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, Volume 50 Issue 3 Previous Issue    Next Issue
Inflammatory state and autism-like behavioral phenotype of offspring induced by maternal exposure to low-dose chemical mixtures during pregnancy in mice
SONG Linyang,WEN Wenzhi,LIU Jing,JIN Xiaobao,YANG Junhua
J Zhejiang Univ (Med Sci), 2021, 50(3): 279-289.   https://doi.org/10.3724/zdxbyxb-2021-0182
Abstract( 59 )   HTML( 16 )     PDF(2778KB)( 25 )

Objective:To investigate the effects of maternal exposure to 13 chemicals mixture (CM) during pregnancy on pregnancy outcome and health status of maternal/offspring mice. Methods:C57BL/6 pregnant mice were given drinking water containing carbaryl?0.0075?mg/kg, dimethoate?0.001?mg/kg, glyphosate?0.5?mg/kg, methomyl 0.0025?mg/kg, methyl parathion 0.003?mg/kg, triadimefon 0.03?mg/kg, aspartame 40?mg/kg, sodium benzoate?5?mg/kg, calcium disodium ethylene diamine tetra-acetate?2.5?mg/kg, ethylparaben 10?mg/kg, butylparaben 0.5?mg/kg, bisphenol A 0.004?mg/kg and acacia gum 34?mg/kg. The effects of CM exposure on pregnancy outcome, health status of dams/offspring, levels of circulating inflammatory cytokines in dams/offspring and emotional related behaviors of offspring were evaluated. Results: CM exposure during pregnancy had no significant effect on pregnancy outcome, liver function, body weight of the dams in late pregnancy and uterine/ovarian weight after delivery, however, it led to an increase in maternal serum IFN-γ level (P<0.05). CM exposure during pregnancy had no significant effect on the liver function of offspring, but increased the serum IFN-γ, prefrontal cortex IFN-γ, IL-6 and TNF-α and hippocampus IFN-γ levels in the offspring(allP<0.01). In addition, the offspring of CM group showed significant abnormal emotion-related (autism-like) behaviors in adulthood, especially in male offspring.Conclusion: Low dose CM exposure during pregnancy may induce inflammation status in dams/offspring, and lead to autism-like behaviors in offspring, indicating the potential effects of low dose CM exposure on human maternal and infant health.

Effect of operative trauma and multiple propofol anesthesia on neurodevelopment and cognitive function in developmental rats
LI Yang,LI Weiguang,FENG Zeguo,SONG Jie,ZHANG Chenggang,HUANG Lianjun,SONG Yanping
J Zhejiang Univ (Med Sci), 2021, 50(3): 290-297.   https://doi.org/10.3724/zdxbyxb-2021-0004
Abstract( 28 )   HTML( 2 )     PDF(6354KB)( 24 )

Objective: To investigate the effect of multiple propofol anesthesia and operative trauma on neuroinflammation and cognitive function in development rats and its mechanism. Methods:A total of 104 13-day-old neonatal Sprague-Dawley rats were randomly divided into 4 groups with 26 rats in each group: control group was treated with7.5?mL/kg saline q.d for 5?d, propofol group was treated with 75?mg/kg propofol q.d for 5?d,surgery group received abdominal surgery under local anesthesia and then treated with7.5?mL/kg saline q.d for 4?d, surgery with propofol group received 75?mg/kg propofol anesthesia plus abdominal surgery under local anesthesia with ropivacaine at d1, then treated with 75?mg/kg propofol q.d for 4?d. At d2 of experiment, 13 rats from each group were sacrificed and brain tissue samples were taken, the concentration of TNF-α in hippocampus was detected with ELISA, the expression of caspase-3 and c-fos in hippocampal tissue was determined with immunohistochemical method, the number of apoptotic neurons in hippocampus was examined with TUNEL assay. Morris water maze test was used to examine the cognitive function of the rest rats at the age of 60?d, and the TNF-α concentration, caspase-3, c-fos expressions and the number of apoptotic neurons in hippocampus were also detected. Results: Compared with control group, TNF-α concentration, caspase-3, c-fos expression and the neuroapoptosis in hippocampus increased significantly in other three groups (all P<0.05). Compared with surgery group, propofol group and surgery with propofol group showed increased TNF-α level, caspase-3 and c-fos expressions and apoptotic cell numbers (allP<0.05), but there was no significant difference between last two groups (allP>0.05). Morris water maze test showed that there were no significant differences in swimming speed, escape latency, target quadrant residence time and crossing times among groups (allP>0.05). TNF-α level, expressions of caspase-3 and c-fos and apoptotic cell numbers in hippocampus had no significant differences among the 4 adult rats groups (allP>0.05).Conclusion: Abdominal surgery and multiple propofol treatment can induce neuroinflammation and neuroapoptosis in hippocampus of neonatal rats, however, which may not cause adverse effects on neurodevelopment and cognitive function when they grown up.

