Early M-protein immune reconstitution after autologous haematopoietic stem cell transplantation is a good prognostic marker for patients with high-risk cytogenetic multiple myeloma.

The presence of transient abnormal protein banding (M-protein immune reconstitution) in serum immunofixation electrophoresis after autologous haematopoietic stem cell transplantation in patients with multiple myeloma has been reported. The purpose of this study was to investigate the impact of post-transplant M-protein immune reconstitution on the prognosis of patients with multiple myeloma. M-protein immune reconstitution was observed in 25.9% (75/290) of patients. The CR rate and MRD negativity were higher in the M-protein immune reconstitution group (85.3% vs. 69.3%, p = 0.013, 81.9% vs. 66.5%, p = 0.014). Although there were no significant differences between the groups, the overall median survival time was longer in the M-protein immune reconstruction group (80 vs. 72 m, p = 0.076; not reached vs. 105 m, p = 0.312). Among patients in the cytogenetic high-risk group, the occurrence of M-protein immune reconstitution predicted better PFS and OS (80 vs. 31 m, p = 0.010; not reached vs. 91 m, p = 0.026). Additionally, in revised-International Staging System stage III patients, PFS and OS were better in those who achieved M-protein immune reconstitution (80 vs. 20 m, p = 0.025; 57 vs. 32 m, p = 0.103). The better prognosis of M-protein immune reconstitution patients may be associated with the acquisition of a deeper response. In high-risk patients, early acquisition of M-protein immune reconstitution may suggest a better prognosis.

Two-Photon Cellular and Intravital Imaging of Hypochlorous Acid by Fluorescent Probes That Exhibit a Synergistic Excited-State Intramolecular Proton Transfer-Intramolecular Charge Transfer Mechanism Enabling Near-Infrared Emission with a Large Stokes Shift.

To develop highly effective molecular tools for intravital imaging of hypochlorous acid (HOCl), in this study, we initially designed two-photon hybrid fluorophores, SDP and P-SDP, by conjugating the classical dye 2-(2'-hydroxyphenyl)benzothiazole with the two-photon hydroxylphenyl-butadienylpyridinium fluorophore. The designed fluorophores exhibit a synergistic interaction between excited-state intramolecular proton transfer and intramolecular charge transfer mechanisms, enabling near-infrared (NIR) emission and significant Stokes shifts. Subsequently, using these fluorophores, we developed two HOCl fluorescent probes, SDP-SN and P-SDP-SN, by further incorporating N,N-dimethylthiocarbamate as a specific recognition group for HOCl. Toward HOCl, both SDP-SN and P-SDP-SN demonstrate an ultrafast response (less than 3 s), NIR emission at wavelengths of 714 and 682 nm, and remarkable Stokes shifts of 303 and 271 nm, respectively. Leveraging these advantages in conjunction with their ability to cross the blood-brain barrier, the probes find successful application in two-photon cellular and intravital imaging of HOCl. This includes visualizing endogenous generation of HOCl in cellular models related to inflammation, hyperglycemia, and ferroptosis, as well as mapping in vivo generation of HOCl within the brain and abdominal cavity using a murine model of systemic inflammation.

GHS-R1a deficiency protects against lipopolysaccharide-induced spatial memory impairment in mice.

Neuroinflammation has been implicated in cognitive deficits of neurological and neurodegenerative diseases. There is abundant evidence that the application of ghrelin, an orexigenic hormone regulating appetite and energy balance, abrogates neuroinflammation and rescues associated memory impairment. However, the underlying mechanism is uncertain. In this study, we find that both intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administration of lipopolysaccharide (LPS) impairs spatial memory in mice. LPS treatment causes neuroinflammation and microglial activation in the hippocampus. Ghsr1a deletion suppresses LPS-induced microglial activation and neuroinflammation, and rescued LPS-induced memory impairment. Our findings thus suggest that GHS-R1a signaling may promote microglial immunoactivation and contribute to LPS-induced neuroinflammation. GHS-R1a may be a new therapeutic target for cognitive dysfunction associated with inflammatory conditions.

Efficacy of prophylactic antibiotics for the prevention of neutropenic fever in patients with multiple myeloma receiving high-dose cyclophosphamide for stem cell mobilization.

