Sensory evoked potentials in patients with Rett syndrome through the lens of animal studies: Systematic review

ObjectiveSystematically review the abnormalities in event related potential (ERP) recorded in Rett Syndrome (RTT) patients and animals in search of translational biomarkers of deficits related to the particular neurophysiological processes of known genetic origin (MECP2 mutations).MethodsPubmed, ISI Web of Knowledge and BIORXIV were searched for the relevant articles according to PRISMA standards.ResultsERP components are generally delayed across all sensory modalities both in RTT patients and its animal model, while findings on ERPs amplitude strongly depend on stimulus properties and presentation rate. Studies on RTT animal models uncovered the abnormalities in the excitatory and inhibitory transmission as critical mechanisms underlying the ERPs changes, but showed that even similar ERP alterations in auditory and visual domains have a diverse neural basis. A range of novel approaches has been developed in animal studies bringing along the meaningful neurophysiological interpretation of ERP measures in RTT patients.ConclusionsWhile there is a clear evidence for sensory ERPs abnormalities in RTT, to further advance the field there is a need in a large-scale ERP studies with the functionally-relevant experimental paradigms.SignificanceThe review provides insights into domain-specific neural basis of the ERP abnormalities and promotes clinical application of the ERP measures as the non-invasive functional biomarkers of RTT pathophysiology.     

Matrix metalloproteinase 9 (MMP9) level and MMP9 -1562C>T in patients with obstructive sleep apnea: a systematic review and meta-analysis of case-control studies

BackgroundThe peripheral level of matrix metalloproteinase (MMP)-9 and polymorphism of MMP9 -1562C>T in patients with obstructive sleep apnea (OSA) remains controversial. Therefore, the aims of this systemic review and meta-analysis are to assess the MMP9 level in OSA patients and identify the relationship between MMP9 -1562C>T and OSA susceptibility.MethodsThis systematic review was performed following the PRISMA guideline. We searched for studies in major databases, identifying those indexed from inception to July 3, 2019 which related to MMP9 level, MMP9 -1562C>T and OSA. The pooled standardized mean differences (SMDs) and 95% confidence interval (CI) of MMP9 levels were calculated. In addition, the relationship between MMP9 -1562C>T and OSA susceptibility was assessed by three genetic models. The heterogeneity analysis and calculation of the pooled odds ratio (OR) were also performed, followed by quality assessment using the Newcastle-Ottawa Scale (NOS).ResultsIn sum, our review included 15 eligible studies regarding MMP9 level and three regarding MMP9 -1562C>T. The pooled results showed that peripheral level of MMP9 was increased in OSA patients (SMD = 1.37; 95% CI = 1.15–1.59). Furthermore, significant difference of MMP9 level can be found between severe and mild-to-moderate OSA patients (SMD = 28.17; 95% CI = 4.23–52.11) or between moderate-severe and mild OSA (SMD = 36.62; 95% CI = 12.19–61.04). However, no relationship was observed between MMP9 -1562C>T and OSA susceptibility in three genetic models (Homozygote model, OR = 1.37; 95% CI = 0.87–2.18); (Recessive model, OR = 1.42; 95% CI = 0.83–2.42); (Allele model, OR = 1.07; 95% CI = 0.96–1.18).ConclusionsThis systemic review and meta-analysis indicated that the level of MMP9 was increased in patients with OSA and this increase is relevant to OSA severity. Moreover, the relationship between MMP9 -1562 C>T and OSA susceptibility has currently not been proven by current merging values. Further analyses with larger sample size are required to verify these associations.     

Peak C-reactive protein levels do not predict 30-day mortality for bacteremia: A retrospective cohort study

