BACKGROUND AND OBJECTIVEAs chemotherapy is generally used in the clinical treatment of cancer, the problem of multidrug resistance (MDR) of tumors against the chemotherapeutic agents becomes more and more serious. It has been the major cause for the failure of the chemotherapy. We detected the expressions of beta-catenin and tumor drug resistance related proteins, MRP2, P-gp, and Bcl-2, in esophageal squamous cell carcinoma (ESCC) to explore their function and correlation in the occurrence and development of MDR in ESCC.

METHODSWe used the tissue microarray technique, immunohistochemistry, and image analysis methods to detect the expressions of MRP2, P-gp, beta-catenin, and Bcl-2 proteins and analyze their relationships with clinical data in a ESCC tissue microarray consisting of 582 specimens of ESCC, 294 specimens of normal mucosa, 92 specimens of basal cell hyperplasia, and 87 specimens of dysplasia adjacent to cancer tissue.

RESULTSThe integral optical density (IOD) of MRP2 and Bcl-2, which was 195.7 +/- 175.9 x 10(3)) and 90.5 +/- 112.5 x 10(3)), respectively, was significantly higher in ESCC than in normal mucosa, which was 104.8 +/- 86.1 x103) and 25.2 +/- 46.6 x 10(3)), respectively (P < 0.01). The IOD of P-gp and beta-catenin, which was 57.7 +/- 75.5 x 10(3)) and 32.0 +/- 47.0 x 10(3)) respectively, was significantly lower in ESCC than in normal mucosa, which was 114.8 +/- 106.6 x 10(3)) and 46.1 +/- 35.7 x 10(3)), respectively (P < 0.01). According to the following order, well differentiated moderately differentiated poorly differentiated, the IOD of MRP2 increased in ESCC (P < 0.01). The IOD of beta-catenin was higher in poorly differentiated ESCC than in well or moderately differentiated ESCC (P < 0.01). The IOD of Bcl-2 was lower in well differentiated ESCC than in poorly and moderately differentiated ESCC (P < 0.01). The IOD of beta-catenin and Bcl-2 was higher in the ESCC of specimens with infiltration depths that were in membrane mucosa than those in the muscular layer or serous coat (P < 0.01). The IOD of Bcl-2 was significantly higher in cases with lymph node metastasis than in cases without (P < 0.01). Positive correlations which were respectively between the expressions of P-gp and MRP2, the expressions of P-gp and Bcl-2 were found (r = 0.288 and r = 0.253, respectively, P < 0.01).

CONCLUSIONSMRP2, P-gp, and Bcl-2 may be taken as prognostic factors for MDR of ESCC. beta-catenin may play an important role in carcinogenesis and progression of ESCC.

ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Cell Differentiation ; Esophageal Neoplasms ; metabolism ; pathology ; Female ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Multidrug Resistance-Associated Proteins ; metabolism ; Neoplasm Invasiveness ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Young Adult ; beta Catenin ; metabolism

Objective To study the different effects of valsartan and extended realse nifedipine tablets on lowering blood pressure of essential hypertension patients and their reversal effects on left ventricular hypertrophy. Methods 100 cases of essential hypertension patients with left ventricular hypertrophy were randomly divided into valsartan group(group A) and adalt group(group B).Other antihypertensive drugs except diuretic were removed for 3 weeks.There were 50 cases in group A using valsartan 4～8mg qd,and 50 cases in group B using adalt 30～60 mg qd,the stud),lasted for 24 weeks.The blood pressure was measured and the altrasowic cardiogram examed in baseline and 24 weeks later.Results BP could be significantly reduced after treatment(P

