Pomegranate (Punica granatum L.) peel extract ameliorates metabolic syndrome risk factors in patients with non-alcoholic fatty liver disease: a randomized double-blind clinical trial.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is a metabolic syndrome (MS)-related liver disorder that has an increasing prevalence. Thus, the aim of our study is to evaluate the effects of pomegranate peel extract (PP) supplementation on hepatic status and metabolic syndrome risk factors. METHODS: In phase one, the hydro-alcoholic extraction of the peel of 750 kg of pomegranate (Punica granatum L.) was performed by the soaking method. Then, in phase two, NAFLD patients received 1500 mg of placebo (n = 37) or pomegranate peel capsules (n = 39) with a 500-kcal deficit diet for 8 weeks. Gastrointestinal intolerance, dietary intake, lipid and glycemic profiles, systolic and diastolic blood pressure, body composition, insulin resistance indexes, and elastography-evaluated NAFLD changes were followed. RESULTS: The mean age of participants was 43.1 ± 8.6 years (51.3% female). Following the intervention, the mean body weight (mean changes: -5.10 ± 2.30 kg), waist circumference (-7.57 ± 2.97 cm), body mass index (-1.82 ± 0.85 kg/m2), body fat index (-1.49 ± 0.86), and trunk fat (- 3.93 ± 3.07%), systolic (-0.63 ± 0.29 cmHg) and diastolic (-0.39 ± 0.19 cmHg) blood pressure, total cholesterol (-10.51 ± 0.77 mg/dl), triglyceride (-16.02 ± 1.7 mg/dl), low-density lipoprotein cholesterol (-9.33 ± 6.66 mg/dl; all P < 0.001), fat free mass (- 0.92 ± 0.90 kg; P < 0.003), and fasting blood sugar (-5.28 ± 1.36 mg/dl; P = 0.02) decreased significantly in PP in contrast to the placebo group in the raw model and when adjusted for confounders. Also, high-density lipoprotein cholesterol (5.10 ± 0.36 mg/dl), liver steatosis and stiffness (- 0.30 ± 0.17 and - 0.72 ± 0.35 kPa, respectively, all P < 0.001) improved in the PP group. However, fasting insulin (P = 0.81) and homeostatic model assessment for insulin resistance (HOMA-IR) (P = 0.93) were not significantly different when comparing two groups during the study in the raw and even adjusted models. CONCLUSION: In conclusion, 1500 mg pomegranate peel extract along with a weight-loss diet improved metabolic syndrome risk factors and reduced hepatic steatosis in patients with NAFLD after 8 weeks.

Colorectal Cancer in North-Eastern Iran: a retrospective, comparative study of early-onset and late-onset cases based on data from the Iranian hereditary colorectal cancer registry.

BACKGROUND: The incidence rate of colorectal cancer (CRC) is increasing among patients below 50 years of age. The reason for this is unclear, but could have to do with the fact that indicative variables, such as tumour location, gender preference and genetic preponderance have not been followed up in a consistent mann er. The current study was primarily conducted to improve the hereditary CRC screening programme by assessing the demographic and clinicopathological characteristics of early-onset CRC compared to late-onset CRC in northeast Iran. METHODS: This retrospective study, carried out over a three-year follow-up period (2014-2017), included 562 consecutive CRCs diagnosed in three Mashhad city hospital laboratories in north-eastern Iran. We applied comparative analysis of pathological and hereditary features together with information on the presence of mismatch repair (MMR) gene deficiency with respect to recovery versus mortality. Patients with mutations resulting in absence of the MMR gene MLH1 protein product and normal BRAF status were considered to be at high risk of Lynch syndrome (LS). Analyses using R studio software were performed on early-onset CRC (n = 222) and late-onset CRC (n = 340), corresponding to patients ≤50 years of age and patients > 50 years. RESULTS: From an age-of-onset point of view, the distribution between the genders differed with females showing a higher proportion of early-onset CRC than men (56% vs. 44%), while the late-onset CRC disparity was less pronounced (48% vs. 52%). The mean age of all participants was 55.6 ± 14.8 years, with 40.3 ± 7.3 years for early-onset CRC and 65.1 ± 9.3 years for late-onset CRC. With respect to anatomical tumour location (distal, rectal and proximal), the frequencies were 61, 28 and 11%, respectively, but the variation did not reach statistical significance. However, there was a dramatic difference with regard to the history of CRC in second-degree relatives between two age categories, with much higher numbers of family-related CRCs in the early-onset group. Expression of the MLH1 and PMS2 genes were significantly different between recovered and deceased, while this finding was not observed with regard to the MSH6 and the MSH2 genes. Mortality was significantly higher in those at high risk of LS. CONCLUSION: The variation of demographic, pathological and genetic characteristics between early-onset and late-onset CRC emphasizes the need for a well-defined algorithm to identify high-risk patients.

