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Lipopolysaccharide stimulates macrophages to secrete exosomes containing miR-155-5p to promote activation and migration of hepatic stellate cells LIN Jiayi, LOU Anni, LI Xu Journal of Southern Medical University    2023, 43 (6): 994-1001.   DOI: 10.12122/j.issn.1673-4254.2023.06.15 Abstract （1467）   HTML （12）    PDF（pc） （3369KB）（271）       Knowledge map    Save Objective To observe the effect of exosomes secreted by lipopolysaccharides (LPS)-stimulated macrophages on hepatic stellate cell activation and migration and explore the underlying molecular mechanism. Methods Human monocyte THP-1 cells were induced to differentiate into macrophages using propylene glycol methyl ether acetic acid (PMA, 100 ng/mL, 24 h) followed by stimulation with LPS, and the culture supernatant of macrophages was collected for extraction of the exosomes by ultracentrifugation. The expression of miR-155-5p in the exosomes was detected using qRT-PCR. A Transwell co-culture system was used to observe the effects of the macrophage-derived exosomes on LX2 cell (a hepatic stellate cell line) proliferation, migration, oxidative stress and the expression of fibrosis biomarkers, which were also observed in LX2 cells transfected with miR-155-5p-mimics or miR-155-5p-inhibitors. Western blotting was used to detect the expressions of SOCS1 and its downstream signal pathway proteins. Results Treatment with the exosomes from LPS-stimulated macrophages significantly enhanced the proliferation and migration ability of LX2 cells and increased the levels of oxidative stress and expressions of the fibrosis markers such as type I collagen (P<0.05). The expression of miR-155-5p in the exosomes secreted by macrophages was significantly increased after LPS treatment (P<0.01). LX2 cells overexpressing miR-155-5p also exhibited significantly enhanced proliferation and migration with increased oxidative stress levels and expression of type I collagen (P<0.05), and interference of miR-155-5p expression produced the opposite effects. Western blotting showed that miR-155-5p overexpression obviously inhibited SOCS1 expression and promoted p-Smad2/3, Smad2/3 and RhoA protein expressions in LX2 cells (P<0.05). Conclusion LPS stimulation of the macrophages increases miR-155-5p expression in the exosomes to promote activation and migration and increase oxidative stress and collagen production in hepatic stellate cells. Related Articles | Metrics | Comments（0）

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Structural changes of the frontal cortex in depressed mice are associated with decreased expression of brain-derived neurotrophic factor CUI Weiwei, GONG Liya, CHEN Chunhui, TANG Jiayu, JIN Xin, LI Zixin, JING Linlin, WEN Ge Journal of Southern Medical University    2023, 43 (6): 1041-1046.   DOI: 10.12122/j.issn.1673-4254.2023.06.22 Abstract （1345）   HTML （15）    PDF（pc） （2616KB）（135）       Knowledge map    Save Objective To investigate the changes in gray matter volume in depressive-like mice and explore the possible mechanism. Methods Twenty- four 6-week-old C57 mice were randomized equally into control group and model group, and the mice in the model group were subjected to chronic unpredictable mild stimulation (CUMS) for 35 days. Magnetic resonance imaging was performed to examine structural changes of the grey matter volume in depressive-like mice. The expression of brain-derived neurotrophic factor (BDNF) in the grey matter of the mice was detected using Western blotting and immunofluorescence staining. Results Compared with the control mice, the mice with CUMS showed significantly decreased central walking distance in the open field test (P<0.05) and increased immobile time in forced swimming test (P<0.05). Magnetic resonance imaging showed that the volume of the frontal cortex was significantly decreased in CUMS mice (P<0.001, when the mass level was greater than or equal to 10 756, the FDRc was corrected with P=0.05). Western blotting showed that the expression of mature BDNF in the frontal cortex was significantly decreased in CUMS mice (P<0.05), and its expression began to decrease after the exposure to CUMS as shown by immunofluorescence staining. The volume of different clusters obtained by voxel-based morphometry (VBM) analysis was correlated with the expression level of mature BDNF detected by Western blotting (P<0.05). Conclusion The decrease of frontal cortex volume after CUMS is related with the reduction of mature BDNF expression in the frontal cortex. Related Articles | Metrics | Comments（0）

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Efficacy and safety of peginterferon-α2b for treatment of myeloproliterative neoplasms LUO Dongmei, LUO Jie, LIANG Hanyin, HE Zherou, CHEN Hong, WEN Ziyu, WANG Qiang, ZHOU Xuan, LIU Xiaoli, XU Na Journal of Southern Medical University    2023, 43 (6): 1029-1034.   DOI: 10.12122/j.issn.1673-4254.2023.06.20 Abstract （1334）   HTML （8）    PDF（pc） （1193KB）（191）       Knowledge map    Save Objective To evaluate the clinical efficacy and adverse reactions of peginterferon-α2b for treatment of chronic myeloproliferative neoplasms (MPN). Methods We retrospectively analyzed the data of 107 patients with MPN, including 95 with essential thrombocythemia (ET) and 12 with polycythemia vera (PV), who all received peginterferon-α2b treatment for at least 12 months. The clnical and follow-up data of the patients were analyzed to evaluate the efficacy and adverse reactions of the treatment. Results After receiving peginterferon- α2b treatment, both ET and PV patients achieved high hematological remission rates, and the total remission rates did not differ significantly between the two groups (86% vs 78%, P>0.05). In the overall patients, the spleen index decreased by 13.5% (95%CI: 8.5%-18.5%) after the treatment. The patients with hematological remission showed a significantly greater reduction of the total symptom score than those without hematological remission (P<0.01). The median percentage of JAK2V617F allele load of PV patients decreased from 67.23% (49.6%-84.86% ) at baseline to 19.7% (0.57%-74.6%) after the treatment, and that of JAK2V617F-positive ET patients decreased from 48.97% (0.45%-74.24%) at baseline to 22.1% (0.33%-65.42% ) after the treatment. Mild adverse reactions (grade 1-2) were observed in both ET and PV groups without significant differences between them. The overall incidence of thrombotic events during the treatment was 2.8% in these patients, and no serious adverse reactions were observed. Conclusion For patients with chronic myelodysplasia, peginterferon-α2b treatment can achieve a high peripheral blood cell remission rate and maintain a long-term stable state with good effect in relieving symptoms such as splenomegaly. Peginterferon-α2b treatment caused only mild adverse reactions, which can be tolerated by most of the patients. Related Articles | Metrics | Comments（0）

