Detection of lung cancer through SERS analysis of serum.

Early detection and postoperative assessment are crucial for improving overall survival among lung cancer patients. Here, we report a non-invasive technique that integrates Raman spectroscopy with machine learning for the detection of lung cancer. The study encompassed 88 postoperative lung cancer patients, 73 non-surgical lung cancer patients, and 68 healthy subjects. The primary aim was to explore variations in serum metabolism across these cohorts. Comparative analysis of average Raman spectra was conducted, while principal component analysis was employed for data visualization. Subsequently, the augmented dataset was used to train convolutional neural networks (CNN) and Resnet models, leading to the development of a diagnostic framework. The CNN model exhibited superior performance, as verified by the receiver operating characteristic curve. Notably, postoperative patients demonstrated an increased likelihood of recurrence, emphasizing the crucial need for continuous postoperative monitoring. In summary, the integration of Raman spectroscopy with CNN-based classification shows potential for early detection and postoperative assessment of lung cancer.

KEAP1 promotes anti-tumor immunity by inhibiting PD-L1 expression in NSCLC.

Immunotherapy has become a prominent first-line cancer treatment strategy. In non-small cell lung cancer (NSCLC), the expression of PD-L1 induces an immuno-suppressive effect to protect cancer cells from immune elimination, which designates PD-L1 as an important target for immunotherapy. However, little is known about the regulation mechanism and the function of PD-L1 in lung cancer. In this study, we have discovered that KEAP1 serves as an E3 ligase to promote PD-L1 ubiquitination and degradation. We found that overexpression of KEAP1 suppressed tumor growth and promoted cytotoxic T-cell activation in vivo. These results indicate the important role of KEAP1 in anti-cancer immunity. Moreover, the combination of elevated KEAP1 expression with anti-PD-L1 immunotherapy resulted in a synergistic effect on both tumor growth and cytotoxic T-cell activation. Additionally, we found that the expressions of KEAP1 and PD-L1 were associated with NSCLC prognosis. In summary, our findings shed light on the mechanism of PD-L1 degradation and how NSCLC immune escape through KEAP1-PD-L1 signaling. Our results also suggest that KEAP1 agonist might be a potential clinical drug to boost anti-tumor immunity and improve immunotherapies in NSCLC.

Mediastinal lymph node dissection versus spared mediastinal lymph node dissection in stage IA non-small cell lung cancer presented as ground glass nodules: study protocol of a phase III, randomised, multicentre trial (MELDSIG) in China.

INTRODUCTION: Radical surgery including mediastinal lymph node dissection is the standard treatment for early-stage non-small cell lung cancer (NSCLC). About 50% lung nodules are pure ground glass or part-solid nodules, which are predominantly clinical stage IA NSCLC. Non-solid nodules rarely develop mediastinal lymph node metastasis. METHOD AND ANALYSIS: A phase III study was started in China to evaluate the non-inferiority in overall survival of spared mediastinal lymph node dissection compared with mediastinal lymph node dissection in stage IA NSCLC. A total of 1362 patients will be enrolled from 4 institutions in 2-3 years. The second endpoints are relapse-free survival and perioperative data, including duration of hospitalisation, duration of chest tube placement, operation time, blood loss. ETHICS AND DISSEMINATION: This protocol has been reviewed and approved by the Clinical Research Review Board of Tianjin Medical University Cancer Institute and Hospital. The findings will be disseminated in peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT04631770.

A water pricing model for urban areas based on water accessibility.

