The onset and progression of chronic heart failure （CHF） are closely associated with myocardial energy metabolism disorders， and this pathological process significantly affects patient prognosis. Traditional Chinese medicine （TCM）， grounded in time-based medical theories such as the correspondence between humans and nature and the theory of circadian flow of meridians （Ziwu Liuzhu）， exhibits intrinsic consistency with modern circadian rhythm theory， providing a unique theoretical framework for understanding and intervening in CHF from a temporal perspective. This article systematically explores the impact of circadian rhythms on energy metabolism and the potential mechanisms by which TCM active ingredients intervene in CHF through a review of relevant literature. It is found that various TCM active ingredients， including flavonoids （such as nobiletin）， alkaloids （such as berberine）， and polyphenols （such as resveratrol）， can improve mitochondrial function， promote fatty acid oxidation， enhance glucose uptake and utilization efficiency， maintain metabolic balance， and alleviate oxidative stress and inflammatory responses in myocardial cells by regulating the expression and rhythms of core circadian clock genes such as CLOCK， BMAL1， PER， and CRY. These actions thereby correct energy metabolism disorders and improve cardiac function. Further exploration of the interaction mechanisms between these components and the circadian rhythms holds promise for providing novel theoretical foundations and potential intervention strategies for the prevention and treatment of CHF.

Objective To analyze the influenza-like illness (ILI) data in Ordos City from 2017 to 2023 and conduct nucleic acid detection of the virus to understand the local influenza epidemic situation, and to provide a reliable basis for influenza prevention and control in the city. Methods Real-time quantitative polymerase chain reaction (qPCR) was used to identify virus subtypes in ILI throat swab samples. Comparisons of positive rates were conducted using the chi-square test, with a significance level of α=0.05. Results From 2017 to 2023, a total of 3,283,434 outpatient and emergency visits were recorded at the Ordos City Central Hospital, including 74,159 ILI cases, with an ILI proportion of 2.26%. The majority of ILI cases (74.43%) occurred in children aged 0~14 years old. The overall positive rate of influenza virus nucleic acid detection was 10.87%, with the highest proportion being subtype A (seasonal H3) at 43.03%. The highest detection rate was observed in the 5~14 years age group, with statistically significant differences in positive rates across age groups (χ²=155.638, P<0.001). Influenza peaks occurred mainly from November to March of the following year. From January to April, three types of influenza were prevalent alternately or mixed, while from October to December, subtype A (seasonal H3) predominated. Positive rates varied significantly across months (χ²=250.923, P<0.001). The temporal trends of ILI proportions and PCR-positive rates were consistent. Conclusion Influenza in Ordos City exhibits distinct seasonal and age distribution characteristics, with alternating or mixed circulation of three virus types. Continued efforts are needed to strengthen influenza surveillance, especially the prevention and control of influenza in infants and adolescents.

Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

Gastric cancer remains one of the most prevalent and lethal malignancies of the digestive tract worldwide,underscoring the urgent need for more effective targeted therapeutic strategies.Poly(ADP-ri-bose)polymerase(PARP)inhibitors have demonstrated remarkable efficacy in tumors with homologous recombination repair(HRR)deficiency;however,their clinical application in gastric cancer remains limited.Clinical evidence suggests that patients harboring Helicobacter pylori infection in combination with HRR gene mutations exhibit a significantly elevated risk of developing gastric cancer,thereby supporting the potential benefit of PARP inhibition in this setting.In this study,a kinase inhibitor library was screened in combination with the PARP inhibitor olaparib in gastric cancer cells.And we identify the cy-clin-dependent kinase 8/19(CDK8/19)inhibitor Senexin A as a compound that synergistically enhances the cytotoxic effect of PARP inhibition(P<0.05).Phenotypic validation using CCK-8 and colony for-mation assays demonstrated that the combination treatment significantly suppressed cellular proliferation and clonogenic potential compared to either monotherapy(P<0.0001).Mechanistically,alkaline comet assays revealed a significant increase in DNA damage in the combination treatment group relative to either single-agent group(P<0.0001),suggesting that the synergistic effect results from the exacerbation of DNA damage via impaired DNA repair mechanisms.In addition,treatment with CDK8/19 inhibitors a-lone markedly increased the formation of γH2AX and 53BP1 foci in irradiated gastric cancer cells(P<0.0001),indicating inhibition of DNA damage repair pathways.Transcriptome sequencing further re-vealed that CDK8/19 inhibition impacts critical cellular pathways,including DNA repair,cell cycle reg-ulation,and RNA splicing.Co-immunoprecipitation assays confirmed that inhibition of CDK8/19 kinase activity significantly reduces the phosphorylation level of PARP1,suggesting a potential regulatory inter-action.Immunohistochemical analysis of tumor and adjacent non-tumor tissues from gastric cancer pa-tients demonstrated that CDK8 is significantly overexpressed in tumor tissues,supporting its potential as both a prognostic biomarker and a therapeutic target.Collectively,this study elucidates a mechanistic ba-sis by which CDK8/19 inhibition enhances the sensitivity of gastric cancer cells to PARP inhibitors.These findings provide a strong rationale for the combined use of CDK8/19 and PARP inhibitors as a tar-geted therapeutic strategy and offer promising translational implications for advancing personalized medi-cine in gastric cancer treatment.

