The morbidities of nervous system diseases,such as cerebrovascular disease and Alzheimer's disease,are increasing with the aging of population.As a theory and methodology,system theory plays an important role in the studies of nervous system diseases.Using the principle of system theory,this paper discusses the research methodology of nervous system diseases based on the latest advances in aetiology,diagnosis and treatment of some nervous system diseases from the integration,hiberarchy and scheduling aspects of a system.

Objective To evaluate the efficacy and safety of peroral endoscopic myotomy (POEM) for achalasia.Methods A total of 40 achalasia patients who underwent POEM at our hospital were enrolled.The outcomes of Eckardt score,Barium contrast imaging,esophageal manometry as well as esophagogastroscopy were assessed before and at 6th day,1 month,3 months and 6 months after POEM respectively.Results All 40 patients successfully underwent POEM,with the mean operation time 57.2 ± 18.4 minutes.lntraoperative mediastinal and subcutaneous emphysema occurred on two patients.All patients had significant symptom relief after POEM (Eckardt score ≤ 3).The patients had a mean follow-up of 13.3 months.Two patients had symptom relapse,and treatment success rate (Eckardt score ≤3) was 90％ in 6-month follow up.According to high-resolution manometry (HRM),the resting lower esophageal sphincter (LES) pressures were 30.6 and 15.8 mmHg (P =0.001),and intergrated relaxation pressure(IRPs) were 28.1 and 12.2 mmHg (P =0.000) before and after POEM,respectively.The diameter of the esophageal lumen was 4.2 cm and 3.1 cm before and after POEM (P＜0.001).Conclusion POEM is safe and effective in a short term with less complications.Further follow-up studies are needed to evaluate long-term outcomes.

Objective To observe the effect of low level infrasound on neuropathic pain and explore its underlying mechanism. Methods Rats were divided into experimental and control groups after their L5 spinal nerves had been ligated to create a neuropathic pain model. The experimental group was subjected to 40 to 80 dB infra sound. The control group received no infrasound treatment. Paw withdrawal latency in response to heat radiation was measured and the average gray scale of the microglia in a slice of the L5 spinal cord was compared. Results The experimental group expressed significantly lengthened paw withdrawal latency on the 12th and 14th day. The average gray scale showed significantly weakened activation of spinal microglia in the 2nd week of infrasound treatment compared with the control group. Conclusion Low level infrasound can ameliorate neuropathic pain to a certain extent,which might be related with inhibition of spinal microglia.

Objective To observe the preliminary application of intraoperative optical coherence tomography (iOCT) in vitreous retinal surgery and the influencing factors of the imaging quality.Methods A retrospective case study.A total of 132 subjects were chosen in June 2015 and April 2016 in our hospital.All the subjects were taken vitreous retinal surgery and iOCT scanning.The patients included 46 males and 86 females,with an average age of 61.7 years.111 cases had macular diseases and 21 cases had vitreous hemorrhage.Cases are divided into high myopia and non high myopia group according to ocular axial length (AL),28 eyes in high myopia group (AL≥26 mm),104 eyes in non-high myopia (AL＜26 mm).The scanning time,image quality and eye conditions were observed during the operation.The discordance between surgeon microscope visualization of the pathology and the findings of the iOCT and the postoperative adverse reactions were also observed.Results The iOCT images were identified in 124 of 132 subjects,while were not identified in 8 eyes.For the macular area morphology change,iOCT tips and surgeon judgment rate was inconsistent in 22 eyes (16.7％).For the operation guidance value,change the operation rate of 12/132,accounted for 9.1％.The iOCT imaging quality of high myopia groups was lower than the non-high myopia groups (x2-17.13,P=0.001).Corneal edema and operation time were considered as influencing factors on the quality of the imaging in the non-high myopia groups (r =3.75,6.18;P 0.049,0.013).There were no complications such as endophthalmitis.Conclusions The surgeon can observe morphological changes in the macular area through iOCT which is difficult to be observed by operating microscope and selected reasonable operation method during the surgery.High myopia,corneal edema and operation time affect the image quality.

