Gensheng Zhang

Neonatal vaccination with Bacillus Calmette-Guérin elicits long-term protection in mouse-allergic responses.

Background:  Mycobacterium bovis Bacillus Calmette‐Guérin (BCG) vaccination has been shown to inhibit allergic airway inflammation in animal models, associated with the regulation of allergen‐specific T‐cell immunity. However, little is known about whether neonatal BCG treatment could inhibit allergic inflammation by regulating allergen‐specific T‐cell response in aged mice. This study was aimed to investigate the impact of neonatal BCG treatment on allergic asthma and possible mechanism(s) underlying the action of BCG in different ages of mice.

Protein tyrosine phosphatase SHP2 regulates TGF-β1 production in airway epithelia and asthmatic airway remodeling in mice

Transforming growth factor (TGF)‐β1 produced in airway epithelia has been suggested as a contributor to the airway remodeling observed in asthma patients. The protein tyrosine phosphatase SHP2 is a demonstrable modulator of TGF‐β1 production and thus a potential regulator of airway remodeling.

Inhibition of allergen-induced airway remodeling by neonatal bacillus Calmette-Guerin vaccination is associated with interferon-gamma–producing T cells but not regulatory T cells in mice

BACKGROUND Epidemiological assessments of patients and studies using animal models show that exposure to Mycobacterium bovis bacillus Calmette-Guerin (BCG) vaccine in early life prevents asthma development. However, little is known about the potential of neonatal BCG vaccination in preventing the development of airway remodeling of asthma. OBJECTIVE To investigate the effects of multiple BCG vaccinations of neonates on the airway remodeling in mice and the accompanied pulmonary T cell responses. METHODS BALB/c neonates were vaccinated with BCG 3 times. At 5 and 7 weeks of age, the mice were sensitized and then challenged with aerosolized ovalbumin (OVA) 3 times per week for 8 successive weeks. The extent of airway remodeling and induced pulmonary T cell responses were characterized. RESULTS Multiple BCG vaccinations of neonates reduced OVA-induced remodeling events, including levels of peribronchial α-smooth muscle actin, peribronchial fibrosis, and airway epithelial mucin accumulation. The BCG vaccinations also decreased peribronchial cells expression of transforming growth factor beta 1 (TGF-β1). In contrast, BCG vaccinations increased the frequency of interferon-gamma (IFN-γ)-producing T cells in the lung and IFN-γ level in BALF, with no effects on pulmonary regulatory T cells and IL-17-producing T cells. CONCLUSIONS Our data suggest that multiple BCG vaccinations of neonates reduced metrics characteristic of allergen-induced airway remodeling. More importantly, this decrease was not associated with an increased number of pulmonary regulatory T cells but instead correlated with an increase of IFN-γ-producing T cells.

Distant lymph nodes serve as pools of Th1 cells induced by neonatal BCG vaccination for the prevention of asthma in mice.

Neonatal Bacillus Calmette–Guérin (BCG) vaccination induces vigorous T‐helper type 1 (Th1) responses and inhibits allergy‐related airway dysfunction, but the exact mechanisms remain unclear. The objective of this study was to address where the Th1 cells induced by neonatal BCG vaccination are generated and stored, and how they are recruited into the inflamed airway for the prevention of allergen‐induced airway inflammation.

The Antidiabetic Agent Glibenclamide Protects Airway Hyperresponsiveness and Inflammation in Mice

Glibenclamide has a newly discovered role in inflammation regulation besides its antidiabetic effect. As an inhibitor of ATP-sensitive potassium (KATP) channel, glibenclamide antagonizes the relaxation of the tracheal smooth muscle. This indicates that glibenclamide might attenuate airway inflammation while aggravate airway hyperresponsiveness (AHR) in asthmatics. Clinically, many diabetics with asthma are prescribed with glibenclamide to control blood glucose. However, whether glibenclamide could exert any effects on asthmatic inflammation remains unknown. Using an ovalbumin (OVA)-induced mouse model of asthma, we evaluated the effects of glibenclamide on the AHR and inflammation. Interestingly, glibenclamide reduced all the cardinal features of asthma in OVA-challenged mice, including AHR, airway inflammation, and T-helper type 2 (Th2) cytokines. Glibenclamide also downregulated OVA-induced expressions of vascular cell adhesion molecule 1 (VCAM-1) and phosphorylated signal transducer and activator of transcription 6 (p-STAT6) in the lung. In addition, increased sulfonylurea receptor 1 (SUR1) expression in the lung was observed after the OVA challenge. These findings suggest that the classic sulfonylurea glibenclamide plays an important protective role in the development of asthma, which not only provides the evidence for the safety of prescribed glibenclamide in diabetics combined with asthma but also indicates a possible new therapeutic for asthma via targeting glibenclamide-related pathways.

Multiple synchronous primary malignancies induced by benzene exposure: a case report.

BackgroundChronic exposure to high concentrations of benzene is usually associated with the development of haematological diseases. However, solid tumors induced by benzene exposure are less frequent.Case presentationWe present an unusual case of triple synchronous primary malignancies most likely induced by occupational benzene exposure in a male patient. This spray painter was diagnosed as chronic aplastic anemia in his 21 years old after exposing to high concentration of benzene for three years. Then he was treated with glucocorticoid for four years. 40 years later, this patient developed three synchronous primary neoplasms with three different histologies including a basaloid squamous cell carcinoma of the esophagus, primary hepatocellular carcinoma, and well-differentiated squamous cell carcinoma of the gum.ConclusionThis case reminds us that the occurrence of solid tumors should be monitored in workers with occupational history linked with a high concentration exposure to benzene, though its rarely happened.

