A Case of Follicular Atresia Triad Combined with Necrotising Fasciitis and Squamous Carcinoma of the Lower Limbs.

Follicular atresia triad, also known as paradoxical acne (FOT), is a rare and serious clinical syndrome in dermatology, mainly manifested by coalescing acne, purulent perifolliculitis of the head, and suppurative sweating inflammation, and FOT combined with necrotising fasciitis of the lower limbs and squamous cell carcinoma is rare both at home and abroad. In this article, we share the clinical data and treatment of a patient with follicular atresia triad and necrotising fasciitis and squamous cell carcinoma of the left lower limb for your reference.

Response Surface Methodology to Explore the Influence Mechanism of Fiber Diameter in a New Multi-Needle Electrospinning Spinneret.

Multi-needle electrospinning is an efficient method for producing nanofiber membranes. However, fluctuations in the fluid flow rate during the process affect membrane quality and cause instability, an issue that remains unresolved. To address this, a multi-stage flow runner spinneret needs to be developed for large-scale nanofiber membrane production. This paper uses COMSOL finite element software to simulate polymer flow in the spinneret runner. From this, the velocity field distribution and velocity instability coefficient were obtained, providing theoretical guidance for optimal spinneret design. In addition, response surface analysis (RSM) was used to experimentally explore the process parameters, and then residual probability plots were used for reliability verification to evaluate the effect of each process parameter on fiber diameter. These process parameters can guide the controlled production of nanofibers during multi-needle electrospinning.

Intradermal Injection in Balding Region Versus Intramuscular Injection in Surrounding Muscles: A Split-Scalp, Randomized Trial on BoNT for Androgenetic Alopecia.

INTRODUCTION: Recent advancements in androgenetic alopecia (AGA) treatment have highlighted the efficacy of botulinum toxin (BoNT). However, inconsistencies in injection sites and depths warrant attention. It remains unclear which injection strategy is most beneficial for patients. METHODS: This split-scalp randomized controlled trial divided each enrolled participant's scalp along the midline: one side was randomized to receive intramuscular BoNT injections in the surrounding muscles, while the other side received intradermal BoNT injections directly into the balding areas. This study evaluated the impact of treatment on hair density and diameter through trichoscopic examinations conducted at baseline and 12 weeks post treatment. Additionally, assessments of pain and overall safety were integrated into the study protocol. RESULTS: Twenty-nine patients completed the study, with significant improvements in hair density observed in the intramuscular injection group compared to the intradermal group (p < 0.001). Both groups exhibited increases in hair diameter, but no significant difference was found between the two methods (p = 0.433). Pain evaluation revealed that intradermal injections in balding areas were more painful than intramuscular injections (p = 0.036), with no severe adverse reactions reported except for a single case of alopecia areata following injection. CONCLUSION: Our research revealed that both BoNT injection strategies enhanced hair diameter 12 weeks post-treatment, with intramuscular injections significantly improving hair density more effectively. Despite the promising outcomes, the variability in patient responses underscores the necessity for personalized approaches and further research to refine injection protocols for optimized efficacy and safety. TRIAL REGISTRATION NUMBER: ChiCTR2400080190.

Tobacco control knowledge and beliefs among healthcare workers in respiratory departments in Fujian Province, China: A cross-sectional study.

