The causality between systemic inflammatory regulators and chronic respiratory diseases: A bidirectional Mendelian-randomization study.

INTRODUCTION: Accumulative evidence suggests the associations between systemic inflammatory regulators and chronic respiratory diseases (CRDs). However, the intrinsic causation remains implicit. Therefore, this study aimed to examine causative associations by mendelian randomization (MR) and to identify valuable active factors. METHODS: Based on data from the GWAS database, we performed MR analyses of 41 serum cytokines from 8,293 Finnish and European descent cohorts from GBMI and UKBB for five major CRDs. We mainly applied inverse variance weighted regression, supplemented by MR-Egger regression, weighted median, maximum likelihood, weighted mode, and simple mode algorithms. Moreover, sensitivity analyses were conducted using Cochrane's Q test, MR-Egger intercept, MR-PRESSO Global test and MR-Steiger filtering. Eventually, the consistency of MR results was assessed by leave-one-out. RESULTS: Our results suggest that 12 genetically predicted systemic inflammatory regulators probably participate in the progression of CRDs, including four risk factors (IL-1RA, IL-4, MIP-1A, PDGF-BB) and one protective factor (IL-6) in IPF, two protective factors (SCF, SDF-1A) in COPD, and two protective factors (SCF, SDF-1A) in asthma, two protective factors (GROA, IL-2RA) were also included in asthma, whereas only one factor (HGF) was protective against bronchiectasis. Additionally, two protective factors (FGF-BASIC, G-CSF) were identified in sarcoidosis. Sensitivity analyses showed no horizontal pleiotropy and significant heterogeneity. Finally, based on the findings of inverse MR analysis, no inverse causal association was uncovered, confirming the robustness of results. CONCLUSION: Our study unearths potential associations between systemic inflammatory modulators and common CRDs, providing new insights for inflammation-mediated CRD prevention and therapeutic approaches.

Exploring the causal relationship between immune cells and idiopathic pulmonary fibrosis: a bi-directional Mendelian randomization study.

BACKGROUND: The potential pathogenic mechanism of idiopathic pulmonary fibrosis is widely recognized to involve immune dysregulation. However, the current pool of studies has yet to establish a unanimous agreement regarding the correlation between various types of immune cells and IPF. METHODS: By conducting a two-sample Mendelian randomization analysis using publicly available genetic data, the study examined the causal relationship between IPF and 731 immune cells. To ensure the reliability of the results, combined sensitivity analyses and inverse Mendelian analyses were conducted. Moreover, within subgroups, multivariate Mendelian randomization analyses were utilized to investigate the autonomous causal connection between immune cell characteristics and IPF. RESULTS: After adjusting for false discovery rate, it was discovered that 20 immunophenotypes exhibited a significant association with IPF. After subgrouping for multivariate Mendelian randomization analysis, there were six immunophenotypes that remained significantly associated with IPF. These included CD33 + HLA DR + CD14dim (OR = 0.96, 95% CI 0.93-0.99, P = 0.033), HLA DR + NK (OR = 0.92, 95% CI 0.85-0.98, P = 0.017), CD39 + CD8 + T cell %T cell (OR = 0.93, 95% CI 0.88-0.99, P = 0.024), CD3 on activated & secreting Treg (OR = 0.91, 95% CI 0.84-0.98, P = 0.026), PDL-1 on CD14- CD16 + monocyte (OR = 0.89, 95% CI 0.84-0.95, P = 8 × 10-4), and CD45 on CD33 + HLA DR + CD14- (OR = 1.08, 95% CI 1.01-1.15, P = 0.011). CONCLUSION: Our study reveals a noteworthy association between IPF and various immune cells, providing valuable insights for clinical research and aiding the advancement of immunologically-based therapeutic strategies.

Detection of Green Asparagus in Complex Environments Based on the Improved YOLOv5 Algorithm.

