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    A novel antithrombotic antibody targeting the binding sites of the coagulation factor FⅨa-FⅧa complex
    Tian-yao SUN, Shi-feng JIANG, Qin XU, Jun-ling LIU, Su-ying DANG, Xue-mei FAN
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2021, 41 (9): 1133-1141.   DOI: 10.3969/j.issn.1674-8115.2021.09.001
    Abstract133)      PDF(pc) (6502KB)(383)       Save
    Objective

    ·To prepare a monoclonal antibody targeting coagulation factor Ⅸa (FⅨa), a key factor in endogenous coagulation pathways, and study its antithrombotic roles and mechanisms.

    Methods

    ·Immunization of mice, hybridoma technology, cell expression and purification were used to prepare the anti-FⅨa monoclonal antibodies of high purity. The monoclonal antibodies with high affinity for FⅨa were screened by enzyme-linked immunosorbent assay. The activated partial thromboplastin time (APTT) and prothrombin time (PT) were used to evaluate the antithrombotic effects of the monoclonal antibody. And then chromogenic substrate method was used to detect the effect of monoclonal antibody on the enzyme activity of FⅨa. The method of computer simulation of protein-protein docking was adopted to predict the possible binding sites between FⅨa and the antibody, and the binding site, was verified by competitive experiments (indirectly through the chromatic substrate method).

    Results

    ·FⅨa-4, an anti-FⅨa monoclonal antibody with high affinity, was generated. Although FⅨa-4 did not affect PT and the enzyme activity of FⅨa, it significantly prolonged APTT to 88.8 s, which was 3.5 times of the control group (25.5 s), in a concentration-gradient dependence. The protein-protein docking prediction results revealed that FⅨa-4 did not directly bind to substrate catalytic sites of FⅨa, but occupied the binding region of FⅨa and FⅧa. Competitive experiments further verified the above results. FⅨa-4 inhibited FⅩa production in a dose-dependent manner, almost completely inhibiting FⅩa production at the concentrations of 400 pmol/L, and FⅧa could correct the inhibition effect of the antibody up to nearly 50%.

    Conclusion

    ·The monoclonal antibody against FⅨa-4 is obtained. FⅨa-4 competes with FⅧa to bind FⅨa, and inhibits the conversion of FⅩ to FⅩa which is catalyzed by FⅧa-FⅨa complex; it plays an antithrombotic role mainly by inhibiting endogenous coagulation pathway.

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    Progress and controversy in comprehensive treatment of hilar cholangiocarcinoma
    Wei CHEN, Yingbin LIU
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (1): 1-8.   DOI: 10.3969/j.issn.1674-8115.2022.01.001
    Abstract76)   HTML13)    PDF(pc) (1076KB)(329)       Save

    Hilar cholangiocarcinoma is a tumor with a poor prognosis, which is difficult to diagnosis in the early stage and has caused lots of controversies in clinical treatment. At present, surgical resection provides the main possibility for cure. Precise evaluation and adequate preparation before surgery and safe, effective, standardized resection are the key methods to successful treatment. Comprehensive treatment based on chemotherapy improves the survival of patients. In the future, guided by concepts of oncology, comprehensive treatment of multiple modes, containing surgery, chemotherapy, targeted therapy, immune therapy and biological therapy, is the development trend of hilar cholangiocarcinoma treatment.

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    Expression characteristics of silent information regulator transcript 1 in intestinal tissues of neonatal necrotizing enterocolitis
    Rui CHEN, Yun ZHAO, Xiao-xia ZHAO, Dong MA, Yi-jiang HAN, Deng-ming LAI, Wei-zhong GU, Jin-fa TOU
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2021, 41 (9): 1154-1161.   DOI: 10.3969/j.issn.1674-8115.2021.09.004
    Abstract113)      PDF(pc) (4204KB)(325)       Save
    Objective

    ·To explore the expression characteristics of silent information regulator transcript 1 (SIRT1) in intestinal tissues of necrotizing enterocolitis (NEC), and preliminarily discuss the effect and possible mechanisms of SIRT1 in NEC.

    Methods

    ·From June 2018 to October 2020, 80 children with NEC who were treated by neonatal surgery in the Children's Hospital, Zhejiang University School of Medicine were divided into observation group and control group. The tissue samples of the observation group were inflammatory necrotic intestinal tubes, while those of the control group were incised intestinal tubes. The NEC children in the control group were with intestinal strictures after conservative treatment, and then were treated by surgery again. The clinical data of the two groups were collected 24 h before surgery, including procalcitonin (PCT), hypersensitive C reactive protein (hs-CRP), cytokines [interleukin-2 (IL-2), IL-4, IL-6, IL-10, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ)] in the serum, gender, gestational age and so on. The expression characteristics of SIRT1, nuclear factor-κB (NF-κB), transforming growth factor β1 (TGF-β1) and Smad3 proteins of the tissues in the two groups were detected by immunohistochemistry. IEC-6 cells of small intestinal epithelium of SD female rats were cultured in vitro. After SIRT1 expression in IEC-6 cells was inhibited by small interfering RNA (siRNA) technology, the protein expression of NF-κB was detected by Western blotting and the effects of SIRT1 on IEC-6 cells were detected by Cell Counting Kit-8 (CCK8) and Transwell migration assay.

    Results

    ·There was no significant difference in gender, gestational age, birth weight and delivery mode between the two groups. Compared with the control group, the levels of hs-CRP, PCT, IL-6 and IL-10 in the serum in the observation group increased within 24 h before surgery (all P=0.000).Compared with the margin tissues of narrow intestines in the control group, the positive expression of SIRT1 in NEC necrotic intestinal tissues in the observation group showed low expression, and the positive expression of NF-κB was overexpressed (both P=0.000). There was no significant difference in the expression of Smad3 and TGF-β1 between the two groups. The expression of SIRT1 in NEC necrotic intestinal tissue was negatively correlated with the expression of NF-κB (r=-0.592, P=0.000). After inhibiting the mRNA and protein expression of SIRT1, the relative expression of NF-κB in IEC-6 cells was increased, and the proliferation and migration ability of the cells was significantly decreased.

    Conclusion

    ·The mechanism for the SIRT1 reducing progression of NEC may be that SIRT1 can inhibit the expression of NF-κB to reduce the expression of inflammatory factors in NEC, and another possible mechanism may be that SIRT1 can protect intestinal epithelial cells by promoting cell proliferation and migration.

