Table of Content

05 August 2021, Volume 41 Issue 8

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Original Articles

5-Aza-cdR improves learning capacity and memory through enhancing NR2B phosphorylation level in hippocampus of mice

LIU Xiao-lei, WANG Qiang, ZHANG Xiao-lu, SHAO Guo, JIANG Shu-yuan

2021, 41(8):  1091-1096. 

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Objective To study the effects of 5-Aza-2′-deoxycytidine (5-Aza-CdR) on learning and memory capacity of mice by step-down test and tyrosine phosphorylation of NR2B 1472 site (p-Y1472 NR2B) in hippocampus. Methods Mice were randomly divided into control group (control) and 5-Aza-CdR treatment group (5-Aza-CdR). In the test, 5-Aza-CdR (10 μmol/L) was administered to treatment group mice via intracerebroventricular injection. The ability of learning and memory in mice was evaluated by step-down test. The mRNA level of NR2B in hippocampal tissues of mice was measured by real-time PCR. NR2B and p-Y1472 NR2B in hippocampal tissues of mice were measured by Western blot and immunofluorescence. Results In the 5-Aza-CdR treatment group, the latency period was increased, the error records were decreased, the behavioral memory was significantly improved in step-down test(P＜0.05). While the expression of NR2B mRNA and protein in the hippocampus of mice was not significantly changed, the phosphorylation of p-Y1472 NR2B was increased(P＜0.05), and CDK5 activity was decreased(P＜0.05). There was no difference in NR2B fluorescence intensity between CA1 region and CA3 region, while p-Y1472 NR2B in CA1 region was significantly increased (P＜0.05). Conclusions The effects of 5-Aza-CdR on behavioral memory ability may be related to the p-Y1472 NR2B in the hippocampus of mice.

MK-801 changes the expression of mBDNF and proBDNF in the hippocampus of rats with corticosterone-induced depression-like behavior

LI Jian-guo, WANG Ying, LI Yue-tian, YAN Zi, ZHAO Xin, ZHANG Yu

2021, 41(8):  1097-1102. 

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Objective N-methyl-D-aspartate (NMDA) receptor antagonist produces antidepressant effects through the brain-derived neurotrophic factor (BDNF). However, the mechanism of NMDA regulation of BDNF expression by receptor antagonist is unclear. Methods Corticosterone (CORT) was orally administrated to induce depressive-like behaviors in rats. Using elevated plus maze test, sucrose preference test, open field test, and forced swimming test to observe the depressive-like behaviors. Western blot was applied to analyze the expression of mature BDNF (mBDNF) and precursor (proBDNF) in the dorsal and ventral hippocampus dentate gyrus (DG). Results Chronic administration of CORT induced depressive-like behaviors in rats. Acute administration of NMDA receptor antagonist dizocilpine (MK-801) alleviated the depressive-like behaviors (P＜0.05). MK-801 increased the expression of mBDNF and decreased the expression of proBDNF in the dorsal and ventral hippocampus DG of rats(P＜0.05). Furthermore, administration of deacetylases antagonist suberoylanilide hydroxamic acid (SAHA) increased the mBDNF expression, decreased the proBDNF expression, and alleviated depressive-like behaviors in CORT-treated rats (P＜0.05). However, SAHA treatment after MK-801 showed no significant changes in the expression of mBDNF and proBDNF in the hippocampus DG of CORT-treated rats. Conclusions MK-801 can change the expression of mBDNF and proBDNF in the hippocampus DG through histone acetylation to play antidepressant effects, which suggest a potential target for antidepressant therapy.

Kaempferol alleviates oxidative stress injury of human keratinocytes

ZOU Xue-lian, HU Wen, LEI Zi-xian, WANG Hong-juan, XU Chen, Halina HAIRUOLA, KANG Xiao-jing

2021, 41(8):  1103-1108. 

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Objective To explore the antioxidant effect and mechanism of kaempferol(KP), a component of Vernonia anthelmintica (L.) Willd., in human immortalized keratinocytes (HaCaT). Methods Using selective reaction/multiple response monitoring technique for quantitative analysis of the flavonoids in the seeds of Vernonia anthelmintica (L.) Willd.. HaCaT cells were divided into control group, model group(HaCaT cells were treated with AAPH to establish the oxidative stress model), low-, middle- and high-dose KP intervention groups.CCK-8 assay for proliferation, RT-qPCR was used for checking the expression of Nrf2, HO-1, NQO1, GCLC and GCLM mRNA, Western blot was used for checking the expression of Nrf2 protein. Results 1)The content of total flavonoids of Vernonia anthelmintica (L.) Willd.. was 0.97 g/100 g, and a total of 36 flavonoid compounds were quantified, the content of KP was 62.96 ng/100 g. 2)The optimum concentration of AAPH for constructing oxidative stress model was 25 mmol/L, and when the concentration of KP was 0-40 μmol/L, no obvious cytotoxicity was found. 3)Low-dose KP increased the expression of Nrf2, HO-1 and GCLC mRNA. Among them, the expression of HO-1 changed most significantly. 4)KP increased the expression of Nrf2 protein in a concentration-dependent manner. Conclusions A component of Vernonia anthelmintica (L.) Willd., reduces the oxidative stress injury of human keratinocytes, the mechanism might be related to the up-regulation of Nrf2 expression.

