Objective To investigate the molecular mechanism of action of isoglycoside-4'-O-apigenin(1 → 2)glucoside(licraside)intervention in alleviating cholestasis.Methods Farnesol X receptor(FXR)was silenced in human HepG2 cells using lentivirus,and bilirubin and α-isothiocyanate(ANIT)were used to induce HepG2 cells to construct a hypercholate-hyperbilirubin model.The effects of licraside on cell viability,biochemical indices contents and the expression level of FXR and its downstream related proteins in the model were investigated.HepG2 cells and FXR-silenced HepG2 cells were divided into normal,model and experimental groups.Bilirubin and probenecid were added to all groups except the normal group,and 80 μmol·L-1 licraside was added to the experimental group.After 24 h of culture,cell viability and the levels of total bile acids(TBA),bilirubin and other biochemical indices were examined in each group;the protein expression levels of FXR and bile salt efflux pump(BSEP)were examined in each group by Western blot assay.Results The cell viability in HepG2 cells normal group,HepG2 cells model group,HepG2 cells experimental group,siFXR-HepG2 cells normal group,siFXR-HepG2 cells model group and siFXR-HepG2 cells experimental group were(100.00±17.15)％,(39.41±2.91)％,(70.79±3.74)％,(81.41±5.12)％,(33.49±2.69)％and(44.08±4.82)％;the levels of TBA were(7.98±5.87),(46.18±10.93),(9.25±7.20),(11.18±3.36),(38.28±5.12)and(34.79±5.39)μmol·L-1;the levels of total bilirubin were(5.21±3.27),(40.29±24.88),(5.21±2.64),(12.00±4.64),(56.36±14.85)and(15.39±5.56)μmol·L-1;the relative expression levels of FXR protein were 1.00±0.10,0.81±0.07,1.11±0.09,0.10±0.02,0.12±0.02 and 0.10±0.04;the relative expression levels of BSEP protein were 1.00±0.17,0.81±0.02,0.88±0.03,0.70±0.09,0.49±0.07 and 0.60±0.10.The differences of the above indexes in the HepG2 cells experimental group compared with the model group were statistically significant(P＜0.001,P＜0.01);except for TBA,the differences of the above indexes in siFXR-HepG2 cells experimental group compared with the model group were statistically significant(P＜0.001,P＜0.01).Conclusion Licraside can effectively reduce the biochemical indices level of hypercholate-hyperbilirubin cell model.This effect is achieved by agonizing of FXR protein expression,increase the efflux of bile acid salt and then reduce the synthesis of bile acids,and eventually achieve the effect of alleviating the cholestasis.

OBJECTIVETo identify the side effect of all-trans retinoic acid (ATRA), and improve early therapeutic response in patients with acute promyelocytic leukemia (APL).

METHODThe first case of Sweet's syndrome (SS) developed in a APL patient treated with ATRA was reported in mainland of China, and reviewed correlative literature.

RESULTSOnly 14 cases of SS associated with ATRA therapy in APL have been reported in the literature, including the present case. The median age was 49.5 years (9 -84) and 10 were women and 4 men. Of them, SS was restricted to the skin in 10 case, the other 4 muscle, fascia, kidney, and lung were involved. SS appeared after a median of 18 days of ATRA therapy (6 - 34 days). The median WBC count was 7.05 (0.80 - 23.00) x 10(9)/L. Four patients continued with the ATRA therapy without interruption, 13 patients treated with steroids and 12 responded. One patient improved without any treatment. Two cases of SS developed retinoic acid syndromes after ATRA therapy.

CONCLUSIONSweet's syndrome is a rare adverse effect of ATRA, and has similar features with inflammatory or infective dermatosis. The corticosteroids treatment could improve the systemic and cutaneous symptoms. When ATRA therapy was restarted after SS subsided, no recurrence of rashes was observed.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Female ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; Male ; Middle Aged ; Sweet Syndrome ; chemically induced ; Tretinoin ; adverse effects ; therapeutic use

Adolescent ; Adult ; Aged ; Female ; Hepatitis B, Chronic ; pathology ; physiopathology ; Humans ; Liver ; pathology ; Liver Cirrhosis ; pathology ; Male ; Middle Aged ; Receptor, Cannabinoid, CB1 ; analysis ; Young Adult

OBJECTIVETo prepare and identify a polyclonal antibody (pAb) against (mouse) cysteinyl leukotriene receptor 1 (CysLT(1)) and to investigate the changes of CysLT(1) receptor expression in BV2 microglial cells after rotenone treatment.

METHODSRabbits were immunized with KLH-coupled CysLT(1) peptide to prepare the pAb. The titer of the pAb in rabbit plasma was detected by ELISA method, and the specificity of the pAb was tested by antigen blockade. After BV2 cells were treated with rotenone (0.01-1 μmol/L) for 24 h, the expression of CysLT(1) was determined by immunostaining, Western blotting and RT-PCR.