The predictive role of parathyroid hormone for non-alcoholic fatty liver disease based on invasive and non-invasive findings in candidates of bariatric surgery.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH) and hepatic fibrosis are the most detrimental hepatic abnormalities associated with increased body weight with devastating clinical outcomes. Therefore, there is a substantial necessity for efficient management strategies, including significant weight reduction. Bariatric surgery has been used as a therapeutic approach in a selected obese patient with NAFLD/NASH and other cardiometabolic comorbidities. PURPOSE: The study is focused on the predictive role of PTH with the indices of hepatic steatosis/NAFLD and NASH based on liver biopsy, elastography, and sonography in morbidly obese patients. METHODS: Ninety patients with BMI between 35 and 40 kg/m2 with more than two comorbidities who referred to Imam Reza outpatient clinic from December 2016 to September 2017 were recruited and underwent initial assessments, including demographic profiles, psychological assessment, anthropometric measurements, hepatic biopsy, and basic laboratory tests. Liver stiffness was evaluated using two-dimensional shear wave elastography (2D-SWE) at least two weeks before liver biopsy. The histological analysis of the liver was performed using biopsy samples which obtained from left hepatic lobe during bariatric surgery under direct surgeon observation using a 16-gauge Tru-cut needle. The study was approved by the ethical committee (IR.MUMS.fm.REC.1396.312). RESULTS: The level of PTH was significantly high in patients with positive histology for hepatic fibrosis, steatosis, and NASH/NAFLD compared to patients with negative histology (p = 0.005, p = 0.009, and p = 0.013, respectively). Also, patients with liver fibrosis confirmed by elastography had significantly higher serum PTH concentration than patients without fibrosis (p = 0.011). PTH was also positively correlated with hepatic fibrosis, NASH, and steatosis (p = 0.007, p = 0.012, p = 0.023, respectively). CONCLUSION: High levels of PTH was significantly associated with histological indices of (hepatic fibrosis, steatosis, NAFLD and NASH) and elasticity indices. Therefore, it is imperative to assess for high levels of PTH in the morbidly obese population pre-and post-bariatric surgery. However, for a more robust and comprehensive assessment, a randomized controlled trial is needed. The study was conducted in accordance with the practice guidance in the diagnosis and management of NAFLD from the American association for the study of liver disease (AASLD) 2018. LEVEL III: Evidence obtained from well-designed cohort or case-control analytic studies.

Characteristics of gastric precancerous conditions and Helicobacter pylori infection among dyspeptic patients in north-eastern Iran: is endoscopic biopsy and histopathological assessment necessary?

BACKGROUND: Early detection and appropriate treatment of precancerous, mucosal changes could significantly decrease the prevalence of life-threatening gastric cancer. Biopsy of the normal-appearing mucosa to detect Helicobacter pylori and these conditions is not routinely obtained. This study assesses the prevalence and characteristics of H. pylori infection and precancerous conditions in a group of patients suffering from chronic dyspepsia who were subjected to gastric endoscopy and biopsy mapping. METHODS: This cross-sectional study included dyspeptic patients, not previously treated for H. pylori, undergoing esophagogastroduodenoscopy (EGD) with their gastric endoscopic biopsies obtained for examination for evidence of H. pylori infection and precancerous conditions. Demographic and clinical data on the gender, smoking, opium addiction, alcohol consumption, medication with aspirin, corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs) and family history of cancer were collected by interviewing the patients and evaluating their health records. The cohort examined consisted of 585 patients with a mean (SD) age of 48.0 (14.46) years, 397 (67.9%) of whom were women. RESULTS: H. pylori infection was identified in 469 patients (80.2%) with the highest prevalence (84.2%) in those aged 40-60 years. Opium addiction correlated with a higher a H. pylori infection rate, while alcohol consumption was associated with a lower rate by Odds Ratio 1.98 (95% CI 1.11-3.52) and 0.49 (95% CI 0.26-0.92), respectively. The prevalence of intestinal metaplasia, gastric atrophy and gastric dysplasia was 15.2, 12.6 and 7.9%, respectively. Increased age, positive H. pylori infection, endoscopic abnormal findings and opium addiction showed a statistically significant association with all precancerous conditions, while NSAID consumption was negatively associated with precancerous conditions. For 121 patients (20.7% of all), the EGD examination revealed normal gastric mucosa, however, for more than half (68/121, 56.2%) of these patients, the histological evaluation showed H. pylori infection, and also signs of atrophic mucosa, intestinal metaplasia and dysplasia in 1.7, 4.1 and 1.7%, respectively. CONCLUSION: EGD with gastric biopsy mapping should be performed even in the presence of normal-appearing mucosa, especially in dyspeptic patients older than 40 years with opium addiction in north-eastern Iran. Owing to the high prevalence of precancerous conditions and H. pylori infection among patients with dyspepsia in parts of Iran, large-scale national screening in this country should be beneficial.

