Table of Content

    05 September 2018, Volume 38 Issue 9
    Chrysin attenuates secondary cardiomyocyte injury induced by mechanical trauma in rats
    2018, 38(9):  1217-1223. 
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    Objective We are aimed at observing the protective effect of chrysin has on the mechanical traumatic rat heart, and explore the mechanism both in vivo and in vitro. Methods Rats were randomly divided into control group, trauma group without treatment and trauma group with injection of chrysin or solvent DMSO, there are 5 rats in each group. Recorded the changes of the left ventricular diastolic pressure. By TUNNEL staining, we assessed the apoptosis degree of cardiomyocytes. MTT assay was used to evaluate theproliferation of cells. ELISA test was administered to identify the TNF-α level. DCFH-DA was used to estimate the intracellular generation of ROS. We used confocal laser scanning microscope photoed fluorescent images to observe the cardiomyocytes to determine the changes of intracellular Ca2+ . Results Compared with control,in trauma group,+dP/dTmax, MAP, -dP/dTmax and LVDP were significantly decreased(P<0.01),the apoptosis index apparently increased(P<0.01);The survival rate of inflammatory cells induced by TNF-α was lower(P<0.01);And There is a significant increase of TNF-α and ROS level.(P<0.01).Compared with trauma group,in chrysin group,+dP/dTmax, MAP, -dP/dTmax and LVDP were significantly increased(P<0.01),the apoptosis index apparently decreased(P<0.01);The survival rate of inflammatory cells induced by TNF-α was higher(P<0.01);And There is a significant decrease of TNF-α and ROS level.(P<0.01). Conclusions Chrysin alleviates MT induced the excessive release of TNF-α,ROS and intracellular calcium overload which will reduce the apoptosis of myocardial cells and protect the heart.
    Tauroursodeoxycholic acid (TUDCA)alleviates hepatocyte apoptosis of type 2 diabetes mellitus mice
    2018, 38(9):  1224-1230. 
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    Objective To observe the effect of tauroursodeoxycholic acid (TUDCA) on hepatocytes apoptosisofspontaneoustype 2 diabetes mellitusdb/db mice and to explore its mechanism. Methods db/dband db/m (lean)mice were randomly divided into control groupsandTUDCA-treatedgroups.TUDCA 500mg/kg/day was given by gavage for 2 weeks in TUDCA-treated groups. The levels of fasting plasma glucose (FPG) and fasting insulinin serum and the levels of malondialdehyde (MDA), reactive oxygen species (ROS) and superoxide dismutase (SOD) in liver tissue were detected.Lipid deposition in liver tissue was detected by oil red O staining. Hepatocytes apoptosis in liver tissue was examined by TUNEL method. The transcription and expression levels of C-JUN and XBP-1 in liver tissue were examined by real-time PCR and western blotting method. The morphology and ultrastructure changes of liver tissue were observed by light microscope and transmission electron microscope. ResultCompared with lean control group, the levelsof FPG, aminotransferase, MDA and ROS were increased ; theexpression levels of C-JUN and XBP-1 were upregulated; lipid droplets and apoptosis of hepatocyteswere significantly increased in db/db control group(p<0.05). Compared withdb/db control group, the levels FPG, aminotransferase, MDA and ROS were decreased; theexpression levels of C-JUN and XBP-1 were downregulated; lipid droplets and apoptosis of hepatocyteswere significantly decreasedin db/dbTUDCA-treated group(p<0.05).ConclusionTUDCA can alleviatehepatic damage of type 2 diabetes mellitus db/db mice by inhibiting hepatocytesapoptosis. Its mechanism may be related to inhibiting oxidative stress reaction, and downregulatingtheexpression of C-JUN and XBP-1 gene.
    Effect of hypothalamus pituitary adrenal axis disorder on hippocampal formation in rats with anxious depression
    2018, 38(9):  1231-1238. 
