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Background: In regions with a high prevalence of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, coinfected patients face a heightened risk of developing hepatocellular carcinoma (HCC), termed HBV/HCV-related HCC (HBCV-HCC). We aimed to investigate the contribution of preexisting chronic hepatitis B (CHB) and subsequent chronic hepatitis C (CHC) to the development of HBCV-HCC., Methods: We examined HBV's involvement in 93 HBCV-HCC cases by analyzing HBV DNA integration as an indicator of HCC originating from HBV-infected hepatocytes, compared with 164 HBV-HCCs and 56 HCV-HCCs as controls., Results: Next generation sequencing revealed that 55% of HBCV-HCCs exhibited clonal HBV integration, which falls between the rates observed in HBV-HCCs (88%) and HCV-HCCs (7%), with similar integration patterns to HBV-HCCs. Common HCC somatic mutation analysis indicated HCV superinfection in HBCV-HCCs correlated with increased mutation rates in the telomerase reverse transcriptase (TERT) promoter and beta-catenin genes. Transcriptome analysis showed a prevalence of replicating HCV over HBV in HBCV-HCCs, with preexisting HBV exerting a proliferative role. The comparison of clinical characteristics revealed similarities between HBCV-HCC and HCV-HCC patients, including later onset for HBCV-HCC, possibly due to HCV superinfection slowing carcinogenesis. Notably, HBCV-HCCs with the same driver mutation, HBV integration at the TERT promoter, tended to develop later and showed a better prognosis post-tumor resection than HBV-HCCs., Conclusions: Our findings shed light on the interplay between preexisting CHB and subsequent CHC in elevating the risk of HBCV-HCC. These insights are crucial for understanding viral etiology-specific carcinogenesis and guiding surveillance policies for HBCV-HCC post-antiviral therapy., Competing Interests: Declarations. Ethics approval and consent to participate: The clinical samples and data were collected according to the protocol approved by the National Taiwan University Hospital Research Ethics Committee (201701026RINA) with written informed consent. Consent for publication: Not applicable. Competing interests: PJC is the consultant and received a grant from TCM Biotech. STT and YCW are TCM Biotech employees. YT received research funding from AbbVie, Gilead Sciences, Sysmex, Janssen, GlaxoSmithKline and FUJIREBIO. YT received lecture fee from Gilead Sciences, GlaxoSmithKline and HU frontier. YYL, YCW, and STT are the inventors for the probe design used in the current study., (© 2025. The Author(s).)

Background: Autism spectrum disorder (ASD) is a persistent neurodevelopmental disorder affecting brains of children. Mounting evidences support the associations between gut microbial dysbiosis and ASD, whereas detailed mechanisms are still obscure., Methods: Here we probed the potential roles of gut microbiome in ASD using fecal metagenomics and metabolomics., Results: Children with ASD were found to be associated with augmented serum cytokines milieu, especially TNFα. Metagenomic analysis generated 29 differential species and 18 dysregulated functional pathways such as Bifidobacterium bifidum, Segatella copri, and upregulated 'Sphingolipid metabolism' in children with ASD. Metabolomics revealed steroid hormone dysgenesis in children with ASD with lower abundances of metabolites such as estriol, estradiol and deoxycorticosterone. A three-way association analysis showed positive correlations between TNFα and microbial function potentials such as 'Bacterial toxins' and 'Lysosome', indicating the contribution of microbial dysbiosis to neuroinflammation. TNFα also correlated positively with 'Sphingolipid metabolism', which further showed negative correlations with metabolites estriol and deoxycorticosterone. Such results, in consistent with current findings, revealed the contribution of increased TNFα to upregulated sphingolipid metabolism, which further impaired steroid hormone biosynthesis., Conclusion: Our study proposed the gut microbial 'TNFα-sphingolipids-steroid hormones' axis in children with ASD, which may provide new perspectives for developing gut microbiome-based treatments in the future., Competing Interests: Declarations. Ethics approval and consent to participate: All research was approved by the Ethics Committee of the Lishui Second People’s Hospital, Zhejiang, Chia. Informed written consent was obtained from each of the participants before enrollment. Consent for publication: All the authors approve the publication of this article and this version of the manuscript. Competing interests: The authors declare no conflicts of interest., (© 2024. The Author(s).)

Background/aims: The increasing use of biologic therapies for moderate to severe inflammatory bowel disease (IBD) highlights the importance of optimal treatment sequencing, particularly after vedolizumab (VDZ) exposure. Studies comparing the effectiveness of ustekinumab (UST) and antitumor necrosis factor (anti-TNF) agents post-VDZ are limited., Methods: This retrospective study analyzed VDZ-experienced IBD patients treated with UST or anti-TNF (adalimumab and infliximab) from May 2019 to January 2024. We conducted a comparative analysis of the 52-week treatment persistence between UST and anti-TNF therapies, while also identifying independent predictors that influence 52-week persistence., Results: The study included 110 participants, with 40 diagnosed with ulcerative colitis (UC) and 70 with Crohn's disease (CD). Demographics were comparable across treatment groups. The primary discontinuation reason for VDZ was secondary non-response. Kaplan-Meier analysis revealed that UST demonstrated superior 52-week persistence in overall IBD, CD and UC patients, compared to anti-TNF. Cox regression analysis also showed UST's superiority in overall IBD (HR: 0.15, 95% CI: 0.05-0.45, p < 0.001), CD (HR: 0.09, 95% CI: 0.01-0.68, p = 0.02), and UC (HR: 0.28, 95% CI: 0.08-0.996, p = 0.049). The independent predictors for 52-week treatment persistence are Crohn's disease (Odds Ratio: 7.151, 95% CI: 1.763-28.995, p = 0.006) and UST treatment (Odds Ratio: 7.912, 95% CI: 1.789-34.992, p = 0.006). Notably, UST required more frequent dosing adjustments than anti-TNF, although both treatments exhibited comparable safety profiles., Conclusions: UST demonstrated superior 52-week treatment persistence in IBD patients previously treated with VDZ compared to anti-TNF agents, albeit with a need for more frequent dose adjustments., Competing Interests: Declarations. Ethical approval and consent to participate: The study was approved by the Institutional Review Board (IRB) of the Chang Gung Medical Foundation (approval document No. 202400030B0: “Diagnosis, Treatment, and Prognosis of Inflammatory Bowel Disease”). The IRB waived the requirement for signed informed consent from individual patients for reviewing medical records in the electronic medical record system as it was a retrospective study. Consent for publication: Not applicable. Financial disclosures: This study was not funded by grants or other financial sponsors. The authors have no financial arrangements for the company whose products are discussed in this manuscript. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome, a rare autosomal recessive disorder, exhibits genetic heterogeneity with the VIPAS39 gene pathological variants being a distinct contributor., Results: We present two related patients from Kosovo, describing the clinical, genetic, and therapeutic aspects of the syndrome. The identified novel VIPAS39 pathological variants (c.762G > A; c.1064&#95;1082delinsAGTG) emphasize the complex phenotypic expression of ARC syndrome. A systematic literature review identified 8 VIPAS39-related ARC cases with notable variability in clinical features. Prognostically, patients fell into severe and milder groups, with some reaching adolescence. Our report aligns with others noting milder ARC courses and emphasizes the value of genetic testing, especially in atypical presentations. Challenges included incomplete literature data, early mortality affecting diagnostic workup, and limited VIPAS39-related ARC cases. Comparisons with the more prevalent VPS33B pathological variants revealed no distinct clinical differences., Conclusion: Our study expands understanding of ARC syndrome, highlighting its genetic diversity and clinical variability. Milder presentations underscore diagnostic challenges and the potential prevalence of undiagnosed cases. Increased awareness and comprehensive genetic testing are crucial for early and accurate diagnosis., Competing Interests: Declarations. Ethics approval and consent to participate: Ethical approval was not required for this study as it is a case report, which does not fall under the scope of research requiring ethics committee approval. Consent for publication: Consent for publication was obtained from the parents of the individuals featured in the manuscript using our institutional consent form. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Background: The access to anti-cancer medications is influenced by policies formed via the convergence of various stakeholders. The aim of this study is to identify and analyse the stakeholders involved in formulating and implementing policies related to the accessibility of anti-cancer medications in Iran and their interactions that are relevant to the outcomes of these policies for the first time., Methods: To achieve the objectives, a novel multistage social network analysis (SNA)-based approach that includes three phases is proposed. First, the actors were identified by a team consisting of multidisciplinary knowledgeable experts through 15 comprehensive interviews. Then, the influence relationships of these actors were comprehensively analysed through in-depth interviews with nine key informants involved in pharmaceutical policies through a structured questionnaire. Finally, a novel network of actors was determined accordingly, and a SNA-based approach proposed to reveal the intrinsic roles and various aspects of the importance of the network's actors., Results: The study identified a total of 45 actors, which were then classified into 4 categories on the basis of their public or private nature and their foreign or domestic origin. This established network helped in creating a comprehensive view of the main actors, and can help policymakers to solve the problems related to access to anti-cancer medications more effectively and prevent the creation of these problems in the future. In this way, the network identified specific actors that can benefit from increased attention and dialogue. The computational results revealed that the Iran Food and Drug Administration (IFDA), Pharmaceutical Importer Companies (PharIc) and Pharmaceutical Manufacturing Companies (PharMC) were highly important actors in terms of their connectivity to other actors. Additionally, law enforcement agencies (LEA) have shown limited effectiveness within this network., Conclusions: This study highlights the importance of complex relationships among various actors and proposes a novel SNA-based approach to analyse them. Regarding the main steps of the proposed approach and the findings, it is imperative for pharmaceutical policy plans to involve a diverse group of experts from the beginning, prioritizing the preferences of stakeholders, and providing a patient-centred approach to prevent the worsening of resource shortages., Competing Interests: Declarations. Ethics approval and consent to participate: Written informed consent was obtained from all the participants. The protocol for this study was approved by the National Institute of Medical Sciences Research Development of Iran (NIMAD ID: 996384). A comprehensive description about the study was introduced to the participants; they were allowed to reject answering or withdrawing at any time thereafter. The participants were assured that their answers would be kept confidential and that their names would not be disclosed during the study and in the final report. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Today, malnutrition is one of the biggest health crises for children in the world. Access to accurate and high-quality data is very important to establish policies to deal with it. Registries are considered valuable tools for data collection and management of child malnutrition. Designing a dataset is the first step toward developing a registry system., Objective: This study aimed to determine the minimum data elements for the Child Malnutrition Registry System (CMRS)., Methods: In this descriptive and cross-sectional study, firstly, data elements were extracted from reviewing scientific papers, reviewing existing systems, and conducting interviews with experts. Then, the extracted data elements were validated using an expert panel and Delphi technique. The criterion for accepting the final data elements in the registry system was based on a collective agreement, and it was when 75% of the experts collectively agreed upon a particular data element., Results: A dataset was designed using the determined minimum data elements, including administrative data elements with three sub-categories (demographic, socioeconomic, and healthcare providers) and clinical data elements with 11 sub-categories (medical history, anthropometric indicators, clinical examination, nutritional data, physical activity and sleep, lab tests, para-clinical tests, diagnosis, complications, care procedures, life status, and follow-up). The number of final data elements in administrative and clinical categories were 47 and 251, respectively., Conclusion: A comprehensive and accurate dataset provides conceptual structures that are the basis for developing the children's malnutrition registry system. The result of this study can fill the existing gaps in collecting, storing, and analyzing child malnutrition data. Furthermore, it can play an effective role in creating a successful strategic plan for improving child malnutrition., Competing Interests: Declarations. Ethics approval and consent to participate: Ethical approval for the study was obtained from the Ethical Committee of Iran University of Medical Sciences (IR.IUMS.REC.1397.1083). All methods were carried out in accordance with relevant guidelines and regulations. Informed consent was obtained from all participants. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: The colorectal cancer mortality rate in China has exceeded that in many developing countries and is expected to further increase owing to multiple factors, including the aging population. However, the optimal policy for colorectal cancer screening is unknown., Methods: We synthesized the most up-to-date data using a 12-state Markov model populated with a cohort of Chinese men and women born during 1949-1988, and evaluated 16 conventional and 40 risk-tailored schemes for colorectal cancer screening, considering possible combinations of age (starting at 40 + years and ending at 75 years), frequency, and strategy (standard colonoscopy, fecal immunochemical testing with colonoscopy if positive, or risk-tailored). We projected the incidence and mortality of CRC, cost, and quality-adjusted life years for 2023-2038; and performed incremental cost-effectiveness, probability acceptability, and sensitivity analyses to identify the optimal scheme and the factors affecting this choice., Results: By 2038, all standard colonoscopy, colonoscopy following fecal immunochemical testing, and risk-tailored schemes were effective in reshaping China's colorectal cancer trajectory, with relative reductions in colorectal cancer incidence and mortality rates of up to 34% and 33.7%, respectively, versus no screening. Two standard colonoscopy, one colonoscopy following fecal immunochemical testing, and four risk-tailored schemes were efficient using a starting age of 40 years. Among these options, a risk-tailored scheme (standard colonoscopy every 5 years for high-risk and annual fecal immunochemical testing screening for moderate-to-low-risk) had a high probability (31.1%) of being optimal (with ≥ 40% uptake for a high-risk population, in particular), given China's present per capita gross domestic product, and would yield the highest gain in quality-adjusted life years in 17 of 31 provinces., Conclusions: Our findings suggest the commencement of colorectal cancer screening at 40 years of age in China, and that risk-tailored and some conventional schemes would be effective and cost-efficient. These findings should be valuable for policy-making regarding cancer control and resource allocation., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Retrieval practice is a highly effective learning strategy that enhances long-term retention by encouraging the active recall of information. However, the optimal question format for maximizing knowledge retention remains uncertain. In this study, we compared the effect of very short answer (VSAQ) versus multiple-choice question (MCQ) practice tests on students' knowledge retention. By analyzing these two formats, we aim to identify the most effective approach to retrieval practice, thereby helping to optimize its implementation and improve learning outcomes., Methods: In this randomized within-subjects study, students (n = 45) practiced with both VSAQs and MCQs in an extracurricular lifestyle course, without receiving feedback. The final retention test consisted of identical questions in both formats. A 2 × 2 repeated measures ANOVA was used to determine the effect of question format in practice testing and final test on final test score. Additionally, digital questionnaires were used to explore students' test-taking experiences., Results: The VSAQs were answered incorrectly more frequently on the practice tests and final test. There was no main effect of practice question format on final test performance, and no interaction effect between question format on the practice and final test. Regardless of question format, most students thought the practice tests were beneficial for learning., Conclusions: We found no evidence indicating that either MCQ or VSAQ is more effective for knowledge retention during retrieval practice. The lower initial retrieval success in the VSAQs, indicated by the higher degree of incorrect answers on the practice tests, might have limited their effectiveness during retrieval practice. To optimize the use of VSAQs in retrieval practice, it seems important to improve initial retrieval success to maximize learning outcomes., Clinical Trial Number: Not applicable., Competing Interests: Declarations. Ethical approval and consent to participate: This study was approved by the LUMC Educational Research Review Board (OEC/ERRB/20231010/1). Participation in this study was voluntary and all students received verbal and written information prior to the study. Consent for publication: Upon initiation of the first practice test, students provided informed consent. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Gastrointestinal subepithelial lesions (SELs) range from benign to malignant. Endoscopic ultrasound (EUS)-guided fine-needle biopsy (EUS-FNB) is used widely for pathological diagnosis of SELs. Early diagnosis and treatment are important because all Gastrointestinal stromal tumors (GISTs) have some degree of malignant potential. Diagnosing SELs with EUS-FNB is more difficult than diagnosing other tumors because an accurate diagnosis of GIST requires a sufficient tissue sample for immunostaining, which is part of the diagnostic protocol. Moreover, EUS-FNB is less accurate for diagnosis based on samples from SELs measuring ≤ 2 cm. However, our retrospective study showed that more than 50% of patients with SELs ≤ 2 cm were diagnosed as GIST. Therefore, EUS-FNB needles are required with adequate sampling in SELs measuring ≤ 2 cm. Previously, we conducted a retrospective single-center study of SELs measuring ≤ 2 cm, and reported that EUS-FNB with a Fork-tip needle was superior to that with a Franseen needle in that the former acquires sufficient sample. This multicenter comparative open-label superiority study is designed to verify whether a 22G Fork-tip needle is superior to a 22G Franseen needle with respect to sample acquisition., Methods/design: Present study will randomly assign for 110 patients (55 in the Fork-tip needle group and 55 in the Franseen needle group) with SELs measuring ≤ 2 cm, all of whom are managed at one of the 10 participating endoscopic centers. The primary endpoint evaluates the superiority of a 22G Fork-tip needle over a 22G Franseen needle for collection of an adequate tissue specimen at the first puncture. The secondary endpoints compare successful puncture rate, procedure completion rate, number of adverse events, diagnostic suitability of the first puncture specimen for GIST, and the number of punctures required until adequate specimen collection., Discussion: The outcomes may provide insight into the optimal needle choice for diagnosis of SELs ≤ 2 cm, thereby aiding development of practice guidelines. Present study is expected to promote early definitive diagnosis of GISTs, thereby increasing the number of cases that can receive curative treatment and improving prognosis., Trial Registration: Japan Registry of Clinical Trials (JRCT; trial registration: jRCTs052230144). Registered December 13, 2023. (URL; https://jrct.niph.go.jp/re/reports/detail/76858 )., Competing Interests: Declarations. Ethics approval and consent to participate: This protocol has been approved by Wakayama medical University Certified Review Board (approval number. W-59). The results will be submitted to peer-reviewed journals and will be presented at international conferences. Informed consent will be obtained from all patients by investigator. Consent for publication: Not applicable. Competing interests: The authors declare that they have no competing interests., (© 2024. The Author(s).)

