Influence of electroacupuncture on ghrelin and the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthase signaling pathway in spontaneously hypertensive rats / 中西医结合学报

OBJECTIVE@#To investigate the influence of electroacupuncture (EA) on ghrelin and the phosphoinositide 3-kinase/protein kinase B/endothelial nitric oxide synthase (PI3K/Akt/eNOS) signaling pathway in spontaneously hypertensive rats (SHRs).@*METHODS@#Eight Wistar-Kyoto rats were used as the healthy blood pressure (BP) control (normal group), and 32 SHRs were randomized into model group, EA group, EA plus ghrelin group (EA + G group), and EA plus PF04628935 group (a potent ghrelin receptor blocker; EA + P group) using a random number table. Rats in the normal group and model group did not receive treatment, but were immobilized for 20 min per day, 5 times a week, for 4 continuous weeks. SHRs in the EA group, EA + G group and EA + P group were immobilized and given EA treatment in 20 min sessions, 5 times per week, for 4 weeks. Additionally, 1 h before EA, SHRs in the EA + G group and EA + P group were intraperitoneally injected with ghrelin or PF04628935, respectively, for 4 weeks. The tail-cuff method was used to measure BP. After the 4-week intervention, the rats were sacrificed by cervical dislocation, and pathological morphology of the abdominal aorta was observed using hematoxylin-eosin (HE) staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of ghrelin, nitric oxide (NO), endothelin-1 (ET-1) and thromboxane A2 (TXA2) in the serum. Isolated thoracic aortic ring experiment was performed to evaluate vasorelaxation. Western blot was used to measure the expression of PI3K, Akt, phosphorylated Akt (p-Akt) and eNOS proteins in the abdominal aorta. Further, quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to measure the relative levels of mRNA expression for PI3K, Akt and eNOS in the abdominal aorta.@*RESULTS@#EA significantly reduced the systolic BP (SBP) and diastolic BP (DBP) (P < 0.05). HE staining showed that EA improved the morphology of the vascular endothelium to some extent. Results of ELISA indicated that higher concentrations of ghrelin and NO, and lower concentrations of ET-1 and TXA2 were presented in the EA group (P < 0.05). The isolated thoracic aortic ring experiment demonstrated that the vasodilation capacity of the thoracic aorta increased in the EA group. Results of Western blot and qRT-PCR showed that EA increased the abundance of PI3K, p-Akt/Akt and eNOS proteins, as well as expression levels of PI3K, Akt and eNOS mRNAs (P < 0.05). In the EA + G group, SBP and DBP decreased (P < 0.05), ghrelin concentrations increased (P < 0.05), and the concentrations of ET-1 and TXA2 decreased (P < 0.05), relative to the EA group. In addition, the levels of PI3K and eNOS proteins, the p-Akt/Akt ratio, and the expression of PI3K, Akt and eNOS mRNAs increased significantly in the EA + G group (P < 0.05), while PF04628935 reversed these effects.@*CONCLUSION@#EA effectively reduced BP and protected the vascular endothelium, and these effects may be linked to promoting the release of ghrelin and activation of the PI3K/Akt/eNOS signaling pathway.

Electroacupuncture Attenuated Phenotype Transformation of Vascular Smooth Muscle Cells via PI3K/Akt and MAPK Signaling Pathways in Spontaneous Hypertensive Rats / 中国结合医学杂志

OBJECTIVE@#To investigate whether the antihypertensive mechanism of electroacupuncture (EA) is associated with attenuating phenotype transformation of vascular smooth muscle cells (VSMCs) via phosphoinositide3-kinase (PI3K)/protein kinase B (Akt) and mitogen-activated protein kinase (MAPK) signaling pathways.@*METHODS@#Eight Wistar-ktoyo (WKY) rats were set as normal blood pressure group (normal group). A total of 32 spontaneous hypertensive rats (SHRs) were randomly divided into 4 groups using random number tables: a model group, an EA group, an EA+PI3K antagonist group (EA+P group), and an EA+p38 MAPK agonist+extracellular signal-regulated kinase (ERK) agonist group (EA+M group) (n=8/group). SHRs in EA group, EA+P group and EA+M group received EA treatment 5 sessions per week for continuous 4 weeks, while rats in the normal and model groups were bundled in same condition. The systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) of each rat was measured at 0 week and the 4th week. After 4-week intervention, thoracic aorta was collected for hematoxylin-eosin (HE) staining, immunohistochemistry [the contractile markers α-smooth muscle actin (α-SMA) and calponin and the synthetic marker osteopontin (OPN)] and Western blot [α-SMA, calponin, OPN, PI3K, phosphorylated-Akt (p-Akt), Akt, p-p42/44 ERK, total p42/44 ERK, p-p38 MAPK and total p38 MAPK].@*RESULTS@#EA significantly reduced SBP, DBP and MAP (P<0.01). HE staining showed that the wall thickness of thoracic aorta in EA group was significantly decreased (P<0.01). From results of immunohistochemistry and Western blot, EA increased the expression of α-SMA and calponin, and decreased the expression of OPN (P<0.01). In addition, the expression of PI3K and p-Akt increased (P<0.01), while the expression of p-p42/44 ERK and p-p38 MAPK decreased in EA group (P<0.01). However, these effects were reversed by PI3K antagonist, p38 MAPK agonist and ERK agonist.@*CONCLUSIONS@#EA was an effective treatment for BP management. The antihypertensive effect of EA may be related with inhibition of phenotypic transformation of VSMCs, in which the activation of PI3K/Akt and the repression of MAPK pathway were involved.