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    Factors related to prognosis of portoenterostomy for type Ⅲ biliary atresia
    Geng-feng JI, Zhi-bo ZHANG
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2021, 41 (9): 1142-1146.   DOI: 10.3969/j.issn.1674-8115.2021.09.002
    Abstract113)      PDF(pc) (1150KB)(321)       Save
    Objective

    ·To explore the factors related to the jaundice clearance and native liver survival after portoenterostomy (Kasai's operation) in the children with type Ⅲ biliary atresia.

    Methods

    ·The clinical data of the patients diagnosed as having type Ⅲ biliary atresia, who underwent Kasai's operation in Shengjing Hospital of China Medical University from January 2012 to January 2018, were analyzed retrospectively. According to the prognosis, the children were divided into jaundice clearance group (JC group, which was divided further into early and late JC group) and jaundice non-clearing group (JOC group), or native liver survival group and non-native liver survival group (liver transplantation/death). T/U test, χ2 test, Kaplan-Meier survival analysis, and multivariate Cox regression analysis were employed to analyze the prognostic factors.

    Results

    ·A total of 96 patients were enrolled in this study, including 48 males and 48 females. The average age of operation was (62.1±18.9) d, and the average follow-up time was (16.2±20.3) months. Direct bilirubin decreased to normal within 6 months postoperatively in 61 cases (63.5%). Compared with the JOC group, the indirect bilirubin (IBIL) level was higher and the albumin level was lower in the JC group before operation (both P<0.05). The result of Kaplan-Meier survival curve analysis showed that the native liver survival rates at 3, 6, 12 and 24 months after operation were 92.3%, 70.9%, 57.8% and 55.8%, respectively. The native liver survival rate of the JC group was higher than that of the JOC group (P=0.000). The rate was also higher in the early JC group when compared with the late JC group (P=0.001). Multivariate Cox regression analysis revealed that gender of male [P=0.049, RR=2.163 (95%CI 1.076?4.797)] and jaundice clearance [P=0.001, RR=11.488 (95%CI 2.726?48.415)] were the protective factors of 2-year native liver survival rate.

    Conclusion

    ·Preoperative IBIL and albumin levels may affect jaundice clearance in the children with type Ⅲ biliary atresia after portoenterostomy; gender of male and jaundice clearance are protective factors for 2-year native liver survival in these children.

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    Laparoscopic diagnosis and treatment of high jejunal atresia and stenosis in neonates
    Bao-hong ZHAO, Hong-xia REN, Xiao-xia WU, Yuan-yuan JIN, Wen-yue LIU, Liang ZHAO, Hui ZHANG, Xin GUO, Xue SUN
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2021, 41 (9): 1162-1168.   DOI: 10.3969/j.issn.1674-8115.2021.09.005
    Abstract91)      PDF(pc) (2950KB)(320)       Save
    Objective

    ·To investigate the effect of laparoscope on the treatment of high jejunal atresia and stenosis in neonates.

    Methods

    ·From January 2009 to December 2019, 90 neonates with high jejunal atresia and stenosis were operated on Children′s Hospital of Shanxi province. According to whether laparoscopic surgery was used or not, they were divided into laparoscopic group (n=66) and laparotomy group (n=24). In the laparoscopic group, 27 cases of type Ⅰ atresia and stenosis less than 10 cm from Treitz ligament were anastomosed under laparoscopy, and 39 cases of jejunal atresia and stenosis 10?30 cm from the Treitz ligament, underwent extraperitoneal anastomosis by expanded trocar hole with the aid of single-site laparoscope. Traditional laparotomy exploratory incision was used in the laparotomy group. The operation time, the first postoperative oral feeding time, postoperative full oral feeding time [postoperative oral feeding volume reaching 150 mL/(kg·d)], the length of hospital stay, and mortality and incidence of complications were compared between the two groups.

    Results

    ·There was no significant difference between the laparoscopic group and laparotomy group in age, gender, weight, premature infant, low birth weight, other systems malformation and pathological type. There was no significant difference in operation time between the laparoscopic group and laparotomy group [(77.0±24.0) min vs (82.0±24.0) min]. The first postoperative oral feeding time, postoperative full oral feeding time [postoperative oral feeding volume reaching 150 mL/(kg·d)], and the length of hospital stay in the laparoscopic group were shorter than those in the laparotomy group [(13.3±7.2) d, (19.1±8.1) d, (22.1±8.5) d vs (17.2±7.8) d,(23.7±10.6) d, (27.0±11.8) d, all P <0.05]. There was no significant difference between the laparoscopic group and laparotomy group in mortality (1/66 vs 2/24) and incidence of complications (7/66 vs 6/24).

    Conclusion

    ·Laparoscopic surgery is a safe and effective method in the diagnosis and treatment of neonatal high jejunal atresia/stenosis.

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    Application of modified Nutrition Risk in the Critically Ill score to critically ill elderly patients
    Xuemei LU, Lan CHEN
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (1): 16-20.   DOI: 10.3969/j.issn.1674-8115.2022.01.003
    Abstract65)   HTML8)    PDF(pc) (859KB)(293)       Save
    Objective

    ·To validate the role of the modified Nutrition Risk in the Critically Ill (mNUTRIC) score in the assessment of nutritional risk and clinical prognosis in critically ill elderly patients.

    Methods

    ·A prospective observational study was carried out. The mNUTRIC score was employed to assess the nutritional risk of elderly patients who were admitted into the intensive care unit (ICU) of Shanghai General Hospital, Shanghai Jiao Tong University between October 2020 and February 2021. Patients were divided into high nutritional risk group and low nutritional risk group based on the mNUTRIC score results. The observational end-points were transferred, discharged or death. Different nutrition risk patients' nutritional support were analyzed, including nutritional support methods, the time period before nutritional support, and energy supply conditions. The length of ICU stay, days with mechanical ventilation, and 28-day mortality of different nutrition risk patients were compared.