Objective To evaluate the reliability,validity,and feasibility of the diagnostic scale for toxic pathogen syndrome in heart failure(HF),and to verify its reliability and effectiveness in clinical diagnosis.Methods A cross-sectional study was conducted.Patients with HF who visited four hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,from March 1st to September 30th,2024 were selected.General information of the patients,including gender,age,smoking history,drinking history,and comorbidities,was collected.Cronbach's α coefficient,split-half reliability,and test-retest reliability were used to evaluate the reliability of the scale.Surface validity,discriminant validity,and structural validity were used to assess the validity of the scale.Acceptance rate,completion rate,and completion time were used to evaluate the feasibility.Results A total of 600 patients with HF meeting the research criteria were included,including 290 males and 310 females,with a median(IQR)age of 66.50(58.00,70.00)years.Internal consistency reliability:the Cronbach's α coefficients of the total scale and the four dimensions were all greater than 0.6,indicating a good consistency among the items of the scale.The Spearman-Brown coefficients of the total scale and the four dimensions were all greater than 0.7,indicating good stability and homogeneity within the scale.External consistency reliability:the Kappa coefficients of the total scale and the four dimensions were all greater than 0.7,indicating good external consistency of the scale.Discriminant validity evaluation:patients were divided into the toxic pathogen syndrome group(n=180)and the non-toxic pathogen syndrome group(n=420).There were no statistically significant differences in gender,age,smoking history,drinking history,and comorbidities between the two groups(P>0.05).The scores of the two groups were evaluated using the diagnostic scale for the toxic pathogen syndrome in HF.The toxic pathogen syndrome group had higher scores in all four dimensions and the total scale than the non-toxic pathogen syndrome group(P<0.01),indicating good discriminant validity of the scale.Structural validity assessment:principal component analysis was used to extract 28 factors,and a total of 7 common factors were extracted,with a total variance contribution rate of 60.554%.The absolute values of the loadings of each item were basically greater than 0.5,and the commonalities of the corresponding dimensions ranged from 52.1%to 96.5%,indicating good structural validity of the scale.The acceptance rate of the scale in this evaluation was 100%,the completion rate was 100%,and the average completion time was between 6 and 8 minutes,indicating good feasibility of the scale.Conclusion The diagnostic scale for the toxic pathogen syndrome in HF has good reliability,validity,and feasibility.

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

Hepatocellular carcinoma (HCC) expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming. Aldolase A (ALDOA) plays a prominent role in glycolysis; however, little is known about its role in HCC development. In the present study, we aim to explore how ALDOA is involved in HCC proliferation. HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout, which is consistent with ALDOA overexpression encouraging HCC proliferation. Mechanistically, ALDOA knockout partially limits the glycolytic flux in HCC cells. Meanwhile, ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase; ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function. A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun, and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells. In HCC patients, the expression level of ALDOA was correlated with the phosphorylation level of c-Jun (Thr93) and poor prognosis. Remarkably, hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models, and the knockdown of A ldoa strikingly decreased HCC development in vivo. Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription, opening additional avenues for anti-cancer therapies.

