The efficacy of endobronchial valves for the treatment of bronchopleural fistula: a single-arm clinical trial.

Background: A bronchopleural fistula (BPF) is defined as communication between the bronchus and pleural cavity, and it is a dreaded complication of severe pulmonary disease. Surgical intervention, pleurodesis, and prolonged chest tube drainage have several disadvantages. To overcome these, many attempts have been made to treat BPF with bronchoscopy, especially with the insertion of an endobronchial one-way valve (EBV). Endobronchial valves for the treatment of BPF which had less trauma, relatively short operation time, better safety, and patients are more likely to accept this operation. If there is a definite efficacy, it should be widely used in later clinical practice. This study aimed to confirm the efficacy of endobronchial valves for the treatment of BPF. Methods: We retrospectively reviewed data from 26 patients who were treated for BPF using an EBV between August 2017 and October 2020. This sample constitutes all patients treated in our hospital (Shanghai Pulmonary Hospital, Tongji University School of Medicine) for this condition and with this intervention during this timeframe. We collected general information about the patient, complications of the procedure, and chest tube indwelling to assess the efficacy and safety of the procedure. Results: A total of 26 patients underwent EBV placement procedures; left upper lobe (LUL) was the most common lobe in which the valves were placed. The underlying etiologies for BPF were postoperative BPF (50%; n=14), pneumothorax (15%; n=4), non-tuberculosis mycobacteria (NTM) (19%; n=5), and tuberculosis (12%; n=3). Eleven patients underwent chest tube insertion. The average chest tube duration in the group of patients before receiving valves was 66 days (median, 65 days; range, 14-187 days). The average duration after which the chest tube was removed was 17.5 days after EBV placement (median, 7 days; range, 2-90 days). The effective rate of EBV for the treatment of BPF was 73.1%. Patients for whom the valves were not removed, there were no valve related complications. Conclusions: EBV placement is a relatively mature procedure, which is safe and effective, and generates less trauma and fewer complications. And this intervention may be suitable for wide application in clinical practice.

From Social Networking Site Use to Subjective Well-Being: The Interpersonal and Intrapersonal Mediating Pathways of Prosocial Behavior among Vocational College Students in China.

In view of the growing importance of social networking sites (SNS) to adolescents and the mixed and inconclusive empirical evidence on the relationships between SNS use and their well-being, the present study aimed to investigate the associations of social function use intensity (SFUI) and entertainment function use intensity (EFUI) with adolescent life satisfaction and self-esteem, and examine the mediating roles that general prosocial behavior and school volunteering may play in the links. Drawing from the findings of a self-administered online survey with a valid sample of 3452 adolescents (mean age = 18.21) from 10 vocational colleges across four regions of China, our results demonstrated that there was an indirect positive effect of SFUI on adolescent life satisfaction and self-esteem via two interpersonal pathways of general prosocial behavior and school volunteering. We also discovered that there was an indirect negative effect of EFUI on adolescent life satisfaction and self-esteem via an intrapersonal pathway of school volunteering. Our findings provided empirical support for the differential effects of SFUI and EFUI on adolescent life satisfaction and self-esteem through the interpersonal and intrapersonal pathways, and unpacked the mediating roles of general prosocial behavior and school volunteering in these mechanisms.

Methylprednisolone Attenuates Lipopolysaccharide-Induced Sepsis by Modulating the Small Nucleolar RNA Host Gene 5/Copine 1 Pathway.

Sepsis has become a major public health problem worldwide. Methylprednisolone sodium succinate (MP) is a commonly used drug to prevent inflammation. However, the role and underlying mechanism of MP in sepsis remain vague. MP inhibited the lipopolysaccharide (LPS)-induced production of tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-17 and suppressed cell growth in alveolar type II epithelial cells (ATII cells). Small nucleolar RNA host gene 5 (SNHG5) expression was inhibited by LPS and restored by MP. Upregulation of SNHG5 inhibited the cellular role of LPS in ATII cells, and further, downregulation of SNHG5 inhibited the cellular role of MP in ATII cells under LPS conditions. SNHG5 elevated the expression of Copine 1 (CPNE1) by enhancing the mRNA stability of CPNE1. Increasing CPNE1 expression restored the silenced SNHG5-induced inhibitor role of MP in ATII cells under LPS conditions. Finally, MP attenuated lung injury and TNF-α and IL-17 secretion in an LPS-induced sepsis mouse model. Overall, this study investigated the mechanism underlying the effect of MP treatment in sepsis and, for the first time, revealed the important role of the SNHG5/CPNE1 pathway in the development and treatment of sepsis and the potential to serve as a diagnostic and therapeutic target for sepsis.

