Development of local anesthetic drug delivery system by administration of organo-silica nanoformulations under ultrasound stimuli: in vitro and in vivo investigations.

The development of local anesthetic (LA) system is the application of commercial drug for the pain management that indorses the reversible obstructive mechanism of neural transmission through preventing the innervation process in human peripheral nerves. Ropivacaine (RV) is one of the greatest frequently used LA s with the actions of long-lasting and low-toxicity for the post-operative pain management. In this work, we have approached novel design and development of glycosylated chitosan (GCS) encapsulated mesoporous silica nanoparticles (GCS-MONPs)-based nano-scaffold for sustainable distributions and controlled/supported arrival of stacked RV for targeting sites, which can be activated by either outer ultrasound activating to discharge the payload, foundation on-request and dependable analgesia. The structural and morphology analyses result established that prepared nano-formulations have successful molecular interactions and RV loaded spherical morphological structures. The drug release profile of developed nanostructure with ultrasound-activation has been achieved 50% of drug release in 2 h and 90% of drug release was achieved in 12 h, which displays more controlled release when compared to free RV solution. The in vitro cell compatibility analysis exhibited GCS-MONPs with RV has improved neuron cell survival rates when compared to other samples due to its porous surface and suitable biopolymer proportions. The analysis of ex vitro and in vivo pain relief analysis demonstrated treated animal models have high compatibility with GCS-MONPs@RV, which was confirmed by histomorphology. This developed MONPs based formulations with ultrasound-irradiation gives a prospective technique to clinical agony the board through on-request and dependable help with discomfort.

Clinical and Radiological Profile of Acute Fibrinous and Organizing Pneumonia: A Retrospective Study.

BACKGROUND: Acute fibrinous and organizing pneumonia (AFOP) is a unique pathological entity with intra-alveolar fibrin in the form of "fibrin balls" and organizing pneumonia. It was divided into rare idiopathic interstitial pneumonia according to the classification notified by American Thoracic Society/European Respiratory Society in 2013. As a rare pathological entity, it is still not well known and recognized by clinicians. We reviewed the clinical features of 20 patients with AFOP diagnosed in a teaching hospital. METHODS: The medical records of 20 patients with biopsy-proven diagnosis of AFOP were retrospectively reviewed. The patients' symptoms, duration of the disease, comorbidities, clinical laboratory data, pulmonary function testing, radiographic studies, and the response to treatment were extracted and analyzed. RESULTS: Fever was the most common symptom and was manifested in 90% of AFOP patients. For clinical laboratory findings, systematic inflammatory indicators, including C-reactive protein and erythrocyte sedimentation rate, were significantly higher than normal in AFOP patients. In accordance with this increased indicators, injured liver functions were common in AFOP patients. Inversely, AFOP patients had worse clinical conditions including anemia and hypoalbuminemia. For pulmonary function testing, AFOP patients showed the pattern of restrictive mixed with obstructive ventilation dysfunction. For high-resolution computerized tomography (HRCT) findings, the most common pattern for AFOP patients was lobar consolidation which was very similar to pneumonia. However, unlike pneumonia, AFOP patients responded well to glucocorticoids. CONCLUSION: Patients with AFOP manifest as acute inflammatory-like clinical laboratory parameters and lobar consolidation on HRCT, but respond well to steroid.

Solitary endobronchial papillomas with false impression of malignant transformation: report of two cases and review of the literature.

Solitary endobronchial papillomas (SEPs) are rare benign tumors of the lung, seldom transform to malignancy. This tumor had been reported occasionally manifest like carcinomas histologically. Herein we report 2 cases of SEPs; one is a squamous cell papilloma providing a false impression of interstitial micro-invasion. The other is a mixed squamous cell and glandular papilloma with massive lipid pneumonia gross appearance, and focally resembles adenocarcinoma with lepidic-like pattern on histological examination. A review of associated literatures was provided.

Multfocal micronodular pneumocyte hyperplasia in a Chinese man masquerading as miliary tuberculosis.

