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, Volume 50 Issue 5 Previous Issue   
Global burden of periodontal disease and its relation with socioeconomic development during 1990—2019
WEI Yingming,WANG Zhongxiu,LEI Lihong,CHEN Lili
J Zhejiang Univ (Med Sci), 2021, 50(5): 545-552.   https://doi.org/10.3724/zdxbyxb-2021-0321
Abstract( 207 )   HTML( 25 )     PDF(2719KB)( 112 )

Objective: To analyze the global burden of periodontal disease and its relation with socioeconomic development. Methods: Data of global disability-adjusted life year (DALY) due to periodontal disease and human development index (HDI) from 1990 to 2019 were obtained from Global Health Data Exchange (GHDx) and human development reports. The trend of the global burden of periodontal disease from 1990 to 2019 was described. The correlation between age-standardized DALY rates and HDI were examined in 2019, and between-country periodontal disease burden inequality from 1990 to 2019 was measured using health-related Gini coefficients and concentration indexes. Results: From 1990 to 2019, the global DALY rate due to periodontal disease increased from 78.63 to 85.48, and the epidemiological burden did not increase significantly. Statistical differences were found across different HDI categories for age-standardized DALY rates of periodontal disease (χ2 =44.315, P<0.01) in 2019. Linear regression analysis also revealed a negative correlation between age-standardized DALY rate of periodontal disease and HDI (β = -0.417, P<0.01) . Gini coefficients decreased from 0.361 to 0.281 and concentration indexes fell from 0.0339 to -0.0538 between 1990 and 2019.Conclusions: The global burden of periodontal disease did not increase between 1990 and 2019, though the socioeconomic-associated inequality still existed. The burden of periodontal disease was more concentrated in less developed countries, and the socioeconomic-associated inequality has increased since 2000.

Effects of Radix Rehmanniae on behavior and blood-brain barrier in Alzheimer’s disease mice
ZHAO Dapeng,LU Yunwei,YU Guran
J Zhejiang Univ (Med Sci), 2021, 50(5): 553-560.   https://doi.org/10.3724/zdxbyxb-2021-0056
Abstract( 216 )   HTML( 29 )     PDF(6862KB)( 69 )

Objective: To investigate the effects of Radix Rehmanniae on behavior and blood brain barrier (BBB) in Alzheimer’s disease mice. Methods: Thirty-eight 4-month-old APP/PS1 double transgenic mice were randomly divided into three groups: model group, Radix Rehmanniae low-dose group and Radix Rehmanniae high-dose group. Saline,Radix Rehmanniae 5?g·kg–1·d–1 andRadix Rehmanniae 12 g·kg–1·d–1 were given to each group by continuous gavage once a day for three months, respectively. The changes in activities of daily live and fear conditioning memory behavior of mice were examined by nesting behavior test and fear conditioning test, respectively. The β-amyloid protein (Aβ) depositions in cortex and hippocampal CA1 area of mice were detected by thioflavin T staining. The CD34 and activities fibrinogen (Fib) immunofluorescence double staining were used to determine the vascular endothelial integrity and BBB exudation. Results: Compared with model mice, activities of daily live were significantly improved in Radix Rehmanniae low-dose and high-dose groups (both P<0.01), the fear memory ability was significantly increased inRadix Rehmanniae high-dose group (P<0.01). The amount of Aβ deposition in cortex and hippocampal CA1 decreased significantly inRadix Rehmanniae high-dose group, the area ratio decreased significantly; the area ratio of Aβ deposition in hippocampal CA1 region inRadix Rehmanniae low-dose group also decreased (all P<0.05). The proportions of CD34 positive area of cortex in low and high doseRadix Rehmanniae groups increased, the percentage of fibrinogen positive area decreased (all P<0.05). The proportion of CD34 positive area in hippocampal CA1 region inRadix Rehmanniae high-dose group was significantly increased, the percentage of fibrinogen positive area decreased significantly (both P<0.05).Conclusions: Radix Rehmanniae, especially high-dose can improve the activities of daily live and fear conditioning memory function of APP/PS1 mice, reduce the deposition of Aβ in brain. The mechanism may be related to the reduction of BBB permeability and the protection of the integrity of BBB.

