Polyvinyl chloride microplastics induce changes in gene expression and organ histology along the HPG axis in Cyprinus carpio var. larvae.

The negative consequences of microplastics pollution on the health of aquatic species have garnered extensive attention. However, the mechanisms through which microplastics may cause harm in the reproductive processes of fish remain unknown. For this study, Cyprinus carpio var. was subjected to four treatments with various concentrations of PVC microplastics for 60 days, through food rationed diets (no plastic control, 10%, 20% and 30%). The gonadosomatic indices, gonad and brain histologies, sex hormone levels, and transcriptional and translational genes in the hypothalamic-pituitary-gonadal (HPG) axes of both sexes were observed. According to the results, the gonadosomatic indices were significantly decreased, gonadal development was delayed, and the level of estradiol (E2) in the females was significantly elevated. In addition, the expression levels of genes associated with the HPG axis in the brains and gonads (gnrh, gtha1, fshß, cyp19b, erα, vtg1, dmrt1, sox9b, and cyp19a) and the transcription levels of apoptosis-related genes in the brains and gonads (caspase3, bax, and bcl-2) exhibited significant changes. Further investigation revealed that the translation levels of genes linked to sex differentiation and sex steroid hormone (cyp19b and dmrt1) were significantly altered. These findings indicated that PVC likely microplastics may have a negative impact on the reproductive system of Cyprinus carpio var. by inhibiting gonadal development, affecting the gonad and brain structures, and altering the levels of steroid hormones and the expression of HPG axis-related genes. This work provides new insights into the toxicity of microplastics in aquatic organisms by revealing that PVC microplastics are a potential threat against the reproduction of fish populations.

Exposure of Cyprinus carpio var. larvae to PVC microplastics reveals significant immunological alterations and irreversible histological organ damage.

Microplastics have become pervasive in ambient aquatic ecosystems over the last decade and are currently a serious global scale concern. To evaluate the potential toxic effects of PVC (polyvinyl chloride) microplastics on the immune functions of freshwater fish, this study undertook a conducted chronic 60-day dietary exposure experiment with Cyprinus carpio var. larvae. We exposed the fish to four microplastic treatments of different concentrations (food rationed diets): no-plastic (control), 10%, 20% and 30%. At the end of the experimental period the impacts of microplastics on the histology, biochemistry, ROS (reactive oxygen species) levels and gene transcription of immune organs were investigated. The results revealed that PVC microplastics induced cytoplasmic vacuolation in the liver, damaged villi in the intestine, inflammatory cell infiltration, hemosiderosis and vacuolar degeneration in the spleen, glomeruli tuft shrinkage and aggregation of melanin macrophage cells in the kidney. Moreover, following PVC microplastics exposure, ROS levels in the liver and protein levels of pro-inflammatory cytokines including IL-6, IL-8, and TNFα in the liver and serum were increased. Furthermore, modifications in the activities of non-specific immunoenzyme ACP (Acid phosphatase), AKP (alkaline phosphatase), LZM (lysozyme), and expression levels of a range of immune-related genes were observed. Using various techniques at the histological, biochemical and molecular levels, our findings demonstrated the effects of PVC microplastics on changes and imbalances in the immune status of carp. The results of this study provide basic toxicological data toward elucidating and quantifying the impacts of microplastics immunotoxicity on aquatic organisms.

A detection panel of novel methylated DNA markers for malignant pleural effusion.

