用神经网络法预测药物在体透过人皮肤的渗透性

目的：预测药物在体透过人皮肤的渗透性。方法：以正辛醇／水分配系数(logP)、分子体积(V)、氢键酸度(∑β2^H)和氢键碱度(∑β2^H)等理化参数作为输入层神经元，以药物在一定时间内在体透过人皮肤的透过比的对数值(R，透过量／未透过量)作为输出层神经元，建立起合适的BP(Back—propagation)神经网络。结果：17个药物在一定时间内在体透过人皮肤的透过比的神经网络计算值和实测值均相当符合。结论：用BP神经网络法可以较好地预测药物在体透过人皮肤的渗透性。     

从极性原子净电荷预测药物在人体小肠中的吸收

目的：从极性原子净电荷预测药物在人体小肠中的吸收百分数和透过Caco-2单细胞层的渗透系数。方法：用分子力学MM＋法得到药物分子的优化几何构型，用Monte Carlo法计算分子体积，用半经验自洽场分子轨道CNDO／2法计算原子净电荷，相关分析采用逐步多元回归分析法。结果：药物分子在人体小肠中的吸收百分数和透过Caco-2单细胞层的渗透系数，均与氢键给体的原子净电荷之和（∑QH）与氢键受体的原子净电荷之和（∑QN.O）具有良好的相关性。氢键给体的正电荷和氢键受体的负电荷越多，药物分子在人体小肠中的吸收百分数和透过Caco-2单细胞层的渗透系数就越小。结论：药物在人体小肠中的吸收与其形成氢键能力密切相关。形成氢键能力弱的药物分子在人体小肠中的吸收较大。从极性原子净电荷参数预测药物在人体小肠中的吸收，具有方便快捷的优点，可用于候选口服药物的高通量筛选。     

发酵罐的放大——通气条件下搅拌转速的计算

在发酵罐放大过程中,通常希望生产罐的K_Lα值能与中试罐的K_Lα值相等。由于K_Lα=f(P_g/V,v_s)或K_Lα=f′(P_g/V,v_s,n)而P_g=f″(P,v_s,n),这对通过计算求出生产罐的搅拌转速n_2带来一定的不便。本文从Michel及Miller关联式出发得出P_g/V∝n~3.15d~2.35/v_(?)~0.252的比例关系,即可方便地求出n_2值。若采用K_Lα∝D/d~2.(d~2nρ/μ)~α·(dn~2/g)~β·(μv_s/σ)~γ.(nd/v_s)~δ…∝d~(2α β δ-2)n~(α 2β δ)v_s~(γ-δ)由无因次数群组成的方程式为基础进行放大计算时,则更方便。Yagi等提出的计算K_Lα值的准数方程式可以用作发酵罐放大的基础。此时,n_2=n_1(v_(s1)/v_(s2))~0.127(d_1/d_2)~0.686,P_2=P_1(v_(s1)/v_(s2))~0.381(d_2/d_1)~2.94,P_(g2)=P_(g1)(v_(s1)/v_(s2))~0.652(d_2/d_1)~3.19。     

抗TB化疗结局的Logistic回归解释和预测模型

目的：建立解释和预测抗TB化疗结局的Logistic回归模型。方法：采用病例对照研究方法及成组资料的非条件Logistic回归分析模型P=1/{1 exp[-(a ∑bjXj]}，对277例涂阳TB患的近期化疗结局与39个有关因素之间的关系，利用向前逐步选择法进行分析，按α=O．05的水平，拟合回归预测模型，并以回代检验方法考察模型的预测效能。结果：最终似合的方程为P=1／{1 exp[-(3．4773-0．1499X11-O．7983X23-0．150lX37)]}，回代检验的符合率为77.37％。结论：利用成组资料的非条件Logistic回归分析建立抗TB化疗结局的解释和预测模型是可行的．     