Pravastatin activates the anti-apoptotic signaling pathway of MAPK in pre-eclampsia mice

WANG Fu-rong, YAN Jin, HE Feng-jie

2021, 41(8):  1109-1113. 

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Objective To investigate the effect of Pravastatin on the pro-survival/anti-apoptotic pathway in placental tissue of Pre-eclampsia (PE) mice. Methods ICR mice with 8 days of gestation were randomly divided into: control group (Con) without any intervention; PE model group (PE) injected with adenovirus carrying sFlt-1 fragment (Adv-sFlt-1) via tail vein; Treatment group (PE+Pravastatin) was given Pravastatin (Pravastatin, 5 mg/(kg·d), since the 9th day of gestation. On the 19th day, heart blood and placenta were collected then serum sFlt-1 level was measured by ELISA method. Western blot was used to measure activating transcription factor-2 (ATF-2), extracellular regulated protein kinases (ERK) 1/2, heat shock protein (HSP) 27, p38 MAPK, signal transducer and activator of transcription (STAT) 3 and phosphorylation of p53 protein in the placental tissue. Results The serum sFlt-1 level of the PE model group was (95.73±8.44)ng/mL,which was significantly higher than that of the control group (55.32±5.66)ng/mL, and the phosphorylation level of ATF-2,p38, ERK, HSP27 and STAT3 protein in the placenta tissue was significantly lower than that of the control group (P＜0.05). After pravastatin treatment, the concentration of sFlt-1 decreased significantly, and the phosphorylation level of ATF-2, p38, ERK, HSP27 and STAT3 protein in the placenta tissue increased significantly(P＜0.05). Conclusions The therapeutic effect of Pravastatin on PE is related to the pro-survival/anti-apoptotic pathway that activates the MAPK pathway.

Poly (lactic-co-glycolic acid)-poly (ethylene glycol) scaffold incorporating angiopoietin 1 loaded nanoparticles promotes cardiac repair after myocardial infarction in rats

FANG Tao, YANG Wan-xi, LI Xin, CONG Zhi-cheng, ZHANG Pei-zong, QI Quan, SONG Bing

2021, 41(8):  1114-1120. 

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Objective To investigate the effect of PLGA-PEG scaffold incorporating angiopoietin 1(Ang1) loaded nanoparticle that was injected into the infarcted area of rat heart to protect the heart from infarction and explore potential mechanisms. Methods Rat models of myocardial infarction were replicated,and one week later SD rats were randomly divided into 3 groups:Ang1-PLGA-PEG injection group [injected with 100 μL nanoparticle suspension, about (1.61±0.05)μg Ang1](n=9),Ang1 injection group[injected with PBS solution of angiopoietin1(100 μL, 25 ng/μL)](n=8),the model control group(injected with 100 μL PBS solution)(n=8). Four weeks after injection,cardiac function was examined by echocardiography,scar tissue hyperplasia was measured by Masson staining, cardiomyocyte apoptosis and angiogenesis were detected by immunofluorescence. Results In comparison with other two groups,Ang1-PLGA-PEG injection group showed an increased blood vessel density in the infarcted area and maturity(P＜0.05),which prevented cardiomyocyte apoptosis (P＜0.05) The area of myocardial infarction was significantly decreased(P＜0.05), the remodeling of cardiomyopathy was reduced and these changes improved cardiac function (P＜0.05). Compared with the model control group, pure Ang1 injected into the surrounding area did not show curative effect (P＜0.05). Conclusions Injection of Ang1-PLGA-PEG nanoparticles into the infarcted area of left ventricle may promote vascular proliferation and facilitate the survival of cardiomyocytes,It provides an experimental basis for clinical application.

Wnt-5a/JNK is involved in PM2.5-induced expression of IL-6 and TNF-α of human bronchial epithelial cell line 16HBE

ZOU Wei-feng, WANG Xiao-qian, SHENG Qing, ZHU Tao, ZHOU Xiao-ting

2021, 41(8):  1121-1126. 

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Objective To explore whether PM2.5 induces the secretion of IL-6 and TNF-α in 16HBE via the Wnt-5a/JNK signaling pathway. Methods The research was implemented by rats and 16HBE cells. Rats were divided into control group and motor vehicle exhaust(MVE) group(concentration 1.5 mg/m²,2 h/day); 16HBE cells were divided into control group,PM2.5(20 μg/mL)group,control siRNA+PM2.5 group,Wnt-5a siRNA+PM2.5 group,Wnt-5a siRNA+control group,JNK inhibitor SP600125+PM2.5 group and SP600125+control group. The expressions of p-JNK and p-c-Jun in lung tissues were examined by immune-histochemistry method. The expressions of Wnt-5a,JNK,c-Jun,p-JNK and p-c-Jun were measured by Western blot. The secretions of IL-6 and TNF-α were assessed by ELISA. Results Compared with the control rat group, MVE group exhibited significantly up-regulated the expression of p-JNK and p-c-Jun(P＜0.05); Compared with the 16HBE cell control group,PM2.5 group significantly up-regulated the expressions of Wnt-5a,p-JNK and p-c-Jun and the secretions of IL-6 and TNF-α(P＜0.05);Compared with the PM2.5 group, Wnt-5a siRNA+PM2.5 group blocked these effects(P＜0.05). Furthermore,SP600125+PM2.5 group showed a significantly decreased expression of p-c-Jun and the secretion of IL-6 and TNF-α by 16HBE cells(P＜0.05). Conclusions PM2.5 induces the secretions of IL-6 and TNF-α by 16HBE cells via Wnt-5a/JNK signaling pathway.

