STING directly recruits WIPI2 for autophagosome formation during STING-induced autophagy.

The cGAS-STING pathway plays an important role in host defense by sensing pathogen DNA, inducing type I IFNs, and initiating autophagy. However, the molecular mechanism of autophagosome formation in cGAS-STING pathway-induced autophagy is still unclear. Here, we report that STING directly interacts with WIPI2, which is the key protein for LC3 lipidation in autophagy. Binding to WIPI2 is necessary for STING-induced autophagosome formation but does not affect STING activation and intracellular trafficking. In addition, the specific interaction between STING and the PI3P-binding motif of WIPI2 leads to the competition of WIPI2 binding between STING and PI3P, and mutual inhibition between STING-induced autophagy and canonical PI3P-dependent autophagy. Furthermore, we show that the STING-WIPI2 interaction is required for the clearance of cytoplasmic DNA and the attenuation of cGAS-STING signaling. Thus, the direct interaction between STING and WIPI2 enables STING to bypass the canonical upstream machinery to induce LC3 lipidation and autophagosome formation.

High-precision Helicobacter pylori infection diagnosis using a dual-element multimodal gas sensor array.

Helicobacter pylori (H. pylori) is a globally widespread bacterial infection. Early diagnosis of this infection is vital for public and individual health. Prevalent diagnosis methods like the isotope 13C or 14C labelled urea breath test (UBT) are not convenient and may do harm to the human body. The use of cross-response gas sensor arrays (GSAs) is an alternative way for label-free detection of metabolite changes in exhaled breath (EB). However, conventional GSAs are complex to prepare, lack reliability, and fail to discriminate subtle changes in EB due to the use of numerous sensing elements and single dimensional signal. This work presents a dual-element multimodal GSA empowered with multimodal sensing signals including conductance (G), capacitance (C), and dissipation factor (DF) to improve the ability for gas recognition and H. pylori-infection diagnosis. Sensitized by poly(diallyldimethylammonium chloride) (PDDA) and the metal-organic framework material NH2-UiO66, the dual-element graphene oxide (GO)-composite GSAs exhibited a high specific surface area and abundant adsorption sites, resulting in high sensitivity, repeatability, and fast response/recovery speed in all three signals. The multimodal sensing signals with rich sensing features allowed the GSA to detect various physicochemical properties of gas analytes, such as charge transfer and polarization ability, enhancing the sensing capabilities for gas discrimination. The dual-element GSA could differentiate different typical standard gases and non-dehumidified EB samples, demonstrating the advantages in EB analysis. In a case-control clinical study on 52 clinical EB samples, the diagnosis model based on the multimodal GSA achieved an accuracy of 94.1%, a sensitivity of 100%, and a specificity of 90.9% for diagnosing H. pylori infection, offering a promising strategy for developing an accurate, non-invasive and label-free method for disease diagnosis.

The efficacy and feasibility of neoadjuvant immunotherapy plus chemotherapy followed by McKeown minimally invasive oesophagectomy for locally advanced oesophageal squamous cell carcinoma.

Introduction: In immunotherapy, antibodies are activated to block immune checkpoints, resist tumour immunosuppression, shrink tumours and prevent a recurrence. As the science behind tumour immunotherapy continuously develops and improves, neoadjuvant immunotherapy bears more prominent advantages: antigen exposure not only enhances the degree of tumour-specific T-cell response but also prolongs the duration of actions. In this study, we evaluated the efficacy and safety of McKeown minimally invasive oesophagectomy (McKeown MIO) following neoadjuvant immunotherapy combined with chemotherapy (NICT) in patients with locally advanced oesophageal cancer (OC). Patients and Methods: In this retrospective study, 94 patients underwent either NICT or neoadjuvant chemotherapy (NCT) followed by MIO at our institution from January 2020 to October 2022. We assessed the therapy-related adverse events and perioperative outcomes and compared them between the two groups. Results: After completing at least two cycles of neoadjuvant therapy, all patients underwent McKeown MIO with negative margins within 4-7 weeks. Demographic data of the two cohorts were similar. Regarding perioperative characteristics, the median intraoperative blood loss was 50 ml in the NICT group, lower than that of the NCT group (100 ml, P < 0.05). In addition, the NICT group had significantly more harvested lymph nodes than the NCT group (P < 0.05). No significant differences were found in post-operative complications. The rate of objective response rate in the NICT group was higher than that in the NCT group (88.3% vs. 58.8%). Regarding tumour regression, the number of patients with TRG Grades 1-3 in the NICT group was more than that in the NCT. Adverse events experienced by the two groups included anaemia and elevated transaminase. We found no difference in the adverse events between the two groups. Conclusions: This study showed the efficacy and feasibility of NICT followed by McKeown MIO in treating locally advanced OC.