INTRODUCTION: Smoking prevalence is high in China, and healthcare workers are important for tobacco control. This study aimed to determine the smoking status, cognition of tobacco hazards, and smoking cessation-related knowledge among respiratory healthcare workers, and to explore their ability to provide smoking cessation assistance. METHODS: A cross-sectional study was conducted in 2021 among 1028 respiratory healthcare workers from 89 hospitals in Fujian Province, China. A self-designed electronic questionnaire was used to collect data on smoking status, knowledge of smoking hazards, and smoking cessation knowledge. Descriptive statistics were calculated for all questions. Logistic regression analysis was used to explore the relationship between awareness of the tobacco control goals of Healthy China 2030 and demographic characteristics. RESULTS: Among the healthcare workers surveyed, 3.4% were smokers, all of whom were male. Most respondents (99.4%) were aware of smoking as a cause of lung cancer, but awareness of smoking as a cause of non-respiratory cancer was lower. The awareness rate of smoking cessation support was high (>90%), but only 40.0% of participants were aware of the Healthy China 2030 tobacco control targets. Male (HR=2.16; 95% CI: 1.69-2.80) and participation in the cessation clinic (HR=1.47; 95% CI: 1.10-1.96) were associated with higher awareness of the targets. CONCLUSIONS: Respiratory healthcare workers in Fujian Province demonstrated a high level of awareness regarding behavioral and pharmacotherapy support for smoking cessation. In order to enable healthcare workers to play a more active role in tobacco control, there is a need to increase public awareness of smoking cessation services in Fujian Province.

Predictive Model of CK7 Expression in Patients With Clear Cell Renal Cell Carcinoma by Combined Multimodal Ultrasound Diagnostic Techniques: A Retrospective Study.

OBJECTIVE: The aim of the work described here was to develop and validate a predictive model for cytokeratin 7 (CK7) expression in clear cell renal cell carcinoma (ccRCC) patients by combining multimodal ultrasound diagnostic techniques. METHODS: This retrospective study enrolled 157 surgically confirmed ccRCC patients. All patients underwent pre-operative multimodal ultrasound diagnostic examinations, including B-mode ultrasound (US), color Doppler flow imaging (CDFI) and contrast-enhanced ultrasound (CEUS). The patients were randomly divided into a training group (103 cases) and a testing group (54 cases). Univariate and multivariate logistic regression analyses were performed in the training group to identify independent indicators associated with CK7 positivity. These indicators were included in the predictive model. Receiver operating characteristic (ROC) curves and calibration curves were used to evaluate the model's discriminative ability and accuracy. Decision curve analysis (DCA) and nomogram visualization were used to assess the clinical utility of the predictive model. RESULTS: Univariate logistic regression analysis revealed that US and CDFI observations were not correlated with CK7 expression and could not predict it. Multivariate logistic regression analysis identified age (odds ratio [OR] = 0.953, 95% confidence interval [CI]: 0.909-0.999), wash-in pattern (OR = 0.180, 95% CI: 0.063-0.513) and enhancement homogeneity (OR = 11.610, 95% CI: 1.394-96.675) as independent factors related to CK7 positivity in ccRCC. Incorporating these variables into the predictive model resulted in areas under the receiver operating characteristic curve of 0.812 (95% CI: 0.711-0.913) for the training group and 0.792 (95% CI: 0.667-0.924) for the testing group. The calibration curve and DCA revealed that the model had good accuracy and clinical utility of the model. CONCLUSION: The combination of multimodal ultrasound diagnostic techniques in constructing a predictive model for CK7 expression in ccRCC patients has significant predictive value.

Highly Emissive and Robust Cd-Based MOF with an Unprecedented Topology for Tetracycline Sensing.

Herein, an unprecedented cadmium-based metal-organic framework (JNU-106) fabricated by utilizing pyrazole-functionalized tetraphenylethylene ligands (Py-TPE) and rod-shaped secondary building units is reported, possessing a new (3,3,3,6,6,8)-connected topological network. Thanks to the ingeniously designed intramolecular charge transfer behavior, which originates from the congruent coplanarity between Py and TPE, JNU-106 exhibits intense green luminescence with a quantum yield increased by 1.5 times. The phenomenon of remarkable fluorescence quenching of JNU-106 reveals that it possesses extremely high anti-interference performance, superior sensitivity, and dedicated selectivity toward tetracycline antibiotics (TCAs) in aqueous solutions, which are comparable to those of the state-of-the-art porous sensing compounds. Taking the theoretical calculations and experimental results into account, the luminescence quenching is mainly attributed to the internal filtration effect and the static quenching effect. Considering the portable and rapid performance of JNU-106-based testing strips for sensing TCAs, the fabricated JNU-106 provides an alternative for ecological monitoring and environmental governance.

