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Abstract This study aimed to retrospectively examine the computed tomography (CT) features of lung adenocarcinoma across different demographic groups. Preoperative chest CT findings from 1266 surgically resected lung adenocarcinoma cases were retrospectively analyzed. Lung adenocarcinomas were categorized based on CT characteristics into pure ground glass (pGGO), nodule-containing ground glass opacity (mGGO), and pure solid without containing ground glass opacity (pSD). These categories were correlated with sex, age, EGFR status, and five histopathological subtypes. The diameters of pGGO, mGGO, and pSD significantly increased across all patient groups (P 60 years) for both males (P = 0.002) and females (P = 0.027). The frequency of pSD was higher in the older age group for both sexes. A linear correlation between age and diameter was observed in the entire cohort as well as in the male and female groups (P

Mangroves are vital coastal ecosystems that provide crucial links between land and sea. Tree height is a key indicator for assessing mangroves’ health status. Currently, there are still numerous challenges in estimating mangrove tree height. In this study, multiple deep learning and shallow machine learning regression models were developed to accurately estimate mangrove tree height using multi-dimensional Light Detection and Ranging (LiDAR) point clouds and their derivatives. We constructed a novel CNN_RepMLP model for mangrove tree height mapping. We also further verified the applicability of different types of regression models in estimating mangrove tree heights, and explored the influence of different LiDAR-derived features on the inversion accuracy for tree heights. The results indicated the following: (1) The CNN_RepMLP displayed satisfactory performance in the inversion of mangrove tree heights, and exhibited better robustness and generalization ability than the convolutional neural network (CNN) model. (2) Among the different LiDAR-derived feature combinations, combining height variables with intensity variables can not only mitigate the negative impact of height variables on inversion models, but also enhance the mangrove tree height inversion accuracy. (3) The ensemble learning framework with ExtraTrees as the meta-model can make better use of the differences and complementarities between different single base models, and exhibited better accuracy in estimating the height of mangrove trees compared with other ensemble learning models. (4) Multiple machine learning models based on multi-dimensional UAV-LiDAR point-cloud-derived features are suitable for the inversion of mangrove tree height. The CNN_RepMLP model outperformed the CNN and stacking ensemble learning models and had more detailed differentiation in terms of mangrove tree height. Its prediction results can more realistically reflect the spatial differentiation characteristics of mangrove tree height.

ABSTRACTBackground: This study aims to investigate the correlation between NK and NKT cell proportion disparities and prognosis in patients with acute myeloid leukemia (AML).Methods: Forty-four cases of acute myeloid leukemia patients were selected, and flow cytometry was utilized to evaluate the expression of bone marrow NK and NKT cells. Next-generation sequencing technology was employed to detect genetic mutations in these 44 AML patients, and the rates of first induction remission and overall survival were recorded. Comparisons were made to analyze the respective differences in NK and NKT cell proportions among AML patients with various genetic mutations and risk stratifications.Results: The FLT-3-ITD+ group exhibited a significant increase in the proportion of NK cells compared to the normal control group and FLT3-ITD+/NPM1+ group, whereas the proportion of NKT cells was significantly decreased. Additionally, the CEBPA+ group showed an increased proportion of NKT cells compared to the TP53+ group and ASXL1+ group. The high-risk group had a higher proportion of NK cells than the intermediate-risk group, while the proportion of NKT cells was lower in the high-risk group compared to the intermediate-risk group.Patients achieving first induction remission displayed a higher proportion of NKT cells at initial diagnosis compared to those who did not achieve remission. The distribution of NK cells show significant differences among AML patients in different survival periods.Conclusion: This results implies that distinct genetic mutations may play a role not only in tumor initiation but also in shaping the tumor microenvironment, consequently impacting prognosis.

An improved leaf target detection method based on the YOLOv5s network is proposed to address the issues of low model detection accuracy and slow detection speed in potato leaf image target detection. Firstly, a deformable convolution replaces the standard convolution in YOLOv5s to ensure that the convolution region always covers the target region. Secondly, CBAM attention module is introduced into the convolutional module to enhance local feature extraction and fusion capability of the network, while WIoU_Loss serves as Bounding box loss function SRN-DeblurNet deblurnet is combined with YOLOv5s network to convert part of fuzzy images into clear ones before being integrated with multi-scale features for model prediction. To verify its effectiveness, we trained our model using Pytorch deep learning framework and achieved an accuracy rate of 90.3% and recall rate of 88%, which are respectively 8.6% and 8.9% higher than those obtained by YOLOv5s.

Autophagy during myocardial ischemia/reperfusion (MI/R) exacerbates cardiomyocyte injury. Melatonin (Mel) alleviates myocardial damage by regulating mitochondrial function and mitophagy, but the role of mitophagy in melatonin-induced cardioprotection remains unclear. This study aimed to explore the roles of sirtuin3 (SIRT3) and retinoid‐related orphan nuclear receptor‐α (RORα) in mitophagy during simulated ischemia reperfusion (SIR) in H9c2 cells. Our data showed that mitophagy was excessively activated after SIR injury, which was consistent with reduced cell survival, enhanced oxidative responses and mitochondrial dysfunction in H9c2 myocytes. Melatonin greatly enhanced cell viability, reduced oxidative stress and improved mitochondrial function. The effects of melatonin protection were involved in excessive mitophagy inhibition, as demonstrated by the reduced levels of mitophagy-linked proteins, including Parkin, Beclin1, NIX and BNIP3, and the LC3 II/LC3 I ratio and elevations in p62. Additionally, the decreases in SIRT3 and RORα in H9c2 myocytes after SIR were reversed by melatonin, and the above effects of melatonin were eliminated by small interfering RNA (siRNA)-mediated knockdown of SIRT3 and RORα. In brief, SIRT3 and RORα are two prospective targets in the cardioprotection of melatonin against mitophagy during SIR in H9c2 myocytes.

In this study, the extraction of sea ice drift from imagery captured by the 1-meter C-SAR 01 satellite (C-SAR/01) was facilitated utilizing the oriented fast and rotated brief algorithm within the feature tracking procedure, thus addressing the previously unexplored area of sea ice drift extraction using C-SAR/01 imagery. The retained keypoints and nearest neighbor distance ratio test for sea ice drift extracted from C-SAR/01 imagery were compared, indicating high reliability with 300 000 and 0.75, respectively. In addition, the local outlier factor algorithm is proposed in this article, which can effectively remove erroneous sea ice drift vectors. The sea ice drift extracted from C-SAR/01 was validated against manually extracted sea ice drift, revealing an uncertainty of 0.271 cm/s in speed and 8.331° in direction. Furthermore, the sea ice drift obtained from the algorithm in this study, when compared with sea ice drift from IABP buoys, exhibits high accuracy, reflecting the robustness of the algorithm.

Abstract The ability to leverage antibodies to agonize disease relevant biological pathways has tremendous potential for clinical investigation. Yet while antibodies have been successful as antagonists, immune mediators, and targeting agents, they are not readily effective at recapitulating the biology of natural ligands. Among the important determinants of antibody agonist activity is the geometry of target receptor engagement. Here, we describe an engineering approach inspired by a naturally occurring Fab-Fab homotypic interaction that constrains IgG in a unique i-shaped conformation. i-shaped antibody (iAb) engineering enables potent intrinsic agonism of five tumor necrosis factor receptor superfamily (TNFRSF) targets. When applied to bispecific antibodies against the heterodimeric IL-2 receptor pair, constrained bispecific IgG formats recapitulate IL-2 agonist activity. iAb engineering provides a tool to tune agonist antibody function and this work provides a framework for the development of intrinsic antibody agonists with the potential for generalization across broad receptor classes.

The safety and reliability of transmission line operations are critical to the delivery of electricity. Bird nests are one of the frequent potential factors affecting the safety of transmission lines. The main objective of this paper is to propose a small-sample learning method to detect bird nests on transmission lines. The method combines the two latest deep learning models, YOLOv5 and detection transformer (DETR). Inspired by biological vision, this method transfers the learning of bird nests in daily scenes to the recognition of bird nests on transmission lines. The proposed method is evaluated by two public datasets. The test on the first one presents a recognition rate of 95.50%, whereas the training set only contains ten homologous data and 80 non-homologous data. The second test shows that 85.54% of the samples are recognized by generalization without homologous training data. The results show that our method provides a way to identify bird nests on transmission lines with the help of bird nests of daily scenes under small sample conditions.

