Cortical superficial siderosis, hematoma volume, and outcomes after intracerebral hemorrhage: a mediation analysis.

Background: Previous studies have shown that cortical superficial siderosis (cSS) can increase hematoma volume and predict poor outcomes following primary intracerebral hemorrhage (ICH). Objective: We aimed to determine whether a large hematoma volume was the essential factor contributing to worse outcomes of cSS. Methods: Patients with spontaneous ICH underwent a CT scan within 48 h after ictus. Evaluation of cSS was performed using magnetic resonance imaging (MRI) within 7 days. The 90-day outcome was assessed using the modified Rankin Scale (mRS). In addition, we investigated the correlation between cSS, hematoma volume, and 90-day outcomes using multivariate regression and mediation analyses. Results: Among the 673 patients with ICH [mean (SD) age, 61 (13) years; 237 female subjects (35.2%); median (IQR) hematoma volume, 9.0 (3.0-17.6) ml], 131 (19.5%) had cSS. There was an association between cSS and larger hematoma volume (ß = 4.449, 95% CI 1.890-7.009, p < 0.001) independent of hematoma location and was also related to worse 90-day mRS (ß = 0.333, 95% CI 0.008-0.659, p = 0.045) in multivariable regression. In addition, mediation analyses revealed that hematoma volume was an essential factor mediating the effect of cSS on unfavorable 90-day outcomes (proportion mediated:66.04%, p = 0.01). Conclusion: Large hematoma volume was the major charge of directing cSS to worse outcomes in patients with mild to moderate ICH, and cSS was related to a larger hematoma in both lobar and non-lobar areas. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT04803292, identifier: NCT04803292.

Imbalance of Circulating Monocyte Subsets in Subjects with Newly Emerged and Recurrent Hospital-Acquired Pneumonia.

OBJECTIVE: Hospital-acquired pneumonia (HAP) is one of the most common diseases in the intensive care unit, where the development of disease is closely related with the host immune response. Monocytes play an important role in both innate and adaptive immune system. We aimed to investigate the changes of circulating monocyte subsets in subjects with HAP to explore its value in monitoring HAP. METHODS: In total, 60 HAP patients and 18 healthy individuals were enrolled in this study. Human monocyte subsets are classified into 3 groups: nonclassical (NC), intermediate (ITM), and classical (CL). Also, programmed death ligand 1 (PD-L1) expression on circulating monocyte subsets was measured by flow cytometry. RESULTS: Data showed that the ratio of NC, ITM, and CL among monocytes was comparable between HAP patients and healthy controls (P > .05). There was a remarkable imbalance of NC and CL in newly emerged HAP compared to healthy controls (P < .05), subsequently reaching normalization in recurrent HAP (P > .05). Furthermore, although PD-L1 was seemly constitutively expressed by NC, ITM, and CL groups regardless of disease status, it was noted that PD-L1 was dominantly expressed in the CL group (P < .05). CONCLUSION: Given distinct PD-L1 expression, a shift of CL/NC in newly emerged HAP would constitute an inhibitory anti-pathogen immune response. Normalization of circulating monocyte subsets on recurrence of HAP might be the consequence of immune memory of bacterial infection.

Risk Factors and Impact on Outcomes of Lung Cancer Patients Concurrent with Deep Vein Thrombosis.