Up-regulation of miR-433 expression inhibits proliferation of colorectal cancer cell line in vitro

ZHANG Jian, ZHANG Tong, WANG Hong-wei, ZHANG Ji-hong, ZHANG Bao-zhen, DONG Xin-min

2021, 41(8):  1127-1132. 

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Objective To study the expression and function of miR-433 in the development of colorectal cancer. Methods RT-qPCR was used to detect the expression of miR-433 in clinical specimens and serum of patients with colorectal cancer, and compared with those from adjacent tissues or at different stages of tumore development and from normal persons. The colorectal cancer cell lines HT-29, HCT-116, SW480 and normal colon cell line NCM460 were cultured, and the expression of miR-433 was measured by real-time quantitative PCR. Subsequently, miR-433 mimic was transfected into SW480 cells,CCK-8 was used to detect cell proliferation, flow cytometry was used to detect cell cycle changes, scratch test and Transwell test were used to detect cell migration and invasion respectively. Results Compared with the adjacent tissues, the expression of miR-433 in colorectal cancer tissues was significantly decreased(P＜0.05). The serum level of miR-433 in patients with colon cancer was also significantly lower than that in normal persons(P＜0.05). In addition, from stage Ⅰ to stage Ⅳ of TNM, the expression of miR-433 in colorectal cancer tissues gradually and significantly decreased. Compared with normal human colon epithelial cell line NCM460, the expression of miR-433 was down-regulated in colorectal cancer cell lines HT-29, HCT-116 and SW480(P＜0.05). Compared with the control group, the proliferation of SW480 cells was significantly inhibited(P＜0.05) and the proportion of G2 and M phase cells increased after SW480 transfection. The invasion and migration of cells decreased significantly after up-regulation of miR-433(P＜0.05). Conclusions The expression of miR-433 is decreased in colorectal cancer. Up-regulation of its expression in SW480 cells inhibits cell proliferation, invasion and migration.

Correlation of serum miR-181b and miR-27a expression with the severity of carotid atherosclerosis

ZHANG Chuan-xi, ZHANG Yu, GUO Sha-sha, LI Jing, YUAN Yi-qiang, WANG Ming-jie

2021, 41(8):  1133-1138. 

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Objective To identify the relationship between expression of serum microRNA (miR)-181b, miR-27a and the severity of carotid atherosclerosis (CAS). Methods Totally 102 patients with dyslipidemia were selected and 100 healthy people as controls.RT-qPCR was used to detect the expression of serum miR-181b and miR-27a. The expression of miR-181b and miR-27a of patients with dyslipidemia was compared with that of the control group. The influencing factors of the occurrence of CAS in patients with dyslipidemia and the correlation between serum miR-181b, miR-27a levels and the degree of CAS lesions were investigated. Results The relative expression of miR-181b in dyslipidemia patients was lower than that of the control group, while the relative expression of miR-27a was higher than that of the control group (P＜0.05). The expression of miR-181b in the cirrhosis group was lower than that in the non-cirrhotic group, and the relative expression of miR-27a, hs-CRP, LDL-C levels, and the proportion of hypertension were higher than those in the non-cirrhotic group (P＜0.05). Logistic regression analysis showed that the above indicators were independent factors influencing the occurrence of CAS in patients with dyslipidemia(P＜0.05). ROC showed that the sensitivity of relative expression of miR-181b and miR-27a in serum was 84.75% and 81.36% in the predicting the occurrence of CAS in patients with dyslipidemia, the specificity was 76.74% and 74.42%, and the accuracy was 81.37% and 78.43%, respectively, AUC was 0.791, 0.750 respectively. Pearson correlation analysis showed that the relative expression of serum miR-181b was negatively correlated with Crouse score(P＜0.05), and the relative expression of miR-27a was positively correlated with Crouse score(P＜ 0.05). Conclusions The expression of miR-181b and miR-27a in serum is abnormal in patients with dyslipidemia, and both of them are independent influencing factors of CAS, and their expression level is positively related to the severity of the disease.

Histone acetylation is decreased in X-ray radiation-induced injury of rat myocardial cell line H9c2

MENG Ying, ZHANG Zheng-yi, ZHAO Yuan, LU Chang-hong, SHANG Bo, SUN Peng-fei, ZHANG De-kui

2021, 41(8):  1139-1143. 