An improved YOLOv5 algorithm for the efficient recognition and detection of asparagus with a high accuracy in complex environments was proposed in this study to realize the intelligent machine harvesting of green asparagus. The coordinate attention (CA) mechanism was added to the backbone feature extraction network, which focused more attention on the growth characteristics of asparagus. In the neck part of the algorithm, PANet was replaced with BiFPN, which enhanced the feature propagation and reuse. At the same time, a dataset of asparagus in complex environments under different weather conditions was constructed, and the performance variations of the models with distinct attention mechanisms and feature fusion networks were compared through experiments. Experimental results showed that the mAP@0.5 of the improved YOLOv5 model increased by 4.22% and reached 98.69%, compared with the YOLOv5 prototype network. Thus, the improved YOLOv5 algorithm can effectively detect asparagus and provide technical support for intelligent machine harvesting of asparagus in different weather conditions and complex environments.

HLA class II molecule HLA-DRA identifies immuno-hot tumors and predicts the therapeutic response to anti-PD-1 immunotherapy in NSCLC.

BACKGROUND: Immune checkpoint blockade (ICB) only works well for a certain subset of patients with non-small cell lung cancer (NSCLC). Therefore, biomarkers for patient stratification are desired, which can suggest the most beneficial treatment. METHODS: In this study, three datasets (GSE126044, GSE135222, and GSE136961) of immunotherapy from the Gene Expression Omnibus (GEO) database were analyzed, and seven intersected candidates were extracted as potential biomarkers for ICB followed by validation with The Cancer Genome Atlas (TCGA) dataset and the in-house cohort data. RESULTS: Among these candidates, we found that human leukocyte antigen-DR alpha (HLA-DRA) was downregulated in NSCLC tissues and both tumor and immune cells expressed HLA-DRA. In addition, HLA-DRA was associated with an inflamed tumor microenvironment (TME) and could predict the response to ICB in NSCLC. Moreover, we validated the predictive value of HLA-DRA in immunotherapy using an in-house cohort. Furthermore, HLA-DRA was related to the features of inflamed TME in not only NSCLC but also in most cancer types. CONCLUSION: Overall, HLA-DRA could be a promising biomarker for guiding ICB in NSCLC.

Let-7 mediated airway remodelling in chronic obstructive pulmonary disease via the regulation of IL-6.

BACKGROUND: Myofibroblast differentiation and extracellular matrix (ECM) deposition are observed in chronic obstructive pulmonary disease (COPD). However, the mechanisms of regulation of myofibroblast differentiation remain unclear. MATERIALS AND METHODS: We detected let-7 levels in peripheral lung tissues, serum and primary bronchial epithelial cells of COPD patients and cigarette smoke (CS)-exposed mice. IL-6 mRNA was explored in lung tissues of COPD patients and CS-exposed mice. IL-6 protein was detected in cell supernatant from primary epithelial cells by ELISA. We confirmed the regulatory effect of let-7 on IL-6 by luciferase reporter assay. Western blotting assay was used to determine the expression of α-SMA, E-cadherin and collagen I. In vitro, cell study was performed to demonstrate the role of let-7 in myofibroblast differentiation and ECM deposition. RESULTS: Low expression of let-7 was observed in COPD patients, CS-exposed mice and CS extract (CSE)-treated human bronchial epithelial (HBE) cells. Increased IL-6 was found in COPD patients, CS-exposed mice and CSE-treated HBE cells. Let-7 targets and silences IL-6 protein coding genes through binding to 3' untranslated region (UTR) of IL-6. Normal or CSE-treated HBE cells were co-cultured with human embryonic lung fibroblasts (MRC-5 cells). Reduction of let-7 in HBE cells caused myofibroblast differentiation and ECM deposition, while increase of let-7 mimics decreased myofibroblast differentiation phenotype and ECM deposition. CONCLUSION: We demonstrate that CS reduced let-7 expression in COPD and, further, identify let-7 as a regulator of myofibroblast differentiation through the regulation of IL-6, which has potential value for diagnosis and treatment of COPD.

Isolation and Retrieval of Extracellular Vesicles for Liquid Biopsy of Malignant Ground-Glass Opacity.

