Objective To screen metabolic core genes in colon cancer based on machine learning algorithms and analyze their functional mechanisms.Methods Data were obtained from The Cancer Genome Atlas(TCGA)database and the Gene Expression Omnibus(GEO)database.The TCGA co-hort included 375 tumor samples and 32 adjacent normal tissue samples,while the GSE39582 cohort comprised 419 tumor samples.Univariate Cox regression analysis combined with random forest,sup-port vector machine recursive feature elimination(SVM-RFE),and least absolute shrinkage and selec-tion operator(LASSO)regression algorithms were employed to screen for metabolic core genes.Re-ceiver operating characteristic(ROC)curves were plotted,and the area under the curve(AUC)was used to evaluate the predictive efficacy of the core genes.Real-time fluorescent quantitative polymerase chain reaction(qRT-PCR)and immunohistochemistry(IHC)methods were adopted to detect the ex-pression of the core genes.The core genes were knocked down to explore their roles in colon cancer.Results Three core genes,namely CPT2,SCP2 and NR3C2,were screened based on machine learning algorithms.According to the comparison results of the AUCs of the ROC curves,NR3C2 exhibited the best predictive efficacy.qRT-PCR detection results showed that NR3C2 mRNA was lowly ex-pressed in colon cancer cell lines;IHC detection results revealed that NR3C2 was lowly expressed in colon cancer tissues.Knocking down NR3C2 significantly promoted the proliferation and migration of colon cancer cells.Conclusion NR3C2 is identified as a core metabolic inhibitory gene in colon cancer by cross-applying three machine learning algorithms,which may provide a new strategy for metabolic targeted therapy.

Objective To investigate the expression levels of class Ⅰ histone deacetylases(HDAC)in the serum of patients with newly diagnosed psoriatic arthritis(PsA)and screen out serological indicators that are of significance for early diagnosis and assessment of disease activity.Methods A total of 49 PsA patients newly diagnosed in Shanxi Provincial People's Hospital from August 2022 to February 2024 and 30 healthy individuals(control group)were enrolled in this study.Demographic data were collected,and disease severity was assessed.Serum samples were collected,and the expression levels of class Ⅰ HDAC(HDAC1,HDAC2,HDAC3,and HDAC8)in the serum of each group were determined by ELISA.The correlations between the expression levels of class Ⅰ HDAC and clinical assessment indicators in each group were evaluated.Multivariate Logistic regression was adopted to analyze the risk factors affecting the disease activity of PsA patients.The receiver operating characteristic curve was used to evaluate the diagnostic efficacy of the risk factors affecting the disease activity of PsA patients.Results Compared with the control group,PsA patients showed up-regulated expression levels of HDAC1(P=0.003),HDAC2(P=0.010),HDAC3(P=0.003),and HDAC8(P=0.018)in the serum.The serum HDAC1 level of PsA patients was positively correlated with erythrocyte sedimentation rate(r=0.344,P=0.028).The serum HDAC2 level was positively correlated with the overall assessment of disease activity(r=0.468,P=0.001),the disease activity index of arthritis(r=0.401,P=0.007),the number of swollen joints(r=0.308,P=0.042),hospital anxiety and depression scale(HADS)score of anxiety(r=0.360,P=0.018),and HADS score of depression(r=0.302,P=0.047).The serum HDAC3 level was correlated with erythrocyte sedimentation rate(r=0.542,P<0.001),C-reactive protein(CRP)level(r=0.440,P<0.001),HADS score of anxiety(r=0.420,P=0.005),interleukin-6 level(r=0.397,P=0.004),the overall assessment of disease activity(r=0.318,P=0.036),and the course of psoriatic arthritis(r=0.330,P=0.028).The serum HDAC8 level was positively correlated with HADS score of anxiety(r=0.477,P=0.008)and erythrocyte sedimentation rate(r=0.385,P=0.039).Compared with the patients with low disease activity,those with moderate to high disease activity presented up-regulated expression of HDAC3(P=0.041).HDAC2(P=0.028)and CRP(P=0.034)were risk factors for moderate to high disease activity in PsA patients.HDAC2(area under the curve=0.802,P=0.003)and CRP(area under the curve=0.718,P=0.033)had diagnostic value for the progression of PsA.Conclusions The expression levels of class Ⅰ HDAC in the serum of patients with newly diagnosed PsA were significantly different.The serum levels of HDAC2 and CRP are expected to become serological indicators for the early diagnosis and disease activity assessment of PsA.
