Single-cell RNA sequencing reveals microenvironmental infiltration in non-small cell lung cancer with different responses to immunotherapy.

BACKGROUND: Immunotherapy represents a groundbreaking and monumental achievement in the field of cancer therapy, marking a significant advancement in fighting against this devastating disease. Lung cancer has showed consistent clinical improvements in response to immunotherapy treatments, yet, it is undeniable that challenges such as limited response rates acquire resistance, and the unclear fundamental mechanisms were inevitable problems. METHODS: The cellular composition was defined and distinguished through single-cell RNA sequencing (scRNA-seq) analysis of MPR (major pathologic response) and NMPR (non-major pathologic response) samples in GSE207422, including four primary MPR samples and eight primary NMPR samples. RESULTS: We found obvious difference in CD8+ T cell population between MPR and NMPR samples, with high expression of TYMS, RRM2, and BIRC5 in NPMR samples. Meanwhile, the proportion of macrophages and tumor epithelial cells infiltration increased in the NMPR samples. We discovered biomarkers (ACTN4, ATF3, BRD2, CDKN1A, and CHMP4B) in epithelial cells which were potentially represented worse outcomes. CONCLUSIONS: By exploring the difference of tumor microenvironment (TME) in samples with different corresponding degrees of neoadjuvant immunotherapy, this research introduces a number of novel biomarkers for predicting the response of treatment and a theoretical basis for overcoming immunotherapy resistance.

Fibronectin promotes tumor angiogenesis and progression of non-small-cell lung cancer by elevating WISP3 expression via FAK/MAPK/ HIF-1α axis and activating wnt signaling pathway.

BACKGROUND: Fibronectin, an extracellular matrix protein, has been reported to be associated with heterogeneous cancer stemness, angiogenesis and progression in multiple cancer types. However, the roles and the underlying mechanism of fibronectin on the progression NSCLC need to be further elucidated. METHODS: Public dataset such as Kaplan-Meier Plotter was used to determine the prognostic significance of genes. The correlation of different protein expression in clinical and xenograft tissues was tested by immunohistochemistry experiment. Both in vitro and in vivo experiments were performed to determine the role of fibronectin on the tumor growth, metastasis, and angiogenesis in NSCLC. The activation of key signaling pathway under fibronectin was examined by WB assay. RNA-seq was applicated to screening the target gene of fibronectin. Rescue experiment was performed to confirm the role of target gene in fibronectin-mediated function in NSCLC. Finally, luciferase and CHIP assays were used to elucidate the mechanism by which fibronectin regulated the target gene. RESULTS: Our results revealed that fibronectin was up-regulated in cancer tissues compared with the normal ones in NSCLC patients. Dish- coated fibronectin enhanced the tumor growth, metastasis, and angiogenesis of NSCLC in vitro and in vivo by promoting EMT and maintaining stemness of NSCLC cells. As expected, fibronectin activated FAK and its downstream MAPK/ERK signaling pathway. WISP3 was screened as a potential target gene of fibronectin. Interestingly, WISP3 effectively activated Wnt signaling pathway, and knockdown of WISP3 effectively blocked the influence of fibronectin on the migration, invasion and vascular structure formation potential of NSCLC cells. Our data also manifested that fibronectin elevated the transcription of WISP3 gene by promoting the binding of HIF-1α to the promoter region of WISP3 in NSCLC cells. CONCLUSIONS: Our findings sketched the outline of the route for fibronectin exert its role in NSCLC, in which fibronectin activated downstream FAK and MAPK/ERK signaling pathways, and mediated the accumulation of HIF-1α. Then, HIF-1α enabled the transcription of WISP3, and subsequently promoted the activation of Wnt signaling pathway, and finally enhanced the tumor growth, metastasis, and angiogenesis in NSCLC.

Fabrication of poly (styrene-acrylate)/silver nanoparticle-graphene oxide composite antibacterial by in situ Pickering emulsion polymerization.