对氨基苯甲酸酯形成P450-MI络合物的分子轨道法研究

目的：研究对氨基苯甲酸醇同系物与大鼠肝微粒体形成细胞色素P450(P450)代谢中间体络合物(P450-MI)的初速率和分子轨道指数的相关性。方法：用半经验分子轨道MNDO—PM3法计算得到这些同系物的分子轨道指数,并用逐步多元回归分析法导出初速率的对数值(1og v)与分子轨道指数之间的相关方程式．结果：log v与最高占据分子轨道能级、最低未占据分子轨道能级、前抬电荷密度和氨基氮原子上的净电荷等分子轨道指数没有明显的相关性,而与分子总能量(ET)、亲电超离域度之和(∑SE)、原子净电荷绝对值之和(∑Q)等分子轨道指数具有很好的抛物线型相关性。结论：可以用ET、∑SE和∑Q等分子轨道指数预测对氨基苯甲酸酯与大鼠肝微粒体形成P450-MI络合物的初速率。     

从分子极性表面积预测头孢菌素类药物的血浆蛋白结合率

目的:采用分子结构参数预测头孢菌素类药物的血浆蛋白结合率。方法:用半经验自洽场分子轨道AM1法得到药物分子的优化几何构型,用Monte Carlo法计算分子极性表面积,相关分析采用逐步多元回归分析法。结果:头孢菌素类药物的血浆蛋白结合率(fb)与分子量(MW)和氢键给体表面积(SH)具有良好的相关性,回归方程式为:fb=0.5057 2.861×10-3MW-0.1572SH 4.714×10-3SH2(n=22,r=0.9042)。结论:头孢菌素类药物的血浆蛋白结合率不仅与药物的脂溶性,而且还与形成氢键的能力密切相关。从药物的分子量和极性表面积可以预测头孢菌素类药物的血浆蛋白结合率。     

人乳腺癌中3种耐药基因产物的表达及其与预后的相关性

目的研究多药耐药基因产物Pα糖蛋白(P-gP)、谷胱甘肽-S-转移酶π(GST-π)和DNA拓扑异构酶Ⅱα(TopⅡα)在乳腺癌组织中的表达及其与预后指标的关系。方法采用免疫组织化学技术,检测105例乳腺癌中P-gP、GST-π和TopⅡα耐药基因蛋白。结果(1)105例乳腺癌中P-gP、GST-π和TopⅡα的阳性表达率分别为77．1％、76．2％和36．2％;(2)P-gP及GST-π高表达和TopⅡα的低表达与肿瘤的浸润性和腋窝淋巴结转移相关;(3)P-gp、GST-π和TopⅡα与C-erbB-2的表达显著正相关;(4)GST-π与ER、PR的表达呈负相关。结论P-gp、GST-π和TopⅡα在乳腺癌的表达与其预后指标存在一定的联系,对乳腺癌患者在化疗前进行耐药基因检测,有助于判断预后及选择合理的化疗方案,从而提高疗效。     

整合素αVβ5在卵巢上皮性癌中的表达及临床意义

目的：探讨整合素αVβ5在卵巢上皮性癌中的表达及其与微血管密度(microvessel density,MVD)和临床病理特征的关系。方法：采用免疫组织化学PV两步法,分别测定15例正常卵巢组织、15例良性卵巢上皮性肿瘤、10例交界性卵巢上皮性肿瘤、57例卵巢上皮性癌组织中整合素αVβ5的表达及MVD。结果：(1)卵巢上皮性癌中整合素αVβ5的阳性率及MVD值高于正常卵巢组织、良性卵巢上皮性肿瘤和交界性卵巢上皮性肿瘤(P＜0.01);(2)卵巢上皮性癌中整合素αVβ5的阳性率及MVD值随临床分期、组织分级的升高而增加(P＜0.05);(3)卵巢上皮性癌中整合素αVβ5的表达强度与MVD值之间呈正相关(r=0.545,P＜0.05);(4)卵巢上皮性癌中整合素αVβ5表达阳性组患者的生存率明显低于整合素αVβ5表达阴性组(P＜0.05)。结论：整合素αVβ5可能通过介导血管新生参与卵巢上皮性癌的发生、发展、侵袭和转移,整合素αVβ5是卵巢上皮性癌患者的不良预后指标。     