Demographic and clinical characteristics of severe Covid-19 infections: a cross-sectional study from Mashhad University of Medical Sciences, Iran.

BACKGROUND: Coronavirus Disease 2019 (Covid-19) is expanding worldwide. The characteristics of this infection in patients varies from country to country. To move forward, clinical data on infected patients are needed. Here, we report a comparison between fatalities and recovery of patients with severe Covid-19, based on demographic and clinical characteristics. METHODS: Between 5 March and 12 May 2020 in Mashhad, Iran, 1278 of 4000 suspected Covid-19 patients were confirmed positive by real-time reverse-transcriptase-polymerase-chain-reaction assay of upper respiratory specimens. We compared the demographic, exposure history and clinical symptoms of 925 survivors and 353 fatal cases with confirmed disease. RESULTS: Mean (SD) age for all confirmed patients was 56.9 (18.7) years, 67.1 (15.9) years in fatal cases and 53.0 (18.3) years in survivors. Multivariate logistic regression analysis showed that the outcome of patients was associated with age (odds ratio = 1.049, P = 0.0001, 95% CI = 1.040-1.057). Despite a high burden of Covid-19 infections in the 30-39 and 40-49 year age groups, most of these (89.6 and 87.2%, respectively) recovered. The median (IQR) duration of hospitalization was 9.0 (6.0-14.0) days. The most prevalent co-morbidities were cardiovascular disorders (21%) and diabetes (16.3%). Dyspnoea (72.7%), cough (68.1%) and fever (63.8%) were the most frequent clinical symptoms. Healthcare workers, of whom two (3%) died, comprised 5.2% of infected cases. Combination antiviral and antibiotic therapy was used in 43.0% of cases. CONCLUSIONS: The characteristics of severe Covid-19 varied substantially between fatal cases and survivors, with diabetes and cardiovascular disorders the most prevalent co-morbidities. In contrast to other studies, there were a higher number of fatalities in younger patients in our setting.

Investigating the association between rs6983267 polymorphism and susceptibility to gastrointestinal cancers in Iranian population.

Genome-wide association studies have revealed that some single nucleotide polymorphisms at 8q24, such as rs6983267, might be effective in susceptibility to various cancers in different populations. Therefore, rs6983267 might be useful as a marker for multiple cancers. In this study, we considered a population, including 478 gastrointestinal cancer cases from the Iranian population, to investigate the association between rs6983267 and susceptibility to gastrointestinal cancers. The samples were genotyped using the TaqMan real-time PCR method while 10% of them were also confirmed by sequencing. Higher frequency of G allele was associated with higher grades of tumors in esophageal cancer and the tumors located in the lower portion of the esophagus (OR 3.56; 95% CI 1.13-11.24; P = 0.03) and cardia (OR 5.24; 95% CI 1.26-21.83; P = 0.02), which both locations are involved in esophageal adenocarcinomas with poor prognosis. The results indicated that in the male subgroup, the rs6983267 GG genotype significantly enhanced the gastric cancer susceptibility (OR 4.76; 95% CI 1.57-14.45; P = 0.01). GG genotype also increased the risk of intestinal-type gastric cancer, located in non-cardia (OR 4.62; 95% CI 1.25-17.04; P = 0.02). Moreover, gastric cancer cases and controls with a family history of gastrointestinal tumors were mostly genotyped with the G allele (OR 3.61; 95% CI = 1.09-12.01; P = 0.04). There were no remarkable associations between rs6983267 and susceptibility to esophageal and colon cancers in the Iranian population. However, different genotypes of rs6983267 had significant correlations with tumor grade, cancer type, and family history of gastrointestinal cancers. Further investigations in a larger population and other ethnicities are required to confirm these results.