Objective To investigate the effects of intravitreous injection of conbercept for macular edema secondary to retinalvein occlusion(RVO) during 6 months period.Methods A retrospective clinical study.34 patients (34 eyes) were included in this study,who were diagnosed with macular edema due to retinal vein occlusion by ophthalmologic examination,fundus photography,optical coherence tomography (OCT),fundus fluorescein angiography and other methods.The best corrected visual acuity (BCVA) was examined using the international standard visual acuity chart,and the results were converted to the logMAR visual acuity.The average logMAR BCVA was 0.90 ± 0.68,and the mean macular central retinal thickness (CMT) was (672.27±227.51) μm before treatment.All subjects received intravitreal injection of 0.5 mg conbercept (0.05 ml) at the first visit.Injections were repeated based on the visual acuity changes and the OCT findings.34 eyes received 69 times of injection,the average number of injections was 2.03 ± 1.03.BCVA,OCT were examined before and after treatment using the same method.BCVA and CMT changes,drugs and treatments associated cardiac and cerebral vascular accident,intraocular pressure elevation,retinal tears,retinal detachment,endophthalmitis and other complications after treatment were observed.Linear correlation analysis was used to analyze the correlation between prognosis BCVA and baseline BCVA,correlation between prognosis BCVA and baseline CMT,and also correlation between BCVA and CMT at different time points before and after treatment.Results At 1 week and 1,2,3,6 months after treatment,the average logMAR BCVA was 0.65±0.61,0.56±0.61,0.46±0.55,0.56±0.71,0.44±0.48 respectively.During 1,2,3,6 months after treatment,the mean logMAR BCVA were improved with statistically significant difference (Z=34.029,47.294,41.338,43.603;P＜0.05),while 1 week after treatment showed no obvious improvement (Z=21.941,P＞0.05).At 1 week and 1,2,3,6 months after treatment,the average CMT was (285.89 ± 96.69),(256.65 ± 143.39),(278.68 ± 156.92),(290.11 ± 188.17),(217.15 ± 48.04) μm respectively.At 1 week and 1,2,3,6 months after treatment,the mean CMT were all decreased with statistically significant difference (Z=68.500,98.735,93.235,91.132,109.162;P＜0.05).There was a positive correlation between the prognosis visual acuity and preoperative visual acuity (r=0.682,P＜0.05).However,there was no correlation between the prognosis vision and the degree of macular edema before treatment (r=0.078,P＞0.05).Before and 3,6 months after treatment,BCVA was negatively correlated with CMT (r=0.491,0.416,0.386;P＜0.05),while there was no correlation in other time points (r =0.145,0.217,0.177;P＞ 0.05).Systemic adverse reactions and persistent intraocular pressure elevation,iatrogenic cataract,retinal detachment,retinal tear,endophthalmitis and ocular complications were never found in the follow-up period.Conclusion Intravitreal conbercept is a safe and effective approach for RVO,which can significantly improve visual acuity and reduce CMT.

Objective To design and synthesize a novel paclitaxel loaded nanoparticle with reactive oxygen species (ROS) response, and characterize its structure, and investigate its stability, in vitro drug responsive release, cellular uptake and in vitro antitumor activity. Methods The PEG-2S-PTX monomer was synthesized by coupling the hydrophilic polyethylene glycol (PEG) with hydrophobic paclitaxel (PTX) via a thioether chain (2S), and the prodrug nanoparticles (PEG-2S-PTX NPs) were prepared by self-assembly. Meanwhile, using succinic anhydride (SA) as the linking group to synthesize the PEG-SA-PTX monomer and prepare the other prodrug nanoparticles (PEG-SA-PTX NPs) as control. The structures of PEG-2S-PTX and PEG-SA-PTX monomer were confirmed by 1H-NMR. The diameter and stability of the nanoparticles were detected by dynamic light scattering (DLS). The PTX release kinetics under oxidizing condition was detected by high performance liquid chromatography (HPLC) method. And the cellular uptake efficiency of nanoparticles by MCF-7 cells was observed by fluorescence microscope. The in vitro antitumor effects of nanoparticles were compared by MTT assay. Results PEG-2S-PTX and PEG-SA-PTX could both be self-assemble into nanoparticles with the diameter of (92.15±12.42) nm and (113.20±12.16) nm. PEG-2S-PTX NPs could rapidly release PTX under oxidative condition while PEG-SA-PTX NPs only showed weak responsiveness. PEG-2S-PTX NPs could be more rapidly taken up by MCF-7 cells compared with PEG-SA-PTX NPs. They both showed concentration dependent anti-tumor effects, but the cytotoxicity of PEG-2S-PTX NPs was stronger than that of PEG-SA-PTX NPs in the concentrations of 0.05, 0.1, 5, 10, 50 and 100 mg/L (P<0.05). Conclusion As paclitaxel prodrug nanoparticles with ROS responsive ability, PEG-2S-PTX NPs can rapidly release PTX in response to ROS in tumor cells, and exhibit great anti-tumor activity in vitro.

