Table of Content

05 December 2021, Volume 41 Issue 12

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Original Articles

Protective effect of FK506 combined with hypothermic mechanical perfusion on donor liver of rats

JIANG Li, LI Jian-hui, YU Hao, LI Hao-yu, XIE Hai-yang, ZHOU Lin, ZHENG Shu-sen

2021, 41(12):  1715-1718. 

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Objective To investigate the protective effects of FK506 combined with low temperature mechanical perfusion on the reduction of ischemia reperfusion injury of rat liver transplants. Methods SD rats were divided into HTK group and FK506 + HTK group. Orthotopic liver transplantation was performed 3 hours after machine perfusion of 150 mL HTK (HTK group) or FK506+150 mL HTK (FK506 + HTK group). Blood samples were collected at 3 and 24 hours after transplantation in both groups, and serum samples were centrifuged for liver function test. Twenty-four hours after transplantation, liver tissues were collected and fixed with formalin for HE staining. Results Serum ALT levels in FK506+HTK group were significantly lower than that in HTK group (P＜0.05). Inflammatory infiltration in FK506+HTK group was less than that in the HTK group, and the liver structure was intact. Conclusions FK506 added into perfusate for machine perfusion of the donor liver can effectively reduce liver function damage and inflammation damage within 3 hours after transplantation, and has a certain protective effect on the liver.

miR-29b inhibitor reduces cholesterol synthesis of liver in mice

CAI Jun-yan

2021, 41(12):  1719-1723. 

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Objective To investigate the effects and mechanism of miR-29b on the cholesterol synthesis in the liver of hypercholesterolemia mice. Methods C57/BL6 mice were divided into 6 groups: 10 in control group was fed with normal diet, 10 in HF group was fed with Paigen diet, 6 in Con+shRNA group, 6 in Con+antago group, 6 in HF+shRNA group and 6 in HF+antago group. The Con+shRNA group and HF+shRNA group were injected with scrambled shRNA (2.5 mg/kg); Con+antago group and HF+antago group were injected with miR-29b antagomir (2.5 mg/kg). Total cholesterol in the plasma and liver was measured after 8 weeks. RT-qPCR was used to detect expression of miR-29b and SIRT1. Western blot was used to detect the expression of proteins relating cholesterol synthesis in the liver. Results 1) Compared with the control group, the HF group showed increased expression of miR-29b in the plasma and liver. 2) Compared with the HF+shRNA group, the total cholesterol in the plasma and liver of the HF+antago group decreased. miR-29b antagomir increased SIRT1 mRNA and protein expression in the liver. Along with elevated SIRT1 expression, SREBP2 mRNA and protein expression were decreased. Consistently, the expression of HMGCR was reduced by miR-29b antagomir. Conclusions The expres- sion of miR-29b is increased in liver tissue of hypercholesterolemia mice and miR-29b inhibitor can reduce cholesterol synthesis in the liver.

Over-expression of TREM2 alleviates cognitive impairment after traumatic brain injury in rats

YANG Qi, XU Feng, JIAO Yang, ZHANG Sai, SUN Zhong-lei

2021, 41(12):  1724-1729. 

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Objective To explore the effect of over-expression of triggering receptor on dementia model after traumatic brain injury (TBI) in rat model and potential mechanism. Methods Rats were randomly divided into control group and TBI test groups of 2, 5, 7, 14 and 28 days (n=8). RT-qPCR and Western blot were used to detect trem2 mRNA and protein levels in brain tissues. The remaining 32 rats were randomly divided into 4 groups (n=8): control group, TBI group, (TBI+Null) group and (TBI+ TREM2) group. The (TBI+Null) group was injected with control lentiviral vector, and the (TBI+TREM2) group was injected with the same amount of lentiviral vector encoding TREM2. The memory function of rats in each group was assessed by Morris water maze, and the expression of microglia phenotypes (iNOS and Arg-1), neuroinflammatory related factors(IL-1β, IL-6, IL-4 and IL-10) and cognition-related proteins [amyloid β1-42 (Aβ1-42) and tau] in brain tissues of rats from each group were assessed by RT-qPCR and Western blot. Results Compared with the control group, the expressions of TREM2, TREM2 mRNA, mean escape latency, iNOS, IL-1β, IL-6, Aβ1-42 and Tau were all increased in TBI group, while the expression of Arg-1, IL-4 and IL-10 significantly decreased (P＜0.05). (TBI+TREM2) group significantly alleviated the mean escape latency, increased expression of iNOS, IL-1β, IL-6, Aβ1-42 and Tau, and decreased expression of Arg-1, IL-4 and IL-10 (P＜0.05). Conclusions TREM2 over-expression can regulate the microglial phenotype in brain tissue of TBI rats, reduce the expression of cognition-related proteins (Aβ1-42, tau), and improve the learning and memory function of the animal model.

Effect of matrine on proliferation and migration of human thyroid cancer cell line TPC-1

FU Song-bo, MA Cheng-xu, JING Gao-jing, ZHAO Nan, TANG Xu-lei, MOU Jun-qin, CHANG Yin-long

2021, 41(12):  1730-1735. 