Longitudinal analysis of quality of life in primary lung cancer patients with chlamydia pneumoniae infection: a time-to-deterioration model.

BACKGROUND: Chlamydia pneumoniae (Cpn) IgG and IgA has been strongly linked to lung cancer, but its impact on patients' quality of life remains unclear. Our objective was to investigate the relationship between pre-treatment Cpn IgG and IgA and time to deterioration (TTD) of the HRQoL in patients with primary lung cancer. METHODS: A prospective hospital-based study was conducted from June 2017 to December 2018, enrolling 82 patients with primary lung cancer admitted to the First Affiliated Hospital of Fujian Medical University for questionnaire surveys. Cpn IgG and IgA was detected by microimmunofluorescence method. HRQoL was assessed at baseline and during follow-up using the EORTC Quality of Life Questionnaire version 3.0 (EORTC QLQ-C30) and EORTC Quality of Life Questionnaire-Lung Cancer (EORTC QLQ-LC13). HRQoL scores were calculated using the QoLR package, and TTD events were determined (minimum clinically significant difference = 5 points). Cox regression analysis was used to evaluate the effect of Cpn IgG and IgA on HRQoL. RESULTS: We investigated the relationship between Cpn IgG and IgA and quality of life in patients with primary lung cancer. The study was found that 75.61% of cases were Cpn IgG + and 45.12% were Cpn IgA + . Cpn IgA + IgG + was 41.46%. For EORTC QLQ-C30, Physical function (PF) and Pain (PA) TTD events on the functional scale and Symptom scale were the most common during follow-up. After adjusting for gender and smoking status, Pre-treatment Cpn IgA + was found to signifcantly delay TTD of Physical functioning(HR = 0.539, 95% CI: 0.291-0.996, P = 0.048). In addition, Cpn IgG + before treatment significantly delayed TTD in Emotional functioning (HR = 0.310, 95% CI: 0.115-0.836, P = 0.021). For EORTC QLQ-LC13, deterioration of dyspnea (LC-DY) was the most common event. However, Cpn IgG and IgA before treatment had no effect on the TTD of EORTC QLQ-LC13 items. CONCLUSIONS: According to EORTC QLQ-C30 and EORTC QLQ-LC13, Cpn IgA delayed TTD in Physical functioning and Cpn IgG delayed TTD in Emotional functioning.

Short-term associations of particulate matter with different aerodynamic diameters with mortality due to mental disorders and dementia in Ningde, China.

Limited evidence is available regarding the impact of ambient inhalable particulate matter (PM) on mental disorder (MD) or dementia-related deaths, particularly PM1, PM1-2.5, and coarse particles (PM2.5-10). Moreover, individual confounders have rarely been considered. In addition, evidence from low-pollution areas is needed but is inadequate. Using death records from the Death Registration System during 2015-2021 in Ningde, a coastal city in southeast China, we combined a conditional quasi-Poisson model with a distributed lag nonlinear model to estimate the nonlinear and lagged associations of PM exposure with MD or dementia-related deaths in Ningde, China, comprehensively controlling for individual time-invariant confounders using a time-stratified case-crossover design. The attributable fraction and number were calculated to quantify the burden of MD or dementia-related deaths that were related to PMs. We found J-shaped relationships between MD or dementia-related deaths and PMs, with different thresholds of 13, 9, 19, 33 and 12 µg/m3 for PM1, PM1-2.5, PM2.5, PM10 and PM2.5-10. An inter-quartile range increase for PM1, PM1-2.5, PM2.5, PM10 and PM2.5-10 above the thresholds led to an increase of 31.8% (95% confidence interval, 14.3-51.9%), 53.7% (22.4-93.1%), 32.6% (15.0-53.0%), 35.1% (17.7-55.0%) and 25.9% (13.0-40.3%) in MD-related deaths at lag 0-3 days, respectively. The associations were significant in the cool season rather than in the warm season and were significantly greater among people aged 75-84 years than in others. The fractions of MD-related deaths attributable to PM1, PM1-2.5, PM2.5, PM10 and PM2.5-10 were 5.55%, 6.49%, 7.68%, 10.66%, and 15.11%, respectively; however, only some of them could be protected by the concentrations recommended by the World Health Organisation or China grade I standard. Smaller associations and similar patterns were observed between PMs and dementia-related death. These findings suggest stricter standards, and provide evidence for the development of relevant policies and measures.

