Factors Associated with Pneumocystis jirovecii Pneumonia in Patients with Rheumatoid Arthritis Receiving Methotrexate: A Single-center Retrospective Study

Objective To investigate the risk factors for the development of Pneumocystis jirovecii pneumonia (PCP) in patients with rheumatoid arthritis (RA) undergoing methotrexate (MTX) therapy. Methods This single-center retrospective cohort study included consecutive patients with RA who received MTX for at least one year. The study population was divided into PCP and non-PCP groups, depending on the development of PCP, and their characteristics were compared. We excluded patients who received biologic disease-modifying anti-rheumatic drugs (DMARDs), Janus kinase inhibitors, and anti-PCP drugs for prophylaxis. Results Thirteen patients developed PCP, and 333 did not develop PCP. At the initiation of MTX therapy, the PCP group had lower serum albumin levels, a higher frequency of pulmonary disease and administration of DMARDs, and received a higher dosage of prednisolone (PSL) than the non-PCP group. A multivariate Cox regression analysis revealed that the concomitant use of PSL [hazard ratio (HR) 5.50, p=0.003], other DMARDs (HR 5.98, p=0.002), and serum albumin <3.5 mg/dL (HR 4.30, p=0.01) were risk factors for the development of PCP during MTX therapy. Patients with these risk factors had a significantly higher cumulative probability of developing PCP than patients who lacked these risk factors. Conclusion Clinicians should pay close attention to patients with RA who possess risk factors for the development of PCP during MTX therapy.     

不同药物与消毒剂对免球虫卵囊孢子化的影响

目的 对比研究不同抗兔球虫药物与消毒剂对兔球虫卵囊孢子化过程的抑杀效果,为兔球虫病的防治提供参考.方法 分别选取5种抗球虫药物和消毒剂进行抑制试验,观察它们对兔球虫卵囊体外孢子化过程的影响.结果 (1)5种抗球虫药物对兔球虫卵囊孢子化抑制率大小依次为:百球清＞优求乐＞球抑＞球肠清＞肠球双效,半数效量(EC5o)大小依次为:肠球双效＞球肠清＞球抑＞优求乐＞百球清;(2)5种消毒剂对兔卵囊孢子化抑制率大小依次为:二硫化碳＞苯酚＞氨水＞三氯异氰尿酸＞碘酊,半数效量大小依次为:碘酊＞三氯异氰尿酸＞氨水＞苯酚＞二硫化碳;半数孢子化时间依次为:二硫化碳＞氨水＞苯酚＞三氯异氰尿酸＞碘酊.(3)毒力较强的几种兔球虫卵囊耐药性大小依次为:大型艾美耳球虫＞斯氏艾美耳球虫＞无残艾美耳球虫＞肠型艾美耳球虫.结论 15 mL/L百球清体外作用8h对兔球虫卵囊孢子化抑制效果最强.体积分数6％二硫化碳作用于卵囊4h,抑制兔球虫卵囊孢子化效果最好.兔球虫卵囊耐药性与虫体大小相关,较大虫体对药物敏感性高.     

Calcitonin gene-related peptide-targeting drugs and Raynaud’s phenomenon: a real-world potential safety signal from the WHO pharmacovigilance database

BackgroundMigraine is responsible for significant disability and societal burden. Recently, drugs targeting the calcitonin gene-related peptide (CGRP) pathway raised new hopes. CGRP, a potent vasodilator, plays a key role in the pathogenesis of migraine attacks. The deficiency of CGRP is involved in Raynaud’s phenomenon, which consists of abnormal vasoconstriction of the digits. We aimed to assess the potential association of Raynaud’s phenomenon with CGRP-targeting drugs, analyzing real-world data from the World Health Organization (VigiBase®).MethodsWe queried all reports of Raynaud’s phenomenon involving a CGRP-targeting drug. We sought disproportionate reporting of Raynaud’s phenomenon with these drugs. For this purpose, we relied on the calculation of the Information Component (IC). A positive lower end of the 95% confidence interval (CI) of the IC defines a statistically significant association. As migraine patients are prone to Raynaud’s phenomenon, we also calculated the IC of Raynaud’s phenomenon with CGRP-targeting drugs compared to 5HT1_B/D agonists (triptans), and beta-blockers used in the treatment of migraine.ResultsOverall, 99 reports of Raynaud’s phenomenon involving CGRP-targeting drugs have been yielded in VigiBase®. The most reported CGRP-targeting drug was erenumab, with 56 reports (56.6%). The median time to onset was 84 days. No fatality was notified, but one patient suffered from gangrene and extremity necrosis. As a whole, CGRP-targeting drugs were significantly associated with Raynaud’s phenomenon, with an IC of 3.3 (95%CI: 3.0–3.5). There was a disproportionate reporting of Raynaud’s phenomenon with CGRP-targeting drugs compared to triptans (IC 0.4; 95%CI: 0.1–0.6) and to beta-blockers (IC 0.5; 95%CI: 0.2–0.7) as well.ConclusionsThere is a significant disproportionality signal of Raynaud’s phenomenon with CGRP-targeting. This signal stands out when CGRP-targeting drugs are compared to other drugs used in patients with migraine. This study is limited by missing data in pharmacovigilance reports. CGRP-targeting drugs may be subject to Weber effect and reporting bias. Nonetheless, CGRP blockade might be the last straw that disrupts the physiological balance of vascular response in patients at-risk of Raynaud’s phenomenon. Pending further data regarding vascular safety of CGRP-targeting drugs, caution is warranted in these patients.     

