Fuzheng Touxie Jiedu Huayu Decoction inhibits the MexAB-OprM efflux pump and quorum sensing-mediated biofilm formation in difficult-to-treat multidrug resistance Pseudomonas aeruginosa.

ETHNOPHARMACOLOGICAL RELEVANCE: Fuzheng Touxie Jiedu Huayu Decoction (FTJHD) is a commonly used clinical formula that has been found effective in resisting multidrug resistance-Pseudomonas aeruginosa in previous in vivo and in vitro studies. AIM OF THE STUDY: To investigate the antimicrobial effects of FTJHD and its drug-containing serum alone or in combination with ceftazidime on difficult-to-treat multidrug resistance-P. aeruginosa (DTMDR-P. aeruginosa). MATERIALS AND METHODS: The antibacterial effects of FTJHD and its drug-containing alone or in combination with ceftazidime against DTMDR-P. aeruginosa were examined by the tube dilution method and bacterial growth curves. The changes in the bacterial ultrastructure were examined by transmission electron microscopy. The biofilm formation ability of bacteria was examined by crystal violet staining and scanning electron microscopy. The expression of the MexAB-OprM efflux pump and quorum sensing system genes were validated through quantitative polymerase chain reaction. Molecular docking was used to evaluate the interaction between active components and the MexAB-OprM efflux pump. RESULTS: FTJHD-containing serums at 1-, 2-, 4-, and 8-fold concentrations reduced the minimal inhibitory concentration (MIC) of ceftazidime against DTMDR-P. aeruginosa from 128 µg/mL to 64 µg/mL. Sub-inhibitory concentrations of ceftazidime in combination with FTJHD and FTJHD-containing serum prolonged the lag period of bacterial growth and reduced bacterial numbers. Additionally, 1/2 MIC of ceftazidime combined with FTJHD-containing serum significantly inhibited the activity of the MexAB-OprM efflux pump and quorum sensing system, thus reducing biofilm formation while causing more severe damage to the bacteria. Molecular docking revealed a strong affinity of quercetin, baicalein, luteolin, kaempferol, and ß-sitosterol for the efflux pump regulatory proteins OprM and MexR. CONCLUSION: FTJHD can exert synergistic anti-DTMDR-P. aeruginosa effects with ceftazidime by inhibiting biofilm formation mediated by the MexAB-OprM efflux pump and quorum sensing.

Analyzing lung cancer risks in patients with impaired pulmonary function through characterization of gut microbiome and metabolites.

BACKGROUND: Lung cancer (LC) is one of the most devastating diseases worldwide, there is growing studies confirm the role of impaired lung function in LC susceptibility. Moreover, gut microbiota dysbiosis is associated with LC severity. Whether alterations in gut microbiota and metabolites are associated with long-term lung dysfunction in LC patients remain unclear. Our study aimed to analyze the risk factors in LC patients with impaired pulmonary function based on the characteristics of the gut microbiome and metabolites. METHODS: Fecal samples from 55 LC patients and 28 benign pulmonary nodules patients were collected. Pulmonary ventilation function was graded according to the American Thoracic Society/ European Respiratory Society (ATS/ERS) method. LC patients were divided into 3 groups, including 20 patients with normal lung ventilation, 23 patients with mild pulmonary ventilation dysfunction and 12 patients with moderate or above pulmonary ventilation dysfunction. The fecal samples were analyzed using 16 S rRNA gene amplicon sequencing and metabolomics. RESULTS: The gut microbiome composition between LC patients and benign pulmonary nodules patients presented clearly differences based on Partial Least Squares Discriminant Analysis (PLS-DA). Pulmonary ventilation function was positively correlated with LC tumor stage, the richness and diversity of the gut microbiota in LC patients with moderate or above pulmonary ventilation dysfunction increased significantly, characterized by increased abundance of Subdoligranulum and Romboutsia. The metabolomics analysis revealed 69 differential metabolites, which were mainly enriched in beta-Alanine metabolism, styrene degradation and pyrimidine metabolism pathway. The area under the curve (AUC) combining the gut microbiome and metabolites was 90% (95% CI: 79-100%), indicating that the two species and four metabolites might regarded as biomarkers to assess the prediction of LC patients with impaired pulmonary function. CONCLUSIONS: Our results showed that microbiome and metabolomics analyses provide important candidate to be used as clinically diagnostic biomarkers and therapeutic targets related to lung cancer with impaired pulmonary function.

Characterizing microbiota and metabolomics analysis to identify candidate biomarkers in lung cancer.

