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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 （1633）   HTML （15）    PDF（pc） （3369KB）（836）       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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GGN repeat length of the androgen receptor gene is associated with antral follicle count in Chinese women undergoing controlled ovarian stimulation Xinyan LIU, Qi FAN, Mingfen DENG, Yan XU, Jing GUO, Ping CAO, Canquan ZHOU, Yanwen XU Journal of Southern Medical University    2025, 45 (2): 213-222.   DOI: 10.12122/j.issn.1673-4254.2025.02.01 Abstract （1633）   HTML （39）    PDF（pc） （934KB）（206）       Knowledge map    Save Objective To evaluate the association of GGN repeat polymorphism of androgen receptor (AR) with ovarian reserve and ovarian response in controlled ovarian stimulation (COS). Methods This genetic association study was conducted among a total of 361 women aged ≤40 years with basal FSH≤12 U/L undergoing the GnRH-agonist long protocol for COS in a university-affiliated IVF center. GGN repeat in the AR gene was analyzed with Sanger sequencing. The primary endpoint was the number of antral follicle counts (AFCs), and the secondary endpoints were stimulation days, total dose of gonadotropin (Gn) used, total number of retrieved oocytes, ovarian sensitivity index, and follicular output rate. Results The GGN repeat in exon 1 of the AR gene ranged from 13 to 24, and the median repeat length was 22. Based on the genotypes (S for GGN repeats <22, L for GGN repeats ≥22), the patients were divided into 3 groups: SS, SL, and LL. Generalized regression analysis indicated that the number of AFCs in group SS was significantly lower than those in group SL (adjusted β=1.8, 95% CI: 0.2-3.4, P=0.024) and group LL (adjusted β=1.5, 95% CI: 0.2-2.7, P=0.021). No significant difference was observed in the number of AFCs between group SL and group LL (P>0.05). Generalized regression analysis indicated no significant differences in ovarian stimulation parameters among the 3 groups, either before or after adjusting for confounding factors (P>0.05). Conclusion GGN repeat length on the AR gene is associated with AFC but not with ovarian response in Chinese women, indicating that AR gene polymorphisms may affect ovarian reserve. Table and Figures | Reference | 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 （1514）   HTML （10）    PDF（pc） （1193KB）（653）       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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SLC1A5 overexpression accelerates progression of hepatocellular carcinoma by promoting M2 polarization of macrophages Jinhua ZOU, Hui WANG, Dongyan ZHANG Journal of Southern Medical University    2025, 45 (2): 269-284.   DOI: 10.12122/j.issn.1673-4254.2025.02.08 Abstract （1487）   HTML （11）    PDF（pc） （8201KB）（114）       Knowledge map    Save Objective To investigate the clinical significance of SLC1A5 overexpression in pan-cancer and its mechanism for promoting hepatocellular carcinoma (HCC) progression. Methods We analyzed the correlation of SLC1A5 expression with clinical stage, lymph node metastasis and prognosis in pan-cancer using TCGA and ICGC datasets and explored its association with immune cell infiltration using EPIC, CIBERSORT, and TIMER algorithms. In HCC cell lines, the effects of lentivirus-mediated SLC1A5 overexpression or RNA interference on cell proliferation were examined using CCK-8 assay, and the growth of HCC cell xenografts overexpressing SLC1A5 was observed in nude mice. The effects of SLC1A5 overexpression or silencing in HCC cells on macrophage polarization were evaluated in a cell co-culture system. Results SLC1A5 was mainly localized on cell membrane and was highly expressed in most cancers in association with clinical stage, lymph node metastasis and poor prognosis. SLC1A5 expression was positively correlated with immunity score in 13 cancer types, especially in low-grade glioma (LGG), LIHC and thyroid cancer. SLC1A5 was positively correlated with macrophage infiltration level in LGG and LIHC but negatively correlated with macrophage infiltration in 5 cancers including lung squamous carcinoma, pancreatic carcinoma, and gastric carcinoma. Patients with SLC1A5 overexpression and high level of M2 macrophage infiltration had the worst survival outcomes. SLC1A5 was correlated with immunosuppression-related genes, cytokines, and cytokine receptors, which was the most obvious in LGG and LIHC. SLC1A5 was highly expressed in different HCC cell lines, and its overexpression promoted HCC cell proliferation both in vitro and in nude mice. In the cell co-culture experiment, SLC1A5 was positively correlated with the molecular markers of M2 polarization of macrophages, and its overexpression strongly promoted M2 polarization of the macrophages and inhibited T cell secretion of IFN-γ. Conclusion SLC1A5 expression level is correlated with clinical stage, lymph node metastasis, prognosis, and immune cell infiltration in most cancers, and its overexpression promotes HCC progression by inhibiting T-cell function via promoting M2 polarization of macrophages. Table and Figures | Reference | Related Articles | Metrics | Comments（0）