OBJECTIVE: This study aimed to investigate possible serum 25-hydroxyvitamin D [25(OH)D] cutoffs for the associations between 25(OH)D and Bone turnover markers (BTMs), and how GC gene variation influences such cutoffs in Chinese women of childbearing age. METHODS: In total, 1,505 non-pregnant or non-lactating women (18-45 years) were recruited from the 2015 Chinese Adult Chronic Disease and Nutrition Surveillance. Serum 25(OH)D, osteocalcin (OC), procollagen type 1 N-terminal propeptide (P1NP), β-CrossLaps of type 1 collagen containing cross-linked C-telopeptide (β-CTX), and single nucleotide polymorphisms were determined. Locally weighted regression and smoothing scatterplot and segmented regression were performed to estimate the 25(OH)D thresholds. RESULTS: The median serum 25(OH)D was 16.63 (11.96-22.55) ng/mL and the prevalence of low serum 25(OH)D (< 12 ng/mL) was 25.2%. Women with the lowest 25(OH)D had the highest β-CTX. After adjustment for the confounders, 25(OH)D cutoffs for OC [14.04 (12.84-15.23) ng/mL], β-CTX [13.94 (12.49-15.39) ng/mL], and P1NP [13.87 (12.37-15.37) ng/mL] in the whole population, cutoffs for OC [12.30 (10.68-13.91) ng/mL], β-CTX [12.23 (10.22-14.23) ng/mL], and P1NP [11.85 (10.40-13.31) ng/mL] in women with the GC rs2282679 G allele, and cutoffs for OC [12.75 (11.81-13.68) ng/mL], β-CTX [13.05 (11.78-14.32) ng/mL], and P1NP [12.81 (11.57-14.06) ng/mL] in women with the GC rs2282679 T allele, were observed. Below these cutoffs, BTMs were negatively associated with 25(OH)D, while above these cutoffs, BTMs plateaued. CONCLUSION In Chinese women of childbearing age, there were thresholds effect of serum 25(OH)D concentrations on BTMs. The results indicated that serum 25(OH)D concentrations < 13.87 ng/mL in this population had adverse influences on maintaining bone remodeling. BTMs were suppressed at a relatively lower serum 25(OH)D in women with the GC rs2282679 G allele compared with those with the T allele.
Humans ; Female ; Vitamin D/blood* ; Adult ; Middle Aged ; Polymorphism, Single Nucleotide ; Adolescent ; Young Adult ; China ; Biomarkers/blood* ; Bone Remodeling/genetics* ; Vitamin D-Binding Protein/genetics* ; Procollagen/blood* ; Osteocalcin/blood* ; Peptide Fragments/blood* ; East Asian People

Objective:To investigate the selection of treatment methods for renal tumors in pilots as well as the clinical significance of robot-assisted surgery by summarizing the process of robot-assisted surgery in the treatment of renal cell carcinoma in a pilot.Methods:The diagnosis, robot-assisted surgery and aeromedical assessment of a pilot with renal cell carcinoma were reported, and the related literature was reviewed.Results:The patient was a 44-year-old male transporter pilot, who was diagnosed with a left renal mass in the middle-lower pole of the kidney during a routine abdominal CT scan. After detailed preoperative evaluation that ruled out the possibility of distant metastasis and other surgical contraindications, the patient underwent robot-assisted laparoscopic partial nephrectomy in August 2022. The postoperative recovery went well, and renal function remained within normal limits at follow-ups. In March 2023, the pilot was concluded as qualified for flight after aeromedical assessment.Conclusions:Robot-assisted partial nephrectomy can significantly reduce surgical trauma, lower the risk of complications, and maximally preserve renal function. It is a good approach to renal tumors in pilots who can recover quickly.

Objective:To explore the diagnosis and treatment of the flying personnel with asymptomatic primary hyperparathyroidism (aPHPT) and the principles of aeromedical assessments.Methods:The clinical data of a helicopter navigator with aPHPT was retrospectively analyzed, and the related literature was reviewed.Results:A helicopter navigator was diagnosed with hyperplasie parathyroide or parathyroid adenoma in November 2020. In March 2021, the patient had his parathyroid adenoma explored and excised. Postoperatively, levels of parathyroid hormone (PTH) and serum calcium were mildly elevated, but without typical clinical manifestations of primary hyperparathyroidism, so temporary grounding was warranted. In June 2023, the patient returned to the hospital for re-examination, where PTH and serum calcium remained elevated. Parathyroid static imaging showed a focal concentration in the right lower parathyroid region, which was consistent with the manifestation of parathyroid adenoma so that the patient was diagnosed with aPHPT, resulting in temporary grounding. In June 2024, the patient was admitted to the Department of Endocrinology, Air Force Medical Center for aeromedical assessment, where PTH and serum calcium showed mild elevation, without such complications as urinary calculi or osteoporosis. The patient was diagnosed with aPHPT with no indication for surgery. Dynamic follow-up and monitoring of parathyroid-related indicators were recommended. The patient was determined as eligible for flight via aeromedical assessment and has flown safely for 200 h so far.Conclusions:For flying personnl with aPHPT, it is crucial to identify potential risks of disease progression and find out whether parathyroidectomy can improve clinical symptoms and surgical outcomes. The aeromedical assessment of aPHPT flying personnel should involve comprehensive assessments of conditions and dynamic monitoring of biochemical indicators, and be individualized according to the type of aircraft and flight duties.