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Quantitative evaluation of radiotherapy plan in precise external beam radiotherapy process management for cervical cancer GUOYujun, LI Ting, YANGXin, QI Zhenyu, CHEN Li, HUANG Sijuan Journal of Southern Medical University    2023, 43 (6): 1035-1040.   DOI: 10.12122/j.issn.1673-4254.2023.06.21 Abstract （1311）   HTML （7）    PDF（pc） （883KB）（146）       Knowledge map    Save Objective To identify the problems in clinical radiotherapy planning for cervical cancer through quantitative evaluation of the radiotherapy plans to improve the quality of the plans and the radiotherapy process. Methods We selected the clinically approved and administered radiotherapy plans for 227 cervical cancer patients undergoing external radiotherapy at Sun Yat-sen University Cancer Center from May, 2019 to January, 2022. These plans were transferred from the treatment planning system to the Plan IQTM workstation. The plan quality metrics were determined based on the guidelines of ICRU83 report, the GEC-ESTRO Working Group, and the clinical requirements of our center and were approved by a senior clinician. The problems in the radiotherapy plans were summarized and documented, and those with low scores were re-planned and the differences were analyzed. Results We identified several problems in the 277 plans by quantitative evaluation. Inappropriate target volume selection (with scores<60) in terms of GTV, PGTV (CI) and PGTV (V66 Gy) was found in 10.6%, 65.2%, and 1% of the plans, respectively; and the PGTV (CI), GTV, and PCTV (D98%, HI) had a score of 0 in 0.4%, 10.1%, 0.4%, 0.4% of the plans, respectively. The problems in the organs at risk (OARs) involved mainly the intestines (the rectum, small intestine, and colon), found in 20.7% of the plans, and in occasional cases, the rectum, small intestine, colon, kidney, and the femoral head had a score of 0. Senior planners showed significantly better performance than junior planners in PGTV (V60 Gy, D98% ), PCTV (CI), and CTV (D98% ) (P≤0.046) especially in terms of spinal cord and small intestine protection (P≤0.034). The bowel (the rectum, small intestine and colon) dose was significantly lower in the prone plans than supine plans (P<0.05), and targets coverage all met clinical requirements. Twenty radiotherapy plans with low scores were selected for re-planning. The re-planned plans had significantly higher GTV (Dmin) and PTV (V45 Gy, D98% ) (P<0.05) with significantly reduced doses of the small intestines (V40 Gy vs V30 Gy), the colon (V40 Gy vs V30 Gy), and the bladder (D35%) (P<0.05). Conclusion Quantitative evaluation of the radiotherapy plans can not only improve the quality of radiotherapy plan, but also facilitate risk management of the radiotherapy process. Related Articles | Metrics | Comments（0）

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Efficacy of machine learning models versus Cox regression model for predicting prognosis of esophagogastric junction adenocarcinoma GAO Kaiji, WANG Yihao, CAO Haikun, JIA Jianguang Journal of Southern Medical University    2023, 43 (6): 952-963.   DOI: 10.12122/j.issn.1673-4254.2023.06.10 Abstract （1249）   HTML （9）    PDF（pc） （2472KB）（246）       Knowledge map    Save Objective To compare the performance of machine learning models and traditional Cox regression model in predicting postoperative outcomes of patients with esophagogastric junction adenocarcinoma (AEG). Methods This study was conducted among 203 AEG patients with complete clinical and follow-up data, who were treated in our hospital between September, 2015 and October, 2020. The clinicopathological data of the patients were processed for analysis using R language package and divided into training and validation datasets at the ratio of 3∶1. The Cox proportional hazards regression model and 4 machine learning models were constructed for analyzing the datasets. ROC curves, calibration curves and clinical decision curves (DCA) were plotted. Internal validation of the machine learning models was performed to assess their predictive efficacy. The predictive performance of each model was evaluated by calculating the area under the curve (AUC), and the model fitting was assessed using the calibration curve. Results For predicting 3-year survival based on the validation dataset, the AUC was 0.870 for Cox proportional hazard regression model, 0.901 for eXtreme Gradient Boosting (XGBoost), 0.791 for random forest, 0.832 for support vector machine, and 0.725 for multilayer perceptron; For predicting 5-year survival, the AUCs of these models were 0.915, 0.916, 0.758, 0.905, and 0.737, respectively. For internal validation, the AUCs of the 4 machine learning models decreased in the order of XGBoost (0.818), random forest (0.758), support vector machine (0.0.804), and multilayer perceptron (0.745). Conclusion The machine learning models show better predictive efficacy for survival outcomes of patients with AEG than Cox proportional hazard regression model, especially when proportional odds assumption or linear regression models are not applicable. XGBoost models have better performance than the other machine learning models, and the multi-layer perception model may have poor fitting results for a limited data volume. Related Articles | Metrics | Comments（0）

