ObjectiveTo observe the clinical efficacy of Sanren Runchang formula in treating constipation-predominant irritable bowel syndrome （IBS-C） by regulating the brain-gut axis and the effects of the formula on serum levels of 5-hydroxytryptamine （5-HT）， vasoactive intestinal peptide （VIP）， and substance P （SP）. MethodsA randomized controlled design was adopted， and 72 IBS-C patients meeting Rome Ⅳ criteria were randomized into observation and control groups （36 cases）.The observation group received Sanren Runchang formula granules twice daily， and the control group received lactulose oral solution daily for 4 weeks. IBS Symptom Severity Scale （IBS-SSS）， IBS Quality of Life Scale （IBS-QOL）， and Bristol Stool Form Scale （BSFS） were used to assess clinical symptoms， and bowel movement frequency was recorded. The Self-Rating Anxiety Scale （SAS） and Self-Rating Depression Scale （SDS） were employed to evaluate psychological status. ELISA was employed to measure the serum levels of 5-HT， VIP， and SP. ResultsThe total response rate in the observation group was 91.67% （33/36）， which was higher than that （77.78%， 28/36） in the control group （χ²=4.50， P<0.05）. After treatment， both groups showed increased defecation frequency and BSFS scores， decreased IBS-SSS total score， abdominal pain and bloating scores， IBS-QOL health anxiety， anxiety， food avoidance， and behavioral disorders scores， SAS and SDS scores， serum 5-HT and VIP levels， and increased SP levels （P<0.05， P<0.01）. Moreover， the observation group showed more significant changes in the indicators above than the control group （P<0.05， P<0.01）. The SP level showed no significant difference between the two groups. During the 4-week follow-up， the recurrence rate was 5.88% in the observation group and 31.25% in the control group. No adverse events occurred in observation group， and 2 cases of mild diarrhea occurred in the control group. ConclusionSanren Runchang formula demonstrated definitive efficacy in alleviating gastrointestinal symptoms and improving the psychological status and quality of life in IBS-C patients， with a low recurrence rate. The formula can regulate serum levels of neurotransmitters such as 5-HT and VIP， suggesting its potential regulatory effect on the brain-gut axis through modulating neurotransmitters and neuropeptides. However， its complete mechanism of action requires further investigation through detection of additional brain-gut axis-related biomarkers.

ObjectiveThe most prevalent mRNA modification, N6-methyladenosine (m⁶A) plays an important role in various RNA metabolism, including gene expression and translation. By recruiting different “reader” proteins and their cofactors, m⁶A modification can affect messenger RNA (mRNA) degradation, splicing, nuclear export and translation. However, the selective mechanism by which m⁶A sites regulate mRNA translation through m⁶A reader YTHDF1 binding remains poorly understood, due to a lack of computational methods for identifying context-specific m⁶A sites that regulate translation. To address this, we developed a novel computational framework named m⁶ATEpre, the first tool designed to predict cell-specific m⁶A sites that regulate translation efficiency. Methodsm⁶ATEpre integrates multi-omics data, introduces a novel feature representation strategy for m⁶A site sequences, and employs an autoencoder to effectively capture embedded feature representations. Specifically, m⁶ATEpre first integrated MeRIP-seq data and PAR-CLIP data through overlapping m⁶A sites with YTHDF1 binding sites and identified YTHDF1-mediated m⁶A sites. Then, m⁶ATEpre detected the translation gene by analyzing the Ribo-seq data under YTHDF1 knockdown vs control condition. Genes whose translation is mediated by YTHDF1 in an m⁶A-dependent manner were identified by a significant decrease in translation efficiency upon YTHDF1 knockdown. Next, we proposed a binary vector indicating the presence or absence of YTHDF1 binding motifs to characterize each m⁶A site sequence. This represents a novel feature representation strategy for m⁶A sites. m⁶ATEpre utilized the autoencoder to extract the potentially important feature representations and constructed a multilayer perceptron neural networks model to predict potential m⁶A sites that regulating translation efficiency. ResultsA comprehensive evaluation of m⁶ATEpre was conducted through a series of experiments. We compared its performance against that of a similar prediction task model, as well as other classifiers. The results indicate that m⁶ATEpre achieved the best prediction performance. In addition, we analyzed different feature representation strategies and performed ablation experiments to validate the rationality of the model design. The results demonstrate that our proposed feature representation strategy has a greater advantage in improving prediction performance. In the HeLa cell line, bioinformatic analysis of the metagene distribution and sequence minimum free energy of m⁶A sites regulating translation efficiency (m⁶A-reg-TE sites) revealed their specific properties in translation regulation. Functional enrichment analysis indicated that m⁶A-reg-TE genes are associated with specific biological processes and KEGG pathways. By integrating the binding sites of YTHDF1 co-factors with m⁶A-reg-TE sites, we revealed that YTHDF1-mediated and m⁶A-dependent translation efficiency regulation requires the cooperation of multiple translation-regulatory RNA-binding proteins among its co-factors in the HeLa cell line. Furthermore, we extended our predictions to the dataset of the HEK293T cell line. Similarly, bioinformatic analysis of the metagene distribution and functional enrichment revealed the cell-specific characteristic of these predicted m⁶A-reg-TE sites in HEK293T cells. Likewise, integrated analysis of multiple YTHDF1 co-factors and m⁶A-reg-TE sites predicted in the HEK293T cell line reveals their m⁶A-dependent cooperation in regulating translation efficiency. Conclusionm⁶ATEpre is a timely tool that will advance our understanding of the mechanisms of m⁶A regulation in translation efficiency. The source code and datasets used in this work can be downloaded from https://www.scidb.cn/s/bAZZFr.

