Exploring the efficacy and safety of anti-BCMA chimeric antigen receptor T-cell therapy for multiple myeloma: Systematic review and meta-analysis.

Objective: Multiple myeloma (MM) is a bone marrow cancer that profoundly affects plasma cells involved in the immune response. Myeloma cells alter the average production of cells in the bone marrow. Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy allows genetic modifications of an individual's T-cells to increase the expression of CARs used to identify and attach BCMA proteins to the malignant cells. Our main objective is to perform a systematic review and meta-analysis to explore the efficacy and safety of anti-BCMA CAR T-cell therapy for MM. Material and Methods: We searched five databases, PubMed, CNKI, EMBASE, Cochrane, Web of Science, and CNKI, for studies published on anti-BCMA,CAR-T-cell treatment for MM. Inclusion criteria involved prospective single-arm studies either single or multi-center, in various MM phases and studies that reported anti-BCMA,CAR-T-cell treatment for MM. We excluded non-English publications and conference papers. All statistical analyses were performed in R software and Review Manager 5.4.1. Results: Thirteen articles were included in the analysis. We found that the overall response survival complete response increase was statistically significant. Similarly, the reduction in cytokine release syndrome grades 3 and 4 and neurotoxicity after follow-up was statistically significant. However, the reduction in minimal residual disease negativity (MRDN) was not statistically significant. Conclusion: Using anti-BCMA CAR T-cell therapy in MM was highly efficacious and safe in lowering the adverse outcomes and improving the survival outcomes, complete response, and overall response.

Co-occurrence of Spondyloepiphyseal Dysplasia and X-Linked Hypophosphatemia in a Three-Generation Chinese Family.

Rare genetic skeletal disorders (GSDs) remain the major problem in orthopedics and result in significant morbidity in patients, but the causes are highly diverse. Precise molecular diagnosis will benefit management and genetic counseling. This study aims to share the diagnostic experience on a three-generation Chinese family with co-occurrence of spondyloepiphyseal dysplasia (SED) and X-linked hypophosphatemia (XLH), and evaluate the therapeutic effects of two third-generation siblings. The proband, his younger brother, and mother presented with short stature, skeletal problems, and hypophosphatemia. His father, paternal grandfather, and aunt also manifested short stature and skeletal deformities. Whole exome sequencing (WES) of proband-brother-parents initially only found the proband and his younger brother had a pathogenic c.2833G > A(p.G945S) variant in the COL2A1 gene inherited from their father. Re-analysis of WES uncovered the proband and his younger brother also harbored a pathogenic ex.12 del variant in the PHEX gene transmitted from their mother. Sanger sequencing, agarose gel electrophoresis, and quantitative polymerase chain reaction proved these results. The proband and his younger brother were confirmed to have a paternally inherited SED and a maternally inherited XLH. During a 2.8-year follow-up, these two siblings remained short stature and hypophosphatemia, but their radiographic signs and serum bone alkaline phosphatase levels were improved with treatment of oral phosphate and calcitriol. Our study presents the first report of co-occurrence of SED and XLH, shows the possibility that two different rare GSDs co-exist in a single patient, and alerts clinicians and geneticists to be cautious about this condition. Our study also suggests that next-generation sequencing has limit in detecting exon-level large deletions.

Comparability of JAK2 p.V617F allele burden in peripheral blood and that in bone marrow in patients with suspected myeloproliferative neoplasms: a single-center prospective study.

PURPOSE: To detect JAK2 p.V617F and measure allele burden in peripheral blood (PB) and bone marrow (BM) aspirates in patients with suspected myeloproliferative neoplasms (MPNs). METHODS: Patients with suspected MPNs were prospectively enrolled between August 2017 and May 2019, and their PB and BM were collected during the same period. Quantitative fluorescence polymerase chain reaction (PCR) was used to detect the copy number of JAK2 wild type and the V617F mutant; the JAK2 V617F proportion was also calculated. The JAK2 p.V617F proportion in PB was compared to that in BM by Chi-square test. RESULTS: Among 54 patients with suspected MPNs, 43 of them were eligible for analysis. The JAK2 p.V617F in PB had the same sensitivity and specificity as BM (all P>0.05). The Chi-square test suggested that the JAK2 p.V617F allele burden of PB was comparable to that of BM (Spearman Correlation =0.986; P=0.000). CONCLUSION: PB could be used as an alternative to BM for JAK2 p.V617F measurement in patients with suspected MPNs.