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Therapeutic mechanism of Shenbing Decoction III for renal fibrosis in chronic kidney disease: a study with network pharmacology, molecular docking and validation in rats LUO Guanfeng, LIU Huaxi, XIE Bei, DENG Yijian, XIE Penghui, ZHAO Xiaoshan, SUN Xiaomin Journal of Southern Medical University    2023, 43 (6): 924-934.   DOI: 10.12122/j.issn.1673-4254.2023.06.07 Abstract （1209）   HTML （15）    PDF（pc） （4146KB）（261）       Knowledge map    Save Objective To observe the effect of Shenbing Decoction III for improving renal function and pathology in rats with 5/6 nephrectomy and analyze its therapeutic mechanism for renal fibrosis in chronic kidney disease using network pharmacology combined with molecular docking. Methods Forty male SD rats were randomized into two groups to receive two-staged 5/6 nephrectomy (n=30) or sham operation (n=10), and 2 weeks after the final operation, serum creatinine level of the rats was measured. The rats with nephrectomy were further randomized into Shenbing Decoction III group, losartan group and model group for daily treatment with the corresponding drugs via gavage starting at 1 week after 5/6 nephrectomy. After 16 weeks of treatment, serum creatinine and urea nitrogen levels of the rats were measured, and HE staining and Western blotting were used to examine the changes in renal pathology and fibrosis-related factors. Network pharmacology combined with molecular docking study was performed to explore the therapeutic mechanism Shenbing Decoction III against renal fibrosis in chronic kidney disease, and Western blotting was used to verify the expressions of the core targets. Results Compared with those in the model group, the rats receiving 5/6 nephrectomy and Shenbing Decoction III treatment showed significantly reduced serum creatinine and urea nitrogen levels, lessened renal pathologies, and improvement of the changes in epithelial mesenchymal transition-related proteins. Network pharmacological analysis showed that the main active ingredients of Shenbing Decoction III were acacetin, apigenin, eupatilin, quercetin, kaempferol and luteolin, and the key targets included STAT3, SRC, CTNNB1, PIK3R1 and AKT1. Molecular docking study revealed that the active ingredients of Shenbing Decoction III had good binding activity to the key targets. Western blotting showed that in rats with 5/6 nephrectomy, treatment with Shenbing Decoction III obviously restored the protein expression of STAT3, PI3K, and AKT in renal tissue. Conclusion Shenbing Decoction III can reduce renal injury induced by 5/6 nephrectomy in rats, and its therapeutic effects are mediated possibly by its main pharmacologically active ingredients that alleviate renal fibrosis via modulating multiple targets including STAT3, PIK3R1, and AKT1. Related Articles | Metrics | Comments（0）

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Prediction of 1p/19q codeletion status in diffuse lower-grade glioma using multimodal MRI radiomics LU Mingjun, QU Yaoming, MA Andong, ZHU Jianbin, ZOU Xia, LIN Gengyun, LI Yuxin, LIU Xinzi, WEN Zhibo Journal of Southern Medical University    2023, 43 (6): 1023-1028.   DOI: 10.12122/j.issn.1673-4254.2023.06.19 Abstract （1205）   HTML （27）    PDF（pc） （1023KB）（200）       Knowledge map    Save Objective To develop a noninvasive method for prediction of 1p/19q codeletion in diffuse lower-grade glioma (DLGG) based on multimodal magnetic resonance imaging (MRI) radiomics. Methods We collected MRI data from 104 patients with pathologically confirmed DLGG between October, 2015 and September, 2022. A total of 535 radiomics features were extracted from T2WI, T1WI, FLAIR, CE-T1WI and DWI, including 70 morphological features, 90 first order features, and 375 texture features. We constructed logistic regression (LR), logistic regression least absolute shrinkage and selection operator (LRlasso), support vector machine (SVM) and Linear Discriminant Analysis (LDA) radiomics models and compared their predictive performance after 10- fold cross validation. The MRI images were reviewed by two radiologists independently for predicting the 1p/19q status. Receiver operating characteristic curves were used to evaluate classification performance of the radiomics models and the radiologists. Results The 4 radiomics models (LR, LRlasso, SVM and LDA) achieved similar area under the curve (AUC) in the validation dataset (0.833, 0.819, 0.824 and 0.819, respectively; P>0.1), and their predictive performance was all superior to that of resident physicians of radiology (AUC=0.645, P=0.011, 0.022, 0.016, 0.030, respectively) and similar to that of attending physicians of radiology (AUC=0.838, P>0.05). Conclusion Multiparametric MRI radiomics models show good performance for noninvasive prediction of 1p/19q codeletion status in patients with in diffuse lower-grade glioma. Related Articles | Metrics | Comments（0）

