Perovskite Probe-Based Machine Learning Imaging Model for Rapid Pathologic Diagnosis of Cancers.

Accurately distinguishing tumor cells from normal cells is a key issue in tumor diagnosis, evaluation, and treatment. Fluorescence-based immunohistochemistry as the standard method faces the inherent challenges of the heterogeneity of tumor cells and the lack of big data analysis of probing images. Here, we have demonstrated a machine learning-driven imaging method for rapid pathological diagnosis of five types of cancers (breast, colon, liver, lung, and stomach) using a perovskite nanocrystal probe. After conducting the bioanalysis of survivin expression in five different cancers, high-efficiency perovskite nanocrystal probes modified with the survivin antibody can recognize the cancer tissue section at the single cell level. The tumor to normal (T/N) ratio is 10.3-fold higher than that of a conventional fluorescent probe, which can successfully differentiate between tumors and adjacent normal tissues within 10 min. The features of the fluorescence intensity and pathological texture morphology have been extracted and analyzed from 1000 fluorescence images by machine learning. The final integrated decision model makes the area under the receiver operating characteristic curve (area under the curve) value of machine learning classification of breast, colon, liver, lung, and stomach above 90% while predicting the tumor organ of 92% of positive patients. This method demonstrates a high T/N ratio probe in the precise diagnosis of multiple cancers, which will be good for improving the accuracy of surgical resection and reducing cancer mortality.

Initial experience with robotic-assisted thoracic surgery for superior mediastinal masses.

Objective: Minimally invasive surgery is challenging for masses located in the superior mediastinum, especially for those close to the chest outlet. This study aimed to evaluate the feasibility and safety of robotic-assisted thoracic surgery (RATS) for these masses. Methods: From June 2015 to January 2020, 35 patients (19 males, 16 females), with a mean age of 41.6 (range, 13-66) years, underwent RATS for the treatment of superior mediastinal masses. Data regarding the operation time, blood loss, pathology, conversion rate, morbidity, mortality, and cost were collected and analyzed. Results: The mean (±standard deviation) operation time, blood loss, chest tube use duration, and postoperative hospital day were 117 ± 45.2 (range, 60-270) min, 59.7 ± 94.4 (range, 10-500) ml, 4.1 ± 2.1 (range, 1-10) days, and 5.1 ± 2.1 (range, 2-11) days, respectively. The pathological diagnoses included schwannoma (26 cases), ganglioneuroma (4 cases), bronchogenic cysts (3 cases), ectopic nodular goiter (1 case), and cavernous hemangioma (1 case). The mean diameter of the resected tumor was 4.6 ± 2.0 (range, 2.5-10) cm. No conversion or mortality occurred. Postoperative complications included Horner's syndrome (18 cases: 6 patients with preoperative Horner's syndrome), weakened muscular power (2 cases), and chylothorax (2 cases). The mean cost was $ 8,868.7 (range, $ 4,951-15,883). Conclusions: Our experience demonstrated that RATS is safe and feasible for superior mediastinal mass resection. However, the high incidence of postoperative Horner's syndrome requires further research.

Clinical Analysis of Video-Assisted Thoracoscopic Surgery for Resection of Solitary Pulmonary Nodules and Influencing Factors in the Diagnosis of Benign and Malignant Nodules.

PURPOSE: This is a retrospective research comparing the clinical outcomes of single-hole versus multi-hole video-assisted thoracoscopic surgical (VATS) resection for solitary pulmonary nodules (SPN) and examining the factors influencing the diagnosis of benign and malignant pulmonary nodules. METHOD: We collected the clinical data, surgical status, outcomes, and corresponding imaging features of 317 patients with SPN who were surgically resected by VATS and diagnosed as benign or malignant by pathology in our hospital from January 2019 to December 2021. RESULT: Among the 317 patients, 124 (39.12%) underwent single-port VATS and 193 (60.88%) underwent multiple-hole VATS. All patients were grouped according to the different surgical methods, and their postoperative indicators were statistically analyzed. The results showed that neither the single-port VATS group nor the multi-port VATS group had any serious adverse events such as death during the perioperative period. The average operation time, intraoperative blood loss, drainage tube indwelling time, and postoperative hospital stay were significantly lower in the two groups. Statistics of postoperative pathological diagnosis showed that 98 cases (30.91%) of all nodules were benign nodules and 219 cases (69.09%) were malignant nodules, and a further single-multivariate analysis showed that age, nodule maximum diameter, lobular sign, burr sign, vascular cluster sign, and pleural depression sign were independent relevant factors for the diagnosis of benign and malignant nodules. CONCLUSION: VATS is less invasive and has fewer complications and is of great clinical value for both diagnosis and treatment of benign and malignant SPN. Age, maximum nodal diameter, lobar sign, burr sign, vascular set sign, and pleural depression sign were independent correlates affecting the diagnosis of benign and malignant SPN, which reminds that great attention should be paid to patients who are older and have risk factors on imaging, and early and timely active treatment or close follow-up should be carried out.