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Biological role of SPAG5 in the malignant proliferation of gastric cancer cells Yidan PANG, Ya LIU, Siai CHEN, Jinglei ZHANG, Jin ZENG, Yuanming PAN, Juan AN Journal of Southern Medical University    2024, 44 (8): 1497-1507.   DOI: 10.12122/j.issn.1673-4254.2024.08.08 Abstract （1461）   HTML （19）    PDF（pc） （9843KB）（341）       Knowledge map    Save Objective To analyze the expression of SPAG5 in gastric cancer tissues and its regulatory roles in gastric cancer cell growth. Methods TCGA analysis, immunohistochemistry, and immunofluorescence staining were used to analyze the expression patterns of SPAG5 and MKi67 in gastric cancer and adjacent tissues. In gastric cancer AGS and MGC803 cells, the effects of lentivirus-mediated SPAG5 knockdown on cell growth and apoptosis were evaluated using Celigo, MTT, clone formation assays and flow cytometry. Results Proteinatlas and TCGA database analysis suggested that SPAG5 was highly expressed in gastric cancer, and Kaplan-Meier analysis and GEPIA analysis showed high expressions of SPAG 5 in lung adenocarcinoma, breast cancer, hepatocellular carcinoma, pancreatic carcinoma, cervical cancer and bladder carcinoma. Immunohistochemistry revealed that SPAG5 was highly expressed in gastric cancer tissues (P<0.001), and immunofluorescence colocalization analysis demonstrated a significant correlation between SPAG5 and MKI67 (R=0.393, P<0.001). RT-qPCR and Western blotting showed that SPAG5 was highly expressed in MKN74, BGC823, MGC803, SGC7901 and AGS cells. In AGS and MGC803 cells, SPAG5 knockdown significantly inhibited proliferation and promoted apoptosis. Conclusions The expressions of SPAG5 and MKi67 are correlated in gastric cancer tissues, and SPAG5 knockdown inhibits the proliferation of gastric cancer cells. SPAG5 is associated with the prognosis of gastric cancer patients and may serve as a promising biomarker for gastric cancer. Table and Figures | Reference | 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 （1417）   HTML （17）    PDF（pc） （2616KB）（307）       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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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 （1404）   HTML （9）    PDF（pc） （883KB）（409）       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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Exocarpium Citri Grandis formula granules alleviate fatty liver disease in Zebrafish by maintaining iron homeostasis and suppressing lipid peroxidation and ferroptosis Yuxue ZAHNG, Jieying LAN, Xinyi MA, Qiong ZHOU, Mengchen QIN, Lei GAO Journal of Southern Medical University    2024, 44 (12): 2265-2275.   DOI: 10.12122/j.issn.1673-4254.2024.12.01 Abstract （1403）   HTML （57）    PDF（pc） （9786KB）（746）       Knowledge map    Save Objective To investigate the therapeutic effect of Exocarpium Citri Grandis formula granules (ECGFG) on fatty liver disease (FLD) in zebrafish and explore the underlying mechanism. Methods Nonalcoholic fatty liver disease (NAFLD) and alcoholic fatty liver disease (ALD) models were established in zebrafish larvae at 3 days post fertilization (dpf), in which the treatment efficacy of 16, 32, or 64 μg/mL ECGFG was evaluated by examining zebrafish survival and liver pathologies and using whole-fish oil red O staining and RT-qPCR. The therapeutic mechanism of ECGFG for FLD was investigated using Prussian blue staining, DCFH-DA probe, MDA content detection, RT-qPCR assay and immunohistochemical staining for CAV1. Results In zebrafish models of NAFLD and ALD, treatment with ECGFG significantly reduced lipid accumulation and the expression levels of FASN, SREBP1, HMGCRA, TNF-α and IL-6, increased the expressions of Apoa1 and PPARα, and reduced iron deposition and the contents of MDA and ROS in the liver. In zebrafish models of NAFLD, treatment with ECGFG at the 3 doses significantly increased hepatic expressions of