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    Electron microscopic study of the human MDN1 protein
    Yun-tao XU, Ming-yue LI, Ming LEI
    2021, 41 (5):  559-564. 
    doi: 10.3969/j.issn.1674-8115.2021.05.001

    Abstract ( 452 )   HTML ( 28 )   PDF (3400KB) ( 208 )  
    Objective

    ·To study the structure of the human midasin AAA-ATPase 1 (MDN1, Rea1) protein by negative-staining electron microscopy.

    Methods

    ·Using the CRISPR/Cas9 genome editing method, a 3×FLAG affinity tag was inserted into the N-terminus of MDN1 in Expi293F cells. Tagged proteins were isolated via affinity purification with ANTI-FLAG? M2 Agarose Affinity Gel, followed by glycerol density gradient centrifugation. The purified protein sample was then subjected to negative-staining electron microscopy and single particle image analysis.

    Results

    ·The FLAG-tagged endogenous MDN1 proteins with high purity and good homogeneity were obtained using affinity chromatography and density gradient centrifugation. Preliminary study on the structure of human MDN1 was achieved by 120 kV electron microscope after negative staining with uranium formate.

    Conclusion

    ·A low resolution model of human MDN1 protein was achieved by single particle reconstruction analysis.

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    Basic research
    Establishment of a novel mice model of heart failure with preserved ejection fraction
    Xiao-nan CHEN, Jun-feng ZHANG, Chang-qian WANG, Hui-li ZHANG
    2021, 41 (5):  565-570. 
    doi: 10.3969/j.issn.1674-8115.2021.05.002

    Abstract ( 416 )   HTML ( 25 )   PDF (2075KB) ( 185 )  
    Objective

    ·To establish a novel mice model of heart failure with preserved ejection fraction (HFpEF).

    Methods

    ·Sixteen 8-week-old SPF grade male and female C57BL/6J mice each were randomly divided into control group or model group (n=8 per group). The model group was given high-fat diet containing 60% fat and drinking water containing 0.5 g/L Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME). The control group was given routine feed and drinking water. The ratio of peak early mitral velocity to peak late mitral velocity (E/A ratio) and the ratio of peak early mitral velocity to peak early diastolic mitral annular velocity (E/E' ratio) were detected by echocardiography every two weeks to evaluate left ventricular diastolic function. At the 16th week after modeling, the myocardial hypertrophy and fibrosis were examined by Masson staining and hematoxylin-eosin staining. The levels of serum triacylglycerol (TAG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-Ch) and low-density lipoprotein cholesterol (LDL-Ch) were detected by automatic biochemical analyzer.

    Results

    ·HFpEF appeared in the male mice at 8 weeks after high-fat diet and L-NAME administration, with a significant increase in E/A ratio and E/E′ ratio in comparison to the male control group (both P=0.000). There was no significant difference in the left ventricular ejection fraction (LVEF) between male model group and male control group. On the other hand, the female mice fed with high-fat diet and drinking water containing L-NAME also displayed obvious HFpEF after 8 weeks. E/A ratio and E/E' ratio in female model group were significantly higher than those in the female control group (P=0.000, P=0.001). There was no significant difference in LVEF between female model group and female control group. At the 16th week after modeling, both male and female mice still displayed the characteristics of HFpEF. Systolic blood pressure and diastolic blood pressure of male and female model group were significantly higher than those of respective control groups. Male or female mice with HFpEF showed obvious myocardial hypertrophy and fibrosis along with left ventricular remodeling. The serum levels of TAG, TC, HDL-Ch and LDL-Ch in the model groups were significantly higher than those in the respective control groups.

    Conclusion

    ·High-fat feeding combined with L-NAME administration can induce HFpEF in both male and female mice.

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    Identification of core genes in pancreatic cancer progression by bioinformatics analysis
    Lu-di YANG, Gao-ming WANG, Ren-hao HU, Xiao-hua JIANG, Ran CUI
    2021, 41 (5):  571-578. 
    doi: 10.3969/j.issn.1674-8115.2021.05.003

    Abstract ( 404 )   HTML ( 26 )   PDF (5114KB) ( 118 )  
    Objective

    ·To select pancreatic cancer progression-related core genes and key pathways.

    Methods

    ·The dataset GSE28735 for pancreatic cancer was obtained by searching and screening in the Gene Expression Omnibus (GEO) database. Genes in 45 cases of cancer tissues and 45 cases of normal tissues adjacent to cancer were extracted by GEO2R and combined with RStudio to screen and visualize differentially expressed genes (DEGs). Genes with significant differential expression were analyzed by gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis through the gene utilization function annotation online tool DAVID. The protein-protein interaction (PPI) network was constructed by using the interactive gene retrieval tool, STRING and Cytoscape, to further screen core genes based on the node degree value. The relationship between the expression levels of core genes and overall survival (OS), disease-free survival (DFS) and tumor stage of 179 cases of patients was analyzed through the gene expression profile analysis database GEPIA.

    Results

    ·A total of 131 DEGs were screened from the dataset GSE28735, including 115 up-regulated genes and 16 down-regulated genes. GO function enrichment analysis showed that DEGs were mainly enriched in cell adhesion, plasma membrane, and protein binding. KEGG pathway enrichment suggested that phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) was the main signaling pathway for DEG enrichment. Five core genes, fibronectin1 (FN1), mesenchymal to epithelial transition factor (MET), polyclonal antibody to laminin β3 (LAMB3), laminin subunit α3 (LAMA3), and integrin subunit α3 (ITGA3),were obtained through PPI network screening. The expression levels of MET, LAMA3, LAMB3 and ITGA3 were associated with OS of patients, and the expression levels of MET, LAMB3 and ITGA3 were associated with DFS. The prognosis of low gene expression group was significantly better than that of high gene expression group. There were significant differences in the expression levels of FN1, MET, LAMA3 and LAMB3 in the different stages of pancreatic cancer.