The expression of mouse double minute 2 homolog and P73 had no correlation with growth arrest DNA damage-inducible gene 45α in patients with non-small-cell lung carcinoma: A STROBE-compliant study.

To investigate the difference in messenger ribonucleic acid (mRNA) and protein expression of growth arrest DNA damage-inducible gene 45α (GADD45α), mouse double minute 2 homolog (MDM2), and P73 in cancer and cancer-adjacent tissues in patients with non-small-cell lung carcinoma (NSCLC).We compared the mRNA expression of GADD45α and MDM2 and the protein expression of GADD45α, MDM2, and P73 in lung cancer and cancer-adjacent tissues in NSCLC patients by quantitative real-time PCR, immunohistochemistry (IHC), and Western Blot (WB). We analyzed GADD45α, MDM2, and P73 expression in patients with different pathological types of NSCLC, and the correlation of these genes with gender, smoking history, and TNM/T stages.IHC results suggested that MDM2 protein expression significantly increased in cancer tissues in female patients (P = .01), but not in male patients. In addition, WB results indicated that P73 protein expression significantly decreased in cancer tissues in patients with adenocarcinoma (P = .03), but not squamous carcinoma.MDM2 and P73 protein levels were differentially regulated in cancer and cancer-adjacient tissues in patients with sub types of NSCLC. There was no significant difference in GADD45α expression between cancer and cancer-adjacent tissues in NSCLC patients.

Bisphenol S (BPS) triggers the migration of human non-small cell lung cancer cells via upregulation of TGF-ß.

As one of the leading causes of cancer deaths world-wide, the progression of human non-small cell lung cancer (NSCLC) can be regulated by estrogenic signals. Our present data showed that an industrial endocrine disrupting chemical, bisphenol S (BPS), can promote the in vitro migration of NSCLC cells, which was evidenced by the upregulation of vimentin and matrix metalloproteinase-2 (MMP-2). BPS can increase the mRNA and protein expression of IL-10 and TGF-ß. While only targeted inhibition of TGF-ß can block BPS induced migration of NSCLC cells. The upregulation of TGF-ß can further activate the Smad-2/3 pathways. Further, BPS induced expression of TGF-ß was ERα/ß or G protein-coupled estrogen receptor (GPER) independent, since targeted inhibition of ERα/ß or GPER had no effect on BPS induced transcription of TGF-ß. We identified that the inhibitor of ERK1/2 can attenuate BPS induced expression of TGF-ß and activation of Smad-2/3 pathways. Collectively, we found that nanomolar BPS can trigger the in vitro migration of NSCLC cells via ERK1/2 mediated activation of TGF-ß/Smad-2/3 pathways.

Prognostic significance of NFIA and NFIB in esophageal squamous carcinoma and esophagogastric junction adenocarcinoma.

The nuclear factor I (NFI) family members, especially NFIA and NFIB, play essential roles in cancers. The roles of NFIA and NFIB in esophageal squamous cell carcinoma (ESCC) and esophagogastric junction adenocarcinoma (EJA) remain poorly known. This study aimed to determine the expression of NFIA and NFIB in ESCC and EJA and elucidate their prognostic significance. The expression of NFIA and NFIB was examined in 163 ESCC samples and 26 EJA samples by immunohistochemistry. The results showed that high NFIA expression correlated significantly with poor differentiation, lymph node metastasis, and advanced TNM stage in patients with ESCC. High NFIB expression only correlated with poor differentiation in patients with ESCC. Survival analysis showed that NFIA but not NFIB associated with short overall survival (OS) and disease-free survival (DFS) of patients with ESCC. On the other hand, high NFIB expression correlated with lymph node metastasis, advanced TNM stage, and short OS and DFS in patients with EJA. Finally, multivariate analysis demonstrated that high NFIA expression was an independent prognostic factor for ESCC. Taken together, these results demonstrated that NFIA and NFIB could serve as prognostic indicators for ESCC and EJA, respectively.

Inhibition of human lung cancer proliferation through targeting stromal fibroblasts by dihydromyricetin.