Graphene oxide (GO) nanosheets decorated with silver nanoparticles (AgNPs) were easily synthesized by chemical reduction, and the prepared nanocomposite was then used as a stabilizer in the Pickering emulsion polymerization of poly (styrene-acrylate) to prepare PSA/AgNPs-GO composites. The AgNPs-GO nanocomposites were fully characterized by TEM, FTIR, Raman, SEM and XPS, which demonstrated that about 5-30 nm AgNPs with spherical, octahedral and cubic structures were decorated on the surface of wrinkled GO nanosheets. TEM photos and EDS spectrum of composites showed that the transparent GO nanosheets decorated with AgNPs were covered on the surface of PSA latexes and the AgNPs were uniformly dispersed on the surface of the PSA latexes without aggregation. The average diameter of composite latexes was obviously bigger than that of PSA latexes. However, the role of surfactant and the properties of hydrophilicity decreased the average diameter and WCA of composites while increasing the additions of AgNPs-GO nanocomposites. AFM images disclosed that wrinkled GO nanosheets decorated with AgNPs dispersed on the surface of composite films. XPS data proved clearly that silver was present only in metallic form and migration occurred during film-formation. TGA curves confirmed the composite film displayed better thermal stability than that of PSA. The results of antibacterial activity revealed that composite films had exhibited antibacterial properties against both E. coli and S. aureus, and the latter showed better antibacterial efficacy than the former. The nano-silver polyacrylate coatings with antibacterial activity explored in current work have wide application in the fields of wood coatings, leather finishing, and so on.

Efficacy of immune checkpoint inhibitors in advanced non-small cell lung cancer harboring BRAF mutations.

Background: Despite immune checkpoint inhibitors (ICI) being widely used to treat patients with advanced non-small cell lung cancer (NSCLC), few studies examine the role of ICI in patients with proto-oncogene B-Raf, serine/threonine kinase (BRAF) mutations. Methods: A retrospective study was conducted for patients with BRAF-mutant NSCLC who received treatment at Shanghai Pulmonary Hospital between 2014 and 2022. Primary end point was progression-free survival (PFS). Secondary end point was best response (RECIST, version 1.1). Results: The study involved a total of 34 patients with 54 treatments recorded. The median PFS for the whole cohort was 5.8 months and the overall objective response rate (ORR) was 24%. Patients who were treated with ICI combined with chemotherapy reported a median PFS of 12.6 months and an ORR of 44%. Those who were treated with non-ICI therapy came with a median PFS of 5.3 months and an ORR of 14%. Specifically, patients had better clinical benefits with first-line ICI-combined therapy. The PFS was 18.5 months whereas that of non-ICI group was 4.1 months. The ORR was 56% in ICI-combined group and 10% in non-ICI cohort. Conclusions: The findings observed an evidential and significant susceptibility to ICIs combined therapy in patients with BRAF-mutant NSCLC, especially in first-line treatment.

Influence of Exosomes on Astrocytes in the Pre-Metastatic Niche of Lung Cancer Brain Metastases.

BACKGROUND: Lung cancer is the most common cause of cancer-related death globally. There are several reasons for this high mortality rate, including metastasis to multiple organs, especially the brain. Exosomes play a pivotal role in tumor metastasis by remodeling the microenvironment of remote target organs and promoting the pre-metastatic niche's formation. Since astrocytes are indispensable for maintaining the homeostasis of brain microenvironment, it's of great interest to explore the influence of lung cancer cell-derived exosomes on astrocytes to further understand the mechanism of lung cancer brain metastasis. RESULTS: Twenty four h after co-culture of H1299 cell-derived exosomes and SVG P12 cells, the viability of astrocytes decreased and the apoptosis increased. The levels of cytokines in the supernatant including GROα/CXCL1, IFN-γ, IL-3, IL-5, IL-15, LIF, M-CSF, NGF, PDGF, and VEGF were significantly enhanced, while IL-7 secretion was significantly reduced. Meanwhile, apoptosis-related proteins MAP2K1, TUBA1C, RELA, and CASP6 were up-regulated. And the differentially expressed proteins were involved in regulating metabolic pathways. CONCLUSION: Exosomes of H1299 could induce apoptosis of astrocytes as well as promote their secretion of cytokines that were conducive to the formation of the inflammatory microenvironment and immunosuppressive microenvironment, and affect their metabolic pathways, thus facilitating the formation of pre-metastatic niche in lung cancer brain metastases.

