Background: Lung cancer is the leading cause of cancer-related deaths. Survival rate improves significantly with early detection of lung cancer. Effective methods of early detection can reduce lung cancer mortality to a large extent as well as benefit the whole public health. The diagnostic value of one single marker is relatively low. Combined autoantibodies (AABs) can improve the sensitivity significantly rather than rely on one AAB and serve as good reservoir for early detection of lung cancer. Patients and methods: We designed three parts in our experiment. In training set we measured the expression levels of AABs in 100 non-small-cell lung cancer (NSCLC) patients and 60 healthy controls by using ELISA detection method. A blinded validation was subsequently performed in 254 NSCLC patients, 125 healthy controls, and 71 nodule patients. A prospective expansion set was performed to evaluate the diagnosis value of AABs combined detection. Results: Both in training set and validation set, the concentrations of SOX2, GAGE 7, MAGE A1, and P53 in NSCLC group increased prominently when compared to the healthy group (P<0.05). The concentration of GBU4-5 in adenocarcinoma group was higher than in the squamous cell carcinoma (SCC) group (P<0.05); the PGP9.5, which was opposite, in SCC group was higher than in the adenocarcinoma group (P<0.05). The positive rate of each AAB did not show any bias with age, gender, smoking history, and tumor location. Most importantly, different choice of biomarkers led to different detection results. Conclusion: Our study confirmed the diagnostic value of tumor-associated AABs. They may be useful as latent tumor markers to facilitate the detection of early lung cancer.

We described the prevalence of clofazimine (CFZ) resistance in a multidrug-resistant tuberculosis (MDR-TB) cohort in China. We also aimed to identify dynamic changes in CFZ susceptibility and its molecular mechanism after exposure to bedaquiline (BDQ) and/or CFZ. The experimental settings were conducted based on our MDR-TB cohort receiving BDQ-containing regimens. Sequential isolates were obtained from patients. CFZ and BDQ susceptibility of isolates were determined using the minimum inhibitory concentration (MIC) method. The fragments of Rv0678 and pepQ were sequenced. A total of 277 patients infected with MDR-TB were included in our study. CFZ resistance was noted in 23 (23/277, 8.3%) isolates. The rate of acquired CFZ resistance (12/189, 6.3%) was significantly greater than that of primary resistance (11/88, 12.5%, P = 0.028). Out of 23 CFZ-resistant isolates, five (5/23) were BDQ-resistant, and the other 18 (18/23) were susceptible to BDQ. Of note, nine 9/23) out of 23 CFZ-resistant isolates had mutations within either target genes. Kaplan-Meier analysis demonstrated that the baseline CFZ resistance had no influence on time to culture conversion in our cohort (P = 0.828). Acquired CFZ resistance emerged in eight (8/94, 8.5%) patients during treatment for MDR-TB, including three patients receiving regimens without CFZ. Our results demonstrate the high rate of CFZ resistance among MDR-TB patients in China. Patients treated with BDQ-containing regimens achieve comparative culture conversion rate regardless of baseline CFZ susceptibility. The presence of acquired CFZ-resistance following BDQ treatment without known mutation indicates that other mechanisms conferring cross resistance to these two compounds may exist.

Although Cisplatin (DDP) is a widely used first-line chemotherapy medication, DDP resistance is one of the main causes of treatment failure in advanced lung cancer. Therefore, it is urgent to identify DDP sensitizers and investigate the underlying molecular mechanisms. Here we utilized DDP-resistant organoids established from tumor biopsies of patients with relapsed lung cancers. In this study, we identified Solamargine as a potential DDP sensitizer through screening a natural product library. Mechanically, Solamargine induced G0/G1-phase arrest and apoptosis in DDP-resistant lung cancer cell lines. Gene expression analysis and KEGG pathway analysis indicated that the hedgehog pathway was suppressed by Solamargine. Moreover, Gli responsive element (GRE) reporter gene assay and BODIPY-cyclopamine binding assay showed that Solamargine inhibited the hedgehog pathway via direct binding to SMO protein. Interestingly, Solamargine and DDP showed a synergetic effect in inhibiting DDP-resistant lung cancer cell lines. Taken together, our work herein revealed Solamargine as a hedgehog pathway inhibitor and DDP-sensitizer, which might provide a new direction for further treatment of advanced DDP-resistant lung cancer patients.

Objective: To evaluate the consistency between doctors and artificial intelligence (AI) software in analysing and diagnosing pulmonary nodules, and assess whether the characteristics of pulmonary nodules derived from the two methods are consistent for the interpretation of carcinomatous nodules. Materials and Methods: This retrospective study analysed participants aged 40–74 in the local area from 2011 to 2013. Pulmonary nodules were examined radiologically using a low-dose chest CT scan, evaluated by an expert panel of doctors in radiology, oncology, and thoracic departments, as well as a computer-aided diagnostic(CAD) system based on the three-dimensional(3D) convolutional neural network (CNN) with DenseNet architecture(InferRead CT Lung, IRCL). Consistency tests were employed to assess the uniformity of the radiological characteristics of the pulmonary nodules. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic accuracy. Logistic regression analysis is utilized to determine whether the two methods yield the same predictive factors for cancerous nodules. Results: A total of 570 subjects were included in this retrospective study. The AI software demonstrated high consistency with the panel's evaluation in determining the position and diameter of the pulmonary nodules (kappa = 0.883, concordance correlation coefficient (CCC) = 0.809, p = 0.000). The comparison of the solid nodules' attenuation characteristics also showed acceptable consistency (kappa = 0.503). In patients diagnosed with lung cancer, the area under the curve (AUC) for the panel and AI were 0.873 (95%CI: 0.829–0.909) and 0.921 (95%CI: 0.884–0.949), respectively. However, there was no significant difference (p = 0.0950). The maximum diameter, solid nodules, subsolid nodules were the crucial factors for interpreting carcinomatous nodules in the analysis of expert panel and IRCL pulmonary nodule characteristics. Conclusion: AI software can assist doctors in diagnosing nodules and is consistent with doctors' evaluations and diagnosis of pulmonary nodules.

Objectives To compare the effects of programmed intermittent bolus infusion (PIBI), continuous thoracic paravertebral infusion (CTPI), and continuous intravenous infusion (CII) on postoperative analgesia in patients undergoing video-assisted thoracoscopic surgery (VATS). Design Prospective, randomized, controlled. Setting The operating room, post-anesthesia care unit, and patient ward of a university hospital. Participants Ninety patients with American Society of Anesthesiologists (ASA) physical status Ι to II, aged 35-70 years, and scheduled for VATS. Interventions Postoperative analgesia was randomized to PIBI, CTPI, and CII. Measurements and Main Results The primary outcome was the numeric rating scale (NRS) score at rest and during coughing at 1, 4, 24, and 48 hours after surgery. The secondary outcomes included the actual and effective numbers of patient-controlled analgesia (PCA), ropivacaine use, Ramsay sedation scale score, quality of recovery-15 (QoR-15) score, values of hemodynamic parameters at different periods, intraoperative consumption of anesthetic drugs, and postoperative adverse events. Postoperatively, the NRS score was reduced in the PIBI group compared with the CTPI and CII groups at rest and during coughing (p < 0.05). The number of PCAs was significantly lower in the PIBI group compared with the CTPI and CII groups (p < 0.05). The QoR-15 score noticeably increased in the PIBI group compared with the CTPI and CII groups (p = 0.001 and p = 0.000, respectively). Conclusions PIBI outperformed CTPI and CII in inducing analgesia for postoperative pain in patients undergoing VATS.