Objective To investigate in vitro possible mechanisms by which low frequency electrical stimulation may stimulate peripheral blood stem cells' proliferation and differentiation into Schwann cells (SCs).Methods The original generation of peripheral blood stem cells was cultured using Sprague-Dawley (SD) rats.The third passage stem cells were divided into a low frequency stimulation group,an extracellular signal-regulated kinase (ERK) group,a combination group and a control group.All 4 groups were cultured in DMEM containing 2％ fetal bovine serum by adding the SC supernatant.The low frequency electrical stimulation group was given 1 h of continuous low frequency stimulation.For the ERK group 50 mmol/L of the inhibitor PD98059 was added.The combination group was given the inhibitor plus 1h of sustained low frequency electrical stimulation.The control group received no special intervention.Before and after induction the 3-(4,5-dimethyl-thiazol-2)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to detect the absorbance value A of 4 cells at 570 nm (A750),and after induction Western blotting was used to determine cyclin D1 (cyclin D1) and cyclin-dependent kinases (CDK4).Results Before the intervention peripheral blood stem cells in each group had no significant differences in their A750 values.After the intervention,the A750 values of the low frequency electrical stimulation,the ERK group,the combination group and the control group were (1.051 ±0.058),(0.363 ±0.343),(0.894 ±0.343) and (0.758 ±0.047),respectively.This showed a statistically significant increase for all groups except the ERK group.The differences among the groups were also statistically significant.The expression of S-100,glial fibrillary acidic protein (GFAP) and P75 was highest in the low frequency electrical stimulation group,and in the ERK group they were the lowest.S-100,GFAP and P75 protein expression also was highest in the low frequency electrical stimulation group and lowest in the ERK group,and the inter-group differences were statistically significant.ERK expression showed no significant difference among the groups.Compared with the control group,the expression of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2),cyclin D1 and CDK4 protein in the low frequency electrical stimulation group and the combination group were all significantly higher and the protein expression in the ERK group was significantly lower.The p-ERK1/2,cyclin D1 and CDK4 protein levels in the combination group were significantly lower than in the low frequency electrical stimulation group and higher than in the ERK group.Conclusions Low frequency electrical stimulation can promote peripheral blood stem cell proliferation and induce cell differentiation into Schwann cells,at least in vitro.The ERK signaling pathways are part of the signaling pathways of the proliferation and differentiation.

【Objective】 To evaluate the clinical efficacy and safety of platelet-rich plasma(PRP) in acute achilles tendon injury by meta-analysis. 【Methods】 Literature on clinical randomized controlled trial of PRP in the treatment of acute achilles tendon injury from Wanfang database, CNKI, VIP database, The Chinese Biological Literature Database, The Chinese Clinical Trials Registry, PubMed, Embase, Cochrane and The US Clinical Trials Registry as of August 2023 were retrieved. The control group received conventional treatment for acute achilles tendon injury, while PRP treatment group received additional PRP treatment. The primary outcome measure was visual analogue pain scale, and the secondary outcome measures were the achilles tendon fracture score, maximum heel rise height, calf circumference and ankle range of motion. The quality of the literature was assessed using the Cochrane manual, and a meta-analysis of qualified literature was performed using RevMan 5.3 software. 【Results】 Seven articles were finally included, involving 421 patients with acute achilles tendon injury, including 212 patients in the PRP treatment group, and 209 patients in the conventional treatment group. The results of meta-analysis showed that there was no difference between the conventional treatment group and the PRP treatment group in terms of the visual analogue pain scale(SMD=-0.44, 95%CI: -0.94~0.06, P>0.05), calf circumference (MD=1.14, 95% CI: -1.56-3.84, P>0.05), ankle joint toe flexion range of motion (SMD=1.85, 95%CI: -1.38-5.09, P>0.05), ankle dorsiflexion range of motion(SMD=2.61, 95%CI: -0.95-6.17, P>0.05), achilles tendon fracture score (MD=-5.60, 95%CI: -15.36-4.16, P>0.05) and the maximum heel rise height (MD=-2.48, 95%CI: -5.30-0.33, P>0.05). And there was no difference in the incidence of adverse reactions between the two groups (X²=2. 455, P>0.05). 【Conclusion】 PRP injection for acute achilles tendon injury does not improve the biomechanical and clinical outcomes of patients, and the use of PRP does not increase the occurrence of adverse reactions.