Abstract Background Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare interstitial lung disease. COVID-19 is associated with worse prognosis in previous lung diseases patients. But the prognosis of aPAP patients after infection with COVID-19 is unclear. In December 2022, China experienced a large-scale outbreak of Omicron variant of the SARS-CoV-2. In this study, we aim to explore the clinical outcomes of aPAP patients infected with COVID-19. Results A total of 39 aPAP patients were included in this study. 30.77% patients had a decrease in oxygen saturation after COVID-19 infection. We compared the two groups of patients with or without decreased oxygen saturation after COVID-19 infection and found that patients who had previous oxygen therapy (decreased oxygen saturation vs. non decreased oxygen saturation: 6/12 vs. 4/27, P = 0.043), with lower baseline arterial oxygen partial pressure (74.50 ± 13.61 mmHg vs. 86.49 ± 11.92 mmHg, P = 0.009), lower baseline DLCO/VA% [77.0 (74.3, 93.6) % vs. 89.5 (78.2, 97.4) %, P = 0.036], shorter baseline 6MWD [464 (406, 538) m vs. 532 (470, 575) m, P = 0.028], higher disease severity score (P = 0.017), were more likely to have decreased oxygen saturation after COVID-19 infection. Conclusion aPAP patients with poor baseline respiration have a higher probability of hypoxia after COVID-19 infection, but fatal events were rare.

The optimal allocation of agricultural water and land resources is of great significance in ensuring sustainable food production and economic benefits of farmers. However, agriculture, as an important carbon cycle ecosystem, has paid limited attention to carbon sequestration in the optimal allocation of water and land resources. Therefore, this study developed a new water-carbon-economy coupling model (WCECM) for optimal allocation of agricultural water and land resources. In this model, the minimum water scarcity, maximum carbon sequestration and maximum economic benefits are taken as the optimization objectives. In addition, surface water volume and groundwater volume and planting area etc. were defined as constraints, respectively. Then, the model was solved using the Non-dominated Sorting Genetic Algorithm III (NSGA-III) and the Entropy-weighted-TOPSIS evaluation method. The developed model was demonstrated in the largest Farm, Youyi Farm, which is one of commercial grain production base in China to analyze the optimization of water and land resources from 2010 to 2019. We found that the new WCECM, based on the simulation of a complex coupled water-carbon-economy system, can realize the optimal allocation of agricultural water and land resources to protect regional water resources, increase carbon sequestration and adjust the agricultural planting structure. In detail, through the multi-objective optimization model, the planting structure and the allocation ratio of surface water and groundwater irrigation water consumption are more suitable for this study area. After the optimization, the area planted with Rice was significantly reduced, the area planted with Maize was increased, and the area planted with Soybean did not change significantly compared with the first two crops. The planting structure has changed from focusing on paddy cultivation to dryland cultivation, with the ratio of Rice area, Maize area and Soybean area being 3:6:1. The water consumption is constrained within manageable limits, with an average annual irrigation water consumption of 2.01 × 108 m3. The amount of carbon sequestered has increased significantly, with an average annual increase of 7.8 × 108 kg. Meanwhile, the optimized economic benefits increased slightly, with a value of ¥2.35 billion. In short, optimization of water and land resources is beneficial for improving farmers' incomes, increasing carbon sequestration in agriculture, and conserving water resources.

As the climate warms, the thickening of the active layer of permafrost has led to permafrost melting and surface collapse, forming thermokarst landforms. These changes significantly impact regional vegetation, soil physicochemical properties, and hydrological processes, thereby exacerbating regional carbon cycling. This study analyzed the relationship between soil respiration rate (Rs), soil temperature (T), and volumetric water content (VWC) in the thermokarst depression zone of the headwater wetlands of Qinghai Lake, revealing their influence on these soil parameters. Results showed a significant positive correlation between soil temperature and Rs (p < 0.001), and a significant negative correlation between VWC and Rs (p < 0.001). The inhibitory effect of VWC on Rs in the thermokarst depression zone was stronger than under natural conditions (p < 0.05). Single-factor models indicated that the temperature-driven model had higher explanatory power for Rs variation in both the thermokarst depression zone (R2 = 0.509) and under natural conditions (R2 = 0.414), while the humidity-driven model had lower explanatory power. Dual-factor models further improved explanatory power, slightly more so in the thermokarst depression zone. This indicates that temperature and humidity jointly drive Rs. Additionally, during the daytime, temperature had a more significant impact on Rs under natural conditions, while increased VWC inhibited Rs. At night, the positive correlation between Rs and temperature in the thermokarst depression zone increased significantly. The temperature sensitivity (Q10) values of Rs were 3.32 and 1.80 for the thermokarst depression zone and natural conditions, respectively, indicating higher sensitivity to temperature changes at night in the thermokarst depression zone. This study highlights the complexity of soil respiration responses to temperature and humidity in the thermokarst depression zone of Qinghai Lake’s headwater wetlands, contributing to understanding carbon cycling in wetland ecosystems and predicting wetland carbon emissions under climate change.

Eight samples of No.11 coal in Sangshuping Mine were used for organic geochemical study, Gas chromatography-mass spectrometry (GC-MS) and X-ray fluorescence spectrometry (XRF) were combined with the test results of proximate analysis, sulfur forms and random vitrinite reflectance, the organic matter sources and coal-forming environment of No.11 coal from the Sangshuping mine, Shaanxi Province were comprehensively analyzed. The results indicate that the total sulfur content of the coal sample is 3.29%, and the mean vitrinite oil-leaching reflectance is 2.01%, which is high-sulfur lean coal. The phase parameters of major elements indicate that the coal samples are mainly formed in reductive sedimentary environment. There are two types of carbon number distribution of n-alkanes in saturated hydrocarbon: the front peak type main carbon peak is C16, and the back peak type is main carbon C26; Combined with the distribution characteristics of ∑C22−/∑C23+、(C21+C22)/(C28+C29)、Pr/nC17、Ph/nC18 indicated that the parent material of organic matter come from aquatic organisms and higher plants. The OEP value was between 0.49 to 1.05,with an average value of 0.84, indicating that No.11 coal of Sangshuping has undergone different degrees of biodegradation. In the analysis of saturated hydrocarbon steroidal terpanes, the ratio of w(Ts)/w(Tm) is between 0.83-1.21 and w(Ts)/[w(Ts)+w(Tm)] is between 0.45-0.55, indicating that the thermal evolution degree of coal sample is high. In the analysis of aromatic compounds, the methyl rearrangement of trimethylnaphthalene and the distribution characteristics of methyl phenanthrene index are correlated with the high thermal evolution degree of coal samples. The aromatic hydrocarbons were dominated by naphthalene, phenanthrene and biphenyl series, and the sulfur-containing compounds in the trifluorene series (oxygen-fluorene, sulfur-fluorene, fluorene) are obviously higher than the oxygen-containing compounds, which also indicates the coal-forming environment under higher salinity partial reduction conditions.

