Nonclinical safety profile of telbivudine, a novel potent antiviral agent for treatment of hepatitis B

Telbivudine is a novel nucleoside drug recently approved for the treatment of patients with chronic hepatitis B. Its nonclinical safety was evaluated in a comprehensive program of studies, including safety pharmacology, acute and chronic toxicity, reproductive and developmental toxicity, genotoxicity, and carcinogenicity. There were no test article-related effects observed in an in vitro hERG assay or in a core battery of safety pharmacology studies (central nervous system, respiratory, and cardiovascular safety pharmacology studies). Telbivudine was well tolerated in rats and in monkeys following single oral doses up to 2,000 mg/kg/day. Except for equivocal axonopathic findings in monkeys and occasional incidences of emesis, soft feces, and minor changes in body weight and food consumption, there was no target organ toxicity observed in mice, rats, or monkeys following oral administration for up to 3, 6, or 9 months, respectively, at doses up to 3,000 mg/kg/day. Axonopathy in the sciatic nerves and in the spinal cords of monkeys dosed at 1,000 mg/kg/day observed in a 9-month study was considered equivocal, as the role of telbivudine in the injury could not be determined. Slightly higher incidences of abortion and premature delivery observed in rabbits dosed at 1,000 mg/kg/day were considered secondary to maternal toxicity. There was no evidence of genotoxicity or carcinogenicity. These results suggest that telbivudine has a favorable safety profile and support its use in patients with chronic compensated hepatitis B viral infection.     

Pink1/Parkin-Mediated Mitophagy Regulated the Apoptosis of Dendritic Cells in Sepsis

Inflammation - Dendritic cells (DCs) are vital antigen-presenting cells (APCs) in the immune system, whose apoptosis is closely related to the development of sepsis. Mitophagy is one of the...     

面孔认知中性别信息对N170的影响

目的:了解面孔认知中性别信息对N170的影响。方法:于2005-03选择南方医科大学本科大学生40人作为受试者,均右利手,视力正常或矫正视力正常。无精神疾患以及精神病家族史,自愿参加实验。选取对所有受试者均为陌生的360张真人面孔(男女各半)照片用作刺激,随机顺序依次呈现,每张照片呈现1次。刺激持续时间800ms,间隔1200ms。实验任务为要求受试者对所呈现的面孔照片的性别作出按键反应(一半受试者对男性面孔按左键,女性面孔按右键,另一半相反)。采用本实验室开发的通用型19导事件相关电位系统进行脑电记录以及数据处理。记录电极按国际10～20标准导联系统安装;连接的双侧耳垂为参考;接地电极置于前额正中。滤波通频带为[0.1,30]Hz,数字化采样率1000Hz,头皮与电极之间的阻抗<5kΩ;记录分析时间为刺激前100ms至刺激后800ms。排除眼动和肌电等伪差。每名受试者同性别面孔刺激每60次为一个叠加单位(除去质量较差的脑电片段,实际叠加45～50次)。每名受试者采集6个波形片段数据(男女刺激面孔各3个),共取得34×6个波形片段数据。测量右颞后导联事件相关电位波形中的N170成分的波幅及潜伏期。对男、女两类面孔照片所诱发的N170波幅和潜伏期进行配对t检验。结果:排除脑电记录不满意者男女各3人,进入结果分析34人,(男17人,女17人)。①受试者34人右颞后部均诱发出较理想的N170成分,其总叠加波形潜伏期约为193ms。②男性面孔诱发的N170平均波幅(3.69±2.42)μV,平均潜伏期(191.84±18.98)ms;女性面孔诱发的N170平均波幅(3.66±2.36)μV,平均潜伏期(197.01±26.46)ms。③不同性别面孔刺激所诱发的N170的波幅差异无显著性意义;不同性别面孔刺激所诱发的N170的潜伏期差异有显著性意义(P<0.05)。结论:表征面孔整体加工的N170受面孔性别因素的影响。大脑对面孔进行结构编码时可能同时需要处理性别等信息。     

Increased TIM-3+PD-1+ NK cells are associated with the disease activity and severity of systemic lupus erythematosus