Insight into the Transformation Behaviors of Dioxins from Sintering Flue Gas in the Cyclic Thermal Regeneration by the V2O5/AC Catalyst-sorbent.

Dioxins in the sintering flue gas are usually removed through integrated elimination technologies by carbonaceous catalysts. However, the regeneration of the used catalyst is poorly investigated, leading to the risk of leakage of dioxins. Herein, the influences of cyclic regenerations on the dioxin removal performance of a catalyst (V2O5/AC) were investigated systematically with dibenzofuran (DBF) as a model pollutant. It was demonstrated that the adsorption capacity and oxidation activity of catalysts significantly declined after several regeneration cycles due to the decreasing external specific surface area and V5+, respectively. Compared with 79.12% DBF directly emitted from a regenerator during N2 regeneration, the emission of DBF was only 29.93% with the modification of the regeneration process through O2 addition and temperature adjustment. The possible regenerated products were also analyzed to disclose the transformation behaviors of DBF. The regeneration mechanisms of DBF followed the transformation pathway of dibenzofuranol, benzofuran, anhydride species, and ultimately to CO2 and H2O. Moreover, the accumulated heavy aromatics on the surface could be decomposed by introducing O2. This research provides a comprehensive understanding of dioxin transformation behavior and a theoretical basis for efficient control of dioxin removal in the whole integrated removal technologies.

Follicular Lymphoma Presenting With Monoclonal IgM And MYD88 Mutation: A Case Report And Review Of The Literature.

MYD88 mutation has been reported in various lymphomas, specifically in lymphoplasmacytic lymphoma. Yet, the mutation has not been reported in primary follicular lymphoma. Here, we present a 62-year-old male with follicular lymphoma who had an MYD88 L265P somatic mutation and monoclonal IgM gammopathy. He received four cycles of R-CHOP immunochemotherapy. Interim PET/CT evaluation indicated a state of stable disease (SD). Neither did serum IgM remarkably drop. He was then given a bortezomib-contained regimen which significantly reduced the level of serum IgM. To the best of our knowledge, this is the first report of follicular lymphoma with monoclonal IgM and MYD88 L265P mutation. The present case indicated bortezomib may benefit these patients.

Prognostic value of EGFR and KRAS in resected non-small cell lung cancer: a systematic review and meta-analysis.

BACKGROUND: The prognostic value of EGFR and KRAS mutations in resected non-small cell lung cancer (NSCLC) has been reported. However, conflicting results were reported in these studies. The effect of mutations in these two genes in resected NSCLC remains controversial. METHODS: We searched Internet databases for studies reporting disease-free survival (DFS) and overall survival (OS) in resected NSCLC patients with EGFR or KRAS mutations. A meta-analysis calculating the pooled hazard ratio (HR) for DFS and OS was used to measure the association of EGFR or KRAS mutations with the prognosis of patients after surgery. RESULTS: A total of 9,635 patients from 32 studies were included in this analysis. The combined HR for EGFR mutations on DFS was 0.77 (95% CI 0.66-0.90, p=0.001) and on OS was 0.72 (95% CI 0.66-0.80, p<0.00001). In addition, the combined HR for KRAS mutations on DFS was 1.5 (95% CI 1.15-1.96, p=0.002) and on OS was 1.49 (95% CI 1.28-1.73, p<0.00001). Sensitivity analysis, subgroup analysis, and bias analysis proved the stability of the results. CONCLUSION: The analysis showed that EGFR mutations were significantly associated with DFS and OS. These findings indicated that surgically treated NSCLC patients with EGFR mutations were inclined to exhibit a prolonged DFS and OS. In addition, the results indicated that KRAS mutations predicted worse DFS and OS in patients with resected NSCLC.

Identifying key regulating miRNAs in hepatocellular carcinomas by an omics' method.