Protective effects of propolis on hepatic steatosis and fibrosis among patients with nonalcoholic fatty liver disease (NAFLD) evaluated by real-time two-dimensional shear wave elastography: A randomized clinical trial.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, while no drugs have been approved for its treatment. The pieces of evidence indicate that propolis as a novel anti-inflammatory agent might be a promising candidate to treat NAFLD. We aimed to evaluate the efficacy of propolis on hepatic steatosis and fibrosis in patients with NAFLD. This randomized clinical trial was conducted on 54 patients with NAFLD. Patients were randomly assigned to receive propolis tablets at a dose of 250 mg twice daily for 4 months or placebo. The improvement in hepatic steatosis and fibrosis was evaluated using two-dimensional shear wave elastography. Improvement in the hepatic steatosis was significantly higher in the propolis group than the placebo group, even after adjustment for baseline value and changes in weight, energy intake, and physical activity (odds ratio [OR]: 5.67; 95% confidence intervals [CI]: 1.41-22.8; p = .014). A significant reduction was observed on the liver stiffness in the propolis group (-0.65 ± 0.56 kPa; p = .001), whereas it increased in the placebo group (0.27 ± 0.59 kPa; p = .037). Also, the intake of propolis significantly decreased high-sensitivity C-reactive protein (hs-CRP) levels compared with the placebo group (-0.371; 95%CI: -0.582 to -0.16 mg/L; p = .01). Changes in serum levels of fasting blood sugar, alanine aminotransferase, aspartate aminotransferase, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, cholesterol, and triglyceride did not differ significantly between the two groups (p > .05). There was no significant improvement in insulin resistance in both groups (p > .05). Propolis seems to have protective effects on hepatic steatosis and fibrosis and to reduce the serum levels of hs-CRP in patients with NAFLD.

Promoter methylation, transcription, and retrotransposition of LINE-1 in colorectal adenomas and adenocarcinomas.

BACKGROUND: The methylation of the CpG islands of the LINE-1 promoter is a tight control mechanism on the function of mobile elements. However, simultaneous quantification of promoter methylation and transcription of LINE-1 has not been performed in progressive stages of colorectal cancer. In addition, the insertion of mobile elements in the genome of advanced adenoma stage, a precancerous stage before colorectal carcinoma has not been emphasized. In this study, we quantify promoter methylation and transcripts of LINE-1 in three stages of colorectal non-advanced adenoma, advanced adenoma, and adenocarcinoma. In addition, we analyze the insertion of LINE-1, Alu, and SVA elements in the genome of patient tumors with colorectal advanced adenomas. METHODS: LINE-1 hypomethylation status was evaluated by absolute quantitative analysis of methylated alleles (AQAMA) assay. To quantify the level of transcripts for LINE-1, quantitative RT-PCR was performed. To find mobile element insertions, the advanced adenoma tissue samples were subjected to whole genome sequencing and MELT analysis. RESULTS: We found that the LINE-1 promoter methylation in advanced adenoma and adenocarcinoma was significantly lower than that in non-advanced adenomas. Accordingly, the copy number of LINE-1 transcripts in advanced adenoma was significantly higher than that in non-advanced adenomas, and in adenocarcinomas was significantly higher than that in the advanced adenomas. Whole-genome sequencing analysis of colorectal advanced adenomas revealed that at this stage polymorphic insertions of LINE-1, Alu, and SVA comprise approximately 16%, 51%, and 74% of total insertions, respectively. CONCLUSIONS: Our correlative analysis showing a decreased methylation of LINE-1 promoter accompanied by the higher level of LINE-1 transcription, and polymorphic genomic insertions in advanced adenoma, suggests that the early and advanced polyp stages may host very important pathogenic processes concluding to cancer.

Expression profile analysis of two antisense lncRNAs to improve prognosis prediction of colorectal adenocarcinoma.

