Basic & Clinical Medicine

Inhibitory effect of histone H3K27 methylation on proliferation of human well-differentiated nasopharyngeal carcinoma cell line CNE-1

CAI Bo, XING Juan-juan, HU Rong, REN Xin, WANG Rong, WU Tian-ning, GUO Fei, CHEN Shao-qing

2020, 40(12): 1613-1618.

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Objective To investigate the effects of inhibiting histone H3K27me3/2 demethylase on proliferation of well-differentiated human nasopharyngeal carcinoma cell in vitro and explore the underlying mechanisms. Methods Human nasopharyngeal carcinoma cell line CNE-1 was cultured in vitro, and histone H3K27me3/2 demethylation was specifically blocked by histone H3K27me3/2 demethylase inhibitor GSK-J4. The cells were incubated with 0.25,0.5,1.0,2.0,4.0 mmol/L GSK-J4 as the experimental groups, while DMSO was applied as control group. Immunofluorescence assay and flow cytometry were used to analyze the expression of intracellular histone H3K27me3. Real-time quantitative PCR was applied to detect the expression of cyclinD1 and Ki-67 mRNA in cells. Cell counting kit-8 (CCK-8) was used to evaluate cell proliferation. The cloning of CNE-1 cells was observed by colony formation assay. Flow cytometry was also used to detect cell cycle distribution. Results The expression level of histone H3K27me3 in the experimental group was significantly higher than that in the control group (P＜0.05); cyclinD1 and Ki-67 mRNA expression levels in the experimental groups were down-regulated compared with the control group (P＜0.05); The cell viability of CNE-1 cells decreased gradually with the increase of GSK-J4 concentration. The cell proliferation and colony formation in the experimental group were significantly decreased than those in the control group (P＜0.05); cell cycle was blocked in G₀/G₁ phase, the percentage of cells in G₀/G₁ phase was increased and the S phase decreased in the experimental group(P＜0.05). Conclusions Up-regulation of methylation of histone H3K27 in CNE-1 cells induces cell cycle arrest and inhibits cell proliferation. The mechanism may be related to down-regulation of cyclinD1 and Ki-67 mRNA levels.

Effect of Helicobacter pylori isolated from the high incidence area of gastric cancer on the proteome of gastric epithelial cell line GES1

WEI Si-si, DENG Xiao-qing, WANG Xian, XUE Yong-xian, HUANG Yong-sheng, ZHAO Lian-mei, SHAN Bao-en

2020, 40(12): 1619-1625.

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Objective To investigate the effect of Helicobacter pylori-400 that was isolated from high incidence area of gastric cancer on the proteome of gastric epithelial cell line GES1. Methods The gastric mucosa of patients with positive C-13 breath test was sampled with gastroscope, and H.pylori was isolated. GES1 was co-cultured with H.pylori-400 in the ratio of 1∶50, cellular RNA was extracted,and the mRNA expressions of IL-8, IL-1β and TNF-α were detected by RT-qPCR. Cellular proteins were extracted and analyzed by HPLC-MS, lable-free was used for quantitative analysis. The differentially expressed proteins were selected for enrichment analysis of GO and KEGG, and the hub genes were screened out for further analysis. Results H.pylori-400 promoted mRNA expres- sion of IL-8, IL-1β and TNF-α of gastric epithelial cells. HPLC-MS showed that 373 proteins molecules changed(|Fold change|≥2) after GES1 co-cultured with H.pylori-400, among them, 143 proteins molecules decreased and 230 protein molecules increased. GO and KEGG enrichment analysis showed that H.pylori-400 regulated the secretion of inflammatory factors by regulating cell cycle, T cell immune activity and p53 pathway, which may lead to tumor genesis. Conclusions H.pylori-400 isolated from the high incidence area of gastric cancer can promote the expression of inflammatory factors and promote the tumor genesis by affecting the proteome of GES1 cells.

CD151 promotes the proliferation and invasion of colorectal cancer cell line HT29

LIU Xue-gang, LIU Yan-cai, WU Chun-ping, LI Jing-guang, ZHAO Ling-ling, ZHANG Hao, ZHANG Zhen-ya

2020, 40(12): 1626-1630.

