YOLOv7-RepFPN: Improving real-time performance of laparoscopic tool detection on embedded systems.

This study focuses on enhancing the inference speed of laparoscopic tool detection on embedded devices. Laparoscopy, a minimally invasive surgery technique, markedly reduces patient recovery times and postoperative complications. Real-time laparoscopic tool detection helps assisting laparoscopy by providing information for surgical navigation, and its implementation on embedded devices is gaining interest due to the portability, network independence and scalability of the devices. However, embedded devices often face computation resource limitations, potentially hindering inference speed. To mitigate this concern, the work introduces a two-fold modification to the YOLOv7 model: the feature channels and integrate RepBlock is halved, yielding the YOLOv7-RepFPN model. This configuration leads to a significant reduction in computational complexity. Additionally, the focal EIoU (efficient intersection of union) loss function is employed for bounding box regression. Experimental results on an embedded device demonstrate that for frame-by-frame laparoscopic tool detection, the proposed YOLOv7-RepFPN achieved an mAP of 88.2% (with IoU set to 0.5) on a custom dataset based on EndoVis17, and an inference speed of 62.9 FPS. Contrasting with the original YOLOv7, which garnered an 89.3% mAP and 41.8 FPS under identical conditions, the methodology enhances the speed by 21.1 FPS while maintaining detection accuracy. This emphasizes the effectiveness of the work.

Aponermin or placebo in combination with thalidomide and dexamethasone in the treatment of relapsed or refractory multiple myeloma (CPT-MM301): a randomised, double-blinded, placebo-controlled, phase 3 trial.

BACKGROUND: Aponermin, a circularly permuted tumor necrosis factor-related apoptosis-inducing ligand, is a potential death receptor 4/5-targeted antitumour candidate. Previous phase 1/2 studies have demonstrated the efficacy of aponermin in patients with relapsed or refractory multiple myeloma (RRMM). To confirm the superiority of aponermin plus thalidomide and dexamethasone (aponermin group) over placebo plus thalidomide and dexamethasone (placebo group) in RRMM, a randomized, double-blinded, placebo controlled phase 3 trial was performed. METHODS: Four hundred seventeen patients with RRMM who had previously received at least two regimens were randomly assigned (2:1) to receive aponermin, thalidomide, and dexamethasone or placebo, thalidomide, and dexamethasone. The primary endpoint was progression-free survival (PFS). Key secondary endpoints included overall survival (OS) and overall response rate (ORR). RESULTS: A total of 415 patients received at least one dose of trial treatment (276 vs. 139). The median PFS was 5.5 months in the aponermin group and 3.1 months in the placebo group (hazard ratio, 0.62; 95% confidence interval [CI], 0.49-0.78; P < 0.001). The median OS was 22.4 months for the aponermin group and 16.4 months for the placebo group (hazard ratio, 0.70; 95% CI, 0.55-0.89; P = 0.003). Significantly higher rates of ORR (30.4% vs. 13.7%, P < 0.001) and very good partial response or better (14.1% vs. 2.2%, P < 0.0001) were achieved in the aponermin group than in the placebo group. Treatment with aponermin caused hepatotoxicity in some patients, as indicated by the elevated alanine transaminase, aspartate transaminase, or lactate dehydrogenase levels (52.2% vs. 24.5%, 51.1% vs. 19.4% and 44.9% vs. 21.6%, respectively), mostly grade 1/2, transient and reversible. The main grade 3/4 adverse events included neutropenia, pneumonia and hyperglycemia. The incidence of serious adverse events was similar between the two groups (40.6% vs. 37.4%). There was no evidence that aponermin leads to hematological toxicity, nephrotoxicity, cardiotoxicity, or secondary tumors. CONCLUSIONS: Aponermin plus thalidomide and dexamethasone significantly improved PFS, OS and ORR with manageable side effects in RRMM patients who had received at least two prior therapies. These results support the use of aponermin, thalidomide, and dexamethasone as a treatment option for RRMM patients. TRIAL REGISTRATION: The trial was registered at http://www.chictr.org.cn as ChiCTR-IPR-15006024, 17/11/2014.