In the present study, the effects of dihydromyricetin on the proliferative potential of fibroblasts and lung carcinoma cells were investigated. Markedly higher expression levels of smooth muscle actin and platelet derived growth factors (PDGFs) were observed in the fibroblasts using reverse transcription-polymerase chain reaction analysis. The expression levels of PDGF-A and PDGF-B were also higher in the lung cancer cells. Western blot analysis revealed higher expression levels of the receptor for platelet-derived growth factor (PDGFRß) in the lysates from fibroblasts obtained from normal tissues and carcinoma tissues. Treatment of the fibroblasts with dihydromyricetin inhibited the expression of PDGFRß when treated with a 10 µM concentration for 48 h. Treatment of the fibroblasts with a 10 µM concentration of dihydromyricetin for 48 h led to complete inhibition of the activation of extracellular signal-regulated kinase (Erk)1/2 and Akt. The results of an MTT assay showed that treatment of the fibroblasts with dihydromyricetin significantly reduced the PDGF-mediated increase in the rate of proliferation. The rate of proliferation of the A549 lung cancer cells cultured with fibroblasts was markedly increased, compared with that of the A549 cells cultured alone. However, dihydromyricetin significantly (P<0.05) inhibited the proliferation rate of the A549 cells cultured with fibroblasts, compared with the untreated cultures. The proliferation rates of the A549 cancer cells, A549 cells cultured with fibroblasts, and A549 cells cultured with fibroblasts and treated with dihydromyricetin were found to be were 78.45, 98.45 and 21.37%, respectively. Dihydromyricetin inhibited the proliferative potential of fibroblasts in the lung cancer cells through targeting the activation of Erk1/2 and Akt. Therefore, there is scope for dihydromyricetin to be evaluated further for the treatment of lung cancer.

The MDM2 T309G polymorphism and risk of lung cancer: an updated meta-analysis of 10,186 cases and 14,155 controls.

INTRODUCTION: The aim of this paper was to assess the relationship between MDM2 (mouse double minute 2 homolog) T309G polymorphism and the risk and prognosis of lung cancer. EVIDENCE ACQUISITION: We did a systematic review of relevant articles from EBSCO, EMBASE, Web of science, PubMed, springer link, science direct, weipu database and CNKI (Chinese National Knowledge Infrastructure) databases up to January 7, 2016. EVIDENCE SYNTHESIS: Seventeen case-control studies and 5 cases prognosis were included. The results indicated that the MDM2 T309G polymorphism was associated with lung cancer risk. Subgroup analysis by ethnicity also showed that associations are significant in Asian. Five prognosis studies were also included. Patients with TT genotype had a higher survival rate at 20-months-follow-up compared with those who carried TG or GG genotype (TT vs. TG+GG: OR=0.34, 95% CI: 0.12-0.99, P<0.05). CONCLUSIONS: MDM2 T309G polymorphism is associated with risk and prognosis of lung cancer. TT or T genotype may be associated with the reduced risk of lung cancer, especially in Asians. Meanwhile, TT genotype is also associated with the improved prognosis of the lung cancer.

[Positron emission tomography with special tracers in pulmonary abnormalities].

OBJECTIVE: To assess the value of positron emission tomography (PET) with (11)C-choline (CH), (11)C-methionine (MET), (18)F-fluorothymidine (FLT), and (11)C-acetate (AC) in diagnosis of pulmonary abnormalities and the features of pulmonary abnormalities in PET. METHODS: From June 2002 to June 2007, 100 patients with pulmonary nodules or masses confirmed by CT scans received PET with special tracers. Fifty-eight patients received CH-PET, 16 patients received MET-PET, 22 patients received FLT-PET, 4 patients received AC-PET. PET data was analyzed by visual method and semiquantitative method with standard uptake value (SUV). Diagnoses were compared with pathology and follow-up survey. RESULTS: For identification of pulmonary neoplasms with CH-PET, the sensitivity, specificity and accuracy were 84.2% (32/38), 57.9% (11/19) and 75.4% (43/57). In cancer cases, SUV had no correlation with tumor size or age. For identification of pulmonary neoplasms with MET-PET, the sensitivity, specificity and accuracy were 6/7, 6/9 and 75.0% (12/16). In cancer cases, SUV had not correlation with tumor size or age. For identification of pulmonary neoplasms with FLT-PET, the sensitivity, specificity and accuracy were 85.7% (12/14), 2/8 and 63.6% (14/22). In cancer cases, SUV had not correlation with tumor size or age. In AC-PET, only 1 case of pulmonary metastasis of kidney clear cell carcinoma showed acetate avid. Two squamous cell carcinoma and 1 adenocarcinoma didn't appear abnormal in AC-PET. CONCLUSION: CH, MET, FLT, AC are valuable in diagnosing but also lead to false positive and false negative.