Disorder of intestinal amino acid pathway in depression-like offspring rats induced by maternal separation
ZHANG Yurong,WANG Ruizhong,WANG Li,CHEN Rui
J Zhejiang Univ (Med Sci), 2021, 50(3): 298-304.   https://doi.org/10.3724/zdxbyxb-2021-0102
Abstract( 28 )   HTML( 6 )     PDF(2742KB)( 6 )

Objective: To investigate the intestinal amino acids pathway in depression-like offspring rats induced by maternal separation. Methods: Sprague-Dawley (SD) female rats were randomly divided into a control group (n=8) and a maternal separation group (n=8). After normal delivery, the maternal rats were separated from offsprings for 14 consecutive days and 3?h per day in maternal separation group; while rats in the control group was received no interventions in postpartum. Depression-like behaviors of offspring rats were evaluated using the sucrose preference test, novelty suppressed feeding test, and forced swimming test. Amino acid analyzer was used to detect the changes of amino acid contents in the small intestine, and the expressions of alanine-serine-cysteine transporter 2 (ASCT2), solute carrier superfamily 6 member 19 (B0AT1) and L-type amino acid transporter 1(LAT1) were detected by Western blot. Results:The weight of the offspring rats in the maternal separation group was significantly lower than that of the control group at 21 and 28?d (t=4.925 and 5.766, all P<0.01). Compared with the control group, the percentage of sucrose preference of the offspring rats in the maternal separation group was significantly reduced (t=2.709, P<0.05), and the feeding latency was significantly prolonged (t=–13.431, P<0.01). The immobility time in FST of maternal separation group was significantly longer (t=–3.616, P<0.01).Increased concentration of aspartic acid (t=–6.672, P<0.01) and down-regulation of glutamine (t=3.107, P<0.01) and glycine (t=9.781, P<0.01) were observed in maternal separation group. Western blot analysis revealed that the protein expressions of ASCT2 (t=6.734, P<0.01) and B0AT1 (t=9.015, P<0.01) in maternal separation group were reduced, while the expression of LAT1 was increased (t=–8.942, P<0.01).Conclusion: Maternal separation can induce the depression-like behavior in offspring rats; the amino acid contents and the amino acid transporter expression in the small intestine are reduced, which may be related to depression-like behavior induced by maternal separation.

Interventional effect of dietary fiber on blood glucose and pregnancy outcomes in patients with gestational diabetes mellitus
ZHANG Zhuangwei,LI Junqin,HU Tiantian,XU Chunjing,XIE Ni,CHEN Danqing
J Zhejiang Univ (Med Sci), 2021, 50(3): 305-312.   https://doi.org/10.3724/zdxbyxb-2021-0115
Abstract( 18 )   HTML( 0 )     PDF(2468KB)( 9 )

Objective: To investigate the effect of dietary fiber on blood glucose and pregnancy outcomes in patients with gestational diabetes mellitus (GDM). Methods: One hundred and twelve patients with GDM in the second trimester of pregnancy were recruited from Women’s Hospital, Zhejiang University School of Medicine. Patients were randomized into two groups with 56 in each group: the control group received basic nutrition support; while the dietary fiber group were given additional dietary fiber (9.5?g total dietary fiber per day) before meals in addition to basic nutrition support. Intervention for all cases lasted for 8 weeks. Fasting blood glucose and 2?h postprandial blood glucose (2 h BG) were measured every week, and oral glucose tolerance test (OGTT) was performed at 42 d postpartum to evaluate the glycemic outcomes. Perinatal outcomes were recorded. Results: The dietary fiber intervention markedly improved 2 h BG in patients with GDM and significantly elevated the glucose compliance rate from the 3rd to 8th week compared to the control group ( P<0.05 orP<0.01). OGTT 2 h glucose and the incidence of impaired glucose tolerance in the dietary fiber group were significantly lower than those in the control group, while the glucose compliance rate was significantly higher than that in the control group (allP<0.01). Moreover, the rates of adverse perinatal outcomes, such as premature rupture of membranes and neonatal hyperbilirubinemia were declined in the dietary fiber group (P<0.05 orP<0.01).Conclusion:Dietary fiber intervention can ameliorate hyperglycemia in GDM patients, improve perinatal outcomes and reduce the incidence of postpartum impaired glucose tolerance.

