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Jiangtang Sanhuang tablet inhibits endoplasmic reticulum stress and autophagy in diabetic mouse islet cells ZHANG Wenjing, HU Zhaoting Journal of Southern Medical University    2022, 42 (9): 1317-1323.   DOI: 10.12122/j.issn.1673-4254.2022.09.07 Abstract （6006）   HTML （45）    PDF（pc） （1911KB）（428）       Knowledge map    Save Objective To investigate effects of Jiangtang Sanhuang tablet (JTSHT) for regulating blood glucose and alleviating islet cell damage in db/db mice and its protective effects against endoplasmic reticulum stress (ERS) and autophagy induced by glycolipid toxicity. Methods Forty db/db mice were randomized into 4 groups for daily intragastric administration of saline, JTSHT of 2.64 and 1.32 g/kg, and metformin at 0.225g/kg for 8 weeks, using 10 C57BL/6J mice as the normal control. After the treatments, the metabolic indexes of the mice were measured, and morphological changes of the islet cells were observed. A mouse islet cell line (MIN6) was exposed to high glucose (22 mmol/L glucose) and 0.1 mmol/L palmitic acid, followed by treatment with the sera from JTSHT- or saline- treated SD rats, alone or in combination with SP600125, and the changes in cell apoptosis, ERS and autophagy were evaluated using flow cytometry, RT-qPCR and Western blotting. Results In db/db mice, treatment with JTSHT significantly improved glucose and lipid metabolism (P<0.05) and suppressed progressive weight gain (P<0.05) without significant effect on drinking water volume (P>0.05). JTSHT was also found to promote repair of islet cell injuries. In the cell experiments, high glucose exposure significantly increased apoptosis rate of MIN6 cells (P<0.05), which was obviously lowered by treatment with JTSHT-treated rat serum (P<0.05). Western blotting showed that JTSHT significantly reduced the level of ERS and autophagy caused by glycolipid toxicity in MIN6 cells (P<0.05). Interference with ERS using SP600125 significantly attenuated the protective effect of JTSHT against MIN6 cell injury, apoptosis and autophagy induced by glycolipid toxicity (P<0.05). Conclusion JTSHT has protective effects against glycolipid toxicity in MIN6 cells possibly by inhibiting ERS and autophagy. Related Articles | Metrics | Comments（0）

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Improved Mayo Endoscopic Score has a higher value for evaluating clinical severity of ulcerative colitis SONG Zejun, ZHANG Mingjun, REN Yutang, JIANG Bo Journal of Southern Medical University    2022, 42 (7): 997-1005.   DOI: 10.12122/j.issn.1673-4254.2022.07.05 Abstract （3739）   HTML （43）    PDF（pc） （1016KB）（367）       Knowledge map    Save Objective To assess the value of Improved Mayo Endoscopic Score (IMES) for evaluation of the clinical severity of ulcerative colitis (UC). Methods We retrospectively analyzed the clinical and endoscopic data of 167 patients diagnosed with UC in Beijing Tsinghua Changgung Hospital from January, 2015 to November, 2021. The severity of endoscopic lesions was determined by Mayo Endoscopic Score (MES, 0-3 points) and the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score (0-8 points), and the scope of endoscopic lesions was evaluated based on the Montreal classification system. The IMES was established by combining the MES with the Montreal classification. Results The IMSE showed stronger correlations with modified Truelove and Witts Disease Severity, Mayo score and partial Mayo score (r=0.712, 0.784, and 0.703, respectively) than MES (r=0.642, 0.754, and 0.604, respectively), Montreal classification (r=0.598, 0.628, and 0.603, respectively) and UCEIS (r= 0.670, 0.767, and 0.677, respectively). ROC curve analysis showed that IMES was superior to MES, Montreal and UCEIS in diagnosis of severe and moderate- to-severe UC. IMES also showed stronger correlations with the laboratory indicators including CRP (r=0.583), WBC (r=0.235), HB (r=-0.280), PLT (r=0.352), ALB (r=-0.396) and ESR (r=0.471) than MES and Montreal classification. An IMES score of 5 was of greater value than a MES score of 3, E3, and UCEIS≥6 for predicting the administration of systemic hormones, immunosuppressants, or surgery in the near future. Conclusion IMES can better reflect the clinical severity of UC and has good correlations with the laboratory indicators of the patients. Related Articles | Metrics | Comments（0）

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Genetic testing and analysis of 2 cases of trisomy 11 mosaicism XIE Xiaoxiao, ZHAO Qingdong, FU Yurong, ZHANG Wenling, MENG Yuanguang, LU Yanping Journal of Southern Medical University    2022, 42 (7): 1057-1061.   DOI: 10.12122/j.issn.1673-4254.2022.07.14 Abstract （1849）   HTML （28）    PDF（pc） （1097KB）（382）       Knowledge map    Save Trisomy 11 mosaicism is clinically rare, for which making diagnostic and treatment decisions can be challenging. In this study, we used noninvasive prenatal testing, chromosome karyotype analysis, chromosome microarray analysis, copy number variation sequencing and fluorescence in situ hybridization for detecting trisomy 11 mosaicism in two cases and provided them with genetic counseling. In one of the cases, the fetus with confined placental mosaicism trisomy 11 presented with severe growth restriction and a placental mosaic level of 44%, and pregnancy was terminated at 25+3 weeks of gestation. In the other case with true low-level fetal mosaicism of trisomy 11, the pregnancy continued after exclusion of the possibility of uniparental disomy and structural abnormalities and careful prenatal counseling. The newborn was followed up for more than one year, and no abnormality was found. Noninvasive prenatal testing is capable of detecting chromosomal mosaicism but may cause missed diagnosis of true fetal mosaicism. For cases with positive noninvasive prenatal testing but a normal karyotype of the fetus, care should be taken in prenatal counseling and pregnancy management. Related Articles | Metrics | Comments（0）

