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1.
《Vaccine》2022,40(34):4933-4941
Subunit influenza vaccine only formulated with surface antigen proteins has better safety profiles relative to split-virion influenza vaccine. Compared to the traditional quadrivalent split-virion influenza vaccine, a novel quadrivalent subunit influenza vaccine is urgently needed in China. We completed a phase 3, randomized, double-blind, active-controlled, non-inferiority clinical study at two sites in Henan Province, China. Eligible volunteers were split into four age cohorts (3–8 years, 9–17 years, 18–64 years, and ≥ 65 years, based on their dates of birth) and randomly assigned (1:1) to the subunit and the split-virion ecNAIIV4 groups. All volunteers were intramuscularly administered a single vaccine dose at baseline, and children aged 3–8 years received a boosting dose at day 28. And the immune response was evaluated by measuring hemagglutinin-inhibition antibody titers against the four vaccine strains in blood samples. Safety profiles had nonsignificant differences between the study groups in ≥ 3 years cohort. Most adverse reactions post-vaccination, both local and systemic, were mild to moderate and resolved within 3 days. And no serious adverse events occurred. The immunogenicity of the trial vaccine was non-inferior to the comparator. Further, a two-dose vaccine series can provide better seroprotection than that of a one-dose series in children aged 3–8 years, with clinically acceptable safety profiles.Clinical Trials Registration. ChiCTR2100049934. 相似文献
2.
Naveen Pemmaraju MD Jacqueline S. Garcia MD Andrew Perkins MBBS PhD Jason G. Harb PhD Andrew J. Souers PhD Michael E. Werner PhD Christopher M. Brown PhD Francesco Passamonti MD 《Cancer》2023,129(22):3535-3545
Myelofibrosis is a heterogeneous myeloproliferative neoplasm characterized by chronic inflammation, progressive bone marrow failure, and hepatosplenic extramedullary hematopoiesis. Treatments like Janus kinase inhibitor monotherapy (e.g., ruxolitinib) provide significant spleen and symptom relief but demonstrate limited ability to lead to a durable disease modification. There is an urgent unmet medical need for treatments with a novel mechanism of action that can modify the underlying pathophysiology and affect the disease course of myelofibrosis. This review highlights the role of B-cell lymphoma (BCL) protein BCL-extra large (BCL-XL) in disease pathogenesis and the potential role that navitoclax, a BCL-extra large/BCL-2 inhibitor, may have in myelofibrosis treatment. 相似文献
3.
杨姗 《世界科学技术-中医药现代化》2022,24(9):116-125
目的 优化大孔吸附树脂分离纯化血人参总黄酮的工艺条件,研究血人参总黄酮对酪氨酸酶的抑制作用。方法 以吸附率、解吸率等为考察指标,采用静态吸附-解吸试验对6种不同型号的大孔吸附树脂进行筛选,优选最佳的树脂型号。采用单因素试验考察上样液pH、上样液浓度、上样体积、上样体积流量、洗脱溶剂、洗脱液体积流量、洗脱剂体积对血人参总黄酮纯化的影响,确定最佳纯化工艺;以L-酪氨酸、L-多巴为底物,测定血人参总黄酮对酪氨酸单酚酶和二酚酶的抑制作用,并对其抑制机理和抑制类型进行分析。结果 AB-8型大孔吸附树脂对血人参总黄酮的分离纯化效果最好。最佳纯化工艺参数为:上样液pH为4、上样体积为70 mL(4.7 BV)、上样体积流量为1 mL·min-1、上样液浓度为5.38 mg·mL-1、洗脱溶剂为70%乙醇、洗脱剂体积流量为3 mL·min-1、洗脱剂体积为120 mL(8 BV),血人参总黄酮对酪氨酸单酚酶和二酚酶均有抑制作用,其最大半数抑制浓度分别为88.78 mg·L-1和36.46 mg·L-1,对二酚酶的抑制类型为可逆非竞争性抑制。结论 AB-8型大孔吸附树脂可用于纯化血人参总黄酮,纯化后血人参总黄酮的纯度为46.01%,建立的工艺条件稳定可靠。纯化后的血人参总黄酮对酪氨酸酶有抑制作用,抑制类型为可逆非竞争性抑制。 相似文献
4.