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Objective To investigate the mechanism of matrine inhibiting the proliferation and migration of thyroid cancer cell line TPC-1 through down-regulated miRNA-182-5p TPC-1. Methods TPC-1 cells were transfected after 24 hours with 0.5 mg/mL matrine or without 0.5 mg/mL matrine, the experiments were divided into: inhibitor-NC, inhibitor against miR-182-5p (inhibitor), mimic-NC, miRNA-182-5p-mimics, mimic-NC+matrine and miR-182-5p- mimics+matrine. miR-182-5p, E-cadherin, N-cadherin and vinmentin gene were detected by PCR. TPC-1 cells proliferation and migration were detected using CCK-8 and Transwell assay. The expression of E-cadherin、N-cadherin and vinmentin protein was determined by Western blot. Results Compared with Nthy-ori3-1 (NT), miR-182-5p was highly expressed in TPC-1 cells (P＜0.01); down-regulation to the expression of miRNA-182-5p inhibited the proliferation and migration of TPC-1 cells (P＜0.01); Compared to the 0 mg/mL matrine group, 0.5 mg/mL matrine significantly reduced the miR-182-5p level (P＜0.05) and inhibited proliferation, migration of TPC-1 cells and also reduced N-cadherin and vinmentin expression but increased E-cadherin expression in TPC-1 cells (P＜0.01); Over-expression of miR-182-5p partly abolished the matrine-inhibited proliferation and migration of TPC-1 cells and the increased E-cadherin expression, decreased miR-182-5p,N-cadherin and vinmentin expression (P＜0.01). Conclusions Matrine is a potential therapeutic drug for papillary thyroid carcinoma (PTC) and miR-182 may be an effective target for the treatment of PTC.

CTRP6 deficiency alleviates CCl₄-induced liver fibrosis progression in mice

CAI Huan-chang, ZHOU Dan-ru, SHI Tian-jing, YIN Ya-jun, ZHANG Da-wei, ZHANG Jin

2021, 41(12):  1736-1741. 

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Objective To explore the role and underlying mechanism of C1q/TNF-related protein 6 (CTRP6) in the development process of liver disease. Methods The histopathological examination and biochemical indexes of injured livers from wild-type (CTRP6^+/+) and knockout (CTRP6^-/-) mice induced by intragastric administration of CCl₄ were analyzed. RT-qPCR was used to detect the expression of the fibrosis marker genes (Acta2, Col1al, Mmp2 and TGF-β) and cell proliferation marker genes (Cyclin D, Cyclin E and CDK6). Results Compared with CTRP6^+/+ mice, the hepatocytes in CTRP6^-/- mice showed mild necrosis, looseness and swelling. The high SOD activity and low MDA level were also observed in CTRP6^-/- mice liver. Meanwhile, the expression of fibrosis and cell proliferation markers in CTRP6^-/- mice were significantly lower than those in CTRP6^+/+ mice. Conclusions CTRP6 gene is closely related to liver disease development, and the liver fibrosis progression induced by CCl₄ is alleviated by its deletion. The mechanism may be explained as that CTRP6 knockout affects the proliferative capacity of hepatocytes.

Dapagliflozin decreases myocardial endoplasmic reticulum stress and relieves left ventricular remodeling in rats with heart failure

ZHANG Zhi-min, GUO Li-sha, MA Li-qun, REN Ke, LU Jun, WEI Xing, LI Hui-jie, ZHOU Sheng-hua

2021, 41(12):  1742-1748. 

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Objective To observe the influence of dapagliflozin on ERS of myocardial tissues from rats with heart failure, and explore the its relationship with myocardial remodeling. Methods The rats were divided into the control group, model group (with aortic coarctation, TAC) and Dapagliflozin intervention group (with Dapagliflozin 0.5 and 1.0 mg/kg given by gavage once daily). Non-invasive rat tail artery manometer was used to detect mean arterial pressure. Weigh body weight, whole heart weight and left ventricular weight were recorded to calculate the rat myocardial hypertrophy index HWI and LVWI. Small animal ultrasound was used to detect rat heart function. The morphological changes of cardiomyocytes was microscopied with HE staining. Immuno-histochemistry and Western blot were used to detect GRP78 and CHOP expression in rat myocardial tissue. Results Compared with the control group, MAP, HWI and LVWI in the model group were significantly increased (P＜0.01), EF and FS decreased significantly (P＜0.01). Compared with the model group, HWI and LVWI were reduced (P＜0.05), EF and FS were increased (P＜0.05) in dapagliflozin group. HE staining showed that the myocardial fibers in control group were neatly arranged and morphologically regular; in model group, the myocardial fibers were excluded from the disorder, the morphology was irregular, and the tissue was evacuated; the myocardial fibers in dapagliflozin group were better than that of model group. Compared with control group, the expression of GRP78 and CHOP in the myocardium of model group was significantly increased(P＜0.01);compared with model group, the expression of GRP78 and CHOP in dapagliflozin group was reduced (P＜0.05). Conclusions Dapagliflozin obviously inhibits ERS, down-regulates the expression of GRP78 and CHOP, protects cardiomyocytes, more effectively relieves ventricular remodeling and improves cardiac function. ERS may be one of the molecular biological mechanisms of Dapagliflozin.

miR-493-5p inhibits the proliferation and migration of human ovarian cancer cell line SKOV3

LI Shao-ru, QIN Hai-xia, LIU Shan-shan, HOU Rui-jie

2021, 41(12):  1749-1755. 