    Conclusion

    ·The abnormal expression of FN1, MET, LAMB3, LAMA3 and ITGA3 is related to the changes of cell adhesion, plasma membrane component, protein binding function and PI3K/Akt pathway. The increased expression of MET and LAMB3 may predict poor prognosis of patients with pancreatic cancer.

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    Analysis of tumor immune-related differentially expressed genes in adults and children with acute myeloid leukemia
    Ling-ling LI, Qian LI, Ming-yu LI, Zheng LIU, Qian-cheng SHEN
    2021, 41 (5):  579-587. 
    doi: 10.3969/j.issn.1674-8115.2021.05.004

    Abstract ( 265 )   HTML ( 20 )   PDF (5920KB) ( 81 )  
    Objective

    ·To analyze tumor immune-related differentially expressed genes (DEGs) in the bone marrow of adults and children with acute myeloid leukemia (AML).

    Methods

    ·The GSE134589 data set was downloaded from the GEO (Gene Expression Omnibus) database, and the patients in initial diagnosis/relapse were selected and divided into children group (0?16 years old, 34 cases), young and middle-aged group (17?59 years old, 62 cases) and elders group (60?80 years old, 62 cases). The tumor immune-related DEGs in the bone marrow samples of different groups of patients were screened by R language packages. The common DEGs of young and middle-aged group vs children group and elders group vs children group were compared with the DEGs of adults group vs children group in complete remission, and the functional enrichment analysis was conducted with the common DEGs. The Kaplan-Meier method was used to screen the DEGs that were significantly related to prognosis, and the core regulatory DEGs were screened by constructing a protein-protein interaction (PPI) network. The genes screened by the above two methods were regarded as key genes. The expression levels of the key genes in AML, diffuse large B cell lymphoma (DLBCL) and thymoma tumor samples and normal human samples were compared by GEPIA server, and the mRNA expression levels of key genes in the human AML tumor stem cells and the original hematopoietic cells of healthy people were analyzed by GEXC website.

    Results

    ·In the GSE134589 data set, there were 51 DEGs up-regulated and 21 down-regulated between the young and middle-aged group and the children group; 47 DEGs were up-regulated and 20 down-regulated between the elders group and the children group; no DEG was found between the young and middle-aged group and the elders group. Fifty-seven tumor immune-related DEGs were screened in both the young and middle-aged group and the elders group, of which 39 were up-regulated and 18 were down-regulated; in these DEGs only 3 genes showed statistically significant difference in expression level when the disease was incomplete remission. The 57 common DEGs were mainly enriched in leukocyte migration and cytokine-related signal pathways. The patients with high expression of interleukin-2 receptor subunit alpha (IL2RA) and FMS-like tyrosine kinase 3 (FLT3) had significantly shorter overall survival than those with low expression (both P<0.05), and complement component 3a receptor 1 (C3AR1) was the core regulatory gene of the PPI network. The three DEGs were selected as key genes. They were all specifically highly expressed in the AML tumor samples (all P<0.05), and IL2RA was also significantly highly expressed in the DLBCL samples (P<0.05). The expression level of IL2RA was low both in the AML tumor stem cells and the original group of hematopoietic cells, but FLT3 was highly expressed in these cells. The expression level of C3AR1 was specifically high in the AML tumor stem cells.

    Conclusion

    ·The difference in the prognosis between adults and children with AML may be related to the differences in the expression of tumor immune-related genes in bone marrow, in which IL2RA, FLT3 and C3AR1 may be the key genes.

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    Role and clinical significance of intercellular adhesion molecule-1 in CD4+ T cells assisting B cells to produce antibodies
    Qian ZHAO, Mei-yu ZHANG, Ping JI, Jia-yuan WANG, Shu-jun WANG, Shuai LIU, Ying WANG
    2021, 41 (5):  588-594. 
    doi: 10.3969/j.issn.1674-8115.2021.05.005

    Abstract ( 251 )   HTML ( 11 )   PDF (2795KB) ( 165 )  
    Objective

    ·To investigate the role of intercellular adhesion molecule-1 (ICAM-1) in CD4+ T cells assisting B cells to produce antibodies, and the correlation between ICAM-1 and systemic lupus erythematosus (SLE).

    Methods

    ·①From October 2018 to May 2020, 50 SLE patients (SLE group) of Rheumatology Department and 60 healthy people (HC group) of medical examination center from Renji Hospital, Shanghai Jiao Tong University School of Medicine were recruited. Flow cytometry was used to analyze the expression of ICAM-1 on the surface of CD4+ T cells in peripheral blood of the two groups. Enzyme-linked immunosorbent assay (ELISA) was used to detect the soluble ICAM-1 (sICAM-1) level in serum of the two groups. ②Peripheral blood mononuclear cells (PBMCs) of healthy people were isolated by density gradient centrifugation, and activated by α-CD3/28 in vitro at 24, 48 and 72 h, respectively. The expression of ICAM-1 on the surface of CD4+ T cells was analyzed by flow cytometry, and the level of sICAM-1 in the supernatant was detected by ELISA. ③CD4+ T cells and B cells of healthy people were co-cultured in vitro, which were divided into control group, stimulation group and antibody blockade group. After 12 days, the IgG level in the co-culture supernatant of the three groups was detected by ELISA.

