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Objectives Objectives To investigate how the imbalance of innate lymphoid cells (ILCs)in the peripheral blood of patients with lung adenocarcinoma affects the balance of downstream mononuclear macrophages and T helper (Th) cells, and to identify the impact of the imbalance of ILCs on the immune status and prognosis of lung adenocarcinoma. Methods The peripheral blood of 20 patients with lung adenocarcinoma and normal controls were collected. The percentage of ILCs, mononuclear macrophages and T lymphocyte in peripheral blood were analyzed by flow cytometry. The characteristic cytokine secretion levels of various types of immune cells in peripheral blood were detected by real-time fluorescence quantitative PCR. Results Compared with the normal controls, the proportion of M2 mononuclear macrophages, ILC1 and ILC2 in patients with lung adenocarcinoma was up-regulated, while the proportion of M1 mononuclear macrophages, CD4+ T and CD8+ T was down-regulated. The mRNA expression of related cytokines of M1 mononuclear macrophages and ILC1 were decreased; while the mRNA expression of related cytokines of M2 mononuclear macrophages and ILC2 were increased. Along with the decreased CD4+T cells-associated cytokine T-bet mRNA expression, and the increased GATA3 mRNA expression. Moreover, the expression of PD-1 in CD8+ T cells was also up-regulated. Conclusion The imbalance of ILCs in peripheral blood of patients with lung adenocarcinoma promotes the imbalance of mononuclear macrophages and Th cells, which altogether maintains the immunosuppression in patients with lung adenocarcinoma, and promotes the development of lung adenocarcinoma.
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Humanos , Linfócitos , Imunidade Inata , Linfócitos T CD8-Positivos , Citocinas/metabolismo , Adenocarcinoma de Pulmão , Terapia de Imunossupressão , RNA MensageiroRESUMO
Objective:To investigate the risk factors of infection with polymyxin resistant and carbapenemase-resistant Klebsiella pneumoniae(PR-CRKP). Methods:A total of 170 patients with CRKP infection admitted in the Third Affiliated Hospital of Soochow University from July 2020 to October 2023 were enrolled,including 123 cases of CRKP infection and 47 cases of PR-CRKP infection. The general conditions,exposure of antibacterial drugs 6 months before admission,laboratory test indicators at admission,antibacterial drug use when target bacteria were detected,length of hospital stay and time of invasive procedures in two groups were retrospectively analyzed. The risk factors of PR-CRKP infection were analyzed with univariate and multivariate logistic regression. SPSS 26.0 software was used to analyze the data.Results:Univariate analysis showed that compared with the CRKP group,the average age of patients in PR-CRKP group was older( Z = -2.186, P = 0.029),the proportion of patients with exposure history to semisynthetic penicillins,carbapenems,polymyxins,and quinolones 6 months before admission was higher( χ 2= 3.930,5.414,11.939,8.478,all P < 0.05),the proportion of infections diagnosed at admission and blood urea nitrogen levels( χ 2= 7.268, Z = -2.406, P = 0.007 and 0.016)was higher,the hemoglobin level( t = 2.641, P = 0.009)was lower,the length of hospital stay was longer,the rates of tracheal intubation,urinary catheter,and deep vein catheterization were higher( Z = -4.243,-4.660,-5.341,-4.583,all P < 0.001),the duration of carbapenem and polymyxin B use was longer( Z = -4.757,-7.554,both P < 0.001),the proportion of combined quinolone-resistant Escherichia coli(QREC)and carbapenem-resistant organism(CRO)infections and bloodstream infections,and the rate of admission to intensive care units was higher( χ 2 = 33.737,42.041,5.426,12.991, P < 0.05 or < 0.01). Multivariate analysis showed that time to polymyxin B use( OR = 1.179, 95%CI 1.059-1.312, P = 0.003),combined QREC infection( OR = 5.357, 95%CI 2.100-13.669, P < 0.001)and combined CRO infection( OR = 3.302, 95%CI 1.146-9.514, P= 0.027)were independent risk factors for PR-CRKP. Conclusion:Prolonged use of polymyxin B is an independent risk factor for PR-CRKP,and mixed QREC and CRO infection can increase the risk of PR-CRKP.
