Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 53
Filter
1.
JAMA Netw Open ; 7(5): e2413708, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38809553

ABSTRACT

Importance: Helicobacter pylori treatment and nutrition supplementation may protect against gastric cancer (GC), but whether the beneficial effects only apply to potential genetic subgroups and whether high genetic risk may be counteracted by these chemoprevention strategies remains unknown. Objective: To examine genetic variants associated with the progression of gastric lesions and GC risk and to assess the benefits of H pylori treatment and nutrition supplementation by levels of genetic risk. Design, Setting, and Participants: This cohort study used follow-up data of the Shandong Intervention Trial (SIT, 1989-2022) and China Kadoorie Biobank (CKB, 2004-2018) in China. Based on the SIT, a longitudinal genome-wide association study was conducted to identify genetic variants for gastric lesion progression. Significant variants were examined for incident GC in a randomly sampled set of CKB participants (set 1). Polygenic risk scores (PRSs) combining independent variants were assessed for GC risk in the remaining CKB participants (set 2) and in an independent case-control study in Linqu. Exposures: H pylori treatment and nutrition supplementation. Main Outcomes and Measures: Primary outcomes were the progression of gastric lesions (in SIT only) and the risk of GC. The associations of H pylori treatment and nutrition supplementation with GC were evaluated among SIT participants with different levels of genetic risk. Results: Our analyses included 2816 participants (mean [SD] age, 46.95 [9.12] years; 1429 [50.75%] women) in SIT and 100 228 participants (mean [SD] age, 53.69 [11.00] years; 57 357 [57.23%] women) in CKB, with 147 GC cases in SIT and 825 GC cases in CKB identified during follow-up. A PRS integrating 12 genomic loci associated with gastric lesion progression and incident GC risk was derived, which was associated with GC risk in CKB (highest vs lowest decile of PRS: hazard ratio [HR], 2.54; 95% CI, 1.80-3.57) and further validated in the analysis of 702 case participants and 692 control participants (mean [SD] age, 54.54 [7.66] years; 527 [37.80%] women; odds ratio, 1.83; 95% CI, 1.11-3.05). H pylori treatment was associated with reduced GC risk only for individuals with high genetic risk (top 25% of PRS: HR, 0.45; 95% CI, 0.25-0.82) but not for those with low genetic risk (HR, 0.81; 95% CI, 0.50-1.34; P for interaction = .03). Such effect modification was not found for vitamin (P for interaction = .93) or garlic (P for interaction = .41) supplementation. Conclusions and Relevance: The findings of this cohort study indicate that a high genetic risk of GC may be counteracted by H pylori treatment, suggesting primary prevention could be tailored to genetic risk for more effective prevention.


Subject(s)
Genetic Predisposition to Disease , Helicobacter Infections , Helicobacter pylori , Stomach Neoplasms , Humans , Stomach Neoplasms/genetics , Stomach Neoplasms/epidemiology , Female , Male , Middle Aged , Helicobacter Infections/drug therapy , Helicobacter Infections/complications , China/epidemiology , Genome-Wide Association Study , Case-Control Studies , Adult , Risk Factors , Dietary Supplements , Cohort Studies , Aged , Anti-Bacterial Agents/therapeutic use
2.
Pediatr Hematol Oncol ; 41(1): 1-14, 2024.
Article in English | MEDLINE | ID: mdl-37452625

ABSTRACT

Severe sepsis and septic shock are life-threatening for pediatric hematology and oncology patient receiving chemotherapy. Th1/Th2 cytokines, C-reactive protein (CRP), and procalcitonin (PCT) are all thought to be associated with disease severity. The aim of this study was to prospectively verify the utility of Th1/Th2 cytokines and compare them with PCT and CRP in the prediction of adverse outcomes. Data on patients were collected from January 1, 2011, to December 31, 2020. Blood samples were taken for Th1/Th2 cytokine, CRP, and PCT measurements at the initial onset of infection. Severe infection (SI) was defined as severe sepsis or septic shock. Th1/Th2 cytokine levels were determined by using flow cytometric bead array technology. In total, 7,735 febrile episodes were included in this study. For SI prediction, the AUCs of IL-6, IL-10 and TNF-α were 0.814, 0.805 and 0.624, respectively, while IL-6 and IL-10 had high sensitivity and specificity. IL-6 > 220.85 pg/ml and IL-10 > 29.95 pg/ml had high odds ratio (OR) values of approximately 3.5 in the logistic regression. Within the subgroup analysis, for bloodstream infection (BSI) prediction, the AUCs of IL-10 and TNF-α were 0.757 and 0.694, respectively. For multiorgan dysfunction syndrome (MODS) prediction, the AUC of CRP was 0.606. The AUC of PCT for mortality prediction was 0.620. In conclusion, IL-6 and IL-10 provide good predictive value for the diagnosis of SI. For children with SI, IL-10 and TNF-α are associated with BSI, while CRP and PCT are associated with MODS and death, respectively.


