Formation and toxicity contribution of chlorinated and dechlorinated halobenzoquinones from dichlorophenols after ozonation.

Halobenzoquinones (HBQs) are a class of disinfection byproducts with high cytotoxicity and potential carcinogenicity, which have been widely detected in chlorination of drinking water and swimming pool water. However, to date, the formation of HBQs upon ozonation and the HBQ precursors have been overlooked. This study investigated the formation of chlorinated and dechlorinated HBQs from six dichlorophenol (DCP) isomers. The monomeric and dimeric HBQs were identified in all the ozonation effluents, exhibiting 1-100 times higher toxicity levels than their precursors. The sum of detected HBQs intensity had a satisfactory linear relation with the maximum toxic unit (R2 = 0.9657), indicating the primary toxicity contribution to the increased overall toxicity of effluents. Based on density functional theory calculations, when ozone attacks the para carbon to the hydroxyl group of 2,3-DCP, the probability of producing chlorinated HBQs is 80.41 %, indicating that the para carbon attack mainly resulted in the formation of monomeric HBQs. 2,3-dichlorophenoxy radicals were successfully detected in ozonated 2,3-DCP effluent through electron paramagnetic resonance and further validated using theoretical calculation, revealing the formation pathway of dimeric HBQs. The results indicate that chlorinated phenols, regardless of the positions of chlorine substitution, can potentially serve as precursors for both chlorinated and dechlorinated HBQs formation during ozonation.

EGFR co-mutation is associated with the risk of recurrence in invasive lung adenocarcinoma with the micropapillary component.

BACKGROUND: Invasive lung adenocarcinoma (LUAD) patients with the micropapillary (MPP) component tend to have extremely poor prognosis. To optimize clinical outcomes, a better understanding of specific concurrent gene alterations and their impact on the prognosis of patients with the MPP component is necessary. METHOD: A total of 621 Chinese patients with surgically resected invasive LUAD who underwent genetic testing for lung cancer were enrolled in this retrospective study. The genomic profiling of major lung cancer-related genes based on next-generation sequencing (NGS) was carried out on formalin-fixed paraffin-embedded tumor samples. RESULT: Among 621 patients with invasive LUAD, 154 (24.8%, 154/621) had the MPP component. We found that PIK3CA (4.5% vs 1.3%), KRAS (9.1% vs 4.7%), and ROS1 (2.6% vs 0.4%) were more frequent in patients with the MPP component than those without the MPP component (P < 0.05). The co-mutation occurred in 66 patients (10.6%, 66/621), of which 19 patients with the MPP component. Most of them were EGFR co-mutations (89.5%, 17/19), including EGFR and PIK3CA, EGFR and ERBB2, and other types. Patients with the MPP component who harbored EGFR co-mutations showed significantly worse recurrence-free survival (RFS) than single EGFR mutation (median RFS 20.1 vs 30.5 months; hazard ratio [HR]: 8.008; 95% confidence interval [CI]: 1.322-48.508). CONCLUSIONS: Patients with the MPP component harbored the co-mutation of driver genes had a higher risk of recurrence after surgery, especially in patients with EGFR co-mutation. EGFR co-mutation was a significant prognostic factor for RFS in patients with the MPP component.

PFKP confers chemoresistance by upregulating ABCC2 transporter in non-small cell lung cancer.

