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    Basic research
    Effect of BRCA1 R1325K mutation on proliferation and apoptosis of gallbladder cancer cells
    YANG Jingxiao, JIA Ziyao, WU Wenguang, WU Xiangsong, ZHANG Fei, LI Huaifeng, ZHU Yidi, LI Maolan
    2023, 43 (9):  1071-1079. 
    doi: 10.3969/j.issn.1674-8115.2023.09.001

    Abstract ( 110 )   HTML ( 7 )   PDF (3822KB) ( 77 )  

    Objective ·To investigate the effects of breast cancer susceptibility gene 1 (BRCA1) R1325K mutation [arginine (R) to lysine (K) mutation at amino acid 1325] on the proliferation and apoptosis of gallbladder cancer cell lines GBC-SD and NOZ. Methods ·BRCA1 wild-type overexpression lentivirus, BRCA1 R1325K mutation overexpression lentivirus, and negative control lentivirus were used to construct the stable transgenic strains of gallbladder carcinoma, cell lines GBC-SD and NOZ. The cells were divided into the control group without the target gene, the BRCA1 wild-type group, and the BRCA1 R1325K mutation group. The expression of target protein was verified by Western blotting. The BRCA1 R1325K mutant gallbladder cancer cells were treated with 20 μmol/L Olaparib, a BRCA1 mutation inhibitor. Gallbladder cancer cell lines were divided into the control group, the BRCA1 wild-type group, the BRCA1 R1325K mutation group, and the BRCA1 R1325K mutation+Olaparib group according to the target gene expression and whether or not the inhibitor was added. The effect of BRCA1 R1325K mutation on proliferation and clonogenesis ability of gallbladder cancer cell lines GBC-SD and NOZ was observed by CCK8 assay and clonogenesis assay, respectively. The effect of BRCA1 R1325K mutation on apoptosis of gallbladder cancer cell lines GBC-SD and NOZ was observed by TUNEL assay. The expressions of apoptosis-related proteins, cleaved PARP, Bcl-2 and Bax, were detected by Western blotting. The inhibitor Olaparib was used to treat the BRCA1 R1325K mutant gallbladder cancer cell lines GBC-SD and NOZ. The phenotypic changes (promoting proliferation, enhancing clonogenesis and inhibiting apoptosis) induced by BRCA1 R1325K mutation were tested in the presence of Olaparib to determine whether the changes could be reversed by the inhibitor. Results ·The results of CCK8 assay and clonogenesis assay showed that BRCA1 R1325K mutation could promote the proliferation of gallbladder cancer cell lines GBC-SD and NOZ, and improve their clonal formation ability, compared with the control group and the BRCA1 wild-type group. Olaparib inhibited the proliferation of gallbladder cancer cell lines overexpressing BRCA1 R1325K mutation (P<0.05). Through TUNEL and Western blotting, it was found that overexpression of wild-type BRCA1 could induce the apoptosis of gallbladder cancer cell lines GBC-SD and NOZ, compared with the control group. Compared with the control group and the BRCA1 wild-type group, the BRCA1 R1325K mutation group had anti-apoptotic effect, in which the expression of apoptosis-inhibiting protein Bcl-2 increased and the expression of pro-apoptotic protein Bax decreased (P<0.05). Conclusion ·BRCA1 R1325K mutation can promote the proliferation of GBC-SD and NOZ cell lines and inhibit their apoptosis.

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    Effect of Piezo1 on osteogenic differentiation of mouse bone marrow mesenchymal stem cells C3H10T1/2 based on CRISPR/Cas9
    GAO Xin, YANG Yiling, HUANG Xiangru, DAI Qinggang, JIANG Lingyong
    2023, 43 (9):  1080-1088. 
    doi: 10.3969/j.issn.1674-8115.2023.09.002

    Abstract ( 165 )   HTML ( 14 )   PDF (3275KB) ( 108 )  

    Objective ·To investigate the effect of Piezo1 on osteogenic differentiation of mouse mesenchymal stem cells C3H10T1/2 cell line based on CRISPR/Cas9 system that can achieve stable gene knockout. Methods ·According to the principle of CRISPR/Cas9 target design principle, two single guide RNAs (sgRNAs) were designed to construct lentivirus expressing Cas9 and lentivirus expressing sgRNA by using Lenti-Cas9-GFP and Lenti-U6-sgRNA-mCherry vectors. After the C3H101/2 cells were transfected with two types of lentiviruses, flow cytometry was used to screen mCherry- and GFP-positive cells. The monoclonal cells were selected, and amplified by PCR and agarose gel electrophoresis, and finally the monoclonal cell line with Piezo1 gene fragment knocked out was obtained. Sequencing, quantitative realtime PCR (qPCR) and immunofluorescence were performed to verify the the knockout efficiency of the constructed Piezol knockout C3H10T1/2 cells (CPK). CCK-8 assay was used to detect the effect of knocking out Piezo1 on cell proliferation; in vitro osteogenic induction differentiation was performed on successfully constructed Piezo1 gene knockout cells, and alkaline phosphatase (ALP) staining and alizarin red staining were used to investigate the effect of Piezo1 on osteogenic ability. Results ·Positive clone was obtained in bacterial fluid of monoclonal cell lines with Piezol knocked out after PCR amplification and agarose gel electrophoresis. Sequencing analysis showed that a stop condon TGA was produced in exon 4 of Piezo1 gene in advance, so that the protein could not be translated correctly. qPCR verified that Piezo1 gene in CPK was inhibited at mRNA level; Immunofluorescence showed that the knockout efficiency of Piezo1 gene in CPK was high, which basically hindered the expression of Piezo1 in cells. CCK-8 assay showed that the cell proliferation ability decreased after knocking out Piezo1 (P<0.05); The results of ALP staining and alizarin red staining showed that the osteogenic ability of cells decreased after knocking out Piezo1(P<0.05). The mRNA expression levels of osteogenetic-related genes such as α 1 type Ⅰ collagen (Col1a1),Runt-related transcription factor 2 (Runx-2),osterix (Osx) and alkaline phosphatase (Alp)in CPK decreased significantly (all P<0.05). Conclusion ·Piezo1 knockout C3H10T1/2 cells based on CRISPR/Cas9 system is constructed successfully and the osteogenic activity of stable Piezo1 knockout cell line is hindered significantly.

