LncRNA PITPNA-AS1/miR-223-3p/PTN axis regulates malignant progression and stemness in lung squamous cell carcinoma.

BACKGROUND: Long noncoding RNAs (lncRNAs) are a kind of molecule that cannot code proteins, and their expression is dysregulated in diversified cancers. LncRNA PITPNA-AS1 has been shown to act as a tumor promoter in a variety of malignancies, but its function and regulatory mechanisms in lung squamous cell carcinoma (LUSC) are yet unknown. METHODS: The mRNA and protein expression of genes were examined by RT-qPCR, western blot, and IHC assay. The cell proliferation, migration, invasion, and stemness were detected through CCK-8, colony formation, Transwell and spheroid formation assays. The CD44+ and CD166+ -positive cells were detected through flow cytometry. The binding ability among genes through luciferase reporter and RNA pull-down assays. The tumor growth was detected through in vivo nude mice assay. RESULTS: The lncRNA PITPNA-AS1 had increased expression in LUSC and was linked to a poor prognosis. In LUSC, PITPNA-AS1 also enhanced cell proliferation, migration, invasion, and stemness. This mechanistic investigation showed that PITPNA-AS1 absorbed miR-223-3p and that miR-223-3p targeted PTN. MiR-223-3p inhibition or PTN overexpression might reverse the inhibitory effects of PITPNA-AS1 suppression on LUSC progression, as demonstrated by rescue experiments. In addition, the PITPNA-AS1/miR-223-3p/PTN axis accelerated tumor development in vivo. CONCLUSIONS: It is the first time we investigated the potential role and ceRNA regulatory mechanism of PITPNA-AS1 in LUSC. The data disclosed that PITPNA-AS1 upregulated PTN through sponging miR-223-3p to enhance the onset and progression of LUSC. These findings suggested the ceRNA axis may serve as a promising therapeutic biomarker for LUSC patients.

[A study on the feasibility of CT pulmonary function imaging for screening target lung lobes in bronchoscopic lung volume reduction].

OBJECTIVE: To study the feasibility of CT pulmonary function imaging as a tool for screening target lung lobes in bronchoscopic lung volume reduction. METHODS: A total of 31 patients with chronic bronchitis were included in the study and all of them underwent lung function tests, chest HRCT, and pulmonary ventilation-perfusion radionuclide scan. According to the lung function results, the patients were divided into 2 groups: 9 with normal lung function (normal group) and 22 with obstructive ventilatory dysfunction (emphysema group). The correlation between HRCT visual score, CT imaging parameters of lung function and pulmonary function results were analyzed. For each lung lobe, the correlation and difference between average CT values, pixel index (PI), and ventilation perfusion ratio (V/Q) were also analyzed to explore the reliability of CT lung function imaging for determining regional non-functional "target area" in candidate patients for bronchoscopic lung volume reduction. RESULTS: There was no correlation between HRCT visual scores and lung function test parameters (RV/TLC and FEV1/FVC) However, CT lung function imaging evaluation showed a good correlation with the lung function test parameters. For individual lung lobes, the average CT value and the pixel index (PI = -910 HU) were correlated with the corresponding lobe perfusion of the total lung perfusion percentage ratio. CONCLUSIONS: CT pulmonary function imaging results were objective, and had a good correlation with lung function tests and lung ventilation-perfusion scan results, which may be useful as a tool for screening target lung lobes in bronchoscopic lung volume reduction.

Customized self-expanding bare metal Y stents in the treatment of malignant carinal stenosis: a retrospective analysis.

BACKGROUND: Self-expanding Y metal stent insertion is a safe and effective palliative method for malignant lesions involving the lower trachea, tracheal carina, and the main-stem bronchi. However, the length and degree of airway stenosis in different patients tend to vary, which leads to a call for a customized Y stent that could achieve a better treatment effect. METHODS: This retrospective analysis included patients who received customized self-expanding bare metallic Y stents for malignant carinal stenosis at Beijing Tiantan Hospital, Capital Medical University between January 2007 and June 2020. CT scans and initial bronchoscopy were performed to provide reliable data for stent selection and size customization. Data on technical success, clinical success, and follow-up were analyzed. RESULTS: A total of 36 patients (26 males and 10 females; median age, 61 years; age range, 30-83 years) were enrolled. Technical success was 97.2% (35/36), while clinical success was 97.2% (35/36). There was no procedure-related mortality. Out of 35 patients, 4 (11.4%) had stent-associated complications that did not affect the procedure of stent insertion. Re-stenosis of the stent due to tumor progression was the main mid- and long-term stent-related complication (65% and 57.1%, respectively), followed by stent fractures (5% and 14.3%, respectively). CONCLUSIONS: The current study described the design and insertion of customized self-expanding bare metal Y-stents and demonstrated the feasibility of their use for maintaining tracheal and main-stem bronchus patency in malignant carinal stenosis. This approach could be used as a bridging method before commencing adjuvant therapy and final palliative therapy for the relief of symptoms.

