Loading...

Current Issue

, Volume 46 Issue 1 Previous Issue    Next Issue
Mechanisms of histamine ameliorating memory impairment induced by pentylenetetrazole-kindling epilepsy in rats
ZHANG Lisan,CHEN Guanfeng,CHEN Jiefang,HE Xudong,HU Xingyue
J Zhejiang Univ (Med Sci), 2017, 46(1): 1-6.   https://doi.org/10.3785/j.issn.1008-9292.2017.02.01
Abstract( 620 )   HTML( 138 )     PDF(1093KB)( 521 )
Objective

To investigate the effects of neuronal histamine on spatial memory acquisition impairment in rats with pentylenetetrazole-kindling epilepsy, and to explore its mechanisms.

Methods

A subconvulsive dose of pentylenetetrazole (35 mg/kg) was intraperitoneally injected in rats every 48 h to induce chemical kindling until fully kindled. Morris water maze was used to measure the spatial memory acquisition of the rats one week after fully pentylenetetrazole-kindled, and the histamine contents in different brain areas were measured spectrofluorometrically. Different dosages of hitidine (the precursor of histamine), pyrilamine (H1 receptor antagonist), and zolantidine (H2 receptor antagonist) were intraperitoneally injected, and their effects on spatial memory acquisition of the rats were observed.

Results

Compared with control group, escape latencies were significantly prolonged on Morris water maze training day 2 and day 3 in pentylenetetrazole-kindling epilepsy rats (all P < 0.05); and the histamine contents in hippocampus, thalamus and hypothalamus were decreased significantly (all P < 0.05). Escape latencies were markedly shortened on day 3 by intraperitoneally injected with histidine 500 mg/kg, and on day 2 and day 3 by intraperitoneally injected with histidine 1000 mg/kg in pentylenetetrazole-kindling epilepsy rats (all P < 0.05). The protection of histidine was reversed by zolantidine (10 and 20 mg/kg), but not by pyrilamine.

Conclusion

Neuronal histamine can improve the spatial memory acquisition impairment in rats with pentylenetetrazole-kindling epilepsy, and the activation of H2 receptors is possibly involved in the protective effects of histamine.

Effects of crocin on hippocampus rapid kindling epilepsy in mice
WANG Xiting,TANG Oufeng,YE Yilu,ZHENG Mingzhi,HU Jue,CHEN Zhong,ZHONG Kai
J Zhejiang Univ (Med Sci), 2017, 46(1): 7-14.   https://doi.org/10.3785/j.issn.1008-9292.2017.02.02
Abstract( 896 )   HTML( 48 )     PDF(1151KB)( 599 )
Objective

To investigate the effect of crocin on the progression and generalized seizure of temporal lobe epilepsy in mice.

Methods

Hippocampus rapid kindling model was established in C57BL/6J mice. The effects of crocin on seizure stage, afterdischarge duration (ADD), number of stimulation in each stage and final state, the incidence of generalized seizure (GS), average seizure stage and ADD were observed.

Results

Crocin (20 mg/kg) significantly retarded behavioral seizure stages (P < 0.05) and shortened cumulative ADD (P < 0.01) during hippocampus rapid kindling acquisition in mice compared with vehicle group. Meanwhile, number of stimulations in stage 1-2 was significantly increased (P < 0.05) and the incidence of fully kindled animals was significantly decreased (P < 0.01). However, 10 or 50 mg/kg crocin showed no significant effect on the above indexes (all P>0.05). Crocin (100 or 200 mg/kg) significantly decreased the incidence of GS (all P < 0.01) and reduced average seizure stages (all P < 0.01) in fully-kindled mice compared with vehicle group; Fifty mg/kg crocin only reduced average seizure stages (P < 0.05).

Conclusion

Low-dose crocin can retard the progression in hippocampus rapid kindling acquisition in mice, while high-dose crocin relieves the GS in fully-kindled mice, which suggests that crocin may be a potential anti-epileptic compound.

