Advances in Metabolic Regulation of Macrophage Polarization State.

Macrophages are significant immune-related cells that are essential for tissue growth, homeostasis maintenance, pathogen resistance, and damage healing. The studies on the metabolic control of macrophage polarization state in recent years and the influence of polarization status on the development and incidence of associated disorders are expounded upon in this article. Firstly, we reviewed the origin and classification of macrophages, with particular attention paid to how the tricarboxylic acid cycle and the three primary metabolites affect macrophage polarization. The primary metabolic hub that controls macrophage polarization is the tricarboxylic acid cycle. Finally, we reviewed the polarization state of macrophages influences the onset and progression of cancers, inflammatory disorders, and other illnesses.

Development and Validation of Prediction Models for Exacerbation, Frequent Exacerbations and Severe Exacerbations of Chronic Obstructive Pulmonary Disease: A Registry Study in North China.

In COPD patients, exacerbation has a detrimental influence on the quality of life, disease progression and socioeconomic burden. This study aimed to develop and validate models to predict exacerbation, frequent exacerbations and severe exacerbations in COPD patients. We conducted an observational prospective multicenter study. Clinical data of all outpatients with stable COPD were collected from Beijing Chaoyang Hospital and Beijing Renhe Hospital between January 2018 and December 2019. Patients were followed up for 1 year. The data from Chaoyang Hospital was used for modeling dataset, and that of Renhe Hospital was used for external validation dataset. The final dataset included 456 patients, with 326 patients as the model group and 130 patients as the validation group. Using LABA + ICS, frequent exacerbations in the past year and CAT score were independent risk factors for exacerbation in the next year (OR = 2.307, 2.722 and 1.147), and FVC %pred as a protective factor (OR = 0.975). Combined with chronic heart failure, frequent exacerbations in the past year, blood EOS counts and CAT score were independent risk factors for frequent exacerbations in the next year (OR = 4.818, 2.602, 1.015 and 1.342). Using LABA + ICS, combined with chronic heart failure, frequent exacerbations in the past year and CAT score were independent risk factors for severe exacerbations in the next year (OR = 1.950, 3.135, 2.980 and 1.133). Based on these prognostic models, nomograms were generated. The prediction models were simple and useful tools for predicting the risk of exacerbation, frequent exacerbations and severe exacerbations of COPD patients in North China.

Characterising baseflow signature variability in the Yellow River Basin.

Baseflow is pivotal in maintaining catchment ecological health and improving sustainable economic development. The Yellow River Basin (YRB) is northern China's most important water supplier. However, it faces water shortage due to synergistic effects between natural conditions and anthropogenic activities. Investigating baseflow characteristics quantitively is, therefore, beneficial to promoting the sustainable development of the YRB. In this study, daily ensemble means baseflow data derived from four revised baseflow separation algorithms (i.e., the United Kingdom Institute of Hydrology (UKIH), Lyne-Hollick, Chapman-Maxwell, and Eckhardt methods) - was obtained from 2001 to 2020. Thirteen baseflow dynamics signatures were extracted to investigate baseflow spatiotemporal variations and their determinants across the YRB. The main findings were: (1) There were significant spatial distribution patterns of baseflow signatures, and most signatures had higher values in upstream and downstream reaches than in the middle reaches. There were also mixing patterns with higher values in middle and downstream reaches simultaneously. (2) The magnitude of temporal variation in baseflow signatures was most strongly correlated with catchment terrain (r = -0.4), vegetation growth (r > 0.3), and cropland coverage (r > 0.4). (3) There was a strong synergistic effect of multiple factors (e.g., soil textures, precipitation and vegetation conditions) on baseflow signature values. This study provided a heuristic evaluation of baseflow characteristics in the YRB, contributing to water resources management in the YRB and similar catchments.

Changes in the SO2 Level and PM2.5 Components in Shanghai Driven by Implementing the Ship Emission Control Policy.

