Obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) are linked to numerous chronic conditions, including cardiovascular disease, atherosclerosis, chronic kidney disease, and type II diabetes. Previous research identified the natural flavonoid diosmin, derived from Chrysanthemum morifolium, as a regulator of glucose metabolism. However, its effects on lipid metabolism and underlying mechanisms remained unexplored. The AMP-activated protein kinase (AMPK) pathway serves a critical function in glucose and lipid metabolism. The relationship between diosmin and the AMPK pathway has not been previously documented. This investigation examined diosmin's capacity to reduce lipid content through AMPK pathway activation in hepatoblastoma cell line G2 (HepG2) and 3T3-L1 cells. The study revealed that diosmin inhibits lipogenesis, indicating its potential as an anti-obesity agent in obese mice. Moreover, diosmin demonstrated effective MASLD alleviation in vivo. These findings suggest that diosmin may represent a promising therapeutic candidate for treating obesity and MASLD.
Diosmin/administration & dosage* ; Animals ; AMP-Activated Protein Kinases/genetics* ; Humans ; Non-alcoholic Fatty Liver Disease/enzymology* ; Mice ; Obesity/enzymology* ; Hep G2 Cells ; Male ; 3T3-L1 Cells ; Mice, Inbred C57BL ; Signal Transduction/drug effects* ; Lipid Metabolism/drug effects* ; Chrysanthemum/chemistry* ; Lipogenesis/drug effects*

Objective:To systematically review the progress in the method development and application of distributed learning in the estimation of epidemiological effect and provide methodological reference for multi-center studies.Methods:We conducted a literature retrieval for English papers published up to December 31, 2023 by using keywords of "health/medical big data" and "distributed/federated learning". After consulting experts, we set criteria of paper inclusion and exclusion and created a framework for data extraction. We collected information about basic study details, including method, application, and evaluation. Two researchers independently screened the papers and extracted information. We used EndNote 20 for the management of literatures and EpiData for the management of data.Results:A total of 3 444 papers were collected, and 29 papers were included in the final analysis. Most of the papers (25, 86.2%) were published in or after 2019, and the papers were mainly from the United States (21/29, 72.4%). For the estimation of epidemiological effects, 22 distributed learning methods had been developed, including methods for logistic regression (8), Cox regression (8), Poisson regression (2), and generalized linear mixed model (GLMM) (4), as well as three platforms for distributed analysis (VLP, Vantage6, AusCAT). The 29 papers described 45 applications, with 20 (44.4%) focusing on the establishment of prediction model and 25 (55.6%) on association analysis. Importantly, except for GLMM, current distributed learning methods can estimate effects with little bias in 1-3 rounds of communication. These methods show less bias compared with meta-analysis, especially in the address of data heterogeneity and rare outcomes. However, less studies examined how differences in data structure and sparse data affect results, an area that requires further research.Conclusion:While distributed learning shows promise in epidemiological effect estimation, it is still in early development, requiring further research on data heterogeneity handling and communication efficiency improvement.

Objective:To compare the enrichment effects of ultrafiltration, polyethylene glycol (PEG) precipitation, aluminum salt precipitation, and anionic membrane adsorption-elution on viruses in drinking water.Methods:Using phage MS2 as the target virus, three different concentrations of drinking water samples were prepared, and the samples were enriched by ultrafiltration 1, ultrafiltration 2, PEG precipitation, aluminum salt precipitation, and anionic membrane adsorption-elution method, respectively. Real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to quantify MS2 nucleic acid in pre and post concentrated samples and the recovery rates of MS2 in samples with high, medium and low concentrations were compared among the five methods.Results:Comparing the MS2 enrichment recovery rates of individual enrichment method in water samples of different concentrations, ultrafiltration method 1, PEG precipitation method, aluminum salt precipitation method, and membrane adsorption-elution method were not affected by the sample concentration, and the differences of the recovery rates for the three concentration water samples among the four methods were not statistically significant ( P>0.05). The MS2 enrichment recovery rates of the five enrichment methods were significantly different in all concentration samples ( P<0.05). The recovery rates of ultrafiltration method 1 were higher in all three concentration samples, followed by aluminum salt precipitation and anionic membrane adsorption-elution, PEG precipitation were higher in high concentration samples, but lower in low and medium concentration samples, and the recovery rates of ultrafiltration method 2 were the lowest in all three concentration samples. Comparing the Ct values of MS2 in the enriched samples by five methods, the Ct values of ultrafiltration method 1 were the smallest in the three concentration water samples. There was no statistically significant difference in MS2 Ct values among the five enrichment methods in the medium and high concentration water samples ( P>0.05). In low concentration simulated water samples, only the difference of MS2 Ct value between ultrafiltration method 1 and ultrafiltration method 2 was statistically significant ( Z=16.000, P=0.016). Conclusions:Considering the operation simplicity, operation time and virus recovery rate after enrichment, ultrafiltration was the most effective method for virus enrichment in drinking water.

