Pediatric infection with the Omicron variant increases the risks of febrile seizures among COVID-19 infected children.

Background: The Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is less likely to cause severe disease in children than the other variants but has become an increasing cause of febrile seizures (FS) among children. In this case-control study, we aimed to examine the risk factors associated with FS in children infected with the COVID-19 Omicron variant and related treatment modalities. Methods: This retrospective case-control study includes 113 subjects infected with the COVID-19 Omicron variant, grouped into 45 cases (those with FS) and 68 controls (those without FS). Data on clinical features, laboratory parameters, and treatment modalities were collected and analyzed. Results: Approximately 5.74% of COVID-19 infected children developed COVID-19-associated FS. Children with COVID-19 and high body temperatures [RR 1.474; (95% CI: 1.196-1.818), p < 0.001], previous history of FS [RR 1.421; (95% CI: 1.088-1.855), p = 0.010], high procalcitonin levels [RR 1.140; (95% CI: 1.043-1.246), p = 0.048] and high neutrophil counts [RR 1.015; (95% CI: 1.000-1.029), p = 0.048] were more likely to experience FS than the controls. In contrast, children with COVID-19 and low eosinophil counts, low hemoglobin levels, and cough had a lower risk of developing FS [RR 0.494; (95% CI: 0.311-0.783), p = 0.003], [RR 0.979; (95% CI: 0.959-0.999), p = 0.044]; and [RR 0.473 (95% CI 0.252-0.890), p = 0.020]; respectively. Children with FS received more anti-flu medications than those without. Conclusion: A significant increase in FS was observed in children with Omicron SARS-CoV-2 infection. A higher body temperature, a history of FS, a higher procalcitonin level, and a high neutrophil count were all associated with an increased risk of FS in children with COVID-19. The risk of developing FS was lower in children with COVID-19 and low eosinophil counts and hemoglobin levels than in those without.

FKBP11 upregulation promotes proliferation and migration in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer related deaths world over. Early diagnosis and effective treatment monitoring significantly improves patients' outcomes. FKBP11 gene is highly expressed in HCC and could play a role in its development, early diagnosis and treatment. OBJECTIVE: This study aimed to evaluate the expression of FKBP11 in HCC, its correlation with patients' clinical characteristics and potential role in HCC development. METHODS: Expression was determined by bioinformatics analysis, quantitative real-time PCR, western blot, and immunohistochemistry. CCK-8, Transwell and wound healing assays were used to investigate involvement in HCC development. RESULTS: FKBP11 was significantly upregulated in HCC cells, tissues and blood (all p< 0.001). Its receiver operator characteristic (ROC) curve had an AUC of 0.864 (95% CI: 0.823-0.904), at a sensitivity of 0.86 and specificity of 0.78 indicating a good diagnostic potential in HCC. Its expression was markedly reduced after surgery (p< 0.0001), indicating a potential application in HCC treatment follow-up. Knockdown of FKBP11 in HCC cells attenuated proliferation and migration, suggesting a possible role in HCC pathogenesis. CONCLUSION: This study thus found that FKBP11 is upregulated in HCC, and the upregulation promotes HCC development. FKBP11 levels are significantly reduced post-surgery and could be a potential diagnostic and prognostic marker for HCC.

Optimum cycles of induction chemotherapy in concurrent chemo-radiotherapy management of unresectable stage III non-small cell lung cancer: Results from a single institutional database.

Induction chemotherapy (IC) prior to concurrent chemo-radiotherapy is the recommended treatment for unresectable stage III non-small cell lung cancer (NSCLC). However, the optimum number of IC cycles for improved survival outcomes is still not known. Here, we assessed the efficacy of 2 or more cycles of IC for unresectable stage III NSCLC patients from our hospital. Data on unresectable stage III NSCLC patients treated with IC + concurrent chemo-radiotherapy at our hospital between 2018 and 2022 were retrieved and analyzed, and survival outcomes compared between IC = 2 and IC > 2 patients. Univariate and multivariate Cox regression, and Chi-square or Fisher exact test were used to assess prognosis and acute toxicity profiles. One hundred twenty-six patients were recruited; 90 for IC = 2 and 36 for IC > 2. Median follow-up time was 26 months [IQR 16-38]. Three-year overall survival was not statistically significant between the 2 groups (77.8% vs 75.0%, P = .453). Distant metastasis free survival, loco-regional recurrence free survival and progression free survival were also not significant, (90.0% vs 86.1%, P = .068), 97.8% vs 97.2%, P = .056), and (73.3% vs 66.7%, P = .446) respectively. Univariate and multivariate Cox regression analysis revealed smoking, T_stage, N_stage, and IC_regimen as independent prognostic factor for overall survival, while drinking and T_stage were risk factors for progression free survival. In summary, 2 cycles of platinum-based IC was effective for stage III unresectable NSCLC and adding more than 2 cycles did not offer extra survival benefits.

