ETV2 regulating PHD2-HIF-1αaxis controls metabolism reprogramming promotes vascularized bone regeneration

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.

Effects of the pestle needle therapy,a type of acupoint stimulation,on post-hemorrhoidectomy pain:A randomized controlled trial

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.

Efficacy and safety of acupuncture on the treatment of functional constipation: Study protocol for a randomized controlled trial

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.

Effect of acupuncture on menopausal hot flashes:Study protocol for a randomized controlled clinical trial

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.