Uncovering the cellular and omics characteristics of natural killer cells in the bone marrow microenvironment of patients with acute myeloid leukemia.

BACKGROUND: Acute myeloid leukemia (AML) is a highly heterogeneous hematologic malignancy and the most frequently acute leukemia of stem cell precursors and the myeloid derivatives in adult. Longitudinal studies have indicated the therapeutic landscape and drug resistance for patients with AML are still intractable, which largely attribute to the deficiency of detailed information upon the pathogenesis. METHODS: In this study, we compared the cellular phenotype of resident NK cells (rAML-NKs, rHD-NKs) and expanded NK cells (eAML-NKs, eHD-NKs) from bone marrow of AML patients (AML) and healthy donors (HD). Then, we took advantage of the co-culture strategy for the evaluation of the in vitro cytotoxicity of NK cells upon diverse tumor cell lines (e.g., K562, Nalm6, U937). With the aid of RNA-sequencing (RNA-SEQ) and bioinformatics analyses (e.g., GOBP analysis, KEGG analysis, GSEA, volcano plot), we verified the similarities and differences of the omics features between eAML-NKs and eHD-NKs. RESULTS: Herein, we verified the sharp decline in the content of total resident NK cells (CD3-CD56+) in rAML-NKs compared to rHD-NKs. Differ from the expanded eHD-NKs, eAML-NKs revealed decline in diverse NK cell subsets (NKG2D+, CD25+, NKp44+, NKp46+) and alterations in cellular vitality but conservations in cytotoxicity. According to transcriptomic analysis, AML-NKs and HD-NKs showed multifaceted distinctions in gene expression profiling and genetic variations. CONCLUSIONS: Collectively, our data revealed the variations in the cytobiological and transcriptomic features between AML-NKs and HD-NKs in bone marrow environment. Our findings would benefit the further development of novel biomarkers for AML diagnosis and NK cell-based cytotherapy in future.

Metabolic score tool for personalized acute pancreatitis prognosis: A multicenter analysis.

Increasing evidence suggests that body composition is associated with the development of acute pancreatitis (AP). This study aimed to investigate the applicability of body composition in predicting AP severity. Data of 213 patients with AP from Affiliated Hospital of Putian University (AHOPTU) were included in this study, whilst data of 173 patients with AP from Fujian Medical University Union Hospital (FMUUH) were used for external validation. Patients were classified into the non-severe and severe groups according to AP severity. After seven days of treatment, in patients from AHOPTU, the difference in skeletal muscle index before and after treatment (ΔSMI) was significantly higher (P = 0.002), while the skeletal muscle radiodensity before treatment (PreSMR) was significantly lower (P = 0.042) in the non-severe group than in the severe group. The multivariate logistic regression model also revealed that the ΔSMI and PreSMR were independent risk factors for AP severity. The optimal cut-off values of ΔSMI and PreSMR were 1.0 and 43.7, respectively. The following metabolic score (SMS) was established to predict AP severity: 0: ΔSMI < 1.0 and PreSMR < 43.7; 1: ΔSMI ≥ 1.0 and PreSMR < 43.7 or ΔSMI < 1.0 and PreSMR ≥ 43.7; 3: ΔSMI ≥ 1.0 and PreSMR ≥ 43.7. In patients from AHOPTU and FMUUH, the areas under the curves (AUC) for this model were 0.764 and 0.741, respectively. ΔSMI and PreSMR can accurately predict AP severity. It is recommended to routinely evaluate the statuses of patients with AP using the predictive model presented in this study for individualized treatment.

The gut-lung axis in critical illness: microbiome composition as a predictor of mortality at day 28 in mechanically ventilated patients.

