肺奴卡菌病合并肺孢子菌感染1例并文献复习

目的探讨肺奴卡菌合并肺孢子菌感染的临床表现、诊断和治疗。方法对1例肺奴卡菌肺炎合并孢子菌感染患者的临床资料进行分析并复习相关文献。结果患者存在糖尿病,存在免疫功能低下。肺部影像呈现浸润坏死改变;气管镜下见化脓坏死及肉芽增生;组织病理和痰液六胺银染色证实肺奴卡菌和孢子菌;经SMZ-CO治疗肺部病灶明显吸收好转。结论对存在免疫功能低下的患者,出现肺部化脓性病变,一般抗菌药物治疗无效的情况下,需警惕奴卡菌感染的可能。早期细菌学检查,有利于疾病早期诊断、早期治疗,达到最佳预后。     

曲霉合并耶氏肺孢子菌肺部感染1例并文献复习

曲霉合并肺孢子菌肺部感染报道少见,主要发生于免疫功能低下的患者,其临床诊断困难,死亡率高。本文报道了1例曲霉菌合并耶氏肺孢子菌肺部感染病例的诊治经过,并检索国内外相关文献,对检索到的12例病例及本例患者的临床症状、影像学表现、诊断方法、治疗手段等进行梳理、分析及总结,以期为临床医生诊治该类疾病提供一定思路。     

免疫检查点抑制剂治疗期间并发肺孢子菌感染：两例病例报道并文献复习

近年来,免疫检查点抑制剂（ICI）在临床中广泛应用,给肿瘤患者带来了比放疗、化疗更进一步的生存获益。然而,在免疫抑制剂增强细胞免疫抗肿瘤的同时,也有可能增强机体正常的免疫反应,导致机体免疫耐受紊乱,引起相应器官出现不适症状,称之为免疫相关不良反应。其中,免疫相关性肺炎往往较难诊断,严重者可致命。肺孢子菌肺炎（PCP）作为一种机会性真菌感染性疾病,常发生于免疫力低下人群。鉴于ICIs对免疫功能的促进作用,目前的主要观点认为,肿瘤免疫治疗并不会增加肺孢子菌感染的机会。本文报道了两例免疫治疗期间发生肺孢子菌感染的病例,以期进一步加深人们对免疫相关性肺炎及PCP的认识。     

卡泊芬净治疗免疫缺陷合并耶氏肺孢子菌肺炎患者一例

本文报道1例既往因慢性间质性肾炎长期口服甲泼尼龙导致细胞免疫功能下降的非HIV感染的重症肺炎患者,在支气管肺泡灌洗液标本中经宏基因组二代测序检测到耶氏肺孢子菌及结核杆菌。由于患者对磺胺类药物过敏,且其他二线治疗药物短期内无法获得,故选择单用卡泊芬净50 mg静脉滴注治疗耶氏肺孢子菌肺炎（PJP）。4 d后,患者的感染症状、实验室检查结果、胸部CT及X线片检查均显示病情得到改善,提示单用卡泊芬净抗感染治疗PJP有效。     

经肺泡灌洗液高通量基因检测对膀胱癌患者术后耶氏肺孢子菌感染的诊断及其临床治疗分析

目的:分析经肺泡灌洗液高通量基因检测对膀胱癌患者术后耶氏肺孢子菌感染的诊断及其临床治疗,为耶氏肺孢子菌感染的诊断和治疗提供参考.方法:对1 例因膀胱癌化疗后出现药物性肝损害患者,在服用糖皮质激素治疗的过程中被诊断为耶氏肺孢子菌肺炎患者的临床资料,分析其临床诊断与治疗方法的合理性.结果:患者入院后,根据其发热、干咳、低氧血症的特点,及时行支气管镜采集肺泡灌洗液高通量基因测序,被诊断为肺孢子菌感染,予以复方磺胺甲噁唑片抗感染治疗21 d,临床症状明显好转,肺部影像学提示炎症基本吸收.结论:耶氏肺孢子菌肺炎患者给予复方磺胺甲噁唑治疗可有效改善其临床症状;对于非HIV感染者的肺孢子菌肺炎也可采用肺泡灌洗液高通量基因测序,以协助肺孢子菌肺炎的诊断与治疗.     