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    Objective To study the effect of HPA axis disorder on the hippocampal formation in rats with anxious depression and to explore its potential pathogenesis. Methods Rats were randomly divided into control group, vehicle group, anxiety group, depression group and anxious depression group, 12 rats in each group. Anxious depression rats were intervened by chronic restraint stress combined with corticosterone injection for continuous 21 d. Then, elevated plus maze (EPM), open field test (OFT), forced swimming test (FST) were used to evaluate the anxious and depression like behavior in rats, HE staining to check pathological changes of the HPA axis tissue and hippocampus. The plasma levels of CRH, ACTH and CORT of rats were detected by ELISA, and the expression of GR in hippocampus was detected by Western blot. Results Compared with control group and depression group, there were significant differences (P<0.01 or P<0.05) in OE% and OT% at EPM and independent activity frequency during OFT, which was similar to anxious depression group. Compared with control group and anxious group, the immobility time in FST was increased significantly (P<0.01). HE staining showed that all tissues of HPA axis were damaged in different degrees, and the hippocampal neurons were swollen and vacuolated. Conclusions Ansious depression rats had significant anxious and depressive behaviors, which pathogenesis may be closely related to the HPA axis disorder and hippocampus region damage.
    Changes in submucosal plexus neurons of colon in a rat model of irritable bowel syndrome with constipation
    2018, 38(9):  1239-1243. 
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    Objective To investigate the changes of excitatory and inhibitory neurons in submucosal plexus (SMP) of colon in a rat model of IBS-C. Methods The rat model of IBS-C was established by intragastric perfusion with icy water. Whole-thickness colon specimens were collected to prepare submucosal layer with intact SMP. Multiple immunofluorescence staining technique was used for detecting the total numbers of SMP neurons and ganglia, the numbers of the SMP neurons expressing specific neurochemical markers (ChAT, VIP, NOS), and the activation status of SMP neurons. Results Compared with control group, the intestinal transmission rate of model rats was slower, and the number of fecal granules and water content of feces were less than that of controls. In the colon SMP of rat with IBS-C( n=7), the total number of SMP neurons/HPF and the total number of activated neuron/HPF increased significantly(P<0.05); the percentages of activated ChAT-IR neurons and activated VIP-IR neurons decreased significantly, and the percentage of activated NOS-IR neurons increased significantly. Conclusions The changes of colonic SMP may play an important role in the pathogenesis of IBS-C.
    Human bone marrow mesenchymal stem cells induce epithelial-mesenchymal transition in breast cancer cell line MCF-7
    2018, 38(9):  1244-1250. 
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    Objective To explore whether epithelial-mesenchymal transition(EMT) is affected after the human bone marrow mesenchymal stem cells (hBMSCs) co-cultured with MCF-7 breast cancer cells. Study the effect of paracrine factors on proliferation and migration in MCF7 cells. Methods hBMSCs was isolated successfully in vitro.Co-cultured hBMSCs with breast cancer cell line MCF-7 by transwell chamber, then observed the morphological changes of MCF-7 cells. The expression levels of E-cadherin, vimentin,α-SMA and β-catenin were detected by real-time quantitative PCR,Western blot and immunofluorescence. Collected conditional-culture medium from co-culture system and acted on MCF7 cells, Western blot analysis tested EMT markers of MCF7 cells,CCK8 assay deteced cell growth activity, flow cytometry tested cell cycle, transwell investigated invasion and metastasis of MCF7 cells. Results After co-cultured with hBMSCs,MCF7 cells showed incresed EMT ability(P<0.05). Stimulated with conditional-medium from the co-cultured system,the EMT characteristics and proliferation, migration ability of MCF7 cells were enhanced(P<0.01). Conclusion hBMSCs could induce EMT of breast cancer cells and promote the prolifertion,migration and invasion capacity of breast cancer cells by paracrine signal.
    Endothelial to mesenchymal transition participates in doxorubicin induced rat myocardial fibrosis
    2018, 38(9):  1251-1257. 
