Identification of the potential association between SARS-CoV-2 infection and acute kidney injury based on the shared gene signatures and regulatory network.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is identified as the cause of coronavirus disease 2019 (COVID-19) pandemic. Acute kidney injury (AKI), one of serious complications of COVID-19 infection, is the leading contributor to renal failure, associating with high mortality of the patients. This study aimed to identify the shared gene signatures and construct the gene regulatory network between COVID-19 and AKI, contributing to exploring the potential pathogenesis. METHODS: Utilizing the machine learning approach, the candidate gene signatures were derived from the common differentially expressed genes (DEGs) obtained from COVID-19 and AKI. Subsequently, receiver operating characteristic (ROC), consensus clustering and functional enrichment analyses were performed. Finally, protein-protein interaction (PPI) network, transcription factor (TF)-gene interaction, gene-miRNA interaction, and TF-miRNA coregulatory network were systematically undertaken. RESULTS: We successfully identified the shared 6 candidate gene signatures (RRM2, EGF, TMEM252, RARRES1, COL6A3, CUBN) between COVID-19 and AKI. ROC analysis showed that the model constructed by 6 gene signatures had a high predictive efficacy in COVID-19 (AUC = 0.965) and AKI (AUC = 0.962) cohorts, which had the potential to be the shared diagnostic biomarkers for COVID-19 and AKI. Additionally, the comprehensive gene regulatory networks, including PPI, TF-gene interaction, gene-miRNA interaction, and TF-miRNA coregulatory networks were displayed utilizing NetworkAnalyst platform. CONCLUSIONS: This study successfully identified the shared gene signatures and constructed the comprehensive gene regulatory network between COVID-19 and AKI, which contributed to predicting patients' prognosis and providing new ideas for developing therapeutic targets for COVID-19 and AKI.

KAT2B is an immune infiltration-associated biomarker predicting prognosis and response to immunotherapy in non-small cell lung cancer.

BACKGROUND: Over the past few years, dramatic breakthroughs in the field of tumor immunotherapy with immune checkpoint inhibitors (ICIs) have made a therapeutic revolution for non-small cell lung cancer (NSCLC). While only some patients present a favorable response to this treatment. It is urgent to explore the potential molecular mechanisms underlying the regulation of tumor immune microenvironment in the process of immunotherapy. Lysine acetyltransferase 2B (KAT2B) plays a crucial role in the regulation of gene expression at the post-transcriptional level by acetylation, and is associated with many types of cancer. METHODS: RNA-sequencing data, genetic mutation data, and corresponding clinical information were extracted from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, then subjected to immune characteristics, gene expression, survival, genetic alteration, enrichment analyses. RESULTS: KAT2B expression correlated positively with infiltrating levels of multiple immune cells and mRNA expression levels of immune checkpoint genes in NSCLC. Furthermore, KAT2B expression was downregulated in tumor tissues, and low KAT2B expression was associated with unsatisfactory efficacy of immune checkpoint blockade (ICB) and poor prognosis of patients with lung adenocarcinoma. Moreover, there were higher somatic genes mutation frequency in patients with low expression of KAT2B. Finally, functional enrichment analysis suggested that KAT2B was mainly linked to the regulation of immune cells and interferon - gamma (IFN-γ) mediated signaling pathways, response to IFN-γ, antigen processing and presentation. CONCLUSION: This is the first comprehensive study to disclose that KAT2B is correlated with immune infiltrates and may serve as a novel biomarker predicting prognosis and response to immunotherapy in NSCLC.

Percutaneous Mechanical Thrombectomy for Acute Superior Mesenteric Artery Embolism: Preliminary Experience in Five Cases.

BACKGROUND: This study was performed to summarize our experience in treating acute superior mesenteric artery embolism (SMAE) by percutaneous mechanical thrombectomy (PMT). METHODS: The clinical data of five patients with acute SMAE treated by PMT in our center from October 2015 to May 2018 were retrospectively analyzed. PMT was performed under local anesthesia. Access was established via the femoral artery or brachial artery. Thrombectomy was performed on the superior mesenteric artery using a 6F Rotarex catheter (Straub Medical, Wangs, Switzerland). RESULTS: Technical success of PMT was achieved in all five patients; emboli were completely removed in three patients and partially removed in two patients. No PMT-related complications were noted after surgery. Four patients were smoothly discharged from the hospital after their symptoms were relieved. One patient still had symptoms of intestinal ischemia after the operation, and massive small intestinal necrosis was found by exploratory laparotomy. Intestinal resection was performed, and the patient died 4 months later. CONCLUSIONS: PMT by the Rotarex system is a minimally invasive, safe, and effective technique in removing SMAE. Early application of PMT can avoid intestinal necrosis.

Nasal epithelial barrier disruption by particulate matter ≤2.5 µm via tight junction protein degradation.

