An interesting electrocardiogram caused by lead reversal.

BACKGROUND: During normal sinus rhythm, atrial depolarization is conducted from right atrium to left atrium through Bachmann's bundle, and a normal P wave axis which is measured on the frontal plane is between 0º and + 75º. The change of P wave polarity is helpful for the analysis of origin point. CASE PRESENTATION: We report a patient with negative P wave in lead I. The characteristics of QRS complex in leads V1 to V6 are helpful to preliminarily differential diagnosis. The 12-lead electrocardiogram (ECG) with correct limb leads (right arm-left arm) placement shows sinus rhythm with complete right bundle branch block (RBBB). CONCLUSIONS: The change of P wave polarity as well as characteristics of QRS complex can help identify limb-lead reversals.

Association between admission heart rate and in-hospital mortality in patients with acute exacerbation of chronic obstructive pulmonary disease and respiratory failure: a retrospective cohort study.

BACKGROUND: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) combined with respiratory failure (RF) is a chronic respiratory disease that seriously endangers human health. This study aimed to specifically evaluate the relationship between admission heart rate (AHR) and in-hospital mortality in patients with combined AECOPD and RF to better inform clinical treatment. METHODS: This retrospective cohort study included 397 patients admitted to a Chinese hospital between January 2021 and March 2023. The primary outcome measure was all-cause in-hospital mortality. Multivariate logistic regression analyses were performed to calculate adjusted hazard ratios (OR) with corresponding 95% confidence intervals (CI), and curve fitting and threshold effect were performed to address nonlinear relationships. RESULTS: In total, 397 patients with AECOPD/RF were screened. The mean (± SD) age of the study cohort was 72.6 ± 9.5 years, approximately 49.4% was female, and the overall in-hospital mortality rate was 5%. Multivariate logistic regression analysis and smooth curve fitting revealed a nonlinear association between AHR and in-hospital mortality in the study population, with 100 beats/min representing the inflection point. Left of the inflection point, the effect size (OR) was 0.474 (95% CI 0.016 ~ 13.683; p = 0.6635). On the right side, each 1 beat/min increase in AHR resulted in an effect size (OR) of 1.094 (95% CI 1.01 ~ 1.186; p = 0.0281). CONCLUSIONS: Results of the present study demonstrated a nonlinear relationship between AHR and in-hospital mortality in patients with AECOPD/RF. When AHR was < 100 beats/min, it was not statistically significant; however, AHR > 100 beats/min was a predictor of potential mortality, which increased by 9.4% for every 1 beat/min increase in AHR.

Berberine Alleviates Gastroesophageal Reflux-Induced Airway Hyperresponsiveness in a Transient Receptor Potential A1-Dependent Manner.

Background: To investigate the beneficial effect of berberine on gastroesophageal reflux-induced airway hyperresponsiveness (GERAHR) and explore the underlying mechanism. Methods: Coword cluster analysis and strategic coordinates were used to identify hotspots for GERAHR research, and an online tool (STRING, https://string-db.org/) was used to predict the potential relationships between proteins. Guinea pigs with chemically induced GERAHR received PBS or different berberine-based treatments to evaluate the therapeutic effect of berberine and characterize the underlying mechanism. Airway responsiveness was assessed using a plethysmography system, and protein expression was evaluated by western blotting, immunohistochemical staining, and quantitative PCR analysis. Results: Bioinformatics analyses revealed that TRP channels are hotspots of GERAHR research, and TRPA1 is related to the proinflammatory neuropeptide substance P (SP). Berberine, especially at the middle dose tested (MB, 150 mg/kg), significantly improved lung function, suppressed inflammatory cell infiltration, and protected inflammation-driven tissue damage in the lung, trachea, esophagus, and nerve tissues in GERAHR guinea pigs. MB reduced the expression of TRPA1, SP, and tumor necrosis factor-alpha (TNF-α) in evaluated organs and tissues. Meanwhile, the MB-mediated protective effects were attenuated by simultaneous TRPA1 activation. Conclusions: Mechanistically, berberine was found to suppress GERAHR-induced upregulation of TRPA1, SP, and TNF-α in many tissues. Our study has highlighted the potential therapeutic value of berberine for the treatment of GERAHR.