    Results

    ·①The expression of ICAM-1 on the surface of CD4+ T cells in peripheral blood and the level of sICAM-1 in serum of the SLE group was higher than that of the HC group (both P<0.05). Correlation analysis showed that ICAM-1 expression on the surface of CD4+ T cells was positively correlated with erythrocyte sedimentation rate, and serum sICAM-1 level was positively correlated with anti-dsDNA antibody and IgG level (all P<0.05). ②The expression of ICAM-1 on the surface of CD4+ T cells and the level of sICAM-1 in the supernatant of healthy people were significantly up-regulated gradually along with the stimulation α-CD3/28. ③After co-culture, the IgG level in the supernatant of the stimulation group was higher than that in the control group, while IgG lever in antibody blockade group was lower than that in the stimulation group (both P<0.05).

    Conclusion

    ·ICAM-1 can promote the production of IgG after the interaction of CD4+ T cells and B cells, which can be used as a potential target for the treatment of SLE.

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    Cell-penetrating peptide Penetratin-modified liposomes for ophthalmic application: construction and in vitro evaluation
    Nan XU, Shu-yue ZHANG, Xue-ying DING
    2021, 41 (5):  595-602. 
    doi: 10.3969/j.issn.1674-8115.2021.05.006

    Abstract ( 204 )   HTML ( 21 )   PDF (3672KB) ( 122 )  
    Objective

    ·To prepare the cell-penetrating peptide Penetratin-modified liposome (Pen-Lip) for ophthalmic application and evaluate its applicability to treat fundus neovascularization diseases through topical instillation.

    Methods

    ·The copolymer DSPE-PEG2000-Pen was synthesized by the addition reaction of DSPE-PEG2000-Mal and Penetratin, and Pen-Lip was then prepared by the thin film dispersion method. The cellular uptake experiment was used to determine the optimal ratio of Penetratin to modify liposomes. The average particle size, Zeta potential and polydispersity index (PDI) of Pen-Lip were characterized by the nano particle size potentiometer, and the morphology of Pen-Lip was observed by using transmission electron microscope (TEM). The encapsulation efficiency and the drug loading of Pen-Lip with conbercept were determined by centrifugation. Pen-lip was incubated in the PBS or the PBS containing 50% fetal bovine serum for 48 h and the stability of Pen-Lip was investigated by the change of particle size and the morphology under TEM. The CCK-8 assay was conducted to detect the cytotoxicity of Pen-Lip to human corneal epithelial cell (HCEC) and human retinal pigment epithelium (ARPE-19), and the uptake of Pen-Lip by ARPE-19 was observed by using laser confocal microscope. The diffusion cell device was used to detect the permeability of Pen-Lip through the isolated rabbit cornea, and the apparent permeability coefficient (Papp) was calculated. The toxicity of Pen-Lip with conbercept to the corneal tissue was evaluated by the hydration value.

    Results

    ·The optimal ratio of Penetratin to modify liposomes was 3%. The average particle size of Pen-Lip was (148.07±3.51) nm, the Zeta potential was (5.66±0.91) mV, and the PDI was 0.227±0.045. TEM results showed that Pen-Lip had a smooth spherical structure. The encapsulation efficiency of Pen-Lip was (44.06±3.70) %, and the drug loading was (2.84±0.24) %. The particle size of Pen-Lip did not change significantly and TEM showed uniform dispersion after dispersing in the PBS or the PBS containing 50% fetal bovine serum for 48 h, exhibiting the good stability of Pen-Lip. When Pen-Lip was at the concentration of 15?500 μg/mL, Pen-Lip had no cytotoxicity to HCEC and ARPE-19. Compared with unmodified liposomes, ARPE-19 cells had significantly higher uptake of Pen-Lip (P=0.000). In the experiment of rabbit cornea penetration in vitro, the Papp of Pen-Lip was significantly higher than that of unmodified liposomes (P=0.000). There was no statistically significant difference in the hydration value of the rabbit cornea treated with drug-loaded Pen-Lip compared to the untreatd group (P>0.05).

    Conclusion

    ·Pen-Lip has good stability, biocompatibility and corneal permeability in vitro and can be taken up by retinal cells, which is a potential ocular drug delivery system to treat fundus neovascularization diseases through topical instillation.

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    Effect of oridonin up-regulating PLK1 on the cell cycle of Jurkat cells
    Wei HE, Yong ZUO
    2021, 41 (5):  603-611. 
    doi: 10.3969/j.issn.1674-8115.2021.05.007

    Abstract ( 249 )   HTML ( 13 )   PDF (3197KB) ( 94 )  
    Objective

    ·To explore the inhibitory effect of oridonin on the proliferation of Jurkat cells and its mechanism.

    Methods

    ·CCK-8 method, flow cytometry, Swiss Giemsa staining, and Western blotting were used to detect the proliferation, cell cycle and apoptosis of Jurkat cells and the expression of mitosis-related protein kinases after oridonin treatment. Western blotting was used to detect the phosphorylation level of PLK1 downstream proteins in Jurkat cells after oridonin treatment. Computer simulation, immunoprecipitation, Western blotting and Celluar Thermal Shift Assay were used to study the binding mode and binding site of oridonin and PLK1. Student's-t test was performed for comparison between each two groups. Statistical significance was accepted at a value of P<0.05.

    Results

    ·Oridonin could induce G2/M phase arrest in Jurkat cells by up-regulating the content of PLK1 protein and promoting its kinase activity. Oridonin could directly bind to PLK1 protein to inhibit its degradation through the ubiquitin proteasome pathway. The mutation of Cys67 or Cys133 amino acid residues of PLK1 protein inhibited its direct binding to oridonin. And the mutation inhibited the stabilizing effect of oridonin on PLK1 protein.

