Osteopetrosis is an inherited metabolic disease,characterized by increased bone density and narrow marrow cavity.Patients with severe osteopetrosis exhibit abnormal bone brittleness,anemia,and infection complications,...Osteopetrosis is an inherited metabolic disease,characterized by increased bone density and narrow marrow cavity.Patients with severe osteopetrosis exhibit abnormal bone brittleness,anemia,and infection complications,which commonly cause death within the first decade of life.Pathologically,osteopetrosis impairs not only the skeletal system,but also the hemopoietic and immune systems during development,while the underlying osteoimmunological mechanisms remain unclear.Osteoclastic mutations are regarded as the major causes of osteopetrosis,while osteoclast non-autonomous theories have been proposed in recent years with unclear underlying mechanisms.Retinoic acid(RA),the metabolite of Vitamin A,is an essential requirement for skeletal and hematopoietic development,through the activation of retinoic acid signaling.RA can relieve osteopetrosis symptoms in some animal models,while its effect on bone health is still controversial and the underlying mechanisms remain unclear.In this study,we constructed an osteoblast-specific inhibitory retinoic acid signaling mouse model and surprisingly found it mimicked the symptoms of osteopetrosis found in clinical cases:dwarfism,increased imperfectly-formed trabecular bone deposition with a reduced marrow cavity,thin cortical bone with a brittle skeleton,and hematopoietic and immune dysfunction.Micro-CT,the three-point bending test,and histological analysis drew a landscape of poor bone quality.Single-cell RNA sequencing(scRNA-seq)of the femur and RNA-seq of osteoblasts uncovered an atlas of pathological skeletal metabolism dysfunction in the mutant mice showing that osteogenesis was impaired in a cell-autonomous manner and osteoclastogenesis was impaired via osteoblast-osteoclast crosstalk.Moreover,scRNA-seq of bone marrow and flow cytometry of peripheral blood,spleen,and bone marrow uncovered pathology in the hematopoietic and immune systems in the mutant mice,mimicking human osteopetrosis.Results showed that hematopoietic progenitors and B lymphocyte differentiation were affected and the osteoblast-dominated cell crosstalk was impaired,which may result from transcriptional impairment of the ligands Pdgfd and Sema4d.In summary,we uncovered previously unreported pathogenesis of osteopetrosis-like disorder in mice with skeletal,hematopoietic,and immune system dysfunction,which was induced by the inhibition of retinoic acid signaling in osteoblasts,and sheds new insights into a potential treatment for osteopetrosis.展开更多
Subjects with Bell＇s palsy and healthy individuals were treated with moxibustion thermal stimulation on the Hegu （LI4） acupoint; an infrared thermal imaging system was used to observe facial-temperature changes. B...Subjects with Bell＇s palsy and healthy individuals were treated with moxibustion thermal stimulation on the Hegu （LI4） acupoint; an infrared thermal imaging system was used to observe facial-temperature changes. Bell＇s palsy patients developed low or high temperatures at the affected side, with poor symmetry. Healthy people showed high temperatures on the forehead, medial angle of the eye, nasal ala and around the lips, but low temperatures on bilateral cheeks, thus forming a ＂T-type hot area＂ in the face, with good temperature symmetry. Moxibustion treatment for 11 minutes significantly improved high asymmetry in temperature in the faces of Bell＇s palsy patients. This evidence indicates that moxibustion treatment on Hegu enables increases in facial temperatures in healthy people and Bell＇s palsy patients, especially around the lips. Moxibustion stimulation at the Hegu not only improves the global circulation but also has specific effects on the lips in Bell＇s palsy patients, but the underlying mechanism needs further investigation.展开更多