[Endoscopic trans-fistula drainage for gastroesophageal anastomotic fistula with para-fistula abscess after esophagectomy].

Objective: To evaluate the efficiency and safety of endoscopic trans-fistula drainage (ETFD) for gastroesophageal anastomotic fistula with para-fistula abscess after esophagectomy. Methods: Among 456 esophageal cancer patients receiving esophagectomy between February 2012 and February 2017 in Sir Run Run Shaw Hospital, 15 cases were diagnosed as gastroesophageal anastomotic fistula with para-fistula abscess after surgery. Seven cases received ETFD treatment (ETFD group), and 8 cases received conventional treatment (control group). Recovery of inflammatory markers and fistula, length of hospital stay after esophagectomy and total medical expenses were compared between ETFD group and control group. Results: All patients recovered in ETFD group. Time of white cell count returning to normal and decline of C-reactive protein, time of fistula healing and length of hospital stay after esophagectomy in ETFD group were significantly shorter than those of control group (all P<0.05). And medical expenses in ETFD group was also lower (P<0.05). Conclusion: ETFD is effective and safe for gastroesophageal anastomotic fistula with para-fistula abscess after esophagectomy.

Identification of subgroups and development of prognostic risk models along the glycolysis-cholesterol synthesis axis in lung adenocarcinoma.

Lung cancer is one of the most dangerous malignant tumors affecting human health. Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer. Both glycolytic and cholesterogenic pathways play critical roles in metabolic adaptation to cancer. A dataset of 585 LUAD samples was downloaded from The Cancer Genome Atlas database. We obtained co-expressed glycolysis and cholesterogenesis genes by selecting and clustering genes from Molecular Signatures Database v7.5. We compared the prognosis of different subtypes and identified differentially expressed genes between subtypes. Predictive outcome events were modeled using machine learning, and the top 9 most important prognostic genes were selected by Shapley additive explanation analysis. A risk score model was built based on multivariate Cox analysis. LUAD patients were categorized into four metabolic subgroups: cholesterogenic, glycolytic, quiescent, and mixed. The worst prognosis was the mixed subtype. The prognostic model had great predictive performance in the test set. Patients with LUAD were effectively typed by glycolytic and cholesterogenic genes and were identified as having the worst prognosis in the glycolytic and cholesterogenic enriched gene groups. The prognostic model can provide an essential basis for clinicians to predict clinical outcomes for patients. The model was robust on the training and test datasets and had a great predictive performance.

Feasibility of twenty-four-hour discharge of patients with anterior mediastinal tumors after subxiphoid video-assisted thoracoscopic surgery (VATS) procedure.

Background: A wide variety of surgical procedures are administrated in day-surgery unit and are able to be discharged within 24 hours with high efficiency, safety and economy. This study sought to evaluate the safety and feasibility of 24-hour discharge of patients with anterior mediastinal tumors after subxiphoid video-assisted thoracoscopic surgery (VATS) and describe our surgery procedure experiences. Methods: A total of 70 selected patients with anterior mediastinal tumors undergoing subxiphoid VATS were included in this prospective study. The patients' clinical features, intraoperative and postoperative complications were assessed, and postoperative pain scale and satisfaction scores were also evaluated. Results: The subxiphoid VATS was completed with no conversion to open surgery in all included patients and were all discharged within 24 hours after surgery. The mean operative time ± standard deviation (SD) was 70.50±18.98 min, and the mean operative blood loss volume ± SD was 45.50±15.25 mL. In addition, 80% of the patients reported a postoperative pain scale score less than 3 by the day before discharge, and all patients expressed satisfaction with receiving VATS in the day-surgery unit at 2 weeks after discharge. Conclusions: The use of subxiphoid VATS is a safe, efficient and feasible surgical approach for patients with anterior mediastinal tumors discharged within 24 hours.