    Conclusion

    ·Oridonin inhibits PLK1 protein ubiquitination modification and degradation by directly binding to its protein. Oridonin can also promote PLK1 protein kinase activity and induce G2/M phase arrest in Jurkat cells. The Cys67 and Cys133 sites of the PLK1 protein are the key sites for the protein to bind to oridonin.

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    Clinical research
    Evaluative value of plasma fibrin degradation product in early prognosis of patients with hemorrhagic stroke
    Xu-guang CHEN, Sheng-yi SHI, Lan HU, Yu CHEN, Yi-ming LU, Jing YE
    2021, 41 (5):  612-616. 
    doi: 10.3969/j.issn.1674-8115.2021.05.008

    Abstract ( 244 )   HTML ( 7 )   PDF (1522KB) ( 75 )  
    Objective

    ·To investigate the value of plasma fibrin degradation product (FDP) in assessing the risk of death within 14 d after hemorrhagic stroke (HS) onset.

    Methods

    ·The general information, baseline laboratory parameters, surgical conditions and 14-day prognosis information of the patients with HS admitted to the Department of Emergency, North Branch of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from May 1, 2017 to May 1, 2020 were retrospectively studied to analyze the factors associated with the patients' 14-day prognosis, and multivariate Logistic regression analysis was performed. The patients were then divided into intracerebral hemorrhage (ICH) group, primary intraventricular hemorrhage (PIVH) group and subarachnoid hemorrhage (SAH) group; the ICH group was divided into four subgroups, i.e., simple hematoma subgroup, ICH+intraventricular hemorrhage (IVH) subgroup, ICH+SAH subgroup, and ICH+IVH+SAH subgroup. Differences in the plasma FDP level between the patients who died and those who survived within 14 d were analysed separately for each group and subgroup.

    Results

    ·A total of 606 patients with HS were included, with an average age of (58.9 ± 15.1) years, including 405 males and 201 females. There were 493 cases in the ICH group, 32 cases in the PIVH group and 81 cases in the SAH group; in the ICH group, 254 cases were in the simple hematoma subgroup, 142 cases were in the ICH+IVH subgroup, 49 cases were in the ICH+SAH subgroup and 48 cases were in the ICH+IVH+SAH subgroup. A total of 124 patients received surgical treatment. Eighty-five patients died within 14 d of onset. The plasma FDP level [2.07 (0.92, 5.65) μg/mL] was significantly higher in the patients who died within 14 d compared with those who survived [1.12 (0.70, 2.23) μg/mL] (P=0.000), and multivariate Logistic regression analysis showed that plasma FDP>2.78 μg/mL was an independent risk factor for death within 14 d (OR=2.564, P=0.001). Group analysis revealed that the plasma FDP level of the dead patients were significantly higher than those of the surviving patients in both the ICH group [2.09 (1.00, 5.34) μg/mL vs 1.06 (0.70, 1.86) μg/mL, P=0.000] and the PIVH group [4.25 (1.49, 5.91) μg/mL vs 1.20 (0.64, 2.30) μg/mL, P=0.041]. Subgroup analysis revealed that in the ICH+IVH subgroup, the plasma FDP level of the dead patients [2.09 (1.00, 5.58) μg/mL] was significantly higher than that of the surviving ones [1.26 (0.90, 2.21) μg/mL, P = 0.027].

    Conclusion

    ·Plasma FDP>2.78 μg/mL may predict a higher risk of death within 14 d in the patients with HS, especially in those with PIVH or ICH combined with IVH.

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    Diagnostic value of preablative stimulated thyroglobulin for recurrence or metastases of differentiated thyroid carcinoma complicated with nodular goitre
    Hong CHAI, Qin HUANG, Ze-quan CHEN, Jia-huan YANG, Yong-li YU
    2021, 41 (5):  617-621. 
    doi: 10.3969/j.issn.1674-8115.2021.05.009

    Abstract ( 216 )   HTML ( 8 )   PDF (1172KB) ( 65 )  
    Objective

    ·To evaluate the role of preablative stimulated thyroglobulin (ps-Tg) as an early prognostic marker for patients with differentiated thyroid carcinoma (DTC) complicated with nodular goitre (NG) after operation and determine the corresponding cut-off value.

    Methods

    ·A total of 268 patients with DTC complicated with NG who underwent the 131I treatment and thyroidectomy were analyzed. Logistic regression analysis were performed to evaluate baseline ps-Tg and other clinicopathologic characteristics in the prediction of distant metastasis. The receiver operating characteristic (ROC) curve analysis was conducted to analyze optimal cut-off point of ps-Tg for predicting the recurrence or metastasis for patients with DTC complicated with NG.

    Results

    ·In the Logistic analysis, ps-Tg (OR=1.002, P=0.005), N1b (OR=0.235, P=0.001) and the histological-pathological types (OR=0.263, P=0.012) were predictors of distant metastasis. The cut-off value of ps-Tg for predicting the recurrence or metastasis was 26.97 ng/mL, with sensitivity of 66.7% and specificity of 83.3%. Area under the ROC curve was 0.795.

    Conclusion

    ·For patients with DTC complicated with NG, ps-Tg, N1b and the histological- pathological types have a significant prognostic implication in early postoperative metastasis or recurrence. The cut off value of ps-Tg could be more useful for the prediction of metastasis or recurrence.

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    Effects of computerized cognitive correction therapy on cognitive function of schizophrenia
    Guo-qin HU, Cheng-qing YANG, Qin-yu LÜ, Jing ZHAO, Ming-huan ZHU, Zheng-hui YI, Xin-hai DAI
    2021, 41 (5):  622-627. 
    doi: 10.3969/j.issn.1674-8115.2021.05.010

    Abstract ( 295 )   HTML ( 11 )   PDF (1204KB) ( 182 )  
    Objective

    ·To explore the effects of computerized cognitive correction therapy (CCRT) on the cognitive function of patients with chronic schizophrenia and the effects on plasma brain-derived nerve growth factor (BDNF) and tyrosine kinase receptors B (TrK-B) .

