Health-related quality of life of COVID-19 patients after discharge: A multicenter follow-up study.

AIMS AND OBJECTIVES: To determine the health-related quality of life (HRQoL) of COVID-19 patients after discharge and its predicting factors. BACKGROUND: COVID-19 has caused a worldwide pandemic and led a huge impact on the health of human and daily life. It has been demonstrated that physical and psychological conditions of hospitalised COVID-19 patients are impaired, but the studies focus on physical and psychological conditions of COVID-19 patients after discharge from hospital are rare. DESIGN: A multicentre follow-up study. METHODS: This was a multicentre follow-up study of COVID-19 patients who had discharged from six designated hospitals. Physical symptoms and HRQoL were surveyed at first follow-up (the third month after discharge). The latest multiple laboratory findings were collected through medical examination records. This study was performed and reported in accordance with STROBE checklist. RESULTS: Three hundred eleven patients (57.6%) were reported with one or more physical symptoms. The scores of HRQoL of COVID-19 patients at third month after discharge, except for the dimension of general health, were significantly lower than Chinese population norm (p < .001). Results of logistic regression showed that female (odds ratio (OR): 1.79, 95% confidence interval (CI): 1.04-3.06), older age (≥60 years) (OR: 2.44, 95% CI: 1.33-4.47) and the physical symptom after discharge (OR: 40.15, 95% CI: 9.68-166.49) were risk factors for poor physical component summary; the physical symptom after discharge (OR: 6.68, 95% CI: 4.21-10.59) was a risk factor for poor mental component summary. CONCLUSIONS: Health-related quality of life of discharged COVID-19 patients did not come back to normal at third month after discharge and affected by age, sex and the physical symptom after discharge. RELEVANCE TO CLINICAL PRACTICE: Healthcare workers should pay more attention to the physical and psychological rehabilitation of discharged COVID-19 patients. Long-term follow-up on COVID-19 patients after discharge is needed to determine the long-term impact of COVID-19.

Upregulation of MALAT-1 and its association with survival rate and the effect on cell cycle and migration in patients with esophageal squamous cell carcinoma.

The aim of this study is to investigate whether metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) can be used as a potential therapy target for human esophageal squamous cell carcinoma. MALAT-1 expression levels were detected in 137 paired EC samples and adjacent nonneoplastic tissues. Human esophageal carcinoma cell lines EC9706 and KYSE150 were transfected with MALAT-1 small interference RNA. Cell proliferation, migration/invasion ability, cell cycle, and apoptosis were assessed. MALAT-1 expressed higher levels in esophageal cancer tissues when compared with paired adjacent normal tissues. This high expression was associated with a decreased survival rate. MALAT-1 knockdown induced a decrease in proliferation-enhanced apoptosis, inhibited migration/invasion, and reduced colony formation and led to cell cycle arrest at the G2/M phase. These data indicates that MALAT-1 could be exploited for therapeutic benefit.

Overexpressed miR-106b-5p promotes epithelial-mesenchymal transition in endometriosis by targeting PTEN.

The miRNA miR-106b-5p expression is elevated in endometriotic lesions. This study aimed to detect miR-106b-5p expression in human endometrial stromal cells and explore the molecular mechanisms regulating proliferation, migration, and epithelial-mesenchymal transition (EMT) of these cells. Cell proliferation, migration, and EMT were compared after miR-106b-5p upregulation. The downstream target of miR-106b-5p was verified using bioinformatic, luciferase reporter, and rescue assays. The relationship between miR-106b-5p and the target genes was also analyzed. Results showed that the expression of miR-106b-5p in endometriotic lesions was higher than that in non-lesion tissues. Furthermore, upregulation of miR-106b-5p promoted the proliferation, migration, and EMT of human endometrial stromal cells. Additionally, phosphatase and tensin homolog ten (PTEN) was found to be negatively correlated with miR-106b-5p expression. Low expression levels of PTEN were significantly correlated with cell proliferation, migration, and EMT. High PTEN expression could rescue the effect of miR-106b-5p on cell capacity. In conclusion, miR-106b-5p modified human endometrial stromal cell function by sponging PTEN. These findings indicate that inhibition of miR-106b-5p may be an effective therapeutic strategy for endometriosis.

