Associations between Life's Essential 8 and abdominal aortic calcification among US Adults: a cross-sectional study.

BACKGROUND: Cardiovascular health (CVH) and abdominal aortic calcification (AAC) are closely linked to cardiovascular disease (CVD) and related mortality. However, the relationship between CVH metrics via Life's Essential 8 (LE8) and AAC remains unexplored. METHODS: The study analyzed data from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) cohort, which included adults aged 40 or above. The research used the LE8 algorithm to evaluate CVH. Semi-quantitative AAC-24 scoring techniques were employed to assess AAC, categorized into no calcification, mild to moderate calcification, and severe calcification. RESULTS: The primary analysis involved 2,478 participants. Following adjustments for multiple factors, the LE8 score exhibited a significant association with ACC risk (Mild-moderate ACC: 0.87, 95% CI: 0.81,0.93; Severe ACC: 0.77, 95% CI: 0.69,0.87, all P < 0.001), indicating an almost linear dose-response relationship. Compared to the low CVH group, the moderate CVH group showed lower odds ratios (OR) for mild-moderate and severe calcification (OR = 0.78, 95% CI: 0.61-0.99, P = 0.041; OR = 0.68, 95% CI: 0.46-0.99, P = 0.047, respectively). Moreover, the high CVH group demonstrated even lower ORs for mild-moderate and severe calcification (OR = 0.46, 95% CI: 0.31, 0.69, P < 0.001; OR = 0.29, 95% CI: 0.14, 0.59, P = 0.001, respectively). Interactions were found between chronic kidney disease (CKD) condition, history of CVD, marital status and CVH metrics to ACC. Participants without CKD exhibited a more pronounced negative association between the CVH metric and both mild-moderate and severe ACC. Those lacking a history of CVD, and never married/widowed/divorced/separated showed a stronger negative association between the CVH metric and severe ACC. CONCLUSIONS: The novel CVH metrics demonstrated an inverse correlation with the risk of AAC. These findings suggest that embracing improved CVH levels may assist in alleviating the burden of ACC.

Single-cell RNA sequencing reveals cell type-specific immune regulation associated with human neuromyelitis optica spectrum disorder.

Introduction: One rare type of autoimmune disease is called neuromyelitis optica spectrum disorder (NMOSD) and the peripheral immune characteristics of NMOSD remain unclear. Methods: Here, single-cell RNA sequencing (scRNA-seq) is used to characterize peripheral blood mononuclear cells from individuals with NMOSD. Results: The differentiation and activation of lymphocytes, expansion of myeloid cells, and an excessive inflammatory response in innate immunity are observed. Flow cytometry analyses confirm a significant increase in the percentage of plasma cells among B cells in NMOSD. NMOSD patients exhibit an elevated percentage of CD8+ T cells within the T cell population. Oligoclonal expansions of B cell receptors are observed after therapy. Additionally, individuals with NMOSD exhibit elevated expression of CXCL8, IL7, IL18, TNFSF13, IFNG, and NLRP3. Discussion: Peripheral immune response high-dimensional single-cell profiling identifies immune cell subsets specific to a certain disease and identifies possible new targets for NMOSD.

A bioengineered anti-VEGF protein with high affinity and high concentration for intravitreal treatment of wet age-related macular degeneration.

Intravitreal (IVT) injection of anti-vascular endothelial growth factor (anti-VEGF) has greatly improved the treatment of many retinal disorders, including wet age-related macular degeneration (wAMD), which is the third leading cause of blindness. However, frequent injections can be difficult for patients and may lead to various risks such as elevated intraocular pressure, infection, and retinal detachment. To address this issue, researchers have found that IVT injection of anti-VEGF proteins at their maximally viable concentration and dose can be an effective strategy. However, the intrinsic protein structure can limit the maximum concentration due to stability and solution viscosity. To overcome this challenge, we developed a novel anti-VEGF protein called nanoFc by fusing anti-VEGF nanobodies with a crystallizable fragment (Fc). NanoFc has demonstrated high binding affinity to VEGF165 through multivalency and potent bioactivity in various bioassays. Furthermore, nanoFc maintains satisfactory chemical and physical stability at 4°C over 1 month and is easily injectable at concentrations up to 200 mg/mL due to its unique architecture that yields a smaller shape factor. The design of nanoFc offers a bioengineering strategy to ensure both strong anti-VEGF binding affinity and high protein concentration, with the goal of reducing the frequency of IV injections.

