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

OBJECTIVES: To study the clinical and genetic characteristics of osteopetrosis (OPT) in children. METHODS: A retrospective analysis was performed on the clinical data of 14 children with OPT. Whole-exome sequencing was used to detect pathogenic genes, and clinical phenotypes and genotypic features were summarized. RESULTS: Among the 14 children (10 males and 4 females), the median age at diagnosis was 8 months. Clinical manifestations included systemic osteosclerosis (14 cases, 100%), anemia (12 cases, 86%), infections (10 cases, 71%), thrombocytopenia (9 cases, 64%), hepatosplenomegaly (8 cases, 57%), and developmental delay (5 cases, 36%). Malignant osteopetrosis (MOP) cases had lower platelet counts, creatine kinase isoenzyme, and serum calcium levels, but higher white blood cell counts, lactate dehydrogenase, and alkaline phosphatase levels compared to non-MOP cases (P<0.05). Genetic testing identified 15 variants in 12 patients, including 8 variants in the CLCN7 gene (53%), 6 in the TCIRG1 gene (40%), and 1 in the TNFRSF11A gene (7%). Three novel CLCN7 variants were identified: c.2351G>C, c.1215-43C>T, and c.1534G>A. All four patients with TCIRG1 variants exhibited MOP clinical phenotypes. Of the seven patients with CLCN7 variants, 4 presented with intermediate OPT, 2 with benign OPT, and 1 with MOP. CONCLUSIONS Clinical phenotypes of OPT in children are heterogeneous, predominantly involving CLCN7 and TCIRG1 gene variants, with a correlation between clinical phenotypes and genotypes.
Humans ; Osteopetrosis/genetics* ; Male ; Female ; Infant ; Child, Preschool ; Retrospective Studies ; Vacuolar Proton-Translocating ATPases/genetics* ; Child ; Chloride Channels/genetics* ; Mutation ; Receptor Activator of Nuclear Factor-kappa B

OBJECTIVE: To investigate the effects of low-dose irradiated autologous peripheral blood reinfusion (LDIAPBR) on a rat model of radiation-induced leukopenia. METHODS: The rats were randomly divided into four groups. In the LDIAPBR group, LDIAPBR was performed 1 day before modeling (10% of the total circulating blood volume was withdrawn, irradiated with 100 mGy ex vivo, and completely reinfused). Meanwhile, the normal group and model group only underwent blood withdrawal and reinfusion of the same proportion without blood irradiation. Except for the normal group, all groups were subjected to 1 Gy X-ray whole-body irradiation to establish a radiation-induced leukopenia rat model. The positive drug group received subcutaneous injection of rhG-CSF after modeling. It was monitored that the general condition of the rats, peripheral blood cell counts, immune organ indices, bone marrow nucleated cell counts and viability, and the pathological analysis of bone marrow sections was conducted. RESULTS: The LDIAPBR group exhibited significant improvements in overall condition compared to the model group. Notably, compared with the model group, peripheral blood leukocyte and lymphocyte counts were markedly higher in the LDIAPBR group. Furthermore, there was a significant increase in both the number and viability of nucleated cells in the bone marrow. Pathological examination of bone marrow sections revealed increased nucleated cell density and reduced cavity area in the LDIAPBR group. CONCLUSION LDIAPBR can effectively improve hematological parameters and bone marrow hematopoietic function in a rat model of radiation-induced leukopenia, providing a new approach for the prevention and treatment of radiation-related injuries.
Animals ; Leukopenia/prevention & control* ; Rats ; Blood Transfusion, Autologous ; Whole-Body Irradiation ; Radiation Injuries, Experimental/therapy*

Objective:To investigate the effect of early enteral nutrition on intestinal function in patients with complicated intra-abdominal infection.Methods:In this study,a prospective single-center randomized controlled trial was used to select 88 patients with severe abdominal infections in the surgical intensive care ward from January 2021 to December 2023.Among them,65 patients were eligible and were randomly divided into 33cases in the intervention group(who received early enteral nutrition),and 32cases in the control group(who did not receive early enteral nutrition).The clinical baseline characteristics of the two groups,conditions such as abdominal distension and diarrhea during enteral nutrition,intra-abdominal pressure,the time to reach the standard of complete enteral nutrition,and the indexes of pre-albumin,CRP,and leukocyte count on the third and the seventh day postoperative day were observed.The t-test was used to compare between groups for normally distributed measures.The Mann-Whitney U test was used to compare between groups for skewed measures.The χ2 test or continuity-corrected χ2 test was used to compare the count data between groups.Repeated measures data were analyzed by repeated measures ANOVA.Results:The clinical baseline characteristics of the two groups were completely matched;There were significant differences in the changes of intra-abdominal pressure over time between the two groups(Fgroup=9.665,P=0.004),There were significant differences in the changes of intra-abdominal pressure over time between the two intervention group(Ftime=64.124,P<0.001)and the control group.and the trend of intra-abdominal pressure reduction in the intervention group was more significant than that in the control group(Finteractive=3.938,P=0.023);The time required for the recovery of bowel sounds was significantly shorter in the experimental group than in the control group[(19.5±3.5)h vs(35.3±4.5)h,P<0.001,t=15.829];there was no significant difference in the frequency of abdominal distention,vomiting and aspiration between the two groups(P>0.05),and the difference in the frequency of diarrhea was statistically significant(P=0.003);The time to reach the standard of enteral nutrition in the intervention group was shorter than that in the control group[(6.3±1.2)d vs(7.4±1.5)d,P=0.002];The total hospital stay of the intervention group was significantly shorter than that of the control group[(11±3.2)d vs(14±4.1)d,P=0.007].The prealbumin(0.21±0.2,0.28±0.2)g/L,CRP(175.5±23.6,45.4±14.5)mg/L,and white blood cell count(11.7±2.9,9.1±3.5)109/L of the intervention group on the 3rd and 7th days after surgery were significantly improved compared with those of the control group(P<0.05).Conclusion:Early enteral nutrition can effectively promote the recovery of intestinal function in patients with complicated intra-abdominal infection.

