Differences in Genomic Alterations and Accumulations of Heavy Metals Between Advanced Non-small Cell Lung Cancer Patients with and without Bone Metastasis.

Purpose: Bone metastasis (BoM) has been closely associated with increased morbidity and poor survival outcomes in patients with non-small cell lung cancer (NSCLC). Given its significant implications, this study aimed to systematically compare the biological characteristics between advanced NSCLC patients with and without BoM. Methods: In this study, the genomic alterations from the tumor tissue DNA of 42 advanced NSCLC patients without BoM and 67 patients with BoM and were analyzed by a next-generation sequencing (NGS) panel. The serum concentrations of 18 heavy metals were detected by inductively coupled plasma emission spectrometry (ICP-MS). Results: A total of 157 somatic mutations across 18 mutated genes and 105 somatic mutations spanning 16 mutant genes were identified in 61 out of 67 (91.05%) patients with BoM and 37 of 42 (88.10%) patients without BoM, respectively. Among these mutated genes, NTRK1, FGFR1, ERBB4, NTRK3, and FGFR2 stood out exclusively in patients with BoM, whereas BRAF, GNAS, and AKT1 manifested solely in those without BoM. Moreover, both co-occurring sets of genes and mutually exclusive sets of genes in patients with BoM were different from those in patients without BoM. In addition, the serum concentrations of Cu and Sr in patients with BoM were significantly higher than in patients without BoM. One of our aims was to explore how these heavy metals associated with BoM interacted with other heavy metals, and significant positive correlations were observed between Cu and Co, between Cu and Cr, between Sr and Ba, and between Sr and Ni in patients with BoM. Given the significant impacts of molecular characteristics on patients' prognosis, we also observed a noteworthy negative correlation between EGFR mutations and Co, alongside a significant positive correlation between TP53 mutations and Cd. Conclusions: The genomic alterations, somatic interactions, key signaling pathways, functional biological information, and accumulations of serum heavy metals were markedly different between advanced NSCLC patients with and without BoM, and certain heavy metals (e.g., Cu, Sr) might have potentials to identify high-risk patients with BoM.

Bilateral Multiple Fractures Obstruct Quantitation of 99m Tc-Pyrophosphate Imaging for Cardiac Amyloidosis.

ABSTRACT: A 57-year-old woman who had persistent symptoms of transthyretin cardiac amyloidosis underwent 99m Tc-pyrophosphate ( 99m Tc-PYP) scintigraphy. The 99m Tc-PYP planar and SPECT/CT fusion image showed diffuse myocardial uptake and multiple fractures of the sternum and ribs. These fractures interfered with semiquantitative scores of 99m Tc-PYP uptake, leading to false positive in 99m Tc-PYP imaging.

Establishment and Clinical Application of the General Comfort Scale for Postoperative Lung Cancer Patients.

Background and purpose The concept of enhanced recovery after surgery (ERAS) not only reflects rapid perioperative recovery but also focuses on the comfort experience of inpatients. This study intends to establish a clinically applicable general comfort questionnaire (GCQ) for patients with lung cancer after surgery and verify its clinical application effect. Methods The comfort index items for postoperative lung cancer were formed by combining previous research and literature, clinically applied comfort scales, and expert interviews. The Delphi method was used to conduct two rounds of expert consultations to determine the final index and establish a postoperative comfort scale for lung cancer patients. This scale was used to conduct a questionnaire survey on 200 patients to test the reliability and validity of the scale. Results The comfort scale contains 3 dimensions and 10 items and is easy to operate and evaluate in clinical applications. The Cronbach's α coefficient of the comfort scale is 0.801, and the scale content validity index (SCVI/ave) is 0.97. The common factor 1 and 2 characteristic roots of scale structural validity evaluation are 3.257 and 1.352 respectively, both greater than 1, with cumulative variance contribution rates of 32.57% and 13.52%. Pain and getting out of bed are the main factors influencing patient comfort. Conclusion The postoperative comfort scale for lung cancer patients has high clinical application reliability and validity. This study identified pain and mobility (early ambulation or getting out of bed) as the primary factors influencing the postoperative comfort of lung cancer patients.

An Analysis of Public Perception and Concern Toward Electronic Cigarettes: Exploring Attitudes and Profiles.