Integrating network pharmacology and computational biology to propose Yiqi Sanjie formula's mechanisms in treating NSCLC: molecular docking, ADMET, and molecular dynamics simulation.

Background: Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related deaths globally. Current treatments often do not fully meet efficacy and quality of life expectations. Traditional Chinese medicine (TCM), particularly the Yiqi Sanjie formula, shows promise but lacks clear mechanistic understanding. This study addresses this gap by investigating the therapeutic effects and underlying mechanisms of Yiqi Sanjie formula in NSCLC. Methods: We utilized network pharmacology to identify potential NSCLC drug targets of the Yiqi Sanjie formula via the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Compounds with favorable oral bioavailability and drug-likeness scores were selected. Molecular docking was conducted using AutoDock Vina with structural data from the Protein Data Bank and PubChem. Molecular dynamics (MD) simulations were performed with Desmond Molecular Dynamics System, analyzing interactions up to 500 nanoseconds using the OPLS4 force field. ADMET predictions were executed using SwissADME and ADMETlab 2.0, assessing pharmacokinetic properties. Results: Using network pharmacology tools, we performed Search Tool for the Retrieval of Interaction Genes/Proteins (STRING) analysis for protein-protein interaction, Kyoto Encyclopedia of Genes and Genomes (KEGG) for pathway enrichment, and gene ontology (GO) for functional enrichment, identifying crucial signaling pathways and biological processes influenced by the hit compounds bifendate, xambioona, and hederagenin. STRING analysis indicated substantial connectivity among the targets, suggesting significant interactions within the cell cycle regulation and growth factor signaling pathways as outlined in our KEGG results. The GO analysis highlighted their involvement in critical biological processes such as cell cycle control, apoptosis, and drug response. Molecular docking simulations quantified the binding efficiencies of the identified compounds with their targets-CCND1, CDK4, and EGFR-selected based on high docking scores that suggest strong potential interactions crucial for NSCLC inhibition. Subsequent MD simulations validated the stability of these complexes, supporting their potential as therapeutic interventions. Additionally, the novel identification of ADH1B as a target underscores its prospective significance in NSCLC therapy, further expanded by our comprehensive bioinformatics approach. Conclusions: Our research demonstrates the potential of integrating network pharmacology and computational biology to elucidate the mechanisms of the Yiqi Sanjie formula in NSCLC treatment. The identified compounds could lead to novel targeted therapies, especially for patients with overexpressed targets. The discovery of ADH1B as a therapeutic target adds a new dimension to NSCLC treatment strategies. Further studies, both in vitro and in vivo, are needed to confirm these computational findings and advance these compounds towards clinical trials.

A Prototype of Graphene E-Nose for Exhaled Breath Detection and Label-Free Diagnosis of Helicobacter Pylori Infection.

Helicobacter pylori (HP), a common microanaerobic bacteria that lives in the human mouth and stomach, is reported to infect ≈50% of the global population. The current diagnostic methods for HP are either invasive, time-consuming, or harmful. Therefore, a noninvasive and label-free HP diagnostic method needs to be developed urgently. Herein, reduced graphene oxide (rGO) is composited with different metal-based materials to construct a graphene-based electronic nose (e-nose), which exhibits excellent sensitivity and cross-reactive response to several gases in exhaled breath (EB). Principal component analysis (PCA) shows that four typical types of gases in EB can be well discriminated. Additionally, the potential of the e-nose in label-free detection of HP infection is demonstrated through the measurement and analysis of EB samples. Furthermore, a prototype of an e-nose device is designed and constructed for automatic EB detection and HP diagnosis. The accuracy of the prototype machine integrated with the graphene-based e-nose can reach 92% and 91% in the training and validation sets, respectively. These results demonstrate that the highly sensitive graphene-based e-nose has great potential for the label-free diagnosis of HP and may become a novel tool for non-invasive disease screening and diagnosis.

