Endocarditis ; Heart Valve Prosthesis ; Humans ; Pichia

Objective To explore the clinical features, diagnosis and interventional management of acute deep venous thrombosis of lower extremity (LEDVT)combined with type Ⅱ heparin-induced thrombocytopenia (HITⅡ) and to improve the knowledge of this disease. Methods A retrospective review and analysis of the clinical data of the patients with acute LEDVT combined with HIT Ⅱ enrolled from January 2010 to June 2014. All of them underwent anticoagulation with low molecular weight heparin (LMWH) and the comprehensive interventional therapy at the beginning of treatment.When HIT Ⅱ was
identified, all forms of heparin and LMWH were avoided . Alternative anticoagulation was commenced with argatrobam. Adjustments in interventional therapy were taken while the short-term low-dose glucocorticoid treatment were used.The clinical manifestations, changes of PLT, 4Ts score (Warkentin 4T scoring system, 4Ts) , HIT antibody assay (ELISA) and response to therapy of the patients were analyzed and the treatment effect was observed . The efficacy of interventional therapy was evaluated according to the improvement clinical symptoms and venography. Results The incidence of acute LEDVT combined with HIT Ⅱ was 1.9%(8/416). There were 4 males and 4 females with a median age of 24 years in this study. The median time between their initiation exposure to heparin and onset of thrombocytopenia was 5 days (range,3 to 8 days). The median platelet counts prior to HIT Ⅱ was 218 × 109/L( range,122 × 109/L to 254 × 109/L ). Platelet counts decreased to the lowest level range from 20 × 109/L to 51 × 109/L(median 32 × 109/L). After alternative anticoagulation, the interval period which PLT recovered to the basic level was range from 3 to 7 days (median 3.5 days) . According to the score of 4Ts , there were 2 cases score 6 and 6 cases score 8. HIT antibody assay (ELISA) was detected in 6 patients which the results were positive. During heparin anticoagulation treatment, the LEDVT condition of all patients continued to deteriorate. Vein thrombosis extended in 7 patients. Among them, 5 patients occurred new thrombosis in the inferior vena cava and(or) at the vessel of catheter insertion. Another 2 patients complicated with pulmonary embolism. After underwent anticoagulation with argatrobam , with the increased of PLT the treatment efficacy of thrombolysis therapy was ameliorated. At the endpoint of interventional therapy, the curative effect evaluation was excellent in 3 cases, good in 3 cases and medium in 2 cases respectively. All patients were followed up for 12 to 20 months (median 15.5 months) with no evidence of recurrence .Conclusions The study showed that acute LEDVT combined with HITⅡdisplayed the following features:(1)an absolute drop in platelet count below the normal range (PLT ≤100 × 109/L) or as a relative decrease of 30% to 50% from baseline counts. (2) refractory venous thrombosis,during the interventional treatment of acute LEDVT, platelets counts should be monitored regularly in patients who receiving heparin anticoagulation. For patients with strongly suspected HIT Ⅱ, withdrawal of all forms of heparin and early introduction of alternative anticoagulant therapy can improve the effect of interventional therapy.

Objective To discuss the clinical application of mechanical thrombectomy with AngioJet system for acute lower limb arterial ischemia (ALI).Methods A total of 12 ALI patients,who underwent percutaneous mechanical thrombectomy with AngioJet systemn during the period from January 2015 to November 2016,were enrolled in this study.The clinical data were retrospectively analyzed.The blood flow classification score after thrombolysis in myocardial infarction (TIMI) was used to evaluate the blood perfusion condition,and Cooley standard of efficacy score was used to assess the clinical curative effect.Results The technical success rate of mechanical thrombectomy with AngioJet system was 91.7％ (11/12).The average restored perfusion time was (1.5±0.6) hours.The clinical success rate and limb salvage rate were 83.3％ (10/ 12) and 91.7％ (11/12),respectively.The TIMI flow scores were improved from preoperative grade 0 (n=8) and Ⅰ (n=4) to postoperative grade 0 (n=1),Ⅰ (n=3) and Ⅱ (n=8).In 11 patients (91.7％) the symptoms of lower limb arterial ischemia were strikingly improved after mechanical thrombectomy.In one patient,the postoperative TIMI flow score remained 0 as preoperative state and the symptoms of lower limb arterial ischemia were not improved although catheter directed thrombolysis therapy was employed for 24 hours,and above-knee surgical amputation had to be carried out.Cooley efficacy score showed that complete cure was seen in 4 patients (33.3％),good response in 6 patients (50.0％),general improvement in one patient (8.3％) and pool response in one patient (8.3％).No severe bleeding complications occurred.Conclusion Percutaneous mechanical thrombectomy with AngioJet can rapidly recover the blood perfusion in patients with ALI,thus,further deterioration of the disease can be prevented and the limb salvage rate can be improved.Therefore,this technique has good clinical application value.