Upper airway diseases including sinonasal disorders may be caused by exposure to fine particulate matter (≤2.5 µm; PM2.5), as proven by epidemiological studies. PM2.5 is a complex entity whose chemical constituents and physicochemical properties are not confined to a single, independent "particle" but which in this study means a distinctive environmental "toxin." The mechanism whereby PM2.5 induces nasal epithelial barrier dysfunction leading to sinonasal pathology remains unknown. In the present study, human nasal epithelial cells were exposed to non-cytotoxic doses of PM2.5 to examine how PM2.5 affects the nasal epithelial barrier. Tight junction (TJ) integrity and function were assessed by transepithelial electric resistance and paracellular permeability. The expression levels of TJ proteins such as zona occludens-1, occludin and claudin-1 were assessed by immunofluorescence staining and western blot. PM2.5 exposure induced epithelial barrier dysfunction as reflected by increased paracellular permeability and decreased transepithelial electric resistance. TJ proteins zona occludens-1, occludin and claudin-1 were found to be downregulated. Pretreatment with N-acetyl-l-cysteine alleviated PM2.5-mediated reactive oxygen species generation in RPMI 2650 cells, further preventing barrier dysfunction and attenuating the degradation of TJ proteins. These results suggest that PM2.5 induces nasal epithelial barrier disruption via oxidative stress, and N-acetyl-l-cysteine counteracts this PM2.5-mediated effect. Thus, nasal epithelial barrier disruption caused by PM2.5, which leads to sinonasal disease, may be prevented or treated through the inhibition of reactive oxygen species.

[Clinicoradiologic characteristics of active pulmonary tuberculosis with perilymphatic involvement].

OBJECTIVE: To evaluate the prevalence of perilymphatic involvement and clinicoradiologic characteristics of active pulmonary tuberculosis according to the distribution of micronodules on CT images. METHODS: A total of 124 in-patients with active pulmonary tuberculosis in Haihe Clinical College of Tianjin Medical University from September 2013 to March 2015 were enrolled in this study, all patients underwent CT before antituberculosis therapy.A retrospective investigation of CT images focused on the distribution of micronodules, as well as other major CT features of active pulmonary tuberculosis.Clinical and CT findings of the three groups which based on the distribution of micronodules (perilymphatic, centrilobular and mixed) were compared. RESULTS: All patients existed micronodules.Among these patients, the number of the perilymphatic micronodules, interlobular septal thickening, intralobular septal thickening, bronchial or bronchovascular bundle thickening, galaxy or cluster sign, reversed halo sign was 80(64.5%), 83(66.9%), 56(45.2%), 56(45.2%), 17(13.7%) and 4(3.2%), respectively.There were 35, 36 and 45 cases who were classified into the perilymphatic, centrilobular and mixed groups, respectively.Interlobular septal thickening (88.6% vs 38.9%), intralobular septal thickening (97.1% vs 0), bronchial or bronchovascular bundle thickening (74.3% vs 19.4%) and galaxy or cluster sign (37.1% vs 0) in perilymphatic group were higher than those of centrilobular group, consolidation or macronodule (80% vs 100%) and cavitation (42.9% vs 77.8%) in perilymphatic group were lower than those of centrilobular group. Age (32±16 vs 41±14), the rate of sputum acid-fast bacilli smears staining positive (28.6% vs 58.3%) and sputum culture positive for Mycobacterium tuberculosis (54.3% vs 94.4%) in perilymphatic group were lower than those of centrilobular group. CONCLUSIONS: CT findings representing pulmonary perilymphatic involvement are relatively common in patients with active tuberculosis, galaxy or cluster sign and reversed halo sign are uncommon. The patients with tuberculosis are relatively younger who principally showed pulmonary perilymphatic involvement, and detection of sputum Mycobacterium tuberculosis in these patients is relatively lower.

Altered MicroRNA Expression Profiles in Activated Mast Cells Following IgE-FcεRI Cross-Linking with Antigen.

BACKGROUND/AIMS: MicroRNAs (miRNAs) are critical regulators of immune responses and immunologic disorders. However, little is known about miRNA expression and function during mast cell differentiation, proliferation and activation. This study aimed to determine the miRNA expression profiles in mast cells stimulated by immunoglobulin E (IgE) and antigen and to analyze the potential functions of specific miRNAs. METHODS: Bone marrow-derived mast cells (BMMCs) generated from differentiated mouse bone marrow cells were untreated (Unstimu) or stimulated with IgE-antigen complexes for 1 h or 6 h (Stimu). The miRNA profiles were evaluated by miRNA microarray. MiRNA target gene prediction and enrichment analyses were performed using bioinformatics. RESULTS: Seven significantly up-regulated and 10 down-regulated miRNAs were identified in the 1 h Stimu group relative to the Unstimu group (fold change>2; P<0.05). Of 8 miRNAs randomly selected from the 17 identified, the expression levels of 6 were confirmed by quantitative real-time PCR (qRT-PCR). The potential target genes of several candidate miRNAs were enriched in FcεRI signaling, response to stimulus and cellular exocytosis. CONCLUSION: The expression of many miRNAs changes following IgE-FcεRI cross-linking in activated mast cells, and these miRNAs probably play key regulatory roles in core signaling pathways and biological behaviors. Evaluating the functions of these characteristic miRNAs will further our understanding of IgE-associated allergic disease pathogenesis and the development of therapeutic strategies.

