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.

Clinicians need to focus on various points in the diagnosis and treatment of insomnia.This article prescribed the treatment protocol based on the unique features,such as insomnia in the elderly,women experiencing specific physiologi-cal periods,children insomnia,insomnia in sleep-breathing disorder patients,insomnia in patients with chronic liver and kidney dysfunction.It pro-vides some reference for clinicians while they make decision on diagnosis,differentiation and treat-ment methods.

Immune evasion has made ovarian cancer notorious for its refractory features, making the development of immunotherapy highly appealing to ovarian cancer treatment. The immune-stimulating cytokine IL-12 exhibits excellent antitumor activities. However, IL-12 can induce IFN-γ release and subsequently upregulate PDL-1 expression on tumor cells. Therefore, the tumor-targeting folate-modified delivery system F-DPC is constructed for concurrent delivery of IL-12 encoding gene and small molecular PDL-1 inhibitor (iPDL-1) to reduce immune escape and boost anti-tumor immunity. The physicochemical characteristics, gene transfection efficiency of the F-DPC nanoparticles in ovarian cancer cells are analyzed. The immune-modulation effects of combination therapy on different immune cells are also studied. Results show that compared with non-folate-modified vector, folate-modified F-DPC can improve the targeting of ovarian cancer and enhance the transfection efficiency of pIL-12. The underlying anti-tumor mechanisms include the regulation of T cells proliferation and activation, NK activation, macrophage polarization and DC maturation. The F-DPC/pIL-12/iPDL-1 complexes have shown outstanding antitumor effects and low toxicity in peritoneal model of ovarian cancer in mice. Taken together, our work provides new insights into ovarian cancer immunotherapy. Novel F-DPC/pIL-12/iPDL-1 complexes are revealed to exert prominent anti-tumor effect by modulating tumor immune microenvironment and preventing immune escape and might be a promising treatment option for ovarian cancer treatment.

ObjectiveTo establish a dose-effect curve for semi-automatic analysis of dicentric chromosomes(DC) based on an automatic chromosome analysis system. Methods A total of three healthy volunteers were recruited as the study subjects, and their peripheral blood was collected and stimulated by X-ray at doses of 0.00, 0.10, 0.25, 0.50, 0.75, 1.00, 2.00, 3.00, 4.00, and 5.00 Gy, with the absorbed dose rate of 1.0 Gy/min. Images of DC in the mid-stage of cell division were collected using a high-throughput automatic chromosome analysis system. The DCScore software was used to automatically analyze DC aberrations, and a dose-effect curve for semi-automatic analysis of DC was fitted after manual confirmation. The fitted dose-effect curve for semi-automatic analysis of DC was validated for accuracy using three proficiency test samples from the national quality assessment of biological dose. Results The incidence of DC increased with increasing irradiation doses in the range of 0.00-5.00 Gy (P<0.01). The dose-effect curve for the fitted semi-automatic analysis of DC was ŷ =0.000 8 (±0.000 2) +0.009 2(±0.000 9) D+0.014 2(±0.000 4) D² (R²= 0.999 8). The relative deviation between the estimated dose and the actual dose of the three test samples was about 20.00%, indicating curve applicability for biological dose estimation. Moreover, excluding the time spent on manual analysis, the semi-automatic analysis method increased the analysis efficiency by 26.0 times. Conclusion The semi-automatic analysis dose-effect curve for DC stimulated by X-ray is constructed for biological dose estimation, which can reduce the manual analysis time, and holds great potential for application in nuclear emergency response to large-scale radiation accidents.

BACKGROUND:With the increasing number of tendon transplantation surgeries for tendon injuries,the demand for tendon tissue engineering scaffolds is increasing.Research has found that good pore size and porosity of implants contribute to tissue healing. OBJECTIVE:To review the types of materials currently published for tendon tissue engineering scaffolds and investigate the correlation between various tendon tissue engineering scaffold materials and pores. METHODS:Articles were retrieved on PubMed,Embase,and Web of Science databases,using keywords"tendon"or"ligament"and"tissue scaffold"as well as"porosity"or"permeability".A total of 84 articles meeting the criteria were included to summarize,discuss and anticipate future development directions. RESULTS AND CONCLUSION:The materials used in the research of tendon tissue engineering are mainly divided into two categories:natural tendon scaffold materials and artificial synthetic tendon scaffold materials.Natural scaffold materials include autologous tendons,allogeneic tendons,and xenogeneic tendons.Autogenous tendons and allogeneic tendons have been used in clinical practice for many years.During the preparation of allogeneic tendons and animal experiments,it was found that the process of acellular disinfection resulted in an increase in the pore size and porosity of both types of tendons,but the specific reasons and mechanisms have not been further studied.There are many types of artificial tendon scaffold materials currently being studied,among which artificial ligament products such as Leeds Keio and LARS(Ligament Advanced Reinforcement System)are still in use in some countries.Other materials have not been promoted in clinical practice due to immature technology and other issues.The pores and porosity of artificial tendon scaffold materials also show different trends due to their different materials and preparation techniques.