Association of the triglyceride-glucose index with all-cause and cardiovascular mortality in patients with cardiometabolic syndrome: a national cohort study.

OBJECTIVE: This study aimed to evaluate the association of triglyceride-glucose (TyG) index with all-cause and cardiovascular mortality risk among patients with cardiometabolic syndrome (CMS). METHODS: We performed a cohort study of 5754 individuals with CMS from the 2001-2018 National Health and Nutrition Examination Survey. The TyG index was calculated as Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Multivariate Cox proportional hazards regression models assessed the associations between TyG index and mortality . Non-linear correlations and threshold effects were explored using restricted cubic splines and a two-piecewise Cox proportional hazards model. RESULTS: Over a median follow-up of 107 months, 1201 all-cause deaths occurred, including 398 cardiovascular disease-related deaths. The multivariate Cox proportional hazards regression model showed a positive association between the TyG index and all-cause and cardiovascular mortality. Each one-unit increase in the TyG index was associated with a 16% risk increase in all-cause mortality (HR: 1.16, 95% CI 1.03, 1.31, P = 0.017) and a 39% risk increase in cardiovascular mortality (HR: 1.39, 95% CI 1.14, 1.71, P = 0.001) after adjusting for confounders. The restricted cubic splines revealed a U-shaped association between the TyG index and all-cause (P for nonlinear < 0.001) and cardiovascular mortality (P for nonlinear = 0.044), identifying threshold values (all-cause mortality: 9.104; cardiovascular mortality: 8.758). A TyG index below these thresholds displayed a negative association with all-cause mortality (HR: 0.58, 95% CI 0.38, 0.90, P = 0.015) but not with cardiovascular mortality (HR: 0.39, 95% CI 0.12, 1.27, P = 0.119). Conversely, a TyG index exceeding these thresholds was positively associated with all-cause and cardiovascular mortality (HR: 1.35, 95% CI 1.17, 1.55, P < 0.001; HR: 1.54, 95% CI 1.25, 1.90, P < 0.001, respectively). Notably, a higher TyG index (≥ threshold values) was significantly associated with increased mortality only among individuals aged under 55 compared to those with a lower TyG index (< threshold values). CONCLUSIONS: The TyG index demonstrated a U-shaped correlation with all-cause and cardiovascular mortality in individuals with CMS. The thresholds of 9.104 and 8.758 for all-cause and cardiovascular mortality, respectively, may be used as intervention targets to reduce the risk of premature death and cardiovascular disease.

Predicting the rapid progression of mild cognitive impairment by intestinal flora and blood indicators through machine learning method.

INTRODUCTION: The aim of the work was to establish a prediction model of mild cognitive impairment (MCI) progression based on intestinal flora by machine learning method. METHOD: A total of 1013 patients were recruited, in which 87 patients with MCI finished a two-year follow-up. To establish a prediction model, 61 patients were randomly divided into a training set and 26 patients were divided into a testing set. A total of 121 features including demographic characteristics, hematological indicators, and intestinal flora abundance were analyzed. RESULTS: Of the 87 patients who finished a two-year follow-up, 44 presented rapid progression. Model 1 was established based on 121 features with the accuracy 85%, sensitivity 85%, and specificity 83%. Model 2 was based on the first fifteen features of Model 1, (triglyceride, uric acid, alanine transaminase, F-Clostridiaceae, G-Megamonas, S-Megamonas, G-Shigella, G-Shigella, S-Shigella, average hemoglobin concentration, G-Alistipes, S-Collinsella, median cell count, average hemoglobin volume, Low-density lipoprotein), with the accuracy 97%, sensitivity 92%, and specificity 100%. Model 3 was based on the first ten features of Model 1, with the accuracy 97%, sensitivity 86%, and specificity 100%. Other models based on the demographic characteristics, hematological indicators, or intestinal flora abundance features presented lower sensitivity and specificity. CONCLUSION:  The 15 features (including intestinal flora abundance) could establish an effective model for predicting rapid MCI progression.

Central blockage of sympathetic nerves inhibits the abnormal vital signs and disturbance of the gut microbiota caused by continuous light exposure.

