Objective: To explore the persistent viral response rate (SVR) in patients with refractory chronic hepatitis C after interferon (IFN) (peginterferon 360 μg qw) and ribavirin (PR) therapy failure. The SVR of patients with refractory chronic hepatitis C was improved by PR combined with direct antiviral agents (DAA) and proper extension of the course of therapy was applied. Methods: Seventeen cases of refractory chronic hepatitis C after IFN(peginterferon 360 μg qw) and ribavirin therapy failure were given PR combined with DAA treatment. The side effects were observed and corresponding adjustments were made on drug dosage, and SVR was recorded. Results: The 17 cases completed the whole course of treatment with PR combined with DAA for 24 weeks. All the 17 patients obtained rapid viralogical response (RVR) and SVR. After treatment, the SVR rate was 100% in patients including those with virologic relapse, retreated or previously non-responsive patients with refractory chronic hepatitis C. The adverse reaction of PR combined with DAA 24 weeks was generally mild. Conclusions The use of PR combined with DAA re-treatment in patients with refractory chronic hepatitis C can achieve SVR and shorten the treatment time. PR combined with DAA re-therapy is one of effective treatments to improve the rate of sustained viral response in patients with refractory chronic hepatitis C.

Objective To synthesize 18F-AlF-1,4,7-triazacyclononane-l,4,7-triacetic acid (NOTA)-c (CGRRAGGSC),which could specifically bind to the α chain of interleukin (IL)-11 receptor (IL-11 R),and evaluate its targeting potential to IL-11 R-positive tumors.Methods Polypeptide c (CGRRAGGSC) was first coupled with NOTA and then labeled with 18F by AlF labeling method.The radiochemical purity and radiochemical yield of 18F-AlF-NOTA-c(CGRRAGGSC) were analyzed by high performance liquid chromatography,and the stability in vitro was evaluated.The tracer biodistribution in tumor-bearing mice (cell line SKOV3) was evaluated by the dynamic imaging with microPET 30 min,1 h,2 h after injection of 18F-AlF-NOTA-c (CGRRAGGSC).The tracer kinetics was performed in normal mice.Pharmacokinetics parameters were calculated using DAS2.0 software.Results The radiochemical purity of 18F-AlF-NOTA-c(CGRRAGGSC) was higher than 95％ and the radiochemical yield was (30.0±7.4)％.It could be stably maintained in phosphatebuffered solution and plasma for at least 2 h.MicroPET imaging showed that 18F-AlF-NOTA-c(CGRRAGGSC)had a good affinity to SKOV3 tumor.The tumor/muscle ratios at 30 min,1 h,2 h after the injection of 18F-AlF-NOTA-c(CGRRAGGSC) were 6.26±2.98,7.19±3.63 and 9.05±4.30,respectively.The tracer was cleared rapidly in blood and mainly excreted by the liver and kidneys.The T1/2α and T1/2β were (0.38±0.14) h and (2.64±0.28) h,respectively.Conclusions 18F-AlF-NOTA-c(CGRRAGGSC) is easy to be synthesized and has a good affinity to IL-11R-positive tumors.It will be a potential IL-11R-targeting imaging agent.

Using Eu3+as a tracer,a sandwich?type assay was established. HE4 in serum specimens from 225 patients were detected by TRFIA. Serum levels of HE4 in pelvic tumors were quantitatively analyzed. From receiver operating characteristic (ROC) curves,the reference values was calculated for endometrial cancer,cervical cancer and ovarian cancer,respectively. Results The working range of serum HE4 for TRFIA was 10~10000 pmol/L with a sensitivity of 7.5 pmol/L. The method offered less interaction with CA125 and CA199,and also provided a better correlation with ECLA,while the CV of intra?assay was below 10%. HE4 levels were significantly higher in endometrial cancer,cervical cancer and ovarian cancer groups than in healthy volunteer group,while did not differ significantly between uterine fibroid group and healthy women group. As aging,the risk for developing pelvic tumors increased. The area of ROC for malignant tumors was all above 0.5 and the accurate interpretation of HE4 was 60 pmol/L. Conclusion A stable,precise HE4 TRFIA is well established,which is helpful in diagnosis of gynecologic cancers.

