Background Central nervous system (CNS) involvement is recognized as a distinct manifestation of chronic GVHD (cGVHD). Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is an autoimmune disorder targeting the CNS. Therefore, the occasional detection of MOG antibodies in patients with CNS-cGVHD may represent a manifestation within the spectrum of CNS-GVHD.Case presentation A 22-year-old female with severe aplastic anemia (AA) underwent maternal haploidentical hematopoietic stem cell transplantation (HSCT) in May 2021. During conditioning, she developed acute neurotoxicity. Subsequent complications included acute and chronic GVHD as well as posterior reversible encephalopathy syndrome (PRES). Three months after transplantation, she developed sensory deficits and ataxia, and cervical magnetic resonance imaging revealed inflammatory lesions consistent with cervical myelitis. Comprehensive neuroimmunological evaluation excluded alternative infectious, metabolic, or neoplastic etiologies. Anti-myelin oligodendrocyte glycoprotein (MOG) antibodies were negative by cell-based assay (CBA) and tissue-based assay (TBA), but demonstrated weak, low-titer positivity on live-cell immunofluorescence. Neurological function recovered following treatment with intravenous immunoglobulin (IVIG) and methylprednisolone.Conclusions This case illustrates low-titer post-HSCT MOG seropositivity detected only by a live cell-based assay in a patient who fulfilled diagnostic criteria for CNS-GVHD. Live cell-based MOG testing may be considered in selected HSCT recipients with unexplained or atypical neuroinflammatory syndromes despite negative conventional assays, with results interpreted cautiously as hypothesis-generating for individualized immunosuppressive management.

Ferroptosis, a distinct form of regulated cell death, has attracted significant attention due to its critical role at the intersection of cellular metabolism, redox biology, and various human diseases. Macrophages play a key role in maintaining systemic iron balance, and their specific polarization states influence the regulation of ferroptotic processes. However, the therapeutic potential of ferroptosis in cancer is frequently limited by tumor-associated macrophages (TAMs), representing a significant challenge in applying immunotherapy to hematologic malignancies. Notably, inducing ferroptosis in macrophages themselves also holds therapeutic promise. This review synthesizes recent advances in macrophage ferroptosis research to clarify its role in disease pathogenesis. Importantly, we highlight the translational potential of the ferroptosis-TAM axis, suggesting that biomarker-guided modulation of this pathway, via novel nanocarriers or combination treatments, represents a paradigm-shifting strategy to overcome drug resistance and restore antitumor immunity in hematologic malignancies.

Acute lung injury (ALI) is a severe lung condition that can lead to acute respiratory failure. Given their anti-inflammatory and reparative properties, mesenchymal stem cells (MSCs) represent a promising therapeutic approach. This study aims to investigate the therapeutic potential and underlying mechanisms of interleukin-1 receptor antagonist (IL-1Ra) overexpressing MSCs (oeIL-1Ra-MSCs) in a murine ALI model. Following ALI induction, mice were treated with either oeIL-1Ra-MSCs or control MSCs (Mock-MSCs). The therapeutic effects on the lungs were evaluated using micro-CT, histopathology, and analysis of pro-inflammatory cytokines. Additionally, immunohistochemical and immunofluorescent analyses were performed on lung tissue, and mRNA sequencing was conducted to compare gene expression profiles between oeIL-1Ra-MSCs and Mock-MSCs. oeIL-1Ra-MSCs more effectively improved lung function in ALI mice, as evidenced by reduced patchy opacities, increased lung volume, decreased injury scores, and attenuated pulmonary edema. The treatment also significantly suppressed inflammation by decreasing pro-inflammatory cytokines and reducing macrophage and neutrophil infiltration. Furthermore, oeIL-1Ra-MSCs promoted tissue repair by enhancing the proliferation of alveolar type II epithelial (ATII) cells. mRNA sequencing identified elevated expression of insulin-like growth factor 2 (IGF2) in oeIL-1Ra-MSCs compared with Mock-MSCs. In vitro studies confirmed that IGF2 mediated the therapeutic effects partly by regulating the AKT/Bcl-2 and AKT/GSK-3β/Cyclin D1 signaling pathways, thereby inhibiting apoptosis and promoting the proliferation of ATII cells. In conclusion, IL-1Ra overexpression markedly enhances the therapeutic efficacy of MSCs in ALI by dual mechanisms: IL-1Ra secretion to counteract inflammation, and subsequent secretion of IGF2 to drive tissue regeneration, highlighting their strong potential for ALI.