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Objective To study the effect of CD151 on proliferation and invasion of colorectal cancer cell line HT29 and the correlated mechanism. Methods The cells were divided into HT29 cell group and CD151-HT29 cell group. The expression of CD151 was detected by RT-qPCR; the protein expression of CD151, LRG-1, LGR-5 and β-catenin was detected by Western blot. The proliferation and invasiveness of HT29 and CD151-HT29 cells were observed by MTS proliferation, cloning and Transwell chamber assay. Results The expression of CD151 in CD151-HT29 cells was significantly lower than that in HT29 cells (P＜ 0.05); the proliferation and invasion ability of CD151-HT29 cells were significantly less than HT29 cells (P＜ 0.05). The protein expression of LRG-1, LGR-5 and β-catenin in CD151-HT29 cells was significantly lower than that in HT29 cells. Conclusions CD151 can promote the proliferation and invasion of colorectal cancer.

Resveratrol alleviates inflammatory response and neuron apoptosis in rats with traumatic brain injury

JIAN Yu, DAI Ling-yun, WU Feng-xue

2020, 40(12): 1631-1635.

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Objective To explore effects of resveratrol (RV) on inflammatory response and neuron apoptosis in rats with traumatic brain injury (TBI). Methods The rats were divided into control group (control), model group (constructing TBI rat model by fluid-percussion method), low, medium and high-dose RV groups with 8 animals in each. The changes of spatial learning and memory ability, hippocampal neuronal morphology, neurocyte apoptosis, inflammatory factors level and the presence of apoptosis-related proteins in each group after trauma were observed. Results Compared with control group, motion trajectory and latency of searching safety island were significantly prolonged in TBI group, hippocampal neuron damage was significant, neuron apoptosis rate, expression of caspase-3, Notch1 and Hes1 were significantly increased, and Bcl-2/Bax level was significant decreased (P＜0.05).Compared with TBI group, RV could shorten rat motion trajectory with dose-dependence, latency of searching safety island, alleviateneuron damage in hippocampus, down-regulate neuron apoptosis rate, expression of caspase-3, Notch1 and Hes1, and up-regulate Bcl-2/Bax level. Conclusions RV can effectively alleviate neuron damage and inflammatory response of TBI rats, and inhibit neuron apoptosis, which may be related to the down-regulating of Notch and Hes1 expression.

Correlation between GA/HbA1c ratio and NAFLD complications in patients with type 2 diabetes mellitus

LU Ya-nan, LIU Li-jun, LI Wei

2020, 40(12): 1636-1639.

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Objective To study the relationship between glycated albumin (GA), glycated hemoglobin (HbA1c), GA/HbA1c ratio and NAFLD in patients with type 2 diabetes and non-alcoholic fatty liver. Methods A total of 502 patients with type 2 diabetes hospitalized from February to December 2017 were divided into 281 cases of type 2 diabetes and 221 cases of type 2 diabetes complicated with NAFLD based on the presence or absence of NAFLD. The correlation biochemical indexes, GA, HbA1c and GA/HbA1c were compared between the two groups using t test and rank sum test, and the correlation analysis of GA/HbA1c ratio and regression analysis of influencing factors of type 2 diabetes combined with NAFLD were performed. Results GA/HbA1c in T2DM complicated with NAFLD group was higher than that in T2DM group(P＜0.05). GA/HbA1c was positively correlated with GA, CRP and FPG(P＜0.05), and negatively correlated with fasting C-peptide(P＜0.05). Logistic regression analysis showed that GA and GA/HbA1c were risk factors for T2DM complicated with NAFLD(P＜0.05). ROC curve: area under the curve of GA/HbA1c was 0.745, area under the curve of GA was 0.660. Conclusions GA/HbA1c is an independent risk factor for T2DM complicated with NAFLD.

Molecular genetic analysis and clinical consideration of two families with GCK gene mutation

WANG Zhi-xin, ZUO Qing-yao, LI Wei, CHEN Jia, DENG Wei

2020, 40(12): 1640-1644.

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Objective To explore the molecular genetics and clinical characteristics of two cases of maturity-onset diabetes of the young (MODY) type 2 caused by glucokinase (GCK) gene mutation. Methods Two patients who were admitted into Beijing Jishuitan Hospital with suspected diagnosis of MODY from April 2015 to December 2015 were collected and analyzed by their clinical data. GCK gene sequencing was carried out for the two patients and their family members to find the cause of their disease. Results A new GCK heterozygous mutation p.T82P (c.244 A ＞ C) and a reported GCK heterozygous mutation p.V412M (c.1234 G ＞ A) were found in the two families. In the aspect of clinical manifestations, in addition to stable hyperglycemia, the 3 GCK gene mutation carriers in the two families showed metabolic syndrome of varying degrees. Conclusions GCK gene mutation p.T82P may be the cause of MODY2. The clinical manifestations of GCK gene mutation carriers are complex, and they need to be individualized and managed in treatment and prognosis.