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    Objective To study the of mechanism of adriamycin induced myocardial fibrosis .Methods Construct rat model of doxorubicin induced myocardial fibrosis. Detect the myocardial pathological changes with HE and Masson staining, and detect the expression level of fibrosis related gene Col1α, Col3α, TGF-β1 with RT-qPCR and immunohistochemistry. The immunofluorescence technique was used to detect the expression of the marker of vascular endothelial cell (vWF) and mesenchymal cell (α-SMA). Results Enlargement of ventricular cavity, thinning of heart wall, widening of myocardial fiber space, myocardial dissolving and fibrosis, myocardial vascular endothelial injury and permeability increase happened in rats with intraperitoneal injection of adriamycin. With the prolonged action of adriamycin, the expression of myocardial fibrosis factors and fibrosis related factors Col1α、Col3α、TGF-β1 increased, endothelial cell transformation happened in cardiac vascular endothelial cells. Conclusion Adriamycin can induce irreversible myocardial fibrosis in rats, and endothelium transformation is involved in the formation of doxorubicin induced myocardial fibrosis.
    Isoflurane inhibits endoplasmic reticulum stress apoptosis induced by hypoxia/reoxygenation in HK-2 cell line
    2018, 38(9):  1258-1262. 
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    Objective to investigate the effects of isoflurane treatment on hypoxia/reoxygenation-induced endoplasmic reticulum stress (ERS) and apoptosis in HK-2. Methods After treatment of hypoxia/reoxygenation in HK-2, 2.56% isoflurane was added and incubated for 1, 4 and 8h. Then the lactate dehydrogenase (LDH) and MTT were measured for detecting the hypoxia/reoxygenation-induced injury and cell viability in HK-2 cells. Flow cytometry was performedto detect apoptosis. RT-qPCR and semi-quantitative Western blot were employed for analyzing hallmarks of endoplasmic reticulum stress, GRP78, CHOP and caspase-12. Results After 4 and 8-hour co-incubation with 2.56% isoflurane, LDH is lower and MTT is higher in treated groups, compared with mock group (P<0.05), indicating the promoting effect of isoflurane treatment on cell survival. 1-hour co-incubation with 2.56% isoflurane presented undetectable effect on cell survival. Consistently, Annexin V/PI double staining results present that, the apoptotic rate in 4h-treated and 8h-treated group is (12.1±1.3%)和(7.1±1.1)%, which are significantly lower than mock group ((24.2±4.6)% and(13.3±3.1)%, P<0.05). GRP78 and caspase-12, but not CHOP were upregulated in treated cells compared to untreated cells. After isoflurane treatment, caspase-12 activity was downregulated. Conclusion Isoflurane treatment inhibited ER stress-induced apoptosis in hypoxia/reoxygenation model cells by downregulating caspase-12 activity.
    3D bioprinting hydrogel structure lamella of rabbit’s 1ung fibroblasts
    2018, 38(9):  1263-1267. 
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    Objective To construct three dimensional(3D) structure lamella containing rabbit’s 1ung fibroblasts/alginate/gelatin blend using 3D bioprinting technique. Methods Rabbit’s 1ung fibroblasts were extracted from lung tissue pieces of newborn rabbit using collagenase digestion combined with tissue pieces culture method. Alginate and gelatin were mixed to form hydrosol,and rabbit’s 1ung fibroblasts were added into the hydroso1.A 3D bioprinting system was used to construct 3D printed like-lung structures using rabbit’s 1ung fibroblasts-alginate-gelatin blend.The like-lung hydrogel structures were cultured, and the cells’ survival rate was detected by live/dead cells double fluorescence staining. Results The 3D structures with the grid hydrogel composed of multilayer staggered cylindrical microfilament were obtained. The size of the structure was about 9 mm×9 mm×1.2 mm, and pore size was about 600 μm×600 μm. The results of live/dead cells fluorescence staining showed that the 1ung fibroblasts’ survival rate was 84%±3% after printing.Conclusions 3D bioprinting of 1ung fibroblasts is feasible,which provides a new way to construct like-lung tissue engineering.
