Efficacy and safety of modified endoscopic submucosal tunnel dissection for superficial esophageal circumferential lesions.

To evaluate the efficacy and safety of intra-tunnel dissection using hemostatic forceps and needle-type device for patients with esophageal circumferential lesions (ECLs). Patients with ECLs were enrolled in the study and underwent endoscopic submucosal tunnel dissection (ESTD) or hemostatic forceps-based ESTD (ESFTD). All patients were divided into three subgroups according to longitudinal length of the lesions (LLLs): >8 cm, 4-8 cm and < 4 cm. The clinical data such as gender, age, length of lesions and operating time were collected. A total of 152 patients were included in this study and comprised 80 cases of ESFTD and 72 cases of ESTD. The procedure time was markedly shorter in the ESFTD group than in the ESTD group (P < 0.001). Moreover, ESFTD significantly increased the rate of complete resection and reduced specimen injury in LLLs >8 cm and 4-8 cm subgroup compared with ESTD (P < 0.001), but not in <4 cm subgroup (P > 0.05). The perforation and infection rate were similar in ESFTD and ESTD group (P > 0.05). However, ESFTD effectively decreased the muscular injury rate' the duration of chest pain and the time from endoscopic surgery to first occurrence of esophageal stenosis compared with ESTD group (P < 0.01). ESFTD has better efficacy and safety than ESTD in the treatment of ECLs, especially for large lesions. ESFTD could be recommended for patients with ECLs.

FOXA2 promotes esophageal cancer migration and metastasis by activating CXCR4 expression.

Esophageal cancer is one of the most common malignant tumors worldwide and half of the patients present tumor metastasis at initial diagnosis. CXCR4 has been reported to be upregulated in esophageal cancer tissues and associated with tumor metastasis. However, the upstream transcriptional regulator of CXCR4 in esophageal cancer is still unclear. In this study, we found that transcription factor FOXA2 directly bound on the CXCR4 promoter region and activated its expression in esophageal cancer cells. The expression of FOXA2 was upregulated in esophageal cancer tissues and positively correlated with CXCR4. Moreover, knockout of FOXA2 significantly inhibited esophageal cancer migration and metastasis, which can be rescued by ectopically expressed CXCR4. Taken together, we reveal a novel transcriptional activator of CXCR4 in esophageal cancer, which might provide new strategies for esophageal cancer treatment.

The Applicability of ADA, AFU, and LAC in the Early Diagnosis and Disease Risk Assessment of Hepatitis B-Associated Liver Cirrhosis and Hepatocellular Carcinoma.

Objective: This study aimed to evaluate the applicability of adenosine deaminase (ADA), α-l-fucosidase (AFU), lactic acid (LAC), and their combined detection in the early diagnosis of chronic hepatitis B (CHB), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). Methods: A retrospective analysis of hepatitis B-positive liver disease patients admitted between 2015 and 2020 was conducted. The receiver operating characteristic (ROC) curve was used to determine the diagnostic value of each indicator in LC and HCC, and binary logistic regression analysis was performed to determine the factors and risks related to the occurrence of the two conditions. Results: The levels of ADA, AFU, and LAC were significantly increased in patients with CHB, LC, and HCC (p < 0.05). The ROC curve showed that the sensitivity and specificity of ADA, AFU, LAC, and their combined detection in the CHB and LC groups as well as in the LC and HCC groups reflected different degrees of clinical value. In the CHB and LC groups, the adjusted odds ratio (OR) values of ADA, AFU, and LAC among patients in the high-level group were 3.218, 1.859, and 11.474, respectively, when the median was considered the cutoff point. When quartiles were considered the cutoff point, the OR risk values of the adjusted levels of ADA, AFU, and LAC were higher than those of the lowest-level group (Q1) (p < 0.05). In the LC and HCC groups, the adjusted OR values of ADA, AFU, and LAC among patients in the high-level group were 0.967, 2.365, and 38.368, respectively. When quartiles were considered the cutoff point, the OR risk values of AFU and LAC levels were higher than those of the lowest-level group (Q1) (p < 0.05). Conclusion: ADA, AFU, and LAC demonstrated good value in the early diagnosis of LC and HCC. The combined detection of ADA+AFU+LAC is more effective than single detection for the early diagnosis of the two conditions. ADA, AFU, and LAC can serve as risk predictors of LC, while AFU and LAC can be considered early risk predictors of HCC.

