Remote programming for subthalamic deep brain stimulation in Parkinson's disease.

Introduction: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is effective for the treatment of Parkinson's disease (PD). Moreover, remote programming is widely used in Mainland China. This necessitates evaluating the ability of remote programming to achieve the ideal postoperative effect. Therefore, we aimed to retrospectively evaluate the effects of different programming modes on the effectiveness of STN-DBS 12 months postoperatively in patients with PD. Methods: Clinical data were collected retrospectively, before and 12 months after surgery, in 83 patients with PD. Based on the programming modes voluntarily selected by the patients during 12 months postoperatively, they were divided into three groups, namely remote programming alone, hospital programming alone, and hospital + remote programming. We compared the programming data and the effects of different programming methods on STN-DBS-related improvements 12 months postoperatively among these groups. Furthermore, we analyzed STN-DBS-related improvements at 12 months postoperatively in 76 patients. Results: The effectiveness of STN-DBS was not influenced by the three programming modes. The postoperative Movement Disorder Society Unified Parkinson's Disease Rating Scale scores did not reveal statistically significant differences between the remote alone and hospital alone programming groups, except for motor examination. The postoperative decline in the levodopa equivalent daily dose was most apparent in the hospital programming alone group. The programming frequency of the hospital + remote programming group was considerably higher than that of the remaining groups. Seventy-six patients with PD displayed good STN-DBS surgical efficacy. Conclusion: Programming modes do not influence the short-term efficacy of STN-DBS, and remote programming can yield a satisfactory surgical effect.

Analysis and Identification Genetic Effect of SARS-CoV-2 Infections to Alzheimer's Disease Patients by Integrated Bioinformatics.

BACKGROUND: COVID-19 pandemic is a global crisis which results in millions of deaths and causes long-term neurological sequelae, such as Alzheimer's disease (AD). OBJECTIVE: We aimed to explore the interaction between COVID-19 and AD by integrating bioinformatics to find the biomarkers which lead to AD occurrence and development with COVID-19 and provide early intervention. METHODS: The differential expressed genes (DEGs) were found by GSE147507 and GSE132903, respectively. The common genes between COVID-19 and AD were identified. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interactions (PPI) network analysis were carried out. Hub genes were found by cytoscape. A multivariate logistic regression model was constructed. NetworkAnalyst was used for the analysis of TF-gene interactions, TF-miRNA coregulatory network, and Protein-chemical Interactions. RESULTS: Forty common DEGs for AD and COVID-19 were found. GO and KEGG analysis indicated that the DEGs were enriched in the calcium signal pathway and other pathways. A PPI network was constructed, and 5 hub genes were identified (ITPR1, ITPR3, ITPKB, RAPGEF3, MFGE8). Four hub genes (ITPR1, ITPR3, ITPKB, RAPGEF3) which were considered as important factors in the development of AD that were affected by COVID-19 were shown by nomogram. Utilizing NetworkAnalyst, the interaction network of 4 hub genes and TF, miRNA, common AD risk genes, and known compounds is displayed, respectively. CONCLUSION: COVID-19 patients are at high risk of developing AD. Vaccination is required. Four hub genes can be considered as biomarkers for prediction and treatment of AD development caused by COVID-19. Compounds with neuroprotective effects can be used as adjuvant therapy for COVID-19 patients.

Identification of Blood-Based Glycolysis Gene Associated with Alzheimer's Disease by Integrated Bioinformatics Analysis.

BACKGROUND: Alzheimer's disease (AD) is one of many common neurodegenerative diseases without ideal treatment, but early detection and intervention can prevent the disease progression. OBJECTIVE: This study aimed to identify AD-related glycolysis gene for AD diagnosis and further investigation by integrated bioinformatics analysis. METHODS: 122 subjects were recruited from the affiliated hospitals of Ningbo University between 1 October 2015 and 31 December 2016. Their clinical information and methylation levels of 8 glycolysis genes were assessed. Machine learning algorithms were used to establish an AD prediction model. Receiver operating characteristic curve (AUC) and decision curve analysis (DCA) were used to assess the model. An AD risk factor model was developed by SHapley Additive exPlanations (SHAP) to extract features that had important impacts on AD. Finally, gene expression of AD-related glycolysis genes were validated by AlzData. RESULTS: An AD prediction model was developed using random forest algorithm with the best average ROC_AUC (0.969544). The threshold probability of the model was positive in the range of 0∼0.9875 by DCA. Eight glycolysis genes (GAPDHS, PKLR, PFKFB3, LDHC, DLD, ALDOC, LDHB, HK3) were identified by SHAP. Five of these genes (PFKFB3, DLD, ALDOC, LDHB, LDHC) have significant differences in gene expression between AD and control groups by Alzdata, while three of the genes (HK3, ALDOC, PKLR) are related to the pathogenesis of AD. GAPDHS is involved in the regulatory network of AD risk genes. CONCLUSION: We identified 8 AD-related glycolysis genes (GAPDHS, PFKFB3, LDHC, HK3, ALDOC, LDHB, PKLR, DLD) as promising candidate biomarkers for early diagnosis of AD by integrated bioinformatics analysis. Machine learning has the advantage in identifying genes.

