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Background: The coronavirus disease (COVID-19) pandemic has accentuated the need for effective clinical skills training in infectious diseases. This study aimed to explore the influencing factors of infectious disease clinical skills training based on scenario simulation teaching for medical staff in China. Methods: This hospital-based, cross-sectional study was conducted at the Third People's Hospital of Shenzhen between March and December 2022. Scenario simulation teaching was applied, and factors such as gender, educational level, professional background, and previous experience were examined to determine their impact on qualification outcomes. Results: The study included participants primarily between the ages of 20–40 years, with a higher proportion of women holding university degrees. Nurses and physicians were more likely to qualify, indicating the significance of professional backgrounds. Women showed a higher likelihood of qualifying than men and higher educational attainment correlated with better qualification rates. Prior experience with protective clothing in isolation wards was a significant determinant of successful qualification. Multivariate analysis underscored the influence of sex, education, and previous experience on training effectiveness. Conclusion: Scenario simulation is an effective strategy for training clinical skills in treating infectious diseases. This study highlights the importance of considering sex, education, professional background, and prior experience when designing training programs to enhance the efficacy and relevance of infectious disease training. [ABSTRACT FROM AUTHOR]

Background: Acute myeloid leukemia (AML) is one of the most common types of adult acute leukemia. Standard chemotherapies can induce complete remission in selected patients; however, a majority of patients eventually relapse and succumb to the disease. Thus, the development of novel therapeutics for AML is urgently needed. Human C-type lectin-like molecule-1 (CLL-1) is a type II transmembrane glycoprotein, and its expression is restricted to myeloid cells and the majority of AML blasts. Moreover, CLL-1 is expressed in leukemia stem cells (LSCs), but absent in hematopoietic stem cells (HSCs), which may provide a potential therapeutic target for AML treatment. Methods: We tested the expression of CLL-1 antigen on peripheral blood cells and bone marrow cells in healthy donor and AML patients. Then, we developed a chimeric antigen receptor (CAR) containing a CLL1-specific singlechain variable fragment, in combination with CD28, 4-1BB costimulatory domains, and CD3-? signaling domain. We further investigate the function of CLL-1 CAR-T cells. Results: The CLL-1 CAR-T cells specifically lysed CLL-1+ cell lines as well as primary AML patient samples in vitro. Strong anti-leukemic activity was observed in vivo by using a xenograft model of disseminated AML. Importantly, CLL-1+ myeloid progenitor cells and mature myeloid cells were specifically eliminated by CLL-1 CAR-T cells, while normal HSCs were not targeted due to the lack of CLL-1 expression. Conclusions: CLL-1 CAR-T represents a promising immunotherapy for the treatment of AML. [ABSTRACT FROM AUTHOR]

Background: Total cholesterol is a well-documented risk factor for coronary disease. Previous studies have shown that high total cholesterol level is associated with better stroke outcomes, but the association of low total cholesterol levels and ischemic stroke outcomes is rare. Therefore, we aimed to assess the association of low total cholesterol levels and stroke outcomes among acute ischemic stroke patients in China.Methods: This study recruited 6407 atherothrombotic infarction patients from Tianjin, China, between May 2005 and September 2014. All patients were categorized into five groups according to TC level quintiles at admission. Differences in subtypes, severity, risk factors, and outcomes at 3, 12, and 36 months after stroke were compared between these groups.Results: In total, 1256 (19.6%) patients had low cholesterol levels, with a higher prevalence in men than in women (23.7% vs. 11.2%, P < 0.001). Compared with higher cholesterol levels, the lowest cholesterol level quintile (TC, <4.07 mmol/L) was associated with older age (64.7 years, P = 0.033), anterior circulation infarct (22.8%), atrial fibrillation (4.9%), current smoking (41.1%), and alcohol consumption (21.1%) and lower frequencies of hypertension (72.9%), diabetes (30.7%), and obesity (9.9%). Dependency and recurrence rates were significantly higher at 36 months in patients in the lowest TC level quintile than in those with higher cholesterol levels (dependency rates, 51.2% vs 45.2%; P = 0.007 and recurrence rates, 46.3% vs 37.3%, P = 0.001). Moreover, these differences remained after adjustment for age, sex, stroke severity, and Oxfordshire Community Stroke Project classification (odds ratios [ORs] for dependency rate, 1.41; 95% confidence interval [CI], 1.11, 1.79; P = 0.005 and recurrence rate, 1.50; 95% CI, 1.19, 1.89; P = 0.001). However, mortality rates after stroke were not significantly different between the groups.Conclusions: These findings suggest that statin treatment for patients with atherothrombotic infarction and low cholesterol levels increase long-term dependency and recurrence rates, but do not increase mortality rates. It is crucial to highlight the different impact of statin treatment on patients with atherothrombotic infarction and lower cholesterol levels for secondary stroke prevention in China. [ABSTRACT FROM AUTHOR]