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Ubiquitination modifications are a kind of post-translational modifications of proteins widely found in eukaryotes and involved in a variety of biological activities. E3 ubiquitin ligases are an important component of the ubiquitin system, with the function of specific recognition of substrate proteins and mediation of different types of ubiquitination modifications. They can regulate the function and life time of substrate proteins. Recent studies have shown that E3 ubiquitin ligases are widely involved in the regulation of the host innate immune response and can directly or indirectly influence viral infection. Moreover, viruses are able to encode or hijack E3 ubiquitin ligases in their long-term evolution, allowing them to play an important role in viral infection and replication cycle. This paper reviewed the progress in the mechanisms of E3 ubiquitin ligases in innate immune responses and viral infection in recent years.
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A novel beta-coronavirus, SARS-CoV-2, emerged in late 2019 and rapidly spread throughout the world, causing the COVID-19 pandemic. However, the origin and direct viral ancestors of SARS-CoV-2 remain elusive. Here, we discovered a new SARS-CoV-2-related virus in Yunnan province, in 2018, provisionally named PrC31, which shares 90.7% and 92.0% nucleotide identities with SARS-CoV-2 and the bat SARSr-CoV ZC45, respectively. Sequence alignment revealed that several genomic regions shared strong identity with SARS-CoV-2, phylogenetic analysis supported that PrC31 shares a common ancestor with SARS-CoV-2. The receptor binding domain of PrC31 showed only 64.2% amino acid identity with SARS-CoV-2. Recombination analysis revealed that PrC31 underwent multiple complex recombination events within the SARS-CoV and SARS-CoV-2 sub-lineages, indicating the evolution of PrC31 from yet-to-be-identified intermediate recombination strains. Combination with previous studies revealed that the beta-CoVs may possess more complicated recombination mechanism. The discovery of PrC31 supports that bats are the natural hosts of SARS-CoV-2.
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Although a variety of SARS-CoV-2 related coronaviruses have been identified, the evolutionary origins of this virus remain elusive. We describe a meta-transcriptomic study of 411 samples collected from 23 bat species in a small (~1100 hectare) region in Yunnan province, China, from May 2019 to November 2020. We identified coronavirus contigs in 40 of 100 sequencing libraries, including seven representing SARS-CoV-2-like contigs. From these data we obtained 24 full-length coronavirus genomes, including four novel SARS-CoV-2 related and three SARS-CoV related genomes. Of these viruses, RpYN06 exhibited 94.5% sequence identity to SARS-CoV-2 across the whole genome and was the closest relative of SARS-CoV-2 in the ORF1ab, ORF7a, ORF8, N, and ORF10 genes. The other three SARS-CoV-2 related coronaviruses were nearly identical in sequence and clustered closely with a virus previously identified in pangolins from Guangxi, China, although with a genetically distinct spike gene sequence. We also identified 17 alphacoronavirus genomes, including those closely related to swine acute diarrhea syndrome virus and porcine epidemic diarrhea virus. Ecological modeling predicted the co-existence of up to 23 Rhinolophus bat species in Southeast Asia and southern China, with the largest contiguous hotspots extending from South Lao and Vietnam to southern China. Our study highlights both the remarkable diversity of bat viruses at the local scale and that relatives of SARS-CoV-2 and SARS-CoV circulate in wildlife species in a broad geographic region of Southeast Asia and southern China. These data will help guide surveillance efforts to determine the origins of SARS-CoV-2 and other pathogenic coronaviruses.
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Background@#The H5 avian influenza viruses (AIVs) of clade 2.3.4.4 circulate in wild and domestic birds worldwide. In 2017, nine strains of H5N6 AIVs were isolated from aquatic poultry in Xinjiang, Northwest China. @*Objectives@#This study aimed to analyze the origin, reassortment, and mutations of the AIV isolates. @*Methods@#AIVs were isolated from oropharyngeal and cloacal swabs of poultry. Identification was accomplished by inoculating isolates into embryonated chicken eggs and performing hemagglutination tests and reverse transcription polymerase chain reaction (RT-PCR). The viral genomes were amplified with RT-PCR and then sequenced. The sequence alignment, phylogenetic, and molecular characteristic analyses were performed by using bioinformatic software. @*Results@#Nine isolates originated from the same ancestor. The viral HA gene belonged to clade 2.3.4.4B, while the NA gene had a close phylogenetic relationship with the 2.3.4.4C H5N6 highly pathogenic avian influenza viruses (HPAIVs) isolated from shoveler ducks in Ningxia in 2015. The NP gene was grouped into an independent subcluster within the 2.3.4.4B H5N8 AIVs, and the remaining six genes all had close phylogenetic relationships with the 2.3.4.4B H5N8 HPAIVs isolated from the wild birds in China, Egypt, Uganda, Cameroon, and India in 2016–2017, Multiple basic amino acid residues associated with HPAIVs were located adjacent to the cleavage site of the HA protein. The nine isolates comprised reassortant 2.3.4.4B HPAIVs originating from 2.3.4.4B H5N8 and 2.3.4.4C H5N6 viruses in wild birds. @*Conclusions@#These results suggest that the Northern Tianshan Mountain wetlands in Xinjiang may have a key role in AIVs disseminating from Central China to the Eurasian continent and East African.
