Comprehensive analysis of gene mutations and mismatch repair in Chinese colorectal cancer patients.

BACKGROUND: RAS, BRAF, and mismatch repair (MMR)/microsatellite instability (MSI) are crucial biomarkers recommended by clinical practice guidelines for colorectal cancer (CRC). However, their characteristics and influencing factors in Chinese patients have not been thoroughly described. AIM: To analyze the clinicopathological features of KRAS, NRAS, BRAF, and PIK3CA mutations and the DNA MMR status in CRC. METHODS: We enrolled 2271 Chinese CRC patients at the China-Japan Friendship Hospital. MMR proteins were tested using immunohistochemical analysis, and the KRAS/NRAS/BRAF/PIK3CA mutations were determined using quantitative polymerase chain reaction. Microsatellite status was determined using an MSI detection kit. Statistical analyses were conducted using SPSS software and logistic regression. RESULTS: The KRAS, NRAS, BRAF, and PIK3CA mutations were detected in 44.6%, 3.4%, 3.7%, and 3.9% of CRC patients, respectively. KRAS mutations were more likely to occur in patients with moderate-to-high differentiation. BRAF mutations were more likely to occur in patients with right-sided CRC, poorly differentiated, or no perineural invasion. Deficient MMR (dMMR) was detected in 7.9% of all patients and 16.8% of those with mucinous adenocarcinomas. KRAS, NRAS, BRAF, and PIK3CA mutations were detected in 29.6%, 1.1%, 8.1%, and 22.3% of patients with dMMR, respectively. The dMMR was more likely to occur in patients with a family history of CRC, aged < 50 years, right-sided CRC, poorly differentiated histology, no perineural invasion, and with carcinoma in situ, stage I, or stage II tumors. CONCLUSION: This study analyzed the molecular profiles of KRAS, NRAS, BRAF, PIK3CA, and MMR/MSI in CRC, identifying key influencing factors, with implications for clinical management of CRC.

The Effects of COVID-19 Lockdown on Glycaemic Control and Lipid Profile in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis.

The impact of the COVID-19 lockdown on glycaemic control and other metabolic parameters in patients with type 2 diabetes is still evolving. AIM: This systematic review and meta-analysis aims to examine the effects of COVID-19 lockdown on glycaemic control and lipid profile in patients with type 2 diabetes. METHODS: The PRISMA framework was the method used to conduct the systematic review and meta-analysis, and the search strategy was based on the population, intervention, control and outcome (PICO) model. The Health Sciences Research databases was accessed via EBSCO-host, and EMBASE were searched for relevant articles. Searches were conducted from inception of the databases until 17 September 2021. RESULTS: The results identified three distinct areas: glycaemic control, lipid parameters and body mass index. It was found that COVID-19 lockdown led to a significant (p < 0.01) increase in the levels of glycated haemoglobin (%) compared with pre-COVID group (gp) with a mean difference of 0.34 (95% CI: 0.30, 0.38). Eleven studies contributed to the data for glycated haemoglobin analysis with a total of 16,895 participants (post-COVID-19 lockdown gp, n = 8417; pre-COVID gp, n = 8478). The meta-analysis of fasting plasma glucose (mg/dL) also showed a significant (p < 0.05) increase in levels of post-COVID-19 lockdown gp compared with pre-COVID gp, with a mean difference of 7.19 (95% CI: 5.28, 9.10). Six studies contributed to fasting plasma glucose analysis involving a total of 2327 participants (post-COVID-19 lockdown, n = 1159; pre-COVID gp, n = 1168). The body mass index (BMI) (kg/m2) analysis also demonstrated that post-COVID-19 lockdown gp had a significantly (p < 0.05) higher BMI than the pre-COVID gp with a mean difference of 1.13 (95% CI: 0.99; 1.28), involving six studies and a total of 2363 participants (post-COVID-19 lockdown gp, n = 1186; pre-COVID gp, n = 1177). There were significantly (p < 0.05) lower levels of total cholesterol (mmol/L), triglyceride (mmol/L) and LDL cholesterol (mmol/L), and higher levels of HDL cholesterol (mg/dL) in the post-COVID-19 lockdown gp compared with pre-COVID gp, although these results were not consistent following sensitivity analysis. CONCLUSION: The findings of the systematic review and meta-analysis have demonstrated that COVID-19 lockdown resulted in a significant increase (p < 0.05) in the levels of glycated haemoglobin, fasting glucose and body mass index in patients with type 2 diabetes. In contrast, the effect of the lockdown on lipid parameters, including total cholesterol, triglycerides, LDL and HDL cholesterol was not consistent.

