Animals ; Antiparasitic Agents ; therapeutic use ; Bronchopneumonia ; drug therapy ; parasitology ; Child ; China ; Combined Modality Therapy ; Diagnosis, Differential ; Humans ; Male ; Myiasis ; complications ; diagnosis ; parasitology ; therapy ; Skin Diseases, Parasitic ; drug therapy ; parasitology ; surgery ; Treatment Outcome

Objective To compare the efficacy and toxicity of thalidomide-COMP (T-COMP) and thalidomide-VAD (T-VAD) regimens in previously untreated multiple myeloma (MM) patients.Methods Forty-nine newly diagnosed MM patients were randomly allocated to either A group (thalidomide-MP/-COMP,19 cases) or B group (thalidomide-VAD,30 cases).All patients received thalidomide 200 mg p.o.daily.Patients in group A received additionally vincristine 0.4 mg i.v.on day 1-4,cyclophosphamide 200 mg i.v.on day 1-4,melphalan 4 mg tid p.o.on days 1-5,prednisone 60 mg p.o.daily on days 1-5.Patients in group B received additionally vincristine 0.4 mg i.v.on day 1-4 and epirubicin 10 mg/m2 i.v.,on day 1-4 and dexamethasone 40 mg p.o.daily on days 1-4,9-12 and 17-20 for the first cycle and on days 1-4 for the next three cycles.Treatment was administered every 28 days.The therapeutic response was evaluated based on the International Myeloma Working Group Criteria (IMWG 2006) after the treatment.The toxicity was graded according to NCI common terminology criteria for adverse events v 3.0.Results On an intention-to-treat basis,at least partial therapeutic response was observed.The rates were 73.7 ％ and 53.3 ％ in group A and B respectively (x2 =2.029,P =0.154).Overall survival (OS) rate at 2 years were 52.6 ％ (10/19) in group A and 53.3 ％ (16/30) in group B,respectively (x2 =2.468,P =0.116).Considering overall toxicity,constipation,peripheral neuropathy,dizziness/somnolence,skin rash and edema were significantly higher in group B compared with group A,but the incidence of toxicities grade 3-4 was low and similar in both arms.Conclusion The overall response rate of T-MP/T-COMP regimen is similar with that of T-VAD regimen,suggesting this regimen cannot be chosen as the first treatment for patients with non-implantation therapy.

Objective To assess the efficacy of high dose dexamethasone combined with bortezomib and thalidomide in multiple myeloma (MM) patients with acute renal failure.Methods 23 newly diagoosed MM patients with acute renal failure were treated with high dose dexamethasone combined with bortezomib and thalidomide.Results Reversal of renal failure was documented in 58.3 ％ (7/12) of those severe renal failure patients and 81.8 ％ (9/11) of renal failure patients.Renal function was reversed in 69.5 ％ (16/23) of all patients.The total response rate for MM was 60.9 ％ (14/23).The median time to response was 2 (1-5) months. Overall survival (OS) at 3 years was 56.5 ％ and the median survival time was 34.4 months.Conclusion Renal failure was reversible in the majority of newly diagnosed MM patients treated with highdose dexamethasone containing regimens.The addition of novel agents thalidomide and (or) bortezomib is safe and induces a more rapid renal failure reversal compared with routine chemotherapy.

Objective: To investigate the mechanism responsible for homoharringtonine (HHT), which contributes to imatinib (IM) sensitivity in the chronic myeloid leukemia (CML) cell line. Methods:We established cell lines from a patient with CML at the time of first diagnosis and relapse phase, and designated the cell lines as NPHA1 and NPHA2, respectively. Stable underexpressed EphB4 cells (NPHA2-EphB4-sh) were obtained. Leukemia cell lines were incubated with HHT. The activated signal proteins in cells were tested by Western blot. Results:EphB4 was overexpressed in IM-resistant NPHA2 compared with the NPHA1 cell line. However, the expression of EphB4 mRNA and protein were significantly decreased in knockdown NPHA2-EphB4-sh cells compared with the NPHA2 and NPHA1 (P<0.001) cell lines. NPHA2-EphB4-sh cells were sensitive to IM (IC50:0.93 mg/L), and NPHA2 showed IM re-sistance (IC50 : 5.45 mg/L) (P<0.001). However, co-stimulation with HHT+IM decreased IC50 of NPHA2 cells to 1.17 mg/L (P<0.001). Meanwhile, phospho-Rac1/cdc42 was significantly increased in NPHA2 cells compared with NPHA2-EphB4-sh (P<0.001). HHT blocked the expression of EphB4/RhoA. Conclusion: The overexpression of EphB4 contributed to IM resistance in CML line cells. EphB4/RhoA may be a new marker of IM resistance. HHT with IM yielded more treatment advantages than IM alone by blocking EphB4/RhoA pathways.

