论虚寒证基因芯片及生物信息的高起点切入研究——分子中医研究系列报道(1)

从辨证论治的 3点不足 ,前瞻现代数理思维的重要性 ,引进前沿生物科技的必要性 ;从虚寒证的研究基础和寒的本义论述了虚寒证现代研究的优势 ;对于虚寒证等中医复杂证候的研究 ,必须多学科的交叉 ,尤其是目前可利用的利器 :基因芯片、生物信息等 ,可望从虚寒证的基因组研究切入 ,突破“证”的瓶颈     

Contradictory effects of chlorpromazine on endothelial cells in a rat model of endotoxic shock in association with its actions on serum TNF-alpha levels and antioxidant enzyme activities.

We examined the effects of the phenothiazine derivative, chlorpromazine on thoracic aortic endothelial cell histology (14 h after LPS challenge) in a model of endotoxic shock in rats. Since excessive formation of tumor necrosis factor-alpha (TNF-alpha) and oxygen-derived free radicals contribute to endothelial injury in endotoxemia, we also evaluated the effect of the drug on the activities of antioxidant enzymes superoxide dismutase (SOD) and catalase in liver tissue in this model and tried to find out whether this possible effect was associated with a change in serum TNF-alpha levels (measured 90 min after chlorpromazine administration). Endotoxemia was induced by a single i.p. injection of lipopolysaccharide (LPS) (5 mg kg(-1) in 1.5 ml of saline; LPS from Escherichia coli serotype 055:B5, L-2880, Sigma Chemical Company). Electron microscopic evaluation of the aortas revealed that chlorpromazine (administered 30 min prior to LPS challenge), in smaller doses (3 mg kg(-1)) ameliorated the endothelial cell injury caused by LPS, whereas it caused deterioration of endothelial cell morphology in higher doses (10 and 25 mg kg(-1)). Chlorpromazine administration caused a significant reduction in serum TNF-alpha levels, which was correlated well with an increase in SOD activity in all drug doses (3, 10 and 25 mg kg(-1)). Catalase activity was increased only in the 25 mg kg(-1) chlorpromazine group.     

Effects of spinally and supraspinally injected 3-isobutyl-1-methylxanthine, cholera toxin, and pertussis toxin on immobilization stress-induced antinociception in the mouse.

The effects of intracerebroventricular (i.c.v.) and intrathecal (i.t.) 3-isobutyl-1-methylxanthine (IBMX), cholera toxin (CTX) and pertussis toxin (PTX) administration on immobilization-induced antinociception were studied in ICR mice. Antinociception was assessed by the tail-flick assay. Immobilization of the mouse increased inhibition of the tail-flick response for at least 1 h. The pretreatment with i.t. IBMX (0.01-1 ng), but not i.c.v. IBMX, significantly attenuated immobilization-induced inhibition of the tail-flick response. The pretreatments with i.c.v. PTX (0.05-0.5 microg) as well as i.t. CTX, but neither i.c.v. CTX (0.05-0.5 microg) nor i.t. PTX, potentiated the inhibition of the tail-flick response induced by immobilization stress. Our results suggest that spinally located phosphodiesterase appears to be involved in the production of immobilization stress-induced antinociception. In addition, inactivation of supraspinally located PTX-sensitive G-proteins and spinally located CTX-sensitive G-proteins may modulate immobilization stress-induced antinociception.     

Prognostic significance of c-kit mutation in localized gastrointestinal stromal tumors.

PURPOSE: Constitutive mutational activation of c-kit has been found to be associated with the pathogenesis of gastrointestinal stromal tumors (GISTs). The prognostic significance of c-kit mutations, however, is still controversial. EXPERIMENTAL DESIGN: We examined 86 patients curatively resected for localized GIST. Genomic DNA was extracted from paraffin-embedded tumor tissues. Exons 9, 11, 13, and 17 of the c-kit gene were amplified by PCR and sequenced. RESULTS: Mutations in exon 11 were detected in 61 tumors, and mutations in exon 9 were observed in three tumors, whereas no mutations were detected in exons 13 or 17. The overall c-kit mutation frequency was 74%. Amino acid alterations in the 61 tumors with exon 11 mutations were deletion in 33 tumors, substitution in 20, both deletion and substitution in 4, insertion in 1, and duplication in 3. Histologically, tumors with c-kit mutations showed higher mitotic counts and higher cellularity. The 5-year relapse-free survival (RFS) in patients having GISTs with c-kit mutations was 21%, compared with 60% in those without c-kit mutations. Significantly higher RFS rates were observed in patients with tumors having mitotic counts < 5 mitoses/50 high power field, spindle-cell histology, tumor size < 5 cm, or gastric GISTs. Multivariate analyses indicated association of poorer RFS with a higher mitotic count > or = 5 of 50 high power fields; odds ratio (OR) = 3.0], presence of c-kit mutations (OR = 5.6), and a larger tumor size (> or = 5 cm; OR = 4.2). CONCLUSIONS: The presence of c-kit mutation, along with high mitotic count and larger tumor size, was an independent factor for poor prognosis in patients with localized GISTs.     

Experimental validation tests of fast Fourier transform convolution and multigrid superposition algorithms for dose calculation in low-density media.