Antibiotics are widely used in clinical treatment of bacterial infection diseases and in the breeding of livestock,poultry and aquatic products.However,the irrational and excessive use of antibiotics not only leads to the emergence of drug-resistant superbugs,but also the antibiotics discharged into the environment pose a significant threat to the environment and human health.Antibiotics have been included in the list of key new pollutants to be controlled.Therefore,the detection of residual antibiotics in environmental media and food is of vital importance for protecting the environment and public health.Among various antibiotic detection methods,electrochemical sensors have attracted extensive attention due to their high sensitivity,low cost,simplicity and rapidity.Appropriate modification of the electrode surface can enhance the sensitivity of electrochemical sensors,reduce interference and expand the detection range.Metal-organic frameworks(MOFs)materials have the advantages of rich types,adjustable structure and activity,high specific surface area and high porosity,and show great application potential in the field of electrochemical sensing.This paper first introduces the synthesis methods of MOFs,reviews the research progress of MOFs-modified electrodes for detection of common antibiotics by electrochemical sensors,and finally looks forward to their future development trends in the field of rapid antibiotic detection.

Klebsiella pneumoniae is a widespread Gram-negative bacterium in Asia, and the emergence of antibiotic-resistant strains has significantly complicated treatment strategies. Traditional Chinese medicine, which has made remarkable contributions to public health in Asia for thousands of years, may offer promising antibacterial strategies. Chinese herbal medicine (CHM), the primary therapeutic modality of traditional Chinese medicine, exhibits antimicrobial activity, modulates the immune system, and has the potential to reverse antibiotic resistance through various mechanisms. However, no review has comprehensively summarized the efficacy and underlying mechanisms of CHM in treating antibiotic-resistant K. pneumoniae infections. In this study, we conducted a comprehensive review of relevant literatures published up to 2025, using the keywords “Klebsiella pneumoniae,” “traditional Chinese medicine,” and “Chinese herbal medicine” across databases including PubMed, Web of Science, ScienceDirect, and China National Knowledge Infrastructure. This review first introduces the taxonomy, virulence factors, and antibiotic resistance profile of K. pneumoniae. We then summarize CHM formulas, extracts, and active ingredients with reported antibacterial effects against K. pneumoniae, including their minimum inhibitory concentrations and mechanisms. Additionally, we highlight CHM interventions that enhance host immune responses and alleviate symptoms associated with K. pneumoniae infections. Furthermore, combining CHM with antibiotics represents a novel strategy to enhance antibiotic efficacy and combat resistance. We therefore summarize the synergistic effects and mechanisms of CHM-antibiotic combinations. Overall, this review underscores the multifaceted therapeutic potential of CHM and its active ingredients, including direct antibacterial action, immune modulation, and synergy with conventional antibiotics, providing an integrative approach to address the global challenge of antimicrobial resistance.

In clinical practice, antibiotics have historically been utilized for the treatment of pathogenic bacteria. However, the gradual emergence of antibiotic resistance among bacterial strains has posed a significant challenge to this approach. In 2022, Escherichia coli, a Gram-negative bacterium renowned for its widespread pathogenicity and high virulence, emerged as the predominant pathogenic bacterium in China. The rapid emergence of antibiotic-resistant E. coli strains has rendered antibiotics insufficient to fight E. coli infections. Traditional Chinese medicine (TCM) has made remarkable contributions to the health of Chinese people for thousands of years, and its significant therapeutic effects have been proven in clinical practice. In this paper, we provide a comprehensive review of the advances and mechanisms of TCM and its active ingredients against antibiotic-resistant E. coli infections. First of all, this review introduces the classification, antibiotic resistance characteristics and mechanisms of E. coli. Then, the TCM formulas and extracts are listed along with their active ingredients against E. coli, including extraction solution, minimum inhibitory concentration (MIC), and the antibacterial mechanisms. In addition, there is growing evidence supporting the synergistic therapeutic strategy of combining TCM with antibiotics for the treatment of antibiotic-resistant E. coli infections, and we provide a summary of this evidence and its underlying mechanisms. In conclusion, we present a comprehensive review of TCM and highlight its potential and advantages in the prevention and treatment of E. coli infections. We hold the opinion that TCM will play an important role in global health, pharmaceutical development, and livestock farming in the future.