Humans ; Histone Deacetylases/blood* ; Arthritis, Psoriatic/diagnosis* ; Male ; Female ; Histone Deacetylase 1/blood* ; Histone Deacetylase 2/blood* ; Adult ; Middle Aged ; Clinical Relevance ; Repressor Proteins

Objective To explore CT manifestations of perivascular epithelioid cell tumor(PEComa)of liver and kidney.Methods Totally 18 hepatic PEComa and 5 renal PEComa confirmed by surgical pathology were retrospectively enrolled,and the preoperative CT manifestations were explored.Results Single lesion of liver or kidney was found in all 23 cases,and the main CT manifestations included low or slightly low density lesion(23/23,100％),with irregular morphology(16/23,69.57％),clear boundaries(17/23,73.91％),non-envelope(21/23,91.30％)and enhancement after administration of contrast agents(21/23,91.30％).Among 18 cases of liver PEComa,most lesions(13/18,72.22％)presented as uniform density,while some(5/18,27.88％)presented as non-uniform density lesions often contained with fat components(5/5,100％)and thickened blood vessels(4/5,80.00％)but rare hemorrhagic necrosis(1/5,20.00％)nor calcification(0/5,0).Fast in and fast out of contrast agents were observed in 16(16/18,88.89％)lesions.Uneven density and internal fat components were found in all 5(5/5,100％)renal PEComa,which rarely with hemorrhagic necrosis(1/5,20.00％),blood vessels orientation(1/5,20.00％)and calcification(0/5,0).After enhancement,fast in and fast out,progressive enhancement and non-enhancement was observed in 2(2/5,40.00％),1(1/5,20.00％)and 2(2/5,40.00％)cases,respectively.Conclusion CT manifestations of PEComa in liver and kidney had certain characteristics.

Objective To explore the mechanism of matrine in the treatment of uveal melanoma by network pharmacology,and the related results were verified by molecular docking and cell experiments.Methods The potential targets of matrine were obtained from Swiss Target Prediction,SuperPred and TCMSP databases.The targets related to uveal melanoma were obtained from GeneCards,OMIM,CTD and DrugBank databases.Protein-protein interaction(PPI)network was established to screen core targets.Gene ontology(GO)enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)signal pathway analysis were carried out for potential targets.The interaction between matrine and core targets was evaluated by molecular docking technique.The effects of different concentrations of matrine(0.25 g/L,0.50 g/L,1.00 g/L,2.00 g/L)on the proliferation of uveal melanoma cells were evaluated based on CCK-8 method.Western blot was used to verify the regulatory effects of different concentrations of matrine(0.25 g/L,0.50 g/L,1.00 g/L,2.00 g/L)on PI3K-Akt signaling pathway.Results A total of 208 potential targets of matrine were identified,and 5 453 targets related to uveal melanoma were obtained.The topological analysis of PPI network revealed 8 core targets,namely interleukin-6(IL-6),tumor necrosis factor(TNF),myelocytomatosis proteins(MYC),signal transducer and activator of transcription 3(STAT3),caspase-3(CASP3),heat shock protein 90AB1(HSP90AB1),mammalian target of rapamycin(mTOR),and matrix metalloproteinase 9(MMP9).GO enrichment analysis showed that biological processes(BP)mainly included inflammatory response,protein phosphorylation and response to exogenous stimuli;cell components(CC)mainly included plasma membrane,cell surface and cytoplasm;molecular function(MF)mainly included the same protein binding,ATP binding and kinase activity.The enrichment analysis of KEGG pathway showed that the effect of matrine was mediated by viral carcinogenesis,cancer pathway,TNF signaling pathway and PI3K-Akt signaling pathway.Molecular docking showed that matrine had good binding ability with the selected core targets.The results of cell experiments showed that matrine at concentrations of 0.50 g/L,1.00 g/L and 2.00 g/L could inhibit the proliferation of MuM2B cells,and the cell survival rate gradually decreased with the increase of concentration.Matrine at concentrations of 0.50 g/L,1.00 g/L and 2.00 g/L could down-regulate the protein expression levels of p-PI3K and p-Akt,and the protein expression levels of p-PI3K and p-Akt gradually decreased with the increase of concentration.Conclusion Matrine acts on tar-gets such as IL-6,TNF,MYC,STAT3,CASP3,HSP90AB1,mTOR,MMP9,and exerts therapeutic effects on uveal melanoma by viral carcinogenesis,cancer pathway,TNF signaling pathway and PI3K-Akt signaling pathway,etc.

