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21.
Emarene Kalaw Malcolm Lim Jamie R. Kutasovic Anna Sokolova Lucinda Taege Kate Johnstone James Bennett Jodi M. Saunus Colleen Niland Kaltin Ferguson Irma Gresshoff Mark Bettington Nirmala Pathmanathan Gary M. Tse David Papadimos Rajadurai Pathmanathan Gavin Harris Rin Yamaguchi Puay Hoon Tan Stephen Fox Sandra A. O’Toole Peter T. Simpson Sunil R. Lakhani Amy E. McCart Reed 《British journal of cancer》2020,123(11):1665
22.
Dry powder inhalers (DPIs) are gaining popularity for the delivery of drugs. A cost effective and efficient delivery device is necessary. Developing new DPIs by modifying an existing device may be the simplest way to improve the performance of the devices. The aim of this research was to produce a new DPIs using computational fluid dynamics (CFD). The new DPIs took advantages of the Cyclohaler® and the Rotahaler®. We chose a combination of the capsule chamber of the Cyclohaler® and the mouthpiece and grid of the Rotahaler®. Computer-aided design models of the devices were created and evaluated using CFD. Prototype models were created and tested with the DPI dispersion experiments. The proposed model 3 device had a high turbulence with a good degree of deagglomeration in the CFD and the experiment data. The %fine particle fraction (FPF) was around 50% at 60?L/min. The mass median aerodynamic diameter was around 2.8–4?μm. The FPF were strongly correlated to the CFD-predicted turbulence and the mechanical impaction parameters. The drug retention in the capsule was only 5–7%. In summary, a simple modification of the Cyclohaler® and Rotahaler® could produce a better performing inhaler using the CFD-assisted design. 相似文献
23.
You-Wen Tan 《World Journal of Meta-Analysis》2021,9(6):488-495
Nilotinib is a specific breakpoint cluster region-Abelson leukemia virus-tyrosine kinase inhibitor that is used as an effective first- or second-line treatment in imatinib-resistant chronic myelogenous leukemia (CML) patients. Hepatotoxicity due to nilotinib is a commonly reported side effect; however, abnormal liver function test (LFT) results have been reported in asymptomatic cases. When alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels are more than five-fold the upper limit of the normal (ULN) or when the serum total bilirubin level is more than three-fold the ULN, dose modification or discontinuation of nilotinib is recommended, resulting in decreased levels of hematological indicators in certain patients with CML. Nilotinib-induced hyperbilirubinemia typically manifests as indirect bilirubinemia without elevated ALT or AST levels. Such abnormal liver functioning is thus not attributed to the presence of a true histologic lesion of the liver. The underlying mechanism may be related to the inhibition of uridine diphosphate glucuronosyltransferase activity. Therefore, nilotinib dose adjustment is not recommended for this type of hyperbilirubinemia, and in the absence of elevated liver enzyme levels or presence of abnormal LFT findings, physicians should consider maintaining nilotinib dose intensity without modifications. 相似文献
24.
