Characterization and phylogenetic analysis of a neurovirulent Zika virus isolated from Cambodia in 2019

The geographic range of Zika virus (ZIKV) has expanded from Asia to the Americas, leading to the 2015–2016 pandemic with enhanced neurovirulence. At present, ZIKV is continuously circulating in many Southeast Asian countries. Unfortunately, the persistent evolution of ZIKV in Southeast Asia and its influence on the biological characteristics of the virus remain incompletely understood. In this study, the in vitro and in vivo properties of a new ZIKV isolate obtained from Cambodia in 2019 (CAM/2019) were characterized and compared with those of the Cambodian strain (CAM/2010). Compared with CAM/2010, the CAM/2019 virus showed similar plaque morphology and growth curves in cell cultures and induced comparable viremia and organ viral loads profiles in both BALB/c and A129 (IFNAR1^−/−) mice upon intraperitoneal (i.p.) inoculation. Remarkably, the CAM/2019 virus exhibited enhanced neurovirulence in neonatal mice compared with CAM/2010, with a 74-fold reduction in the 50% lethal dose (LD₅₀). Consistently, CAM/2019 produced higher viral loads in the brains of BALB/c neonatal mice than CAM/2010 did. Sequence alignment showed that the CAM/2019 virus has acquired 12 amino acid substitutions, several of which were found to be associated with neurovirulence. In particular, the CAM/2019 virus shared an A1204T substitution in NS2A with the Thai isolate SI-BKK02 that was isolated from a microcephaly case. Taken together, our results indicate that a ZIKV strain isolated with specific mutations has emerged in Cambodia, highlighting the need for extensive molecular and disease surveillance in Cambodia and other Asian countries.     

血清HA、PCⅢ对慢性肝炎、肝硬化的诊断价值

目的 探讨血清ＨＡ、ＰＣⅢ对慢性肝炎,肝炎肝硬化的诊断价值,ＨＡ与ＰＣⅢ意相关关系以及它们的变化对预后的影响。方法 采用ＲＩＡ法同时检测慢性肝炎、肝炎肝硬化患者血清ＨＡ、ＰＣⅢ含量,比较ＨＡ,ＰＣⅢ间关系,肝炎肝硬化组中存活病例与死亡病例的ＨＡ、ＰＣⅢ变化情况。     

Rhenium-188-Labeled DTPA: a new radiopharmaceutical for intravascular radiation therapy

Balloon angioplasty is a standard treatment for artherosclerotic coronary artery disease. However, its clinical value is reduced by a high restenosis rate. A new concept in preventing restenosis is the use of a liquid-filled balloon containing a beta-emitting radioisotope. In this study, we performed biodistribution studies of Re-188 perrhenate and Re-188 diethylenetriaminopentaacetate (DTPA) to assess the resulting organ dose values in the event of balloon rupture if these agents are used for the clinical inhibition of restenosis after percutaneous transluminal coronary angioplasty (PTCA). After injecting Re-188 preparations intravenously, rats were killed at 10 min, 30 min, 60 min, 2 h, and 6 h ( n =5 per group). Tissue concentrations were calculated and expressed as percent injected dose per gram or per milliliter (%ID/g or %ID/mL). In addition, urine excretion and thyroid gland uptake were evaluated in rats ( n=5 per group) with a gamma camera after administration of 37 MBq (1 mCi) of each agent. Our data showed that both agents were excreted primarily via urine. However, the excretion of Re-188 DTPA was much faster than that of Re-188 perrhenate via the urinary system. The biodistribution data revealed that radioactivity levels in the stomach and the thyroid gland were high in the perrhenate group but low in the Re-188 DTPA group. The concentration levels in other tissues including lung, liver, testis, muscle, and blood were low throughout this study for both agents. The thyroid radiation value in the Re-188 perrhenate group was 0.163 mGy/MBq, which was much higher than that of the Re-188 DTPA group (0.0167 mGy/MBq). The stomach radiation value was as high as 0.127 mGy/MBq for Re-188 perrhenate, compared with 0.013 mGy/MBq for Re-188 DTPA. In conclusion, in the event of balloon rupture, the release of Re-188 DTPA results in lower radiation doses than Re-188 perrhenate, especially to the thyroid gland and the stomach. Our data suggest that Re-188 DTPA is a useful radiopharmaceutical for endovascular irradiation.     

内眼手术前,后结膜囊细菌学研究

目的:探索眼科内眼手术前后结膜囊细菌学变化特点及临床眼科用药效果。方法:133眼需要行内眼手术的连续病例包括白内障手术68眼、青光眼手术39眼、视网膜脱离手术20眼、玻璃体切割术6眼。用133眼内眼手术病人手术前后的结膜刮片及68眼白内障手术术毕的前房冲洗液作细菌培养,并作药敏试验。结果:133眼内眼手术患者入院时结膜刮片作细菌培养有61眼(45.85％)培养出细菌,其中金黄色葡萄球菌23眼、表皮葡萄球菌25眼、G~ 杆菌13眼;手术消毒前结膜囊刮片有8眼(6％)仍培养出细菌,其中金黄色葡萄球菌3眼,表皮葡萄球菌5眼;68眼白内障手术患者前房冲洗液中仅1眼(1.5％)培养出细菌,为表皮葡萄球菌;术毕时结膜刮片4眼(3％)培养出细菌,所培养出来的细菌均对妥布霉素、庆大霉素、先锋Ⅵ、万古霉素和利福平敏感,而对四环素、氯霉素、红霉素、氧氟沙星耐药。结论:肉眼手术前应用有效抗菌素至为重要,可预防眼内炎的发生,但不可轻视手术无菌操作。眼科学报1999;15:267-269。     

