Residual HBV DNA and pgRNA viraemia is associated with hepatocellular carcinoma in chronic hepatitis B patients on antiviral therapy

Journal of Gastroenterology - We aimed to assess whether residual hepatitis B virus (HBV) viraemia is associated with HCC development. This is a case–control study of 104 patients [52 HCC and...     

The effects of Chinese herb Angelica in focal cerebral ischemia injury in the rat

This experiment was designed to study the therapeutic mechanisms of Angelica on the focal cerebral ischemia injury of the rat. The ischemic area was determined by TTC stain. And terminal deoxynucleotidyl transferase (TDT) mediated DUTP-biotin nick end labeling (TUNEL) method was applied to detect neuronal apoptosis. The expressions of Bcl-2 and Bax proteins were observed by immunohistochemical staining methods. Results show that the treatment with angelica reduced the volume of cerebral infarction (p < 0.05), and that the number of neuronal apoptosis cells decreased significantly (p < 0.01). Also the expression level of Bax protein decreased (p < 0.01). These results suggest that Angelica can reduce the number of apoptosis cells by decreasing the expression of Bax protein. This is maybe one of the mechanisms of the therapeutic effect of Angelica on focal cerebral ischemia injury.     

Age-associated accumulation of CMV-specific CD8+ T cells expressing the inhibitory killer cell lectin-like receptor G1 (KLRG1)

Large clonal expansions of peripheral CD8+ T cells carrying receptors for single epitopes of CMV and EBV are common in the elderly and may be associated with an immune risk phenotype predicting mortality. Here we show that the frequency of CD8+ T cells expressing the inhibitory killer cell lectin-like receptor G1 (KLRG1), a marker of cells unable to undergo further clonal expansion, was markedly elevated in CD8+ T cells from old donors. Moreover, tetramer staining revealed that the elevated frequency of CMV-specific CD8+ T cells in the elderly was due to an accumulation of cells bearing this dominant negative receptor. The fraction of CMV-specific T cells able to secrete interferon-gamma after specific antigenic stimulation was significantly lower in the elderly than in the young, although the total number of functional cells was comparable. Therefore, the majority of the clonally expanded virus-specific CD8+ cells in the elderly was dysfunctional. Thus, T cell responses are altered in the aged by an accumulation of replicatively senescent dysfunctional T cells carrying receptors for persistent herpes viruses. The presence of clonal expansions of such virus-specific cells may shrink the available repertoire for other antigens and contribute to the increased incidence of infectious disease in the elderly.     

Thrombolysis in postinfarction angina

Postinfarction angina carries a poor prognosis, with a 20-70% incidence of recurrent myocardial infarction (MI) or death within the subsequent 3-6 months. The pathophysiologic mechanisms causing postinfarction angina may include thrombus, complex coronary arterial lesions that form a nidus for thrombus formation, inadequate collateral supply following acute MI, or intimal endothelial dysfunction. The role of thrombus has been established in the pathophysiology of Q-wave MI, and thrombolytic treatment of patients presenting with acute transmural MI has been shown to salvage left ventricular function and to reduce mortality. However, thrombolytic therapy for the acute MI does not reduce the incidence of recurrent ischemia or infarction, as is evident from the 18-26% incidence of recurrent ischemia reported in the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) and Thrombolysis in Myocardial Infarction (TIMI) trials. In the Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico (GISSI) study the incidence of reinfarction was documented as 4% in the streptokinase group, which was actually significantly greater than in the placebo group (2%). In a randomized placebo-controlled study of thrombolysis for postinfarction angina, 29 patients were randomized to placebo (P group, n = 17) or to thrombolytic therapy (T group, n = 12). Patient groups were similar with respect to age, location of MI, ejection fraction, severity of coronary artery disease, and antianginal therapy. Patients underwent coronary angiography 6 +/- 1 days postinfarction. Filling defects consistent with intracoronary thrombus was seen in 11 of 12 T group patients and in 11 of 17 P group patients prior to treatment. Lysis occurred in 7 of 11 T patients and 1 of 11 P (p less than 0.02). Holter-detected silent ischemia was compared pre- and posttherapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Esophageal chest pain

The unequivocal diagnosis of esophageal chest pain requires the demonstration of simultaneous manometric changes and chest pain. Numerous provocative agents have been used to enhance the diagnostic value of esophageal manometry. Our aims were to: evaluate consecutively a large group of patients with proven noncardiac chest pain and normal baseline manometric studies, using edrophonium chloride, 10 mg, and determine the value of provocative testing in clinical practice. One hundred twenty patients with normal standard baseline esophageal manometries were studied using blinded testing with edrophonium chloride and followed clinically by questionnaire. A positive response of both chest pain and manometric changes was observed in 34%, a negative response in 49%, and an indeterminate response in 17% of patients. Baseline manometric features, including high-amplitude contractions, did not predict the response to edrophonium chloride. Following edrophonium chloride administration, the change in amplitude, duration, and number of repetitive contractions from baseline was significantly greater in positive responders. Edrophonium decreased the velocity of propagated contractions in positive responders (P less than 0.05), but not in nonresponders. Response to edrophonium chloride could not be predicted by patient age, sex, or clinical symptomatology. Seventy percent of patients in both groups had symptoms indistinguishable from ischemic heart disease. After making a specific diagnosis of esophageal chest pain, patients showed a marked clinical improvement, with a significant decrease in physical limitation, emergency room visits, hospital and CCU admissions, and in further cardiac testing. We conclude that provocative testing with edrophonium chloride will make it possible to definitively implicate the esophagus in over 30% of patients with normal baseline manometric findings and noncardiac chest pain.     

