Waldenström macroglobulinemia (WM) is a B-cell lymphoproliferative disease characterized by IgM monoclonal gammopathy and bone marrow (BM) infiltration caused by lymphoplasmacytic lymphoma. The MYD88 L265P variant is present in > 90% of WM cases.We used droplet digital PCR (ddPCR) to detect MYD88 L265P in initial BM samples from 15 patients with WM and assessed the implication of variant burden as a tumor load and prognostic marker. MYD88 L265P burden correlated with clinical indicators, including peripheral blood and BM lymphocyte percentages (P < 0.001 and P = 0.003, respectively), serum lactate dehydrogenase level (P = 0.045), and platelet count (P = 0.003). Patients classified into intermediate and high groups according to the Revised International Prognostic Score System for WM had higher MYD88 L265P copies/μL than patients in very low and low groups (P = 0.017), as had patients with minor response or stable disease after primary treatment than those with complete, partial, or very good partial response (P = 0.034).MYD88 L265P burden correlates well with multiple clinical indicators and has prognostic relevance, making it a potential marker for assessing tumor burden and predicting prognosis in WM.

Measurable residual disease (MRD) testing, a standard procedure in B-lymphoblastic leukemia (B-ALL) diagnostics, is assessed using multiparametric flow cytometry (MFC) and next-generation sequencing (NGS) analysis of immunoglobulin gene rearrangements. We evaluated the concordance between eight-color, two-tube MFC-MRD the LymphoTrack NGS-MRD assays using 139 follow-up samples from 54 pediatric patients with B-ALL. We also assessed the effect of hemodilution in MFC-MRD assays. The MRD-concordance rate was 79.9% (N = 111), with 25 (18.0%) and 3 (2.2%) samples testing positive only by NGSMRD (MFC − NGS + MRD) and MFC-MRD (MFC + NGS − MRD), respectively. We found a significant correlation in MRD values from total nucleated cells between the two methods (r = 0.736 [0.647–0.806], P < 0.001). The median MRD value of MFC − NGS + MRD samples was estimated to be 0.0012% (0.0001%–0.0263%) using the NGS-MRD assays. Notably, 14.3% of MFC − NGS + MRD samples showed NGS-MRD values below the limit of detection in the MFC-MRD assays. The percentages of hematogones detected in MFC-MRD assays significantly differed between the discordant and concordant cases (P < 0.001). MFC and NGS-MRD assays showed relatively high concordance and correlation in MRD assessment, whereas the NGS-MRD assay detected MRD more frequently than the MFC-MRD assay in pediatric B-ALL. Evaluating the hematogone percentages can aid in assessing the impact of sample hemodilution.

Purpose: To evaluate the therapeutic effect of repeated injections of mesenchymal stem cell (MSC)-derived exosomes on the erectile dysfunction (ED) of bilateral cavernous nerve injury (BCNI) rat model and to identify potential target genes of these injections. Materials and Methods: MSC-derived exosomes were isolated using an aqueous two-phase system. Rats were randomly assigned into four groups: Normal, BCNI, exosome once, and exosome-repeat groups. After four weeks, we measured the intracavernosal pressure (ICP)/mean arterial pressure (MAP) ratio to evaluate erectile function and examined cavernous nerve tissues for histological and molecular analyses. RNA sequencing in penile tissues was used to determine differentially expressed genes and was verified by quantitative polymerase chain reaction. Human umbilical vein endothelial cells (HUVECs) were used for in vitro studies to analyze biological roles. Results: The ICP/MAP ratios in the exosome-once and exosome-repeat groups were significantly increased compared to those in the BCNI group. Interestingly, the ICP/MAP ratio showed a greater increase in the exosome-repeat group, which also showed significantly increased smooth muscle/collagen ratio, α-smooth muscle actin and neuronal nitric oxide synthase expression, and cyclic guanosine monophosphate level compared to the BCNI and exosome-once groups. Three genes were significantly differentially expressed in the exosome group, among which Ras homolog family member B promoted cell proliferation and angiogenesis of HUVECs. Conclusions Repeated injections of MSC-derived exosomes can be effective in the treatment of rat models with ED induced by cavernous nerve injury.

Purpose: To evaluate the therapeutic effect of repeated injections of mesenchymal stem cell (MSC)-derived exosomes on the erectile dysfunction (ED) of bilateral cavernous nerve injury (BCNI) rat model and to identify potential target genes of these injections. Materials and Methods: MSC-derived exosomes were isolated using an aqueous two-phase system. Rats were randomly assigned into four groups: Normal, BCNI, exosome once, and exosome-repeat groups. After four weeks, we measured the intracavernosal pressure (ICP)/mean arterial pressure (MAP) ratio to evaluate erectile function and examined cavernous nerve tissues for histological and molecular analyses. RNA sequencing in penile tissues was used to determine differentially expressed genes and was verified by quantitative polymerase chain reaction. Human umbilical vein endothelial cells (HUVECs) were used for in vitro studies to analyze biological roles. Results: The ICP/MAP ratios in the exosome-once and exosome-repeat groups were significantly increased compared to those in the BCNI group. Interestingly, the ICP/MAP ratio showed a greater increase in the exosome-repeat group, which also showed significantly increased smooth muscle/collagen ratio, α-smooth muscle actin and neuronal nitric oxide synthase expression, and cyclic guanosine monophosphate level compared to the BCNI and exosome-once groups. Three genes were significantly differentially expressed in the exosome group, among which Ras homolog family member B promoted cell proliferation and angiogenesis of HUVECs. Conclusions Repeated injections of MSC-derived exosomes can be effective in the treatment of rat models with ED induced by cavernous nerve injury.