Relationship of abnormal mid-term oral glucose tolerance test and maternal weight gain with adverse pregnancy outcomes in women with gestational diabetes mellitus
CHEN Yunyan,WU Qi,ZHANG Lixia,CHEN Danqing,LIANG Zhaoxia
J Zhejiang Univ (Med Sci), 2021, 50(3): 313-319.   https://doi.org/10.3724/zdxbyxb-2020-0013
Abstract( 15 )   HTML( 1 )     PDF(2205KB)( 5 )

Objective: To explore the correlation of mid-term oral glucose tolerance test (OGTT) and maternal weight gain with adverse pregnancy outcomes in women with gestational diabetes mellitus (GDM). Methods: A total of 2611 pregnant women with GDM who were examined and delivered in Women’s Hospital, Zhejiang University School of Medicine from July 1st 2017 to 30th June 2018 were enrolled in this study. According to the number of abnormal items of mid-term OGTT results or maternal gestational weight gain (GWG), patients were classified. The incidence of adverse perinatal outcomes in each group and its relation with OGTT results and GWG were analyzed. Results: The incidence of gestational hypertension, premature delivery, macrosomia and large for gestational age infant (LGA) in three abnormal items GDM patients were significantly higher than those in one or two abnormal items GDM patients (all P<0.017). The incidence of gestational hypertension and premature delivery in two abnormal items GDM patients were higher than those in one abnormal item GDM patients (allP<0.017). The incidence of gestational hypertension and macrosomia in excessive GWG patients were significantly higher than those in inadequate and appropriate GWG patients (allP<0.017), and the incidence of LGA were higher than that in inadequate GWG patients (allP<0.017). The incidence of premature delivery and low birth weight infants in appropriate GWG patients were significantly lower than those in inadequate and excessive GWG patients, and the incidence of small for gestational age infant (SGA) were significantly lower than that in inadequate GWG patients (allP<0.017). In one abnormal item GDM patients, inadequate GWG was a risk factor for premature delivery and SGA (aOR=1.66, 95%CI: 1.10–2.52; aOR=2.20, 95%CI: 1.07–4.53), and protective factor for LGA (aOR=0.40, 95%CI: 0.27–0.59). And excessive GWG was a risk factor for gestational hypertension, premature delivery and low birth weight infants (aOR=2.15, 95%CI: 1.35–3.41; aOR=1.80, 95%CI: 1.20–2.72; aOR=2.18, 95%CI: 1.10–4.30).In two abnormal items GDM patients, inadequate GWG was a protective factor for macrosomia and LGA (aOR=0.24, 95%CI: 0.09–0.67; aOR=0.54, 95%CI: 0.34–0.86), while excessive GWG was risk factor for premature delivery (aOR=1.98, 95%CI: 1.23–3.18).In three abnormal items GDM patients, there was no significant relationship between GWG and adverse pregnancy outcomes. Conclusion: For GDM women with one or two items of elevated blood glucose in OGTT, reasonable weight management during pregnancy can reduce the occurrence of adverse pregnancy outcomes. For those with three items of elevated blood glucose in OGTT, more strict blood glucose monitoring and active intervention measures should be taken in addition to weight management during pregnancy.

Impact of pre-pregnancy body mass index, weight gain and blood lipid level during pregnancy on pregnancy outcome in patients with gestational diabetes mellitus
XU Heng,MA Yan,ZHANG Lixia,LIANG Zhaoxia,CHEN Danqing
J Zhejiang Univ (Med Sci), 2021, 50(3): 320-328.   https://doi.org/10.3724/zdxbyxb-2021-0185
Abstract( 16 )   HTML( 1 )     PDF(2231KB)( 7 )

