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    Whole-brain inputs mapping to the projection neurons in laterodorsal thalamic nucleus innervating primary visual cortex in mice
    Li-zhao WANG, Guo-fen MA, Yan-mei LIU, Yan-jie WANG, Zi-yue WANG, Zhao-nan CHEN, Si-yu ZHANG, Tian-le XU
    2021, 41 (6):  701-709. 
    doi: 10.3969/j.issn.1674-8115.2021.06.001

    Abstract ( 142 )   HTML ( 174 )   PDF (12693KB) ( 51 )  
    Objective

    ·To analyze the whole-brain inputs to the projection neurons in the lateral dorsal nucleus (LD) of thalamus innervating primary visual cortex (V1) in mice.

    Methods

    ·The adeno-associated virus (AAV) vectors expressing the fusion protein of wheat germ agglutinin and Cre recombinase (Cre) were injected into V1 of C57BL/6J male mice, and the AAV vectors with Cre-inducible expression of avian sarcoma/leukosis virus envelope glycoprotein receptor TVA and rabies glycoprotein were injected into LD, respectively. Twenty-eight days later, the pseudotyped rabies virus (RV) was injected into V1. After the full expression of RV-mediated green fluorescent protein in the infected input neurons of LD, i.e., 7 d later, brain samples were collected and frozen sections were made. The whole-brain distribution of RV-labeled neurons were observed under fluorescence microscope, and quantitative analysis was performed by using high-throughput anatomical data analysis software.

    Results

    ·Through fluorescence microscope and quantitative analysis, the whole-brain map showed that the inputs of LD neurons innervating V1 mainly came from cortex, middle brain and inter brain, accounting for (58.1±4.8)%, (23.2±0.9)% and (15.3±4.0)% of the total number of GFP-labeled neurons in the whole brain, respectively. In the cortex, the areas with the most input neurons were somatomotor area, visual area and somatosensory area. A large number of input neurons were also distributed in prefrontal cortex and medial commissural cortex. In the sensory cortex, the cell bodies of the inputs were mainly distributed in the fifth and sixth layers.

    Conclusion

    ·The direct inputs of LD neuron subgroups innervating V1 in mice are widely distributed throughout the brain, most of which are located in the cortex.

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    Basic research
    Suppressing effect of the Na+/Ca2+ exchanger blocker CB-DMB on the growth of human glioblastoma cells
    Jing-jing LIU, Hui-jie HU, Zi-kai LIU, Ming-ke SONG
    2021, 41 (6):  710-716. 
    doi: 10.3969/j.issn.1674-8115.2021.06.002

    Abstract ( 182 )   HTML ( 168 )   PDF (2296KB) ( 49 )  
    Objective

    ·To test the inhibitory effect of the Na+/Ca2+ exchanger (NCX) blockers on the growth of human glioblastoma cells.

    Methods

    ·Human glioblastoma cell lines (U87, U251 and SF188) and human astrocytes were cultured in vitro. The cells were treated with NCX blockers SN-6, YM244769, SEA0400, CB-DMB and the chemotherapeutic agent temozolomide (TMZ). SN-6, YM244769 and SEA0400 were selective inhibitors for the reverse operation of NCX; while CB-DMB was NCX bidirectional blocker, but preferentially blocked the forward mode of NCX. The TMZ was used as a reference drug. Cell counting kit-8 (CCK-8) assay was used to quantify and assess the cell viability, and half maximal inhibitory concentration (IC50) of the drug was obtained. Calcium imaging was used to detect the changes of Ca2+ signal in U87 cells treated with NCX inhibitors, and Western blotting was used to detect the expression of mitogen-activated protein kinase (MAPK) signaling pathway proteins. Cellular apoptosis was evaluated by flow cytometry assay.

    Results

    ·CCK-8 results showed that direct application of the NCX bidirectional blocker CB-DMB to glioblastoma cell lines (U87, U251 and SF188) for 48 h caused a dose-dependent growth inhibition with IC50 values of 2.06, 2.19 and 1.82 μmol/L, respectively. In contrast, NCX reverse blockers SN-6, YM244769 and SEA0400 had no significant effect on the growth activity of glioblastoma cells. CB-DMB had little effect on the growth activity of human astrocytes. Calcium imaging and Western blotting results confirmed that CB-DMB blocked the forward transport mode of NCX to elevate intracellular Ca2+, causing intracellular calcium overload and then inducing apoptosis of U87 cells and activating MAPK signaling pathway. Flow cytometry assay results showed that the rate of apoptosis induced by CB-DMB in glioblastoma cells was much faster than that induced by TMZ (P=0.002). The combination of CB-DMB and TMZ enhanced the inhibitory effect of TMZ on the growth of tumor cells.

    Conclusion

    ·The inhibitory effect of CB-DMB on the growth of human glioblastoma cells may be related to blocking the forward transport mode of NCX. The plasma membrane NCX is a potential new target for the treatment of human glioblastoma.

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    Impact of Ras association domain family 5 on cell migration and invasion of head and neck squamous cell carcinoma
    Yu-sheng LU, Wen-yi YANG, Hai-long MA, Jing-zhou HU
    2021, 41 (6):  717-723. 
    doi: 10.3969/j.issn.1674-8115.2021.06.003

    Abstract ( 143 )   HTML ( 171 )   PDF (4573KB) ( 48 )  
    Objective

    ·To investigate the effect of Ras association domain family 5 (RASSF5) on migration and invasion of head and neck squamous cell carcinoma (HNSCC).

