Adverse Events of Anti-Tumor Necrosis Factor α Therapy in Ankylosing Spondylitis

Objective

This study aims to investigate the prevalence of short-term and long-term adverse events associated with tumor necrosis factor-α (TNF-α) blocker treatment in Chinese Han patients suffering from ankylosing spondylitis (AS).

Methods

The study included 402 Chinese Han AS patients treated with TNF-α blockers. Baseline data was collected. All patients were monitored for adverse events 2 hours following administration. Long-term treatment was evaluated at 8, 12, 52 and 104 weeks follow-up for 172 patients treated with TNF-α blockers.

Results

Short-term adverse events occurred in 20.15% (81/402), including rash (3.5%; 14/402), pruritus (1.2%; 5/402), nausea (2.2%; 9/402), headache (0.7%; 3/402), skin allergies (4.0%; 16/402), fever (0.5%; 2/402), palpitations (3.0%; 12/402), dyspnea (0.5%; 2/402), chest pain (0.2%; 2/402), abdominal pain (1.0%; 4/402), hypertension (2.2%; 9/402), papilledema (0.5%; 2/402), laryngeal edema (0.2%; 1/402) and premature ventricular contraction (0.2%; 1/402). Long-term adverse events occurred in 59 (34.3%; 59/172) patients, including pneumonia (7.6%; 13/172), urinary tract infections (9.9%; 17/172), otitis media (4.7%; 8/172), tuberculosis (3.5%; 17/172), abscess (1.2%; 2/172), oral candidiasis (0.6%; 1/172), elevation of transaminase (1.7%; 3/172), anemia (1.2%; 2/172), hematuresis (0.6%; 1/172), constipation (2.3%; 4/172), weight loss (0.6%; 1/172), exfoliative dermatitis (0.6%; 1/172). CRP, ESR and disease duration were found to be associated with an increased risk of immediate and long-term adverse events (P<0.05). Long-term treatment with Infliximab was associated with more adverse events than rhTNFR-Fc (P<0.01).

Conclusion

This study reports on the prevalence of adverse events in short-term and long-term treatment with TNF-α blocker monotherapy in Chinese Han AS patients. Duration of disease, erythrocyte sedimentation rate, and c-reactive protein serum levels were found to be associated with increased adverse events with anti-TNF-α therapy. Long-term treatment with Infliximab was associated with more adverse events than rhTNFR-Fc.     

Branchial Cilia and Sperm Flagella Recruit Distinct Axonemal Components

Eukaryotic cilia and flagella have highly conserved 9 + 2 structures. They are functionally diverged to play cell-type-specific roles even in a multicellular organism. Although their structural components are therefore believed to be common, few studies have investigated the molecular diversity of the protein components of the cilia and flagella in a single organism. Here we carried out a proteomic analysis and compared protein components between branchial cilia and sperm flagella in a marine invertebrate chordate, Ciona intestinalis. Distinct feature of protein recruitment in branchial cilia and sperm flagella has been clarified; (1) Isoforms of α- and β-tubulins as well as those of actins are distinctly used in branchial cilia or sperm flagella. (2) Structural components, such as dynein docking complex, tektins and an outer dense fiber protein, are used differently by the cilia and flagella. (3) Sperm flagella are specialized for the cAMP- and Ca²⁺-dependent regulation of outer arm dynein and for energy metabolism by glycolytic enzymes. Our present study clearly demonstrates that flagellar or ciliary proteins are properly recruited according to their function and stability, despite their apparent structural resemblance and conservation.     

Factors Associated with Patient and Provider Delays for Tuberculosis Diagnosis and Treatment in Asia: A Systematic Review and Meta-Analysis

Background

Delays in tuberculosis (TB) diagnosis and treatment is a major barrier to effective management of the disease. Determining the factors associated with patient and provider delay of TB diagnosis and treatment in Asia may contribute to TB prevention and control.

Methods

We searched the PubMed, EMBASE and Web of Science for studies that assessed factors associated with delays in care-seeking, diagnosis, or at the beginning of treatment, which were published from January 1992 to September 2014. Two reviewers independently identified studies that were related to our meta-analysis and extracted data from each study. Independent variables were categorized in separate tables for patient and provider delays.

Results

Among 45 eligible studies, 40 studies assessed patient delay whereas 30 assessed provider delay. Cross-sectional surveys were used in all but two articles, which included 17 countries and regions. Socio-demographic characteristics, TB-related symptoms and medical examination, and conditions of seeking medical care in TB patients were frequently reported. Male patients and long travel time/distance to the first healthcare provider led to both shorter patient delays [odds ratio (OR) (95% confidence intervals, CI) = 0.85 (0.78, 0.92); 1.39 (1.08, 1.78)] and shorter provider delays [OR (95%CI) = 0.96 (0.93, 1.00); 1.68 (1.12, 2.51)]. Unemployment, low income, hemoptysis, and positive sputum smears were consistently associated with patient delay [ORs (95%CI) = 1.18 (1.07, 1.30), 1.23 (1.02, 1.49), 0.64 (0.40, 1.00), 1.77 (1.07, 2.94), respectively]. Additionally, consultation at a public hospital was associated with provider delay [OR (95%CI) = 0.43 (0.20, 0.91)].

Conclusions

We propose that the major opportunities to reduce delays involve enabling socio-demographic factors and medical conditions. Male, unemployed, rural residence, low income, hemoptysis, positive sputum smear, and long travel time/distance significantly correlated with patient delay. Male, long travel time/distance and consultation at a public hospital were related to provider delay.     

