[Navigation-guided nasal endoscopy for removal of the cavernous hemangioma of the orbital apex through the sphenoid approach].

Objective: To explore the feasibility of navigation-guided nasal endoscopy for removal of the cavernous hemangioma of the orbital apex through the sphenoid approach. Methods: Retrospective case series study. From May 2012 to December 2019, 12 patients (12 eyes) with imaging findings of cavernous hemangioma in the orbital apex were collected at the Eye Hospital Affiliated to Nanchang University, including 3 males and 9 females aged 32 to 59 years. All patients underwent navigation-guided sinusoscopy through the sphenoid approach to remove the cavernous hemangioma of the orbital apex (video attached). Changes of visual function and complications after operation were analyzed. Results: In 3 patients without visual impairment, the postoperative visual function was still normal. Among the remaining 9 patients with preoperative visual impairment, visual function was fully recovered in 3 patients after operation, was improved in 2 patients, and had no change in 4 patients. There were no complications in 3 of the 12 patients, and 9 patients had transient, mildly limited intraocular rotation with diplopia after operation, which all returned to normal within 1 month. Conclusion: Navigation-guided sinus endoscopy through the sphenoid approach is effective and feasible in the removal of the cavernous hemangioma of the orbital apex. (Chin J Ophthalmol, 2021, 57: 837-843).

[Prevalence of CYP2C19 gene mutations in patients with coronary heart disease and its biological activation effect in clopidogrel antiplatelet response].

Objective: The purpose of this study was to investigate the effects of CYP2C19 gene mutations on clopidogrel antiplatelet activity in the patients with coronary heart disease treated by percutaneous coronary intervention. Methods: Patients with coronary heart disease, who hospitalized in the Second Affiliated Hospital of Nanchang University from March 2011 to June 2019, and healthy individuals with matching genetic background, gender, and age as controls were included in this study. Basic clinical data were analyzed and blood samples of all research subjects were obtained for extraction of DNA, and Sanger first-generation sequencing method was used to detect CYP2C19 gene mutation from full exon and exon and intron junction. CYP2C19 gene variations in patients with coronary heart disease were compared with the 1000 Genomes Browse database and the sequencing results of healthy controls to determine whether the gene variation was a genetic mutation or a genetic polymorphism. After that, PolyPhen-2 prediction software was used to analyze the harmfulness of gene mutations to predict the effect of mutations on protein function. The same dose of CYP2C19 wild-type plasmid and the CYP2C19 gene mutant plasmids were transfected into human normal liver cells HL-7702. After transfection of 24 h, the expression of CYP2C19 protease in each group was detected. The liver S9 protein was incubated with clopidogrel, acted on platelets to detect the platelet aggregation rate and the activity of human vasodilator-activated phosphoprotein (VASP). Results: A total of 1 493 patients with coronary heart disease (59.36%) were enrolled, the average age was (64.5±10.4) years old, of which 1 129 were male (75.62%). Meanwhile, 1 022 healthy physical examination volunteers (40.64%) were enrolled, and the average age was (64.1±11.0) years old, of which 778 were male (76.13%). A total of 5 gene mutations of CYP2C19 gene were identified in 12 patients (0.80%), namely, 4 known mutations T130K (1 case), M136K (6 cases), N277K (3 cases), V472I (1 case) and one new mutation G27V (1 case), no corresponding gene mutation was found in healthy controls. It was found that T130K and M136K were probably damaging, G27V was possibly damaging, and N277K and V472I were benign mutations. In vitro, we demonstrated that the platelet aggregation rate of the M136K gene mutation group was 24.83% lower than that of the wild type (59.58% vs. 34.75%; P<0.05), and the phosphorylated VASP level was 23.0% higher than that of the wild type (1.0 vs. 1.23; P<0.05). However, the platelet aggregation rate and phosphorylated VASP level were similar between of G27V, T130K, N277K, V472I gene mutation groups and wild type group (P>0.05). Conclusions: In this study, 5 gene mutations are defined in patients with coronary heart disease, namely G27V, T130K, M136K, N277K, V472I. In vitro functional studies show that CYP2C19 gene mutation M136K, as a gain-of-function gene mutation, can enhance the activation of CYP2C19 enzyme on clopidogrel, thereby inhibiting the platelet aggregation rate.