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Cold stress reduces lifespan and mobility of C. elegans by mediating lipid metabolism disorder and abnormal stress response SHI Hao, ZHANG Chao, ZHAO Jiamin, LI Yiwen, LI Yunjia, LI Junjie, ZENG Zhiyun, GAO Lei Journal of Southern Medical University    2022, 42 (8): 1159-1165.   DOI: 10.12122/j.issn.1673-4254.2022.08.07 Abstract （1781）   HTML （48）    PDF（pc） （1178KB）（677）       Knowledge map    Save Objective To investigate the changes of lipid metabolism and stress response of adult C. elegans exposed to non-freezing low temperature and explore the possible mechanism. Methods The survival rate and activity of adult C. elegans cultured at 20 ℃ or 4 ℃ were observed. Lipid metabolism of the cultured adult C. elegans was evaluated using oil red O staining and by detecting the expressions of the genes related with lipid metabolism. The effects of low temperature exposure on stress level of adult C. elegans were evaluated using mitochondrial fluorescence staining and by detecting the expression levels of stress-related genes and antioxidant genes at both the mRNA and protein levels. Results The lifespan and activity of adult C. elegans exposed to low temperature were significantly reduced with decreased lipid accumulation (P<0.05) and decreased expressions of genes related with fatty acid synthesis and metabolism (fat-5, fat-6, fat-7, fasn-1, nhr-49, acs-2 and aco-1; P<0.01). Cold stress significantly increased the expressions of heat shock proteins hsp-70 and hsp16.2 (P<0.05) but lowered the number of mitochondria (P<0.0001) and the expressions of atfs-1, sod-2, sod-3 and gpx-1 (P<0.05). Knockout of fat-5, nhr-49 or both fat-5 and fat-6 obviously enhanced the sensitivity of C. elegans to cold stress as shown by further reduced activity (P<0.05) and reduced survival rate at 24 h (P<0.0001) under cold stress. Conclusion Exposure to a low temperature at 4 ℃ results in lowered lipid metabolism of adult C. elegans accompanied by a decreased mitochondrial number and quality control ability, which triggers high expressions of stress-related genes and causes reduction of antioxidant capacity, thus callsing lowered activity and reduced lifespan of C. elegans. Related Articles | Metrics | Comments（0）

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E.faecium QH06 alleviates TNBS-induced colonic mucosal injury in rats KUERBANNAIMU Kaheman, ZHAO Jianfeng, MUKAIDAISI Aihemaiti, WANG Hanming, ZHU Jiwei, PAN Wentao, KASIMUJIANG Aximujiang Journal of Southern Medical University    2022, 42 (7): 976-987.   DOI: 10.12122/j.issn.1673-4254.2022.07.03 Abstract （1725）   HTML （39）    PDF（pc） （2364KB）（504）       Knowledge map    Save Objective To investigate the effect of Enterococcus faecium QH06 on TNBS-induced ulcerative colitis (UC) in rats and explore the mechanisms in light of intestinal flora and intestinal immunity. Methods Thirty-six male Wistar rats were randomized equally into control group, UC model group, and E.faecium QH06 intervention group. The rats in the latter two groups were subjected to colonic enema with 5% TNBS/ethanol to induce UC, followed by treatment with intragastric administration of distilled water or E.faecium QH06 at the dose of 0.21 g/kg. After 14 days of treatment, the rats were examined for colon pathologies with HE staining. The mRNA and protein expression levels of IL-4, IL-10, IL-12, and IFN-γ in the colon tissues were detected using RT-qPCR and ELISA, and the expression of TLR2 protein was detected with immunohistochemistry and ELISA. Illumina Miseq platform was used for sequencing analysis of the intestinal flora of the rats with bioinformatics analysis. The correlations of the parameters of the intestinal flora with the expression levels of TLR2 and cytokines were analyzed. Results The rats with TNBS- induced UC showed obvious weight loss (P<0.01) and severe colon tissue injury with high pathological scores (P<0.01). The protein expression levels of IFN-γ, IL-12, and TLR2 (P<0.01) and the mRNA expression levels of IFN-γ, IL-12 and IL-10 (P<0.05) were significantly increased in the colon tissues of the rats with UC. Illumina Miseq sequence analysis showed that in UC rats, the Shannon index (P<0.05) ACE (P<0.01)and Chao (P<0.05) index for the diversity of intestinal flora both decreased with a significantly increased abundance of Enterobacteriaceae (P<0.01) and a lowered abundance of Burkholderiaceae (P<0.05). Compared with the UC rats, the rats treated with E.faecium QH06 showed obvious body weight gain (P< 0.05), lessened colon injuries, lowered pathological score of the colon tissue (P<0.05), decreased protein expressions of IFN-γ, IL-12, and TLR2 and mRNA expressions of IFN-γ and IL-12 (P<0.01 or 0.05), and increased protein expressions of IL-4 (P<0.05). The Shannon index ACE (P<0.05) and Chao (P<0.05) index of intestinal microflora were significantly increased, the abundance of Enterobacteriaceae was lowered and that of Burkholderiaceae and Rikenellaceae was increased in E.faecium QH06- treated rats (P< 0.01 or 0.05). Correlation analysis showed that IFN-γ was positively correlated with the abundance of Enterobacteriaceae, and IFN-γ was negatively correlated with the abundance of Prevotellaceae, Desulfovibrionaceae, norank_o_Mollicutes_RF39 and Clostridiales_vadinBB60_group; TLR2 was negatively correlated with Clostridiales_vadinBB60_group, norank_o_Mollicutes_RF39 and Prevotellaceae. Conclusion E.faecium QH06 can alleviate TNBS-induced colonic mucosal injury in rats, and its effect is mediated possibly by increasing the abundance of SCFA-producing bacteria such as Prevotellaceae and inhibiting abnormal immune responses mediated by TLR2. Related Articles | Metrics | Comments（0）