Serum Albumin Levels are a Predictor of COVID-19 Patient Prognosis: Evidence from a Single Cohort in Chongqing, China.

BACKGROUND: COVID-19 infections are still at pandemic levels globally and there are currently no specific drugs to treat these infections. Previous studies have demonstrated that serum albumin levels were abnormally low in COVID-19 patients and might be used as a prognosis biomarker. Supplemental albumin has been used as an experimental therapeutic method. However, dynamic evaluation of albumin in patients with COVID-19 was limited and whether serum albumin could predict the prognosis of these patients is unknown. METHODS: We enrolled 79 COVID-19 patients in the present study and reviewed electronic medical laboratory records. Data was processed using SPSS software (Version 20.0) and correlation analysis was performed between serum albumin and other clinical and laboratory findings. RESULTS: Serum albumin levels were gradually decreased both in severe and non-severe COVID-19 patients. Moreover, 17.7% of the patients presented with hypoalbuminemia at least one time during 3 consecutive weekly time points. The hypoalbuminemia group displayed more severe disease and comorbidity that included fever, fatigue, headache, and dizziness on admission. Moreover, serum albumin levels were positively correlated with lymphocyte and RBC numbers, Hb and prealbumin levels as well as with total T cell numbers and the presence of CD4+ and CD8+ T cells. In contrast, there was a negative correlation with C-reactive protein levels and this was an indicator of patient recovery. CONCLUSION: Our results demonstrated that hypoalbuminemia was common in COVID-19 patients and its levels were linked to disease severity. Patients with fever, fatigue and headache or dizziness on admission were more likely to experience hypoalbuminemia. Dynamic monitoring of serum albumin is therefore necessary and should be performed during COVID-19 patient treatments as a tool for evaluating the prognosis of COVID-19 infections.

miR-9 alleviated the inflammatory response and apoptosis in caerulein-induced acute pancreatitis by regulating FGF10 and the NF-κB signaling pathway.

MicroRNAs (miRs) have been implicated in the development of acute pancreatitis (AP). However, the role and potential mechanism of miR-9 in AP progression remains unclear. Caerulein-treated AR42J cells were used as a cellular model of AP. Results revealed caerulein triggered an inflammatory response by promoting the secretion of inflammatory cytokines [tumor necrosis factor-α, interleukin (IL) 1ß and IL-6], as evidenced by ELISA. Furthermore, caerulein-induced apoptosis was reported by flow cytometry and western blot assays. Additionally, miR-9 expression was downregulated by caerulein treatment, as demonstrated by reverse transcription quantitative PCR. However, miR-9 overexpression reduced the inflammatory response and apoptosis in caerulein-treated AR42J cells. miR-9 knockdown resulted in opposite effects. Furthermore, fibroblast growth factor (FGF) 10 was validated to be targeted via miR-9 by luciferase, RNA immunoprecipitation and RNA pull-down assays. Results demonstrated increased FGF10 expression in caerulein-treated AR42J cells and that FGF10 overexpression exacerbated the caerulein-induced inflammatory response and apoptosis, while its knockdown had the opposite effect. Additionally, FGF10 reversed the effect of miR-9 on caerulein-induced injury in AR42J cells. Results demonstrated that miR-9 inhibited the expression of the nuclear factor κB (NF-κB) pathway-related proteins by downregulating FGF10. As a result, miR-9 decreased inflammatory response and apoptosis in caerulein-treated AR42J cells by targeting FGF10 and blocking NF-κB signaling, suggesting that miR-9 may serve as a novel target for AP treatment.

Antibody responses to SARS-CoV-2 in patients with COVID-19.

We report acute antibody responses to SARS-CoV-2 in 285 patients with COVID-19. Within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G (IgG). Seroconversion for IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. Serological testing may be helpful for the diagnosis of suspected patients with negative RT-PCR results and for the identification of asymptomatic infections.