Background: Chemoresistance is a significant factor contributing to tumor recurrence and treatment failure in non-small cell lung cancer (NSCLC). The phosphofructokinase, platelet (PFKP) is highly expressed in NSCLC and is associated with a poor prognosis. Exploring the molecular mechanism and identifying effective strategies to overcome chemoresistance will have important clinical significance in improving the diagnosis and treatment of NSCLC. Methods: The correlation between PFKP and cisplatin resistance in NSCLC patients was assessed by organoids and immunohistochemistry. The impact of PFKP on the prognosis of NSCLC patients was analyzed using The Cancer Genome Atlas (TCGA) database. In NSCLC cell lines, the expression of PFKP was modulated using lentivirus, and cisplatin sensitivity was assessed by flow cytometry. Subsequently, the therapeutic effect of cisplatin was tested in BALB/c nude mice implanted subcutaneously with tumor cells. We performed luciferase assay and immunohistochemistry (IHC) to investigate the correlation between PFKP and ABCC2 (ATP-binding cassette sub-family C member 2). Results: Overexpression of PFKP was correlated with poorer survival rates in NSCLC patients who received platinum-based chemotherapy. Using NSCLC organoid, we found that the expression of PFKP was elevated in cisplatin (CDDP)-resistant patients with NSCLC. Overexpression of PFKP decreased the sensitivity of NSCLC cells to CDDP, while genetic inhibition of PFKP enhanced CDDP sensitivity both in vitro and in vivo. Furthermore, we found that PFKP upregulated ABCC2 by increasing the levels of phosphorylation of IκBα and nuclear p65 NF-κB subunit protein. Conclusions: PFKP can regulate the expression of ABCC2 through the activation of NF-κB, which in turn promotes chemoresistance in NSCLC. PFKP has the potential to be a personalized therapeutic target for NSCLC patients with chemoresistance.

Deep learning-based solid component measuring enabled interpretable prediction of tumor invasiveness for lung adenocarcinoma.

BACKGROUND: The nature of the solid component of subsolid nodules (SSNs) can indicate tumor pathological invasiveness. However, preoperative solid component assessment still lacks a reference standard. METHODS: In this retrospective study, an AI algorithm was proposed for measuring the solid components ratio in SSNs, which was used to assess the diameter ratio (1D), area ratio (2D), and volume ratio (3D). The radiologist measured each SSN's consolidation to tumor ratio (CTR) twice, four weeks apart. The area under the receiver-operating characteristic (ROC) curve (AUC) was calculated for each method used to discriminate an Invasive Adenocarcinoma (IA) from a non-IA. The AUC and the time cost of each measurement were compared. Furthermore, we examined the consistency of measurements made by the radiologist on two separate occasions. RESULTS: A total of 379 patients (the primary dataset n = 278, the validation dataset n = 101) were included. In the primary dataset, compared to the manual approach (AUC: 0.697), the AI algorithm (AUC: 0.811) had better predictive performance (P =.0027) in measuring solid components ratio in 3D. Algorithm measurement in 3D had an AUC no inferior to 1D (AUC: 0.806) and 2D (AUC: 0.796). In the validation dataset, the AI 3D method also achieved superior diagnostic performance compared to the radiologist (AUC: 0.803 vs 0.682, P =.046). The two measurements of the CTR in the primary dataset, taken 4 weeks apart, have 7.9 % cases in poor consistency. The measurement time cost by the radiologist is about 60 times that of the AI algorithm (P <.001). CONCLUSION: The 3D measurement of solid components using AI, is an effective and objective approach to predict the pathological invasiveness of SSNs. It can be a preoperative interpretable indicator of pathological invasiveness in patients with lung adenocarcinoma.

TNF-α and IL-8 levels are positively correlated with hypobaric hypoxic pulmonary hypertension and pulmonary vascular remodeling in rats.

The expression status of proinflammatory cytokines in high-altitude pulmonary arterial hypertension (PAH) has been well studied. However, the changes in interleukin (IL)-8 and tumor necrosis factor α (TNF-α) during the reversible changes in pulmonary vascular remodeling (PVR) in PAH after detaching from a hypobaric hypoxic environment have not been elucidated. This investigation elucidated a high-altitude PAH rat model. Then, PAH rats in the high-altitude group were maintained in the high-altitude area, and rats in the low-altitude group returned to the low-altitude area. After 0, 10, 20, and 30 days of PAH modeling, right ventricular systolic pressure (RVSP) and the mean pulmonary arterial pressure (mPAP) were assessed. Right ventricular (RV) hypertrophy was reflected by the ratio of RV/[left ventricle + interventricular septum (S)]. Pathological changes in PVR were accessed by hematoxylin-eosin staining, and medial wall thickness (WT%) and medial wall area (WA%) were measured. TNF-α and IL-8 levels in pulmonary artery tissues and blood were measured with Western blot assay and enzyme-linked immunosorbent assay, respectively. Our results showed that PAH rats exhibited a substantial increase in RVSP and mPAP, RV hypertrophy, PVR, and enhanced generation of TNF-α and IL-8. Then, we found that these pathological changes were gradually aggravated and TNF-α and IL-8 levels were increased in rats in the high-altitude group after 10, 20, and 30 days of PAH modeling. In contrast, the mPAP was decreased and PVR was alleviated in rats in the low-altitude group, accompanying with reduced TNF-α and IL-8 production. In conclusion, our study demonstrated that the generation of TNF-α and IL-8 was also reversible during the reversible changes in PVR after detaching from a hypobaric hypoxic environment. Thus, proinflammatory cytokine TNF-α and IL-8 levels are positively correlated with PVR severity.