Introduction The emergence of electronic cigarettes (e-cigarettes) poses a new challenge to tobacco control efforts. With their increasing popularity, particularly among youth, public concerns have been raised in Mainland China. Further investigation is necessary to fully understand the safety and potential adverse effects of e-cigarettes. Methods The Baidu search index (BSI) was employed using e-cigarette related terms from January 1, 2011, to April 4, 2022. The search volume for each term was recorded and analyzed for the search trend module, geodemographic module, search-demand module, regional preferences, demographic preferences, and user demand. Results According to our analysis, the total BSI for the 18 e-cigarette related search keywords was 39,027,819. The average annual percentage change of BSI indicated an upward trend for each of these categories, including health issues (p < 0.05), definition (p < 0.05), product and promotions (p < 0.05), and policy and regulations. Of all inquiries, 59.38% originated from females and 40.62% from males. The total valid BSI for e-cigarette related words was 165,076,588, and 11.59% of all search inquiries were from individuals aged 19 years and younger. Our analysis also revealed that the public's primary concerns regarding e-cigarettes were related to their quality and potential health issues. Conclusions E-cigarettes enjoy great popularity nationwide, but product quality and safety are major public concerns. Regulation of e-cigarettes for their standard production, quality control, advertisement, and target customers should be implemented promptly, and the public needs to have a clear perception of e-cigarettes, especially adolescents. E-cigarette related health damages or consequences require further investigation, and advertisements and promotions for e-cigarettes should be strictly controlled by the government.

Multigene testing panels reveal pathogenic variants in sporadic breast cancer patients in northern China.

Background: Breast cancer, the most prevalent malignancy in women worldwide, presents diverse onset patterns and genetic backgrounds. This study aims to examine the genetic landscape and clinical implications of rare mutations in Chinese breast cancer patients. Methods: Clinical data from 253 patients, including sporadic and familial cases, were analyzed. Comprehensive genomic profiling was performed, categorizing identified rare variants according to the American College of Medical Genetics (ACMG) guidelines. In silico protein modeling was used to analyze potentially pathogenic variants' impact on protein structure and function. Results: We detected 421 rare variants across patients. The most frequently mutated genes were ALK (22.2%), BARD1 (15.6%), and BRCA2 (15.0%). ACMG classification identified 7% of patients harboring Pathogenic/Likely Pathogenic (P/LP) variants, with one case displaying a pathogenic BRCA1 mutation linked to triple-negative breast cancer (TNBC). Also identified were two pathogenic MUTYH variants, previously associated with colon cancer but increasingly implicated in breast cancer. Variants of uncertain significance (VUS) were identified in 112 patients, with PTEN c.C804A showing the highest frequency. The role of these variants in sporadic breast cancer oncogenesis was suggested. In-depth exploration of previously unreported variants led to the identification of three potential pathogenic variants: ATM c.C8573T, MSH3 c.A2723T, and CDKN1C c.C221T. Their predicted impact on protein structure and stability suggests a functional role in cancer development. Conclusion: This study reveals a comprehensive overview of the genetic variants landscape in Chinese breast cancer patients, highlighting the prevalence and potential implications of rare variants. We emphasize the value of comprehensive genomic profiling in breast cancer management and the necessity of continuous research into understanding the functional impacts of these variants.

17ß-Estradiol Mediates Staphylococcus aureus Adhesion in Vaginal Epithelial Cells via Estrogen Receptor α-Associated Signaling Pathway.

Staphylococcus aureus, a major opportunistic pathogen in aerobic vaginitis (AV), can potentially invade the host and occasionally cause infections. Estrogen is associated with an altered immune response of vaginal epithelial cells and prevention of certain vaginal infectious diseases. However, the molecular mechanisms involving estrogen and S. aureus adhesion to vaginal epithelial cells remain unclear. Thus, here, VK2/E6E7 vaginal epithelial cells were infected with S. aureus, and the role of the estrogen receptor α-associated signaling pathway (ERα/FAK/Src/iNOS axis) in S. aureus adhesion was evaluated. The estrogen-associated phosphorylation status of ERα, FAK, and Src and the protein level of iNOS were assessed by western blotting. We used a specific ERα inhibitor to validate the involvement of the ERα-associated signaling pathway. The results showed that with exposure to 1 nM estrogen for 24 h, transient ERα-associated pathway activation was observed, and the protein expression upregulation was accompanied by a dose-dependent increase in 17-ß-estradiol (E2) content and increased S. aureus adherence to vaginal epithelial cells. Estrogen-induced activation of the ERα/FAK/Src/iNOS axis was notably inhibited by the specific ERα inhibitor (ICI 182780). Simultaneously, a significant decrease in the number of adherent S. aureus was observed. However, this inhibitory effect diminished after inhibitor treatment for 24 h. Our findings suggested that the ERα-associated signaling pathway might be involved in S. aureus adherence to vaginal epithelial cells, which appeared to be linked to enhanced cell adhesion leading to AV.

