1. Using aptamer of sgc8 for diagnosis of acute leukemia
Journal of Shanghai Jiaotong University(Medical Science) 2020;40(9):1157-1167
Objective : To study the ability of aptamer sgc8 to recognize different bone marrow cells and evaluate its diagnostic value for acute leukemia (AL). Methods : 5-Carboxyfluorescein-labeled aptamer sgc8 and its control random library chain (Lib) were used to examine 83 clinical bone marrow samples by flow cytometry, and the difference between sgc8 and Lib of the positive percentages of each cell population was analyzed. Kruskal-Wallis test was used for statistical analysis. Results : In AL samples, sgc8 has a specific ability to recognize tumor cells in most of the acute T-cell acute lymphoblastic leukemia (T-ALL) and acute myeloid leukemia (AML) samples, and the ability of sgc8 to recognize tumor cells of various AML subtypes is different while there is no difference for the ability to recognize tumor cells of T-ALL subtypes. But sgc8 doesn't show obvious recognition ability in acute B-cell lymphoblastic leukemia (B-ALL) samples. In normal bone marrow samples, sgc8 can specifically recognize the myeloid blast cellsbut not early B cells and other mature cell populations. Conclusion : The aptamer sgc8 has specific recognition ability in AML, T-ALL and normal bone marrow samples, and may have different diagnostic values for various AML subtypes, but it does not significantly recognize cells of B-ALL samples.
2. Gonadotropin-releasing hormone-antagonist up-regulate the proportion of uterine natural killer cells and enhance their toxicity during the implantation window period of mice
Journal of Shanghai Jiaotong University(Medical Science) 2020;40(9):1168-1173
Objective: To investigate the effects of gonadotropin-releasing hor-mone-antagonist (GnRH-ant) on the proportion and toxicity of mice uterine nature killer (uNK) cells during implantation window. Methods: Sixteen C57BL/6 mice were randomly divided into GnRH-ant group and control group, with 8 mice in each group. From the 3rd day of the estrous cycle, GnRH-ant (1.5 μg/100 g) was injected intraperitoneally into the mice of the GnRH-ant group for 7 days continuously, and the control group was injected with the same volume of normal saline at the same time point. On the 7th day, the mice of the two groups were injected with human menopausal gonadotropin (40 U/100 g). The next day, they were injected with human chorionic gonadotropin (100 U/100 g) and sacrificed after 48 h. The uterus tissues were taken out for primary digestion to obtain single-cell suspension. Flow cytometry was used to analyze the proportion of uNK cells and the expression levels of toxicity molecules perforin (Pf) and granzyme B (Gz-B). Results: Compared with the control group, the proportion of uNK cells in GnRH-ant group increased (P=0.000), the proliferation level increased (P=0.000), the apoptosis level decreased (P=0.004), and the expression of toxicity molecules Pf (P=0.000) and Gz-B (P=0.034) were up-regulated. Conclusion: GnRH-ant may up-regulate the proportion of uNK cells and enhance their toxicity in the implantation window period of mice.
3. Bioinformatics analysis of miRNAs in mild cognitive impairment due to Alzheimer's disease
Journal of Shanghai Jiaotong University(Medical Science) 2020;40(9):1174-1183
Objective: To analyze the expression profile of plasma microRNA (miRNA) in patients with mild cognitive impairment (MCI) due to Alzheimer's disease (AD) by bioinformatics method, and explore its pathogenesis at the level of genetic regulation. Methods: Five MCI patients due to AD and five control participants were recruited. The plasma miRNA expression profiles were analyzed by miRNA microarray sequencing. Target genes of significantly up-regulated miRNAs were detected by TargetScan 7.2 database. The miRNA-gene interaction network of significantly up-regulated miRNAs was established by Cytoscape software, and the key miRNAs of the network were analyzed. The target genes of key miRNAs were analyzed by Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis using R packages. Results: There are 13 up-regulated miRNAs in the plasma of MCI patients due to AD, and 5 of them were key miRNAs in miRNA-gene interaction network. Target genes of these miRNAs were mainly involved in biological process such as synaptic plasticity reg-ulation, Wnt signaling pathway, synaptic vesicle transport and synaptic vesicle localization, as well as Ras signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway and glycolysis/gluconeogenesis pathway. Conclusion: Five up-regulated miRNAs in plasma of MCI due to AD may be the main regulators involved in the pathological mechanism of AD, which can be used as potential biomarkers for diagnosis of MCI due to AD.