Lung cancer-associated mesenchymal stem cells promote tumor metastasis and tumorigenesis by induction of epithelial-mesenchymal transition and stem-like reprogram.

Mesenchymal stem cells (MSCs) have attracted more attention in antitumor therapy by using MSCs as vehicles or targeting modulators of MSCs. But their role and mechanisms in tumor progression are less known. In the present study, we successfully isolated pairs of MSCs from lung cancer (LC-MSCs) and adjacent tumor-free tissues. Based on the coculture system in vitro and animal studies in vivo, we originally found that LC-MSCs significantly promoted tumor metastasis and tumorigenesis both in vitro and in vivo. Partial epithelial-mesenchymal transition (EMT) was induced in lung cancer cells by LC-MSCs by the evidence of remarkable increase in snail and slug expression but not in other EMT-associated genes. The expression of stem related genes also escalated significantly. And spheroids perfectly formed when tumor cells were co-incubated with LC-MSCs. These results revealed a close link of partial EMT and acquisition of stem-like traits in lung cancer cells which was induced by LC-MSCs and greatly promoted metastasis and tumorigenesis in lung cancer. Our findings provided a new insight into LC-MSCs in tumor progression and helped to identify LC-MSCs as a potential vehicle or target for lung cancer therapy.

Association of serum asprosin concentrations with obstructive sleep apnea syndrome.

OBJECTIVE: Asprosin, a recently discovered adipokine, stimulates the release of hepatic glucose. The purpose of the current research was to determine the relation between serum asprosin and obstructive sleep apnea syndrome (OSAS). METHODS: The current investigation enrolled 152 patients with OSAS and 97 control subjects. Serum asprosin concentrations were measured and analyzed. RESULTS: Higher serum asprosin concentrations were found in patients with OSAS than in the controls. Logistic regression analysis demonstrated that serum asprosin concentrations were associated with an increased risk of OSAS. Patients with severe OSAS had significantly increased asprosin compared to mild and moderate groups. The group with moderate OSAS showed higher serum asprosin levels than the group with mild OSAS. Pearson correlation analysis demonstrated a positive relation between serum asprosin and disease severity. Simple linear regression analyses showed a significant correlation between serum asprosin with body mass index (BMI), fasting plasma glucose (FPG), homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides (TG), and apnea-hypopnea index (AHI), and negatively correlated with high-density lipoprotein cholesterol (HDL-C). Multiple linear regression analysis revealed a significant correlation between serum asprosin with BMI, FPG, HOMA-IR, TG, AHI, and HDL-C. CONCLUSION: There is a significant correlation between serum asprosin with the presence and severity of OSAS.

Memory stem T cells generated by Wnt signaling from blood of human renal clear cell carcinoma patients.

OBJECTIVE: Memory stem T cells (Tscm) have attracted attention because of their enhanced self-renewal, multipotent capacity, and anti-tumor capacities. However, little is known about Tscm in patients with renal clear cell carcinoma (RCC) and the role of Wnt signaling in these cells. We evaluated Tscm from RCC patients concerning their activation of Wnt signaling in vitro and explored the mechanism of preferential survival. METHODS: Flow cytometry identified surface markers and cytokines produced from accumulated Tscm in the presence of the glycogen synthase kinase beta inhibitor TWS119. Apoptosis was evaluated after induction using tumor necrosis factor-alpha. Immunofluorescence and Western blot analyses were used to investigate the activation of the nuclear factor-kappa B (NF-КB) pathway. RESULTS: RCC patients had a similar percentage of CD4+ and CD8+ Tscm as healthy donors. Activation of Wnt signaling by TWS119 resulted in the accumulation of Tscm in activated T cells, but reversal of differentiated T cells to Tscm was not achieved. Preferential survival of Tscm was associated with increased anti-apoptotic ability mediated downstream of the NF-КB activation pathway. CONCLUSIONS: The finding that Tscm can accumulate by Wnt signaling in vitro in blood from RCC patients will help in devising new cancer therapy strategies of Tscm-based adoptive immunotherapy, such as dendritic cell-stimulated Tscm, and T cell receptor or chimeric antigen receptor-engineered Tscm.

Human umbilical cord mesenchymal stem cells delivering sTRAIL home to lung cancer mediated by MCP-1/CCR2 axis and exhibit antitumor effects.

