The bacterial and fungal profiles of patients hospitalized with non-COVID-19 lower respiratory tract infections in Wuhan, China, 2019-2021.

AIMS: A severe lockdown occurred in Wuhan during the COVID-19 pandemic, followed by a remission phase in the pandemic's aftermath. This study analyzed the bacterial and fungal profiles of respiratory pathogens in patients hospitalized with non-COVID-19 lower respiratory tract infections (LRTI) during this period to determine the pathogen profile distributions in different age groups and hospital departments in Wuhan. METHODS AND RESULTS: We collected reports of pathogen testing in the medical records of patients hospitalized with non-COVID-19 LRTI between 2019 and 2021. These cases were tested for bacterial and fungal pathogens using 16S and internal transcribed spacer sequencing methods on bronchoalveolar lavage fluid samples. The study included 1368 cases. The bacteria most commonly identified were Streptococcus pneumoniae (12.50%) and Mycoplasma pneumoniae (8.33%). The most commonly identified fungi were Aspergillus fumigatus (2.49%) and Pneumocystis jirovecii (1.75%). Compared to 2019, the S. pneumoniae detection rates increased significantly in 2021, and those of M. pneumoniae decreased. S. pneumoniae was detected mainly in children. The detection rates of almost all fungi were greater in the respiratory Intensive Care Unit compared to respiratory medicine. S. pneumoniae and M. pneumoniae were detected more frequently in the pediatric department. CONCLUSIONS: Before and after the COVID-19 outbreak, a change in the common pathogen spectrum was detected in patients with non-COVID-19 in Wuhan, with the greatest change occurring among children. The major pathogens varied by the patient's age and the hospital department.

Current state and influencing factors in airbag management among emergency department nurses: A multicenter study.

BACKGROUND: The emergency department (ED) plays a critical role in establishing artificial airways and implementing mechanical ventilation. Managing airbags in the ED presents a prime opportunity to mitigate the risk of ventilator-associated pneumonia. Nonetheless, existing research has largely overlooked the understanding, beliefs, and practical dimensions of airway airbag management among ED nurses, with a predominant focus on intensive care unit nurses. AIM: To investigate the current status of ED nurses' knowledge, beliefs, and practical behaviors in airway airbag management and their influencing factors. METHODS: A survey was conducted from July 10th to August 10th, 2023, using convenience sampling on 520 ED nurses from 15 tertiary hospitals and 5 sary hospitals in Shanghai. Pathway analysis was utilized to analyze the influencing factors. RESULTS: The scores for ED nurses' airway airbag management knowledge were 60.26 ± 23.00, belief was 88.65 ± 13.36, and behavior was 75.10 ± 19.84. The main influencing factors of airbag management knowledge included participation in specialized nurse or mechanical ventilation training, department, and work experience in the department. Influencing factors of airbag management belief comprised knowledge, department, and participation in specialized nurse or mechanical ventilation training. Primary influencing factors of airbag management behavior included knowledge, belief, department, participation in specialized nurse or mechanical ventilation training, and professional title. The belief in airbag management among ED nurses acted as a partial mediator between knowledge and behavior, with a total effect value of 0.513, and an indirect effect of 0.085, constituting 16.6% of the total effect. CONCLUSION: ED nurses exhibit a positive attitude toward airbag management with relatively standardized practices, yet there remains room for improvement in their knowledge levels. Nursing managers should implement interventions tailored to the characteristics of ED nurses' airbag management knowledge, beliefs, and practices to enhance their airbag management proficiency.

The etiological diagnostic value of metagenomic next-generation sequencing in suspected community-acquired pneumonia.