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VIPR1 promoter methylation promotes transcription factor AP-2α binding to inhibit VIPR1 expression and promote hepatocellular carcinoma cell growth in vitro NING Shiyu, HE Chunmei, GUO Zehao, ZHANG Hao, MO Zhijing Journal of Southern Medical University    2022, 42 (7): 957-965.   DOI: 10.12122/j.issn.1673-4254.2022.07.01 Abstract （1684）   HTML （85）    PDF（pc） （2191KB）（612）       Knowledge map    Save Objective To explore the transcriptional regulation mechanism and biological function of low expression of vasoactive intestinal peptide receptor 1 (VIPR1) in hepatocellular carcinoma (HCC). Methods We constructed plasmids carrying wild-type VIPR1 promoter or two mutant VIPR1 promoter sequences for transfection of the HCC cell lines Hep3B and Huh7, and examined the effect of AP-2α expression on VIPR1 promoter activity using dual-luciferase reporter assay. Pyrosequencing was performed to detect the changes in VIPR1 promoter methylation level in HCC cells treated with a DNA methyltransferase inhibitor (DAC). Chromatin immunoprecipitation was used to evaluate the binding ability of AP-2α to VIPR1 promoter. Western blotting was used to assess the effect of AP-2α knockdown on VIPR1 expression and examine the differential expression of VIPR1 in the two cell lines. The effects of VIPR1 overexpression and knockdown on the proliferation, cell cycle and apoptosis of HCC cells were analyzed using CCK8 assay and flow cytometry. We also observed the growth of HCC xenograft with lentivirus-mediated over-expression of VIPR1 in nude mice. Results Compared with the wild-type VIPR1 promoter group, co-transfection with the vector carrying two promoter mutations and the AP-2α-over-expressing plasmid obviously restored the luciferase activity in HCC cells (P<0.05). DAC treatment of the cells significantly decreased the methylation level of VIPR1 promoter and inhibited the binding of AP-2α to VIPR1 promoter (P<0.01). The HCC cells with AP-2α knockdown showed increased VIPR1 expression, which was lower in Huh7 cells than in Hep3B cells. VIPR1 overexpression in HCC cells caused significant cell cycle arrest in G2/M phase (P<0.01), promoted cell apoptosis (P<0.001), and inhibited cell proliferation (P<0.001), while VIPR1 knockdown produced the opposite effects. In the tumor-bearing nude mice, VIPR1 overexpression in the HCC cells significantly suppressed the increase of tumor volume (P<0.001) and weight (P<0.05). Conclusion VIPR1 promoter methylation in HCC promotes the binding of AP-2α and inhibits VIPR1 expression, while VIPR1 overexpression causes cell cycle arrest, promotes cell apoptosis, and inhibits cell proliferation and tumor growth. Related Articles | Metrics | Comments（0）

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Cheng's Juanbi Decoction enhances autophagy in rheumatoid arthritis fibroblast-like synoviocytes by suppressing the PI3K/Akt/mTOR signal axis SUN Guanghan, XU Xia, WAN Lei, NAN Shuling, WANG Yufeng, ZHAO Li, CHENG Hui, WANG Kun, LIU Ying, FANG Yanyan, SUN Lang, ZHU Jun Journal of Southern Medical University    2022, 42 (11): 1726-1731.   DOI: 10.12122/j.issn.1673-4254.2022.11.18 Abstract （1659）   HTML （20）    PDF（pc） （2851KB）（393）       Knowledge map    Save Objective To study the regulatory effect of Cheng's Juanbi Decoction (JBT) on autophagy in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) and role of PI3K/Akt/mTOR signaling axis in the mechanism mediating this effect. Methods CCK8 assay was used to determine the optimal concentration and treatment time of JBT for inhibiting the viability of RA- FLS. The effect of freeze-dried powder of JBT, RAPA, or both on morphology of the autophagosomes in RA-FLS was observed under transmission electron microscope, and the changes in the number of autophagosomes and autolysosomes were observed with autophagy double-labeled adenovirus experiment. RT-qPCR and Western blotting were used to detect the expression levels of the related indicators. Results The results of CCK8 assay showed that treatment with 0.5 mg/mL JBT for 12 h produced the optimal effect for inhibiting RA-FLS viability. Observation with transmission electron microscope and the results of the autophagy double-labeled adenovirus experiment both showed the presence of a small number of autophagosomes in control RA-FLS group, and treatment with JBT significantly increased the number of autophagosomes and lowered the number of autophagolysosomes in the cells. Compared with the control cells and the cells treated with JBT or RAPA alone, the cells treated with both JBT and RAPA showed significantly decreased mRNA levels of PI3K, Akt and mTOR (P<0.01) but without significant changes in their protein expressions (P>0.05); the combined treatment significantly inhibited the protein expressions of p-PI3K, p-Akt, p-mTOR, and P62 (P<0.05) and upregulated the protein expressions of Beclin-1 and LC3B (P<0.05) in the cells. Conclusion JBT can inhibit the survival rate of RA-FLS and increase the level of autophagy possibly through a mechanism that down-regulates PI3K/Akt/mTOR signaling pathway Related Articles | Metrics | Comments（0）

