Effects of Mineralocorticoid Receptor Antagonists for Chronic Kidney Disease: A Systemic Review and Meta-Analysis.

BACKGROUND: Mineralocorticoid receptor blockade could be a potential approach for the inhibition of chronic kidney disease (CKD) progression. The benefits and harms of different mineralocorticoid receptor antagonists (MRAs) in CKD are inconsistent. OBJECTIVES: The aim of the study was to summarize the benefits and harms of MRAs for CKD patients. METHODS: We searched MEDLINE, EMBASE, and the Cochrane databases for trials assessing the effects of MRAs on non-dialysis-dependent CKD populations. Treatment and adverse effects were summarized using meta-analysis. RESULTS: Fifty-three trials with 6 different MRAs involving 22,792 participants were included. Compared with the control group, MRAs reduced urinary albumin-to-creatinine ratio (weighted mean difference [WMD], -90.90 mg/g, 95% CI, -140.17 to -41.64 mg/g), 24-h urinary protein excretion (WMD, -0.20 g, 95% CI, -0.28 to -0.12 g), estimated glomerular filtration rate (eGFR) (WMD, -1.99 mL/min/1.73 m2, 95% CI, -3.28 to -0.70 mL/min/1.73 m2), chronic renal failure events (RR, 0.86, 95% CI, 0.79-0.93), and cardiovascular events (RR, 0.84, 95% CI, 0.77-0.92). MRAs increased the incidence of hyperkalemia (RR, 2.04, 95% CI, 1.73-2.40) and hypotension (RR, 1.80, 95% CI, 1.41-2.31). MRAs reduced the incidence of peripheral edema (RR, 0.65, 95% CI, 0.56-0.75) but not the risk of acute kidney injury (RR, 0.94, 95% CI, 0.79-1.13). Nonsteroidal MRAs (RR, 0.66, 95% CI, 0.57-0.75) but not steroidal MRAs (RR, 0.20, 95% CI, 0.02-1.68) significantly reduced the risk of peripheral edema. Steroidal MRAs (RR, 5.68, 95% CI, 1.26-25.67) but not nonsteroidal MRAs (RR, 0.52, 95% CI, 0.22-1.22) increased the risk of breast disorders. CONCLUSIONS: In the CKD patients, MRAs, particularly in combination with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, reduced albuminuria/proteinuria, eGFR, and the incidence of chronic renal failure, cardiovascular and peripheral edema events, whereas increasing the incidence of hyperkalemia and hypotension, without the augment of acute kidney injury events. Nonsteroidal MRAs were superior in the reduction of more albuminuria with fewer peripheral edema events and without the augment of breast disorder events.

Aspirin intervention before ICU admission reduced the mortality in critically ill patients with acute kidney injury: results from the MIMIC-IV.

Background: Aspirin, with its pleiotropic effects such as anti-inflammatory and anti-platelet aggregation, has been widely used for anti-inflammatory, analgesic, and cardiovascular diseases. However, the association between the use of aspirin before the intensive care unit (ICU) and clinical outcomes in critically ill patients with acute kidney injury (AKI) is unknown. Methods: Patients with AKI in this retrospective observational study were selected from the Marketplace for Medical Information in Intensive Care IV (MIMIC-IV). The association between aspirin intervention and 30-day mortality was assessed using Cox proportional hazards model. Logistic regression models were used to assess the association of aspirin intervention with the risks of intracranial hemorrhage, gastrointestinal bleeding and blood transfusion. The propensity score matching (PSM) method was adopted to balance the baseline variables. Sensitivity analysis was performed to validate the results by multiple interpolations for the missing data. Results: The study included 4237 pre-ICU aspirin users and 9745 non-users. In multivariate models, we found a decreased risk of mortality in those who received aspirin before ICU compared to those who did not (30-day:hazard ratio [HR], 0.70; 95% CI, 0.62-0.79; p < 0.001; 90-day:HR, 0.70; 95% CI, 0.63-0.77, p < 0.001; 180-day:HR, 0.72; 95%CI,0.65-0.79, p < 0.001). This benefit was consistent in the post-PSM analyses, sensitivity analyses, and subgroup analyses. Moreover, aspirin intervention was associated with a reduced risk of intracranial hemorrhage and gastrointestinal bleeding (HR, 0.16; 95% CI, 0.10-0.25; p < 0.001; HR, 0.59; 95% CI, 0.38-0.88, p = 0.012) after being adjusted by relating covariates, whereas with a increased risk of blood transfusion (HR, 1.28; 95% CI, 1.16-1.46; p < 0.001). Conclusion: Patients with AKI treated with aspirin before ICU admission might have reduced 30-day, 90-day and 180-day mortality without increasing the risk of intracranial hemorrhage (ICH) or gastrointestinal bleeding, but may increase the risk of transfusion.

