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1.
《药学学报(英文版)》2020,10(7):1294-1308
A great challenge in multi-targeting drug discovery is to identify drug-like lead compounds with therapeutic advantages over single target inhibitors and drug combinations. Inspired by our previous efforts in designing antitumor evodiamine derivatives, herein selective histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) dual inhibitors were successfully identified, which showed potent in vitro and in vivo antitumor potency. Particularly, compound 30a was orally active and possessed excellent in vivo antitumor activity in the HCT116 xenograft model (TGI = 75.2%, 150 mg/kg, p.o.) without significant toxicity, which was more potent than HDAC inhibitor vorinostat, TOP inhibitor evodiamine and their combination. Taken together, this study highlights the therapeutic advantages of evodiamine-based HDAC1/TOP2 dual inhibitors and provides valuable leads for the development of novel multi-targeting antitumor agents.  相似文献   
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Purpose

To evaluate the feasibility of a same-day yttrium-90 (90Y) radioembolization protocol with resin microspheres (including pretreatment angiography, lung shunt fraction [LSF] determination, and radioembolization) for the treatment of hepatocellular carcinoma (HCC) and liver metastases.

Materials and Methods

All same-day radioembolization procedures performed over 1 y (February 2017 to January 2018) were included in this single-institutional retrospective analysis, in which 34 procedures were performed in 26 patients (median age, 63 y; 13 women), 19 with liver metastases and 7 with HCC. Yttrium-90 treatment activities were calculated by body surface area method. Tumor imaging response was assessed by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 for liver metastases and modified RECIST for HCC. Clinical side effects and adverse events were graded per Common Terminology Criteria for Adverse Events version 4.0.

Results

All planned cases were technically successful, and no cases were canceled for elevated LSF or vascular anatomic reasons. Pretreatment angiography modified the planned 90Y treatment activity in 1 case in which vascular anatomy required a lobar-dose split into 2 for segmental infusions. In 18% of cases, patients were briefly admitted after the procedure for observation or symptom management. Imaging evaluation of initial efficacy at 1 month demonstrated partial response in 25% and stable disease in 67% of patients with liver metastases and partial/complete response in 43% and stable disease in 14% of patients with HCC. Grade ≥ 3 adverse events occurred in 6% of cases, with no systemic therapy–limiting toxicities. The mean total procedure time was 4.2 hours.

