OBJECTIVE:To confirm the effectiveness and safety of Shi's manipulation in treating acute and subacute neck pain patients.METHODS:This multicenter,positive controlled,randomized clinical trial has trial and contro...OBJECTIVE:To confirm the effectiveness and safety of Shi's manipulation in treating acute and subacute neck pain patients.METHODS:This multicenter,positive controlled,randomized clinical trial has trial and control groups.There were 240 patients randomly assigned to the trial group and the control group,and both groups received their respective intervention treatment methods for a period of 12 weeks.The time windows for clinical data collection were before treatment,immediately after treatment,3-d 1,2,4,8,and 12-week after treatment,and follow-up was conducted at 26 and 52-week after treatment.The observed indicators used include primary outcome index and secondary outcome index,with the primary outcome index being the assessment of neck pain severity,which is evaluated by patients using Numerical Rating Scale(NRS).Secondary secondary outcome index include,(a)cervical dysfunction index,measured by patients using the Neck Disability Index(NDI)for self-assessment;(b)Cervical activity measurement,measured through the cervical range of motion measurement program on Android mobile system;(c)Satisfaction treatment assessment,determined by the patient's self-evaluation;(d)Safety index,recorded the incidence of adverse reactions and adverse event.Results:The results showed that these efficacy indices were improved in different degrees in both groups.At immediate after intervention,there was significant difference in NRS,NDI,Cervical Range of Motion(ROM)between the two groups(P<0.01),the trial group was superior to the control group.At 3-d after intervention,there was significant difference in NRS,NDI,ROM between the two groups(P<0.01).At 1-week and 2-week after intervention,there was significant difference in NDI and ROM between the two groups(P<0.01).At 4-week and 6-week after intervention,there was significant difference in NDI,ROM between the two groups(P<0.05).At 8-week after intervention,there was significant difference in NDI,lateral-bending and axial-rotation ROM between the two groups(P<0.05).At 12-week after intervention,there was significant difference in NDI between the two groups(P<0.01).At 26-week and 52-week after intervention,there was significant difference in NDI,NRS between the two groups(P<0.01).In addition,the adverse reaction of trial group is significantly lower than that of control group(P<0.05).The satisfaction of patients in the trial group was better than that in the control group(P<0.01).CONCLUSION:Our findings suggest that Shi's manipulation can be a good complementary treatment option in patients with acute and subacute neck pain.展开更多
Serial-parallel manipulators are of great interest to academic community in recent years,especially those composed of classical parallel mechanisms.There have been many studies around 2(3RPS)and 2(3SPR)S-PMs,but unfor...Serial-parallel manipulators are of great interest to academic community in recent years,especially those composed of classical parallel mechanisms.There have been many studies around 2(3RPS)and 2(3SPR)S-PMs,but unfortunately their inverse kinematics have not yet been resolved.This paper discovers that the unknown kinematic parameters of middle platform are responsible for the unresolvable of inverse kinematics,meanwhile the unknown kinematic parameters of middle platform also have huge coupling relationships.Therefore,to break through this challenges,the huge coupling relationships are decoupled layer by layer,the kinematic parameters of middle platform are solved by combining Sylvester's elimination method,and the inverse displacements of 2(3RPS)and 2(3SPR)S-PMs are obtained subsequently.This paper not only solves the inverse kinematics of classical 2(3RPS)and 2(3SPR)S-PMs,but also reveals the essence of the inverse kinematics of general(3-DOF)+(3-DOF)6-DOF S-PMs and proposes a corresponding solution.展开更多
Hans Zempel1,2 TAU,a microtubule-associated protein,encoded by the microtubule-associated protein tau(MAPT)gene,is a central regulator of microtubule stability and axonal function in the human brain,with its pathologi...Hans Zempel1,2 TAU,a microtubule-associated protein,encoded by the microtubule-associated protein tau(MAPT)gene,is a central regulator of microtubule stability and axonal function in the human brain,with its pathological aggregation representing a hallmark of Alzheimer’s disease and related tauopathies.Despite extensive research into the role of TAU in neurodegeneration,its essentiality for human brain development has remained unclear.This perspective synthesizes recent genetic,molecular,and cellular evidence to demonstrate that the human brain-specific TAU isoform 0N3R is indispensable for proper neurodevelopment,pointing to loss-of-function of this isoform as a novel paradigm for TAU-associated disease.Alternative splicing of MAPT generates six brain-specific TAU isoforms,with 0N3R being exclusively expressed during fetal brain development.Analysis of