The increasing number of pulmonary nodules being detected by computed tomography scans significantly increase the workload of the radiologists for scan interpretation. Limitations of traditional methods for differential diagnosis of pulmonary nodules have been increasingly prominent. Artificial intelligence (AI) has the potential to increase the efficiency of discrimination and invasiveness classification for pulmonary nodules and lead to effective nodule management. Chinese Experts Consensus on Artificial Intelligence Assisted Management for Pulmonary Nodule (2022 Version) has been officially released recently. This article closely follows the context, significance, core implications, and the impact of future AI-assisted management on the diagnosis and treatment of pulmonary nodules. It is hoped that through our joint efforts, we can promote the standardization of management for pulmonary nodules and strive to improve the long-term survival and postoperative life quality of patients with lung cancer.

Objective:To provide a promising and optimal laboratory susceptibility-testing method for the clinical usage of antibiotic (polymyxin), four susceptibility-testing methods were performed and the broth microdilution (BMD) was chosen as the gold standard.Methods:A total number of eighty-eight nonduplicate clinical Enterobacteriaceae specimes were collected from January to December of 2019 in the First Affiliated Hospital, Fujian Medical University. Among the clinical specimens, of which six strains were positive for mcr-1. The minimal inhibitory concentration (MIC) of polymyxin of the clinical specimens were examined by the following methods: (1) broth microdilution, (2) colistin broth disk elution, (3) Vitek-2?, (4)BD PhoenixTM,(5)commercial broth microdilution. With BMD as reference, essential agreement (EA), categorical agreement(CA), very major error(VME) and major error (ME) of polymyxins for different methods were analyzed. The Kappa-consistency testing, paired Chi-square testing and the Spearman-rank correlation testing were used to analyze the consistency between the four antimicrobial susceptibility testing methods and the gold standard.Results:Taking broth microdilution as reference, the EA of colistin broth disk elution, Vitek-2?, BD PhoenixTM, commercial broth microdilution were 94.32% (83/88), 92.05% (81/88), 90.90% (80/88), and 96.59%(85/88), respectively. The CA of all the four methods were 100% (88/88). No VME and ME were recorded for four methods. Moreover, the consistency between four susceptibility testing methods and the gold standard is acceptable (Kappa values=1, P<0.001, McNemar test P=1 and r>0.5, P<0.05). Conclusions:In the present work, four susceptibility testing methods all met the standards recommended jointly by the Clinical and Laboratory Standards Institute and European Committee on Antimicrobial Susceptibility Testing, of which the performance of the commercial broth microdilution and CBDE fared relatively well. Thus, these four methods could be routinely used in clinical microbiology laboratory of our hospital for colistin and polymyxin B susceptibility testing.

BACKGROUND: It is a great challenge for surgeons to resect pulmonary nodules with small volume, deep position and no solid components under video-assisted thoracoscopic surgery. The purpose of this study is to explore the feasibility and necessity of the localization of pulmonary nodules by injecting indocyanine green (ICG) under the guidance of magnetic navigation bronchoscope and the resection of small pulmonary nodules under the fluoroscope. METHODS: Between December 2018 and August 2019, sixteen consecutive patients with 30 peripheral lung lesions in our hospital received fluorescent thoracoscopic pulmonary nodule resection. Electromagnetic navigation bronchoscope (ENB) was performed before surgery to guide ICG to the target lesion. RESULTS: All patients underwent magnetic navigation-guided pulmonary nodule localization, and surgical resection was performed immediately after localization was completed. The average size of the nodules was (11.12±3.65) mm. The average navigation time was (12.06±2.74) minutes, and the average interval between dye labeling and lung resection was (25.00±5.29) minutes. All lesions were completely resected, the localization success rate was 100.00%, no bleeding and other complications occurred after the localization, the postoperative pathological results confirmed the accuracy of the staining. CONCLUSIONS Indocyanine green injection under the guidance of magnetic navigation bronchoscope is an effective way to locate pulmonary nodules, which can locate small and untouchable lesions in the lung. This method can help surgeons identify lesions more quickly and accurately. It is practical and worthy of promotion.