Mesenchymal stem cells (MSCs) are believed to be a potential vehicle delivering antitumor agents for their tumor-homing capacity, while the underlying mechanism is yet to be explored. The apoptotic ligand TNF-related apoptosis-inducing ligand (TRAIL) has been suggested as a promising candidate for cancer gene therapy owing to its advantage of selectively inducing apoptosis in cancer cells while sparing normal cells. An isoleucine zipper (ISZ) added to the N-terminal of secretable soluble TRAIL (sTRAIL) can generate the trimeric form of TRAIL (ISZ-sTRAIL) and increase its antitumor potential. However, the inefficient delivery and toxicity are still obstacles for its use. In this study, the migration of human umbilical cord mesenchymal stem cells (HUMSCs) to lung cancer was observed through transwell migration assay and animal bioluminescent imaging both in vitro and in vivo. We found that the homing ability of HUMSCs was suppressed after either knocking down the expression of monocyte chemoattractant protein-1(MCP-1) in lung cancer cells or blocking CCR2 expressed on the surface of HUMSCs, indicating the important role of MCP-1/CCR2 axis in the tropism of HUMSCs to lung cancer. Furthermore, we genetically modified HUMSCs to deliver ISZ-sTRAIL to tumor sites specifically. This targeted therapeutic system exhibited promising apoptotic induction and antitumor potential in a xenograft mouse model without obvious side effects. In conclusion, HUMSCs expressing ISZ-sTRAIL might be an efficient therapeutic approach against lung cancer and MCP-1/CCR2 axis is essential for the tumor tropism of HUMSCs.

Osteopontin is a novel prognostic biomarker in early-stage non-small cell lung cancer after surgical resection.

PURPOSES: Osteopontin (OPN), an extracellular matrix-secreted phosphorylated glycoprotein, has been reported overexpressed in many solid tumors. As an important part of lung cancer, the high recurrence of non-small cell lung cancer (NSCLC) also attracted great attention of scientists. METHODS: In this study, we investigated the expression of OPN and the relationship with prognosis of NSCLC patients. We measured the expression of OPN among 163 NSCLC samples by immunohistochemical method and compared the expression of these 28 matched cDNA between tumor and peritumoral tissue by real-time polymerase chain reaction. RESULTS: We demonstrated that the percentages of positive OPN expression is 66.8 % and OPN expression in tumor site was much higher than the tissue adjacent to carcinoma (p = 0.0046). By further analysis, we found that OPN expression was significantly correlated with poor prognosis of NSCLC. Moreover, for early-stage patients, OS and DFS rates of OPN (-) group were significantly higher than OPN (+) group. For advanced-stage patients, OPN expression was only associated with OS rates. CONCLUSIONS: These results suggest that OPN is commonly expressed in NSCLC and may guide the evaluation of prognosis with NSCLC, especially for early-stage patients.

Efficacy and safety of cinitapride in the treatment of mild to moderate postprandial distress syndrome-predominant functional dyspepsia.

GOALS AND BACKGROUND: Functional dyspepsia (FD) is a complex disease with a variety of dyspeptic symptoms. Little is known about the clinical efficacy of cinitapride, a 5-HT4 agonist and D2 antagonist, in treating FD. STUDY: This randomized, double-blind, double-dummy, positive-controlled study compared the efficacy and safety of cinitapride (1 mg) and domperidone (10 mg) tid for 4 weeks in 383 consecutive patients with mild to moderate, postprandial distress syndrome-predominant dyspeptic symptoms according to Rome III criteria. The primary endpoint was the noninferiority of cinitapride compared with domperidone in relief of symptoms. The overall patient evaluation of treatment and open gastric emptying effects of both drugs were treated as the secondary endpoints. RESULTS: The rates of symptom relief by cinitapride and domperidone after 4 weeks did not differ significantly on intension-to-treat analysis (85.8% vs. 81.8%, P=0.332). Cinitapride significantly reduced the overall severity of postprandial fullness, early satiation, and bloating (4.3±3.9 vs. 17.8±6.6, P<0.001); and it was superior to the effects of domperidone (5.4±4.9 vs. 18.4±6.9, P<0.001; P=0.021 between groups). Cinitapride also decreased the mean half-gastric emptying time from 131.1±119.4 to 86.5±18.7 minutes (P=0.0002). There was a positive relationship between symptoms and gastric emptying time (r=0.332, P=0.041). Cinitapride-related adverse events were observed in 9.1% of patients, including 1 patient with extrapyramidal symptoms. No patient experienced QT interval prolongation. CONCLUSIONS: This phase III trial has confirmed a noninferior efficacy of cinitapride over domperidone for patients with mild to moderate, postprandial distress syndrome-predominant FD. Cinitapride usage is well tolerated, but its cardiovascular events need further evaluation.