Subject(s)
Hematology , Neoplasms , Sepsis , Shock, Septic , Child , Humans , Procalcitonin , Cytokines , C-Reactive Protein , Interleukin-10 , Interleukin-6 , Tumor Necrosis Factor-alpha , Biomarkers
3.
Int J Cancer ; 154(6): 1111-1123, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-37842828

ABSTRACT

Effective screening and early detection are critical to improve the prognosis of gastric cancer (GC). Our study aims to explore noninvasive multianalytical biomarkers and construct integrative models for preliminary risk assessment and GC detection. Whole genomewide methylation marker discovery was conducted with CpG tandems target amplification (CTTA) in cfDNA from large asymptomatic screening participants in a high-risk area of GC. The methylation and mutation candidates were validated simultaneously using one plasma from patients at various gastric lesion stages by multiplex profiling with Mutation Capsule Plus (MCP). Helicobacter pylori specific antibodies were detected with a recomLine assay. Integrated models were constructed and validated by the combination of multianalytical biomarkers. A total of 146 and 120 novel methylation markers were found in CpG islands and promoter regions across the genome with CTTA. The methylation markers together with the candidate mutations were validated with MCP and used to establish a 133-methylation-marker panel for risk assessment of suspicious precancerous lesions and GC cases and a 49-methylation-marker panel as well as a 144-amplicon-mutation panel for GC detection. An integrated model comprising both methylation and specific antibody panels performed better for risk assessment than a traditional model (AUC, 0.83 and 0.63, P < .001). A second model for GC detection integrating methylation and mutation panels also outperformed the traditional model (AUC, 0.82 and 0.68, P = .005). Our study established methylation, mutation and H. pylori-specific antibody panels and constructed two integrated models for risk assessment and GC screening. Our findings provide new insights for a more precise GC screening strategy in the future.


Subject(s)
Helicobacter Infections , Helicobacter pylori , Stomach Neoplasms , Humans , Stomach Neoplasms/diagnosis , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , DNA Methylation , Early Detection of Cancer , Biomarkers , Risk Assessment , Helicobacter pylori/genetics , Biomarkers, Tumor/genetics , CpG Islands , Helicobacter Infections/diagnosis , Helicobacter Infections/genetics , Helicobacter Infections/pathology
4.
Leuk Lymphoma ; 65(1): 91-99, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37820046

ABSTRACT

Two hundred and thirty-one acute lymphoblastic leukemia (ALL) children with 1376 high-dose methotrexate (HD-MTX) courses (3-5 g/m2) were enrolled to analyze the influence of the plasma MTX concentration (CMTX) in ALL. The 24-h target peak CMTX (C24h) was set at 33 µmol/l for low-risk (LR) and 65 µmol/l for intermediate/high-risk (IR/HR) groups. The median C24h was 42.0 µmol/l and 69.7 µmol/l for LR and IR/HR groups, respectively. MTX excretion delay was observed in 14.6% of courses, which was more frequent in IR/HR groups (56.9% vs. LR group 40.2%, p = .014) and T-ALL patients (82.6% vs. B-ALL 47.1%, p = .001). MTX-related toxicities were more common in courses with MTX excretion delay. However, survival between the patients who failed to reach the target C24h or not, with or without MTX excretion delay, was comparable. These findings suggest that, owing to the effectiveness of risk stratification chemotherapy, CMTX does not exert an independent influence on the prognosis of childhood ALL.