Tf, TfR, FPN and SLC7A11, and at the doses of 32 and 64 μg/mL, ECGFG obviously increased hepatic expression of GPX4. ALD fish models showed significantly increased hepatic expressions of Tf, TfR and FPN, which were effectively lowered by treatment with ECGFG at the 3 doses. ECGFG did not obviously affect the expression of SLC7A11, but its high dose (64 μg/mL) caused significant elevation of GPX4 expression. Both zebrafish models of NAFLD and ALD showed obviously increased CAV1 expression level in the liver, which was significantly reduced by treatment with 32 and 64 μg/mL ECGFG. Conclusion In zebrafish models of NAFLD and ALD, ECGFG can alleviate lipid accumulation and inflammatory response and lower the expression level of CAV1 to restore iron homeostasis and suppress lipid peroxidation and ferroptosis in the liver. Table and Figures | Reference | Related Articles | Metrics | Comments（0）

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Low-intensity pulsed ultrasound combined with nystatin treatment synergistically inhibits vaginal Candida albicans biofilm infection in rabbits Mengyao XIE, Min YANG, Xin LI, Yonghong DU Journal of Southern Medical University    2025, 45 (2): 296-303.   DOI: 10.12122/j.issn.1673-4254.2025.02.10 Abstract （1394）   HTML （3）    PDF（pc） （3346KB）（81）       Knowledge map    Save Objective To explore the efficacy of low-intensity pulsed ultrasound (LIPUS) combined with nystatin for treatment of vaginal Candida albicans biofilm infection. Methods In vitro cultured Candida albicans biofilm were treated with LIPUS, nystatin, or both, and the minimum inhibitory concentration (MIC) of nystatin was determined. Crystal violet staining, confocal laser microscopy (CLSM) and scanning electron microscopy were used to quantify the biofilm and observe the activity and morphological changes of the biofilms; DCFH-DA was used to detect the changes in reactive oxygen species (ROS). Twenty female New Zealand White rabbits with vaginal inoculation of Candida albicans biofilm were randomized into 4 groups for treatment with normal saline, LIPUS, nystatin, or both LIPUS and nystatin. The changes in vulvar symptoms of the rabbits were observed, and the histopathological and ultrastructural changes of the vagina before and after treatment were observed using HE staining and transmission electron microscopy. Results In the combined treatment group, the MIC50 and MIC80 of nystatin in Candida albicans biofilms were both reduced by 50% compared with those in nystatin group, and the biofilm clearance rate increased by 26% and 68% compared with nystatin and LIPUS groups, respectively. Compared with nystatin and LIPUS treatment alone, the combined treatment produced stronger effects for inhibiting biofilm activity, causing structural disruption and promoting ROS production. In the rabbit models, the combined treatment more effectively improved vulvar symptoms and inflammatory infiltration, reduced residual vaginal hyphae/strains, and improved ultrastructure of the vaginal epithelium than LIPUS and nystatin treatment alone. Conclusion LIPUS combined with nystatin produces a significant synergistic antifungal effect against Candida albicans biofilm both in vitro and in vivo. Table and Figures | Reference | Related Articles | Metrics | Comments（0）

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Pharmacodynamics of Qingxin Jieyu Granules for treatment of atherosclerosis and its regulatory mechanism for lipid metabolism Shanyuan ZHANG, Qiaoyan CAI, Jianghan QI, Kaixin YIN, Chenchen HE, Zhuye GAO, Ling ZHANG, Jianfeng CHU Journal of Southern Medical University    2024, 44 (8): 1518-1528.   DOI: 10.12122/j.issn.1673-4254.2024.08.10 Abstract （1390）   HTML （4）    PDF（pc） （10066KB）（426）       Knowledge map    Save Objective To elucidate the therapeutic mechanism of Qingxin Jieyu Granule (QXJYG) against atherosclerosis (AS) based on network pharmacology. Methods The major targets and pathways of QXJYG against AS were analyzed using network pharmacology. Rat models of AS established by high-fat feeding combined with intraperitoneal vitamin D3 injection were treated daily with normal saline, atorvastatin (13.15 mg/kg), or QXJYG at 0.99, 1.98, and 3.96 g/kg for 8 weeks (n=6). Ultrasound and HE staining were used to assess the function and pathologies of the abdominal aorta. Blood lipids and serum levels of Ang II, ET-1, TXA2, PGI2, and ox-LDL of the rats were detected using an automatic biochemical analyzer or ELISA. The expressions of LOX-1, PPARγ, RXRα, p-P65, VCAM-1 and ICAM-1 in the abdominal aorta were detected with