Age at first sexual intercourse, age at menarche, and age at menopause: a mendelian randomization study on lung cancer risk.

Background: There is increasing evidence that sex hormones are involved in the development of lung cancer, but the correlation between the reproductive behavior that changes sex hormone levels and lung cancer is not yet clear. Many previous studies have investigated the association between reproductive factors and lung cancer risk, but the results have been inconsistent. Therefore, we conducted a two-sample Mendelian randomization (MR) analysis to explore the potential relationship between age at first sexual intercourse (AFS), age at menarche, and age at menopause, and lung cancer. Methods: We performed a MR analysis of the data from the genome-wide association study (GWAS) of European ancestry to evaluate the independent effects of three reproductive behaviors on lung cancer overall (LUCA), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), and small cell lung cancer (SCLC). We mainly used the inverse-variance weighting method for the MR analysis. Sensitivity was determined by a MR-pleiotropy residual sum and outlier analysis, a weighted median analysis, a MR-Egger analysis, and a leave-one-out analysis. Results: The MR analysis results revealed that older AFS had a causal relationship with LUCA [odds ratio (OR) =0.6283, 95% confidence interval (CI): 0.4959-0.7961, P=0.0001), LUAD (OR =0.7042, 95% CI: 0.4967-0.9984, P=0.049), and LUSC (OR =0.6231, 95% CI: 0.4386-0.8853, P=0.0083). Conclusions: Our results revealed a causal relationship between older AFS and a lower risk of lung cancer. Our findings emphasize the importance of providing sex education, as early sexual intercourse may have undesirable effects. In addition, early psychological treatment is also essential.

Analysis of related factors and treatment effect of chylothorax after lung surgery.

Background: Chylothorax is a seldom encountered complication following lung surgery. However, due to the widespread practice of lung surgery, postoperative complications have inevitably arisen. Chylothorax significantly affects a patient's discharge and recovery. This study investigates the risk factors for postoperative chylothorax at our center and analyzes various treatment modalities and prognostic outcomes. Methods: A retrospective analysis was conducted on all postoperative lung resections performed between January 2018 to August 2021 that met the inclusion criteria. Inclusion criteria covered patients undergoing various thoracic surgeries for lung conditions, while exclusion criteria included postoperative referrals for surgeries unrelated to lung tumors. Results: Postoperative chylothorax occurred in 42 of 5,706 patients after lung surgery. General information and disease-related data of the chylothorax and control group were analyzed by univariate and multivariate analyses. Multivariate analysis showed that serum albumin before surgery [odds ratio (OR) =0.86, 95% confidence interval (CI): 0.81-0.91, P<0.001], γ-glutamyl transferase level before surgery (after logarithmic transformation, OR =1.01, 95% CI: 1.00-1.01, P=0.01), squamous cell carcinoma (OR =2.77, 95% CI: 1.37-5.6, P=0.008), right mediastinal lymph node dissection (OR =3.15, 95% CI: 1.62-6.14, P<0.001) were independent risk factors for postoperative chylothorax. Among the 42 cases of postoperative chylothorax, 26 patients were improved with conservative treatments, and 6 patients were improved with chemical pleurodesis. Eight patients with postoperative chylothorax underwent thoracoscopic thoracic duct ligation. Three patients experienced severe postoperative complications: one was discharged after prolonged treatment, while the remaining two either succumbed or were discharged against medical advice. Conclusions: The incidence of chylothorax after lung surgery closely correlates with the intraoperative trauma and nutritional status of patients during the perioperative period. The majority of patients with postoperative chylothorax experienced relief through conservative measures, somatostatin administration, and chemical pleurodesis. Nevertheless, substantial postoperative chylothorax necessitated surgical intervention, involving thoracic duct ligation or drug pleurodesis.

Correlation analysis between driver gene mutation and clinicopathological features in lung adenocarcinoma based on real-world cumulative clinical data.

