透皮淋巴靶向长春新碱传递体

长春新碱(vincristine,VCR)临床主要用于治疗急性淋巴细胞白血病、何杰金及非何杰金淋巴瘤，疗效确切，但由于具有较大的神经系统毒性和局部刺激性，限制了其在临床上的应用。为增加VCR的淋巴靶向性，以增强疗效，降低其毒副作用，采用薄膜-超声分散法制备长春新碱传递体(VCR-T)，并考察其制剂学性质、药代动力学特征及靶向性。所制备的VCR-T平均粒径为63 nm，包封率为59%；改良Franz扩散池研究发现其体外透皮过程符合多项式方程，12 h累积透皮百分率为67.4%；HPLC法测定VCR在大鼠体内的药代动力学及组织分布，以VCR注射液为对照，VCR-T使VCR在血液中滞留时间延长了12倍，大鼠淋巴中靶向指数增加了2.75倍。传递体可良好地载带VCR透过皮肤进入体循环，具有较好的淋巴靶向性，可作为新型的淋巴靶向给药系统。     

尼莫地平对神经元退行性变模型小鼠脑组织中铁离子的影响研究

目的:探讨尼莫地平对神经元退行性变模型小鼠脑组织中铁离子的影响。方法:取小鼠随机分为假手术组(生理盐水)、模型组(生理盐水)和尼莫地平高、中、低(80、40、20mg.kg-1)剂量组,每组35只,后4组脑室内注射0.25氯化铝2μL,每天1次,连续5d,建立神经元退行性变小鼠模型,假手术组注射等体积人工脑脊液;5d后各组灌胃给予相应药物,每天2次,连续30d,末次灌胃24h后观察其脑组织的病理学变化,考察海马组织中丙二醛(MDA)、血红素加氧酶-1(HO-1)蛋白、铝离子和铁离子水平变化。结果:与模型组比较,尼莫地平高剂量组神经元损伤明显减轻,其中MDA、HO-1蛋白和铁离子水平明显降低(P<0.05);其余指标及尼莫地平中、低剂量组各项指标均无明显变化。结论:尼莫地平可能通过抑制HO-1蛋白表达维持铁离子代谢平衡,发挥缓解神经元退行性变的作用。     

脐血CD34+细胞向巨核系定向扩增的初步探讨

目的探讨不同细胞因子组合定向诱导CD34 细胞向巨核系分化的能力。方法利用免疫磁珠法(MACS)分离纯化脐血CD34 细胞,在无血清培养体系中以1×105/ml每孔接种,经不同细胞因子组合诱导培养。结果收集5份脐血标本,平均体积为95ml,CD34 细胞的比例为2.18%±0.89%,经过MACS分选后,CD34 细胞纯度平均可达81.55%。在细胞生长因子的刺激培养下,MK3组有核细胞数,CD34 细胞数,CD41a 细胞数在培养第16天分别达277.4倍、6.89倍、66.79倍,高于其它各组。结论脐血CD34 细胞体外在相关细胞生长因子的刺激下可向巨核细胞系定向分化。     

驻景丸加减方对形觉剥夺性近视小鼠视网膜自噬的影响

目的:探讨驻景丸加减方对形觉剥夺性近视小鼠视网膜自噬的影响。方法:C57BL/6小鼠30只随机分为阴性对照组、近视模型组以及中药干预组,每组10只。除了阴性对照组外,近视模型组、中药干预组小鼠均使用半透明EP管遮盖右眼制成形觉剥夺性近视(FDM)模型;中药干预组灌胃驻景丸加减方混悬液0.546g/(kg·d)(0.15mL/d),阴性对照组、近视模型组灌胃等量生理盐水(0.15mL/d),共4wk。分别于实验开始、实验结束,使用带状检影镜测量小鼠右眼屈光度,A超测量小鼠右眼眼轴长度。实验结束时,取所有小鼠右眼进行检测,免疫荧光法定位和检测视网膜小胶质细胞标志物(Iba1)活性与迁移;透射电镜观察视网膜色素上皮细胞中自噬小体形成情况;Western Blot、实时荧光定量PCR(q-PCR)检测视网膜组织自噬标志物LC3Ⅱ和p62蛋白定量及基因表达情况。结果:实验结束时小鼠右眼屈光度示,近视模型组、中药干预组形成相对近视,近视模型组、中药干预组较阴性对照组显著降低(均P<0.01)。实验结束时,近视模型组、中药干预组眼轴长度较阴性对照组眼轴长度显著增加(P<0.01)。免疫荧...     

瘫康Ⅱ号合剂的质量标准研究

目的:对瘫康Ⅱ号合剂的质量标准进行研究。方法:采用薄层色谱法对主药熟地黄、牡丹皮进行定性鉴别,并采用薄层色谱法对毒性药材附子进行限量检查。结果:主药薄层色谱定性鉴别特征性强,重现性好。限量检查方法简便易行。结论:瘫康Ⅱ号合剂质量标准稳定,操作方法简单,结果准确可靠,可作为该品种的内控标准。     

Numerical Simulation and Process Optimization on Hot Twist-Stretch Straightening of Ti-6Al-4V Alloy Profile

