The aim of this study was to systematically review the global epidemiology of Inflammatory Bowel Disease (IBD). IBD is a global concern, and its incidence is rising worldwide. We searched PubMed, Scopus, and Web of Science from 1 January 2000 to 14 July 2022 using MeSH keywords. All population-based studies that reported the incidence or prevalence of IBD, Crohn's disease (CD), or ulcerative colitis (UC) were included. Random effect models were applied to combine the prevalence and incidence. Findings from 215 studies were analyzed. The global prevalence rates of IBD, CD, and UC were 229.7 per 100,000 (95% confidence interval: 212.4 to 247.0), 84.2 (78.5 to 89.9), and 120.4 (110.5 to 130.3), and the incidence was 9.7 per 100,000 person-years (9.2 to 10.2), 4.0 (3.8 to 4.2), and 5.0 (4.6 to 5.3), respectively. The highest IBD and CD incidence were seen in Oceania (21.3 [12.9 to 29.7] and 12.2 [8.5 to 15.9], respectively), while the highest incidence of UC was reported in North America (9.8 [6.7 to 12.8]). According to the pooled prevalence, Europe had the highest prevalence rates of IBD and UC (348.4 [315.2 to 381.5] and 198.6 [181.6 to 215.6], respectively), whereas Oceania was the continent with the highest CD prevalence (173.6 [151.8 to 195.4]). Our findings showed that the incidence and prevalence of IBD in both developed and developing nations are mounting. Special focus should be placed on understanding and managing pediatric CD cases, necessitating targeted research and early interventions.
This study aimed to evaluate the leukocyte glucose index (LGI) as a discriminator between patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and those with type 2 diabetes mellitus (T2DM), and to examine its association with the triglyceride-glucose index (TyGI) in both conditions. LGI is derived from fasting plasma glucose (FPG) and leukocyte count, both of which may fluctuate under pathological conditions. LGI has been proposed as a predictor of disease severity and mortality. This cross-sectional study was conducted from 1 January 2024 to 1 September 2024 at the College of Pharmacy, University of Sulaimani, Sulaimaniyah, Iraq. Patients with MASLD were randomly selected. The primary outcome was LGI, calculated from FPG and total leukocyte count.. The secondary outcome was TyGI. A total of 126 patients were included and divided into three groups. Group I included patients with risk factors related to MASLD (n = 25), Group II included patients with MASLD (n = 51), and Group III included patients with T2DM (n = 50). Baseline characteristics did not differ significantly between Groups I and II, whereas Group III differed significantly from both Groups I and II. The median LGI value was significantly higher in Group III (1.53) than in Group I (0.793) and Group II (0.744) (p < 0.001). Significant positive correlations were observed between LGI and TyGI in Group II (r = 0.489, p < 0.001) and Group III (r = 0.705, p < 0.001). An LGI cutoff value of 1.167 significantly discriminated T2DM from MASLD, with a sensitivity of 86.1% and a specificity of 77.6%. LGI may help distinguish MASLD from T2DM and is significantly associated with TyGI in both conditions.
Inflammatory Bowel Disease (IBD) is a chronic inflammation of the gastrointestinal tract, the precise origins of which remain not fully elucidated. This study investigates the complex relationship between gut metagenomics and host transcriptomics in IBD patients, focusing on Ulcerative Colitis (UC) and Crohn's Disease (CD). One proposed theory suggests that microRNAs produced by the host may significantly influence IBD development by impacting the gut microbiota. Conversely, the gut microbiome may regulate the expression of host microRNAs, leading to dysfunction in the intestinal epithelium. An enrichment analysis was conducted to pinpoint associated pathways. To unravel this intricate interplay, the study utilized data from the IBDMDB database, selecting samples from adult individuals. The dataset comprised 50 paired metagenomic and host transcriptomic samples, including 8 controls, 18 UCs, and 24 CDs. Computational analyses and network constructions were applied to identify relationships between bacterial species, microRNAs, and other transcripts. This research offers valuable insights into the dynamic relationship between the gut microbiome and human transcriptomics in IBD, providing a deeper understanding of potential disease mechanisms. Furthermore, it sheds light on the complex tripartite network connecting bacterial species, microRNAs, and transcripts, contributing to a comprehension of IBD pathogenesis and the identification of novel therapeutic targets.
