Effect of BTP2 on agonist-induced vasoconstriction in the mouse aorta in vitro.

BTP2 is a potent inhibitor of store-operated Ca2+ entry (SOCE), which plays a vital role in vasoconstriction. However, the direct effect of BTP2 on the contractile response remains unclear. Here, we investigated the effects and mechanisms of action of BTP2 in the mouse aorta. Isometric tension was measured using a Multi Myograph System with two stainless steel wires. Ca2+ transient was recorded by confocal laser scanning microscope. The results showed that BTP2 markedly suppressed vasoconstriction mediated by SOCE and Ca2+ influx mediated by SOCE. The cumulative concentration of BTP2 had no effect on the baseline of mouse aortic rings, whereas it increased vasoconstriction stimulated by 3 µmol/L Phenylephrine. BTP2 (1 µmol/L) significantly increased vasoconstriction induced by 3 µmol/L Phe or cumulative concentration. BTP2 also promoted noradrenaline-induced aortic contraction. However, Phe- and noradrenaline-induced contraction was not affected by 0.3 or 3 µmol/L BTP2, and BTP2 at 10 µmol/L significantly suppressed aortic contraction. BTP2 inhibited 5-HT-evoked contraction in a concentration-dependent manner. BTP2 at higher concentrations (>3 µmol/L) inhibited CaCl2 -induced and 60 mmol/L K+ -induced contraction with progressive reduction of maximal contraction in a concentration-dependent manner. These results suggest that 1 µmol/L BTP2 increases contraction evoked by α1 adrenoreceptor activation. BTP2 at higher concentrations may inhibit Cav1.2 channels.

Does the calcification of adamantinomatous craniopharyngioma resemble the calcium deposition of osteogenesis/odontogenesis?

AIMS: Calcification in adamantinomatous craniopharyngioma (ACP) is troublesome for surgical intervention. The aim of this study was to examine the osteogenic proteins that play important roles in the calcium deposition of the odontogenic/osteogenic tissues in craniopharyngioma. METHODS AND RESULTS: Craniopharyngiomas (n = 89) were investigated for the presence and expression pattern of the osteoinductive/odontoinductive factor bone morphogenetic protein-2 (Bmp2) and two osteoblastic differentiation makers, Runt-related transcription factor-2 (Runx2) and Osterix, using immunohistochemistry and Western blotting. Our results showed that Bmp2, Runx2 and Osterix levels increased in cases with high calcification and correlated positively with the degree of calcification in ACP, whereas they showed little or no expression in squamous papillary craniopharyngioma. In ACP, Bmp2 was expressed primarily in the stellate reticulum and whorl-like array cells; Runx2 and Osterix tended to be expressed in calcification-related epithelia, including whorl-like array cells and epithelia in/around wet keratin and calcification lesions. CONCLUSIONS: Our study indicated, for the first time, that osteogenic factor Bmp2 may play an important role in the calcification of ACP via autocrine or paracrine mechanisms. Given the presence of osteogenic markers (Runx2 and Osterix), craniopharyngioma cells could differentiate into an osteoblast-like lineage, and the process of craniopharyngioma calcification resembles that which occurs in osteogenesis/odontogenesis.

The establishment and validation of a prediction model for traumatic intracranial injury patients: a reliable nomogram.

Objective: Traumatic brain injury (TBI) leads to death and disability. This study developed an effective prognostic nomogram for assessing the risk factors for TBI mortality. Method: Data were extracted from an online database called "Multiparameter Intelligent Monitoring in Intensive Care IV" (MIMIC IV). The ICD code obtained data from 2,551 TBI persons (first ICU stay, >18 years old) from this database. R divided samples into 7:3 training and testing cohorts. The univariate analysis determined whether the two cohorts differed statistically in baseline data. This research used forward stepwise logistic regression after independent prognostic factors for these TBI patients. The optimal variables were selected for the model by the optimal subset method. The optimal feature subsets in pattern recognition improved the model prediction, and the minimum BIC forest of the high-dimensional mixed graph model achieved a better prediction effect. A nomogram-labeled TBI-IHM model containing these risk factors was made by nomology in State software. Least Squares OLS was used to build linear models, and then the Receiver Operating Characteristic (ROC) curve was plotted. The TBI-IHM nomogram model's validity was determined by receiver operating characteristic curves (AUCs), correction curve, Hosmer-Lemeshow test, integrated discrimination improvement (IDI), net reclassification improvement (NRI), and decision-curve analysis (DCA). Result: The eight features with a minimal BIC model were mannitol use, mechanical ventilation, vasopressor use, international normalized ratio, urea nitrogen, respiratory rate, and cerebrovascular disease. The proposed nomogram (TBI-IHM model) was the best mortality prediction model, with better discrimination and superior model fitting for severely ill TBI patients staying in ICU. The model's receiver operating characteristic curve (ROC) was the best compared to the seven other models. It might be clinically helpful for doctors to make clinical decisions. Conclusion: The proposed nomogram (TBI-IHM model) has significant potential as a clinical utility in predicting mortality in TBI patients.