Multiple myeloma (MM) is an incurable plasma cell malignancy. Dyskerin pseudouridine synthase 1 (DKC1), a nucleolar protein, is essential for RNA modification and cellular homeostasis, yet its role in MM remains unclear. Prognostic significance of DKC1 in MM patients was evaluated using the MMRF CoMMpass and GEO datasets. Functional effects of DKC1 knockdown or overexpression were investigated via in vitro proliferation, apoptosis assays and in vivo xenografts. Transcriptomic profiling and CMC-based pseudouridine (Ψ) mapping were used to define DKC1-mediated regulation of ATF5. Elevated DKC1 expression was identified as an independent prognostic marker of poor outcomes in MM patients. Decision tree analysis demonstrated that integrating DKC1 expression further refined prognostic stratification beyond the ISS system. Functional assays revealed that DKC1 promoted MM cell proliferation, survival and colony formation, while DKC1 knockdown or pharmacologic inhibition with pyrazofurin significantly reduced MM cell proliferation and colony formation, increased apoptosis in vitro, and suppressed tumor growth in xenograft models. RNA sequencing analysis identified ATF5 as a downstream target of DKC1, and subsequent experimental validation confirmed that DKC1 exerts part of its function through ATF5. We further demonstrated that DKC1 knockdown reduces ATF5 mRNA stability through impaired pseudouridylation. Site-specific Ψ modifications on ATF5 mRNA confirmed a direct post-transcriptional regulatory mechanism. DKC1 drives MM progression by promoting ATF5 stability through pseudouridylation, thereby enhancing myeloma cell proliferation and survival. These findings highlight that DKC1 may be used as a potential biomarker for risk stratification and a promising therapeutic target in MM.

TP53 mutations are associated with early progression and poor prognosis in diffuse large B cell lymphoma (DLBCL). This systematic review and meta-analysis evaluated remission outcomes of different therapies in TP53-mutated (TP53m) DLBCL. In total, 33,762 records were identified, and 31 studies comprising 1,164 patients with TP53m DLBCL were included. In the newly diagnosed (ND) setting, among patients treated with targeted therapy (TT) plus chemotherapy, the pooled complete remission (CR) rate was 60% (95% CI: 50%-69%; n = 552; I 2 = 75.7%) and the pooled overall remission rate (ORR) was 80% (95% CI: 74%-86%; n = 202; I 2 = 0%). In the relapsed/refractory (R/R) setting, among patients treated with chimeric antigen receptor T cell (CAR-T) therapy, the pooled CR rate was 39% (95% CI: 24%-54%; n = 139; I 2 = 64.2%) and the pooled ORR was 77% (95% CI: 43%-99%; n = 131; I 2 = 94.1%). TT plus chemotherapy and CAR-T-based therapy show encouraging activity in TP53-mutated DLBCL, but larger prospective studies are required to define their clinical roles.