G-Protein-Coupled Receptor 5 (LGR5) Overexpression Activates ß-Catenin Signaling in Breast Cancer Cells via Protein Kinase A.

BACKGROUND Targeting cancer stem cells (CSCs) in breast cancer (BrCa) may improve treatment outcome and patient prognosis. Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is a well-recognized adult stem cell and CRC marker, and previous reports have suggested the cancer-promoting role of LGR5 in breast cancer, but the mechanism remains unclear. MATERIAL AND METHODS Potential LGR5-associating genes were explored using STRING database, and LGR5 overexpression and knockdown was constructed in MCF-7 and MDA-MB-453 human BrCa cells, respectively. PKA catalytic subunit activation and PKA kinase activity in human BrCa cells was examined by Western blot and PKA kinase activity assay, respectively. Protein expression level or activation of ß-catenin and GSK-3ß in human BrCa cells was investigated by Western blot. Cell proliferation, colony formation, Transwell migration, cisplatin sensitivity, and in vivo tumor formation of human BrCa cells were examined. RESULTS LGR5 overexpression increased PKA activation and its kinase activity in human BrCa cells, which was decreased by LGR5 knockdown. LGR5 expression level or PKA kinase activity were correlated with ß-catenin Ser 552 phosphorylation but inversely correlated with GSK-3ß Ser9 phosphorylation in human BrCa cells in vitro. LGR5/PKA increased cell proliferation, colony formation, Transwell migration, and cisplatin resistance in vitro, as well as tumor formation in vivo, of human BrCa cells. CONCLUSIONS LGR5 activates the Wnt/ß-catenin signaling pathway in human BrCa cells in vitro via PKA.

Quantification of serum SOX2 DNA with FQ-PCR potentially provides a diagnostic biomarker for lung cancer.

Sex-determining region Y-box 2 (SOX2), as a subunit of transcription and reprogramming factor, plays a critical role in the development and progression of many malignancies, including lung cancer through gene amplification. In the present study, we aimed to quantify the levels of serum SOX2 DNA, analyze its diagnostic value and compare it with existing clinical parameters in lung cancer, and purpose to provide a novel tumor marker for lung cancer. Serum DNA was extracted from 94 lung cancer patients, 10 benign lung diseases, and 30 healthy volunteers, and then the levels of SOX2 DNA were quantified using real-time fluorescent quantitative polymerase chain reaction (FQ-PCR). The data were analyzed by statistical software SPSS14.0. The present results show that serum SOX2 DNA level in lung cancer group was higher compared to the levels in benign lung diseases group (u = 102.0, p < 0.001) or healthy group (u = 140.0, p < 0.001), and it was closely associated with TNM stage, histopathological type, and tumor size (p = 0.031, p = 0.012, and p = 0.010, respectively). However, serum SOX2 DNA levels of lung cancer patients were not associated with age, gender, smoking status, lymph node metastasis, or tumor differentiation (p > 0.05). ROC curve showed a sensitivity of 78.9% and a specificity of 82.5% for the ability of serum SOX2 DNA to detect lung cancer at the cutoff value of 1,078.3 copies/ul. Furthermore, we assessed the associations of serum SOX2 levels with clinical existing lung tumor markers, such as squamous cell carcinoma antigen, cytokeratin fragment 21-1, and neuron-specific enolase. The sensitivity was increased from 24.9, 66.1, and 39.1 to 84.2, 92.8, and 87.5%, respectively, by the combination of serum SOX2 DNA. Taken together, quantification of serum SOX2 DNA by FQ-PCR may serve as a novel accessory diagnostic tool for the clinical screening and detection of lung cancer.

Clinical significance of serum transforming growth factor-ß1 in lung cancer.

