Safety of interferon β-1a for treatment of COVID-19： a real-world study based on FAERS database / 上海预防医学

ObjectiveTo systematically evaluate the safety of interferon β-1a for treatment of corona virus disease 2019 （COVID-19）， and to provide references for interferon β-1a's clinical application. MethodsThis study was conducted with the database from US Food and Drug Administration adverse event reporting system （FAERS） from January 1， 2015 to March 31， 2021. Information component （IC） and reporting odds ratio （ROR） methods were applied for signal mining. ResultsA total of 463 700 records of COVID-19 were selected for analysis， and 45 positive drug adverse event signals were detected. Headache （IC025=1.09， ROR025=2.28）， pyrexia （IC025=0.51， ROR025=1.51） and multiple sclerosis relapse （IC025=3.67， ROR025=14.71） were positive adverse events with higher frequency. Autoimmune disorder （IC025=4.42， ROR025=24.03）， streptococcal infection （IC025=4.12， ROR025=19.82）， and multiple sclerosis relapse （IC025=3.67， ROR025=14.71） were positive adverse events. Acute lung injury， cardio-respiratory arrest and metabolic acidosis were associated with a higher proportion and frequency of death. ConclusionThere are certain safety issues with interferon β-1a in the treatment of COVID-19， and some adverse events with high frequency and high death rate deserve further attention by medical staffs.

Screening and evaluation of quality markers from Shuangshen Pingfei formula for idiopathic pulmonary fibrosis using network pharmacology and pharmacodynamic, phytochemical, and pharmacokinetic analyses.

BACKGROUND: The Shuangshen Pingfei formula (SSPF), a classic Chinese medicine derivative formula, has been shown to exert therapeutic effects on idiopathic pulmonary fibrosis (IPF). However, the quality control compounds of SSPF remain unclear. PURPOSE: To select and confirm Q-markers of SSPF based on network pharmacology, cytobiology, animal-based pharmacodynamics, and phytochemical and pharmacokinetic analyses. METHODS: A compound-target network was constructed based on previous research. In addition, high-degree compounds of SSPF were chosen as potential Q-marker candidates. Animal and cytological experiments were performed to verify key targets of IPF. Haematoxylin-eosin and Masson's trichrome staining were used to observe lung tissue pathology. Cytokine levels in the bronchoalveolar lavage fluid (BALF) were measured using ELISA kits. Gene and protein expression levels were determined using PCR and western blotting, respectively. The contents of Q-marker candidates in different batches of SSPF were then determined for traceability research, and the quality consistency of SSPF was objectively evaluated using principal component analysis (PCA). Finally, pharmacokinetic research was performed, and candidates with desirable metabolite and bioavailability parameters were confirmed as Q-markers of SSPF. RESULTS: The compound-target network included 56 compounds and 14 therapeutic targets. Animal experiments showed that SSPF attenuates lung fibrosis. SSPF decreased CC motif chemokine 2 (CCL2) and CC chemokine receptor type 2 (CCR2) levels in the BALF and downregulated the gene and protein expression of IPF therapy-related molecules, such as 5-hydroxytryptamine receptor 2A (HTR2A), CCL2, and CCR2, in the lungs. Cell experiments showed that nine Q-marker candidates in SSPF regulated the expression of CCL2 and CCR2, as predicted. Phytochemical analysis and PCA indicated that the qualities of SSPF in the nine batches were relatively stable. Pharmacokinetic studies demonstrated that mangiferin, salvianolic acid B, tanshinone IIA, naringin, and glycyrrhizic acid could be effectively absorbed into rat plasma, which ensured desirable bioavailability and confirmed their roles as Q-markers to represent anti-pulmonary fibrotic activity. CONCLUSION: Our study is an integrated strategy, based on network pharmacology with experimental verification and phytochemical and pharmacokinetic analyses that provides a novel approach for Q-marker selection and validation of SSPF for IPF treatment.

Intravenous route to choroidal neovascularization by macrophage-disguised nanocarriers for mTOR modulation

Retinal pigment epithelial (RPE) is primarily impaired in age-related macular degeneration (AMD), leading to progressive loss of photoreceptors and sometimes choroidal neovascularization (CNV). mTOR has been proposed as a promising therapeutic target, while the usage of its specific inhibitor, rapamycin, was greatly limited. To mediate the mTOR pathway in the retina by a noninvasive approach, we developed novel biomimetic nanocomplexes where rapamycin-loaded nanoparticles were coated with cell membrane derived from macrophages (termed as MRaNPs). Taking advantage of the macrophage-inherited property, intravenous injection of MRaNPs exhibited significantly enhanced accumulation in the CNV lesions, thereby increasing the local concentration of rapamycin. Consequently, MRaNPs effectively downregulated the mTOR pathway and attenuate angiogenesis in the eye. Particularly, MRaNPs also efficiently activated autophagy in the RPE, which was acknowledged to rescue RPE in response to deleterious stimuli. Overall, we design and prepare macrophage-disguised rapamycin nanocarriers and demonstrate the therapeutic advantages of employing biomimetic cell membrane materials for treatment of AMD.