BACKGROUND: The emergence of metagenomic next-generation sequencing (mNGS) may provide a promising tool for early and comprehensive identification of the causative pathogen in community-acquired pneumonia (CAP). In this study, we aim to further evaluate the etiological diagnostic value of mNGS in suspected CAP. METHODS: A total of 555 bronchoalveolar lavage fluid (BALF) samples were collected for pathogen detection by mNGS from 541 patients with suspected CAP. The clinical value was assessed based on infection diagnosis and treatment guidance. The diagnostic performance for pathogen identification by mNGS and sputum culture and for tuberculosis (TB) by mNGS and X-pert MTB/RIF were compared. To evaluate the potential for treatment guidance, we analyzed the treatment regimen of patients with suspected CAP, including imaging changes of lung after empirical antibacterial therapy, intensified regimen, antifungal treatment, and a 1-year follow up for patients with unconfirmed diagnosis and non-improvement imaging after anti-infective treatment and patients with high suspicion of TB or NTM infection who were transferred to the Wuhan Pulmonary Hospital for further diagnosis and even anti-mycobacterium therapy. RESULTS: Of the 516 BALF samples that were analyzed by both mNGS and sputum culture, the positivity rate of mNGS was significantly higher than that of sputum culture (79.1% vs. 11.4%, P = 0.001). A total of 48 samples from patients with confirmed TB were analyzed by both mNGS and X-pert MTB/RIF, and the sensitivity of mNGS for the diagnosis of active TB was significantly lower than that of X-pert MTB/RIF (64.6% vs. 85.4%, P = 0.031). Of the 106 pathogen-negative cases, 48 were ultimately considered non-infectious diseases, with a negative predictive value of 45.3%. Of the 381 pathogen-positive cases, 311 were eventually diagnosed as CAP, with a positive predictive value of 81.6%. A total of 487 patients were included in the evaluation of the therapeutic effect, and 67.1% improved with initial empirical antibiotic treatment. Of the 163 patients in which bacteria were detected, 77.9% improved with antibacterial therapy; of the 85 patients in which fungi were detected, 12.9% achieved remission after antifungal therapy. CONCLUSIONS: Overall, mNGS had unique advantages in the detection of suspected CAP pathogens. However, mNGS was not superior to X-pert MTB/RIF for the diagnosis of TB. In addition, mNGS was not necessary as a routine test for all patients admitted with suspected CAP. Furthermore, when fungi are detected by mNGS, antifungal therapy should be cautious.

Toxin genotypes, antibiotic resistance and their correlations in Clostridioides difficile isolated from hospitals in Xi'an, China.

BACKGROUND: Clostridioides difficile is the main pathogen of antimicrobial-associated diarrhoea and health care facility-associated infectious diarrhoea. This study aimed to investigate the prevalence, toxin genotypes, and antibiotic resistance of C. difficile among hospitalized patients in Xi'an, China. RESULTS: We isolated and cultured 156 strains of C. difficile, representing 12.67% of the 1231 inpatient stool samples collected. Among the isolates, tcdA + B + strains were predominant, accounting for 78.2% (122/156), followed by 27 tcdA-B + strains (27/156, 17.3%) and 6 binary toxin gene-positive strains. The positive rates of three regulatory genes, tcdC, tcdR, and tcdE, were 89.1% (139/156), 96.8% (151/156), and 100%, respectively. All isolates were sensitive to metronidazole, and the resistance rates to clindamycin and cephalosporins were also high. Six strains were found to be resistant to vancomycin. CONCLUSION: Currently, the prevalence rate of C. difficile infection (CDI) in Xi'an is 12.67% (156/1231), with the major toxin genotype of the isolates being tcdA + tcdB + cdtA-/B-. Metronidazole and vancomycin were still effective drugs for the treatment of CDI, but we should pay attention to antibiotic management and epidemiological surveillance of CDI.

scMoresDB: A comprehensive database of single-cell multi-omics data for human respiratory system.

The human respiratory system is a complex and important system that can suffer a variety of diseases. Single-cell sequencing technologies, applied in many respiratory disease studies, have enhanced our ability in characterizing molecular and phenotypic features at a single-cell resolution. The exponentially increasing data from these studies have consequently led to difficulties in data sharing and analysis. Here, we present scMoresDB, a single-cell multi-omics database platform with extensive omics types tailored for human respiratory diseases. scMoresDB re-analyzes single-cell multi-omics datasets, providing a user-friendly interface with cross-omics search capabilities, interactive visualizations, and analytical tools for comprehensive data sharing and integrative analysis. Our example applications highlight the potential significance of BSG receptor in SARS-CoV-2 infection as well as the involvement of HHIP and TGFB2 in the development and progression of chronic obstructive pulmonary disease. scMoresDB significantly increases accessibility and utility of single-cell data relevant to human respiratory system and associated diseases.

A clinical consensus-compliant deep learning approach to quantitatively evaluate human in vitro fertilization early embryonic development with optical microscope images.