BACKGROUND: Long noncoding RNAs (lncRNAs) are involved in different pathogenesis pathways including cancer pathogenesis. The adenoma-carcinoma pathway in colorectal cancer may involve the aberrant and variable gene expression of regulatory RNAs. This study was conducted to analyse the expression and prognosis prediction ability of two natural antisense transcripts, protein kinase C theta antisense RNA 1 (PRKCQ-AS1), and special AT-rich sequence binding protein 1 antisense RNA 1 (SATB1-AS1) in colorectal low-grade adenoma, advanced adenoma, and adenocarcinomas. METHODS: In this study, from two RNA-seq analyses of CCAT1-ko cells and colorectal carcinoma biopsies having diminished and increased levels of CCAT1 transcription, respectively, we nominated two antisense lncRNAs of PRKCQ-AS1 and SATB1-AS1. Samples from colorectal low-grade adenomas, advanced adenomas, adenocarcinomas, and adjacent tissue were subjected to RT-qPCR to determine the expression of PRKCQ-AS1, SATB1-AS1 along with colon cancer-associated transcript 1 (CCAT1) and cMYC. In addition, we used different bioinformatics analyses and webservers (including GEPIA 2, TCGA, and CancerMine) to elucidate the prognosis prediction value, the expression correlation of sense-antisense pair of genes, and the expression profile of these antisense transcripts at the presence or absence of mutations in the driver genes, or the corresponding sense genes. RESULTS: PRKCQ-AS1 showed a wide range of expression levels in colorectal adenoma, advanced adenoma, and adenocarcinoma. Upregulation of PRKCQ-AS1 was related to a significant decrease in survival of colorectal cancer (CRC) patients. The expression levels of PRKCQ-AS1 and PRKCQ were strong and significantly concordant in normal and cancerous colorectal tissues. While SATB1-AS1 showed a wide range of expression in colorectal adenoma, advanced adenoma, and adenocarcinoma as well, its expression was not related to a decrease in survival of CRC patients. The expression levels of SATB1-AS1 and SATB1 (the sense gene) were not strong in normal colorectal tissues. In addition, where SATB1 gene was mutated, the expression of SATB1-AS1 was significantly downregulated. CONCLUSIONS: We found the expression of PRKCQ-AS1 and SATB1-AS1 at a given stage of CRC very variable, and not all biopsy samples showed the increased expression of these antisense transcripts. PRKCQ-AS1 in contrast to SATB1-AS1 showed a significant prognostic value. Since a significantly concordant expression was observed for SATB1-AS1 and SATB1 in only cancerous, and for PRKCQ-AS1 and PRKCQ in both normal and cancerous colorectal tissues, it can be concluded that common mechanisms may regulate the expression of these sense and antisense genes.

G-Protein Signaling Modulator 2 as a Potential Biomarker in Colorectal Cancer: Integrative Analysis Using Genetic Profiling and Pan-Cancer Studies.

Colorectal cancer (CRC) imposes a significant healthcare burden globally, prompting the quest for innovative biomarkers to enhance diagnostic and therapeutic strategies. This study investigates the G-protein signaling modulator (GPSM) family across several cancers and presents a comprehensive pan-cancer analysis of the GPSM2 gene across several gastrointestinal (GI) cancers. Leveraging bioinformatics methodologies, we investigated GPSM2 expression patterns, protein interactions, functional enrichments, prognostic implications, genetic alterations, and immune infiltration associations. Furthermore, the expression of the GPSM2 gene was analyzed using real-time analysis. Our findings reveal a consistent upregulation of GPSM2 expression in all GI cancer datasets analyzed, suggesting its potential as a universal biomarker in GI cancers. Functional enrichment analysis underscores the involvement of GPSM2 in vital pathways, indicating its role in tumor progression. The prognostic assessment indicates that elevated GPSM2 expression correlates with adverse overall and disease-free survival outcomes across multiple GI cancer types. Genetic alteration analysis highlights the prevalence of mutations, particularly missense mutations, in GPSM2. Furthermore, significant correlations between GPSM2 expression and immune cell infiltration are observed, suggesting its involvement in tumor immune evasion mechanisms. Collectively, our study underscores the multifaceted role of GPSM2 in GI cancers, particularly in CRC, emphasizing its potential as a promising biomarker for prognosis and therapeutic targeting. Further functional investigations are warranted to elucidate its clinical utility and therapeutic implications in CRC management.

PTEN hamartoma tumour syndrome: case report based on data from the Iranian hereditary colorectal cancer registry and literature review.

BACKGROUND: PTEN hamartoma tumour syndrome (PHTS) is a rare hereditary disorder caused by germline pathogenic mutations in the PTEN gene. This study presents a case of PHTS referred for genetic evaluation due to multiple polyps in the rectosigmoid area, and provides a literature review of PHTS case reports published between March 2010 and March 2022. CASE PRESENTATION: A 39-year-old Iranian female with a family history of gastric cancer in a first-degree relative presented with minimal bright red blood per rectum and resistant dyspepsia. Colonoscopy revealed the presence of over 20 polyps in the rectosigmoid area, while the rest of the colon appeared normal. Further upper endoscopy showed multiple small polyps in the stomach and duodenum, leading to a referral for genetic evaluation of hereditary colorectal polyposis. Whole-exome sequencing led to a PHTS diagnosis, even though the patient displayed no clinical or skin symptoms of the condition. Further screenings identified early-stage breast cancer and benign thyroid nodules through mammography and thyroid ultrasound. METHOD AND RESULTS OF LITERATURE REVIEW: A search of PubMed using the search terms "Hamartoma syndrome, Multiple" [Mesh] AND "case report" OR "case series" yielded 43 case reports, predominantly in women with a median age of 39 years. The literature suggests that patients with PHTS often have a family history of breast, thyroid and endometrial neoplasms along with pathogenic variants in the PTEN/MMAC1 gene. Gastrointestinal polyps are one of the most common signs reported in the literature, and the presence of acral keratosis, trichilemmomas and mucocutaneous papillomas are pathognomonic characteristics of PHTS. CONCLUSION: When a patient presents with more than 20 rectosigmoid polyps, PHTS should be considered. In such cases, it is recommended to conduct further investigations to identify other potential manifestations and the phenotype of PHTS. Women with PHTS should undergo annual mammography and magnetic resonance testing for breast cancer screening from the age of 30, in addition to annual transvaginal ultrasounds and blind suction endometrial biopsies.

