Based on spleen deficiency-phlegm dampness as the core pathogenesis of obesity， and integrating recent advances in modern medicine regarding the key role of immune inflammation in obesity， this paper proposes a multidimensional pathogenic network of "obesity-spleen deficiency-phlegm dampness-immune imbalance". Various traditional Chinese medicine （TCM） herbs that strengthen the spleen， regulate qi， and resolve phlegm and dampness can treat obesity by improving spleen-stomach transport and transformation， promoting water-damp metabolism， and regulating immune homeostasis. This highlights immune inflammation as an important entry point to elucidate the TCM concepts of "spleen deficiency-phlegm dampness" and the therapeutic principle of "strengthening the spleen and eliminating dampness to treat obesity". By systematically analyzing the intrinsic connection between "spleen deficiency generating dampness， internal accumulation of phlegm dampness" and immune dysregulation in obesity， this paper aims to provide theoretical support for TCM treatment of obesity based on dampness.

Objective To investigate the effects of Icariin(ICA)on the proliferation,angiogenesis,and migration of human retinal pigment epithelial(RPE)cells in a high-glucose environment and its mechanism.Methods ARPE-19 cells in good growth state were selected and divided into five groups:control group(Control group),high glucose group(HG group),high glucose+low-dose Icariin group(HG+ICA-L group),high glucose+medium-dose Icariin group(HG+ICA-M group),and high glucose+high-dose Icariin group(HG+ICA-H group).The cells in the control group were cul-tured in a medium containing 5.5 mmol·L-1 glucose.Cells in the HG group were cultured in a medium containing 30.0 mmol·L-1 glucose.The cells in each ICA intervention group were first cultured in a medium containing 30.0 mmol·L-1 glucose,and then 10.0 μmol·L-1,20.0 μmol·L-1 and 40.0 μmol·L-1 ICA were added for culture,respectively.The CCK-8 assay was used to detect cell proliferation activity,the EdU assay was used to detect cell proliferation,the Transwell assay was used to detect cell migration ability,and the Matrigel assay was used to detect in vitro tube formation ability.The expression levels of α-smooth muscle actin(α-SMA),matrix metalloproteinase-2(MMP-2),vascular endothelial growth factor A(VEGFA),epidermal growth factor receptor(EGFR),and proteins related to the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway were detected by Western blot.Results The cell viability and EdU-positive rate of ARPE-19 cells in the HG group were higher than those in the Control group(all P＜0.05).The cell viability and EdU-positive rate in the HG+ICA-L,HG+ICA-M,and HG+ICA-H groups were lower than those in the HG group(all P＜0.05).The number of migrated cells and tubes formed in the HG+ICA-L,HG+ICA-M,and HG+ICA-H groups were less than those in the HG group,and the expression levels of α-SMA,MMP-2,VEGFA,and EGFR proteins were lower than those in the HG group(all P＜0.05).The levels of p-PI3K and p-Akt in the HG+ICA-L,HG+ICA-M,and HG+ICA-H groups were lower than those in the HG group(all P＜0.05).Conclusion ICA inhibits the proliferation,migration,and angiogenesis of ARPE-19 cells stimulated by high glucose by suppressing the activation of the PI3K/Akt pathway.

Acute kidney injury (AKI) is one of the most common complications in critically ill patients, and sepsis is the main cause of AKI in the intensive care unit (ICU), which can lead to a poor prognosis in severe cases. For patients with sepsis-associated acute kidney injury (SA-AKI) for whom urgent dialysis is indicated, it is now clear that renal replacement therapy (RRT) can be initiated immediately to control disease progression. However, the optimal timing to initiate RRT in patients whose disease is not severe enough to warrant urgent dialysis remains controversial. Some previous studies were small and heterogeneous, and there was a lack of effective reference indicators for guiding RRT in SA-AKI patients. Therefore, this article reviews the relevant experimental studies on the treatment of critically ill patients with AKI in recent years, and reviews the latest research progress on the optimal timing of RRT initiation, in order to provide an effective reference for clinical practice.
Humans ; Acute Kidney Injury/etiology* ; Renal Replacement Therapy/methods* ; Sepsis/therapy* ; Time Factors ; Intensive Care Units