The selection of embryos is a key for the success of in vitro fertilization (IVF). However, automatic quality assessment on human IVF embryos with optical microscope images is still challenging. In this study, we developed a clinical consensus-compliant deep learning approach, named Esava (Embryo Segmentation and Viability Assessment), to quantitatively evaluate the development of IVF embryos using optical microscope images. In total 551 optical microscope images of human IVF embryos of day-2 to day-3 were collected, preprocessed, and annotated. Using the Faster R-CNN model as baseline, our Esava model was constructed, refined, trained, and validated for precise and robust blastomere detection. A novel algorithm Crowd-NMS was proposed and employed in Esava to enhance the object detection and to precisely quantify the embryonic cells and their size uniformity. Additionally, an innovative GrabCut-based unsupervised module was integrated for the segmentation of blastomeres and embryos. Independently tested on 94 embryo images for blastomere detection, Esava obtained the high rates of 0.9940, 0.9121, and 0.9531 for precision, recall, and mAP respectively, and gained significant advances compared with previous computational methods. Intraclass correlation coefficients indicated the consistency between Esava and three experienced embryologists. Another test on 51 extra images demonstrated that Esava surpassed other tools significantly, achieving the highest average precision 0.9025. Moreover, it also accurately identified the borders of blastomeres with mIoU over 0.88 on the independent testing dataset. Esava is compliant with the Istanbul clinical consensus and compatible to senior embryologists. Taken together, Esava improves the accuracy and efficiency of embryonic development assessment with optical microscope images.

Clinical and functional characterization of rare compound heterozygous mutations in the SERPINC1 gene causing severe thrombophilia.

INTRODUCTION: Hereditary antithrombin (AT) deficiency is a rare autosomal dominant disorder with significant clinical heterogeneity. In the study, we identified a patient with AT deficiency caused by compound heterozygous mutations in the SERPINC1 gene. METHODS: A total of 9 individuals from three generations were investigated. The mutations were identified by direct sequencing of SERPINC1. Multiple in silico tools were programmed to predict the conservation of mutations and the effect on the AT structure. The coagulation state was evaluated by the thrombin generation assay. Recombinant AT was overexpressed in HEK293T cells; the mRNA level was determined using RT-qPCR. Western blotting, ELISA, and immunocytofluorescence were applied to characterize the recombinant AT protein. RESULTS: The proband was a 26-year-old male who experienced recurrent venous thrombosis. He presented the type I deficiency with 33 % AT activity and a synchronized decrease in AT antigen. Genetic screening revealed that he carried a heterozygous c.318_319insT (p.Asn107*) in exon 2 and a heterozygous c.922G > T (p.Gly308Cys) in exon 5, both of which were completely conserved in homologous species and resulted in enhanced thrombin generation capability. Hydrophobicity analysis suggested that the p.Gly308Cys mutation may interfere with the hydrophobic state of residues 307-313. In vitro expression studies indicated that the levels of the recombinant protein AT-G308C decreased to 46.98 % ± 2.94 % and 41.35 % ± 1.48 % in transfected cell lysates and media, respectively. After treatment with a proteasome inhibitor (MG132), the quantity of AT-G308C protein in the cytoplasm was replenished to a level comparable to that of the wild type. The mRNA level of AT-N107* was significantly reduced and the recombinant protein AT-N107* was not detected in either the lysate or the culture media. CONCLUSION: These two mutations were responsible for the AT defects and clinical phenotypes of the proband. The p.Gly308Cys mutation could lead to proteasome-dependent degradation of the AT protein in the cytoplasm by altering local residue hydrophobicity. The c.318_319insT could eliminate aberrant transcripts by triggering nonsense-mediated mRNA degradation. Both mutations resulted in type I AT deficiency.

Cross-cultural adaptation and validation for central sensitization inventory: based on Chinese patients undergoing total knee arthroplasty for knee osteoarthritis.