Pneumomediastinum and subcutaneous emphysema secondary to dental extraction: Two case reports.

BACKGROUND: Dental extraction is a common operation in oral surgery and is usually accompanied by pain, swelling, and local infection. The application of high-speed air turbines increases the comfort of alveolar surgery and makes it more minimally-invasive. However, high-speed gas can enter the subcutaneous tissue of the face and neck or even the chest and mediastinum, which is a serious iatrogenic complication. CASE SUMMARY: We describe two cases of severe subcutaneous and mediastinal emphysema caused by high-speed turbine splitting during dental extraction. The first case involved a 34-year-old man who complained of swelling of the face, mild chest tightness, and chest pain after dental extraction. Computed tomography (CT) scan showed a large amount of gas in the neck, chest wall, and mediastinum. The second case involved a 54-year-old woman who complained of swelling and pain of the neck after dental extraction. CT showed a large amount of gas collected in the neck and mediastinum. Both of them used high-speed turbine splitting during dental extraction. CONCLUSION: High-speed turbine splitting during dental extraction may lead to severe subcutaneous and mediastinal emphysema. Dentists should carefully operate to avoid emphysema. If emphysema occurs, CT can be used to improve the diagnosis. The patient should be informed, and the complications dealt with carefully.

The clinical outcome and risk factors analysis of immune checkpoint inhibitor-based treatment in lung adenocarcinoma patients with brain metastases.

Background: The data about efficacy of immunotherapy for non-small cell lung cancer with brain metastases (BMs) from real-word settings are controversial. This real-word study is aimed to evaluate the clinical outcome of immune checkpoint inhibitor (ICI)-based treatment in lung adenocarcinoma patients with brain metastases (BMs) and explore potential risk factors, with a focus on the spatial distribution of BMs as previous studies suggested spatial heterogeneity on the brain immune microenvironment. Methods: Advanced lung adenocarcinoma patients with non-oncogene-addicted, who received ICI monotherapy or plus chemotherapy, were enrolled. Efficacy was assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Intergroup comparisons were performed using Pearson's χ2 or Fisher's exact tests for categorical variables. The progression-free survival (PFS) was estimated using Kaplan-Meier method and compared using log-rank test. Cox proportional hazards model was used for multivariate analyses. Peripheral blood was collected from 15 patients with BMs. Tumor-derived exosomes in plasma were isolated by size exclusion chromatography and the cDNA library preparations for miRNA were sequenced on an Illumina Hiseq platform. Differentially expressed genes in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed. Results: A total of 198 patients were enrolled and brain metastasis occurred in 20.7% patients (N=41). Compared with patients without BMs, those with BMs had a comparable objective response rate (ORR; 29.3% vs. 43.9%; P=0.089), a lower disease control rate (DCR; 58.5% vs. 78.3%; P=0.01), and a shorter PFS (3.6 vs. 8.6 months; P=0.069). For patients with BMs, factors, including the presence of neurological symptoms, the treatment of intracranial radiotherapy, and the combination of ICI with chemotherapy, had no impact on PFS, whereas cerebellum metastasis was significantly associated with shorter PFS (2.8 vs. 13.8 months, P=0.007). Six upregulated miRNAs were identified in patients with cerebellum metastases (N=8) compared with those without (N=7). The enrichment of differentially expression genes in the KEGG pathways indicated upregulated sulfur metabolism pathway in patients with cerebellum metastases. Conclusions: For lung adenocarcinoma patients, those with BMs have inferior response to ICI-based treatment, but not significantly, and cerebellum metastasis is an independent risk factor with poor outcome for such patients, might attributing to the upregulated sulfur metabolism.