Water resource, with properties of scarcity, is one of the vital resource endowments. Like land resources, the prices of these resource endowments should be correlated to their locations to follow fair and reasonable principles. The current water price systems are mainly policy-oriented fixed regimes. And the water use was charged according to the regional-average situation with scarce consideration of the fine-scale geographical water accessibility. With a combination of the water accessibility and the current water pricing regime, this paper first proposed a novel water pricing model, the Water Price at Grid-scale (WPG) model, to dynamically allocate water prices to fine grids for urban residents. The WPG model was examined in the case study of the Han River Basin in the Hubei province of China. The specific results were: (1) the Pgrid of Tier I is between 0.66 and 3.94 yuan/m³, the Pgrid of Tier II is between 0.57 and 5.44 yuan/m³, and the Pgrid of Tier III is between 0.47 and 6.94 yuan/m³ in the study area. (2) the grids with more water acquisition generally have lower water prices than others and vice versa. (3) the average water prices in tiers obtained by the WPG model are generally higher than that derived from the current water pricing system. The results proved that the proposed WPG model spatially allocates the three-tier water prices into grids of urban areas. The WPG framework can be adopted in any society by involving its water price regimes and adjusting the scale of grids and the pricing year. This study provided a new viewpoint of domestic water pricing involving fine-scale water accessibility. The WPG model has great potential to ease water shortage pressure in water-limited societies and can be utilized and loaded into the current smart-city network for efficient and fine-scale water resource management.

Comparison of efficacy and safety of hybrid video-assisted thoracoscopic surgery vs. thoracotomy sleeve lobectomy for non-small cell lung cancer: a propensity score matching study.

Background: It is unclear whether hybrid video-assisted thoracoscopic surgery (VATS) sleeve lobectomy (SL) could be an alternative to thoracotomy SL for non-small cell lung cancer (NSCLC) treatment. The aim of the study is to investigate the safety and efficacy of hybrid VATS SL. Methods: We collected 112 patients who received hybrid VATS SL or thoracotomy SL for primary treatment of NSCLC at Liaoning Cancer Hospital & Institute from November 2016 to September 2021. Perioperative and survival data were collected, and retrospective analysis was conducted on 91 thoracotomy and 21 hybrid VATS SL patients to evaluate the safety and efficacy of two approaches. Propensity score matching (PSM) was used to minimize selection bias. The Kaplan-Meier method was applied to compare overall survival (OS) and recurrence-free survival (RFS). Follow-up data were obtained by outpatient clinical visit and nurse-led telephone. Results: A total of 112 patients were included in this study, including thoracotomy patients (n=91) and hybrid VATS patients (n=21). In the non-match analysis, the baseline data of patients was similar between the two groups, except regarding the receipt of neoadjuvant therapy (P=0.087). After PSM (2:1), a total of 39 thoracotomy patients and 19 hybrid VATS patients were enrolled. The baseline variables were quite similar in both groups. In the hybrid group, the number of lymph nodes (25.9±8.5 vs. 32.9±9.7, P<0.01) and positive lymph nodes (3.7±2.9 vs. 5.6±4.0, P=0.045) were significantly higher than those in the thoracotomy group. The hybrid group was associated with significantly shorter postoperative hospital stay (9.5±3.5 vs. 7.3±2.9, P=0.021) and chest tube duration time (6.6±3.1 vs. 5.3±1.5, P=0.031). No statistical difference in complications, reoperation, and recurrence were observed between the hybrid VATS SL and thoracotomy SL (P=1.0, P=1.0, P=0.472). The 30- and 90-day mortalities showed no differences between approaches (2.6% vs. 0%, P=1.0; 5.1% vs. 5.3%, P=1.0). No significant differences were found between thoracotomy and hybrid VATS SL in 3-year OS (P=0.614) and 3-year RFS (P=0.750). Conclusions: Hybrid VATS SL lobectomy may be a safe and feasible approach associated with similar oncologic prognosis and better postoperative recovery compared with thoracotomy SL for NSCLC treatment.

Quantification of 3-bromopyruvate in rat plasma by HPLC-MS/MS employing precolumn derivatization and the application to a pharmacokinetics study.

A simple high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method has been developed for the determination of 3-bromopyruvate (3-BrPA) in rat plasma for the first time. The analytes were separated on a C18 column (100 × 2.1 mm, 1.7 µm) and a triple-quadrupole mass spectrometry equipped with an electrospray ionization source was applied for detection. 3-BrPA was extracted from rat plasma with protein precipitation, and then derivatized with 4-nitro-1,2-phenylenediamine to obtain the mass signal because 3-BrPA could not be detected in mass spectrometry. The method was fully validated according to the US Food and Drug Administration guidance. The method was linear over the concentration range 0.5-1,000.0 ng/ml for 3-BrPA. The precision and accuracy, extraction recovery, and matrix effect were within acceptable limits. The method was then applied to support a pharmacokinetic study after 3-BrPA and 3-BrPA-l-Val-l-Ile (a dipeptide prodrug of 3-BrPA, 3-BrPA-l-Valine-l-isoleucine) had been administered to the Sprague-Dawley rats, respectively.