This study aims to understand the effect of the Domestic Emission Control Area (DECA) policy on ambient SO2 and particle components in Shanghai. Online single particle analysis and SO2 measurements from 2015 to 2017 were compared to analyze the long-term variations before and after the DECA policy. Our study showed that there was a significant decrease in SO2 by 27-55% after the implementation of the DECA policy. The number fraction of ship-emitted particles increased along with the increase in ship traffic activity, but the particles tended to contain lower-vanadium content. The elemental carbon component decreased, while the organic carbon components increased after switching oil. One thousand and ninety four ship fuel oil samples were collected. The oil sample analysis confirmed the ambient particle results; sulfur content decreased in domestic ship heavy fuel oils from 2013 to 2018; in the low sulfur fuel oils used after the DECA policy, vanadium was still highly correlated with sulfur as it was in high-sulfur fuels. Our results suggested that heavy fuel oil is still a major part of the low-sulfur ship oils in use. The multiple-component control including organic pollutants regarding low sulfur fuel oils may be necessary for preventing air pollution from ship emissions.

Structure and Anti-Tumor Activities of Exopolysaccharides from Alternaria mali Roberts.

In this study, an extracellular polysaccharide from Alternaria mali Roberts (AMEP) was extracted, and its structure was characterized, in addition to its antitumor activity in vitro. Neutral polysaccharide AMEP-1 and anionic polysaccharide AMEP-2 were isolated from AMEP, and their monosaccharide compositions consisted of mannose (Man), glucose (Glc), and galactose (Gal) but at different ratios. The linking mode of both AMEP-1 and AMEP-2 is Manp-(1→4) and Glcp-(1→6), and the branched chains are connected to the main chain through O-6. AMEP-2 inhibited the proliferation of BGC-823 cells in a time- and concentration-dependent manner. AMEP-2 also induced the apoptosis of BGC-823 cells, and showed anti-tumor effects by inducing cell cycle arrest in the S phase, reactive oxygen species production, and mitochondrial membrane potential reduction in BGC-823 cells. Therefore, AMEP-2 shows potential for further development as a novel anti-tumor agent.

Effects of partial replacement of fish meal by yeast hydrolysate on antioxidant capability, intestinal morphology, and inflammation-related gene expression of juvenile Jian carp (Cyprinus carpio var. Jian).

This study aimed to evaluate the effects of fish meal (FM) replacement by yeast hydrolysate (YH) on liver antioxidant capability, intestinal morphology, and inflammation-related genes of juvenile Jian carp (Cyprinus carpio var. Jian). A total of 600 fish (average initial weight 19.44 ± 0.06 g) were randomly selected and divided into five groups. Five isonitrogenous and isocaloric diets replacing FM by YH 0% (YH0), 1% (YH1), 3% (YH3), 5% (YH5), and 7% (YH7) were formulated. Each diet was tested in four replicates for 10 weeks. The results have shown that, compared to the control group (YH0), liver total superoxide dismutase (t-SOD), catalase (CAT), glutathione peroxidase (GPX), and glutathione (GSH) activities of fish fed YH1 and YH3 diets were significantly higher (P < 0.05). Liver malondialdehyde (MDA) concentration significantly increased as supplementation levels of YH increased from 1 to 7% (P < 0.05). Moreover, intestinal microvillus length of juvenile Jian carp fed YH diets were significantly higher than that of fish fed the control diet (P < 0.05). In proximal intestine, the relative expression levels of inflammation-related genes (ALP, IL-1ß, and TNF-α) in YH7 were significantly higher than that in the control group (P < 0.05). However, in midintestine, the expression levels of these genes in YH3 were significantly lower compared to the control group (P < 0.05). The results of this study indicated that dietary replacement of FM by 3%YH could improve antioxidant capability and intestinal microvillus morphology, as well as enhance the non-specific immunity of juvenile Jian carp.

Mangosteen ethanol extract alleviated the severity of collagen-induced arthritis in rats and produced synergistic effects with methotrexate.