    Methods

    ·The expression of RASSF5 gene in 563 cases of HNSCC from the Cancer Genome Atlas (TCGA) database and the effect of RASSF5 expression on prognosis and survival of patients were analyzed by Gene Expression Profiling Interactive Analysis (GEPIA) platform. The lentivirus overexpressing RASSF5 (LV RASSF5) and control lentivirus (LV vector) were constructed by CMV-MCS-PGK-Puro vector. The wound-healing assay and the Transwell assay were performed to test the invasion and metastasis capacity of overexpressed-RASSF5 HNSCC cells. In addition, the expressions of epithelial cadherin (E-cadherin), Snail, glycogen synthase kinase 3β (GSK-3β) and phosphorylated GSK-3β (p-GSK-3β) were determined by Western blotting in RASSF5-overexpressed HNSCC cells. The lung metastasis model of HNSCC in 10 BALB/c nude mice were established. Cal27, which were transfected with LV RASSF5 or LV vector, were respectively injected into 5 BALB/c nude mice via tail vein, and the quantity of metastasis nodules was counted to evaluate the effect of RASSF5 overexpression on tumor metastasis ability.

    Results

    ·In HNSCC, the gene expression level of RASSF5 was lower than that in normal tissues (P=0.001). Patients with lower gene expression of RASSF5 had worse overall survival (P=0.005) and disease-free survival (P=0.004). The relative healing areas of Cal27 and HN30 transfected with LV RASSF5 were higher than those of the control group (transfected with LV vector) at the experimental endpoint of the wound-healing assay (P=0.015, P=0.003). The number of cells that had traversed the cell-permeable membrane was higher in Cal27 and HN30 cells transfected with LV RASSF5 than those in the control group in the Transwell migration assay (P=0.005, P=0.001). And in the Transwell invasion assay, the number of invaded cells that had traversed the matrigel-coated membrane was also higher in Cal27 and HN30 cells transfected with LV RASSF5 than those in the control group (P=0.001, P=0.001). Western blotting showed an increased level of E-cadherin, and decreased level of Snail and p-GSK-3β/GSK-3β ratio in RASSF5 overexpression Cal27 and HN30 cells. And in the metastasis assay of BALB/c nude mice, the quantity of metastases nodes was lower in the RASSF5-overexpressed group than that in the control group (P=0.049).

    Conclusion

    ·RASSF5 may inhibit epithelial-mesenchymal transition through GSK-3β/Snail pathway, and then inhibits the invasion and metastasis ability of HNSCC cells.

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    Identification of differentially expressed gene modules in major depressive disorder based on weighted gene co-expression network analysis
    Rui-jie GENG, Lin YAO, Xin-xin HUANG, Shun-ying YU, Cheng-mei YUAN, Wu HONG, Qin-yu LÜ, Qing-zhong WANG, Zheng-hui YI, Yi-ru FANG
    2021, 41 (6):  724-731. 
    doi: 10.3969/j.issn.1674-8115.2021.06.004

    Abstract ( 152 )   HTML ( 11 )   PDF (5613KB) ( 98 )  
    Objective

    ·To explore the differential gene modules and hub genes of major depressive disorder (MDD) by weighted gene co-expression network analysis (WGCNA), and annotate the biological functions of the differential gene modules.

    Methods

    ·Based on the previous experiment of peripheral blood mRNA microarray analysis of 8 MDD patients and 8 healthy controls (control group), t-test statistical method was used to screen the differentially expressed genes between MDD and the control group. WGCNA package in R software was used to analyze the weighted gene co-expression network. The correlation coefficient threshold was set to 0.9 with β =14 to construct the co-expression network of the gene dataset. The hybrid dynamic tree cutting method was used to cut the network to generate gene modules. Pearson correlation test was used to evaluate the correlation between gene modules and MDD. The gene modules with the strongest positive correlation and the strongest negative correlation with depression were selected respectively, and the top three genes with the highest connectivity in the modules were defined as hub genes. Finally, GO functional enrichment analysis and KEGG pathway analysis were used to annotate the functions of the two modules.

    Results

    ·A total of 4 125 differentially expressed genes were obtained from 16 samples, and 9 gene modules were identified. The blue module (R=-0.91, P=0.000) and the cyan module (R=0.76, P=0.000) were selected for further study. The hub genes of blue module were JAM2 (junctional adhesion molecule 2), SCRN2 (secernin 2) and IGHV7-81 (immunoglobulin heavy variable 7-81). The hub genes of cyan module were SCFD2 (Sec1 family domain containing 2), NR5A2 (nuclear receptor subfamily 5 group A member 2) and KCNMA1 (potassium calcium-activated channel subfamily M alpha 1). It was found in the annotation of biological function that the genes of the cyan module were mainly enriched in the embryo development, cell growth and immune and inflammatory response, while the genes of the blue module were mainly enriched in material processing and transport and infection.

    Conclusion

    ·Two peripheral blood mRNA gene modules and six hub genes (JAM2, SCRN2, IGHV7-81, SCFD2, NR5A2 and KCNMA1) may be significantly associated with MDD. These two gene modules may play a role in the embryonic development, immune and inflammatory response, and material processing and transportation.

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    Evaluation of JDBM porous scaffold coated with DCPD in promoting angiogenesis and repairing bone defects
    Qing WANG, Wei WANG, Da-jun JIANG, Wei-tao JIA
    2021, 41 (6):  732-740. 
    doi: 10.3969/j.issn.1674-8115.2021.06.005

    Abstract ( 114 )   HTML ( 16 )   PDF (8449KB) ( 146 )  
    Objective

    ·To evaluate the biological effects of JDBM (Mg-Nd-Zn-Zr) scaffold coated with DCPD (CaHPO4·2H2O) on angiogenesis and repairing bone defects in vivo and in vitro.

    Methods

    ·The JDBM-DCPD and JDBM-MgF2 scaffolds were constructed by using template replication method and chemical deposition method, and the characteristics of the scaffolds were observed by micro-CT and scan electron microscope. The bone marrow mesenchymal stem cells (BMSCs) were seeded on the scaffolds and the biocompatibility of scaffolds was evaluated by CCK-8 experiment and cell adhesion experiment. Transwell cell migration experiment and tube formation experiment were used to detect the effects of scaffold extracts on the migration and tube-forming ability of endothelial cell line Ea.hy926 cells, and immunofluorescence was used to further observe the secretion of vascular endothelial growth factor (VEGF). Alkaline phosphatase staining and alizarin red staining were used to detect the effect of the extracts on the osteogenic ability of BMSCs. Furthermore, the model of critical bone defect of femoral condyle was constructed in SD rats. The JDBM-DCPD and JDBM-MgF2 scaffolds were implanted into the defects, respectively, and the effects of scaffolds on the osteogenesis and vascularization were assessed by Microfil vascular perfusion, micro-CT scanning, and tissue section staining after 8 weeks of operation.