RESULTThe pAb showed a titer of 1/32728, and was not cross-reacted with antigens of CysLT(2) receptor and GPR17. Immunostaining, Western blotting and RT-PCR analysis showed the expression of CysLT(1) receptor in BV2 microglia. Rotenone at 1μmol/L significantly induced an increased expression of CysLT(1) receptor.

CONCLUSIONThe prepared CysLT(1) receptor polyclonal antibody has a high titer and high specificity to meet testing requirements of Western blotting and immunostaining; CysLT(1) is associated with rotenone-induced injury of BV2 microglial cells.

Animals ; Cells, Cultured ; Male ; Mice ; Microglia ; drug effects ; metabolism ; pathology ; Rabbits ; Receptors, Leukotriene ; immunology ; metabolism ; Rotenone ; pharmacology

BACKGROUNDTakayasu arteritis (TA) is a rare inflammatory arteriopathy of unknown etiology. The aim of this study was to investigate the genetic susceptibility to TA in a Chinese population.

METHODSFour single nucleotide polymorphisms (SNPs) those locate in the IL12B region (rs56167332), the MLX region (rs665268), the FCGR2A/FCGR3A locus (rs10919543), and the HLA-B/MICA locus (rs12524487), associated with TA in different population, were genotyped in 123 Chinese TA patients and 147 healthy controls from January 2013 to August 2014. A Chi-square test was used to test for genotype/allele frequencies variants.

RESULTSAmong the four SNPs, rs10919543 was found to be significantly associated with TA in the studied population. The GG genotype of rs10919543 at the FCGR2A/FCGR3A locus is a high risk factor (odds ratio [OR] = 6.532, 95% confidence interval [CI] = 2.402 - 17.763, P < 0.001) for TA. Among TA patients, the level of eosinophil granulocytes (Eos) in the peripheral blood was observed to be higher in the GG group of rs10919543 (n = 23, Eos = 0.11 [0.08, 0.17] ×109/L) than the GA + AA group (n = 100, Eos = 0.08 [0.05, 0.13] ×109/L, P = 0.028). No correlation between the genotypes of the other three SNPs and TA patients was observed.

CONCLUSIONSOur findings revealed unique genetic pattern in Chinese TA patients that may be partly responsible for the higher risk of TA in this population. FCGR2A/FCGR3A-related immune disorder might contribute to the etiology of TA.

Adolescent ; Adult ; Child ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Receptors, IgG ; genetics ; Takayasu Arteritis ; etiology ; genetics

Objective: To evaluate the impact of KIT D816 mutation on the salvage therapy in relapsed acute myeloid leukemia (AML) with t(8;21) translocation. Method: The characteristics of the first relapsed AML with t(8;21) translocation from 10 hospitals were retrospectively collected, complete remission (CR(2)) rate after one course salvage chemotherapy and the relationship between KIT mutation and CR(2) rate was analyzed. Results: 68 cases were enrolled in this study, and 30 cases (44.1%) achieved CR(2). All patients received KIT mutation detection, and KIT D816 mutation was identified in 26 cases. The KIT D816 positive group had significantly lower CR(2) compared with non-KIT D816 group (23.1% vs 57.1%, χ(2)=7.559, P=0.006), and patients with longer CR(1) duration achieved significantly higher CR(2) than those with CR(1) duration less than 12 months (74.1% vs 31.9%, χ(2)=9.192, P=0.002). KIT D816 mutation was tightly related to shorter CR(1) duration. No significant difference of 2 years post relapse survival was observed between KIT D816 mutation and non-KIT D816 mutation group. Conclusion: KIT D816 mutation at diagnosis was an adverse factor on the salvage therapy in relapsed AML with t(8;21) translocation, significantly related to shorter CR1 duration, and can be used for prediction of salvage therapy response. KIT D816 mutation could guide the decision-making of salvage therapy in relapsed AML with t(8;21) translocation.
Antineoplastic Combined Chemotherapy Protocols ; Cytarabine ; Humans ; Leukemia, Myeloid, Acute/therapy* ; Prognosis ; Retrospective Studies ; Salvage Therapy

OBJECTIVETo analyze the experience with diagnosis and surgical treatment of visceral artery aneurysms (VAAs).

METHODSFrom June 2003 to December 2008, 8 patients (2 male and 6 female) with 9 VAAs underwent surgical treatment. Mean age was 49 years (ranged from 30 to 72 years). The site of aneurysmal disease was splenic artery in 4 cases, superior mesenteric artery in 2 cases, renal artery in 2 cases (3 aneurysms). In 1 patient of splenic artery aneurysm, portal vein hypertension coexisted. All the VAAs of preoperative diagnostic workup consisted of a ultrasound, computed tomography (CT) scan, and digital subtraction angiography. Six patients were operated on and two patients was treated with endovascular procedures. Only one small VAAs was treated with follow-up.