Effect of dietary fiber on gut barrier function, gut microbiota, short-chain fatty acids, inflammation, and clinical outcomes in critically ill patients: A systematic review and meta-analysis.

BACKGROUND: Although some studies have explored the relationships between dietary fiber (DF) supplement and gut barrier function, changes of gut microbiota, and clinical outcomes in critically ill patients, the results were not consistent. OBJECTIVE: The purpose was to explore the effect of DF on gut barrier function, gut microbiota, short-chain fatty acids (SCFAs), inflammation, and clinical outcomes in critically ill patients. METHODS: A search was performed through five databases from inception to July 12, 2021. Data were expressed as mean difference (MD) or odds ratio (OR) with CI. RESULTS: Twenty-one studies involving 2084 critically ill patients were included. There was a significant reduction in intestinal permeability, demonstrated by lactulose/rhamnose ratio (MD, -0.04; 95% CI, -0.08 to -0.00; P = 0.03) on day 8, C-reactive protein on day 14 (MD, -36.66; 95% CI, -44.40 to -28.93; P < 0.001) and duration of hospital stay (MD, -3.16; 95% CI, -5.82 to -0.49; P < 0.05) after DF supplement. There were no significant differences in SCFA levels, duration of mechanical ventilation, and mortality between two groups. However, subgroup analysis results indicated significant decreases in duration of hospital stay and risk of mortality were seen in the subgroups with a supplementary fiber dose ≥20 g/day (MD, -5.62 [95% CI, -8.04 to -3.21; P < 0.0001]; OR, 0.18 [95% CI, 0.06-0.57; P = 0.004]), as well as in the medical intensive care unit (MD, -4.77 [95% CI, -7.48 to -2.07; P < 0.01]; OR, 0.13 [95% CI, 0.03-0.65; P < 0.05]). CONCLUSIONS: DF may improve gut barrier function, modulate intestinal microbiota, decrease systemic inflammatory response, and advance clinical outcomes in critically ill patients.

Association of CT and MRI Manifestations with Pathology in Dysembryoplastic Neuroepithelial Tumors.

Objective: To investigate the CT, MRI and pathological features of dysembryoplastic neuroepithelial tumor (DNET). Methods: The CT and MRI features of six cases of pathologically confirmed DNET were retrospectively analyzed and compared with pathology. Results: All six cases of DNET were solitary, and lesion in one case was located in the right parietal lobe, one case in the right frontal lobe, one case in the cerebellar vermis, one case in the right temporo-parietal occipital lobe, one case in the left basal ganglia, and one case in the pineal gland. CT and MRI showed cystic solid tumor in all six cases, of which four showed calcification. In CT images, the cystic components appeared low-density, solid nodules, septa, and cyst walls were slightly high-density, and calcifications were high-density. In MRI images, the cystic components were hypointense on T1WI and hyperintense on T2WI, solid nodules, septa and cyst walls were iso-intense or slightly hyperintense on T1WI and T2WI sequences, and calcifications were all hypointense. On enhanced scan, the cystic components were not enhanced, and the solid nodules, septa, and cyst walls were inhomogeneously enhanced. Conclusion: The imaging manifestations of DNET are characteristic, and the combination of clinical and imaging features can greatly improve diagnostic accuracy.

