尿毒清颗粒配合结肠透析治疗慢性肾功能衰竭疗效观察

目的 观察尿毒清颗粒配合结肠透析治疗对慢性肾功能衰竭（chronic renal failure,CRF）早中期患者的临床疗效.方法 收集我院76例慢性肾功能衰竭早中期患者,随机分为对照组和治疗组各38例.对照组行常规结肠透析,治疗组在常规结肠透析治疗基础上加用尿毒清颗粒保留灌肠,两组患者均行3疗程治疗.两组患者在第一次治疗前及最后一次治疗后检测血尿素氮（BUN）、血肌酐（Scr）、血尿酸（UA）.结果 治疗组和对照组BUN、Scr、UA较治疗前明显下降,治疗组的下降幅度较对照组明显,两组间差异有统计学意义（P＜ 0.05）.结论 尿毒清颗粒配合结肠透析治疗慢性肾功能衰竭患者临床疗效优于常规结肠透析,尿毒清颗粒保留灌肠在慢性肾功能衰竭结肠透析治疗中具有优势.     

养血清脑颗粒联合纳洛酮治疗眩晕症的效果观察

目的探讨养血清脑颗粒联合纳洛酮治疗眩晕症的的临床效果及安全性。方法 2009年10月～2013年1月入选眩晕症患者100例,按治疗方法分为治疗组和对照组。治疗组予以口服养血清脑颗粒,同时联用纳洛酮静脉滴注;对照组采用维生素C＋维生素B6＋三磷酸腺苷（ATP）＋地塞米松5 mg加入5%葡萄糖250 ml中静脉滴注。两组的治疗周期均为5 d。结果治疗组中显效51例,有效6例,无效5例,总有效率为95%,对照组中显效10例,有效10例,无效20例,总有效率为50%,两组的总有效率比较,差异有统计学意义（P=0.0004）。结论养血清脑颗粒联合纳洛酮治疗眩晕症具有很好的临床应用意义。     

醒脾养儿颗粒辅助治疗小儿肺炎继发性腹泻的效果观察

目的：醒脾养儿颗粒辅助治疗小儿肺炎继发性腹泻的临床效果及安全性观察。方法选取2010年3月~2014年9月本院收治的160例肺炎继发性腹泻患儿,将其按照随机数字表法研究组和对照组,各80例。两组患儿均给予肺炎继发性腹泻的常规治疗措施,同时对照组给予口服思密达,研究组加服醒脾养儿颗粒。治疗1个疗程后,对两组患儿治疗效果、患儿症状体征改善情况及血清胃泌素(GAS)、胃动素(MOT)、生长抑素(SS)水平进行比较。结果经治疗1个疗程后,研究组的治疗总有效率达到91.25%,显著高于对照组的80.00%,差异有统计学意义(P<0.05);在治疗期间,研究组腹泻、发热、呕吐持续时间分别为(36.3±9.6)、(40.6±6.9)、(35.5±7.4)h,对照组分别为(48.0±11.2)、(46.1±8.2)、(42.5±11.7)h,两组差异有统计学意义(P<0.05);与同组治疗前比较,两组患儿经治疗后的血清GAS和MOT水平明显下降,SS水平明显升高(P<0.05);与对照组治疗后比较,研究组的GAS和MOT水平降低幅度及SS水平升高幅度更为显著,差异均有统计学意义(P<0.05),两组患儿均未见明显药物不良反应。结论醒脾养儿颗粒辅助治疗小儿肺炎继发性腹泻的效果显著,可迅速缓解患儿腹泻症状,缩短肺炎治疗时间,同时醒脾养儿颗粒对患儿血清GAS、MOT、SS水平具有明显的调节作用,值得临床推广应用。     

Addressing Antiretroviral Drug Resistance with Host-Targeting Drugs—First Steps towards Developing a Host-Targeting HIV-1 Assembly Inhibitor

The concerning increase in HIV-1 resistance argues for prioritizing the development of host-targeting antiviral drugs because such drugs can offer high genetic barriers to the selection of drug-resistant viral variants. Targeting host proteins could also yield drugs that act on viral life cycle events that have proven elusive to inhibition, such as intracellular events of HIV-1 immature capsid assembly. Here, we review small molecule inhibitors identified primarily through HIV-1 self-assembly screens and describe how all act either narrowly post-entry or broadly on early and late events of the HIV-1 life cycle. We propose that a different screening approach could identify compounds that specifically inhibit HIV-1 Gag assembly, as was observed when a potent rabies virus inhibitor was identified using a host-catalyzed rabies assembly screen. As an example of this possibility, we discuss an antiretroviral small molecule recently identified using a screen that recapitulates the host-catalyzed HIV-1 capsid assembly pathway. This chemotype potently blocks HIV-1 replication in T cells by specifically inhibiting immature HIV-1 capsid assembly but fails to select for resistant viral variants over 37 passages, suggesting a host protein target. Development of such small molecules could yield novel host-targeting antiretroviral drugs and provide insight into chronic diseases resulting from dysregulation of host machinery targeted by these drugs.     