[Semi-quantitative study of structural abnormalities and changes of oxygenation function using CT in patients with post primary tuberculosis].

OBJECTIVE: To investigate the relationship between structural abnormalities with semi-quantitative score of CT and changes of oxygenation function in patients with post primary tuberculosis. METHODS: 110 in-patients with post primary tuberculosis in Haihe clinical college of Tianjin medical university from January 2014 to August 2014 were enrolled in this study, all patients underwent CT and blood gas analysis. All lesions in lung as a whole and different CT signs of lesions were evaluated by retrospective semi-quantitative score respectively, total scores obtained by adding the scores of different lesions. The correlation between these scores and the results of blood gas analysis were evaluated. CT scores were compared between group 1 (PaO2/FiO2<300 mmHg) and group 2 (PaO2/FiO2≥300 mmHg) of patients. RESULTS: Overall score of lung lesions and total scores which obtained by adding the score of different signs in patients showed correlation with PaO2/FiO2, and the method of overall score of lung lesions was easy to do. Scores of nodules and tree-in-bud pattern, consolidation, bronchial lesions, cavity showed correlation between PaO2/FiO2. There was no correlation between score of ground-glass opacity and PaO2/FiO2. Nodules and tree-in-bud pattern were more common in post primary tuberculosis, 87.3% (96/110) and 70% (77/110) respectively. Lobular consolidation was dominant in consolidation of patients, 83.6% (92/110). Bronchial wall thickening and bronchiectasis had higher incidence in larger airways, 87.3% (96/110) and 75.5% (83/110) respectively. Cavities were given priority to with thin walled, 53.6% (59/110). Overall score of lung lesions and scores of bronchial lesions, consolidation, cavity in groups 1 were significantly higher than group 2. CONCLUSIONS: Semi-quantitative score of CT can better quantify structural abnormalities of the lung, sensitively reflect changes of oxygenation, and bronchial lesions play an important role in the process of post primary tuberculosis.

[The lung function status in patients with severe acute respiratory syndrome after ten years of convalescence in Tianjin].

OBJECTIVE: To evaluate the lung function in patients with severe acute respiratory syndrome (SARS) 10 years after recovery and the influencing factors. METHODS: Pulmonary function tests were performed in 25 convalescent patients who had a diagnosis of SARS in 2003. Total lung volume, residual capacity, vital capacity, forced vital capacity (FVC), FEV1, FEV1/FVC and lung carbon monoxide diffusion (DLCO) were measured, and compared with the values obtained immediately after recovery in 2003. Of the 25 cases, 3 were males and 22 were females, aging 31-69 years [average (45.8 ± 12.2)]. Twenty-five healthy adults (6 males, 19 females), aged 31-62 years [average (42.3 ± 11.9) years], were recruited as controls. RESULTS: Of the 25 cases, 2 showed simple diffusion dysfunction, 2 simple restrictive ventilatory dysfunction, 11 combined diffusion and restrictive ventilatory dysfunction, and 1 combined diffusion and obstructive ventilatory dysfunction. The remaining 10 cases showed normal lung function. There were no statistical differences in the pulmonary function measurements as compared with those measured 10 years ago, including DLCO (73 ± 12)% vs (72 ± 15)% (P>0.05), FEV1/FVC (83 ± 11)% vs (85 ± 7)%, (P>0.05), FEV1 (88 ± 7)% vs (86 ± 14)% (P>0.05), FVC (87 ± 21)% vs (87 ± 17)% (P>0.05), and RV (100 ± 17)% vs (78 ± 3 0)% (P>0.05). The lung functions of the patients showed no significant difference as compared with those obtained from the healthy controls. CONCLUSIONS: The pulmonary functions of SARS patents largely returned to normal after 10 years of convalescence, and the lung function damage was characterized by diffusing and restrictive ventilatory dysfunctions.

[The effect of low molecular heparin and urokinase on MCP-1 of acute experimental pulmonary embolism in rabbits].