PURPOSE: Many investigations on prognostic factors in lung cancer have been conducted; however, little is known regarding the outcomes of lung cancer cases complicated by deep vein thrombosis (DVT). This study aimed to determine the risk factors and impact on outcomes of lung cancer patients concurrent with DVT. METHODS: Lung cancer patients who underwent lower-extremity venous ultrasound were enrolled in this study. The patients were divided into a DVT group and a non-DVT group. Demographic information, clinical characteristics, and survival were analyzed by t-test, Wilcoxon test, chi-squared test, and logistic regression analysis. RESULTS: Of the 160 enrolled lung cancer patients, DVT was detected in 30 patients. Among the DVT group, adenocarcinoma was the most common histological type (27/30, 90.00%). Lung cancer complicated with DVT was associated with advanced stage, more severe myocardial injury, and a hypercoagulable state (P < .05). Differences in driver genes between the two groups were not significant. Radiologically, lung cancer patients with DVT were more likely to present with pericardial effusion and pleural effusion than patients without DVT (P < .05). Following multivariable logistic regression analysis, advanced stage (OR 5.368, [95%CI 1.871-18.165], P = .021), NT-proBNP >300 pg/ml (OR 5.575, [95%CI 1.733-3.722], P = .018), D-dimer >5 mg/L (OR 8.449, [95%CI 4.323-18.536], P = .004), CRP >12 mg/L (OR 6.687, [95%CI 1.967-13.617], P = .010), and serum CEA >25 ng/ml (OR 4.755, [95%CI 1.358-3.123], P = .029) were independent risk factors for adenocarcinoma complicated with DVT. Finally, survival analysis revealed that the occurrence of DVT resulted in a poorer prognosis despite anticoagulant therapy (P < .05). CONCLUSION: DVT is a potential complication in patients with lung adenocarcinoma and could represent a prognostic marker for unfavorable outcome. It is essential to screen for DVT in high-risk adenocarcinoma patients.

Risk Factors for Radiological Progression Within Admissive One Week in the Hospitalized COVID-19 Omicron Variant-Infected Patients.

Purpose: Recently, the SARS-CoV-2 Omicron variant was identified as responsible for a novel wave of COVID-19 worldwide. We perform a retrospective study to identify potential risk factors contributing to radiological progression in the COVID-19 patients due to the Omicron variant infection. These findings would provide guiding information for making clinical decisions that could improve the Omicron infection prognosis and reduce disease-related death. Methods: This is a retrospective cohort study from a single center in China. According to the radiological change within admissive one week, enrolled cases were divided into two groups: the progressive (1w-PD) and the stable or improved disease (1w-non-PD). Separate analyses were performed on patients stratified into subgroups using the Mann-Whitney U-test, the Fisher exact test, or the Chi-squared test and a multivariable logistic regression analysis. Results: Both the 1w-non-PD and 1w-PD cohorts displayed comparable asymptomatic infection, have similar underlying disease, impairment in respiratory function, coagulation dysfunction, tissue injury, SARS-CoV-2 viral load, and disease severity. However, the 1w-PD cohort was more inclined to cluster in populations presented with age between 41 and 65, higher CURB-65 scores, undetectable SARS-CoV-2 IgG, and lung affection. Based on the multiple logistic regression analysis, complicated bilateral and ground-glass opacities (GGOs) like pneumonia at admission were independent risk factors to radiological progression within admissive one week. Conclusion: This study provided preliminary data regarding disease progression in Omicron-infected patients that indicated the development of pneumonia in the context of Omicron infection was worthy of potential risk factors.

[Development Scenarios and Environmental Benefits Analysis of Future Power Generation Industry Under Two Modes in China].