OBJECTIVE:To study the effects of temperature on different facial areas by suspended moxibustion at two points,Zusanli(ST 36) and Hegu(LI 4),and probe the phenomena underlying self-regulation in the human body after t...OBJECTIVE:To study the effects of temperature on different facial areas by suspended moxibustion at two points,Zusanli(ST 36) and Hegu(LI 4),and probe the phenomena underlying self-regulation in the human body after thermal stimulation.METHODS:Thirty healthy volunteers accepted moxibustion over Zusanli(ST 36) and Hegu(LI 4),and the order of moxibustion points was randomly determined.Moxibustion method:suspension of moxibustion over Zusanli(ST 36) and Hegu(LI 4) on both sides was performed using an ignited moxa stick stuck in a support for 20 min.Observation method:An infrared thermal image of the face was taken before and after suspended moxibustion using a CK350 medical infrared thermal imaging instrument.Data analysis:A thermal microscopic section view system(TMTSys) was used to analyze the change in temperature in special facial areas.Statistical analysis was carried out using SPSS 14.0 software.RESULTS:Before moxibustion was suspended,the facial thermal image showed a T-shaped thermal area related to the vascular distribution with even temperature and good symmetry on both sides.Suspended moxibustion over Zusanli(ST 36) have a very significant increase in temperature at the forehead,around the nose,at the corners of the mouth,and at the cheeks and lips(P<0.01).Suspended moxibustion over Hegu(LI 4) also have a significant(P<0.05) increase in temperature around the nose,the corners of the mouth,the cheeks,and lips,where has a new high temperature area was formed(P<0.01).Suspended moxibustion over Hegu(LI 4) raised the temperature at the middle point of the lips more obviously than did Zusanli(ST 36) in the same person,(P<0.05).After 10 min of moxibustion over Zusanli(ST 36) and Hegu(LI 4),the change in temperature in the facial area reached its peak value.CONCLUSIONS:Facial infrared thermography of healthy people revealed a T-shaped thermal area reflecting a physiological thermal area.Moxibustion over Zusanli(ST 36) or Hegu(LI 4) raised the temperature in this facial T-shaped thermal area.Hegu(LI 4) led to the formation of a new thermal area in the lips.The time required for moxibustion to regulate human body temperature was 10 min.展开更多
Chromosome aberrations are distinctive features of human malignant tumors. Analysis of chromosomal changes can illuminate the molecular mechanisms underlying the development and progression of cancer. To establish the...Chromosome aberrations are distinctive features of human malignant tumors. Analysis of chromosomal changes can illuminate the molecular mechanisms underlying the development and progression of cancer. To establish the technique of multicolor fluorescence in situ hybridization （M-FISH） for identifying chromosome aberrations in esophageal carcinoma cell line KYSE 410-4, four pools of 6-color whole-chromosome painting probes have been designed and hybridized on the same metaphase spread by four rounds of repetitive FISH. Repetitive 6-color M-FISH was successfully established and the cytogenetic abnormalities in KYSE 410-4 cells were characterized. Chromosome gains occurred at 2q, 3, 8, 17p, and X. An isochromosome 3q was visualized in the cell line, which might be one intermediate mechanism leading to 3p losses and/or 3q gains. Furthermore, 16 structural arrangements were detected, including four derivative chromosomes. The rearrangement of the centromeric regions accounted for approximately 44% of all rearrangements. The results added a more complete and accurate information of the genetic alterations to the classical cytogenetic description of KYSE 410-4 and provided a detailed cytogenetic background data for appropriate use of the cell line. The established 6-color M-FISH was useful for analyzing chromosomes in the whole genome of human tumors.展开更多
