Screening and identification of 3-aryl-quinolin-2-one derivatives as antiviral agents against influenza A

Quinolin-2-one represents an important and valuable chemical motif that possesses a wide variety of biological activities; however, the anti-influenza activities of quinolin-2-one-containing compounds were rarely reported. Herein, we describe the screening and identification of 3-aryl-quinolin-2-one derivatives as a novel class of antiviral agents. The 3-aryl-quinolinone derivatives were synthesized via an efficient copper-catalyzed reaction cascade that we previously developed. Using this synthetic method, preliminary structure–activity relationships of this scaffold against the influenza A virus infection were systematically explored. The most potent compound 34 displayed IC₅₀ values of 2.14 and 4.88 μM against the replication of H3N2 (A/HK/8/68) and H1N1 (A/WSN/33) strains, respectively, without apparent cytotoxicity on MDCK cells. We further demonstrated that 27 and 34 potently inhibited the plaque formation of the IAV, rendering this scaffold attractive for pursuing novel anti-influenza agents.     

古溪针刀辅助鲑降钙素治疗老年骨质疏松症的临床疗效分析

目的分析古溪针刀辅助鲑降钙素治疗老年骨质疏松症的临床疗效。方法将我院收治的66例老年骨质疏松症患者随机分为观察组33例,对照33例。观察组患者行古溪针刀辅助鲑降钙素联合钙剂治疗,对照组患者行鲑降钙素联合钙剂治疗。两组患者及治疗6个月、12个月后均测量骨密度、评价疼痛控制情况、生活能力改善情况等。结果对照组疼痛、日常生活能力、腰椎及左髋关节骨密度均在治疗后6、12个月有所改善,但与观察组对比发现,观察组治疗后6个月疼痛得到明显缓解(P0.05),日常生活能力、腰椎及左髋关节骨密度得到明显提高(P0.05),且在治疗12个月后日常生活能力、腰椎及左髋关节骨密度仍在不断改善(P0.05)。结论古溪针刀辅助鲑降钙素治疗的临床疗效显著,能快速缓解老年骨质疏松症患者疼痛,并有效提高其骨密度和日常生活能力,控制骨量的的减少,避免发生病理性骨折。     

Recent advances in the synthesis of fluorinated hydrazones

Fluorinated compounds are widely used in pharmaceuticals, agrochemicals, and materials. As an important branch of fluorinated compounds, the introduction of fluorinated hydrazones remains unexplored due to the lack of convenient methods. However, as a powerful platform for generation of various fluorinated pyrazole species and diverse nitrogen-containing compounds, fluorinated hydrazones have been extensively studied in recent years. In this review, we highlight most of the important developments in fluorinated hydrazone synthesis.

Fluorinated compounds are widely used in pharmaceuticals, agrochemicals, and materials.     

可乐定对原代培养大鼠皮质神经元氧糖剥夺损伤的保护作用

目的：研究可乐定对原代培养大鼠皮质神经元氧糖剥夺( OGD)损伤的保护作用。方法取培养8 d的皮质神经元,分为正常对照组、模型对照组、可乐定(1.0,3.0,10.0μmol·L-1)预处理组。神经元氧糖剥脱损伤模型通过化学性缺氧、孵育液缺糖的方法建立。神经元损伤程度采用噻唑蓝( MTT)染色法和检测乳酸脱氢酶( LDH)的释放量来进行评价,观察预给予可乐定(1.0,3.0,10.0μmol·L-1)对神经元损伤的保护作用。结果显微镜下,正常对照组细胞密集,胞体饱满,边缘光滑,有较强折光性;神经元存活率(100.00±32.12)％,LDH释放比率(100.00±37.51)％。模型对照组细胞核固缩,细胞膜不完整,折光性差,MTT染色吸光度值明显降低,神经元存活率(53.61±7.62)％,LDH释放量显著增加,释放率为(166.07±9.65)％。可乐定(1.0,3.0,10μmol·L-1)预处理可明显逆转ODG损伤所致细胞形态的改变,剂量依耐性升高MTT染色吸光度值,神经元存活率分别为(67.53±10.54)％,(71.50±9.79)％和(87.48±5.29)％,同时可明显降低LDH的释放量,释放率分别为(136.45±25.72)％,(130.92±24.94)％和(121.63±32.68)％。结论可乐定对原代培养大鼠皮质神经元ODG损伤具有良好的保护作用。     