Objective:To explore the effects of genistein-3'-sodium sulfonate (GSS) on on motor function and brain autophagy levels in Parkinson disease (PD) model mice.Methods:Forty C57BL/6J mice were randomly divided into control group, model group, low-dose GSS group (0.15 mg/kg), medium-dose GSS group (0.50 mg/kg) and high-dose GSS group (1.50 mg/kg), with 8 mice in each group.Mice in the model group and the high, medium, and low-dose GSS groups were injected intraperitoneally with 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine to establish the PD mouse model, then mice in high, medium and low-close GSS group were intraperitoneally injected with corresponding doses of GSS (once a day for 21 days). The mice in model group were injected with equal volume 0.9% sodium chloride solution(once a day for 21 days), while the control group mice were fed normally.After 21 days, the motor and cognitive abilities of mice were evaluated by gait analysis, open field test, rotarod test, and modified Y maze test.Western blot was used to detect the expression levels of LC3-Ⅱ and Beclin-1 proteins in the cerebral cortex and striatum tissues of mice.SPSS 26.0 software was used for data analysis.One-way ANOVA was used for normal distribution data comparison among multiple groups, and LSD test was used for further pairwise comparisons, while Kruskal-Wails H test was used for non normal distribution data comparison. Results:(1) Gait analysis showed that there were statistically significant differences in the stride length of left forelimb, left hindlimb, right hindlimb( F=5.93, 6.21, 3.78, all P<0.01) and regularity index( H=14.409, P<0.01). The regularity index of the model group mice was lower than that of the control group ( P<0.05), and the regularity indexes of the low, medium, and high-dose GSS groups were all higher than that of the model group (all P<0.05). (2)In the open field test, there were statistically significant differences in the total distance and speed of movement among the 5 groups ( F=5.49, 5.49, both P<0.01). The total distance and speed of movement in the model group were both lower than those in the control group (both P<0.05). The total distance and speed of movement in the medium-dose GSS group( (2 395.57±319.35) cm, (7.98±1.06) cm/s) and high-dose GSS group ((2 386.51±396.00) cm, (7.95±1.32) cm/s) were higher than those of the model group ((1 863.31±278.96) cm, (6.21±0.93) cm/s) and the low-dose GSS group ((1 956.90±297.15) cm, (6.52±0.99) cm/s) (all P<0.05). (3) In the rotarod test and modified Y maze test, there were significant differences in latency to fall and residence time among the 5 groups ( F=58.41, 9.90, both P<0.01). The latency to fall and residence time of model group were lower than those of control group (both P<0.05), while those in the medium-dose and high-dose GSS groups were higher than those in the model group and low-dose GSS group (all P<0.05). (4) Western blot results showed that there were significant differences in the expression levels of LC3-Ⅱ/LC3-Ⅰ ratio ( F=8.17, 15.47, both P<0.01)and Beclin-1 protein( F=29.07, 20.54, both P<0.01) in cerebral cortex and striatum among the five groups.The LC3-Ⅱ/LC3-Ⅰ ratio and Beclin-1 protein levels in the cerebral cortex ((0.51±0.14), (0.46±0.06)) and striatum ((0.58±0.09), (0.55±0.10)) of the model group were lower than those in the control group (cerebral cortex: (1.00±0.10), (1.00±0.05), striatumm: (1.00±0.06), (1.00±0.25), all P<0.01). The LC3-Ⅱ/LC3-Ⅰratio and Beclin-1 protein in the medium-dose GSS group were higher than those in the model group, low-dose and high-dose GSS groups in both cerebral cortex and striatum (all P<0.05). The level of Beclin-1 of cerebral cortex in model group was lower than those in various doses of GSS group(all P<0.05). There were no statistically significant differences of Beclin-1 protein levels between the model group mice and various doses of GSS groups in striatum (all P>0.05). Conclusion:GSS can improve the motor and cognitive functions of PD model mice, and the mechanism may be related to the upregulation of autophagic activity in the cerebral cortex and striatum of mice.