Protective effect of Fallopia denticuta against ethanol-induced gastric ulcer and its mechanism
ZOU Yulin,CUI Xiuming,XIANG Qiao,GUO Min,LIANG Yingzhong,QU Yuan,YANG Xiaoyan
J Zhejiang Univ (Med Sci), 2021, 50(5): 561-567.   https://doi.org/10.3724/zdxbyxb-2021-0055
Abstract( 171 )   HTML( 15 )     PDF(8779KB)( 54 )

Objective: To investigate the protective effect of Fallopia denticuta(FD) against ethanol-induced gastric ulcer and its mechanism. Methods: Human gastric epithelial GES-1 cells were divided into normal control group, model control group, FD 95% alcohol extract group, FD 50% alcohol extract group and FD decoction extract group. Gastric ulcer was induced by treatment with 1% ethanol in GES-1 cells. The cell proliferation was detected with MTT method in each group. Sixty SD rats were randomly divided into normal control group, model control group, ranitidine group and low-dose, medium-dose, high-dose FD 95% alcohol extract groups (150, 300, 600?mg/kg). The corresponding drugs were administrated by gavage for 14?d. The gastric ulcer model was induced by intragastric administration of anhydrous ethanol. The gastric ulcer area and ulcer inhibition rate of rats were measured in each group; the degree of gastricmucosal damage was observed by scanning electron microscopy; the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β in serum and the content of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), catalase (CAT) in gastric tissues were detected by ELISA method. Results: 95% alcohol extract of FD had the strongest protective effect on proliferation of GES-1 cells. In animal experiments, compared with the normal control group, a large area of ulcers appeared on the gastric mucosa in the model control group, while the ulcer areas of the FD groups and ranitidine group were significantly smaller than that of the model control group (all P<0.05). Compared with the model control group, FD groups and ranitidine group significantly reduced the levels of TNF-α, IL-1β, IL-6 in serum and the MDA content in the gastric tissues, and increased the activity of SOD, CAT and GSH in gastric tissues (allP<0.05).Conclusion: The 95% alcohol extract of FD can reduce the levels of TNF-α, IL-1β and IL-6 in serum and the content of MDA in gastric tissues, and increase the activity of SOD, CAT and GSH in gastric tissues to achieve the protective effect against gastric ulcer.

Protective effects of active compounds from Saussurea invo-lucrata on heart and brain of mice at simulated high altitude
ZOU Beilei,TIAN Yiting,SHI Zhiqun,ZHANG Ruxue,MA Huiping
J Zhejiang Univ (Med Sci), 2021, 50(5): 568-574.   https://doi.org/10.3724/zdxbyxb-2021-0344
Abstract( 152 )   HTML( 8 )     PDF(5877KB)( 29 )

Objective:To investigate the active compounds from Saussurea involucrata on the heart and brain of mice at simulated high altitude.Methods:Fifty healthy male adult BALB/c mice were randomly divided into normal control group, hypoxic model group, acetazolamide group, petroleum ether extract of Saussurea involucrata (PESI) group and octacosan group with 10 mice in each group. Acetazolamide group, PESI group and octacosan group were treated with acetazolamide (200?mg/kg), PESI (200?mg/kg) or octacosan (100?mg/kg) by single tail vein injection, respectively. Except normal control group, the mice were exposed to a simulated high altitude of 6000?m for 8?h in an animal decompression chamber. After the mice were sacrificed by cervical dislocation, the heart and brain were histologically observed by HE staining; superoxide dismutase (SOD) activity, total anti-oxidant capacity (T-AOC) and the content of malondialdehyde (MDA) in plasma, heart and brain tissues were detected by WST-1 method, ABTS method and TBA method, respectively; lactic acid and lactate dehydrogenase (LDH) activity in plasma, heart and brain tissues were detected by colorimetric method and microwell plate method, respectively; ATP content and ATPase activity in heart and brain tissues were detected by colorimetric method. Results: PESI and octacosane significantly attenuated the pathological damages of heart and brain tissue at simulated high altitude; increased SOD activity, T-AOC and LDH activity, and decreased the contents of MDA and lactic acid in plasma, heart and brain tissues; increased the content of ATP in heart and brain tissues; increased the activities of Na+-K+ ATPase, Mg2+ ATPase, Ca2+ ATPase and Ca2+-Mg2+ ATPase in myocardial tissue; and increased the activities of Mg2+ ATPase, Ca2+-Mg2+ ATPase in brain tissue. Conclusion: PESI and octacosan exert anti-hypoxic activity by improving the antioxidant capacity, reducing the free radical levels, promoting the anaerobic fermentation, and alleviating the energy deficiency and metabolic disorders caused by hypoxia in mice.