The role of central cholinergic system in epilepsy
WANG Ying,WANG Yi,CHEN Zhong
J Zhejiang Univ (Med Sci), 2017, 46(1): 15-21.   https://doi.org/10.3785/j.issn.1008-9292.2017.02.03
Abstract( 996 )   HTML( 27 )     PDF(1058KB)( 719 )

Epilepsy is a chronic neurological disorder, which is not only related to the imbalance between excitatory glutamic neurons and inhibitory GABAergic neurons, but also related to abnormal central cholinergic regulation. This article summarizes the scientific background and experimental data about cholinergic dysfunction in epilepsy from both cellular and network levels, further discusses the exact role of cholinergic system in epilepsy. In the cellular level, several types of epilepsy are believed to be associated with aberrant metabotropic muscarinic receptors in several different brain areas, while the mutations of ionotropic nicotinic receptors have been reported to result in a specific type of epilepsy-autosomal dominant nocturnal frontal lobe epilepsy. In the network level, cholinergic projection neurons as well as their interaction with other neurons may regulate the development of epilepsy, especially the cholinergic circuit from basal forebrain to hippocampus, while cholinergic local interneurons have not been reported to be associated with epilepsy. With the development of optogenetics and other techniques, dissect and regulate cholinergic related epilepsy circuit has become a hotspot of epilepsy research.

Temporal lobe epilepsy and adult hippocampal neurogenesis
CHEN Liying,WANG Yi,CHEN Zhong
J Zhejiang Univ (Med Sci), 2017, 46(1): 22-29.   https://doi.org/10.3785/j.issn.1008-9292.2017.02.04
Abstract( 730 )   HTML( 14 )     PDF(1038KB)( 449 )

Temporal lobe epilepsy (TLE) is a common and severe neurological disorder which is often intractable. It can not only damage the normal structure and function of hippocampus, but also affect the neurogenesis in dentate gyrus (DG). It is well documented from researches on the animal models of TLE that after a latent period of several days, prolonged seizure activity leads to a dramatic increase in mitotic activity in the hippocampal DG. However, cell proliferation returns to baseline levels within 3-4 weeks after status epilepticus (SE). Meanwhile, there are two major abnormalities of DG neurogenesis, including the formation of hilar basal dendrites and the ectopic migration of newborn granule cells into the polymorphic cell layer, which may affect epileptogenesis and seizure onset. However, the specific contribution of these abnormalities to seizures is still unknown. In other words, whether they are anti-epileptic or pro-epileptic is still under heated discussion. This article systematically reviews current knowledge on neurogenesis and epilepsy based on the results of studies in recent years and discusses the possible roles of neurogenesis in epileptogenesis and pathologic mechanisms, so as to provide information for the potential application of neurogenesis as a new clinical therapeutic target for temporal lobe epilepsy.

Monitoring time of interictal epileptiform discharges by long-term video EEG in patients with epilepsy
WU Han,WANG Zhongjin,MING Wenjie,WANG Shuang,DING Meiping
J Zhejiang Univ (Med Sci), 2017, 46(1): 30-35.   https://doi.org/10.3785/j.issn.1008-9292.2017.02.05
Abstract( 1102 )   HTML( 8 )     PDF(1067KB)( 428 )
Objective

To optimize the monitoring time of interictal epileptiform discharges (IED) in patients with epilepsy by long-term video electroencephalogram (VEEG).

Methods

The cumulative percentages of IED detected by VEEG in 346 epilepsy patients (349 times) with different purposes, different waking sleep states and different MRI findings were retrospectively analyzed. According to the purposes, there were 164 patients (165 times) for clarifying diagnosis, 124 patients (124 times) for preoperative evaluation and 58 patients (60 times) for adjustment of medications. According to MRI results, there were responsible lesions in 98 patients (98 times) and no responsible lesions in 173 patients (174 times).

Results

Among 346 patients (349 times), IED was detected within 24 h in 231 patients (times). The percentage of detection in patients with purpose of preoperative evaluation was higher than those with purpose of diagnosis and medication adjustment. The detection of LED was gradually increased in first 8 h with 59.0%, then stably in 24 h. 46.8% IED was recorded during sleep time, particularly in the second stage of sleep. The cumulative percentage of IED in patients with abnormal MRI findings was higher in all periods. It reached 83.7% within 8 h, and then tended to be stable.