INTRODUCTION: Non-cystic fibrosis bronchiectasis (NCFB) is a highly heterogenous disease. We describe the clinical characteristics of NCFB patients and evaluate the performance of Bronchiectasis Severity Index (BSI) in predicting mortality. METHODS: Patients attending the bronchiectasis clinic between August 2015 and April 2020 with radiologically proven bronchiectasis on computed tomography were recruited. Clinical characteristics, spirometry, radiology, microbiology and clinical course over a median period of 2.4 years is presented. RESULTS: A total of 168 patients were enrolled in this prospective cohort study. They were predominantly women (67.8%), Chinese (87.5%) and never-smokers (76.9%). Median age of diagnosis was 64 years (interquartile range 56-71) and the most common aetiology was "idiopathic" bronchiectasis (44.6%). Thirty-nine percent had normal spirometries. Compared to female patients, there were more smokers among the male patients (53.8% versus 8.5%, CONCLUSION The NCFB cohort in Singapore has unique characteristics with sex differences. Over half the patients had a history of haemoptysis. The BSI score is a useful predictor of mortality in our population.
Aged ; Bronchiectasis/epidemiology* ; Cohort Studies ; Female ; Fibrosis ; Humans ; Male ; Middle Aged ; Prospective Studies ; Pulmonary Medicine ; Severity of Illness Index ; Singapore/epidemiology*

AIMTo study the biliary excretion of genistein and its metabolite at different doses in rats.

METHODSSuspended in 0.5% CMC-Na solution, genistein was orally administered to rats at the dose of 6.25, 12.5 and 50 mg x kg(-1), separately. At various time intervals, the bile was collected. The bile was treated with beta-glucuronidase. The genistein in bile was extracted twice by vortexing with 2.0 mL mixture of methyl tert-tubtyl ether and pentane (8:2). The organic phase was removed into the tubes and then evaporated in ventilation cabinet. The residue was dissolved in 50 microL of methanol. Twenty microL solution was drawn and detected by high-performance liquid chromatography.

RESULTSThe accumulative biliary excretion of genistein was (42.56 +/- 6.54) , (75.17 +/- 18.87) and (126.60 +/- 34.78) microg at the dose of 6.25, 12.5 and 50 mg x kg(-1), respectively. The total drug (genistein plus glucuronidated genistein) excreted from bile was (108.46 +/- 35.23), (423.46 +/- 158.31) and ( 853.74 +/- 320. 84) microg, and the ratio of glucuronidated genistein was 60.76% , 82.25% and 85.17% at the dose of 6.25, 12.5 and 50 mg x kg(-1), respectively.

CONCLUSIONThe genistein was excreted mainly in the form of glucuronidated genistein in rat bile. The genistein and glucuronidated genistein were excreted in a nonlinear dose-dependent manner.

Administration, Oral ; Animals ; Bile ; metabolism ; Dose-Response Relationship, Drug ; Female ; Genistein ; chemistry ; metabolism ; pharmacokinetics ; Male ; Molecular Structure ; Phytoestrogens ; administration & dosage ; metabolism ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the genetic aberrations of ocular extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type occurring in patients from southern China.

METHODSFifty seven paraffin-embedded ocular MALT lymphoma specimens from patients in southern China were studied by interphase fluorescence-in-situ hybridization (FISH) for genetic aberrations including t(11;18)(q21;q21)/API2-MALT1, t(1;14)(p22;q32)/IgH-bcl-10, t(14;18) (q32;q21)/IgH-MALT1 and bcl-6/FOXP1 gene translocations.

RESULTSAmongst the 57 cases studied, 9 cases (15.8%) showed chromosome translocations, including 4 cases (7.0%) of t(11;18)(q21;q21)/API2-MALT1, 1 case (1.8%) of t(14;18) (q32;q21)/IgH-MALT1, 1 case (1.8%) of bcl-6 gene-related chromosome translocation and 3 cases (5.3%) of IgH-unknown translocation partner. FISH revealed 17 cases (29.8%) with 3 copies of bcl-6 gene, 21 cases (36.8%) with 3 copies of MALT1 gene and 12 cases (21.1%) with 3 copies of both genes.

CONCLUSIONSThe MALT lymphoma-associated chromosome translocations t(11;18)(q21;q21)/API2-MALT1 and t(14;18) (q32;q21)/IgH-MALT1 are demonstrated in ocular MALT lymphomas of southern Chinese patients. The prevalence is significantly different from that reported in northern Chinese and northern American patients, indicating a geographic heterogeneity in the MALT lymphoma-associated genetic aberrations. The presence of 3 copies of bcl-6 and MALT1 genes is the commonest genetic abnormalities observed in ocular MALT lymphomas, suggesting a possible role in MALT lymphomagenesis.