Malignant bone tumors, one of the most common bone tumors includes osteosarcoma, Ewing's sarcoma, multiple myeloma, and metastatic bone tumors etc. These tumors are often accompanied by distant metastatic lesions at time of diagnosis, leading to low 5-year survival rates. At present, the use of biomarkers for early detection in order to facilitate early treatment are very limited. Therefore, most medical researchers are exploring the roles of exosomes in detecting malignant bone tumors. Exosomes are extracellular microvesicles secreted by different types of cells, which exist in a variety of body fluids. They are new intercellular information carriers that play important physiological roles. Current literature have reported that the RNA contained in exosomes (such as mRNA, miRNAs, lncRNAs and circRNAs) play important roles in the incidence as well as development of malignant bone tumors. However, the previous studies mostly focused on the roles of exosomal RNA in malignant bone tumor diseases, in tumor cell proliferation or apoptosis, transfers, evasion of immune surveillance and chemotherapy drug resistance etc. However, exosomal RNAs may function in the whole process of the disease progression via regulation networks. Our review of existing literature revealed that exosomal RNAs affacted the proliferation, metastasis, immune evasion and drug resistance of five common malignant bone tumors; Osteosarcoma, Ewing sarcoma, Chondrosarcoma, multiple myeloma, and metastatic bone tumors. Therefore, by elucidating on the mechanism of exosomal RNAs in the occurrence and development of malignant bone tumors, this study, could provide new ideas for early diagnosis, concomitant diagnosis, efficacy estimation (chemotherapy, radiotherapy and immunotherapy, etc.) as well as assessing the prognosis of malignant bone tumors.

Hereditary multiple exostoses (HME) are benign bone tumors characterized by autosomal dominant inheritance, which can cause skeletal malformation in adolescents, seriously affecting the body's aesthetic and motor functions. Currently, there are no guidelines for diagnosing and treating HME, and the main treatment is surgical treatment to remove the tumor and correct the deformity. However, osteochondroma is multiple and difficult to be completely resected. Therefore, more and more scholars are exploring the method of conservative treatment. However, the current understanding of the pathogenesis of HME is limited, and there are no safe and effective drugs in the clinic. Most hypotheses regarding the pathogenesis of HME are based on genetic mutations. Patients with HME may have EXT tumor suppressor gene mutations and function loss caused by secondary mutations such as loss of gene heterozygosity, which ultimately induce abnormal proliferation and differentiation of cartilage in growth plates. Abnormal EXT gene expression causes a decrease in the level of heparan sulphate (HS), leading to abnormalities in multiple molecular pathways that regulate the development and differentiation of growth plate chondrocytes, which together participate in the entire process of HME development and progression. This paper reviews the relevant studies on the pathogenesis of HME in recent years, in order to better understand the pathological process of HME, provide a theoretical basis for the diagnosis and treatment of HME, and also provide ideas for the development of drugs targeting HME.

Objective To evaluate the clinical value of percutaneous AngioJet thrombectomy for acute iliofemoral deep venous thrombosis.Methods 50 patients were divided into AngioJet thrombectomy group(25 cases) compared with bolus injection of urokinase through catheter in control group (25 cases).When the thrombosis was completely dissolved,the PTA and stents were implanted in those patients presenting May-Thurner syndrome in both groups.Inferior vena cava filter was retrieved from the patients and the thrombolytic therapy was discontinued.The patency rate of iliofemoral venous was assessed by CTA at 1 and 6 months after the procedure.Results The average dosage of urokinase in AngioJet patients was (880 000 ± 354 000) units.The mean duration time of catheter-directed thrombolysis was (42.2 ± 16.7) hours and the average hospitalization time is (3.8 ± 0.8) days.Grade Ⅲ thrombolysis was achieved in 18 limbs and grade Ⅱ lysis in 6 limbs,grade Ⅰ lysis in 1 limb.The mean duration time of catheter-directed thrombolysis was (129.6 ± 32.2) hours.The average dose of urokinase was (4 100 000 ± 1 060 000) units and the average hospitalization time was (7.9 ± 1.4) days in control group.Grade Ⅲ thrombolysis was achieved in 10 limbs,grade Ⅱ lysis in 9 limbs and grade Ⅰ lysis in 6 limbs.The dosage of urokinase,duration time of catheter-directed thrombolysis,time in hospital and clinical effects were statistically different between the two groups (all P ＜ 0.05).There were no recurrent thrombosis in all the patients after 6 months of treatment.Venous patency was maintained in all patients with implanted stent.Conclusions Percutaneous AngioJet thrombectomy with adjunctive thrombolytic therapy is an effective,safe treatment modality in patients with acute iliofemoral vein thrombosis.