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Objective To investigate the effects of miR-493-5p on proliferation, invasion and migration of ovarian cancer cells and underlying mechanism. Methods Culture human normal ovarian epithelial cell lines IOSE80 and ovarian cancer cell lines A2780, SKOV3, OVCAR3, transfected the miR-493-5p over-expression vectors, miR-493-5p suppressed expression vectors and G protein coupled receptor kinase interacting factor 1 (GIT1) over-expression vectors into SKOV3 cells; RT-qPCR was used to detect miR-493-5p and GIT1 mRNA expression; Western blot was used to detect protein expression; MTT assay was used to detect cell viability; Transwell was used to detect cell migration and invasion; dual luciferase report experiment was applied for detection of the targeting relationship between miR-493-5p and GIT1. Results In ovarian cancer cells A2780, SKOV3, OVCAR3, miR-493-5p were weakly expressed, and GIT1 was highly expressed (P＜0.05); After over-expression of miR-493-5p, the proliferation activity, migration and invasion number of ovarian cancer cell SKOV3 were decreased (P＜0.05). miR-493-5p targeted at the regulation of GIT1 expression, and over-expression of GIT1 reduced the inhibitory effect of miR- 493-5p on proliferation, migration and invasion of ovarian cancer cell SKOV3 and expression of p-MEK1/2, p-ERK1/2, pc-Jun and pc-Fos. Conclusions miR-493-5p can inhibit the proliferation, migration and invasion of ovarian cancer cells SKOV3. The mechanism may be related to the targeted regulation of GIT1 and MEK1/2-ERK1/2 pathway, which thus provides some new targets for diagnosis, prevention and treatment for ovarian cancer.

miR-146a alleviates apoptosis of myocardial cells in rats with myocardial ischemia-reperfusion injury

ZHENG Xin, YU Hai-bo

2021, 41(12):  1756-1761. 

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Objective To investigate the mechanism of miR-146a on the level of serum myocardial enzyme, Toll-like receptor 4 (TLR4) genes and apoptosis of myocardial cells in rats with myocardial ischemia-reperfusion injury (MI/RI). Methods Thirty-six rats were divided into sham operation group (sham), model group (model), miR-146a NC group (transfected with miR-146a-NC after ligation) and miR-146a agomir group (transfected with miR-146a-a agomir after ligation).Myocardial infarct size was measured by TTC staining, the mRNA expression of miR-146a/TLR4 in myocardial tissue was detected by RT-qPCR and cardiomyocyte apoptosis was microscopied by TUNEL staining.The activity of lactate dehydrogenase (LDH), troponin (cTnT) and creatine kinase isoenzyme (CK-MB) in serum was determined by colorimetry.TLR4 protein expression in myocardial tissue was detected by Western blot. Results Compared with sham operation group, the area of myocardial infarction (white) in model group was increased (P＜0.05). While the area of myocardial infarction (white) in miR-146a agomir group decreased (P＜0.05), and the mRNA expression of miR-146a in the model group was decreased (P＜0.05), the miR-146a mRNA expression was increased in miR-146a agomir group (P＜0.05);Compared with the sham operation group, the myocardial muscle fibers were broken and swollen, the interstitial hyperemia was obvious, the structure disappeared, and the boundary of multiple cell necroses was not clear.Compared with the model group, the myocardial tissues of miR-146a agomir group were neatly arranged, and pathology such as edema was improved, the activities of LDH, cTnT and CK-MB, the apoptosis rate of myocardial cells and the protein expressions of TLR4, tumor necrosis factor-α (TNF-α) and nuclear factor-κB (NF-κB) in serum of the model group were increased (P＜0.05).Compared with model group, the above indexes in miR-146a agomir group were decreased (P＜0.05). Conclusions The expression of miR-146a is low in the myocardial tissue of MI/RI, and over-expression can reduce the activity of serum myocardial enzyme spectrum and TLR4 expression, thereby reducing the apoptosis of cardiomyocytes and protecting the heart.

lncRNA RAB11B-AS1 up-regulating miR-628-3p inhibits proliferation and migration of gastric cancer cell line

YANG Ning-bo, JIA Xiao-dong, KOU Yao

2021, 41(12):  1762-1766. 

