BACKGROUND:Socket-shield technique can effectively maintain labial soft and hard tissues,but the incidence of postoperative complications such as exposure and displacement of root shield is relatively high.It is speculated that the root shield may be exposed and displaced due to excessive load after long-term function of dental implants. OBJECTIVE:Through three-dimensional finite element analysis,we aim to study the influence of varying root shield thicknesses on the stress distribution,equivalent stress peaks,and displacement in the root shield,periodontal ligaments,implant,and surrounding alveolar bone under normal occlusal loading.We also attempt to analyze the correlation between the thickness of the root shield and occurrence of mechanical events such as root shield exposure,displacement,and fracture. METHODS:Cone-beam CT data of a patient who met the indication standard of socket-shield technique for maxillary central incisor were retrieved from database.Reverse engineering techniques were used to build models of the maxillary bone and root shield,while forward engineering was used to create models for the implant components based on their parameters.Models depicting various root shield thicknesses(0.5,1.0,1.5,and 2.0 mm)were created using Solidworks 2022 software.ANSYS Workbench 2021 software was then used to simulate and analyze the effects of varying root shield thicknesses on stress distribution,equivalent stress peaks,and displacement of the root shields,periodontal ligaments,implants,and surrounding alveolar bone under normal occlusion. RESULTS AND CONCLUSION:(1)In all root shield models,the stress was concentrated on the palatal cervical side,both sides of the edges and the lower edge of the labial side.As the thickness of the root shield increased,the equivalent stress peak and displacement showed a decreasing trend.The 0.5 mm thickness model produced a stress concentration of 176.20 MPa,which exceeded the yield strength(150 MPa)of tooth tissue.(2)The periodontal ligament stress in each group was concentrated in the neck margin and upper region.With the increase of root shield thickness,the equivalent stress peak and displacement of periodontal ligament showed a decreasing trend.(3)Implant stress in all models was concentrated in the neck of the implant and the joint of the implant-repair abutment,and the labial side was more concentrated than the palatal side.With the increase of root shield thickness,the equivalent stress peak of the implant in the model showed an increasing trend.(4)In each group of models,stress of cortical bone concentrated around the neck of the implant and the periphery of the root shield,and the labial side was more concentrated than the palatal side.With the increase of the thickness of the root shield,the equivalent stress peak around the root shield decreased;the peak value of the equivalent stress of the bone around the neck of the implant showed an increasing trend.In the model,the stress of cancellous bone was mainly concentrated around the neck of the lip of the implant,the top of the thread,the root tip and the lower margin of the root shield,and the labial side was more concentrated than the palatal side.With the increase of the thickness of the root shield,the peak value of the equivalent stress of the bone around the root shield in the model showed a decreasing trend.The minimum principal stress of cortical bone in each group of models was concentrated around the neck of the implant,exhibiting a fan-shaped distribution.As the thickness of the root shield increased,the minimum principal stress of cortical bone showed an increasing trend.(5)These results indicate that different thicknesses of the root shield have different biomechanical effects.The root shield with a thickness of 0.5 mm is easy to fracture.For patients with sufficient bone width,the root shield with a thickness of 2.0 mm is an option to reduce the risk of complications such as root shield exposure,fracture,and displacement.Meanwhile,it should be taken into account to protect the periodontal ligament in the preparation process,and rounding treatments ought to be carried out on both sides and the lower edge of the root shield.

To perform the phylogenetic characterization of an isolated porcine rotavirus(PoRV)and investigate its pathogenicity in suckling mice and piglets.A G4P[23]genotype PoRV strain JSJR2023 was successfully isolated from the diarrheic piglet feces through propagation in MA104 cells.The viral proliferation kinetics were analyzed using TCID50 assays,followed by complete genome sequencing through Sanger sequencing platforms.Comprehensive genotyping and phylogenetic reconstruction were conducted using MEGA7.0 with maximum likelihood algorithms.Pathogenicity was assessed in the following animal models:5-day-old C57BL/6 mice and 3-day-old piglets.Multidimensional evaluation included clinical monitoring(diarrhea scoring,growth parameters),virological detection,and histopathological analysis of intestinal tissues.The virus strain JSJR2023 could replicate efficiently in MA104 cells,achieving peak titers of 107.5 TCID50/mL.Whole genome genotype analysis showed that the strain belonged to G4-P[23]-I5-R1-C1-M1-A8-N1-T1-E1-H1.Phylogenetic analysis indicated that the VP3 and NSP4 genes of JSJR2023 strain were most closedrelated to human species rotaviruses,suggesting genetic reassortment between human and porcine RV strains.The animal experiments in suckling mice showed that the JSJR2023 strain infection caused diarrhea symptoms,intestinal edema and congestion,and shedding of intestinal villus epithelial cells.The pathogenicity experiments in piglets showed that compared with the control group,the challenged group of pig-lets had severe diarrhea symptoms,accompanied by reduced appetite and listlessness.Post-mortem examination revealed that the intes-tines were significantly thinner,congested,and filled with yellow watery contents.The challenged piglets showed typical pathological changes such as thinning of the intestinal wall and shortening and shedding of intestinal villi.In conclusion,this study successfully iso-lated a human-porcine recombinant G4P[23]PoRV strain and established the infection models in suckling mice and piglets,providing important tools for investigating the pathogenic mechanism of PoRV,evaluating vaccines and developing antiviral drug.