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Objective To investigate the effects of X-ray radiation on H9c2 cells and histone acetylation patterns, and to analyze the correlation between them. Methods H9c2 cells were randomly divided into control group and different model groups. The cells of model groups were irradiated with different doses of 2,4,6,8 Gy of X-ray radiation respectively. The activity of LDH in supernatants, the activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA) in cells were detected by chromatometry. Cell apoptotic ratio was measured by annexin V-FITC/PI staining and flow cytometry analysis. Apoptosis-related protein Bcl-2,caspase-3 and histone acetylation related protein H3K9ac,HDAC3 were detected by Western blot. Results Compared with control group, the relative activity of LDH in supernatants and relative content of malondialdehyde (MDA) in H9c2 cells were increased (P＜0.05) in model groups, the relative activity of intracellular superoxide dismutase (SOD) was decreased(P＜0.05) in model groups. The apoptotic rate of H9c2 cells was increased in model groups compared with control group(P＜0.05). The protein expression of caspase-3 increased (P＜0.05), the expression of Bcl-2 decreased in model groups(P＜0.05), and also found that the protein expression of H3K9ac significantly decreased and the expression of HDAC3 significantly increased in model groups(P＜0.05). Conclusions X-ray radiation can induce H9c2 cells' injury and apoptosis,accompanied by the decrease of intracellular histone acetylation level, this change may be related to the increase of HDAC3 expression.

Ursolic acid combined with HDAC2 inhibitor inhibits proliferation of human hepatoma cell line HepG2

TANG Jia-feng, HE Xue-lian, XIA Jing, XIONG Wei, LI Xiao-shan

2021, 41(8):  1144-1150. 

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Objective To investigate the effect of ursolic acid (UA) combined with HDAC2 inhibitor (SA) on the growth and proliferation of human hepatocarcinoma cell line HepG2 and its potential mechanism. Methods CCK-8, optical microscopy, cell clone formation and flow cytometry were used to evaluate the inhibitory effects of UA and SA on HepG2 cells after UA and SA monotherapy or combination therapy. Western blot was used to analyze the expression of HDAC2, AC-α-tubulin CDK2, CDK1, Bax, Bcl-2, and cleaved-PARP in the HepG2 cells after the treatment. Results UA had a significant inhibitory effect on the growth of HepG2 with a concentration and time-dependent manner (P＜0.01); UA inhibited HepG2 cell cloning, and the inhibitory effect was more significant when combined with SA (P＜0.01). UA combined with SA blocked HepG2 cell cycle at G₁ phase (P＜0.01); HDAC2 was highly expressed in human hepatoma SMMC-7721, HepG2, and PLC5 cell lines, and UA combined with SA significantly down-regulated HDAC2, Bcl-2, CDK2 and cyclin E1 protein expression, while up-regulated the expression of AC-α-tubulin, Bax and cleaved-PARP. Conclusions The combined application of UA and SA has a synergistic inhibitory effect on the proliferation of HepG2 cells.

Mechanical ventilation relieves sublingual microcirculation and improves right heart function in patients with high altitude pulmonary edema

SHI Jian-guo, XIAN Wen, CHEN Xiang-gui, CHEN Jun, FU Chang-huai, SONG Guang-lan

2021, 41(8):  1151-1155. 

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Objective To explore the effect of mechanical ventilation on sublingual microcirculation and right heart function in patients with high altitude pulmonary edema (HAPE). Methods Thirty HAPE patients were randomly divided into HAPE group(conventional treatment) with 14 cases and MV group (mechanical ventilation treatment) with 16 cases, 20 healthy volunteers who did not develop HAPE were randomly selected as the control group. We performed tests including the total of perfused vessel density (TVD), perfused vessel density (PVD), proportion of perfused vessels (PPV) and microcirculation flow index (MFI), left and right diameter of right atrium, anteroposterior diameter of right ventricle, internal diameter of main pulmonary artery, pulmonary artery systolic pressure, blood gas analysis in HAPE group before-after treatment, after healing and in control group. At the same time, the lung rales, lung shadow disappearance time, and clinical cure time were observed in the MV group and HAPE group. Results Compared with the control group, the pH value of the MV group and the HAPE group increased before treatment; blood oxygen saturation (SaO₂) decreased; carbon dioxide partial pressure (PaCO₂) decreased; blood lactic acid (Lac) increased (P＜0.01). Compared with the HAPE group, the MV group relieved hypoxemia, respiratory alkalosis and reduced blood lactic acid more quickly after 2 h or 6 h treatment(P＜0.05 or P＜0.01). Compared with the control group, the TVD, PVD, PPV and MFI values of the MV group and the HAPE group were significantly lower than those before treatment (P＜0.01). The TVD, PVD, PPV and MFI values of the MV group increased after 24 h treatment, which were better than those of the HAPE group (P＜0.05). Compared with the control group, the left and right atrium diameters of the MV and HAPE groups increased before treatment, the anteroposterior diameter of the right ventricle, the inner diameter of the main pulmonary artery, and the pulmonary artery systolic pressure all significantly increased (P＜0.01). After treatment, the left and right diameters of the right atrium, the anteroposterior diameter of the right ventricle, the internal diameter of the main pulmonary artery, and the systolic pressure of the pulmonary artery all decreased in MV group and HAPE group. After 24-hour treatment, MV group was better than the HAPE group (P＜0.05). Compared with HAPE group, the MV group did shorten the disappearance time of lung rales and shadows, and the clinical cure time (P＜0.01). Conclusions Mechanical ventilation may quickly relieve hypoxemia, significantly improve microcirculation disorders and right heart failure, thereby shorten hospitalization of patients with HAPE.