Differentiation Potential of Hypodifferentiated Subsets of Nephrogenic Rests and Its Relationship to Prognosis in Wilms Tumor.

Background Wilms tumor (WT) is highly curable, although anaplastic histology or relapse imparts a worse prognosis. Nephrogenic rests (NR) associated with a high risk of developing WT are abnormally retained embryonic kidney precursor cells. Methods After pseudo-time analysis using single-cell RNA sequencing (scRNA-seq) data, we generated and validated a WT differentiation-related gene (WTDRG) signature to predict overall survival (OS) in children with a poor OS. Results A differentiation trajectory from NR to WT was identified and showed that hypodifferentiated subsets of NR could differentiate into WT. Classification of WT children with anaplastic histology or relapse based on the expression patterns of WTDRGs suggested that patients with relatively high levels of hypodifferentiated NR presented a poorer prognosis. A WTDRG-based risk model and a clinically applicable nomogram was developed. Conclusions These findings may inform oncogenesis of WT and interventions directed toward poor prognosis in WT children of anaplastic histology or relapse.

Key protein identification by integrating protein complex information and multi-biological features.

Identifying key proteins based on protein-protein interaction networks has emerged as a prominent area of research in bioinformatics. However, current methods exhibit certain limitations, such as the omission of subcellular localization information and the disregard for the impact of topological structure noise on the reliability of key protein identification. Moreover, the influence of proteins outside a complex but interacting with proteins inside the complex on complex participation tends to be overlooked. Addressing these shortcomings, this paper presents a novel method for key protein identification that integrates protein complex information with multiple biological features. This approach offers a comprehensive evaluation of protein importance by considering subcellular localization centrality, topological centrality weighted by gene ontology (GO) similarity and complex participation centrality. Experimental results, including traditional statistical metrics, jackknife methodology metric and key protein overlap or difference, demonstrate that the proposed method not only achieves higher accuracy in identifying key proteins compared to nine classical methods but also exhibits robustness across diverse protein-protein interaction networks.

Pyrazine Functionalization in Eu-MOF for Exclusive Ratiometric Luminescence Sensing of PO43.

Single-emission luminescence sensors are less than satisfactory for complex systems due to their susceptibility to environmental disturbances. Lanthanum-based metal-organic frameworks (Ln-MOFs) with highly stable ratiometric dual-emission are regarded as promising luminescence probes owing to their fascinating ligand-to-metal energy transfer behaviors (also known as the antenna effect). Herein, we report the synthesis of a pair of isostructural europium-based MOFs (termed JNU-219 and JNU-220) by utilizing two X-shaped tetracarboxylate linkers, 4,4',4″,4‴-benzene-2,3,5,6-tetrayl-tetrabenzoate (BTEB) and 4,4',4″,4‴-pyrazine-2,3,5,6-tetrayl-tetrabenzoate (BTTB). Both JNU-219 and JNU-220 present the characteristic red luminescence of Eu3+, yet the pyrazine functionalization of the BTTB linker renders JNU-220 with significantly increased luminescence emission, almost 30 times that of JNU-219. As a result, the detection limit of JNU-220 for the ratiometric luminescence sensing of PO43- was determined to be as low as 0.22 µM, which is far superior to those of other reported MOF materials. Additionally, we demonstrate the excellent stability and reusability of JNU-220, further verifying its potential as a robust ratiometric luminescence probe.

The efficacy of robotic-assisted laparoscopic pyeloplasty for pediatric ureteropelvic junction obstruction: a systematic review and meta-analysis.

