Background Liver fibrosis is a major contributor to liver-related morbidity and mortality among individuals with previous or current hepatitis B virus (HBV) exposure. Nutritional and inflammatory factors have been implicated in liver fibrosis, however their combined value for fibrosis stage classification remains insufficiently explored. This study aimed to investigate the associations of nutritional and inflammatory indicators with liver fibrosis severity and to develop machine-learning models for fibrosis stage classification. Methods This cross-sectional study analyzed data from the National Health and Nutrition Examination Survey (NHANES) 2017–2018 and 2019–2020 cycles. Individuals with evidence of previous or current HBV exposure (anti-HBc positive) were included. Liver fibrosis severity was assessed using transient elastography-derived liver stiffness measurements. Associations between clinical variables and fibrosis severity were evaluated using correlation analysis, univariate regression, and restricted cubic spline models. Random forest-based feature selection was performed, and six machine-learning algorithms, including Random Forest Support Vector Machine, Extreme Gradient Boosting (XGBoost), K-Nearest Neighbor, Decision Tree, and Neural Network, were developed and evaluated using repeated 10-fold cross-validation. Model performance was assessed using accuracy, multi area of under curve, F1-score, calibration analyses and . Results A total of 911 participants were included, comprising 769 individuals without fibrosis (84.41%), 39 with F1 fibrosis (4.28%), 52 with F2 fibrosis (5.71%), and 51 with F3 fibrosis (6.00%). Correlation and regression analyses demonstrated significant associations between liver fibrosis severity and multiple nutritional and inflammatory indicators. Restricted cubic spline analyses further revealed nonlinear relationships between fibrosis severity and age, BMI, GNRI, NPAR, and SIRI. Feature selection identified 10 key variables, including GNRI, BMI, albumin, total cholesterol, CRP, NPAR, creatinine, HDL cholesterol, waist-to-height ratio, and age. Among the six machine-learning algorithms evaluated, XGBoost achieved the best overall performance, with an accuracy of 0.940, a MAUC of 0.940, and a macro-F1 score of 0.804. Conclusions Nutritional and inflammatory indicators were significantly associated with liver fibrosis severity among individuals with previous or current HBV exposure. An XGBoost model constructed from routinely available clinical variables showed good performance in fibrosis stage classification and warrants further validation in independent cohorts.

Renal ischemia-reperfusion (I/R) injury is a major cause of acute kidney injury and transplant dysfunction, involving endoplasmic reticulum stress. Although activating transcription factor 6 (ATF6) regulates ER stress resolution through the unfolded protein response, its specific role in renal I/R injury remains undefined. Here, we employed murine models of renal I/R and cellular hypoxia/reoxygenation (H/R) models to systematically investigate ATF6's function. Our results show that I/R injury significantly upregulates ATF6 expression, particularly in proximal tubular epithelial cells. Functionally, ATF6 activation improved renal function and attenuated inflammation, whereas its inhibition exacerbated tubular damage. Mechanistically, we demonstrated that ATF6 transcriptionally represses four and a half LIM domain protein 2 (FHL2) through direct promoter binding. FHL2 in turn interacts with TRAF6 to activate the nuclear factor kappa-B (NF-κB) pathway. ATF6 overexpression effectively counteracted FHL2-mediated NF-κB hyperactivation, establishing a protective ATF6/FHL2/NF-κB axis. These findings identify ATF6 as a key renoprotective factor and reveal mechanistic avenues for potential therapies targeting renal I/R injury and transplant complications.