Background: Continuous light exposure increases sympathetic excitation in rats, leading to hypertension, left ventricular hypertrophy, and fibrosis. This study was aimed to investigate whether continuous light exposure causes destabilization of vital signs and gut microbiota (GM) in Sprague Dawley (SD) rats and whether clonidine hydrochloride (CH), a central sympathetic depressant drug, could prevent these changes. Methods: Eight-week-old male SD rats were divided into three groups with different interventions for 14 weeks: control group (CG), 2-mL pure water gavaged daily while on a normal 12-h light/dark cycle; continuous illumination group (CI), 2-mL pure water gavaged daily while receiving continuous exposure to light (300 lx); and drug administration group (DA), CH (10 µg/kg) gavaged daily while receiving continuous exposure to light (300 lx). Results: The results showed that blood pressure, heart rate, and body weight were significantly higher in the CI group than in the CG and DA groups (P < 0.05). Moreover, the Shannon index was higher in the DA group than in the CI group (P = 0.012). The beta diversity index in the CG group was significantly higher in the CI group (P = 0.039). The pairwise comparison results of the linear discriminant analysis effect size showed that Oscillospirales were enriched in the DA group, whereas the Prevotellaceae lineage (family level) > Prevotella (genus level) > Prevotellaceae_bacterium (species level) were enriched in the CI group. The Muribaculaceae family was more abundant in the CG group than in the CI group. Conclusion: Sympathetic nerve inhibition restored the abnormal vital signs and GM changes under continuous light exposure.

The Epidemiological Characteristics of Pulmonary Tuberculosis in Ganxian District, Ganzhou City, Jiangxi Province, China from 2011 to 2021.

Objective: This study aims to understand the characteristics and current situation of pulmonary tuberculosis (PTB) data of Ganxian District, Ganzhou City, Jiangxi Province, China from 2011 to 2021, and to provide data support and a scientific basis for the prevention and control of PTB in the county. Methods: The data were collected from the National Notifiable Disease Reporting System (NNDRS), which included information reported such as the gender, ethnicity, age, occupation, and diagnostic classification of reported PTB cases. Descriptive statistics were used to describe the characteristics of PTB patients. The SPSS 21.0 data analysis tool was used to analyze patient data, investigating the epidemiological characteristics of PTB in the region. Results: There were 4962 PTB cases reported from 2011 to 2021 in Ganxian District, with a decreasing trend. In terms of months, March and September had the highest cumulative number of reported cases, with 511 cases (10.3%) and 515 cases (10.4%), respectively. In terms of reported cases by area, Meilin Town and Jiangkou Town had the highest number, with 603 and 519 cases, respectively. In terms of gender, there were more male patients (3743 cases) than female patients (1,219 cases) , which had statistically significant differences (χ2 = 27.0, P < .001). The majority of cases were secondary PTB, with farmers being the most affected (a total of 4287 cases) compared to other occupations. In addition, most patients were aged between 40 and 70 years (a total of 2790 cases). Regarding treatment outcomes, out of 4,962 PTB patients, 2088 were cured, with a cure rate of 42.1%. Conclusion: Based on the characteristics of PTB in the area, future prevention and control work should focus on males, farmers, young students, and the elderly, while also focusing on the prevention and control of secondary PTB.

[Expression and characterization of mesophilic GH1 ß-glucosidase CdBglA from acidophilic Cuniculiplasma divulgatum].

ß-glucosidase has important applications in food, pharmaceutics, biomass conversion and other fields, exploring ß-glucosidase with strong adaptability and excellent properties thus has received extensive interest. In this study, a novel glucosidase from the GH1 family derived from Cuniculiplasma divulgatum was cloned, expressed, and characterized, aiming to find a better ß-glucosidase. The amino acid sequences of GH1 family glucosidase derived from C. divulgatum were obtained from the NCBI database, and a recombinant plasmid pET-30a(+)-CdBglA was constructed. The recombinant protein was induced to express in Escherichia coli BL21(DE3). The enzymatic properties of the purified CdBglA were studied. The molecular weight of the recombinant CdBglA was 56.0 kDa. The optimum pH and temperature were 5.5 and 55 ℃, respectively. The enzyme showed good pH stability, 92.33% of the initial activity could be retained when treated under pH 5.5-11.0 for 1 h. When pNPG was used as a substrate, the kinetic parameters Km, Vmax and Kcat/Km were 0.81 mmol, 291.99 µmol/(mg·min), and 387.50 s-1 mmol-1, respectively. 90.33% of the initial enzyme activity could be retained when CdBglA was placed with various heavy metal ions at a final concentration of 5 mmol/L. The enzyme activity was increased by 28.67% under 15% ethanol solution, remained unchanged under 20% ethanol, and 43.68% of the enzyme activity could still be retained under 30% ethanol. The enzyme has an obvious activation effect at 0-1.5 mol/L NaCl and can tolerate 0.8 mol/L glucose. In conclusion, CdBglA is an acidic and mesophilic enzyme with broad pH stability and strong tolerance to most metal ions, organic solvents, NaCl and glucose. These characteristics may facilitate future theoretical research and industrial production.

