The Effects of Tetrandrine (TT) and Polyvinylpyridine-N-Oxide (PVNO) on Gene Expression of Type Ⅰand Type ⅢCollagens during Experimental Silicosis

In the screening tests of drugs for silicosis in our laboratory, we found that TT, a type of alkaloid isolated from Stephania tetrandra, could inhibit the development of experimental silicosis of rats and the synthesis of collagen in rat lung. Chest X-rays of silicotic patients treaied with TT for 1-3 years showed obvious changes. The silicotic nodules became smallel and shadows became clearer. PVNO was proved to have anti-silicotic effect on animal and clinically. This presentation reports the effect of them on collagen mRNA.Dot blot results showed that 1 (Ⅰ) and 1 (Ⅲ) mRNA levels increased significantly at 60 and 120 days after the rats were exposed to silica dust. The mRNA levels went down at 1 and 3 months after treated by TT and PVNO. In situ hybridization observation revealed that the silver grains of Type Ⅰand Type Ⅲ collagen were scattered within the fibroblasts in cellular nodules and in thickened interstitium of silicosis tissue. The amounts of mRNA silver grains decreased in the lung tissue treated by TT and PVNO. It was suggested that TT and PVNO may inhibil the gene expression of collagen during silicosis

Expression of Porcine Interleukin-2 and Porcine Interleukin-6 and Their Adjuvant Effects on Gene Deleted Vaccine of Pseudorabies Virus(TK^-/gG^-/LacZ^+)

Porcine interleukin-2 and porcine interleukin-6 cDNA sequences were cloned into the expressing vectors pET-28a and pGEX-KG respectively. They were expressed in E. coli BL21(DE3)with high-level production. The gene deleted vaccine of pseudorabies virus Ea strain(TK-/gG-/LacZ+)was mixed with the two different purified recombinant proteins each, or both, with the doses of 2, 5 or 10 μg ml-1. Ten groups of pseudorabies negative antibody swines were immuned twice with tested vaccines with different doses, or control vaccine, respectively. The antibody liters of the test groups were detected by neutralization test, and the daily weight gains of swines were calculated and analyzed statistically. In the study, all the neutralizing antibody ti-ters in test groups were higher than the control group, and the recombinant proteins appeared a dose dependent adjuvant effect. The tested vaccines with 2 μg ml-1 pIL-2 and with 10 μg ml-1 pIL-2/pIL-6 got significant and extremely significant differences, compared with the vaccines without pILs. The difference of the daily weight gain indicated the potential positive influence of pIL-2 and pIL-6 on immune protection.

Genetic expression and effects of the rolled leaf gene Rl(t) in hybrid rice (Oryza sativa L.)

We constructed a nearisogenic line of rolled leaf gene Rl(t), which ex-pressed incompletely dondnance for the character of rolled leaf(RL), with ge-netic background of Zhenshan 97B. Using RL Zhenshan 97B and the originalZhenshan 97B as the female parents, and Minghui 63 and Yanhui 559 as themale parents, crosses of RL Shanyu 63 (RS63) and Shanyu 63(S63), RLShanyou 559 (RS559) and Shanyou 559 (S559) were made. Inheritance andeffects of Rl(t) in hybrid rice were studied at the flowering and at the 20 d afterflowering, respectively. Results were as follow:

Effects of Mycobacterium vaccae vaccine in a mouse model of tuberculosis: protective action and differentially expressed genes

Background:Tuberculosis is a leading cause of death worldwide.BCG is an effective vaccine,but not widely used in many parts of the world due to a variety of issues.Mycobacterium vaccae(M.vaccae)is another vaccine used in human subjects to prevent tuberculosis.In the current study,we investigated the potential mechanisms of M.vaccae vaccination by determining differentially expressed genes in mice infected with M.tuberculosis before and after M.vaccae vaccination.Methods:Three days after exposure to M.tuberculosis H37 Rv strain(5×10~5 CFU),adult BALB/c mice randomly received either M.vaccae vaccine(22.5μg)or vehicle via intramuscular injection(n=8).Booster immunization was conducted 14 and 28 days after the primary immunization.Differentially expressed genes were identified by microarray followed by standard bioinformatics analysis.Results:M.vaccae vaccination provided protection against M.tuberculosis infection(most prominent in the lungs).We identified 2,326 upregulated and 2,221 downregulated genes in vaccinated mice.These changes could be mapped to a total of 123 signaling pathways(68 upregulated and 55 downregulated).Further analysis pinpointed to the MyD88-dependent TLR signaling pathway and PI3 K-Akt signaling pathway as most likely to be functional.Conclusions:M.vaccae vaccine provided good protection in mice against M.tuberculosis infection,via a highly complex set of molecular changes.Our findings may provide clue to guide development of more effective vaccine against tuberculosis.

