Stigma and related influencing factors in postoperative oral cancer patients in China: a cross-sectional study.

PURPOSE: To examine the level of stigma and identify its influencing factors among postoperative oral cancer patients in China. METHODS: In total, 274 postoperative oral cancer patients were recruited from a Grade A Tertiary Hospital in China using convenience sampling methods. Patients completed the Social Impact Scale (SIS), Medical Coping Mode Questionnaire (MCMQ), Social Support Rating Scale (SSRS), and General Self-efficacy Scale (GSE). RESULTS: Stigma reported by postoperative oral cancer patients was moderate (50.17 ± 21.24). Stepped multiple linear regression showed that the related factors influencing their feelings of stigma were educational level (ß = - 0.110, P = 0.001), smoking (ß = - 0.152, P < 0.001), betel quid (ß = - 0.120, P = 0.001), tumor location (ß = - 0.390, P < 0.001), tumor stage (ß = 0.219, P < 0.001), self-efficacy (ß = - 0.253, P < 0.001), and confrontation (ß = - 0.117, P = 0.001) and avoidance (ß = 0.123, P < 0.001), which explained 74.2% of the total variation in stigma (F = 99.378, P < 0.001). CONCLUSIONS: Stigma was positively predicted by tumor stage and avoidance but negatively predicted by education level, smoking, betel quid, tumor location, confrontation, and self-efficacy. Further work should focus on developing interventions to reduce stigma by improving protective factors and decreasing risk factors.

ZNF251 promotes the progression of lung cancer by activating ERK signaling.

Aberrant activation of ERK signaling is a hallmark of lung cancer. Although constitutively activating mutations of EGFR and KRAS contribute to the hyperactivation of ERK1/2, other mechanisms remain elusive. In this study, the zinc finger protein ZNF251 was found to be upregulated in clinical lung cancer samples, and it promoted the growth of lung cancer cells and the growth of primary lung KPC cells from mouse models (Ad-Cre, KrasG12D , and P53f/f ). In studying the molecular mechanism, ZNF251 was found to inhibit the expression of dual-specificity phosphatase 6, a negative regulator of ERK activation, by directly binding to its promoter region. Taken together, our data indicate the tumor-promoting effects of ZNF251 in lung cancer and suggest that ZNF251 is a therapeutic target.

Psychological resilience and related influencing factors in postoperative non-small cell lung cancer patients: A cross-sectional study.

OBJECTIVE: The psychological resilience of postoperative non-small cell lung cancer (NSCLC) patients is influenced by many factors. The purpose of this study is to investigate the current state of psychological resilience and identify its influencing factors in postoperative NSCLC patients. METHODS: This descriptive cross-sectional study used a convenience sampling method and recruited 382 inpatients from two Class A hospitals in Hunan, China. The Connor-Davidson Resilience Scale (CD-RISC), Strategies Used by People to Promote Health (SUPHH), Medical Coping Modes Questionnaire (MCMQ), and Multidimensional Scale of Perceived Social Support (MSPSS) were used. RESULTS: Postoperative NSCLC patients' psychological resilience was at a low level, with a score of (57.18 ± 8.55). Stepped Linear Regression showed that the related influencing factors of psychological resilience of postoperative NSCLC patients were age (ß = -0.313, P < .001), family average income (ß = 0.143, P < .001), self-efficacy (ß = 0.416, P < .001), confrontation (ß = 0.116, P < .001) and acceptance-resignation (ß = -0.155, P < .001), which could explain 58.0% of the total variation in psychological resilience (F = 103.68, P<.001). CONCLUSIONS: Psychological resilience is positively predicted by average income, self-efficacy, confrontation, but negatively predicted by age and acceptance-resignation. Self-efficacy is the most important variable influencing psychological resilience in postoperative NSCLC patients. In the future, a series of targeted interventions need to be implemented to strengthen patients' self-efficacy and psychological resilience, which can also improve the quality of life of postoperative NSCLC patients.

Down-regulation of LATS2 in non-small cell lung cancer promoted the growth and motility of cancer cells.

LATS2 (Large tumor suppressor) has been reported to be dys-regulated in several cancer types. However, its function in non-small cell lung cancer (NSCLC) remains poorly understood. Here, it was found that the expression level of LATS2 was decreased in NSCLC tissues. Moreover, forced expression of LATS2 in NSCLC cells inhibited cell growth and migration, while knockdown of the expression of LATS2 promoted the tumorigenicity of NSCLC cells. Mechanistically, LATS2 was found to negatively regulate NF-κB signaling in NSCLC cells. Taken together, our study suggested that down-regulation of LATS2 was very important in the progression of NSCLC, and restoring the function of LATS2 might be a promising therapeutic strategy for NSCLC.