Background: The conversion therapy for advanced hepatocellular carcinoma (HCC) shows promise with a triple therapy approach that combines interventional therapy, immune checkpoint inhibitors, and molecular targeted therapy (primarily small-molecule TKIs and the large-molecule bevacizumab). This combination has achieved the highest objective response rates (ORR) along with acceptable safety profiles. The aim of this study was to compare the clinical efficacy of lenvatinib versus bevacizumab, when combined with immune checkpoint inhibitors and interventional triple therapy, as first-line treatments for Chinese patients with unresectable HCC (uHCC). Method: This retrospective multicenter study involved 371 consecutive patients from 21 centers in China, observed between April 2017 and December 2023. The study focused on patients with uHCC at Chinese liver cancer stages IIb to IIIb (Barcelona Clinic Liver Cancer stage B or C) who received lenvatinib or bevacizumab combined with anti-PD-1/L1 and interventional therapy (including TACE and/or HAIC) as first-line treatment. Of the 371 patients, 258 received lenvatinib-based triple therapy, while 113 received bevacizumab-based triple therapy. The primary endpoints were overall survival (OS) and progression-free survival (PFS). To balance baseline clinical characteristics, propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were applied. Subgroup analysis was also performed based on different clinicopathological characteristics of the enrolled uHCC patients. Results: The median OS in the lenvatinib group was significantly longer than in the bevacizumab group, both before (36.0 vs. 27.9 months; hazard ratio [HR]: 0.536; 95% confidence interval [CI]: 0.344–0.835; p = 0.0016) and after PSM (HR: 0.524; 95% CI: 0.305–0.900; p = 0.01), as well as after IPTW (HR: 0.549; 95% CI: 0.331–0.908; p = 0.01). Before adjustment, PFS in the lenvatinib group was also significantly longer than in the bevacizumab group (20.0 vs. 12.1 months; HR: 0.649; 95% CI: 0.457–0.922; p = 0.0078). However, after PSM (HR: 0.808; 95% CI: 0.535–1.222; p = 0.33) and IPTW, there was no significant difference in PFS between the two groups. Multivariate analysis showed that lenvatinib-based triple therapy was independently associated with improved OS compared to bevacizumab-based triple therapy. Subgroup analysis indicated that patients with age ≤65 years, no history of hepatitis B virus infection, Barcelona Clinic Liver Cancer stage C (BCLC-C), ALT levels ≤40 U/L, platelets ≥100 × 109/L, or log 10 AFP ≥1.40 benefited more from lenvatinib-based triple therapy. Conclusion: Lenvatinib-based triple therapy tends to prolong OS compared to bevacizumab, although the PFS was similar between the two groups. Patients aged ≤65 years, without a history of hepatitis B virus infection, with BCLC-C stage, ALT ≤40 U/L, platelets ≥100 × 109/L, or log 10 AFP ≥1.40 are likely to benefit more from lenvatinib-based triple therapy.

Hepatocellular carcinoma (HCC) is a biologically and clinically heterogeneous malignancy, whose initiation and progression are increasingly recognized to be driven by the aberrant regulation of programmed cell death (PCD) pathways. To elucidate this association, we systematically integrated gene signatures from 21 distinct PCD types to characterize their expression patterns in HCC and construct a prognostic model for survival and therapeutic response prediction. Based on the TCGA-LIHC, GSE14520, and GSE116174 datasets, 85 candidate genes were identified through differential expression analysis and random survival forest algorithms. A 10-gene PCD-based risk score model was developed using machine learning including key genes such as KIF20A (associated with ferroptosis) and SLC2A1 (associated with anoikis), which demonstrated robust prognostic performance across three independent cohorts by stratifying patients into high- and low-risk groups. The risk score significantly correlated with immune infiltration, immune evasion potential, and predicted sensitivity to multiple anticancer agents. Consensus clustering based on model gene expression revealed two molecular subtypes with distinct survival outcomes and immune characteristics. A nomogram integrating the risk score exhibited favorable calibration and clinical applicability. Collectively, these findings propose a novel PCD-based molecular framework for prognosis assessment and personalized therapy in HCC.

Accumulating evidence has demonstrated that biological processes associated with liquid-liquid phase separation (LLPS) play a critical role in cancer development. However, the effect of LLPS on hepatocellular carcinoma (HCC) remains largely unknown. In this study, we integrated consensus clustering with an ensemble machine learning framework to establish robust LLPS-related molecular subtypes and a consensus machine learning-driven LLPS-related signature (CMLLS) for HCC. The consensus clustering robustly identified three fundamental LLPS-driven subtypes (LS1-LS3), and the subsequent machine learning integration, which encompassed 101 algorithm combinations, objectively identified the most generalizable prognostic signature from multiple candidate genes. Our analysis revealed that LS3 exhibits the worst prognosis, significant upregulation of cell cycle and epithelial-mesenchymal transition (EMT)-related pathways, and enhanced immune resistance. Conversely, LS2 displays the best prognosis, enrichment in metabolism-related pathways, and increased sensitivity to immunotherapy. The CMLLS demonstrated robust predictive performance in prognostic stratification and effectively distinguished patients who would benefit from immunotherapy. This study provides novel insights into HCC heterogeneity at the LLPS level and offers a powerful tool for individualized treatment decision-making.