BACKGROUND: This study was conducted to develop a simplified Chinese version of the central sensitization inventory (CSI-CV) and to evaluate its reliability and validity. METHODS: The CSI-CV was developed through a process involving the translation and back translation of the original CSI. Subsequently, experts reviewed and revised the content of the items to ensure their appropriateness. A total of 325 patients with knee osteoarthritis (KOA), who were scheduled to undergo total knee arthroplasty (TKA), completed the CSI-CV at a prominent orthopedic center in Xi'an, China. Afterward, a random selection of 100 participants was chosen for retesting after one week. The reliability and validity of the inventory were evaluated through exploratory factor analysis, correlation coefficient calculation and other methods. RESULTS: The CSI-CV consists of 25 items in five dimensions (emotional distress, headache and jaw symptoms, physical symptoms, urological symptoms, and fatigue and sleep problems). The cumulative variance contribution rate was 75.3%, the Cronbach's α coefficient was 0.83, the Guttman split-half reliability coefficient was 0.88 and the intraclass correlation coefficient was 0.965. The CSI-CV scores correlated moderately with the total scores of the brief pain inventory (r = 0.506), Western Ontario and McMaster Universities Osteoarthritis Index (r = 0.466) and EuroQoL Group's five-dimension questionnaire (r = 0.576). CONCLUSIONS: The findings demonstrate that the CSI was successfully trans-culturally adapted into a simplified Chinese version (CSI-CV) that was reliable and valid for Chinese-speaking patients who awaiting TKA for KOA.

The changing pattern of common respiratory viruses among children from 2018 to 2021 in Wuhan, China.

BACKGROUND: Acute respiratory infections in children are a global public health challenge. Owing to the coronavirus disease (COVID-19) pandemic, non-pharmaceutical interventions, including patient isolation, social distancing, hand washing, and mask wearing, have been widely implemented, impacting the transmission of common respiratory viruses. The aim of this study was to clarify the epidemiological features of respiratory viruses in children less than 14 years of age in Wuhan before and after COVID-19. METHODS: Respiratory specimens were collected from patients aged < 14 years at two hospitals in Wuhan, China, from January 2018 to December 2021. Seven respiratory viruses were identified using an immunofluorescence assay. Pathogen profiles and seasonality were analysed. RESULTS: The number of visits and virus detection rate decreased dramatically after February 2020. The respiratory virus detection rate peaked in January and December and decreased dramatically in February and August. The detection rate was lower in 2021 than in 2018 and 2019. Respiratory syncytial virus (RSV) was identified as the leading pathogen in children aged < 1 year and 1-4 years before and after the COVID-19 pandemic. In children aged 5-14 years, influenza virus was detected at the highest rate before, and RSV after, the COVID-19 pandemic. RSV was the most common virus in coinfections. CONCLUSIONS: This study revealed the epidemiological patterns of common respiratory viruses from 2018 to 2021. The spectrum of pathogens involved in paediatric respiratory infections had partly changed. Non-pharmaceutical interventions resulted in fewer opportunities for the spread of common viruses but also in an "immunity debt" that could have negative consequences when the pandemic is under control in Wuhan.

Multi-omic analysis characterizes molecular susceptibility of receptors to SARS-CoV-2 spike protein.

In the post COVID-19 era, new SARS-CoV-2 variant strains may continue emerging and long COVID is poised to be another public health challenge. Deciphering the molecular susceptibility of receptors to SARS-CoV-2 spike protein is critical for understanding the immune responses in COVID-19 and the rationale of multi-organ injuries. Currently, such systematic exploration remains limited. Here, we conduct multi-omic analysis of protein binding affinities, transcriptomic expressions, and single-cell atlases to characterize the molecular susceptibility of receptors to SARS-CoV-2 spike protein. Initial affinity analysis explains the domination of delta and omicron variants and demonstrates the strongest affinities between BSG (CD147) receptor and most variants. Further transcriptomic data analysis on 4100 experimental samples and single-cell atlases of 1.4 million cells suggest the potential involvement of BSG in multi-organ injuries and long COVID, and explain the high prevalence of COVID-19 in elders as well as the different risks for patients with underlying diseases. Correlation analysis validated moderate associations between BSG and viral RNA abundance in multiple cell types. Moreover, similar patterns were observed in primates and validated in proteomic expressions. Overall, our findings implicate important therapeutic targets for the development of receptor-specific vaccines and drugs for COVID-19.

Protective effect and mechanism of styrax on ischemic stroke rats: metabonomic insights by UPLC-Q/TOF-MS analysis.