The Correlation between Functional Connectivity of the Primary Somatosensory Cortex and Cervical Spinal Cord Microstructural Injury in Patients with Cervical Spondylotic Myelopathy.

OBJECTIVES: To explore functional connectivity reorganization of the primary somatosensory cortex, the chronic microstructure damage of the cervical spinal cord, and their relationship in cervical spondylotic myelopathy (CSM) patients. METHODS: Thirty-three patients with CSM and 23 healthy controls (HCs) were recruited for rs-fMRI and cervical spinal cord diffusion tensor imaging (DTI) scans. Six subregions (including leg, back, chest, hand, finger and face) of bilateral primary somatosensory cortex (S1) were selected for seed-based whole-brain functional connectivity (FC). Then, we calculated the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values of the cervical spinal cord. Correlation analysis was conducted between FC values of brain regions and DTI parameters of cervical spinal cord (ADC, FA), and their relationship with each other and clinical parameters. RESULTS: Compared with the HC group, the CSM group showed decreased FC between areas of the left S1hand, the left S1leg, the right S1chest, and the right S1leg with brain regions. The mean FA values of the cervical spinal cord in CSM patients were positively correlated with JOA scores. Especially, the FApos values of bilateral posterior funiculus were positively correlated with JOA scores. The ADC and FA values of bilateral posterior funiculus in the cervical spinal cord were also positively correlated with the FC values. CONCLUSIONS: There was synchronization between chronic cervical spinal cord microstructural injury and cerebral cortex sensory function compensatory recombination. DTI parameters of the posterior cervical spinal cord could objectively reflect the degree of cerebral cortex sensory function impairment to a certain extent.

An aberrant anterior ascending segmental pulmonary artery (A3aii) in a patient with lung cancer.

A 60-year-old woman was admitted to our department for a left upper lobe and left lower lobe ground glass nodules. Three-dimensional computed tomography bronchography and angiography showed an aberrant anterior ascending segmental pulmonary artery (A3aii) branching from the lingular artery. We performed left upper division segmentectomy and left lower superior segmentectomy for ground glass opacity lesions, and the A3aii variation artery was safely dissected. The patient received an uneventful recovery, and the final pathologic diagnosis was early-stage multiple primary lung cancers. The A3aii branching of the lingular artery was extremely rare. Preoperative three-dimensional computed tomography bronchography and angiography was important to provide accurate vessel variation information and achieve accurate and safe segmentectomy procedure.

Label-free surface-enhanced Raman spectroscopy for diagnosis and analysis of serum samples with different types lung cancer.

Screening and detection of early lung cancer is important for diagnosis and prognosis. Intervention in early stage of lung cancer can significantly improve the cure and survival of patients. Surface-enhanced Raman spectroscopy (SERS) is an increasingly popular method of diagnosing cancer. We used silver nanoparticles (AgNPs) as the Raman-enhanced substrate to increase Raman signals, which contributes to the subsequent classification of lung cancer and normal serum. SERS acquired from the serum indicated the difference in biochemical components between cancerous (n = 51) lung serum and normal (n = 18) serum. Principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) were utilized to establish the identification model, and the various indicators of PLS-DA were all superior to those of the PLS model. Our study offers a new proposal for the universal applicability of analysis and identification with SERS of serum samples in clinical diagnosis.

Steganography and Steganalysis in Voice over IP: A Review.