TLK2 promotes the proliferation, migration and invasion of human breast cancer cell lines

XIONG Yu-yuan, CHEN De-jie, MENG Lin, YAN Shan

2021, 41(8):  1156-1162. 

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Objective To explore the effects of TLK2 in breast cancer (BC) cells and its possible mechanism. Methods Immunohistochemistry and Western blot were used to detect the expression of TLK2 in BC tissues and cell lines. RT-qPCR was employed to detect the expression of TLK2 mRNA and miR-622 in BC tissues and cell lines. CCK-8, BrdU and Transwell assays were used to detect the effects of TLK2 over-expression plasmid and miR-622 inhibitors on the proliferation, migration and invasion of HCC70 cells. The targeted regulatory relationship between miR-622 and TLK2 was predicted and verified by Target scanning online analysis database and dual-luciferase reporter gene, respectively. Results The expression of TLK2 in BC tissues or cell lines was significantly up-regulated (P＜0.05), and TLK2 significantly promoted the proliferation, migration and invasion of HCC70 cells (P＜0.01). The possible mechanism suggested that miR-622 can bind to the 3′UTR of TLK2. Conclusions TLK2 is involved in promoting the proliferation, migration and invasion of BC cells, and is negatively regulated by miR-622.

Zerumbone inhibits the proliferation, migration and invasion of human non-small cell lung cancer cell line A549 through up-regulating FBXW7 expression

WAN Xue-qiong, CHEN Jia, HE Chao, YE Xing-ming

2021, 41(8):  1163-1168. 

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Objective To explore the effect of zerumbone on proliferation, migration and invasion of non-small cell lung cancer cell line and underline mechanism. Methods Human non-small cell lung cancer cells line A549 was divided into control group, zingerone-low dose group, zingerone-medium dose group, zingerone-high dose group, pcDNA group, pcDNA-FBXW7 group, and zingerone-high dose group +si-NC group, zingerone-high dose +si-FBXW7 group. Cell proliferation inhibition was detected by methyl thiazolyl tetrazolium (MTT) method, cell migration and invasion were detected by Transwell assays, and the expression of F-box with 7 tandem WD40 (FBXW7) mRNA and protein were detected by Western blot and real-time(RT-qPCR). Results Compared with control group, the proliferation, migration and invasion of A549 cells in the zingerone-low, medium and high dose groups were significantly reduced (P＜0.05), the expression of FBXW7 mRNA and protein were significantly increased (P＜0.05). Compared with the pcDNA group, the proliferation, migration and invasion of A549 cells in the pcDNA-FBXW7 group were significantly reduced (P＜0.05). Compared with the Zingerone-high-dose+si-NC group, the cell proliferation, migration and invasion ability of A549 in the Zingerone-high-dose+si-FBXW7 group was significantly increased (P＜0.05). Conclusions Zerumbone reduces proliferation, migration and invasion of non-small cell lung cancer cells, and the underlying mechanism is related to the up-regulation of FBXW7 expression.

Clinical Sciences

Motoric cognitive risk syndrome increases the risk of hospitalization in the elderly

YUAN Jing-lin, ZHAO Rui-xue, LI Xiao-dong, JIANG Xiao-yan, WANG Xiao-feng, ZHOU Xiao-mei, LI Shu-juan

2021, 41(8):  1169-1173. 

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Objective To explore the epidemiological characteristics of motoric cognitive risk syndrome (MCR) in Chinese elderly and its relationship with hospitalization. Methods Data were collected from a subcohort of the rugao longevity and aging study. Subjective memory complaints were assessed by the geriatric depression scale (GDS-15), and slow gait was assessed by the time up and go test (TUGT). MCR was determined by the presence of both. The incidence of hospitalization was recorded from the baseline survey in 2014 to the second 3-year follow-up in 2017, and the incidence of MCR in the hospitalized and non-hospitalized groups was compared to analyze the association between MCR and hospitalization. Results In this study, 1 076 subjects were enrolled, with an average age of 75.0±3.8 years old; The prevalence of MCR was 3.3%. During the 3-year follow-up period, 61.1% of the MCR group had records of hospitalization, while only 41.9% of the non-MCR group had the record of hospitalization (P＜0.05). The hospitalized group had a higher average age, and a higher proportion of men, non-illiterates, and those with hypertension, diabetes, and cerebrovascular disease. Hospital combination and the proportion of MCR is 4.8%, the hospital group was 2.3% (P＜0.05). After adjusting for age, sex, occupation, level of education, marital status, smoking status, BMI, blood pressure, diabetes and coronary heart disease, cerebrovascular disease, and other confounding factors, MCR is associated with increased risk of hospitalization in the elderly (P＜0.05). Conclusions The incidence of hospitalization was higher in the population of male especiall those with hypertension, diabetes and cerebrovascular history, MCR is significantly associated with hospitalization.