    Methods

    ·162 patients with chronic schizophrenia from Shanghai Mental Health Center of Huangpu District were randomly divided into CCRT group and control group according to the random number table method. 81 patients in the control group were treated with the conventional antipsychotic drugs, and 81 patients in the CCRT group were given CCRT combined with the conventional antipsychotic treatment. The period of treatments is 12 weeks. The cognitive function by Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), detection of plasma BDNF and TrK-B expression levels by avidinbiotincomplex-Enzyme Linked Immune Sorbent Assay (ABC-ELISA) were assessed at the baseline and at the end of the 12th week. Paired sample t-test was applied to compare the cognitive function, plasma BDNF and TrK-B protein expression levels in the baseline between the two groups, and the repeated measurements variance analysis was used to compare the cognitive function and plasma BDNF and TrK-B protein expression levels between the two groups after treatment and change within the group. The correlation between the improvement of cognitive function and the change of protein expression levels used a general linear model.

    Results

    ·The CCRT group and the control group actually completed 77 cases each. At the baseline, there was no statistically significant difference among cognitive function, BDNF and TrK-B between the two groups; after 12 weeks of treatment, cognitive function (P=0.000), BDNF (P=0.007) and TrK-B (P=0.015) expression level was statistically different between the CCRT and the control group; for CCRT group, cognitive function (P=0.000), BDNF (P=0.002) and TrK-B (P=0.000) expression level was significantly different after 12 weeks of treatment compared with the baseline, but not in the control group. The change of BDNF protein expression level is significantly correlated with the improvement of vocabulary learning (r2=1.598, P=0.019), story retelling (r2=1.495, P=0.038), digital breadth (r2=1.855, P=0.004), story recall (r2=1.459, P=0.047) and attention function (r2=1.673,P=0.012). The change of TrK-B protein expression level is significantly correlated with the improvement of picture naming (r2=1.582, P=0.034).

    Conclusion

    ·The use of CCRT in the adjuvant treatment of antipsychotic treatment for schizophrenia patients has a significant effect on cognitive function. The improvement of some cognitive functions are significantly related to the changes in the plasma BDNF and its TrK-B expression levels.

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    Clinical features of 119 old patients with respiratory virus infection
    Dao HUANG, Dong WEI, Zhi-hong XU, Jia-an HU
    2021, 41 (5):  628-631. 
    doi: 10.3969/j.issn.1674-8115.2021.05.011

    Abstract ( 262 )   HTML ( 7 )   PDF (974KB) ( 64 )  
    Objective

    ·To analyze the clinical features and risk factors that possibly affect the clinical outcome of elderly patients with respiratory virus infection.

    Methods

    ·A total of 119 hospitalized patients (≥65 years old) with respiratory virus infection in the Department of Geriatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine were enrolled in this study. The clinical symptoms, laboratory examination, treatment course and outcome were analyzed and compared between cured patients and dead patients.

    Results

    ·The average age of the patients was (85.61±7.67) years old, the male to female ratio was 98∶21 and 12 cases were dead. The number of influenza A virus patients (41 cases) was the most. Compared with cured patients, the dead patients were older, and the proportion of cases with bacterial infection or with double pneumonia in chest CT was higher (P<0.05). In the laboratory examination on admission, there were significant differences between the cured patients and the dead patients on leukocyte count, neutrophil count, erythrocyte count, the levels of hemoglobin, serum albumin, urea, and creatinine, and estimated glomerular filtration rate (P<0.05).

    Conclusion

    ·Older age, higher leukocyte count and neutrophil count, lower hemoglobin and albumin levels, renal insufficiency and bacterial infection may be the influencing factors of death in elderly patients with respiratory virus infection.

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    Analysis of clinical characteristics of 283 maternal near miss admitted to intensive care unit
    Yi-jun HOU, Yun XIE, Tao WANG, Pei-jie HUANG
    2021, 41 (5):  632-636. 
    doi: 10.3969/j.issn.1674-8115.2021.05.012

    Abstract ( 225 )   HTML ( 4 )   PDF (1126KB) ( 84 )  
    Objective

    ·To explore the clinical characteristics and mortality of maternal near miss admitted to intensive care unit (ICU).

    Methods

    ·A total of 283 maternal near miss admitted to ICU of Southern District of Shanghai General Hospital, Shanghai Jiao Tong University from January 2007 to December 2018 were selected. According to whether the main cause of ICU admission was related to pregnancy, the patients were divided into pregnancy complication group (175 cases) and pregnancy comorbidity group (108 cases). Statistical methods were used to compare the differences of the clinical data between the two groups.

    Results

    ·The top three diseases in the pregnancy complication group were hypertensive disorders complicating pregnancy, obstetric hemorrhage and metabolic disorders caused by hyperemesis gravidarum. The top three diseases in the pregnancy comorbidity group were pregnancy with heart disease, infection and acute pancreatitis. Compared with the pregnancy comorbidity group, the average age of pregnant and postpartum women in the pregnancy complication group was older, the number of multipara and irregular birth examination were more, Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) was higher, and the number of medical puncture procedure (thoracentesis, abdominocentesis, lumbar puncture and bone marrow puncture) was less (all P<0.05).

    Conclusion

    ·There are many causes of ICU admission for maternal near miss. In-depth analysis of the clinical characteristics of this kind of pregnant women will help ICU physicians better understand and manage acute critical illness in obstetrics.

