bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated single-cell RNA sequencing reveals the tumor heterogeneity and microenvironment landscape during liver metastasis in adenocarcinoma of esophagogastric junction
Authors: Xu Junrui , Sadiq Ussama , Zhao Wangruizhi , Xia Hengbo , Liu Yiwei , Zhang Renquan , Xu Aman 
Published: January 2025

BackgroundAdenocarcinoma of the esophagogastric junction (AEGJ) is a highly aggressive tumor that frequently metastasizes to the liver. Understanding the cellular and molecular mechanisms that drive this process is essential for developing effective therapies.MethodsWe employed single-cell RNA sequencing to analyze the tumor heterogeneity and microenvironmental landscape in patients with AEGJ liver metastases. This approach enabled us to characterize the diverse cell populations involved in the liver metastatic process.ResultsOur analysis revealed a significant involvement of fibroblasts and mural cells in AEGJ liver metastasis. We identified a specific fibroblast type in AEGJ liver metastasis and observed distinct gene expression patterns between adenocarcinoma of the esophagogastric junction and other stomach adenocarcinomas. Our study demonstrated high expression of the SFRP2 gene in pericyte cells during the liver metastasis of AEGJ. The incorporation of GEO, TCGA, and immunofluorescence staining of SFRP2 expression enhanced our study. High expression of SFRP2 in pericytes may influence vascular stability and angiogenesis through the Wnt pathway.ConclusionOur study provides novel insights into the cellular interactions and molecular mechanisms that underlie AEGJ liver metastasis. Targeting the identified subtype of fibroblasts or influencing SFRP2 gene expression in pericytes may offer new therapeutic strategies for combating this aggressive tumor.
Coexistence of immunoglobulin G4-related kidney disease and acute hematogenous disseminated pulmonary tuberculosis: a case report
Authors: Zhou Fangfang , Chu Hanqing , Xu Youjun , Zhang Yena , Tan Kuibi , Ge Jinxia , Shao Ningjun , Luo Qun 
Published: January 2025

BackgroundImmunoglobulin G4-related disease (IgG4-RD) is an immune-mediated fibrous inflammatory disease. Recently, an association between IgG4-RD and tuberculosis (TB) has been reported.Case summaryWe report a 56-year-old man complaining of a cough and poor appetite for 2 months and oliguria for 1 day. The patient was diagnosed with TB due to a manifestation of lymphatic TB and the radiological alterations of acute miliary pulmonary TB. He also presented with greatly elevated serum creatinine, non-albumin proteinuria, immunoglobulin subgroup IgG4, and immunoglobulin free light chain (FLC) levels. A diagnosis of IgG4-RKD was suggested by a renal biopsy. We then administered the patient glucocorticoid and anti-TB treatment for 4 months. The patient’s renal function was completely restored and the manifestations of TB were alleviated.ConclusionThe necessity and complexity of differential diagnosis in patients with coexisting IgG4-RD and TB remains challenging. Early recognition and timely treatment are important for averting its progression. Long-term monitoring is required to assess for recurrence of IgG4-RD and TB activity.
ESAT-6 protein suppresses allograft rejection by inducing CD4+Foxp3+ regulatory T cells through IκBα/cRel pathway
Authors: Huang Xiaofei , Zeng Yuqun , Lin Jingru , Liu Huazhen , Liang Chun-Ling , Chen Yuchao , Qiu Feifei , Bromberg Jonathan S. , Dai Zhenhua 
Published: January 2025