Differences of genomic alterations and heavy metals in non-small cell lung cancer with different histological subtypes.

PURPOSE: This study aimed to explore the correlations among heavy metals concentration, histologic subtypes and molecular characteristics in patients with non-small cell lung cancer (NSCLC). METHODS: In this study, an NGS panel of 82 tumor-associated genes was used to identify genomic alternations in 180 newly diagnosed patients with NSCLC. The concentrations of 18 heavy metals in the serum samples were detected by inductively coupled plasma emission spectrometry (ICP-MS). RESULTS: A total of 243 somatic mutations of 25 mutant genes were identified in 115 of 148 patients with LUAD and 45 somatic mutations of 15 mutant genes were found in 24 of 32 patients with LUSC. The genomic alternations, somatic interactions, traditional serum biomarkers, and heavy metals were markedly different between patients with LUAD and LUSC. Moreover, patients with LUSC were significantly positively correlated with Ba, but not LUAD. Lastly, patients with EGFR mutations presented significant negative correlations with Cd and Sr, whereas patients with TP53 mutations showed a significant positive correlation with Pb. CONCLUSION: The genomic alternations, somatic interactions, traditional serum biomarkers, and heavy metals were different between patients with LUAC and LUSC, and heavy metals (e.g., Ba, Pb, and Cd) may contribute to the tumorigenesis of NSCLC with different histological and molecular subtypes.

Differences in actionable genomic alterations between brain metastases and non­brain metastases in patients with non­small cell lung cancer.

Brain metastases (BM) have been closely associated with increased morbidity and poor survival outcomes in patients with non­small cell lung cancer (NSCLC). Excluding risk factors in histological subtypes, genomic alterations, including epidermal growth factor receptor mutations and anaplastic lymphoma kinase (ALK) rearrangements have been also regarded as greater risk factors for BM in the aspect of molecular subtypes. In the present study, 69 tumor tissues and 51 peripheral blood samples from patients with NSCLC were analyzed using a hybridization capture­based next­generation sequencing (NGS) panel, including 95 known cancer genes. Among the 90 patients with stage IV NSCLC, 26 cases suffered from BM and 64 cases did not. In total, 174 somatic mutations in 35 mutated genes were identified, and 12 of these genes were concurrently present in the BM group and the non­BM group. Importantly, five mutated genes including ALK, cytidine deaminase (CDA), SMAD family member 4 (SMAD4), superoxide dismutase 2 (SOD2) and Von Hippel­Lindau tumor suppressor (VHL) genes were uniquely detected in the BM group, and they were enriched in the Hippo signaling pathway, pyrimidine metabolism and pantothenate and co­enzyme A (CoA) biosynthesis, as demonstrated using Kyoto Encyclopedia of Genes and Genomes enrichment analysis. RNA polymerase II transcription regulator complex and promyelocytic leukemia nuclear body were the top functional categories according to the Gene Ontology enrichment analysis in the BM group and non­BM group, respectively. Furthermore, 43.33% (13/30) of mutated genes were detected by both tumor tissue deoxyribonucleic acid (DNA) and plasma­derived circulating tumor DNA (ctDNA) in the non­BM group, while this percentage was only limited to 29.41% (5/17) in the BM group. To summarize, significant differences in somatic mutations, somatic interactions, key signaling pathways, functional biological information, and clinical actionability for the therapy of targeted agents were founded between the BM group and the non­BM group, and ctDNA analysis may by applied as a more credible alternative for genomic profiling in patients with advanced NSCLC without BM, due to its higher consistency for genomic profiling between ctDNA analysis and tissue DNA analysis.