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UPLC-Q-TOF-MS/MS combined with network pharmacology for exploring anti-inflammatory mechanism of Eurycoma longifolia LIU Fang, ZHANG Yuanfang, LIU Peng, LIU Jiamin, LIU Siyu, WANG Junjie Journal of Southern Medical University    2023, 43 (6): 879-888.   DOI: 10.12122/j.issn.1673-4254.2023.06.02 Abstract （1061）   HTML （17）    PDF（pc） （2673KB）（190）       Knowledge map    Save Objective To explore the mechanisms that mediate the anti-inflammatory activity of Eurycoma longifolia. Methods Kunming mouse models of xylene-induced ear swelling and lipopolysaccharide (LPS)-induced acute pneumonia were used to compare the anti- inflammatory activities of aqueous and ethanol extracts of Eurycoma longifolia. UPLC-Q-TOF-MS/MS was used to identify the chemical composition in the ethanol extract of Eurycoma longifolia, based on which the potential anti-inflammatory targets of Eurycoma longifolia were screened using the databases including SwissADME, SwissTargetPrediction, and Genecards. The String database was used to generate the protein-protein interaction (PPI) network, and Cytoscape was used for network topology analysis and screening the core targets. The enrichment of the core targets was analyzed using Metascape database, the core components and targets were docked with Autodock software, and the docking results were visualized using Pymol software. In a RAW264.7 cell model of LPS-induced inflammation, the Griess reagent was used to measure NO level, and Western blotting was performed to detect the expression levels of MAPK1, JAK2, and STAT3 proteins to verify the anti- inflammatory mechanism of Eurycoma longifolia. Results The ethanol extract (75% ) of Eurycoma longifolia (ELE) was the active site, which contained a total of 37 chemical components. These chemical compounds and diseases had 541 targets, involving the JAK/STAT3, cAMP and other signaling pathways. Twelve indicator components were identified, which all showed good results of molecular docking with two core targets involved in the signaling pathways. In the cell validation experiment, treatment of the cells with low-, medium-, and high-dose ELE significantly reduced NO release in the cells, and ELE at the medium dose significantly decreased the cellular expressions of JAK2 and STAT3. Conclusion The anti-inflammatory activity of Eurycoma longifolia is attributed primarily to its active ingredients bitter lignin and alkaloids, which may regulate the JAK/STAT3 signaling pathway by targeting JAK2 and STAT3. Related Articles | Metrics | Comments（0）

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Role of gut microbiota in perioperative neurocognitive disorders after cardiopulmonary bypass surgery in rats with humanized gut flora FAN Jianing, SUN Yingjie, LIANG Bing, ZHANG Xiaoyan, XIAO Cheng, HUANG Zeqing Journal of Southern Medical University    2023, 43 (6): 964-969.   DOI: 10.12122/j.issn.1673-4254.2023.06.11 Abstract （982）   HTML （11）    PDF（pc） （1081KB）（215）       Knowledge map    Save Objective To investigate whether gut microbiota disturbance after cardiopulmonary bypass (CPB) contributes to the development of perioperative neurocognitive disorders (PND). Methods Fecal samples were collected from healthy individuals and patients with PND after CPB to prepare suspensions of fecal bacteria, which were transplanted into the colorectum of two groups of pseudo-germ-free adult male SD rats (group NP and group P, respectively), with the rats without transplantation as the control group (n=10). The feces of the rats were collected for macrogenomic sequencing analysis, and serum levels of IL-1β, IL-6 and TNF-α were measured with ELISA. The expression levels of GFAP and p-Tau protein in the hippocampus of the rats were detected using Western blotting, and the cognitive function changes of the rats were assessed with Morris water maze test. Results In all the 3 groups, macrogenomic sequencing analysis showed clustering and clear partitions of the gut microbiota after the transplantation. The relative abundances of Klebsiella in the control group (P<0.005), Akkermansia in group P (P<0.005) and Bacteroides in group NP (P<0.005) were significantly increased after the transplantation. Compared with those in the control group, the rats in group NP and group P showed significantly decreased serum levels of IL-1β, IL-6 and TNF-α and lowered expression levels of GFAP and p-Tau proteins (all P<0.05). Escape platform crossings and swimming duration in the interest quadrant increased significantly in group NP (P<0.05), but the increase was not statistically significant in group N. Compared with those in group P, the rats in group NP had significantly lower serum levels of IL-1β, IL-6 and TNF-α and protein expressions of GFAP and p-Tau (all P<0.05) with better performance in water maze test (P<0.05). Conclusion In patients receiving CPB, disturbances in gut mirobiota contributes to the development of PND possibly in relation with inflammatory response. Related Articles | Metrics | Comments（0）

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Colorectal cancer cells induce the formation of cancer-associated fibroblasts by activating the ERK signaling pathway in fibroblasts DENG Ting, DU Boyu, XI Xueyan Journal of Southern Medical University    2023, 43 (6): 943-951.   DOI: 10.12122/j.issn.1673-4254.2023.06.09 Abstract （931）   HTML （11）    PDF（pc） （2225KB）（319）       Knowledge map    Save Objective To investigate the mechanism by which conditioned medium of colorectal cancer cells promotes the formation of cancer-associated fibroblasts (CAFs). Methods Normal human colorectal fibroblasts (CCD-18Co cells) in logarithmic growth phase were treated with the conditioned media of colorectal cancer HCT116 cells (HCT116-CM) or Caco-2 cells (Caco-2-CM) alone or in combination with 300 nmol/L ERK inhibitor SCH772984. The expression levels of CAFs-related molecular markers were detected in the treated cells with real-time quantitative PCR (RT- qPCR) and immunofluorescence assay, and the changes in cell proliferation, colony formation and migration were assessed with RTCA, colony formation and wound healing assays; Western blotting was performed to detect the activated signaling pathways in the fibroblasts and the changes in CAFs formation after blocking of the signaling pathway. Results HCT116-CM and Caco-2-CM significantly up-regulated mRNA expression levels of CAFs markers (including α-SMA, FAP, FN and TGF-β) in CCD-18Co cells, and strongly promoted fibroblast transformation into CAFs (P<0.05). The two conditioned media also promoted the proliferation, colony formation and migration of CCD-18Co cells (P<0.05) and significantly increased the levels of α-SMA protein and ERK phosphorylation in the cells (P<0.05). The ERK inhibitor SCH772984 obviously inhibited the expression of α-SMA and the transformation of CCD-18Co cells into CAFs induced by the conditioned medium of colorectal cancer cells (P<0.05). Conclusion Colorectal cancer cells may induce the formation of colorectal CAFs by activating the ERK pathway in the fibroblasts. Related Articles | Metrics | Comments（0）