BackgroundMaintenance immunosuppression is required for suppression of alloimmunity or allograft rejection. However, continuous use of immunosuppressants may lead to various side effects, necessitating the use of alternative immunosuppressive drugs. The early secreted antigenic target of 6 kDa (ESAT-6) is a virulence factor and immunoregulatory protein of mycobacterium tuberculosis (Mtb), which alters host immunity through dually regulating development or activation of various immune cells. ESAT-6 may be a potential alternative immunosuppressant that could be utilized to suppress allograft rejection although it remains unknown whether ESAT-6 actually regulates alloimmunity.MethodsIn this study, murine skin or heart allotransplantation was performed to determine the effects of ESAT-6 protein on allograft survival. Flow cytometric analyses were conducted to quantify CD4+Foxp3+ Tregs, while immunohistochemistry was carried out to observe allograft immunopathology. Western blotting was used to detect IĸBα/c-Rel signaling during Treg induction. Finally, CD4+CD25- conventional T cells were cultured to induce Tregs and their proliferation.ResultsHere we found that ESAT-6 significantly extended murine skin and heart allograft survival, alleviated CD3+ T cell infiltration and increased Foxp3+ Tregs in an allograft. ESAT-6 augmented the percentage of CD4+Foxp3+ Tregs, whereas it decreased the frequency of Th1 and CD4+/CD8+ effector T cells in spleen and lymph nodes (LNs) posttransplantation. ESAT-6 also induced CD4+Foxp3+ Tregs from CD4+CD25- T cells in vitro by activating IĸBα/c-Rel signaling pathway, whereas inhibition of c-Rel signaling blocked Treg induction. Moreover, it suppressed conventional CD4+CD25- T cell proliferation in vitro in the absence of antigen-presenting cells (APCs), with an increase in IL-10 and decrease in IFN-γ production. On the other hand, it did not significantly alter DC maturation after allotransplantation.ConclusionThus, ESAT-6 suppresses alloimmunity and inhibits allograft rejection by inducing CD4+Foxp3+ Tregs through IĸBα/c-Rel signaling pathway.
Predictive factors for clinical cure in the treatment of HBeAg(−) chronic hepatitis B or compensated cirrhosis: a prospective observational study
Authors: Lv Yan-Qing , Guo Ru-Hua , Liu Kun-Yu , Li Jia-Jie , Ji Hui-Fan 
Published: January 2025

BackgroundSequential or combined treatment with nucleos(t)ide analogs (NAs) and pegylated interferon alpha-2b (Peg-IFN-α-2b) can improve the clinical cure rate. However, its clinical application is limited due to the adverse reactions associated with IFN.MethodsA multi-center prospective observational study was conducted involving 59 NAs-treated chronic hepatitis B (CHB) patients who were treated with a combination therapy of NAs and Peg-IFN-α-2b for 48 weeks. Another 327 NAs-treated patients received NAs monotherapy for 48 weeks. At the end of the treatment, patients were classified into either the clinically cured group or the non-clinically cured group based on clinical efficacy. The study aimed to analyze the clinical cure rate and the predictive factors.ResultsAfter propensity score matching (PSM), a total of 104 patients were included in the exposure and the control groups. After 48 weeks of treatment, 13 patients in the exposed group achieved clinical cure, with a cure rate of 25%. In contrast, in the control group was 1.92%. The clinical cure rate was greater in the population with CHB or compensated cirrhosis treated with sequential or combined Peg-IFN-α-2b and NAs than in the control group (p &lt; 0.001). Patients treated with Peg-IFN-α-2b were divided into a clinical cure group and a non-clinical cure group for single-factor regression and multi-factor binary logistic regression. The results showed that baseline qHBsAg [relative ratio (RR) = 0.997, 95%CI: [0.995, 0.999], p = 0.031] and △TBiL (RR = 0.698, 95%CI: [0.555, 0.879], p = 0.002) were independent influencing factors for achieving clinical cure in patients with CHB or compensated cirrhosis.ConclusionA lower baseline qHBsAg and decrease in TBiL at 24 weeks of treatment are independent influencing factors for achieving clinical cure. The lower the baseline qHBsAg and the higher the △TBiL levels after 24 weeks of treatment, the higher the probability of patients achieving clinical cure.
16S rRNA sequencing-based evaluation of the protective effects of key gut microbiota on inhaled allergen-induced allergic rhinitis
Authors: Tang Yi , She Yongchuan , Chen Danping , Zhou Yibo , Xie Dan , Liu Zhai 
Published: January 2025