In order to study the impact of the "carbon peak and neutrality" mode on future power generation and the environment in China, a Verhulst gray model was established to predict the development of the power generation industry from 2021 to 2060 under the non-"carbon peak and neutrality" mode. In addition, based on the "China 2030 Energy and Power Development Planning Research and 2060 Outlook Report," the development of the power generation industry from 2021 to 2060 under the "carbon peak and neutrality" mode was obtained, and the development scenarios of the future power generation industry in China under two models were compared and studied. The emission factors and emission reduction factors of CO2, SO2, NOx, PM, PM10, and PM2.5 were constructed through the conservation of elements and the generating performance standard, and then four environmental benefits A1-A4 were defined. The results showed that the installed capacity of thermal power will reach the carbon peak in 2026 under the "carbon peak and neutrality" mode. To achieve the carbon neutralization, the installed capacity of thermal power will be reduced by an average of 28 million kilowatts per year after 2026, and the installed capacity of renewable energy generated is required to increase by 154 million kilowatts per year after 2020. Compared with that in the non-"carbon peak and neutrality" mode, the installed capacity of thermal power generation will be greatly reduced, and the installed capacity of renewable energy power generation will be greatly increased under the "carbon peak and neutrality" mode, resulting in huge A1 and A2 environmental benefits. In the next four decades, the cumulative emission reductions in CO2, SO2, NOx, PM, PM10, and PM2.5 thermal power generation A1 are predicted to be 6.64×1010 tons, 1.54×107 tons, 1.55×107 tons, 3.18×106 tons, 1.71×106tons, and 2.23×105 tons, respectively. The cumulative emission reductions of renewable energy power generation A2 will be 5.77×1010 tons, 1.64×107 tons, 1.42×107 tons, 2.86×106 tons, 1.54×106 tons, and 2×105 t tons, respectively. Under the "carbon peak and neutrality" mode, compared with those from coal-fired power generation, the environmental benefits A3 and A4 produced by the relative cleanliness of renewable energy and nuclear power indicated that the cumulative emission reductions (A3+A4) in clean energy power generation of CO2, SO2, NOx, PM, PM10, and PM2.5 in the next four decades will be 3.014×1011 tons, 7.292×107 tons, 7.119×107 tons, 1.454×107 tons, 7.827×106tons, and 1.018×106 tons, respectively.

Intermediate risk pulmonary embolism concomitant with or without lung cancer: a wide spectrum of features.

OBJECTIVES: We aimed to investigate the differences in clinical features between pulmonary embolism (PE) patients concomitant with lung cancer and without lung cancer (LC) and gain further understanding of the impact of lung cancer on pulmonary embolism. METHODS: This retrospective study sampled 114 patients diagnosed with pulmonary embolism from January 2017 to April 2021 in the First Affiliated Hospital of Soochow University. The patients were categorized into the LC group (n = 22) or non-LC group (n = 92). Myocardial injury, coagulation and blood cell parameters, along with imaging findings, were analyzed for the two groups. The primary outcome measure was the 90-day mortality. RESULTS: Of the 114 patients with pulmonary embolism in the present study, the 90 intermediate-risk patients were enrolled for further investigations. Compared to the non-LC group, patients in the LC group had milder myocardial injury, more severe coagulation function disorder, a higher incidence of central PE and a smaller change in diameter of the main pulmonary artery. We found that the occurrence of pericardial effusion created the risk of lung cancer in patients with pulmonary embolism, but there was no increase in the 90-day mortality for non-LC group versus LC group. CONCLUSION: Intermediate risk PE patients concomitant with lung cancer seem to be more likely to present specific clinical features, accordingly, clinicians must pay great attention to PE patients concomitant with lung cancer and implement effective treatments to simultaneously manage the two conditions.

A novel and effective approach to generate germline-like monoclonal antibodies by integration of phage and mammalian cell display platforms.

Phage display technology allows for rapid selection of antibodies from the large repertoire of human antibody fragments displayed on phages. However, antibody fragments should be converted to IgG for biological characterizations and affinity of antibodies obtained from phage display library is frequently not sufficient for efficient use in clinical settings. Here, we describe a new approach that combines phage and mammalian cell display, enabling simultaneous affinity screening of full-length IgG antibodies. Using this strategy, we successfully obtained a novel germline-like anti-TIM-3 monoclonal antibody named m101, which was revealed to be a potent anti-TIM-3 therapeutic monoclonal antibody via in vitro and in vivo experiments, indicating its effectiveness and power. Thus, this platform can help develop new monoclonal antibody therapeutics with high affinity and low immunogenicity.

Association Between Insulin Resistance and Remote Diffusion-Weighted Imaging Lesions in Primary Intracerebral Hemorrhage.