BACKGROUND:This systematic review and network meta-analysis(NMA) comprehensively evaluated the efficacy and safety of non-first-line drugs in the treatment of adult patients with immune thrombocytopenia (ITP). RESEARCHDESIGN AND METHODS:PubMed, Web of Science, Embase, and the Cochrane Library were systematically searched. Randomized controlled trials (RCTs) investigating Count data were extracted in the form of event occurrences/non-occurrences. NMA was carried out via R. RESULTS:29 RCTs were encompassed. In contrast to placebo, the avatrombopag 20 mg group demonstrated the highest PR (RR = 12.23, 95% CrI: 5.48-33.72). The combination of eltrombopag and danazol exhibited the lowest incidence of bleeding events (RR = 0.31, 95% CrI: 0.16-0.57), while the avatrombopag 5 mg group had the lowest incidence of SAEs (RR = 0.44, 95% CrI: 0.22-0.84). The comprehensive evaluation suggested that romiplostim, initiated at a dose of 1 μg/kg within a dose-adjustment regimen, may confer one of the most favorable benefit - risk profiles, with a relatively high PR (SUCRA = 75.1%) and a low incidence of bleeding events (SUCRA = 54.8%). CONCLUSIONS:When initiating therapy with romiplostim at a dose of 1 μg/kg and subsequently titrating the dosage according to the patient's platelet response, romiplostim may represent one of the most effective therapeutic options. REGISTRATION:The study protocol for this systematic review was registered in the International Prospective Registry of Systematic Reviews (PROSPERO) database (http://www.crd.york.ac.uk/prospero/), and it was allocated the PROSPERO identification number.

Chronic myeloid leukemia (CML) is a hematological malignancy driven by diverse genetic aberrations, with the Philadelphia chromosome and its resultant BCR‑ABL1 fusion gene constituting key pathogenic drivers. Atypical BCR‑ABL1 fusion transcripts have distinctive structural and functional properties. Structural divergence in these variants leads to functional alterations of encoded oncoproteins, potentially influencing disease progression and therapeutic responsiveness. Conventional diagnostic modalities, including reverse transcription‑PCR and fluorescence in situ hybridization, may fail to detect rare variants, necessitating complementary high‑sensitivity techniques such as next‑generation sequencing). Tyrosine kinase inhibitors (TKIs), including imatinib and dasatinib, remain cornerstone treatments; however, marked inter‑variant heterogeneity in TKI responsiveness is observed: Patients harboring e13a3/e14a3 transcripts generally show favorable prognoses, while those with e1a3/e6a2 variants demonstrate an increased risk of relapse and/or TKI resistance, often requiring multimodal strategies combining chemotherapy or allogeneic hematopoietic stem cell transplantation. Although Chimeric Antigen Receptor)‑T cell therapy has shown promise in treating (Philadelphia chromosome‑positive B‑cell Acute Lymphoblastic Leukemia, its application in CML, particularly in variants such as e1a3 or e6a2, is not currently recommended as a first‑line treatment. Despite advances in elucidating the clinical implications of fusion gene heterogeneity in leukemogenesis, the prognostic value of atypical BCR‑ABL1 isoforms requires further validation through multicenter studies with extended cohorts. This review aimed to summarize cases of atypical fusion genes in CML, with analysis of clinical characteristics, therapeutic interventions, and prognostic outcomes, to provide clinicians with enhanced reference material for improved patient management.