High-dose cyclophosphamide (HD-Cy) (3 g/m2) plus granulocyte colony-stimulating factor (G-CSF) is a very effective regimen for peripheral blood stem cell (PBSC) mobilization. Unfortunately, it is associated with an increased risk of neutropenic fever (NF). We analyzed the effect of NF on PBSC apheresis results and the efficacy of prophylactic antibiotics for the prevention of NF associated with HD-Cy plus G-CSF for PBSC mobilization in patients with newly diagnosed multiple myeloma (MM). First, patients were divided into NF ( +) and NF ( -) groups according to whether they suffered from NF during mobilization. Second, we divided patients into an antibiotic prophylaxis group and a nonantibiotic prophylaxis group according to whether antibiotic prophylaxis was used during the mobilization period. Our study showed that NF( +) patients (n = 44) had lower CD34 + cell dose collection (median 2.60 versus 5.34 × 106/kg, P < 0.001) and slower neutrophil engraftment and platelet engraftment (median 11 versus 10 days, P = 0.002, and median 13 versus 11 days, P = 0.043, respectively) than NF( -) patients (n = 234). Of note, the nonantibiotic prophylaxis group patients (n = 30) had a 26.7% incidence of NF. In the patients receiving antibiotic prophylaxis (n = 227), the incidence was reduced to 9.3% (P = 0.01). The antibiotic prophylaxis patients had higher CD34 + cell collection (median 5.41 versus 2.27 × 106/kg, P < 0.001) and lower hospitalization cost of mobilization ($ median 3108.02 versus 3702.39, p = 0.012). Thus, our results demonstrate that NF is associated with lower CD34 + cell collection and that antibiotic prophylaxis can reduce the incidence of NF and improve stem cell mobilization and collection outcomes, which reduces the hospitalization cost of mobilization.

Dermotoscope assisted diagnosis of adolescent bullous pilomatricoma: six case reports.

BACKGROUND: Pilomatricoma (PM) is a cutaneous benign neoplasm derived from the hair matrix. It clinically presents as a solitary and firm nodule overlying normal epidermis and is usually not easy to be noticed at early stage. Nevertheless, when special bullous lesion occurs in a short time or even ulcerates, preoperative diagnosis by a dermatologist is often challenging especially when the pediatric patients refuse biopsy. CASE PRESENTATION: We present six bullous PM cases and particularly conduct correlation analysis on the dermotoscopy and histopathology detection data. The basic information, medical history, symptoms and lesion morphology results of the patients were also provided. We found that the incidence of bullous PM was higher in females than in males, and most patients were adolescents and the predilection location seem to be consistent in the vaccine injection site. The dermatoscopic features of bullous PM reported were luminous yellow structure below, with gray-blue homogeneous areas and branched capillary. The histological features were consistent with PM, and evident epidermis bullae were above the tumor with extraordinary dilation of lymphangion in the upper dermis. The patients described in this study were Chinese patients in Han population included 4 females and 2 males, coincidentally, they are almost teen-age, respectively are 5,11,17,19,21,22 year-old. CONCLUSIONS: This study reported and analyzed the dermotoscopy and clinical characteristics of bullous PM, dermotoscopy may guide as a rapid and reliable technique in bullous PM diagnosis.

SCUBE1 Promotes Gestational Diabetes Mellitus: A Bioinformatics and Experimental Investigation.

Gestational diabetes mellitus (GDM) is one of the most common metabolic diseases in pregnant women, posing significant risks to the life and health of both mothers and fetuses. With improving living standards, the incidence of GDM is increasing rapidly. Therefore, understanding the underlying mechanism of GDM is of paramount importance. We downloaded two datasets from the Gene Expression Omnibus (GEO) database, containing sequencing data specifically related to "gestational diabetes" and "placenta". By merging these two datasets, a mRNA expression dataset was obtained and subjected to bioinformatics analyses. To screen out corresponding genes, differential analysis and weighted correlation network analysis (WGCNA) were carried out. Lasso, support vector machine and random forest analyses were subsequently performed for identifying key genes from the differentially expressed genes (DEGs) jointly screened out through differential analysis and WGCNA. Afterwards, immunoinfiltration and correlation analysis were performed to screen immune cells that play a role in disease progression and explore the correlation between the screened key genes and immune cells, after which Western Blot, quantitative real-time polymerase chain reaction, Immunohistochemistry, methyl thiazolyl tetrazolium, flow cytometry, scratch and Transwell assays were, respectively, performed for verification. For further verification, we found that the expression levels of MAP6D1 and SCUBE1 in embryonic tissues of GDM patients was higher compared to those of healthy pregnant women, which was consistent with the results of bioinformatics analysis. Consequently, SCUBE1 was selected for follow-up experiment. In order to explore the role of SCUBE1 in the development of GDM, we treated the trophoblastic cells HTR-8/SVneo with high glucose, and on this basis downregulated the expression of SCUBE1. Through further analysis, we observed that SCUBE1 had a role in reducing cell activity, migration and invasion, and promoting cell apoptosis. In summary, SCUBE1 promotes the development of GDM by increasing cell apoptosis and reducing cell activity, migration, and invasion.