Multifocal Micronodular Pneumocyte Hyperplasia (MMPH) is a rare and histologically, distinctive pulmonary manifestation of tuberous sclerosis complex (TSC) characterized by numerous and extensive proliferative lesions of type II pneumocytes similar to atypical adenomatous hyperplasia (AAH) or non-mucinous adenocarcinoma in situ (AIS). We reported MMPH in a 38-year-old Chinese man with TSC masquerading for 16 months as miliary tuberculosis and discussed the differential diagnosis.

Clinicopathological features of pulmonary cryptococcosis with cryptococcal titan cells: a comparative analysis of 27 cases.

In addition to the typical size, Cryptococcus neoformans can enlarge its size to form titan cells during infection, and its diameter can reach up to 100 µm. Clinical reports about cryptococcal titan cells are rare. Most studies focus on aspects of animal models of infection with titan cells. Herein, we report the clinical and imaging characteristics and histopathologic features of 3 patients with titan cells and 27 patients with pathogens of typical size, and describe the morphological characteristics of titan cells in details. Histologically, 3 patients with titan cells show necrosis, fibrosis and macrophage accumulation. The titan cells appear in necrotic tissue and between macrophages, and have thick wall with unstained halo around them and diameters range from 20 to 80 µm with characteristic of narrow-necked single budding. There are also organisms with typical size. All 27 patients with normal pathogens show epithelioid granulomatous lesions. There is no significantly difference in clinical and imaging feature between the two groups. Cryptococcus neoformans exhibits a striking morphological change for the formation of titan cells during pulmonary infection, which will result in misdiagnosis and under diagnosis. The histopathological changes may be new manifestation, which need to be further confirmed by the study with animal models of infection and the observation of more clinical cases. Careful observation of the tissue sections is necessary.

Diagnostic problems related to acute fibrinous and organizing pneumonia: misdiagnosis in 2 cases of lung consolidation and occupying lesions.

Acute fibrinous and organizing pneumonia (AFOP) is a histological pattern characterized by intra-alveolus fibrinous deposition accompanied with a spectrum of clinical condition. It also presents in other types of lung lesions, thus renders risks to its diagnosis with small biopsies. Here we present 2 cases of lung consolidation and occupying lesions with typical histological presentation of AFOP. One case is tuberculosis presented as massive lung consolidation, initially treated as AFOP, and eventually progressed to bilateral military tuberculosis. The other case presented an occupying mass in the lung which was initially suspected to be an inflammatory mass with AFOP. Lobectomy revealed a poorly-differentiated adenocarcinoma, with AFOP pattern present in the peripheral tissues of the neoplastic mass. In conclusion, we suggest that it is not preferable to diagnose idiopathic AFOP in lung consolidation and occupying lesions before excluding other types of lesions. The diagnostic significance of AFOP should be deliberated.

[The clinicopathological features of acute fibrinous and organizing pneumonia].

OBJECTIVE: To improve understanding of the clinical, radiological and pathological characteristics of acute fibrinous and organizing pneumonia (AFOP). METHODS: The clinical data of 5 AFOP patients were retrospectively analyzed. AFOP was diagnosed via percutaneous lung biopsy guided by chest computerized tomography (CT) in the Affiliated Drum Tower Hospital of Nanjing University Medical School during March 2011 to June 2012. The clinical, radiological and pathological characteristics of those patients were summarized. RESULTS: Among the 5 patients, 2 were male and 3 were female, aging 43-61 years. They were all subacute onset. The main clinical manifestations were dyspnea, productive cough, fever and chest pain with hypoxemia via blood gas analysis. Bilateral infiltrates with diffuse and pathy distribution were the predominant features in chest HRCT. The pathological examination revealed slightly widened alveolar septa, 1ymphocyte and plasma cell infiltration and the presence of intra-alveolar fibrin in the form of fibrin "balls" (organization) within the alveolar spaces. No neutrophil, and eosinophil infiltration and hyaline membrane formation were detected, which was different from other well-recognized histologic patterns of acute lung injury, such as diffuse alveolar damage, cryptogenic organizing pneumonia and eosinophilic pneumonia. All patients were treated by corticosteroids and showed significant clinical and radiological improvement. CONCLUSIONS: AFOP has nospecific features, and its diagnosis depends on pathological examination. Treatment with corticosteroids is optimal. However, whether it is a unique interstitial disease needs to be further clinically investigated.

