BACKGROUND:Accurate early diagnosis and timely reperfusion therapy are important prerequisites for saving the lives and improving the prognosis of patients with acute myocardial infarction.Therefore,it is important to find ideal biomarkers for early diagnosis of acute myocardial infarction.OBJECTIVE:To analyze key genes associated with neutrophils by acute myocardial infarction through bioinformatics and machine learning to explore new biomarkers.METHODS:Differentially expressed genes were identified based on the Gene Expression Omnibus(GEO)database and Limma R package.Deconvolution algorithm was used to explore the immune cells infiltration level.Then,acute myocardial infarction and neutrophils-related biomarkers were screened by weighted gene co-expression network analysis(WGCNA),protein-protein interaction(PPI)networks,machine learning,and functional enrichment analysis.Receiver operating characteristic curve analysis was conducted to assess the diagnostic efficacy of biomarkers for acute myocardial infarction.Targeted drugs for biomarkers were screened through the STITCH and Herb database.Finally,the hospitalized patients who were first diagnosed with acute myocardial infarction in the Department of Cardiology of Affiliated Hospital of Guizhou Medical University from March to June 2023 were used as the experimental group,and the hospitalized patients who had no ischemic changes on electrocardiograms and no stenosis on coronary angiograms during the same period were used as the control group.Peripheral blood of the patients in the two groups was collected.The relative expressions of the genes were verified in the human peripheral blood samples by RT-qPCR.RESULTS AND CONCLUSION:(1)A total of 2 349 differentially expressed genes were obtained,and immune infiltration analysis revealed differences in immune cell scores such as B cells memory,NK cells resting,and Neutrophils between the disease and normal groups.(2)Using WGCNA,two gene modules,ME green and ME turquoise,were found to exhibit the highest correlation with neutrophil fine with acute myocardial infarction.(3)Twenty-four differential module genes were obtained after intersecting with differentially expressed genes.Functional enrichment analysis revealed that they were associated with a variety of processes such as innate immune response and defense response to bacteria.KEGG results showed that they were mainly associated with the tumor necrosis factor signaling pathway.(4)The genes mined by the machine learning algorithm took the intersection to obtain three genes,namely,S100A12,PTCH1,and LOC400499,all of which were greater than 0.7 by the area under the receiver operating characteristic curve in both the GSE48060 and GSE66360 datasets.They were considered as potential biomarkers.(5)Based on the STITCH and Herb databases,11 target drugs were found for S100A12 and a total of 6 target drugs were found for PTCH1.(6)RT-qPCR results showed that S100A12,PTCH1,and LOC400499 were significantly differentially expressed in acute myocardial infarction patients compared with controls(P＜0.05).(7)S100A12,PTCH1,and LOC400499 may be potential diagnostic biomarkers for acute myocardial infarction,but their specificity in relation to acute myocardial infarction needs to be further investigated,in which S100A12 may be a potential target for regulating acute myocardial infarction.

BACKGROUND:Accurate early diagnosis and timely reperfusion therapy are important prerequisites for saving the lives and improving the prognosis of patients with acute myocardial infarction.Therefore,it is important to find ideal biomarkers for early diagnosis of acute myocardial infarction.OBJECTIVE:To analyze key genes associated with neutrophils by acute myocardial infarction through bioinformatics and machine learning to explore new biomarkers.METHODS:Differentially expressed genes were identified based on the Gene Expression Omnibus(GEO)database and Limma R package.Deconvolution algorithm was used to explore the immune cells infiltration level.Then,acute myocardial infarction and neutrophils-related biomarkers were screened by weighted gene co-expression network analysis(WGCNA),protein-protein interaction(PPI)networks,machine learning,and functional enrichment analysis.Receiver operating characteristic curve analysis was conducted to assess the diagnostic efficacy of biomarkers for acute myocardial infarction.Targeted drugs for biomarkers were screened through the STITCH and Herb database.Finally,the hospitalized patients who were first diagnosed with acute myocardial infarction in the Department of Cardiology of Affiliated Hospital of Guizhou Medical University from March to June 2023 were used as the experimental group,and the hospitalized patients who had no ischemic changes on electrocardiograms and no stenosis on coronary angiograms during the same period were used as the control group.Peripheral blood of the patients in the two groups was collected.The relative expressions of the genes were verified in the human peripheral blood samples by RT-qPCR.RESULTS AND CONCLUSION:(1)A total of 2 349 differentially expressed genes were obtained,and immune infiltration analysis revealed differences in immune cell scores such as B cells memory,NK cells resting,and Neutrophils between the disease and normal groups.(2)Using WGCNA,two gene modules,ME green and ME turquoise,were found to exhibit the highest correlation with neutrophil fine with acute myocardial infarction.(3)Twenty-four differential module genes were obtained after intersecting with differentially expressed genes.Functional enrichment analysis revealed that they were associated with a variety of processes such as innate immune response and defense response to bacteria.KEGG results showed that they were mainly associated with the tumor necrosis factor signaling pathway.(4)The genes mined by the machine learning algorithm took the intersection to obtain three genes,namely,S100A12,PTCH1,and LOC400499,all of which were greater than 0.7 by the area under the receiver operating characteristic curve in both the GSE48060 and GSE66360 datasets.They were considered as potential biomarkers.(5)Based on the STITCH and Herb databases,11 target drugs were found for S100A12 and a total of 6 target drugs were found for PTCH1.(6)RT-qPCR results showed that S100A12,PTCH1,and LOC400499 were significantly differentially expressed in acute myocardial infarction patients compared with controls(P＜0.05).(7)S100A12,PTCH1,and LOC400499 may be potential diagnostic biomarkers for acute myocardial infarction,but their specificity in relation to acute myocardial infarction needs to be further investigated,in which S100A12 may be a potential target for regulating acute myocardial infarction.

