Objective: To compare the detection rate of arrhythmia in chronic heart failure (CHF) patients by different time of ambulatory electrocardiogram (Holter). Methods: A total of 108 consecutive elderly CHF patients received 72h Holter in our hospital from 2016-01 to 2016-09 were enrolled. According to NYHA classification, LVEF and plasma NT-proBNP level, the patients were divided into 3 sets of groups. Detection rates of supra-ventricular arrhythmia and ventricular arrhythmia were compared among 24h, 48h and 72h Holter recording. Results: Based on NYHA classification, the patients were divided into 3 groups: NYHA Ⅱ group, n=24, NYHAⅢ group, n=42 and NYHAⅣ group, n=26; based on NT-proBNP level, the patients were divided into 2 groups: NT-proBNP≥1000 pg/ml group and NT-proBNP<1000 pg/ml group, n=54 in each group; based on LVEF, the patients were divided into 3 groups: HFpEF group, n=80, HFmrEF group, n=13 and HFrEF group, n=15. Detection rate for non-sustained atrial tachycardia (NSAT) was 81.7% by 48h Holter which was higher than 64.6% at 24h, P<0.01; for non-sustained ventricular tachycardia (NSVT) was 38% at 72h which was higher than 25.9% at 24h, P<0.01. For new-onset paroxysmal atrial fibrillation, only 1 patient was detected by 24h Holter and the additional 3 patients were detected by 72h. Group analysis indicated that the detection rate of NSVT was different by 72h and 24h Holter in NYHA Ⅲ patients, P<0.05; while it was similar in NYHA Ⅳ patients, P>0.05. Conclusion: Long term (72h/48h) Holter had the higher detection rate of arrhythmia in HF patients, 24 h monitoring was easier to find NSVT in severer HF patients. In moderate to severe HF patients, the detection time may be prolonged if NSVT couldn't be found by 24h Holter which was helpful for clinical treatment.

BACKGROUNDGrowing preclinical evidence shows that zoledronic acid (ZOL) exhibits direct antitumor activity in various cancer cell lines. However, the cytotoxic effects of ZOL on human hepatocellular carcinoma (HCC) cells have not been established. In the present study, we investigated the effect of ZOL on HCC both in vitro and in vivo.

METHODSCytotoxicity and cell cycles were assessed with Sulforhodamine B colorimetric assay and flow cytometry. Expression levels of cell cycle phase-linked proteins were examined. The effect of ZOL on HCC in vivo was explored based on H22-subcutaneous injection (s.c.) and H22-intraperitoneal injection (i.p.) mice model.

RESULTSZOL inhibited the growth of SK-HEP-1 and H22 cells and induced S-phase arrest through downregulating cdc2 protein and upregulating cyclin A. It inhibited the growth of s.c tumors, and increased the survival of both H22-s.c. and H22-i.p. mice in vivo.

CONCLUSIONZOL inhibits growth of HCC cells in vitro and in vivo.

Animals ; Carcinoma, Hepatocellular ; drug therapy ; pathology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Diphosphonates ; pharmacology ; therapeutic use ; Female ; Humans ; Imidazoles ; pharmacology ; therapeutic use ; Liver Neoplasms ; drug therapy ; pathology ; Mice ; Xenograft Model Antitumor Assays

AIM To establish an HPLC method for the simultaneous content determination of ginsenoside Re,ginsenoside Rg1,ginsenoide Rb1,specnuezhenide,calycosin-7-O-β-D-glucoside and oleanolic acid in Yitai Cap sules (Ginseng Radix et Rhizoma,Astragali Radix,Ligustri lucidi Fructus,etc.).METHODS The analysis of 70％ ethanol extract of this drug was performed on a 25 ℃ thermostatic Luna C18 column (4.6 mm ×250 mm,5 μm),with the mobile phase comprising of methanol-O.2％ phosphoric acid flowing at 1.0 mL/minin a gradient elution manner,and the detection wavelength was set at 203 nm.RESULTS Six constituents showed good linear relationships within their own ranges (r ＞ 0.999 0),whose average recoveries were 95.58％-102.12％ with the RSDs of 0.82％-1.73％.CONCLUSION This simple and stable method can be used for the rapid quality control of Yitai Capsules.

OBJECTIVETo evaluate the diagnostic role of nuclear expression of bcl-10 protein in extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type.