Objective To explore the mechanism of Yizhu Wendan Decoction in treating eczema through GEO database combined with network pharmacology and experimental verification.Methods TCMSP,BATMAN-TCM and ETCM databases were used to screen the active components of Yizhu Wendan Decoction.Disease target information related to eczema was collected through GEO database.The drug-component-target network and PPI network were constructed by intersections of active component targets and disease targets.GO and KEGG pathway enrichment analyses were performed using DAVID database.CCK-8 method was used to screen out the optimal intervention concentration of freeze-dried powder of Yizhu Wendan Decoction.HaCaT cells were divided into control group,model group,Yizhu Wendan Decoction low concentration group,Yizhu Wendan Decoction high concentration group,si-IL-17RA group,si-IL-17RA+Yizhu Wendan Decoction low concentration group,si-IL-17RA+Yizhu Wendan Decoction high concentration group,Dexamethasone group,si-IL-17RA+Dexamethasone group.Each group was given relevant intervention.The expressions of chemokines and inflammatory factors were detected by qPCR.EdU and Annexin V-FITC/PI double staining were used to detect cell proliferation and apoptosis.Western blot was performed to detect the expressions of proteins related to apoptosis,skin barrier and IL-17 signaling pathway.Results By using databases,180 active components of Yizhu Wendan Decoction were obtained.Combined with GEO database microarrays related to eczema(GSE6012 and GSE57225),8 potential targets of Yizhu Wendan Decoction in the treatment of eczema were obtained.KEGG enrichment pathway mainly involved IL-17 signaling pathway,lipid and atherosclerotic,TNF signaling pathway,fluid shear stress and atherosclerotic,etc.When Yizhu Wendan Decoction freeze-dried powder concentration was 100 μg/mL,cell viability was the strongest.Yizhu Wendan Decoction could significantly inhibit the mRNA expressions of chemokines and inflammatory factors CCL17,CCL22,IL-1β,TNF-α,IL-6,IFN-γ,and increase the mRNA expression of IL-4 in eczema.It promoted the proliferation of HaCaT cells,increased the protein expression of Bcl-2,and reduced the protein expressions of Bad and Cleaved Caspase-3,thus inhibiting HaCaT cells apoptosis;promoted the protein expressions of FLG and LOR,and reduced the expression of MMP9,MMP1,CCL2,FOSL1,IL-17RA proteins in IL-17 signaling pathway.Conclusion Yizhu Wendan Decoction can treat eczema with multiple components,multiple pathways and multiple targets,promote the proliferation of HaCaT cells,inhibit their apoptosis,and restore the skin barrier.Its mechanism may be related to inhibiting the activation of IL-17 signaling pathway.

Aim To explore the potential mechanism of metformin on ATP-binding cassette transport A1(ABCA1)expression.Methods J774A.1 macrophages were treated with metformin and cycloheximide,and ABCA1 expression was determined by Western blot.His-tagged ABCA1 and HA-tagged Ub plasmids were co-transferred into HEK293 cells and stimulated with metformin.Co-immunoprecipitation(Co-IP)was used to test the binding ability of ABCA1 and ubiquitin.Candidate E3 ubiquitin-protein ligases(CE3)of ABCA1 were identified through Co-IP-based pro-teomics.The MIB1 plasmid was constructed and transferred into HEK293 cells,and Western blot was used to determine the effect of metformin and MIB1 on ABCA1 expression.Results Metformin increased the expression of ABCA1 in J774A.1 cells(P<0.01),and inhibited ABCA1 degradation(P<0.05).Metformin disrupted the binding of ABCA1 to ubiquitin(P<0.05).The proteins regulated by metformin in ABCA1 expression were primarily enriched in pathways re-lated to cell development,inflammation and immune defense.Metformin may upregulate ABCA1 protein expression via MIB1(P<0.05).Conclusion Metformin inhibits the degradation of ABCA1 by blocking the ubiquitin-proteasome system(UPS),and MIB1 might act as a candidate E3 ubiquitin-protein ligase(CE3)for ABCA1.

