Objective:Comorbid pain and depression are common but remain difficult to treat.Electroacupuncture(EA)can effectively improve symptoms of depression and relieve pain,but its neural mechanism remains unclear.Therefore,...Objective:Comorbid pain and depression are common but remain difficult to treat.Electroacupuncture(EA)can effectively improve symptoms of depression and relieve pain,but its neural mechanism remains unclear.Therefore,we used resting-state functional magnetic resonance imaging(rs-fMRI)to detect cerebral changes after initiating a mouse pain model via constriction of the infraorbital nerve(CION)and then treating these animals with EA.Methods:Forty male C57BL/6J mice were divided into 4 groups:control,CION model,EA,and sham acupuncture(without needle insertion).EA was performed on the acupoints Baihui(GV20)and Zusanli(ST36)for 20 min,once a day for 10 consecutive days.The mechanical withdrawal threshold was tested3 days after the surgery and every 3 days after the intervention.The depressive behavior was evaluated with the tail suspension test,open-field test,elevated plus maze(EPM),sucrose preference test,and marble burying test.The rs-fMRI was used to detect the cerebral changes of the functional connectivity(FC)in the mice following EA treatment.Results:Compared with the CION group,the mechanical withdrawal threshold increased in the EA group at the end of the intervention(P<0.05);the immobility time in tail suspension test decreased(P<0.05);and the times of the open arm entry and the open arm time in the EPM increased(both P<0.001).There was no difference in the sucrose preference or marble burying tests(both P>0.05).The fMRI results showed that EA treatment downregulated the amplitude of low-frequency fluctuations and regional homogeneity values,while these indicators were elevated in brain regions including the amygdala,hippocampus and cerebral cortex in the CION model for comorbid pain and depression.Selecting the amygdala as the seed region,we found that the FC was higher in the CION group than in the control group.Meanwhile,EA treatment was able to decrease the FC between the amygdala and other brain regions including the caudate putamen,thalamus,and parts of the cerebral cortex.Conclusion:EA can downregulate the abnormal activation of neurons in the amygdala and improve its FC with other brain regions,thus exerting analgesic and antidepressant effects.Please cite this article as:Yin X,Zeng XL,Lin JJ,Xu WQ,Cui KY,Guo XT,Li W,Xu SF.Brain functional changes following electroacupuncture in a mouse model of comorbid pain and depression:A restingstate functional magnetic resonance imaging study.展开更多
Background Acupuncture and its related therapies,as an important part of traditional Chinese medicine,have been widely accepted by the public and healthcare professionals all over the world.According to previous revie...Background Acupuncture and its related therapies,as an important part of traditional Chinese medicine,have been widely accepted by the public and healthcare professionals all over the world.According to previous reviews,the department of acupuncture is a potential place where nosocomial infection might occur.Objectives To investigate the common pathogens and possible risk factors for nosocomial infection,figure out the measures and strategies for control and prevention,and provide general reporting guideline for future cases.Methods A systematic literature search of 6 libraries(EMBASE,CINAHL,PubMed,VIP,CNKI,SinoMed)was carried out on nosocomial infection(NIs)after acupuncture and its related therapies(e.g.,moxibustion,cupping,massage,dry needling)published from January 1,2012 to August 31,2023.Studies providing primary data were included;reviews,comments,and non-primary data studies were excluded to prevent duplicate case analysis.Data on bibliographic details,study characteristics,and clinical information were extracted.Results were synthesized through tabulation and categorized by therapy type,country income level,symptoms/diagnoses,pathogens,risk factors,treatments,and outcomes.Conclusion Nosocomial infections after acupuncture and its related therapies are possible but preventable.Prevention measures can be carried out in terms of the risk factors listed above.Future case reports are suggested to provide specific details of infection,including the setting,qualification,treatment,disinfection,and causal evidence.展开更多