经肺泡灌洗液高通量基因检测对膀胱癌患者术后耶氏肺孢子菌感染的诊断及其临床治疗分析

目的:分析经肺泡灌洗液高通量基因检测对膀胱癌患者术后耶氏肺孢子菌感染的诊断及其临床治疗,为耶氏肺孢子菌感染的诊断和治疗提供参考.方法:对1 例因膀胱癌化疗后出现药物性肝损害患者,在服用糖皮质激素治疗的过程中被诊断为耶氏肺孢子菌肺炎患者的临床资料,分析其临床诊断与治疗方法的合理性.结果:患者入院后,根据其发热、干咳、低氧血症的特点,及时行支气管镜采集肺泡灌洗液高通量基因测序,被诊断为肺孢子菌感染,予以复方磺胺甲噁唑片抗感染治疗21 d,临床症状明显好转,肺部影像学提示炎症基本吸收.结论:耶氏肺孢子菌肺炎患者给予复方磺胺甲噁唑治疗可有效改善其临床症状;对于非HIV感染者的肺孢子菌肺炎也可采用肺泡灌洗液高通量基因测序,以协助肺孢子菌肺炎的诊断与治疗.     

中西医结合治疗大鼠卡氏肺孢子菌肺炎的实验研究

目的 探讨中药方剂和复方磺胺甲基异恶唑（SMZCO）针剂联合治疗卡氏肺孢子菌肺炎大鼠模型的疗效.方法 选用SD大鼠,设置正常对照组4只,利用地塞米松注射法,复制SD大鼠卡氏肺孢子菌肺炎模型并按随机数字法分为：卡氏肺孢子菌肺炎模型组9只,SMZCO治疗组9只,中药方剂治疗组9只,中药方剂联合SMZCO治疗组9只.酶联免疫分析法检测各组大鼠肺泡灌洗液中白细胞介素8（IL-8）、肿瘤坏死因子α（TNF-α）和血清乳酸脱氢酶（LDH）含量;六胺银染色观察肺组织印片肺孢子菌包囊,光镜和电镜观察肺组织病理学和超微结构变化.结果 5组间肺泡灌洗液的IL-8、TNF-α水平总体方差分别为8.97、10.23,P值为0.038、0.031,其总体差异有统计学意义.在治疗组中,中药方剂治疗组IL-8水平较高[（476±45） μg/L],中药方剂联合SMZCO治疗组最低[（302±18） μg/L],差异有统计学意义（P＜0.05）.5组间LDH水平总体差异有统计学意义（P =0.036）.同SMZCO治疗组比较,中药方剂治疗组LDH水平[（184 ±56） U/L]较高,中药方剂联合SMZCO治疗组[（96±35） U/L]最低,差异有统计学意义（均P＜0.05）.SMZCO治疗组、中药方剂治疗组、中药方剂联合SMZCO治疗组的肺孢子菌包囊减少率分别为85.5％、15.2％和90.3％,差异有统计学意义（P＜0.05）.与SMZCO治疗组比较,中药方剂联合SMZCO治疗组肺间质炎性细胞浸润明显减少,肺泡及间隔修复基本完整,肺组织结构接近正常,肺孢子菌包囊明显减少.电镜观察模型组的肺组织可见肺泡上皮细胞变性脱落,基底膜暴露,间质胶原纤维增生,肺泡腔内蛋白渗出增多.肺孢子菌虫体与肺泡上皮细胞紧密接触.结论 中药方剂对卡氏肺孢子菌肺炎大鼠模型的虫体、炎性因子等有一定抑制作用,可改善肺泡上皮损伤,与SMZCO联合使用有较好疗效.     