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Overexpression of miR-607 inhibits hepatocellular carcinoma cell growth and metastasis by down-regulating TRPC5 LI Chao, CHEN Shuangjiang, JIANG Yezhen Journal of Southern Medical University    2022, 42 (11): 1587-1593.   DOI: 10.12122/j.issn.1673-4254.2022.11.01 Abstract （1658）   HTML （946）    PDF（pc） （2165KB）（587）       Knowledge map    Save Objective To investigate the clinical implications of abnormal expression of miR-607 in hepatocellular carcinoma (HCC) and its influence on HCC cell proliferation and migration. Methods The expression of miR-607 in 45 pairs of HCC and adjacent tissues were detected with real- time PCR, and the correlation between miR-607 expression and clinicopathological features of the patients was analyzed. The effects of transfection with miR-607 mimics on proliferation, apoptosis, migration and invasion of two HCC cell lines (Huh-7 and HCCLM3) were evaluated using CCK-8 assay, flow cytometry, wound-healing assay and Transwell assay. A dual-luciferase reporter system was used to detect the direct binding between miR-607 and 3'-UTR of TRPC5 mRNA. Western blotting was used to measure the expressions of TRPC5, CCND1, MMP2 and phosphorylated Akt in the HCC cells. Results The expression of miR-607 was significantly decreased in HCC tissues (P=0.029) and HCC cell lines (P<0.05). In HCC patients, a low expression of miR-607 was associated with a larger tumor size (>5 cm, P=0.031), vascular invasion (P=0.027) and advanced TNM stages (III + IV, P=0.015). In the two HCC cell line, overexpression of miR-607 significantly inhibited cell proliferation, migration, and invasion and enhanced cell apoptosis (P<0.05). The results of dual-luciferase reporter assay confirmed that TRPC5 was a direct target of miR- 607 in HCC cells. Overexpression of miR-607 significantly inhibited the expressions of TRPC5, CCND1, and MMP2 and suppressed Akt phosphorylation in HCC cells (P<0.05). Conclusion A low expression of miR-607 in HCC is associated with poor clinicopathological phenotypes of HCC. Overexpression of miR-607 inhibits HCC growth and metastasis possibly by down- regulating TRPC5, which causes Akt signaling inactivation. Related Articles | Metrics | Comments（0）

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CD40LG is a novel immune- and stroma-related prognostic biomarker in the tumor microenvironment of invasive breast cancer GUO Li, MA Yinling, LI Ting, LI Jinping Journal of Southern Medical University    2022, 42 (9): 1267-1278.   DOI: 10.12122/j.issn.1673-4254.2022.09.01 Abstract （1610）   HTML （91）    PDF（pc） （5612KB）（547）       Knowledge map    Save Objective To identify tumor microenvironment (TME)- related genes associated with the occurrence of invasive breast cancer as potential prognostic biomarkers and therapeutic targets. Methods RNA transcriptome data and clinically relevant data were retrieved from TCGA database, and the StromalScore and ImmuneScore were calculated using the ESTIMATE algorithm. The differentially expressed genes (DEGs) were screened by taking the intersection. A protein-protein interaction network was established, and univariate COX regression analysis was used to identify the core genes among the DEGs. A core gene was selected for GSEA and CIBERSORT analysis to determine the function of the core gene and the proportion of tumor-infiltrating immune cells , respectively. Western blotting and qRT-PCR were performed to verify the expression level of CD40LG in breast cancer cell lines and clinical specimens. Results A total of 1222 samples (124 normal and 1098 tumor samples) were extracted from TCGA for analysis, from which 487 DEGs were identified. These genes were mainly enriched in immune-related pathways, and crossover analysis identified 11 key genes (CD40LG, ITK, CD5, CD3E, SPN, IL7R, CD48, CCL19, CD2, CD52, and CD2711) associated with breast cancer TME status. CD40LG was selected as the core gene, whose high expression was found to be associated with a longer overall survival of breast cancer patients (P=0.002), and its expression level differed significantly with TNM stage and tumor size (P<0.05). GSEA and CIBERSORT analyses indicated that CD40LG expression level was associated with immune activity in the TME. Western blotting and qRT-PCR showed that the protein and mRNA expression of CD40LG were significantly lower in breast cancer cells and cancer tissues than in normal breast cells and adjacent tissues. Conclusions The high expression of CD40LG in TME is positively correlated with the survival of patients with invasive breast cancer, suggesting its value as a potential new biomarker for predicting prognosis of the patients. Related Articles | Metrics | Comments（0）

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Value of ultrasonic S-Detect technique in diagnosis of breast masses CHENG Yangmei, XIA Qun, WANG Jun, XIE Hongjuan, YU Yi, LIU Haihua, YAO Zhizheng, HU Jinhua Journal of Southern Medical University    2022, 42 (7): 1044-1049.   DOI: 10.12122/j.issn.1673-4254.2022.07.12 Abstract （1592）   HTML （28）    PDF（pc） （1120KB）（359）       Knowledge map    Save Objective To evaluate the value of ultrasound S-Detect in the diagnosis of breast masses. Methods A total of 85 breast masses in 62 female patients were diagnosed by S-Detect technique and conventional ultrasound. The diagnostic efficacy of conventional ultrasound and S-Detect technique was analyzed and compared with postoperative pathological results as the gold standard. Results When operated by junior physicians, the diagnostic efficacy of conventional ultrasound was significantly lower than that of S-Detect technique (P<0.05), but this difference was not observed in moderatelyexperienced and senior physicians (P>0.05). S-Detect technique was positively correlated with the diagnostic results of seniorphysicians (r=0.97). Using S-Detect technique, the diagnostic efficacy did not differ significantly between the long axis sectionand its vertical section (P>0.05). Routine ultrasound showed a better diagnostic efficacy than S-Detect for breast masses with adiameter below 20 mm (P<0.05), but for larger breast masses, its diagnostic efficacy was significantly lower than that of S-Detect (P<0.05). Conclusion S-Detect can be used in differential diagnosis of benign and malignant breast masses, and its diagnostic efficiency can be comparable with that of BI-RADS classification for moderately experienced and senior physicians, but its diagnostic efficacy can be low for breast masses less than 20 mm in diameter. Related Articles | Metrics | Comments（0）