Objective To investigate the effects of Icariin(ICA)on the proliferation,angiogenesis,and migration of human retinal pigment epithelial(RPE)cells in a high-glucose environment and its mechanism.Methods ARPE-19 cells in good growth state were selected and divided into five groups:control group(Control group),high glucose group(HG group),high glucose+low-dose Icariin group(HG+ICA-L group),high glucose+medium-dose Icariin group(HG+ICA-M group),and high glucose+high-dose Icariin group(HG+ICA-H group).The cells in the control group were cul-tured in a medium containing 5.5 mmol·L-1 glucose.Cells in the HG group were cultured in a medium containing 30.0 mmol·L-1 glucose.The cells in each ICA intervention group were first cultured in a medium containing 30.0 mmol·L-1 glucose,and then 10.0 μmol·L-1,20.0 μmol·L-1 and 40.0 μmol·L-1 ICA were added for culture,respectively.The CCK-8 assay was used to detect cell proliferation activity,the EdU assay was used to detect cell proliferation,the Transwell assay was used to detect cell migration ability,and the Matrigel assay was used to detect in vitro tube formation ability.The expression levels of α-smooth muscle actin(α-SMA),matrix metalloproteinase-2(MMP-2),vascular endothelial growth factor A(VEGFA),epidermal growth factor receptor(EGFR),and proteins related to the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway were detected by Western blot.Results The cell viability and EdU-positive rate of ARPE-19 cells in the HG group were higher than those in the Control group(all P＜0.05).The cell viability and EdU-positive rate in the HG+ICA-L,HG+ICA-M,and HG+ICA-H groups were lower than those in the HG group(all P＜0.05).The number of migrated cells and tubes formed in the HG+ICA-L,HG+ICA-M,and HG+ICA-H groups were less than those in the HG group,and the expression levels of α-SMA,MMP-2,VEGFA,and EGFR proteins were lower than those in the HG group(all P＜0.05).The levels of p-PI3K and p-Akt in the HG+ICA-L,HG+ICA-M,and HG+ICA-H groups were lower than those in the HG group(all P＜0.05).Conclusion ICA inhibits the proliferation,migration,and angiogenesis of ARPE-19 cells stimulated by high glucose by suppressing the activation of the PI3K/Akt pathway.

Purpose To investigate the feasibility of multi-sequence MRI-based radiomics for predicting epidermal growth factor receptor(EGFR)mutation status in brain metastases from non-small cell lung cancer(NSCLC).Materials and Methods This retrospective study included 237 patients with NSCLC brain metastases from the Second Xiangya Hospital of Central South University(January 1,2017 to December 31,2023)who underwent EGFR genetic testing.All patients underwent pretreatment brain MRI including contrast-enhanced T1-weighted,T2-weighted FLAIR,and T2-weighted sequences,along with chest CT for primary lung lesions.EGFR mutations were identified in 120 patients.Using December 31,2021 as the cutoff date,patients were divided into training(n=146)and validation(n=91)cohorts.Senior radiologists delineated brain metastases on multi-sequence MRI and primary lesions on CT.A total of 851 radiomic features were extracted using PyRadiomics.Following feature selection,machine learning models were constructed using support vector machine algorithm and compared with least absolute shrinkage and selection operator-derived radiomic signatures.Five models were developed:three single-sequence MRI models,a multi-sequence MRI fusion model,and a CT model,with diagnostic performance evaluated by area under the receiver operating characteristic curve.Results The multi-sequence MRI fusion model demonstrated superior performance across all imaging types.The least absolute shrinkage and selection operator and support vector machine models achieved training set area under the curve of 0.854(95%CI 0.748-0.960)and 0.948(95%CI 0.923-0.973),respectively,and validation set area under the curve of 0.810(95%CI 0.751-0.869)and 0.951(95%CI 0.917-0.985),respectively.The optimal prediction model utilized support vector machine algorithm with multi-sequence MRI features.Conclusion Pretreatment multi-sequence MRI radiomics combined with machine learning accurately predicts EGFR mutation status in NSCLC patients with brain metastases.

