Indirubin-3'-monoxime exhibits potent antiviral and anti-inflammatory effects against human adenoviruses in vitro and in vivo.

Human adenovirus (HAdV) infection is a major cause of respiratory disease, yet no antiviral drugs have been approved for its treatment. Herein, we evaluated the antiviral and anti-inflammatory effects of cyclin-dependent protein kinase (CDK) inhibitor indirubin-3'-monoxime (IM) against HAdV infection in cells and a transgenic mouse model. After evaluating its cytotoxicity, cytopathic effect reduction, antiviral replication kinetics, and viral yield reduction assays were performed to assess the anti-HAdV activity of IM. Quantitative real-time polymerase chain reaction (qPCR), quantitative reverse transcription PCR (qRT-PCR), and western blotting were used to assess the effects of IM on HAdV DNA replication, transcription, and protein expression, respectively. IM significantly inhibited HAdV DNA replication as well as E1A and Hexon transcription, in addition to significantly suppressing the phosphorylation of the RNA polymerase II C-terminal domain (CTD). IM mitigated body weight loss, reduced viral burden, and lung injury, decreasing cytokine and chemokine secretion to a greater extent than cidofovir. Altogether, IM inhibits HAdV replication by downregulating CTD phosphorylation to suppress viral infection and corresponding innate immune reactions as a promising therapeutic agent.

Comparative Study of the Impact of Metformin Versus Insulin on Adverse Pregnancy Outcomes in Women Diagnosed with Gestational Diabetes Mellitus: A Meta-Analysis.

Objective: This systematic comparative analysis aimed to assess the efficacy of metformin (MET) versus insulin (INS) in the treatment of gestational diabetes mellitus (GDM), providing valuable insights for future GDM management strategies. Methods: We conducted a comprehensive search of clinical studies related to MET and INS interventions in GDM through online literature databases, applying predefined inclusion and exclusion criteria. The quality of the included studies was rigorously evaluated. Data on fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), pregnancy weight gain (PWG), premature delivery rate (PDR), and neonatal outcomes among GDM patients were extracted and analyzed using Review Manager 5.3 software. Results: We identified eleven high-quality studies comprising 8679 participants following careful screening and assessment. Our meta-analysis revealed a significant reduction in the incidence of excessive PWG and neonatal hypoglycemia in the MET treatment group (research group) compared to the INS treatment group (control group) (P < .05). Conclusions: Our findings support the effectiveness and safety of MET in achieving optimal blood glucose control in GDM. These results suggest the potential for broader clinical adoption of MET in GDM management.

Comparisons of lymphocytes profiles and inflammatory cytokines levels in blood of patients with differed severity of infection by human adenovirus type 7.

BACKGROUND: Human adenovirus (HAdV) infection outbreak causes community-acquired pneumonia. Cellular immune dysfunction and hypercytokinemia play important roles in the pathogenesis of adenovirus respiratory infection. Some soluble factors in peripheral blood can assist in judging the virus-induced disease severity. The expression levels of inflammatory cytokines differ among patients with different disease severity. However, whether and how HAdV-7 infection influences the composition of blood immune cells and serum cytokine levels in patients at different disease stages, as well as the diagnosis values of these parameters, have rarely been intensively studied. We aimed to investigate lymphocytes profiles and cytokines levels in blood of patients at different disease stages upon human adenovirus type 7 (HAdV-7) infections, and explored the diagnosis values of the investigated parameters. METHODS: Patients from two outbreaks of HAdV-7 in military of China were categorized into upper respiratory infection (URI) group, common pneumonia (CP) group and severe pneumonia (SP) group according to disease severity. Peripheral blood samples were subjected to routine laboratory tests, while flow cytometry and ELISA were used to measure the lymphocyte subsets and cytokines in blood, respectively. The receiver operating characteristic (ROC) curves were performed to examine the diagnostic of these blood parameters. RESULTS: Signs of imbalanced lymphocytes composition and hypercytokinemia were observed in HAdV-7-infected patients. The percentages of CD3+ T cells and NK cells were significantly decreased along with the aggravation of the disease, particularly for NK cells and CD4+ T cells. The neutrophil to lymphocyte ratio (NLR) increased significantly in patients with more severe disease. In addition, the levels of serum CXCL10, IL-2 and TNF-α were positively correlated with disease severity, while reduced levels of IFN-γ and IL-10 were found in SP patients. Furthermore, analysis of ROC showed that multiple parameters including the percentage of blood CD3+ cells and serum CXCL10 level could predict the progression of HAdV-7 infection. CONCLUSION: Imbalance of immune state with hypercytokinemia occurred during HAdV-7 infection. The percentages of blood immune cells such as CD3+ T cells and the levels of serum cytokines such as CXCL10 showed potential diagnosis values in HAdV-7 infection.

