急性脑出血大鼠肠系膜淋巴结IRAK-4、CD14 mRNA的表达与肠道屏障损伤的关系及星蒌承气汤的干预研究

目的:研究白细胞分化抗原14(CD14),白细胞介素-1受体相关激酶-4(IRAK-4)活性在急性脑出血痰热腑实证肠内内毒素信号转导通路的作用,以及星蒌承气汤的干预作用。方法:采用大脑注射Ⅶ型胶原酶法建立SD大鼠急性脑出血模型,随机分为正常组,脑出血组,脑出血痰热腑实证组,星蒌承气汤组,每组分24h,48h,72h3个时相亚组,实时荧光定量PCR观察肠系膜淋巴结组织CD14、IRAK-4 mRNA表达,并观察结肠HE染色结果。结果:脑出血急性期肠系膜淋巴结组织CD14、IRAK-4 mRNA mRNA表达升高,星蒌承气汤能明显减轻结肠组织病理损伤。结论:CD14、IRAK-4 mRNA在介导急性脑出血内毒素信号转导中起重要作用,为肠道屏障损伤重要因素,星蒌承气汤对脑出血急性期痰热腑实证结肠组织具有一定的保护作用。     

Upregulation of matrix metalloproteinase 14 (MMP14) is associated with poor prognosis in renal clear cell carcinoma—a bioinformatics analysis

BackgroundMatrix metalloproteinase 14 (MMP14) has been reported to be upregulated in some types of cancer and to promote cancer cell invasion and metastasis. However, the expression profile and functional role of MMP14 in kidney renal clear cell carcinoma (KIRC) remains unknown. This study investigated the association between MMP14 expression level and prognosis in KIRC.MethodsThe messenger RNA (mRNA) expression profile and clinical data (including T stage, N stage, M stage, pathologic stage, gender, race, age, histologic grade, serum calcium, hemoglobin) were obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database. Protein expression was evaluated by immunohistochemistry in the Human Protein Atlas (HPA) database. Correlation analyses between MMP14 and all mRNAs in KIRC were batch calculated, and gene set enrichment analyses (GSEA) were then conducted of Disease Ontology (DO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways using R packages. Multivariate logistic regression analysis was used to explore the prognostic factors of KIRC patients.ResultsThe gene expression of MMP14 was significantly upregulated in KIRC tissues when compared with the normal tissue (P<0.001). The predictive ability of MMP14 as a variable for predicting tumor and normal outcomes had certain accuracy based on the receiver operating characteristic (ROC) model [area under the curve (AUC) =0.881, confidence interval (CI): 0.844-0.917]. When compared with the normal kidney tissue, the protein expression of MMP14 in KIRC got an increased trend, but due to the limited sample size, the difference is not statistically significant (P>0.05). Survival analysis revealed that MMP14 was significantly associated with overall survival in KIRC (P=0.013). GSEA of DO terms indicated high expression of MMP14 was related to KIRC, and GSEA of KEGG pathways showed that MMP14 and its coexpressed genes were significantly positively correlated with pathways in cancer. Signaling pathway GSEA indicated the upregulation of MMP14 in KIRC may activate cancer pathways.ConclusionsMMP14 may be associated with poor prognosis in KIRC and may be a potential prognostic marker for KIRC.     

呼出气一氧化氮联合脉冲振荡检查在学龄前儿童哮喘中的诊断价值研究

目的探讨呼出气一氧化氮（fractional exhaled nitric oxide，FeNO）联合脉冲振荡（impulse oscillometry，IOS）肺功能检查对学龄前儿童哮喘的诊断价值，并建立最佳预测模型。方法回顾性纳入2019年9月至2020年12月收治的3~5岁喘息儿童156例，分为哮喘组（52例）和非哮喘组（104例）。对2组患儿的IOS参数、FeNO及临床资料进行分析比较，通过多因素logistic回归建立最佳预测模型。结果哮喘组频率5 Hz时呼吸系统总阻抗（respiratory system impedance at 5 Hz，Z5）、频率5 Hz和20 Hz时阻抗（resistance of respiratory system at 5 Hz and 20 Hz，R5和R20）、共振频率、电抗面积（reactance of area，AX）和FeNO水平均高于非哮喘组，频率5 Hz时电抗差值小于非哮喘组（P<0.05）。受试者工作特征曲线分析显示Z5、R5、R20和FeNO对哮喘诊断有价值（P<0.05）。多因素logistic回归分析建立的最佳预测模型为R20+AX+FeNO，其曲线下面积为0.858（P<0.05），灵敏度为78.8%，特异度为76.9%。结论FeNO联合IOS检查有助于学龄前儿童哮喘的诊断，由R20+AX+FeNO组成的模型在学龄前儿童哮喘的诊断中具有一定价值。     

