Rapid Discovery of Substances with Anticancer Potential from Marine Fungi Based on a One Strain-Many Compounds Strategy and UPLC-QTOF-MS.

The secondary metabolites of marine fungi with rich chemical diversity and biological activity are an important and exciting target for natural product research. This study aimed to investigate the fungal community in Quanzhou Bay, Fujian, and identified 28 strains of marine fungi. A total of 28 strains of marine fungi were screened for small-scale fermentation by the OSMAC (One Strain-Many Compounds) strategy, and 77 EtOAc crude extracts were obtained and assayed for cancer cell inhibition rate. A total of six strains of marine fungi (P-WZ-2, P-WZ-3-2, P-WZ-4, P-WZ-5, P56, and P341) with significant changes in cancer cell inhibition induced by the OSMAC strategy were analysed by UPLC-QTOF-MS. The ACD/MS Structure ID Suite software was used to predict the possible structures with inhibitory effects on cancer cells. A total of 23 compounds were identified, of which 10 compounds have been reported to have potential anticancer activity or cytotoxicity. In this study, the OSMAC strategy was combined with an untargeted metabolomics approach based on UPLC-QTOF-MS to efficiently analyse the effect of changes in culture conditions on anticancer potentials and to rapidly find active substances that inhibit cancer cell growth.

Nasogastric tube feeding improves nutritional status and physical state in esophageal cancer patients during chemoradiotherapy: a retrospective study.

OBJECTIVE: To compare the complication rates, nutritional status, and physical state between esophageal cancer (EC) patients managed by nasogastric tube (NGT) feeding versus those managed by oral nutritional supplementation (ONS) during chemoradiotherapy. METHODS: EC patients undergoing chemoradiotherapy managed by nonintravenous nutritional support in our institute were retrospectively recruited and divided into an NGT group and an ONS group based on the nutritional support method. The main outcomes, including complications, nutritional status, and physical state, were compared between groups. RESULTS: The baseline characteristics of EC patients were comparable. There were no significant differences in the incidence of treatment interruption (13.04% vs. 14.71%, P = 0.82), death (2.17% vs. 0.00%, P = 0.84), or esophageal fistula (2.17% vs. 1.47%, P = 1.00) between the NGT group and ONS group. Body weight loss and decrease in albumin level were significantly lower in the NGT group than in the ONS group (both P < 0.05). EC patients in the NGT group had significantly lower Nutritional Risk Screening 2002 (NRS2002) and Patient-Generated Subjective Global Assessment (PG-SGA) scores and significantly higher Karnofsky Performance Status (KPS) scores than patients in the ONS group (all P < 0.05). The rates of grade > 2 esophagitis (10.00% vs. 27.59%, P = 0.03) and grade > 2 bone marrow suppression (10.00% vs. 32.76%, P = 0.01) were significantly lower in the NGT group than in the ONS group. There were no significant differences in the incidence of infection and upper gastrointestinal disorders or therapeutic efficacy between groups (all P > 0.05). CONCLUSIONS: EN through NGT feeding leads to significantly better nutritional status and physical state in EC patients during chemoradiotherapy than EN via ONS. NGT may also prevent myelosuppression and esophagitis..

Postoperative health-related quality of life in children with congenital heart disease: a short-term follow-up study.

OBJECTIVE: This study aimed to explore changes in health-related quality of life in children with congenital heart disease from pre-surgery to 6 months after surgery. METHODS: A total of 87 children aged 2-12 years who underwent cardiac surgery in a provincial hospital in China from January 2021 to June 2021 were selected. After 6 months, the quality of life of all children was retrospectively analyzed. The Chinese version of the Pediatric Quality of Life Inventory 4.0 Scale was used to assess the quality of life of children before and after surgery. RESULTS: Parents of 85 children and 33 children aged 5-12 years completed the questionnaires. After surgical treatment, the quality of life scores reported by parents of children of all ages were significantly higher than those before surgery, the P value < 0.05; the self-evaluated quality of life scores of children of different ages were significantly higher than those before surgery, the P value < 0.05. CONCLUSION: Surgical treatment can improve the health-related quality of life of children with congenital heart disease.