With growing evidence linking food antigens to inflammation and symptoms, our objective was to review the evidence for the impact of dietary factors on functional dyspepsia (FD) pathogenesis. FD is a common gastrointestinal disorder characterised by postprandial fullness, early satiety, epigastric pain, and burning. A systematic search of MEDLINE, EMBASE, PsycINFO, Scopus, and Cochrane databases was conducted for studies published between January 2000 and December 2024. Eligible studies included adults (≥18 years) with FD diagnosed using the Rome criteria. Data were synthesised narratively, and the risk of bias was assessed using ROBIS, RoB 2.0, and ROBINS-I tools. Fourteen studies met inclusion criteria, evaluating seven key dietary categories: FODMAPs/wheat, prebiotics/probiotics, capsaicin, peppermint-caraway and cinnamon oils, herbal therapies, medications, and ginger-based interventions. High-FODMAP foods, gluten, and capsaicin were linked to symptom exacerbation, with some studies noting impaired epithelial barrier function, immune activation, or microbiota alterations. Interventions with anti-inflammatory or microbiota-modulating effects, including probiotics, peppermint-caraway oil, herbal formulations, and ginger-based supplements, were found to mitigate symptoms. Our findings show that specific dietary components can be implicated in inducing inflammation and symptoms in FD. Stress and anxiety might be another triggering factor for FD; hence, we see the utility of antidepressants in some cases. Since the symptoms are related to inflammation in most cases, we propose using 'inflammatory dyspepsia' to represent the true presentation for those patients with inflammation detected in their gastrointestinal mucosa. Large-scale randomised trials are needed to confirm findings and refine dietary guidelines.
To evaluate the efficacy and safety of sphingosine-1-phosphate (S1P) receptor modulators in treating ulcerative colitis (UC) and Crohn's disease (CD). Inflammatory Bowel Disease (IBD) is a chronic immune-mediated condition that remains challenging to manage. S1P receptor modulators offer a novel therapeutic approach by targeting immune cell trafficking, potentially improving disease outcomes. A systematic review and meta-analysis were conducted by searching PubMed, Scopus, and Cochrane Library major electronic databases for randomized controlled trials (RCTs) investigating S1P receptor modulators in IBD. Clinical outcomes assessed included clinical remission, clinical response, endoscopic improvement, histologic remission, and serious adverse events. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using a fixed-effects model. Seven RCTs with a total of 2,597 patients were included. S1P receptor modulators significantly improved clinical remission (OR = 1.49, 95% CI: 1.21-1.84, p < 0.001), histologic remission (OR = 1.74, 95% CI: 1.31-2.31, p < 0.001), endoscopic improvement (OR = 1.58, 95% CI: 1.23-2.04, p < 0.001), and clinical response (OR = 1.27, 95% CI: 1.05-1.54, p = 0.01). The risk of serious adverse events did not significantly differ between treatment and placebo groups (OR = 1.28, 95% CI: 0.92-1.80, p = 0.14), suggesting a favorable safety profile. This meta-analysis supports S1P receptor modulators, particularly ozanimod and etrasimod, as effective and safe treatments for UC. Further studies are needed to assess long-term safety and direct comparisons with existing biologic therapies.
