Remodelin delays non-small cell lung cancer progression by inhibiting NAT10 via the EMT pathway.

BACKGROUND: Lung cancer remains the foremost reason of cancer-related mortality, with invasion and metastasis profoundly influencing patient prognosis. N-acetyltransferase 10 (NAT10) catalyzes the exclusive N (4)-acetylcytidine (ac4C) modification in eukaryotic RNA. NAT10 dysregulation is linked to various diseases, yet its role in non-small cell lung cancer (NSCLC) invasion and metastasis remains unclear. Our study delves into the clinical significance and functional aspects of NAT10 in NSCLC. METHODS: We investigated NAT10's clinical relevance using The Cancer Genome Atlas (TCGA) and a group of 98 NSCLC patients. Employing WB, qRT-PCR, and IHC analyses, we assessed NAT10 expression in NSCLC tissues, bronchial epithelial cells (BECs), NSCLC cell lines, and mouse xenografts. Further, knockdown and overexpression techniques (siRNA, shRNA, and plasmid) were employed to evaluate NAT10's effects. A series of assays were carried out, including CCK-8, colony formation, wound healing, and transwell assays, to elucidate NAT10's role in proliferation, invasion, and metastasis. Additionally, we utilized lung cancer patient-derived 3D organoids, mouse xenograft models, and Remodelin (NAT10 inhibitor) to corroborate these findings. RESULTS: Our investigations revealed high NAT10 expression in NSCLC tissues, cell lines and mouse xenograft models. High NAT10 level correlated with advanced T stage, lymph node metastasis and poor overall survive. NAT10 knockdown curtailed proliferation, invasion, and migration, whereas NAT10 overexpression yielded contrary effects. Furthermore, diminished NAT10 levels correlated with increased E-cadherin level whereas decreased N-cadherin and vimentin expressions, while heightened NAT10 expression displayed contrasting results. Notably, Remodelin efficiently attenuated NSCLC proliferation, invasion, and migration by inhibiting NAT10 through the epithelial-mesenchymal transition (EMT) pathway. CONCLUSIONS: Our data underscore NAT10 as a potential therapeutic target for NSCLC, presenting avenues for targeted intervention against lung cancer through NAT10 inhibition.

Evaluation of drug resistance for EGFR-TKIs in lung cancer via multicellular lung-on-a-chip.

Drug resistance to irreversible epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is a primary factor affecting their therapeutic efficacy in human non-small cell lung cancer (NSCLC). NSCLC cells can undergo epithelial-mesenchymal transition (EMT) induced by many factors in the tumour microenvironment (TME), which plays a crucial role in tumour drug resistance. In this study, a multicellular lung-on-a-chip that can realise the cell co-culture of the human non-small cell lung cancer cell line HCC827, human foetal lung fibroblasts (HFL-1), and human umbilical vein endothelial cells (HUVECs) is prepared. The TME was simulated on the chip combined with perfusion and other factors, and the drug evaluation of osimertinib was performed to explore the drug resistance mechanism of EGFR-TKIs. In the early stages, a two-dimensional static cell co-culture was achieved by microchip, and the results showed that HFL-1 cells could be transformed into cancer-associated fibroblasts (CAFs), and HCC827 cells could undergo EMT, both of which were mediated by Interleukin-6 (IL-6). Vimentin (VIM) and Alpha Skeletal Muscle Actin (a-SMA) expression of HFL-1 was upregulated, whereas E-cadherin (E-cad) expression of HCC827 was down-regulated. Further, N-cadherin (N-cad) expression of HCC827 was upregulated. In both the static cell co-culture and multicellular lung-on-a-chip, HCC827 cells with CAFs co-culture or IL-6 treatment developed resistance to osimertinib. Further use of the IL-6 antibody inhibitor tocilizumab could reverse EGFR-TKI resistance to a certain extent. Combination therapy with tocilizumab and EGFR-TKIs may provide a novel therapeutic strategy for overcoming EGFR-TKI resistance caused by EMT in NSCLC. Furthermore, the lung-on-a-chip can simulate complex TME and can be used for evaluating tumour resistance and exploring mechanisms, with the potential to become an important tool for personalised diagnosis, treatment, and biomedical research.