Protective effects of 7-hydroxyethyl chrysin on rats with exercise-induced fatigue in hypobaric hypoxia environment
MIAO Luwei,ZHAO Tong,GAO Yingchun,JING Linlin,HUANG Qiong,MA Huiping
J Zhejiang Univ (Med Sci), 2021, 50(5): 575-581.   https://doi.org/10.3724/zdxbyxb-2021-0319
Abstract( 121 )   HTML( 3 )     PDF(6342KB)( 42 )

Objective: To investigate the protective effect of 7-hydroxyethyl chrysin (7-HEC) on rats with exercise-induced fatigue in hypobaric hypoxic condition.Methods:Forty healthy male Wistar rats were randomly divided into four groups with 10 rats in each group: control group, model group, chrysin group and 7-HEC group. The rats in control group were raised at local altitude but other three groups were raised in a simulating altitude of 7000?m for hypobaric hypoxia treatment. The chrysin group and 7-HEC group were given 350?mg/kg chrysin or 7-HEC by gavage for 3?d, respectively; while the control group and model group were given the same amount of sterilized water. The weight-bearing swimming tests were performed 3?d later, and the weight-bearing swimming time was documented. After rats were sacrificed, the liver and skeletal muscle tissue samples were taken for pathological examination and determination of lactate, malondialdehyde (MDA), total superoxide dismutase (T-SOD) and glycogen levels. Blood urea nitrogen was also determined. Results:Compared with the model group, weight-bearing swimming times were significantly prolonged in 7-HEC group [(2.58±0.77) vs. (4.04±1.30)?min, P<0.01]; pathological changes in liver and skeletal muscle tissue were attenuated; generation rate of blood urea nitrogen [(3.24±0.93) vs. (2.22±0.60) mmol·L–1·min–1, P<0.05], lactate [liver: (0.14±0.05) vs. (0.10±0.03)?mg·g–1·min–1, skeletal muscle: (0.26±0.06) vs. (0.18±0.07) mg·g–1·min–1] and MDA [liver: (1.37±0.48) vs. (0.78±0.28)?nmol·mg–1·min–1, skeletal muscle: (0.87±0.19) vs. (0.63±0.11)?nmol·mg–1·min–1] were significantly reduced (all P< 0.05); glycogen content [liver: (15.16±2.69) vs. (18.89±2.88)?mg/g, skeletal muscle: (1.46±0.49) vs.(1.78±0.48)?mg/g] and T-SOD [liver: (1.87±0.01) vs. (2.68±0.12) U/mL, skeletal muscle: (5.46±0.42) vs. (6.52±0.96) U/mL] were significantly improved (allP<0.05).Conclusion:7-HEC has significant protective effect on the rats with exercise-induced fatigue in hypobaric hypoxia condition.

