ObjectiveTo investigate the therapeutic mechanism of Danhe granules in treating mixed hyperlipidemia based on network pharmacology， as well as animal and cell experiments. MethodsThe active compounds and targets of Danhe granules were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the Encyclopedia of Traditional Chinese Medicine （ETCM）. Related targets for mixed hyperlipidemia were obtained from the GeneCards database. The intersecting targets were subjected to Gene Ontology （GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. A high-fat model was established in human hepatocellular carcinoma cells （HepG2） induced by palmitic acid （PA）， followed by intervention with Danhe granules to assess intracellular lipid accumulation and oxidative stress levels. A mixed hyperlipidemia rat model was also established and divided into low-， medium-， and high-dose Danhe granules groups （1.134， 2.268， and 4.536 g·kg^-1， respectively）， as well as a positive control group treated with pravastatin sodium （4.020 mg·kg^-1）. After eight weeks of intervention， serum lipid levels， inflammatory factors， oxidative stress indices， and the expression of key hepatic lipid metabolism-related proteins were determined. ResultsNetwork pharmacology identified 93 intersecting targets between Danhe granules and mixed hyperlipidemia， with peroxisome proliferator-activated receptor gamma （PPARG）， peroxisome proliferator-activated receptor alpha （PPARA）， tumor necrosis factor （TNF）， interleukin-6 （IL-6）， and IL-1B among the key nodes. The PPAR signaling pathway， AGE/RAGE signaling pathway， lipid metabolism， atherosclerosis and non-alcoholic fatty liver disease （NAFLD） were among the most significantly enriched pathways. Cellular experiments demonstrated that Danhe granules significantly reduced reactive oxygen species （ROS） and malondialdehyde （MDA） levels while increasing catalase （CAT） activity （P<0.05）， thereby alleviating intracellular lipid accumulation and triglyceride （TG） content in HepG2. In animal experiments， Danhe granules markedly decreased serum total cholesterol （TC）， TG， and low-density lipoprotein cholesterol （LDL-C） levels （P<0.05）， reduced hepatic MDA levels， and elevated superoxide dismutase （SOD） and CAT levels. Histological analysis showed alleviation of hepatic steatosis， upregulation of hepatic PPARA and lipoprotein lipase （LPL） expressions， and downregulation of sterol regulatory element-binding protein 1 （SREBP1） expression （P<0.05， P<0.01）. ConclusionDanhe granules improve lipid metabolism disorders in mixed hyperlipidemia by reducing MDA levels， enhancing SOD and CAT activities， scavenging excessive ROS， inhibiting oxidative stress， and mitigating liver injury. The underlying mechanism may involve the upregulation of PPARA and LPL and the suppression of SREBP1 expression.

ObjectiveTo investigate the therapeutic mechanism of Danhe granules in treating mixed hyperlipidemia based on network pharmacology， as well as animal and cell experiments. MethodsThe active compounds and targets of Danhe granules were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the Encyclopedia of Traditional Chinese Medicine （ETCM）. Related targets for mixed hyperlipidemia were obtained from the GeneCards database. The intersecting targets were subjected to Gene Ontology （GO） functional annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. A high-fat model was established in human hepatocellular carcinoma cells （HepG2） induced by palmitic acid （PA）， followed by intervention with Danhe granules to assess intracellular lipid accumulation and oxidative stress levels. A mixed hyperlipidemia rat model was also established and divided into low-， medium-， and high-dose Danhe granules groups （1.134， 2.268， and 4.536 g·kg^-1， respectively）， as well as a positive control group treated with pravastatin sodium （4.020 mg·kg^-1）. After eight weeks of intervention， serum lipid levels， inflammatory factors， oxidative stress indices， and the expression of key hepatic lipid metabolism-related proteins were determined. ResultsNetwork pharmacology identified 93 intersecting targets between Danhe granules and mixed hyperlipidemia， with peroxisome proliferator-activated receptor gamma （PPARG）， peroxisome proliferator-activated receptor alpha （PPARA）， tumor necrosis factor （TNF）， interleukin-6 （IL-6）， and IL-1B among the key nodes. The PPAR signaling pathway， AGE/RAGE signaling pathway， lipid metabolism， atherosclerosis and non-alcoholic fatty liver disease （NAFLD） were among the most significantly enriched pathways. Cellular experiments demonstrated that Danhe granules significantly reduced reactive oxygen species （ROS） and malondialdehyde （MDA） levels while increasing catalase （CAT） activity （P<0.05）， thereby alleviating intracellular lipid accumulation and triglyceride （TG） content in HepG2. In animal experiments， Danhe granules markedly decreased serum total cholesterol （TC）， TG， and low-density lipoprotein cholesterol （LDL-C） levels （P<0.05）， reduced hepatic MDA levels， and elevated superoxide dismutase （SOD） and CAT levels. Histological analysis showed alleviation of hepatic steatosis， upregulation of hepatic PPARA and lipoprotein lipase （LPL） expressions， and downregulation of sterol regulatory element-binding protein 1 （SREBP1） expression （P<0.05， P<0.01）. ConclusionDanhe granules improve lipid metabolism disorders in mixed hyperlipidemia by reducing MDA levels， enhancing SOD and CAT activities， scavenging excessive ROS， inhibiting oxidative stress， and mitigating liver injury. The underlying mechanism may involve the upregulation of PPARA and LPL and the suppression of SREBP1 expression.

