Objective To establish a rat model of venous thrombosis in a plateau hypobaric hypoxic environment and to investigate the effect of this environment on venous thrombosis.Methods A total of 144 healthy male SD rats were assigned randomly to four groups(n=36 rats per group):a plains sham operation(A)group,plains operation(B)group,plateau altitude 6000 m+sham operation(C)group,and plateau altitude 6000 m+surgery(D)group.Rats in A and B groups were maintained in a plains normoxic environment,while rats in C and D groups C and D were subjected to a plateau environment.Rats in the surgical groups underwent quantitative constriction to incompletely obstruct the inferior vena cava blood flow.Each group was further divided into subgroups based on time:1,3,5,7,14,and 21 d(n=6 rats per group).Regular vascular ultrasound monitoring was conducted,and blood samples were taken for whole blood viscosity testing and the assessment of inflammatory indicators,including endothelin-1(ET-1),interleukin-6(IL-6)and tissue factor(TF).Coagulation function was evaluated through the activated partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),fibrinogen(FIB)and D-dimer.After the observation period,the experimental animals were sacrificed and the limbs were removed.Thrombus samples were stained with hematoxylin/eosin(HE),and the thrombus wet mass was measured.Results The thrombosis incidence was significantly higher in the plateau D group than in B group,accompanied by a marked increase in blood viscosity and hematocrit(P＜0.01).Additionally,levels of ET-1,IL-6,and TF were significantly elevated(P＜0.05),indicating a coagulation disorder.Conclusions A plateau hypoxic environment model can be successfully simulated by quantitative coarctation of the inferior vena cava,combined with a specialized environmental chamber.The findings of this study suggest that a plateau hypoxic environment promotes venous thrombosis.

Objective To establish a rat model of venous thrombosis in a plateau hypobaric hypoxic environment and to investigate the effect of this environment on venous thrombosis.Methods A total of 144 healthy male SD rats were assigned randomly to four groups(n=36 rats per group):a plains sham operation(A)group,plains operation(B)group,plateau altitude 6000 m+sham operation(C)group,and plateau altitude 6000 m+surgery(D)group.Rats in A and B groups were maintained in a plains normoxic environment,while rats in C and D groups C and D were subjected to a plateau environment.Rats in the surgical groups underwent quantitative constriction to incompletely obstruct the inferior vena cava blood flow.Each group was further divided into subgroups based on time:1,3,5,7,14,and 21 d(n=6 rats per group).Regular vascular ultrasound monitoring was conducted,and blood samples were taken for whole blood viscosity testing and the assessment of inflammatory indicators,including endothelin-1(ET-1),interleukin-6(IL-6)and tissue factor(TF).Coagulation function was evaluated through the activated partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),fibrinogen(FIB)and D-dimer.After the observation period,the experimental animals were sacrificed and the limbs were removed.Thrombus samples were stained with hematoxylin/eosin(HE),and the thrombus wet mass was measured.Results The thrombosis incidence was significantly higher in the plateau D group than in B group,accompanied by a marked increase in blood viscosity and hematocrit(P＜0.01).Additionally,levels of ET-1,IL-6,and TF were significantly elevated(P＜0.05),indicating a coagulation disorder.Conclusions A plateau hypoxic environment model can be successfully simulated by quantitative coarctation of the inferior vena cava,combined with a specialized environmental chamber.The findings of this study suggest that a plateau hypoxic environment promotes venous thrombosis.