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FNDC1 is highly expressed in lung adenocarcinoma and closely related with poor prognosis HONG Haining, ZHU Haonan, LI Chao, ZANG Chao, SANG Haiwei, CHEN Liwei, WANG Ansheng Journal of Southern Medical University    2022, 42 (8): 1182-1190.   DOI: 10.12122/j.issn.1673-4254.2022.08.10 Abstract （1567）   HTML （56）    PDF（pc） （1853KB）（441）       Knowledge map    Save Objective To explore the expression of fibronectin type III domain containing 1 (FNDC1) protein in lung adenocarcinoma and its prognostic significance. Methods The expression of FNDC1 in lung adenocarcinoma was predicted by analysis of data from GEO database and GEPIA, and the results were verified by immunohistochemical staining in 92 pairs of clinical specimens of lung adenocarcinoma and adjacent tissues. We further analyzed the correlation of FNDC1 expression with the clinicopathological features of the patients, and evaluated its prognostic value using Cox survival analysis. Results Analysis of the data form GEO database and GEPIA showed a significantly higher expression level of FNDC1 in lung adenocarcinoma than in matched normal tissues (P<0.05). Kaplan-Meier survival analysis suggested that a high expression of FNDC1 protein was associated with a significantly shorter overall survival time of the patients (P<0.05). Immunohistochemistry of the clinical specimens also showed a significantly higher protein expression of FNDC1 in lung adenocarcinoma tissues than in paired adjacent tissues (P<0.001). A high expression of FNDC1 protein was significantly correlated with advanced clinical stage, T stage and N stage (P<0.05). Cox univariate and multivariate regression survival analysis indicated that an increased expression of FNDC1 was an independent risk factor for poor prognosis of the patients with lung adenocarcinoma (P<0.05). Conclusion FNDC1 protein is highly expressed in patients with lung adenocarcinoma and in closely related with the occurrence, progression and prognosis of the tumor, suggesting the value of FNDC1 protein as a potential biomarker for assessment of the survival and prognosis of patients with lung adenocarcinoma. Related Articles | Metrics | Comments（0）

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A discrimination model for differentiation of renal cell carcinoma from renal angiomyolipoma without visible fat: based on hierarchical fusion framework of multi-classifier MO Tianlan, WU Yuliang, YANG Ruimeng, ZHEN Xin Journal of Southern Medical University    2022, 42 (8): 1174-1181.   DOI: 10.12122/j.issn.1673-4254.2022.08.09 Abstract （1556）   HTML （43）    PDF（pc） （1215KB）（295）       Knowledge map    Save Objective To investigate the capabilities of classification models based on hierarchical fusion framework of multi-classifier using a random projection strategy for differentiation of renal cell carcinoma (RCC) from small renal angiomyolipoma (<4 cm) without visible fat (AMLwvf). Methods We retrospectively collected the clinical data from 163 patients with pathologically proven small renal mass, including 118 with RCC and 45 with AMLwvf. Target region of interest (ROI) delineation was performed on an unenhanced phase (UP) CT image slice displaying the largest lesion area. The radiomics features were used to establish a hierarchical fusion method. On the projection-based level, the homogeneous classifiers were fused, and the fusion results were further fused at the classifier-based level to construct a multi-classifier fusion system based on random projection for differentiation of AMLwvf and RCC. The discriminative capability of this model was quantitatively evaluated using 5-fold cross validation and 4 evaluation indexes [specificity, sensitivity, accuracy and area under ROC curve (AUC)]. We quantitatively compared this multi-classifier fusion framework against different classification models using a single classifier and several multi-classifier ensemble models. Results When the projection number was set at 10, the proposed hierarchical fusion differentiation framework achieved the best results on all the evaluation measurements. At the optimal projection number of 10, the specificity, sensitivity, average accuracy and AUC of the multi-classifier ensemble classification system for differentiation between AMLwvf and RCC were 0.853, 0.693, 0.809 and 0.870, respectively. Conclusion The proposed model constructed based on a multi-classifier fusion system using random projection shows better performance to differentiate RCC from AMLwvf than the AMLwvf and RCC discrimination models based on a single classification algorithm and the currently available benchmark ensemble methods. Related Articles | Metrics | Comments（0）

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Cuprous oxide nanoparticles-based photothermal and chemodynamic synergistic therapy inhibits proliferation and migration of gastric cancer cells in vitro WEN Haifei, HUANG Xianying Journal of Southern Medical University    2022, 42 (11): 1732-1738.   DOI: 10.12122/j.issn.1673-4254.2022.11.19 Abstract （1555）   HTML （28）    PDF（pc） （2878KB）（362）       Knowledge map    Save Objective To investigate the physicochemical characterization of cuprous oxide (Cu2O) nanoparticles and assess its antitumor effect against gastric cancer cells in vitro. Methods The morphology, particle size and Fenton-like properties of Cu2O nanoparticles were analyzed using transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential analysis and ultraviolet absorption spectroscopy. CCK-8 assay and Transwell experiments were used for evaluating the in vitro anti-tumor effect of the nanometers in gastric cancer cells. Results The prepared Cu2O nanoparticles had a quasi-circular structure with a diameter of about 100 nm. The temperature of the nanoparticles increased from 25 to 50 ℃ after irradiation with near-infrared light (NIR, 0.5W/cm2) for 5 min. At a nearly neutral pH (pH=6.5), the nanoparticles catalyzed the generation of a large amount of reactive oxygen species (ROS). CCK-8 assay and Transwell experiment showed that Cu2O nanoparticles concentration-dependently inhibited the proliferation, invasion and migration of gastric cancer cells. Conclusion Cu2O nanoparticles have good photothermal and chemokinetic properties with a strong anti-tumor effect, and can potentially serve as a new therapeutic agent for gastric cancer treatment. Related Articles | Metrics | Comments（0）