Regulatory Effect and Mechanism of Erythroblastic Island Macrophages on Anemia in Patients with Newly Diagnosed Multiple Myeloma.

Objective: To examine the clinical characteristics and anemia-related factors in patients with newly diagnosed multiple myeloma (NDMM), as well as the effect and mechanism of erythroblastic islands (EBIs) and EBI macrophages in NDMM patients with anemia. Methods: We collected and analyzed clinical data to find anemia-related factors. Using flow cytometry, the numbers and ratios of erythroblasts and EBI macrophages were determined. RNA sequencing (RNA-seq) was used to determine the differences of EBI macrophages in NDMM patients with or without anemia. Results: Based on the clinical characteristics of NDMM patients with anemia, MCV, abnormal levels of albumin, osteolytic lesions, and Durie-Salmon (DS) stage are risk factors for anemia. Patients with anemia have fewer erythroblasts, erythroblastic islands (EBIs), and EBI macrophages in their bone marrow than patients without anemia. RNA-seq analysis of EBI macrophages from the bone marrow of patients with and without anemia revealed that macrophages from patients with anemia are impaired and tend to promote the production of interleukin-6, which has been demonstrated to be an essential survival factor of myeloma cells and protects them from apoptosis. Conclusion: In NDMM patients with anemia, EBI macrophages are impaired, which causes anemia in those patients. Our finding highlights the significance of EBI macrophages in anemia in NDMM patients and provides a new strategy for recovery from anemia in these patients.

Low-dose decitabine plus bortezomib-dexamethasone therapy is well-tolerated and highly effective on first-relapsed multiple myeloma: a single-center phase 2 trial.

An open-label, single-center, phase 2 trial of a second-line therapy comprising low-dose decitabine (DAC) plus bortezomib (Bort) and dexamethasone (DXM) (Dvd) in relapsed and/or refractory multiple myeloma (RRMM) patients was conducted to screen available and inexpensive agents, aiming to work synergistically with other existing anti-melanoma drugs at reasonable prices, and effectively treat Bort and/or Len-refractory patients. Forty-seven patients were included according to the inclusion criteria, with only 1 withdrawal due to premature death. After 17.2 (range: 0.5-24.1) months of median follow-up, all the 46 cases had halted or completed DVd therapy per protocol, with an overall response rate (ORR) of 87.0%. Meanwhile, DVd was indicated to induce high, deep, and lasting responses, dependent of prior treatment or baseline characteristics. The results revealed that DVd is well-tolerated and highly effective in the treatment of first-relapsed RRMM (including those with Bort-refractory disease) patients.

[Percutaneous foraminal endoscopy for the treatment of lumbar lateral recess stenosis in elderly].

OBJECTIVE: To investigate the clinical efficacy and safety of percutaneous foraminal endoscopy in the treatment of lumbar lateral recess stenosis in elderly. METHODS: The clinical data of 31 elderly patients with lumbar lateral recess stenosis treated by percutaneous foraminal endoscopic decompression from March 2018 to August 2019 were retrospectively analyzed. Including 16 males and 15 females, aged from 65 to 81 years with an average of (71.13±5.20) years, the course of disease ranged from 3 months to 7 years with an average of (14.36±6.52) months. Visual analogue scale (VAS) and Oswestry disability index (ODI) were used to assess clinical symptom and functional status before operation and 1, 6, 12 months after operation. At the final follow-up, the modified Macnab standard was used to evaluate clinical efficacy. RESULTS: All patients were completed the operation successfully. The operation time was from 75 to 120 min with an average of (97.84±11.22 ) min. All 31 patients were followed up from 12 to 28 months with an average of (17.29±5.56) months. Postoperative lumbago-leg pain VAS and ODI were significantly improved at 1, 6, and 12 months(P<0.01). At the final follow-up, according to the modified Macnab standard to evaluate the effect, 23 got excellent results, 5 good, 3 fair. One patient had severe adhesions between peripheral tissues and nerve root, and postoperative sensory abnormalities in the lower extremities were treated conservatively with traditional Chinese medicine and neurotrophic drugs, which recovered at 2 weeks after surgery. No complications such as nerve root injury and infection occurred. CONCLUSION: The intervertebral foraminal endoscopy technique, which is performed under local anesthesia for a short period of operation, ensures adequate decompression while minimizing complications, and is a safe and effective surgical procedure for elderly patients with lumbar lateral recess stenosis.

