Combined Cathepsin S and hs-CRP predicting inflammation of Abdominal Aortic Aneurysm

Objectives

Cathepsin S (Cat S) protein expression is increased in human abdominal aortic aneurysm (AAA) lesions and Cat S has been suggested a direct role by promoting inflammatory response partly in experimental AAA. The purpose of this study is to observe the expression of serum Cat S and hs-CRP and its clinical significance in AAA patients.

Design and methods

We collected serum samples from 31 AAA patients and 32 controls. Cat S and hs-CRP levels were measured by a sandwich-type enzyme-linked immunosorbent assay (ELISA) and an enhanced immunoturbidimetric assay respectively. The maximum diameter of the AAA was identified by ultrasonography.

Results

The patients with AAA had higher serum Cat S and hs-CRP levels than the controls (p < 0.05). Furthermore, human serum Cat S levels were strongly correlated with hs-CRP by the nonparametric Spearman correlation tests (B = 0.849, p < 0.05). Based on Pearson's correlation test, human serum Cat S and hs-CRP levels were positively correlated with AAA diameter size (p < 0.05). Cat S was correlated independently with the hs-CRP in all subjects (p < 0.01). After adjustment for the maximum diameter of the abdominal aorta-associated variables, Cat S combined hs-CRP (R² = 0.801) is better than Cat S (R² = 0.740) in predicting the maximum diameter of AAA lesions.

Conclusion

Combined serum Cat S and hs-CRP levels are better in predicting the inflammatory activity of AAA lesions in the clinical setting.     

AngⅡ受体拮抗剂对糖尿病肾病蛋白尿的治疗效果及分析

目的　调查血管紧张素Ⅱ (AngⅡ )受体拮抗剂对糖尿病肾病蛋白尿是否有明确的疗效和对肾功能的保护作用。方法　选 4 7例糖尿病肾病患者进入该前瞻性研究 ,其血糖血压均控制在理想水平。随机分为治疗组 2 4例 ,对照组 2 3例 ,两组降压、降糖等治疗措施相仿 ,而治疗组加用AngⅡ受体拮抗剂厄贝沙坦 0 3g ,每日 1次。 结果　治疗 8周后 ,治疗组尿蛋白为 (1 95± 0 6 5 )g/2 4h ,与治疗前的 (3 14± 1 2 2 ) g/2 4h相比明显下降 (P <0 0 1) ,与对照组的 (3 0 1± 1 2 5 ) g/2 4h比较 ,差异有显著性 (P <0 0 1) ,对照组血肌酐为 (2 2 4 5± 2 5 6 ) μmol/L ,与治疗前的 (175 3± 2 2 8) μmol/L相比明显上升 (P <0 0 1) ,与治疗组的 (115 6± 34 2 ) μmol/L比较 ,存在显著性差异 (P <0 0 1)。结论　AngⅡ受体拮抗剂具有降低糖尿病肾病的尿蛋白量 ,以及保护肾功能的作用。     

肝圆韧带桥式分流联合断流术治疗门静脉高压症

目的评价肝圆韧带桥式分流联合断流术治疗门静脉高压症的临床效果.方法对4例应用肝圆韧带桥式分流联合断流术治疗的门静脉高压症病人的手术情况、手术效果、随访结果进行回顾性分析.结果4例病人中,3例接受了肝圆韧带桥式肠腔分流联合断流术,1例接受肝圆韧带桥式脾肾分流术联合断流术.术中利用肝圆韧带长度4～6 cm,平均5 cm.分流后门静脉压力平均下降7.6 cm H2O,本组无手术死亡及严重手术并发症.随访肝功能均有明显改善,食管胃底静脉曲张均消失,彩超检查肝圆韧带桥无堵塞,吻合口通畅,无再出血.结论肝圆韧带桥式分流联合断流术是一种新的有效的治疗门静脉高压症的手术方式.     

Application of metaphase HR-CGH and targeted Chromosomal Microarray Analyses to genomic characterization of 116 patients with mental retardation and dysmorphic features

Recent advances in molecular cytogenetics enable identification of small chromosomal aberrations that are undetectable by routine chromosome banding in 5-20% of patients with mental retardation/developmental delay (MR/DD) and dysmorphism. The aim of this study was to compare the clinical usefulness of two molecular cytogenetic techniques, metaphase high-resolution comparative genomic hybridization (HR-CGH) and targeted array CGH, also known as Chromosomal Microarray Analysis (CMA). A total of 116 patients with unexplained mild to severe MR and other features suggestive of a chromosomal abnormality with apparently normal or balanced karyotypes were analyzed using HR-CGH (43 patients) and/or CMA (91 patients). Metaphase HR-CGH detected seven interstitial deletions (16.3%). Rare deletions of chromosomes 16 (16p11.2p12.1) and 8 (8q21.11q21.2) were identified. Targeted CMA revealed copy-number changes in 19 of 91 patients (20.8%), among which 11 (11.8%) were clinically relevant, 6 (6.5%) were interpreted as polymorphic variants and 2 (2.1%) were of uncertain significance. The changes varied in size from 0.5 to 12.9 Mb. In summary, our results show that metaphase HR-CGH and array CGH techniques have become important components in cytogenetic diagnostics, particularly for detecting cryptic constitutional chromosome imbalances in patients with MR, in whom the underlying genetic defect is unknown. Additionally, application of both methods together increased the detection rates of genomic imbalances in the tested groups.     