Melatonin protects neurons from singlet oxygen-induced apoptosis

Abstract: Singlet oxygen (O₂[¹Δg]) is a very reactive molecule that can be produced by living cells and may contribute to cytotoxicity. The pineal hormone melatonin has been reported to possess potent antioxidant activity, and to be capable of scavenging O₂(¹Δg). We investigated whether melatonin might reduce the neurotoxic action of O₂(^lΔg). The cytotoxic effect of singlet oxygen was studied in primary cultures of cerebellar granule neurons pretreated with a photosensitive dye, rose bengal, and exposed to light—a procedure that generates O₂(¹Δg). We found that this procedure triggers neuronal death, which is preceded by mitochondrial impairment (assayed by the rate of the reduction of MTT, 3-[4,5-di-methylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide, into formazan), and by DNA fragmentation—a marker of apoptosis. DNA fragmentation was determined in situ by terminal deoxynucleotidyl transferase assay; cell death was assayed with 0.4% trypan blue solution—viable cells with an intact membrane are not permeable to trypan blue; dead cells are, and thus, they are stained blue. Neuroprotection was obtained with the pineal hormone melatonin. In a cell-free system, melatonin also protected the enzyme creatine kinase (EC 2.7.3.2) from the rose bengal-induced injury. The results suggest that melatonin might counteract the cytotoxic action of singlet oxygen. Further studies are needed to clarify the exact role singlet oxygen and melatonin might play in neurodegenerative diseases.     

Characterization of rat somatotroph and mammotroph secretory granules. Presence of sulfated molecules

The contents of a purified somatotroph and mammotroph secretory granule fraction isolated from rat anterior pituitaries were solubilized in 4 M urea and analyzed by PAGE. In gels electrophoresed under a variety of conditions and stained with Coomassie Blue only two major bands, identified as GH and PRL, were present. In gels stained with Stains-All (which stains anionic substances), several additional bands were detected. When quarter pituitaries were labeled with a [3H]amino acid mixture, GH and PRL accounted for greater than 95% of the radioactivity incorporated into the granules. After labeling with [35S]sulfate, two classes of radiolabeled sulfated components were detected in the granules: a class of trypsin-sensitive macromolecular components which were coincident with two of the bands seen after Stains-All, and a class of low molecular weight components. In order to examine the distribution of the two classes of sulfated components within somatotroph and mammotroph granules, granules were suspended in 0.4% (w/v) Lubrol PX at pH 4.0, a treatment which has been shown to selectively solubilize somatotroph granule contents leaving mammotroph granule cores intact. This treatment was found to solubilize greater than 95% of the GH and greater than 99% of the radiolabeled, low molecular weight sulfated components; in contrast, there was virtually no solubilization of either PRL or macromolecular sulfated components. The findings indicate (a) that [35S]sulfate is incorporated into both somatotroph and mammotroph granules, and (b) that the low molecular weight sulfated components are associated with somatotroph granules whereas the macromolecular sulfated components are associated with mammotroph granules.     

养血清脑颗粒联合氟哌噻吨美利曲辛治疗紧张性头痛临床疗效观察

目的：研究养血清脑颗粒联合氟哌噻吨美利曲辛治疗紧张性头痛的临床疗效。方法：将2011年12月-2014年2月本院门诊收治的68例紧张性头痛患者给予养血清脑颗粒联合氟哌噻吨美利曲辛治疗,观察治疗前后的头痛程度、负面情绪及生活质量。结果：治疗后患者头痛程度及负面情绪评分明显低于治疗前,生活质量明显高于治疗前;患者的疼痛数字量表（NRS）评分为（1.4±0.2）分、汉密尔顿焦虑量表（HAMA）评分为（13.6±1.5）分、汉密尔顿抑郁量表（HAMD）评分为（13.8±2.6）分,均明显低于治疗前;躯体功能（72.8±9.6）分、心理功能（59.5±5.6）分、社会功能（57.7±2.87）分、总体生活质量（81.3±8.8）分,均明显高于未治疗前（P〈0.05）。结论：养血清脑颗粒联合氟哌噻吨美利曲辛有助于缓解头痛和负面情绪,提高患者的疼痛耐受性,对治疗紧张性头痛具有重要意义。     