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Ubiquitin is a widespread form of post-translational modification of proteins in cells, which plays an important role in regulating immune response, inflammatory response, cell connection, cell cycle, apoptosis, DNA damage repair and many other life processes. The ubiquitin modification of proteins is also reversible. Deubiquitinating enzymes regulate the life span or function of proteins through hydrolyzing polyubiquitin chains to deubiquitinate substrate proteins, thus playing a role in ubiquitin-mediated signal transduction pathways. Ovarian tumor-associated proteases (OTUs) belong to the cysteine family. It has been found that many members of the OTUs family are closely related to the regulation of viral infection. This paper reviewed the role and mechanism of OTUs in host antivirus response in recent years.
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The treatment of advanced breast cancer is mainly palliative treatment. Endocrine therapy is the main treatment for hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer patients without visceral crisis or life-threatening conditions. The goal of endocrine therapy is to prolong survival, improve or maintain quality of life, and delay the start of chemotherapy as much as possible. In recent years, cyclin-dependent kinase 4/6 (CDK4/6) inhibitors have been approved and used clinically. CDK4/6 inhibitors are a new type of targeted therapy drugs, which are mainly used in HR+/HER2- breast cancer patients, making a breakthrough in related endocrine therapy models. Currently, the CDK4/6 inhibitors approved by the US Food and Drug Administration are Palbociclib, Ribociclib and Abemaciclib. Compared with traditional endocrine therapy alone, CDK4/6 inhibitor combined with endocrine therapy significantly prolongs the progression-free survival of breast cancer patients, and is well tolerated. In this paper, the clinical research progress in CDK4/6 inhibitor combined with endocrine therapy for HR+/HER2- breast cancer was introduced, and the adverse reactions of three CDK4/6 inhibitors mentioned above in clinical application were analyzed.
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Background@#The H5 avian influenza viruses (AIVs) of clade 2.3.4.4 circulate in wild and domestic birds worldwide. In 2017, nine strains of H5N6 AIVs were isolated from aquatic poultry in Xinjiang, Northwest China. @*Objectives@#This study aimed to analyze the origin, reassortment, and mutations of the AIV isolates. @*Methods@#AIVs were isolated from oropharyngeal and cloacal swabs of poultry. Identification was accomplished by inoculating isolates into embryonated chicken eggs and performing hemagglutination tests and reverse transcription polymerase chain reaction (RT-PCR). The viral genomes were amplified with RT-PCR and then sequenced. The sequence alignment, phylogenetic, and molecular characteristic analyses were performed by using bioinformatic software. @*Results@#Nine isolates originated from the same ancestor. The viral HA gene belonged to clade 2.3.4.4B, while the NA gene had a close phylogenetic relationship with the 2.3.4.4C H5N6 highly pathogenic avian influenza viruses (HPAIVs) isolated from shoveler ducks in Ningxia in 2015. The NP gene was grouped into an independent subcluster within the 2.3.4.4B H5N8 AIVs, and the remaining six genes all had close phylogenetic relationships with the 2.3.4.4B H5N8 HPAIVs isolated from the wild birds in China, Egypt, Uganda, Cameroon, and India in 2016–2017, Multiple basic amino acid residues associated with HPAIVs were located adjacent to the cleavage site of the HA protein. The nine isolates comprised reassortant 2.3.4.4B HPAIVs originating from 2.3.4.4B H5N8 and 2.3.4.4C H5N6 viruses in wild birds. @*Conclusions@#These results suggest that the Northern Tianshan Mountain wetlands in Xinjiang may have a key role in AIVs disseminating from Central China to the Eurasian continent and East African.