Study of the predictors for radiation pneumonitis in patient with non-small cell lung cancer received radiotherapy after pneumonectomy.

PURPOSE: To identify the valuable predictors of grade≥2 radiation pneumonitis (RP) in patient treated with radiotherapy after pneumonectomy for non-small cell lung cancer (NSCLC); and to construct a nomogram predicting the incidence of grade≥2 RP in such patients. PATIENTS AND METHODS: We reviewed 82 patients with NSCLC received radiotherapy after pneumonectomy from 2008 to 2018. The endpoint was grade≥2 RP. Univariate and multivariate regression analysis were conducted to evaluate significant factors of grade≥2 RP. Receiver operating characteristic (ROC) curve was used to establish optimal cutoff values and the nomogram was built to make the predictive model visualized. Descriptive analysis was performed on 5 patients with grade 3 RP. RESULTS: A total of 22(26.8%) patients developed grade 2 RP and 5(6.1%) patients were grade 3 RP. V5, V10, V20, V30, MLD, PTV, and PTV/TLV were associated with the occurrence of grade≥2 RP in univariate analysis, while none of the clinical factors was significant; V5(OR,1.213;95%CI,1.099-1.339; P<0.001) and V20(OR,1.435;95%CI,1.166-1.765; P=0.001) were the independent significant predictors by multivariate analysis and were included in the nomogram. The ROC analysis for the cutoff values for predicting grade≥2 RP were V5>23% (AUC=0.819, sensitivity:0.701, specificity:0.832) and V20>8% (AUC=0.812, sensitivity:0.683, specificity:0.811). Additionally, grade≥3 RP did not occur when V5<30%, V20<13% and MLD<751.2cGy, respectively. CONCLUSIONS: Our study showed that V5 and V20 were independent predictors for grade≥2 RP in NSCLC patients receiving radiotherapy after pneumonectomy. Grade 3 RP did not occur whenV5<30%, V20<13% and MLD<751.2cGy, respectively. In addition, patient underwent right pneumonectomy may have a lower tolerance to radiation compared to left pneumonectomy.

[Maternal periconceptional folic acid supplementation and its effects on the prevalence of fetal neural tube defects].

OBJECTIVE: To find out the status of folic acid supplementation among women, to evaluate the prevention effects on neural tube defects (NTDs), and to explore the factors impact on folic acid supplementation compliance. METHODS: Based on the routine data of 92 121 women in prenatal health care and birth defect surveillance system in Tongzhou District of Beijing from 2013 to 2018, we described the prevalence of periconceptional folic acid supplementation, pre-pregnancy folic acid supplementation and regularly folic acid supplementation (compliance supplementation). Trend χ2 tests were used to evaluate the change of folic acid supplementation prevalence. The prevalence difference among the women with folic acid supplementation and without supplementation were tested with Fisher's exact test. Factors asso-ciated with folic acid supplementation compliance rate were analyzed with univariate and multivariate Logistic regression model. RESULTS: The prevalence of periconceptional folic acid supplementation during the six years was 90.08% and it was increased from 2013 to 2018, but the rate of pre-pregnancy and regular supplementation was only 41.5% and declined from 2013 to 2018, especially 2013 to 2015. The prevalence of NTDs among the fetuses whose mothers took folic acid during periconceptional period was 5.5/10 000, while the prevalence for the fetuses whose mothers did not take folic acid was 19.7/10 000 (P < 0.001), the rates ratio was 27.9% (χ2=23.74, P < 0.001). The difference between the prevalence of NTDs among the fetuses whose mothers took folic acid only and multiple micronutrients was not statistically significant. After controlling the confounding factors, it was found that the compliant folic acid supplementation rates in women, whose household registrations were outside Beijing and whose education levels were junior high school or below, and who were younger than 25 years old, and who were multiparas and who were pre-pregnancy underweight or obese, were lower than those of the corresponding control groups (P < 0.05). CONCLUSION: The rate of folic acid supplementation among women in Tongzhou District of Beijing was relatively high, but their compliance was poor. Women who did not take folic acid during periconception seriously affected the prevention effect of NTDs. We should focus on women who are younger than 25 years old, lower educated, pre-pregnancy underweight or obese, multiparas and nonlocal household registers, in order to improve the periconceptional folic acid supplementation compliance and improve the effects of NTDs prevention.

