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.

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.

Estrogen, through binding to its receptors in the female endometrium, promotes the proliferation, differentiation, and angiogenesis of endometrial stromal cells, thereby playing a critical role in endometrial injury repair, regeneration, and the prevention and treatment of intrauterine adhesions. Currently, various estrogen-based pharmaceutical formulations are applied in clinical practice, and the development of related products is progressively advancing. This review systematically outlines the etiology of endometrial injury and the mechanisms by which estrogen facilitates endometrial repair and regeneration. Furthermore, it highlights recent research progress and clinical applications of estrogen-based therapies in endometrial regeneration, aiming to provide a valuable reference for relevant scientific research and clinical practice.

Estrogen, through binding to its receptors in the female endometrium, promotes the proliferation, differentiation, and angiogenesis of endometrial stromal cells, thereby playing a critical role in endometrial injury repair, regeneration, and the prevention and treatment of intrauterine adhesions. Currently, various estrogen-based pharmaceutical formulations are applied in clinical practice, and the development of related products is progressively advancing. This review systematically outlines the etiology of endometrial injury and the mechanisms by which estrogen facilitates endometrial repair and regeneration. Furthermore, it highlights recent research progress and clinical applications of estrogen-based therapies in endometrial regeneration, aiming to provide a valuable reference for relevant scientific research and clinical practice.

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 investigate the enhanced CT and MRI imaging features of nasal sinus squamous cell carcinoma(SCC)and lymphoma(NHL),and to analyze the efficacy of different imaging features in differentiating nasal sinus SCC from NHL.Methods The imaging,clinical and pathological data of 67 patients with sinus SCC and NHL who underwent sinus CT and MRI with contrast CT and MRI in our hospital and confirmed by surgical pathology were retrospectively analyzed,and the tumor origin,maximum diameter,CT density,MRI signal intensity,enhancement degree,tumor internal necrosis,adjacent bone destruction,invasion of surrounding tissues,and The imaging features such as cervical lymph node metastasis within the scanning range were analyzed,and the receiver operating characteristic(ROC)curve and area under the curve(AUC)were used to analyze the efficacy of different imaging features to distinguish nasal sinus SCC and NHL.Results There were statistically significant differences between the five imaging features of nasal sinus SCC and NHL,including tumor origin,maximum diameter,internal tumor necrosis,surrounding bone destruction and peripheral tissue invasion(P＜0.05),and the AUC of differentiating SCC and NHL were 0.708,0.694,0.785,0.850 and 0.629,respectively.The AUC of SCC and NHL was 0.969,and the sensitivity and specificity were 83.9%and 97.2%,respectively.Conclusion On contrast-enhanced CT and MRI,the imaging signs of tumor origin,maximum diameter,tumor internal necrosis,bone destruction and surrounding tissue invasion are helpful to distinguish nasal sinus SCC from NHL,especially if the tumor originates in the nasal cavity,necrosis is rare,bone destruction is mild,and the possibility of nasal sinus NHL should be given priority.Contrast-enhanced CT and MRI can help differentiate nasal sinus SCC from NHL,and the combination can help improve differential diagnostic performance.

Objective:To establish a high-performance liquid chromatography (HPLC) for determining the content of levonorgestrel (LNG) and ethinylestradiol (EE) in compound levonorgestrel sustained-release microsphere injection.Methods:C18 column Inertsil ODS-3 (4.7 mm×250 mm, 5 μm) was used. The mobile phase was acetonitrile-water (50∶50, V/V). The flow rate was 1.0 mL/min. The column temperature was 35 ℃. The detection wavelength was 265 nm, and the injection amount was 20 μL. The content of microspheres was determined after validation of HPLC detection methodology.Results:The linear relationship was good in the range of 5.03-201.20 μg/mL LNG, 1.55-61.92 μg/mL EE ( r2=0.999 8). The specificity, precision, recovery, repeatability, stability, etc, met the requirements. The content of LNG in the compound LNG sustained-release microspheres injection was 16.26%, and the content of EE was 2.58%. Conclusion:This HPLC can determine the content of compound levonorgestrel sustained-release injection microspheres, and the method is simple, stable, and has good reproducibility, providing a reference for the determination of levonorgestrel and ethinylestradiol in compound sustained-release preparations.

