In order to standardize the clinical application of compound opioid analgesics, Association for the Study of Pain (CASP) published the Chinese expert concensus on the clinical application of compound opioid analgesics and the concensus has been widely concerned since its publication in 2018. This article briefly introduces the consensus of the background and main contents, and mainly discusses the drug composition, pharmacological action, clinical reasonable application, use in the special population, adverse reactions of compound opioid analgesics, and provides a reference for clinical application.
Key words:
Drug combinations; Analgesics, opoid; Guidebooks; China
The repetitive activation of T cells (priming) enhances the expression of many cytokines, such as IL-4, but not others, such as IL-2. Molecular mechanisms underlying selective expression of cytokines by T cells remain poorly understood. Here we show that priming of CD4 T cells selectively enhances IL-4 expression relative to IL-2 expression by a transcriptional mechanism involving nuclear factor of activated T cells (NFAT) proteins. As detected by in vivo footprinting, priming markedly increases the activation-dependent engagement of the P0 and P1 NFAT-binding elements of the IL-4 promoter. Moreover, each proximal P element is essential for optimal IL-4 promoter activity. Activated primed CD4 T cells contain more NFAT1 and support greater NFAT-directed transcription than unprimed CD4 T cells, while activator protein 1 binding and activator protein 1-mediated transcription by both cell types is similar. Increased expression of wild-type NFAT1 substantially increases IL-4 promoter activity in unprimed CD4 T cells, suggesting NFAT1 may be limiting for IL-4 gene expression in this cell type. Furthermore, a truncated form of NFAT1 acts as a dominant-negative, reducing IL-4 promoter activity in primed CD4 T cells and confirming the importance of endogenous NFAT to increased IL-4 gene expression by effector T cells. NFAT1 appears to be the major NFAT family member responsible for the initial increased expression of IL-4 by primed CD4 T cells.
Abstract A published clinical trial of veledimex (V)-regulatable interleukin-12 (IL-12) gene therapy (“Controlled IL-12”) under the control of a transcriptional switch (RheoSwitch Therapeutic Systemâ, RTSâ) as monotherapy in recurrent glioblastoma (rGBM) showed sustained infiltration of activated T cells within the tumor months after treatment (Sci Transl Med. 2019;11(505)). These T cells demonstrated up-regulation of immune checkpoint signaling, providing a rationale for combination therapy with the PD-1 inhibitor, nivolumab (nivo). We report interim findings following completion of enrollment (with follow-up ongoing) for a multi-institutional, open label, dose-escalation phase 1 trial (NCT03636477) evaluating safety and tolerability of loco-regional Controlled IL-12 in combination with nivo in adults with rGBM. Replication-incompetent adenovirus coding for RTS-IL-12 (Ad) was administered during surgery by free-hand injection into the tumor and periphery (2 x 1011 viral particles, Day 0) accompanied by V (10 or 20 mg) PO QD x 15 (Days 0 to 14) in combination with nivo (1 or 3 mg/kg) IV on Days -7, 15, then Q2W. Twenty-one subjects were treated (Cohort 1: V 10 mg, nivo 1 mg/kg, n=3; Cohort 2: V 10 mg, nivo 3 mg/kg, n=3; and Cohort 3: V 20 mg, nivo 3 mg/kg, n=3 & 12 in expansion). Safety data were comparable to Ad+V monotherapy. Adverse reactions (ARs) during follow-on nivo dosing were consistent with nivo labeling. ARs were manageable and generally reversible with no synergistic toxicities. Updated overall survival findings will be presented. Baseline and post-treatment histochemical staining and multiplex immunofluorescence analyses for a subgroup of subjects will be discussed. The safety of this combination immunotherapy has been established, leading to a currently accruing phase 2 clinical trial of loco-regional Controlled IL-12 gene therapy in combination with the PD-1 inhibitor cemiplimab-rwlc (NCT 04006119).
Cancer proteomics has become a powerful technique for characterizing the protein markers driving transformation of malignancy, tracing proteome variation triggered by therapeutics, and discovering the novel targets and drugs for the treatment of oncologic diseases. To facilitate cancer diagnosis/prognosis and accelerate drug target discovery, a variety of methods for tumor marker identification and sample classification have been developed and successfully applied to cancer proteomic studies. This review article describes the most recent advances in those various approaches together with their current applications in cancer-related studies. Firstly, a number of popular feature selection methods are overviewed with objective evaluation on their advantages and disadvantages. Secondly, these methods are grouped into three major classes based on their underlying algorithms. Finally, a variety of sample separation algorithms are discussed. This review provides a comprehensive overview of the advances on tumor maker identification and patients/samples/tissues separations, which could be guidance to the researches in cancer proteomics.
