Dental caries,a chronic disease characterized by tooth decay,occupies the second position in terms of disease burden and is primarily caused by cariogenic bacteria,especially Streptococcus mutans,because of its acidogenic,aciduric,and biofilm-forming capabilities.Developing novel targeted anti-virulence agents is always a focal point in caries control to overcome the limitations of conventional anti-virulence agents.The current study represents an up-to-date review of in silico approaches of drug design against dental caries,which have emerged more and more powerful complementary to biochemical attempts.Firstly,we categorize the in silico approaches into computer-aided drug design(CADD)and AI-assisted drug design(AIDD)and highlight the specific methods and models they contain respectively.Subsequently,we detail the design of anti-virulence drugs targeting single or multiple cariogenic virulence targets of S.mutans,such as glucosyltransferases(Gtfs),antigen Ⅰ/Ⅱ(AgⅠ/Ⅱ),sortase A(SrtA),the VicRK signal transduction system and superoxide dismutases(SODs).Finally,we outline the current opportunities and challenges encountered in this field to aid future endeavors and applications of CADD and AIDD in anti-virulence drug design.

Objective:To investigate the status of leisure crafting and post competence and their correlation among anesthesia specialist nurses.Methods:A convenience sampling method was used to conducted a questionnaire survey on 280 anesthesia specialist nurses at grade A tertiary hospitals in 19 provinces of China. Data were collected using a general information questionnaire, the Chinese version of Leisure Crafting Scale, and the Post Competency Scale for Anesthesia Specialist Nurses. SPSS 24.0 was used for t test and one-way analysis of variance. A Pearson correlation analysis was used to assess relationships between variables. Results:The total score of leisure crafting was (30.41±6.69) and the average score was (3.38±0.74). The total score of post competency was (141.76±21.76) and the average score was (3.73±0.57). A positive correlation was observed between leisure crafting and post competency ( r=0.215, P<0.01). Conclusions:Managers should encourage anesthesia specialist nurses to actively engage in leisure crafting and provide diverse opportunities for leisure crafting to improve their post competence and ultimately the quality of anesthesia nursing.

Objective To compare the medication rules of traditional Chinese medicine in the treatment of granulomatous lobular mastitis(GLM)and plasma cell mastitis(PCM).Methods The relevant literatures on GLM and PCM therapy published by CNKI,VIP,Wanfang Data Knowledge Service Platform and SinoMed from the establishment of the database to June 2024 were searched.The prescription was screened,and the frequency,nature and flavour,channel tropism were analyzed,and association rule analysis and cluster analysis were carried out.Results The top four most frequently used traditional Chinese medicines in the treatment of GLM and PCM were Chaihu,Pugongying,Zaojiaoci and Danggui.In the two-item association,the highest confidence levels for the treatment of the two were Huzhang→Muli and Ezhu→Sanleng.In the three-item association,the highest confidence levels for the treatment of the two were Huzhang→Jinyinhua-Pugongying and Chaihu→Yujin-Danggui.In the cluster analysis,the drugs for both could be clustered into four categories.Conclusion This study compares the medication rules of traditional Chinese medicine in the treatment of GLM and PCM,reflecting similarities and differences,and provides data reference for clinical compound research and development.

Dental caries, a chronic disease characterized by tooth decay, occupies the second position in terms of disease burden and is primarily caused by cariogenic bacteria, especially Streptococcus mutans, because of its acidogenic, aciduric, and biofilm-forming capabilities. Developing novel targeted anti-virulence agents is always a focal point in caries control to overcome the limitations of conventional anti-virulence agents. The current study represents an up-to-date review of in silico approaches of drug design against dental caries, which have emerged more and more powerful complementary to biochemical attempts. Firstly, we categorize the in silico approaches into computer-aided drug design (CADD) and AI-assisted drug design (AIDD) and highlight the specific methods and models they contain respectively. Subsequently, we detail the design of anti-virulence drugs targeting single or multiple cariogenic virulence targets of S. mutans, such as glucosyltransferases (Gtfs), antigen I/II (AgI/II), sortase A (SrtA), the VicRK signal transduction system and superoxide dismutases (SODs). Finally, we outline the current opportunities and challenges encountered in this field to aid future endeavors and applications of CADD and AIDD in anti-virulence drug design.

