Low body weight is associated with poor prognosis in patients with chronic obstructive pulmonary disease (COPD). However, it is not known whether gender modifies this relationship.
We pooled data of ...8686 COPD patients from 7 studies with a median length of 36-months of follow up. Using a longitudinal natural cubic spline regression model, we examined the dose-response relationship between body mass index (BMI) and the rate of decline in forced expiratory volume in one second (FEV
) in patients with GOLD 1 and 2 disease, stratified by gender and adjusted for age, smoking status, and cohort effects.
There was an inverse linear relationship between BMI and the rate of FEV
decline in GOLD Grades 1 and 2, which was modified by gender (p < 0.001). In male patients, an increase of BMI by 1 kg/m
reduced FEV
decline by 1.05 mL/year (95% CI 0.96, 1.14). However, in female patients, BMI status did not have a clinically meaningful impact on FEV
decline: an increase of baseline BMI by 1 kg/m
reduced FEV
decline by 0.16 ml/year (95% CI 0.11, 0.21). These gender-modified relationships were similar between GOLD 1 and 2 patients, and between current and former smokers.
In mild to moderate COPD, higher BMI was associated with a less rapid decline of FEV
in male patients whereas this association was minimal in females patients. This gender-specific BMI effect was independent of COPD severity and smoking status.
Increasing evidence suggests that the NLRP3 (nucleotide oligomerization domain-like receptor family, pyrin domain containing 3) inflammasome participates in cardiovascular diseases. However, its role ...and activation mechanism during hypertension remains unclear. In this study, we tested the role and mechanism of calcium-sensing receptor (CaSR) in NLRP3 inflammasome activation during hypertension. We observed that the expressions of CaSR and NLRP3 were increased in spontaneous hypertensive rats (SHRs) along with aortic fibrosis. In vascular smooth muscle cells (VSMCs), the activation of NLRP3 inflammasome associated with CaSR and collagen synthesis was induced by angiotensin II (Ang II). Furthermore, inhibition of CaSR and NLRP3 inflammasome attenuated proinflammatory cytokine release, suggesting that CaSR-mediated activation of the NLRP3 inflammasome may be a therapeutic target in aortic dysfunction and vascular inflammatory lesions.
Cold-dampness Syndrome (RA-Cold) and Hot-dampness Syndrome (RA-Hot) are two distinct groups of rheumatoid arthritis (RA) patients with different clinical symptoms based on traditional Chinese ...medicine (TCM) theories and clinical empirical knowledge. However, the biological basis of the two syndromes has not been fully elucidated, which may restrict the development of personalized medicine and drug discovery for RA diagnosis and therapy.
An integrative strategy combining clinical transcriptomics, phenomics, and metabolomics data based on clinical cohorts and adjuvant-induced arthritis rat models was performed to identify novel candidate biomarkers and to investigate the biological basis of RA-Cold and RA-Hot.
The main clinical symptoms of RA-Cold patients are joint swelling, pain, and contracture, which may be associated with the dysregulation of T cell-mediated immunity, osteoblast differentiation, and subsequent disorders of steroid biosynthesis and phenylalanine metabolism. In contrast, the main clinical symptoms of RA-Hot patients are fever, irritability, and vertigo, which may be associated with various signals regulating angiogenesis, adrenocorticotropic hormone release, and NLRP3 inflammasome activation, leading to disorders of steroid biosynthesis, nicotinamide, and sphingolipid metabolism. IL17F, 5-HT, and IL4I1 were identified as candidate biomarkers of RA-Cold, while S1P and GLNS were identified as candidate biomarkers of RA-Hot.
The current study presents the most comprehensive metabonomic and transcriptomic profiling of serum, urine, synovial fluid, and synovial tissue samples obtained from RA-Cold and RA-Hot patients and experimental animal models to date. Through the integration of multi-omics data and clinical independent validation, a list of novel candidate biomarkers of RA-Cold and RA-Hot syndromes were identified, that may be useful in improving RA diagnosis and therapy.
Existing traditional Chinese medicine (TCM)-related databases are still insufficient in data standardization, integrity and precision, and need to be updated urgently. Herein, an Encyclopedia of ...Traditional Chinese Medicine version 2.0 (ETCM v2.0, http://www.tcmip.cn/ETCM2/front/#/) was constructed as the latest curated database hosting 48,442 TCM formulas recorded by ancient Chinese medical books, 9872 Chinese patent drugs, 2079 Chinese medicinal materials and 38,298 ingredients. To facilitate the mechanistic research and new drug discovery, we improved the target identification method based on a two-dimensional ligand similarity search module, which provides the confirmed and/or potential targets of each ingredient, as well as their binding activities. Importantly, five TCM formulas/Chinese patent drugs/herbs/ingredients with the highest Jaccard similarity scores to the submitted drugs are offered in ETCM v2.0, which may be of significance to identify prescriptions/herbs/ingredients with similar clinical efficacy, to summarize the rules of prescription use, and to find alternative drugs for endangered Chinese medicinal materials. Moreover, ETCM v2.0 provides an enhanced JavaScript-based network visualization tool for creating, modifying and exploring multi-scale biological networks. ETCM v2.0 may be a major data warehouse for the quality marker identification of TCMs, the TCM-derived drug discovery and repurposing, and the pharmacological mechanism investigation of TCMs against various human diseases.
An updated ETCM v2.0 database may be a major data warehouse for quality marker identification and pharmacological mechanism investigation of TCMs against human diseases, and TCM-derived drug discovery and repurposing. Display omitted
The economic burden of interstitial lung disease (ILD) is unknown, limiting informed resource allocation and planning. We sought to conduct the first systematic review on the direct, indirect, and ...overall costs associated with ILD and to evaluate the cost-effectiveness of current therapies globally.