Differences in HER2 over-expression between proximal and distal gastric cancers in the Chinese population.

AIM: To investigate HER2 expression and its correlation with clinicopathological variables between proximal and distal gastric cancers (GC) in the Chinese population. METHODS: Immunostaining of HER2 was performed and scored on a scale of 0-3 in 957 consecutive GC cases, according to the revised scoring criteria of HercepTest(TM) as used in the ToGA trial. Correlations between HER2 expression and clinicopathologic variables of proximal (n = 513) and distal (n = 444) GC were investigated. RESULTS: Our results showed that HER2 expression was significantly higher in the proximal than in distal GC (P < 0.05). Overall, HER2 expression was significantly higher in male patients (P < 0.01), the Lauren intestinal type (P < 0.001), low-grade (P < 0.001) and pM1 (P < 0.01) diseases, respectively. There was a significant difference in HER2 expression among some pTNM stages (P < 0.05). In contrast, HER2 expression in the distal GC was significantly higher in male patients (P < 0.001), low-grade histology (P < 0.001), the Lauren intestinal type (P < 0.001), and pM1 (P < 0.001). In the proximal GC, however, higher HER2 expression scores were observed only in tumors with low-grade histology (P < 0.001) and the Lauren intestinal type (P < 0.001). CONCLUSION: HER2 over-expression in GC of Chinese patients was significantly more common in proximal than in distal GC, and significantly correlated with the Lauren intestinal type and low-grade histology in both proximal and distal GC, and with pM1 disease and male gender in distal GC.

Evaluation of a mitochondrial disease criteria scoring system on mitochondrial encephalomyopathy in Chinese patients.

Due to the complicated clinical features of mitochondrial encephalomyopathy, simplified mitochondrial disease criteria (MDC) have recently been established in Europe. This study evaluated the sensitivity and specificity of this scoring system in Chinese patients. Seventy-eight patients with suspected mitochondrial encephalomyopathy were recruited to be scored by the simplified MDC and were further classified into "possible" (2-4), "probable" (5-7), or "definite" categories (≥8). Significant differences were observed between the total scores in the mitochondrial encephalomyopathy group and the other myopathy group. In the mitochondrial encephalomyopathy group, 73.5% of patients had a score above 8, whereas in the other myopathy group, the "definite" percentage was only 3.2%, suggesting the proposed MDC scoring system has a high sensitivity for diagnosis of mitochondrial encephalomyopathy in China. Moreover, there were significant differences in the clinical scores and imaging portions of the MDC, suggesting that the simplified MDC may distinguish mitochondrial disorder from other multisystem disorders to aid in early diagnosis prior to a muscle biopsy.

[Expressions of caveolin-1 and extracellular matrix in lung tissues of patients with idiopathic pulmonary fibrosis].

OBJECTIVE: To investigate the expressions of caveolin-1, collagen-I, α-smooth muscle actin (α-SMA) and Smad in lung tissues of patients with idiopathic pulmonary fibrosis (IPF) and therefore to explore their potential roles in the pathogenesis of the disease. METHODS: Six patients with IPF confirmed pathologically by open lung biopsy in Department of Pulmonary Medicine, Affiliated Drum Tower Hospital of Nanjing University from January 2005 to December 2008 were studied. Diagnosis of IPF was made in accordance with the American Thoracic Society/European Respiratory Society Consensus Statement. At the same period, 6 normal lung samples were also obtained from patients with lung cancer by surgical resections as the control group. The level of caveolin-1 mRNA and protein, collagen-I, α-SMA and Smads in lung tissues were detected by RT-PCR, Western blot and immunohistochemistry. RESULTS: Compared with the control group, significantly reduced levels of caveolin-1 mRNA and protein (0.66 ± 0.19 vs 0.05 ± 0.02; 0.81 ± 0.11 vs 0.16 ± 0.05, P < 0.05) were observed in the lungs of patients with IPF. However, collagen-I (0.85 ± 0.11 vs 0.16 ± 0.04) and α-SMA (0.78 ± 0.08 vs 0.14 ± 0.05) proteins in the lung tissues of IPF patients were significantly increased as compared to the controls (P < 0.05). The expressions of p-Smad2 and p-Smad3 proteins were significantly increased (0.78 ± 0.08 vs 0.17 ± 0.04; 0.86 ± 0.07 vs 0.14 ± 0.04, respectively, P < 0.05), while that of Smad7 protein decreased (0.22 ± 0.05 vs 0.78 ± 0.08, P < 0.05) in the lungs of patients with IPF as compared with the control groups. CONCLUSION: The reduced expression of caveolin-1 in lung tissues of IPF may be related to the development and progress of pulmonary fibrosis.