Karst wetlands are an important type of wetland among the global karst areas that suffer from serious ecosystem degradation. Chlorophyll content, an important parameter of vegetation functional traits, can indicate the photosynthetic activity, mutation and stress level, and nutritional state of vegetation. However, quantitative estimation of canopy chlorophyll content (CCC) of calcium-loving and alkali-resistant vegetation in karst wetlands using remote sensing technology for clarifying the relationship between canopy spectral reflectance and the CCC of vegetation communities remains a challenge. In this study, we propose a retrieval approach for estimating the CCC of seven typical vegetation communities in the largest karst wetland in China, using a combination of parameter/non– parameter estimation model, and unmanned aerial vehicle (UAV) multispectral images. We further evaluated the sensitivity of various spectral indices to the CCC of the vegetation communities and explored the influence of image feature distribution on CCC estimation accuracy. We revealed the variation patterns of leaf chlorophyll content (LCC) and CCC under different inundation frequencies in the karst wetland. We confirmed that the UAV-based inversion method proposed in this study achieved the CCC estimation of seven vegetation communities (R2 = 0.57 ∼ 0.93, RMSE = 8.80 SPAD ∼ 60.68 SPAD), and obtained high estimation accuracy (R2 = 0.77, RMSE = 22.04 SPAD) of Cladium chinense Nees (CCN, endemic vegetation in karst wetland). We found that the optimal reflectance ranges for estimating the CCC of the seven vegetation communities were 714 nm ∼ 746 nm and 814 nm ∼ 866 nm, and that the ChIrededge and MSR indices negatively influenced the CCC estimation of CCN and Carex baccans Nees (CBN), respectively. We demonstrated that vegetation communities with well-defined canopy structure (Triadica sebifera (Linnaeus) Small) achieved higher estimation accuracy with moderate uncertainty (ε = 10.80 % ∼ 15.49 %) than the herbaceous vegetation communities (CCN, CBN, and Cynodon dactylon (L.) Pers.). The bias of the CCC estimation based on linear regression and partial least squares regression models in different vegetation communities ranged from 1.61 % to 49.41 %. We confirmed that the magnitude of variations in LCC and CCC for these vegetation communities presented a decreasing pattern from that in high-frequency inundation communities to that in the low-frequency ones.

Abstract Aim To investigate the effectiveness of de-escalation of ticagrelor (from ticagrelor 90 mg to clopidogrel 75 mg or ticagrelor 60 mg) on the prognosis of patients with ST segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) after 3 months of oral dual antiplatelet therapy (DAPT). Methods From March 2017 to August 2021, 1056 patients with STEMI in a single centre, through retrospective investigation and analysis, were divided into intensive (ticagrelor 90 mg), standard (clopidogrel 75 mg after PCI) and de-escalation groups (clopidogrel 75 mg or ticagrelor 60 mg after 3 months of treatment with 90 mg ticagrelor) based on the type and dose of P2Y12 inhibitor 3 months after PCI, and the patients had a ≥ 12-month history of oral DAPT. The primary end point was major adverse cardiovascular and cerebrovascular events (MACCEs) during the 12-month follow-up period, including composite end points of cardiac death, myocardial infarction, ischaemia-driven revascularization and stroke. The major safety endpoint was bleeding events. Results The results showed that during the follow-up period, there was no statistically significant difference in the incidence of MACCEs between the intensive and de-escalation groups (P > 0.05). The incidence of MACCEs in the standard treatment group was higher than that in the intensive treatment group (P = 0.014), but the incidence of bleeding events in the de-escalation group was significantly lower than that in the standard group (9.3% vs. 18.4%, χ²=7.191, P = 0.027). The Cox regression analysis showed that increases in haemoglobin (HGB) (HR = 0.986) and estimated glomerular filtration rate (eGFR) (HR = 0.983) could reduce the incidence of MACCEs, while old myocardial infarction (OMI) (P = 0.023) and hypertension (P = 0.013) were independent predictors of MACCEs. Conclusion For STEMI patients undergoing PCI, the de-escalation scheme of ticagrelor to clopidogrel 75 mg or ticagrelor 60 mg at 3 months after PCI was related to the reduction of bleeding events, especially minor bleeding events, without an increase in ischaemic events.

BackgroundHealth cognitive promotion and protection is a critical topic. With the world’s aging population and rising life expectancy, there will be many people living with highly age-related dementia illnesses. Cardiovascular disease (CVD) and dementia share the same risk factors, such as unhealthy lifestyles and metabolic factors. These recognized risks associated with CVD and dementia frequently co-occur. CVD risk models may have a close association with dementia and cognitive decline. So, this systematic review aimed to determine whether CVD risk models were connected with dementia or cognitive decline and compare the predictive ability of various models.MethodsPubMed, Web of Science, PsychINFO, Embase, Cochrane Library, CNKI, Sinomed, and WanFang were searched from 1 January 2014 until 16 February 2023. Only CVD risk models were included. We used the Newcastle-Ottawa scale (NOS) for the quality assessment of included cohort studies and the Agency for Healthcare Research and Quality (AHRQ) for cross-sectional studies. The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement’s guidelines were followed in this systematic study.ResultsIn all, 9,718 references were screened, of which 22 articles were included. A total of 15 CVD risk models were summarized. Except for the Cardiovascular Health in Ambulatory Care Research Team (CANHEART) health index, the other 14 CVD risk models were associated with dementia and cognitive decline. In comparison, different CVD risk models and domain-specific cognitive function correlation variation depended on cohort characteristics, risk models, cognitive function tests, and study designs. Moreover, it needed to be clarified when comparing the predicting performance of different CVD risk models.ConclusionIt is significant for public health to improve disease risk prediction and prevention and mitigate the potential adverse effects of the heart on the brain. More cohort studies are warranted to prove the correlation between CVD risk models and cognitive function. Moreover, further studies are encouraged to compare the efficacy of CVD risk models in predicting cognitive disorders.

Phytoplankton community spatial scales vary in typical coastal bay-river systems under natural and anthropogenic effects. However, their relative importance in shaping phytoplankton spatial heterogeneity has been largely uncharacterized in the literature. In this study, we performed comprehensive analyses using field monitoring, meteorological, and remote sensing datasets from a coastal bay-river system in South China (the Guangdong-Hong Kong-Macao Greater Bay-Pearl River tributaries) to examine phytoplankton spatial heterogeneity and main effects. We showed that water quality in the four water bodies of the typical coastal bay-river system in South China were relatively poor. Phytoplankton community abundance, taxonomic grouping, dominant species, and species similarity varied significantly in response to environmental gradients. We showed that Cyanophyta, Bacillatiophyta, and Chlorophyta were dominant phyla, and we observed regional variations in taxonomic groups and dominant species. Phytoplankton abundance was significantly higher in Dongjiang River and water bodies in branched bays when compared with other regions due to nutrient input from extensive agricultural and urban development, where the dominant phylum was Cyanophyta. Cyclotella (Bacillariophyta) had relatively high abundance and was widely distributed throughout the coastal bay-river system, except in the Dongjiang River. Melosira (Bacillariophyta) had relatively high abundance in Dongjiang and Xijiang Rivers, Merismopedia (Cyanophyta) dominated in the Dongjiang River and highly urbanized branched bay areas, while Microcystis (Cyanophyta) only dominated in Beijiang and Xijiang Rivers. Dominant species distributions showed apparent spatial heterogeneity in phytoplankton community composition. Species similarities between different water bodies were generally low, but phytoplankton species similarities between the Dongjiang River and water bodies in the branched bay area were relatively high, which indicated that water exchange associated with freshwater and nutrient inputs may have profoundly influenced species dispersal and dominant phytoplankton species. Redundancy analyses (RDA) demonstrated that pH, elevation, photosynthetically active radiation (PAR), dissolved active phosphorus (SRP), total dissolved phosphorus (TP), total nitrogen (TN), and nitrate nitrogen (NO3−-N) values - associated with nutrient and climate indicators were the main factors explaining structured phytoplankton spatial distributions. Variance partitioning analyses (VPA) showed that phytoplankton community variations were explained by anthropogenic factors (eutrophication) in summer. Our study improves our understanding of the natural and anthropogenic effects on phytoplankton spatial heterogeneity and provides basic study data for long-term phytoplankton evolution from river to bay areas.

Sodium in the coals of West China has received persistent attention due to its high contents and severe pollutions’ problems during coal utilization. A total of seven drill samples of the Jurassic coals from Tatuo coalfield, Qinghai Province, were collected and analysed using optical microscopy, scanning electron microscopy in conjunction with energy-dispersive X-ray spectrometry, X-ray powder diffraction, inductively coupled plasma mass spectrometry and X-ray fluorescence spectrometry. The results indicate that the Tatuo coal is of lower-high ash, medium volatile matter and ultra-low sulphur bituminous coal. Tatuo coal contains much more Na 2 O (> 2%), and belongs to high-sodium coal. The maceral index and element ratios of Sr/Cu, Fe/Mn and Sr/Ba showed that Tatuo coal was formed in a terrestrial peat swamp environment. The minerals in Tatuo coal, including clay minerals and halite, quartz, gypsum and rutile, are mainly concentrated in the bottom and top parts of the coal seam. Combined with scanning electron microscopy in conjunction with energy-dispersive X-ray spectrometry and optical microscope characteristics, the sodium could be carried into the peat/coal after the peat formation by basin fluids. The East Kunlun orogenic belt may be the main source of these minerals.