Objective:To explore the effects of pre-pregnancy body mass index (BMI), weight gain and blood lipid level during pregnancy on pregnancy outcome in patients with and without gestational diabetes mellitus(GDM). Methods:A total of 12 650 singleton pregnant women without history of hypertension and diabetes who were admitted at Women’s Hospital, Zhejiang University School of Medicine for delivery from January 2018 to April 2019 were enrolled in the study. There were 2381 cases complicated with gestational diabetes (GDM group) and 10 269 cases without GDM (non-GDM group). The pre-pregnancy BMI and weight gain during pregnancy were documented in two groups. The factors related to perinatal outcome were analyzed. Results: In both GDM and non-GDM pregnant women, pre-pregnancy overweight and excessive weight gain during pregnancy were independent factors of large for gestational age infant (LGA), small for gestational age infant (SGA) and first cesarean section (P<0.01 orP<0.05). Excessive weight gain during pregnancy was also an independent risk factor of preeclampsia (P<0.05). Triglyceride levels in the second trimester were independently associated with multiple adverse pregnancy outcomes, such as LGA, preeclampsia, initial cesarean delivery, premature delivery.Conclusions: Controlling excessive or insufficient weight gain during pregnancy can significantly reduce the incidence of LGA and SGA. And controlling BMI before pregnancy can effectively reduce the incidence of LGA, preeclampsia and the first cesarean section. For non-GDM pregnant women, abnormal blood lipid levels in the second trimester may be closely related to multiple adverse pregnancy outcomes, and active dietary guidance or treatment is also required.

Impact of family history of diabetes on blood glucose, lipid levels and perinatal outcomes in pregnant women with gestational diabetes mellitus
ZHOU Yumei,XIE Ni,ZHANG Lixia,CHEN Danqing
J Zhejiang Univ (Med Sci), 2021, 50(3): 329-334.   https://doi.org/10.3724/zdxbyxb-2021-0193
Abstract( 25 )   HTML( 1 )     PDF(2153KB)( 12 )

Objective: To investigate the impact of family history of diabetes (FHD) on blood glucose, lipid levels and perinatal outcomes in pregnant women with gestational diabetes mellitus (GDM). Methods:A total of 1265 GDM women who gave childbirth in Women’s Hospital, Zhejiang University School of Medicine during January to December 2019 were enrolled in the study, including 253 women with FHD and 1012 women without FHD. The t-test or χ2 test were used to compare the blood lipid, blood glucose levels and perinatal outcomes including large for gestational age infant, small for gestational age infant, macrosomia, cesarean delivery, preeclampsia, preterm labor, postpartum hemorrhage, fetal distress. The correlation between FHD and perinatal outcomes were estimated by Logistic regression analysis. Results: The high density lipoprotein level at third-trimester was significantly lower in GDM women with FHD (P<0.05); and the women with FHD also had higher fasting blood glucose oral glucose tolerance test (OGTT)1?h, OGTT?2?h and glycosylated hemoglobin level (allP<0.01). In GDM women, FHD was an independent risk factor for preeclampsia (OR=3.27, 95%CI: 1.39–7.68).Conclusions: GDM women with FHD have lower high density lipoprotein and higher glucose levels. FHD is an independent risk factor for preeclampsia in GDM women.

Advances in the role of silence information regulator family in pathological pregnancy
GE Yingzhou,LIU Xinmei,HUANG Hefeng
J Zhejiang Univ (Med Sci), 2021, 50(3): 335-344.   https://doi.org/10.3724/zdxbyxb-2021-0183
Abstract( 17 )   HTML( 0 )     PDF(2425KB)( 3 )

Aberrant maternal inflammation and oxidative stress are the two main mechanisms of pathological pregnancy. The silence information regulator (sirtuin) family is a highly conserved family of nicotinamide adenine dinucleotide (NAD)-dependent deacylases. By regulating the post-translational modification of proteins, sirtuin is involved in various biological processes including oxidative stress and inflammation. Nowadays, emerging evidence indicates that sirtuin may be closely related to the occurrence and development of pathological pregnancy. The down-regulation of sirtuin can cause spontaneous preterm delivery by promoting uterine contraction and rupture of fetal membranes, cause gestational diabetes mellitus through promoting oxidative stress and affecting the activity of key enzymes in glucose metabolism, cause preeclampsia by reducing the proliferation and invasion ability of trophoblasts, cause intrahepatic cholestasis of pregnancy by promoting the production of bile acids and T helper 1 cell (Th1) cytokines, and cause intrauterine growth restriction through inducing mitochondrial dysfunction. Moreover, the expression and activation of sirtuin can be modulated through dietary interventions, thus sirtuin is expected to become a new target for the prevention and treatment of pregnancy complications. This article reviews the role of the sirtuin family in the occurrence and development of pathological pregnancy and its influence on the development of the offspring.