Cyst(e)ine fortification in low crude protein diet improves growth performance of broilers by modulating serum metabolite profile.

This study was aimed to explore the metabolomical mechanisms for the potentially ameliorative effect of cyst(e)ine (Cys) fortification on growth performance of broilers fed low crude protein (CP) diet. A total of 432 1-d-old broilers were randomly divided into 6 groups, each of which received one of the following diets: normal-CP diet (positive control, PC), low-CP diet (negative control, NC), NC diet fortified with 0.05%, 0.1%, 0.15% or 0.2% of Cys. Samples were collected on d 42. Results showed that increasing Cys fortification quadratically elevated (P < 0.05) the accumulative growth performance and leg muscle yield of broilers fed NC diet, with 0.1% being the optimal dose. Thus, samples from PC, NC and NC plus 0.1% Cys (NCC) groups were selected for further analysis. Both dietary CP reduction and fortification of 0.1% Cys in NC diet caused complex changes (P < 0.05) in serum amino acids and some other metabolites primarily involved in lipid metabolism. Multiple lipogenesis-related pathways were regulated (P < 0.05) following Cys fortification in NC diet, which could at least partially interpret the benefit of Cys fortification in NC diet on broiler performance. In conclusion, fortifying low-CP diet with 0.1% Cys promoted the growth performance of broilers probably through modulating serum metabolite profile.

The Role of Dietary Fibre in Modulating Gut Microbiota Dysbiosis in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.

BACKGROUND: The prevalence of type 2 diabetes is on the increase worldwide, and it represents about 90% of adults who are diagnosed with diabetes. Overweight and obesity, lifestyle, genetic predisposition and gut microbiota dysbiosis have been implicated as possible risk factors in the development of type 2 diabetes. In particular, low intake of dietary fibre and consumption of foods high in fat and sugar, which are common in western lifestyle, have been reported to contribute to the depletion of specific bacterial taxa. Therefore, it is possible that intake of high dietary fibre may alter the environment in the gut and provide the needed substrate for microbial bloom. AIM: The current review is a systematic review and meta-analysis which evaluated the role of dietary fibre in modulating gut microbiota dysbiosis in patients with type 2 diabetes. METHODS: This is a systematic review and meta-analysis of randomised controlled trials which relied on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework. Electronic searches were conducted using EBSCOHost with links to Health Sciences Research Databases, EMBASE and Google Scholar. The reference lists of articles were also searched for relevant studies. Searches were conducted from date of commencement of the database to 5 August 2020. The search strategy was based on the Population, Intervention, Comparator, Outcomes, Studies (PICOS) framework and involved the use of synonyms and medical subject headings (MesH). Search terms were combined with Boolean operators (OR/AND). RESULTS: Nine studies which met the inclusion criteria were selected for the systematic review and meta-analysis, and four distinct areas were identified: the effect of dietary fibre on gut microbiota; the role of dietary fibre on short-chain fatty acids (SCFAs); glycaemic control; and adverse events. There was significant difference (p < 0.01) in the relative abundance of Bifidobacterium with a mean difference of 0.72 (95% CI, 0.56, 0.89) between the dietary fibre group compared with placebo. In relation to the meta-analysis for SCFAs, while there was significant difference (p = 0.02) between the dietary fibre group and placebo with a standardised mean difference of 0.5 (95% CI, 0.08, 0.91) regarding total SCFAs, the differences were not significant (p > 0.05) in relation to acetic acid, propionic acid and butyric acid. There was only significant improvement (p = 0.002) with respect to glycated haemoglobin with a mean difference of -0.18 (95% CI, -0.29, -0.06) between the dietary fibre group and placebo group. Differences between the two groups were not significant (p > 0.05) in relation to fasting blood glucose and homeostatic model assessment of insulin resistance (HOMA-IR). Furthermore, there were no significant differences between the two groups in subjects who reported adverse events. It is possible that the promotion of SCFA producers in greater diversity and abundance by dietary fibre in this review led to improvement in glycated haemoglobin, partly due to increased glucagon-like peptide-1 (GLP-1) production. In addition, Bifidobacterium lactis has been reported to increase glycogen synthesis, decrease expression of hepatic gluconeogenesis genes, improve translocation of glucose transport-4 and promote glucose uptake. It is also possible that the reduction in body weight of participants in the intervention group compared with control may have contributed to the observed improvement in glycated haemoglobin. CONCLUSION: This systematic review and meta-analysis have demonstrated that dietary fibre can significantly improve (p < 0.05) the relative abundance of Bifidobacterium, total SCFAs and glycated haemoglobin. However, dietary fibre did not appear to have significant effect (p > 0.05) on fasting blood glucose, HOMA-IR, acetic acid, propionic acid, butyric acid and adverse events.

