Table of Content

05 May 2021, Volume 41 Issue 5

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Original Articles

Expression of ID2 in lung bud organoids promotes pulmonary vascular formation

LIU Hong-xian, YANG Jun

2021, 41(5):  623-629. 

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Objective To investigate the role of inhibitor of DNA binding-2 (ID2) in pulmonary vasculature formation in early lung development. Methods CRISPR/Cas9 system was used to edit ID2 in human embryonic stem cells (hESCs) to construct ID2 knockout strains, hESCs and ID2 knockout strains were further differentiated into endothelial cells(ECs) or lung bud organoids (LBOs).Quantitative PCR was used to detect ID2, CD31, NKX2.1 and other genes expression during differentiation, flow cytometry was performed to analyze the differentiation efficiency, Western blot was applied to check ID2, CD31 and PAX9 protein expression, 3D co-culture of ECs and LBOs was performed to compare the effect of LBOs derived from different hESCs on the tubular formation of ECs. Results ID2 promoted cells to enter the mesoderm stage during the differentiation of hESCs into ECs, but ID2 deletion led to the formation of a large number of ECs with tubular defects. ID2 promoted the differentiation of hESCs into LBOs.In the 3D co-culture system, LBOs could promote ECs tube-forming ability, while the deficiency of ID2 weakened this promotion. Conclusions In early stage of pulmonary tissue development, ID2 affects the differenti- ation and function of ECs and LBOs, loss of ID2 in lung bud reduces the angiogenesis of surrounded ECs.

Translational regulation of human embryonic kidney cell line HEK293

LIU Man, REN Yue, GAO Yu-feng, WANG Fang, YU Jia

2021, 41(5):  630-635. 

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Objective To investigate the translational regulation of human embryonic kidney (HEK)293 cell line. Methods Polysome profiling coupled with Western blot was used to verify the translational activity of HEK293 cells. RPL10A and RPS17 RNA immunoprecipitation coupled with sequencing (RIP-seq) and bioinformatic analysis were used to investigate the actively translating mRNAs. Results A total of 129 genes were found in the RNA immunoprecipitation experiments RPL10A and RPS17, among which 93.8% were protein-coding genes and enriched in RNA splicing, metabolism, MAPK signal pathway, chromatin localization and RNA transport. Conclusions A variety of molecules involved in HEK293 cells translation are obtained by RPL10A and RPS17 RIP-seq analysis.

Screening of cis-acting elements for maintaining pluripotency of human embryonic stem cells

SUN Meng-yao, LIU Si-qi, ZHOU Fan-qi, MA Yan-ni, YU Jia

2021, 41(5):  636-640. 

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Objective To establish an inducible CRISPR library screening method for human embryonic stem cells (hESCs) to screen the cis-acting elements involed in the maintainance the pluripotency of hESCs. Methods The inducible Cas9 expression elements were inserted into the hESC genome to construct an inducible Cas9 stable expression strain (iCas9-hESC). Analyze the published chromatin interaction information in hESCs to identify the cis-acting elements that may be involved in the regulation of pluripotency genes, then to construct a double gRNA CRISPR knockout library. The CIRSPR library was used to infect iCas9-hESC at low multiplicity of infection followed by induction of Cas9 expression, and gene editing of the cells. Using the expression level of OCT4 as a standard to measure pluripotency, the cells after gene editing were stained with OCT4 and analyzed by flow cytometry to determine whether the knockout of cis-elements would affect the pluripotency of hESCs. Results The iCas9-hESC was successfully constructed, and the cells still maintained a pluripotent state. Construct a CRISPR knockout library of ciselements and successfully infect the target cells. Flow cytometric analysis of the expression level of OCT4 was performed on the cells after the library infection, and it was found that there were indeed some populations with decreased pluripotency in the cells after gene editing. Conclusions A feasible scheme for screening cis-acting elements involved in maintaining pluripotency in hESCs through CRISPR library is established.

PARP14 is increased in the hippocampus of three mouse depression models and its relationship with neuroinflammation

LI Chen, XIU Jian-bo, XU Qi

2021, 41(5):  641-647. 

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Objective To explore whether ADP ribose polymerase 14(PARP14) is related to depression and does it affect the inflammatory response of microglia. Methods Three kinds of mouse depression model were established to find potential relationship between the expression level of PARP14 and the change in depression-related brain areas including chronic restraint(CRS)model, chronic unpredictable mild stress(CUMS)model, lipopolysaccharide (LPS) model. Then the effect of Parp14 over-expression and knockdown on inflammatory response was examined in immortalized microglia cell line BV2. Results The expression of PARP14 increased in the hippocampal tissues of all three kinds of depression models, and the expression of PARP14 in the CRS model group was correlated with the expression level of inflammatory response factors in the tissues. The expression level of PARP14 also increased after stimulation of mouse immortalized microglia cell line BV2 by LPS .At the same time, BV2 cells with over-expression of PARP14 expressed more pro-inflammatory cytokines as a response to LPS stimulation, while those with knockdown Parp14 or treatment with PARP14 inhibitor showed the opposite results. Conclusions This study shows that the expression level of PARP14 in the hippocampus of depression model mice increased, which may enhance the level of neuroinflammation and aggravate depression-like phenotype by exacerbating the :PS induced inflammatory response of microglia cells .

Establishment and validation of a method labelling neural progenitor cells with CFSE

ZHOU Jia-feng, MA Meng-jie, PENG Xiao-zhong, SHU Peng-cheng

2021, 41(5):  648-652. 

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Objective Establishing and verifying a method for labeling neural progenitor cells (NPCs) with carboxyl fluorescein diacetate succinimidyl ester (CFSE) fluorescent probe. Methods CFSE was injected into the lateral ventricle of embryonic mice to label ventricular zone (VZ) cells. The tissue was collected at 1 and 3 hours after injection to detect its specificity by immunofluorescence. Dorsal neocortex was separated at 1 hour after injection, the strong positive cells were sorted by fluorescence activated cell sorting (FACS) and the cell identity was verified by stem cell markers and neuronal markers. Results CFSE instantaneously labelled (pulse labeling) cells in the ventricular zone, and the labeling window was between 3 and 6 hours. Signal of CFSE when performing long-term labeling would be attenuated. Seventy percent of the cells sorted by CFSE were neural precursor cells, and a small portion of which were neurons. Conclusions CFSE can be used for pulse and long-term labeling in vivo. Also, CFSE can be applied for sorting NPCs, while the current sorting strategy needs to be adjusted to improve specificity.

Application of RNA-targeted CRISPR/CasRx system in mouse spermatogonia cell line GC1-spg

LI Meng-zhen, LIU Jun, ZOU Ding-feng, MIAO Shi-ying, WANG Lin-fang, SONG Wei, LI Kai

2021, 41(5):  653-660. 

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Objective To investigate the application of CRISPR/CasRx mediated gene knockdown at the RNA level in mouse spermatogonia cell line GC1-spg. Methods The EF1a core promoter. CasRx.SV40.U6.DRs expression plasmid (CasRx-gRNA) and three fluorescent protein of EF1a.EGFP, EF1a.mCherry, EF1a.tdToamto expression plasmids were constructed by homologous recombination. Three fluorescent protein expression plasmids and CasRx-gRNA expression plasmids were transiently transfected into human embryonic kidney cell line HEK-293T, and the knockdown of exogenous gene (the fluorescent proteins,EGFP and mCherry) was used to detect by fluorescence intensity and Western blot. Additionally, the expression levels of endogenous gene (mRNA and lncRNA) were measured by q-PCR in HEK-293T cells transfected with CasRx-gRNA. The exogenous gene egfp, mCherry and CasRx-gRNA expression plasmids were transiently transfected into the mouse spermatogonia cell line GC1, and the knockdown efficiency of exogenous gene (the fluorescent proteins) was detected by the above method. Results CasRx-gRNA and three kinds of fluorescent protein expression plasmids were constructed successfully. After CRISPR/CasRx mediated RNA interference of exogenous genes (egfp, mCherry) and endogenous genes (mRNA, lncRNA) in HEK-293T cells, the expression level was significantly reduced (P＜0.01). The CRISPR/CasRx system was verified in the mouse spermatogonia cell line GC1, which could effectively and specifically knock down exogenous genes egfp and mCherry. Conclusions CRISPR/CasRx system exerts an effective and specific knock-down function in GC1-spg, providing a new gene silencing tool potentially used in the study of male reproduction.

Predictive value of Xiaoyan decoction combined with GC chemotherapy in the treatment of advanced non-small cell lung cancer based on DWI

HAN Yan, GUAN Bing-qi, ZHOU Gang, MA Fei

2021, 41(5):  661-666. 

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Objective To explore the predictive value for the efficacy of Xiaoyan decoction combined with gemcitabine/carboplatin (GC) chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC). Methods The clinical data from 65 patients with advanced NSCLC who were treated with Xiaoyan decoction and GC chemotherapy were analyzed retrospectively. The apparent diffusion coefficient before and after treatment (ADC_pre and ADC_post) of magnetic resonance diffusion-weighted imaging (DWI) and ADC change rate (ΔADC) were compared between the effective group and the ineffective group. The correlation of ADC_pre and ADC_post and ΔADC with tumor regression rate and their predictive value for curative effect were analyzed. Results The effective rate of Xiaoyan decoction combined with GC chemotherapy was 58.46%. Before treatment, DWI showed a high signal, ADC_pre was low, and DWI was mainly equal signal and ADC_post was high after treatment. The tumor regression rate was negatively correlated with ADC_pre, and positively correlated with ADC_post and ΔADC(P＜0.05). The sensitivity, specificity, accuracy and AUC of ADC_pre for efficacy prediction were 71.05%, 81.48%,75.38%, 0.789, respectively, and ADC_post was 89.47%, 66.67%, 80.00%, 0.810, and ΔADC was 81.58%, 85.19%, 83.08%, 0.842. Conclusions ADC_pre, ADC_post and ΔADC are closely related to tumor regression rate in advanced NSCLC patients. DWI can predict the clinical efficacy of Xiaoyan decoction combined with GC chemotherapy.

Analysis of survival prognosis of degree of surgical treatment with targeted therapy for 224 cases of intermediate- and high- risk gastrointestinal stromal tumors patients

CUI Yi, HAN Zhen-guo

2021, 41(5):  667-673. 