Objective To investigate whether activation of mitochondrial acetal dehydrogenase 2(ALDH2)alleviates hypoxic pulmonary hypertension by regulating the SIRT1/PGC-1α signaling pathway.Methods Thirty 8-week-old C57 BL/6 mice were randomized into control,hypoxia,and hypoxia+Alda-1(an ALDH2 activator)group(n=10),and the mice in the latter two groups,along with 10 ALDH2 knockout(ALDH2-/-)mice,were exposed to hypoxia(10%O2,90%N2)with or without daily intraperitoneal injection of Alda-1 for 4 weeks.The changes in right ventricular function and pressure(RVSP)of the mice were evaluated by echocardiography and right ventricular catheter test,and pulmonary artery pressure was estimated based on RVSP.Pulmonary vascular remodeling,right ventricular injury,myocardial α-SMA expression,distal pulmonary arteriole muscle normalization,right ventricular cross-sectional area,myocardial cell hypertrophy,and right cardiac hypertrophy index were assessed with HE staining,immunofluorescence staining and WGA staining,and the expressions of ALDH2,SIRT1,PGC-1α,P16INK4A and P21CIP1 were detected.In pulmonary artery smooth muscle cells with hypoxic exposure,the effect of Alda-1 and EX527 on cell senescence and protein expressions was evaluated using β-galactose staining and Western blotting.Results The wild-type mice with hypoxic exposure showed significantly increased RVSP,right ventricular free wall thickness and myocardial expressions of P16INK4A and P21CIP1,which were effectively lowered by treatment with Alda-1 but further increased in ALDH2-/-mice.In cultured pulmonary artery smooth muscle cells,hypoxic exposure significantly increased senescent cell percentage and cellular expressions of P16INK4A and P21CIP1,which were all lowered by treatment with Alda-1,but its effect was obviously attenuated by EX527 treatment.Conclusion ALDH2 alleviates hypoxia-induced senescence of pulmonary artery smooth muscle cells by upregulating the SIRT1/PGC-1α signaling pathway to alleviate pulmonary hypertension in mice.

Objective To investigate whether activation of mitochondrial acetal dehydrogenase 2(ALDH2)alleviates hypoxic pulmonary hypertension by regulating the SIRT1/PGC-1α signaling pathway.Methods Thirty 8-week-old C57 BL/6 mice were randomized into control,hypoxia,and hypoxia+Alda-1(an ALDH2 activator)group(n=10),and the mice in the latter two groups,along with 10 ALDH2 knockout(ALDH2-/-)mice,were exposed to hypoxia(10%O2,90%N2)with or without daily intraperitoneal injection of Alda-1 for 4 weeks.The changes in right ventricular function and pressure(RVSP)of the mice were evaluated by echocardiography and right ventricular catheter test,and pulmonary artery pressure was estimated based on RVSP.Pulmonary vascular remodeling,right ventricular injury,myocardial α-SMA expression,distal pulmonary arteriole muscle normalization,right ventricular cross-sectional area,myocardial cell hypertrophy,and right cardiac hypertrophy index were assessed with HE staining,immunofluorescence staining and WGA staining,and the expressions of ALDH2,SIRT1,PGC-1α,P16INK4A and P21CIP1 were detected.In pulmonary artery smooth muscle cells with hypoxic exposure,the effect of Alda-1 and EX527 on cell senescence and protein expressions was evaluated using β-galactose staining and Western blotting.Results The wild-type mice with hypoxic exposure showed significantly increased RVSP,right ventricular free wall thickness and myocardial expressions of P16INK4A and P21CIP1,which were effectively lowered by treatment with Alda-1 but further increased in ALDH2-/-mice.In cultured pulmonary artery smooth muscle cells,hypoxic exposure significantly increased senescent cell percentage and cellular expressions of P16INK4A and P21CIP1,which were all lowered by treatment with Alda-1,but its effect was obviously attenuated by EX527 treatment.Conclusion ALDH2 alleviates hypoxia-induced senescence of pulmonary artery smooth muscle cells by upregulating the SIRT1/PGC-1α signaling pathway to alleviate pulmonary hypertension in mice.