Separating stimulus‐driven and response‐related LRP components with Residue Iteration Decomposition (RIDE)

When the lateralized readiness potential (LRP) is recorded in stimulus–response compatibility (SRC) tasks, two processes may overlap in the LRP, stimulus‐driven response priming and activation based on response selection rules. These overlapping processes are hard to disentangle with standard analytical tools. Here, we show that Residue Iteration Decomposition (RIDE), based on latency variability, separates the overlapping LRP components from a Simon task into stimulus‐driven and response‐related components. SRC affected LRP amplitudes only in the stimulus‐driven component, whereas LRP onsets were affected only in the response‐locked component. Importantly, the compatibility effect in reaction times was more similar to the effect in the onsets of the RIDE‐derived response‐locked LRP component than in the unseparated LRP. Thus, RIDE‐separated LRP components are devoid of distortions inherent to standard LRPs.     

Epidemiological,Clinical, Radiological Characteristics and Outcomes of Medical Staff with COVID-19 in Wuhan,China: Analysis of 101 Cases

Objectives: As of 11 Feb 2020, a total of 1,716 medical staff infected with laboratory-confirmed the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) in China had been reported. The predominant cause of the infection among medical staff remains unclear. We sought to explore the epidemiological, clinical characteristics and prognosis of infected medical staff.Methods: Medical staff who infected with SARS-Cov-2 and admitted to Union Hospital, Wuhan between 16 Jan to 25 Feb, 2020 were included in this single-centered, retrospective study. Data were compared by occupation and analyzed with the Kaplan-Meier and Cox regression methods.Results: A total of 101 medical staff (32 males and 69 females; median age: 33) were included in this study and 74.3% were nurses. A small proportion of the cohort had contact with specimens (3%) as well as patients infected with SARS-Cov-2 in fever clinics (15%) and isolation wards (3%). 80% of medical staff showed abnormal IL-6 levels and 33% had lymphocytopenia. Chest CT mainly manifested as bilateral (62%), septal/subpleural (77%) and groundglass opacities (48%). The major differences between doctors and nurses manifested in laboratory indicators. As of the last observed date, no patient was transferred to intensive care unit or died. Fever (HR=0.57; 95% CI 0.36-0.90) and IL-6 levels greater than 2.9 pg/ml (HR=0.50; 95% CI 0.30-0.86) were unfavorable factors for discharge.Conclusions: Our findings suggested that the infection of medical staff mainly occurred at the early stages of SARS-CoV-2 epidemic in Wuhan, and only a small proportion of infection had an exact mode. Meanwhile, medical staff infected with COVID-19 have relatively milder symptoms and favorable clinical course than ordinary patients, which may be partly due to their medical expertise, younger age and less underlying diseases. The potential risk factors of fever and IL-6 levels greater than 2.9 pg/ml could help to identify medical staff with poor prognosis at an early stage.     

DNA adsorption on nanoscale zeolitic imidazolate framework-8 enabling rational design of a DNA-based nanoprobe for gene detection and regulation in living cells

DNA functionalized nanomaterials have attracted tremendous attention for bioanalytical applications. Owing to exceptional fluorescence quenching ability, most DNA-based nanoprobes were designed with turn-on signals for target gene detection, while only a few of them could simultaneously achieve gene detection and regulation in one system. In this study, we explored the use of nanoscale zeolitic imidazolate framework-8 (ZIF-8) as a building block to construct a DNA-based nanoprobe. We found ZIF-8 could stably adsorb DNA to resist the dissociation by various biological ligands, enabling potential biological applications. However, ZIF-8 was not a nano-quencher to turn off the fluorophore labeling on the adsorbed DNA. We therefore designed a DNAzyme embedded molecular beacon (DMB) to functionalize ZIF-8. After endocytosis, ZIF-8 was disintegrated to release DMB for target mRNA detection, and the co-released Zn²⁺ acted as an effective cofactor to activate the embedded DNAzyme for mRNA regulation. This study provides a versatile nano-platform to realize multiple functions inside cells by using functional nucleic acids, which holds great promise for theranostic applications.

Boosting DNA-based nanotheranostics for gene detection and regulation by ZIF-8.