The J-curve phenomenon in the antihypertensive treatment of cardiovascular disease has had more theoretical and experimental evidence and has been recognized by most researchers.However,there are a few related studies and reports about whether antihypertensive treatment has the J-curve phenomenon in ischemic stroke.It has not yet reached a consensus.This article reviews this phenomenon and expecting it to contribute to the blood pressure mangement of ischemic stroke.

Lysophosphatidic acid (LPA) is a newly discovered multi-function "phospholipid messenger" which is primarily from platelet activation,and is involved in a variety of biological effects,and closely correlated with carcinoma growth,invasion and metastasis.LPA plays an important role in carcinoma development.There is a certain degree of clinical significance of LPA in some carcinoma diagnosis and prognosis.

Objective To study the clinical type and features of cerebral watershed infarction (CWI)in eldedy patients and its relationship with plasma lysophosphatidic acid(LPA).Method Analyzed the clinical data of 106 cases of CWI patients(CWI group)confirmed by cranial MRI,and compared plasma LPA levels in patients with different types of CWI,non-CWI patients(non-CWI group,36 cases)and healthy controls(control group,32 cases).Results In CWI group,anterior-cortex type 22 cases,LPA(4.93±0.72)μmol/L,posterior-cortex type 17 cases,LPA(4.75±0.81)μmoi/L,subcortical type 47 cases,LPA (5.46±1.03)μmol/L,mixed type 20 cages,LPA(6.02±1.12)μmol/L.In non-CWIgroup,LPA(5.37±1.24)μmol/L.In control group,LPA(2.92 ±0.36)μmol/L.The levels of LPA significandy increased in various types of CWI(P<0.05 or<0.01).of which mixed type and subcortical type were the highest,and the level of LPA in mixed type WaS higher than that in anterior-cortex type and posterior-cortex type(P<0.05).The level of LPA in non-CWI group was higher than that in control group,but there wss no significant difference compared with various types of CWI.Conclusions Subcortical type is the primal type in elderly CWI patients,the main cause of which is the atherosclerotic plaque formation and lumen stenosis.Platelet activation and its microemboli play an important role in the pathophysiology.LPA levels are significantly higher in various types of CWI,of which mixed type is the highest.LPA can be used as an important molecular marker to guide the sub-type treatment of CWI in elderly patients.

Objective To investigate the protective effect and its mechanism of prescription Zu Zhong 1 Hao (a traditional Chinese medical prescription, including Astragalus membranaceus, Atractylodes macrocephala, Arisaema cure Bile, Rhizoma pinelliae, the seed of Prunus persiea , Angelica sinensis , Ligusticum Chuanxiong, Paeonia lactiflora , and Pueraria ,etc) pretreatment on focal cerebral ischemia-reperfusion in rats. Methods Sixty SD rats were randomly divided into sham-operation, ischemia-reperfusion, flunarizine and prescription Zu Zhong 1 Hao low-, medium-and high-dose groups (n=10 in each group). A rat model of focal cerebral ischemia-reperfusion was induced by suture method (ischemia for 3 hours followed by reperfusion for 24 hours). Nitric oxide (NO) was measured by the nitrate reductase method; superoxide dismutase (SOD) activity was assessed by the xanthine oxidase method; maiondialde-hyde (MDA) was determined by the thiobarbiturie acid method; and tumor necrosis factor-a(TNF-α) was detected by the enzyme-linked immunosorbent assay (ELISA) method. Results Prescription Zu Zhong 1 Hao significantly improved neurological deficits in focal cerebral ischemia-reperfusion in rats, reduced the content of NO and MDA in brain tissue, increased SOD activity, and down-regulated the expression of TNF-α. Among them, the role of the high-dose group was more significant (P<0. 01). There were also significant differences between the low-and medium-dose groups and the ischemia-reperfusion group (P<0. 05). Conclusions The pretreatment of prescription Zu Zhong 1 Hao has the protective effect on focal cerebral ischemia-reperfusion injury, and its mechanism may be associated with the decreased content of NO and MDA in brain tissue, increased SOD activity, and down-regulated TNF-α expression.