METHODSOne hundred and forty cases of MALT lymphoma were collected from Cancer Hospital of Fudan University (including 38 cases from stomach, 35 cases from ocular adnexa, 16 cases from intestine, 15 cases from skin, 15 cases from salivary gland, 14 cases from lung, 3 cases from thyroid and 4 cases from other sites). Ten cases of reactive follicular hyperplasia of tonsil, 5 cases of reactive lymphoid hyperplasia of orbit and 143 cases of non-Hodgkin's lymphoma other than MALT lymphoma (including 20 cases of NK/T cell lymphoma, 20 cases of follicular lymphomas, 20 cases of anaplastic large cell lymphomas, 20 cases of nodal diffuse large cell B-cell lymphoma (DLBCL), 10 cases of gastric diffuse large B-cell lymphoma, 13 cases of nodal marginal zone B-cell lymphoma, 12 cases of mantle cell lymphoma, 11 cases of splenic marginal zone B-cell lymphoma, 6 cases of angioimmunoblastic T-cell lymphoma, 6 cases of peripheral T-cell lymphoma, not otherwise specified, 3 cases of small lymphocytic lymphoma, 1 case of lymphoplasmacytic lymphoma and 1 case of plasmacytoma were used as controls. Immunohistochemical study for bcl-10, as well as dual staining with CD20, was performed by EnVision method in paraffin sections.

RESULTSIn reactive follicular hyperplasia of tonsil, bcl-10 was moderately or strongly expressed in the cytoplasm of germinal center B cells, while the mantle cells were negative and the marginal zone cells and paracortical T cells showed weak staining. In the 5 cases of reactive lymphoid hyperplasia of orbit, 2 were bcl-10-negative and the remaining 3 expressed bcl-10 in the cytoplasm of germinal center B cells. As for non-MALT lymphomas, 3 gastric DLBCL showed nuclear expression. The remaining cases showed variable cytoplasmic staining. In some cases of lymphoma, bcl-10 was expressed in tumor cells but not in reactive lymphoid cells. On the other hand, 92.1% (129/140) of MALT lymphoma were bcl-10 positive. Among those cases, 54.3% (76/140) showed cytoplasmic positivity and 37.9% (53/140) showed nuclear positivity. The nuclear positivity rate of bcl-10 in different anatomic sites was different. The staining was most intense in MALT lymphoma of ocular adnexa. Dual staining with CD20 showed that the bcl-10-positive cells were also CD20-positive, though the number of bcl-10-positive cells were less than that of CD20-positive cells.

CONCLUSIONSBcl-10 expression in lymphoid hyperplasia is a universal phenomenon. Cytoplasmic expression of bcl-10 is seen in many different kinds of non-Hodgkin's lymphoma and reactive lymphoid conditions. In some cases of lymphoma, bcl-10 is expressed in tumor cells but not in reactive lymphoid cells, suggesting a possible role of abnormal bcl-10 expression in tumorgenesis. Nuclear expression of bcl-10 is seen mainly in MALT lymphoma, especially when occurring in ocular adnexa and lung. This is in contrast to loss of bcl-10 expression in residual germinal center cells.

Adaptor Proteins, Signal Transducing ; genetics ; Antigens, CD20 ; immunology ; B-Cell CLL-Lymphoma 10 Protein ; Cell Nucleus ; genetics ; Cytoplasm ; genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Lymphocytes ; pathology ; Lymphoma, B-Cell, Marginal Zone ; genetics ; immunology ; pathology ; Palatine Tonsil ; pathology ; Pseudolymphoma ; genetics