Endothelium-induced proliferation and electrophysiological differentiation of human embryonic stem cell-derived neuronal precursors

Neurogenesis occurs in a stem cell niche in which vascular elements, including endothelial cells (ECs), are thought to play an important role. Using co-culture experiments, we investigated the effect of ECs on proliferation and functional neuronal differentiation of human embryonic stem (ES) cellderived neuronal precursor cells (NPCs). NPCs were cultured for 5 days in medium containing fibroblast growth factor-2 (FGF-2), with or without ECs. FGF-2 and ECs were then removed, and NPCs were maintained in culture for additional periods. Compared to control NPC cultures, EC-treated NPC cultures showed increased cell proliferation at short intervals (5 days) after withdrawal of FGF-2 and larger tetrodotoxin-sensitive inward membrane currents at longer intervals (10-14 days), but a similar pattern of development of neuronal differentiation markers. The effects of ECs appeared to result from the release of soluble factors rather than from cell contact, because they were observed despite the physical separation of NPCs from ECs by a cell-impermeable membrane. These findings indicate that ECs can regulate the proliferation and electrophysiological neuronal differentiation of human NPCs.     

Validation of the Chinese version of the hypomania checklist (HCL-32) as an instrument for detecting hypo(mania) in patients with mood disorders

BACKGROUND: Bipolar disorder (BP) has been consistently under-recognized and erroneously diagnosed as major depression. The resulting inappropriate or delayed treatment is associated with elevated risk of (hypo)mania or cycling. The recognition of (hypo)manic episodes is essential for the correct diagnosis of BP. The Hypomania CheckList (HCL-32) is developed to increase the detection of suspected or manifest but mistreated BP cases. We aimed to determine the accuracy and validity of the Chinese version of the HCL-32 in an adult psychiatric setting. We also compared the results with prior studies carried out in a comparable sample. METHODS: Patients suffering from mood disorders completed the HCL-32 before being interviewed with the Schedule for Affective Disorder and Schizophrenia-Lifetime (SADS-L) to make DSM-IV diagnosis. The 4-day duration criterion for hypomania was replaced by a 2-day cut-off for BPII. The internal consistency and discriminatory capacity of the HCL-32 were analyzed. RESULTS: Results indicated high internal consistency of the Chinese version of the HCL-32. The dual factor structure was confirmed. A score of 14 or more on the HCL-32 total scale distinguished between BP and MDD yielding a sensitivity of 82% and a specificity of 67%. This scale also distinguished between BPI and BPII with a sensitivity of 64% and a specificity of 73% for the cut-off score of 21. LIMITATIONS: The sample size of MDD patients needs to be increased. CONCLUSIONS: The Chinese HCL-32 is a useful screening tool for BP in a psychiatric setting. Its performance is also comparable to that reported in previous studies.     

Interaction analysis of Mycobacterium tuberculosis between the host environment and highly mutated genes from population genetic structure comparison

We aimed to investigate the genetic and demographic differences and interactions between areas where observed genomic variations in Mycobacterium tuberculosis (M. tb) were distributed uniformly in cold and hot spots.The cold and hot spot areas were identified using the reported incidence of TB over the previous 5 years. Whole genome sequencing was performed on 291 M. tb isolates between January and June 2018. Analysis of molecular variance and a multifactor dimensionality reduction (MDR) model was applied to test gene-gene-environment interactions. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were computed to test the extent to which genetic mutation affects the TB epidemic using a multivariate logistic regression model.The percentage of the Beijing family strain in hot spots was significantly higher than that in cold spots (64.63% vs 50.69%, P = .022), among the elderly, people with a low BMI, and those having a history of contact with a TB patient (all P < .05). Individuals from cold spot areas had a higher frequency of out-of-town traveling (P < .05). The mutation of Rv1186c, Rv3900c, Rv1508c, Rv0210, and an Intergenic Region (SNP site: 3847237) showed a significant difference between cold and hot spots. (P < .001). The MDR model displayed a clear negative interaction effect of age groups with BMI (interaction entropy: −3.55%) and mutation of Rv0210 (interaction entropy: −2.39%). Through the mutations of Rv0210 and BMI had a low independent effect (interaction entropy: −1.46%).Our data suggests a statistically significant role of age, BMI and the polymorphisms of Rv0210 genes in the transmission and development of M. tb. The results provide clues for the study of susceptibility genes of M. tb in different populations. The characteristic strains showed a local epidemic. Strengthening genotype monitoring of strains in various regions can be used as an early warning signal of epidemic spillover.     