[Effect of different root canal file tapers on fracture strength of root canal wall].

PURPOSE: To compare the effects of different nickel-titanium rotary tapers on fracture strength of root canal and the application value of finite element analysis in root canal therapy. METHODS: Twenty four mandibular premolars were selected and all crowns were removed. All samples were randomly divided into 4 groups: A, B, C and D. Group A and C were instrumented with Z-K3 nickel titanium file as 0.04 taper for root canal preparation. Group B and D were instrumented with Z-K3 nickel titanium file as 0.06 taper. Group C and D were sliced into 2 mm thick slices 3 times after root canal preparation. Two teeth were selected from group A and group B and scanned with micro-CT. The model was imported into different softwares to optimize. The assembly model was built and imported into ANSYS for finite element analysis. Universal testing machine and force bar were used to apply 100 N force to samples until fracture occurring at any place of tooth sample. The fracture load was recorded and comparative analysis was conducted. RESULTS: The results of finite element analysis showed that the maximum stress of 0.04, 0.06 taper models was 138.88 MPa and 78.812 MPa, respectively. The average fracture load of group A, B was 490.12 N and 501.83 N, respectively. In group C and D, the maximum average fracture load was 93.61 N and 141.53 N, respectively. From the neck to the middle and then to the tip, the average fracture load of root canal decreased in turn. CONCLUSIONS: For normal form mandibular premolars, the fracture strength of the root instrumented with 0.06 taper nickel titanium rotary file was significantly higher than that instrumented with 0.04 taper. Three dimensional finite element analysis could guide dentists to choose a suitable taper file in root canal treatment to reduce the incidence of root fracture.

Application of Micro-Tech stents in malignant carinal stenosis.

Malignant carinal stenosis is a disease process that is not always suitable for treatment with a Y-shaped stent. When one of the main bronchi is completely obstructed and cannot be recanalized, or its distal lung tissue has lost function, inserting a Y-shaped stent is infeasible. In this complex condition, a cone-shaped stent is selected to maintain the patency of the trachea and the other main bronchus. The efficacy of the bare cone-shaped Micro-Tech stent to treat malignant carinal stenosis was evaluated in the current study. The medical records of 47 patients with malignant carinal stenosis who underwent Micro-Tech stent placement between January 2004 and October 2017 in Beijing Tian Tan Hospital (Beijing, China) were analyzed retrospectively. A total of 47 bare Micro-Tech stents (28 Y-shaped and 19 cone-shaped) were successfully inserted in the patients. Following stent placement, immediate satisfactory results were achieved in all patients, especially an improvement of dyspnea (100%), cough (81.1%) and stridor (100%). The Karnofsky scores were significantly increased (P<0.001), and the American Thoracic Society Dyspnea Index values were significantly decreased (P<0.001). Following a median of 88 days, initial bronchoscopic interventions were performed for tumor overgrowth (84.6%), stent fracture (7.7%) and granulation tissue (7.7%). Restenting was performed in two patients due to tumor progression (n=1) and stent fracture (n=1). Removal of a Y-shaped stent was attempted in one patient, but failed, as the stent had become partly embedded in the airway mucosa. In conclusion, cone-shaped Micro-Tech stent placement maintained tracheal-unilateral main bronchus patency and benefitted patients with malignant carinal stenosis in whom Y-shaped stents were not suitable for insertion.

Comparison of clinical features and stent placement outcomes between airway stenosis caused by primary pulmonary malignancies and that caused by primary non-pulmonary malignancies.