Immune responses of mice inoculated with recombinant Lactobacillus plantarum NC8 expressing the fusion gene HA2 and 3M2e of the influenza virus and protection against different subtypes of influenza virus.

To evaluate the efficiency of preventing pathogenic avian influenza by vaccination with recombinant Lactobacillus plantarum (L. plantarum) that expresses conserved antigens, the mucosal and systemic immune responses in animals vaccinated with recombinant L. plantarum NC8-409-1 (NC8-pSIP409-pgsA'-HA2) and NC8-409-2 (NC8-pSIP409-pgsA'-3M2e-HA2) were evaluated. Our results showed that recombinant L. plantarum NC8-409-1 and NC8-409-2 could substantially stimulate the specific IgA titer in the intestine and the specific IgG antibody titer in the serum. We also found that recombinant L. plantarum induced increases in the number of B220+ IgA+ cells in Peyer's patches (PPs), in lymphocyte proliferation and in the number of IFN-γ+ producing CD8+ T cells after immunization in mice. Most importantly, the mice that were vaccinated with recombinant L. plantarum NC8-409-2 and NC8-409-1 were to some extent protected against infection challenge with the H9N2 and H1N1 viruses. In particular, NC8-409-2 provided up to 80% protection against the H9N2 virus, and NC8-409-1 provided up to 60% protection. Lung tissue pathology was also reduced. Therefore, recombinant L. plantarum NC8-409-2 and NC8-409-1 may be candidate oral vaccines against bird flu.

[Application of micro-lecture in standardized training of endodontic residents].

PURPOSE: To apply micro-lecture in standardized training of endodontic residents, in order to improve training quality. METHODS: Twenty endodontic residents were randomly divided into 2 groups, 10 students in each group. One group were taught with micro-lecture while the other group with lecture-based learning (LBL). The teaching effect was measured with examination and questionnaire survey. The examination results were analyzed by Student's t test using SPSS 18.0 software package. RESULTS: Micro-lecture group was better than LBL group in practical test and total scores, there were significant differences between the two groups (P＜0.05). Micro-lecture group was better than LBL group in didactic test, but there was no significant difference between the two groups (P＞0.05). Questionnaire survey showed that micro-lecture was well accepted by residents for its novelty and flexibility, self-motivated learning ability was trained, communication between teachers and residents was enhanced, but the production level of micro-lecture video needs to be improved. CONCLUSIONS: Micro-lecture achieves satisfactory teaching effect, and can be applied in standardized training of endodontic residents.

[Effects of Porphyromonas endodontalis lipopolysaccharides on the expression of monocyte chemotactic protein-1 in mouse osteoblasts].

