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.

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.

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.

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.

[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.

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.

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.

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.

Targeting Oncogenic miR-181a-2-3p Inhibits Growth and Suppresses Cisplatin Resistance of Gastric Cancer.

PURPOSE: This study aimed to explore the value of miR-181a-2-3p in cisplatin (DDP) treatment effectiveness prediction, and to reveal the function underlying the reversal of DDP resistance in patients with gastric cancer (GC). METHODS: miRNA expression dataset of three DDP-resistant GC cell lines and their DDP-sensitive parental cell lines obtained from GEO DataSets and GenBank, and functional miRNAs were annotated by bioinformatics analyses. Serum specimens and tumor samples were collected from 91 GC patients for understanding of the interrelation between chemotherapy response and miRNA expression. RT-qPCR validated these miRNAs at the transcriptional level in both gastric cancer cells and 91 gastric cancer patients. The correlation between the miRNAs expression and clinical parameters of the patients were analyzed. Receiver operating characteristics (ROC) analysis has been utilized to assess the diagnostic performance. The MTT and colony formation assays were performed to assess cell proliferation. Flow cytometry was conducted to detect cell apoptosis. DDP-resistant GC cells and their DDP-sensitive parental cells were transfected with miRNA mimic or inhibitor vector to overexpress or downregulate miRNA expression. RESULTS: miR-181a-2-3p as a unique miRNA was found in the common differentially expressed-miRNAs (DE-miRNAs) after miRNA screening and validation from three DDP-resistant and DDP-sensitive gastric cancer cell lines. Clinical data analysis displayed that miR-181a-2-3p expression was apparently increased in larger tumor size (≥5 cm), higher T stage (T4), and chemotherapy resistance. miR-181a-2-3p (AUC=0.926, SE=0.028, 95% CI: 0.872-0.980, p< 0.0001) differentiated chemosensitive GC patients from chemoresistant GC patients. miR-181a-2-3p presented a higher level in gastric cancer, and could serve as a valid biomarker to predict the overall survival of GC patients. Upregulation of miR-181a-2-3p rendered the apoptosis-inducing and anti-proliferative effects of DDP, while downregulating it decreased these effects. CONCLUSION: miR-181a-2-3p can function as a therapeutic target and a tumor biomarker. Targeting oncogenic miR-181a-2-3p inhibits growth and suppresses cisplatin resistance of gastric cancer.

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].

Endovascular treatment of aortic saddle embolism through percutaneous mechanical Thrombectomy via Straub Rotarex catheter.

BACKGROUND: To summarize our experience of endovascular treatment for abdominal aorta saddle embolism (ASE) through percutaneous mechanical thrombectomy (PMT). METHODS: Clinical data of three ASE patients treated with an endovascular approach using percutaneous mechanical thrombectomy (PMT) were reviewed and analyzed. RESULTS: After PMT, blood flow of limbs was restored in all of the three patients. However, two patients died from sudden cardiac arrest caused by hyperkalemia several hours after the procedure. The other one patient survived through continuous renal replacement therapy, which was initialized shortly after the surgical procedure. CONCLUSION: Endovascular treatment through PMT can quickly restore blood flow in the ASE patients. Blood purification through renal replacement therapy is crucial to reduce mortality after restoring blood flow of the limbs.

Endovascular therapy for floating thrombus in the inferior vena cava.

OBJECTIVE: We aimed to summarize the clinical characteristics of floating thrombus in the inferior vena cava (IVC). METHODS: From January 2014 to June 2019, four patients with floating thrombus in the IVC were admitted to our hospital and underwent intracavitary therapy. Diagnosis, therapy, and clinical characteristics of floating thrombus were summarized. RESULTS: Three patients presented with pulmonary embolism. Three of the patients had a floating thrombus discovered by inferior venacavography and one was found by contrast-enhanced computed tomography. Two patients had deep venous thrombosis in the lower extremities. One patient had a double IVC, one had left iliac vein compression syndrome, and one had right renal phlebothrombosis. The four patients underwent implantation of a temporary IVC filter and were treated with anti-coagulation, debulking, and thrombolysis. All four patients achieved satisfactory results. CONCLUSIONS: Floating thrombus in the IVC is often caused by spread of branch vein thrombosis, and is more likely to lead to pulmonary embolism. Anti-coagulant therapy and debulking under the protection of filters can achieve satisfactory clinical results.