Effect of LRRK2 G2385R Variant on Subthalamic Deep Brain Stimulation Efficacy in Parkinson's Disease in a Han Chinese Population.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for advanced Parkinson's disease (PD). The G2385R variant of LRRK2 is a risk factor for PD in Han Chinese individuals. We retrospectively compared the clinical outcomes of STN-DBS surgery between PD Han Chinese G2385R variant carriers and non-carriers. Fifty-seven PD patients with bilateral STN-DBS were enrolled, including 8 G2385R+ variant carriers (G2385R+ group) and 49 non-carriers (G2385R- group). Clinical data included Unified Parkinson's Disease Rating Scale (UPDRS) parts I to IV, levodopa equivalent daily dose (LEDD), Mini-Mental State Examination Scale (MMSE) score, and Hamilton Depression Rating Scale (HAMD) score measured prior to DBS and 12 months post-DBS. DBS settings were also recorded. All PD patients benefited from STN-DBS surgery. There were no statistical differences between the two groups in terms of motor function, daily living activities, and LEDD reductions at 12 months post-DBS. The rigidity of the post-surgical G2385R+ group was significantly improved compared with that of the G2385R- group (P = 0.045). Post-surgical voltage in the G2385R+ group was significantly higher than that in the G2385R- group (P = 0.033). STN-DBS outcomes were not influenced by the LRRK2 G2385R variant in Han Chinese patients.

Prognostic and Clinic Pathological Value of Cx43 Expression in Glioma: A Meta-Analysis.

Gap junctional intercellular communication (GJIC) composed of connexin proteins is considered vital to cancer onset and progression since 50 years ago based on Lowenstein and Kano's works, however altered expression of connexins is still a lesser known "hallmark" of cancer. Although many studies support the hypothesis that connexins are tumor suppressors, recent evidence indicates that, in some tumor types including glioma, they may play contradictory role in some specific stages of tumor progression. We thus conduct a meta-analysis to evaluate the prognostic role of Cx43 in glioma for the unanswered questions that whether Cx43 is a beneficial or insalubrity factor for glioma. Eight studies with 1,706 patients were included for meta-analysis. The results showed that Cx43 expression was a clearly negative factor with tumor grades (I 2 = 34%, P < 0.001) and beneficial for OS (n = 3, HR 2.62, 95%CI 1.47-4.68; P = 0.001). Subgroup analysis also found that Cx43 had different expression in Asian young patients vs. other groups. In conclusion, this article summarize the prognostic value of Cx43 and offer a clinical evidence for the notion that Cx43 is generally a tumor suppressor and beneficial for the patients' survival time.

Downregulation of microRNA-124 predicts poor prognosis in glioma patients.

The aim of the present study was to investigate the clinical significance of microRNA-124 (miR-124) expression in glioma. The expression levels of miR-124 were measured using quantitative real-time polymerase chain reaction (qRT-PCR) analysis. The correlation between the miR-124 levels and the clinicopathological factors of the glioma patients was analyzed. The survival curves were calculated by the Kaplan-Meier method. The influence of each variable on survival was examined by the Cox multivariate regression analysis. Compared with nonneoplastic brain tissues, the expression level of miR-124 was significantly decreased in glioma tissues (1.27 ± 0.55 versus 6.91 ± 1.06, P < 0.0001). The expression level of miR-124 was positively correlated with grade (P = 0.003) and Karnofsky performance status (KPS) score (P = 0.008). A significant difference was found that glioma patients with low miR-124 expression level had distinctly shorter OS (P = 0.001) and PFS (P = 0.002) than patients with high miR-124 expression level. Furthermore, we found that low miR-124 expression (OS P = 0.009; PFS P = 0.002) and advanced histologic grade (OS P = 0.005; PFS P = 0.001) were independent prognostic parameters indicating poor prognosis for glioma patients. Our results showed that the decreased expression of miR-124 may be associated with malignant tumor progression and poor prognosis in patients with gliomas, suggesting that miR-124 may be a novel and valuable signature for predicting the clinical outcome of patients with gliomas.