The alterations of cardiac function during venovenous artificial placenta support in fetal goats.

INTRODUCTION: Venovenous artificial placenta (VVAP) may mimic the intrauterine environment for maintaining fetal circulation. However, changes in ventricular function in fetal goats undergoing VVAP support remain unclear. METHODS: Pump-assisted VVAPs were established in five fetal goats for 9 h. The myocardial performance index (Tei index), cardiac output (CO), and blood biochemical parameters were measured during VVAP support. RESULTS: An increasing trend of the right ventricular (RV) Tei index was seen during VVAP support (p for trend < 0.01). The right ventricular cardiac output (RVCO) increased after the initiation of VVAP, while a significant trend of reduction was observed after 3 h (p for trend = 0.03). During VVAP support, we observed remarkable elevations of plasma cTnI and arterial lactic acid, which were positively correlated with the RV Tei index, but not the left ventricular (LV) Tei index, LVCO, and RVCO. CONCLUSIONS: The RVCO increases initially while a tendency of decrease could be observed during VVAP support. Special attention should be paid to right ventricular dysfunction during VVAP support.

Advanced lung organoids and lung-on-a-chip for cancer research and drug evaluation: a review.

Lung cancer has become the primary cause of cancer-related deaths because of its high recurrence rate, ability to metastasise easily, and propensity to develop drug resistance. The wide-ranging heterogeneity of lung cancer subtypes increases the complexity of developing effective therapeutic interventions. Therefore, personalised diagnostic and treatment strategies are required to guide clinical practice. The advent of innovative three-dimensional (3D) culture systems such as organoid and organ-on-a-chip models provides opportunities to address these challenges and revolutionise lung cancer research and drug evaluation. In this review, we introduce the advancements in lung-related 3D culture systems, with a particular focus on lung organoids and lung-on-a-chip, and their latest contributions to lung cancer research and drug evaluation. These developments include various aspects, from authentic simulations and mechanistic enquiries into lung cancer to assessing chemotherapeutic agents and targeted therapeutic interventions. The new 3D culture system can mimic the pathological and physiological microenvironment of the lung, enabling it to supplement or replace existing two-dimensional culture models and animal experimental models and realize the potential for personalised lung cancer treatment.

The association between quality of life and subjective wellbeing among older adults based on canonical correlation analysis.

Introduction: The study explored the relationship between subjective well-being and the quality of life among older adults. It highlights the importance of understanding how these factors are interconnected in the context of an aging population. Methods: Descriptive statistics were used to analyze the scores of general demographic characteristics, subjective wellbeing and quality of life. Simple correlation analysis and canonical correlation analysis were employed to analyze the relationship between subjective wellbeing and quality of life among older adults. Results: Data from 892 older adults were collected. Canonical correlation analysis revealed four pairs of canonical variables, with the first four pairs of canonical correlation coefficients all being statistically significant (0.695, 0.179, 0.147, 0.121) (p < 0.05), and the first pair of canonical variables explaining 93.03% of the information content. From the canonical loading coefficients, Vitality and mental health contributed the most to the quality of life (U1) canonical variable. The canonical variable V1, which corresponded to subjective wellbeing, was reflected by a combination of positive affect, negative affect, positive experience and negative experience. X1 (physical functioning), X2 (role-physical), X3 (bodily pain), X4 (general health), X5 (vitality), X6 (social functioning), X7 (role-emotional) and X8 (mental health) were positively correlated with Y1 (positive affect) and Y3 (positive experience), negatively correlated with Y2 (negative affect) and Y4 (negative experience). Cross-loadings revealed that physical functioning, bodily pain, general health, vitality, social functioning and mental health were the main factors reflecting the subjective wellbeing of older adults. Discussion: As quality of life among older adults was highly correlated with subjective wellbeing, appropriate measures should be taken to account for individual characteristics of older adults, and various factors should be integrated to improve their subjective wellbeing.

