ANTIBODY TO ONCOGENE PROTEIN PRODUCT AND ITS CONJUGATE WITH RICIN A-CHAIN

The proteins encoded by oncogene were thought to be tumor associated antigen. The protein P110 in MGC803, a human gastric cancer cell line, was purified as immunogen. The IgY to the gastric cancer was extracted from eggs laid by immunized hen. The IgY could react immunohistochemically with gastric cancers. Positive staining rates of PAF were 80% in gastric cancers and markedly higher than in cancers of other organs and normal gastric tissue. The IgY-Ricin A was synthesized by the IgY conjugated with Ricin A- chain. TCID50 of MGC803 treated by the IgY-Ricin A was 0. 01 mg/ml and markedly lower than other cell. These results showed the IgY-Ricin A were able to react with gastric cancers selectively.

Disorder structural predictions of the native EWS and its oncogenic fusion proteins in rapport with the function

The Intrinsic structural disorder (ISD) of native EWS and its fusion oncogenic proteins, including EWS/FliI, EWS/ATF1 and EWS/ZSG, was estimated by different Predictors. The ISD difference between the wild type and the oncogenic fusions found in the CTD is due to the fusion partner, usually a transcription factor (TF). A disordered region was found in the sequence (AA 132 - 156) of the NTD (EAD) of EWS, consisting of the longest region free of Y motifs. The IQ domain (AA 258 - 280), a Y-free region, flanked by two Y-boxes, is also disordered by all used Predictors. The EWS functional regions RGG1, RGG2 and RGG3 are predominantly disordered. A strong dependence was found between the structure of EWS protein and its oncogenic fusions, and their estimated ISD. The oncogenic function of the fusions is related to a decreased ISD in the CTD, due to the fused TF. The Predictors shown that the different isoforms have similar profiles, shifted with some amino acids, due to the translocations. On the bases of the prediction results, an analysis was made of the EWS sequence and its functional regions with increased ISD to make a relationship sequence-disorder-function that could be helpful in the design of antitumor agents against the corresponding malignances.

Effect of phosphorylation of MAPK and Stat3 and expression of c-fos and c-jun proteins on hepatocarcinogenesis and their clinical significance

AIM To study the effect of phosphorylation ofMAPK and Stat3 and the expression of c-fos andc-jun proteins on hepatocellular carcinogenesisand their clinical significance.METHODS SP immunohistochemistry was usedto detect the expression of p42/44MAPK, p-Stat3,c-fos and c-jun proteins in 55 hepatocellularcarcinomas (HCC) and their surrounding livertissues.RESULTS The positive rates and expressionlevels of p42/44MAPK, p-Stat3, c-fos and c-junproteins in HCCs were significantly higher thanthose in pericarcinomatous liver tissues (PCLT).A positive correlation was observed between theexpression of p42/44MAPK and c-fos proteins, andbetween p-Stat3 and c-jun, but there was nosignificant correlation between p42/44MAPK and p-Stat3 in HCCs and their surrounding livertissues.CONCLUSION The abnormalities of Ras/Rat/MAPK and JAKs/ Stat3 cascade reaction maycontribute to malignant transformation ofhepatocytes. Hepatocytes which are positive forp42/ 44MAPK, c-fos or c-jun proteins may bepotential malignant pre-cancerous cells.Activation of MAPK and Stat3 proteins may be anearly event in hepatocellular carcinogenesis.

Expressions of oncogenes c-fos and c-myc in skin lesion of cutaneous squamous cell carcinoma

Objective:To explore the expressions of c-fos and c-myc in skin lesion of cutaneous squamous cell carcinoma(CSCC).Methods:Using retrospective analysis.73 cases of CSCC were selected from Department of Dermatology,the Second Affiliated Hospital of Xi'an Jiaotong University.which were removed between January 2000 and January 2012.It was considered as experimental group.Meanwhile.11 cases of normal skin specimens of non tumor patients were selected as control group.The expression level of c-fos and c-myc was compared in the two groups.Results:The expressions of c-fos[72.60%(53/73)]and c-myc[83.56%(61/73)]in experimental group were statistically significant(P≤0.05)compared with control group(0%).Expression of c-myc protein was negatively related to differentiation of CSCC.The difference was statistically significant(X^2=7.26.P=0.001<0.05).While expression of c-fos protein was positively related to differentiation of CSCC.which was statistically significant(X^2=7.47,P=0.0012<0.025).Conclusions:The expression level of c-fos and c-myc can be used as an importan indicator of CSCC differentiation,and it has closely connection with the differentiated degree,which can guide clinical prognosis.