OBJECTIVE: To investigate the effect of moxibustion on Zusanli(ST 36) on visceral-mesenteric vesselsbyobservingcirculation.METHODS: Forty-five SD rats were randomly assigned to a moxibustion, electroacupuncture(EA),an...OBJECTIVE: To investigate the effect of moxibustion on Zusanli(ST 36) on visceral-mesenteric vesselsbyobservingcirculation.METHODS: Forty-five SD rats were randomly assigned to a moxibustion, electroacupuncture(EA),and blank group. In the moxibustion group, heat stimulation of moxibustion to the Zusanli(ST36)area of normal rats was performed for 15 min. In the EA group, needles were inserted into the Zusanli(ST36)and later alpoint[0.5 cm lateral from Zusanli(ST 36)] for 15 min. The blank group was not given any treatment. We continuously monitored mesenteric microvascular changes with invivo microscopicvideo.RESULTS:Moxibustion and EA to Zusanli(ST 36) increase the diameter of mesenteric arterioles and venules(P<0.05). There were no obvious changes in the blank group. Fine arterial diameter peaked at12 min in the moxibustion group, while it peaked at15 min in the EA group.CONCLUSION:The stimulation of moxibustion and acupuncture to Zusanli(ST 36) has immediate effects on expanding the microvasculature. This dilation may be the mechanism of the gastrointestinal effect of Zusanli(ST36).展开更多
In this paper,we extend the δ^(-)-steepest descent method to study the Cauchy problem for the nonlocal nonlinear Schrödinger(NNLS)equation with weighted Sobolev initial data iqt+qxx+2σq^(2)(x,t)q(−x,t)=0,q(x,0)...In this paper,we extend the δ^(-)-steepest descent method to study the Cauchy problem for the nonlocal nonlinear Schrödinger(NNLS)equation with weighted Sobolev initial data iqt+qxx+2σq^(2)(x,t)q(−x,t)=0,q(x,0)=q0(x),where q0∈H^(1,1)(R).Based on the spectral analysis of the Lax pair,the solution of the Cauchy problem is expressed in terms of the solution of a Riemann-Hilbert problem,which is transformed into a solvable model after a series of deformations.We further obtain the asymptotic expansion of the solution to the Cauchy problem for the NNLS equation in the solitonic region.The leading term is soliton solutions,the second term is the interaction between solitons and dispersion,and the error term comes from a corresponding δ^(-)-problem.Compared with the asymptotic results on the classical NLS equation,the major difference is the second and third terms of the asymptotic expansion for the NNLS equation,which were affected by a function depending on the scattering data and the stationary phase point.展开更多
In this paper,the authors apply■steepest descent method to study the Cauchy problem for the derivative nonlinear Schrödinger equation with finite density type initial data iqt+qxx+1(lq|^(2)q)_(x)=0,q(x,0)=q0(x),...In this paper,the authors apply■steepest descent method to study the Cauchy problem for the derivative nonlinear Schrödinger equation with finite density type initial data iqt+qxx+1(lq|^(2)q)_(x)=0,q(x,0)=q0(x),where lim x→±∞ qo(x)=g0(x)=q±and|q±|=1.Based on the spectral analysis of the Lax pair,they express the solution of the derivative Schrödinger equation in terms of solutions of a Riemann-Hilbert problem.They compute the long time asymptotic expansion of the solution in differeit space-time regions.For the regionζ=x/t with|ζ+2|<1,the long time asymptotic is given by q(x,t)=T(∞)^(-2)q^(r)Λ(x,t)+O(t^(-3/4)),in which the leading term is N(I)solitons,the second term is a residual error from a■equation.For the regionζ+2|>1,the long time asymptotic is given by q(x,t)=t(∞)^(-2)q^(r)Λ(x,t)-t^(-1/2)if11+O(t^(-3/4)) in which the leading term is N(I)solitons,the second t^(-1/2)order term is soliton-radiation interactions and the third term is a residual error from a■equation.These results are verification of the soliton resolution conjectuore for the derivative Schrödinger equation.In their case of finite density type initial data,the phase functionθ(z)is more complicated that in finite mass initial data.Moreover,two triangular decompositions of the jump matrix are used to open jump lines on the whole real axis and imaginary axis,respectively.展开更多