Cellular and Intravital Imaging of NAD(P)H by a Red-Emitting Quinolinium-Based Fluorescent Probe that Features a Shift of Its Product from Mitochondria to the Nucleus.

NAD(P)H is a vital hydrogen donor and electron carrier involved in numerous biological processes. The development of small-molecule tools for intravital imaging of NAD(P)H is significant for further exploring their pathophysiological roles. Herein, we rationally designed a fluorescent probe NADH-R by a simple graft of pyridiniumylbutenenitrile on a 1-methylquinolinium moiety in the 3-position. Benefited from the reduction of quinolinium by NAD(P)H, this probe releases the free push-pull fluorophore NADH-RH, allowing a turn-on red-emitting fluorescence response together with an ultralow detection limit of 12 nM. Under the assistance of the probe, we first monitored exogenous and endogenous generation of NAD(P)H in living cells, subsequently observed dynamic changes of NAD(P)H levels in living cells under different metabolic perturbations, and finally visualized the declined NAD(P)H levels in live mouse brain in a stroke model. Unexpectedly, the time-dependent colocalization experiment revealed that the probe reacts with mitochondrial NAD(P)H, followed by a shift of its reduced product NADH-RH from mitochondria to the nucleus, highlighting that NADH-RH is a novel nucleus-directed dye scaffold, which would facilitate the development of nucleus-targeting fluorescent probes and drugs.

Clinical significance of flow cytometry in detection of minimal residual disease in cerebrospinal fluid. / è„‘è„Šæ¶²æµå¼ç»†èƒžæœ¯æ£€æµ‹å¾®å°æ®‹ç•™ç— çš„ä¸´åºŠæ„ä¹‰.

OBJECTIVES: Central nervous system leukemia (CNSL) is one of the main causes of recurrence and death in patients with acute leukemia. This study aims to dynamically monitor minimal residual disease (MRD) in cerebrospinal fluid and bone marrow of patients with different types of acute leukemia by flow cytometry (FCM), and to compare the timeliness and consistency of MRD detection between the 2 methods to further explore the application value of monitoring MRD in cerebrospinal fluid. METHODS: A total of 199 patients with acute leukemia admitted to the Guangdong Provincial people's Hospital between October 2018 and January 2022 were retrospectively analyzed, and multiparametric FCM method was adopted to summarize and analyze MRD in cerebrospinal fluid of patients with different types of leukemia and MRD in cerebrospinal fluid and bone marrow specimens of the same patients, and its role in assessing the prognostic value of patients was discussed. RESULTS: Among the 199 acute leukemia cases, a total of 31 cases (15.58%) were positive MRD in the cerebrospinal fluid, of which 18 cases (58%) were detected earlier than the corresponding bone marrow specimens. Among the 19 patients with acute T lymphoblastic leukemia, 134 patients with acute B lymphoblastic leukemia, and 46 patients with acute myeloid leukemia counted, there were 4, 18, and 9 patients with positive MRD in the cerebrospinal fluid. The Kappa value of the concordance test between the results of cerebrospinal fluid MRD and bone marrow MRD in different types of acute leukemia was only 0.156, demonstrating a low concordance between them. CONCLUSIONS: Dynamic monitoring of cerebrospinal fluid MRD by FCM can be used as a monitoring index for central nervous system leukemia, and monitoring cerebrospinal fluid can detect MRD earlier compared with bone marrow, which complements each other as a sensitive index for evaluating prognosis with significant guidance in clinic.