Influence Factors of Multifunctional Viscous Drag Reducers and Their Optimization for Unconventional Oil and Gas Reservoirs.

Owing to the problems of guar gum fracturing fluid and conventional slickwater fracturing fluid systems in hydraulic fracturing of tight oil reservoirs, such as bad fracture network capacity, high damage, and low sand-carrying performance, researchers are actively looking for new alternative fracturing fluids. This study takes four commonly used additives for hydraulic fracturing of tight oil and gas reservoirs in western China, including the conventional polyacrylamide friction reducer EM30S, bioglue, thickener CHS-1, and high-viscosity friction reducer HVFR-1. By testing the water solubility, rheological properties, drag reduction, sand-carrying performance, imbibition oil displacement effect, and residue content of the four additives, the best additives suitable for hydraulic fracturing of tight oil and gas reservoirs were selected, and a set of indoor evaluations and the experimental method of screening hydraulic fracturing additives for tight oil and gas reservoirs were established. The research results show that the high-viscosity slickwater system composed of CND + HVFR-1 is more suitable for hydraulic fracturing of tight oil and gas reservoirs. Compared with the other three types of additives, CND + HVFR-1 fracturing fluid has good water solubility, and the dissolution time is less than 30 s. Therefore, in order to save construction time, the CND + HVFR-1 high-viscosity slickwater system is first recommended for field application. The research results of rheological properties show that although the apparent viscosity of high-concentration HVFR-1 + CND is low, the cross value of G' and G″ is the smallest (0.006 Hz) and the elastic modulus is the largest (4.554 Pa) corresponding to 1 Hz. HVFR-1 + CND has better sand-carrying performance when used as a sand-carrying liquid. CND + HVFR-1 not only achieves a friction reduction rate of more than 60% but also has the effect of imbibition oil displacement to improve oil recovery; it can easily break gels, and its low residue content can ensure rapid flowback after construction is completed, and the lower residue content also causes the least damage to the reservoir. At the same time, the establishment of this evaluation method provides a certain reference for other researchers who select fracturing fluids for tight oil and gas reservoirs.

miR-17-3p promotes the proliferation of multiple myeloma cells by downregulating P21 expression through LMLN inhibition.

Multiple myeloma (MM), a hematological malignancy, has a poor prognosis and requires an invasive procedure. Reports have implicated miRNAs in the diagnosis, treatment and prognosis of hematological malignancies. In our study, we evaluated the expression profiles of miR-17-3p in plasma and bone marrow mononuclear cells of monoclonal gammopathy of undetermined significance (MGUS) and MM patients and healthy subjects. The results showed that the plasma and mononuclear cell expression levels of miR-17-3p in MM patients were higher than those in MGUS patients and normal controls. In addition, the expression of miR-17-3p was positively correlated with diagnostic indexes, such as marrow plasma cell abundance and serum M protein level, and positively correlated with the International Staging System stage of the disease. Receiver operating characteristic curve analysis suggested that miR-17-3p might be a diagnostic index of MM. Moreover, miR-17-3p regulated cell proliferation, apoptosis and the cell cycle through P21 in MM cell lines and promoted MM tumor growth in vivo. Furthermore, we predicted and verified LMLN as a functional downstream target gene of miR-17-3p. Negatively regulated by miR-17-3p, LMLN inhibits MM cell growth, exerting a tumor suppressive function through P21. Taken together, our data identify miR-17-3p as a promising diagnostic biomarker for MM in the clinic and unveil a new miR-17-3p-LMLN-P21 axis in MM progression.

Glutathione combined with mecobalamin in the treatment of chemotherapy-induced peripheral neuropathy in multiple myeloma: a retrospective clinical study.