Subject(s)
Methotrexate , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Child , Humans , Methotrexate/adverse effects , Antimetabolites, Antineoplastic/adverse effects , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Prognosis
6.
Front Cardiovasc Med ; 10: 1082019, 2023.
Article in English | MEDLINE | ID: mdl-37034341

ABSTRACT

Background: Major adverse cardiac events (MACE) are more likely to occur when abnormal heart rate recovery (HRR). This study aimed to assess the incremental predictive significance of HRR over exercise stress myocardial perfusion single-photon emission computed tomography (MPS) results for MACE in individuals with suspected coronary artery disease (CAD). Methods: Between January 2014 and December 2017, we continually gathered data on 595 patients with suspected CAD who received cycling exercise stress MPS. HRR at 1, 2, 3, and 4 min were used as study variables to obtain the optimal cut-off values of HRR for MACE. The difference between the peak heart rate achieved during exercise and the heart rate at 1, 2, 3, and 4 min was used to calculate the HRR, as shown in HRR3. Heart rate variations between two locations in time, such as HRR2 min-1 min, were used to establish the slope of HRR. All patients were followed for a minimum of 4 years, with MACE as the follow-up goal. The associations between HRR and MACE were assessed using Cox proportional hazards analyses. Results: Patients with MACE were older (P = 0.001), and they also had higher rates of hypertension, dyslipidemia, diabetes, abnormal MPS findings (SSS ≥ 5%), medication history (all P < 0.001), and lower HRR values (all P < 0.01). Patients with and without MACE did not significantly vary in their HRR4 min-3 min. The optimal cut-off of HRR1, 2, and 3 combined with SSS can stratify the risk of MACE in people with suspected CAD (all P < 0.001). HRR 1, 2, and 3 and its slope were linked to MACE in multivariate analysis, where HRR3 was the most significant risk predictor. With a global X2 increase from 101 to 126 (P < 0.0001), HRR3 demonstrated the greatest improvement in the model's predictive capacity, incorporating clinical data and MPS outcomes. Conclusions: HRR at 3 min has a more excellent incremental prognostic value for predicting MACE in patients with suspected CAD following cycling exercise stress MPS. Therefore, incorporating HRR at 3 min into known predictive models may further improve the risk stratification of the patients.

7.
Blood Adv ; 7(13): 2972-2982, 2023 07 11.
Article in English | MEDLINE | ID: mdl-36799929

ABSTRACT

Acute myeloid leukemia (AML) with retinoic acid receptor γ (RARG) rearrangement has clinical, morphologic, and immunophenotypic features similar to classic acute promyelocytic leukemia. However, AML with RARG rearrangement is insensitive to alltrans retinoic acid (ATRA) and arsenic trioxide (ATO) and carries a poor prognosis. We initiated a global cooperative study to define the clinicopathological features, genomic and transcriptomic landscape, and outcomes of AML with RARG rearrangements collected from 29 study groups/institutions worldwide. Thirty-four patients with AML with RARG rearrangements were identified. Bleeding or ecchymosis was present in 18 (54.5%) patients. Morphology diagnosed as M3 and M3v accounted for 73.5% and 26.5% of the cases, respectively. Immunophenotyping showed the following characteristics: positive for CD33, CD13, and MPO but negative for CD38, CD11b, CD34, and HLA-DR. Cytogenetics showed normal karyotype in 38% and t(11;12) in 26% of patients. The partner genes of RARG were diverse and included CPSF6, NUP98, HNRNPc, HNRNPm, PML, and NPM1. WT1- and NRAS/KRAS-mutations were common comutations. None of the 34 patients responded to ATRA and/or ATO. Death within 45 days from diagnosis occurred in 10 patients (∼29%). At the last follow-up, 23 patients had died, and the estimated 2-year cumulative incidence of relapse, event-free survival, and overall survival were 68.7%, 26.7%, and 33.5%, respectively. Unsupervised hierarchical clustering using RNA sequencing data from 201 patients with AML showed that 81.8% of the RARG fusion samples clustered together, suggesting a new molecular subtype. RARG rearrangement is a novel entity of AML that confers a poor prognosis. This study is registered with the Chinese Clinical Trial Registry (ChiCTR2200055810).