Patient-derived organoids of non-small cells lung cancer and their application for drug screening.

Patient-derived organoids (PDOs) are emerging as preclinical models with promising values in personalized cancer therapy. The purpose of this study was to establish a living biobank of PDOs from patients with non-small cell lung cancer (NSCLC) and to study the responses of PDOs to drugs. PDOs derived from NSCLC were cultured in vitro, and then treated with natural compounds including chelerythrine chloride, cantharidin, harmine, berberine and betaine with series of concentrations (0.5-30 µM) for drug screening. Phenotypic features and treatment responses of established PDOs were reported. Cell lines (H1299, H460 and H1650) were used for drug screening. We successfully established a living NSCLC organoids biobank of 10 patients, which showed similar pathological features with primary tumors. Nine of the 10 patients showed mutations in EGFR. Natural compounds chelerythrine chloride, cantharidin and harmine showed anticancer activity on PDOs and cell lines. There was no significant difference in the 95% confidence interval (CI) for the IC50 value of chelerythrine chloride between PDOs (1.56-2.88 µM) and cell lines (1.45-3.73 µM, p>0.05). PDOs were sensitive to berberine (95% CI, 0.092-1.55 µM), whereas cell lines showed a resistance (95% CI, 46.57-2275 µM, p<0.0001). PDOs had a higher IC50 value of cantharidin, and a lower IC50 value of harmine than cell lines (p<0.05, 7.50-10.45 µM and 4.27-6.50 µM in PDOs, 3.07-4.44 µM and 4.69-544.99 µM in cell lines, respectively). Both PDOs and cell lines were resistant to betaine. Chelerythrine chloride showed the highest inhibitory effect in both models. Our study established a living biobank of PDOs from NSCLC patients, which might be used for high-throughput drug screening and for promising personalized therapy design.

LncRNA LOXL1-AS1 inhibited cell proliferation, migration and invasion as well as induced apoptosis in breast cancer via regulating miR-143-3p.

OBJECTIVE: In recent years, studies have shown that lncRNA plays an essential regulatory role in biological life activities. In disease and cancer research, the function of lncRNA is closely related to inflammatory response, tumor formation and cellular metabolism. Breast cancer is one of the most common malignant tumors in women. The research on the pathogenesis of breast cancer is the focus of current research. Although the regulatory mechanisms of some lncRNAs have been proven, the complexity of cancer regulation has led to incomplete research. MATERIALS AND METHODS: The expression of LOXL1-AS1 and miR-143-3p was measured using qRT-PCR. Western blot was used to detect CDK, Cyclin D1, MMP-2, MMP-9, Bcl-2, Bax and Cleaved caspase-3 protein expression. MTT assay and transwell assay were applied to analyze cell proliferation, migration and invasion, respectively. Cell apoptosis rate of transfected cells was measured with flow cytometry. Luciferase reporter assay was applied to verify the relationship between LOXL1-AS1 and miR-143-3p. RESULTS: In this study, we found that LOXL1-AS1 expression was induced while miR-142-3p expression was decreased in breast cancer tissues and cells, implying that LOXL1-AS1 and miR-143-3p play an important role in cell progression of breast cancer. Further investigation showed that silencing LOXL1-AS1 inhibited proliferation, promoted cell apoptosis and decreased the capacity of cell migrated and invasive in breast cancer cells. The analysis of luciferase reporter assay determined that LOXL1-AS1 directly targeted miR-143-3p in breast cancer cells. The rescue experiments further proved that miR-143-3p reversed the inhibited effects of si- LOXL1-AS1 on breast cancer cells. CONCLUSIONS: In this study, we verified that LncRNA LOXL1-AS1 inhibited cell proliferation, migration and invasion as well as induced apoptosis in breast cancer via regulating miR-143-3p, providing a novel therapeutic target and improving understanding of the regulatory mechanism of cell progression in breast cancer.

Clinical significance of lncRNA BCYRN1 in colorectal cancer and its role in cell metastasis.

