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A fundamental challenge that arises in biomedicine is the need to characterize compounds in a relevant cellular context in order to reveal potential on-target or off-target effects. Recently, the fast accumulation of gene transcriptional profiling data provides us an unprecedented opportunity to explore the protein targets of chemical compounds from the perspective of cell transcriptomics and RNA biology. Here, we propose a novel Siamese spectral-based graph convolutional network (SSGCN) model for inferring the protein targets of chemical compounds from gene transcriptional profiles. Although the gene signature of a compound perturbation only provides indirect clues of the interacting targets, and the biological networks under different experiment conditions further complicate the situation, the SSGCN model was successfully trained to learn from known compound-target pairs by uncovering the hidden correlations between compound perturbation profiles and gene knockdown profiles. On a benchmark set and a large time-split validation dataset, the model achieved higher target inference accuracy as compared to previous methods such as Connectivity Map. Further experimental validations of prediction results highlight the practical usefulness of SSGCN in either inferring the interacting targets of compound, or reversely, in finding novel inhibitors of a given target of interest.
Subject(s)
Drug Delivery Systems , Proteins , TranscriptomeABSTRACT
Objective To investigate the association of copy number variations (CNVs) in the FCGR3A and FCGR3B genes with different outcomes and disease progression after hepatitis B virus (HBV) infection. Methods Peripheral blood samples were collected from 841 patients with chronic HBV infection and 296 patients with self-limited HBV infection, an according to the degree of disease progression, the patients with chronic HBV infection were further divided into chronic hepatitis B (CHB) group, liver cirrhosis (LC) group, and hepatocellular carcinoma (HCC) group. The AccuCopy technique was used for the quantitative analysis of CNVs in the FCGR3A and FCGR3B genes in peripheral blood. The independent samples t -test was used for comparison of continuous data between two groups, and a one-way analysis of variance and the Kruskal-Wallis H test were used for comparison between multiple groups; the chi-square test was used for comparison of categorical data between groups. The chi-square test was also used to investigate the difference in the distribution of CNVs in the FCGR3 gene between different groups. The age-and sex-adjusted logistic regression model was used to investigate the influence of CNVs on the chronicity of HBV infection. Results There was a significant difference in the frequency distribution of CNVs in the FCGR3A and FCGR3B genes between the chronic HBV infection group and the self-limited HBV infection group ( χ 2 =11.406 and 19.143, both P < 0.05). As for disease progression after chronic HBV infection, there were no significant differences in CNVs of the FCGR3A and FCGR3B genes between the CHB group, the LC group, and the HCC group (FCGR3A: χ 2 =3.125, P =0.537; FCGR3B: χ 2 =5.274, P =0.260). There were also no significant differences in CNVs of the FCGR3A and FCGR3B genes between the HBeAg-positive group and the HBeAg-negative group (FCGR3A: χ 2 =1.025, P =0.599; FCGR3B: χ 2 =0.712, P =0.701). Reduction or deletion of the copy number of the FCGR3A and FCGR3B genes was a risk factor for the chronicity of HBV infection (FCGR3A: odds ratio [ OR ]=0.621, 95% confidence interval [ CI ]: 0.513-0.752; FCGR3B: OR =0.594, 95% CI : 0.491-0.719). Conclusion Reduction or deletion of the copy number of the FCGR3A and FCGR3B genes may be a genetic susceptibility factor for the chronicity of HBV infection, but it is not associated with disease progression.
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【Objective】 To develop an assay to determine β-lactam antibiotics using microcolumn gels and to study the β-lactam antibiotics present in the blood of patients and their clinical significances. 【Methods】 446 patients with a history of taking β-lactam antibiotics from January 2019 to June 2019 were randomly selected from Trauma Emergency Center, Department of Arthrosis, Department of Spine and Department of Bone Oncology of our hospital, and 4 mL(per capita) venous blood was collected. Irregular antibody screening, anti-globulin detection and drug antibody determination were performed by microcolumn gel method. The data of gender, age, disease, blood transfusion history and medication were collected. The test results and clinical data were retrospective analyzed. 【Results】 The yielding rate of antibody was 0.45%(2/446) in patients with a history of taking β -lactam antibiotics. 16.38%(73/446) of the samples were positive in direct antiglobulin test, and 64.38%(47/73) of them did not agglutinate with RBCs treated with drugs. The yielding rate of specific antibodies against drug was 4.93%(22/446), and the titer ranged from 2 to 128(8). 1 case of auto-IgM antibody, 1 case of blood group related antibody and 2 cases of non-specific protein adsorption were detected. The yielding rate of drug antibody in patients with blood transfusion history reached to 12.10 %(22/124), so it was also high in patients with bone tumor. 【Conclusion】 Direct antiglobulin assay is helpful for the detection of β-lactam antibodies. The negative results of antibody screening cannot completely exclude the presence of drug antibodies. The yielding rate of drug antibody can be greatly improved by specific drug antibody detection, and it was higher in transfused patients relative to non-transfused one.