OBJECTIVE: To observe the therapeutic effect of electroacupuncture (EA) in improving early enteral nutrition tolerance in patients with acute pancreatitis (AP) under the concept of accelerated rehabilitation, and to explore the related mechanism based on the changes in autonomic nerve characteristics. METHODS: A total of 42 patients with AP were randomized into an observation group (21 cases, 1 case dropped out) and a control group (21 cases, 1 case dropped out). The control group received standard basic treatment for AP. On the basis of the treatment in the control group, EA was applied in the observation group, bilateral Zusanli (ST36), Yixian point (Extra), Tianshu (ST25), Neiguan (PC6) and Zhongwan (CV12) were selected as the main points, and the supplementary points were selected according to syndrome differentiation. Ipsilateral Zusanli (ST36) and Yixian point (Extra) were connected to EA, using discontinuous wave, in frequency of 2 Hz, 30 min a time, once a day for 6 continuous days. The enteral nutrition tolerance score was observed before treatment and after 3 and 5 days of treatment; the visual analogue scale (VAS) score for abdominal pain was observed before treatment and after 3 days of treatment; the time of reaching the feeding goal and hospital stay was recorded; the levels of C-reactive protein (CRP) and amylase were measured before treatment and after 5 days of treatment; the heart rate variability (HRV) indexes (standard deviation of NN intervals [SDNN], average standard deviation of NN intervals [SDANN], root mean square of successive NN interval differences [rMSSD], low frequency [LF] and high frequency [HF], ratio of low frequency to high frequency [LF/HF]) were monitored in the two groups. RESULTS: After 3 and 5 days of treatment, the enteral nutrition tolerance scores were decreased compared with those before treatment in both groups (P<0.01), the reductions in the observation group were larger than those in the control group (P<0.01). After 3 days of treatment, the VAS scores for abdominal pain were decreased compared with those before treatment in both groups (P<0.01), the reduction in the observation group was larger than that in the control group (P<0.01). The time of reaching the feeding goal and hospital stay in the observation group was shorter than that in the control group (P<0.05). After 5 days of treatment, the CRP and amylase levels were decreased compared with those before treatment in both groups (P<0.01), the reduction of CRP level in the observation group was larger than that in the control group (P<0.01). In the observation group, SDNN, SDANN and LF/HF were lower than those in the control group (P<0.05, P<0.01), while rMSSD was higher than that in the control group (P<0.01). SDNN, SDANN and LF/HF were positively correlated with the enteral nutrition tolerance scores after 3 and 5 days of treatment (P<0.05), while rMSSD was negatively correlated with the enteral nutrition tolerance scores after 3 and 5 days of treatment (P<0.01). CONCLUSION Electroacupuncture can improve enteral nutrition tolerance in patients with AP by regulating autonomic nervous function, alleviating the inflammation, promoting accelerated recovery, and reducing the length of hospital stay.