Impact of glycosylation and length of RBD of SARS-CoV-2 S protein on the immunogenicity of RBD protein vaccines

ZHANG Ting, WANG Zhi-rong, XU Xue-mei

2020, 40(12): 1645-1650.

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Objective To analyze the impact of deglycosylation and length of RBD of SARS-CoV-2 S protein on the immunogenicity. Methods Based on the RBD of the SARS-CoV-2 S protein, three N-glycosylated residues (N331, N343, N360) in the 220 amino acid RBD (aa.331-550) were respectively mutated, and trimerization domains were fused at the C-terminus of resulted peptides. The resulted deglycosylated trimer proteins (RBDT-N1, RBDT-N2, RBDT-N3) were expressed in baculovirus-insect cell expression system. The wild-type control of deglycosylated proteins (RBDT) and RBDST (aa.319-591) with a length of 273 amino acids were also constructed. The expression levels were analyzed by Western blot. Proteins were purified by affinity chromatography. Mice were immunized, and the sera were subjected to analysis of RBD-specific IgG and neutralizing antibodies against SARS-CoV-2 pseudovirus. Results Deglycosylation increased the expression level of RBD trimers in insect cells. RBDT and three deglycosylated proteins (RBDT-N1, RBDT-N2, RBDT-N3) induced similar level of RBD-specific IgG and SARS-CoV-2 pseudovirus neutralization titers. RBDST induced high titers of RBD-specific IgG and neutralizing antibodies, which were both significantly higher than that induced by RBDT (P＜0.05,P＜0.01). Conclusions The results suggest that removing the N-glycosylation residues of RBD and extending the RBD flanking sequence are beneficial to increase the expression and immunogenicity of the RBD protein vaccine. The research provides a useful reference for the development strategy of RBD-based SARS-CoV-2 vaccines.

Clinical and genetic manifestation of pheochromocytoma patients with RET mutation

MA Xiao-sen, WANG Fen, CUI Yun-ying, ZHOU Ting, CHEN Shi, LU Lin, TONG An-li, LI Yu-xiu

2020, 40(12): 1651-1655.

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Objective To explore clinical and genetic manifestation of pheochromocytoma patients with RET gene mutation. Methods Clinical data, laboratory examination results and RET gene mutations of 23 pheochromocytoma patients with RET mutation treated in Peking Union Medical College Hospital from 2013 to 2019 were retrospectively analyzed. Results The diagnosis age of pheochromocytoma in 23 patients was 32±10 years. In 22 patients with multiple endocrine neoplasia (MEN) 2A, mutations were clustered in exon 16 (18 cases), especially in codon 634 (16 cases), followed by exon 10 and 14, and one patient with MEN2B had M918T in exon 16. Among the 23 patients, 9 had paroxysmal hypertension, 5 had sustained hypertension, 3 were normotensive, and 6 had episodic palpitations but their blood pressures were not measured during the attacks. 24 h urinary catecholamine excretion was as following: norepinephrine (NE): 65.8 (36.9,235.9) μg/24 h, Epinephrine (E): 5.4 (2.8, 37.2) μg/24 h and Dopamine (DA): 277 (198, 297) μg/24 h. 15 patients had abnormally increased NE, E or DA, while 8 patients had normal catecholamine excretion. The median diameter of the tumors was 4 (3, 6) cm. Fifteen patients had bilateral pheochromocytoma and 17 had medullary thyroid carcinoma. Conclusions Pheochromocytoma patients with RET mutation are consistent with those reported in western countries in terms of age at diagnosis, tumor size and mutation profile. Most patients have paroxysmal hypertension or normal pressure, and some of them have normal urinary catecholamine excretion, which are potential risk factors of missed diagnosis.

MST1 regulates hepatic gluconeogenesis by promoting PEPCK expression in mice

XIE Xiang-hong, GENG Chao, ZHAO Wei, LI Chun-mei, ZHANG Wei-hong, YANG Jia-hui, LIU Xiao-jun

2020, 40(12): 1656-1660.