Resveratrol inhibits the migration, invasion and epithelial-mesenchymal transition in liver cancer cells through up-regulating miR-186-5p expression in vitro
SONG Feifeng,ZHANG Yiwen,PAN Zongfu,ZHANG Qi,LU Xixuan,HUANG Ping
J Zhejiang Univ (Med Sci), 2021, 50(5): 582-590.   https://doi.org/10.3724/zdxbyxb-2021-0197
Abstract( 146 )   HTML( 5 )     PDF(11736KB)( 55 )

Objective: To investigate the molecular mechanism of resveratrol inhibiting the metastasis of liver cancer in vitro. Methods:HepG2 and Huh7 cells were treated with different concentrations of resveratrol, and the cell viability was determined by CCK-8 assay to determine the optimal concentration of resveratrol for subsequent experiments. The expressions of miR-186-5p in liver cancer tissues and liver cancer cells were determined by quantitative real-time RT-PCR. The migration and invasion of HepG2 and Huh7 cells were detected by wound healing assay and Transwell assay, and the expression levels of epithelial-mesenchymal transition (EMT) related proteins were determined by Western blotting. Results:Resveratrol with concentration of 6.25?μmol/L had no effect on the viability of HepG2 and Huh7 cells, so the concentration of resveratrol in subsequent experiments was 6.25?μmol/L. Resveratrol inhibited the wound healing and invasion of liver cancer cells; increased the expression of E-cadherin, and decreased the expression of vimentin and Twist1. The expression of miR-186-5p was significantly down-regulated in liver cancer tissues and cells compared with the adjacent tissues and normal liver cells (both P<0.05). Furthermore, resveratrol induced the expression of miR-186-5p in liver cancer cells (bothP<0.01). Overexpression of miR-186-5p suppressed the migration, invasion and EMT of liver cancer cells. Knockdown of miR-186-5p blocked the inhibition effects of resveratrol on the migration, invasion and EMT of liver cancer cells.Conclusion: Resveratrol could inhibit the metastasis of liver cancer in vitro, which might be associated with up-regulating miR-186-5p.

Protective effect of α-asarone and β-asarone on Aβ 25-35-induced inflammatory response in PC12 cells and its mechanism
SHI Jianhong,LI Ruizhi,YANG Yuanxiao,JI Liting,LI Changyu
J Zhejiang Univ (Med Sci), 2021, 50(5): 591-600.   https://doi.org/10.3724/zdxbyxb-2021-0162
Abstract( 138 )   HTML( 2 )     PDF(6314KB)( 29 )

Objective: To investigate effects of α-asarone and β-asarone on Aβ25-35-induced PC12 cell injury and related mechanisms. Methods:Aβ toxic injury cell model was induced by Aβ25-35 in PC12 cells. PC12 cells were divided into blank control group, model control group, α-asarone group (0.5, 1.0, 1.5?μg/mL), β-asarone group (6.3, 12.5, 25.0?μg/mL), vasoactive intestinal peptide (VIP) group, and VIP antagonist control group. Cell survival rate was detected by CCK-8 kit; cell apoptosis rate was detected by flow cytometry. The levels of inflammatory cytokines interleukin (IL)-1, IL-10, tumor necrosis factor (TNF)-α, oxidation-related inducible nitric oxide synthase (iNOS), nitric oxide (NO), apoptosis factors caspase-3 and p53 were detected by ELISA method. The expressions of C-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK) were detected by Western blotting. Results:Compared with model control group, cell survival rates of α-asarone group, β-asarone group and VIP group increased; the cell apoptosis rate decreased; levels of apoptosis-related factors caspase-3, p53, inflammatory factors IL-1, TNF-α decreased; IL-10 level increased; levels of oxidization-related factors iNOS and NO decreased; the expression of JNK and p38MAPK protein decreased (all P<0.05). After VIP antagonist intervention, the survival rate of β-asarone group decreased; apoptosis rate increased; apoptosis related factors caspase-3, p53, inflammatory factors IL-1, TNF-α increased; IL-10 decreased; oxidation related factors iNOS and NO increased; the expression of JNK and p38MAPK protein increased (allP<0.05); while there were no significant changes in these indicators of α-asarone group (allP>0.05).Conclusion: α-asarone and β-asarone have protective effects on PC12 cell injury induced by Aβ25-35. β-asarone may inhibit inflammatory factors and oxidation-related factors through promoting VIP secretion, regulating JNK/MAPK pathway, and reducing PC12 cell apoptosis; however, the effect of α-asarone may be not related to VIP secretion.