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    Renal protective effect and mechanism research of hypoxia inducible factor-1α inhibitor YC-1 in diabetic nephropathy mice
    JIA Junjie, XING Haifan, ZHANG Qunzi, LIU Qiye, WANG Niansong, FAN Ying
    2023, 43 (9):  1089-1098. 
    doi: 10.3969/j.issn.1674-8115.2023.09.003

    Abstract ( 118 )   HTML ( 13 )   PDF (6166KB) ( 117 )  

    Objective ·To investigate the effect of hypoxia inducible factor-1α (HIF-1α) inhibitor YC-1 on the progression of diabetic nephropathy (DN) in mice and the potential mechanism. Methods ·Ten-week-old male db/db mice (DN model) and their nondiabetic wild-type (WT) littermates were divided into 4 groups (n=6) according to whether treated with YC-1 or not: WT group, WT+YC-1 group, DB group, and DB+YC-1 group. The treatment groups were intraperitoneally injected with YC-1 (20 mg·kg-1) once a day, while the non-treatment groups received the same volumes of DMSO injection. After a total of 8 weeks of intervention, blood glucose, body weight, and kidney weight of all mice were measured. Serum, urine and kidney tissue samples were harvested. Serum creatinine, urinary albumin-to-creatinine ratio (UACR), and urine neutropil gelatinase-associated lipocalin (NGAL) levels were detected. The kidneys were stained with ?hemat?oxyli?n-eosin (H-E) and periodic acid-Schiff (PAS) to observe the pathological changes. Masson staining was used to detect fibrosis, collagen-Ⅰ was detected by immunohistochemistry, and α-smooth muscle actin (α-SMA) was detected by Western blotting. The expression of HIF-1α was detected by both Western blotting and immunohistochemistry. TUNEL staining and Western blotting for apoptosis-related proteins were used to observe the cell apoptosis level. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) level were detected by the kits. Endoplasmic reticulum stress (ERS) markers, including immunoglobulin heavy chain binding protein (BiP, also known as GRP78), phospho-protein kinase R-like endoplasmic reticulum kinase (p-PERK), total PERK, phospho-eukaryotic initiation factor 2α (p-eIF2α), total eIF2α, activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP), were determined by Western blotting. Results ·Compared with the WT group, the DB group showed significant rise of blood glucose, loss of renal function, severe kidney histopathology injuries and kidney fibrosis, increase of renal HIF-1α expression, and aggravated oxidative stress and ERS. Whilst there were no significant changes in blood glucose, YC-1 treatment notably reduced kidney weight/body weight ratio, serum creatinine, UACR, and urine NGAL levels in db/db mice. YC-1 treatment ameliorated kidney histopathology injuries and kidney fibrosis, and decreased the expressions of collagen-Ⅰ and α-SMA. YC-1 treatment also reduced the number of TUNEL positive cells, the expression of HIF-1α and pro-apoptotic proteins including BAX and cleaved caspase-3, and MDA level in the kidneys of db/db mice, while promoting anti-apoptotic protein BCL-2 expression and SOD activity. The expressions of ERS markers GRP78, p-PERK, p-eIF2α, ATF4, and CHOP were likewise significantly decreased in DB+YC-1 group. Conclusion ·HIF-1α inhibitor YC-1 inhibits oxidative stress and abnormal activation of ERS, improving cell apoptosis and fibrosis in the kidneys of DN mice, which would attenuate the aggravation of pathological damage and loss of kidney function.

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    Structural analysis of full-length lysine acetyltransferase 7 by cryo-electron microscopy
    ZHENG Guopei, CAO Qin, SHEN Jianfeng
    2023, 43 (9):  1099-1106. 
    doi: 10.3969/j.issn.1674-8115.2023.09.004

    Abstract ( 89 )   HTML ( 4 )   PDF (3636KB) ( 62 )  