Hepatocellular carcinoma (HCC) is a malignant tumor with high incidence and mortality rates. NFKBIZ, a member of the nuclear factor kappa B inhibitory family, is closely related to tumor progression. However, the precise role of NFKBIZ in HCC remains unclear. To explore this, we conducted a series of experiments from clinic to cells. Western blot and qPCR revealed a significant downregulation of NFKBIZ in human HCC tissues. Clinical character analysis showed that the patients with lower NFKBIZ expression had poorer prognosis and higher clinical stage. By using CCK-8, wound healing, transwell invasion and migration assay, we discovered that NFKBIZ expression was reversely associated with the proliferation, invasion, and migration ability of HCC cells in vitro. Additionally, the results obtained from xenograft assay and lung metastasis models showed that NFKBIZ overexpression inhibited the growth and metastasis of HCC cells in vivo. Western blot and immunofluorescence assay further revealed that NFKBIZ mediated HCC cell growth and migration by regulating NFκB signaling transduction. Finally, flow cytometry, protein degradation assay and Co-immunoprecipitation indicated that TRIM16 can enhance NFKBIZ ubiquitination by direct interactions at its K48 site, which may thereby alleviate HCC cell apoptosis to induce the insensitivity to sorafenib. In conclusion, our study demonstrated that NFKBIZ regulated HCC tumorigenesis and metastasis by mediating NFκB signal transduction and TRIM16/NFKBIZ/NFκB axis may be the underlying mechanism of sorafenib insensitivity in HCC.

Background:Fostamatinib is the first spleen tyrosine kinase inhibitor approved for the treatment of chronic adult immune thrombocytopenia via blocking autoantibody-mediated platelet phagocytosis. Nevertheless, the potential of fostamatinib as therapeutic agent against acute inflammatory diseases has not been examined. This study aimed to investigate the effects of fostamatinib on the activation of macrophages and neutrophils and its therapeutic effects on SIRS. Methods:First, RT-qPCR and ELISA were used to detect the effects of fostamatinib on the expression and secretion of inflammatory factors by peritoneal macrophages (PMs) induced with TLR agonists. The activation and ROS release of neutrophils were detected by flow cytometry. Subsequently, the therapeutic effect of fostamatinib on LPS-induced SIRS in mice was examined. Finally, we also explored the underlying mechanisms of fostamatinib exerting pharmacodynamic effects by analyzing its effects on LPS-induced gene expression profile and the activation of signaling pathways in PMs through transcriptome sequencing and Western blot. Results:We found that fostamatinib inhibited the expression and secretion of TNF-α, IL-6, CCL2, CCL3, and CXCL10 (*P < 0.05) in PMs induced by LPS. Fostamatinib also reduced the activation of neutrophils stimulated by LPS, and suppressed the release of ROS by neutrophils. In SIRS mice, fostamatinib diminished the levels of inflammatory factors, and inhibited the excessive consumption of neutrophils in bone marrow. Transcriptome sequencing results showed that fostamatinib significantly inhibited the transcription of Cxcl10, Isg20, Mx1, Rsd2, etc. (*P < 0.05) in PMs induced by LPS. Meanwhile, fostamatinib selectively blocked the phosphorylation of STAT1 and STAT3 in PMs induced by LPS and cytokines (IFN-γ and IL-6). Conclusion:Fostamatinib can significantly inhibit LPS-induced inflammatory response through blocking STAT1/3 signaling pathways and has the potential to be used in the therapy of acute inflammatory diseases, especially SIRS and sepsis, which are resulting from the infection of Gram-negative bacteria.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, with the characteristics of high mortality and low 5-year survival rate. The potential role of BTF3 and PDCD2L in HCC remains unclear. Our study found that BTF3 expression was upregulated in hepatocellular carcinoma tissues, and its high expression was associated with poor prognosis. Knockdown of BTF3 significantly inhibited proliferation and promoted apoptosis of hepatocellular carcinoma cells by cell function assay. Mechanistically, BTF3 plays an oncogenic role by regulating the transcriptional expression of PDCD2L, which promotes proliferation and inhibits apoptosis of HCC cells by restraining the p53 pathway. In conclusion, our results suggest that BTF3 induces malignant progression of HCC by acting as a transcription factor that promotes the transcription of PDCD2L and influences the p53 pathway and that the BTF3/PDCD2L/P53 axis may be a future therapeutic strategy for HCC patients.