Background: Cytology remains the gold standard for the detection of malignant cells in pleural effusion. However, its sensitivity is limited. The aim of this study was to establish a novel panel of cancer-specific methylated genes for the differential diagnosis of malignant pleural effusion (MPE). Methods: A cohort of 100 cancer patients (68 lung cancer, 32 other malignant tumors) and 48 patients with benign disease presenting with pleural effusion was prospectively enrolled. Pleural effusion was evaluated by means of cytopathological investigation and DNA methylation of SHOX2, RASSF1A, SEPTIN9 and HOXA9 in the cellular fraction. DNA methylation in bisulfite-converted DNA was determined using quantitative methylation-specific real-time PCR (MS-PCR). Cytopathological and DNA methylation results were evaluated with regard to the final clinical diagnosis. Results: The LungMe® SHOX2 and RASSF1A Assay (Tellgen Corporation, China) has been reported to be highly sensitive and specific for lung cancer using bronchial aspirates. As expected, LungMe® detected metastases of lung cancer (sensitivity: 76.5%) as well as metastases of other malignant tumors (sensitivity: 68.8%). OncoMe, a novel combination of SHOX2, RASSF1A, SEPTIN9 and HOXA9 methylation, led to an additional 11% increase in the detection rate of MPE, resulting in a sensitivity of 85% and a specificity of 96%. Overall, OncoMe showed a higher positive detection rate in SCLC (100%), LUAC (87%), OC (100%), BC (92.9%), GC (80.0%), and MESO (80%) than in LUSC (50%). Cytopathological analyses only detected 23 positive samples, which were all positively measured by both LungMe® and OncoMe. Conclusion: OncoMe has potential for use as a biomarker for the detection of MPE, even not limited to lung cancer.

EFNA3 as a predictor of clinical prognosis and immune checkpoint therapy efficacy in patients with lung adenocarcinoma.

BACKGROUND: Ephrin receptors (Eph) and their ligands, called ephrins, function in various disease processes. However, the expression level and prognostic value of Eph/ephrins in lung adenocarcinoma (LUAD) are still unclear. METHODS: The Oncomine and GEPIA databases were used to explore the differential expression of Eph/ephrins in LUAD. Kaplan-Meier plotter was selected to explore the prognostic value of Eph/ephrins. The cBioPortal database was used to analyze the genetic variation of the EFNA3 gene. Immunohistochemistry was used to analyze the expression level and clinical value of ephrin-A3 protein in clinical LUAD tissue. Weighted coexpression network analysis (WGCNA) and gene set enrichment analysis (GSEA) identified the potential regulatory mechanism of EFNA3. CCK-8 assays and colony-forming experiments were used to investigate whether EFNA3 can regulate cell proliferation ability in LUAD. Analysis of lactate, ATP, and glucose uptake levels was used to explore the effect of EFNA3 on glycolysis ability. In addition, we investigated the relationship between EFNA3 and tumor infiltrating immune cells (TIICs). Finally, the potential immunotherapy response prediction value of EFNA3 was also explored. RESULTS: In this study, we found that EFNA3 expression was significantly correlated with both overall survival (OS) and progression-free survival (PFS) in LUAD patients based on a comprehensive analysis of the Eph/Ephrin family. Next, the expression of the EFNA3 protein was increased in LUAD tissues and was designated an independent prognostic risk factor. Mechanistically, EFNA3 may be involved in nuclear division, synaptic function, and ion channel activity-related pathways. In vitro experiments confirmed the role of EFNA3 in promoting LUAD cells and showed that it could regulate glycolytic capacity. Moreover, EFNA3 was negatively associated with immunity, stromal infiltration, and several TIICs. Finally, EFNA3 was found to be positively related to multiple immunotherapy biomarkers. CONCLUSIONS: In conclusion, increased EFNA3 in LUAD patients predicted worse clinical prognosis, promoted LUAD cell proliferation and glycolysis ability, and was related to immunotherapy response.

Ultrasound assessment of the rectus femoris in patients with chronic obstructive pulmonary disease predicts poor exercise tolerance: an exploratory study.