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Expression of TUBB4B in mouse primary spermatocyte GC-2 cells and its regulatory effect on NF-κB and MAPK signaling pathway LIU Tongjia, WANG Wanlun, ZHANG Ting, LIU Shuang, BIAN Yanchao, ZHANG Chuanling, XIAO Rui Journal of Southern Medical University    2023, 43 (6): 1002-1009.   DOI: 10.12122/j.issn.1673-4254.2023.06.16 Abstract （756）   HTML （15）    PDF（pc） （2416KB）（165）       Knowledge map    Save Objective To explore the interaction between Tubulin beta 4B class IVb (TUBB4B) and Agtpbp1/cytosolic carboxypeptidase- like1 (CCP1) in mouse primary spermatocytes (GC-2 cells) and the role of TUBB4B in regulating the development of GC-2 cells. Methods Lentiviral vectors were used to infect GC-2 cells to construct TUBB4B knockdown and negative control (NC-KD) cells. The stable cell lines with TUBB4B overexpression (Tubb4b-OE) and the negative control (NC-OE) cells were screened using purinomycin. RT-qPCR and Western blotting were used to verify successful cell modeling and explore the relationship between TUBB4B and CCP1 expressions in GC-2 cells. The effects of TUBB4B silencing and overexpression on the proliferation and cell cycle of GC-2 cells were evaluated using CCK8 assay and flow cytometry. The signaling pathway proteins showing significant changes in response to TUBB4B silencing or overexpression were identified using Western blotting and immunofluorescence assay and then labeled for verification at the cellular level. Results Both TUBB4B silencing and overexpression in GC-2 cells caused consistent changes in the mRNA and protein expressions of CCP1 (P<0.05). Similarly, TUBB4B expression also showed consistent changes at the mRNA and protein after CCP1 knockdown and restoration (P<0.05). TUBB4B knockdown and overexpression had no significant effect on proliferation rate or cell cycle of GC-2 cells, but caused significant changes in the key proteins of the nuclear factor kappa-B (NF-κB) signaling pathway (p65 and p-p65) and the mitogen-activated protein kinase (MAPK) signaling pathway (ErK1/2 and p-Erk1/2) (P<0.05); CCP1 knockdown induced significant changes in PolyE expression in GC-2 cells (P<0.05). Conclusions TUBB4B and CCP1 interact via a mutual positive regulation mechanism in GC-2 cells. CCP-1 can deglutamize TUBB4B, and the latter is involved in the regulation of NF-κB and MAPK signaling pathways in primary spermatocytes. Related Articles | Metrics | Comments（0）

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Alveolar nitric oxide concentration has a potential value in the diagnosis and differential diagnosis of interstitial lung diseases CHANG Xiaodan, CHEN Meijia, LIAO Hua, DONG Hanming, CAI Shaoxi Journal of Southern Medical University    2023, 43 (8): 1410-1416.   DOI: 10.12122/j.issn.1673-4254.2023.08.19 Abstract （573）   HTML （8）    PDF（pc） （925KB）（82）       Knowledge map    Save Objective To investigate the value of exhaled nitric oxide (eNO) in the diagnosis and differential diagnosis of interstitial lung disease (ILD). Methods This study was conducted among 45 patients with interstitial lung disease, including 18 with connective tissue disease- related ILD (CTD- ILD) and 27 with non-CTD-ILD, with 68 healthy subjects as the control group. According to European Respiratory Association Guidelines, alveolar nitric oxide (CaNO) concentration and fractional exhaled nitric oxide (FeNO) level were measured at the flow rates of 50 and 200 mL/s. The predictive level of CaNO was analyzed using receiver-operating characteristic curve (ROC), and the correlations between CaNO and pulmonary function indicators were examined in the patients with ILD. Results CaNO, FeNO50, and FeNO200 levels were significantly higher in patients with ILD than in the healthy controls. Logistic regression analysis showed that lowered levels of CaNO and FeNO200 were risk factors for ILD. ROC curve analysis showed that the area under the curve (AUC) of CaNO combined with FeNO200 was 0.829 (95% CI: 0.752-0.906) for the diagnosis of ILD. In patients with ILD, CaNO levels were negatively correlated with DLCO%pred (r=-0.471, P<0.05). Subgroup comparison showed a significantly higher CaNO level in CTD- ILD group than in non-CTD- ILD group. The AUC for CaNO to discriminate CTD- ILD from non-CTD-ILD was 0.725 (95% CI: 0.576 to 0.875). Conclusion CaNO has a potential value in the diagnosis of ILD and differential diagnosis of CTD-ILD. Related Articles | Metrics | Comments（0）