BACKGROUND The difference in the prognoses between treatment with surgical therapy and continuation of local-plus-systemic therapy following successful down-staging of intermediate-advanced hepatocellular carcinoma (HCC) remains unclear. METHODS Data of 405 patients with intermediate-advanced HCC treated at 30 hospitals across China from January 2017 to July 2022 were retrospectively reviewed. All patients received local-plus-systemic therapy and were divided into the surgical (n = 100) and nonsurgical groups (n = 305) according to whether they received surgical therapy. The differences between long-term prognoses of the 2 groups were compared. Subgroup analysis was performed in 173 HCC patients who met the criteria for surgical resection following down-staging. RESULTS Multivariable analysis of all patients showed that surgical therapy, hazard ratio (HR): 0.289, 95% confidence interval, CI, 0.136-0.613) was a protective factor for overall survival (OS), but not for event-free survival (EFS). Multivariable analysis of 173 intermediate-advanced HCC patients who met the criteria for surgical resection after conversion therapy showed that surgical therapy (HR: 0.282, 95% CI, 0.121-0.655) was a protective factor for OS, but not for EFS. Similar results were obtained after propensity score matching. For patients with Barcelona Clinic Liver Cancer stage B (HR: 0.171, 95% CI, 0.039-0.751) and C (HR: 0.269, 95% CI, 0.085-0.854), surgical therapy was also a protective factor for OS. CONCLUSIONS Overall, for patients with intermediate-advanced HCC who underwent local-plus-systemic therapies, surgical therapy is a protective factor for long-term prognosis and can prolong OS, and for those who met the surgical resection criteria after conversion therapy, surgical therapy is recommended.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths. However, the HCC treatment is still challenging. Herein, we aimed to reveal the anti-tumor effect of Jolkinolide B in HCC cell lines Huh-7 and SK-Hep-1. The results showed that Jolkinolide B inhibited the migration, invasion, and epithelial-to-mesenchymal transition(EMT) of HCC cells. In addition, Jolkinolide B induced HCC cell apoptosis by upregulating Bax and downregulating BCL-2 expressions. Furthermore, we demonstrated that Jolkinolide B inactivated the β-catenin signaling and reduced Musashi-2 expression. Finally, we revealed that Musashi-2 overexpression reversed the Jolkinolide B-induced anti-HCC effect. Overall, we proved that Jolkinolide B is a potential candidate for treating HCC.

Hepatocellular carcinoma (HCC) is the most common malignancy in the liver, with a poor prognosis. Transmembrane protein 209 (TMEM209) involves multiple biological processes, such as substance transportation and signal transduction, and is abundantly expressed in tumor tissues. However, the relationship between TMEM209 and HCC has not been comprehensively elucidated. In this study, we aimed to illustrate this issue by in vitro and in vivo experiments. Bioinformatic analysis and clinical sample validation revealed that TMEM209 was upregulated in HCC and correlated with reduced survival duration. Functionally, TMEM209 promoted the proliferation, migration, invasion, and EMT of HCC cells in vitro and facilitated tumor growth and metastasis in xenograft models. Mechanistically, TMEM209 promoted the proliferation and metastasis of HCC in a KPNB1-dependent manner. Specifically, TMEM209 could bind to KPNB1, thereby competitively blocking the interaction between KPNB1 and the E3 ubiquitin ligase RING finger and CHY zinc finger domain-containing protein 1 (RCHY1) and preventing K48-associated ubiquitination degradation of KPNB1. Ultimately, the Wnt/β-catenin signaling pathway was activated, contributing to the progression of the malignant phenotype of HCC. In conclusion, the molecular mechanism underlying the TMEM209/KPNB1/Wnt/β-catenin axis in HCC progression was elucidated. TMEM209 is a potential biomarker and therapeutic target for HCC.