Efficacy and Safety of Cladribine-based Intensified Conditioning Regimen in Hematopoietic Stem Cell Transplantation in Patients with High-Risk Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy, safety and the risk factors affecting prognosis of high-risk acute myeloid leukemia (AML) patients treated by cladribine-based intensified conditioning regimen.@*METHODS@#The clinical data of 28 patients with high-risk AML treated by cladribine in combination with busulfan plus cyclophosphamide (BuCy) intensified conditioning regimen before allogeneic hematopoietic stem cell transplantation (allo-HSCT) in Zhujiang Hospital, Southern Medical University from October 2016 to June 2020 were analyzed retrospectively. The overall survival (OS) rate, cumulative progression-free survival (PFS) rate, relapse rate, non-relapse mortality (NRM), regimen related toxicity (RRT) and risk factors affecting prognosis of the patients were analyzed.@*RESULTS@#The 1-year OS and PFS of the patients after implantation was (78.8±8.6)% and (79.8±8.1)%, while the 1-year cumulative relapse rate and NRM of the patients was 9.3% and 22.0%, respectively. The 1-year expected OS of MRD- high-risk patients before HSCT was 100%. The 1-year expected OS and PFS of the patients in pre-transplant relapse group was (46.9±18.7)% and (50.0±17.7)%, respectively. The incidence of I/II grade RRT was 39.3%. NO III/IV grade RRT were found in 28 patients. Multivariate analysis showed that pre-transplant relapse was the independent risk factor affecting OS and PFS of the patients.@*CONCLUSION@#The intensified conditioning regimen of cladribine in combination with BuCy can reduce the relapse rate of high-risk AML transplantation, and its RRT is mild, exhibiting good safety. MRD- high-risk patients before HSCT can achieve better transplant benefits, but the prognosis of patients with relapse before transplantation is not significantly improved. Therefore, for non-relapsed high-risk AML patients, this intensified conditioning regimen deserves to be considered.

Efficacy and Prognosis of Allogeneic Hematopoietic Stem Cell Transplantation for Acute Monocytic Leukemia Patients / 中国实验血液学杂志

OBJECTIVE@#To investigate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of acute monocytic leukemia (AML-M5) and the related factors that affecting the prognosis of the patients.@*METHODS@#The clinical data of 71 patients with AML-M5 treated with allo-HSCT in Zhujiang Hospital Affiliated to Southern Medical University from April 2009 to October 2019 were collected and retrospectively analyzed. The incidence of graft-versus-host disease (GVHD), cumulative overall survival (OS) rate, cumulative progression-free survival (PFS) rate, transplantation-related mortality (TRM), relapse rate and the risk factors affecting prognosis in the patients were analyzed.@*RESULTS@#66 patients obtained hematopoietic reconstruction after transplantation, the median time of granulocyte implantation was 12 (9-26) d, and the median time of megakaryocytic implantation was 13 (8-72) d. The incidence of acute GVHD and chronic GVHD was 33.8% (24/71) and 36.6% (26/71), respectively. The median follow-up time was 13.81 (0.16 to 112.54) months; the median OS and PFS was 31.27 and 26.07 months, respectively. The cumulative OS of the patients in 1 and 3 years after transplantation was 64.9% and 48.6%, respectively, and the cumulative PFS of the patients in 1 and 3 years was 55.0% and 39.5%, respectively. The cumulative relapse rate of the patients in 1 and 3 years was 24% and 40%, respectively. Multivariate analysis showed that pre-transplantation relapse was the independent risk factor affecting OS (HR=2.32, 95%CI:1.17-4.62, P=0.02) and PFS (HR=3.08, 95%CI:1.61-5.90, P=0.001) of the patients; invasive fungal disease after transplantation was the independent risk factor affecting OS (HR=2.71, 95% CI:1.32-5.56, P=0.007) and PFS (HR=2.87, 95%CI=1.40-5.86, P=0.004) of the patients; FLT3 mutation was the independent risk factor affecting PFS (HR=2.13, 95%CI=1.07-4.24, P=0.03) of the patients.@*CONCLUSION@#AML-M5 is the intermediate or high-risk leukemia, and allo-HSCT can improve the survival prognosis of the patients. Pre-transplantation relapse and invasive fungal disease after transplantation are the important factors affecting the efficacy of allo-HSCT in patients with AML-M5.

Researches of Mirror Therapy in Recent 20 Years: A Visualization Analysis Using CiteSpace / 中国康复理论与实践

Objective:To analyze the current status and hotspots of mirror therapy in recent 20 years. Methods:The literatures about mirror therapy in science citation index expanded (SCI-E) of Web of Science (WOS) from 1998 to 2019 were researched. CiteSpace was used to map the cooperative network of authors, countries and research institutions of relevant literatures; the keywords were taken as nodes for co-occurrence analysis and conduct clustering analysis, time evolution analysis and Burst analysis; the cited literatures and cited journals were taken as nodes to draw co-cited maps. In addition, the cited literatures were dealt with Burst analysis. Results:Totally, 435 articles were included. The high yield authors were Mosaley G L and Tsao J W. The high yield countries were the United States, Germany and England. The high yield institutions were Heidelberg University and University of South Australia. Prediction of phantom limb pain, complex regional pain syndrome, the improvement of motor function especially upper limb function, and augmented reality after stroke will be the focus of mirror therapy in the future. Conclusion:The research of mirror therapy is still in its infancy, with rapid development but insufficient influence.