Background: Driver genes are essential predictors of targeted therapeutic efficacy. Detecting driver gene mutations in lung adenocarcinoma (LUAD) patients can help to screen for targeted drugs and improve patient survival benefits. This study aims to investigate the mutation characterization of driver genes and their correlation with clinicopathological features in LUAD. Methods: A total of 440 LUAD patients were selected from Sir Run Run Shaw Hospital between July 2019 and September 2022. Postoperative tissue specimens were analyzed for gene mutations using next-generation sequencing technology, focusing, including epidermal growth factor receptor EGFR, ALK, ROS1, RET, KRAS, MET, BRAF, HER2, PIK3CA and NRAS. At the same time, clinicopathological data were collected and organized for multidimensional correlation analysis. Results: Of 440 LUAD patients, driver gene mutations were not detected in 48 patients. The proportion of patients with driver gene mutations was as high as 89.09%. The top three driver genetic mutations were EGFR, KRAS, and MET. Sixty-nine types of EGFR mutations were detected and distributed in the protein tyrosine kinase catalytic domain (56, 81.16%), Furin-like cysteine-rich region (9, 13.04%), receptor binding domain (3, 4.35%), and EGFR transmembrane domain (1, 1.45%). Single gene locus mutation occurred in 343 LUAD patients, but the mutation gene types covered all tested genes. Our findings showed that EGFR mutations were more commonly observed in non-smoking and female patients (P<0.01), KRAS mutations were more prevalent in male patients and smokers (P<0.01), ROS1 mutations had larger tumor diameters (P<0.01) and RET mutations were more prevalent in smokers (P<0.05). Conclusions: LUAD patients exhibit diverse genetic mutations, which may co-occur simultaneously. Integrated analysis of multiple mutations is essential for accurate diagnosis and effective treatment of the disease. The use of NGS can significantly expand our understanding of gene mutations and facilitate integrated analysis of multiple gene mutations, providing critical evidence for targeted treatment methods.

A comparison of two methods of lymph node dissection along the left recurrent laryngeal nerve in McKeown minimally invasive esophagectomy.

Background: Lymph nodes dissection in esophagectomy is an essential procedure for radical resection, which can not only provide more accurate staging but may also improve survival, while it is technically challenging and may lead to recurrent laryngeal nerve (RLN) paralysis. Numerous efforts have been directed to achieve the dissection of more LNs around the RLN and to lower the incidence of RLN palsy, including Bascule method and modified Bascule method. On this basis, we modified and applied a novel method which involves the en bloc dissection of lymph nodes dissection along the left RLN in McKeown minimally invasive esophagectomy (MIE). Methods: A total of 244 consecutive cases of lymphadenectomy along the left RLN during McKeown MIE at our institution between January 2018 and August 2021 were retrospectively analyzed. The cases were divided into two groups based on the methods of lymphadenectomy along the left RLN: 77 cases received the conventional method (CM group) and 167 cases received the novel method (NM group). The surgical outcomes, especially the impact of surgical proficiency on the outcomes of lymphadenectomy along the left RLN, were assessed and compared between the two groups. Results: Demographic data of the two cohorts were similar. The number of harvested lymph nodes (LNs) (total/abdomen/left RLN) in the NM group was markedly higher than that in the CM group (32 vs. 27, P=0.006; 11 vs. 9, P=0.038; 3 vs. 2, P=0.044). However, the number of harvested LNs from the chest or right RLN was not significantly different in the two groups. The hoarseness rate was 1.8% in the NM group, which was slightly but not notably lower than that of the CM group (1.8% vs. 2.6%, P=0.681). The incidence of LN metastasis along the left RLN was 13.9%, 15.6%, and 13.2% in the whole cohort, CM group, and NM group, respectively. Conclusions: Our novel method not only increased the number of LN dissections along left RLN but also slightly reduced the incidence of hoarseness. Therefore, this novel method of lymphadenectomy along the left RLN during McKeown MIE is safe and reliable.

Genetic associations between circulating metabolic biomarkers and lung cancer in East Asians and Europeans.