THE CLINICAL SIGNIFICANCE OF MULTIDRUG RESISTANCE GENE(mdr1) EXPRESSION IN ACUTE LEUKEMIA

Objective: To study the clinical significance of multidrug resistance gene expression in acute leukemia. Methods: The relationships between drug resistance of leukemia cells and prognosis, multidrug resistance gene (mdr1) were examined in 85 patients with acute leukemia and 20 normal controls by reverse transcriptase polymerase chain reaction (RTPCR). Results: The mdr1 positive rate in untreated group was 44.7%. The complete remission (CR) rate of mdr1 positive patients (23.9%) was significantly lower than that of mdr1 negative patients (88.5%) (P<0.005). The mdr1 expression level in relapsedrefractory group was higher than that of CR group. A gradually increased mdr1 mRNA level in CR patients indicated early relapse. Conclusion: The mdr1 positive rate in normal control and longterm survival patients was very low. The mdr1 expression was correlated with FrenchAmericanBritish Cooperative Group (FAB) classification. The mdr1 expression level was correlated with chemotherapeutic effect and prognosis. It is an unfavorable prognostic factor for patients with acute leukemia.

THE EFFECT OF db-cAMP ON THE GENE EXPRESSION OF CALMODULIN AND CYTOSKELETON IN THE TRANSFORMED CELLS

We have demonstrated that the distribution of microtubules (MT), mlcrofilaments (MF) and fibronectin (FN) were diminished, while the gene expression of the calmodulin and c- fos enhanced in the transformed C3H10T1/2 cells. After treatment with 1 mM db-cAMP for 1 hour and 2 hours, there was an early and repldly reduced in gene expression of Calmodulin and c-fos respectively. After db-cAMP treatment for 4 -5 days, the number of capping cells of ConA binding decreased significantly and the cell surface microvllll decreased as well. The growth of treated cells was inhibited markedly. By using 4F1 cDNA probe, which is preferentially expressed In G1 phase, we have found that the db- cAMP treated cells were accumulated at G1 phase. Of particular interest is the fact that the distribution of microtubules, mlcrofilaments and fibronectln were recovered after treatment with 1 mM db-cAMP for 6 days. It is suggested that the Inhibition of proliferation, alteration, of phenotype and reco- very of cytoskeleton is transformed cells after treatment with db-cAMP are related to the Inhibition of gene expression of Calmodulin.

Radioprotective effects of the expression of FLT3 ligand regulated by Egr-1 regulated element on radiation injury of SCID mice

Objective: In order to explore the radioprotective effects of the expression of hematopoietic growth factors regulated by radio-inducible promoter on radiation injury. Methods:The human FL (Flt3 ligand) cDNA and EGFP (enhanced green fluorescent protein) cDNA were linked together with IRES and then inserted into the eukaryotic expression vector pCI-Egr, which was constructed by substituting CMV promoter in pCIneo with the Egr-1 promoter (Egr-EF). The vector was transferred into human bone marrow stromal ...

Cloning and expression of human arresten gene and effect of its recombinant protein on endothelial cell proliferation

To clone human arresten gene and investigate biological activity of the recombinant protein.Methods Human arresten gene was obtained from the plasmid pGEMArr and subcloned into the BamHⅠ and Pst Ⅰ restriction sites of prokaryotic expression vector pRSET containing T7 promoter.The recombinant plasmid pRSETAN was subsequently transformed into the strain E.coli BL21(DE3),and the target gene was expressed under induction of IPTG.The expressed protein was extracted,purified by Ni 2+ chelation affinity chromatography and refoled.The effect of the recombinant protein on proliferation of human umbilical vein endothelial cells (HUVECs) was also analyzed with the MTT assay.Results Endonuclease digesting and DNA sequencing confirmed that the arresten gene was correctly inserted into the expression vector.The recombinant protein was hightly expressed in the form of inclusion body in the host bacteria after induction.SDS-PAGE analysis revealed that the recombinant protein with a molecular weight of 26×103 amounted to 27% of the total bacterial proteins.The purity of the expected protein could reach over 96% through affinity chromatography.After renaturation,the recombinant protein could reach over 96% through affinity chromatography.After renaturation,the recombinant protein could significantly suppress proliferation of human umbilical vein endothelia cells(HUVECs) induced by vascular endothelial growth factor(VEGF).Conclusion Human arresten gene was successfully cloned into the expression vector pRSET and expressed at high level in Escherichia coli.Purified and refolded arresten protein could effectively inhibit proliferation of vascular endothelia cells.2 refs.