Rare delayed cardiac tamponade in a pig after cardiac surgery.

OBJECTIVE: Delayed cardiac tamponade, a life-threatening complication of pericardial effusion in humans, has rarely been described in large animal models. We report here a pig with cardiac tamponade that developed 29 days after cardiac surgery. STUDY DESIGN: Case report. ANIMALS: One 45-kg domestic pig. METHODS: Open-chest surgery was performed on a pig to induce chronic heart failure. At 15 days after surgery, the pig's breathing appeared laboured; induced heart failure was considered the cause. Routine heart failure medications were administered. RESULTS: On day 28, the pig's status deteriorated. On day 29, echocardiography performed just before the pig's death showed a large pericardial effusion, mainly in the lateral and anterior walls of the right heart, with several fibre exudation bands. The right heart was severely compressed with an extremely small right ventricle. An emergency sternotomy was unsuccessful. Pathologic examination showed a severely thickened, fibrous pericardium. The pericardial sac was distended (up to 4.5 cm) and was full of dark brown, soft, friable material. Epicardial haemorrhage with a fresh, organised thrombus was noted in the pericardium. CONCLUSION: Delayed tamponade occurring at least 15 days after open-chest surgery is easy to misdiagnose or overlook in large animal models where attention is often focused on primary pathological model changes. To decrease mortality in animal models, researchers should be aware of potential complications and use the same level of follow-up monitoring of large animals as in clinical care.

[Pollution Characterization, Source Identification, and Health Risks of Atmospheric Particle-Bound Heavy Metals in PM2.5 in Zhengzhou City: Based on High-resolution Data].

In order to study the pollution characteristics and sources of heavy metals in urban atmospheric PM2.5, 21 elements in atmospheric PM2.5 in Zhengzhou City were detected using an online metal analyzer during July and October 2017 and January and April 2018, and the changes in heavy metal concentrations were analyzed. Heavy metals were traced by enrichment factors, principal component analysis, and potential source function. The US EPA risk assessment model was used to assess their health risks. The results showed that:the concentrations of K, Zn, Mn, Pb, Cu, As, Cr, and Se increased with the increase in pollution level. The results of enrichment factors and principal component analysis showed that the main sources of heavy metals were crust, mixed combustion, industry, and motor vehicles. The characteristic radar charts showed that the pollution dominated by crustal sources mainly occurred in spring and winter, whereas the pollution dominated by mixed combustion sources mainly occurred in winter. Pb, As, and Ni were greatly affected by the transport of a fen nutrient-laden plain, Beijing-Tianjin-Hebei, and southern Henan, whereas Cd was greatly affected by the northwest region of the sampling site. As presented a significant carcinogenic risk in both adults and children, whereas Pb and Sb presented a significant non-carcinogenic risk in children.

How to Expand and Fill the Self in Organizations: The Role of Interpersonal Processes in the Employee Organizational Identity Construction.

In the era of Volatility, Uncertainty, Complexity, and Ambiguity (VUCA), the fluidity of organizations and the variability of individual work gradually replace the traditional stability and continuity. The question of how to connect employees and organizations has long intrigued researchers and practitioners. Employee organizational identity is the stable force that binds employees to organizations. Drawing on social identity theory, we argue the role of interpersonal processes in the employee organizational identity construction. We suggest that an employee's relationship-building behaviors can promote employee organizational identity through the connected self. The indirect effect is stronger for employees who make more social comparisons because they are more sensitive to social influence. We collected data through questionnaires of 333 employees using a two-wave research design in China. The results indicate that an employee's relationship-building behaviors enhance employee organizational identity. The connected self fully mediates the positive relationship between relationship-building and employee organizational identity. The outcomes also show that the positive effect of relationship-building toward connected self is intensified, when an employee engages in more social comparisons. The findings imply that interpersonal processes play an important role in the employee organizational identity construction. Then, the theoretical and practical implications are discussed.