Characteristics of Notch signaling pathway and its correlation with immune microenvironment in SCLC.

OBJECTIVES: To explore the characteristics of Notch pathway in small cell lung cancer (SCLC), clarify the expression of delta-like protein 3 (DLL3) in SCLC patients undergoing surgical treatment, and explore the correlation between DLL3 expression and clinicopathological features, prognosis, and immune microenvironment. METHODS: A total of 134 patients who received surgical treatment and were diagnosed as SCLC by postoperative histopathology were enrolled. All exon gene sequencing was performed in tumor tissues and adjacent normal tissues of 28 patients to clarify the genomic characteristics of SCLC. The expressions of DLL3 and programmed cell death 1 ligand 1 (PDL1) were detected by immunohistochemistry (IHC) in 101 postoperative pathological specimens. RESULTS: Notch receptor mutations are common, but the overall mutation rate of Notch ligand family is not high and mutually exclusive. The mutation status of Notch and Notch1 gene were not related to the prognosis. Notch1 gene mutation was significantly negatively correlated with the expression of PD-L1. DLL3 was highly expressed in SCLC and had no significant correlation with prognosis. There was a positive correlation between DLL3 expression and PD-L1 expression. Patients with positive DLL3 expression and no NOTCH 1 gene mutation had higher PD-L1 expression. SCLC patients with such characteristics may be more likely to benefit from immunotherapy. CONCLUSION: This study preliminarily explored the genomic characteristics and immune microenvironment of surgical resection of SCLC in China, and found the correlation between Notch gene mutation, DLL3 expression and PD-L1 expression, which provided a new idea for selecting appropriate treatment strategies for SCLC in the future.

Final efficacy analysis, interim safety analysis, and immunogenicity of a single dose of recombinant novel coronavirus vaccine (adenovirus type 5 vector) in adults 18 years and older: an international, multicentre, randomised, double-blinded, placebo-controlled phase 3 trial.

BACKGROUND: The Ad5-nCoV vaccine is a single-dose adenovirus type 5 (Ad5) vectored vaccine expressing the SARS-CoV-2 spike protein that was well-tolerated and immunogenic in phase 1 and 2 studies. In this study, we report results on the final efficacy and interim safety analyses of the phase 3 trial. METHODS: This double-blind, randomised, international, placebo-controlled, endpoint-case driven, phase 3, clinical trial enrolled adults aged 18 years older at study centres in Argentina, Chile, Mexico, Pakistan, and Russia. Participants were eligible for the study if they had no unstable or severe underlying medical or psychiatric conditions; had no history of a laboratory-confirmed SARS-CoV-2 infection; were not pregnant or breastfeeding; and had no previous receipt of an adenovirus-vectored, coronavirus, or SARS-CoV-2 vaccine. After informed consent was obtained, 25 mL of whole blood was withdrawn from all eligible participants who were randomised in a 1:1 ratio to receive a single intramuscular dose of 0·5 mL placebo or a 0·5 mL dose of 5 × 1010 viral particle (vp)/mL Ad5-nCoV vaccine; study staff and participants were blinded to treatment allocation. All participants were contacted weekly by email, telephone, or text message to self-report any symptoms of COVID-19 illness, and laboratory testing for SARS-CoV-2 was done for all participants with any symptoms. The primary efficacy objective evaluated Ad5-nCoV in preventing symptomatic, PCR-confirmed COVID-19 infection occurring at least 28 days after vaccination in all participants who were at least 28 days postvaccination on Jan 15, 2021. The primary safety objective evaluated the incidence of any serious adverse events or medically attended adverse events postvaccination in all participants who received a study injection. This trial is closed for enrolment and is registered with ClinicalTrials.gov (NCT04526990). FINDINGS: Study enrolment began on Sept 22, 2020, in Pakistan, Nov 6, 2020, in Mexico, Dec 2, 2020, in Russia and Chile, and Dec 17, 2020, in Argentina; 150 endpoint cases were reached on Jan 15, 2021, triggering the final primary efficacy analysis. One dose of Ad5-nCoV showed a 57·5% (95% CI 39·7-70·0, p=0·0026) efficacy against symptomatic, PCR-confirmed, COVID-19 infection at 28 days or more postvaccination (21 250 participants; 45 days median duration of follow-up [IQR 36-58]). In the primary safety analysis undertaken at the time of the efficacy analysis (36 717 participants), there was no significant difference in the incidence of serious adverse events (14 [0·1%] of 18 363 Ad5-nCoV recipients and 10 [0·1%] of 18 354 placebo recipients, p=0·54) or medically attended adverse events (442 [2·4%] of 18 363 Ad5-nCoV recipients and 411 [2·2%] of 18 354 placebo recipients, p=0·30) between the Ad5-nCoV or placebo groups, or any serious adverse events considered related to the study product (none in both Ad5-nCoV and placebo recipients). In the extended safety cohort, 1004 (63·5%) of 1582 of Ad5-nCoV recipients and 729 (46·4%) of 1572 placebo recipients reported a solicited systemic adverse event (p<0·0001), of which headache was the most common (699 [44%] of Ad5-nCoV recipients and 481 [30·6%] of placebo recipients; p<0·0001). 971 (61·3%) of 1584 Ad5-nCoV recipients and 314 (20·0%) of 1573 placebo recipients reported an injection-site adverse event (p<0·0001), of which pain at the injection site was the most frequent; reported by 939 (59%) Ad5-nCoV recipients and 303 (19%) placebo recipients. INTERPRETATION: One dose of Ad5-nCoV is efficacious and safe in healthy adults aged 18 years and older. FUNDING: CanSino Biologics and the Beijing Institute of Biotechnology.