Invasiveness assessment by artificial intelligence against intraoperative frozen section for pulmonary nodules ≤ 3 cm.

PURPOSE: To investigate the performance of an artificial intelligence (AI) algorithm for assessing the malignancy and invasiveness of pulmonary nodules in a multicenter cohort. METHODS: A previously developed deep learning system based on a 3D convolutional neural network was used to predict tumor malignancy and invasiveness. Dataset of pulmonary nodules no more than 3 cm was integrated with CT images and pathologic information. Receiver operating characteristic curve analysis was used to evaluate the performance of the system. RESULTS: A total of 466 resected pulmonary nodules were included in this study. The areas under the curves (AUCs) of the deep learning system in the prediction of malignancy as compared with pathological reports were 0.80, 0.80, and 0.75 for all, subcentimeter, and solid nodules, respectively. Additionally, the AUC in the AI-assisted prediction of invasive adenocarcinoma (IA) among subsolid lesions (n = 184) was 0.88. Most malignancies that were misdiagnosed by the AI system as benign diseases with a diameter measuring greater than 1 cm (26/250, 10.4%) presented as solid nodules (19/26, 73.1%) on CT. In an exploratory analysis involving nodules underwent intraoperative pathologic examination, the concordance rate in identifying IA between the AI model and frozen section examination was 0.69, with a sensitivity of 0.50 and specificity of 0.97. CONCLUSION: The deep learning system can discriminate malignant diseases for pulmonary nodules measuring no more than 3 cm. The AI model has a high positive predictive value for invasive adenocarcinoma with respect to intraoperative frozen section examination, which might help determine the individualized surgical strategy.

Minigene Assay as an Effective Molecular Diagnostic Strategy in Determining the Pathogenicity of Noncanonical Splice-Site Variants in FLCN.

Primary spontaneous pneumothorax (PSP) or pulmonary cyst is one of the manifestations of Birt-Hogg-Dubé syndrome, which is caused by pathogenic variants in FLCN gene. Genetic testing in patients with PSP identifies a certain number of missense or intronic variants. These variants are usually considered as variants of uncertain significance, whose functional interpretations pose a challenge in clinical genetics. To improve recognition of pathogenic splice-altering variants in FLCN gene, computational tools are used to prioritize potential splice-altering variants and then a hybrid minigene assay is performed to verify the RNA splicing pattern. Herein, variants in FLCN exon 11 and its flanking sequence are focused. Eight variants detected in 11 patients with PSP are evaluated, and six variants are prioritized by in silico tools as potential splice-altering variants of uncertain significance. Four variants (c.1177-5_1177-3delCTC, c.1292_1300+4del, c.1300+4C>T, and c.1300+5G>A) are demonstrated by minigene assay to alter RNA splicing of FLCN, and the last three of them are novel. RT-PCR of patient-derived RNA gives consistent results. Genotype-phenotype correlation analysis in patients with PSP with these variants demonstrates good concordance. Our results underline the importance of RNA analysis, which could provide molecular evidence for pathogenicity of a variant, and provide essential information for the clinical interpretation of variants. Combining the clinical information, a definitive diagnosis could be made.

Extracorporeal membrane oxygenation (ECMO)-assisted surgery for traumatic bronchial rupture: a report of three cases.