Atherogenic L5 LDL induces cardiomyocyte apoptosis and inhibits KATP channels through CaMKII activation.

BACKGROUND: Cardiac Ca2+/calmodulin-dependent protein kinase II (CaMKII) activation plays a critical role in cardiomyocyte (CM) apoptosis and arrhythmia. Functional ATP-sensitive potassium (KATP) channels are essential for cardiac protection during ischemia. In cultured CMs, L5 low-density lipoprotein (LDL) induces apoptosis and QTc prolongation. L5 is a highly electronegative and atherogenic aberrant form of LDL, and its levels are significantly higher in patients with cardiovascular-related diseases. Here, the role of L5 in cardiac injury was studied by evaluating the effects of L5 on CaMKII activity and KATP channel physiology in CMs. METHODS: Cultured neonatal rat CMs (NRCMs) were treated with a moderate concentration (ie, 7.5 µg/mL) of L5 or L1 (the least electronegative LDL subfraction). NRCMs were examined for apoptosis and viability, CaMKII activity, and the expression of phosphorylated CaMKIIδ and NOX2/gp91phox. The function of KATP and action potentials (APs) was analyzed by using the patch-clamp technique. RESULTS: In NRCMs, L5 but not L1 significantly induced cell apoptosis and reduced cell viability. Furthermore, L5 decreased Kir6.2 expression by more than 50%. Patch-clamp analysis showed that L5 reduced the KATP current (IKATP) density induced by pinacidil, a KATP opener. The partial recovery of the inward potassium current during pinacidil washout was susceptible to subsequent inhibition by the IKATP blocker glibenclamide. Suppression of IKATP by L5 significantly prolonged the AP duration. L5 also significantly increased the activity of CaMKII, the phosphorylation of CaMKIIδ, and the expression of NOX2/gp91phox. L5-induced apoptosis was prevented by the addition of the CaMKII inhibitor KN93 and the reactive oxygen species scavenger Mn (III)TBAP. CONCLUSIONS: L5 but not L1 induces CM damage through the activation of the CaMKII pathway and increases arrhythmogenicity in CMs by modulating the AP duration. These results help to explain the harmful effects of L5 in cardiovascular-related disease.

Serum Inflammatory Markers in Patients with Adenovirus Respiratory Infection.

BACKGROUND The aim of this study was to characterize adenovirus-associated acute respiratory infection (ARI) and observe correlations between inflammatory markers and severity of human adenovirus type 7 (HAdV-7) infection, and to evaluate the potential of inflammatory markers to predict progression from upper-respiratory infection (URI) to adenovirus pneumonia (AdP). MATERIAL AND METHODS A total of 81 patients with adenovirus-associated ARI and confirmed HAdV-7 infection were enrolled. Cases were classified according to severity, as AdP and URI. Demographic and clinical data were collected retrospectively. Clinical features and serum inflammatory markers were evaluated and compared according to the severity of adenoviral infection. RESULTS We observed high-grade fever and strong inflammatory response in patients with HAdV-7-associated ARI. Procalcitonin (PCT), interleukin 6 (IL-6), and C-reactive protein concentrations were higher in patients with AdP than in those with URI. The mean erythrocyte sedimentation rate (ESR) was significantly higher in patients with AdP (p=0.008). Reduced serum prealbumin levels were observed in patients with HAdV-7 infection. In the analysis of URI to AdP prediction ability, areas under the curve (AUCs) for all inflammatory markers were <0.9. We found that 35.9% of pneumonia had ≥2 lobars of lung infiltrate and bilateral lung infiltrate, and 20% of patients with SP had pleural effusion and atelectasis. CONCLUSIONS IL-6 and ESR were associated with the severity of HAdV-7 respiratory infection. No inflammatory marker in our study predicted URI-to-AdP progression accurately. Lung infiltration and consolidation are common in HRCT in AdP. Multiple- or single-lobar/segment consolidation was most common in SP. SP progressed very quickly after onset.

Asymptomatic pulmonary tuberculosis mimicking lung cancer on imaging: A retrospective study.