BackgroundGlaucoma is an optic neuropathy caused by structural damage of the optic nerve,and its early diagnosis is critical for arresting the irreversible damage of visual function. Optical coherence tomography (OCT) allows an early diagnosis of glaucoma by the measurements of the optic disc and retinal nerve fiber parameters. Objective This study was carried out to evaluate the effects of optic disc tomography and the measurement of the retinal nerve fiber layer (RNFL)thickness by spectral-domain OCT on the diagnosis of glaucomatous eye. MethodsIt was a noninterventional, cross-sectionalstudy. The optic disctopographic parameters and total and regional RNFL thickness were measured by RTVue OCT in 62 normal eyes and 67 glaucomatous eyes. The area under the receiver operating characteristic curve( ROC ) was used to assess the ability to differentiate glaucoma eyes from normal eyes of each testing parameter. This trial complied with the Helsinki Declaration and was approved by the Clinical Trial Ethic Committee of Beijing TongrenHospital. All of the participants signed the written informed consent before any medical examination. Results In the comparison of demography ,the ages of patients, the mean deficiency( MD ) and pattern standard difference( PSD ) of perimetry were obviously larger in the glaucoma group, primary open angle glaucoma ( POAG ) group and primary closure-angle glaucoma(PACG) group than those of normal controls( P＜0. 01 ). No significant differences were found in the disc area between a total glaucoma group, POAG group or PACG group and normal group ( P =0. 101,0. 741 and 0. 652, respectively) ;however, the average RNFL thickness between normal eyes and glaucomatous eyes were significantly different( 109. 758 μm versus 79. 539 μm, P＜0. 01 ). Among the eight regions around the optic disc, the thickest RNFL located at the inferotemporal( 150. 109 μm) and superotemporal( 146. 105 μm) regions in normal eyes,and at the superotemporal( 104. 354 μm) and inferotemporal( 102. 436 μm) regions in glaucomatous eyes. Both in normal and glaucomatous eyes,the thinnest RNFL located at the nasal(NU+NL) and temporal(TU + TL) regions. For optic disc topographic parameters,the highest ROC were observed in rim volume( ROC--0. 850,0. 841 and 0. 862 in total glaucoma,POAG and PACG, respectively) and vertical cup/disc ratio( ROC =0. 840,0. 849 and 0. 830 in total glaucoma,POAG and PACG,respectively), and the sensitivities for specificity cutoff set at 80％ were 73.1％ and 76. 1％ in total glaucoma,73.0％ and 81.1％ in POAG and 73.3％ and 70.0％ in PACG, respectively. For RNFL thickness ,the highest ROC was observed in average RNFL( ROC =0. 925,0. 910 and 0. 942 in total glaucoma, POAG and PACG,respectively) ,and the sensitivities for specificity cutoff set at 80％ were 89. 6％ ,89.2％ and 90. 0％ in total glaucoma,POAG and PACG, respectively. Among the eight regions around the optic disc, RNFL thickness of region IT achieved the highest ROC, RNFL thickness of region TU and TL had the lowest ROC. Conclusions RTVue OCT appears to be of fair discriminating ability in distinguishing normal from glaucomatous eyes. RTVue OCT shows promise for the diagnosis of glaucoma.

This study was aimed to investigate the effect of D-limonene on K562 leukemia cells and its mechanism. Inhibitory effect of D-limonene on proliferation of K562 leukemia cells was assayed by MTT method and cell apoptosis was detected by flow cytometry and DNA agarose gel electrophoresis, the morphologic change of K562 cells was observed by microscopy. The results showed that when K562 cells were treated with 0.125 - 1.0 mmol/L of D-limonene for 48 hours, the proliferation of K562 cells was obviously inhibited in dose-dependent manner. Typical morphological changes and the typical DNA ladder on agarose gel electrophoresis for analysis of cellular apoptosis were significantly appeared in D-limonene treated K562 cells. Simultaneously, the sub-G1 peak was found in FCM analysis. It is concluded that the D-limonene can inhibit proliferation of K562 cells in dose-dependent manner, cause cell detained at G1 phase and induce apoptosis of K562 cells.
Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Cyclohexenes ; pharmacology ; Dose-Response Relationship, Drug ; Humans ; K562 Cells ; Terpenes ; pharmacology