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Objective To evaluate of three-dimensional spiral CT cholangiography to bile duct configuration before laparoscopic cholecystectomy.Methods A retrospective analysis was performed for 60 patients with cholelithiasts concurrent with choledocholithiasis from May 2009 to April 2012,which were treated with endoscopic retrograde cholangiopancreatography (ERCP),endoscopic sphincterotomy (EST),and endoscopic nasobiliary drainage (ENBD),then three-dimensional spiral CT cholangiography(SCTC) was performed through endoscopic nasobiliary drainage (ENBD) tube,and the bile duct tree image of SCTC was evaluated,then laparoscopic cholecystectomy (LC) was carried out.Results Sixty cases were performed three-dimensional SCTC.The left and right hepatic bile ducts,the hepatic bile duct and the common bile duct were visible in 100％ patients,and cholecyst bile duct was visible in 75％patients,and three-dimensional SCTC can tell the position of cholecyst duct and the place where the cholecyst bile duct enteres into the common bile duct.Conclusion Three-dimensional SCTC can show the shape of bile duct tree,especially the cholecyst duct,and has some guidance values to judge the structure of the bile duct tree and the configuration of cholecyst bile duct during operation,which can decrease the possibility of bile duct injure.
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ObjectiveTo study the preoperative evaluation of three-dimensional spiral CTcholangiography(SCTC) in patients with bile duct obstruction.MethodsA retrospective analysis was performed for 60patients with bile duct obstruction from May 2008 to April 2011,who were treated with endoscopic retrograde cholangiopancreatography( ERCP),then SCTC was performed through endoscopic nasobiliary drainage( EN-BD) tube,and the bile duct tree image of SCTC of bile duct obstruction was evaluated.ResultsIn 60 cases of bile duct obstruction who performed three-dimensional SCTC,the left and right hepatic bile ducts,the hepatic bile duct and the common bile duct were visible in 100％ patients,cholecyst bile duct was visible in 80％ patients,and three-dimensional SCTC can tell the position of cholecyst duct and the place where the cholecyst bile duct enters into the common bile duct.ConclusionThree-dimensional SCTC can show the shape of bile duct tree,especially the cholecyst duct,and has some guidance values in judging the structure of the bile duct tree and the shape of cholecyst bile duct during operation.
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The purpose of the study was to investigate the impact of rat cytomegalovirus(RCMV) infection on the development of the nervous system in rat embryos,and to evaluate the involvement of Wnt signaling pathway key molecules and the downstream gene neurogenin 1(Ngn1) In RCMV infected neural stem cells(NSCs).Infection and control groups were established,each containing 20 pregnant Wistar rats.Rats in the infection group were inoculated with RCMV by intraperitoneal injection on the first day of pregnancy.Rat E20 embryos were taken to evaluate the teratogenic rate.NSCs were isolated from E13 embryos,and maintained in vitro.We found:1) Poor fetal development was found in the infection group with low survival and high malformation rates.2) The proliferation and differentiation of NSCs were affected.In the infection group,NSCs proliferated more slowly and had a lower neurosphere formation rate than the control.The differentiation ratio from NSCs to neurons and glial cells was significantly different from that of the control,showed by immunofluorescence staining.3) Ngn1 mRNA expression and the nuclear β-catenin protein level were significantly lower than the control on day 2 when NSCs differentiated.4) The Morris water maze test was performed on 4-week pups,and the infected rats were found worse in learning and memory ability.In a summary,RCMV infection caused abnormalities in the rat embryonic nervous system,significantly inhibited NSC proliferation and differentiation,and inhibited the expression of key molecules in the Wnt/β-catenin signaling pathway so as to affect NSCs differentiation.This may be an important mechanism by which RCMV causes embryonic nervous system abnormalities.