4. Injectable hydrogel loaded with bone morphogenetic protein-2 microspheres for bacteriostasis and osteogenesis
Journal of Shanghai Jiaotong University(Medical Science) 2020;40(9):1184-1192
Objective: To construct a novel antibacterial and injectable hydrogel (BMP/Gel/SH-Ag) loaded with bone morphogenetic protein-2 (BMP-2) microspheres, and investigate its biocompatibility, antibacterial properties and bone-promoting properties. Methods: The photocrosslinked gelatin microspheres loaded with BMP-2 were prepared by microfluidics. The microspheres were mixed with 4-arm thiol-terminated poly (ethylene glycol) (4SH-PEG) and crosslinked with Ag+ to prepare injectable sulfhydrylated PEG hydrogels (BMP/Gel/SH-Ag). The micromorphology of microspheres and hydrogels was observed by light microscope and scanning electron microscope. The drug release profile was investigated at 37℃ in a shaker (100 r/min). The injectability of BMP/Gel/SH-Ag was evaluated by injecting hydrogel using a syringe with a tip diameter of 0.5 mm. The antibacterial activity of BMP/Gel/SH-Ag against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) was evaluated by agar diffusion test. The biocompatibility of BMP/Gel/SH-Ag was verified by CCK-8, and the bone-promoting activity was evaluated by alkaline phosphatase (ALP) assay and calcium nodule staining in bone marrow mesenchymal stem cells (BMSCs). Results: Gelatin microspheres had smooth appearance and uniform particle size distribution (~ 350 μm). BMP/Gel/SH-Ag had porous micro-structure and can be injected with a syringe needle with a diameter of up to 0.5 mm in diameter to produce hydrogel filament. The cumulative release of BMP-2 from BMP/Gel/SH-Ag was (81.8±3.6)% after being incubated for 8 d. BMP/Gel/SH-Ag had obvious inhibitory effect on S. aureus and E. coli. CCK-8 results showed that BMP/Gel/SH-Ag had good biocompatibility. BMP/Gel/SH-Ag can increase the expression of ALP and the content of calcium nodules in rat BMSCs. Conclusion: The BMP/Gel/SH-Ag has good performance in promoting osteogenesis and an-ti-infection.
5. Expression of lnc-MTBP-5 in colorectal cancer and its effect on cell invasion
Journal of Shanghai Jiaotong University(Medical Science) 2020;40(9):1193-1201
Objective: To analyze the expression of lnc-MTBP-5 in colorectal cancer (CRC), and explore the effect of lnc-MTBP-5 on the invasion of CRC cells and its potential mechanism. Methods: Bioinformatics data from PRJNA218851 and PRJNA376161 data sets were extracted from the Sequence ReadArchive (SRA) database to screen CRC metastasis associated lncRNAs. The Cancer Genome Atlas (TCGA) was used to analyze the expression of lnc-MTBP-5 in CRC tissues and normal tissues, its relationship with the prognosis of patients, and its correlation with metastasis related factors. Quantitative real-time PCR (qPCR) was used to detect the expression of lnc-MTBP-5 in normal intestinal epithelial cells and CRC cells, as well as 53 CRC tissues and para-cancer mucosa. After lnc-MTBP-5 was down-regulated in CRC cells, CCK-8 assay, clone formation and Transwell assay were performed to observe the effect of lnc-MTBP-5 on the proliferation and invasion ability of CRC cells. Results: Lnc-MTBP-5 was associated with CRC metastasis. The expression of lnc-MTBP-5 was significantly increased in 5 CRC cell lines and CRC tissues. Compared with patients with low expression of lnc-MTBP-5, CRC patients with high expression of lnc-MTBP-5 were younger, had higher American Joint Committee on cancer (AJCC) staging, and were prone to metastasis. Lnc-MTBP-5 was positively correlated with CRC metastasis associated in colon cancer 1 (MACC1), mesenchymal to epithelial transition factor (MET) and cadherin-associated protein. After lnc-MTBP-5 was down-regulated, the invasion ability of CRC cells decreased. Conclusion: Lnc-MTBP-5 is up-regulated in CRC cell lines and CRC tissues, and it is negatively correlated with the prognosis of patients. Lnc-MTBP-5 can promote the invasion ability of CRC cells, which may be related to MACC1-HGF (hepatocyte growth factor)/MET pathway.