    Effects of SFRP5 on glucose metabolism in mouse hepatocellular carcinoma cell line Hepa1-6
    2018, 38(9):  1268-1273. 
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    Objective To investigate effects of over-expression/knockdown SFRP5 on glucose metabolism in hepa1-6 hepatocarcinoma cells of mice. Methods Hepa1-6 hepatocarcinoma cell lines, established using adenovinus infection tool, are divided into three groups: control group(Ad-GFP), over-expression SFRP5 group(Ad-SFRP5), and knockdown SFRP5 group(Ad-shSFRP5). Glucose uptake rate was detected by glucose oxidase method(GOD). Gene expressions at mRNA and protein levels were determined by qRT-PCR and Western blotting. Results Compared with control group, over-expression SFRP5 increased glucose uptake rate, decresed PEPCK (P<0.05) and G6Pase expression (P<0.01)and increased insulin-stimulated InsR (P<0.01), AKT (P<0.05) phosphorylation in hepa1-6 cells. Knockdown SFFRP5 group showed an opposite result. Conclusions Over-expression SFRP5 could improve glucose metabolism through decreasing hepatic gluconeogenesis and enhancing insulin signaling pathway.
    Homocysteine thiolactone- endoplasmic reticulum stress pathway promotes HUVECs adhesion
    2018, 38(9):  1274-1279. 
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    Objective Investigates the potentials mechanisms that HTL promotes human umbilical vein endothelial cells (HUVECs) via endoplasmic reticulum stress pathway. Methods Detect the expression of NF-κB p65 in the rat thoracic aortic dissection tissue treated by HTL. Culture HUVECs, dealing with HTL on time dependent and does dependent. We detect the expression of endoplasmic reticulum stress protein Bip and Chop. Meanwhile we detect the expression of adhesive protein VCAM-1 and ICAM-1. Use the endoplasmic reticulum stress agonist and inhibitor deal with HUVEC, respectively. Then detect the affection of endoplasmic reticulum stress agonist and inhibitor on the expression of the adhesive protein in HUVECs induced by HTL, respectively. Use the protein interaction prediction tool STRING predicts the interaction between endoplasmic reticulum stress protein and adhesive protein. Results HTL induce the endothelial injury in isolated vessels; HTL increase the expressions of endoplasmic reticulum stress protein Bip and Chop in HUVECs (n=3,P<0.05); HTL upregulates the expressions of adhesive protein VCAM-1 and ICAM-1 in HUVECs (n=3,P<0.05); Endoplasmic reticulum stress agonist promotes the expression of adhesive protein VCAM-1 and ICAM-1 in HUVECs (n=3,P<0.05); Endoplasmic reticulum stress inhibitor dowmregulates the expression of adhesive protein VCAM-1 and ICAM-1 in HUVECs (n=3,P<0.05);The protein interaction prediction tool STRING predicts the endoplasmic reticulum stress protein and adhesive protein have interactions. Conclusion: HTL might promote endothelial cell adhesion via endoplasmic reticulum stress pathway.
    Role and molecular mechanism of miR-185 in aberrant methylation of T cells in pregnancy patients with systemic lupus erythematosus
    2018, 38(9):  1280-1285. 