Objective:To investigate the role of endoplasmic reticulum stress (ERS) in the autophagy of RAW264.7 cells induced by SiO 2 and its effect on the secretion of tumor necrosis factor-α. Methods:RAW264.7 cells stimulated by 200 μg/ml SiO 2 were used as an vitro cell model, and different treatment times of SiO 2 were used as variables. They were divided into 0 h treatment group (blank control group) , 6 h, 12 h, 24 h, and 48 h treatment group. The formation of autophagospores was detected by acridine orange and mondane-sulfonate (MDC) staining. Application of real-time quantitative PCR (Real-time PCR) to detect autophagy related molecular Beclin1 mRNA expression and protein immunoblot (Western Blotting) detecting autophagy related proteins LC3Ⅰ, LC3Ⅱ and expression of Beclin1. Real-time PCR and Western blotting were used to detect the expression of ERS specific marker BiP. Secretion of RAW 264.7 cell transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) was detected by enzyme-linked immunosorbent assay (ELISA) . ERS inhibitors 4-PBA intervention experiment, including blank control group, SiO 2, 1 μmol/L 4-PBA+SiO 2, 10 μmol/L 4-PBA+SiO 2, 20 μmol/L 4-PBA+SiO 2 treatment group, Western blotting testing LC3Ⅰ, LC3Ⅱ and expression of Beclin1 changes. Results:Compared with the control group, SiO 2-induced fluorescence intensity in RAW264.7 cells was significantly increased, with statistically significant differences ( P<0.05) . Compared with control group, with SiO 2 processing time prolonged, LC3Ⅰ, LC3Ⅱ Beclin1 mRNA and protein expression and protein expression increased, 6 h, 24 h, the height of the differences were statistically significant ( P<0.05) ; Compared with the control group, the mRNA and protein expression level of BiP reached the peak for 6 h, and the expression level in 6 h, 12 h and 24 h groups increased significantly, and the difference was statistically significant ( P<0.05) . Compared with the SiO 2 stimulation group, the LC3Ⅱand Beclin 1 protein levels of RAW264.7 cells were gradually down-regulated by increasing the dose of 4-PBA. With the increase of 4-PBA concentration, the down-regulated levels were more significant, and the difference was statistically significant ( P<0.05) . Compared with the SiO 2 stimulation group, the TNF-α secretion level of RAW264.7 cells significantly decreased of 1, 10, 20 μmol/L 4-PBA+SiO 2 treatment group, and the difference was statistically significant ( P<0.05) . Conclusion:ERS induced by SiO 2 is involved in the secretion of autophagy and TNF-α in RAW264.7 cells.