Objective:To investigate the therapeutic efficacy and safety of conditioning regimen with oral melphalan in tandem autologous hematopoieticstem cell transplantation (ASCT) for patients with malignant plasma cell diseases.Methods:A retrospective case series study was conducted. The clinical data of 13 patients with malignant plasma cell diseases who underwent tandem ASCT between October 2019 and March 2024 in the First Affiliated Hospital of Xi'an Jiaotong University were collected. Compared with the use of intravenous melphalan as conditioning regimen for the first ASCT, hematopoietic reconstruction after transplantation, the therapeutic effects, adverse reactions after drug usage and survival of conditioning regimen with oral melphalan after tandem ASCT were analyzed.Results:Among the 13 patients, there were 10 males and 3 females, with a median age [ M ( Q1, Q3)] of 53 (48, 61) years; 11 cases were multiple myeloma and 2 cases were plasma cell leukemia. Before the first ASCT, tandem ASCT was performed 2-6 months later. The median reconstruction time of neutrophils after the first and second ASCT were both 9 (9, 10) d, and the median reconstruction time of platelets after the first and second ASCT were both 10 (9, 11) d, and there were no statistically significant differences in reconstruction rate of granulocytes on day 9 [69.2% (9/13) vs. 61.5% (8/13)] and platelets on day 10 [46.2% (6/13) vs. 53.8% (7/13)] between the first and second transplantation (all P > 0.05). There were 4 cases of strict complete remission (sCR), 3 cases of complete remission (CR), 4 cases of very good partial remission (VGPR), and 2 cases of partial remission (PR) before the first ASCT. After the first ASCT 1 month later, 1 case achieved VGPR, 1 case achieved PR, 11 cases achieved sCR; all 13 patients achieved sCR at 6 months after second ASCT. Compared with conditioning regimen of intravenous melphalan for the first ASCT, the non-hematological adverse reactions such as nausea (7 cases vs. 9 cases), vomiting (4 cases vs. 13 cases), diarrhea (4 cases vs. 13 cases) and oral mucositis (2 cases vs. 9 cases) in the conditioning regimen of oral melphalan after the second ASCT was reduced, and the differences were statistically significant (all P < 0.01). After the 2 transplantation conditioning regimen with melphalan, Ⅳ degree myelosuppression occurred in 13 cases. After the second ASCT, the median follow-up time was 14 (10, 22) months, 7 patients received maintenance therapy containing lenalidomide, 3 patients received maintenance therapy containing bortezomib, 2 patients received pomalidomide maintenance therapy, and 1 patient received maintenance therapy containing CD38 monoclonal antibody. At the last follow-up, all patients survived, among which 6 multiple myeloma patients relapsed; and the median recurrence time was 13 (10, 22) months after the second ASCT. The estimated 5-year progression-free survival rate was 28.6%. Conclusions:Conditioning regimen with oral melphalan for the second ASCT is safe and well tolerated, and it may further improve the efficacy of the first transplantation.

Objective To observe the value of improved marching cubes(MC)algorithm based on Monte Carlo sampling and multi-feature analysis for reconstructing head and abdominal CT images.Methods Totally 69 head axial CT images from one patient with glioma and 108 abdominal axial CT images from another patient with liver cancer were retrospectively enrolled,while 98 head axial CT images of males in visible human project dataset were included.Monte Carlo sampling and multi-feature analysis were introduced into MC algorithm.Monte Carlo sampling was used to simulate the uncertainty of voxel values and estimate the probability of voxels belonging to the isosurface,and dynamic thresholds were generated through combining gradient,curvature,local variance and distance term features of voxels.Then head and abdominal CT images were reconstructed with improved MC algorithm,which were compared with those reconstructed with traditional MC and probabilistic MC(PMC)algorithms.Results Compared with traditional MC and PMC algorithms,improved MC algorithm had lower mean square error,higher signal-to-noise ratio,peak signal-to-noise ratio and computation time for reconstructing head and abdominal CT images without significant difference of Dice similarity coefficient nor recall rate,which could keep the structural loss rate and morphological change rate at low level.Conclusion Improved MC algorithm based on Monte Carlo sampling and multi-feature analysis could significantly improve the robustness and edge accuracy for reconstructing head and abdominal CT images,but the computational efficiency and preservation of head structural details still needed to be optimized.

