BACKGROUND:At present,osteoarthritis has become a major disease affecting the quality of life of the elderly,and the therapeutic effect is poor,often focusing on preventing the disease process,and the pathogenesis of osteoarthritis is still not fully understood.Bioinformatics analysis was carried out to explore the main pathogenesis of osteoarthritis and related mechanisms of gene coding regulation. OBJECTIVE:To screen core differential genes with a major role in osteoarthritis by gene expression profiling. METHODS:Datasets were downloaded from the Gene Expression Omnibus(GEO):GSE114007,GSE117999,and GSE129147.Differential genes in the GSE114007 and GSE117999 data collections were screened using R software,performing differential genes to weighted gene co-expression network analysis.The module genes most relevant to osteoarthritis were selected to perform protein interaction analysis.Candidate core genes were selected using the cytocape software.The candidate core genes were subsequently subjected to least absolute shrinkage and selection operator regression and COX analysis to identify the core genes with a key role in osteoarthritis.The accuracy of the core genes was validated using an external dataset,GSE129147. RESULTS AND CONCLUSION:(1)A total of 477 differential genes were identified,265 differential genes associated with osteoarthritis were obtained by weighted gene co-expression network analysis,and 8 candidate core genes were identified.The least absolute shrinkage and selection operator regression analysis finally yielded a differential gene ASPM with core value that was externally validated.(2)It is concluded that abnormal gene ASPM expression screened by bioinformatics plays a key central role in osteoarthritis.

As a member of class I histone deacetylase (HDACs), HDAC8 is an important anticancer drug target. Based on our previously developed pharmacophore model for the HDAC8 inhibitor, we designed and synthesized 13 quinoline acid derivatives as new HDAC8 inhibitors. Among them, the compound SDFZ-E2 and SDFZ-E3 exhibited good HDAC8 inhibitory activities and isoform selectivity. In cell experiments, the target compounds SDFZ-E2 and SDFZ-E3 showed better antiproliferation activities than the known HDAC8 selective inhibitor PCI-34051. In addition, the proposed binding mode of SDFZ-E2 was investigated using molecular docking and molecular dynamics simulation. This work is a new attempt to develop HDAC8 selective inhibitor using quinoline as the scaffold, and the active compounds could serve as lead compounds for further structural optimization.

OBJECTIVES: To investigate the clinical features of juvenile myelomonocytic leukemia (JMML) and their association with prognosis. METHODS: Clinical and prognosis data were collected from the children with JMML who were admitted from January 2008 to December 2016, and the influencing factors for prognosis were analyzed. RESULTS: A total of 63 children with JMML were included, with a median age of onset of 25 months and a male/female ratio of 3.2∶1. JMML genetic testing was performed for 54 children, and PTPN11 mutation was the most common mutation and was observed in 23 children (43%), among whom 19 had PTPN11 mutation alone and 4 had compound PTPN11 mutation, followed by NRAS mutation observed in 14 children (26%), among whom 12 had NRAS mutation alone and 2 had compound NRAS mutation. The 5-year overall survival (OS) rate was only 22%±10% in these children with JMML. Of the 63 children, 13 (21%) underwent hematopoietic stem cell transplantation (HSCT). The HSCT group had a significantly higher 5-year OS rate than the non-HSCT group (46%±14% vs 29%±7%, P<0.05). There was no significant difference in the 5-year OS rate between the children without PTPN11 gene mutation and those with PTPN11 gene mutation (30%±14% vs 27%±10%, P>0.05). The Cox proportional-hazards regression model analysis showed that platelet count <40×10⁹/L at diagnosis was an influencing factor for 5-year OS rate in children with JMML (P<0.05). CONCLUSIONS The PTPN11 gene was the most common mutant gene in JMML. Platelet count at diagnosis is associated with the prognosis in children with JMML. HSCT can improve the prognosis of children with JMML.
Child ; Humans ; Male ; Female ; Child, Preschool ; Leukemia, Myelomonocytic, Juvenile/therapy* ; Prognosis ; Genetic Testing ; Mutation ; Hematopoietic Stem Cell Transplantation