IntroductionAllergic rhinitis (AR) is a common respiratory disorder influenced by various factors in its pathogenesis. Recent studies have begun to emphasize the significant role of gut microbiota in immune modulation and its potential association with the development of AR. This research aims to characterize the gut microbiota of patients with AR who are sensitized via inhalation, utilizing 16S rRNA sequencing to shed light on the pathogenesis of AR and identify potential therapeutic targets.MethodsTo achieve the study’s objectives, we compared the microbiota profiles between patients with AR and healthy controls. Microbial diversity was assessed using alpha and beta diversity indices, and differential microbiota populations were identified through Linear discriminant analysis Effect Size (LEfSe) analysis. A Least Absolute Shrinkage and Selection Operator (LASSO) regression model was employed to pinpoint key species. Additionally, PICRUSt2 was utilized to predict the functional pathways associated with these identified species.ResultsThe analysis identified a total of 1,122 common species, along with 1,803 species associated with AR and 1,739 species associated with healthy controls. LEfSe analysis revealed 20 significant discrepancies at the genus level. The LASSO regression model identified 8 key genera, including Prevotellaceae UCG-004 and Rhodococcus, which exhibited AUC values exceeding 0.7, indicating strong diagnostic potential. Furthermore, functional pathway analysis suggested that these pivotal species are involved in pathways such as L-lysine biosynthesis and photorespiration, potentially contributing to the pathogenesis of AR.DiscussionThis study identifies critical gut microbiota that could serve as potential biomarkers for allergic rhinitis, providing new insights into its pathogenesis and offering avenues for future therapeutic strategies. Further investigation into these microbiota may lead to enhanced understanding and management of AR.
Identification of crucial pathways and genes linked to endoplasmic reticulum stress in PCOS through combined bioinformatic analysis
Authors: Zhang Yan , Chen Xiujuan , Lin Yuan , Liu Xiaoqing , Xiong Xiumei 
Published: January 2025

BackgroundPolycystic ovary syndrome (PCOS) is a common endocrine and metabolic condition impacting millions of women worldwide. This study sought to identify granulosa cell endoplasmic reticulum stress (GCERS)-related differentially expressed genes (DEGs) between women with PCOS and those without PCOS using bioinformatics and to investigate the related molecular mechanisms.MethodsTwo datasets were downloaded from GEO and analysed using the limma package to identify DEGs in two groups—PCOS and normal granulosa cells. Enrichment analyses, including GO, KEGG, and GSEA, were then conducted on the DEGs. Differential immune infiltration was assessed using CIBERSORT and correlations with immune cell biomarkers were evaluated. Networks for protein-protein interactions, transcription factor-target genes, miRNA-target genes, and drug-target genes were constructed and visualized using Cytoscape to identify key hub gene nodes. Finally, key genes were analysed for differential expression and correlated.ResultsOverall, 127 co-DEGs were identified in the two datasets. Our study revealed that these DEGs were primarily associated with cell cycle arrest, p53-mediated signal transduction, drug response, and gland development, with molecular functions enriched in growth factor binding, collagen binding, and receptor protein kinase activity. GSEA revealed that the co-DEGs were primarily associated with immune and inflammatory pathways. Eleven hub genes—MMP9, SPI1, IGF2R, GPBAR1, PDGFA, BMPR1A, LIFR, PRKAA1, MSH2, CDC25C, and KCNH2—were identified through the PPI, TF target genes, miRNA target genes, and drug target gene networks.ConclusionWe identified several crucial genes and pathways linked to the onset and development of PCOS. Our findings offer a clear connection between PCOS and GCERS, clarify the molecular mechanisms driving PCOS progression, and offer new perspectives for discovering valuable therapeutic targets and potential biomarkers for the condition.
Meridional anisotropy in contrast sensitivity and visual evoked potential in adults with high myopic astigmatism
Authors: Wu Siu Sang Anthony , Leung Tsz Wing 
Published: January 2025

PurposeAstigmatism can lead to meridional amblyopia, an orientation-specific visual deficit. This study investigated the effects of astigmatism on meridional anisotropy in contrast sensitivity (CS) and steady-state visual evoked potential (ssVEP) across a range of spatial frequencies.MethodsThirty-two young adults with a best-corrected distance visual acuity of logMAR 0 or better were categorized into two groups: highly astigmatic (HAS, n = 16) with spherical-equivalent error (SE) ≥ −6.00 D and a cylindrical error (Cyl) ≥ 2.00 DC, and non-astigmatic (NAS, n = 16) with SE ≥ −6.00 D but Cyl ≤ 0.50 DC. We assessed CS using a spatial four-alternative forced-choice procedure and recorded ssVEP at spatial frequencies ranging from 0.6 to 12 cycles per degree (cpd) for horizontal and vertical gratings. The Area Under Log Contrast Sensitivity Function (AULCSF) and spatial frequency cutoff for the CS were also calculated.ResultsThe HAS group exhibited significantly lower CS for horizontal compared to vertical gratings at most spatial frequencies (p &lt; 0.045 for 0.6–6 cpd), also reflected in a lower AULCSF (p = 0.01). This meridional anisotropy in CS was absent in the NAS group for both AULCSF and individual spatial frequencies, except at 0.6 cpd (p = 0.005). Spatial frequency cutoff did not differ between orientations for either group (p &gt; 0.94). Conversely, ssVEP amplitudes were consistently lower for horizontal than vertical gratings in both groups, regardless of the presence of astigmatism (p &lt; 0.05).ConclusionMeridional anisotropy in contrast sensitivity was observed only in highly astigmatic participants, whereas meridional anisotropy in ssVEP was present in both highly astigmatic and non-astigmatic groups. This discrepancy between psychophysical and electrophysiological measures may be related to the static versus flickering nature of the stimuli and warrants further investigation.
Efficacy analysis of prophylactic hyperthermic intraperitoneal chemotherapy in patients with locally advanced gastric cancer: a retrospective study
Authors: Gong Zhijie , Zhou Liping , He Yinghao , Zhou Jun , Deng Yanjie , Huang Zudong , Wang WeiWei , Yang Qiangbang , Pan Jian , Li Yingze , Yuan Xiaolu , Ma Minghui 
Published: January 2025