三叉神经鞘瘤的临床分型及其手术疗效分析

目的探讨三叉神经鞘瘤的临床分型及其手术疗效。方法回顾性分析2017年1月至2019年11月首都医科大学附属北京天坛医院神经外科手术治疗的51例(包括少见部位和肿瘤最大径≥6 cm的患者)三叉神经鞘瘤患者的临床资料。根据Yoshida和Kawase的MPE分型分别采用颞下经岩前入路(30例)、经额颞断颧弓入路(12例)、经额眶颧人路(4例)、经枕下乙状窦后入路(2例)、经乙状窦前入路(2例)和经远外侧入路(1例)。术后随访MRI、新发症状及脑神经功能的恢复情况。结果51例患者中,肿瘤全切除46例(90.2%),近全切除4例,大部切除1例,无手术死亡病例。其中6例中线-鞍上扩展亚型的患者,肿瘤全切除2例,近全切除3例,大部切除1例。7例肿瘤直径≥6 cm的患者中,肿瘤全切除6例,肿瘤卒中1例;其中4例行游离脂肪填塞结合颅底硬膜缝合的颅底重建。51例患者的随访时间为(20.2±2.7)个月(3~38个月)。24例术前面部麻木的患者中,12例(50.0%)随访期间仍存在重度三叉神经麻搏表现。51例患者中,有13例(25.5%)术后新发三叉神经功能异常的患者中,7例随访期间遗留轻度三叉神经麻搏症状。其余脑神经症状较术前有所恢复,并且术后新发神经功能障碍者大多恢复正常。6例中线-鞍上扩展亚型的患者术后神经功能恢复较差。结论三叉神经鞘瘤在MPE分型的基础上可增加中线-鞍上扩展亚型,该亚型相对少见,但其临床表现具有特征性,手术全切除困难。手术对于改善三叉神经鞘瘤面部麻木作用有限,术前伴有面部麻木者三叉神经功能预后较差。     

眶上外入路联合腰大池引流与翼点入路治疗急性期前循环动脉瘤破裂伴发脑积水的临床对比分析

目的对比眶上外入路联合腰大池引流与翼点入路治疗急性期颅内前循环动脉瘤破裂伴发脑积水的手术治疗效果。 方法选择自2017年1月至2019年6月四川省医学科学院·四川省人民医院神经外科收治的48例急性期颅内前循环动脉瘤破裂伴发脑积水患者作为研究对象,依据手术方式分为2组,每组24例。观察组采用眶上外入路联合腰大池引流术式,对照组采用翼点入路组。评估2组患者的临床指标变化与手术效果,根据简易精神评价量表评价患者术后记忆力、定向力、回忆能力、语言能力。 结果观察组的手术时间和住院时间较对照组短,差异具有统计学意义（P<0.05）。观察组的术中出血量与对照组比较,差异无统计学意义（P>0.05）。观察组术中颞浅动脉损伤和脑组织牵拉损伤较对照组少,颞肌萎缩和术后脑积水的发生率较对照组低,差异具有统计学意义（P<0.05）。观察组患者术后记忆力、定向力、回忆能力、语言能力与对照组比较,差异均具有统计学意义（P<0.1）;注意力和计算力与对照组比较,差异无统计学意义（P>0.1）。 结论眶上外入路联合腰大池引流治疗急性期颅内前循环动脉瘤破裂伴发脑积水,能有效减少术中脑挫伤、术后并发症,有利于患者快速康复,提高患者生存质量。     

黑色先端帽联合窄带光成像在结肠镜检查中的作用

目的评估黑色先端帽辅助结肠镜联合窄带光成像（narrow band imaging,NBI）技术对腺瘤/息肉检出效能的影响。方法连续纳入2016年10月—2018年10月行结肠镜检查的患者,采用随机数字表法分为黑色先端帽组和对照组,黑色端帽组采用黑色先端帽辅助结肠镜联合NBI技术,对照组采用标准白光结肠镜,比较两组的息肉检出率、腺瘤检出率等指标,并进行亚组分析。结果共1 000例患者纳入本研究（每组500例）,黑色先端帽组和对照组近端结肠腺瘤检出率分别为24.2%(121/500)和17.2%(86/500),近端结肠息肉检出率分别为28.8%(144/500)和21.4%(107/500),平均腺瘤检出数分别0.41±0.94和0.26±0.68,平均息肉检出数为0.63±1.16和0.40±0.85,差异均有统计学意义（P均<0.05）,但该联合技术对于远端结直肠病变的检出率相较对照组无明显优势。结论黑色先端帽辅助结肠镜联合NBI能显著提高近端结肠腺瘤和息肉等微小病变的检出效能。     