Feng He Yuanjun Ma Shi Li Haozhe Ren Qian Liu Xiaohua Chen Hui Miao Tao Ye Qian Lu Zuge Yang Tianle Li Xin Tong Hongxu Yang Mian Zhang Helin Wang Yazhou Wang Shibin Yu 《Journal of bone and mineral research》2022,37(5):1044-1055
Temporomandibular joint osteoarthritis (TMJOA) is a chronic degenerative disease for which the underlying mechanism still remains unclear. Compared with apoptosis and autophagy, necroptosis causes greater harm to tissue homeostasis by releasing damage-associated molecular patterns (DAMPs). However, the role of necroptosis and downstream key DAMPs in TMJOA is unknown. Here, rodent models of TMJOA were established by the unilateral anterior crossbite (UAC). Transmission electron microscopy (TEM) and immunohistochemistry of receptor interacting protein kinase 3 (RIPK3)/phosphorylation of mixed lineage kinase domain-like protein (pMLKL) were conducted to evaluate the occurrence of necroptosis in vivo. The therapeutic effects of blocking necroptosis were achieved by intra-articularly injecting RIPK3 or MLKL inhibitors and using RIPK3 or MLKL knockout mice. In vitro necroptosis of condylar chondrocyte was induced by combination of tumor necrosis factor alpha (TNFα), second mitochondria-derived activator of caspases (SMAC) mimetics and carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]- fluoromethylketone (z-VAD-fmk). The possible DAMPs released by necroptotic chondrocytes were screened by quantitative proteomics and blocked by specific antibody. Translucent cytosol, swollen organelles, and ruptured cell membranes, features of necroptosis, were frequently manifested in chondrocytes at the early stage of condylar cartilage degeneration in TMJOA, which was accompanied by upregulation of RIPK3/pMLKL. Inhibiting or knocking out RIPK3/MLKL significantly prevented cartilage degeneration. DAMPs released by necroptotic condylar chondrocytes, such as syndecan 4 (SDC4) and heat shock protein 90 (HSP90), were verified. Furthermore, blocking the function of SDC4 significantly attenuated the expression of TNFα in cartilage and synovium, and accordingly increased cartilage thickness and reduced synovial inflammation. Thus, the necroptotic vicious cycle of TNFα-SDC4-TNFα contributes to cartilage degeneration and synovitis, and can serve as a potential therapeutic target for treating TMJOA. © 2022 American Society for Bone and Mineral Research (ASBMR). 相似文献
25.
Growth Hormone Induces Recurrence of Infantile Hemangiomas After Apparent Involution: Evidence of Growth Hormone Receptors in Infantile Hemangioma 下载免费PDF全文
Naikhoba C. O. Munabi B.A. Qian Kun Tan H.S. Maria C. Garzon M.D. Gerald G. Behr M.D. Carrie J. Shawber Ph.D. June K. Wu M.D. 《Pediatric dermatology》2015,32(4):539-543
Infantile hemangiomas (IHs) are the most common benign tumor of infancy, characterized by a natural history of early proliferation in the first months of life to eventual involution during childhood, often with residual fibrofatty tissue. Once involution has been achieved, IHs do not typically recur. We present two cases of exogenous growth hormone therapy resulting in the recurrence of IHs in late childhood, supported by radiological, immunohistochemical, in vitro, and in vivo evidence. 相似文献
26.
27.
Hanna Lee Mary K. Tan Andrew T. Yan Paul Angaran Paul Dorian Claudia Bucci Jean C. Gregoire Alan D. Bell Martin S. Green Peter L. Gross Allan Skanes Charles R. Kerr L. Brent Mitchell Jafna L. Cox Vidal Essebag Brett Heilbron Krishnan Ramanathan Carl Fournier Shaun G. Goodman 《The Canadian journal of cardiology》2019,35(2):160-168
Background
Physicians treating nonvalvular atrial fibrillation (AF) assess stroke and bleeding risks when deciding on anticoagulation. The agreement between empirical and physician-estimated risks is unclear. Furthermore, the association between patient and physician sex and anticoagulation decision-making is uncertain.Methods
We pooled data from 2 national primary care physician chart audit databases of patients with AF (Facilitating Review and Education to Optimize Stroke Prevention in Atrial Fibrillation and Coordinated National Network to Engage Physicians in the Care and Treatment of Patients with Atrial Fibrillation Chart Audit) with a combined 1035 physicians (133 female, 902 male) and 10,927 patients (4567 female and 6360 male).Results
Male physicians underestimated stroke risk in female patients and overestimated risk in male patients. Female physicians estimated stroke risk well in female patients but underestimated the risk in male patients. Risk of bleeding was underestimated in all. Despite differences in risk assessment by physician and patient sex, > 90% of patients received anticoagulation across all subgroups. There was modest agreement between physician estimated and calculated (ie, CHADS2 score) stroke risk: Kappa scores were 0.41 (0.35-0.47) for female physicians and 0.34 (0.32-0.36) for male physicians.Conclusions
Our study is the first to examine the association between patient and physician sex influences and stroke and bleeding risk estimation in AF. Although there were differences in agreement between physician estimated stroke risk and calculated CHADS2 scores, these differences were small and unlikely to affect clinical practice; further, despite any perceived differences in the accuracy of risk assessment by sex, most patients received anticoagulation. 相似文献28.
