Sublobectomy and lymph node sampling are adequate for patients with invasive lung adenocarcinoma presenting as pure ground glass nodules.

PURPOSE: In this study, we aimed to investigate the prognosis of invasive lung adenocarcinoma that manifests as pure ground glass nodules (pGGNs) and confirm the effectiveness of sublobectomy and lymph node sampling in patients with pGGN-featured invasive adenocarcinoma (IAC). MATERIALS AND METHODS: We retrospectively enrolled 139 patients with pGGN-featured IAC, who underwent complete resection in two medical institutions between January 2011 and May 2022. Stratification analysis was conducted to ensure balanced baseline characteristics among the patients. The 5-year overall survival (OS) and disease-free survival (DFS) rates were compared between the groups using Kaplan-Meier survival curves and log-rank test. RESULTS: The 5-year OS and DFS rates for patients with IAC presenting as pGGNs after surgery were 96.5% and 100%, respectively. No lymph node metastasis or recurrence was observed in any of the enrolled patients. There was no statistically significant difference in the 5-year OS between patients who underwent lobectomy or sublobectomy, along with lymph node resection or sampling. CONCLUSION: IAC presented as pGGNs exhibited low-grade malignancy and had a relatively good prognosis. Therefore, these patients may be treated with sublobectomy and lymph node sampling.

Trajectories and risk factors of persistent cough after pulmonary resection: A prospective two-center study.

BACKGROUND: Persistent cough is one of the most frequent complications following lung cancer surgery. To promote optimal recovery, we conducted a study to investigate the trajectories of coughing symptoms and their impact on quality of life (QOL), as well as to identify potential risk factors of persistent cough after pulmonary resection (CAP). METHODS: This prospective observational study assessed patients who underwent pulmonary resection for lung tumor at two medical centers in China. Persistent CAP was evaluated before surgery, at discharge, and 1, 3, and 6 months following surgery using visual analog scale (VAS), cough symptom score (CSS), and Leicester Cough Questionnaire in Mandarin Chinese (LCQ-MC). Univariate and multivariate logistic regression analyses were conducted to explore independent risk factors for persistent CAP. RESULTS: Of the 506 enrolled patients, 130 patients were diagnosed with persistent CAP with an incidence of 25.69%. Compared to the noncough group, patients with persistent CAP reported significantly higher VAS (p < 0.001) and CSS scores (p < 0.001) and experienced worse QOL (p < 0.001) for up to 6 months, particularly at 1 month following surgery. Multivariable regression analysis revealed that a duration of anesthesia exceeding 156 min (odds ratio [OR]: 1.847, 95% confidence interval [CI]: 1.156-2.951, p = 0.010) and gastroesophageal acid reflux (GER) (OR: 3.870, 95% CI: 2.376-6.304, p < 0.001) were independent risk factors of persistent CAP. CONCLUSION: Patients who suffer from persistent CAP face a substantial burden and diminished QOL for an extended period compared to noncough patients. Moreover, prolonged duration of anesthesia and postoperative GER are potential risk factors of persistent CAP.

Evaluation of combined pathological responses in primary tumor and lymph nodes following neoadjuvant chemoimmunotherapy in non-small cell lung cancer.

BACKGROUND: Inconsistent pathological responses of tumor and lymph nodes (LNs) were frequently observed in non-small cell lung cancer (NSCLC) receiving neoadjuvant chemoimmunotherapy. However, there is a lack of studies to report the prognostic significance and the relevant clinicopathological factors of tumor-nodal inconsistent responses after neoadjuvant immunotherapy or chemoimmunotherapy. Therefore, this study aimed to depict the inconsistent pathological combined tumor-nodal responses in NSCLC patients after neoadjuvant chemoimmunotherapy as well as the underlying clinical significance. METHODS: A total of 81 node-positive NSCLC patients who underwent neoadjuvant chemoimmunotherapy were eligible for inclusion. Demographic, radiologic, and pathological features of patients were recorded. Patients with pathological complete response of both tumor (ypT(pCR)) and LNs (ypN0) were classified into the combined good responder group and the relevant clinicopathological features were evaluated. The event-free survival (EFS) outcome was analyzed using Kaplan-Meier analysis. RESULTS: The ypN0 and ypT(pCR) rates were 74.1 % and 42.0 %, respectively. A significant correlation was observed between ypT(pCR) and ypN0 (P = 0.003), but inconsistent responses remained. The combined responses of the primary tumor and LNs demonstrated a significant association with the prognosis outcome (P = 0.005). Notably,patients who received at least twice of their infusions of immune checkpoint inhibitors after 15:30 had a worse prognosis (P = 0.015). CONCLUSION: A significant but not absolute correlation was observed between good tumor response and good nodal response in NSCLC patients after neoadjuvant chemoimmunotherapy, but inconsistent responses were also found. The combination of tumor and nodal responses is significantly associated with prognosis and combined good responder can be used as a reliable prognosis predictor.