Deletion of myosin light chain kinase in endothelial cells has a minor effect on the lipopolysaccharide-induced increase in microvascular endothelium permeability in mice.

There is a current view that myosin light chain kinase (MLCK) plays a critical role in endothelial permeability. To investigate the functions of MLCK in endothelial cells in vivo, we generated a mouse model in which MLCK was selectively deleted by crossing Mylk1 floxed mice with Tie2/cre transgenic mice. Knocking out Mylk1 from endothelial cells had no effect on the global phenotype of the mice, including body weight and blood pressure. Lipopolysaccharide (LPS)-mediated septic death was also not altered in the knockout (KO) mice. Consistently, LPS-induced inflammatory injury and the increase in microvascular permeability in the main organs, including the lung and the kidney, was not significantly attenuated in KO mice as compared with wild-type mice. However, the LPS-induced microvascular hyperpermeability of the esophagus and the eyeballs was attenuated in KO mice. We also found that the LPS-mediated increase in the number of caveolae in the endothelial cells of the esophagus was significantly reduced in KO mice. Our results do not support a role for endothelial cell MLCK in the pathogenesis of inflammatory diseases.

[Expression of caveolin-1 and extracellular matrix induced by transforming growth factor beta1 in human fetal lung fibroblasts].

OBJECTIVE: To investigate the expressions of caveolin-1, collagen-I and alpha-SMA in human fetal lung fibroblasts induced by transforming growth factor beta(1) (TGF-beta(1)). METHODS: Human fetal lung fibroblasts (HFLF) were cultured in vitro, and exposed to TGF-beta(1) with different final concentrations (2, 5, 10 microg/L). Cells without TGF-beta(1) exposure served as the control. Caveolin-1 mRNA and protein, collagen-I and alpha-SMA proteins in cell (at least 5 x 10(8)) lysates, were detected at different points after the treatment of TGF-beta(1), by RT-PCR, Western blot and Immunohistochemistry. Each experiment was repeated 3 times. One-way analysis of variance (ANOVA) was used to compare data among groups, and linear regression was established for correlation analysis. RESULTS: TGF-beta(1) reduced caveolin-1 mRNA and protein expressions in a dose- and time-dependent manner, measured by integral optical density. Compared with the control group (1.22 +/- 0.12 and 1.45 +/- 0.06), caveolin-1 mRNA and protein expressions (0.59 +/- 0.06 and 0.53 +/- 0.04) were significantly reduced, with statistical significance (F = 29.279 and F = 95.786, P < 0.01), in cells exposed to TGF-beta(1) (5 microg/L) for 12 h. The collagen-I and alpha-SMA protein expressions (1.35 +/- 0.09 and 0.75 +/- 0.06) measured by integral optical density increased after stimulation, peaked at 24 h in 5 microg/L TGF-beta(1) group. At that time point, the collagen-I and alpha-SMA protein expressions were 4.2 and 4.8 times of the control group (0.28 +/- 0.04 and 0.18 +/- 0.04), F = 81.221 and F = 65.477, P < 0.01. Caveolin-1 expression had a negative correlation with collagen-I (r = -0.923, P < 0.05) and alpha-SMA protein expression (r = -0.793, P < 0.05). CONCLUSION: The reduced caveolin-1, which was negatively correlated with expressions of collagen-I and alpha-SMA proteins in HFLF cells exposed to TGF-beta(1), may be related to the development and progress of pulmonary fibrosis.