Caspases ; genetics ; metabolism ; China ; Chromosome Aberrations ; Chromosomes, Human, Pair 11 ; genetics ; Chromosomes, Human, Pair 14 ; genetics ; Chromosomes, Human, Pair 18 ; genetics ; Chromosomes, Human, Pair 3 ; genetics ; DNA-Binding Proteins ; genetics ; metabolism ; Eye Neoplasms ; genetics ; metabolism ; Humans ; In Situ Hybridization, Fluorescence ; Lymphoma, B-Cell, Marginal Zone ; genetics ; metabolism ; Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein ; Neoplasm Proteins ; genetics ; metabolism ; Proto-Oncogene Proteins c-bcl-6 ; Translocation, Genetic ; Trisomy

Objective To assess the aMAP risk in prediction of hepatocellular carcinoma (HCC) risk in outpatients with chronic hepatitis B virus (HBV) infection. Methods A total of 709 patients with chronic HBV infection were recruited for calculation of the aMAP scores and then stratified for HCC risk statistically. The t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. Results Among these 709 patients, 22.4% had complicated with alcoholic liver disease, 11.8% with diabetes mellitus. 18.6% with fatty liver, 19.0% with liver cirrhosis, and 9.7% with liver cancer. Among all patients, 71.2% received oral antiviral medicine. Moreover, the highest aMAP score was 75.2 and the low, medium and high HCC risks were 70.0%, 23.1%, and 6.9% respectively in these patients. The proportion of patients with high HCC risk was higher among those with alcohol liver disease, diabetes mellitus, and liver cirrhosis than those without these complications (9.4% vs 6.2%; 11.9% vs 6.2%; and 19.3% vs 4.0%). The mean annual change in aMAP score was 0.93±2.05 in patients without antiviral treatment that was higher than -1.15±1.72 in patients with antiviral treatment ( t =39.36; P < 0.001). In addition, the proportion of these patients with high HCC risk three years before HCC diagnosis was 38.4%, 26.7%, and 33.3% respectively. The median of aMAP score was more than 50 three years before diagnosis liver cancer, data of which indicated that this change was earlier than that of AFP. Conclusion aMAP is a simple convenient marker for screening early HCC in outpatient with chronic HBV infection and complications, especially in those patients with alcohol liver disease, diabetes, and cirrhosis. Oral antiviral therapy could reduce aMAP in patients with chronic HBV infection.

OBJECTIVETo analyze the kinase mutation ratio, related factors, effectiveness and safety of the second generation drugs for imatinib-resistant patients with chronic myeloid leukemia(CML).

METHODSCOX proportional hazard regression model was used for unvariate and multvariate analysis of various factors affecting the kinase mutation and for evaluating the effectiveness and safety of second generation tyrosine kinase inhibitor(TKI).

RESULTS13 kinds of mutation were detected in 19 out of 42 cases for 22 times, including 4 times of F359V, 3 times of E255K, 2 time for F359C, F317L, T315I, Y253H, 1 time for D256R, C250R, D276G, F486S, M244V, Y256H and G250E, 3 cases with mixed mutations. The main adverse effects of patients receiving nilotinib were skin rash and fluid retention, while that for patients receiving dasatinib were eyelid edema and elevated bilirubin.

CONCLUSIONThe WBC count, spleen enlargement degree, chromosome karyotypes, disease staging, drug used before treatment and time of acheiving CCyR are the related factors of the kinase mutations, but the patients receiving the second generation TKI can survive well.