Background:Hemorrhoids are one of the most common conditions that lead to surgery,and until now surgical hemorrhoidectomy has been the major effective treatment.Post-operative pain from hemorrhoidectomy has been exper...Background:Hemorrhoids are one of the most common conditions that lead to surgery,and until now surgical hemorrhoidectomy has been the major effective treatment.Post-operative pain from hemorrhoidectomy has been experienced by thousands of patients and remains a major inconvenience of the operation.Objective:This study evaluates the clinical efficacy of the pestle needle therapy,an acupoint stimulation method,for relief of post-hemorrhoidectomy pain.Design,setting,participants and interventions:This was a single-center,patient-assessor-blinded and randomized controlled trial with 154 patients receiving Milligan hemorrhoidectomy surgery.Eligible patients were randomly assigned to either a treatment group or a control group at a ratio of 1:1.The treatment group received the pestle needle therapy,with manual stimulation at Yaoshu(DU2),Mingmen(DU4),Changqiang(DU1),Chengshan(BL57),Erbai(EX-UE2)and the perianal points(1,3,5,7,9,and 11 o’clock around the lesion);while the control group received a sham treatment with very light pressure.Three sessions of treatment were performed at 30 min,4 h and 12 h after the surgery,and each lasted for 15 min.Main outcome measures:The primary outcome was post-operative pain measured with the visual analogue scale(VAS)at 12 h after surgery.The secondary outcomes included the VAS scores measured at0.5,2,4,6,8,24 and 48 h after surgery,the analgesic dose,the time and the VAS score of the patients’first defecation after surgery,as well as the Hamilton Rating Scale for Anxiety(HAMA)evaluated before discharge.Results:The mean pain score of the treatment group was significantly lower than that of the control group(3.10±1.27 vs 4.82±1.29;P<0.001)at 12 h after surgery.Compared with the control group,patients in the treatment group needed a smaller dose of analgesic within the first 24 hours after surgery(P=0.002);and their HAMA scores before discharge were lower(4.07±2.40 vs 5.10±2.45,P=0.009).Compared to the treatment group,patients in the control group had a greater time to the first defecation after surgery([52.34±15.72]h vs[27.08±13.68]h;P<0.001),but there was no difference in their VAS scores at the first defecation(P=0.092).Conclusion:The pestle needle therapy was effective for relieving pain,reducing anxiety and improving bowel function after hemorrhoidectomy,and it is worthy of clinical application.展开更多
Background:The outbreak of coronavirus disease 2019(COVID-19)infection posed a huge threat and burden to public healthcare in late 2022.Non-drug measures of traditional Chinese medicine(TCM),such as acupuncture,cuppin...Background:The outbreak of coronavirus disease 2019(COVID-19)infection posed a huge threat and burden to public healthcare in late 2022.Non-drug measures of traditional Chinese medicine(TCM),such as acupuncture,cupping and moxibustion,are commonly used as adjuncts in China to help in severe cases,but their effects remain unclear.Objectives:To observe the clinical effect of TCM non-drug measures in improving respiratory function and symptoms among patients with severe COVID-19.Design,setting,participants and interventions:This study was designed as a multicenter,assessor-blind,randomized controlled trial.Hospitalized patients with COVID-19 were randomly assigned to the treatment or control group.The treatment group received individualized TCM non-drug measures in combination with prone position ventilation,while the control group received prone position ventilation only for 5 consecutive days.Main outcome measures:The primary outcome measures were the percentage of patients with improved oxygen saturation(SpO_(2))at the end of the 5-day intervention,as well as changes of patients'respiratory rates.The secondary outcome measures included changes in SpO_(2)and total score on the self-made respiratory symptom scale.The improvement rate,defined as a 3-day consecutive increase in SpO_(2),the duration of prone positioning,and adverse events were recorded as well.Results:Among the 198 patients included in the intention-to-treat analysis,159(80.3%)completed all assessments on day 5,and 39(19.7%)patients withdrew from the study.At the end of the intervention,71(91%)patients in the treatment group had SpO_(2)above 93%,while 61(75.3%)in the control group reached this level.The proportion of