Purpose: To evaluate the therapeutic effect of repeated injections of mesenchymal stem cell (MSC)-derived exosomes on the erectile dysfunction (ED) of bilateral cavernous nerve injury (BCNI) rat model and to identify potential target genes of these injections. Materials and Methods: MSC-derived exosomes were isolated using an aqueous two-phase system. Rats were randomly assigned into four groups: Normal, BCNI, exosome once, and exosome-repeat groups. After four weeks, we measured the intracavernosal pressure (ICP)/mean arterial pressure (MAP) ratio to evaluate erectile function and examined cavernous nerve tissues for histological and molecular analyses. RNA sequencing in penile tissues was used to determine differentially expressed genes and was verified by quantitative polymerase chain reaction. Human umbilical vein endothelial cells (HUVECs) were used for in vitro studies to analyze biological roles. Results: The ICP/MAP ratios in the exosome-once and exosome-repeat groups were significantly increased compared to those in the BCNI group. Interestingly, the ICP/MAP ratio showed a greater increase in the exosome-repeat group, which also showed significantly increased smooth muscle/collagen ratio, α-smooth muscle actin and neuronal nitric oxide synthase expression, and cyclic guanosine monophosphate level compared to the BCNI and exosome-once groups. Three genes were significantly differentially expressed in the exosome group, among which Ras homolog family member B promoted cell proliferation and angiogenesis of HUVECs. Conclusions Repeated injections of MSC-derived exosomes can be effective in the treatment of rat models with ED induced by cavernous nerve injury.

Purpose: To evaluate the therapeutic effect of repeated injections of mesenchymal stem cell (MSC)-derived exosomes on the erectile dysfunction (ED) of bilateral cavernous nerve injury (BCNI) rat model and to identify potential target genes of these injections. Materials and Methods: MSC-derived exosomes were isolated using an aqueous two-phase system. Rats were randomly assigned into four groups: Normal, BCNI, exosome once, and exosome-repeat groups. After four weeks, we measured the intracavernosal pressure (ICP)/mean arterial pressure (MAP) ratio to evaluate erectile function and examined cavernous nerve tissues for histological and molecular analyses. RNA sequencing in penile tissues was used to determine differentially expressed genes and was verified by quantitative polymerase chain reaction. Human umbilical vein endothelial cells (HUVECs) were used for in vitro studies to analyze biological roles. Results: The ICP/MAP ratios in the exosome-once and exosome-repeat groups were significantly increased compared to those in the BCNI group. Interestingly, the ICP/MAP ratio showed a greater increase in the exosome-repeat group, which also showed significantly increased smooth muscle/collagen ratio, α-smooth muscle actin and neuronal nitric oxide synthase expression, and cyclic guanosine monophosphate level compared to the BCNI and exosome-once groups. Three genes were significantly differentially expressed in the exosome group, among which Ras homolog family member B promoted cell proliferation and angiogenesis of HUVECs. Conclusions Repeated injections of MSC-derived exosomes can be effective in the treatment of rat models with ED induced by cavernous nerve injury.

Purpose: To evaluate the therapeutic effect of repeated injections of mesenchymal stem cell (MSC)-derived exosomes on the erectile dysfunction (ED) of bilateral cavernous nerve injury (BCNI) rat model and to identify potential target genes of these injections. Materials and Methods: MSC-derived exosomes were isolated using an aqueous two-phase system. Rats were randomly assigned into four groups: Normal, BCNI, exosome once, and exosome-repeat groups. After four weeks, we measured the intracavernosal pressure (ICP)/mean arterial pressure (MAP) ratio to evaluate erectile function and examined cavernous nerve tissues for histological and molecular analyses. RNA sequencing in penile tissues was used to determine differentially expressed genes and was verified by quantitative polymerase chain reaction. Human umbilical vein endothelial cells (HUVECs) were used for in vitro studies to analyze biological roles. Results: The ICP/MAP ratios in the exosome-once and exosome-repeat groups were significantly increased compared to those in the BCNI group. Interestingly, the ICP/MAP ratio showed a greater increase in the exosome-repeat group, which also showed significantly increased smooth muscle/collagen ratio, α-smooth muscle actin and neuronal nitric oxide synthase expression, and cyclic guanosine monophosphate level compared to the BCNI and exosome-once groups. Three genes were significantly differentially expressed in the exosome group, among which Ras homolog family member B promoted cell proliferation and angiogenesis of HUVECs. Conclusions Repeated injections of MSC-derived exosomes can be effective in the treatment of rat models with ED induced by cavernous nerve injury.