查看更多>>摘要：Background: Extranodal involvement is recognized as a poor prognostic factor for diffuse large B-cell lymphoma (DLBCL). However, the prognostic differences of patients with refractory/relapsed (R/R) nodal and extranodal DLBCL in the chimeric antigen receptor T cell (CART) therapy era are still unclear. Materials and methods: In this study, 18 R/R nodal DLBCL (R/R N-DLBCL) and 19 R/R extranodal DLBCL (R/R EN-DLBCL) were enrolled to compare clinical outcomes. Results: The median follow-up time was 13 (range, 1-47) months and one-year progression-free survival (PFS; 83.3% vs. 42.1%, P = 0.008) and one-year overall survival (OS; 94.4% vs. 63.2%, P = 0.020) were significantly different between nodal and extranodal patients. In the multivariable Cox regression analysis, R/R EN-DLBCL was associated with worse PFS (hazard ratio [HR] = 4.263, P = 0.018) and OS (HR = 9.589, P = 0.034) compared to R/R N-DLBCL. Additionally, autologous hematopoietic stem cell transplantation (ASCT) combined with CART therapy (ASCT + CART) was correlated with better PFS (HR = 0.164, P = 0.003) compared to CART treatment alone. Conclusions: The clinical outcomes of R/R EN-DLBCL were worse than R/R N-DLBCL in patients receiving CART therapy and ASCT + CART therapy is a promising alternative treatment for patients with R/R EN-DLBCL.
Steyaert, WouterVarney, Matthew J.Benovic, Jeffrey L.Creemers, John...
5页
查看更多>>摘要：Background: A hitherto undescribed form of diabetes mellitus type 2 is reported in a Flemish family. In these patients, markedly elevated gastrin levels were observed, which could not be linked to gastrointestinal symptoms. Materials and methods: Gel permeation chromatography was performed for gastrin, insulin, and proinsulin. Proprotein convertase subtilisin/kexin type (PCSK1 and PCSK2)] were sequenced. Whole-exome sequencing was performed on the genomic DNA extracted from leukocytes of the proband of the family. Results: Gel permeation chromatography revealed that the apparent hypergastrinemia was caused by the accumulation of biologically inactive progastrin. Besides, high serum concentrations of proinsulin and intact fibroblast growth factor 23 (FGF23) were also detected. Sequencing of PCSK1 and PCSK2 genes did not reveal any mutations in these genes. Whole exome sequencing revealed a c.1150C > T (p.Pro384Ser) mutation in G proteincoupled receptor kinase 6 (GRK6), which cosegregated with the disease. Expression of the mutant enzyme in mammalian cells revealed that it was mislocalized compared to the wild-type GRK6. Conclusions: In the affected patients, prohormone processing is impaired likely due to the altered function of mutant GRK6. Delayed pro-insulin processing causes hypoglycaemia episodes a couple of hours following meals. In addition, increased plasma concentrations of progastrin and intact FGF23 in the affected individuals can be explained by incomplete processing of the precursor hormones.
查看更多>>摘要：Background: Immune checkpoint inhibitors (ICIs) have achieved important outcomes in cancer treatment. However, current clinical biomarker tests are not suitable for some patients because they require tumor tissues and have poor predictive value for treatment responses. Therefore, the identification of biomarkers that enable screening tests in all patients is necessary. Methods: We performed an immune complexome analysis of non-small cell lung cancer patients treated with nivolumab to comprehensively identify and compare antigens incorporated into immune complexes (IC -antigens) in serum samples from the responders (n = 15) and non-responders (n = 20). Additionally, combinations of IC-antigens characteristic to the responder group were evaluated by logistic regression analysis and receiver operating characteristics curves to examine their predictiveness for ICI treatment responses. Results: The combination of predictive biomarkers detected before treatment was profilin-1, purine nucleoside phosphorylase, alpha-enolase, and nucleoside diphosphate kinase A [p = 0.0043, odds ratio = 2.26, 95% confidence interval (CI) = 1.19-4.28, area under the curve = 0.76]. The combination of predictive biomarkers detected after treatment was peptidyl-prolyl cis-trans isomerase A, ubiquitin-like modifier-activating enzyme 1, complement component C8 beta chain, and apolipoprotein L1 (p = 0.0039, odds ratio = 2.56, 95% CI = 1.25-5.23, area under the curve = 0.77). Conclusion: Combinations of serum IC-antigens may predict the therapeutic effect of nivolumab in non-small cell lung cancer patients.