Objective To develop an effective method for delivering VEGF and CD47 double-modified exosomes to treat renal damage induced by heat stroke so as to reduce and repair renal damage.Methods A plasmid fusion-expressing VEGF and CD47 targeting renal injury was constructed,transfected into rat bone marrow derived mesenchymal stem cells (BMMSCs),and then fusion-exosomes were isolated and extracted.Transmission electron microscopy,nanoparticle tracking analysis,and Western blotting were used to identify the obtained exosomes.Rats were intravenously injected with 200 μg of DiD-labeled unmodified exosomes,VEGF-modified exosomes and VEGF-CD47 double-modified exosomes,respectively,through the tail vein,and the effects of exosomes on the kidneys were detected and analyzed using a small animal in vivo imaging instrument.A total of 60 SD rats were randomly divided into 6 groups,with 10 rats in each group,that is,blank control group (group A),heat stroke-induced renal injury model receiving PBS in 12,24 and 36 h after modelling (group B),empty plasmid group (group C),Exos group (group D),ExosVEGF group (group E) and ExosVEGF-CD47.Kidney tissue and blood samples were collected in 72 h after 3 times of treatment.Pathological changes in kidney tissue were observed at the tissue level and the damage were scored.Changes in serum blood urea nitrogen (BUN)and serum creatinine (Scr)levels were detected to evaluate the therapeutic effect.Western blotting and qRT-PCR were used to analyze the expression of the pro-inflammatory factors TNF-α and NF-κB,the proliferation regulatory signaling molecules Ki67,FGF2,pAMPK and pERK,and the fibrosis regulatory molecule FGF23,in order to comprehensively analyze the effects on proliferation and inhibition of fibrosis.Results BMMSCs and ExosVEGF-CD47 were successfully isolated and characterized,and a rat model of acute kidney injury was effectively constructed.Higher fluorescence intensity was found in the kidney tissue of the Exos VEGF-CD47group than the Exos-Ctrl group and Exos VEGF group (P<0.05).In 72 h after treatment,the ExosVEGF-CD47 group had significantly lower serum BUN and Scr levels (P<0.0001),and notably lower Tubular casts score (P<0.0001),decreased levels of pro-inflammatory factors TNF-α and NF-κB (P<0.0001),up-regulated Ki67 and FGF2 expression (P<0.05),and down-regulated FGF23 expression (P<0.0001)when compared with the AKI+Exos group and AKI+ExosVEGF group.Conclusion VEGF and CD47 show promise in targeting acute kidney injury induced by heat stroke,effectively mitigate damage and facilitate repair,which may be due to exosome-mediated inhibition of renal tissue inflammation,promotion of proliferation,and inhibition of fibrosis.

Objective:To reveal effect of celastrol(Cel)on apoptosis of liver and kidney cells in preeclampsia(PE)rats and its protective effect.Methods:Fifty pregnant SD rats were randomly divided into 5 groups(n=10):Control group,PE group,PE+low-dose Cel group(PE+L-Cel),PE+medium-dose Cel group(PE+M-Cel),PE+high-dose Cel group(PE+H-Cel),PE rat model was induced by injection of lipopolysaccharide through tail vein.Rats in PE+L-Cel group,PE+M-Cel group and PE+H-Cel group were intraperitoneally injected with 5,10 and 20 mg/(kg·d)Cel daily from 14～20 day of pregnancy.Control group and PE group were in-jected with equal volume of normal saline.Systolic blood pressure(SBP)and urine albumin of rats in each group were measured after treatment.Cell apoptosis of liver and kidney tissues were detected by TUNEL staining.Bcl-2 and Caspase-9 expressions in liver and kidney tissues were detected by immunohistochemical staining.ELISA was used to detect serum IFN-γ,IL-4,IL-17 and IL-10 levels.Results:Compared with PE group,SBP and urine albumin levels of PE+L-Cel group,PE+M-Cel group and PE+H-Cel group were decreased(P<0.05),cells apoptosis rates of liver and kidney tissues were decreased(P<0.05),positive expression of Caspase-9 was significantly reduced,Bcl-2 level was significantly increased,serum IFN-γ and IL-17 levels were reduced(P<0.05),while IL-4 and IL-10 levels were increased(P<0.05).Conclusion:Cel can reduce symptoms of PE rats and inhibit liver and kidney cell apoptosis,which may play a therapeutic effect by correcting imbalance of Th1/Th2 and Th17/Treg cells in PE rats.