Protective role of overexpressed MUC5AC against fibrosis in MHV-68-induced combined pulmonary fibrosis and emphysema mouse model.

Mucins have long been regarded to play a role as a barrier to prevent mucosal infections; however, some studies report that overexpression of mucins induces obstruction and inflammation of airways. We investigated whether the secretion of overexpressed mucin, mucin5ac (MUC5AC), could improve protection against pathogens. To examine the possible roles of mucin hypersecretion in augmenting host defense against disease-promoting muco-obstructive lung disease, a mouse model that overexpressed MUC5AC was generated. We had previously proved that murine gammaherpesvirus-68 (MHV-68) infection could induce emphysema in mice, which later developed into combined pulmonary fibrosis and emphysema (CPFE). We further explored whether increased MUC5AC secretion could provide benefits against MHV-68 induced fibrosis. We initially developed a pcDNA3.1-MUC5AC mouse model. Next, the experimental mice were randomly divided into five groups: normal control, pcDNA3.1 control, pcDNA3.1-MUC5AC, CPFE, and pcDNA3.1- MUC5AC + CPFE. Morphometric analysis of each group was performed by hematoxylin and eosin staining and Masson trichrome staining. MUC5AC levels in lung tissues were analyzed by immunohistochemical staining, real-time polymerase chain reaction, and Western blot analysis. The airway inflammation was determined by differential cell counts of bronchoalveolar lavage fluid (BALF) and measurement of cytokines and chemokines in BALF by enzyme-linked immunosorbent assay. MUC5AC hypersecretion alone was not sufficient to drive goblet cell metaplasia to induce obvious mucus plugging and airway inflammation. However, MUC5AC overexpression served as a protective barrier against MHV-68 virus infection in vivo. Infectivity of MHV-68 was decreased in the pcDNA3.1-MUC5AC + CPFE group compared with that in CPFE group. Meanwhile, a reduction of MHV-68 virus attenuated the expressions of chemokine (C-C motif) ligand 2 (CCL2), chemokine (C-X-C motif) ligand 5 (CXCL5), interleukin-13 (IL-13), and transforming growth factor-ß1 (TGF-ß1), and weakened airway inflammation and fibrosis in the pcDNA3.1-MUC5AC + CPFE group. Overexpression of MUC5AC appears to exhibit a protective role against MHV-68 infection in mice with emphysema that subsequently developed into CPFE and to further decrease airway inflammation and fibrosis induced by MHV-68 by decreasing the expressions of CCL2, CXCL5, IL-13, and TGF-ß1.

Angiomatoid Fibrous Histiocytoma Mimicking Eosinophilic Granuloma in a Pediatric Patient.