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    Objective To investigate whethermiR-185 plays a role in the pregnancy associated with SLE. Methods Real time PCR and Western blot analysis were used to investigate the role of miR-185 in aberrant methylation of T cells in SLE patients and analyze its molecular mechanism by comparing with healthy populations. Results The results revealed that miR-185 was significantly upregulated in CD4+ T cells from patients with pregnancy complicated with SLE and its degree of over-expression was inversely correlated with DNA methyltransferase 1 (DNMT1) mRNA levels. Target gene of miR-185 prediction analysis and dualluciferase reporter assays confirmed that DNMT1 was a direct target of miR-185. Furthermore, over-expression of miR-185 in CD4+ T cells from healthy donors led to the DNA hypo-methylation and up-regulation of genes encodingCD11a and CD70. Inhibition of miR-185 expression in CD4+ T cells from patients with SLE caused revers effects. Conclusions This study indicated that miR-185 contributes to DNA hypo-methylation of CD4+ T cells in pregnancy patients with systemic lupus erythematosus by targeting DNA methyltransferase 1. Thus, miR-185 may represent apotential therapeutic target for SLE intervention.
    Parthenolide alleviates oxygen-glucose deprivation/reperfusion-induced ischemic injury in PC12 cells
    2018, 38(9):  1286-1291. 
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    Objective To explore the neuroprotective effects of PN against ischemia/reperfusion (I/R) induced injuries and the underlying mechanisms. Methods PC12 cells were cultured in vitro, and divided into culture group, the oxygen-glucose deprivation and reperfusion (OGD/R) group, and PN group (1, 5, 10 and 20 μmol/L, n=3 in each group). CCK-8 assay was used to detect the cell viability. Using the kits, the activities of caspase-3, catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx), and the levels of lactic dehydrogenase (LDH) and reactive oxygen spices (ROS) were determined. The protein expression of Bcl-2, Bax, p-Akt/Akt and p-GSK-3β/GSK-3β were detected using western blot. Results Compared with control group, the PC12 cells viability , the activities of catalase, SOD and GPx, and the levels of LDH, ROS, Bcl-2, and phosphorylation of Akt and GSK-3β were significantly decreased in the OGD/R group (P<0.05), with increased level of ROS, Bax-1 expression and caspase-3 activity (P<0.05). But PN treatment could significantly alleviate these changes in PC12 cells, compared with OGD/R group (P<0.05). Conclusions PN is a potential therapy for the cerebral I/R injury.
    Sesquiterpene lactones alleviate insulin resistance and early renal injury in diabetic mice
    2018, 38(9):  1292-1297. 
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    Objective To observe the state of insulin resistance and chronic inflammatory in C57BKS db/db mice, and to investigate the role of sesquiterpene lactones (pathenolide, PTN). Methods The db/m mice were injected with normal saline (db/m+NS) as control group, db/db mice with normal saline (db/db+NS) as experimental group and db/db mice with intraperitoneal injection of PTN(1.0 mg/kg qod)as intervention group (db/db+PTN). In 8, 12 and 16 weeks the blood, urine sample, kidney and liver were taken from the mice. Tests had been made on albumin, creatinine, glucose, lipids, insulin (radioimmunoassay), MCP-1, IL-6 (ELISA) in serum and albumin, creatinine in urine. And the semi-quantitive analysis of tissue MCP-1 and NF-кB levels were also done through immunohistochemistry method. Results 1) db/db mice had elevated blood lipids, fatty liver and other metabolic abnormalities such as hyperglycemia, hyperinsulinemia and insulin resistance. The level of urinary albumin was increased and pathology showed enlargement of glomerulus and matrix. And inflammation factor increased significantly both in serum and kidney. 2) After the therapy of PTN, both the serum MCP-1, IL-6, NF-kB and the NF-кB, MCP-1 expression in the kidney in 12 weeks old db/db mice were significantly lower than the db/db group. The level of HOMA-IR in db/db+PTN group in 12 weeks old was significantly lower than the db/db group, and the degree of fatty liver was significantly relieved. Conclusions PTN can reduce the inflammatory reaction, alleviate insulin resistance, and improve fat liver and prognosis of early diabetic nephropathy.
    Immunomodulation of emodin and its effect on the expression of TNF-α and IL-10 in splenocytes from mice
    2018, 38(9):  1298-1302. 
