[The effect of peripheral blood cell score on the prognosis of multiple myeloma patients treated with bortezomib].

Objective: This study aims to evaluate the prognostic effect of peripheral blood cells in multiple myeloma (MM) patients treated with bortezomib. Methods: The clinical data of 155 newly diagnosed MM patients in two blood disease treatment centers from January 2014 to December 2016 were retrospectively studied. All patients received bortezomib as the first-line treatment. The results of the peripheral blood cell counts, including absolute neutrophil count, absolute monocyte count (AMC) , hemoglobin level, mean corpuscular volume (MCV) , and platelet count, and other clinical features were analyzed. Results: AMC (>0.6×10(9)/L) , MCV (>99.1 fl) , and platelet count (<150×10(9)/L) significantly affected patients' PFS and OS. The above three factors were assigned 1 point, respectively, to form the blood cell score. The analysis showed that 64 cases (41.3% ) had a score of 0, 57 cases (36.8% ) had 1, 32 cases (20.6% ) had 2, and 2 cases (1.3% ) had 3. The median PFS of the four groups were 42.8 m, 26.5 m, 15.8 m, and 6.4 m, respectively (P<0.001) . The median OS were NR, 48.2 m, 31.1 m, and 31.4 m, respectively (P=0.001) . Multivariate analysis suggested that the blood cell score (2-3 vs 0-1) and the proportion of marrow plasma cells (>30% ) were independent prognostic factors for PFS (HR=1.95 and 1.76, respectively) , while age (>65y vs ≤65y) , R-ISS stage (3 vs 1-2) , and blood cell score (2-3 vs 0-1) were independent prognostic factors for OS (HR=2.08, 2.13 and 2.12, respectively) . Conclusion: As an easy-to-access biomarker, the blood cell score can be used to evaluate the prognosis of newly diagnosed MM patients in the era of new drugs, but it is still necessary to expand the cases and make further confirmation in the prospective study.

MicroRNA-186 improves fracture healing through activating the bone morphogenetic protein signalling pathway by inhibiting SMAD6 in a mouse model of femoral fracture: An animal study.

OBJECTIVES: MicroRNAs (miRNAs) have been reported as key regulators of bone formation, signalling, and repair. Fracture healing is a proliferative physiological process where the body facilitates the repair of a bone fracture. The aim of our study was to explore the effects of microRNA-186 (miR-186) on fracture healing through the bone morphogenetic protein (BMP) signalling pathway by binding to Smad family member 6 (SMAD6) in a mouse model of femoral fracture. METHODS: Microarray analysis was adopted to identify the regulatory miR of SMAD6. 3D micro-CT was performed to assess the bone volume (BV), bone volume fraction (BVF, BV/TV), and bone mineral density (BMD), followed by a biomechanical test for maximum load, maximum radial degrees, elastic radial degrees, and rigidity of the femur. The positive expression of SMAD6 in fracture tissues was measured. Moreover, the miR-186 level, messenger RNA (mRNA) level, and protein levels of SMAD6, BMP-2, and BMP-7 were examined. RESULTS: MicroRNA-186 was predicted to regulate SMAD6. Furthermore, SMAD6 was verified as a target gene of miR-186. Overexpressed miR-186 and SMAD6 silencing resulted in increased callus formation, BMD and BV/TV, as well as maximum load, maximum radial degrees, elastic radial degrees, and rigidity of the femur. In addition, the mRNA and protein levels of SMAD6 were decreased, while BMP-2 and BMP-7 levels were elevated in response to upregulated miR-186 and SMAD6 silencing. CONCLUSION: In conclusion, the study indicated that miR-186 could activate the BMP signalling pathway to promote fracture healing by inhibiting SMAD6 in a mouse model of femoral fracture.Cite this article: Bone Joint Res 2019;8:550-562.

[Inflammatory myofibroblastic tumor of the larynx: a case report].

Inflammatory myofibroblastic tumor(IMT) is a kind of mesenchymal tumor. It commonly occurs in the lungs. It rarely occurs in head and neck. A 81 years old man presented to the otolaryngology clinic with hoarseness for 40 days. Electron laryngoscopy revealed a right vocal mass(10 mm×10 mm). Under MRI, the lesion in right vocal fold was shown as soft tissue mass with unclear border, and had a slightly hyperintense on T1 weighted images and slightly hyperintense on T2 weighted images.The histopathological result showed that fibrous connective tissue was infiltrated by various kinds of inflammatory cells including lymphocytes and plasma cells with marked atypia and mitoses, and angiogenesis was also found in the lesion. Immunochemistry showed that smooth muscle actin(SMA) (+), Ki 67(40%), S 100(-), Desmin(-), CD34(-),CK(-), and anaplastic lymphoma kinase protein(-). The histopathological result suggested that the lesion was inflammatory myofibroblastic tumor.