large-scale human genetic datasets(gnomAD v4.0.0)reveals a high probability of loss-of-function intolerance(pLI=0.96)for the 0N3R isoform.This is in stark contrast to the canonical Matched Annotation from the NCBI and EMBL-EBI(MANE)transcript and peripheral“Big TAU,”both of which are tolerant to loss-of-function mutations.This intolerance is further supported by the scarcity of loss-of-function mutations in 0N3R-encoding exons and high missense constraint scores,suggesting strong evolutionary selection against disruption of this isoform.Functional studies using human induced pluripotent stem cell-derived cortical neurons with CRISPR-Cas9-mediated MAPT knockout reveal that,unlike in murine models where compensation by other microtubule-associated proteins occurs,loss of TAU in human neurons leads to deficits in neurite outgrowth,axon initial segment shortening,and a trend toward hyperexcitability,accompanied by broad transcriptomic changes affecting genes involved in microtubule organization and synaptic structure.Remarkably,re-expression of any of the six human brain-specific TAU isoforms rescues these phenotypes,underscoring their functional redundancy during development.These findings position the 0N3R isoform as essential for human brain development and suggest that loss-of-function mutations affecting this isoform likely result in neurodevelopmental impairment,potentially manifesting as intellectual disability without overt dysmorphic features.This contrasts with the apparent tolerance to MAPT loss-of-function in mice and peripheral tissues,highlighting a critical species-and isoform-specific requirement for TAU in human neurodevelopment.The hypothesis of 0N3R-TAU loss-of-function intolerance opens new avenues for understanding neurodevelopmental disorders and refines the conceptual framework of TAU-associated disease mechanisms beyond toxic gain-of-function.展开更多
基金the National Natural Science Foundation of China:Biomechanical Mechanism of Tendon Off-position and Joint Subluxation and Manual Treatment for Adolescent Neck Pain(No.82374467)the Research on the Mechanism of Manipulation to Regulate Internalizing Integrin and its Downstream Focal Adhesion Kinase/Ras Homolog Gene Family Member A/Rho-associated Coiled-coil Containing Protein Kinase 1 Signaling Pathway to Repair Chronic Skeletal Muscle Injury(No.82374481)the Mechanism of Huaizhen Nourishing the Liver Capsule to Maintain the Balance of Knee Joint from the Coupling and Interaction of Skeletal Muscle-subchondral Bone Dynamics Rresponse(No.81704103)。
文摘OBJECTIVE:To confirm the effectiveness and safety of Shi's manipulation in treating acute and subacute neck pain patients.METHODS:This multicenter,positive controlled,randomized clinical trial has trial and control groups.There were 240 patients randomly assigned to the trial group and the control group,and both groups received their respective intervention treatment methods for a period of 12 weeks.The time windows for clinical data collection were before treatment,immediately after treatment,3-d 1,2,4,8,and 12-week after treatment,and follow-up was conducted at 26 and 52-week after treatment.The observed indicators used include primary outcome index and secondary outcome index,with the primary outcome index being the assessment of neck pain severity,which is evaluated by patients using Numerical Rating Scale(NRS).Secondary secondary outcome index include,(a)cervical dysfunction index,measured by patients using the Neck Disability Index(NDI)for self-assessment;(b)Cervical activity measurement,measured through the cervical range of motion measurement program on Android mobile system;(c)Satisfaction treatment assessment,determined by the patient's self-evaluation;(d)Safety index,recorded the incidence of adverse reactions and adverse event.Results:The results showed that these efficacy indices were improved in different degrees in both groups.At immediate after intervention,there was significant difference in NRS,NDI,Cervical Range of Motion(ROM)between the two groups(P<0.01),the trial group was superior to the control group.At 3-d after intervention,there was significant difference in NRS,NDI,ROM between the two groups(P<0.01).At 1-week and 2-week after intervention,there was significant difference in NDI and ROM between the two groups(P<0.01).At 4-week and 6-week after intervention,there was significant difference in NDI,ROM between the two groups(P<0.05).At 8-week after intervention,there was significant difference in NDI,lateral-bending and axial-rotation ROM between the two groups(P<0.05).At 12-week after intervention,there was significant difference in NDI between the two groups(P<0.01).At 26-week and 52-week after intervention,there was significant difference in NDI,NRS between the two groups(P<0.01).In addition,the adverse reaction of trial group is significantly lower than that of control group(P<0.05).The satisfaction of patients in the trial group was better than that in the control group(P<0.01).CONCLUSION:Our findings suggest that Shi's manipulation can be a good complementary treatment option in patients with acute and subacute neck pain.