BACKGROUND: Metabolic biomarkers are reported to be associated with the risk of lung cancer (LC). However, the observed associations from epidemiological studies are either inconsistent or inconclusive. METHODS: The genetic summary data of high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), total cholesterol (TC), triglyceride (TG), fasting plasma glucose (FPG), and glycated hemoglobin (HbA1c) and those of the LC and its histological subtypes were retrieved from previous GWASs. We performed two-sample Mendelian randomization (MR) and multivariable MR analyses to examine the associations between genetically predicted metabolic biomarkers and LC in East Asians and Europeans. RESULTS: In East Asians, the inverse-variance weighted (IVW) method suggests that LDL (odds ratio [OR] = 0.799, 95% CI 0.712-0.897), TC (OR = 0.713, 95% CI 0.638-0.797), and TG (OR = 0.702, 95% CI 0.613-0.804) were significantly associated with LC after correction for multiple testing. For the remaining three biomarkers, we did not detect significant association with LC by any MR method. Multivariable MR (MVMR) analysis yielded an OR of 0.958 (95% CI 0.748-1.172) for HDL, 0.839 (95% CI 0.738-0.931) for LDL, 0.942 (95% CI 0.742-1.133) for TC, 1.161 (95% CI 1.070-1.252) for TG, 1.079 (95% CI 0.851-1.219) for FPG, and 1.101 (95% CI 0.922-1.191) for HbA1c. In Europeans, the univariate MR analyses did not detect significant association between exposures and outcomes. However, in MVMR analysis integrating circulating lipids and lifestyle risk factors (smoking, alcohol drinking, and body mass index), we found that TG was positively associated with LC in Europeans (OR = 1.660, 95% CI 1.060-2.260). Subgroup and sensitivity analysis yielded similar results to the main analyses. CONCLUSIONS: Our study provides genetic evidence that circulating levels of LDL was negatively associated with LC in East Asians, whereas TG was positively associated with LC in both populations.

Deacetylation of ATG7 drives the induction of macroautophagy and LC3-associated microautophagy.

LC3 lipidation plays an important role in the regulation of macroautophagy and LC3-associated microautophagy. The E1-like enzyme ATG7 is one of the core components that are directly involved in LC3 lipidation reaction. Here, we provide evidence showing that acetylation of ATG7 tightly controls its enzyme activity to regulate the induction of macroautophagy and LC3-associated microautophagy. Mechanistically, acetylation of ATG7 disrupts its interaction with the E2-like enzyme ATG3, leading to an inhibition of LC3 lipidation in vitro and in vivo. Functionally, in response to various different stimuli, cellular ATG7 undergoes deacetylation to induce macroautophagy and LC3-associated microautophagy, which are necessary for cells to eliminate cytoplasmic DNA and degrade lysosome membrane proteins, respectively. Taken together, these findings reveal that ATG7 acetylation acts as a critical rheostat in controlling LC3 lipidation and related cellular processes.Abbreviations: AMPK: AMP-activated protein kinase; ATG: autophagy-related; cGAMP: cyclic GMP-AMP; CGAS: cyclic GMP-AMP synthase; CREBBP/CBP: CREB binding protein; EGF: epidermal growth factor; EGFR: epidermal growth factor receptor; EP300/p300: E1A binding protein p300; IFNB1: interferon beta 1; ISD: interferon stimulatory DNA; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MCOLN1/TRPML1: mucolipin TRP cation channel 1; MEF: mouse embryonic fibroblast; MTOR: mechanistic target of rapamycin kinase; NAM: nicotinamide; PE: phosphatidylethanolamine; PTM: post-translational modification; RB1CC1/FIP200: RB1 inducible coiled-coil 1; SIRT: sirtuin; SQSTM1/p62: sequestosome 1; STING1: stimulator of interferon response cGAMP interactor 1; TSA: trichostatin A; ULK1: unc-51 like autophagy activating kinase 1; WIPI2: WD repeat domain, phosphoinositide interacting 2; WT: wild-type.

Advances in efficacy prediction and monitoring of neoadjuvant immunotherapy for non-small cell lung cancer.