Tetrandrine and arsenic trioxide synergistically inhibit proliferation of HCC1937 triple negative breast cancer cells

Objective

To evaluate the effects of tetrandrine plus arsenic trioxide on HCC1937 cells, a triple negative breast cancer cell line, and to explore possible mechanisms.

抗雄药物诱导性神经内分泌前列腺癌的研究进展

接受新型雄激素受体途径抑制剂（ARPI）的去势抵抗性前列腺癌（CRPC）的患者往往在治疗应答中表现出耐药性,肿瘤获得雄激素受体（AR）-独立亚型,使癌细胞不再依赖于AR通路继续生长。CRPC患者在接受ARPI治疗后,部分患者不仅未达到临床获益,反而出现疾病进展,即神经内分泌前列腺癌（NEPC）,NEPC与不良预后密切相...     

Revolutionary Impact of Nanodrug Delivery on Neuroscience

Brain research is the most expanding interdisciplinary research that is using the state of the art techniques to overcome limitations in order to conduct more accurate and effective experiments. Drug delivery to the target site in the central nervous system (CNS) is one of the most difficult steps in neuroscience researches and therapies. Taking advantage of the nanoscale structure of neural cells (both neurons and glia); nanodrug delivery (second generation of biotechnological products) has a potential revolutionary impact into the basic understanding, visualization and therapeutic applications of neuroscience. Current review article firstly provides an overview of preparation and characterization, purification and separation, loading and delivering of nanodrugs. Different types of nanoparticle bioproducts and a number of methods for their fabrication and delivery systems including (carbon) nanotubes are explained. In the second part, neuroscience and nervous system drugs are deeply investigated. Different mechanisms in which nanoparticles enhance the uptake and clearance of molecules form cerebrospinal fluid (CSF) are discussed. The focus is on nanodrugs that are being used or have potential to improve neural researches, diagnosis and therapy of neurodegenerative disorders.     

Immunomodulation of Fungal β-Glucan in Host Defense Signaling by Dectin-1

During the course of evolution, animals encountered the harmful effects of fungi, which are strong pathogens. Therefore, they have developed powerful mechanisms to protect themselves against these fungal invaders. β-Glucans are glucose polymers of a linear β(1,3)-glucan backbone with β(1,6)-linked side chains. The immunostimulatory and antitumor activities of β-glucans have been reported; however, their mechanisms have only begun to be elucidated. Fungal and particulate β-glucans, despite their large size, can be taken up by the M cells of Peyer''s patches, and interact with macrophages or dendritic cells (DCs) and activate systemic immune responses to overcome the fungal infection. The sampled β-glucans function as pathogen-associated molecular patterns (PAMPs) and are recognized by pattern recognition receptors (PRRs) on innate immune cells. Dectin-1 receptor systems have been incorporated as the PRRs of β-glucans in the innate immune cells of higher animal systems, which function on the front line against fungal infection, and have been exploited in cancer treatments to enhance systemic immune function. Dectin-1 on macrophages and DCs performs dual functions: internalization of β-glucan-containing particles and transmittance of its signals into the nucleus. This review will depict in detail how the physicochemical nature of β-glucan contributes to its immunostimulating effect in hosts and the potential uses of β-glucan by elucidating the dectin-1 signal transduction pathway. The elucidation of β-glucan and its signaling pathway will undoubtedly open a new research area on its potential therapeutic applications, including as immunostimulants for antifungal and anti-cancer regimens.     

Non-steroidal anti-inflammatory drugs in colorectal surgery: A risk factor for anastomotic complications?

In a recent article, Gorissen et al report on 795 patients with primary colorectal anastomosis operated on during the period 2008-2010 for different colorectal conditions at two centres. The leakage rate was significantly higher among patients who were administered non-steroidal anti-inflammatory drugs (NSAIDs) in the perioperative course. A dose-response relationship could also be traced, where longer NSAID use yielded a higher risk of anastomotic breakdown. However, as this study is observational in design, confounding by indication may be present and there is also a risk of residual confounding from unmeasured covariates. Moreover, the question whether different affinity for the cyclooxygenase enzyme is important in different NSAIDs seems to be largely unanswered. The results, conclusions and clinical relevance of the aforementioned study, including the possible effects of different types of NSAIDs, are discussed. While acknowledging that this study represents the best attempt so far in establishing the causal relationship between perioperative NSAID use and anastomotic leakage, the need for further research in this important area is underlined.     

Facts and Fallacies About Measuring Blood Pressure in Rats

Although blood pressure can easily be measured in anesthetized rats by simply connecting a catheter to a pressure transducer, repeated measurements taken over long periods of time in awake rats are much more difficult to make. For chronic experiments two methods are now commonly used: direct recording from chronically-implanted arterial catheters, or indirect measurement with the tail-cuff method. Direct recording of intraarterial pressure can be done continuously and is more accurate, but technically more demanding. On the other hand, although tail-cuff measurements are less accurate, they do not require surgery and can be repeated almost indefinitely. With most tail-cuff methods the rats are preheated to dilate the tail vessels and thereby facilitate pulse detection, but with the new IITC photoelectric sensor indirect measurements of systolic as well as of mean arterial pressure can be made without external preheating. Even with a properly validated tail-cuff method, however, errors can still occur particularly when it is used to quantify modest blood pressure changes like those during development of hypertension, or following administration of vasoactive drugs. To safeguard against such errors, each laboratory should always validate its own tail-cuff method under uniform experimental conditions similar to those existing when the method is actually used. Additionally, all blood pressure differences thereby detected should be verified by direct measurement of intraarterial pressure in the same rats.