BACKGROUND: Transforming growth factor-ß1 (TGF-ß1) plays a critical role in human cancer development. Present study aimed to explore the clinical significance of serum TGF-ß1 levels in patients with lung cancer and analyze the relationship between TGF-ß1 and existing tumor markers for lung cancer. METHODS: Serum was collected from 118 patients with lung cancer and 40 healthy volunteers. Serum TGF-ß1 levels were measured by enzyme-linked immunosorbent assay (ELISA), and the association with various clinical characteristics was analyzed. The diagnostic value of TGF-ß1 was assessed alone and in combination with existing tumor markers for lung cancer. RESULTS: Serum TGF-ß1 levels were significantly higher in patients with lung cancer compared to healthy volunteers [0.6 × 10(5) (0.4 × 10(5), 0.9 × 10(5))pg/ml vs 0.5 × 10(5) (0.3 × 10(5), 0.7 × 10(5))pg/ml, P=0.040]. Although there was a positive correlation between serum TGF-ß1 levels and advanced stages, the significant difference was not found between early stages and advanced stages (P=0.116). The ability of serum TGF-ß1 to discriminate lung cancer at a cutoff value of 79,168 pg/ml exhibited sensitivity of 30.6% and specificity of 97.5%. Serum TGF-ß1 levels were correlated to cytokeratin fragment 21-1 (CYFRA21-1; R=0.308, P=0.020) and neuron-specific enolase (NSE; R=0.558, P=0.003). The diagnostic accuracy rates for the existing lung-tumor markers, as SCC, CYFRA21-1, and NSE, were increased from 20.0%, 34.6%, and 45.9% to 48.9%, 51.7%, and 54.5%, respectively by the inclusion of serum TGF-ß1 levels. CONCLUSION: Quantification of serum TGF-ß1 levels by ELISA may provide a novel complementary tool for the clinical diagnosis of lung cancer.

Clinical significance of serum mitochondrial DNA in lung cancer.

OBJECTIVES: The aim of the study was to investigate the clinical significance of serum mitochondrial DNA (mtDNA) in lung cancer. DESIGN AND METHODS: Serum mtDNA from 65 lung cancer patients, 20 patients with benign lung diseases and 55 healthy individuals was quantified using real-time fluorescent quantitative polymerase chain reaction (FQ-PCR). Data were analyzed using statistical software SPSS 13.0. RESULTS: Serum mtDNA levels in lung cancer patients were significantly higher, compared to those in patients with benign lung diseases and healthy individuals (u=108, p=0.000; u=293, p=0.000), and closely associated with TNM stage (p=0.01). The use of serum mtDNA facilitated detection of lung cancer at a cutoff value of 0.74×104 copies/µL with a sensitivity of 86.2% and specificity of 80.7%. However, serum mtDNA levels were not associated with patient age, gender, histological type, and lymph node metastasis (p>0.05). CONCLUSIONS: Quantification of serum mtDNA using FQ-PCR potentially serves as a novel complementary tool to improve the clinical screening and detection of lung cancer.

Quantification of serum HBXAP DNA in lung cancer patients by quantitative fluorescent polymerase chain reaction.

Hepatitis B virus x associated protein (HBXAP), as a subunit of chromatin remodeling and spacing factor, plays a critical role in cancer development through gene amplification. In this study, we aimed to quantify the levels of serum HBXAP DNA, to analyze and compare its diagnostic value with existing clinical parameters in lung cancer, and to potentially provide a novel tumor marker for lung cancer. Serum HBXAP DNA from 65 lung cancer patients and 20 healthy controls was quantified using real-time fluorescent quantitative polymerase chain reaction (FQ-PCR) analysis. The data were analyzed by statistical software SPSS 13.0. We found that serum HBXAP DNA levels in lung cancer patients were higher compared to healthy controls (u = 219.0, p = 0.001) and were closely associated with TNM stage and lymph node metastasis (p = 0.015 and p = 0.016, respectively). However, serum HBXAP DNA levels were not associated with patient age, gender, smoking status, histological type, or tumor size (p > 0.05). We identified a sensitivity of 61.9 % and a specificity of 93.7 % for the ability of HBXAP DNA levels to detect lung cancer at a cutoff value of 1,557.6 copies/µl. The sensitivity for existing lung-tumor markers, such as squamous cell carcinoma antigen, cytokeratin fragment 21-1, and neuron specific enolase, was increased from 35.7 %, 53.5 %, and 56.0 % to 75.0 %, 86.0 %, and 80.0 %, respectively, by inclusion of serum HBXAP DNA. Taken together, quantification of serum HBXAP DNA by FQ-PCR could potentially serve as a novel complementary tool for the clinical screening and detection of lung cancer.