RESULTSNo deaths or major complications occurred in the perioperative period. All the patients remained symptom free during a follow-up of 26.5 months (ranged from 2 to 60 months). Follow-up consisted of clinical and ultrasound scan examinations or CT scan at 1 and 6 months, and yearly thereafter.

CONCLUSIONSAggressive approach to the treatment of VAAs is essential. Elective open surgical treatment and an endovascular procedure of visceral artery aneurysms are both safe and effective, and offers satisfactory early and long term results. There is some evidence that small (< 2 cm) and asymptomatic VAAs may be safely observed.

Adult ; Aged ; Aneurysm ; surgery ; Blood Vessel Prosthesis Implantation ; Female ; Follow-Up Studies ; Humans ; Male ; Mesenteric Artery, Superior ; pathology ; surgery ; Middle Aged ; Renal Artery ; pathology ; surgery ; Retrospective Studies ; Splenic Artery ; pathology ; surgery ; Treatment Outcome

OBJECTIVETo evaluate the efficacy of second allogeneic hematopoietic stem cell transplantation (allo-HSCT) for treatment of leukemia relapsed after first allo-HSCT.

METHODSNine patients with relapsed acute leukemia (5 AML, 4 ALL) and one with chronic myelogenous leukemia (CML) who showed cytogenetic relapse after first allo-HSCT received second allo-HSCT. The median relapse time from the first allo-HSCT was 141 days. Conditioning regimens for second allo-HSCT were combination chemotherapy based on moderate-dose Ara-C (n = 5), Bu (n = 3), conventional-dose Ara-C (n = 1) and Flud/Mel (n = 1). Prophylaxis for acute graft-versus-host disease (aGVHD) were CsA alone (n = 2), CsA/MTX (n = 1), FK506 (n = 1), and no prophylaxis in 6. The median number of peripheral blood mononuclear cells transfused was 6.1 x 10(8)/kg.

RESULTSEight cases were evaluable. All of them were engrafted and 7 developed aGVHD (grade I 4, grade II 3). The median time for absolute neutrophil count (ANC) > 0.5 x 10(9)/L and platelets > 20 x 10(9)/L were 11 and 12 days, respectively. Five cases developed localized chronic GVHD. Of all the 10 cases received second allo-HSCT, 8 died from interstitial pneumonia (n = 2), multiple-organ failure (n = 1), sepsis (n = 1), fungous pneumonia (n = 1), and leukemia relapse (n = 3), and 2 survived without leukemia for +986 and +1913 days, respectively. The leukemia free survival, transplantation related mortality and relapse rate at 2 year were 20%, 50% and 30%, respectively.

CONCLUSIONSecond allo-HSCT is a therapeutic alternative for selected patients with relapsed leukemia after first allo-HSCT.

Adult ; Disease-Free Survival ; Female ; Graft vs Host Disease ; prevention & control ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia ; pathology ; surgery ; Male ; Neoplasm Recurrence, Local ; Retrospective Studies ; Transplantation Conditioning ; methods ; Transplantation, Homologous ; Treatment Outcome

OBJECTIVETo evaluate the effectiveness, safety and feasibility of endovascular angioplasty in treating long iliac artery chronic total occlusions (CTO).

METHODSThe clinical data from a consecutive series of patients with long (> 5 cm) iliac artery CTO who treated by endovascular angioplasty from January 2006 to December 2010 was retrospectively analyzed. There were 139 patients (157 limbs) with long iliac artery CTO treated by endovascular angioplasty in this study [male 93 and female 46, mean age (77 ± 10) years]. According to TASC II classification, there were 18 patients in type B, 89 patients in type C and 32 patients in type D. Recanalization of the occluded lesions was attempted with the left brachial and/or femoral access.

RESULTSThe ankle brachial index increased from 0.42 ± 0.19 before treatment to 0.81 ± 0.26 after treatment. The rate of technical success was 96.2% (151/157) and the patency rate of iliac artery was 94.1% (111/118) during the follow-up. Significant restenosis or reocclusion was found in 7 iliac lesions and there were no major interventional complications, such as iliac artery rupture, stent displacement, pseudoaneurysms, and arteriovenous fistula.

CONCLUSIONSEndovascular angioplasty is an effective, safe and feasible method in treating long iliac CTO with high patency rate. Combined left brachial and femoral access can increase the technical success rate significantly.

Aged ; Aged, 80 and over ; Angioplasty, Balloon ; methods ; Arterial Occlusive Diseases ; surgery ; Female ; Follow-Up Studies ; Humans ; Iliac Artery ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome