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    Mechanism of MUC1 in the pathogenesis of HER2-positive breast cancer
    Cheng-zhi WANG, Hua-yun DENG, Zhi PANG, Lei HUANG
    2021, 41 (7):  839-848. 
    doi: 10.3969/j.issn.1674-8115.2021.07.001

    Abstract ( 139 )   HTML ( 28 )   PDF (9542KB) ( 36 )  
    Objective

    ·To study the role and mechanism of mucin 1 (MUC1) in the pathogenesis of HER2-positive breast cancer.

    Methods

    ·Virus infection technology was employed to construct MT2/MUC1 and MT2/Vec/MUC1-CD overexpression cell lines; Western blotting was used to detect the expression level of relative proteins; the ability of cell proliferation, migration and sphere formation were detected by using cell counting kit-8 (CCK-8), colony formation, wound healing, transwell and sphere formation experiments respectively; inhibitor 6-AN was used to inhibit glucose-6-phosphate 1-dehydrogenase (G6PD) activity, and the proliferation of breast cancer cells was detected by CCK-8. GEPIA and Kaplan-Meier Plotter database were analyzed to figure out the relationship of HER2, MUC1 and G6PD expression with the survival of breast cancer patients.

    Results

    ·Overexpression of MUC1 or MUC1-CD promoted the proliferation, clone formation, migration and sphere formation of MT2 HER2-positive breast cancer cells, as well as elevating the protein level of G6PD. Inhibition of G6PD activity significantly reduced cell proliferation induced by MUC1 and MUC1-CD. High level of G6PD protein in breast cancer tissues is associated with significantly lower survival of breast cancer patients.

    Conclusion

    ·MUC1 may promote the progression of HER2-positive breast cancer by up-regulating the expression of G6PD, suggesting that inhibition of the pentose phosphate pathway may be a target for the treatment of HER2-positive breast cancer.

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    Basic research
    Promotive effect of antitumor drug etoposide on osteogenic differentiation of mesenchymal stem cells
    Yan-qing LU, Xing ZHOU, Jiao LI, Jian-ping PENG, Chuan-dong WANG, Xiao-ling ZHANG
    2021, 41 (7):  849-857. 
    doi: 10.3969/j.issn.1674-8115.2021.07.002

    Abstract ( 138 )   HTML ( 8 )   PDF (4957KB) ( 41 )  
    Objective

    ·To study the effect and possible mechanism of the anti-tumor drug etoposide in promoting osteogenic differentiation of mesenchymal stem cells (MSCs).

    Methods

    ·Primary cultured MSCs were isolated from the bone marrow of C57BL/6J mice and humans. After the mouse MSCs were given different concentrations (0?12.50 μmol/L) of etoposide for 12, 24, 36, 48 and 60 h, the cell proliferation ability was detected by CCK-8 kit assay. The apoptosis detection kit was performed to detect apoptosis of osteoblast/osteosarcoma cell line UMR-106 treated by etoposide (0, 0.001, 0.01, 0.1, 1 μmol/L). The mouse and human MSCs (simultaneously inducing osteogenic differentiation), and UMR-106 cells were treated with etoposide (0, 0.001, 0.01, 0.1, 1 μmol/L), whose osteogenic differentiation was analyzed by alkaline phosphatase (ALP) staining and alizarin red staining. The mRNA levels of osteogenic differentiation markers i.e., Alp, osteocalcin, and collagen type Ⅰ α 1 chain were analyzed by real-time quantitative PCR. After the UMR-106 cells were treated with etoposide (0.001 μmol/L), Illumina Xten′s high-throughput transcriptome sequencing and bioinformatics analysis were used to find the target gene related with osteogenic differentiation, which was then verified by PCR. Western blotting was used to detect the expression of osterix (OSX), runt-related transcription factor 2 (RUNX2) and DNA binding inhibitor 1 (ID1) in the etoposide (0, 0.001, 0.01, 0.1, 1 μmol/L) treated mouse MSCs.

    Results

    ·The effect of etoposide on the proliferation of mouse MSCs was concentration-dependent. When the concentration was ≥0.20 μmol/L, etoposide inhibited the proliferation of MSCs. The half-maximal inhibitory concentrations (IC50) for 48 h and 60 h were 2.192 μmol/L and 1.399 μmol/L, respectively. Apoptosis detection results showed that the apoptotic rates of UMR-106 cells treated with 0.001?1 μmol/L etoposide were 16.137%?28.300%. The results of ALP staining, alizarin red staining and PCR showed that etoposide at 0.001?0.1 μmol/L significantly promoted the osteogenic differentiation of mouse and human MSCs and UMR-106 cells. RNA sequencing analysis showed that etoposide up-regulated connective tissue growth factor expression in the UMR-106 cells. Western blotting results showed that 0.001 and 0.01 μmol/L etoposide significantly increased the protein expression of OSX, RUNX2 and ID1 in the mouse MSCs.

    Conclusion

    ·The anti-tumor drug etoposide can promote the osteogenic differentiation of MSCs, which may be related to the up-regulation of ID1, RUNX2 and OSX expressions.

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    Function of branched-chain amino acid catabolism in lung cancer cells
    Yan-qi HE, Rui CHI, Meng-ping CHEN, Si CHEN, Chun-liang LIU, Yun-xia LIU, Hai-peng SUN
    2021, 41 (7):  858-864. 
    doi: 10.3969/j.issn.1674-8115.2021.07.003

    Abstract ( 153 )   HTML ( 17 )   PDF (1757KB) ( 25 )  
    Objective

    ·To explore the function and mechanism of branched-chain amino acid (BCAA) catabolism in lung cancer cells.

    Methods

    ·Small interfering negative control (siNC) and small interfering branched-chain keto acid dehydrogenase kinase (siBCKDK) were transfected into non-small cell lung cancer cells H1299, A549 and HCC827 by instantaneous transfection. The expression of BCKDK, branched-chain keto acid dehydrogenase e1, α polypeptide (BCKDE1α) and its phosphorylation in siNC group and siBCKDK group were detected by Western blotting. The proliferation activity of the above two groups of cells was detected by CCK-8 assay. The above three kinds of cells were cultured in culture medium containing 0, 100, 200 μmol/L BT2 (3, 6-dichlorobenzo[b]thiophene-2-carboxylic acid), respectively. The expression of BCKDE1α and its phosphorylation were detected by Western blotting. The proliferation activity of 0 μmol/L BT2 group and 200 μmol/L BT2 group was detected by CCK-8 assay. The cell viability of siNC group and siBCKDK group, 0 μmol/L BT2 group and 200 μmol/L BT2 group in H1299 and A549 cells was calculated by trypan blue staining. Cell number at different phases of cell cycle was detected by propidium iodide staining. Cyclin-dependent kinase inhibitor 1A (P21) expression was detected by Western blotting.

    Results

    ·In H1299, A549 and HCC827 cells, compared with siNC group, expression of BCKDK and phosphorylation of BCKDE1α in siBCKDK group were down-regulated, and the proliferation activity was decreased (all P=0.000). Compared with 0 μmol/L BT2 group, the phosphorylation of BCKDE1α was down-regulated in H1299, A549 and HCC827 cells in both 100 μmol/L BT2 group and 200 μmol/L BT2 group, but more obviously in 200 μmol/L BT2 group. The cell proliferation activity in 200 μmol/L BT2 group was decreased compared with that in 0 μmol/L BT2 group (all P=0.000). There was no significant difference in the cell viability of H1299 and A549 cells between siBCKDK group and siNC group, 200 μmol/L BT2 group and 0 μmol/L BT2 group, but G0/G1 cell cycle arrest occurred (all P<0.05) with the expression of P21 increasing.

    Conclusion

    ·siBCKDK and BT2 can promote the dephosphorylation of BCKDE1α and accelerate the catabolism of BCAA, which may inhibit the proliferation of lung cancer cells by up-regulating P21 and blocking cell cycle.

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    Single-cell transcriptomic analysis of development and involution of human thymic stroma
    Yu-chen LI, Li-lian BAI, He-feng HUANG, Xin-mei LIU
    2021, 41 (7):  865-875. 
    doi: 10.3969/j.issn.1674-8115.2021.07.004

    Abstract ( 125 )   HTML ( 14 )   PDF (8764KB) ( 49 )  
    Objective

    ·To explore the transcriptomic dynamics of human thymic stroma cells across different developmental stages.

    Methods

    ·The single-cell transcriptome datasets of human thymus were downloaded from ArrayExpress (E-MATB-8581). The cellular maps of thymic stroma cells across different developmental stages were analyzed based on protein-protein interaction. The differentially expressed genes of fetal, infant and adult stages were calculated. The cell state alternation across different developmental stages was predicted based on functional enrichment analysis.

    Results

    ·The transcriptomic dynamics of thymic epithelial cells (TEC), endothelial cells (Endo) and fibroblasts (Fb) were more remarkable compared with dendritic cells. In adult thymus, there was decline of antigen presenting function and down-regulation of major histocompatibility complex (MHC) class Ⅱ genes in medullary TEC type Ⅰ cells. The fibroblasts enriched functions related to antigen recognition, differentiation and activation of T cells in postnatal thymus. The up-regulated genes of thymic Endo enriched functions such as extracellular matrix during fetal and infant stages, while up-regulated MHC genes and enriched pathways associated with antigen presenting in adult thymus.

    Conclusion

    ·Bioinformatics analysis revealed that mTEC, Fb and Endo were the susceptible stroma cell types in response to thymic development and senescence. The involution of human thymus may affect the negative selection of T cell differentiation mostly.

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    6-OHDA-induced Parkinson disease mice exhibit senescent phenotypes characterized by upregulation of p16Ink4a and astrocyte senescence
    Xiao YUAN, Ye-ye TIAN, Zheng XUE
    2021, 41 (7):  876-883. 
    doi: 10.3969/j.issn.1674-8115.2021.07.005

    Abstract ( 105 )   HTML ( 10 )   PDF (6857KB) ( 35 )  
    Objective

    ·To explore whether 6-hydroxydopamine(6-OHDA)-induced Parkinson disease (PD) mouse models have senescent phenotypes and explore the changes of senescence-related glial cells.

    Methods

    ·Thirty 9?10 months old C57BL/6J male mice were divided into Sham-operated group (n=15) and 6-OHDA group (n=15). PD mouse models were established by stereotactic injection of 6-OHDA into striatum. The neurological function deficit was evaluated by rotarod test and apomorphine (APO)-induced rotational behavior on the 21st day after modeling. The brain was taken after the last behavioral experiment. Western blotting was used to detect the protein content of tyrosine hydroxylase (TH) in both caudate putamen (CPu) and substantia nigra (SN) regions. Immunofluorescence was used to observe the expression of glial cells and aging marker p16Ink4a / p21 in both CPu and SN regions. RT-qPCR was also used to detect the expression and changes of cyclin-dependent kinase inhibitor including p16Ink4a, p15Ink4b, p19Ink4d, p21 and p27Kip1, and senescence-associated secretory phenotype including Cxcl10, Ccl2, tumor necrosis factor-α (Tnf-α), interleukin-1α (Il-1α), Il-1β, Il-6 and matrix metalloproteinase 3 (MMP3).

    Results

    ·The decreased falling latency in rotarod test (P=0.000), the increased number of rotations induced by APO (P=0.000) and the loss of TH protein measured by Western blotting (P=0.000), suggested that 6-OHDA unilateral striatum mouse model of PD was successfully established. Immunofluorescence staining showed that the upregulation of an aging marker p16Ink4a in both CPu and SN regions of the 6-OHDA group compared with the Sham group, but p21 was not significantly expressed in both groups; senescent astrocytes, microglia and oligodendrocytes were accumulated in CPu and SN regions as well, while the number of astrocytes was larger than the other two types of glia cells (P<0.05). RT-qPCR results showed that, compared with those of the Sham group, p15Ink4b, p16Ink4a and p19Ink4d in CPu and SN regions of the 6-OHDA group were up-regulated (P<0.05); p21 was slightly up-regulated, but the difference was not statistically significant (P?0.05); p27kip1 was slightly up-regulated, but statistically significant difference only presented in SN region (P=0.016). RT-qPCR also showed that, compared with those of the Sham group, the levels of Cxcl10, Ccl2, Il-1α and Il-6 were significantly up-regulated while Il-1β was significantly decreased in CPu region of the 6-OHDA group (P<0.05); the levels of Ccl2, Tnf-α, Il-1α and Il-6 were significantly increased while Mmp3 and Il-1β were significantly decreased in SN region of the 6-OHDA group (P<0.05).

    Conclusion

    ·6-OHDA-induced PD mice exhibit senescent phenotypes characterized by upregulation of p16Ink4a and astrocyte senescence.

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    Effect of miR-877-3p on proliferation of bone marrow mesenchymal stem cells in osteoporosis
    Xu TONG, Lin-jing SHU
    2021, 41 (7):  884-890. 
    doi: 10.3969/j.issn.1674-8115.2021.07.006

    Abstract ( 102 )   HTML ( 9 )   PDF (2836KB) ( 31 )  
    Objective

    ·To investigate the effect of miR-877-3p on the proliferation of bone marrow mesenchymal stem cells (BMSCs) during the occurrence and development of osteoporosis.

    Methods

    ·Twenty female healthy mice aged 8 weeks underwent bilateral ovariectomy to establish the postmenopausal osteoporosis models (OVX group). In addition, 20 healthy female mice were selected in the same period and the adipose tissue near the ovary was removed to establish sham operation models (Sham group). Two months after surgery, bone parameters of the mice, including bone volume fraction (BVF), trabecular number (Tb.N), and bone mineral density (BMD) were detected by micro-CT, and cell proliferation ability of the two groups was detected by CCK-8 and cell counting. The expression of miR-877-3p in the two groups was detected by real-time PCR. After up-regulating (down-regulating) the level of miR-877-3p in the BMSCs, cell proliferation was detected by CCK-8 and cell counting.

    Results

    ·The micro-CT results showed that there were significant differences in bone parameters between the Sham group and the OVX group (P<0.05). The results of CCK-8 and cell counting showed that the proliferation ability of BMSCs in the Sham group was significantly higher than that in the OVX group (P<0.05). Real-time PCR results showed that the expression of miR-877-3p in BMSCs in the Sham group was significantly lower than that in the OVX group (P<0.05). After upregulation (downregulation) of miR-877-3p, the proliferation ability of BMSCs decreased (increased).

    Conclusion

    ·In postmenopausal osteoporosis mice, the proliferation ability of BMSCs is regulated by miR-877-3p, which may be one of the important factors affecting the incidence of osteoporosis.

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    Degradation of BCR-ABL fusion protein in chronic myeloid leukemia cells induced by isoalantolactone
    Chen CHEN, Feng-hou GAO
    2021, 41 (7):  891-897. 
    doi: 10.3969/j.issn.1674-8115.2021.07.007

    Abstract ( 110 )   HTML ( 10 )   PDF (2200KB) ( 17 )  
    Objective

    ·To explore the effect of isoalantolactone (Iso) on imatinib-sensitive and drug-resistant chronic myeloid leukemia (CML) cells, and the molecular mechanism of down regulating BCR-ABL fusion protein.

    Methods

    ·K562 and K562R cells were treated with different concentrations of Iso for 0, 24, 36 and 48 h, respectively. The inhibitory effect of Iso on CML cells was determined by CCK-8 method. The apoptosis of K562 and K562R cells induced by Iso for 24 h was detected by flow cytometry. CML cells were treated with different concentration of Iso for different time, and the effect of Iso on the level of BCR-ABL fusion protein was detected by Western blotting. The effect of Iso on BCR-ABL mRNA level in CML cells was detected by reverse transcription and quantitative real-time PCR (qPCR). K562 cells were treated with proteasome inhibitor MG132, autophagy inhibitor 3-methyladenine and lysosomal inhibitor chloroquine combined with Iso, respectively, and K562 and K562R cells were treated with caspase inhibitor Z-VAD-FMK combined with Iso. The level of BCR-ABL fusion protein was detected by Western blotting. Caspase 3 (CASP3) and caspase 7 (CASP7) were knocked down in K562R cells, and their effects on the down-regulation of BCR-ABL fusion protein induced by Iso were detected.

    Results

    ·The proliferation of CML cells was inhibited by Iso in a dose- and time-dependent manner. Flow cytometry showed that Iso could increase the apoptosis of K562 and K562R cells (both P<0.05). Western blotting showed that Iso could induce the decrease of BCR-ABL fusion protein level, while qPCR showed that BCR-ABL mRNA level had no significant change. MG132, 3-methyladenine and chloroquine could not reverse the down-regulation of BCR-ABL fusion protein induced by Iso, but Z-VAD-FMK could partially reverse the down-regulation. Knockdown of CASP3 could partially reverse the degradation of BCR-ABL protein induced by Iso, while CASP7 could not.

    Conclusion

    ·Iso can target the degradation of BCR-ABL fusion protein, which provides an experimental basis for overcoming drug resistance of CML cells.

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    Clinical research
    Natural history and symptom evolution of acoustic neuroma: an analysis of 56 patients
    Jun-ji YAO, Jian-qing CHEN, Hao-yue TAN, Zhao-yan WANG, Zhi-hua ZHANG, Hao WU, Huan JIA
    2021, 41 (7):  898-902. 
    doi: 10.3969/j.issn.1674-8115.2021.07.008

    Abstract ( 113 )   HTML ( 3 )   PDF (1044KB) ( 21 )  
    Objective

    ·To preliminarily observe the natural history of the sporadic acoustic neuroma and its relationship with clinical manifestations in Chinese population.

    Methods

    ·From March 2016 to November 2019, the patients with sporadic acoustic neuroma who had visit and follow-up in the Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine were analyzed retrospectively. The patients included in the study were required to have at least two digital data of enhanced MRI, and the interval between the first and the last time was more than 60 d. Their radiological DICOM data (enhanced MRI), audiological reports (pure tone average threshold and speech discrimination score), and clinical manifestations (hearing loss, tinnitus, vertigo, and facial pain or numbness) were collected. Image data were loaded by HorosTM software to measure tumor size and calculate tumor growth rate. Then the relationship between tumor growth rate and clinical manifestations was analyzed.

    Results

    ·A total of 56 patients were included, 28 males and 28 females, with the average age of (48.6±12.0) years old. Their initial tumor size was (15.9±9.6) mm in the maximum diameter, and the mean interval between the two times of MRI was (266.3±313.5) d. The average growth rate was (4.4±4.7) mm/a. Eight cystic tumors grew more rapidly than non-cystic ones [(9.4±3.8) mm/a vs (3.6±4.4) mm/a, P=0.003). Among the 48 non-cystic acoustic neuromas, 22 internal auditory canal type and small (≤10 mm) tumors grew more slowly than other tumors [(2.1±3.6) mm/a vs (4.8±4.7) mm/a, P=0.031]; the tumors grew more slowly in the patients with the ages of 60 years or above than those in the patients younger than 60 years old [(1.7±3.1) mm/a vs (4.2±4.6) mm/a, P=0.040]. 58.8% of the patients undergoing active “wait and scan” strategy had stable tumors, and 81.8% patients with measurable hearing did not show hearing deterioration during their follow-up. Other factors like sudden deafness, tinnitus, vertigo, initial hearing level, sex, and tumor side had no correlations with tumor growth rate (all P>0.05).

    Conclusion

    ·Cystic sporadic acoustic neuroma is confirmed as a rapid growth tumor, which needs active treatment. The tumors grow slowly in the non-cystic acoustic neuromas which are internal auditory canal type, not bigger than 10 mm or in the patients aged 60 years and above. The cases that are suitable for “wait and scan” policy can basically maintain their original hearing level during one year.

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    Clinical characteristics and prognosis of pediatric acute leukemia patients with MLL gene rearrangements
    Qing LIU, Na ZHANG, Jing-bo SHAO, Hong LI, Kai CHEN, Cheng-kan DU, Zhen WANG, Hui JIANG
    2021, 41 (7):  903-909. 
    doi: 10.3969/j.issn.1674-8115.2021.07.009

    Abstract ( 205 )   HTML ( 12 )   PDF (1094KB) ( 69 )  
    Objective

    ·To analyze the clinical characteristics and prognosis of pediatric acute leukemia (AL) patients with positive mixed linage leukemia (MLL) gene rearrangement (MLL-r).

    Methods

    ·Forty-five children with MLL-r AL admitted to Shanghai Children′s Hospital, Shanghai Jiao Tong University from January 1, 2009 to December 31, 2019 were retrospectively analyzed. Fluorescence in situ hybridization and/or fluorescent real-time PCR were used to detect the MLL-r. Kaplan-Meier method was used to evaluate the survival of children. Log-rank test was used to compare the difference of survival rate. Univariate analysis and multivariate analysis were performed on the factors influencing survival, such as gender, age and the number of white blood cells.

    Results

    ·The incidence rate of MLL-r in children with AL in our center was 7.1%, and the incidence rate of MLL-r in children with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) were 5.4% and 13.3%, respectively. The difference between the two groups was statistically significant (P=0.002). The age of the two groups of children (>1 year and ≤1 year) and the number of white blood cells at the time of onset (≥50×109/L and <50×109/L) were compared. The differences were statistically significant (P=0.032 and 0.021). The main immunophenotype of children with MLL-r ALL was early precursor B-ALL, accounting for 79.2%. The main immunophenotype of children with MLL-r AML was M5, accounting for 77.8%. MLL partner gene analysis showed that MLL/AF4 accounted for 59.2% (16/27) of MLL-r ALL children, of which 68.7% (11/16) were children younger than 1 year old. Compared with the children younger than 1 year old in the non-MLL/AF4 group, the difference was statistically significant (P=0.034). The majority of children with MLL-r AML were MLL/AF9, accounting for 33.3%. Of the 45 patients, 42 cases were included for the prognosis analysis. The complete remission rate was 97.6% (41/42), and the median follow-up time was 26 (2?138) months. The median event-free survival (EFS) and overall survival (OS) time were 21 months and 24.5 months, respectively. The 3-year EFS and OS rates were (41.8±9.4) % and (60.9±9.3) %, respectively. The median duration of EFS and OS in children with MLL-r ALL were 21.5 months and 28 months, respectively, and the 3-year EFS and OS rates were (44.3±11.7) % and (58.2±12.1) %, respectively. The median EFS and OS time in children with MLL-r AML were 16 months and 23 months, respectively. The 2-year EFS and OS rates were (36.5±15.8) % and (64.7±14.5) %, respectively. Eight cases of ALL children relapsed, with a median recurrence time of 20 (2?36) months; 7 cases of AML children relapsed, with a median recurrence time of 16 (5?38) months, and the cumulative recurrence rates were 48.4% and 63.9%, respectively. There was no statistically significant difference between them (P=0.398). Univariate analysis showed that between the groups of MLL-r ALL children >1 year and ≤1 year, white blood cell count ≥50×109/L and <50×109/L, platelet count ≥30×109/L and <30×109/L, there were statistically significant differences in the EFS rate. The P values were 0.028, 0.024 and 0.027 respectively. Multivariate analysis showed that the number of white blood cells at onset was an independent prognostic factor affecting EFS in children with MLL-r ALL (RR=6.113, 95% CI 0.017?1.050, P=0.013).

    Conclusion

    ·The incidence of MLL-r in children with AML is higher than that in children with ALL. The main immunophenotype of MLL-r ALL is early precursor B-ALL. The main immunophenotype of MLL-r AML is M5. Conventional chemotherapy produces a high response rate, which is likely to relapse. The number of white blood cells at the onset ≥50×109/L is a poor prognostic factor for children with MLL-r ALL.

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    Preliminary analysis of vestibular function in patients with eosinophilic otitis media
    Yue ZHOU, Peng-jun WANG, Hui WANG, Dong-zhen YU, Zheng-nong CHEN, Ya-qin WU, Hai-bo SHI
    2021, 41 (7):  910-914. 
    doi: 10.3969/j.issn.1674-8115.2021.07.010

    Abstract ( 86 )   HTML ( 2 )   PDF (1331KB) ( 13 )  
    Objective

    ·To discuss the effect of eosinophilic otitis media (EOM) on vestibular function.

    Methods

    ·Data of 8 EOM patients (EOM group) were collected. Additionally, 16 cases of chronic suppurative otitis media (CSOM group) and 16 healthy volunteers (control group) matched with age, gender and course of disease were selected for comparison. All participants were monitored by pure-tone test, acoustic impedence, video head impulse test (vHIT), vestibular evoked muscular potential (VEMP), and dynamic posturography (DPG). And then, date of the three groups were analyzed.

    Results

    ·Compared with the control group, there was a statistically significant difference in the composition ratio of the types of hearing loss in the EOM group (P=0.000), while there was no significant difference in the composition ratio between the EOM group and the CSOM group (P=0.892). In vHIT, the gain values of semicircular canals in the EOM group were significantly different from those of the CSOM group (P=0.035), without visible difference from those of the control group (P=0.220). The gain values of upper and posterior semicircular canals in the EOM group were not significantly different from those in both the CSOM group and control group (P=0.807, P=0.971, P=0.683, P=0.610). In cVEMP and oVEMP, the abnormal rate of the EOM group was significantly higher than that of the control group (P=0.002, P=0.033), while being compared with the CSOM group, there was no significant difference (P=0.631, P=0.352). In cVEMP, the incubation periods of P1 and N1 in the EOM group were significantly longer than those in the control group (P=0.000, P=0.000) , and the amplitudes of P1-N1 in the EOM group were lower than those in the control group and CSOM group (P=0.000, P=0.000). In DPG, the composite score (P=0.025), visual score (P=0.017), vestibular score (P=0.040) and visual preference score (P=0.006) of the EOM group were significantly lower than those in the control group. And the composite score of the EOM group was also obviously lower than the CSOM group (P=0.024).

    Conclusion

    ·EOM tends to lead to more severe inner ear neurotoxicity than neutrophil-mediated infective middle ear inflammation. Since vestibular dysfunction has the characteristics of compensatory remission, patients with EOM may not have obvious symptoms of vertigo. Systematic and comprehensive assessment of vestibular function is helpful to reveal functional disability, and then targeted rehabilitation therapy can be carried out.

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    Relationship between CTRP2 and coronary collateral circulation
    Jing TANG, Chen-xi YU, Zhong-li CHEN, An-di ZHANG
    2021, 41 (7):  915-919. 
    doi: 10.3969/j.issn.1674-8115.2021.07.011

    Abstract ( 93 )   HTML ( 1 )   PDF (2022KB) ( 16 )  
    Objective

    ·To explore the relationship between C1q/tumor necrosis factor-related protein-2 (CTRP2) and collateral circulation in patients with coronary artery occlusion.

    Methods

    ·Firstly, 177 patients who were hospitalized in the Department of Cardiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from September 2019 to December 2019 and were diagnosed with coronary artery obstruction by coronary angiography were selected. According to the Rentrop method, the patients were classified into two groups: poor collateral circulation formation group and good collateral circulation formation group. ELISA was used to detect the level of adipokine complement CTRP2 in patients′ plasma. The animal model of lower limb ischemia was established and divided into contrast group and CTRP2 overexpression group. The recovery of blood supply was measured by laser Doppler instrument and the recovery ratio of blood supply was calculated. Finally, the recombinant CTRP2 protein was used to stimulate vascular endothelial cells at the doses of 50, 100 and 200 pg/mL, and the percentage was detected on Matrix Gel. The migration ability of endothelial cells was detected by Trans-well.

    Results

    ·Clinical study found that the plasma CTRP2 level in patients having coronary artery occlusion with good collateral formation was higher than that in patients with poor collateral circulation (P=0.009), and the risk ratio of CTRP2 to poor collateral circulation was OR=0.889, 95%CI 0.844?0.936, P=0.000. The animal model study found that CTRP2 can promote the recovery of blood supply in mice with lower limb ischemia (P=0.032, P=0.009). Cell experiments showed that CTRP2 enhanced the angiogenesis and migration ability of endothelial cells, and it was positively correlated with its concentration (all P<0.05).

    Conclusion

    ·The level of plasma CTRP2 in patients having coronary artery occlusion with good collateral circulation is increased. CTRP2 can promote the establishment of collateral circulation in vivo and the angiogenesis and migration of endothelial cells in vitro.

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    Application of artificial intelligence to CT diagnosis of thoracic traumatic rib sites: a preliminary study
    Xiang LIU, Hui-hui XIE, Yu-feng XU, Xiao-feng TAO, Lin LIU, Di-jia WU, Xiao-ying WANG
    2021, 41 (7):  920-925. 
    doi: 10.3969/j.issn.1674-8115.2021.07.012

    Abstract ( 142 )   HTML ( 6 )   PDF (2371KB) ( 52 )  
    Objective

    ·To assess the detection rate of an artificial intelligence (AI) software for acute traumatic rib fractures on chest computed tomograph (CT) images.

    Methods

    ·A consecutive cohort of CT images of the patients with acute chest trauma were collected from August 2019 to September 2019 (n=393). The reference standard was defined as the consensus reading results of three radiologist experts. At the lesion level, the sensitivity was studied, including all lesions and different types of rib fractures (i.e., displaced rib fractures, mild fractures, and cortical distortion). The sensitivity was also studied at both patient and rib levels.

    Results

    ·At the lesion level, the total rib fracture detection sensitivity of AI was 81.75%. For displaced rib fractures, the sensitivity was 94.85%, which was the highest among the three types of fractures (P=0.000). When all types of rib fractures were taken as the object of study, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of AI were 82.45%, 98.33%, 75.30% and 98.91% respectively at the rib level, and 90.91%, 76.21%, 77.63% and 90.23% respectively at the patient level. When displaced rib fracture were taken as the object, the sensitivity, specificity, PPV and NPV of AI were 94.57%, 98.26%, 51.94% and 99.89% respectively at the rib level, and 95.56%, 74.59%, 52.76% and 98.26% at the patient level.