Background: Traumatic tracheal rupture is a severe closed chest injury that often causes major respiratory and circulatory disturbances requiring emergency surgery. We have found that veno-venous extracorporeal membrane oxygenation (VV-ECMO) employs lung-protective ventilation strategies to facilitate lung rest, aiming to minimize the risk of ventilator-induced lung injury, while ensuring adequate oxygenation. Case Description: We presented 3 critically ill patients who presented with traumatic bronchial rupture between 2019 and 2021, and underwent emergency thoracic surgery with the help of VV-ECMO. The ECMO support time, the operative time, the duration of postoperative hospital stay, and the postoperative mechanical ventilation time were collected in this study. All patients were successfully treated and discharged home. The duration of surgery ranged from 135 to 180 min, the duration of ECMO use ranged from 98 to 123 h, the duration of postoperative ventilator use ranged from 5 to 8 days, and the duration of postoperative hospital stay ranged from 14 to 30 days. All 3 patients had good postoperative pulmonary re-expansion, with no residual tracheal or bronchial stenosis, and good physical activity following the surgery. Conclusions: We reported successful use of VV-ECMO in critically ill patients with traumatic bronchial rupture presenting in acute respiratory and circulatory failure. Performing emergency surgery with ECMO-assisted support can provide more time to stabilize the patient and ensure the safety of the procedure. However, considering the small sample size of this study, larger cohorts with long-term follow-up data are needed to further evaluate its application.

Perioperative Management of Patient with Esophageal Carcinoma and Crigler-Najjar Syndrome Type 2: A Case Report.

Background: Crigler-Najjar syndrome type 2 (CNS-II) is a rare genetic disease that is associated with a lack of uridine diphosphate-glucuronosyltransferase. Esophageal carcinoma is the sixth most common cause of cancer-related death worldwide, for which surgery is the most effective treatment. Reports on patients with both conditions requiring surgery are limited and The impact of hyperbilirubinemia caused by CNS-II on the perioperative period is unknown. Previous studies have found that patients with Crigler-Najjar syndrome have an increased risk of gallstones and related complications, which also poses corresponding challenges to the treatment. Herein, we present a patient with CNS-II who underwent successful thoracoscopic surgery for esophageal carcinoma. Case summary: A 65-year-old male presented to our hospital with a choking sensation after eating. A physical examination showed yellowing of the sclera and skin. The patient manifested persistent jaundice since birth and had visited many hospitals, but the cause remained undiagnosed. We performed genetic testing, which confirmed CNS-II. Gastroscopy indicated esophageal carcinoma. A multidisciplinary team discussion was carried out to determine the appropriate treatment and perioperative management for this patient. The results show that surgical resection was the most appropriate approach. Finally, the patient underwent thoracoscopic surgery for esophageal carcinoma without complications. Conclusion: Esophageal carcinoma in patients with Crigler-Najjar syndrome is a rare case, and perioperative management is key in the treatment process. It is necessary to pay close attention to the changes of the disease to prevent complications.

Engineering of 177Lu-labeled gold encapsulated into dendrimeric nanomaterials for the treatment of lung cancer.

As a novel type of theranostic radioactive agents, 177Lu-labeled nanomaterials conjugated to macromolecules have been described. The study aimed to fabricate PAMAM-G4-(177Lu-dendrimer)-bombesin-folate in the dendrimeric cavity, assess the radiopharmaceutical ability for specifically targeted radiotherapy and simultaneously detects gastrin-releasing peptide receptors (GRPR) and folate receptors (FRs) overexpressed in lung carcinoma cells, respectively. In an aqueous-basic media, p-SCN-benzyl-DOTA was conjugated to the dendrimer. This dendrimer was formed by activating the carboxylic acid groups of DOTA-folic acid and bombesin with HATU and conjugating them to develop the dendrimer. As part of this process, the conjugate was combined with 1% HAuCl4, added NaBH4 and filtered by ultrafiltration. Infrared, UV-Vis, TEM analysis, dynamic light scattering (DLS), and fluorescence spectroscopy were employed to observe the composition of the fabricated sample. Radio-labeled 177LuCl3 was used to label the conjugate, which was then evaluated using the radio-HPLC method. Findings demonstrated dendrimeric functionalization with remarkable radiochemical composition purity up to >96%. Because of fluorescence studies, it was determined that the occurrence of AuNMs in the dendrimeric cavities gives beneficial photo-physical characteristics to the radiopharmaceutical for bio-imaging. HEL-299 lung cancer cells exhibited a selective absorption of the drug (%). It might be helpful as nuclear and optical imaging agents for lung cancers that overexpress FRs and GRPR and as a specific target for radiation therapy if combined with folate-bombesin.