This paper intends to examine the establishment and transformation of Quangos(Quasi-Autonomous Non-Governmental Organizations) in transitional China. Regarding Quango, China slightly differs from the western countries due to China's unique social context. We suggest that the Quango Continuum could be slightly modified to apply better to China. The second part of the paper presents the China quasi-autonomous organizations, their main characteristics, and the reforms that have concerned these organizations. An overview of the main political, economic, social and legal reforms as well as globalization undertaken will be given, to place Quangos in the administrative context in which they act. Finally the paper takes trade associations as an example to examine their establishment and transformation. They are typical Quango that spends public money to fulfill a public task but with some degree of independence from elected representatives. Most of them are created from top to bottom. Trade associations thus generally demonstrate the characters of stronger government especially during China's transitional period. However, the government begins to encourage trade associations to seek independence in their finance, personnel, and activities recently in order to reduce its financial pressure. The trend is clear that they are becoming increasingly independent with the deepening of China's reform.
Strong El Niño events alter tropical climates and may lead to a negative carbon balance in tropical forests and consequently a disruption to the global carbon cycle. The complexity of tropical forests and the lack of data from these regions hamper the assessment of the spatial distribution of El Niño impacts on these ecosystems. Typically, maps of climate anomaly are used to detect areas of greater risk, ignoring baseline climate conditions and forest cover. Here, we integrated climate anomalies from the 1982–1983, 1997–1998, and 2015–2016 El Niño events with baseline climate and forest edge extent, using a risk assessment approach to hypothetically assess the spatial and temporal distributions of El Niño risk over tropical forests under several risk scenarios. The drivers of risk varied temporally and spatially. Overall, the relative risk of El Niño has been increasing driven mainly by intensified forest fragmentation that has led to a greater chance of fire ignition and increased mean annual air temperatures. We identified areas of repeated high risk, where conservation efforts and fire control measures should be focused to avoid future forest degradation and negative impacts on the carbon cycle.
Objective
To investigate the prevalence and epidemiologic characteristics of diabetes mellitus and prediabetic state among the adults in Shandong province.
Methods
It was a cross-sectional and cluster sampling investigation. From May to July in 2008, a total of 3011 residents( 1328 males and 1683 females), aged 20 years and above(20-76 yrs, mean (51±12) yrs), from 4 regions in Shandong province were enrolled in this study. After an overnight fast, participants underwent an oral glucose-tolerance test. The fasting and 2-hour plasma glucose levels were measured to identify undiagnosed diabetes and prediabetes. Prevalence of diabetes and prediabetes and fat metabolism were compared by subgroups according to sex, age (10 years for an interval). One-way ANOVA was applied to compare differences of continuous variables between subgroups. Rates were compared by using the Chi-Square test.
Results
The crude prevalence estimates of diabetes and prediabetes in this survey was 12.6%(378/3011) and 8.8%(266/3011), respectively. When adjusted for age and sex, the prevalence was 9.9% (10.9% for men and 8.8% for women) for diabetes and 7.3% for prediabetes (7.6% for men and 6.9% for women). There was no significant differences in prevalence of diabetes and prediabetes between males and females (χ2=0.225, 0.184, both P>0.05). The prevalence of diabetes increased with age in men and women (χ2=57.296, 109.882, both P<0.05). The newly-diagnosed diabetes (n=276) accounted for 41.3% of the total diabetes. The prevalence of isolated impaired glucose tolerance was higher than that of isolated impaired fasting glucose(74.1% vs 16.9%). The prevalence of diabetes was higher in urban residents than that in rural residents (13.5% vs 10.9%, χ2=4.25, P<0.05). The multivariable analysis showed that age, family history of diabetes, central obesity, systolic blood pressure, heart rate, triglyceride and low density lipoprotein cholesterol were the risk factors for development of glucose metabolism disorder (OR=1.623, 2.150, 1.758, 1.132, 1.214, 1.130, 1.171, respectively, all P<0.05), and high density lipoprotein cholesterol was the protective factor (OR=0.617, P<0.05).
Conclusions
The prevalence of diabetes and prediabetes is 9.9% and 7.3 respectively in Shandong. More effective measures should be taken for the prevention, early diagnosis and treatment of diabetes and prediabetes.
Key words:
Diabetes mellitus; Prediabetic state; Prevalence; Epidemiology
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)