CONTEXT: Garcinia mangostana Linn. (Guttiferae) pericarp is used as a traditional medicine in South Asia to treat inflammatory diseases. OBJECTIVE: This study investigates therapeutic effects of G. mangostana pericarp ethanol extract (MAN) on collagen-induced arthritis (CIA) and interactions with methotrexate in vivo. MATERIALS AND METHODS: Male Sprague-Dawley rats with CIA were treated with MAN (0.5 g/kg/day), methotrexate (0.5 mg/kg, bw) or combination of both for 36 days, respectively (n = 8/group). Another eight healthy and CIA rats served as normal and model control, respectively. Therapeutic effects were evaluated based on paw edema and arthritis score during the experiment and serological markers at the end of the study period. Histological and radiological examinations were used to assess joint destructions. The immune status was investigated by immunohistochemistry and flow cytometry. RESULTS: All treatments decreased the arthritis score and paw inflammation in CIA rats. Combination regimen significantly reduced anti-cyclic citrullinated peptide antibody in CIA rats to 85.83% (p < 0.05) and notably alleviated synovial hyperplasia and cartilage degradation in joints. Different from methotrexate, MAN significantly augmented CD25+ cells distribution (from 2.72 to 3.35%) and IL-10 secretion (from 202.4 to 241.2 pg/mL) in CIA rat blood. Meanwhile, MAN induced a greater IL-17 decrease and a FOXP3 increase in immune organs than MTX. Reduced TLR4 and IL-17 expression and elevated FOXP3 expression in joints also occurred under MAN treatment. CONCLUSIONS: MAN protected joints from destruction in CIA rats and exerted synergistic effects with methotrexate by improving immune microenvironment. The combination regimen could bring additional benefits to rheumatoid arthritis patients.

Folate-decorated and NIR-activated nanoparticles based on platinum(IV) prodrugs for targeted therapy of ovarian cancer.

Platinum-based drugs are used to treat a variety of cancers but have many side effects such as nephrotoxicity and neurotoxicity. A folate-decorated nanoparticles system with a good drug payload can selectively deliver drugs into folate receptor (FR)-overexpressing cancer cells to prevent the shortcomings of platinum-based chemotherapy. Here, folate-decorated and near-infrared (NIR) laser-activated nanoparticles (abbreviated as PtIV-FINPs) were prepared via ultrasonic self-assembling of platinum(IV) prodrug c,c,t-Pt(NH3)2Cl2(OOCCH2CH2COOH)2, folic acid (FA)-functionalized lipid DSPE-PEG-FA and NIR fluorescent dye indocyanine green (ICG). The obtained PtIV-FINPs had almost spherical shape with a mean diameter about 100 nm. In vitro cellular uptake, cytotoxicity assays revealed that upon NIR irradiation, PtIV-FINPs further enhanced cellular uptake and generated higher cytotoxicity against human ovarian carcinoma SKOV3 cells than non-targeted or non-NIR activated nanoparticles. Thus, the multifunctional nanoparticles have potential to be developed as an attractive drug delivery system for effective chemotherapy against FR-overexpressing cells.

[Combination of triptolide with sodium cantharidinate synergistically enhances apoptosis on hepatoma cell line 7721].

OBJECTIVE: To determine the combined cytotoxic effect and the molecular basis of triptolide and sodium cantharidinate on hepatoma cell line 7721.
 METHODS: After treating the hepatoma cell line 7721 with triptolide(9, 18, or 36 µg/mL) and/or sodium cantharidinate (2, 5, or 10 µg/mL), cell viability assay and apoptosis were examined by MTT and flocytometry, respectively. The protein levels of caspase 3 and nuclear factor κB were analyzed by Western blot.
 RESULTS: Viability of hepatoma cell line 7721 was inhibited by either the therapy of triptolide and/or sodium cantharidinate (P<0.05) in a time- and dose-dependent manner. The combined effects of both drugs were better than those of the single drug (P<0.05). The combined therapy down-regulated the expression of NF-κB p65 (P<0.05) while up-regulated the expression of caspase-3 (P<0.05).
 CONCLUSION: Triptolide and sodium cantharidinate exert a synergistic toxic effect on hepatoma cell line 7721, which is related to increasing capase-3 activity and suppression of NF- κB.