6. Inhibitory effect of toosendanin on gastric cancer cells BGC-823 by downregulating circDLST
Journal of Shanghai Jiaotong University(Medical Science) 2020;40(9):1202-1206
Objective: To investigate the effect of toosendanin (TSN) on the growth and invasion of gastric cancer cells BGC-823 by regulating circDLST expression. Methods: After gastric cancer cells BGC-823 were exposed to different con-centrations of TSN (0, 0.5, 1.0, and 2.0 μmol/L) for 24 h, quantitative PCR was used to detect the expression of circDLST. BGC-823 cells were transfected with the circDLST overexpression lentiviral vector or its control vector (CON), and then treated with 0.5 μmol/L TSN or PBS. So the cells were divided into circDLST+TSN group, CON+TSN group and CON+PBS group. The viability and invasive potential of BGC-823 cells were observed by MTT proliferation test and Transwell invasion assay. The subcutaneous transplanted tumor models were established by using circDLST-transfected cell line BGC-823 or the control cell line in nude mice, and then 200 μg/kg TSN or the same volume of PBS was injected intraperitoneally every day. So the mice were divided into circDLST+TSN group, CON+TSN group and CON+PBS group. Results: Compared with the control group (0 μmol/L), all 3 concentrations of TSN decreased the expression levels of circDLST in a concentration dependent manner (P<0.01). TSN could significantly reduce the cell viability, cell invasion and subcutaneous xenograft tumor growth (P=0.000), while circDLST overexpression reversed the inhibitory effect of TSN (P<0.01). Conclusion: TSN may inhibit the growth and invasion of gastric cancer cells BGC-823 by downregulating circDLST expression.
7. Analysis of the feature and influencing factors of anhedonia in schizophrenia
Journal of Shanghai Jiaotong University(Medical Science) 2020;40(9):1207-1212
Objective: To explore the feature and influencing factors of anhedonia in schizophrenia. Methods: A total of 71 schizophrenia patients and 50 healthy controls were recruited during December 2018 and December 2019. Positive and Negative Syndrome Scale (PANSS) was used for assessing psychotic symptoms. Temporal Experience of Pleasure Scale (TEPS) and Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were applied to the evaluation of anhedonia and cognitive function respectively for each subject. Results: The evaluation result of TEPS showed both anticipatory and consummatory pleasure scores were lowered in patients with schizophrenia than those in healthy people (P=0.000). Stepwise linear regression analysis showed that negative subscale score of PANSS (B=-0.895, P=0.002) and delayed memory score of RBANS (B=0.265, P=0.001) were associated with anhedonia in schizophrenia. Conclusion: Patients with schizophrenia exhibit anticipatory and consummatory anhedonia, both of which are influenced by negative symptoms and delayed memory in schizophrenia.