Non-human primate animal models are core tools for the study of highly pathogenic microorganisms and are irreplaceable in the fields of pathology and drug discovery.However,anatomical sampling of non-human primate infection models in high-level biosafety laboratories carries potential risk and related risk assessment and control measures require clarification.Based on biosafety regulations and practical experience,we systematically discuss the risk control strategies of anatomical operations with respect to personal protection,instrument selection,anatomical specifications,documentation,and personnel training.Our review will help to improve the management of high-level biosafety laboratories,reduce the risk of pathogen escape and human infection,and provide support for the safe research of highly pathogenic microorganisms.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

This study aims to evaluate the effects of sodium butyrate(NaBu)on preliminary follicle development of mice,using an in vitro 3D culture system.Preantral follicles were isolated from mouse ovaries(12.5 days post-birth)and cultured in vitro,NaBu was added for treatment during the culture process.Follicle morphology was observed and follicular diameter,survival rate,antral formation rate,oocyte maturation rate and early embryonic development were evaluated.The re-sults showed that an in vitro 3D culture system for preantral follicles of mice was successfully es-tablished.Matured follicles were cultured following an initial induction period of 8 days,after which M Ⅱ-stage oocytes were effectively expelled.During the process of follicle culture,the addition of varying doses(0.05-1.00 mmol/L)of NaBu from 0th day to 8 days had not showed any significant promotion in follicle development at any of the tested concentrations.NaBu at a dose of 0.10 mmol/L significantly increased antral formation rate(treated on 4th day for 2 days).In conclusion,short-term administration of appropriate doses of NaBu could significantly facilitate in vitro preantral follicle development and oocyte maturation by ensuring sustained developmental potential within follicles.This study may provide a theoretical basis for sodium butyrate to improve the reproduc-tive capacity of livestock and poultry in the breeding process.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

This study aims to evaluate the effects of sodium butyrate(NaBu)on preliminary follicle development of mice,using an in vitro 3D culture system.Preantral follicles were isolated from mouse ovaries(12.5 days post-birth)and cultured in vitro,NaBu was added for treatment during the culture process.Follicle morphology was observed and follicular diameter,survival rate,antral formation rate,oocyte maturation rate and early embryonic development were evaluated.The re-sults showed that an in vitro 3D culture system for preantral follicles of mice was successfully es-tablished.Matured follicles were cultured following an initial induction period of 8 days,after which M Ⅱ-stage oocytes were effectively expelled.During the process of follicle culture,the addition of varying doses(0.05-1.00 mmol/L)of NaBu from 0th day to 8 days had not showed any significant promotion in follicle development at any of the tested concentrations.NaBu at a dose of 0.10 mmol/L significantly increased antral formation rate(treated on 4th day for 2 days).In conclusion,short-term administration of appropriate doses of NaBu could significantly facilitate in vitro preantral follicle development and oocyte maturation by ensuring sustained developmental potential within follicles.This study may provide a theoretical basis for sodium butyrate to improve the reproduc-tive capacity of livestock and poultry in the breeding process.