    Results

    ·The main spherical pore size of JDBM-DCPD scaffold was 400?450 μm and the calcium and phosphorus particles were evenly distributed on the pore wall with the size of 15?25 μm. BMSCs adhered and grew well on the surface of JDBM-DCPD scaffold. Compared with the control group and the JDBM-MgF2 scaffold extract, the JDBM-DCPD scaffold extract could significantly promote the migration, tube formation and VEGF expression of Ea.hy926 cells, and significantly enhance the early and late osteogenic differentiation of BMSCs in vitro. After 8 weeks of implantation, the JDBM-DCPD scaffold dramatically facilitated the regeneration of new bone and new vessels in the defect area compared with the JDBM-MgF2 scaffold.

    Conclusion

    ·The JDBM-DCPD scaffold exhibits excellent vascularization effects both in vivo and in vitro, especially early vascularization effect after implantation and bone regeneration promotion in vivo.

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    Exploratory study on downregulation of PD-L1 in KRAS G12V-mutant non-small cell lung cancer cells by selumetinib
    Yun-fang MA, Li-na PAN, Zhen LI, Bei-li GAO, Jia-an HU, Zhi-hong XU
    2021, 41 (6):  741-748. 
    doi: 10.3969/j.issn.1674-8115.2021.06.006

    Abstract ( 155 )   HTML ( 5 )   PDF (3442KB) ( 53 )  
    Objective

    ·To investigate the correlation between Kirsten rat sarcoma viral oncogene(KRAS)-mutant subtypes and programmed cell death ligand 1 (PD-L1) expression in the non-small cell lung cancer (NSCLC) tissues and cell lines, and the possible underlying mechanism.

    Methods

    ·Real-time quantitative PCR and fluorescence-activated cell sorting were used to verify the correlation between PD-L1 mRNA or protein and KRAS mutation status in the NSCLC cell lines. Immunohistochemistry was used to detect the expression of PD-L1 in the tumor tissues of 77 NSCLC patients with early stages (Ⅰa?Ⅱb). The effect of KRAS mutation on the cytokines in the RAS downstream signaling pathway, i.e., protein kinase B (PKB or AKT), mammalian target of rapamycin (mTOR), ribosomal S6 protein kinase (p70S6K), and extracellular regulated protein kinase (ERK), was studied by Western blotting. Dabrafenib (RAF inhibitor), selumetinib [mitogen activated-protein kinase (MEK) inhibitor], GDC0941 (phosphoinositide 3-kinase inhibitor), MK2206 (AKT inhibitor), and rapamycin (mTOR inhibitor) were used to treat 6 KRAS-mutant cell lines, respectively, to detect the regulation of these five tyrosine kinase inhibitors on PD-L1 expression.

    Results

    ·In the NSCLC cell lines, the expressions of PD-L1 mRNA and protein in the KRAS mutant cell lines were significantly higher than those in the KARS wild-type cell lines (P<0.05). KRAS G12V- and G12C-mutant cell lines showed the highest expression of PD-L1 mRNA and protein, respectively. For the NSCLC patients with early stages, the proportions of PD-L1 overexpression in the tumor tissues of the patients with KRAS G12V and G12D mutants were significantly higher than those of the patients with KRAS wild-type. Western blotting showed that in the KRAS-mutated NSCLC cell lines, p70S6K was activated, while ERK, AKT and mTOR were not activated. Moreover, 1 μmol/L GDC0941, 0.5 μmol/L MK2206, and 10 nmol/L rapamycin could not affect the expression of PD-L1 in the 6 KRAS-mutant cell lines. Darafenib (5 nmol/L) up-regulated PD-L1 in only one KRAS G12V-mutant cell line and one L19F-mutant cell line (P<0.05), while selumetinib (0.1 μmol/L ) inhibited the expressions of PD-L1 in three KRAS G12V-mutant cell lines and one L19F-mutant cell line (P<0.05) in a dose-dependent manner.

    Conclusion

    ·The expressions of PD-L1 in the tumor tissues and cell lines of NSCLC with KRAS mutation, especially G12V mutation subtype, were higher than those in the NSCLC tissues and cell lines with KRAS wild-type. Selumetinib can downregulate the expression of PD-L1 in KRAS G12V-mutant NSCLC cells, which suggests that KRAS G12V-mutant NSCLC cells may up-regulate the expression of PD-L1 by upregulating MEK.

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    Screening of key genes and pathways involved in lupus nephritis based on GEO database
    Yin LIU, Tao YANG, Yu-sai XIE, Yu-zhu WANG
    2021, 41 (6):  749-755. 
    doi: 10.3969/j.issn.1674-8115.2021.06.007

    Abstract ( 150 )   HTML ( 9 )   PDF (5461KB) ( 58 )  
    Objective

    ·To identify the differentially expressed genes and pathways involved in lupus nephritis (LN) using bioinformatics analysis.

    Methods

    ·The matrix data of GSE32591 dataset was downloaded from the GEO database, and the limma package of R software was applied to standardize and screen the differentially expressed genes. The volcano map and heatmap of the differentially expressed genes were drawn by ggpubr and pheatmap packages. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of differentially expressed genes were performed using DAVID online database, and bar plot and bubble chart were drawn using R software ggplot package. STRING database and Cytoscape software were used to construct protein interaction networks of differentially expressed genes, and MCODE and cytohubba plug-ins were used to screen out the most significant modules and key genes involved in lupus nephritis. GSE99339 dataset was used to verify the differential expression of hub genes.