Clinical efficacy of low-dose emetine for patients with COVID-19: a real-world study.

OBJECTIVE: Emetine, an isoquinoline alkaloid that is enriched at high concentrations in the lung, has shown potent in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The aim of this study was to better understand the effectiveness of low-dose emetine for patients with coronavirus disease 2019 (COVID-19). METHODS: In this real-world study, 63 patients with mild or common COVID-19 were recruited from Wuhan Fangcang Shelter Hospital and five COVID-19-designated hospitals in Anhui Province, China from February to March 2020. Thirty-nine patients from Wuhan Fangcang Shelter Hospital were assigned to a pragmatic randomized controlled clinical trial, and 24 patients from the 5 COVID-19-designated hospitals in Anhui Province underwent a real-world study. The medication course of emetine was less than 10 days. The main symptoms and adverse reactions of all patients were observed and recorded. The primary outcome measure was the time required for a negative SARS-CoV-2 RNA result or the negative result rate on day 10. Secondary outcomes included axillary temperature, transcutaneous oxygen saturation, and respiratory frequency recovery. The study was approved by the Ethics Committee of The First Affiliated Hospital of Anhui Medical University on February 20, 2019 (approval No. PJ2020-03-19) and was registered with the Chinese Clinical Trial Registry on February 20, 2019 (registration number: ChiCTR2000030022). RESULTS: The oxygen saturation values were higher in the treatment group than in the control group on the first day after enrollment for patients treated at Fangcang Shelter Hospital. The axillary body temperature, respiratory rate, and oxygen saturation among patients in Fangcang Shelter Hospital were related to the time effect but not to the intervention measures. The respiratory rate and oxygen saturation of patients in the Anhui designated hospitals were related to the intervention measures but not to the time effect. The axillary body temperature of patients in Anhui designated hospitals was related to the time effect but not to the intervention measures. CONCLUSION: Our preliminary study shows that low-dose emetine combined with basic conventional antiviral drugs improves clinical symptoms in patients with mild and common COVID-19 without apparent adverse effects, suggesting that moderately increased doses of emetine may have good potential for treatment and prevention of COVID-19.

Identification and potential value of candidate microRNAs in granulosa cells of polycystic ovary syndrome.

BACKGROUND: Polycystic Ovary Syndrome (PCOS) is a major cause of anovulatory infertility. Some studies showed that miRNAs were used as diagnostic/prognostic biomarkers for various diseases. OBJECTIVE: To identify candidate miRNAs in Granulosa Cells (GCs) of PCOS and evaluate their potential values for PCOS diagnosis. METHODS: We screened differentially expressed miRNAs in GCs between PCOS and controls by the microarray data from the GEO database. GCs were collected from 21 controls and 24 PCOS. The candidate miRNAs were verified by qRT-PCR. The correlation was investigated between candidate miRNAs and clinical characteristics in participants. Diagnostic value of candidate miRNAs was analyzed by receiver operating characteristic (ROC) curve. RESULTS: Seven miRNAs were differentially expressed in PCOS compared with controls. Furthermore, the validation results demonstrated that hsa-miR-3188 and hsa-miR-3135b showed higher levels in GCs with PCOS patients (p< 0.05). In addition, the expressions of hsa-miR-3188 and hsa-miR-3135b were negative correlated with FSH and hsa-miR-3188 was positive correlated with BMI (p< 0.05). ROC analysis indicated that hsa-miR-3188 and hsa-miR-3135b could differentiate PCOS from controls, and the hsa-miR-3188/3135b improved the predictive accuracy for PCOS. CONCLUSIONS: The expressions of hsa-miR-3188 and hsa-miR-3135b in human GCs were significantly associated with PCOS. Moreover, the hsa-miR-3188/3135b has certain diagnostic value for distinguishing PCOS.

MicroRNA-506 inhibits esophageal cancer cell proliferation via targeting CREB1.