Background Major depressive disorder and insomnia often coexist,and the two may share a mechanism of pathogenesis and be affected by common underlying genes with strong pleiotropic effects.Previous genome-wide association studies(GWAS)mainly focused on single-gene morphological characters analysis,which impose limitations on showing possible pleiotropic effects.Objective To identify genetic loci related to insomnia and major depressive disorder,and to examine whether there are common genetic factors underlying both insomnia and depression.Methods The GWAS data for major depressive disorder originates from the Psychiatric Genomics Consortium(PGC),which comprises a total of 246363 depressive cases and 561190 controls.The insomnia GWAS data was downloaded from Sleep Disorder Knowledge Portal,involving 1331010 participants.Then the conditional false discovery rate(cFDR)and conjunction cFDR(ccFDR)were utilized to identify the genetic loci associated with major depressive disorder and insomnia,and pathway enrichment analysis was performed to examine the biological functions of these loci.Results A significant pleiotropic effect was detected between major depressive disorder and insomnia.By leveraging pleiotropic enrichment,21 susceptibility loci(17 novel loci)for major depressive disorder and 38 susceptibility loci(28 novel loci)for insomnia were identified with the threshold of cFDR<0.01.A total of 16 pleiotropic loci(15 novel loci)related to both major depressive disorder and insomnia were identified with the threshold of ccFDR<0.05.pathway enrichment analysis indicated that the susceptibility loci were mainly enriched in synaptic transmission pathway,such as postsynaptic density(GO:0014069,P=4.91E-04,FDR=4.84E-03),asymmetric synapse(GO:0032279,P=5.09E-04,FDR=4.84E-03),and regulation of postsynaptic membrane neurotransmitter receptor levels(GO:0099072,P=5.11E-04,FDR=1.69E-02).Conclusion A significant pleiotropic enrichment is found between major depressive disorder and insomnia,and the comorbidity mechanism is related to synaptic transmission.

Objective The invasion and metastasis of colon cancer often leads to treatment failure and mortality in patients . Our research is to investigate the influence of FoxM 1 to malignant human colon cancer line . Methods In two human colon cancer lines, the protein and mRNA expression levels of FoxM 1 were analyzed with the application of RT-PCR and Western blot , from which high-expressed HT-29 and low-expressed HCT-116 were determined.The expression of FoxM1 was down-regulated by RNA interfering in HT-29 and up-regulated by constructing overexpression transgenic line in HCT-116.The proliferation of the above cells was assayed by healing method;while the metastasis and invasion ability were examined by Transwell chamber assay . Results Two colon cancer lines were selected with high-expression or low-expression of FoxM1 separately named HT-29 and HCT-116.Application of PEX-2-FoxM1 raised after HCT-116 cells express FoxM1, cell scratches in HCT-116 experimetal group ([70.92 ±1.48]%) compared with HCT-116 control group([16.92 ±4.05]%)and HCT-116 blank control group([16.66 ±2.63]%) will markedly enhance its capabil-ity of healing (P<0.05), Transwell Chambers in membrane cells in HCT-116 experimetal group (186.0 ±6.8) compared with HCT-116 control group(42.0 ±2.0) and HCT-116 blank control grou (37.0 ± 2.2)was increased (P<0.05).On the other hand, the applied pG-PH-shFoxM1 can reduce FoxM1 expression in HT-29 cell, cell scrat-ches healing ability in HT-29 experimetal group ( [ 10 .37 ± 3.86]%) compared with HT-29 control group([34.63 ±2.35]%)and HT-29 blank control group([67.36 ±2.61]%) decreased significantly (P<0.05), Transwell Chambers in membrane cells in HT-29 experimetal group (53.0 ±1.8)compared with HT-29 control group(95.0 ±2.2)and HT-29 blank control grou(118.0 ±4.0) was also reduced (P<0.05). Conclusion The expression of FoxM1 is in close relation to the invasion and metastasis of CRC .The fact that the siRNA interfering FoxM1 could effectively inhibit the proliferation, metastasis and invasion, suggesting FoxM1 could po-tentially be a new molecular target for inhibiting the proliferation of human colon cancer line .