OBJECTIVE: To explore the expression of long non-coding RNA (lncRNA) BCYRN1 and its clinical significance and function in colorectal cancer (CRC). PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to detect the expression of lncRNA BCYRN1 in CRC tissues and cells. The relationship between lncRNA BCYRN1 expression and CRC clinicopathological characteristics was statistically analyzed. Furthermore, the Kaplan-Meier curve was performed in survival analysis. In vitro study, transwell and Western blot assays were used to detect the metastasis ability of CRC cells. RESULTS: LncRNA BCYRN1 expression was markedly up-regulated in CRC; high expression of lncRNA BCYRN1 promoted tumor metastasis in CRC patients and suggested a poor prognosis. In vitro study, down-regulation of lncRNA BCYRN1 expression by si-BCYRN1 could significantly inhibit invasion and migration of CRC cells. CONCLUSIONS: LncRNA BCYRN1 was a novel factor involved in CRC progression, and constituted a potential biomarker and therapeutic target for the patients.

[Advances in the research and application of orbital blowout fracture repair material].

Orbital blowout fractures can easily lead to defects of the orbital wall. In order to restore the continuity of the bone wall and avoid a series of clinical symptoms caused by orbital contents herniation or incarceration, the site of the defect should be reconstructed. The effect of reconstruction depends on the choice of surgical plan and repair material. The typical materials for bone wall defect repair include bone sheet, high density porous polyethylene, titanium mesh, absorbable polymer, bioactive ceramics and tissue engineering bone. This paper reviews the research findings and application of material for repairing of orbital blowout fracture. (Chin J Ophthalmol, 2019, 55: 876-880).

[Application of three-dimensional printing combined with surgical navigation and endoscopy in orbital fracture reconstruction].

Objective: To evaluate the clinical effect of three-dimensional printing combined with surgical navigation and endoscopy for orbital fracture reconstruction. Methods: A case series study. Twenty-eight patients (28 eyes) with orbital fractures (20 males and 8 females, aged 10-61 years, with simple orbital fractures in 22 patients and composite orbital fractures in 6 patients) were treated with three-dimensional printing combined with surgical navigation and endoscopy for orbital fracture reconstruction at Affiliated Eye Hospital of Nanchang University from July 2016 to June 2018. With the help of three-dimensional printed models and guides, navigation positioning guidance and endoscopic visualization performance, the soft tissue incarcerated in the orbital fracture area was loosened, and the repair material was implanted (video attached). Postoperative follow-up was conducted at 1 week and 3 months. The follow-up observation included the best corrected visual acuity, diplopia, dyskinesia of the eyes, enophthalmos, and orbital volume. The data were analyzed by the paired t-test, Wilcoxon and the Mann-Whitney U rank sum test. Results: The best corrected visual acuity before and 1 week after surgery was 4.714±0.400 and 4.732±0.377, respectively, and the difference was not statistically significant (t=1.724, P=0.096). The enophthalmos before and 1 week after surgery was 2.2 (2.0-5.0) mm and 0.3 (0.0-2.3) mm, respectively, and the difference was significant (Z=-4.604, P<0.01). The orbital volume before and 1 week after surgery was 2 008.10 (6.84-11 200.00) mm(3) and 478.76 (5.01-7 286.00) mm(3), respectively, and the difference was statistically significant (Z=-3.735, P<0.01).The preoperative diplopia degree was 0, Ⅰ, Ⅱ, and Ⅲ in 14, 11, 3, and 0 eyes, while the degree of diplopia 3 months after surgery was 0, Ⅰ, Ⅱ, and Ⅲ in 22, 6, 0, and 0 eyes, respectively. The difference was statistically significant (Z=-2.359, P=0.018). The preoperative dyskinesia degree of the eyes was 0, Ⅰ, Ⅱ, and Ⅲ in 11, 11, 3, and 3 eyes, while the dyskinesia degree of the eyes 3 months after surgery was 0, Ⅰ, Ⅱ, and Ⅲ in 23, 5, 0, and 0 eyes, respectively. The difference was statistically significant (Z=-3.456, P=0.001). No implant infection, displacement, and other serious complications were observed during the follow-up of 3 to 12 months. Conclusions: Three-dimensional printing technology combined with nasal endoscopy and surgical navigation, which is applied in the reconstruction of orbital fracture, can significantly improve the symptoms of diplopia, ocular dyskinesia, and ocular depression. It is a feasible assistant method. (Chin J Ophthalmol, 2019, 55: 658-664).

CT-guided core needle biopsy of small (≤20 mm) subpleural pulmonary lesions: value of the long transpulmonary needle path.