ObjectiveTo investigate the mechanism by which Jianpi Xiao'ai prescription （JPXAP） inhibits colorectal cancer progression by regulating the inducible nitric oxide synthase-arginase 1 （iNOS-ARG1） metabolic axis and inducing mitochondrial reactive oxygen species （mito-ROS）-mediated mitochondrial structural and functional impairment. MethodsAn arginine metabolism disorder model of human colorectal cancer HCT116 cells was established by combined treatment with recombinant human interferon-γ （IFN-γ， 10 μg·L^-1） and N（ω）-hydroxy-L-arginine （Nor-NOHA， 200 μmol·L^-1） for 24 h， followed by intervention with 5%， 10%， or 20% JPXAP-containing serum. Cell proliferation was assessed using cell counting kit-8 （CCK-8）， 5-ethynyl-2′-deoxyuridine （EdU） staining， and colony formation assays. Cell invasion and migration were evaluated using Transwell chamber and wound healing assays. Mitochondrial membrane potential （MMP） and ROS levels were assessed by JC-1 and MitoSOX staining， respectively. Mitochondrial ultrastructure was observed by transmission electron microscopy （TEM）. The expression of iNOS， ARG1， and mitochondrial dynamics-related proteins， including mitofusin 2 （MFN2） and dynamin-related protein 1 （DRP1）， was analyzed by Western blot and immunofluorescence. The levels of L-arginine， citrulline， and urea were determined by colorimetric methods and enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the blank group， the model group exhibited significantly upregulated iNOS expression， downregulated ARG1 expression， a decreased ARG1/iNOS ratio， reduced L-arginine and urea levels， and increased citrulline levels （P<0.05）. Meanwhile， mito-ROS accumulation was significantly increased， the JC-1 red/green fluorescence ratio was decreased， and mitochondria showed swelling and cristae disruption， indicating that metabolic disorder induced mitochondrial injury. Compared with the model group， all JPXAP-treated groups further decreased the ARG1/iNOS ratio， enhanced nitric oxide （NO） and reactive nitrogen species accumulation， further reduced L-arginine and urea levels， and increased citrulline levels （P<0.01）. EdU-positive rate， colony formation rate， wound healing rate， and Transwell invasion number all decreased significantly with increasing serum concentration （P<0.01）. Mito-ROS levels were further elevated， and the JC-1 red/green ratio further decreased. TEM revealed aggravated mitochondrial swelling and vacuolization. MFN2 expression was downregulated and DRP1 expression was upregulated （P<0.01），in a dose-dependent manner. ConclusionJPXAP further activates NO-mediated oxidative/nitrosative stress under arginine metabolism imbalance， inducing mito-ROS accumulation， MMP collapse， and mitochondrial dynamics imbalance， thereby inhibiting colorectal cancer cell proliferation and migration. These findings reveal an antitumor mechanism of JPXAP based on coordinated targeting of the "metabolism-mitochondria" axis.

