甲磺酸伊马替尼联合VDLD化疗方案治疗急性淋巴细胞白血病患儿的长期随访研究

目的探究甲磺酸伊马替尼联合VDLD化疗方案治疗急性淋巴细胞白血病(ALL)患儿的应用价值。方法选取2015年5月~2018年6月收治的74例ALL患儿,按照治疗方案不同分组。对照组(37例)实施VDLD方案治疗,联合组(37例)实施甲磺酸伊马替尼+VDLD化疗方案治疗。对比两组疗效、不良反应发生率、随访1年无复发生存率(RFS)及治疗前、治疗2个疗程后血清B淋巴细胞刺激因子(BAFF)、增殖诱导配体(APRIL)水平。结果联合组总有效率(91.89%)高于对照组(72.97%)(P<0.05);联合组治疗2个疗程后血清BAFF、APRIL水平低于对照组(P<0.05);两组不良反应发生率、随访1年RFS对比无显著差异(P>0.05)。结论甲磺酸伊马替尼联合VDLD化疗方案治疗ALL,疗效确切,能显著降低血清BAFF、APRIL水平,且安全性高。     

In Vitro and in Vivo Evaluation of Whole and Half Tablets of Sustained-Release Adinazolam Mesylate

The mechanism of release from sustained-release adinazolam mesylate tablets was assessed by the Higuchi equation and by analysis of drug release profiles through 60% released using the Peppas equation. Computed values of the diffusional exponent, n, ranged from 0.59 to 0.66. Values of n in this range are consistent with a mixed mechanism of release, with diffusion of drug through the hydrated polymer matrix and relaxation of this matrix being the principal processes controlling release. The rate of in vitro drug release was increased for half tablets relative to whole tablets and is attributed to an increase in the surface to volume ratio of half tablets of about 16%. This increase in surface-to-volume ratio of half tablets was reflected by an increase in the constant, k, from the Peppas equation of 20–23% and by an increase in the slope of Higuchi plots of 12–18% for four lots of tablets. In vivo/in vitro relationships from two bioavailability studies were thoroughly evaluated. Using either a linear or a quadratic relationship, an in vivo/in vitro correlation exists for sustained-release adinazolam mesylate tablets.     

新药甲磺酸帕珠沙星的手性拆分

目的：建立新药甲磺酸帕珠沙星手性拆分的方法。方法：运用AD手性柱法和流动相添加剂法，考察了不同条件下对分离的影响。结果：运用这两种方法，甲磺酸帕珠沙星都可以达到基线分离，相同条件下，柱温越低，拆分因子越大。结论：在分离甲磺酸帕珠沙星时，流动相添加剂法要优于手性柱法。     

甲磺酸帕珠沙星注射液治疗急性细菌性感染有效性和安全性的多中心临床研究

目的评价甲磺酸帕珠沙星注射液治疗急性细菌性呼吸系统、泌尿生殖系统感染的有效性、安全性。方法采用随机单盲平行对照多中心试验方法。选择急性细菌性呼吸系统、泌尿生殖系统感染患者213例，可评价病例209例，随机编人试验组或对照组。试验组101例．每日1次给予甲磺酸帕珠沙星注射液300mg，iv，gtt，bid；对照组108例，每日1次给予加替沙星注射液200mg，iv，gtt，bid。疗程7～10d。结果甲磺酸帕珠沙星组、加替沙星组有效率分别为94．06％（95／101）和90．74％（98／108）；痊愈率分别为67．33％（68／101）和70．37％（76／108）；细菌清除率分别为94．62％（88／93）和93．62％（88／94）；不良反应发生率分别为7，69％（8／104）和5．50％（6／109）。两组有效性、安全性相似（P〉0．05）。结论甲磺酸帕珠沙星注射液治疗急性细菌性呼吸系统、泌尿生殖系统感染有效、安全，与加替沙星相当。     

A long-term time course of colorimetric assessment of the effects of imatinib mesylate on skin pigmentation: a study of five patients

BACKGROUND: Imatinib mesylate (IM), the first-line treatment of chronic myeloid leukaemia (CML), is a tyrosine kinase inhibitor that targets those proteins involved in BCR-ABL signal transduction in CML, c-kit (KIT) and platelet-derived growth-factor (PDGFR) receptor. The use of IM has been associated with cutaneous reactions. In the last 2 years numerous studies have focused the attention on hypopigmentations, depigmentations and photosensitivity developing after the initiation of IM therapy. OBJECTIVE: The aim of this study is to evaluate the effects of IM therapy on the skin pigmentation of five patients affected by CML. METHODS: Skin pigmentation measurements were performed with a Minolta CR-200 Chromameter. results: All the studied patients show the gradual lightening of the skin on unexposed areas over the treatment with IM. In particular, this explorative colorimetric study indicates the association between IM and skin depigmentation with a significant increase of luminance value (L*) (P = 0.001) and a significant decrease of the pigmentation value (b*) (P = 0.028). CONCLUSION: Even if we do not know the clinical significance of the skin depigmentation caused by IM, the regulatory role of KIT and its ligand stem cell factor in melanocyte development and survival seems to suggest an objective mechanism of action for IM in the pathogenesis of this cutaneous depigmentation.     