LATS2 inhibits the activity of NF-κ B signaling by disrupting the interaction between TAK1 and IKKß.

NF-κB signaling plays very important role in the tumorigenesis of nonsmall cell lung cancer (NSCLC). However, the molecular mechanisms for the dysregulation of NF-κB signaling in NSCLC have not been fully understood. In the previous reports, we have showed that large tumor suppressor gene 2 (LATS2) inhibited NF-κB signaling in NSCLC cells, whereas the details for the mechanism remain unknown. Here, we reported that LATS2 is a suppressor of tumor necrosis factor (TNF-α)-induced NF-κB signaling by inhibiting the interaction between TAK1 and IKKß. Overexpression of LATS2 largely blocked TNF-α-induced NF-κB activation and IκBα degradation, whereas knockdown of LATS2 showed the opposing results. Mechanistically, we identified that LATS2 interacted with IKKß and blocked the interaction between IKKß and TAK1. Our results indicate that LATS2 functions as a pivotal negative regulator in TNF-α-induced activation of NF-κB via disrupting the interaction of TAK1 with IKKß.

Downregulation of MED23 promoted the tumorigenecity of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most common tumors in the world. It is very urgent to develop new therapeutic strategies. MED23, a component of the mediator complex, is known as a hub to integrate various signaling pathways. However, the function of MED23 in ESCC remains unknown. Here, we found that the expression of MED23 was downregulated in the clinical ESCC samples and the expression of MED23 reversely correlated with tumor size and clinical stage. Moreover, overexpression of MED23 in ESCC cells inhibited cell growth dramatically, while downregulation of MED23 promoted the tumorigenecity of ESCC cells in vitro and in vivo. Mechanistically, knockdown the expression of MED23 inhibited cell apoptosis by downregulation of Bax, activated Caspase 3, activated Caspase 9 and upregulation of cyclinD1 and Bcl2. Taken together, our study revealed the suppressive role of MED23 in ESCC and MED23 might be an important therapeutic target in ESCC.

TRAF6 promoted the metastasis of esophageal squamous cell carcinoma.

Esophageal cancer is one of the most aggressive malignancies and has been ranked as the sixth leading cause of cancer-related death in the world. It is very urgent to find new therapeutic targets. Although tumor necrosis factor receptor-associated factor 6 (TRAF6) was initially identified as an adaptor for NF-κB signaling, recently it has been found to be involved in cancer by modulating various signaling pathways. In the previous study, we have found that TRAF6 promoted the growth of esophageal squamous cell carcinoma (ESCC) cell in vitro and in vivo. However, the effects of TRAF6 on the migration and metastasis of ESCC cells are poorly understood. Here, we found that TRAF6 promoted migration and metastasis of ESCC cells through modulating Ras signaling. Overexpression of TRAF6 promoted the migration of ESCC cells and immortalized esophageal epithelial cells, while knock down the expression of TRAF6 inhibited the migration and metastasis of ESCC cells in vitro and in vivo. Mechanically, TRAF6 binds Ras with its N-terminal and activated Ras signaling. Taken together, TRAF6 played an important role in the metastasis of ESCC and might be a promising therapeutic target.

HMGCR is necessary for the tumorigenecity of esophageal squamous cell carcinoma and is regulated by Myc.

Hydroxymethylglutaryl coenzyme A reductase (HMGCR), the rate-limiting enzyme of mevalonate pathway, has been involved in the tumorigenesis of several tumor types. Our previous study has showed that statin, the inhibitor of HMGCR, inhibited the tumorigenecity of esophageal squamous cell carcinoma (ESCC) in vitro and in vivo. However, the function of HMGCR in the carcinogenesis of ESCC cells remains unknown. In this study, we have observed the up-regulation of HMGCR in ESCC tissues compared with the paired normal tissues. Over-expression of HMGCR in ESCC cells promoted cell growth and migration, while knockdown of the expression of HMGCR inhibited the growth, migration and colony formation of ESCC cells in vitro and in vivo. Furthermore, we found that oncogene Myc positively regulated the expression of HMGCR. Taken together, our study revealed the pivotal function of HMGCR and mevalonate pathway in the progression of ESCC and supported the clinical application of statin.

Upregulation of mediator MED23 in non-small-cell lung cancer promotes the growth, migration, and metastasis of cancer cells.

