Pharmacotranscriptomic profiles, which capture drug-induced changes in gene expression, offer vast potential for computational drug discovery and are widely used in modern medicine. However, current computational approaches neglected the associations within gene‒gene functional networks and unrevealed the systematic relationship between drug efficacy and the reversal effect. Here, we developed a new genome-scale functional module (GSFM) transformation framework to quantitatively evaluate drug efficacy for in silico drug discovery. GSFM employs four biologically interpretable quantifiers: GSFM_Up, GSFM_Down, GSFM_ssGSEA, and GSFM_TF to comprehensively evaluate the multi-dimension activities of each functional module (FM) at gene-level, pathway-level, and transcriptional regulatory network-level. Through a data transformation strategy, GSFM effectively converts noisy and potentially unreliable gene expression data into a more dependable FM active matrix, significantly outperforming other methods in terms of both robustness and accuracy. Besides, we found a positive correlation between RS_GSFM and drug efficacy, suggesting that RS_GSFM could serve as representative measure of drug efficacy. Furthermore, we identified WYE-354, perhexiline, and NTNCB as candidate therapeutic agents for the treatment of breast-invasive carcinoma, lung adenocarcinoma, and castration-resistant prostate cancer, respectively. The results from in vitro and in vivo experiments have validated that all identified compounds exhibit potent anti-tumor effects, providing proof-of-concept for our computational approach.

Objective To explore the effect of different post-processing methods of total spinal CT angiography(CTA)for displaying spinal dural arteriovenous fistula(SDAVF).Methods Total spinal CTA data of 55 patients with SDAVF were retrospectively analyzed.Traditional post-processing of original CTA images(modified tissue growth boneless volume rendering[VR]and full-range axial maximum intensity projection[MIP])were performed,while the axial,sagittal and coronal MIP reconstructions,axial,sagittal and coronal VR reconstructions,as well as axial,sagittal and coronal MIP+VR reconstructions of original CTA images on lesion layers were completed,respectively.Taken digital subtraction angiography(DSA)as the gold standards,a 5-point scale was used to subjectively evaluate the effect of displaying the location,the range and feeding artery of fistula shown on CTA images based on different post-processing methods.Results No significant difference of subjective score of location nor feeding artery of fistula was found among axial MIP,VR and MIP+VR images(all P＞0.05),which were all higher than that of CTA images reconstructed using other post-processing methods(all P＜0.05).Meanwhile,no significant difference of subjective scores of the range of SDAVF was detected among sagittal MIP,VR and MIP+VR images(all P＞0.05),which were all higher than that of CTA images obtained using other post-processing methods(all P＜0.05).Conclusion The location and feeding artery of SDAVF could be observed based on axial MIP,VR and MIP+VR reconstructions of the total spinal CTA,while sagittal MIP,VR and MIP+VR reconstructions were conducive to display the range of SDAVF.Combination of multiple post-processing methods was helpful for comprehensive understanding the composition and range of SDAVF.

AIM:To investigate the association between single nucleotide polymorphisms(SNPs)in the silent information regulator 1(SIRT1)gene and breast cancer risk in the Han Chinese population.METHODS:A total of 105 Han Chinese patients with breast cancer and 90 healthy controls were enrolled.Sequenom MassARRAY was used to detect the genotypes of SIRT1 gene loci,rs3740051,rs3758391,rs12778366 and rs2394443.The Hardy-Weinberg equilibrium(HWE)was analysed using the chi-square test.Multivariate logistic regression was employed to analyze the correlation be-tween each SNP and breast cancer susceptibility,as well as the relationship between the rs3758391 genotype and the clini-copathological characteristics of breast cancer in Han Chinese women.SHEsis software was used to assess linkage disequi-librium and haplotypes of the selected SNPs.The impact of genotypes at rs3758391 locus on SIRT1 protein expression was examined using Western blot.An additional 150 Han Chinese women with breast cancer and 150 healthy controls were en-rolled,and SIRT1 protein expression was assessed using immunohistochemistry.Logistic regression was performed to as-sess the relationship between high and low SIRT1 expression and the clinical characteristics of breast cancer.Kaplan-Mei-er website was used to determine the association between SIRT1 expression and patient prognosis.RESULTS:All four SNP loci conformed to the HWE test(P>0.05).The TC/TC+CC genotype of the SIRT1 rs3758391 locus significantly re-duced the risk of breast cancer compared with the TT genotype(TT vs TC:ORadj=0.348,95%CI:0.157～0.773,Padj=0.010;TT vs TC+CC:ORadj=0.381,95%CI:0.179～0.811,Padj=0.012),and correlated with earlier disease course(stage I/II),smaller tumor volume,and higher SIRT1 protein expression levels(P<0.05).SIRT1 expression was signifi-cantly lower in breast cancer tissues,and low SIRT1 expression was associated with larger tumor size,lymph node metasta-sis,and reduced recurrence-free survival(P<0.05).CONCLUSION:The TC/TC+CC genotype of the SIRT1 rs3758391 locus may be a protective factor for breast cancer in Han Chinese women,potentially reducing the risk of breast cancer and delaying disease progression by regulating SIRT1 expression.In addition,SIRT1 expression level is closely related to the clinical characteristics and prognosis of breast cancer.