GATA3 positively regulates PAR1 to facilitate in vitro disease progression and decrease cisplatin sensitivity in neuroblastoma via inhibiting the hippo pathway.

GATA binding protein 3 (GATA3) is reported to critically involved in the pathogenesis of neuroblastoma (NB). This study investigated the specific role and mechanism of GATA3 in NB progression. JASPAR was utilized to predict GATA3's downstream targets, whose binding relation with GATA3 was inspected by a dual-luciferase reporter assay. NB cell lines underwent transfection of GATA3/protease-activated receptor 1 (PAR1) overexpression plasmids or shGATA3, followed by cisplatin treatment. NB cell sensitivity to cisplatin, viability, migration, invasion, cell cycle progression and apoptosis were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, wound healing assay, transwell assay and flow cytometry, respectively. Expressions of GATA3, PAR1, epithelial-mesenchymal transition-related molecules (N-Cadherin and Vimentin), hippo pathway-related molecules (mammalian Ste20-like kinase (Mst)1, Mst2, Mps one binding (Mob) 1, phosphorylated (p)-Mob1, Yes-associated protein (YAP) and p-YAP) in NB tissues and cell lines were assessed by western blot or qRT-PCR. GATA3 expression was increased in NB tissues and cells. GATA3 overexpression increased NB cell viability, promoted migration, invasion, and cell cycle progression, increased the expressions of N-Cadherin, Vimentin and YAP, decreased the expressions of Mst1, Mst2, Mob1, p-Mob1, p-YAP and the ratio of p-YAP to YAP, and attenuated cisplatin-induce cell apoptosis, which GATA3 knockdown induced the opposite effect. GATA3 directly targeted PAR1, whose overexpression increased NB cell viability, inhibited the hippo pathway, and attenuated cisplatin-induce cell apoptosis, and reversed GATA3 knockdown-induced effect on these aspects. GATA3 positively regulates PAR1 to facilitate in-vitro disease progression and decrease cisplatin sensitivity in NB via inhibiting the hippo pathway.

E2F1 induced neuroblastoma cell migration and invasion via activation of CENPE/FOXM1 signaling pathway.

Background: Neuroblastoma (NB) is a common malignancy occurring in infants and young children. Centrosome-associated protein E (CENPE) is a kinetochore-related motor protein highly expressed in NB, with the mechanism largely unknown. This study is committed to investigating the role and mechanism of CENPE in NB.Method: Short hairpin RNAs targeting CENPE and E2F transcription factor 1 (shCENPE and shE2F1) and CENPE overexpression plasmid were transfected into IMR-32 and SK-N-SH cells. The mRNA expressions of CENPE, N-Cadherin, Vimentin, and proliferating cell nuclear antigen (PCNA) in NB cells were detected by qRT-PCR. The viability, migration, and invasion of cells were tested through cell function experiments. Western blot was applied to detect the protein levels of N-Cadherin, Vimentin, PCNA, CENPE and Forkhead box M1 (FOXM1). The relationship between CENPE and E2F1 was verified by dual-luciferase reporter assay, while the interaction between FOXM1 and CENPE in NB cells was analyzed by rescue experiments.Results: CENPE expression was upregulated in NB cells from metastatic sites. Silencing of CENPE suppressed the NB cell viability, migration, and invasion; and decreased N-Cadherin, Vimentin and PCNA expressions, while overexpressed CENPE did oppositely. E2F1 positively targeted CENPE and CENPE partly reversed the effects of shE2F1 on repressing NB cell viability, migration, invasion and the activation of CENPE/FOXM1 signaling pathway. In addition, silenced FOXM1 partly offset the effects of CENPE on promoting NB cell migration and invasion.Conclusion: E2F1 induces NB cell migration and invasion via activating CENPE/FOXM1 pathway.

Identification of Prognostic lncRNA Related to the Immune Microenvironment of Soft Tissue Sarcoma.