Preparation of Elastic Macroporous Graphene Aerogel Based on Pickering Emulsion Method and Combination with ETPU for High Performance Piezoresistive Sensors.

High-performance pressure sensors provide the necessary conditions for smart shoe applications. In this paper, the elastic Macroporous Graphene Aerogel (MGA) was synthesized via the modified Hummers' method, and it was further combined with Expanded-Thermoplastic polyurethane (ETPU) particles to assemble MGA-ETPU flexible sensors. The MGA-ETPU has a low apparent density (3.02 mg/cm3), high conductivity (0.024 S/cm) and fast response time (50 ms). The MGA-ETPU has a large linear sensing range (0-10 kPa) and consists of two linear regions: the low-pressure region (0 to 8 kPa) and the high-pressure region (8 to 10 kPa), with sensitivities of 0.08 kPa-1, and 0.246 kPa-1, respectively. Mechanical test results show that the MGA-ETPU sensor showed 19% reduction in maximum stress after 400 loading-unloading compression cycles at 40% strain. Electrical performance tests showed that the resistance of MGA-ETPU sensor decreased by 12.5% when subjected to sudden compression at 82% strain and returned to its original state within 0.05 s. Compared to existing flexible sensors, the MGA-ETPU sensors offer excellent performance and several distinct advantages, including ease of fabrication, high sensitivity, fast response time, and good flexibility. These remarkable features make them ideally suited as flexible pressure sensors for smart shoes.

Integrated analysis of single-cell and Bulk RNA sequencing reveals a malignancy-related signature in lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD), the most common histotype of lung cancer, may have variable prognosis due to molecular variations. The research strived to establish a prognostic model based on malignancy-related risk score (MRRS) in LUAD. Methods: We applied the single-cell RNA sequencing (scRNA-seq) data from Tumor Immune Single Cell Hub database to recognize malignancy-related geneset. Meanwhile, we extracted RNA-seq data from The Cancer Genome Atlas database. The GSE68465 and GSE72094 datasets from the Gene Expression Omnibus database were downloaded to validate the prognostic signature. Random survival forest analysis screened MRRS with prognostic significance. Multivariate Cox analysis was leveraged to establish the MRRS. Furthermore, the biological functions, gene mutations, and immune landscape were investigated to uncover the underlying mechanisms of the malignancy-related signature. In addition, we used qRT-PCR to explore the expression profile of MRRS-constructed genes in LUAD cells. Results: The scRNA-seq analysis revealed the markers genes of malignant celltype. The MRRS composed of 7 malignancy-related genes was constructed for each patient, which was shown to be an independent prognostic factor. The results of the GSE68465 and GSE72094 datasets validated MRRS's prognostic value. Further analysis demonstrated that MRRS was involved in oncogenic pathways, genetic mutations, and immune functions. Moreover, the results of qRT-PCR were consistent with bioinformatics analysis. Conclusion: Our research recognized a novel malignancy-related signature for predicting the prognosis of LUAD patients and highlighted a promising prognostic and treatment marker for LUAD patients.

Exploration of the methods of establishing the minimum clinical important difference based on anchors and their applications in the quality of life measurement scale QLICP-BR (V2.0) for breast cancer.