To evaluate the safety and effectiveness of robotic-assisted laparoscopic pyeloplasty (RALP) for treating pediatric ureteropelvic junction obstruction through an extensive comparison of RALP, open pyeloplasty (OP) and laparoscopic pyeloplasty (LP). We conducted a comprehensive search of the following databases: PubMed, Excerpta Medica Database, Cochrane Library, Web of Science database, China National Knowledge Infrastructure, WanFang Data, and China Biology Medical Disc. Baseline data were compared, the sources of heterogeneity were assessed, and publication biases were detected. This study was registered with PROSPERO (CRD42023415667). 26 studies with 6074 cases performing pyeloplasty were included, and the overall data are comparable. Our analysis showed no significant difference in success rate and postoperative complications between RALP and OP, and RALP is associated with a shorter length of stay (LOS) (MD - 1.00 95%CI - 1.45 to - 0.55, p < 0.0001). In addition, compared to LP, RALP was associated with a shorter anastomosis time (MD - 18.35 95%CI - 29.88 to - 6.82, p = 0.002) and fewer postoperative analgesics (MD - 0.09 95% CI - 0.18 to - 0.01, p = 0.03); however, RALP has a longer operative time (OT) (MD 52.39, 95% CI 39.75-65.03, p < 0.00001) and higher cost. The heterogeneity of OT may be influenced by factors, such as age and region, while the heterogeneity of LOS primarily stems from regional differences. No significant publication bias was detected. Our meta-analysis shows that RALP can be an alternative to OP and LP with a high success rate, minimal postoperative complications, and shorter LOS. In addition, RALP contributes to reduce anastomosis time and postoperative analgesic drugs. However, further well-designed, large-scale, randomized controlled trials with additional parameters are needed to conduct a more comprehensive analysis of heterogeneity.

Structural Design Induced Electronic Optimization in Single-Phase MoCoP Nanocrystal for Boosting Oxygen Reduction, Oxygen Evolution, and Hydrogen Evolution.

Structural and compositional design of multifunctional materials is critical for electrocatalysis, but their rational modulation and effective synthesis remain a challenge. Herein, a controllable one-pot synthesis for construction of trifunctional sites and preparation of porous structures is adopted for synthesizing dispersed MoCoP sites on N, P codoped carbonized substance. This tunable synthetic strategy also endorses the exploration of the electrochemical activities of Mo (Co)-based unitary, Mo/Co-based dual and MoCo-based binary metallic sites. Eventually benefiting from the structural regulation, MoCoP-NPC shows excellent oxygen reduction abilities with a half-wave potential of 0.880 V, and outstanding oxygen evolution and hydrogen evolution performance with an overpotential of 316 mV and 91 mV, respectively. MoCoP-NPC-based Zn-air battery achieves excellent cycle stability for 300 h and a high open-circuit voltage of 1.50 V. When assembled in a water-splitting device, MoCoP-NPC reaches 10 mA cm-2 at 1.65 V. Theoretical calculations demonstrate that the Co atom in the single-phase MoCoP has a low energy barrier for oxygen evolution reaction (OER) owing to the migration of Co 3d orbital toward the Fermi level. This work shows a simplified method for controllable preparation of prominent trifunctional catalysts.

Near complete response to ceritinib in a pediatric patient with metastatic ALK-rearranged lung adenocarcinoma.

Anaplastic lymphoma kinase (ALK) inhibitors have significant efficacies in ALK-rearranged non-small cell lung cancers (NSCLC). In regard to pediatric NSCLC patients, however, there is a paradox in that on the one hand, they may have a higher probability of ALK-rearrangement positive, but on the other hand, there is no sufficient data for efficacies of ALK inhibitors in pediatric NSCLC patients. Here, we present an 11-year-old boy diagnosed with metastatic ALK-rearranged lung adenocarcinoma. He was treated with ceritinib 450 mg with food once daily and has obtained near complete response in 18th month, with a largely regressed intrathoracic lesion and only localized residual distant metastatic disease. Meanwhile, he showed continued good tolerance after a short period of side effects at the beginning of the dose. This is the first report of the use of ceritinib in pediatric patient with NSCLC.

