Study on Predicting Clinical Stage of Patients with Bronchial Asthma Based on CT Radiomics.

Objective: To explore the value of a new model based on CT radiomics in predicting the staging of patients with bronchial asthma (BA). Methods: Patients with BA from 2018 to 2021 were retrospectively analyzed and underwent plain chest CT before treatment. According to the guidelines for the prevention and treatment of BA (2016 edition), they were divided into two groups: acute attack and non-acute attack. The images were processed as follows: using Lung Kit software for image standardization and segmentation, using AK software for image feature extraction, and using R language for data analysis and model construction (training set: test set = 7: 3). The efficacy and clinical effects of the constructed model were evaluated with ROC curve, sensitivity, specificity, calibration curve and decision curve. Results: A total of 112 patients with BA were enrolled, including 80 patients with acute attack (range: 2-86 years old, mean: 53.89±17.306 years old, males of 33) and 32 patients with non-acute attack (range: 4-79 years old, mean: 57.38±19.223 years old, males of 18). A total of 10 imaging features are finally retained and used to construct model using multi-factor logical regression method. In the training group, the AUC, sensitivity and specificity of the model was 0.881 (95% CI:0.808-0.955), 0.804 and 0.818, separately; while in the test group, it was 0.792 (95% CI:0.608-0.976), 0.792 and 0.80, respectively. Conclusion: The model constructed based on radiomics has a good effect on predicting the staging of patients with BA, which provides a new method for clinical diagnosis of staging in BA patients.

Role of lncRNAs in acute pancreatitis: pathogenesis, diagnosis, and therapy.

Acute pancreatitis (AP) is one of the most common acute abdominal diseases characterized by an injury and inflammatory disorder of the pancreas with complicated pathological mechanisms. Long non-coding RNAs (lncRNAs) have been shown to play an important role in various physiological and pathological processes in humans, and they have emerged as potential biomarkers of diagnosis and therapeutic targets in various diseases. Recently, accumulating evidence has shown significant alterations in the expression of lncRNAs, which are involved in the pathogenesis of AP, such as premature trypsinogen activation, impaired autophagy, inflammatory response, and acinar cell death. Moreover, lncRNAs can be the direct target of AP treatment and show potential as biomarkers for the diagnosis. Thus, in this review, we focus on the role of lncRNAs in the pathogenesis, diagnosis, and therapy of AP and emphasize the future directions to study lncRNAs in AP, providing new insight into understanding the cellular and molecular mechanisms of AP and seeking novel biomarkers for the diagnosis and therapeutic targets to improve clinical management in the future.

[Protective Effect of Mesenchymal Stem Cell Transplantation on Intestinal Injury in Septic Mice and Its Mechanism].

Objective: To explore the protective effect of placenta-derived mesenchymal stem cells (P-MSCs) transplantation on intestinal injury in septic mice and its mechanism. Methods: A total of 24 mice were randomly assigned to 3 groups, a sham operation group, a sepsis group that underwent cecal ligation and puncture (CLP) procedure, and a group that received CLP and P-MSCs treatment. Hereinafter, the three groups are referred to as the Sham group, the CLP group, and the CLP+P-MSCs group. For the mice in the Sham group, the abdomen was cut open and the cecum was exposed and then placed back in the abdomen. CLP was performed in the other two groups to establish the sepsis model. Mice in the Sham and the CLP groups received 0.1 mL of 0.9% NaCl injection in the tail vein 1 hour after operation, while mice in the CLP+P-MSCs group received 2×10 5 P-MSCs infusion 1 hour after operation. Intestinal and blood specimens were collected from the mice in each group 24 hours after P-MSCs transplantation. Hematoxylin and eosin (HE) staining of the intestinal tissue was performed for pathological evaluation. The serum concentrations of D-lactic acid, diamine oxidase (DAO), endotoxin, interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, IL-6, IL-10, and transforming growth factor (TGF)-ß were determined by enzyme linked immunosorbent assay (ELISA). The gene expression of the relevant inflammatory factors in the small intestinal tissue was determined by real-time fluorescence polymerase chain reaction. The expression of zonula occludens protein-1 (ZO-1) and occludin protein in the intestine was determined by Western blot, the infiltration of intestinal macrophages was determined by immunohistochemical method, and the polarization of macrophages was determined by immunofluorescence. Results: The exogenous transplantation of P-MSCs could form colonies in the injured intestines of septic mice. Compared with those of the CLP group, the intestinal injury of the CLP+P-MSCs group was significantly alleviated, the serum concentrations of D-lactic acid, DAO, endotoxin, IL-1ß, IL-6, and TNF-α were significantly decreased ( P<0.05), while the serum concentrations of IL-10 and TGF-ß were significantly increased ( P<0.05), the expression levels of IL-1 ß, TNF-α and IL-6 genes in the intestinal tissue were significantly decreased ( P<0.05), while the expression levels of IL-10 and TGF-ß genes were significantly increased ( P<0.05), and the expression of ZO-1 and occludin proteins in the intestine was also significantly increased ( P<0.05). In addition, the distribution of macrophages in the intestinal tissue of the CLP+P-MSCs group decreased significantly and the macrophages showed a tendency for M2 polarization. Conclusion: Exogenous transplantation of P-MSCs can significantly reduce inflammatory injury and improve the intestinal barrier function in septic mice with intestinal injury. Reduction in the infiltration of macrophages and promotion of the polarization of macrophages from M1 to M2 may be the mechanisms underlying the reduction of inflammation.