    Objective ·To analyze the full-length protein structure of human-derived lysine acetyltransferase 7 (KAT7) using cryo-electron microscopy (Cryo-EM) and to obtain the profile information of human-derived KAT7. Methods ·The recombinant protein expression plasmid pGEX-4T1-GST-KAT7 was constructed by using the pGEX-4T1 vector and the full-length gene of human-derived KAT7, and the KAT7 protein was expressed in the prokaryotic protein expression system BL21 (DE3). The GST-KAT7 recombinant protein was obtained by using GST affinity chromatography. After removing the GST protein tag with TEV protease, KAT7 was further isolated and purified by HiLoad 16/600 Superdex 75 pg volume exclusion chromatography. The obtained protein samples were identified by Western blotting, and the samples were screened. The protein morphology was observed under negative-stain electron microscopy, and data were collected by using Cryo-EM. The protein particles were selected and the spatial structure of the full-length KAT7 was analyzed with the Cryo-EM analysis software CryoSparc. The MYST structural domain model (5GK9) in the Protein Data Bank (PDB) and AlphaFold prediction model of KAT7 were matched with the generated structural model by UCSF Chimera software. Results ·The full-length protein of human-derived KAT7 was successfully purified by affinity chromatography, and high purity KAT7 was obtained by volume exclusion chromatography. After identifying KAT7 by Western blotting, the spatial structure of KAT7 full-length protein was initially resolved by Cryo-EM and single-particle reconstruction techniques, and a preliminary three-dimensional structure model with a resolution of about 10 ? was obtained by three-dimensional optimization. The spatial structure of KAT7 full-length protein was irregular and semi-loop-shaped, and the existing MYST domain model (PDB: 5GK9) can be matched into the C-terminal part of the KAT7 full-length model. The adjusted AlphaFold prediction model can also match the KAT7 full-length structure model. Conclusion ·A preliminary analysis of the spatial structure model of full-length protein of human-derived KAT7 is performed by using Cryo-EM.

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    Study on the significance and mechanism of ASGR1 in hepatocellular carcinoma
    LI Qianyu, GUO Wenyun, QIAN Yifei, LI Songling, ZHU Zijun, LIU Yanfeng
    2023, 43 (9):  1107-1114. 
    doi: 10.3969/j.issn.1674-8115.2023.09.005

    Abstract ( 149 )   HTML ( 14 )   PDF (6113KB) ( 113 )  

    Objective ·To explore the significance and mechanism of asialoglycoprotein receptor 1 (ASGR1) in hepatocellular carcinoma. Methods ·The expression of ASGR1 in patients with liver cancer in The Cancer Genome Atlas (TCGA) database was analyzed by R language and the related survival curves were drawn. The Human Protein Atlas (HPA) database was used to obtain the immunohistochemistry (IHC) data of normal human liver tissue and liver cancer tissue to analyze the protein expression of ASGR1. By using the hydrodynamic tail vein injection (HTVI) delivery method, Asgr1 was knocked out in the liver of fully immune mice to explore its tumorigenic function invivo. Gene knockout efficiency was verified by Western blotting (WB). The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and correlation analysis were performed by using R language. The GSEA hallmark correlation pathway analysis was performed by using Gene Set Enrichment Analysis (GSEA) software. The expression level of key genes of glycolysis in mouse liver cancer tissue was verified by quantitative real-time PCR (qPCR). Results ·ASGR1 was significantly low-expressed in liver cancer tissue, and the low expression of ASGR1 in liver cancer patients was associated with poorer overall survival (OS), disease-free interval (DFI), progression-free interval (PFI), and disease-specific survival (DSS). The higher the degree of tumor grade, the lower the expression level of ASGR1 in patients with liver cancer. Immunohistochemistry showed that the protein expression of ASGR1 in normal human liver tissue was significantly higher than that in liver cancer tissue. In an immunocompetent mouse model of hepatocellular carcinoma, knockout of endogenous Asgr1 in mice increased the size and number of tumor nodules in liver tissue. In the TCGA database, patients with liver cancer in the ASGR1 low-expression group were enriched in multiple cancer and metabolic pathways. The expression of ASGR1 was negatively correlated with some key genes of glycolysis. The level of glycolysis in liver cancer tissues of mice in the Asgr1 knockout group was higher than that in the control group. It was suggested that the low expression of ASGR1 be likely to promote the growth and development of liver cancer and strengthen metabolic reprogramming to promote the anabolic development of tumors. Conclusion ·The expression of ASGR1 is significantly reduced in patients with liver cancer, which is positively correlated with the prognosis of patients. Knocking out Asgr1 in mice can promote the occurrence and development of hepatocellular carcinoma. ASGR1 can be used as a potential biomarker for poor prognosis of liver cancer and a new target for potential treatment.

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    Sevoflurane inhibits the differentiation and development of neural progenitor cells into neurons in the prefrontal cortex of newborn mice
    LIU Siyu, ZHANG Lei
    2023, 43 (9):  1115-1130. 
    doi: 10.3969/j.issn.1674-8115.2023.09.006

    Abstract ( 89 )   HTML ( 9 )   PDF (6319KB) ( 116 )  