Association between physical activity and health-related quality of life: time to deterioration model analysis in lung adenocarcinoma.

BACKGROUND AND PURPOSE : Health-related quality of life (HRQoL) is a key aspect of care for cancer survivors that can be improved by physical activity. Our aim was to explore the relationship between physical activity and time to deterioration (TTD) of the HRQoL in patients with lung adenocarcinoma (LUAD). METHODS: We conducted a hospital-based prospective study. The International Physical Activity Questionnaire long-form (IPAQ-L) was used to investigate the pre-treatment physical activity levels, and the EORTC Quality of Life Questionnaire version 3.0 (EORTC QLQ-C30) and EORTC Quality of Life Questionnaire-Lung Cancer (EORTC QLQ-LC13) were used to assess HRQoL at baseline and during follow-up. The QoLR package was used to calculate the HRQoL scores and determine TTD events (minimal clinically important difference=5 points). The effect of physical activity on the HRQoL was assessed using Cox regression analysis. RESULTS: For EORTC QLQ-C30, TTD events of physical functioning (PF) and dyspnea (DY) in functional scales and symptom scales were the most common during follow-up. Pre-treatment physical activity was found to significantly delay TTD of insomnia (HR=0.635, 95%CI: 0.437-0.922, P=0.017) and diarrhea (HR=0.475, 95%CI: 0.291-0.774, P=0.003). For EORTC QLQ-LC13 scales, deterioration of dyspnea (LC-DY) was the most common event. Physical activity was found to delay the TTD of dyspnea (HR=0.654, 95%CI: 0.474-0.903, P=0.010), sore mouth (HR=0.457, 95%CI: 0.244-0.856, P=0.015), and dysphagia (HR=0.315, 95%CI: 0.172-0.580, P<0.001). CONCLUSIONS: Pre-treatment physical activity of LUAD patients may delay the TTD of multiple HRQoL indicators in EORTC QLQ-C30 and EORTC QLQ-LC13. IMPLICATION FOR CANCER SURVIVORS: Health-related quality of life (HRQoL) is a key aspect of care for cancer survivors (someone who is living with or beyond cancer), that can be improved by physical activity. Our aim was to explore the relationship between physical activity and time to deterioration (TTD) of the HRQoL in patients with lung adenocarcinoma (LUAD).

Beliefs and perceptions of electronic cigarettes among medical staff in respiratory departments of Fujian Province, China, in 2021.

INTRODUCTION: Due to the popularity of e-cigarettes, more and more patients ask about e-cigarettes, and it is particularly important to understand doctors' beliefs and perceptions on e-cigarettes. The aim was to evaluate the belief and perception of electronic cigarettes among medical staff in the respiratory department of medical institutions located in Fujian Province. METHODS: The electronic questionnaires were conveyed to the medical staff of the respiratory department in Fujian Province during March to April 2021. Descriptive statistics were calculated for all questions, and the relationship between relevant factors and the perception of e-cigarette-related statements was analyzed by logistic regression analysis. RESULTS: Among 1028 medical staff in the respiratory departments of Fujian Province, 90.5% of medical staff agreed that electronic cigarettes are harmful to the human body; 61.4% of medical staff agreed that e-cigarettes cannot be regarded as a type of smoking cessation treatment; 71.7% of medical staff agreed that e-cigarettes could be a 'gateway' to other tobacco use; and 69.2% of medical staff agreed that electronic cigarettes are in 'Three No' states. The multivariate logistic regression analysis showed that the respondents' perception of 'e-cigarettes cannot be regarded as a type of smoking cessation treatment' were related to gender, professional title and whether they participated in the cessation clinic. CONCLUSIONS: The medical staff of the respiratory department in Fujian Province put more emphasis on the adverse effects of e-cigarettes on health, but lack the cognition of the effect of e-cigarette smoking cessation. In order to better carry out smoking cessation work, it is necessary to strengthen the training of respiratory medical staff at all levels of medical institutions on e-cigarette knowledge.