BACKGROUND: Reduced exercise tolerance is an important clinical feature of chronic obstructive pulmonary disease (COPD) and is associated with poor prognosis. The 6-min walk test (6MWT) is widely used to assess exercise capacity; however, it is not commonly administered in primary medical institutions because it requires a suitable site and professional training. Ultrasound has great potential for evaluating skeletal muscle dimensions in COPD. However, whether skeletal muscle ultrasound can predict impaired exercise tolerance is unclear. METHODS: The study included 154 stable patients with COPD, who were randomly divided into a development set and a validation set. The thickness (RFthick) and cross-sectional area (RFcsa) of the rectus femoris were measured using ultrasound. Standardized RFthick (STD- RFthick) and Standardized RFcsa (STD-RFcsa) were obtained via standardization of RFthick and RFcsa by patients' height. RESULTS: Strong correlations were observed between the 6MWD and RFthick (r = 0.84, p < 0.001) and between the 6MWD and RFcsa (r = 0.81, p < 0.001). In the development set, the optimal cut-off values for men and women for predicting poor exercise tolerance were < 3.098 cm/m and < 3.319 cm/m for STD-RFthick and < 4.052 cm2/m and < 4.366 cm2/m for STD-RFcsa, respectively. In the validation set, the area under the curve (AUC) values for the prediction of a 6MWD < 350 by STD-RFthick and STD-RFcsa were 0.881 and 0.903, respectively. Finally, the predictive efficacy of STD-RFthick (AUC: 0.922), STD-RFcsa (AUC: 0.904), and the derived nomogram model (AUC: 0.98) for exercise tolerance was superior to that of the sit-to-stand test and traditional clinical features. CONCLUSIONS: Rectus femoris ultrasound has potential clinical application to predict impaired exercise tolerance in patients with COPD.

Development and Validation of a Nomogram for Predicting the Disease Progression of Nonsevere Coronavirus Disease 2019.

BACKGROUND AND OBJECTIVES: The majority of coronavirus disease 2019 (COVID-19) cases are nonsevere, but severe cases have high mortality and need early detection and treatment. We aimed to develop a nomogram to predict the disease progression of nonsevere COVID-19 based on simple data that can be easily obtained even in primary medical institutions. METHODS: In this retrospective, multicenter cohort study, we extracted data from initial simple medical evaluations of 495 COVID-19 patients randomized (2:1) into a development cohort and a validation cohort. The progression of nonsevere COVID-19 was recorded as the primary outcome. We built a nomogram with the development cohort and tested its performance in the validation cohort. RESULTS: The nomogram was developed with the nine factors included in the final model. The area under the curve (AUC) of the nomogram scoring system for predicting the progression of nonsevere COVID-19 into severe COVID-19 was 0.875 and 0.821 in the development cohort and validation cohort, respectively. The nomogram achieved a good concordance index for predicting the progression of nonsevere COVID-19 cases in the development and validation cohorts (concordance index of 0.875 in the development cohort and 0.821 in the validation cohort) and had well-fitted calibration curves showing good agreement between the estimates and the actual endpoint events. CONCLUSIONS: The proposed nomogram built with a simplified index might help to predict the progression of nonsevere COVID-19; thus, COVID-19 with a high risk of disease progression could be identified in time, allowing an appropriate therapeutic choice according to the potential disease severity.

Ultrasonic Elastography of the Rectus Femoris, a Potential Tool to Predict Sarcopenia in Patients With Chronic Obstructive Pulmonary Disease.

Purpose: Skeletal muscle dysfunction is common in patients with chronic obstructive pulmonary disease (COPD) and is associated with a poor prognosis. Abnormal muscle quantity of the lower limbs is a manifestation of skeletal muscle dysfunction in patients with COPD. Shear wave ultrasound elastography (SWE) is a novel and possible tool to evaluate qualitative muscle parameters. This study explores the feasibility of SWE to measure the stiffness of the rectus femoris and evaluates its value in predicting sarcopenia in patients with COPD. Methods: Ultrasound examination of the rectus femoris was performed to determine the mean elasticity index (SWEmean), cross-sectional area (RFcsa), and thickness (RFthick) using grayscale ultrasonography (US) and SWE in 53 patients with COPD and 23 age-matched non-COPD healthy controls. The serum levels of circulating biomarkers (GDF15, resistin, and TNF-α) were measured using ELISA. The definition of sarcopenia followed the guidelines from the Asian Working Group for Sarcopenia. Receiver operating characteristic (ROC) curve analysis of the SWEmean, RFthick, and RFcsa was used to evaluate their predictive ability for sarcopenia. Results: The intraobserver and interobserver repeatability of SWE performance was excellent (all correlation coefficients > 0.95; p < 0.05). The SWEmean of the rectus femoris in patients with COPD (8.98 ± 3.12 kPa) was decreased compared with that in healthy controls (17.00 ± 5.14 kPa) and decreased with advanced global initiative for chronic obstructive lung disease (GOLD) stage. Furthermore, SWEmean was found to be independent of sex, height, and body mass, and a lower SWEmean in patients with COPD was positively associated with reduced pulmonary function, worse physical function, poor exercise tolerance, decreased muscle strength, and worse dyspnea index score. The correlation between physical function [five-repetition sit-to-stand test (5STST)], muscle function, and SWEmean was higher than those of RFthick and RFcsa. In addition, SWEmean was negatively correlated with serum GDF15 levels (r = -0.472, p < 0.001), serum resistin levels (r = -0.291, p = 0.035), and serum TNF-α levels (r = -0.433, p = 0.001). Finally, the predictive power of SWEmean [area under the curve (AUC): 0.863] in the diagnosis of sarcopenia was higher than that of RFthick (AUC: 0.802) and RFcsa (AUC: 0.816). Conclusion: Compared with grayscale US, SWE was not affected by the patient's height, weight, or BMI and better represented skeletal muscle function and physical function. Furthermore, SWE is a promising potential tool to predict sarcopenia in patients with COPD.