The miRNAs play important regulating roles in the pathogenesis of hepatocellular carcinoma (HCC). To uncover key regulating miRNAs in HCC that were neglected by traditional analyzing methods of transcriptomics data, we proposed a novel molecular-network-based omics' (MNBO) method. With this method, we predicted HCC-regulating miRNAs, and confirmed the role of a novel miR-590-3P/EED axis by a clinical study and in vitro, in vivo wet-experiments. The miR-590-3P is significantly down-regulated in HCC patients. And low level of miR-590-3P in HCC is associated with poor prognosis of patients. In HCC cell lines, the miR-590-3P suppressed cell proliferation by inhibiting the transformation G1 phase to S phases of the cell cycle. Moreover, the miR-590-3P inhibited migration and invasion of HCC cells. Further investigations indicated that miR-590-3P play its roles by inhibiting polycomb protein EED. The experiments in animal model implied miR-590-3P could be a potential therapeutic agent for HCC in the future. In conclusion, the discovery of miR-590-3P revealed the MNBO would be a useful strategy to uncover key regulating miRNAs in HCC.

Driver genes in non-small cell lung cancer: Characteristics, detection methods, and targeted therapies.

Lung cancer is one of the most common causes of cancer-related death in the world. The large number of lung cancer cases is non-small cell lung cancer (NSCLC), which approximately accounting for 75% of lung cancer. Over the past years, our comprehensive knowledge about the molecular biology of NSCLC has been rapidly enriching, which has promoted the discovery of driver genes in NSCLC and directed FDA-approved targeted therapies. Of course, the targeted therapies based on driver genes provide a more exact option for advanced non-small cell lung cancer, improving the survival rate of patients. Now, we will review the landscape of driver genes in NSCLC including the characteristics, detection methods, the application of target therapy and challenges.

Precision medicine for hepatocellular carcinoma: driver mutations and targeted therapy.

Hepatocellular carcinoma (HCC) is the third most frequent cause of tumor-related mortality and there are an estimated approximately 850,000 new cases annually. Most HCC patients are diagnosed at middle or advanced stage, losing the opportunity of surgery. The development of HCC is promoted by accumulated diverse genetic mutations, which confer selective growth advantages to tumor cells and are called "driver mutations". The discovery of driver mutations provides a novel precision medicine strategy for late stage HCC, called targeted therapy. In this review, we summarized currently discovered driver mutations and corresponding signaling pathways, made an overview of identification methods of driver mutations and genes, and classified targeted drugs for HCC. The knowledge of mutational landscape deepen our understanding of carcinogenesis and promise future precision medicine for HCC patients.

Effect of Formaldehyde on the Heterogeneous Reaction of Nitrogen Dioxide on γ-Alumina.

Heterogeneous reactions of NO2 on various mineral aerosol particles have been investigated in many previous studies, but a fundamental understanding of how the adsorption of formaldehyde influences the heterogeneous reactions of NO2 remains unclear. In this work, the effect of formaldehyde preadsorption on heterogeneous reaction of NO2 on the surface of γ-Al2O3 at 298 K and ambient pressure was investigated by using diffuse reflectance infrared Fourier transform spectrometry (DRIFTS). It was found that the preadsorption of HCHO on γ-Al2O3 could suppress the formation of nitrate, and the rate of nitrate formation decreased with increasing amount of preadsorbed HCHO, whereas the following heterogeneous uptake of NO2 could suppress the hydration reaction of HCHO and promote the production of HCOO(-) during the reaction. Surface nitrite was formed and identified to be an intermediate product and gradually disappeared as the reaction proceeded. The amount of the formed nitrite decreased when the amount of HCHO increased. Uptake coefficients of heterogeneous reactions were calculated and found to be sensitive to the adsorption of HCHO. A possible mechanism for the influence of HCHO adsorption on the heterogeneous conversion of NO2 on γ-Al2O3 was proposed, and atmospheric implications based on these results were discussed.

Determination of fatty acids in soil samples by gas chromatography with mass spectrometry coupled with headspace solid-phase microextraction using a homemade sol-gel fiber.

Through the use of a homemade sol-gel-derived fiber, a headspace solid-phase microextraction technique coupled to gas chromatography with mass spectrometry was developed for the determination of fatty acids with long, even-numbered carbon chains (C12 -C24 ) in soil samples. The experimental parameters such as reaction time, temperature, and ionic strength that might affect derivatization, extraction, and desorption were investigated. Under the optimized conditions, the linearity of the method ranged from 0.1 to 100 mg/L with a correlation coefficient >0.997. The limit of detection values based on a signal-to-noise ratio of 3:1 were determined with the concentration from 0.39 to 39.4 µg/L. The recoveries of the method for the soil samples were from 91.15 to 108.1%. This developed method using a homemade fiber showed a higher sensitivity than that using a commercial polydimethylsiloxane fiber and was also for the analysis of real soil samples from the Paomaling geological park of China.