    Results

    ·The GSE32591 data set was analyzed through the limma package, and 367 differentially expressed genes were obtained, including 253 up-regulated genes and 114 down-regulated genes. GO analysis and KEGG pathway enrichment analysis showed that differentially expressed genes were significantly enriched in virus defense response, cytoplasmic matrix, influenza A, tuberculosis, EB virus infection, complement pathway, etc. A protein interaction network of differentially expressed genes was constructed by STRING and Cytoscape, and 10 pivotal genes related to LN were identified. The hub genes are significantly differentially expressed in the GSE99339 validation dataset.

    Conclusion

    ·The 367 differentially expressed genes and 10 hub genes are potential biomarkers of LN.

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    Clinical research
    Influence of obsessive beliefs and impulsivity traits on symptom dimensions of obsessive-compulsive disorder patients
    Pu-yu LI, Jia-yue CHENG, Qiu-meng GU, Han-yang RUAN, Yong WANG, Qiang LIU, Yan-ru WU, Zhen WANG
    2021, 41 (6):  756-760. 
    doi: 10.3969/j.issn.1674-8115.2021.06.008

    Abstract ( 155 )   HTML ( 4 )   PDF (1120KB) ( 63 )  
    Objective

    ·To test the effects of obsessive beliefs and impulsivity traits on different subtypes of obsessive-compulsive (OCD).

    Methods

    ·A total of 139 non-medicated OCD patients and 110 matched healthy controls (HCs) were enrolled. The clinical symptoms were evaluated separately using Yale-Brown Obsessive Compulsive Scale (Y-BOCS), Obsessive Beliefs Questionnaire-44 (OBQ-44), Barratt Impulsiveness Scale (BIS-11), and Obsessive Compulsive Inventory-Revised (OCI-R). Multiple linear regression analysis was used to evaluate the influence of obsessive beliefs and impulsive traits on symptom dimensions of obsessive-compulsive disorder.

    Results

    ·The scores of all clinical scales of OCD patients were significantly higher than those of HCs (P<0.05). Obtained by multiple regression, the checking score was affected by responsibility/threat estimate (RT) and motor impulsiveness (MI) (B=0.053, P=0.00; B=-2.000, P=0.011); the ordering score was significantly affected by the perfectionism/certainty (PC) belief (B=0.049, P=0.001); the score of obsessing was affected by the belief in RT (B=0.082, P=0.000); the neutralizing score was affected by both RT belief and cognitive impulsiveness (CI) (B=0.038, P=0.006; B=0.248, P=0.044).

    Conclusion

    ·OCD patients with different obsessive-compulsive beliefs and impulsivity traits will conduct different symptoms.

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    Pharmacodynamics of cisatracurium intravenously infused in infants and young children undergoing living donor liver transplantation
    Wen YIN, Teng WANG, Yu-xi ZHOU, Yan-nan HANG, Da-xiang WEN
    2021, 41 (6):  761-763. 
    doi: 10.3969/j.issn.1674-8115.2021.06.009

    Abstract ( 119 )   HTML ( 4 )   PDF (980KB) ( 24 )  
    Objective

    ·To observe pharmacodynamics of cisatracurium intravenously infused in infants and young children with end-stage liver disease during living donor liver transplantation.

    Methods

    ·Sixteen patients of American Society of Anesthesiologists (ASA) physical status Ⅲ and Ⅳ, aged 6-24 months, with end-stage liver disease, undergoing liver transplantation were studied. Neuromuscular transmission was monitored by the responses of the adductor pollicis to train-of-four (TOF) stimulation of ulnar nerve, using the accelerography (TOF-Watch). Endotracheal intubation was performed after intravenous injection of 0.15 mg/kg cisatracurium, with T1 being the maximum inhibitory degree. After recovery of T1 to 3%, cisatracurium was infused at an initial rate of 2 μg/(kg·min). The infusion rate was adjusted to maintain a constant 90% to 95% neuromuscular paralysis until the end of the operation. The onset time, no reaction period of TOF, the dosage of cisatracurium given during paleo-phepatic phase, an-hepatic phase and neo-hepatic phase, the time to 25% recovery of T1, recovery index (25%?75%), and the time for the TOF ratio (TOFr) to reach 0.9 were recorded respectively.

    Results

    ·The infusion rate was (1.37±0.46) μg/(kg·min). The average infusion rate of drugs in the three different periods showed a downward trend, but there was no statistical difference (P=0.110). The onset time of cisatracurium was (242.63±46.74) s. The no reaction period of TOF was (34.02±7.71) min. Following termination of the infusion, the time to 25% recovery of T1 was (12.80±3.49) min, and the recovery index (25%?75%) was (15.12±4.59) min. The time of TOFr=0.9 was (40.27±7.03) min.

    Conclusion

    ·The pharmacodynamical characteristics of muscle relaxants should be fully understood during living donor liver transplantation in infants and young children with end-liver disease. When cisatracurium (0.15 mg/kg) is used for anesthesia induction, endotracheal intubation should be performed 4 min after administration. In the maintenance stage of anesthesia, the infusion dose requirement of cisatracurium is basically unchanged in the three different periods,and the infusion rate of 1.4 μg/(kg·min) can provide satisfactory muscle relaxation effect.

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    A clinical study on treatment failure of childhood acute lymphoblastic leukemia
    Jia-shi ZHU, Hong LI, Jing-bo SHAO, Na ZHANG, Jing-wei YANG, Kai CHEN, Zhen WANG, Hui JIANG
    2021, 41 (6):  764-769. 
    doi: 10.3969/j.issn.1674-8115.2021.06.010

    Abstract ( 154 )   HTML ( 5 )   PDF (1386KB) ( 62 )  
    Objective

    ·To analyze the reasons for the treatment failure of childhood acute lymphoblastic leukemia (ALL), and explore the strategy in failure reduction.

    Methods

    ·A retrospective study was conducted on the cases with treatment failure in 330 children who were initially diagnosed as having ALL in Shanghai Children's Hospital from January 2006 to June 2017 to analyze the reasons for failure. The clinical characteristics of the children with different reasons were analyzed respectively. Kaplan-Meier survival curve analysis and COX regression model were used to explore the recurrence rate, overall survival (OS) rate and risk factors of recurrence. The difference of the stages of infection occurrence in the children with different risk levels was explored by χ2 test.

