Background: Colorectal cancer (CRC) is one of the causes of cancer-related death worldwide. The aim of our study was to disclose the expression pattern and underlying molecular mechanism of circular RNA TADA2A (circTADA2A) in CRC. Methods: The levels of circTADA2A, transcriptional adaptor 2A (TADA2A), microRNA-374a-3p (miR-374a-3p) and Kruppel like factor 14 (KLF14) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Xenograft tumor assay was used to uncover the function of circTADA2A in vivo. The miRNA targets of circTADA2A were searched using circbank and starbase softwares, while DIANA TOOL was used to explore miR-374a-3p-mRNA interactions. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to validate the target relationship of circTADA2A/miR-374a-3p/KLF14 axis. Cell cycle and apoptosis were analyzed by flow cytometry. The glycolysis of CRC cells was determined by Seahorse XF e 96 Extracellular Flux Analyzer, Glucose Uptake Colorimetric Assay kit, Lactate Assay Kit II and ATP Colorimetric Assay kit. KLF14 protein level was measured by Western blot assay. Results: CircTADA2A was abnormally down-regulated in CRC tissues and cell lines. CircTADA2A overexpression impeded CRC tumor growth in vivo. MiR-374a-3p was verified as a target of circTADA2A in CRC cells, and circTADA2A inhibited the malignant potential of CRC cells through targeting miR-374a-3p. MiR-374a-3p interacted with KLF14 messenger RNA (mRNA), and miR-374a-3p deteriorated CRC through down-regulating KLF14. CircTADA2A enhanced the abundance of KLF14 through targeting miR-374a-3p in CRC cells. Conclusion: CircTADA2A functioned as a tumor suppressor in CRC to inhibit the glycolysis and cell cycle and potentiate the apoptosis of CRC cells via miR-374a-3p/KLF14 axis.

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Aicardi-Goutières syndrome (AGS) is characterized by progressive neurologic decline, cerebral calcification, and variable manifestations of autoimmunity. Seven subtypes of AGS have been defined and aberrant activation of the type I interferon system is a common theme among these conditions. We describe a 13-year-old boy who presented with an unusual constellation of psoriasis, interstitial lung disease (ILD), and pulmonary hypertension in addition to cerebral calcifications and glomerulonephritis. He was found to have late-onset AGS due to a gain-of-function mutation in IFIH1 and over-activation of the type I interferon pathway was confirmed by RNA sequencing. The majority of his clinical manifestations, including ILD, psoriasis and renal disease improved markedly after treatment with the combination of corticosteroids, cyclophosphamide, and the Janus-kinase inhibitor tofacitinib. This case extends the clinical spectrum of AGS and suggests the need for lung disease screening in patients with AGS.

Background and Purpose: Accurate prediction of functional outcome after stroke would provide evidence for reasonable post-stroke management. This study aimed to develop a machine learning-based prediction model for 6-month unfavorable functional outcome in Chinese acute ischemic stroke (AIS) patient. Methods: We collected AIS patients at National Advanced Stroke Center of Nanjing First Hospital (China) between September 2016 and March 2019. The unfavorable outcome was defined as modified Rankin Scale score (mRS) 3-6 at 6-month. We developed five machine-learning models (logistic regression, support vector machine, random forest classifier, extreme gradient boosting, and fully-connected deep neural network) and assessed the discriminative performance by the area under the receiver-operating characteristic curve. We also compared them to the Houston Intra-arterial Recanalization Therapy (HIAT) score, the Totaled Health Risks in Vascular Events (THRIVE) score, and the NADE nomogram. Results: A total of 1,735 patients were included into this study, and 541 (31.2%) of them had unfavorable outcomes. Incorporating age, National Institutes of Health Stroke Scale score at admission, premorbid mRS, fasting blood glucose, and creatinine, there were similar predictive performance between our machine-learning models, while they are significantly better than HIAT score, THRIVE score, and NADE nomogram. Conclusions: Compared with the HIAT score, the THRIVE score, and the NADE nomogram, the RFC model can improve the prediction of 6-month outcome in Chinese AIS patients.