Objective To construct a patient decision aid(PtDA)for exercise training in pa-tients with chronic obstructive pulmonary disease(COPD)and explore its impacts on decision-making quality of patients' exercise regimens.Methods The development of the PtDA for exercise training in COPD patients was accomplished through literature analysis,the Delphi method,and user surveys,followed by an intervention study.A total of 59 inpatients with COPD were included as study sub-jects.The control group received routine care along with general exercise training guidance,while the intervention group received routine care combined with shared decision-making for exercise training based on the PtDA.The decision conflict and decision preparedness levels of patients in both groups were compared before the intervention and on the day of discharge.The exercise self-efficacy of pa-tients was measured before intervention,on the day of discharge,and 1 month and 3 months after dis-charge.Results The intervention group had significantly lower scores for decision conflict and signif-icantly higher scores for decision preparedness and exercise self-efficacy compared with the control group(P＜0.05).Conclusion The PtDA for exercise training can improve decision conflict and de-cision preparedness in COPD patients,enhance their exercise self-efficacy levels,and provide references for healthcare professionals in improving exercise adherence.

Objective To investigate the distribution of traditional Chinese medicine(TCM)syndromes in chronic persistent immunoglobulin A nephropathy(IgAN)and to explore the relationship between TCM syndromes and prognosis based on real-world research.Methods From January 2018 to January 2024,a total of 80 patients with chronic persistent IgAN who were admitted to Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University were included.The clinical baseline data and prognosis-related information were collected.The main outcome indicators were defined as renal failure events of glomerular filtration rate(eGFR)decreased by＞50%,serum creatinine doubled or end-stage renal disease(ESRD).The distribution of TCM syndromes in chronic persistent IgAN and the relationship between different deficiency syndromes and prognosis were preliminarily discussed.Results(1)Among the 80 patients with chronic persistent IgAN,the syndrome manifestations with an occurrence frequency of more than 30%in descending order were foamy urine(75.00%),fatigue and lassitude(71.25%),waist ache(61.25%),dry mouth(31.25%),lower extremity edema(31.25%),aversion to cold and cold limbs(30.00%),and insomnia(30.00%).(2)The commonly-seen root-deficiency syndrome in patients with chronic persistent IgAN was qi and yin deficiency syndrome,with a total of 28 cases(35.00%).And other root-deficiency syndromes were spleen and kidney yang deficiency syndrome in 22 cases(27.50%),lung and spleen qi deficiency syndrome in 15 cases(18.75%),and liver and kidney yin deficiency syndrome in 15 cases(18.75%).The commonly-seen complicated syndrome was water-damp syndrome,with a total of 17 cases(21.25%).The other complicated syndromes were damp-heat syndrome in 15 cases(18.75%),blood-stasis syndrome in 9 cases(11.25%),phlegm-damp syndrome in 7 cases(8.75%),turbidity-toxin syndrome in 5 cases(6.25%),liver depression syndrome in 3 cases(3.75%),and cold-damp syndrome in 1 case(1.25%).(3)Among the 80 patients with chronic persistent IgAN,21 cases(26.25%)had renal failure events,and their syndrome types were lung and spleen qi deficiency syndrome in 9 cases(60.00%),qi and yin deficiency syndrome in 3 cases(10.71%),liver and kidney yin deficiency syndrome in 3 cases(20.00%),and spleen and kidney yang deficiency syndrome in 6 cases(27.27%).The incidence of renal failure events in patients with lung and spleen qi deficiency syndrome was significantly higher than that in the other three syndrome types,and the chi-square test showed that the difference was statistically significant(P＜0.05).(4)Kaplan-Meier survival analysis showed that the cumulative incidence of 2-year and 5-year endpoint events in patients with lung and spleen qi deficiency syndrome was 23.10%and 46.20%,respectively,and the final incidence was 85.00%.The cumulative incidence of 2-year and 5-year endpoint events in patients with other deficiency syndromes was 4.50%and 19.70%,respectively,and the final incidence was 71.60%.The intergroup comparison(tested by Log-rank)showed that the incidence of renal failure events in patients with lung and spleen qi deficiency syndrome was significantly higher than that in patients with other root-deficiency syndromes,and the difference was statistically significant(P＜0.05).(5)COX proportional hazard regression analysis showed that lung and spleen qi deficiency syndrome(HR=7.755,95%CI 1.631-36.874,P＜0.05)and anemia(HR=8.205,95%CI 1.007-66.857,P＜0.05)were the independent risk factors for renal failure events in patients with chronic persistent IgAN.Conclusion Qi and yin deficiency syndrome is the most common syndrome in the patients with chronic persistent IgAN,and lung and spleen qi deficiency syndrome and anemia are the independent risk factors for renal failure events in IgAN.

