Icodextrin peritoneal dialysis solution may produce cytotoxic α-dicarbonyl degradation products during heat sterilization, which must be monitored and controlled. The study established an o-phenylenediamine (OPD) derivatization HPLC-MS/MS method for the detection of these degradation products, enabling qualitative and quantitative analysis of α-dicarbonyl degradation products in icodextrin peritoneal dialysis solution. The results indicated that the main α-dicarbonyl degradation products in icodextrin peritoneal dialysis solution are 3-deoxyglucosone (3-DG), 3-deoxygalactosone (3-DGal), 4-deoxyglucosone (4-DG), and 3,4-dideoxyglucosone-3-ene (3,4-DGE), along with two monocarbonyl degradation products, furfural and 5-hydroxymethylfurfural. The quantitative method for 3-DG, 3-DGal, 3,4-DGE and their structural analog, glucosone, was validated. 3-DG, 3-DGal, and glucosone exhibited good linear relationships within the range of 5-150 ng/mL, while 3,4-DGE showed good linearity in the range of 1-150 ng/mL. The spiked recovery rates for all compounds were between 86.8% and 100.0%. The detection limits for glucosone, 3-DG, and 3-DGal were approximately 2.4 ng/mL, and approximately 0.5 ng/mL for 3,4-DGE. The method established in this study can accurately determine α-dicarbonyl degradation products in icodextrin peritoneal dialysis solution, providing an important basis for the quality control.

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

OBJECTIVES: To explore the mechanism of Lacticaseibacillus paracasei E6 for improving vinorelbine-induced immunosuppression in zebrafish. METHODS: The intestinal colonization of L. paracasei E6 labeled by fluorescein isothiocyanate (FITC) in zebrafish was observed under fluorescence microscope. In a zebrafish model of vinorelbine-induced immunosuppression, the immunomodulatory activity of L. paracasei E6 was assessed by analyzing macrophage and neutrophil counts in the caudal hematopoietic tissue (CHT), the number of T-lymphocyte, and the expressions of interleukin-12 (IL-12) and interferon-γ (IFN-γ). The contents of short-chain fatty acids (SCFAs) in L. paracasei E6 fermentation supernatant and the metabolites of L. paracasei E6 in zebrafish were detected by LC-MS/MS-based targeted metabolomics. The immunomodulatory effects of the SCFAs including sodium acetate, sodium propionate and sodium butyrate were evaluated in the zebrafish model of immunosuppression. RESULTS: After inoculation, green fluorescence of FITC-labeled L. paracasei E6 was clearly observed in the intestinal ball, midgut and posterior gut regions of zebrafish. In the immunocompromised zebrafish model, L. paracasei E6 significantly alleviated the reduction of macrophage and neutrophil counts in the CHT, increased the fluorescence intensity of T-lymphocytes, and promoted the expressions of IL-12 and IFN-γ. Compared with MRS medium, L. paracasei E6 fermentation supernatant showed significantly higher levels of acetic acid, propionic acid and butyric acid, which were also detected in immunocompromised zebrafish following treatment with L. paracasei E6. Treatment of the zebrafish model with sodium acetate and sodium propionate significantly increased macrophage and neutrophil counts in the CHT and effectively inhibited vinorelbine-induced reduction of thymus T cells. CONCLUSIONS L. paracasei E6 can improve vinorelbine-induced immunosuppression in zebrafish through its SCFA metabolites acetic acid and propionic acid.
Animals ; Zebrafish/immunology* ; Acetic Acid/metabolism* ; Propionates/metabolism* ; Fatty Acids, Volatile/metabolism*

Chinese medicine therapy for removing gallstones is one of the methods for the treatment of cholelithiasis.In the view of Professor Liu Fengbin,attacking of external pathogens,improper diet and emotional disorders contribute to the main causes of cholelithiasis,and the pathogenesis of cholelithiasis is due to qi stagnation of both liver and gallbladder,and internal obstruction of damp-heat.The occurrence of cholelithiasis is closely related to deficiency of spleen and stomach,and is correlated with the pathological factors of turbid phlegm and blood stasis.For the Chinese medicine treatment of cholelithiasis,Professor Liu follows the principle of"treatment in accordance with three categories of etiological factors"(i.e,seasons,environment and body constitution).He advocates the integration of traditional Chinese medicine and western medicine,and is good at utilizing Lingnan herbs and distinctive herbs that can dissolve stones and remove stones.The treatment for cholelithiasis is mainly through the therapies of soothing liver and alleviating depression,clearing heat and removing dampness,and normalizing gallbladder function to remove stones,and is also supplemented by the therapies of invigorating spleen and replenishing qi,regulating qi to resolve phlegm,and activiting qi movement and blood circulation.Modified Da Chaihu Decoction plus Sijin Decoction is often used as a basic formula for treating cholelithiasis,which is mainly composed of Desmodii Styracifolii Herba,Galli Gigerii Endothelium Corneum,Bupleuri Radix,Curcumae Radix,Scutellariae Radix,Aucklandiae Radix,Aurantii Fructus Immaturus stir-fried with bran,Paeoniae Radix Rubra,Linderae Radix,and Rhei Radix et Rhizoma.