8. Value of transformation zone type in the evaluation of random biopsy among patients without visible lesions under colposcopy
Journal of Shanghai Jiaotong University(Medical Science) 2020;40(9):1213-1217
Objective: To explore the value of cervical transformation zone (TZ) type in assessing whether a random biopsy should be used to diagnose high-grade squamous intraepithelial lesion (HSIL) among patients without visible lesions under colposcopy. Methods: A total of 517 patients who underwent colposcopy (without visible lesions) due to high risk subtype infection of human papillomavirus (HPV) or thinprep cytologic test (TCT) abnormality were enrolled. TZ types were identified, random biopsies were performed, and the value of TZ type, Ⅱand III in the diagnosis of HSIL was evaluated. Results: There were 517 cases without visible lesions under colposcopy. Three hundred and ninety-six of them were TZ type III, and the detection rate of HSIL was 3.8% (15/396) by random biopsy, while one hundred and twenty one of them were TZ type and Ⅱ, and the detection rate of HSIL was 8.3% (10/121). Compared with the TZ type III, the detection rate of HSIL in the TZ type and Ⅱ was significantly increased (P=0.000). Logistic regression showed that TCT abnormality, TZ type and Ⅱ were the risk factors for HSIL detection in patients without visible lesions under colposcopy. Conclusion: Random multipoint biopsy can significantly increase detection rate of cervical HSIL when no visible lesion is visualized under colposcopy, particularly in women with abnormal TCT results or TZ type and Ⅱ.
9. Clinical value of domestic electromagnetic navigation system for precutaneous transthoracic needle biopsy: a randomized controlled trial
Journal of Shanghai Jiaotong University(Medical Science) 2020;40(9):1218-1221
Objective: To evaluate the clinical value of the electromagnetic navigation system for precutaneous transthoracic needle biopsy. Methods: A prospective randomized controlled trial was carried out. One hundred and thirteen patients who needed to have lung nodule biopsy were divided into two groups according to the random number table: the auxiliary puncture group (n=57) adopting the electromagnetic navigation system for precutaneous transthoracic needle biopsy, and the conventional operation group (n=56) adopting the traditional CT-guided transthoracic needle biopsy. The operation process of the two groups was completed by junior doctors under the supervision and guidance of senior doctors. The time of puncture, the number of CT scan, and postoperative complications were observed and compared between the two groups. Results: There was no significant difference in operation time between the auxiliary group and the conventional group [(26.7±8.0) min vs (25.0±7.8) min, P=0.261)]. There was no significant difference in the number of CT scan between the two groups (4.9±2.7 vs 5.1±2.7, P=0.810). There was no significant difference in the incidence rate of pneumothorax (15.8% vs 19.6%, P=0.592) and bleeding (17.5% vs 14.3%, P=0.636) between the two groups. Conclusion: The domestic elec-tromagnetic navigation system for precutaneous transthoracic needle biopsy can safely and effectively assist clinicians to complete lung biopsy.
10. Prediction of functional connectivity of fronto-limbic network in the outcome of subjects with clinical high-risk for psychosis
Journal of Shanghai Jiaotong University(Medical Science) 2020;40(9):1222-1228
Objective: To explore the role of functional connectivity (FC) within the fronto-limbic network in predicting the onset of psychosis in the subjects with clinical high-risk for psychosis (CHR). Methods: A total of 164 CHR subjects and 89 healthy controls (HC) who underwent resting-state functional MRI were recruited. FCs between frontal [medial prefrontal cortex and bilateral or-bitofrontal cortex (OFC)] and limbic (bilateral hippocampus and bilateral amygdala) brain regions at baseline were calculated. CHR subjects were further divided into 3 subgroups, i.e., CHR converters (CHR-C) group, symptomatic CHR (CHR-S) group and remitted CHR (CHR-R) group according to clinical outcome after one-year follow-up. The FCs of fronto-limbic network were compared between the groups and among the subgroups, and their interaction with brain regions, as well as their correlations with positive and negative symptoms were analyzed. Results: There was no significant main effect of group (P=0.110), but a significant interaction of subgroups and brain regions (P=0.049). CHR-C group had lower FC between bilateral OFC and bilateral amygdala than HC group and CHR-R group (all P<0.05). The FCs between left OFC and left hippocampus in the three CHR subgroups were all lower than that in HC group (all P<0.05). In addition, the FC between left OFC and right amygdala was positively correlated with the severity of negative symptoms in CHR-C group, while the FCs between left OFC and bilateral hippocampus and between right OFC and left hippocampus were negatively correlated with the severity of positive symptoms in CHR-C group. Conclusion: The decrease of OFC-hippocampus connectivity may be common in the subjects with CHR, while the decrease of OFC-amygdala connectivity may predict CHR subjects will convert to schizophrenia in the later stage.