BACKGROUND: Microbial communities are of critical importance in the human host. The lung and gut microbial communities represent the most essential microbiota within the human body, collectively referred to as the gut-lung axis. However, the differentiation between these communities and their influence on clinical outcomes in critically ill patients remains uncertain. METHODS: An observational cohort study was obtained in the intensive care unit (ICU) of an affiliated university hospital. Sequential samples were procured from two distinct anatomical sites, namely the respiratory and intestinal tracts, at two precisely defined time intervals: within 48 h and on day 7 following intubation. Subsequently, these samples underwent a comprehensive analysis to characterize microbial communities using 16S ribosomal RNA (rRNA) gene sequencing and to quantify concentrations of fecal short-chain fatty acids (SCFAs). The primary predictors in this investigation included lung and gut microbial diversity, along with indicator species. The primary outcome of interest was the survival status at 28 days following mechanical ventilation. RESULTS: Sixty-two mechanically ventilated critically ill patients were included in this study. Compared to the survivors, the diversity of microorganisms was significantly lower in the deceased, with a significant contribution from the gut-originated fraction of lung microorganisms. Lower concentrations of fecal SCFAs were detected in the deceased. Multivariate Cox regression analysis revealed that not only lung microbial diversity but also the abundance of Enterococcaceae from the gut were correlated with day 28 mortality. CONCLUSION: Critically ill patients exhibited lung and gut microbial dysbiosis after mechanical ventilation, as evidenced by a significant decrease in lung microbial diversity and the proliferation of Enterococcaceae in the gut. Levels of fecal SCFAs in the deceased served as a marker of imbalance between commensal and pathogenic flora in the gut. These findings emphasize the clinical significance of microbial profiling in predicting the prognosis of ICU patients.

Acute pancreatitis: A review of diagnosis, severity prediction and prognosis assessment from imaging technology, scoring system and artificial intelligence.

Acute pancreatitis (AP) is a potentially life-threatening inflammatory disease of the pancreas, with clinical management determined by the severity of the disease. Diagnosis, severity prediction, and prognosis assessment of AP typically involve the use of imaging technologies, such as computed tomography, magnetic resonance imaging, and ultrasound, and scoring systems, including Ranson, Acute Physiology and Chronic Health Evaluation II, and Bedside Index for Severity in AP scores. Computed tomography is considered the gold standard imaging modality for AP due to its high sensitivity and specificity, while magnetic resonance imaging and ultrasound can provide additional information on biliary obstruction and vascular complications. Scoring systems utilize clinical and laboratory parameters to classify AP patients into mild, moderate, or severe categories, guiding treatment decisions, such as intensive care unit admission, early enteral feeding, and antibiotic use. Despite the central role of imaging technologies and scoring systems in AP management, these methods have limitations in terms of accuracy, reproducibility, practicality and economics. Recent advancements of artificial intelligence (AI) provide new opportunities to enhance their performance by analyzing vast amounts of clinical and imaging data. AI algorithms can analyze large amounts of clinical and imaging data, identify scoring system patterns, and predict the clinical course of disease. AI-based models have shown promising results in predicting the severity and mortality of AP, but further validation and standardization are required before widespread clinical application. In addition, understanding the correlation between these three technologies will aid in developing new methods that can accurately, sensitively, and specifically be used in the diagnosis, severity prediction, and prognosis assessment of AP through complementary advantages.

Decoding the biological properties and transcriptomic landscapes of human natural killer cells derived from bone marrow and umbilical cord blood.

Longitudinal studies have highlighted allogeneic natural killer (NK) cell-based cytotherapy for cancer immunosurveillance and immunotherapy, yet the deficiency of systematic and detailed comparison of NK cells from candidate sources including umbilical cord blood (UC) and bone marrow (BM) largely hinders the large-scale application. Herein, we isolated resident NK cells (rUC-NK, rBM-NK) from mononuclear cells (MNC), and analyzed the corresponding expanded NK cell counterparts (eUC-NK, eBM-NK). Then, the eUC-NK and eBM-NK were turned to multifaceted bioinformatics from the aspects of gene expression profiling and genetic variations. The percentages of total or activated NK cells in rBM-NK group were approximate 2-fold higher over those in the rUC-NK group, respectively. Instead, the proportion of total NK cells in eUC-NK was higher than that in the eBM-NK group, and in particular, the CD25+ memory-like NK cell subset. Furthermore, eUC-NK and eBM-NK manifested multidimensional similarities and diversities in gene expression pattern and genetic spectrum, whereas both eUC-NK and eBM-NK exhibited effective tumor killing capacity. Collectively, we dissected the cellular and transcriptomic signatures of NK cells generated from UC-MNC and BM-MNC, which supplied new literature for further exploring the characteristics of the indicated NK cells and would benefit the clinical application for cancer immunotherapy in future.