基金supported in part by grants from the Hainan Provincial Natural Science Foundation of China (824MS152)the National Natural Science Foundation of China (81870740,82071083,82271006,82101048)+9 种基金the National Science Foundation of Shanghai (21ZR1436900,22ZR1436700)the Program of Shanghai Academic/Technology Research Leader (20XD1422300)the Cross-Disciplinary Research Fund of Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine (JYJC202116,JYJC201902)the Project of Biobank of Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine (YBKB201909,YBKB202216)the Original Exploration Project of Shanghai Ninth People’s Hospital,Shanghai Jiao Tong University School of Medicine (JYYC003)the Clinical Research Plan of SHDC (SHDC2020CR4084)the Biomaterials and Regenerative Medicine Institute Cooperative Research Project Shanghai Jiao Tong University School of Medicine (2022LHB02)Two-Hundred Talent Project of Shanghai Jiao Tong University School of Medicine (20221809)Shanghai Jiao Tong University’s“Jiaotong University Star”Program Medical and Industrial Cross Research Fund (YG2023ZD14)Shanghai Science and Technology Innovation Action Plan-International Science and Technology Cooperation Program (23410713600)。
文摘Osteopetrosis is an inherited metabolic disease,characterized by increased bone density and narrow marrow cavity.Patients with severe osteopetrosis exhibit abnormal bone brittleness,anemia,and infection complications,which commonly cause death within the first decade of life.Pathologically,osteopetrosis impairs not only the skeletal system,but also the hemopoietic and immune systems during development,while the underlying osteoimmunological mechanisms remain unclear.Osteoclastic mutations are regarded as the major causes of osteopetrosis,while osteoclast non-autonomous theories have been proposed in recent years with unclear underlying mechanisms.Retinoic acid(RA),the metabolite of Vitamin A,is an essential requirement for skeletal and hematopoietic development,through the activation of retinoic acid signaling.RA can relieve osteopetrosis symptoms in some animal models,while its effect on bone health is still controversial and the underlying mechanisms remain unclear.In this study,we constructed an osteoblast-specific inhibitory retinoic acid signaling mouse model and surprisingly found it mimicked the symptoms of osteopetrosis found in clinical cases:dwarfism,increased imperfectly-formed trabecular bone deposition with a reduced marrow cavity,thin cortical bone with a brittle skeleton,and hematopoietic and immune dysfunction.Micro-CT,the three-point bending test,and histological analysis drew a landscape of poor bone quality.Single-cell RNA sequencing(scRNA-seq)of the femur and RNA-seq of osteoblasts uncovered an atlas of pathological skeletal metabolism dysfunction in the mutant mice showing that osteogenesis was impaired in a cell-autonomous manner and osteoclastogenesis was impaired via osteoblast-osteoclast crosstalk.Moreover,scRNA-seq of bone marrow and flow cytometry of peripheral blood,spleen,and bone marrow uncovered pathology in the hematopoietic and immune systems in the mutant mice,mimicking human osteopetrosis.Results showed that hematopoietic progenitors and B lymphocyte differentiation were affected and the osteoblast-dominated cell crosstalk was impaired,which may result from transcriptional impairment of the ligands Pdgfd and Sema4d.In summary,we uncovered previously unreported pathogenesis of osteopetrosis-like disorder in mice with skeletal,hematopoietic,and immune system dysfunction,which was induced by the inhibition of retinoic acid signaling in osteoblasts,and sheds new insights into a potential treatment for osteopetrosis.
基金supported by the National Natural Science Foundation of China,No.30973795
文摘Subjects with Bell＇s palsy and healthy individuals were treated with moxibustion thermal stimulation on the Hegu （LI4） acupoint; an infrared thermal imaging system was used to observe facial-temperature changes. Bell＇s palsy patients developed low or high temperatures at the affected side, with poor symmetry. Healthy people showed high temperatures on the forehead, medial angle of the eye, nasal ala and around the lips, but low temperatures on bilateral cheeks, thus forming a ＂T-type hot area＂ in the face, with good temperature symmetry. Moxibustion treatment for 11 minutes significantly improved high asymmetry in temperature in the faces of Bell＇s palsy patients. This evidence indicates that moxibustion treatment on Hegu enables increases in facial temperatures in healthy people and Bell＇s palsy patients, especially around the lips. Moxibustion stimulation at the Hegu not only improves the global circulation but also has specific effects on the lips in Bell＇s palsy patients, but the underlying mechanism needs further investigation.