PurposeThis study aims to evaluate the effectiveness and safety of prophylactic hyperthermic intraperitoneal chemotherapy (P-HIPEC) in patients with locally advanced gastric cancer (AGC) after laparoscopic radical gastrectomy. Additionally, it explores how the frequency and timing of P-HIPEC influence treatment outcomes.MethodsA retrospective analysis was conducted on 227 patients with locally AGC who underwent laparoscopic surgery at Maoming People’s Hospital from January 2016 to December 2022. Patients were stratified into the HIPEC group (n=101) and the non-HIPEC group (n=126), based on whether they received postoperative P-HIPEC. Propensity score matching (PSM) was used to adjust for baseline characteristics, facilitating a comparative analysis of survival outcomes, postoperative complications and recurrence patterns. Cox regression analysis was performed to identify prognostic factors. Furthermore, the impact of varying P-HIPEC frequencies and initiation timings was evaluated.ResultsNo significant differences in overall survival (OS) or postoperative complication rates were observed between the two groups in the original and PSM cohorts. But the disease-free survival (DFS) of the HIPEC group was significantly higher than that of the non-HIPEC group (HR 0.569; 95% CI 0.362–0.894; p = 0.013) in the PSM cohort, with 1-year, 3-year, and 5-year DFS rates showing notable improvement (77.9% vs. 69.7%, 60.1% vs. 43.0%, and 46.2% vs. 25.5%). The incidence of isolated peritoneal metastasis (PM) was significantly lower in the HIPEC group (5.3% vs. 17.3%, p = 0.039). Multivariate Cox regression analysis identified P-HIPEC as an independent protective factor for DFS. Further analysis indicated that neither the number of P-HIPEC sessions had a significant impact on OS (p = 0.388) or DFS (p = 0.735), nor did the timing of P-HIPEC initiation affect OS (p = 0.620) or DFS (p = 0.488). Likewise, different P-HIPEC frequencies or initiation timings had no significant impact on postoperative complication rates or recurrence patterns.ConclusionP-HIPEC effectively reduces the risk of postoperative PM and improves DFS in patients with locally AGC without increasing postoperative complications. However, it does not significantly impact OS. Additionally, variations in the frequency and timing of P-HIPEC initiation do not significantly affect survival outcomes, postoperative complications, or recurrence patterns.
Distinct mRNA expression profiles and miRNA regulators of the PI3K/AKT/mTOR pathway in breast cancer: insights into tumor progression and therapeutic targets
Authors: Sirek Tomasz , Król-Jatręga Katarzyna , Borawski Przemysław , Zmarzły Nikola , Boroń Dariusz , Ossowski Piotr , Nowotny-Czupryna Olga , Boroń Kacper , Janiszewska-Bil Dominika , Mitka-Krysiak Elżbieta , Grabarek Beniamin Oskar 
Published: January 2025