Hemorrhagic cystitis (HC), a frequent complication of hematopoietic stem cell transplantation (HSCT), significantly affects quality of life and may worsen prognosis. Mesenchymal stem cells (MSCs) are known for their anti-inflammatory and tissue-regenerative properties. IL-1 receptor antagonist (IL-1Ra) blocks IL-1α and IL-1β by binding IL-1 receptors, offering potential therapeutic benefits. The aim of this study was to explore the therapeutic effect of MSCs overexpressing IL-1Ra on HC and investigate the underlying mechanisms. MSCs were isolated from human umbilical cord tissues, and IL-1Ra-overexpressing MSCs (oeIL-1Ra-MSCs) were generated using lentiviral transfections. HC was induced in rats by cyclophosphamide administration. Rats received tail vein injections of either oeIL-1Ra-MSCs or control MSCs (Mock-MSCs). Hematuria and bladder tissue changes were assessed using test strips and hematoxylin eosin (HE) staining. Immunohistochemistry detected molecular changes in bladder tissues. Gene expression differences between the two MSC groups were analyzed by mRNA sequencing and ChIP techniques. Treatment with oeIL-1Ra-MSCs significantly alleviated hematuria and reduced bladder edema and hemorrhage, and reduced mRNA expression levels of IL-1β, IL-6, and TNF-α in bladder tissues, compared with those in the Mock-MSC treatment group. Immunohistochemical staining showed a higher presence of CD105-positive cells (a marker for human MSCs) and CD31-positive vessels in bladder tissues treated with oeIL-1Ra-MSCs, indicating enhanced MSC migration and vascular stability. In vitro migration assay demonstrated a higher migration capacity of IL-1Ra overexpressing MSCs compared with that of control MSCs. Moreover, angiopoietin-1 (Ang-1) expression increased, while Angiopoietin-2 (Ang-2) expression decreased in bladder tissues treated with oeIL-1Ra-MSCs, suggesting enhanced blood vessel stabilization. Conditioned medium from oeIL-1Ra-MSC cultures stimulated human umbilical vein endothelial cell (hUVEC) migration, proliferation, and angiogenesis more effectively compared with that in control MSCs. mRNA sequencing revealed elevated HtrA3 expression in oeIL-1Ra-MSCs compared with that in control MSCs. Molecular analysis suggested that IL-1Ra overexpression in MSCs upregulated HtrA3 expression through inhibition of the JNK-c-Jun pathway and activation of the ERK–Egr-1 pathway. Overexpression of IL-1Ra significantly enhances the therapeutic efficacy of MSCs in HC by promoting MSC migration to damaged bladder tissues, suppressing inflammation, stabilizing blood vessels, and upregulating angiogenesis via activation of HtrA3 signaling pathways.

Lactate dehydrogenase A (LDHA) is highly expressed in various tumors. However, the role of LDHA in the pathogenesis of B-cell lymphoma remains unclear. Analysis of data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases revealed an elevated LDHA expression in diffuse large B-cell lymphoma (DLBC) tissues compared with normal tissues. Similarly, our results demonstrated a significant increase in LDHA expression in tumor tissues from the patients with B-cell lymphoma compared with those with lymphadenitis. To further elucidate potential roles of LDHA in B-cell lymphoma pathogenesis, we silenced LDHA in the Raji cells (a B-cell lymphoma cell line) using shRNA techniques. Silencing LDHA led to reduced mitochondrial membrane integrity, adenosine triphosphate (ATP) production, glycolytic activity, cell viability and invasion. Notably, LDHA knockdown substantially suppressed in vivo growth of Raji cells and extended survival in mice bearing lymphoma (Raji cells). Moreover, proteomic analysis identified feline sarcoma-related protein (FER) as a differential protein positively associated with LDHA expression. Treatment with E260, a FER inhibitor, significantly reduced the metabolism, proliferation and invasion of Raji cells. In summary, our findings highlight that LDHA plays multiple roles in B-cell lymphoma pathogenesis via FER pathways, establishing LDHA/FER may as a potential therapeutic target.

The plasma cell malignancy, multiple myeloma (MM), has significantly improved by the application of new drugs and autologous hematopoietic stem cell transplantation. However, MM remains incurable. A number of studies have revealed an anti‐MM effect of natural killer (NK) cells; however, their clinical efficacy is limited. Furthermore, glycogen synthase kinase (GSK)‐3β inhibitors show an antitumor function. In this study, we aimed to evaluate the potential roles of a GSK‐3β inhibitor (TWS119) in the regulation of NK cell cytotoxicity against MM. Our results showed that, in the presence of TWS119, the NK cell line, NK‐92, and in vitro‐expanded primary NK cells exhibited a significantly higher degranulation activity, expression of activating receptors, cellular cytotoxicity, and cytokine secretion when they were exposed to MM cells. Mechanistic studies indicated that TWS119 treatment markedly upregulated RAB27A expression, a key molecule for NK cell degranulation, and induced the colocalization of β‐catenin with NF‐κB in the nucleus of NK cells. More importantly, GSK‐3β inhibition combined with the adoptive transfer of TWS119‐treated NK‐92 cells significantly reduced tumor volume and prolonged the survival time of myeloma‐bearing mice. In summary, our novel findings suggest that targeting GSK‐3β through the activation of β‐catenin/NF‐κB pathway may be an important approach to improve therapeutic efficacy of NK cell transfusion for MM.

