Cerebral arterial air embolism after endobronchial electrocautery: a case report and review of the literature.

BACKGROUND: Endobronchial electrocautery is a common and safe therapeutic endoscopic treatment for malignant airway obstruction. Cerebral arterial air embolism (CAAE) is a rare but potentially fatal complication of endobronchial electrocautery. CASE PRESENTATION: We present the first case of cerebral arterial air embolism after endobronchial electrocautery. A 56-year-old male with a pulmonary tumour in the right upper lobe received repeated endobronchial electrocautery. During the procedure, he experienced unresponsiveness, hypoxemia and bradycardia, and he developed tetraplegia. Brain computed tomography showed several cerebral arterial air emboli with low-density spots in the right frontal lobe. He received hyperbaric oxygen therapy with almost full recovery, except for residual left-sided weakness. CONCLUSIONS: General physicians should realize that CAAE may be a possible complication of endobronchial electrocautery. Several measures, including avoiding positive pressure, lowering ventilatory pressures if possible, avoiding advancing the bronchoscope to occlude the bronchus and using the non-contact technique, should be used to prevent this devastating complication.

Structurally diverse isoquinoline alkaloids from the barks of Alangium salviifolium (L. f.) Wangerin and their cytotoxicity.

Eleven undescribed isoquinoline alkaloids (1-8, 14, 15, and 24), along with 19 analogues (9-13, 16-23, and 25-30) were isolated from the barks of Alangium salviifolium. The structures of the undescribed compounds were elucidated through the analysis of their HR-ESI-MS, 1D and 2D NMR, IR, UV, and X-ray diffraction. The absolute configuration of 8 was established via the ECD calculation. Notably, compounds 1/2 and 3/4 were two pairs of C-14 epimers. The isolated alkaloids were evaluated for their cytotoxicity against various cancer cell lines, including SGC-7901, HeLa, K562, A549, BEL-7402, HepG2, and B16, ß-carboline-benzoquinolizidine (14-22) and cepheline-type (24-28) alkaloids exhibited remarkable cytotoxicity, with IC50 values ranging from 0.01 to 48.12 µM. Remarkably, compounds 17 and 21 demonstrated greater cytotoxicity than the positive control doxorubicin hydrochloride. Furthermore, a significant proportion of these bioactive alkaloids possess a C-1' epimer configuration. The exploration of their structure-activity relationship holds promise for directing future investigations into alkaloids derived from Alangium, potentially leading to novel insights and therapeutic advancements.

MIP-T3 Expression Associated with Defects of Ciliogenesis in Airway of COPD Patients.

Introduction. Some studies have found that cilia were shorter in COPD smokers than in nonsmokers or healthy smokers. However, the structural abnormalities of cilia and the cause of such abnormalities in COPD patients still remain unknown. Tumor necrosis factor alpha receptor 3 interacting protein 1 (MIP-T3) may play an important role in the progress of ciliary protein transporting. Objectives: This study aimed at exploring the dominated structural abnormalities of cilia and the involvement of MIP-T3 in the pathogenesis of cilia of COPD patients. Methods: Patients who accepted pulmonary lobectomy were divided into 3 groups: the chronic obstructive pulmonary disease (COPD) smoker group, the healthy smoker group, and the nonsmoker group, according to smoking history and pulmonary function. The ultrastructure of cilia and the percentage of abnormal cilia were analyzed using a transmission electron microscope. Real-time PCR, immunohistochemical staining, and western blotting in bronchial epithelium were used to determine MIP-T3 mRNA and protein expression. The relationship between the percentage of abnormal cilia and lung function and MIP-T3 protein expression was analyzed. Results: Patients in the COPD smoker group had increased percentage of abnormal cilia comparing to both the healthy smoker group and the nonsmoker group (both P values <0.05). MIP-T3 expression was significantly declined in the COPD smoker group (P values <0.05). MIP-T3 expression was significantly declined in the COPD smoker group (P values <0.05). MIP-T3 expression was significantly declined in the COPD smoker group (P values <0.05). MIP-T3 expression was significantly declined in the COPD smoker group (. Conclusions: Our results suggested that the abnormal ciliary ultrastructure, which was common in COPD patients, might be due to MIP-T3 downregulation.

A large intrathoracic extramedullary hematopoiesis in alpha-thalassemia: A case report.