Subject(s)
Leukemia, Myeloid, Acute , Leukemia, Promyelocytic, Acute , Humans , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/genetics , Leukemia, Promyelocytic, Acute/genetics , Tretinoin , HLA-DR Antigens , Arsenic Trioxide
8.
Pediatr Hematol Oncol ; 40(4): 371-381, 2023 May.
Article in English | MEDLINE | ID: mdl-36111831

ABSTRACT

In contrast to the extensive knowledge on EVI1 in myeloid malignancies, few data are available on the EVI1 transcript in pediatric ALL. The purpose of this study was to examine the clinical and biological significance of EVI1 and validate its prognostic significance in pediatric patients with ALL. Here, we examined the clinical and biological significance of EVI1 expression, as measured by real-time polymerase chain reaction (PCR) in 837 children with newly diagnosed ALL treated on the National Protocol of Childhood Leukemia in China (NPCLC)-ALL-2008 protocol, and aimed to explore their prognostic significance in pediatric ALL patients. The EVI1 expression was detected in 27 of 837 (3.2%) patients. No statistically significant differences in prednisone response, complete remission (CR) rates and relapse rates were found between EVI1 overexpression (EVI1+) group and EVI1- group. Moreover, we found no significant difference in event-free survival (EFS) and overall survival (OS) between these two groups, also multivariate analysis did not identify EVI1+ as an independent prognostic factor. In the subgroup analysis, there was no difference in clinical outcome between EVI1+ and EVI1- patients in standard­risk (SR), intermediate-risk (IR) and high-risk (HR) groups. In the minimal residual disease (MRD)<10-4 group, EVI1+ patients have significantly lower EFS and OS rates compared to EVI1- patients. Further large­scale and well­designed prospective studies are required to confirm the results in the future.


Subject(s)
Leukemia, Myeloid, Acute , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Humans , Child , Prognosis , MDS1 and EVI1 Complex Locus Protein/genetics , MDS1 and EVI1 Complex Locus Protein/therapeutic use , Leukemia, Myeloid, Acute/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Virus Integration , Disease-Free Survival , Neoplasm, Residual
9.
Clin Chim Acta ; 537: 133-139, 2022 Dec 01.
Article in English | MEDLINE | ID: mdl-36283493

ABSTRACT

BACKGROUND AND AIMS: The aim of this study was to evaluate the performance of metagenomic next-generation sequencing (mNGS) in identifying microbiological etiologies in pediatric patients with hematological malignancies undergoing fever of unknown origin (FUO). METHODS: A total of 147 children with hematological malignancy suffering febrile diseases without definite microbiological etiologies under conventional tests were enrolled. The clinical record, serum inflammatory biomarkers and mNGS results were analyzed. RESULTS: At least one microorganism was identified by mNGS in 112 of 147 patients (76.2 %). Two or more types of organisms were detected simultaneously in 35.7 % (40/112) of samples. Of the 112 cases with positive mNGS results, the reported microorganisms were considered as etiologies of fever in 50 (44.6 %) cases. The initial antimicrobial regimens were adjusted according to the mNGS results in 48 cases, with 41 patients' febrile diseases resolved. Totally, 27.9 % (41/147) of patients benefit from mNGS. High IL-6 (>390 pg/mL) level was associated with bacterial infection and could help to interpret the results of mNGS. CONCLUSION: mNGS is a novel approach to determine the microbiological etiology of FUO in hematological malignancy patients, which benefits about a quarter of all patients tested. Integration of IL-6 can improve the diagnostic precision of bacterial infection.


Subject(s)
Bacterial Infections , Fever of Unknown Origin , Hematologic Neoplasms , Humans , Child , Fever of Unknown Origin/diagnosis , Fever of Unknown Origin/genetics , Interleukin-6 , Sensitivity and Specificity , High-Throughput Nucleotide Sequencing/methods , Hematologic Neoplasms/complications , Hematologic Neoplasms/genetics
10.
J Biophotonics ; 15(10): e202200075, 2022 10.
Article in English | MEDLINE | ID: mdl-35588374

ABSTRACT

This proposed optical imaging method is a nondestructive, real-time and high-resolution approach to distinguish healthy and injured temporomandibular joint (TMJ) tissues. And the TMJ health index was invented. TMJ pathologies are commonly and reported frequently. It could be associated with the damage of collagen, cartilage and bone tissue. The second harmonic generation images could be obtained by a femtosecond laser pulses, so the aligned information of the collagen fibers in all directions for the TMJ disorders was collected. The disorder degree of collagen fibers was quantified and ranked using a fast Fourier transform (FFT) method. The TMJ health index can effectively present the TMJ healthy condition and the disorder degree of collagen fibers, a valuable objective tool for tissue characterization for TMJ healthy condition. Integrated with the staining methods, we can provide the scaling information at different injury degree.