Extracellular vesicles (EVs) are cell-released vesicles of submicrometer size. EVs contain a tissue-specific signature wherein a variety of proteins and nucleic acids are selectively packaged. Recent studies validate that EVs can be used for cancer diagnostics, staging, and treatment monitoring. EV-related clinical translation requires effective EV isolation as a prerequisite. However, lengthy procedures, low yield, low throughput, and high levels of contaminants disqualify the existing isolation approaches for large-scale clinical use. Hence, new approaches for rapid, efficient, and low-cost isolation of EVs in high purity for flexible analyses of the diverse contents in real-world clinical settings are highly desired yet are currently unavailable. Here, we report the effective use of heparin/polymer-coated microspheres (HPM) for EV isolation and retrieval. Approximately 81% of EVs can be isolated from plasma in 1 h with depletion of ∼99.5% plasma protein and nucleic acid contaminants, and 72% of isolated EVs can be retrieved with saline in 5 min for various cargo analyses. This approach was further validated with clinical samples derived from patients with malignant ground-glass opacity (GGO). In eight patients, the mutation concordance between EV DNA and tissue DNA is 39.8%. The prevalence and mutation count of EGFR, TP53, and NF1 are higher than those of other oncogenes and antioncogenes that are intensely associated with lung adenocarcinoma. Moreover, different mutation prevalence and patterns between smokers and nonsmokers can be observed. Our findings suggest that the combination of HPM assay and targeted sequencing of EV DNA could be translated in the differential diagnosis of malignant GGO with short turnaround time.

Epidermal Growth Factor Receptor Mutations in Resectable Non-Small Cell Lung Cancer Patients and their Potential Role in the Immune Landscape.

BACKGROUND The epidermal growth factor receptor (EGFR) is a therapeutic target for non-small cell lung cancer (NSCLC), but knowledge on gene mutations that contribute to NSCLC development and persistence is lacking. In this study, we investigated genetic variations in EGFR and their association with the clinical and pathological factors of NSCLC. MATERIAL AND METHODS Clinical cases (331 patients) and The Cancer Genome Atlas (TCGA) cases (1040 patients) were selected and analyzed using the refractory mutation systems cBioPortal and the Tumor Immune Estimation Resource (TIMER). RESULTS EGFR mutation frequencies were 54.4% (180 of 331 patients) and 8.0% (83 of 1040 patients) in the clinical and TCGA cohorts, respectively. EGFR mutations were strongly associated with smoking and pathology (P≤0.05) in the clinical cohort, and with gender, smoking, and pathology (P=0.001, P<0.001, and P<0.001, respectively) in TCGA cohort. In cases of lung squamous carcinoma (LUSC), EGFR was overexpressed as a result of DNA amplification, but this amplified expression showed no association with the overall survival (OS) or progression-free survival of LUSC patients. EGFR gene alterations were, however, associated with worse OS in lung adenocarcinoma (LUAD) patients. Immune cell infiltrates from LUAD and LUSC tumors differed according to EGFR expression. EGFR mutations resulted in a decline of immune infiltration or a lack of infiltrating immune cells in the NSCLC microenvironment. CONCLUSIONS Mutational profiles of the EGFR in NSCLC patients provide useful information for the use of tyrosine kinase inhibitors for adjuvant or neoadjuvant therapy and immunotherapy.

Genetic variants at 8q24 are associated with risk of esophageal squamous cell carcinoma in a Chinese population.

