BACKGROUND: Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI. METHODS: In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy. RESULTS: A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro  studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent. CONCLUSION Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals ; Arsenic Trioxide ; Autophagy/physiology* ; Reperfusion Injury/prevention & control* ; Mice ; Male ; Proto-Oncogene Proteins c-akt/physiology* ; Arsenicals/therapeutic use* ; Oxides/therapeutic use* ; Liver/metabolism* ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Mice, Inbred C57BL

This article summarized the current status and challenges of manipulation therapy for musculoskeletal pain and its placebo effect in clinical trials, analyzing the impact of the placebo effect on the evaluation of therapeutic efficacy. The efficacy of different manual manipulation techniques remains uncertain, and the degree of blinding and patient expectations play a crucial role in efficacy assessment. The article suggested improving trial design through standardized placebo intervention design, comprehensive investigation of patient expectations and psychological states, rigorous training of practitioners, and optimized diagnostic and treatment scenarios and doctor-patient relationship, to ensure consistency between intervention and placebo groups. Specific measures include the application of the DITTO (Deconstruct, Identify, Take out, Think, Optimize) framework, the use of standardized questionnaire tools, and multi-center, large-sample randomized controlled trials to enhance the external validity and statistical power of research results, thereby providing more scientifically reliable evidence for clinical practice.

The Flash radiotherapy(Flash-RT),which is the key breakthrough in the basic field of radiotherapy technique,which is expected to cause a new major transformation in the field of radiotherapy.In this paper,we reviewed the latest research advances of the application and the mechanism exploration of Flash-RT in tumor treatment.Current studies have found that both the Flash-RT with electron beams and photon and the Flash-RT with proton can reduce injury of normal tissue than radiotherapy with conventional dose-rate,but the relevant mechanisms are not yet clearly understood,which includes but not limited to oxygen depletion,DNA damage,cellular senescence,apoptosis and immune response.The difference of Flash-RT injury between tumor tissue and normal tissue further reduces the limitations of radiotherapy,and reduces the adverse reaction and complication compared with conventional radiotherapy,which has wide application prospects.

OBJECTIVE： To investigate the effects of Danhong injection （DHI） on gene expression profile of acute myocardial infarction （AMI） model rats. METHODS： Male SD rats were randomly divided into sham operation group， model group and DHI group （0.76 mL/kg）， with 10 rats in each group. AMI model was established by ligation of left anterior descending coronary artery in model group and DHI group. After modeling， sham operation group and model group were given constant volume of normal saline intramuscularly， and DHI group was given relevant medicine intramuscularly， once a day， for consecutive 14 days. After last administration， myocardial tissue in the marginal zone of infarction was separated. The change of gene expression profile was detected by gene chip technique. Using fold-change of relative expression as index， differentially expressed microRNA （miRNA） were screened. On the basis of retrieving their corresponding genes， gene ontology （GO） and KEGG pathway enrichment analysis were carried out by using DAVID bioinformatics resource database and KEGG pathway database， respectively. TargetScan database was used to predict the target gene messenger RNA （mRNA） corresponding to differentially expressed miRNA. Cytoscape 3.6.1 software was used to construct and analyze the miRNA-mRNA network. Agilent GeneSpring GX v11.5 software was used to screen target genes and miRNA related to inflammation in the above networks. RESULTS： Compared with sham operation group， there were 22 differentially expressed miRNAs in model group， 5 up-regulated and 17 down-regulated. Compared with model group， there were 26 differentially expressed miRNAs in DHI group， and all of them were up-regulated. The differentially expressed miRNAs related to DHI therapy for AMI included rno-let-7a-5p， rno-let-7d-5p， rno-let-7f-5p， rno-miR-26b-5p， rno-miR-29b-3p， cel-miR-39-3p， cel-miR-39-5p， rno-miR-142-5p， rno-miR-191a-5p， rno-miR-409a-3p. Results of GO analysis and KEGG pathway enrichment analysis showed that differentially expressed miRNAs were mainly concentrated in membrane-bound organelles， cytoplasm， endometrial system and other cell components. The molecular functions such as protein binding and ion binding were exerted through biological processes such as anatomical structure development， multicellular tissue development and development process，which were mainly enriched in calcium signaling pathway， PPAR signaling pathway， VEGF signaling pathway， cell apoptosis， glycosylphosphatidylinositol anchored biosynthesis， valine， leucine and isoleucine degradation， etc. miRNA-mRNA network analysis showed that there were 25 target gene mRNAs corresponding to differentially expressed miRNA and 24 miRNAs related to it. There were 6 inflammation-related target genes （IL6， IL1b， TNF， TLR4， CRP， CXCL12） in this network， involving 19 differentially expressed miRNAs. CONCLUSIONS： The therapeutic effect of DHI on AMI may be related to regulating the expression of related miRNA， affecting signal transduction of calcium ion， PPAR and VEGF pathways， and regulating the secretion of inflammatory markers such as interleukin， chemokine and C-reactive protein.