EFFECT OF RADIX SALVIAE MILTIORRHIZAE ON THE GENE EXPRESSION OF NITRIC OXIDE SYNTHASE IN ISCHEMIC RAT BRAINS

The effect of Radix Salviae Miltiorrhizae (RSM) on the gene expression of nitric oxide synthase (NOS) in rat brains daring ischemia was studied with in situ hybridization and the results were analyzed with IBAS 2000 Image Analysis System. It was found that NOS gene expression of cerebral cortex and caudate-putamen was markedly increased in 24 hours in ischemia group (P【 0.01). In RSM-treated rats, although the NOS gene expression of ischemic side was also increased as compared with contralateral cortex and caudate-putamen, it was significantly lower in RSM-treated rats than those of the controls (P【 0.05, P【 0.01). The present study indicates that RSM can partly inhibit NOS gene ex pression of cerebral cortex and caudate-putamen during ischemia. This may be one of the protective mechanisms of RSM on cerebral ischemia.

Bioinformatics screening of breast cancer-related genes and potential drug research

Objective:To search the the differentially expressed genes between breast cell carcinoma tissues and normal tissues by using bioinformatics technology,and the potential therapeutic drugs for breast cancer were identified,which can provide reference for clinical immune targeted therapy and drug therapy of breast cancer in the future.Methods:"Breast cancer"was searched by using Gene Expression Omnibus(GEO),and GSE79586 chip data was downloaded.The differentially expressed genes in the control group and the breast cancer model group were screened by using bio-communication technology and subjected to GO function analysis,KEGG pathway analysis,differential gene characteristic expression analysis and protein-protein interaction network(PPI)analysis,and the analysis results were further visualized.Prognosis analysis,related function prediction and immune infiltration analysis were performed using the GEPIA,GeneMANIA,and Timer2.0 databases,respectively.Finally,the compounds with potential therapeutic effects on breast cancer are identified through Connectivity Map(CMap).Western blotting and real-time PCR(RT-PCR)were used to verify the core genes and potential therapeutic agents with the highest correlation in vitro.Results:A total of 3916 differentially expressed genes including 1786 up-regulated genes and 2130 down-regulated genes were screened.GO analysis showed that the differential genes were mainly involved in the positive regulation of phosphorylation,secretory vesicles,racemase and epimerase activities.KEGG analysis showed that differential genes were involved in systemic lupus erythematosus,alcoholism,sticky spots,amoebic dysentery Ras signal pathways and other disease pathways.The characteristic expression analysis of differential genes showed that MEK inhibitors,HSP90 inhibitors and signal transduction pathway kinase inhibitors were drugs similar to the differential genes.PPI results showed that H2AFJ,TFF1,GATA3,FOXA1,and CDH1 were core genes related to breast cancer.Two core genes of H2AFJ and TFF1 with the highest correlation were further selected for GEPIA analysis.The results of the analysis showed that the mRNA expression levels of H2AFJ and TFF1 in breast cancer cells were significantly higher than those in normal tissues,and there was a significant correlation with the pathological staging,overall survival rate and disease-free survival rate of breast cancer patients.H2AFJ and TFF1 may be potential prognostic biomarkers for survival of breast cancer patients.The functions of differentially expressed H2AFJ and TFF1 are mainly related to hormone receptor binding,epithelial structure maintenance and epigenetic negative regulation of genes,chromatin tissue involved in negative regulation of transcription,etc.The results of immune infiltration showed that the expressions of H2AFJ and TFF1 had a significant correlation with the infiltration of macrophages,neutrophils,monocytes,CD4+T,CD8+T,B lymphocytes and other immune cells.CMap results showed that compounds such as Gefitinib,Alpelisib,Sorafenib,and Sunitinib had potential therapeutic effects on breast cancer.Western blot and RT-PCR results showed that H2AFJ and TFF1 were significantly overexpressed in breast cancer cells.Gefitinib significantly inhibited the expression of H2AFJ and TFF1 in breast cancer cells(P<0.05,P<0.01).Conclusion:In this study,differentially expressed genes between breast cell carcinoma tissues and normal tissues were screened out by bioinformatics means to further identify key genes and compounds with potential therapeutic effects in the onset process of breast cancer and to further verify the effectiveness of the screened drugs on breast cancer through experiments.It will provide reference for clinical research and development of new drugs against breast cancer in the future in order to develop more effective treatment options.