Letrozole ovulation induction: an effective option in endometrial preparation for frozen-thawed embryo transfer.

PURPOSE: To evaluate the clinical efficacy of letrozole on ovulation induction and hormone replacement therapy (HRT) during endometrial preparation for frozen-thawed embryo transfer (FET). METHODS: We analyzed totally 1,230 cycles of patients that underwent FET from October 2010 to September 2012. Seven hundred and thirteen cycles of patients with ovulation disorders that underwent FET were randomly assigned to two groups by case control study. 359 cycles received letrozole ovulation induction and 354 cycles received HRT during endometrial preparation for FET, respectively. In the corresponding period, 517 cycles of patients with normal ovulation in the natural cycle group for FET endometrial preparation served as controls. Reproduction-related clinical outcomes of patients in the three groups were compared. RESULTS: The embryo implantation rate of patients in letrozole group (30.4 %) was significantly higher than the HRT group (22.8 %, P < 0.05). The clinical pregnancy rate of patients in the letrozole group (53.2 %) was significantly higher than the HRT group (44.4 %, P < 0.05), while no significant difference was observed between the letrozole and natural cycle groups (51.3 %, P > 0.05). Estradiol levels on the day of human chorionic gonadotropin administration in the letrozole group were significantly lower than those in the natural cycle group (280.32 ± 125.39 pg/ml and 351.06 ± 123.03 pg/ml, respectively; P < 0.05). The live birth rate of patients in letrozole group (44.6 %) was significantly higher than the HRT group (32.5 %, P < 0.05), while abortion rate (12.0 %) was significantly lower than the HRT group (21.0 %, P < 0.05). There were no significant differences in number of mature follicles, endometrial thickness, duration of follicle growth between the letrozole and the natural cycle groups, and there were no significant differences in twin birth rate and ectopic pregnancy rate among the three groups (all P values >0.05). CONCLUSIONS: Ovulation induction with letrozole during endometrial preparation for FET has a higher rate of pregnancy success and a lower abortion rate than HRT. Letrozole treatment exhibits clinical progression and outcomes similar to those patients undergoing a natural cycle or normal ovulation cycle. Therefore, letrozole treatment may be an effective option in endometrial preparation for FET in patients with ovulation disorders or irregular menstruation.

Prone positioning does not improve outcomes of intubated patients with pneumocystis pneumonia and moderate-severe acute respiratory distress syndrome: a single-center, retrospective, observational, cohort study.

BACKGROUND: Pneumocystis pneumonia is an uncommon precipitant of acute respiratory distress syndrome and is associated with high mortality. Prone positioning ventilation has been proven to reduce mortality in patients with moderate-severe acute respiratory distress syndrome. We investigated the effect of prone positioning on oxygenation and mortality in intubated patients with pneumocystis pneumonia comorbid with moderate-severe acute respiratory distress syndrome. METHODS: In this single-center, retrospective, observational, cohort study, eligible patients were enrolled at West China Hospital of Sichuan University from January 1, 2017, to December 31, 2021. Data on demographics, clinical features, ventilation parameters, arterial blood gas, and outcomes were collected. Patients were assigned to the prone cohort or supine cohort according to whether they received prone positioning ventilation. The main outcome was 28-day mortality. FINDINGS: A total of 79 patients were included in the study. Sixty-three patients were enrolled in the prone cohort, and 16 patients were enrolled in the supine cohort. The 28-day mortality was 61.9% in the prone cohort and 68.8% in the supine cohort (P = 0.26), and 90-day mortality was 66.7% in the prone cohort and 68.8% in the supine cohort (P = 0.55). Patients in the supine cohort had fewer invasive mechanical ventilation days and more ventilator-free days. The incidence of complications was higher in the prone cohort than in the supine cohort. CONCLUSIONS: In patients with pneumocystis pneumonia and moderate-severe acute respiratory distress syndrome, prone positioning did not decrease 28-day or 90-day mortality. Trial registration ClinicalTrials.gov number, ChiCTR2200063889. Registered on 20 September 2022, https://www.chictr.org.cn/showproj.html?proj=174886 .