Objective To study the curative efficacy and safety of single-unit umbilical cord blood transplantation (sUCBT) for malignant hematologic diseases,which is provided by China's public cord blood bank.Methods We retrospectively analyzed 409 cases of malignant hematologic diseases who accepted myeloablative single-unit unrelated donor UCBT without ATG at our center between May 2008 and December 2016.A comparative analysis was made on the total nuclear cells (TNC) of the umbilical cord blood before freezing and after thawing,the cells of CD34+,the recovery rate of cells and the clinical effect of UCBT.Result 409 units of umbilical cord blood used in UCBT respectively came from eight China's public cord blood banks.The average TNC of 409 units of umbilical cord blood before freezing and after the tubular recovery were respectively 18.5 × 108 and 16.34 × 108 (p =0.000).The average recovery rate of the tubular recovery was 88.5％,and there was significant difference among cord blood banks (P =0.000).The average TNC of umbilical cord blood before freezing and transfusion were respectively 18.5 × 108 and 15.86 × 108 (p =0.000).The average recovery rate of umbilical cord blood transfusion was 85.9％,with the difference being significant among cord blood banks (P =0.000).The average number of CD34+ cells before freezing and after the tubular recovery was 11.18 × 106and 8.68 × 106 (p =0.000).The average recovery rate of CD34+ cells after the tubular recovery was 80.75 ％,with the difference being significant among the cord blood banks (P =0.000).At 42nd day after UCBT,the cumulative incidence of neutrophil engraftment was 95.4％,and the median time of the engraftment was 17 days (11-38 days).The cumulative incidence of platelet engraftment at 120th day was 84.6％,and the median time of the engraftment was 36 days (14-93 days).The cumulative incidence of erythrocyte engraftment at 60th day was 92％,and the median time of engraftment was 22 days (9d-60 days).After the umbilical cord blood provided by each bank was used in UCBT,it got the difference in cumulative incidence of engraftment.The P values for cumulative incidence of neutrophil,platelet and erythrocyte engraftment were respectively 0.004,0.01 and 0.000 2,with the differences being statistically significant.At 100th day after UCBT,the cumulative incidence of Ⅱ-Ⅳ and Ⅲ-Ⅳ degrees of acute graft-versus-host disease (aGVHD) was respectively 28.63％ and 15.7％.After umbilical cord blood provided by each bank was used in UCBT,it got the difference in cumulative incidence of aGVHD.There was no significant difference between Ⅱ-Ⅳ and Ⅲ-Ⅳ degrees (P =0.809 and 0.68 respectively).At 3rd year after UCBT,the cumulative incidence of relapse was 15.89％.After umbilical cord blood provided by each bank was used in UCBT,there was no significant difference in the cumulative incidence of relapse (P =0.898).At 3rd year after UCBT,the overall survival (OS) rate and disease free survival (DFS) rate were respectively 66.7％ and 59％.After umbilical cord blood provided by each bank was used in UCBT,it got the difference in OS and DFS.There was no significant difference in OS and DFS (P =0.566 and 0.703 respectively).At 3rd year after sUCBT,the rate of graft-versus-host diseases/relapse-free survival (GRFS) was 54.3％.After umbilical cord blood provided by each bank was used in UCBT,there was no significant difference in the rate of GRFS (P =0.449).Conclusion The umbilical cord blood provided by China's public cord blood bank was used in UCBT.It has a high safety and good efficacy in treating malignant hematologic diseases.But it needs to set up the standardized and normalized quality-control system of umbilical cord blood for China's public cord blood bank.

Objective To investigate the association between Has‐miRNA‐149 polymorphism and susceptibility of digestive tract cancer .Methods A systematic search of Pubmed ,EMBASE and Web of Science ,CNKI ,Wanfang was conducted for relevant studies .The odds ratios(OR) and 95% confidence intervals(95% CI) calculated by Stata12 .0 software were used to assess the asso‐ciation between Has‐miRNA‐149 polymorphism and risk of digestive tract cancer .The Q test ,I2 value and funnel plot were conduc‐ted to examine heterogeneity and publication bias ,respectively .Results A total of thirteen eligible studies containing 4 424 cases and 5 290 controls were included in this Meta analysis .There were significant relationships between Hsa‐miRNA‐149 polymorphism and susceptibility of digestive tract cancer (Domina model CT+CC vs .TT ,OR=0 .915 ,95% CI:0 .840-0 .996 ,P=0 .040 ;Hetero‐zygous model CT vs .TT ,OR=0 .880 ,95% CI:0 .803 -0 .965 ,P=0 .007) .In the stratified analysis ,it was found that the risk of colorectal cancer decreased in patients carrying CC/CT genotypes(OR=0 .834 ,95% CI:0 .715-0 .972 ,P=0 .021) ,especially in A‐sians (CT+CC vs .TT ,OR=0 .894 ,95% CI:0 .818-0 .977 ,P=0 .013) ,while that was not found in the Caucasoids .Conclusion Has‐miRNA‐149 polymorphism is associated with the susceptibility of digestive tract cancer .The CC/CT genotypes may decrease the risk of digestive tract cancer ,especially in Asians .