    Results

    ·Among critically ill elderly patients, 51.8% were at high nutritional risk. The energy compliance rate of the low nutritional risk group was 73.3%, and that of the high nutritional risk group was 58.8%. It took 5.00 (1.00, 8.00) d for the low nutritional risk group and 9.00 (3.00, 12.50) d for the high nutritional risk group to reach the energy standard. There was no statistical difference in the nutritional support methods, the time period before nutritional support, and energy supply conditions between the two groups. The mechanical ventilation time of the high nutritional risk group was 5.00 (1.50, 12.50) d, longer than that of the low nutritional risk group (P=0.018). The 28-day mortality rate of the high nutritional risk group was 47.7%, higher than that of the low nutritional risk group (P=0.001). There was no statistical difference in ICU stay between the two groups.

    Conclusion

    ·mNUTRIC score can be used to evaluate nutritional risk and predict the clinical prognosis of critically ill elderly patients. It is suggested that stratified clinical nutrition management should be carried out for the critically ill elderly patients with different nutritional risks. Critically ill elderly patients can benefit from personalized nutritional support programs, and the clinical prognosis of patients may be improved.

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    Influences of oral administration of probiotics on postoperative infection and liver function recovery in patients with partial hepatectomy
    Yi WU, Fang FANG, Hao HUANG, Ying CHEN
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (1): 9-15.   DOI: 10.3969/j.issn.1674-8115.2022.01.002
    Abstract68)   HTML11)    PDF(pc) (942KB)(293)       Save
    Objective

    ·To investigate the influences of oral administration of probiotics on postoperative infection and liver function recovery in patients with partial hepatectomy.

    Methods

    ·A total of 165 patients undergoing partial hepatectomy in Shanghai General Hospital, Shanghai Jiao Tong University, were involved in this prospective randomized control study. In accordance with the random number table, patients were divided into mechanical bowel preparation group (MBP group, n=55), non-bowel preparation group (NBP group, n=55) and probiotics bowel preparation group (PBP group, n=55). Patients' general information, postoperative fever, the first time of flatus and defecation, and infectious indexes and liver function indexes on the 1st,3rd and 5th day after operation were collected and compared among the groups.

    Results

    ·There was no significant difference in the basic data among the 3 groups (all P>0.05). On the 5th day after operation, the white blood count of the PBP group was significantly lower than that of the MBP group (P=0.012) and NBP group (P=0.029). The level of glutamic-pyruvic transaminase of the PBP group was significantly lower than that of the MBP group and NBP group on the 3rd day (P=0.040, P=0.036) and the 5th day (P=0.002, P=0.019) after operation.

    Conclusion

    ·Oral probiotics intestinal preparation is helpful to reduce infection after partial hepatectomy and accelerate the recovery of liver function.

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    Study on the correlation between the expression of miR-146a-5p and the severity of intestinal injury in neonatal necrotizing enterocolitis
    Jiang-long CHEN, Tong CHEN, Zhi-bao LÜ, Xue-li WANG, Qing-feng SHENG
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2021, 41 (9): 1147-1153.   DOI: 10.3969/j.issn.1674-8115.2021.09.003
    Abstract121)      PDF(pc) (5829KB)(291)       Save
    Objective

    ·To detect the expression level of miR-146a-5p in the intestinal tract of neonatal necrotizing enterocolitis (NEC), and analyze its correlation with the severity of intestinal injury in children with NEC.

    Methods

    ·The clinical data of children with NEC and intestinal atresia (IA) admitted to the Department of General Surgery of Shanghai Children's Hospital, Shanghai Jiao Tong University from January 2014 to December 2018 were collected, respectively. According to the location of intestinal tissue samples, children with NEC were divided into NEC-inflamed group and NEC-unaffected group. The intestinal tissue samples of children with IA were used as control group (i.e. IA group). Newborn C57BL/6J mice aged 5-7 days were randomly divided into NEC model group and control group. The former group was treated by modeling, while the latter was not. After the mice were killed, the terminal ileum tissue samples were taken. Hematoxylin-eosin staining was performed on the tissue samples of newborn mice and children in each group, and histopathological grade of mice was performed. The expression level of miR-146a-5p in the intestine of the newborn mice and the children in each group were detected by in situ hybridization, and the differences of expression between the two groups were compared, respectively. The correlation between the expression level of miR-146a-5p and histopathological grade in intestinal tract of children with NEC was analyzed. The distribution of children with miR-146a-5p high expression (positive cells≥100) and low expression (positive cells <100) in different clinical data was compared.

    Results

    ·① Compared with the control group, the pathological grade and the expression level of miR-146a-5p (P=0.000) in the terminal ileum of NEC model mice were higher. ② Compared with IA group and NEC-unaffected group, the expression level of miR-146a-5p was higher in NEC-inflamed group (both P=0.000). And the expression level of miR-146a-5p was positively correlated with the pathological grade of intestinal tissues in children with NEC (P=0.015, r=0.578). ③ Compared with miR-146a-5p low expression, the number of children with intestinal resection length ≥5 cm in miR-146a-5p high expression was more (P=0.005).

    Conclusion

    ·The high expression of miR-146a-5p is related to the severity of intestinal injury in NEC, suggesting that miR-146a-5p is involved in the occurrence and development of NEC.

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    Relationship between preoperative glycosylated hemoglobin and postoperative delirium in patients following off-pump coronary artery bypass grafting
    Ye HE, Fang FANG
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (1): 21-27.   DOI: 10.3969/j.issn.1674-8115.2022.01.004
    Abstract60)   HTML8)    PDF(pc) (1071KB)(288)       Save
    Objective

    ·To investigate the relationship between postoperative delirium and preoperative HbA1c in patients with off-pump coronary artery bypass grafting (OPCAB), so as to provide reference for further intervention.

    Methods

    ·A prospective study was used to collect 364 surgical patients admitted to the Department of Cardiac Surgery in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine. The data were collected through the general information questionnaire and the simple mental status assessment scale, and the Confusion Assessment Method of Intensive Care Unit, and Chinese Version of 3-minute Diagnostic Confusion Assessment Method were used to assess postoperative delirium. Univariate analysis was used to screen out the risk factors for delirium with P<0.05, and then a multi-factor Logistic regression analysis was used. The generalized additive model was used to observe the dynamic changes of HbA1c and the incidence of postoperative delirium, and the receiver operating characteristic (ROC) curve was drawn to clarify the boundary value.