Background: Recent studies have highlighted the distinct ratio of PD-1 + Treg/PD-1 + CD8 for prognosis prediction. However, it remains unclear about the association of this ratio and tertiary lymphoid structures (TLS) with prognosis and response to neoadjuvant or conversion therapy in advanced gastric cancer., Methods: Firstly, fresh postoperative samples from 68 gastric cancer patients in Renji Hospital were collected. Meanwhile, immune cell infiltration as well as clinical prognosis analysis were conducted. Subsequently, we further systematically evaluated flow cytometry analysis of tumor samples and TLS expression in 38 gastric cancer patients with different response situations after neoadjuvant therapy. Also, a Renji conversion therapy cohort including 10 patients with complete matching samples before and after treatment was established to receive RNA sequencing analysis and multiplex immunohistochemistry (mIHC) tests. The corresponding TLS score and immune cell infiltration were further compared based on therapeutic response variations., Results: In general, the ratio of PD-1 + Treg/PD-1 + CD8>1 could be regarded as an independent predictor of prognosis in advanced gastric cancer patients. Moreover, PD-1 + Treg/PD-1 + CD8 < 1 and high expression of TLS could indicate better neoadjuvant therapy response and extended survival time in advanved gastric cancer patients. Besides, PD-1 + Treg/PD-1 + CD8 low &TLS high group could predict better progression free survival time (PFS) in complete response (CR) subgroup. In response group after conversion therapy, the number of PD-1 + CD8 + T cells significantly increased, mainly occurring outside the TLSs. Meanwhile, the TLSs were also considerably activated as we could observed., Conclusions: This study underlined that combining PD-1 + Treg/PD-1 + CD8 ratio and TLS were significantly associated with prognosis and preoperative treatment response in advanced gastric cancer. Inspiringly, these indicators have the potential to elucidate the immune balance of advanced gastric cancer patients and can accurately guide subsequent therapeutic strategies., Competing Interests: Declarations. Ethical approval: All experiments have been approved by the Ethical Committee of the Shanghai Jiao. Tong University School of Medicine, Renji Hospital consent from the patient was obtained. Consent for publication: Not applicable. Competing interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024. The Author(s).)

Background: Helicobacter pylori infection causes gastritis, peptic ulcers, and gastric cancer. The infection is typically acquired in childhood and persists throughout life. The major impediment to successful therapy is antibiotic resistance. This systematic review and meta-analysis aimed to comprehensively assess the global prevalence of antibiotic resistance in pediatric H. pylori infection., Methods: We performed a systematic search of publication databases that assessed H. pylori resistance rates to clarithromycin, metronidazole, levofloxacin, amoxicillin, and tetracycline in children. The WHO region classification was used to group pooled primary and secondary resistance estimates along with 95% confidence interval (CI). H. pylori antibiotic resistance rates were retrieved and combined with odds ratios (95% CI) to investigate the global prevalence and temporal trends. Subgroup analysis of the prevalence of antibiotic resistance was conducted by country, age groups, and susceptibility testing methods., Results: Among 1417 records obtained initially, 152 studies were selected for eligibility assessment after applying exclusion criteria in multiple steps. Ultimately, 63 studies involving 15,953 individuals were included comprising data from 28 countries in 5 WHO regions. The primary resistance rates were metronidazole 35.3% (5482/15,529, 95% CI: 28.7-42.6), clarithromycin 32.6% (5071/15,555, 95% CI: 27.7-37.9), tetracycline 2.1% (148/7033, 95% CI: 1.3-3.6), levofloxacin 13.2% (1091/8271, 95% CI: 9.3-18.4), and amoxicillin 4.8% (495/10305, 95% CI: 2.5-8.8). Raising antibiotic resistance was detected in most WHO regions., Conclusions: The escalating trend of H. pylori antibiotic resistance in children warrants urgent attention globally. National and regional surveillance networks are required for antibiotic stewardship in children infected with H. pylori., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable; this manuscript does not include any details, images, or videos relating to an individual person. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Oxidative stress plays a crucial role in the pathogenesis of HBV. This study aimed to investigate the value of fibroblast growth factor 21 (FGF21) promoter methylation in the occurrence and development of chronic hepatitis B (CHB) oxidative stress., Methods: A total of 241 participants including 221 patients with CHB and 20 healthy controls (HCs) were recruited. Methylation level of FGF21 promoter in peripheral blood mononuclear cells was quantitatively determined. Enzyme-linked immunosorbent assay was used to assess oxidative stress in CHB patients., Results: Our study shows that the FGF21 methylation level was significantly lower in HBeAg-positive CHB patients compared to HBeAg-negative CHB patients and HCs (P < 0.0001). The oxidative stress of HBeAg-positive CHB patients was more severe. Further correlation analysis showed that there was a significant correlation between the methylation level of FGF21 promoter and the occurrence of oxidative stress in CHB patients. In addition, assessment based on FGF21 promoter methylation level proved effective for predicting oxidative stress occurrence and disease progression among CHB patients., Conclusion: FGF21 promoter methylation level is an important marker for predicting oxidative stress and disease progression in patients with CHB., Competing Interests: Declarations. Ethics approval and consent to participate: This study was conducted in accordance with the Declaration of Helsinki and was approved by the Medical Ethical Committee of Qilu Hospital of Shandong University. (#KYLL-202306-021-1). Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

In preclinical studies, GST-HG141, a novel hepatitis B virus (HBV) capsid assembly modulator displayed potent anti-HBV activity in vitro and strong efficacy in HBV animal models. A randomized, double-blind, ascending phase 1b trial assessed the pharmacokinetics, safety, and efficacy of GST-HG141 in chronic hepatitis B (CHB) individuals. Thirty treatment-naïve CHB patients were enrolled in three cohorts (25, 50, and 100 mg twice orally after meals daily) over 28 days, with 10 subjects per cohort (8:2 ratio for GST-HG141 and placebo). Dose-related safety and tolerability, pharmacokinetic profiles, and drug responses were evaluated. GST-HG141 exhibited a generally favorable safety profile across all doses with predominantly mild adverse reactions, including three cases of grade 1 transaminase elevations. Significant reductions in HBV DNA and pregenomic RNA (pgRNA) levels were observed across all doses of (25, 50, and 100 mg of GST-HG141, twice-daily) after 28 days of treatment. Pharmacokinetic analysis showed a consistent linear trend in GST-HG141 concentrations, with mean trough concentrations ranging from 75 to 240 ng/mL. These concentrations adequately covered the protein binding-adjusted EC50 (16.89 ng/mL) by factors of 4.4, 11.1, and 14.6 for doses of 25, 50, and 100 mg, respectively. Our study demonstrated GST-HG141's well-tolerated profile up to 100 mg over 4 weeks, alongside robust antiviral activity in CHB patients, supporting its progression into further clinical investigation for CHB management., Competing Interests: Declarations. Ethics approval and consent to participate: The clinical study protocol was approved by the Ethics Committee of the Jilin University First Affiliated Hospital-Clinical Research Institute (Approval Number 21Y088-001). Prior to participation, all patients provided written informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Gastric cancer (GC) remains one of the most lethal malignancies globally, with limited therapeutic options. Cancer-associated fibroblasts (CAFs), a diverse population of stromal cells within the tumor microenvironment (TME), play a central role in tumor progression and therapeutic resistance. However, the specific markers identifying tumor-promoting CAF subsets in GC have yet to be fully characterized., Methods: Through animal studies and RNA sequencing, complement C3 (C3) emerged as a key marker linked to tumor-promoting CAF subsets. Single-cell sequencing and multiplex