Sustained inflammatory responses are closely related to various severe diseases,and inhibiting the excessive activation of inflammasomes and pyroptosis has significant implications for clinical treatment.Natural products have garnered considerable concern for the treatment of inflammation.Huanglian-Wumei decoction(HLWMD)is a classic prescription used for treating inflammatory diseases,but the necessity of their combination and the exact underlying anti-inflammatory mechanism have not yet been elucidated.Inspired by the supramolecular self-assembly strategy and natural drug compatibility theory,we successfully obtained berberine(BBR)-chlorogenic acid(CGA)supramolecular(BCS),which is an herbal pair from HLWMD.Using a series of characterization methods,we confirmed the self-assembly mechanism of BCS.BBR and CGA were self-assembled and stacked into amphiphilic spherical supra-molecules in a 2:1 molar ratio,driven by electrostatic interactions,hydrophobic interactions,and π-πstacking;the hydrophilic fragments of CGA were outside,and the hydrophobic fragments of BBR were inside.This stacking pattern significantly improved the anti-inflammatory performance of BCS compared with that of single free molecules.Compared with free molecules,BCS significantly attenuated the release of multiple inflammatory mediators and lipopolysaccharide(LPS)-induced pyroptosis.Its anti-inflammatory mechanism is closely related to the inhibition of intracellular nuclear factor-kappaB(NF-κB)p65 phosphorylation and the noncanonical pyroptosis signalling pathway mediated by caspase-11.

Objective:To evaluate the efficacy and safety of the Chi-BEAM regimen (chidamide combined with carmustine, etoposide, cytarabine, and melphalan) followed by autologous hematopoietic stem cell transplantation (ASCT) in patients with high-risk or relapsed/refractory lymphoma.Methods:This retrospective case series included 78 patients with newly treated high-risk or relapsed/refractory lymphoma who underwent ASCT with the Chi-BEAM conditioning regimen in the Department of Hematology, the First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital), from June 2021 to May 2024. Descriptive statistics were employed to evaluate clinical characteristics, efficacy, and adverse events. The Kaplan-Meier method was applied to calculate cumulative progression-free survival (PFS) and overall survival (OS) rates.Results:The median age of the 78 evaluable patients was 47 years (range 16-68), with 8 patients (10.3%) aged ≥60 years. At the first post-transplant assessment (3 months), the objective response rate was 94.9% (74/78). The median follow-up was 20.1 months (range 2.9-44.9). The median PFS time was 20.1 months (range 1.6-45.1), with a 2-year cumulative PFS rate of 81.8%. The median OS time was 20.6 months (range 3.1-45.1), with a cumulative 2-year OS rate of 93.2%. The regimen was well-tolerated; mild-to-moderate hypocalcemia within 1 week post-infusion and transient mild erythrocyturia on the infusion day were the primary adverse reactions.Conclusion:The Chi-BEAM regimen combined with ASCT demonstrates both safety and clinical benefit in patients with high-risk or relapsed/refractory lymphoma.

Objective: Machine learning (ML) has been reported to have better predictive capability than traditional statistical techniques. The aim of this study was to assess the efficacy of ML algorithms and logistic regression (LR) for predicting depressive symptoms during the COVID-19 pandemic. Methods: Analyses were carried out in a national cross-sectional study involving 21,916 participants. The ML algorithms in this study included random forest (RF), support vector machine (SVM), neural network (NN), and gradient boosting machine (GBM) methods. The performance indices were sensitivity, specificity, accuracy, precision, F1-score, and area under the receiver operating characteristic curve (AUC). Results: LR and NN had the best performance in terms of AUCs. The risk of overfitting was found to be negligible for most ML models except for RF, and GBM obtained the highest sensitivity, specificity, accuracy, precision, and F1-score. Therefore, LR, NN, and GBM models ranked among the best models. Conclusion Compared with ML models, LR model performed comparably to ML models in predicting depressive symptoms and identifying potential risk factors while also exhibiting a lower risk of overfitting.