RATIONALE: Extramedullary hematopoiesis (EMH) is a rare disease characterized by the formation of hematopoietic elements outside the bone marrow driven by several hematological disease. To the best of our knowledge, EMH is relatively common in patient with beta-thalassemia or hereditary spherocytosis but rarely reported in patients with alpha-thalassemia. Here, we discuss a large intrathoracic EMH (measuring 95 mm × 66 mm) without presenting severe complications in alpha-thalassemia along with literature review. PATIENT CONCERNS: A 55-year-old Chinese female patient with alpha-thalassemia presented with ipsilateral pleural effusion and low hemoglobin level. DIAGNOSIS: Lung cancer was suspected at first and the mass was subjected to CT-guided percutaneous mediastinum biopsy and the pathology confirmed the final diagnosis of extramedullary hematopoiesis. INTERVENTIONS: Blood transfusion, thoracentesis and regular follow up were scheduled rather than surgical interventions or radiotherapy since our patient did not exhibit significant symptoms. OUTCOMES: After 6 months' regular follow up, the patient exhibited no evidence of disease progress. LESSONS: EMH is frequently misdiagnosed and should be differentiated from other masses in thoracic cavity, especially when the underlying hematological disease is discovered. Treatment methods of EMH include surgical resection, hyper-transfusion, hydroxyurea, low-dose radiation or a combination of them.

HMGCS2 functions as a tumor suppressor and has a prognostic impact in prostate cancer.

BACKGROUND: Accumulating studies reported that 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) may function as either an oncogene or a tumor suppressor in various human cancers. However, its involvement in prostate cancer (PCa) remains unknown. Therefore, the aim of this study was to investigate the clinical significance of HMGCS2 expression and its functions in PCa. METHODS: Expression levels of HMGCS2 mRNA and protein were detected by quantitative Polymerase Chain Reaction (qPCR), Western blot and immunohistochemistry, respectively. Associations of HMGCS2 expression with various clinicopathological features and patients' prognosis of PCa were statistically evaluated. Roles of HMGCS2 dysregulation in cell proliferation, invasion and migration of PCa cell lines were also determined. RESULTS: HMGCS2 protein expression was significantly reduced in PCa tissues compared to adjacent benign prostate tissues at protein levels (P < 0.05). Clinically, low HMGCS2 mRNA expression was dramatically associated with high Gleason score (GS) and pathological grade, as well as the presence of distant metastasis of PCa patients. In addition, PCa patients with low HMGCS2 mRNA expression more frequently had shorter disease-free survival and biochemical recurrence-free survival (all P < 0.05). HMGCS2 expression was identified as an independent factor to predict both disease-free and biochemical recurrence-free survivals of PCa patients. Moreover, loss-of-function experiments demonstrated that HMGCS2 knockdown-expression promotes cell proliferation, colony formation, invasion and migration of PCa cells in vitro and lower the apoptotic rate of PCa cells in vitro. CONCLUSIONS: Our data indicate that HMGCS2 may be capable of predicting the risk of biochemical recurrence in PCa patients after radical prostatectomy and functions as a tumor suppressor in PCa cancer, implying its related pathway potential as a drug candidate in anti-PCa therapy.

Expression and Clinical Significance of SOX9 in Renal Cell Carcinoma, Bladder Cancer and Penile Cancer.

BACKGROUND: Novel molecular markers are important diagnostic tools for the assessment of cancer progression and evaluation of effectiveness of the treatment. SOX9, a key regulator of developmental processes, is overexpressed in various neoplasms, such as prostate, breast, and colorectal cancers. However, the utilization of SOX9 as a biomarker for other urological cancers has not yet been investigated. METHODS: In the present study, paired patient tissue microarrays were analyzed by immunohistochemistry, and the SOX9 protein expression was quantitated as immunoreactive scores in patients with renal cell carcinoma (RCC), bladder cancer (BCa), and penile cancer (PC). RESULTS: In comparison with normal tissues, SOX9 protein expression was significantly upregulated in RCC (p < 0.001) and BCa (p < 0.001), and significantly correlated with the advanced pathological grade (RCC: p = 0.023) and clinical stage (RCC: p = 0.022 and BCa: p = 0.046) of patients. Based on the mRNA level in the TCGA dataset, SOX9 was upregulated in RCC with gender (p = 0.027), advanced pathological grade (p = 0.003) and advanced clinical stage (p = 0.001). Kaplan-Meier survival curves revealed that RCC patients with high SOX9 levels had shorter survival (p < 0.001). Further, high SOX9 expression was an independent prognostic factor for RCC patients (hazard ratio 0.056, 95% confidence interval 0.607-1.184; p < 0.001). CONCLUSION: These findings suggest that SOX9 may play an important role in tumor progression of RCC and BCa and it may be used as a biomarker of this malignancy.