    Results

    ·Among the 330 children with ALL, 84 cases failed in treatment. The reasons for treatment failure included disease recurrence (58 cases), death due to severe infection (19 cases), second tumor occurrence (2 cases), and death from other causes (5 cases). Totally 58 ALL children relapsed, whose median recurrence time was 27 (2-95) months. The 5-year cumulative recurrence rate was (18.2 ± 2.3)%, and the 10-year cumulative recurrence rate was (22.4 ± 2.9)%. Multivariate analysis showed that poor treatment response in the early stage (HR=5.43, P=0.000) and medium and high risk of disease (HR=2.26, P=0.017) were independent risk factors for recurrence. According to the recurrence time, the 5-year OS rate of children with very early recurrence was (16.7±10.2)%, significantly lower than that of children with early and late recurrence (P=0.000). According to the location of recurrence, the 5-year OS rate of children with simple bone marrow recurrence was (42.0±10.2)%, significantly lower than that of children with simple extramedullary recurrence (P=0.044). Of the 55 children with severe infection, 26 cases had sepsis, 20 cases had respiratory infection with acute respiratory distress syndrome, and 9 cases had severe intestinal infection. There were statistically significant differences in the stage distribution of infection occurrence in the children with different risk levels (P=0.019). Low-risk children were more likely to have serious infection during the induction and consolidation treatment phase (P=0.022), and medium-and-high-risk children were more likely to have serious infection in the mid-stage of intensive treatment (P=0.044).

    Conclusion

    ·Recurrence and death from infection are the main causes for treatment failure in childhood ALL. Active prevention and treatment of very early recurrence and infection can reduce the incidence of treatment failure and improve the long-term survival rate of the children.

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    Value of blood lipoprotein phospholipase A2 and neutrophil gelatinase-associated lipocalin in the diagnosis of early diabetic nephropathy
    Jia-si ZHANG, Chun-bo ZOU, Yu LU, Xi CHEN, Wei-ya ZHANG, Jiao-jiao HE
    2021, 41 (6):  770-775. 
    doi: 10.3969/j.issn.1674-8115.2021.06.011

    Abstract ( 119 )   HTML ( 5 )   PDF (1274KB) ( 58 )  
    Objective

    ·To examine the role of blood lipoprotein phospholipase A2 (Lp-PLA2) and neutrophil gelatinase-associated lipocalin (NGAL) in the diagnosis of early diabetic nephropathy (DN).

    Methods

    ·A total of 219 participants with type 2 diabetes mellitus diagnosed in the Department of Endocrinology of Taizhou People's Hospital from January 2017 to April 2019 were enrolled. The levels of Lp-PLA2, NGAL, urinary albumin excretion rate (UAER), blood urea nitrogen (BUN), serum creatinine (Scr), uric acid (UA), cystatin C (Cys-C), blood glucose, and blood lipid in all participants were detected. All diabetics were classified into three groups based on UAER: normal albuminuria (NA) group (n=75), microalbuminuria (MA) group (n=73) and heavy albuminuria (HA) group (n=71). The MA group and HA group were classified as DN group.The differences of the above indicators among each group were compared, and the relationship of Lp-PLA2, NGAL and DN were analyzed by Pearson linear correlation, multiple linear regression, Logistic regression and receiver operator characteristic curve.

    Results

    ·Compared with the NA group and MA group, the levels of Lp-PLA2, NGAL, BUN, SCr, UA and Cys-C in the HA group were significantly increased (P<0.05). However, compared with the NA group, only Lp-PLA2 and NGAL levels in the MA group were significantly increased (P<0.05). Correlation analysis found the Lp-PLA2 and NGAL were positively correlated with UAER (r=0.397, r=0.511), BUN (r=0.274, r=0.411), SCr (r=0.237, r=0.419), and Cys-C (r=0.278, r=0.436) (all P=0.000), whereas negatively correlated with the estimate glomerular filtration rate (r=-0.170, r=-0.366; P=0.013, P=0.000). Multiple linear regression analysis showed that Lp-PLA2, NGAL and Cys-C were related factors of UAER. Binary Logistic regression analysis found that Lp-PLA2 and NGAL were still risk factors of kidney injury in DN after adjustment for blood pressure, lipids, glycosylated hemoglobin and duration of diabetes (OR=1.012, OR=1.024; P=0.009, P=0.000). The area under the curve (AUC) of Lp-PLA2, NGAL and their combination in diagnosis of DN were 0.700, 0.855 and 0.871. NGAL demonstrated high sensitivity (81.2%) and specificity (80.0%). Lp-PLA2- and NGAL-combined detection had the highest diagnostic efficiency (AUC=0.871).

    Conclusion

    ·Both blood Lp-PLA2 and NGAL levels are closely associated with the renal damage in participants with DN. As independent risk factors of DN, Lp-PLA2 and NGAL have been highly expressed in early DN, which could better reflect the occurrence of early DN, compared with traditional renal function indicators. Lp-PLA2- and NGAL-combined detection could demonstrate its maximum diagnostic efficacy, providing a new method for the diagnosis of early renal injury.

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    Observation of therapeutic efficacy of metformin on glucose dysregulation and dyslipidaemia induced by quetiapine in patients with schizophrenia
    Bing-fu SONG, Bin-bin Ding, Xiao-li ZHANG, Li-yun YAO
    2021, 41 (6):  776-780. 
    doi: 10.3969/j.issn.1674-8115.2021.06.012

    Abstract ( 161 )   HTML ( 7 )   PDF (1347KB) ( 62 )  
    Objective

    ·To investigate the therapeutic efficacy of metformin (MF) on glucose dysregulation and dyslipidaemia induced by quetiapine in patients with schizophrenia (SZ).

    Methods

    ·A total of 83 SZ patients from Shanghai Hongkou District Mental Health Center and Shanghai Yangpu District Mental Health Center were enrolled, and randomly divided into treatment group (MF group, n=38) and control group (n=45). The control group received oral quetiapine therapy, and the MF group additionally received metformin on the basis of oral quetiapine therapy. The serum levels of glucose (GLU), total cholesterol (TC), triacylglycerol (TAG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), small density low-density lipoprotein cholesterol (sd-LDL-C) and homocysteine (HCY) were determined before treatment and 2, 4 and 8 weeks after treatment.