Objective: The measurement of the quality of life (QOL) in patients with breast cancer can evaluate the therapeutic effects of medical treatments and help to provide reference for clinical decisions. The minimum clinically important difference (MCID) can be better used in clinical interpretation than the traditional statistical significance. Based on the anchors, a variety of ways including traditional and updated anchor-based methods were used to explore most suitable MCID, so that to find better interpretation on scores of the scale QLICP-BR(V2.0) (Quality of Life Instruments for Cancer Patients-Breast cancer). Methods: According to the investigation data of breast cancer patients before and after treatment, the most relevant indicators in various domains of QLICP-BR (V2.0) was found as an anchor to statistically analyze the value of MCID, and three analysis methods of anchors were used: Traditional anchor-based method, ROC curve method, multiple linear regression model analysis. Anchors are divided into four standards according to the degree of change in the treatment effect: one grade difference (Standard A), at least one grade difference (Standard B), one grade better (Standard C), better (Standard D). The final MCID value is selected from different statistical methods and classification standards that are most suitable for clinicians to use. Results: Using Q29 of the EORTC QLQ-C30 as an anchor has the highest correlation with each domain of QLICP. The order of magnitude of MCID values among the four standard groups is: standard A< Standard C< Standard B< Standard D. The MCID value obtained by the ROC curve method is the most stable and is least affected by the sample size, and the MCID value obtained by the multiple linear regression model is the least. After comparisons and discussions, Standard C in the multiple linear regression model is used to determine the final MCID, which is the closest to other methods. After integer the MCID values of Physical domain (PHD), Psychological domain (PSD), Social domain (SOD), Common symptoms and side effect domain (SSD), Core/general module (CGD), Specific domain (SPD), Total score(TOT) can be taken as 15,10, 10, 11, 10, 9 and 9, respectively. Conclusion: In the evaluation of the QOL of breast cancer patients, although the results of MCID values produced by different methods are different, the results are relatively close. The anchor-based methods make the results of MCID more clinically interpretable by introducing clinical variables, and clinicians and researchers can choose the appropriate method according to the research purpose.

Biomimetic lung-on-a-chip to model virus infection and drug evaluation.

Viral infectious diseases remain a global public health problem. The rapid and widespread spread of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV­2) has had a severe impact on the global economy and human activities, highlighting the vulnerability of humans to viral infectious diseases and the urgent need to develop new technologies and effective treatments. Organ-on-a-chip is an emerging technology for constructing the physiological and pathological microenvironment of human organs in vitro and has the advantages of portability, high throughput, low cost, and accurate simulation of the in vivo microenvironment. Indeed, organ-on-a-chip provides a low-cost alternative for investigating human organ physiology, organ diseases, toxicology, and drug efficacy. The lung is a main target organ of viral infection, and lung pathophysiology must be assessed after viral infection and treatment with antiviral drugs. This review introduces the construction of lung-on-a-chip and its related pathophysiological models, focusing on the in vitro simulation of viral infection and evaluation of antiviral drugs, providing a developmental direction for research and treatment of viral diseases.

Advanced aqueous sodium-ion capacitors based on Ni0.25Mn0.75O nanoparticles encapsulated in electrospinning carbon nanofibers.

Manganese oxides are promising cathode material candidates with appropriate positive potential windows for low-cost and safe aqueous sodium-ion capacitors (ASICs). However, their low electrical conductivity issue and the lack of advanced binder-free manganese oxide-based electrodes severely restrict their practical capacitance and application in flexible ASICs. Here, Ni0.25Mn0.75O (NMO) nanoparticles uniformly encapsulated in carbon nanofiber films with excellent flexibility are fabricated by electrospinning and subsequent carbonization. The uniformly amorphous carbon layer enhances the conductivity, avoids dissolution and alleviates the volume or stress change of NMO during ion intercalation or mechanical deformation. More importantly, compared with the flexible electrodes prepared by traditional methods, electrospinning materials can be directly used as binder-free electrodes, which can effectively simplify the process and improve the energy density. Finally, a 2.4 V flexible quasi-solid-state ASIC device is integrated, which exhibits a high energy density of 5.95 mWh cm-3, a high power density of 670 mW cm-3 and an outstanding stability of 1000 cycles. This work offers an effective materials engineering strategy for high-performance binder-free NMO-based cathodes and advanced flexible ASICs.

Confirmation of lung adenocarcinoma as the primary cancer with detection of EML4-ALK rearrangement using next-generation sequencing: a case study.