Atrial fibrillation in critically ill patients who received prolonged mechanical ventilation: a nationwide inpatient report

Background/Aims@#To evaluate temporal trends of atrial fibrillation (AF) prevalence in critically ill patients who received prolonged mechanical ventilation (MV) in the United States. @*Methods@#We used the 2008 to 2014 National Inpatient Sample to compute the weighted prevalence of AF among hospitalized adult patients on prolonged MV. We used multivariable-adjusted models to evaluate the association of AF with clinical factors, in-hospital mortality, hospitalization cost, and length of stay (LOS). @*Results@#We identified 2,578,165 patients who received prolonged MV (21.27% of AF patients). The prevalence of AF increased from 14.63% in 2008 to 24.43% in 2014 (p for trend < 0.0001). Amongst different phenotypes of critically ill patients, the prevalence of AF increased in patients with severe sepsis, asthma exacerbation, congestive heart failure exacerbation, acute stroke, and cardiac arrest. Older age, male sex, white race, medicare access, higher income, urban teaching hospital setting, and Western region were associated with a higher prevalence of AF. AF in critical illness was a risk factor for in-hospital death (odds ratio, 1.13; 95% confidence interval, 1.11 to 1.15), but in-hospital mortality in critically ill patients with AF decreased from 11.6% to 8.3%. AF was linked to prolonged LOS (2%, p < 0.0001) and high hospitalization cost (4%, p < 0.0001). LOS (–1%, p < 0.0001) and hospitalization cost (–4%, p < 0.0001) decreased yearly. @*Conclusions@#The prevalence of comorbid AF is increasing, particularly in older patients. AF may lead to poorer prognosis, and high-quality intensive care is imperative for this population.

Correlation between the changes of regulatory T cells in peripheral blood and disease activity measures in rheumatoid arthritis / 中华风湿病学杂志

Objective:To investigate the level of regulatory T (Treg) cells of peripheral blood and evaluate the correlation between Treg cells and disease activity in rheumatoid arthritis (RA) to further clarify the role of Treg cells in the pathogenesis of RA.Methods:The participants included 300 patients with RA, from the Second Hospital of Shanxi Medical University between January 2016 and September 2018 and 100 gender and age matched healthy individuals. The absolute numbers and proportion of Treg cells and helper T (Th) 17 cells and the ratio of Th17/Treg in peripheral blood of these individuals were detected by flow cytometry combined with standard absolute counting beads. Main statistical analysis methods were t test, spearman correlation and rank sum test. Results:Patients with RA had lower absolute numbers [(35±13) cells/μl vs (26±17) cells/μl, t=4.815, P<0.01] and percentage [(5.1±1.5)% vs (4.4±2.0)%, t=4.111, P<0.01] of Treg cells compared with those in healthy controls, while the number ( t=1.114, P=0.266) and proportion ( t=1.577, P=0.116) of Th17 cells were not significantly changed. RA patients, regardless of new onset (no prior treatment) or treatment with immunosuppressants, had significantly lower absolute numbers of Treg cells [healthy controls (35±13) cells/μl; the Treg cells in new onset patients was (31±17) cells/μl, t=1.974, P=0.049; Treg cells in treated patients was (24±16) cells/μl, t=5.978, P<0.01] but not Th17 cells than healthy controls. With the increase of disease activity score uses 28 joint counts (DAS28), the absolute counts of peripheral Treg cells trended to decrease [remission group (33±15) cells/μl, low activity group (31±17) cells/μl, moderate activity group (28±17) cells/μl, high activity group (24±16) cells/μl], and were negatively correlated with DAS28( r=-0.139, P=0.016) and erythrocyte sedimentation rate (ESR) ( r=-0.116, P=0.046). Conclusion:The absolute counts of peripheral Treg cells decreased significantly, which are associated directly with the pathogenesis of RA rather than high-dose glucocorticoids or immunosuppressive agents. Changes in circulating Treg cells number may play a prominent role in the disease process of RA, which provides clinical basis for evaluation of disease activity and exploration of new effective therapies.

Progress in research on pathogenic genes of retinitis pigmentosa / 中华眼底病杂志

Retinitis pigmentosa (RP) is a group of hereditary blinding fundus diseases caused by abnormalities in photoreceptors of the retina.RP is highly heterogeneous in hereditary and cdinical phenotypes.It can be divided into simple type RP and syndrome type RP.The main inheritance patterns are autosomal dominant,autosomal recessive inheritance and X-linked inheritance.With the popularization and clinical application of gene sequencing technology,more and more disease-causing genes have been discovered,and these genes are mainly expressed in photoreceptor cells and retinal pigment epithelial cell.ln-depth understanding of RP pathogenic genes not only provides a theoretical basis for RP diagnosis and genetic counseling,but also provides guidance for RP gene therapy.

SWOT analysis on the development and utilization of Li medicine resources in Hainan Province / 药学实践杂志

Objective To study the development and utilization of Li medicine resources in Hainan Province, analyze the existing problems and present specific suggestions for the rational exploitation and utilization of Li medicine resources.Methods SWOT analysis was carried out on the development and utilization of Li medicine in Hainan by means of literature analysis and field survey.Results The advantage of Li medicine lies in its long history and sufficient resources.The complicated ethnic factors within Li nationality hindered the development of Li medicine and resulted in the lack of basic research.Although the relevant policies and market demands have brought opportunities for the development of Li medicine, the rapid development of society may pose a potential threat to the development and protection of Li medicine resources.Conclusion The unique advantages of Li medicine ought to be used to create Li medicine brand.While Hainan is building its international tourism island, the health benefits of Li medicine should be promoted.Through the creation of Li medicine schools or departments, new professionals need to be trained to continue the development and utilization of Li medicine.