    Results

    ·There were no statistic differences in ages, courses, body mass index, the levels of GLU, TC, TAG, HDL-C, LDL-C, sd-LDL-C and HCY between the control and MF group before treatment (all P>0.05). After 8 weeks of treatment, levels of all biomarkers elevated in the control group. The levels of GLU, TC, TAG, LDL-C, sd-LDL-C and HCY were lower after treatment, and the level of HDL-C elevated higher in the MF group. The variations of levels of HDL-C after treatment showed statistically no significant difference between the two groups (P=0.247), while statistical differences existed in other biomarkers, which indicated that the glucose-lowering and lipid-lowering efficacies in the MF group were significantly better than those in the control group. The analysis of variance suggested that, in the control group, the level of HDL-C elevated significantly after 4 and 8 weeks′ treatment, having statistical differences (P=0.005 and P=0.003). The level of LDL-C elevated significantly after 2, 4 and 8 weeks′ treatment (P=0.005, P=0.019 and P=0.026), and no statistical differences were observed in other biomarkers. In the MF group, the levels of GLU, TC, TAG and sd-LDL-C were lower 2, 4 and 8 weeks after treatment, the levels of LDL-C and HCY descended 4 and 8 weeks after treatment, and no statistical differences were observed in other biomarkers. The level of HDL-C was higher after 2 weeks, treatment, but showed statistically no significant differences 4 and 8 weeks after treatment, compared to the level determined before treatment.

    Conclusion

    ·Administration of MF in the SZ patients having glucose dysregulation and dyslipidaemia induced by quetiapine can significantly lower serum level of GLU, and improve the serum lipid profiles.

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    Effect of positive end-expiratory pressure on the incidence of atelectasis in children with congenital heart disease undergoing lateral thoracotomy under cardiopulmonary bypass
    Pan HE, Ying SUN, Yan-yan YANG, Jie BAI, Ji-jian ZHENG, Ma-zhong ZHANG
    2021, 41 (6):  781-785. 
    doi: 10.3969/j.issn.1674-8115.2021.06.013

    Abstract ( 154 )   HTML ( 4 )   PDF (1537KB) ( 40 )  
    Objective

    ·To evaluate the incidence of atelectasis in children undergoing lateral thoracotomy cardiac surgery with cardiopulmonary bypass (CPB) by lung ultrasound, and investigate the effect of positive end-expiratory pressure (PEEP) on the incidence of atelectasis in these children.

    Methods

    ·Sixty children undergoing selective lateral thoracotomy cardiac surgery with CPB in Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine from October 2019 to August 2020 were included. They were randomly divided into PEEP group (P group, n=30) and control group (C group, n=30). The P group was treated with 5 cmH2O PEEP immediately after tracheal intubation until the end of operation. The C group was treated with 5 cmH2O PEEP immediately after tracheal intubation until the beginning of operation. Lung ultrasound exam was performed three times in each patient, 1 min after starting mechanical ventilation of the lungs (T1), 1 min before the beginning of surgery (T2) and the time immediately upon completion of the surgery (T3). The lung ultrasound scores of the two groups were recorded, and the incidences of atelectasis were compared.

    Results

    ·There was no significant difference in the incidences of atelectasis at T1 and T2 between the two groups. The incidence of atelectasis in P group was significantly lower than that in the C group at T3 (P=0.000). The incidence of atelectasis in the C group at T3 was significantly lower than those at T1 and T2 (all P<0.05).

    Conclusion

    ·PEEP can significantly reduce the incidence of atelectasis in children undergoing lateral thoracotomy cardiac surgery with CPB.

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    Evidence-based medicine
    Meta-analysis of the effect of BRAF gene mutation on the prognosis of colorectal cancer patients with liver metastases after hepatectomy
    Sheng CHENG, Yi ZHAO, Yong-chen WANG, Ping HUANG
    2021, 41 (6):  786-792. 
    doi: 10.3969/j.issn.1674-8115.2021.06.014

    Abstract ( 115 )   HTML ( 5 )   PDF (1898KB) ( 33 )  
    Objective

    ·To assess the impact of BRAF gene mutation on the prognosis of colorectal cancer liver metastasis (CRLM) patients after hepatectomy.

    Methods

    ·The clinical research was obtained from PubMed from January 2010 to June 2020. Retrieval method was as follows: "BRAF" and ("colon" or "colorectal" or "rectal" or "rectum") and ("metastasis" or "metastatic" or "metastases" or "mets" or "metastasectomy") and ("hepatic" or "liver"). The articles were screened according to inclusion and exclusion criterias, and the quality evaluation and data extraction were carried out. The RevMan 5.4 software was used for meta-analysis. The main outcome index was overall survival (OS), and the secondary outcome index was disease-free survival (DFS).

    Results

    ·Finally, seven studies containing 2 722 patients were included in the meta-analysis. The mutation rate of BRAF was 5.77%. Seven studies reported CRLM patients' OS after hepatic resection through stratified analysis by BRAF gene status. The result of meta-analysis showed that hazard ratio (HR)=3.04, 95% CI 2.30-4.01, P=0.000. That was statistically significant. It indicated that the OS of CRLM patients with BRAF mutation was shortened after hepatectomy. HR funnel plot of OS was basically symmetrical, and no obvious publication bias was found. Three studies reported 1 237 CRLM patients'DFS after hepatectomy through stratified analysis by BRAF gene status. The mutation rate of BRAF was 9.62%. The result of meta-analysis showed that HR=2.07, 95%CI (1.06-4.03), P=0.03. That was statistically significant. It indicated that the DFS of CRLM patients with BRAF mutation was shortened after hepatectomy. HR funnel plot of DFS was asymmetric, and it was uncertain whether there was publication bias, which may be related to the small sample size included in the study.