Background Vascular calcification (VC) has been observed in patients with hemodialysis, whereas few studies have investigated calcification in the upper extremity vasculature. Both ultrasound and X-ray are used to investigate the calcification of arteries in patients. However, there is a lack of data on the consistency between these two methods. The aim of this study was to investigate the occurrence of VC in the radial and ulnar arteries of hemodialysis patients and investigate the detection consistency in VC between ultrasound and X-ray. Methods Ultrasound and X-ray examinations were performed in the radial and ulnar arteries of both the left and right upper extremities of 40 patients on hemodialysis. The calcification status of arteries was evaluated by the calcification index from ultrasound and X-ray respectively. Clinical variables of patients were collected from all the involved patients. Results Of the 40 patients, VC was detected in 31 patients by ultrasound, while X-ray detected VC in 22 patients. Compared to ultrasound assessment, X-ray assessment was 73.21% sensitive but only 66.35% specific with a positive predictive value of 53.95% for detecting calcifications in the radial or ulnar artery. The level of agreement between ultrasound and X-ray results was fair. In addition, our data showed that more ulnar arteries had VCs than the corresponding radial arteries. Conclusion Ultrasound is more sensitive in detecting the presence of calcified atherosclerotic lesions. Ultrasound and X-ray exhibited fair consistency. Ultrasound screening for upper extremity radial and ulnar arteries in hemodialysis patients may deserve attention to explore its clinical significance.

Systemic sclerosis (SSc) is a connective tissue disease with an unknown etiology. Clinically, it is characterized by localized or diffuse skin thickening and fibrosis. The pathogenesis of SSc includes microvascular injury, autoimmune-mediated inflammation, and fibroblast activation. These processes interact and contribute to the diverse clinicopathology and presentation of SSc. Given the limited effectiveness and substantial side effects of traditional treatments, the treatment strategy for SSc has several disadvantages. Mesenchymal stem cells (MSCs) are expected to serve as effective treatment options owing to their significant immunomodulatory, antifibrotic, and pro-angiogenic effects. Exosomes, secreted by MSCs via paracrine signaling, mirror the effect of MSCs as well as offer the benefit of targeted delivery, minimal immunogenicity, robust reparability, good safety and stability, and easy storage and transport. This enables them to circumvent the limitations of the MSCs. When using exosomes, it is crucial to consider preparation methods, quality standards, and suitable drug delivery systems, among other technical issues. Therefore, this review aims to summarize the latest research progress on MSCs and exosomes in SSc, offering novel ideas for treating SSc.

Pretherapeutic serological parameters play a predictive role in pathologic risk factors (PRF), which correlate with treatment and prognosis in cervical cancer (CC). However, the method of pre-operative prediction to PRF is limited and the clinical availability of machine learning methods remains unknown in CC. Overall, 1260 early-stage CC patients treated with radical hysterectomy (RH) were randomly split into training and test cohorts. Six machine learning classifiers, including Gradient Boosting Machine, Support Vector Machine with Gaussian kernel, Random Forest, Conditional Random Forest, Naive Bayes, and Elastic Net, were used to derive diagnostic information from nine clinical factors and 75 parameters readily available from pretreatment peripheral blood tests. The best results were obtained by RF in deep stromal infiltration prediction with an accuracy of 70.8% and AUC of 0.767. The highest accuracy and AUC for predicting lymphatic metastasis with Cforest were 64.3% and 0.620, respectively. The highest accuracy of prediction for lymphavascular space invasion with EN was 59.7% and the AUC was 0.628. Blood markers, including D-dimer and uric acid, were associated with PRF. Machine learning methods can provide critical diagnostic prediction on PRF in CC before surgical intervention. The use of predictive algorithms may facilitate individualized treatment options through diagnostic stratification.

BackgroundThis study aimed to systematically evaluate the effects of different types and doses of pretreatment with P2Y12 inhibitors in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary intervention (PCI).MethodsElectronic databases were searched for studies comparing pretreatment with different types and doses of P2Y12 inhibitors or comparison between P2Y12 inhibitor pretreatment and nonpretreatment. Electronic databases included the Cochrane Library, PubMed, EMBASE, and Web of Science. Literature was obtained from the establishment of each database until June 2022. The patients included in the study had pretreatment with P2Y12 inhibitors with long-term oral or loading doses, or conventional aspirin treatment (non-pretreatment). The primary endpoint was major adverse cardiac and cerebrovascular events (MACCEs) during follow-up within 30 days after PCI, which included determining the composite endpoints of cardiac death, myocardial infarction, ischemia-driven revascularization, and stroke. The safety endpoint was a major bleeding event.ResultsA total of 119,014 patients from 21 studies were enrolled, including 13 RCTs and eight observational studies. A total of six types of interventions were included—nonpretreatment (placebo), clopidogrel pretreatment, ticagrelor pretreatment, prasugrel pretreatment, double loading pretreatment (double loading dose of clopidogrel, ticagrelor, prasugrel) and P2Y12 inhibitors pretreatment (the included studies did not distinguish the types of P2Y12 inhibitors, including clopidogrel, ticagrelor, and prasugrel). The network meta-analysis results showed that compared to patients without pretreatment, patients receiving clopidogrel pretreatment (RR = 0.78, 95% CI:0.66, 0.91, P 0.05).ConclusionsIn patients with NSTE-ACS, pretreatment with P2Y12 inhibitors before percutaneous intervention reduced the incidence of recurrent ischemic events without increasing the risk of major bleeding after PCI compared with nonpretreatment. Clopidogrel or double loading dose P2Y12 inhibitors can be considered for the selection of pretreatment drugs.

Introduction: Pulmonary fibrosis (PF) is a severe disease that can lead to respiratory failure and even death. However, currently there is no effective treatment available for patients with PF. Mesenchymal stem cells (MSCs) have been recently shown to have therapeutic potential for PF. We analyzed the literature focused of MSCs and PF to provide a comprehensive understanding of the relationship between MSCs and PF.Methods: We searched the Web of Science Core Collection database for literature from 2002 through 2021 that involved MSCs and PF. The included studies were then analyzed using CiteSpace and VOSviewers software.Results: A total of 1,457 studies were included for analysis. Our findings demonstrated the following: 1) an increasing trend of MSC and PF research; 2) among the 54 countries/regions of author affiliations, the United States was the most frequent, and the University of Michigan (n = 64, 2.8%) was the top institution; 3) Rojas Mauricio published the most articles and PLOS ONE had the most related studies; and 4) keywords, such as idiopathic pulmonary fibrosis, mesenchymal stem cells, and systemic sclerosis, were listed more than 100 times, indicating the research trend. Other common keywords, such as inflammation, myofibroblasts, fibroblasts, aging, telomerase or telomere, and extracellular matrix demonstrate research interests in the corresponding mechanisms.1) The number of publications focused on MSCs and PF research increased during the study period; 2) Among the 54 countries/regions of author affiliations, most articles were published in the United States of America, and the University of Michigan (n = 64, 2.8%) had the largest number of publications; 3) Rojas Mauricio published the most articles and PLOS ONE had the most related studies; 4) Keywords, such as idiopathic pulmonary fibrosis, MSCs, and systemic sclerosis, were listed more than 100 times, representing a research trend. Other common keywords included inflammation, myofibroblasts, fibroblasts, aging, telomerase or telomere, and extracellular matrix.Discussion: During the past 2 decades, MSCs have been proposed to play an important role in PF treatment. An increasing amount of literature focused on MSCs and PF research has been published. Our findings provide insight into the current status and research trends in the field of MSCs and PF research during the past 2 decades, which could help researchers understand necessary research directions. In the future, more preclinical and clinical studies should be conducted in this field to support the application of MSCs in the treatment of PF.