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The unprecedented epidemic of pneumonia caused by a novel coronavirus, HCoV-19, in China and beyond has caused public health concern at a global scale. Although bats are regarded as the most likely natural hosts for HCoV-191,2, the origins of the virus remain unclear. Here, we report a novel bat-derived coronavirus, denoted RmYN02, identified from a metagenomics analysis of samples from 227 bats collected from Yunnan Province in China between May and October, 2019. RmYN02 shared 93.3% nucleotide identity with HCoV-19 at the scale of the complete virus genome and 97.2% identity in the 1ab gene in which it was the closest relative of HCoV-19. In contrast, RmYN02 showed low sequence identity (61.3%) to HCoV-19 in the receptor binding domain (RBD) and might not bind to angiotensin-converting enzyme 2 (ACE2). Critically, however, and in a similar manner to HCoV-19, RmYN02 was characterized by the insertion of multiple amino acids at the junction site of the S1 and S2 subunits of the Spike (S) protein. This provides strong evidence that such insertion events can occur in nature. Together, these data suggest that HCoV-19 originated from multiple naturally occurring recombination events among those viruses present in bats and other wildlife species.
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Objective:A multi-center and large sample volume study was conducted on the verification and improvement of the early established criteria for intelligent routine urinalysis validation (including the microscopic review rules and manual validation rules, referred to as intelligent criteria for short), in order to improve the clinical application of this intelligent criteria.Methods:A total of 31 456 urine specimens were collected from the inpatients and outpatients in six hospitals in China, from March to September 2019. Firstly, 3105 specimens were analyzed for preliminary verification and improvement of the intelligent criteria based on the results of the microscopic examination and manual validation. Secondly, 28 351 specimens were used to verify the clinical application of the improved intelligent criteria. All samples were manually validated as reference.Results:The approval inconsistency rate of the manual validation rules in the original intelligent criteria was 8.59% (202/2 352), and the interception inconsistency rate was 8.84% (208/2 352). The false negative rate and the microscopic review rate of the microscopic review rules were similar to the previous results. Based on an in-depth analysis of big data and the discussions by senior technicians from eight hospitals, one microscopic review rules and four manual validation rules were added, meanwhile two manual validation rule was deleted. The manual validation standards were unified. Finally, the intelligent criteria was improved. Based on the improved intelligent criteria, for microscopic review rules, the false positive rate, false negative rate (misdiagnosis rate), and microscopic review rate did not change significantly, which were 14.72% (457/3 105), 4.06% (126/3 105), and 24.73% (768/3 105), respectively. The approval inconsistency rate and the interception inconsistency rate of manual validation rules were both reduced to 0; the total manual validation rate of the intelligent criteria was 50.89% (1 580/3 105), and the auto-validation rate was 49.11% (1 525/3 105). The large sample volume verification results were consistent with the preliminary verification results of the improved intelligent criteria.Conclusion:This multi-center and large sample volume study had shown that the improved intelligent criteria had better clinical performance.
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Objective@#To detect antibodies to Coxsackievirus B4 (CV-B4), the indirect enzyme-linked immunosorbent assay (ELISA) method was established and optimized using the recombinant VP1 protein expressed in the prokaryote system as the envelope antigen.@*Methods@#The VP1 gene of CV-B4 was amplified using reverse transcriptase-polymerase chain reaction (RT-PCR). It was ligated into the expression vector pET32a(+ ) to obtain the recombinant plasmid pET32(+ )-VP1 and was then transformed into E. coli expression strain Rosetta (DE3). The recombinant VP1 protein was induced by IPTG, which was verified using SDS-PAGE electrophoresis and mass spectrometry. The establishment and optimization of the indirect ELISA reaction system was based on the purified recombinant protein mentioned above as the coating antigen.@*Results@#The CV-B4 VP1 gene was stably expressed in E. coli in the form of inclusion body. The optimal coating concentration of antigen was 7.5 μg per well and the optimal serum dilution was 1∶100. The threshold for determining the negative and positive result of the serum samples was the optical density value of ≥ 0.376 at 450 nm. The purified recombinant protein could be specifically recognized by CV-B4 positive serum without cross-reaction with Coxsackievirus (CV)-A, CV-B1 and CV-B5, indicating that it has good immunogenicity. However, it can cross-react with CV-B3 serum samples.@*Conclusions@#The indirect ELISA detection method based on the CV-B4 VP1 protein could be used in the detection of serum antibody to CV-B4 infection with good sensitivity, specificity and repeatability.