Dysregulation of Ruminococcaceae and Megamonas could be predictive markers for rapid progression of mild cognitive impairment.

BACKGROUND: Intestinal flora dysregulation may affect the development of Alzheimer's disease (AD). However, the correlation between intestinal flora and rapid progression of mild cognitive impairment (MCI) is rarely reported. Our aim was to investigate the features of the intestinal flora in patients with rapidly progressive MCI. METHOD: A total of 1013 participants were screened, in which 87 patients with MCI were followed up for two years. At the baseline time point, fecal samples of the patients were sequenced via the microbial diversity high-throughput 16 s-rDNA. RESULTS: After a two-year follow-up, 30 patients with MCI presented rapidly progressive cognitive impairment, whereas the 57 patients remained unprogressive. Analyses of their fecal samples showed that the abundance of 11 intestinal microflora were significantly different between the two groups at the baseline time point. Further analyses revealed that the decrease of Ruminococcaceae abundance and the increase of Megamonas abundance were significantly correlated with the progression of MCI. Also, the decreased Ruminococcaceae was independently associated with several factors such as P-tau181, and the increased Megamonas was independently associated with diabetes, low-density lipoprotein, median cell count. CONCLUSION: The decrease of Ruminococcaceae and the increase of Megamonas could act as predictive markers for the rapidly progressive MCI.

Palliative care needs and specialist services post stroke: national population-based study.

OBJECTIVES: (1) To compare palliative care needs of patients admitted primarily with stroke and (2) to determine how the care needs of these patients affect their use of different types of specialist palliative care services. METHODS: Observational study based on point-of-care data from the Australian Palliative Care Outcomes Collaboration. Multivariate logistic regression models were used to explore the association between patients' palliative care needs and use of community versus inpatient specialist palliative care services. RESULTS: The majority of patients who had a stroke in this study population had mild or no symptom distress, but experienced a high degree of functional impairment and needed substantial help with basic tasks of daily living. A lower Australia-modified Karnofsky Performance Status score (OR=1.82, 95% CI 1.06 to 3.13) and occurrence of an 'unstable' palliative care phase (OR=28.34, 95% CI 9.03 to 88.94) were associated with use of inpatient versus community palliative care, but otherwise, no clear association was observed between the majority of symptoms and use of different care services. CONCLUSIONS: Many people with stroke could potentially have been cared for and could have experienced the terminal phases of their condition in a community setting if more community support services were available for their families.