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Objective To explore the effect and molecular mechanism of lncRNA RAB11B-AS1 on gastric cancer cell proliferation, migration, invasion and cisplatin sensitivity. Methods The cisplatin-resistant gastric cancer cells (HGC-27/DDP) were divided into control group, si-NC group, and si-RAB11B-AS1 group; tetra-methylazolium salt colorimetric assay(MTT) was used to detect cell survival rate; real-time fluorescence quantitative PCR (RT-qPCR) was applied to detect the expressions of RAB11B-AS1 and miR-628-3p; flow cytometry was used to detect cell cycle; cell migration and invasion were examined by Transwell cell method and dual luciferase report experiment was applied to detect the targeting relationship between RAB11B-AS1 and miR-628-3p. Results The survival rate of HGC-27 cells was significantly reduced after 0.2 and 0.4 mg/L cisplatin treatment (P＜0.05), but the survival rate of HGC-27/DDP cells after 0-0.4 mg/L cisplatin treatment was not statistically changed. The expression of RAB11B-AS1 in HGC-27 andHGC-27/DDP cells was significantly increased (P＜0.05), and the expression of RAB11B-AS1 in HGC-27/DDP cells was significantly higher than that of HGC-27 cells (P＜0.05). Interfering with the expression of lncRNA RAB11B-AS1, the proportion of G₀-G₁ phase cells was increased significantly, the proportion of S phase cells was decreased significantly (P＜0.05). Both cell survival rate and the number of migrating and invasive cells were significantly reduced (P＜0.05). RAB11B-AS1 was found to specifically regulate miR-628-3p. Conclusions LncRNA RAB11B-AS1 can inhibit the proliferation, migration and invasion of gastric cancer cells by up-regulating the expression of miR-628-3p, and increase the sensitivity of cancer cells to cisplatin.

Lycorine hydrochloride inhibits the proliferation, migration and invasion of gastric cancer cell line MGC-803

BAO Mei-mei, XU Wen, WANG Chao, WANG Jia, MIAO Xiao-fen

2021, 41(12):  1767-1773. 

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Objective To investigate the effect of lycorine hydrochloride (LH) on the proliferation, migration and invasion of human gastric cancer cell line MGC-803 and its possible mechanism. Methods Cell proliferation ability was detected by MTT assay and colony formation assay. Distribution of cell cycle was detected by flow cytometry. The migration ability of cells was detected by wound healing assay. Transwell assay was used to detect the invasion ability of cells. RT-qPCR was used to detect the effects of LH on gene expression of cell migration and invasion. Results The inhibitory rate of LH on MGC-803 cells was concentration and time dependent (P＜0.05, P＜0.01), and the IC₅₀ value at 48 h was 3.76 μmol/L. The colony formation of MGC-803 cells was significantly inhibited by LH, and the colony formation was completely inhibited when the concentration reached 20 μmol/L (P＜0.01). Cell cycle was arrested in S phase after LH treatment (P＜0.01). With the increase of LH concentration, cell migration and invasion were significantly inhibited (P＜0.01), the expression level of miR-203 gene was up-regulated, while the expression levels of Slug, MMP2 and MMP9 were down-regulated in a concentration-dependent manner (P＜0.05, P＜0.01). Conclusions LH significantly inhibited the proliferation of MGC-803 cells, induced cell cycle arresting in the S phase, and inhibited cell migration and invasion. The expression level of miR-203 gene was up-regulated.

Chlorgenic acid inhibits TGF-β1-induced fibrotic factors expression of human renal tubular epithelial cell line HK-2

SUN Meng-kui, LI Shou-lin

2021, 41(12):  1774-1779. 

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Objective To explore the effects of Chlorgenic acid (CGA) on TGF-β1 induced the change of human renal tubular epithelial HK-2 cell fibrotic factors change and the underlying mechanism. Methods HK-2 cells were cultured in vitro. CCK-8 assay was conducted to detect cell proliferation. Immunofluorescence assay was used to detect the expression of collagen Ⅰ and collagen Ⅲ. RT-qPCR was used to detect mRNA expression of HK-2 cell fibrosis related genes. Western blot assay was carried out to detect protein expression of TLR4/NF-κB pathway. Results The proliferation rate of cells in different CGA treated groups at different time points showed no differences. The expression of collagen Ⅰ,collagen Ⅲ,α-SMA,vimentin,TGF-β1,snail and slug increased while E-cadherin decreased in TGF-β1 group(P＜0.05). CGA reversed these expression changes induced by TGF-β1. Further, CGA inhibited TGF-β1 induced TLR4, p-IκBα and p-NF-κB expression (P＜0.05). Conclusions Chlorgenic acid can inhibit TGF-β1 induced increase of fibrotic factors expression in human renal tubular epithelial HK-2 cell through suppressing activation of TLR4/NF-κB pathway.

FOXM1 promotes proliferation, migration and invasion of endometrial cancer cell line HEC-1B

HUANG Bo, CHENG Bi-heng, XIE Mei-ting, LIU Shan-shan, WEI Min

2021, 41(12):  1780-1785. 