Lymphoepithelioma-like neoplasm of the biliary tract with 'probable low malignant potential'.

AIMS: Lymphoepithelioma-like carcinomas (LELCs) are uncommon epithelial cancers characteristically showing two distinct components consisting of malignant epithelial cells and prominent dense lymphoid infiltrate. Hepatic LELCs consist of two types, the lymphoepithelioma-like hepatocellular carcinoma and lymphoepithelioma-like cholangiocarcinoma (LEL-CCA), with the latter being strongly associated with Epstein-Barr virus (EBV). METHODS AND RESULTS: We present a series of three cases of intrahepatic biliary EBV-associated LEL tumours in which the biliary epithelial component showed a distinctly benign appearance, instead of the usual malignant epithelial features of a typical CCA or EBV-associated LEL-CCA. In the lesions, the biliary epithelium showed interconnecting glands or cords of cells. All had a very low proliferation (Ki-67) index. Immunohistochemistry for IDH1 and TP53 performed on two cases was negative and molecular tests for EGFR and KRAS gene mutations performed on one were negative. Prognosis was very good in all three cases, with patients alive with no evidence of disease 24-62 months after surgery. Intriguingly, all three cases had co-infection of HBV and EBV. These cases are also discussed in the context of the 63 cases of LEL-CCA available in the literature, with a focus on epidemiology, clinicopathological features and potential research interests. CONCLUSIONS: Based on the distinct clinicopathological features and unique survival benefits, we believe these tumours represent the benign end of the spectrum of EBV-associated lymphoepithelial biliary carcinomas. Whether these tumours require a revision of the current nomenclature to 'lymphoepithelioma-like neoplasm of the biliary tract with probable low malignant potential' will require more detailed analysis with larger case-series.

Irisin as a predictor of bone metabolism in Han Chinese Young Men with pre-diabetic individuals.

BACKGROUND: Irisin is a novel myokine both in mice and humans, and it can also be secreted by adipose tissue and the liver in a small amounts. There are few studies on irisin and bone metabolism. The aim of this study was to assess the relationship between serum irisin levels and bone metabolism and analyze its related factors in Han young male with pre-diabetic individuals. METHODS: This cross-sectional study included 41 pre-diabetes and 45 normal glucose tolerance (NGT). Anthropometric measurements, including height, weight, waist circumference (WC), and bone mineral content (BMC), were performed. All patients underwent an oral glucose tolerance test (OGTT) after 8 h of fasting, and the levels of glucose, insulin, lipids, serum irisin and bone turnover markers were measured. RESULTS: The levels of serum irisin (4.4 ± 1.4 vs. 6.3 ± 1.5 µg/mL), P1NP and OC were significantly lower and CTX was significantly higher in the pre-diabetes group (P < 0.05). BMC did not differ in the two groups (P > 0.05). Serum irisin levels negatively correlated with BMI (r =-0.325), FPG (r =-0.329), TG (r =-0.339) (P < 0.05) in NGT individuals. Serum irisin levels positively correlated with P1NP (r = 0.398), OC (r = 0.351), HDL-C (r = 0.432) and negatively correlated with FPG (r = -0.725), 2 h-PG (r = -0.360) (P < 0.05) in pre-diabetic individuals. Multiple regression analysis revealed that Serum irisin (ß = 9.768, P = 0.025) and WC (ß = -2.355, P = 0.002) were significant independent predictors for P1NP. CONCLUSION: Bone turnover markers were changed rather than bone mineral content in young men with pre-diabetes. In pre-diabetes individuals, serum irisin levels were reduced and close relationship with P1NP. Falling irisin levels may be a predictor of decreased bone formation in Han young men with pre-diabetes individuals.

Wnt/ß-Catenin Signaling Pathway Is Strongly Implicated in Cadmium-Induced Developmental Neurotoxicity and Neuroinflammation: Clues from Zebrafish Neurobehavior and In Vivo Neuroimaging.