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Objective To investigate the role of mammalian sterile line 20-like kinas 1(MST1) and its regulatory mechanism in hepatic gluconeogenesis of mouse. Methods The mRNA expression of MST1 in the liver of db/db mice and db/m mice was detected by RT-qPCR. MST1 was overexpressed with adenovirus to detect glucose output capacity in mouse primary hepatocytes. Luciferase reporter assay was adopted to detect the effect of MST1 on phosphoenolpyruvate carboxykinase (PEPCK) promoter activity in HepG2 cells. Forkhead transcription factor O1 (FOXO1) was knocked down by interfering adenovirus in primary mouse liver cells to detect the effect of MST1 overexpression on the mRNA levels of PEPCK. Results The mRNA level of MST1 was significantly upregulated in the liver of db/db mice (P＜0.001). MST1 overexpression enhanced glucose output in mouse primary hepatocytes (P＜0.05). In HepG2 cells, MST1 overexpression increased the mRNA of PEPCK (P＜0.001) and the activity of PEPCK promoter (P＜0.01). Furthermore, MST1-induced increase in PEPCK mRNA was abolished when FOXO1 was knocked down by interfering adenovirus. Conclusions MST1 promotes hepatic gluconeogenesis by regulating the mRNA expression of PEPCK dependent on FOXO1.

Antibiotic resistance of Helicobacter pylori:a multicenter prospective analysis

YE Shan-shan, LI Jun-da, ZHOU Ying-sheng, LIU Lu, WU Jian-wei, LYU Zhi-wu, LIU Jin-tao

2020, 40(12): 1661-1665.

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Objective To investigate the infection of Helicobacter pylori (Hp) and its resistance to six kinds of antibiotics in Shenzhen. Methods Urease test and Hp cultivation were performed in 5 080 patients with gastrointestinal discomfort in three hospitals in Shenzhen, and antibiotic sensitivity test of agar dilution was performed. Results Among the 5 080 patients, a total of 3 203 patients were Hp positive, with a positive rate of 63.05%. The resistance rate of 3 203 Hp strains to antibiotics was metronidazole (MNZ)(99.6%),amoxicillin(AMX)(30.5%),clarithromycin(CAM)(10.6%), doxycycline (DOX) (0.3%), furazolidone(FR) (0.2%), and levofloxacin(LVX) (0.1%). The rates of total sensitivity to Hp was 0.18%, single drug resistance, double and multiple drug resistance were 62.06%, 33.94% and 3.81%, respectively. MNZ and AMX had the highest double drug resistance (26.69%), while MNZ, CAM and AMX had the highest triple drug resistance (3.68%). The age ≤40 years seems to be a factor for single antibiotic resistance, while the age ＞40 years is a risk factor for double antibiotic resistance of Hp strain. Gender is an influence factor of Hp strain on CAM and single and double antibiotic resistance. Conclusions Hp has a high infection rate and high resistance to MNZ, followed by AMX and CAM.

Effect of astragaloside on renal function and serum IL-1β and IL-17 in mice with mesangial proliferative glomerulonephritis

LIANG Wen-lin, LI Jun, JIN Guang-ming, YAN Jin-sheng, YAO Yuan

2020, 40(12): 1666-1670.

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Objective To investigate the effects of astragaloside IV(ASIV) on renal function of mice with mesangial proliferative glomerulonephritis (MsPGN) and the regulation of serum IL-1β and IL-17. Methods Thirty-two ICR clean male mice were randomly divided into crotrol group, model group, Tripterygium wilfordii polyglycoside tablet group (positive drug group) and astragaloside IV (ASIV intervention) group with 8 mice in each group. MsPGN model was established by routine method. After 12 weeks of treatment, the pathological changes of kidney tissue were microscopied. Routine biochemical method was used to detect 24 h urinary protein (24 hUP) in mice 1 day before treatment, 4, 8 and 12 weeks after treatment. Detection of serum cystatin C(Cys C) expression, renal tissue homogenate and serum IL-1 β and IL-17 by ELISA. The beta-N-acetylglucosaminidase (NAG) was measured by colorimetry. Results Compared with the control group, mesangial cells and mesangial matrix proliferated in model group mice. After treatment with ASIV and Tripterygium wilfordii polyglycoside tablets, the kidney lesions and mesangial cell and mesangial matrix proliferation in mice were alleviated. Compared with the control group, the expression levels of 24 hUP, NAG, Cys C, IL-1β and IL-17 in kidney tissue and serum of the model group were significantly increased (P＜0.05). After treatment, the expression levels of 24 hUP, NAG, Cys C, IL-1β and IL-17 in ASIV group and Tripterygium wilfordii polyglycoside tablet group were dose-dependent, and significantly lower than those in model group (P＜0.05). Conclusions Astragaloside Ⅳ regulates renal function, inhibits proliferation of mesangial cells and the increase of extracellular matrix, and alleviates renal injury, which is potentially related to the inhibition of inflammatory reaction of renal tissue by ASIV.