Malignant Transformation of a Borderline Ovarian Tumor With Pulmonary and Pleural Metastases After Years of Latency: A Case Report and Literature Review.

Borderline ovarian tumor (BOT) refers to a distinct tumor of the ovary of epithelial origin and typically has a favorable prognosis. However, these tumors are not exempt from risks of recurrence and malignant transformation, which can arise from the remaining ovarian tissue, peritoneal implants, or distant localization. Here, we report a case of a mucinous BOT with multiple pulmonary cystic nodules without evidence of pulmonary metastasis even after two fine needle biopsies. Staging surgery was performed, and no evidence of peritoneal implants or invasion to adjacent organs found. At the end of the 7-year monitored follow-up after surgery, the pulmonary lesions were found to be increased in size. The transbronchial lung biopsy and pleural biopsy confirmed transformation into malignant mucinous adenocarcinoma with pleural metastasis. In the current case, we observed potential pulmonary metastasis of the BOT with malignant transformation and a latency as long as 7 years, which reminds us that multiple pulmonary cystic changes in patients with BOTs should be screened carefully to evaluate the pulmonary involvement of BOTs and potentially false-negative results after fine needle biopsy. Thus, a thorough check-up for complete staging of the disease and a close long-term follow-up to monitor potential recurrence and malignant transformation are advised.

Large Tracheocutaneous Fistula Successfully Treated With Bronchoscopic Intervention and Flap Grafting: A Case Report and Literature Review.

Tracheocutaneous fistula (TCF) is the most common related post-operative complication after tracheotomy. Treatments such as surgery and flap grafting are usually applied to close TCFs. We report a case of a large TCF with an area of ~3.0 cm × 1.0 cm. Here, we describe a relatively convenient approach for the management of a patient with a large TCF. In our treatment strategy, a coverd tracheal stent was used to cover the defect by bronchoscopy, the bronchial defect was closed with a local turnover flap, the structure was reinforced with biodegradable material (RapidSorb Plate 2.0), and then transplantation of a deltopectoral flap was performed. It is worth noting that the patency of the trachea was maintained during the whole surgery course. No recurrence or complications occurred after the 12-month follow-up. The large TCF was successfully treated with bronchoscopic intervention, biodegradable material and flap grafting, and without cartilage grafting.

Acute mediastinitis associated with tracheobronchial tuberculosis and aspergillosis: a case report and literature review.

Acute mediastinitis (AM) is a rare but life-threatening disease. Here, we report a case of AM secondary to endobronchial tuberculosis (EBTB) and pseudomembranous Aspergillus tracheobronchitis (PMATB) co-infection. EBTB was confirmed by tissue culture for Mycobacterium tuberculosis and GeneXpert MTB/RIF (Cepheid, Sunnyvale, CA, USA) detection (simultaneous detection of M. tuberculosis and resistance to rifampin) using endobronchial biopsies; PMATB was confirmed by histopathology. Even with antibiotic treatment and systemic support treatment, the patient died of massive hemoptysis on day 10 after admission. When immunocompromised hosts have AM, especially with central airway involvement, EBTB and aspergillosis should be considered potential causes. Bronchoscopy is helpful for rapid diagnosis and administering precise treatment.