AIM:To investigate the association between single nucleotide polymorphisms(SNPs)in the silent information regulator 1(SIRT1)gene and breast cancer risk in the Han Chinese population.METHODS:A total of 105 Han Chinese patients with breast cancer and 90 healthy controls were enrolled.Sequenom MassARRAY was used to detect the genotypes of SIRT1 gene loci,rs3740051,rs3758391,rs12778366 and rs2394443.The Hardy-Weinberg equilibrium(HWE)was analysed using the chi-square test.Multivariate logistic regression was employed to analyze the correlation be-tween each SNP and breast cancer susceptibility,as well as the relationship between the rs3758391 genotype and the clini-copathological characteristics of breast cancer in Han Chinese women.SHEsis software was used to assess linkage disequi-librium and haplotypes of the selected SNPs.The impact of genotypes at rs3758391 locus on SIRT1 protein expression was examined using Western blot.An additional 150 Han Chinese women with breast cancer and 150 healthy controls were en-rolled,and SIRT1 protein expression was assessed using immunohistochemistry.Logistic regression was performed to as-sess the relationship between high and low SIRT1 expression and the clinical characteristics of breast cancer.Kaplan-Mei-er website was used to determine the association between SIRT1 expression and patient prognosis.RESULTS:All four SNP loci conformed to the HWE test(P>0.05).The TC/TC+CC genotype of the SIRT1 rs3758391 locus significantly re-duced the risk of breast cancer compared with the TT genotype(TT vs TC:ORadj=0.348,95%CI:0.157～0.773,Padj=0.010;TT vs TC+CC:ORadj=0.381,95%CI:0.179～0.811,Padj=0.012),and correlated with earlier disease course(stage I/II),smaller tumor volume,and higher SIRT1 protein expression levels(P<0.05).SIRT1 expression was signifi-cantly lower in breast cancer tissues,and low SIRT1 expression was associated with larger tumor size,lymph node metasta-sis,and reduced recurrence-free survival(P<0.05).CONCLUSION:The TC/TC+CC genotype of the SIRT1 rs3758391 locus may be a protective factor for breast cancer in Han Chinese women,potentially reducing the risk of breast cancer and delaying disease progression by regulating SIRT1 expression.In addition,SIRT1 expression level is closely related to the clinical characteristics and prognosis of breast cancer.

Objective To explore the effect of different post-processing methods of total spinal CT angiography(CTA)for displaying spinal dural arteriovenous fistula(SDAVF).Methods Total spinal CTA data of 55 patients with SDAVF were retrospectively analyzed.Traditional post-processing of original CTA images(modified tissue growth boneless volume rendering[VR]and full-range axial maximum intensity projection[MIP])were performed,while the axial,sagittal and coronal MIP reconstructions,axial,sagittal and coronal VR reconstructions,as well as axial,sagittal and coronal MIP+VR reconstructions of original CTA images on lesion layers were completed,respectively.Taken digital subtraction angiography(DSA)as the gold standards,a 5-point scale was used to subjectively evaluate the effect of displaying the location,the range and feeding artery of fistula shown on CTA images based on different post-processing methods.Results No significant difference of subjective score of location nor feeding artery of fistula was found among axial MIP,VR and MIP+VR images(all P＞0.05),which were all higher than that of CTA images reconstructed using other post-processing methods(all P＜0.05).Meanwhile,no significant difference of subjective scores of the range of SDAVF was detected among sagittal MIP,VR and MIP+VR images(all P＞0.05),which were all higher than that of CTA images obtained using other post-processing methods(all P＜0.05).Conclusion The location and feeding artery of SDAVF could be observed based on axial MIP,VR and MIP+VR reconstructions of the total spinal CTA,while sagittal MIP,VR and MIP+VR reconstructions were conducive to display the range of SDAVF.Combination of multiple post-processing methods was helpful for comprehensive understanding the composition and range of SDAVF.