Diagnostic pitfall in a large cell lung cancer with testicular metastasis synchronous malignant pleural mesothelioma patient: A case report.

Large cell lung cancer metastases to the testis are scarce, although it is the most common malignancy and the most common site of metastases for breast, colorectal and kidney cancers. We hereby report a 28-year-old male patient admitted to our hospital with a chief complaint of scrotal enlargement, accompanied by chest pain and progressive dyspnea. The definite diagnosis was malignant pleural mesothelioma with the synchronous occurrence of large cell lung cancer with testicular metastasis. Sophisticated clinical manifestation of symptoms led to a time-consuming diagnosis, while the patient's condition deteriorated rapidly. Herein, we present this case to share our hard-learnt experience to increase clinician awareness and contribute to the information in the literature.

An Unusual False-Positive Uptake of Radioiodine Caused by Breast Implants.

ABSTRACT: A 40-year-old woman with a history of papillary thyroid cancer underwent ablative 131I therapy. Postablation whole-body 131I scintigraphy revealed not only increased activity in the thyroid bed but also in the anterior part of the chest. SPECT/CT images localized the activity in the bilateral breast implants.

Intravenous Tumor Thrombus From Papillary Carcinoma of Thyroid Demonstrated by 18F-FDG PET/CT.

ABSTRACT: A 24-year-old man with papillary thyroid carcinoma underwent 131I ablation after thyroidectomy. On posttherapy whole-body scintigraphy, only the remnant thyroid was visualized. In view of elevated unstimulated thyroglobulin level 7 months after 131I ablation, 18F-FDG PET/CT scan was ordered for further evaluation. On PET/CT images, a large filling defect from the dilated left brachiocephalic vein to superior vena cava was noted corresponding with high FDG uptake. It was considered as a malignant thrombus.

Prognostic value of post-ablation stimulated thyroglobulin in differentiated thyroid cancer patients with biochemical incomplete response: a bi-center observational study.

OBJECTIVE: Little is known regarding parameters predicting persistence/recurrence for differentiated thyroid cancer (DTC) patients exhibiting biochemical incomplete response (BIR) to initial therapy. High post-ablation stimulated thyroglobulin (ps-Tg) levels have undetermined prognostic significance in DTC patients with BIR. The goal of this bi-center study was to systemically assess the prognosis of DTC patients with BIR in relation to ps-Tg levels and to establish the determinants of clinical outcomes. DESIGN AND METHODS: The retrospective study of consecutive 81 DTC patients from two tertiary centers who were classified as BIR after total thyroidectomy and radioiodine ablation between January 2010 to December 2019 were analyzed. BIR was defined as ps-Tg > 10 ng/mL measured under thyroid hormone withdrawal at 9-12 months followed by radioiodine ablation, negative anti-Tg antibodies, and no structural evidence of disease. Multivariable regression models were used to evaluate potential risk factors associated with clinical outcomes. RESULTS: With a median follow-up of 5.4 years, 28 patients (34.6%) showed no evidence of disease and 50 patients (61.7%) were of a biochemical persistent status at the time of final follow-up. Conversely, 3 patients (3.7%) developed structural evidence of disease. Ps-Tg of 20.2 ng/mL or greater displayed the high positive predictive value (81%) for disease persistence/recurrence. Multivariate analysis revealed that only a high ps-Tg level (>20.2 ng/mL) was an independent risk factor for persistent/recurrent disease (odds ratio = 5.6; p < 0.001). CONCLUSION: The ps-Tg (>20.2 ng/mL) was a valuable predictor of disease persistence/recurrence in DTC patients with BIR.

Is thyroid hormone supplementation avoidable for patients with low-risk papillary thyroid cancer after thyroid lobectomy? A two-center observational study.