BACKGROUND:Heterotopic ossification is a dynamic growth process.Diverse heterotopic ossification subtypes have diverse etiologies or induction factors,but they exhibit a similar clinical process in the intermediate and later phases of the disease.Acquired heterotopic ossification produced by trauma and other circumstances has a high incidence. OBJECTIVE:To summarize the molecular biological mechanisms linked to the occurrence and progression of acquired heterotopic ossification in recent years. METHODS:The keywords"molecular biology,heterotopic ossification,mechanisms"were searched in CNKI,Wanfang,PubMed,Embase,Web of Science,and Google Scholar databases for articles published from January 2016 to August 2022.Supplementary searches were conducted based on the obtained articles.After the collected literature was screened,131 articles were finally included and summarized. RESULTS AND CONCLUSION:(1)The occurrence and development of acquired heterotopic ossification is a dynamic process with certain concealment,making diagnosis and treatment of the disease difficult.(2)By reviewing relevant literature,it was found that acquired heterotopic ossification involves signaling pathways such as bone morphogenetic protein,transforming growth factor-β,Hedgehog,Wnt,and mTOR,as well as core factors such as Runx-2,vascular endothelial growth factor,hypoxia-inducing factor,fibroblast growth factor,and Sox9.The core mechanism may be the interaction between different signaling pathways,affecting the body's osteoblast precursor cells,osteoblast microenvironment,and related cytokines,thereby affecting the body's bone metabolism and leading to the occurrence of acquired heterotopic ossification.(3)In the future,it is possible to take the heterotopic ossification-related single-cell osteogenic homeostasis as the research direction,take the osteoblast precursor cells-osteogenic microenvironment-signaling pathways and cytokines as the research elements,explore the characteristics of each element under different temporal and spatial conditions,compare the similarities and differences of the osteogenic homeostasis of different types and individuals,observe the regulatory mechanism of the molecular signaling network of heterotopic ossification from a holistic perspective.It is beneficial to the exploration of new methods for the future clinical prevention and treatment of heterotopic ossification.(4)Meanwhile,the treatment methods represented by traditional Chinese medicine and targeted therapy have become research hotspots in recent years.How to link traditional Chinese medicine with the osteogenic homeostasis in the body and combine it with targeted therapy is also one of the future research directions.(5)At present,the research on acquired heterotopic ossification is still limited to basic experimental research and the clinical prevention and treatment methods still have defects such as uncertain efficacy and obvious side effects.The safety and effectiveness of relevant targeted prevention and treatment drugs in clinical application still need to be verified.Future research should focus on clinical prevention and treatment based on basic experimental research combined with the mechanism of occurrence and development.