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Objective To explore the effect of inhibiting the expression of forkhead box protein M1 (FOXM1) gene on the proliferation, migration and invasion of endometrial cancer cell line HEC-1B. Methods Human endometrial carcinoma cell line HEC-1B was selected as the subject and divided into three groups: blank control group, negative control group and siRNA-FOXM1 group. Real-time qPCR was used to detect the expression of FOXM1, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) mRNA in cells of each group. CCK8 method was used to detect the proliferation of cells. Cell scratch test to detect the ability of cell migration in each group. Transwell chamber method was performed to detect the invasion ability of cells in each group. The protein expression of VEGF and bFGF were detected by Western blot. Results Compared with HEECs, the expression of FOXM1 mRNA and protein in HEC-1B cells was significantly increased (P＜0.05). The expression of FOXM1 mRNA and protein, proliferation, migration and invasion ability of HEC-1B cells were significantly lower than those of blank control group and negative control group (P＜0.05). The mRNA and protein expressions of VEGF and bFGF in hec-1b cells were significantly decreased after FOXM1 expression was inhibited (P＜0.05). Conclusions Inhibiting of FOXM1 expression can inhibit the proliferation, migration and invasion of HEC-1B cells, and the mechanism might be related to inhibiting the expression of VEGF and bFGF.

Effect of inhibiting miR-155 on apoptosis and inflammation reaction in myocardial ischemia-reperfusion model

ZHU Xin-hua, LIU Bei-bei, HOU Jing-wen, LI Qiu-ying, XU Hui-juan, ZHANG Xiao-yang

2021, 41(12):  1786-1791. 

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Objective To explore the effect of inhibiting miR-155 on cardiomyocyte apoptosis and inflammation in myocardial ischemia-reperfusion (MI/R) model. Methods Myocardial cells of H9c2 rats were divided into four groups: blank control group, myocardial ischemia-reperfusion group (MI/R group), negative control group and miR-155 inhibitor group. The expressions of miR-155, NF-κB signaling pathway related genes and Bax, Bcl-2 mRNA were detected by RT-qPCR. The contents of IL-8 and TNF-α were detected by ELISA. Western blot was used to detect the expression of NF-κB signaling pathway related genes and Bax, Bcl-2 protein. Results Compared with the control group, the expression of miR-155 in MI/R group was significantly increased (P＜0.05) while the expression of miR-155 in miR-155 inhibitor group was significantly decreased (P＜0.05). In MI/R group, the apoptosis rate, the content of IL-8 and TNF-α, the protein and mRNA expression of Bax and NF-κB signal pathway were significantly higher than those in the control group, while the protein and mRNA expression of Bcl-2 were lower (P＜0.05). After inhibition the expression of miR-155, the apoptosis rate, the content of IL-8 and TNF-α, the protein and mRNA expression level of Bax and NF-κB signal pathway related gene were significantly decreased, while the protein and mRNA expression by Bcl-2 were increased (P＜0.05). Conclusions Inhibition of miR-155 expression can protect MI/R injury through inhibition of apoptosis and inflammation. The potential mechanism is the inhibition of the activation of NF-κB signaling pathway.

Curcumin enhances the radio-sensitivity of prostate cancer cell line PC-3

CHENG Ji, FU Guo, ZHAO Hua-cai, WANG Zhi-gang, GAO Dan, DONG Qing-chuan

2021, 41(12):  1792-1796. 

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Objective To explore the molecular mechanism of curcumin increasing the radiosensitivity of prostate cancer PC-3 cells. Methods Prostate cancer PC-3 cells were cultured and treated with curcumin, irradiation or combined therapeutic methods to observe the proliferation, apoptosis and change of cell cycle of PC-3 cells shown by MTT,RT-qPCR and FCM. Results Compared with control group, the cells from the radiation or curcumin group, the survival rate, the level of PCNA mRNA and Cdc2 mRNA were decreased (P＜0.05), and the ratio of S phase and G₂/M phase, caspase-3 and caspase-9 activity and the apoptosis rate were increased (P＜0.05); Compared with the cells in the radiation group, after treated with curcumin combined with radiotherapy, the survival rate, the level of PCNA mRNA and Cdc2 mRNA were decreased (P＜0.05), and the ratio of S phase and G₂/M phase, caspase-3 and caspase-9 activity and the apoptosis rate were all increased (P＜0.05). Conclusions Curcumin has a certain radiosensitizing effect in vitro, which potentially strengthen the inhibitory effect of radiotherapy on the growth of prostate cancer PC-3 cells.

Clinical Sciences

Predictive factors of early death in patients with craniocerebral injury

LIU Jia-wei, ZHANG Yi, WANG Kai, MA Wen-juan

2021, 41(12):  1797-1801. 