Conclusions

A same-day 90Y radioembolization protocol with resin microspheres is feasible in select patients, which can expedite cancer therapy.  相似文献   
4.
This report describes a technique for measuring lung shunt fraction (LSF) twice in a single session during planning arteriography for radioembolization using low and standard dose technetium-99m macroaggregated albumin (99mTc-MAA). A patient with a 16.0 cm hepatocellular carcinoma and LSF of 70% was treated with lenvatinib for 4 weeks. Planning arteriography with administration of 0.5 millicuries of 99mTc-MAA was then performed. Arterial access was maintained while the LSF was calculated, which was persistently elevated at 54%. Embolization of arteriovenous shunts was performed during the same session and 5.0 millicuries of 99mTc-MAA were administered. The repeat LSF was 29%. Successful radioembolization was subsequently performed.  相似文献   
5.
目的 评价缺血修饰性白蛋白(ischemia modified albumin,IMA)对急性缺血性胸痛(ICP)的早期诊断价值。方法 时206例发病〈12h、表现为急性胸痛的患者立即行12导联心电图(ECG)检查,并抽血进行IMA、肌钙蛋白I(cTnI)、肌酸激酶同工酶MB(CK-MB)测定。将ECG、IMA、cTnI、CK-MB的结果单独或结合与最终诊断为非缺血性胸痛(NICP)及ICP的相互关系进行比较。结果 最后诊断为ICP98例,NICP108例,ICP发病〈3h和3-6h组IMA水平明显升高,与NICP组比较差异有统计学意义(P〈0.001);ICP发病〉6h组IMA水平与NICP组比较差异无统计学意义(P〉0.05)。IMA诊断发病〈3hICP的敏感性和阴性预测值(NPV)为89.1%和88.8%,明显高于ECG、cTnI和CK-MB,四者结合为97.6%和96.9%;IMA诊断发病3~6hICP的敏感性和NPV为71.7%和74.5%,也高于ECG、cTnI、CK-MB,四者结合为95.5%和94.2%;但IMA对于发病〉6h的ICP则无诊断作用。结论 IMA是诊断ICP的早期敏感生化指标,对于发病〈6h(尤其是〈3h)的ICP诊断具有较高的敏感性和NPV,优于ECG、CK-MB、cTnI;将IMA与其他指标结合,可进一步提高对ICP的诊断价值。  相似文献   
6.
BACKGROUND: In patients with chronic kidney disease (CKD), although strong associations have been observed between malnutrition and atherosclerosis, the relationship between serum albumin concentration and angiographic changes of coronary artery disease (CAD) remains poorly explored. The goal of the present study was, in patients with CKD, to clarify the relationship between the angiographic severity of CAD and serum albumin concentration reflecting either inflammation or nutrition or both. METHODS: In this study, 100 end-stage renal disease (ESRD) patients were enrolled, who commenced long-term dialysis therapy at our hospital and underwent coronary angiography within 3 months of the first haemodialysis (HD) session. Mean age was 63+/-11 years, 20% of the subjects were female and 62% had diabetes. Severity of CAD was evaluated in terms of (i) number of vessels exhibiting CAD (>or=75% stenosis) and (ii) Gensini score (GS). Clinical characteristics and laboratory findings were recorded at initiation of long-term HD therapy. We then evaluated a possible association with the presence and degree of CAD. RESULTS: Sixty-four patients exhibited signs of CAD. Forty-one among them (64%) had multivessel disease. On univariate logistic regression analysis, age, diabetes and hypoalbuminaemia were significantly associated with multivessel CAD. Univariate linear regression analysis demonstrated a positive correlation of age and diabetes with GS, and an inverse correlation of BMI and serum albumin level with GS. Stepwise regression analysis showed age and serum albumin level to be independently associated with multivessel CAD and GS. The ROC curves demonstrated best cut-off levels of age and albumin for predicting multivessel CAD to be 70 years and 3.15 g/dl, respectively. CONCLUSION: Hypoalbuminaemia at the initiation of dialysis is an important predictor of advanced CAD, particularly in male and in diabetic patients. It may reflect mainly a state of inflammation. However, malnutrition as a confounding factor cannot be entirely excluded.  相似文献   
7.
对血清蛋白白球比值参考范围的修改及其临床应用   总被引:1,自引:0,他引:1  
目的探讨血清蛋白白球比值(A/G)的参考范围和A/G在计算过程中产生的误差对临床应用的影响。方法①选取健康查体人员统计其A/G参考范围;②从理论上分析A/G计算误差的存在。结果①以统计结果的2s置信区间作为A/G的参考范围是1.1~2.2;②A/G计算值的误差会远大于相应总蛋白和白蛋白的测定误差。结论A/G较合适的参考范围为1.1~2.2,并且在临床应用中仍可根据实际情况降低其范围的下限。  相似文献   
8.
BACKGROUND: Microalbuminuria and macroalbuminuria constitute risk factors for ESRD and death in non-transplanted populations. Whether microalbuminuria (especially in non-proteinuric patients) and macroalbuminuria constitute risk factors for graft loss and death is presently unknown in renal transplantation. METHODS: We retrospectively assessed the association between urinary albumin excretion (UAE) and ESRD and death in renal transplantation. RESULTS: UAE was measured in 616 (397 proteinuric; 219 non-proteinuric patients) renal transplant recipients. They were grafted for 62 months (range: 6-192). During the 40 months (3.7-99) thereafter, 31 patients underwent dialysis and 32 died. Microalbuminuria (vs. normoalbuminuria) and macroalbuminuria (vs. microalbuminuria) were powerful risk factors for graft loss [OR: 14.25 (2.88-52.3) and 16.41 (7.46-36.0), respectively, both p < 0.0001], even after adjustments on renal function and diabetes. Among the 219 non-proteinuric patients, microalbuminuria (vs. normoalbuminuria) was a significant risk factor for graft loss [OR: 23.09 (1.93-276.4), p = 0.0132]. Both microalbuminuria (vs. normoalbuminuria) [OR: 5.55 (2.43-12.66), p < 0.0001] and macroalbuminuria (vs. microalbuminuria) [OR: 4.12 (1.65-10.29), p = 0.0024] were predictive of death. CONCLUSIONS: Microalbuminuria and macroalbuminuria are powerful independent predictors of ESRD and death. Microalbuminuria is a risk factor for graft loss even in non-proteinuric patients. UAE provides additional information on renal and patient prognosis as compared to proteinuria and renal function.  相似文献   
9.
BACKGROUND: Chronic kidney disease patients who are resistant to erythropoietin (EPO) treatment may suffer from malnutrition and/or inflammation. METHODS: In a cross-sectional study of haemodialysis patients, we investigated the relationship between the natural logarithm of the weekly EPO dose normalized for post-dialysis body weight and outcome measures of nutrition and/or inflammation [BMI, albumin and C reactive protein (CRP)] by means of multiple linear regression analysis. On the basis of the decile distribution of weekly EPO doses, we also evaluated four groups of patients: untreated, hyper-responders, normo-responders and hypo-responders. RESULTS: Six hundred and seventy-seven adult haemodialysis patients were recruited from five Italian centres. BMI and albumin were lower in the hypo-responders than in the other groups (21.3+/-3.8 vs 24.4+/-4.7 kg/m(2), P<0.001; and 3.8+/-0.6 vs 4.1+/-0.4 g/dl, P<0.001), whereas the median CRP level was higher (1.9 vs 0.8 mg/dl, P = 0.004). The median weekly EPO dose ranged from 30 IU/kg/week in the hyper-responsive group to 263 IU/kg/week in the hypo-responsive group. Transferrin saturation linearly decreased from the hyper- to hypo-responsive group (37+/-15 to 25+/-10%, P = 0.003), without any differences in transferrin levels. Ferritin levels were lower in the hypo-responsive than in the other patients (median 318 vs 445 ng/ml, P = 0.01). At multiple linear regression analysis, haemoglobin, BMI, albumin, CRP and serum iron levels were independently associated with the natural logarithm of the weekly EPO dose (R(2) = 0.22). CONCLUSIONS: Our findings support a clear association between EPO responsiveness and nutritional and inflammation variables in haemodialysis patients; iron deficiency is still a major cause of hypo-responsiveness.  相似文献   
10.
目的:重症脑出血微创术后气管切开病人痰培养病原菌分布与耐药情况分析,其院内感染发生的原因、探讨防治对策。方法:应用痰培养检出的病原菌及耐药性分析。结果:重症脑出血微创术后气管切开病人下呼吸道感染41例,其中G-杆菌26例占63.4%,G 球菌15例占36.6%,其中金葡菌11例,药敏仍以敏感菌株为主,但耐药菌株有增多趋势。结论:重症脑出血微创术后气管切开病人下呼吸道感染以G-杆菌为主,G 球菌以金葡菌为主,仍以敏感菌珠为主,耐药有增多趋势。万古霉素对G 球菌,氨曲南对G-杆菌敏感性较敏感,故在培养结果未出来之前经验用药是非常重要的。  相似文献   
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