Dysregulated microRNA-224/apelin axis associated with aggressive progression and poor prognosis in patients with prostate cancer.

Our previous study revealed that microRNA (miR)-224 down-regulation could promote tumor progression of prostate cancer (PCa) and might be associated with poor biochemical recurrence-free survival of patients with this malignancy. However, the underlying mechanisms of miR-224 have not been fully elucidated. In the current study, apelin (APLN) was identified as a target gene of miR-224. Forced expression of miR-224 inhibited PCa cell invasion and migration by suppressing the expression of APLN. In addition, the down-regulation of miR-224 was negatively correlated with the up-regulation of APLN mRNA in PCa tissues. Moreover, miR-224 down-regulation was significantly associated with advanced clinical stage (P = .027) and metastasis (P = .001), whereas APLN up-regulation more frequently occurred in PCa tissues with advanced pathologic stage (P = .003), metastasis (P < .001), and prostate-specific antigen failure (P = .001). Furthermore, patients with PCa in the miR-224-low/APLN-high group more frequently had shorter biochemical recurrence-free survival than those in groups with other expression patterns of the 2 molecules. Taken together, our data strongly confirmed for the first time that the dysregulated miR-224/APLN axis may be associated with tumorigenesis and aggressive progression of PCa. More importantly, miR-224 down-regulation and APLN up-regulation may synergistically predict biochemical recurrence-free survival in patients with PCa.

New method for noninvasive quantification of central venous pressure by ultrasound.

BACKGROUND: The central venous pressure (CVP) is essential for assessing the cardiac preload and circulating blood volume in clinic. The invasive CVP measurement by central venous catheter has been reported with various complications. The aim of this study was to develop a new noninvasive method for quantification of CVP by ultrasound. METHODS AND RESULTS: Seventy-six patients who had their CVP monitored for intraoperative or postoperative management were recruited. By accurate location of the collapse point of the internal jugular vein and the center of the right atrium using ultrasound imaging, the height of the fluid column between those 2 points was measured as the noninvasive CVP (CVPn). A total of 118 measurements were performed and compared with the invasive CVP (CVPi). Linear correlation analysis revealed a significant correlation between CVPi and CVPn (preoperative measurements, r=0.90; P<0.01 and postoperative measurements, r=0.93; P<0.01). Bland-Altman plots showed a good agreement between CVPi and CVPn with the mean difference of 0.22 mm Hg (preoperative measurements) and -0.09 mm Hg (postoperative measurements), respectively. CONCLUSIONS: The new noninvasive CVP quantification method based on the location of both the collapse point of internal jugular vein and the center of right atrium by ultrasound could be used as a reliable approach for monitoring the hemodynamic status in clinic.

Enhanced expression of centromere protein F predicts clinical progression and prognosis in patients with prostate cancer.

Centromere protein F (CENPF) is a protein associated with the centromere-kinetochore complex and chromosomal segregation during mitosis. Previous studies have demonstrated that the upregulation of CENPF may be used as a proliferation marker of malignant cell growth in tumors. The overexpression of CENPF has also been reported to be associated with a poor prognosis in human cancers. However, the clinical significance of CENPF in prostate cancer (PCa) has not yet been fully elucidated. Thus, the aim of the present study was to determine the association of CENPF with tumor progression and prognosis in patients with PCa. The expression of CENPF at the protein level in human PCa and non-cancerous prostate tissues was detected by immunohistochemical analysis, which was further validated using a microarray-based dataset (NCBI GEO accession no: GSE21032) at the mRNA level. Subsequently, the association of CENPF expression with the clinicopathological characteristics of the patients with PCa was statistically analyzed. Immunohistochemistry and dataset analysis revealed that CENPF expression was significantly increased in the PCa tissues compared with the non-cancerous prostate tissues [immunoreactivity score (IRS): PCa, 177.98 ± 94.096 vs. benign, 121.30 ± 89.596, P < 0.001; mRNA expression in the dataset: PCa, 5.67 ± 0.47 vs. benign, 5.40 ± 0.11; P < 0.001]. Additionally, as revealed by the dataset, the upregulation of CENPF mRNA expression in the PCa tissues significantly correlated with a higher Gleason score (GS, P = 0.005), an advanced pathological stage (P = 0.008), the presence of metastasis (P < 0.001), a shorter overall survival (P=0.003) and prostate-specific antigen (PSA) failure (P < 0.001). Furthermore, both univariate and multivariate analyses revealed that the upregulation of CENPF was an independent predictor of poor biochemical recurrence (BCR)-free survival (P < 0.001 and P = 0.012, respectively). Our data suggest that the increased expression of CENPF plays an important role in the progression of PCa. More importantly, the increased expression of CENPF may efficiently predict poor BCR-free survival in patients with PCa.