Clustering of surface NMDA receptors is mainly mediated by the C-terminus of GluN2A in cultured rat hippocampal neurons.

N-methyl-D-aspartate receptors (NMDARs) containing different GluN2 subunits play distinct roles in synaptic plasticity. Such differences may not only be determined by the channel properties, but also by differential surface distribution and synaptic localization.In the present study, using a Cy3-conjugated Fab fragment of the GFP antibody to label surface-located GluN2 subunits tagged with GFP at the N-terminus,we observed the membrane distribution patterns of GluN2A- or GluN2B-containing NMDARs in cultured rat hippocampal neurons. We found that surface NMDARs containing GluN2A, but not those containing GluN2B,were inclined to cluster at DIV7. Swapping the carboxyl termini of the GluN2 subunits completely reversed these distribution patterns. In addition, surface NMDARs containing GluN2A were preferentially associated with PSD-95. Taken together, the results of our study suggest that the clustering distribution of GluN2A containing NMDARs is determined by the GluN2AC-terminus, and its interaction with PSD-95 plays animportant role in this process.

IL-1ß-mediated repression of microRNA-101 is crucial for inflammation-promoted lung tumorigenesis.

Inflammatory stimuli clearly contribute to lung cancer development and progression, but the underlying pathogenic mechanisms are not fully understood. We found that the proinflammatory cytokine IL-1ß is dramatically elevated in the serum of patients with non-small cell lung cancer (NSCLC). In vitro studies showed that IL-1ß promoted the proliferation and migration of NSCLC cells. Mechanistically, IL-1ß acted through the COX2-HIF1α pathway to repress the expression of microRNA-101 (miR-101), a microRNA with an established role in tumor suppression. Lin28B was identified as critical effector target of miR-101 with its repression of Lin28B, a critical aspect of tumor suppression. Overall, IL-1ß upregulated Lin28B by downregulating miR-101. Interestingly, cyclooxygenase-2 inhibition by aspirin or celecoxib abrogated IL-1ß-mediated repression of miR-101 and IL-1ß-mediated activation of Lin28B along with their stimulatory effects on NSCLC cell proliferation and migration. Together, our findings defined an IL-1ß-miR-101-Lin28B pathway as a novel regulatory axis of pathogenic inflammatory signaling in NSCLC.

Growth but not photosynthesis response of a host plant to infection by a holoparasitic plant depends on nitrogen supply.

Parasitic plants can adversely influence the growth of their hosts by removing resources and by affecting photosynthesis. Such negative effects depend on resource availability. However, at varied resource levels, to what extent the negative effects on growth are attributed to the effects on photosynthesis has not been well elucidated. Here, we examined the influence of nitrogen supply on the growth and photosynthesis responses of the host plant Mikania micrantha to infection by the holoparasite Cuscuta campestris by focusing on the interaction of nitrogen and infection. Mikania micrantha plants fertilized at 0.2, 1 and 5 mM nitrate were grown with and without C. campestris infection. We observed that the infection significantly reduced M. micrantha growth at each nitrate fertilization and more severely at low than at high nitrate. Such alleviation at high nitrate was largely attributed to a stronger influence of infection on root biomass at low than at high nitrate fertilization. However, although C. campestris altered allometry and inhibited host photosynthesis, the magnitude of the effects was independent of nitrate fertilizations. The infection reduced light saturation point, net photosynthesis at saturating irradiances, apparent quantum yield, CO2 saturated rate of photosynthesis, carboxylation efficiency, the maximum carboxylation rate of Rubisco, and maximum light-saturated rate of electron transport, and increased light compensation point in host leaves similarly across nitrate levels, corresponding to a similar magnitude of negative effects of the parasite on host leaf soluble protein and Rubisco concentrations, photosynthetic nitrogen use efficiency and stomatal conductance across nitrate concentrations. Thus, the more severe inhibition in host growth at low than at high nitrate supplies cannot be attributed to a greater parasite-induced reduction in host photosynthesis, but the result of a higher proportion of host resources transferred to the parasite at low than at high nitrate levels.