Objective: Machine learning (ML) has been reported to have better predictive capability than traditional statistical techniques. The aim of this study was to assess the efficacy of ML algorithms and logistic regression (LR) for predicting depressive symptoms during the COVID-19 pandemic. Methods: Analyses were carried out in a national cross-sectional study involving 21,916 participants. The ML algorithms in this study included random forest (RF), support vector machine (SVM), neural network (NN), and gradient boosting machine (GBM) methods. The performance indices were sensitivity, specificity, accuracy, precision, F1-score, and area under the receiver operating characteristic curve (AUC). Results: LR and NN had the best performance in terms of AUCs. The risk of overfitting was found to be negligible for most ML models except for RF, and GBM obtained the highest sensitivity, specificity, accuracy, precision, and F1-score. Therefore, LR, NN, and GBM models ranked among the best models. Conclusion Compared with ML models, LR model performed comparably to ML models in predicting depressive symptoms and identifying potential risk factors while also exhibiting a lower risk of overfitting.

Objective:To investigate the associations between MRI texture features and genetic mutations in clear cell renal cell carcinoma (ccRCC) and non-ccRCC (n-ccRCC).Methods:This was a cross-section study. A retrospective review was performed on 31 patients (ccRCC group 19 cases and n-ccRCC group 12 cases) diagnosed with renal cell carcinomas and underwent targeted sequencing between April 2011 and December 2021 in the Third Affiliated Hospital of Soochow University. All the patients underwent MRI examinations within two weeks before partial or radical nephrectomy. Texture features were extracted from T 1WI, T 2WI, Dixon-MRI, cortical-medulla phase (CMP), nephrographic phase (NGP), and delayed phase (DEP) images. MRI texture features with the highest value for distinguishing ccRCC from n-ccRCC were selected for subsequent analysis. The next-generation high-throughput sequencing technology was employed to analyze gene mutations in renal tumors. The correlation between mutation genes and texture features in ccRCC and n-ccRCC was analyzed using Spearman correlation coefficient. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation analysis was performed. Results:A total of 8 MRI texture features were selected. In the ccRCC group, PTEN mutation was correlated with DEP_InverseDifferenceMoment_angle0_offset7 ( r=-0.58, P=0.009). In the non-ccRCC group, SETD2 mutation was correlated with CM_Phase_InverseDifferenceMoment_AllDirection_offset1 and Dixon_W_InverseDifferenceMoment_AllDirection_offset7 ( r=0.58, 0.63, P=0.048, 0.027), PBRM1 mutation was correlated with DE_Phase_InverseDifferenceMoment_angle0_offset7 and DE_Phase_HaraVariance ( r=0.61, -0.60, P=0.034, 0.039), and FAT1 mutation was correlated with DE_Phase_HaraVariance and NG_Phase_Inertia_angle135_offset4 ( r=0.58, 0.58, P=0.047, 0.047). The KEGG pathway annotation analysis showed that the mechanisms of the mutation genes that correlated with MRI texture features in the ccRCC group were related to the p53 signaling pathway, inositol phosphate metabolism, central carbon metabolism in cancer, EGFR tyrosine kinase inhibitor resistance, PD-L1 expression and PD-1 checkpoint pathway in cancer, and phosphatidylinositol signaling system. The mutation genes correlated with MRI texture features in the non-ccRCC group were mainly associated with lysine degradation. Conclusion:The associations are found between MRI texture features and underlying genetic mutations of ccRCC and n-ccRCC. These mutation genes have completely different enrichment pathways.

