Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling.Here,we focused on the role of Semaphorin 3A(Sema3A),expressed by sensory nerves,in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM)model.Firstly,bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold.Sema3A,rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM.Moreover,in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs)within 24 hours.Furthermore,exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload.Mechanistically,Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway,maintaining mitochondrial dynamics as mitochondrial fusion.Therefore,Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation,both as a pain-sensitive analgesic and a positive regulator for bone formation.

Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling.Here,we focused on the role of Semaphorin 3A(Sema3A),expressed by sensory nerves,in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM)model.Firstly,bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold.Sema3A,rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM.Moreover,in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs)within 24 hours.Furthermore,exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload.Mechanistically,Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway,maintaining mitochondrial dynamics as mitochondrial fusion.Therefore,Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation,both as a pain-sensitive analgesic and a positive regulator for bone formation.

Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling.Here,we focused on the role of Semaphorin 3A(Sema3A),expressed by sensory nerves,in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM)model.Firstly,bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold.Sema3A,rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM.Moreover,in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs)within 24 hours.Furthermore,exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload.Mechanistically,Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway,maintaining mitochondrial dynamics as mitochondrial fusion.Therefore,Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation,both as a pain-sensitive analgesic and a positive regulator for bone formation.

Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling.Here,we focused on the role of Semaphorin 3A(Sema3A),expressed by sensory nerves,in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM)model.Firstly,bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold.Sema3A,rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM.Moreover,in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs)within 24 hours.Furthermore,exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload.Mechanistically,Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway,maintaining mitochondrial dynamics as mitochondrial fusion.Therefore,Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation,both as a pain-sensitive analgesic and a positive regulator for bone formation.

Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling.Here,we focused on the role of Semaphorin 3A(Sema3A),expressed by sensory nerves,in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM)model.Firstly,bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold.Sema3A,rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM.Moreover,in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs)within 24 hours.Furthermore,exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload.Mechanistically,Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway,maintaining mitochondrial dynamics as mitochondrial fusion.Therefore,Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation,both as a pain-sensitive analgesic and a positive regulator for bone formation.

Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling.Here,we focused on the role of Semaphorin 3A(Sema3A),expressed by sensory nerves,in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM)model.Firstly,bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold.Sema3A,rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM.Moreover,in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs)within 24 hours.Furthermore,exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload.Mechanistically,Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway,maintaining mitochondrial dynamics as mitochondrial fusion.Therefore,Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation,both as a pain-sensitive analgesic and a positive regulator for bone formation.

Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling.Here,we focused on the role of Semaphorin 3A(Sema3A),expressed by sensory nerves,in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM)model.Firstly,bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold.Sema3A,rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM.Moreover,in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs)within 24 hours.Furthermore,exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload.Mechanistically,Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway,maintaining mitochondrial dynamics as mitochondrial fusion.Therefore,Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation,both as a pain-sensitive analgesic and a positive regulator for bone formation.

Bone formation and deposition are initiated by sensory nerve infiltration in adaptive bone remodeling.Here,we focused on the role of Semaphorin 3A(Sema3A),expressed by sensory nerves,in mechanical loads-induced bone formation and nerve withdrawal using orthodontic tooth movement(OTM)model.Firstly,bone formation was activated after the 3rd day of OTM,coinciding with a decrease in sensory nerves and an increase in pain threshold.Sema3A,rather than nerve growth factor(NGF),highly expressed in both trigeminal ganglion and the axons of periodontal ligament following the 3rd day of OTM.Moreover,in vitro mechanical loads upregulated Sema3A in neurons instead of in human periodontal ligament cells(hPDLCs)within 24 hours.Furthermore,exogenous Sema3A restored the suppressed alveolar bone formation and the osteogenic differentiation of hPDLCs induced by mechanical overload.Mechanistically,Sema3A prevented overstretching of F-actin induced by mechanical overload through ROCK2 pathway,maintaining mitochondrial dynamics as mitochondrial fusion.Therefore,Sema3A exhibits dual therapeutic effects in mechanical loads-induced bone formation,both as a pain-sensitive analgesic and a positive regulator for bone formation.