    Results

    ·The influencing factors of postoperative delirium in OPCAB patients were age, alcohol use, peripheral vascular disease, NYHA function classification, LVEF, albumin, HbA1c, intraoperative blood transfusion, acid-base imbalance, and electrolyte imbalance. The generalized additive model and multivariate Logistic regression analysis showed that the higher the preoperative HbA1c, the higher the incidence of postoperative delirium in OPCAB patients.Through ROC curve analysis, it was determined that when the HbA1c>6.45%, the risk of delirium after OPCAB increased accordingly.

    Conclusion

    ·For patients undergoing OPCAB surgery, HbA1c is an independent risk factor for postoperative delirium. With the increase of HbA1c, the incidence of delirium gradually increases, suggesting that the preoperative HbA1c of OPCAB patients should be maintained at a normal level.

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    Development of knowledge-attitude-practice questionnaire for mechanical prophylaxis of deep venous thrombosis and its reliability and validity testing
    Chunhong HAN, Jie WANG, Yang HONG, Yahui TONG
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (1): 28-35.   DOI: 10.3969/j.issn.1674-8115.2022.01.005
    Abstract60)   HTML6)    PDF(pc) (950KB)(278)       Save
    Objective

    ·To develop a knowledge-attitude-practice questionnaire for mechanical prophylaxis of deep venous thrombosis for orthopedic nurses in China, and analyze its reliability and validity.

    Methods

    ·On the basis of literature review, combined with the characteristics of orthopedic diseases and orthopedic nurses, a preliminary questionnaire for mechanical prophylaxis of deep venous thrombosis was prepared. In January 2020, two rounds of expert letter consultation were conducted to demonstrate and modify the items in the first draft and form the test version of the questionnaire for mechanical prophylaxis of deep vein thrombosis.In March 2020, tests were conducted among 620 orthopedic nurses from 36 medical units in 13 cities in Jiangsu Province. Item analysis was carried out with critical ratio method and homogeneity test. Reliability analysis was carried out from internal consistency reliability, split-half reliability and retest reliability. Validity was analyzed from content validity and structure validity.

    Results

    ·The first draft of the questionnaire contained 37 items; after the first round of expert consultation, 4 items were revised and 7 items were added; after the second round of expert consultation, a test version of the questionnaire containing 44 items was formed. A total of 620 questionnaires were distributed. The effective recovery rate of the questionnaire was 96.77%. The critical ratio method showed that the item decision values t, which reflected the t-test results of independent samples of high and low groups, ranged from 5.89 to 20.31, and the difference was statistically significant (all P<0.05). The homogeneity test showed that Pearson correlation coefficient r, which reflected the correlation between the score of each item and the total score of the scale, ranged from 0.49 to 0.79, and the difference was statistically significant (all P<0.05). Therefore, 44 items were retained after item analysis. The Cronbach's α coefficient reflecting the internal consistency of the total questionnaire was 0.893, the Spearman-Brown coefficient reflecting the half-fold reliability was 0.794, and the intraclass correlation coefficient reflecting the retest reliability was 0.909. The scale-level content validity index reflecting content validity was 0.926 and the item-level content validity index was 0.833?1. Kaiser-Meyer-Olkin measure of sampling adequacy and Bartlett's sphericity test chi-square value which reflected the structure validity were 0.883 and 12 560.176 (df=666, P<0.05) respectively. These values indicated that the questionnaire was suitable for exploratory factor analysis. In addition, 7 items were deleted according to the absolute value of factor load. Finally, 37 items remained. Seven common factors with eigenvalue greater than 1 were extracted. The 7 common factors were named the act of mechanical prophylaxis, risk perception of mechanical prophylaxis, indications of mechanical prophylaxis, contraindications of mechanical prophylaxis, conceptual cognition of mechanical prophylaxis, mechanical preventive response and health education cognition of mechanical prophylaxis, respectively. The cumulative variance contribution rate was 61.992%.

    Conclusion

    ·The questionnaire in this study shows good reliability and validity. It can be used as an investigation tool to study the current attitude, knowledge and behavior of mechanical prophylaxis of orthopedic nurses.

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    Inhibitory effect of sanguinarine on proliferaton and invasion of gastric cancer cells by upregulating m 6A methyltransferase 14
    Ming CHEN, Jing ZHANG
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (2): 135-141.   DOI: 10.3969/j.issn.1674-8115.2022.02.001
    Abstract113)   HTML365)    PDF(pc) (2415KB)(238)       Save
    Objective

    ·To investigate the effect of sanguinarine (SAG) on the proliferation and invasion of gastric cancer cells MGC-803 and AGS, and the relationship between the mechanism and N6-methyladenosine (m6A) methyltransferase 14 (METTL14).

    Methods

    ·After the gastric cancer cell lines (MGC-803 and AGS) were exposed to different concentrations of SAG (0, 10, 20 μmol/L) for 48 h, quantitative PCR and Western blotting analysis were used to detect the effect of SAG on the expression of METTL14. Then, MGC-803 and AGS cells transfected with lentiviruses-mediated small interfering RNA of METTL14 (si-METTL14) or control (si-NC) were treated with 10 μmol/L SAG or PBS for 48 h, and thus the two cell lines were divided into si-METTL14+SAG group, si-NC+SAG group and si-NC+PBS group, respectively. Quantitative PCR and Western blotting were used to verify the expression levels of METTL14 after it was transfected with si-METTL14 in gastric cancer cells. The proliferation level, number of clones formed and invasion potential of the 3 groups in both MGC-803 cells and AGS cells were observed by MTT proliferation assay, cell clone formation test and Transwell invasion assay, respectively. Independent samples t test was used for comparison between two groups of data, and one-way ANOVA was used for comparison between more than two groups of data.

    Results

    ·Compared with the control group (0 μmol/L), 10 μmol/L SAG and 20 μmol/L SAG up-regulated METTL14 mRNA and protein expression levels (P<0.05), showing a certain concentration dependence. Quantitative PCR and Western blotting results confirmed that the expression levels of METTL14 in gastric cancer cells were significantly reduced after transfection of si-METTL14 in both MGC-803 cells and AGS cells. MTT cell proliferation assay showed that the cell proliferation rate of the si-NC+SAG group was significantly lower than that of the si-NC+PBS group in each cell line (P=0.000). The cell clone formation test showed that the number of cell clones of the si-NC+SAG group was significantly smaller than that of the si-NC+PBS group in each cell line (P<0.01). The Transwell invasion assay showed that the cells crossing Matrigel gel in the si-NC+SAG group was significantly less than that in the si-NC+PBS group in each cell line (P<0.01). si-METTL14 could partially reverse the inhibitory effects of SAG on gastric cancer cells.