The rapid advance and popularization of VoIP (Voice over IP) has also brought security issues. VoIP-based secure voice communication has two sides: first, for legitimate users, the secret voice can be embedded in the carrier and transmitted safely in the channel to prevent privacy leakage and ensure data security; second, for illegal users, the use of VoIP Voice communication hides and transmits illegal information, leading to security incidents. Therefore, in recent years, steganography and steganography analysis based on VoIP have gradually become research hotspots in the field of information security. Steganography and steganalysis based on VoIP can be divided into two categories, depending on where the secret information is embedded: steganography and steganalysis based on voice payload or protocol. The former mainly regards voice payload as the carrier, and steganography or steganalysis is performed with respect to the payload. It can be subdivided into steganography and steganalysis based on FBC (fixed codebook), LPC (linear prediction coefficient), and ACB (adaptive codebook). The latter uses various protocols as the carrier and performs steganography or steganalysis with respect to some fields of the protocol header and the timing of the voice packet. It can be divided into steganography and steganalysis based on the network layer, the transport layer, and the application layer. Recent research results of steganography and steganalysis based on protocol and voice payload are classified in this paper, and the paper also summarizes their characteristics, advantages, and disadvantages. The development direction of future research is analyzed. Therefore, this research can provide good help and guidance for researchers in related fields.

Cortical anatomy plasticity in cases of cervical spondylotic myelopathy associated with decompression surgery: A strobe-compliant study of structural magnetic resonance imaging.

ABSTRACT: Using voxel-based morphometry (VBM), we studied cortical gray matter volume changes in patients with cervical spondylotic myelopathy (CSM) before and after cervical cord surgical decompression. We then discussed the structural damage mechanisms and the neural plasticity mechanisms involved in postsurgical CSM.Forty-five presurgical CSM patients, 41 of the same group followed-up 6 months after decompression surgery and 45 normal controls (NC) matched for age, sex and level of education underwent high-resolution 3-dimensional T1-weighted scans by 3.0 T MR. Then, VBM measurements were compared and cortical gray matter volume alterations were assessed among pre- or postsurgical CSM patients and NC, as well as correlations with clinical indexes by Pearson correlation.Compared with NC, presurgical CSM patients showed reduced gray matter volume in the left caudate nucleus and the right thalamus. After 6 months, postsurgical CSM patients had lower gray matter volume in the bilateral cerebellar posterior lobes but had higher gray matter volume in the brain-stem than did presurgical CSM patients. Postsurgical CSM patients had significantly lower gray matter volume in the left caudate nucleus but greater regional gray matter volume in the right inferior temporal gyrus, the right middle orbitofrontal cortex (OFC) and the bilateral lingual gyrus / precuneus /posterior cingulate cortex than did NC. Abnormal areas gray volume in presurgical CSM and postsurgical CSM patients showed no significant correlation with clinical data (P > .05).Myelopathy in the cervical cord may cause chronic cerebral structural damage before and after the decompression stage, markedly in outlier brain regions involving motor execution/control, vision processing and the default mode network and in areas associated with brain compensatory plasticity to reverse downstream spinal cord compression and respond to spinal cord surgical decompression.

Pectus excavatum requiring temporary pacemaker implantation before Nuss procedure: a case report.

Pectus excavatum is the most common chest wall deformity, and some patients also have it combined with cardiac arrhythmias. It is a rare occurrence for there to be a severe conduction block that requires a temporary pacemaker implantation before the surgical correction. Here we reported a case of pectus excavatum with a second-degree atrial-ventricular (AV) block (Mobitz II) who had temporary pacemaker implantation before the Nuss procedure. The young patient had a chest wall deformity for 6 years and it got worse with age. The Haller index was 4.21, and we evaluated that he should receive the Nuss procedure. An AV block was found during the preoperative electrocardiogram examination; furthermore, Holter monitor proved that he had first-degree AV block and a second-degree AV block (Mobitz II). After consultation with the anesthesiologist and cardiologist, we suggested that a temporary pacemaker placement should be performed under local anesthesia before the minimally invasive operation and removed as soon as the patient revived from general anesthesia. A postoperative Holter monitor was implemented, and the conduction defect disappeared shortly after the operation. However, the Holter monitor showed that the conduction defect was still existed during the follow-up period, which indicated that severe conduction defects should be originated from the conduction system itself, rather than the compression to the heart. The temporary pacemaker was essential to ensure the conducting of the operation went smoothly.

Checkpoint therapeutic target database (CKTTD): the first comprehensive database for checkpoint targets and their modulators in cancer immunotherapy.