Conclusion

The study shows that LED should be monitored by VEEG at least 8 hours and should include the second stage of sleep in patients with epilepsy. Patients with refractory epilepsy and with abnormal lesions on MRI should record IED more frequently.

Hypoxia-inducible factor-1α and CD133 predicts pathological complete response and survival for locally advanced rectal cancer patients after neoadjuvant chemoradiotherapy
CAI Cheng,WANG Jianping,ZHONG Zhifeng,DAI Zhihui,WANG Qinghua,DONG Wuzhen,SHI Hongqi,LIU Qingwei,DU Jinlin
J Zhejiang Univ (Med Sci), 2017, 46(1): 36-43.   https://doi.org/10.3785/j.issn.1008-9292.2017.02.06
Abstract( 723 )   HTML( 32 )     PDF(1143KB)( 336 )
Objective

To investigate the expression of hypoxia-inducible factor 1α (HIF-1α) and CD133 in predicting pathologic remission and survival of patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy.

Methods

One hundred and fourteen patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy from January 2010 to December 2015 in Jinhua Municipal Central Hospital were enrolled in the study. RT-PCR and immunohistochemistry methods were used to detect the mRNA and protein expression of HIF-1α and CD133 before and after chemoradiotherapy. Spearman rank correlation was used to analyze the correlation between HIF-1α and CD133 mRNA expression. Univariate and logistic multivariate analyses were used to determine the factors related to pathological complete response (pCR). Logistic regression analysis and Cox's proportional hazard model were used to determine factors related to overall survival and recurrence-free survival.

Results

The expression of HIF-1α and CD133 mRNA was correlated with pT, ypTNM, pCR, recurrence and metastasis of rectal cancer, while not correlated with sex, age and BMI of patients. HIF-1α mRNA expression was positively correlated with CD133 mRNA expression (α=0.579, P=0.000). Immunohistochemistry analysis showed that residual cancer cells strongly expressing HIF-1α also expressed CD133 strongly. Univariate analysis showed that HIF-1α mRNA and CD133 mRNA were significantly correlated with pCR (P=0.001, P=0.022, respectively). Multivariate analysis showed that HIF-1α and CD133 mRNA expression were independent prognostic factors of pCR (P=0.012, P=0.047, respectively). Cox regression analysis showed that the expression of HIF-1α mRNA and CD133 mRNA were independent predictors of recurrence-free survival and overall survival (P=0.025, P=0.033, respectively).

Conclusion

The study indicates that HIF-1α and CD133 can predict pathological complete remission and survival of patients with locally advanced rectal cancer.

Clinical investigation on transarterial chemoembolization with indigenous drug-eluting beads in treatment of unresectable hepatocellular carcinoma
CHEN Gang,ZHANG Ding,YING Yacao,WANG Zhifeng,TAO Wei,ZHU Hao,ZHANG Jingfeng,PENG Zhiyi
J Zhejiang Univ (Med Sci), 2017, 46(1): 44-51.   https://doi.org/10.3785/j.issn.1008-9292.2017.02.07
Abstract( 1253 )   HTML( 7 )     PDF(1197KB)( 483 )
Objective

To evaluate the efficacy and safety of drug-eluding beads transarterial chemoembolization (DEB-TACE) in treatment of unrecectable hepatocellular carcinoma (HCC).

Methods

The clinical data of 42 consecutive HCC patients undergoing TACE were retrospectively analyzed, including 20 cases received conventional TACE (cTACE group) and 22 cases received TACE with epirubicine-loaded microspheres (CalliSpheres?) (DEB-TACE group). MRI scans were performed 1 week before and 1, 3 and 6 months after initial therapy. The response to treatment, disease recurrence, complications and adverse effects were documented and compared between two groups.

Results

There were no significant differences in 1-month, 3-month and 6-month objective response rate (CR+PR) and disease control rate (CR+PR+SD), disease recurrence, complications and adverse effects of interventional therapy between cTACE group and DEB-TACE group. Additionally, there were no significant differences about locoregional biliary injuries, intrahepatic biloma, and newly detected intra-or extrahepatic HCC on MRI between cTACE group and DEB-TACE group.