癌光啉静脉滴注后的临床药物动力学研究

本文报道用荧光分光光度法测定11例恶性肿瘤病人静脉滴注癌光啉(PSD-007)后的药物动力学特性,药物剂量为4～4.5mg/kg体重,静滴速度每公斤体重0.1mg/min。 根据药-时曲线和Akaike信息判据(AIC)最小准则,确定最佳房室数目为开放三室模型,应用阻尼非线性最小二乘法计算程序,得:t_1/_2π=0.36±0.05h t_1/_2α=4.52±1.04h t_1/_2β=32.0±5.31h 此外测定了一例病人小剂量(1.82mg/kg)静滴后的药物动力学参数,亦以三室模型拟合为宜。     

配合物[Cu(bipy)(naph)(ClO4)]的合成及晶体结构

目的:设计合成化合物[Cu(bipy)(naph)(ClO4)],并测定其晶体结构。方法:通过牛磺酸缩β-萘酚醛与高氯酸铜()、2,2'-联吡啶合成并获得其单晶,通过X射线单晶衍射的方法测定了其晶体结构。结果:该晶体属三斜晶系,Mr=490.34,P1空间群。晶胞参数为:a=9.274(1),b=9.961(1),c=10.767(1);α=85.21°,β=82.567°,γ=80.939°,V=972.02(19)3,Z=2,F(000)=498,Dc=1.675Mg/m3,μ=1.305mm-1,最终结构偏离因子R=0.0270,ωR=0.0736,ω=1/[S2(F20) (0.0453P)2 0.0659P],P=(F2O 2FC2)/3。结论:配合物是五配位的变形四方锥构型。配合物通过氢键和芳环л-л堆积作用形成二维层状结构。     

治疗复杂性后尿道狭窄3种手术入路的比较解剖学研究

OBJECTIVE: To evaluate the advantages and disadvantages of 3 surgical approaches via superior intermedial margin of the pubis, inferior medial margin of the pubis, and the perineum, respectively, in the treatment of posterior urethral stricture. METHODS: Thirty-five adult male corpses were dissected in which the distances from the bulbo-membranous urethra conjunction (D), the apex of prostate (E), and the bladder neck (F) to the superior medial margin of the pubis (A), the inferior medial margin of the pubis (B) and the midpoint of linear distance between the two ischial tuberosities on the perineum (C) were respectively measured and compared. Another 20 adult male corpses were subjected to the 3 surgical approaches as described above and the urethra was exposed to identify the tissues and organs with possible injuries resulted from the surgery, which were evaluated by scoring. RESULTS: The distances measured were as follows: AD=6.5+/-0.5 cm, BD=2.2+/-0.5 cm, CD =3.4+/-0.6 cm, and BD0.05, t=0.13). The angles FAE (beta(1)) =(22.7+/-2.6)(degrees), FBE (beta(2))=(32.9+/-6.4)(degrees), FCE (beta(3))=(15.0+/-3.2)(degrees), and beta(2) beta(1) beta(3) (P=0.05, SNK means). The score for tissue and organ injuries for the approach of the superior medial margin of the pubis was 13, 20 for the approach of inferior medial margin of the pubis, and 15 for perineum approach. CONCLUSIONS: In terms of operative field exposure, the best operation approach is via the inferior pubis, followed by superior pubis approach and perineum approach; while in view of the injuries, superior pubis approach is better than the perineum and inferior pubis approaches. The inferior pubis approach should be the primary choice in the treatment of posterior urethral stricture.     

莨菪烷衍生物的合成及其对大鼠气管的拮抗活性和组织选择性

目的 合成系列莨菪烷衍生物,评价其对大鼠气管的拮抗活性及组织选择性（气管/心脏）。方法 以3α-羟基-6β-乙酰氧基莨菪烷（A0）为起始物,通过酰化反应合成系列3α-酰氧基-6β-乙酰氧基莨菪烷。分别选取含丰富M2、M3受体并由其介导收缩的大鼠心脏（M2）和气管平滑肌（M3）为测试样本,通过组织功能实验,测试合成物对大鼠离体心脏和气管的拮抗活性。结果 制备8个莨菪烷衍生物,A1~A4对心脏和气管有明显拮抗作用,A5~A8对心脏和气管无拮抗活性。A1对气管的拮抗参数pA2值最大（pA2= 7.32）,且有较高的组织选择性（气管/心脏）（ΔpA2=1.51）。结论 减小莨菪烷母核的C-3α位苯环上取代基的体积或增加苯环上π电子云的密度,对提高化合物拮抗气管的活性及组织选择性（气管/心脏）有利。     