We report a female patient, who presented as a carcinoma of unknown primary site with multiple tumors in breast, lung, stomach, and ovary, was confirmed to be lung adenocarcinoma as primary cancer through detecting EML4-ALK rearrangement by the next generation sequencing (NGS). The patient was treated with crizotinib and resulted in significant regression of the primary and metastatic tumors, but resistance to crizotinib was developed 5 months after the treatment. Targeted therapy was, therefore, switched to alectinib, one of the second-generation of anaplastic lymphoma kinase (ALK) inhibitors, with excellent therapeutic response till November 16th, 2021. This study suggested that NGS be recommended to detect ALK rearrangement in the patients with carcinoma of unknown primary site, and that resistance to targeted therapy with ALK inhibitors should be considered for personalized precision medicine.

Exploratory Evaluation of EGFR-Targeted Anti-Tumor Drugs for Lung Cancer Based on Lung-on-a-Chip.

In this study, we used three-dimensional (3D) printing to prepare a template of a microfluidic chip from which a polydimethylsiloxane (PDMS)lung chip was successfully constructed. The upper and lower channels of the chip are separated by a microporous membrane. The upper channel is seeded with lung cancer cells, and the lower channel is seeded with vascular endothelial cells and continuously perfused with cell culture medium. This lung chip can simulate the microenvironment of lung tissue and realize the coculture of two kinds of cells at different levels. We used a two-dimensional (2D) well plate and a 3D lung chip to evaluate the effects of different EGFR-targeting drugs (gefitinib, afatinib, and osimertinib) on tumor cells. The 3D lung chip was superior to the 2D well plate at evaluating the effect of drugs on the NCI-H650, and the results were more consistent with existing clinical data. For primary tumor cells, 3D lung chips have more advantages because they simulate conditions that are more similar to the physiological cell microenvironment. The evaluation of EGFR-targeted drugs on lung chips is of great significance for personalized diagnosis and treatment and pharmacodynamic evaluation.

Rare ectopic thyroid tissue as multiple bilateral pulmonary nodules: a case report and literature review.

BACKGROUND: The prevalence of ectopic thyroid tissue is 1 in every 100,000 to 300,000 persons in the general population, and ectopic thyroid tissue in the bilateral lung lobes is even rarer. Due to its rarity, there is no definitive or standard guidance on the diagnosis and treatment of ectopic thyroid tissue presenting as multiple bilateral pulmonary nodules. CASE PRESENTATION: A 56-year-old woman presented with multiple bilateral pulmonary nodules, and the patient had a history of hyperthyroidism but had no symptoms of ectopic thyroid tissue. Computed tomography (CT) demonstrated multiple solid nodules in both lungs, and the largest nodule (sized 15 × 14 mm) was located in segment 5 of the upper left lung. The initial diagnosis based on imaging was metastatic malignancies. Positron emission tomography-computed tomography (PET-CT) showed multiple bilateral intrapulmonary nodules that had slightly increased metabolism (SUVmax 1.7). The largest pulmonary nodule and another nodule in the left lung were resected by video-assisted thoracoscopy surgery (VATS). The pathological and immunohistochemical (IHC) examinations confirmed a diagnosis of ectopic thyroid tissue. No postoperative adjuvant therapy was given, and the patient was discharged 3 days after the operation and had regular follow-up examinations. CONCLUSION: The diagnosis of ectopic thyroid tissue in the bilateral lung lobes is extremely difficult and should be considered carefully. PET-CT and surgical resection of intrapulmonary nodules are alternatives for clinicians in diagnosing ectopic thyroid tissue. Regular postoperative follow-up is needed.

Bone marrow mesenchymal stem cells-derived exosomes containing miR-539-5p inhibit pyroptosis through NLRP3/caspase-1 signalling to alleviate inflammatory bowel disease.