Pharmacokinetics and bioequivalence of two imidocarb formulations in cattle after subcutaneous injection.

Imidocarb (IMD) is commonly used for treatment of eperythrozoon, babesia, piroplasma and trypanosoma in animals, but there are few studies on its pharmacokinetics in cattle. The purpose of this study was to obtain pharmacokinetic parameters and assess the bioequivalence of subcutaneous injections of two IMD formulations in cattle. Forty-eight healthy cattle, 24 males and 24 females, were randomLy divided into two groups (test group and reference group) with 12 males and 12 females per group. The generic IMD was injected subcutaneously with a single dose of 3.0 mg/kg in the test group. Reference group animals were given one injection of the marketed IMD at the same dosage. The limit of detection (LOD) and limit of quantification (LOQ) for IMD in cattle plasma were 0.05 ng/mL and 0.1 ng/mL, respectively. The recoveries ranged from 88.50% to 92.42%, and the equation of this calibration curve was Y = 13672.1X+187.43. The pharmacokinetics parameters of the test group showed that the maximum concentration of 2257.5±273.62 ng/mL was obtained at 2.14±0.67 h, AUC0-t 14553.95±1946.85 ng·h/mL, AUC∞ 15077.88±1952.19 ng·h/mL, T1/2 31.77±25.75 h, CL/F 0.14±0.02 mL/h/g, and Vz/F 6.53±5.34 mL/g. There was no significant difference in AUC0-t, AUC∞ and Cmax between the test group and the reference group (P>0.05). The 90% confidence interval of AUC0-t, AUC0-∞ and Cmax in the test group was included in 80%-125% AUC0-t, AUC0-∞ and 70%-143% Cmax in the reference group, respectively. Based on these results, the two preparations were found to be bioequivalent.

Construction of an immune-related lncRNA signature pair for predicting oncologic outcomes and the sensitivity of immunosuppressor in treatment of lung adenocarcinoma.

BACKGROUND: Although immunotherapy has shown clinical activity in lung adenocarcinoma (LUAD), LUAD prognosis has been a perplexing problem. We aimed to construct an immune-related lncRNA pairs (IRLPs) score for LUAD and identify what immunosuppressor are appropriate for which group of people with LUAD. METHODS: Based on The Cancer Genome Atlas (TCGA)-LUAD cohort, IRLPs were identified to construct an IRLPs scoring system by Cox regression and validated in the Gene Expression Omnibus (GEO) dataset using log-rank test and the receiver operating characteristic curve (ROC). Next, we used spearman's correlation analysis, t-test, signaling pathways analysis and gene mutation analysis to explore immune and molecular characteristics in different IRLP subgroups. The "pRRophetic" package was used to predict the sensitivity of immunosuppressant. RESULTS: The IRLPs score was constructed based on eight IRLPs calculated as 2.12 × (MIR31HG|RRN3P2) + 0.43 × (NKX2-1-AS1|AC083949.1) + 1.79 × (TMPO-AS1|LPP-AS2) + 1.60 × (TMPO-AS1|MGC32805) + 1.79 × (TMPO-AS1|PINK1-AS) + 0.65 × (SH3BP5-AS1|LINC01137) + 0.51 × (LINC01004|SH3PXD2A-AS1) + 0.62 × (LINC00339|AGAP2-AS1). Patients with a lower IRLPs risk score had a better overall survival (OS) (Log-rank test P TCGA train dataset < 0.001, P TCGA test dataset = 0.017, P GEO dataset = 0.027) and similar results were observed in the AUCs of TCGA dataset and GEO dataset (AUC TCGA train dataset = 0.777, AUC TCGA test dataset = 0.685, AUC TCGA total dataset = 0.733, AUC GEO dataset = 0.680). Immune score (Cor = -0.18893, P < 0.001), stoma score (Cor = -0.24804, P < 0.001), and microenvironment score (Cor = -0.22338, P < 0.001) were significantly decreased in the patients with the higher IRLP risk score. The gene set enrichment analysis found that high-risk group enriched in molecular changes in DNA and chromosomes signaling pathways, and in this group the tumor mutation burden (TMB) was higher than in the low-risk group (P = 0.0015). Immunosuppressor methotrexate sensitivity was higher in the high-risk group (P = 0.0052), whereas parthenolide (P < 0.001) and rapamycin (P = 0.013) sensitivity were lower in the high-risk group. CONCLUSIONS: Our study established an IRLPs scoring system as a biomarker to help in the prognosis, the identification of molecular and immune characteristics, and the patient-tailored selection of the most suitable immunosuppressor for LUAD therapy.