Interaction mechanism of egg white-derived ACE inhibitory peptide TNGIIR with ACE and its effect on the expression of ACE and AT1 receptor

The egg white-derived hexapeptide TNGIIR inhibits angiotensin-converting enzyme(ACE)activity in vitro.In this work,molecular docking revealed that TNGIIR established hydrogen bonds with the S1(Ala 354),S2(Gln 281,His 513,Tyr 520 and Lys 511)and S1(Glu 162)pockets of ACE.In addition,the potential antihypertensive effect of the oral administration of TNGIIR in spontaneously hypertensive rats(SHR)was investigated,as was the effect of this peptide on the mRNA expression of ACE and angiotensin type 1(AT1)and type 2(AT2)receptors in renal tissue.The oral administration of TNGIIR(2,10 and 50 mg/kg)for up to four weeks did not reduce the blood pressure of SHR,in contrast to captopril(10 mg/kg,orally),but attenuated the mRNA expression of ACE and AT1 receptor(as did captopril).In contrast,both TNGIIR and captopril enhanced the expression of AT2 receptor mRNA.There was no change in the circulating concentration of angiotensin I,but a slight decrease(about 10%)was seen in the concentration of circulating angiotensin II with TNGIIR and captopril.

Stable Expression of Hantavirus H8205 Strain G1/IL-2 Gene and Immune Protection of the Fusion Gene

To explore the feasibility of stable expression of Hantavirus H8205 strain G1 segment and human IL-2 fusion gene in Vero cells, and to examine the immune protection effects on mice vaccinated with this recombinant eukaryotic expression vector containing Hantavirus G1 gene and IL-2 gene. With the help of lipofectamine, the Vero cells were transfected with pcDNA3.1/HisB-IL-2-G1 and the positive cells were selected by G418. IFAT and SDS-PAGE elec- trophoresis were used to determine the stable transfection and expression of recombinant protein. Each mouse was inoculated with plasmids intramuscularly （i.m.） three times, 2 boosts were given at 2-week intervals, serum anti-hantavirus antibodies were detected by ELISA and neutralizing antibodies （NAb） were detected by Plaque Reduction Neutralization Test. The fusion protein expressed in Vero cells was 78 kD, corresponding to the estimated molecular size. The neutralizing antibody titers of mice with pcDNA3.1/HisB-IL-2-G1 were 1：20-1：80. IL-2/G1 fusion gene could be transferred in Vero cells and stably express the fusion protein. Specific humeral immune responses in mice can be induced with the recombinant eukaryotic expression vector containing the fusion gene, which lays the foundation for further development of therapeutic HTNV vaccine.

CONGENITAL EXPRESSION OF mdr-1 GENE IN FRESH CANCER TISSUES FROM SEVERAL HIGH-INCIDENCE NEOPLASMS WITHOUT PREOPERATIVE CHEMOTHERAPY

Objective: The purpose of the present study is to detect characteristics of primary expression of mdr 1 gene in several neoplasms which has high morbidity in clinic. Methods: 151 resected samples, which are pathologically malignant and clinically untreated before operation, were obtained from Anyang Cancer Hospital. All of them were investigated with RT PCR for the expression of mdr 1 gene and correlated each other. Besides, we evaluated the advantages of RT PCR in this study. Results: The mdr 1 gene expression rate of these 151 samples, including cancers of stomach and gastric cardia (n=51), esophagus (n=46), colorectum (n=16), breast (n=15), thyroid (n=10), lung (n=9), uterine cervix (n=4), was 33.3%, 37%, 31.3%, 13.2%, 40%, 55%, 0%, respectively. Conclusion: Compared with other methods, RT PCR for studying mdr 1 gene expression had certain advantages in simplicity, reliability, and accuracy. Overexpression of mdr 1 gene in these neoplasms suggested that cases should be distinguished before treatment according to MDR of tumor and to choose effective drugs for individual cancer patient.