Esophageal cancer and gastric cancer have shared risk factors and inherited susceptibility. Recent genome-wide association studies have identified multiple genetic loci associated with gastric cancer risk, which may also involve in the development of esophageal cancer. Herein, we evaluated the relationship of gastric cancer risk-related variants at 1q22, 3q13.3, 5p13.1, and 8q24 with the risk of esophageal squamous cell carcinoma (ESCC) in a Chinese population with a case-control study (2139 cases and 2273 controls). We found that the T allele of rs2294008, an intronic variant of the PSCA gene at 8q24 that was previously associated with an increased risk of gastric cancer, was inversely associated with a decreased risk of ESCC (odds ratio = 0.90; 95% confidence interval, 0.81-0.99; P = 0.034). Of interest, the association of rs2294008 with ESCC was consistent with that observed in esophageal adenocarcinoma and ESCC in Caucasian populations. However, no significant associations were observed for the other three variants at 1q22 (rs4072037), 3q13.31 (rs9841504), and 5p13.1 (rs13361707). Our findings suggest that the susceptibility locus of PSCA at 8q24 may be a double-edged sword, as modulator between the carcinogenesis processes of stomach and esophagus.

DNA methylation analysis in plasma for early diagnosis in lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) represents the most prevalent type of lung cancer. SHOX2 and RASSF1A methylation have been identified as important biomarkers for diagnosis and prognosis of lung cancer. Bronchoalveolar lavage fluid (BALF) exhibits good specificity and sensitivity in diagnosing pulmonary diseases, but its acquisition is challenging and may cause discomfort to patients. In clinical, plasma samples are more convenient to obtain than BALF; however, there is little research on the concurrent detection of SHOX2 and RASSF1A methylation in plasma. This study aims to assess the diagnostic value of a combined promoter methylation assay for SHOX2 and RASSF1A in early-stage LUAD using plasma samples. METHODS: BALF and blood samples were obtained from 36 early-stage LUAD patients, with a control group of nineteen non-tumor individuals. The promoter methylation levels of SHOX2 and RASSF1A in all subjects were assessed using the human SHOX2 and RASSF1A gene methylation kit. RESULTS: The methylation detection rate of SHOX2 and RASSF1A in plasma was 61.11%, slightly lower than that in BALF (66.7%). The Chi-square test revealed no significant difference in the methylation rate between BALF and plasma (P > 0.05). The area under the receiver operating characteristic (ROC) curve analysis for blood was 0.806 (95% CI, 0.677 to 0.900), while for BALF it was 0.781 (95% CI, 0.649 to 0.881). Additionally, we conducted an analysis on the correlation between SHOX2 and RASSF1A methylation levels in plasma with gender, age, tumor differentiation, pathologic classification, and other clinicopathological variables; however, no significant correlations were observed. CONCLUSIONS: Measurement of SHOX2 and RASSF1A methylation for early diagnosis of LUAD can be achieved with high sensitivity and specificity by using plasma as a substitute for BALF samples.

Therapeutic Drug Monitoring of Linezolid in Drug-Resistant Tuberculosis Patients: Clinical Factors and Hematological Toxicities.

Purpose: Previous studies have indicated that the development of severe adverse events is associated with linezolid peak concentration (Cmax), but the factors affecting linezolid Cmax and evidences on therapeutic drug monitoring to anticipate toxicity in drug-resistant tuberculosis (DR-TB) patients have not been clarified clearly. This study aimed to explore the factors influencing linezolid Cmax and investigate the association between linezolid concentration and hematological toxicity. Patients and Methods: This study included patients with drug-resistant tuberculosis treated with linezolid from January 2022 to September 2023. We analyzed the factors affecting linezolid Cmax using chi-squared and binary logistic regression. The diagnostic utility of linezolid Cmax in predicting hematological toxicity was evaluated using receiver operating characteristic (ROC) analysis. Results: A total of 76 patients were enrolled in the study. 63.20% met the standard rates for linezolid Cmax. Age (P=0.036), weight (P=0.0016), and creatinine clearance (P=0.0223) significantly correlated with the Cmax. Hematological toxicity was observed in 46.05% (35/76) of patients, characterized by thrombocytopenia (31.58%, 24/76), anemia (6.58%, 5/76), and leukopenia (21.05%, 16/76). ROC curve analysis confirmed the predictive value of linezolid Cmax for thrombocytopenia with an area under curve of 0.728. Conclusion: Suboptimal linezolid Cmax was prevalent among patients with DR-TB, with age, weight, and renal function emerging as influential factors. Elevated linezolid Cmax increases the risk of thrombocytopenia. Meticulous monitoring of linezolid Cmax is imperative during anti-DR-TB therapy to tailor treatment and mitigate hematological toxicity.