participant with improved SpO_(2)was significantly greater in the intervention group(mean difference[MD]=15.7;95%confidence interval[CI]:4.4,27.1;P=0.008).Compared to the baseline,with daily treatment there were significant daily decreases in respiratory rates in both groups,but no statistical differences between groups were found(all P≥0.05).Compared to the control group,the respiratory-related symptoms score was lower among patients in the treatment group(MD=-1.7;95%CI:-2.8,-0.5;P=0.008)after day 3 of treatment.A gradual decrease in the total scores of both groups was also observed.Thirty-one adverse events occurred during the intervention,and 2patients were transferred to the intensive care unit due to deterioration of their illness.Conclusion:TCM non-drug measures combined with prone positioning can effectively treat patients with severe COVID-19.The combined therapy significantly increased SpO_(2)and improved symptom scores compared to prone positioning alone,thus improving the patients'respiratory function to help them recover.However,the improvement rate did not differ between the two groups.展开更多
Objective:This trial is aimed at evaluating the efficacy and safety of acupuncture on treating FC.Methods:We describe the protocol for a randomized,patient-assessor-blinded,sham controlled trial.Seventy-two eligible p...Objective:This trial is aimed at evaluating the efficacy and safety of acupuncture on treating FC.Methods:We describe the protocol for a randomized,patient-assessor-blinded,sham controlled trial.Seventy-two eligible patients will be randomly assigned to the intervention group(acupuncture)or the control group(sham acupuncture).All treatment will be given 26 sessions of acupuncture or sham acupuncture over 8 weeks(5 times per week in the first 2 weeks,3 times per week during weeks 3-6,and 2 times per week during weeks 7 and 8).Each treatment will last for 20 min.The primary outcome is the change in mean complete spontaneous bowel movements(CSBMs)per week.The secondary out?comes are patient assessment of constipation quality of life questionnaire(PAC-QOL),self-rating anxiety scale(SAS),and the dosage of the medication.All adverse events will be recorded in detail and managed by corresponding researchers as quickly as possible.Outcomes will be evaluated at baseline(1 week before treatment),2 weeks after intervention begins,6 weeks after intervention begins,8 weeks after intervention begins,4 weeks follow-up,and 12 weeks follow-up.Discussion:The results of this study will provide the evidence of the efficacy and safety of acupuncture as a traditional treatment methods for functional constipation.Trial registration:Chinese Clinical Trial Registry,ChiCTR-INR-17011472.Registered on 23 May 2017.展开更多
Background:Hot flashes are one of the most common symptoms in menopause and significantly affect the quality of life of 67% of menopausal women.Acupuncture is found to be a low risk treatment in treating hot flashes b...Background:Hot flashes are one of the most common symptoms in menopause and significantly affect the quality of life of 67% of menopausal women.Acupuncture is found to be a low risk treatment in treating hot flashes but the evidence for its effectiveness is inconclusive.We developed an optimized acupuncture treatment protocol and designed a randomized controlled trial(RCT) to assess the efficacy of acupuncture for reducing hot flashes in menopausal women.Methods:This is a single-site,single-blind,randomized sham-controlled trial with two parallel arms.A total of 60 eligible patients will be recruited and randomly assigned to either the acupuncture group(n=30) or the sham acupuncture group(n=30).Treatment will be given twice a week,for 30 min,for six consecutive weeks.The primary outcome is the hot flashes scores,assessed using the validated hot flashes diary at baseline,week 3,week 6 and week 10.The secondary outcome will be measured by menopause-specific quality of life(MENQOL) at baseline,week 6,and week 10.Meanwhile,any adverse events will be recorded.Discussion:If the outcome of this study confirms acupuncture to be an effective therapy to reduce hot flashes in menopausal women,we expect this study to inspire further investigations and provide useful information in forming an optimal acupuncture treatment protocol for clinic.Trial registration:Chinese Clinical Trial Registry identifier:ChiCTR1800018638,Date of registration:30 th September 2018.URL:http://www.chictr.org.cn/showproj.aspx?proj=31462.展开更多
