Objective To investigate the efficacy of imatinib combining with allogeneic hematopioetic stem cell transplantation or chemotherapy for bcr-abl positive acute lymphoblastic leukemia (ALL). Methods 12 cases were diagnosed on morphology, cytochemistry, immunophenotype and bcr-abl fusion gene. The induction is imatinib (400 mg/d) combining chemotherapy. 8 cases accepted allogeneic hematopoietic stem cell transplantation after complete remission (CR). If bcr-abl became positive, the patient was treated with imatinib (400～600 mg/d). 3 cases were tested with imatinib alternating chemotherapy after cr. Results 11 patients gained CR, CR rate 91.7 %; 5 patients (41.7 %) became bcr-abl negative through 2 courses induction. 3 cases relapsed after transplantation. 2 cases relapsed in imatinib combining chemotherapy group. The median remission interval is 16 months (imatinib combining transplantation group) and 10 months (imatinib combining chemotherapy group) (P <0.01) respectively. The median survival time is 18 months (imatinib combining transplantation group), and the other group (imatinib combining chemotherapy) is 12 months (P <0.01). Conclusion Imatinib combining chemotherapy achieved high CR rate for the bcr-abl positive ALL. Imatinib combining allogeneic hematopoietic stem cell transplantation is superior to imatinib combining chemotherapy for CR patients.

Objective To prepare celastrol ethosomes and to observe the permeability characteristics of the ethosomes which act as the transdermal delivery carriers of celastrol in vitro. Methods Celastrol ethosomes were prepared by ethanol injection method, and then the encapsulation efficiency, particle size, polydispersity index ( PDI) and zeta potential of the ethosomes were analyzed. TP2A intelligent percutaneous penetration instrument was used to compare the skin penetration properties of celastrol ethosomes, celastrol solution and the mixture of blank ethosomes with celastrol solution. Results The prepared celastrol ethosomes were spherical, and the average particle size was (401.3 ± 5.5) nm, PDI was 0.21± 0.02, steady zeta potential was (-2.75 ± 0.1) mV, and average encapsulation efficiency was ( 80.6 ± 0.7) %. The amount of accumulative penetration of celastrol ethosomes at 48 h was 76.86 μg·cm -2 and the permeation rate was 1.640 9 μg·cm -2·h -1, which were significantly higher than the celastrol solution and the mixture of blank ethosomes with celastrol solution. Conclusion The prepared ethosomes have high encapsulation efficiency, uniform particle size and stable quality, and are beneficial to the transdermal absorption of celastrol.

Photoaffinity labeling is widely applied to demonstrate targets of small molecule ligands. In this paper, biotin photoaffinity labeled molecule with propargyl group 1 has been designed and synthesized, followed it's labeling of N2-acetyl-2'-O-propargyl guanosine 9 by "click chemistry". This technology presents delight development potential in labeling of second messenger cyclic nucleotide, antisense oligonucleotide or siRNA.
Biotin ; chemistry ; Click Chemistry ; Guanosine ; chemical synthesis ; chemistry ; Ligands ; Photoaffinity Labels

This article dealed with the effects of processing method and duration on the major bioactive components (sinigrin and sinapine thiocyanate) in Brassica juncea. The contents of sinigrin and sinapine thiocyanate in decoctions of raw and processed B. juncea were determined and compared by high performance liquid chromatography on a Alltima C18 column (4.6 mm x 250 mm, 5 microm) at 35 degrees C with the acetonitrile-0.1% phosphoric acid as the mobile phrase in gradient elution. The detection wavelength of sinigrin and sinapine thiocyanate was set at 227 nm and 326 nm, and the flow rate was 1.0 mL x min(-1). It was found that with the extended processing duration, the contents of sinigrin and sinapine thiocyanate first increased and then decreased: i.e., 0-2 minutes they increased gradually (for sinigrin, by 9.65% in processed products and 356. 10% in powder; for sinapine thiocyanate, by 12.82% in processed products and 3.41% in powder), and achieved their highest content at 2 min; then, decreased during the next 5 minutes (for sinigrin, by 80.35% in processed products and 82.09% in powder; for sinapine thiocyanate, by 14.29% in processed products and 17.54% in powder), suggesting that processing duration could significantly affect the contents of bioactive components in B. juncea, enzymatic hydrolysis of sinigrin when the seed is crushed in the present of moisture may be responsible for the content change. It is recommended that the slow fire should be the best processing method and the raw seed could be used directly in the water extracts related industrial production.
Brassica ; chemistry ; Choline ; analogs & derivatives ; chemistry ; Drugs, Chinese Herbal ; chemistry ; Glucosinolates ; chemistry ; Powders ; chemistry ; Thiocyanates ; chemistry

AIM AND METHODSTo study the roles of carbon monoxide on hypoxic pulmonary vasoconstriction (HPV) by investigating the effects of exogenous carbon monoxide and heme oxygenase inhibitor ZnPPIX on hypoxic vasoconstriction reaction of isolated rat pulmonary arterial rings (PAR).