Statistical Analysis and Machine Learning Prediction of Disease Outcomes for COVID-19 and Pneumonia Patients.

The Coronavirus Disease 2019 (COVID-19) has spread all over the world and impacted many people's lives. The characteristics of COVID-19 and other types of pneumonia have both similarities and differences, which confused doctors initially to separate and understand them. Here we presented a retrospective analysis for both COVID-19 and other types of pneumonia by combining the COVID-19 clinical data, eICU and MIMIC-III databases. Machine learning models, including logistic regression, random forest, XGBoost and deep learning neural networks, were developed to predict the severity of COVID-19 infections as well as the mortality of pneumonia patients in intensive care units (ICU). Statistical analysis and feature interpretation, including the analysis of two-level attention mechanisms on both temporal and non-temporal features, were utilized to understand the associations between different clinical variables and disease outcomes. For the COVID-19 data, the XGBoost model obtained the best performance on the test set (AUROC = 1.000 and AUPRC = 0.833). On the MIMIC-III and eICU pneumonia datasets, our deep learning model (Bi-LSTM_Attn) was able to identify clinical variables associated with death of pneumonia patients (AUROC = 0.924 and AUPRC = 0.802 for 24-hour observation window and 12-hour prediction window). The results highlighted clinical indicators, such as the lymphocyte counts, that may help the doctors to predict the disease progression and outcomes for both COVID-19 and other types of pneumonia.

Association Among the Gut Microbiome, the Serum Metabolomic Profile and RNA m6A Methylation in Sepsis-Associated Encephalopathy.

Objective: To investigate the relationship among the gut microbiome, serum metabolomic profile and RNA m6A methylation in patients with sepsis-associated encephalopathy (SAE), 16S rDNA technology, metabolomics and gene expression validation were applied. Methods: Serum and feces were collected from patients with and without (SAE group and non-SAE group, respectively, n = 20). The expression of serum markers and IL-6 was detected by enzyme-linked immunosorbent assay (ELISA), and blood clinical indicators were detected using a double antibody sandwich immunochemiluminescence method. The expression of RNA m6A regulator were checked by Q-RTPCR. The gut microbiome was analyzed by 16S rDNA sequencing and the metabolite profile was revealed by liquid chromatography-mass spectrometry (LC-MS/MS). Results: In the SAE group, the IL-6, ICAM-5 and METTL3 levels were significantly more than those in the non-SAE group, while the FTO levels were significantly decreased in the SAE group. The diversity was decreased in the SAE gut microbiome, as characterized by a profound increase in commensals of the Acinetobacter, Methanobrevibacter, and Syner-01 genera, a decrease in [Eubacterium]_hallii_group, while depletion of opportunistic organisms of the Anaerofilum, Catenibacterium, and Senegalimassilia genera were observed in both groups. The abundance of Acinetobacter was positively correlated with the expression of METTL3. The changes between the intestinal flora and the metabolite profile showed a significant correlation. Sphingorhabdus was negatively correlated with 2-ketobutyric acid, 9-decenoic acid, and l-leucine, and positively correlated with Glycyl-Valine [Eubacterium]_hallii_group was positively correlated with 2-methoxy-3-methylpyazine, acetaminophen, and synephrine acetonide. Conclusion: The gut microbiota diversity was decreased. The serum metabolites and expression of RNA m6A regulators in PBMC were significantly changed in the SAE group compared to the non-SAE group. The results revealed that serum and fecal biomarkers could be used for SAE screening.

Exosomes from human induced pluripotent stem cells derived mesenchymal stem cells improved myocardial injury caused by severe acute pancreatitis through activating Akt/Nrf2/HO-1 axis.