Subject(s)
Second Harmonic Generation Microscopy , Temporomandibular Joint Disorders , Collagen , Fourier Analysis , Humans , Temporomandibular Joint/diagnostic imaging , Temporomandibular Joint/pathology , Temporomandibular Joint Disorders/diagnostic imaging , Temporomandibular Joint Disorders/pathology
11.
Front Microbiol ; 13: 819467, 2022.
Article in English | MEDLINE | ID: mdl-35391735

ABSTRACT

The performance of metagenomic next-generation sequencing (mNGS) in identifying pathogens in immunocompromised children was not very clear. The purpose of this study is to assess the performance of mNGS in this population and to investigate whether the integration of serum cytokines and mNGS assay could improve diagnostic accuracy. We retrospectively collected the clinical data of pediatric patients who suffered febrile diseases and underwent mNGS determination simultaneously in the department of hematology/oncology between January 2019 and March 2021. Specimens were sent for conventional microbiological test (CMT), mNGS, and serum cytokine measurement in parallel. A total of 258 episodes of febrile diseases were enrolled, mNGS was positive in 224 cases, while CMT was positive in 78 cases. mNGS and CMT were both positive in 70 (27.1%) cases and were both negative in 26 (10.1%) cases. There were 154 (59.7%) cases positive by mNGS only while 8 (3.1%) were positive by CMT only. It was common that two or more pathogens were simultaneously detected by mNGS in a single specimen, with only 61 tests identified a single organism. Whether the organisms reported by mNGS were the microbiological etiology of infection was evaluated. Of the 224 cases with positive mNGS results, 135 (58.4%), 30 (13.0%), and 59 (28.6%) were considered as "probable," "possible," and "unlikely," respectively. Patients with high IL-6 (≥ 390 pg/ml) were likely to be bacterial infection. Although mNGS reported mixed pathogens, 84.6% (33/39) and 83.3% (10/12) of patients presenting high IL-6 were confirmed as bacterial infection in the training and validation cohort, respectively. In conclusion, mNGS analysis demonstrates promising diagnostic potential in rapidly identifying clinically relevant pathogens. Given the detection of many clinically irrelevant organisms, the integration of IL-6 improves the precision of mNGS results interpretation.

12.
Endoscopy ; 54(9): 848-858, 2022 09.
Article in English | MEDLINE | ID: mdl-34963146

ABSTRACT

BACKGROUND : The effectiveness of endoscopic screening on gastric cancer has not been widely investigated in China and the screening interval of repeated screening has not been determined. METHODS : In a population-based prospective study, we included 375,800 individuals, 14,670 of whom underwent endoscopic screening (2012-2018). We assessed the associations between endoscopic screening and risk of incident gastric cancer and gastric cancer-specific mortality, and examined changes in overall survival and disease-specific survival following screening. The optimal screening interval for repeated endoscopy for early detection of gastric cancer was explored. RESULTS : Ever receiving endoscopic screening significantly decreased the risk of invasive gastric cancer (age- and sex-adjusted relative risk [RR] 0.69, 95 % confidence interval [CI] 0.52-0.92) and gastric cancer-specific mortality (RR 0.33, 95 %CI 0.20-0.56), particularly for noncardia gastric cancer. Repeated screening strengthened the beneficial effect on invasive gastric cancer-specific mortality of one-time screening. Among invasive gastric cancers, screening-detected individuals had significantly better overall survival (RR 0.18, 95 %CI 0.13-0.25) and disease-specific survival (RR 0.18, 95 %CI 0.13-0.25) than unscreened individuals, particularly for those receiving repeated endoscopy. For individuals with intestinal metaplasia or low grade intraepithelial neoplasia, repeated endoscopy at an interval of < 2 years, particularly within 1 year, significantly enhanced the detection of early gastric cancer, compared with repeated screening after 2 years (P-trend = 0.02). CONCLUSION : Endoscopic screening prevented gastric cancer occurrence and death, and improved its prognosis in a population-based study. Repeated endoscopy enhanced the effectiveness. Screening interval should be based on gastric lesion severity.