This study examined the associations between psychosocial factors, Irritable bowel syndrome (IBS) diagnosis, and quality of life (QOL) in both control and IBS groups. Additionally, we explored the potential influence of psychosocial factors on the onset of IBS and developed a machine-learning model for IBS prediction. IBS is a prevalent gastrointestinal disorder, with various factors predicting its severity and associated symptoms. Through convenience sampling, a cross-sectional study recruited participants diagnosed with IBS (n=134) and healthy controls (n=150) from Arak Gastroenterology Clinics. Linear regression assessed the impact of psychosocial factors on IBS symptom severity and QOL. Logistic regression analyzed the association of these factors with IBS onset. Machine learning algorithms were used to predict IBS based on psychosocial features. Instruments include IBS-SSS, IBS-QOL, Toronto Alexithymia Scale (TAS-20), Visceral Sensitivity Index (VSI), and Pain Catastrophe Scale (PCS). A total of 284 participants (61.27% females) were recruited in the study, with a mean age of 36.48±10.75 years. Compared to controls, IBS patients exhibited significantly higher scores on measures of pain catastrophizing scale (PCS, 40.95 vs. 27.73), somatization (13.91 vs. 6.49), and alexithymia (60.23 vs. 54.71) as well as lower VSI (40.54 vs. 72.10). For those with IBS, only difficulty identifying feelings and somatization remained associated with worse symptoms, while VSI presented an inverse correlation. Psychological factors were inversely related to QOL. Elevated levels of alexithymia (OR 1.06; 95% CI 0.48, 1.63), somatization (OR 1.80; 95%CI 1.12, 2.48), and PCS (OR 1.70; 95% CI 1.30, 2.10) were associated with a higher chance of developing IBS, while higher VSI (OR -1.65; 95% CI -1.89, -1.42) was protective. Among machine learning models, logistic regression based on these factors (excluding alexithymia) and age achieved good performance (AUC: 0.86, 95% CI: 0.78-0.94; Accuracy: 0.83, 95% CI: 0.73-0.90) in predicting IBS onset. Psychological factors were linked to worse IBS symptoms and quality of life. A machine learning model for IBS prediction presented promising results.
In this study, global and regional trends between 1990 and 2021 were examined by sex, level of development, and geography, and projected to 2025. Diarrheal disease continues to be a leading cause of morbidity and mortality in children under the age of five (U5). We assessed GBD 2021 data for U5 children in 204 countries, 21 regions, and 7 super-regions with joinpoint regression to analyze time trends, a hybrid ARIMA-ETS-ANN model to project prevalence and mortality until 2025, and longitudinal multilevel modeling to determine the effect of development level. Spatial clustering in 1990 and 2021 was assessed with Local Moran's I. In 2021, the global prevalence and mortality rates of diarrheal disease among children under five were 885.07 and 51.72 per 100,000 population, respectively. Between 1990 and 2021, global U5 mortality decreased by 80.4%, and prevalence by 71.8%. The heaviest burden remained in Sub-Saharan Africa (SSA) and South Asia (SA), though all super-regions experienced statistically significant decreases. Joinpoint regression across the entire interval (1990-2021) revealed significant overall reductions in mortality (AAPC -5.15; 95% CI: -5.19, -5.10) and prevalence (AAPC -3.98; 95% CI: -4.03, -3.94). Hybrid forecasts predict ongoing decreases through 2025, with prevalence reaching 631.3 and mortality 36.6 per 100,000 population worldwide. Multilevel models revealed steeper annual reductions in low- and medium-Human Development Index (HDI) nations, corroborated by significant time-HDI interaction terms (β=79.76 for prevalence; β=7.50 for mortality; both p<0.001), although such countries had a persisting higher absolute burden. Spatial analysis revealed enduring hotspots in SSA and SA in both 1990 and 2021, and the formation of new clusters in several high-income countries. Coldspots occurred primarily in high-income and island nations. Significant global advancements have lessened the burden of diarrheal disease in U5 children; yet, ongoing disparities attributed to unsafe water, poor sanitation and hygiene, undernutrition, and low maternal education underscore the necessity for combined water, sanitation, and hygiene interventions, rotavirus immunization, and community-based health education in high-risk areas.