A Protective Role of Glibenclamide in Inflammation-Associated Injury

Glibenclamide is the most widely used sulfonylurea drug for the treatment of type 2 diabetes mellitus (DM). Recent studies have suggested that glibenclamide reduced adverse neuroinflammation and improved behavioral outcomes following central nervous system (CNS) injury. We reviewed glibenclamides anti-inflammatory effects: abundant evidences have shown that glibenclamide exerted an anti-inflammatory effect in respiratory, digestive, urological, cardiological, and CNS diseases, as well as in ischemia-reperfusion injury. Glibenclamide might block KATP channel, Sur1-Trpm4 channel, and NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome activation, decrease the production of proinflammatory mediators (TNF-α, IL-1β, and reactive oxygen species), and suppress the accumulation of inflammatory cells. Glibenclamides anti-inflammation warrants further investigation.

The Role of Macrophages in the Pathogenesis of ALI/ARDS

Despite development in the understanding of the pathogenesis of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), the underlying mechanism still needs to be elucidated. Apart from leukocytes and endothelial cells, macrophages are also essential for the process of the inflammatory response in ALI/ARDS. Notably, macrophages play a dual role of proinflammation and anti-inflammation based on the microenvironment in different pathological stages. In the acute phase of ALI/ARDS, resident alveolar macrophages, typically expressing the alternatively activated phenotype (M2), shift into the classically activated phenotype (M1) and release various potent proinflammatory mediators. In the later phase, the M1 phenotype of activated resident and recruited macrophages shifts back to the M2 phenotype for eliminating apoptotic cells and participating in fibrosis. In this review, we summarize the main subsets of macrophages and the associated signaling pathways in three different pathological phases of ALI/ARDS. According to the current literature, regulating the function of macrophages and monocytes might be a promising therapeutic strategy against ALI/ARDS.

Characteristics of clinical and environmental vanM-carrying vancomycin-resistant enterococci isolates from an infected patient

vanM, an uncommon glycopeptide resistance gene, was first identified in an Enterococcus faecium isolate (Efm-HS0661) from Shanghai, China, in 2006 and has been predominant in this city since 2011. A vanM-carrying E. faecium was isolated from the bloodstream of a patient in an intensive care unit (ICU) in Hangzhou, China, in 2014. Further surveillance screening of a rectal swab and environmental surfaces of the patient yielded a large number of vanM-positive E. faecium. These isolates (including 1 from the bloodstream, 1 from the rectal swab and 43 representative isolates from environmental samples) were classified into four pulsed-field gel electrophoresis (PFGE) patterns and two sequence types (ST78 and ST564). PCR amplification and sequence analysis indicated that the genetic structure surrounding the vanM gene of these isolates was similar to that of the original vanM-carrying isolate Efm-HS0661. This study highlights the emergence of infections and environmental contamination caused by vanM-carrying E. faecium in an ICU of another Chinese city outside of Shanghai.

Efficacy of intravenous plus intrathecal/intracerebral ventricle injection of polymyxin B for post-neurosurgical intracranial infections due to MDR/XDR Acinectobacter baumannii: a retrospective cohort study

BackgroundPost-neurosurgical intracranial infections caused by multidrug-resistant or extensively drug-resistant Acinetobacter baumannii are difficult to treat and associated with high mortality. In this study, we analyzed the therapeutic efficacy of intravenous combined with intrathecal/intracerebral ventricle injection of polymyxin B for this type of intracranial infection.MethodsThis retrospective study was conducted from January 2013 to September 2017 at the Second Affiliated Hospital, Zhejiang University School of Medicine (Hangzhou,China) and included 61 cases for which cerebrospinal fluid (CSF) cultures were positive for multidrug-resistant or extensively drug-resistant A. baumannii after a neurosurgical operation. Patients treated with intravenous and intrathecal/intracerebral ventricle injection of polymyxin B were assigned to the intrathecal/intracerebral group, and patients treated with other antibiotics without intrathecal/intracerebral injection were assigned to the intravenous group. Data for general information, treatment history, and the results of routine tests and biochemistry indicators in CSF, clinical efficiency, microbiological clearance rate, and the 28-day mortality were collected and analyzed.ResultsThe rate of multidrug-resistant or extensively drug-resistant A. baumannii infection among patients who experienced an intracranial infection after a neurosurgical operation was 33.64% in our hospital. The isolated A. baumannii were resistant to various antibiotics, and most seriously to carbapenems (100.00% resistance rate to imipenem and meropenem), cephalosporins (resistance rates of 98.38% to cefazolin, 100.00% to ceftazidime, 100.00% to cefatriaxone, and 98.39% to cefepime). However, the isolated A. baumannii were completely sensitive to polymyxin B (sensitivity rate of 100.00%), followed by tigecycline (60.66%) and amikacin (49.18%). No significant differences in basic clinical data were observed between the two groups. Compared with the intravenous group, the intrathecal/intracerebral group had a significantly lower 28-day mortality (55.26% vs. 8.70%, P = 0.01) and higher rates of clinical efficacy and microbiological clearance (95.65% vs. 23.68%, P < 0.001; 91.30% vs. 18.42%, P < 0.001, respectively).ConclusionsIntravenous plus intrathecal/intracerebral ventricle injection of polymyxin B is an effective regimen for treating intracranial infections caused by multidrug-resistant or extensively drug-resistant A. baumannii.