基金Supported by National Natural Science Foundation of China(Grant No.52275033)National Natural Science Youth Foundation of China(Grant No.52205033)Hebei Provincial Natural Science Foundation of China(Grant No.E2021203019)。
文摘Serial-parallel manipulators are of great interest to academic community in recent years,especially those composed of classical parallel mechanisms.There have been many studies around 2(3RPS)and 2(3SPR)S-PMs,but unfortunately their inverse kinematics have not yet been resolved.This paper discovers that the unknown kinematic parameters of middle platform are responsible for the unresolvable of inverse kinematics,meanwhile the unknown kinematic parameters of middle platform also have huge coupling relationships.Therefore,to break through this challenges,the huge coupling relationships are decoupled layer by layer,the kinematic parameters of middle platform are solved by combining Sylvester's elimination method,and the inverse displacements of 2(3RPS)and 2(3SPR)S-PMs are obtained subsequently.This paper not only solves the inverse kinematics of classical 2(3RPS)and 2(3SPR)S-PMs,but also reveals the essence of the inverse kinematics of general(3-DOF)+(3-DOF)6-DOF S-PMs and proposes a corresponding solution.
文摘Hans Zempel1,2 TAU,a microtubule-associated protein,encoded by the microtubule-associated protein tau(MAPT)gene,is a central regulator of microtubule stability and axonal function in the human brain,with its pathological aggregation representing a hallmark of Alzheimer’s disease and related tauopathies.Despite extensive research into the role of TAU in neurodegeneration,its essentiality for human brain development has remained unclear.This perspective synthesizes recent genetic,molecular,and cellular evidence to demonstrate that the human brain-specific TAU isoform 0N3R is indispensable for proper neurodevelopment,pointing to loss-of-function of this isoform as a novel paradigm for TAU-associated disease.Alternative splicing of MAPT generates six brain-specific TAU isoforms,with 0N3R being exclusively expressed during fetal brain development.Analysis of large-scale human genetic datasets(gnomAD v4.0.0)reveals a high probability of loss-of-function intolerance(pLI=0.96)for the 0N3R isoform.This is in stark contrast to the canonical Matched Annotation from the NCBI and EMBL-EBI(MANE)transcript and peripheral“Big TAU,”both of which are tolerant to loss-of-function mutations.This intolerance is further supported by the scarcity of loss-of-function mutations in 0N3R-encoding exons and high missense constraint scores,suggesting strong evolutionary selection against disruption of this isoform.Functional studies using human induced pluripotent stem cell-derived cortical neurons with CRISPR-Cas9-mediated MAPT knockout reveal that,unlike in murine models where compensation by other microtubule-associated proteins occurs,loss of TAU in human neurons leads to deficits in neurite outgrowth,axon initial segment shortening,and a trend toward hyperexcitability,accompanied by broad transcriptomic changes affecting genes involved in microtubule organization and synaptic structure.Remarkably,re-expression of any of the six human brain-specific TAU isoforms rescues these phenotypes,underscoring their functional redundancy during development.These findings position the 0N3R isoform as essential for human brain development and suggest that loss-of-function mutations affecting this isoform likely result in neurodevelopmental impairment,potentially manifesting as intellectual disability without overt dysmorphic features.This contrasts with the apparent tolerance to MAPT loss-of-function in mice and peripheral tissues,highlighting a critical species-and isoform-specific requirement for TAU in human neurodevelopment.The hypothesis of 0N3R-TAU loss-of-function intolerance opens new avenues for understanding neurodevelopmental disorders and refines the conceptual framework of TAU-associated disease mechanisms beyond toxic gain-of-function.