    Conclusion

    ·SAG can inhibit the proliferation activity, clonal formation and invasion potential of gastric cancer cells, which may be realized by upregulating METTL14 expression level.

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    Analysis of clinicopathologic features and prognosis of eight children with granulosa cell tumor of ovary
    Zhengwen XING, Ying WU, Xueli WANG, Qingyu WANG, Wenting WANG, Zhi LI, Bin ZHANG, Jing JIN
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (2): 192-196.   DOI: 10.3969/j.issn.1674-8115.2022.02.009
    Abstract79)   HTML31)    PDF(pc) (3077KB)(188)       Save
    Objective

    ·To investigate the clinicopathological features and prognosis of ovarian granulosa cell tumor (GCT) in children.

    Methods

    ·The clinicopathologic and follow-up data of 8 patients with ovarian GCT in Shanghai Children's Hospital from June 2008 to June 2018 were collected and retrospectively studied to summarize the clinicopathological features and analyze the prognosis.

    Results

    ·The age of onset in this group ranged from 2 to 12 years with median age of 6.5 years. Two cases were adult granulosa cell tumor (AGCT) and six cases were juvenile granulosa cell tumor (JGCT). The first symptoms were abdominal pain or abdominal mass. Six patients were complicated with symptoms of precocious puberty, including 5 cases of true precocious puberty and 1 case of pseudo precocious puberty. The levels of peripheral blood sex hormones changed to varying degrees. Gross examination showed that the tumor masses ranged from 4 to 22 cm in the greatest dimension (average 12.8 cm). All of the 8 tumors were mixed solid-cystic in appearance. Under light microscope, AGCT showed obvious nuclear sulcus and microfollicular structure, containing eosinophilic substances, namely characteristic Call-Exner bodies. JGCT had follicular structures of different sizes, containing basophilic secretions. The inner layer of the follicular wall was composed of granular cells, which could be surrounded by follicular membrane cells. No Call-Exner bodies were found, and nuclear sulcus were rare. The results of immunohistochemistry showed that α-inhibin and CD99 were positive, and epithelial membrane antigen (EMA) were negative in all the cases. In 5 cases calretinin were positive, and in 5 cases cytokeratin (CK) were positive. Ki-67 proliferation index was 5%?50%. There were 3 estrogen receptor (ER) positive cases and 6 progesterone receptor (PR) positive cases. Forkhead transcription factor 2 (FOXL2) was highly expressed in 2 cases of AGCT and 6 cases of JGCT. SRY-box transcription factor 9 (SOX9) positive cells were scattered in 2 cases of AGCT and 3 cases of JGCT. All the cases were treated with standard surgery. Tumor rupture or metastasis was found in 5 cases, and ascites was suspiciously positive in 1 case. Eight children with ovarian GCT were followed up for 19?155 months, and all of them survived in good health.

    Conclusion

    ·The clinical features of AGCT and JGCT in children's ovaries are similar and have typical histopathological features respectively. The selection of suitable immunohistochemical detection method is helpful for differential diagnosis of ovarian tumors in children. The prognosis of ovarian GCT in children is good even with tumor rupture after radical surgery.

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    Interventional effects of nicotinamide mononucleotide on metabolism in aging mice
    Guodong DANG, Xinyu HONG, Meiqin CAI
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (2): 158-165.   DOI: 10.3969/j.issn.1674-8115.2022.02.004
    Abstract98)   HTML28)    PDF(pc) (1837KB)(186)       Save
    Objective

    ·To investigate the effects of nicotinamide mononucleotide (NMN) on metabolism in aging mice.

    Methods

    ·Seventy C57BL/6N male mice were randomly divided into 5 groups by using a table of random numbers. They were the control group, the premature aging model group, the aging model group, the intervention group Ⅰand the intervention group Ⅱ. Each group contained 14 mice. Except the control group, D-galactose (D-gal) (150 mg/kg) was subcutaneously injected into the napes of mice in the other 4 groups to establish the aging model of mice. NMN (300 mg/kg) was given to the intervention group Ⅰ and the intervention group Ⅱ by intragastric administration at the same time, and the other groups were given the same amount of distilled water, once a day, for 6 weeks in the premature aging model group and the intervention group Ⅰ, and for 12 weeks in the aging model group and the intervention group Ⅱ. The control group was given the same amount of normal saline and distilled water, once a day, for 6 weeks. Six weeks after modeling, the energy metabolism levels of the mice in the control group, the premature aging model group and the intervention group Ⅰ were detected, including respiratory metabolism, activity level and energy consumption. The organ indexes of thymus, spleen, liver and kidney were calculated. The glucose tolerance and insulin sensitivity were measured. In addition, the content of superoxide dismutase (SOD) and the activities of glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) in the serum and liver tissue were detected. Twelve weeks after modeling, the above indexes were detected in the aging model group and the intervention group Ⅱ.

    Results

    ·Compared with the control group, the thymus index (P=0.035, P=0.000) and renal index (P=0.009, P=0.002) of the model groups were significantly decreased. The O2 consumption (P=0.018, P=0.000), CO2 exhalation (P=0.044, P=0.003), energy consumption (P=0.010, P=0.001) and activity ability (both P=0.000) of the premature aging model group and the aging model group were significantly decreased at night. The insulin sensitivity was significantly reduced (P=0.012, P=0.011). The activities of SOD (P=0.002, P=0.001) and GSH-Px (P=0.001, P=0.011) in serum were significantly decreased and the content of MDA in serum was significantly increased (both P=0.000). The decline of energy metabolism levels, thymus and kidney indexes and antioxidant index verified the success of D-gal aging model. Compared with the premature aging model group, the intervention group Ⅰ had no significant difference in respiratory metabolism, energy consumption, glucose tolerance, insulin sensitivity and other indicators (all P>0.05). But in the intervention group Ⅰ, the activity ability was significantly improved (P=0.022), the activities of SOD (P=0.026) and GSH-Px (P=0.006) in serum were significantly increased, and the MDA content in serum was significantly decreased (P=0.011). Compared with the aging model group, the O2 consumption (P=0.045), CO2 exhalation (P=0.030), activity ability (P=0.049) and energy consumption (P=0.043) in the intervention group Ⅱ were significantly increased at night. Compared with the aging model group, the impaired glucose tolerance was improved (P=0.030), the insulin sensitivity was increased (P=0.010)in the intervention group Ⅱ, the activity of SOD in serum was significantly increased (P=0.046), and the MDA content in serum and liver tissue was significantly decreased (P=0.000). There was no significant difference in the activity of GSH-Px in serum and liver tissue between the two groups (P>0.05).