Asymptomatic pulmonary tuberculosis (PTB) mimicking lung cancer is rare and has been documented in few studies. Accurately diagnosing this atypical disease remains an enormous challenge for clinicians. The aim of the present study was to characterize asymptomatic patients with PTB who were initially diagnosed with lung cancer according to their chest computer tomography (CT) or whole-body 18F-fludeoxyglucose-positron emission tomography-computer tomography (PET-CT) presentations. The clinical characteristics and radiographic features of patients with PTB were analyzed and compared to those of patients with lung cancer. In patients with PTB, all lesions exhibited suspected malignant signs on chest CT and the maximum standard uptake value (SUVmax) of PET-CT imaging was between 2.65 and 10.9. Compared with lung cancer, the factors associated with PTB included an age <60 years (82% vs. 46%, P=0.03), being male (77% vs. 51%, P=0.025), the presence of diabetes (55% vs. 16%, P<0.01), spiculated margins (82% vs. 44%, P=0.002) and a lower SUVmax (P=0.036). The optimal cut-off level was SUVmax 8.45 for discriminating between PTB and lung cancer. At this point, the sensitivity and specificity were 63.0 and 88.9%, respectively. The results of the current study revealed methods of distinguishing between the two similar diseases. Furthermore, the results of the current study may increase awareness that although imaging of lesions may resemble lung cancer, a diagnosis of PTB should be considered. Accurate diagnosis of PTB would mean that patients would be able to avoid undergoing unnecessary operations that induce a high financial burden.

A scoring system to effectively evaluate central nervous system tuberculosis in patients with military tuberculosis.

There is currently no convenient way to effectively evaluate whether a miliary tuberculosis patient is complicated with central nervous system (CNS) tuberculosis. We aimed to find such a way by analyzing the clinical data of these patients. Fifty patients with confirmed miliary tuberculosis and 31 patients with confirmed miliary tuberculosis complicated with CNS tuberculosis from 2010 to 2014 were selected. Their general conditions, clinical features and laboratory tests were analyzed. Factors that were significantly different between them were chosen to performed multivariate and univariate logistic regression analyses, and factors with significant P values were used to establish a scoring system. Eight factors, i.e., age, cough, nausea, headache, hemoglobin (HGB), serum albumin (ALB), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), were significantly different (P < 0.05). Multivariate logistic regression analysis showed that ALB was the independent risk predictor (HR = 1.29, 95% CI 1.09-1.52, P < 0.01), whereas the others were non-independent predictors except age (P < 0.05). The scoring system was based on a summation of the scores of the assigned values of the seven predictors and had an area under the curve (AUC) of 0.86 to confirm CNS tuberculosis, with a sensitivity of 81.5% and a specificity of 81.4% at a score of 0.75 and with a specificity of 95.3% at a score of 2.75. In contrast, a score below -0.75 excluded CNS tuberculosis, with a sensitivity of 88.9% and a specificity of 62.7%. The scoring system should be useful to evaluate whether a miliary tuberculosis patient is complicated with CNS tuberculosis and could help doctors avoid excessive investigation.

Early Repolarization Pattern Predicts the Increased Risk of Ventricular Arrhythmias in Patients With Acute Anterior ST-Segment Elevation Myocardial Infarction　- A Propensity Analysis.

BACKGROUND: The association between the early repolarization pattern (ERP) and ventricular arrhythmias in patients with ST-segment elevation myocardial infarction (STEMI) remains uncertain. We hypothesized that ERP predicts the risk of sustained ventricular tachycardia (VT)/ventricular fibrillation (VF) during the acute phase of anterior STEMI.Methods and Results:We enrolled 1,460 consecutive patients with acute anterior STEMI. We identified an ERP-positive group and a 1:6 propensity-matched ERP-negative group of 183 and 471, respectively. Comparisons of sustained VT/VF, heart failure, major adverse cardiovascular events and all-cause death were based on Kaplan-Meier survival analysis and multivariable Cox proportional hazards regression with adjustment for unmatched confounding factors. In our full matching propensity score cohorts, there were 8 out of 28 variables not matching between the 2 groups. The Kaplan-Meier curves showed ERP increased the risk of sustained VT/VF in 30 days (log-rank test P=0.00065). Adjusted for baseline unmatched confounding risk, the Cox hazards regression analysis showed sustained VT/VF was associated with the present of ERP (hazard ratio=2.915, 95% CI: 1.520-5.588, P=0.001). CONCLUSIONS: In a propensity score-adjusted cohort the presence of ERP had a multivariable-adjusted association with increased risk of sustained VT/VF in patients with anterior STEMI in the early 30 days.