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.

Airway epithelial regeneration requires autophagy and glucose metabolism.

Efficient repair of injured epithelium by airway progenitor cells could prevent acute inflammation from progressing into chronic phase in lung. Here, we used small molecules, genetic loss-of-function, organoid cultures, and in vivo lung-injury models to show that autophagy is essential for maintaining the pool of airway stem-like vClub cells by promoting their proliferation during ovalbumin-induced acute inflammation. Mechanistically, impaired autophagy disrupted glucose uptake in vClub progenitor cells, and either reduced accessibility to glucose or partial inhibition of glycolysis promoted the proliferative capacity of vClub progenitor cells and their daughter Club cells. However, glucose deprivation or glycolysis blockade abrogated the proliferative capacity of airway vClub cells and Club cells but promoted ciliated and goblet cell differentiation. Deficiency of glucose transporter-1 suppressed the proliferative capacity of airway progenitor cells after ovalbumin challenge. These findings suggested that autophagy and glucose metabolism are essential for the maintenance of airway epithelium at steady state and during allergic inflammation.

Safety and Efficacy of a Novel Shunt Surgery Combined with Foam Sclerotherapy of Varices for Prehepatic Portal Hypertension: A Pilot Study.

OBJECTIVES: This pilot study investigated the safety and efficacy of a novel shunt surgery combined with foam sclerotherapy of varices in patients with prehepatic portal hypertension. METHODS: Twenty-seven patients who were diagnosed with prehepatic portal hypertension and underwent shunt surgeries were divided into three groups by surgery type: shunt surgery alone (Group A), shunt surgery and devascularization (Group B), and shunt surgery combined with foam sclerotherapy (Group C). Between-group differences in operation time, intraoperative blood loss, portal pressure decrease, postoperative complications, rebleeding rates, encephalopathy, mortality rates and remission of gastroesophageal varices were compared. RESULTS: Groups A, B and C had similar operation times, intraoperative bleeding, and portal pressure decrease. The remission rates of varices differed significantly (p<0.001): one patient in Group A and 6 patients in Group B had partial response, and all 9 patients in Group C had remission (2 complete, 7 partial). Two Group A patients and one Group B patient developed recurrent gastrointestinal bleeding postoperatively within 12 months. No postoperative recurrence or bleeding was observed in Group C, and no sclerotherapy-related complications were observed. CONCLUSIONS: Shunt surgery combined with foam sclerotherapy obliterates varices more effectively than shunt surgery alone does, decreasing the risk of postoperative rebleeding from residual gastroesophageal varices. This novel surgery is safe and effective with good short-term outcomes.

Safety and efficacy of a novel shunt surgery combined with foam sclerotherapy of varices for prehepatic portal hypertension: a pilot study

OBJECTIVES: This pilot study investigated the safety and efficacy of a novel shunt surgery combined with foam sclerotherapy of varices in patients with prehepatic portal hypertension. METHODS: Twenty-seven patients who were diagnosed with prehepatic portal hypertension and underwent shunt surgeries were divided into three groups by surgery type: shunt surgery alone (Group A), shunt surgery and devascularization (Group B), and shunt surgery combined with foam sclerotherapy (Group C). Between-group differences in operation time, intraoperative blood loss, portal pressure decrease, postoperative complications, rebleeding rates, encephalopathy, mortality rates and remission of gastroesophageal varices were compared. RESULTS: Groups A, B and C had similar operation times, intraoperative bleeding, and portal pressure decrease. The remission rates of varices differed significantly (p<0.001): one patient in Group A and 6 patients in Group B had partial response, and all 9 patients in Group C had remission (2 complete, 7 partial). Two Group A patients and one Group B patient developed recurrent gastrointestinal bleeding postoperatively within 12 months. No postoperative recurrence or bleeding was observed in Group C, and no sclerotherapy-related complications were observed. CONCLUSIONS: Shunt surgery combined with foam sclerotherapy obliterates varices more effectively than shunt surgery alone does, decreasing the risk of postoperative rebleeding from residual gastroesophageal varices. This novel surgery is safe and effective with good short-term outcomes.