PURPOSE: To investigate the effects of lipopolysaccharide (LPS) extracted from Porphyromonas endodontalis (P.endodontalis) on expression of monocyte chemotactic protein-1 (MCP-1) mRNA and protein in MC3T3-E1 cells and the role of p38 mitogen-activated　protein　kinase (MAPK) and nuclear factor-kB(NF-kB）in the process. METHODS: MC3T3-E1 cells were treated with different concentrations of P.endodontalis LPS(0-50mg/L) and 20 mg/L P.endodontalis LPS for different hours (0-48 h). The expression of MCP-1 mRNA was detected by real-time reverse transcription PCR(RT-PCR) and protein was detected by enzyme-1inked immunosorbent assay (ELISA). MC3T3-E1 cells were pretreated with SB203580 (inhibitor of p38MAPK) and BAY11-7082 (inhibitor of NF-kB) for 1h, and then were treated with 20 mg/L P.endodontalis LPS for 24 h, the expression of MCP-1 mRNA was also detected by RT-PCR. Statistical analysis was performed using one-way ANOVA and Dunnett t test with SPSS 13.0 software package. RESULTS: The level of MCP-1 mRNA and protein increased significantly after treatment with different concentrations of P.endodontalis LPS (0-50 mg/L), which indicated that P.endodontalis LPS induced osteoblasts to express MCP-1 in a dose dependent manners. During the observation time (0-48 h), the impact of 20 mg/L P.endodontalis LPS on induction of MCP-1 in MC3T3-E1 cells exhibited a time-dependent manner. The expression of MCP-1 mRNA decreased significantly after pretreated with 10 mol/L SB203580 and BAY11-7082 for 1 h,and the inhibitory effect of SB203580 was stronger than BAY11-7082. CONCLUSIONS: P.endodontalis LPS may induce the expression of MCP-1 mRNA and protein in MC3T3-E1 cells through the signaling pathway of p38MAPK and NF-kB.

[Application of PBL combined with SP method in during-course practice of endodontics for undergraduate dental students].

PURPOSE: To apply problem-based learning (PBL) combined with standardized patients(SP) in during-course practice of endodontics for undergraduate dental students, in order to improve the teaching quality. METHODS: One hundred and four undergraduate dental students of China Medical University School of Stomatology were randomly divided into 2 groups, 52 students in each group. One group were taught with PBL combined with SP while the other group with lecture-based learning (LBL) alone. The teaching effect was measured with examination and questionnaire survey. The data were analyzed by Student's t test using SPSS 11.5 software package. RESULTS: Students in PBL combined with SP group was better than LBL group in case analysis, didactic tests, practical tests and total scores, and there was significant difference between the two groups (P<0.05). LBL group was better than PBL combined with SP group in basic theoretical knowledge scores, and there was significant difference between the two groups (P<0.05). SP and PBL combined with SP method were welcomed by undergraduate dental students. CONCLUSIONS: The abilities of undergraduate dental students can be improved by PBL combined with SP in different aspects. PBL combined with SP achieves satisfactory teaching effect, and can be applied in during-course practice of endodontics to undergraduate dental students.

[Application of problem-based learning in pre-job training of postgraduate students in department of endodontics].

PURPOSE: To apply problem-based learning (PBL) in pre-job training of postgraduate students in department of endodontics. METHODS: Thirty master degree postgraduate students of China Medical University were randomly divided into 2 groups, there were 15 students in each group. One group were taught with PBL method while the other group with lecture-based learning (LBL) method. The teaching effect was measured with examination and questionnaire survey. The data were analyzed by student's t-test using SPSS 11.5 software package. RESULTS: There was no significant difference in basic knowledge, medical records writing, oral examination between the two groups (P>0.05). There were significant differences in case analysis, dental operation, theory examination, practical examination and total scores between the two groups (P<0.05). The PBL method was welcomed by master degree postgraduate students. CONCLUSIONS: The abilities of postgraduate students can be developed by PBL method in different aspects. PBL achieves satisfactory teaching effect, and can be applied in pre-job training of postgraduate students.

[Effect of Carisolv on endodontic microleakage].