Impact of Various Risk Factors on the Positive Fecal Immunochemical Test for Colorectal Cancer in the Iranian Population.

Background: Colorectal cancer (CRC) is the most prevalent cancer with high mortality worldwide. We aimed to evaluate the incidence of CRC based on the positive fecal immunochemical test (FIT) result in the Iranian population. Methods: The present study was conducted on the health assessment data recorded in the SINA (Integrated Health Information System) in 2018 and 2019 from individuals who had participated in the national program, including asymptomatic people aged 50-69 years or had risk factors of CRC such as family or past personal history of CRC as well as symptomatic individuals, for the early detection and prevention of CRC in Mashhad, Iran. Results: The study participants included 140,463 eligible individuals, of whom 8258 (5.88%) and 145 (2.21%) were positive for FIT and diagnosed with colon cancer, respectively. Unfortunately, only 654 people had undergone colonoscopy. Our results indicated that age, fast food intake (≥two units per day), family history of CRC in first or second-degree relatives, some gastrointestinal diseases such as inflammatory bowel disease (IBD) and CRC, as well as bleeding per anus, constipation, abdominal cramp, and losing body weight were associated with increased risk of positive FIT. However, some other factors, including having a hard job, physical activity, and Iranian nationality (compared to non-Iranians), were associated with a low risk of positive FIT screening tests for CRC. Conclusion: A high number of high-risk persons in Mashhad were positive for the FIT test in 2018-2019, and many of them were diagnosed with CRC, according to the colonoscopy results. Therefore, screening is highly recommended as the first step in the early detection of CRC.

Impact of gastric bypass surgery on the liver fibrosis of patients with extreme obesity and nonalcoholic fatty liver disease in 30-month follow-up.

Roux-en-Y gastric bypass surgery (RYGB) has shown efficacy in weight loss, but its role in liver fibrosis remains unknown and contentious. The present study aimed to investigate the effect of RYGB on liver fibrosis measured by non-invasive methods and assess the impact of weight loss on hepatic fibrosis in the midterm follow-up after RYGB. This longitudinal study was conducted on patients with extreme obesity, and NAFLD referred for RYGB during 2016-2018 for 3 years after their surgery. A liver biopsy was performed intraoperatively. The patient demographics, anthropometrical parameters, biochemical variables, and Liver stiffness (LS) using two-dimensional shear-wave elastography were recorded and analyzed before and in short-term and midterm follow-ups. Fifty-four patients were included with a mean age of 40.3 years; 83.3% were women. At a median follow-up of 30 months (range: 24-36 months), the excessive body mass index loss of the patients was 78.1% and, a significant reduction was seen in LS measurement. Two patients (4%) had worsening showed in the fibrosis stage, 28 (54%) no change, and 24 (42%) showed improvement, 30 months after the surgery. Moreover, the liver fibrosis stage regressed to F0 in 91% of the patients. Hepatic fibrosis resolved in the midterm follow-up in some patients whose fibrosis had progressed and deteriorated in the short-term follow-up. In addition, Liver enzymes were decreased. RYGB seems to be an effective procedure for sustained weight loss and improved liver fibrosis in EO and NAFLD patients in midterm follow-up.

Differentiating benign and malignant thyroid nodules: A cross-sectional study on the comparison of diagnostic value of ultrasound elastography and fine needle aspiration biopsy.