CONTEXT: Styrax is used for prevention and treatment of cerebrovascular diseases. However, the underlying mechanism remains unclear. OBJECTIVE: To elucidate styrax's anti-ischemic stroke protective effects and underlying mechanisms. MATERIALS AND METHODS: An ischemic-stroke rat model was established based on middle cerebral artery occlusion (MCAO). Sprague-Dawley rats were randomly assigned to the following groups (n = 10) and administered intragastrically once a day for 7 consecutive days: sham, model, nimodipine (24 mg/kg), styrax-L (0.1 g/kg), styrax-M (0.2 g/kg) and styrax-H (0.4 g/kg). Neurological function, biochemical assessment, and ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS)-based serum metabonomics were used to elucidate styrax's cerebral protective effects and mechanisms. Pearson correlation and western blot analyses were performed to verify. RESULTS: The addition of 0.4 g/kg styrax significantly reduced cerebral infarct volume and neurobehavioral abnormality score. Different doses of styrax also decrease MDA, TNF-α, IL-6, and IL-1ß, and increase SOD and GSH-Px in ischemic-stroke rats (p < 0.05; MDA, p < 0.05 only at 0.4 g/kg dose). Biochemical indicators and metabolic-profile analyses (PCA, PLS-DA, and OPLS-DA) also supported styrax's protective effects. Endogenous metabolites (22) were identified in ischemic-stroke rats, and these perturbations were reversible via styrax intervention, which is predominantly involved in energy metabolism, glutathione and glutamine metabolism, and other metabolic processes. Additionally, styrax significantly upregulated phosphorylated AMP-activated protein kinase and glutaminase brain-tissue expression. CONCLUSION: Styrax treatment could ameliorate ischemic-stroke rats by intervening with energy metabolism and glutamine metabolism. This can help us understand the mechanism of styrax, inspiring more clinical application and promotion.

Enhanced photocatalytic activity of magnetically recyclable spherical Fe3O4/Cu2O S-scheme heterojunction.

In this study, magnetically recyclable spherical Fe3O4/Cu2O particles comprising S-scheme heterojunctions were prepared by a simple hydrothermal approach using n-type semiconductor Fe3O4 as precursor and p-type semiconductor Cu2O. A Fenton-like system was thus constructed via the addition to Fe3O4/Cu2O of hydrogen peroxide. A rhodamine B (RhB) solution was used to simulate polluted wastewater, and photocatalytic RhB removal experiments were conducted under visible light irradiation. Powder X-ray diffractometry, vibrating-sample magnetometry, nitrogen adsorption-desorption, transmission electron microscopy, and X-ray photoelectron spectroscopy experiments were conducted to characterise Fe3O4 and Fe3O4/Cu2O composite. The band gap of Fe3O4/Cu2O was 1.76 eV, narrower than that of Fe3O4 (2.14 eV). The effects of the pH, sample dosage, hydrogen peroxide concentration, and RhB initial concentration on RhB removal were investigated. According to evidence, under the optimum reaction conditions, the RhB removal rate was 99.4%. The Fe3O4/Cu2O composite exhibited good photocatalytic efficacy even after four cycles of testing. Based on the results of free radical capture experiments, hydroxyl radicals and holes cooperated as main reactive species in the photocatalytic system. The Fe3O4/Cu2O photocatalyst can be easily removed based on magnetism, and it has been proven to be very effective for the degradation of RhB under both UV and visible light irradiation.

Development and validation of the patient reported outcomes questionnaire of children with asthma in China: A Caregiver's proxy-reported measure.

Background: Research on asthma control levels and quality of life is essential for children with asthma during their growth stage. Therefore, it is necessary to develop a questionnaire that can be used for monitoring and evaluating the disease control effectiveness and quality of life of children with asthma in China and to conduct a preliminary evaluation for its reliability, validity, and discriminative ability. Methods: The questionnaire was created through a literature review and qualitative interviews for a targeted population. Based on the previous work, 30 caregivers of children with asthma and 5 experienced pediatricians reviewed and discussed a collection of items. Then, 72 items were screened and selected to form the draft questionnaire. After three rounds of investigation (with 240, 503, and 360 participants, respectively), the final questionnaire was established according to the evaluation results. The structure of the questionnaire was explored through confirmatory factor analysis. Exploratory factor analysis and variability analysis were applied based on the first two rounds of investigation. Reliability, construct validity, and discriminative ability were evaluated based on the third round of investigation. Results: The questionnaire contains 6 dimensions and 34 items, and the total cumulative variance contribution rate was 54.96%; Cronbach's α coefficient was 0.91; the split-half reliability coefficient was 0.75, and the test-retest reliability coefficient was 0.74. The children's age, gender, residence, asthma attack in the last three months, caregivers' education background, and monthly income per caregiver were correlated with patient-reported outcomes of children with asthma. Conclusion: The questionnaire appeared to have good reliability, construct validity, and discriminative ability in children with asthma in China.