Objective: To investigate hypertriglyceridemia and hepatomegaly caused by Schisandrae Sphenantherae Fructus (FSS) and Schisandra chinensis Fructus (FSC) oils in mice. Methods: Mice were orally administered a single dose of Schisandrae Fructus oils. Serum and hepatic triglyceride (TG), triglyceride transfer protein (TTP), apolipoprotein B48 (Apo B48), very-low-density lipoprotein (VLDL), hepatocyte growth factor (HGF), alanine aminotransfease (ALT) and liver index were measured at 6-120 h post-dosing. Results: FSS and FSC oil caused time and dose-dependent increases in serum and hepatic TG levels, with maximum increases in the liver (by 297% and 340%) at 12 h post-dosing and serum (244% and 439%) at 24-h post-dosing, respectively. Schisandrae Fructus oil treatments also elevated the levels of serum TTP by 51% and 63%, Apo B48 by 152% and 425%, and VLDL by 67% and 38% in mice, respectively. FSS and FSC oil treatments also increased liver mass by 53% and 55% and HGF by 106% and 174%, but lowered serum ALT activity by 38% and 22%, respectively. Fenofibrate pre/ co-treatment attenuated the FSS and FSC oil-induced elevation in serum TG levels by 41% and 49% at 48 h post-dosing, respectively, but increased hepatic TG contents (by 38% and 33%, respectively) at 12 h post-dosing. Conclusions: Our findings provide evidence to support the establishment of a novel mouse model of hypertriglyceridemia by oral administration of FSS oil (mainly increasing endogenous TG) and FSC oil (mainly elevating exogenous TG).

Radiation encephalopathy is the main complication of cranial radiotherapy. It can cause necrosis of brain tissue and cognitive dysfunction. Our previous work had proved that a natural antioxidant shikonin possessed protective effect on cerebral ischemic injury. Here we investigated the effects of shikonin on carbon ion beam induced radiation brain injury in mice. Pretreatment with shikonin significantly increased the SOD and CAT activities and the ratio of GSH/GSSG in mouse brain tissues compared with irradiated group (P<0.01), while obviously reduced the MDA and PCO contents and the ROS levels derived from of the brain mitochondria. The shikonin also noticeably improved the spatial memory deficits caused by carbon ion beam irradiation. All results demonstrated that shikonin could improve the irradiated brain injury which might resulted from its modulation effects on the oxidative stress induced by the 12C6+ ion beam.
Animals ; Antioxidants ; pharmacology ; Brain Injuries ; prevention & control ; Catalase ; metabolism ; Heavy Ion Radiotherapy ; Male ; Malondialdehyde ; metabolism ; Mice ; Naphthoquinones ; pharmacology ; Protein Carbonylation ; Radiation Injuries, Experimental ; prevention & control ; Radiation-Protective Agents ; pharmacology ; Random Allocation ; Specific Pathogen-Free Organisms ; Superoxide Dismutase ; metabolism

OBJECTIVETo evaluate the clinical characteristics of multiple myeloma (MM) combined with renal amyloidosis and its curative efficacy and prognosis.

METHODSThe clinical data of 22 cases of newly diagnosed multiple myeloma combined with renal amyloidosis treated in our hospital from November 2011 to July 2015 were analyzed retrospectively.

RESULTSAccording to Intenational Staging System (ISS), among above-menthioned 22 patients the ISS II accounted for 77.2% (17/22), ISS III accounted for 22.8% (5/22). The patients with renal impairment accounted for 36.4% (8/22), with anemia 40.9% (9/22), with serum album < 35 g/L 86.4% (19/22), with urinary protein positive 100% (22/22). The evaluation of the curative efficacy of the 22 cases was as follows: CR 13.6% (3/22); VGPR 4.5% (1/22); PR 22.8% (5/22); SD 45.5% (10/22); PD 13.6% (3/22). Out of 9 patients with effective treatment, 3 cases (3/9, 33.3%) achieved "improved" in renal amyloidosis, 4 cases (4/9, 44.5%) achieved stable in renal amyloidosis, 2 cases (2/9, 2%) achieved "worsened" in renal amyloidosis. Among 17 cases who were followed up, 7 cases died, 10 cases survived, the average duration of follow-up for these cases was 11 (1-37) months, the median overall survival (OS) time was 19 (95% CI 9.2-28.8) months.

CONCLUSIONMM with renal amyloidosis is rare, refractory and has a poor prognosis. Whether there is impairment of kidney function or not, renal amyloidosis shall be taken into consideration if the MM patients got massive proteinuria especially nephritic syndrome. Bortezomib may improve the curative efficacy.

Amyloidosis ; diagnosis ; pathology ; therapy ; Bortezomib ; therapeutic use ; Humans ; Kidney Diseases ; diagnosis ; pathology ; therapy ; Multiple Myeloma ; diagnosis ; pathology ; therapy ; Prognosis ; Proteinuria ; diagnosis ; Retrospective Studies ; Treatment Outcome