Clinical observation of COVID-19 treated with fibronectin(FN) inhalation

LIU Xu-zhi, WU Li-gang, ZHANG Shi-yang, ZHAO Wei-ming, WANG Bin, WANG Hao-qing

2021, 41(8):  1174-1176. 

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Objective To observe the clinical effect of COVID-19 treated with fibronectin inhalation. Methods Forty-eight COVID-19 patients in Department of Neurology, Xiehe Hospital,Tongji Medical College,Wuhan Huazhong University of Science and Technology,were treated with aerosol inhalation of fibronectin skin antibacterial liquid,respectively. Aerosol inhalation of fibronectin for 7-14 days was given twice a day,about 15 mL of aerosol solution each time. The duration of aerosol administration was 10-15 minutes. Results After inhalation of fibronectin for 7-14 days,the patients were given atomization twice a day,and each time the atomization liquid was about 15 mL,the clinical manifestations of patients showed that dyspnea improved,cough reduction,sputum reduction,pulmonary exudate reduction,sputum smooth and CT imaging lesions decreased. Conclusions Inhalation of fibronectin is effective for the treatment of COVID-19 infection.

Analysis of metabolism associated risk factors of hypocitrateuria in patients with kidney stone

QIAO Yi, XIAO He, FAN Xiao-hong, SHI Bing-bing, JI Zhi-gang

2021, 41(8):  1177-1180. 

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Objective To retrospectively analyze metabolism associated risk factors of hypocitrateuria in kidney stone patients. Methods Totally 92 kidney stone patients with qualified data from metabolic evaluation database of Peking Union Medical College Hospital from May 2020 to January 2021 were included in this retrospective analysis . With hypocitrateuria as dependent variable, and gender, age and metabolic factors, including body mass index, hypertension, diabetes mellitus, hyperlipidemia and hyperuricemia, as independent variables,binary Logistic regression was used to analyze metabolism associated risk factors of hypocitraturia. Results In kidney stone patients, hypertension was risk factors of hypocitrateuria (OR=4.48,95% CI:1.58～12.70,P＜0.05), and other factors were not found to be associated with hypocitrateuria. Conclusions In kidney stone patients, hypertension is a risk factor of hypocitrateuria.

Technology and Methodology

Establishment of a serum-free culture method for human amnion mesenchymal stem cells

LIU Xiao-yu, SHI Ping, PAN Bo-chen, PANG Xi-ning

2021, 41(8):  1181-1185. 

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Objective To establish a method of serum free culture for human amnion mesenthymal stem cells. Methods The hAMSCs were isolated by trypsin-collagenase two step digestion method, then cultured in serum free medium. Then immunofluorescence and WST assay were used to detect cell phenotype and cells growth. Cell migration of hAMSCs cultured in serum free medium was examined by scratch wound closure assay. The expression of growth factor was detected by real time PCR assay. Results The hAMSCs cultured in serum free medium exhibited spindle-shape characteristics, were positive for CD73, CD90, but negative for CD45 and CD34. The cell proliferation showed a U-shaped curve and the average doubling time of was 72 hours.The scratch wound closure assay demonstrated a statistically significant increase of migration as compared with those cultured in FBS.The expression of VEGF,KGF,PDGF,IGF-1 was up-regulated compared with those cultured in FBS. Conclusions A serum free culture method of hAMSCs is established, which provides an experimental evidence supporting potential application.

Mini Reviews

Research progress of HIF-1 mediated autophagy in cardiac diseases

ZHANG Liu-jie, LI Jing, WU Bo

2021, 41(8):  1186-1189. 

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Hypoxia-inducible factor 1 (HIF-1) regulates the expression of target genes to keep the balance between oxygen supply and oxygen consumption, maintains oxygen homeostasis. HIF-1 regulates autophagy in the cardiovascular system, which involves the HIF target gene BNIP3.

Progress on the role of cardiac-specific microRNA in myocardial infarction

WANG Qiang-li, ZHAO Yue, GUO Hai-dong, WANG Ying

2021, 41(8):  1190-1194. 

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Cardiac-specific miRNAs, such as miR-1, miR-133, miR499 and miR208, are widely involved in cardiogenesis, physiology and pathology of heart. Cardiac-specific miRNAs are not only involved in cardiomyocyte differentiation in early cardiogenic stages and cardiomyocyte proliferation in the late cardiogenic stages, but also in cell damage or protection, fibrosis, and ventricular remodeling in myocardial infarction (MI) after birth. Meanwhile, cardiac-specific miRNAs can mobilize bone marrow stem cells into the peripheral blood, and promote heart repair and regeneration. In addition, circulating level of cardiac-specific miRNAs are significantly elevated after MI, which makes them to be a promising diagnostic marker for early diagnosis of acute MI.

Research progress of interstitial fluid flowing along vascular wall

KONG Yi-ya, YU Xiao-bin, MA Chao, YIN Ya-jun, LI Hong-yi

2021, 41(8):  1195-1199. 