Analysis of a machine learning-based risk stratification scheme for acute kidney injury in vancomycin.

Vancomycin-associated acute kidney injury (AKI) continues to pose a major challenge to both patients and healthcare providers. The purpose of this study is to construct a machine learning framework for stratified predicting and interpreting vancomycin-associated AKI. Our study is a retrospective analysis of medical records of 724 patients who have received vancomycin therapy from 1 January 2015 through 30 September 2020. The basic clinical information, vancomycin dosage and days, comorbidities and medication, laboratory indicators of the patients were recorded. Machine learning algorithm of XGBoost was used to construct a series risk prediction model for vancomycin-associated AKI in different underlying diseases. The vast majority of sub-model performed best on the corresponding sub-dataset. Additionally, the aim of this study was to explain each model and to explore the influence of clinical variables on prediction. As the results of the analysis showed that in addition to the common indicators (serum creatinine and creatinine clearance rate), some other underappreciated indicators such as serum cystatin and cumulative days of vancomycin administration, weight and age, neutrophils and hemoglobin were the risk factors for cancer, diabetes mellitus, heptic insufficiency respectively. Stratified analysis of the comorbidities in patients with vancomycin-associated AKI further confirmed the necessity for different patient populations to be studied.

Estimating and validating the structure of feeding behavior networks.

PURPOSE: Network analysis has been widely used in psychometrics over the past decade, yet it is unknown that whether this methodology could be applied in the field of child health assessment such as caregivers' feeding behavior and child eating behavior. Our study leveraged network psychometrics method to estimating and examining the network structure of Chinese Preschoolers' Caregivers' Feeding Behavior Scale (CPCFBS), and compared the applicability of network methods in the feeding behavior scale. METHODS: The CPCFBS was previously applied in a sample of 768 preschoolers' caregivers, used to estimate the structure of feeding behavior networks. Network structure was estimated with Gaussian Graphical Model. Dimensionality was detected using Exploratory Graph Analysis (EGA). The network structural consistency was tested using EGA bootstrap. The network structure was compared with the original structure using model fit indices and reliability. RESULTS: A seven-dimensional EGA network was explored after rearranging four items and deleting one item with unstable structural consistency. The absolute fit and relative fit of EGA structure were better than the original structure. The EGA structure had nearly same values of the reliability with the original structure. CONCLUSION: Our study presented a novel perspective for feeding behavior analytical strategies, and demonstrated that network analysis was applicable and superior in exploring the structure of feeding behavior scales. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

D-dimer levels and characteristics of lymphocyte subsets, cytokine profiles in peripheral blood of patients with severe COVID-19: A systematic review and meta-analysis.