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Objective The predictive factors of early death in patients with craniocerebral injury (CI) were analyzed to provide a reference for clinical treatment. Methods Collected clinical data from 1 102 patients with craniocerebral injury and admitted into the Department of Neurological Surgery, First Affiliated Hospital of Shaanxi University of Chinese Medicine from January 2014 to December 2019, and analyzed the correlation of general data, injuries, and auxiliary examinations that may affect patients' early death, Using multi-factor Logistic regression analysis to influence the predictive factors of early death in patients with craniocerebral injury. Results Among them, 104 CI patients died after early rescue, accounting for 9.4% of the total number. Abnormal pupil responses (OR=4.669, P＜0.05), midline shift (OR=7.898, P＜0.001), brain herniation (OR=8.013, P＜0.001),lower GCS score (OR=3.847, P＜0.001), multiple trauma (OR=6.354, P＜0.01), coagulopathy (OR=5.281, P＜0.01), and abnormal blood sugar (OR=6.574, P＜0.01) are risk factors for early death. Conclusions Patients with low GCS score, slow or absent pupil light reflex, midline deviation, cerebral hernia, abnormal blood glucose and abnormal blood coagulation and multiple injuries are predictive factors for early death of craniocerebral injury, early intervention is encouraged as a tackling to the challenge.

Clinical observation of apatinib in the treatment of metastatic colorectal cancer

CHEN Zhu, LIU Yan, GAO Li-hua, CHEN Bu-you, TANG Ai-hua, LIU Jun

2021, 41(12):  1802-1806. 

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Objective To evaluate the efficacy and safety of apatinib in the treatment of metastatic colorectal cancer (mCRC). Methods Sixty-five patients with mCRC treated with apatinib were enrolled in this study for retrospective analysis. The factors affecting the recent effective, progression-free survival (PFS) and adverse reactions were evaluated. Results The disease control rate in 63 evaluable patients was 69.9%. The median PFS for patients received first-line, second-line, and third-line and above apatinib treatment were 9.3 months, 5.8 months, and 3.3 months, respectively(P＜0.001). The PFS in the apatinib group and the apatinib/chemotherapy combination group in the third-line and above treatment were 2.9 months and 3.3 months, respectively. There was no significant difference in serum cholinesterase and albumin concentrations between patients with liver metastasis before and after treatment. Adverse reactions were mainly grade 1 to 2 hypertension, proteinuria, myelosuppression and hand-foot syndrome. Conclusions Apatinib is an effective treatment with controllable toxicity for mCRC, which has mild adverse effect on liver reserve function.

Mini Reviews

Research advance of myokines on bone metabolism regulation

ZHOU Bing-na, LI Mei

2021, 41(12):  1809-1812. 

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Bone and muscle are closely interrelated.Muscle can synthesize and secrete a series of myokines,which play important roles on the growth,development and function of the bone.Myokines can regulate the function of osteoblasts,osteoclasts and osteocytes,which can be divided into factors that promote bone anabolism,increase bone catabolism or regulate bone turnover in a double-edged way.This article reviews the advance of myokines which have important regulatory effects on bone metabolism,to reveal the regulatory network between muscle and bone,and provide new targets for the treatment of musculoskeletal diseases.

Research progress on the role of glutamate transporter in the pathogenesis of Parkinson's disease

MA Li-fang, LIANG Jian-qing, HE Jian-cheng, SUN Xue, LIANG Peng

2021, 41(12):  1813-1817. 

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The excitotoxicity mediated by glutamate (Glu) is the main pathogenesis of Parkinson’s disease (PD), and the glutamate transporter is the key factor regulating the process of Glu excitotoxicity. Therefore, glutamate transporters may be involved in the pathogenesis of PD and play an important role in the process. Therefore, understanding the role of glutamate transporters in the pathogenesis of PD may provide new ideas for later drug research and development targeting at glutamate transporters.

Research progress on mitochondrial translocation of human telomerase reverse transcriptase

HU Wei-kai, LIU Rui-xia, YIN Cheng-hong

2021, 41(12):  1818-1822. 

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Telomerase reverse transcriptase is a subunit of telomerase, which plays an important role in activating telomerase and regulating cell cycle. Human telomerase reverse transcriptase(hTERT) is mainly expressed in germ cells, embryonic stem cells and tumor cells, only a few expressed in normal cell. hTERT is mainly located in nucleus and also distributed in mitochondria. hTERT migration from nucleus into mitochondria is called the mitochondrial translocation of hTERT. Mitochondrial translocation of hTERT functions in the process of apoptosis, immortalization and drug resistance. Control of hTERT is a potential breakthrough in the treatment of diseases.

Research progress on the role of mitochondrial fusion protein Mfn2 in diabetic nephropathy

LI Meng-jie, KE Ben, LONG Mai, FANG Xiang-dong

2021, 41(12):  1823-1827. 

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Diabetic nephropathy (DN) is one of the serious complications of diabetes, and mitochondrial dysfunction is a core factor in the development of DN. Mitochondrial fusion protein-2 (Mfn2) is a mitochondrial fusion protein that locates in the outer membrane of the mitochondria and plays an important role in maintaining the structure and function of the mitochondria. Mfn2 can inhibit mitochondrial morphology and dysfunction by reducing oxidative stress, endoplasmic reticulum stress and autophagy, save the cells from damages caused by apoptosis and delay the occurrence and development of DN, so it may become a potential target for DN treatment.