Cadmium (Cd) is a toxic heavy metal and worldwide environmental pollutant which seriously threatens human health and ecosystems. It is easy to be adsorbed and deposited in organisms, exerting adverse effects on various organs including the brain. In a very recent study, making full use of a zebrafish model in both high-throughput behavioral tracking and live neuroimaging, we explored the potential developmental neurotoxicity of Cd2+ at environmentally relevant levels and identified multiple connections between Cd2+ exposure and neurodevelopmental disorders as well as microglia-mediated neuroinflammation, whereas the underlying neurotoxic mechanisms remained unclear. The canonical Wnt/ß-catenin signaling pathway plays crucial roles in many biological processes including neurodevelopment, cell survival, and cell cycle regulation, as well as microglial activation, thereby potentially presenting one of the key targets of Cd2+ neurotoxicity. Therefore, in this follow-up study, we investigated the implication of the Wnt/ß-catenin signaling pathway in Cd2+-induced developmental disorders and neuroinflammation and revealed that environmental Cd2+ exposure significantly affected the expression of key factors in the zebrafish Wnt/ß-catenin signaling pathway. In addition, pharmacological intervention of this pathway via TWS119, which can increase the protein level of ß-catenin and act as a classical activator of the Wnt signaling pathway, could significantly repress the Cd2+-induced cell cycle arrest and apoptosis, thereby attenuating the inhibitory effects of Cd2+ on the early development, behavior, and activity, as well as neurodevelopment of zebrafish larvae to a certain degree. Furthermore, activation and proliferation of microglia, as well as the altered expression profiles of genes associated with neuroimmune homeostasis triggered by Cd2+ exposure could also be significantly alleviated by the activation of the Wnt/ß-catenin signaling pathway. Thus, this study provided novel insights into the cellular and molecular mechanisms of Cd2+ toxicity on the vertebrate central nervous system (CNS), which might be helpful in developing pharmacotherapies to mitigate the neurological disorders resulting from exposure to Cd2+ and many other environmental heavy metals.

Effect of External Surface Diffusion Barriers on Platinum/Beta-Catalyzed Isomerization of n-Pentane.

We have developed a generalizable strategy to quantify the effect of surface barriers on zeolite catalysis. Isomerization of n-pentane, catalyzed by Pt/Beta, is taken as a model reaction system. Firstly, the surface modification by chemical liquid deposition of SiO2 was carried out to control the surface barriers on zeolite Beta crystals. The deposition of SiO2 leads to a very slight change in the physical properties of Beta crystals, but an obvious reduction in Brønsted acid sites. Diffusion measurements by the zero-length column (ZLC) method show that the apparent diffusivity of n-pentane can be more than doubled after SiO2 deposition, indicating that the surface barriers have been weakened. Catalytic performance was tested in a fixed-bed reactor, showing that the apparent catalytic activity improved by 51-131 % after SiO2 deposition. These results provide direct proof that reducing surface barriers can be an effective route to improve zeolite catalyst performance deteriorated by transport limitations.

Cooperation of ESIPT and ICT Processes in the Designed 2-(2'-Hydroxyphenyl)benzothiazole Derivative: A Near-Infrared Two-Photon Fluorescent Probe with a Large Stokes Shift for the Detection of Cysteine and Its Application in Biological Environments.

A rationally designed near-infrared two-photon fluorescent probe (SDP-A) for selectively detecting cysteine (Cys) has been developed based on a newly designed conjugation-enhanced 2-(2'-hydroxyphenyl)benzothiazole derivative as the fluorophore, an acrylate moiety as the Cys reaction site, and an N-methylpyridinium scaffold as both the unit of organelle targeting and improving water solubility. The probe SDP-A alone essentially emitted no fluorescence, whereas it achieved a superb near-infrared fluorescence emission (713 nm) enhancement within 15 min with a significant Stokes shift (302 nm) in the presence of Cys. The photoluminescence mechanism of the probe SDP-A toward Cys was modulated by excited-state intramolecular proton transfer (ESIPT) and intramolecular charge transfer (ICT) processes. It exhibited high selectivity and sensitivity (LOD = 102 nM) for monitoring Cys over other analytes such as Hcy/GSH/H2S owing to a specific conjugate addition-cyclization reaction between Cys and the acrylate moiety. More importantly, the released fluorophore SDP exhibits elevated quantum yields (1.52-18.17%) in different solvents and strong two-photon excited fluorescence with a sizeable two-photon action cross-section (Φ) of 213.5 GM at 820 nm in acetonitrile-PBS medium, which is highly desirable for two-photon fluorescence imaging of the living samples. Therefore, SDP-A was successfully applied to the imaging of Cys in live cells, zebrafish, mouse brain, and abdominal cavity down to a depth of more than 200 µm using a one/two-photon fluorescence microscope.

