OBJECTIVE: Circadian rhythm disruption (CRD) is a risk factor that correlates with poor prognosis across multiple tumor types, including hepatocellular carcinoma (HCC). However, its mechanism remains unclear. This study aimed to define HCC subtypes based on CRD and explore their individual heterogeneity. METHODS: To quantify CRD, the HCC CRD score (HCCcrds) was developed. Using machine learning algorithms, we identified CRD module genes and defined CRD-related HCC subtypes in The Cancer Genome Atlas liver HCC cohort (n = 369), and the robustness of this method was validated. Furthermore, we used bioinformatics tools to investigate the cellular heterogeneity across these CRD subtypes. RESULTS: We defined three distinct HCC subtypes that exhibit significant heterogeneity in prognosis. The CRD-related subtype with high HCCcrds was significantly correlated with worse prognosis, higher pathological grade, and advanced clinical stages, while the CRD-related subtype with low HCCcrds had better clinical outcomes. We also identified novel biomarkers for each subtype, such as nicotinamide n-methyltransferase and myristoylated alanine-rich protein kinase C substrate-like 1. CONCLUSION We classify the HCC patients into three distinct groups based on circadian rhythm and identify their specific biomarkers. Within these groups greater HCCcrds was associated with worse prognosis. This approach has the potential to improve prediction of an individual's prognosis, guide precision treatments, and assist clinical decision making for HCC patients. Please cite this article as: Li XJ, Chang L, Mi Y, Zhang G, Zhu SS, Zhang YX, et al. Integrated-omics analysis defines subtypes of hepatocellular carcinoma based on circadian rhythm. J Integr Med. 2025; 23(4): 445-456.
Humans ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; Circadian Rhythm/genetics* ; Prognosis ; Male ; Female ; Biomarkers, Tumor/genetics* ; Middle Aged ; Machine Learning ; Computational Biology

The plant AT-rich sequence and zinc-binding protein (PLATZ) family is composed of plant-specific zinc finger-like transcription factors, which play important roles in plant growth, development, and stress tolerance. In this study, to gain a better understanding of the PLATZ gene in C. sinensis and elucidate its response under drought and high temperature conditions, the PLATZ gene family of the C. sinensis cultivar 'Tieguanyin' was systematically identified, and a total of 12 CsPLATZ family members were identified. Expasy online and other bioinformatics tools were used to analyze the members of the PLATZ gene family in terms of protein physicochemical properties, phylogenetic relationships, cis-acting elements, gene structures, and intra- and inter-species collinearity. The results of phylogenetic analysis classified the CsPLATZ family members into 2 subfamilies. The conserved domains and gene structures of PLATZ family members within the same subfamily had a high degree of consistency, whereas a certain degree of diversity was observed among the subfamilies. Twelve PLATZ genes were unevenly distributed across 7 chromosomes of C. sinensis and the promoter regions of these genes had multiple cis-acting elements related to hormone and stress responses. The collinearity analysis showed that there were 4 pairs of duplication events in the CsPLATZ gene family, all of which were segmental duplications. Based on this gene family, C. sinensis had a closer evolutionary relationship with A. thaliana than with O. sativa. The transcriptome analysis showed that the expression levels of CsPLATZ family members varied in different tissue samples of C. sinensis. 6 genes (CsPLATZ-1, CsPLATZ-2, CsPLATZ-3, CsPLATZ-4, CsPLATZ-6, and CsPLATZ-8) with high expression in shoots, young leaves, and roots were selected for high temperature and drought stress treatments, and their expression was quantified by qRT-PCR. The results indicated that the six genes might play important roles in the response to drought stress. In addition, CsPLATZ-2 and CsPLATZ-8 might have important functions in the response to high temperature stress. The results of this study will contribute to a better understanding of the biological functions of PLATZ genes and their possible roles in the growth, development, and stress responses of C. sinensis.
Droughts ; Camellia sinensis/physiology* ; Phylogeny ; Gene Expression Regulation, Plant ; Plant Proteins/genetics* ; Stress, Physiological/genetics* ; Multigene Family ; Transcription Factors/genetics* ; Hot Temperature ; Genes, Plant

