ObjectiveTo investigate the mechanism of salt processing of Psoraleae Fructus （PF） through modern analytical techniques and biotechnology， focusing on its effects related to hepatotoxicity and anti-osteoporosis activity. MethodsThe zebrafish model was utilized to evaluate the impact of PF and salt-processed Psoraleae Fructus （SPF） on the hepatotoxicity （using 134.17 ， 178.89， 268.34 mg·L^-1 as low， medium， and high dose groups of PF， 135.04， 180.06， 270.08 mg·L^-1 as low， medium， and high dose groups of SPF， respectively） and anti-osteoporotic activity （using 33.54 ， 67.08 and 134.17 mg·L^-1 as low， medium， and high dose groups of PF， 33.76， 67.52， 135.04 mg·L^-1 as low， medium， and high dose groups of SPF， respectively）， which was using alizarin red skull staining of zebrafish as an indicator of different batches of PF. The specific dosage of a batch of PF was taken as an example. Then ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry（UPLC-Q-TOF-MS） analysis was employed to identify the chemical composition of PF before and after salt processing， and PCA， OPLS-DA， and independent sample t-test were used to elucidating the compositional changes associated with the effects of salt processing on hepatotoxicity and anti-osteoporosis activity. ResultsUnder specific conditions， PF induced notable hepatotoxicity in zebrafish while simultaneously demonstrating protective effect against prednisolone-induced osteoporosis. In comparison to PF， SPF showed alleviated hepatotoxicity while retaining significant anti-osteoporosis activity. UPLC-Q-TOF-MS analysis revealed that after salt processing， the overall chemical composition of PF showed a downward trend， with 69 components showing a decrease in content， represented by psoralen， and 13 components showing an increase， represented by 4′-O-methyl psoralen B. Further multivariate statistical analysis revealed 11 key differential components before and after salt processing of PF， including psoralen and bakuchiol. ConclusionSalt processing effectively diminishes hepatotoxicity without impairing therapeutic efficacy against osteoporosis of PF， which may be related to the compositional changes before and after salt processing of PF and provides key evidence to reveal the scientific significance of salt processing of PF.

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

OBJECTIVE: Asthma imposes a significant global health burden. This study examines changes in the asthma-related disease burden from 1990 to 2021 and projects future burdens for 2050 under different scenarios. METHODS: Using data from the Global Burden of Disease 2021 study, we analyzed asthma incidence, prevalence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2021. We projected the disease burden for 2050 based on current trends and hypothetical scenarios in which all risk factors are controlled. Temporal trends in age-standardized incidence, prevalence, mortality, and DALY rates were explored using Annual Percent Change. RESULTS: In 2021, the age-standardized rates for asthma incidence, prevalence, mortality, and DALYs in China were 364.17 per 100,000 (95% uncertainty interval [ UI]: 283.22-494.10), 1,956.49 per 100,000 (95% UI: 1,566.68-2,491.87), 1.47 per 100,000 (95% UI: 1.15-1.79), and 103.76 per 100,000 (95% UI: 72.50-145.46), respectively. A higher disease burden was observed among Chinese men and individuals aged 70 years or older. Compared to the current trend, a combined scenario involving improvements in environmental factors, behavioral and metabolic health, child nutrition, and vaccination resulted in a greater reduction in the disease burden caused by asthma. CONCLUSION Addressing modifiable risk factors is essential for further reducing the asthma-related disease burden.
Humans ; Asthma/mortality* ; China/epidemiology* ; Male ; Female ; Adult ; Middle Aged ; Aged ; Child ; Adolescent ; Global Burden of Disease/trends* ; Child, Preschool ; Young Adult ; Infant ; Cost of Illness ; Disability-Adjusted Life Years ; Prevalence ; Incidence ; Infant, Newborn ; Aged, 80 and over ; Risk Factors