胃肠间质瘤的CT诊断及治疗评价

目的:探讨胃肠间质瘤(GIST)的CT表现及分子靶向药物甲磺酸伊马替尼(STI571)对胃肠间质瘤疗效的CT评价。方法:选择经手术及病理证实的胃肠间质瘤病例32例进行回顾性分析。对19例接受STI571治疗者进行定期CT检查随访,观察病灶大小、形态及密度变化,评价药物疗效。结果:32例GIST中,发生于胃部的18例,小肠11例,肠系膜1例,直肠2例。①CT特征:恶性度较高的胃肠间质瘤CT表现为:肿块相对较大,密度不均,肿瘤中央坏死及囊变多见;肿瘤边缘多不光整,可呈分叶状。增强扫描肿瘤呈不均匀强化;少数巨大肿瘤密度较低,极少数可见高密度出血及钙化灶。良性GIST体积较小,密度均匀,肿瘤坏死及囊变少见,病灶边缘光整,增强扫描多呈均匀强化;②19例接受STI571治疗者定期CT检查疗效评价为(肿瘤缩小):疗效达PR(部分缓解)者9例,占47.4%,疗效为SD(疾病稳定)者8例,占42.1%,病灶进展(PD)者2例,占10.5%。术后2年内复发及转移者19例。结论:①螺旋CT扫描是诊断胃肠间质瘤最常用和最有价值的影像检查手段,其定位诊断率达81%以上;②应用CT扫描观察测量病灶变化是评价药物(STI571)治疗胃肠间质瘤疗效最重要和最直接的方法之一;对指导临床治疗具有重要意义。     

Laparoscopic resection for a large gastrointestinal stromal tumor (GIST) with diaphragm invasion following preoperative imatinib treatment: A case report

IntroductionNeoadjuvant imatinib for large GISTs may prevent tumor rupture and the need for extended surgery by reducing tumor size. In this study, we present a case of large gastric GIST with diaphragm invasion, due to the patient receiving laparoscopic resection following preoperative imatinib treatment.Presentation of caseA 72-year-old woman was hospitalized with left hypochondriac pain for a month. Examinations revealed a large heterogeneous gastric mass measuring 80 mm in size, arising from the greater curvature of the corpus. The mass invaded the left thoracic diaphragm. Treatment with imatinib at an initial dosage of 400 mg/day was initiated. After a further two months of follow-up, the lesion had sustained reduction to 50 mm in size, however, the invasion to the diaphragm remained. The patient eventually underwent laparoscopic partial gastrectomy and partial resection of the diaphragm with curative intent. Adjuvant chemotherapy was initiated at one month after the surgery, however, was discontinued due to nausea. After one-year follow-up, no recurrence was noted.DiscussionNeoadjuvant imatinib may shrink tumor size remarkably and prevent tumor rupture during surgery, and thus lead to increased rates of complete resection. To date, several publications have directly compared the oncologic results between laparoscopic and open resection for GISTs. In the present case, the tumor was movable, and moderately fixed on diaphragm. It was favorable condition for laparoscopic surgery.ConclusionsThis is the first report of a large gastric GIST invading the diaphragm that was successfully treated by laparoscopic resection after tumor reduction by neoadjuvant imatinib.     

Anti-SARS-CoV-2 activity of targeted kinase inhibitors: Repurposing clinically available drugs for COVID-19 therapy

Coronavirus disease 2019 (COVID-19) remains a major public health concern, and vaccine unavailability, hesitancy, or failure underscore the need for discovery of efficacious antiviral drug therapies. Numerous approved drugs target protein kinases associated with viral life cycle and symptoms of infection. Repurposing of kinase inhibitors is appealing as they have been vetted for safety and are more accessible for COVID-19 treatment. However, an understanding of drug mechanism is needed to improve our understanding of the factors involved in pathogenesis. We tested the in vitro activity of three kinase inhibitors against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including inhibitors of AXL kinase, a host cell factor that contributes to successful SARS-CoV-2 infection. Using multiple cell-based assays and approaches, gilteritinib, nintedanib, and imatinib were thoroughly evaluated for activity against SARS-CoV-2 variants. Each drug exhibited antiviral activity, but with stark differences in potency, suggesting differences in host dependency for kinase targets. Importantly, for gilteritinib, the amount of compound needed to achieve 90% infection inhibition, at least in part involving blockade of spike protein-mediated viral entry and at concentrations not inducing phospholipidosis (PLD), approached a clinically achievable concentration. Knockout of AXL, a target of gilteritinib and nintedanib, impaired SARS-CoV-2 variant infectivity, supporting a role for AXL in SARS-CoV-2 infection and supporting further investigation of drug-mediated AXL inhibition as a COVID-19 treatment. This study supports further evaluation of AXL-targeting kinase inhibitors as potential antiviral agents and treatments for COVID-19. Additional mechanistic studies are needed to determine underlying differences in virus response.     

氢化麦角碱治疗血管性痴呆30例观察

应用氢化麦角碱治疗反复发作性脑梗塞(病程>1年)最终导致不同程度痴呆病人30例,并与常规应用维脑路通治疗同期同类病人做对照。结果治疗组与对照组显效率进行比较存在显著差异,同时观察到此药的一些少见的副作用,经减量可消失,不影响正规疗程,故此药疗效肯定安全,不失为临床推广应用。