No abstract

No abstract

Nerve growth factor (NGF) is critical in the pathogenesis of allergic airway inflammation in vivo and induces proliferation of airway smooth muscle cells and matrix metalloproteinase-9 (MMP-9) expression in vitro. However, the effects of NGF on chronic pulmonary diseases of allergic origin remain unknown. To investigate the effects of NGF on lung inflammation and airway remodeling, 32 Wistar rats were randomly divided into four groups: control, NGF, ovalbumin (OVA) and anti-rat-β-NGF antibody (anti-NGF). Aerosolized OVA was administered to the rats in the NGF, OVA and anti-NGF groups to generate the asthmatic rat model, and NGF or anti-NGF was administered 3 h prior to OVA inhalation every two days. On day 70, bronchial responsiveness tests, bronchoalveolar lavage (BAL) and cell counting were conducted. The levels of serum OVA-specific immunoglobulin E (IgE) and of T-helper cell type-2 (Th2) cytokines [interleukin (IL)-4 and IL-13] in the BAL fluid were measured by enzyme-linked immunosorbent assay. The expression levels of NGF protein and MMP-9 mRNA, and the activity of MMP-9 in the lungs were detected by western blot analysis, quantitative polymerase chain reaction and gelatin zymography analysis, respectively. Our results showed that NGF significantly increased eosinophilic airway inflammation, persistent airway hyperresponsiveness (AHR), the serum levels of OVA-specific IgE and the levels of Th2 cytokines in the BAL fluid, and also increased the expression levels and activity of MMP-9. However, anti-NGF treatment significantly inhibited eosinophilic airway inflammation, persistent AHR and airway remodeling. The results showed that NGF may have exacerbated the development of airway inflammation, AHR and airway remodeling through a Th2 pathway and by increasing the level of MMP-9 expression. Therefore, anti-NGF is potentially beneficial for preventing and treating patients with asthma.

Abstract:The collapse of abandoned room-and-pillar mines is often violent and unpredictable. Safety concerns often resulted in mine closures with no post-mining stability evaluations. As a result, large amounts of land resources over room-and-pillar mines are wasted. This paper attempts to establish an understanding of the long-term stability issues of goafs (abandoned mines). Considering progressive pillar failures and the effect of single pillar failure on surrounding pillars, this paper proposes a pillar peeling model to evaluate the long-term stability of coal mines and the associated criteria for evaluating the long-term stability of room-and-pillar mines. The validity of the peeling model was verified by numerical simulation, and field data from 500 pillar cases from China, South Africa, and India. It is found that the damage level of pillar peeling is affected by the peel angle and pillar height and is controlled by the pillar width-height ratio.

Abstract:Partial extraction methods such as underground strip pillar mining or room-and-pillar mining are widely adopted techniques to control ground subsidence. However, pillar failure in partial extraction mines may introduce violent secondary ground collapses. The stability of partial extraction mines dictates the safety of ground surface structures and the environmental health state of the surrounding mining areas. To reuse mining subsidence lands, it is necessary to evaluate the stability of the land through mine subsidence assessments. This paper summarizes current pillar stability assessment methods and their limitations, and the rock mechanics associated with the stability of abandoned mines. The effects of multiple factors that affect mine stability are discussed in detail; special attention has been extended to discuss the weathering effects associated with infused water and spontaneous combustion, as these are some key reasons for pillar strength degradation in abandoned mines. The mechanism of mine collapse and the corresponding post-mining disasters are also summarized. Finally, suggestions and strategies to improve current mine stability assessment methods are proposed based on the perspective of subsidence control.

Airway remodeling and airway hyper-responsiveness are prominent features of asthma. Neurogenic inflammation participates in the development of asthma. Neurokinin substance P acts by binding to neurokinin-1 receptor (NK-1R). Airway smooth muscle cells (ASMC) are important effector cells in asthma. Increases in ASMC proliferation, migration, and cytoplasmic Ca2+ concentration are critical to airway remodeling and hyper-responsiveness. The effects of substance P on ASMC were investigated in Wistar rats challenged with a previously described asthmatic rat model. To exclude possible influences from other factors, the role of substance P was also investigated in primary cultured rat ASMC. Substance P and WIN62577-induced changes in cytoplasmic Ca2+ concentration were observed by fluorescence microscopy, and expression of Ca2+ homeostasis-regulating genes was assessed with real-time PCR. We found that cytoplasmic Ca2+ concentration increased in normal rat ASMC treated with substance P, but decreased in asthmatic rat ASMC treated with WIN62577, an antagonist of NK-1R. Real-time PCR analysis revealed increased Serca2 mRNA expression but decreased Ip3r mRNA expression after WIN62577 treatment in asthmatic rat ASMC. Flow cytometric analysis (FCM) revealed that most asthmatic rat ASMC stayed at G1 phase after combined treatment with WIN62577 and IL-13 in vitro. Transwell analysis suggested that ASMC migration was reduced after WIN62577 treatment. Therefore, we conclude that NK-1R is related to asthma mechanisms and a NK-1R antagonist downregulates calcium concentration in asthmatic ASMC by increasing Serca2 mRNA and decreasing Ip3r mRNA expression. The NK-1R antagonist WIN62577 inhibited ASMC IL-13-induced proliferation and ASMC migration in vitro and therefore may be a new therapeutic option in asthma.

Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome (DIHS) is a rare, severe cutaneous adverse drug reaction characterized by fever, skin rashes, lymphadenopathy, leukocytosis with eosinophilia, and/or atypical lymphocytosis, and multiple visceral organ involvement. Moreover, patients with DRESS are at risk of developing autoimmune diseases including thyroiditis, diabetes mellitus (DM), and systemic lupus erythematosus (SLE), etc. several weeks or months after the initial resolution. We described a 9-month boy who was admitted to our hospital because of severe pneumonia and developed DRESS 3 weeks later. After the withdrawal of suspicious drug and administration of systemic corticosteroids, the patient's condition improved gradually. Nevertheless, hyperglycemia was detected 20 days after the initial onset of DRESS, and subsequent fulminant type 1 diabetes mellitus (F1DM) was diagnosed requiring continuous intravenous insulin infusion. After 13 months of follow-up, the blood glucose levels are now well-controlled. Literature research in PubMed for diabetes mellitus associated with DRESS showed 16 articles and 27 related case reports. Of 27 patients with DM related to DRESS, 11 were male, 16 were female. The mean age was 46 years. The duration from the onset of DRESS to the development of DM was 21 days on average. F1DM was diagnosed in 21 patients, T1DM was confirmed in 5 patients, and T2DM was only defined in 1 patient. Glutamic acid decarboxylase antibodies (GAD) were detected in 4 cases. Of 22 cases in which virus examination was carried out, evidence of virus reactivation was established in 16 cases (72.7%). Of patients with F1DM, 16 (88.9%) cases were evidenced by reactivation of herpes virus. A high frequency of HLA genotype and haplotype were found in 11 cases. DM was concomitant with acute pancreatitis in 3 patients and thyroiditis in 2 patients. No patients died from the disease. This work aims to raise awareness of long-term autoimmune sequelae in patients with DRESS.

Kawasaki disease (KD) is a systemic vasculitis that can present various manifestations in children, including neural, gastrointestinal, hepatobiliary involvement, and so on. With the development of abdominal ultrasound, complications of hydrops with or without cholestasis in KD are being recognized more frequently. However, this is rarely reported in China. Case Presentation A 6-year-old boy previously well was admitted to the hospital with a history of fever for 4 days, rash, and stiff neck for 2 days; he also complained of a diffuse abdominal pain, fatigue, and acholic stool. At admission, physical examination was significant for icterus, bilateral conjunctivitis, red cracked lips, a "strawberry tongue", tenderness, bilateral cervical lymphadenopathy, normal cardiac and respiratory patterns, abdominal dilatation and diffuse pain without guarding, and no palpable mass; on the second day of admission, he developed a desquamation around anus. The rash faded away after 2 days in hospital, and on the eighth day of hospitalization, desquamation of the fingertips was noted. Laboratory results on admission showed an elevation of inflammatory indices: a white blood cell count of 19.2 × 10 9 /L with 75% neutrophil; platelet count of 288 × 10 9 /L, which then rose to 633 × 10 9 /L on the ninth day of admission; erythrocyte sedimentation rate 60 mm/h; and C-reactive protein >90 mg/L; liver function test showed a total serum bilirubin of 164.9 µmol/L with a direction fraction of 65.9%, accompanied by an elevated alkaline phosphatase and γ-glutamly transferase. Hypoproteinmia and hyponatremia were noted, renal function was normal, and blood culture was sterile. The diagnosis of KD was made at admission. Chest X-ray showed blunted costophrenic angles; ultrasound of abdomen revealed hydrops of the gallbladder (GB) measuring 9.7 cm in longitudinal and 5.4 cm in anteroposterior diameter, with no calculi, no thickness of the walls or evidence of sludge, and a spleen enlargement and mesenteric nodes enlargement; ascites was also found (Figure 1). A differential diagnosis of hematologic malignancies disease was considered and further