Background::B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T (CAR-T) therapy yield remarkable responses in patients with relapsed/refractory multiple myeloma (R/RMM). Circulating tumor DNA (ctDNA) reportedly exhibits distinct advantages in addressing the challenges posed by tumor heterogeneity in the distribution and genetic variations in R/RMM.Methods::Herein, the ctDNA of 108 peripheral blood plasma samples from patients with R/RMM at the First Affiliated Hospital, School of Medicine, Zhejiang University was thoroughly investigated before administration of anti-BCMA CAR-T therapy to establish its predictive potential. Flow cytometry is used primarily to detect subgroups of T cells or CAR-T cells.Results::In this study, several tumor and T cell effector-mediated factors were considered to be related to treatment failure by an integrat analysis, including higher percentages of multiple myeloma (MM) cells in the bone marrow ( P = 0.0125), lower percentages of CAR-T cells in the peripheral blood at peak ( P = 0.0375), and higher percentages of CD8 + T cells ( P = 0.0340). Furthermore, there is a substantial correlation between high ctDNA level (>143 ng/mL) and shorter progression-free survival (PFS) ( P = 0.007). Multivariate Cox regression analysis showed that high levels of ctDNA (>143 ng/mL), MM-driven high-risk mutations (including IGLL5 [ P = 0.004], IRF4 [ P = 0.024], and CREBBP [ P = 0.041]), number of multisite mutations, and resistance-related mutation ( ERBB4, P = 0.040) were independent risk factors for PFS. Conclusion::Finally, a ctDNA-based risk model was built based on the above independent risk factors, which serves as an adjunct non-invasive measure of substantial tumor burden and a prognostic genetic feature that can assist in predicting the response to anti-BCMA CAR-T therapy.

Purpose To investigate the feasibility of multi-sequence MRI-based radiomics for predicting epidermal growth factor receptor(EGFR)mutation status in brain metastases from non-small cell lung cancer(NSCLC).Materials and Methods This retrospective study included 237 patients with NSCLC brain metastases from the Second Xiangya Hospital of Central South University(January 1,2017 to December 31,2023)who underwent EGFR genetic testing.All patients underwent pretreatment brain MRI including contrast-enhanced T1-weighted,T2-weighted FLAIR,and T2-weighted sequences,along with chest CT for primary lung lesions.EGFR mutations were identified in 120 patients.Using December 31,2021 as the cutoff date,patients were divided into training(n=146)and validation(n=91)cohorts.Senior radiologists delineated brain metastases on multi-sequence MRI and primary lesions on CT.A total of 851 radiomic features were extracted using PyRadiomics.Following feature selection,machine learning models were constructed using support vector machine algorithm and compared with least absolute shrinkage and selection operator-derived radiomic signatures.Five models were developed:three single-sequence MRI models,a multi-sequence MRI fusion model,and a CT model,with diagnostic performance evaluated by area under the receiver operating characteristic curve.Results The multi-sequence MRI fusion model demonstrated superior performance across all imaging types.The least absolute shrinkage and selection operator and support vector machine models achieved training set area under the curve of 0.854(95%CI 0.748-0.960)and 0.948(95%CI 0.923-0.973),respectively,and validation set area under the curve of 0.810(95%CI 0.751-0.869)and 0.951(95%CI 0.917-0.985),respectively.The optimal prediction model utilized support vector machine algorithm with multi-sequence MRI features.Conclusion Pretreatment multi-sequence MRI radiomics combined with machine learning accurately predicts EGFR mutation status in NSCLC patients with brain metastases.

Objective To observe the value of improved marching cubes(MC)algorithm based on Monte Carlo sampling and multi-feature analysis for reconstructing head and abdominal CT images.Methods Totally 69 head axial CT images from one patient with glioma and 108 abdominal axial CT images from another patient with liver cancer were retrospectively enrolled,while 98 head axial CT images of males in visible human project dataset were included.Monte Carlo sampling and multi-feature analysis were introduced into MC algorithm.Monte Carlo sampling was used to simulate the uncertainty of voxel values and estimate the probability of voxels belonging to the isosurface,and dynamic thresholds were generated through combining gradient,curvature,local variance and distance term features of voxels.Then head and abdominal CT images were reconstructed with improved MC algorithm,which were compared with those reconstructed with traditional MC and probabilistic MC(PMC)algorithms.Results Compared with traditional MC and PMC algorithms,improved MC algorithm had lower mean square error,higher signal-to-noise ratio,peak signal-to-noise ratio and computation time for reconstructing head and abdominal CT images without significant difference of Dice similarity coefficient nor recall rate,which could keep the structural loss rate and morphological change rate at low level.Conclusion Improved MC algorithm based on Monte Carlo sampling and multi-feature analysis could significantly improve the robustness and edge accuracy for reconstructing head and abdominal CT images,but the computational efficiency and preservation of head structural details still needed to be optimized.