This study evaluated the prognostic value of Strasberg classification on 30-day bile duct patency and explored relevant clinical and procedural factors. Bile duct injury (BDI) is a serious complication of cholecystectomy that may influence early outcomes after endoscopic retrograde cholangiopancreatography (ERCP). We retrospectively reviewed 33 patients with BDI treated with ERCP at Dr. Moewardi Hospital from January 2023 to May 2025. Data included demographics, laboratory results, cholecystectomy type, timing of diagnosis and repair, and injury severity (minor: A-C; major: D-E). The primary outcome was bile duct patency at 30 days, assessed by imaging and clinical indicators. Statistical analyses included chi-square, Fisher's exact, Kaplan-Meier survival, and ROC curves. Patients had a mean age of 45.9 years; 54.5% were female, and 54.5% had laparoscopic cholecystectomy. Minor and major injuries were observed in 51.5% and 48.5%, respectively. 63.6% achieved bile duct patency by day 30. No significant associations were found between demographic, laboratory, procedural variables, and either injury severity or outcomes (all p>0.05). Kaplan-Meier analysis revealed significantly longer patency in minor injuries compared to major injuries (mean 25.88 vs. 20.88 days, p=0.030). This study highlights Strasberg classification as an independent predictor of early bile duct patency after ERCP. Other common clinical factors did not significantly influence outcomes. These findings underscore the importance of Strasberg classification not only for injury assessment but also for guiding early postoperative management and monitoring. Larger prospective studies are needed to confirm these results and to optimize prognostic tools for BDI care.
This systematic review and meta-analysis evaluated the impact of probiotics on postoperative complications and intestinal barrier integrity markers in patients with colorectal cancer (CRC) undergoing surgery. Postoperative complications pose a substantial challenge in CRC. Probiotics have been shown to alleviate these complications through various mechanisms, including improving intestinal barrier integrity. Following PRISMA guidelines, a systematic search was conducted in MEDLINE, Web of Science, Cochrane Library, and Scopus up to February 1, 2026, to identify randomized controlled trials (RCTs) investigating the effects of probiotics on post-surgical complications, recovery parameters, and functional intestinal barrier biomarkers (lactulose/mannitol [L/M] ratio and transepithelial electrical resistance [TER]). Statistical analysis was performed using random-effects models in R. Effect sizes were expressed as risk differences (RD) for binary outcomes and standardized mean differences (SMD) for continuous outcomes. Heterogeneity was assessed using Cochran's Q and I² statistics (PROSPERO: CRD420251172153). Eleven RCTs involving 1,234 CRC patients were included. Probiotic supplementation significantly reduced the risk of septicemia (RD=-0.158, p=0.029), surgical site infection (RD=-0.060, p=0.024), respiratory tract infection (RD=-0.079, p<0.001), central line infection (RD=-0.096, p=0.007), diarrhea (RD=-0.137, p=0.005), and abdominal distension (RD=-0.172, p=0.005). Functional intestinal barrier markers were significantly improved, evidenced by a decreased L/M ratio (SMD=-1.78, p=0.018) and increased TER (SMD=1.10, p<0.001). Furthermore, the duration of postoperative antibiotic use was significantly shortened (SMD=-0.45, p=0.001). No significant differences were observed for bacteremia, abscess, urinary infection, ileus, anastomotic leak, pyrexia, or hospital stay (p>0.05). Sensitivity analyses showed outcome variability, and substantial heterogeneity existed for pyrexia, septicemia, ileus, and the L/M ratio. Probiotics reduced the risk of specific infectious and gastrointestinal complications and enhanced intestinal barrier function after CRC surgery, highlighting their potential as a safe and effective adjunct to improve postoperative outcomes.