Mediator complex subunit MED23 has been reported to facilitate the transformation induced by oncogenic Ras in non-small-cell lung carcinoma (NSCLC). However, the expression pattern and biological functions of MED23 in the progression of NSCLC are not fully understood. In this study, it was found that the expression of MED23 was significantly upregulated in NSCLC samples compared to their adjacent normal tissues. Moreover, in the biological function studies, overexpression of MED23 was further validated to promote the growth, migration, and metastasis of NSCLC cells, while knockdown of the expression of MED23 inhibited the growth, migration, and metastasis of NSCLC cells in vitro and in vivo. Mechanistically, MED23 was found to interact with beta-catenin and activate beta-catenin/TCF signaling. Our study demonstrated that MED23 played an oncogenic role in the progression of NSCLC and that MED23 might be a promising target for the treatment of NSCLC.

NSDHL promotes the degradation of sting in cholangiocarcinoma.

Metabolic enzymes play significant roles in tumor growth via nonmetabolic biological processes. However, more research is needed to understand their roles in immune modulation. This study revealed that 3-hydroxysteroid dehydrogenase (NSDHL) expression was elevated in cholangiocarcinoma. In vitro experiments demonstrated that NSDHL had no effect on the growth or invasion of cholangiocarcinoma cells in an artificial laboratory environment. However, NSDHL overexpression strongly enhanced the promotion of AKT/YAP-driven cholangiocarcinoma. NSDHL bound to STING and facilitated its degradation via ubiquitination. This inhibited the cyclic-GMP-AMP-synthase-STING signaling pathway and reduced the synthesis of IFNß. A study revealed an inverse relationship between the expression of NSDHL and the infiltration of NK cells, activated CD4+ T cells, and neutrophils in individuals who were diagnosed with cholangiocarcinoma. This study elucidates the role of NSDHL, in addition to its established metabolic functions, NSDHL regulates the cyclic-GMP-AMP-synthase signaling pathway. By exploring this interplay, this research enriches our understanding of the functions of NSDHL in terms of cellular dynamics, offering novel insights into the modulation of crucial biological pathways.

Tyrosine hydroxylase inhibits HCC progression by downregulating TGFß/Smad signaling.

The alteration of metabolic processes has been found to have significant impacts on the development of hepatocellular carcinoma (HCC). Nevertheless, the effects of dysfunction of tyrosine metabolism on the development of HCC remains to be discovered. This research demonstrated that tyrosine hydroxylase (TH), which responsible for the initial and limiting step in the bio-generation of the neuro-transmitters dopamine and adrenaline, et al. was shown to be reduced in HCC. Increased expression of TH was found facilitates the survival of HCC patients. In addition, decreased TH indicated larger tumor size, much more numbers of tumor, higher level of AFP, and the presence of cirrhosis. TH effectively impairs the growth and metastasis of HCC cells, a process dependent on the phosphorylation of serine residues (S19/S40). TH directly binds to Smad2 and hinders the cascade activation of TGFß/Smad signaling with the treatment of TGFß1. In summary, our study uncovered the non-metabolic functions of TH in the development of HCC and proposes that TH might be a promising biomarker for diagnosis as well as an innovative target for metastatic HCC.

TRAF6 promoted the tumorigenicity of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies worldwide. It is very urgent to understand the underlying molecular mechanism and develop new therapeutic strategy. Tumor necrosis factor receptor-associated factor (TRAF6), initially identified as a regulator of NF-κB, recently has been found to be involved in cancer by modulating various signaling pathways. However, the function of TRAF6 in ESCC is poorly understood. Here, we found that the expression of TRAF6 was upregulated in ESCC cell lines and clinical samples. Moreover, over-expression of TRAF6 in ESCC cells promoted cell proliferation, while downregulation of TRAF6 impaired the tumorigenicity of ESCC cells in vitro and in vivo. Mechanistically, TRAF6 inhibited cell apoptosis by downregulation of activated caspase 3 and cleaved poly ADP ribose polymerase and upregulation of c-Jun, Bcl2, and c-Myc. Taken together, our study suggested the oncogenic role of TRAF6 in ESCC, and TRAF6 might be an important therapeutic target for ESCC.