Subject(s)
Stomach Neoplasms , Early Detection of Cancer/methods , Endoscopy, Gastrointestinal , Humans , Mass Screening/methods , Prospective Studies , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/prevention & control
13.
EBioMedicine ; 74: 103714, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34818622

ABSTRACT

BACKGROUND: Molecular features underlining the multistage progression of gastric lesions and development of early gastric cancer (GC) are poorly understood, restricting the ability to GC prevention and management. METHODS: We portrayed proteomic landscape and explored proteomic signatures associated with progression of gastric lesions and risk of early GC. Tissue proteomic profiling was conducted for a total of 324 subjects. A case-control study was performed in the discovery stage (n=169) based on populations from Linqu, a known high-risk area for GC in China. We then conducted two-stage validation, including a cohort study from Linqu (n = 56), with prospective follow-up for progression of gastric lesions (280-473 days), and an independent case-control study from Beijing (n = 99). FINDINGS: There was a clear distinction in proteomic features for precancerous gastric lesions and GC. We derived four molecular subtypes of gastric lesions and identified subtype-S4 with the highest progression risk. We found 104 positively-associated and 113 inversely-associated proteins for early GC, with APOA1BP, PGC, HPX and DDT associated with the risk of gastric lesion progression. Integrating these proteomic signatures, the ability to predict progression of gastric lesions was significantly strengthened (areas-under-the-curve=0.88 (95%CI: 0.78-0.99) vs. 0.56 (0.36-0.76), Delong's P = 0.002). Immunohistochemistry assays and examination at mRNA level validated the findings for four proteins. INTERPRETATION: We defined proteomic signatures for progression of gastric lesions and risk of early GC, which may have translational significance for identifying particularly high-risk population and detecting GC at an early stage, improving potential for targeted GC prevention. FUNDING: The funders are listed in the Acknowledgement.


Subject(s)
Precancerous Conditions/metabolism , Proteomics/methods , Stomach Neoplasms/metabolism , Case-Control Studies , China , Chromatography, Liquid , Disease Progression , Humans , Precancerous Conditions/genetics , Prospective Studies , Stomach Neoplasms/genetics , Tandem Mass Spectrometry
14.
Mitochondrial DNA B Resour ; 6(8): 2342-2344, 2021.
Article in English | MEDLINE | ID: mdl-34345691

ABSTRACT

Potato (Solanum tuberosum L.), a species of the family Solanaceae, is the fourth most important food crop worldwide. Solanum tuberosum L. cv. Shepody is a long, smooth, white-skinned potato cultivar with medium green leaves. It has good specific gravity and boils and bakes well. To support more molecular data for breeding of S. tuberosum, the complete chloroplast (cp) genome sequence of S. tuberosum L. cv. Shepody was determined using the next-generation sequencing. In leaves, the chloroplast genome accounts for 3.88% of the total genome. The entire cp genome was determined to be 155,296 bp in length. It contained large single-copy (LSC) and small single-copy (SSC) regions of 85,737 and 18,373 bp, respectively, which were separated by a pair of 25,593 bp inverted repeat (IR) regions. The genome contained 132 total genes, including 87 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The overall GC content of the genome is 37.9%. A phylogenetic tree reconstructed by 60 chloroplast genomes reveals that S. tuberosum L. cv. Shepody was closely related to S. tuberosum L. cv. Desiree with bootstrap support values of 100%.

15.
Eur J Pharmacol ; 908: 174346, 2021 Oct 05.
Article in English | MEDLINE | ID: mdl-34270985

ABSTRACT

Non-small cell lung cancer (NSCLC) is the most common cancer in the world. Gefitinib, an inhibitor of EGFR tyrosine kinase, is highly effective in treating NSCLC patients with activating EGFR mutations (L858R or Ex19del). However, despite excellent disease control with gefitinib therapy, innate resistance and inevitable acquired resistance represent immense challenges in NSCLC therapy. Gefitinib potently induces cytoprotective autophagy, which has been implied to contribute to both innate and acquired resistance to gefitinib in NSCLC cells. Currently, abrogation of autophagy is considered a promising strategy for NSCLC therapy. In the present study, YC-1, an inhibitor of HIF-1α, was first found to significantly inhibit the autophagy induced by gefitinib by disrupting the fusion of autophagosomes and lysosomes and thereby enhancing the proapoptotic effect of gefitinib in gefitinib-resistant NSCLC cells. Furthermore, the combinational anti-autophagic and pro-apoptotic effect of gefitinib and YC-1 was demonstrated to be associated with an enhanced of forkhead box protein O1 (FOXO1) transcriptional activity which resulted from an increase in the p-FOXO1 protein level in gefitinib-resistant NSCLC cells. Our data suggest that inhibition of autophagy by targeting FOXO1 may be a feasible therapeutic strategy to overcome both innate and acquired resistance to EGFR-TKIs.