ObjectiveTo evaluate the detection specificity for clinical samples and the detection capability for standard substances of five commercially available multiplex polymerase chain reaction (PCR) nucleic acid detection kits (hereinafter referred to as the kits) for respiratory pathogens, and to provide a reference for selecting appropriate detection kits for multi-pathogen nucleic acid testing of respiratory infections. MethodsA total of 60 respiratory pathogen-positive clinical samples with known redults were selected and tested using the five kits (labeled as A, B, C, D, and E). The detection rates and Kappa coefficients were calculated to evaluate the consistency between the results from these kits and those from single-pathogen PCR kits. According to the limit of detection (LOD) provided by the kits, standard substances of respiratory pathogens (including 12 types such as influenza virus, Mycoplasma pneumoniae, and Bordetella pertussis) were diluted to four concentrations (250, 500, 1 000, and 2 000 copies·mL⁻¹). All five kits were used for detection to evaluate their respective detection capabilities. ResultsCompared with the results from single-pathogen PCR kits, the five tested kits demonstrated good consistency (all Kappa >0.80). Among them, Kit A had the highest detection rate (100.00%), followed by Kits C and E (98.33%), and then Kits B and D (95.00%). All five kits showed a relatively low false negative rate (FNR) for samples with a cycle threshold (Ct) value ≤35 (≤2.38%). However, for samples with Ct values>35, the FNR increased accordingly(average FNR=6.67%, P=0.029). Kit C exhibited the highest detection sensitivity for the tested standard substances (average LOD: 458.33 copies·mL⁻¹), followed by Kit D, then Kits A/E, and finally Kit B. ConclusionThe five multiplex PCR kits showed good consistency with single-pathogen detection results, but each had its own performance emphasis. Kit A, with the highest detection rate and high throughput, is suitable for targeted viral screening. Kit B, covering the broadest pathogen spectrum (including fungi/bacteria), is suitable for comprehensive respiratory pathogen screening. Kits C, D and E, are applicable for rapid detection. It is important to note that the detection efficacy of all kits decreases for low viral load samples with Ct values >35. In practical application, selection should be based on specific screening objectives, throughput requirements, and sample types.