Disseminated subcutaneous cysticercosis: a report of six cases in Burkina Faso

Cysticercosis is an infection resulting from the larval form of the pig tapeworm, Taenia solium. The subcutaneous localizations are frequent and can have serious consequences such as neurological attacks. We report six cases among whom five men and a woman, in order to point out the severity of the disease and its possible dissemination. The patients' age was ranging from 25 to 57 years old. Three of them had neurological complications as convulsions and headaches. The nodules were painful in one case. We recommend sanitary education to eradicate the affection and to sensitize patients in order to consult physicians at early stage.     

Deletion of TnAbaR23 results in both expected and unexpected antibiogram changes in a multidrug-resistant Acinetobacter baumannii strain

Since the 2006 discovery of the Acinetobacter baumannii strain AYE AbaR1 resistance island, similar elements have been reported in numerous members of this species. As AbaR1 is distantly related to Tn7, we have renamed it TnAbaR1. TnAbaR transposons are known to carry multiple antibiotic resistance- and efflux-associated genes, although none have been experimentally studied en bloc. We deleted the TnAbaR transposon in A. baumannii A424, which we have designated TnAbaR23, and characterized independent deletion mutants DCO163 and DCO174. The NotI pulsed-field gel electrophoresis (PFGE) profile of strain DCO174 was consistent with targeted deletion of TnAbaR23 alone, but strain DCO163 apparently harbored a second large genomic deletion. Nevertheless, "subtractive amplification" targeting 52 TnAbaR and/or resistance-associated loci yielded identical results for both mutants and highlighted genes lost relative to strain A424. PCR mapping and genome sequencing revealed the entire 48.3-kb sequence of TnAbaR23. Consistent with TnAbaR23 carrying two copies of sul1, both mutants exhibited markedly increased susceptibility to sulfamethoxazole. In contrast, loss of tetAR(A) resulted in only a minor and variable increase in tetracycline susceptibility. Despite not exhibiting a growth handicap, strain DCO163 was more susceptible than strain DCO174 to 9 of 10 antibiotics associated with mutant-to-mutant variation in susceptibility, suggesting impairment of an undefined resistance-associated function. Remarkably, despite all three strains sharing identical gyrA and parC sequences, the ciprofloxacin MIC of DCO174 was >8-fold that of DCO163 and A424, suggesting a possible paradoxical role for TnAbaR23 in promoting sensitivity to ciprofloxacin. This study highlights the importance of experimental scrutiny and challenges the assumption that resistance phenotypes can reliably be predicted from genotypes alone.     

Pharmacokinetic/Pharmacodynamic predictors of clinical potency for hepatitis C virus nonnucleoside polymerase and protease inhibitors

This analysis was conducted to determine whether the hepatitis C virus (HCV) viral kinetics (VK) model can predict viral load (VL) decreases for nonnucleoside polymerase inhibitors (NNPolIs) and protease inhibitors (PIs) after 3-day monotherapy studies of patients infected with genotype 1 chronic HCV. This analysis includes data for 8 NNPolIs and 14 PIs, including VL decreases from 3-day monotherapy, total plasma trough concentrations on day 3 (C(min)), replicon data (50% effective concentration [EC(50)] and protein-shifted EC(50) [EC(50,PS)]), and for PIs, liver-to-plasma ratios (LPRs) measured in vivo in preclinical species. VK model simulations suggested that achieving additional log(10) VL decreases greater than one required 10-fold increases in the C(min). NNPolI and PI data further supported this result. The VK model was successfully used to predict VL decreases in 3-day monotherapy for NNPolIs based on the EC(50,PS) and the day 3 C(min). For PIs, however, predicting VL decreases using the same model and the EC(50,PS) and day 3 C(min) was not successful; a model including LPR values and the EC(50) instead of the EC(50,PS) provided a better prediction of VL decrease. These results are useful for designing phase 1 monotherapy studies for NNPolIs and PIs by clarifying factors driving VL decreases, such as the day 3 C(min) and the EC(50,PS) for NNPolIs or the EC(50) and LPR for PIs. This work provides a framework for understanding the pharmacokinetic/pharmacodynamic relationship for other HCV drug classes. The availability of mechanistic data on processes driving the target concentration, such as liver uptake transporters, should help to improve the predictive power of the approach.