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    Feasibility of non-opioid analgesic in breast-conserving surgery under general anesthesia with laryngeal mask airway
    Hoiyin CHEUNG, Xiao-ying CHU
    2021, 41 (5):  637-641. 
    doi: 10.3969/j.issn.1674-8115.2021.05.013

    Abstract ( 244 )   HTML ( 4 )   PDF (1098KB) ( 85 )  
    Objective

    ·To study the feasibility of not using opioids in breast-conserving surgery under general anesthesia with laryngeal mask airway.

    Methods

    ·Forty female patients who underwent breast-conserving surgery for breast cancer were selected and randomly divided into an experimental group and a control group by random number table method, twenty cases in each. The experimental group underwent ultrasound-guided pectoral nerve block and serratus anterior plane block (SAPB) before induction, combined with dexmedetomidine and nonsteroidal anti-inflammatroy drug (NSAID) during the operation, and did not use opioids. The control group was given opioids without nerve block. The rest of the drugs were the same in both groups. The hemodynamic changes (systolic blood pressure, diastolic blood pressure and mean arterial pressure) of the patients at six time points were observed: before induction (T0), start induction (T1), 5 min after induction (T2), 10 min after induction (T3), incision (T4), and 5 min after incision (T5). The use of vasoactive agent, operation time, the recovery time of spontaneous breathing, laryngeal mask removal time, postoperative nausea, postoperative vomiting, postoperative delirium and visual analogue score (VAS) of patients in resuscitation room at rest and during activity, postoperative VAS at 6 h (at rest and during activity), and postoperative VAS at 24 h (at rest and during activity) between the two groups were compared.

    Results

    ·The differences in systolic blood pressure, diastolic blood pressure and mean arterial pressure between the two groups at time points T3 and T5 were statistically significant (all P<0.05). The differences in heart rate at time points T3, T4 and T5 were statistically significant (all P<0.05). One patient in the experimental group used vasoactive agent and six patients in the control group used vasoactive agent. No statistical difference was found between the recovery time of spontaneous breathing and laryngeal mask removal time in the two groups. No patients in the experimental group experienced postoperative nausea and vomiting. In the control group, two patients had nausea, and another two patients had nausea and vomiting. The resting VAS at 6 h after surgery in the experimental group was higher than that in the control group, and the result had statistical significance (P<0.05). Four patients in the experimental group took oral analgesic after surgery, and no patients in the control group used oral analgesic after surgery.

    Conclusion

    ·Pectoral nerve block, and SAPB combined with dexmedetomidine and NSAID under ultrasound make it possible not to use opioids during breast-conserving surgery under general anesthesia with laryngeal mask airway. The postoperative analgesic effect needs to be improved.

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    Evidence-based medicine
    Meta-analysis of efficacy and safety of left atrial appendage closure and oral anticoagulants in atrial fibrillation
    Yan-xia REN, Zhi-jing AN, De-mei ZHANG, Xue-ya GUO
    2021, 41 (5):  642-647. 
    doi: 10.3969/j.issn.1674-8115.2021.05.014

    Abstract ( 241 )   HTML ( 4 )   PDF (2043KB) ( 64 )  
    Objective

    ·To evaluate the efficacy and safety of left atrial appendage closure (LAAC) and oral anticoagulants [warfarin and novel oral anticoagulants(NOAC)] in non-valvular atrial fibrillation (AF).

    Method

    ·The related articles were obtained from PubMed, Embase, Cochrane Library, Wanfang database and CNKI, from the establishment of databases to July 2020. English retrieval method was as follows: ("atrial fibrillation" or "AF" or "nonvalvular AF") and ("left atrial appendage closure" or "LAAC") and ("new oral anticoagulants" or "NOAC" or "novel oral anticoagulants" or "non-vitamin K antagonist oral anticoagulants" or "warfarin"). Chinese keywords were "心房颤动""左心耳封堵术""新型口服抗凝剂" and "华法林". The articles were screened according to inclusion and exclusion criterias, and the quality evaluation and data extraction were carried out. The RevMan 5.3 software was used for meta-analysis of the data. The primary efficacy and safety endpoints were the incidence of embolism events, bleeding events, all-cause mortality events and sudden cardiac death (SCD).

    Results

    ·Finally, nine articles was included, including three randomized controlled trials and six non-randomized controlled trials, consisting of 2 429 patients. The result of meta-analysis showed that there was no significant difference in compound embolism events in patients with AF treated with LAAC, compared with oral anticoagulant therapy (OR=0.90, 95%CI 0.62?1.31, P=0.59). There was no significant difference in all-cause mortality events in patients with AF treated with LAAC, compared with oral anticoagulant therapy (OR=1.11, 95%CI 0.48?2.59, P=0.81). There was no significant difference in SCD patients with AF treated with LAAC, compared with oral anticoagulant therapy (OR=0.90,95%CI 0.38?2.11, P=0.81). Compared with warfarin and NOAC, the incidence of bleeding events in patients treated with LAAC was decreased significantly (OR=0.48, 95%CI 0.35?0.65, P=0.000).

    Conclusion

    ·There is no significant difference in embolism and death in patients of non-valvular AF treated with LAAC, compared with oral anticoagulants. But it has a lower risk of bleeding.

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    Public health
    Spatio-temporal analysis of incidence rate of syphilis in China
    Ting-ting TIAN, Ya-xuan HOU, Yu-qing LI, Hong-jiao QI, Mo CHEN, Mei-xia LÜ
    2021, 41 (5):  648-652. 
    doi: 10.3969/j.issn.1674-8115.2021.05.015

    Abstract ( 410 )   HTML ( 16 )   PDF (1308KB) ( 333 )  
    Objective

    ·To get the spatio-temporal distribution of the syphilis epidemic in 31 provinces, municipalities directly under the Central Government and autonomous regions of the mainland of China in 2017.

