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.

Objective:To investigate the effect of modified percutaneous closure in the treatment of ventricular septal rupture.Methods:This study is a retrospective cohort study. Forty-four patients with ventricular septal rupture who underwent percutaneous closure at the Fuwai Central China Cardiovascular Hospital from December 2017 to October 2023 were included. According to the closure method, patients were divided into the modified group (11 cases) and the traditional group (33 cases). Surgical success was defined as successful placement of the occluder. The operation time, X-ray intake, sheath bending rate, incidence of ventricular fibrillation and pericardial tamponade, and postoperative residual shunt were compared between the two groups.Results:The age of the patients was (75.0±5.7) years, with 20 (45%) males. There were 3 cases of operation failure in the traditional group, while all patients in the modified group were successfully occluded. The procedure time in the modified group was shorter than that in the traditional group (40 (35, 45) min vs. 60 (50, 65)min, P<0.001); X-ray dose intake was lower ((442.43±73.26)mGy vs. (784.45±247.78)mGy, P<0.001). There was no occurrence of sheath bending in the modified group, while the incidence of sheath bending in the traditional surgery group was 46% (15/33), and the difference was statistically significant ( P=0.017). Intraoperative ventricular fibrillation and pericardial tamponade occurred in 7 cases (21%) and 2 cases (6%) in the traditional group respectively, while none occurred in the modified group, but the differences between the groups were not statistically significant (both P>0.05). There was no significant difference in residual shunt between the two groups (3.6 (2.5, 4.3) mm vs. 4.0 (3.5, 4.5) mm, P=0.506). Conclusion:The procedure of modified ventricular septal rupture closure is more simplified, with a lower incidence ofventricular fibrillation and pericardial tamponade.

Objective:To investigate the efficacy of decitabine combined with preexcitation regimen in the treatment of newly diagnosed acute myeloid leukemia(AML)patients who have not been relieved by the first standard induction chemotherapy and its influence on the relative content of regulatory T lymphocytes(Tregs).Methods:The clinical data of 102 newly diagnosed AML patients(except acute promyelocytic leukemia)who did not relieve after initial standard induction chemotherapy in Shaanxi Provincial People's Hospital from March 2013 to March 2019 were retrospectively analyzed.Fifty-one patients who accepted pre-excitation regimen were divided into regular group,while another 51 patients treated with decitabine combined with pre-excitation regimen were divided into combination group.The efficacy,incidence of toxic and side effects,Core Scale of Quality of Life(QLQ-C30)score before and after treatment,T lymphocyte subsets(CD3+,CD4+,CD4+/CD8+,Tregs)and 3-year overall survival(OS)rate were compared between the two groups.Results:The total effective rate of combination group was 80.39％,which was significantly higher than 62.75％of regular group(P＜0.05).After treatment,the QLQ-C30 score of combination group was 60.27 ±6.96,which was significantly lower than 65.73±7.96 of regular group(P＜0.001).There was no statistical difference in the incidence of toxic and side effects between the two groups(P＞0.05).After treatment,the levels of CD3+,CD4+,CD4+/CD8+in the combination group were higher than those in the regular group(all P＜0.001),while Treg was lower(P＜0.001).The 3-year OS rate in the combination group was 72.55％,which was significantly higher than 52.94％in the regular group(P＜0.001).Conclusion:Decitabine combined with preexcitation regimen has a significant effect on AML patients who have not been alleviated by standard induction chemotherapy in the first course of treatment.It can reduce anti-tumor immune suppression and improve immune function by regulating the relative content of Tregs,thus prolongs survival time and improves life quality of patients without increasing adverse reactions.