RIOK1 is associated with non-small cell lung cancer clinical characters and contributes to cancer progression.

Lung cancer is one of the most common malignant tumors and is currently the leading cause of cancer-related deaths worldwide. Although the treatment strategy has been significantly improved, the prognosis of lung cancer patients is still quite poor. RIOK1 has been reported to be highly expressed in non-small cell lung cancer (NSCLC), however, its clinical significance and biological function are still largely unknown in lung cancer. Using western blot and immunohistochemistry, we showed that RIOK1 was highly expressed in NSCLC tissues and correlated with advanced stage and poor prognosis. Furthermore, knockdown of RIOK1 could inhibit proliferation, migration, and invasion in NSCLC cells and tumorigenesis in vivo through AKT, Cyclin B1, MMP2, and EMT pathway. Furthermore, cell viability and apoptosis assays demonstrated that RIOK1 maintained NSCLC cell survival and reduced apoptosis rate when cells were treated with cisplatin. Western blot analysis demonstrated that RIOK1 depletion caused up-regulated protein expression of cleaved PARP and Caspase-3 in NSCLC cells. These findings revealed a novel function of RIOK1 in non-small cell lung cancer progression and suggest that RIOK1 might become a promising diagnostic and therapeutic target for this disease.

Gentiopicroside ameliorates ovalbumin-induced airway inflammation in a mouse model of allergic asthma via regulating SIRT1/NF-κB signaling pathway.

Allergic asthma is a common airway inflammatory disorder with increasing morbidity and mortality worldwide. Gentiopicroside (GPS) is a secoiridoid glycoside compound that exhibits anti-inflammatory property. However, the effect of GPS on allergic asthma has not been reported yet. In this study, we investigated the role of GPS in a mouse model of ovalbumin (OVA)-induced allergic asthma and explored its potential mechanism. Mice were sensitized with OVA and gavaged with 20, 40, or 80 mg/kg GPS. Administration of GPS decreased lung wet-to-dry weight ratio. Histological analysis of H&E and PAS staining showed that GPS treatment alleviated inflammatory cell infiltration and goblet cell hyperplasia in lung tissue of OVA-sensitized mice. Moreover, GPS inhibited the recruitment of inflammatory cells including total cells, macrophages, eosinophils, lymphocytes and neutrophils and the secretion of T helper type 2 (Th2) cytokines (interleukin (IL)-4, IL-5 and IL-13) in bronchoalveolar lavage fluid (BALF) of OVA-sensitized mice in a dose dependent manner. The levels of OVA-specific immunoglobulin E (IgE) and pro-inflammatory tumor necrosis factor (TNF)-α were also attenuated by GPS treatment. Interestingly, GPS upregulated the expression of silent information regulator 1 (SIRT1) while downregulated the expression of acetyl-nuclear factor kappa B (NF-κB) p65 in lung tissue of OVA-sensitized mice. Furthermore, treatment with an SIRT1 inhibitor (EX-527) partially abolished the inhibitory effect of GPS on OVA-induced airway inflammation, suggesting that the anti-inflammation of GPS might be achieved through regulating SIRT1/NF-κB p65 signaling pathway. These findings indicate that GPS might be a novel drug candidate in the treatment of allergic asthma.

Clinical features related to hospital expenses for non-cystic fibrosis bronchiectasis in China.