Pathological complete response after neoadjuvant treatment determines survival in esophageal squamous cell carcinoma patients (NEOCRTEC5010).

BACKGROUND: Few studies have exclusively investigated the value of pathological complete response (pCR), in esophageal squamous cell carcinoma (ESCC) patients, although it is a clinically significant parameter to evaluate the impact of neoadjuvant chemoradiotherapy (nCRT) on treatment outcome after surgery. The aim of our study was to explore the relationship between pCR after nCRT and survival among patients with local ESCC. METHODS: All patients receiving nCRT followed by surgery in NEOCRTEC5010-trial (NCT01216527) were included. Non-pCR patients were classified into three subgroups: ypTanyN0M0, ypT0NanyM0 and ypTanyNanyM0. The Kaplan-Meier method with log-rank test was employed to evaluate disease-free survival (DFS) and overall survival (OS). Multivariate regression analysis was performed using a Cox proportional hazards model to identify clinicopathological parameters associated with pCR. RESULTS: Among the 185 patients included, 80 (43.2%) achieved pCR after nCRT. The mean survival time of the pCR group was significantly longer than that of the non-pCR group (92.6 vs. 69.2 months; HR, 2.70; 95% CI: 1.48-4.92; P=0.001). The 5-year OS and DFS of the pCR group were 79.3% and 77% respectively, compared to 54.8% and 51.2%, respectively, in the non-pCR group. The results showed that the OS and DFS of the ypTanyN0M0 group were better than those of the ypT0NanyM0 group and the ypTanyNanyM0 group. We also found that the number of dissected lymph nodes and pCR were independent risk factors for DFS and OS rates. CONCLUSIONS: pCR after nCRT is an important prognostic indicator of OS and DFS in patients with ESCC. In addition, lymph-node status could represent an important parameter in the prognostic evaluation of esophageal cancer patients.

Analysis of Gut Microbiota Composition in Lung Adenocarcinoma Patients with TCM Qi-Yin Deficiency.

In Lung adenocarcinoma (ADC), Qi-Yin deficiency syndrome (QY) is the most common Traditional Chinese medicine (TCM) syndrome. This study aimed to investigate the diversity and composition of gut microbiota in ADC patients with QY syndrome. 90 stool samples, including 30 healthy individuals (H), 30 ADC patients with QY syndrome, and 30 ADC patients with another syndrome (O) were collected. Then, 16s-RNA sequencing was used to analyze stool samples to clarify the structure of gut microbiota, and linear discriminant analysis (LDA) effect size (LEfSe) was applied to identify biomarkers for ADC with QY syndrome. Logistic regression analysis was performed to establish a diagnostic model for the diagnosis of QY syndrome in ADC patients, which was assessed with the AUC. Finally, 20 fecal samples (QY: 10; O: 10) were analyzed with Metagenomics to validate the diagnostic model. The [Formula: see text] diversity and [Formula: see text] diversity demonstrated that the structure of gut microbiota in the QY group was different from that of the H group and O group. In the QY group, the top 3 taxonomies at phylum level were Firmicutes, Bacteroidetes, and Proteobacteria, and at genus level were Faecalibacterium, Prevotella_9, and Bifidobacterium. LEfSe identified Prevotella_9 and Streptococcus might be the biomarkers for QY syndrome. A diagnostic model was constructed using those 2 genera with the AUC = 0.801, similar to the AUC based on Metagenomics (0.842). The structure of gut microbiota in ADC patients with QY syndrome was investigated, and a diagnostic model was developed for the diagnosis of QY syndrome in ADC patients, which provides a novel idea for the understanding and diagnosis of TCM syndrome.

Identification of P2RY13 as an immune-related prognostic biomarker in lung adenocarcinoma: A public database-based retrospective study.