BACKGROUND: Soft tissue sarcoma is a malignant tumor with high degree of malignancy and poor prognosis, originating from mesenchymal tissue. Long noncoding RNAs (lncRNAs) are involved in various biological and pathological processes in the body. They perform preprocessing, splicing, transport, degradation, and translation of mRNA to achieve posttranscriptional level regulation, resulting in the occurrence, invasion, and metastasis of tumors. Therefore, they are highly relevant with regard to early diagnoses and as prognostic indicators. OBJECTIVE: The objective of the present study was to identify immune microenvironment-related lncRNAs that can be used to predict soft tissue sarcomas. METHODS: Clinical data and follow-up data were obtained from the cBioPortal database, and RNA sequencing data used for the model structure can be accessed from The Cancer Genome Atlas (TCGA) database. LncRNAs were screened by differential expression analysis and coexpression analysis. The Cox regression model and Kaplan-Meier analysis were used to study the association between lncRNAs and soft tissue sarcoma prognosis in the immune microenvironment. Unsupervised cluster analysis was then completed to discover the impact of screening lncRNAs on disease. We constructed an mRNA-lncRNA network by Cytoscape software. Finally, qRT-PCR was used to verify the difference in the expression of the lncRNAs in normal cells and sarcoma cells. RESULTS: Unsupervised cluster analysis revealed that the 210 lncRNAs screened showed strong correlation with the tumor immune microenvironment. Two signatures containing seven and five lncRNAs related to the tumor microenvironment were constructed and used to predict overall survival (OS) and disease-free survival (DFS). The Kaplan-Meier (K-M) survival curve showed that the prognoses of patients in the high-risk and low-risk groups differed significantly, and the prognosis associated with the low-risk group was better than that associated with the high-risk group. Two nomograms with predictive capabilities were established. qRT-PCR results showed that the expression of AC108134.3 and AL031717.1 was significantly different in normal and sarcoma cells. CONCLUSION: In summary, the experimental results showed that lncrnA associated with immune microenvironment was related to tumor, which may provide a new idea for immunotherapy of STS.

The effects of eye masks on post-operative sleep quality and pain in school-age children with CHD.

OBJECTIVE: This study aimed to explore the effects of eye masks on the sleep quality and pain of school-age children with CHD after surgery. METHODS: Forty school-age children with CHD who underwent open-heart surgery in the Cardiac Surgery Department of a provincial hospital in China from January 2020 to December 2020 were selected. The children were randomly divided into the experimental group (n = 20) and the control group (n = 20). Children in the control group were given routine sleep care, and the children in the experimental group were given a sleep intervention with eye masks for three nights following the removal of tracheal intubation. The Pittsburgh Sleep Quality Index was used to evaluate the sleep quality of the children. The Children's Pain Behaviour Scale was used to evaluate the pain of the children. RESULTS: After three nights of receiving the eye masks intervention, the sleep quality scores of the children in the experimental group were significantly lower than those of the control group, the difference was statistically significant (p < 0.05) and the sleep quality of the children in the experimental group was higher. The pain scores of the children in the experimental group were significantly lower than those of the children in the control group, the difference was statistically significant (p < 0.05), and the children in the experimental group suffered less post-operative pain. CONCLUSION: Eye masks are a simple, safe and economical intervention, that is beneficial for improving the post-operative sleep quality and relieving post-operative pain in school-age children with congenital heart disease.

Effect of WeChat follow-up education on breastfeeding efficiency of infants after congenital cardiac surgery and parents' satisfaction: A short-term follow-up study.

AIM: This study aimed to investigate the impact of WeChat follow-up education on infants' breastfeeding efficiency after congenital cardiac surgery and parents' satisfaction. METHODS: A prospective study was conducted in a provincial hospital in China. Sixty participants were divided into two groups: 30 participants in the study group received WeChat follow-up health education, and 30 participants in the control group received postoperative routine nursing education for infants after congenital cardiac surgery. The infants' breastfeeding efficiency, parents' satisfaction and relevant clinical data were recorded and analysed. RESULTS: After the WeChat follow-up intervention, the breastfeeding efficacy score, the parents' satisfaction score and the exclusive breastfeeding rate in the study group were significantly higher than those in the control group (P < 0.05). There was no significant difference in the incidence of feeding intolerance, abdominal distension, dyspeptic diarrhoea, weight gain or recurrent vomiting between the two groups during the 3-month follow-up period. CONCLUSION: WeChat education can improve infants' breastfeeding efficiency after congenital cardiac surgery and can improve parents' satisfaction and exclusive breastfeeding rate during the short-term follow-up period.