BACKGROUND: Primary pulmonary malignancies (PPMs) and non-pulmonary malignancies (PNPMs) may result in airway stenosis requiring stenting. This study aimed to compare and evaluate the clinical features and stent placement outcomes of airway stenosis caused by PPMs and PNPMs. METHODS: A total of 141 patients with malignant airway stenosis who underwent Micro-Tech stent placements between January 2004 and October 2017 at Department of Respiratory Medicine, Beijing Tian Tan Hospital, Capital Medical University were divided into PPM (n = 100) and PNPM groups (n = 41). Patients' clinical features and stent placement outcomes were collected and analyzed. Chi-square test was used to compare the categorical variables, while independent- or paired-sample t test was used to compare the continuous variables. RESULTS: There were no significant differences in age, sex, treatment history, respiratory symptoms, and incidence of obstructive pneumonia between groups. Multiple airway involvement (63.0% vs. 31.7%; χ = 11.459, P = 0.001) and atelectasis (17.0% vs. 2.4%; χ = 5.536, P = 0.019) were more common in the PPM group, while extraluminal obstruction (24.4% vs. 6.0%; χ = 8.033, P = 0.005) was more common in the PNPM group. Before stenting, the American Thoracic Society Dyspnea Index (ADI) and Karnofsky Performance Scale (KPS) scores showed no significant differences between groups (all P > 0.05). After stenting, a satisfactory rate of symptom improvement was achieved in both groups (98.0% and 100.0% in the PPM and PNPM groups, respectively; χ = 0.016, P = 0.898); ADI and KPS scores, which showed no significant differences between groups (all P > 0.05), were significantly improved in each group (all P < 0.001). Complications after stenting could be effectively managed using bronchoscopic procedures. CONCLUSIONS: Among cases of malignant airway stenosis requiring stenting, those caused by PPM are more likely to involve multiple airways and are associated with atelectasis, while those caused by PNPM are more likely to cause extraluminal obstruction. Micro-Tech stent placement has the same immediate effect in terms of improvement in respiratory symptoms and performance status for both malignant airway stenosis caused by PPM and that caused by PNPM.

Scarring Airway Stenosis in Chinese Adults: Characteristics and Interventional Bronchoscopy Treatment.

BACKGROUND: Scarring airway stenosis is commonly seen in China as compared to other developed countries, due to the high prevalence of tuberculosis. Nowadays, interventional bronchoscopy treatment has been widely used to treat this disease in China. This study demonstrated the characteristics of scarring airway stenosis in Chinese adults and retrospectively evaluated the efficacy of interventional bronchoscopy treatment of this disease. METHODS: Patients with scarring airway stenosis from 18 tertiary hospitals were enrolled between January 2013 and June 2016. The causes, site, and length of scarring airway stenosis were analyzed, and the efficacy of the interventional bronchoscopy treatment was evaluated. RESULTS: The final study cohort consisted of 392 patients. Endotracheobronchial tuberculosis (EBTB) was the most common cause of scarring airway stenosis (305/392, 77.8%) in Chinese adults with a high rate of incidence in young women. The left main bronchus was most susceptible to EBTB, and most posttuberculosis airway scarring stenosis length was 1.1-2.0 cm. The average clinical success rate of interventional bronchoscopy treatment for scarring airway stenosis in Chinese patients is 60.5%. The stent was inserted in 8.7% scarring airway stenosis in China. CONCLUSIONS: Scarring airway stenosis exhibits specific characteristics in Chinese patients. Interventional bronchoscopy is a useful and safe treatment method for the disease.

Interventional Bronchoscopic Therapy in Adult Patients with Tracheobronchial Mucoepidermoid Carcinoma.

BACKGROUND: Tracheobronchial mucoepidermoid carcinoma (MEC) is a rare airway tumor in adults for which surgery is considered a first-line treatment. However, some patients already lost the best opportunity of a surgical intervention when diagnoses are confirmed, and surgery causes considerable trauma resulting in partial loss of pulmonary function. Moreover, the tumor is resistant to radiotherapy and chemotherapy. These factors make the treatment of tracheobronchial MEC challenging. This study aimed to evaluate the safety and efficacy of interventional bronchoscopic therapy in adult patients with tracheobronchial MEC. METHODS: We retrospectively analyzed the clinical manifestations, bronchoscopic interventions, complications, and outcomes of 11 adult patients with tracheobronchial MEC. Paired t-test was used to analyze the parameters of the American Thoracic Society Dyspnea Index and the Karnofsky Score before and after the first interventional bronchoscopic therapy. RESULTS: All tumors occurred in the main bronchus and were easily visualized by bronchoscopy. After interventional bronchoscopic therapy, the symptoms of all patients showed significant improvement. The American Thoracic Society Dyspnea Index decreased from 1.91 ± 1.22 to 0.27 ± 0.47 (t = 6.708, P < 0.001) and the Karnofsky Score increased from 78.18 ± 16.62 to 95.46 ± 8.20 (t = -5.190, P < 0.001). Bronchoscopic intervention did not result in serious complications or mortality. During the follow-up period between 3 and 96 months after the first therapy, the following results were noted: (1) among the eight patients with low-grade tracheobronchial MEC, only one patient had a relapse and agreed to surgical treatment; (2) among the three patients with high-grade tracheobronchial MEC, one patient required repeated bronchoscopic interventions, one patient died of pulmonary infection, and one patient died of systemic failure owing to tumor metastasis. CONCLUSIONS: Interventional bronchoscopic therapy, as an alternative treatment, shows promise in some adult patients with low-grade tracheobronchial MEC confined to the bronchus. However, for adult patients with high-grade tracheobronchial MEC, early diagnosis and surgical treatment are still strongly recommended.

