Botulinum toxin in the treatment of sialorrhea in severe neurological patients with tracheotomy.

OBJECTIVE: To observe the clinical effect of botulinum toxin type A (BTA) injection into the salivary glands of the severe neurological patients with tracheotomy METHODS: Seven patients with severe neurological disorders after tracheotomy and obvious drooling symptoms were enrolled. BTA was injected into bilateral parotid glands and submandibular glands under the guidance of ultrasound. Unstimulated salivary flow rate (uSFR) and Drooling Severity and Frequency Scale (DSFS) were used to evaluate drooling before injection, 1 week, and 4 weeks after injection. We compared the extubation time, time of changing from balloon cannula to metal cannula, hospitalization time and incidence of recurrent pulmonary infection between these patients and other patients accepted conventional curation. RESULTS: (1) The drooling severity scale (DSFS-S), the drooling frequency scale (DSFS-F), the drooling frequency and severity scale total score (DSFS-T) were significantly lower at 4 weeks after BTA injection compared to prior-treatment (p < .001). (2) uSFR of 1 week and 4 weeks were both statistically decreased than the untreated condition (p < .001). (3) Compared with the conventional group, the time of changing from balloon cannula to metal cannula was shortened obviously (p < .05) and incidence of recurrent pulmonary infection was clearly decreased (p < .05) after BTA treatment CONCLUSION: Ultrasound-guided BTA injection into salivary glands can effectively reduce saliva secretion. We also found that the time of changing cannula was shortened obviously and the incidence of recurrent pneumonia infection was reduced. BTA injection of salivary glands to cure drooling could advance to the clinical therapy in severe neurological patients after tracheotomy.

Relationships of Low Serum Levels of Interleukin-10 With Poststroke Anxiety and Cognitive Impairment in Patients With Clinical Acute Stroke.

BACKGROUND AND PURPOSE: The relationships among interleukin (IL)-10 levels, anxiety, and cognitive status after stroke remain controversial. We aimed to determine the associations of serum IL-10 levels with poststroke anxiety (PSA) and poststroke cognitive impairment (PSCI). METHODS: We recruited 350 patients with stroke, of whom only 151 completed a 1-month follow-up assessment. The Mini Mental State Examination (MMSE) and Hamilton Anxiety Scale (HAMA) were used to assess the cognitive status and anxiety, respectively. Serum IL-10 levels were measured within 24 hours of admission. RESULTS: IL-10 levels were significantly lower in the PSA group than in the non-PSA group, and they were negatively associated with HAMA scores (r=-0.371, p<0.001). After adjusting for all potential confounders, IL-10 levels remained an independent predictor of PSA (odds ratio=0.471, 95% confidence interval=0.237-0.936, p=0.032). IL-10 levels were strongly correlated with behavior during interviews, psychic anxiety, and somatic anxiety. Patients without PSCI had higher IL-10 levels were higher in non-PSCI patients than in PSCI patients, and they were positively associated with MMSE scores in the bivariate correlation analysis (r=0.169, p=0.038), and also with memory capacity, naming ability, and copying capacity. However, IL-10 did not predict PSCI in the univariable or multivariable logistic regression. CONCLUSIONS: Low IL-10 levels were associated with increased risks of PSA and PSCI at a 1-month follow-up after stroke. Serum IL-10 levels may therefore be helpful in predicting PSA.

The clinical significance of neutrophil-to-lymphocyte ratio and monocyte-to-lymphocyte ratio in Guillain-Barré syndrome.

Purpose/Aim of the study: Guillain Barré syndrome (GBS) is a severe peripheral nervous disease that leads to muscle weakness and areflexia. We now commonly accept a synthesis that inflammation and immunity play key role in GBS pathogenesis. Many studies pointed out that neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) are novel promising markers of inflammation or immunity. Our study aimed to evaluate whether the NLR and the MLR were associated to GBS or not. MATERIALS AND METHODS: We measured blood cell count in 334 individuals including 117 GBS and 217 healthy controls. RESULTS: Our findings demonstrated that the GBS patients had higher levels of NLR and MLR than the healthy controls. The severe group also had higher levels of NLR and MLR compared to the mild group. We took the method of receiver-operating characteristic curve to find out the cut-off value of NLR for GBS occurrence and severity; it was 2.295 and 3.05, respectively. The cut-off values of MLR for GBS incidence and severity were the same, it was 0.235. CONCLUSION: In the setting of GBS, the NLR and MLR were significantly increased and they may be pathophysiologically and clinically relevant in GBS. The NLR and MLR would be new biomarkers of medical application.