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    Objective To investigate the immunomodulatory effects of emodin and its effect on the expression of TNF-α and IL-10 in peripheral blood and splenocytes in mice. Methods ICR mice were randomly divided into control group, cyclophosphamide group, emodin high and low dose (10 and 5 mg / kg) group. After 7 days, the thymus and spleen index, the content of serum hemolysin and peripheral blood lymphocyte transformation rate were analyzed. The expression of TNF-α and IL-10 in peripheral blood was detected by ELISA. RT- PCR was used to detect the changes of TNF-α and IL-10 mRNA expression in mouse spleen cells. Results The application of emodin reduced the thoracic spleen index and peripheral lymphocyte transformation rate, but increased the serum hemolysin level in mice. The level of TNF-α in emodin group was decreased and the level of IL-10 was increased. The mRNA expression of IL-10 in spleen cells of emodin group was increased and the expression of TNF-α mRNA was decreased. Conclusions Emodin can improve the humoral immune function of mice and exhibit good anti-inflammatory activity, but it has certain inhibitory effect on immune organs and cell immune function.
    Silencing of FSTL1 silence reduces tunicamycin-induced endoplasmic reticulum stress and apoptosis in chondrocytes
    2018, 38(9):  1309-1314. 
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    Objective To investigate the effects of specific silencing of follistatin-like protein 1 (FSTL1) on tunicamycin-induced endoplasmic reticulum stress and apoptosis in chondrocytes. Methods Rabbit knee articular cartilage was obtained. Chondrocytes were harvested and cultured. The cells were divided into control group, tunicamycin group, tunicamycin+siRNA-FSTL1 group and tunicamycin+siRNA-NC group. The cell proliferation was detected by MTT assay. Cell apoptosis was detected by flow cytometry. The expressions of FSTL1, Bcl-2 and Bax genes were detected by real-time fluorescence quantitative polymerase chain reaction. The expressions of PERK, p-PERK, GRP78, ATF4, CHOP, Cal, eIF2α and p-eIF2α proteins were detected by Western blot. Results Compared with the tunicamycin group and tunicamycin+siRNA-NC group, the cell proliferation abilities in tunicamycin+siRNA-FSTL1 group were significantly increased (P<0.05), the apoptotic rate was decreased (P<0.05), the relative expression levels of FSTL1 and Bax mRNA were decreased, while the relative expression level of Bcl-2 mRNA was increased (P<0.05), the relative expression levels of PERK and eIF2α proteins were increased, while the relative expression levels of p-PERK, GRP78, ATF4, CHOP, Cal and p-eIF2α proteins were decreased (P<0.05). Conclusions Specific silencing of FSTL1 gene expression in chondrocytes could effectively reduce ERS and apoptosis. The mechanism might be related to inhibition of PERK signal pathway.
    Application of subcutaneous infusion unremittingly of insulin in glucose management of patients underwent total pancreatectomy
    2018, 38(9):  1315-1318. 
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    Objective To investigate the effectiveness and safety of subcutaneous infusion unremittingly of insulin in the glucose management of patients underwent total pancreatectomy and sum up the basal rate setting range. Methods We enrolled in 4 patients underwent total pancreatectomy (1 male, 3 females), 48-74 years old, treated with subcutaneous infusion unremittingly of insulin and set basal rate in accordance with six paragraph method after total pancreatectomy in Peking Union Medical College Hospital from January 2012 to January 2017, and summarized the average of the whole day glucose, the coefficient of variation of the whole day glucose and the daily dose of insulin. Results The median of average of the whole day glucose of patients was 8.70 mmol/L. The median of coefficient of variation of the whole day glucose of patients was 0.21. Patient 1 and Patient 4 had hypoglycemia at night or fasting during the use of artificial pancreas, no severe hypoglycemia was observed. The median of daily dose of insulin of patients was 0.27 IU/kg. The basal rate setting range was 0~4: 0~0.9X,4~9: 0~1.0X,9~12: 1.2~1.8X,12~17: 1.2~1.8X,17~21: 0.8~2.2X,21~24: 0~0.8X (X was average basal rate). The median of average based dosage during the day and the night was 0.48 IU/h and 0.21 IU/h, respectively. Conclusions Application of subcutaneous infusion unremittingly of insulin can significantly reduce glucose fluctuations and the amount of insulin throughout the day, the based dosage during the night should be set far less than the based dosage of full day in patients underwent total pancreatectomy.