Subject(s)
Gefitinib , Carcinoma, Non-Small-Cell Lung , ErbB Receptors , Humans , Lung Neoplasms
16.
Clin Orthop Surg ; 13(2): 261-265, 2021 Jun.
Article in English | MEDLINE | ID: mdl-34094018

ABSTRACT

BACKGROUD: The accessory tendon of the extensor hallucis longus (ATEHL) muscle is a common abnormal structure, and its clinical significance remains debatable. In this study, we provide the incidence of the ATEHL and characterize its morphological types in Asian cadavers and investigate its clinical applications. METHODS: The tendons from 50 adult cadaveric feet, fixed in 10% formalin, were analyzed. We measured the length and width of both the ATEHL and the extensor hallucis brevis (EHB). RESULTS: All dissected specimens had an ATEHL. The first metatarsophalangeal joint was surrounded by an accessory tendon that inserted onto the joint capsule and the dorsal base of the proximal phalanx. We classified the ATEHL into 3 types based on their directions. Differences in ATEHL type based on sex were not statistically significant. CONCLUSIONS: We found an ATEHL in all cadaveric specimens in this study. We surmise that the ATEHL acts as an antagonist with the EHB when the toe is extending, which might help prevent the occurrence of hallux valgus deformity.


Subject(s)
Anatomic Variation , Hallux/anatomy & histology , Metatarsophalangeal Joint/anatomy & histology , Tendons/anatomy & histology , Aged , Aged, 80 and over , Cadaver , Female , Humans , Incidence , Male
17.
Curr Probl Cancer ; 45(6): 100758, 2021 12.
Article in English | MEDLINE | ID: mdl-34034913

ABSTRACT

OBJECTIVES: Conflicting data have been published regarding the prognostic impact of the t(1;19)/TCF3-PBX1 translocation in childhood ALL. The objective of this study was to explore the correlation between the TCF3-PBX1 fusion gene and clinical outcome in Chinese children with newly diagnosed ALL. METHODS: In order to address this issue in our setting, we summarized and analyzed the data of 837 Chinese children with ALL diagnosed between 2010 and 2017. All the patients were treated with the National Protocol of Childhood Leukemia in China (NPCLC)-ALL-2008 protocol. Clinical characteristics and prognosis of pediatric ALL patients with or without TCF3-PBX1 rearrangement were analyzed and compared retrospectively. RESULTS: The TCF3-PBX1 fusion gene was identified in 48 (5.7%) of 837 children with ALL. Our results showed that TCF3-PBX1 positive patients had higher pretreatment white blood cell counts, higher PB blasts percentages and worse risk classification at diagnosis. No statistically significant differences in CR rates, response to prednisone and relapse rates were found between TCF3-PBX1-positive and -negative patients. The 5-year predicted EFS, RFS, and OS of the TCF3-PBX1 positive group compared with the control group were 86.2%±5.3% vs 85.4%±1.3% (P=0.657), 88.2%±5.1% vs 92.2%±1.0% (P=0.458) and 90.4%±4.6% vs 89.0%±1.1% (P=0.561), respectively. No differences were observed regarding clinical outcome between these two groups. When compared with standard risk, intermediate risk and high risk group patients, the long-term survival of TCF3/PBX1 positive group was approximately similar to that of the intermediate risk group under the same protocol in our single center. CONCLUSION: In contrast to previous studies, childhood ALL patients with TCF3-PBX1 transcripts do not appear to show a better outcome than their negative counterparts. TCF3/PBX1 positive was a definitive intermediate risk factor with our NPCLC-ALL-2008 protocol.