艾滋病合并耶氏肺孢子菌肺炎76例临床分析

耶氏肺孢子菌肺炎（pneumocystis carinii pneumonia,PCP）是由耶氏肺孢子菌（pneumocystis carinii,PC）引起的呼吸系统机会性感染,发病率达86%。60%的患者是以PCP就诊而确诊的AIDS疾病,同时也是AIDS患者易反复发作的疾病（PCP）,常伴有肺部其他机会性感染而加重病情,机体多系统损害,最终导致呼吸衰竭,为AIDS患者主要死亡原因。AIDS合并PCP如能重视,早诊治是可以控制的,甚至可以治愈。     

两肺弥漫磨玻璃样影伴免疫功能缺陷患者的临床诊疗体会

目的：提高临床对出现两肺弥漫磨玻璃样影患者可能伴免疫功能缺陷疾病的认识。方法回顾分析2013年4月～2013年12月呼吸科ICU收治的6例胸部CT平扫见两肺弥漫磨玻璃样影,伴发热、气促、低氧血症患者的诊治过程。结果6例患者确定均合并免疫功能缺陷。其中5例HIV抗体检测阳性,1例为溃疡性结肠炎长期口服免疫抑制剂患者,6例患者经口服复方新诺明等治疗后均效果明显,其中2例支气管灌洗液找到肺孢子菌滋养体。结论胸部影像见两肺弥漫磨玻璃样影患者可能合并免疫功能缺陷,其中以艾滋病患者并发肺孢子菌肺炎常见,建议对长期发热、咳嗽少痰、气促、胸部影像学呈弥漫性损害的患者将HIV抗体血清学检测作为就诊的常规检测指标,以提高HIV感染的诊断率。     

聚合酶链反应检测肺孢子菌的实验研究

目的探讨应用改良传统三步聚合酶链反应(PCR)方法检测肺孢子菌DNA的意义。方法选择Wistar大鼠40只,随机分成实验组和对照组各20只。实验组每周2次皮下注射地塞米松,诱导产生肺孢子菌;对照组注射等剂量的生理盐水。8周后,收集大鼠肺组织和支气管肺泡灌洗液(BALF),分别用三步法与两步法PCR技术检测肺孢子菌DNA,并与Giemsa染色法比较。结果 PCR方法检测肺泡灌洗液中肺孢子菌DNA的方法敏感性(70%)明显高于常规染色法(30%)(P<0.05),且敏感度93%、特异度100%、阳性预测值100%、阴性预测值83%。实验组中PCR检测肺组织和支气管肺泡灌洗液的肺孢子菌DNA阴性者,Giemsa病原染色法亦为阴性。实验组大鼠的肺组织与支气管肺泡灌洗液分别行传统三步法与二步法PCR检测,2种检测方法阳性率相同,分别为80%和70%,差异无统计学意义(P>0.05)。对照组大鼠各种方法检测均为阴性。结论两步法PCR可作为早期诊断肺孢子菌肺炎(PCP)的方法,可用于BALF中检测肺孢子菌DNA,其敏感度、特异度、阳性预测值和阴性预测值均很高,易于临床推广应用。     

Effects of cannabidiol and of diphenylhydantoin on the hippocampus and on learning

Cannabidiol (3.5 mg/kg, i.p.) depressed hippocampal facilitation and posttetanic potentiation of evoked responses in rats, such, as had been reported before for diphenylhydantoin. Both diphenylhydantoin (80 mg/kg, i.p.) and cannabidiol blocked the increase of hippocampal RNA concentration caused by afferent stimulation, and depressed the acquisition of a conditioned avoidance response in rats. Neither drug affected the retention of such response when given by posttrial injection, nor the spontaneous locomotor activity of mice. The effects of both agents may be explained by the interference they have been previously shown to produce with the release of K⁺ from the hippocampus during stimulation. In fact, hippocampal facilitation and posttetanic potentiation and the RNA response to stimulation have been shown to be phenomena which depend on this K⁺ release, and have been attributed a role in learning.     