The synchronized development of mineralized bone and blood vessels is a fundamental requirement for successful bone tissue regeneration.Adequate energy production forms the cornerstone supporting new bone formation.ET...The synchronized development of mineralized bone and blood vessels is a fundamental requirement for successful bone tissue regeneration.Adequate energy production forms the cornerstone supporting new bone formation.ETS variant 2(ETV2)has been identified as a transcription factor that promotes energy metabolism reprogramming and facilitates the coordination between osteogenesis and angiogenesis.In vitro molecular experiments have demonstrated that ETV2 enhances osteogenic differentiation of dental pulp stem cells(DPSCs)by regulating the ETV2-prolyl hydroxylase 2(PHD2)-hypoxia-inducible factor-1α(HIF-1α)-vascular endothelial growth factor A(VEGFA)axis.Notably,ETV2 achieves the rapid reprogramming of energy metabolism by simultaneously accelerating mitochondrial aerobic respiration and glycolysis,thus fulfilling the energy requirements essential to expedite osteogenic differentiation.Furthermore,decreasedα-ketoglutarate release from ETV2-modified DPSCs contributes to microcirculation reconstruction.Additionally,we engineered hydroxyapatite/chitosan microspheres(HA/CS MS)with biomimetic nanostructures to facilitate multiple ETV2-DPSC functions and further enhanced the osteogenic differentiation.Animal experiments have validated the synergistic effect of ETV2-modified DPSCs and HA/CS MS in promoting the critical-size bone defect regeneration.In summary,this study offers a novel treatment approach for vascularized bone tissue regeneration that relies on energy metabolism activation and the maintenance of a stable local hypoxia signaling state.展开更多
基金supported by National Natural Science Foundation of China(No.82104986 and 82274643)Shanghai“Rising Stars of Medical Talents”Youth Development Program(No.SHWSRS[2023]_062)from Shanghai Municipal Health Commission。
文摘Objective:Comorbid pain and depression are common but remain difficult to treat.Electroacupuncture(EA)can effectively improve symptoms of depression and relieve pain,but its neural mechanism remains unclear.Therefore,we used resting-state functional magnetic resonance imaging(rs-fMRI)to detect cerebral changes after initiating a mouse pain model via constriction of the infraorbital nerve(CION)and then treating these animals with EA.Methods:Forty male C57BL/6J mice were divided into 4 groups:control,CION model,EA,and sham acupuncture(without needle insertion).EA was performed on the acupoints Baihui(GV20)and Zusanli(ST36)for 20 min,once a day for 10 consecutive days.The mechanical withdrawal threshold was tested3 days after the surgery and every 3 days after the intervention.The depressive behavior was evaluated with the tail suspension test,open-field test,elevated plus maze(EPM),sucrose preference test,and marble burying test.The rs-fMRI was used to detect the cerebral changes of the functional connectivity(FC)in the mice following EA treatment.Results:Compared with the CION group,the mechanical withdrawal threshold increased in the EA group at the end of the intervention(P<0.05);the immobility time in tail suspension test decreased(P<0.05);and the times of the open arm entry and the open arm time in the EPM increased(both P<0.001).There was no difference in the sucrose preference or marble burying tests(both P>0.05).The fMRI results showed that EA treatment downregulated the amplitude of low-frequency fluctuations and regional homogeneity values,while these indicators were elevated in brain regions including the amygdala,hippocampus and cerebral cortex in the CION model for comorbid pain and depression.Selecting the amygdala as the seed region,we found that the FC was higher in the CION group than in the control group.Meanwhile,EA treatment was able to decrease the FC between the amygdala and other brain regions including the caudate putamen,thalamus,and parts of the cerebral cortex.Conclusion:EA can downregulate the abnormal activation of neurons in the amygdala and improve its FC with other brain regions,thus exerting analgesic and antidepressant effects.Please cite this article as:Yin X,Zeng XL,Lin JJ,Xu WQ,Cui KY,Guo XT,Li W,Xu SF.Brain functional changes following electroacupuncture in a mouse model of comorbid pain and depression:A restingstate functional magnetic resonance imaging study.