To compare the efficacy and safety of supraglottic airway (SGA) vs. infraglottic airway (IGA) in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). To optimize patient outcomes by improving airway control, various airway techniques have been employed for sedation during ERCP. However, there is uncertainty about the noninferiority of SGA devices compared to IGA. We performed a systematic review in PubMed, Embase, and Cochrane Library databases, searching for randomized and non-randomized studies comparing SGA vs. IGA in patients undergoing ERCP and reporting at least one of the outcomes of interest. The primary outcomes were procedure time, incidence of hypoxia, and blood staining events. Statistical analyses were performed using R language 4.3.1. Odds ratio (OR) was used for binary outcomes and mean difference (MD) for continuous outcomes with their respective 95% confidence interval (CI). Heterogeneity was assessed using the Cochran Q test and I² statistics. The study comprised 1 randomized controlled trial (RCT) and 3 observational studies involving 280 patients. Among them, 160 were allocated to the SGA group and 120 to the IGA group. When comparing procedure times, there was no statistically significant difference between SGA and IGA (MD -1.51 minutes; 95% CI -6.10 to 3.09 minutes; p = 0.52; I² = 62%). Regarding blood staining, statistical significance favored IGA over SGA (OR 2.67; 95% CI 1.12 to 6.41, p = 0.027; I² = 0%). No statistically significant difference in procedure time was observed between SGA and IGA. However, IGA exhibited a favorable outcome regarding reduced blood staining compared to SGA. Further studies comparing similar outcomes are necessary to assess such associations better.
This study aimed to analyze trends in the etiologies of liver transplants at Abu Ali Sina Hospital, Shiraz, Iran, from 2020 to 2024. Liver transplantation (LT) is a crucial treatment for end-stage liver disease (ESLD). Over time, the etiologies leading to LT have evolved due to changes in disease prevalence, advancements in medical treatments, and public health interventions. Etiologies of LT were categorized into nine groups: acute liver failure, autoimmune disorders, alcoholic steatohepatitis, liver cancer, vascular, metabolic dysfunction-associated steatohepatitis (MASH), viral hepatitis, metabolic disorders, and others. Trend analysis was performed using Python 3.12 programming language with appropriate libraries. A total of 1579 patients, 59.9% male with a mean age of 45.12 years (SD: 13.52), were analyzed. Autoimmune disorders emerged as the leading cause of LT, increasing from 32.2% in 2020 to 40.6% in 2024 (p-trend = 0.039). Viral hepatitis cases decreased significantly from 18.1% to 3.0% (p-trend = 0.033). Liver cancer became the third leading cause in 2021, replacing viral hepatitis, while MASH consistently remained the second leading cause. The significant shifts in LT etiologies underscore the success of public health interventions in reducing the burden of viral-related ESLD. Additionally, the findings highlight the need for ongoing research into the prevention, early diagnosis, and management of autoimmune liver diseases, MASH, and liver cancer. These findings provide critical insights for clinicians and policymakers to enhance liver disease management and allocate resources effectively.
This research aimed to identify the possible links between Non-alcoholic fatty liver disease (NAFLD) and gestational diabetes mellitus (GDM) by examining shared genes and pathways through the use of bioinformatics tools. NAFLD presents several potential risk factors for the onset of GDM. We downloaded relevant microarray datasets from the Gene Expression Omnibus (GEO) database for screening common differentially expressed genes (DEGs) between NAFLD and GDM by GEO2R. Then, we used gene ontology analysis to explore the biological processes and KEGG pathways of NAFLD and GDM occurrence. The hub genes of each disease were screened by analysis of the PPI network, and the common hub genes were identified. We designed a co-expression network and miRNA hub gene regulatory network for selected hub genes by using GeneMANIA and miRNet platforms, respectively. We identified 521 and 185 DEGs for NAFLD and GDM, respectively. 10 shared genes (FOS, CD22, AMZ1, ANGPT2, ATP1B2, STAB2, EGR1, MMP9, CXCL9, and LCN2) were screened among DEGs of two diseases, with analysis revealing enrichment in pathways such as IL-7 and TNF signaling pathways. Then, common hub genes (FOS, MMP9, and CXCL9) were identified via PPI network analysis, which were strongly correlated with both diseases. In addition, has-mir-34a-5p and has-mir-335-5p were detected as shared miRs that target hubs. We found 3 shared hub genes involved in NAFLD and GDM. Our research established a connection between the two diseases and could aid in formulating possible intervention strategies aimed at addressing both disorders by utilizing these risk factors.