Real-world outcomes of chemo-antiangiogenesis versus chemo-immunotherapy combinations in EGFR-mutant advanced non-small cell lung cancer patients after failure of EGFR-TKI therapy.

BACKGROUND: Despite the potent efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) in the treatment of EGFR-mutant non-small cell lung cancer (NSCLC) patients, drug resistance inevitably ensues, and there remains a paucity of treatment options in clinical practice. METHODS: We identified patients with EGFR-mutant advanced NSCLC presenting to Shanghai Pulmonary Hospital and Shanghai Chest Hospital between January 2015 and December 2020 treated with chemo-antiangiogenesis or chemo-immunotherapy combinations after EGFR-TKI resistance. Patient information was collected, and the objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS) were assessed. RESULTS: A total of 144 patients who met our inclusion criteria were enrolled. Chemo-immunotherapy combinations achieved a higher objective response rate (ORR) compared with chemo-antiangiogenesis combinations (29.5% vs. 13.0%, P=0.018). The DCR was similar between the two groups (93.0% vs. 88.6%, P=0.585), as was the median PFS (7.59 vs. 6.90 months, P=0.552). In the subgroup analyses, patients who developed secondary T790M mutations after EGFR-TKI treatment were less likely to benefit from chemo-immunotherapy combinations than their T790M-negative counterparts (3.42 vs. 7.63 months, P=0.028). For patients who received chemo-antiangiogenesis combinations after TKI resistance, no significant difference was observed in the median PFS between T790M-positive and T790M-negative patients (median PFS: 5.33 vs. 7.46 months, P=0.202). Additionally, multivariate analysis showed that an elevated platelet count was independently associated with a worse PFS for both groups. CONCLUSIONS: The efficacy of chemo-immunotherapy combinations was comparable to chemo-antiangiogenesis combinations after failure of EGFR-TKI therapy. For patients harboring EGFR T790M mutations, chemo-antiangiogenesis combinations may be the preferred therapeutic option. In addition, platelet count could be a potential prognostic factor for patients after failure of EGFR-TKI therapy. Further research should be conducted on larger populations and in a prospective setting.