Background: Lung cancer is the leading malignant disease and cause of cancer-related death worldwide. Most patients with lung cancer had insignificant early symptoms so that most of them were diagnosed at an advanced stage. In addition to factors such as smoking, pollution, lung microbiome and its metabolites play vital roles in the development of lung cancer. However, the interaction between lung microbiota and carcinogenesis is lack of systematically characterized and controversial. Therefore, the purpose of this study was to excavate the features of the lung microbiota and metabolites in patients and verify potential biomarkers for lung cancer diagnosis. Methods: Lung tissue flushing solutions and bronchoalveolar lavage fluid samples came from patients with lung cancer and non-lung cancer. The composition and variations of the microbiota and metabolites in samples were explored using muti-omics technologies including 16S rRNA amplicon sequencing, metagenomics and metabolomics. Results: The metabolomics analysis indicated that 40 different metabolites, such as 9,10-DHOME, sphingosine, and cysteinyl-valine, were statistically significant between two groups (VIP > 1 and P < 0.05). These metabolites were significantly enriched into 11 signal pathways including sphingolipid, autophagy and apoptosis signaling pathway (P < 0.05). The analysis of lung microbiota showed that significant changes reflected the decrease of microbial diversity, changes of distribution of microbial taxa, and variability of the correlation networks of lung microbiota in lung cancer patients. In particular, we found that oral commensal microbiota and multiple probiotics might be connected with the occurrence and progression of lung cancer. Moreover, our study found 3 metabolites and 9 species with significantly differences, which might be regarded as the potential clinical diagnostic markers associated with lung cancer. Conclusions: Lung microbiota and metabolites might play important roles in the pathogenesis of lung cancer, and the altered metabolites and microbiota might have the potential to be clinical diagnostic markers and therapeutic targets associated with lung cancer.

Concurrent pigeon paramyxovirus-1 and Acinetobacter baumannii infection in a fatal case of pneumonia.

Pigeon paramyxovirus type 1 (PPMV-1), an antigenic variant of avian paramyxovirus type 1 (APMV-1), mainly infects pigeons. PPMV-1 genotype VI is the dominant genotype infecting pigeons in China. Human infection of avian paramyxovirus was rarely reported, and usually developed mild symptoms, such as conjunctivitis. We detected PPMV-1 in the lower respiratory sample from a fatal case with severe pneumonia; this patient aged 64 years presented cough, fever, and haemoptysis for 8 days and was admitted to hospital on Dec 26, 2020. He developed acute respiratory distress syndrome and sepsis in the following days and died of multiple organ failure on Jan 7, 2021. Sputum and blood culture reported multidrug-resistant Acinetobacter baumannii (ABA) for samples collected on days 22 and 19 post-illness, respectively. However, clinical metagenomic sequencing further reported PPMV-1 besides ABA in the bronchoalveolar lavage fluid. The PPMV-1 genome showed 99.21% identity with a Chinese strain and belonged to VI genotype by BLAST analysis. Multiple basic amino acids were observed at the cleavage site of F protein (113RKKRF117), which indicated high virulence of this PPMV-1 strain to poultry. The patient had close contact with pigeons before his illness, and PPMV-1 nucleic acid was detected from the pigeon feather. PPMV antibody was also detected in the patient serum 20 days after illness. In conclusion, concurrent PPMV-1 genotype VI.2.1.1.2.2 and ABA infection were identified in a fatal pneumonia case, and cross-species transmission of PPMV-1 may occur between infected pigeons and the human being.

[Network pharmacological analysis and experimental study of Pulsatilla chinensis against inflammatory injury caused by pneumonia in mice infected with influenza virus FM_1].