Objective To explore the effect of long non-coding RNA (lncRNA) NUTM2A-AS1 on the damage of vascular endothelial cells induced by oxidized low density lipoprotein (oxLDL) and its molecular mechanism. Methods Human umbilical vein endothelial cells(HUVECs) were cultured in DMEM medium. The HUVECs treated with 100 μg/mL oxLDL were assigned to oxLDL group, while those cultured under normal conditions were assigned to Con group. After transfection of the lncRNA NUTM2A-AS1 interference expression vector and negative control, microRNA-129-5p mimic and negative control into HUVECs, the cells treated with 100 μg/mL oxLDL were assigned to oxLDL+si-NUTM2A-AS1 group, oxLDL+si-NC group, oxLDL+miR-129-5p group, and oxLDL+miR-NC group, respectively. After co-transfection of the lncRNA NUTM2A-AS1 interference expression vector and miR-129-5p inhibitor or negative control into HUVECs, the cells treated with 100 μg/mL oxLDL were assigned to oxLDL+si-NUTM2A-AS1+anti-miR-129-5p group and oxLDL+si-NUTM2A-AS1+anti-miR-NC group. The levels of malondialdehyde (MDA) in cells, as well as the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured using kits. Cell apoptosis was detected by flow cytometry. Protein expression was detected by Western blot. The targeting relationship between NUTM2A-AS1 and miR-129-5p was detected by dual luciferase reporter assay and RNA pull-down experiments. Results Compared with the Con group, the expression level of lncRNA NUTM2A-AS1 was increased, the expression level of miR-129-5p was decreased, the content of MDA was increased, the activities of SOD and GSH-Px were decreased, the apoptosis rate of vascular endothelial cells and the expression levels of cleaved-caspase3 and cleaved-caspase9 were increased in the oxLDL group (P < 0.05). After interference of lncRNA NUTM2A-AS1 expression or overexpression of miR-129-5p, the content of MDA was decreased, the activities of SOD and GSH-Px were increased, cell apoptosis was reduced (P < 0.05). The damage to vascular endothelial cells mediated by knockdown of lncRNA NUTM2A-AS1 under oxLDL conditions can be reversed by downregulation of miR-129-5p. LncRNA NUTM2A-AS1 targeted miR-129-5p for regulation. Conclusion Interference of lncRNA NUTM2A-AS1 expression can inhibit oxLDL-induced vascular endothelial cell damage by targeting miR-129-5p for upregulation.

Objective:To analyze the level of chromosome aberration in lymphocytes of medical radiation workers and its influencing factors.Methods:From July to September 2020, 252 medical workers in a tertiary hospital were selected as the study subjects and 107 preserviceworkers were selected as the control group. The Chromosomal aberrations of peripheral blood lymphocytes were measured using conventional cytogenetic analysis method, and the differences were analyzed.Results:The frequencies of dicentric puls centric ring, total chromosome-type aberrations, and abnormal detection rate in the radiation group were significantly higher than those in the control group ( Z=2.59, 3.74, 9.99, P<0.05). There was significant difference in the frequencies of dicentric plus centric ring and total chromosome-type aberrations among different types of work (χ 2=8.59, 8.17, 11.39, P<0.05), and the frequencies of dicentric plus centric ring were significantly higher in the interventional radiology group than those in diagnostic radiology (χ 2=2.90, P<0.05), While the rates of acentric fragment and total chromosome-type aberrations were significantly higher in the nuclear medicine group than those in diagnostic radiology (χ 2=2.81, 3.19, P<0.05). The difference in the abnormal detection rate of chromosome aberrations between different types of work was statistically significant ( P<0.05), and the rate in the interventional radiology group was significantly higher than that in the diagnostic radiology group (χ 2=7.66, P<0.05). There was no significant difference in chromosome aberration level and abnormal detection rate among different working ages ( P>0.05). Poisson regression analysis indicated that the type of work is a risk factor for chromosomal aberration [ IRR=2.31 (nuclear medicine group), 1.66 (Radiation therapy), and 1.78 (interventional group) ; P<0.05]. Conclusion:Ionizing radiation causes certain radiation damage to medical radiology workers, and the frequencies of chromosome aberration in the radiation workers of nuclear medicine and interventional radiology groups are relatively high, so radiation protection should be strengthened to ensure the health of relevant workers.