PURPOSE: To evaluate the effect of Carisolv on endodontic microleakage by establishing a fluid transport model using sodium nitrite as tracer. METHODS: Seventy extracted teeth were randomly divided into 5 groups, all the root canals were prepared with different chemical reagents, including Carisolv,3% hydrogen peroxide+ 2%tosylchloramide sodium,2.5% sodium hypochlorite,5% sodium hypochlorite(negative control)and distilled water(positive control),post spaces were prepared after cold lateral condensation, the samples were put on the model, concentration of sodium nitrite which penetrated from the coronal to the apical end was measured by diazo reaction at 1,2,4,7,10,15,20,25,30,35,40,45,50,55 and 60 day. The data were analyzed by ANOVA using SPSS 11.5 software package. RESULTS: Sodium nitrite was not detected in negative control group from 1 day to 60 days. High concentration of sodium nitrite was detected in positive control group at first day, concentration of sodium nitrite was higher than that of other four groups from 1day to 60 days(P<0.01). Concentration of sodium nitrite in Carisolv group was significantly lower than that of 3%hydrogen peroxide+ 2% tosylchloramide sodium group(P<0.01), also lower than that of 2.5% sodium hypochlorite group(P<0.05),except at 25,30,35 and 40 days. CONCLUSIONS: Carisolv can remove the smear layer, decrease the endodontic microleakage, seal the root canal better. The fluid transport model using sodium nitrite as tracer can be used to evaluate the endodontic microleakage objectively,sensitively and exactly.

[Hypomethylation of 5'CpG island of insulin-like growth factor binding protein-related protein 1 is associated with its overexpression in colorectal cancer].

OBJECTIVE: To investigate the methylation status of 5'CpG island of insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) in colorectal cancer and its relationship with gene expression and clinicopathologic parameters. METHODS: Semi-quantitative reverse transcription-PCR (RT-PCR) was used to detect the expression of IGFBP-rP1 in 46 cases of colorectal cancer and their matched normal mucosa. Methylation-specific PCR (MSP) was applied to evaluate the methylation status of 5'CpG island of IGFBP-rP1. Colon cancer cell lines LoVo and SW620 were treated with demethylation agent 5-aza-2'-deoxycytidine (5-aza-dC), followed by RT-PCR and MSP detection. RESULTS: At the mRNA level, the expression of IGFBP-rP1 was higher in colorectal cancer tissue than that in the matched normal mucosa (P < 0.05). IGFBP-rP1 was methylated in 28/46 (60.9%) cases of colorectal cancer and 37/46 (80.4%) matched normal mucosa samples (P < 0.05). A negative correlation was found between IGFBP-rP1 expression and its methylation status. The expression of IGFBP-rP1 was restored in LoVo and SW620 after treatment with 5-aza-dC and MSP confirmation of its demethylation status. No relationships was found between the methylation status and clinicopathologic parameters. CONCLUSIONS: IGFBP-rP1 expression is negatively correlated with its methylation status in colorectal cancer. DNA methylation is one of the mechanisms regulating the expression of IGFBP-rP1. Hypomethylation of IGFBP-rP1 gene with its overexpression plays an important role in the initiation and development of colorectal cancer.

[Effect of Carisolv on root canal cleanness in chemomechanical preparation].

PURPOSE: To evaluate the effect of Carisolv as chemical reagent on root canal cleanness in chemomechanical preparation. METHODS: Sixty extracted teeth which were dyed with methylene blue were randomly divided into 3 groups, different chemical reagents were applied in different groups. The optical density of methylene blue in irrigating solution were measured with UV-VIS spectrophotomer after preparation with each file, the root canal cleanness was evaluated under SEM. Two-way ANOVA and Kruskal-Wallis H test in SPSS 11.5 software package were used for statistical analysis. RESULTS: There were significant differences in the optical density between the root canals treated with Carisolv and those with 2% tosylchloramide sodium plus 3% hydrogen peroxide (P<0.05), no significant difference was found in optical density between the root canals treated with Carisolv and those with 2.5% sodium hypochlorite (P>0.05). The results of SEM were consistent with those of the optical density of methylene blue. CONCLUSIONS: As a chemical reagent, the cleaning ability of Carisolv was as effective as 2.5% sodium hypochlorite. Carisolv can remove the smear layer and debris, without causing excessive demineralization. Supported by Key Research Project of Science and Technology Committee of Liaoning Province(Grant No.00225001).