Objective To observe the effects of different antithrombotic interventions on the changes of plasma lysophosphatidic acid (LPA) level in patients with nonvalvular atrial fibrillation (NVAF) and to provide the basis for clinical antithrombotic therapy. Methods A total of 235 patients with NVAF who did not receive antithrombotic therapy diagnosed by clinical and auxiliary examinations were randomly allocated to receive aspirin (100 mg/d) plus dipyridamole (100 mg/d) (n =76), aspirin (100 mg/d) plus fixed-dose warfarin (1.25 mg/d) (n =79), and dose-adjusted warfarin (international normalized ratio (INR) range of 1.5 to 2. 1) (n =80). They gore redivided into <60, 60-75, and ≥76 year-old groups according to their age. The plasma LPA levels were measured and compared before treatment and 2 and 6 weeks after treatment. Results 1he plasma LPA levels were decreased more significantly in the aspirin plus fixed-dose group than those in the aspirin plus dipyridamole and dose-adjusted warfarin groups (all P < 0.01). Two and 6 weeks after treatment with aspirin plus dipyridamole in the < 60 year-old group, the plasma LPA levels were significantly lower than those before treatment (all P<0. 01). Two and6 weeks after treatment with aspirin plus fixed-dose warfarin in the < 60 year-old group, the plasma LPA levels were significantly lower than those before treatment (all P <0. 01). Two and 6 weeks after treatment with aspirin plus fixed-dose warfarin in the 60-75 year-old group, the plasma LPA levels were significantly lover than those before treatment (all P <0.01). Two and 6 weeks after the treatment with dose-adjusted warfarin (INR 1.5-2. 1) in patients in each age group, the plasma LPA levels were significantly lower than those before treatment. Conclusions 1he different antithromhotic therapeutic modalities have different effects on platelet activation in patients with NVAF in different age groups. The patients in the < 60 year-old group can receive aspirin plus dipyridamole, the patients in the < 75 year-old group can receive aspirin plus fix-dose warfarin, and the patients > 75 year-old, dose-adjusted warfarin (INR 1. 5-2. 1) should he recommend.

Objective To investigate the changes of plasma lysephosphatidic acid (LPA) or acidic phospholipids (AP) levels in patients with nonvalvular atrial fibrillation(NVAF) or NVAF associated with silent brain infarction (SBI) and to provide biochemistry evidence to antithrombotic therapy. Methods Plasma LPA/AP levels was examined in blood freshly sampled in 235 cases of NVAF who were not receiving any antithrombotic therapy, 116 cases SBI who were not with NVAF and 120 cases healthy volunteers as control enrolled in the LPA and stroke prevention study. Plasma LPA was assayed by measuring its inorganic phosphorus after separation by chromatograph. Meanwhile, the platelet activation in NVAF or (and) SBI were observed. Results SBI was found in 31.5% of the participants with NVAF, and in 37.6% of the elderly NVAF subjects (age60 years old). LPA/AP levels were significantly increased in NVAF with SBI group((3.78±0.61) μmol/L) compared with controls ((2.66±0.49) μmol/L, 95% CI 3.47-4.21,P = 0.000), NVAF without SBI group ((3.29±0.57) μmol/L, 95 % CI 3.01-3.76, P = 0.008), SBI without NVAF group((3.17±0.54) μmol/L, P=0.004). The platelet activation was significantly higherin NVAF with SBI group, the odds ratio (95% CI) was 21.39(10.17 to 45.02),than those in NVAF without SBI group (P<0.01). Conclusion The plasma LPA/AP levels were significantly elevated in NVAF or NVAF with SBI, NVAF contributes to the risk of SBI. Platelet activation may play an important role in the pathogenesis of thromboembolism in NVAF and the measurement of LPA reflects activation of platelets in vivo and may be a useful marker for the diagnosis of thrombosis or prothrombotic states.Consideration of the role of antiplatelet therapy should be given when choosing antithrombotic therapy to NVAF-associated ischemic stroke.

To improve the teaching quality of advanced students on minimally invasive surgery is important for the generalization of new techniques on this subject.The teaching plan should be made according to the academic level of these students.Both theory learning and clinical practice should be emphasized.Multimedia tools should be adopted and English teaching should not be neglected.All these means help to better the teaching quality of advanced students on minimally invasive surgery.