Relationship of biofilm-forming ability of Pseudomonas aeruginosa with swimming motility, twitching motility and virulence gene distribution
SHUI Jian,WANG Haichen,TAO Xiaoyan,MIN Changhang,LI Jun,ZOU Mingxiang
J Zhejiang Univ (Med Sci), 2021, 50(3): 345-351.   https://doi.org/10.3724/zdxbyxb-2021-0187
Abstract( 18 )   HTML( 2 )     PDF(5921KB)( 33 )

Objective:To investigate the relationship of biofilm-forming ability of Pseudomonas aeruginosa(PA) with swimming motility, twitching motility and virulence gene distribution. Methods:A total of 192 clinical isolates of PA were collected consecutively. Microtiter plate method was used to evaluate the ability to form biofilm. The swimming and twitching motilities were detected by plate method. Polymerase chain reaction (PCR) was used to detect virulence genes. Results:Of the 192 PA clinical isolates, 186 (96.9%) showed biofilm-forming ability. Among them, 36 isolates showed weak biofilm-forming ability, 84 exhibited moderate biofilm-forming ability and 66 showed strong biofilm-forming ability. The diameters of the swimming ring for PA with none biofilm-forming ability, weak biofilm-forming ability, moderate biofilm-forming ability, strong biofilm-forming ability were (9.12±6.76), (18.42±7.51), (19.10±4.77) and (17.80±5.27)?mm, respectively. The diameters of the twitching ring for PA in above groups were (8.38±1.50), (17.21±7.42), (18.49±5.62) and (20.44±6.43)?mm, respectively. The swimming motility and twitching motility of none biofilm-forming ability group were weaker than biofilm-forming ability groups (all P<0.05). Among 192 PA strains, 163 wereexoS positive (84.9%), 40 were exoUpositive (20.8%), 183 were exoY positive (95.3%), and 189 were exoT positive (98.4%). The positive rate of PA virulence gene exoS, exoU and exoT were different in strains with different biofilm-forming abilities (P<0.05). The rate ofexoS in the strong biofilm-forming ability group was lower than that in the moderate biofilm-forming ability group (χ2=9.293, P<0.01) and the weak biofilm-forming ability group (χ2=9.997, P<0.01). The rate ofexoU in the strong biofilm-forming ability group was higher than that in the weak biofilm-forming ability group (χ2=10.803, P<0.01).Conclusions:Most clinical isolates of PA can form biofilm. Swimming and twitching motilities are related to the formation of biofilm, but not significantly related to strength of biofilm-forming ability. The virulence genes of type Ⅲ secretion system for PA may be related to the biofilm-forming ability.

Salt-inducible kinase 2 regulates energy metabolism in rats with cerebral ischemia-reperfusion
ZHANG Ran,LIU Yun,ZHANG Cui,MA Mengyao,LI Shu,HONG Yun
J Zhejiang Univ (Med Sci), 2021, 50(3): 352-360.   https://doi.org/10.3724/zdxbyxb-2021-0164
Abstract( 21 )   HTML( 1 )     PDF(14685KB)( 7 )

Objective:To investigate the effects of salt-inducible kinase 2 (SIK2) on energy metabolism in rats with cerebral ischemia-reperfusion. Methods: Adult SD male rats (240-260?g) were divided into 5 groups: sham group, ischemia group, reperfusion group, adenovirus no-load group, and SIK2 overexpression group with 5 animals in each group. The middle cerebral artery occlusion (MCAO) was induced with the modified Zea-Longa line thrombus method to establish the cerebral ischemia reperfusion model. Eight days before the MCAO, SIK2 overexpression was induced by injecting 7 μL adenovirus in the right ventricle, then MCAO was performed for 2?h, followed by reperfusion 24?h. HE staining was used to observe the pathological changes of cerebral tissue in rats; TTC staining was used to observe the volume of cerebral infarct. The levels of adenosine triphosphate (ATP) and adenosine diphosphate (ADP) in rat brain tissue were detected by ELISA; the levels of SIK2 and hypoxia-inducible factor 1α (HIF-1α) in the rat brain tissues were detected by RT-qPCR and Western blotting. Results:Compared with the sham group, SIK2 level was decreased in the ischemia group, and it was further declined in the reperfusion group (P<0.05). Compared with the sham group and ischemic group, the pathological injury in reperfusion group were more severe, and the infarct size was larger; compared with the reperfusion group and adenovirus no-load group, the pathological injury of the SIK2 overexpression group was milder, and the infarct size is less. Compared with the sharn group, HIF-1α was increased in both ischemia group and reperfusion group, especially in ischemia group (allP<0.05); HIF-1α level in the SIK2 overexpression group was higher than that in the reperfusion group and adenovirus no-load group (allP<0.05). ATP level in ischemia group and reperfusion group was lower than that in the sham group, and the reperfusion group decreased more significantly than the ischemia group (P<0.05); ADP content was increased in the ischemia and reperfusion group, and the ADP content in reperfusion group was significantly higher than that in the ischemia group (P<0.05). ATP level in the SIK2 overexpression group was higher than that in the reperfusion group and adenovirus no-load group (allP<0.05), and ADP was decreased in the SIK2 overexpression group (allP<0.05).Conclusion:SIK2 can up-regulate the ATP level and down-regulate the ADP level in rat brain tissue and alleviate cerebral ischemia-reperfusion injury by increase the level of HIF-1α.