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This review mainly includes the following contents: 1) The multilevel of spatial topological structure of the fluid flow pathway is viewed from the transverse perspective (cross section), including perivascular space, basement membranes, tunica adventitia and perivascular connective tissue. And the diverse phenomenon of fluid flow at all levels of vascular structure is discussed; 2) The interstitial fluid flow in vascular trees throughout the whole body is viewed from the longitudinal perspective;3) The similarities and differences between domestic and foreign research results are compared;4) The potential physiological function of the interstitial fluid flow along the circulatory system is prospected.

Research progress of autophagy regulated by mTOR in diabetic complications

QIAN Zi-bing, LIU Jing, ZENG Pei-yun, ZHANG Qi

2021, 41(8):  1200-1204. 

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In the state of diabetes, dysfunctional autophagy may lead to pathological changes of multiple organs. The mTOR-mediated autophagy is involved in the regulation of diabetic complications and concomitant diseases, such as diabetic nephropathy, non-alcoholic fatty liver, diabetic heart disease, diabetic retinopathy, diabetic peripheral neuropathy and so on. The study on the mechanism of diabetic autophagy will help to find new therapeutic targets and better methods to prevent and treat diabetic complications.

Research progress on the role of STAT in the pathogenesis of dermatosis

ZHOU Qiong-yan, LIN Wei, XU Su-ling, ZHAO Ke-yu

2021, 41(8):  1205-1209. 

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Signal transducer and activator of transcription (STAT) proteins with transcriptional activity, which are involved in the pathogenesis and formation of skin lesions of atopic dermatitis, psoriasis, skin tumors and other dermatosis, and are related to the severity of dermatosis. Different STAT has different pathways in dermatosis. STAT regulate cell signal transduction, affect the expression of downstream factors, and exert biological effects. Further study of STAT expression level and targeted genes to explore the relationship between STAT and dermatosis will help to find potential therapeutic targets for dermatosis.

Progress of immune checkpoint inhibitors for the treatment of myelodysplastic syndrome

ZHANG Ruo-xi, HAN Bing

2021, 41(8):  1210-1215. 

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Immune checkpoint inhibitor(ICI) is a potential treatment for MDS by inhibiting the escape of tumor cells and enhancing immune responses. This article reviewed the efficacy and adverse events of clinical trials focusing on PD-1/PD-L1 and CTLA-4 inhibitors on MDS patients. Although the efficacy of single-agent ICI therapy was limited, it may have a synergistic effect with hypomethylation agent (HMA), which could be a choice for patients who fail to respond to HMA treatment. Immune-related adverse events(irAE) were observed, but most can be reversed by steroids.

Medical Education

Application of diversified teaching mode in teaching of ultrasound technology

ZHANG Yi-xiu, WANG Ya-hong, YANG Meng, ZHANG Qing, ZHU Qing-li, LYU Ke, LI Jian-chu

2021, 41(8):  1216-1219. 

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In order to improve the teaching quality and the clinical comprehensive quality of residents' training for graduates, clinical postdoctors participating in the standardized training, Department of Ultrasound has designed seven training teaching modules, including basic level courses, advanced level courses, ultrasonography operation, morning course for ultrasound residents, etc. Teachers try new methods boldly in the teaching process, so the teaching mode is constantly updated. Students actively participate in the teaching process with more extensive interaction with teachers. The teaching process is rich and effective. The application of diversified teaching mode can improve the practical skill and theoretical level of the trainees in ultrasound medicine.

Application of hierarchical and advanced training mode in standardized training of residents in ultrasound specialty

WANG Ya-hong, ZHANG Li, WANG Ying, ZHANG Yi-xiu, WU Xi-ning, GAO Lu-ying, TAO Xi-xi, LI Jian-chu

2021, 41(8):  1220-1223. 

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Objective To explore the hierarchical and advanced training mode applied in the standardized residency training to improve the quality of the program in ultrasound specialty. Methods Stratified training was conducted for ultrasound residents with different educational backgrounds, advanced training programs were developed according to grade and training stage design, and a hierarchical and advanced training system for residents training in ultrasound specialty was established, which was applied to the 2016 class of residents. The quality of ultrasonic reports of 2013 class residents before the reform and 2016 class residents after the reform was compared to evaluate the effect of the teaching reform. Results After the implementation of the hierarchical and advanced training program, the pathological coincidence rate reported by the 2016 class residents was 97.2%, while that reported by the 2013 class residents before the reform was 92.8%. The pathological coincidence rate of ultrasonic reports in the grade after the teaching reform was significantly higher than that before (P＜0.05). Conclusions The hierarchical and advanced training mode improves the training quality of ultrasound residents and can be applied in the standardized training of residents in ultrasound specialty.

Effects of WeChat-based medical popular science on anxiety and depression of hemodialysis patients during the COVID-19 pandemic

CHEN Gang, HAN Jian-fang, ZHOU Yang-zhong, SONG Dan, XIA Jing-hua, QIN Yan, CHEN Li-meng, LI Xue-mei

2021, 41(8):  1224-1230. 