Objective To investigate the role of epigallocatechin gallate ( EGCG) in reversing the CpG island methylation of Rad23b and Ddit3 gene promoter and its mRNA expression induced by 0?5 Gy X-rays. Methods Thirty BALB/c male mice were randomly divided into 6 groups: control group, irradiation group, low/high dose of EGCG group, low/high dose of EGCG with irradiation group. For the irradiation group, mice were fractionally exposed with 6 MV X-rays for 10 d (0?05 Gy/d × 10 d). 2 hours after the final irradiation, all mice were killed and such tissues as blood, kidney, liver, spleen, brain, and lung were collected. Methylation and expression levels of Rad23b and Ddit3 were measured by bisulfate sequencing primers ( BSP) and Real-time PCR, respectively. Results Compare to the control group, Rad23b was hypermethylated in PBMC, liver, spleen, brain and lung (t= -20?19, -14?80, -12?05,-28?42, -12?58, P<0?05) in the irradiation group. Meanwhile, its mRNA expression level was down-regulated in PBMC, liver, brain and lung (t=25?25, 17?43, 11?53, 22?85, P<0?05). Similarly, a significant hypermethylation change of Ddit3 was observed in PBMC, liver and lung after irradiation ( t=-52?89, -20?31, -3?85, P<0?05) so that the mRNA expression of Ddit3 decreased in PBMC and liver ( t = 11?89, 16?52, P < 0?05 ). Compared to the irradiation group, EGCG with different concentrations of 10, 20 mg/kg significantly reduced the methylation level of Rad23b and Ddit3 ( t =-13?39-7?99, P<0?05), and induced re-expression of mRNA (t= -34?02 - -2?89, P<0?05). This change was more notable in the irradiation group with the high dose of EGCG. Conclusions As a natural drug, EGCG may play an important role in affecting DNA methylation and hence protects DNA from radiation damage.

Background The introvitreal injection of triamcinolone acetonide (TA) before vitrectomy for retinal with choroidal detachment (RD/CD) can alleviate inflammatory response,but it easily lead to complications under the low intraocular pressure.The study on the efficiency and safety of subtenon injection of TA for treatment of RD/CD is lack.Objective This study was to evaluate the efficiency and safety of subtenant injection of TA with vitrectomy for treatment of RD/CD.Methods A retrospective study was adopted.The data of 22 eyes of 22patients who received subtenon injection of TA with vitrectomy for RD/CD were collected and analyzed in Affiliated Eye Hospital of Wenzhou Medical University from May 2010 to June 2014.TA of 40 mg in 0.4 ml was administered subtenantly 5 days before RD repair surgery.After initiating the treatment,the therapeutic effects on uvitis were analyzed.Intraocular pressure was monitored and CD height and range were determined by B type ultrasonography before injection and 5 days after injection respectively.In addition,blood glucose and blood pressure of the patients were evaluated.Results Ocular inflammation alleviated to some degree after TA injection in all 22 eyes.The mean intraocular pressure was (5.4±2.9) mmHg (1 mmHg =0.133 kPa) in pre-injection and (8.2±4.3) mmHg in postinjection,showing a significant difference between them (t =3.430,P ＜ 0.01).The mean maximum CD height was 5.2 (3.1,6.6)mm in pre-injection and 0.9 (0,3.8)mm in post-injection,with a significant difference between the before and after injection (Z=-4.198,P＜0.01).The mean CD range was 12 (10,12) clock before injection and 3(0,6) clock after injection,and no significant difference was found between before and after injection (all at P＞0.05) (Z=-4.124,P＜0.01).There were no statistically significant difference in the changes of blood glucose and blood pressure between before and after injection.The LogMAR visual acuities were 2.14±0.46,1.29±0.57 and 1.17±0.55 before injection and 1 month,3 months after injection,respectively,with a siginificant difference among them (F =22.060,P＜0.001).The retinal reattachment rate was 95.5 ％.Conclusions Subtenon injection of TA seems to be a good option for perisurgical management of RD/CD patients,which can alleviate uvitis,increase intraocular pressure,reduce CD height and CD range.