Effect of electro-acupuncture therapy on limb spasm and excitability of motor neurons in stroke rats
LIU Junxia,ZHAO Guigui,NIU Yan,GAN Ting,YAN Zhenyu,ZHANG Yasu
J Zhejiang Univ (Med Sci), 2021, 50(3): 361-368.   https://doi.org/10.3724/zdxbyxb-2021-0007
Abstract( 13 )   HTML( 0 )     PDF(4514KB)( 2 )

Objective:To investigate the effect of electro-acupuncture therapy on limb spasm and excitability of motor neurons in stroke rats. Methods:Ischemic stroke model was induced with middle cerebral artery embolization in SD rats. Thirty-three modeled rats were randomly divided into model group, electro-acupuncture group, and baclofen group with 11 rats in each group, and another 10 rats were taken as sham operation group. The electro-acupuncture group and the baclofen group were treated with electro-acupuncture and baclofen tablets respectively. The model group and the sham operation group had no intervention. The neural function was evaluated with Bederson’s scale and balance beam test; the muscle tension was measured with electrophysiography; the pathological changes of brain tissue was examined with HE staining; the content of glutamic acid (Glu) and γ-aminobutyric acid (GABA) in rat cerebral cortex was analyze with enzyme linked immunosorbent assay (ELISA) method, the expression of metabotropic glutamate receptor 1a (Grm1a) and γ-aminobutyric acid type B receptor subunit 1 (Gabbr1) mRNA were detected with RT-qPCR. Results:Compared with the model group, the neurological function scores of the electro-acupuncture group and the baclofen group showed a downward trend at d7 after operation (all P>0.05), and the neurological function scores of the electro-acupuncture group and the baclofen group were significantly decreased at d12 after the operation (allP<0.05). Compared with sham operation group, the electrophysiological results of model group, electro-acupuncture group and baclofen group were significantly lower (allP<0.05), and there was no statistical difference in the electrophysiological results of the model group, electro-acupuncture group and baclofen group at d7 after operation (allP>0.05). Compared with the model group, the electrophysiological results of the electro-acupuncture group and baclofen group were significantly increased 12?d after operation (allP<0.05). The results of HE staining showed that there was no cell edema and degeneration in the sham operation group, no pyknosis of the nucleus, and no bleeding in the interstitium. Cell edema and degeneration and mesenchymal congestion appeared in the model group. Compared with the model group, the cytoplasmic edema and degeneration and the interstitial bleeding in the electroacupuncture group and the baclofen group were reduced. Compared with sham operation group, the Glu content and the relative expression ofGrm1a mRNA was increased in the model group, electro-acupuncture group and baclofen group, while the GABA content and the relative expression of Gabbr1 mRNA decreased (all P<0.05). Compared with model group, the Glu content and the relative expression ofGrm1a mRNA in the electro-acupuncture group and baclofen group decreased, and the GABA content and relative expression of Gabbr1 mRNA increased (all P<0.05).Conclusion:Electro-acupuncture may improve limb spasm after stroke through regulating the expression of Glu and GABA in the cerebral cortex and the excitability of motor neurons in rats.