OBJECTIVE: To develop and validate a nomogram for predicting outcomes of patients with gastric neuroendocrine neoplasms (G-NENs). METHODS: We retrospectively collected the clinical data from 490 patients with the diagnosis of G-NEN at our medical center from 2000 to 2021. Log-rank test was used to analyze the overall survival (OS) of the patients. The independent risk factors affecting the prognosis of G-NEN were identified by Cox regression analysis to construct the prognostic nomogram, whose performance was evaluated using the C-index, receiver-operating characteristic (ROC) curve, area under the ROC curve (AUC), calibration curve, DCA, and AUDC. RESULTS: Among the 490 G-NEN patients (mean age of 58.6±10.92 years, including 346 male and 144 female patients), 130 (26.5%) had NET G1, 54 (11.0%) had NET G2, 206 (42.0%) had NEC, and 100 (20.5%) had MiNEN. None of the patients had NET G3. The numbers of patients in stage Ⅰ-Ⅳ were 222 (45.3%), 75 (15.3%), 130 (26.5%), and 63 (12.9%), respectively. Univariate and multivariate analyses identified age, pathological grade, tumor location, depth of invasion, lymph node metastasis, distant metastasis, and F-NLR as independent risk factors affecting the survival of the patients (P < 0.05). The C-index of the prognostic nomogram was 0.829 (95% CI: 0.800-0.858), and its AUC for predicting 1-, 3- and 5-year OS were 0.883, 0.895 and 0.944, respectively. The calibration curve confirmed a good consistency between the model prediction results and the actual observations. For predicting 1-year, 3-year and 5-year OS, the TNM staging system and the nomogram had AUC of 0.033 vs 0.0218, 0.191 vs 0.148, and 0.248 vs 0.197, respectively, suggesting higher net benefit and better clinical utility of the nomogram. CONCLUSION The prognostic nomogram established in this study has good predictive performance and clinical value to facilitate prognostic evaluation of individual patients with G-NEN.
Humans ; Male ; Female ; Middle Aged ; Aged ; Nomograms ; Retrospective Studies ; Prognosis ; Neoplasm Staging ; Stomach Neoplasms/pathology*

OBJECTIVE: Huangqi Decoction (HQD), a classical traditional Chinese medicine formula, has been used as a valid treatment for alleviating liver fibrosis; however, the underlying molecular mechanism is still unknown. Although our previous studies showed that microRNA-663a (miR-663a) suppresses the proliferation and activation of hepatic stellate cells (HSCs) and the transforming growth factor-β/small mothers against decapentaplegic (TGF-β/Smad) pathway, whether long noncoding RNAs (lncRNAs) are involved in HSC activation via the miR-663a/TGF-β/Smad signaling pathway has not yet reported. The present study aimed to investigate the roles of lncRNA lnc-C18orf26-1 in the activation of HSCs and the mechanism by which HQD inhibits hepatic fibrosis. METHODS: The expression levels of lnc-C18orf26-1, miR-663a and related genes were measured by quantitative reverse transcription-polymerase chain reaction. HSCs were transfected with the miR-663a mimic or inhibitor and lnc-C18orf26-1 small interfering RNAs. The water-soluble tetrazolium salt-1 assay was used to assess the proliferation rate of HSCs. Changes in lncRNA expression were evaluated in miR-663a-overexpressing HSCs by using microarray to identify miR-663a-regulated lncRNAs. RNA hybrid was used to predict the potential miR-663a binding sites on lncRNAs. Luciferase reporter assays further confirmed the interaction between miR-663a and the lncRNA. The expression levels of collagen α-2(I) chain (COL1A2), α-smooth muscle actin (α-SMA) and TGF-β/Smad signaling pathway-related proteins were determined using Western blotting. RESULTS: Lnc-C18orf26-1 was upregulated in TGF-β1-activated HSCs and competitively bound to miR-663a. Knockdown of lnc-C18orf26-1 inhibited HSC proliferation and activation, downregulated TGF-β1-stimulated α-SMA and COL1A2 expression, and inhibited the TGF-β1/Smad signaling pathway. HQD suppressed the proliferation and activation of HSCs. HQD increased miR-663a expression and decreased lnc-C18orf26-1 expression in HSCs. Further studies showed that HQD inhibited the expression of COL1A2, α-SMA, TGF-β1, TGF-β type I receptor (TGF-βRI) and phosphorylated Smad2 (p-Smad2) in HSCs, and these effects were reversed by miR-663a inhibitor treatment. CONCLUSION Our study identified lnc-C18orf26-1 and miR-663a as promising therapeutic targets for hepatic fibrosis. HQD inhibits HSC proliferation and activation at least partially by regulating the lnc-C18orf26-1/miR-663a/TGF-β1/TGF-βRI/p-Smad2 axis.
Humans ; Transforming Growth Factor beta/pharmacology* ; Transforming Growth Factor beta1/metabolism* ; RNA, Long Noncoding/pharmacology* ; Drugs, Chinese Herbal/pharmacology* ; MicroRNAs/genetics* ; Hepatic Stellate Cells/pathology* ; Liver Cirrhosis/metabolism* ; Cell Proliferation ; Transforming Growth Factors/pharmacology*