Expression and clinical significance of HCCS1 in non-small cell lung cancer.

AIM OF THE STUDY: Hepatocellular carcinoma suppressor 1 (HCCS1) has been identified as a tumor suppressor gene in the high-frequency loss of heterozygosity (LOH) region on chromosome 17p13.3 in hepatocellular carcinoma (HCC). There was also a high frequency of LOH on chromosome 17p13.3 in non-small cell lung cancer (NSCLC). Therefore, the aim of this study was to explore the expression of HCCS1 in NSCLC as well as its clinical significance. MATERIAL AND METHODS: Real-time PCR and immunohistochemistry were performed to detect the expression level of HCCS1 mRNA and protein in NSCLC and noncancerous tissues, respectively. Further, we explored the relationship between HCCS1 expression and various clinical features in NSCLC. RESULTS: The mRNA and protein expression of HCCS1 were both significantly lower in NSCLC samples than those in noncancerous tissues. That is, the mRNA level of HCCS1 was 0.0044 ±0.0036 and 0.0067 ±0.0054 in NSCLC samples and noncancerous tissues, respectively. The protein level of HCCS1 was 4.67 ±1.15 and 6.13 ±1.24 in NSCLC samples and noncancerous tissues, respectively. Importantly, this difference in expression was significantly correlated with tumor lymph node metastasis (TNM) in NSCLC (p < 0.05), but not with gender and age of the patients, pathological types, TNM stages, or grades of cancers (p > 0.05). CONCLUSION: Our results suggest that HCCS1 may be involved in NSCLC carcinogenesis.

Efficacy of Qihuang decoction on enteric nervous system in rats after gastrectomy.

OBJECTIVE: To investigate the influence of Qihuang decoction on enteric nervous system after gastrectomy in rats. METHODS: The morphology, distribution and number of intestinal neurons in enteric nervous system (ENS) were observed by immunofluorescence labeling and confocal laser scanning microscopy. Reverse transcription-polymerase chain reaction and Western blot were used to detect the mRNA and protein expression of intestinal neurotransmitters and corresponding receptors in ENS. RESULTS: The morphology and distribution of enteric neurons in ENS were changed after gastrectomy, and these neurons in Qihuang decoction group were similar with that of sham operation group. The number of ACh and SP positive neurons, mRNA and protein expression of excitatory neurotransmitters (AChE, SP) and receptors (M3R, NK1R) were decreased after gastrectomy. And the intervention of Qihuang decoction could increase the number of ACh and SP positive neurons and promote the expression of their mRNA and protein. For vasoactive intestinal peptide (VIP) and nitric oxide synthase (NOS), the number of neurons and mRNA and protein expression of inhibitory neurotransmitters (VIP and NOS) and receptors (VIP2R) were increased after gastrectomy. And these rising indexes fall back after the intervention of Qihuang decoction. Besides, the intestinal propulsion rate in QH group was significantly increased than that in SEN and IEN group. CONCLUSIONS: These experimental results showed that after gastrectomy, early intervention with Qihuang decoction in small intestine will contribute to the postoperative recovery of enteric nervous system and intestinal propulsion rate, and consequently enhance gastrointestinal motility.

Impact of tobacco cessation education on behaviors of nursing undergraduates in helping smokers to quit smoking.