Natural medicinal ingredients induce tumor ferroptosis and related mechanisms
XUAN Zixue,ZHANG Yiwen,PAN Zongfu,ZHENG Xiaowei,HUANG Ping
J Zhejiang Univ (Med Sci), 2021, 50(5): 601-606.   https://doi.org/10.3724/zdxbyxb-2021-0198
Abstract( 189 )   HTML( 9 )     PDF(2448KB)( 46 )

Ferroptosis is an iron-dependent programmed cell death characterized by reactive oxygen species-induced lipid peroxide accumulation, which is different from cell apoptosis, pyroptosis, necrosis or autophagy. Ferroptosis plays an important role in the regulation of tumorigenesis and tumor development. Recent studies have shown that natural medicinal ingredients can induce ferroptosis in tumor cells through glutathione (GSH)/glutathione peroxidase 4 (GPx4) pathway, iron metabolism, lipid metabolism or other mechanisms. It has been reported that more than 30 natural medicinal ingredients can induce ferroptosis in tumor cells with multiple pathways and multiple targets. This article reviews the current research progress on the antitumor effects of natural medicinal ingredients through inducing cell ferroptosis.

Relationship between salt-inducible kinase 2 (SIK2) and lymph node metastasis in colorectal cancer patients complicated with chronic schistosomiasis
WU Chao,WANG Yu,GAO Hongliang,ZHANG Yi,DAI Min,LI Shu
J Zhejiang Univ (Med Sci), 2021, 50(5): 607-613.   https://doi.org/10.3724/zdxbyxb-2021-0157
Abstract( 124 )   HTML( 12 )     PDF(17121KB)( 46 )

Objective:To investigate the relationship between salt-inducible kinase 2 (SIK2) and lymph node metastasis in colorectal cancer patients complicated with chronic schistosomiasis. Methods:Tissue specimens were collected from 363 patients who were diagnosed as colorectal cancer by clinical and pathological examination in Wuhu Second People’s Hospital from June 2015 to June 2020. Fifty-six patients were colorectal cancer complicated with schistosomiasis (CRC-S) and 307 patients were colorectal cancer not complicated with schistosomiasis (CRC-NS). The clinical and pathological data of the patients were analyzed to explore the relationship between chronic schistosomiasis and colorectal cancer. Immunohistochemistry and Western blotting were used to detect the distribution and expression of SIK2 in colorectal cancer specimens. The relationship between SIK2 and lymph node metastasis of CRC-S was analyzed. Results:The rate of lymph node metastasis in CRC-S group was significantly higher than that in CRC-NS group (62.5% vs. 47.2%, P<0.05). In CRC-S patients with lymph node metastasis, schistosome eggs were distributed mainly in tumor tissues (25/35, 71.4%), while in patients with CRC-S without lymph node metastasis, schistosome eggs were distributed mainly in paracancerous tissues (17/21, 81.0%) (χ2=14.243, P<0.01). The SIK2 was mainly located in cytosol, and its expression in tumor tissues was higher than that in paracancerous tissues. Compared with CRC-NS patients, the expression of SIK2 in CRC-S patients was significantly increased; the expression of SIK2 in patients with lymph node metastasis was higher than that in patients without lymph node metastasis; and the expression of SIK2 in patients with schistosome eggs in cancer tissues was higher than that in patients with schistosome eggs in paracancerous tissues (allP<0.01).Conclusions:Lymph node metastasis is more likely to be occurred in colorectal cancer patients with schistosomiasis, especially in those with schistosome eggs in tumor tissues. The expression of SIK2 may be correlated with chronic schistosomiasis, egg distribution and lymphatic metastasis.