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Value of Improved Mayo Endoscopic Score for evaluating treatment efficacy for active ulcerative colitis SONG Zejun, DONG Haibin, MA Na, REN Yutang, JIANG Bo Journal of Southern Medical University    2023, 43 (7): 1204-1213.   DOI: 10.12122/j.issn.1673-4254.2023.07.17 Abstract （568）   HTML （10）    PDF（pc） （1109KB）（264）       Knowledge map    Save Objective To assess the value of Improved Mayo Endoscopic Score (IMES) for evaluation of treatment efficacy for active ulcerative colitis (UC). Methods We retrospectively analyzed the clinical and endoscopic data of 103 patients diagnosed with active UC in Beijing Tsinghua Changgung Hospital from January, 2015 to December, 2020. The severity of endoscopic lesions was determined by Mayo Endoscopic Score and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS), and the area of the endoscopic lesions was evaluated based on the Montreal classification system. The IMES was established by combining the MES with the Montreal classification. Results Univariate analysis suggested that young patients (<40 years old), patients with extensive disease type (E3), patients with high endoscopic scores (MES=3, UCEIS>4, and IMES>4), and patients receiving advanced drug therapy (with systemic hormones, immunosuppressants, immunomodulators, and biological agents, etc.) had lower clinical and endoscopic remission rates. COX survival analysis showed that IMES≤4 was an independent risk factor for clinical and endoscopic remission. ROC curve indicated that the predictive value of IMSE≤4 for clinical and endoscopic remission (AUC=0.7793 and 0.7095, respectively; P<0.01) was better than that of Montreal (AUC=0.7357 and 0.6847, respectively; P<0.01), MES=2 (AUC=0.6671 and 0.5929, respectively; P<0.01), and UCEIS≤4 (AUC=0.6823 and 0.6459, respectively; P<0.01); IMES=5 had a better predictive value for patients with active UC undergoing colectomy tham E3 and MES=3. Conclusion IMES has good value in evaluating treatment efficacy for active UC. Related Articles | Metrics | Comments（0）

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Guizhi Fuling Capsule inhibits migration and induces apoptosis of human ovarian cancer cells by regulating the NF-κB signaling pathway GUO Xiaojuan, CHEN Liping, LÜ Qin, DU Ruijuan, LUO Qin, ZHANG Yang, BIAN Hua, HAN Li Journal of Southern Medical University    2023, 43 (8): 1315-1321.   DOI: 10.12122/j.issn.1673-4254.2023.08.07 Abstract （515）   HTML （20）    PDF（pc） （2200KB）（202）       Knowledge map    Save Objective To study the inhibitory effect of Guizhi Fuling Capsule (GFC) on migration of human ovarian cancer cells and explore the possible mechanism. Methods Sixty Wistar rats were randomized into 4 groups for daily gavage of saline or 4, 8, or 16 g/kg GFC suspension for 5 days to prepare blank and low-, medium- and high-dose GFC-medicated sera. Cisplatin-resistant ovarian cancer SKOV3/DDP cells were treated with these sera with nuclear factor-κB (NF-κB) inhibitor SN50 as the positive control, and the changes in migration ability and apoptosis of the cells were examined using scratch assay and flow cytometry, respectively; the changes in the mRNA and protein expressions of CDH1, CDH2, caspase 3 and NF- κB were detected using RT- qPCR and Western blotting. ATAC- seq was used to analyze the changes in expressions of CDH1, CDH2, caspase 3 and NF-κB genes in the open chromatin. Results Treatment with GFC-medicated sera dose-dependently inhibited the migration (P<0.05), increased apoptosis (P<0.01), inhibited CDH2 and NF-κB mRNA expression (P<0.05), and enhanced caspase 3 and CDH1 mRNA expressions (P<0.01) in SKOV3/DDP cells. The effects of high-dose GFC-medicated serum were comparable to those of SN50 (P>0.05), but its effect for enhancing DH1 protein expression was weaker than that of SN50 (P<0.01). GFC-medicated sera significantly lowered the expressions of NF-κB and CDH2 and increased CDH1 expression in the open chromatin without obviously affecting caspase 3 expression. Conclusion GFC- medicated sera inhibits the migration ability of SKOV3/DDP cells possibly by promoting cell apoptosis and caspase 3 and CDH1 expressions, inhibiting CDH2 and NF-κB expressions, and regulating the expressions of NF-κB, CDH2 and CDH1 in the open chromatin. Related Articles | Metrics | Comments（0）

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Erchen Decoction improves iron homeostasis in mice with non-alcoholic fatty liver disease by regulating iron transport capacity in the spleen DENG Guanghui, JIA Hui, LI Yunjia, LI Junjie, WU Chaofeng, SHI Hao, QIN Mengchen, ZHAO Jiamin, LIU Chang, LIAO Yuxin, GAO Lei Journal of Southern Medical University    2023, 43 (8): 1287-1296.   DOI: 10.12122/j.issn.1673-4254.2023.08.04 Abstract （489）   HTML （15）    PDF（pc） （3455KB）（262）       Knowledge map    Save Objective To investigate the effect of Erchen Decoction on iron homeostasis in mice with nonalcoholic fatty liver disease (NAFLD) and its mechanism for regulating iron transport in spleen cells. Methods Thirty male C57BL/6J mice were given a high-fat diet for 12 weeks and randomized (n=6) at the 7th week for gavage (3 times a week) of drinking water (NAFLD model group), Erchen Decoction at low, medium and high doses (7.5, 15, and 30g/kg, respectively), or polyene phosphatidyl choline (PPC; 9.12 mg/kg), with another 6 mice with low-fat and low-sugar feeding as the control group. The active components of Erchen Decoction were determined by HPLC-MS. Lipid accumulation in the liver was evaluated by HE staining and Nile red staining. Prussian blue staining was used to observe iron content in the spleen. The iron ion content in the liver tissue was detected using a detection kit. The expressions of ferroportin1 (Fpn1), transferrin receptor (TfR), Steap3, HO-1, Ter-119, CD163 and CD68 were detected using Western blotting, immunohistochemistry and immunofluorescence staining. Results Medium- and high-dose Erchen Decoction partially reversed the increase of lipid accumulation in the liver of NAFLD mice and showed better lipid-lowering effect than PPC. The NAFLD mice showed significantly decreased iron ion content in the spleen with increased hepatic and serum iron contents (P<0.05), decreased TfR protein expression (P<0.05), and increased Fpn1 and Steap3 protein expressions (P<0.05), and these changes were significantly improved by the drug interventions. Erchen Decoction also improved the function of CD163 macrophages in the spleen of NAFLD mice by up-regulating the expression of HO-1 (P<0.05). Conclusion Erchen Decoction can alleviate high- fat diet-induced iron metabolism disorder by improving the iron ion transport ability of the spleen cells to delay the progression of NAFLD. Related Articles | Metrics | Comments（0）