Objective:To investigate the role of endoplasmic reticulum stress (ERS) in the autophagy of RAW264.7 cells induced by SiO 2 and its effect on the secretion of tumor necrosis factor-α. Methods:RAW264.7 cells stimulated by 200 μg/ml SiO 2 were used as an vitro cell model, and different treatment times of SiO 2 were used as variables. They were divided into 0 h treatment group (blank control group) , 6 h, 12 h, 24 h, and 48 h treatment group. The formation of autophagospores was detected by acridine orange and mondane-sulfonate (MDC) staining. Application of real-time quantitative PCR (Real-time PCR) to detect autophagy related molecular Beclin1 mRNA expression and protein immunoblot (Western Blotting) detecting autophagy related proteins LC3Ⅰ, LC3Ⅱ and expression of Beclin1. Real-time PCR and Western blotting were used to detect the expression of ERS specific marker BiP. Secretion of RAW 264.7 cell transforming growth factor-β1 (TGF-β1) and tumor necrosis factor-α (TNF-α) was detected by enzyme-linked immunosorbent assay (ELISA) . ERS inhibitors 4-PBA intervention experiment, including blank control group, SiO 2, 1 μmol/L 4-PBA+SiO 2, 10 μmol/L 4-PBA+SiO 2, 20 μmol/L 4-PBA+SiO 2 treatment group, Western blotting testing LC3Ⅰ, LC3Ⅱ and expression of Beclin1 changes. Results:Compared with the control group, SiO 2-induced fluorescence intensity in RAW264.7 cells was significantly increased, with statistically significant differences ( P<0.05) . Compared with control group, with SiO 2 processing time prolonged, LC3Ⅰ, LC3Ⅱ Beclin1 mRNA and protein expression and protein expression increased, 6 h, 24 h, the height of the differences were statistically significant ( P<0.05) ; Compared with the control group, the mRNA and protein expression level of BiP reached the peak for 6 h, and the expression level in 6 h, 12 h and 24 h groups increased significantly, and the difference was statistically significant ( P<0.05) . Compared with the SiO 2 stimulation group, the LC3Ⅱand Beclin 1 protein levels of RAW264.7 cells were gradually down-regulated by increasing the dose of 4-PBA. With the increase of 4-PBA concentration, the down-regulated levels were more significant, and the difference was statistically significant ( P<0.05) . Compared with the SiO 2 stimulation group, the TNF-α secretion level of RAW264.7 cells significantly decreased of 1, 10, 20 μmol/L 4-PBA+SiO 2 treatment group, and the difference was statistically significant ( P<0.05) . Conclusion:ERS induced by SiO 2 is involved in the secretion of autophagy and TNF-α in RAW264.7 cells.

Objective    To evaluate the prognosis of benign esophageal perforation by Pittsburgh scoring system (perforation severity scores, PSS) combined with co-disease index (Charlson comorbidity index, CCI). Methods    Thirty patients with benign esophageal perforation from August 2016 to August 2018 in our hospital diagnosed by imaging or endoscopy were selected, including 14 males and 16 females, aged 68.660±10.072 years. After treatment, we retrospectively analyzed whether there was any complication in the course of treatment, the healing of esophageal perforation at discharge and the follow-up after discharge. And the patients were divided into a stable group (20 patients with no complication, clear healing of esophageal perforation at discharge or death during follow-up) and an unstable condition group (10 patients with complications, esophageal perforation at discharge or death during follow-up). Complete clinical data of all the patients were obtained and were able to be calculated by the scores of PSS and CCI scoring system. The difference of PSS and CCI scores between the two groups was compared, and the clinical value of PSS combined with CCI score in the prognosis of benign esophageal perforation was analyzed. Results    In the stable group, the PSS was 2.750±1.372 (95%CI 2.110 to 3.390), CCI score was 2.080±1.055 (95%CI 1.650 to 2.500) with a statistical difference between the two systems (P=0.000). In the unstable group, PSS was 7.300 ±1.829 (95%CI 7.300 to 8.120), CCI was 4.640±1.287 (95%CI 4.220 to 5.060) with a statistical difference between the two systems (P<0.05). The area under the receiver operating characteristic  curve of PSS and CCI scores in the prognostic evaluation of benign esophageal perforation was 0.982 and 0.870 respectively, which was statistically significant (P<0.05). Conclusion    Esophageal perforation is a dangerous condition. It is of great practical value to evaluate the condition of esophageal perforation by PSS and CCI scores.