The use of immune checkpoint inhibitors (ICIs) has become mainstream in the treatment of non-small cell lung cancer (NSCLC). The idea of harnessing the immune system to fight cancer is fast developing. Neoadjuvant treatment in NSCLC is undergoing unprecedented change. Chemo-immunotherapy combinations not only seem to achieve population-wide treating coverage irrespective of PD-L1 expression but also enable achieving a pathological complete response (pCR). Despite these recent advancements in neoadjuvant chemo-immunotherapy, not all patients respond favorably to treatment with ICIs plus chemo and may even suffer from severe immune-related adverse effects (irAEs). Similar to selection for target therapy, identifying patients most likely to benefit from chemo-immunotherapy may be valuable. Recently, several prognostic and predictive factors associated with the efficacy of neoadjuvant immunotherapy in NSCLC, such as tumor-intrinsic biomarkers, tumor microenvironment biomarkers, liquid biopsies, microbiota, metabolic profiles, and clinical characteristics, have been described. However, a specific and sensitive biomarker remains to be identified. Recently, the construction of prediction models for ICI therapy using novel tools, such as multi-omics factors, proteomic tests, host immune classifiers, and machine learning algorithms, has gained attention. In this review, we provide a comprehensive overview of the different positive prognostic and predictive factors in treating preoperative patients with ICIs, highlight the recent advances made in the efficacy prediction of neoadjuvant immunotherapy, and provide an outlook for joint predictors.

Competition for gradient-free tuning of large language models: approaches, results, current challenges and future directions.

This perspective presents a brief overview of the background of Gradient-free tuning for large language models competition, the championship scheme, as well as the challenges and future directions.

The role of LINC01419 in regulating the cell stemness in lung adenocarcinoma through recruiting EZH2 and regulating FBP1 expression.

BACKGROUND: Recent years have witnessed a growing academic interest in the effects of lncRNAs on tumors. LINC01419 is found to facilitate proliferation and metastasis of lung adenocarcinoma (LUAD) cells, but there is a great deal of uncertainty about how LINC01419 works on LUAD cell stemness. For this reason, the focus of this research is centered on the regulatory impact of LINC01419 on LUAD cell stemness. METHODS: For the detection of the expression level of LINC01419 in LUAD, qRT-PCR was performed. And how oe-LINC01419 and sh-LINC01419 affected LUAD cell proliferation as well as stem cell sphere-formation were examined by CCK-8 and cell sphere-forming assays. In addition, whether LINC01419 could recruit EZH2 and regulate FBP1 expression were determined by bioinformatics analysis, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (ChIP). Western blot was utilized to detect the protein expression levels of FBP1, CD44, CD133, and ALDH-1 as well. RESULTS: On the basis of the findings from those assays, an up-regulation of LINC01419 level was demonstrated in LUAD cell lines, and a remarkable upregulation of it in CD44 + LUAD cells. In LUAD cells, proliferation and stem cell sphere-formation that were attenuated by LINC01419 knockdown were discovered to be facilitated by LINC01419 overexpression. And a binding relationship between LINC01419 and EZH2 was determined by RIP assay. Besides, EZH2 was capable of binding to FBP1 promoter region, as found by ChIP-PCR assay. Finally, it was demonstrated by in vitro experiments that LINC01419 could inhibit FBP1 expression by recruiting EZH2, resulting in promotion of LUAD cell proliferation and stemness. SIGNIFICANCE: To summarize, our findings demonstrate a cancer-promoting role of LINC01419 in LUAD. LINC01419, by recruiting EZH2 and regulating FBP1 expression, contributes to LUAD cell stemness. According to these findings, the potential of LINC01419 to be the target for LUAD treatment is hence determined, which also adds more possibility to the enrichment of therapeutic strategies for lung cancer stem cells.

Primary pulmonary extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type: a case report and literature review.

Primary pulmonary mucosa-associated lymphoid tissue (MALT)-derived lymphoma is a low-grade B-cell non-Hodgkin's lymphoma. It is rare with unclear clinical and imaging findings, requiring biopsy or surgery for diagnosis. Here, we provide a new case to learn the symptoms, diagnosis and treatment of primary pulmonary MALT lymphoma. The patient was a 51-year-old male. During the annual physical examination in 2019, a shadow in the lower lobe of the right lung was accidentally found in his chest computed tomography image. In 2020, the size and density of the shadows increased, which was suspected to be lung adenocarcinoma. The patient underwent video-assisted thoracoscopic surgery and segmental resection. Pathological examination showed residual germinal centers around the tumor cells, and many inflammatory cells had diffusely infiltrated, mainly monocyte-like B cells. Immunohistochemical analysis showed that CD3, CD20, Bcl-2, CD43, CK-pan and CD23 were positive, while BCL-6, CD5, CD10, c-myc and cyclin D1 were negative. The patient was diagnosed with MALT extranodal marginal zone B-cell lymphoma. The patient did not receive chemotherapy or radiotherapy after the operation but was still under close observation. Primary pulmonary MALT develops slowly and tends to be inert and spontaneous. Due to the lack of specific clinical symptoms and imaging findings, it can easily be misdiagnosed as tuberculosis, lung cancer, or infection. Thoracoscopic resection may be a good choice for the diagnosis and treatment.