Conclusion

There were no statistically significant differences between cTACE group and DEB-TACE group with regard to the short-term response, disease recurrence, complications and side effects. Hepatic-locoregional complications may be more frequent in DEB-TACE group than those in cTACE group.

Video head impulse test for evaluation of vestibular function in patients with vestibular neuritis and benign paroxysmal positional vertigo
GUAN Qiongfeng,ZHANG Lisan,HONG Wenke,YANG Yi,CHEN Zhaoying,ZHANG Dan,HU Xingyue
J Zhejiang Univ (Med Sci), 2017, 46(1): 52-58.   https://doi.org/10.3785/j.issn.1008-9292.2017.02.08
Abstract( 1875 )   HTML( 16 )     PDF(1199KB)( 510 )
Objective

To assess the clinical application of video head impulse test (vHIT) for vestibular function in vestibular neuritis (VN) and benign paroxysmal positional vertigo (BPPV) patients.

Methods

Thirty-three patients with VN and 43 patients with BPPV were enrolled from Sir Run Run Shaw Hospital and Ningbo Second Hospital from March 15 to September 10, 2015; and 50 healthy controls were also enrolled in the study. vHIT was used to quantitatively test the vestibulo-ocular reflex (VOR) gains of a pair of horizontal semicircular canals. VOR gains two pairs of vertical semicircular canals, and the corresponding asymmetrical value of three VOR gains. The saccades information was also recorded.

Results

Compared with the healthy control group and BPPV patients, the affected horizontal and vertical VOR gains were declined and the corresponding asymmetries were increased in VN patients (all P < 0.01). BPPV group also showed higher vertical VOR gain asymmetries compared with the healthy control group (all P < 0.01), but no significant difference was observed in VOR gains and horizontal VOR gain asymmetry (all P>0.05). The sensibility of vHIT in diagnosis of VN was 87.9%. Among 33 VN patients, 22 were diagnosed with superior vestibular nerve dysfunction, 7 were found with inferior vestibular nerve dysfunction and 3 were with both dysfunction; and 1 case was not distinguished.

Conclusion

Video head impulse test can quantitatively evaluate the vestibular dysfunction of VN and can help early diagnosis of VN, which may be widely used in clinic.

Localization of gestational age reference table and its application in prenatal screening
DOU Linlin,YANG Guohui,MO Weiming
J Zhejiang Univ (Med Sci), 2017, 46(1): 59-65.   https://doi.org/10.3785/j.issn.1008-9292.2017.02.09
Abstract( 588 )   HTML( 4 )     PDF(1075KB)( 388 )
Objective

To establish a fetal biparietal diameter (BPD)-gestational age formula based on the data of pregnant women from Xiaoshan District of Hangzhou, and to evaluate its application in prenatal screening.

Methods

Data of 3500 pregnant women with gestational age between 15 weeks and 19 weeks+6 receiving prenatal screening in Xiaoshan Hospital during May 2014 and May 2015 were collected. BPDs were used to establish a localized BPD-gestational age formula. The localized formula was used to evaluate the prenatal screening risks in 1759 pregnant women with irregular menstrual cycles or uncertain last menstrual period (LMP) in Xiaoshan District, and the results were compared with those calculated using formula in LifeCycle 4.0.

Results

With localized formula, the total positive rate of Down syndrome, trisomy 18 syndrome and deformity of neural tube was decreased from 6.96% to 5.85% (P < 0.05), in which the positive rate of Down syndrome decreased (P < 0.05), that of deformity of neural tube increased (P < 0.05), and that of trisomy 18 syndrome remained the same (P>0.05). The median MoMs of free-hCG β and α-fetoprotein calculated using localized formula were significantly different from those calculated using the formula in LifeCycle 4.0 (all P < 0.05), and the former ones were more closer to 1. For women of fetus diagnosed with the above diseases, the positive rate calculated using localized formula was almost the same as that calculated using the formula in LifeCycle 4.0.

Conclusion

BPD-gestational age formula should be localized based on the statistical analysis of the local population, which will help to reduce the false positive rate, and make the results more accurate and reliable in prenatal screening.