骨髓增生异常综合征白血病转化危险因素研究

目的探讨骨髓增生异常综合征（MDS）白血病转化（LT）的危险因素。方法收集2012年 1月至2020年12月中国医学科学院血液病医院MDS诊疗中心确诊、具有完整的临床资料且进行LT情况随访的320例初诊的原发性MDS患者，回顾性分析发生LT的MDS患者初诊时临床和分子学特征以及MDS患者发生LT的危险因素。结果中位随访13.6（0.4～107.3）个月，随访期间共有75例（23.4％）MDS患者发生LT（LT组）。与未发生LT患者（未发生LT组）相比，LT组患者年龄更大（60岁对48岁，P<0.001）、骨髓原始细胞比例更高（7.0％对2.5％，P<0.001）。两组患者中骨髓纤维化（MF-2/3级比例）（13.9％对6.5％，P＝0.046）、WHO分型诊断构成比（P<0.001）、修订版国际预后积分系统（IPSS-R）分组（P<0.001）和IPSS-R细胞遗传学分组（P＝0.001）比较，差异均有统计学意义。初诊时，LT组和未发生LT组患者中位基因突变数目分别为1（1，3）个、1（0，2）个（P＝0.003）。LT组TP53（P＝0.034）、DNMT3A（P＝0.026）、NRAS（P＝0.027）、NPM1（P＝0.017）基因突变率显著高于未发生LT组。6例患者初诊和LT时两次二代测序结果比较，LT时患者中位基因突变数目增多［2（0～8）个对0.5（0～4）个］，中位等位基因突变频率（VAF）较初诊时明显增加。多因素Cox分析显示，骨髓原始细胞比例［以<5％为参照，5％～10％的HR＝4.587，95％CI 2.214～9.504，P<0.001；>10％的HR＝9.352，95％CI 4.049～21.600，P<0.001］，IPSS-R细胞遗传学分组差和极差（HR＝2.603，95％CI 1.229～5.511，P＝0.012）、DNMT3A突变（HR＝4.507，95％CI 1.889～10.753，P＝0.001）、NPM1突变（HR＝3.341，95％CI 1.164～9.591，P＝0.025）是MDS发生LT的独立危险因素。结论骨髓原始细胞比例高、IPSS-R细胞遗传学分组差和极差、DNMT3A突变、NPM1突变是MDS发生LT的独立危险因素。     

细胞角蛋白14在牙齿软组织萌出通道中的组织学定位

目的牙齿萌出时,源于成釉器的缩余釉上皮与口腔上皮细胞融合为上皮团形成牙齿的软组织萌出通道,本研究对细胞角蛋白14在这一过程中的表达进行组织学定位,从而探讨其可能作用。方法不同发育期SPF级BALB/c小鼠9只。循环内固定后分别双侧下颌骨10%EDTA脱钙30d,常规脱水包埋,近远中向5μm连续切片,行苏木精-伊红和免疫组化染色。PV免疫组化两步法检测细胞角蛋白14和细胞增殖核抗原在各组织的表达。结果牙齿萌出过程中口腔上皮对细胞角蛋白14呈现时空特异性表达,非牙齿萌出部位的口腔上皮仅基底层阳性表达细胞角蛋白14,而萌出牙齿冠方的口腔上皮阳性表达则较广泛;缩余釉上皮在牙齿萌出过程中始终阳性表达细胞角蛋白14,而且伴随缩余釉上皮和口腔上皮融合的发生,缩余釉上皮的外层细胞和口腔上皮的基底层和基底上层细胞呈现细胞角蛋白14强阳性表达。结论细胞角蛋白14与牙齿萌出软组织通道的形成密切相关,可作为缩余釉上皮相关研究的上皮性标记物。     

口腔与胃幽门螺杆菌检测结果分析

目的:分析口腔与胃中幽门螺杆菌的检测结果,证明口腔HP可能是胃HP的一个重要储菌池.方法:采用快速尿素酶试验和14C尿素呼气试验相结合的方法,对132例OLP患者行口腔和胃黏膜幽门螺杆菌感染检测.结果:在OLP患者中,不论有无慢性胃病史,患者口腔幽门螺杆菌感染率均明显高于胃内幽门螺杆菌感染率;有慢性胃病史的患者,胃和口腔中幽门螺杆菌感染率为76.19%和96.83%;无慢性胃病史的患者,胃和口腔中幽门螺杆菌感染率为31.88%和57.97%.结论:口腔HP与胃HP感染密切相关,它可能是胃HP的一个重要储菌池.     

Bioactivity-directed isolation, identification of diuretic compounds from Polyporus umbellatus

Aim of the study

Polyporus umbellatus is a fungus used as a diuretic medicine. The objective of this study was to isolate and elucidate the diuretic constituents of n-hexane, ethyl acetate, n-butanol and water extracts of Polyporus umbellatus and to evaluate their diuretic activity.