Network pharmacology and the mouse model of viral pneumonia caused by influenza virus FM_1 were employed to explore the main active components and the mechanism of Pulsatilla chinensis against the inflammatory injury of influenza virus-induced pneumonia. The components and targets of P. chinensis were searched from TCMSP, and the targets associated with influenza virus-induced pneumonia were searched from GeneCards. The common targets between P. chinensis and influenza virus-induced pneumonia were identified with Venn diagram established in Venny 2.1. The herb-component-disease-target(H-C-D-T) network was constructed by Cytoscape 3.7.2. The above data were imported into STRING for PPI network analysis. Gene Ontology(GO) enrichment and KEGG pathway enrichment were performed with DAVID. BALB/cAnN mice were infected with the influenza virus FM_1 by nasal drip to gene-rate the mouse model of pneumonia. Immunohistochemistry was adopted to the expression profiling of inflammatory cytokines in the lung tissues of mice in the blank group, model group, and P. chinensis group 1, 3, 5, and 7 days after infection. The pathological changes of lung and trachea of mice in blank group, model group, and P. chinensis group were observed with light microscope and scanning electron microscope at all the time points. The network pharmacological analysis indicated that 9 compounds of P. chinensis were screened out, with a total of 57 targets, 22 of which were overlapped with those of influenza virus-induced pneumonia. A total of 112 GO terms(P<0.05) were enriched, including 81 terms of biological processes, 11 terms of cell components, and 20 terms of molecular functions. A total of 53 KEGG signaling pathways(P<0.05) were enriched, including TNF signaling pathway, influenza A signaling pathway, NF-κB signaling pathway, MAPK signaling pathway and other signaling pathways related to influenza/inflammation. In the P. chinensis group, the expression of TNF-α and IL-1 in the lung tissue was down-regulated on the 3 rd day after infection, and that of IL-6 in the lung tissue was down-regulated on the 5 th day after infection. Light microscopy and scanning electron microscopy showed that P. chinensis significantly alleviated the pathological damage of lung and trachea compared with the model group. This study reflects the multi-components, multi-targets, and multi-pathways of P. chinensis against influenza virus-induced pneumonia. P. chinensis may reduce the production of proinflammatory cytokines and mediators and block the pro-inflammatory signaling pathways to alleviate viral pneumonia, which provides reference for future research.

Sirolimus combined with oseltamivir and corticosteroid treatment for a puerpera with severe pneumonia caused by 2009 pandemic H1N1: A case report.

Severe pneumonia in patients infected with the 2009 pandemic H1N1 (pH1N1) virus was partially attributed to excessive immune response. Anti-virus treatment for these patients was insufficient. Here we reported the therapy effect of sirolimus, an immunosuppressor, combined with oseltamivir and corticosteroid for a puerpera with severe pneumonia caused by pH1N1 virus. This patient has infected with the pH1N1 virus in late pregnancy, and antiviral therapy was not implemented timely. She developed severe pneumonia and ARDS rapidly and need receive a cesarean section on the 39th week after pregnancy. After giving birth to a healthy baby, she received a combination of oseltamivir, sirolimus and corticosteroid, and improved in the following days. Moreover, the cytokines in serum and viral loads in BALF decreased significantly. She recovered without infectious symptoms and was discharged. Sirolimus combined with oseltamivir and corticosteroid is likely responsible for lowering the viral loads, reducing the patient's cytokine level, and further improving her clinical outcomes. It provides evidence that adjuvant treatment was beneficial to patients with severe pneumonia induced by the pH1N1 virus.

Effect of PDCA-based nursing management model on the quality of life and complications of patients with acute leukemia undergoing chemotherapy.

OBJECTIVE: To assess the influence of PDCA-based nursing management model on the quality of life (QOL) and complications of patients with acute leukemia undergoing chemotherapy. METHODS: In this study, we randomly divided 118 patients with acute leukemia undergoing chemotherapy in our hospital into an observation group (n=59) and a control group (n=59). The control group was implemented routine nursing while the observation group was implemented PDCA-based nursing management. The anxiety, depression, QOL, cancer fatigue, total complication rate, sleep quality, and patients' satisfaction were compared between the two groups. RESULTS: The SAS and SDS scores of the observation group were significantly lower than those of the control group (P<0.05). The scores of physical function, general health, social function, emotional role, and mental health of the observation group were superior to those of the control group (all P<0.05). The 4 dimensions of behavior/severity, sense, emotion and cognition/mood in the observation group were significantly lower than those of the control group (all P<0.05). The incidence of complications such as nausea and vomiting, infection, bleeding, phlebitis, bone marrow suppression and mucositis in the observation group was significantly lower than that in the control group (P<0.05). The scores of sleep quality in the observation group were significantly lower than those of the control group (all P<0.05). The observation group's satisfaction with PDCA-based nursing management was markedly higher than that of the control group (P<0.05). CONCLUSION: The PDCA-based nursing management model applied to patients with acute leukemia undergoing chemotherapy has shown good effects, which can improve depression, anxiety, cancer fatigue, sleep quality and QOL. It also significantly reduced the incidence of complications and improved patients' satisfaction, which was worth of clinical application.

CdS Nanorods Anchored with Crystalline FeP Nanoparticles for Efficient Photocatalytic Formic Acid Dehydrogenation.