Development of a nomogram for predicting survival of patients with ovarian serous cystadenocarcinoma after surgery based on SEER database
CHEN Xiaobin,GUO Tingting
J Zhejiang Univ (Med Sci), 2021, 50(3): 369-374.   https://doi.org/10.3724/zdxbyxb-2021-0188
Abstract( 18 )   HTML( 1 )     PDF(2623KB)( 7 )

Objective:To develop a survival time prediction model for patients with ovarian serous cystadenocarcinoma after surgery.Methods:A retrospective analysis of 5906 postoperative patients with ovarian serous cystadenocarcinoma in the surveillance, epidemiology, and end results (SEER) database from 2010 to 2015 was performed. The independent risk factors for long-term survival were analyzed with multivariate Cox proportional hazard regression model. The nomogram of 3-year and 5-year survival was developed by using R language. The receiver operator characteristic (ROC) curve and C-index were used to test the discrimination of the model and the calibration diagram was used to evaluate the degree of calibration of the prediction model. The survival curves was conducted by the risk factors. Results: Cox proportional hazard regression model showed that age, race, histological grade (poorly differentiated and undifferentiated), stage T (T2a, T2b, T2c, T3a, T3b and T3c), and stage M (M1) were independent factors for the prognosis of patients with ovarian serous cystadenocarcinoma after surgery. A nomogram was developed by the R language tool for predicting the 3-year and 5-year survival of patients through age, race, histological classification, stage T and stage M. The C-index was 0.688 and the areas under ROC curve of the nomogram for predicting 3-year and 5-year survival were 0.708 and 0.716, respectively. The results of the calibration indicated that the predicted values were consistent with the actual values in the prediction models. The survival time of patients with high-risk factors was shorter than that of patients with low-risk factors (P<0.05).Conclusion:The developed nomogram in this study can be used to predict 3-year and 5-year survival of postoperative patients with ovarian serous cystadenocarcinoma, and it may be beneficial to guide clinical treatment.

Whether early stage pancreatic ductal adenocarcinoma patients could benefit from the post-operation chemotherapy regimens: a SEER-based propensity score matching study
SHI Jinbo,LI Xiawei,WU Yulian
J Zhejiang Univ (Med Sci), 2021, 50(3): 375-382.   https://doi.org/10.3724/zdxbyxb-2021-0194
Abstract( 14 )   HTML( 4 )     PDF(2869KB)( 8 )

Objective:To investigate whether chemotherapy could prolong the postoperative survival time in patients with early stages pancreatic ductal adenocarcinoma (PDAC). Methods:A total of 5280 stage ⅠA -ⅡB PDAC patients diagnosed from 2010 to 2015 were selected from surveillance,epidemiology,and end results (SEER) database. Propensity score matching (PSM) analysis was adopted to reduce the baseline differences between the groups. Univariate survival analysis was conducted with the Kaplan-Meier method. Multivariate survival analysis was performed with the Cox proportional hazards model. Results:Univariate and multivariate survival analyses showed that age, differentiation, stage, chemotherapy were independent risk factors for the survival of PDAC patients. After PSM, it is found that adjuvant chemotherapy could prolong the median overall survival time (mOS) for stage ⅠB, ⅡA and ⅡB patients. However, for stage ⅠA patients, there were no significant differences in 3-year survival rate and mOS between patients with chemotherapy (n=283) and without chemotherapy (n=229) (57.4% vs 55.6%, 44.0?months vs 43.0?months, all P>0.05). Further analyses show that among 101 patients with well differentiated PDAC and 294 patients with moderately differentiated PDAC, there were no significant differences in 3-year survival rate and mOS between patients with and without chemotherapy (allP>0.05). Among 117 patients with low-differentiated + undifferentiated PDAC, 3-year survival rate and mOS in patients with chemotherapy were significantly better than those without chemotherapy (48.5% vs 34.1%, 38.0?months vs 20.0?months, allP<0.05).Conclusion:Chemotherapy regimen used currently is not beneficial for patients with moderately and well differentiated stage ⅠA PDAC, but it is an independent prognostic factor for low-differentiated + undifferentiated PDAC patients.

Factors affecting the efficacy of repetitive transcranial magnetic stimulation for patients with Alzheimer’s disease
WANG Jintao,HUANG Lei,WEI Lili,CHEN Wei
J Zhejiang Univ (Med Sci), 2021, 50(3): 383-389.   https://doi.org/10.3724/zdxbyxb-2021-0184
Abstract( 24 )   HTML( 3 )     PDF(2045KB)( 14 )

Repetitive transcranial magnetic stimulation (rTMS) is a safe and non-invasive technique. In recent years, many studies have demonstrated that rTMS can improve cognitive function in Alzheimer’s disease (AD) patients and has potential as a therapeutic method for AD. However, the efficacy varies greatly with different rTMS treatment regimens, which is related to the frequency, type, location, duration, intensity and focusing power of stimulation. Recent studies have shown that high-frequency stimulation is superior to low-frequency stimulation; efficacy of intermittent theta burst stimulation (iTBS) is similar to that of conventional rTMS, but iTBS treatment session is shorter and might be more acceptable for AD patients; rTMS stimulation sites targeting AD-damaged brain regions or associated networks would be more effective; short-term intensive treatment combined with long-term maintenance treatment can gain long-term efficacy; dynamic adjustment of stimulus intensity combined with the degree of cognitive impairment can enhance the efficacy; functional connection based on functional magnetic resonance imaging may improve the focusing power of rTMS. In this article, we review the factors related to the efficacy of rTMS, to provide reference for feasible rTMS therapeutic regimens of AD.