Objective: To explore the clinicopathological features, treatment strategy and to analysis of prognosis-related risk factors of gastric neuroendocrine neoplasms(G-NEN). Methods: In this study, a retrospective observational study method was used to collect the clinicopathological data of patients diagnosed with G-NEN by pathological examination in the First Medical Center of PLA General Hospital from January 2000 to December 2021. The basic information of the patients, tumor pathological characteristics, and treatment methods were entered, and the treatment information and survival data after discharge were followed up and recorded. The Kaplan-Meier method was used to construct survival curves, and the log-rank test to analyze the differences in survival between groups. Cox Regression model analysis of risk factors affecting the prognosis of G-NEN patients. Results: Among the 501 cases confirmed as G-NEN, 355 were male and 146 were female, and their median age was 59 years. The cohort comprised 130 patients (25.9%) of neuroendocrine tumor (NET) G1, 54 (10.8%) of NET G2, 225 (42.9%) of neuroendocrine carcinoma (NEC), and 102 cases (20.4%) of mixed neuroendocrine-non-neuroendocrine(MiNEN). Patients NET G1 and NET G2 were mainly treated by endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR). The main treatment for patients with NEC/MiNEN was the same as that for gastric malignancies, namely radical gastrectomy+lymph node dissection supplemented with postoperative chemotherapy. There were significant differences in sex, age, maximum tumor diameter, tumor morphology, tumor numbers, tumor location, depth of invasion, lymph node metastasis, distant metastasis, TNM staging and expression of immunohistological markers Syn and CgA among NET, NEC, and MiNEN patients (all P<0.05). Further for NET subgroup analysis, there were significant differences between NET G1 and NET G2 in the maximum tumor diameter, tumor shape and depth of invasion(all P<0.05). 490 patients (490/501, 97.8%) were followed up with a median of 31.2 months. 163 patients had a death during follow-up (NET G1 2, NET G2 1, NEC 114, MiNEN 46). For NET G1, NET G2, NEC and MiNEN patients,the 1-year overall survival rates were 100%, 100%, 80.1% and 86.2%, respectively; the 3-year survival rates were 98.9%, 100%, 43.5% and 55.1%, respectively. The differences were statistically significant (P<0.001). Univariate analysis showed that gender, age, smoking history, alcohol history, tumor pathological grade, tumor morphology, tumor location, tumor size, lymph node metastasis, distant metastasis, and TNM stage were associated with the prognosis of G-NEN patients (all P<0.05). Multivariate analysis showed that age ≥60 years, pathological grade of NEC and MiNEN, distant metastasis, and TNM stage III-IV were independent factors influencing the survival of G-NEN patients (all P<0.05). 63 cases were stage IV at initial diagnosis. 32 of these were treated with surgery and 31 with palliative chemotherapy. Stage IV subgroup analysis showed that the 1-year survival rates were 68.1% and 46.2% in the surgical treatment and palliative chemotherapy groups, respectively, and the 3-year survival rates were 20.9% and 10.3%, respectively; the differences were statistically significant (P=0.016). Conclusions: G-NEN is a heterogeneous group of tumors. Different pathological grades of G-NEN have different clinicopathological features and prognosis. Factors such as age ≥ 60 years old, pathological grade of NEC/MiNEN, distant metastasis, stage III, IV mostly indicate poor prognosis of patients. Therefore, we should improve the ability of early diagnosis and treatment, and pay more attention to patients with advanced age and NEC/MiNEN. Although this study concluded that surgery improves the prognosis of advanced patients more than palliative chemotherapy, the value of surgical treatment for patients with stage IV G-NEN remains controversial.
Humans ; Male ; Female ; Middle Aged ; Stomach Neoplasms/pathology* ; Lymphatic Metastasis ; Prognosis ; Neuroendocrine Tumors/pathology* ; Carcinoma, Neuroendocrine/therapy* ; Neoplasm Staging ; Retrospective Studies

italic>Tussilago farfara L. is a perennial herb of Tussilago genus in the Compositae family. Its dried buds and leaves have good biological activities and have a long history of medicinal use in China and Europe. In this paper, we investigated the whole chloroplast genome characteristics, sequence duplication, structural variation and phylogeny of the Tussilago farfara L. After sequencing the Tussilago farfara L. chloroplast genome using Illumination technology, the complete Tussilago farfara L. chloroplast genome was further obtained by assembly and annotation, followed by a series of inverted repeat-large single copy/small single copy region contraction and expansion analysis, genome sequence variation, etc. The sequences of 13 homologous plants downloaded from NCBI were used to construct a neighbor-joining phylogenetic tree. The results showed that the total GC content of the chloroplast genome was 37.4% and the length was 150 300 bp; 125 genes were annotated, including 82 protein-coding genes, 35 tRNAs and 8 rRNAs; 148 (simple sequence repeats, SSR) loci were detected, and the relative synonymous codon usage showed that 31 codons out of 64 codons had a usage of >1. In the phylogenetic analysis, the chloroplast genomes of the seven species of Asteraceae, including the Yulin Tussilago farfara L., were highly conserved, and the sequence variation of the (large single-copy, LSC) and (small single-copy, SSC) regions was higher than that of the (inverted repeat, IR) region. This is in general agreement with the reported phylogeny of Yulin Tussilago farfara L. In this study, we obtained a high quality chloroplast genome and analyzed its genome characteristics, codon preference, SSR characteristics, SC/IR boundary, sequence variation and phylogeny, which can provide a basis for species identification, genetic diversity analysis and resource development of this medicinal plant.