CXCL10/IP-10 Neutralization Can Ameliorate Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome in Rats.

The role of C-X-C motif chemokine 10 (CXCL10), a pro-inflammatory factor, in the development of acute respiratory distress syndrome (ARDS) remains unclear. In this study, we explored the role of CXCL10 and the effect of CXCL10 neutralization in lipopolysaccharide (LPS)-induced ARDS in rats. The expression of CXCL10 and its receptor chemokine receptor 3(CXCR3) increased after LPS induction. Moreover, neutralization of CXCL10 ameliorated the severity of ARDS by reducing pulmonary edema, inhibiting the release of inflammatory mediators (IFN-γ, IL-6 and ICAM-1) and limiting inflammatory cells (neutrophils, macrophages, CD8+ T cells) influx into the lung, with a reduction in CXCR3 expression in neutrophils and macrophages. Therefore, CXCL10 could be a potential therapeutic target in LPS-induced ARDS.

The Effect of Substrate Stiffness on Cardiomyocyte Action Potentials.

The stiffness of myocardial tissue changes significantly at birth and during neonatal development, concurrent with significant changes in contractile and electrical maturation of cardiomyocytes. Previous studies by our group have shown that cardiomyocytes generate maximum contractile force when cultured on a substrate with a stiffness approximating native cardiac tissue. However, effects of substrate stiffness on the electrophysiology and ion currents in cardiomyocytes have not been fully characterized. In this study, neonatal rat ventricular myocytes were cultured on the surface of flat polyacrylamide hydrogels with elastic moduli ranging from 1 to 25 kPa. Using whole-cell patch clamping, action potentials and L-type calcium currents were recorded. Cardiomyocytes cultured on hydrogels with a 9 kPa elastic modulus, similar to that of native myocardium, had the longest action potential duration. Additionally, the voltage at maximum calcium flux significantly decreased in cardiomyocytes on hydrogels with an elastic modulus higher than 9 kPa, and the mean inactivation voltage decreased with increasing stiffness. Interestingly, the expression of the L-type calcium channel subunit α gene and channel localization did not change with stiffness. Substrate stiffness significantly affects action potential length and calcium flux in cultured neonatal rat cardiomyocytes in a manner that may be unrelated to calcium channel expression. These results may explain functional differences in cardiomyocytes resulting from changes in the elastic modulus of the extracellular matrix, as observed during embryonic development, in ischemic regions of the heart after myocardial infarction, and during dilated cardiomyopathy.

Tracheobronchopathia osteochondroplastica: Case report and literature review.

Tracheobronchopathia osteochondroplastica (TPO) is a rare disorder characterized as multiple osseous or cartilaginous nodules in the submucosa of trachea and main bronchi. TPO remains an under recognized entity due to lack of awareness. Four cases of TPO are reported in this review as well as various facets of TPO description.

Neuronally released vasoactive intestinal polypeptide alters atrial electrophysiological properties and may promote atrial fibrillation.

BACKGROUND: Vagal hyperactivity promotes atrial fibrillation (AF), which has been almost exclusively attributed to acetylcholine. Vasoactive intestinal polypeptide (VIP) and acetylcholine are neurotransmitters co-released during vagal stimulation. Exogenous VIP has been shown to promote AF by shortening action potential duration (APD), increasing APD spatial heterogeneity, and causing intra-atrial conduction block. OBJECTIVE: The purpose of this study was to investigate the effects of neuronally released VIP on atrial electrophysiologic properties during vagal stimulation. METHODS: We used a specific VIP antagonist (H9935) to uncover the effects of endogenous VIP released during vagal stimulation in canine hearts. RESULTS: H9935 significantly attenuated (1) the vagally induced shortening of atrial effective refractory period and widening of atrial vulnerability window during stimulation of cervical vagosympathetic trunks (VCNS) and (2) vagal effects on APD during stimulation through fat-pad ganglion plexus (VGPS). Atropine completely abolished these vagal effects during VCNS and VGPS. In contrast, VGPS-induced slowing of local conduction velocity was completely abolished by either VIP antagonist or atropine. In pacing-induced AF during VGPS, maximal dominant frequencies and their spatial gradients were reduced significantly by H9935 and, more pronouncedly, by atropine. Furthermore, VIP release in the atria during vagal stimulation was inhibited by atropine, which may account for the concealment of VIP effects with muscarinic blockade. CONCLUSION: Neuronally released VIP contributes to vagal effects on atrial electrophysiologic properties and affects the pathophysiology of vagally induced AF. Neuronal release of VIP in the atria is inhibited by muscarinic blockade, a novel mechanism by which VIP effects are concealed by atropine during vagal stimulation.