Establishment of a hypobaric hypoxia-induced cell injury model in PC12 cells
ZHANG Dongmei,CAO Qilu,JING Linlin,ZHAO Xiuhua,MA Huiping
J Zhejiang Univ (Med Sci), 2021, 50(5): 614-620.   https://doi.org/10.3724/zdxbyxb-2021-0343
Abstract( 202 )   HTML( 9 )     PDF(4740KB)( 52 )

Objective: To construct a hypobaric hypoxia-induced cell injury model. Methods:Rat pheochromocytoma PC12 cells were randomly divided into control group, normobaric hypoxia group and hypobaric hypoxia group. The cells in control group were cultured at normal condition, while cells in other two groups were cultured in normobaric hypoxia and hypobaric hypoxia conditions, respectively. CCK-8 method was used to detect cell viability to determine the optimal modeling conditions like the oxygen concentration, atmospheric pressure and low-pressure hypoxia time. The contents of lactate dehydrogenase (LDH), superoxide dismutase (SOD) and malondialdehyde (MDA) were detected by microplate method. The apoptosis ratio and cell cycle were analyzed by flow cytometry. Results: The hypobaric hypoxia-induced cell injury model can be established by culturing for 24?h at 1% oxygen concentration and 41?kPa atmospheric pressure. Compared with the control group and normobaric hypoxia group, the activity of LDH and the content of MDA in hypobaric hypoxia group were significantly increased, the activity of SOD was decreased, the percentage of apoptosis was increased (all P<0.05), and the cell cycle was arrested in G0/G1 phase.Conclusion: A stable and reliable cell injury model induced by hypobaric hypoxia has been established with PC12 cells, which provides a suitable cell model for the in vitro experimental study on nerve injury induced by hypoxia at high altitude.

The mechanism of rapamycin in promoting asthmatic regulatory T cell differentiation and function in vitro
JIN Hualiang,ZHOU Yan,WANG Limin
J Zhejiang Univ (Med Sci), 2021, 50(5): 621-626.   https://doi.org/10.3724/zdxbyxb-2021-0173
Abstract( 147 )   HTML( 7 )     PDF(4189KB)( 30 )

Objective:To investigate the mechanism of rapamycin in promoting asthmatic regulatory T cell differentiation in vitro. Methods: Asthma model was prepared by sensitization and challenge of ovalbumin in mice. Spleen CD4+CD25 ?T cells were sorted from the asthmatic mice and normal mice by ultrahigh speed flow cytometer, and divided into three groups. Transforming growth factor-β and interleukin-2, or combined with rapamycin (final concentration of 500?nmol/L) were given in the model group or the rapamycin group. The levels of Treg cells and CD4+CD25 ?T cells were detected by flow cytometry. The phosphorylation level of downstream proteins of S6 and Akt in the mTORC1/2 signaling pathway were examined by Western blotting. Results:Compared with the model group, the differentiation level of Treg cells in the rapamycin group was significantly increased, the proliferation level of CD4+CD25 ?T cells was decreased, and the phosphorylations of the mTORC1/2 substrates, S6 protein and Akt were decreased (all P<0.05).Conclusion:Rapamycin can promote the differentiation and function of Treg cells via inhibition of the mTORC1/2 signaling pathway.

Metformin alleviates intestinal epithelial barrier damage by inhibiting endoplasmic reticulum stress-induced cell apoptosis in colitis cell model
WANG Jingang,CHEN Chunxiao,REN Yuhan,ZHOU Xinxin,YU Shan
J Zhejiang Univ (Med Sci), 2021, 50(5): 627-632.   https://doi.org/10.3724/zdxbyxb-2021-0242
Abstract( 205 )   HTML( 15 )     PDF(3644KB)( 43 )