Ti-6Al-4V profiles prepared by hot extrusion are usually accompanied by bending and twisting. The hot twist-stretch straightening is an effective strategy such that the bending deflection and twisting angle can be simultaneously decreased by a single straightening process. In addition, utilizing stress relaxation effect, the residual stress and springback can be greatly reduced by holding the straightening temperature and strain constant for a period after twist-stretch straightening. In this study, the hot deformation behaviors of the Ti-6Al-4V profile were revealed by experiments. The tensile model was obtained by uniaxial tensile tests within ranges of temperatures (500–700 °C) and strain rates (5 × 10⁻⁵–1 × 10⁻³ s⁻¹). The creep constitutive model was acquired with stress relaxation experiments in ranges of temperatures (500–700 °C) and pre-strain of 1.5%. Then, the coupled thermo-mechanical model of hot twist-stretch straightening was established. Based on orthogonal experiment strategy, the effects of straightening temperature, stretch strain, and holding time on the bending deflection and torsion angle of profile were investigated systematically and the process was optimized. The straightening accuracy is significantly affected by straightening temperature and holding time. By using optimized process parameters in practical straightening experiments, the deflection/length and angle/length after straightening does not exceed 2‰ and 2.5‰°/mm, respectively, which is basically consistent with the numerical simulation result.     

Combination of C‐reactive protein,procalcitonin, IL‐6, IL‐8, and IL‐10 for early diagnosis of hyperinflammatory state and organ dysfunction in pediatric sepsis

BackgroundAlthough early diagnosis and management are critical for prognosis of pediatric sepsis, there are no specific diagnostic biomarkers for the hyperinflammatory state and organ dysfunction, important stages of sepsis.MethodsWe enrolled 129 children with infection into three groups: non‐sepsis infection (33), Sepsis 1.0 (hyperinflammatory state, 67), and Sepsis 3.0 (organ dysfunction, 29). Another 32 children with no infections were included as controls. Serum C‐reactive protein (CRP), procalcitonin (PCT), interleukin (IL)‐1β, IL‐2, IL‐4, IL‐5, IL‐6, IL‐8, IL‐10, IL‐12p70, IL‐17, tumor necrosis factor (TNF)‐α, interferon (IFN)‐α, and IFN‐γ were assessed to diagnose the two stages, and their diagnostic capacities were evaluated using receiver operating characteristic (ROC) curves. We also examined whether combining biomarkers improved diagnostic efficiency.ResultsSignificantly higher CRP, PCT, and IL‐6 levels were detected in the Sepsis 1.0 than the non‐sepsis infection group (p < 0.001). The areas under the curve (AUCs) for diagnosing Sepsis 1.0 were 0.974 (CRP), 0.913 (PCT) and 0.919 (IL‐6). A combination of any two biomarkers increased diagnostic sensitivity to ≥92.54% and specificity to 100.00%. Significantly higher PCT, IL‐8, and IL‐10 levels were found in the Sepsis 3.0 than the Sepsis 1.0 group (p ≤ 0.01), with AUCs for diagnosing Sepsis 3.0 0.807 (PCT), 0.711 (IL‐8), and 0.860 (IL‐10). Combining these three biomarkers increased diagnostic sensitivity to 96.55% and specificity to 94.03%.ConclusionIn pediatric sepsis, combining any two of CRP, PCT, and IL‐6 can accurately diagnose the hyperinflammatory state and increase diagnostic specificity. Early diagnosis of organ dysfunction requires a combination of PCT, IL‐8, and IL‐10.     

Efficacy and safety of transcatheter arterial chemoembolization-lenvatinib sequential therapy for patients with unresectable hepatocellular carcinoma: a single-arm clinical study

BackgroundRepeated transcatheter arterial chemoembolization (TACE) could cause ischemia of the tumor tissue and increases production of angiogenic factors in patients with hepatocellular carcinoma (HCC). Lenvatinib can inhibit the expression of angiogenic factors induced by ischemia after TACE and reduce angiogenesis and tumor recurrence. TACE-lenvatinib sequential therapy may improve clinical outcomes. There have been few investigations of TACE-lenvatinib sequential therapy for the treatment of unresectable HCC. We aimed to evaluate the efficacy and safety of TACE-lenvatinib sequential therapy for unresectable HCC.MethodsFrom May 2018 to May 2021, 53 consecutive patients who underwent TACE-lenvatinib sequential therapy were retrospectively reviewed. Of these, 30 patients who met the inclusion criteria were selected. Lenvatinib treatment started within 1 or 2 weeks after TACE at a dose of 8 or 12 mg once daily. Treatment response was assessed using dynamic magnetic resonance imaging (MRI) according to the modified response evaluation criteria in solid tumor (mRECIST). Blood tests were also performed at every response evaluation. Patients with complete response (CR) or partial response (PR) and stable disease (SD) received continuous lenvatinib therapy, and patients with progressive disease (PD) received repeated TACE. The progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were calculated. Statistical analysis was performed using the Kaplan-Meier method.ResultsThe median age was 58.5±9.1 years, and 16.7% (5/30) of patients were female. A total of 12 patients were categorized as Barcelona Clinic Liver Cancer (BCLC) Stage B and 18 were BCLC Stage C. The mean follow-up time was 15.7 months. The ORR was 76.7% (23/30), and the DCR was 96.7% (29/30). The median PFS was 6.1 months, and the median OS was 20.7 months. The most common lenvatinib-related AE was rash, and the most common TACE-related AE was elevated aspartate aminotransferase (AST). No treatment-related mortality was observed.ConclusionsFrom our findings, TACE-lenvatinib sequential therapy may prolong OS and PFS in patients with unresectable HCC, and the side effects are acceptable. The efficacy and safety of the sequential therapy should be confirmed in multiple center randomized controlled trials (RCTs) with a large sample and sufficient follow-up period.