CCK-8S increases the firing frequency of CCK-positive neurons and facilitates excitatory synaptic transmission in primary rat hippocampal neurons.

The neuropeptide cholecystokinin octapeptide (CCK) is involved in a variety of brain functions. In the hippocampus, most CCK is released from CCK-positive (CCK+) neurons, but the effects of CCK on CCK+ neurons are poorly understood. We employed primary hippocampal cultures to explore the modulatory effect of CCK on CCK+ neurons. CCK-8S (0.2 µM) was added to the culture medium from day in vitro 2 (DIV-2) to DIV-11. An adenovirus integrated with the CCK promoter was used to label CCK+ neurons. Whole-cell patch clamp recording was carried on to record the electrophysiology properties. The results show that: (1) CCK-8S significantly decreased membrane capacity but increased the membrane resistance (Rm) of CCK+ neurons, (2) CCK-8S increased action potential (AP) firing frequency of CCK+ neurons but did not affect the firing pattern, (3) CCK-8S facilitated CCK+ neuron excitatory synaptic transmission but attenuated inhibitory synaptic transmission, and (4) the expression of postsynaptic density-95 (PSD-95) in cultured hippocampal neurons was elevated by CCK-8S treatment. Our results demonstrate that CCK-8S significantly alters the membrane electrophysiological characteristics and synaptic activity of cultured hippocampal CCK+ neurons. These findings may enhance our understanding of the modulatory effect of CCK in the brain.

CCK-8S increased the filopodia and spines density in cultured hippocampal neurons of APP/PS1 and wild-type mice.

Cholecystokinin (CCK), a neuropeptide, is widely distributed in the brain. The function of CCK is involved in many brain functions including learning and memory, but the cellular mechanism is poorly understood. In the present study, we investigated the effect of CCK on dendritic filopodia and spines of cultured hippocampal neurons from wild-type and APP/PS1 mice. The cultured hippocampal neurons were infected with CMV-GFP (CMV promoter with green fluorescent protein) adenovirus 24h before image acquisition to display the subtle structure of dendrites. Cholecystokinin octapeptide sulfated (CCK-8S, 0.2µM) was added into the cultured solution from divided in vitro day 2 (DIV 2). A decrease of filopodia and spines density was observed in APP/PS1 mice compared with that of wild type mice. CCK-8S increased the density of filopodia and spines at DIV 7, DIV 14 and DIV 21 in hippocampal neurons of both wild-type and APP/PS1 mice. In addition, this effect was inhibited by CI988, an antagonist of CCK-2 receptor. Those results indicate that CCK-8S can influence the dendritic development and spine genesis of cultured hippocampal neurons derived from both wild-type and APP/PS1 mice. These data suggest that CCK may play an important role in learning and memory.

Effects of acupuncture treatment on depression insomnia: a study protocol of a multicenter randomized controlled trial.

BACKGROUND: More than 70% of patients with depression who see their doctors experience insomnia. Insomnia treatment is a very important link for depression treatment. Furthermore, antidepression treatment is also important for depression insomnia. In acupuncture, LU-7 (Lie Que) and KID-6 (Zhao Hai), which are two of the eight confluence points in meridian theory, are used as main points. An embedded needle technique is used, alternately, at two groups of points to consolidate the treatment effect. These two groups of points are BL-15 (Xin Shu) with BL-23 (Shen Shu) and BL-19 (Dan Shu) with N-HN-54 (An Mian). The effectiveness of these optimized acupuncture formulas is well proven in the practice by our senior acupuncturists in Guangdong Provincial Hospital of TCM. This study has been designed to examine whether this set of optimized clinical formulas is able to increase the clinical efficacy of depression insomnia treatment. METHODS/DESIGN: In this randomized controlled multicenter trial, all the eligible participants are diagnosed with depression insomnia. All participants are randomly assigned to one of two groups in a ratio of 1:1 and receive either conventional acupuncture treatment or optimized acupuncture treatment. Patients are evaluated using the Pittsburgh Sleep Quality Index(PSQI)and the Hamilton rating scale(HAMD) for depression. The use of antidepression and hypnotics drugs is also considered. Results are obtained at the start of treatment, 1 and 2 months after treatment has begun, and at the end of treatment. The entire duration of the study will be approximately 36 months. DISCUSSION: A high quality of trial methodologies is utilized in the study, and the results may provide better evidence for the effectiveness of acupuncture as a treatment for depression insomnia. The optimized acupuncture formula has potential benefits in increasing the efficacy of treating depression insomnia. TRIAL REGISTRATION: The trial was registered in Chinese Clinical Trial Register (ChiCR-TRC-00000481) on 12 August 2009.