Endobronchial Valves for the Treatment of Bronchopleural Fistula and Pneumothorax Caused by Pulmonary Cryptococcosis in an AIDS Patient.

Cryptococcal disease is an opportunistic infection that occurs primarily among people with advanced HIV disease and is an important cause of morbidity and mortality. Spontaneous pneumothorax (SP) is rare in acquired immune deficiency syndrome (AIDS) patients with pulmonary cryptococcosis (PC), but when it occurs, rapid and effective treatment is crucial to the prognosis, with mortality rates varying from 30 to 60%. SP is related to pneumonia mainly due to bacterial infections and pneumocystic jirovecii pneumonia (PJP). However, SP caused by PC is rare. When it occurs, it is often fatal and refractory, which is a challenge both for patients and clinicians. Here, we report a case of SP during the treatment of cryptococcal disease in a patient with AIDS. The pneumothorax remained despite chest tube drainage and evolved into a bronchopleural fistula that was confirmed by the Chartis system. The pneumothorax was significantly resolved following the placement of 2 endobronchial valves (EBVs). The patient tolerated the procedure very well and the pneumothorax gradually resolved. When immunocompromised patients suffer from refractory pneumothorax or prolonged air leaks, EBV implantation may be a feasible and minimally invasive procedure for this vulnerable population.

Multiple extramedullary plasmacytomas of the trachea and pharyngeal tissue: a case report and literature review.

Extramedullary plasmacytoma (EMP) is an infrequent form of plasma cell dyscrasia that presents as a mass of monoclonal plasma cells located in extramedullary soft tissues with no skeletal component. EMP constitutes ~4% of all plasma cell neoplasms and occurs mostly in the upper respiratory tract. Here, we report a rare case of multiple EMPs involving the trachea, laryngopharynx, and oropharynx, which caused symptoms of airway obstruction as the only clinical manifestation. The patient was diagnosed by histopathology of the tissue from bronchoscopic resection and successfully managed with bronchoscopic intervention to treat lesions in the trachea and radiotherapy combined with surgical resection to treat lesions in the pharynx. There was no recurrence after 14 months of follow-up. Endoscopic intervention plays a key role in the rapid diagnosis and treatment of EMP involving the central airways.

Pathological and diagnostic implications of DCAF16 expression in human carcinomas including adenocarcinoma, squamous cell carcinoma, and urothelial carcinoma.

DCAF16 is a DDB1-CUL4 associated factor. The expression pattern of DCAF16 in human carcinomas is largely unknown. Here, we investigated DCAF16 expression in a series of human normal epithelial tissues and carcinomas using immunohistochemistry. DCAF16 expression was detected mainly in the cytoplasm in epithelial tissues including thyroid follicles (3/3), epithelium of the prostate glands (2/8), epithelium of the gastric glands (1/2), bronchial epithelium (1/1), epithelium of the intestine (1/1), and hepatocellular epithelium (3/5). There were only 2 cases showing strong immunostaining. Nuclear expression of DCAF16 was detected in a few human carcinomas (0.8%, 9/83). Cytoplasmic DCAF16 expression was detected in human carcinomas including adenocarcinoma (80.0%, 52/65), squamous cell carcinoma (30.8%, 4/13), and urothelial carcinoma (100%, 5/5). The total positive rate of DCAF16 expression was 73.5% (61/83), higher than that in normal tissues (45.8%, 11/24) (P < 0.05). The positive rate of DCAF16 expression in adenocarcinoma (80.0%, 52/65) was higher than that in squamous cell carcinoma (30.8%, 4/13) (P < 0.05). Interestingly, we found that DCAF16 expression in human carcinomas was significantly associated with a higher degree of differentiation (P < 0.05). Our results suggest that DCAF16 is expressed in various human carcinomas including adenocarcinoma, squamous cell carcinoma, and urothelial carcinoma and is not suitable to be used as a diagnostic marker for these cancers. In addition, DCAF16 expression in human carcinomas was elevated compared with that in normal epithelial tissues, suggesting its possible role in oncogenesis. However, the mechanism involved in elevation of DCAF16 expression and its function in human carcinoma needs to be further investigated.