Objective:The composition and function of dental plaque biofilm are susceptible to alterations,potentially leading to vari-ous oral diseases.Although mesoporous bioactive glass(MBG)has been widely used,how it affects the microbial composition and bio-logical function of dental plaque biofilm remains unclear.This study aims to investigate the effects of MBG on the composition and bio-logical function of viable bacteria in dental plaque in vitro.Methods:At first,MBG was synthesized and characterized.Subsequently,the MBG was applied to dental plaque biofilm in vitro for a short term.The impact on biofilm biomass was assessed through colony-forming unit(CFU)counting.MBG-treated samples were collected for metatranscriptomic analyses of species composition and differen-tially expressed genes.Finally,reverse transcription quantitative polymerase chain reaction(RT-qPCR)was performed to validate the expression of core DEGs.Results:The results of CFU counting showed that short-term MBG treatment reduced dental plaque biofilm biomass in vitro by 44.25%.The results of metatranscriptomics showed that MBG significantly changed the species composition of den-tal plaque biofilm,where commensal Streptococci and Klebsiella were predominant.The function of carbohydrate metabolism was up-regulated,and the up-regulated genes were mainly enriched in the tricarboxylic acid(TCA)cycle.The results of RT-qPCR showed that a total of 9 genes associated with the TCA cycle were up-regulated.Conclusion:MBG can affect the species composition and enhance the carbohydrate metabolism of dental plaque biofilm in vi-tro,providing a new theoretical basis for the application of MBG in the oral field.

Objective:To investigate the status of leisure crafting and post competence and their correlation among anesthesia specialist nurses.Methods:A convenience sampling method was used to conducted a questionnaire survey on 280 anesthesia specialist nurses at grade A tertiary hospitals in 19 provinces of China. Data were collected using a general information questionnaire, the Chinese version of Leisure Crafting Scale, and the Post Competency Scale for Anesthesia Specialist Nurses. SPSS 24.0 was used for t test and one-way analysis of variance. A Pearson correlation analysis was used to assess relationships between variables. Results:The total score of leisure crafting was (30.41±6.69) and the average score was (3.38±0.74). The total score of post competency was (141.76±21.76) and the average score was (3.73±0.57). A positive correlation was observed between leisure crafting and post competency ( r=0.215, P<0.01). Conclusions:Managers should encourage anesthesia specialist nurses to actively engage in leisure crafting and provide diverse opportunities for leisure crafting to improve their post competence and ultimately the quality of anesthesia nursing.

Objective To compare the medication rules of traditional Chinese medicine in the treatment of granulomatous lobular mastitis(GLM)and plasma cell mastitis(PCM).Methods The relevant literatures on GLM and PCM therapy published by CNKI,VIP,Wanfang Data Knowledge Service Platform and SinoMed from the establishment of the database to June 2024 were searched.The prescription was screened,and the frequency,nature and flavour,channel tropism were analyzed,and association rule analysis and cluster analysis were carried out.Results The top four most frequently used traditional Chinese medicines in the treatment of GLM and PCM were Chaihu,Pugongying,Zaojiaoci and Danggui.In the two-item association,the highest confidence levels for the treatment of the two were Huzhang→Muli and Ezhu→Sanleng.In the three-item association,the highest confidence levels for the treatment of the two were Huzhang→Jinyinhua-Pugongying and Chaihu→Yujin-Danggui.In the cluster analysis,the drugs for both could be clustered into four categories.Conclusion This study compares the medication rules of traditional Chinese medicine in the treatment of GLM and PCM,reflecting similarities and differences,and provides data reference for clinical compound research and development.