AU-rich element-binding proteins in colorectal cancer

Trans-acting factors controlling mRNA fate are critical for the post-transcriptional regulation of inflammation-related genes, as well as for oncogene and tumor suppressor expression in human cancers. Among them, a group of RNA-binding proteins called "Adenylate-Uridylate-rich elements binding proteins"(AUBPs)control mRNA stability or translation through their binding to AU-rich elements enriched in the 3'UTRs of inflammation-and cancer-associated mRNA transcripts. AUBPs play a central role in the recruitment of target mRNAs into small cytoplasmic foci called Processing-bodies and stress granules(also known as P-body/SG). Alterations in the expression and activities of AUBPs and Pbody/SG assembly have been observed to occur with colorectal cancer(CRC)progression, indicating the significant role AUBP-dependent post-transcriptional regulation plays in controlling gene expression during CRC tumorigenesis.Accordingly, these alterations contribute to the pathological expression of many early-response genes involved in prostaglandin biosynthesis and inflammation,along with key oncogenic pathways. In this review, we summarize the current role of these proteins in CRC development. CRC remains a major cause of cancer mortality worldwide and, therefore, targeting these AUBPs to restore efficient post-transcriptional regulation of gene expression may represent an appealing therapeutic strategy.

Function of apoptosis and expression of the proteins Bcl-2,p53 and C-myc in the development of gastric cancer

INTRODUCTIONIn China ,the incidence and mortality of gastric cancer rank the second among all cancers. Recent development of cancer [1-20].The aim of this study was investigat the insight of apoptosis and bcl-2, p53 and C-myc protein expression in the development of gastric cancer .

PDRG1 at the interface between intermediary metabolism and oncogenesis

PDRG1 is a small oncogenic protein of 133 residues. In normal human tissues, the p53 and DNA damageregulated gene 1(PDRG1) gene exhibits maximal expression in the testis and minimal levels in the liver. Increased expression has been detected in several tumor cells and in response to genotoxic stress. High-throughput studies identified the PDRG1 protein in a variety of macromolecular complexes involved in processes that are altered in cancer cells. For example, this oncogene has been found as part of the RNA polymerase Ⅱ complex, the splicing machinery and nutrient sensing machinery, although its role in these complexes remains unclear. More recently, the PDRG1 protein was found as an interaction target for the catalytic subunits of methionine adenosyltransferases. These enzymes synthesize S-adenosylmethionine, the methyl donor for, among others, epigenetic methylations that occur on the DNA and histones. In fact, downregulation of S-adenosylmethionine synthesis is the first functional effect directly ascribed to PDRG1. The existence of global DNA hypomethylation, together with increased PDRG1 expression, in many tumor cells highlights the importance of this interaction as one of the putative underlying causes for cell transformation. Here, we will review the accumulated knowledge on this oncogene, emphasizing the numerous aspects that remain to be explored.

Effects of Okadaic Acid, Retinoic Acid, and Phorbol Myristate Acetate Tumor Promoter on Oncogene Expression