Humans ; Cardiovascular Diseases/chemically induced* ; East Asian People ; Risk Factors ; Heart Disease Risk Factors ; Lipids ; Anticholesteremic Agents/adverse effects* ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Treatment Outcome

In China， the incidence of ischemic heart disease （IHD） is increasing year by year， which brings enormous burden to families and society. It is urgent to find preferable treatment methods and medical therapies. The Chinese ethnic minority medicine has gradually developed unique theoretical systems and therapeutic characteristics on the basis of clinical experience and thinking modes including image-number thinking and the holistic perspective. Consequently， it possesses huge application capacity and research value in prevention and treatment of IHD. Belonging to the medical system based on the view of nature and life， the Tibetan medicine， Mongolian medicine， and Dai medicine have respectively formed theories like "three elements" "three life-sustaining energies" "four elements and five skandhas （aggregates）" ， have put forward unique understandings of IHD and have formed corresponding therapeutic principles and methods， generating plentiful classic prescriptions represented by Sanwei Tanxiang powder， Bawei Chenxiang powder， Roukou Wuwei pills and Yajiao Hadun powder. They also contain characteristic ethnic medicine resources such as Choerospondiatis Fructus， Rhodiola Rosea and Draconis Sanguis. Aiming to provide enlightenment and reference for the clinical application and development of the Chinese ethnic minority medicine for the prevention and treatment of IHD， the authors try to summarize the related researches represented by Tibetan and Mongolian medicines， and then discuss the opportunities and challenges faced by such researches.

Objective To investigate the effect of Yangxue Rougan pills on a rat model of liver fibrosis induced by multiple factors and the mechanism of action of Yangxue Rougan pills in the treatment of liver fibrosis. Methods A total of 50 male rats were randomly divided into blank control group, multi-factor model group, Fuzheng Huayu capsule group, and high-, middle-, and low-dose Yangxue Rougan pill groups. The rats in the blank control group were given normal water and feed, and those in the other groups were given modified high-fat low-protein diet and 5% alcohol, as well as subcutaneous injection of olive oil solution containing 40% carbon tetrachloride and intraperitoneal injection of pig serum 0.5 mL per rat, twice a week for 12 consecutive weeks. Since week 7, the rats in the high-, middle-, and low-dose Yangxue Rougan pill groups were given Yangxue Rougan pills at a dose of 9.5, 4.75, and 2.38 g/kg, respectively, those in the Fuzheng Huayu capsule group were given Fuzheng Huayu capsules at a dose of 0.75 g/kg, and those in the blank control group and the multi-factor model group were given an equal volume of distilled water by gavage every day for 6 consecutive weeks. The rats were treated at week 12. HE staining and Masson staining were used to observe the degree of liver fibrosis in rats, and PCR and Western blot were used to measure the expression of TGF-β1, Smad3, and Smad7 in the liver. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the Dunnett's t -test was used for further comparison between two groups. Results Compared with the blank control group, the multi-factor model group had a severely damaged lobular structure and a significantly higher degree of liver fibrosis, with the formation of pseudolobules with different sizes; compared with the multi-factor model group, the Yangxue Rougan pill groups had a significant improvement in the degree of liver fibrosis, with the most significant therapeutic effect in the high- and middle-dose Yangxue Rougan pill groups. Compared with the blank control group, the multi-factor model group had significant increases in the expression of TGF-β1 and Smad3 and a significant reduction in the expression of Smad7 in liver tissue (all P < 0.05); compared with the multi-factor model group, the Yangxue Rougan pill groups had a significant reduction in the expression of TGF-β1 and a significant increase in the expression of Smad7 (all P < 0.05); compared with the multi-factor model group, the high- and middle-dose Yangxue Rougan pill groups had a significant reduction in the expression of Smad3 (both P < 0.05). Conclusion Yangxue Rougan pills can significantly inhibit liver fibrosis in rats by downregulating the expression of TGF-β1 and Smad3 and upregulating the expression of Smad7, and therefore, the TGF-β1/Smad signaling pathway is one of the mechanisms of action of Yangxue Rougan pills in improving liver fibrosis.