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Objective@#To analyze the genetic characteristics of Coxsackievirus A4 isolated from Taian, 2017-2018.@*Methods@#Sixty throat swab samples of the children who visited Taian Maternal and Child Health Hospital during the year 2017-2018 and were diagnosed as hand, foot and mouth disease, were collected and aseptically inoculated. Fluorescent quantitative PCR analysis was performed using the universal primer for enteroviruses. The high-throughput sequencing was applied to the enterovirus-positive samples, and the full-length genome sequences of the viruses were obtained. Phylogenetic analysis was performed using Mega5.05 and RaxML respectively, and sequence homology and amino acid mutation sites were also analyzed using Mega5.05.@*Results@#Four whole genome sequences of CV-A4 isolated from infants aged 17-19 months old were obtained. Phylogenetic analysis of the full length CV-A4 genomes showed that apart from MG550920/AA/Henan/2016, the remaining CV-A4 strains from China (97.2%), including the four strains from Taian, fell within Group 3. The VP1 genes could be classified into four genotypes and 98.5% of the Chinese strains belonged to genotype D, and the four strains from Taian belonged to D2. It was notable that the Taian isolate A1/Taian is closely related to two strains C179 and C062 from Australia both in the complete genome and the VP1 gene, as well as one strain YT184R isolated from Yantai in 2016 by us. Compared with the prototype CV-A4 strain High Point, 18 amino acid mutations were found in the P1 region.@*Conclusions@#Both phylogenetic trees estimated using the complete genome and the VP1 gene sequences revealed that the four CV-A4 isolates from Taian fell within the same clade with the majority of CV-A4 strains circulating in China. Compared with the prototype CV-A4 strain, several amino acid variations have occurred in the P1 region, which warrants further investigation.
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Objective@#To investigate the drug resistance and positive virulence genes of Acinetobacter baumannii (A.baumannii) and analyze the correlation between drug resistance and the positive pattern of virulence genes. @*Methods@#A total of 67 strains of A.baumannii were collected and identified by matrix assisted laser desorption ionization time of flight mass spectrometry technology (MALDI-TOF MS). Drug susceptibility tests were carried out by turbidimetric and redox indicator method. The homology of A.baumannii stains was explored by cluster analysis. The 8 virulence genes including bacterial outer membrane protein (ompA), biofilm formation (adeH, csuA, pgaA), iron uptake system (basJ), phospholipase D (plcD), capsular positive phenotype (ptk) and regulation of quorum sensing system (abaI) were amplified by PCR and sequenced. The correlation between virulence genes and drug resistance in the 67 strains of A. baumannii was investigated. @*Results@#The positive rates of virulence genes ompA, adeH, csuA, pgaA, abaI, basJ, ptk and plcD were 94%, 100%, 94%, 99%, 93%, 96%, 82% and 99%, respectively. Among the 67 strains of A. baumannii, 3 genes were simultaneously detectable in 1 strain (1.5%), 5 genes were positive in 2 strains (3.0%), 6 genes were positive in 2 strains (3.0%), 7 genes were positive in 14 strains (20.9%) and all the 8 genes were positive in 48 strains (71.6%). Among the 48 strains with 8 positive virulence genes, the drug resistance rate of polymyxin was only 2.1%, but tetracycline was 58.2%, piperacillin and other 13 antibiotics was more than 80%. The 14 strains with 7 positive virulence genes showed more than 78% of resistance rate for all the tested antibiotics except for tetracycline and polymyxin. Cluster analysis showed that the 67 strains of A. baumannii were divided into 2 genotypes: A (41 strains) and B (26 strains). The 41 strains of A type were divided into A1 (27 strains) and A2 (14 strains) subtypes. The strains of A1 subtype were mainly from neurosurgery department (7 strains), ICU (5 strains) and pneumology department (3 strains). The strains of A2 subtype were mainly from pneumology department (3 strains), cardiothoracic surgery department (3 strains), ICU (2 strains) and neurosurgery department (2 strains). The 26 strains of B type were divided into B1 (19 strains) and B2 (7 strains). The strains of B1 type were mainly from ICU (7 strains), neurosurgery department (4 strains) and respiratory department (3 strains). The strains of B2 type were mainly from ICU (2 strains) and respiratory department (3 strains). @*Conclusion@#The cross infection from A. baumannii may present in our hospital. There was no correlation between drug resistance and positive pattern of virulence gene in Acinetobacter baumannii.