immunofluorescence staining confirmed that C3 expression is predominantly localized within CAFs. Independent cohort analyses demonstrated a strong association between elevated levels of C3 + CAFs and poor clinical outcomes in GC patients. To further investigate, small interfering RNA (siRNA)-mediated knockdown of C3 in CAFs was employed in vitro, with subsequent experiments, including cell migration assays, cell viability assays, and immunofluorescence, revealing significant functional impacts., Results: C3 secreted by CAFs promoted Epithelial-mesenchymal transition (EMT) and accelerated cancer cell migration. Patients with minimal C3 + CAF infiltration exhibited a higher probability of deriving therapeutic benefit from adjuvant treatments. Furthermore, C3 + CAFs were associated with immunosuppressive effects and an immune-evasive microenvironment marked by CD8 + T cell dysfunction. A lower prevalence of C3 + CAFs correlated with improved responsiveness to immunotherapy in GC patients. Enrichment analysis highlighted pronounced activation of the NF-κB signaling pathway in C3 + CAFs relative to their C3 - counterparts, supported by elevated phosphorylation levels of IKK, IκBα, and p65 in C3 + CAFs compared to both C3 - CAFs and normal fibroblasts (NFs). Silencing p65 nuclear translocation in CAFs through siRNA significantly suppressed C3 secretion., Conclusions: The study suggests that NF-κB pathway-mediated CAF activation enhances C3 secretion, driving EMT, migration, chemoresistance, and immune evasion in GC progression. Targeting the NF-κB/C3 signaling axis in CAFs may offer a viable therapeutic strategy for GC management., Competing Interests: Declarations. Ethics approval and consent to participate: Informed consent was obtained from all patients before tumor sample collection, with all procedures receiving approval from the Clinical Research Ethics Committee at Fudan University Shanghai Cancer Center. Consent for publication: All authors consented to the publication of the study in this journal. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: This study aimed to explore the relationship between ultra-processed foods (UPFs) consumption and gut microbiota in patients with type 2 diabetes (T2D)., Methods: This cross-sectional study included 362 participants with T2D. UPFs consumption was assessed using a brief-type self-administered diet history questionnaire, quantified as the density of UPFs intake (g/1000 kcal). Gut microbial composition was evaluated via 16S rRNA gene sequencing. We investigated the association between gut microbiota, previously identified as relevant to T2D, and the density of UPFs intake using Spearman rank correlation coefficients. Multiple regression analysis, adjusting for age, sex, BMI, smoking status, exercise, and medication use, was conducted to further investigate these associations., Results: The mean age of participants was 68 (63-74) years. The density of UPFs intake showed significant associations with Bifidobacterium (r = 0.11, p = 0.031), Lactobacillus (r = 0.11, p = 0.046), Ruminococcus (r = -0.12, p = 0.019), Roseburia (r = 0.11, p = 0.045). After adjusting for covariates in multiple regression analysis, Ruminococcus and Roseburia showed modest negative (β = -0.11, p = 0.038) and positive (β = 0.12, p = 0.033) correlations, with the density of UPFs intake among participants with T2D, respectively., Conclusions: The density of UPFs intake was modestly inversely associated with Ruminococcus among patients with T2D and modestly positively associated with Roseburia., Competing Interests: Declarations. Ethics approval and consent to participate: The present study received approval by the ethics committee of the Kyoto Prefectural University of Medicine (no. ERB-C-534 and no. RBMR-E-466-5), and adhered to the principles of the Declaration of Helsinki. Written informed consent was obtained from all participants prior enrollment. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Acetaminophen (APAP)-induced acute liver injury (AILI) is the most prevalent cause of acute liver failure and mitochondrial dysfunction plays a dominant role in the pathogenesis of AILI. Mitochondrial transcription factor A (TFAM) is an important marker for maintaining mitochondrial functional homeostasis, but its functions in AILI are unclear. This study aimed to investigate the function of TFAM and its regulatory molecular mechanism in the progression of AILI., Methods: The roles of TFAM and DEAD (Asp-Glu-Ala-Asp) box polypeptide 3 X-linked (DDX3X) in AILI were determined with TFAM overexpression and DDX3X knockdown, respectively., Results: TFAM expression was suppressed in AILI patients. TFAM overexpression alleviated liver necrosis and mitochondrial dysfunction. Treatment of the AILI mice model with N-acetylcysteine (NAC), a drug used to treat APAP overdose, resulted in significant TFAM activation. In vivo experiments confirmed that TFAM expression was negatively regulated by DDX3X. Mechanistic studies showed that nuclear respiratory factor 2 (NRF-2), a key regulator of TFAM, was selectively activated after DDX3X knockdown via activated peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1α), in vivo and in vitro., Conclusions: This study demonstrates that depressed hepatic TFAM plays a key role in the pathogenesis of AILI, which is regulated by the DDX3X-PGC1α-NRF2 signaling pathway., Competing Interests: Declarations. Ethics approval and consent to participate: The content covered in this study was approved by the Ethics Committee in accordance with the requirements of local laws and regulations. All patients provided written informed consent before inclusion in the study. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Hepatitis B virus related compensated cirrhosis generally has a favorable prognosis until decompensation occurs. Bacterial infections are prevalent in Hepatitis B virus related decompensated cirrhosis.Bacterial infection and decompensated hepatitis B cirrhosis are mutually reinforcing. And it also interacts with and promotes certain decompensation-related events. However, the impact of bacterial infections on the progression from compensated to decompensated cirrhosis in Hepatitis B patients remains unclear., Methods: We retrospectively analyzed the baseline characteristics of 1,011 patients with Hepatitis B virus related compensated cirrhosis. Using time-dependent regression analysis, we evaluated whether bacterial infections increase the risk of decompensation, defined as the occurrence of ascites, hepatic encephalopathy, or variceal bleeding., Results: A total of 1,011 patients were retrospectively analyzed over a median follow-up period of 79 months. Bacterial infections were observed in 89 patients (8.8%). Respiratory and urinary tract infections were the most common bacterial infections.Decompensation occurred in 44.9% of patients with bacterial infections, compared to 9% of those without BIs. Patients with bacterial infections had a higher risk of decompensation ([OR] 1.024; 95% CI 1.016-1.032; p < 0.001) than those without bacterial infections., Conclusion: Our findings suggest that bacterial infections have a significant impact on the progression of hepatitis B virus related compensated cirrhosis, notably increasing the risk of decompensation., Competing Interests: Declarations. Ethics approval and consent to participate: The protocol of this study complied with the principles of the Declaration of Helsinki and was approved by the Human Ethics Committee of Tianjin Second People’s Hospital(Jin Er Ren Min Lun Shen Zi [2024] No. 69). According to the request of the Human Ethics Committee of Tianjin Second People’s Hospital, this retrospective study does not involve the collection and publication of patient names and addresses and other privacy, so informed consent can be exempted. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: Cancer is a significant public health issue in Iran, and its incidence has been on the rise in recent years. The objective of this study is to predict the incidence of total cancer in Iran using a Bayesian age-period-cohort (APC) model., Methods: Utilizing age-period-cohort modeling, this study assessed the multifaceted effects of age, period, and cohort on cancer incidence during the period spanning 2005 to 2017. Key metrics, including the net drift (representing the overall annual percentage change), local drift (indicating annual percentage changes within specific age groups), and longitudinal age curves (depicting expected age-specific rates over time), were computed. Moreover, the evaluation encompassed an analysis of period and cohort relative risks. To project the future age-standardized incidence rates of cancers from 2018 to 2027, Bayesian age-period-cohort analysis integrated nested Laplace approximations., Result: The age-standardized incidence rate and the absolute number of cancer cases in Iran showed an upward trend. The net drift was 1.79% (95% confidence interval, CI: 0.87% to 2.72%) for males and 3.31% (95% CI: 2.49% to 4.14%) for females. Local drifts remained consistently above zero for all age groups from 2005 to 2017, except for the under-5 age group in both males and females, and the 45-49 and 50-54 age groups in females. After accounting for period deviations, the risk of cancer incidence exhibited an exponential increase with age for both sexes. Based on the Bayesian age-period-cohort analysis, it is estimated that there will be around 210,701 new cancer cases in 2027. Moreover, the Age-Standardized Rate (ASR) for cancer is anticipated to reach 240.32 per 100,000 by 2027. The forecasts indicate a rise in cancer incidence rates across all age groups for both males and females., Conclusion: This study underscores the urgency of implementing targeted preventive strategies aligned with demographic shifts and lifestyle factors. Emphasizing the role of robust cancer registries, it advocates for continuous monitoring to inform evidence-based interventions., Competing Interests: Declarations. Ethics approval and consent to participate: This study was conducted in accordance with ethical standards. The Medical Ethics Committee approved the study procedure of Shahid Beheshti University of Medical Sciences (IR.SBMU.PHNS.REC.1399.132). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with many aspects of disturbed metabolic health. MASLD encompasses a wide spectrum of liver diseases, ranging from isolated steatosis to metabolic dysfunction-associated steatohepatitis (MASH), up to fibrosis, cirrhosis, and ultimately hepatocellular carcinoma. Limited noninvasive diagnostic tools are currently available to distinguish the various stages of MASLD and as such liver biopsy remains the gold standard for MASLD diagnostics. We aimed to explore whether the plasma lipidome and its variations can serve as a biomarker for MASLD stages., Methods: We investigated the plasma lipidome of 7 MASLD-free subjects and 32 individuals with MASLD, of whom 11 had MASH based on biopsy scoring., Results: Compared with the MASLD-free subjects, individuals with MASLD had higher plasma concentrations of sphingolipids, glycerolipids, and glycerophospholipids. Only plasma concentrations of ceramide-1-phosphate C1P(d45:1) and phosphatidylcholine PC(O-36:3), PC(O-38:3), and PC(36:2) differed significantly between presence of MASH in individuals with MASLD. Of these lipids, the first three have a very low relative plasma abundance, thus only PC(36:2) might serve as a biomarker with higher plasma concentrations in MASLD individuals without MASH compared to those with MASH., Conclusions: Plasma lipids hold promise as biomarkers of MASLD stages, whereas plasma PC(36:2) concentrations would be able to distinguish individuals with MASH from those with MASLD without MASH., Competing Interests: Declarations. Ethical approval: The study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Review Board (or Ethics Committee) of the Amsterdam University Medical Centers (AUMC) and the Maastricht University Medical Center (MUMC+). Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare single-gene X-linked immunodeficiency disease caused by mutations in the forkhead box protein 3 (FOXP3) gene. The typical clinical manifestations of IPEX mainly include severe atopic dermatitis, insulin-dependent type 1 diabetes mellitus, and intractable diarrhea., Case Presentation: Here, we report a boy with intractable diarrhea diagnosed with early-onset IPEX syndrome due to the c.434C > T (p.Ala145Val) mutation in exon 4 of the FOXP3 gene. The patient experienced intractable diarrhea and severe weight loss, and his clinical symptoms could not be alleviated by conventional supportive and anti-infection treatment. Sirolimus, an immunosuppressant, preferentially inhibits effector T cells while allowing the proliferation of Tregs and is used to treat IPEX patients and alleviate intractable diarrhea., Conclusion: We reviewed the literature on the use of sirolimus for the treatment of IPEX syndrome over the past two decades., Competing Interests: Declarations. Ethics approval and consent to participate: This study was in compliance with the Helsinki Declaration and was approved by the Ethical Review Board of Shanghai Children’s Hospital. Consent for publication: The parents of the patients consented to the publication of the case and any accompanying images with written consent. Written informed consent was obtained from the parents of the patients for the publication of this study. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Pharmacologic prophylaxis for gastric ulcer is commonly prescribed in patients hospitalized in the intensive care unit (ICU). The aim of the study was to assess the current prevalence and risk factors for gastric mucosa lesion in ICU patients receiving standard pharmacologic prophylaxis undergoing endoscopy for percutaneous gastrostomy implantation., Methods: Patients hospitalized in the mixed medical-surgical ICU undergoing percutaneous endoscopic gastrostomy (PEG) were analyzed. We excluded patients receiving either no or high doses of intravenous proton pump inhibitor (PPI), only patients receiving standard doses of PPI were included. Data retrieved from the electronic medical records included: demographics, risk factors for gastric mucosa lesion (use of stimulants, comorbidities, medications, treatment methods in the ICU, laboratory derangements) and endoscopic findings. The study compared a group of patients with gastric mucosa lesions (cases) vs. patients without gastric mucosa lesions (controls). Inter-group comparisons between cases and controls were performed. Depending on the type of distribution continuous variables were assessed using two-sample t-test or Mann-Whitney test, whereas categorical variables with Chi-squared or Fisher exact test. Odds ratio (OR) with 95% confidence interval (95% CI) were calculated. Statistical significance was assumed at p < 0.05., Results: Patients with no prophylaxis (n = 8) or receiving high doses (> 40 mg per day) of proton pump inhibitor (n = 2) were excluded. There were 182 patients receiving standard intravenous dose of PPI, 63 (34.6%) women and 119 (65.4%) men, with median age 61.5 (interquartile range IQR 46.0-70.0) years. Majority of patients (n = 169, 92.9%) were receiving pharmacological prophylaxis for venous thromboembolism. There were 53 (29.1%) patients with gastric mucosa lesion. The only risk factor that was significantly different between cases and controls was history of gastric ulcer (p = 0.04) with OR 3.8 (95% CI 1.1-12.5; p = 0.03)., Conclusions: Majority of various risk factors for gastric ulceration may not predict gastric mucosa lesion in ICU patients receiving standard pharmacological prophylaxis undergoing endoscopy for PEG implantation. We found that history of gastric ulcer may be a risk factor for gastric ulceration in the ICU patients. Patients with history of gastric ulcer might benefit from higher than standard doses of anti-ulcer medication when hospitalized in the ICU., Competing Interests: Declarations. Ethics approval and consent to participate: Due to retrospective character of the study, the Bioethics Committee of Medical University of Silesia decided that the study does not require an ethical review and waived the requirement for an informed consent (Ethics Committee of Medical University of Silesia in Katowice decision number: PCN/CBN/0022/KB/292/21). The study was conducted according to the principles expressed in the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Mushrooms, an integral component of human diets, range from esteemed delicacies to potentially lethal toxins. The risk of severe poisoning from misidentified species, poses a significant challenge. For clinicians, recognizing mushroom poisoning amidst nonspecific symptoms and determining the specific mushroom ingested are critical yet complex tasks. Additionally, climate change affects the distribution and proliferation of mushroom species, potentially heightening the risk of exposure to toxic varieties. The identification of mushroom intoxication is critical for appropriate treatment. Poisoning with highly toxic species, such as Amanita phalloides (death cap), can result in acute liver and kidney