BACKGROUND: Exosomes derived from bone mesenchymal stem cells (BMSCs) are potential candidates for inflammatory bowel disease (IBD) treatment. The present study investigated the therapeutic effect and potential mechanism of BMSCs-derived exosomes on pyroptosis in IBD. METHODS: We induced IBD in mice and cell models through dextran sulfate sodium (DSS) and LPS, respectively. The mRNA and protein expression levels were assessed by qRT-PCR, Western blotting, IF and IHC. The concentrations of IL-1ß, IL-18 and TNFα were assessed using ELISA. ROS levels were determined using DCFH-DA staining. Cell proliferation of mIECs was analysed using an MTT assay. In addition, a flow cytometry assay was performed to detect pyroptosis. Finally, the binding relationship between miR-539-5p and NLRP3 was verified by a dual luciferase reporter gene assay. RESULTS: Our results revealed that intraperitoneal injection of BMSCs-derived exosomes inhibited DSS-induced pyroptosis as well as IBD symptoms in mice. In addition, BMSCs-derived exosome treatment suppressed pyroptosis, ROS levels and the concentrations of proinflammatory cytokines (IL-1ß, IL-18 and TNFα) in LPS-treated mIECs in a miR-539-5p-dependent manner. Further research found that miR-539-5p suppressed NLRP3 expression in mIECs by directly targeting NLRP3. As expected, pyroptosis in LPS-treated mIECs was significantly reduced by NLRP3 knockdown. In addition, NLRP3 silencing restored the inhibitory effect of exosomes derived from BMSCs transfected with miR-539-5p inhibitor on pyroptosis in LPS-treated mIECs. CONCLUSION: The present study demonstrated that BMSCs-derived exosomal miR-539-5p suppresses pyroptosis through NLRP3/caspase-1 signalling to inhibit IBD progression.

Canonical correlation analysis of factors that influence quality of life among patients with chronic obstructive pulmonary disease based on QLICD-COPD (V2.0).

BACKGROUND: The Quality of Life Instrument for Chronic Diseases (QLICD)-COPD (V2.0) was designed to assess the health condition of patients with chronic obstructive pulmonary disease (COPD). The objective of this study was to evaluate the quality of life (QOL) of patients, the influential clinical factors and the relationships between QOL and clinical objective indicators. METHODS: Two hundred and sixty-one inpatients with COPD in the acute exacerbation stage were evaluated using the QLICD-COPD (V2.0) and data on clinical objective indicators were collected. The relationships between QOL and the clinical objective indicators were determined using canonical correlation analysis. RESULTS: The standardised scores for the patients in four domains, namely, physical function, psychological function, social function and a disease-specific module, were 49.00±12.91, 59.89±13.51, 68.59±11.94 and 51.84±13.58, respectively. The total score for the QOL of patients was 57.17±10.26. Two pairs of canonical variables were statistically significant (r1=0.35, p<0.0001; r2=0.26, p<0.05). These variables accounted for 45.8% and 33.8% of the variance, respectively. The levels of total protein, albumin, serum sodium and alkaline phosphatase and the percentages of neutrophils and lymphocytes were correlated with the QOL, with correlation coefficients ranging from -0.435 to 0.675. CONCLUSION: Clinicians should pay close attention to the levels of total protein, albumin, serum sodium and alkaline phosphatase and the percentages of neutrophils and lymphocytes to improve the QOL of patients.

Establishing Minimal Clinically Important Differences for the Quality of Life Instrument in Patients With Breast Cancer QLICP-BR (V2.0) Based on Anchor-Based and Distribution-Based Methods.