Objective:To explore the clinical characteristics and risk factors of abnormal urinary albumin/creatinine ratio(UACR) in obese population.Methods:Baseline data from 2011 to 2012 in Henan Sub-center of"Risk Evaluation of cAncers in Chinese diabeTic Individuals: A lONgitudinal(REACTION) study"were utilized and those of body mass index≥28 kg/m 2 were screened. The patients were divided into UACR normal group and UACR abnormal group(101 pairs) upon being matched on a 1∶1 basis by age and gender. Multivariate logistic regression analysis, receiver operating characteristic(ROC) curve, and restricted cubic spline(RCS)analysis were performed to explore the risk factors for abnormal UACR. Results:Compared with the normal UACR group, the UACR abnormal group had a higher number of alcohol consumers, a higher prevalence of hypertension, elevated systolic blood pressure, and triglyceride(all P<0.05). Multivariate logistic regression analysis showed that alcohol consumption( P=0.008), systolic blood pressure( P<0.001), triglyceride( P=0.049), and homeostasis model assessment for insulin resistance(HOMA-IR, P=0.033) were independent risk factors for abnormal UACR in obese people. The ROC curve analysis indicated that systolic blood pressure had the strongest diagnostic performance as a single factor(ROC curve area=0.801), and there was no significant difference in diagnostic performance compared to multiple factors combination. RCS analysis results showed that the probability of abnormal UACR increased monotonically with the increase of systolic blood pressure when the systolic blood pressure was between 130 and 158 mmHg(1 mmHg=0.133 kPa). When systolic blood pressure was not in the interval, the probability of abnormal UACR did not change significantly. The results of regression analysis of triglyceride subgroup showed that when triglyceride level was greater than or equal to 5.6 mmol/L, the risk of abnormal UACR level was significantly increased( P=0.029). Conclusion:Systolic blood pressure, triglyceride, HOMA-IR, and alcohol drinking history are independent risk factors for abnormal UACR in obese people. When systolic blood pressure is≥130 mmHg or triglyceride is≥5.6 mmol/L, the risk of abnormal UACR is significantly increased.

"Chinese model" of organ donation and transplantation in China has won acclaims from all over the world. Current contradictions between unbalanced and inadequate development of organ donation and transplantation and surging public demands for transplant services remain serious. And an acute shortage of donated organs is still the greatest difficulty. Improving organ donation rate per million population (PMP) and organ utilization rate has been a great challenge for organ donation teams in China. This review summarized the relevant experiences of Second Affiliated Hospital of Guangxi Medical University in fostering organ donation culture atmosphere and connotation to accelerate the high-quality development of organ donation. It was intended to provide references for disciplined construction of other organ donation management teams and promote the development of organ donation and transplantation in China.

Objective To compare CT manifestations of pneumocystis jirovecii pneumonia(PCP)and cytomegalovirus pneumonia(CMVP)after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods Totally 21 PCP patients(PCP group)and 26 CMVP patients(CMVP group)after allo-HSCT were retrospectively enrolled,and CT findings were compared between groups.Results Significant differences of distribution patterns of ground glass opacity(GGO)and nodule lesions,lung cysts,the time of condition reached most severe,the proportion of cases with lesions absorption more than 50％ within 30 days,of cases with lesions completely absorbed and the first total severity score(TSS)of GGO were found between groups(all P＜0.05).Conclusion CT manifestations of PCP and CMVP after allo-HSCT were somehow similar,but GGO distributed widerly,with more lung cysts and better prognosis in the former,while GGO distrubuted relatively limitted with diffuse nodules and poor prognosis in the latter.