ObjectiveTo construct a risk prediction model for frequent acute exacerbations of chronic obstructive pulmonary disease （COPD） under disease-syndrome combination， thus providing decision support for precise clinical intervention. MethodsA total of 2 029 patients with acute exacerbations of COPD admitted to the First Affiliated Hospital of Anhui University of Chinese Medicine from January 2020 to August 2024 were retrospectively included. These patients were classified into groups of frequent acute exacerbations （≥2 times/year） and infrequent acute exacerbations （<2 times/year） according to the hospitalization times per year. Risk factors were screened by LASSO regression combined with logistic regression， and a nomogram model was constructed. The model performance was assessed based on the area under the curve （AUC）， calibration curves， and decision curve analysis （DCA）. ResultsThe differences in baseline characteristics between the frequent acute exacerbations group （1 196 cases） and infrequent acute exacerbations group （833 cases） were not statistically significant. LASSO regression combined with multivariate logistic regression screened the following independent risk factors： body mass index （BMI）， hospitalization days， number of smoking years， place of residence， use of noninvasive ventilators， oxygen-demanding therapy， liver cirrhosis， use of systemic glucocorticosteroids， and traditional Chinese medicine syndrome （phlegm and stasis obstructing the lung）. The nomogram model showed good discrimination and calibration in both the training set （AUC=0.748） and validation set （AUC=0.774）. ConclusionThe risk prediction model for frequent acute exacerbations of COPD， integrating traditional Chinese medicine syndrome， constructed in this study has high accuracy. It can provide a scientific basis for early clinical identification of high-risk patients and individualized intervention.

This consensus focuses on the clinical application of domestic ultra-high-definition (UHD) medical endoscopes in cardiovascular surgery, addressing their clinical value, key technical aspects, and strategies for broader implementation. It traces the evolution of domestic endoscopic platforms from high-resolution imaging toward integrated advanced functionalities such as fluorescence imaging, three-dimensional visualization, and intelligent assistance. The document outlines standardized procedural steps and perioperative management pathways for minimally invasive endoscopic cardiovascular surgery and summarizes specific application scenarios and technical considerations in congenital heart disease, valvular disorders, coronary artery disease, arrhythmias, and cardiac tumors. Furthermore, recommendations are provided regarding professional training, multicenter collaboration, the establishment of clinical evaluation systems, and coordinated policy-industry support to promote standardized adoption and high-quality dissemination of domestic medical devices. Based on available evidence and expert agreement, 16 consensus statements are presented, aiming to offer authoritative and actionable guidance for clinical practice.

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Transarterial radioembolization (TARE) is a widely utilized therapeutic approach for hepatocellular carcinoma (HCC), however, the clinical implementation is constrained by the stringent preparation conditions of radioembolization agents. Herein, we incorporated the superstable homogeneous iodinated formulation technology (SHIFT), simultaneously utilizing an enhanced solvent form in a carbon dioxide supercritical fluid environment, to encapsulate radionuclides (such as ¹³¹I,¹⁷⁷Lu, or ¹⁸F) with lipiodol for the preparation of radiolipiodol. The resulting radiolipiodol exhibited exceptional stability and ultra-high labeling efficiency (≥99%) and displayed notable intratumoral radionuclide retention and in vivo stability more than 2 weeks following locoregional injection in subcutaneous tumors in mice and orthotopic liver tumors in rats and rabbits. Given these encouraging findings, ¹⁸F was authorized as a radiotracer in radiolipiodol for clinical trials in HCC patients, and showed a favorable tumor accumulation, with a tumor-to-liver uptake ratio of ≥50 and minimal radionuclide leakage, confirming the feasibility of SHIFT for TARE applications. In the context of transforming from preclinical to clinical screening, the preparation of radiolipiodol by SHIFT represents an innovative physical strategy for radionuclide encapsulation. Hence, this work offers a reliable and efficient approach for TARE in HCC, showing considerable promise for clinical application (ChiCTR2400087731).