Objective To investigate the clinical curative effect of Danhong injection and Tongxinluo capsule in treating patients with cerebral Infarction. Methods Eighty cerebral infarction patients of Neurology Department in Kailuan General Hospital Affiliated to Hebei United University were selected and randomly divided into control and treatment groups. Patients in the control group were received the based therapy,and patients in treatment group were received Danhong injection and Tongxinluo capsule besides the based therapy. The levels of homocysteine(Hcy),blood lipid,blood viscosity were measured at before treatment,the 14th day,1 month and 3 months after the treatment. All data were analyzed by SPSS13. 0. Results (1)The levels of Hcy,total cholesterol( TC),triglyceride( TG)and blood viscosity( high shear viscosity,low shear viscosity and hematocrit)in treatment group were significantly different from the control group at the 14th day after treatment(P < 0. 05).(2)The levels of TC,TG,HDL-C,LDL-C and blood viscosity in patients of the treatment group at 1 month and 3 months after treatment were different from those of the control group( P< 0. 05). Meanwhile,the levels of TC,TG,HDL-C,LDL-C and blood viscosity in patients of the treatment group at the 14th day after treament were significant different from those of 3 month after treatment(P < 0. 05).(3) The levels of TG,HDL-C,LDL-C and hematocrit in patients of the control group at 3 months after treatment were significantly different from those at pre-treatment(P < 0. 05). The CHOL and TG levels of the control group were different from those at pre-treatment at the 14th day after treatment( P < 0. 05).(4)There were significant differences between two groups at the 14th day,1 month and 3months after treatment in terms of therapy effect(Z= 5. 21,5. 54,3. 86;P = 0. 031,0. 024,0. 048). Conclusion The therapy of Danhong injection combined with Tongxinluo capsule can reduce the levels of Hcy,blood lipid,blood viscosity,and then improve the prognosis of patients with cerebral infarction.

Adolescent ; Adult ; Child ; Cord Blood Stem Cell Transplantation ; Female ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Leukemia, Myeloid, Accelerated Phase ; therapy ; Male ; Middle Aged ; Siblings ; Tissue Donors ; Transplantation, Homologous ; Young Adult

Objective To observe osteocyte survival and osteogenesis after nonvascularized free bone graft transplantation for canine mandible mass defect restoration. Methods An experimental canine premolar was extracted. 1 month later, the length of 3.0 cm edentulous mandible was cut off, as the same length as that nonvascularized and soft-free tissue complete ilium block was cut off and fixed into mandible defect in 40, 120 min. The survival osteocyte and osteogenesis of the nonvascularized graft were detected 4 and 8 weeks after transplantation. Results The continuity of canine mandible segmental defect of 3.0 cm length was repaired by free nonvascularized free bone graft, live osteocytes and osteogenesis were observed in non-vascularized free bone graft at off-body 40 min group in 4-8 weeks. But the nonvascularized free bone graft off-body 120 min was a dead bone, no survival osteocytes were observed, some osteoclasts were seen in the bone graft. Conclusion The length of 3.0 cm canine mandible defect can be restored by non-vascularized free bone graft; the osteocyte survival and osteogenesis are related to their off-body time before they are fixed into recipient.

Objective To study the value of echoeardiography for diagnosis of juxtaposition of atrial appendage(JAA) and to discuss its features. Methods Eehocardiographic characteristics of JAA in nine cases were compared with results of cardiac catheterization and operation. The diagnostic features of echocardiography were summarized. Results Seven cases had juxtaposition of left atrial appendage and two had juxtaposition of right atrial appendage. The nine cases were all associated with severe congenital heart disease and the most frequent malformations observed with JAA were double outlet right ventricle, transposition of great artery, single ventricle and so on. Direct visualization of the JAA in the parasternal short-axis view at the base of the heart and visualization of an unusual transverse orientation of the atrial septum were the most features of JAA. Echocardiographie characteristics of JAA cases were correspondent to the results of cardiac catheterization and operation. Conclusions There is high accuracy by echocardiography to diagnosis JAA. JAA should be alerted in severe congenital heart disease.