The structure of blood-tumor barrier and distribution of chemotherapeutic drugs in non-small cell lung cancer brain metastases.

BACKGROUND: Brain metastasis is an important cause of increased mortality in patients with non-small cell lung cancer (NSCLC). In brain metastasis, the blood-brain barrier (BBB) is frequently impaired, forming blood-tumor barrier (BTB). The efficacy of chemotherapy is usually very poor. However, the characteristics of BTB and the impacts of BTB on chemotherapeutic drug delivery remain unclear. The present study investigated the structure of BTB, as well as the distribution of routine clinical chemotherapeutic drugs in both brain and peripheral tumors. METHODS: Bioluminescent image was used to monitor the tumor load after intracranial injection of lung cancer Lewis cells in mice. The permeability of BBB and BTB was measured by fluorescent tracers of evans blue and fluorescein sodium. Transmission electron microscopy (TEM), immunohistochemistry and immunofluorescence were performed to analyze structural differences between BBB and BTB. The concentrations of chemotherapeutic drugs (gemcitabine, paclitaxel and pemetrexed) in tissues were assayed by liquid chromatography with tandem mass spectrometry (LC-MS/MS). RESULTS: Brain metastases exhibited increased BTB permeability compared with normal BBB detected by fluorescence tracers. TEM showed abnormal blood vessels, damaged endothelial cells, thick basement membranes, impaired intercellular endothelial tight junctions, as well as increased fenestrae and pinocytotic vesicles in metastatic lesions. Immunohistochemistry and immunofluorescence revealed that astrocytes were distributed surrounded the blood vessels both in normal brain and the tumor border, but no astrocytes were found in the inner metastatic lesions. By LC-MS/MS analysis, gemcitabine showed higher permeability in brain metastases. CONCLUSIONS: Brain metastases of lung cancer disrupted the structure of BBB, and this disruption was heterogeneous. Chemotherapeutic drugs can cross the BTB of brain metastases of lung cancer but have difficulty crossing the normal BBB. Among the three commonly used chemotherapy drugs, gemcitabine has the highest distribution in brain metastases. The permeability of chemotherapeutic agents is related to their molecular weight and liposolubility.

EGFR-mutant NSCLC: emerging novel drugs.

PURPOSE OF REVIEW: Despite the significant advances in EGFR-mutant nonsmall cell lung cancer (NSCLC), some challenges remain. One of the permanent and inevitable issues is the emergence of acquired resistance. Therefore, blocking the activation of EGFR pathway and overcoming drug resistance with novel agents are still in high demand. Here, we review the development of novel drugs in EGFR-mutant, advanced NSCLC, including targeting EGFR exon 20 insertion (EGFR20ins), and novel role of epidermal growth factor receptor, tyrosine kinase inhibitor (EGFR-TKIs) in early-stage NSCLC. RECENT FINDINGS: EGFR-TKIs as adjuvant therapy or neoadjuvant therapy in patients with early-stage NSCLC with EGFR-sensitizing mutations have shown promising efficacy. The resistance mechanisms of third-generation EGFR-TKIs can be divided into two types: EGFR dependent and EGFR independent. Several clinical trials have demonstrated that the addition of MET inhibitors to EGFR-TKIs was an effective option for patients who had acquired resistance to EGFR-TKIs caused by hepatocyte growth factor receptor gene (MET) amplification or overexpression. Novel compounds that selectively and potently inhibit EGFR20ins are being investigated in phase III studies. SUMMARY: A better characterization and understanding of resistance mechanisms to first-line osimertinib and adjuvant osimertinib is helpful to guide further treatment.