Background Gastric cancer (GC) is the fourth leading cause of cancer-related death worldwide. However, the precise mechanisms and specific biomarkers of GC have not been fully elucidated. We therefore sought to identify and validate the genes associated with GC. Methods RNA sequencing was performed on gastric tissue specimens from 10 cases each of non-atrophic gastritis (NAG), intestinal metaplasia (IM), and GC. Validation of gene expression was conducted through immunohistochemistry (IHC) staining. The Kaplan–Meier Plotter database was utilized to screen genes associated with prognosis, while protein–protein interaction analysis was conducted to identify hub genes. Results In GC-IM, the differentially expressed genes (DEGs) were predominantly enriched in pathways related to ECM-receptor interaction, focal adhesion, PI3K-Akt pathway, and pathways in cancer. Conversely, in IM-NAG, the DEGs were primarily enriched in pathways associated with fat digestion and absorption, pancreatic secretion, and retinol metabolism. IHC staining revealed elevated expression levels of KLK7 and KLK10 in GC. Specifically, KLK7 expression was found to be correlated with differentiation (P = 0.025) and depth of invasion (P = 0.007) in GC, while both KLK7 and KLK10 were associated with the overall survival (P < 0.05). Furthermore, a total of ten hub genes from DEGs in GC-NAG (COL6A2, COL1A1, COL4A1, COL1A2, SPARC, COL4A2, FN1, PCOLCE, SERPINH1, LAMB1) and five hub genes in IM-NAG (SI, DPP4, CLCA1, MEP1A, OLFM4) were demonstrated to have a significant correlation with the prognosis of GC. Conclusions The present study successfully identified and validated crucial genes associated with GC, providing valuable insights into the underlying mechanisms of this disease. The findings of this study have the potential to inform clinical practice.

A 58yearold woman presented with abdominal pain for over 7 months. Physical examination revealed macroglossia (figure 1) and severe tenderness of the periumbilical region. Laboratory investigation yielded elevated liver enzymes, hypoalbuminaemia, hyperlipidaemia, positive urine protein, brain natriuretic peptide 2520 pg/mL and cardiac troponin I 178 ng/L. Coagulation function was not markedly affected. Transthoracic echocardiogram showed left ventricular hypertrophy, diastolic dysfunction with normal left ventricular ejection fraction. Gastroscopy presented congestion, swelling, roughness and erosion of the gastric mucosa. Colonoscopy revealed rectal polyps. Abdominal CT and CT enterography demonstrated hepatosplenomegaly, renomegaly, dilation and effusion of the intestine and thickening of the ascending and transverse colonic wall (figure 2). Electromyography revealed that the skin sympathetic response amplitude of right upper limb was decreased, which indicated impaired peripheral and autonomic nervous system. Mesenteric CT angiography and bone marrow biopsy were normal.

Background: Leukemia is a cancer of the hematopoietic stem cells, which leads to an uncontrolled proliferation of leukocytes in blood. It is responsible for one of the most important cancer-associated deaths across the globe. Materials and Methods: In this study, we analyzed whether dieckol (DEK), a polyphenolic compound obtained from brown algae, can suppress cell proliferation via regulation of JAK/STAT3 signaling pathway in leukemia cell lines (Molt-4). Results: According to our results, DEK induced cytotoxicity, altered the cell morphology, caused nuclear damage, enhanced the formation of reactive oxygen species, decreased the production of mitochondrial membrane potential, reduced the levels of antioxidants (reduced glutathione, catalase, and superoxide dismutase), and augmented the level of thiobarbituric acid reactive substances in Molt-4 cell lines. Furthermore, STAT3 has been recognized as an important transcriptional mediator that controls cell proliferation. Thus, suppression of STAT3 transcription is a novel approach for the suppression of Molt-4 cell proliferation. In this study, DEK inhibited STAT3 translocation, thereby suppressing the increased expression of cyclin E1, PCNA, cyclin D1, and JAK1 in Molt-4 cell lines. Conclusion: In summary, DEK suppressed the cell proliferation of Molt-4 cells via inhibition of JAK/STAT3 signaling pathway.