Michael Mark Dirk Klingbiel Ulrich Mey Ralph Winterhalder Christian Rothermundt Silke Gillessen Roger von Moos Michael Pollak Gabriela Manetsch Räto Strebel Richard Cathomas 《Clinical genitourinary cancer》2019,17(2):e323-e328
Background
There is evidence linking metformin to improved prostate cancer–related outcomes.Patients and Methods
Twenty-five men with metastatic castration-resistant prostate cancer and prostate-specific antigen (PSA) progression while receiving treatment with abiraterone from 3 Swiss centers were included in this single-arm phase 2 trial between November 2013 and September 2016. Metformin was added to abiraterone continuously at 1000 mg twice daily in uninterrupted 4-week cycles. The primary end point was the absence of disease progression at 12 weeks (PFS12). The Fleming single-stage design was applied. With a 5% significance level and 80% power, 25 patients were required to test PFS12 ≤ 15% (H0) compared to ≥ 35% (H1). Secondary end points included toxicity and safety issues. The study was registered at ClinicalTrials.gov (NCT01677897).Results
The primary end point PFS12 was 12% (3 of 25 patients) (95% confidence interval, 3-31). Most patients had PSA progression, almost half had radiographic progression, but only 1 patient had symptomatic progression. Eleven (44%) of 25 patients had grade 1 and 2 patients each grade 2 (8%) or grade 3 (8%) gastrointestinal toxicity (nausea, diarrhea, loss of appetite). One patient discontinued treatment at week 5 because of intolerable grade 3 diarrhea.Conclusion
The addition of metformin to abiraterone for patients with metastatic castration-resistant prostate cancer and PSA progression while receiving abiraterone therapy does not affect further progression and has no meaningful clinical benefit. A higher-than-expected gastrointestinal toxicity attributed to metformin was observed. 相似文献5.
目的:初步探讨mTOR抑制剂AZD2014对肝癌细胞的增殖抑制作用及其机制。方法:先采用CCK-8法检测不同浓度的AZD2014(10、100、500、1 000 nmol/L)对肝癌细胞增殖的作用,再分别采用荧光定量PCR和Western blot法检测肝癌细胞中含植物同源结构和环指域泛素样蛋白1(UHRF1)mRNA和蛋白的表达水平。结果:细胞增殖实验结果显示,10、100、500、1 000 nmol/L的AZD2014均可显著抑制肝癌细胞的增殖能力,抑制程度与其浓度呈正相关(P < 0.05);荧光定量PCR和Western blot检测结果显示,500和1 000 nmol/L的AZD2014可显著降低肝癌细胞内UHRF1 mRNA及蛋白的表达水平。结论:AZD2014可能通过抑制肝癌细胞内UHRF1的表达水平来抑制肝癌细胞的增殖能力。 相似文献
6.
《药学学报(英文版)》2020,10(5):895-902
Seven indole alkaloid glycosides containing a 1′-(4″-hydroxy-3″,5″-dimethoxyphenyl)ethyl unit (1–7) were isolated from an aqueous extract of Isatis indigotica leaves (da qing ye). Their structures were determined by spectroscopic data analysis combined with enzymatic hydrolysis as well as comparison of their experimental CD (circular dichroism) and calculated ECD (electrostatic circular dichroism) spectra. Based on analysis of and/or Cotton effect (CE) data of 1–7, two simple roles to assign location and/or configuration of β-glycopyranosyloxy and 1′-(phenyl)ethyl units in the indole alkaloid glycosides are proposed. Stereoselectivity in plausible biosynthetic pathways of 1–7 is discussed. Compounds 3 and 4 and their mixture in a 3:2 ratio showed activity against KCNQ2 in CHO cells. The mixture of 5 and 6 (3:2) exhibited antiviral activity against influenza virus H1N1 PR8 with IC50 64.7 μmol/L (ribavirin, IC50 54.3 μmol/L), however, the individual 5 or 6 was inactive. Preliminary structure–activity relationships were observed. 相似文献
7.
《Clinical genitourinary cancer》2020,18(3):e209-e216
BackgroundFirst-line PD-inhibition in cisplatin-ineligible patients with locally advanced or metastatic urothelial cancer represents a novel clinical setting, with uncertainty concerning second-line outcomes. Specifying second-line treatment and outcomes will provide guidance in this new sequence. We performed a retrospective chart review to document the outcomes of these patients treated at our institution.Patients and MethodsOur cohort consisted of 43 patients with advanced urothelial cancer receiving first-line checkpoint inhibition. Baseline factors, programmed death-ligand 1 (PD-L1) status, treatments, and outcomes during and beyond the first line were obtained. Response was scored using Response Evaluation Criteria in Solid Tumors, version 1.1 criteria. Log rank tests were used to compare outcomes in prognostic subgroups, and outcome associations with PD-L1 status were analyzed with Fisher exact tests.ResultsA total of 43 patients received first-line atezolizumab or pembrolizumab from June 2014 until June 2018. The median age was 76.8 years, and the population was 74% male, with 60% having visceral metastases. Reasons for cisplatin ineligibility were Eastern Cooperative Oncology Group performance status 2%, 30%; renal insufficiency, 44%, and both, 21%. First-line objective response rate (ORR) was 30%, and complete response was 14%. The median overall survival was 11.7 months. Of 29 patients progressing, 17 received second-line treatment (most commonly, gemcitabine/carboplatin [10 patients]). The second-line response rate was 33%, and the ORR was 11%. The second-line median overall survival was 6.2 months. No association was found between PD-L1 status and outcomes.ConclusionOutcomes with first-line immunotherapy are consistent with historical outcomes. The ORR after first-line checkpoint inhibition falls short of historical comparators; however, the response rate compares favorably to those of chemotherapies used in previous second-line regimens. The older age and poorer performance status may have contributed to second-line outcomes. 相似文献
8.