BACKGROUND: This study sought to examine the use of glutathione combined with mecobalamin in the prevention and treatment peripheral neuropathy (PN) in multiple myeloma (MM) patients, observe its effectiveness and safety, and explore the risk factors and prognostic factors of chemotherapy-induced peripheral neuropathy (CIPN). METHODS: Patients in the study group were administered 2.4 g of glutathione intravenously once daily 2-3 days before chemotherapy, combined with 500 µg of mecobalamin administered intravenously once every other day until the end of the chemotherapy cycle. Patients who did not use this regimen were selected as a control group. Differences in adverse reactions, treatment efficiency, progression-free survival (PFS), and overall survival (OS) between the two groups were retrospectively analyzed. PFS and OS curves were plotted using the Kaplan-Meier method. The univariate analysis rates were compared using the χ2 test. The multivariate analysis was performed by a logistic regression analysis. The proportional hazard regression model was used for the univariate and multivariate proportional hazards model analyses. RESULTS: The incidence of PN, especially grade 2 and 3 PN, was more decreased in the study group than the control group. The history of diabetes (P=0.032) and the method of bortezomib injection (P=0.043) was found to affect the PN grade. The multivariate logistic regression analysis showed that diabetes was an independent risk factor of PN in MM patients [odds ratio (OR) =3.484, P=0.020]. The Proportional hazards model multivariate analysis showed that extramedullary disease (EMD) [hazard ratio (HR) =2.373, P=0.006] and elevated lactic dehydrogenase (LDH) (HR =1.934, P=0.009) were independent prognostic factors for MM patients. CONCLUSIONS: Glutathione combined with mecobalamin significantly reduced the incidence and severity of CIPN in MM patients, and did not increase the adverse reactions of patients with MM. Diabetes and bortezomib intravenously increased the incidence and severity of PN in patients with MM.

Analysis of the efficacy and safety of bortezomib for treating newly diagnosed multiple myeloma through different administration methods.

BACKGROUND: This study aims to compare the efficacy and adverse reactions of bortezomib for treating newly diagnosed multiple myeloma (MM) through two different administration methods: intravenous (IV) injection and subcutaneous (SC) injection. METHODS: A retrospective analysis was performed in 205 patients with newly diagnosed MM, who were treated by the Department of Hematopathology, Henan Cancer Hospital, from June 2009 to December 2017. These patients were divided into two groups according to the treatment methods: IV injection group, IV injection of bortezomib; SC injection group, SC injection of bortezomib. RESULTS: After the first course of treatment, the effect of very good partial remission (VGPR) or above (≥VGPR) in the IV injection group (IV group) and SC injection group (SC group) was 31.0% and 14.3%, respectively (P=0.004), while the overall response rate (ORR) was 72.0% and 49.5%, respectively (P=0.001). From the 2nd course to the 6th course of treatment, the ORR was not statistically different between these two groups. No significant difference was found in median progression-free survival (37 vs 45 months) and overall survival (63 vs 59 months). A lower frequency of adverse events, especially Grade 3 peripheral neuropathy, was observed in SC group compared with the IV group. CONCLUSION: Compared with IV administration, SC bortezomib can provide a better balance between efficacy and toxicity.

The Biological Function and Clinical Significance of miR-886-5p in Multiple Myeloma.

BACKGROUND: miR-886-5p plays an important role in many tumors, but it has been rarely investigated in multiple myeloma (MM). We studied the expression of miR-886-5p in the plasma of MM patients and in MM cell lines, and evaluated its biological function to identify its potential involvement in MM. METHODS: We recruited 16 subjects including 10 newly diagnosed MM patients who had not received treatment and 6 healthy individuals. The expression of miR-886-5p in plasma and MM cell lines was examined by quantitative reverse transcription polymerase chain reaction. Cell Counting Kit-8, colony formation assay, and 7-amino-actinomycin D/allophycocyanin double staining were performed to detect the function of miR-886-5p in MM cell lines. The expression of Bax and p53 was determined by western blot. RESULTS: The expression of miR-886-5p in the plasma of MM patients was higher than that in normal individuals and its level in MM cell lines was higher than that in peripheral blood mononuclear cells isolated from healthy individuals. miR-886-5p could trigger the cell proliferation and inhibition of apoptosis and affect the cell cycle. CONCLUSION: miR-886-5p triggered MM cell growth and may act as a diagnostic plasma biomarker for MM, potentially contributing to resistance to chemotherapy.