The effect of okadaic acid (OA) on proto-oncogene protein expression of c-neu, c-myc, v-rasH, EGFR, and phosphotyrosine-containing phosphoproteins (P-Tyr) was investigated in rapidly growing (RG) normal human keratinocytes (NHK) and in SV-40 virally-transformed keratinocytes (SVK) cultured in a growth factor supplemented serum-free medium as assessed by indirect immunofluorescence microscopy. P-Tyr positively stains cell surface antigens (cytoplasm) diffusely at monopolar sites in RG NHK cultures. OA-treatment intensifies cytoplasmic P-Tyr staining at localized monopolar intercellular focal adhesion (IFA) sites with reduced cytoplasmic staining. P-Tyr expression was predominate at IFA sites with little cytoplasmic staining in RG SVK cultures. OA-treatment increased monopolar P-Tyr staining and cytoplasmic staining. OA-treatment in RG NHK cultures intensified cytoplasmic staining of c-myc and EGFR (epidermal growth factor receptor) expression. OA-treatment in RG NHK and SVK cultures intensified c-neu staining at monopolar IFA sites and intensified c-neu staining at both cytoplasmic and bipolar IFA sites in RG SVK cells. OA was especially cytotoxic for SVK cells. RA treatment decreased c-neu expression in RG NHK cultures while TPA treatment has a lesser effect on both cytoplasmic and IFA sites. RA treatment also decreased P-Tyr staining in both NHK and SVK cells. Again, TPA had a lesser inhibitory effect on P-Tyr staining pattern. RA-treatment had a similar effect on P-Tyr staining of RG cultures of a mouse fibroblast cell line. These results confirm the generality of OA, RA and TPA on the regulation of oncogene expression in both normal and malignantly transformed keratinocytes.

Downregulation of the Spi-1/PU.1 oncogene induces the expression of TRIM10/HERF1, a key factor required for terminal erythroid cell differentiation and survival

Spi-1/PU.1 和 Fli-1 oncoproteins 的持续表示在老鼠 erythroleukemia 房间堵住 globin 基因激活；然而，仅仅 Spi-1/PU.1 表示禁止 exon 的包括 16 在成熟 4.1R mRNA。这个拼接的事件为红血房间膜正直为功能的 4.1R 蛋白质并且，因此是关键的。这份报告证明 Spi-1/PU.1 downregulation 导致 TRIM10/hematopoietic 戒指手指 1 的激活(HERF1 ) ，分成三部分的主题(修剪) 的一个成员为 globin 基因抄写需要的 /RBCC 蛋白质家庭。另外，我们证明 TRIM10/HERF1 为 exon 拼接调整被要求 16 在迟了的 erythroid 区别期间。用可诱导的 overexpression 和 silencing 途径，我们发现了那：(1 ) TRIM10/HERF1 击倒在导致的 dimethylsulfoxide (DMSO ) 禁止拼接的血红素生产和 exon 和扳机房间 apoptosis 房间；(2 ) TRIM10/HERF1 upregulation 被要求，但是在它的自己上是不够的激活 exon 保留；(3 ) Fli-1 没在 TRIM10/HERF1 表示上有效果，而也导致 DMSO 的 downregulation 或 Spi-1/PU.1 shRNA 击倒表示是足够的激活 TRIM10/HERF1 表示；并且(4 ) Spi-1/PU.1 击倒的扳机抄写和拼接的事件独立于化学正式就职。总的来说，这些数据显示主要 Spi-1/PU.1 downregulation 通过至少二条小径，其一条要求 TRIM10/HERF1 upregulation 和平行对迟了的 erythroid 区别起作用 Spi-1/PU.1-induced Fli-1 用以遮闭之物规章的串联。

Polymerase chain reaction-single strand conformational polymorphism analysis of rearranged during transfection proto-oncogene in Chinese familial hirschsprung's disease

AIM: To investigate the relationship between mutations of rearranged during transfection (RET) proto-oncogene and Chinese patients with Hirschsprung's disease (HD), and to elucidate the genetic mechanism of familial HD patient at the molecular level.METHODS: Genomic DNA was extracted from venous blood of probands and their relatives in two genealogies.Polymerase chain reaction (PCR) products, which were amplified using specific primers (RET, exons 11, 13, 15and 17), were electrophoresed to analyze the single-strand conformational polymorphism (SSCP) patterns. The positive amplified products were sequenced. Forty-eight sporadic HD patients and 30 normal children were screened for mutations of RET proto-oncogene simultaneously.RESULTS: Three cases with HD in one family were found to have a G heterozygous insertion at nucleotide 18 974 in exon 13 of RET cDNA (18 974insG), which resulted in a frameshift mutation. In another family, a heterozygosity for T to G transition at nucleotide 18 888 in the same exon which resulted in a synonymous mutation of Leu at codon 745 was detected in the proband and his father. Eight RET mutations were confirmed in 48 sporadic HD patients.CONCLUSION: Mutations of RET proto-oncogene may play an important role in the pathogenesis of Chinese patients with HD. Detection of mutated RET proto-oncogene carriers may be used for genetic counseling of potential risk for HD in the affected families.