Although the death of hepatocytes is a crucial trigger of liver ischemia-reperfusion (I/R) injury, the regulation of liver I/R-induced hepatocyte death is still poorly understood. Phosphoglycerate mutase 5 (PGAM5), a mitochondrial Serine/Threonine protein phosphatase, regulates mitochondrial dynamics and is involved in the process of both apoptosis and necrotic. However, it is still unclear what role PGAM5 plays in the death of hepatocytes induced by I/R. Using a PGAM5-silence mice model, we investigated the role of PGAM5 in liver I/R injury and its relevant molecular mechanisms. Our data showed that PGAM5 was highly expressed in mice with liver I/R injury. Silence of PGAM5 could decrease I/R-induced hepatocyte death in mice. In subcellular levels, the silence of PGAM5 could restore mitochondrial membrane potential, increase mitochondrial DNA copy number and transcription levels, inhibit ROS generation, and prevent I/R-induced opening of abnormal mPTP. As for the molecular mechanisms, we indicated that the silence of PGAM5 could inhibit Drp1(S616) phosphorylation, leading to a partial reduction of mitochondrial fission. In addition, Mdivi-1 could inhibit mitochondrial fission, decrease hepatocyte death, and attenuate liver I/R injury in mice. In conclusion, our data reveal the molecular mechanism of PGAM5 in driving hepatocyte death through activating mitochondrial fission in liver I/R injury.

Phosphoglycerate mutase/protein phosphatase (PGAM5)-mediated cell death plays an important role in multiple liver diseases. However, few studies have confirmed the regulatory mechanism of melatonin acting on PGAM5-mediated cell death in the context of liver ischemia-reperfusion (I/R) injury. The liver I/R injury model and cell hypoxia-reoxygenation model were established after melatonin pretreatment. Liver injury, cell activity, cell apoptosis, oxidative stress index, and PGAM5 protein expression were detected. To investigate the role of PGAM5 in melatonin-mediated liver protection during I/R injury, PGAM5 silencing, and overexpression were performed before melatonin pretreatment. Our results indicated that PGAM5 was significantly elevated by I/R injury, and predominantly localized in the necrosis area. However, treatment with melatonin blocked PGAM5 activation and conferred a survival advantage of hepatocytes in liver I/R injury, similar to the results achieved by silencing PGAM5. In terms of mechanism, we illustrated that activated PGAM5 promoted mitochondrial permeability transition pore (mPTP) opening, and administration of melatonin inhibited mPTP opening and interrupted hepatocytes death via blocking PGAM5. Our data indicated that the PGAM5-mPTP axis is responsible for I/R-induced liver injury. In contrast, melatonin supplementation blocked the PGAM5-mPTP axis and thus decreased cell death, providing a protective advantage to hepatocytes in I/R. These results established a new paradigm in melatonin-mediated hepatocyte protection under the burden of I/R attack.

Betaine-homocysteine methyltransferase (BHMT) regulates protein methylation and is correlated with tumorigenesis; however, the effects and regulation of BHMT in hepatocarcinogenesis remain largely unexplored. Here, we determined the clinical significance of BHMT in the occurrence and progression of hepatocellular carcinoma (HCC) using tissue samples from 198 patients. BHMT was to be frequently found (86.6%) expressed at relatively low levels in HCC tissues and was positively correlated with the overall survival of patients with HCC. Bhmt overexpression effectively suppressed several malignant phenotypes in hepatoma cells in vitro and in vivo, whereas complete knockout of Bhmt (Bhmt-/-) produced the opposite effect. We combined proteomics, metabolomics, and molecular biological strategies and detected that Bhmt-/- promoted hepatocarcinogenesis and tumor progression by enhancing the activity of glucose-6-phosphate dehydrogenase (G6PD) and PPP metabolism in DEN-induced HCC mouse and subcutaneous tumor-bearing models. In contrast, restoration of Bhmt with an AAV8-Bhmt injection or pharmacological inhibition of G6PD attenuated hepatocarcinogenesis. Additionally, coimmunoprecipitation identified monomethylated modifications of the G6PD, and BHMT regulated the methylation of G6PD. Protein sequence analysis, generation and application of specific antibodies, and site-directed mutagenesis indicated G6PD methylation at the arginine residue 246. Furthermore, we established bidirectionally regulated BHMT cellular models combined with methylation-deficient G6PD mutants to demonstrate that BHMT potentiated arginine methylation of G6PD, thereby inhibiting G6PD activity, which in turn suppressed hepatocarcinogenesis. Taken together, this study reveals a new methylation-regulatory mechanism in hepatocarcinogenesis owing to BHMT deficiency, suggesting a potential therapeutic strategy for HCC treatment.