An improved and practical synthesis of racemic 11-demethylcalanolide A [(+/-)-1] was developed. This improved process involved Pechmann reaction on phloroglucinol with ethyl butyrylacetate to give 5,7,-dihydroxy4-n-propylcoumarin (3). Poly phosphoric acid (PPA) catalyzed acylation of compound (3) with crotonic acid, then intramolecular cyclization was achieved simultaneously in one step to afford the key intermediate chromanone (4). A microwave assisted synthetic method preparing chromene (6) using chromenynation of chromanone (4) with 1, 1-diethoxy-methyl-2-butene was conducted. Luche reduction of chromene (6) using NaBH4 with CeCl3 x 7H2O preferably gave (+/-)-1. The overall yield of this four step synthesis of (+/-)-1 was around 32% increasing one fold more than that of the previous method. An in vitro investigation showed that (+/-)-1 exhibited inhibitory activities against both wild-type and drug-resistant HIV-1 in HIV-1 RT and cell culture assay, and significant synergistic effects in combination with AZT, T-20, and indinavir. Its LD50 of acute toxicity in mice by intragastric administration and by intraperitoneal injection were 735.65 mg kg(-1) and 525.10 mg x kg(-1), respectively. The Cmax and AUC(0-infinity) were 0.54 microg x mL(-1) and 1.08 (microg x mL(-1) x h, respectively. The dynamics study of the inhibition of mice sera on HIV-1 RT showed that mice treated with 100 mg x kg(-1 (+/-)-1 once intraperitoneally were similar to that of 5 mg x kg(-1) of known clinical effective anti-HIV-1 drug neverapine. The results suggested that further investigation of the anti-HIV candidate (+/-)-1 was warranted.
Animals ; Anti-HIV Agents ; chemical synthesis ; immunology ; pharmacology ; toxicity ; Drug Synergism ; HIV Reverse Transcriptase ; metabolism ; HIV-1 ; drug effects ; enzymology ; Humans ; Immune Sera ; pharmacology ; Indinavir ; pharmacology ; Lethal Dose 50 ; Male ; Mice ; Pyranocoumarins ; chemical synthesis ; immunology ; pharmacology ; toxicity ; Reverse Transcriptase Inhibitors ; chemical synthesis ; immunology ; pharmacology ; toxicity ; Zidovudine ; pharmacology

OBJECTIVETo study the frequency of certain specific genetic aberrations, including t (11; 18)/API2-MALT1, t (1; 14)/IgH-bcl-10 and t (14; 18)/IgH-MALT1, in mucosa-associated lymphoid tissue (MALT) lymphoma of different sites.

METHODSOne hundred and ninety-six cases of MALT lymphoma from Cancer Hospital of Fudan University were enrolled into the study. The samples consisted of MALT lymphomas from stomach (53 cases, including 44 cases of low-grade MALT lymphoma and 9 cases of MALT lymphoma with diffuse large B-cell lymphoma component), ocular adnexa (50 cases), salivary gland (20 cases), lung (20 cases), intestine (17 cases), skin (17 cases), liver (8 cases), thyroid (5 cases) and other sites (2 cases from tongue, 1 case from pancreas, 1 case from larynx, 1 case from vocal cords and 1 case from kidney). Fluorescence in-situ hybridization for API2-MALT1 fusion gene, bcl-10, MALT1 and IgH genes was performed on paraffin sections.

RESULTSAmong the 196 cases of MALT lymphoma, 25 cases (12.8%) possessed API2-MALT1 fusion gene. The positive rates in various sites were significantly different (P = 0.002), as follows: 45.0% (9/20) in lung, 22.7% (10/44) in stomach (without large cell component), 15.0% (3/20) in salivary gland, 2 of 17 cases in intestine and 2.0% (1/50) in ocular adnexa. The fusion gene was not detected in the 9 cases of gastric MALT lymphoma with large cell transformation. It was also negative in the MALT lymphomas from skin, thyroid and other sites. One of the pulmonary MALT lymphoma cases showed simultaneous aberrations of IgH and MALT1 genes, such as t (14; 18)/IgH-MALT1. Two of the gastric MALT lymphoma cases without large cell transformation and one of the pulmonary MALT lymphoma cases showed aberrations in both IgH and bcl-10 genes, such as t (1; 14)/IgH-bcl-10. Six cases of MALT lymphoma, including 2 cases from salivary gland, 2 cases from liver, 1 case from thyroid and 1 case from stomach (large cell transformation), showed trisomy 18. On the other hand, 3 cases, including 2 cases from stomach and 1 case from intestine, showed MALT1 gene amplification.

CONCLUSIONSIn general, specific genetic aberrations have a relatively low frequency of occurrence in MALT lymphomas. The positive rates however show a remarkable difference in tumors of different anatomic sites. This phenomenon may suggest that MALT lymphomas in different sites, though sharing similar morphologic features, may have a divergent tumorgenesis.

Adaptor Proteins, Signal Transducing ; genetics ; Animals ; B-Lymphocytes ; pathology ; Chromosomes, Human, Pair 18 ; Genes ; Humans ; In Situ Hybridization, Fluorescence ; methods ; Lymphoma, B-Cell ; genetics ; Lymphoma, B-Cell, Marginal Zone ; genetics ; Lymphoma, Large B-Cell, Diffuse ; genetics ; Neoplasm Proteins ; genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Translocation, Genetic ; Trisomy

OBJECTIVETo explore the effect of puerarin combined with felodipine on the mRNA and protein expression of apelin and APJ in renal tissue of renovascular hypertensive rat.