[Research progress of mesenchymal stem cell-derived exosomes in the treatment of inflammatory bowel disease].

Inflammatory bowel disease (IBD) is a chronic nonspecific inflammatory disease of the intestine, with unknown etiology and the incidence is increasing year by year. Traditional treatment has limited effect. Mesenchymal stem cell-derived exosomes (MSC-Exos) are a group of nano-sized extracellular vesicles. Their function is equivalent to that of mesenchymal stem cells (MSCs), with no tumorigenicity and high safety. They represent a novel cell-free therapy. It has been shown that MSC-Exos can improve IBD by effects including anti-inflammation, antioxidant stress, repairing intestinal mucosal barrier and immune regulation. However, their clinical application still faces some problems, such as the lack of standardized production technology, lack of specific IBD diagnostic molecules and anti-intestinal fibrosis.

Comparison of actual performance in humidification among different high-flow nasal cannula devices: a bench study.

Background: The physiological effects of HFNC devices are closely related to temperature and humidity. HFNC devices from different manufacturers may have varied performances. It is unclear whether there are differences in the humidification performance of different HFNC devices and the degree of differences. Methods: Four integrated HFNC devices (AIRVO 2, Fisher & Paykel Healthcare, Auckland, New Zealand; TNI softFlow 50, TNI Medical AG, Würzburg, Germany; HUMID-BH, RESPIRACARE, Shenyang, China; OH-70C, Micomme, Hunan, China) and a ventilator with an HFNC module (bellavista 1000, Imtmedical, Buchs, Switzerland) were evaluated using their matching circuits. The dew point temperature was set at 31, 34, and 37°C (set-DP). In MR850, it was set to non-invasive mode (34°C/-3°C) and invasive mode (40°C/-3°C), respectively. At each level of set-DP, the flow was set from 20 L/min up to its maximum set limit at a gradient of 5 L/min or 10 L/min. After stabilization, the dew point temperature, temperature, relative humidity, and flow rate of the delivered gas from the cannulas were recorded. Results: There were significant differences in actual-DP among these devices at any set-DP (p < 0.001). The actual-DP of OH-70C and TNI softFlow 50 was lower than set-DP, and the difference between the actual-DP and the set-DP of these two devices increased with the increase of set-DP. AIRVO 2, bellavista 1000 (MR850), and HUMID-BH can provide the nominal humidity at 37°C. The actual-DP increased with the increase of set-flow under each set-DP in AIRVO 2, TNI softFlow 50 and bellavista 1000 (MR850), but decreased when the set-flow was greater than 60 L/min. The actual-T of the delivered gas was higher than actual-DP in all devices and was higher than set-DP in AIRVO 2 and HUMID-BH. Conclusion: Set-flow, set-DP, and types of devices will affect the actual temperature and humidity of the delivered gas. AIRVO 2, bellavista 1000 (MR850), and HUMID-BH can provide the nominal humidity at 37°C and may be more suitable for tracheotomy patients. The flow rate over 60 L/min should be set with caution.

Arctigenin mitigates insulin resistance by modulating the IRS2/GLUT4 pathway via TLR4 in type 2 diabetes mellitus mice.