OBJECTIVE: To evaluate effect the of thrombolytic (urokinase, UK) and anticoagulant agent (low-molecular-weight heparin, LMWH) on the pulmonary injury of rabbits with acute pulmonary embolism (PE) by assaying monocyte chemoattractant protein-1 (MCP-1). METHODS: Rabbit models with PE were established by transfusing autologous blood clots on 60 healthy male Japanese white rabbits. Experimental PE rabbits were randomly divided into 3 groups:normal saline (NS) group (n = 18) , LMWH group (n = 18) and UK group (n = 18), and other 18 rabbits underwent sham operations as SHAM group (n = 18). Each group was divided into 3 subgroups based on 2 days (day 2), 4 days (day 4), and 14 days (day 14) after therapies. Arterial blood gas analysis was measured. MCP-1 levels in lung tissue and blood were assayed with ELISA at various times (day 2, day 4 and day 14 ). Fixed sections were stained with trichrome for intimal hyperplasia determination. RESULTS: The overall rate of success for making PE rabbit models was 90% (54/60), which was not affected by treatment. Compared with NS group, P(A-a)O2 significantly decreased in UK group. Compared with NS group, MCP-1 levels in lung tissue significantly decreased in LMWH group on day 4 [(33 ± 9) ng/L vs (48 ± 5) ng/L, P < 0.05] and day 14 [(30 ± 11) ng/L vs (41 ± 4) ng/L, P < 0.05]; MCP-1 levels in serum on day 14 also significantly decreased in LMWH group [(36 ± 10) ng/L vs (51 ± 5) ng/L, P < 0.05]. Compared with NS group, MCP-1 levels in lung tissue significantly decreased in UK group on day 2 and 4 [Day 2: (34 ± 8) ng/L vs (50 ± 4) ng/L, P < 0.05; Day 4: (29 ± 7) ng/L vs (48 ± 5) ng/L, P < 0.05]; MCP-1 levels in serum on day 2 and day 4 also significantly decreased in UK group [Day 2: (44 ± 3) ng/L vs (48 ± 3) ng/L, P < 0.05; Day 4: (44 ± 4) ng/L vs (53 ± 1)ng/L, P < 0.05]. CONCLUSIONS: UK treatment may rapidly improve V/Q ratio and decrease MCP-1 levels in lung tissue or serum, but it can not inhibit persistent inflammation. LMWH can decrease MCP-1 levels in lung tissue or serum, and inhibit persistent inflammation and late intimal hyperplasia.

Photodynamic Therapy of LD4-Photosensitizer Attenuates the Acute Pneumonia Induced by Klebsiella pneumoniae.

Klebsiella pneumoniae is a Gram-negative bacterium that induces acute lung injury (ALI) and inflammation in humans, necessitating immediate hospitalization and treatment. At present, the clinical treatment is largely dependent on hormones or antibiotics but is associated with drawbacks posed by the lack of eradication of the bacterium upon treatment and drug resistance. Therefore, there is an urgent need for novel and effective treatments. The current study investigated the treatment of K. pneumonia-induced ALI using a photosensitizer LD4 in conjunction with photodynamic therapy (PDT). The water content in the lungs (corresponding to edema) of a rat model of pneumonia induced by K. pneumoniae was reduced upon treatment with LD4-PDT. The counts of leukocyte, lymphocyte, and polymorphonuclear leukocyte in the blood were determined in the rat model of pneumonia, as were the concentrations of inflammatory cytokines (estimated using an enzyme-linked immunosorbent assay). The LD4-PDT treatment prominently reduced the levels of interleukin (IL)-6, IL-10, tumor necrosis factor-α, superoxide dismutase, and immune cells. Results suggest that LD4-PDT considerably alleviates the inflammation and oxidative stress caused by K. pneumoniae in the rat model of pneumonia. Furthermore, it could effectively improve the survival rate in the rat model of K. pneumonia-induced pneumonia and ameliorate histological changes while protecting the integrity of the pulmonary epithelial cells. These results highlight the potential application of LD4 as a photosensitizer for treating acute pneumonia induced by K. pneumoniae.

[High-fat diet induces pulmonary fibrosis in rats and inhibitory effects of N-acetylcysteine].

OBJECTIVE: To explore the relation between high-fat diet and pulmonary fibrosis and the inhibition of N-acetylcysteine (NAC) on lung tissue in rats. METHODS: Thirty Sprague Dawley (SD) male rats were randomly divided into control group (n = 10) on a quantitative control Lieber-DeCarli liquid diet, a high-fat diet group (n = 10) on a high fat-diet Lieber-DeCarli liquid diet and NAC group (n = 10) on NAC 300 mg×kg(-1)×d(-1). All rats were sacrificed 8 weeks later. The morphological changes and collagen deposition in lung tissue were observed by hematoxylin & eosin and Masson staining while the contents of glutathione (GSH) and hyaluronic acid (HA) measured through colorimetry and enzyme-linked immunosorbent assay. And the expression of transforming growth factor-ß1 (TGF-ß1) expression in lung tissue was detected through immunohistochemistry. RESULTS: There were variable degree of alveolar and alveolar septal infiltration of inflammatory cells. And more deposition of collagen fibers appeared at intervals of alveolar in high fat group. Similar pathological changes were found in NAC group, but the degree was lower than that of high-fat group. Compared to the control and NAC groups, the lung tissue content of GSH decreased (GSH: 0.11 ± 0.05 vs 0.19 ± 0.11, 0.22 ± 0.14 mg/g, both P < 0.05) while HA and TGF-ß1 increased in high-fat diet group (HA: 0.57 ± 0.06 vs 0.46 ± 0.04, 0.41 ± 0.04 mg/g; TGF-ß1: 24.6 ± 3.4 vs 16.8 ± 2.6, 11.7 ± 1.5, all P < 0.05). CONCLUSION: High-fat diet may induce pulmonary fibrosis in rats and NAC has inhibitory effects.

The Influence of Presentation Frames of Visualization Information for Safety on Situational Awareness under a Three-Level User-Interface Design.