Professor Liu Fengbin,a renowned traditional Chinese medicine(TCM)expert in Guangdong Province,specializes in treating digestive system disorders of hepatobiliary and splenic diseases with Chinese herbal medicine,and has accumulated extensive experience in intervening viral hepatitis type B and hepatitis B-related liver fibrosis.Professor Liu proposes that dampness,heat,stasis,toxin,and deficiency are the primary pathogenic factors of hepatitis B-related liver fibrosis.The disease is rooted in the liver,and is also closely related to the spleen and kidney and involves the gallbladder,stomach,and triple energizer.Based on TCM dialectical thinking and years of clinical practice,Professor Liu summarized the"eight methods for treating liver diseases"for intervening hepatitis B-related liver fibrosis with Chinese medicine,i.e.,method of activating the spleen and stomach,method of clearing heat and dispelling dampness,method of dispelling dampness and resolving turbidity,method of enriching yin and subduing fire,method of warming yang and tonifying the kidney,method of softening the liver and nourishing blood,method of activating blood circulation and softening hardness,and method of calming the mind and improving sleep.In clinical practice,these methods are flexibly combined based on patients'syndrome types and manifestations.Moreover,Professor Liu is skilled in using herbal groups having Lingnan medicinal characteristics,such as herbal group for clearing heat and removing toxin,and draining dampness to relieve jaundice which is composed of Mallotus Apelta Radix et Rhizoma,Abri Herba and Phyllanthi Urinariae Herba,herbal group for promoting digestion to remove food retention which is composed of Fermentum Rubrum,Crataegi Fructus and Hordei Fructus Germinatus,herbal group for removing blood and eliminating mass group which is composed of vinegar-processed Curcumae Rhizoma,vinegar-processed Trionycis Carapax and Eupolyphaga Steleophaga,and herbal group for protecting liver and lowering enzyme which is composed of Hoveniae Semen and Schisandrae Chinensis Fructus.Professor Liu's medication experience for intervening hepatitis B-related liver fibrosis will provide valuable references for TCM clinical practice in the management of liver diseases.

Animal experiments are an essential component of life sciences and medical research. However, the external validity and reliability of individual animal studies are frequently challenged by inherent limitations such as small sample sizes, high design heterogeneity, and poor reproducibility, which impede the effective translation of research findings into clinical practice. Systematic reviews and meta-analysis represent a key methodology for integrating existing evidence and enhancing the robustness of conclusions. Currently, however, the application of systematic reviews and meta-analysis in the field of animal experiments lacks standardized guidelines for their conduct and reporting, resulting in inconsistent quality and, to some extent, diminishing their evidence value. To address this issue, this paper aims to systematically delineate the reporting process for systematic reviews and meta-analysis of animal experiments and to propose a set of standardized recommendations that are both scientific and practical. The article's scope encompasses the entire process, from the preliminary preparatory phase [including formulating the population， intervention， comparison and outcome （PICO） question, assessing feasibility, and protocol pre-registration] to the key writing points for each section of the main report. In the core methods section, the paper elaborates on how to implement literature searches, establish eligibility criteria, perform data extraction, and assess the risk of bias, based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis （PRISMA) statement, in conjunction with relevant guidelines and tools such as Animal Research： Reporting of in Vivo Experiments （ARRIVE) and a risk of bias assessment tool developed by the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE). For the presentation of results, strategies are proposed for clear and transparent display using flow diagrams and tables of characteristics. The discussion section places particular emphasis on how to scientifically interpret pooled effects, thoroughly analyze sources of heterogeneity, evaluate the impact of publication bias, and cautiously discuss the validity and limitations of extrapolating findings from animal studies to clinical settings. Furthermore, this paper recommends adopting the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to comprehensively grade the quality of evidence. Through a modular analysis of the entire reporting process, this paper aims to provide researchers in the field with a clear and practical guide, thereby promoting the standardized development of systematic reviews and meta-analysis of animal experiments and enhancing their application value in scientific decision-making and translational medicine.