Investigation on sleep quality and psychological distress in patients with pulmonary nodules.

BACKGROUND: Patients with pulmonary nodules (PNs) often suffer from the psychological burden of their disease and trap in sleep problems. This is insufficiently identified and addressed in clinical practice. The aim of this study was to investigate the psychological distress and sleep quality among PN patients and identify potential risk or protective factors for sleep quality. METHODS: We conducted a cross-sectional study, which included 731 PN patients who visited the thoracic clinic of Guangdong Provincial People's Hospital. Each participant completed a structured questionnaire consisting of demographic characteristics, clinical characteristics, the Hospital Anxiety and Depression Scale (HADS) and the Pittsburgh Sleep Quality Index (PSQI). The reliability of the HADS (Cronbach's α = 0.944) and PSQI (Cronbach's α = 0. 0.757) in this study was satisfactory. RESULTS: A total of 328 patients (44.9%) had PSQI global scores > 5, indicating poor quality of sleep. Age ≥ 50 years (OR 1.88, 95% CI 1.35-2.58; P < 0.001), female (OR 1.56, 95% CI 1.05-2.33; P = 0.028), detection of nodule for 7-12 months (vs for more than 24 months, OR 2.14, 95%CI 1.18-3.89, P = 0.013), anxiety (OR 1.78, 95% CI 1.17-2.71; P = 0.007) and depression (OR 1.84, 95% CI 1.16-2.92; P = 0.010) were independent risk factors for impaired sleep quality. A significant correlation revealed that sleep quality was positively correlated with both anxiety and depression (Spearman r = 0.342, P < 0.001 and Spearman r = 0.314, P < 0.001, respectively). All dimensions of the PSQI scale were significantly decreased in both anxiety group and depression group compared to the psychologically normal group (P < 0.05). CONCLUSIONS: Impaired sleep quality is highly prevalent among patients with PNs and associated with age, gender, time from the date of detection, anxiety and depression. Based on the finding of impaired sleep quality and psychological health, screening for psychological and sleep problems in PN patients will be of great clinical benefit.

Efficient Sample Preparation System for Multi-Omics Analysis via Single Cell Mass Spectrometry.

Mass spectrometry (MS) has become a powerful tool for metabolome, lipidome, and proteome analyses. The efficient analysis of multi-omics in single cells, however, is still challenging in the manipulation of single cells and lack of in-fly cellular digestion and extraction approaches. Here, we present a streamlined strategy for highly efficient and automatic single-cell multi-omics analysis by MS. We developed a 10-pL-level microwell chip for housing individual single cells, whose proteins were found to be digested in 5 min, which is 144 times shorter than traditional bulk digestion. Besides, an automated picoliter extraction system was developed for sampling of metabolites, phospholipids, and proteins in tandem from the same single cell. Also, 2 min MS2 spectra were obtained from 700 pL solution of a single cell sample. In addition, 1391 proteins, phospholipids, and metabolites were detected from one single cell within 10 min. We further analyzed cells digested from cancer tissue samples, achieving up to 40% increase in cell classification accuracy using multi-omics analysis in comparison with single-omics analysis. This automated single-cell MS strategy is highly efficient in analyzing multi-omics information for investigation of cell heterogeneity and phenotyping for biomedical applications.

Dynamic alteration in SULmax predicts early pathological tumor response and short-term prognosis in non-small cell lung cancer treated with neoadjuvant immunochemotherapy.