BACKGROUND: Lung adenocarcinoma (LUAD) is the leading histological subtype of non-small cell lung cancer (NSCLC). METHODS: In the present study, the gene matrixes of LUAD were downloaded from The Cancer Genome Atlas to infer immune and stromal scores with the 'Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data' (ESTIMATE) algorithm and identified immune-related differentially expressed genes (DEGs) between the high- and low-stromal/immune score groups. Next, all DEGs were subjected to univariate Cox regression and survival analyses to screen out prognostic biomarkers in the tumor microenvironment (TME), and were validated in the Gene Expression Omnibus database. Single-sample gene set enrichment analysis (ssGSEA) was performed to assess the level of tumor-infiltrating immune cells (TIICs) and immune functions, and GSEA was used to identified pathways altered by prognostic biomarkers. RESULTS: Survival analysis showed that LUAD in the high-immune and stromal score group had a better clinical prognosis. A total of 303 immune-related DEGs were detected. Univariate Cox regression and survival analyses revealed that P2Y purinoceptor 13 (P2RY13) was a favorable factor for the prognosis of LUAD. ssGSEA and Spearman correlation analysis demonstrated that P2RY13 was highly correlated with various TIICs and immune functions. Several immune-associated pathways were enriched between the high- and low-expression P2RY13 groups. CONCLUSION: P2RY13 may be a potential prognostic indicator and is highly associated with the TME in LUAD. However, further experimental studies are required to validate the present findings.

Identification of a ferroptosis-related gene signature (FRGS) for predicting clinical outcome in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common pathological subtype of lung cancer. Ferroptosis, an oxidative, iron-dependent form of necrotic cell death, is highly associated with tumorigenesis and cancer progression. However, the prognostic value of ferroptosis progress in LUAD was still rarely be investigated. METHODS: Herein, we collected three mRNA expression profiles and 85 ferroptosis-related genes from public databases. The "limma" package was used to identify ferroptosis-related differentially expressed genes (DEGs). Univariate Cox regression analysis and LASSO regression analysis were applied to screen and develop a ferroptosis-related gene signature (FRGS) and a formula to calculate the risk score. Multivariate Cox regression analysis was implemented to determine independent prognostic predictors of overall survival (OS). The area under the receiver operating characteristic curve (AUC) and calibration plot were used to evaluate the predictive accuracy of the FRGS and nomogram. RESULTS: We developed a FRGS with five genes (CYBB, CISD1, FADD, SAT2, VDAC2). The AUC of the FRGS in TCGA cohort was 0.777 at 1-year, 0.721 at 3-year and 0.725 at 5-year, significantly superior to the AUC of TNM stage (1-year: 0.701, 3-year: 0.691, 5-year: 0.686). A similar phenomenon was observed in GEO cohort 1 and 2. Multivariate Cox regression analysis indicted TNM stage and risk score were independent prognostic predictors. Finally, we built a nomogram with TNM stage and FRGS, the AUCs of which markedly higher than that of FRGS or TNM stage alone. CONCLUSION: We constructed a prognostic FRGS with five ferroptosis-related genes and a nomogram for predicting the 1-, 3- and 5-year survival rate of LUAD patients, which may provide a new understanding of the prognostic value of ferroptosis progress in LUAD and will benefit prognosis assessment of LUAD patients.

A Novel FLCN Intragenic Deletion Identified by NGS in a BHDS Family and Literature Review.

Birt-Hogg-Dubé syndrome (BHDS, MIM #135150), caused by germline mutations of FLCN gene, is a rare autosomal dominant inherited disorder characterized by skin fibrofolliculomas, renal cancer, pulmonary cysts and spontaneous pneumothorax. The syndrome is considered to be under-diagnosed due to variable and atypical manifestations. Herein we present a BHDS family. Targeted next generation sequencing (NGS) and multiplex ligation-dependent probe amplification (MLPA) revealed a novel FLCN intragenic deletion spanning exons 10-14 in four members including the proband with pulmonary cysts and spontaneous pneumothorax, one member with suspicious skin lesions and a few pulmonary cysts, as well as two asymptomatic family members. In addition, a linkage analysis further demonstrated one member with pulmonary bullae to be a BHDS-ruled-out case, whose bullae presented more likely as an aspect of paraseptal emphysema. Furthermore, the targeted NGS and MLPA data including our previous and present findings were reviewed and analyzed to compare the advantages and disadvantages of the two methods, and a brief review of the relevant literature is included. Considering the capability of the targeted NGS method to detect large intragenic deletions as well as determining deletion junctions, and the occasional false positives of MLPA, we highly recommend targeted NGS to be used for clinical molecular diagnosis in suspected BHDS patients.