failure. Considering the limited therapeutic options currently available for acute liver failure, we investigated the application of plasmapheresis, a procedure involving the replacement of the patient's plasma with donor plasma, as a potential intervention to improve clinical outcomes in severe cases of mushroom poisoning., Methods: This study aimed to assess the trends and treatment outcomes of mushroom poisoning cases from 2005 to 2022, with a particular focus on the number of incidents and the potential impacts of climate change. We undertook a retrospective monocentric cohort study, evaluating 43 patients with mushroom poisoning. The study focused on identifying the variety of mushrooms involved, including psychotropic, spoiled, inedible, or toxic species, and closely examined patients with elevated transaminases indicative for liver damage. To assess clinical outcomes, we evaluated several aspects, including hepatic encephalopathy and other symptoms. Additionally, we monitored blood analysis results through serial measurements, including transaminases, bilirubin, INR, and creatinine levels. Furthermore, we explored the impact of climate changes on the incidence of mushroom poisoning., Results: While the incidence of mushroom poisonings remained relatively stable during the first eight years of the study period, it nearly doubled over the past nine years. Nine distinct mushroom types were documented. The study showed no change in season patterns of mushroom poisonings. In cases of severe liver damage accompanied by coagulopathy, plasmapheresis was utilized to replace deficient clotting factors and mitigate the inflammatory response. This intervention proved effective in stabilizing coagulation parameters, such as the international normalized ratio (INR) Plasmapheresis was performed until the INR reached stable levels, preventing the occurrence of severe bleeding complications. In instances where liver failure was deemed irreversible, plasmapheresis functioned as a bridging therapy to manage bleeding risks and to stabilize the patient while awaiting liver transplantation., Conclusion: The findings underscore the need for heightened awareness among healthcare professionals regarding mushroom poisoning and emphasize the importance of considering climate change as a factor that may alter mushroom distribution and toxicity. Additionally, this study highlights the potential of plasmapheresis in managing severe cases., Competing Interests: Declarations. Ethics approval and consent to participate: The studies involving human participants were reviewed and approved by Ethics Committee of the University of Regensburg, Regensburg, Germany. Informed consent was obtained from all participants. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objective: Methylmalonic acidemia (MMAs) is known as a severe, complex, and lethal disorder of methylmalonate and cobalamin. The patients with MMA may have developmental, neurological, and metabolic disorders such as liver disease. Here, we aim to evaluate 6 Iranian patients suspected to MMA disorder., Study Design: We will provide genetic results, biochemical analysis and treatment for these patients. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) and variant screening in probands by whole exome sequencing (WES) were performed., Results: A total of six homozygous variants were identified, including five previously identified variants and one novel variant, in the two MMA-causing genes as follows: c.577G > C, c.290 + 69G > T, c.662T > A, c.290 + 69G > T of MMAB, and c.100dupA, c.394 C > T of MMACHC. Sanger sequencing confirmed the identified variants. Additionally, metabolomics data analysis reliably identified elevated C3 and MMA levels, as well as abnormalities in the amino acid profile, indicating the presence of pathogenic variants., Conclusions: Our findings expand the global spectrum of genotypes in MMA. While WES, combined with metabolomics and biochemical analysis, offers valuable insights for accurate diagnosis and subtyping of MMA, it is most beneficial in complex cases where clinical findings are unclear., Competing Interests: Declarations. Human ethics and consent to participate: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Bioethics Committee of the Medical University of Shiraz, Iran (No. IR.SUMS.REC.1400.912). Informed consent was obtained from legal guardians. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background and Aim: The association between biliary disorders with weight reduction enhanced by GLP-1RAs was observed frequently, nevertheless, the relative risk of the clinically relevant cholelithiasis was not specified clearly among different GLP-1RAs., Methods: 308 patients with type 2 diabetes mellitus (T2D) were recruited and divided into 4 groups; liraglutide, dulaglutide, semaglutide, versus control group; comprised of 69, 76, 71, and 92, respectively. Clinical history, examination, laboratory, and radiology tests were implemented., Results: Cholelithiasis significantly associates GLP1-RAs (p = 0.033). Overall cholelithiasis was evident in 31.2% of our participants. Symptomatic cholelithiasis prevails in 60.4% of patients with cholelithiasis. Symptomatic complicated cholelithiasis prevailed in 33.3%; distributed in 28.1%, 28.1%, 21.9%, and 21.9% in liraglutide, semaglutide, dulaglutide, and control groups, respectively. Meanwhile, symptomatic uncomplicated cholelithiasis was observed in 27.1%; distributed in 34.6%, 30.8%, 15.4%, and 19.2% in Liraglutide, semaglutide, dulaglutide, and control groups, respectively. Asymptomatic cholelithiasis was noted in 36.8%, 21.1%, 10.5%, and 31.6% of patients with dulaglutide, semaglutide, liraglutide, and control groups, respectively. Specifically, 81.1%, 68%, and 44% of patients with liraglutide, semaglutide, and dulaglutide experienced symptomatic cholelithiasis. The relative risk of cholelithiasis was 1.2, 1.3, and 1.4 in liraglutide, dulaglutide, and semaglutide with number needed to harm of 17.25, 14.69, and 10.96, respectively. The relative risk of symptomatic cholelithiasis was 1.6, 0.9, and 1.4 in liraglutide, dulaglutide, and semaglutide with number needed to harm of 3.14, 16.67, and 5.56, respectively., Conclusion: Liraglutide was associated with the highest risk of clinically relevant cholelithiasis than semaglutide, and dulaglutide in patients with T2D., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Institutional Review Board for Clinical Research committee of Mansoura University with approval code (No. R.22.10. 1897.R1) and with the IRB committee, Al Yousif Hospital, Alkhobar, Saudi Arabia, (AYH IRB: 02/03/2023). All procedures performed were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and later versions.Written informed consent was approved by the IRB and signed by all participants before enrolment. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Hereditary spherocytosis is a rare genetic disorder of the red blood cell membrane that is characterized by anemia, jaundice, and splenomegaly; however, in the absence of family history and with unusual clinical presentation, the diagnosis might not be made until later in life., Case Presentation: Here, we present a challenging case of genetically proven hereditary spherocytosis that involves the SPTB gene in a 23-year-old female patient from Ethiopia who had repeated medical visits for episodic jaundice and hepatosplenomegaly, with unusual features of conjugated hyperbilirubinemia, pancytopenia, normal reticulocyte count, and lack of family history, where the delay in diagnosis led to several complications. The patient was successfully managed with simultaneous splenectomy and cholecystectomy., Conclusion: This case underscores the importance of a thorough clinical examination, spending the time to review a case periodically without assuming the initial diagnosis is correct, and maintaining a healthy skepticism of inconsistent data to prevent misdiagnosis and mistreatment. The diagnostic delay highlights the need for increased awareness and familiarity with diagnostic modalities of hereditary spherocytosis among healthcare providers in Ethiopia., Competing Interests: Declarations. Ethical approval: Ethical approval from the affiliated institution is not required for a single case report. Consent for publication: Written informed consent was obtained from the patient for the publication of this case report and any accompanying images. A copy of written consent is available for review by the Editor-in-Chief of this journal. Conflict of interest: The authors have no relevant conflicts of interest., (© 2024. The Author(s).)