LDHA is necessary for the tumorigenicity of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most common lethal tumors in the world, and the development of new therapeutic targets is needed. Recent studies have shown that aerobic glycolysis, also known as the Warburg effect, mediated the anti-apoptotic effects in cancer cells. Lactate dehydrogenase A (LDHA) which executed the final step of aerobic lactate production has been reported to be involved in the tumor progression. However, the function of LDHA in ESCC has not been investigated. In this study, it was found that LDHA was up-regulated in ESCC clinical samples. Knockdown of the expression of LDHA inhibited cell growth and cell migration in vitro as well as tumorigenesis in vivo. With regard to the molecular mechanism, silencing the expression of LDHA was related to decreased AKT activation and cyclin D1 expression and increased cleavage of PARP and caspase 8. Taken together, our findings suggest that LDHA plays an important role in the progression of ESCC by modulating cell growth, and LDHA might be a potential therapeutic target in ESCC.

Mevalonate pathway is a therapeutic target in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most common lethal tumors in the world. Thus, it is very urgent to develop new therapeutic targets against this disease. The mevalonate (MVA) pathway, paced by its rate-limiting enzyme, hydroxymethylglutaryl coenzyme A reductase, is required for the generation of several fundamental end products including cholesterol and isoprenoids. The function of the MVA pathway in ESCC has not been investigated. In this study, it was found that the MVA pathway was upregulated in ESCC clinical samples. Statin, the inhibitor of the MVA pathway, exerted potent cytotoxicity against human ESCC cells by inhibiting cell growth and proliferation, while it exerted lesser effects on non-tumorigenic SHEE cells. Further study revealed that statin could potently induce cell apoptosis and cell cycle arrest and also dose-dependently inhibit the growth of xenograft tumors in nude mice. With regard to the molecular mechanism, statin treatment was related to decreased extracellular signal-regulated kinase activation and proliferating cell nuclear antigen, cyclin D1 expression, and increased cleavage of poly(ADP-ribose) polymerase. Taken together, our findings suggest that the MVA pathway plays an important role in the progression of ESCC by modulating cell growth and statin might be a potential therapeutic agent in ESCC.

Ground glass opacity resection extent assessment trial (GREAT): A study protocol of multi-institutional, prospective, open-label, randomized phase III trial of minimally invasive segmentectomy versus lobectomy for ground glass opacity (GGO)-containing early-stage invasive lung adenocarcinoma.

Background: With widely use of computed tomography (CT) screening, an increasing number of early-stage lung cancers appearing as ground glass opacity (GGO) have been detected. Therefore, attempts have been made to investigate the feasibility of segmentectomy instead of lobectomy for those patients with GGO. However, the two recently released phase III trials failed to distinguish between GGO-containing lesions from pure solid nodules in the inclusion criteria, and the surgical methods did not distinguish between minimally invasive surgery and open thoracotomy. In addition, total lesion size≤ 2cm was taken as the inclusion criterion, instead of the solid part size recommended in the eighth edition of Union for International Cancer Control/International Association for the Study of Lung Cancer/American Joint Committee on Cancer (UICC/IASLC/AJCC) staging system. Hence, this present trial aims to figure out whether minimally invasive segmentectomy shows superiority in perioperative outcomes and non-inferiority in oncological prognosis over minimally invasive lobectomy among patients with GGO-containing clinical stage T1a-T1b lung invasive adenocarcinoma (IADC). Methods/design: Sample sizes are 1024 patients, who will be randomized into minimally invasive segmentectomy and lobectomy groups . Patients will be collected from 19 hospitals in China. Patients with peripheral mixed ground glass opacity (mGGO) with 0.5cm

Gender differences in empathy, emotional intelligence and problem-solving ability among nursing students: A cross-sectional study.

BACKGROUND: Empathy, emotional intelligence (EI) and problem-solving ability are three important characteristics that influence effective communication in clinical practice. Previous studies have not adequately explored the specific relationships between these three abilities and their gender differences among nursing students. OBJECTIVE: We sought to investigate the current state of emotional intelligence, empathy, and problem-solving ability in nursing students and to identify whether gender differences affect these three characteristics and how gender differences can be used to educate nurses on empathy. DESIGN: We conducted a cross-sectional survey. PARTICIPANTS: A total of 993 nursing students from two grade A tertiary hospitals in Hunan, China participated in this study. METHODS: Data were collected using the Empathy of Clinical Nurse Scale (ENCS), Emotional Intelligence Scale of Clinical Junior Nurses (EIS) and Social Problem-Solving Inventory (SPSI). Data were analyzed using an independent samples t-test, Pearson correlation and hierarchical multiple linear regression. RESULTS: There was no significant difference in the ENCS and SPSI scores between male and female nursing students, but male nursing students had lower EIS scores (P < 0.05). A significant association was found between ENCS, EIS and SPSI on most dimensions among female nursing students, but no significant association was found between ENCS and EIS for total scores among males. We found that problem-solving ability was the most important factor affecting the variation in empathy for both male and female nursing students through hierarchical multiple regression analysis. CONCLUSIONS: Gender differences are reflected not only in the level of emotional intelligence but also in the relationships between emotional intelligence, empathy, and problem-solving ability. Nursing educators should be aware of how gender differences can affect these three traits; this is particularly important for teaching based on students' aptitudes.