Development of an immune-related gene pairs signature for predicting clinical outcome in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the main pathological subtype of Non-small cell lung cancer. We downloaded the gene expression profile and immune-related gene set from the TCGA and ImmPort database, respectively, to establish immune-related gene pairs (IRGPs). Then, IRGPs were subjected to univariate Cox regression analysis, LASSO regression analysis, and multivariable Cox regression analysis to screen and develop an IRGPs signature. The receiver operating characteristic curve (ROC) was applied for evaluating the predicting accuracy of this signature by calculating the area under ROC (AUC) and data from the GEO set was used to validate this signature. The relationship of 22 tumor-infiltrating immune cells (TIICs) to the immune risk score was also investigated. An IRGPs signature with 8 IRGPs was constructed. The AUC for 1- and 3-year overall survival in the TCGA set was 0.867 and 0.870, respectively. Similar results were observed in the AUCs of GEO set 1, 2 and 3 (GEO set 1 [1-year: 0.819; 3-year: 0.803]; GEO set 2 [1-year: 0.834; 3-year: 0.870]; GEO set 3 [1-year: 0.955; 3-year: 0.827]). Survival analysis demonstrated high-risk LUAD patients exhibited poorer prognosis. The multivariable Cox regression indicated that the risk score was an independent prognostic factor. The immune risk score was highly associated with several TIICs (Plasma cells, memory B cells, resting memory CD4 T cells, and activated NK cells). We developed a novel IRGPs signature for predicting 1- and 3- year overall survival in LUAD, which would be helpful for prognosis assessment of LUAD.

The effectiveness of preemptive analgesia for relieving postoperative pain after video-assisted thoracoscopic surgery (VATS): a prospective, non-randomized controlled trial.

BACKGROUND: The effectiveness of preemptive analgesia (PA) for relieving postoperative pain and reducing the side effects of analgesics following video-assisted thoracoscopic surgery (VATS) has not yet been determined. This study intends to test the clinical application value of PA in the perioperative period of VATS. METHODS: From January 2018 to August 2018, we divided patients who underwent VATS in our hospital into a trial group (PA group) and a control group (traditional analgesia group, TA group). The PA group received a PA program, and the TA group was administered a conventional postoperative analgesia scheme. We compared the two groups according to the intensity of postoperative pain using the numeric rating scale (NRS), the incidence rate of analgesic drug-related adverse reactions, and the severity of stress-induced inflammation. RESULTS: One hundred five cases from the PA group, and 80 cases from the TA group were included in the analysis. There were no significant differences between the two groups in baseline characteristics (P>0.05). The PA group had a lower incidence rate of side effects from the analgesics compared to the TA group, and there was a statistical difference at 48 and 72 hours after surgery (P<0.05). The PA group had a slightly lower score than the TA group for postoperative resting pain. However, this difference was not statistically significant (P>0.05). The motion pain NRS score of the PA group was lower than the TA group, and although there were no significant differences at 4, 24, and 48 hours (P>0.05), there was a statistically significant difference at 72 hours (P<0.05). In the subset of patients with motion pain NRS ≥3 points, the PA group was marginally higher than the TA group at 4 hours (P>0.05) but was lower than the TA group at 24, 48, and 72 hours, with a statistically significant difference at 24 and 72 hours (P<0.05). There were no statistically significant differences in perioperative stress indexes between the two groups (P>0.05). CONCLUSIONS: PA can relieve postoperative pain following VATS and reduce the incidence rate of analgesic drug-related adverse effects.

The removal of uranium using novel temperature sensitive urea-formaldehyde resin: adsorption and fast regeneration.