Background: Stroke is accompanied by a distinguished inflammatory reaction that is initiated by the infiltration of immunocytes, expression of cytokines, and other inflammatory mediators. As natural killer cells (NK cells) are a type of cytotoxic lymphocyte critical to the innate immune system, we investigated the mechanism of NK cells-induced brain injuries after cerebral ischemia and the chemotactic effect of IP-10 simultaneously.Methods: NK cells infiltration, interferon-gamma (IFN-γ) and IP-10 expression were detected by immunohistochemistry, immunofluorescence, PCR and flow cytometry in human and C57/BL6 wild type mouse ischemic brain tissues. The ischemia area was detected via 2,3,5-triphenyltetrazolium chloride staining. CXCR3 mean fluorescence intensity of isolated NK cells was measured by flow cytometry. The neuronal injury made by NK cells was examined via apoptosis experiment. The chemotactic of IP-10 was detected by migration and permeability assays.Results: In human ischemic brain tissue, infiltrations of NK cells were observed and reached a peak at 2 to 5 days. In a permanent middle cerebral artery occlusion (pMCAO) model, infiltration of NK cells into the ischemic infarct region reached their highest levels 12 hours after ischemia. IFN-γ-positive NK cells and levels of the chemokine IP-10 were also detected within the ischemic region, from 6 hours up to 4 days after pMCAO was performed, and IFN-γ levels decreased after NK cells depletion in vivo. Co-culture experiments of neural cells with NK cells also showed that neural necrosis was induced via IFN-γ. In parallel experiments with IP-10, the presence of CXCR3 indicates that NK cells were affected by IP-10 via CXCR3, and the effect was dose-dependent. After IP-10 depletion in vivo, NK cells decreased. In migration assays and permeability experiments, disintegration of the blood-brain barrier (BBB) was observed following the addition of NK cells. Moreover, in the presence of IP-10 this injury was aggravated.Conclusions: All findings support the hypothesis that NK cells participate in cerebral ischemia and promote neural cells necrosis via IFN-γ. Moreover, IP-10 intensifies injury to the BBB by NK cells via CXCR3. [ABSTRACT FROM AUTHOR]

Background: Migraine is a neurological disorder resulting in large socioeconomic burden. This network meta-analysis (NMA) is designed to compare the relative efficacy and tolerability of non-steroidal anti-inflammatory agents (NSAIDs) and triptans., Methods: We conducted systematic searches in database PubMed and Embase. Treatment effectiveness was compared by synthesizing direct and indirect evidences using NMA. The surface under curve ranking area (SUCRA) was created to rank those interventions., Results: Eletriptan and rizatriptan are superior to sumatriptan, zolmitriptan, almotriptan, ibuprofen and aspirin with respect to pain-relief. When analyzing 2 h-nausea-absence, rizatriptan has a better efficacy than sumatriptan, while other treatments indicate no distinctive difference compared with placebo. Furthermore, sumatriptan demonstrates a higher incidence of all-adverse-event compared with diclofenac-potassium, ibuprofen and almotriptan., Conclusion: This study suggests that eletriptan may be the most suitable therapy for migraine from a comprehensive point of view. In the meantime ibuprofen may also be a good choice for its excellent tolerability. Multi-component medication also attracts attention and may be a promising avenue for the next generation of migraine treatment.

Background: Previous studies have shown that total cholesterol (TC) levels are associated with stroke outcomes, but sex differences in the association between TC levels, especially a low TC level, and ischemic stroke outcomes are unknown. We aimed to assess the sex differences in stroke outcomes among patients with atherothrombotic infarctions and low TC levels in China., Methods: This study recruited patients with atherothrombotic infarctions from Tianjin, China, between May 2005 and September 2014. Patients with low TC levels (defined as TC <4.22 mmol/L) were analyzed in this study. Sex differences in stroke subtypes, severity, risk factors, and outcomes at 3 and 12 months after stroke were compared., Results: Overall, 1587 patients with low TC levels were recruited to this study from among 6407 patients with atherothrombotic infarctions listed in a stroke registry. Women were more likely than men to have posterior circulation infarcts, severe stroke, hypertension, and obesity but less likely to be current smokers or to consume alcohol. There were no sex differences in stroke outcomes. Older age and severe stroke were common risk factors for poor outcomes after stroke in this study. The presence of diabetes mellitus was an independent predictor of low mortality at 12 months after stroke, possibly because a drug commonly used to treat diabetes, metformin, enhances angiogenesis. Obesity was the determinant of the recurrence and dependency rates at 12 months after stroke., Conclusions: These findings suggest that patients (both men and women) with atherothrombotic infarction who have low TC levels would not benefit from receiving statin treatment. Therefore, it is crucial to explore the impact of statin treatment on outcomes in Asian patients, especially Chinese patients with atherothrombotic and low TC levels, in order to improve outcomes after stroke and reduce the disease burden.