Percutaneous vertebroplasty using instruments and drugs made in China for vertebral metastases

Objectives To evaluate the effect of percutaneous vertebroplasty on vertebral tumor metastasis using instruments and drugs made in China and to explore the technique of percutaneous vertebroplasty.Methods Thirty-two patients with vertebral metastasis were treated with percutaneous vertebroplasty with instruments and drugs made in China. Anterolateral approach for cervical vertebrae and transpedicular approach for thoracic and lumbar vertebrae were used. The volume of disease focus and the amount of polymethy methacrylate (PMMA) injected were calculated with formula V =4/3π(D/2) …^3 preoperatively. PMMA with contrast was mixed according to the ratio of powder/liquid/contrast of 3:2:1. The procedures were monitored under fluoroscopy. PMMA was injected in the polymerization time. CT scanning was performed before and after the operation.Results The percentage of lesion PMMA fill was more than 50% as demonstrated by CT. Clinical data were obtained from the cases followed up for 7 - 12 months, and the rate of pain relief was 90. 6% (29/32) at one week, 71.8% (23/32)at six months, and 58.6%(17/29)at 12 months after operation. There were no cases of PMMA leakage that affected clinical performance.Conclusions Percutaneous vertebroplasty for vertebral tumor metastasis using instruments and drugs made in China was effective. It is important to prevent paravertebral leaks of PMMA and to ensure that PMMA is injected within the polymerization time.     

Expression of integrin alpha v beta 6 in rats with ventilator-induced lung injury and the attenuating effect of synthesized peptide S247.

BACKGROUND: High tidal volume ventilation can cause inflammatory reaction in lungs. Integrins are associated with regulating lung inflammation and edema following acute lung injury. Integrin alpha v beta 6 expression in ventilator-induced lung injury (VILI) and the ability of the RGD-peptidomimetic agent S247 to attenuate VILI in rats were investigated. MATERIAL/METHODS: Eighteen adult male rats were assigned to three groups: controls (C: n=6) with no ventilation; high tidal volume lung ventilation (H: n=6); and such ventilation after treatment with S247 (HS: n=6). HS was injected with 50 mg/kg S247 18 h before and then i.p injection every 3 h until the start of ventilation. The others received saline. Assessed were lung histopathology, wet-to-dry weight ratios, total protein content, white blood cell (WBC) counts, macrophage inflammatory protein-2 (MIP-2), and tumor necrosis factor-alpha (TNF-alpha) concentrations in the bronchoalveolar lavage fluid (BALF) and integrin alpha v beta 6 mRNA and protein expression. RESULTS: Wet-to-dry weight ratios and BALF WBCs and total protein content were different among the groups (p<0.01). Lung injury score and integrin alpha v beta 6 mRNA level were lower in HS than in H (p<0.01). Integrin alpha v beta 6-positive staining was mainly on alveolar walls and the immunoreactivity of HS was clearly less than in H. TNF-alpha was not detected in C and was significantly lower in HS than in H (p<0.05). MIP-2 concentration in H was higher than in C and HS (p<0.01). CONCLUSIONS: Pretreatment with S247 attenuated VILI, suggesting pulmonary epithelial integrins are involved in its pathogenesis and agents such as S247 may be useful in treating it.     