Alleviation of skin lesions and bone pain in patients with SAPHO after tonsillectomy

WANG Yi, XIANG Yi-rong, LI Chen, ZHANG Wen, GAO Zhi-qiang

2020, 40(12): 1671-1676.

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Objective To evaluate the clinical efficacy of tonsillectomy on skin lesions and bone pain in patients with synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO). Methods Patients with SAPHO who were refractory to conservative treatment and then received tonsillectomy were recruited. The skin lesions were evaluated using palmoplantar pustulosis area and severity index (PPPASI) scoring. The pain was evaluated by the visual analog score (VAS). The scores of PPPASI and VAS at various follow-ups were recorded. Results Forty-four patients (36 women and 8 men) with a median age of 37.3 years were enrolled. One month after tonsillectomy, skin lesions and bone pain disappeared in 10% and 28% respectively. The disappearance rates 12-month post-op, were 62% and 77% respectively. Conclusions Tonsillectomy exhibits inhibition to skin lesions and bone pain in the patients with SAPHO. Tonsillectomy is a potential alternative treatment for the refractory cases.

Clinical diagnosis and treatment of bitaleral acoustic neurofibromatosis type 2: a retrospective analysis of 4 patients

YANG Chang-li, TU Guo-long, XIA Ying

2020, 40(12): 1677-1680.

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Objective To investigate the diagnosis and treatment of neurofibromatosis type2(NF2). Methods The clinical manifestations, magnetic resonance imaging(MRI) findings, and treatment of 4 patients with surgically and pathologically-confirmed NF2-associated bilateral acoustic neufibroma were retrospectively analyzed,along with literature review. Results Bilateral acoustic neuroma was the mainly clinical manifestation in these four NF2 patients,although unilateral acoustic neuroma and schwannoma have also been described in literature.Microsurgery remains the mainstream treatment for NF2. Conclusions NF2 has unique clinical manifestations and MRI findings. It is mainly diagnosed by MRI and treated by surgery.However, the timing of surgery should be individualized and pay attention to the protection of the hearing at one side.

Analysis on diagnosis and treatment of inpatients with acute coronary syndrome in Xicheng district of Beijing

YANG Ling, DU Xue-ping

2020, 40(12): 1681-1685.

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Objective To analyze the diagnosis and treatment of acute coronary syndrome (ACS) inpatients in Xicheng district, Beijing, and put forward suggestions for coronary heart disease secondary prevention/cardiac rehabilitation. Methods Cluster sampling was carried out. ACS inpatients were screened by searching the home page of medical records of Xicheng district, Beijing between 2012.1.1—2016.12.31 based on the International Classification of Diseases (ICD)-10 codes from Beijing Municipal Health Information Center. Results The average onset age of ACS inpatients was 69 years old, and male patients accounted for 59.83% to 62.68%. Onset age ＞60 years accounted for about 70%; The percentage of 60＜onset age≤75 years old increased gradually. Non-st-segment elevation acute coronary syndrome (NSTE-ACS) including unstable angina(UA) and acute non-ST segment elevation myocardial(NSTEMI),accounted for 83.21% to 86.89% of the total ACS hospitalized patients.The percentage of hospitalized patients with unstable angina(UA) was more than 72.00% over the years. Coronary angiography was performed in 51.36% to 56.42% ACS inpatients. Percutaneous coronary intervention(PCI) treatment accounted for 9 342 person-time, accounting for 27.83 to 32.01% of the total ACS hospitalization. 26.32% to 30.28% of the ACS inpatients were performed Coronary stent implantation. PCI was performed in 48.21% to 54.89% of STEMI inpatients,30.90% to 33.56% of NSTEMI inpatients, and 22.33% to 27.14% of UA inpatients. Conclusions The main incidence of ACS in Xicheng district is NSTE-ACS. However, the proportion of patients receiving interventional therapy and revastigectomy is low. It is urgent to strengthen the prevention of cardiovascular disease and cardiac rehabilitation treatment, especially in the age population of 60-75.