Arctigenin (AR), extracted from Arctium lappa L. (Burdock), is a folk herbal medicine used to treat diabetes. However, its mechanism of action has remained elusive. In this study, type 2 diabetes mellitus (T2DM) mice received AR orally for 10 weeks to evaluate its therapeutic effect based on changes in glucose and lipid metabolism, histological examination of target tissues, and liver immunohistochemistry. Furthermore, HepG2 insulin-resistant cells were established to verify the mechanism of AR against diabetes. The results showed that AR treatment reduced blood glucose and lipid levels, reversing liver as well as pancreas tissue damage in T2DM mice. AR reduced the levels of pro-inflammatory cytokines in the serum of T2DM mice, as well as those in insulin-resistant HepG2 cell supernatants, while increasing interleukin-10 (IL-10) levels. The levels of p-p65, phospho-c-Jun N-terminal kinase (p-JNK), induced nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were reduced in the liver tissue of T2DM mice, accompanied by an upregulation of glucose transporter 4 (GLUT4) and insulin receptor substrate 2 (IRS-2). In vitro studies further showed that AR downregulated toll-like receptor 4-mediated inflammation, while upregulating insulin pathway-related proteins and ultimately improving glucose uptake in insulin-resistant HepG2 cells. In conclusion, AR protected mice from insulin resistance, and its therapeutic effect was likely associated with inhibition of toll-like receptor 4 inflammatory signaling to reactivate IRS-2/GLUT4.

Gender differences in clinical characteristics of patients with non-cystic fibrosis bronchiectasis in different age groups in northern China.

INTRODUCTION: Patient gender has clinical and prognostic implications in non-cystic fibrosis bronchiectasis, yet the potential effect of gender on clinical characteristics of patients with non-cystic fibrosis bronchiectasis is still unclear. OBJECTIVES: This study aimed to investigate the gender differences in clinical characteristics of patients with bronchiectasis in different age groups in northern China. METHODS: A total of 777 patients diagnosed with bronchiectasis were retrospectively included in Beijing Chaoyang Hospital and divided into two groups by gender: the male group and the female group. Each group was then subdivided into two according to their age (≤65 and >65 years). Gender differences in clinical characteristics were compared in all patients with bronchiectasis in the two age groups, respectively. RESULTS: A total of 777 bronchiectasis patients were included. Of these patients, the prevalence of female non-smokers was substantially higher than that of male non-smokers (94.0% vs. 36.8%). There were gender differences in etiology of bronchiectasis, with more post-measles and connective tissue disease in females (p = 0.006 and 0.002 separately) and more chronic obstructive pulmonary disease (COPD) in males (p < 0.001). The male group had a significantly higher C-reactive protein (CRP) on admission (p = 0.03). Female patients showed a higher forced expiratory volume in 1 s as percentage of predicted volume (FEV1%pred) and forced vital capacity rate of 1 s (FEV1/FVC) (p < 0.001), lower partial pressure of carbon dioxide (PaCO2 ) (p = 0.04) and hospital costs (p = 0.02) than males, and a higher prevalence of infection with Pseudomonas aeruginosa in >65-year-old group (p = 0.019). CONCLUSIONS: There were many differences between male and female patients in smoking status, etiology, lung function, blood gas analysis, and hospital costs in all patients or different age groups.

[Clinical effect of letrozole on the ovulation induction in endometrial preparation for frozen-thawed embryo transfer].

OBJECTIVE: To evaluate the clinical effect of letrozole (LE) alone on the ovulation induction in endometrial preparation for frozen-thawed embryo transfer (FET). METHODS: Totally 253 FET cycles were analyzed by case control study from October 2010 to June 2011. We divided ovulation disorders or menstrual disorders divided into 2 groups: a LE group on ovulation induction cycle (n=85), and a hormone replacement therapy (HRT) cycle group (n=84). Meanwhile those who ovulated normally were included in a natural cycle group (n=84). Demographics and clinical parameters of reproductive correlation of all patients were observed among these groups. RESULTS: The average clinical pregnancy rate of the LE group was higher than that of HRT cycle group (54.1% vs 44.04%; P<0.05). The difference in the parameters such as patients' demographics and other clinical indexs had no statistical significance (P>0.05). The estradiol level on human chorionic gonadotrophin (HCG) administration day in the natural cycle group [(341.19±113.14) pg/mL] was higher than that of the LE group [(279.70±127.80) pg/mL] (P<0.05). There was no significant difference in the number of maturation follicles and endometrial thickness on the HCG administration day between the LE group and the natural cycle group (P>0.05). CONCLUSION: Ovulation induction with LE alone for endometrial preparation is superior to HRT cycle in FET and has similar clinical process and outcome to those of the natural cycle. It can be applied in endometrial preparation for FET effectively for those with anovulation or menstrual disorder.