Adenosine 2 receptor regulates autophagy and apoptosis to alleviate ischemia reperfusion injury in type 2 diabetes via IRE-1 signaling.

PURPOSE: This study aimed to determine the effect and mechanism of action of adenosine 2 receptor (A2R) activation on myocardial ischemia reperfusion injury (MIRI) under diabetic conditions. METHODS: MIRI type 2 diabetic rats and H9C2 cardiomyocytes were treated with A2R agonist and then subjected to hypoxia for 6 h and reoxygenation for 18 h. Myocardial damage, and infarct size were determined by cardiac ultrasound. Indicators of cardiomyocyte injury, creatine kinase-MB and cardiac troponin I were detected by Enzyme Linked Immunosorbent Assay. Endoplasmic reticulum stress (ERS) was determined through measuring the expression levels of ERS related genes GRP78, p-IRE1/IRE1, and p-JNKJNK. The mechanism of A2R cardio protection in MIRI through regulating ERS induced autophagy was determined by investigating the ER resident protein IRE-1. The ER-stress inducer Tunicamycin, and the IRE-1 inhibitor STF in combination with the A2R agonist NECA were used, and the cellular responses were assessed through autophagy proteins expression Beclin-1, p62, LC3 and apoptosis. RESULTS: NECA improved left ventricular function post MIRI, limited myocardial infarct size, reduced myocardial damage, decreased cardiomyocytes apoptosis, and attenuated ERS induced autophagy through regulating the IRE-XBP1s-CHOP pathway. These actions resulted into overall protection of the myocardium against MIRI. CONCLUSION: In summary, A2R activation by NECA prior to ischemia attenuates apoptosis, reduces ERS induced autophagy and restores left ventricular function. This protective effect occurs through regulating the IRE1-XBPs-CHOP related mechanisms. NECA is thus a potential target for the treatment of MIRI in patient with type 2 diabetes.

Exosomes Derived from microRNA-27a-3p Overexpressing Mesenchymal Stem Cells Inhibit the Progression of Liver Cancer through Suppression of Golgi Membrane Protein 1.

Hepatocellular carcinoma (HCC) remains a significant health burden to date. Its early diagnosis and treatment are complicated by the lack of early diagnosis markers and multidrug resistance. microRNA regulation of HCC oncogenes are among the new diagnostic and therapeutic strategies being explored, although the mode of delivery of a therapeutic dose of the miRNA remains a challenge. In this study, we explored the use of exosomes from umbilical mesenchymal stem cells transfected with miR-27a-3p to interact with the oncogene GOLM1 in HCC and inhibit HCC progression both in vitro and in vivo. We first determined and compared the expression levels of miR-27a-3p in blood, various cell lines and tissues of HCC and their corresponding normal controls. We then employed bioinformatics analysis to determine the gene target for miR-27a-3p in HCC and later transfected upregulated miR-27a-3p in mesenchymal stem cells, and treated HCC cells with exosomes extracted from the transfected stem cells. We then created mouse models of HCC using balbc/nude mice and equally treated them with exosomes from miR-27a-3p transfected stem cells. The results showed that miR-27a-3p is downregulated in blood, cell lines, and tissues of HCC patients compared to normal controls. Exosomes from the miR-27a-3p transfected mesenchymal stem cells prevented HCC cell proliferation, invasion, and metastasis both in vitro and in vivo. Upregulation of miR-27a-3p prevented HCC through interacting with and downregulating GOLM1 as its target oncogene. In conclusion, miR-27a-3p is a potential therapeutic target for HCC acting through GOLM1.