Early monoclonal protein decline pattern is an independent prognostic factor in patients with multiple myeloma.

Patients always have different responses to the same treatment due to the heterogeneity of multiple myeloma (MM). However, the relationship between monoclonal protein (M-protein) reduction rates during treatment and survival prognosis in MM patients remains controversial. We retrospectively analyzed 198 newly diagnosed MM patients who received regular bortezomib-based chemotherapy for at least 2 cycles and subsequent autologous stem cell transplantation (ASCT) plus continuous maintenance. The relationship between the early M-protein reduction rates and survival prognosis was evaluated. This study is the first to divide patients into three patterns, namely, A, B, and C, according to the M-protein reduction rate during the first two therapy cycles. The results showed that pattern B patients with progressive reduction in M-protein had better progression-free survival (PFS) and overall survival (OS) than did pattern A or C patients with precipitating or slow M-protein reduction (75.33 ± 18.81 versus 41.23 ± 9.13 or 26.60 ± 6.67 months; P < 0.001; 117.33 ± 18.44 versus 71.00 ± 10.06 or 39.73 ± 24.10 months; P = 0.003, respectively). In addition, biological analysis showed that pattern A + C patients had higher international staging system (ISS) stage III proportions (P = 0.008) and lactate dehydrogenase (LDH) elevations (P = 0.044) than pattern B patients. Furthermore, pattern A + C was a significant independent adverse parameter for PFS and OS (HR = 2.62, P = 0.001; HR = 2.15, P = 0.022, respectively). Thus, our results demonstrate that pattern A + C indicates an inferior survival prognosis in MM.

The effect of spleen tyrosine kinase inhibitor R406 on diabetic retinopathy in experimental diabetic rats.

PURPOSE: To investigate the effect of spleen tyrosine kinase (Syk) inhibitor R406 on diabetic retinopathy (DR) in diabetic mellitus (DM) rats. METHODS: Rats were randomized into Normal, DM, DM + 5 mg/kg R406 and DM + 10 mg/kg R406 groups. DM rats were established via injection of streptozotocin (STZ). One week after model establishment, rats in treatment groups received 5 mg/kg or 10 mg/kg R406 by gavage administration for 12 weeks consecutively, followed by the detection with hematoxylin-eosin (HE) staining, Evans blue angiography, retinal trypsin digestion assay, Western blotting, immunohistochemistry, TUNEL assay, immunofluorescence assay and quantitative reverse transcriptase real-time polymerase chain reaction (qRT-PCR). RESULTS: The retina of DM rats presented different degree of edema, disordered and loose structure, swollen cells with enlarged intercellular space, and dilated and congested capillaries. Besides, the retinal vessels of DM rats showed high fluorescence leakage. However, R406 alleviated the above-mentioned conditions, which was much better with high concentration of R406 (10 mg/kg). R406 also reversed the down-regulations of occludin, claudin-5, ZO-1 and the up-regulation of and VEGF in retinal tissues of DM rats; inhibited retinal cell apoptosis; strengthened retinal cell proliferation; and reduced expressions of IL-1ß, IL-6, TNF-α and nuclear p65 NF-κB in retinal tissues. The improvement in all these indexes was much more significant in rats of DM + 10 mg/kg R406 group than in rats of DM + 5 mg/kg R406 group. CONCLUSION: Syk inhibitor R406 could attenuate retinal inflammation in DR rats via the repression of NF-κB activation.

Fasudil protects retinal ganglion cells and promotes axonal regeneration.