Xanthones from Securidaca inappendiculata Hassk. attenuate collagen-induced arthritis in rats by inhibiting the nicotinamide phosphoribosyltransferase/glycolysis pathway and macrophage polarization.

Securidaca inappendiculata (SI) Hassk. is a traditional medicine used to treat rheumatoid arthritis. Recent studies have reported that macrophages are the primary regulators of joint homeostasis and their polarization is closely related to their metabolic mode. Here, we aimed to investigate the relationship between the joint protective effect of SI's xanthone-rich fraction (XRF) on collagen-induced arthritis (CIA) in rats and the nicotinamide phosphoribosyltransferase (NAMPT)-glycolysis-polarization axis of macrophages. CIA model rats were treated with oral XRF and therapeutic efficacy was assessed based on arthritis score, degree of paw swelling, histological examination, and immunohistochemical analysis. Serum levels of cytokines, cellular metabolite concentrations, and protein and mRNA expression were determined by enzyme-linked immunosorbent assay (ELISA), western blotting (WB), and quantitative real-time PCR (RT-qPCR), respectively. The effects of dihydroxy-3,4-dimethoxyxanthone (XAN), a representative SI-derived compound, on RAW264.7 macrophages was analyzed in vitro using confocal laser scanning and flow cytometry. We found that XRF treatment significantly alleviated disease severity in CIA model rats. Levels of pro-inflammatory cytokines in the serum and M1 markers in synovium were reduced after XRF treatment, accompanied by an increase in the levels of anti-inflammatory cytokines and M2 markers. Further, XRF significantly suppressed synovial glycolysis by regulating NAMPT. In vitro studies further showed that XAN induced repolarization of lipopolysaccharide (LPS)-induced RAW264.7 macrophages with M1-M2 phenotype. Moreover, XAN negatively regulated glycolysis in the LPS-induced RAW264.7 macrophages in correlation with changes in NAMPT expression. Overall, the findings of this study suggest that the joint protective effects of XRF are achieved by inhibiting the NAMPT/glycolysis pathway and thereby regulating macrophage polarization.

Development of a deep learning-based method to diagnose pulmonary ground-glass nodules by sequential computed tomography imaging.

BACKGROUND: Early identification of the malignant propensity of pulmonary ground-glass nodules (GGNs) can relieve the pressure from tracking lesions and personalized treatment adaptation. The purpose of this study was to develop a deep learning-based method using sequential computed tomography (CT) imaging for diagnosing pulmonary GGNs. METHODS: This diagnostic study retrospectively enrolled 762 patients with GGNs from West China Hospital of Sichuan University between July 2009 and March 2019. All patients underwent surgical resection and at least two consecutive time-point CT scans. We developed a deep learning-based method to identify GGNs using sequential CT imaging on a training set consisting of 1524 CT sections from 508 patients and then evaluated 256 patients in the testing set. Afterwards, an observer study was conducted to compare the diagnostic performance between the deep learning model and two trained radiologists in the testing set. We further performed stratified analysis to further relieve the impact of histological types, nodule size, time interval between two CTs, and the component of GGNs. Receiver operating characteristic (ROC) analysis was used to assess the performance of all models. RESULTS: The deep learning model that used integrated DL-features from initial and follow-up CT images yielded the best diagnostic performance, with an area under the curve of 0.841. The observer study showed that the accuracies for the deep learning model, junior radiologist, and senior radiologist were 77.17%, 66.89%, and 77.03%, respectively. Stratified analyses showed that the deep learning model and radiologists exhibited higher performance in the subgroup of nodule sizes larger than 10 mm. With a longer time interval between two CTs, the deep learning model yielded higher diagnostic accuracy, but no general rules were yielded for radiologists. Different densities of components did not affect the performance of the deep learning model. In contrast, the radiologists were affected by the nodule component. CONCLUSIONS: Deep learning can achieve diagnostic performance on par with or better than radiologists in identifying pulmonary GGNs.