Introduction: Biomarkers predicting tumor response to neoadjuvant immunochemotherapy in non-small cell lung cancer (NSCLC) are still lacking despite great efforts. We aimed to assess the effectiveness of the immune PET Response Criteria in Solid Tumors via SULmax (iPERCIST-max) in predicting tumor response to neoadjuvant immunochemotherapy and short-term survival in locally advanced NSCLC. Methods: In this prospective cohort study, we calculated SULmax, SULpeak, metabolic tumor volume (MTV), total lesion glycolysis (TLG) and their dynamic percentage changes in a training cohort. We then investigated the correlation between alterations in these parameters and pathological tumor responses. Subsequently, iPERCIST-max defined by the proportional changes in the SULmax response (△SULmax%) was constructed and internally validated using a time-dependent receiver operating characteristic (ROC) curve and the area under the curve (AUC) value. A prospective cohort from the Sun Yat-Sen University Cancer Center (SYSUCC) was also included for external validation. The relationship between the iPERCIST-max responsiveness and event-free survival in the training cohort was also investigated. Results: Fifty-five patients with NSCLC were included in this study from May 2019 to December 2021. Significant alterations in post-treatment SULmax (p < 0.001), SULpeak (p < 0.001), SULmean (p < 0.001), MTV (p < 0.001), TLG (p < 0.001), and tumor size (p < 0.001) were observed compared to baseline values. Significant differences in SULpeak, SULmax, and SULmean between major pathological response (mPR) and non-mPR statuses were observed. The optimal cutoff values of the SULmax response rate were -70.0% and -88.0% using the X-tile software. The univariate and multivariate binary logistic regression showed that iPERCIST-max is the only significant key predictor for mPR status [OR = 84.0, 95% confidence interval (CI): 7.84-900.12, p < 0.001]. The AUC value for iPERCIST-max was 0.896 (95% CI: 0.776-1.000, p < 0.001). Further, external validation showed that the AUC value for iPERCIST-max in the SYSUCC cohort was 0.889 (95% CI: 0.698-1.000, p = 0.05). Significantly better event-free survival (EFS) in iPERCIST-max responsive disease (31.5 months, 95% CI 27.9-35.1) than that in iPERCIST-max unresponsive disease (22.2 months, 95% CI: 17.3-27.1 months, p = 0.024) was observed. Conclusion: iPERCIST-max could better predict both early pathological tumor response and short-term prognosis of NSCLC treated with neoadjuvant immunochemotherapy than commonly used criteria. Furthermore, large-scale prospective studies are required to confirm the generalizability of our findings.

The staging performance of a modified tumor-node-metastasis staging system incorporated with lymphovascular invasion in patients with esophageal squamous cell carcinoma.

Background: Lymphovascular invasion (LVI) is recognized as an unfavorable prognostic factor for many solid tumors. However, its staging value has not been adequately illustrated in esophageal squamous cell carcinoma (ESCC). Methods: The clinicopathologic relevance and prognostic impact of LVI were retrospectively analyzed in 822 patients with surgically treated ESCC. Univariate and multivariate analyses were used to determine the independent prognostic factors. Subgroup analyses stratified by pathological stages, nodal status and invasive depth were conducted using Kaplan-Meier method and log-rank test. Multiple staging models based on overall survival (OS) were constructed using Cox regression and evaluated by Harrell's concordance index (C-index), integrated discrimination improvement (IDI), and net reclassification index (NRI). Results: LVI was detected in 24.6% of ESCC patients, and its prevalence increased with a higher pathological stage (p < 0.001). In multivariate analysis, LVI was found to be an independent prognostic factor for OS [Hazard ratio (HR) = 1.545, 95% CI, 1.201-1.986), and was associated with unfavorable outcomes in stage I to III ESCC, regardless of nodal status and invasive depth. The staging model that incorporated LVI as an independent factor achieved the greatest improvement in accuracy (ΔC-index: 2.9%), and the greatest added value (IDI 2.8%, p < 0.01; NRI 13.7%, p < 0.05) for prediction of OS in ESCC patients. Conclusions: LVI can facilitate further survival stratification in ESCC patients. The adoption of LVI as an independent staging factor in the current cancer staging system should be considered and further validated.