This study was aimed to investigate whether fasudil can protect retinal ganglion cells and promote axonal regeneration by inhibiting RhoA/Rock pathway. Long Evans rats were used to establish an optic nerve injury model. Apoptosis was detected by TUNEL, and surviving RGCs was detected by Fluoro-Gold retrograde label and hematoxylin-eosin (HE) staining was used to evaluate pathological changes and western blot was used to measure the expression of protein. After 10 days of optic nerve injury rat model, increased cell apoptosis and decreased FG-positive RGCs in rat eye, but fasudil could reverse these changes. In vitro, fasudil could not only increase the number of RGCs with protuberances, but also increase the length of protuberances. Moreover, fasudil could not only reduce the expression of total-cohoin, Rock, total-cofilin and total-MLC protein induced by optic nerve injury, but also reduce the relative expression of GTP-RhoA, p-cofilin and p-MLC protein. Fasudil protects retinal ganglion cells and promotes axonal regeneration by inhibiting RhoA / Rock pathway.

1q21 Gain Combined with High-Risk Factors Is a Heterogeneous Prognostic Factor in Newly Diagnosed Multiple Myeloma: A Multicenter Study in China.

BACKGROUND: The prognostic value of 1q21 gain in newly diagnosed multiple myeloma (NDMM) remains controversial. Our aim was to investigate the prognostic value of 1q21 gain in a Chinese population. MATERIALS AND METHODS: We retrospectively identified 565 patients with NDMM from multiple centers in China. RESULTS: We detected 1q21 gain in 222 (39.3%) patients, among whom 144 had three copies of 1q21, 57 had four copies of 1q21, and 21 had at least five copies of 1q21. Copy number variation did not show any effect on the disease outcome. Multivariate analysis indicated that 1q21 gain was an independent factor for poor prognosis, but we found that 1q21 gain was strongly associated with other high-risk factors, such as del(17p), t(4;14), t(14;16), lactate dehydrogenase (LDH) level >300 U/L and International Scoring System (ISS) stage II-III (p < .001). Further analysis revealed that in the absence of other high-risk factors, isolated 1q21 gain resulted in similar progression-free survival (PFS; 52.0 vs. 52.8 months, p = .810) and overall survival (OS; not reached vs. not reached, p = .833); additionally, when present with other high-risk cytogenetic abnormalities or increased LDH levels, 1q21 gain lost its prognostic power. However, the presence of 1q21 gain increased the adverse impact of ISS stage. Furthermore, 1q21 gain predicted poor PFS and OS in patients who received bortezomib-based regimens. Moreover, autologous stem cell transplantation reversed the poor prognosis in patients with 1q21 gain. CONCLUSION: Our results show that heterogeneity exists among patients with 1q21 gain and suggest that we should assess the impact of 1q21 gain on prognosis according to different treatment regimens and accompanying high-risk factors. IMPLICATIONS FOR PRACTICE: 1q21 gain is one of the most common chromosomal aberrations in multiple myeloma (MM); however, the prognostic value of 1q21 gain remains controversial. This study investigated the prognostic value of 1q21 gain in a Chinese population with newly diagnosed MM. The results showed that heterogeneity exists among patients with 1q21 gain and suggested that the impact of 1q21 gain on prognosis should be assessed according to different treatment regimens and accompanying high-risk factors. These results could help stratify risk in patients with MM and guide treatment decisions.

Microbial antigens-loaded myeloma cells enhance Th2 cell proliferation and myeloma clonogenicity via Th2-myeloma cell interaction.

BACKGROUND: Myeloma cells retain B cell functions, considered to be potential antigen presenting cells, yet there is little information regarding promoting Th2 cell proliferation or the direct effects to myeloma on the Th2 cells stimulated by microbial antigens-loaded myeloma cells. METHODS: Mixed lymphocyte reaction was used colorimetric assays via CCK8-kit. Surface molecular expression was performed by flow cytometry, cells sorting using microbeads. The concentrations of cytokines in serum were assessed using an ELISA kit. Clonogenic assay were performed in a methylcellulose culture system. Statistical analysis was assessed using the Student's t-test or one-way analysis of variance for multiple comparisons test. RESULTS: The expression of HLA-DR, CD80 and CD40 on RPMI8266 cell membrane surface was upregulated by interaction with interferon-γ and/or Bacillus Calmette-Guerin Vaccine (BCGV). RPMI8266 cells were able to induce the mixed lymphocyte reaction in a dose-dependent fashion. The Th2 ratio induced by RPMI8266 treated by BCGV and interferon-γ (treated-RPMI8266) cells was only slightly greater than by untreated-tumor cells, but the serum IL-4 level secreted by Th2 cells was markedly higher in treated-RPMI8266 cells group. Th2 cells stimulated by treated-myeloma cells could directly promote treated-myeloma cell clonogenicity in a dose-dependent manner. Anti-HLADR IgG2b completely blocked increased of IL-4 secretion by Th2 cells stimulated by treated-myeloma cells, while also blocked enhancing the clonogenicity of treated tumor cells stimulated by MM-Th2 cells. CONCLUSIONS: These results indicate that a novel mechanism of myeloma pathogenesis in myeloma cells could act as an APC to present microbial Ags to Th2 cells, promoting Th2 cell proliferation, consequently facilitating tumor development by close interaction between Th2 myeloma cells. Taken together, the microbial Ag presenting course of MM-Th2-MM interactions-restricted by MHC class-II-may result in tumor development such that all factors involved in the system could have a potential for myeloma therapeutic intervention.