S1PR1 attenuates pulmonary fibrosis by inhibiting EndMT and improving endothelial barrier function.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic fatal disease of unknown etiology. Its pathological manifestations include excessive proliferation and activation of fibroblasts and deposition of extracellular matrix. Endothelial cell-mesenchymal transformation (EndMT), a novel mechanism that generates fibroblast during IPF, is responsible for fibroblast-like phenotypic changes and activation of fibroblasts into hypersecretory cells. However, the exact mechanism behind EndMT-derived fibroblasts and activation is uncertain. Here, we investigated the role of sphingosine 1-phosphate receptor 1 (S1PR1) in EndMT-driven pulmonary fibrosis. METHODS: We treated C57BL/6 mice with bleomycin (BLM) in vivo and pulmonary microvascular endothelial cells with TGF-ß1 in vitro. Western blot, flow cytometry, and immunofluorescence were used to detect the expression of S1PR1 in endothelial cells. To evaluate the effect of S1PR1 on EndMT and endothelial barrier and its role in lung fibrosis and related signaling pathways, S1PR1 agonist and antagonist were used in vitro and in vivo. RESULTS: Endothelial S1PR1 protein expression was downregulated in both in vitro and in vivo models of pulmonary fibrosis induced by TGF-ß1 and BLM, respectively. Downregulation of S1PR1 resulted in EndMT, indicated by decreased expression of endothelial markers CD31 and VE-cadherin, increased expression of mesenchymal markers α-SMA and nuclear transcription factor Snail, and disruption of the endothelial barrier. Further mechanistic studies found that stimulation of S1PR1 inhibited TGF-ß1-mediated activation of the Smad2/3 and RhoA/ROCK1 pathways. Moreover, stimulation of S1PR1 attenuated Smad2/3 and RhoA/ROCK1 pathway-mediated damage to endothelial barrier function. CONCLUSIONS: Endothelial S1PR1 provides protection against pulmonary fibrosis by inhibiting EndMT and attenuating endothelial barrier damage. Accordingly, S1PR1 may be a potential therapeutic target in progressive IPF.

S1PR2/Wnt3a/RhoA/ROCK1/ß-catenin signaling pathway promotes diabetic nephropathy by inducting endothelial mesenchymal transition and impairing endothelial barrier function.

AIMS: Hyperglycemia and hyperlipidemia are key factors in the pathogenesis of diabetic nephropathy (DN), and renal fibrosis is the most common pathway leading to the disease. Endothelial mesenchymal transition (EndMT) is a crucial mechanism for the production of myofibroblasts, and impaired endothelial barrier function is one of the mechanisms for the generation of microalbuminuria in DN. However, the specific mechanisms behind these are not yet clear. MAIN METHODS: Protein expression was detected by immunofluorescence, immunohistochemistry and Western blot. Knocking down or pharmacological inhibition of S1PR2 were used to inhibit Wnt3a, RhoA, ROCK1, ß-catenin, and Snail signaling. Changes in cell function were analyzed by CCK-8 method, cell scratching assay, FITC-dextran permeability assay, and Evans blue staining. KEY FINDINGS: Consistent with increased gene expression of S1PR2 in DN patients and mice with kidney fibrosis disease, S1PR2 expression was significantly increased in glomerular endothelial cells of DN mice and HUVEC cells treated with glucolipids. Knocking down or pharmacological inhibition of S1PR2 significantly decreased the expression of Wnt3a, RhoA, ROCK1, and ß-catenin in endothelial cells. Furthermore, inhibition of S1PR2 in vivo reversed EndMT and endothelial barrier dysfunction in glomerular endothelial cells. Inhibition of S1PR2 and ROCK1 in vitro also reversed EndMT and endothelial barrier dysfunction in endothelial cells. SIGNIFICANCE: Our results suggest that the S1PR2/Wnt3a/RhoA/ROCK1/ß-catenin signaling pathway is involved in the pathogenesis of DN by inducing EndMT and endothelial barrier dysfunction.

Machine-learning-based analysis of the sensitivity and specificity on lipid-lowering effect of one-month-administered statins.

Few predictive studies have been reported on the efficacy of atorvastatin in reducing lipoprotein cholesterol to be qualified after 1-month course of treatment in different individuals. A total of 14,180 community-based residents aged ≥ 65 received health checkup, 1013 of whom had low-density lipoprotein (LDL) higher than 2.6mmol/L so that they were put on 1-month course of treatment with atorvastatin. At its completion, lipoprotein cholesterol was measured again. With < 2.6 mmol/L considered as the treatment standard, 411 individuals were judged as the qualified group, and 602, and as the unqualified group. The basic sociodemographic features covered 57 items. The data were randomly divided into train sets and test ones. The recursive random-forest algorithm was applied to predicting the patients response to atorvastatin, the recursive feature elimination method, to screening all the physical indicators. The overall accuracy, sensitivity and specificity were calculated, respectively, and so were the receiver operator characteristic curve and the area under the curve of the test set. In the prediction model on the efficacy of 1-month treatment of statins for LDL, the sensitivity, 86.86%; and the specificity, 94.83%. In the prediction model on the efficacy of the same treatment for triglyceride, the sensitivity, 71.21%; and the specificity, 73.46%. As to the prediction of total cholesterol, the sensitivity, 94.38%; and the specificity, 96.55%. And in the case of high-density lipoprotein (HDL), the sensitivity, 84.86%; and the specificity, 100%. recursive feature elimination analysis showed that total cholesterol was the most important feature of atorvastatin efficacy of reducing LDL; that HDL was the most important one of its efficacies of reducing triglycerides; that LDL was the most important one of its efficacies of reducing total cholesterol; and that triglyceride was the most important one of its efficacies of reducing HDL. Random-forest can help predict whether atorvastatin efficacy of reducing lipoprotein cholesterol to be qualified after 1-month course of treatment in different individuals.