Qualitative and Quantitative Studies of Polygene Proteins Expression in Esophageal Precancerous Lesions and Esophageal Carcinoma

Objective： To examine the expressions of MDM2, P53 and P27 proteins in chronic esophagitis, para-cancer mucosa and esophageal carcinoma. Methods： Immunohistochemistry was used to detect the expressions of MDM2, P53 and P27 proteins in forty-seven patients suffering from chronic esophagitis and eighty-five cases of esophageal carcinoma and corresponding para-cancer mucosa. Flow cytometry（（FCM） was applied to detect the quantities of these proteins expressed in fresh tissues of 48 cases of esophageal cancer and their para-cancer tissues and 24 cases of relative normal mucosa at the surface of cutting edge. Results： Immunohistochemistry results showed that the expressions of the three studied proteins were very similar in the epithelia of chronic esophagitis and para-cancer mucosa （P〉0.05）. Both the qualitative and quantitative studies displayed that the P53 protein had no expression and its accumulations would appear only in the early stages of esophagus canceration while the MDM2 and P27 proteins had different degrees of expressions in cases of normal esophageal mucosa. MDM2 protein markedly increased in the advanced stages of esophageal canceration. A quantitative study showed that the expression of P27 protein had a linearity of decreasing tendency （F=9.132, P=0.002） in the course of esophageal canceration. Conclusion： Chronic esophagitis may be a precancerous lesion. Owing to the changes of the P53 and P27 proteins, we can also conclude that these occur in the early stages of esophagus oncogenesis, however the changes of MDM2 expression may occur in the advanced stage of esophageal canceration.

Eosinophil MBP Extract Modulates Oncogene Expression in Prostate Tumor Cells: A Preliminary Study with Monolayer Cultures

Prostate cancer is the second leading cause of cancer deaths in the United States and remains a significant health concern for men throughout the world. Despite the discovery of promising immunotherapeutic strategies, curative outcomes remain elusive. We have investigated eosinophils as potential anti-cancer effector cells, and have reported the ability of their toxic granular proteins (MBP, EPO, ECP, EDN) to inhibit prostate tumor cell growth?in vitro. This study investigates the effect of eosinophil MBP extract on the expression of oncogenes p53, bcl-xl, bax, and c-myc, which modulate tumor growth, proliferation, and apoptosis. Briefly, granular proteins were differentially extracted from GRC.014.22 and GRC.014.24, eosinophilic cell lines established in our laboratory from a patient with moderate asthma. Protein extracts were fractionated on Sephadex G-50 columns, and prostate tumor cell lines DU-145, LNCaP, PC-3, and HPC8L (established in our laboratory from a tumor resected from an African American patient) were treated with MBP extracts from the pooled third peaks. Colony formation and monolayer cell growth inhibition assays were used to evaluate the protein’s growth inhibitory activity against prostate tumor cells;and gene expression analyses, to determine p53, bcl-xl, bax, and c-myc oncogene expression. We show that the granular proteins were potent in their action on HPC8L, inhibiting colony formation in a dose-dependent manner. Treated prostate tumor cell lines trended toward apoptosis-induction, as evident in bcl-xl/bax ratios < 1, increased p53 expression, and up or downregulation of c-myc. These preliminary results demonstrate the growth inhibitory potential of eosinophil granular proteins and strongly support the hypothesis that eosinophils modulate the expression of oncogenes associated with prostate tumor proliferation and apoptosis. More importantly, this study offers insights into possible applications of eosinophilic mediators in oncogenic-targeted prostate cancer treatment strategies and demonstrates the potential therapeutic implications of enhancing eosinophilic activity in prostate cancer.