To explore the influence of the construction and presentation frames of visualization information for safety (VIS) on people's situation awareness (SA), we designed a three-level user interface (UI) of VIS based on the three-stage SA theory, including perception (SA1), comprehension (SA2), and projection (SA3). Then, 166 subjects were recruited and divided into three groups to participate in the experiment, in which SA was measured by the situation-present-assessment method (SPAM) and situation-awareness-rating technique (SART), and eye-movement data were recorded. The results show that the level-3 UI design could effectively improve the subjects' SA levels. Although the increase in VIS displayed caused by the higher UI level led to a decrease in the perception-stage score of SA, the level-3 UI fully considered the three stages of human information processing, and helped improve the SA of the subjects; the overall SA score measured using the SART method was not significant, but the result was consistent with the SPAM. There was a framing effect on the presentation of VIS, and subjects perceived different degrees of risk under different presentation frames; that is, less risk under the positive frame, more risk under the negative frame, and a higher level of SA under the positive frame compared with the negative frame. To some extent, the nearest-neighbor-index (NNI) algorithm could be utilized to quantify subjects' eye-tracking fixation mode. While the frames were guided by the high-level interface and the positive presentation frame, the distribution of the subjects' gaze points was more discrete; they could grasp the relevant information more comprehensively and had a relatively high level of SA. To some extent, this study can provide a reference for the design and optimization of the VIS presentation interface.

Early lexical processing of Chinese one-character words and Mongolian words: A comparative study using event-related potentials.

Logographic language and alphabetic language differ significantly in orthography. Investigating the commonality and particularity of visual word recognition between the two distinct writing systems is informative for understating the neural mechanisms underlying visual word recognition. In the present study, we compared the chronometry of early lexical processing and the brain regions involved in early lexical processing between Chinese (logographic language) and Mongolian (alphabetic language) by recording event-related potentials (ERPs) using both implicit and explicit reading tasks. Familiar Chinese one-character words (lexical) and unknown Chinese one-character words (non-lexical) were pseudorandomly presented to native Chinese readers in Experiment 1. Mongolian words (lexical) and pseudowords (non-lexical) were pseudorandomly presented to native Mongolian readers in Experiment 2. In the color decision task, participants were asked to decide the color (black or blue) of each stimulus. In the lexical recognition task, participants were asked to report whether they could recognize each stimulus. The results showed that in both experiments and both tasks, ERPs to lexical items differed significantly from those to non-lexical items in the parietooccipital scalp region approximately 250 ms after stimulus onset, reflecting the early lexical processing, which likely originated from the ventral occipitotemporal cortex as revealed by source analysis. These results indicated that although Chinese and Mongolian differed markedly in orthographic features, the neural mechanisms underlying early lexical processing are similar between the two languages.

[Clinical study of awake prone positioning treatment in patients with common coronavirus disease 2019 caused by Omicron variant].

OBJECTIVE: To evaluate the clinical effect of awake prone positioning (APP) for common coronavirus disease 2019 (COVID-19) caused by Omicron variant. METHODS: Retrospectively analyze the clinical data of patients with COVID-19 caused by Omicron variant admitted by medical team of Tianjin Third Central Hospital during the period of supporting Tianjin COVID-19 designated hospital from January 8 to February 20, 2022. Patients who met the diagnostic criteria for common COVID-19 and had risk factors for developing severe disease or had pulse oxygen saturation (SpO2) ≤ 0.93 after exercise without supplementary oxygen were enrolled. Patients were divided into APP group and control group according to whether they completed the daily 12-hours APP in the first three days after enrollment. Demographic characteristics, clinical symptoms, COVID-19 vaccination status, laboratory examination, disease progression (progression to severe), time to nucleic acid negative conversion, length of hospital stay, and adverse reactions and tolerability [visual analog scale (VAS) score (the higher the score, the worse the tolerability] during APP were evaluated in two groups. Interleukin-6 (IL-6), C-reactive protein (CRP), SpO2/inhaled oxygen concentration (FiO2) ratio and ROX index (ROXI) were compared between two groups at enrollment, 3rd and 7th day after enrollment. RESULTS: There were no significant differences in demographic characteristics, clinical symptoms, vaccination rates of COVID-19 and laboratory tests between the two groups. There were no statistically significant differences in IL-6, CRP, SpO2/FiO2 ratio and ROXI between two groups at the time of enrollment. Compared with the group at the time of enrollment, SpO2/FiO2 ratio and ROXI in APP group increased significantly at the 3rd day after enrollment [SpO2/FiO2 ratio: 461.90 (457.10, 466.70) vs. 446.67 (437.14, 457.10), ROXI: 25.40 (23.33, 25.93) vs. 22.57 (21.86, 24.40), all P < 0.05], and the levels of IL-6 and CRP in control group were significantly increased [IL-6 (ng/L): 18.30 (6.50, 37.75) vs. 7.40 (5.10, 11.15), CRP (mg/L): 11.46 (2.11, 17.96) vs. 4.11 (1.72, 9.05), all P < 0.05]. At the 3rd day of enrollment, the levels of IL-6 and CRP in APP group were significantly lower than those in control group [IL-6 (ng/L): 7.35 (4.35, 12.80) vs. 18.30 (6.50, 37.75), CRP (mg/L): 4.52 (1.98, 9.66) vs. 11.46 (2.11, 17.96), all P < 0.05], while SpO2/FiO2 ratio and ROXI were significantly higher than those in control group [SpO2/FiO2 ratio: 461.90 (457.10, 466.70) vs. 446.67 (441.90, 459.52), ROXI: 25.40 (23.33, 25.93) vs. 23.31 (22.10, 24.66), all P < 0.05]. At the 7th day of enrollment,there were no significant differences in IL-6, CRP, SpO2/FiO2 ratio and ROXI between two groups. There were no severe cases in both groups. The time of nucleic acid negative conversion and length of hospital stay in APP group were significantly shorter than those in control group [10.0 (8.0, 12.0) days vs. 11.0 (9.0, 13.0) days, 12.0 (10.0, 14.0) days vs. 14.0 (12.0,16.0) days, respectively, all P < 0.05]. The main adverse reaction during APP was back pain, and the incidence in APP group was slightly lower than that in control group, but the difference was not statistically significant [17.9% (17/95) vs. 26.5% (27/102), P = 0.149]. VAS score in control group was significantly higher than that in APP group [score: 2.5 (2.0, 4.0) vs. 2.0 (1.0, 3.0), P = 0.004]. CONCLUSIONS: In common COVID-19 patients caused by Omicron variant with high risk factors for progression to severe disease or decreased oxygen reserve capacity, early APP can shorten the time of nucleic acid negative conversion and the length of hospital stay, but its effect on preventing disease progression cannot be determined.