Objective: To prepare hollow mesoporous silicon nanoparticles ( HMSNs) loaded with allicin—diallyl trisulfide (DATS) , and to study their feasibility as a therapeutic agent for ischemic injury of lower limbs . Methods: HMSNs were synthesized by selective etching , and their microstructure was observed by scanning and transmis- sion electron microscopy. Their physical and chemical properties were analyzed by X-ray diffraction and dynamic light scattering (DLS) . Their biological safety was tested by erythrocyte hemolysis and cytotoxicity experiments . DATS was loaded into HMSNs by adsorption to obtain DATS sustained release nanoparticles (DATS-HMSNs) , and the cumulative release curve of DATS was calculated and produced by ultraviolet spectrophotometry. C57BL/6 mice were randomly divided into four groups (sham operation group , normal saline group , DATS group , and DATS-HM- SNs group) . Lower limb ischemia models were made by femoral artery ligation and resection . The exercise ability and the contents of tumor necrosis factor alpha (TNF-α ) , interleukin-6 (IL-6) , monocyte chemoattractant protein- 1 (MCP-1) , reactive oxygen species (ROS) , platelet-endothelial cell adhesion molecule (CD31) , alpha smooth muscle actin ( α-SMA) , basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) in muscles of mice in each group before and after limb ischemia were tested . Results : Scanning and transmission e- lectron microscope observation showed that the prepared HMSNs were hollow , spherical and uniform in particle size . DLS results showed that the particle size was (226. 5 ± 11 . 8) nm. The results of red blood cell hemolysis test and cytotoxicity test showed that HMSNs had good biocompatibility. The maximum drug loading rate of HMSNs on DATS was 27. 89% , the cumulative release rate of DATS in 7 days was about 80. 12% , and could reach 97. 27% in 21 days . Compared with the control group , after DATS-HMSNs were applied to mice with lower limb ischemia , immunohistochemical staining showed that the levels of CD31 , α-SMA , bFGF and VEGF increased ( P < 0. 05) . Elisa test showed that the levels of TNF-α , IL-6 , MCP-1 and ROS decreased (P < 0. 05) , and the exercise ability of mice recovered satisfactorily after ischemia. Conclusion DATS-HMSNs can release DATS slowly and continu- ously , providing protection against ischemic injury of lower limbs .

Non-human primate animal models are core tools for the study of highly pathogenic microorganisms and are irreplaceable in the fields of pathology and drug discovery.However,anatomical sampling of non-human primate infection models in high-level biosafety laboratories carries potential risk and related risk assessment and control measures require clarification.Based on biosafety regulations and practical experience,we systematically discuss the risk control strategies of anatomical operations with respect to personal protection,instrument selection,anatomical specifications,documentation,and personnel training.Our review will help to improve the management of high-level biosafety laboratories,reduce the risk of pathogen escape and human infection,and provide support for the safe research of highly pathogenic microorganisms.

To perform the phylogenetic characterization of an isolated porcine rotavirus(PoRV)and investigate its pathogenicity in suckling mice and piglets.A G4P[23]genotype PoRV strain JSJR2023 was successfully isolated from the diarrheic piglet feces through propagation in MA104 cells.The viral proliferation kinetics were analyzed using TCID50 assays,followed by complete genome sequencing through Sanger sequencing platforms.Comprehensive genotyping and phylogenetic reconstruction were conducted using MEGA7.0 with maximum likelihood algorithms.Pathogenicity was assessed in the following animal models:5-day-old C57BL/6 mice and 3-day-old piglets.Multidimensional evaluation included clinical monitoring(diarrhea scoring,growth parameters),virological detection,and histopathological analysis of intestinal tissues.The virus strain JSJR2023 could replicate efficiently in MA104 cells,achieving peak titers of 107.5 TCID50/mL.Whole genome genotype analysis showed that the strain belonged to G4-P[23]-I5-R1-C1-M1-A8-N1-T1-E1-H1.Phylogenetic analysis indicated that the VP3 and NSP4 genes of JSJR2023 strain were most closedrelated to human species rotaviruses,suggesting genetic reassortment between human and porcine RV strains.The animal experiments in suckling mice showed that the JSJR2023 strain infection caused diarrhea symptoms,intestinal edema and congestion,and shedding of intestinal villus epithelial cells.The pathogenicity experiments in piglets showed that compared with the control group,the challenged group of pig-lets had severe diarrhea symptoms,accompanied by reduced appetite and listlessness.Post-mortem examination revealed that the intes-tines were significantly thinner,congested,and filled with yellow watery contents.The challenged piglets showed typical pathological changes such as thinning of the intestinal wall and shortening and shedding of intestinal villi.In conclusion,this study successfully iso-lated a human-porcine recombinant G4P[23]PoRV strain and established the infection models in suckling mice and piglets,providing important tools for investigating the pathogenic mechanism of PoRV,evaluating vaccines and developing antiviral drug.