MicroRNAs (miRNAs) act as key regulators of multiple cancers. MicroRNA-506 (miR-506) functions as a tumor suppressor in various types of cancers. However, its role in esophageal cancer remains unclear. In our study, we found that miR-506 was significantly down-regulated in esophageal cancer tissues and cell lines. In vitro assay, our results showed that ectopic over-expression of miR-506 inhibited esophageal cancer cells proliferation, meanwhile, cells proliferation was promoted by miR-506 inhibition. In exploring mechanisms underlying the inhibitive role, we found that miR-506 significantly decreased the expression and transcription activity of cAMP responsive element binding protein 1 (CREB1). CREB1, tumor oncogene, exhibited significantly promote effect on esophageal cancer cell proliferation. Taken together, our data identify a new role of miR-506 in esophageal cancer involving CREB1 suppression.

Expression of long non-coding RNA ZEB1-AS1 in esophageal squamous cell carcinoma and its correlation with tumor progression and patient survival.

BACKGROUND: LncRNA ZEB1-AS1 has been identified as a tumor oncogene in hepatocellular carcinoma. However, the clinical significance in esophageal squamous cell carcinoma (ESCC) is still unknown. The aim of this study was to explore ZEB1-AS1 expression levels and evaluated its clinical significance in ESCC patients. METHODS: LNCRNA ZEB1-AS1 expression was determined by quantitative real-time PCR (QRT-PCR) in 87 pairs of ESCC specimens and adjacent non-tumor tissues. Then, the association of ZEB1-AS1 expression with clinicopathological factors or survival of ESCC patients were determined. RESULTS: LNCRNA ZEB1-AS1 was found up-regulated in ESCC tissues compared to adjacent non-tumor tissues. Increased lncRNA ZEB1-AS1 expression was significantly associated with tumor grade, depth of invasion, and lymph node metastasis. Kaplan-Meier analysis revealed that ESCC patients with high ZEB1-AS1 expression had a poorer overall survival and disease-free survival. Furthermore, multivariate analysis suggested that ZEB1-AS1 expression was identified as an independent prognostic factor in patients with ESCC. CONCLUSION: These results indicated that lncRNA ZEB1-AS1 was associated with tumor progression and could be an independent prognostic factor for ESCC patients.

MiR-27a-3p promotes esophageal cancer cell proliferation via F-box and WD repeat domain-containing 7 (FBXW7) suppression.

Emerging evidence has suggested that dysregulation of microRNA-27a-3p (miR-27a-3p) may contribute to tumor development and progression in various types of cancers. However, its role in esophageal cancer is still unknown. In the present study, miR-27a-3p was significantly increased in esophageal squamous cell carcinoma (ESCC) tissues and cell lines. In esophageal cancer Eca109 cells, ectopic overexpression of miR-27a-3p promoted cell proliferation, meanwhile, cell proliferation was reduced by miR-27a-3p inhibition. Further studies showed that down-regulated miR-27a-3p expression could induced cell cycle arrest at the G1/S transition. In exploring mechanisms underlying the promotive role, our results revealed that miR-27a-3p markedly inhibited the expression of F-box and WD repeat domain-containing 7 (FBXW7). FBXW7, a tumor suppressor, exhibited significantly inhibitory effect on Eca109 cell proliferation. Thus our observations suggested that miR-27a-3p functioned as a tumor suppressor by targeting FBXW7. These findings indicated that miR-27a-3p could be considered as a potential therapeutic strategy for ESCC therapy.

Expression of flotillin-2 in human non-small cell lung cancer and its correlation with tumor progression and patient survival.