Lipopolysaccharide-induced CCN1 production enhances interleukin-6 secretion in bronchial epithelial cells.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a clinical complication caused by primary or secondary lung injury, as well as by systemic inflammation. Researches regarding molecular pathophysiology of ALI/ARDS are immerging with an ultimate aim towards developing prognostic molecular biomarkers and molecule-based therapy. However, the molecular mechanisms concerning ALI/ARDS are still not completely understood. The purpose of the present study was to identify a crucial role of CCN1 in inflammatory microenvironment during ALI/ARDS and focus on a potential communication between CCN1 and interleukin-6 (IL-6) in the airway epithelial cells. Our data illustrated that the expression levels of CCN1 and IL-6 in bronchoalveolar lavage fluid (BALF) in a lipopolysaccharide (LPS)-induced ALI mouse model were significantly elevated and the pulmonary expression of CCN1 was restricted to bronchial epithelial cells. Interestingly, both endogenous and exogenous CCN1 stimulated IL-6 production in vitro. Furthermore, LPS-induced IL-6 production in a bronchial epithelial cell line was blocked by CCN siRNA whereas CCN1 induced by LPS was sensitive to PI3K inhibition. Together, our data indicate a linear signal pathway, LPS-CCN1-IL-6, existing in bronchial epithelial cells after LPS exposure. This finding may represent an additional mechanism and a novel target for development of therapy and biomarker on ALI/ARDS.

Can glypican-3 be a disease-specific biomarker?

BACKGROUND: Glypican-3 (GPC3) is a cell surface-bound proteoglycan which has been identified as a potential biomarker candidate in hepatocellular carcinoma, lung carcinoma, severe pneumonia, and acute respiratory distress syndrome (ARDS). The aim of our review is to evaluate whether GPC3 has utility as a disease-specific biomarker, to discuss the potential involvement of GPC3 in cell biology, and to consider the changes of GPC3 gene and protein expression and regulation in hepatocellular carcinoma, lung cancer, severe pneumonia, and ARDS. RESULTS: Immunohistochemical studies have suggested that over-expression of GPC3 is associated with a poorer prognosis for hepatocellular carcinoma patients. Expression of GPC3 leads to an increased apoptosis response in human lung carcinoma tumor cells, and is considered to be a candidate lung tumor suppressor gene. Increased serum levels of GPC3 have been demonstrated in ARDS patients with severe pneumonia. CONCLUSIONS: Glypican-3 could be considered as a clinically useful biomarker in hepatocellular carcinoma, lung carcinoma, and ARDS, but further research is needed to confirm and expand on these findings.

Thyroid hormone level is associated with the frequency and severity of Guillain-Barré syndrome.

OBJECTIVE: Guillain-Barré syndrome (GBS) is a neurodegenerative and inflammatory demyelination disorder, and oxidative stress is concerned with the pathogenesis of the disease. Also, we found that thyroid hormone level is correlated to the oxidative and antioxidant status in previous studies. Our study was aimed to find the possible relationship between the frequency and severity of GBS and thyroid hormone levels. MATERIALS AND METHODS: We measured serum levels of thyroid-stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyronine (FT3) in 238 individuals, including 90 GBS, 44 multiple sclerosis and 104 healthy controls. RESULTS: Our findings demonstrate that the patients with GBS had lower TSH and higher FT4, FT4/FT3 than healthy controls in the normal range. Furthermore, it was also shown in our study that TSH levels in patients with GBS were correlated with disease severity measured by the Hughes Functional Grading Scale. CONCLUSION: Lower TSH, higher FT4 and FT4/FT3 stand for the oxidative status and are associated with the incidence and severity of GBS.

STAT1 modification improves therapeutic effects of interferons on lung cancer cells.

BACKGROUND: Interferons (IFNs) have potent anti-proliferative, pro-apoptotic, and immunomodulatory activities against cancer. However, the clinical utility of IFNs is limited by toxicity and pharmacokinetics making it difficult to achieve sustained therapeutic levels especially in solid tumors. METHODS: Signal Transducer and Activator of Transcription 1 (STAT1) or a modified STAT1 (designated STAT1-CC) that is hyper-responsive to IFN were overexpressed in lung cancer SPC-A-1 and H1299 cells using lentiviral vectors. Transduction efficiency was monitored using enhanced green fluorescent protein (EGFP) expression. After transduction, cells were treated with interferon-gamma (IFN-γ) or interferon-beta (IFN-ß) and monitored for cell proliferation, migration, and invasiveness using Cell Counting Kit-8 and transwell chamber assays and for apoptosis using Annexin V detection by flow cytometry. In addition, levels of STAT1, STAT1 Tyr-701 phosphorylation (pSTAT1), fibronectin, and ß-catenin were determined using western blotting. In the case of IFN-γ stimulation, levels of S100A4, proliferating cell nuclear antigen (PCNA), and c-fos expression were also determined. RESULTS: We found that expression of STAT1 or STAT1-CC enhanced the effect of IFN-γ and, IFN-ß on inhibition of human lung cancer cell proliferation, migration and invasiveness. Moreover, STAT1 and STAT1-CC expression caused increases in pSTAT1 and decreases in fibronectin and ß-catenin levels. STAT1-CC showed increased effects compared to STAT1 on IFN-γ induced pSTAT1 and down-regulation of S100A4, PCNA, and c-fos levels. CONCLUSION: The results show that STAT1-CC exhibited more strength in improving the antitumor response of IFNs in lung cancer cells. Results from this study suggest that combined treatment of IFNs and STAT1-CC might be a feasible approach for the clinical management of lung cancer in the future.