Pyoderma gangrenosum (PG) is a rare, destructive inflammatory skin disease of which a painful nodule or pustule breaks down to form a progressively enlarging ulcer. Ulcerations associated with PG may occur after trauma or injury to the skin. The etiology has not been clearly elucidated. Our report described a PG patient with a heterozygous splice-donor-site mutation in NFKB1 (c.730+5G>A) causing the absence of exon 8 and the formation of truncated p105 (p.Asp191_Lys244delinsGlu; p105delEx8), which led to distinct symptoms of high fever and excessive inflammation in wound area after routine surgical procedures. The functional analysis showed that the variant caused reduced phosphorylation of p105 and resulted in the decreased processing of p105 to p50. We conclude that the patient's symptoms were caused by dysregulation of the NF-κB signaling pathway.

Background Subclinical atrial fibrillation (SCAF) is often asymptomatic nonetheless harmful. In patients with cardiac implantable electronic devices, we evaluated the combined performance of homocysteine and uric acid (UA) biomarkers to discriminate high‐risk patients for SCAF. Methods and Results We enrolled 1224 consecutive patients for evaluation of SCAF in patients with cardiac implantable electronic devices in Dalian, China, between January 2013 and December 2019. Clinical data and blood samples were obtained from patients selected according to the absence or presence of atrial high‐rate episodes >6 minutes. Blood samples were obtained, and homocysteine and UA biomarkers were tested in all patients to distinguish their prognostic performance for SCAF. Homocysteine and UA biomarkers were significantly different in SCAF versus no SCAF. On multivariable Cox regression analysis with potential confounders, elevated homocysteine and UA biomarkers were significantly associated with an increased risk of SCAF. A rise of 1 SD in homocysteine (5.7 μmol/L) was associated with an increased risk of SCAF in men and women regardless of their UA levels. Similarly, a 1‐SD increase in UA (91 μmol/L) was associated with an increased risk of SCAF among the patients with high levels of homocysteine in men (hazard ratio, 1.81; 95% CI, 1.43–2.30) and women (hazard ratio, 2.11; 95% CI, 1.69–2.62). The addition of homocysteine and UA to the atrial fibrillation risk factors recommended by the 2020 European Society of Cardiology Guidelines significantly improved risk discrimination for SCAF. Conclusions Homocysteine and UA biomarkers were strongly associated with SCAF. The prediction performance of the European Society of Cardiology model for SCAF was increased by the addition of the selected biomarkers. Registration URL: https://www.chictr.org.cn ; Unique identifier: Chi‐CTR200003837.

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Purpose The optimal time point for surgical resection of synchronous colorectal liver metastases (SCLMs) is still controversial. This meta-analysis evaluated the safety and long-term prognoses of simultaneous and staged resection of SCLM to provide a reference for clinical selection. Methods A systematic literature search for studies published by October 2022 was performed using PubMed, Web of Science, Embase, Scopus and Cochrane Library. The evaluated outcome parameters were total, gastrointestinal and hepatic complications, as well as perioperative mortality, intraoperative blood loss, total hospital stay, 5-year disease-free survival (DFS) and 5-year overall survival (OS). Results This meta-analysis included 22 nonrandomised and one randomised study comprising 4862 patients. The patients undergoing simultaneous resection of SCLM had similar total (OR = 0.88, 95% CI [0.66–1.19], P = 0.409), gastrointestinal (OR = 1.19, 95% CI [0.89–1.59], P = 0.241) and hepatic (OR = 1.04, 95% CI [0.83–1.31], P = 0.734) complications, as well as perioperative mortality (OR = 1.79, 95% CI [0.88–3.64], P = 0.108), 5-year DFS (HR = 1.26, 95% CI [0.96–1.66], P = 0.098) and 5-year OS (HR = 1.13, 95% CI [0.95–1.34], P = 0.164). Lower intraoperative blood loss (SMD = − 0.39, 95% CI [− 0.60 to − 0.18], P < 0.001) and shorter total hospital stay (WMD = − 5.43, 95% CI [− 7.29 to − 3.58], P < 0.001) were observed in the simultaneous-resection group versus the staged group. Conclusions Simultaneous resection is safe and effective for SCLM patients. The long-term prognosis is equivalent to that of the traditional staged resection. Correct selection of resectable SCLM patients for the simultaneous resection of the primary tumour and liver metastases can be the first choice. Owing to the potential heterogeneity, more RCTs should be included to verify our conclusions.