β3-肾上腺素受体激动剂的研究进展

摘要β     

妊娠合并子宫肌瘤对母儿影响的分析

目的 探讨妊娠合并子宫肌瘤对母儿的影响。方法 对1999年1月～2004年12月73例在剖宫产术中发现的子宫肌瘤进行分析。结果 妊娠合并肌瘤的胎位异常（臂位）率、产后出血率分别为17．8％、20．54％,而对照组分别为3．18％和8．97％;低体重儿发生率12、33％,而对照组为6．07％,有显著差异。结论 子宫肌瘤增加了母儿并发症的可能性;合并黏膜下肌瘤也有望使妊娠过程成功。     

朱砂及含朱砂制剂的肝肾毒性研究

目的 探讨朱砂、含朱砂制剂（柏子养心片）及甲基汞对大鼠的体内外毒性,为其临床安全用药提供科学依据。方法 ①对比甲基汞、朱砂及柏子养心片体外对人肝HL-7702细胞和人肾近曲小管上皮HK2细胞的毒性,计算半数抑制浓度（IC₅₀）。②SD大鼠随机分为对照组,朱砂组0.1 g/kg,柏子养心片0.2、0.4、0.8 g/kg组,甲基汞组0.001 g/kg,每天ig 1次,连续给药90 d后,取血及肝、肾组织;试剂盒法检测血清中丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、肌酐（CREA）、尿素氮（BUN）水平,测汞仪固体直接进样法检测肝、肾组织中汞蓄积量,并对大鼠肝脏和肾脏做组织病理学检查。结果 体外试验表明,朱砂、柏子养心片及甲基汞对HL-7702细胞的IC₅₀分别为7.852、6.035、0.009 5 g/L;对HK2细胞的IC₅₀分别为6.297、4.484、0.008 9 g/L。亚慢性毒性试验表明,甲基汞组大鼠肝、肾组织中汞蓄积量及血清中ALT、AST、CREA、BUN值均显著高于对照组,而朱砂及柏子养心片（高、中、低剂量）组与对照组比较均没有显著性差异;甲基汞组大鼠肝脏呈现肝细胞变性,肾脏可见明显肾小管损伤,而朱砂及柏子养心片（高、中、低剂量）组与对照比较没有明显差异。结论 朱砂及柏子养心片的体内外毒性均显著低于甲基汞,在目前药典规定的临床用量下使用安全性较好。     

Effects of raunescine and isoraunescine on behaviour and on the 5-hydroxytryptamine and noradrenaline contents of brain

Some behavioural effects of raunescine and isoraunescine on pigeons have been studied; no qualitative difference was detected between their effects and those of reserpine. Isoraunescine is between five and ten times less potent than raunescine, which, in turn, is much less potent than reserpine in producing these effects.

Both raunescine (5 mg./kg.) and isoraunescine (50 mg./kg.) were found to cause a reduction in the concentration of noradrenaline in the brains of rats. Raunescine (5 mg./kg.) also caused a reduction in the concentration of 5-hydroxytryptamine in brain; isoraunescine did not do so in the same dose; higher dose levels were not studied.

     

Effect of ranitidine on ileal myenteric plexus preparation and on acetyl- and butyrylcholinesterase

Ranitidine at concentrations from 1 microM to 0.1 mM brought about a dose-dependent potentiation of the twitch responses elicited by electrical stimulation of the ileal myenteric preparation. At higher concentrations (0.3-3 mM) ranitidine also caused irregular slow contractions of the unstimulated ileal preparation which were potentiated by eserine and blocked by atropine and tetrodotoxin. In order to identify the mechanism of these apparently cholinomimetic actions, the effects of ranitidine on AChE and BuChE were studied. Ranitidine showed an instantaneous and promptly reversible inhibitory action at concentrations between 0.5 and 30 microM. Double reciprocal plots were prepared and equilibrium dissociation constants calculated. It appears that ranitidine exerts an inhibition of the "mixed" type on both AChE and BuChE, but the dissociation constants for BuChE were markedly higher than those for AChE. Since AChE inhibition occurs in the same concentration range potentiating the twitch responses on the ileal myenteric preparation, it may explain the cholinomimetic effect of ranitidine.     