OBJECTIVE: Arsenic (As) and fluoride (F) are two of the most common elements contaminating groundwater resources. A growing number of studies have found that As and F can cause neurotoxicity in infants and children, leading to cognitive, learning, and memory impairments. However, early biomarkers of learning and memory impairment induced by As and/or F remain unclear. In the present study, the mechanisms by which As and/or F cause learning memory impairment are explored at the multi-omics level (microbiome and metabolome). METHODS: We stablished an SD rats model exposed to arsenic and/or fluoride from intrauterine to adult period. RESULTS: Arsenic and/fluoride exposed groups showed reduced neurobehavioral performance and lesions in the hippocampal CA1 region. 16S rRNA gene sequencing revealed that As and/or F exposure significantly altered the composition and diversity of the gut microbiome，featuring the Lachnospiraceae_NK4A136_group, Ruminococcus_1, Prevotellaceae_NK3B31_group, [Eubacterium]_xylanophilum_group. Metabolome analysis showed that As and/or F-induced learning and memory impairment may be related to tryptophan, lipoic acid, glutamate, gamma-aminobutyric acidergic (GABAergic) synapse, and arachidonic acid (AA) metabolism. The gut microbiota, metabolites, and learning memory indicators were significantly correlated. CONCLUSION Learning memory impairment triggered by As and/or F exposure may be mediated by different gut microbes and their associated metabolites.
Rats ; Animals ; Arsenic/toxicity* ; Fluorides ; RNA, Ribosomal, 16S/genetics* ; Rats, Sprague-Dawley ; Metabolome ; Microbiota

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: To describe the gene mutation profile of newly diagnosed pediatric B-acute lymphoblastic leukemia (B-ALL) and analyze its effect on minimal residual disease (MRD). Methods: A total of 506 newly diagnosed B-ALL children treated in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences from September 2018 to July 2021 were enrolled in this retrospective cohort study. The enrolled children were divided into MRD ≥1.00% group and <1.00% group according to MRD results on the 19th day since chemotherapy, and MRD ≥0.01% group and <0.01% group according to MRD results on the 46th day. Clinical characteristics and gene mutations of two groups were compared. Comparisons between groups were performed with chi-square test or Fisher's exact test. Independent risk factors of MRD results on the 19th day and the 46th day were analyzed by Logistic regression model. Results: Among all 506 patients, there were 318 males and 188 females. On the 19th day, there were 114 patients in the MRD ≥1.00% group and 392 patients in the MRD <1.00% group. On the 46th day, there were 76 patients in the MRD ≥0.01% group and 430 patients in the MRD <0.01% group. A total of 187 gene mutations were detected in 487 (96.2%) of 506 children. The most common gene mutations were signal transduction-related KRAS gene mutations in 111 cases (22.8%) and NRAS gene mutations in 99 cases (20.3%). Multivariate analysis showed that PTPN11 (OR=1.92, 95%CI 1.00-3.63), KMT2A (OR=3.51, 95%CI 1.07-11.50) gene mutations and TEL-AML1 (OR=0.48, 95%CI 0.27-0.87), BCR-ABL1 (OR=0.27, 95%CI 0.08-0.92) fusion genes and age >10 years (OR=1.91, 95%CI 1.12-3.24) were independent influencing factors for MRD ≥1.00% on the 19th day. BCORL1 (OR=2.96, 95%CI 1.18-7.44), JAK2 (OR=2.99, 95%CI 1.07-8.42) and JAK3 (OR=4.83, 95%CI 1.50-15.60) gene mutations and TEL-AML1 (OR=0.43, 95%CI 0.21-0.87) fusion gene were independent influencing factors for MRD ≥0.01% on the 46th day. Conclusions: Children with B-ALL are prone to genetic mutations, with abnormalities in the RAS signaling pathway being the most common. Signal transduction related PTPN11, JAK2 and JAK3 gene mutations, epigenetic related KMT2A gene mutation and transcription factor related BCORL1 gene mutation are independent risk factors for MRD.
Child ; Female ; Male ; Humans ; High-Throughput Nucleotide Sequencing ; Neoplasm, Residual/genetics* ; Retrospective Studies ; Genomics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma

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 risk factors for early-stage complications among liver transplant recipients, and to establish and validate a risk prediction model for early-stage complications after transplantation. Methods A retrospective analysis was performed for the clinical data of 234 patients who underwent orthotopic liver transplantation in Department of Liver Transplantation, Tianjin First Central Hospital, from January 2016 to December 2018. According to the presence or absence of Clavien-Dindo grade ≥Ⅲ complications after liver transplantation, the patients were divided into complication group with 97 patients and non-complication group with 137 patients. The two groups were compared in terms of the indices including age, sex, body mass index (BMI), blood type, psoas muscle thickness/height (PMTH), Controlling Nutritional Status (CONUT) score, Model for End-Stage Liver Disease (MELD) score, total serum bilirubin, serum creatinine, international normalized ratio of prothrombin time, blood urea nitrogen, hemoglobin, white blood cell count, platelet count, amount of intraoperative red blood cell transfusion, amount of frozen plasma transfusion, blood loss, anhepatic phase, time of operation, donor age, donor BMI, cold ischemia time of donor liver, and warm ischemia time of donor liver. The independent samples t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between two groups. Univariate analysis and the binary logistic regression analysis were used to investigate the risk factors for early-stage complications after liver transplantation, and a risk prediction model for complications after liver transplantation was established based on the method for establishing a scoring system using the logistic model provided by Framingham Research Center. Internal validation of the model was performed by C-index, receiver operating characteristic (ROC) curve, calibration curve, and the Hosmer-Lemeshow test, and the decision curve was used to evaluate the clinical applicability of the model. The Kaplan-Meier method was used to compare the incidence rate of early-stage complications after liver transplantation between the patients with different risk scores. Results Compared with the non-complication group, the complication group had significantly higher MELD score, proportion of patients with low PMTH, total serum bilirubin, serum creatinine, blood urea nitrogen, CONUT score, amount of intraoperative red blood cell transfusion, and amount of frozen plasma transfusion, as well as a significantly lower level of hemoglobin (all P < 0.1). The multivariate binary logistic regression analysis showed that MELD score (odds ratio [ OR ]=1.104, 95% confidence interval [ CI ]: 1.057-1.154, P < 0.05), PMTH ( OR =2.858, 95% CI : 1.451-5.626, P < 0.05), and CONUT score ( OR =1.481, 95% CI : 1.287-1.703, P < 0.05) were independent risk factors for grade ≥Ⅲ complications in the early stage after liver transplantation. MELD score, PMTH, and CONUT score were included in a predictive model, and this model had the highest score of 24 points, a C-index of 0.828, an area under the ROC curve of 0.812( P < 0.001), a sensitivity of 0.792, and a specificity of 0.751, suggesting that this predictive model had good discriminatory ability. The calibration curve of this model was close to the reference curve, and the Hosmer-Lemeshow test obtained a chi-square value of 8.528( P =0.382), suggesting that this predictive model had a high degree of fitting. The decision curve showed that most patients were able to benefit from the predictive model and achieved a high net benefit rate, suggesting that this predictive model had good clinical applicability. The score of 11 was selected as the cut-off value according to the optimal Youden index of 0.507, and the patients were divided into low-risk (< 8 points) group with 55 patients, moderate-risk (8-10 points) group with 63 patients, high-risk (11-14 points) group with 67 patients, and extremely high-risk (≥15 points) group with 49 patients. These four groups had a 90-day cumulative incidence rate of early-stage postoperative complications of 3.6%, 28.6%, 59.7%, and 75.5%, respectively, and the incidence rate of complications increased with the increase in risk score ( P < 0.001). Conclusion MELD score, PMTH, and CONUT score are independent risk factors for early-stage complications among liver transplant recipients, and the risk prediction model established based on these factors has a high predictive value in high-risk patients.