基金Supported by the National Natural Science Foundation (No.30973795)
文摘OBJECTIVE:To study the effects of temperature on different facial areas by suspended moxibustion at two points,Zusanli(ST 36) and Hegu(LI 4),and probe the phenomena underlying self-regulation in the human body after thermal stimulation.METHODS:Thirty healthy volunteers accepted moxibustion over Zusanli(ST 36) and Hegu(LI 4),and the order of moxibustion points was randomly determined.Moxibustion method:suspension of moxibustion over Zusanli(ST 36) and Hegu(LI 4) on both sides was performed using an ignited moxa stick stuck in a support for 20 min.Observation method:An infrared thermal image of the face was taken before and after suspended moxibustion using a CK350 medical infrared thermal imaging instrument.Data analysis:A thermal microscopic section view system(TMTSys) was used to analyze the change in temperature in special facial areas.Statistical analysis was carried out using SPSS 14.0 software.RESULTS:Before moxibustion was suspended,the facial thermal image showed a T-shaped thermal area related to the vascular distribution with even temperature and good symmetry on both sides.Suspended moxibustion over Zusanli(ST 36) have a very significant increase in temperature at the forehead,around the nose,at the corners of the mouth,and at the cheeks and lips(P<0.01).Suspended moxibustion over Hegu(LI 4) also have a significant(P<0.05) increase in temperature around the nose,the corners of the mouth,the cheeks,and lips,where has a new high temperature area was formed(P<0.01).Suspended moxibustion over Hegu(LI 4) raised the temperature at the middle point of the lips more obviously than did Zusanli(ST 36) in the same person,(P<0.05).After 10 min of moxibustion over Zusanli(ST 36) and Hegu(LI 4),the change in temperature in the facial area reached its peak value.CONCLUSIONS:Facial infrared thermography of healthy people revealed a T-shaped thermal area reflecting a physiological thermal area.Moxibustion over Zusanli(ST 36) or Hegu(LI 4) raised the temperature in this facial T-shaped thermal area.Hegu(LI 4) led to the formation of a new thermal area in the lips.The time required for moxibustion to regulate human body temperature was 10 min.
基金Acknowledgements This study was supported by the National Science Foundation （No. 30630067）；the State Key Basic Research Grant of China （No. 2004CB518705）； the Program for Changjiang Scholars and Innovative Research Team in University （No. IRT0416）.
文摘Chromosome aberrations are distinctive features of human malignant tumors. Analysis of chromosomal changes can illuminate the molecular mechanisms underlying the development and progression of cancer. To establish the technique of multicolor fluorescence in situ hybridization （M-FISH） for identifying chromosome aberrations in esophageal carcinoma cell line KYSE 410-4, four pools of 6-color whole-chromosome painting probes have been designed and hybridized on the same metaphase spread by four rounds of repetitive FISH. Repetitive 6-color M-FISH was successfully established and the cytogenetic abnormalities in KYSE 410-4 cells were characterized. Chromosome gains occurred at 2q, 3, 8, 17p, and X. An isochromosome 3q was visualized in the cell line, which might be one intermediate mechanism leading to 3p losses and/or 3q gains. Furthermore, 16 structural arrangements were detected, including four derivative chromosomes. The rearrangement of the centromeric regions accounted for approximately 44% of all rearrangements. The results added a more complete and accurate information of the genetic alterations to the classical cytogenetic description of KYSE 410-4 and provided a detailed cytogenetic background data for appropriate use of the cell line. The established 6-color M-FISH was useful for analyzing chromosomes in the whole genome of human tumors.