Exploring the psychological profile: a cross-sectional study of 1,185 patients with pulmonary nodules in an outpatient clinic.

Background: The purpose of this study was to identify the potential risk and protective factors of psychological burden in patients with pulmonary nodules (PNs) and to explore how the psychological status of the patients affects their treatment preferences. Methods: In this questionnaire-based study, 1,185 outpatients were evaluated using the Hospital Anxiety and Depression Scale (HADS), and the correlations between psychological burden and patients' sociodemographic and clinical characteristics were assessed. Results: Prevalence of anxiety and depression was 42.1% and 27.0%, respectively, among patients with PNs. Binary logistic regression analysis revealed that age over 60 years old [odds ratio (OR) =0.57; 95% confidence interval (CI): 0.36-0.89], computed tomography (CT) scan due to physical discomfort (OR =1.58; 95% CI: 1.11-2.24), multiple PNs (OR =1.52; 95% CI: 1.20-1.94), family history of malignancy (OR =1.28; 95% CI: 1.01-1.64), and subjective symptoms (OR =1.70; 95% CI: 1.32-2.19) were independently associated with anxiety, while multiple PNs (OR =1.51; 95% CI: 1.15-1.98), subjective symptoms (OR =1.65; 95% CI: 1.23-2.20), and indeterminate nodules (OR =1.91; 95% CI: 1.08-3.40) were independently associated with depression. There was a tendency for patients with anxiety and depression to choose more aggressive management strategies (P<0.001 and P=0.001, respectively). Univariate analysis showed that symptomatic patients (χ2=9.696; P=0.021) and those with progressive nodules (χ2=18.198, P=0.033) chose more aggressive treatment strategies. Conclusions: Anxiety and depression are common in patients with PNs, which might result in nonnegligible overtreatment. Presence of subjective symptoms can significantly exacerbate psychological burden and influence treatment preference. Taking psychological factors into consideration in the outpatient clinic may facilitate patient-centered communication and promote judicious decision-making.

Handheld Mass Spectrometer with Intelligent Adaptability for On-Site and Point-of-Care Analysis.

The development of miniature mass spectrometry (MS) systems with simple analysis procedures is important for the transition of applying MS analysis outside traditional analytical laboratories. Here, we present Mini 14, a handheld MS instrument with disposable sample cartridges designed based on the ambient ionization concept for intrasurgical tissue analysis and surface analysis. The instrumentation architecture consists of a single-stage vacuum chamber with a discontinuous atmospheric interface and a linear ion trap. A major effort in this study for technical advancement is on making handheld MS systems capable of automatically adapting to complex conditions for in-field analysis. Machine learning is used to establish the model for autocorrecting the mass offsets in the mass scale due to temperature variations and a new strategy is developed to extend the dynamic concentration range for analysis. Mini 14 weighs 12 kg and can operate on battery power for more than 3 h. The mass range exceeds m/z 2000, and the full peak width at half-maximum is Δm/z 0.4 at a scanning speed of 700 Th/s. The direct analysis of human brain tissue for identifying glioma associated with isocitrate dehydrogenase mutations has been achieved and a limit of detection of 5 ng/mL has been obtained for analyzing illicit drugs in blood.

Effect of Acetylene Links on Electronic and Optical Properties of Semiconducting Graphynes.

The family of graphynes, novel two-dimensional semiconductors with various and fascinating chemical and physical properties, has attracted great interest from both scientific and industrial communities. Currently, the focus is on graphdiyne or graphyne-2. In this work, we systematically study the effect of acetylene, i.e., carbon-carbon triple bond, links on the electronic and optical properties of a series of graphynes (graphyne-n, where n = 1-5, the number of acetylene bonds) using ab initio calculations. We find an even-odd pattern, i.e., n = 1, 3, 5 and n = 2, 4 having different features, which has not been discovered in studying graphyne or graphdiyne alone. It is found that as the number of acetylene bonds increases, the electron effective mass increases continuously in the low-energy range because of the flatter conduction band induced by the longer acetylene links. Meanwhile, longer acetylene links result in a larger red shift of the imaginary part of the dielectric function, loss function, and extinction coefficient. In this work, we propose an effective method to tune and manipulate both the electronic and optical properties of graphynes for the applications in optoelectronic devices and photochemical catalysis.