    Objective ·To investigate the mechanism of sevoflurane damaging neuron development in the prefrontal cortex (PFC) of the neonatal mice after single or multiple sevoflurane anesthesia based on the single-cell RNA sequencing (scRNA-seq). Methods ·The neonatal mice were divided into multiple anesthesia exposure (Sev3) group, single anesthesia exposure (Sev1) group, and control group with 3 mice each. The Sev3 group received anesthesia with 3% sevoflurane and 60% O2 on postnatal day 6, 7, and 8, and the Sev1 group received anesthesia only on postnatal day 6. The PFC from mice in the 3 groups was harvested on postnatal day 9 for scRNA-seq. PFC cell profiles and neuronal subpopulation profiles of newborn mice after sevoflurane anesthesia were obtained by UMAP (uniform manifold approximation and projection) clustering, RNA velocity analysis, and transcription factor analysis (SCENIC). Differential expression gene analysis was performed. The biological processes and pathways of the differential genes were investigated through Gene Ontology (GO) database and Kyoto Encyclopedia of Genes and Genomes (KEGG) database; QuSAGE analysis was used to describe the activation of the cell cycle and Hippo signaling pathway gene sets. Transcript enrichment and stemness of PFC neuronal lineage cells of neonatal mice after sevoflurane anesthesia was determined by CytoTRACE score. The differentiation trajectory of PFC neurons was determined by using pseudo-time analysis, and the developmental nodes were resolved by BEAM analysis to identify key genes that determine different cell fates. Results ·A total of 40 061 cells with 10 cell types were obtained from the PFC of newborn mice in the 3 groups by scRNA-seq. The down-regulated genes in the PFC cells after single sevoflurane anesthesia were enriched in cell differentiation, forebrain neuron differentiation, noradrenergic neuron differentiation, and cerebral cortex GABAergic interneuron differentiation. The down-regulated genes after multiple sevoflurane anesthesia were enriched in positive regulation of cell differentiation. KEGG analysis showed that the down-regulated genes after single sevoflurane anesthesia were enriched in transforming growth factor-β signaling pathway, and the down-regulated genes after multiple sevoflurane anesthesia were enriched in the Notch signaling pathway. SCENIC analysis showed that early growth response 1 (Egr1) and SRY-box transcription factor 7 (Sox7) were up-regulated after both single and multiple sevoflurane anesthesia (both P<0.01), and HES family bHLH transcription factor 6 (Hes6) and NK2 homeobox 1 (Nkx2-1) were down-regulated only after single sevoflurane anesthesia (P<0.01). Activation of the gene set of the cell cycle in radial glial cells and neurons increased after sevoflurane anesthesia, and the increase in activation was more pronounced after multiple sevoflurane anesthesia. The gene set of the Hippo signaling pathway in neurons changed from inhibition to activation after multiple sevoflurane anesthesia. Subpopulation analysis of 8 224 neurons identified 8 neuronal lineage cells, and CytoTRACE scores indicated increased neuron stemness and delayed neuron development after sevoflurane anesthesia. The PFC neurons were divided into 3 developmental stages by pseudo-time analysis, and multiple sevoflurane anesthesia receded the differentiation of PFC neurons in pseudo-time (P=0.000). The down-regulated genes in PFC neurons of newborn mice after single sevoflurane anesthesia were enriched in the regulation of cyclin-dependent protein serine/ threonine kinase activity, mitotic cell cycle phase transition, cell differentiation, long-term memory, and G1/S transition of the mitotic cell cycle. The down-regulated genes in PFC neurons after multiple sevoflurane anesthesia were enriched in the negative regulation of cell population proliferation, positive regulation of cell differentiation, forebrain neuron differentiation, positive regulation of canonical Wnt signaling pathway, and cell differentiation. Conclusion ·Both single and multiple sevoflurane anesthesia promote PFC neuron proliferation and migration, and multiple sevoflurane anesthesia inhibits the differentiation of neural progenitor cell into neuron in PFC. The underlying mechanism might be related to cell cycle transitions.

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    Combined effects of intermittent fasting and thermogenic fat activation on the treatment and prevention of obesity in mice
    WU Kaimin, MA Jing, ZHAO Xuyun
    2023, 43 (9):  1131-1144. 
    doi: 10.3969/j.issn.1674-8115.2023.09.007

    Abstract ( 102 )   HTML ( 5 )   PDF (5768KB) ( 61 )  

    Objective ·To investigate the effects of intermittent fasting (IF) combined with thermogenic fat activation on the treatment and prevention of obesity in mice. Methods ·Male C57BL/6J mice aged 8 weeks were fed by high-fat diet for 4 months and then used as obesity treatment models. The prevention model was conducted on male and 8-week-old C57BL/6J mice. High-fat diet-induced obese mice and normal mice were respectively assigned into four groups: control group, alternate-day intraperitoneal CL316243 (β3-adrenergic receptor agonist,CL) injection group, IF group, and IF combined with alternate-day intraperitoneal CL injection group. Obesity treatment experimental mice and obesity prevention experimental mice were intervened for 38 d and 124 d, respectively, and they were all fed with high-fat diet during the intervention. The food intake and body weight were measured every two days. The blood glucose was measured at the end of the experiments. The brown adipose tissues (BAT), inguinal white adipose tissues (iWAT), epididymal white adipose tissues (eWAT), and livers were collected and weighed after the mice were sacrificed. The effect of IF combined with CL on morphologic changes was investigated by hematoxylin-eosin (H-E) staining. The expression levels of the genes related to thermogenesis, inflammation, and glucose and lipid metabolisms in the livers and adipose tissues were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Results ·In the treatment model, compared with IF alone, IF combined with CL further reduced the body weight and blood glucose of obese mice (P<0.05), reduced the lipid droplet size in the eWAT cells and the liver cells (P<0.05), promoted the expression levels of the thermogenic genes uncoupling protein 1 (Ucp1) and cell death inducing DFFA like effector α (Cidea) in the eWAT and the iWAT, and up-regulated the expressions of the fatty acid oxidation related genes in the eWAT and the iWAT, i.e., peroxisome proliferator-activated receptor α (Ppara) and enoyl-CoA hydratase and 3-hydroxyacyl CoA dehydrogenase (Ehhadh) (P<0.05). IF combined with CL also inhibited the expressions of inflammation-related genes in the eWAT and the liver (P<0.05) and promoted the expressions of glucose metabolism-related genes in the liver compared with the control group (P<0.05), but there were no significant differences compared with IF alone. In the prevention model, compared with IF alone, IF combined with CL further reduced the lipid droplet size in the eWAT cells and the iWAT cells, promoted the expression levels of Ucp1 and Cidea in the eWAT and the iWAT, and up-regulated the expression of Ppara and Ehhadh in the eWAT and the iWAT (P<0.05). IF combined with CL also resisted the weight gain induced by high-fat diet, improved blood glucose (P<0.05), and inhibited the expression levels of fatty acid oxidation-related genes in the liver compared with the control group (P<0.05), but there were no significant differences compared with IF alone. Conclusion ·Both in the obesity treatment and prevention models, IF combined with thermogenic fat activation can reduce lipidosis in the adipose tissue and promote the expression of thermogenic genes and fatty acid oxidation genes in the white adipose tissue compared with IF alone; however, the combined effects of them on body weight and blood glucose are superior to IF in the obesity treatment model, but not in the prevention model.