CRISPR/Cas(the clustered regularly interspaced short palindromic repeats-CRISPR associated)system exists in most bacteria and all archaea. It is an important strategy for bacteria and archaea to resist foreign nucleic acid invasion and use for self-defense. The CRISPR/Cas system is a simple, fast, and specific diagnostic tool, which is widely used in agriculture, industry, animal husbandry, and medicine. This article mainly introduces and discusses recently advantages and limitations of biosensors combining CRISPR/Cas system with fluorescence, visualization and surface enhanced raman related technologies, as well as future research directions.
Animals ; CRISPR-Cas Systems ; Bacteria/genetics* ; Archaea

To understand the clinical characteristics of Staphylococcus aureus bloodstream infection and the main risk factors affecting clinical prognosis, providing a reference for clinical prevention and control of Staphylococcus aureus bloodstream infection. In this study, the clinical data of 152 patients with Staphylococcus aureus bloodstream infection admitted to Guangdong Provincial People's Hospital from January 2019 to December 2021 were retrospectively analyzed by reviewing the electronic medical record system, including underlying diseases, clinical characteristics, risk factors, and bacterial resistance. Statistical methods such as Chi-Squared Test and t Test were used to analyze the related risk factors that may affect the clinical characteristics and prognosis of patients with Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection, then the variables with P<0.05 in univariate analysis were included in the multivariate logistic regression model to analyze the independent risk factors of poor prognosis. The results showed among 152 patients with Staphylococcus aureus bloodstream infection, 50 patients (32.89%) were infected with MRSA. In comparison, 102 patients (67.11%) were infected with methicillin-sensitive Staphylococcus aureus (MSSA). Except for rifampicin, the resistance rate of MRSA to commonly used antibiotics was all higher than that of MSSA, and the difference was statistically significant (Chi-square values were 8.272, 11.972, 4.998, 4.776, respectively;all P-values are less than 0.05). Strains resistant to vancomycin, linezolid, and quinupristin/dalfopristin were not found. In the MRSA group, indwelling catheter and drainage tube, carbapenems, and β-lactamase inhibitor treatment were significantly higher than the MSSA group. The difference was statistically significant (P<0.05). The incidence of poor prognosis of bloodstream infection in the MRSA group was higher than that in the MSSA group (34.00% vs 13.73%), and the difference was statistically significant (χ²=8.495, P<0.05). No independent risk factors associated with poor prognosis were found in the included patients with MRSA bloodstream infection.Multivariate Logistic regression model analysis showed that solid malignant tumors (OR=13.576, 95%CI: 3.352-54.977, P<0.05), mechanical ventilation (OR=7.468, 95%CI: 1.398-39.884, P<0.05) were the most important independent risk factors for poor prognosis in patients with Staphylococcus aureus bloodstream infection. In summary, the poor prognosis rate of MRSA bloodstream infection is higher than that of MSSA. The clinical evaluation of related risk factors should be strengthened, targeted prevention and control interventions should be taken to improve the prognosis of patients with Staphylococcus aureus bloodstream infection, and the use of antibiotics should be rational and standardized, to control bacterial infection and drug resistance effectively .
Humans ; Methicillin-Resistant Staphylococcus aureus ; Staphylococcus aureus ; Retrospective Studies ; Prognosis ; Staphylococcal Infections/microbiology* ; Anti-Bacterial Agents/pharmacology* ; Methicillin/therapeutic use* ; Sepsis

Myelodysplastic syndromes (MDS) are a subset of myeloid malignancies defined by clonality of immature hematopoietic stem cells that leads to faulty blood cell development. These syndromes can lead to an increased risk of infection and may transform into acute myeloid leukemia, making it critical to determine effective treatments for the condition. While hypomethylating agents such as azacitidine and decitabine, as well as stem cell transplants, have been delineated as favored treatments for MDS, not all patients are physiologically receptive to these treatments. However, black raspberries (BRBs) have been shown to exert hypomethylating effects in various malignancies, with minimal adverse effects and thus a broader range of potential candidacies. This study aimed to investigate the potential of BRBs to exert such effects on MDS using Addition of Sex Combs Like/Tet Methylcytosine Dioxygenase 2 (Asxl1/Tet2) double knockout mice (Vav-cre Asxl1fl/fl Tet2fl/fl ), which typically manifest symptoms around 25 weeks of age, mirroring genetic mutations found in humans with MDS. Following a 12-week dietary supplementation of Vav-cre Asxl1fl/fl Tet2fl/fl mice with 5% BRBs, we observed both hyper- and hypomethylation at multiple transcription start sites and intragenic locations linked to critical pathways, including hematopoiesis. This methylation profile may have implications for delaying the onset of MDS, prompting a need for in-depth investigation. Our results emphasize the importance of exploring whether an extended BRB intervention can effectively alter MDS risk and elucidate the relationship between BRB-induced methylation changes, thus further unlocking the potential benefits of BRBs for MDS patients.

