[Advances in warfarin's anticoagulation therapy in Chinese population after mechanical valve replacement].

Warfarin is an irreplaceable oral anticoagulant for patients with mechanical heart valves, the stable pharmacogenetic-based warfarin dose prediction algorithms have improved the effectiveness and safety of warfarin anticoagulation therapy. Genetic factors are the main factors affecting the stable dose of warfarin. Single nucleotide polymorphisms such as VKORC1 and CYP2C9 affect the anticoagulation effect of warfarin through pharmacodynamic or pharmacokinetic pathways. Age, body surface area, combined use of drugs, and other nongenetic factors also affect the stable dose of warfarin. Previously published algorithms for warfarin dose prediction included mainly the white race, and most algorithms were constructed using traditional multiple linear regression. However, domestic studies have used machine learning methods to construct warfarin dose prediction algorithms based on the Chinese Han post-mechanical valve replacement population and have achieved better prediction efficiency. This article reviews the advances of warfarin anticoagulation influencing factors and the clinical application of stable dose prediction algorithms.

MiR-185-3p downregulates advanced glycosylation end product receptor expression and improves renal function in diabetic nephropathy mice.

OBJECTIVE: To investigate the effects of the downregulation of AGER by miRNA-185-3p on renal function in diabetic nephropathy (DN) mice. MATERIALS AND METHODS: Mice were divided into normal, model, NC, miR-185-3p mimic, si-AGER, and miR-185-3p mimic + si-AGER groups. Eight weeks following the establishment of the model, various indicators were assessed. RESULTS: Compared to control groups, miR-185-3p expression, body weight, superoxide dismutase (SOD) content, catalase (CAT) content, proliferation, S-phase ratios, and proliferating cell nuclear antigen (PCNA) expression were significantly lower in all experimental groups, whilst AGER expression, water intake, food intake, urine volume, urine protein content, serum creatinine (Scr), Blood Urea Nitrogen (BUN), MDA content, G0/G1 status, and rates of apoptosis were significantly higher (all p<0.05). Compared to the model group, miR-185-3p mimics, si-AGER, and miR-185-3p mimic + si-AGER groups had a significantly higher SOD content, CAT content, proliferation, S phase ratios, PCNA expression and lower AGER expression, water intake, food intake, urine output, urine protein, Scr, BUN, MDA content, G0/G1 ratios, and apoptosis rates (all p<0.05). In addition, the effects of the miR-185-3p mimics + si-AGER were superior to miR-185-3p mimics and si-AGER monotherapy groups (both p<0.05). CONCLUSIONS: MiR-185-3p inhibits AGER, downregulates AGER expression, and improves renal function in DN mice.

Prediction of protein-protein interactions using chaos game representation and wavelet transform via the random forest algorithm.

Studying the network of protein-protein interactions (PPIs) will provide valuable insights into the inner workings of cells. It is vitally important to develop an automated, high-throughput tool that efficiently predicts protein-protein interactions. This study proposes a new model for PPI prediction based on the concept of chaos game representation and the wavelet transform, which means that a considerable amount of sequence-order effects can be incorporated into a set of discrete numbers. The advantage of using chaos game representation and the wavelet transform to formulate the protein sequence is that it can more effectively reflect its overall sequence-order characteristics than the conventional correlation factors. Using such a formulation frame to represent the protein sequences means that the random forest algorithm can be used to conduct the prediction. The results for a large-scale independent test dataset show that the proposed model can achieve an excellent performance with an accuracy value of about 0.86 and a geometry mean value of about 0.85. The model is therefore a useful supplementary tool for PPI predictions. The predictor used in this article is freely available at http://www.jci-bioinfo.cn/PPI.

Increased Th17 cells contribute to disease progression in patients with HBV-associated liver cirrhosis.