    Clinical analysis of 37 cases of pulmonary large-cell neuroendocrine carcinomas(LCNECs)
    2018, 38(9):  1319-1322. 
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    Objectives To investigate the clinical character of the large-cell neuroendocrine carcinomas(LCNECs), and analyze the clinical factors or treatment methods related to prognosis. Methods Collect the 37 patients data from 1994.4.30 to 2014.4.30 in our hospital(PUMCH), and analyzed retrospectively. Results LCNEC occurs in older men with heavy smoking history, clinical manifestations, imaging and laboratory examination lack of specificity. Immunohistochemically neuroendocrine specific markers Syn, CgA and CD56 positive expression rates were: 75.7%、59.5% and 67.6%, respectively. 27 patients receive surgical treatment, 10 patients received adjuvant chemotherapy, 8 underwent palliative radiotherapy. Univariate analysis indicated that tumor-node-metastasis (TNM) stage(P<0.01) is prognostic factor. Surgery is a prognostic factor for patients with limited term(p<0.05). for patients with stage III radiotherapy is a prognostic factor(p<0.05). Conclusion LCNEC lack specific clinical symptoms, diagnosis depends on pathology, the treatment effect is poor. TNM stage is an important prognostic factor. Surgery for the patients with limited stage affect the prognosis, radiotherapy for patients with stage III may improve the survival rate.
    FGF21 inhibits omentin expression in adipocytes
    2018, 38(9):  1325-1326. 
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    ResolvinD1 improves insulin resistance in type 2 diabetic mice
    2018, 38(9):  1327-1328. 
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    Research progress in key cells and molecules in pathogenesis of pulmonary fibrosis
    2018, 38(9):  1329-1332. 
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    Pulmonary fibrosis (PF) is a chronic disorder of the interstitial parenchyma that results in the disruption of lung architecture and is seriously harmful to human health. Various cells and molecules were found to participate in the complex process of PF formation, and identified as key factors to induce the incidence of PF. These cells and molecules may be important targets for anti-PF drugs. This article reviews the current research progress in roles of key cells and molecules in pathogenesis of PF, so as to provide a reference for the further research and development of anti-PF drugs.
    Role of extracellular vesicles derived from apoptotic tumor cells in cancer
    2018, 38(9):  1333-1336. 
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    Extracellular vesicles (EVs) are spherical membranous vesicles surrounded by lipid bilayers. Apoptotic tumor cells-derived EVs (Apo-EVs), also named apoptosis body, were produced by apoptotic tumor cells. Functionally these Apo-EVs contained many active molecules and subcellular organelles, thus mediated signaling transduction among tumor cells and play an essential role in tumorigenesis. We summarized the role of Apo-EVs in cancer development and metastasis, also introduce its application in clinic setting such as the biomarker of diagnosis and prognostic as well as delivery carrier of therapeutic drug.
    Mechanism of ferroptosis and its significance in the related diseases
    2018, 38(9):  1337-1341. 
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    It is found in recent years that ferroptosis is a kind of regulatory cell death induced by iron dependent lipid peroxidation and reactive oxygen species (ROS) in recent years.There are significant differences in cell apoptosis, autophagy, and programmed bad death in cell morphology and biochemical indexes. It is involved in many clinical diseases such as tumor, nervous system and ischemia-reperfusion injury. Understanding ferroptosis in depth can provide new ideas for prevention and treatment of related diseases.
    Mechanism and clinical effect of proprotein convertase subtilisin/kexin type 9 inhibitors to reduce serum LDL-C
    2018, 38(9):  1342-1347. 