Materials and methods

The n-hexane, ethyl acetate, n-butanol and water extracts of Polyporus umbellatus were tested by diuretic experiment of normal rats in metabolic cage. The n-hexane extract and n-butanol extract were prepared separately by the bioassay-guided approach. Three isolated compounds doses (5, 10 and 20 mg/kg BW) were orally administered to normal rats. Water excretion rate, pH and content of Na⁺, K⁺ and Cl⁻ were measured in the urine of saline-loaded rats.

Results

n-Hexane extract (P < 0.05), n-butanol extract (P < 0.05) and three isolated compounds (ergosta-4,6,8(14),22-tetraen-3-one, ergosterol and d-mannitol) displayed diuretic activity.

Conclusions

The ergosta-4,6,8(14),22-tetraen-3-one was the strongest diuretic constituent in the three compounds. Ergosterol and d-mannitol were found to be also responsible for duiretic effects in Polyporus umbellatus for the first time. Data show that 20 mg/kg dose of the ergosterol for urine out put became significantly higher than in the control rats, but the ratio of Na⁺/K⁺ almost unaltered in the three doses. The highest dose of the d-mannitol was significant and increased the cumulative urine output. Regarding the electrolyte excretion, data show that the doses 10 and 20 mg/kg produce significant increase for excretion of Na⁺ and Cl⁻. The present results provide a quantitative basis explaining application of Polyporus umbellatus as a diuretic medicine. The result proved that its diuretic effects were also due to the contribution of multi-components in clinical application.     

引种不同来源穿心莲叶中穿心莲内酯及脱水穿心莲内酯积累分析

目的观察不同来源穿心莲叶中穿心莲内酯和脱水穿心莲内酯的积累,以期为品种选育提供依据。方法收集同一引种地各生长阶段的不同来源地穿心莲叶,以HPLC测定叶中穿心莲内酯和脱水穿心莲内酯的含量。结果经数据分析,穿心莲内酯和脱水穿心莲内酯与生长期呈现明显的相关性。穿心莲内酯含量无论大叶型还是小叶型与始花期均成正相关,即开花期越晚,生长期越长,含量越高,大叶型相关系数的平均值为0.951,小叶型为0.899;脱水穿心莲内酯含量与始花期均成负相关,即开花期越晚,脱水穿心莲内酯含量越低,大叶型相关系数均值为-0.930,小叶型为-0.979。结论建议穿心莲品种应从大叶型中选育始花期晚的品种。     

海螵左金丸联合三联疗法治疗幽门螺杆菌感染随机平行对照研究

[目的]观察海螵左金丸联合三联疗法治疗幽门螺杆菌感染疗效。[方法]使用随机平行对照方法,将220例门诊患者按随机数字表法分为两组。对照组110例三联疗法,兰索拉唑,30mg／次,2次／d。克拉霉素,500mg／次,2次／d。阿莫西林,lg／次,2次／d。治疗组110例海螵左金丸（海螵蛸30g,黄连10g,吴茱萸5g;胃热或湿热加蒲公英15g,麸炒枳壳、胆南星、竹茹各10g,车前草、扁豆花各30g;胃热或胃阴不足加蒲公英15g,玉竹、生地、知母、竹茹、沙参各10g,扁豆花30g,山药20g;脾胃虚弱加党参20g,茯苓、陈皮、炒白术各10g,砂仁5g,薏苡仁、扁豆花各30g）。1剂／d,水煎120mL,早晚口服。西药治疗同对照组。连续治疗10d为1疗程。观测临床症状、14C-UBT检测、不良反应。治疗1疗程,判定疗效。[结果]治疗组痊愈76例,有效16例,无效18例,总有效率83．64％。对照组痊愈48例,有效27例,无效35例,总有效率68．18％。治疗组疗效优于对照组（P〈0．05）。[结论]海螵左金丸联合三联疗法治疗幽门螺杆菌感染效果显著,值得推广。     

MMP-2、MMP-14、TIMP-2在退变腰椎间盘髓核组织的表达及意义

目的探讨基质金属蛋白酶-2（MMP-2）、基质金属蛋白酶-14（MMP-14）和金属蛋白酶组织抑制剂-2（TIMP-2）在退变腰椎间盘髓核组织表达的意义。方法应用免疫组织化学法检测36例退变腰椎间盘髓核组织（退变组）、20例腰椎骨折腰椎间盘髓核组织（对照组）MMP-2、MMP-14和TIMP-2表达。结果退变组MMP-2、MMP-14表达明显高于对照组（P〈0.001）,TIMP-2表达无明显改变（P〉0.05）;椎间盘退变等级与MMP-2、MMP-14及TIMP-2表达呈正相关（分别rs=0.710,P〈0.001;rs=0.617,P〈0.001;rs=0.406,P=0.014）;MMP-2与MMP-14、TIMP-2表达呈正相关（分别rs=0.665,P〈0.001;rs=0.516,P=0.001）。结论 MMP-2、MMP-14和TIMP-2表达加强可能是导致椎间盘退变的重要原因之一。