IntroductionAlthough peak C-reactive protein (CRP) levels are correlated with the prognosis of some diseases, there have been no reports regarding the association between peak CRP levels and mortality in patients with bacteremia. The present study aimed to determine the association between peak CRP levels and prognosis in patients with bacteremia.MethodsThis retrospective cohort study was conducted in a single tertiary hospital and included patients with bacteremia admitted to the emergency department from November 2012 to March 2017. Cox regression analysis was performed to examine the association between peak CRP levels and 30-day mortality. We also performed propensity score adjustment using potential confounding factors.ResultsOne hundred fifty-nine patients were included in the study. Peak CRP levels were significantly higher in the β-hemolytic streptococci (P = 0.001) and Streptococcus pneumoniae (P = 0.003) groups. The C-statistic of the multivariate logistic regression model for the propensity score was 0.88. For 30-day mortality, peak CRP levels >20 mg/dL did not show significance in the Cox regression analysis (hazard ratio, 0.866; 95% confidence interval, 0.489–1.537; P = 0.62). Even after propensity score adjustment, no significance was noted (hazard ratio, 0.865; 95% confidence interval, 0.399–1.876; P = 0.71).ConclusionsPeak CRP levels were not an independent predictor of mortality in patients with bacteremia in the emergency department. Clinicians should consider that patients with extremely high peak CRP levels do not necessarily have high mortality and vice versa.     

Emodin attenuates acute lung injury in Cecal-ligation and puncture rats

Acute lung injury (ALI) is a major cause of sepsis-induced acute respiratory failure. Emodin has been considered to play a protective role for acute lung edema in cecal ligation and puncture (CLP)-induced sepsis model. In this study we aimed to investigate whether emodin could improve CLP-induced lung sepsis via regulating aquaporin (AQP) and tight junction (TJ), inflammatory factors, and pulmonary apoptosis. The results showed that sepsis-induced pulmonary pathological changes were significantly improved after emodin treatment. Emodin was found to upregulate AQP and TJ expression in the CLP model. Meanwhile, inflammatory cytokine release and pulmonary apoptosis was remarkably reduced after emodin treatment in lung sepsis. Our data demonstrated that emodin could suppresse inflammation, restore pulmonary epithelial barrier and reduce mortality in CLP-induced ALI, suggesting the potential therapeutic application of emodin in sepsis.     

Inactivated influenza vaccine formulated with single-stranded RNA-based adjuvant confers mucosal immunity and cross-protection against influenza virus infection

Influenza vaccination is considered the most valuable means to prevent and control seasonal influenza infections, which causes various clinical symptoms, ranging from mild cough and fever to even death. Among various influenza vaccine types, the inactivated subunit type is known to provide improved safety with reduced reactogenicity. However, there are some drawbacks associated with inactivated subunit type vaccines, with the main ones being its low immunogenicity and the induction of Th2-biased immune responses. In this study, we investigated the role of a single-stranded RNA (ssRNA) derived from the intergenic region in the internal ribosome entry site of the Cricket paralysis virus as an adjuvant rather than the universal vaccine for a seasonal inactivated subunit influenza vaccine. The ssRNA adjuvant stimulated not only well-balanced cellular (indicated by IgG2a, IFN-γ, IL-2, and TNF-α) and humoral (indicated by IgG1 and IL-4) immune responses but also a mucosal immune response (indicated by IgA), a key protector against respiratory virus infections. It also increases the HI titer, the surrogate marker of influenza vaccine efficacy. Furthermore, ssRNA adjuvant confers cross-protective immune responses against heterologous influenza virus infection while promoting enhanced viral clearance. Moreover, ssRNA adjuvant increases the number of memory CD4⁺ and CD8⁺ T cells, which can be expected to induce long-term immune responses. Therefore, this ssRNA-adjuvanted seasonal inactivated subunit influenza vaccine might be the best influenza vaccine generating robust humoral and cellular immune responses and conferring cross-protective and long-term immunity.     

免疫检查点抑制剂治疗少见突变非小细胞肺癌疗效的研究进展

驱动基因的发现及针对驱动基因的靶向治疗已显著提高了肺癌患者的生存质量和时间，但目前对于BRAF、HER2、MET、RET等少见驱动基因改变肺癌患者的靶向药物的选择仍然较少。近年来免疫检查点抑制剂在肺癌治疗中取得了一定的疗效，但因为少见驱动基因突变的肺癌患者本身样本量少，开展大规模临床随机对照试验尚存在一定的困难，目前此类患者接受免疫检查点抑制剂治疗的疗效情况仍不明确。本文将对目前已掌握的免疫检查点抑制剂治疗BRAF、HER2、MET、RET等少见驱动基因改变肺癌患者的临床研究结果进行综述，以期在一定程度上为临床工作提供一些依据和参考。     