参地颗粒对慢性肾炎脾肾亏虚证患者血清 VEGF、尿 EGF 的干预作用

目的：观察慢性肾小球肾炎（ CGN）脾肾亏虚证患者血清血管内皮生长因子（ VEGF）和尿表皮生长因子（EGF）的变化及参地颗粒的干预作用。方法：64例 CGN 脾肾亏虚证患者随机分为对照组和治疗组各32例,实际完成61例（对照组31例,治疗组30例）,并设正常组20例。治疗组口服参地颗粒,对照组口服氯沙坦钾片,疗程均为8周,观察治疗前后临床疗效、24 h 尿蛋白定量、尿红细胞计数、血清 VEGF 和尿 EGF 水平变化,并与正常组比较。结果：治疗组临床疾病总有效率和中医证候疗效总有效率均为86．67%,优于对照组的61．30%（P 〈0．05）;治疗组治疗后24 h 尿蛋白定量、尿红细胞计数均较治疗前降低（P 〈0．05）,而对照组治疗后24 h 尿蛋白定量较治疗前降低（P 〈0．05）,但尿红细胞计数降低不明显（P 〉0．05）;两组患者治疗前血清 VEGF 和尿 EGF 水平明显高于正常组（P 〈0．01）,治疗后两组血清 VEGF 和尿 EGF 水平均下降（P 〈0．05）,且治疗组优于对照组（P 〈0．05）。结论：CGN 脾肾亏虚证患者血清 VEGF、尿 EGF 水平上升,参地颗粒可显著降低患者血清 VEGF、尿 EGF 水平,降低中医证候积分,改善临床症状,其机制之一可能与其降低患者血清 VEGF、尿 EGF 水平有关。     

温阳解毒化瘀颗粒对肠源性内毒素血症大鼠肠黏膜上皮紧密连接的影响

目的：研究温阳解毒化瘀颗粒对肠源性内毒素血症（ IETM ）模型大鼠结肠黏膜上皮紧密连接的影响,探索其抗肝衰竭的作用机制。方法：将大鼠随机分为正常组、模型组、温阳解毒化瘀颗粒（实验组）和对照组4组,采用D-半乳糖胺（D-gal）腹腔注射致肝衰竭ITEM大鼠模型。正常组在腹腔注射生理盐水24h后处死,模型组、实验组、对照组分别于造模后24h、48h、72h各取6只、7只、7只大鼠处死,检测各组肝功能、内毒素、结肠黏膜上皮咬合蛋白（occludin）及肌球蛋白轻链激酶（MLCK）。结果：模型组血清ALT/AST、内毒素、 MLCK表达水平均高于正常组, occludin表达低于模型组（ P＜0.01）;实验组血清ALT/AST、内毒素、 MLCK表达水平均低于模型组, occlu-din表达高于模型组（ P＜0.05）。结论：增强结肠粘膜上皮紧密连接功能,降低内毒素的吸收是温阳解毒化瘀颗粒抗肝衰竭的作用机制之一。     

Genetic variants associated with Hermansky-Pudlak syndrome

Abstract

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by defective biogenesis of lysosome-related organelles. Clinical manifestations include a bleeding diathesis due to a platelet delta storage pool deficiency, oculocutaneous albinism, inflammatory bowel disease, neutropenia, and pulmonary fibrosis. Ten genes associated with HPS are identified to date, and each gene encodes a protein subunit of either Biogenesis of Lysosome-related Organelles Complex (BLOC)-1, BLOC-2, BLOC-3, or the Adaptor Protein-3 complex. Several genetic variants and phenotypic heterogeneities are reported in individuals with HPS, who generally exhibit easy bruisability and increased bleeding. Desmopressin, pro-coagulants, or platelet transfusion may be used as prophylaxis or treatment for excessive bleeding in patients with HPS. However, response to desmopressin can be variable. Platelets are effective in preventing or treating bleeding in individuals with HPS, but platelets should be transfused judiciously to limit alloimmunization in patients with HPS who are at risk of developing pulmonary fibrosis and may be potential candidates for lung transplantation. The discovery of new genes associated with HPS in people with excessive bleeding and hypopigmentation of unknown etiology may be facilitated by the use of next-generation sequencing or panel-based genetic testing.