Subject(s)
Oncogene Proteins, Fusion/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Adolescent , Antineoplastic Agents, Hormonal/therapeutic use , Child , Child, Preschool , China/epidemiology , Female , Humans , Infant , Male , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Prednisone/therapeutic use , Prognosis , Retrospective Studies , Risk Factors , Survival Rate , Translocation, Genetic
18.
Mitochondrial DNA B Resour ; 6(3): 909-911, 2021 Mar 16.
Article in English | MEDLINE | ID: mdl-33796677

ABSTRACT

Potato (Solanum tuberosum L.), a species of the family Solanaceae, is the fourth most important food crop worldwide. Solanum tuberosum L. cv. Favorita is a long oval, smooth, yellowish-skinned potato variety with green and plump leaves. It has a dry matter content of 17.7% and starch content of 12.4-14.01% in the tuber. In order to support more genetic data for the taxonomy of S. tuberosum, the complete chloroplast (cp) genome sequence of S. tuberosum L. cv. Favorita was determined using next-generation sequencing. In leaves, the chloroplast genome accounts for 5.17% of the total genome. The entire cp genome was determined to be 155,296 bp in length. It contained large single-copy (LSC) and small single-copy (SSC) regions of 85,737 and 18,373 bp, respectively, which were separated by a pair of 25,593 bp inverted repeat (IR) regions. The genome contained 132 total genes, including 87 protein-coding genes, 37 tRNA genes, and eight rRNA genes. The overall GC content of the genome is 37.9%. A phylogenetic tree reconstructed by 60 chloroplast genomes reveals that S. tuberosum L. cv. Favorita is most closely related to S. tuberosum L. cv. Desiree and S. tuberosum L. cv. Atlantic.

19.
Mitochondrial DNA B Resour ; 6(1): 73-75, 2021 Jan 08.
Article in English | MEDLINE | ID: mdl-33521272

ABSTRACT

Potato (Solanum tuberosum L.), a species of the family Solanaceae, is the fourth most important food crop worldwide. Solanum tuberosum L. cv. Atlantic, a main fried special potato, has a dry matter content of 19%-23% and a starch content of 16.26% in the tuber. In order to support more molecular data for the taxony of S. tuberosum, the complete chloroplast (cp) genome sequence of S. tuberosum L. cv. Atlantic was determined using next-generation sequencing. In leaves, the chloroplast genome accounts for 5.49% of the total genome. The entire cp genome was determined to be 155,296 bp in length. It contained large single-copy (LSC) and small single-copy (SSC) regions of 85,737 and 18,373 bp, respectively, which were separated by a pair of 25,593 bp inverted repeat (IR) regions. The genome contained 132 genes, including 87 protein-coding genes, 37 tRNA genes, and eight rRNA genes. The overall GC content of the genome is 37.9%. A phylogenetic tree reconstructed by 64 chloroplast genomes reveals that S. tuberosum L. cv. Atlantic is most closely related to Solanum tuberosum L. cv. Desiree.

20.
Int J Hematol ; 113(5): 751-759, 2021 May.
Article in English | MEDLINE | ID: mdl-33392975

ABSTRACT

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematological malignancy with poor outcome. Four children with BPDCN treated at our hospital were enrolled. All the four cases presented with cutaneous lesions. Bone marrow and central nervous system was involved in 50% and 25% of patients, respectively. The whole exome sequencing analysis revealed that KMT2 family genes were the most frequently mutated (4/4, 100%), followed by IKZF2 (2/4, 50%). The point mutation p.D348N was found in three patients and one patient had p.C394Y mutation in the KMT2C gene. Translocation of KMT2A-MLLT3 was found in Case 2. Case 1 had complex karyotype, who was induced by acute myeloid leukemia-like regimens. Although he received allogeneic hematopoietic stem cell transplantation twice as well as CD123 chimeric antigen receptor T cell therapy, the disease still progressed and he died 37 months after diagnosis. The other three patients were treated with Interfant-99 protocol. They tolerated the therapy well without significant toxicities and now in complete remission so far with a median follow up time of 9 months. More studies are needed to address the question whether the complex karyotype and KMT2 family genes are the causes of the relapse and refractory in BPDCN.


Subject(s)
Dendritic Cells/pathology , Hematologic Neoplasms/pathology , Skin Neoplasms/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Child , Female , Hematologic Neoplasms/diagnosis , Hematologic Neoplasms/genetics , Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation , Histone-Lysine N-Methyltransferase/genetics , Humans , Ikaros Transcription Factor/genetics , Male , Myeloid-Lymphoid Leukemia Protein/genetics , Point Mutation , Skin Neoplasms/diagnosis , Skin Neoplasms/genetics , Skin Neoplasms/therapy , Translocation, Genetic , Exome Sequencing
SELECTION OF CITATIONS
SEARCH DETAIL
...