Comparison between the first-line and second-line immunotherapy drugs in the progression-free survival and overall survival in advanced non-small cell lung cancer: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer but with a low early diagnosis rate. With immunotherapy becomes popular in lung cancer, single immunotherapy drug treatment as the first-line or second-line plays an important role. The meta-analysis compares different clinical effects of them by overall survival (OS) and progression-free survival (PFS) because it is important to detect the best time of immunotherapy for NSCLC patients. METHODS: Randomized controlled trials (RCTs) were selected by using the Cochrane Library, Embase, PubMed and Web of science. Pool the hazard ratio (HR) and use the PFS, OS as outcomes. RESULTS: Ten RCTs were included. The pooled results indicated that first-line and second-line single immunotherapy drug treatment seems to have a tiny difference in PFS, with HR 0.79, 95% confidence interval (CI): 0.51-1.21, I2 =89% in first-line single immunotherapy drug treatment and HR 0.74, 95% CI: 0.62-0.89, I2 =84% in second-line single immunotherapy drug treatment. When it comes to OS, first-line immunotherapy drug treatment still has better effects than the second-line. In first-line single immunotherapy drug treatment, HR 0.78, 95% CI: 0.55-1.11, I2 =83%, but in second-line, HR 0.70, 95% CI: 0.64-0.76, I2 =53%. CONCLUSIONS: First-line single drug immunotherapy had the tendency better than single immunotherapy drugs used in second-line treatment.

Distribution of pathogenic bacteria in lower respiratory tract infection in lung cancer patients after chemotherapy and analysis of integron resistance genes in respiratory tract isolates of uninfected patients.

BACKGROUND: We studied the distribution of pathogenic bacteria in lower respiratory tract infection in lung cancer patients after chemotherapy and analyzed the integron resistance genes in respiratory tract isolates of uninfected patients. METHODS: Retrospective analysis was used to select sputum samples from 400 lung cancer patients after chemotherapy admitted in Fuyang People's Hospital from July 2017 to July 2019. Culture, isolation and identification of strains were conducted in accordance with the national clinical examination operating procedures. RESULTS: A total of 134 strains were identified. In 120 patients with pulmonary infection, 114 strains were cultured. Twenty strains of klebsiella pneumoniae were cultured in 280 patients without pulmonary infection. Among the 134 strains, the detection rate of gram-negative bacteria was 79.10%. The first four strains were Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Haemophilus influenzae. The gram-positive bacteria detection rate was 4.47%, mainly Staphylococcus aureus and Streptococcus. The fungus detection rate was 16.42%. The drug sensitivity results showed that the resistance rate of gram-negative bacillus to penicillin and cephalosporin was higher, and were more sensitive to carbapenem, piperacillin tazobactam and cefoperazone sulbactam. Gram-positive cocci were resistant to penicillin, macrolide and clindamycin, and sensitive to linezolid, vancomycin and rifampicin. All strains of fungal culture were candida albicans, which were sensitive to common antifungal drugs. Among the 20 strains of klebsiella pneumoniae cultured in sputum specimens of non-infected patients with lung cancer undergoing chemotherapy, 2 strains were integron-positive strains, and all of them were class I integrons. CONCLUSIONS: Lung cancer patients after chemotherapy have a high resistance to commonly used antimicrobial drugs, so it is necessary to detect the resistance of pathogenic microorganisms in clinical practice. The strains carried by patients with lung cancer without pulmonary infection during chemotherapy can isolate type I integrons, suggesting that the spread of drug resistance at gene level should be closely detected.

The efficacy and complications of computed tomography guided microwave ablation in lung cancer.

BACKGROUND: This study aimed to explore the effect and safety of computed tomography (CT) guided microwave ablation for lung cancer. METHODS: We retrospectively enrolled CT guided microwave ablation of lung cancer patients in Shanghai Pulmonary Hospital from March 2016 to September 2019. All patients were pathologically confirmed by fine needle biopsy before microwave ablation. We reviewed CT imaging of 45 patients with lung cancer before and after microwave ablation and recorded the complications. Date were analyzed by paired-samples T-test and one-way analysis of variance. RESULTS: In 45 lung cancer patients received CT guided microwave ablation, the tumor diameter changed from 2.35±0.22 cm before surgery to 2.26±0.19 cm after surgery, average reduction by 0.09 cm (P=0.518). With microwave ablation treatment, the disease control rate reached 82.93%, and the incidence of pneumothorax was 13.3%, with no other related adverse. The successful rate of operation was 100%, and there was no severe or death related adverse. CONCLUSIONS: CT-guided microwave ablation is an effective method in the treatment of lung cancer, with a low incidence of complications. It is a safe and effective method for the treatment of lung cancer.