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Fkbp38 deletion induces premature ovarian insufficiency in mice by activating mTOR signaling and inducing granulosa cell apoptosis ZHOU Yuxia, ZHAO Huihui, SHUAI Ling, SHE Jiajie, DIAO Ruiying, WANG Liping Journal of Southern Medical University    2022, 42 (11): 1611-1617.   DOI: 10.12122/j.issn.1673-4254.2022.11.04 Abstract （1550）   HTML （52）    PDF（pc） （2409KB）（440）       Knowledge map    Save Objective To investigate the role of tacrolimus-binding protein 38 (FKBP38) in follicle development and the mechanism by which Fkbp38 gene deletion causes premature ovarian insufficiency (POI). Methods The Cre-loxp system was used to construct oocyte-specific Fkbp38 knockout transgenic mice. The genotype of the transgenic mice was identified using PCR, and the expression of FKBP38 in the oocytes was verified. The numbers of primordial follicles, primary follicles, secondary follicles and antral follicles in Fkbp38 knockout mice and non-transgenic littermate control mice were counted with HE staining under a microscope for analyzing the effect of Fkbp38 deletion on follicular development. The fertility and serum sex hormone levels of the mice were determined by reproduction experiments and ELISA to assess ovarian function. Ovarian granulosa cell apoptosis of the mice was assessed using TUNEL assay. The activity of the downstream target protein of phosphorylated ribosomal S6 (PS6) of mTOR signaling pathway was detected, and the expressions of BCL-2 and BAX proteins were determined using immunofluorescence assay for assessing oocyte development in the mice. Results The oocyte-specific Fkbp38 knockout transgenic mouse model was successfully constructed, which showed decreased fertility, disordered sex hormone levels, and significantly reduced primordial follicles, primary follicles and secondary follicles in the ovary (P<0.05), demonstrating POI-like changes. Compared with the control mice, oocyte- specific Fkbp38 knockout caused activation of the mTOR signaling pathway, significantly increased apoptosis of the granulosa cells, and obviously increased the BAX/BCL-2 ratio by increasing BAX expression and reducing BCL-2 expression in the oocytes (P<0.05). Conclusion FKBP38 plays an important role in follicle development, and Fkbp38 gene deletion in mice causes POI possibly by activating the mTOR signaling pathway and inducing granulosa cell apoptosis. Related Articles | Metrics | Comments（0）

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JAG1 promotes migration, invasion, and adhesion of triple-negative breast cancer cells by promoting angiogenesis LIU Junping, SHI Yutong, WU Minmin, XU Mengqi, ZHANG Fengmei, HE Zhiqiang, TANG Min Journal of Southern Medical University    2022, 42 (7): 1100-1108.   DOI: 10.12122/j.issn.1673-4254.2022.07.21 Abstract （1536）   HTML （40）    PDF（pc） （3913KB）（589）       Knowledge map    Save Objective To investigate the effect of JAG1 on the malignant phenotype of triple-negative breast cancer (TNBC) and its role in angiogenesis in breast cancer microenvironment. Methods The expressions of Notch molecules were detected in human TNBC 231 and 231B cells using RT-qPCR. Five female nude mice were inoculated with 231 cells and another 5 with 231B cells into the mammary fat pads, and 4-6 weeks later, the tumors were collected for immunohistochemical and immunofluorescence tests. 231 cells and 231B cells were treated with recombinant JAG (rJAG) protein and DAPT, respectively, and changes in their malignant phenotypes were assessed using CCK-8 assay, Hoechst 33258 staining, wound healing assay, Transwell chamber assay and endothelial cell adhesion assay. Western blotting was used to detect the changes in the expressions of proteins related with the malignant phenotypes of 231 and 231B cells. The effects of conditioned medium (CM) derived from untreated 231 and 231 B cells, rJAG1-treated 231 cells and DAPT-treated 231B cells on proliferation and tube formation ability of cultured human umbilical vein endothelial cells (HUVECs) were evaluated using CCK-8 assay and tube-forming assay. Results The expression of JAG1 was higher in 231B cells than in 231 cells (P<0.05). Tumor 231B showed higher expression of VEGFA and CD31. Compared with 231-Blank group, the migration, invasion and adhesion of 231 cells in 231-rJAG1 were significantly enhanced (P<0.05). Protein levels of Twist1 and Snail increased (P<0.01), anti-apoptotic protein Bcl-2 increased (P<0.05), while DAPT inhibited the related phenomena and indicators of 231B. The 231-rJAG1-CM increased the cell number and tubule number of HUVEC (P<0.05). Conclusion JAG1 may affect the malignant phenotype of TNBC and promote angiogenesis in the tumor microenvironment. Related Articles | Metrics | Comments（0）