[Analysis of clinical characteristics of 362 vaccinated or unvaccinated patients infected by novel coronavirus Omicron variant].

OBJECTIVE: To analyze the epidemiological and clinical characteristics of patients infected by novel coronavirus Omicron variant, and also to analyze whether vaccination against novel coronavirus has an impact on the severity and prognosis of Omicron patients. METHODS: A prospective, single-center observational study was conducted to collect data of consecutive patients with Omicron variant infection admitted to the designated hospital for coronavirus disease 2019 (COVID-19) charged by Tianjin COVID-19 rescue medical team of Tianjin Third Central Hospital, from January 8 to February 2, 2022. The clinical characteristics of the patients were analyzed, and the influence of whether the patients were inoculated with booster vaccination on the condition and outcome was analyzed. Data were collected including epidemiological, clinical features, laboratory and imaging examination, treatment measures and clinical outcomes, and difference between groups was analyzed. RESULTS: A total of 362 patients were included, including 136 cases (37.57%) in the booster group, 190 cases (52.49%) in the routine vaccination group, and 36 cases (9.94%) in the unvaccinated group. There was a trend of concentrated distribution of patients, of which 171 cases (47.24%) patients showed family clustering, involving 69 families. Seventy-four cases (20.44%) of the 362 patients had one or more underlying diseases, mainly hypertension (64 cases, 17.68%), diabetes mellitus (23 cases, 6.35%), and coronary heart disease (18 cases, 4.97%); 215 patients (59.39%) had one or more discomfort symptoms, mainly cough (158 cases, 43.65%), pharyngeal discomfort (154 cases, 42.54%) and fever (136 cases, 37.57%). The diagnostic typing was mild type in 194 cases (53.59%), moderate type in 165 cases (45.58%) and severe type in 3 cases (0.83%). The patients had elevated immunoglobulin G (IgG) antibody titers to the novel coronavirus on admission [23.17 (3.08, 60.77)]. Patients were medically isolated and the main treatment measures included traditional Chinese medicine identification (Chinese medicine or tonics) in 265 cases (73.20%), prone treatment in 188 cases (51.93%), anticoagulation with low-molecular heparin in 106 cases (29.28%), immunomodulatory therapy with thymofacine in 21 cases (5.80%), antimicrobial drugs in 20 cases (5.52%), transnasal high-flow oxygen therapy in 12 cases (3.31%), glucocorticoids in 5 cases (1.38%), non-invasive mechanical ventilation in 1 case (0.28%), and invasive mechanical ventilation in 1 case (0.28%). A total of 362 patients were discharged with no deaths, of which 12 patients (3.31%) were admitted to the intensive care unit (ICU). The median duration of illness was 13 (10, 15) days, the median length of hospitalization was 13 (11, 15) days, and the median time to nucleic acid conversion was 13 (10, 15) days. Compared with the unvaccinated group, the IgG antibody titers of patients in the booster and routine vaccination groups [41.49 (20.32, 81.38), 19.94 (2.33, 49.25) vs. 0.16 (0.07, 1.94)] and the proportion of mild patients [66.91% (91/136), 48.94% (93/190) vs. 27.28% (10/36)] were higher, which were also higher in the booster vaccination group than in the conventional vaccination group (all P < 0.05). Compared to the conventional and booster vaccination groups, the unvaccinated group had a higher proportion of severe patients [5.56% (2/36) vs. 0.53% (1/190), 0 (1/136)], longer time to nucleic acid conversion [days: 15 (11, 16) vs.12 (10, 15), 13 (11, 15)], and longer disease duration [days: 15 (11, 16) vs. 12 (10, 15), 13 (11, 15)], and a higher percentage of ICU admissions [16.67% (6/36) vs. 2.63% (5/190), 0.74% (1/136)], with statistically significant differences among the three groups (all P < 0.05). CONCLUSIONS: Omicron variant is extremely infectious with aggregated onset, but its clinical symptoms are mild. The vaccine, especially the booster vaccination, remains effective in preventing severe-stage progression and improving prognosis in patients with Omicron variant infection.