[Chronic neck pain of cervical spondylosis treated with acupuncture and moxibustion in terms of the heart and kidney theory: a randomized controlled trial].

OBJECTIVE: To evaluate the clinical efficacy of acupuncture and moxibustion on chronic neck pain of cervical spondylosis in terms of the heart and kidney theory. METHODS: One hundred and eleven cases were randomized into a heart-kidney acupuncture group (55 cases) and a conventional acupuncture group (56 cases). In the heart-kidney acupuncture group, acupuncture was applied to Bailao (EX-HN 15), Shenmen (HT 7) and Wangu (SI 4). Afterwards, the direct moxibustion was applied to Dazhui (GV 14), Xinshu (BL 15) and Shenshu (BL 23). After moxibustion, the intradermal needling therapy was provided at Bailao (EX-HN 15), Xinshu (BL 15) and Shenshu (BL 23). In the conventional acupuncture group, acupuncture was applied to Bailao (EX-HN 15) and Zhongzhu (TE 3) at first. Afterwards, the direct moxibustion was done at Dazhui (GV 14), Bailao (EX-HN 15) and Jianzhongshu (SI 15). After moxibustion, the interdermal needling therapy was provided at Bailao (EX-HN 15) and Jianzhongshu (SI 15). The northwick park pain questionnaire (NPQ) was adopted as the main efficacy index for the evaluation. RESULTS: After the intervention and during the follow-up visit period, NPQ scores were all reduced remarkably as compared with those before the intervention for the patients in two groups (all P < 0.001), but the differences were not statistically significant in groups (all P > 0.05). By the age stratification analysis for the patients in two groups, the program in terms of the heart and kidney theory achieved the superior efficacy for the patients over 45 years old as compared with those in the conventional acupuncture group (P < 0.05, P < 0.01). By the stratification analysis of the sick duration, the program in terms of the heart and kidney theory achieved the superior efficacy for the patients with over 7 years sick duration as compared with those in the conventional acupuncture group (P < 0.05, P < 0.01). CONCLUSION: The acupuncture and moxibustion therapeutic program in terms of the heart and kidney theory achieves the superior efficacy on chronic pain of cervical spondylosis for the patients over 45 years old and with over 7 years sick duration. It is one of the optimized programs for the treatment of this disease.

The optimized acupuncture treatment for neck pain caused by cervical spondylosis: a study protocol of a multicentre randomized controlled trial.

BACKGROUND: Neck pain is one of the chief symptoms of cervical spondylosis (CS). Acupuncture is a well-accepted and widely used complementary therapy for the management of neck pain caused by CS. In this paper, we present a randomized controlled trial protocol evaluating the use of acupuncture for CS neck pain, comparing the effects of the optimized acupuncture therapy in real practice compared with sham and shallow acupuncture. METHODS/DESIGN: This trial uses a multicentre, parallel-group, randomized, sham acupuncture and shallow acupuncture, controlled single-blind design. Nine hospitals are involved as trial centres. 945 patients who meet inclusion criteria are randomly assigned to receive optimized acupuncture therapy, sham acupuncture or shallow acupuncture by a computerized central randomization system. The interventions past for 4 weeks with eight to ten treatments in total. The group allocations and interventions are concealed to patients and statisticians. The Northwick Park Neck Pain Questionnaire (NPQ) is used as the primary outcome measure, and the McGill Pain Questionnaire (MPQ) and The Short Form (36) Health Survey (SF-36) are applied as secondary outcome measures. The evaluation is performed at baseline, at the end of the intervention, and at the end of the first month and the third month during follow-up. The statistical analyses will include baseline data comparison and repeated measures of analysis of variance (ANOVA) for primary and secondary outcomes of group and time differences. Adverse events (AEs) will be reported if they occur. DISCUSSION: This trial is a multicentre randomized control trial (RCT) on the efficacy of acupuncture for CS neck pain and has a large sample size and central randomization in China. It will strictly follow the CONSORT statement and STRICTA extension guideline to report high-quality study results. By setting the control groups as sham and shallow acupuncture, this study attempts to reveal the effects of real acupuncture versus placebo or non-classic acupuncture treatment and evaluate whether classic Chinese medical acupuncture is effective on CS neck pain. This study will provide evidence for the effects of acupuncture on CS neck pain. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-TRC-00000184.