Objective:To explore the clinical and genetic characteristics of X-linked intellectual disability associated with HUWE1 gene variants.Methods:A cases series study retrospectively analyzed the clinical data of 6 children with HUWE1 gene variants. The children were identified from the Third Affiliated Hospital of Zhengzhou University, the First Affiliated Hospital of Zhengzhou University, the First Affiliated Hospital of Henan University of Chinese Medicine, and Guangzhou Women and Children′s Medical Center of Guangzhou Medical University between April 2021 and July 2023.The data included sex, age, dysmorphic features, intellectual and motor development, seizure history, neuroimaging findings, family history, and genetic results was analyzed.Results:A total of 6 children, including 5 boys and 1 girl. The age of onset ranged from 1 day to 3 years. All children presented with varying degrees of intellectual disability, with or without motor developmental delay. Dysmorphic features were observed in 4 children, including microcephaly in 3 children. Short stature were observed in 3 children. One child was diagnosed with autism spectrum disorders and 1 child had seizures. Two boys had relevant maternal family histories of febrile seizures and mild intellectual disability, respectively. Abnormal neuroimaging findings were presented in 4 children, including cerebral dysplasia (1 child), prominent supratentorial ventricles (1 child), and mild white matter demyelination (2 children). Whole-exome sequencing identified 5 missense variants and 1 in-frame deletion variant. Five variants were novel and previously unreported (c.12290C>T, c.12701T>C, c.9875C>T, c.9641A>T and c.10313_10315del). The variants in 4 boys were maternally inherited, while the remaining 2 children had de novo variants. The child with the in-frame deletion variant (c.10313_10315del) presented with the most severe phenotype, exhibiting symptoms from 1 day of age, absent cognitive development, feeding difficulties, and congenital laryngeal chondrodysplasia. He was lost to follow-up at 3 months of age after treatment was withdrawn. The age at the last follow-up for the remaining 5 children ranged from 2 years and 10 months to 17 years. A boy with seizures died at 2 years and 10 months of age. The remaining 4 children were able to walk independently at the last follow-up, although their developmental progress was slow. Conclusions:HUWE1 gene related X-linked intellectual disability is characterized by varying degrees of developmental delay and intellectual disability, frequently accompanied by microcephaly, short stature, and occasionally by seizures and autism spectrum disorders. Missense variants are more common and the in-frame deletion variant appears to be associated with a particularly severe phenotypic presentation.

Bone metastasis,as a common terminal event in patients with advanced malignant tumors,significantly impacts patients'quality of life and survival prognosis,posing a major clinical challenge in the field of oncology.With the deepening understanding of tumor biology,the treatment paradigm for bone metastasis has progressively shifted from traditional palliative care to precise targeted interventions.Currently,clinical treatment strategies have demonstrated diversified development,with various therapeutic approaches-including radiotherapy,immunotherapy,bone-modifying agents,and small-molecule targeted drugs—achieving notable clinical progress.However,existing treatment regimens still face challenges such as significant interindividual variability in efficacy,frequent drug resistance,and prominent adverse effects.This article systematically reviews the latest advances in precision therapy for bone metastasis,provides an in-depth analysis of the strengths and limitations of different treatment strategies,and offers perspectives on future research directions and therapeutic prospects,aiming to provide reference for optimizing clinical practice and promoting translational research.

This paper summarizes Professor LIU Fengbin's clinical experience in treating autoimmune liver disease （AILD） using the method of nourishing yin and removing stasis based on stage differentiation. He believes that the pathogenesis of AILD generally involves both deficiency in essence and excess in manifestation， with essence deficiency often presenting as liver and kidney yin deficiency， which may progress to spleen deficiency and yang deficiency over time. The excess manifestation commonly includes qi stagnation， blood stasis， damp-heat， and phlegm toxicity. Clinically， he advocates for the treatment principle of nourishing yin and removing stasis. On the foundation of nourishing liver and kidney yin， different pathological factors causing stasis are eliminated according to their nature. Treatment is also tailored to different stages of AILD. In the early and asymptomatic stages， liver qi stagnation and spleen deficiency are prominent， warranting a therapeutic approach of soothing the liver， regulating qi and strengthening the spleen. The modified Chaishao Qizhi Decoction （柴芍气滞汤） is used. During the symptomatic stage， pathogenic factors become more pronounced， often accompanied by a significant deficiency of vital qi， with damp-heat， water retention， and phlegm toxicity as key pathological features. The treatment should focus on strengthening the spleen and dispelling dampness， using modified Sijunzi Decoction （四君子汤） combined with Yinchen Wuling Powder （茵陈五苓散）. In the liver function decompensation stage， vital qi is severely deficient while pathogenic factors persist， with damp-heat， phlegm toxicity， and blood stasis obstructing the liver collaterals. Treatment should focus on nourishing blood， softening the liver， strengthening the spleen， and resolving stasis， using the modified Ruangan Yangxue Decoction （软肝养血汤）. Throughout the treatment process， emphasis is placed on tonifying the liver and kidneys while protecting yin fluids.