This study aimed to synthesize evidence on the prevalence of Barrett's esophagus (BE), estimate its global burden, and examine variation across studies. Accurate BE prevalence estimates are essential for developing effective screening and surveillance strategies. A systematic search was conducted in PubMed, Scopus, Web of Science, and EMBASE from inception to January 2026. Full-text articles and reference lists were also screened manually. Studies reporting BE prevalence in general or clinical populations were included. Extracted data covered study design, population characteristics, diagnostic criteria, biopsy protocols, geographic region, and publication period. Study-level analyses assessed methodological variability and temporal trends. Linear regression and generalized additive models were used to project BE prevalence through 2050. Fifty-two studies, including approximately 8.4 million participants from 24 countries, were analyzed. The pooled mean prevalence of BE was 5.76%, with estimates ranging from 0.06% to 37.4%. Prevalence was higher in symptomatic endoscopy cohorts than in population-based cohorts (4.8% vs. 1.2%, p < 0.001). Studies requiring histologic confirmation of intestinal metaplasia reported lower estimates than those using broader definitions. Significant heterogeneity was observed by region and publication period. Seattle biopsy protocol reporting was documented in 38.5% of studies and improved after 2010. Forecast models projected BE prevalence of 12.8-13.2% by 2050 using linear modeling and 11.2-11.8% using GAM. Reported BE prevalence varies widely, mainly due to differences in diagnostic criteria, study populations, and methodology. Standardized definitions, biopsy protocols, and reporting practices are needed to improve epidemiologic accuracy and guide screening.
This study aimed to ascertain the equivalence in meaning and measurement qualities of two assessment tools, namely the Patient Assessment of Upper Gastrointestinal Symptom Severity Index (PAGI-SYM) and Quality of Life (PAGI-QOL), in a sample of individuals with upper gastrointestinal disorders in Iran. There is substantial demand for reliable and accurate research instruments in researchers' native language to evaluate specific concepts of interest. The Rome Foundation Guideline was employed as a framework for this investigation. To this end, a rigorous translation process was utilized, involving forward translation by two independent translators, reconciliation, and backward translation. An expert committee evaluated the semantic, idiomatic, experiential, and conceptual aspects of the translations. A panel of gastroenterologists assessed the content and face validity of the translated questionnaires. Cognitive debriefing sessions were conducted involving patients with dyspepsia or gastroesophageal reflux disease. Concurrent validity of the questionnaires was ascertained by comparing them with the 36-item Short Form Health Survey (SF-36). The findings presented satisfactory translation of the assessment tools, with initial assessments of internal consistency and construct validity demonstrating suitability. In this particular sample, the internal consistency of the PAGI-SYM was excellent (Cronbach's α range: 0.62-0.92), while the PAGI-QOL indicated good internal consistency (Cronbach's α range: 0.68-0.95). Further, there were strong correlations between the total scores of PAGI-SYM and PAGI-QOL, as well as all SF-36 general health subscale (-0.469 and 0.572, p-value<0.001), demonstrating concurrent validity. Both PAGI-QOL and PAGI-SYM instruments exhibited validity and reliability when applied to assess upper gastrointestinal disorders.
This study aimed to evaluate the preventive and therapeutic effects of cepharanthine on APAP (N-acetyl-para-aminophenol )-induced liver and kidney injury in an experimental model. Acetaminophen (APAP) is widely used as an analgesic and antipyretic drug; however, its overdose can cause acute liver and kidney injury. Cepharanthine, a natural alkaloid with antioxidant properties, has been proposed as a potential protective agent. In this experimental study 40 Male NMRI mice were divided into five groups: Control, Sham, APAP-treated, APAP + preventive cepharanthine, and APAP + therapeutic cepharanthine groups. Liver and kidney function markers, including ALT, AST, BUN, creatinine, total antioxidant capacity (TAC), and malondialdehyde (MDA), were measured. Histopathological analysis was performed to assess tissue damage. Statistical analysis was conducted using ANOVA with a significance threshold of p < 0.05. APAP administration significantly increased ALT, AST (p < 0.001), and MDA (p < 0.01) while reducing TAC levels (p < 0.01) in liver and kidney tissues. Cepharanthine, particularly in the therapeutic group, reduced ALT levels (p < 0.05) and improved liver histology but did not significantly alter AST or TAC in the prevention group. In contrast, cepharanthine failed to improve kidney function markers and worsened histological damage, leading to increased tubular casts and hemorrhagic areas. Cepharanthine exhibited partial hepatoprotective effects against APAP-induced liver injury but did not improve kidney damage. So, this natural alkaloid does not confer a significant protective effect against acute kidney injury.