In this work, a series of novel arylamide derivatives containing piperazine moiety were designed and synthesised as tubulin polymerisation inhibitors. Among 25 target compounds, compound 16f (MY-1121) exhibited low nanomolar IC50 values ranging from 0.089 to 0.238 & mu;M against nine human cancer cells. Its inhibitory effects on liver cancer cells were particularly evident with IC50 values of 89.42 and 91.62 nM for SMMC-7721 and HuH-7 cells, respectively. Further mechanism studies demonstrated that compound 16f (MY-1121) could bind to the colchicine binding site of & beta;-tubulin and directly act on & beta;-tubulin, thus inhibiting tubulin polymerisation. Additionally, compound 16f (MY-1121) could inhibit colony forming ability, cause morphological changes, block cell cycle arrest at the G2 phase, induce cell apoptosis, and regulate the expression of cell cycle and cell apoptosis related proteins in liver cancer cells. Overall, the promising bioactivities of compound 16f (MY-1121) make the novel arylamide derivatives have the value for further development as tubulin polymerisation inhibitors with potent anticancer activities.

Arachidonic acid metabolism plays a crucial role in the development and progression of inflammatory and metabolic liver diseases. However, its role in hepatocellular carcinoma (HCC) remains unclear. In this study, we investigated the expression of key genes involved in the arachidonic acid metabolism pathway in HCC using a combination of bioinformatics, proteomics and immunohistochemistry analyses. Through a comprehensive analysis of publicly available datasets, clinical HCC tissues, and tissue microarrays, we compared the expression of hepatic arachidonic acid metabolic genes. We observed significant downregulation of cytochrome P450 (CYP450) pathway genes at both the messenger RNA and protein levels in HCC tissues compared to normal liver tissues. Furthermore, we observed a strong correlation between the deregulation of the arachidonic acid metabolism CYP450 pathway and the pathological features and prognosis of HCC. Specifically, the expression of CYP2C8/9/18/19 was significantly correlated with pathological grade (r = -.484, p < .0001), vascular invasion (r = -.402, p < .0001), aspartate transaminase (r = -.246, p = .025), gamma-glutamyl transpeptidase (r = -.252, p = .022), alkaline phosphatase (r = -.342, p = .002), alpha-fetoprotein (r = -.311, p = .004) and carbohydrate antigen 19-9 (r = -.227, p = .047). Moreover, we discovered a significant association between CYP450 pathway activity and vascular invasion in HCC. Collectively, these data indicate that arachidonic acid CYP450 metabolic pathway deregulation is implicated in HCC progression and may be a potential predictive factor for early recurrence in patients with HCC.

Background: Autism spectrum disorder (ASD) includes a range of multifactorial neurodevelopmental disabilities characterized by a variable set of neuropsychiatric symptoms. Immunological abnormalities have been considered to play important roles in the pathogenesis of ASD, but it is still unknown which abnormalities are more prominent. Methods: A total of 105 children with ASD and 105 age and gender-matched typically developing (TD) children were recruited. An eating and mealtime behavior questionnaire, dietary habits, and the Bristol Stool Scale were investigated. The immune cell profiles in peripheral blood were analyzed by flow cytometry, and cytokines (IFN-gamma, IL-8, IL-10, IL-17A, and TNF-alpha) in plasma were examined by Luminex assay. The obtained results were further validated using an external validation cohort including 82 children with ASD and 51 TD children. Results: Compared to TD children, children with ASD had significant eating and mealtime behavioral changes and gastrointestinal symptoms characterized by increased food fussiness and emotional eating, decreased fruit and vegetable consumption, and increased stool astriction. The proportion of gamma delta T cells was significantly higher in children with ASD than TD children (beta: 0.156; 95% CI: 0.888 similar to 2.135, p < 0.001) even after adjusting for gender, eating and mealtime behaviors, and dietary habits. In addition, the increased gamma delta T cells were evident in all age groups (age < 48 months: beta: 0.288; 95% CI: 0.420 similar to 4.899, p = 0.020; age > 48 months: beta: 0.458; 95% CI: 0.694 similar to 9.352, p = 0.024), as well as in boys (beta: 0.174; 95% CI: 0.834 similar to 2.625, p < 0.001) but not in girls. These findings were also confirmed by an external validation cohort. Furthermore, IL-17, but not IFN-gamma, secretion by the circulating gamma delta T cells was increased in ASD children. Machine learning revealed that the area under the curve in nomogram plots for increased gamma delta T cells combined with eating behavior/dietary factors was 0.905, which held true in both boys and girls and in all the age groups of ASD children. The decision curves showed that children can receive significantly higher diagnostic benefit within the threshold probability range from 0 to 1.0 in the nomogram model. Conclusions: Children with ASD present with divergent eating and mealtime behaviors and dietary habits as well as gastrointestinal symptoms. In peripheral blood, gamma delta T cells but not alpha beta T cells are associated with ASD. The increased gamma delta T cells combined with eating and mealtime behavior/dietary factors have a high value for assisting in the diagnosis of ASD.