29.
目的:观察理冲汤加减联合紫杉醇+卡铂(TC)方案治疗晚期卵巢癌的临床疗效及对患者血液流变学指标、免疫功能及肿瘤标志物水平的影响。方法:选取96例卵巢癌晚期患者,按随机数字表法分为对照组和观察组各48例。对照组给予TC方案治疗,观察组在对照组基础上给予理冲汤加减治疗,21 d为1个疗程,2组均治疗2个疗程。统计2组治疗前后的中医证候积分及治疗期间不良反应发生情况,检测血液流变学指标、T细胞亚群及肿瘤标志物水平,对比2组临床疗效。结果:治疗后,2组少腹包块、腹胀痛、面色无华及形体消瘦积分均较治疗前降低(P0.05),观察组上述4项中医证候积分均低于对照组(P0.05)。观察组疾病控制率77.08%,高于对照组的56.25%(P0.05)。观察组治疗有效率54.17%,对照组治疗有效率41.67%,2组比较,差异无统计学意义(P0.05)。治疗后,2组血液流变学指标(全血黏度高切、全血黏度中切、全血黏度低切、血浆黏度)水平均较治疗前降低(P0.05),观察组上述4项血液流变学指标水平均低于对照组(P0.05)。治疗后,观察组CD3+、CD4+、CD4+/CD8+水平均高于对照组(P0.05),CD8+水平低于对照组(P0.05)。治疗后,2组糖类抗原125 (CA125)、糖类抗原19-9 (CA19-9)、甲胎蛋白(AFP)含量均较治疗前降低(P0.05),观察组CA125、CA19-9、AFP含量均低于对照组(P0.05)。观察组白细胞减少发生率6.25%,低于对照组的27.08%(P0.05)。2组贫血、血小板减少、恶心呕吐、腹泻发生率比较,差异均无统计学意义(P0.05)。结论:理冲汤加减联合TC方案治疗晚期卵巢癌,可以有效改善患者的临床症状、血液流变学指标、免疫功能,降低肿瘤标志物水平,减少化疗产生的不良反应。 相似文献
30.
Han Wang Hui Ding Bo-wen Ouyang Zhenduo Yang Tan Zhong Hongming Fan Xingwu Zhong 《Eye (London, England)》2020,34(12):2328
ObjectivesTo investigate the effect of corneal stromal pocket irrigation after small-incision lenticule extraction (SMILE) on visual acuity, intraocular pressure (IOP), corneal parameters and complications after surgery.MethodsA total of 242 eyes of 121 patients undergoing SMILE were enrolled in this prospective controlled study, and it was designed for one eye to randomly undergo SMILE with balanced salt solution irrigation of the corneal stromal pocket, while the other eye was not. The uncorrected distance visual acuity (UDVA) and slit lamp examination were recorded at 1 hour, 1 day, 1 week, and 1 month. Postoperative corneal density, corneal biomechanical, corneal endothelial cell number, and anterior OCT images were compared at 1 day, 1 week, and 1 month.ResultsCompared with the nonirrigation group, the irrigation group showed significantly higher UDVA at 1 day postoperatively (P < 0.05), but there was no significant difference during the rest of the postoperative period (1 hour, 1 week, and 1 month). In addition, no significant differences were found in IOP, corneal density, corneal biomechanics, corneal endothelial cells, and corneal morphology. No visual decline or severe postoperative complications were found in the patients in this study.ConclusionsInterlamellar irrigation did not affect IOP, corneal parameters, morphology, complications, or UDVA at 1 hour, 1 week, and 1 month after the operation, but it may promote UDVA 1 day after the operation.Subject terms: Refractive errors, Outcomes research, Surgery 相似文献