Surgical resection of large and giant petroclival meningiomas via a modified anterior transpetrous approach

The authors describe a modified anterior transpetrous approach (ATPA) for the surgical resection of 21 cases of petroclival meningiomas (PCMs). Briefly, a curved periauricular skin incision was used. The cerebellar tentorium and the dura on the petrous apex were coagulated and incised to expose the petrous apex bone fully. The drilling of the petrous apex bone was performed subdurally and began internally from the trigeminal impression, not exceeding 1.5 cm laterally, not exceeding 6 mm from the posterior edge of the petrous ridge, and not exceeding 8 mm in depth from the surface of the petrous bone. The tumors were removed totally in 12 (57.1 %) cases, subtotally in 8 (38.1 %) cases, and partially in 1 (4.8 %) case. The transient neurological deficit includes mild oculomotor nerve palsy in three cases, abducens nerve palsy in six cases, language disorder in three cases, and mild hemiplegia in two cases. Facial numbness became worse postoperatively in six patients, and only two patients improved at 6 months after surgery. No death occurred in this series. The modified ATPA is an efficient treatment alterative for large or giant PCMs located at the medial and superior internal acoustic meatus with relatively low risk of complications.     

Clinical features and management of intracranial subependymomas in children

Subependymoma is a rare low-grade glioma of the central nervous system that occurs most commonly in middle-aged and elderly men and rarely in children. Only a few paediatric patients with subependymomas have been reported. The authors retrospectively analysed five paediatric patients (4 males and 1 female; mean age 8.6 years; age range 5–13 years) at a single institute from July 1998 to April 2009 and summarised the clinical characteristics and management of paediatric intracranial subependymoma. The most common symptom in these five paediatric patients with subependymoma was intracranial hypertension. The tumours were located in the fourth ventricle in two patients, in the fourth ventricle with extension to the cerebellopontine angle (CPA) in one patient; in the right CPA exclusively in one patient, and intraparenchymally in the left parietal lobe in one patient, the latter two of which are rare locations for subependymoma. Surgery was performed on all five patients. The surgical approach was selected as appropriate for the tumor location. Total resection was achieved in three patients, and subtotal resection in two. All five patients had good outcomes without recurrence. We conclude that surgery is the optimal therapy for paediatric patients with intracranial subependymoma.     

外周血淋巴细胞和单核细胞比值对儿童霍奇金淋巴瘤预后的意义

目的成人霍奇金淋巴瘤(HL)研究显示外周血淋巴细胞绝对值与单核细胞绝对值的比值(absolute lymphocyte count/absolute monocyte count ratio,LMR)具有预后意义。而在儿童HL中鲜有研究,本研究主要探讨LMR在儿童HL中的预后价值。方法回顾性分析中山大学肿瘤防治中心从1998年1月-2013年10月收治的107例初诊年龄18岁儿童青少年HL的临床资料,收集和分析患者初诊时的外周血淋巴细胞绝对值(absolute lymphocyte count,ALC)、淋巴细胞百分比(1ymphocyte percentage,LYM%)和单核细胞绝对值(absolute monocyte count,AMC)等数据,通过SPSS中受试者工作特征曲线(receiver operating characteristic curve analysis,ROC)获得淋巴细胞绝对值与单核细胞绝对值比值LMR、LYM%、AMC与及ALC的最佳临界值,在该临界值上敏感度与精确度都达到最大值。再进行单因素和多因素分析其与预后的关系。结果 107例儿童HL纳入分析,男80例,女27例,中位年龄10(2~18)岁。Ⅰ期5例,Ⅱ期50例,Ⅲ期33例,Ⅳ期19例。所有患者采用ABVD为基础的化疗方案±放疗。107例患者LMR的最佳临界值是2.15(P=0.006),LMR/≥2.15患者66例,LMR2.15患者41例。中位随访时间51.2(7~204)个月。全组5年EFS和OS分别为82.3%和96.7%。LMR≥2.15组和LMR2.15组患者5年EFS分别为87.9%和70.7%(P=0.041)。两组5年OS分别为97.0%和95.1%;P=0.815)。单因素分析LMR、LYM%和Ⅳ期是儿童HL的EFS预后因素;多因素分析LMR为非独立预后因素,仅Ⅳ期为独立预后因素。结论本研究显示儿童HL患者初诊外周血LMR是影响EFS的预后因素之一,值得进一步研究。