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Objective To explore the degree of radical surgery for patients with intermediate- and high-risk gastrointestinal stromal tumors (GIST) and to find the correlation between targeted drug therapy and survival prognosis, and then to summarize the clinical diagnosis and treatment experience. Methods A retrospective reciew of the complete pathological and follow-up data of intermediate and high risk GIST patients diagnosed by surgery and pathology in Shanxi Bethune Hospital from September 2012 to December 2019 was made, and the relevant factors that affect their prognosis. Results The patient's gender, age, tumor location, whether it was ruptured, the degree of radical surgery was summarized, targeted therapy, and the overall survival (OS) of 3 and 5 years were different(P＜0.05). The location of the primary tumor in GIST patients, whether the tumor was ruptured, the degree of radical surgery, and targeted therapy were independent prognostic factors that affected their 3-year and 5-year OS. There were differences in the prognosis of patients with different degrees of radical surgery, different risk grades, and whether to use targeted drug therapy(P＜0.05). Conclusions Complete surgical resection (R0) combined with targeted therapy is the main treatment to improve the prognosis of patients with intermediate- and high-risk GIST, but patients with intermediate-risk GIST who received targeted drug therapy after surgery are failed to significantly improve their overall survival.

Orexin A promotes glutamate uptake and inhibits delayed neuronal death in hippocampus CA1 region of transient global cerebral ischemic rats

ZHOU Hong, DENG Jian, YANG Feng, YU Jie, HU Lin-wang

2021, 41(5):  674-679. 

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Objective To investigate the effect and mechanism of orexin-A(OX-A) on the expression and function of glial glutamate transporter-1(GLT-1) and delayed neuronal death (DND) in hippocampus CA1 region of transient global cerebral ischemia(tGCI) in rats. Methods The rats were randomized into sham group, model group, OX-A group and OX-A+LY294002 group. The binding and glutamate uptake of GLT-1 in hippocampal CA1 region were detected by the [³H]-glutamate labeling method. The content of glutamate in hippocampal CA1 region was determined by the glutamate quantitative kit. The pathological changes of neurons in hippocampal CA1 region were observed by Nissol, NeuN and Fluro-Jade C staining. The expressions of GLT-1, p-PI3K and p-Akt in hippocampal CA1 region were detected by Western blot. Results OX-A promoted the binding and glutamate uptake of GLT-1, increased glutamate content, GLT-1 expression and PI3K/AKT signaling activity, and inhibited DND in the hippocampal CA1 region of tGCI rats (P＜0.05); However, LY294002 attenuated the above therapeutic effects of OX-A(P＜0.05). Conclusions OX-A can increase the expression and function of GLT-1 and reduce DND in the hippocampal CA1 region of tGCI rats by enhancing the activity of I3K/AKT signal.

Gene knockdown of angiopoietin-like protein 3 reduces the occurrence and development of thoracic aortic aneurysms

YU Hua-hui, JIAO Xiao-lu, YANG Yun-yun, LI Fan, SUN Qiu-ju, YU Yu, LYU Qian-wen, QIN Yan-wen

2021, 41(5):  680-687. 

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Objective To explore the role of angiopoietin-like protein 3 (ANGPTL3) in the development of thoracic aortic aneurysm (TAA) and its possible mechanism. Methods The TAA patients who underwent open surgical repair in Beijing Anzhen Hospital were selected as the experimental group (n=6), and the aortic tissue in the control group was obtained from a heart transplant donor (n=6). Another 30 3-week-old male C57BL/6J mice were randomly divided into control (control) and β-aminopropionitrile (BAPN)-induced TAA model groups (n=15 per group). The aortic tissue was taken 4 weeks later. Immunohistochemical method was used to detect the expression of ANGPTL3 in human thoracic aortic aneurysm tissue, immunohistochemistry were used to detect the expression of ANGPTL3, IL-6, MMP2, and MMP9 in mouse aortic tissue, and TUNEL method was used to detect apoptosis. Immunofluorescence co-localization was used to detect the localization of ANGPTL3 in vascular tissues. Transfect human aortic smooth muscle cells with ANGPTL3 siRNA. Observe the effect of ANGPTL3 knockdown on AngⅡ-induced smooth muscle cell apoptosis and inflammatory response. Results In the aortic tissues of patients with thoracic aortic aneurysm and TAA mice, the expression of ANGPTL3 protein increased significantly (P＜0.05), vascular smooth muscle cell apoptosis, and the protein expressions of inflammatory factors IL-1β, MMP2, and MMP9 were all significantly increased(P＜0.05). In addition, ANGPTL3 knockdown can significantly reduce AngⅡ-induced smooth muscle cell apoptosis and inflammatory factor secretion (P＜0.05). Conclusions The ANGPTL3 protein level is increased in the development of thoracic aortic aneurysm. Inhibition of ANGPTL3 protein expression can reduce the cell apoptosis and inflammation of smooth muscle cells. It suggests that targeting ANGPTL3 may inhibit the development of thoracic aortic aneurysms by inhibiting cell apoptosis and inflammation in smooth muscle.

Influence of splicing factor MBNL3 on malignant biology behavior of pancreatic cancer cells

HAO Wen-zhen, CHEN Jie-min, FENG Yun-lu, WU Xi, WANG Qiang, WU Dong, YANG Ai-ming

2021, 41(5):  688-693. 

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Objective To investigate MBNL3 expression and its effect on malignant biology behavior of pancreatic cancer cells. Methods Fifty paraffin samples of pancreas cancer excised during surgery in Peking Union Medical College Hospital from 2017 to 2020 were collected. Immunohistochemistry was conducted to explore expression of MBNL3. Pancreatic cancer cells were treated with MBNL3 knocked down or over-expressed by transfection. The proliferation and invasion or migration in different pancreas cells were examined respectively by real time cellular analysis and Transwell assay. The colony formation in different pancreas cells were examined by plate colony forming test. The MBNL3 expression in cell lines was analyzed by Western blot. Results Overall staining score of MBNL3 in pancreatic cancer tissues was 5.0±2.7, significantly higher than that of adjacent tissues(2.1±0.6)(P＜0.05). Cell proliferation experiment showed that 72 h after transfection, MBNL3 knockdown groups grew slower than control group in pancreatic cancer cells, whereas MBNL3 over-expressed groups grew faster than control group. Transwell assay showed that 10 h after transfection, invasion and migration of MBNL3 knockdown groups were weaker than control groups in pancreatic cancer cells (P＜0.05),meanwhile MBNL3 over-expressed groups were stronger than control groups in pancreaticcancer cells (P＜0.05). Colony forming experiments showed that colony formation number of MBNL3 knockdown groups were less than control groups in pancreatic cancer cells (P＜0.05), and the same of MBNL3 over-expressed groups were more than control group in pancreatic cancer cells(P＜0.05). Conclusions MBNL3 is highly expressed in pancreatic cancer tissue, which might take part in regulating the proliferation, invasion and migration of pancreatic cancer cells.

Distribution of MTHFR and MTRR polymorphisms in Han and Buyi women at Libo county of Guizhou province

QIN Yi-wang, MO Mei-xiang, ZHANG Long-jiong, LUO Yin-ya, WEI Liang-yin, HU Ji-fang, LU Yan-qiang

2021, 41(5):  694-697. 

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Objective To conduct molecular epidemiological investigations on Han and Buyi women at Libo county of Guizhou province aiming for the identification of genetic polymorphisms coding the key enzymes for folate metabolism MTHFR and MTRR. Methods A total of 1 342 healthy women who received perinatal health care at the People's Hospital of Libo county were recruited, including 236 Han people and 1 106 Buyi people. Oral mucosal epithelial exfoliated cells were collected for genomic DNA extraction, MTHFR C677T, A1298C, and MTRR A66G gene polymorphisms were examined with quantitative PCR for statistical analysis. Results 1)The genetic polymorphism distribution of the subjects was in line with genetic balance. 2)The genotype frequency of MTHFR 677CC, CT, and TT of Han women was 49.6%, 39.8%, and 10.6% respectively,and that of Buyi women were 61.8%,33.7% and 4.4%. The frequencies were 62.3%, 33.1%, 4.7%, and Buyi females were 47.4%, 42.9%, and 9.7%, both points are significantly different(P＜0.05). The genotype frequencies of MTRR 66AA, AG, and GG of Han women were 56.4%, 37.4%, and 5.9%, respectively, and that of Buyi women were 57.0%, 36.0%, and 7.1%, with no difference. 3)Han and Buyi women MTHFR C677T and A1 298C had 6 combinations of two-point linkage without CT/CC, TT/AC and TT/CC. The highest frequency of Han women was CT/AA, and the highest frequency of Buyi women was CC/AC. The haplotype constructed by the two loci had three combinations of CA, TA, and CC, and there was a complete linkage disequilibrium between the two loci. Conclusions The genetic characterization of MTHFR and MTRR polymorphisms in Han and Buyi women at Libo county provides a basis for guiding folic acid supplementation and implementation of personalized pregnancy health care.

Effect of miR-183 targeting Bnip3l on mitochondrial autophagy in hypoxia/reoxygenated hippocampal neurons in mice

MA Jia-ling, GAO Yan-ping

2021, 41(5):  698-703. 

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Objective To explore the mechanism of miR-183 regulating mitochondrial autophagy in hypoxia/reoxygenated(H/R) hippocampal neurons. Methods The mouse hippocampal neuron HT-22 cells were collected and divided into control group, hypoxia/reoxygenation(H/R) model group (HR group), miR-183 over-expression group (miR-183 mimics group), and negative control group (miR-183 NC group). The anoxia and reoxygenation models were established by the method of anoxia 3 h+reoxygenation for 12 h, miR-183 mimics group and miR-183 NC group were transfected with miR-183 mimics and miR-183 NC on the basis of HR group. The survival rate of HT-22 cells was measured by MTT method, the ultra structure of mitochondria was microscopied and the levels of miR-183 and mitochondrial autophagy related genes Bnip3l mRNA were detected by RT-qPCR; Western blot was used to detect the expression of autophagy related proteins Bnip3l, beclin-1, ubiquitin and LC3 binding protein p62 (p62), microtubule related protein light chain 3 (LC3-Ⅱ)/LC3-Ⅰ. The targeting relationship between miR-183 and Bnip3l was verified by double Luciferase Report. Results Compared with control group, the autophagy of membrane structure in HT-22 cells increased in HR group and miR-183nc group, and melanin remained after autophagy, cell survival rate, miR-183 and p62 protein expression were all decreased (P＜0.05), the expression of Bnip3l mRNA and protein, beclin-1 and microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ)/LC3-Ⅰ proteins all increased(P＜0.05); In the miR-183 mimics group, except for the reduced cell survival rate, all the above indicators were opposite to the HR group with statistical significance (P＜0.05). Compared with miR-183 NC+ Bnip3l-3′UTR-WT group, the activity of luciferase in miR-183 mimics + Bnip3l-3′UTR-WT group decreased(P＜0.05). Conclusions The over-expression of miR-183 can target at inhibiting the expression of Bnip3l mRNA, the mitochondrial autophagy of HT-22 cells, and thus aggravate the damage of HT-22 cells caused by H/R.

Proanthocyanidins inhibit the secretion of Aβ_1-42 induced by Aβ_25-35 in human neuroblastoma cell line SH-SY5Y

LI Qi, ZHANG Xiao-qiang, TAO Yi-fan, ZHU Meng-wen, CUI Dan-dan, SUN Teng-teng

2021, 41(5):  704-708. 

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Objective To investigate the effect of proanthocyanidins(PC) induced by amyloid-beta peptide(Aβ_25-35) in human neuroblastoma cell line SH-SY5Y and its possible mechanism. Methods SH-SY5Y cells were exposed to Aβ_25-35 to establish a cell injury model in vitro. PC and(or) secretory protein Dickkopf-1 (Dkk1), the endogenic inhibitor of Wnt/β-catenin signaling pathway were used for intervention. The cells were divided into control group, Aβ_25-35 group, PC(different concentrations)+Aβ_25-35 groups, Dkk1 group, Dkk1+ PC+Aβ_25-35 group.The cell viability was evaluated by MTT assay. The expressions of β-catenin, GSK-3β, p-GSK-3β were measured by Western blot. The secreted Aβ_1-42 was detected by ELISA. Results Compared with the control group, the cell viability, the expression of β-catenin and p-GSK-3β were reduced in Aβ_25-35 treated group(P＜0.05), while the secreted Aβ_1-42 was increased (P＜0.05). PC improved the cell viability, increased the expression of β-catenin and p-GSK-3β, and reduced the secreted Aβ_1-42 in SH-SY5Y cells induced by Aβ_25-35 (P＜0.05). After using Dkk1,the ability of PC was decreased on the enhancement of β-catenin expression, the improvement of p-GSK-3β expression, and the reduction of the secreted Aβ_1-42 (P＜0.05). Conclusions PC may decrease Aβ_1-42 secretion in SH-SY5Y cells induced by Aβ_25-35 through Wnt/β-catenin signaling pathway.

A cohort-based case control study on the association between the whole blood iron and copper with cardiovascular diseases

HUANG Xian, WU Shou-ling, CHEN Shuo-hua, SUN Yuan-yuan, ZHANG Di, GUO Shu-xia, WANG Li

2021, 41(5):  709-714. 

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Objective To investigate the association between whole blood iron, copper and their interaction with cardiovascular diseases (CVD). Methods A cohort-based case control study was conducted. Cases were 93 males with CVD in the Kailuan cohort who participated in the follow-up in 3 hospitals in 2017-2018. During the same period, 372 males with non-CVD who were 1∶4 individual matched by age and labor type were selected as controls. The concentration of blood iron and copper was determined by inductively coupled plasma mass spectrometry. Conditional logistic regression models were used to estimate the association between blood iron and copper and CVD, respectively and elastic-Net regression models to estimates interaction between the two metals and CVD. Results The whole blood iron concentration in the cases was significantly higher than the controls, while blood copper concentration was lower than the controls (both P＜0.001). After adjusting for age, smoking, drinking, overweight, hypertension, diabetes, anemia, hyperlipidemia, and high sensitivity C-reactive protein, the participants with higher iron increase 3.17 times (OR=4.17, 95% CI: 2.23-7.79, P＜0.001) risk of CVD than those with lower iron, and those with lower copper increase 3.26 times (OR=4.26, 95% CI: 1.73-10.45, P＜0.01) risk than those with the higher copper. Adaptive Elastic-net regression analysis showed that it under the simultaneous exposure of higher iron and lower copper, the risk of CVD with environment risk score ＞0.232 was 8.96 times (OR=8.96, 95% CI: 4.47-17.95, P＜0.001) than the score ≤0.232. Conclusions Higher iron and copper deficiency may be independent risk factors for CVD. Environment risk score could be a good indicator of simultaneous exposure of blood iron and copper, which should have a better predictive value of CVD.

Resveratrol promotes the polarization of rat microglial cell line to M2 type with oxygen glucose deprivation/reoxygenation via up-regulating the expression of annexin A1

LIN Min, ZHANG Hong-mei

2021, 41(5):  715-720. 