Inflammatory bowel disease (IBD) is characterized by chronic relapsing intestinal inflammation and encompasses ulcerative colitis (UC) and Crohn's disease (CD). IBD has emerged as a global healthcare problem. Clinically efficacious therapeutic agents are deficient. This study concentrates on models of ulcerative colitis with the objective of discovering novel therapeutic strategies. Previous investigations have established that schisandrin A demonstrates anti-inflammatory effects in vitro, concurrently enhancing the transcriptional activity of farnesoid X receptor (FXR). FXR inversely modulates the transcriptional activity of NF-κB, which has an important role in regulating inflammatory responses. Consequently, the current study was to explore the safeguarding influence of schisandrin A on ulcerative colitis and delineate the mechanism by which it regulates this effect through the FXR signaling pathway. The effect of schisandrin A on the mRNA levels of inflammatory factors was evaluated in RAW264.7 cells. The dual luciferase reporter gene assay was used to verify the relationship between schisandrin A and FXR targeting. The animal experiments were performed in accordance with the regulations of the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine (approval No. PZSHUTCM2304250005). Acute ulcerative colitis was induced in wild-type or FXR knockout C57BL/6 mice by drinking 3% dextran sodium sulfate (DSS) for 7 days, and schisandrin A was administered via gavage for a continuous treatment period of 7 days. The body weight and faecal were monitored daily. The mRNA levels of inflammatory factors in colon tissue and FXR target genes were measured by RT-qPCR. The findings revealed that schisandrin A, in vitro, impeded the lipopolysaccharide (LPS)-induced elevation in mRNA levels of inflammatory factors and schisandrin A could augment transcriptional activity of FXR. In wild-type mice, schisandrin A significantly improved weight loss, colon shortening, loose stools and blood in stools in mice with acute ulcerative colitis, and schisandrin A significantly reduced the expression of pro-inflammatory factors genes and significantly increased the expression of FXR target genes in colon tissues. In FXR knockout mice, the administration of schisandrin A failed to yield ameliorative effect on acute ulcerative colitis in mice. In conclusion, schisandrin A can reduce intestinal inflammation through the FXR signaling pathway to alleviate acute ulcerative colitis in mice. Implications arise that Schisandra lignans could serve as lead compounds for drug development aimed at inflammatory bowel disease.

ObjectiveTriple-negative breast cancer (TNBC) is the breast cancer subtype with the worst prognosis, and lacks effective therapeutic targets. Colony stimulating factors (CSFs) are cytokines that can regulate the production of blood cells and stimulate the growth and development of immune cells, playing an important role in the malignant progression of TNBC. This article aims to construct a novel prognostic model based on the expression of colony stimulating factors-related genes (CRGs), and analyze the sensitivity of TNBC patients to immunotherapy and drug therapy. MethodsWe downloaded CRGs from public databases and screened for differentially expressed CRGs between normal and TNBC tissues in the TCGA-BRCA database. Through LASSO Cox regression analysis, we constructed a prognostic model and stratified TNBC patients into high-risk and low-risk groups based on the colony stimulating factors-related genes risk score (CRRS). We further analyzed the correlation between CRRS and patient prognosis, clinical features, tumor microenvironment (TME) in both high-risk and low-risk groups, and evaluated the relationship between CRRS and sensitivity to immunotherapy and drug therapy. ResultsWe identified 842 differentially expressed CRGs in breast cancer tissues of TNBC patients and selected 13 CRGs for constructing the prognostic model. Kaplan-Meier survival curves, time-dependent receiver operating characteristic curves, and other analyses confirmed that TNBC patients with high CRRS had shorter overall survival, and the predictive ability of CRRS prognostic model was further validated using the GEO dataset. Nomogram combining clinical features confirmed that CRRS was an independent factor for the prognosis of TNBC patients. Moreover, patients in the high-risk group had lower levels of immune infiltration in the TME and were sensitive to chemotherapeutic drugs such as 5-fluorouracil, ipatasertib, and paclitaxel. ConclusionWe have developed a CRRS-based prognostic model composed of 13 differentially expressed CRGs, which may serve as a useful tool for predicting the prognosis of TNBC patients and guiding clinical treatment. Moreover, the key genes within this model may represent potential molecular targets for future therapies of TNBC.

AIM: To investigate the efficacy of lacrimal duct laser dacryoplasty combined with intubation and postoperative meibomian gland treatment in patients with chronic dacryocystitis complicated by meibomian gland dysfunction.METHODS: Data were collected from 128 patients with chronic dacryocystitis complicated by meibomian gland dysfunction treated at Xi'an No.1 Hospital from March 2021 to December 2022. All patients underwent lacrimal duct laser dacryoplasty combined with intubation. Postoperatively, those patients were randomly divided into two groups: group A(64 cases, without meibomian gland treatment)and group B(64 cases, with meibomian gland treatment). The lacrimal intubation was removed at 3 mo after surgery to evaluate the patency rate of lacrimal irrigation. Additionally, changes in the ocular surface disease index(OSDI)score, non-invasive tear film break-up time, tear meniscus height, conjunctival hyperemia analysis, meibomian gland analysis, tear lipid layer thickness, tear ferning test, and conjunctival impression cytology were compared between the two groups.RESULTS: The lacrimal irrigation patency rates in the group A and group B were 78.1% and 81.2% respectively, with no statistically significant difference between the two groups(P>0.05); compared with the group A, group B showed a significant extension in non-invasive tear breakup time at 3 mo after surgery, and the OSDI score, conjunctival hyperemia analysis, tear ferning test and conjunctival impression cytology grading were all significantly decreased(all P<0.05), while there was no significant difference in tear meniscus height, tear lipid layer thickness and meibomian gland loss score between the two groups(all P>0.05).CONCLUSION: Comprehensive treatment for patients with chronic dacryocystitis combined with meibomian gland dysfunction have improved patients' comfort, tear film stability, and reduces local inflammatory response. It is important to simultaneously address ocular surface microenvironment abnormalities during surgical treatment to achieve satisfactory efficacy.