AIM: To evaluate the accuracy and complications of computed tomography (CT)-guided core needle biopsy (CNB) of small (≤20 mm) subpleural pulmonary lesions with the use of the long transpulmonary needle path. MATERIALS AND METHODS: A retrospective study was undertaken comprising 235 patients who underwent CT-guided CNB of small (≤20 mm) subpleural pulmonary lesions. One of two needle paths was used: a long (≥10 mm) transpulmonary needle path (n=164, group A) or a short (<10 mm) transpulmonary needle path (n=71, group B). Diagnostic accuracy, pneumothorax, and bleeding rates were compared between the two groups. RESULTS: The diagnostic accuracy in group A was significantly higher than that in group B (93.9% versus 81.7%, p=0.004), particularly in patients with 5-10 mm lesions (89.2% versus 53.3%, p=0.013). The mean length of the transpulmonary needle path was 23.9 mm in group A and 5.9 mm in group B (p<0.001). The mean number of pleural punctures in group A was 1.01 and 1.11 in group B (p=0.016), but for patients with more than one puncture, the short transpulmonary path was not associated with a higher accuracy rate. The incidence of bleeding was 22% in group A and 9.9% in group B (p=0.028). CONCLUSION: Diagnostic accuracy for small subpleural pulmonary lesions with the use of the long transpulmonary needle path was higher than that with the use of the short transpulmonary needle path, especially for 5-10 mm lesions; however, the long transpulmonary needle path was associated with a higher rate of bleeding.

[Computer-aided assessment of liver fibrosis progression in patients with chronic hepatitis B: an exploratory research].

Objective: To establish automatic liver fibrosis classification models by using traditional machine learning and deep learning methods and preliminaryly evaluate the efficiency. Methods: Gray scale ultrasound images and corresponding elastic images of 354 patients, 247 males and 107 females, mean age (54±12) years undergoing partial hepatectomy in Zhongshan Hospital of Fudan University from November 2014 to January 2016 were enrolled in this study. By using traditional machine learning and deep learning methods, an automatic classification model of liver fibrosis stages (S0 to S4) were established through feature extraction and classification of ultrasound image data sets and the accuracy in different classification categories of each model were calculated, by using liver biopsy as the reference standard. Results: Pathological examination showed 73 cases in pathological stage S0, 40 cases in S1, 49 cases in S2, 41 cases in S3, and 151 cases in S4. The traditional machine classification model based on support vector machine (SVM) classifier and sparse representation classifier and the deep learning classification model based on LeNet-5 neural network, their accuracy rates in the two categories (S0/S1/S2 and S3/S4) were 89.8%, 91.8% and 90.7% respectively; the accuracy rates in the three categories (S0/S1 and S2/S3 and S4) were 75.3%, 79.4% and 82.8% respectively; the accuracy in the three categories (S0 and S1/S2/S3 and S4) were 79.3%, 82.7% and 87.2% respectively. Conclusions: Computer-aided assessment of liver fibrosis progression in patients with chronic hepatitis B has a high accuracy, and can achieve a more detailed classification. This method is expected to be applied in the non-invasive evaluation of liver fibrosis in patients with hepatitis B in clinical work in the future.

Pancreatitis-associated protein-1 suppresses apoptosis in cerulein-stimulated pancreatic acinar cells in response to nuclear factor-kappa B activation.

Pancreatitis is a disease for which there are numerous etiologies but no effective treatments. Although the expression of the pancreatitis-associated protein-1 (PAP-1) serves as a marker for the disease, its biological function is unknown. The present study was carried out to determine if PAP-1 performs a protective role against oxidative stress-induced pancreatic cell death. For this purpose, we used cerulein-stimulated pancreatic acinar AR42J cells as an experimental model of acute pancreatitis. First, we demonstrated that PAP-1 gene expression is increased by cerulein in a dose- and time-dependent manner. In parallel, the level of active nuclear factor kappaB (NF-κB) was found to be increased in cells treated with cerulein. To test whether activation of the oxidant-sensitive transcription factor NF-κB is mediated by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, the primary source of reactive oxygen species, cerulein-stimulated NADPH oxidase activity was suppressed by using the NADPH oxidase inhibitor diphenyleneiodonium and, separately, by anti-sense oligonucleotides directed against NADPH oxidase subunits p22phox and p47phox. We observed that a decrease in NADPH oxidase activity resulted in decreased NF-κB activation and decreased PAP-1 gene expression. To determine whether the cerulein-induced NF-κB activation involves PAP-1 expression, cells were transfected to overexpress the MAD3 double-point IκBα mutant. In response, NF-κB activation and PAP-1 gene expression were decreased. Lastly, we observed that the cerulein-induced reduction in cell viability and increase in apoptosis are reversed by overexpression of PAP-1 in PAP-1-transfected cells. Taken together, these results support the postulate that PAP-1 inhibits cerulein-induced apoptosis in response to NADPH oxidase-mediated NF-κB activation in pancreatic acinar cells.