The diagnostic potential role of thioredoxin reductase and TXNRD1 in early lung adenocarcinoma: A cohort study.

Background: Lung adenocarcinoma (LUAD) is the primary form of lung cancer, yet the reliable biomarkers for early diagnosis remain insufficient. Thioredoxin reductase (TrxR) is strongly linked to the occurrence, development, and drug resistance of lung cancer, making it a potential biomarker. However, further research is required to assess its diagnostic value in LUAD. Methods: A retrospective analysis was performed on patients who underwent pulmonary nodule resection at our center from 2018 to 2022. Clinical data, including preoperative TrxR levels, imaging, and laboratory characteristics, were identified as study variables. Two prediction models were constructed using multiple logistic regression, and their prediction performance was evaluated comprehensively. Besides, bioinformatics analyses of TrxR coding genes including differential expression, functional enrichment, immune infiltration, drug sensitivity, and single-cell landscape were performed based on TCGA database, which were subsequently validated by Human Protein Atlas. Results: A total of 506 eligible patients (72 benign lesions, 77 AISs, 185 MIAs and 172 IACs) were identified in the clinical cohort. Two TrxR-based models were developed, which were able to distinguish between benign and malignant pulmonary nodules, as well as pathological subtypes of LUAD, respectively. The models exhibited good predictive ability with all AUC values ranging from 0.7 to 0.9. Based on calibration curves and clinical decision analysis, the nomogram models showed high reliability. Functional analysis indicated that TXNRD1 primarily participated in cell cycle and lipid metabolism. Immune infiltration analysis showed that TXNRD1 has a strong association with immune cells and could impact immunotherapy. Then, we identified small molecular compounds that inhibit TXNRD1 and confirmed TXNRD1 expression by single-cell landscape and immunohistochemistry. Conclusion: This study validated the diagnostic value of TrxR and TXNRD1 in clinical cohorts and transcriptional data, respectively. TrxR and TXNRD1 could be used in the risk diagnosis of early LUAD and facilitate personalized treatment strategies.

An Anthropomorphic Diagnosis System of Pulmonary Nodules using Weak Annotation-Based Deep Learning.

Purpose: To develop an anthropomorphic diagnosis system of pulmonary nodules (PN) based on Deep learning (DL) that is trained by weak annotation data and has comparable performance to full-annotation based diagnosis systems. Methods: The proposed system uses deep learning (DL) models to classify PNs (benign vs. malignant) with weak annotations, which eliminates the need for time-consuming and labor-intensive manual annotations of PNs. Moreover, the PN classification networks, augmented with handcrafted shape features acquired through the ball-scale transform technique, demonstrate capability to differentiate PNs with diverse labels, including pure ground-glass opacities, part-solid nodules, and solid nodules. Results: The experiments were conducted on two lung CT datasets: (1) public LIDC-IDRI dataset with 1,018 subjects, (2) In-house dataset with 2740 subjects. Through 5-fold cross-validation on two datasets, the system achieved the following results: (1) an Area Under Curve (AUC) of 0.938 for PN localization and an AUC of 0.912 for PN differential diagnosis on the LIDC-IDRI dataset of 814 testing cases, (2) an AUC of 0.943 for PN localization and an AUC of 0.815 for PN differential diagnosis on the in-house dataset of 822 testing cases. These results demonstrate comparable performance to full annotation-based diagnosis systems. Conclusions: Our system can efficiently localize and differentially diagnose PNs even in resource-limited environments with good robustness across different grade and morphology sub-groups in the presence of deviations due to the size, shape, and texture of the nodule, indicating its potential for future clinical translation. Summary: An anthropomorphic diagnosis system of pulmonary nodules (PN) based on deep learning and weak annotation was found to achieve comparable performance to full-annotation dataset-based diagnosis systems, significantly reducing the time and the cost associated with the annotation. Key Points: A fully automatic system for the diagnosis of PN in CT scans using a suitable deep learning model and weak annotations was developed to achieve comparable performance (AUC = 0.938 for PN localization, AUC = 0.912 for PN differential diagnosis) with the full-annotation based deep learning models, reducing around 30%∼80% of annotation time for the experts.The integration of the hand-crafted feature acquired from human experts (natural intelligence) into the deep learning networks and the fusion of the classification results of multi-scale networks can efficiently improve the PN classification performance across different diameters and sub-groups of the nodule.