Humans ; Electroacupuncture ; Male ; Female ; Enteral Nutrition ; Middle Aged ; Adult ; Pancreatitis/physiopathology* ; Aged ; Acupuncture Points ; Young Adult ; Acute Disease/therapy* ; Autonomic Pathways/physiopathology*

High-performance liquid chromatography(HPLC) was used to determine the content of three major components in Citri Reticulatae Semen(CRS), including limonin, nomilin, and obacunone. The chromaticity of the CRS sample during salt processing and stir-frying was measured using a color difference meter. Next, the relationship between the color and content of the salt-processed CRS sample was investigated through correlation analysis. By integrating the oil bath technique for processing simulation with HPLC, the changes in the relative content of nomilin and its transformation products were analyzed, with its structural transformation pattern during processing identified. Additionally, RAW264.7 cells were induced with lipopolysaccharides(LPSs) to establish an inflammatory model, and the anti-inflammatory activity of nomilin and its transformation product, namely obacunone was evaluated. The results indicated that as processing progressed, E~*ab and L~* values showed a downward trend; a~* values exhibited a slow increase over a certain period, followed by no significant changes, and b~* values remained stable with no significant changes over a certain period and then started to decrease. The limonin content remained barely unchanged; the nomilin content decreased, and the obacunone increased significantly. The changing trends in content and color parameters during salt-processing and stir-frying were basically consistent. The content of nomilin and obacunone was significantly correlated with the colorimetric values(L~*, a~*, b~*, and E~*ab), while limonin content showed no significant correlation with these values. By analyzing HPLC patterns of nomylin at different heating temperatures and time, it was found that under conditions of 200-250 ℃ for heating of 5-60 min, the content of nomilin significantly decreased, while the obacunone content increased pronouncedly. The in vitro anti-inflammatory activity results indicated that compared to the model group, the group with a high concentration of nomilin and the groups with varying concentrations of obacunone showed significantly reduced release of nitric oxide(NO)(P<0.01). When both were at the same concentration, obacunone showed better performance in inhibiting NO release. In this study, the obvious correlation between the color and content of major components during the processing of CRS samples was identified, and the dynamic patterns of quality change in CRS samples during processing were revealed. Additionally, the study revealed and confirmed the transformation of nomilin into obacunone during processing, with the in vitro anti-inflammatory activity of obacunone significantly greater than that of nomilin. These findings provided a scientific basis for CRS processing optimization, tablet quality control, and its clinical application.
Mice ; Animals ; Drugs, Chinese Herbal/pharmacology* ; RAW 264.7 Cells ; Limonins/chemistry* ; Chromatography, High Pressure Liquid ; Citrus/chemistry* ; Color ; Benzoxepins/chemistry* ; Anti-Inflammatory Agents/chemistry*

Objective To explore the mechanism of matrine in the treatment of uveal melanoma by network pharmacology,and the related results were verified by molecular docking and cell experiments.Methods The potential targets of matrine were obtained from Swiss Target Prediction,SuperPred and TCMSP databases.The targets related to uveal melanoma were obtained from GeneCards,OMIM,CTD and DrugBank databases.Protein-protein interaction(PPI)network was established to screen core targets.Gene ontology(GO)enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)signal pathway analysis were carried out for potential targets.The interaction between matrine and core targets was evaluated by molecular docking technique.The effects of different concentrations of matrine(0.25 g/L,0.50 g/L,1.00 g/L,2.00 g/L)on the proliferation of uveal melanoma cells were evaluated based on CCK-8 method.Western blot was used to verify the regulatory effects of different concentrations of matrine(0.25 g/L,0.50 g/L,1.00 g/L,2.00 g/L)on PI3K-Akt signaling pathway.Results A total of 208 potential targets of matrine were identified,and 5 453 targets related to uveal melanoma were obtained.The topological analysis of PPI network revealed 8 core targets,namely interleukin-6(IL-6),tumor necrosis factor(TNF),myelocytomatosis proteins(MYC),signal transducer and activator of transcription 3(STAT3),caspase-3(CASP3),heat shock protein 90AB1(HSP90AB1),mammalian target of rapamycin(mTOR),and matrix metalloproteinase 9(MMP9).GO enrichment analysis showed that biological processes(BP)mainly included inflammatory response,protein phosphorylation and response to exogenous stimuli;cell components(CC)mainly included plasma membrane,cell surface and cytoplasm;molecular function(MF)mainly included the same protein binding,ATP binding and kinase activity.The enrichment analysis of KEGG pathway showed that the effect of matrine was mediated by viral carcinogenesis,cancer pathway,TNF signaling pathway and PI3K-Akt signaling pathway.Molecular docking showed that matrine had good binding ability with the selected core targets.The results of cell experiments showed that matrine at concentrations of 0.50 g/L,1.00 g/L and 2.00 g/L could inhibit the proliferation of MuM2B cells,and the cell survival rate gradually decreased with the increase of concentration.Matrine at concentrations of 0.50 g/L,1.00 g/L and 2.00 g/L could down-regulate the protein expression levels of p-PI3K and p-Akt,and the protein expression levels of p-PI3K and p-Akt gradually decreased with the increase of concentration.Conclusion Matrine acts on tar-gets such as IL-6,TNF,MYC,STAT3,CASP3,HSP90AB1,mTOR,MMP9,and exerts therapeutic effects on uveal melanoma by viral carcinogenesis,cancer pathway,TNF signaling pathway and PI3K-Akt signaling pathway,etc.