BACKGROUND: Checkpoint targets play a key role in tumor-mediated immune escape and therefore are critical for cancer immunotherapy. Unfortunately, there is a lack of bioinformatics resource that compile all the checkpoint targets for translational research and drug discovery in immuno-oncology. METHODS: To this end, we developed checkpoint therapeutic target database (CKTTD), the first comprehensive database for immune checkpoint targets (proteins, miRNAs and LncRNAs) and their modulators. A scoring system was adopted to filter more relevant targets with high confidence. In addition, a few biological databases such as Oncomine, Drugbank, miRBase and Lnc2Cancer database were integrated into CKTTD to provide an in-depth information. Moreover, we computed and provided ligand-binding site information for all the targets which may support bench scientists for drug discovery efforts. RESULTS: In total, CKTTD compiles 105 checkpoint protein targets, 53 modulators (small-molecules and antibody), 30 miRNAs and 18 LncRNAs in cancer immunotherapy with validated experimental evidences curated from 10 649 literatures via an enhanced text-mining system. CONCLUSIONS: In conclusion, the CKTTD may serve as a useful platform for the research of cancer immunotherapy and drug discovery. The CKTTD database is freely available to public at http://www.ckttdb.org/.

Clinical application of enhanced recovery after surgery (ERAS) in pectus excavatum patients following Nuss procedure.

BACKGROUND: Evaluate the effect of enhanced recovery after surgery (ERAS) protocol on postoperative recovery quality of pectus excavatum patients with Nuss procedure. METHODS: A retrospective study was performed on patients undergoing Nuss procedure from the Department of Thoracic Surgery of The Cancer Hospital of China Medical University between September 2016 and September 2019. Patients were divided into 2 groups by perioperative management: the traditional procedure group (T group) and the ERAS strategy group (E group). The outcome measures were postoperative drainage time, postoperative hospital time, and postoperative complications measured by the Clavien-Dindo method. RESULTS: Of the 168 patients from this time period, 148 met the inclusion criteria (75 in Group T and 73 in Group E). All operations involved in this study were completed successfully. There was no statistical difference between the 2 groups with respect to baseline demographics (P>0.05). In Group E, postoperative drainage time (2.53±0.72 vs. 3.45±2.07 days) and postoperative hospitalization time (4.96±1.48 vs. 7.71±7.78 days) were statistically significantly better than those in Group T (P<0.05). There was no difference in overall postoperative complications as measured by Clavien-Dindo score. CONCLUSIONS: The measures of no indwelling urinary catheter (IDUC), laryngeal mask anesthesia, and indwelling tubule drainage can improve postoperative recovery quality of pectus excavatum patients following Nuss procedure.

LncRNA SBF2-AS1 affects the radiosensitivity of non-small cell lung cancer via modulating microRNA-302a/MBNL3 axis.

Background: Long non-coding RNAs (lncRNAs) have been reported to participate in many diseases including non-small cell lung cancer (NSCLC), thus our objective was to investigate the impact of lncRNA SBF2-AS1 modulating microRNA-302a (miR-302a) expression on radiosensitivity of NSCLC.Methods: The expression of SBF2-AS1, miR-302a and muscleblind-like 3 (MBNL3) in NSCLC tissues of the radiotherapy-sensitive and radiotherapy-resistant groups was tested. The radiosensitivity of parent and resistant strains (NCI-H1299 and NCI-H1299R cells) was detected. Further, cells were treated with si-SBF2-AS1 and miR-302a mimics to determine their roles in proliferation and apoptosis of parent strain and resistant strain cells as well as transfected cells. The in-vivo growth capacity of the cells and the effect of radiotherapy on tumor size of NSCLC were detected.Results: Up-regulated SBF2-AS1 and MBNL3 and down-regulated miR-302a in NSCLC tissues of the radiotherapy resistant group. Overexpression of SBF2-AS1 and MBNL3 and low expression of miR-302a were witnessed in NCI-H1299R cells. Down-regulated SBF2-AS1 or up-regulated miR-302a suppressed the proliferation while boosted the apoptosis of NCI-H1299 cells and decreased the radioresistance of the NCI-H1299R cells. Silencing SBF2-AS1 or up-regulating miR-302a restrained tumor growth in vivo.Conclusion: Our study presents that high expression of miR-302a or inhibition of SBF2-AS1 can enhance the radiosensitivity and apoptosis of NSCLC cells through downregulation of MBNL3, which is a therapeutic target for NSCLC.