LC/MS guided approach to discovering nephroprotective substances from Huangkui capsule
MA Tingting,WANG Yi,CHEN Xiaoqian,ZHAO Xiaoping
J Zhejiang Univ (Med Sci), 2017, 46(1): 66-73.   https://doi.org/10.3785/j.issn.1008-9292.2017.02.10
Abstract( 848 )   HTML( 5 )     PDF(1292KB)( 385 )
Objective

To discover the nephroprotective substances from Huangkui capsule.

Methods

The components of Huangkui capsule were isolated by preparative liquid chromatography, and the active components were screened by LC/MS and identified. The adriamycine-injured HK-2 cells were treated with various active components with different concentrations, and the malonaldehyde (MDA) content, adenosine triphosphate (ATP) level and mitochondrial oxygen consumption rate were measured to verify the protective activity of the compounds.

Results

Four active components in Huangkui capsule were identified to exert nephroprotective effects. Fifteen flavanoids from these four components were tentatively identified by LC/MS, and hyperin, myricetin, quercetin, rutin and isoquercetin were confirmed. Hyperin, myricetin quercetin and rutin showed dose-dependent protective effects on injured HK-2 cells. Espacially, hyperin significantly reduced MDA content, quercetin and rutin significantly increased ATP level, and myricetin significantly increased mitochondrial oxygen consumption rate.

Conclusion

Hyperin, myricetin, querctein and rutin might be the potential nephroprotective compounds in Huangkui capsule, their effects may be related to the inhibition of lipid peroxidation and the alleviation of mitochondrial damage.

Antiendotoxin effect of Jinhuaqingre capsules
HOU Jiafu,WU Leilei,CAI Yuting,GAO Changjiu,AN Jindan,YU Zhongcheng
J Zhejiang Univ (Med Sci), 2017, 46(1): 74-79.   https://doi.org/10.3785/j.issn.1008-9292.2017.02.11
Abstract( 631 )   HTML( 2 )     PDF(1038KB)( 290 )
Objective

To investigate the anti-pyretic and anti-endotoxin effect of Chinese herb medicine Jinhuaqingre capsules.

Methods

Thirty healthy male New Zealand rabbits with lipopolysaccharide-induced fever were divided into 5 groups (6 rabbits in each): animals in model group were given normal saline by gavage, animals in positive control group were given aspirin (0.2 g/kg), and animals in Jinhuaqingre groups were given Jinhuaqingre capsules 6.0, 3.0 or 1.5 g/kg, respectively. The changes in body temperature of rabbits were observed. Fifty healthy Kunming mice were divided into 5 groups (10 mice in each): mice in model group were given normal saline by gavage, mice in positive control group were given aspirin (0.2 g/kg), and those in Jinhuaqingre groups were given Jinhuaqingre capsules 6.0, 3.0, 1.5 g/kg, respectively. Matrix coloration method was used to detect the degradation rate of endotoxin in mice.

Results

The body temperature in rabbits of high and medium dose Jinhuaqingre capsule groups declined significantly 60 min after drug administration, and the temperature of high-dose group returned to the baseline after 300 min; while the body temperature of low-dose group started to decline at 180 min after drug administration. The endotoxin degradation rates in mice of high, medium and low dose groups was (56.73±3.12)%, (47.23±1.77)% and (21.08±2.30)% at 30 min after drug administration; those were (82.76±1.00)%, (64.75±1.77)% and (38.21±1.57)% at 60 min after drug administration, respectively.

Conclusion

Chinese herb medicine Jinhuanigre capsules have anti-pyretic and anti-endotoxin effects, which may provide a new option for the treatment of heat-toxin syndrome.

Application progress on near infrared spectroscopy in quality control and process monitoring of traditional Chinese medicine
LI Wenlong,QU Haibin
J Zhejiang Univ (Med Sci), 2017, 46(1): 80-88.   https://doi.org/10.3785/j.issn.1008-9292.2017.02.12
Abstract( 608 )   HTML( 4 )     PDF(1012KB)( 543 )

The industry of traditional Chinese medicine (TCM) encounters problems like quality fluctuation of raw materials and unstandardized production process. Near infrared (NIR) spectroscopy technology is widely used in quality control of TCM because of its abundant information, fast and nondestructive characters. The main applications include quantitative analysis of Chinese medicinal materials, intermediates and Chinese patent medicines; the authenticity of TCM, species, origins and manufacturers; monitoring and control of the extraction, alcohol precipitation, column chromatography and blending process. This article reviews the progress on the application of NIR spectroscopy technology in TCM field. In view of the problems existing in the application, the article proposes that the standardization of NIR analysis method should be developed according to specific characteristics of TCM, which will promote the application of NIR technology in the TCM industry.