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Objective To explore the role of annexin A1 (ANXA1) in resveratrol regulation of M2 type polarization of rat microglial cell line with oxygen glucose deprivation/reoxygenation (OGD/R) model. Methods Lentivirus LV-shAnxA1 was used to silence the expression of AnxA1 in N9 cells. LV-Scramble acted as a control lentivirus. Western blot and RT-qPCR were used to verify the efficiency of lentivirus infection. 3 d after lentivirus infection, the N9 cell OGD/R model was constructed. 3 days after reoxygenation, the cells were treated with resveratrol for 24 hours. The groups were as follows: OGD/R(-) group, OGD/R(+) group, OGD/R(+)+Res group, OGD/R(+)+Res+LV-Scramble group, OGD/R(+)+Res+LV-shAnxA1. RT-qPCR and Western blot were used to detect the mRNA and/or protein content of ANXA1, CD11b, tumor necrosis factor (TNF-α), Interleukin-1β(IL-1β), arginase-1 (Arg-1) and Interleukin-10 (IL-10). Immunofluorescence was applied to observe the distribution of ANXA1 in cells. Results The level of ANXA1 mRNA and protein in OGD/R(+)+Res group was significantly higher than that in OGD/R(+) group. The ANXA1 protein in the OGD/R(+) group was mainly distributed in the nucleus,while the ANXA1 protein in the OGD/R(+)+Res group was mainly distributed in cytoplasm. After inhibiting the expression of ANXA1, the OGD/R(+)+Res+LV-shAnxA1 group ANXA1 was mainly located in the nucleus. Compared with the OGD/R(+)+Res group, the CD11b protein content in the OGD/R(+)+Res+LV-shAnxA1 group was significantly increased (P＜0.01), and the TNF-α and IL-1β mRNA levels were significantly increased(P＜0.001), while Arg-1 and IL-10 mRNA levels were significantly reduced. Conclusions Resveratrol promotes the polarization of rat microglial cell line wih OGD/R model to M2 type via upregulation of ANXA1 expression.

Clinical Sciences

Effects of different anesthesia methods on postoperative sleep quality in elderly patients with hip fracture

SONG Ya-nan, YUAN Yi, ZHANG Wen-chao, WANG Geng, LI Zheng-qian, GUO Xiang-yang

2021, 41(5):  721-725. 

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Objective To compare the effect of spinal anesthesia and general anesthesia(GA) on postoperative sleep quality in elderly patients undergoing hip surgery. Methods In this prospective cohort-based study, patients with hip fracture, aged ≥65 years were divided into 2 groups according to the anesthesia method: combined spinal plus epidural anesthesia(CSEA) group and GA group(n=69 each) from November 2019 to August 2020. All patients received the same perioperative pain management. Subjective sleep quality was assessed by the sleep diaries recording sleep quality, total sleep time, and number of awakenings. The Objective sleep quality was assessed by sleep tracker recording total sleep time(TST), rapid-eye-movement(REM) time, light sleep time and deep sleep time. Numeric Rating Scales(NRS) were used to assess the intensity of postoperative pain. Results Compared with CSEA group, the Sleep Quality Score and deep sleep time were significant lower(P＜0.05), and the number of awakenings(P＜0.05) was significant higher in GA group in the intraday night of surgery. Conclusions Compared with CSEA group, sleep disruption is more severe in the GA group at the intraday night of the patients with hip fracture.

Evaluation of fiberoptic ductoscopy in diagnosis and treatment of pathological nipple discharge

ZHANG Lu, LI Zhi, SHI Li-hui

2021, 41(5):  726-728. 

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Objective To explore the clinical value of fiberoptic ductoscopy in the diagnosis and treatment of pathological nipple discharge. Methods A total of 313 patients with pathological nipple discharge from October 2018 to June 2019 in the Breast Surgery Department of Tongzhou Maternal ＆ Child Health Hospital, Beijing were retrospectively reviewed. Results Fiberoptic ductoscopy was performed in 313 patients with pathological nipple discharge, 124 cases were space occupying lesions and underwent surgical operation. Postoperative pathology confirmed 6 cases of ductal carcinoma in situ, 1 case of lobular carcinoma in situ, 5 cases of atypical hyperplasia, 5 cases of intraductal papillomatosis, 6 cases of multiple intraductal papilloma, 38 cases of intraductal papilloma, 4 cases of fibroadenoma, 9 cases of breast adenosis and 50 cases of hyperplasia of mammary glands. Conclusions Fiberoptic ductoscopy can directly diagnose the etiology of pathological nipple discharge. The guide wire localization surgery guided by fiberoptic ductoscopy can more accurately remove the intraductal lesions, and fiberoptic ductoscopy can detect early breast cancer by nipple discharge.

Technology and Methodology

Comparison of two acquisition modes in urine metabolomics by untargeted mass spectrometry

XIAO Xiao-lian, LIU Xiao-yan, ZHU Wen-feng, YANG Ye-hong, YANG Jun-tao, SUN Wei

2021, 41(5):  729-734. 

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Objective To compare the advantages and disadvantages of full scan acquisition (FSA) mode and data dependent acquisition (DDA) mode for untargeted metabolomic analysis. Methods Qualitative and quantitative results of two acquisition methods were compared by using a standard mixture of 9 metabolites and human urine sample. Results In the analysis of standard sample, the metabolite abundance in FSA mode was about 2.36 times higher than that in DDA mode (P＜0.05), the CV of metabolites abundance ranged from 2.14% to 11.20% in DDA mode and from 0.81% to 6.35% in FSA mode. In the analysis of urine sample, there was no statistical difference in the number of spectra and metabolite feature between FSA mode and DDA mode. When injecting 1, 2 and 4 μL, the number of metabolites identified by FSA mode was 9.5％, 1.9％ and 10％ higher than those identified by DDA mode, respectively. And the median CV of metabolite abundance analyzed by FSA(7.1％,3.0％ and 2.6％)was significantly lower than that by DDA(10.3％, 7.0% and 6.5%). When injecting 1, 2 and 4 μL,with the increase of abundance, the median CV of metabolite abundance in DDA mode was 1.3-1.7,1.7-1.8 and 1.4-1.9 times higher than that in FSA mode (P＜0.05), and with the increase of peak width, the median CV of DDA mode was 1.5-1.8, 1.7-2.1 and 2.0-2.2 times higher than that of FSA mode (P＜0.05). Conclusions FSA mode requires high system stability, it is suitable for fast and small-scale sample analysis; DDA mode has lower requirement for system stability, and is convenient and time-saving, which can be used for long-time and large-scale sample analysis.