OBJECTIVE: Bronchiectasis is a common chronic airway disease. We investigated the economic burden and associated factors of bronchiectasis in China. METHODS: In this multicenter retrospective cohort study, we reviewed medical records of patients admitted to 18 tertiary hospitals during 2010 to 2014 with a bronchiectasis-related diagnosis. RESULTS: A total 5469 patients with bronchiectasis were admitted, accounting for 3.13% ± 1.80% of all discharged patients with any diagnosis during the same period; 13 patients died upon discharge. The median hospitalization cost was RMB 8421.52 (RMB 5849.88-12,294.47). Risk factors associated with hospitalization costs included age at admission (>70 vs. <40 years, odds ratio (OR) = 1.221, 95% confidence interval (CI) = 1.082-1.379; >80 vs. <40 years, OR = 1.251, 95% CI = 1.089-1.438), smoking (≤15 packs/year vs. non-smokers, OR = 1.125, 95% CI = 1.006-1.271; >15 packs/year vs. non-smokers, OR = 1.127, 95% CI = 1.062-1.228), length of hospitalization (OR = 1.05, 95% CI = 1.046-1.054), combination antibiotic treatment (OR = 1.089, 95% CI = 1.033-1.148), cough (OR = 0.851, 95% CI = 0.751-0.965), dyspnea (OR = 0.93, 95% CI = 0.878-0.984), chronic obstructive pulmonary disease (OR = 0.935, 95% CI = 0.878-0.996), respiratory failure (OR = 0.923, 95% CI = 0.862-0.989), cor pulmonale (OR = 0.919, 95% CI = 0.859-0.982), and death (OR = 1.816, 95% CI = 1.113-2.838). CONCLUSIONS: Age, smoking status, symptoms, and respiratory comorbidities were associated with hospitalization costs of bronchiectasis.

miR-1323 Promotes Cell Migration in Lung Adenocarcinoma by Targeting Cbl-b and Is an Early Prognostic Biomarker.

Purpose: MicroRNAs are known to regulate cellular processes in non-small cell lung cancer (NSCLC) cells and predict prognosis. However, identification of specific microRNAs in NSCLC as potential therapeutic targets is controversial. We aim to determine the clinical significance of miR-1323 in the prognosis of patients with lung cancer and the potential mechanism. Patients and methods: A bioinformatics approach was used to screen the importance microRNA in NSCLC through the online GEO database (GSE42425). The relationship between expression level of miR-1323 and overall survival of lung cancer patients was analyzed. Additionally, an independent corhort including 53 NSCLC cases that underwent resection validated the connection between miR-1323 and LUAD patients' overall survival. Next, the function of miR-1323 was studied in vitro by transient transfection. A more in-depth mechanism was studied through luciferase reporter gene experiments. Results: High miR-1323 expression correlated with poor survival in NSCLC patients (P = 0.011), and in lung adenocarcinoma (LUAD) patients (P = 0.015) based on GEO database (GSE42425). In the independent cohort based on our hospital, high miR-1323 expression was associated with LUAD patients (P = 0.025). Moreover, transfection with mimics of miR-1323 showed an increased migratory capacity in LUAD A549 and HCC827 cells. In addition, E3 ubiquitin-protein ligase Casitas B-lineage Lymphoma-b (Cbl-b) was found to be the target genes of miR-1323 and significantly down regulated after mimics of miR-1323 transfection, and high Cbl-b expression predicted better prognosis in NSCLC and LUAD (P = 0.00072 and P = 0.02, respectively). Conclusion: The miR-1323 promoted LUAD migration through inhibiting Cbl-b expression. High miR-1323 expression predicted poor prognosis in LUAD patients.

Altered mast cell activity in response to rhinovirus infection provides novel insight into asthma.

Objective: Human rhinoviruses (RVs) are a type of common respiratory virus capable of inducing an asthma attack. Although mast cells are important effector cells involved in allergic disease, little is known about the direct effects of an RV infection on mast cells. The aim of this study is to investigate mast cell behavior in response to RV infection and gain insight into the effects of RVs on mast cells. Methods: Viral replication, cell viability, apoptosis and cytokine release were quantified in Human mast cell-1 (HMC-1) cells following RV16 infection. Results: The results revealed that the viral RNA copy number increased substantially over time. Intercellular cell adhesion molecule-1 (ICAM-1) transcripts were significantly upregulated from 1.79 to 6.37 times following RV16 infection compared to the controls (p ≤ 0.05). Lactate dehydrogenase (LDH) activity was significantly increased, whereas the cell viability decreased following RV16 infection. Examination of the early cellular response to infection revealed that RV16 increased caspase 3 activity and aggravated apoptotic responses. Furthermore, detection of the innate immune response to RV infection revealed that the release of IL-6, IL-8, TNF-α, and IFN-α by HMC-1 cells increased significantly compared to the control groups. Conclusions: RV infection influences mast cell functionality and promotes the innate immune response of mast cells following viral infection. These results provide a novel insight which mast cells have the potential to be involved in the pathogenesis of RV-induced exacerbations of asthma.