人类白细胞抗原-DRβ1特异性低T细胞反应性肽对T细胞激活的抑制作用

目的　研究人类白细胞抗原 (HLA) DRβ1特异性Ⅱ型胶原 (CII)多肽的T细胞受体(TCR)结合表位改变对T细胞激活的影响。探讨通过抑制T细胞对抗原肽的识别治疗类风湿关节炎的新途径。方法　利用AutoDock3 0系统设计非T细胞结合肽 ;以激光共焦显微镜及流式细胞仪观察荧光标记的CⅡ 2 6 3 2 72修饰肽的细胞内转运及其在细胞膜上的表达 ;应用HLA DR1转基因抗原呈递细胞和特异性T细胞的激活体系 ,研究替换TCR识别氨基酸的CII修饰肽在T细胞激活中的作用。结果　计算机模拟显示CII第 2 6 3位苯丙氨酸 (F)、2 6 6位谷氨酸 (E)是与HLA DR1结合的关键位点 ,而 2 6 7位谷氨酰胺 (Q)、2 6 9位脯氨酸 (P)和 2 70位赖氨酸 (K)是T细胞识别的主要功能氨基酸。用甘氨酸 (G)、和 /或丙氨酸 (A)替换上述位点可去除功能性侧链。CⅡ修饰肽可被HLA DR1转基因抗原呈递细胞摄取并与膜表面的HLA DR1分子结合。CⅡ 2 6 3 2 72原型肽可激活T细胞 ,而用A或G单一替换 2 6 7、2 6 8、2 6 9、2 70位氨基酸或连续替换 2 6 8 2 70位氨基酸的修饰肽对T细胞的激活能力明显降低 (P <0 0 1)。低反应性修饰肽 2 70A、sub2 6 8 2 70对CⅡ诱导的T细胞激活有显著抑制作用。结论　通过替换CII中TCR特异性氨基酸可减弱或消除其对T细胞的结合能力及激     

原发性高血压与心脏β2、α1及AT1受体自身抗体的关系

目的探讨抗G-蛋白偶联型β2、α1及AT1受体的自身抗体在原发性高血压病程中的分布情况。方法应用酶联免疫吸附测定(ELISA)技术,以细胞外第二环表位肽段的合成肽作为抗原,检测50例高血压心脏病、40例单纯高血压和40例正常人血清中抗G-蛋白偶联家族中β2、α1和AT1受体的自身抗体。结果高血压心脏病患者血清中抗G-蛋白偶联型β2、α1和AT1受体自身抗体的阳性率明显高于单纯高血压和正常组(P<0.05);高血压心脏病自身抗体阳性的平均几何滴度与单纯性高血压比较无明显差异(P>0.05),但两组阳性抗体的平均几何滴度均明显高于正常组。高血压心脏病抗β2受体自身抗体阳性患者中,81.0%同时具有α1受体的自身抗体,76.2%同时具有AT1受体的自身抗体,52.4%存在上述3种受体的自身抗体。结论抗G-蛋白偶联型β2、α1及AT1受体的自身抗体参与原发性高血压的病理生理过程,可能与心肌和血管重构有关。     

“十二五”期间门诊人次和住院人数的预测

目的预测我院门诊人次和住院人数,为制定＂十二五＂各项计划提供理论依据。方法用时间数列指标平均增长量和回归直线方程进行预测。结果通过方差分析得到前十年门诊人次和住院人数P〈0.01,线性关系显著。从而得到门诊人次预测模型为：Y=141.124＋20.742t,出院人次预测模型为：Y=4.524＋0.776t,得到预测年的点预测值和区间预测值。即在各种条件相对稳定的情况下平均每年分别增加20,742人次和776人。结论回归直线方程进行预测,是统计理论在实际工作中的应用,具有较好的实用性。     

儿童青少年血浆新型气体信号分子硫化氢的参考值

目的 测定儿童与青少年血浆硫化氢含量的参考值.方法 健康儿童青少年200名,按照其年龄与性别分组,7～14岁75名(男43名,女32名),15～19岁125名(男64名,女61名),应用敏感硫电极法测定血浆硫化氢(H2S)含量.结果 学龄期7～14岁男孩血浆H2S含量为(52.2181±17.9400)μmol/L,女孩H2S含量为(51.9441±16.5448)μmol/L;15～19岁男孩血浆H2 S含量为(52.8771±14.1444)μmol/L,女孩H2 S含量为(53.6551±14.5563)μmol/L.各年龄组间及性别间差异均无显著性(P＞0.05),合并统计后得出儿童青少年血浆H2S含量的浓度均值为(52.8234±15.4339)μmol/L.结论 儿童青少年血浆H2S含量参考值为(52.8234±15.4339)μmol/L.