Analysis of Difficult Cases

Two-case reports of alveolar adenoma

WAN Meng-yao, BING Zhong-xing, ZHANG Jia-qi, ZHOU Liang-rui, CHEN Ye-ye, HUANG Cheng, ZHANG Ye, LI Shan-qing

2021, 41(5):  735-738. 

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From August 2010 to August 2020, there were 3 cases of pathologically diagnosed alveolar adenoma (AA) were reported in Peking Union Medical College Hospital so far, which was a rare benign neoplasm of the lung. The clinical manifestations and radiological characteristics on computer tomography of AA were heterogenous among these patients and lacked specificities. The difficulty in predictive differentiation of benign or malignant characteristic of the lesion led to some confusions in clinical practices. This paper reported 2 cases of AA and reviewed the literature of AA. Its clinical, radiographical and pathological characters were analyzed, so to provide more knowledge and improve the differential diagnosis of this disease.

Mini Reviews

Hydrogen sulfide attenuates diabetic cardiomyopathy by inhibiting oxidative stress

JIAO Li-jie, WEI Ya-xin, LI Hong-zhu

2021, 41(5):  739-743. 

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Although there are a variety of pathological mechanisms attributed to diabetic cardiomyopathy (DCM), oxidative stress is one of the most important causes of DCM. Understanding the occurrence and development of oxidative stress in DCM is very important for the new targeted therapy of DCM. In addition, hydrogen sulfide (H₂S) plays an important role in the treatment of various cardiovascular diseases. In particular, H₂S can reduce DCM by inhibiting oxidative stress through various pathways.

Research progress on the role of ADAM17 in the pathogenesis of atherosclerosis

TANG Bai-yi, WEN Juan, TANG Xiao-hong

2021, 41(5):  744-748. 

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Atherosclerosis is a kind of chronic inflammatory disease involving imbalance of lipid metabolism and immune disorders. The disintegrin metalloprotease 17(ADAM17) is a classic membrane protein shedding enzyme, which promotes atherosclerosis by participating in the process of inflammatory response, angiogenesis and plaque instability. In a few cases, ADAM17 also exhibits anti-atherosclerotic effects. Therefore, paying attention to the mechanism of ADAM17 in atherosclerosis will help to provide new insights into the diagnosis and treatment of atherosclerosis.

Research progress on post-transcriptional dysregulation of mRNA in pathogenesis of Alzheimer's disease

SUN Jing-yao, TONG Wei-min, NIU Ya-mei

2021, 41(5):  749-752. 

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Post-transcriptional regulation of mRNA is an essential step from RNA transcription to gene translation, the process includes mRNA splicing, nuclear export, translation, and decay. Post-transcriptional dysregulation in the brain is one of the causal factors of Alzheimer's disease. This review summarizes the dysfunctional post-transcriptional regulation of APP, MAPT and many other risk genes of AD identified so far. Meanwhile, RNA N⁶-methyladenosine methylation is the most abundant epitranscriptomic mark on mRNA and regulate almost every step in mRNA metabolism. Due to the abnormal expression of m⁶A regulators and participation in alternative splicing of risk genes in AD, the hypothesis proposes that post-transcriptional dys-regulation mediated by m⁶A may function as a novel pathogenic factor of AD .

Research progress of acidic nucleoplasmic DNA-binding protein 1

CUI Ya-ting, GOU Wen-feng, WEI Hui-qiang, YU Jiang, HOU Wen-bin, LI Yi-liang

2021, 41(5):  753-757. 

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Acidic nucleoplasmic DNA-binding protein 1 (And-1/WDHD1) as a natural chimerical protein, is characterized by containing the WD-repeat and the HMG-box motif families. And-1 is over-expressed in multiple tumors and involved in the whole cell cycle containing prereplication complex (Pre-RC) assembly, DNA replication, checkpoint activation, DNA repair and sister chromatid cohesion establishment. As a novel target for cell cycle regulation, And-1 can be used in the development of broad-spectrum anti-cancer drugs. This article focuses on the research on the structural characteristics, biochemical functions and potential roles of And-1 in cancer in recent years, in order to provide references for the further research of And-1 and the development of new drugs.

Medical Education

Preliminary practice and evaluation of Harvard Medical School's Training to Teachers China Program

ZHAO Jun, SHI Yue, CHENG Xi, FENG Yun-ying, LIU Ji-hai

2021, 41(5):  758-762. 

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Objective To explore the practical effect of Harvard Medical School's T2T (Training-to-Teachers) Program for young clinical teachers and to improve the construction of medical discipline teaching echelon. Methods Twenty-six teachers from Peking Union Medical College Hospital were selected to participate in the T2T Program. The project consisted of medical education module of online courses, webinar, online test, capstone project, and workshop. At the end of the project, the feedback results of real-name questionnaires of all participating teachers were used to evaluate the practical effect of T2T Program. Results All the teachers undertook certain teaching tasks. Program members gave a high appraisal to the whole program: more than 90% of the members agreed that they had learnt the advanced medical education concept (96.2%), curriculum design method (96.1%), the practical teaching methods and teaching evaluation strategy(96.1%),and most of them agreed that they had learnt the practical design method for teaching and scientific research (69.3%) and that the content of the course arrangement was reasonable (65.3%). Among all the program curricula, members considered that the offline workshop (73.1%) and capstone project (69.2%) were the most fruitful parts. After the end of the program, all teachers intended to improve the current teaching situation based on what they had learned. 80.8% of the teachers would try new practical teaching methods, and 65.4% of the teachers would write teaching articles based on the content of the program. Conclusions In general, the T2T Program has achieved its goal, which is of great guiding significance for the establishment of a new medical education talent training system in China and the improvement of teaching quality.