    Conclusion

    ·NMN can improve the metabolic level of aging mice to a certain extent, and its mechanism may be related to improving the antioxidant capacity of the body.

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    Effects of Pcsk9 gene interference on high fat-induced nonalcoholic fatty liver disease with atherosclerosis in rats
    Xiaowen ZHANG, Yi WANG, Chan ZHANG, Di ZHANG, Hang YUN, Di HUANG
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (2): 150-157.   DOI: 10.3969/j.issn.1674-8115.2022.02.003
    Abstract84)   HTML239)    PDF(pc) (2405KB)(184)       Save
    Objective

    ·To investigate the effects of proprotein convertase subtilisin kexin 9 (Pcsk9) gene knockdown on non-alcoholic fatty liver disease (NAFLD) and atherosclerotic lesions in rats induced by high fat.

    Methods

    ·The SD rat model of NAFLD was established. Rats were randomly divided into 4 groups: control group, model group (high fat), shRNA-negative control (NC) interference model group (high fat+shRNA-NC) and Pcsk9-shRNA interference model group (high fat+ Pcsk9-shRNA). Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect Pcsk9 gene interference efficiency. Fasting serum insulin was determined by radioimmunoassay. Automatic biochemical analyzer was used to detect levels of blood lipid in rats. Hematoxylin-eosin staining (H-E staining) was used to observe the injury of liver tissue and aorta tissue. Apoptosis of liver tissue was detected by TUNEL staining. The levels of interleukin-1β (IL-1β), IL-6 and inducible nitric oxide synthase (iNOS) in peripheral blood were detected by enzyme linked immunosorbent assay (ELISA). The expression of PCSK9, Toll-like receptor 4 (TLR4), nuclear factor κB (NF-κB) P65 and tumor necrosis factor α (TNF-α) were detected by Western blotting.

    Results

    ·Compared with the control group, obesity index and insulin level in the model group were significantly increased (all P=0.000); the apoptosis rate of liver cells was significantly increased (P=0.000); the level of high density lipoprotein cholesterol (HDL-C) was significantly decreased, while the levels of low density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and triacylglycerol (TAG) were significantly increased (all P=0.000); the levels of IL-1β, IL-6 and iNOS were significantly increased (all P=0.000); TLR4, NF-κB P65 protein activation and TNF-α expression were significantly increased (all P=0.000); the liver tissue and aorta tissue were significantly damaged. After interference of Pcsk9 gene expression, compared with the model group, obesity index and insulin level in the high fat+Pcsk9-shRNA group were significantly reduced (P=0.007, P=0.000); the apoptosis rate of liver cells was significantly reduced (P=0.000); the level of HDL-C was significantly increased while the levels of LDL-C, TC and TAG were significantly decreased (all P=0.000); the levels of IL-1β, IL-6 and iNOS were significantly decreased (all P=0.000); TLR4, NF-κB P65 protein activation and TNF-α expression were significantly decreased (all P=0.000); the histopathological lesions of liver tissue and aorta tissue were improved.

    Conclusion

    ·Knockdown of Pcsk9 gene can reduce obesity index, insulin level, blood lipid index and inflammatory response in the rats with NAFLD and atherosclerosis, and inhibit the activation of TLR4 and NF-κB P65 protein, thereby improving the injury of liver and aortic tissue in rats.

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    Application of three-dimensional electron microscopy to morphological study of neurons in brainstem cochlear nucleus
    Jialei ZHOU, Haibin SHENG, Haoyu WANG, Yan LU, Fangfang WANG, Hao WU, Yunfeng HUA
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (2): 142-149.   DOI: 10.3969/j.issn.1674-8115.2022.02.002
    Abstract73)   HTML356)    PDF(pc) (3073KB)(172)       Save
    Objective

    ·To explore the feasibility of cross-scale neuroanatomy and connectomics of mouse cochlear nucleus (CN) by using a new three-dimensional (3D) electron microscopic imaging method.

    Methods

    ·The intact CN was obtained after the brain tissue of adult CBA/Ca mice (2 months old) was fixed and dissected, stained with heavy metals (reducing osmium amplification method) , dehydrated with gradient ethanol and anhydrous acetone and embedded with low viscosity resin. The CN tissue was imaged by X-ray microscopy and 3D reconstruction, and its staining quality was evaluated. Then targeted subdivision was located according to the specific distribution of auditory nerve fibers. The low-resolution pre-scan of the CN tissue was performed by scanning electron microscopy, and compared with X-ray microscopic dataset. After the target location was determined, the volume of interest was mapped by serial block-face scanning electron microscopy (SBEM) for 3D reconstruction, and the ultrastructures of bushy cells and the synapses projecting on its surface were tracked, annotated and reconstructed.

    Results

    ·3D electron microscopic samples of intact CN of CBA/Ca mice were successfully prepared. The 3D structure of CN with cell resolution was collected and reconstructed by X-ray microscopic imaging, and the anatomical localization of subregions of CN was achieved. The 3D electron microscopic data of bushy cells in the target area of CN were successfully collected by SBEM. The tracking, labeling and reconstruction of endbulb of Held synapses and other non-auditory synapses on the cell body of target bushy cells were completed. The data of 3D electron microscopy showed that there were 5 endbulb of Held synapses projecting to the surface of the target bushy cell, forming a total of 348 synaptic active zones, while there were 97 synapses from non-auditory nerve.

    Conclusion

    ·It is feasible to prepare 3D electron microscopic samples of adult mouse intact CN by Osmium-based enbloc staining and resin embedding. X-ray microscopic imaging can be used for rapid and accurate localization of subregions and target volume of CN, and the acquired 3D electron microscopic data can be used to study the neuronal morphology and synaptic connections in the CN.