HIV-1 infected mononuclear phagocyte secretory products affect neuronal physiology leading to cellular demise: relevance for HIV-1-associated dementia

Viral and cellular products from HIV-1-infected and/or immune competent mononuclear phagocytes (MP) (brain macrophages and microglia) affect neuronal function during HIV-1-associated dementia (HAD). Neurotoxic MP factors include, but are not limited to, pro-inflammatory cytokines, chemokines, platelet activating factor, arachidonic acid and its metabolites, nitric oxide, progeny virions and viral structural and regulatory proteins. The mechanisms for immune-mediated neural injury in HAD, only now, are being unraveled. In this regard, we reviewed the current knowledge of how postmitotic neurons, which can neither divide nor be replaced, are damaged by MP secretory activities. Linking neuronal function with brain MP activation was made possible by placing viral and/or immune products onto neurons and measuring cell signaling events or through ex vivo electrophysiological tests on MP-treated brain slices. Such linkages are shown, in this report, by select demonstrations of MP factors which cause neuronal dysfunction in HAD.     

RP-HPLC测定犬血浆中卡托普利

目的　采用反相高效液相色谱法测定犬血浆中卡托普利浓度。方法　以对溴苯乙酰基溴为衍生剂 ,血浆样品经衍生反应后 ,用乙酸乙酯 -苯 (1∶1)提取 ,以ODSC18为固定相 ,乙腈∶水∶冰醋酸 (4 5∶5 5∶0 2 )为流动相 ,UV2 5 8nm紫外检测。结果　在 2 5～ 6 0 0 μg·L-1浓度范围线性良好 ,最小检测浓度为 12 5 μg·L-1。其日内差及日间差RSD分别小于 4 95 %和 2 88% ,相对回收率大于 94 8%。结论　方法简便灵敏 ,为卡托普利样品分析及临床药物监测提供了检测方法。     

Salicylate enhances necrosis and apoptosis mediated by the mitochondrial permeability transition.

Onset of the mitochondrial permeability transition (MPT) causes both necrotic and apoptotic cell death in cultured hepatocytes. Salicylate lowers the threshold for onset of the MPT. In this study, our aim was to determine whether nontoxic concentrations of salicylate potentiate MPT-mediated cell killing. In necrotic killing models to rat hepatocytes, salicylate (1 mM) enhanced calcium ionophore (Br-A23187)- and tert-butylhydroperoxide (t-BuOOH)-induced cell death, which was blocked or delayed by cyclosporin A (CsA, 2 microM), a specific inhibitor of the MPT. In hepatocyte apoptosis induced by tumor necrosis factor-alpha (TNF-alpha), salicylate accelerated cell killing after low-dose TNF-alpha (1 ng/ml), which by itself induced little apoptosis. Salicylate enhancement of apoptosis was associated with onset of the MPT and accelerated caspase 3 activation. Salicylate also augmented killing of MCF-7 human breast tumor cells by etoposide and PLC/PRF/5 human hepatoma cells by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). In conclusion, salicylate potentiates both necrotic and apoptotic cell killing by promoting onset of the MPT. Enhancement by salicylate of MPT-dependent apoptosis may play a role in protection by aspirin and other nonsteroidal anti-inflammatory drugs against colon, lung, and breast cancer.     

Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor, in combination with gemcitabine for advanced pancreatic cancer: a multicenter phase II Trial.

PURPOSE: To determine the response rate, time to disease progression, survival duration and rate, and toxicity with the combination of cetuximab and gemcitabine in patients with epidermal growth factor receptor (EGFR)-expressing advanced pancreatic cancer. PATIENTS AND METHODS: Patients with measurable locally advanced or metastatic pancreatic cancer who had never received chemotherapy for their advanced disease and had immunohistochemical evidence of EGFR expression were eligible for the multicenter phase II trial. Patients were treated with cetuximab at an initial dose of 400 mg/m(2), followed by 250 mg/m(2) weekly for 7 weeks. Gemcitabine was administered at 1,000 mg/m(2) for 7 weeks, followed by 1 week of rest. In subsequent cycles, cetuximab was administered weekly, and gemcitabine was administered weekly for 3 weeks every 4 weeks. RESULTS: Sixty-one patients were screened for EGFR expression, 58 patients (95%) had at least 1+ staining, and 41 were enrolled onto the trial. Five patients (12.2%) achieved a partial response, and 26 (63.4%) had stable disease. The median time to disease progression was 3.8 months, and the median overall survival duration was 7.1 months. One-year progression-free survival and overall survival rates were 12% and 31.7%, respectively. The most frequently reported grade 3 or 4 adverse events were neutropenia (39.0%), asthenia (22.0%), abdominal pain (22.0%), and thrombocytopenia (17.1%). CONCLUSION: Cetuximab in combination with gemcitabine showed promising activity against advanced pancreatic cancer. Further clinical investigation is warranted.     

Treatment of 78 cases of shoulder periarthritis by warming-needle method

Jiansanzhen, Tianzong (SI 11), Jugu (LI 16), Jianzhen (SI 9), Binao (LI 14) and Quchi (LI 11) were given warming-needle moxibustion to treat shoulder periarthritis in 78 cases, and the result showed total effective rate was 97.4%. Author: LI Jian-wu (1955-), male, junior consultant doctor Translator: WU Xue-fei