OBJECTIVES: The coronavirus disease (COVID-19) outbreak has catastrophically threatened public health worldwide and presented great challenges for clinicians. To date, no specific drugs are available against severe acute respiratory syndrome coronavirus 2. Mesenchymal stem cells (MSCs) appear to be a promising cell therapy owing to their potent modulatory effects on reducing and healing inflammation-induced lung and other tissue injuries. The present pilot study aimed to explore the therapeutic potential and safety of MSCs isolated from healthy cord tissues in the treatment of patients with COVID-19. METHODS: Twelve patients with COVID-19 treated with MSCs plus conventional therapy and 13 treated with conventional therapy alone (control) were included. The efficacy of MSC infusion was evaluated by changes in oxygenation index, clinical chemistry and hematology tests, immunoglobulin (Ig) levels, and pulmonary computerized tomography (CT) imaging. The safety of MSC infusion was evaluated based on the occurrence of allergic reactions and serious adverse events. RESULTS: The MSC-treated group demonstrated significantly improved oxygenation index. The area of pulmonary inflammation decreased significantly, and the CT number in the inflammatory area tended to be restored. Decreased IgM levels were also observed after MSC therapy. Laboratory biomarker levels at baseline and after therapy showed no significant changes in either the MSC-treated or control group. CONCLUSION: Intravenous infusion of MSCs in patients with COVID-19 was effective and well tolerated. Further studies involving a large cohort or randomized controlled trials are warranted.

Add‐on devices have been widely used in clinical practice. The aim of this meta‐analysis was to compare the adenoma detection rate between Endocuff‐assisted colonoscopy (EAC) and cap‐assisted colonoscopy (CAC).

Background We aimed to investigate the anti-multiple myeloma (MM) activity of the new small molecular compound AE-848 (5-bromo-2-hydroxyisophthalaldehyde bis[(1-methyl-1H-benzimidazol-2-yl)hydrazone]) and its underlying anti-MM mechanism. Methods Cell viability and apoptosis were detected and quantified by using MTT and flow cytometry, respectively. JC-1 dye-related techniques were used to assess mitochondrial membrane potential (MMP). Western blotting was applied to detect the expression of NF-κB and PI3K/Akt/mTOR pathway-associated proteins. The in vivo activity of AE-848 against MM was evaluated in a MM mouse model. Results Application of AE-848 into the in vitro cell culture system significantly reduced the viability and induced apoptosis of the MM cell lines, RPMI-8226 and U266, in a dose- and time-dependent manner, respectively. JC-1 dye and Western blotting analysis revealed that AE-848 induced the cleavage of caspase-8, caspase-3, and poly ADP-ribose polymerase (PARP), resulting in loss of mitochondrial membrane potential (MMP). Both the NF-κB and PI3K/AKT/mTOR signaling pathways were involved in AE-848-induced apoptosis of U266 and RPMI8226 cells. Moreover, AE-848 leads to cell cycle arrest of MM cells. Its anti-MM efficacy was further confirmed in a xenograft model of MM. AE-848 administration significantly inhibited MM tumor progression and prolonged the survival of MM-bearing mice. More importantly, our results demonstrated that AE-848 markedly induced primary MM cell apoptosis. Conclusion Our results for the first time showed that the small compound AE-848 had potent in vitro and in vivo anti-myeloma activity, indicating that AE-848 may have great potential to be developed as a drug for MM treatment.