METHODSixty-two Sprague-Dawley rats were used, of which 8 rats were randomly chosen as sham-operation group. The remaining rats were made for the rat model with renovascular hypertension. The renovascular hypertensive rats were randomly divided into 5 groups as follows: 4 groups which were treated with felodipine (0.8 mg x kg(-1) x d(-1)), puerarin (50 mg x kg(-1) x d(-1)), puerarin combined with felodipine (puerarin 25 mg x kg(-1) x d(-1) + felodipine 0.4 mg x kg(-1) x d(-1)) or captopril combined with felodipine (captopril 15 mg x kg(-1) x d(-1) x felodipine 0.4 mg x kg(-1) x d(-1)), and 1 group which was treated with distilled water. Drugs or distilled water were administered for 8 weeks. The expression of apelin and APJ mRNA and protein in ischemic and non-ischemic kidneys was assessed by RT-PCR or Western blot.

RESULTCompared with sham-operation group, the expression of apelin mRNA and protein in ischemic and non-ischemic kidneys in model group was increased significantly (P < 0.01); the expression of APJ mRNA and protein in ischemic kidneys had no significance, while that in non-ischemic kidneys was decreased (P < 0. 01). Compared with model group, the expression of apelin mRNA and protein in ischemic and non-ischemic kidneys was decreased significantly in all drug-treated groups (P < 0.01); while that of APJ mRNA and protein in non-ischemic kidneys was upregulated (P < 0.01). Compared with felodipine group, the expression of apelin mRNA and protein in ischemic and non-ischemic kidneys was decreased (P < 0.01 or P < 0.05) in the group treated with both puerarin and felodipine; and the expression of APJ mRNA and protein in ischemic kidneys did not reach significant level, however, that was upregulated in non-ischemic kidneys (P < 0.01 or P < 0.05).

CONCLUSIONPuerarin downregulates the expression of apelin mRNA and protein in ischemic and non-ischemic kidneys, and upregulates that of APJ mRNA and protein in non-ischemic kidneys. Combination of puerarin and felodipine enhances the above-mentioned effects and shows no significant difference versus the combination of felodipine and captopril. The results suggest that puerarin regulates blood pressure and protects target organ through apelin/APJ pathway and that puerarin has synergetic effects with CCB.

Animals ; Antihypertensive Agents ; pharmacology ; Apelin ; Apelin Receptors ; Blotting, Western ; Captopril ; pharmacology ; Drug Synergism ; Felodipine ; pharmacology ; Gene Expression ; drug effects ; Hypertension, Renovascular ; genetics ; metabolism ; Intercellular Signaling Peptides and Proteins ; genetics ; metabolism ; Ischemia ; Isoflavones ; pharmacology ; Kidney ; blood supply ; drug effects ; metabolism ; Male ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, G-Protein-Coupled ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Vasodilator Agents ; pharmacology

AIMTo study the alkaline-degradation products of ginsenosides from leaves and stems of Panax quinquefolium L.

METHODSIsolation and purification were carried out on silica gel and HPLC; the structures of chemical constituents were elucidated by spectral analysis.

RESULTSFrom the alkaline-degradation products, nine compounds were identified as: 20 (S) -protopanaxadiol (I), 20 (S) -dammar-25 (26)-ene-3beta, 12beta, 20-triol (II), 24 (R) -ocotillol (III), 20 (S) -protopanaxatriol (IV), 20 (S) -dammar-25 (26)-ene-3beta, 6alpha, 12beta, 20-tetrol (V), dammar-20 (21), 24-diene-3beta, 12beta-diol (VI), dammar-20(21), 24-diene-3beta, 6alpha, 12beta-triol (VII), 20 (S), 24 (S) -dammar-25 (26) -ene-3beta, 6alpha, 12beta, 20, 24-pentanol (VIII), 20 (S) -dammar-23-ene-25-hydroperoxyl-3beta, 6alpha, 12beta, 20-tetrol (IX).

CONCLUSIONThe configuration of C20 position of ginsenosides was not changed by alkaline-degradation. The complete assignments of 1H and 13C NMR chemical shifts of four new compounds V, VII, VIII, IX, were acquired by means of 2D NMR spectra. Compound I showed antitumor effect on human colon carcinoma cells in vitro.