Case report: Complex paraneoplastic syndromes in thymoma with nephrotic syndrome, cutaneous amyloidosis, myasthenia gravis, and Morvan's syndrome.

Background: Apart from myasthenia gravis (MG), thymoma is associated with a wide spectrum of autoimmune paraneoplastic syndromes (PNSs). Here, we report on a rare case presenting with four different PNSs, namely, MG, membranous nephropathy, cutaneous amyloidosis, and Morvan's syndrome associated with thymoma. Case presentation: A middle-aged man was frequently hospitalized because of nephrotic syndrome (stage I membranous nephropathy), cutaneous amyloidosis, and MG with acetylcholine receptor (AChR) antibody and titin antibody positivity. Chest CT showed a thymic mass in the left anterior mediastinum, and he received intravenous immunoglobulin (IVIG), methylprednisolone pulse therapy, thoracoscopic thymoma resection, and radiotherapy. Postoperative pathological examination revealed a type B2 thymoma. During the perioperative stage, his electrocardiogram (ECG) showed myocardial infarction-like ECG changes; however, his levels of cardiac enzymes and troponin were normal, and he had no symptoms of precardiac discomfort. Six months after thymectomy, his nephrotic syndrome and MG symptoms were relieved; however, he presented with typical manifestations of Morvan's syndrome, including neuromyotonia, severe insomnia, abnormal ECG activity, and antibodies against leucine-rich glioma-inactivated 1 (LGI1) and γ-amino-butyric acid-B receptor (GABABR). His symptoms did not improve after repeated IVIG and steroid therapies. Finally, he received low-dose rituximab, and his symptoms gradually resolved. Conclusion: This case serves to remind us that apart from MG, thymoma is also associated with other autoimmune PNSs such as membranous nephropathy, cutaneous amyloidosis, and Morvan's syndrome. Autoimmune PNSs can present concurrently with or after surgical or medical therapy for thymoma. For Morvan's syndrome post-thymectomy with LGI1 antibody positivity, B-cell depletion therapy such as intravenous rituximab is an effective treatment.

Single-cell transcriptomics reveals cell type-specific immune regulation associated with anti-NMDA receptor encephalitis in humans.

Introduction: Anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE) is a rare autoimmune disease, and the peripheral immune characteristics associated with anti-NMDARE antibodies remain unclear. Methods: Herein, we characterized peripheral blood mononuclear cells from patients with anti-NMDARE and healthy individuals by single-cell RNA sequencing (scRNA-seq). Results: The transcriptional profiles of 129,217 cells were assessed, and 21 major cell clusters were identified. B-cell activation and differentiation, plasma cell expansion, and excessive inflammatory responses in innate immunity were all identified. Patients with anti-NMDARE showed higher expression levels of CXCL8, IL1B, IL6, TNF, TNFSF13, TNFSF13B, and NLRP3. We observed that anti-NMDARE patients in the acute phase expressed high levels of DC_CCR7 in human myeloid cells. Moreover, we observed that anti-NMDARE effects include oligoclonal expansions in response to immunizing agents. Strong humoral immunity and positive regulation of lymphocyte activation were observed in acute stage anti-NMDARE patients. Discussion: This high-dimensional single-cell profiling of the peripheral immune microenvironment suggests that potential mechanisms are involved in the pathogenesis and recovery of anti-NMDAREs.

Cost-effectiveness analysis of sintilimab plus pemetrexed and platinum versus chemotherapy alone as first-line treatment in metastatic non-squamous non-small cell lung cancer in China.