查看更多>>摘要：Background: Determining what quarantine period and detection strategy are more effective and sustainable remains a challenge for further prevention and social stability. Methods: From October 2020 to December 2021, 290,547 inbound overseas travelers were subject to government quarantine in Xiamen, China. The detection rate of COVID-19 during different quarantine periods using dual or single nucleic acid testing reagents. Results: The COVID-19 positive rate was 1.79% (519/290,547). The detection rates during the 7-day, 14-day and 14+7-day quarantine periods using the dual reagents were 78.4%, 91.7%, and 100%, respectively. The detection rate of the 7-day, 14-day and 14+7-day quarantine periods were 73.99%, 86.51%, and 94.22%, respectively, using the Liferiver reagent and 72.25%, 84.59%, and 91.91%, respectively, using the Daan reagent. Based on the 14+7 day strategy, dual nucleic acid testing reagent strategy detected all imported cases, but 30 cases (5.78%) were not detected via Liferiver reagent and 42 (8.09%) cases not detected via Daan reagent. Conclusion: A 14+7-day quarantine period and dual nucleic acid testing reagent strategy are effective screening methods for COVID-19 among inbound overseas travelers. The superior detection rate of these strategies reduce the risk of secondary transmission of the SARS-CoV-2 virus.
查看更多>>摘要：Cancer remains a common health issue having significant socioeconomic burden worldwide. Despite the awareness campaigns, cancer cases continue to increase due to an aging population and lack of early detection biomarkers. Accordingly, much research has focused on non-traditional approaches which include novel imaging modalities and liquid biopsy. In addition, a considerable number of biomacromolecules as well as other biomarkers have been identified to further explore their potential use as diagnostic, prognostic and therapeutic tools. In this review, we provide an update on these new findings and explore their clinical application in cancer.
查看更多>>摘要：Background: Isolated sulfite oxidase deficiency (ISOD) is a rare type of life-threatening neurometabolic disorders characterized by neonatal intractable seizures and severe developmental delay with an autosomal recessive mode of inheritance. Germline mutation in SUOX gene causes ISOD. Till date, only 32 mutations of SUOX gene have been identified and reported to be associated with ISOD. Methods: Here, we investigated a 5-days old Chinese female child, presented with intermittent tremor or seizures of limbs, neonatal encephalopathy, subarachnoid cyst and haemorrhage, dysplasia of corpus callosum, neonatal convulsion, hyperlactatemia, severe metabolic acidosis, hyperglycemia, and hyperkalemia. Results: Whole exome sequencing identified a novel homozygous transition (c.1227G > A) in exon 6 of the SUOX gene in the proband. This novel homozygous variant leads to the formation of a truncated sulfite oxidase (p. Trp409*) of 408 amino acids. This variant causes partial loss of the dimerization domain of sulfite oxidase. Hence, it is a loss-of-function variant. Proband's father and mother is carrying this novel variant in a heterozygous state. This variant was not found in 200 ethnically matched normal healthy control individuals. Conclusions: Our study not only expanded the mutational spectrum of SUOX gene associated with ISOD, but also strongly suggested the significance of whole exome sequencing for identifying candidate genes and novel diseasecausing variants.
查看更多>>摘要：Background/aims: Chimerism monitoring by means of high-throughput sequencing or quantitative PCR of biallelic single nucleotide and insertion/deletion polymorphisms has shown potential for improved patient care when compared to the gold standard capillary electrophoresis assays. When designing chimerism assays the number of markers to screen needs consideration: it determines the informativity rate and accuracy of the assay, but screening too many markers increases the assay's cost and complexity. The minimal number of biallelic markers to screen is currently unstudied.Materials/methods: A simulation framework accounting for marker minor allele frequencies, the number of markers screened, marker allelic constellations and donor-recipient relatedness was constructed. The framework was validated through analysis of 324 clinical samples.Results: Empirical clinical data confirm the validity of the simulation framework. With guidelines suggesting to monitor at least three informative markers, we demonstrate that, for optimized assays, at least 40 biallelic markers need to be screened to achieve enough informative markers in over 99% of cases. We propose and discuss several assay optimization strategies.Conclusion: Currently used chimerism assays often screen too little or too many markers, leaving room for optimization. Through support of the simulation framework here introduced and validated, more informative, cost-effective chimerism assays can be designed.