Objective To investigate the levels of N-terminal probrain natriuretic peptide(NT-proBNP),thrombolomodulin(TM),C-type lectin-like receptor 2(CLEC-2),galectin-3(Gal-3)and their relationships with prognosis in patients with acute coronary syndrome(ACS)after percuta-neous coronary intervention(PCI).Methods A total of 80 patients with ACS were selected as study objects.The patients were followed up for 6 months by outpatient visit or telephone follow-up,and the occurrence of major adverse cardiovascular events(MACE)was recorded in the patients.According to the occurrence of MACE,patients were divided into MACE group(26 cases)and control group(54 cases).The changes of serological indexes were compared between the two groups.Results The expression levels of NT-proBNP,CLEC-2,TM and Gal-3 in serum of patients in the MACE group were significantly higher than those of control group(P＜0.05).Multivariate Logistic regression analysis showed that NT-proBNP,CLEC-2,TM,and Gal-3 were all influential factors for the occur-rence of MACE after PCI in ACS patients(P＜0.05).Conclusion NT-proBNP,CLEC-2,TM and Gal-3 are influencing factors for MACE in patients with ACS after PCI,and have a good predictive role in evaluating the occurrence of MACE.

Objective To investigate the levels of N-terminal probrain natriuretic peptide(NT-proBNP),thrombolomodulin(TM),C-type lectin-like receptor 2(CLEC-2),galectin-3(Gal-3)and their relationships with prognosis in patients with acute coronary syndrome(ACS)after percuta-neous coronary intervention(PCI).Methods A total of 80 patients with ACS were selected as study objects.The patients were followed up for 6 months by outpatient visit or telephone follow-up,and the occurrence of major adverse cardiovascular events(MACE)was recorded in the patients.According to the occurrence of MACE,patients were divided into MACE group(26 cases)and control group(54 cases).The changes of serological indexes were compared between the two groups.Results The expression levels of NT-proBNP,CLEC-2,TM and Gal-3 in serum of patients in the MACE group were significantly higher than those of control group(P＜0.05).Multivariate Logistic regression analysis showed that NT-proBNP,CLEC-2,TM,and Gal-3 were all influential factors for the occur-rence of MACE after PCI in ACS patients(P＜0.05).Conclusion NT-proBNP,CLEC-2,TM and Gal-3 are influencing factors for MACE in patients with ACS after PCI,and have a good predictive role in evaluating the occurrence of MACE.

Objective:To analyze the level of chromosome aberration in lymphocytes of medical radiation workers and its influencing factors.Methods:From July to September 2020, 252 medical workers in a tertiary hospital were selected as the study subjects and 107 preserviceworkers were selected as the control group. The Chromosomal aberrations of peripheral blood lymphocytes were measured using conventional cytogenetic analysis method, and the differences were analyzed.Results:The frequencies of dicentric puls centric ring, total chromosome-type aberrations, and abnormal detection rate in the radiation group were significantly higher than those in the control group ( Z=2.59, 3.74, 9.99, P<0.05). There was significant difference in the frequencies of dicentric plus centric ring and total chromosome-type aberrations among different types of work (χ 2=8.59, 8.17, 11.39, P<0.05), and the frequencies of dicentric plus centric ring were significantly higher in the interventional radiology group than those in diagnostic radiology (χ 2=2.90, P<0.05), While the rates of acentric fragment and total chromosome-type aberrations were significantly higher in the nuclear medicine group than those in diagnostic radiology (χ 2=2.81, 3.19, P<0.05). The difference in the abnormal detection rate of chromosome aberrations between different types of work was statistically significant ( P<0.05), and the rate in the interventional radiology group was significantly higher than that in the diagnostic radiology group (χ 2=7.66, P<0.05). There was no significant difference in chromosome aberration level and abnormal detection rate among different working ages ( P>0.05). Poisson regression analysis indicated that the type of work is a risk factor for chromosomal aberration [ IRR=2.31 (nuclear medicine group), 1.66 (Radiation therapy), and 1.78 (interventional group) ; P<0.05]. Conclusion:Ionizing radiation causes certain radiation damage to medical radiology workers, and the frequencies of chromosome aberration in the radiation workers of nuclear medicine and interventional radiology groups are relatively high, so radiation protection should be strengthened to ensure the health of relevant workers.