新药研发成本评估的必要性与现实性初探

目的探讨开展新药研发成本预测的必要性与现实性。方法综合国内外行业报告数据,寻求成本发展趋势,表明成本预测的必要性;列举成本预测方法,阐释成本预测的现实性。结果国内企业药品研发成本控制环节比较薄弱,目标成本不明确,导致资金浪费,需要建立成本预测体系。结论新药研发项目成本预测体系的建立是成本管理的基础,会使资金运营更合理,为压缩成本寻求途径;企业明确目标成本及研发投入与产出,将获得更强的研发动力。     

高血糖、高胰岛素对内皮细胞凋亡及Mn-SOD表达的研究

目的：了解糖尿病高胰岛素及高血糖的改变对内皮细胞凋亡及Mn-SOD表达的影响。方法：在高糖、高胰岛素及对照培养环境,分别孵育内皮细胞72h测定细胞凋亡情况并检测Mn-SOD的表达水平。结果：内皮细胞在高糖、高胰岛素条件下凋亡显著增加（P〈0.05）,同时Mn-SOD表达下降（P〈0.05）。结论：在高胰岛素血症而血糖没有升高到糖尿病标准的阶段,就会有内皮细胞凋亡显著增加,从而促进动脉粥样硬化形成,同时还有Mn-SOD表达水平的下降,病损持续存在于2型糖尿病进展的各个阶段。     

Effect of sodium diclofenac on serum and tissue concentration of amoxicillin and on staphylococcal infection

The effect of sodium diclofenac on serum and tissue amoxicillin concentration as well as their effect against staphylococcal infection was observed. Four polyurethane sponges were placed in the back of thirty rats. After 14 d, two granulomatous tissues received 0.5 ml of 10(8) cfu/ml (Staphylococcus aureus). Two days later, the rats were divided into five groups: group 1 received amoxicillin 50 mg/kg/p.o., group 2 received amoxicillin 25 mg/kg/p.o., group 3 received sodium diclofenac 2.5 mg/kg/i.m. and amoxicillin 50 mg/kg/p.o., group 4 received sodium diclofenac 2.5 mg/kg/i.m., and group 5 (control group) received NaCl 1 ml/p.o. After six hours of drug administration, blood serum (10 microl) and noninfected granulomatous tissues were placed on Mueller-Hinton agar inoculated with 10(8) cfu/ml (S. aureus). Infected tissues were dispersed in a sonic system and were spread (10 microl) on salt mannitol agar. Microorganisms were counted and the inhibition zones were measured after 18 h of incubation at 37 degrees C. Amoxicillin tissue concentration was 6.27 microg/g for group 1, 2.18 microg/g for group 2, and 0.72 microg/g for group 3. The serum concentrations were 11.56 microg/ml for group 1, 5.36 microg/ml for group 2, and 1.34 microg/ml for group 3. No differences were observed among group 1, 2, and 3 regarding staphylococci counts (Kruskall-Wallis test p>0.05). Group 4 reduced (p<0.05) staphylococci counts comparing to group 5. It was concluded that sodium diclofenac reduced serum and tissue amoxicillin concentration and, even in large doses, amoxicillin was not effective in eradicating the staphylococcal infection after 6 h of administration.     

Effects of H-Phe-Ile-Tyr-His-Ser-Tyr-Lys-OH on passive and active avoidance behavior and on open-field activity of rats

The action of H-Phe-Ile-Tyr-His-Ser-Tyr-Lys-OH on the passive and active avoidance behavior and open-field activity of rats was studied after peripheral and intracerebroventricular administration. When applied before the test session, intracerebroventricular administration increased the avoidance latency of passive avoidance behavior. Subcutaneous, intraperitoneal and intracerebroventricular administration of the peptide delayed the extinction of active avoidance behavior. Both subcutaneous and intracerebroventricula administration increased the grooming activity of the rats. The data suggest that H-Phe-Ile-Try-His-Ser-Tyr-Lys-OH is able to influence memory, acting mainly on the retrieval processes, ad to modify open-field activity.