Advances in the role of SIRT3-mediated mitochondrial function and metabolic regulation in diabetes mellitus type 2

YANG Jing, LI Min

2021, 41(12):  1828-1832. 

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Diabetes mellitus type 2(T2DM) has a high morbidity because there is no specific treatment. Mitochondrial injury and metabolic disorder are the most important pathophysiological manifestations of T2DM. So it is essential to maintain mitochondrial function and cell metabolic homeostasis. Mitochondrial deacetylase silence information regulator 3 (SIRT3) is crucial for the regulation of respiratory enzymes, for antagonizing oxidative stress and promoting mitochondrial autophagy as well as glucose uptake.

Research progress in regulation of non-steroidal anti-inflammatory drugs on immunocytes

YU Jing, LIU Ke, WANG Hai-yan, YAN Jun

2021, 41(12):  1833-1837. 

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Non-steroidal anti-inflammatory drugs (NSAIDs) are widely applied in the treatment of inflammation, fever and for pain relief based on its efficacy in anti-inflammatory, anti-rheumatic, analgesic, antipyretic, and anticoagulation. Moreover, the relationship between NSAIDs and immune cells is quite important since. NSAIDs can negatively regulate B cell proliferation via inhibiting prostaglandin (PG), improve the imbalance of Th1/Th2 and immunologic derangement caused by Th17 differentiation, inhibit release of TNF-α by macrophages and decrease the level of tumor necrosis factor (TNF)-α, influence inflammation via controlling other inflammatory cytokines. In addition, the mechanism may be concerned with several signal pathways including PGE2 receptor 2 (PGE2-EP2), 5-hydroxytryptamine(5-HT), glucagon-like peptide-2 (GLP-2) and nuclear factor kappa-B-interleukin-6- signal transducer and activator of transcription 3 (NF-κB-IL-6-STAT3). Thus, it is necessary to further investigate the regulation and mechanism of NSAIDs on various immunocytes, potentially provide a new strategy to optimize immune funtions under trauma and disease.

Research progress of mitochondrial transplantation

WANG Yi-chuan, LIU Xiao-jing, YE Feng, YANG Xue-liang, CHEN Na, WU Jian-hua, LI Yan-lin

2021, 41(12):  1838-1842. 

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Mitochondria provides most of the energy to drive cell function, and its dysfunction can lead to a variety of disease. Since mitochondria has been proved to be able to transfer between cells, mitochondrial transplantation has become an innovative idea for the treatment of mitochondrial dysfunction and this technology has been supported by evidences from animal experiments. The transplantation of mitochondrial is potentially applied in the treatment of disease of various tissues including heart, liver, lung and brain.

COVID-19 and hyponatremia

LIANG Si-yu, CHEN Shi, PAN Hui, JIAJUE Rui-zhi, ZHU Hui-juan

2021, 41(12):  1843-1847. 

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The worldwide spread of coronavirus disease 2019 (COVID-19) has caused a heavy burden on the public health of all countries. As the specific antiviral treatment is not available, it is necessary to monitor various clinical indicators, and minimize the risk factors related to poor outcomes in the management of COVID-19. COVID-19 is often presented with hyponatremia which is frequently associated with prolonged hospitalization, increased rate of intensive care unit transfer, higher risk of severe pneumonia and mortality. Hyponatremia is an important index for early identification of patients with poor prognosis. COVID-19 related hyponatremia is mainly caused by inappropriate antidiuretic hormone secretion syndrome and hypovolemia. If hyponatremia can be diagnosed and corrected in time, the poor clinical outcomes related to hyponatremia can be prevented.

Medical Education

Exploration of “scientific research back-feeding teaching” in undergraduate teaching of neurobiology

LIU Ling, WU Sheng-xi, XUE Qian, KUANG Fang

2021, 41(12):  1848-1851. 

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Under the global wave of brain science development, neurobiology, an important part of “brain project” needs strong support from existing neurobiologists and new blood infusion. Therefore, teaching of neuroscience becomes crucial. Combined with the characteristics of neurobiology teaching and scientific research in military colleges, a mode of “scientific research back-feeding teaching” was carried out. Through the integration of scientific spirit, scientific thinking, support of scientific research platform and off-curricular scientific projects into the multi-level teaching practice, the effect of scientific research back-feed teaching is significant, and the back feeding of scientific research to teaching greatly stimulates the students'learning interest of brain science, and improves the teaching quality, which also greatly supports the training of brain science talents.

Application and exploration of functional experiment teaching based on virtual experiment system during COVID-19 pandemic

CHEN Yu-cai, GUO Jian, ZHU Qing-wen, CHENG Wei

2021, 41(12):  1852-1855. 