Background: Despite adequate treatment, a subgroup of patients with inflammatory bowel disease (IBD), including Crohn`s disease and ulcerative colitis, have persistent gastrointestinal symptoms that are not always related to mucosal damage. Recently, two autoantibodies, anti-CdtB and anti-vinculin, were validated as post-infectious IBS (PI-IBS) markers, however there is limited evidence of its diagnostic role in IBD population., Methods: Patients with more than 3 bowel movements/day and indication of colonoscopy were enrolled. Samples were collected at the time of colonoscopy for assessment of serum levels of anti-CdtB and anti-vinculin antibodies., Results: A total of 160 subjects were included in 4 groups: active IBD (n = 44); quiescent IBD and chronic diarrhea IBD-IBS (n = 25); predominant-diarrhea IBS (n = 45) and controls (n = 46). The mean value of the optical density for anti-CdtB was 1.2 ± 0.65 in group 1, 1.27 ± 0.64 in group 2, 1.49 ± 0.47 in the group 3 and 1.6 ± 0.68 in group 4, p = 0.012. For anti-vinculin, optical densities were: 1.34 ± 0.78 in group 1, 1.46 ± 0.92 in group 2, 1.31 ± 0.79 in group 3 and 1.41 ± 0.86 for controls (p = 0.875). Using a cut-off of 1.56 for anti-CdtB, the positivity between groups was n = 10 (22.7%) in group 1, n = 9 (34.6%) in group 2, 19 (43.2%) in group 3, 21 (45.7%) in group 4 (p = 0.106). The positivity of anti-vinculin using a cut-off of 1.6 was n = 18 (40.9%) in group 1, n = 11 (42.3%), n = 15 (34.1%), n = 22 (47.8%) (p = 0.622)., Conclusions: Our findings show that anti-CdtB and anti-vinculin could not identify IBD-IBS patients or discriminate IBS-D from healthy controls., Competing Interests: Declarations. Ethics approval and consent to participate: The study was approved by the Institutional Ethics Review Board of Clinics Hospital, University of São Paulo School of Medicine. Written informed consent was obtained from patients before enrollment. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objective: This study investigates correlates of maternal leukocyte telomere length (LTL) in the immediate postpartum period using a cross-sectional study design from an existing prospective longitudinal birth cohort of primarily Latina women. The study focuses on the role of maternal health and dietary habits in pregnancy and maternal education level and LTL at delivery., Study Design: Latina mothers were recruited during the immediate postpartum period prior to 24 h at two San Francisco hospitals and dried blood spots were collected for LTL analysis via quantitative polymerase chain reaction (qPCR). We used multivariable linear regression models to determine independent predictors of maternal LTL during the postpartum period., Results: In multivariable regression models, increasing maternal age was associated with shorter LTL during the immediate postpartum period (Coeff - 0.015; p < 0.01) whereas having a high school diploma was associated with longer LTL versus not having graduated from high school (Coeff 0.12; p < 0.01)., Conclusion: Maternal education level as a potential marker of exposure to life stressors and socioeconomic status was associated with maternal LTL after adjusting for age and other potential confounders in women of reproductive age., Competing Interests: Declarations. Ethics approval and consent to participate: All participants provided written informed signed consent and the study was approved by the UCSF Institutional Review Board (IRB). Consent for publication: N/A. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: The vitamin D binding protein (DBP) plays a critical role in both innate and adaptive immune systems, participating in several clinical conditions, including coronavirus disease 2019 infection severity, and mortality rate. The study aimed to investigate the correlation between rs7041 and rs4588 polymorphisms in the DBP gene and Coronavirus Disease-2019 (COVID-19) severity and mortality, in patients of Suez Canal University Hospitals in Ismailia, Egypt., Methods: A case-control study enrolled 220 individuals; 140 COVID-19 patients and 80 healthy controls. Serum 25(OH) vitamin D levels were determined by the enzyme-linked immunosorbent assay (ELISA), and rs7041 and rs4588 polymorphisms of the DBP gene were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)., Results: The study found that both groups had vitamin D deficiency, which was considerably lower in the COVID-19 patients group compared to controls. Among COVID-19 patients, there was a significant difference in vitamin D levels according to the disease severity indicating that vitamin D levels can be used as predictors of COVID-19 severity. Negative significant correlations between genetic variants rs4588 CA genotype and genetic variants rs7041 TT genotype and COVID-19 prevalence (p = 0.006 and 0.009 respectively) were proved. No significant correlations between all the genetic variants of both rs4588 and rs7041 and COVID-19 severity (p > 0.05). Positive significant correlations between both genetic variants rs4588 CA genotype and genetic variants rs7041 TG genotype and COVID-19 mortality (p = 0.029 and 0.031 respectively)., Conclusion: vitamin D deficiency increased the severity of COVID-19. The DBP polymorphism correlated with vitamin COVID-19 prevalence and mortality., Competing Interests: Declarations. Human ethics and consent to participate: Ethical approval was obtained from the Research Ethics Committee of the Faculty of Medicine, Suez Canal University, Egypt, #5088. All subjects were informed and gave their voluntary, written informed consent. It is declared that: All methods were carried out in accordance with relevant guidelines and regulations. It was performed according to the recommendations of Good Clinical Practice and the Declaration of Helsinki (2013). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Climate change in the upcoming years will raise the health burden of zoonotic parasites. As a liver fluke, Fasciola depends on certain climate conditions to complete its life cycle and is significantly influenced by climate changes. We aimed to investigate the relationship between the increasing prevalence of human fascioliasis and climate changes in Upper Egypt., Methods: Records of Fasciola cases in Assiut Governorate in Upper Egypt were evaluated between September 2018 and March 2023. The annual and monthly climate parameters of the region's temperature and humidity acquired from ERA5 and FLDAS were investigated between 2000 and 2023., Results: A total of 303 patients were included. The mean age was 33.9 ± 17.4 years; 57.1% were females, and the majority were rural residents. Positive correlations were found between temperature and the recorded cases in 2018, 2020, 2021, and 2022 (r = 0.92, 0.41, 0.61, and 0.60, respectively). In 2018 and 2022, humidity and Fasciola frequency had a significant positive correlation (r = 0.97 and 0.49, respectively). An outbreak of fascioliasis was recorded in September 2018, coinciding with the peak temperature and high humidity levels, exceeding the average climatology range from 2000 to 2017. The recorded cases exhibited a seasonal pattern, with peaks in hot, humid summer and autumn., Conclusion: The rise of human fascioliasis in Upper Egypt is influenced by local climate characteristics. A climate-based map of Fasciola distribution using forecast risk models is needed to predict future outbreaks and for better control., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: The study was approved by the Ethics Committee at the Central Directorate of Research and Health Development and Review in the Ministry of Health and Population, Egypt. The informed consent of the participants was waived due to the study’s retrospective nature. The study was conducted following the Helsinki Declaration., (© 2024. The Author(s).)

Background: Primary breast hydatid cyst is an exceedingly rare manifestation of echinococcosis, with an incidence of less than 0.27% among all hydatid cyst cases., Case Report: This report presents a unique case of a 51-year-old multiparous female who initially presented with a painless left breast mass. Initial imaging studies, including ultrasonography and mammography, revealed a 4.5 × 4 cm cyst classified as BI-RADS 3. The cyst was initially managed with fine-needle aspiration and conservative treatment. However, it recurred twice over a six-month period, necessitating surgical excision. Preoperative laboratory work ups revealed eosinophilia, a finding initially overlooked but later recognized as significant. Histopathological examination of the excised specimen confirmed the diagnosis of a hydatid cyst. Post-surgical management included albendazole therapy, regular imaging follow-ups, and patient education on hygiene practices to prevent reinfection., Conclusion: This case highlights the importance of considering parasitic etiologies in the differential diagnosis of breast masses, particularly in endemic regions. It also underscores the value of a multidisciplinary approach in managing such rare cases. The unexpected diagnosis of a primary breast hydatid cyst in this case serves as a reminder of the diverse presentations of echinococcosis and the need for heightened clinical suspicion in atypical breast lesions., Clinical Trial Number: Not applicable., Competing Interests: Declarations. Ethics approval and consent to participate: This case report was conducted in full adherence to the highest ethical standards in medical research and publishing. The study meticulously followed the ethical guidelines set forth by the institutional and national research committees, as well as the principles outlined in the 1964 Helsinki Declaration and its subsequent amendments. It is important to note that this article does not include any studies involving animals. The authors have taken extensive measures to protect the patient’s privacy and maintain confidentiality. All identifying information, including the patient’s name, initials, and other potentially identifiable details, have been omitted from this report. Furthermore, no images that could potentially identify the patient have been included in this publication.The preparation of this case report encountered no ethical challenges. Throughout the process, the patient’s autonomy and privacy were consistently respected. The medical history and treatment details have been presented with the utmost discretion and sensitivity, ensuring that the patient’s dignity is preserved while maintaining the scientific value of the report. Consent for publication: Each author listed assumes responsibility for the overall integrity of the work and has provided consent for the publication of this version. Consent statement: A written informed consent was obtained from the patient to publish this report in any medical journals. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