[Study of the relative factors of cure depths of light curing composite resin].

PURPOSE: To investigate the effect of different composite resin, different light curing units, different irradiation time, different irradiation distance on cure depths of light curing composite resin. METHODS: Designed by factorial experiment, 192 Cylindrical samples were made with 4mm internal diameter and 6mm high mold. The whole samples were scanned by Planmeca ProMax panoramic X-ray unit, cure depths were measured using a scoping method described in the ISO standard for resin-based composites. The data was statistically analyzed by SPSS11.5 software package for ANOVA. RESULTS: The differences of four factors-composite resin, light curing units, irradiation time, irradiation distance were significant (P<0.01), and the effects between-subjects were involved among four factors (P<0.01). CONCLUSIONS: From this study, we conclude that cure depths may be affected by two kinds of light curing units, two kinds of composite resin, four kinds of irradiation time and four kinds of irradiation distances, once each factor is strengthened, cure depths could reach a more ideal effect. Supported by Key Research Project of Science and Technology Committee of Liaoning Province (Grant No.00225001).

[The expression of Staufen gene in colorectal cancer].

To study the expression of differential methylation-associated Staufen gene in colorectal cancer (CRC), we detected the expression of Staufen gene in adenocarcinoma, mucosa adjacent to colorectal cancer (MACC) and corresponding distant normal tissue using RT-PCR and immunohistochemistry. We found that the expression of Staufen gene in MACC and adenocarcinoma of CRC was significantly lower than that in corresponding distal normal tissue at mRNA level (P<0.05.No significant associations were found between age, sex, location of cancer (colon/rectal), degree of differentiation and metastasis of lymph node with expression of Staufen gene. Lower expression of Staufen protein in MACC was verified by comparing with matched normal tissue and adenocarcinoma (P<0.05). This study indicated low expression of Staufen gene in colorectal cancer and the Staufen gene might be involved in the development of colorectal cancer.

[Study of B2 gene structure and its expression in colorectal cancer].

OBJECTIVE: To get a complete cDNA sequence of B2 and evaluate the correlation on structure and expression between B2 and insulin like growth factor binding protein related protein 1 (IGFBP-rP1) in colorectal carcinomas, paired normal tissues, adenomas, tissues adjacent to the tumor, and colorectal carcinoma cell lines. METHODS: 5'RACE (rapid amplification of cDNA end) was applied to get the sequence of the 5' end of B2. Semi-quantitative RT-PCR and immunohistochemistry were used to detect the expression of B2 in colorectal cancer tissues and cell lines (SW480, SW1116, SW620, HCT8, CoLo205 and LoVo). RESULTS: A sequence of 1,125 bp was obtained by combining the sequence from 5'RACE product and the known sequence of B2. It shared 1,122/1,125 identities with IGFBP-rP1. At the level of mRNA, the expression of B2/IGFBP-rP1 was high in colorectal carcinomas, moderate in adenomas and tissues adjacent to tumor, low in normal tissues (P < 0.05). Five cell lines except SW480 showed no expression of B2/IGFBP-rP1. A significant difference was obtained in the immunoreactivity of B2/IGFBP-rP1 between normal tissue and cancer (P < 0.05). In 28.9% (22/76) samples, cancer cells locating at the invasive front of cancer nest had a stronger staining of B2/IGFBP-rP1 than those surrounding the lumen. These samples had also an increased frequency of lymph node metastases, increased depth of invasion and a stronger staining of B2/IGFBP-rP1 than in other samples (P < 0.05). CONCLUSIONS: B2 is the same gene as IGFBP-rP1. Overexpression of B2/IGFBP-rP1 may play an important role in the initiation and promotion of colorectal cancer. Its overexpression in invading tumor cells may be linking with an increased potential of invasion.