Retrospective analysis of the efficacy and influencing factors of autologous hematopoietic stem cell transplantation for multiple myeloma.

This study aims to review the clinical efficacy and factors affecting the treatment of multiple myeloma (MM) by autologous hematopoietic stem cell transplantation (ASCT). The clinical data of 47 patients with MM from the Department of Hematology of Henan Cancer Hospital from September 2010 to July 2018 were retrospectively analyzed. At pre-transplantation of autologous cells, 25.5% were in complete remission (CR), 14.9% were in very good partial remission (VGPR) and 59.6% were in partial remission (PR). Among these cases, one case had PR after three recurrences. At post-transplantation, 51% were in CR, including two cases who received double transplantations, 27.7% were in VGPR, and 21.3% were in PR. The median follow-up time was 27.6 months (4-96 months). The 3-year progression free survival (PFS) and overall survival (OS) were 47.9% and 79.6%, respectively. The Analysis of variance (ANOVA) results revealed that factors that affected OS were international staging system (ISS) stage (P = 0.002), CR and VGPR post-transplantation (P = 0.002), while factors that affected PFS were ISS stage (P = 0.005), pre-transplant induction therapy (P = 0.032), and disease risk stratification (P = 0.017). The curative effects for PFS were CR and VGPR pre-transplantation (P = 0.013) and post-transplantation (P = 0.011). The Cox multivariate regression analysis revealed that ISS stage and CR and VGPR post-transplantation were independent prognostic factors of OS. At post-transplantation, CR and VGPR, ISS stage, and pre-transplant induction therapy were independent prognostic factors for PFS. In conclusion, ASCT can improve the clinical efficacy and survival rate of MM patients. ISS stage, CR and VGPR post-transplantation are independent prognostic factors of OS and PFS, while pre-transplant induction therapy is an independent prognostic factor for PFS.

[Treatment of L4,5 lumbar disc herniation with percutaneous endoscopic lumbar discectomy through two different approaches].

OBJECTIVE: To analyze the clinical efficacy, indications and operative points of transforaminal approach and interlaminar approach in the treatment of L4,5 lumbar disc herniation. METHODS: A retrospective analysis was performed on 48 patients with L4,5 lumbar disc herniation treated by percutaneous endoscopic lumbar discectomy from November 2016 to June 2018. Among them, 32 patients underwent percutaneous endoscopic transforaminal discectomy(PETD), including 17 males and 15 females, with an average age of (60.22±16.55) years, and the course of disease was(2.18±2.68) months;16 patients underwent percutaneous endoscopic interlaminar discectomy(PEID), including 7 males and 9 females, with an average age of (42.25±15.89) years, and the course of disease was(2.90±3.02) months. VAS, ODI of two groups before operation, 3 days, 3 months, and 6 months after operation were analyzed, and modified Macnab standard was used to evaluate the clinical effects. RESULTS: All the 48 patients successfully completed the surgical treatment, and all patients were followed up. There was no significant difference in gender, course of disease and follow-up time between two groups (P>0.05). The age of PETD group was(60.22±16.55) years and PEID group was (42.25±15.89) years, there was statistical difference between two groups (P<0.05 ). In the PETD group, there were 10 patients with advanced age, non-free type(24 cases) was more than free type(8 cases), and shoulder type(27 cases) more than axillary type(1 case) and ventral type(4 cases). PETD was used in 5 patients with lateral type and 2 patients with extreme lateral type. In PEID group, the axillary type(8 cases) was more than the shoulder type(2 cases) and the ventral type(6 cases), PEID was used in 4 patients with high prolapse free type(I and IIregions). VAS scores and ODI of patients in two groups at each postoperative follow-up point were significantly improved compared with those before surgery(P<0.05). According to modified Macnab standard to evaluate the clinical effect, in PETD group, 24 cases obtained excellent results, 5 good, 2 fair, 1 poor, while in PEID group, 12 excellent, 3 good, 0 fair, 1 poor. CONCLUSIONS: Both two surgical approachs can achieve satisfactory efficacy in treating L4,5 lumbar disc herniation, but PETD is more suitable for elderly patients, non-free type, lateral type, extremely lateral type and shoulder type of lumbar disc herniation. High prolapse(I and II regions) and axillary type lumbar prominent should select PEID.