ObjectiveChemotherapy is one of the important therapeutic approaches for cancer treatment. However, the emergence of multidrug resistance and side effects significantly limit its application. To address these challenges, chemotherapy is often combined with other drugs or therapies. Among the 13 human fucosyltransferases (FUTs) identified, FUT8 (alpha-(1,6)-fucosyltransferase) is the only enzyme responsible for core fucosylation. Core fucosylation plays an important role in cancer occurrence, metastasis and chemotherapy resistance, making the suppression of FUT8 a potential strategy for reversing multidrug resistance. This study aims to evaluate the feasibility of combining the small molecule FUT8 inhibitor 2FF (2-deoxy-2-fluoro-L-fucose) with the clinical chemotherapeutic drug doxorubicin (DOX) for treating malignant tumors. MethodsThe human hepatocellular carcinoma cell line HepG2 and mouse colon cancer cell line CT26 cells were treated with 2FF, DOX or their combination and core fucosylation levels were assessed using Lectin blot. HepG2 and CT26 cells were exposed to 50 μmol/L 2FF for 72 h, followed by treatment with a gradient concentration of DOX for 24 h. Cell viability and IC₅₀ values were determined via the CCK-8 assay. Transwell invasion assays were conducted to evaluate the combined effect of 2FF and DOX on the invasion ability of HepG2 cells. Flow cytometry was performed to analyze the impact of 2FF, DOX and their combination on membrane PD-L1 expression of HepG2 cells. To assess the in vivo effect, 6- to 8-week-old female BALB/c mice (20-25 g), were subcutaneously injected with 1×10⁶ CT26 cells into the right axilla (four groups, six mice in each group). After the average tumor volume reached 100 mm³, mice were treated with DOX, 2FF, their combination, or saline (mock group) every other day. DOX was administrated intraperitoneally (2 mg/kg), 2FF intravenously (5 mg/kg), and the combination group, received the both treatment. Tumor size was measured every other day using a vernier caliper. ResultsThis study demonstrated that DOX upregulates the core fucosylation levels in HepG2 and CT26 cells,while 2FF effectively inhibits this DOX-induced effect. Furthermone, 2FF enhanced the sensitivity of HepG2 and CT26 cells to DOX. The combination of 2FF and DOX synergistically inhibited the invasion ability of HepG2 cells, and enhanced the anti-tumor efficacy of CT26 subcutaneous tumor model in BALB/c mice. However the combination treatment led to weight loss in mice. In addition, DOX increased the cell surface PD-L1 expression in HepG2 cells, which was effectively suppressed by 2FF. ConclusionThe FUT8 inhibitor 2FF effectively suppresses DOX-induced upregulation of core fucosylation and PD-L1 levels in tumor cells, and 2FF synergistically enhances the anticancer efficacy of DOX.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

AIM To study the chemical constituents from ethyl acetate fraction of Balanophora harlandii Hook.f.and their tyrosinase inhibitory activity.METHODS Separation and purification were performed using silica gel,MCI,ODS,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The monophenolase inhibitory activity was determined by the tyrosinase-catalyzed oxidation of L-tyrosine.RESULTS Twenty-four compounds were isolated and identified as sesamin(1),methyl caffeate(2),quercetin(3),5,7-dihydroxychromanone(4),methyl 3,4-dihydroxybenzoate(5),esculetin(6),kaempferol(7),naringenin(8),pyrogallic acid(9),pinosylvin(10),methyl propionate(11),caffeic acid(12),saccharinol(13),ferulic acid(14),trans-p-hydroxycinnamic acid(15),cinnamic acid(16),vanillic acid(17),vanillin(18),4-hydroxyacetophenone(19),4-hydroxybenzaldehyde(20),apigenin(21),(-)-isolariciresinol(22),(-)-secoisolariciresinol(23)and meso-2,3-di(3′,4′-methylenedioxybenzyl)butane-1,4-diol(24).The IC50 values of compounds 3,5,7,8,19,and 20 ranged from(0.246 5±0.028 3)to(1.278 2±0.021 3)mmol/L.CONCLUSION Compounds 1-9、11、15、17-21、24 are isolated from this plant for the first time,and 1,6,9,17-19,24 are first isolated from genus Balanophora.Compounds 3、5、7、8、19 and 20 have tyrosinase inhibitory activity.