Introduction: Acute respiratory distress syndrome (ARDS) remains a major clinical challenge for patients in intensive care units. Determining the differential mechanisms underlying ARDS with different etiologies is a key goal to improve the effectiveness of ARDS therapy. Despite growing evidence that different immune cell types are involved in ARDS, the role of altered immune cell subpopulations in disease progression is unelucidated.Methods: In this study, we combined scRNA-seq and bulk-level sequencing to analyze the transcriptomes of peripheral blood mononuclear cells from healthy volunteers and patients with septic ARDS (sep-ARDS) and pneumonic ARDS (PNE-ARDS).Results: Our data revealed differential alterations at the cellular and molecular levels and within biological signaling pathways in ARDS with different etiologies. The dynamics of neutrophils, macrophages (Macs), classical dendritic cells (cDCs), myeloid-derived suppressive cells (MDSCs), and CD8+ T cells varied significantly among groups of different samples, with neutrophils and cDCs at higher, and Macs at significantly lower, amounts in the patients with sep-ARDS. Furthermore, MDSCs were highly enriched only in the sep-ARDS patients, whereas a higher abundance of CD8+ T cells was observed in patients with PNE-ARDS. In addition, these cell subpopulations were found to be significantly involved in apoptosis, inflammatory, and immune-related pathways. In particular, a significant enhancement of the oxidative stress response was observed in the neutrophil subpopulation.Conclusion: Our study shows that the composition of cells involved in the main peripheral circulation differs in patients with ARDS with different etiologies. Studying the role and mechanism of action of these cells during ARDS will provide new opportunities for the treatment of this condition.

Acute coronary syndrome (ACS), diagnosed by optical coherence tomography (OCT), is caused primarily by plaque rupture, plaque erosion, and calcified nodules. Plaque erosion is more common in patients with non-ST-segment elevation myocardial infarction than ST-segment elevation myocardial infarction. This study reports the details of a case of ACS caused by massive thrombus formation due to plaque erosion. The factors associated with plaque erosion and thrombosis could not be confirmed on the basis of clinical examination findings and the physicians’ experience; therefore, the initial diagnosis of an ischemic event was replaced by a diagnosis of rapid plaque progression, as microscopically confirmed by OCT. Therefore, OCT examination must be performed for blurred or “rapidly progressing” lesions identified through angiography.

Abstract Background Spontaneous pneumothorax has a high incidence and high rate of recurrence in patients with lymphangioleiomyomatosis (LAM). The risk factors for pneumothorax and the effects of sirolimus on pneumothorax in patients with LAM are unknown. In our study, multivariate logistic regression was applied to a cross-sectional cohort to investigate factors associated with pneumothorax in LAM patients. Kaplan–Meier analysis was applied in the historical prospective self-controlled study to determine whether sirolimus reduces the risk of pneumothorax recurrence in patients with LAM. Results Of the 399 patients registered with LAM-CHINA at our center between May 10, 2017 and August 31, 2020, 142 had a history of pneumothorax at registration. High CT grade and age at presentation ≤ 35 years were associated with a higher risk of pneumothorax in patients with LAM. Postmenopausal status was correlated with a lower risk of pneumothorax. In the historical prospective self-controlled study, the 5-year probability of pneumothorax recurrence was 80% lower in the sirolimus group than in the control group (hazard ratio for pneumothorax recurrence, 0.20; 95% CI, 0.14 to 0.30, P

Background: Pediatric cardiac surgery is associated with a high risk of mortality and morbidity. The aim of this study was to determine if intraoperative dexmedetomidine therapy could improve survival after pediatric cardiac surgery. Methods: We conducted a retrospective review of 1384 consecutive children who underwent pediatric cardiac surgery. Amongst these, 889 received dexmedetomidine therapy and 495 did not. All children were followed for 1 year. Their in-hospital and long-term outcomes were compared by multivariate logistic regression to minimize bias, and propensity-score matched adjustment was used. Results: Children who received dexmedetomidine had lower mortality during the 30-day postoperative period compared to children who did not (1.57% vs. 4.24%; adjusted hazard ratio [HR]: 0.448; 95% confidence interval [CI]: 0.219–0.916, p = 0.028), as well as after 1 year (2.36% vs. 6.67%; adjusted [HR]: 0.487; 95% [CI]: 0.274–0.867, p = 0.014). The two groups showed no significant differences in cardiovascular complications. Conclusions: Dexmedetomidine administered intraoperatively reduced 30-day and 1-year mortality in children undergoing pediatric cardiac surgery.

In this work, Mackinawite (FeSm) was synthesized by homogeneous precipitation method, and flower-like nanoparticles formed by the aggregation of nanosheets with a preferred orientation along the (001) plane. The heterogeneous Fenton-like degradation performance of FeSm on rhodamine B (RhB) was investigated, results illustrated that RhB degradation was the synergistic effect of adsorption, Fenton, and a heterogeneous Fenton-like reaction. In repeated experiments, the reduction of reactivity was attributed to the oxidation of FeSm into lepidocrocite, whereas lepidocrocite has relatively low hydroxyl radicals (•OH) production reactivity. Thus, it showed excellent degradation effects in long-time degradation of RhB. Photoluminescence technology and free radical capture experiments demonstrated that •OH produced on the surface of catalyst was the main active species to remove RhB. In addition, the Fe species on the surface of FeSm was the main active center for surface-mediated reactions. A total organic carbon test revealed that the degradation was not complete and degradation intermediates were formed. Liquid chromatography-mass spectrometry technology was used to identify the degradation intermediates. On this basis, possible degradation pathways were proposed. HIGHLIGHTS Flower-like Mackinawite (FeSm) nanoparticles were synthesized using an homogeneous precipitation method.; FeSm was used as an heterogeneous Fenton-like catalyst to degrade RhB.; The reduction of FeSm reuse activity was mainly attributed to the formation of lepidocrocite with lower activity.; •OH surface-bounded of FeSm was the main active species for RhB degradation.; The possible degradation pathway of RhB was speculated.;

Antibodies are fundamental effectors of humoral immunity, and have become a highly successful class of therapeutics. There is increasing evidence that antibodies utilize transient homotypic interactions to enhance function, and elucidation of such interactions can provide insights into their biology and new opportunities for their optimization as drugs. Yet the transitory nature of weak interactions makes them difficult to investigate. Capitalizing on their rich structural data and high conservation, we have characterized all the ways that antibody fragment antigen-binding (Fab) regions interact crystallographically. This approach led to the discovery of previously unrealized interfaces between antibodies. While diverse interactions exist, β-sheet dimers and variable-constant elbow dimers are recurrent motifs. Disulfide engineering enabled interactions to be trapped and investigated structurally and functionally, providing experimental validation of the interfaces and illustrating their potential for optimization. This work provides first insight into previously undiscovered oligomeric interactions between antibodies, and enables new opportunities for their biotherapeutic optimization.

Abstract Background We investigated the feasibility of two biomarkers of endothelial damage (Syndecan-1 and thrombomodulin) in coronavirus disease 2019 (COVID-19), and their association with inflammation, coagulopathy, and mortality. Methods The records of 49 COVID-19 patients who were admitted to an intensive care unit (ICU) in Wuhan, China between February and April 2020 were examined. Demographic, clinical, and laboratory data, and outcomes were compared between survivors and non-survivors COVID-19 patients, and between patients with high and low serum Syndecan-1 levels. The dynamics of serum Syndecan-1 levels were also analyzed. Results The levels of Syndecan-1 were significantly higher in non-survivor group compared with survivor group (median 1031.4 versus 504.0 ng/mL, P = 0.002), and the levels of thrombomodulin were not significantly different between these two groups (median 4534.0 versus 3780.0 ng/mL, P = 0.070). Kaplan–Meier survival analysis showed that the group with high Syndecan-1 levels had worse overall survival (log-rank test: P = 0.023). Patients with high Syndecan-1 levels also had significantly higher levels of thrombomodulin, interleukin-6, and tumor necrosis factor-α. Data on the dynamics of Syndecan-1 levels indicated much greater variations in non-survivors than survivors. Conclusions COVID-19 patients with high levels of Syndecan-1 develop more serious endothelial damage and inflammatory reactions, and have increased mortality. Syndecan-1 has potential for use as a marker for progression or severity of COVID-19. Protecting the glycocalyx from destruction is a potential treatment for COVID-19.