Objective: To investigate the application value of computed tomography (CT) examination of lymph node short diameter in evaluating cardia-left gastric lymph node metastasis in thoracic esophageal squamous cell carcinoma (ESCC). Methods: A total of 477 patients with primary thoracic ESCC who underwent surgical treatment in the Affiliated Cancer Hospital of Zhengzhou University from January 2013 to December 2017 were collected. All of them underwent McKeown esophagectomy plus complete two-field or three-field lymph node dissection. Picture archiving and communication system were used to measure the largest cardia-left gastric lymph node short diameter in preoperative CT images. The postoperative pathological diagnosis results of cardia-left gastric lymph node were used as the gold standard. Receiver operating characteristic (ROC) curve was used to evaluate the efficacy of CT lymph node short diameter in detecting the metastasis of cardia-left gastric lymph node in thoracic ESCC, and determine the optimal cut-off value. Results: The median short diameter of the largest cardia-left gastric lymph node was 4.1 mm in 477 patients, and the largest cardia-left gastric lymph node short diameter was less than 3 mm in 155 cases (32.5%). Sixty-eight patients had cardia-left gastric lymph node metastases, of which 38 had paracardial node metastases and 41 had left gastric node metastases. The lymph node ratios of paracardial node and left gastric node were 4.0% (60/1 511) and 3.3% (62/1 887), respectively. ROC curve analysis showed that the area under the curve of CT lymph node short diameter for evaluating cardia-left gastric lymph node metastasis was 0.941 (95% CI: 0.904-0.977; P<0.05). The optimal cut-off value of CT examination of the cardia-left gastric lymph node short diameter was 6 mm, and the corresponding sensitivity, specificity and accuracy were 85.3%, 91.7%, and 90.8%, respectively. Conclusion: CT examination of lymph node short diameter can be a good evaluation of cardia-left gastric lymph node metastasis in thoracic ESCC, and the optimal cut-off value is 6 mm.
Humans ; Esophageal Squamous Cell Carcinoma/pathology* ; Cardia/surgery* ; Esophageal Neoplasms/pathology* ; Lymphatic Metastasis/pathology* ; Lymph Nodes/pathology* ; Lymph Node Excision ; Tomography, X-Ray Computed/methods* ; Esophagectomy/methods* ; Retrospective Studies

Objective: To investigate the application value of computed tomography (CT) examination of lymph node short diameter in evaluating cardia-left gastric lymph node metastasis in thoracic esophageal squamous cell carcinoma (ESCC). Methods: A total of 477 patients with primary thoracic ESCC who underwent surgical treatment in the Affiliated Cancer Hospital of Zhengzhou University from January 2013 to December 2017 were collected. All of them underwent McKeown esophagectomy plus complete two-field or three-field lymph node dissection. Picture archiving and communication system were used to measure the largest cardia-left gastric lymph node short diameter in preoperative CT images. The postoperative pathological diagnosis results of cardia-left gastric lymph node were used as the gold standard. Receiver operating characteristic (ROC) curve was used to evaluate the efficacy of CT lymph node short diameter in detecting the metastasis of cardia-left gastric lymph node in thoracic ESCC, and determine the optimal cut-off value. Results: The median short diameter of the largest cardia-left gastric lymph node was 4.1 mm in 477 patients, and the largest cardia-left gastric lymph node short diameter was less than 3 mm in 155 cases (32.5%). Sixty-eight patients had cardia-left gastric lymph node metastases, of which 38 had paracardial node metastases and 41 had left gastric node metastases. The lymph node ratios of paracardial node and left gastric node were 4.0% (60/1 511) and 3.3% (62/1 887), respectively. ROC curve analysis showed that the area under the curve of CT lymph node short diameter for evaluating cardia-left gastric lymph node metastasis was 0.941 (95% CI: 0.904-0.977; P<0.05). The optimal cut-off value of CT examination of the cardia-left gastric lymph node short diameter was 6 mm, and the corresponding sensitivity, specificity and accuracy were 85.3%, 91.7%, and 90.8%, respectively. Conclusion: CT examination of lymph node short diameter can be a good evaluation of cardia-left gastric lymph node metastasis in thoracic ESCC, and the optimal cut-off value is 6 mm.
Humans ; Esophageal Squamous Cell Carcinoma/pathology* ; Cardia/surgery* ; Esophageal Neoplasms/pathology* ; Lymphatic Metastasis/pathology* ; Lymph Nodes/pathology* ; Lymph Node Excision ; Tomography, X-Ray Computed/methods* ; Esophagectomy/methods* ; Retrospective Studies