Microbial communities such as those residing in the human gut are highly diverse and complex, and many with important implications for health and diseases. The effects and functions of these microbial communities are determined not only by their species compositions and diversities but also by the dynamic intra- and inter-cellular states at the transcriptional level. Powerful and scalable technologies capable of acquiring single-microbe-resolution RNA sequencing information in order to achieve a comprehensive understanding of complex microbial communities together with their hosts are therefore utterly needed. Here we report the development and utilization of a droplet-based smRNA-seq (single-microbe RNA sequencing) method capable of identifying large species varieties in human samples, which we name smRandom-seq2. Together with a triple-module computational pipeline designed for the bacteria and bacteriophage sequencing data by smRandom-seq2 in four human gut samples, we established a single-cell level bacterial transcriptional landscape of human gut microbiome, which included 29,742 single microbes and 329 unique species. Distinct adaptive response states among species in Prevotella and Roseburia genera and intrinsic adaptive strategy heterogeneity in Phascolarctobacterium succinatutens were uncovered. Additionally, we identified hundreds of novel host-phage transcriptional activity associations in the human gut microbiome. Our results indicated that smRandom-seq2 is a high-throughput and high-resolution smRNA-seq technique that is highly adaptable to complex microbial communities in real-world situations and promises new perspectives in the understanding of human microbiomes.
Humans ; Gastrointestinal Microbiome/genetics* ; Bacteriophages/physiology* ; High-Throughput Nucleotide Sequencing ; Sequence Analysis, RNA/methods* ; Bacteria/virology*

OBJECTIVE To study the anatomic characteristics of the anterior ethmoidal canal(AEC)based on 0.1 mm ultra-high resolution CT.METHODS Nine cadavers(18 side orbits)fixed in 10%buffered formalin were enrolled and underwent U-HRCT and MSCT.Divided AEC into horizontal,superior oblique,and inferior oblique segments and observed the displaying rate of each section.Subjective evaluation of display situation was performed by two experienced radiologists independently.The diameter of each AEC segment was measured.RESULTS No significant difference was found in the display rate of the horizontal and superior oblique segments between U-HRCT and MSCT groups(P>0.05),the display rate of inferior oblique segment of U-HRCT group was significantly higher than MSCT group(P<0.05).There was no significant difference in the objective evaluation results between two evaluators and consistency was strong.Subjective scores of each segment of AEC in U-HRCT group were 10.00 points(9.75 points,10.00 points),2.00 points(2.00 points,3.00 points)and 8.00 points(6.00 points,10.00 points),in MSCT group were7.00 points(5.75 points,8.00 points),2.00 points(2.00 points,2.00 points)and 2.00 points(2.00 points,4.00 points).Subjective scores of horizontal and inferior oblique segments of AEC in U-HRCT were higher than MSCT(P<0.05).The anteroposterior diameter of the horizontal section of AEC is(0.92±0.12)mm,the axial diameter is(1.04±0.22)mm.The anteroposterior diameter of the inferior oblique segment is(0.47±0.08)mm,and the transverse diameter is(0.50±0.06)mm.The anteroposterior diameter of the superior oblique segments is(0.66±0.11)mm,and the transverse diameter is(0.72±0.20)mm.CONCLUSION U-HRCT is better to evaluate AEC than MSCT.It could be used to help to study the anatomic characteristics of AEC before surgery to avoid complications.

Aim To explore the potential mechanism of metformin on ATP-binding cassette transport A1(ABCA1)expression.Methods J774A.1 macrophages were treated with metformin and cycloheximide,and ABCA1 expression was determined by Western blot.His-tagged ABCA1 and HA-tagged Ub plasmids were co-transferred into HEK293 cells and stimulated with metformin.Co-immunoprecipitation(Co-IP)was used to test the binding ability of ABCA1 and ubiquitin.Candidate E3 ubiquitin-protein ligases(CE3)of ABCA1 were identified through Co-IP-based pro-teomics.The MIB1 plasmid was constructed and transferred into HEK293 cells,and Western blot was used to determine the effect of metformin and MIB1 on ABCA1 expression.Results Metformin increased the expression of ABCA1 in J774A.1 cells(P<0.01),and inhibited ABCA1 degradation(P<0.05).Metformin disrupted the binding of ABCA1 to ubiquitin(P<0.05).The proteins regulated by metformin in ABCA1 expression were primarily enriched in pathways re-lated to cell development,inflammation and immune defense.Metformin may upregulate ABCA1 protein expression via MIB1(P<0.05).Conclusion Metformin inhibits the degradation of ABCA1 by blocking the ubiquitin-proteasome system(UPS),and MIB1 might act as a candidate E3 ubiquitin-protein ligase(CE3)for ABCA1.