Abstract Background The differential diagnosis of diffuse cystic lung disease (DCLD) is a clinical challenge. We wish to analyze the distribution of the etiology of DCLD based on data from a single lymphangioleiomyomatosis (LAM) clinic. Methods All DCLD patients at the LAM Clinic of Peking Union Medical College Hospital between January 2006 and December 2019 were analyzed. Information on the demographic, clinical, radiological, and pathological features was collected. Results A total of 1010 patients with DCLD on CT scan were evaluated. A sum of 711(70.4%) patients were diagnosed with definite or probable LAM. Other diagnoses included Birt–Hogg–Dubé syndrome (46), Sjogren's syndrome (38), pulmonary Langerhans cell histiocytosis (14), lung tumors (3), Castleman disease (2), antineutrophil cytoplasmic antibody-associated vasculitis (2), systemic lupus erythematosus (1), Marfan syndrome (1), amyloidosis (1), congenital cystic adenomatoid malformation of the lung (1), and pleuroparenchymal fibroelastosis (1). In the 38 patients diagnosed with Sjogren's syndrome, 2 were diagnosed with light-chain deposition disease, 2 were diagnosed with amyloidosis and 1 was diagnosed with lymphocytic interstitial pneumonia. One hundred and eighty-nine patients (18.7%) were undiagnosed. Lung biopsy results were available in 27 patients in the undiagnosed DCLD group but did not provide a diagnosis. Conclusion Approximately 70% of DCLD patients in our LAM clinic had LAM. The common differential diagnoses included Birt–Hogg–Dubé syndrome, Sjogren’s syndrome, and pulmonary Langerhans cell histiocytosis. Detailed clinical information and laboratory, genetic, and pathological investigations provide correct diagnoses in most patients with DCLD.

Abstract Background Transbronchial lung biopsy (TBLB) in the diagnosis of lymphangioleiomyomatosis (LAM) is not a common approach, although TBLB is often performed in diffuse lung diseases. We aimed to examine the diagnostic value and safety of TBLB in LAM patients based on the data collected in our center. Methods We reviewed LAM patients registered in our LAM Clinic from December 8, 2006, to December 31, 2019. All patients with definite or probable diagnosis of LAM who had been examined using TBLB were included. All available pathology slides were reviewed by an experienced LAM pathologist. All complications were reviewed by the medical records and confirmed using telephone interviews. Results The pathology results of 86 patients (including 74 definite LAM and 12 probable LAM) were available. The positive rate of TBLB in LAM patients was 49/86 (57.0%). The positive rates of SMA, HMB-45, ER, and PR in LAM patients were 97.6%, 93%, 84.6%, and 78.4% respectively. The positive rate of TBLB was 40%, 60% and 60.8% in patients with CT Grade I, Grade II, and Grade III respectively, and the difference was not significant. Patients who had 3–4 or 5–6 biopsied specimens had a higher rate of diagnosis than those with 1–2 biopsied specimens. Four patients (5.6%) reported pneumothorax. No major hemoptysis was reported. Conclusions TBLB is a feasible and safe procedure for obtaining a pathological diagnosis of LAM. Taking more than 2 samples during the biopsy procedure increased the rate of diagnosis.

Abstract Introduction Acute liver inflammatory reactions contribute to many health problems; thus, it is critical to understand the underlying pathogenic mechanisms of acute hepatitis. In this study, an experimental in vivo model of concanavalin A (ConA)‐induced hepatitis was used. Materials and Methods C57BL/6 (wild‐type, WT) or inducible nitric oxide synthase‐deficient (iNOS−/−) mice were injected with PBS or 15 mg/kg ConA via tail vein. Detection of liver injury by histological examination and apoptosis, and flow cytometry to detect the effect of immune cells on liver injury. Results iNOS−/− mice had lower levels of the liver enzymes aspartate aminotransferase and alanine aminotransferase, suggesting that they were protected against ConA‐induced pathological liver injury and that iNOS participated in the regulation of hepatitis. Furthermore, iNOS deficiency was found to lower CD86 expression and suppressed the messenger RNA levels of inflammatory factors in the liver. In vitro experiments also demonstrated that iNOS deficiency suppressed the sequential phosphorylation of the mitogen‐activated protein kinase pathway cascade, thereby inhibiting the M1 polarization of macrophages and consequently suppressing the transcription of inflammation factors. Conclusion iNOS may contribute to ConA‐induced inflammation by promoting the activation of proinflammatory macrophages.

The human brain dynamically shifts between a predominantly integrated state and a predominantly segregated state, each with different roles in supporting cognition and behavior. However, no studies to date have investigated lesions placed in different regions of the cerebral cortex to determine the effects on the temporal balance of integration and segregation. Here, we used the integrated state occurrence rate to measure the temporal balance of integration and segregation in the resting brain. Based on dynamic mean-field models coupled through the individual's structural white matter connections, neural activity was modeled. By lesioning different individual nodes from the model, our results implied that the impact of lesions reaches far beyond focal damage and could impair cognition by affecting system-level dynamics. Lesions in a portion of the nodes in the visual, somatomotor, limbic, and default networks significantly compromised the temporal balance of integration and segregation. Crucially, the effects of lesions in different regions could be predicted based on the hierarchical axis inferred from the T1w/T2w map and specific graph measures of structural brain networks. Taken together, our findings indicate the possibility of significant contributions of anatomical heterogeneity to the dynamics of functional network topology. Although still in its infancy, computational modeling may provide an entry point for understanding brain disorders at a causal mechanistic level, possibly leading to novel, more effective therapeutic interventions.

Microplastics are widely distributed, such as oceans, rivers and the atmosphere, with many opportunities for human exposure and potential health risks. Polystyrene microplastic (PS-MPS) exposure has been found to cause sperm damage to mice; however, the mechanism by which this happens remains unclear. Here, GC-2 cells, a mouse spermatocyte line, were exposed to 5 µm PS-MPS to investigate mitochondrial damage. The results showed that 5 µm PS-MPS decreased ATP content, reduced the mitochondrial membrane potential, damaged the integrity of the mitochondrial genome, and caused an imbalance of homoeostasis between mitochondrial division and fusion. The mitochondrial PINK1/Parkin autophagy pathway was activated. Time-series analysis revealed that PS-MPS damaged the mitochondrial structure through cellular oxidative stress, and mitochondrial function was maintained to some extent after PS-MPS damage. This study revealed the mitochondrial toxicity of polystyrene microplastics, thus providing a basis for understanding the causes of sperm damage by polystyrene microplastics.

Abstract Background Lymphangioleiomyomatosis (LAM) is a rare disease that almost exclusively affects women of reproductive age. Patients are warned of the increased risks if they become pregnant. However, information on pregnancy in patients after the diagnosis of LAM is limited. Methods Patients were collected from the LAM registry study at Peking Union Medical College Hospital, Beijing, China. Patients with a history of pregnancy after the diagnosis of LAM were included. Medical records were reviewed, and baseline information and data during and after pregnancy were collected in May 2018. Results Thirty patients with a total of 34 pregnancies after the diagnosis of LAM were included. Livebirth, spontaneous abortion and induced abortion occurred in 10, 6 and 18 pregnancies, respectively. Sirolimus treatment was common (17/34). A total of 6/10, 5/6, and 6/18 patients with livebirths, spontaneous abortions, and induced abortions respectively, had a history of sirolimus treatment. Ten pregnancies (29.4%) had LAM-associated complications during pregnancy, including the exacerbation of dyspnea in 7 patients, pneumothorax in 3 patients (2 resulting in induced abortion and 1 successful parturition), and spontaneous bleeding of renal angiomyolipomas in 2 patients (both having successful parturition). No chylothorax was found during pregnancy. There were six pregnancies in six patients (17.6%) who had a history of livebirth after sirolimus treatment for LAM (all having successful parturition and healthy infants); two of these patients reported exacerbated dyspnea after parturition compared with before pregnancy. Conclusions Patients with LAM, especially those taking sirolimus before pregnancy, were at a higher risk of spontaneous abortion. Complications such as pneumothorax, bleeding of renal angiomyolipoma, and exacerbated dyspnea during pregnancy were common. In patients without spontaneous abortion, sirolimus discontinuation before or during pregnancy did not lead to increased adverse neonatal outcomes.