ß-Carboline dimers inhibit the tumor proliferation by the cell cycle arrest of sarcoma through intercalating to Cyclin-A2.

ß-Carbolines are potentially strong alkaloids with a wide range of bioactivities, and their dimers exhibit stronger antitumor activity other than the monomers. However, the detailed mechanisms of the ß-carboline dimers in inhibiting sarcoma (SARC) remain unclear. The results showed that ß-carboline-3-carboxylic acid dimers Comp1 and Comp2, which were synthesized in our lab and modified at the N9 position and linked at the C3 position, exhibited effective inhibition activity on MG-63 proliferation (IC50 = 4.6µM). Meanwhile, the large scale transcriptome profiles of SARC from The Cancer Genome Atlas (TCGA) were analyzed, and found that abnormal expression of genes relevant to apoptosis, cell cycle, and signaling pathways of Hedgehog, HIF, Ras involved in the SARC pathogenesis. Interestingly, both dimers could promote the apoptosis and arrest the cell cycle in S phase to inhibit proliferation of MG-63. Moreover, Comp1 and Comp2 inhibited the expression CDK2, CCNA2, DBF4, and PLK1 associated with various immune cells and cell cycle in MG-63. Remarkably, drug-target interaction network analysis showed that numerous proteins involved in cell cycle were the potential targets of Comp1 and Comp2, especially CCNA2. Further molecular docking, isothermal titration calorimetry (ITC) and Cellular Thermal Shift Assay (CETSA) confirmed that both dimers could directly interact with CCNA2, which is significantly correlated with CD4+ T cells, by strong hydrophobic interactions (Kd=5.821 ×106 N). Meanwhile, the levels of CCNA2 and CDK2 were inhibited to decrease in MG-63 by both dimer treatments at transcription and protein levels, implying that Comp1 and Comp2 blocked the interaction between CCNA2 and CDK2 through competitive binding with CCNA2 to arrest the cell cycle of MG-63 cells in the S phase. Additionally, the transcriptome profiles of ß-carboline-treated mice from Gene Expression Omnibus (GEO) were obtained, and found that similar antitumor mechanism was shared among ß-carboline derivatives. Overall, our results elucidated the antitumor mechanisms of Comp1 and Comp2 through dual-suppressing the function of CCNA2 to profoundly arrest cell cycle of MG-63, then effectively inhibited cell proliferation of MG-63. These results provide new insights into the antitumor mechanism of ß-carboline dimers and new routes of various novel cancer-related drug targets for future possible cancer therapy.

Glutamine Metabolism Is Required for Alveolar Regeneration during Lung Injury.

(1) Background: Abnormal repair after alveolar epithelial injury drives the progression of idiopathic pulmonary fibrosis (IPF). The maintenance of epithelial integrity is based on the self-renewal and differentiation of alveolar type 2 (AT2) cells, which require sufficient energy. However, the role of glutamine metabolism in the maintenance of the alveolar epithelium remains unclear. In this study, we investigated the role of glutamine metabolism in AT2 cells of patients with IPF and in mice with bleomycin-induced fibrosis. (2) Methods: Single-cell RNA sequencing (scRNA-seq), transcriptome, and metabolomics analyses were conducted to investigate the changes in the glutamine metabolic pathway during pulmonary fibrosis. Metabolic inhibitors were used to stimulate AT2 cells to block glutamine metabolism. Regeneration of AT2 cells was detected using bleomycin-induced mouse lung fibrosis and organoid models. (3) Results: Single-cell analysis showed that the expression levels of catalytic enzymes responsible for glutamine catabolism were downregulated (p < 0.001) in AT2 cells of patients with IPF, suggesting the accumulation of unusable glutamine. Combined analysis of the transcriptome (p < 0.05) and metabolome (p < 0.001) revealed similar changes in glutamine metabolism in bleomycin-induced pulmonary fibrosis in mice. Mechanistically, inhibition of the key enzymes involved in glucose metabolism, glutaminase-1 (GLS1) and glutamic-pyruvate transaminase-2 (GPT2) leads to reduced proliferation (p < 0.01) and differentiation (p < 0.01) of AT2 cells. (4) Conclusions: Glutamine metabolism is required for alveolar epithelial regeneration during lung injury.

Transumbilical single-incision laparoscopic resection of ileocecal junction for benign disease: first report of two cases.