immunohistochemistry. Results The rat models of AS showed obvious abdominal aorta wall thickening, increased pulse wave velocity and pulse index, decreased inner diameter of the abdominal aorta, elevated levels of TC, LDL-C, Ang II, ET-1 and TXA2, and lowered levels of HDL-C and PGI2. QXJYG and atorvastatin treatment of the rat models significantly alleviated histopathological changes of the abdominal aorta, decreased serum levels of TC, LDL-C, Ang II, ET-1 and TXA2, and increased the levels of HDL-C and PGI2. Network pharmacology study suggested the therapeutic effect of QXJYG against AS was mediated by regulating lipid metabolism, PPAR and NF‑κB pathways. Consistently, treatments with QXJYG were found to significantly decrease ox-LDL level and LOX-1, P-P65, VCAM-1 and ICAM-1 protein expressions while increasing PPARγ and RXRα expressions in the aorta of AS rats. Conclusion QXJYG alleviates lipid metabolism disorder and improves histopathological changes of the abdominal aorta of AS rats possibly by lowering ox-LDL level, reducing LOX-1 expression, activating PPARγ and RXRα, and inhibiting P65 phosphorylation to reduce VCAM-1 and ICAM-1 expression in the aorta. Table and Figures | Reference | Related Articles | Metrics | Comments（0）

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Prediction of microvascular invasion in hepatocellular carcinoma with magnetic resonance imaging using models combining deep attention mechanism with clinical features GONG Gao, CAO Shi, XIAO Hui, FANG Weiyang, QUE Yuqing, LIU Ziwei, CHEN Chaomin Journal of Southern Medical University    2023, 43 (5): 839-851.   DOI: 10.12122/j.issn.1673-4254.2023.05.21 Abstract （1355）   HTML （16）    PDF（pc） （2775KB）（545）       Knowledge map    Save Objective To investigate the consistency and diagnostic performance of magnetic resonance imaging (MRI) for detecting microvascular invasion (MVI) of hepatocellular carcinoma (HCC) and the validity of deep learning attention mechanisms and clinical features for MVI grade prediction. Methods This retrospective study was conducted among 158 patients with HCC treated in Shunde Hospital Affiliated to Southern Medical University between January, 2017 and February, 2020. The imaging data and clinical data of the patients were collected to establish single sequence deep learning models and fusion models based on the EfficientNetB0 and attention modules. The imaging data included conventional MRI sequences (T1WI, T2WI, and DWI), enhanced MRI sequences (AP, PP, EP, and HBP) and synthesized MRI sequences (T1mapping-pre and T1mapping-20 min), and the high-risk areas of MVI were visualized using deep learning visualization techniques. Results The fusion model based on T1mapping-20min sequence and clinical features outperformed other fusion models with an accuracy of 0.8376, a sensitivity of 0.8378, a specificity of 0.8702, and an AUC of 0.8501 for detecting MVI. The deep fusion models were also capable of displaying the high- risk areas of MVI. Conclusion The fusion models based on multiple MRI sequences can effectively detect MVI in patients with HCC, demonstrating the validity of deep learning algorithm that combines attention mechanism and clinical features for MVI grade prediction. 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 （1344）   HTML （14）    PDF（pc） （2472KB）（564）       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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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 （1292）   HTML （33）    PDF（pc） （1023KB）（530）       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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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 （1291）   HTML （18）    PDF（pc） （4146KB）（1441）       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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Ag2Se nanoparticles suppress growth of murine esophageal cancer allograft in mice by eliminating Porphyromonas gingivalis Yali ZHAO, Jiayi LI, Bianli GU, Pan CHEN, Li ZHANG, Xiaoman ZHANG, Pingjuan YANG, Linlin SHI, Shegan GAO Journal of Southern Medical University    2025, 45 (2): 245-253.   