Comparison of chest CT changes in patients with COVID-19 and patients on maintenance hemodialysis

ZHAO Bin, LIU Jing, LIU Yin, YANG Tao, WANG Yu-zhu

2020, 40(12): 1686-1690.

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Objective To compare the features of chest CT scans in patients with COVID-19 infection and in patient on maintenance hemodialysis (MHD), so as to provide a reference for clinical diagnosis and differential diagnosis. Methods The complete clinical data and chest CT findings of 35 patients with COVID-19 and 60 patients on MHD who had been admitted to Beijing Haidian Hospital from February to March 2020 were collected, their imaging features and clinical characteristics were analyzed and compared. Results A total of 95 patients were included, aged from 18 to 80 years old. Among the 35 patients with COVID-19, 32 cases (91%) had lesions mainly distributed in the lung field, 25 cases (71%) had ground glass opacities as the major manifestation, 22 cases (63%) were associated with interlobular septal thickening, 28 cases (80%) were complicated with intravascular thickening, and 11 cases (31%) had bronchial inflation. Among the 60 patients on MHD, 31 cases (41%) had lesions mainly distributed in the centers of the bilateral lung fields, 42 cases (70%) had ground glass opacities, 37 cases (62%) interlobular septal thickening, including 4 complicated with peribronchial cuff- ing(7%), 41 cases (68%) had enlarged cardiac shadow, including 14 (23%) complicated with pleural effusion, and 27 cases (45%) had widened pulmonary artery. Conclusions Both patients with COVID-19 and those on MHD were found with ground glass opacities complicated with interlobular septal thickening on chest CT, but patients on MHD showed obvious changes such as enlarged cardiac shadow complicated with widened pulmonary artery. Therefore, the chest imaging features from the two types of patients can be used to provide a solid basis for clinical and differential diagnosis.

Halcyon analyzed target margin in 142 patients with lung cancer treated by conventional segmentation therapy

XU Hao-ran, SUN Xian-song, WANG Xin-hai, HU Ke, QIU Jie, ZHANG Fu-quan

2020, 40(12): 1691-1694.

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Objective To analyze the conventional segmental positioning error of lung cancer with Halcyon and the outspread boundary of the target area, so as to improve the precision and efficacy of radiotherapy in patients with lung cancer with Halcyon. Methods Totally 142 patients from May 2019 to August 2020 in the radiotherapy department of Peking Union Medical College Hospital were selected in this study and 3 192 registration images were collected for data analysis of the whole course of treatment, and the errors of elevation direction (VRT), inlet and outlet direction (LNG) and left-right direction (LAT) were calculated. The outer boundary formula of target area=2.5∑+0.7 and combined with the ICRU50 and ICRU62 report analysis results. Results By SPSS 21.0 statistical analysis, the positioning errors of the three directions were as follows: VRT(0.07±1.59)mm, LNG(-0.15±4.40)mm, and LAT (0.08±3.50)mm. According to the analysis of ICRU50 and ICRU62 reports, the target margin is VRT=3.69 mm,LNG=6.60 mm and LAT=5.04 mm. Conclusions With conventional segmental treatment model, the boundary of the exotherm of the lung cancer patients in the target area of the Halcyon medical electron linac was VRT=3.69 mm, LNG=6.60 mm and LAT=5.04 mm, which provided the basis for the exotherm of the clinical target margin.

Research progress of fibroblast growth factor homologous factor 1 in the pathogenesis of arrhythmia

QIN Tao, LI Qing, LI Ju-xiang

2020, 40(12): 1697-1700.

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Fibroblast growth factor homologous factor 1 (FHF1) is an intracellular signaling protein, a non-specific fibroblast growth factor that does not bind to fibroblast growth factor receptors. FHF1 combines with the C-terminus of cardiac voltage-gated sodium ion channels to regulate Na⁺current, which in turn affects the action potential of myocardial cells and results in arrhythmias with a higher frequence.

Research progress of peripheral blood free DNA in preeclampsia pregnancy

ZHOU Jia-yi, WU Xun-wei, DAI Li-juan, ZHAO Gui-li, YU Bo-lan

2020, 40(12): 1701-1705.