INTRODUCTION: Smoking continues to be a significant public health issue, but nursing students do not receive sufficient training on tobacco cessation education. Integrating the 5As behaviors for tobacco cessation into a compulsory course could improve nursing students' skills and increase their clinical behaviors for assisting patients in quitting smoking. The aim of this study was to evaluate the impact of evidence-based tobacco cessation education on the perceptions and behaviors of nursing students who are assisting patients to quit smoking. METHODS: A prospective single-group design was used to evaluate the perceptions and behaviors of 626 senior nursing students enrolled in an education program, at three time points: baseline, 3 months post education, and 6 months post education. Data were collected, before and after the tobacco cessation education, using assessment tools for knowledge, attitudes, and the 5As behaviors for assisting patients to quit smoking. RESULTS: A total of 572 senior students completed the baseline survey, 289 students completed the survey 3 months post education, 348 students completed the survey 6 months post education, and 285 students completed all three surveys. Knowledge and self-efficacy of tobacco cessation were improved dramatically (p<0.05) after the education program, compared with the baseline survey. At 6 months post education, compared with at 3 months post education, nursing students reported more interventions of asking, advising, assessing, assisting, and arranging smokers to quit smoking (p<0.05). CONCLUSIONS: The integration of tobacco cessation education into compulsory courses could improve clinical skills and enhance the behaviors of nursing students for assisting patients to quit smoking.

Necroptosis Signaling Pathways in Stroke: From Mechanisms to Therapies.

It has been confirmed that apoptosis, autophagy and necrosis are the three major modes of cell death. For a long time, necrosis is regarded as a deranged or accidental cell demise. In recent years, there is evidence showing that necrotic cell death can be a well regulated and orchestrated event, which is also known as programmed cell death or "necroptosis". Necroptosis can be triggered by a variety of external stimuli and regulated by a caspase-independent pathway. It plays a key role in the pathogenesis of some diseases including neurological diseases. In the past two decades, a variety of studies have revealed that the necroptosis related pathway is activated in stroke, and plays a crucial role in the pathogenesis of stroke. Moreover, necroptosis may serve as a potential target in the therapy of stroke because genetic or pharmacological inhibition of necroptosis has been shown to be neuroprotective in stroke in vitro and in vivo. In this review, we briefly summarize recent advances in necroptosis, introduce the mechanism and strategies targeting necroptosis in stroke, and finally propose some issues in the treatment of stroke by targeting necroptosis.

Genetic characterization of CRF01_AE full-length human immunodeficiency virus type 1 sequences from Fujian, China.

HIV-1 CRF01_AE is the main prevalent HIV-1 recombinant strain in China and the dominant strain in Fujian as well; therefore, obtaining and understanding the genetic characterization of this clade become important. To date only a few full-length HIV-1 CRF01_AE genomes from China have been sequenced. We reported 13 full-length HIV-1 CRF01_AE isolate sequences from Fujian, China. DNA was extracted, the 5' and 3' halves of each genome were separately amplified, and the PCR products were cloned and sequenced. The phylogenetic analysis of the 13 sequences showed that they clustered with HIV-1 CRF01_AE isolates; these isolates were separated into a few distinct subgroups and were dispersed among the Thailand isolates, and the intersample diversity among Fujian isolates was significantly high. The high gene diversity among Fujian HIV-1 CRF01_AE isolates indicates that the HIV-1 CRF01_AE viruses in Fujian may be transmitted from multiple introductions. The work is essential for the design and development of an effective AIDS vaccine for China.

[Application of muscle pedicled platysma myocutaneous flap in the reconstruction of buccal mucosa defects].

OBJECTIVE: This study aimed to explore the main features and advantages of the muscle pedicled platysma myocutaneous flap (PMF), the degree of improvement of flap harvest. To evaluate the application value of the flap in the reconstruction of buccal mucosa carcinoma defects. METHODS: Twenty-three patients received PMF with MacFee incision to reconstruct buccal mucosa defects that were caused by the resection of precancer lesions and benign and malignant tumors from August 2012 to April 2015. When elevating the cervical skin from the platysma, most of the subcutaneous tissue was preserved on the muscle. The continuity of the facial vessels was retained. The external jugular vein was preserved on the reverse side of the platysma. RESULTS: Twenty-one flaps survived completely, whereas the other two flaps presented partial skin loss. Two patients showed disturbed wound healing in the neck. Secondary healing was achieved after attentive wound care. All patients were followed up from 11 to 43 months. The function of the recipient sites recovered well. Except for the two patients with large-area scarring in the neck, the remaining cases presented satisfactory neck contours. No relapses were observed during the follow-up period. CONCLUSIONS: Compared with the traditional PMF, the muscle pedicled PMF provides a larger skin paddle and presents a better aesthetic and functional effect. Thus, this approach is a novel and ideal option for the restoration of buccal mucosa defects.