[Human rhinovirus infection promotes mast cell apoptosis and increases the release of inflammatory cytokines].

Objective To investigate the regulation of innate immune response of HMC-1 mast cells to human rhinovirus (HRV) infection. Methods Virus replication in HMC-1 cells was quantified by real-time quantitative PCR (qRT-PCR). Cell viability and apoptosis were assessed by flow cytometry. The levels of tumor necrosis factor α (TNF-α), interferon α (IFN-α), interleukin 6 (IL-6) and IL-8 produced by HMC-1 cells were measured using ELISA. Results After HRV infected HMC-1 cells, the copy numbers of virus RNA and apoptotic cells increased obviously over time, what's more, the release of TNF-α, IFN-α, IL-6 and IL-8 from HMC-1 cells ascended significantly compared with control groups. Conclusion HRV infection can promote mast cell apoptosis and enhance the release of inflammatory cytokines from mast cells.

Electrocardiogram: his bundle potentials can be recorded noninvasively beat by beat on surface electrocardiogram.

BACKGROUND: The micro waveform of His bundle potential can't be recorded beat-to-beat on surface electrocardiogram yet. We have found that the micro-wavelets before QRS complex may be related to atrioventricular conduction system potentials. This study is to explore the possibility of His bundle potential can be noninvasively recorded on surface electrocardiogram. METHODS: We randomized 65 patients undergoing radiofrequency catheter ablation of paroxysmal superventricular tachycardia (exclude overt Wolff-Parkinson-White syndrome) to receive "conventional electrocardiogram" and "new electrocardiogram" before the procedure. His bundle electrogram was collected during the procedure. Comparative analysis of PAs (PA interval recorded on surface electrocardiogram), AHs (AH interval recorded on surface electrocardiogram) and HVs (HV interval recorded on surface electrocardiogram) interval recorded on surface "new electrocardiogram" and PA, AH, HV interval recorded on His bundle electrogram was investigated. RESULTS: There was no difference (P > 0.05) between groups in HVs interval (49.63 ± 6.19 ms) and HV interval (49.35 ± 6.49 ms). Results of correlational analysis found that HVS interval was significantly positively associated with HV interval (r = 0.929; P < 0.01). CONCLUSIONS: His bundle potentials can be noninvasively recorded on surface electrocardiogram. Noninvasive His bundle potential tracing might represent a new method for locating the site of atrioventricular block and identifying the origin of a wide QRS complex.

Prediction of Pulmonary Arterial Hypertension in Chronic Obstructive Lung Disease from Three-Dimensional Vectorcardiographic Parameters.

AIM: The objective of our study was to assess diagnostic value of three-dimensional (3D) vectorcardiographic (VCG) parameters in detecting pulmonary arterial hypertension (PAH) in chronic obstructive lung disease (COLD) with and without right ventricular hypertrophy (RVH). METHODS: The study group of 62 patients with COPD was stratified on the basis of color Doppler echocardiographic findings into three subgroups: non-PAH (n = 23), PAH without RVH (n = 22), and PAH with RVH (n = 17). Pairwise differences between the subgroups were evaluated by one-way analysis of variance, and Pearson correlation analysis was used to evaluate the significance of the correlations between pulmonary arterial systolic pressure (PASP) and various VCG parameters. RESULTS: The azimuth of the QRS vector decreased from -24° in the non-PAH group to -62° in PAH without RVH and to -140° in PAH with RVH (P < 0.01 for pairwise differences between all three groups). Similar significant decrease was observed for the azimuth of the ventricular gradient (VG) vector. Spatial QRS/T angle increased from 69° in the non-PAH group to 115° in PAH without RVH (P < 0.01). In the PAH group with RVH, QRS/T angle was 94° (P < 0.05 for difference from the non-PAH group). There was a significant correlation between PASP and QRS/T angle (r = 0.89, P < 0.05) and between PASP and the azimuth of the VG vector (r = 0.86, P < 0.05). PASP increase from linear regression model was 0.8 mmHg for a QRS/T angle increase by 10° and 1.3 mmHg for each 10° increase in the azimuth of the VG vector. CONCLUSION: 3DVCG parameters are potentially useful for predicting PASP in COLD patients, and possibly also for differentiation between COLD patients with PAH and RVH from those without RVH.