To analyze the differential expression of RAW264.7 macrophage-derived exosomes miRNA stimulated by free silicon dioxide (SiO2).
 Methods: RAW264.7 was stimulated with SiO2 (200 mg/L) for 48 h (exo_48 h group), and the supernatant was collected. The exosomes in the supernatant were extracted by ultracentrifugation. Transmission microscopy, nanoparticle tracking analysis (NTA) and Western blotting were used to identify exosomes. High-throughput sequencing was performed to compare the differential expression of exosome miRNAs between the exo_control group (RAW264.7 cultured for 48 h without SiO2) and the exo_48 h group; miRanda, TargetScan and starBase were used to predict target genes of differential miRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed on target genes to further analyze the biological functions of genes.
 Results: The transmission microscopy showed that the exosomes were lipid membrane coated vesicles, which were heterogeneously distributed, with a diameter ranging from 30 to 100 nm, and the shape was round or elliptical. The volume kurtosis was concentrated between 40 and 100 nm and the exosome marker protein TSG101 was positive. High-throughput sequencing screened 148 differentially expressed exosomal miRNAs. MiR-219c-3p, let-7d-3p, let-7a-1-3p, miR-328-3p, miR-365-3p, and miR-7219-3p were significantly up-regulated, and miR-378d and miR-5106 were significantly down-regulated compared with the control group. Target genes were mainly enriched in mTOR signaling pathway, Wnt signaling pathway, TGF-β signaling pathway, and so on.
 Conclusion: The exosomes secreted by SiO2-induced macrophages contain abundant miRNAs, and their expressions are significantly different. These differential miRNAs may be involved in the activation of lung fibroblasts and epithelial-mesenchymal transition.
Animals ; Cell Line ; Exosomes ; High-Throughput Nucleotide Sequencing ; Macrophages ; Mice ; MicroRNAs ; Silicon Dioxide

Objective: To understand the consistency of ALK Ventana-D5F3 immunohistochemistry (IHC) interpretation in Chinese lung adenocarcinoma among histopathologists from different hospitals, and to recommend solution for the problems found during the interpretation of ALK IHC in real world, with the aim of the precise selection of patients who can benefit from ALK targeted therapy. Methods: This was a multicenter and retrospective study. A total of 109 lung adenocarcinoma cases with ALK Ventana-D5F3 IHC staining were collected from 31 lung cancer centers in RATICAL research group from January to June in 2018. All cases were scanned into digital imaging with Ventana iSCANcoreo Digital Slide Scanning System and scored by 31 histopathologists from different centers according to ALK binary (positive or negative) interpretation based on its manufacturer′s protocol. The cases with high inconsistency rate were further analyzed using FISH/RT-PCR/NGS. Results: There were 49 ALK positive cases and 60 ALK negative cases, confirmed by re-evaluation by the specialist panel. Two cases (No. 2302 and No.2701) scored as positive by local hospitals were rescored as negative, and were confirmed to be negative by RT-PCR/FISH/NGS. The false interpretation rate of these two cases was 58.1% (18/31) and 48.4% (15/31), respectively. Six out of 31 (19.4%) pathologists got 100% accuracy. The minimum consistency between every two pathologists was 75.8%.At least one pathologist gave negative judgement (false negative) or positive judgement (false positive) in the 49 positive or 60 negative cases, accounted for 26.5% (13/49), 41.7% (25/60), respectively, with at least one uncertainty interpretation accounted for 31.2% (34/109). Conclusion There are certain heterogeneities and misclassifications in the real world interpretation of ALK-D5F3 IHC test, which need to be guided by the oncoming expert consensus based on the real world data.