[Clinical study of SMT-â ¡ video laryngoscope with difficult airway intubation in emergency department].

Objective: To observe the clinical feasibility and security of SMT-Ⅱ video laryngoscope in difficult airway intubation in emergency department. Methods: This study took 90 adults with difficult airway who were admitted to the rescue room of Jingxi court of Beijing Chao-Yang Hospital, Capital Medical University from January 2015 to December 2016.The patients were randomly divided into 2 groups(SMT-Ⅱ video laryngoscope group: n=45, Macintosh direct laryngoscope group: n=45), which were treated with endotracheal intubation and ventilator assisted ventilation.The evaluation of difficult mask ventilation(DMV) independent risk factor score, Wlison score, Cormack-Lehane grade, mouth opening, thyromental distance, visualization of the glottis, time for laryngoscopy, time for tracheal intubation, first-pass success rate of intubation, complications, mean arterial pressure(MAP) and heart rate(HR) before induction, after laryngoscopy, after induction, after intubation 5 minutes, 10 minutes were recorded.ANOVA, t-test, Chi-square test was used to analyze differences data, respectively. Results: There was no significant difference between the two groups in terms of gender, age, height, weight and other general data, mouth opening, DMV independent risk factor score, Wlison score, and thyromental distance(χ(2)=0.045, t=-0.367, t=0.684, t=0.511, t=0.330, t=-0.724, t=1.219, t=1.034, all P>0.05). A Cormack-Lehane grade Ⅰ or Ⅱ view were 44 cases in SMT-Ⅱ video laryngoscope group and 14 cases in Macintosh direct laryngoscope group. It significantly improved with the use of SMT- Ⅱ video laryngoscope, compared with Macintosh direct laryngoscope(χ(2)=52.096, P<0.01). The time to best view was shorter in SMT-Ⅱ video laryngoscope group compared to that in Macintosh direct laryngoscope group with (15.0±1.0) seconds vs. (24.2±3.4) seconds(t=-26.319, P<0.05). The tube passage time was shorter with SMT-Ⅱ video laryngoscope (31.6±4.3) seconds vs. (12.7±0.9) seconds(t=-21.698, P<0.05)). The first -pass success rates in SMT-Ⅱ video laryngoscope group and Macintosh direct laryngoscope group were 100% and 84.4%, respectively(χ(2)=5.577, P<0.05). For complications, pharyngorrhagia at intubation occurred in 1 case in SMT-Ⅱ video laryngoscope group and 9 cases in Macintosh direct laryngoscope group(χ(2)=5.513, P<0.05), dislocation of tooth at intubation occurred in 0 case in SMT- Ⅱ video laryngoscope group and 6 cases in Macintosh direct laryngoscope group (χ(2)=4.464, P<0.05). The mean arterial pressure values before induction, after laryngoscopy, after induction and after intubation 5 minutes, 10 minutes were (84.8±3.3), (89.2±3.6), (90.8±3.6), (86.6±3.4), (85.4±3.6) mmHg(1 mmHg=0.133 kPa) in SMT-Ⅱ video laryngoscope group and (85.8±3.1), (91.9±3.4), (96.1±2.9), (90.0±2.5), (86.5±2.9) mmHg in Macintosh direct laryngoscope group. There was a significant difference between the two groups at the 5-time points of MAP (F=16.619, P=0.000). The heart rate values before induction, after laryngoscopy, after induction and after intubation 5 minutes, 10 minutes were(77.4±4.3), (80.8±4.3), (83.3±4.9), (78.8±4.2), (76.9±4.2) rate/minutes in SMT-Ⅱ video laryngoscope group and (75.7±4.0), (85.3±4.4), (90.7±4.4), (84.3±4.1), (78.3±4.2) rate/minutes in the Macintosh direct laryngoscope group.There was a significant difference between the two groups at the 5-time points of HR(F=15.857, P=0.000). Conclusions: SMT-Ⅱ video laryngoscope uesd in difficult ariway enable better visualization of the glottic opening, short opertive time, enhance the success rate of intubation.It indicucates that SMT-Ⅱ video laryngoscope is safer than Macintosh direct laryngoscope in patients with difficult airway.