DOI: 10.12122/j.issn.1673-4254.2025.02.05 Abstract （1289）   HTML （5）    PDF（pc） （15333KB）（75）       Knowledge map    Save Objectives To investigate the efficacy of Ag2Se nanoparticles for eliminating intracellular Porphyromonas gingivalis (P. gingivalis) in esophageal cancer and examine the effect of P. gingivalis clearance on progression of esophageal cancer. Methods Ag2Se nanoparticles were synthesized via a chemical synthesis method. The effects of Ag2Se nanoparticles on P. gingivalis viability and colony-forming ability were assessed using fluorescence staining and colony formation assays. In a mouse model bearing subcutaneous murine esophageal cancer cell allograft with P. gingivalis infection, the effect of treatment with Ag2Se nanoparticles on the abundance of P. gingivalis in the tumor tissues was quantified using RNAscope in situ hybridization and quantitative polymerase chain reaction (qPCR), and the changes in tumor volume were monitored. The biosafety of Ag2Se nanoparticles was assessed by examining liver and kidney functions and pathological changes in the major organs of the mice. Results Transmission electron microscopy revealed that the synthesized Ag2Se nanoparticles were uniformly dispersed spherical particles with a diameter around 50 nm. In vitro experiments demonstrated that exposure to Ag2Se nanoparticles significantly reduced the viability and clonal proliferation capacity of P. gingivalis in a dose-dependent manner. In the tumor-bearing mice, treatment with Ag2Se nanoparticles significantly reduced the abundance of P. gingivalis in tumor tissues and suppressed tumor cell proliferation. No significant damages to the liver and kidney functions or the major organs were observed in Ag2Se nanoparticle-treated mice, demonstrating good biocompatibility of Ag2Se nanoparticles. Conclusion Ag2Se nanoparticles exhibit significant bactericidal and inhibitory effects against P. gingivalis, and can effectively eliminate intracellular P. gingivalis to suppress the growth of esophageal cancer allograft in mice, suggesting the potential of Ag2Se nanoparticles in the treatment of esophageal cancer. Table and Figures | Reference | Related Articles | Metrics | Comments（0）

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Activation of GABAergic neurons in the zona incerta accelerates anesthesia induction with sevoflurane and propofol without affecting anesthesia maintenance or awakening in mice CAO Fuyang, GUO Yongxin, GUO Shuting, ZHOU Zhikang, CAO Jiangbei, TONG Li, MI Weidong Journal of Southern Medical University    2023, 43 (5): 718-726.   DOI: 10.12122/j.issn.1673-4254.2023.05.06 Abstract （1273）   HTML （27）    PDF（pc） （3997KB）（431）       Knowledge map    Save Objective To explore the regulatory effects of GABAergic neurons in the zona incerta (ZI) on sevoflurane and propofol anesthesia. Methods Forty-eight male C57BL/6J mice divided into 8 groups (n=6) were used in this study. In the study of sevoflurane anesthesia, chemogenetic experiment was performed in 2 groups of mice with injection of either adeno-associated virus carrying hM3Dq (hM3Dq group) or a virus carrying only mCherry (mCherry group). The optogenetic experiment was performed in another two groups of mice injected with an adeno-associated virus carrying ChR2 (ChR2 group) or GFP only (GFP group). The same experiments were also performed in mice for studying propofol anesthesia. Chemogenetics or optogenetics were used to induce the activation of GABAergic neurons in the ZI, and their regulatory effects on anesthesia induction and arousal with sevoflurane and propofol were observed; EEG monitoring was used to observe the changes in sevoflurane anesthesia maintenance after activation of the GABAergic neurons. Results In sevoflurane anesthesia, the induction time of anesthesia was significantly shorter in hM3Dq group than in mCherry group (P<0.05), and also shorter in ChR2 group than in GFP group (P<0.01), but no significant difference was found in the awakening time between the two groups in either chemogenetic or optogenetic tests. Similar results were observed in chemogenetic and optogenetic experiments with propofol (P<0.05 or 0.01). Photogenetic activation of the GABAergic neurons in the ZI did not cause significant changes in EEG spectrum during sevoflurane anesthesia maintenance. Conclusion Activation of the GABAergic neurons in the ZI promotes anesthesia induction of sevoflurane and propofol but does not affect anesthesia maintenance or awakening. Related Articles | Metrics | Comments（0）