Background: Circulating follicular helper T (Tfh) cells are a heterogeneous population of CD4 + helper T cells that promotes pathogenic immune responses in autoimmune diseases. In this study, we examined the status of different subpopulations of Tfh cells in peripheral circulation and their associations with various clinical characteristics of IgA vasculitis (IgAV)., Methods: According to the phenotypic expressions of different molecules, focus was given on six subpopulations of Tfh cells: CD4 + CXCR5 + , CD4 + CXCR5 + ICOS + , CD4 + CXCR5 + ICOS + PD-1 + , CD4 + CXCR5 + ICOS high PD-1 high , CD4 + CXCR5 + ICOS - PD-1 + , and CXCR5 + CD45RA - IL-21 + . The frequencies of these six subpopulations and the circulating level of Tfh-related cytokine interleukin 21 (IL-21) were measured from 27 patients with IgAV and 15 healthy controls (HC) by flow cytometry and flow cytometric bead array, respectively., Results: Significantly higher frequencies of CD4 + CXCR5 + , CD4 + CXCR5 + ICOS + , CD4 + CXCR5 + ICOS + PD-1 + , CD4 + CXCR5 + ICOS high PD-1 high and CXCR5 + CD45RA - IL-21 + Tfh cells, as well as higher levels of plasma IL-21, were detected in IgAV patients compared to HC. The level of each Tfh subpopulation varied by the presenting symptoms of IgAV, but did not differ between patients treated or not treated with glucocorticoids. When the disease entered the remission stage following treatment, circulating levels of CD4 + CXCR5 + , CD4 + CXCR5 + ICOS + , CD4 + CXCR5 + ICOS + PD-1 + , CD4 + CXCR5 + ICOS high PD-1 high and CXCR5 + CD45RA - IL-21 + Tfh cells, as well as plasma IL-21 levels were reduced. Among the six subpopulations of Tfh cells, both CD4 + CXCR5 + ICOS + and CXCR5 + CD45RA - IL-21 + significantly and positively correlated with serum IgA and plasma IL-21 levels, but only CXCR5 + CD45RA - IL-21 + significantly and negatively correlated with the serum C4 level., Conclusions: Tfh cells may differentially contribute to the development of IgAV or predict disease progression. These findings provide novel insights in the pathogenesis of IgAV and may benefit treatment development targeting organ-specific presenting symptoms of IgAV.

Background: Total cholesterol is a well-documented risk factor for coronary disease. Previous studies have shown that high total cholesterol level is associated with better stroke outcomes, but the association of low total cholesterol levels and ischemic stroke outcomes is rare. Therefore, we aimed to assess the association of low total cholesterol levels and stroke outcomes among acute ischemic stroke patients in China., Methods: This study recruited 6407 atherothrombotic infarction patients from Tianjin, China, between May 2005 and September 2014. All patients were categorized into five groups according to TC level quintiles at admission. Differences in subtypes, severity, risk factors, and outcomes at 3, 12, and 36 months after stroke were compared between these groups., Results: In total, 1256 (19.6%) patients had low cholesterol levels, with a higher prevalence in men than in women (23.7% vs. 11.2%, P < 0.001). Compared with higher cholesterol levels, the lowest cholesterol level quintile (TC, <4.07 mmol/L) was associated with older age (64.7 years, P = 0.033), anterior circulation infarct (22.8%), atrial fibrillation (4.9%), current smoking (41.1%), and alcohol consumption (21.1%) and lower frequencies of hypertension (72.9%), diabetes (30.7%), and obesity (9.9%). Dependency and recurrence rates were significantly higher at 36 months in patients in the lowest TC level quintile than in those with higher cholesterol levels (dependency rates, 51.2% vs 45.2%; P = 0.007 and recurrence rates, 46.3% vs 37.3%, P = 0.001). Moreover, these differences remained after adjustment for age, sex, stroke severity, and Oxfordshire Community Stroke Project classification (odds ratios [ORs] for dependency rate, 1.41; 95% confidence interval [CI], 1.11, 1.79; P = 0.005 and recurrence rate, 1.50; 95% CI, 1.19, 1.89; P = 0.001). However, mortality rates after stroke were not significantly different between the groups., Conclusions: These findings suggest that statin treatment for patients with atherothrombotic infarction and low cholesterol levels increase long-term dependency and recurrence rates, but do not increase mortality rates. It is crucial to highlight the different impact of statin treatment on patients with atherothrombotic infarction and lower cholesterol levels for secondary stroke prevention in China.