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    Clinical research
    Construction of Shanghai Diabetes Clinical Database and real-world study
    XUE Yanbin, QI Jiying, ZHANG Zizheng, JING Renjie, SUN Wen, YAO Huayan, HE Ping, CUI Bin, NING Guang
    2023, 43 (9):  1145-1152. 
    doi: 10.3969/j.issn.1674-8115.2023.09.008

    Abstract ( 258 )   HTML ( 12 )   PDF (3298KB) ( 164 )  

    Objective ·To construct a clinical database of diabetes in Shanghai, mine the value of clinical data, and carry out real-world study. Methods ·The data were extracted from Shanghai Link Healthcare Database. All original clinical data have undergone standard processes such as desensitization, encryption, cleaning, standardization, information extraction and structuring, and clinical data were analyzed by the method of medical statistics or machine learning according to different research contents. Results ·The database has imported the clinical data of 150 million visits and treatment records of 2.12 million diabetic patients in 37 municipal hospitals over a ten-year period from 2013 to 2022. The overall analysis showed the basic characteristics and development trends of all aspects of diabetes disease in real-world settings, the potential risks of diabetes are discovered by constructing retrospective cohort, and the inherent patterns of the disease are revealed by using machine learning methods such as cluster analysis and network analysis. Conclusion ·The establishment of Shanghai Diabetes Clinical Database can not only summarize and show the clinical status of diabetes, but also obtain more scientific achievements with realistic clinical value by real-world clinical data study.

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    Effect of somatic symptoms, anxiety and depression on clinical prognosis in patients with chronic heart failure
    LU Qifan, LIU Qiming, ZHOU Hongmei, CHAI Yezi, JIANG Meng, PU Jun
    2023, 43 (9):  1153-1161. 
    doi: 10.3969/j.issn.1674-8115.2023.09.009

    Abstract ( 90 )   HTML ( 9 )   PDF (1679KB) ( 59 )  

    Objective ·To explore the association of somatizatic symptoms, anxiety and depression with clinical prognosis in the patients with chronic heart failure (CHF). Methods ·The patients with CHF who visited the Department of Cardiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine from January 2018 to December 2021 were included. Demographic data and clinical features of the patients were collected. The Self-reported Somatic Symptom Scale of China (SSS-CN), the Patient Health Questionnaire-9 (PHQ-9), and the Generalized Anxiety Disorder-7 (GAD-7) were used to evaluate the patients′ conditions. Telephone follow-up was conducted at the 12th month after the first visit, and the specific information of the patients′ end-point events (including death, re-hospitalization, causes of death and re-hospitalization) was collected. Survival curve and Cox regression analysis were used to evaluate the clinical prognosis of the patients. Results ·A total of 195 patients were included. The SSS-CN scores in CHF patients were different between the two genders, among the different heart rate groups and the different cardiac function grades of New York Heart Association (NYHA), also between the patients with anxiety/depression or not (all P<0.05). Survival curve analysis showed that overall survival rate of patients in the moderate-severe somatic symptoms group was lower than that of the patients in the normal-mild group (Log rank P=0.020). Cox regression analysis showed that compared with the normal-mild group, the patients in the moderate-severe somatic symptoms group had a higher risk of all-cause death [hazard ratio (HR)=2.797, 95%CI 1.135-6.890]; the CHF patients with depressive symptoms had a higher risk of all-cause death (HR=2.883, 95%CI 1.150-6.984). Compared with the normal-mild group, the patients with moderate-severe somatic symptoms had a higher risk of cardiovascular death (HR=2.784, 95%CI 1.073-7.226). The CHF patients with depressive symptoms had a higher risk of cardiovascular death (HR=2.823, 95%CI 1.087-7.330). There were no statistically differences in anxiety, depression, somatization symptoms and their severity between all-cause hospitalization and hospitalization due to CHF. Conclusion ·The moderate-severe somatic symptoms and depression are the risk factors of all-cause death and cardiovascular death in the patients with CHF.