Expression of PD-1 and PD-L1 on Tumor-Infiltrating Lymphocytes Predicts Prognosis in Patients with Small-Cell Lung Cancer.

INTRODUCTION: Immune therapy has shown good results in small-cell lung cancer (SCLC), but the impact of immune microenvironment of the disease is unclear. In this work, we detected expression of programmed death 1 (PD-1), PD-ligand 1 (PD-L1), and other immune biomarkers of cancer. We also analyzed the correlations between these markers and survival in SCLC. PATIENTS AND METHODS: Protein expression of PD-1, PD-L1, PD-L2, CD3, CD4, CD8, and FOXP3 was analyzed in surgical tissues from 102 SCLC patients by immunohistochemistry. RESULTS: Positive expression of PD-1 on tumor-infiltrating lymphocytes (TILs) was found in 40.2% of patients; 37.3% of patients showed positive expression of PD-L1 on TILs; and 3.9% showed positive expression of PD-L1 on tumor cells. PD-L2 protein was not expressed on tumor cells or TILs. Survival analysis showed that positive expression of PD-L1 on TILs was correlated with longer relapse-free survival (RFS) (p=0.004). Positive expression of PD-1 combined with a high ratio of lymphocytes (CD3, p=0.004; CD4, p=0.011; CD8, p=0.009; FOXP3, p=0.009) was associated with significantly better RFS than negative expression of PD-1 combined with a lower ratio of lymphocytes. Positive expression of PD-L1 combined with a high ratio of lymphocytes (CD3, p<0.001; CD4, p=0.001; CD8, p=0.002; FOXP3, p=0.001) was associated with significantly better RFS than negative expression of PD-L1 combined with a lower ratio of lymphocytes. All patients' stage were between I and III. CONCLUSION: PD-1 and PD-L1 expression might be good prognostic factors in SCLC.

Mechanisms of drugs-resistance in small cell lung cancer: DNA-related, RNA-related, apoptosis-related, drug accumulation and metabolism procedure.

Small-cell lung cancer (SCLC), the highest malignant cancer amongst different types of lung cancer, has the feature of lower differentiation, rapid growth, and poor survival rate. Despite the dramatically initial sensitivity of SCLC to various types of treatment methods, including chemotherapy, radiotherapy and immunotherapy, the emergence of drugs-resistance is still a grandly clinical challenge. Therefore, in order to improve the prognosis and develop new therapeutic approaches, having a better understanding of the complex mechanisms of resistance in SCLC is of great clinical significance. This review summarized recent advances in understanding of multiple mechanisms which are involved in the resistance during SCLC treatment, including DNA-related process, RNA-related process, apoptosis-related mechanism, and the process of drug accumulation and metabolism.

cGAS-STING, an important pathway in cancer immunotherapy.

Cytosolic DNA sensing, the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, is an important novel role in the immune system. Multiple STING agonists were developed for cancer therapy study with great results achieved in pre-clinical work. Recent progress in the mechanical understanding of STING pathway in IFN production and T cell priming, indicates its promising role for cancer immunotherapy. STING agonists co-administrated with other cancer immunotherapies, including cancer vaccines, immune checkpoint inhibitors such as anti-programmed death 1 and cytotoxic T lymphocyte-associated antigen 4 antibodies, and adoptive T cell transfer therapies, would hold a promise of treating medium and advanced cancers. Despite the applications of STING agonists in cancer immunotherapy, lots of obstacles remain for further study. In this review, we mainly examine the biological characters, current applications, challenges, and future directions of cGAS-STING in cancer immunotherapy.