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OBJECTIVE: To learn from the implementation experience of UK Strategy for Rare Diseases, and to provide reference for the formulation of the rare disease guarantee strategy in China. METHODS: The background, status quo and content of UK Strategy for Rare Diseases were introduced; its implementation experience was analyzed and summarized to provide enlightenment to the construction of relevant mechanism in China. RESULTS & CONCLUSIONS: British government took measure like strengthening the collection of message, improving service quality and uniting patient organization for patient empowerment, while spreading advanced disease screening and gene detection technology, developping training in diagnosis and treatment of rare disease and encouraging patients to participate in the research. The comprehensive and perfect guarantee system of rare disease had been formed. British experience is worth learning. Our country should construct comprehensive guarantee framework of rare disease, support patient organizations, improve service system for patient and strengthen rare disease research to provide health guarantee for rare disease patients.
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Objective:To analyze the role of clinical pharmacists played in the drug consultation and advice in orthopedic ward in order to discuss the work mode and the effects of clinical pharmacists in orthopedic ward and improve the service quality of clinical pharmacy. Methods:The work records related to the drug treatment of clinical pharmacists were collected during January 2013 and December 2015. The aspects of service objects, involving drugs, issue categories and the results of feedback were summarized and analyzed.Results:The study summarized 504 work records of clinical pharmacists participating in the drug treatment in orthopedic ward. The rational use of antimicrobial drugs,analgesics and anticoagulants was the key work for clinical pharmacists. Frequently asked questions were drug selection, dosage, treatment plan, drug information, precautions and contraindications, pharmacological effects,adverse drug reactions and drug interactions. The advices of clinical pharmacists were accepted by orthopedists regularly, and the drug treatment regimes were improved with the help of clinical pharmacists. Conclusion:Clinical pharmacists participating in clinical practice can improve rational pharmacotherapy, and also contribute to the cultivation and improvement of self-quality of clinical pharmacist.
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Objective To investigate whether serum miRNA-720 and miRNA-484 can be used as non-invasive biomarkers of colon cancer.Methods Real time-polymerase chain reaction was used to detect the expressions of miRNA-720 and miRNA-484 in serum from 104 colon cancer patients(divided intoⅠ~Ⅱ-stage group andⅢ~Ⅳ-stage group)compared with 60 ad-ditional healthy controls.ROC curve was performed to analyse the diagnostic usefulness of both miRNAs distinguishing be-tween different stages of colon cancer patients.Results Compared with healthy controls,the miRNA-720 was upregulated close to 2 times inⅠ~Ⅱ-stage group (t=1.997,P<0.05),and was upregulated about 3 times inⅢ~Ⅳ-stage group (t=2.133,P<0.05).The miRNA-484 was downregulated almost 2 times inⅠ~Ⅱ-stage group (t=2.585,P<0.05),but was upregulated over 3 times in Ⅲ~Ⅳ-stage group (t=3.416,P<0.01).The area under the ROC curve (AUC)for the diag-nosis of colon cancer were 0.76 (95%CI:0.67~0.86)and 0.79 (95%CI:0.69~0.89)respectively.The combined use of both miRNAs could make the AUC up to 0.87 (95%CI:0.77~0.96).Conclusion Serum miRNA-720 and miRNA-484 can be used as non-invasive biomarkers to diagnose early colon cancer.They can also distinguish between different stages of co-lon cancer patients.