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    Radiomics-based left ventricular ejection fraction prediction: a feasibility study
    LIU Qiming, LU Qifan, CHAI Yezi, JIANG Meng, PU Jun
    2023, 43 (9):  1162-1168. 
    doi: 10.3969/j.issn.1674-8115.2023.09.010

    Abstract ( 78 )   HTML ( 7 )   PDF (2020KB) ( 49 )  

    Objective ·To assess the feasibility of using 3D imaging features extracted from cardiac magnetic resonance (CMR) short-axis cine images to predict left ventricular ejection fraction (LVEF). Methods ·A total of 100 left ventricular hypertrophy (LVH) patients who visited the Department of Cardiology, Renji Hospital, Shanghai Jiao Tong University School of Medicine from January 2018 to December 2021, as well as 100 healthy control (HC) subjects during the same period, were included. All subjects completed CMR examinations under the supervision of experienced cardiologists and radiologists. The endocardial and epicardial contours were then manually delineated by cardiologists. Measurements of cardiac function and morphology were completed and data was recorded, including LVEF, left ventricular end-diastolic volume (LVEDV), and left ventricular end-diastolic mass (LVEDM). Myocardial 3D radiomic features of CMR-cine sequences were extracted by the Pyradiomics package, and selected and sorted by using correlation coefficient and K-best method. The LVEF prediction was performed with linear regression (LR), random forest (RF) and gradient boost (GB) methods. Results were also compared with LVEF prediction based on clinical information and CMR parameters. Results ·In terms of clinical indicators, there were significant differences between the LVH and HC groups, such as LVEDV and LVEDM (all P<0.05); after extracting 3D radiomic features, the top 10 features were selected for further analysis. LR regression model, GB regression model and RF regression model were constructed for predicting the LVEF, and RF regression models showed the best results with seven features, in which the mean absolute error (MAE) was 0.066±0.002. Further comparison results showed that the model using radiomic information with CMR parameters (MAE=0.056±0.001) had the best performance and it was significantly better than the model using radiomic features (MAE=0.066±0.002) or CMR parameters (MAE=0.060±0.001) alone (both P<0.05). Conclusion ·The use of radiomic features for LVEF prediction has certain feasibility, and combining radiomic features with CMR parameters can further improve the prediction accuracy of the model.

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    Effect of intramuscular adipose tissue in the skeletal muscle of thigh on glucose metabolism in male patients with obesity
    LU Xiaobing, YUE Jiang, HE Shengyun, DONG Ying, LU Qing, MA Jing
    2023, 43 (9):  1169-1174. 
    doi: 10.3969/j.issn.1674-8115.2023.09.011

    Abstract ( 73 )   HTML ( 7 )   PDF (1309KB) ( 40 )  

    Objective ·To investigate the correlation between intramuscular adipose tissue (IMAT) content and glucose metabolism in male patients with obesity. Methods ·Eighty male patients with obesity were recruited from the Endocrinology Department of Renji Hospital, Shanghai Jiao Tong University School of Medicine from December 2019 to December 2020. According to the results of oral glucose tolerance test (OGTT), they were divided into normal glucose tolerance (NGT) group and impaired glucose regulation (IGR) group. General data and laboratory test indicators of the two groups were collected and compared. mDixon-Quant technique was used to measure the IMAT content in each skeletal muscle of the thigh in the two groups, and the proton density fat fractions (PDFF) of skeletal muscle in the two groups were compared. The multivariate Logistic regression model was used to analyze the independent influencing factors of IGR occurrence. Results ·Compared with the NGT group, patients in the IGR group had a larger waist circumference (P=0.017), higher glutamic-pyruvic transaminase level, glutamic-oxaloacetic transaminase level, γ-glutamyl transferase (GGT) level, triacylglycerol (TAG) level, nonestesterified fatty acid (NEFA) level and sartorius PDFF (all P<0.05). After adjusting for confounding factors such as age, body mass index, GGT, TAG and NEFA, the results of multivariate Logistic regression analysis showed that PDFF of vastus lateralis, semitendinosus and sartorius were the risk factors for IGR (all P<0.05). Conclusion ·Higher levels of IMAT content in vastus lateralis, semitendinosus and sartorius will increase the risk of IGR in male patients with obesity.

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    Evidence-based medicine
    Diagnostic value of cell-free DNA to biliary tract cancers: a meta-analysis
    YANG Yue, HE Kaiju, ZONG Jiahao, YANG Ziyi, WU Xiangsong, GONG Wei
    2023, 43 (9):  1175-1185. 
    doi: 10.3969/j.issn.1674-8115.2023.09.012

    Abstract ( 90 )   HTML ( 7 )   PDF (4019KB) ( 66 )  

    Objective ·To comprehensively evaluate the diagnostic accuracy of cell-free DNA (cfDNA) to biliary tract cancer (BTC), and provide a basis for better clinical application. Methods ·Clinical studies on the diagnostic value of cfDNA to BTC were collected by searching eight databases from inception to April 2023. The studies were selected according to the inclusion and exclusion criteria, and then data was extracted. The threshold effects were assessed with Spearman′s rank correlation analysis, and heterogeneity among the included studies was analyzed by using Cochran′s Q test and I2 test. A bivariate mixed-effects model was fitted, and statistics such as overall sensitivity, specificity, and area under the curve (AUC) were calculated to determine the diagnostic performance. The subgroup analyses were carried out based on the study type, sample size, detection method, sample source, and diagnostic reference standard. Results ·A total of 28 diagnosis tests were included, all of which were evaluated as medium-high quality by using Diagnostic Accuracy Studies Tool Version 2 (QUADAS-2). The presence of threshold effects was found by using the Spearman rank correlation analysis. The pooled sensitivity was 0.80 (95%CI 0.67?0.88), and specificity was 0.96 (95%CI 0.92?0.98), positive likelihood ratio (PLR) was 22.7 (95%CI 9.4?55.2), negative likelihood ratio (NLR) was 0.21 (95%CI 0.12?0.36), and diagnostic odds ratio (DOR) was 108 (95%CI 31?374), respectively. The AUC of the summary receiver operating characteristic (SROC) curve was 0.96 (95%CI 0.94?0.98), demonstrating the high accuracy of cfDNA in the diagnosis of BTC. The results of subgroup analyses suggested that the accuracy and sensitivity of choosing different testing methods and sample sources varied. Conclusion ·The detection of cfDNA has high sensitivity and specificity in diagnosing BTC, and is suitable for the patients suspected to be malignant after screening with imaging tests and conventional tumor markers. However, the standardization and uniformity of detection methods and sample sources still need to be further standardized by conducting clinical studies on a wider population.