On-Demand Mass Spectrometry Analysis by Miniature Mass Spectrometer.

Electrospray ionization (ESI) has become a powerful tool for the analysis of biomolecules by mass spectrometry (MS). The process of ESI is difficult to control, and side reactions such as electrochemical reactions can occur during the ESI process because of the high voltages applied. Herein, a novel on-demand MS analysis method was developed based on discontinuous ion injection-induced ESI on a miniature MS system. Highly efficient ionization was enabled under low voltages (<300 V) using a discontinuous atmospheric pressure interface. On-demand ionization showed comparable sensitivity with regular nanoESI for the analyses of a series of compounds. It was found to be softer than regular ESI or nanoESI methods for ionization of proteins such as myoglobin and cytochrome C. As the ionization finished as soon as the interface was closed, the sample consumption was observed to reduce significantly for MS analysis, allowing single-cell analysis with multiple MS and MS/MS measurements.

Prevalence and dynamic characteristics of generalized joint hypermobility in college students.

BACKGROUND: Generalized joint hypermobility (GJH) is a common, but often ignored, condition characterized by general joint laxity, which is reported to increase one's risk of anterior cruciate ligament (ACL) injury and osteoarthritis. Nevertheless, it is not clearly learned in the prevalence and dynamic characteristics in college students. RESEARCH QUESTION: Is the active motion stability in the six-degree-of-freedom (6DOF) kinematics of the knee joint of people with GJH poorer than that of others? METHODS: This is a cross-sectional study. A population of 489 college students was recruited who was divided into two groups: a GJH group (Beighton score ≥ 4, n = 54) and a normal group (Beighton score < 4, n = 435). A paper questionnaire with questions about the participants' demographic characteristics and musculoskeletal disorder symptoms was collected. A three-dimensional gait analysis system was used to collect the participants' knee joint kinematic parameters during treadmill walking. Variables were evaluated using independent t-tests and Wilcoxon signed-rank tests. RESULTS: The prevalence of GJH was found to be 11.0 % among college students. Participants with GJH exhibited a greater active range of motions in the anterior/posterior translation than the normal (P =  0.026). Participants with GJH exhibited greater flexion at the end of the terminal stance (P = 0.039) and greater anterior translation of the tibia during almost the whole gait period than the normal group (P＜0.05) during the treadmill gait. A greater external angle was found in GJH group during the periods of middle stance (P = 0.008). SIGNIFICANCE: GJH with a prevalence of 11.0 % among college students should be paid attention. Poor active motion stability in anterior/posterior translation may play an important role in the development of knee joint instability, potentially resulting in subsequent ACL deficiency and the development of knee osteoarthritis among people with GJH.

Publisher Correction: Online photochemical derivatization enables comprehensive mass spectrometric analysis of unsaturated phospholipid isomers.

The original version of this Article contained an error in Fig. 2f, in which the phospholipid was incorrectly labelled 'PE' rather than the correct 'PC'. This has now been corrected in the PDF and HTML versions of the Article.

Online photochemical derivatization enables comprehensive mass spectrometric analysis of unsaturated phospholipid isomers.

Mass spectrometry-based lipidomics is the primary tool for the structural analysis of lipids but the effective localization of carbon-carbon double bonds (C=C) in unsaturated lipids to distinguish C=C location isomers remains challenging. Here, we develop a large-scale lipid analysis platform by coupling online C=C derivatization through the Paternò-Büchi reaction with liquid chromatography-tandem mass spectrometry. This provides rich information on lipid C=C location isomers, revealing C=C locations for more than 200 unsaturated glycerophospholipids in bovine liver among which we identify 55 groups of C=C location isomers. By analyzing tissue samples of patients with breast cancer and type 2 diabetes plasma samples, we find that the ratios of C=C isomers are much less affected by interpersonal variations than their individual abundances, suggesting that isomer ratios may be used for the discovery of lipid biomarkers.