    Methods

    ·The data of syphilis incidence in 31 provinces, municipalities and autonomous regions of the mainland of China in 2017 were obtained from the China Public Health Science Data Center, and the time distrbution characteristics of the incidence rates were described. The global Moran′s I index and Anselin local Moran′s I index were used to analyze the spatial cluster characteristics of the syphilis cases, and then space-time scan analysis based on Poisson distribution was used to explore the spatio-temporal distribution characteristics.

    Results

    ·In 2017, the number of syphilis cases in the 31 provinces, municipalities, and autonomous regions of the mainland of China was 475 860, and the incidence rate was 34.49/100 000. Latent syphilis accounted for most of the cases, reaching 76.78% (365 353/475 860). August had the highest incidence rate. For the spatial distribution, Xinjiang Uygur Autonomous Region was the provincial-level unit with the highest incidence rate of syphilis, reaching 91.80/100 000. The incidence rates of latent, secondary, tertiary, and congenital syphilis appeared with positive spatial autocorrelation (all P<0.05). The high-high clusters of secondary and tertiary syphilis appeared in Shanghai, Jiangsu, and Zhejiang (all P<0.05), respectively, while the high-high clusters of congenital syphilis appeared in Xinjiang and Tibet (P=0.000). The results of space-time scan analysis showed that the main cluster appeared from April to September in Fujian, Jiangxi, Zhejiang, Shanghai, Jiangsu, Hunan, Anhui, and Guangdong (P=0.000). Compared with the outside area, the relative risk of syphilis in this cluster was 1.59 times.

    Conclusion

    ·The incidence rate of syphilis in China is relatively high. There are differences in the types and periods of syphilis prevention and control among provinces, municipalities and autonomous regions. From April to September, Fujian, Jiangxi, Zhejiang, Shanghai, Jiangsu, Hunan, Anhui and Guangdong are the key areas for syphilis prevention and control in the mainland of China.

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    Review
    Short- and long-term effects of frozen-thawed embryo transfer on offspring
    Ning-xin QIN, Wen-long ZHAO, Zhi-yang ZHOU, Wei-hui SHI, Yan-ting WU, He-feng HUANG
    2021, 41 (5):  653-658. 
    doi: 10.3969/j.issn.1674-8115.2021.05.016

    Abstract ( 253 )   HTML ( 8 )   PDF (1135KB) ( 107 )  

    Frozen-thawed embryo transfer (FET) is one of the commonly used assisted reproductive technology. Because FET has the advantages of high cumulative pregnancy rate and low incidence of ovarian hyperstimulation syndrome, the number of offspring born through this technology is increasing year by year. Many studies have shown that the risks of preterm delivery, low birth weight and small for gestation age of FET offspring are lower than those of the offspring born in the fresh embryo transfer cycle. There is also evidence that the risks of macrosomia and large for gestational age of FET offspring are higher. At the same time, there are also reports on the long-term health status of FET offspring in childhood and adulthood. This paper reviews the short-term and long-term effects of FET on offspring and the causes.

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    Mechanisms related to regulation of natural killer cell activity by exosomes derived from malignant tumor cells
    Ting-wei LU, Jian-jun ZHANG, Wan-tao CHEN
    2021, 41 (5):  659-664. 
    doi: 10.3969/j.issn.1674-8115.2021.05.017

    Abstract ( 237 )   HTML ( 5 )   PDF (1175KB) ( 122 )  

    Exosomes are a kind of extracellular vesicles that play the role of transmitting information among cells. Through transporting of substances to regulate the physiological and pathological functions of various cells, it can affect the progress of malignant tumors. Natural killer (NK) cell is an indispensable part of the human immune system, and is important in the development of cancers. In the tumor microenvironment, tumor-derived exosomes (TDEXs) can act on NK cells, adjusting their functions, and modifying the interaction between NK cells and other immune cells, resulting in the change of the immune response. In recent years, the research on the relationship between NK cells and tumor exosomes has become a hot topic. The effects of TDEXs from different cancers on the activities of NK cells are summarized in this paper.

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    Relationship between non-coding RNAs and vascular diseases of diabetes mellitus
    Shu-jun WAN, Xiang KONG, Kun LÜ
    2021, 41 (5):  665-670. 
    doi: 10.3969/j.issn.1674-8115.2021.05.018

    Abstract ( 246 )   HTML ( 11 )   PDF (1110KB) ( 74 )  

    Non-coding RNAs (ncRNAs) are a class of molecules that do not encode protein. As important biological regulatory factors, they can affect the occurrence and development of vascular diseases of diabetes mellitus (DM) at the levels of transcription and post-transcription. ncRNAs mainly include microRNAs (miRNAs), long non coding RNAs (lncRNAs) and circular RNAs (circRNAs) according to their fragment sizes. miRNAs can regulate target gene expressions at the post-transcriptional level and have the potential to be their clinical markers. lncRNAs affect a variety of molecular signaling pathways. The role of lncRNAs in vascular diseases of DM has attracted increasing attention in recent years. circRNAs possess significant capabilities of gene regulation and could participate in pathological process of DM by competing with miRNAs for binding sites. To develop new ideas for the diagnosis and treatment of vascular diseases of DM, a brief review of the current research on ncRNAs and DM angiopathy is provided.