The effects of grass pollen allergoid immunotherapy on clinical and immunological parameters in children with allergic rhinitis

Allergoid immunotherapy is a new form of allergen immunotherapy allowing safe administration of high allergen doses. There is limited information on the effects of allergoid immunotherapy in children with allergic rhinitis. To investigate the immunological and clinical effects of allergoid immunotherapy in children with allergic rhinitis due to grass pollen allergy. Children with allergic rhinitis were assigned to allergoid immunotherapy (n = 27) or control (n = 26, no immunotherapy) groups. Children in the immunotherapy group received seven injections of grass pollen allergoid immunotherapy before grass pollen season and continued to receive maintenance immunotherapy for 27 months. All patients were offered a pharmacotherapy regimen to be used on demand during the pollen seasons. Clinical and laboratory parameters were compared between the immunotherapy and control groups. The rhinoconjunctivitis symptom-medication score and asthma symptom score were lower in the immunotherapy group after 1 yr of maintenance immunotherapy (p < 0.01 for both). Skin test reactivity and nasal reactivity as determined by nasal provocation testing for grass pollen were significantly decreased after 1 yr of immunotherapy (p < 0.001 for both). The seasonal increase in bronchial reactivity and nasal lavage eosinophil cationic protein levels were prevented after the first year of immunotherapy (p < 0.05 for both). The seasonal increase in immunoglobulin (Ig)E decreased (p < 0.05) and grass-specific IgG, IgG(1) and IgG(4) increased significantly already at the end of the seven-injection build-up therapy (p < 0.001, for all). Interleukin (IL)-4 levels in the culture supernatants showed a steady decline from baseline at first and second year of immunotherapy (p < 0.001) but remained unchanged in the control group. Allergoid immunotherapy is an effective method in the treatment of grass pollen-induced allergic rhinitis in children and prevents the seasonal increase in bronchial hyper-reactivity. Changes in specific IgE and IgG levels and decreased IL-4 production in peripheral blood mononuclear cell culture supernatants may account for the observed clinical effects.     

CORRELATIONS BETWEEN VIDEO CAPSULE ENDOSCOPIC FINDINGS AND CLINICAL ACTIVITY IN CROHN’S DISEASE

Background and Aims: Video capsule endoscopy (VCE) has become increasingly important as a simple method for observing the entire small intestine. The indications for VCE are obscure gastrointestinal bleeding and investigation of Crohn’s disease (CD). However, the correlation between endoscopic findings obtained by VCE and clinical findings in known cases of CD is not clear, and we therefore investigated this in the present study. Patients and methods: In 30 patients with known CD (Crohn’s disease activity index [CDAI] 0–420; median = 158.3), double contrast enteroclysis (ENT) was performed 1–3 weeks prior to VCE. The relationship between the VCE findings and hematological analysis/CDAI was examined. Results: In 17 of 30 patients, the entire small intestine could be investigated by VCE, whereas in the remaining 13 patients the terminal ileum could not be investigated. The following exhibited positive correlations: total lesions and CDAI (correlation coefficient values: r_s = 0.661, adjusted P < 0.0061), ulcers and C‐reactive protein (CRP) (r_s = 0.607, adjusted P < 0.0061), total lesions and CRP (r_s = 0.604, adjusted P < 0.0061). Conclusions: Analysis with VCE suggests that CDAI and CRP indicate the activity of intestinal lesions in patients with known CD, and that CRP, in particular, is associated with the activity of ulcerative lesions of the intestine. This may contribute to revised guidelines for VCE in the future.     

谷氨酰胺转移酶对大豆分离蛋白成膜性能的影响

研究了谷氨酰胺转移酶（TGase）对大豆蛋白膜特性的影响。研究表明：在成膜溶液中加入TGase（4U／g）可以使膜的抗拉强度增加16．79，6，表面疏水性增加39．2％，同时也明显降低了膜的断裂伸长率、水分含量、总可溶性物质量及透光率，但是对水蒸气转移速率几无影响。扫描电镜（SEM）显示，酶法交联膜的表面比对照膜略为粗糙，断面却更为均匀致密。SDS-PAGE分析表明，TGase催化SPI产生了共价交联。