OBJECTIVES: This study aimed to investigate the impact of foam macrophages (FMs) on the intracellular survival of Mycobacterium tuberculosis (MTB) and identify the molecular mechanisms influencing MTB survival. METHODS: An in vitro FM model was established using oleic acid induction. Transcriptomic and metabolomic analyses were conducted to identify the key molecular pathways involved in FM-mediated MTB survival. RESULTS: Induced FMs effectively restricted MTB survival. Transcriptomic and metabolomic profiling revealed distinct changes in gene and metabolite expression in FMs during MTB infection compared with normal macrophages. Integrated analyses identified significant alterations in the cyclic adenosine monophosphate (cAMP) signaling pathway, indicating that its activation contributes to the FM-mediated restriction of MTB survival. CONCLUSIONS FMs inhibit MTB survival. The cAMP signaling pathway is a key contributor. These findings enhance the understanding of the role of FMs in tuberculosis progression, suggest potential targets for host-directed therapies, and offer new directions for developing diagnostic and therapeutic strategies against tuberculosis.
Mycobacterium tuberculosis/physiology* ; Transcriptome ; Metabolomics ; Foam Cells/microbiology* ; Humans ; Metabolome ; Tuberculosis/microbiology* ; Gene Expression Profiling

Objective To explore the clinical characteristics and influencing factors in type 2 diabetes mellitus(T2DM)patients with metabolic-associated fatty liver disease(MAFLD)who are at moderate-to-high risk of metabolic-associated fatty liver fibrosis.Methods A retrospective analysis was conducted on the clinical data of 495 T2DM patients with MAFLD who were treated in the Department of Endocrinology,the Seventh People's Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,from August 2022 to May 2024.According to the fibrosis-4(FIB-4)index,the patients were divided into two groups:low risk group for metabolic-associated fatty liver fibrosis(n=311)and moderate-to-high risk group for metabolic-associated fatty liver fibrosis(n=184).Differences in clinical characteristics and laboratory test results between the two groups were compared.Univariate and multivariate binary logistic regression analyses were used to screen the influencing factors of moderate-to-high risk of metabolic-associated fatty liver fibrosis in T2DM patients with MAFLD.Receiver operating characteristic(ROC)curves and area under the curve(AUC)were employed to evaluate the predictive value of these factors for moderate-to-high risk of metabolic-associated fatty liver fibrosis in T2DM patients with MAFLD.Results Compared with low risk group,moderate-to-high risk group had significantly higher age,proportions of patients with a history of hypertension and coronary heart disease,as well as higher levels of aspartate aminotransferase(AST),blood urea nitrogen(BUN),and creatinine(Cr)(P<0.05).In contrast,moderate-to-high group had a lower proportion of male patients,and lower levels of platelet count(PLT),total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),glycated hemoglobin(HbA1c),free triiodothyronine(FT3),free thyroxine(FT4),and thyroid feedback quantile-based index(TFQI)(P<0.05).Univariate binary logistic regression analysis showed that male(P=0.020),HbA1c(P=0.014),BUN(P<0.001),Cr(P<0.001),TC(P=0.001),LDL-C(P<0.001),FT3(P<0.001),FT4(P<0.001),and TFQI(P=0.039)were influencing factors for moderate-to-high risk of metabolic-associated fatty liver fibrosis in T2DM patients with MAFLD.Multivariate binary logistic regression analysis revealed that BUN(OR=1.165,95%CI 1.006-1.348,P=0.042)and Cr(OR=1.020,95%CI 1.005-1.036,P=0.008)were independent risk factors for moderate-to-high risk of metabolic-associated fatty liver fibrosis in T2DM patients with MAFLD,while male(OR=0.574,95%CI 0.339-0.972,P=0.039),LDL-C(OR=0.659,95%CI 0.483-0.898,P=0.008),FT3(OR=0.590,95%CI 0.404-0.864,P=0.007),and FT4(OR=0.863,95%CI 0.762-0.977,P=0.020)were independent protective factors.ROC curve analysis showed that the AUC of the combined 6 influencing factors for predicting moderate-to-high risk of metabolic-associated fatty liver fibrosis in T2DM patients with MAFLD was 0.728(95%CI 0.682-0.774),with a sensitivity of 0.620 and a specificity of 0.759.Conclusions Gender,BUN,Cr,LDL-C,FT3,and FT4 are independent influencing factors for moderate-to-high risk of metabolic-associated fatty liver fibrosis in T2DM patients with MAFLD.Monitoring and early intervention for the above abnormal biochemical indices are beneficial in delaying the occurrence and development of liver fibrosis in T2DM patients with MAFLD.