基金Supported by grants from Shanghai Municipal Health Commission for the Inheritance and Innovation of Traditional Chinese Medicine:ZY (2021-2023)-0204。
文摘Background Acupuncture and its related therapies,as an important part of traditional Chinese medicine,have been widely accepted by the public and healthcare professionals all over the world.According to previous reviews,the department of acupuncture is a potential place where nosocomial infection might occur.Objectives To investigate the common pathogens and possible risk factors for nosocomial infection,figure out the measures and strategies for control and prevention,and provide general reporting guideline for future cases.Methods A systematic literature search of 6 libraries(EMBASE,CINAHL,PubMed,VIP,CNKI,SinoMed)was carried out on nosocomial infection(NIs)after acupuncture and its related therapies(e.g.,moxibustion,cupping,massage,dry needling)published from January 1,2012 to August 31,2023.Studies providing primary data were included;reviews,comments,and non-primary data studies were excluded to prevent duplicate case analysis.Data on bibliographic details,study characteristics,and clinical information were extracted.Results were synthesized through tabulation and categorized by therapy type,country income level,symptoms/diagnoses,pathogens,risk factors,treatments,and outcomes.Conclusion Nosocomial infections after acupuncture and its related therapies are possible but preventable.Prevention measures can be carried out in terms of the risk factors listed above.Future case reports are suggested to provide specific details of infection,including the setting,qualification,treatment,disinfection,and causal evidence.
基金supported by grant from Shanghai Municipal Health Commission,China (No. 2018MSB-12). The sponsor provided financial support in the case observation,the collection,analysis of data,and the decision to submit the article for publication。
文摘Background:Hemorrhoids are one of the most common conditions that lead to surgery,and until now surgical hemorrhoidectomy has been the major effective treatment.Post-operative pain from hemorrhoidectomy has been experienced by thousands of patients and remains a major inconvenience of the operation.Objective:This study evaluates the clinical efficacy of the pestle needle therapy,an acupoint stimulation method,for relief of post-hemorrhoidectomy pain.Design,setting,participants and interventions:This was a single-center,patient-assessor-blinded and randomized controlled trial with 154 patients receiving Milligan hemorrhoidectomy surgery.Eligible patients were randomly assigned to either a treatment group or a control group at a ratio of 1:1.The treatment group received the pestle needle therapy,with manual stimulation at Yaoshu(DU2),Mingmen(DU4),Changqiang(DU1),Chengshan(BL57),Erbai(EX-UE2)and the perianal points(1,3,5,7,9,and 11 o’clock around the lesion);while the control group received a sham treatment with very light pressure.Three sessions of treatment were performed at 30 min,4 h and 12 h after the surgery,and each lasted for 15 min.Main outcome measures:The primary outcome was post-operative pain measured with the visual analogue scale(VAS)at 12 h after surgery.The secondary outcomes included the VAS scores measured at0.5,2,4,6,8,24 and 48 h after surgery,the analgesic dose,the time and the VAS score of the patients’first defecation after surgery,as well as the Hamilton Rating Scale for Anxiety(HAMA)evaluated before discharge.Results:The mean pain score of the treatment group was significantly lower than that of the control group(3.10±1.27 vs 4.82±1.29;P<0.001)at 12 h after surgery.Compared with the control group,patients in the treatment group needed a smaller dose of analgesic within the first 24 hours after surgery(P=0.002);and their HAMA scores before discharge were lower(4.07±2.40 vs 5.10±2.45,P=0.009).Compared to the treatment group,patients in the control group had a greater time to the first defecation after surgery([52.34±15.72]h vs[27.08±13.68]h;P<0.001),but there was no difference in their VAS scores at the first defecation(P=0.092).Conclusion:The pestle needle therapy was effective for relieving pain,reducing anxiety and improving bowel function after hemorrhoidectomy,and it is worthy of clinical application.