Successful lung autotransplantation for central non-small-cell lung cancer: report of a case.

Non-small-cell lung cancer (NSCLC) confined to the lung is generally treated by surgical resection. The extent of resection is determined by the location of the tumor and the patient's pulmonary function. This report presents a successful lung autotransplantation in a man with NSCLC that could not tolerate pneumonectomy or sleeve lobectomy. Right upper and middle bilobectomies were performed, the right lower lobe was resected and retrograde perfusion of Raffinose low-potassium dextran solution (4 °C) was administered. The isolated lower lobe was reimplanted by anastomosis of the bronchus, pulmonary artery, and vein. The patient was cancer-free 1 year after the surgery. Lung autotransplantation can therefore be successfully performed for selected patients with central NSCLC.

[Early cardiovascular complications post lung transplantation].

OBJECTIVE: To observe the early cardiovascular complications of patients underwent lung transplantation. METHODS: The clinical records of 73 patients who underwent lung transplantation in Wuxi People's Hospital from September 2002 to September of 2010 were retrospectively analyzed. All patients were transferred to intensive care unit (ICU) after lung transplantation, received invasive monitoring (PICCO), mechanical ventilation, immunosuppressive therapy and measures to prevent ischemic reperfusion injury. The early cardiovascular complications after lung transplantation up to discharge from hospital were observed. RESULTS: The postoperative mortality was 20.5% (15/73) within 30 days after surgery. Five patients died of cardiovascular reasons including 2 cases of pulmonary embolism and 3 cases of ventricular fibrillation. Cardiovascular complications during the early post-operation period included: paroxysmal atrial fibrillation (19 cases, 26.0%) and persist atrial fibrillation (1 case, 1.4%); atrial fibrillation and atrial flutter in 3 cases and persistent atrial flutter in 1 patient; ventricular fibrillation (3 cases, 4.1%); paroxysmal supraventricular tachycardia (3 cases, 4.1%); ventricular tachycardia (2 cases, 2.7%); bundle branch block (8 cases, 11.0%); intraventricular block(4 cases, 5.5%); left ventricular heart failure(4 cases, 5.5%), right heart failure(6 cases, 8.2%); pulmonary embolism (2 cases, 2.7%), deep venous thrombosis (1 case, 1.4%). CONCLUSIONS: Atrial fibrillation is the most common cardiovascular complication post lung transplantation. Pulmonary embolism and ventricular fibrillation are not common but related with high mortality rate post lung transplantation.

Preparation of low molecular weight polysaccharides from Tremella fuciformis by ultrasonic-assisted H2O2-Vc method: Structural characteristics, in vivo antioxidant activity and stress resistance.

Different methods were used to degrade Tremella fuciformis polysaccharides (TFP) and prepare low molecular weight polysaccharides of Tremella fuciformis (TFLP) to improve their bioavailability. It was found that the TFLP prepared by ultrasonic-assisted H2O2-Vc method showed the highest level of antioxidant activity and stress resistance in C. elegans. The structural characteristics, in vivo antioxidant and stress resistance of TFLP-1 were evaluated after isolation and purification of TFLP, it was found that TFLP-1 was an acid polysaccharide with a molecular weight of 75770 Da, which mainly composed of mannose. Meanwhile, it could regulate the antioxidant activity and stress resistance in C. elegans by upregulating the transcription of fat-5, fat-7, acs-2, glp-1, hsf-1, hsp-1, mtl-1, nhr-49, skn-1 and sod-3 mRNA. The improvement effects were closely related to the significant regulation of galactose metabolism, alpha linolenic acid metabolism, and pantothenate and CoA biosynthesis metabolic pathways. These results provided insights into the high value application of Tremella fuciformis in the food industry and the development of antioxidant related functional foods.