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Acetylcorynoline relieves 2,4,6-trinitrobenesulfonic acid-induced Crohn's disease-like colitis in mice by regulating intestinal epithelial cell apoptosis LI Qingqing, HUANG Ju, SUN Yang, XU Yunhui, WANG Lian, ZHANG Xiaofeng, WANG Yueyue, GENG Zhijun, SONG Xue, ZUO Lugen, LI Jing, HU Jianguo Journal of Southern Medical University    2023, 43 (8): 1306-1314.   DOI: 10.12122/j.issn.1673-4254.2023.08.06 Abstract （488）   HTML （14）    PDF（pc） （2252KB）（197）       Knowledge map    Save 克罗恩病；乙酰紫堇灵；肠上皮细胞凋亡；PI3K/AKT Related Articles | Metrics | Comments（0）

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TMEM64 is highly expressed in hepatocellular carcinoma and promotes tumor cell proliferation and invasion CAO Danping, CAI Juan, LI Yanna, DONG Runyu, WANG Zhixiong, ZUO Xueliang Journal of Southern Medical University    2023, 43 (8): 1345-1355.   DOI: 10.12122/j.issn.1673-4254.2023.08.11 Abstract （476）   HTML （20）    PDF（pc） （2864KB）（205）       Knowledge map    Save Objective To analyze the expression of TMEM64 in hepatocellular carcinoma (HCC) and investigate the effect of TMEM64 expression level on proliferation and invasion of HCC cells in vitro. Methods We analyzed the expression level of TMEM64 in HCC and adjacent tissues based on data from TCGA and GTEx databases. The prognostic value of TMEM64 for HCC patients was examined using Kaplan-Meier survival analysis and a Cox regression model, and a nomogram was constructed based on TMEM64 expression and clinical characteristics of the patients. Functional enrichment analysis was performed to explore the potential signaling pathways, and immune cell infiltration was assessed using single sample gene set enrichment analysis. We also performed cell experiment to observe the changes in proliferation, migration, and invasion in HCCLM3 cells with TMEM64 knockdown and in Huh7 cells with TMEM64 overexpression using CCK-8, EdU, colony formation, Transwell, and wound healing assays. Results The expression level of TMEM64 was significantly higher in HCC than in the adjacent tissues (P<0.05). Kaplan-Meier analysis suggested that a high expression of TMEM64 was associated with poor outcomes of the patients (P<0.05). Multivariate Cox regression analysis indicated that a high TMEM64 expression was an independent risk factor for overall survival of HCC patients (P<0.05). TMEM64 expression level was negatively correlated with the levels of immune cell infiltration by NK cells, CD8 + T cells, and plasma pDCs cells (P<0.05). GO, KEGG, and GSEA enrichment analyses showed that TMEM64 was significantly enriched with tumor invasion and metastasis pathways. The nomogram and calibration curves indicated a moderate prediction reliability of the model. In the cell experiment, TMEM64 knockdown obviously suppressed and TMEM64 overexpression markedly promoted the proliferation, migration, and invasion of HCC cells (P<0.01). Conclusion A high TMEM64 expression may serve as an independent risk factor for poor prognosis of HCC and promotes proliferation, migration, and invasion of HCC cells in vitro. Related Articles | Metrics | Comments（0）

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High expression of Circ-PALLD in heart failure is transcriptionally regulated by the transcription factor GATA4 HUANG Zhuo, ZENG Zhenyu, LI Jia, CAI Rui, HE Wenxia, HU Shuting Journal of Southern Medical University    2023, 43 (8): 1371-1378.   DOI: 10.12122/j.issn.1673-4254.2023.08.14 Abstract （470）   HTML （8）    PDF（pc） （2056KB）（316）       Knowledge map    Save Objective To determine the changes in the expression of circular RNA Circ-PALLD in heart failure and explore the biogenesis of Circ-PALLD. Methods We analyzed second-generation sequencing results of human and murine heart failure samples to identify the candidate CircRNAs. Sanger generation sequencing was performed after PCR amplification, and the sequencing results were compared to determine the reverse splicing pattern of the corresponding CircRNAs. We further examined the expressions of CircRNAs and linear RNAs in 8 patients with heart failure admitted in our hospital, and RT-qPCR was performed to detect the expression levels of Circ-PALLD and PALLD in the failing myocardium. Bioinformatic analysis was performed to predict the transcription factors that may regulate PALLD. Small interfering RNAs (siRNAs) against GATA4 were used to determine the regulatory effect of the transcription factor GATA4 on PALLD. Results Sanger sequencing and sequence alignment verified the reverse splicing of Circ-VWA8, Circ-VMP1, Circ-PRDM5, Circ-PLCL2, Circ-PALLD, Circ-NFATC3, Circ-MLIP, Circ-FAM208A, Circ-ANKIB1, and Circ-AGTPBP1, demonstrated their loop-forming nature and determined the exon arrangement of reverse splicing. Semi-quantitative PCR results showed that the expression levels of Circ-PALLD, Circ-NFATC3 and Circ-AGTPBP1 were significantly increased while the expression level of linear PALLD was significantly decreased in the myocardial tissues of heart failure patients. Bioinformatic analysis suggested that the transcription of PALLD was regulated possibly by the transcription factor GATA4. RT-qPCR showed that the expression level of Circ-PALLD was significantly increased, while PALLD expression was significantly decreased in the failing myocardium, which was consistent with the results of semi-quantitative PCR. In primary mammary rat cardiomyocytes, GATA4 knockdown resulted in lowered expressions of both Circ-PALLD and PALLD. Conclusion Circ-PALLD is highly expressed in heart failure and can be used as a novel molecular marker for chronic heart failure, and GATA4 may play important role in regulating its transcription. Circ-PALLD points a new direction for investigating the molecular mechanism of heart failure and may also serve as a potential therapeutic target for heart failure. Related Articles | Metrics | Comments（0）