Biological effect of expression of exogenous human nuclear receptor hLRH-1 in SW480 cells and its molecular mechanism

Objective: To explore the possible biological function of human nuclear receptor hLRH-1 in tumorigenesis and progress of colon cancer. Methods: Plasmids pcDNA3-hLRH-1 were introduced into SW480 cells via lipofectamine. The expression of mRNA and protein of exogenous hLRH-1 were detected by RT-PCR and western blotting, respectively. MTT assay was carried out to survey the proliferation of SW480 cells with overexpression of hLRH-1. Meanwhile, the expression of proliferation-related genes cyclin E1 and cyclin D1, and apoptosis-related genes PTEN and Rb1, were analyzed by real- time RT-PCR. Results: The proliferation of SW480 cells was promoted under the condition of overexpression of hLRH-1. The expression of cyclin E1 was up-regulated significantly, while that of PTEN and Rb1 were down-regulated in SW480 cells with overexpressed hLRH-1. Conclusion: The expression of exogenous hLRH-1 in SW480 cells induced the proliferation resulting form up-regulation of cyclin E1, as well as participated in the regulation of apoptosis via influencing the expression of PTEN and Rb1.

The effect of adenovirus expressing wild-type p53 on 5-fluorouracil chemosensitivity is related to p53 status in pancreatic cancer cell lines

AIM: There are conflicting data about p53 function on cellular sensitivity to the cytotoxic action of 5-fluorouracil (5-FU).Therefore the objective of this study was to determine the combined effects of adenovirus-mediated wild-type (wt) p53 gene transfer and 5-FU chemotherapy on pancreatic cancer cells with different p53 gene status.METHODS: Human pancreatic cancer cell lines Capan-1^p53mut,Capan-2^p53wt, FAMPAC^p53mut, PANG1^p53mut, and rat pancreatic cancer cell lines AS^p53wt and DSL6A^p53null were used for in vitro studies. Following infection with different ratios of Adp53-particles (MOI) in combination with 5-FU, proliferation of tumor cells and apoptosis were quantified by cell proliferation assay (WST-1) and FACS (PI-staining). In addition, DSL6A syngeneic pancreatic tumor cells were inoculated subcutaneously in to Lewis rats for in vivostudies.Tumor size, apoptosis (TUNEL) and survival were determined.RESULTS: Ad-p53 gene transfer combined with 5-FU significantly inhibited tumor cell proliferation and substantially enhanced apoptosis in all four cell lines with an alteration in the p53 gene compared to those two cell lines containing wt-p53. In vivo experiments showed the most effective tumor regression in animals treated with Ad-p53 plus 5-FU. Both in vitroand in vivoanalyses revealed that a sublethal dose of Ad-p53 augmented the apoptotic response induced by 5-FU.CONCLUSION: Our results suggest that Ad-p53 may synergistically enhance 5-FU-chemosensitivity most strikingly in pancreatic cancer cells lacking p53 function. These findings illustrate that the anticancer efficacy of this combination treatment is dependent on the p53 gene status of the target tumor cells.

Adeno-associated virus mediated endostatin gene therapy in combination with topoisomerase inhibitor effectively controls liver tumor in mouse model

rAAV mediated endostatin gene therapy has beenexamined as a new method for treating cancer. However,a sustained and high protein delivery is required to achievethe desired therapeutic effects. We evaluated the impactof topoisomerase inhibitors in rAAV delivered endostatingene therapy in a liver tumor model.

Research on immune effect of two gene vaccines containing brZPC′and brLDHC_4′when in combined inoculation

ZPC and LDHC_4 play a key role in the process of recognition between sperm and egg or sperm movement,respectively.In this study,partial cDNA sequences of ZPC and LDH-C_4 of Microtus branditi(brZPC and brLDHC_4,respectively) were cloned by RT-PCR,and directly inserted into pCR3.1 vector to construct two gene vaccines(pCR3.1-brZPC' and pCR3.1-brLDHC'_4).pCR3.1-brZPC' and pCR3.1-brLDHC,' could express corresponding proteins in transiently transfected CHO cells.The adult female BALB/c mice were inoculated with the recombinant vaccine alone on in combination.The immunized mouse can produce specific antibody that recognizes the corresponding recombinant protein expressed by BL21 in vitro.Moreover,antibodies produced by combinedly immunized mouse were specific and direct,with no inhibitory effect between two vaccines observed when in combined inoculation.The test of cytokines indicated that the expression of IFNγin pCR3.1-brZPC'- and combinedly inoculated mouse increased obviously and the expression of IL2 in pCR3.l-brLDHC'_4- and combinedly inoculated mouse increased obviously,while the expression of IL4 in pCR3.1-brZPC,pCR3.l-brLDHC'_4 and combinedly inoculated group increased obviously.It was suggested that the combined inoculation with pCR3.1-brZPC' and pCR3.l-brLDHC'_4 could induce both humoral immune response and CTL response.In some sense,the combined inoculation may achieve a better contraceptive effect.The results also showed that,when used alone or in combination,these two recombinant vaccines did not do much harm to the follicular development of immunized mouse.So the combined inoculation with these two recombinant vaccines could be a better way to immunocontraception.This study may provide a theoretical basis for the following tests on antifertility in vivo.