Unilateral biportal endoscopic foraminotomy and diskectomy combined with piezosurgery for treating cervical spondylotic radiculopathy with neuropathic radicular pain.

Objective: Unilateral biportal endoscopy (UBE) represents a relatively recent development in minimally invasive spine surgery. This study aimed to evaluate the efficacy and safety of UBE foraminotomy and diskectomy combined with piezosurgery for treating cervical spondylotic radiculopathy (CSR) with neuropathic radicular pain. Methods: We retrospectively analyzed the outcomes in 12 patients with CSR who underwent UBE foraminotomy and diskectomy combined with piezosurgery. The intraoperative blood loss, operative time, visual analog scale (VAS) scores for the neck and arm, neck disability index (NDI) scores, and complications were recorded. Results: Postoperative VAS scores of the neck and arm and NDI scores were significantly improved. Additionally, a postoperative CT scan revealed adequate enlargement of the cervical canal and nerve root. No specific complications occurred during surgery and the immediate postoperative period. Conclusions: This primary study indicated that the UBE foraminotomy and diskectomy with piezosurgery is a promising technique for treating cervical spondylotic radiculopathy with neuropathic radicular pain.

Clinical utility of tuberculosis RNA in the rapid diagnosis of bone and joint tuberculosis.

OBJECTIVES: To evaluate the diagnostic accuracy of tuberculosis RNA (TB-RNA) for the rapid diagnosis of bone and joint tuberculosis (BJTB). METHODS: We conducted a retrospective study to evaluate the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) of TB-RNA and acid-fast bacillus (AFB) smear against the final clinical diagnosis. RESULTS: A total of 268 patients were included. The overall sensitivity, specificity, PPV, NPV, and AUC of AFB smear for BJTB were 0.7%, 100.0%, 100.0%, 49.3%, and 0.50, respectively, whereas those of TB-RNA were 59.6%, 100.0%, 100.0%, 70.6%, and 0.80, respectively; for cases of confirmed (culture-positive) BJTB, these values were 82.8%, 99.4%, 99.7%, 89.2%, and 0.91, respectively. CONCLUSIONS: The diagnostic accuracy of TB-RNA in the rapid diagnosis of BJTB was relatively good, especially in culture-positive BJTB. The use of TB-RNA could be an effective technique for the rapid diagnosis of BJTB.

Precursors and formation pathways of furfural in sugarcane juice during thermal treatment.

As a potent aromatic compound, furfural may have adverse effects on sugarcane juice quality. In this study, simplified sugarcane juice models containing glucose, fructose and amino acids were used to explore the potential precursors and formation pathways of furfural. The changes of precursors and intermediates involved in furfural formation were quantified. The results indicated that fructose contributed more to furfural formation than glucose. Serine was the main amino acid precursor for furfural formation. Furfural could be generated through 3 pathways in sugarcane juice: 1) Streaker reaction of serine, 2) caramelization of glucose and fructose via 3-deoxyglucosone, 3) formed from reducing sugars (glucose or fructose) and serine via N-(1-Deoxy-d-fructos-1-yl)-l-serine intermediate, which further converted to 3-deoxyglucosone. At the first 10 min, furfural was mainly produced through the caramelization of fructose. Subsequently, furfural was produced in the above three ways. Furfural was more effectively formed by caramelization than Maillard reaction in sugarcane juice.

Establishment and validation of nomograms for predicting survival of lung invasive adenocarcinoma based on the level of pathological differentiation: a SEER cohort-based analysis.