INTRODUCTION: Recent studies have revealed that flotillin-2 (FLOT2) played important roles in cancer progression. The aim of this study was to investigate the clinicopathologic and prognostic significance of FLOT2 expression in human non-small cell lung cancer (NSCLC). METHODS: Quantitative real-time PCR (qRT-PCR) was performed to detect FLOT2 mRNA expression in lung cancer cell lines, normal bronchial epithelial cells, 24 pairs of NSCLC tissues and matched adjacent non-tumor tissues. Immunohistochemistry (IHC) was performed to examine FLOT2 protein expression in paraffin-embedded tissues from 90 NSCLC patients. Statistical analyses were performed to evaluate the clinicopathological significance of FLOT2 expression. RESULTS: FLOT2 mRNA expression was evidently up-regulated in lung cancer cell lines and NSCLC tissues compared with normal bronchial epithelial cells and adjacent non-tumor tissues. In the 90 cases of tested NSCLC samples, FLOT2 protein level was positively correlated with tumor stage, and lymph node metastasis. Patients with high FLOT2 expression had shorter overall survival compared with the low FLOT2 expression group. Univariate and multivariate analyses indicated that high FLOT2 expression was an independent poor prognostic factor for NSCLC patients. CONCLUSIONS: Our findings provided that high FLOT2 expression was associated with poor outcomes in NSCLC patients, and FLOT2 could be a potential prognostic biomarker for lung cancer progression.

Expression of miR-32 in human non-small cell lung cancer and its correlation with tumor progression and patient survival.

INTRODUCTION: miR-32 has recently been found to be implicated in many critical processes in various types of human cancer. However, its clinical significance in human non-small cell lung cancer (NSCLC) has not yet been elucidated. In the present study, we investigated the expression of miR-32 in NSCLC and analyzed its association with clinical features and prognosis of NSCLC patients. METHODS: Quantitative real-time PCR (qRT-PCR) was used to measure expression level of miR-32 in lung cancer cell lines, normal bronchial epithelial cells, 90 pairs of tumor samples and adjacent non-tumor tissues. To determine its prognostic value, overall survival was evaluated using the Kaplan-Meier method. Univariate and multivariate analysis were performed using the Cox proportional hazard analysis. RESULTS: The expression of miR-32 was significantly decreased in lung cancer cell lines and NSCLC tissues compared with normal bronchial epithelial cells and adjacent non-tumor tissues (P < 0.05). This reduction of miR-32 was associated with tumor stage and lymph node metastasis (P < 0.05). Moreover, Kaplan-Meier analysis demonstrated that patients with low miR-32 expression had shorter overall survival time than those with high miR-32 expression (P < 0.05). Univariate analysis revealed statistically significant correlations between overall survival and miR-32 level, tumor stage and lymph node metastasis (P < 0.05). Furthermore, miR-32 levels, tumor stage and lymph node metastasis were independently associated with overall survival (P < 0.05). CONCLUSIONS: Our results provided the first evidence that down-regulation of miR-32 was correlated with NSCLC progression, and miR-32 might be a potential molecular biomarker for predicting the prognosis of patients.

Induction of apoptosis by chitosan/HPV16 E7 siRNA complexes in cervical cancer cells.

Consecutive expression of the high­risk human papillomavirus (HPV) oncoproteins, E6 and E7, is pivotal for malignant transformation and maintenance of the malignant phenotype. These oncogenes may be potential targets of gene silencing­based molecular therapies for human cervical cancer. The aim of the present study was to evaluate the efficacy of chitosan­based HPV16 E7 siRNA delivery and the chitosan/HPV16 E7 siRNA complex in the induction of apoptosis in CaSki cells constitutively expressing HPV16 E6 and E7. Chitosan/siRNA nanoparticles were prepared by adding a chitosan solution drop­wise to an equal volume of siRNA solution. Formation of the chitosan/siRNA complex was verified by gel retardation assays and the entry of siRNA into the cells was confirmed by fluorescence microscopy. Expression of HPV16 E7 was examined by western blot analysis and apoptotic cells were detected by TUNEL staining. Chitosan formed complexes with HPV16 E7 siRNA. The chitosan/siRNA nanoparticles were efficiently delivered into CaSki cells and were observed to induce apoptosis. In conclusion, chitosan is suitable for use as a carrier for delivery of siRNA into cancer cells. The delivery of chitosan/HPV16 E7 siRNA nanoparticles in vivo may serve as a promising therapy for cervical cancer.