目的:对妇科肿瘤患者的组织因子(tissue factor,TF)、组织因子抑制物(tissue factor pathway inhibitor,TFPI)的水平含量进行测定,探究其与妇科恶性肿瘤术后深静脉血栓形成的关系。方法:选取2013年1月至2015年1月我院收治的73例妇科恶性肿瘤患者作为本次研究的对象,选取同期于我院接受体检的50例健康妇女作为对照组,采用ELISA法对所有研究对象的TF、TFPI抑制物水平进行检测,同时分析二者与深静脉血栓形成的关系。结果:研究中有9例患者在术后发生深静脉血栓,其中宫颈癌患者4例,子宫内膜癌患者3例,卵巢癌患者2例。全部类型的妇科恶性肿瘤患者的血浆TF、血浆TFPI-1水平以及TFPI活性均显著高于对照组(P<0.05);对照组的TFPI-1水平显著低于有、无深静脉血栓组,而TF水平显著低于有深静脉血栓组(P<0.05);无深静脉血栓组的TF、TFPI-1水平均显著低于有深静脉血栓组(P<0.05)。结论:妇科肿瘤术后深静脉血栓形成的患者血浆TF、TFPI-1水平显著增高,可将TF、TFPI-1作为预测深静脉血栓形成的重要检测指标。 相似文献
9.
目的研究羌活Notopterygium incisum的香豆素类成分及其抗炎活性。方法采用硅胶、HPLC等柱色谱方法进行分离纯化,通过质谱、核磁共振波谱数据鉴定化合物的结构;采用脂多糖(LPS)诱导的小鼠巨噬细胞RAW 264.7炎症反应模型,考察羌活中香豆素类成分对炎症反应模型一氧化氮(NO)生成的影响。结果从羌活甲醇提取物分离得到24个香豆素类化合物,分别鉴定为异欧前胡素(1)、川白芷素(2)、补骨脂素(3)、香柑内酯(4)、茵陈素(5)、欧芹酚(6)、5-去氢羌活醇(7)、环氧脱水羌活醇(8)、7″-O-甲基异羌活醇(9)、佛手柑素(10)、7-异戊烯氧基-6-甲氧基-香豆素(11)、栓翅芹烯醇(12)、羌活醇(13)、去甲呋喃羽叶芸香素(14)、异羌活醇(15)、蛇床夫内酯(16)、6-异戊烯氧基伞形花内酯(17)、紫花前胡苷元(18)、异虎耳草素(19)、紫花前胡苷(20)、前胡苷V(21)、前胡苷I(22)、印枳苷元-11-O-β-D-吡喃葡萄糖基-(1→6)-β-D-吡喃葡萄糖苷(23)、羌活苷(24)。化合物7~10、13和15抑制LPS诱导的RAW 264.7细胞NO生成活性最强,最大半数抑制浓度(IC_(50))值为8.50~35.12μmol/L。结论化合物7为新的天然产物,化合物17为首次从羌活中分离得到;C-5位上具有多烯烃结构的香豆素抑制LPS诱导的RAW 264.7细胞NO生成活性较强。 相似文献
10.
《药学学报(英文版)》2020,10(2):327-343
Our recent studies demonstrated that the natural product nobiletin (NOB) served as a promising multidrug resistance (MDR) reversal agent and improved the effectiveness of cancer chemotherapy in vitro. However, low aqueous solubility and difficulty in total synthesis limited its application as a therapeutic agent. To tackle these challenges, NOB was synthesized in a high yield by a concise route of six steps and fourteen derivatives were synthesized with remarkable solubility and efficacy. All the compounds showed improved sensitivity to paclitaxel (PTX) in P-glycoprotein (P-gp) overexpressing MDR cancer cells. Among them, compound 29d exhibited water solubility 280-fold higher than NOB. A drug-resistance A549/T xenograft model showed that 29d, at a dose of 50 mg/kg co-administered with PTX (15 mg/kg), inhibited tumor growth more effective than NOB and remarkably increased PTX concentration in the tumors via P-gp inhibition. Moreover, Western blot experiments revealed that 29d inhibited expression of NRF2, phosphorylated ERK and AKT in MDR cancer cells, thus implying 29d of multiple mechanisms to reverse MDR in lung cancer. 相似文献