BACKGROUND: Transumbilical single-incision laparoscopic surgery (TUSILS) has emerged as an advanced technique for minimally invasive surgery. Recently, the authors performed TUSIL resection of the ileocecal junction for benign lesions. METHODS: The authors report the surgical technique and clinical effect of TUSIL resection of the ileocecal junction in 2 patients. RESULTS: The 2 operations were completely successful with satisfactory and scarless recovery. No postoperative complications occurred. CONCLUSIONS: TUSIL resection of the ileocecal junction was feasible and safe in the 2 patients and might lead to an expansion of the indications for TUSILS.

Application of loop-mediated isothermal amplification and next-generation sequencing in the diagnosis of maternal tuberculosis with multiple negative tests: A case report.

RATIONALE: Tuberculosis (TB) is one of the top 10 causes of death worldwide and is the leading infectious cause of death. The incidence of TB, especially active TB, is increased in pregnant and postpartum women. Newborns can be infected with TB from their mothers through several routes. Diagnosis of TB in pregnant women and infants is difficult. Here, we report the simultaneous postdelivery diagnosis of TB in a mother and infant pair. PATIENT CONCERNS: A 28-year-old woman presented with a sudden onset of convulsions, loss of consciousness, coughing, fever, and breathing difficulty. Her 18-day-old infant daughter developed cough and wheezing. DIAGNOSIS: The mother's chest computed tomography showed diffuse interstitial changes and both lungs' exudation. Enhanced cranial magnetic resonance imaging showed scattered nodular intracranial lesions. A tuberculin skin test and an interferon-gamma release assay were negative. Xpert MTB/RIF (Xpert) testing and acid-fast bacilli smear of bronchoalveolar lavage (BAL) fluid of the mother were negative. Loop-mediated isothermal amplification of BAL fluid was positive for Mycobacterium tuberculosis, and next-generation sequencing confirmed the diagnosis of TB. A biopsy specimen also showed characteristic TB findings. The mother was diagnosed with TB and TB encephalitis. The infant's BAL fluid was positive for acid-fast bacilli and Xpert and, therefore, was diagnosed with TB. INTERVENTIONS: The mother was treated with rifampicin and isoniazid for 9 months, ethambutol and pyrazinamide for 3 months, and prednisolone acetate for 8 weeks. The infant received ventilator-assisted ventilation for 10 days and anti-tuberculous therapy for 11 months. OUTCOMES: After anti-tuberculous therapy, the mother and infant both gradually recovered. The mother's chest computed tomography showed significant recovery 9 months after discharge. The infant developed normally during the 11-month follow-up. LESSONS: This mother-child case pair highlights the value of loop-mediated isothermal amplification and next-generation sequencing as new diagnostic technologies for diagnosing TB in patients with multiple negative tests.

Percutaneous Mechanical Atherectomy Plus Thrombectomy Using the Rotarex®S Device Followed by a Drug-Coated Balloon for the Treatment of Femoropopliteal Artery In-stent Restenosis: A Prospective Single-Center, Single-Arm Efficacy Trial (PERMIT-ISR Trial).

Background: Studies investigating debulking devices with drug-coated balloons (DCBs) in the treatment of femoropopliteal (FP) artery in-stent restenosis (ISR) are limited. We aimed to evaluate the safety and midterm outcome of percutaneous mechanical atherectomy plus thrombectomy (MATH) using the Rotarex®S (Straub Medical, Wangs, Switzerland) catheter followed by a DCB in the treatment of FP-ISR. Methods: This study was a single-center single-arm trial. Patients with symptomatic (Rutherford category 2-5) de novo restenosis lesions of FP-ISR were treated with MATH and subsequent DCB. From June 2016 to May 2018, 59 patients with FP-ISR were enrolled. The primary endpoint was target lesion revascularization (TLR) and changes in the Rutherford category of the target limb at 12 months. Secondary endpoints included primary and secondary patency at 12 months, technical success rate, major adverse events, and ankle-brachial index (ABI). Risk factors for TLR were analyzed using Cox proportional hazard model. Results: The average follow-up time was 33 ± 8 months. The rate of technical success was 88.1% (52/59). Nine patients received bailout stenting. The rate of freedom from TLR was 84.7% (50/59) at 1 year, the Rutherford category changed at 12 months were significantly improved from baseline (p < 0.01). The primary patency rates and the secondary patency at the 12-month follow-ups were 82.5 and 92.5%, respectively. The ABI changed at 12 months were significantly improved from baseline (p < 0.01). Global limb anatomic staging system (GLASS) classification III [hazard ratio (HR) 18.44, 95% CI (1.57-215.99), p = 0.020] and postoperative Rutherford classification ≥4 [HR 8.28, 95% CI (1.85-37.06), p = 0.006] were identified as independent predictors of TLR. Conclusion: Our preliminary data suggested that MATH using a Rotarex®S catheter combined with DCB angioplasty is a safe, minimally invasive, and effective treatment for FP-ISR with favorable, immediate, and midterm outcomes. Clinical Trial Registration:http://www.chictr.org.cn, identifier [ChiCTR2000041380].