Antineoplastic Agents, Phytogenic ; isolation & purification ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Colonic Neoplasms ; pathology ; Ginsenosides ; isolation & purification ; metabolism ; Humans ; Molecular Conformation ; Molecular Structure ; Panax ; chemistry ; Plant Leaves ; chemistry ; Plant Stems ; chemistry ; Plants, Medicinal ; chemistry ; Sapogenins ; chemistry ; isolation & purification ; pharmacology ; Triterpenes ; chemistry ; isolation & purification ; pharmacology

OBJECTIVE: To study the predictive value of Pediatric Age-adapted Sequential Organ Failure Assessment Score (pSOFA), Pediatric Risk of Mortality Score III (PRISM III), and Pediatric Critical Illness Score (PCIS) in children with severe sepsis. METHODS: A retrospective analysis was performed for the clinical data of 193 hospitalized children with severe sepsis. According to the final outcome, these children were divided into a survival group with 151 children and a death group with 42 children. The scores of pSOFA, PRISM III, and PCIS were determined according to the worst values of each index within 24 hours after admission. The receiver operating characteristic (ROC) curve was used to analyze the efficiency of each scoring system in predicting the risk of death due to sepsis. Smooth curve fitting was used to analyze the correlation between the three scoring systems and the threshold effect of each scoring system. Decision curve analysis (DCA) was used to evaluate the application value of each scoring system. RESULTS: The ROC analysis showed that PCIS and pSOFA had a similar predictive value (P=0.182) and that PRISM III and pSOFA had a similar predictive value (P=0.210), while PRISM III had a better predictive value than PCIS (P=0.045). PRISM III had the highest degree of fitting with prognosis, followed by pSOFA and PCIS. The DCA analysis showed that when the risk of death was 0.4 and 0.6 in children with severe sepsis and the three scoring systems were used as the basis for emergency intervention decision-making, pSOFA achieved the highest standardized net benefit, followed by PRISM III and PCIS. CONCLUSIONS All three scoring systems have a certain value in predicting the prognosis of children with severe sepsis, and pSOFA has a better value than PRISM III and PCIS.
Child ; Critical Illness ; Humans ; Organ Dysfunction Scores ; Prognosis ; ROC Curve ; Retrospective Studies ; Sepsis

OBJECTIVELcrV is an important component for the development of a subunit vaccine against plague. To reduce immunosuppressive activity of LcrV, a recombinant LcrV variant lacking amino acids 271 to 326 (rV270) was prepared by different methods in this study.

METHODSA new strategy that produced non-tagged or authentic rV270 protein was designed by insertion of rV270-thrombin-hexahistidine fusion gene into the vector pET24a, or by insertion of hexahistidine-enterokinase-rV270 or hexahistitine-factor Xa-rV270 fusion gene into the vector pET32a. After Co(2+) affinity chromatography, a purification strategy was developed by cleavage of His tag on column, following Sephacryl S-200HR column filtration chromatography.

RESULTSRemoval of His tag by thrombin, enterokinase and factor Xa displayed a yield of 99.5%, 32.4% and 15.3%, respectively. Following Sephacryl S-200HR column filtration chromatography, above 97% purity of rV270 protein was obtained. Purified rV270 that was adsorbed to 25% (v/v) Al(OH)₃ adjuvant in phosphate-buffered saline (PBS) induced very high titers of antibody to rV270 in BALB/c mice and protected them (100% survival) against subcutaneous challenge with 10⁶ CFU of Y. pestis virulent strain 141.

CONCLUSIONThe completely authentic rV270 protein can be prepared by using enterokinase or factor Xa, but they exhibited extremely low cleavage activity to the corresponding recognition site. Thrombin cleavage is an efficient strategy to prepare non-tagged rV270 protein and can be easily operated in a large scale due to its relatively low cost and high cleavage efficacy. The recombinant rV270 can be used as a key component to develop a subunit vaccine of plague.

Amino Acid Sequence ; Animals ; Antibodies, Bacterial ; blood ; Antigens, Bacterial ; genetics ; immunology ; Blotting, Western ; Cloning, Molecular ; Electrophoresis, Polyacrylamide Gel ; Escherichia coli ; genetics ; Female ; Genetic Vectors ; Mice ; Mice, Inbred BALB C ; Molecular Sequence Data ; Plague ; immunology ; prevention & control ; Plague Vaccine ; genetics ; immunology ; Plasmids ; Pore Forming Cytotoxic Proteins ; genetics ; immunology ; Protein Engineering ; methods ; Recombinant Fusion Proteins ; genetics ; immunology ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Survival Analysis ; Vaccines, Subunit ; genetics ; immunology ; Yersinia pestis ; growth & development ; immunology