Purpose To analyze the abnormal CT imaging features of the lungs of adult patients with chronic graft-versus-host disease(cGVHD)and to improve the ability of diagnosis and differentiation of abnormal cGVHD lungs via combining with clinical data.Materials and Methods A retrospective study of 162 patients with clinical manifestations of cGVHD after allogeneic hematopoietic stem cell transplantation in Peking University People's Hospital from October 2018 to October 2020 was conducted.The chest CT images(including lesion location,distribution,ground glass density,consolidation,mesh image,nodule image,bronchiectasis,pleural effusion,gas retention,pneumothorax or mediastinal air)were summarized and the differences of imaging features between pulmonary cGVHD and pulmonary infection were compared.Results Of the 50 fungal infections,43 had single nodules;of the 7 viral infections,4 had diffuse ground glass nodules;2 had diffuse grid shadows,and of the 5 bacterial infections,1 had limited solid shadows.The 36 cases of non-infectious pulmonary complications were all oblusive bronchiolitis,and the CT signs showed gas retention in 32 cases,bronchiectasis in 22 cases,and thickening of the bronchial wall in 27 cases.Conclusion The vast majority of cGVHD patients have abnormal lung imaging,with the main cause of infection.Some patients have imaging manifestations of obliterated bronchiolitis,and imaging combined with clinical practice may be helpful for the diagnosis and differentiation of lung complications.

Objective:To screening differentially expressed genes (DEGs) in proliferative diabetic retinopathy (DR) patients to provide new biological therapeutic targets for proliferative DR (PDR) therapy.Methods:A basic research. A total of 3 PDR patients (group PDR) and 3 non-diabetic patients (control group) were enrolled in the study in Tianjin Medical University Eye Hospital in October 2020. In addition, 40 cases of PDR and non-diabetic patients were selected and divided into PDR validation group and control validation group. Peripheral blood validation test was performed in PDR validation group and control validation group; RNA sequencing was performed in PDR group and control group. Transcriptomics (RNAseq) sequencing technology was used to screen DEG in PDR group and control group. The selected DEGs were analyzed by gene ontology (GO) function enrichment analysis, signal pathway enrichment analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction network (PPI). The gene expression database was used to find the high-throughput data related to PDR, and multi queue comparison analysis was carried out. The target genes of differentially expressed miRNAs were predicted through targetscan platform, so as to clearly screen the correlation between DEG and PDR. Reverse transcription polymerase chain reaction and Western blot were used to verify the expression of DEG mRNA and protein related to PDR. The relative expression of PDR related DEG mRNA and protein between PDR validation group and control validation group were compared by paired t-test. Results:A total of 1 337 DEGs were screened by RNAseq sequencing in the peripheral blood of patients with PDR, of which 419 genes were up-regulated and 918 down-regulated. Among them, direct inhibitor of apoptosis protein-binding protein with low isoelectric point ( DIABLO), zinc finger and BTB domain containing 10 ( ZBTB10), polo-like kinases 3 ( PLK3), regulatory subunit 1 ( PIK3R1) and B cell translocation gene 3 (BTG3) were differentially expressed in PDR patients. The function of GO was enriched from the analysis of molecular function, biological process and cellular composition. The results showed that DIABLO, ZBTB10, PLK3, PIK3R1, BTG3 were involved in the pathological process related to PDR. KEGG enrichment analysis showed that glucose metabolic pathways such as extracellular matrix receptors, cytokine regulatory pathway, p53 signal pathway and galactose metabolism may be involved in the process of differential genes. The analysis of PPI protein interaction network showed that the larger the DEG-associated protein node, the greater the number of associated nodes. Among them, DIABLO, ZBTB10, PLK3, PIK3R1 and BTG3 played significant roles in the formation of the action network. By comparing and analyzing the existing high-throughput data related to diabetic retinopathy in Gene Expression Omnibus database and predicting by Targetscan platform, it was found that some significant differences in miRNA reported in aqueous humor, vitreous fluid and plasma of DR patients can be regulated by the differential genes found in this study. Compared with the control verification group, the relative expressions of DIABLO, ZBTB10, PLK3, PIK3R1 mRNA and protein in peripheral blood of the PDR verification group were up-regulated, and the relative expression of BTG3 mRNA and protein was down-regulated. Conclusion:DIABLO, ZBTB10, PLK3, PIK3R1 and BTG3 are DEGs in patients with PDR, and they can participate in the disease process by regulating the biological processes of cell proliferation, fibrosis and oxidative stress.