It is well established that natural killer (NK) cells are dysregulated in systemic lupus erythematosus (SLE) patients. However, the functions of NK cells and the mechanisms regulated by them in SLE remain incompletely understood. Patients with SLE were recruited from The First Affiliated Hospital of Nanchang University, and their clinical characteristics and treatments were recorded. The expression levels of T cell immunoglobulin mucin-3 (TIM-3) and programmed cell death protein 1 (PD-1) on NK cells were examined using flow cytometry. The correlations between the increase in TIM-3⁺PD-1⁺ NK cells in the SLE patients and clinical traits, including inflammatory markers, auto-antibodies, disease activity and severity of SLE, were examined. The TIM-3⁺NK cells, PD-1⁺NK cells and TIM-3⁺PD-1⁺ NK cells were significantly increased in the SLE patients. The increase in TIM-3⁺PD-1⁺ NK cells in the patients with SLE was associated with erythrocyte sedimentation rate, C-reactive protein, anti-double stranded DNA, anti-ribosomal P, SLE disease activity index and clinical features. The frequency of TIM-3⁺PD-1⁺NK cells in SLE patients with a cardiovascular disease (CVD) was significantly lower than that in SLE patients without a CVD. Moreover, the increased TIM-3⁺PD-1⁺ NK cells were significantly decreased in SLE patients following treatment. The present study suggested that the increased TIM-3⁺PD-1⁺ NK cells were associated with the disease activity and severity of SLE and may play a role in SLE pathogenesis.

     

小鼠皮肤超氧化物歧化酶活性与枸杞多糖的干预

目的:观察枸杞多糖对皮肤胶原代谢和自由基产生的影响,探讨其抗皮肤衰老的作用。方法:实验于2005-06/2006-05在广东医学院整形外科研究所完成。①实验材料:清洁级昆明小鼠60只,月龄2个月,体质量16～24g,雌雄各半。②实验分组:将小鼠随机分为正常对照组、衰老模型组和抗衰老模型组,每组20只。③实验干预:模型组每日用D-半乳糖溶液皮下注射制造衰老模型,用量和时间为80mg/(kg·d)7d,120mg/(kg·d)14d,140mg/(kg·d)14d,180mg/(kg·d)7d。正常对照组每日注射同体积的生理盐水。抗衰老模型组在注射D-半乳糖期间以枸杞多糖灌胃,剂量为20mg/(kg·d),正常对照组和衰老组则以同体积的生理盐水代之灌胃。④实验评估:42d后切取小鼠颈背部皮肤,测定超氧化物歧化酶活力、羟脯氨酸和丙二醛含量。结果:56只小鼠进入结果分析(4只死亡)。①小鼠皮肤超氧化物歧化酶活力:与正常对照组相比,衰老组和抗衰老组小鼠皮肤超氧化物歧化酶活力降低,差异有显著性意义(P<0.01);抗衰老组与衰老模型组比较,超氧化物歧化酶活力增加,差异有显著性意义(P<0.01)。②与正常对照组相比,衰老组和抗衰老组小鼠皮肤羟脯氨酸和丙二醛含量增加,差异有显著性意义(P<0.01);抗衰老组与衰老组比较,羟脯氨酸和丙二醛含量均降低,差异有显著性意义(P<0.01)。结论:枸杞多糖改善皮肤老化的作用与提高小鼠皮肤超氧化物歧化酶活力,降低羟脯氨酸、丙二醛含量,影响胶原代谢有关。     

对乳腺弹性成像5分评分法的进一步探讨

目的进一步探讨乳腺超声弹性成像（UE）5分法判断乳腺病灶良恶性的准确性。 方法对469例乳腺肿物患者共631个肿物进行超声弹性成像检查,对照术后病理结果回顾性分析乳腺肿物良恶性病灶在1～5评分分布的差异。 结果乳腺超声弹性成像评分为1、2分的主要是良性病灶,4、5分的主要是恶性病灶,在这4点上乳腺良恶性病灶的分布差异有统计学意义（P〈0.05）;评分为3分的乳腺良恶性病灶的分布差异没有统计学意义（P〉0.05）。 结论3分为乳腺癌良恶性的分界点,要结合临床、二维及彩色多普勒超声检查进行判断,必要时要进行术前病理活检来确定病灶的良恶性。     