Purpose: A series of complications caused by severe COVID-19 can significantly affect short-term results. Therefore, early diagnosis is essential for critically COVID-19 patients. we aimed to investigate the correlation among D-dimer levels, lymphocyte subsets, cytokines, and disease severity in COVID-19 patients. Methods: Systematic review and meta- analysis of PubMed, Scopus, Web of Science, Cochrane Central Register of Controlled Trials, Embase, clinical trials, and China National Knowledge Infrastructure (CNKI) until 1 August 2022. We considered case-control, and cohort studies that compared laboratory parameters between patients with severe or non-serious diseases or between survivors and non-survivors. Pooled data was assessed by use of a random-effects model and used I 2 to test heterogeneity. We assessed the risk of bias using the Newcastle- Ottawa Scale. Results: Of the 5,561 identified studies, 32 were eligible and included in our analysis (N = 3,337 participants). Random-effect results indicated that patients with COVID-19 in severe group had higher levels for D-dimer (WMD = 1.217 mg/L, 95%CI=[0.788, 1.646], P < 0.001), neutrophil-to-lymphocyte ratio (NLR) (WMD = 6.939, 95%CI = [4.581, 9.297], P < 0.001), IL-2 (WMD = 0.371 pg/ml, 95%CI = [-0.190, 0.932], P = 0.004), IL-4 (WMD = 0.139 pg/ml, 95%CI = [0.060, 0.219], P = 0.717), IL-6 (WMD = 44.251 pg/ml, 95%CI = [27.010, 61.493], P < 0.001), IL-10 (WMD = 3.718 pg/ml, 95%CI = [2.648, 4.788], P < 0.001) as well as lower levels of lymphocytes (WMD = -0.468( × 109/L), 95%CI = [-0.543, -0.394], P < 0.001), T cells (WMD = -446.746(/µL), 95%CI = [-619.607, -273.885], P < 0.001), B cells (WMD = -60.616(/µL), 95%CI = [-96.452, -24.780], P < 0.001), NK cells (WMD = -68.297(/µL), 95%CI = [-90.600, -45.994], P < 0.001), CD3+T cells (WMD = -487.870(/µL), 95%CI = [-627.248, -348.492], P < 0.001), CD4+T cells (WMD = -290.134(/µL), 95%CI = [-370.834, -209.435], P < 0.001), CD8+T cells (WMD = -188.781(/µL), 95%CI = [-227.806, -149.757], P < 0.001). Conclusions: There is a correlation among higher levels of D-dimer, cytokines, lower levels of lymphocyte subsets, and disease severity in COVID-19 patients. These effective biomarkers may help clinicians to evaluate the severity and prognosis of COVID-19. This study is registered with PROSPERO, number CRD42020196659. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=196659; PROSPERO registration number: CRD42020196659.

Identification of a cytokine-dominated immunosuppressive class in squamous cell lung carcinoma with implications for immunotherapy resistance.

BACKGROUND: Immune checkpoint blockade (ICB) therapy has revolutionized the treatment of lung squamous cell carcinoma (LUSC). However, a significant proportion of patients with high tumour PD-L1 expression remain resistant to immune checkpoint inhibitors. To understand the underlying resistance mechanisms, characterization of the immunosuppressive tumour microenvironment and identification of biomarkers to predict resistance in patients are urgently needed. METHODS: Our study retrospectively analysed RNA sequencing data of 624 LUSC samples. We analysed gene expression patterns from tumour microenvironment by unsupervised clustering. We correlated the expression patterns with a set of T cell exhaustion signatures, immunosuppressive cells, clinical characteristics, and immunotherapeutic responses. Internal and external testing datasets were used to validate the presence of exhausted immune status. RESULTS: Approximately 28 to 36% of LUSC patients were found to exhibit significant enrichments of T cell exhaustion signatures, high fraction of immunosuppressive cells (M2 macrophage and CD4 Treg), co-upregulation of 9 inhibitory checkpoints (CTLA4, PDCD1, LAG3, BTLA, TIGIT, HAVCR2, IDO1, SIGLEC7, and VISTA), and enhanced expression of anti-inflammatory cytokines (e.g. TGFß and CCL18). We defined this immunosuppressive group of patients as exhausted immune class (EIC). Although EIC showed a high density of tumour-infiltrating lymphocytes, these were associated with poor prognosis. EIC had relatively elevated PD-L1 expression, but showed potential resistance to ICB therapy. The signature of 167 genes for EIC prediction was significantly enriched in melanoma patients with ICB therapy resistance. EIC was characterized by a lower chromosomal alteration burden and a unique methylation pattern. We developed a web application ( http://lilab2.sysu.edu.cn/tex & http://liwzlab.cn/tex ) for researchers to further investigate potential association of ICB resistance based on our multi-omics analysis data. CONCLUSIONS: We introduced a novel LUSC immunosuppressive class which expressed high PD-L1 but showed potential resistance to ICB therapy. This comprehensive characterization of immunosuppressive tumour microenvironment in LUSC provided new insights for further exploration of resistance mechanisms and optimization of immunotherapy strategies.

Immunocytes Rapid Responses Post-ischemic Stroke in Peripheral Blood in Patients With Different Ages.