Targeting the“undruggable”cancer driver genes:Ras,myc,and tp53

The term“undruggable”is to describe molecules that are not targetable or at least hard to target pharmacologically.Unfortunately,some targets with potent oncogenic activity fall into this category,and currently little is known about how to solve this problem,which largely hampered drug research on human cancers.Ras,as one of the most common oncogenes,was previously considered“undruggable”,but in recent years,a few small molecules like Sotorasib(AMG-510)have emerged and proved their targeted anti-cancer effects.Further,myc,as one of the most studied oncogenes,and tp53,being the most common tumor suppressor genes,are both considered“undruggable”.Many attempts have been made to target these“undruggable”targets,but little progress has been made yet.This article summarizes the current progress of direct and indirect targeting approaches for ras,myc,two oncogenes,and tp53,a tumor suppressor gene.These are potential therapeutic targets but are considered“undruggable”.We conclude with some emerging research approaches like proteolysis targeting chimeras(PROTACs),cancer vaccines,and artificial intelligence(AI)-based drug discovery,which might provide new cues for cancer intervention.Therefore,this review sets out to clarify the current status of targeted anti-cancer drug research,and the insights gained from this review may be of assistance to learn from experience and find new ideas in developing new chemicals that directly target such“undruggable”molecules.

虎杖苷调节Akt/MDM2/p53信号通路对胆囊癌细胞增殖、迁移和细胞周期的影响

目的探讨虎杖苷(PD)调节蛋白激酶B/原癌基因MDM2/抑癌基因p53信号通路对胆囊癌细胞增殖、迁移和细胞周期的影响。方法以人胆囊癌细胞株(GBC-SD)为研究对象,体外培养人胆囊癌细胞株(GBC-SD),使用浓度为10~160 mmol/L的虎杖苷处理细胞24、48、72 h,采用CCK-8法检测细胞的增殖能力,确定最佳实验浓度。将GBC-SD细胞分为对照组(Control组)、虎杖苷低、中、高浓度组(PD-L组、PD-M组、PD-H组)、虎杖苷+Akt激活剂组(PD+SC79组),Transwell小室法评价细胞的迁移能力,Hoechst染色观察细胞的凋亡,流式细胞术检测细胞周期与细胞凋亡,Western blot检测Akt、MDM2、p53磷酸化水平,建立荷瘤小鼠模型评价虎杖苷对胆囊癌肿瘤生长的影响。结果浓度为10~160 mmol/L的虎杖苷处理细胞24 h,可显著抑制GBC-SD细胞的增殖活性,选择10、20、40 mmol/L的虎杖苷进行后续实验;与Control组比较,PD-L组、PD-M组、PD-H组GBC-SD细胞的迁移数、细胞凋亡率、G2/M期细胞比例及S期细胞比例、P-Akt、P-MDM2蛋白表达显著降低,G0/G1期细胞比例、P-p53蛋白表达显著升高,且呈浓度依赖性(P<0.05);与PD-H组比较,PD+SC79组GBC-SD细胞的迁移数、细胞凋亡率、G2/M期细胞比例及S期细胞比例、P-Akt、P-MDM2蛋白表达显著升高,G0/G1期细胞比例、P-p53蛋白表达显著降低(P<0.05);虎杖苷干预治疗后,小鼠移植瘤的生长速度显著降低(P<0.05)。结论虎杖苷可以通过调节Akt/MDM2/p53信号通路使细胞周期阻滞,抑制胆囊癌细胞增殖、迁移。