Triple guidance of choledochoscopy, ultrasonography, and computed tomography facilitates percutaneous catheter drainage of infected walled-off necrosis.

OBJECTIVES: Percutaneous catheter drainage (PCD) is usually performed to treat acute pancreatitis complicated by infected walled-off necrosis (WON). Insufficient drainage of infected WON may lead to a prolonged recovery process. Here, we introduce a modified PCD strategy that uses the triple guidance of choledochoscopy, ultrasonography, and computed tomography (CUC-PCD) to improve the therapeutic efficiency. METHODS: This study retrospectively analysed 73 patients with acute pancreatitis-related WON from January 2015 to January 2021. The first 38 patients were treated by ultrasonography/computed tomography-guided PCD (UC-PCD), and the next consecutive 35 patients by CUC-PCD. Perioperative data, procedural technical information, treatment outcomes, and follow-up data were collected. RESULTS: Demographic characteristics were statistically comparable between the two treatment groups (p > 0.05). After 48 h of PCD treatment, the CUC-PCD group achieved a significantly smaller size of the infected WON (p = 0.023), lower inflammatory response indexes (p = 0.020 for white blood cells, and p = 0.031 for C-reactive protein), and severity scores than the UC-PCD group (p < 0.05). Less catheter duration (p = 0.001), hospitalisation duration (p = 0.000), and global costs (p = 0.000) were observed in the CUC-PCD group compared to the UC-PCD group. There were no differences between the two groups regarding the rate of complications. CONCLUSIONS: CUC-PCD is a safe and efficient approach with potential clinical applicability for treating infected WON owing to its feasibility in placing the drainage catheter at the optimal location in real time and performing primary necrosectomy without sinus tract formation and enlargement.

N6-Methyladenosine Modification Opens a New Chapter in Circular RNA Biology.

As the most abundant internal modification in eukaryotic cells, N6-methyladenosine (m6A) in mRNA has shown widespread regulatory roles in a variety of physiological processes and disease progressions. Circular RNAs (circRNAs) are a class of covalently closed circular RNA molecules and play an essential role in the pathogenesis of various diseases. Recently, accumulating evidence has shown that m6A modification is widely existed in circRNAs and found its key biological functions in regulating circRNA metabolism, including biogenesis, translation, degradation and cellular localization. Through regulating circRNAs, studies have shown the important roles of m6A modification in circRNAs during immunity and multiple diseases, which represents a new layer of control in physiological processes and disease progressions. In this review, we focused on the roles played by m6A in circRNA metabolism, summarized the regulatory mechanisms of m6A-modified circRNAs in immunity and diseases, and discussed the current challenges to study m6A modification in circRNAs and the possible future directions, providing a comprehensive insight into understanding m6A modification of circRNAs in RNA epigenetics.

Progesterone suppresses the progression of colonic carcinoma by increasing the activity of the GADD45α/JNK/c­Jun signalling pathway.

Colorectal cancer (CRC) is the third most diagnosed cancer worldwide. Progesterone is associated with a decreased risk of CRC and leads to a favourable prognosis. However, the specific mechanism by which progesterone suppresses malignant progression remains to be elucidated. In the present study, the level of progesterone was first analysed in 77 patients with CRC, and immunohistochemistry was performed to detect the expression of progesterone receptor (PGR) in the paired specimens. The correlations between progesterone, PGR and CRC prognosis were assessed. A Cell Counting Kit­8 assay was then used to detect proliferation of the CRC cells. Flow cytometry was performed to estimate apoptosis and to evaluate the cycle of the CRC cells. A xenograft tumour model was established in nude mice to assess the role of progesterone in tumour growth. Finally, a PCR microarray was used to screen differentially expressed genes to further interpret the mechanism by which progesterone inhibits the malignant progression of CRC. It was found that low expression of progesterone and PGR were significantly associated with poor prognosis of CRC. In addition, progesterone suppressed CRC cell proliferation by arresting the cell cycle and inducing apoptosis in vitro. Moreover, the inhibitory role of progesterone in tumour growth was verified in vivo. Further investigation showed that the level of growth arrest and DNA damage­inducible protein α (GADD45α) was up­regulated by progesterone, and this was followed by the activation of the JNK pathway. Progesterone increased the activity of the JNK pathway via GADD45α to inhibit proliferation by arresting the cell cycle and inducing apoptosis, thereby suppressing the malignant progression of CRC. Therefore, it can be concluded that progesterone and PGR might act as inhibiting factors for poor prognosis of CRC.

