ObjectiveTo establish an ultra-performance liquid fingerprint and multi-components determination method for Naomaili granules. To evaluate the quality of different batches by chemometrics， and the anti-neuroinflammatory effects of water extract and main components of Naomaili granules were tested in vitro. MethodsThe similarity and common peaks of 27 batches of Naomaili granules were evaluated by using Ultra performance liquid chromatography （UPLC） fingerprint detection. Ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） technology was used to determine the content of the index components in Naomaili granules and to evaluate the quality of different batches of Naomaili granules by chemometrics. LPS-induced BV-2 cell inflammation model was used to investigate the anti-neuroinflammatory effects of the water extract and main components of Naomaili granules. ResultsThe similarity of fingerprints of 27 batches of samples was > 0.90. A total of 32 common peaks were calibrated， and 23 of them were identified and assigned. In 27 batches of Naomaili granules， the mass fractions of 14 components that were stachydrine hydrochloride， leonurine hydrochloride， calycosin-7-O-glucoside， calycosin，tanshinoneⅠ， cryptotanshinone， tanshinoneⅡ_A， ginsenoside Rb₁， notoginsenoside R₁， ginsenoside Rg₁， paeoniflorin， albiflorin， lactiflorin， and salvianolic acid B were found to be 2.902-3.498， 0.233-0.343， 0.111-0.301， 0.07-0.152， 0.136-0.228， 0.195-0.390， 0.324-0.482， 1.056-1.435， 0.271-0.397， 1.318-1.649， 3.038-4.059， 2.263-3.455， 0.152-0.232， 2.931-3.991 mg∙g^-1， respectively. Multivariate statistical analysis showed that paeoniflorin， ginsenoside Rg₁， ginsenoside Rb₁ and staphylline hydrochloride were quality difference markers to control the stability of the preparation. The results of bioactive experiment showed that the water extract of Naomaili granules and the eight main components with high content in the prescription had a dose-dependent inhibitory effect on the release of NO in the cell supernatant. Among them， salvianolic acid B and ginsenoside Rb₁ had strong anti-inflammatory activity， with IC₅₀ values of （36.11±0.15） mg∙L^-1 and （27.24±0.54） mg∙L^-1， respectively. ConclusionThe quality evaluation method of Naomaili granules established in this study was accurate and reproducible. Four quality difference markers were screened out， and eight key pharmacodynamic substances of Naomaili granules against neuroinflammation were screened out by in vitro cell experiments.

ObjectiveTo investigate the current situation of mutual recognition for ethical review outcomes in multicenter clinical research across 10 contracting medical institutions in Guangdong Province， analyze existing issues and propose improvement recommendations， thereby promoting the standardized management of mutual recognition for ethical review outcomes in medical institutions. MethodsData from 381 multicenter clinical studies conducted in these 10 medical institutions from January 24 to October 31， 2024， were collected. Text visualization was performed using Python and the WordCloud library， and statistical analyses were conducted with SPSS 25.0. ResultsOf the 381 studies investigated， industry-sponsored clinical trials （ISTs） accounted for 51.71%， while investigator-initiated clinical trials （IITs） constituted 48.29%. The proportions of ethical committees serving as primary reviewers and collaborative reviewers were 33.33% and 66.67%， respectively. The confirmation methods of mutual recognition outcomes were primarily expedited reviews （50.66%） and meeting reviews （49.34%）， and no cases of “direct confirmation” were found. The Chi-square test revealed statistically significant differences in review confirmation methods based on project type （χ²=14.851， P<0.001） and ethics committee role （χ²= 69.435， P<0.001）. The frequency distribution trend of the contingency table showed that IST projects and primary ethics committees preferred to employ meeting review （58.88% and 79.53% respectively， both higher than the average level of 49.34%）， while IIT projects and the collaborative ethics committees more frequently utilized expedited review （60.87% and 65.75% respectively， both higher than the average level of 50.66%）. ConclusionThe confirmation methods of mutual recognition for ethical review outcomes in multicenter clinical research are significantly associated with the role of the ethics committee and the type of project. It is recommended to improve management systems， enhance information construction and personnel training， as well as clarify mutual recognition responsibilities and strengthen supervision. This aims to ensure review quality while improving mutual recognition efficiency， thereby safeguarding the rights and interests of research participants.