60Coγ射线局部辐射后小鼠非辐射区域骨髓巨核细胞的变化

目的:临床局部辐射条件下会造成非辐射区域组织及细胞功能损害,最为突出的是对造血功能的影响。实验建立60Coγ射线左半身辐射动物模型,观察局部电离辐射对其非辐射区域骨髓巨核细胞的影响。方法:实验于2003-10/2005-03在解放军第三军医大学辐照中心和全军复合伤研究所完成。①实验动物:6～8周龄SPF级雄性昆明小鼠180只,随机数字表法分为正常对照组、全身辐射组、左半身辐射组、全身屏蔽辐射组,45只/组。②实验方法:全身辐射组小鼠固定于辐射架内;左半身辐射组小鼠麻醉后固定体位,用铅砖屏蔽右半身;全身屏蔽辐射组小鼠麻醉固定体位,用铅砖屏蔽全身。以60Coγ射线一次性辐射,剂量率68.46cGy/min。正常对照组不作任何干预。③实验评估:辐射后不同时相检测小鼠血清丙二醛含量及超氧化物歧化酶活性变化,计数外周血血小板,检测骨髓巨核祖细胞集落形成单位,观察骨髓组织病理改变及CD41a、CD61的表达。结果:全身辐射组第8天死亡2只,第9天死亡4只,其余各组无脱失。①外周血血小板计数:辐射后第2,7天,左半身辐射组外周血血小板数量显著低于正常对照组(P<0.01),但高于全身辐射组(P<0.01)。②血清丙二醛含量及超氧化物歧化酶活性变化:辐射后第2,9天,左半身辐射组血清丙二醛含量显著高于正常对照组(P<0.01),低于全身辐射组(P<0.01);血清超氧化物歧化酶活性显著低于正常对照组(P<0.01),高于全身辐射组(P<0.01)。③骨髓巨核祖细胞集落形成单位的变化:与正常对照组比较,辐射后6h左半身辐射组非辐射侧的巨核祖细胞集落形成单位显著降低(P<0.01),高于全身辐射组及左半身辐射组(P<0.01)。④骨髓组织病理改变:正常对照组有核细胞比例较高,分布均匀,并见多量散在分布的细胞龛;辐射2d后,左半身辐射组非辐射侧骨髓有核细胞较正常对照组减少,但好于全身辐射组、左半身辐射组。⑤骨髓CD41a及CD61表达的变化:辐射后2d与正常对照组比较,左半身辐射组非辐射侧骨髓CD41a及CD61阳性细胞数和相对荧光强度均显著降低(P<0.01),但高于全身辐射组、左半身辐射组(P<0.01)。结论:局部电离辐射作用后,可导致小鼠非辐射区域骨髓巨核细胞增殖能力降低,血小板减少,产生功能障碍。氧自由基激活可能参与了该损伤过程。     

胃复安、非那根联合用药与格拉斯琼在防治化疗引起呕吐的疗效观察

目的观察以胃复安、非那根联合用药防治顺铂化疗引起呕吐的疗效。方法随机分为两组，一组为观察组，接受胃复安、非那根联合止吐，一组为对照组，接受格拉斯琼止吐。结果联合用药取得与格拉斯琼相似的止吐效果。结论胃复安＋非那根药价低，疗效好，在非禁忌病人及经济困难病人可选用。     

阴道超声在腹腔镜治疗异位妊娠术前的应用价值

目的 探讨术前阴道超声检查在腹腔镜治疗异位妊娠手术中的应用价值。方法 对79例通过腹腔镜手术治疗的异位妊娠，进行回顾性分析，将术前阴道超声所见与术中所见进行对照，进一步明确腹腔镜手术治疗异位妊娠的适应证。结果 阴道超声检查与腹腔镜手术所见病变完全一致的73例（占92．4％），余6例与术中所见有所误差（占7．6％），阴道超声诊断的未破裂的异位妊娠全部适应腹腔镜手术，而诊断宫角、间质部妊娠破裂或流产型异位妊娠，盆腔积血较多且局限在某一部位者，盆腔粘连较重时，要慎重选择腹腔镜手术，并做好术中更改术式的准备。结论 为提高腹腔镜治疗异位妊娠手术的成功率，阴道超声是术前不可缺少的检查手段。