Phosphorylation by IKKß Promotes the Degradation of HMGCL via NEDD4 in Lung Cancer.

Inflammation and metabolic reprogramming are hallmarks of cancer. How inflammation regulates cancer metabolism remains poorly understood. In this study, we found that 3-hydroxy-3-methylglutaryl-CoA lyase (HMGCL), the enzyme that catalyzes the catabolism of leucine and promotes the synthesis of ketone bodies, was downregulated in lung cancer. Downregulation of HMGCL was associated with a larger tumor size and a shorter overall survival time. In a functional study, overexpression of HMGCL increased the content of ß-hydroxybutyrate (ß-HB) and inhibited the tumorigenicity of lung cancer cells, and deletion of HMGCL promoted de novo tumorigenesis in KP (KrasG12D;P53f/f) mice. Mechanistically, tumor necrosis factor α (TNFα) treatment decreased the HMGCL protein level, and IKKß interacted with HMGCL and phosphorylated it at Ser258, which destabilized HMGCL. Moreover, NEDD4 was identified as the E3 ligase for HMGCL and promoted its degradation. In addition, mutation of Ser258 to alanine inhibited the ubiquitination of HMGCL by NEDD4 and thus inhibited the anchorage-independent growth of lung cancer cells more efficiently than did wild-type HMGCL. In summary, this study demonstrated a link between TNFα-mediated inflammation and cancer metabolism.

Nicotinamide adenine dinucleotide kinase promotes lymph node metastasis of NSCLC via activating ID1 expression through BMP pathway.

Metastasis is a significant cause of high mortality in lung cancer. Lymph node (LN) metastasis is the most common metastatic pathway in non-small cell lung cancer and the most crucial factor affecting the prognosis of NSCLC. Nevertheless, the molecular mechanism underlying metastasis is unknown. We demonstrated that higher NADK expression suggests worsened survival prognosis, and NADK expression positively correlates with the lymph node metastasis rate and TNM and AJCC stages in NSCLC patients. Moreover, patients with LN metastasis show higher NADK expression than those without LN metastasis. NADK can promote NSCLC progression by enhancing the migration, invasion, lymph node metastasis and growth of NSCLC cells. Mechanistically, NADK inhibits the ubiquitination and degradation of BMPR1A by interacting with Smurf1, further activating the BMPs signalling pathway and promoting ID1 transcription. In conclusion, NADK may be a potential diagnostic indicator and a novel therapeutic target for metastatic NSCLC.

Hydrogen saline is protective for acute lung ischaemia/reperfusion injuries in rats.

BACKGROUND: Protective effects of saturated hydrogen (H(2)) saline on cardiac ischaemia-reperfusion (I/R) injury have been demonstrated previously. This study was designed to show that hydrogen-rich saline is protective in preventing lung I/R injury in rats. METHODS: Adult male Sprague-Dawley rats underwent 45 min occlusion of the right lung roots and 120 min reperfusion. Rats were divided randomly into three groups: sham-operated control group, I/R plus saline treatment, and I/R plus hydrogen-rich saline treatment (0.6 mmol/L, 0.5 ml/kg/d). Three days of intraperitoneal injection of hydrogen-rich saline before the reperfusion combined with immediate administration of hydrogen-rich saline after the reperfusion were performed. Following reperfusion, the lung tissue and the pulmonary artery was immediately obtained and the W/D ratio, pulmonary artery contraction and relaxation ability, H-E staining, TUNEL staining, caspase-3, MDA, 8-OHdG content and measurement of such biomarkers as WBC, CRP were measured or carried out. RESULTS: Hydrogen saline significantly protected vasoactivity of the pulmonary artery, reduced pulmonary oedema, decreased lung malondialdehyde (MDA), 8-OHdG concentration, alleviated lung epithelial cell apoptosis and lowered the level of such biomarkers as WBC, CRP, ALT and TBiL. CONCLUSIONS: It is concluded that hydrogen-rich saline is a novel, simple, safe and effective method to attenuate pulmonary I/R injury.