Computed tomography for the diagnosis of solitary thin-walled cavity lung cancer.

BACKGROUND AND AIM: Lung cancer is the most commonly diagnosed neoplasm and the leading cause of cancer-related death worldwide. Despite the high incidence of lung cancer, the diagnosis of solitary thin-walled cavity lung cancer is rare. The aim of this review is to explore the potentials of computed tomography (CT) as diagnostic tool for solitary thin-walled cavity lung cancer. METHOD: The literature search was made in electronic databases including PudMed, Ovid SP, Embase, Web of Sciences, EBSCO and Wiley online by using relevant key terms. Because of the rarity of the subject, no precise exclusion or inclusion criteria were used for article selection and the outcome dissemination was decided to be more descriptive rather than quantitative. RESULTS: The detection of cavitation in lungs is frequently done utilizing chest radiographs CT scans. However, the diagnostic challenge remains the accurate detection of solitary thin-walled cavity lung cancer among the prevalence of cavitary lung lesions in multiple thoracic disorders including benign disorders, infectious disease and malignant tumors. Moreover, an accurate diagnosis of solitary thin-walled cavity lung cancer is further complicated by its subjective classification within the literature. In order to facilitate early diagnosis of this disease and circumvent the need for more invasive tests that may not be warranted, the overarching goal is to establish definitive radiological features of lung cavities that are indicative of malignancy. Herein, we describe the benefits of using CT to identify and diagnose solitary thin-walled cavity lung cancer, as well as explore the underlying mechanisms that contribute to thin-walled cavity formation in oncology patients. CONCLUSION: CT is the best modality for the noninvasive differentiation between malignant and nonmalignant cavities as it provides reliable information regarding the morphology and density of lesions. Besides, CT densitometry can efficiently detect the calcifications in lesions.

Dynamic assessment of the changing geometry of the mitral apparatus in 3D could stratify abnormalities in functional mitral regurgitation and potentially guide therapy.

INTRODUCTION: In functional mitral regurgitation (FMR), effective regurgitant orifice area (EROA) displays a dynamic pattern. The impact of dynamic changes of annulus dysfunction and leaflets tenting on phasic EROA was explored with real-time three-dimensional transesophageal echocardiography (RT3D-TEE). METHODS: RT3D-TEE was performed in 52 FMR patients and 30 controls. Mitral annulus dimensions and leaflets tenting were measured throughout systole (TomTec, Germany). Phasic EROA was measured by proximal isovelocity surface area (PISA) method. RESULTS: Mitral annulus had the minimal area and an oval shape with saddle configuration during early systole in controls, which enlarged and became round and flattened towards mid and late systole (P<0.05). In contrast, annulus in FMR was significantly larger, rounder and flatter (P<0.001), which further dilated and became more flattened at late systole (P<0.05 vs control). Leaflet tenting height in FMR decreased in mid systole and remains unchanged towards late systole. The leaflet tenting volume peaked at early and late systole with a mid-systolic trough in both FMR and controls. But tenting volume of patients with FMR was significantly larger than that of controls (all P<0.001 vs control in whole systole). Further analysis demonstrated that early tenting volume (ß value=0.053, P<0.05) was a predictor of early EROA, whereas late tenting volume (ß value=0.031, P<0.05) and late annular displacement velocity were predictors of late EROA. CONCLUSIONS: The early and late peak EROAs of FMR was primarily contributed by tenting volume at early systole and late systole respectively. These findings would be of value to consider in interventions aimed at reducing the severity of FMR.