Resting-state functional connectivity hypernetworks, in which multiple nodes can be connected, are an effective technique for diagnosing brain disease and performing classification research. Conventional functional hypernetworks can characterize the complex interactions within the human brain in a static form. However, an increasing body of evidence demonstrates that even in a resting state, neural activity in the brain still exhibits transient and subtle dynamics. These dynamic changes are essential for understanding the basic characteristics underlying brain organization and may correlate significantly with the pathological mechanisms of brain diseases. Therefore, considering the dynamic changes of functional connections in the resting state, we proposed methodology to construct resting state high-order functional hyper-networks (rs-HOFHNs) for patients with depression and normal subjects. Meanwhile, we also introduce a novel property (the shortest path) to extract local features with traditional local properties (cluster coefficients). A subgraph feature-based method was introduced to characterize information relating to global topology. Two features, local features and subgraph features that showed significant differences after feature selection were subjected to multi-kernel learning for feature fusion and classification. Compared with conventional hyper network models, the high-order hyper network obtained the best classification performance, 92.18%, which indicated that better classification performance can be achieved if we needed to consider multivariate interactions and the time-varying characteristics of neural interaction simultaneously when constructing a network.

Abstract Background COVID-19 is a viral respiratory disease caused by the severe acute respiratory syndrome-Coronavirus type 2 (SARS-CoV-2). Patients with this disease may be more prone to venous or arterial thrombosis because of the activation of many factors involved in it, including inflammation, platelet activation and endothelial dysfunction. Interferon gamma inducible protein-10 (IP-10), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein 1-alpha (MIP1α) are cytokines related to thrombosis. Therefore, this study focused on these three indicators in COVID-19, with the hope to find biomarkers that are associated with patients’ outcome. Methods This is a retrospective single-center study involving 74 severe and critically ill COVID-19 patients recruited from the ICU department of the Tongji Hospital in Wuhan, China. The patients were divided into two groups: severe patients and critically ill patients. The serum IP-10, MCP-1 and MIP1α level in both groups was detected using the enzyme-linked immunosorbent assay (ELISA) kit. The clinical symptoms, laboratory test results, and the outcome of COVID-19 patients were retrospectively analyzed. Results The serum IP-10 and MCP-1 level in critically ill patients was significantly higher than that in severe patients (P

Abstract Background Treatment of autoimmune pulmonary alveolar proteinosis (aPAP) by inhaled granulocyte-macrophage colony stimulating factor (GM-CSF) is considered safe and effective. Evidence of benefit from GM-CSG inhalation for mild to moderate aPAP patients is limited. Methods In this multicenter, randomized, open-labeled clinical trial, 36 aPAP patients with mild to moderate disease severity were randomized into either the GM-CSF treatment group or control group. Inhaled GM-CSF was prescribed for 6 months, and patients received follow-up for another 18 months without treatment. Physiological features of the patients were analyzed. Results There were 36 patients (19 in the treatment group, 17 in the control group) included. There were no significant differences in the primary endpoints as measured by the change of alveolar arterial oxygen gradient (A-aDO2) from the baseline values to the values obtained during treatment or during the following 18-month non-treatment observation period [control group vs. treatment group: 0.51 ± 12.09 mmHg vs. -0.35 ± 13.76 mmHg, p = 0.848 (3 month); 1.85 ± 11.21 mmHg vs. 7.31 ± 8.81 mmHg, p = 0.146 (6 months); 6.05 ± 11.14 mmHg vs. 6.61 ± 10.64 mmHg, p = 0.899 (24 months)]). Percentage of diffusion capacity predicted (DLCO%) and percentage of total lung capacity predicted (TLC%), however, were significantly improved in the treatment group by the end of the study (P = 0.010 and 0.027). St. George Respiratory questionnaire (SGRQ) scores were better after 6 months treatment with GM-CSF compared to the control group, and the benefits of treatment were maintained throughout the observation period. No severe side effects were observed during the study. Conclusion Six months of inhaled GM-CSF treatment had no effect on the alveolar–arterial oxygen gradient in patients with mild to moderate pulmonary alveolar proteinosis. There were changes in some clinical or laboratory measures, but no clinically important changes were noted at the end of study. (Clinical Trial Registry: NCT02243228, Registered on September 17, 2014, https://www.clinicaltrials.gov/ct2/show/NCT02243228?term=NCT02243228&draw=2&rank=1 )

Abstract Objective To evaluate the effects of yoga on exercise capacity and quality of life in patients with lymphangioleiomyomatosis (LAM), a rare cystic lung disease in women. Patients and methods This was a nonrandomized, controlled study conducted in Beijing, China (August 27, 2017 – April 26, 2018). Twenty-six participants were allocated to the intervention (yoga) group (n = 13) or control group (n = 13). The yoga intervention involved a 24-week program of yoga class training for 90 min once a week and no fewer than 2 at-home sessions per week (at least 15 min per session). The 6-min walking distance (6MWD), lung function, serum vascular endothelial growth factor-D (VEGF-D) levels, quality of life, and symptoms of anxiety and depression were measured at baseline, 12-week and 24-week follow-up. An incremental cardiopulmonary exercise test was conducted at baseline and the 24-week follow-up. Results Eleven patients completed the yoga training program. The yoga group exhibited improvements in the following outcomes versus those of the control group: 6MWD (+ 55 ± 29 m vs + 18 ± 49 m, P = 0.04), anaerobic threshold (3.4 ± 2.4 ml/min/kg vs 1.6 ± 1.4 ml/min/kg, P = 0.035) and peak work load (11.7 ± 14.6 W vs 0.2 ± 9.1 W, P = 0.027). There was no significant difference in peak oxygen consumption (VO2peak), lung function, VEGF-D level, and quality of life between the yoga and control groups. No adverse effects were found in the yoga group. Conclusion Yoga is a feasible and safe intervention for pulmonary rehabilitation and potentially improves exercise capacity in patients with LAM. Trial registration (Clinical trial registration number at www.chictr.org.cn : ChiCTR-OON-1701274)

Abstract Background Exposure to air pollution is associated with chronic obstructive pulmonary disease (COPD). However, findings on the effects of air pollution on lung function and systemic inflammation in Chinese COPD patients are inconsistent and scarce. This study aims to evaluate the effects of ambient air pollution on lung function parameters and serum cytokine levels in a COPD cohort in Beijing, China. Methods We enrolled COPD participants on a rolling basis from December 2015 to September 2017 in Beijing, China. Follow-ups were performed every 3 months for each participant. Serum levels of 20 cytokines were detected every 6 months. Hourly ambient pollutant levels over the same periods were obtained from 35 monitoring stations across Beijing. Geocoded residential addresses of the participants were used to estimate daily mean pollution exposures. A linear mixed-effect model was applied to explore the effects of air pollutants on health in the first-year of follow-up. Results A total of 84 COPD patients were enrolled at baseline. Of those, 75 COPD patients completed the first-year of follow-up. We found adverse cumulative effects of particulate matter less than 2.5 μm in aerodynamic diameter (PM2.5), nitrogen dioxide (NO2), sulfur dioxide (SO2) and carbon monoxide (CO) on the forced vital capacity % predicted (FVC % pred) in patients with COPD. Further analyses illustrated that among COPD patients, air pollution exposure was associated with reduced levels of serum eotaxin, interleukin 4 (IL-4) and IL-13 and was correlated with increased serum IL-2, IL-12, IL-17A, interferon γ (IFNγ), monocyte displacing protein 1 (MCP-1) and soluble CD40 ligand (sCD40L). Conclusion Acute exposures to PM2.5, NO2, SO2 and CO were associated with a reduction in FVC % pred in COPD patients. Furthermore, short-term exposure to air pollutants increased systemic inflammation in COPD patients; this may be attributed to increased Th1 and Th17 cytokines and decreased Th2 cytokines.

