on the fetal fraction of maternal plasma cell-free DNA of non-invasive prenatal testing (NIPT).Methods:A prospective cohort study was conducted on women with singleton pregnancies receiving NIPT in the Nanjing Drum Tower Hospital from March 2021 to July 2022. NIPT was carried out using a polymerase chain reaction (PCR)-free amplification platform. In this study, four types of maternal autoimmune diseases, which were antiphospholipid syndrome, undifferentiated connective tissue disease, Sj?gren's syndrome, and systemic lupus erythematosus (SLE), and two anticoagulants, LMWH and aspirin, were studied. Univariate and multivariate linear regression models were used to analyze the factors influencing fetal fraction of maternal plasma cell-free DNA.Results:A total of 4 102 singleton pregnant women were enrolled in the prospective cohort, and 3 948 were finally included after excluding the cases with unclear dosing time of LMWH or aspirin, other autoimmune diseases, conceiving through ovulation induction alone, and having true positive or failed NIPT result. There were 96 cases with antiphospholipid syndrome, 35 with undifferentiated connective tissue disease, 34 with Sj?gren's syndrome, and 18 with SLE. A total of 108 patients only received LMWH treatment, 121 only received aspirin treatment, and 113 received both LMWH and aspirin treatment. Univariate linear regression analysis showed that maternal body mass index at blood collection ( B=－0.423), conceived by assisted reproductive technology ( B=－0.803), male fetus ( B=－0.458), undifferentiated connective tissue disease ( B=1.774), and SLE ( B=3.467) had influence on the fetal fraction (all P<0.05). Multivariate linear regression analysis showed that maternal body mass index at blood collection ( B=－0.415), conceived by assisted reproductive technology ( B=－0.585), male fetus ( B=－0.322), SLE ( B=3.347) and undifferentiated connective tissue disease ( B=1.336) were factors influencing fetal fraction (all P<0.05). Conclusions:Maternal use of LMWH or aspirin does not affect fetal fraction when performing NIPT on a PCR-free amplification platform, but undifferentiated connective tissue disease and SLE are the influencing factors. Therefore, pregnant women should be informed before the NIPT that the fetal fraction of maternal plasma cell-free DNA may be affected by maternal autoimmune diseases.

Objective:This article aimed to explore and establish a systematic, progressive and standardized training content and path for ethics committee members, and also wants to continuously maintain and improve the quality and efficiency of ethical review, and at last wants to provide reference for the future formulation of ethics committee members training direction and system.Methods:This article analyzed the dilemma and the causes in the training process for ethics committee members through literature review, questionnaire survey, and policy researches, and at last focused on exploring the training content, timing, and methods.Results:We should begin with 3 dimensions: the ethics committee and its office, medical institutions, and higher government departments. We should also strengthen the training of ethics committee members through developing training plans, evaluating training effectiveness, improving training content, establishing training systems, reserving training teachers, leveraging the training functions of expert committees, promoting the construction of information exchange platforms, and strengthening international exchanges.Conclusions:It is imperative to strengthen training of ethics committee members, improve their competence, so as to improve the review quality of each ethics committee, and ultimately to safeguard the legitimate rights and interests of research participants.

Major depressive disorder(MDD)is a mental disease characterized by persistent depression,lack of interest and impaired cognitive function.Antidepressants currently availablein clinic are effective but accompanied by many adverse reactions,such as slow onset,cognitive impairment,sexual dysfunction.Therefore,novel antidepressant targets and therapeutic strategies with rapid onset of action,cognitive enhancement and low adverse effects have increasingly become a promising sphere of research.Studies have suggested that Sigma-1 receptor plays an important role in combating depression by regulating inflammatory response,excitation/inhibition balance and endoplasmic reticulum homeostasis.Moreover,Sigma-1 receptor agonists may have the advantages of rapid onset,enhanced cognition and low adverse reactions,which show good prospects for the development of new antidepressants.This article reviews the research progress related to Sigma 1 receptors in the regulatory mechanism and treatments for depression in the hopes of providing new insights into new antidepressants.