Dosimetric effect of multileaf collimator leaf width on volumetric modulated arc stereotactic radiotherapy for spine tumors.

This work aimed to study the dosimetric effect of multileaf collimator (MLC) leaf widths in treatment plans for patients receiving volumetric modulated arc therapy (VMAT) for spine stereotactic body radiation therapy (SBRT). Thirteen patients treated with spine SBRT were retrospectively selected for this study. The patients were treated following the protocol of the Radiation Therapy Oncology Group 0631 (RTOG 0631) for spine metastasis. The prescription dose was 16 Gy in 1 fraction to 90% of the target volume (V16 > 90%). The maximum spinal cord dose of 14 Gy and 10% of the spinal cord receiving < 10 Gy (V10) were the acceptable tolerance doses. For the purpose of this study, 2 dual-arc VMAT plans were created for each patient using 3 different MLC leaf widths: 2.5 mm, 4 mm, and 5 mm. The compliance with the RTOG 0631 protocol, conformity index (CI), dose gradient index (DGI), and number of monitor units (MUs) were compared. The average V16Gy of the targets was 91.8 ± 1.2%, 92.2 ± 2.1%, and 91.7 ± 2.3% for 2.5-mm, 4-mm, and 5-mm leaf widths, respectively (p = 0.78). Accordingly, the average CI was 1.45 ± 0.4, 1.47 ± 0.29, and 1.47 ± 0.31 (p = 0.98), respectively. The average DGI was 0.22 ± 0.04, 0.20 ± 0.06, and 0.22 ± 0.05, respectively (p = 0.77). The average maximum dose to the spinal cord was 12.45 ± 1.0 Gy, 12.80 ± 1.0 Gy, and 12.48 ± 1.1 (p = 0.62) and V10% of the spinal cord was 3.6 ± 2.1%, 5.6 ± 2.8%, and 5.5 ± 3.0% (p = 0.11) for 2.5-mm, 4-mm, and 5-mm leaf widths, respectively. Accordingly, the average number of MUs was 4341 ± 500 MU, 5019 ± 834 MU, and 4606 ± 691 MU, respectively (p = 0.053). The use of 2.5-mm, 4-mm, and 5-mm MLCs achieved similar VMAT plan quality as recommended by the RTOG 0631. The dosimetric parameters were also comparable for the 3 MLCs. In general, any of these leaf widths can be used for spine SBRT using VMAT.

Increased circulatory RAS activity can be inhibited by statins in patients with hypercholesterolemia.

OBJECTIVE: The objective of this paper is to investigate a profile on circulatory renin-angiotensin system (RAS) activity in hypercholesterolemic (HC) patients treated with statins. METHODS: Eighteen primary HC patients and 18 sex- and age-matched healthy adults were included in this study as controls. Total cholesterol (TC), triglyceride (TG), LDL-C, blood glucose, angiotensin-converting enzyme (ACE) activity, and angiotensin II (Ang II) levels were measured before and four and eight weeks after beginning statin treatment in the HC group. Similar measurements were taken in the control group at baseline. RESULTS: At baseline, TC, TG and LDL-C levels, as well as ACE activity and Ang II concentrations, were significantly higher in the HC group than in the control group. Based on the baseline data collection of 36 participants, there were significant positive correlations between ACE activity and TC (r = 0.54) or LDL-C (r = 0.51), and between Ang II level and TC (r = 0.34) or LDL-C (r = 0.27). TC, LDL-C, Ang II (35.46 ± 14.49 vs 71.10 ± 20.47 pg/ml, p < 0.05) levels and ACE activity (108.9 ± 51.9 vs 180.1 ± 71.3 U/L, p < 0.05) were decreased in HC patients eight weeks after starting statin treatment. In HC patients, RAS activity correlated positively with TC and LDL-C levels before and after treatment. CONCLUSIONS: In HC patients, lowering serum cholesterol with statins is associated with decreased circulatory RAS activity.

Interaction of sex and task differences in reminiscence.

Reminiscence values obtained from 84 subjects on two tracking tasks were examined for their dependence upon sex, task, task order, and repeated measurement within tasks. Females reminisced more than males on both tasks, while task differences were significant only for males. These effects (a) show that reminiscence is a more complexly determined phenomenon than most writers have assumed, and (b) argue for a broadcast empirical examination of other possible dependencies.