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Pregnancy-induced hypertension, especially preeclampsia (PE), is one of the leading causes of increased maternal and perinatal morbidity and mortality worldwide. And the circulating cell free fetal nucleic acid (cff-DNA) analysis of pregnant women can be used as an early prediction of the occurrence and development of PE. By summarizing and analyzing the correlation between cff-DNA and PE and its possible mechanism, this paper further explained that the occurrence of PE may be related to DNA methylation, and discussed its limitations as a biomarker, so as to provide reference for the effective prediction of preeclampsia.

Biological characteristics and clinical application of leucocyte-and platelet-rich fibrin

SUN Hui-ying, ZHU Chong-yuan, FENG Guo-dong, GAO Zhi-qiang

2020, 40(12): 1706-1710.

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Autologous blood-derived products get more attention as a special kind of biological products. Leucocyte-and platelet-rich fibrin (L-PRF) is the most classic second-generation platelet concentrates of autologous blood-derived products. It has more advantages than the first-generation products like platelet-rich plasma (PRP), because of the more stable fibrin network, higher concentration of cytokines and growth factors, and higher biological effects. Besides, L-PRF is easier to obtain and safer for the body. Now it has been widely used in department of stomatology, orthopedics and plastic surgery. L-PRF has the potential to serve as an ideal material for recovery and construction of soft tissues and bony defect in oncology surgery.

Progress in research on pyroptosis and cardiovascular diseases

ZHU Kun, DAI Ri-lei, ZHU Wen-ting, LI Zhen-yan, CAO Chun-mei

2020, 40(12): 1711-1715.

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Pyroptosis is a kind of programmed cell death mediated by the gasdermin protein, including the classical pathway that depends on caspase-1 and the non-classical pathway that depends on caspase-4, -5, and 11, accompanied by the release of a large number of inflammatory factors. Atherosclerosis, myocardial ischemia, heart failure and other cardiovascular diseases are closely related to inflammatory response. Pyroptosis, as a highly pro-inflammatory cell death, is also widely involved in the occurrence and development of the cardiovascular diseases, and plays an important role in these diseases.

Research progress of tumorigenicity-related proteins

AO Hui-juan, SHI Jia-chen, WANG Jia-min, Ayimuguli ABUDUREYIMU, QIAO Zi-lin, YANG Kun

2020, 40(12): 1716-1720.

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The occurrence and development of tumors include the tumorigenicity of tumor cells in vivo, the growth of xenograft tumors, angiogenesis, tumor migration, invasion and metastasis. Tumorigenicity-related proteins play an important regulatory role during these processes. Research of tumorigenicity-related proteins is of great significance for identifing new targets for tumor treatment and blocking tumor occurrence and development. We reviewed the effects of tumorigenicity-related proteins on cell tumorigenesis, the consequence of protein interactions on tumor migration and invasion, the effects of tumorigenicity-related proteins on cell migration and invasion in vitro, and their relationship with tumor metastasis. This review provides rich information on the regulatory mechanism of tumorigenicity-related proteins in tumor development.

Research progress of different cells derived exosomes in COPD

YANG Yue, BIAN Tao

2020, 40(12): 1721-1726.

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Exosomes are lipid bilayer vesicles secreted by almost all types of cells, which consist of various proteins, DNA, mRNA, miRNA and LncRNA. They are an important medium for communication between cells and participate in various physiological and pathological processes. In chronic obstructive pulmonary disease (COPD), bronchial epithelial cells, macrophages, neutrophils and other cells can participate in COPD airway remodeling and emphysema by secreting exosomes. Moreover, mesenchymal stem cells and adipose stem cell-derived exosomes play an important role in the treatment of COPD.

Exploration of standardized inquiry training software “Yask”

TAN You-hai, JIN Zhao-heng, ZHANG Rui, WANG Jing, SHEN Peng-cheng

2020, 40(12): 1727-1731.

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Inquiry is an essential component of diagnostics and one of the essential skills that a clinician required. In order to improve the efficiency of learning inquiry, communication skills, clinical consultation skills, it is worth developing a training model that stimulates inquiry with standardized computer virtualization software. Through the investigation in the early stage with medical students, our team has developed an inquiry simulation software “Yask” with choosing form and made some explorations of reasonable evaluation of inquiry results.

Practice and re-understanding of American medical education system in China

LIU Ai-ming, ZHAO Chan-juan, LING Yan-wu, YANG Ju-lin

2020, 40(12): 1732-1735.

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The author team attended a group which visited University of Nebraska Medical Center and experienced their medical education system in 2016, sponsored by China Scholarship Council. Some education reformations and trials were carried out in the authors’ affiliations after the program finished. In this work, an analysis of the differences in medical education of the USA and of China was made, combining the published perspectives and our own experiences. The critical comments raised in this work may contribute to the remodeling of our medical education system and teaching mode.