Objectives: To explore the alterations in immune cell composition in peripheral blood in patients with acute ischemic stroke (AIS) based on their age group. Methods: Patients with imaging confirmed AIS were enrolled from April 2019 to January 2020 and were divided into three groups according to their ages: <55 years (group-A), 55-65 years (group-B), and >65 years (group-C). Blood samples were collected immediately when the patients were admitted to our ward prior to any intervention. Flow cytometry was used to analyze immune cell composition in peripheral blood. Results: A total of 41 eligible patients were included for final analysis. Among the three groups, the proportions of CD56+ CD16dim NK cells were least to greatest in group-B, group-A, then group-C, respectively. With increasing age, there was a decrease in the proportion of CD3+ T-cells (group-A vs. group-C, P = 0.016) and CD3+CD4+ T-cells (group-C vs. group-A, P = 0.008; group-C vs. group-B P = 0.026). Meanwhile, no significant differences in proportions of monocytes and B cells were observed. Conclusions: The compositions of immune cells in peripheral blood of AIS patients were distinct when divided by age groups. Differences in immune cell ratios may affect clinical outcomes and foreshadows possible need for customized treatment of AIS in different age groups.

Cytokine storm promoting T cell exhaustion in severe COVID-19 revealed by single cell sequencing data analysis.

Background: Evidence has suggested that cytokine storms may be associated with T cell exhaustion (TEX) in COVID-19. However, the interaction mechanism between cytokine storms and TEX remains unclear. Methods: With the aim of dissecting the molecular relationship of cytokine storms and TEX through single-cell RNA sequencing data analysis, we identified 14 cell types from bronchoalveolar lavage fluid of COVID-19 patients and healthy people. We observed a novel subset of severely exhausted CD8 T cells (Exh T_CD8) that co-expressed multiple inhibitory receptors, and two macrophage subclasses that were the main source of cytokine storms in bronchoalveolar. Results: Correlation analysis between cytokine storm level and TEX level suggested that cytokine storms likely promoted TEX in severe COVID-19. Cell-cell communication analysis indicated that cytokines (e.g. CXCL10, CXCL11, CXCL2, CCL2, and CCL3) released by macrophages acted as ligands and significantly interacted with inhibitory receptors (e.g. CXCR3, DPP4, CCR1, CCR2, and CCR5) expressed by Exh T_CD8. These interactions formed the cytokine-receptor axes, which were also verified to be significantly correlated with cytokine storms and TEX in lung squamous cell carcinoma. Conclusions: Cytokine storms may promote TEX through cytokine-receptor axes and be associated with poor prognosis in COVID-19. Blocking cytokine-receptor axes may reverse TEX. Our finding provides novel insights into TEX in COVID-19 and new clues for cytokine-targeted immunotherapy development.

Knowledge Mapping of the Links Between the Gut Microbiota and Heart Failure: A Scientometric Investigation (2006-2021).

Background: There is considerable research value and extensive application perspectives to explore the link between gut microbiota and heart failure. The purpose of this study is to provide an overview of overall characteristics, evolutionary pathways, frontier research hotspots, and future trends in this field. Methods: Research datasets were acquired from the Web of Science Core Collection (WoSCC) between January 1, 2006 and December 31, 2021. Three different analysis tools including one online platform, VOS viewer V1.6.17.0, and CiteSpace V5.8.R2 software were used in order to conduct collaboration network analysis, co-cited analysis, co-occurring analysis, and citation burst detection. Results: A total of 873 publications in the WoSCC database met the requirement. The overall characteristics analysis showed that a steady growth trend in the number of publications and citations, with the predominant literature type being articles and the most frequent subject category being cardiac cardiovascular systems. The United States was the most prolific country and the center of national collaboration. Cleveland Clinic and Nathalie M. Delzenne provided the leading influence with publications, the cooperation between the institutes and authors were relatively weak. Moreover, gut microbiota, heart failure, risk factor, obesity, and inflammation were the keywords that appeared more frequently in the clustering analysis of reference co-citation and keyword co-occurrence. Burst detection analysis of top keywords showed that trimethylamine N-oxide (TMAO), bile acid, blood pressure, hypertension, and fermentation were the new research foci on the association between gut microbiota and heart failure. Strategies to improve gut microbiota hold promise as a new approach to treat heart failure. Conclusion: The comprehensive bibliometric study indicates that the structured information may be helpful in understanding research trends in the link between gut microbiota and heart failure, and locating research hotspots and gaps in this domain, especially further advances in this field will lead to significant breakthroughs in the development of novel therapeutic tools for metabolic modulation of heart failure.