Application of paclitaxel as adjuvant treatment for benign cicatricial airway stenosis.

Benign cicatricial airway stenosis (BCAS) is a potentially life-threatening disease. Recurrence occurs frequently after endoscopic treatment. Paclitaxel is known to prevent restenosis, but its clinical efficacy and safety is undetermined. Therefore, in this study, we investigated the efficacy and associated complications of paclitaxel as adjuvant treatment for BCAS of different etiologies. The study cohort included 28 patients with BCAS resulting from tuberculosis, intubation, tracheotomy, and other etiologies. All patients were treated at the Department of Respiratory Diseases, Beijing Tian Tan Hospital, Capital Medical University, China, between January 2010 and August 2014. After primary treatment by balloon dilation, cryotherapy, and/or high-frequency needle-knife treatment, paclitaxel was applied to the airway mucosa at the site of stenosis using a newly developed local instillation catheter. The primary outcome measures were the therapeutic efficacy of paclitaxel as adjuvant treatment, and the incidence of complications was observed as well. According to our criteria for evaluating the clinical effects on BCAS, 24 of the 28 cases achieved durable remission, three cases had remission, and one case showed no remission. Thus, the durable remission rate was 85.7%, and the combined effective rate was 96.4%. No differences in outcomes were observed among the different BCAS etiologies (P=0.144), and few complications were observed. Our results indicated that paclitaxel as an adjuvant treatment has greater efficacy than previously reported BCAS treatment methods.

Paclitaxel Drug-eluting Tracheal Stent Could Reduce Granulation Tissue Formation in a Canine Model.

BACKGROUND: Currently available silicone and metallic stents for tracheal stenosis are associated with many problems. Granulation proliferation is one of the main complications. The present study aimed to evaluate the efficacy of paclitaxel drug-eluting tracheal stent in reducing granulation tissue formation in a canine model, as well as the pharmacokinetic features and safety profiles of the coated drug. METHODS: Eight beagles were randomly divided into a control group (bare-metal stent group, n = 4) and an experimental group (paclitaxel-eluting stent group, n = 4). The observation period was 5 months. One beagle in both groups was sacrificed at the end of the 1st and 3rd months, respectively. The last two beagles in both groups were sacrificed at the end of 5th month. The proliferation of granulation tissue and changes in tracheal mucosa were compared between the two groups. Blood routine and liver and kidney function were monitored to evaluate the safety of the paclitaxel-eluting stent. The elution method and high-performance liquid chromatography were used to characterize the rate of in vivo release of paclitaxel from the stent. RESULTS: Compared with the control group, the proliferation of granulation tissue in the experimental group was significantly reduced. The drug release of paclitaxel-eluting stent was the fastest in the 1st month after implantation (up to 70.9%). Then, the release slowed down gradually. By the 5th month, the release reached up to 98.5%. During the observation period, a high concentration of the drug in the trachea (in the stented and adjacent unstented areas) and lung tissue was not noted, and the blood test showed no side effect. CONCLUSIONS: The paclitaxel-eluting stent could safely reduce the granulation tissue formation after stent implantation in vivo, suggesting that the paclitaxel-eluting tracheal stent might be considered for potential use in humans in the future.

Nonstent Combination Interventional Therapy for Treatment of Benign Cicatricial Airway Stenosis.

BACKGROUND: Benign cicatricial airway stenosis (BCAS) is a life-threatening disease. While there are numerous therapies, all have their defects, and stenosis can easily become recurrent. This study aimed to investigate the efficacy and complications of nonstent combination interventional therapy (NSCIT) when used for the treatment of BCAS of different causes and types. METHODS: This study enrolled a cohort of patients with BCAS resulting from tuberculosis, intubation, tracheotomy, and other origins. The patients were assigned to three groups determined by their type of stenosis: Web-like stenosis, granulation stenosis, and complex stenosis, and all patients received NSCIT. The efficacy and complications of treatment in each group of patients were observed. The Chi-square test, one-factor analysis of variance (ANOVA), and the paired t -test were used to analyze different parameters. RESULTS: The 10 patients with web-like stenosis and six patients with granulation stenosis exhibited durable remission rates of 100%. Among 41 patients with complex stenosis, 36 cases (88%) experienced remission and 29 cases (71%) experienced durable remission. When five patients with airway collapse were eliminated from the analysis, the overall remission rate was 97%. The average treatment durations for patients with web-like stenosis, granulation stenosis, and complex stenosis were 101, 21, and 110 days, respectively, and the average number of treatments was five, two, and five, respectively. CONCLUSIONS: NSCIT demonstrated good therapeutic efficacy and was associated with few complications. However, this approach was ineffective for treating patients with airway collapse or malacia.