T helper (Th) 17 cells have been demonstrated to participate in the pathogenesis of HBV-associated liver damage. However, little is known regarding the immunopathogenic role of liver fibrosis in patients with HBV-associated liver cirrhosis. The aims of this study were to evaluate whether Th17 cells are related to disease progression in patients and to explore the possible mechanisms. The frequencies of circulating Th17 cells were analysed in 78 patients with hepatitis B and cirrhosis (Child A: 34; Child B: 22; Child C 22) and matched controls. Liver samples were collected from 13 patients with HBV-associated cirrhosis, 23 patients with chronic hepatitis B and 12 healthy controls for immunohistochemical analysis. IL-17 receptor expression was studied on liver biopsies and in human hepatic stellate cells as well as their response to recombinant IL-17 by flow cytometry. Patients with hepatitis B-associated cirrhosis with more severe disease displayed significant increases in peripheral numbers of Th17 cells as well as in IL-17 plasma levels. The increased intrahepatic IL-17(+) cells correlated positively with fibrotic staging scores and clinical progression from CHB to cirrhosis. Moreover, many IL-17(+) cells were located in fibrotic areas in the liver of patients with cirrhosis. In vitro, IL-17 together with IL-17-activated monocytes, could promote the activation of stellate cells, which, in turn, aggravated liver fibrosis and the inflammatory response. In summary, increased peripheral and intrahepatic Th17 cells are enriched in patients with hepatitis B and cirrhosis and contribute further to the severity of disease progression through induction of stellate cell activation.

Changes in blood oxidative and antioxidant parameters in a group of Chinese patients with age-related macular degeneration.

OBJECTIVE: To measure the oxidative and antioxidant biochemical parameters in the serum of Chinese patients with age-related macular degeneration (AMD) and in a similar age control group from the same area. DESIGN: A case-control study. PARTICIPANTS: 56 AMD patients ( 21 early dry, 13 geographic atrophy and 22 wet form) and 34 normal subjects, similar for age and sex were studied. MEASUREMENTS: Both groups completed a questionnaire about demographic characters and dieatry habit, and the levels of serum lipid peroxidation (malondialdehyde, MDA) and antioxidants parameters (vitamin C and E, the activities of superoxide dismutase--SOD, total antioxidant capacity--TAC ) were determined. RESULTS: There was a significantly higher frequency of daily intake of fruit and legumes in controls than in AMD patients. There was a significantly increased serum MDA levels and SOD activities, and significantly decreased serum vitamin C and total antioxidant capacity in AMD patients as compared to controls. The intensity of lipid peroxidation was higher with the progression of AMD. There was not difference in serum vitamin E levels between AMD patients and controls. CONCLUSION: Oxido-reduction disturbance may be involved in the pathogenesis of AMD. There is a significantly decreased antioxidant capacity in AMD patients.

Pentoxifylline downregulates nitric oxide and tumor necrosis factor-alpha induced by mycobacterial lipoarabinomannan in a macrophage cell line.

Pentoxifylline (PTX), a phosphodiesterase inhibitor, is known to downregulate tumor necrosis factor-alpha (TNF-alpha) secretion induced by lipopolysacchride (LPS) and gamma interferon (IFN-gamma). We have had limited success in treating leprosy reactions, including erythema nodosum leprosum (ENL), in which TNF-alpha has been identified as a major proinflammatory cytokine. PTX inhibited production of NO (IC50 approximately equal to 1.0 mg/ml) and TNF-alpha (IC50 approximately equal to 0.05 mg/ml) in a dose-dependent fashion. As little as 0.5 mg/ml of PTX decreased NO production and 0.01 mg/ml of PTX inhibited TNF-alpha production. Western blot analyses demonstrated that iNOS was suppressed by PTX. Northern blot analyses showed significant reduction of TNF-alpha mRNA. We conclude that PTX is an effective inhibitor of lipoarabinomannan (LAM)-induced TNF-alpha production at both the product and transcriptional levels in our macrophage cell line. PTX also showed moderate inhibition of NO at the product level as well as translation of iNOS.