Objective: To determine the minimal clinically important differences (MCIDs) for the breast cancer scale QLICP-BR (V2.0) among the Quality of Life Instruments system for cancer patients (QLICP), which consist of the general module of 32 items classifying into 4 domains and the specific module of 10 items. Methods: According to the scoring rule of QLICP-BR (V2.0), the scores of each domain and the overall scale were calculated. The MCIDs of this scale were established by anchor-based and distribution-based methods. The anchor method used the Q29 item in the EORTC QLQ-C30 scale as anchors and defined the treatment effectiveness of the anchor-based method using criteria A (one level improvement after treatment) and B (at least one level improvement after treatment), while methods of effect size (ES), standard error of measurement (SEM), and reliability change index (RCI) were used in distribution-based methods. Results: Using the anchor-based method, according to standard A, the MCIDs of the physical domain (PHD), psychological domain (PSD), social domain (SOD), common symptoms and side effect domain (SSD), core/general module (CGD), specific domain (SPD), and the total score (TOT) were 16.24, 11.37, 11.31, 12.07, 11.49, 10.69, and 11.23 respectively; according to standard B, the MCIDs of PHD, PSD, SOD, SSD, CGD, SPD, and TOT were 18.88, 15.14, 14.10, 14.50, 13.93, 12.17, and 14.23 respectively. In the distribution-based MCID study, when ES = 0.8, the MCID values of each domain and the total score of the scale were 9.14, 10.34, 8.34, 10.54, 6.79, 9.73, and 6.96 respectively. The MCIDs calculated when a SEM of 1.96 was used as the intermediary index were 8.38, 11.04, 8.67, 10.00, 7.44, 9.83, and 7.81. The MCIDs calculated when a RCI of 1.96 was used as the intermediary index were 11.84, 15.61, 12.27, 14.14, 10.52, 13.90, and 11.05. Additionally, the MCID value calculated by the two standards of the anchor method was similar to 0.8 ES, 1.96 SEM, and 1.96 RCI. Conclusion: Using the anchor-based method, 0.8ES, 1.96SEM, and 1.96RCI have a better effect on the minimal clinically important difference of breast cancer scale and were recommended to be the preferred methods for establishing MCID.

Development and validation of the psoriasis scale among the system of quality of life instruments for chronic diseases QLICD-PS (V2.0).

BACKGROUND AND PURPOSE: Psoriasis (PS) is difficult to cure with a high incidence. Therefore, the quality of life (QOL) of people with Psoriasis has caused widespread concern. Universal scales respond poorly to subtle changes caused by specific diseases, which makes it challenging to fully understand the impact of QOL in patients with psoriasis. In view of the deficiencies of the universal scale and the lack of a specific scale suitable for Chinese cultural background, this study aims to develop the psoriasis scale among the system of QOL instruments for chronic diseases QLICD-PS (V2.0). METHODS: The scale QLICD-PS (V2.0) was developed based on the procedural decision-making approach and the experience of establishing scales at home and abroad. 122 patients with psoriasis were participated in measuring QOL 3 times before and after treatments. The reliability was assessed by test-retest reliability (Pearson's correlation coefficients) and also internal consistency (Cronbach's alpha coefficients). Qualitative analysis was adopted to evaluate content validity; item-domain correlation analysis, multi-dimensional scaling analysis, and factor analysis were adopted to evaluate the construct validity; the SF-36 scale was used as the criterion to evaluate the criterion-related validity due to lack of gold standard. Paired t tests were performed to evaluate the responsiveness on each domain/facet as well as the total of the scale, with Standardized Response Mean (SRM) being calculated. RESULTS: The QLICD-PS was composed of the general module including 3 domains (28 items) and the psoriasis specific module (13 items). The Cronbach's α of the specific module, the general module and the total scale of the QLICD-PS was 0.78, 0.87 and 0.74 respectively, the split-half reliability of the specific module, the general module and the total scale was 0.81, 0.91 and 0.81, respectively, both indicating high reliability. Correlation and factor analysis confirmed good construct validity and criterion-related validity. After treatments, the score changes in the total scale were statistically significant with SRM being 0.5, showing moderate responsiveness. CONCLUSION: As the first psoriasis-specific QOL scale developed by the modular approach in Chinese, the QLICD-PS showed good reliability, validity and responsiveness, and could be used to measure the QOL of Patients with psoriasis specifically and sufficiently.

microRNA-130b-3p Contained in MSC-Derived EVs Promotes Lung Cancer Progression by Regulating the FOXO3/NFE2L2/TXNRD1 Axis.