Pseudomonas pyocyanin stimulates IL-8 expression through MAPK and NF-κB pathways in differentiated U937 cells.

BACKGROUND: Pyocyanin (PCN), an extracellular product of Pseudomonas aeruginosa and a blue redox active secondary metabolite, plays an important role in invasive pulmonary infection. However, the detailed inflammatory response triggered by PCN infection in inflammatory cells (particularly macrophages), if present, remains to be clarified. To investigate the effects of PCN on macrophages, the ability of PCN to induce inflammation reaction and the signaling pathway for IL-8 release in PCN-induced differentiated U937 cells were examined. RESULTS: It was found that PCN increased IL-8 release and mRNA expression in Phorbol 12-myristate 13-acetate (PMA) differentiated U937 cells in both a concentration- and time-dependent manner by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). P38 and ERK MAPKs were activated after 10 min of induction with PCN and their levels returned to baselines after 30 min by Western blotting. It was also found that within 10 min of PCN incubation, the level of p-I-κBα in the cytosol was increased, which returned to baseline level after 60 min. Meanwhile, the level of p-p65 was increased in the nuclear extract and cytosol, and maintained high in total cell lysates. The results were further confirmed by the observation that p38, ERK1/2 and NF-κB inhibitors inhibited PCN-induced NF-κB activation and attenuated PCN-induced IL-8 expression in U937 cells as a function of their concentrations. Moreover, it was shown that PCN induced oxidative stress in U937 cells and N-acetyl cysteine, an antioxidant, was able to inhibit PCN-induced IL-8 protein expression. CONCLUSIONS: It is concluded that PCN induces IL-8 secretion and mRNA expression in PMA-differentiated U937 cells in a concentration- and time- dependent manner. Furthermore, p38 and ERK MAPKs and NF-κΒ signaling pathways may be involved in the expression of IL-8 in PCN-incubated PMA-differentiated U937 cells.

Pyocyanin from Pseudomonas induces IL-8 production through the PKC and NF-κB pathways in U937 cells.

Pyocyanin, an extracellular product of Pseudomonas aeruginosa (P. aeruginosa), is important in invasive pulmonary infection. Pseudomonas infections are characterized by a marked influx of polymorphonuclear cells (neutrophils). An increased release of interleukin-8 (IL-8), a potent neutrophil chemoattractant, in response to pyocyanin may contribute to the marked infiltration of neutrophils and subsequent neutrophil-mediated tissue damage observed in Pseudomonas-associated lung diseases. In order to explore the pathogenesis of pyocyanin on macrophages, we treated phorbol-12-myristate-13-acetate (PMA)-differentiated U937 cells with pyocyanin in vitro and explored the expression of IL-8 using reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). In the present study, we also investigated the activation of protein kinase C (PKC) and nuclear factor (NF)-κB in PMA-differentiated U937 cells by western blotting and immunohistochemical methods. It was found that pyocyanin increased IL-8 release and mRNA expression in differentiated U937 cells in a concentration- and time-dependent manner. Calphostin C (Cal C), a protein kinase C (PKC) inhibitor, and pyrrolidine dithiocarbamate (PDTC) , an NF-κB inhibitor, blocked IL-8 expression in a concentration-dependent manner in pyocyanin-induced U937 cells. We concluded that pyocyanin promotes IL-8 secretion and mRNA expression in a concentration- and time-dependent manner and furthermore, that the PKC and NF-κΒ signaling pathways may be involved in the expression of IL-8 in pyocyanin-infected PMA-differentiated U937 cells.