Clinical observation of recombinant human endostatin in treating relapsed refractory multiple myeloma.

Recombinant human endostatin (rhES) can inhibit multiple myeloma, while its clinical efficacy in treating relapsed refractory multiple myeloma (RRMM) has not been assessed. One hundred and eleven RRMM patients were treated with four different regimens: combination of VD (velcade+dexamethasone) and rhES (n = 25), Thalidomide (Tha) and VD (VTD, n = 22) combination, rhES and conventional chemotherapy combination (n = 32), and combination of conventional chemotherapy and Tha (n = 32). Significant differences were found in progression-free survival (PFS) between rhES combination groups and conventional chemotherapy combination groups. No statistical difference was found in overall response rate, overall survival or incidences of adverse effects. The combination of rhES with VD or conventional chemotherapy is active in patients with RRMM and prolongs the PFS to improve the quality of life.

[Application of broad easy immediate surgery in percutaneous transforaminal endoscopic technology for lumbar lateral recess stenosis in the elderly].

OBJECTIVE: To explore the safety and effectiveness of percutaneous transforaminal endoscopic BEIS technology for lumbar lateral recess stenosis in the elderly. METHODS: From February 2014 to May 2016, 21 patients with lumbar lateral recess stenosis in elderly were treated with percutaneous endoscopic BEIS. There were 13 males and 8 females, aged from 70 to 85 years old with an average of 74.3 years. Preoperative, 1 and 12 months postoperative visual analogue scale(VAS) scores and Oswestry Disability Index(ODI) were statistically analyzed. MacNab was used to assess the clinical effects. RESULTS: All the operations were successful. The time ranged from 90 to 130 min with an average of 110 min. All the patients were followed up for 12 to 38 months with an average of 18 months. Preoperative, 1 and 12 months postoperative VAS scores were 8.47±1.23, 1.78±0.72, 0.68±0.32, and ODI scores were 32.48±10.03, 19.53±3.55, and 5.15±1.02, respectively. Postoperative scores of VAS and ODI were obviously improved(P<0.05). According to modified MacNab standard to evaluate the clinical effects, 14 cases obtained excellent results, 5 good, 2 fair. Lower limb paresthesia occurred in 1 case, and the condition was restored at 3 months postoperatively with conservative treatment. One patient was complicated with emphysema before operation secondary to pulmonary infection, and was effectively controlled with regulate antibiotic therapy. No infection of vertebral body or intervertebral space, no injuries of blood vessels or nerve root, no tear of dura, or the leakage of cerebrospinal fluid were found. CONCLUSIONS: Percutaneous transforaminal endoscopic BEIS is a safe and effective method for lumbar lateral recess stenosis in the elderly.

Discovery of Distinctin-Like-Peptide-PH (DLP-PH) From the Skin Secretion of Phyllomedusa hypochondrialis, a Prototype of a Novel Family of Antimicrobial Peptide.

Amphibian skin secretions are an important treasure house of bioactive antimicrobial peptides (AMPs). Despite having been the focus of decades of research in this context, investigations of phyllomedusine frogs continue to identify new AMPs from their skin secretions. In this study, the prototype of a novel family of AMP distinctin-like-peptide-PH (DLP-PH) was identified from the skin secretion of the otherwise well-studied Tiger-Legged Tree Frog Phyllomedusa hypochondrialis through cloning of its precursor-encoding cDNA from a skin secretion-derived cDNA library by a 3'-rapid amplification of cDNA ends (RACE) strategy. Subsequently, the mature peptide was isolated and characterized using reverse-phase HPLC and MS/MS fragmentation sequencing. DLP-PH adopted an α-helical conformation in membrane mimetic solution and demonstrated unique structural features with two distinct domains that differed markedly in their physiochemical properties. Chemically synthesized replicates of DLP-PH showed antimicrobial activity against planktonic bacterial and yeast cells, but more potent against Escherichia coli at 32 µg/mL. However, DLP-PH showed much weaker inhibitory activity against the growth of sessile cells in biofilms. In addition, DLP-PH exhibited anti-proliferative activity against human cancer cell lines, H157, and PC3, but with no major toxicity against normal human cell, HMEC-1. These combined properties make DLP-PH deserving further study as an antimicrobial agent and further investigations of its structure-activity relationship could provide valuable new insights into drug lead candidates for antimicrobial and/or anti-cancer purposes.