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    Low density lipoprotein cholesterol (LDL-C) has been demonstrated to be closely involved with Atherosclerotic cardiovascular disease (ASCVD). Clinical guidelines indicate that Statins serve as the first choice to lower LDL-C, there remains some patients can not be tolerable to statins, or even large doses of statins fail to achieve the optimal level of LDL-C. PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors can significantly reduce serum LDL-C level with good tolerance and safety. Recently, PCSK9 inhibitors have been approved to be used clinically by FDA.
    Research progress on infection and inflammatory response in preterm birth
    2018, 38(9):  1348-1351. 
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    Preterm birth refers to delivery before 37 weeks of gestation, which can cause neonatal morbidity and death. Although there are many potential causes of pregnancy related complications, infection and inflammation have been identified as an important risk factor for preterm birth. Preterm birth is a global public health problem, but the role of infection factors and immune pathways in the pathogenesis of preterm birth is still not clear.
    Research progress on the innate immune in Brucella infection
    2018, 38(9):  1352-1355. 
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    Brucella is an intracellular bacterium responsible for brucellosis, a worldwide zoonosis. It acts as a stealthy pathogen and modulates host immune responses. Brucella has developed well organized strategies that allow it to evolve and interfere with innate immune recognition , Understanding the innate immune responses triggered by Brucella is critical for the development of new vaccines, and prevention and control of brucellosis.
    Research advance of GATA3 in lymphoid malignancy
    2018, 38(9):  1356-1360. 
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    GATA-binding protein 3 (GATA3) plays an important role in regulating lymphocyte differenciation, promoting naive T cells to differeciate towards TH2 direction and supressing the differentiation of B lymphocyte or myeloid cells. Mutation or abnormal expression of GATA3 drices the development and progression of lyphoid malignancies through affecting tumor microenvironment and transmitting false effects frm other signal pathways. GATA3 expression is a prognostic marker in peripheral T-cell lymphoma. The research on medication targetting GATA3 has shown a great future.
    Research progress on microRNA in cancer and cancer stem cells
    Xiao-Tao XU
    2018, 38(9):  1361-1365. 
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    Application and evaluation of LPR teaching mode in military medical university
    2018, 38(9):  1366-1369. 
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    Objective LPR teaching mode is a kind of composite teaching mode covering lecture-based learning (LBL), problem-based learning (PBL) and research-based learning (RBL). LPR teaching mode was applied in military medical university and the effect of LPR was evaluated. Methods Eighty undergraduate students of grade 2012 and 2013 were randomly selected from a military medical university. Constructing evaluation scale which was used to evaluate the teaching effect of LPR teaching mode. We received 67 valid questionnaires. The 67 undergraduate students all experienced lecture-based learning and problem-based learning teaching mode (LBL+PBL), namely the LP teaching mode. Among them, only part of the undergraduate students participated in the extracurricular scientific research, namely the LPR teaching mode. Results The undergraduate students who have experienced the LPR teaching mode generally think of themselves making great progress in master and use of knowledge, cognitive competence, comprehensive quality and innovation ability. The environment of extracurricular scientific research in military medical university was favorable and continue to improve. Conclusions In a word, LPR teaching mode is beneficial for undergraduate students. However, the further advance of LPR teaching mode puts forward higher requirements for teachers and school administrators.
    Practice in English teaching of forensic medicine for the international students in Zhejiang University
    2018, 38(9):  1370-1372. 
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    There is rich resource of forensic medicine in Zhejiang University School of Medicine. It is necessary to teach forensic medicine in English for the national medical students. There are three points of ten years practice in English teaching of forensic medicine in Zhejiang University: 1. Training of the local team of core forensic medicine teachers; 2. Integration of judicial expertise into the combined theory and experiment teaching in forensic medicine. 3. Teaching reform with the help of “internal”and informatization plats. Hope to provide the references for the English teaching of forensic medicine for the national medical students and improve the quantity of national medical education.