Background and Aim: This study examines the comparison of ultrasound elastography and fine needle aspiration (FNA) in diagnosing thyroid cancers and investigates the use of elastography as the initial diagnostic test of thyroid cancers to avoid the need for invasive diagnostic tests. Methods: In this study, 28 patients with 48 thyroid nodules (TNs) who were candidates for FNA or surgery were examined within a period of 18 months. Cut-off and subsequently sensitivity and specificity for elastography results, compared to pathology results as the gold standard, were calculated using the receiver operating characteristic curve (ROC). Results: Based on ROC, the cut-off point differentiating the tissue stiffness between benign and malignant TNs was 25.400 kilopascal (kPa) (sensitivity of 90.9% and specificity of 78.4%). It was observed that age affects the tissue stiffness; therefore, the cut-off was defined as 65.625 kpa for age groups under 50 years old (sensitivity of 100% and specificity of 100%) and 25.400 kpa for the age group above 50 years old (sensitivity of 88.9% and specificity of 70.4%). Conclusion: Based on the high sensitivity and specificity of shear wave elastography in the differentiation of benign and malignant TNs, it can be employed as a stand-alone or in combination with other diagnostic techniques to reduce the need for inessential surgical operations. However, future studies or developments are needed on this promising diagnostic technique.

The Prognostic Value of ASPHD1 and ZBTB12 in Colorectal Cancer: A Machine Learning-Based Integrated Bioinformatics Approach.

Introduction: Colorectal cancer (CRC) is a common cancer associated with poor outcomes, underscoring a need for the identification of novel prognostic and therapeutic targets to improve outcomes. This study aimed to identify genetic variants and differentially expressed genes (DEGs) using genome-wide DNA and RNA sequencing followed by validation in a large cohort of patients with CRC. Methods: Whole genome and gene expression profiling were used to identify DEGs and genetic alterations in 146 patients with CRC. Gene Ontology, Reactom, GSEA, and Human Disease Ontology were employed to study the biological process and pathways involved in CRC. Survival analysis on dysregulated genes in patients with CRC was conducted using Cox regression and Kaplan-Meier analysis. The STRING database was used to construct a protein-protein interaction (PPI) network. Moreover, candidate genes were subjected to ML-based analysis and the Receiver operating characteristic (ROC) curve. Subsequently, the expression of the identified genes was evaluated by Real-time PCR (RT-PCR) in another cohort of 64 patients with CRC. Gene variants affecting the regulation of candidate gene expressions were further validated followed by Whole Exome Sequencing (WES) in 15 patients with CRC. Results: A total of 3576 DEGs in the early stages of CRC and 2985 DEGs in the advanced stages of CRC were identified. ASPHD1 and ZBTB12 genes were identified as potential prognostic markers. Moreover, the combination of ASPHD and ZBTB12 genes was sensitive, and the two were considered specific markers, with an area under the curve (AUC) of 0.934, 1.00, and 0.986, respectively. The expression levels of these two genes were higher in patients with CRC. Moreover, our data identified two novel genetic variants-the rs925939730 variant in ASPHD1 and the rs1428982750 variant in ZBTB1-as being potentially involved in the regulation of gene expression. Conclusions: Our findings provide a proof of concept for the prognostic values of two novel genes-ASPHD1 and ZBTB12-and their associated variants (rs925939730 and rs1428982750) in CRC, supporting further functional analyses to evaluate the value of emerging biomarkers in colorectal cancer.

Clinical Significance of TRIM44 Expression in Patients with Gastric Cancer.

BACKGROUND: Despite the tremendous efforts in finding a valuable markers for risk stratifying gastric cancer (GC) patients; still, management of this cancer faces multiple obstacles. Given this, we designed a study to explore the possible relationship between the tripartite motif-containing 44 (TRIM44) gene expression, and the outcome of the GC patients. METHODS: The real-time quantitative PCR method was used to evaluate the mRNA expression level of TRIM44, and ß-catenin in fresh primary tumor and adjacent normal tissues collected from 40 GC patients. The Pearson's correlation test, Kaplan-Meier method, and Cox proportional-hazards regression were performed to examine the association of TRIM44 expression with some clinicopathological data and the patients' overall survival (OS). RESULTS: The expression level of both TRIM44 and ß-catenin was remarkably higher in GC tissues than in normal tissues (Fold change=1.71, p=0.004). In subgroup analysis based on the TRIM44 expression, pateints with high TRIM44 expression level exhibited poorer overall survival (HR = 1.46, 95% CI: 1.07-1.98, p=0.016). More strikingly, a positive correlation was also found between the expression of TRIM44 and ß-catenin in GC, indicating that TRIM44 might exert its oncogenic activities probably through the ß-catenin axis. CONCLUSION: This study highlighted the potent value of TRIM44 as an independent prognostic factor in gastric cancer and shed light on the probable interplay between this tripartite motif-containing protein and ß-catenin. However, further investigations, especially with a larger sample size, are required to study the effect of TRIM44 in GC more precisely.