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    Clinical nursing
    Latent profile analysis of adverse effects associated with endocrine therapy in prostate cancer patients based on the theory of unpleasant symptoms
    ZHU Hanjing, YIN Hongfan, YOU Sijie, YANG Yan
    2023, 43 (9):  1186-1193. 
    doi: 10.3969/j.issn.1674-8115.2023.09.013

    Abstract ( 85 )   HTML ( 10 )   PDF (1612KB) ( 39 )  

    Objective ·Based on the theory of unpleasant symptoms, to investigate the current status of adverse effects associated with endocrine therapy in prostate cancer patients, and identify the difference of population specificity in each latent category. Methods ·From June 2022 to September 2022, 274 patients with endocrine therapy for prostate cancer in the Urology Department of Renji Hospital, Shanghai Jiao Tong University School of Medicine were selected by convenience sampling method. Adverse reactions associated with endocrine therapy were investigated by basic information questionnaire and simplified Chinese version of the aging male′s symptoms scale. Latent profile analysis was conducted and the differences of population characteristics among categories were assessed based on t-test, variance analysis and multiple Logistic regression. Perform latent profile analysis was performed by using Mplus 8.3 to identify latent classes of endocrine treatment-related adverse events in prostate cancer patients. Results ·Adverse reactions associated with endocrine therapy in patients with prostate cancer could be divided into three groups: mild-symptom group (n=96, 35.0%), moderate-symptom group (n=111, 40.5%) and severe-symptom group (n=67,24.5%). Compared to patients with mild symptoms, those in the moderate-symptom group had significant differences in psychosocial adaptation (OR=1.038, 95%CI 1.018?1.060, P=0.000), and whether genetic detection was performed (OR=0.336, 95%CI 0.129?0.879, P=0.026). Compared to patients with mild symptoms, those in the severe-symptom group had significant differences in psychosocial adaptation (OR=1.027, 95%CI 1.003?1.051, P=0.024), disease uncertainty (OR=1.021, 95%CI 1.005?1.038, P=0.011), M stage (OR=0.354, 95%CI 0.136?0.924, P=0.034), and prostate specific antigen (PSA) (OR=0.142, 95%CI 0.042?0.480, P=0.002; OR=0.275, 95%CI 0.083?0.914, P=0.035). Conclusion ·The incidence of adverse reactions associated with endocrine therapy for prostate cancer is high. Adverse effects associated with endocrine therapy in prostate cancer patients can be classified into three categories. There are significant differences in disease metastasis, PSA levels, genetic testing, disease uncertainty, and psychosocial adaptation among prostate cancer patients receiving endocrine therapy in different categories. Healthcare professionals should assess the diverse sociodemographic background, disease-specific factors, and psychosocial status of prostate cancer patients receiving endocrine therapy, and provide targeted support according to their characteristics to help them acquire self-management skills and cope with adverse treatment effects proactively, in line with the precision medicine framework.

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    Reliability and validity of the Chinese version of St Andrew′s Nutrition Screening Instrument
    ZHOU Shuang, LU Huijie, DU Zheyi, HU Shimin, DONG Ping, JIANG Ying
    2023, 43 (9):  1194-1200. 
    doi: 10.3969/j.issn.1674-8115.2023.09.014

    Abstract ( 95 )   HTML ( 7 )   PDF (1383KB) ( 69 )  

    Objective ·To translate St Andrew′s Nutrition Screening Instrument (SANSI), and test its reliability and validity. Methods ·With the consent of the authors, the SANSI was translated into Chinese in accordance with the "Brislin translation-back translation method" and the Chinese version underwent cross-cultural debugging. Five clinical medical staff were selected to a pre-survey on 10 patients, and the expression and structure of the scale items were fine-tuned according to the feedback. A total of 221 inpatients with mental disorders were selected by convenient sampling method in Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine as research objects from January to February 2022, and the general clinical data of these patients were collected. The correlation between the items in Part Ⅲ and the identified risks in that part was evaluated by Spearman correlation analysis, and some items were deleted according to the results. Eight experts in mental disorders or nutrition were selected to evaluate the items of Chinese version of SANSI, and then the content validation indexes (CVIs) were calculated. With the standard of Nutritional Risk Screening 2002 (NRS2002), Spearman correlation analysis was used to evaluate the calibration validity of Chinese version of SANSI. Cronbach′s α coefficient, split half reliability and inter-rater reliability (κ consistency coefficient) were used to evaluate the reliability of the Part Ⅲ of the scale. Results ·Through literal translation, back translation, cross-cultural debugging and pre-investigation, Chinese version of SANSI was formed. Among the 221 patients with mental disorders, 174 (78.73%) were males, the mean age was (64.12±13.87) years, and the duration of diseases was (26.06±17.65) years. There were 128 cases of schizophrenia (57.92%), 75 cases of organic mental disorders (33.94%), 10 cases of mood disorders (4.52%) and 8 cases of other mental disorders (3.62%). According to the results of correlation analysis in Part Ⅲ, the original items 1, 3, and 10 were deleted. The correlation coefficients between the remaining 7 items and the risk degree in this part were 0.391-0.734 (all P<0.01), which were retained. The item-level CVIs of Chinese version of SANSI ranged from 0.88 to 1.00, and the scale-level CVI was 0.95. The calibration validity of the scale with NRS2002 was 0.400 (P<0.01). The Cronbach′s α coefficient for Part Ⅲ was 0.759 and the split half reliability was 0.747. The κ consistency coefficient of 2 nurses using Chinese version of SANSI in the same group of 50 patients was 0.886 (P>0.05). Conclusion ·Chinese version of SANSI has good reliability and validity for hospitalized patients with mental disorders.