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: 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 investigate chronic hepatitis C virus (HCV) infection's effect on gestational liver function, pregnancy and delivery complications, and neonatal development. METHODS: A total of 157 HCV antibody-positive (anti-HCV[+]) and HCV RNA(+) patients (Group C) and 121 anti-HCV(+) and HCV RNA(-) patients (Group B) were included as study participants, while 142 anti-HCV(-) and HCV RNA(-) patients (Group A) were the control group. Data on biochemical indices during pregnancy, pregnancy complications, delivery-related information, and neonatal complications were also collected. RESULTS: Elevated alanine aminotransferase (ALT) rates in Group C during early, middle, and late pregnancy were 59.87%, 43.95%, and 42.04%, respectively-significantly higher than Groups B (26.45%, 15.70%, 10.74%) and A (23.94%, 19.01%, 6.34%) ( P < 0.05). Median ALT levels in Group C were significantly higher than in Groups A and B at all pregnancy stages ( P < 0.05). No significant differences were found in neonatal malformation rates across groups ( P > 0.05). However, neonatal jaundice incidence was significantly greater in Group C (75.16%) compared to Groups A (42.25%) and B (57.02%) ( χ ² = 33.552, P < 0.001). HCV RNA positivity during pregnancy was an independent risk factor for neonatal jaundice ( OR = 2.111, 95% CI 1.242-3.588, P = 0.006). CONCLUSIONS Chronic HCV infection can affect the liver function of pregnant women, but does not increase the pregnancy or delivery complication risks. HCV RNA(+) is an independent risk factor for neonatal jaundice.
Humans ; Female ; Pregnancy ; Adult ; Pregnancy Complications, Infectious/epidemiology* ; Retrospective Studies ; Pregnancy Outcome ; Infant, Newborn ; Viremia/virology* ; Hepatitis C ; Hepacivirus/physiology* ; Hepatitis C, Chronic/virology* ; Young Adult ; Alanine Transaminase/blood*

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Abstract To explore the influence of the occurrence and development of bystander behavior in cyberbullying among adolescents, the paper reviews the factors influencing bystander behavior from the perspective of social ecosystem theory at the individual level, microsystem (family and school factors), peripheral system (contextual factors), macrosystem (cultural factors) and digital environment (media factors). It is pointed out that the future research needs to further explore the internal interaction of micro system, the influence of time system and technological development on bystanders, and the complex interaction between social ecosystems, and design feasible intervention strategies to transform passive bystanders into active interveners.

Objective:To investigate the transcriptional level expression of olfactomedin-like protein 2A (OLFML2A) in peripheral blood of patients with acute leukemia (AL) and its diagnostic and prognostic evaluation value.Methods:A retrospective cohort study was conducted. A total of 34 patients with AL (AL group) admitted to the Second People's Hospital of Lianyungang from January 2019 to March 2023 were selected, including 26 cases of acute myeloid leukemia (AML) (non-acute promyelocytic leukemia) and 8 cases of acute lymphoblastic leukemia (ALL). Another 15 healthy subjects who underwent the physical examination during the same period were selected as the healthy control group. Among 26 patients with AML, 18 were males and 8 were females. The median age [ M (IQR)] was 59 (9) years; 5 cases relapsed. Among 8 patients with ALL, 4 were males and 4 were females. The median age was 48 (12) years; 1 case relapsed. Real-time fluorescence quantitative polymerase chain reaction (qPCR) medthod was used to detect the relative expression level of OLFML2A mRNA in peripheral blood of each group. The relative expression levels of OLFML2A mRNA among the different patients stratified by clinicopathological factors were compared. Taking bone marrow smear cytology or bone marrow biopsy as the gold standard, receiver operating characteristic (ROC) curve was used to analyze the diagnostic effect of the relative expression level of OLFML2A mRNA on AML and ALL. According to the median relative expression level of OLFML2A mRNA in AL patients, the patients were divided into the high expression of OLFML2A mRNA (≥ the median) and the low expression of OLFML2A mRNA (< the median) groups. Progression-free survival (PFS) and overall survival (OS) of both groups were analyzed by using Kaplan-Meier curve. The log-rank test was used for comparison between groups. Results:The median relative expression level of OLFML2A mRNA in AL group was higher than that in the healthy control group [3.53 (8.19) vs. 0.27 (0.23)], and the difference was statistically significant ( Z = 4.38, P < 0.001). The median relative expression level of OLFML2A mRNA in AML group was higher than that in ALL group [4.92, (9.80) vs. 1.60 (4.35)], which were higher than that in the healthy control group; and the differences were statistically significant (all P < 0.05). There were statistically significant differences in the relative expression level of OLFML2A mRNA among AML patients with different prognosis risk stratification, fusion gene positive or not, whether there was chromosome abnormality, and whether the average daily hospitalization cost was < 2 500 yuan (all P < 0.05). There were statistically significant differences in the relative expression level of OLFML2A mRNA among ALL patients with different prognostic risk stratification, whether there was fusion gene and whether there was chromosome abnormality (all P < 0.05). ROC curve analysis showed that the area under the curve for the diagnosis of AML based on the relative expression level of OLFML2A mRNA was 0.936 (95% CI: 0.862-1.000), and the optimal cut-off value was 0.780; the area under the curve for the diagnosis ALL was 0.767 (95% CI: 0.535-0.998), and the optimal cut-off value was 0.558. Kaplan-Meier survival curve analysis showed that the 3-year PSF rate in AL patients with high expression of OLFML2A mRNA (17 cases) and low expression of OLFML2A mRNA was 20.5% and 30.6%, respectively, and PFS in AL patients with low expression of OLFML2A mRNA was superior to those with high expression, and the difference was statistically significant ( χ2 = 4.64, P = 0.031). The 3-year OS rates in AL patients with high and low expression of OLFML2A mRNA was 40.4% and 33.3%, respectively, and there was no statistically significant difference in OS between the 2 groups ( χ2 = 1.55, P = 0.213). Conclusions:The relative expression level of OLFML2A mRNA is high in AL patients, and it is more significant in AML patients. The level of OLFML2A gene has a certain value in the diagnostic and prognostic evaluation of AL.

BACKGROUND:The development of calcium phosphate bone cement is limited due to its poor mechanical properties and weak osteogenic ability.Silicate bioactive glass is highly favored due to its excellent biological activity and osteogenic ability.Simultaneously,fiber structures can enhance the mechanical strength of materials.OBJECTIVE:To investigate the mechanical properties,biocompatibility,and osteogenic effect of silicate bioactive glass fiber composite calcium phosphate bone cement.METHODS:Different mass percentages(0％,10％,and 20％)of silicate bioactive glass fiber were added to the solid phase of calcium phosphate bone cement,mixed with the liquid phase and cured for 48 hours to obtain silicate bioactive glass fiber composite calcium phosphate bone cement.The mechanical properties,setting time,and ion precipitation of the cement were characterized.The three groups of bone cement extracts were co-cultured with MC3T3-E1 cells.The cell compatibility of the materials was evaluated by CCK-8 assay,live/dead staining,and phalloidin staining.After osteogenic induction,the osteogenic induction ability of the materials was evaluated by alkaline phosphatase staining,alizarin red staining,RUNX2 immunofluorescence staining,and RT-PCR.RESULTS AND CONCLUSION:(1)With the increase of silicate bioactive glass fiber content,the compressive strength and flexural strength of bone cement increased,and the setting time was prolonged.When bone cement was immersed in simulated body fluid,the precipitation of silicon ions,calcium ions,and phosphorus ions could be detected.Moreover,with the increase of silicate bioactive glass fiber content,the mass concentration of silicon ions and phosphorus ions released by bone cement increased,and the mass concentration of calcium ions decreased.(2)Live/dead staining and phalloidin staining results exhibited that silicate bioactive glass fiber composite calcium phosphate bone cement had no toxic effect on MC3T3-E1 cells.CCK-8 assay results showed that silicate bioactive glass fiber composite calcium phosphate bone cement could promote the proliferation of MC3T3-E1 cells.(3)With the increase of silicate bioactive glass fiber content in bone cement,the alkaline phosphatase activity and extracellular calcium deposition of MC3T3-E1 cells increased,the expression of RUNX2 protein increased,and the expression of alkaline phosphatase,osteocalcin,osteopontin,and RUNX2 mRNA expression increased.(4)The results indicate that silicate bioactive glass fibers can enhance the mechanical properties and osteogenic induction ability of calcium phosphate bone cement,among which 20％silicate bioactive glass fibers have a more obvious effect.