Objective:To evaluate the incidence of arrhythmias and electrocardiographic (ECG) characteristics in cancer patients treated with immune checkpoint inhibitors (ICIs).Methods:This was a cohort study conducted in the Fourth Hospital of Hebei Medical University. Cancer patients initiating ICIs treatments from November 2020 to September 2022 were included in this study. Baseline 12-leads ECG before ICIs initiation and post-treatment ECG were analyzed. An abnormal ECG was defined as the presence of any of the following changes: sinus arrhythmias, atrial fibrillation, atrial flutter, paroxysmal supraventricular tachycardia, ventricular tachycardia, premature contractions, conduction disorder, and ST-T changes.Results:A total of 87 patients were enrolled, aged 63 (57, 68) years, with 66 (75.9%) males. And 44.8% (39/87) of patients presented with at least one confirmed cardiovascular disease or cardiovascular risk factor at baseline. The incidence of abnormal ECG increased from 31.0% (27/87) at baseline to 65.5% (57/87) after receiving (5.0±2.7) cycles of ICIs treatment ( P<0.001). The incidence of sinus arrhythmias was significantly increased after ICIs treatment (23.0% (20/87) vs. 9.2% (8/87), P=0.023), of which only the incidence of sinus tachycardia was significantly increased (11.5% (10/87) vs. 2.3% (2/87), P=0.039). There was also a significantly increased incidence of ST-T changes after ICIs treatment (31.0% (27/87) vs. 17.2% (15/87), P=0.012), which mainly attributed to the T wave changes (29.9% (26/87) vs. 13.8% (12/87), P=0.001). The incidence of premature contractions was also significantly increased after ICIs treatment (9.2% (8/87) vs. 0, P=0.008). Additionally, compared with baseline, the P wave axis was significantly increased after ICIs treatment ((56.94±21.01)° vs. (52.00±22.69)°, P=0.043). After ICIs treatment, the heart rate was significantly increased ((79.07±15.37) beats/min vs. (75.64±13.37) beats/min, P=0.029). Sokolow-Lyon index ((2.21±0.81)mV vs. (2.33±0.75)mV, P=0.138), QTc interval ((431.44±36.04)ms vs. (428.00±30.05)ms, P=0.415) all showed signs of change after treatment, but did not reach the traditional significant level. Conclusions:The incidence of abnormal ECG is significantly increased after ICIs treatment, especially for sinus tachycardia, premature contractions and T wave changes; the P wave axis and heart rate is also significantly increased after treatment. It is important to perform regular ECG monitoring in patients receiving ICIs treatment.

Osteoporosis is an important cause of internal fixation loosening after spinal surgery.Cement-augmented pedicle screw instru-mentation(CAPSI)technique is the most widely used technique in clinical practice to improve the stability of pedicle screw,mainly applied in osteoporosis and revision surgery,which included conventional solid pedicles crews and fenestrated/cannulated pedicle screws technique.CAPSI technique may cause cement leakage and pulmonary embolism,and there is no consensus on its indications or technical points.Therefore,this article reviews the research progress of CAPSI,in order to provide relevant reference for clinical practice.

Oral diseases are usually caused by external physical and chemical factors,the invasion of pathogens,dento-maxillofacial deformities and systemic diseases.Oral infections and orofacial pain triggered by oral diseases seriously reduce the quality of life.Pyroptosis is a kind of programmed cell death,which is characterized by swelling of the cell until the cell membrane ruptures,releasing the cell contents and activating a strong inflammatory response.Previous studies have shown that pyroptosis is widely involved in the occurrence and development of oral diseases.In this review,four types of cellular pyroptosis pathways are described in detail,including the canonical pathway,non-canonical pathway,caspase-3/8 mediated pathway and caspase independent pathway.Different pyroptosis pathways form complex signal networks,which regulate the functions of periodontal membrane cells,gingival fibroblasts,macrophages and other cells in the oral cavity,thus affecting the occurrence and development of oral diseases.This review summarizes the latest research about the pathways of pyroptosis and its roles in oral diseases,aiming to provide a theoretical basis and direction for searching effective methods to treat and prevent oral diseases.

Perivascular adipose tissue(PVAT),attached to the adventitia,is a special functional layer of the vascular wall structure.PVAT exists around most blood vessels and is mainly composed of adipocytes,fibroblasts,stem cells,mast cells and nerve cells.PVAT not only participates in energy metabolism,but also has secretory function.It plays an important role in maintaining vascular structure and regulating vascular function.Atherosclerosis is a chro-nic metabolic syndrome characterized by endothelial dysfunction,lipid deposition,and inflammatory infiltration,which is closely associated with obesity.This paper reviews the role of PVAT in atherosclerosis.