Objective:To explore the relationship between electrocardiogram QRS wave duration and pathological parameters of acute myocardial infarction and its prognosis.Methods:The patients with acute myocardial infarction treated in Hunan Brain Hospital from January 2018 to June 2019 were divided into normal group (≤110 ms, NG group) and extended group (>110 ms, EG group) according to the time limit of QRS wave group of electrocardiogram (ECG). The clinicopathological data of the two groups were collected, and the differences of relevant pathological parameters between the two groups were compared. The correlation between ECG QRS complex time limit and pathological parameters of acute myocardial infarction and the independent risk factors affecting the occurrence of malignant cardiovascular events after acute myocardial infarction were analyzed.Results:A total of 134 patients were enrolled, 73 in the EG group, and 61 in the NG group. The plasma levels of N-terminal pro-brain natriuretic peptide (N-proBNP) in EG group were significantly higher than those in NG group ( P<0.05), and left ventricular ejection fraction (LVEF) was significantly lower than that in NG group ( P<0.05). The time limit of QRS wave group in EG group was positively correlated with the plasma levels of N-proBNP ( r=0.981, P<0.001) and negatively correlated with LVEF ( r=-0.979, P<0.001). The ratio of Killip grade Ⅰ patients in EG group were lower than those in NG group ( P<0.05), while the ratio of grade Ⅱ and Ⅲ patients were significantly higher than those in NG group ( P<0.05), and there was no significant difference between the two groups in grade Ⅳ patients ( P>0.05). The incidence of malignant cardiovascular events (cardiogenic shock, malignant arrhythmia, acute pulmonary edema, cardiogenic death and re-infarction) in EG group was significantly higher than that in NG group ( P<0.05). Multivariate logistic regression analysis showed that elevated serum N-proBNP, decreased LVEF, prolonged QRS wave duration and high Killip cardiac function were independent risk factors for malignant cardiovascular events after acute myocardial infarction. Conclusions:After acute myocardial infarction, EG patients have worse cardiac function, higher incidence of malignant cardiovascular events and worse prognosis than NG patients.

Objective:To improve the awareness of neuroblastoma (NB) with cervical lymph node metastasis in children patients by summarizing the clinical features of such patients and analyzing their survival situation.Methods:The research analyzed the medical records of 225 patients with cervical lymph node metastasis of NB from April 1, 2007 to May 31, 2017 in Beijing Children′s Hospital, Capital Medical University.The treatment were divided into 2 phases according to treatment time (one from April 1, 2007 to December 31, 2011 and the other from January 1, 2012 to May 31, 2017). The survival situation and treatment effect in each phase were analyzed.The following up time ended at Jan 1, 2018.Results:(1)Clinical features: total 225 cases admitted in the research with about 37.3% of all the NB patients.One hundred girls(44.4%) and 125 boys(55.6%). The age from 2 months to 147 months, the me-dian age of patients was 37 months.The age under 18 months were 27 cases(12.1%). The majority primary site of tumor was located in retroperitoneal(174 cases, 77.3%) and mediastinum(48 cases, 21.3%). There were 33 cases which metastasic site confined to cervical lymph node(4N stage, 14.7%); 139 cases (62.1%) with bone marrow metastasis, 159 cases (71.0%) with bone metastasis.The number of patients in high-risk group was 208 cases(91.2%), while the low-risk and the medium-risk group was 17 cases(7.5%). (2)Treatment effect and survival analysis: a total of 200 cases received systemic treatment and followed-up in our hospital.The follow up time from 2 months to 123 months, the median follow up time was 23 months.The 3 year overall survival (OS) rate of all the patients was 56.4%, the 3 year event free survival (EFS) rate was 52.0%.While the 5-year OS was 46.5%, and the 5-year EFS was 39.7%.According to the first phase of treatment(April 1, 2007 to December 31, 2011), the 3-year EFS was 49.6%, and the 3-year OS was 54.4%, the 5-year EFS was 39.5%, and the 5-year OS was 44.7%.According to the second phase of treatment(January 1, 2012 to May 31, 2017), the 3-year EFS was 58.1%, and the 3-year OS was 57.3%.The 5-year EFS was 48.7%, and the 5-year OS was 46.8%.About the 4N patients, the 3-year EFS was 71.2%, and the 3-year OS was 82.2%.The 5-year EFS was 61.5%, and the 5-year OS was 76.7%.Conclusions:Cervical lymph node is one of the most common distant metastasis of NB.More than half of the patient with bone or bone marrow metastasis.The prognosis of patients′ metastatic disease limited to cervical lymph nodes(4N stage), but still worse than the foreigner haver reported.The probable reason is the proportion of high-risk patients in the center is higher than the foreign research.