基金funded by the Construction Program of Demonstration Centers for TCM Non-Drug Therapyfrom Shanghai Municipal Health Commission(No.ZY[2021-2023]-0204)。
文摘Background:The outbreak of coronavirus disease 2019(COVID-19)infection posed a huge threat and burden to public healthcare in late 2022.Non-drug measures of traditional Chinese medicine(TCM),such as acupuncture,cupping and moxibustion,are commonly used as adjuncts in China to help in severe cases,but their effects remain unclear.Objectives:To observe the clinical effect of TCM non-drug measures in improving respiratory function and symptoms among patients with severe COVID-19.Design,setting,participants and interventions:This study was designed as a multicenter,assessor-blind,randomized controlled trial.Hospitalized patients with COVID-19 were randomly assigned to the treatment or control group.The treatment group received individualized TCM non-drug measures in combination with prone position ventilation,while the control group received prone position ventilation only for 5 consecutive days.Main outcome measures:The primary outcome measures were the percentage of patients with improved oxygen saturation(SpO_(2))at the end of the 5-day intervention,as well as changes of patients'respiratory rates.The secondary outcome measures included changes in SpO_(2)and total score on the self-made respiratory symptom scale.The improvement rate,defined as a 3-day consecutive increase in SpO_(2),the duration of prone positioning,and adverse events were recorded as well.Results:Among the 198 patients included in the intention-to-treat analysis,159(80.3%)completed all assessments on day 5,and 39(19.7%)patients withdrew from the study.At the end of the intervention,71(91%)patients in the treatment group had SpO_(2)above 93%,while 61(75.3%)in the control group reached this level.The proportion of participant with improved SpO_(2)was significantly greater in the intervention group(mean difference[MD]=15.7;95%confidence interval[CI]:4.4,27.1;P=0.008).Compared to the baseline,with daily treatment there were significant daily decreases in respiratory rates in both groups,but no statistical differences between groups were found(all P≥0.05).Compared to the control group,the respiratory-related symptoms score was lower among patients in the treatment group(MD=-1.7;95%CI:-2.8,-0.5;P=0.008)after day 3 of treatment.A gradual decrease in the total scores of both groups was also observed.Thirty-one adverse events occurred during the intervention,and 2patients were transferred to the intensive care unit due to deterioration of their illness.Conclusion:TCM non-drug measures combined with prone positioning can effectively treat patients with severe COVID-19.The combined therapy significantly increased SpO_(2)and improved symptom scores compared to prone positioning alone,thus improving the patients'respiratory function to help them recover.However,the improvement rate did not differ between the two groups.
基金supported by the Shanghai Municipal Commission of Health and Family Planning(Grant No.2016LQ015)
文摘Objective:This trial is aimed at evaluating the efficacy and safety of acupuncture on treating FC.Methods:We describe the protocol for a randomized,patient-assessor-blinded,sham controlled trial.Seventy-two eligible patients will be randomly assigned to the intervention group(acupuncture)or the control group(sham acupuncture).All treatment will be given 26 sessions of acupuncture or sham acupuncture over 8 weeks(5 times per week in the first 2 weeks,3 times per week during weeks 3-6,and 2 times per week during weeks 7 and 8).Each treatment will last for 20 min.The primary outcome is the change in mean complete spontaneous bowel movements(CSBMs)per week.The secondary out?comes are patient assessment of constipation quality of life questionnaire(PAC-QOL),self-rating anxiety scale(SAS),and the dosage of the medication.All adverse events will be recorded in detail and managed by corresponding researchers as quickly as possible.Outcomes will be evaluated at baseline(1 week before treatment),2 weeks after intervention begins,6 weeks after intervention begins,8 weeks after intervention begins,4 weeks follow-up,and 12 weeks follow-up.Discussion:The results of this study will provide the evidence of the efficacy and safety of acupuncture as a traditional treatment methods for functional constipation.Trial registration:Chinese Clinical Trial Registry,ChiCTR-INR-17011472.Registered on 23 May 2017.