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Objective To investigate the role of c-Jun N-terminal kinase (JNK1/2) signaling pathway in enterovims 71 (EV71) infection.Methods The effects of different concentrations of SP600125 on the activity of human rhabdosarcoma (RD) cells were detected by trypanbalu staining.The levels of VP1 mRNA and protein in EV71-infected RD cells were detected by real time Q-PCR and western blot,respectively.The levels of total and phosphorylated JNK1/2,c-Fos and c-Jun protein were determined by western blot.Last,the effects of.JNK1/2 inhibitor SP600125 on EV71 replication and JNK1/2 signaling pathway were analyzed.Results The results of trypanbalu staining showed that 5 and 10 μmol/L of SP600125 didn't influence on the activity of RD cells (P > 0.05),while 20 μmol/L of SP600125 decreased the survival of RD cells significantly (P < 0.05).Compared with the control,the expression levels of VP1 mRNA and protein in EV71-infected RD cells decreased obviously at 8 hours post-infection (P <0.01).In addition,after RD cells were infected EV71,the levels of phosphorylated JNK1/2,c-Fos and c-Jun increased significantly (P < 0.05).However,the pretreatment of SP600125 decreased the phosphorylation levels of JNK1/2,c-Fos and c-Jun protein obviously (P < 0.05).Conclusion EV71 infection may effectively activate the JNK1/2 signaling pathway in RD cells,which may be related to EV71 replication.
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Objective To evaluate the application of matrix-assisted laser desorption ionization-time-of-flight mass spectrometry (MALDI-TOF MS) technology in the identification of filamentous fungi,and analyze the susceptibility of filamentous fungi to commonly used antibiotics.Methods A total of 100 strains of filamentous fungi were collected and identified rapidly by MALDI-TOF MS.The obtained results were compared with those from microscopic examination.The susceptibility of filamentous fungi was detected by the Etest method.Results Among 100 strains of filamentous fungi identified by MALDI-TOF MS,61 reached to the species level(score≥2.000),36 to the genus level(score between 1.700 and 1.999),and 3 failed to be identified (score < 1.700).There was inconsistent results for one strain of filamentous fungi between MALDI-TOF MS and microscopic examination.The MIC90 of amphotericin B against Epidermophytonfloccosum was 0.19 μg/mL,while that against Aspergillus flavus was above 32 μg/mL.The MIC90 of itraconazole against Trichophyton tonsurans,Microsporum canis and Epidermophytonfloccosum were all below 0.38 μg/mL,while that against Aspergillus niger was above 32 μg/mL.The MIC90 of fluconazol were above 256 μg/mL for most of strains.The MIC90 of voriconazole and caspofungin against Aspergillus fumigatus,Aspergillus flavus,Aspergillus niger,Trichophyton rubrum,Trichophyton tonsurans and Microsporum canis were ≤0.38 μg/mL and ≤ 1 μg/mL,respectively.Conclusion The MALDI-TOF MS technology may be used to identify the filamentous fungi isolated from clinical specimens quickly,accurately and high-throughput.Voriconazole and caspofungin have effective anti-filamentous fungi activity.
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Objective To investigate the clinical values of NT-proBNP in left ventricular enlargement(LVE) and left ventricular dysfunction(LVD) of the patients with essential hypertension(EH) to provide a diagnostic basis for their diagnosis .Methods Plas-ma NT-proBNP concentrations in 120 patients with EH and in 29 normal controls were measured ,then the echocardiography exami-nation was performed to determine the left ventricular ejection fraction ( LVEF) ,left ventricular end-diastolic diameter(LVEDD) , left atrium(LA) and left ventricular systolic diameter(LVSDD) .The correlation between plasma NT-proBNP with LVE and LVD was analyzed .The diagnostic accuracy of NT-proBNP was analyzed by using receiver operating characteristic (ROC) curve .Results There were no statistically significant differences in the aspects of age ,sex and serum creatinine between the EH group and con-trol group ,but plasma NT-proBNP level of the former was significantly higher than that of the latter .The NT-proBNP level in the patients with LVE was significantly higher than that in the patients with normal left ventricle (P<0 .05) .The NT-proBNP level in the LVD patients was significantly higher than that in the patients with normal left ventricular function (P<0 .05) .The plasma NT-p roBNP level was positively correlated with LA ,LVEDD and LVSDD(r=0 .518 ,0 .58 ,0 .48 ,P<0 .01) while negatively crrelated with LVEF(r= -0 .61 ,P<0 .01) .The ROC curve showed that when the NT-proBNP was set at 380 pg/mL ,the sensitivity and specificity of NT-proBNP for diagnosing LVE were 80 .6% and 72 .4% ;which for diagnosing LVD were 80 .8% and 77 .4% ,re-spectively .Conclusion NT-proBNP is closely correlated with multiple ultrasonic indicators reflecting the left ventricular function and its level can reliably reflect the left ventricular contraction function ,which can serve as the marker for screening LVE and LVD in the patients with EH .