Background and Aims Add-on devices have been widely used in clinical practice. The aim of this meta-analysis was to compare the adenoma detection rate between Endocuff-assisted colonoscopy (EAC) and cap-assisted colonoscopy (CAC). Methods PubMed, EMBASE, SCOPUS, and Cochrane databases were searched. Outcomes included adenoma detection rate, cecal intubation rate, cecal intubation time, and withdrawal time. Dichotomous data were pooled to obtain the odds ratio or risk ratio. Continuous data were pooled using the mean difference. Results Of the 240 articles reviewed, six randomized controlled trials were included, with a total of 1994 patients. In the meta-analysis, no statistical difference in adenoma detection rate was detected between EAC and CAC (47.0%vs45.1%;P = 0.33). EAC significantly improved detection rate of diminutive adenomas/polyps compared with CAC (P = 0.01). Cecal intubation was achieved in 96.5% in EAC group and 97.9% in CAC group (P = 0.04). Besides, no statistical difference was found in cecal intubation time (P = 0.86), withdrawal time (P = 0.88), small adenomas/polyps (P = 0.60), or large adenomas/polyps (P = 0.95). Conclusion EAC and CAC have their respective merits. EAC significantly improve the detection of diminutive adenomas/polyps. CAC was better in cecal intubation rate.

Background. Multiple myeloma (MM) is one of the most common types of hematological malignancies, but its pathogenesis is poorly understood. Interleukin-9 (IL-9) is a growth factor, mainly produced by helper T cells. A series of observations suggested that IL-9 might act as a factor promoting oncogenesis. This study was aimed at detecting the serum concentrations of IL-9 in patients with MM, and to investigate its potential clinical significance. Methods. The serum IL-9 levels in 34 patients with MM and 15 normal controls were quantified by using the Enzyme Linked Immunosorbent Assay (ELISA). Results. Our results showed that the serum IL-9 concentration in MM patients was significantly higher than that in the controls (p<0.0001). Interestingly, the IL-9 level in serum was found to be negatively associated with the hemoglobin concentration among the newly diagnosed MM patients (p=0.0108, r=-0.5850). Moreover, MM patients with renal dysfunction showed a significant increase in serum IL-9 concentration over those with normal renal function (p=-0.0395). Conclusion. These findings may imply a novel role of IL-9 in anemia and/or renal dysfunction development in MM.

The present study aimed to investigate whether co-administration of mesenchymal stromal cells (MSC) and linezolid (LZD) into a rabbit model of methicillin-resistant Staphylococcus aureus (MRSA)-infected pneumonia would bring a synergistic therapeutic effect. Human umbilical cord-derived MSCs (hUMSCs) were isolated and characterized. A rabbit model of pneumonia was constructed by delivering 1 × 1010 CFU MRSA via a bronchoscope into the basal segment of lower lobe of right lung. Through analyzing vital sign, pulmonary auscultation, SpO2, chest imaging, bronchoscopic manifestations, pathology, neutrophil percentage, and inflammatory factors, we verified that a rabbit model of MRSA-induced pneumonia was successfully constructed. Individual treatment with LZD (50 mg/kg for two times/day) resulted in improvement of body weight, chest imaging, bronchoscopic manifestations, histological parameters, and IL-10 concentration in plasma (P<0.01), decreasing pulmonary auscultation, and reduction of IL-8, IL-6, CRP, and TNF-α concentrations in plasma (P<0.01) compared with the pneumonia model group at 48 and 168 h. Compared with LZD group, co-administration of hUMSCs (1 × 106/kg for two times at 6 and 72 h after MRSA instillation) and LZD further increased the body weight (P<0.05). The changes we observed from chest imaging, bronchoscopic manifestations and pathology revealed that co-administration of hUMSCs and LZD reduced lung inflammation more significantly than that of LZD group. The plasma levels of IL-8, IL-6, CRP, and TNF-α in combined group decreased dramatically compared with the LZD group (P<0.05). In conclusion, hUMSCs administration significantly improved therapeutic effects of LZD on pneumonia resulted from MRSA infection in a rabbit model.