Contrast-free percutaneous coronary intervention demonstrates significant value in reducing contrast-associated risks.This article reports a case of a patient with iodine contrast allergy and complex coronary artery disease(involving the left main stem,left anterior descending artery,and diagonal branch),who successfully underwent contrast-free percutaneous coronary intervention(PCI)through the integration of CT angiography(CCTA),intravascular ultrasound(IVUS),and fractional flow reserve(FFR)technology.Preoperative CCTA delineated the anatomy and planned the procedural approach.Intraoperatively,IVUS assessed plaque burden and vascular remodeling,precisely guiding stent selection and positioning.FFR was combined to evaluate the functional significance of the left main stem lesion and the ischemic significance of the specific stenosis in the left anterior descending artery.Post-procedural assessment evaluated stent result and the degree of flow limitation in the diagonal branch.Through"structure-function"dual optimization,revascularization of the left anterior descending artery was achieved using a single-stent strategy,avoiding intervention on the left main stem.This case confirms that multi-modality imaging techniques can safely manage complex lesions,significantly reduce contrast volume,and are suitable for high-risk patients with allergies or renal insufficiency.Future efforts should focus on standardizing technical protocols and accumulating evidence-based evidence to facilitate the clinical implementation of contrast-free interventions.

In clinical practice,antibiotics have historically been utilized for the treatment of pathogenic bacteria.However,the gradual emergence of antibiotic resistance among bacterial strains has posed a significant challenge to this approach.In 2022,Escherichia coli,a Gram-negative bacterium renowned for its widespread pathogenicity and high virulence,emerged as the predominant pathogenic bacterium in China.The rapid emergence of antibiotic-resistant E.coli strains has rendered antibiotics insufficient to fight E.coli infections.Traditional Chinese medicine(TCM)has made remarkable contributions to the health of Chinese people for thousands of years,and its significant therapeutic effects have been proven in clinical practice.In this paper,we provide a comprehensive review of the advances and mechanisms of TCM and its active ingredients against antibiotic-resistant E.coli infections.First of all,this review in-troduces the classification,antibiotic resistance characteristics and mechanisms of E.coli.Then,the TCM formulas and extracts are listed along with their active ingredients against E.coli,including extraction solution,minimum inhibitory concentration(MIC),and the antibacterial mechanisms.In addition,there is growing evidence supporting the synergistic therapeutic strategy of combining TCM with antibiotics for the treatment of antibiotic-resistant E.coli infections,and we provide a summary of this evidence and its underlying mechanisms.In conclusion,we present a comprehensive review of TCM and highlight its potential and advantages in the prevention and treatment of E.coli infections.We hold the opinion that TCM will play an important role in global health,pharmaceutical development,and livestock farming in the future.

Objective:To investigate the status of sedentary behavior and its influencing factors among inpatients with stable schizophrenia, providing empirical evidence for developing interventions to reduce sedentary behavior.Methods:A cross-sectional survey design was used to prospectively collect clinical data from 166 inpatients with stable schizophrenia (97 males, 69 females, mean age 56.4±8.4 years) hospitalized at the Shanghai Mental Health Center affiliated with Shanghai Jiao Tong University School of Medicine from February 2024 to May 2024. Sedentary behavior time was assessed using the Sedentary Behavior Questionnaire (SBQ), daily step count was measured via pedometers, and negative schizophrenic symptoms were evaluated using the Scale for the Assessment of Negative Symptoms (SANS). Patients were divided into a non-sedentary behavior group (≥5 000 steps/day, 66 cases) and a sedentary behavior group (<5 000 steps/day, 100 cases). Clinical variables were compared between the two groups, and binary logistic regression was used to identify influencing factors of sedentary behavior.Results:Stable inpatients with schizophrenia exhibited high levels of sedentary behavior, with an average daily sedentary time of (8.03±2.33) hours and a median daily step count of 3 352 (1 258-5 506) steps. Significant differences were observed between sedentary and non-sedentary behavior groups in Age ( t=-2.38),hospitalization duration ( Z=-1.53),blunted affect ( t=-8.37),poverty of thought ( t=-2.45),avolition ( t=-2.45),impoverished interests/social engagement ( t=-2.41),abdominal obesity ( χ2=9.18),and open vs. restricted hospital/wards environment ( χ2=8.88)(all P<0.05). Binary logistic regression analysis identified that hospital/wards environment ( OR=0.314, 95 %CI: 0.125-0.787),hospitalization duration ( OR=1.001, 95 %CI: 1.000-1.001),and the negative symptom of blunted affect ( OR=3.256, 95 %CI: 1.960-5.407)(all P<0.05) were significantly influencing factors for sedentary behavior in patients with stable schizophrenia. Conclusion:Hospitalized patients with stable schizophrenia exhibit high levels of sedentary behavior. Hospital/wards environment and blunted affect are significant factors influencing sedentary behavior.