Objective The study aims to investigate the associationbetweencholesterol 7α-hydroxylase (CYP7A1) gene polymorphism and different clinical outcomes after Hepatitis B virus (HBV)infection in Fujian Han population and lay a foundation for understanding the mechanisms of genesis anddevelopment of HBV-related diseases.Methods Case-control study was conducted.586 patients of HBVpersistent infection without antiviral therapy and 225 HBV rehabilitation patients (35-55 years old) werecollected from May 2015 to June 2016 in the Liverish Center of First Clinical College of Fujian MedicalUniversity.The group of HBV persistent infection without antiviral therapy included 246 patients with chronichepatitis B, 177 patients with hepatitis B-related cirrhosis, and 163 patients with hepatitis B-related liver cancer.The rs3824260, rs4738687and rs8192871 loci of CYP7A1 gene were detected by improved multipleligase detection reaction (iMLDR).Logistic regression analysis and chi-square test were used to analyze thegenotyping results.Results Three SNPs ( single nucleotide polymorphisms ) of CYP7A1 gene wereselected and compared between HBV persistent infection group and HBV rehabilitation group and betweenchronic hepatitis B subgroup, liver cirrhosis subgroup and liver cancer subgroup.After adjustment for factorsincluding age andgender, there was no significant difference in the distribution of rs3824260 genotype amongthe groups(χ2 =1.565,P =0.459), however,the frequency of allele C in HBV rehabilitation group wassignificantly higher than in HBV persistent in fectiongroup for men (χ2 =4.365,P =0.037), whereas thefrequency of rs3824260 CC and CT was more likely to be observed in liver cancer group than in non -livercancer group (chronic hepatitis B subgroup and liver cirrhosis subgroup ) for women (χ2 =5.768,P =0.012;χ2 =10.130,P =0.001).The frequency of rs4738687 GG genotype was more likely to be observed innon-liver cancer group than in liver cancer group (χ2 =4.403,P =0.041;χ2 =6.940,P =0.009).Theresults of gender stratification showed that there were significant differences in the distribution of rs 4738687among the HBV persistent infection groups for men (χ2 =10.697,P =0.030), however, there was nosignificant difference in the distribution of rs4738687 among the HBV persistent infection groups for women(χ2 =4.627,P =0.329), and there was no significant difference in the distribution of genotype frequencyand allele frequency among all groups(χ2 =0.489,P =0.792).There was no significant difference after sexstratification either (χ2 =1.282, P =0.526;χ2 =1.565,P =0.465) .Conclusions These findingssuggested that CYP7A1 gene polymorphism was related todifferent clinical outcomes in Fujian Hanpopulation.The rs3824260 mutation had a certain gender preference and the mutation allele was detected ina higher proportion in male patients.Male HBV patients with rs3824260 C allele had more chance ofswitching to rehabilitation.The rs4738687 was likely to be related to the occurrence of liver cancer in FujianHan population, and GG genotype may delay the occurrence and development of liver cancer especially in themale group.The rs8192871 was not found to be related to the different clinical outcomes of HBV infection.

Objective To investigate the epidemiological and molecular virological characteristics in HBV-infected patients with copositive HBsAg and anti-HBs.Methods HBV serological markers were analyzed in 52 070 specimens.The epidemiological characteristics of HBsAg and anti-HBs simultaneously positive patients (the experimental group) and HBsAg positive and auti-HBs negative patients (the control group) were compared.The S protein of HBV coding region was amplified by semi-nested PCR and sequenced.The statistical differences between the two groups were compared in different gene regions,genotypes and different clinical diagnosis.Results HBsAg was positive in 20.40％ (10 621/52 070) of all specimens.In the patients with positive HBsAg,2.48％ (263/10 621) was positive anti-HBs.The prevalence of co-positive HBsAg and auti-HBs was higher in aged 0 to 9 years and greater than or equal to 80 years than that in other age,and the prevalence of positive HBsAg and negative anti-HBs was completely opposite.The mutation rate of S protein in the experimental group was significantly higher than that in the control group (1.52％ vs 0.81％,P ＜0.01) with the mutation in the major hydrophilic region (MHR) (1.68％ vs 0.57％,P ＜0.01).The mutation rates of S protein of HBV carriers,chronic hepatitis B (CHB) patients and patients with liver cirrhosis (LC) in the experimental group were significantly higher than those in the control group (1.47％ vs 0.65％,1.28％ vs 0.84％,2.21％ vs 0.44％,P ＜0.05,respectively),except for the patients with hepatocellular carcinoma (HCC) (1.97％ vs 2.21％,P ＞ 0.05).Conclusion Co-positive HBsAg and anti-HBs in HBV-infected patients was more common in HBsAg positive patients aged 0 to 9 years and greater than or equal to 80 years than the others.Coexistence of HBsAg and anti-HBs in HBV-infected patients may relate to immune escape caused by mutation of S protein (mainly MHR).The mutation rates of S protein in the two groups of patients,co-positive HBsAg and anti-HBs and the positive HBsAg combined with negative anti-HBs,were associated with the stage of liver disease.