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 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.

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.

"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.

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.

Objective:To observe the effect of bone morphogenetic protein 4 (BMP4) on the proliferation and migration of human retinal microvascular endothelial cells (hRMEC) under oxidative stress.Methods:The hRMEC cultured in vitro were divided into control group, 4-hydroxynonenal (HNE) treatment group (4-HNE group), 4-HNE+BMP4 group (BMP4 group). Cell culture medium of 4-HNE treatment group was added with 10 μmmol/L 4-HNE; cell culture of BMP4 group was cultured with 10 μmmol/L 4-HNE, and after stimulation for 6 h, 100 ng/ml recombinant human BMP4 was added. The effects of 4-HNE and BMP4 on hRMEC viability was detected by thiazole blue colorimetric method. The effects of 4-HNE and BMP4 on cell migration was determined by cell scratch test. The relative expression of BMP4 mRNA in the cells of the control group and 4-HNE treatment group and the mRNA expression of the control group, the fibronectin (FN) of BMP4 group, laminin (Laminin), α-smooth muscle contractile protein (α-SMA), and collagen type Ⅰ (Collagen Ⅰ), vascular endothelial growth factor (VEGF), and connective tissue growth factor (CTGF) were detected by real-time quantitative polymerase chain reaction (qRT-PCR). Western blot was used to detect the relative expression of BMP4 protein in the control group and 4-HNE group. The control group and 4-HNE group were compared by t test. Results:Compared with the control group, cell viability ( t=12.73, 16.26, P=0.000 2, <0.000 1), cell migration rate ( t=28.17, 37.48, P<0.000 1, <0.000 1) in 4-HNE group and BMP4 group were significantly increased, and the difference was statistically significant; the relative expression of BMP4 mRNA and protein in the 4-HNE group was significantly increased, and the difference was statistically significant ( t=16.36, 69.35, P=0.000 1, <0.000 1). The qRT-PCR test results showed that compared with the control group, the relative expression of VEGF, FN, Laminin, α-SMA, Collagen Ⅰ, and CTGF mRNA in the cells of the BMP4 group was significantly increased, and the difference was statistically significant ( t=10.61, 17.00, 14.85, 7.78, 12.02, 10.61, P=0.0004, <0.000 1, 0.000 1, 0.001 5, 0.000 1, 0.000 4). Conclusion:BMP4 can induce the proliferation and migration of hRMEC; it can also regulate the expression of angiogenesis factors and fibrosis-related factors in hRMEC.

Objective By analyzing the perioperative management in our hospital to explore the clinical effect and safety of single kidney transplantation from deceased juveniles' donors.Methods We retrospectively analyze 86 cases of kidney transplantations from deceased juveniles' donors in our hospital from 2007 December to 2015 August.Results The success rate of the operations was 100％.The postoperative complications occurred as fellows:7 cases of acute rejection (8.14％);10 cases of drug intoxication (11.62％);21 cases of DGF (24.44％),4 cases of leakage of urine (4.65％),7 cases of lung infection (8.14％).Two cases (2.32％) died after the operation because of serious lung infection,and by corresponding treatment 47 cases recovered after 2-4 weeks.The creatinine level in 37 cases without any complications was 131.88 ± 44.20 μmol/L during discharge.Conclusion With strict selection,the organ from a deceased juvenile donor is safe and practicable.

Objective To investigate the relationship between.serum 25-hydroxy vitamin D (25OHD) and parathyroid hormone (PTH) with the severity in elderly patients with osteoporosis.Methods A total of 160 patients with fractures treated in this hospital from January 2015 to January 2016 were selected and divided into the normal bone mass group(53 cases),osteopenia group (63 cases) and osteoporosis group(44 cases) according to the bone mineral density (BMD) in the lumbar vertebra 1-4,total hip and femoral neck any position.Then the serum levels of 25OHD,PTH,T value of BMD,serum osteocalcin (BGP) and bone alkaline phosphatase (ALP) were compared among 3 groups.Results The serum PTH detection value had no statistically significant difference among the normal group,osteopenia group and osteoporosis group (P＞0.05).The serum 25OHD level in the normal group was higher than that in the osteopenia group and osteoporosis group (P＜0.05);the serum BGP and.ALP levds in the normal group were significantly lower than those in the osteopenia group and osteoporosis group (P＜0.05).The level of serum 25OHD in the osteopenia group was higher than that in the osteoporosis group (P＜0.05).The level of serum BGP and ALP in the osteopenia group was significantly lower than that in the osteoporosis group (P＜0.05).The BMD value of the lumbar vertebra 1-4,total hip and femoral neck in the normal group was significantly higher than that in the steopenia group and osteoporosis group (P＜0.05).There was a significant positive correlation between serum 25OHD and the BMD value in lumbar vertebra 1-4,total hip joint and femoral neck (P＜0.05).Conclusion The level of serum 25OHD is significantly decreased in the patients with osteoporosis,and.is positively correlated with the BMD level.

Objective To study the role of natural antiox-LDL subclass IgM antibodies in formation of atherclerosis.Methods The macrophages from mice were divded into LDL group,Cuox-LDL group and control group.The macrophages in LDL group and Cuox-LDL group were precultured with LDL and Cuox-LDL.Adhesion experiment was performed in control group.3A6,5G8 and 2H7 were incubated.The macrophages were divided into 3A6 group,5G8 group and 2H7 group.Adhesion experiment was performed by adding the pretreated 125I Cuox-LDL.The binding parameters of macrophages and 125I Cuox-LDL in different groups were recorded.Foam cells were analyzed by cell lipid analysis with oil red O staining.Results The bound 125I Cuox-LDL level was significantly lower in Cuox-LDL group than in control group and LDL group (P＜0.01).No significant difference was found in bound 125I Cuox-LDL level between 5G3 group and 2H7 group (P＞0.05).The bound 125I Cuox-LDL level was significantly lower in 3A6 group than in control group,5G8 group and 2H7 group (P＜0.01).Oil red O staining showed no oil drop in macrophages,but a small number of oil drops in 3A6 group and a large number of oil drops in control group.The cholesterol and TG in macrophages reduced 45％ and the TG reduced 170％ in 3A6 group,which were significantly lower than those in control group (P＜0.01).Conclusion Antiox-LDL IgM subclass antibody 3A6 can effectively prevent the binding of unactivated macrophages to ox-LDL,reduce the occurrence and progression of atherosclerosis.