Upregulation of the long non-coding RNA, LIPCAR promotes proliferation, migration, and metastasis of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) early diagnosis remains a challenge to date. Alpha-feto protein, though less sensitive remains widely used for both diagnosis and prognosis. Recently however, a number of molecular biomarkers have been suggested as alternatives to Alpha feto protein, especially for early diagnosis. OBJECTIVE: To determine the role of the long non-coding RNA, LIPCAR in the pathogenesis and early diagnosis of hepatocellular carcinoma. METHODS: Quantitative real-time PCR, and Fluorescence in situ hybridization assays were conducted to determine LIPCAR expression in HCC vs normal blood samples, and HCC cell lines vs normal liver cell lines. Transfection was done to upregulate LIPCAR in one HCC cell line, and used to study cell proliferation, migration, apoptosis and epithelial-mesenchymal transformation. Animal experiment was finally done to determine its effect on metastasis. RESULTS: LIPCAR was significantly upregulated in HCC blood samples and HCC cell lines compared to their respective normal ones. Its overexpression promoted hepatocellular carcinoma cell proliferation, and migration, while inhibiting apoptosis. Its overexpression also promoted epithelial-mesenchymal transformation in hepatocellular carcinoma cells, and metastasis in vivo. CONCLUSION: The study demonstrated that the lncRNA, LIPCAR is significantly upregulated in hepatocellular carcinoma patients and that its upregulation promotes HCC proliferation, migration, and metastases.

Research progress of the application of mesenchymal stem cells in chronic inflammatory systemic diseases.

Chronic inflammatory systemic diseases are the result of the body's immune imbalance, with a long course and recurring episodes. Immunosuppressants are the main treatment, but not all patients respond well to it. Being capable of both self-renewal and differentiation into multiple tissue cells and low immunogenicity, mesenchymal stem cell is a promising treatment for chronic inflammatory systemic diseases. In this article, we describe the research progress and clinical application of mesenchymal stem cells in chronic inflammatory systemic diseases and look for influencing factors and biomarkers that can predict the outcome of patient with mesenchymal stem cell transplantation.

Single-cell sequencing and its applications in bladder cancer.

Bladder cancer is the most common malignant tumour of the urinary system that is characterised by significant intra-tumoural heterogeneity. While large-scale sequencing projects have provided a preliminary understanding of tumour heterogeneity, these findings are based on the average signals obtained from the pooled populations of diverse cells. Recent advances in single-cell sequencing (SCS) technologies have been critical in this regard, opening up new ways of understanding the nuanced tumour biology by identifying distinct cellular subpopulations, dissecting the tumour microenvironment, and characterizing cellular genomic mutations. By integrating these novel insights, SCS technologies are expected to make powerful and meaningful changes to the current diagnosis and treatment of bladder cancer through the identification and usage of novel biomarkers as well as targeted therapeutics. SCS can discriminate complex heterogeneity in a large population of tumour cells and determine the key molecular properties that influence clinical outcomes. Here, we review the advances in single-cell technologies and discuss their applications in cancer research and clinical practice, with a specific focus on bladder cancer.

Serum hypomagnesemia is associated with febrile seizures in young children.

Background: Febrile seizures (FS) frequently manifest in children below 5 years of age. Although the exact etiology is still unknown, genetic predisposition, changes in neurotransmitter levels, and serum electrolyte imbalance are some of the known risk factors. This study examined the possible association between serum magnesium levels in children with FS compared to febrile children without seizures. Methods: A retrospective case-control study was conducted from February 2019 to January 2021, recruiting 230 age and gender-matched cases and controls (115 each). Extracted data were analyzed using SPSS using an independent student's t-test, Chi-square test, and Pearson's correlation analysis. Results: The mean serum magnesium levels were 0.93 ± 0.129 vs 0.97 ± 0.0961; p < 0.001, between cases and controls respectively. Similarly, hypomagnesemia (<0.85 mmol/L) was detected in 26.1% and 8.7% of the cases and controls, respectively; p < 0.001. A significant negative correlation was found between serum magnesium levels and the occurrence of febrile seizures; r = [-0.169], p < 0.05. Conclusion: Serum magnesium was significantly low in febrile children with seizures compared to those without, and hypomagnesemia was associated with the occurrence of febrile seizures. These results portray hypomagnesemia as a possible risk factor for febrile seizure, and so should be validated in future large cohort studies so that guidelines are set for proper management of these children.