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    Establishment of a nomogram clinical scoring system for the risk of heterotopic ossification in patients undergoing surgery after fracture
    Yekai WANG, Wei CHEN, Yinghui YANG, Jingze WU, Heping WANG, Yanzhen YAO, Zhoujun BAO
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (2): 166-172.   DOI: 10.3969/j.issn.1674-8115.2022.02.005
    Abstract69)   HTML33)    PDF(pc) (1837KB)(168)       Save
    Objective

    ·To establish a nomogram scoring system to predict morbidity of heterotopic ossification (HO) in the patients undergoing surgery after fracture.

    Methods

    ·From August 2018 to October 2020, 124 patients with fractures from department of orthopaedics or brain surgery, including 81 males and 43 females with an average age of (56.48±15.45) years old (ranging from 25?91 years old), were enrolled in the study. Clinical features including gender, age, with brain trauma or not, anesthetic mode, operation duration time, and blood loss during operation were collected. Peripheral blood samples were collected at three time points, i.e. 1 d, 7 d and 15 d after fracture, and the sera levels of bone morphogenetic protein 2 (BMP-2), BMP-4, BMP-5, BMP-7, interleukin 4 (IL-4), IL-6, IL-10, interferon γ (IFN-γ), and transforming growth factor-β (TGF-β) were detected by ELISA. All the patients were divided into HO group and non-HO group according to follow-up outcomes. The variables with statistically significant differences (α=0.15) between the two groups selected from clinical and laboratory indications were included in the univariate Cox regression model. Then the variables selected from univariate Cox regression model (α=0.05) were incorporated into multivariate Cox regression model to screen the independent risk factors of HO and calculate the risk ratios (HR). Finally, the nomogram scoring system was output through rms package in R language.

    Results

    ·The follow-up observation found 13 HO cases after a median time of 71 (38, 292) d. Seven independent risk factors for HO, i.e. brain trauma (HR=2.932, P=0.038), operation duration time (HR=1.005, P=0.007), blood loss during operation (HR=1.004, P=0.022), BMP-2 (15d) (HR=1.009, P=0.044), BMP-4 (15 d) (HR=1.004, P=0.011), TGF-β (15 d) (HR=1.011, P=0.046), and BMP-7 (7 d) (HR=1.004, P=0.008), were selected by comparison between groups, univariate COX regression and multivariate COX regression sequentially. The nomogram to predict morbidity of HO after 90 d, 180 d, and 360 d was generated.

    Conclusion

    ·The seven scoring indexes of nomogram scoring system for predicting the risk of HO in the patients undergoing surgery after fracture are with brain trauma or not, operation duration time, blood loss during operation, levels of BMP-2, BMP-4 and TGF-β in peripheral blood 15 d after fracture and BMP-7 7 d after fracture.

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    Comparison of mismatch negativity in patients with schizophrenia and depression
    Meng-ting SHEN, Xuan-hong ZHANG, Zhen-ying QIAN, Hui LI, Jian-hua SHENG, Ji-jun WANG, Ying-ying TANG
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2021, 41 (8): 1041-1045.   DOI: 10.3969/j.issn.1674-8115.2021.08.007
    Abstract132)   HTML9)    PDF(pc) (1250KB)(167)       Save
    Objective

    ·To compare the difference of mismatch negativity (MMN) between first-episode schizophrenia and depression and its correlation with clinical characteristics, and explore the role of pre-attention processing in the mechanisms of schizophrenia and depression.

    Methods

    ·Twenty patients with schizophrenia and 19 patients with depression were selected in the outpatient department of Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine from January 2014 to December 2016. Healthy controls were also recruited. The Positive and Negative Syndrome Scale (PANSS) was used to measure the clinical symptoms of schizophrenia. Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA) were used to measure the clinical symptoms of depression. All patients and healthy controls completed MMN detection and clinical scale assessments. The amplitudes and latencies of duration MMN (DMMN) and frequency MMN (FMMN) were analyzed by repeated measures analysis of variance with group as the between-group factors. The midline electrodes (Fz, Fcz) were used as the with-in group factor; meanwhile, region (F, Fc) and laterality (1 for left, 2 for right) were used as the within-group factors for lateral electrodes and the factor sex was used as covariate. Partial correlations was performed to find the correlation between MMN and clinical characteristics.

    Results

    ·① The amplitude of DMMN in patients with schizophrenia 2 for [(-2.70±2.46) μV)] was lower than that in patients with depression [(-5.06±0.46) μV] and healthy controls [(-5.15±0.43) μV] (both P≤0.001). No significant group differences of DMMN latency were observed at midline or lateral electrodes (All P>0.05). ② There was no significant group difference of FMMN amplitudes at midline electrodes (P>0.05) but a significant between-group difference at lateral electrodes (P=0.040). No significant group differences of FMMN latency were observed at midline or lateral electrodes (All P>0.05). ③ There was a significant correlation between DMMN amplitudes at F2 (P=0.042) or Fz (P=0.032) and general scores of PANSS in schizophrenia patients. There was no correlation in depression patients.

    Conclusion

    ·Abnormality of DMMN exists in the patients with first episode schizophrenia but not in the patients with depression, suggesting that DMMN amplitudes may work as a biological marker to distinguish schizophrenia and depression.

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    Screening potential hub genes associated with myocardial ischemia-reperfusion injury in mice based on GEO database and bioinformatics analysis
    Jianru WANG, Guangcao PENG, Mingjun ZHU
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2022, 42 (1): 51-62.   DOI: 10.3969/j.issn.1674-8115.2022.01.008
    Abstract104)   HTML13)    PDF(pc) (8936KB)(157)       Save
    Objective

    ·To screen the potential hub genes associated with myocardial ischemia-reperfusion injury (MIRI) in mice by bioinformatics analysis based on gene expression omnibus (GEO) database.

    Methods

    ·The mouse MIRI data sets GSE61592, GSE83472 and GSE160516 were obtained from GEO database. The differentially expressed genes (DEGs) in each data set were screened by limma package, and then robust DEGs were screened by robust sorting integration (RRA) method. The protein-protein interaction (PPI) network of robust DEGs was constructed, and the submodules and hub genes in the PPI network were screened. The clusterProfiler package was used to analyze the robust DEGs, the most important submodule genes and hub genes by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Eighteen male C57BL/6 J mice aged 6?8 weeks were randomly divided into sham group and MIRI group, 9 mice each group. The MIRI model was constructed by left anterior descending coronary artery ligation for 30 min ischemia and 24 h reperfusion, and the mRNA expression of hub genes was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR).