Application of multi-centered multi-disciplinary treatment team(mMDT) teaching model in clinical training of oncology

LI Yi-ze, KONG Sheng-nan, WANG Xiao-wen, BAI Yin-miao, JI Hong-chen, ZHANG Hong-mei

2021, 41(5):  763-766. 

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The quality of traditional sMDT(single-centered multi-disciplinary treatment team) teaching model will be affected by the centerlocation, leve of heathcare service, performance habits, dominant disciplines, and superior technologies, which will directly affect the depth and breadth of students' knowledge learning. Based on the traditional sMDT teaching, the new multi-centered MDT (mMDT) teaching model establishes cooperative teaching relationships with multiple hospitals and disciplines, cocultivates undergraduate and graduate students, and regularly conducts mMDT teaching, which effectively avoids the defects of the traditional sMDT teaching model and meets the needs of students at different levels. Through the mMDT teaching mode, students can learn the advanced clinical reasoning and techniques in different disciplines or hospitals, have a deeper understanding of the concept of comprehensive diagnosis and treatment of tumors, and improve the comprehensive quality of clinical research.

Evaluation of scientific impact for clinical supervisors based on Factor Analysis

CHANG Xing, JIA Xue-yan, ZHU Dong-wei, LUO Lin-zhi

2021, 41(5):  767-771. 

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Objective To establish an evaluation model of scientific impact of supervisors and provide reference for the construction of supervisor team. Methods Based on the literature review, a series of evaluation index were selected; and 62 supervisors for doctor degree from a well-known hospital in China were selected.Their academic conditions were evaluated by Factor Analysis. Results The evaluation of supervisors' scientific impact mainly determined by three common factors including research output factor, research input factor and academic publication factor. The total variance contribution rate of three factors reached 75.25%.There were significant differences in the scientific impact of supervisor. Totally, superisors' research input was greater than their research output. Conclusions Factor Analysis can be used to construct the evaluation model of supervisor's scientific impact. At the same time, it is of great significance to evaluate the scientific impact of supervisor for the selection of high-level mentors and the construction of supervisor team.

Teaching evaluation of online course of Traditional Chinese Medicine (TCM) for undergraduates of Nursing College, Peking Union Medical College in 2020

YANG Dan, WU Qun-li, LIANG Xiao-chun, TIAN Guo-qing, SUN Hua, PIAO Yuan-lin, ZHANG Meng-ren

2021, 41(5):  772-775. 

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Objective To evaluate the online teaching of Traditional Chinese Medicine(TCM) for undergraduates in Nursing College of Peking Union Medical College in 2020. Methods Totally 144 students were asked to fill in the questionnaire of TCM teaching focusing on 7 parts of questions:the TCM and the courses, comparison of online with offline one, the evaluation of students' autonomous learning, the comprehensive evaluation of teaching, the evaluation of learning outcomes, and the evaluation of examination The overall evaluation of the course and the evaluation of the future application of TCM were statistically analyzed. Results Totally 144 questionnaires were collected. About 90% of the students were interested in TCM and was necessary to learn. There are 76.39% of the students thought that the teaching platform of Tencent conference was the best. In online teaching, 34.72% of the students fully joined the lectures, and the others only joined part of the course. Results also showed that 48.61% of students believed the learning outcome of online teaching was similar to that of offline teaching and 22.22% preferred online one. More than 99% of the students thought that teachers had mastered the skills of using online teaching platform, and the evaluation of quality and effect of teaching was good. Over half of students (66.67%) hoped to introduce MOOC, 45.83% hoped to introduce micro class,38.89% students hoped to use flipped classroom and 55.56% of them chose open book examination combined with usual attendance for final assessment. The results also showed that 39.58% of students thought that TCM was difficult to learn and 46.93% thought that TCM could not be self-taught. More than 50% of the students said that they would let their patients receive TCM treatment or nursing in the future. Conclusions It is necessary for undergraduates in hospital of Western Medicine to study TCM and to increase the teaching hours. Online teaching raises higher standards for teachers, and the evaluation can improve teaching quality.

Journal Clubs may contribute to improve clinical research at the hospitals located in Western China

WANG Yi, CAO Xu, MA Xin-chun, ZHANG Ying, MA Yan-yan

2021, 41(5):  776-778. 

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There was a gap between the level of clinical performance /research in Western China and that in Eastern China. Through the investigation and comparison of the staff composition, beds number and research publication in the Department of Otolaryngology of two affiliated hospitals of Western and Eastern medical colleges in 2020, the weakness and barriers of medical personnel in Western China were found out. The regular Journal Clubs(JCs) is an effective method which may stimulate the interest of faculty at hospital in clinical research, enhance research level and arouse the enthusiasm of paper publication with extensive view of latest medical progress and improve the quality of healthcare service.