Exposure to 1950-MHz TD-SCDMA electromagnetic fields affects the apoptosis of astrocytes via caspase-3-dependent pathway.

The usage of mobile phone increases globally. However, there is still a paucity of data about the impact of electromagnetic fields (EMF) on human health. This study investigated whether EMF radiation would alter the biology of glial cells and act as a tumor-promoting agent. We exposed rat astrocytes and C6 glioma cells to 1950-MHz TD-SCDMA for 12, 24 and 48 h respectively, and found that EMF exposure had differential effects on rat astroctyes and C6 glioma cells. A 48 h of exposure damaged the mitochondria and induced significant apoptosis of astrocytes. Moreover, caspase-3, a hallmark of apoptosis, was highlighted in astrocytes after 48 h of EMF exposure, accompanied by a significantly increased expression of bax and reduced level of bcl-2. The tumorigenicity assays demonstrated that astrocytes did not form tumors in both control and exposure groups. In contrast, the unexposed and exposed C6 glioma cells show no significant differences in both biological feature and tumor formation ability. Therefore, our results implied that exposure to the EMF of 1950-MHz TD-SCDMA may not promote the tumor formation, but continuous exposure damaged the mitochondria of astrocytes and induce apoptosis through a caspase-3-dependent pathway with the involvement of bax and bcl-2.

Autophagy potentiates the anti-cancer effects of the histone deacetylase inhibitors in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer death worldwide. Drug treatments for HCC have been largely unsuccessful. Histone deacetylase inhibitors can reactivate tumor suppressor genes in cancer cells and serve as potential anti-cancer drugs. Two potent HDAC inhibitors OSU-HDAC42 and SAHA induced autophagy in HCC cells as revealed by transmission electron microscopy, immunofluorescence and LC3-II accumulation. We found that SAHA and OSU-HDAC42 induced autophagy through downregulation of Akt/mTOR signaling and induction of ER stress response. Inhibition of autophagy by 3-MA or Atg5 knockout reduced SAHA-induced cytotoxicity, indicating that SAHA-induced autophagy led to cell death. Our results show that the combination of autophagy inducers with SAHA might be attractive for the treatment of HCC and pharmacological targeting of autophagy provides promise for the management of cancer therapy.

Inhibition of autophagy enhances anticancer effects of atorvastatin in digestive malignancies.

Preclinical and clinical studies have shown that statins, the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors with cholesterol-lowering properties, exhibited anticancer effects. However, the underlying mechanisms remain ill defined. In this study, we showed that atorvastatin could inhibit the growth of hepatocellular carcinoma (HCC) and colorectal carcinoma (CRC) cells via induction of apoptosis. Atorvastatin also induced autophagy that is a physiologic process involved in the turnover of intracellular organelles. Atorvastatin-induced autophagy was found to be inhibited by AMP-activated protein kinase (AMPK) small interfering RNA. Examination of HCC patients showed the positive correlation between AMPK activity and autophagic marker (beclin-1). Atorvastatin-induced AMPK activation could induce p21 expression, which was also positively correlated with beclin-1 expression in CRC patients. AMPK/p21 signaling caused endoplasmic reticulum (ER) stress response leading to the induction of autophagy. Inhibition of autophagy by an autophagic inhibitor bafilomycin A1 or genetic knockout of autophagy-related gene 5 enhanced atorvastatin-induced cytotoxicity and apoptosis. In summary, activation of AMPK by atorvastatin enhances p21 expression and ER stress response, leading to autophagy, which promotes survival of cancer cells. Combinations of atorvastatin with bafilomycin A1 provide a novel and promising strategy to improve the treatment of digestive malignancies.