Parkinson’s disease (PD) is a common neurodegenerative disorder. Rapid eye movement sleep behavior disorder (RBD) is one of the prodromal symptoms of PD. Studies have shown that brain information transmission is affected in PD patients. Consequently, we hypothesized that brain information transmission is impaired in RBD and PD. To prove our hypothesis, we performed functional connectivity (FC) and functional dynamics analysis of three aspects—based on the whole brain, within the resting-state network (RSN), and the interaction between RSNs—using normal control (NC) (n = 21), RBD (n = 24), and PD (n = 45) resting-state functional magnetic resonance imaging (rs-fMRI) data sets. Furthermore, we tested the explanatory power of FC and functional dynamics for the clinical features. Our results found that the global functional dynamics and FC of RBD and PD were impaired. Within RSN, the impairment concentrated in the visual network (VIS) and sensorimotor network (SMN), and the impaired degree of SMN in RBD was higher than that in PD. On the interaction between RSNs, RBD showed a widespread decrease, and PD showed a focal decrease which concentrated in SMN and VIS. Finally, we proved FC and functional dynamics were related to clinical features. These differences confirmed that brain information transmission efficiency and flexibility are impaired in RBD and PD, and these impairments are associated with the clinical features of patients.

BackgroundThrombosis is one of the main complications leading to the failure of autologous arteriovenous fistula (AVF) for patients with renal failure. Thrombectomy is one of the major therapies to remove thrombi to salvage the AVF and prolong its patency.Materials and methodsFifty-six patients with AVF thrombosis at the anastomosis were recruited for this study and underwent thrombectomy procedures. Their clinical variables were collected. The vasculature was accessed at the site of the aneurysmal dilatation. Under ultrasound guidance, a scoop thrombectomy procedure was performed by anterograde and retrograde scooping to remove the thrombus using forceps. Then, a sheath was placed in the direct vertical direction. Angioplasty was performed with a balloon to treat the underlying primary arteriovenous stenosis. Patients were followed up for 12 months after surgery. The procedural success, primary and secondary patency rates, and incidence of procedure-related complications were analyzed.ResultsThere were 2 minor (3.6%) and no major complications. Clinical success was achieved in 55 of the 56 procedures (98.2%). No symptomatic pulmonary embolism or arterial embolization was noted. The primary patency rates at 3, 6, and 12 months were 92.9, 83.8, and 73.3%%, respectively, according to the Kaplan-Meier survival analysis.ConclusionScoop thrombectomy is a safe procedure with high technical success and a low complication rate, and it is an effective method for patients to receive hemodialysis immediately.

Objective. Pretreatment with hydrocortisone (prehydrocortisone) has been used to protect against adverse drug reactions (ADRs) following antivenom administration after snakebite. However, controversial results have been reported in studies evaluating its efficacy. Herein, we conducted a meta-analysis to evaluate the effect of prehydrocortisone on the risk of ADRs. Methods. We conducted a systematic search of PubMed, Embase, and Cochrane for relevant studies on the literature published up to December 6, 2020, with no language restrictions. Premedications, including hydrocortisone with or without other drugs, were compared with placebo or no premedication. Our primary end point was the risk of ADRs, which was reported as the number of patients who developed ADRs divided by the total number of snakebite patients administered with antivenom separately for the prehydrocortisone and control groups for each study. We evaluated pooled data using of a random-effects model. Results. Among 831 identified studies, 4 were eligible and included in our analysis (N = 1348 participants). Upon combining all eight comparisons from the four selected studies, the overall pooled odds ratio (OR) for ADRs was 0.47 (95% CI 0.19, 1.17; p=0.11; I2 = 68%). When the analysis was restricted to only articles using hydrocortisone with other drugs, the pooled OR was 0.19 (95% CI 0.05, 0.75; p=0.02; I2 = 55%). The result was not statistically significant when the analysis was restricted to studies using prehydrocortisone alone, or randomized controlled designs, or cohorts. Our study was limited by heterogeneity, quality, and a paucity of data. Conclusions. The findings in this study revealed that prehydrocortisone alone was ineffective. However, the substantial beneficial effect of prehydrocortisone combinations with premedications (injectable antihistamines or adrenaline) used against ADRs cannot be excluded. Therefore, the use of prehydrocortisone combinations with premedications (injectable antihistamines or adrenaline) as a prophylaxis may reduce the ADRs to antivenom.

Mechanical ventilation is an effective treatment for acute respiratory distress syndrome (ARDS), which can improve the prognosis of ARDS to a certain extent. However, it may further aggravate lung tissue injury, which is defined as ventilator-induced lung injury (VILI). Intermedin (IMD) belongs to the calcitonin gene-related peptide (CPRP) superfamily. Our previous studies have found that IMD reduces the expression proinflammatory cytokines, down-regulates nuclear translocation and improves the integrity of endothelial barrier in ARDS. However, the effect of IMD on VILI has not been clarified. Oxidative stress imbalance and apoptosis are the main pathophysiological characteristics of VILI. In the current study, we used C57B6/J mice and human pulmonary microvascular endothelial cells (HPMECs) to establish a VILI model to analyze the effects of IMD on VILI and explore its potential mechanism. We found that IMD alleviated lung injury and inflammatory response in VILI, mainly in reducing ROS levels, upregulating SOD content, downregulating MDA content, reducing the expression of Bax and caspase-3, and increasing the expression of Bcl-2. In addition, we also found that IMD played its anti-oxidative stress and anti-apoptotic effects via JAK2/STAT3 signaling. Our study may provide some help for the prevention and treatment of VILI.

BackgroundBilateral cerebral palsy (BCP) is the most common type of CP in children and is often accompanied by different degrees of communication impairment. Several studies have attempted to identify children at high risk for communication impairment. However, most prediction factors are qualitative and subjective and may be influenced by rater bias. Individualized objective diagnostic and/or prediction methods are still lacking, and an effective method is urgently needed to guide clinical diagnosis and treatment. The aim of this study is to develop and validate an objective, individual-based model for the prediction of communication impairment in children with BCP by the time they enter school.MethodsA multicenter prospective cohort study will be conducted in four Chinese hospitals. A total of 178 children with BCP will undergo advanced brain magnetic resonance imaging (MRI) at baseline (corrected age, before the age of 2 years). At school entry, communication performance will be assessed by a communication function classification system (CFCS). Three-quarters of children with BCP will be allocated as a training cohort, whereas the remaining children will be allocated as a test cohort. Multivariate lesion- and connectome-based approaches, which have shown good predictive ability of language performance in stroke patients, will be applied to extract features from MR images for each child with BCP. Multiple machine learning models using extracted features to predict communication impairment for each child with BCP will be constructed using data from the training cohort and externally validated using data from the test cohort. Prediction accuracy across models in the test cohort will be statistically compared.DiscussionThe findings of the study may lead to the development of several translational tools that can individually predict communication impairment in children newly diagnosed with BCP to ensure that these children receive early, targeted therapeutic intervention before they begin school.Trial registrationThe study has been registered with the Chinese Clinical Trial Registry (ChiCTR2100049497).

Antibiotic resistance genes (ARGs) are contaminants that can propagate through a variety of environmental media. They contribute to an increase in the number of antibiotic-resistant microbes and thereby pose a danger to human health. Discharge from hospitals is the most significant contributor of ARGs and antibiotic-resistant bacteria to the natural environment. A comprehensive understanding of the microbiological structure and the distribution of ARGs in hospital wastewater can facilitate appropriate treatment of such wastewater and can improve our understanding of the pathophysiology of several epidemic illnesses. In this work, metagenomics techniques were used to compare the microbial species and ARGs in a control group with those in untreated wastewater from three types of hospitals (a general hospital, a hospital of traditional Chinese medicine, and an oral specialty hospital). The microbiota found in the hospital wastewater represented 6,415 species and 244 phyla. The composition of the bacterial community in the wastewater from the three hospitals was significantly different from that in the control group. The ARGs in the samples were also analyzed using the Antibiotic Resistance Genes Database (ARDB) and Comprehensive Antibiotic Resistance Database (CARD). Finally, the link between abundant species and ARGs in the samples was examined. The findings of this study indicate that a connection exists between the microbial species and the ARG composition found in the wastewater samples. A variety of distinct genera of ARGs, each having their own unique correlations, have been found in wastewater from various hospitals. Consequently, the ARGs and microbial species found in the untreated wastewater from various hospitals have unique characteristics. Therefore, more detailed protocols need to be established to treat wastewater from various types of hospitals. Further studies should examine whether a connection exists between the various microbial species found in the wastewater of various types of hospitals and certain illnesses.