This study aimed to assess the trend and geographical distribution of colorectal cancer (CRC) in Fars province from 2011 to 2024, and its changes during COVID-19. Research has indicated that the risk of CRC varies significantly across different regions of the world. From 2011 to 2024, data from 1,453 CRC patients who were registered in the Shiraz Colorectal Cancer Surgery (SCORCS) program were analyzed. Using R software (v4.2.0), we applied interrupted time series analysis to evaluate the impact of COVID-19 on CRC incidence and mortality. Spatial distribution was examined with ArcGIS (v10.4.1), and Moran's I test was used to determine high- and low-risk regions. A 5% significance level was applied to all analyses. In this study, 56.2% of the patients were men and 43.8% were women. Most patients (49%) were between 30 and 59 years old. Rectal cancer was slightly more common (57.7%) than colon cancer (41.8%), and only a very small number (less than 0.5%) had both. About half of the patients were classified as T3, and over 80% already had metastasis. At the pandemic onset, both outcomes showed a significant immediate increase, followed by a significant post-pandemic decline in slope. Among the studied areas, Kazerun and Jahrom had the highest incidence rate, while Zarqan and Kazerun showed the highest mortality rate. This study shows that CRC incidence and mortality declined during COVID-19, likely due to restrictive policies. However, the high rates in some cities of Fars province highlight the need for targeted interventions to reduce the disease burden.
We analyzed global and regional trends from 1990 to 2021, examined the impact of the Human Development Index (HDI), and compared spatial clusters in 1990 and 2021. Alcohol-related cirrhosis is a major cause of liver-related mortality, but long-term patterns remain incompletely understood. Age-standardized mortality rates (ASMRs) for alcohol-related cirrhosis were obtained from the Global Burden of Disease 2021 study for 1990-2021. Temporal trends were evaluated using joinpoint regression. Differences by country development status (more vs. less developed using an HDI 0.700 cutoff) were assessed with multilevel longitudinal modeling. Spatial clustering was identified with Local Moran's I. Globally, the ASMR of alcohol-related cirrhosis declined from 5.40 to 4.08 per 100,000 between 1990 and 2021, a 24% reduction, with larger relative declines observed in females than in males. The average annual percentage change (AAPC) in ASMR was -0.89%, with the steepest decline in North Africa and the Middle East and an increase in Central and Eastern Europe and Central Asia. Multilevel analysis over 1990-2021 showed faster yearly declines in ASMR in more developed countries compared with less developed ones. Spatial analysis revealed a shift of hotspots from Latin America and Africa in 1990 to Eastern Europe and Central Asia in 2021. Global alcohol-related cirrhosis mortality has declined but remains uneven, rising in Central and Eastern Europe and Central Asia and falling faster in more developed countries. Further progress needs targeted alcohol control and stronger health systems, especially in less-developed and hotspot regions where high-burden countries cluster.