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Astragalus polysaccharide protects against blood-brain barrier damage in MCAO rats by inhibiting P2X7R channel YUAN Qiao, XIE Liying, CHEN Chaojun Journal of Southern Medical University    2022, 42 (11): 1705-1711.   DOI: 10.12122/j.issn.1673-4254.2022.11.15 Abstract （1530）   HTML （24）    PDF（pc） （1361KB）（440）       Knowledge map    Save Objective To investigate the protective effect of astragalus polysaccharide (APS) against blood-brain barrier in a rat model of middle cerebral artery occlusion (MCAO) and the role of P2X7R channel in the protective mechanism. Methods In rat microglial cell models of oxygen and glucose deprivation (OGD) or ATP treatment, the formation of blood-brain barrier in vitro was assessed using the leak test, and the effect of APS on the permeability of the blood-brain barrier was determined using LC-MS. In 12 SD rats, MCAO model was established followed by treatment with intraperitoneal injection of normal saline (n=6) or APS (45 mg/kg, n=6) for 3 consecutive days, with another 6 rats without MCAO receiving saline injections as the control group. The permeability of the blood-brain barrier of the rats was evaluated by determining Evans blue (EB) extravasation, and ATP content in the brain tissue was detected using ELISA; the expression levels of matrix metalloproteinase-9 (MMP-9) and P2X7R in the brain tissue were detected with Western blot. Results In the in vitro cell model of OGD or ATP treatment, APS treatment obviously promoted the repair of blood-brain barrier integrity. In the rat models, the EB content in the brain tissue and the blood-brain barrier permeability increased significantly in MCAO+saline group and MCAO+APS group as compared with those in the control group (P<0.01). Compared with saline treatment, APS treatment significantly decreased EB content in the brain tissue and improved the blood-brain barrier permeability in the MCAO rats (P<0.05). MCAO caused a significant reduction of ATP content and obviously increased the expression levels of MMP-9 and P2X7R in the brain tissue of the rats (P<0.01), and these changes were significantly alleviated after APS treatment (P<0.01 or 0.05). Conclusion APS can protect the brain tissue of MCAO rats by stabilizing the internal environment, down-regulating the expression of MMP-9 and improving the permeability of blood-brain barrier under cerebral ischemia and hypoxia, and its mechanism may involve the inhibition of P2X7R channel. Related Articles | Metrics | Comments（0）

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FUT8 modulates galectin-3 expression to regulate TGF-β1-mediated fibrosis of lung fibroblasts GAO Weiwei, LIU Daijian, ZHANG Xiaoping, FENG Qingqing, LIU Ying Journal of Southern Medical University    2022, 42 (8): 1166-1173.   DOI: 10.12122/j.issn.1673-4254.2022.08.08 Abstract （1509）   HTML （34）    PDF（pc） （1449KB）（483）       Knowledge map    Save Objective To investigate the regulatory role of α-1,6-fucosyltransferase (FUT8) in TGF-β1-induced proliferation, migration and fibrosis of human embryonic lung fibroblasts (MRC-5 cells) and explore the underlying molecular mechanism. Methods C57/BL6 mice were randomized into 4 groups for treatment with saline (control group), bleomycin, bleomycin+sh-NC or bleomycin + sh-FUT8, and pulmonary fibrosis was observed using Masson staining. MRC-5 cells were transfected with si-NC, FUT8 siRNA (si-FUT8), or both si-FUT8 and a galectin-3 (Gal-3) overexpression plasmid (pcDNA3.1-Gal) prior to TGF-β1 treatment, and the changes in cell proliferation and migration were assessed using CCK-8 assay, BrdU assay, and wound healing assay; the changes in the expression levels of α-SMA, collagen I (COLIA1) and extracellular matrix fibronectin (FN) were detected with real-time quantitative PCR (RT-qPCR) and Western blotting. The interaction of FUT8 and Gal-3 was tested using coimmunoprecipitation (Co-IP) assay, and the effect of FUT8 silencing on Gal-3 and FAK/Akt signaling pathways was analyzed. Results FUT8 knockdown significantly reduced bleomycin-induced extracellular collagen deposition in the lung tissues of the mice. Silencing FUT8 obviously inhibited cell proliferation (P<0.05) and migration mediated by TGF-β1. FUT8 knockdown down-regulated the mRNA and protein levels of α-SMA, COLIA1 and FN (P<0.05) in the cells. Coimmunoprecipitation analysis showed that FUT8 interacted with Gal-3. Silencing FUT8 significantly down-regulated Gal-3 expression and inhibited the activation of the FAK/Akt signaling pathway (P<0.05). Overexpression of Gal-3 obviously reversed the effects of FUT8 silencing on cell proliferation, migration and fibrosis (P<0.05). Conclusion FUT8 regulates TGF-β1-induced proliferation, migration and fibrosis of MRC-5 cells by modulating Gal-3 expression, in which the FAK/Akt pathway may play a role. Related Articles | Metrics | Comments（0）

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Biomechanical analysis of miniplate fixation systems in restorative laminoplasty for spinal canal reconstruction CHEN Jianmin, LIU Guoyin, BAO Tianyi, BAI Tianting, ZHANG Erlai, ZHAO Jianning Journal of Southern Medical University    2023, 43 (3): 331-339.   DOI: 10.12122/j.issn.1673-4254.2023.03.01 Abstract （1485）   HTML （56）    PDF（pc） （1122KB）（314）       Knowledge map    Save Objective To investigate the biomechanical properties of H-shaped and L-shaped miniplate fixation systems (H-MFS and L-MFS, respectively) in restorative laminoplasty for spinal canal reconstruction (RL-SCR). Methods Laminectomy was performed in a 3D printed L4 vertebral model followed by RL-SCR using H-MFS or L-MFS, and the biomechanical properties of the reconstructed models were evaluated using static and dynamic compression tests. Biomechanical analyses of RL-SCR were also conducted in finite element models of the L3-L5 vertebrae with normal assignment (NA), laminectomy, or fixation with H-MFS or L-MFS, and the range of motion (ROM) of L3-L4 and L4-L5 was evaluated. Results In static compression test, the sustained yield load, compression stiffness, yield displacement and axial displacement- axial load were all significantly greater in H-MFS group (P<0.05). Door closing, lamina collapse and plate breakage occurred in all the models in L-MFS group, and only some models in H-MFS group showed plate cracks and screw loosening. In dynamic compression tests, the peak load in H-MFS group reached 873 N (which was 95% of the average yield load in static compression), significantly greater than that in L-MFS group (P<0.05). The ultimate load in L-MFS group was only 46.59% of that in H-MFS group (P>0.05). In finite element analysis, the ROM of the L3-L4 and L4- L5 segments were significantly smaller in NA, H-MFS and L-MFS groups than in laminectomy group. Compared with NA group, H-MFS group showed a greater ROM during extension, and L-MFS group showed greater ROM in flexion, extension, bending, and rotation; The overall ROM of the vertebral segments decreased in the order of laminectomy group, L-MFS group, H-MFS group, and NA group. Conclusion Laminectomy causes structural destruction of the posterior column of the spine to affect its biomechanical stability. RL-SCR can effectively maintain the biomechanical stability of the spine, and H-MFS is superior to L-MFS in maintaining the integrity and biomechanical properties of the reconstructed spinal canal. Related Articles | Metrics | Comments（0）