A novel adsorbent of temperature sensitive urea-formaldehyde (TS-UF) resin was synthesized by base/acid two-step synthetic strategy with low formaldehyde/urea mole ratio of 0.8. The sorption kinetics of TS-UF resin obeys the pseudo-second-order model, and the adsorption is an endothermic process. The Langmuir model can well describe the sorption isotherms, through which the Qmax is calculated to be 99.2 mg/g for uranium (VI) at pH 6.0 and T = 298 K. The characterized results show that the functional groups -NH- and -CH2OH in TS-UF resin have been involved in uranium sorption via chemical interaction. The temperature sensitive property of TS-UF resin significantly accelerates the regeneration of TS-UF resin, which can be fast regenerated within 15 min at its low critical solution temperature 333 K and exhibits high removal efficiency of uranium (VI) (>90%) over 5 cycles. Therefore, TS-UF resin can be as a promising sorbent for the uranium (VI) removal from wastewater due to its low-cost, easy-fabrication, high-efficiency and fast regeneration. This work can not only boost the exploration of novel adsorbent materials, but also promote the investigations of the regeneration and reusability of adsorbents.

FLCN-regulated miRNAs suppressed reparative response in cells and pulmonary lesions of Birt-Hogg-Dubé syndrome.

BACKGROUND: Birt-Hogg-Dubé Syndrome (BHDS) characterised by skin fibrofolliculomas, kidney tumour and pulmonary cysts/pneumothorax is caused by folliculin (FLCN) germline mutations. The pathology of both neoplasia and focused tissue loss of BHDS strongly features tissue-specific behaviour of the gene. Isolated cysts/pneumothorax is the most frequent atypical presentation of BHDS and often misdiagnosed as primary spontaneous pneumothorax (PSP). Deferential diagnosis of BHDS with isolated pulmonary presentation (PSP-BHD) from PSP is essential in lifelong surveillance for developing renal cell carcinoma. METHODS: The expression profiles of microRNAs (miRNAs) in cystic lesions of PSP-BHD and PSP were determined via microarray. The selected upregulated miRNAs were further confirmed in the plasma of an expanded cohort of PSP-BHD patients by reverse transcription quantitative PCR (RT-qPCR). Their diagnostic accuracy was evaluated. Moreover, the cellular functions and targeted signalling pathways of FLCN-regulated miRNAs were assessed in various cell lines and in the lesion tissue contexts. RESULTS: Cystic lesions of PSP-BHD and PSP showed different miRNAs profiles with a significant upregulation of miR-424-5p and let-7d-5p in PSP-BHD. The combination of the two effectively predicted BHDS patients. In vitro studies revealed a suppressive effect of FLCN on miR-424-5p and let-7d-5p expressions specifically in lung epithelial cells. The ectopic miRNAs triggered epithelial apoptosis and epithelial transition of mesenchymal cells and suppressed the reparative responses in cells and tissues with FLCN deficiency. CONCLUSION: The upregulation of miR-424-5p and let-7d-5p by FLCN deficiency occurred in epithelial cells and marked the PSP-BHD condition, which contributed to a focused degenerative pathology in the lung of PSP-BHD patients.

An atrial septal aneurysm with an organized thrombus in an asymptomatic patient: A case report.

INTRODUCTION: An atrial septal aneurysm (ASA) is a rare congenital cardiac deformity characterized by interatrial septum protruding into atria forming a saccular structure. PATIENT CONCERNS: In our case, a 42-year-old female patient presented to our hospital complained of palpitation. DIAGNOSIS: Transthoracic echocardiography detected a 3.4 × 3.4 cm circular mass attached to the interatrial septum in right atrium complicated with a 6 mm secundum atrial septal defects (ASD). INTERVENTIONS: The patient received a cardiopulmonary bypass surgery to remove the mass and close the ASD. OUTCOMES: The mass turned out to be an organized thrombus with calcium deposition and fibrinoid necrosis. CONCLUSION: ASA is a potential location of atrial thrombus because of the stagnation of blood. Systemic embolism events are the main complications of ASA. Surgery or anticoagulation is both recommended in patients with ASA with thrombus.