Objective To investigate the mechanism of hippocampal neuronal plasticity of newborn neurons in the hippocampus by which exercise improves the fear and anxiety symptoms of post-traumatic stress disorder(PTSD).Methods Totally 40 C57BL/6J male mice were randomly divided into by control group(Ctrl)and PTSD group,the PTSD group was divided into a no-exercise group(PTSD),a low-intensity exercise group(L)and a high-intensity exercise group(H).The PTSD model mice were constructed by combining conditioned plantar-foot shock(CF)and single-session sustained stress(SPS).After the exercise intervention,the fear and anxiety levels of the mice were assessed using the conditioned fear test and the elevated cross maze test;Subsequently,the densities of the newborn mature neurons in dentate gyrus(DG)of hippocampus were detected by immunofluorescent double-labelling staining,and the newborn neuron morphology was marked by injecting retrovirus pRetro-U6-EF1-EGFP-3xFLAG-WPRE in DG of hippocampus to observe its morphology.The morphology of the newborn neurons was labelled to observe their dendritic length and the number of branch points;Meanwhile,the concentration level of adiponctin(APN)in the hippocampal area was determined by ELISA.Results The result showed that both high and low-intensity exercise interventions significantly reduced the freezing time of PTSD mice in the conditioned fear test,and in the elevated cross maze experiment,the residence time and the number of entries in the open arm of the mice in the H group increased significantly compared with those in the PTSD group,while the residence time and the number of entries in the closed arm were significantly reduced.In addition,both high and low-intensity exercise interventions significantly increased the surface density and dendritic length of newborn mature neurons in the hippocampal DG region of PTSD mice,and high-intensity exercise significantly increased the number of dendritic branching points,and the density of newborn mature neurons in the H group was more significantly increased compared with that in the L group.At the same time,the hippocampal APN concentration increased significantly in both L and H groups compared with the PTSD group,and it was more significant in the H group.Conclusion Exercises have an ameliorative effect on anxiety and fear symptoms in PTSD mice,and at the same time,it can increase hippocampal neuroplasticity and adiponctin secretion in PTSD mice,suggesting that the improvement of fear and anxiety symptoms in PTSD by exercise may be related to the increase of hippocampal neuroplasticity and APN secretion,and the improvement effect is better with high-intensity exercise.

Objective To elucidate the functional role and underlying mechanisms of the ribosome biogenesis factor BMS1 in neuroblastoma(NB)cellular proliferation.Methods We utilized the R2 genomics analysis and visualization platform to analyze the correlation between BMS1 expression levels and clinical characteristics of NB children.The BMS1 mRNA level in three human neuroblastoma cells SK-N-BE(2),BE(2)-C,IMR-32 and two normal cells hTERT RPE-1,IMR-90 was detected by real-time quantitative polymerase chain reaction(RT-qPCR).Two distinct small interfering RNA(siRNA)sequences were used to target BMS1 mRNA in NB cells SK-N-BE(2)and BE(2)-C,with normal cells hTERT RPE-1 serving as controls.We used RT-qPCR to quantify the mRNA levels of BMS1 and two key neuroblastoma-associated molecules(MYCN and p53).After transfection with siRNA,cellular proliferation was detected by various experimental approaches:crystal violet staining,real-time cell analysis(RTCA),colony-forming unit assay and immunofluorescence.Results By analyzing two independent neuroblastoma clinical cohorts(GSE85047/NRC-283 and Westermann-144 datasets),it was found that the BMS1 mRNA level in MYCN-amplified NB was significantly higher than that in MYCN-non-amplified NB(P<0.05).Furthermore,the overall survival rate of NB children in the BMS1 high-expression group was decreased(P<0.05).Consistent with these clinical observations,the BMS1 mRNA level in NB cells SK-N-BE(2),BE(2)-C and IMR-32 was significantly higher than that in normal cells hTERT RPE-1,IMR-90(P<0.05).The targeted transient knockdown of BMS1 in NB cell lines SK-N-BE(2)and BE(2)-C resulted in decreased intracellular MYCN mRNA expression levels(P<0.05),significantly reduced cell proliferation capacity and colony-forming ability(P<0.05).Immunofluorescence revealed that the expression of Ki-67,a proliferation marker,was decreased(P<0.05).At the molecular level,RT-qPCR showed that the p53 mRNA level was significantly elevated in the BMS1-knockdown groups(si BMS1-1#and si BMS1-2#)compared with the control group(P<0.05).However,transient knockdown of BMS1 had no significant impact on the proliferative capacity of normal cells hTERT RPE-1.Conclusion BMS1 expression was up-regulated in MYCN-amplified NB and negatively correlated with the prognosis of the NB children.Mechanistically,interfering with BMS1 expression may transcriptionally activate p53 in NB cells,thereby inhibiting their proliferative ability,while having minimal impact on normal cells growth kinetics.These findings suggest that BMS1 serves as an important proliferation driver in NB and is expected to be a promising therapeutic target for NB children,particularly MYCN-amplified pediatric patients.