Teaching reform of diagnostics guided by multivariate integrated mode based on the Excellent Doctor Education and Training Program

ZHANG Jun, QIAO Li-fen, WEI Shuang, CHEN Xi, HUANG Jin, MA De-lin, SHI Wen-jing, XU Xi-zhen

2020, 40(12): 1736-1739.

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Different teaching methods were utilized according to various teaching contents. The multivariate integrated teaching system (LBL,PBL,CBL,TBL,RBL,Sandwich,SP,microteaching,scenario simulation,role playing method,multimedia network and so on) for the learning of diagnostics had been constructed as an activity of “Excellent Doctor Education and Training Program”. Teaching reform of diagnostics guided by multivariate integrated mode improved students' learning, independent thinking and capacity of solving problems. Comprehensive capacity of teachers had also been enhanced. The reform of education and training mode of five-year clinical medicine students had been promoted which facilitated learning of diagnostics.

Application of oral examination in self-evaluation and evaluation of senior anesthesia resident

YU Chun-hua, LI Xu, ZHANG Yue-lun, QUAN Xiang, RUAN Xia, TAN Gang, HUANG Yu-guang

2020, 40(12): 1740-1743.

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Objective To assess the capability of senior residents in clinical competency, and to compare the difference between examiner grading and examinee grading. Methods 44 third year residents attended the oral examination in 2018 and 2019. The oral exam lasted 20 minutes covering questions from preoperative evaluation, intraoperative management, and to postoperative management. Two examiners participated in the oral exam. Results The examiners gave the grading of 3.54±0.72 for majority of the time, and gave the grading of 3.34±0.94 for minority of the time. The residents showed the best ability in oral communication skills appropriate for level in residency, and showed the poorest ability in being able to adapt to changes in the clinical situation 3.28±0.77 and understanding advantages and disadvantages of alternative management strategies 3.29±0.73. The examinee gave the grading of 3.17±0.63 for majority of the time, and gave the grading of 3.09±1.12 for minority of the time. The residents evaluated themselves the highest score in communicates information logically and effectively 3.34±0.81, and evaluated themselves the lowest score in being able to adapt to changes in the clinical situation 3.07±0.70 and understanding advantages and disadvantages of alternative management strategies 2.84±0.75. Most of the residents (73%) reached the score equal or more than 3. Examinees intended to underrate themselves significantly(P＜0.05). Conclusions Most of the third year residents showed appropriate clinical competence acquired for this stage. Residents in anesthesia should practice more in understanding advantages and disadvantages of alternative management strategies and in being able to adapt to changes in the clinical situation. To improve the clinical competence, practice oral examinations should be instituted in the resident training programs in China.

Current status of virtual reality and augmented reality-based training tools in ophthalmology teaching

ZOU Xuan, SUI Rui-fang

2020, 40(12): 1744-1748.

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The virtual reality (VR) or augmented reality (AR)-based simulators have been used to learn ocular anatomy, ophthalmic examinations and surgery procedures. Students can easily understand complex concepts and receive knowledge transfered through observation, imitation and participation. Most researches showed that these new tools improved learning efficiency, assist developing skills and improved the safety of surgical practice in early careerhood, shedding light on reformation in ophthalmology education and teaching.

Preliminary study on application of blend teaching based on “rain classroom” in practice anatomy of human anatomy class

HE Hong-yun, DENG Yi-hao

2020, 40(12): 1749-1752.

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In order to explore the learning outcome of hybrid mode in human anatomy experiment class. The “rain class” tool is used to organize the teaching through the modes of pre-learning before class, explaining in class and summarizing after class. The results show that the mixed teaching mode in the human anatomy experiment courses can stimulate students' interest in learning, build students' autonomous learning capacity, and improve the learning outcome.

Design and exploration of core curricula in graduates for academic degree of clinical medicine

CHANG Xing, JIA Xue-yan, ZHU Dong-wei, LUO Lin-zhi, QIU Jie, LI Li-min

2020, 40(12): 1753-1756.

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Peking Union Medical College Hospital has explored and designed the core curricula of graduates' clinical medicine education. Through the introduction and analysis of the goal, contents and course outline of core curricula, the authors hope to strengthen the reform of the graduates' curricula and improve the innovation capacity of learners.

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