Bone marrow mesenchymal stem cells overexpressing human basic fibroblast growth factor increase vasculogenesis in ischemic rats

Administration or expression of growth factors, as well as implantation of autologous bone marrow cells, promote in vivo angiogenesis. This study investigated the angiogenic potential of combining both approaches through the allogenic transplantation of bone marrow-derived mesenchymal stem cells (MSCs) expressing human basic fibroblast growth factor (hbFGF). After establishing a hind limb ischemia model in Sprague Dawley rats, the animals were randomly divided into four treatment groups: MSCs expressing green fluorescent protein (GFP-MSC), MSCs expressing hbFGF (hbFGF-MSC), MSC controls, and phosphate-buffered saline (PBS) controls. After 2 weeks, MSC survival and differentiation, hbFGF and vascular endothelial growth factor (VEGF) expression, and microvessel density of ischemic muscles were determined. Stable hbFGF expression was observed in the hbFGF-MSC group after 2 weeks. More hbFGF-MSCs than GFP-MSCs survived and differentiated into vascular endothelial cells (P<0.001); however, their differentiation rates were similar. Moreover, allogenic transplantation of hbFGF-MSCs increased VEGF expression (P=0.008) and microvessel density (P<0.001). Transplantation of hbFGF-expressing MSCs promoted angiogenesis in an in vivo hind limb ischemia model by increasing the survival of transplanted cells that subsequently differentiated into vascular endothelial cells. This study showed the therapeutic potential of combining cell-based therapy with gene therapy to treat ischemic disease.

Bone marrow mesenchymal stem cells overexpressing human basic fibroblast growth factor increase vasculogenesis in ischemic rats.

Administration or expression of growth factors, as well as implantation of autologous bone marrow cells, promote in vivo angiogenesis. This study investigated the angiogenic potential of combining both approaches through the allogenic transplantation of bone marrow-derived mesenchymal stem cells (MSCs) expressing human basic fibroblast growth factor (hbFGF). After establishing a hind limb ischemia model in Sprague Dawley rats, the animals were randomly divided into four treatment groups: MSCs expressing green fluorescent protein (GFP-MSC), MSCs expressing hbFGF (hbFGF-MSC), MSC controls, and phosphate-buffered saline (PBS) controls. After 2 weeks, MSC survival and differentiation, hbFGF and vascular endothelial growth factor (VEGF) expression, and microvessel density of ischemic muscles were determined. Stable hbFGF expression was observed in the hbFGF-MSC group after 2 weeks. More hbFGF-MSCs than GFP-MSCs survived and differentiated into vascular endothelial cells (P<0.001); however, their differentiation rates were similar. Moreover, allogenic transplantation of hbFGF-MSCs increased VEGF expression (P=0.008) and microvessel density (P<0.001). Transplantation of hbFGF-expressing MSCs promoted angiogenesis in an in vivo hind limb ischemia model by increasing the survival of transplanted cells that subsequently differentiated into vascular endothelial cells. This study showed the therapeutic potential of combining cell-based therapy with gene therapy to treat ischemic disease.

Lung recruitment maneuver during proportional assist ventilation of preterm infants with acute respiratory distress syndrome.

OBJECTIVE: To investigate the effect of lung recruitment maneuver (LRM) with positive end-expiratory pressure (PEEP) on oxygenation and outcomes in preterm infants ventilated by proportional assist ventilation (PAV) for respiratory distress syndrome (RDS). STUDY DESIGN: Preterm infants on PAV for RDS after surfactant randomly received an LRM (group A, n=12) or did not (group B, n=12). LRM entailed increments of 0.2 cm H2O PEEP every 5 min, until fraction of inspired oxygen (FiO2)=0.25. Then PEEP was reduced and the lung volume was set on the deflation limb of the pressure/volume curve. When saturation of peripheral oxygen fell and FiO2 rose, we reincremented PEEP until SpO2 became stable. RESULT: Group A and B infants were similar: gestational age 29.5 ± 1.0 vs 29.4 ± 0.9 weeks; body weight 1314 ± 96 vs 1296 ± 88 g; Silverman Anderson score for babies at start of ventilation 8.6 ± 0.8 vs 8.2 ± 0.7; initial FiO2 0.56 ± 0.16 vs 0.51 ± 0.14, respectively. The less doses of surfactant administered in group A than that in group B (P<0.05). Groups A and B showed different max PEEP during the first 12 h of life (8.4 ± 0.5 vs 6.7 ± 0.6 cm H2O, P=0.00), time to lowest FiO2 (101 ± 18 versus 342 ± 128 min; P=0.000) and O2 dependency (7.83 ± 2.04 vs 9.92 ± 2.78 days; P=0.04). FiO2 levels progressively decreased (F=43.240, P=0.000) and a/AO2 ratio gradually increased (F=30.594, P=0.000). No adverse events and no differences in the outcomes were observed. CONCLUSION: LRM led to the earlier lowest FiO2 of the first 12 h of life and a shorter O2 dependency.