Comparative Analysis of miRNA Expression Profiles of Multiple Myeloma with 1q21 Gains and Normal FISH.

BACKGROUND: Multiple myeloma (MM) with 1q21 gains invariably has a poor prognosis. Many recent studies have reported the relationship between micro (mi)RNA expression and MM prognosis. However, there is little information on the association between miRNA alterations and 1q21 gains. METHODS: We compared the miRNA expression profiles of MM with 1q21 gains and MM with normal fluorescence in situ hybridisation (FISH) by gene expression array. Differentially expressed miRNAs were identified using Affymetrix TAC software. Thresholds were defined as a false discovery rate <0.05, p value <0.05, and n-fold change >2. RESULTS: Six miRNAs (let-7f-5p and -7g-5p, and miR-29a-3p, -29b-1-5p, -331-3p, and -223-3p) were downregulated and 4 (miR-30e-5p, -17-3p, -18b-5p, and -19a-3p) were upregulated in MM with 1q21 gains relative to MM with normal FISH. CONCLUSIONS: The identified set of miRNAs can serve as biomarkers for distinguishing MM with 1q21 gains from MM with normal FISH.

Rosmarinic acid counteracts activation of hepatic stellate cells via inhibiting the ROS-dependent MMP-2 activity: Involvement of Nrf2 antioxidant system.

Recently, oxidative stress is involved in hepatofibrogenesis. Matrix metalloproteinase-2 (MMP-2) is required for activation of hepatic stellate cells (HSCs) in response to reactive oxygen species (ROS). This study was designed to explore the hypothesis that the inhibitory effect of rosmarinic acid (RA) on HSCs activation might mainly result from its antioxidant capability by increasing the synthesis of glutathione (GSH) involved in nuclear factor kappa B (NF-κB)-dependent inhibition of MMP-2 activity. Here, we demonstrate that RA reverses activated HSCs to quiescent cells. Concomitantly, RA inhibits MMP-2 activity. RNA interference-imposed knockdown of NF-κB abolished down-regulation of MMP-2 by RA. RA-mediated inactivation of NF-κB could be blocked by the diphenyleneiodonium chloride (DPI; a ROS inhibitor). Conversely, transfection of dominant-negative (DN) mutant of extracellular signal-regulated kinases 2 (ERK2), c-Jun N-terminal kinase 1 (JNK1), or p38α kinase had no such effect. Simultaneously, RA suppresses ROS generation and lipid peroxidation (LPO) whereas increases cellular GSH in HSC-T6 cells. Furthermore, RA significantly increased antioxidant response element (ARE)-mediated luciferase activity, nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and catalytic subunits from glutamate cysteine ligase (GCLc) expression, but not modulatory subunits from GCL (GCLm). RA-mediated up-regulation of GClc is inhibited by the shRNA-induced Nrf2 knockdown. The knocking down of Nrf2 or buthionine sulfoximine (a GCL inhibitor) abolished RA-mediated inhibition of ROS. Collectively, these results provide novel insights into the mechanisms of RA as an antifibrogenic candidate in the prevention and treatment of liver fibrosis.

Treatment of refractory/relapsed adult acute lymphoblastic leukemia with bortezomib-based chemotherapy.

Nine pretreated patients aged >19 years with relapsed/refractory acute lymphoblastic leukemia (ALL) were treated with a combination of bortezomib plus chemotherapy before allogeneic hematopoietic stem cell transplantation (allo-HSCT). Eight (88.9%) patients, including two Philadelphia chromosome-positive ALL patients, achieved a complete remission. Furthermore, the evaluable patients have benefited from allo-HSCT after response to this reinduction treatment. We conclude that bortezomib-based chemotherapy was highly effective for adults with refractory/relapsed ALL before allo-HSCT. Therefore, this regimen deserves a larger series within prospective trials to confirm these results.