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Analysis of therapeutic mechanism of Liushen Wan against colitis-associated colorectal cancer based on network pharmacology and validation in mice ZHANG Xuefang, CHEN Yanhua, LI Zongheng, SHANG Jing, YUAN Zeting, DENG Wanli, LUO Ying, HAN Na, YIN Peihao, YIN Jun Journal of Southern Medical University    2023, 43 (7): 1051-1062.   DOI: 10.12122/j.issn.1673-4254.2023.07.01 Abstract （466）   HTML （68）    PDF（pc） （3383KB）（528）       Knowledge map    Save Objective To explore the therapeutic mechanism of Liushen Wan (LSW) against colitis-associated colorectal cancer (CAC) by network pharmacology. Methods TCMSP, BATMAN-TCM, CNKI, PubMed, Genecards, OMIM, and TTD databases were used to obtain the related targets of LSW and CAC. The common targets of LSW and CAC were obtained using Venny online website. The PPI network was constructed using Cytoscape 3.8.2 to screen the core targets of LSW in the treatment of CAC. GO and KEGG enrichment analysis were conducted using DAVID database. The therapeutic effect of LSW on CAC was evaluated in a C57BL/6J mouse model of AOM/DSS-induced CAC by observing the changes in body weight, disease activity index, colon length, and size and number of the tumor. HE staining and RT-qPCR were used to analyze the effect of LSW on inflammatory mediators. Immunohistochemistry and TUNEL staining were used to evaluate the effect of LSW on the proliferation and apoptosis of AOM/DSS-treated colon tumor cells. Immunohistochemistry and Western blotting were used to detect the effects of LSW on the expression of TLR4 proteins in CAC mice. Results Network pharmacology analysis identified 69 common targets of LSW and CAC, and 33 hub targets were screened in the PPI network. KEGG pathway enrichment analysis suggested that the effect of LSW on CAC was mediated by the Toll-like receptor signaling pathway. In the mouse model of AOM/DSS-induced CAC, LSW significantly inhibited colitis-associated tumorigenesis, reduced tumor number and tumor load (P<0.05), obviously improved histopathological changes in the colon, downregulated the mRNA levels of pro-inflammatory cytokines, and inhibited the proliferation (P<0.01) and promoted apoptosis of colon tumor cells (P<0.001). LSW also significantly decreased TLR4 protein expression in the colon tissue (P<0.05). Conclusion LSW can inhibit CAC in mice possibly by regulating the expression of TLR4 to reduce intestinal inflammation, inhibit colon tumor cell proliferation and promote their apoptosis. Related Articles | Metrics | Comments（0）

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A Dual-Aware deep learning framework for identification of glioma isocitrate dehydrogenase genotype using magnetic resonance amide proton transfer modalities CHU Zhiqin, QU Yaoming, ZHONG Tao, LIANG Shujun, WEN Zhibo, ZHANG Yu Journal of Southern Medical University    2023, 43 (8): 1379-1387.   DOI: 10.12122/j.issn.1673-4254.2023.08.15 Abstract （453）   HTML （10）    PDF（pc） （1529KB）（148）       Knowledge map    Save Objective To propose a Dual-Aware deep learning framework for genotyping of isocitrate dehydrogenase (IDH) in gliomas based on magnetic resonance amide proton transfer (APT) modality data as a means to assist non-invasive diagnosis of gliomas. Methods We collected multimodal magnetic resonance imaging (MRI) imaging data of the brain from 118 cases of gliomas, including 68 wild-type and 50 mutant type cases. The delineation of the ROI of brain glioma was completed in all the cases. APT modality imaging does not require contrast agents, and its signal intensity on tumors is positively correlated with tumor malignancy, and the signal intensity on wild- type IDH is higher than that on mutant IDH. For APT modalities, tumor imaging and derived areas are morphologically variable and lack prominent edge contour characteristics compared with other modalities. Based on these characteristics, we propose the Dual-Aware framework, which introduces the Multi-Aware framework to mine multi-scale features, and the Edge Aware module mines the edge features for automatic genotype identification. Results The introduction of two types of Aware mechanisms effectively improved the identification rate of the model for glioma IDH genotyping. The accuracy and AUC for each modality data were enhanced, and the best performance was achieved on the APT modality with a prediction accuracy of 83.1% and an AUC of 0.822, suggesting its advantages and effectiveness for identifying glioma IDH genotypes. Conclusion The proposed deep learning algorithm model constructed based on the image characteristics of the APT modality is effective for glioma IDH genotyping and identification task and may potentially replace the commonly used T1CE modality to avoid contrast agent injection and achieve non- invasive IDH genotyping. Related Articles | Metrics | Comments（0）