Human induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs) have been believed to be a promising alternative for the stem cell transplantation therapy. The exosomes (Exo) from iMSCs play an important role in several kinds of life activities. The role of exosomes from iMSCs in severe acute pancreatitis (SAP) induced myocardial injury (MI) has not been investigated. The Exo were isolated from iMSCs through differential centrifugation method. The SAP rat model was established with 5% sodium taurocholate injection into the distal end of the bilepancreatic duct. RT-PCR and western blotting were used to measure related gene expression. Masson trichrome and Sirius Red stainings were used to evaluate MI injury. Cardiac function was detected through cardiac ultrasound.Exo promoted cell viability through activating Akt/nuclear factor E2 related factors 2 (Nrf2)/heme oxygenase 1 (HO-1) signaling pathway in vitro. Exo improved MI induced by SAP through activating Akt/Nrf2/HO-1 signaling pathway. Exo improved cardiac function, and suppressed oxidative status in the SAP model. Exo increased the expression of von Willebrand Factor (vWF) and vascular endothelial growth factor (VEGF) through activating Nrf2/HO-1 signaling pathway. Our data indicated that the Exo from iMSCs could improve MI caused by SAP through activating Nrf2/HO-1 axis. These findings firstly unfold the potential application of Exo from iMSCs in treating MI induced by SAP.Abbreviations: LVEF: Left ventricular ejection fraction; LVFS: left ventricular fractional shorten; LVDd: left ventricular end-diastolic diameter; LVDs: left ventricular end-systolic diameter; MI: Myocardial infarction; MSCs: Mesenchymal stem cells; iPSCs: Human-induced pluripotent stem cells; SAP: Severe acute pancreatitis; iMSCs: iPSCs derived VEGF: MSCs; vascular endothelial growth factor; Nrf2: Nuclear factor erythroid 2-related factor; RT-PCR: Real-time polymerase chain reaction; HE: Hematoxylin-eosin; MODS: Multiple organ dysfunction syndrome; PI3K: Phosphatidylinositol 3-kinase; SOD: Superoxide dismutase; FBS: Fetal bovine serum; ECL: Enhanced chemiluminescence; IHC: Immunohistochemistry.

Improvement of cardiac function by mesenchymal stem cells derived extracellular vesicles through targeting miR-497/Smad7 axis.

BACKGROUND: The extracellular vesicles (EVs) secreted by bone marrow mesenchymal stromal cells (MSCs) have the ability to improve Myocardial infarction (MI). Some microRNAs (miRNAs) including miR-497 and related target genes have been proved to be closely linked with heart diseases. However, EVs could regulate MI process through miR-497, and the mechanisms have not been fully reported. METHODS: Ligation of left anterior descending artery was performed to established MI animals model. Hypoxia cell model was established through lowering the level of oxygen. The cell invasion, migration, and proliferation were measured using tanswell, wound heating, and MTT assays. HE, Masson trichrome, and Sirius Red staining were used to investigate the morphological changes. RESULTS: Overexpression of miR-497 reversed the promotion of cell migration, invasion, and proliferation caused by EVs. The improvement of cardiac function induced by EVs could also be reversed by overexpression of miR-497. Direct binding site between Smad7 and miR-497 was identified. Knockdown of Smad7 reversed the improvement of cardiac function induced by EVs. CONCLUSIONS: We found that EVs isolated from MSCs might improve the cardiac injury caused by MI through targeting miR497/Smad7. This study provides novel potential therapeutic thought for the prevention and treatment of MI through targeting miR-497/Smad7.

[Clinical study on intravenous combined with aerosol inhalation of polymyxin B for the treatment of pneumonia caused by multidrug-resistant Gram-negative bacteria].