[AFLP analysis of photoperiod-sensitive genic male sterile(PGMS) rice mutant lines].

The reaction conditions for rice AFLP assay were optimized. The relative efficiencies for polymorphism detection of RFLP, RAPD and AFLP were compared through the analysis between a pair of PGMS allelic mutant lines(NK58S and NK58F). Results indicated that the efficiency for polymorphism detection in rice is in the order of AFLP > RAPD > RFLP, and also indicated that AFLP is a powerful DNA molecular marker technique for polymorphism detection, especially in the cases of extremely low polymorphism, such as isogeneic lines and allelic mutant lines. The advantages and disadvantages of these three molecular marker systems were discussed. Using AFLP in conjunction with bulked segregating analysis, 5106 AFLP loci were screened and 9 of them showed polymorphism between NK58S and NK58F, 4 of the polymorphic AFLP products were cloned, Southern bloting analysis showed that two of them were single copy sequences while the other two were low copy sequences in rice genome.

Taxonomic relationships among the taxa in the Candida guilliermondii complex, as revealed by comparative electrophoretic karyotyping.

Electrophoretic karyotypes of 15 type strains of the taxa in the Candida guilliermondii complex including Candida fukuyamaensis Nakase et al. and Candida xestobii Yarrow et S. A. Meyer were comparatively analysed by using the CHEF (contour-clamped homogeneous electric field) method of PFGE. Eighteen strains (isolated from various natural sources in China) which were originally identified as C. guilliermondii by conventional methods were also included. Six electrophoretic karyotype groups were recognized among the strains compared. The following type strains were grouped together with the type strains of C. guilliermondii (Castellani) Langeron et Guerra and Pichia guilliermondii Wickerham: Blastodendrion arztii Ota, Blastodendrion krausi Ota, Candida amidovorans Balloni et al., C. guilliermondii var. japonica Sugiyama et Goto, Candida mamillae S. Goto, Candida parapsilosis (Ashford) Langeron et Talice var. tokyoensis Suzuki et al., C. parapsilosis var. tuxtlensis Herrera et al. and six Chinese strains. The type strain of Torulopsis kestonii Scarr et Rose was classified into the group together with the type strain of Candida fermentati (Saito) Bai and seven Chinese strains. The group represented by the type strain of C. fukuyamaensis included five other strains isolated in China. The type strains of Candida xestobii, C. guilliermondii var. carpophila Phaff et M. W. Miller and Trichosporon appendiculare Batista et al. were separated into three different groups, respectively. Taxonomic relationships among the taxa studied are discussed.

Preliminary study of oral polylactide microcapsulated insulin in vitro and in vivo.

AIM: Although the oral route for insulin delivery is the most convenient, directly administered oral insulin is degraded by proteolytic enzymes in the gastrointestinal (GI) tract. Polylactide was prepared in order to microcapsulate the insulin to avoid the enzymes in the GI. The physical characteristics and therapeutic possibilities of polylactide microcapsulated insulin (PLA-MCI) were studied in vivo and in vitro. METHODS: PLA-MCI was prepared by the two-step method of emulsion and solvent extraction. Its morphologic character was observed by scanning electron microscopy (SEM). The insulin release profile was determined in vitro by insulin measurement and in vivo by blood glucose measurement after the force-feeding of 66 diabetic rats. RESULTS: When the microcapsule was spherical in shape (diameter 1.5-2.0 microm) the entrapment efficiency of insulin was 90% and the loading rate was 10% (W/W). The PLA-MCI (which contained 3.0 units of insulin/mg of PLA) had peak release rates of 65-74% over 6-8 h in phosphate buffer. The same dose of PLA-MCI (insulin 2.5 mg) led to decreased responses (from 28% to 68% of control blood glucose levels) in the level of blood glucose in 32 rats which had not fasted after they had been force-fed. When 1.2, 1.8, 2.2 and 3.0 mg of insulin + PLA-MCI was administered to eight diabetic rats, their blood glucose levels decreased by 28%, 36%, 54% and 78%, respectively. CONCLUSIONS: PLA microcapsules are capable of protecting insulin from degradation by the proteolytic enzymes in the GI and of alleviating hyperglycaemia for a prolonged period of time in diabetic rats. It may therefore be considered as a new carrier for oral insulin.