BACKGROUND AND PURPOSE: Modern conformal radiotherapy treatments require accurate dose calculation in any relevant clinical situation. One of these situations is the treatment of lung tumors, where irradiation has to be planned under challenging conditions for dose calculation. In this study we assess the errors in dose values predicted by fast Fourier transform convolution (FFTC) and multigrid superposition (MGS) algorithms implemented in a commercial treatment planning system (TPS). MATERIALS AND METHODS: FFTC and MGS algorithms were used in a FOCUS 3.0.0 (Computerized Medical Systems, USA) to calculate doses in treatment plans using photon beams of 6 and 25 MV nominal energy from a Saturne 43 linac (GE Medical Systems, USA). A 10x10-cm beam irradiating a mediastinum-lung and a thoracic wall-lung-thoracic wall modeled geometry was assessed. The calculated data were compared with measurements performed with radiographic films and ionization chamber. RESULTS: FFTC algorithm leads to an average deviation from ionometric dose measurements of over 10%. Discrepancies between measured and calculated beam fringe values (distance between 50 and 90% isodose lines) of up to 8 mm were observed. For MGS algorithm, all the points assessed in both geometries fulfilled the 3%-3 mm accuracy criteria and the average deviation of absolute dose was about 1%. A maximum of 3 mm deviation in the beam fringe for any depth was found and was within 2 mm beyond the buildup region. Deviations between ionometric and film measurements were within 3%. CONCLUSIONS: MGS algorithm assesses with reasonable accuracy dose distributions and absolute dose in inhomogeneous regions like the lung region. Therefore, and respecting the inhomogeneity dose calculation, the system could be used in routine clinical practice and in dose-escalation programs. This is not true in the case of FFTC algorithm which leads to errors greater than 10% in the absolute dose calculation and underestimates the beam fringe by up to 8 mm.     

羊红膻根的化学成分研究

从羊红膻(Pimpinella thellungiana Wolff.)根中分得四个化合物,经理化常数测定和光谱数据解析证明为棕榈酸(Ⅰ)、4-丙烯基苯酚(Ⅱ)、松酯酚(Ⅲ)和新化合物2-甲基-2-羟基-5-甲氧基苯并[d]氢化呋喃-3-酮(Ⅳ)。     

Salbutamol or mist in acute bronchiolitis

Abstract Background : The role of bronchodilators in the treatment of bronchiolitis remains controversial.
Methods : A double-blind, placebo controlled trial was performed to evaluate the clinical response to nebulized salbutamol. One hundred and fifty-six infants aged between 7 weeks and 24 months who had had an episode of wheezing and other signs and symptoms of bronchiolitis were randomized to three groups as follows: (i) nebulized salbutamol was administered to 52 patients in group I at a dose of 0.15 mg/kg in 2 mL saline; (ii) saline was nebulized to 52 patients in group II and (iii) in group III 52 patients received mist in a tent. All three groups were administered oxygen during the procedures. Treatment was repeated with the same agent after 30 min if the respiratory score was 5 or more. Respiratory rate, heart rate, oxygen saturation and presence of cyanosis, wheezing, retractions were recorded before and after each treatment.
Results : The decrease in the respiratory score was 5.2 ± 1.8, 0.82 ± 2.4 and 1.7 ± 1.3 in group I, II and III, respectively. The decrease in group I was significantly higher than in the other groups. Heart rate was similar between groups. Oxygen saturation decreased in group I without reaching statistical significance.
Conclusions: Salbutamol was shown to be effective and safe in the treatment of acute bronchiolitis.     

头孢克肟片和胶囊在健康人体的生物等效性

目的 评价头孢克肟片剂、胶囊剂与参比制剂在健康人体内的药代动力 学及其生物等效性。方法用三交叉全排列组合设计,18名健康男性受试者 交叉单剂量口服试验药头孢克肟片、胶囊和对照药头孢克肟胶囊剂,用高效液 相色谱法测定其的血药浓度。结果受试制剂头孢克肟片、胶囊与对照药头孢 克肟胶囊的Cmax分别为:(1．64±0．45),(1．58±0．37)和(1．67±O．46)μg· mL-1;tmax分别为:(3．78±0．38),(3．75±0．34)和(3．86±0．28)h;AUC0-24分 别为:(13．58±3．78),(13．49±3．63)和(13．36±4．16)mg·h·L-1;AUC0-∞ 分别为:(14．49±3．94),(14．32±3．87)和(14．05±4．31)mg·h·L-1。经统 计学分析,3组间均无显著性差异(P>0．05)。结论3种制剂具有生物等效 性。     

高能聚焦超声治疗子宫肌瘤300例疗效观察

目的 观察高能聚焦超声肿瘤治疗机对子宫肌瘤的治疗效果。方法 采用FEP—BY01型高能聚焦超声肿瘤治疗机对300例子宫肌瘤患者进行治疗；治疗3个月后，通过B超检验和患者临床症状对比对治疗效果进行评定。结果 子宫肌瘤体积缩小30％以上且B超回声明显增强者197例（65．67％）；瘤体缩小30％以下和（或）B超回声明显增强者94例（31．33％）；绝大多数患者临床症状改善。结论 高能聚焦超声对子宫肌瘤具有良好治疗效果。