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Objective To evaluate the impact of WeChat-based medical popular science on the mitigation of anxiety and depression in hemodialysis patients during the COVID-19 pandemic. Methods One hundred and eleven cases of hemodialysis patients from Peking Union Medical College Hospital in April 2020 were recruited. After obtaining the baseline demographic data and psychological evaluation, patients were divided patients into self-reading group and WeChat group. A daily education of popular science of COVID-19 was introduced for the WeChat group. After 14 days, psychological evaluation was repeated to compare the anxiety and depression scores before and after inter- vention. Results One hundred and six valid questionnaires were obtained including 29 in the self-reading group and 77 in the WeChat group. Besides average age (higher in self-reading group, P＜0.05), there was no significant difference in dialysis vintage, occupation, education level and marital status between the two groups. After the intervention of WeChat science popularization, the scores of anxiety and depression of patients were significantly lower than before (P＜0.001), and the percentage of patients without anxiety increased significantly (P＜0.05); the depression score of the self-reading group was also higher than before (P＜0.01), but the anxiety score did not decrease. The patients' baseline depression scores is positively correlated with the dialysis vintage (P＜0.05). Conclusions Medical science popularization reduces thes anxiety and depression in hemodialysis patients; doctors-motivated science popularization can improve patients' anxiety more effectively than encouraging patients to check information of their own.

Application of head-simulator in the training of dental prosthodontics for residents

DONG Hai-tao, ZHAO Ji-zhi, WAN Kuo, WU Xiao-min, ZHANG Yu, XIA Tian, GUO Chun-lan

2021, 41(8):  1231-1233. 

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Practice and theory are equally important in prosthodontics. Although the current training mode of residents in prosthodontics has made some achievements, there are still some challenges in the training. How to help residents master the essential elements of dental prosthodontics practice in a short term of training program, improve the quality of clinical training, and to provide more high-level prosthodontics doctors to the society are all important topics in the current dental prosthodontics traning. We designed a systematic head simulation teaching program to improve the clinical operating ability of residents in prosthodontics.

Medical students engagement during the COVID-19 pandemic and its enlightenment

YANG Shi-jie, XU Xie-qun

2021, 41(8):  1234-1237. 

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Medical education has experienced a tremendous impact during the COVID-19 pandemic. Global controversy continues to rage over whether and in what ways medical students should be involved in the prevention and control of the pandemic. This article reviews and summarizes the dilemmas of medical students during the COVID-19 pandemic and the actual engagement of medical students to provide a reference for medical education's response to major public health events.

Role of laparoscopic virtual simulator in the standard training for residents

ZHU Cai-lin, BI Wei-yun, CUI Xiao-hai, ZHANG Zhi-yong

2021, 41(8):  1238-1241. 

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Objective To explore the role of laparoscopic virtual simulator in the standard training of residents. Methods Twenty surgical attending physicians finished laparoscopic surgery independently with less than 10 cases and 20 residents in our hospital were selected as the research group. Laparoscopic skills training was conducted to all cases, the completion of laparoscopic cholecystectomy was compared between the two groups. Results The performance of surgical operations of the residents after training was better than before training (P＜0.05). The performance of surgical operations of the attending physicians after training neither is better than the residents physicians before training. Conclusions Laparoscopic virtual simulator can effectively enhance the skill of laparoscopic operation and reduce clinical risk.

Effect of web-based teaching on medical education during COVID-19 pandemic in China

LIU Yong-jian, TIAN Xin-lun, XU Kai-feng

2021, 41(8):  1242-1246. 

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Objective To review and evaluate the effect and learning outcomes of web-based teaching during COVID-19 pandemic and find the pathway of continuous development of teaching method to meet the learners' needs in future. Methods Eighteen questions included time period of web-based learning, effects, advantages and disadvantages of the learning, the willingness of students to accept web-based learning pathway. One hundred and eight medical students completed survey by response to the questionnaires. Results Only 12 students (11%) believed they could get 100% from web-based teaching as compared with face-to-face teaching, while 55 students (51%) believed they could get 80%-99% from their web-based teaching. Thirty-four students (31%) thought current web-based teaching did not bring their learning anxiety, but 30 students (28%) thought the web-based teaching brought their anxiety because of worrying not able to understand the courses thoroughly. Sixty-nine (64%) students would like to take the playback of the courses. The most common factor affecting the effect of web-based courses was absent-mindedness (64%), followed by trouble of internet access (57%). The advantages of web-based teaching courses included: flexible time (85%), freedom of place(83%), more comfortable learning environment (59%) and saving time (56%). Eighty-seven students (81%) were willing to obtain web-based teaching in their future medical learning, and only 21 students (19%) were reluctant to have web-based teaching. The higher the proportion of understanding of online courses compared to face-to-face courses, the more likely they were to choose online courses (P＜0.01). Students who felt anxiety because of worrying not learned thoroughly would not choose the web-based teaching (12/21 vs. 18/87, P＜0.01). Fail to keep concentration at learning was the main reason why students do not like online teaching in the future when the pandemic is over (7/21 vs. 75/87, P＜0.001). Conclusions During on the pandemic of COVID-19, most medical students thought web-based teaching is a feasible way to learn medical courses and can achieve relatively good effect.