Effect of Thymosin on Inflammatory Factor Levels, Immune Function, and Quality of Life in Lung Cancer Patients Undergoing Radical Thoracoscopic Surgery.

Purpose: To explore the effect of thymosin on inflammatory factor levels, immune function, and quality of life in patients undergoing radical thoracoscopic lung cancer surgery. Methods: One hundred and twenty patients admitted to the Surgical Oncology Department of the First Hospital of Jiaxing from January 2018 to January 2019 were randomized into the study group and the control group using the random number table method, with 60 cases in each group. The control group was treated with radical thoracoscopic lung cancer surgery, and the study group was treated with radical thoracoscopic lung cancer surgery combined with thymosin. The clinical efficiency, inflammatory factors, immune function, and quality of life between the two groups of patients were compared. Results: There was no significant difference between the two groups in terms of pathological stage, tissue type, maximum tumor diameter, and perioperative indicators such as operative time, intraoperative bleeding, pleural drainage, hospital stay, and the number of intraoperative lymph nodes removed. The levels of CD4 (+%), CD8 (+%), CD4+/CD8+, and natural killer cell (NK) (%) were significantly decreased in both groups after treatment, with significantly higher results in the study group than in the control group. The study group had significantly lower serum interleukin-6 (IL-6) levels and higher interleukin-10 (IL-10) levels than the control group. After treatment, patients in the study group had better postoperative physiological status and overall score than the control group. There was no significant difference in postoperative survival and adverse reactions between the two groups. Conclusion: The use of thymosin treatment in lung cancer patients undergoing radical thoracoscopic surgery significantly improves immune function, mitigates inflammatory response, and enhances the quality of life, which is worthy of clinical application.

Tissue Imprinting on 2D Nanoflakes-Capped Silicon Nanowires for Lipidomic Mass Spectrometry Imaging and Cancer Diagnosis.

Spatially resolved tissue lipidomics is essential for accurate intraoperative and postoperative cancer diagnosis by revealing molecular information in the tumor microenvironment. Matrix-free laser desorption ionization mass spectrometry imaging (LDI-MSI) is an emerging attractive technology for label-free visualization of metabolites distributions in biological specimens. However, the development of LDI-MSI technology that could conveniently and authentically reveal molecular distribution on tissue samples is still a challenge. Herein, we present a tissue imprinting technology by retaining tissue lipids on 2D nanoflakes-capped silicon nanowires (SiNWs) for further mass spectrometry imaging and cancer diagnosis. The 2D nanoflakes were prepared by liquid exfoliation of molybdenum disulfide (MoS2) with nitrogen-doped graphene quantum dots (NGQDs), which serve as both intercalation agent and dispersant. The obtained NGQD@MoS2 nanoflakes were then decorated on the tip of vertical SiNWs, forming a hybrid NGQD@MoS2/SiNWs nanostructure, which display excellent lipid extraction ability, enhanced LDI efficiency and molecule imaging capability. The peak number and total ion intensity of different lipids species on animal lung tissues obtained by tissue imprinting LDI-MSI on NGQD@MoS2/SiNWs were ∼4-5 times greater than those on SiNWs substrate. As a proof-of-concept demonstration, the NGQD@MoS2/SiNWs nanostructure was further applied to visualize phospholipids on sliced non small cell lung cancer (NSCLC) tissue along with the adjacent normal tissue. On the basis of selected feature lipids and machine learning algorithm, a prediction model was constructed to discriminate NSCLC tissues from the adjacent normal tissues with an accuracy of 100% for the discovery cohort and 91.7% for the independent validation cohort.