术前血清Lp-PLA2与NLRP3水平对IABP辅助PCI治疗的高危冠心病患者发生MACE的预测价值

【目的】探讨术前血清脂蛋白相关磷脂酶A2(Lp-PLA2)与核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)水平对主动脉内球囊反搏(IABP)辅助经皮冠状动脉介入治疗(PCI)高危冠心病患者发生心血管不良事件(MACE)的预测价值。【方法】选取本院收治的120例高危冠心病患者,所有患者均行IABP辅助PCI治疗。统计术后6个月内MACE发生情况,分为非MACE组和MACE组,比较两组术前血清Lp-PLA2、NLRP3水平,分析术前血清Lp-PLA2、NLRP3水平与冠脉狭窄程度的相关性,采用受试者工作特征(ROC)曲线分析术前血清Lp-PLA2、NLRP3水平预测术后发生MACE的价值。【结果】120例IABP辅助PCI术后高危冠心病患者MACE发生率为34.17%(41/120);MACE组术前血清Lp-PLA2、NLRP3水平均高于非MACE组(P<0.05)。Spearman相关性分析显示,术前血清Lp-PLA2、NLRP3水平与冠脉狭窄程度呈正相关(r s=0.750、0.815,均P<0.05)。重度患者术前血清Lp-PLA2、NLRP3水平高于中度、轻度患者,中度患者高于轻度患者(P<0.05)。ROC曲线分析显示,术前血清Lp-PLA2、NLRP3水平单独预测的曲线下面积分别为0.770、0.844,二者联合预测AUC为0.909(P<0.05)。【结论】术前血清Lp-PLA2、NLRP3水平与高危冠心病患者冠脉狭窄程度呈正相关,二者联合检测可为临床预测高危冠心病患者IABP辅助PCI手术治疗后发生MACE提供一定参考依据。

西藏地区结直肠癌免疫治疗和靶向治疗相关分子标志物的检测及意义

目的研究西藏地区结直肠癌中SWI/SNF相关、基质相关、肌动蛋白依赖性染色质调节因子A亚科成员4(SMARCA4)/Brahma相关基因1、V-raf鼠类肉瘤病毒癌基因同源物B(BRAF)、P53、程序性死亡受体1(PD-1)及程序性死亡配体1(PD-L1)免疫组织化学表达和BRAF、神经营养因子酪氨酸受体激酶(NTRK)基因改变情况,为西藏地区结直肠癌患者的靶向治疗及免疫治疗提供依据。方法收集2015年1月至2021年7月西藏自治区人民医院经手术切除病理确诊为结直肠癌病例64例,全部病例均进行SMARCA4、BRAF、P53、PD-1、PD-L1免疫组织化学染色和NTRK1、NTRK2、NTRK3融合基因荧光原位杂交检测及BRAF V600E基因突变PCR检测。结果64例结直肠癌病例男女比例1.21∶1,平均年龄(56.59±13.27)岁;46例(71.88%)位于结肠,18例(28.12%)位于直肠;60例(93.75%)为腺癌,4例(6.25%)为其他类型;11例(17.19%)为T1或T2期,53例(82.81%)为T3或T4期;24例(37.50%)出现淋巴结转移。免疫组织化学方面,64例中1例(1.56%)SMARCA4部分肿瘤细胞表达减弱或缺失,4例(6.25%)BRAF肿瘤细胞阳性表达,35例(54.69%)P53为突变型表达;45例(70.31%)PD-1肿瘤相关免疫细胞阳性比例分数<10%,19例(29.69%)≥10%;52例(81.25%)PD-L1联合阳性分数<10,12例(18.75%)≥10。64例NTRK1、NTRK2、NTRK3融合基因检测均为阴性;4例(6.25%)检测到BRAF V600E基因突变;1例SMARCA4表达缺失病例未检测到SMARCA4基因改变。PD-L1的表达与错配修复缺陷/高度微卫星不稳定和PD-1的高表达呈显著正相关(χ^(2)=10.223,P=0.001;χ^(2)=11.979,P=0.001)。结论西藏地区结直肠癌中较少出现SMARCA4表达减弱或缺失及NTRK融合基因改变,少数病例有BRAF V600E基因突变,Pan-TRK和BRAF免疫组织化学可作为NTRK融合基因及BRAF基因突变的初筛方法。错配修复缺陷/高度微卫星不稳定的病例中更容易出现PD-L1蛋白高表达,这部分患者有望获益于免疫治疗。P53突变与PD-L1表达无相关性,PD-1的高表达和PD-L1的高表达呈正相关。