AIM To establish a rapid quantitative analysis model for saponins in Paris polyphylla var.yunnanensis(PPY)by near infrared spectroscopy.METHODS The contents of polyphyllins Ⅰ,Ⅱ,Ⅶ and there total content in PPY were determined by HPLC,while spectral data within the range of 10 000 to 4 000 cm-1 were collected.A quantitative analysis model was established by combining these data with partial least squares regression(PLSR).Multivariate scatter correction(MSC)and vector normalization(SNV)were applied prior to further preprocessing the spectra with original,first-order derivative(1stD),or second-order derivative(2ndD)treatments.Lastly,the model was optimized through non-smoothing(NS),Norris Derivative filtering(Nd),and Savitzky-Golay filtering(S-G)method.Model stability was evaluated based on correlation coefficients and variance.The predicted contents of each saponin component in the validation set samples were calculated.RESULTS The contents of polyphyllins Ⅰ,Ⅱ,Ⅶ were 0.42-17.98,0.46-10.44,0.23-3.86 mg/g,respectively.The total content ranged from 2.91 to 22.1 mg/g.The optimal parameters of three saponins were achieved when selecting the MSC+2ndD+S-G pretreatment method.The corresponding ratio of line segment length to segment gap was 13∶5,15∶5,11∶5,with correlation coefficients of 0.982,0.930,0.958,respectively.The root mean square errors of calibration(RMSEC)were 0.702,0.797,0.238,and the root mean square errors of prediction(RMSEP)were 1.120,0.835,0.304,respectively.The optimal parameters for the total content were obtained when selecting the MSC+2ndD+NS pretreatment method,with a correlation coefficient of 0.970,a RMSEC of 1.090,and a RMSEP of 1.740.CONCLUSION This accurate and rapid method can be used for detection of saponin contents in P.Polyphylla.

Radiation prevention and treatment drugs are a rapidly developing field.Radiation prevention and treatment drugs can be roughly divided into four categories:chemical synthetic drugs,biological products,natural plant extracts and traditional Chinese medicine compounds,which are widely used in medical,scientific research and other fields.This paper reviews the classification of radiation prevention and treatment drugs,which can be roughly divided into four categories:chemical synthetic drugs,biological products,natural plant extracts and traditional Chinese medicine compounds.At the same time,its mechanism of action and clinical application are elaborated in detail,and the risk assessment is carried out from the aspects of effectiveness,safety and drug interaction.Finally,the risk reduction strategies are summarized from the aspects of clinical medication specification and monitoring,continuous drug safety research,improvement of emergency reserve and support capacity and construction of full-cycle regulatory system,so as to provide reference for the rational application and further research of radiation prevention and treatment drugs.