OBJECTIVE: To investigate the efficacy of intravenous combined with aerosol inhalation of polymyxin B for the treatment of pneumonia caused by multidrug-resistant Gram-negative (G-) bacteria. METHODS: A observational study was conducted. The clinical data of 45 patients with pneumonia due to multidrug-resistant G- bacteria admitted to intensive care unit of Fujian Medical University Union Hospital from January to October in 2020 were analyzed. According to the different use methods of polymyxin B, 25 patients who received single intravenous drip (the first dose was 2.0 mg/kg, then 1.25 mg/kg, once every 12 hours) from January to April in 2020 were enrolled in the routine group, and 20 patients who received intravenous drip combined with aerosol inhalation (25 mg once every 12 hours, sputum in the airway was sucked and then sprayed aerosol) from May to October in 2020 were enrolled in the combination group. After the treatment course of polymyxin B, the total bacterial clearance rate, total clinical efficiency rate, recovery time of body temperature, time of bacterial clearance and the change of serum procalcitonin (PCT) level before and after treatment were compared between the two groups. Moreover, the incidence of adverse reactions during treatment in the two groups was observed. RESULTS: The results of sputum culture in the routine group were Acinetobacter baumannii in 13 patients, Klebsiella pneumoniae in 5 patients, Pseudomonas aeruginosa in 6 patients, Enterobacter cloacae in 1 patient; the sputum culture results of the combination group showed that there were 5 patients of Acinetobacter baumannii, 9 Klebsiella pneumoniae and 6 Pseudomonas aeruginosa. There was no significant difference in the results of sputum culture between the two groups (P > 0.05). The total bacterial clearance rate and the total clinical efficiency rate of the combination group were significantly higher than those in the routine group (total bacterial clearance rate: 70.0% vs. 40.0%, total clinical efficiency rate: 75.0% vs. 40.0%, both P < 0.05). The recovery time of body temperature and the time of bacterial clearance of the combination group were significantly shorter than those in the routine group [recovery time of body temperature (days): 6.0±3.9 vs. 10.2±7.3, time of bacterial clearance (days): 6.1±5.2 vs. 11.5±6.8, both P < 0.05]. No significant difference was found in serum PCT level before treatment between the two group. There was no significant difference in serum PCT level before and after treatment in the routine group [µg/L: 0.85 (0.44, 2.87) vs. 1.43 (0.76, 5.30), P > 0.05]. The serum PCT level after treatment in the combination group was significantly lower than that before treatment [µg/L: 0.27 (0.10, 0.70) vs. 0.91 (0.32, 3.53), P < 0.05], and it was significantly lower than that in the routine group [µg/L: 0.27 (0.10, 0.70) vs. 0.85 (0.44, 2.87), P < 0.01]. The incidence of renal toxicity of polymyxin B between the combination group and the routine group was not significantly different (5.0% vs. 4.0%, P > 0.05). CONCLUSIONS: The efficacy of intravenous combined with aerosol inhalation of polymyxin B for the treatment of pneumonia due to multidrug-resistant G- bacteria is better than that of intravenous drip of polymyxin B only. The aerosolized polymyxin B will not increase the risk of renal injury.

SARS-CoV-2 infection induces sustained humoral immune responses in convalescent patients following symptomatic COVID-19.

Long-term antibody responses and neutralizing activities in response to SARS-CoV-2 infection are not yet clear. Here we quantify immunoglobulin M (IgM) and G (IgG) antibodies recognizing the SARS-CoV-2 receptor-binding domain (RBD) of the spike (S) or the nucleocapsid (N) protein, and neutralizing antibodies during a period of 6 months from COVID-19 disease onset in 349 symptomatic COVID-19 patients who were among the first be infected world-wide. The positivity rate and magnitude of IgM-S and IgG-N responses increase rapidly. High levels of IgM-S/N and IgG-S/N at 2-3 weeks after disease onset are associated with virus control and IgG-S titers correlate closely with the capacity to neutralize SARS-CoV-2. Although specific IgM-S/N become undetectable 12 weeks after disease onset in most patients, IgG-S/N titers have an intermediate contraction phase, but stabilize at relatively high levels over the 6 month observation period. At late time points, the positivity rates for binding and neutralizing SARS-CoV-2-specific antibodies are still >70%. These data indicate sustained humoral immunity in recovered patients who had symptomatic COVID-19, suggesting prolonged immunity.

Transcriptomic study of lipopolysaccharide-induced sepsis damage in a mouse heart model.