Iodine 131 joint radio frequency ablation treatment for child with hyperthyroidism goiter: one case report
CHEN Yonghua,LIANG Li,FANG Yanlan,WANG Chunlin,LI Linfa,JIANG Tian'an
J Zhejiang Univ (Med Sci), 2017, 46(1): 89-91.   https://doi.org/10.3785/j.issn.1008-9292.2017.02.13
Abstract( 523 )   HTML( 3 )     PDF(965KB)( 303 )

A 12-year-old girl presented with a history of cervical mass, and one week of throat discomfort and dyspnea. Five years ago, the patient was diagnosed as Hashimoto's thyroiditis and hyperthyroidism; she received antithyroid drug treatment, but the result was not satisfactory. B-ultrasonic showed that the size of thyroid gland was 8.1 cm×3.2 cm in the left and 8.2 cm×4.8 cm in the right. After iodine 131 combined with radiofrequency ablation (RFA) treatment, throat discomfort and recumbent breathing difficulties disappeared, and B-ultrasonic showed that the size of thyroid reduced to 2.3 cm×1.7 cm (left) and 2.8 cm×2.0 cm (right). No recurrence was observed during the two and a half years of follow-up.

Research progress on mechanism of Nix-mediated mitophagy
ZHENG Yanrong,ZHANG Xiangnan,CHEN Zhong
J Zhejiang Univ (Med Sci), 2017, 46(1): 92-96.   https://doi.org/10.3785/j.issn.1008-9292.2017.02.14
Abstract( 1309 )   HTML( 8 )     PDF(1026KB)( 535 )

Autophagy is fundamental to maintain cellular homeostasis. As one kind of the most well-studied selective autophagy, autophagy of mitochondria (mitophagy) is crucial for the clearance of damaged mitochondria. Mitophagy dysfunction has been proved to be closely associated with many human diseases. Nix is a key protein for mitophagy during the maturation of reticulocytes. However, the detailed molecular mechanisms underlying Nix-mediated mitophagy are not fully understood. This article summarizes three possible working models of Nix in mitophagy induction. Firstly, Nix can interplay with Parkin, another important protein for mitophagy, to initiate mitophagy. Secondly, Nix can serve as a receptor for autophagy machinery by interacting with Atg8 family through its LIR motif. Finally, as a BH3-only protein, Nix can compete with Beclin-1 to bind other members of Bcl-2 family resulting in increased free Beclin-1 in cytosol, which further promotes autophagy flux.

Research progress on the animal models and treatment strategies of diabetic foot ulcer
GAO Siqian,SHEN Yongmei,GENG Funeng,LI Yanhua,GAO Jianqing
J Zhejiang Univ (Med Sci), 2017, 46(1): 97-105.   https://doi.org/10.3785/j.issn.1008-9292.2017.02.15
Abstract( 747 )   HTML( 8 )     PDF(1012KB)( 437 )

The suitable experimental animal model is important in research of pathogenesis and therapeutic strategies of diabetic foot ulcer, and the murine model is the most commonly used one at present. It can be divided into two types: the animal model simulating pathological conditions and the model simulating clinical symptoms. This article reviews the current research progress on the mechanisms of diabetic ulcer pathogenesis, and relevant treatment strategies, including the inhibition of matrix metalloproteinases (MMPs) expression, promotion of angiogenesis and anti-inflammatory therapy.

Focus on the 14th International Symposium on Dendritic Cells
LU Shen,WANG Qingqing
J Zhejiang Univ (Med Sci), 2017, 46(1): 106-109.   https://doi.org/10.3785/j.issn.1008-9292.2017.02.16
Abstract( 544 )   HTML( 10 )     PDF(970KB)( 337 )
16 articles