Objective:To explore the value of four-dimensional flow (4D Flow) MRI in evaluating hemodynamic changes of transplant renal artery stenosis (TRAS).Methods:The study was a cross-sectional study. A retrospective analysis of 67 patients after renal transplantation was performed in Third Affiliated Hospital of Soochow University from January 2021 to October 2022. All patients were examined with non-contrast enhanced magnetic resonance angiography (NCE-MRA) and 4D Flow MRI. After NCE-MRA assessment, the patients were divided into a non stenosis group (39 cases), non-obvious stenosis group (stenosis degree<50%, 13 cases) and obvious stenosis group (stenosis degree≥50%, 15 cases). The 4D Flow MRI data were analyzed using the post-processing software CVI42 (Canada) to measure hemodynamic parameters of the transplanted renal artery in the non-stenosis group, as well as the proximal, central, and distal regions of the stenosis in the non-obvious stenosis group and obvious stenosis group. The parameters included net flow rate, maximum flow rate, average velocity, peak velocity, average wall shear stress, and maximum wall shear stress. One way analysis of variance and least significant difference (LSD) were used to test the differences of hemodynamic parameters among the three groups and between the proximal, central and distal regions of the stenosis. Pearson correlation coefficient was used to evaluate the correlation between hemodynamic parameters of transplant renal artery and estimated glomerular filtration rate (eGFR).Results:The net flow, maximum flow and average velocity at the proximal region of stenosis in the group with obvious stenosis of transplanted renal artery were significantly lower than those in the non-stenosis group and the non-obvious stenosis group (all P<0.05). The net flow and maximum flow at the distal region of stenosis in both obvious stenosis group and non-obvious stenosis group were lower than those in non-stenosis group, and the differences were statistically significant (both P<0.001). The mean velocity and peak velocity at the distal region of stenosis in the obvious stenosis group were higher than those in the non-stenosis group, and the differences were statistically significant (both P<0.05). The maximum and average wall shear stress at the distal region of stenosis in the obvious stenosis group were lower than those in the non-stenosis group and the non-obvious stenosis group, and the differences were statistically significant (both P<0.05). The net flow and maximum flow in the center region of stenosis were lower than those in the proximal region of stenosis, and the differences were statistically significant (both P<0.05). The peak velocity in the center region and distal region of stenosis was higher than those in the proximal region of stenosis, and the difference was statistically significant (both P<0.05). There was a positive correlation between the net flow and eGFR at the TRAS patients proximal, center, and distal stenosis ( r=0.270, 0.260, 0.320, respectively, P=0.044, 0.041, 0.036, respectively). There was a positive correlation between the maximum flow and eGFR at the TRAS patients proximal, center, and distal stenosis ( r=0.306, 0.276, 0.269, respectively, P=0.037, 0.041, 0.043, respectively). Conclusion:After TRAS, there is a significant change in blood flow status. The 4D Flow MRI can provide quantitative hemodynamic parameters to reflect the hemodynamic changes of TRAS.

Objective:To explore the correlation between renal function and abdominal aortic hemodynamic parameters based on four-dimensional flow(4D Flow) MRI in patients with chronic kidney disease (CKD).Methods:A cross-section prospective study was conducted on 73 patients diagnosed with CKD at First People′s Hospital of Changzhou between March 2021 and May 2023, as well as 13 volunteers without kidney injury. According to the estimated glomerular filtration rate (eGFR), the subjects were divided into CKD 1-3 stage group ( n=34), CKD 4-5 stage group ( n=39), and control group ( n=13). All subjects underwent 4D Flow MRI examination of the abdominal aorta, measuring pulse wave velocity (PWV), peak velocity, and maximum wall shear stress (WSS) at the proximal plane (Plane_1) and the higher renal artery opening plane (Plane_2) of the abdominal aorta. The differences in 4D Flow MRI hemodynamic parameters among the three groups were compared using a one-way analysis of variance or the Kruskal-Wallis test. The correlation between 4D Flow MRI hemodynamic parameters and eGFR was analyzed by using the Spearman correlation coefficient. The independent influencing factors that affect eGFR were analyzed by using multivariate linear regression analysis. Results:There were significant differences in abdominal aortic PWV and maximal WSS of Plane_1 and Plane_2 among the three groups ( H=10.38, P=0.006; F=11.16, P<0.001; F=4.75, P=0.011). There were no significant differences in the peak velocity of Plane_1 and Plane_2 among the three groups (both P>0.05). Abdominal aortic PWV was negatively correlated with eGFR ( r s=-0.30, P=0.005). There was a positive correlation between the maximal WSS of Plane_1 and Plane_2 with eGFR ( r s=0.39, P<0.001; r s=0.29, P=0.006). Abdominal aortic PWV and maximal WSS of Plane_1 were independent influencing factors of eGFR (b=-4.32, P=0.018; b=132.23, P=0.004). Conclusions:There is an independent correlation between renal function and abdominal aortic hemodynamic parameters based on 4D Flow MRI in patients with CKD, and abdominal aortic PWV and maximal WSS of Plane_1 were independent influencing factors of eGFR.