Decreased expression of TRIM3 gene predicts a poor prognosis in gastric cancer.

BACKGROUND/AIMS: Tripartite motif-containing 3 (TRIM3) is a member of the TRIM protein family which is known to be involved in development of numerous tumor types. However, the prognostic role of TRIM3 in gastric cancer (GC) remained to be clarified. The aim of this study was to evaluate the expression pattern and prognostic significance of TRIM3 gene and its relationship with ß-catenin, CyclinD, and BCL2 expression in patients with GC. METHODS: A total of 40 fresh primary gastric cancer tumors and their matched adjacent noncancerous tissues were selected from the First Affiliated Hospital of Mashhad University. Real-time quantitative RT-PCR was performed to evaluate differences in TRIM3 expression in GC and normal tissues. The correlation between TRIM3 expression level and patients' overall survival, some clinicopathological variables, and ß-catenin, CyclinD, and BCL-2 genes expression level were also studied. Moreover, patients were divided in two groups according to the TRIM3 expression levels: low and high. RESULTS: Compared to noncancerous tissues, TRIM3 expression in GC tissues was significantly increased (fold change = 1.58). Kaplan-Meier survival analysis revealed a significant difference of patient survival according to TRIM3 expression status (P = 0.012). Low TRIM3 expression was associated with shorter overall survival and was an independent predictor for poor prognosis in GC patients (HR, 1.25; 95%CI, 1.02-1.60; P = 0.045). Expression of TRIM3 was negatively correlated with expression of ß-catenin, BCL-2, and CyclinD as genes for proliferation, apoptosis, and the cell cycle in GC patients. CONCLUSIONS: This study demonstrates that decreased level of TRIM3 mRNA expression is associated with poor prognosis in patients with gastric cancer. TRIM3 may play a protective role in gastric cancer by relieving the effects of cancer progressive genes and could be considered for further investigations as a prognostic biomarker.

Access to the COVID-19 services during the pandemic - a scoping review.

Appropriate accessibility to coronavirus disease 2019 (COVID-19) services is essential in the efficient management of the pandemic. Different geospatial methods and approaches have been used to measure accessibility to COVID-19 health-related services. This scoping review aimed to summarize and synthesize the geospatial studies conducted to measure accessibility to COVID-19 healthcare services. Web of Science, Scopus, and PubMed were searched to find relevant studies. From 1113 retrieved unique citations, 26 articles were selected to be reviewed. Most of the studies were conducted in the USA and floating catchment area methods were mostly used to measure the spatial accessibility to COVID-19 services including vaccination centres, Intensive Care Unit beds, hospitals and test sites. More attention is needed to measure the accessibility of COVID-19 services to different types of users especially with combining different non-spatial factors which could lead to better allocation of resources especially in populations with limited resources.

The Predictive Role of Parathyroid Hormone for Nonalcoholic Fatty Liver Disease following Bariatric Surgery.

Background: Morbid obesity is frequently complicated by chronic liver diseases, including nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), and fibrosis. Parathyroid hormone (PTH) is found to be elevated in morbid obesity due to the defective hepatic metabolism of vitamin D. Bariatric surgery is performed to help patients with BMI>40 kg/m2 to effectively lose weight, particularly in patients with obesity who are afflicted with complications such as NAFLD/NASH. Objective: This study aimed to evaluate the PTH level as a predictor of hepatic function in individuals with morbid obesity who have undergone bariatric surgery. Methods: Ninety subjects with morbid obesity referred for Roux en-Y gastric bypass surgery were recruited. After IRB approval, demographic profiles, anthropometric factors, liver biopsy, and laboratory tests were obtained. The two-dimensional shear wave elastography (2D-SWE) technique was applied to assess hepatic stiffness. Results: A significant reduction occurred six months after bariatric surgery in the anthropometric indices (p < 0.001), hepatic elasticity (p=0.002), alanine aminotransferase (p < 0.001), serum alkaline phosphatase (p < 0.001), gamma-glutamyl transpeptidase (GGT) (p < 0.001), and nonalcoholic fatty liver disease fibrosis score (NFS) (p < 0.001). Serum PTH concentration was not predictive of postsurgical liver fibrosis and steatosis at six months but could predict weight loss success rate. No significant alteration in serum PTH levels was observed between presurgical vs. postsurgical time points. Conclusion: A significant reduction was observed in the anthropometric parameters, liver enzymes, and hepatic elasticity after bariatric surgery. No significant effect was found on PTH levels.