Comparison of Actual Performance in the Flow and Fraction of Inspired O2 among Different High-Flow Nasal Cannula Devices: A Bench Study.

Background: High-flow nasal cannula (HFNC) oxygen therapy has been recommended for use in coronavirus disease 2019 (COVID-19) patients with acute respiratory failure and many other clinical conditions. HFNC devices produced by different manufacturers may have varied performance. Whether there is a difference in these devices and the extent of the differences in performance remain unknown. Methods: Four HFNC devices (AIRVO 2, TNI softFlow 50, HUMID-BH, and OH-70C) and a ventilator with an HFNC module (bellavista 1000) were evaluated. The flow was set at 20, 25, 30, 35, 40, 45, 50, 60, 70, and 80 L/min, and the FiO2 was set at 21%, 26%, 30%, 35%, 40%, 45%, 50%, 60%, 70%, 80%, and 90%. Then, one side of the cannulas was clipped to simulate the compression, bending, or blocking of the nasal cannulas. The flow and FiO2 of the delivered gas were recorded and compared among settings and devices. Results: The actual-flow and actual-FiO2 delivered by different settings and devices varied. AIRVO 2 had superior performance in flow and FiO2 accuracy. bellavista 1000 and OH-70C had good performance in the accuracy of actual-flows and actual-FiO2, respectively. bellavista 1000 and HUMID-BH had a larger flow range from 10 to 80 L/min, but only bellavista 1000 could provide a stable flow with an excessive resistance up to 60 L/min. TNI softFlow 50 had the best flow compensation and could provide sufficient flow with excessive resistance at 20-50 L/min. Conclusions: The variation in flow, FiO2 settings, and devices could influence the actual-flow and actual-FiO2 delivered. AIRVO 2 and OH-70C showed better FiO2 accuracy. TNI softFlow 50, bellavista 1000, and HUMID-BH could lower the risk of insufficient flow support due to accidental compression or blocking of the cannulas. In addition, ventilators with HFNC modules provided comparable flow and FiO2 and could be an alternative to standalone HFNC devices.

Hydrological projections in the upper reaches of the Yangtze River Basin from 2020 to 2050.

Understanding the impact of climate change on runoff is essential for effective water resource management and planning. In this study, the regional climate model (RCM) RegCM4.5 was used to dynamically downscale near-future climate projections from two global climate models to a 50-km horizontal resolution over the upper reaches of the Yangtze River (UYRB). Based on the bias-corrected climate projection results, the impacts of climate change on mid-twenty-first century precipitation and temperature in the UYRB were assessed. Then, through the coupling of a large-scale hydrological model with RegCM4.5, the impacts of climate change on river flows at the outlets of the UYRB were assessed. According to the projections, the eastern UYRB will tend to be warm-dry in the near-future relative to the reference period, whereas the western UYRB will tend to be warm-humid. Precipitation will decreases at a rate of 19.05-19.25 mm/10 a, and the multiyear average annual precipitation will vary between - 0.5 and 0.5 mm/day. Temperature is projected to increases significantly at a rate of 0.38-0.52 °C/10 a, and the projected multiyear average air temperature increase is approximately 1.3-1.5 ℃. The contribution of snowmelt runoff to the annual runoff in the UYBR is only approximately 4%, whereas that to the spring runoff is approximately 9.2%. Affected by climate warming, the annual average snowmelt runoff in the basin will be reduced by 36-39%, whereas the total annual runoff will be reduced by 4.1-5%, and the extreme runoff will be slightly reduced. Areas of projected decreased runoff depth are mainly concentrated in the southeast region of the basin. The decrease in precipitation is driving this decrease in the southeast, whereas the decreased runoff depth in the northwest is mainly driven by the increase in evaporation.