查看更多>>摘要：Both infection with and vaccination against SARS-CoV-2 trigger a complex B-cell and T-cell response. Methods for the analysis of the B-cell response are now well established. However, reliable methods for measuring the T cell response are less well established and their usefulness in clinical settings still needs to be proven. Here, we have developed and validated a T-cell proliferation assay based on 3H thymidine incorporation. The assay is using SARS-CoV-2 derived peptide pools that cover the spike (S), the nucleocapsid (N) and the membrane (M) protein for stimulation. We have compared this novel SARS-CoV-2 lymphocyte transformation test (SARS-CoV-2 LTT) to an established ELISA assay detecting Immunoglobulin G (IgG) antibodies to the S1 subunit of the SARSCoV-2 spike protein. The study was carried out using blood samples from both vaccinated and infected health care workers as well as from a non-infected control group. Our novel SARS-CoV-2 LTT shows excellent discrimination of infected and/or vaccinated individuals versus unexposed controls, with the ROC analysis showing an area under the curve (AUC) of > 0.95. No false positives were recorded as all unexposed controls had a negative LTT result. When using peptide pools not only representing the S protein (found in all currently approved vaccines) but also the N and M proteins (not contained in the vast majority of vaccines), the novel SARS-CoV-2 LTT can also discriminate T-cell responses resulting from vaccination against those induced by infection.
查看更多>>摘要：Background: Missense variants in MED12 are associated with MED12-related disorders. We aimed to clarify the molecular level changes and underlying pathogenic mechanism of a female patient in our study.Methods: We reported a Chinese girl with clinical characteristics similar to MED12-related disorders. Trio whole exome sequencing (WES) was performed to identify related pathogenic variant(s) and RNA sequencing (RNAseq) was subsequently applied to evaluate the effect of identified variant(s) on mRNA splicing. Moreover, Xchromosome inactivation (XCI) assay based on AR and RP2 was performed to reveal the XCI pattern of the female patient. Results: The proband manifested mainly as mental retardation and language impairment. Trio WES revealed a novel heterozygous variant c.3354 + 5 G > A in intron 23 of MED12. RNA-seq identified two aberrant transcripts. XCI assay on AR revealed a homozygous result, while XCI based on RP2 showed random pattern in peripheral blood. Conclusion: In conclusion, we identified a novel variant c.3354 + 5 G > A by WES combined with RNA-seq, which extends the spectrum of MED12 variants and provide a basis for further genetic counseling. According to the result of two aberrant transcripts by RNA-seq, we speculate that our patient's milder clinical feature may be the consequence of multiple different transcripts.
查看更多>>摘要：Osteoarthritis (OA) is a progressive joint disease that affects millions of older adults around the world. With increasing rates of incidence and prevalence worldwide, OA has become an enormous global socioeconomic burden on healthcare systems. Long non-coding ribonucleic acids (lncRNAs), essential functional molecules in many biological processes, are a group of non-coding RNAs that are greater than approximately 200 nucleotides in length. Fast-growing and recent developments in lncRNA research are captivating and represent a novel and promising field in understanding the complexity of OA pathogenesis. The involvement of lncRNAs in OA's pathological processes and their altered expressions in joint tissues, blood and synovial fluid make them attractive candidates for the diagnosis and treatment of OA. We focus on the recent advances in major regulator mechanisms of lncRNAs in the pathophysiology of OA and discuss potential diagnostic and therapeutic uses of lncRNAs for OA. We investigate how upregulation or downregulation of lncRNAs influences the pathogenesis of OA and how we can use lncRNAs to elucidate the molecular mechanism of OA. Furthermore, we evaluate how we can use lncRNAs as a diagnostic marker or therapeutic target for OA. Our study not only provides a comprehensive review of lncRNAs regarding OA's pathogenesis but also contributes to the elucidation of its molecular mechanisms and to the development of diagnostic and therapeutic approaches for OA.
NSTL
Elsevier