OBJECTIVE: In frst-line treatment of advanced or metastatic nonsquamous non-small-cell lung cancer (NSCLC), the ORIENT-11 study demonstrated a signifcant progression-free survival and overall survival for sintilimab plus chemotherapy in comparison with chemotherapy alone. But the cost-effectiveness of the two treatment schemes is unclear in China. The objective of the current study was to evaluate the cost efectiveness of sintilimab plus chemotherapy versus Platinum-based chemotherapy for locally advanced or metastatic squamous NSCLC in China. METHODS: We performed an economic evaluation from the perspective of the Chinese healthcare system using a partitioned survival model with three mutually exclusive health states: progression free, post-progression, and death. The circulation cycle of the model was 3 weeks and the study time limit was 10 years. Efficacy data were obtained from the ORIENT-11 clinical trial. Cost and utility values were derived from published studies and online price databases. The primary outcomes of the model were quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). One-way sensitivity analysis and probability sensitivity analysis were used to verify the robustness of the base-case analysis results. RESULTS: Sintilimab plus chemotherapy provided an additional 0.6 QALYs. The total cost per patient was CNY¥413,273.16 for sintilimab plus chemotherapy and CNY¥280,695.23 for Platinum-based chemotherapy. The ICER for sintilimab plus chemotherapy was CNY¥220,963.22/QALY. Sensitivity analyses found the results to be most sensitive to the cost of pemetrexed and utilities of PF state. In the probabilistic sensitivity analysis, sintilimab was cost-efective in 78.6% of the simulations, assuming a willingness-to-pay threshold (WTP) of CNY¥242,928 per QALY. CONCLUSION: Compared with chemotherapy alone, the sintilimab plus chemotherapy is likely to be a cost-effective option as the first-line treatment for locally advanced or metastatic nonsquamous NSCLC in China.

Stimulus responsive microcapsules and their aromatic applications.

Fragrances and essential oils are promising for a wide range of applications due to their pleasant odors and diverse effects. However, direct addition to consumer products has the disadvantages of short retention time and easy deterioration of odor. At the same time, releasing a large amount of odor in a short time may be an unpleasant experience, which severely limits the practical application of aromatic substances. Microencapsulation perfectly solves these problems. Stimuli-responsive microcapsules, which combine environmental stimulation with microencapsulation, can not only effectively prevent the rapid decomposition and evaporation of aroma components, but also realize the "on-off" intelligent release of aroma substances to environmental changes, which have great promise in the field of fragrances. In this review, the application of stimuli-responsive microcapsules in fragrances is highlighted. Firstly, various encapsulation materials used to prepare stimuli-responsive aromatic microcapsules are described, mainly including some natural polymers, synthetic polymers, and inorganic materials. Subsequently, there is a detailed description of the common release mechanisms of stimuli-responsive aromatic microcapsules are described in detail. Finally, the application and future research directions are given for stimuli-responsive aromatic microcapsules in new textiles, food, paper, and leather.

Fibrinogen like protein-1 knockdown suppresses the proliferation and metastasis of TU-686 cells and sensitizes laryngeal cancer to LAG-3 blockade.

OBJECTIVE: To detect the expression of fibrinogen like protein-1 (FGL-1) in laryngeal cancer and evaluate its effect on tumor proliferation, metastasis, and antitumor immunity. METHODS: ELISA and immunohistochemistry were performed to detect FGL-1 expression in laryngeal cancer. The effects of FGL-1 knockdown on the proliferation, cell cycle progression, apoptosis, migration, and invasion of laryngeal cancer cells were evaluated by the CCK-8, colony formation, flow cytometry, Transwell migration, and western blot assays. We detected changes in tumorigenesis and drug response in vivo following FGL-1 knockdown as well as the effects of anti-LAG3 immunotherapy. Immunohistochemistry was performed to determine CD8 and LAG-3 expression in mouse tumor tissues. RESULTS: FGL-1 was highly expressed in the plasma and tumor tissues of laryngeal cancer patients. FGL-1 knockdown suppressed the proliferation of TU-686 cells and inhibited the migration and invasion of laryngeal cancer by blocking epithelial-to-mesenchymal transition. Moreover, silencing FGL-1 inhibited tumorigenicity in vivo and synergized with anti-LAG3 immunotherapy. CONCLUSIONS: We confirmed the high expression of FGL-1 in laryngeal cancer and identified FGL-1 as a potential marker for immunotherapy in laryngeal cancer.