Preactivation exposure of RAW 264.7 cells to taurine chloramine attenuates subsequent production of nitric oxide and expression of iNOS mRNA.

Recent studies demonstrate that taurine chloramine (Tau-Cl) inhibits production of nitric oxide (NO) and other proinflammatory mediators in cultured macrophages when added to the media at the time of activation. Because Tau-Cl may react with various media constituents and it is difficult to measure Tau-Cl in complex solutions, we designed experiments to more carefully control cell exposure to various chloramines and NaOCl. RAW 264.7 cells were exposed to 1 mM of NaOCl, Tau-Cl, or chloramine preparations of the following amino acids: L-alanine (L-Ala-Cl), beta-alanine (beta-Ala-Cl), serine (Ser-Cl), or glycine (Gly-Cl) in Hanks' balanced salt solution (HBSS) for up to 2 h (37 degrees C, 5% CO2). The HBSS solution was then replaced with complete media containing interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS) for an additional 24 h before measuring cell viability. The chemical stability of NaOCl and each chloramine was evaluated after various times of preactivation exposure by measuring retention of each solution's UV absorption spectra and ability to oxidize KI. Cytotoxicity of each solution was evaluated by the maintained ability of RAW 264.7 cells to reduce MTT. Whereas Tau-Cl, beta-Ala-Cl, and Gly-Cl were stable chloramines, only Tau-Cl was not cytotoxic. L-Ala-Cl, Ser-Cl, and the highly reactive oxidant NaOCl were unstable and toxic. In further studies RAW 264.7 cells were exposed to Tau-Cl in HBSS for 2 h and the solution was then replaced with complete media containing IFN-gamma and LPS, taxol, lipoarabinomannan, or interleukin-2. Production of NO was measured 24 h later and was inhibited in activated cells that were previously exposed to Tau-Cl. Inhibition of NO production was dependent on Tau-Cl concentration and was accounted for by reduced expression of inducible nitric oxide synthase mRNA, regardless of activator combinations. These results support the idea that Tau-Cl has the potential to function as an inhibitory modulator of inflammations.

Endoscopic Nd:YAG laser therapy in patients with early superficial carcinoma of the esophagus and the gastric cardia.

A group of 33 patients, 27 with early superficial esophageal cancer and six with early superficial carcinoma of the gastric cardia, were treated with endoscopic neodymium:yttrium aluminum garnet (Nd:YAG) laser from April 1989 to March 1993. Of the 33 patients, in 32 (97%) the disappearance of the cancer cells was noted. They were treated 1-6 times (average 2.6) with laser irradiation. No serious complications, such as perforation, occurred in the series. Twenty-two patients were followed up for 24-55 months. A negative biopsy was recorded in 16 (72.7%) of the 22 patients; the other six (27.3%) cases were found to have recurrent early cancer during the follow-up period from the 36th to the 40th months, and were treated with supplementary endoscopic therapy or surgical resection. It is suggested that endoscopic Nd: YAG laser may be a safe and effective therapy for early carcinoma of the esophagus and the gastric cardia, when the risks of surgery are too high or the patient has refused surgical resection.

Homotransplantation of adrenal gland.

Eight patients with Addison's disease or Cushing's syndrome received adrenal homograft for 9 times after total adrenalectomy. All patients were followed up for 1 to 5 years. Symptoms and signs were improved without the supplement of steroids. The grafts showed satisfactory endocrinal functions in the recipients, but the grafts were dead in two patients 2 and 4 years after operation respectively. One of the two patients received the second homograft with good result. Single perfusion and ice-storage method of the all-adrenal gland and their clinical results were also presented.