Background: The pathological differentiation of invasive adenocarcinoma (IAC) has been linked closely with epidemiological characteristics and clinical prognosis. However, the current models cannot accurately predict IAC outcomes and the role of pathological differentiation is confused. This study aimed to establish differentiation-specific nomograms to explore the effect of IAC pathological differentiation on overall survival (OS) and cancer-specific survival (CSS). Methods: The data of eligible IAC patients between 1975 and 2019 were collected from the Surveillance, Epidemiology, and End Results (SEER) database, and randomly divided in a ratio of 7:3 into a training cohort and a validation cohort. The associations between pathological differentiation and other clinical characteristics were evaluated using chi-squared test. The OS and CSS analyses were performed using the Kaplan-Meier estimator, and the log-rank test was used for nonparametric group comparisons. Multivariate survival analysis was performed using a Cox proportional hazards regression model. The discrimination, calibration, and clinical performance of nomograms were assessed by area under receiver operating characteristic curve (AUC), calibration plots, and decision curve analysis (DCA). Results: A total of 4,418 IAC patients (1,001 high-differentiation, 1,866 moderate-differentiation, and 1,551 low-differentiation) were identified. Seven risk factors [age, sex, race, tumor-node-metastasis (TNM) stage, tumor size, marital status, and surgery] were screened to construct differentiation-specific nomograms. Subgroup analyses showed that disparate pathological differentiation played distinct roles in prognosis, especially in patients with older age, white race, and higher TNM stage. The AUC of nomograms for OS and CSS in the training cohort were 0.817 and 0.835, while in the validation cohort were 0.784 and 0.813. The calibration curves showed good conformity between the prediction of the nomograms and the actual observations. DCA results indicated that these nomogram models could be used as a supplement to the prediction of the TNM stage. Conclusions: Pathological differentiation should be considered as an independent risk factor for OS and CSS of IAC. Differentiation-specific nomogram models with good discrimination and calibration capacity were developed in the study to predict the OS and CSS in 1-, 3- and 5-year, which could be used predict prognosis and select appropriate treatment options.

The multi-omics analysis identifies a novel cuproptosis-anoikis-related gene signature in prognosis and immune infiltration characterization of lung adenocarcinoma.

Background: Lung adenocarcinoma (LUAD) has emerged as one of the most aggressive lethal cancers. Anoikis serves as programmed apoptosis initiated by the detachment of cells from the extracel-lular matrix. Cuproptosis is distinct from traditional cell death modalities. The above two modes are both closely related to tumor progression, prognosis, and treatment. However, whether they have synergistic effects in LUAD deserves further investigation. Methods: The anoikis-related prognostic genes (ANRGs) co-expressed with cuproptosis-associated genes (CAGs) were screened using correlation analysis, analysis of variance, least absolute shrinkage, and selection operator (LASSO), and COX regression followed by functional analysis, and then LUAD risk score model was constructed. Using consensus clustering, the relationship between different subtypes and clinicopathological features, immune infiltration characteristics, and somatic mutations was analyzed. A nomogram was developed by incorporating clinical information, which provided a prediction of the survival of patients. Finally, a comprehensive analysis of ANRGs was performed and verified by the HPA database. Results: A total of 27 ANRGs associated with cuproptosis were obtained. On this basis, three distinct ANRGs subtypes were identified, and the differences between clinical prognosis and immune infiltration were observed. A risk score model has been constructed by incorporating seven ANRGs signatures (EIF2AK3, IKZF3, ITGAV, OGT, PLK1, TRAF2, XRCC5). A highly reliable nomogram was developed to help formulate treatment strategies based on risk score and the clinicopathological features of LUAD. The seven-gene signature was turned out to be strongly linked to immune cells and validated in single-cell data. Immunohistochemistry proved that all of them are highly expressed in LUAD tissues. Conclusion: This study reveals the potential relationship between cuproptosis-related ANRGs and clinicopathological features, tumor microenvironment (TME), and mutation characteristics, which can be applied for predicting the prognosis of LUAD and help develop individualized treatment strategies.