Objective:To investigate the potential utility of the lymphocyte to monocyte ratio (LMR) and its modified index, albumin-LMR product, as predictive biomarkers for disease activity and presence of lupus nephritis in systemic lupus erythematosus (SLE).Methods:A total of 264 patients with newly diagnosed SLE who were treated at Henan Provincial People′s Hospital between December 2016 and September 2022 were included in this study. Their clinical data were subsequently collected for analysis. Patients were classified into non-active disease group (SLEDAI<5, n=55) and active disease group(SLEDAI≥5, n=209) based on the SLE SLEDAI. The Mann-Whitney U test was employed to compare the differences in clinical parameter levels, LMR and albumin-LMR product between the two groups. Additionally, the active disease group was further stratified into mild(SLEDAI 5~9, n=86), moderate(SLEDAI 10~14, n=96) and severe (SLEDAI≥15, n=27) subgroups to assess differences in LMR and albumin-LMR product. Further more patients were stratified into two groups based on renal involvement: those without lupus nephritis(non-LN) and those with lupus nephritis (LN). For non-parametric comparisons, the Mann-Whitney U test was used for intergroup comparisons between two groups, while the Kruskal-Wallis H test was applied for comparisons among three groups. If the Kruskal-Wallis H test revealed statistically significant differences ( P<0.05), pairwise comparisons were performed using the Mann-Whitney U test, and the significance level was adjusted using the Bonferroni method to account for multiple testing.Correlations between LMR, albumin-LMR product, and disease activity indicators were analyzed using Spearman′s correlation. The diagnostic value of LMR and albumin-LMR product for SLE activity was evaluated using the receiver operating characteristic (ROC) curves. Results:Both LMR and albumin-LMR product were significantly lower in active disease group compared to the non-active group {LMR:3.56 (2.15, 5.00) vs. 5.68 (3.89, 7.00); albumin-LMR product [93.21 (59.50, 143.98)g/L] vs. [187.89 (137.67, 260.90)]g/L, Z=-5.68, -7.05, P<0.001 for all}. Further subgroup analysis revealed that LMR and albumin-LMR product levels in severe, moderate, and mild active disease were also significantly decreased compared to the non-active disease group {LMR:3.83(1.78, 5.09)、3.09(2.06, 4.90)、3.65(2.45, 5.03) vs. 5.68(3.89, 7.00); albumin-LMR product: [95.69(66.57, 121.61)]g/L、[79.82(49.02, 126.91)]g/L、[104.73(69.21, 169.01)]g/L vs. [187.89(137.67, 260.90)]g/L, H=34.27, 58.29, P<0.001 for all}. A significant disparity in the levels of LMR and albumin-LMR product was detected between the non-LN and LN, with statistical significance ( Z=-3.44, P=0.001 and Z=-7.06, P<0.001). Correlation analysis indicated that LMR negatively correlated with SLEDAI( r=-0.31), urea( r=-0.29), creatinine ( r=-0.28) and 24-hour urinary protein level ( r=-0.27), all P<0.001, with no significant correlation to complement C3 or C4. Albumin-LMR product showed stronger negative correlations with SLEDAI ( r=-0.44), urea ( r=-0.40), creatinine ( r=-0.37), and 24-hour urinary protein ( r=-0.55), all P<0.001, and a positive correlation with complement C3 ( r=0.18, P=0.004). The areas under the ROC curves for LMR and LMR combined with complement C3 were 0.749 and 0.795, respectively, while for albumin-LMR product and its combination with complement C3, they were 0.809 and 0.833, indicating superior diagnostic efficacy for the modified albumin-LMR product. Conclusion:LMR and albumin-LMR product levels are significantly associated with SLE disease activity and may serve as potential biomarkers for assessing SLE activity and the degree of lupus nephritis.