BACKGROUND: Angiomatoid fibrous histiocytoma (AFH) is a rare low-grade malignant tumor mainly occurring in soft tissues, and its incidence in the bones is extremely rare. Although most of the existing reports focus on the pathological features of AFH, only a few describe its imaging features. To our knowledge, this is the first case of AFH in the skull, and it is distinguished from eosinophilic granuloma based on imaging results. CASE DESCRIPTION: A boy aged 10 years presented with a painless mass of parietal bone after trauma. Cranial computed tomography angiography showed local bone defects near the sagittal suture of the left parietal bone and a soft tissue mass with relatively uniform density in the same area. The signals of this mass were heterogeneous in all sequences of magnetic resonance imaging and presented septal enhancement after the injection of contrast agent. The patient underwent complete resection of the mass, and the histopathological and immunohistochemical diagnosis of the mass was AFH. No complications occurred after the operation and no recurrence occurred during the follow-up. CONCLUSIONS: To our knowledge, this is the first AFH that occured in the skull, and the main imaging manifestations of AFH are bone destruction with soft tissue mass. The characteristic features of AFH are its fibrillar component that showed low signal on T2-weighted imaging and septal or peripheral enhancement, and no dead bone in the mass.

Anticancer effects of isofraxidin against A549 human lung cancer cells via the EGFR signaling pathway.

Lung cancer is the leading cause of mortality due to tumor malignancy worldwide. In recent years, the treatment of lung cancer with chemotherapy has demonstrated notable resistance and insensitivity. Therefore, it is of great importance to investigate anti­lung cancer drugs with high efficiency and low toxicity. In the present study, the effects of isofraxidin on lung cancer cells and the associated mechanisms were investigated. The results revealed that, in vivo and in vitro, isofraxidin exhibited marked inhibitory effects on the A549 lung cancer cell line. The results of Cell Counting kit­8, Transwell migration and Matrigel invasion assays, and flow cytometry to determine apoptosis, revealed that isofraxidin significantly inhibited the proliferation, migration and invasion of A549 cells, and induced the cell apoptosis. Furthermore, western blot analysis demonstrated that isofraxidin treatment led to effects on the expression of apoptosis­associated proteins, including members of the Bcl­2 protein family, and invasion­associated proteins, including matrix metallopeptidase (MMP)­2 and MMP­9, which may occur via inhibition of the expression of phosphorylated (p)­epidermal growth factor receptor, p­AKT and p­extracellular signal­regulated kinase. This regulation of protein expression may contribute to the inhibition of proliferation, migration and invasion of A549lung cancer cells by isofraxidin. In addition, despite the inhibitory effects on the A549 lung cancer cell line, the present study revealed that isofraxidin exhibited low toxicity towards BEAS­2B normal lung epithelial cells within a certain dose range (0­160 µM), indicating that isofraxidin may be employed for lung cancer treatment with hypotoxicity and fewer side effects. In conclusion, isofraxidin may be a novel candidate for anti­lung cancer chemotherapy.

[Effects of triptolide on the expression of androgen receptor in human prostate LNCaP cells and its mechanism of action].

To study the regulation of androgen receptor (AR) expression in human prostate cancer LNCaP cells by triptolide (TP) and the possible mechanism, by using qRT-PCR and Western blot, the AR mRNA and protein levels in TP treated LNCaP cells were detected, and the AR protein level in TP and NF-κB inhibitor treated LNCaP cells was also detected; a series of pGL3-AR promoter reporter gene vectors were built using restriction-free cloning method, and the vectors were employed to investigate the effects of TP on the transcriptional activity of AR promoter in LNCaP cells; the upstream proteins which may play regulatory roles were detected using western blot assay. After treated LNCaP cells with TP for 48 h, AR mRNA and protein expressions decreased with increasing TP concentration. The expression of AR target gene PART1 and prostate specific antigen (PSA) was also downregulated by TP treatment; a series of pGL3-AR promoter reporter vectors were constructed and validated by sequencing and luciferase activity; the results of dual luciferase reporter assay showed that TP downregulated AR at the transcriptional level; PI3K/AKT/NF-κB pathway which is associated with AR promoter activity was drowregulated by TP. In conclusion, our results demonstrated that the transcriptional activity of AR in LNCAP cells was downregulated by TP, and PI3K/AKT/NF-κB pathway may be involved in the regulation mechanism.