Objective To investigate the effects of metformin(Met)on the proliferation of pancreatic cancer cells under different glucose concentration culture conditions,and to find the potential role of miR-139-5p in the process.Methods PANC-1 cells were treated with different concentrations of metformin(0/5/10/20 mmol/L)in 25 mmol/L(high-glucose group,HG)or 5 mmol/L(normal-glucose group,NG)glucose culture,cell proliferation,apoptosis,migration and cell cycle were detected after 48 h.The expression of miR-139-5p was quantitatively detected by RT-qPCR,and the miR-139-5p mimics were transfected into PANC-1 cells to clarify the role of miR-139-5p.Results Metformin inhibited the proliferation,promoted apoptosis,and induced S phase and G2/M phase arrest of PANC-1 cells under in high glucose and normal glucose culture conditions,and its anti-proliferation and pro-apoptosis effects were more significant in the normal glucose groups.The expression of miR-139-5p was up-regu-lated by metformin treatment in normal but not in high glucose culture.Further studies showed that miR-139-5p mimics inhibited of PANC-1 cells proliferation without metformin pre-incubation and enhanced the anti-prolifera-tion effect of 5 mmol/L metformin.The pro-apoptotic effect of 10 mmol/L metformin in normal glucose culture conditions.Conclusions In normal-glucose culture conditions,metformin can inhibit proliferation,induce apop-tosis and cell cycle arrest of PANC-1 cells more significantly than in higher-glucose culture,which may be partly related to the up-regulation of miR-139-5p.

Objective To determine the effect of enamel matrix derivative(EMD)on remineralization of artificial root dentin caries.Methods Bovine root dentin blocks were placed in a demineralization solution to create artificial root dentin carious lesions.The lesions were then randomly divided into EMD group(30 g/L EMD,the experimental group),sodium fluoride(NaF)aqueous solution group(1 g/L NaF,the positive control group)and distilled and deionised water(DDW)group(the negative control group),and all the lesions were pH-cycled at 6 cycles per day for 8 d.Morphology of the lesions were observed by scanning electron microscopy(SEM)and polarized light microscopy(PLM).Transverse microradiography(TMR)was used to examine mineral loss,lesion depth and mineral content.Results After pH-cycling,the surface morphology by SEM and the vertical morphology by PLM suggested that EMD and NaF treatment,but not DDW,caused mineral accumulation of artificial root dentin caries.Meanwhile,TMR revealed significantly lower mineral loss,shallower lesion depth and more mineral content in the EMD group than the DDW group(P＜0.05)after pH-cycling.Conclusion EMD can significantly promote remineralization of root dentin caries in vitro,and is a promising agent for non-invasive root caries therapy.

Objective To probe the spatial distribution of respiratory-related nuclei throughout the whole brain,and to investigate the circuit and projection links between the paraventricular hypothalamic nucleus (PVN)and the preB?tzinger complex (preB?tC)in mice.Methods Using a retrograde tracing strategy from peripheral to central,pseudorabies viruses (PRV)were microinjected into the diaphragm of mice to retrogradely label the upstream inputs brain regions from spinal respiratory phrenic motor neurons. The anterograde non-transsynaptic tracing viruses (AAV2/9-EGFP)were microinjected into the PVN to label the downstream brain region of the PVN;And using the Cre/loxP gene expression strategy,Dio-EGFP and Retro-Cre viruses were injected in the PVN and preB?tC,respectively,to validate the PVN-preB?tC circuit and the projection relationship between the two.Results The results of PRV-mediated retrograde tracing showed that PRV-EGFP-positive neurons were distributed in several brain regions such as PVN,preB?tC,nucleus tractus solitarii (NTS),locus coeruleus (LC)and periaqueductal grey (PAG).Except for the medulla oblongata region,the PVN brain region had the highest percentage of PRV-EGFP-positive neurons (P<0.0001 ).After AAV2/9-EGFP viruses were injected in the PVN,green neurofibrils were observed in the preB?tC brain region after viral infection;Dio-EGFP and Retro-Cre viruses were injected in the PVN and preB?tC,respectively,and green neuronal cells were seen in the brain region of the PVN after viral infection.Conclusion PVN is an important upstream input nucleus of spinal respiratory phrenic motor neurons,and has the potential to regulate respiration through direct projections from PVN-preB?tC circuit.