无水奶油和BL-41的比例对淡奶油稳定性的影响

研究了无水奶油和BL-41两种油脂之间不同的比例对淡奶油粒径分布、界面蛋白含量、脂肪部分聚结率及表观粘度的影响,并在此基础上探讨了其作用机理。研究结果表明,随着BL-41比例的不断增大,淡奶油的上层粒径d3,2、脂肪部分聚结率和表观粘度呈先增大后减小的趋势,在无水奶油∶BL-41为17.5∶17.5时达到最大值,而界面蛋白含量则先降低后升高,在无水奶油∶BL-41为17.5∶17.5时达到最小值。此外,随着储存时间的延长,上层粒径d3,2、脂肪部分聚结率和表观粘度均逐渐增大,而界面蛋白含量则逐渐降低。

基于网络药理学和实验验证探讨加味小柴胡汤治疗咳嗽变异性哮喘的分子机制

目的通过网络药理学、分子对接和实验验证对加味小柴胡汤治疗咳嗽变异性哮喘的主要活性成分及潜在作用机制进行探讨。方法应用网络药理学预测加味小柴胡汤治疗咳嗽变异性哮喘可能的作用机制,并通过分子对接预测活性成分的结合位点。构建哮喘大鼠模型,将60只大鼠随机分为正常组、模型组、地塞米松片组[0.5 mg/(kg·d)]、加味小柴胡汤组[5 g/(kg·d)],每组15只。正常组、模型组给予生理盐水2 mL灌胃,每日灌胃2次。给药4周后取大鼠血清及肺组织,ELISA法检测血清白细胞介素-6(interleukin-6,IL-6)、白细胞介素-13(interleukin-13,IL-13)、免疫球蛋白E(immunoglobulin E,IgE)、干扰素-γ(interferon-γ,INF-γ)水平,Western blot法检测肺组织丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)、GATA结合蛋白-3(GATA-binding protein-3,GATA-3)表达水平。结果网络药理学共筛选出加味小柴胡汤有效成分1483种,作用靶点274个,咳嗽变异性哮喘相关靶点7509个,其交集靶点204个。GO和KEGG富集分析主要涉及信号转导、炎症反应、细胞凋亡等一系列的生物学反应过程,主要参与表皮生长因子受体(epidermal growth factor receptor,EGFR)、丝裂原活化蛋白激酶1(mitogen-activated protein kinase 1,MAPK1)、丝裂原活化蛋白激酶3(mitogen-activated protein kinase 3,MAPK3)、RELA癌基因(RELA proto-oncogene,RELA)、细胞肿瘤抗原p53(cellular tumor antigen P53,TP53)、细胞性骨髓细胞瘤病病毒癌(myelocytomatosis virus carcinoma,MYC)和蛋白激酶Cα(protein kinase Cα,PRKCA)等靶点的调控。分子对接结果表明,筛选得到的主要活性成分与靶点有较强的结合力。与正常组比较,模型组大鼠肺组织中IL-6、IL-13、IgE、MAPK、GATA-3升高(P<0.05),INF-γ降低(P<0.05)。与模型组比较,地塞米松片组及加味小柴胡汤组IL-6、IL-13、IgE、MAPK、GATA-3降低(P<0.05),INF-γ升高(P<0.05)。与地塞米松片组比较,加味小柴胡汤组大鼠IL-6、IL-13、IgE降低(P<0.05),INF-γ升高(P<0.05)。结论加味小柴胡汤对咳嗽变异性哮喘具有治疗作用,其作用机制可能与EGFR、MAPK1、MAPK3、RELA、TP53、MYC和PRKCA靶点有关。