Objective: To analyze and summarize the results of genomic DNA test findings of chemotherapeutic drugs commonly used in pediatric rhabdomyosarcoma (RMS) in children, and to analyze the relationship between adverse reactions to chemotherapy toxicity and genomic DNA polymorphisms, so as to provide evidence for guiding treatment. Methods: Retrospective analysis was conducted in RMS children admitted at Hematology Oncology Center, Beijing Children′s Hospital, Capital Medical University from January 2017 to June 2018.The criteria for enrollment were definite diagnosis of RMS, regular treatment and follow-up at Hematology Oncology Center, Beijing Children′s Hospital, Capital Medical University, and detection of peripheral blood DNA fluorescence hybridization sequence for several commonly chemotherapy drugs.The toxicity of chemotherapeutic drugs was detected based on the National Cancer Institute routine toxicity criteria (NCI-CTCAE version 4.0). Summary and analysis indicators included primary and metastatic site, size, international RMS clinical stage (TNM-UICC), Intergroup Rhabdomyosarcoma Study(IRS) Clinical Grouping Classification, risk grouping, pathological type, changes in major organ functions, as well as processes of surgery, chemotherapy and radiotherapy, and the association between toxicity and DNA polymorphism of drug genes was analyzed.SPSS 22.0 software was used for χ² test. Results: A total of 32 children were enrolled, and 20 cases were male and 12 cases were female, their median age was 50 months (15-120 months). The primary tumor of 9 cases were sited in the chest, abdomen and basin, 8 cases in the head and neck (non-meningeal), 7 cases in bladder prostate, 3 cases in limbs, 2 cases in the meningeal area, 1 case in urogenital tract (non-bladder prostate), 2 cases in other parts.Seventeen cases were embryonic type and 15 cases were alveolar type.Five cases were TNM-Ⅰ stage, 5 cases were TNM-Ⅱ stage, 10 cases TNM -Ⅲ stage, 12 cases were TNM-Ⅳ stage, 21 cases were IRS-Ⅲ, 11 cases were IRS-Ⅳ.Twenty-two cases were moderate-risk (MR), 10 cases were high-risk (HR). Twenty-two cases were detected UGT1A1*6 gene, 18 cases in GG type, 13 cases in GA type, and 1 case in AA type.ABCB1 gene monitoring was performed in 27 children, 14 cases of CT type and 13 cases of TT type; 29 cases were detected GSTP1 gene, 7 cases of GA type and 2 cases of GG type, 19 cases of AA type, 1 case of AG type; 30 cases were detected CYP3A5 gene, 2 cases of GA type, 13 cases of GG type, AG 15 cases.All patients were treated according to the BCH-RMS-2007 protocol using VAC (Vincristine, Doxorubicin, and Cyclophosphamide) as the basis for chemotherapy.From 2017, VAC and VI regimen (Vincristine, Irinotecan) were defined as the standard of backbone chemotherapeutic regimen for MR.Nine cases underwent surgery before chemotherapy and 10 cases had surgery after chemotherapy, among them, 5 cases underwent twice operation.Local radiotherapy was performed on the 12^th week of chemotherapy, and the central nervous system involvement cases started in the first week.Hematological toxicity was mainly caused by neutropenia, with 2 cases of grade 3 and 30 cases of grade 4.Liver function damage of grade 2 was 6 cases, grade 3 was 3 cases.Four patients with grade 1 diarrhea, 3 patients with grade 2, 5 patients with grade 3, 3 patients with grade 4.There was significant diffe-rence between the severity of diarrhea and UGT1A1*6 genotype polymorphism(P<0.05). Conclusions Chemothe-rapy for RMS patients is highly safety.If the genomic DNA test of chemotherapy drugs show a slow metabolism type, the dose of chemotherapy should be reduced, and the toxicity of chemotherapy drugs should be monitored dynamically.