Serum ferritin, an early marker of cardiovascular risk: a study in Chinese men of first-degree relatives with family history of type 2 diabetes.

BACKGROUND: Ferritin is one of the key proteins that regulate iron homeostasis and is widely available clinical biomarker of iron status. This study aimed to discuss the influence of serum ferritin (SF) on cardiovascular risk factors in the first-degree relatives with family history of type 2 diabetes (FHD). METHODS: This cross-sectional study included 232 men. Anthropometric measurements and blood samples were analyzed. The people were divided into four groups according to median SF (102.8 ng/ml) and people with or without FHD. Group A (FHD-and low SF), group B (FHD-and high SF), group C (FHD+ and low SF), and group D (FHD+ and high SF). RESULTS: The subjects in different categories of SF concentrations showed significant differences in BMI (SF main effect: P = 0.010), WC (P = 0.030), SBP (P < 0.001), FPG (P < 0.001), PPG-2 h (P < 0.001), FINS (P < 0.001), and HOMA-IR (P = 0.015; all: 2-way ANOVA). There was a significant difference in SBP (FHD main effect: P = 0.003), DBP (P = 0.006), and FINS (P = 0.013, all: 2-way ANOVA) between the groups with or without FHD. The interaction term between SF and FHD was significant for SBP (P = 0.011), DBP (P = 0.012), and PPG-2 h (P = 0.022). Logistic analysis showed that accumulation of CVD risk factors, which were ≥ 2 items and ≥ 3 items in group D were 7.546 and 3.343 times higher compared with group A (P < 0.05). CONCLUSIONS: The increased SF levels increased the risk of cardiovascular risk factors and the occurrence of insulin resistance in first-degree relatives with FHD.

Fecal Microbiota Taxonomic Shifts in Chinese Multiple Myeloma Patients Analyzed by Quantitative Polimerase Chain Reaction (QPCR) and 16S rRNA High-Throughput Sequencing.

BACKGROUND Increasing evidence has suggested that gut flora play an important role in tumor progression and prognosis. However, the relationship between fecal microbiota and hematologic malignancy requires further investigation. This study aimed to characterize the relationship of the fecal microbial community in multiple myeloma (MM) patients. MATERIAL AND METHODS A total of 40 MM patients and healthy controls (n=17) were retrospectively collected from the First Affiliated Hospital of Sun Yat-sen University between October 2018 and May 2019. The fecal samples were collected for 16S rRNA high-throughput sequencing for the fecal microbial community, as well as diversity and correlation analysis. Furthermore, 21 MM patients and their family members were selected for the matched pair analysis to confirm the fecal microbiota taxonomic changes by qRT-PCR assay. RESULTS Diversity analysis showed that diversity measured by Shannon index was lower in MM patients compared with healthy controls. At the phylum level, higher abundances of Proteobacteria but lower abundances of Actinobacteria were identified in the MM group in comparison with the healthy control group. At the genus level, the proportion of Bacteroides, Faecalibacterium, and Roseburia was significantly higher in the MM group. The matched pair analysis showed that Pseudomonas aeruginosa and Faecalibacterium were significantly more abundant in the MM group. Further analysis on prognostic risk factors revealed that the Faecalibacterium prausnitzii level was significantly correlated with ISS stage. CONCLUSIONS Our study highlights the imbalanced composition and diversity of the gastrointestinal microbiome in MM patients, which could be further used as a potential biomarker for MM risk screening, therapeutic strategies, and prognostic prediction.