    Results

    ·RRA method identified 294 robust DEGs in three data sets. In PPI network, a total of 14 sub-modules were screened, of which module 1 was the most important and 17 hub genes were found. GO and KEGG analysis showed that the robust DEGs, module 1 genes, and the hub genes were mainly involved in regulating the migration of inflammatory cells, the activity of chemokines and cytokines and their receptors, Toll-like receptors and other biological function and signaling pathways. RT-qPCR results showed that compared with the sham group, the expressions of chemokine (C-C motif) ligand 4 (Ccl4), Ccl6, Ccl7, chemokine (C-X-C motif) receptor 4 (Cxcr4), chemokine (C-C motif) receptor 2 (Ccr2), signal-regulatory protein β1 (Sirpb1), low affinity immunoglobulin gamma Fc region receptor Ⅱb (Fcgr2b), leukocyte surface antigen CD53 (Cd53), arachidonate 5-lipoxygenase activating protein (Alox5ap), myeloid differentiation primary response gene 88 (Myd88), macrophage scavenger receptor 1 (Msr1), matrix metallopeptidase 14 (Mmp14), triggering receptor expressed on myeloid cells 2 (Trem2) and leupaxin (Lpxn) were up-regulated in the myocardium of the MIRI group, but there was no difference in low affinity immunoglobulin gamma Fc region receptor Ⅲ (Fcgr3), complement C1q subcomponent subunit B (C1qb) and a disintegrin and metalloproteinase domain-containing protein 8 (Adam8). By reviewing the literatures, Trem2, Lpxn, Cd53, Alox5ap, Sirpb1 and Fcgr2b were not reported to participate in MIRI.

    Conclusion

    ·This study has unearthed 6 potential hub genes for MIRI in mice, and the results can provide new ideas and entry points for further exploring the molecular mechanism and therapeutic targets of MIRI.

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    Evaluation of JDBM porous scaffold coated with DCPD in promoting angiogenesis and repairing bone defects
    Qing WANG, Wei WANG, Da-jun JIANG, Wei-tao JIA
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2021, 41 (6): 732-740.   DOI: 10.3969/j.issn.1674-8115.2021.06.005
    Abstract114)   HTML16)    PDF(pc) (8449KB)(146)       Save
    Objective

    ·To evaluate the biological effects of JDBM (Mg-Nd-Zn-Zr) scaffold coated with DCPD (CaHPO4·2H2O) on angiogenesis and repairing bone defects in vivo and in vitro.

    Methods

    ·The JDBM-DCPD and JDBM-MgF2 scaffolds were constructed by using template replication method and chemical deposition method, and the characteristics of the scaffolds were observed by micro-CT and scan electron microscope. The bone marrow mesenchymal stem cells (BMSCs) were seeded on the scaffolds and the biocompatibility of scaffolds was evaluated by CCK-8 experiment and cell adhesion experiment. Transwell cell migration experiment and tube formation experiment were used to detect the effects of scaffold extracts on the migration and tube-forming ability of endothelial cell line Ea.hy926 cells, and immunofluorescence was used to further observe the secretion of vascular endothelial growth factor (VEGF). Alkaline phosphatase staining and alizarin red staining were used to detect the effect of the extracts on the osteogenic ability of BMSCs. Furthermore, the model of critical bone defect of femoral condyle was constructed in SD rats. The JDBM-DCPD and JDBM-MgF2 scaffolds were implanted into the defects, respectively, and the effects of scaffolds on the osteogenesis and vascularization were assessed by Microfil vascular perfusion, micro-CT scanning, and tissue section staining after 8 weeks of operation.

    Results

    ·The main spherical pore size of JDBM-DCPD scaffold was 400?450 μm and the calcium and phosphorus particles were evenly distributed on the pore wall with the size of 15?25 μm. BMSCs adhered and grew well on the surface of JDBM-DCPD scaffold. Compared with the control group and the JDBM-MgF2 scaffold extract, the JDBM-DCPD scaffold extract could significantly promote the migration, tube formation and VEGF expression of Ea.hy926 cells, and significantly enhance the early and late osteogenic differentiation of BMSCs in vitro. After 8 weeks of implantation, the JDBM-DCPD scaffold dramatically facilitated the regeneration of new bone and new vessels in the defect area compared with the JDBM-MgF2 scaffold.

    Conclusion

    ·The JDBM-DCPD scaffold exhibits excellent vascularization effects both in vivo and in vitro, especially early vascularization effect after implantation and bone regeneration promotion in vivo.

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    Review of immunosuppressive tumor microenvironment of pancreatic cancer
    Jing-wei LI, Li-wen WANG, Ling-xi JIANG, Qian ZHAN, Hao CHEN, Bai-yong SHEN
    JOURNAL OF SHANGHAI JIAOTONG UNIVERSITY (MEDICAL SCIENCE)    2021, 41 (8): 1103-1108.   DOI: 10.3969/j.issn.1674-8115.2021.08.018
    Abstract261)   HTML14)    PDF(pc) (908KB)(144)       Save

    Pancreatic cancer is a highly malignant tumor. The difficulty of early diagnosis and scarcity of effective clinical treatment strategies lead to poor prognosis. Tumor microenvironment (TME) of pancreatic cancer is composed of tumor cells, immune cells, stromal cells, extracellular matrix and soluble factors. TME plays an important role in the development, progression, invasion and metastasis of tumors. The pancreatic cancer microenvironment has significant immune cell infiltration, which is highly immunosuppressive. On the one hand, tumor cells edit the immune system so that cancer cells cannot be recognized by the immune system; on the other hand, they can recruit and activate various immunosuppressive cells such as pancreatic stellate cells, myeloid-derived inhibitory cells, tumor-associated macrophages, regulatory T cells and so on. These immunosuppressive cells can secrete immunosuppressive molecules, affect the function of anti-tumor immune cells, inhibit the host′s anti-tumor immune response, lead to tumor immune escape, and promote tumor development and metastasis. In this review, the mechanisms and effects of these immunosuppressive components are discussed and the updated results of immunotherapy on pancreatic cancer are studied, which may provide novel insights on TME and immunotherapy of pancreatic cancer.

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