Immune-Related Molecular Profiling of Thymoma With Myasthenia Gravis.

Background: Approximately 50% of thymoma patients also show myasthenia gravis (MG), which is an autoimmune disease; however, the pathogenesis of MG-associated thymoma remains elusive. Our aim was to investigate immune-related lncRNA profiles of a set of candidate genes for better understanding of the molecular mechanism underlying the pathogenesis of thymoma with or without MG. Methods: Molecular profiles of thymoma with or without MG were downloaded from The Cancer Genome Atlas, and Pearson's correlation analysis was performed to identify immune-related lncRNAs. T test was used to examine the differential expression and differential methylation between thymoma patients with or without MG. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to predict the function of target genes of immune-related lncRNAs. Results: Analyses of the 87 thymoma samples with complete MG information revealed that 205 mRNAs and 56 lncRNAs showed up-regulated expression in thymoma with MG patients, while 458 mRNAs and 84 lncRNAs showed down-regulated expression. The methylation level of three immune-related lncRNAs (AP000787.1, AC004943.1, WT1-AS, FOXG1-AS1) was significantly decreased in thymoma tissues, and the methylation level of these immune-related lncRNAs (WT1-AS: Cor = 0.368, p < 0.001; FOXG1-AS1: Cor = 0.288, p < 0.01; AC004943.1: Cor = -0.236, p < 0.05) correlated with their expression. GO and KEGG pathway analysis revealed that targets of the immune-related lncRNA FOXG1-AS1 were enriched in small GTPase binding and herpes simplex virus 1 infection. Transcription coregulator activity and cell cycle were the most enriched pathways for targets of lncRNA AC004943.1. LncRNA WT1-AS targets were most enriched in actin binding and axon guidance. Conclusion: Our results revealed the immune-related molecular profiling of thymoma with MG and without MG and identified key pathways involved in the underlying molecular mechanism of thymoma-related MG. These findings provide insights for further research of potential markers for thymoma-related MG.

Overexpression of close homolog of L1 enhances the chemosensitivity of lung cancer cells via inhibition of the Akt pathway.

Drug resistance leads to tumor relapse and further progression during chemotherapy in lung cancer. Close homolog of L1 (CHL1) has been identified as a tumor suppressor in most malignancies. However, to the best of our knowledge, whether CHL1 mediates chemoresistance remains unknown. The present study observed that CHL1 was significantly downregulated in cisplatin (DDP)-resistant cells (A549/DDP) and paclitaxel (PTX)-resistant cells (A549/PTX) compared with A549 cells. When treated with or without DDP and PTX, silencing of CHL1 in A549 cells promoted the cell survival rate and clone formation, and decreased apoptosis. Whereas overexpression of CHL1 in A549/DDP and A549/PTX cells impeded the cell survival and clone formation and promoted apoptosis. Additionally, CHL1 overexpression enhanced the chemosensitivity of A549/DDP cells to DDP in vivo. Notably, the chemoresistance induced by CHL1 depletion was reversed by the Akt inhibitor SC66 in A549 cells. The results of the present study demonstrated that CHL1 enhanced sensitivity of lung cancer cells by suppressing the Akt pathway, which suggested that CHL1 may be a potential target for overcoming chemoresistance in lung cancer.