BackgroundBreast cancer remains a leading cause of mortality among women, driven by the molecular complexity of its various subtypes. This study aimed to investigate the differential expression of genes and miRNAs involved in the PI3K/AKT/mTOR signaling pathway, a critical regulator of cancer progression.MethodsWe analyzed tumor tissues from five breast cancer subtypes—luminal A, luminal B HER2-negative, luminal B HER2-positive, HER2-positive, and triple-negative breast cancer (TNBC)—and compared them with non-cancerous tissues. Microarray and qRT-PCR techniques were employed to profile mRNAs and miRNAs, while bioinformatic tools predicted miRNA-mRNA interactions. Statistical analysis was performed with a statistical significance threshold (p) &lt; 0.05.ResultsWe identified several upregulated genes across all subtypes, with TNBC and HER2-positive cancers showing the most significant changes. Key genes such as COL1A1, COL4A1, PIK3CA, PIK3R1, and mTOR were found to be overexpressed, correlating with increased cancer aggressiveness. miRNA analysis revealed that miR-190a-3p, miR-4729, and miR-19a-3p potentially regulate these genes, influencing the PI3K/AKT/mTOR pathway. For instance, reduced expression of miR-190a-3p may contribute to the overexpression of PIK3CA and other pathway components, enhancing metastatic potential.ConclusionOur findings suggest that the PI3K/AKT/mTOR pathway and its miRNA regulators play crucial roles in breast cancer progression, particularly in aggressive subtypes like TNBC. The identified miRNAs and mRNAs hold potential as biomarkers for diagnosis and treatment, but further validation in functional studies is required. This study provides a foundation for targeted therapies aimed at modulating this critical pathway to improve breast cancer outcomes.
Systematic review and bayesian network meta-analysis: comparative efficacy and safety of six commonly used biologic therapies for moderate-to-severe Crohn’s disease
Authors: Su Haohang , Xiao Shengwei , Liang Zhiqing , Xun Tianrong , Zhang Jinfang , Yang Xixiao 
Published: January 2025

BackgroundIn contrast to previous network meta-analysis using classical frequentist methods, we evaluated the efficacy and safety of six frequently-used biologics through a Bayesian method.MethodsWeb of Science, Scopus, CENTRAL, ClinicalTrials.gov and ICTRP were searched to collect randomized controlled trials (RCTs) in adults with moderate-to-severe Crohn’s disease, comparing Infliximab, Adalimumab, Certolizumab pegol, Ustekinumab, Risankizumab, or Vedolizumab, relative to placebo or an active comparator for induction of clinical response (two different definitions) and maintenance of clinical remission. A random-effects model was performed with rankings according to the surface under cumulative ranking curve (SUCRA) probability. Finally, we completed sensitivity and consistency analyses, and evaluated the certainty of evidence through GRADE working group guidance.ResultsWe identified 22 and 20 RCTs for induction and maintenance therapy, respectively. Infliximab combined with azathioprine was most effective for inducing clinical response in TNF (tumor necrosis factor) antagonist-naïve patients. For TNF antagonist-experienced patients, Ustekinumab (SUCRA 86.19) and Risankizumab (SUCRA 62.56) have the largest SUCRA in induction of clinical response. Risankizumab has the lowest risk of adverse events (SUCRA 84.81), serious adverse events (SUCRA 94.23), and serious infections (SUCRA 79.73) in induction therapy. Adalimumab and the 10 mg/kg regimen of Infliximab rank highest for maintaining clinical remission.ConclusionThis analysis suggests that Infliximab in combination with azathioprine may be preferred biologic agents for induction therapy in TNF antagonist-naïve patients. For TNF antagonist-experienced patients, Ustekinumab and Risankizumab may be preferred biologic agents for induction therapy. Risankizumab potentially has the lowest safety risk worth exploring in induction therapy. Adalimumab and the 10 mg/kg regimen of Infliximab have maintenance efficacy benefits for responders to induction therapy.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=458609, Identifier CRD42023458609.
Traditional uses, botanical description, phytochemistry, and pharmacological activities of Phytolacca acinosa: a review
Authors: Khalid Tooba , Chang Chieh-Wei , Ross Samir Anis , Naseer Faiza , Qadeer Abdul , Chen Chien-Chin , Rafey Hafiz Abdul 
Published: January 2025

BackgroundPhytolacca acinosa is an herbaceous herb belonging to the Phytolaccaceae family. The plant has a long history of usage in traditional medicine for treating a variety of ailments including infectious diseases, edema, inflammation, gastric, and abdominal distress. The traditional use, phytochemistry, and pharmacological properties of Phytolacca acinosa are outlined in this article.Main textTo date, few bioactive molecules have been identified and isolated from the plant, such as phytolacacinoside A, esculentoside H, jaligonic acid and esculentoside B, phytolaccanol and epiacetyl aleuritolic acid, esculentoside A, esculentoside C, esculentoside D, esculentoside T, esculentoside S, sitosterol. The literature related some of the reported ethnomedicinal uses of the plant to these compounds found in different parts of the plant.ConclusionThe in-depth knowledge about the significance of Phytolacca acinosa presented in this review may open up opportunities for research development in drug discovery and a better comprehension of the therapeutic advantages of the plant.