Objective:To investigate the effect and mechanism of metformin on intestinal epithelial barrier injury in ulcerative colitis. Methods:A cell model of colitis was established by co-culture of human colon cancer cell line Caco-2 and human monocyte cell line THP-1. The colitis model cells were treated with metformin at concentration of 1?mmol/L for 24?h. Flow cytometry was used to detect Caco-2 cell apoptosis, and Western blotting was used to detect the protein expression of tight junction proteins and endoplasmic reticulum stress-related proteins. Results: After metformin treatment, the apoptosis rate of Caco-2 cells was decreased from (14.22±2.34)% to (9.88±0.61)% (t=3.119, P<0.05), and the expression levels of tight junction protein-1 and claudin-1 increased (t=5.172 and 3.546, both P<0.05). In addition, the expression levels of endoplasmic reticulum-related proteins glucose regulated protein (GRP) 78, C/EBP homologous protein (CHOP) and caspase-12, as well as the phosphorylation level of PRKR-like endoplasmic reticulum kinase (PERK) and eukaryotic translation initiation factor 2α (eIF2α) decreased (allP<0.05).Conclusion:Metformin may alleviate the intestinal epithelial barrier damage in colitis by reducing intestinal epithelial cell apoptosis and increasing the expression of tight junction proteins, which may be associated with the inhibition of endoplasmic reticulum stress-induced apoptotic pathway.

Evaluation of self-prepared absorbable hemostatic cellulose fibrils
WANG Lingshuang,TONG Jianxing,ZHAO Zhezhe,YANG Xiaochun
J Zhejiang Univ (Med Sci), 2021, 50(5): 633-641.   https://doi.org/10.3724/zdxbyxb-2021-0066
Abstract( 131 )   HTML( 4 )     PDF(13789KB)( 19 )

Objective:To evaluate the effectiveness and safety of self-prepared absorbable hemostatic fibrils.Methods:A kind of absorbable hemostatic fibrils were prepared by self-developed patent technique. The physical form and molecular structure of the fibrils and a marketed product Surgicel? were characterized by general observation and infrared spectroscopy; the carboxyl content, pH value and relative molecular mass of fibrils were determined by potentiometric titration method, pH meter and copper ethylenediamine method, respectively. The behavior of the fibrils and Surgicel? in contact with blood was observed by inverted microscope, the cytotoxicity was evaluated by agarose diffusion cell assay in vitro. The external iliac artery hemorrhage model and the back muscle infiltration model in rats were established. The hemostatic effectiveness of the fibrils was investigated by hemostasis time and blood weight, and the degradation and biosafety of fibrils were investigated by observation photography, immune organ weighing, hematology and coagulation index measuring, and histopathological examination. Results:The fibrils and Surgicel? had similar molecular structures. Compared with the raw material regenerated cellulose, the typical carboxyl stretching vibration absorption peak of –COOH appeared near 1727?cm–1 in both fibrils and Surgicel?. The carboxyl content of the two materials was about 20%, and the pH value was about 3. The relative molecular mass of the fibers after oxidation was 4466±79, which was close to that of Surgicel?(P>0.05). After contacting with blood, the volume of fibrils and Surgicel? expanded, and absorbed blood of dozens of times as their own weight. The results of agar diffusion test showed that the fibrils had no cytotoxicity. The results of animal experiments showed that the hemostasis completed within 2?min, and there was no significant difference in blood weight and speed of hemostasis between two products (both P>0.05). The fibrils could be degraded 1 week after being implanted to the bleeding sites of the muscle. There were no pathological effects on the appearance, body weight, food intake, immunological tissue thymus, spleen, lymph nodes, hematology and coagulation indexes of the rats, and no obvious abnormality found in the histopathological examination.Conclusion:The prepared absorbable hemostatic fibrils have excellent biological safety and effectiveness.

The roles of epigenetic modifications in neurodegenerative diseases
QU Wenzheng,ZHUANG Yingliang,LI Xuekun
J Zhejiang Univ (Med Sci), 2021, 50(5): 642-650.   https://doi.org/10.3724/zdxbyxb-2021-0160
Abstract( 232 )   HTML( 30 )     PDF(2956KB)( 111 )

In neuronal system, epigenetic modifications are essential for neuronal development, the fate determination of neural stem cells and neuronal function. The dysfunction of epigenetic regulation is closely related to occurrence and development of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease. Abnormally elevated DNA methylation inhibits the expression of some DNA repair-related genes and affects the progression of Huntington’s disease. In the brain of Alzheimer’s disease patients, the levels of H3K27ac and H3K9ac histone modifications increased. In addition, the alteration of RNA methylation in animal models of Alzheimer’s disease and Parkinson’s disease showed discrepancy trends. Therefore, epigenetic modifications may serve as potential therapeutic targets for neurodegenerative diseases. Here, we summarize the recent progress of the roles of epigenetic modifications in neurodegenerative diseases.