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    Current status and influencing factors of early mobilization of patients undergoing laparoscopic radical resection of colorectal cancer
    LUO Chen, SHEN Ling, WANG Chuanwei, GU Jiani, WANG Jin, ZHAO Li, HUANG Shuai
    2023, 43 (9):  1201-1210. 
    doi: 10.3969/j.issn.1674-8115.2023.09.015

    Abstract ( 78 )   HTML ( 8 )   PDF (1911KB) ( 83 )  

    Objective ·To investigate the status of early mobilization and influencing factors of the patients undergoing laparoscopic radical resection of colorectal cancer (CRC). Methods ·The convenience sampling method was used to select patients undergoing laparoscopic radical resection of CRC in the Department of Colorectal Surgery and Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine from January to December, 2022. The patients′ general information, disease-, surgery- and postoperation-related information, and the situation of postoperative early mobilization were collected by bedside interview and electronic medical record system at 24 h, 48 h and 72 h after surgery. The influencing factors were analyzed by univariate analyses and binary Logistic regression. Results ·A total of 277 patients were included. Within 24 h after surgery, 47 patients got out of bed with the early mobilization rate of 16.97%. The walking distance of these patients was 55.46 (18.28, 145.60) m within 24 h after surgery, with a minimum of 2.60 m and a maximum of 803.68 m. The average scores of Brown rating of mobility within 24 h, >24-48 h, and >48-72 h after surgery were 2 (0, 4) points, 8 (0, 10) points, and 8 (8, 10) points, which respectively belonged to the low level, moderate level, and moderate level. There were statistical differences in age, preoperative hemoglobin level, anesthesia duration, and the number of indwelling catheters between the early mobilization group and the non-early mobilization group (all P<0.05). Initial exhaust time, initial defecation time and postoperative length of stay of the early mobilization group were significantly shorter than those of the non-early mobilization group (all P<0.05). There were no postoperative complications in the early mobilization group, while the postoperative complications occurred in 11 patients in the non-early mobilization group with the incidence of complications of 4.78%. Binary Logistic regression analysis showed that age≥70 years old, low preoperative hemoglobin level and long anesthesia duration had significant influence on postoperative early mobilization (all P<0.05). Conclusion ·Early mobilization of patients after laparoscopic radical resection of CRC can significantly accelerate postoperative rehabilitation, but the current status of early mobilization needs to be improved. Age, preoperative hemoglobin level and anesthesia duration are influencing factors of early mobilization.

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    Forum
    Analysis on the existing problems and improving approaches to the clinical research talents team cultivation in China
    LI Dongliang, WANG Suping, HE Hao, WANG Bingshun, ZHOU Liang
    2023, 43 (9):  1211-1218. 
    doi: 10.3969/j.issn.1674-8115.2023.09.016

    Abstract ( 67 )   HTML ( 6 )   PDF (2502KB) ( 41 )  

    Objective ·To investigate the current situation and problems of the construction of clinical research talents team in China, and propose targeted improvement strategies. Methods ·Self-designed questionnaires were made after literature review, expert interviews and two rounds of Delphi. An online questionnaire survey was conducted on 583 clinical research-related personnel from hospitals, biomedical enterprises, medical colleges and government departments in 27 provinces, cities and autonomous regions, and the survey results were analyzed. Results ·A total of 583 questionnaires were collected, 579 of which were valid, with an effective rate of 99.3%. The research results showed that: ① The lack of clinical research talents and the poor development environment of talents were the key factors restricting the high-level clinical research in China. ② Among the respondents, 72.7% of them were dissatisfied (very dissatisfied, dissatisfied and average) with the current training of clinical research talents. The main problems included lack of high-level research talents and a professional support team; the current performance evaluation system was monotonous, the salary and incentive were not profitable for clinical research, and medical personnel engaged in clinical research and support staff lacked promotion channels, etc. ③ The improvement strategies included systematically improving the clinical research ability of medical personnel, improving the clinical research training curriculum system, adopting different training methods in the school education stage and in-service education stage, and attaching more importance to the two teams′ training, clinical research physicians and clinical research methodology professionals. Conclusion ·Currently, it is urgent to expand the number of excellent medical students and improve the courses of clinical research methodology and relevant laws and regulations, encourage experienced research-oriented doctors to guide new staff in research projects, systematically improve the scientific research ability of current medical personnel, pay more attention to training of standardized implementation of clinical research projects, topic selection design and others, gather a high-level team of composite clinical research medical personnel, increase the amount of professionals in clinical research methodology, further attach importance to clinical research, and improve the development environment of clinical research talents from the aspects of professional title promotion, salary, scientific research evaluation, etc, so as to improve the level of clinical research in China.

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