RESULTSHypoxia caused constriction in PAR preconstricted by PE. Both ZnPPIX and carbon monoxide inhibited hypoxic pulmonary constriction significantly by increasing the cGMP level after hypoxia.

CONCLUSIONZnPPIX and exogenous carbon monoxide can inhibit HPV. The reduction of cGMP induced by the decreased of CO may be one of reasons of HPV.

Animals ; Carbon Monoxide ; physiology ; Hypoxia ; In Vitro Techniques ; Male ; Pulmonary Artery ; physiology ; Rats ; Rats, Wistar ; Vasoconstriction ; physiology

OBJECTIVE:To observe the clinical efficacy and safety of Buzhong yiqi wuling decoction combined with western medicine in the treatment of chronic congestive heart failure(CHF). METHODS:120 CHF patients were divided into observation group and control group by random number table method,with 60 cases in each group. Control group received conventional western medicine treatment as rest,low salt diet and diuretics. Observation group was additionally given Buzhong yiqi wuling decoction,one dose a day,at twice,on the basis of control group. Treatment course of 2 groups lasted for 2 weeks. Average TCM symptom score, level of plasma NT-proBNP,6 min walk test(6MWT)distance before and after treatment,clinical efficacy and the occurrence of ADR were compared between 2 groups. RESULTS:Before treatment,there was no statistical significance in average TCM symptom score,level of plasma NT-proBNP and 6MWT distance between 2 groups(P>0.05). After treatment,average TCM symptom score and level of plasma NT-proBNP of 2 groups were decreased significantly,and the observation group was more significant than the control group,with statistical significance(P<0.05);6MWT distance of 2 groups were improved significantly compared to before treatment,and the observation group was significantly longer than the control group,with statistical significance(P<0.05). After treatment,total effective rate of observation group(93.33%)was significantly higher than that of control group(83.33%),with sta-tistical significance(P<0.05). No obvious ADR was found in 2 groups. CONCLUSIONS:Buzhong yiqi wuling decoction is an ef-fective prescription to treat CHF,and can relieve clinical symptoms,improve the cardiac function,decrease NT-proBNP level and en-hance the patient exercise tolerance with good safety.

Pathological cardiac hypertrophy is a maladaptive response in a variety of organic heart disease(OHD),which is characterized by mitochondrial dysfunction that results from disturbed energy metabolism. SIRT3, a mitochondria-localized sirtuin, regulates global mitochondrial lysine acetylation and preserves mitochondrial function. However, the mechanisms by which SIRT3 regulates cardiac hypertrophy remains to be further elucidated. In this study, we firstly demonstrated that expression of SIRT3 was decreased in AngiotensionⅡ(AngⅡ)-treated cardiomyocytes and in hearts of AngⅡ-induced cardiac hypertrophic mice. In addition, SIRT3 overexpression protected myocytes from hypertrophy, whereas SIRT3 silencing exacerbated Ang II-induced cardiomyocyte hypertrophy.In particular,SIRT3-KO mice exhibited significant cardiac hypertrophy. Mechanistically, we identified NMNAT3 (nicotinamide mononucleotide adenylyltransferase 3), the rate-limiting enzyme for mitochondrial NAD biosynthesis, as a new target and binding partner of SIRT3.Specifically,SIRT3 physically interacts with and deacety-lates NMNAT3,thereby enhancing the enzyme activity of NMNAT3 and contributing to SIRT3-mediated anti-hypertrophic effects.Moreover,NMNAT3 regulates the activity of SIRT3 via synthesis of mitochon-dria NAD.Taken together,these findings provide mechanistic insights into the negative regulatory role of SIRT3 in cardiac hypertrophy.Sirtuin 3(SIRT3),a mitochondrial deacetylase that may play an impor-tant role in regulating cardiac function and a potential target for CHF

OBJECTIVETo study the impact of the chloride channel dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) on the cytoskeleton of Sertoli cells in the mouse.

METHODSTM4 Sertoli cells were cultured and treated with CFTR(inh)-172 at the concentrations of 1, 5, 10 and 20 μmol/L for 48 hours. Then the cytotoxicity of CFT(inh)-172 was assessed by CCK-8 assay, the expressions of F-actin and Ac-tub in the TM4 Sertoli cells detected by immunofluorescence assay, and those of N-cadherin, vimentin and vinculin determined by qPCR.