The roles of GluN3-containing N-methyl-D-aspartate receptor in central nerve system
SUN Qi,CAO Wei,LUO Jianhong
J Zhejiang Univ (Med Sci), 2021, 50(5): 651-658.   https://doi.org/10.3724/zdxbyxb-2021-0167
Abstract( 139 )   HTML( 10 )     PDF(2720KB)( 37 )

The N-methyl-D-aspartate receptor (NMDAR) in central nerve system is mostly composed of GluN1 and GluN2 subunits. The classical NMDAR has been intensively studied. However, GluN3?containing NMDAR is much less expressed and have atypical channel properties. Recently, accumulating evidences have revealed two types of GluN3?containing NMDAR: glutamate-gated GluN1/GluN2/GluN3 NMDAR and glycine-gated GluN1/GluN3 NMDAR. The former may play important roles in regulating synapse maturation and pruning non-used synapses, and its elevated expression at the adult stage may alter synaptic reorganization in some neuropsychiatric disorders. The latter is expressed in the medial habenula and involves in control of aversion. This article reviews the recent progresses on the expression, functional properties of GluN3?containing atypical NMDARs and the physiological and pathological relevance.

Research progress of phosphodiesterase inhibitors in inflammatory bowel disease treatment
SHI Jianrong,MA Wangqian,TANG Huifang
J Zhejiang Univ (Med Sci), 2021, 50(5): 659-665.   https://doi.org/10.3724/zdxbyxb-2021-0170
Abstract( 188 )   HTML( 12 )     PDF(2041KB)( 65 )

Inflammatory bowel disease is a recurrent chronic intestinal inflammatory disease with unknown etiology and no effective treatment. Phosphodiesterase (PDE) regulates a variety of physiological and pathophysiological processes by mediating the hydrolysis of intracellular second messengers cyclic adenosine monophosphate and cyclic guanosine monophosphate. In recent years, a series of researches suggest that PDE inhibitors such as several PDE4 inhibitors, PDE5 inhibitors (sildenafil, tadalafil and vardenafil), PDE3 inhibitors (cilostazol), PDE9 inhibitor (PF-04447943) and PDE3/PDE4 double inhibitor (pumafentrine) have ameliorating effect on experimental colitis in animals. In clinical trials, PDE4 inhibitor apremilast showed more therapeutic advantage than tetomilast. This article reviews the recent research progress of PDE inhibitors in treatment of inflammatory bowel disease.

Progress on the application of positron emission tomography imaging of cannabinoid type 1 receptor in neuropsychiatric diseases
MA Lijuan,WU Shuang,ZHANG Kai,TIAN Mei,ZHANG Hong
J Zhejiang Univ (Med Sci), 2021, 50(5): 666-673.   https://doi.org/10.3724/zdxbyxb-2021-0063
Abstract( 238 )   HTML( 12 )     PDF(2256KB)( 52 )

Cannabinoid type 1 receptor (CB1R), as the major member of the endocannabinoid system, is among the most abundant receptors expressed in the central nervous system. CB1R is mainly located on the axon terminals of presynaptic neurons and participate in the modulation of neuronal excitability and synaptic plasticity, playing an important role in the pathogenesis of various neuropsychiatric diseases. In recent years, the consistent development of CB1R radioligands and the maturity of molecular imaging techniques, particularly positron emission tomography (PET) may help to visualize the expression and distribution of CB1R in central nervous system in vivo. At present, CB1R PET imaging can effectively evaluate the changes of CB1R levels in neuropsychiatric diseases such as Huntington’s disease and schizophrenia, and its correlation with the disease severity, therefore providing new insights for the diagnosis and treatment of neuropsychiatric diseases. This article reviews the application of CB1R PET imaging in Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, schizophrenia, post-traumatic stress disorder, cannabis use disorder and depression.

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