To identify prognostic biomarkers in colorectal cancer (CRC) using an integrative systems biology approach combining transcriptomics, network topology, and immune profiling. Advanced CRC prognosis remains poor due to a lack of biomarkers capturing tumor-immune interactions. Current single-gene markers often overlook the network-based nature of tumorigenesis. We analyzed TCGA-COAD data (n = 463 tumor, n = 85 normal) using GEPIA3 with thresholds of |log_2FC| > 2 and adjusted p. value < 0.05. Protein-protein and gene-gene interaction networks were constructed via STRING (confidence > 0.4) and GeneMANIA. Hub genes were prioritized by intersecting degree and betweenness centrality using Cytoscape. Prognosis was assessed using cSurvival (Kaplan-Meier) and immune correlations via TISDB. Protein expression was verified in the Human Protein Atlas and external validation was performed to justify accuracy of candidate biomarkers. Analysis revealed 992 DEGs (498 up-regulated and 494 down-regulated) enriched in extracellular matrix organization and innate immune pathways. Eight dual hub genes were identified; PRELP and TAGLN significantly predicted overall survival. High PRELP (p= 0.014) and TAGLN (p = 0.039) expression predicted poor prognosis. Both positively correlated with innate immune cells (NKT/NK cells) but negatively with activated CD4+ T cells, suggesting immune exclusion. PRELP and TAGLN are novel dual prognostic biomarkers linking stromal remodeling to immunosuppression in CRC. High tissue expression serves as a marker of desmoplastic stroma and poor survival, emphasizing context-dependent biomarker evaluation.
The molecular mechanism of this relationship can be detected that promote the transition from colitis to colon cancer via system biology tools is the main aim of this study. There is a correlation between colitis and associated colon analysis. The differentially expressed microRNA and gene profiles of samples with colitis and colon cancer are extracted from the Gene Expression Omnibus (GEO) database and assessed using the GEO2R program and the CluePedia plugin of Cytoscape software to identify crucial actors and controlled genes or microRNAs. Analyses revealed microRNA analysis was not suitable tool to detect molecular mechanism of colitis to associated colon cancer in mouse model but the gene expression profile assessment leads to introduce CLASP1, CENPM, KIF18A, PRS7, CENPI, ZWINT, SPC24, and CENPK as the critical genes that promote this transition in fibroblast cells of colon cancer. Regulation of ribosome and kinetochore was suggested as a possible treatment to prevent colitis - colon cancer transition.
Inflammatory bowel disease (IBD) is a chronic condition characterized by immune dysregulation and intestinal inflammation, with anti-tumor necrosis factor α (anti-TNFα) therapies being a key treatment strategy. However, therapeutic responses vary across patients due to genetic factors, necessitating the identification of predictive biomarkers to optimize outcomes. This study employs bioinformatic approaches to investigate the deleterious effects of SNPs in IBD-associated genes, focusing on the structural implications of HFE gene variants and the impact of TNFRSF1B 3' UTR SNPs on miRNA binding site alterations. The study utilized a systematic literature review to identify genes influencing drug response in IBD, followed by SNP detection. SNPs were filtered based on population frequencies using global databases (gnomAD, ExAC) and Iranome for region-specific data. Structural and functional impacts of missense variants were evaluated using in silico tools and protein domain analysis via InterPro and UniProt. Additionally, molecular dynamics simulation indicated structural changes in HFE gene variants, RNA-seq data analyzed differential gene expression, and miRNASNP-v3 predicted miRNA binding site alterations in 3' UTR regions. A comprehensive bioinformatics approach identified 41 key IBD drug response genes contributing to cellular pathways, with 69 coding sequence SNPs and 27 3'-UTR SNPs selected for analysis. Coding SNPs, including ABCB1 and HFE variants, were predicted to significantly alter protein structure and stability. RNA-seq analysis revealed TNFRSF1B upregulation in IBD patients, and its 3'-UTR SNPs were shown to affect miRNA binding. Molecular dynamics simulation demonstrated structural instability in the HFE H63D variant, suggesting functional disruption. This study explores genetic variations influencing anti-TNF therapy responses in IBD patients. Polymorphisms like HFE rs1799945 and TNFRSF1B SNPs are identified as pivotal markers for personalized treatment strategies. Computational findings highlight their clinical potential, emphasizing the need for experimental validation to advance precision medicine and improve therapeutic outcomes and quality of life in IBD management.