Background: Diabetes has been shown to be significantly associated with poor outcome after stroke. However, the sex differences in stroke outcome among patients with diabetes are unknown. Therefore, we aimed to assess the sex differences in long-term prognosis among acute ischemic stroke patients with diabetes., Methods: The ischemic stroke patients with diabetes were recruited to this study between May 2005 and September 2014 in Tianjin, China. Sex differences in mortality, dependency (modified rank scale > 2), and recurrence at 3, 12, and 36 months after stroke were analyzed., Results: A total of 2360 patients were recruited in this study. The age of stroke onset, National Institute of Health stroke scale (NIHSS), and modified rank scale (mRS) on admission were greater in women than in men (P < 0.05). Women were more likely to have hypertension, obesity, atrial fibrillation, and dyslipidemias. In contrast, men were more likely to have artery stenosis, current smoking, and alcohol consumption (P < 0.001). There was higher mortality in women than in men at 3 months (7.9 % vs 5.2 %), 12 months (12.2 % vs 8.2 %), and 36 months (21.9 % vs 16.1 %) after stroke; but no differences were found in dependency and recurrence. Sex differences were found in associated factors of outcomes by time-point. Trial of Org 10172 in Acute Stroke Treatment (TOAST) of large artery atherothrombosis (LAA), cardioembolism (CE), and smoking were risk factors of outcomes in women at short term and medium term; but atrial fibrillation (AF), obesity, and alcohol were risk factors of outcomes in men at medium term and long term., Conclusions: These findings suggest that it is crucial to establish the individual scheme of therapy for every patient by different risk factors of stroke, strengthen the rehabilitation of stroke, and carry on the health education early for the secondary prevention of stroke in patients with diabetes mellitus (DM).

Background: Use of crude ligninase of bacterial origin is one of the most promising ways to improve the practical biodegradation of lignocellulosic biomass. However, lignin is composed of diverse monolignols with different abundance levels in different plant biomass and requires different proportions of ligninase to realize efficient degradation. To improve activity and reduce cost, the simultaneous submerged fermentation of laccase and lignin peroxidase (LiP) from a new bacterial strain, Streptomyces cinnamomensis, was studied by adopting formulation design, principal component analysis, regression analysis and unconstrained mathematical programming., Results: The activities of laccase and LiP from S. cinnamomensis cultured with the optimal medium formulations were improved to be five to eight folders of their initial activities, and the measured laccase:LiP activity ratios reached 0.1, 0.4 and 1.7 when cultured on medium with formulations designed to produce laccase:LiP complexes with theoretical laccase:LiP activity ratios of 0.05 to 0.1, 0.5 to 1 and 1.1 to 2., Conclusion: Both the laccase and LiP activities and also the activity ratio of laccase to LiP could be controlled by the medium formulation as designed. Using a crude laccase-LiP complex with a specially designed laccase:LiP activity ratio has the potential to improve the degradation of various plant lignins composed of diverse monolignols with different abundance levels.

Background: Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-activated transcription factor, which regulates gene expression of the key proteins involved in lipid metabolism, vascular inflammation, and proliferation. PPARgamma may contribute to attenuating atherogenesis and postangioplasty restenosis. PPARgamma C161-->T substitution is associated with a reduced risk of coronary artery disease (CAD). Whether or not the gene substitution alters the risk of CAD in type 2 diabetes mellitus (T2DM) patients remains unclear., Methods: A total of 556 unrelated subjects from a Chinese Han population, including 89 healthy subjects, 78 CAD patients, 86 T2DM patients, and 303 CAD combined with T2DM patients, were recruited to enroll in this study. PPARgammaC161-->T gene polymorphism was determined by polymerase chain reaction and restriction fragment length polymorphisms. Plasma levels of lipoproteins, apolipoproteins, glucose, and insulin were measured by ELISA or radioimmunoassay (RIA). The coronary artery lesions were evaluated by coronary angiography., Results: The frequency of the 161T allele in CAD, T2DM, and CAD combined with T2DM patients was similar to that observed in the healthy control group. However, in CAD combined with T2DM patients, the group with angiographically documented moderate stenoses had a higher frequency of the 161T allele in comparison to the group with severe stenoses (P < 0.05). Moreover, in CAD with T2DM patients, the triglyceride levels and apoB in CC homozygote carriers were significantly higher than those in "T" allele carriers., Conclusions: PPARgammaC161-->T genotypes weren't significantly associated with the risk of CAD, but were markedly correlated with severity of disease vessels in patients with CAD and T2DM. Furthermore, PPARgammaC161-->T substitution was associated with an altered adipose, but not glucose metabolism. These results indicate that the PPARgamma C161-->T polymorphism may reduce the risk of severe atherogenesis by modulation of adipose metabolism, especially triglycerides and apoB, in Chinese patients with CAD and T2DM.