Abdominal paracentesis drainage attenuates intestinal inflammation in rats with severe acute pancreatitis by inhibiting the HMGB1-mediated TLR4 signaling pathway.

BACKGROUND: Our previous studies confirmed that abdominal paracentesis drainage (APD) attenuates intestinal mucosal injury in rats with severe acute pancreatitis (SAP), and improves administration of enteral nutrition in patients with acute pancreatitis (AP). However, the underlying mechanisms of the beneficial effects of APD remain poorly understood. AIM: To evaluate the effect of APD on intestinal inflammation and accompanying apoptosis induced by SAP in rats, and its potential mechanisms. METHODS: SAP was induced in male adult Sprague-Dawley rats by 5% sodium taurocholate. Mild AP was induced by intraperitoneal injections of cerulein (20 µg/kg body weight, six consecutive injections). Following SAP induction, a drainage tube connected to a vacuum ball was placed into the lower right abdomen of the rats to build APD. Morphological changes, serum inflammatory mediators, serum and ascites high mobility group box protein 1 (HMGB1), intestinal barrier function indices, apoptosis and associated proteins, and toll-like receptor 4 (TLR4) signaling molecules in intestinal tissue were assessed. RESULTS: APD significantly alleviated intestinal mucosal injury induced by SAP, as demonstrated by decreased pathological scores, serum levels of D-lactate, diamine oxidase and endotoxin. APD reduced intestinal inflammation and accompanying apoptosis of mucosal cells, and normalized the expression of apoptosis-associated proteins in intestinal tissues. APD significantly suppressed activation of the intestinal TLR4 signaling pathway mediated by HMGB1, thus exerting protective effects against SAP-associated intestinal injury. CONCLUSION: APD improved intestinal barrier function, intestinal inflammatory response and accompanying mucosal cell apoptosis in SAP rats. The beneficial effects are potentially due to inhibition of HMGB1-mediated TLR4 signaling.

Abdominal paracentesis drainage ameliorates myocardial injury in severe experimental pancreatitis rats through suppressing oxidative stress.

BACKGROUND: Abdominal paracentesis drainage (APD) is a safe and effective strategy for severe acute pancreatitis (SAP) patients. However, the effects of APD treatment on SAP-associated cardiac injury remain unknown. AIM: To investigate the protective effects of APD on SAP-associated cardiac injury and the underlying mechanisms. METHODS: SAP was induced by 5% sodium taurocholate retrograde injection in Sprague-Dawley rats. APD was performed by inserting a drainage tube with a vacuum ball into the lower right abdomen of the rats immediately after SAP induction. Morphological staining, serum amylase and inflammatory mediators, serum and ascites high mobility group box (HMGB) 1, cardiac-related enzymes indexes and cardiac function, oxidative stress markers and apoptosis and associated proteins were assessed in the myocardium in SAP rats. Nicotinamide adenine dinucleotide phosphate oxidase activity and mRNA and protein expression were also examined. RESULTS: APD treatment improved cardiac morphological changes, inhibited cardiac dysfunction, decreased cardiac enzymes and reduced cardiomyocyte apoptosis, proapoptotic Bax and cleaved caspase-3 protein levels. APD significantly decreased serum levels of HMGB1, inhibited nicotinamide adenine dinucleotide phosphate oxidase expression and ultimately alleviated cardiac oxidative injury. Furthermore, the activation of cardiac nicotinamide adenine dinucleotide phosphate oxidase by pancreatitis-associated ascitic fluid intraperitoneal injection was effectively inhibited by adding anti-HMGB1 neutralizing antibody in rats with mild acute pancreatitis. CONCLUSION: APD treatment could exert cardioprotective effects on SAP-associated cardiac injury through suppressing HMGB1-mediated oxidative stress, which may be a novel mechanism behind the effectiveness of APD on SAP.