Question: A 13-year-old boy presented with recurrent melena for 10 years accompanied with dizziness and fatigue. This patient had no history of nonsteroidal anti-inflammatory drug use, peptic ulcer, or chronic liver disease, and no family history of gastrointestinal bleeding. He was born with a right foot hemangioma that was resected when he was 2 years old. Additionally, he had received multiple blood transfusions for iron deficiency anemia since childhood. The body mass index was 16.5 kg/m2 and physical examination revealed active bowel sounds. Laboratory examinations showed severe iron deficiency anemia (the lowest hemoglobin available was 36 g/L) and positive stool occult blood. Gastroscopy unveiled superficial gastritis and colonoscopy was normal. Second-look examinations showed the same results. No clinically important signs were observed on computed tomography scan. Given these results, small intestinal bleeding was considered. Therefore, a video capsule endoscopy (VCE) was carried out and revealed multifocal hemangioma-like purplish blue lesions in jejunum and ileum (Figure A). Then a single-balloon enteroscopy (SBE) was performed, which showed multifocal vascular lesions ranging between 1.0 and 2.0 cm in the jejunum and ileum (Figure B, C). Based on these findings, what is your diagnosis? What is the next step in management for this patient? Look on page 312 for the answer and see the Gastroenterology website (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and images in GI. Based on the history of hemangioma resection and vascular lesions in small intestine, along with typical manifestations of chronic gastrointestinal bleeding, diagnosis of blue rubber bleb nevus syndrome (BRBNS) was made. According to American College of Gastroenterology Clinical Guideline,1Gerson L.B. Fidler J.L. Cave D.R. et al.ACG clinical guideline: diagnosis and management of small bowel bleeding.Am J Gastroenterol. 2015; 110 (; quiz 1288): 1265-1287Crossref PubMed Scopus (357) Google Scholar for patients with recurrence of small bowel bleeding, endoscopic management could be considered depending on the patient's clinical course and response to prior therapy. Consequently, injections of lauromacrogol with SBE were applied (Figure D). Lesions that ranged from 1 to 2 cm was injected with 1–2 mL lauromacrogol until the mucosa turned white. Three SBEs had been performed in a 5-month period. A total of 20 lesions were successfully treated with lauromacrogol. The treated hemangiomas became small and the site healed 5 months later after treatment (Figure E, F). The patient has been followed for 1 year and he remains in good clinical condition with latest hemoglobin level at 110 g/L. No further blood transfusion is needed. BRBNS is a rare disorder characterized by discrete venous malformations of varying size and appearance that are present on the skin and within the gastrointestinal tract.2Felton S.J. Ferguson J.E. Multiple cutaneous swellings associated with sudden collapse.JAMA. 2012; 308: 1685-1686Crossref PubMed Scopus (2) Google Scholar With more widely application of VCE and the increase of image resolution, the detection rate and the diagnostic accuracy of BRBNS are significantly improved. Treatment of BRBNS varies depending on the site, size, and number of lesions. Medication, surgery, and endoscopic therapy are currently clinically applied. The successful use of sirolimus was recently reported in the treatment of vascular lesions.3Yuksekkaya H. Ozbek O. Keser M. et al.Blue rubber bleb nevus syndrome: successful treatment with sirolimus.Pediatrics. 2012; 129: e1080-e1084Crossref PubMed Scopus (106) Google Scholar However, sirolimus has potential adverse effects on renal function, bone marrow, and cholesterol metabolism. In consideration of the patient's young age, we did not adopt this method. Surgical resection is more suitable for limited or life-threatening lesions. The lesions in this patient were mild and sporadic. Consequently, in this case, endoscopic injection of lauromacrogol was performed. This was the most complicated case of endoscopic treatment of BRBNS in our center, which proved lauromacrogol injection a feasible approach. Through a literature review, lauromacrogol has been used for treatment of vascular lesions for decades. However, there is still no standard instruction for the dosage of lauromacrogol. We hope that our experience would be a reference for the endoscopic treatment of BRBNS.