基金Supported by grants from Shanghai Municipal Commission of Health and Family Planning:ZY(2018-2020)-ZYJS-03。
文摘Background:Hot flashes are one of the most common symptoms in menopause and significantly affect the quality of life of 67% of menopausal women.Acupuncture is found to be a low risk treatment in treating hot flashes but the evidence for its effectiveness is inconclusive.We developed an optimized acupuncture treatment protocol and designed a randomized controlled trial(RCT) to assess the efficacy of acupuncture for reducing hot flashes in menopausal women.Methods:This is a single-site,single-blind,randomized sham-controlled trial with two parallel arms.A total of 60 eligible patients will be recruited and randomly assigned to either the acupuncture group(n=30) or the sham acupuncture group(n=30).Treatment will be given twice a week,for 30 min,for six consecutive weeks.The primary outcome is the hot flashes scores,assessed using the validated hot flashes diary at baseline,week 3,week 6 and week 10.The secondary outcome will be measured by menopause-specific quality of life(MENQOL) at baseline,week 6,and week 10.Meanwhile,any adverse events will be recorded.Discussion:If the outcome of this study confirms acupuncture to be an effective therapy to reduce hot flashes in menopausal women,we expect this study to inspire further investigations and provide useful information in forming an optimal acupuncture treatment protocol for clinic.Trial registration:Chinese Clinical Trial Registry identifier:ChiCTR1800018638,Date of registration:30 th September 2018.URL:http://www.chictr.org.cn/showproj.aspx?proj=31462.
基金supported by the National Natural Science Foundation of China (grants 82301039)the Natural Science Foundation of the Anhui Higher Education Institutions of China (grant 2022AH050758)+2 种基金Anhui Institute of Translational Medicine,Natural Sciences (grant 2022zhyx-C87)National Natural Science Foundation of China (82170951)Beijing Municipal Natural Science Foundation (7222079).
文摘The synchronized development of mineralized bone and blood vessels is a fundamental requirement for successful bone tissue regeneration.Adequate energy production forms the cornerstone supporting new bone formation.ETS variant 2(ETV2)has been identified as a transcription factor that promotes energy metabolism reprogramming and facilitates the coordination between osteogenesis and angiogenesis.In vitro molecular experiments have demonstrated that ETV2 enhances osteogenic differentiation of dental pulp stem cells(DPSCs)by regulating the ETV2-prolyl hydroxylase 2(PHD2)-hypoxia-inducible factor-1α(HIF-1α)-vascular endothelial growth factor A(VEGFA)axis.Notably,ETV2 achieves the rapid reprogramming of energy metabolism by simultaneously accelerating mitochondrial aerobic respiration and glycolysis,thus fulfilling the energy requirements essential to expedite osteogenic differentiation.Furthermore,decreasedα-ketoglutarate release from ETV2-modified DPSCs contributes to microcirculation reconstruction.Additionally,we engineered hydroxyapatite/chitosan microspheres(HA/CS MS)with biomimetic nanostructures to facilitate multiple ETV2-DPSC functions and further enhanced the osteogenic differentiation.Animal experiments have validated the synergistic effect of ETV2-modified DPSCs and HA/CS MS in promoting the critical-size bone defect regeneration.In summary,this study offers a novel treatment approach for vascularized bone tissue regeneration that relies on energy metabolism activation and the maintenance of a stable local hypoxia signaling state.