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Objective To investigate the expression of nuclear factor kappa B (NF-κB),tumor necrosis factor α (TNF-α) and interleukin6 (IL-6) in human colorectal carcinoma tissues,and to explore their clinical significances in the genesis and development of colorectal cancer.Methods Sixty cases of colorectal cancer tissues and 36 cases of colorectal adenoma tissues were collected,60 cases of paracancerous normal colorectal tissues were the controls.Immunohistochemistry SABC method was used to detect the expression of NF-κB,TNF-α and IL-6 in each group respectively.The correlation of NF-κB,TNF-α and IL-6 with clinical pathologic features of colorectal cancer was analyzed.Results In colorectal carcinoma,adjacent normal colorectal tissues and colorectal adenoma tissues the positive expression rates of NF-κB were 76.7 ％ (46/60),46.7 ％ (28/60),83.3 ％ (30/36),the positive rates of TNF-α were 70.0 ％ (42/60),36.7 ％ (22/60),66.7 ％(24/36),the positive rates of IL-6 were 80.0 ％ (48/60),43.3 ％ (26/60),61.1％ (22/36).The differences were significant in each group (all P ＜ 0.05).The expression of NF-κB was closely associated with the expression of TNF-α and IL-6 respectively.In addition,the expression of NF-κB and TNF-α were correlated with vascular invaded,lymphnode metastasis and different stages.The expression of IL-6 was correlated with lymphnode metastasis and different stages.Conclusion The over expression of NF-κB and the downriver inflammation factors have close relationship with biological behaviors of colorectal cancer.It may be considered that the pathway of NF-κB play an important role in the genesis and development of colorectal cancer.
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Objective To study the preventive effect of biliary duct injury(BDI)of three-dimensional spiral CT cholangiography(SCTC)before laparoscopic cholecystectomy(LC).Methods A retrospective analysis was carried out for 30 patients suffering from cholelithiasts concurrent with choledocholithiasis from July 2007 to June 2009.EAndoscopic sphincterotomy(EST),then three-dimensional SCTC was carried out through endoscop-ic nasobiliary drainage(ENBD)before IX,and the preventive effect of BDI was evaluated.Results The visibility of intra-hepatic bile duct,the hepatic bile duct and the common bile duct were 100% the visibility of chol-ecyst bile duct was 73% ,and three-dimensional SCTC can tell the position of cholecyst duct,BDI was not happened in all these patients.Conclusion Three-dimensional SCTC before LC can decrease the possibility of BDI.
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Objective To evaluate the efficacy and toxicity of hyperthermia combined with chemoradiotherapy for local advanced cervical cancer. Methods Sixty-eight patients with local advanced cervical cancer were treated. Each patient was given cisplatin at the dose of 20 mg ivgtt dl -2 and 5 -fluorouracil 0.75 ivgtt dl -2, repeating every week, total 3 weeks. Thirty -eight patients received chemoradiotherapy alone. Thirty patients received hyperthermia with deeply focus technology, the temperature was increased and maintained 42.5 ℃ for 30 min at least, within 2 hours following irridiation. Hyperthermia was given twice per week with 7 or 12 sessions, as the same chemoradiation methods as the reference group.After 40 Gy therapy to estimate by cervical examination and ultrasonography, the patients with down stage were for operation, and the others continued to irridiation and additional brachytherapy with californium 252until radical dose. Results All patients were tolerated, fifteen patients of hyperthermia combined group were operated and ten patients of the reference group were operated, the difference was significance (50.0 % vs.26.3 %, P <0.05). The response rate of the combined group was 90.0 %, and the reference group was 84.2 %.The incidence of radiotherapy toxicity of the combined group was not higher than the reference group.Conclusion Hyperthermia combined with chemoradiotherapy can elevate the resection rate and the local control rate, not increase the radiotherapy toxicity and increase quality of life for cervical cancer patients.
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BACKGROUND:The human body pulse signal can be regarded as the convolution of the heart excitation resource signal and the pulse transfer system. The backward signal was studied more before, but the research to the forward signal is not enough.OBJECTIVE: To extract the heart excitation source signals in human pulse wave.DESIGN: A randomized controlled design.SETTING: Second Affiliated Hospital of China Medical University;Biomedical Engineering institute of Shandong University.PARTICIPANTS: Health physical-examined persons in the Second Affiliated Hospital of China Medical University on March 11,2004 were recurited. RM6240 physiological signals collection system was adopted.METHODS: The collection of pulse wave in healthy persons was input into system-analysis mode and based on the principle of blind deconvolution and feasible arithmetic, heart source signals were obtained.MAIN OUTCOME MEASURES: ①Normal human pulse wave ②The heart excitation source signals.RESULTS: In the back-half segment of cepstrum (n＞ n0), periodic impulse was in accordance with the basic human pulse frequency. There was an excitation source in the pulse wave. If high-pass filter was defined to the signal (when n0 equals to 30 in the experimentation the result will be best.), we could get the heart excitation source signal after it was filtered, F transformation, index and inverse transformation.CONCLUSION: This method is practical and feasible and will provide a basis to further analyze pulse wave.