OBJECTIVE: Changing insights regarding the extent of surgery for low-risk papillary thyroid cancer (PTC) stir up discussions on the benefits and harms of thyroid lobectomy versus total thyroidectomy. The chance of needing postoperative thyroid hormone supplementation after thyroid lobectomy is still unclear. The purpose of this retrospective two-center study was to identify the incidence and risk factors of postoperative thyroid-stimulating hormone (TSH) elevation (>2.0 µIU/ml) after thyroid lobectomy for low-risk PTC. DESIGN AND METHODS: Medical records of 201 consecutive patients with low-risk PTC from two tertiary centers who underwent thyroid lobectomy between 2015 and 2019 were retrospectively reviewed. Postoperative thyroid function tests were measured regularly and patients were prescribed levothyroxine if the TSH level was higher than 2.0 µIU/ml. Multivariable regression models were used to evaluate potential risk factors associated with postoperative TSH elevation after thyroid lobectomy. RESULTS: At 6 weeks postoperatively, 85% had TSH level of >2 µIU/ml; this increased to 88% by 3-6 months. Receiver operating characteristic analysis identified preoperative TSH cut-off (>1.7 µIU/ml) to predict postoperative TSH elevation. Multivariate analysis revealed that only a high preoperative TSH level (>1.7 µIU/ml) was an independent risk factor for a postoperative TSH level of >2 µIU/ml (odds ratio = 7.71; p < .001). CONCLUSION: Nearly 90% of the patients who underwent thyroid lobectomy for low-risk PTC had a postoperative TSH level of >2 µIU/ml, necessitating thyroid hormone supplementation in accordance with current guidelines. This finding highlights that preoperative patient counseling should also focus on raising awareness about postoperative thyroid hormone supplementation for low-risk PTC patients seeking thyroid lobectomy.

An Unusual False-Positive Uptake of Radioiodine Caused by Posttraumatic Superficial Scab.

ABSTRACT: A 22-year-old man with a history of recurrent papillary thyroid cancer underwent 131I therapy. Posttherapeutic whole-body scintigraphy was performed 5 days after administration of 5.5 GBq of 131I. The scintigraphy revealed increased activity in the left elbow. On physical examination, the patient had posttraumatic superficial scab at the site of the abnormal activity.

Automatic identification of suspicious bone metastatic lesions in bone scintigraphy using convolutional neural network.

BACKGROUND: We aimed to construct an artificial intelligence (AI) guided identification of suspicious bone metastatic lesions from the whole-body bone scintigraphy (WBS) images by convolutional neural networks (CNNs). METHODS: We retrospectively collected the 99mTc-MDP WBS images with confirmed bone lesions from 3352 patients with malignancy. 14,972 bone lesions were delineated manually by physicians and annotated as benign and malignant. The lesion-based differentiating performance of the proposed network was evaluated by fivefold cross validation, and compared with the other three popular CNN architectures for medical imaging. The average sensitivity, specificity, accuracy and the area under receiver operating characteristic curve (AUC) were calculated. To delve the outcomes of this study, we conducted subgroup analyses, including lesion burden number and tumor type for the classifying ability of the CNN. RESULTS: In the fivefold cross validation, our proposed network reached the best average accuracy (81.23%) in identifying suspicious bone lesions compared with InceptionV3 (80.61%), VGG16 (81.13%) and DenseNet169 (76.71%). Additionally, the CNN model's lesion-based average sensitivity and specificity were 81.30% and 81.14%, respectively. Based on the lesion burden numbers of each image, the area under the receiver operating characteristic curve (AUC) was 0.847 in the few group (lesion number n ≤ 3), 0.838 in the medium group (n = 4-6), and 0.862 in the extensive group (n > 6). For the three major primary tumor types, the CNN-based lesion identifying AUC value was 0.870 for lung cancer, 0.900 for prostate cancer, and 0.899 for breast cancer. CONCLUSION: The CNN model suggests potential in identifying suspicious benign and malignant bone lesions from whole-body bone scintigraphic images.

Pivotal role of video-assisted thoracoscopic surgery in improving survival outcome of stage I non-small cell lung cancer in day surgery patients.