Feasibility of nodal classification for non-small cell lung cancer by merging current N categories with the number of involved lymph node stations.

INTRODUCTION: The aim of this study was to assess the prognoses of patients with non-small cell lung cancer (NSCLC) according to the current nodal (N) categories of the tumor, node and metastasis (TNM) classification and the number of involved lymph node stations. METHODS: Five hundred and seventy patients with NSCLC underwent surgery from 1 January 2005 to 31 December 2009 and were analysed retrospectively. Postoperative overall survival was analysed according to two nodal classifications: the current N0, N1, N2 and N3 categories and those based on the number of involved nodal stations: N0, N1a (single N1), N1b (multiple N1), N2a1 (single N2 without N1), N2a2 (single N2 with N1), N2b1 (multiple N2 without N1) and N2b2 (multiple N2 with N1). RESULTS: Five-year survival rates were 76.1%, 53.4% and 26.3% for N0, N1 and N2, respectively (P < 0.001). When survival was analysed by the number of involved nodal stations, the groups with significant differences were maintained; otherwise, they were merged, and new codes were assigned as follows for exploratory analyses: NA (N0), NB (N1a), NC (N1b, N2a (i.e., N2a1 and N2a2) and N2b1) and ND (N2b2). Five-year survival rates were 76.1%, 60.0%, 39.1%, and 11.4% for NA, NB, NC and ND, respectively, and there were significant differences among them. This N classification was an independent prognostic factor in multivariate analyses. CONCLUSION: Pending prospective and international validation, it is practical to merge the current N categories with the number of involved lymph node stations when evaluating the postoperative prognosis of NSCLC patients.

[Progress of Experimental Researches on Mechanisms of Acupuncture Underlying Improvement of Ischemic Cerebral Vascular Disease by Regulating Different Intracellular Signaling Pathways].

China is in the "high death zone" of the world cerebrovascular disease (CVD) map. The prevention and treatment of ischemic CVD (ICVD) have become the top priority in clinical practice. It has been demonstrated that acupuncture therapy has a positive role in bettering clinical symptoms of ICVD patients. Findings of recent experimental studies displayed that electroacupuncture (EA) intervention is effective in reducing the cerebral infarcted volume and cellular injury, promoting proliferation, migration and differentiation of nerve stem cells, facilitating the regeneration of nerve tissue, bettering dysneuria and limb locomotor ability, etc. in ICVD rats, which are closely associated with its effects in regulating different intracellular signaling pathways. In the present study, we review the progress of recent experimental studies on the underlying mechanisms of EA in improving ICVD from six major signaling pathways including Notch, mitogen-activated protein kinases (MAPK)/ extracellular signal regulated protein kinases (ERK), phosphatidy linositol-3-kinase (PI 3 K)/ protein kinase B (Akt), Janus kinase-signal transducer and activator of transcription (JAK-STAT), erythropoietin-producing hepatocyte receptor (Eph)/Ephrin, nuclear factor of kappa B (NF-κB) and their compositions, which may provide new therapeutic targets for acupuncture treatment of ICVD. More attention should be paid to the comparison of the efficacy of acupuncture of different acupoint combinations (traditional acupoint formulas) in relieving ICVD.

The feasibility and safety of thoracoscopic surgery under epidural and/or local anesthesia for spontaneous pneumothorax: a meta-analysis.

The aim of this study was to compare thoracoscopic surgery for spontaneous pneumothorax under epidural and/or local anesthesia (ELA) with that under general anesthesia and prove the feasibility and safety of thoracoscopic surgery under ELA for spontaneous pneumothorax. Relevant studies were searched in five databases from their date of publication to June 2016. We collected and analyzed the data concerning operative time, hospital stay, complications, air leak, recurrence and perioperative mortality. A forest plot was performed to compare the differences between the two groups. There were no significant differences between the ELA group and the general anesthesia (GA) group in operative time, hospital stay, complications, air leak or recurrence. There were 6 deaths reported in two studies. However, patients in the ELA group had significantly shorter global operating room time. Our study demonstrated that ELA, in comparison with GA, is feasible and safe for thoracoscopic surgery of spontaneous pneumothorax.