Comparison of the Effect of Breast Milk and Sodium Bicarbonate Solution for Oral Care in Infants with Tracheal Intubation After Cardiothoracic Surgery.

Background: This study aimed to explore the effect of breast milk and sodium bicarbonate solution used in oral care of infants with tracheal intubation after cardiothoracic surgery. Methods: A randomized clinical controlled trial was conducted in a provincial hospital in China. Fifty infantile patients were randomly divided into two groups: the patients in the study group (n = 25) used breast milk for oral care and the patients in the control group (n = 25) used sodium bicarbonate solution for oral care. The relevant clinical data were recorded, including the mechanical ventilation duration, length of intensive care unit (ICU) stay, length of hospital stay, and complications. Results: The length of ICU stay, length of hospital stay, and duration of mechanical ventilation were shorter in the study group, but the difference was not statistically significant (p > 0.05). However, the incidence of thrush and ventilator-associated pulmonary infection in the study group was significantly lower than that in the control group (p < 0.05). Conclusion: The use of breast milk for oral care has a positive effect on the prevention of thrush and ventilator-associated pulmonary infection in infants with tracheal intubation after cardiothoracic surgery.

The effect of music therapy on pain, anxiety and depression in patients after coronary artery bypass grafting.

OBJECTIVE: The purpose of this study was to explore the effects of music therapy on pain, anxiety and depression in patients after coronary artery bypass grafting. METHODS: A retrospective study of 99 patients after coronary artery bypass from January 2017 to January 2019 was conducted in a cardiac center in China. According to the different interventions, all the participants were divided into 3 groups: group A: music therapy; group B: rest without music therapy; and group C: conventional treatment. The Numerical Rating Scale (NRS), Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) were used to measure the patient's pain, anxiety and depression before and after 30 min of the intervention. RESULTS: There were no significant differences in the NRS, SDS and SAS scores between the three groups of patients before the intervention. After 30 min of music therapy, the NRS, SDS and SAS scores of patients in group A were significantly lower than those before music therapy, and the differences were statistically significant. However, before and after the intervention in groups B and C, the NRS, SDS and SAS scores were not statistically significant. By comparison among the three groups after 30 min of intervention, the NRS, SDS and SAS scores in patients in group A were significantly lower than those in groups B and C, and the differences were statistically significant. The scores were not significantly different between groups B and C. CONCLUSION: Music therapy can effectively alleviate the pain, anxiety and depression of patients after coronary artery bypass grafting.

Foretinib Enhances the Radiosensitivity in Esophageal Squamous Cell Carcinoma by Inhibiting Phosphorylation of c-Met.

As a crucial event involved in the metastasis and relapse of esophageal cancer, c-Met overexpression has been considered as one of the culprits responsible for the failure in patients who received radiochemotherapy. Since c-Met has been confirmed to be pivotal for cell survival, proliferation and migration, little is known about its impact on the regulation of radiosensitivity in esophageal cancer. The present study investigated the radiosensitization effects of c-Met inhibitor foretinib in ECA-109 and TE-13 cell lines. Foretinib inhibited c-Met signaling in a dose-dependent manner resulting in decreases in the cell viability of ECA-109 and TE-13. Pretreatment with foretinib synergistically prompted cell apoptosis and G2/M arrest induced by irradiation. Moreover, decreases ability of DNA damage repair was also observed. In vivo studies confirmed that the combinatorial use of foretinib with irradiation significantly diminishes tumor burden compared to either treatment alone. The present findings implied a crucial role of c-Met in the modulation of radiosensitization in esophageal cancer, and foretinib increased the radiosensitivity in ECA-109 and TE-13 cells mainly via c-Met signaling, highlighting a novel profile of foretinib as a potential radiosensitizer for the treatment of esophageal cancer.