基金Supported by Natural Science Foundation-funded Project:the Discussion of Laws And Mechanisms of Moxibustion Zusanli(ST 36)To Stimulate Research Targeted Surface Thermal Effects(No.30973795)
文摘OBJECTIVE: To investigate the effect of moxibustion on Zusanli(ST 36) on visceral-mesenteric vesselsbyobservingcirculation.METHODS: Forty-five SD rats were randomly assigned to a moxibustion, electroacupuncture(EA),and blank group. In the moxibustion group, heat stimulation of moxibustion to the Zusanli(ST36)area of normal rats was performed for 15 min. In the EA group, needles were inserted into the Zusanli(ST36)and later alpoint[0.5 cm lateral from Zusanli(ST 36)] for 15 min. The blank group was not given any treatment. We continuously monitored mesenteric microvascular changes with invivo microscopicvideo.RESULTS:Moxibustion and EA to Zusanli(ST 36) increase the diameter of mesenteric arterioles and venules(P<0.05). There were no obvious changes in the blank group. Fine arterial diameter peaked at12 min in the moxibustion group, while it peaked at15 min in the EA group.CONCLUSION:The stimulation of moxibustion and acupuncture to Zusanli(ST 36) has immediate effects on expanding the microvasculature. This dilation may be the mechanism of the gastrointestinal effect of Zusanli(ST36).
基金supported by National Natural Science Foundation of China(Grant Nos.12271104,51879045,12247182).
文摘In this paper,we extend the δ^(-)-steepest descent method to study the Cauchy problem for the nonlocal nonlinear Schrödinger(NNLS)equation with weighted Sobolev initial data iqt+qxx+2σq^(2)(x,t)q(−x,t)=0,q(x,0)=q0(x),where q0∈H^(1,1)(R).Based on the spectral analysis of the Lax pair,the solution of the Cauchy problem is expressed in terms of the solution of a Riemann-Hilbert problem,which is transformed into a solvable model after a series of deformations.We further obtain the asymptotic expansion of the solution to the Cauchy problem for the NNLS equation in the solitonic region.The leading term is soliton solutions,the second term is the interaction between solitons and dispersion,and the error term comes from a corresponding δ^(-)-problem.Compared with the asymptotic results on the classical NLS equation,the major difference is the second and third terms of the asymptotic expansion for the NNLS equation,which were affected by a function depending on the scattering data and the stationary phase point.
基金supported by the National Natural Science Foundation of China(Nos.51879045,1202624,118013233,11671095)。
文摘In this paper,the authors apply■steepest descent method to study the Cauchy problem for the derivative nonlinear Schrödinger equation with finite density type initial data iqt+qxx+1(lq|^(2)q)_(x)=0,q(x,0)=q0(x),where lim x→±∞ qo(x)=g0(x)=q±and|q±|=1.Based on the spectral analysis of the Lax pair,they express the solution of the derivative Schrödinger equation in terms of solutions of a Riemann-Hilbert problem.They compute the long time asymptotic expansion of the solution in differeit space-time regions.For the regionζ=x/t with|ζ+2|<1,the long time asymptotic is given by q(x,t)=T(∞)^(-2)q^(r)Λ(x,t)+O(t^(-3/4)),in which the leading term is N(I)solitons,the second term is a residual error from a■equation.For the regionζ+2|>1,the long time asymptotic is given by q(x,t)=t(∞)^(-2)q^(r)Λ(x,t)-t^(-1/2)if11+O(t^(-3/4)) in which the leading term is N(I)solitons,the second t^(-1/2)order term is soliton-radiation interactions and the third term is a residual error from a■equation.These results are verification of the soliton resolution conjectuore for the derivative Schrödinger equation.In their case of finite density type initial data,the phase functionθ(z)is more complicated that in finite mass initial data.Moreover,two triangular decompositions of the jump matrix are used to open jump lines on the whole real axis and imaginary axis,respectively.