Emerging evidence suggests that epigenetic alterations are responsible for the oncogenesis and progression of cancer. However, the role of epigenetic reprogramming in pancreatic cancer is still not clear. In this study, we used the limma R package to identify differentially expressed protein-coding genes (PCGs) between pancreatic cancer tissues and normal control tissues. The cell-type identification by the estimating relative subsets of RNA transcripts (CIBERSORT) package was used to quantify relative cell fractions in tumors. Prognostic molecular clusters were constructed using ConsensusClusterPlus analysis. Furthermore, the least absolute shrinkage and selection operator and stepAIC methods were used to construct a risk model. We identified 2351 differentially expressed PCGs between pancreatic cancer and normal control tissues in The cancer genome atlas dataset. Combined with histone modification data, we identified 363 epigenetic PCGs (epi-PCGs) and 19,010 non-epi-PCGs. Based on the epi-PCGs, we constructed three molecular clusters characterized by different expression levels of chemokines and immune checkpoint genes and distinct abundances of various immune cells. Furthermore, we generated a 9-gene model based on dysfunctional epi-PCGs. Additionally, we found that patients with high risk scores showed poorer prognoses than patients with low risk scores ( p < 0.0001). Further analysis showed that the risk score was significantly related to survival and was an independent risk factor for pancreatic cancer patients. In conclusion, we constructed a 9-gene prognostic risk model based on epi-PCGs that might serve as an effective classifier to predict overall survival and the response to immunotherapy in pancreatic cancer patients.

9p缺失综合征又称为Alfi's综合征(OMIM158170),是一种多器官受累的少见的遗传性疾病,主要临床特点为发育迟缓、智力障碍、特殊面容、多器官畸形,部分患者可有孤独症样表现及性发育异常[1].性反转综合征是一类性别发育异常的遗传学疾病,主要特征是染色体性别和性腺性别不相符,包括46,XX男性和46,XY女性[2].孤独症谱系障碍(autism spectrum disorder,ASD)作为一种神经发育障碍性疾病,以社交沟通障碍、刻板行为和/或兴趣狭窄为主要临床表现,病因尚不明确.9p缺失综合征合并性发育异常及ASD报道较多,但同时合并三种疾病的病例极为罕见.本文对郑州大学第三附属医院儿童发育行为科收治的1例9p缺失综合征儿童同时合并46,XY性反转及ASD报道如下.

Objective To study the therapeutic effect of avatrombopag on severe thrombocytopenia（TCP） in patients waiting for liver transplantation. Methods This study was conducted by analyzing the clinical data of 67 patients waiting for liver transplantation with severe TCP in the First Affiliated Hospital of Zhengzhou University from February 2021 to October 2022. The general information of patients and their platelet count before and after avatrombopag treatment were collected in this study. Patients were divided into two groups for further analysis according to whether recombinant human thrombopoietin（rhTPO） was used at same time. Platelet count no less than 50×10~9/L after treatment of avatrombopag was considered as effective response. Results The platelet count of 67 patients waiting for liver transplantation with severe TCP was significantly elevated after using avatrombopag（P = 0.001）. Moreover, the platelet counts of 89.55%（60/67） patients were higher than 50×10~9/L and there was no significant difference in the effective rate between different thrombocytopenia groups（P = 0.373）. Further analysis showed that combined therapy group（avatrombopag and rhTPO） acquired significant higher platelet count than monotherapy group（P = 0.002） with similar basal count level before treatment（P = 0.064）. Furthermore, the percentage of patients whose platelet counts were more than 50×10~9/L had no significant difference（P = 0.228） between avatrombopag group 85.00%（34/40） and combined group 96.30%（26/27）. Conclusion Avatrombopag could increase the platelet level in severe TCP patients waiting for liver transplantation. Avatrombopag combined with rhTPO may have better therapeutic effect.