BACKGROUND: Because of complicated physiological environment and difficulty to control experimental conditions, it is difficult to get satisfactory results from in vivo studies of cell mechanics.OBJECTIVE: To study the action and mechanism of p38MAPK signaling pathways on myoblast apoptosis based on successful construction of in vitro mechanical stimulation models.METHODS: The C2C12 cells cultured in vitro were divided into control group and SB203580 treatment group. Cyclic tensile stress was applied on the C2C12 myoblast cells for 0, 6, 12 and 24 hours in each group. The Flexcell Strain Unit-5000T was used to expose C2C12 myoblast cell to an equiaxial cyclic of 15% magnitude and a frequency of 10 cycles/min, each cycle including the 3 s stretch and 3 s relaxation. Hoechst 33258 fluorescent staining and optical microscope were used to detect cell apoptosis. RT-PCR, flow cytometric analysis were used to observe the apoptosis of C2C12 myoblast cells and Western blotting were used to detect the activity of p38MAPK and p-p38MAPK. RESULTS AND CONCLUSION: The optical microscope tested the change in the morphology. Hoechst 33258 staining showed that after treatment with cyclic stress, the cell took the typical appearance of apoptosis with chromatin condensation and apoptotic bodies. RT-PCR and flow cytometry showed that with the extension of time the rate of the apoptosis of C2C12 myoblast cell increased. And cells imposed SB203580 before imposing cyclical tensile stress, the results showed that the apoptosis was markedly affected, and the p-p38MAPK expression declined apparently. These findings demonstrate that p38MAPK signaling pathways in stress mediated into C2C12 myoblast cell apoptosis plays an important role.

Abstract The harm of head injury in skateboarding is more serious. The common injury cause is fall, collision, high speed impact. The primary types of injury include skull fracture, subdural hemorrhage, brain laceration contusion and concussion. Older children and adolescents, males, longboard, inappropriate sports venue are important risk factors for severe traumatic brain injury. Designing special skateboard parks and wearing protective equipment (helmets) can effectively reduce the incidence and severity of head injuries. The occurrence of injury can be reduced by adopting both legislation and education measures.

In order to evaluate the effect and mechanism of the mulberry leaf alkaloid, flavones, and polysaccharide intervention on diabetes, the overall metabolite profiling characteristics for the plasma of diabetic mouse was performed by using an ultra-performance liquid chromatography/electrospray-tandem mass spectrometry (UPLC-ESI-MS). The 8 potential biomarkers were found in diabetic mice plasma based on the data of MS/MS characteristics obtained from the UPLC-OrbitrapMS analysis, which mainly involved in sphingolipids, amino acid metabolic pathway. The principal component analysis showed that the normal group and model group were obviously distinguished and implied that metabolic disturbance was happened in diabetic mice plasma. The extracts of mulberry leaf flavonoids, polysaccharide, alkaloid had exhibited the effects of callback function for diabetic mice through regulating the amino acid metabolism and sphingolipid metabolism.
Alkaloids ; chemistry ; Amino Acids ; metabolism ; Animals ; Biomarkers ; blood ; Chromatography, High Pressure Liquid ; Diabetes Mellitus, Experimental ; drug therapy ; Flavones ; chemistry ; Flavonoids ; chemistry ; Metabolic Networks and Pathways ; Metabolomics ; Mice ; Morus ; chemistry ; Plant Leaves ; chemistry ; Sphingolipids ; metabolism ; Tandem Mass Spectrometry

OBJECTIVETo explore the possibility of repairing chemically induced acute hepatic injuries with allogeneic bone marrow stem cell (BMSC) transplantation.

METHODSA SD rat model of CCl(4)-induced acute hepatic injury was established, which received transplantation of BMSCs (2.0 ml, 1x10(6)/ml) or normal saline injection into the local liver parenchyma, respectively. The rats were sacrificed at 6 h before and 6 h, 1, and 5 weeks after transplantation, and the livers were prepared for microscopic examination.

RESULTSCellular necrosis, bridging necrosis, congestion in the hepatic sinusoid, and inflammatory cell infiltration were seen in the chemically injured livers 6 h after model establishment, and these changes were ameliorated in rats receiving BMSC transplantation.

CONCLUSIONSAllogeneic BMSC transplantation can repair chemically induced acute liver injuries.

Animals ; Bone Marrow Cells ; cytology ; Carbon Tetrachloride ; toxicity ; Chemical and Drug Induced Liver Injury ; etiology ; pathology ; surgery ; Hematopoietic Stem Cell Transplantation ; methods ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Treatment Outcome