Background: Abnormal glucose metabolism was shown to be associated with the occurrence of remote diffusion-weighted imaging lesions (R-DWILs) after primary intracerebral hemorrhage (ICH) onset. Insulin resistance is a metabolic disorder that was regarded as an indicator of chronic systemic inflammation. In this study, we aimed to determine the effect of insulin resistance on the occurrence of R-DWILs in ICH. Methods: Patients with primary ICH within 14 days after onset were prospectively enrolled from November 2017 to October 2019. R-DWILs was defined as remote focal hyperintensity from the hematoma in DWI, with corresponding hypointensity in apparent diffusion coefficient. The homeostasis model assessment of insulin resistance (HOMA-IR) was used for insulin resistance estimation and calculated as fasting insulin (µU/ml) × fasting glucose (mmol/L)/22.5. Patients in our cohort were divided into four groups according to HOMA-IR index quartiles. Logistic regression analysis and smoothing plots were used to evaluate the association of HOMA-IR with R-DWIL occurrence. Sensitivity analysis was performed in non-diabetic patients, non-obese patients, hypertensive ICH patients, and patients 60 years and older separately. The association between HOMA-IR and systemic inflammatory immune indices neutrophil to lymphocyte ratio (NLR) and monocyte to lymphocyte ratio (MLR) was examined with multiple linear regression analysis. Results: Among the 345 patients, 54 (15.7%) had R-DWILs. Both the third and fourth quartiles of HOMA-IR index were robustly associated with an increased risk of R-DWIL occurrence (adjusted OR 3.58, 95% CI 1.33-9.65; adjusted OR 3.91, 95%CI 1.47-10.41) when compared with the first quartile. The association was consistent in non-diabetic, non-obese, hypertensive ICH patients, as well as in patients 60 years and older. Furthermore, both NLR and MLR were independently associated with HOMA-IR. Conclusions: Our study suggested that insulin resistance evaluated with HOMA-IR index was independently associated with the presence of R-DWILs in patients with acute and subacute primary ICH. It may provide new insights into the metabolism-related brain injury after ICH ictus.

Deep learning for automatically predicting early haematoma expansion in Chinese patients.

BACKGROUND AND PURPOSE: Early haematoma expansion is determinative in predicting outcome of intracerebral haemorrhage (ICH) patients. The aims of this study are to develop a novel prediction model for haematoma expansion by applying deep learning model and validate its prediction accuracy. METHODS: Data of this study were obtained from a prospectively enrolled cohort of patients with primary supratentorial ICH from our centre. We developed a deep learning model to predict haematoma expansion and compared its performance with conventional non-contrast CT (NCCT) markers. To evaluate the predictability of this model, it was also compared with a logistic regression model based on haematoma volume or the BAT score. RESULTS: A total of 266 patients were finally included for analysis, and 74 (27.8%) of them experienced early haematoma expansion. The deep learning model exhibited highest C statistic as 0.80, compared with 0.64, 0.65, 0.51, 0.58 and 0.55 for hypodensities, black hole sign, blend sign, fluid level and irregular shape, respectively. While the C statistics for swirl sign (0.70; p=0.211) and heterogenous density (0.70; p=0.141) were not significantly higher than that of the deep learning model. Moreover, the predictive value for the deep learning model was significantly superior to that of the logistic model of haematoma volume (0.62; p=0.042) and the BAT score (0.65; p=0.042). CONCLUSIONS: Compared with the conventional NCCT markers and BAT predictive model, the deep learning algorithm showed superiority for predicting early haematoma expansion in ICH patients.

Characterization of a Type VI Secretion System vgrG2 Gene in the Pathogenicity of Burkholderia thailandensis BPM.