Objective:To evaluate the immunogenicity, safety, and immune persistence of the sequential booster with the recombinant protein-based COVID-19 vaccine (CHO cell) in healthy people aged 18-84 years.Methods:An open-label, multi-center trial was conducted in October 2021. The eligible healthy individuals, aged 18-84 years who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, were recruited from Shangyu district of Shaoxing and Kaihua county of Quzhou, Zhejiang province. All participants were divided into three groups based on the differences in prime-boost intervals: Group A (3-4 months), Group B (5-6 months) and Group C (7-9 months), with 320 persons per group. All participants received the recombinant COVID-19 vaccine (CHO cell). Blood samples were collected before the vaccination and after receiving the booster at 14 days, 30 days, and 180 days for analysis of GMTs, antibody positivity rates, and seroconversion rates. All adverse events were collected within one month and serious adverse events were collected within six months. The incidences of adverse reactions were analyzed after the booster.Results:The age of 960 participants was (52.3±11.5) years old, and 47.4% were males (455). The GMTs of Groups B and C were 65.26 (54.51-78.12) and 60.97 (50.61-73.45) at 14 days after the booster, both higher than Group A′s 44.79 (36.94-54.30) ( P value<0.05). The GMTs of Groups B and C were 23.95 (20.18-28.42) and 27.98 (23.45-33.39) at 30 days after the booster, both higher than Group A′s 15.71 (13.24-18.63) ( P value <0.05). At 14 days after the booster, the antibody positivity rates in Groups A, B, and C were 91.69% (276/301), 94.38% (302/320), and 93.95% (295/314), respectively. The seroconversion rates in the three groups were 90.37% (272/301), 93.75% (300/320), and 93.31% (293/314), respectively. There was no significant difference among these rates in the three groups (all P values >0.05). At 30 days after the booster, antibody positivity rates in Groups A, B, and C were 79.60% (238/299), 87.74% (279/318), and 90.48% (285/315), respectively. The seroconversion rates in the three groups were 76.92% (230/299), 85.85% (273/318), and 88.25% (278/315), respectively. There was a significant difference among these rates in the three groups (all P values <0.001). During the sequential booster immunization, the incidence of adverse events in 960 participants was 15.31% (147/960), with rates of about 14.38% (46/320), 17.50% (56/320), and 14.06% (45/320) in Groups A, B, and C, respectively. The incidence of adverse reactions was 8.02% (77/960), with rates of about 7.50% (24/320), 6.88% (22/320), and 9.69% (31/320) in Groups A, B, and C, respectively. No serious adverse events related to the booster were reported. Conclusion:Healthy individuals aged 18-84 years, who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, have good immunogenicity and safety profiles following the sequential booster with the recombinant COVID-19 vaccine (CHO cell).

Objective:To investigate the incidence and risk factors of renal injury in human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) patients with poor immune reconstitution.Methods:The HIV infection/AIDS patients with poor immune reconstitution who were visited Second Department of Infection of Hangzhou Xixi Hospital from January to December 2021 were enrolled. The clinical data and laboratory examinations of the patients were collected, and the relevant risk factors were analyzed by logistic regression.Results:Among 303 HIV infection/AIDS patients with poor immune reconstitution, 59(19.5%) patients had renal injury. Logistic regression analysis showed that hypertension (odds ratio ( OR)=0.200, 95% confidence interval (95% CI) 0.065 to 0.618, P=0.005), taking tenofovir ( OR=0.275, 95% CI 0.130 to 0.580, P=0.001), hypoproteinemia ( OR=1.045, 95% CI 1.006 to 1.086, P=0.022), and low CD4 + T lymphocytes level ( OR=1.009, 95% CI 1.003 to 1.014, P=0.001) were risk factors for renal injury. Conclusions:The incidence of renal injury in HIV infection/AIDS patients with poor immune reconstitution is high. Hypertension, taking tenofovir, hypoproteinemia, and low CD4 + T lymphocytes level are risk factors for renal injury in patients.

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.
Drug Delivery Systems ; Proteins ; Transcriptome