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    Research progress in the systemic treatment for breast cancer with brain metastasis
    Jia-ling ZHANG, Feng-chun ZHANG, Ying-chun XU
    2021, 41 (5):  671-677. 
    doi: 10.3969/j.issn.1674-8115.2021.05.019

    Abstract ( 266 )   HTML ( 22 )   PDF (1305KB) ( 127 )  

    Breast cancer is one of the most common malignancies in women. Brain metastases occur in approximately 10%–20% of patients with advanced breast cancer. In recent years, with the rapid progress of systemic treatment, extracranial lesions have been effectively controlled and the survival time of patients with breast cancer have been prolonged. Thus the possibility of developing brain metastases has been increased. Moreover, advances in modern diagnostic imaging technology and the routine surveillance of cancer patients have increased the detection rate of brain lesions. Based on the above two aspects, the breast cancer brain metastases (BCBM) have become increasingly common in the clinical settings. Because many chemotherapeutic drugs can not penetrate the blood-brain barrier, the patients with brain metastases have less treatment options, worse survival outcomes and lower quality of life. This article focuses on the recent advances in systemic treatment for BCBM, aiming to provide reference for basic research and clinical practices of this disease.

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    Research progress of osteosarcopenia
    Miao-miao CAI, Yan-hong GAO
    2021, 41 (5):  678-683. 
    doi: 10.3969/j.issn.1674-8115.2021.05.020

    Abstract ( 346 )   HTML ( 6 )   PDF (1172KB) ( 159 )  

    Osreosarcopenia is a geriatric syndrome that describes the co-existence of osteoporosis and sarcopenia, which is widespread in the elderly. Osteoporosis is a condition of low bone mass and micro-architectural of bone, and sarcopenia, the loss of muscle mass, strength and muscle physiological functions. Sarcopenia and osteoporosis are age-related degenerative diseases with similar pathophysiology, including mechanical factors, genetics, fatty infiltration and endocrine factors. Studying the pathogenesis of sarcopenia-osteoporosis is of great significance in preventing and treating the disease, improving the quality of life and physical and mental health of the elderly. This review introduces the diagnosis, pathogenesis, intervention and treatment of osteosarcopenia.

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    Function of human nucleic acid alkylation damage repair enzyme ALKBH3 in cancer progression and oncotherapy
    Jing-yan HU, Lin ZHANG, Liang ZHANG
    2021, 41 (5):  684-689. 
    doi: 10.3969/j.issn.1674-8115.2021.05.021

    Abstract ( 242 )   HTML ( 4 )   PDF (1859KB) ( 106 )  

    Human nucleic acid alkylation damage repair enzyme ALKBH3 (alpha-ketoglutarate-dependent dioxygenase homolog 3) belongs to Fe2+/α-Ketoglutarate (α-KG)-dependent AlkB dioxygenase family, and shares a highly conserved catalytic domain through the entire family. ALKBH3 specifically recognizes N1-methyl adenine and N3-methyl cytosine on single-stranded DNA or RNA, and catalyzes their methyl group removal for alkylation damage repair. Previous studies have shown that ALKBH3 is highly expressed in various solid tumors, and thereby it has been considered as a potential anti-tumor drug target. Research of the structural function and regulation mechanism of ALKBH3 will help further understand the molecular mechanism in the DNA alkylation damage repair, and lay the foundation for the development of anti-tumor drugs targeting ALKBH3.

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    Research progress in animal model of acute lung injury
    Jing-yi FU, Lei WANG, Yi YANG
    2021, 41 (5):  690-694. 
    doi: 10.3969/j.issn.1674-8115.2021.05.022

    Abstract ( 335 )   HTML ( 17 )   PDF (1153KB) ( 198 )  

    Acute lung injury (ALI) refers to the occurrence of hypoxic respiratory failure and even acute respiratory distress syndrome caused by various factors. The morbidity and fatality rate of ALI are very high, but the research on its pathogenesis and treatment methods has not made much progress. Therefore, it is very necessary to establish animal models to simulate acute lung injury. In this paper, the literature on animal models of ALI in recent years is collected and summarized, and the selection of animal models of acute lung injury and the evaluation methods of lung injury are reviewed, so as to provide reference for the establishment of animal models of ALI.

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    Techniques and methods
    Image-fusion-based surgical navigation in sclerotherapy for low-flow vascular malformations in the risky regions of head and neck
    Hao GU, Xi YANG, Zi-min ZHANG, Yun-bo JIN, Li HU, Hui CHEN, Xiao-xi LIN
    2021, 41 (5):  695-700. 
    doi: 10.3969/j.issn.1674-8115.2021.05.023

    Abstract ( 167 )   HTML ( 6 )   PDF (3290KB) ( 87 )  
    Objective

    ·To evaluate the feasibility and safety of image-guided surgical navigation, a real-time stereotactic guidance technique, in sclerotherapy of low-flow vascular malformations in the risky regions of head and neck.

    Methods

    ·The patients with low-flow vascular malformations in the heads or necks who underwent surgical navigation-assisted sclerotherapy in the Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine were retrospectively included. The preoperative CT images and magnetic resonance images were fused to design the puncture trajectory. During the operation, the navigation system was used to puncture according to the designed path, and the results were verified by digital subtraction angiography. The technical success rate of intralesional needle placement and postoperative complications were analyzed.

    Results

    ·A total of 19 procedures for 30 lesions performed on 10 patients with low-flow vascular malformations (6 cases with intraorbital lesions, and 4 cases with pharyngeal lesions) were included. The average age of initial procedure was 20.9 years. The technical success rate was 80.0% (24/30). No other complications were observed except a case of pneumonia caused by sclerosing agent-induced glottic ulcer after one procedure.

    Conclusion

    ·Image-guided surgical navigation is a feasible and safe auxiliary technique for the lesions in the risky regions of head and neck.

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