Photocatalytic dehydrogenation of formic acid is a promising strategy for H2 generation. In this work, we report the use of crystalline iron phosphide (FeP) nanoparticles as an efficient and robust cocatalyst on CdS nanorods (FeP@CdS) for highly efficient photocatalytic formic acid dehydrogenation. The optimal H2 evolution rate can reach ∼556 µmol·h-1 at pH 3.5, which is more than 37 times higher than that of bare CdS. Moreover, the photocatalyst demonstrates excellent stability; no significant decrease of the catalytic activity was observed during continuous testing for more than four days. The apparent quantum yield is ∼54% at 420 nm, which is among the highest values obtained using noble-metal-free photocatalysts for formic acid dehydrogenation. This work provides a novel strategy for designing highly efficient and economically viable photocatalysts for formic acid dehydrogenation.

Homogeneous Molecular Iron Catalysts for Direct Photocatalytic Conversion of Formic Acid to Syngas (CO+H2 ).

The catalytic decomposition of formic acid to generate syngas (a mixture of H2 and CO) is a highly valuable strategy for energy conversion. Syngas can be used directly in internal combustion engines or can be converted to liquid fuels, meeting future energy challenges in a sustainable manner. Herein, we report the use of homogeneous molecular iron catalysts combined with a CdS nanorods (NRs) semiconductor to construct a highly efficient photocatalytic system for direct conversion of formic acid to syngas at room temperature and atmospheric pressure. Under optimal conditions, the photocatalytic system presents an activity of 150 mmol gcatalyst -1 h-1 towards H2 , and an apparent quantum yield (AQY) of 16.8 %, making it among the most active noble-metal-free photocatalytic systems for H2 evolution from formic acid under visible light. Meanwhile, these iron-based molecular catalysts also demonstrate remarkable enhancement in CO evolution with robust stability. The mechanistic role of the molecular catalyst is further investigated by using cyclic voltammetry, which suggests the formation of FeI species as the key step in the catalytic conversion of formic acid to syngas.

[Effect of Scutellariae Radix on expression of inflammatory cytokine protein and gene in lung of mice with viral pneumonia caused by influenza virus FM1 infection].

Mice models of viral pneumonia were induced by pulmonary adaptive strain FM1 of influenza A virus in Asian mice.RT-PCR and immunohistochemistry were used to dynamically observe the effect of Scutellariae Radix on the protein and gene expression of inflammatory cytokine in the lungs of the model mice infected by influenza virus FM1 at different phases. The partial mechanism of Scutellariae Radix in repairing the immune inflammatory damage of target organs of pneumonia caused by influenza virus was further explored. The results showed that Scutellariae Radix reduced protein and gene expression of proinflammatory cytokines tumor necrosis factor( TNF-α),interleukin IL-1,IL-6 in lung tissues from 3 rd to 5 th day after infection,and increased protein and gene expression of IL-10 and IFN-γ in lung tissues on the 5 th day after infection. Scutellariae Radix may inhibit excessive release of pro-inflammatory cytokines and promote the expression of anti-inflammatory cytokines,thereby inhibiting the systemic inflammatory response syndrome,reducing the immunoinflammatory pathological damage of lung caused by influenza virus FM1 infection,and promoting lung repair of tissue inflammatory lesions.

Ursolic acid benzaldehyde chalcone, leads to inhibition of cell proliferation and arrests cycle in G1/G0 phase in colon cancer.

The present study investigates the effect of matrine on colon cancer cell viability and apoptosis and tumor growth in mice xenograft model. The results from MTT assay revealed a concentration and time dependent reduction in viability of HCT8 and HT29 colon cancer cells by matrine. The viability of HCT8 and HT29 cells was reduced to 24.67 and 29.32% on treatment with 4 µM/ml concentration of matrine after 48 h (P < 0.05). The results from flow cytometry revealed increase in population of HCT8 and HT29 cells to 77.6 ± 0.3 and 54.0 ± 5.4%, respectively compared to 1.4 ± 0.3 and 2.4 ± 0.7% in control on exposure to 1 µM/ml concentration of matrine. Histone H2AX phosphorylation and expression of Myt1, cyclin A2, cyclin B1 and p53 were increased in HCT8 and HT29 cells on treatment with matrine for 48 h. Matrine treatment also increased the phosphorylation of cdc2 significantly compared to control cells at 48 h (P < 0.05). Results from Annexin-V/FITC-staining showed increase in proportion of apoptotic cells in HCT8 and HT29 cells 67.52 and 68.56 on treatment with 1 µM/ml of matrine. Matrine treatment caused a marked reduction in the growth of HCT8 cell xenograft after 21 days. Thus matrine inhibits cell viability, induces apoptosis and inhibits tumor growth in colon cancer.

Serum Salusin-ß Levels Are Correlated with Slow Coronary Flow.