血清GFAP、MMP-9检测对高血压脑出血患者神经功能损伤程度的预测价值

【目的】探讨高血压脑出血(HICH)患者胶质纤维酸性蛋白(GFAP)、基质金属蛋白酶-9(MMP-9)与神经功能损伤程度的关系。【方法】102例HICH患者和85例未发生脑出血的高血压患者,分别记为HICH组、高血压组,另选取80例体检健康者,设为健康组,比较三组GFAP、MMP-9水平。采用美国国立卫生研究院卒中量表(NIHSS)评估HICH患者神经功能损伤程度,并据此分为轻度组、中度组和重度组。对比不同神经功能缺损程度HICH患者的GFAP、MMP-9水平。采用Pearson相关性分析HICH患者GFAP、MMP-9水平与神经功能损伤程度的相关性。随访6个月,依据格拉斯哥预后评分(GOS)评估HICH患者预后情况,比较预后良好组和预后不良组患者GFAP、MMP-9水平。制作受试者工作特征(ROC)曲线,以曲线下面积(AUC)分析GFAP、MMP-9及两者联合对HICH患者预后的预测价值。【结果】高血压组和HICH组患者GFAP、MMP-9水平高于健康组(P<0.05);HICH组患者血清GFAP、MMP-9水平高于高血压组(P<0.05)。中度组和重度组患者GFAP、MMP-9水平高于轻度组(P<0.05);重度组患者GFAP、MMP-9水平高于中度组(P<0.05)。HICH患者GFAP、MMP-9与神经功能损伤程度呈正相关(P<0.05)。预后不良组GFAP、MMP-9水平高于预后良好组(P<0.05)。ROC曲线结果显示,GFAP、MMP-9及两者联合对HICH患者预后预测的AUC分别为0.978、0.884和0.925,GFAP对HICH患者预后的预测价值最高。【结论】血清GFAP、MMP-9水平与HICH患者神经功能损伤程度、预后有关,且对患者预后的预测效能较高。

血清CRP、RDW与NT-proBNP对不同严重程度慢性阻塞性肺疾病合并心力衰竭的预测价值

【目的】探讨血清C反应蛋白(CRP)、红细胞分布宽度(RDW)与脑利钠肽前体(NT-proBNP)对不同严重程度慢性阻塞性肺疾病合并心力衰竭的预测价值。【方法】选取西安交通大学第一附属医院榆林医院感染性疾病科和安康市中医医院呼吸与危重症医学科2019年10月至2020年12月收治的90例慢性阻塞性肺疾病患者,按照检查结果和临床症状将患者分为单纯慢性阻塞性肺疾病组(单纯组,n=50)和慢性阻塞性肺疾病合并心力衰竭组(合并组,n=40),另选取同期健康体检志愿者50例作为对照组,比较三组血清CRP、RDW与NT-proBNP水平。将40例慢性阻塞性肺疾病合并心力衰竭组患者根据美国纽约心脏病学会(NYHA)分级分为Ⅱ级、Ⅲ级、Ⅳ级,比较不同分级患者血清CRP、RDW与NT-proBNP水平;比较不同严重程度患者CRP、RDW与NT-proBNP水平及近期疗效,采用受试者工作特征(ROC)曲线分析CRP、RDW与NT-proBNP联合对慢性阻塞性肺疾病患者合并心力衰竭的预测价值。【结果】单纯组、合并组血清CRP、RDW与NT-proBNP水平均高于对照组,合并组血清CRP、RDW与NT-proBNP水平高于单纯组(P<0.05);Ⅳ级、Ⅲ级慢性阻塞性肺疾病合并心力衰竭患者血清CRP、RDW与NT-proBNP水平高于Ⅱ级,Ⅳ级血清CRP、RDW与NT-proBNP水平高于Ⅲ级(P<0.05);慢性阻塞性肺疾病急性加重期患者血清CRP、RDW与NT-proBNP水平高于稳定期(P<0.05);稳定期患者临床疗效率高于急性加重期患者(P<0.05),血清CRP、RDW与NT-proBNP联合预测慢性阻塞性肺疾病患者合并心力衰竭的敏感度、特异度均高于单项检测。【结论】慢性阻塞性肺疾病合并心力衰竭患者血清CRP、RDW与NT-proBNP水平异常升高,其水平与疾病严重程度和预后密切相关,三者联合检测对于判断患者病情具有重要意义。