不同预处理方法影响昆虫干标本DNA提取效果

为从昆虫干标本中获取高质量DNA,以利于后期PCR扩增目的基因,本研究对DNA提取前昆虫干标本的预处理方法进行探讨,分别测定其纯度和质量,并用不同引物进行了扩增效果对比。结果显示:经过预处理的样品DNA平均含量均高于CK的52.283 ng/滋L,最高为0.9%Na Cl处理3 h,平均含量达122.632 ng/滋L;米象4种预处理方法提取的DNA利用引物Lco1490/Hco2198及UEA7/UEA10均能扩增出650 bp长度条带,仅有0.9%Na Cl溶液浸泡3 h处理的米象可通过引物J173/J1331扩增出1 000 bp的长片段条带。研究表明,经过预处理后,一定程度上减少了基因组DNA的断链,主要对样品DNA的质量浓度影响显著;以9%Na Cl溶液3 h预处理后的昆虫干标本,利用磁珠法所提DNA的质量及PCR扩增效果最佳。     

Deletion of aquaporin-4 in APP/PS1 mice exacerbates brain Aβ accumulation and memory deficits

Background

Preventing or reducing amyloid-beta (Aβ) accumulation in the brain is an important therapeutic strategy for Alzheimer’s disease (AD). Recent studies showed that the water channel aquaporin-4 (AQP4) mediates soluble Aβ clearance from the brain parenchyma along the paravascular pathway. However the direct evidence for roles of AQP4 in the pathophysiology of AD remains absent.

Results

Here, we reported that the deletion of AQP4 exacerbated cognitive deficits of 12-moth old APP/PS1 mice, with increases in Aβ accumulation, cerebral amyloid angiopathy and loss of synaptic protein and brain-derived neurotrophic factor in the hippocampus and cortex. Furthermore, AQP4 deficiency increased atrophy of astrocytes with significant decreases in interleukin-1 beta and nonsignficant decreases in interleukin-6 and tumor necrosis factor-alpha in hippocampal and cerebral samples.

Conclusions

These results suggest that AQP4 attenuates Aβ pathogenesis despite its potentially inflammatory side-effects, thus serving as a promising target for treating AD.

     

多潜能乳腺干细胞的发现

小鼠乳腺由多种不同类型的上皮细胞构成。多潜能干细胞位于乳腺发育的顶端,是乳腺中所有分化细胞类型的来源。然而,这群多潜能乳腺干细胞此前尚未通过特定的标记基因得到鉴定,其存在性也备受争议。借助乳腺干细胞体外培养体系,从Wnt信号通路入手,发现了蛋白C受体基因Procr。在乳腺中,Procr作为一个新的Wnt信号通路的靶基因,能够标记多潜能乳腺干细胞。Procr标记乳腺基底细胞中的一个亚群,这个亚群的细胞低表达基底细胞普遍表达的角蛋白,表现出上皮–间充质转化的特性。Procr阳性的细胞在移植实验中表现出最高的乳腺重建率,体内追踪Procr阳性细胞的后代,发现Procr阳性细胞能够在发育过程中分化形成乳腺上皮的所有细胞类型。多潜能乳腺干细胞的发现结束了乳腺中多潜能干细胞存在性的争议,对乳腺癌的诊断及靶向治疗具有重大意义。     

Joint Analysis of Survival Time and Longitudinal Categorical Outcomes

In biomedical or public health research, it is common for both survival time and longitudinal categorical outcomes to be collected for a subject, along with the subject’s characteristics or risk factors. Investigators are often interested in finding important variables for predicting both survival time and longitudinal outcomes which could be correlated within the same subject. Existing approaches for such joint analyses deal with continuous longitudinal outcomes. New statistical methods need to be developed for categorical longitudinal outcomes. We propose to simultaneously model the survival time with a stratified Cox proportional hazards model and the longitudinal categorical outcomes with a generalized linear mixed model. Random effects are introduced to account for the dependence between survival time and longitudinal outcomes due to unobserved factors. The Expectation–Maximization (EM) algorithm is used to derive the point estimates for the model parameters, and the observed information matrix is adopted to estimate their asymptotic variances. Asymptotic properties for our proposed maximum likelihood estimators are established using the theory of empirical processes. The method is demonstrated to perform well in finite samples via simulation studies. We illustrate our approach with data from the Carolina Head and Neck Cancer Study (CHANCE) and compare the results based on our simultaneous analysis and the separately conducted analyses using the generalized linear mixed model and the Cox proportional hazards model. Our proposed method identifies more predictors than by separate analyses.     

PFTK1 Promotes Gastric Cancer Progression by Regulating Proliferation,Migration and Invasion

PFTK1, also known as PFTAIRE1, CDK14, is a novel member of Cdc2-related serine/threonine protein kinases. Recent studies show that PFTK1 is highly expressed in several malignant tumors such as hepatocellular carcinoma, esophageal cancer, breast cancer, and involved in regulation of cell cycle, tumors proliferation, migration, and invasion that further influence the prognosis of tumors. However, the expression and physiological significance of PFTK1 in gastric cancer remain unclear. In this study, we analyzed the expression and clinical significance of PFTK1 by Western blot in 8 paired fresh gastric cancer tissues, nontumorous gastric mucosal tissues and immunohistochemistry on 161 paraffinembedded slices. High PFTK1 expression was correlated with the tumor grade, lymph node invasion as well as Ki-67. Through Cell Counting Kit (CCK)-8 assay, flow cytometry, colony formation, wound healing and transwell assays, the vitro studies demonstrated that PFTK1 overexpression promoted proliferation, migration and invasion of gastric cancer cells, while PFTK1 knockdown led to the opposite results. Our findings for the first time supported that PFTK1 might play an important role in the regulation of gastric cancer proliferation, migration and would provide a novel promising therapeutic strategy against human gastric cancer.