Research of the relationship between ß-catenin and c-myc-mediated Wnt pathway and laterally spreading tumors occurrence.

OBJECTIVE: We studied the relationship between the occurrence of laterally spreading tumors (LSTs) and the activation of Wnt/ß-catenin/c-myc pathway. PATIENTS AND METHODS: 20 cases of colorectal polypoid adenomas (PAs) tissue sample, 20 cases of LSTs tissue sample and 20 cases of colorectal cancer tissue sample were acquired, and positive expression of Wnt/ß-catenin/c-myc proteins were detected by immunohistochemical staining. In addition, relative expression levels of mRNA and protein were measured using RT-PCR and Western blotting method. RESULTS: The positive expression levels of Wnt/ß-catenin/c-myc protein in the colorectal cancer group were higher than that in LST group, and the value of the PAs group was the lowest; differences were statistically significant (p < 0.05). The relative expression levels of Wnt/ß-catenin/c-myc mRNA and protein in colorectal cancer group were higher than that in LST group, and the value of PAs group was the lowest; differences were statistically significant (p < 0.05). CONCLUSIONS: The activation level of the Wnt/ß-catenin/c-myc pathway has a close relation to the occurrence and deterioration of LSTs.

Mucin 1-mediated chemo-resistance in lung cancer cells.

Paclitaxel (PTX) is a commonly used drug to treat diverse cancer types. However, its treatment can generate resistance and the mechanisms of PTX-resistance in lung cancers are still unclear. We demonstrated that non-small cell lung cancers (NSCLCs) survive PTX treatment. Compared with the progenitor NSCLC A549 cells, the PTX-resistant A549 cells (A549/PTX) displayed enhanced sphere-formation ability. The proportion of the cancer stem cell marker, aldehyde dehydrogenase-positive cells, and epithelial-mesenchymal transition signaling protein levels were also elevated in A549/PTX. Importantly, the levels of oncoproteins phosphoinositide-3 kinase/Akt, mucin 1 cytoplasmic domain (MUC1-C) and ß-catenin were also significantly elevated in A549/PTX. Furthermore, nuclear translocation of MUC1-C and ß-catenin increased in A549/PTX. The c-SRC protein, an activator of MUC1-C, was also overexpressed in A549/PTX. These observations led to the hypothesis that enhanced expression of MUC1-C is associated with stemness and PTX resistance in NSCLCs. To test this, we knocked down or overexpressed MUC1-C in A549/PTX and found that inhibition of MUC1-C expression coupled with PTX treatment was sufficient to reduce the sphere-forming ability and survival of A549/PTX. In summary, our in vitro and in vivo studies have revealed a potential mechanism of MUC1-C-mediated PTX resistance and provided insights into a novel therapeutic measure for lung cancers.

NAMPT suppresses glucose deprivation-induced oxidative stress by increasing NADPH levels in breast cancer.

Nicotinamide phosphoribosyltransferase (NAMPT) is a rate-limiting enzyme involved in NAD+ biosynthesis. Although NAMPT has emerged as a critical regulator of metabolic stress, the underlying mechanisms by which it regulates metabolic stress in cancer cells have not been completely elucidated. In this study, we determined that breast cancer cells expressing a high level of NAMPT were resistant to cell death induced by glucose depletion. Furthermore, NAMPT inhibition suppressed tumor growth in vivo in a xenograft model. Under glucose deprivation conditions, NAMPT inhibition was found to increase the mitochondrial reactive oxygen species (ROS) level, leading to cell death. This cell death was rescued by treatment with antioxidants or NAD+. Finally, we showed that NAMPT increased the pool of NAD+ that could be converted to NADPH through the pentose phosphate pathway and inhibited the depletion of reduced glutathione under glucose deprivation. Collectively, our results suggest a novel mechanism by which tumor cells protect themselves against glucose deprivation-induced oxidative stress by utilizing NAMPT to maintain NADPH levels.