Sepsis is an emergency systemic illness caused by pathogen infection and the combined result of the underactivity and overactivity of a patient's own immune system. However, the molecular mechanism of this illness remains largely unknown. Lipopolysaccharide (LPS) was injected to establish a sepsis model, and heart tissue was used to analyze transcriptome changes in mice. LPS injection was used to develop a sepsis model, which resulted in cardiac tissue rearrangement and inflammatory response activation. An RNA-sequencing-based transcriptome assay using mouse heart tissue with or without LPS injection showed that 3,326 and 1,769 genes were upregulated and downregulated, respectively (>2-fold changes; P<0.05). Furthermore, these differentially expressed genes were classified into 20 pathways, including 'Wnt signaling pathway', 'VEGF signaling pathway' and 'TGF-ß signaling pathway', and these altered genes were enriched in 41 Gene Ontology terms. The application of Wnt3a inhibited the activation of the LPS-induced inflammatory response and activated Wnt signaling, as well as protecting against LPS-mediated cardiac tissue damage in mice. In contrast, inhibition of Wnt signaling by injection of its inhibitor IWR induced plasminogen activator inhibitor-1 expression and resulted in cardiac structure derangement, which was similar to the symptoms caused by injection of LPS, suggesting that LPS-induced damage to heart tissue may be via inhibition of Wnt signaling. The present analyses showed that Wnt signaling serves a pivotal role in sepsis development and may improve our understanding of the molecular basis underlying sepsis.

MicroRNA-127-5p attenuates severe pneumonia via tumor necrosis factor receptor-associated factor 1.

Pneumonia is a persistent and pervasive disease, the effects of which can be severe. MicroRNA (miR)-127-5p has been utilized as a novel biomarker for the diagnosis of severe pneumonia. The present study aimed to investigate the function of miR-127-5p during severe pneumonia. An in vitro model of severe pneumonia in Ana-1 murine macrophages was established using lipopolysaccharide (LPS). Subsequently, reverse transcription-quantitative PCR and ELISA were performed to detect the mRNA and protein expression levels of interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α. Western blotting was also performed to measure the activity of AKT and NF-κB. The results indicated that compared with the control group, LPS treatment increased TNF receptor-associated factor 1 (TRAF1) expression levels and reduced miR-127-5p expression levels. Furthermore, the results revealed that the 3'-untranslated region of TRAF1 was targeted by miR-127-5p. miR-127-5p mimic reduced LPS-induced increases in IL-1ß, IL-6 and TNF-α expression by targeting TRAF1, which was potentially mediated by inactivation of the AKT and NF-κB signaling pathways. Collectively, the results demonstrated that miR-127-5p may attenuate severe pneumonia by reducing LPS-induced inflammatory cytokine production, and inactivating the AKT and NF-κB signaling pathways by targeting TRAF1.

Changes of hematological and immunological parameters in COVID-19 patients.

The aim of this study was to identify the changes of hematologic and immunological parameters in COVID-19 patients. We collected and analyzed the data of 117 patients who were laboratory confirmed as SARS-CoV-2 infection. The cases were divided into regular group, severe group and critically ill group according to the sixth edition scheme for COVID-19 diagnosis and treatment of China. The laboratory tests included blood routine, cellular and humoral immunity indices, biochemical detections and inflammatory biomarker. Compared with regular patients, severe and critically ill patients had significantly lower lymphocyte count (p < 0.01), decreased red blood cell and hemoglobin (p < 0.01), low levels of immunoglobulin G (p < 0.05) and significantly higher in D-dimer (p < 0.0001), fibrinogen (p < 0.01), white blood cell count (p < 0.01), neutrophil count (p < 0.0001), interleukin-6 (p < 0.05), C-reactive protein (p < 0.01), procalcitonin (p < 0.01), erythrocyte sedimentation rate (p < 0.05), ferritin (p < 0.01) and lactate dehydrogenase (p < 0.0001). The specific immunoglobulin G antibodies to the SARS-CoV-2 in severe and critically ill patients were significantly lower than that in regular patients (p < 0.05). Our findings suggest that the lymphocyte counts, red blood cell counts and the immunoglobulin G antibodies of COVID-19 patients were impaired to varying degrees and the blood was in a state of hypercoagulation, which were more obvious in critically ill patients.

High positive end expiratory pressure levels affect hemodynamics in elderly patients with hypertension admitted to the intensive care unit: a prospective cohort study.