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MiR-372-5p regulates PI3K/AKT/CXCL12 signaling pathway by targeting PTEN to promote colorectal cancer cell metastasis SHI Xiuru, WEI Ke, WU Yulun, WANG Wenrui, YANG Qingling, CHEN Changjie Journal of Southern Medical University    2022, 42 (8): 1191-1197.   DOI: 10.12122/j.issn.1673-4254.2022.08.11 Abstract （1482）   HTML （47）    PDF（pc） （2723KB）（396）       Knowledge map    Save Objective To investigate whether miR-372-5p regulates PI3K/AKT/CXCL12 signaling pathway by targeting PTEN to promote metastasis of colorectal cancer cells. Methods We detected the differential expression of miR-372-5p using RT-qRCR in colorectal cancer and adjacent tissues, colorectal cancer cells and normal intestinal epithelial cells. Bioinformatic analysis and double luciferase assay were performed for verification of the targeting relationship between miR-372-5p and PTEN. Western blotting was used to assess the effects of transfection with miR-372-5p inhibitor and miR-372-5p mimics alone, co-transfection with miR-372-5p inhibitor and si-PTEN, and co-transfection with miR-372-5p mimics and PI3K inhibitor on the expressions of PTEN and CXCL12 and the activation of PI3K/AKT signal pathway; Transwell assay and scratch assay were used to examine the changes in the migration ability of the transfected cells, the cells co-transfected with miR-372-5p mimics and si-CXCL12, and the cells treated with conditioned medium from HCT116 cells transfected with miR-372-5p mimics. Results The expression of miR-372-5p was significantly higher in colorectal cancer tissues than in adjacent tissues, and higher in HCT116 and SW620 cells than in NCM460 cells (P<0.01). Double luciferase assay confirmed that PTEN was a potential target gene of miR-372-5p (P<0.05). Transfection of HCT116 cells with miR-372-5p mimics obviously decreased PTEN protein expression, increase CXCL12 expression and the phosphorylation level of AKT, and lowered the cell migration ability, while transfection with miR-372-5p inhibitor produced the opposite effects (P<0.05); si-PTEN obviously neutralized the effect of miR-372-5p inhibitor (P<0.01). PI3K inhibitor significantly decreased CXCL12 expression and inhibited the cell migration (P<0.05), and this effect was mitigated by miR-372-5p mimics (P<0.01). Treatment with the conditioned medium from HCT116 cells transfected with miR-372-5p mimics significantly enhanced the migration ability of NCM460 cells, and this effect was suppressed by transfection with si-CXCL12 (P<0.01). Conclusion MiR-372-5p activates PI3K/AKT signaling pathway by targeting PTEN and up-regulates CXCL12 expression to promoting metastasis of colorectal cancer cells. Related Articles | Metrics | Comments（0）

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Diethylhexyl phthalate induces anxiety-like behavior and learning and memory impairment in mice probably by damaging blood-brain barrier LI Fan, ZHU Yanyan, SUN Xiaoming, HU Huijuan, ZHOU Miaomaio, BAI Yixue, HU Hao Journal of Southern Medical University    2022, 42 (8): 1237-1243.   DOI: 10.12122/j.issn.1673-4254.2022.08.17 Abstract （1480）   HTML （40）    PDF（pc） （1754KB）（295）       Knowledge map    Save Objective To investigate the effects of diethylhexyl phthalate (DEHP) exposure on anxiety-like behaviors and learning and memory ability in mice and explore the underlying mechanism. Methods Forty male ICR mice were randomized equally into control group (0 mg/kg) and 10, 50 and 100 mg/kg DEHP exposure groups, in which the mice were exposed to DEHP at the indicated doses by gavage for 4 weeks. After the treatments, the mice were assessed for behavioral changes using open filed test, elevated plus-maze and Morris water maze test. Brain tissues were collected from the mice for determination of malondialdehyde (MDA) content, pathologies and expressions of ZO-1 and occludin in the hippocampus. Results Compared with the control group, the mice with DEHP exposure for 4 weeks exhibited no significant body weight change (P>0.05) but presented with obvious behavioral changes, manifested by reduced movement distance (P<0.05) and time spent in the center of the open field (P<0.05), reduced movement distance (P<0.05) and time spent in the open arm of the elevated maze (P<0.05), significantly increased latency of searching for the platform (P<0.05), and decreased frequency of crossing the platform (P< 0.05). HE staining showed obvious vertebral cell death in the hippocampal CA1 to CA3 regions of the mice with DEHP exposure. The exposed mice showed significantly increased MDA content and decreased expressions of ZO-1 and occludin at both the mRNA and protein levels in the hippocampus (P<0.05 or 0.01). Multivariate linear regression analysis suggested a close correlation between anxiety-like behaviors and learning and memory abilities in DEHP-exposed mice. Conclusion DEHP exposure may cause damages of the blood-brain barrier and the pyramidal cells in the hippocampus of mice, thereby inducing anxiety-like behaviors and learning and memory impairment. Related Articles | Metrics | Comments（0）