Research advance of Nrf2 on atherosclerosis by regulating vascular smooth muscle cell
ZHUANG Wenwen,YANG Yongqi,LI Hongliang,LIANG Jingyan
J Zhejiang Univ (Med Sci), 2021, 50(3): 390-395.   https://doi.org/10.3724/zdxbyxb-2021-0190
Abstract( 14 )   HTML( 4 )     PDF(2017KB)( 16 )

Atherosclerosis is a common pathological change in cardiovascular disease. Vascular smooth muscle cell is the main source of plaque cell and extracellular matrix, and nuclear factor-erythroid 2-related factor 2 (Nrf2) is a key transcription factor regulating the function of vascular smooth muscle cell. In the process of atherosclerosis, Nrf2 signaling pathway has the following regulatory effects on vascular smooth muscle cell: regulating the phenotype of vascular smooth muscle cell to change to the direction conducive to the alleviation of disease progression; inhibiting the proliferation and migration of vascular smooth muscle cell; mitigating the level of blood lipid; alleviating vascular smooth muscle cell calcification, aging and apoptosis process. This article reviews the specific mechanisms of Nrf2 regulating atherosclerosis, such as phenotypic transformation, proliferation and migration, lipid metabolism, calcification, aging and apoptosis in atherosclerosis, in order to provide a basis for understanding the molecular mechanism of atherosclerosis development and finding therapeutic targets.

Research progress on proteasome subunits in regulating occurrence and development of hepatocellular carcinoma
HU Jingyi,WANG Qingqing,LIU Yang
J Zhejiang Univ (Med Sci), 2021, 50(3): 396-402.   https://doi.org/10.3724/zdxbyxb-2021-0146
Abstract( 20 )   HTML( 1 )     PDF(2627KB)( 10 )

Proteasome is the eukaryotic organelle responsible for degradation of short-lived proteins and involved in maintaining cellular protein homeostasis. It has been reported that during the occurrence and development of hepatocellular carcinoma (HCC), the regulatory particle subunits of proteasome regulate a series of tumor-related proteins, and proliferation, survival-associated signaling molecules, including PTEN gene, P53, Bcl-2, Bcl-2 interacting mediator of cell death (Bim), cyclin-dependent kinase 4(CDK4), transforming growth factor β receptor (TGFBR), E2F1, growth factor receptor-bound protein 2 (GRB2) . Meanwhile, these subunits regulate some tumor-associated pathway protein, such as signal transducer and activator of transcription 3 (STAT3) and protein kinase B (AKT), inducing their malfunction to promote the occurrence, proliferation, invasion and metastasis of HCC. The core particle subunits are more to perform the degradation of HCC-related proteins, so inhibitors targeting the core particle show a good anti-tumor effect. This review summarizes the current research progress on the regulation and mechanism of proteasome subunits in promoting the occurrence and development of HCC.

Progress on mitochondrial silence information regulator family in epilepsy
ZHU Feng,XIANG Yingchun,ZENG Linghui
J Zhejiang Univ (Med Sci), 2021, 50(3): 403-408.   https://doi.org/10.3724/zdxbyxb-2021-0163
Abstract( 14 )   HTML( 3 )     PDF(2036KB)( 2 )

SIRT3, SIRT4 and SIRT5 are located in mitochondria and also known as mitochondrial sirtuins. They play important roles in regulating many cellular functions including cell survival, cell cycle or apoptosis, DNA repair and metabolism. Mitochondrial sirtuins are involved in the protection of mitochondrial integrity and energy metabolism under stress regulating the expression of neurotransmitter receptors, neurotrophins, extracellular matrix proteins and various transcription factors, thus involved in epileptogenesis triggered by both genetic or acquired factors. Here we review research progress on the actions of mitochondrial sirtuin in epilepsy; and discuss the challenges and perspectives of mitochondrial sirtuin as a potential therapeutic target for epilepsy.

17 articles