Objective·To reveal the direction,efficiency,and mechanical load of single tooth displacement with clear aligners for expansion treatment during the transitional dentition period with the aid of finite element analysis.Additionally,overcorrection and torque compensation systems were designed to address insufficient expansion efficiency and buccal inclination of posterior teeth.Methods·One volunteer in mixed dentition period was included to construct a three dimentional cranio-maxillary complex model and an invisible orthodontic system,simulating the buccal displacement(load 1?4:0.200,0.275,0.300,0.325 mm,respectively)and root buccal torque(load 1:buccal displacement load 0.200 mm,root buccal torque 0°;load 5:buccal displacement load 0.275 mm,root buccal torque 1.0°;load 6:buccal displacement load 0.300 mm,root buccal torque 1.3° and load 7:buccal displacement load 0.325mm,root buccal torque 1.8°)on the maxillary deciduous teeth to the first permanent molar with a non bracket invisible orthodontic appliance.Through finite element analysis,the tooth displacement and equivalent stress distribution of the periodontal membrane can be calculated.Results·Expansion treatment with clear aligners in the transitional dentition phase primarily revealed the effect of buccal expansion of teeth;different teeth achieved different levels of expansion rate.At a set expansion amount of 0.200 mm per side,expansion efficiency in the maxillary first permanent molar was 51.86%,second primary molar 68.76%,first primary molar 73.48%,and primary cuspid 84.17%.By designing over-correction(0.275,0.300,0.325 mm),the results showed significant enhancement in expansion effect.When overcorrection length reached 150%(0.300 mm),expansion efficiency at the maxillary first permanent molar,second primary molar,first primary molar,and primary cuspid were 75.16%,99.96%,107.35%,and 122.37%,respectively.The expansion efficiency of maxillary second primary molar,first primary molar,and primary cuspid was close to 100.00%.The overcorrection design exacerbated the dental effects of expansion,intensifying the tendency for teeth to tilt toward the cheek side,leading to side effects such as buccal inclination and drooping of the palatal cusps.When the overcorrection amount for expansion reached 150%,the crown-root displacement in the upper first permanent molar,second primary molar,first primary molar,and primary cuspid were-0.109,-0.134,-0.132,and-0.298 mm,respectively.Applying specific torque compensation for different tooth positions can combat the buccal inclination of posterior teeth.At an overcorrection length of 150%(0.300 mm)with an added 1.3° root buccal torque,expansion efficiency was 56.15%,73.88%,79.49%,and 87.80%,respectively.While the crown-root displacement differences reduced to-0.081,-0.097,-0.095,and-0.208 mm.Conclusion·When using clear aligners for expansion treatment during a transitional dentition period,side effects such as buccal inclination of posterior teeth exist.Furthermore,various teeth realize differing levels of expansion efficiency,necessitating the design of unique adjustment strategies according to different tooth positions.Overcorrection can improve expansion efficiency but needs to be coordinated with root buccal torque for the whole tooth to move buccally.

To investigate the effect of the interval between neoadjuvant chemoradiotherapy (nCRT) and surgery on the clinical outcome of esophageal cancer. Methods    PubMed and EMbase databases from inception to March 2018 were retrieved by computer. A random-effect model was used for all meta-analyses irrespective of heterogeneity. The meta-analysis was performed by RevMan5.3 software. The primary outcomes were operative mortality, incidence of anastomotic leakage, and overall survival; secondary outcomes were pathologic complete remission rate, R0 resection rate, and positive resection margin rate. Results    A total of 17 studies with 18 173 patients were included. Among them, 13 were original studies with 2 950 patients, and 4 were database-based studies with a total of 15 223 patients. The results showed a significant positive correlation between the interval and operative mortality (Spearman coefficient=0.360, P=0.027). Dose-response meta-analysis revealed that there was a relatively better time window for  surgery after nCRT. Further analysis for primary outcomes at different time cut-offs found the following results: (1) when the time cut-off point within 30-70 days, the shorter interval was associated with a reduced operative mortality (7-8 weeks: RR=0.67, 95% CI 0.55-0.81, P<0.05; 30-46 days: RR=0.63, 95%CI 0.47-0.85, P<0.05; 60-70 days: RR=0.64, 95%CI 0.48-0.85, P<0.05); (2) when the time cut-off point within 30-46 days, the shorter interval correlated with a reduced incidence of anastomotic leakage (RR=0.39, 95%CI 0.21-0.72, P<0.05); when the time cut-off point within 7-8 weeks, the shorter interval could achieve a critical-level effect of reducing the incidence of anastomotic leakage (RR=0.73, 95%CI 0.52-1.03, P>0.05); (3) when the time cut-off point within 7-8 weeks, increased interval significantly was associated with the poor overall survival (HR=1.17, 95% CI 1.00-1.36, P<0.05). Secondary outcomes found that the shorter interval could significantly reduce the positive resection margin rate (RR=0.53, 95% CI 0.38-0.75, P<0.05) when time cut-off point within 56-60 days. Conclusion    Shortening the interval between nCRT and surgery can reduce the operative mortality, the incidence of anastomotic leakage, long-term mortality risk, and positive resection margin rate. It is recommended that surgery should be performed as soon as possible after the patient's physical recovery, preferably no more than 7-8 weeks, which supports the current study recommendation (within 3-8 weeks after nCRT).