Objective:To establish a high-performance liquid chromatography (HPLC) for determining the content of levonorgestrel (LNG) and ethinylestradiol (EE) in compound levonorgestrel sustained-release microsphere injection.Methods:C18 column Inertsil ODS-3 (4.7 mm×250 mm, 5 μm) was used. The mobile phase was acetonitrile-water (50∶50, V/V). The flow rate was 1.0 mL/min. The column temperature was 35 ℃. The detection wavelength was 265 nm, and the injection amount was 20 μL. The content of microspheres was determined after validation of HPLC detection methodology.Results:The linear relationship was good in the range of 5.03-201.20 μg/mL LNG, 1.55-61.92 μg/mL EE ( r2=0.999 8). The specificity, precision, recovery, repeatability, stability, etc, met the requirements. The content of LNG in the compound LNG sustained-release microspheres injection was 16.26%, and the content of EE was 2.58%. Conclusion:This HPLC can determine the content of compound levonorgestrel sustained-release injection microspheres, and the method is simple, stable, and has good reproducibility, providing a reference for the determination of levonorgestrel and ethinylestradiol in compound sustained-release preparations.

Objective:To observe the effect of large pushing Tianheshui manipulation intervention on the body temperature of young rabbits with endotoxin-induced fever and discuss its antipyretic mechanism.Methods:Thirty-two young rabbits meeting the standards were selected from 40 ordinary young male New Zealand rabbits after being adapted for 7 d,and randomly divided into a normal group,a model group,a large pushing Tianheshui group,and an ibuprofen group according to the random number table method,with 8 rabbits in each group.Rabbits in the model group,the large pushing Tianheshui group,and the ibuprofen group were subjected to preparing the endotoxin-induced fever model by intravenous lipopolysaccharide from the marginal ear vein.Rabbits in the large pushing Tianheshui group received Tuina(Chinese therapeutic massage)manipulation intervention 1.5 h and 2.5 h after modeling,respectively.Rabbits in the ibuprofen group were intragastrically given ibuprofen suspension 1.5 h after modeling.The dynamic changes in body temperature were observed for the young rabbits after fever modeling.Enzyme-linked immunosorbent assay was used to determine the content changes in positive mediators of hypothalamic body temperature,including prostaglandin(PG)E2 and cyclic adenosine monophosphate(cAMP),as well as negative mediators of hypothalamic body temperature,including arginine vasopressin(AVP)and α-melanocyte stimulating hormone(α-MSH).Results:The body temperature of the young rabbits in the model group was significantly higher than that in the normal group at 0.5-4.0 h,5.0 h,and 5.5 h after modeling(P＜0.01),showing two obvious fever peaks in the model group at 1.5 h and 3.0 h after modeling,respectively,with the highest peak at 1.5 h.Compared with the model group,body temperatures of the large pushing Tianheshui group and the ibuprofen group decreased significantly after 0.5 h of intervention(P＜0.05).Compared with the normal group,the contents of PGE2 and cAMP were significantly increased(P＜0.05),and the contents of AVP and α-MSH were significantly decreased(P＜0.01)in the hypothalamus of the model group.Compared with the model group,the contents of PGE2 and cAMP were significantly decreased(P＜0.01),and the levels of AVP and α-MSH were significantly increased(P＜0.01)in the hypothalamus in the large pushing Tianheshui group and the ibuprofen group.There were no significant differences in the PGE2,cAMP,AVP,and α-MSH contents in the hypothalamus between the ibuprofen group and the large pushing Tianheshui group(P＞0.05).Conclusion:Large pushing Tianheshui manipulation has a significant antipyretic effect on endotoxin-induced fever in young rabbits.The mechanism may be related to inhibiting the positive regulators(PGE2 and cAMP)and promoting the negative regulators(AVP and α-MSH)of hypothalamic control of body temperature.