Due to the limitations of eruption time and space, third molars (M3s) are often impacted and induce a variety of oral diseases, bringing adverse effects on the health of their adjacent second molars (M2s). For a long time, a large number of studies have focused on the harm of impacted M3s (I-M3s) to the health of their adjacent teeth, while less attention has been paid to nonimpacted M3s (N-M3s) that have already erupted. In recent years, however, a growing number of studies and evidences have shown that the existence of N-M3s is also an important risk factor for various diseases of their adjacent teeth, whose hazard has not been taken seriously by dentists and patients. Based on the latest results of both domestic and international researches as well as our group, this review summarizes and explains the effects of N-M3s on the periodontal homeostasis and periodontal health of adjacent M2s, so as to provide reference for clinical decision-making of N-M3s and the healthy maintenance of their adjacent teeth.

Objective:To investigate the early recognition of coronary artery lesions(CAL)in Kawasaki disease(KD)and its relationship with monocyte/high-density lipoprotein cholesterol(HDL-C)ratio(MHR).Methods:A total of 216 children with KD who were hospitalized in Affiliated Hospital of Nantong University from June 2019 to June 2022 were selected as the research subjects,and divided into training set(162 cases)and test set(54 cases).The clinical data of the children were collected,and the children in the training set were divided into the CAL group(45 cases)and the NCAL group(117 cases)according to the diagnostic results of echo-cardiography,and the differences in clinical data and laboratory test results were compared between the two groups;Logistic regres-sion analysis was used to analyze the risk factors of CAL in children with KD;Pearson was used to analyze the correlation between MHR and CAL in children with KD.According to the MHR quantile,the children in the CAL group were divided into low MHR group(≤0.28),medium MHR group(0.29～0.42)and high MHR group(≥0.43),and they were analyzed and compared.Cox regression model was used to analyze the relationship between MHR and CAL risk in children with KD,and a predictive model was constructed based on the independent risk factors of CAL in children with KD.Results:There were 162 KD children with fever,and summer was a high incidence period;compared with the NCAL group,the CAL group had statistically significant differences in age,gender,fever time,KD type,MHR,WBC,PLT,NLR,and CRP(all P<0.05);Pearson correlation analysis showed that MHR was positively cor-related with the degree of coronary artery dilatation in children with CAL(r=0.743,P=0.001).and the risk of CAL in the KD children in the high MHR group was significantly higher than that in the low MHR group(HR=2.857,95%CI:1.329～6.431,P=0.003);Logis-tic regression analysis showed that gender,fever time,MHR,WBC,NLR and CRP were independent risk factors for CAL in children with KD.A prediction model was constructed based on the independent risk factors of CAL:Logit(P)=1.342+0.359×gender+0.181×ever time+1.064×MHR+0.459×WBC+0.146×NLR+0.211×CRP,P=e logit(P)/1+e logit(P),the AUC of this model was 0.874(95%CI:0.799～0.892),compared with the test set(AUC was 0.881,95%CI:0.785～0.913),the difference was not statistically sig-nificant(P>0.05);the AUC of MHR for predicting CAL in children with KD was 0.796,the sensitivity was 0.896,and the specificity was 0.824,which could be used as an early predictor of CAL in children with KD.Conclusion:MHR has a certain predictive value in the diagnosis of CAL in children with KD,and can reflect the degree of CAL in children with KD to a certain extent.Therefore,it is necessary to pay attention to the changes of MHR in children with KD in clinical practice.

Rapid turnover of the intestinal epithelium is a critical strategy to balance the uptake of nutrients and defend against environmental insults, whereas inappropriate death promotes the spread of inflammation. PPARα is highly expressed in the small intestine and regulates the absorption of dietary lipids. However, as a key mediator of inflammation, the impact of intestinal PPARα signaling on cell death pathways is unknown. Here, we show that Pparα deficiency of intestinal epithelium up-regulates necroptosis signals, disrupts the gut vascular barrier, and promotes LPS translocation into the liver. Intestinal Pparα deficiency drives age-related hepatic steatosis and aggravates hepatic fibrosis induced by a high-fat plus high-sucrose diet (HFHS). PPARα levels correlate with TRIM38 and MLKL in the human ileum. Inhibition of PPARα up-regulates necroptosis signals in the intestinal organoids triggered by TNF-α and LPS stimuli via TRIM38/TRIF and CREB3L3/MLKL pathways. Butyric acid ameliorates hepatic steatosis induced by intestinal Pparα deficiency through the inhibition of necroptosis. Our data suggest that intestinal PPARα is essential for the maintenance of microenvironmental homeostasis and the spread of inflammation via the gut-liver axis.