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During the pandemic of COVID-19, in order to respond to the call of the Ministry of Education that “teaching and learning are not stopped even though courses are stopped”, universities across the country have launched online teaching. Taking the “functional experiment” course in Beijing University of Traditional Chinese Medicine as an example, this course was carried out using online virtual experiment platform. On the basis of experimental teaching during the pandemic, teachers have collected experience and students' feedback. This paper summarizes the strengthens and weakness of this teaching method during the pandemic.

Investigation and analysis on the status of heart sound auscultation and training needs of medical students

LIN Xue, ZHANG Xiao, LIU Ji-hai, ZHANG Hui, QIAN Xiao-jing, XIAO Ran, FANG Li-gang

2021, 41(12):  1856-1859. 

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Objective To clarify the current direction of improvement of heart sound auscultation teaching. Methods Questionnaire survey was conducted on the students of Peking Union Medical College who had studied diagnostics. At the same time, two tests of heart sound auscultation for medical students were collected. Two teams of residents were interviewed to investigate the mastery of medical students in heart sound auscultation and learning problems. Results Forty-seven students answered the questionnaire. A total of 177 test scores in the diagnostic heart sound section of the medical students of two grades were collected. Ten residents from the two interview teams participated in the interview. There are 87.2% of students think sound auscultation is very important in the clinical. The teaching of diagnostics for heart sounds is mainly explained by the teacher by demonstration of heart sound recordings and language descriptions, but only 53.2% of students learn some of the content and, 4.3% students said that they did not learn at all. There are 44% of the students who are able to answer correctly in the heart sound case examina- tions,nearly 80% of medical students and residents were not confident in understanding heart sounds. About 76.6% of students would look for special heart sound teaching software and audio for further study, but only 6.4% of students thought that such teaching materials and software were of great help, mainly due to the distortion of heart sounds provided by auxiliary teaching materials. Medical students hope that teachers provide effective heart sound software, real heart sound databases, and a large number of cases supplemented with medical history and imaging examination results to support their clinical reasoning; medical students also hope to obtain more bedside auscultation opportunities. Conclusions The article presented here showed shortcomings of the existing heart sound teaching, and provide some evidence from learners' side to improve learning outcomes.

Explore an integrated pattern of profession and humanity for otorhinolaryngology education

TIAN Xu, FENG Guo-dong, HUO Hong, WANG Jian, YANG Hua, GAO Zhi-qiang, LUO Lin-zhi

2021, 41(12):  1860-1863. 

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Objective To explore a new pathway of otorhinolaryngology training which combines medicine and humanity and made balance between the two systems. Methods The content of humanity and history was added into the classic courseware and class discussion. Then the effects of this new model were evaluated using a system for evaluation of otolaryngology teaching qualities. Results Otorhinolaryngology training with the new model was highly applauded by students, especially in the aspects of innovation and motivation. Improvements were needed for anatomy and the class atmosphere. Conclusions Combination of medicine and humanity motivates the students a lot and build their consciousness of humanity, which facilitates their self-regualted learning. This new education model is worth more promotion and popularization.

Impact of comprehensive teaching mode and trainer experience on teaching effect of basic surgical skill training

WANG Chang-jun, LIN Yan, ZHOU Yi-dong, ZHAO Jun, JIANG Ying-zi, LUO Lin-zhi, SUN Qiang

2021, 41(12):  1864-1867. 

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Objective To study the impact of comprehensive teaching mode and trainer experience on teaching effect of surgical basic technique training. Methods The present study adopted 2×2 factorial design. Seventy surgical interns were randomly assigned to the control group adapting lecture-based learning and the experimental group was trained with the comprehensive teaching mode integrating lecture-based, problem-based and case-based learning. Each study group was further randomly divided into two subgroups with either resident or attending surgeon as trainers. Results The comprehensive teaching mode was superior to the control group in terms of quantitative subjectobject assessment and operation time consumption, especially for “willingness to pursue a career in surgery” “clinical reasoning” and “direction of future development”. Furthermore, except for “clinical reasoning”, the teaching effect of resident didn't show statistically significant difference with attending surgeon. Conclusions The comprehensive teaching mode exhibits better teaching effect as compared with the classoc lecture-based learning. The surgical resident is fully competent to serve as the trainer for surgical basic technique training program.

Influence of screen teaching on children's psychological and behavior problems

CHEN Lu, ZHU Hui-juan, CHEN Shi, ZHANG Mei, BAN Bo, YANG Yan-jie, PAN Hui

2021, 41(12):  1868-1870. 

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In winter of 2020, government delayed the opening of schools because of the pandemic of COVID-19. In order to regulate children's mood, parents provided their children with the chance to use electronic products such as mobile phones. Educational systems across the country organized students to take part in online learning. Screen teaching is helpful for children to complete learning. But some children require an additional use of mobile phones or electronic products for entertainment and games. However, a longtime screen use will bring negative influence on psychological behaviors of children and affect their growth. In order to protect children, schools should set up online courses reasonably according to children's physical and mental characteristics. And parents should enrich home activity to meet the needs of children and take effective measures to minimize negative impact to children.