Usefulness of normal saline for sealing the needle track after CT-guided lung biopsy.

AIM: To determine whether the use of normal saline for sealing the needle track can reduce the incidence of pneumothorax and chest tube placement after computed tomography (CT)-guided lung biopsy. MATERIALS AND METHODS: A prospective, randomised, controlled trial enrolling 322 patients was conducted. All patients were randomly assigned to one of two groups: those in whom the needle track was not sealed with normal saline (n=161, Group A) and those who did receive normal saline (n=161, Group B). CT-guided biopsy was performed with coaxial technique. Normal saline, which ranged from 1-3 ml, was injected while the trocar needle was being withdrawn. Patient characteristics, lesion, and procedure variables were analysed as potential risk variables for occurrence of pneumothorax and chest tube placement. RESULTS: The incidence of pneumothorax was 26.1% in Group A and 6.2% in Group B (p<0.001). Nine patients in Group A and one patient in Group B required chest tube placement (p=0.010). Using multiple logistic regression analysis, smaller lesion size, greater needle-pleural angle, longer lesion-pleural distance, presence of emphysema, and no sealing the needle track with normal saline were significantly associated with an increased risk of pneumothorax, and that the latter three factors were also associated with an increased risk of pneumothorax requiring chest tube placement. CONLUSION: Normal saline for sealing the needle track significantly reduces the incidence of pneumothorax and prevents subsequent chest tube placement after CT-guided lung biopsy.

Lentivirus-mediated RASSF1A expression suppresses aggressive phenotypes of gastric cancer cells in vitro and in vivo.

Loss of Ras association domain family protein 1 isoform A (RASSF1A) expression is associated with the development of a variety of human cancers and the expression of carcinoembryonic antigen (CEA) frequently occurs in gastric cancer. This study investigated the effects of RASSF1A expression restoration using a hypoxia-inducible CEA promoter-driven vector on xenograft tumor growth in nude mice and on the in-vitro regulation of gastric cancer cell viability, cell cycle distribution, apoptosis, colony formation and invasion capacity. The data showed that the level of CEA mRNA and protein was much higher in gastric cancer SGC7901 cells than in a second gastric cancer cell line, MKN28, or in the MCF-10A normal epithelial breast cell line. RASSF1A expression was restored in SGC7901 cells compared with the negative control virus-infected SGC7910 cells. RASSF1A expression restoration significantly inhibited gastric cancer cell viability, colony formation and invasion capacity, but induced cell cycle arrest and apoptosis in vitro, especially under hypoxic culture conditions. At the gene level, restoration of RASSF1A expression under hypoxic culture conditions significantly suppressed matrix metalloproteinase-2 expression and prevented cyclinD1 expression. A nude mouse xenograft assay showed that the restoration of RASSF1A expression reduced gastric cancer xenograft formation and growth. In conclusion, the restoration of RASSF1A expression using a hypoxia-inducible and CEA promoter-driven vector suppressed aggressive phenotypes of gastric cancer cells in vitro and in vivo. These results suggest that LV-5HRE-CEAp-RASSF1A gene therapy may be a promising novel approach to treat advanced gastric cancer.

ECM1 regulates tumor metastasis and CSC-like property through stabilization of ß-catenin.

Extracellular Matrix Protein 1 (ECM1) is a marker for tumorigenesis and is correlated with invasiveness and poor prognosis in various types of cancer. However, the functional role of ECM1 in cancer metastasis is unclear. Here, we detected high ECM1 level in breast cancer patient sera that was associated with recurrence of tumor. The modulation of ECM1 expression affected not only cell migration and invasion, but also sphere-forming ability and drug resistance in breast cancer cell lines. In addition, ECM1 regulated the gene expression associated with the epithelial to mesenchymal transition (EMT) progression and cancer stem cell (CSC) maintenance. Interestingly, ECM1 increased ß-catenin expression at the post-translational level through induction of MUC1, which was physically associated with ß-catenin. Indeed, the association between ß-catenin and the MUC1 cytoplasmic tail was increased by ECM1. Furthermore, forced expression of ß-catenin altered the gene expression that potentiated EMT progression and CSC phenotype maintenance in the cells. These data provide evidence that ECM1 has an important role in cancer metastasis through ß-catenin stabilization.