BACKGROUND: To study the effects of different positive end expiratory pressure (PEEP) on blood pressure and heart function in elderly patients with hypertension. METHODS: Forty elderly patients above 65 years of age treated with mechanical ventilation were divided into two groups: a control group of non-hypertensive subjects (n = 18) and a hypertension group (n = 22) patients with essential hypertension. Changes in blood pressure, central venous pressure (CVP), central venous oxygen saturation (ScvO2), heart rate, and airway pressure were determined in response to different selected PEEP levels of 0, 2, 4, 6, 8, 10 and 12 cm H2O under SIMV(PC) + PSV mode throughout the study. RESULTS: In both groups, the increase in PEEP led to an increase in CVP and airway pressure. When PEEP was above 4 cm H2O in the hypertension group, a decrease in blood pressure and ScvO2, and an increase of heart rate were observed. These results indicated that cardiac output significantly decreased. CONCLUSION: High levels of PEEP can significantly influence changes in blood pressure and heart function in elderly patients with hypertension. TRIAL REGISTRATION: This trial was retrospectively registered, The Chinese trial registration number is ChiCTR-ROC-17012873. The date of registration is 10-2-2017.

Morusin alleviates mycoplasma pneumonia via the inhibition of Wnt/ß-catenin and NF-κB signaling.

Morusin has been traditionally used for the treatment of Mycoplasma pneumoniae pneumonia (MPP), but the underlying mechanism remains elusive. The present study aimed to explore the mechanism by which morusin achieves efficacy on mycoplasma pneumonia. Mycoplasma pneumonia model was established in BALB/c mouse and the effects of morusin were evaluated in the model. Compared with the model group, DNA amount of M. pneumoniae decreased by 24.6 ± 3.14% and 47.6 ± 6.78% in low morusin (20 mg/kg) and high morusin (50 mg/kg) groups, respectively (P<0.05). Moreover, morusin treatment led to decreased levels of pro-inflammatory cytokines such as interleukin (IL)-6, IL-1ß, and tumor necrosis factor α and increased level of anti-inflammatory IL-10 in mice lung tissue. Furthermore, morusin treatment inhibited the activation of Wnt/ß-catenin and NF-κB pathways in mice lung tissue. Taken together, our results suggest that morusin relieves mycoplasma pneumonia via the inhibition of the activation of Wnt/ß-catenin and NF-κB pathways, and is a potential natural agent for the treatment of mycoplasma pneumonia.

G-CSF-primed haplo-identical HSCT with intensive immunosuppressive and myelosuppressive treatments does not increase the risk of pre-engraftment bloodstream infection: a multicenter case-control study.

A multicenter retrospective study in 131 patients (44 females/87 males) with hematological disorders who underwent G-CSF-primed/haplo-identical (Haplo-ID) (n = 76) or HLA-identical (HLA-ID) HSCT (n = 55) from February 2013 to February 2016 was conducted to compare the incidence and risk factors for pre-engraftment bloodstream infection (PE-BSI). In the Haplo-ID group, 71/76 patients with high-risk (n = 28) or relapsed/refractory hematological malignancies (n = 43) received FA5-BUCY conditioning (NCT02328950). All received trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis. Blood cultures and catheter tip cultures were obtained to confirm the BSI. PE-BSI was detected in 24/131 HSCT patients (18/76 in Haplo-ID and 6/55 in HLA-ID) after 28 febrile neutropenic episodes. Among 28 isolates for the 24 patients, 21 (75%) were Gneg bacteria, 6 (21.4%) Gpos and 1 (3.6%) fungi. Bacteria sources were central venous line infection (7/29.2%), gastroenteritis (6/25%), lower respiratory tract infection (LRTI; 5/20.8%), perianal skin infection (4/16.7%), and unknown (2/8.3%). The duration of neutropenia (P = 0.046) and previous Gneg bacteremia (P = 0.037) were important risk factors by univariate analysis, while the type of HSCT was not. A trend of TMP-SMX-resistant BSI in both groups may be due to routine antibacterial prophylaxis strategies. Our data show that G-CSF-primed Haplo-ID HSCT did not increase the risk of PE-BSI, even with intensive immunosuppressive treatments.