Burkholderia thailandensis is a clinically underestimated conditional pathogen in the genus Burkholderia, the pathogenicity of the infection caused by B. thailandensis remains poorly understood. According to previous studies, Type-VI secretion system (T6SS) is a protein secreting device widely existing in Gram-negative bacilli. Valine-glycine repeat protein G (VgrG) is not only an important component of T6SS, but also a virulence factor of many Gram-negative bacilli. In one of our previous studies, a unique T6SS vgrG gene (vgrG2 gene) was present in a virulent B. thailandensis strain BPM (BPM), but not in the relatively avirulent B. thailandensis strain E264 (E264). Meanwhile, transcriptome analysis of BPM and E264 showed that the vgrG2 gene was strongly expressed in BPM, but not in E264. Therefore, we identified the function of the vgrG2 gene by constructing the mutant and complemented strains in this study. In vitro, the vgrG2 gene was observed to be involved in the interactions with host cells. The animal model experiment showed that the deletion of vgrG2 gene significantly led to the decrease in the lethality of BPM and impaired its ability to trigger host immune response. In conclusion, our study provides a new perspective for studying the pathogenicity of B. thailandensis and lays the foundation for discovering the potential T6SS effectors.

Population genetic analysis reveals cryptic sex in the phytopathogenic fungus Alternaria alternata.

Reproductive mode can impact population genetic dynamics and evolutionary landscape of plant pathogens as well as on disease epidemiology and management. In this study, we monitored the spatial dynamics and mating type idiomorphs in ~700 Alternaria alternata isolates sampled from the main potato production areas in China to infer the mating system of potato early blight. Consistent with the expectation of asexual species, identical genotypes were recovered from different locations separated by hundreds of kilometers of geographic distance and spanned across many years. However, high genotype diversity, equal MAT1-1 and MAT1-2 frequencies within and among populations, no genetic differentiation and phylogenetic association between two mating types, combined with random association amongst neutral markers in some field populations, suggested that sexual reproduction may also play an important role in the epidemics and evolution of the pathogen in at least half of the populations assayed despite the fact that no teleomorphs have been observed yet naturally or artificially. Our results indicated that A. alternata may adopt an epidemic mode of reproduction by combining many cycles of asexual propagation with fewer cycles of sexual reproduction, facilitating its adaptation to changing environments and making the disease management on potato fields even more difficult.

[Preparation and Photocatalytic Properties of Supported TiO2 Photocatalytic Material].

Titanium dioxide (TiO2) supported on spherical alumina substrate was prepared by using sol-gel method combined with dip-coating process. The surface morphology and structure of the synthesized samples were characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD) pattern. The results show that the morphology of the supported TiO2 composite material was obviously different from that of the original support. It reveals a layer formed by anatase TiO2 nanoparticles of 10-20 nm was deposited on the alumina substrate. Energy dispersive X-ray spectroscopy (EDX) analyses on the spherical alumina substrate and the resulting TiO2 composite catalyst were performed to determine the TiO2 loading content in the samples. It indicates that the TiO2 loading content on alumina substrate could be effectively increased by increasing the times of dip-coating alumina support in TiO2 sol. When dip-coating times increased to 5, the TiO2 loading content increased from 3.8 Wt. % to 15.7 Wt. %. In addition, the photocatalytic performances of the supported TiO2 materials prepared by different dip-coating times have been investigated by degrading methylene blue. It was found that the surface morphology of the supported TiO2 material was not only improved, but also the photocatalytic activity could be promoted significantly by increasing the dip-coating times. When the alumina substrate was dip-coated in TiO2 sol from 1 to 4 times, the degradation rate of methylene blue increased from 40% to 83.1%. However, after dip-coating the alumina support in TiO2 sol for 5 times, the degradation of methylene blue was only up to 85.6%. This indicates that the photocatalytic activity increased slowly when the TiO2 content in the supported catalyst was up to some extent. It is attributed to the continuous dip-coating resulted in less opportunities and weak intensity of illumination for the TiO2 nano-particles that under lower layer. The photocatalytic activity was relatively stable after repeated use of the supported TiO2 material for 5 times.