CONTEXT: Slow coronary flow (SCF) is a special coronary microvascular disorder associated with recurrent chest pain. The pathogenesis of SCF remain unclear. OBJECTIVES: We sought to assess whether serum salusin-ß levels are correlated with SCF. METHODS: We enrolled 76 patients with angiographically confirmed SCF and 108 age- and gender-matched controls. We measured serum salusin-ß levels by enzyme-linked immunosorbent assay and coronary flow rate was assessed using thrombolysis in myocardial infarction frame count (TFC). RESULTS: Serum salusin-ß levels were elevated in SCF patients compared with controls (4.33 [range 3.52-5.87] nmol/L vs. 3.76 [range 2.98-4.67] nmol/L). Multivariate logistic regression analysis revealed that salusin-ß in serum was the independent predictor of SCF (odds ratio = 1.814). Serum salusin-ß levels were independently correlated with mean-TFC (r = 0.355, p = 0.002). CONCLUSIONS: Serum salusin-ß levels were independently associated with SCF. Therefore, our findings implicate a potential role of salusin-ß in the pathophysiology of SCF and provide insights on both risk stratification and modification in this patient population.

Expression of claudin-5, -7, -8 and -9 in cervical carcinoma tissues and adjacent non-neoplastic tissues.

Recent data indicate that the tight junction proteins are abnormally regulated in several human cancers and the expression of these proteins is involved in the etiology and progression of cancer. To explore the expression distinction of the tight junction proteins claudin-5, -7, -8 and -9 in the adjacent non-neoplastic tissues and cervical carcinoma tissues, 72 cervical carcinoma tissues and the samples of non-neoplastic tissues adjacent to the tumors were examined for expression of claudin-5, -7, -8 and -9 by streptavidin-perosidase immunohistochemical staining method. The positive expression rates of claudin-5 in cervical carcinoma tissues and adjacent non-neoplastic tissues were 31.9% (23/72) and 51.4% (37/72) respectively (P < 0.05). The positive expression rates of claudin-7 in cervical carcinoma tissues and adjacent non-neoplastic tissues were 47.2% and 50.0% respectively (P = 1.000). The positive expression rates of claudin-8 in cervical carcinoma tissues and adjacent non-neoplastic tissues were 54.2 % and 27.8% respectively (P < 0.01). The positive expression rates of claudin-9 in cervical carcinoma tissues and adjacent non-neoplastic tissues were 38.9% and 56.9% respectively (P < 0.05). Thus in our study, the expression of claudin-5 and claudin-9 was down-regulated while the expression of claudin-8 was up-regulated in cervical carcinoma tissues compared with adjacent non-neoplastic tissues. The expression of claudin-7 has no obviously difference between cervical carcinoma tissues and adjacent non-neoplastic tissues. In addition, correlations between claudin-5, -8 and -9 expression with lymphatic metastasis were observed. Our study reveals that the expression of claudin-5, -8 and -9 altered between in cervical carcinoma tissues and adjacent non-neoplastic tissues.

[The influence of representative herbs of clearing and detoxifying drugs effect on inflammatory cytokines expression of mice lung homogenate infected by influenza virus FM1].

OBJECTIVE: In order to screen out a certain kind of traditional medicine which has a better role in immune regulatory, the influence of representatives of heat clearing and detoxicating herb on inflammatory cytokines protein expression of mice lung homogenate infected by FM1 have been observed. METHOD: Modeling mice infected by FM1. On the first, third, fifth and seventh day after FM1 infection, tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-10 (IL-10), and gamma-interferon (IFN-gamma) expression in mice lung homogenate of normal control group, model control group, scutellari group, isatidis group, pulsatilla group, polygonum cuspidatum group and oldenlandia group have been tested by ELISA method. RESULT: The expression of TNF-alpha, IL-6, IFN-gamma and IL-10 in mice lung homogenate reaches its peak on the third day after FM1 infection, significantly higher than the control group (P < 0.05). Scutellari and isatidis are two representatives of heat clearing and detoxicating herb, which can decrease the expression of TNF-alpha, IL-6 and IL-1 and increase the expression of IL-10, IFN-gamma. The effect are more pronounced and statistically significant (P < 0.05) on the third and fifth day after infection, pulsatilla, polygonum cuspidatum and oldenlandia can also regulate the inflammatory cytokines, but the effect are not so obvious as scutellari and isatidis. CONCLUSION: Scutellari and isatidis, two representatives of heat clearing and detoxicating herb, have a good intervention on immune damage caused by influenza virus through adjusting the balance of inflammatory cytokines and anti-inflammatory cytokines.