We conducted systematic reviews of ILD disease cost studies and cost-effectiveness analyses (CEAs) using MEDLINE, Embase, and Web of Science databases between 2000 and 2020. We compared ILD costs between countries according to the share of costs towards each country's respective gross domestic product (GDP) per capita. Costs are reported in 2020 USD.
We identified 25 disease cost studies and 7 CEAs. The direct medical costs ranged between $1824 and $116,927 annually per patient (median $32,834; 14-180% of GDP per capita in Western countries). The leading drivers of direct costs were inpatient (55%), outpatient (22%), and medication costs (18%), based on pooled estimates. Annual indirect costs ranged from $7149 to $10,902 per employed patient (median $9607; 12-23% of GDP per capita). Among the 7 CEAs, only 1 study (14%) showed an ILD therapy (ambulatory oxygen) was cost-effective compared to best supportive care.
The direct and indirect costs associated with ILD are consistently high in all countries with available data, with cost-effectiveness profiles of new therapies generally undesirable. Globally, the median total direct cost for ILD equates to 51% of a country's GDP per capita and has been increasing over time.
Detection of characteristic species released from over-heated PVC cables may enable early warning of electrical fire. This work identified the major volatile species for over-heated PVC cables, and ...verified their potential as fire signatures with metal oxide gas sensors. Semi-volatile Dioctyl phthalate (DOP) and 2-Ethylhexanol (2-EH) were found to be ubiquitously present in the cable vapors as major species. Detection of these species and the vapors of overheated cables was accomplished with a metal oxide gas sensor. The response of the gas sensor to the cable vapors resulted mainly from DOP and 2-EH, demonstrating them as effective signature gases for over-heated PVC cables. A gas sensor based on SnO2 nanofibers was prepared with greatly enhanced response to the signature gases. Large-scale simulation tests showed that the nanofiber gas sensor could effectively detect the cable overheating at an early stage.
Sodium taurocholate cotransporting polypeptide (NTCP) has been reported as a functional receptor for hepatitis B virus (HBV) infection. However, HBV could not efficiently infect HepG2 cells ...expressing NTCP (NTCP-HepG2 cells) under adherent monolayer-cell conditions. In this study, NTCP was mainly detected in the basolateral membrane region, but not the apical site, of monolayer NTCP-HepG2 cells. We hypothesized that non-adherent cell conditions of infection would enhance HBV infectivity. Non-adherent NTCP-HepG2 cells were prepared by treatment with trypsin and EDTA, which did not degrade NTCP in the membrane fraction. HBV successfully infected NTCP-HepG2 cells at a viral dose 10 times lower in non-adherent phase than in adherent phase. Efficient infection of non-adherent NTCP-HepG2 cells with blood-borne or cell-culture-derived HBV was observed and was remarkably impaired in the presence of the myristoylated preS1 peptide. HBV could also efficiently infect HepaRG cells under non-adherent cell conditions. We screened several compounds using our culture system and identified proscillaridin A as a potent anti-HBV agent with an IC50 value of 7.2 nM. In conclusion, non-adherent host cell conditions of infection augmented HBV infectivity in an NTCP-dependent manner, thus providing a novel strategy to identify anti-HBV drugs and investigate the mechanism of HBV infection.
This article argues that the neoliberal family novel is by genre compromised to criticize fossil fuel extraction. I situate the claim against the rise of petrocultures studies, especially of novels ...consciously engaged with the post-9/11 extractivist boom. A good number of these novels are family saga, and this article focuses on two of them: Jonathan Franzen's Freedom and Lamar Herrin's Fractures-the latter claimed to resemble Freedom but disproportionally underexplored. This article shows that the family thread in both novels tend to overpower and consume the ecopolitical thread, thereby undercutting the novels' critical force against petrocultures. In demonstrating this point, I trace the evolving cultural construction of the (nuclear) family in relation to the postwar oil boom and the subsequent installation of neoliberalism. Then I show that the novels participate respectively in two modes of neoliberal family construction: a privatized consumer space detached from ecopolitical controversy, or a fully integrated neoliberal stronghold devouring anti-oil resistance. Either way, the textual mobilization of family logic and sentimentalized symbolism jeopardizes the anti-oil theme. Finally, as a way out, I identify an alternative coalitional structure of local anonymity at the end of Fractures that is potentially better positioned to articulate anti-oil politics.
Tianhe Zhuifeng Gao (TZG) shows a satisfying therapeutic efficacy in treating arthromyodynia, which shares similar etiology to myofascial pain syndrome (MPS). We herein aim to explore whether TZG ...could be a potential prescription for MPS therapy. An MPS rat model was successfully established presenting with reduced pain thresholds, abnormal local switch responses, etc., which was effectively reversed by TZG treatment externally. A transcriptome sequencing based on the active MTrPs samples of rats, combined with network analysis revealed that TZG might ameliorate the progression of MPS by impairing neutrophil extracellular traps (NETs) release through inhibiting PI3K-RAC2 signaling to reduce NADPH oxidase-originated ROS. Experimentally, the expression levels of inducers, biomarkers of NETs formation and vessel injury, and p-PI3K, p-P47, and RAC2 proteins were all significantly up-regulated in affected tissues, which were markedly reversed by TZG. Our results not only shed light into broadening the clinical indications of TZG, but benefit MPS therapy.
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•TZG treatment obviously alleviated disease severity of MPS rats•TZG may impair PI3K-RAC2 axis-mediated NETs formed in MPS rats•This study shed light into broadening the clinical indications of TZG
Drugs; Neuroscience; Model organism
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