Long noncoding RNA CNALPTC1 promotes cell proliferation and migration of papillary thyroid cancer via sponging miR-30 family.

Several somatic copy number variations (CNVs) have been identified in papillary thyroid cancer (PTC). However, the functional roles of CNVs and the genes responsible for the roles of CNVs are largely unknown. In this study, we identified a novel long noncoding RNA (lncRNA) CNALPTC1 (copy number amplified long noncoding RNA in papillary thyroid cancer 1). The genomic copy number of CNALPTC1 is amplified and CNALPTC1 expression level is up-regulated in PTC. Increased expression of CNALPTC1 is associated with aggressive clinicopathological characteristics. Gain-of-function and loss-of-function assays revealed that CNALPTC1 promotes proliferation and migration of PTC cells, and inhibits apoptosis of PTC cells. Mechanistically, we found that CNALPTC1 physically associates to miR-30 family and down-regulates miR-30 expression. Furthermore, CNALPTC1 up-regulates the expression of miR-30 targets, such as BCL9, SNAI1, and VIM. The mutation of miR-30 binding site on CNALPTC1 or overexpression of miR-30 abrogates the oncogenic roles of CNALPTC1 in PTC. Collectively, our results suggested that the copy number amplified lncRNA CNALPTC1 promotes PTC progression via sponging miR-30 family. Our data also implied that CNALPTC1 may be a novel therapeutic target for PTC.

Effects of Blood Purification on Serum Levels of Inflammatory Cytokines and Cardiac Function in a Rat Model of Sepsis.

OBJECTIVE: The study aimed to explore the effects of blood purification (BP) on serum levels of inflammatory cytokines and cardiac function in a rat model of sepsis. METHODS: A rat model of sepsis was established by cecal ligation and puncture. All rats were divided into the normal control, sham operation, model, sham treatment, and BP treatment groups. Cardiac functions, inflammatory cytokines, myocardial enzymes, pathological score of cardiac muscle tissue, and myocardial apoptosis of rats in each group were compared. RESULTS: Sepsis rats had higher serum levels of inflammatory cytokines and lower cardiac function than those in the normal control and sham operation groups. Compared with the model and sham treatment groups, improved cardiac functions, decreased inflammatory cytokines, myocardial enzymes, pathological score, and myocardial apoptosis and mortality were observed in the BP treatment group. CONCLUSION: BP may reduce serum levels of inflammatory cytokines and improve cardiac function of sepsis rats.

Association of microRNA polymorphisms with the risk of myocardial infarction in a Chinese population.

MicroRNAs (miRNAs) are involved in the regulation of a variety of biological processes, such as inflammation. Dysregulation of miRNAs have been implicated in many human disease, including cardiovascular diseases. Polymorphisms in miRNA genes may affect the miRNA biogenesis and function, and thus cause changes in the expression of thousands of genes. The aim of this study was to examine whether miRNA polymorphisms (miR-146a rs2910164, miR-149 rs71428439, miR-196a2 rs11614913, miR-218 rs11134527, and miR-499 rs3746444) contribute to the risk for the development of myocardial infarction (MI). Five miRNA polymorphisms were genotyped in a total of 1808 subjects composed of 919 MI patients and 889 control individuals. The GG genotype of rs3746444 was found to be associated with a significantly increased risk of MI (recessive model, adjusted OR = 1.710, 95% CI: 1.058-2.763, P = 0.029). Although the CC genotype of rs2910164 significantly increased the risk of MI under dominant and additive models (P < 0.05), this difference disappeared after adjustment for age, sex, blood pressure, triglycerides, total cholesterol, HDL, LDL and diabetes. In addition, when rs3746444 and rs2910164 were evaluated together by the number of putative high-risk alleles, we found an increased risk of MI for subjects carrying 3-4 risk alleles (3-4 risk alleles vs. 0-1 risk allele, adjusted OR = 1.580, 95% CI: 1.069-2336, P = 0.022; 3-4 risk alleles vs. 0-2 risk allele, adjusted OR = 1.513, 95% CI: 1.031-2.219, P = 0.034). These findings indicate that miR-499 rs3746444 and miR-146a rs2910164 may represent novel markers of MI susceptibility.