RESULTSCFTR(inh)-172 produced cytotoxicity to the TM4 Sertoli cells at the concentration of 20 μmol/L. The expressions of F-actin and Ac-tub were decreased gradually in the TM4 Sertoli cells with the prolonging of treatment time and increasing concentration of CFTR(inh)-172 (P < 0.05). The results of qPCR showed that different concentrations of CFTR(inh)-172 worked no significant influence on the mRNA expressions of N-cadherin, vimentin and vinculin in the Sertoli cells.

CONCLUSIONThe CFTR chloride channel plays an important role in maintaining the normal cytoskeleton of Sertoli cells. The reduced function and expression of the CFTR chloride channel may affect the function of Sertoli cells and consequently spermatogenesis of the testis.

Actins ; metabolism ; Animals ; Benzoates ; pharmacology ; Chloride Channels ; physiology ; Cystic Fibrosis Transmembrane Conductance Regulator ; antagonists & inhibitors ; Cytoskeleton ; drug effects ; Male ; Mice ; Sertoli Cells ; drug effects ; metabolism ; Spermatogenesis ; Thiazolidines ; pharmacology ; Time Factors

Objective To investigate the safety and feasibility of operation to treat left renal carcinoma with Mayo Ⅱ tumor thrombus in double inferior vena cava.Methods The clinical data from a 52-year-old male suffered painless gross hematuria for 6 days and left back pain for 3 days was analyzed retrospectively.Enhanced CT examination of kidneys showed double inferior vena cava malformation.The confluence level of the left and the right inferior vena cava was at L1/2 disc level by a 80 degree angle.The left inferior pole of kidney showed an irregular soft tissue density,the size was 6.1 cm × 4.5 cm × 5.6 cm,considering the possibility of renal cancer.The tumor thrombus invaded into the inferior vena cava below the hepatic vein with a maximum diameter of about 3.2 cm.The top of the tumor thrombus was about 6.0 cm above the left renal vein.It showed a Mayo Ⅱ] tumor thrombus.Preoperative diagnosis was left renal carcinoma with Mayo Ⅱ tumor thrombus in double inferior vena cava.The patient underwent radical nephrectomy under general anesthesia.We separated hepatic inferior vena cava,right renal vein,right inferior vena cava,left inferior vena cava and left renal vein.Sequential occlusion was completed of left inferior vena cava,right inferior vena cava,right renal vein,hepatic inferior vena cava.Vascular wall of inferior vena cava was cut open and the tumor thrombus was removed at the level of inferior vena cava bifurcation.During the operation,the wall of left inferior vena cava was invaded by tumor thrombus.So all the left kidney,the left renal vein,the left inferior vena cava invaded by tumor thrombus were resected.We sutured the vena cava incision continuously.Sequential occlusions were removed of right renal vein,right inferior vena cava,hepatic inferior vena cava.We clamped the vessel wall of right inferior vena cava by auricle clamp and made an incision longitudinally.Then we made an end to side anastomosis of the left and right inferior vena cava.Results The surgical procedure was successful and the postoperative recovery was favorable.The operation time was 442 min.And blood loss was 3 000 ml.The postoperative pathology result showed that the tumor was clear cell renal cell carcinoma,2016 WHO/ISUP grade was Ⅱ] to Ⅲ.There was no metastasis of left renal hilum lymph node,abdominal aorta and vena cava lymph node.There was no metastasis of adrenal gland.The abdominal cavity drainage tube and the urinary catheter was removed 7 days postoperatively.He was discharged from hospital 8 days postoperatively.There were no obvious postoperative complications.The patient was followed up for 3 months and there was no tumor recurrence or metastasis.Conclusions Our initial clinical result show that radical nephrectomy,Mayo]Ⅱ venous thrombectomy,left and right inferior vena cava end to side anastomosis is safe and effective.But the operation is difficult and complex.

Objective To investigate the effect of resveratrol on the proliferation, migration and angiogenic ability of HUVECs mediated by Rictor over-expression adenovirus.Methods The Rictor was obtained through PCR and cloned into GV314 plasmid to construct recombinant plasmid, then co-transfected 293T cells with helper plasmids to obtain Rictor overexpressing adenoviral particles(Ad-Rictor),the vector without target gene Ad-Null was set as the negative control group.Ad-Rictor and Ad-Null were infected HUVECs respectively,we also set up blank control group and resveratrol-intervention group(Ad-Rictor+Res). The expression of recombinant protein was detected by fluorescence microscopy and Western blot. CCK-8 assay,wound healing and matrigel assay were performed to as-sess the proliferation,migration and tube formation of HUVECs. Results We constructed Ad-Rictor and Ad-Null which may infect HUVECs and express Rictor protein efficiently. Ad-Rictor could significantly improve the prolifer-ation,migration and lumen formation (P<0.05), resveratrol intervention may significantly inhibit these functions induced by Ad-Rictor (P<0.05). Conclusions Resveratrol inhibits the proliferation, migration and angiopoietic ability of HUVECs through targeting mTORC2/Rictor.