Objective To explore clinical efficacy and mechanisms of medicinal-cake-separated moxibustion treatment for mild-to-moderate ulcerative colitis (UC) of spleen deficiency and dampness type.Methods Totally 60 cases were randomly divided into observation group and control group according to a random digits table, with 30 cases in each group. The control group was inserted into the anus with mesalamine suppository 1 g once a day, while the observation group was given medicinal-cake-separated moxibustion treatment once a day based on the treatment for the control group. Medicinal cake (Aconiti Lateralis Radix Praeparata: Codonopsis Radix: Coptidix Rhizoma: Salviae Miltiorrhizae Radix et Rhizoma: Corydalis Rhizoma: Aucklandiae Radix=3:3:2:2:2:1) was put on the acupoints (Pishu, Zhongwan and Zusanli for the first group, Dachangshu, Tianshu and Shangjuxu for the second group, one group for each time, and 2 groups were used interchangeably). One wormwood cylinder was put on medicinal cake, 5 min each time, 3 doses each time, once a day. The treatment course for all was 8 weeks. The main symptom scores (diarrhea, bellyache, pus and blood stool) and total scores, colonoscopy Baron score and serum CC chemokine ligand 20 (CCL20) expression level were compared between before and after treatment in the two groups. The clinical efficacy was evaluated and the adverse reactions were observed.Results The total effective rate in observation group was 93.33% (28/30) and significantly higher than that of the control group of 76.67% (23/30). After the treatment, the main symptom scores and total scores, colonoscopy Baron score and serum CCL20 expression level were significantly lower than those of pre-treatment in the same one group (P<0.05), which of the observation group were remakably lower than those of the control group (P<0.05); there was one case occured adverse reaction in the observation group and two cases in the control group, with no statistical significance between the two groups (P>0.05).Conclusion Medicinal-cake-separated moxibustion treatment is effective and safe in patients with mild-to-moderate UC of spleen deficiency and dampness type, which effects might be involved in regulating the expression of serum CCL20.

BACKGROUND:ABO-incompatibility between donor and recipient is not a barrier for Successful allogeneic hematopoietic stem cell transplantation even though it is well established that major ABO incompatibility may lead to prolonged destruction of donor-derived erythrocytos and prolonged transfusioil requirements.OBJECTIVE:To explore the effect of ABO.incompatible on clinical characteristics in allogeneic-hematopoietic stem cell transplantation.DESIGN:A retrospective observation.SETTING:Department of Hematology.the Affiliated Drum Tower Hospital of Nanjing University Medical School.PARTICIPANTS:Fourteen patients(11 males and 3 feiliales,aged 15-60 years old)with malignant hematologic diseases who received ABO-incompatible allogeneic hematopoietic stem cell transplantation in the Affiliated Drum Tower Hospital of Nanjing University Medical School from May 2002 to September 2007 Were recruited for this study.Of the 14 patients,7 were human leukocyte antigen(HLA).matched,and the other 7 were HLA-half-matched.Controls were 11 patients who received ABO-compatibility bone marrow transplantation during the same period.Written informed consents for receiving allogeneic hematopoietic stem cell transplantation were obtained from each reciplent.The donors were sibling sister,sibling brother.son and mother,and they all agreed to provide marrow for transplantation.T1lis experiment was given an approval by the Ethics Committees of the hospital.METHODS:Regimen conditioning:HLA-matched transplantation regimen conditioning consisted of busulfan(Bu)and cyclophosphamide(Cy).HLA-half-matched transplantation regimen conditioning adopted GIAC program from Beijing People's Hospital.The GIAC program consisted of 4 parts:G:granulocyte colony-stimulating factors used for donors;I:stronger immunosuppressive regimen conditioning used for recipients;A: antihuman thymocyte globulin added:C: combined transplantation of bone marrow and peripheral blood;Perfusion of hematopoietic stem cells:The marrow from ABO-incompatible donor depleted erythrocytes by hydroxyethyl starch sedimentation.MAIN OUTCOME MEASURES:Adverse reaction.complication and hematologic recovery after ABO-incompatibility stem cell transplantation.RESULTS:One out of fourteen recipients developed pure red cell aplasia(PRCA)and dropped out of final analysis.Hematologic recovery:The median time of erythrocyte recovery after ABO-incompatible stem cell transplantation was delayed compared with ABO compatible stem cell transplantation (t=2.352.P＜0.05).There were no significant difieFences in the recovery of neutrophils and platelets between ABO-incompatible group and ABO-compatible group(P＞0.05).The median time of recovery of the erythrocyte and the blood type switching was delayed in HLA-mis-matched allogeneic hematopoietic stem cell transplantation compared with HLA-matched allogeneic hematopoietic stem cell transplantation,but without significant difference(P＞0.05).Complications:During the stem cell transfusion following transplantation.none of 14 Patieats had hemolytic complications or delayed haemolysis.CONCLUSION:There was no evidence of ABO-incompatibility between donor and recipient is a barrier for successful allogeneic hematopoietic stem cell transplantation.