OBJECTIVES: To investigate the effects of methylenetetrahydrofolate reductase (MTHFR) rs1801133 and γ-glutamyl hydrolase (GGH) rs11545078 gene polymorphisms on plasma concentrations and toxicity following high-dose methotrexate (MTX) therapy in children with acute lymphoblastic leukemia (ALL). METHODS: Children with ALL treated at the Xuzhou Children's Hospital of Xuzhou Medical University from January 2021 to April 2024 were selected for this study. Genotypes of MTHFR rs1801133 and GGH rs11545078 were determined using multiplex polymerase chain reaction. MTX plasma concentrations were measured by enzyme-multiplied immunoassay technique, and toxicity was graded according to the Common Terminology Criteria for Adverse Events version 5.0. The relationships between MTHFR rs1801133 and GGH rs11545078 genotypes and both MTX plasma concentrations and associated toxicities were analyzed. RESULTS: In the low-risk ALL group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 72 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05), and the GGH rs11545078 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with the occurrence of reduced hemoglobin (P<0.05), and the GGH rs11545078 genotype was associated with the occurrence of thrombocytopenia (P<0.05). CONCLUSIONS Detection of MTHFR rs1801133 and GGH rs11545078 genotypes can be used to predict increased MTX plasma concentrations and the occurrence of toxic reactions in high-dose MTX treatment of ALL, enabling timely interventions to enhance safety.
Humans ; Methotrexate/toxicity* ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood* ; Male ; Female ; Child ; Child, Preschool ; gamma-Glutamyl Hydrolase/genetics* ; Antimetabolites, Antineoplastic/adverse effects* ; Infant ; Polymorphism, Genetic ; Adolescent ; Genotype ; Polymorphism, Single Nucleotide

OBJECTIVE: To explore the clinical significance of circulating tumor DNA (ctDNA) in response evaluation and relapse monitoring for patients with primary mediastinal large B-cell lymphoma (PMBCL). METHODS: The clinical characteristics, efficacy and survival of 38 PMBCL patients in our hospital from January 2010 to April 2020 were retrospectively analyzed. The ctDNA monitoring was conducted by targeted next-generation sequencing (NGS). RESULTS: Among the 38 patients, 26 cases were female, and 32 cases were diagnosed with Ann Arbor stage I-II. The 5-year overall survival (OS) rate and progression-free survival (PFS) rate were 74.7% and 61.7%, respectively. Males and those with high aaIPI scores (3 points) had a relatively poor prognosis. The NGS results of 23 patients showed that STAT6 (65.2%), SOCS1 (56.5%), and TNFAIP3 (56.5%) were the most common mutated genes. Patients with stable disease (SD)/progressive disease (PD) exhibited enrichment in cell cycle, FoxO, and TNF signaling pathways. A total of 29 patients underwent end-of-treatment PET/CT (EOT PET/CT), and 16 of them received ctDNA monitoring with 12 negative. Among 6 patients with EOT PET/CT positive (Deauville 4), 4 underwent ctDNA monitoring, and 3 of them were negative, being still in continuous remission without any subsequent anti-tumor therapy. CONCLUSION CtDNA may be combined with PET/CT to assess efficacy, monitor relapse, and guide treatment of PMBCL.
Humans ; Circulating Tumor DNA/blood* ; Female ; Mediastinal Neoplasms ; Male ; Retrospective Studies ; High-Throughput Nucleotide Sequencing ; Prognosis ; Lymphoma, Large B-Cell, Diffuse/genetics* ; Middle Aged ; Adult ; Aged ; Neoplasm Recurrence, Local ; Mutation

E3 ubiquitin ligase is a key enzyme that determines substrate specificity during ubiquitination and plays an important role in regulating the degradation of tumor suppressor or oncogenic proteins. E3 ubiquitin ligase is involved in regulating leukemia cell differentiation, cell cycle and immune response, and it is closely related to the occurrence and development of acute myeloid leukemia (AML). Targeting highly specific E3 ubiquitin ligase can be used as an effective treatment for AML. This article reviewed the latest progress of E3 ubiquitin ligase in the diagnosis and treatment of AML, aiming to provide insights for the precise targeted therapy of this disease.
Humans ; Ubiquitin-Protein Ligases/metabolism* ; Leukemia, Myeloid, Acute/therapy*