A research protocol is a document that outlines the proposed research idea and is submitted to funding agencies, institutions, or journals for approval. Writing a research protocol represents a challenge, particularly for early-career researchers. In this guide, we aim to provide detailed guidance with the key components and offer practical tips for crafting a research protocol in line with the various study designs. Specifically, the structure of a research protocol should contain the following items: (1) a title that is specific, catchy, and impressive within the word limitation; (2) an abstract that briefs the critical points of the study; (3) an introduction highlighting the study context from broad to narrow and defining the knowledge gap; (4) a justification underlining the significance of the proposed study; (5) Specific, Measurable, Attainable, Relevant, and Time-bound (SMART) objective(s) and aim(s); (6) a methodology covering seven sub-items, including [i] study design and settings, [ii] study subjects, [iii] sample size calculation and sampling, [iv] participants recruitment and follow-up, [v] questionnaire development, [vi] potential variables and outcomes, and [vii] data analysis plan; (7) dissemination of the results; (8) ethics and conflict of interests; (9) budgets analysis/ funding disclosure; and (10) references. This guide will give an overview of these steps and provide clear and concise tips on how to successfully draft a scientific protocol. With careful planning and appropriate guidance, it is possible to develop a well-structured and compelling protocol to obtain approval for the conduction of the study or funding from agencies, institutions, or organizations., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing of interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Gastrointestinal (GI) cancers have heavily burdened public health. Few studies reported GI cancer burden among adolescents and young adults (AYA). To address this gap, we explored the burden of GI cancer among people aged 15-39., Methods: We retrieved data from the Global Burden of Disease Study 2019 Data Resources. The average annual percent change (AAPC) of rates was calculated by linear regression analysis of the natural logarithm. Bayesian age-period-cohort model was applied to predict the future burden., Results: In 2019, there were 171,857 (95% uncertain interval [95% UI]: 157,092-187,974) new GI cancer cases with a rate of 5.79/100,000 (95% UI: 5.29-6.33) and 91,033 (95% UI: 83,156-99,399) deaths at a rate of 3.07/100,000 (95% UI: 2.80-3.35) among AYA. The number of prevalent cases and disability-adjusted life years (DALYs) were 722,573 (95% UI: 660,806-789,476) and 5,151,294 (95% UI: 4,706,065-56,188,77), with rates of 24.35/100,000 (95% UI: 22.27-26.60) and 173.57/100,000 (95% UI: 158.57-189.32) respectively. The overall rates of mortality (AAPC = -1.281, p < 0.001) and DALY (AAPC = -1.283, p < 0.001) of GI cancers declined during the past 30 years, while the incidence rate (AAPC = -0.270, p = 0.074) remained stable and the prevalence rate (AAPC = 1.066, p < 0.001) increased. The burden of colorectal cancer (CRC) and pancreatic cancer increased, while those of stomach cancer (SC) and liver cancer (LC) declined. Among the 21 GBD regions, East Asia exhibited the highest burden, while within the five SDI regions, high-middle SDI locations showed the highest rates across all four indicators. CRC, SC, and LC emerged as the primary culprits, attaining a position within the top ten absolute DALYs for all AYA cancers. There were predicted to be 315,792 new cases and 174,068 deaths of GI cancers among AYA in 2040., Conclusions: Despite the decrease in mortality and DALY rates of GI cancers among AYA, they remain prevalent. The burden varied with locations, SDI levels, sexes, and cancer types. Sufficient attention and multi-party cooperation are needed to control the widespread public health issue., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: This study evaluated the impact of contrast-enhanced ultrasonography (CEUS) combined with CT or MRI fusion imaging on percutaneous radiofrequency ablation (RFA) outcomes for hepatocellular carcinoma (HCC) inconspicuous on conventional ultrasonography (US)., Methods: Patients were categorized into US-inconspicuous (USI) and US-conspicuous (USC) groups based on US imaging. The parameters of viable HCCs ⎯ including diameter, location, and RFA efficacy ⎯ were compared between USI and USC groups. Moreover, the breathing fusion imaging errors were measured. The differences in technical success, technical efficacy, local tumor progression, new tumor occurrence, and overall survival rate between USI and USC groups were analyzed., Results: Sixty-five patients with 106 lesions were included. CEUS showed high consistency with CT/MRI but revealed larger diameters (p < 0.001) and more feeding arteries (p = 0.019) than CT/MRI. Breathing fusion imaging errors averaged 17 ± 4 mm, significantly affecting lesions in segments II, III, V, and VI (p < 0.001). The USI group had more lesions ablated per patient in a single RFA procedure (p = 0.001) than the USC group. No significant differences were observed in technical success rate, technical efficacy rate, local tumor progression rate, and overall survival rate between the two groups., Conclusions: CEUS combined with fusion imaging provides detailed information on viable HCCs and their feeding arteries. CEUS-guided RFA avoids fusion imaging errors and achieves comparable efficacy in both US-conspicuous and US-inconspicuous HCCs., Competing Interests: Declarations. Ethics approval and consent to participate: The current study was approved by the institutional ethics review board of Xiamen Chang Gung Hospital. Informed consent for conducting this study was waived due to its retrospective nature. The authors declare that this report does not contain any personal information that could lead to identification. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Clinical trial number: Not applicable., (© 2024. The Author(s).)

Background: Switching to systemic therapy after transarterial chemoembolization (TACE) refractoriness is more inclined to preserve liver function and decrease disease progression. Hence, we conducted a comparison between the advantages of sorafenib therapy and the continuation of TACE in patients with intermediate-stage hepatocellular carcinoma (HCC) who developed TACE refractoriness., Methods: This retrospective cohort work involved 1,200 patients with HCC who received TACE therapy at our institution between January 2018 and December 2022. Out of these, a total of 436 participants were determined to be resistant to TACE treatment throughout their clinical progression. Out of them, 271 were finally included and categorized into two groups: (1) patients who shifted from TACE to sorafenib, and (2) patients who maintained TACE treatment. The study assessed the overall survival (OS) and time to disease progression (TTDP) of patients who were resistant to TACE, comparing both groups based on when they achieved Child-Pugh C or acquired advanced-stage HCC., Results: Following confirmation of refractoriness to TACE therapy, 163 opted to continue with TACE (TACE group), whereas 108 shifted to sorafenib treatment (sorafenib group). The median TTDP was 23.36 months, while the median OS was 25.3 months, in the sorafenib group, and 11.6 and 14.2 months, correspondingly, in the TACE group (p = 0.0001)., Conclusion: Switching to sorafenib treatment significantly improved OS and TTDP in patients with intermediate-stage HCC who were refractory to TACE. These finding highlights sorafenib's potential as an effective alternative for managing disease progression in patients unresponsive to TACE, offering a valuable treatment option in this challenging clinical scenario., Competing Interests: Declarations. Institutional review board statement: The work was reviewed and permitted (IRB approval number (NLI IRB 00298/2022) by the institutional review board of National Liver institute (NLI IRB 00003413), Menoufia University, Egypt. Informed consent statement: All subjects submitted a written informed consent for their therapy Conflict-of-interest statement: All authors have nothing to disclose. Data sharing statement: No other data are available. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Effective screening for colorectal cancer (CRC) enables earlier diagnosis and intervention to improve patient survival., Methods: In this study, we prospectively conducted a blood-based CRC screening program for community residents in Hanjiang District, Yangzhou City, and evaluated the screening efficacy of a blood-based multi-locus DNA methylation assay (ColonAiQ). The ColonAiQ-positive rate and colonoscopy participation rate of the population, detection rate of intestinal lesions, and positive predictive value (PPV) of CRC and advanced adenoma (AA) were calculated, and the associated factors were explored., Results: A total of 105,285 participants were enrolled from January 2021 to December 2022, all of whom completed the ColonAiQ assay, yielding a positive rate of 6.42% (6759/105,285). The colonoscopy compliance rate was 48.56% (3282/6759). Intestinal lesions were detected in 1773 individuals (54.02%), including 63 cases of CRCs (predominately early-stage), 1195 adenomas (441 cases of AAs), 327 polyps, and 188 other benign lesions. CRC patients exhibited higher ColonAiQ scores and more positive loci compared to healthy individuals. The PPVs were 1.92% for CRC and 13.44% for AA. Among participants, 66,121 (62.8%) completed questionnaires graded by the Asia-Pacific Colorectal Screening score, with 12,139 (18.36%) classified in the high-risk tier. High-risk participants had a higher ColonAiQ-positive rate (11.07%) and PPVs for CRC (3.46%) and AA (22.18%). Factors associated with increased detection rates for CRC and AA included male gender, older age, a history of alcohol consumption, and prior polyps., Conclusions: Our study demonstrated that ColonAiQ assay effectively identifies high-risk population. These findings strongly suggest that the ColonAiQ assay represents a promising strategy for the early detection of CRC and AA in individuals at average risk., Trial Registration: Registered at ClinicalTrials.gov (NCT05336539)., Competing Interests: Declarations. Ethics approval and consent to participate: Human samples and participation in the study have been done according to the Declaration of Helsinki. Written consent was obtained from all participants and this study was approved by the Medical Ethics Committee of National Center for Chronic and Non-Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention (No. 202322). Consent for publication: Not applicable. Competing interests: YZ, HL, YS, YL, HJ, QY, CW, WP, FL, HY, and RL report them as employees of Singlera Genomics. RL reports stock ownership in Singlera Genomics and is an employee of Singlera Genomics., (© 2024. The Author(s).)