The mechanisms of radioresistance in esophageal squamous cell carcinoma and current strategies in radiosensitivity.

Esophageal cancer is the eighth most common cancer and the sixth leading cause of cancer-related death worldwide. Surgery is the primary form of treatment, but the survival is poor, especially for patients with locally advanced esophageal cancer. Radiotherapy has been a critical treatment option that may be combined with chemotherapy in patients with unresectable esophageal cancer. However, resistance to chemoradiotherapy might result in treatment failures and cancer relapse. This review will mainly focus on the possible cellular mechanisms and tumor-associated microenvironmental (TAM) factors that result in radioresistance in patients with esophageal cancer. In addition, current strategies to increase radiosensitivity, including targeted therapy and the use of radiosensitive biomarkers in clinical treatment, are discussed in this review.

Culture and Identification of Bone Marrow Mesenchymal Stem Cells from Enhanced Green Fluorescent Protein-transgenic Rats.

OBJECTIVE: To isolate, culture, and identify bone marrow mesenchymal stem cells (BMSCs) from enhanced green fluorescent protein (EGFP)-transgenic rats in vitro. METHODS: Bone marrows were isolated from tibia and femur of healthy EGFP-transgenic rats of specific pathogen free (SPF) grade. Then,the whole bone marrow adherent method was used for isolation,culture,and purification of BMSCs. The morphological change was noted by continuous observation under inverted fluorescence microscope. The growth curve of cells was drawn through the method of CCK-8 and the proliferation compared with wild type BMSCs. The surface markers of BMSCs were detected by flow cytometry. The BMSCs were induced to differentiate into osteoblasts, adipocytes, and chondrocytes lineages. The EGFP-BMSCs were transplanted into the rats intravenously, and the expression of GFP was detected. RESULTS: BMSCs stably expressing EGFP gene were obtained successfully, with the fusiform-shaped appearance and the forming of circinate cell colonies. The growth curve of EGFP-MSCs showed the characteristic of active proliferation, showing no significant difference compared with the wild-type BMSCs. The expression rates of the surface markers of BMSCs CD29, CD90, CD34, CD49d, and CD45 were 99.4%, 96.4%, 0.171%, 0.049%, and 0.038%. The GFP were detected in lung 3 days after transplantation. After osteogenic, adipogenic, and chondrogenic induction, oil red-O and alizarin red positive signals and toluidine blue positive cells were detected. CONCLUSIONS: High-purity BMSCs stably expressing green fluorescent protein gene can be cultured using the whole bone marrow adherent method. EGFP does not affect the stem cell properties and expresses stably after transplantation. The cells can be used as seed cells for subsequent research.

[Dynamics of peripheral blood B lymphocytes and natural killer cells in patients with severe acute respiratory syndrome].

OBJECTIVE: To study the dynamics of peripheral blood B lymphocytes and natural killer (NK) cells in patients with severe acute respiratory syndrome (SARS). METHODS: The absolute numbers of peripheral blood B lymphocytes and NK cells in 602 serial samples from 240 patients with SARS were counted, using flow cytometry, and compared with that of normal population. RESULTS: The absolute numbers of peripheral blood B lymphocytes and NK cells in SARS patients were significantly lower than that of the normal population (P < 0.001) and were much lower in SARS patients with severe or extremely severe types, as compared with that of moderate or mild type cases (P < 0.001). The amount of B lymphocytes in recovery SARS patients increased at the 2nd week after onset, and gradually becoming normal at the 5th week of the disease onset. The number of NK cells was in the low level at onset, and keep decreasing at the 2nd week. However, it was increasing with the recovery of the disease, but did not reach to normal level at the 5th week after onset. CONCLUSION: The absolute numbers of peripheral blood B lymphocytes and NK cells were associated with the severity of the disease, and detection of these two kinds of cells was useful for predicting the prognosis of SARS.