This study aimed to explore the molecular mechanism by which mesenchymal stem cells (MSCs) mediate lung cancer progression. Extracellular vesicles (EVs) were isolated from transfected or untransfected MSCs, and were co-cultured with lung cancer cells with/without microRNA-130b-3p (miR-130b-3p) inhibitor, mimic, overexpression plasmids of FOXO3/NFE2L2, or shRNAs. CCK-8 assay, colony formation, transwell assay, and flow cytometry were carried out to determine the biological functioning of lung cancer cells. Furthermore, FOXO3, Keap1, NFE2L2, and TXNRD1 expression was determined by qRT-PCR and western blot analysis. A tumor xenograft mouse model was used to determine role of EVs-miR-130b-3p and its target FOXO3 in lung cancer progression in vivo. miR-130b-3p was highly expressed in lung cancer tissues and MSC-derived EVs. Moreover, the MSC-derived EVs transferred miR-130b-3p to lung cancer cells to promote cell proliferation, migration, and invasion while repress cell apoptosis. miR-130b-3p directly targeted FOXO3, and FOXO3 elevated Keap1 expression to downregulate NFE2L2, thus inhibiting TXNRD1. FOXO3 overexpression or silencing of NFE2L2 or TXNRD1 diminished lung cancer cell proliferation, invasion, and migration but enhanced apoptosis. EV-delivered miR-130b-3p or FOXO3 silencing promoted lung cancer progression in vivo. In summary, MSC-derived EVs with upregulated miR-130b-3p suppressed FOXO3 to block the NFE2L2/TXNRD1 pathway, thus playing an oncogenic role in lung cancer progression.

Myeloid and plasmacytoid dendritic cell combined vaccines loaded with heat-treated tumor cell lysates enhance antitumor activity in murine lung cancer.

The present study aimed to investigate the efficacy of a myeloid dendritic cell (mDCs) and plasmacytoid (p)DC combined vaccine loaded with heat-treated cancer cell lysates against lung cancer cells. The mDCs and pDCs were selected using magnetic bead sorting. Antigen loading was performed by adding heat-treated Lewis lung cancer cell lysates to mDC, pDC or mDC+pDC (1:1). Surface expression of CD80, CD86, CD40 and major histocompatibility complex (MHC)-II molecules were determined using flow cytometry, and the secretion of cytokines IL-12, IL-6 and TNF-α were assessed using ELISA assays. The effect of the mDC and pDC vaccine on cytotoxic T lymphocytes (CTLs) against tumor cells was investigated. Tumor-bearing nude mice were intravenously injected with the mDC and pDC combined vaccine. Tumor tissues were collected for hematoxylin and eosin and TUNEL staining. Loading with tumor cell lysate significantly upregulated the surface expression of costimulatory molecules MHC-II on DCs and enhanced secretions of IL-6, IL-12 and TNF-α by DCs. In addition, the tumor cell lysate-loaded mDC and pDC combined vaccine significantly promoted lymphocyte proliferation and enhanced CTL-mediated cytotoxicity against Lewis lung cancer cells compared with mDC or pDC treatment alone. Furthermore, intravenous injection of the mDC and pDC combined vaccine into tumor-bearing nude mice significantly inhibited subcutaneous tumor growth and induced necrosis and apoptosis within the tumor tissue. Overall, the pDC and mDC combination vaccine loaded with heat-treated Lewis lung cancer cell lysate had a synergistic effect on the induction of T lymphocyte proliferation and antitumor efficacy, which may be associated with the upregulation of co-stimulatory molecules and cytokine secretions.

Undergraduate students' norms for the Chinese version of the symptom check-List-90-R (SCL-90-R).

BACKGROUND: Despite widespread application of the Symptom Check-List-90-R (SCL-90-R) for Chinese undergraduate students, there are no appropriate norms for them. The aim of this study is to provide norms for the Chinese version of the tool for undergraduate students using a large and representative sample. METHODS: Four thousand eight hundred sixty students completed the scale of SCL-90. The mean scores obtained in the present study were compared with mean scores from previous normative samples. RESULTS: The mean scores for nine subscales of the SCL-90-R ranged from (1.36 ± 0.46) ~ (1.77 ± 0.63) and the mean (standard deviation) Global Severity Index (GSI) was 1.50 (0.49). Relative to previous normative studies, the findings suggested that Chinese undergraduate students' self-reported mental health symptoms decreased in interpersonal sensitivity, depression, hostility, and paranoid ideation subscales. CONCLUSION: It is necessary to revise the norms of the Chinese version of the SCL-90-R for undergraduate students.