基于药物基因组学探讨抗精神病药对首发精神分裂症疗效及不良反应的影响

目的:依据药物基因组学结果,探讨抗精神病药对首发精神分裂症患者疗效和药物不良反应的影响。方法:纳入2020年1月至2022年6月淮安市第三人民医院的首发精神分裂症患者,分为研究组和对照组各100例,研究组根据基因检测结果指导用药,对照组依据医师经验用药,分别于治疗前、治疗后4、8、12、16周使用阳性和阴性症状量表(positive and negative syndrome scale,PANSS)、临床疗效总评量表(clinical global impression,CGI)评定疗效,威斯康星卡片分类测验(Wisconsin card classification tests,WCST)及个人和社会功能评估量表(personal and social function assessment scales,PSP)评定认知及社会功能,并在治疗前后和两组之间比较,同时评定药物副反应量表(treatment emergent symptom scale,TESS)及作实验室检查,了解药物不良反应。结果:两组患者治疗后的PANSS总分、CGI、TESS、PSP、WCST等评分均较治疗前显著改善(P<0.05或P<0.001),研究组患者明显好于对照组(P<0.05或P<0.001),治疗后12~16周肝功能损害也轻于对照组,差异均有统计学意义(P<0.05或P<0.001)。血常规等实验室结果两组间差异无统计学意义(P>0.05)。结论:应用基因检测可提高精神分裂症患者药物治疗临床效果,减少不良反应的发生,指导临床合理、精准用药和个体化治疗。

药物基因检测对难治性精神分裂症患者治疗预后的影响

目的探讨药物基因组学检测结果应用对难治性精神分裂症患者疗效及药物不良反应的影响。方法选取2020年1月-2022年6月江苏省淮安市第三人民医院收治的100例难治性精神分裂症患者。依据基因检测结果指导用药,分别于治疗前、治疗4、8、12、16周使用阳性阴性症状量表(positive and egative symptom scale,PANSS)、临床疗效总评量表(clinical global impression,CGI)评定临床疗效,威斯康星卡片分类测验及个人和社会功能评估量表(personal and social function assessment scales,PSP)分别评定认知及社会功能改善情况,同时使用药物副反应量表(treatment emergent symptom scale,TESS)及做血常规、肝功能、肾功能和心电图等检查,以了解药物不良反应。结果治疗4周PANSS评分为(59.62±6.29)分,治疗8周PANSS评分为(54.83±7.37)分,治疗12周PANSS评分为(49.34±7.93)分,治疗16周PANSS评分(44.68±8.73)分,均低于治疗前的(62.93±5.55)分(P<0.001);治疗4、8、12和16周的CGI、PSP、威斯康星卡片分类测验等评分均优于治疗前(P<0.001)。治疗16周TESS评定与治疗4周比较,差异有统计学意义(P<0.01),但血常规、心电图、脑电图、肝功能和肾功能检查异常与否与治疗前比较,差异无统计学意义(P>0.05)。结论应用基因检测可显著提高难治性精神分裂症患者的临床疗效,且并不增加不良反应,因此基因检测可促进该病的临床合理用药、精准用药和个体化治疗。

Clustering Gene Expression Data Based on Predicted Differential Effects of GV Interaction

Microarray has become a popular biotechnology in biological and medical research. However, systematic and stochastic variabilities in microarray data are expected and unavoidable, resulting in the problem that the raw measurements have inherent “noise” within microarray experiments. Currently, logarithmic ratios are usually analyzed by various clustering methods directly, which may introduce bias interpretation in identifying groups of genes or samples. In this paper, a statistical method based on mixed model approaches was proposed for microarray data cluster analysis. The underlying rationale of this method is to partition the observed total gene expression level into various variations caused by different factors using an ANOVA model, and to predict the differential effects of GV （gene by variety） interaction using the adjusted unbiased prediction （AUP） method. The predicted GV interaction effects can then be used as the inputs of cluster analysis. We illustrated the application of our method with a gene expression dataset and elucidated the utility of our approach using an external validation.