    Conclusion

    ·AI software has high sensitivity in detecting the fracture sites, and it could be potentially used for screening the thorax CT images in patients with acute chest trauma.

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    Application of wearable dynamic electrocardiogram recorder to screening of atrial fibrillation
    Wen-xia FU, Li-xiu CHEN, Jia-wei LE, Ruo-gu LI
    2021, 41 (7):  926-930. 
    doi: 10.3969/j.issn.1674-8115.2021.07.013

    Abstract ( 103 )   HTML ( 1 )   PDF (906KB) ( 40 )  
    Objective

    ·To compare the performance of wearable dynamic electrocardiogram (ECG) recorder and twelve-lead ECG products, and verify the effectiveness and safety of the wearable dynamic ECG recorder in the detection of atrial fibrillation (AF).

    Methods

    ·One hundred and fourteen subjects were included and underwent ECG examination simultaneously. Subjects were placed in a supine position and upright positions before and after exercise. Wearable dynamic ECG and twelve-lead ECG were used for ECG collection. Using the twelve-lead ECG as standard, the effectiveness of AF detection results, including consistency, sensitivity, specificity, positive predictive value and negative predictive value for detection of AF, was evaluated.

    Results

    ·According to the ECG diagnosis results, the patients were divided into two groups, including 61 patients in the non-AF group and 53 patients in the AF group. The age of the AF group was significantly higher than that of the non-AF group (P=0.000); CHA2DS2-VASc score of the AF group was higher than that of the non-AF group (P=0.001). The proportion of patients with coronary heart disease in the AF group was higher than that in the non-AF group (P=0.014). There were significant differences in the proportion of oral anticoagulants, antiplatelet agents, calcium channel blockers, diuretics, digoxin, and β-blockers between the two groups (all P<0.05). The 60 s-ECG monitoring of the wearable dynamic ECG recorder was automatically determined by the artificial intelligence (AI) algorithm in a supine position: 47 cases of AF, 65 cases of non-AF, and 2 cases not determined. Compared with that of twelve-lead ECG ("unable to judge" as false positive and false negative), the diagnostic consistency of the wearable dynamic ECG recorder for AF was 94.74% (95%CI 88.76%-97.80%). The sensitivity of the wearable dynamic ECG recorder to diagnose AF was 88.68% (95%CI 77.06%-95.07%), and the specific was 100% (95%CI 92.91%-100%). The positive predictive value was 100% (95%CI 90.98%-100%), and the negative predictive value was 91.04% (95%CI 81.48%-96.16%). In an upright position, it was automatically determined by the AI algorithm: 50 AF cases, 61 non-AF cases, and 1 case not determined. Compared with that of the twelve-lead ECG ("unable to judge" as false positive and false negative), the diagnostic consistency of the wearable dynamic ECG recorder for AF was 97.37% (95%CI 92.21%-99.44%). The sensitivity of the wearable dynamic ECG recorder to diagnose AF was 94.34% (95%CI 84.03%-98.65%), and the specific was 100% (95%CI 92.91%-100%). The positive predictive value was 100% (95%CI 91.48%-100%), and the negative predictive value was 95.31% (95%CI 86.57%-98.92%). The results after exercise were the same as that of the standing position. No adverse events occurred throughout the test, and no apparent device defect was found.

    Conclusion

    ·The wearable dynamic ECG recorder has higher specificity and positive predictive value. Moreover, the operation is simple, which could increase the detection rate of paroxysmal AF.

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    Evidence-based medicine
    Meta-analysis of efficacy of transcranial magnetic stimulation for the treatment of cognitive function and behavioral and psychological symptoms of dementia in patients with Alzheimer′s disease
    Yi WANG, Cheng CHENG, Hong-yan SHEN, Hong-yan GAO, Yue-ning DAI, Zheng-hui YI
    2021, 41 (7):  931-941. 
    doi: 10.3969/j.issn.1674-8115.2021.07.014

    Abstract ( 132 )   HTML ( 0 )   PDF (4396KB) ( 26 )  
    Objective

    ·To evaluate the efficacy of transcranial magnetic stimulation (TMS) on cognitive function and behavioral and psychological of dementia (BPSD) in Alzheimers disease (AD) patients.

    Methods

    ·Nine databases including China National Knowledge Infrastructure (CNKI), WanFang, VIP, Chinese Biomedical Literature Database (CBM), PubMed, Embase, the Cochrane Library and Chinese and American Clinical Trial Center were searched before November 2, 2019. English was searched with the topics of “Alzheimers disease” “transcranial magnetic stimulation” and “randomize controlled trial”, and free words were retrieved. Chinese was searched with the topics of “阿尔茨海默病”“经颅磁刺激”“随机对照试验”. According to the pre-established inclusion and exclusion criteria, the literatures were screened. RevMan 5.3 software was used. The standardized mean difference (SMD) was used as the effect value, and 95% confidence interval (CI) was used for interval estimation. Gradeprofile 3.2.2 software was used to evaluate the quality of evidence.

    Results

    ·A total of 23 articles were included. In improving cognitive function, the evaluation results of AD Assessment Scale-Cognitive suggest that SMD of high frequency TMS group was -0.64 (95%CI -0.89 ? -0.40, P=0.000), SMD of low frequency TMS group was -0.58 (95%CI -1.12 ? -0.05, P=0.030). The Grade of evidence quality was very lower and lower respectively. When using Mini-Mental State Examination to evaluate cognitive function, it was divided into three subgroups according to TMS frequency (high or low, value) and treatment times. The results showed that SMD in high frequency TMS group was 1.30 (95% CI 0.76?1.85, P = 0.000), but no significant difference was found in low frequency group. The Grade of evidence quality were both very lower. In 5 Hz group, SMD was 3.99 (95%CI 0.81~7.16, P=0.010) and the Grade evidence quality grade was very low. In the group of treatment times >40 and ≤60, SMD was 3.28 (95%CI 1.67?4.90, P=0.000) and the Grade evidence quality grade was very low. In the aspect of improving BPSD, the Neuropsychiatric Inventory was used to evaluate, and the result was no statistically significant. The Grade evidence quality grade was very low. Behavioral Pathology in Alzheimers Disease Scale showed that SMD of high frequency group was -0.83 (95%CI -1.06? -0.60, P=0.000), and there was no significance in low frequency group.The Grade evidence quality grade were low and very low respectively.

    Conclusion

    ·TMS could improve the cognitive function of patients with AD, and high frequency was better than low frequency. The quality of evidence was lower. Whether the BPSD of AD patients were effective needs further research. In the future, more high-quality clinical multicenter randomized controlled trails should be included to study the efficacy and safety of TMS in the treatment of AD, so as to provide guidance for clinical practice.

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    Public health
    Development of self-management scale for peritoneal dialysis at home and its reliability and validity analysis
    Ze-hui HUANG, Chun HU, Pu LI, Chun-li ZHANG, Jun-yan FANG, A-hui SONG, Shan WEI, Ou-yang JI, Yan TONG, Hai DENG, Ying-li LIU
    2021, 41 (7):  942-948. 
    doi: 10.3969/j.issn.1674-8115.2021.07.015

    Abstract ( 98 )   HTML ( 2 )   PDF (941KB) ( 40 )  
    Objective

    ·To complete the compilation and reliability and validity analysis of the self-management scale for peritoneal dialysis (PD) patients during home dialysis operations.

    Methods

    ·The preparation of the initial scale was based on patient interviews, expert consultation, literature review, and clinical experience in PD patient management. Convenient sampling was used to distribute questionnaires. Critical ratio method and homogeneity test were used to screen items. With the help of exploratory factor analysis to evaluate the validity of the structure, the number of common factors and items of the scale were finally determined, and the reliability of the scale was verified by the Cronbach′s α coefficient and the half coefficient.

    Results

    ·The initial scale was composed of 26 items in 5 dimensions, and 136 questionnaires were distributed and 132 valid questionnaires were collected. According to the results of the project analysis, except item 3 that did not meet the criteria for the corrected correlation between the item and the total score, commonality, and factor loading, all the other items met the selection criteria. Since this item was a key step in investigating the patients′ awareness of sterility, this item was retained for factor analysis after expert consultation. The Kaiser-Meyer-Olkin measure of sampling adequacy (KMO) of the initial questionnaire was 0.880, and the χ2 value of Bartlett′s spherical test was 2 272.938 (P=0.000). The results suggested that the overall correlation matrix had common factors, which was suitable for factor analysis. According to the original intention of the initial design items of the scale, 5 common factors were limited and extracted, and the maximum variation method of orthogonal rotation axis was adopted, and finally items 7, 11, and 16 were deleted. According to the variable characteristics contained in each factor construct, the extracted common factors were named as “recognition of dialysis complications and adequacy evaluation” “peritoneal standardized operation” “drug management” “dietary management” and “dialysis effect evaluation and monitoring”, respectively, to form a formal questionnaire with 23 items in 5 dimensions. The eigenvalues of each dimension were 4.604, 3.286, 3.207, 2.817, and 2.140, and the cumulative variance contribution rate was 66.428%. The Cronbach′s α coefficient of the total scale was 0.930, and the half coefficient was 0.946.

    Conclusion

    ·The self-management scale for PD patients has good reliability and validity, which can be used to evaluate the self-management ability of PD patients.

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    Review
    Research progress in amino acid PET imaging of pediatric brain tumors
    Zi-hao LIU, Wen-fang TANG, Hui WANG
    2021, 41 (7):  949-952. 
    doi: 10.3969/j.issn.1674-8115.2021.07.016

    Abstract ( 107 )   HTML ( 3 )   PDF (760KB) ( 29 )  

    Brain tumor is the most common solid tumor in pediatric tumors with the highest rate of mortality. Conventional magnetic resonance imaging (MRI) indicates some limitations in diagnosis, surgical management and prognosis for pediatric brain tumors. Positron-emission tomography (PET) is an imaging technology that reflects the biological characteristics of tumors. By using the biological distribution of specific radiopharmaceuticals, PET can provide different metabolic information of the tumor and complement the morphological information of conventional MRI. Amino acid PET imaging uses the metabolism of radiolabeled amino acids in human to perform functional imaging of tumors. The benefits of amino acid PET imaging include diagnosis and grading, biopsy planning, prognosis, recurrence monitoring, and efficacy evaluation. This paper reviews the application of amino acid PET/CT and PET/MRI to pediatric brain tumors.

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    Preparation of cell membrane-coated nanoparticles and its application to antimicrobial
    Ting-wang SHI, Yun-feng CHEN
    2021, 41 (7):  953-958. 
    doi: 10.3969/j.issn.1674-8115.2021.07.017

    Abstract ( 151 )   HTML ( 1 )   PDF (1598KB) ( 86 )  

    Due to the complex pathophysiological characteristics of the infected microenvironment and the development of bacterial resistance, conventional antibiotic treatments are facing increasingly more clinical challenges. Cell membrane-coated nanoparticle (CMCNP) is a kind of biomimetic materials emerging in recent years which can be obtained by directly wrapping the membrane vesicles onto the nanoparticle cores through physical means. Recently, CMCNP has displayed a wide application prospect in the areas of targeting infected areas, neutralization of bacterial toxins and development of antibacterial vaccines with the help of biological functions of cell membrane vesicles and the superior physicochemical properties of nanoparticles. However, CMCNP is still at the experimental stage in the biomedical field, and its safety and effectiveness need to be further verified for clinical applications.

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    Application of hydrogel sustained-release system to periodontal tissue regeneration
    Tung-liang HSIA, Jia-chen DONG, Rong SHU
    2021, 41 (7):  959-962. 
    doi: 10.3969/j.issn.1674-8115.2021.07.018

    Abstract ( 107 )   HTML ( 5 )   PDF (892KB) ( 55 )  

    As an emerging functional polymer material, hydrogel has great potential for development, and is widely used in bioengineering. Because of its good biocompatibility, it has also gradually received attention in the medical field. Some studies have shown that hydrogel sustained-release system can promote the proliferation and adhesion of human periodontal ligament fibroblasts and effectively promote their differentiation into osteoblasts and cementoblasts. This paper briefly reviews the application of hydrogel to periodontal tissue regeneration.

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    Clinical research progress of Janus kinase inhibitors in the treatment of atopic dermatitis
    Hao-jun ZHUANG, Mei-liang GUO, Wan-wen LIU, Hui DENG
    2021, 41 (7):  963-966. 
    doi: 10.3969/j.issn.1674-8115.2021.07.019

    Abstract ( 130 )   HTML ( 1 )   PDF (800KB) ( 68 )  

    Atopic dermatitis is a chronic inflammatory skin disease, which is mainly related to changes in Th2 type signaling pathways. Increased expression of interleukin-4 (IL-4) and IL-13 reduces filaggrin, which leads to skin barrier defects. The Janus kinase-singal transducer and activator of transcriprion (Jak-STAT) signaling pathway is closely related to the pathogenesis of atopic dermatitis. Inhibiting the Jak-STAT signaling pathway is a potential method to treat atopic dermatitis. Janus kinase (JAK) inhibitors can be divided into first-generation and second-generation JAK inhibitors in the selection of JAKs′ inhibition. By summarizing the efficacy and safety of the first-generation and second-generation JAK inhibitors in clinical trials, the clinical research progress of JAK inhibitors in the treatment of atopic dermatitis is clarified.

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    Research progress of the role of gut microbiota in the pathogenesis and treatment of obsessive-compulsive disorder
    Ying-dan ZHANG, Zhen WANG
    2021, 41 (7):  967-971. 
    doi: 10.3969/j.issn.1674-8115.2021.07.020

    Abstract ( 137 )   HTML ( 6 )   PDF (853KB) ( 93 )  

    Obsessive-compulsive disorder (OCD) is a chronic and disabling psychiatric disorder characterized by recurrent intrusive thoughts or repetitive behaviors. However, the etiology is complex and the underlying pathophysiology remains unclear. In recent years, microbiota-gut-brain (MGB) axis has become a research hotspot in the field of psychiatry. Gut microbiota, as a key medium of the bilateral connection between brain and intestine, plays an important role in immune inflammation, neuroendocrine and brain development. This review illustrates possible link between OCD and MGB axis and the underlying etiological pathway. And treatment options targeting the gut microbiome is also further discussed.

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    Review of the factors influencing bone metabolism in schizophrenia
    Hong-yan XUAN, Li-hua WANG, Hua-fang LI
    2021, 41 (7):  972-976. 
    doi: 10.3969/j.issn.1674-8115.2021.07.021

    Abstract ( 106 )   HTML ( 3 )   PDF (833KB) ( 30 )  

    The patients with schizophrenia experience a higher rate of low bone mineral density, osteoporosis and fractures than the general population, which affects not only their quality of life but also their long-term outcomes. Previous studies have shown that there are many factors affecting individual bone metabolism, including drugs, gender, age, hypogonadism, lifestyle, etc. Combined with clinical research, this article summarizes three aspects, i.e.,the disease itself, the use of antipsychotics and the unhealthy lifestyle. This review aims to discuss the influencing factors of bone metabolism in the patients with schizophrenia, and then expound briefly on the diagnosis and intervention measures of osteoporosis, which may provide a reference for clinical prevention and intervention of osteoporosis in the patients with schizophrenia.

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    Risk factor and management strategy of premature ventricular contraction-induced cardiomyopathy in children
    Bo CHEN, Peng-jun ZHAO
    2021, 41 (7):  977-981. 
    doi: 10.3969/j.issn.1674-8115.2021.07.022

    Abstract ( 82 )   HTML ( 1 )   PDF (805KB) ( 39 )  

    Premature ventricular contraction-induced cardiomyopathy is a potentially reversible disease, and frequent premature ventricular contraction will cause left ventricular dysfunction and remodeling. Previous studies on adults and animal models have found that cardiac myocytes and extracellular mechanisms may be involved in the development of cardiac dysfunction, but the exact pathophysiological mechanism is still unclear. Moreover, there is no clear guidance for early diagnosis and intervention strategies in children. A series of adult studies have proved that a variety of high-risk factors lead to premature ventricular contraction-induced cardiomyopathy, including premature ventricular burden and ventricular premature contraction variability. However, studies on children are limited to case reports and retrospective, small-sample-size, single center series. This review summarizes and analyzes the high-risk factors of premature ventricular contraction-induced cardiomyopathy in children and the current intervention strategies.

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    Application and prospect of chimeric antigen receptor-modified T cell therapy for glioblastoma
    Paerhati NADINA, Yan YAN, Qian-ji CHE, Jing LUO, Xin-nan LIU, Bin LI
    2021, 41 (7):  982-986. 
    doi: 10.3969/j.issn.1674-8115.2021.07.023

    Abstract ( 93 )   HTML ( 1 )   PDF (861KB) ( 42 )  

    Glioblastoma is one of the most common and deadly neoplasms in adults. The rapid progress and strong invasiveness of glioblastoma and the presence of the blood-brain barrier make the treatment of glioblastoma different from other solid tumors and these are the reasons for the poor prognosis of conventional treatment. The exploration of immunotherapy in the treatment of glioblastoma has lasted for decades, but the outcome is not good yet. However, with the research progress of glioblastoma-specific antigen, the development of various related technologies and the success of early clinical trials, it has come back to people's attention. Chimeric antigen receptor-modified T cell(CAR-T) is a new kind of tumor immunotherapy. Reviewing the previous literatures, this article summarizes some related antigens that can be used to CAR-T therapy to treat glioblastoma, the problems and challenges faced by CAR-T therapy in the treatment of glioblastoma and other solid tumors, including T cell depletion in tumor microenvironment, heterogeneity of tumor and low homing rate, and some potential improvements in CAR-T therapy.

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