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Advanced Faster RCNN: a non-contrast CT-based algorithm for detecting pancreatic lesions in multiple disease stages LIANG Lidu, ZHANG Haojie, LU Qian, ZHOU Chenjie, LI Shulong Journal of Southern Medical University    2023, 43 (5): 755-763.   DOI: 10.12122/j.issn.1673-4254.2023.05.11 Abstract （1250）   HTML （19）    PDF（pc） （1773KB）（307）       Knowledge map    Save Objective To propose a non-contrast CT-based algorithm for automated and accurate detection of pancreatic lesions at a low cost. Methods With Faster RCNN as the benchmark model, an advanced Faster RCNN (aFaster RCNN) model for pancreatic lesions detection based on plain CT was constructed. The model uses the residual connection network Resnet50 as the feature extraction module to extract the deep image features of pancreatic lesions. According to the morphology of pancreatic lesions, 9 anchor frame sizes were redesigned to construct the RPN module. A new Bounding Box regression loss function was proposed to constrain the training process of RPN module regression subnetwork by comprehensively considering the constraints of the lesion shape and anatomical structure. Finally, a detection frame was generated using the detector in the second stage. The data from a total of 728 cases of pancreatic diseases from 4 clinical centers in China were used for training (518 cases, 71.15%) and testing (210 cases, 28.85%) of the model. The performance of aFaster RCNN was verified through ablation experiments and comparison experiments with 3 classical target detection models SSD, YOLO and CenterNet. Results The aFaster RCNN model for pancreatic lesion detection achieved recall rates of 73.64% at the image level and 92.38% at the patient level, with an average precision of 45.29% and 53.80% at the image and patient levels, respectively, which were higher than those of the 3 models for comparison. Conclusion The proposed method can effectively extract the imaging features of pancreatic lesions from non-contrast CT images to detect the pancreatic lesions. Related Articles | Metrics | Comments（0）

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Thesium chinense Turcz. alleviates antibiotic-associated diarrhea in mice by modulating gut microbiota structure and regulating the EGFR/PI3K/Akt signaling pathway Haonan¹ XU, Fang³ ZHANG, Yuying² HUANG, Qisheng⁴ YAO, Yueqin⁴ GUAN, Hao CHEN Journal of Southern Medical University    2025, 45 (2): 285-295.   DOI: 10.12122/j.issn.1673-4254.2025.02.09 Abstract （1237）   HTML （7）    PDF（pc） （5812KB）（104）       Knowledge map    Save Objective To investigate the therapeutic mechanism of Thesium chinense Turcz. (TCT) for antibiotic-associated diarrhea (AAD). Methods Network pharmacology, KEGG pathway enrichment analysis and molecular docking were used to identify the shared targets and genes of TCT and AAD, the key signaling pathways and the binding between the active components in TCT and the core protein targets. In a Kunming mouse model of AAD established by intragastric administration of lincomycin hydrochloride, the effects of daily gavage of 1% carboxymethyl cellulose sodium or TCT gel solutions at 1.5 g/kg and 3 g/kg (n=10) on body weight and diarrhea were observed. HE staining, ELISA, 16S rRNA sequencing, and Western blotting were used to examine pathologies, expression levels of IL-6 and TNF-α, changes in gut microbiota, and protein expressions of EGFR, p-EGFR, PI3K, p-PI3K, Akt, and p-Akt in the colon tissues of the mice. Results We identified a total of 66 active components of TCT and 68 core targets including EGFR, STAT3 and PIK3CA. KEGG pathway enrichment analysis suggested that the therapeutic effects of TCT was mediated primarily through the PI3K/Akt signaling pathway. Molecular docking showed that EGFR had the highest binding affinity with coniferin, and the EGFR-coniferin complex maintained a stable conformation at 10 ns, whose stability was also confirmed by Gibbs free energy analysis. In the mouse models of AAD, treatment with TCT significantly improved colonic tissue morphology, decreased colonic levels of TNF-α and IL-6, increased gut microbiota diversity, and modulated the relative abundances of the key genera including Lactobacillus and Bacteroides. TCT treatment also markedly reduced protein expressions of p-EGFR, p-PI3K and p-Akt in the colon tissues of the mice. Conclusion TCT can alleviate AAD in mice by modulating gut microbiota composition, regulating the EGFR/PI3K/Akt signaling pathway, and reducing TNF‑α and IL-6 expressions. Table and Figures | Reference | Related Articles | Metrics | Comments（0）