BACKGROUND: Lung cancer, the leading cause of cancer-related deaths worldwide, has high morbidity rates. Video-assisted thoracoscopic surgery (VATS) as day surgery makes surgical treatment ideally in time with the same quality of medical care. This study aimed to assess the safety of stage I NSCLC patients who underwent VATS at a day surgery center. METHODS: We retrospectively analyzed the clinical characteristics and tumor features of VATS patients at a single center, West China Hospital, from June 1, 2019, to December 31, 2020. Patients fulfilled all inclusion criteria, did not meet any exclusion criteria and underwent wedge resection, segmentectomy, or lobectomy with systematic lymph node dissection. RESULTS: The median patient age was 43 (range, 19-67) years. Of the 209 patients, most were women. A total of 108 (51.7%) patients underwent segmentectomy, 87 (41.6%) lobectomy, and 14 (6.7%) wedge resection with systematic lymph node dissection. According to the AJCC/UICC eighth edition of lung cancer stage grouping, stages IA, IA1, IA2, and IA3 were 195 (93.3%), 122 (58.4%), 50 (23.9%), and one (0.5%), respectively. A total of 36 (17.2%) patients were stage 0. Adenocarcinoma was predominantly the postoperative pathological diagnosis, as only 14 (6.7%) were benign. A total of 201 (96.17%) patients were discharged without a chest tube. The most common chief complaints were cough, incisional pain, and shortness of breath. No severe complications or life-threatening emergencies were observed. CONCLUSIONS: The day surgery mode of VATS for stage I NSCLC is safe and feasible, which makes surgical treatment ideally in time for stage I NSCLC patients with the same quality of medical care.

The Role of 17ß-Estrogen in Escherichia coli Adhesion on Human Vaginal Epithelial Cells via FAK Phosphorylation.

Estrogen, the predominant sex hormone, has been found to be related to the occurrence of vaginal infectious diseases. However, its role in the occurrence and development of bacterial vaginitis caused by Escherichia coli is still unclear. The objective of this study was to investigate the role of 17ß-estrogen in E. coli adhesion on human vaginal epithelial cells. The vaginal epithelial cell line VK2/E6E7 was used to study the molecular events induced by estrogen between E. coli and cells. An adhesion study was performed to evaluate the involvement of the estrogen-dependent focal adhesion kinase (FAK) activation with cell adhesion. The phosphorylation status of FAK and estrogen receptor α (ERα) upon estrogen challenge was assessed by Western blotting. Specific inhibitors for ERα were used to validate the involvement of ERα-FAK signaling cascade. The results showed that, following stimulation with 1,000 nM estrogen for 48 h, transient activation of ERα and FAK was observed, as was an increased average number of E. coli cells adhering to vaginal epithelial cells. In addition, estrogen-induced activation of ERα and FAK was inhibited by the specific inhibitor of ERα, especially when the inhibitor reached a 10 µM concentration and acted for 1 h, and a decrease in the number of adherent E. coli cells was observed simultaneously. However, this inhibitory effect diminished as the concentration of estrogen increased. In conclusion, FAK and ERα signaling cascades were associated with the increasing E. coli adherence to vaginal epithelial cells, which was promoted by a certain concentration of estrogen.

The Landscape of Genetic Alterations Stratified Prognosis in Oriental Pancreatic Cancer Patients.

BACKGROUND: Pancreatic cancer is a life-threatening malignant disease with significant diversity among geographic regions and races leading to distinct carcinogenesis and prognosis. Previous studies mainly focused on Western patients, while the genomic landscape of Oriental patients, especially Chinese, remained less investigated. METHODS: A total of 408 pancreatic cancer patients were enrolled. A panel containing 436 cancer-related genes was used to detect genetic alterations in tumor samples. RESULTS: We profiled the genomic alteration landscape of pancreatic duct adenocarcinoma (PDAC), intraductal papillary mucinous neoplasm (IPMN), periampullary carcinoma (PVC), and solid-pseudopapillary tumor (SPT). Comparison with a public database revealed specific gene mutations in Oriental PDAC patients including higher mutation rates of DNA damage repair-related genes. Analysis of mutational signatures showed potential heterogenous carcinogenic factors caused by diabetes mellitus. KRAS mutation, especially KRAS G12D mutation, was associated with poor survival, while patients not harboring the 17 significant copy number variations (CNVs) had a better prognosis. We further identified multiple correlations between clinicopathologic variables and genetic mutations, as well as CNVs. Finally, by network-based stratification, three classes of PDAC patients were robustly clustered. Among these, class 1 (characterized by the Fanconi anemia pathway) achieved the best outcome, while class 2 (involved in the platinum drug resistance pathway) suffered from the worst prognosis. CONCLUSIONS: In this study, we reported for the first time the genetic alteration landscape of Oriental PDAC patients identifying many Oriental-specific alterations. The relationship between genetic alterations and clinicopathological factors as well as prognosis demonstrated important genomic impact on tumor biology. This study will help to optimize clinical treatment of Oriental PDAC patients and improve their survival.