    Conclusion

    ·BRAF mutation is a biomarker of poor prognosis in CRLM patients after hepatectomy. It is related to poor OS, and more studies are needed to confirm the relationship with poor DFS.

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    Public health
    Validity and reliability of the Chinese version of Defeat Scale in men who have sex with men
    Shang-bin LIU, Hao YANG, Chen XU, Jing-wen DONG, Xiao-yue YU, Yong CAI, Dong YUAN, Ying WANG
    2021, 41 (6):  793-798. 
    doi: 10.3969/j.issn.1674-8115.2021.06.015

    Abstract ( 159 )   HTML ( 3 )   PDF (1456KB) ( 36 )  
    Objective

    ·To test the reliability and validity of the Chinese version of Defeat Scale (DS) in the men who have sex with men (MSM) in Shanghai and Shenyang, China, and explore its value in judging the depressive state of the population.

    Methods

    ·A cross-sectional survey was conducted among 530 men over the age of 18 who had made sex with men in the past 6 months in Shanghai and Shenyang. DS and Patient Health Questionnaire-9 (PHQ-9) were used. Excel 2010 was used to establish the database, and SPSS 23.0 and Amos 25.0 software were used to analyze the reliability and validity of the data. Shapiro-Wilk test was used to determine whether the data obeyed normal distribution. Exploratory factor analysis and confirmatory factor analysis were used to verify its structural validity of DS. Spearman correlation coefficient was conducted to evaluate the content validity. Cronbach's α coefficient and Spearman-Brown coefficient were used to evaluate the reliability of DS. Binary Logistic regression was used to determine whether defeat can affect depression, and then, receiver operator characteristic (ROC) curve was used to determine its diagnostic value.

    Results

    ·The data of DS and PHQ-9 did not obey the normal distribution. The exploratory factor analysis showed that two factors including decadence (13 items) and low sense of achievement (3 items) could be extracted. Explained variance of the scale was 69.35%. The confirmatory factor analysis showed that each item of the revised two-factor model was greater than 0.50, and the minimum value was 0.52. The model fitted well [ χ2/df =3.430<5; root mean square error of approximation (RMSEA)= 0.068, standardized root mean square residual (SRMR)=0.043, all<0.080; normed fit index (NFI)=0.944, incremental fit index (IFI)=0.959, comparative fit index (CFI)=0.959, goodness of fit index (GFI)=0.909, Tucker-Lewis Index (TLI)=0.958, all>0.900]. The Cronbach's α coefficient of DS of the 16 items was 0.934, and the Cronbach's α of two dimensions, namely "decadence" and "low achievement" were 0.962 and 0.758, respectively. With depression as the dependent variable and DS score as the covariant, binary Logistic regression was carried out. The results showed that β value was 0.178, P=0.000. Odds ratio (OR) value was 1.195 and 95% confidence interval (CI) was 1.147-1.245. The area under the curve (AUC) was 0.891, P=0.000. The maximum Youden index value was 0.667, its corresponding DS score was 21.5, and its sensitivity and specificity were 87.0% and 80.7%, respectively.

    Conclusion

    ·The Chinese version of DS has good reliability and validity in MSM, and also has the value in judging the state of depression in this population.

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    Review
    Cardiovascular involvement in propionic acidemia and related mechanisms
    Ying LIU, Yu-rong WU, Kun SUN
    2021, 41 (6):  799-802. 
    doi: 10.3969/j.issn.1674-8115.2021.06.016

    Abstract ( 116 )   HTML ( 4 )   PDF (991KB) ( 27 )  

    Propionic acidemia (PA) is an autosomal recessive disorder of organic acidemia. In addition to developmental delay and central nervous system damage, its most important mid- and long-term complications include dilated cardiomyopathy and arrhythmia (long Q-T syndrome and ventricular fibrillation, etc.), which are also major causes of mortality. The mechanisms of cardiovascular involvement include disorder of mitochondrial energy metabolism, oxidative stress and ion channel damage caused by excessive metabolites such as propionic acid. There are no recognized guidelines for the treatment of PA-related cardiomyopathy. Liver transplantation is recognized as a method to correct metabolic disorders and reverse cardiomyopathy. Antioxidants and drugs that increase myocardial energy supply are expected to become the future treatment options for PA-related cardiomyopathy.

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    Research progress in health risk assessment of perfluorinated compounds among Chinese population
    Qian YAO, Ying TIAN
    2021, 41 (6):  803-808. 
    doi: 10.3969/j.issn.1674-8115.2021.06.017

    Abstract ( 139 )   HTML ( 14 )   PDF (1159KB) ( 100 )  

    Perfluorinated compounds (PFAS) are a new class of persistent organic pollutants that have attracted wide attention in recent years. With the increasing restrictions on PFAS in Europe and the United States, the production of PFAS is gradually transferring to China. The amount of PFAS used in China is increasing year by year, but there are no strict restrictions on the use of them. Furthermore, the safety limits are heading down in Europe and the United States. Based on the updated safety limits, studies in Chinese population have gradually indicated the potential risk of PFAS. This review summarizes the updated international safety limits, and introduces the research progress in health risk assessment of PFAS exposure in Chinese population according to different sources of exposure (diet, milk, drinking water, dust, atmosphere, placental transfer and comprehensive sources). The existing studies mainly focus on the health risk of PFAS exposure in high PFAS-polluted areas and in sensitive infant population in China, while the health risk of PFAS exposure in general population still needs to be further evaluated. It is necessary to carry out relevant work, which can provide reference for relevant government departments to formulate PFAS control standards and safety limits in line with China's national conditions as soon as possible. In addition, the future assessment research should pay more attention to complex evaluation of various sources of PFAS and the health hazards of PFAS alternatives.