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Electroacupuncture improves learning and memory function and promotes hippocampal synaptic regeneration in rats with cerebral ischemia-reperfusion injury Ruhui LIN, Jinyan XIA, Xiaohan MA, Zuanfang LI Journal of Southern Medical University    2024, 44 (12): 2317-2326.   DOI: 10.12122/j.issn.1673-4254.2024.12.07 Abstract （1210）   HTML （6）    PDF（pc） （2267KB）（371）       Knowledge map    Save Objective To explore the neuroprotective mechanism of electroacupuncture at the acupoints Baihui and Shenting in rats with cerebral ischemia-reperfusion (IR) injury. Methods Forty-eight male SD rats were equally randomized into sham operation group, cerebral IR model group, acupoint electroacupuncture group and non-acupoint acupuncture group. In the latter 3 groups, cerebral focal ischemic injury was induced using the Longa method; in the two electroacupuncture groups, electroacupuncture was performed either at the acupoints Baihui and Shenting or at non-acupoint sites for 7 days. The changes in neurological deficit scores, cerebral infarction volume, learning and memory function, pathologies in hippocampal CA1 area, neuronal and synaptic ultrastructures, and synaptic density of the rats were observed, and serum GABA level and mRNA and protein expressions of GABAAR α1, CaMK II, SYN1 and PSD-95 in the hippocampal tissue were detected. Results Compared with those in cerebral IR model group, the rats receiving electroacupuncture at the acupoints, but not those with electroacupuncture at the non-acupoints, showed significantly decreased neurological deficit scores and cerebral infarction volume with shortened escape latency and increased platform crossings. Electroacupuncture at the acupoints significantly increased neuronal cell number, decreased the width of the synaptic gaps and increased density of synaptic bodies in the ischemic hippocampal CA1 area, resulting also in increased serum GABA levels and hippocampal expressions of GABAARα1, SYN1 and PSD-95 and lowered expression level of CaMK II. Conclusion Electroacupuncture at Baihui and Shenting improves learning and memory function of rats with cerebral IR injury possibly through a mechanism that promotes synaptic regeneration, upregulates hippocampal expressions of GABAAR α 1, SYN1 and PSD-95 and downregulates the expression of CaMK II. Table and Figures | Reference | Related Articles | Metrics | Comments（0）

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A region-level contrastive learning-based deep model for glomerular ultrastructure segmentation on electron microscope images LIN Guoyu, ZHANG Zhentai, LU Yanmeng, GENG Jian, ZHOU Zhitao, LU Lijun, CAO Lei Journal of Southern Medical University    2023, 43 (5): 815-824.   DOI: 10.12122/j.issn.1673-4254.2023.05.18 Abstract （1207）   HTML （22）    PDF（pc） （2543KB）（529）       Knowledge map    Save Objective We propose a novel region-level self-supervised contrastive learning method USRegCon (ultrastructural region contrast) based on the semantic similarity of ultrastructures to improve the performance of the model for glomerular ultrastructure segmentation on electron microscope images. Methods USRegCon used a large amount of unlabeled data for pre- training of the model in 3 steps: (1) The model encoded and decoded the ultrastructural information in the image and adaptively divided the image into multiple regions based on the semantic similarity of the ultrastructures; (2) Based on the divided regions, the first-order grayscale region representations and deep semantic region representations of each region were extracted by region pooling operation; (3) For the first-order grayscale region representations, a grayscale loss function was proposed to minimize the grayscale difference within regions and maximize the difference between regions. For deep semantic region representations, a semantic loss function was introduced to maximize the similarity of positive region pairs and the difference of negative region pairs in the representation space. These two loss functions were jointly used for pre-training of the model. Results In the segmentation task for 3 ultrastructures of the glomerular filtration barrier based on the private dataset GlomEM, USRegCon achieved promising segmentation results for basement membrane, endothelial cells, and podocytes, with Dice coefficients of (85.69 ± 0.13)% , (74.59 ± 0.13)% , and (78.57 ± 0.16)% , respectively, demonstrating a good performance of the model superior to many existing image-level, pixel-level, and region-level self-supervised contrastive learning methods and close to the fully- supervised pre-training method based on the large- scale labeled dataset ImageNet. Conclusion USRegCon facilitates the model to learn beneficial region representations from large amounts of unlabeled data to overcome the scarcity of labeled data and improves the deep model performance for glomerular ultrastructure recognition and boundary segmentation. Related Articles | Metrics | Comments（0）