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    Research progress of RNA m6A methylation modification in regulating tumor function and its inhibitors
    Ya-juan HAO, Ying-bin LIU
    2021, 41 (6):  809-814. 
    doi: 10.3969/j.issn.1674-8115.2021.06.018

    Abstract ( 116 )   HTML ( 292 )   PDF (1214KB) ( 57 )  

    RNA modifications play an important role in physiology and pathology. N6-methyladenine (m6A) has been identified as a prevalent methylation modification on eukaryotic RNAs. RNA m6A can be reversible. In recent years, abnormal expression of the RNA m6A modification enzymes and binding proteins have been found in tumors, and they promote or inhibit the tumor progression by altering the mRNA m6A modification levels of the target genes. This paper reviews the important functions of FTO α-ketoglutarate dependent dioxygenase, AlkB homolog 5 (ALKBH5) and methyltransferase like 3 (METTL3) in a variety of tumors, and also reports their small molecule inhibitors.

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    Recent progresses in deep brain stimulation of subthalamic nucleus on Parkinson′s disease and its related depression
    Xiao-xiao ZHANG, Chen-cheng ZHANG, Yi-jie LAI, Bo-min SUN
    2021, 41 (6):  815-820. 
    doi: 10.3969/j.issn.1674-8115.2021.06.019

    Abstract ( 114 )   HTML ( 5 )   PDF (1148KB) ( 38 )  

    Depression is a common non-motor symptom of Parkinson′s disease (PD) and is a critical factor in the reduction of life quality of PD patients. The therapeutic effect of subthalamic nucleus deep brain stimulation (STN-DBS) on PD motor symptoms has been well documented. However, their effect on the related depression in PD is inconclusive. This article reviews the epidemiological characteristics and pathogenesis of PD and its related depression, the mechanism underlying the effects of STN-DBS on PD-related depression, the imaging and electrophysiological research of STN-DBS on PD and its related depression, the effects of STN-DBS on drug use, and the effects of electrode position on emotion.

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    Advances in diagnostic methods of clinical staging for gastric cancer
    Jiang-lei MA, Xiao-yao LI, Shi-fu ZHAO, De-jun YANG
    2021, 41 (6):  821-825. 
    doi: 10.3969/j.issn.1674-8115.2021.06.020

    Abstract ( 111 )   PDF (1140KB) ( 38 )  

    Accurate clinical staging of gastric cancer is of great significance for choosing an optimal therapeutic schedule and evaluating the prognosis. In recent years,objective evidences have been provided owing to the use of diagnostic methods such as gastroscopy, endoscopic ultrasound, multi-detector row computed tomography, magnetic resonance imaging and positron emission tomography-computed tomography, which have greatly enhanced the accuracy of clinical staging diagnosis for gastric cancer. This paper reviews the research progress in current clinical examining techniques for clinical staging diagnosis.

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    Research progress in myocardial ischemia-reperfusion injury mediated by mitochondrial reactive oxygen species
    Ya-zhong WEI, Xiao-mei XUE, Bin HE
    2021, 41 (6):  826-829. 
    doi: 10.3969/j.issn.1674-8115.2021.06.021

    Abstract ( 135 )   HTML ( 4 )   PDF (932KB) ( 39 )  

    With the development of percutaneous coronary intervention technology, acute myocardial infarction has been effectively treated, but the myocardial ischemia-reperfusion injury (MIRI) has seriously affected the prognosis of patients. During the ischemia-reperfusion period of acute myocardial infarction, oxidative stress can seriously damage cardiac function. Excessive mitochondrial reactive oxygen species (mtROS) can affect mitochondrial permeability, and cause oxidative damage of specific molecules inside the mitochondria, which is the main driving factor for MIRI. In addition, mtROS can promote the signal transduction of inflammatory after myocardial infarction, regulate myocardial cell apoptosis, and participate in myocardial remodeling after myocardial infarction. This article reviews the mechanism of mtROS production in MIRI period and the clinical value and application prospect of reducing mtROS in the treatment of myocardial infarction.

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    Expression and significance of ATP-binding cassette superfamily G member 2 in lung cancer
    Jian-hua XU, Ping JIANG, Jiong DENG
    2021, 41 (6):  830-833. 
    doi: 10.3969/j.issn.1674-8115.2021.06.022

    Abstract ( 125 )   HTML ( 1 )   PDF (964KB) ( 42 )  

    The stemness and drug resistance of lung cancer cells are important features of malignancy. ATP-binding cassette superfamily G member 2 (ABCG2), a member of the ATP-binding cassette transporter family, is localized in the membrane of a variety of human cancer cells and excludes drugs from cells in an ATP-dependent manner. Single nucleotide polymorphisms in ABCG2 gene are significantly associated with multidrug resistance in cancer chemotherapy. In addition, ABCG2 has been used as a supporting biomarker for the identification of lung cancer stem cells. This review summarizes recent research progress in ABCG2, focusing on the regulation of ABCG2 gene expression, the potential roles of ABCG2 on cancer cell stemness, and the correlation of single nucleotide polymorphisms in ABCG2 with drug resistance in lung cancer, in order to provide a new strategy for the clinical treatment of lung cancer patients.

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    Advances in the role of growth differentiation factor 11 in cardiovascular diseases
    Ming-qi CAI, Yan CHEN, Kai-bin LIN, Dong HUANG
    2021, 41 (6):  834-838. 
    doi: 10.3969/j.issn.1674-8115.2021.06.023

    Abstract ( 144 )   HTML ( 4 )   PDF (1094KB) ( 59 )  

    Growth differentiation factor 11 (GDF11) is an important member of transforming growth factor-β (TGF-β) superfamily. As a secreted protein widely distributed in human body, it is associated with many physiological activities, including early embryonic and bone development, neural regulation, and maturation of tissues and organs such as retina and kidney. Recent studies have shown that GDF11 is closely related to aging and cardiovascular diseases, but its specific effects and mechanism are controversial. Some studies have drawn the conclusions that increased levels of GDF11 can reduce myocardial hypertrophy, alleviate inflammatory damage and protect the function of vascular endothelial cells. Meanwhile, some studies have reached the opposite conclusions. So the issue that whether GDF11 has a protective effect on cardiovascular diseases remains uncertain. This article reviews the research progress and essential divergence of GDF11 in the field of cardiovascular diseases, in order to provide reference for future investigation.

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