Decreased purinergic inhibition of synaptic activity in a mouse model of Niemann-Pick disease type C.

Niemann-Pick disease type C (NPC) is a progressive neurodegenerative disorder characterized by accumulation of free cholesterol in lysosomes, mainly due to a mutation in the NPC1 gene. The pathophysiological basis of the neural disorders in NPC, however, is not well understood. We found that the hippocampal field excitatory postsynaptic potential (fEPSP) was enhanced in NPC1 mutant mice. A1-receptor antagonist or adenosine degrading enzyme enhanced the fEPSP in both types of mice, but had a much weaker effect in the mutant mice, suggesting less tonic inhibition of synaptic transmission by endogenous adenosine in the mutant. Further evidence showed impaired hippocampal long term potentiation (LTP) in mutant mice. Supplement of A1 agonist N6-Cyclopentyladenosine (CPA) partially rescued the impaired LTP in mutant mice. Moreover, adenosine release from hippocampal slices was significantly decreased in the mutant. The enhanced excitatory synaptic transmission and the decreased synaptic plasticity due to the decreased adenosine release in NPC brain may partially contribute to the neural disorders of NPC disease, such as seizures, neurodegeneration, and dementia.

Radiofrequency thermocoagulation rhizotomy for recurrent trigeminal neuralgia after microvascular decompression.

BACKGROUND: Microvascular decompression (MVD) is a well accepted surgical treatment strategy for trigeminal neuralgia (TN) with satisfying long-term outcome. However, considerable recurrent patients need more effective management. The purpose of this study was to evaluate the effectiveness of radiofrequency thermocoagulation rhizotomy (RTR) on patients with recurrent TN after MVD. METHODS: Totally 62 cases of recurrent TN after MVD undergoing RTR from January 2000 to January 2010 were retrospectively evaluated. Based on surgical procedures undertaken, these 62 cases were classified into two subgroups: group A consisted of 23 cases that underwent traditional RTR by free-hand; group B consisted of 39 cases that underwent RTR under the guidance of virtual reality imaging technique or neuronavigation system. The patients in group A were followed up for 14 to 70 months (mean, 40 ± 4), and those in group B were followed up for 13 to 65 months (mean, 46 ± 7). Kaplan-Meier analyses of the pain-free survival curves were used for the censored survival data, and the log-rank test was used to compare survival curves of the two groups. RESULTS: All patients in both groups A and B attained immediate pain relief after RTR. Both groups attained good pain relief rate within the first two years of follow-up: 92.3%, 84.6% and 82.6%, 69.6% respectively (P > 0.05). After 2 years, the virtual reality or neuronavigation assisted RTR group (group B) demonstrated higher pain relief rates of 82.5%, 76.2% and 68.8% at 3, 4 and 5 years after operation respectively, while those in group A was 57.2%, 49.6%, and 36.4% (P < 0.05). Low levels of minor complications were recorded, while neither mortalities nor significant morbidity was documented. CONCLUSIONS: RTR was effective in alleviating the pain of TN cases suffering from unsuccessful MVD management. With the help of virtual reality imaging technique or neuronavigation system, the patients could attain better long-term pain relief.

[Selective radiofrequency thermocoagulation for trigeminal neuralgia].

OBJECTIVE: To study the technique and experience of selective radiofrequency thermocoagulation (SRFTC) for trigeminal neuralgia (TN) and the application of neuronavigation in SRFTC for TN. METHODS: SRFTC was performed in 3269 TN patients and neuronavigation-assisted SRFTC in 36 of them. Follow-up was carried out for over 2 years in 1722 cases. RESULTS: An excellent efficacy was achieved in 2590 cases, a fair outcome in 548 cases and no response in 131 cases. The recurrence rates at one and two years were 10.5% and 25.0% respectively. The efficacy was excellent in all cases treated by neuronavigation-assisted SRFTC. The effective rate was 96%. Neither serious complication nor death occurred in this series. CONCLUSION: SRFTC for TN is both safe and effective. And the neuronavigation technique can not only increase the surgical efficacy of SRFTCP for TN but also decrease the surgical risks.

Partial epilepsy with antecedent febrile seizures and seizure aggravation by antiepileptic drugs: associated with loss of function of Na(v) 1.1.

PURPOSE: Generalized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy in infancy (SMEI) are associated with sodium channel α-subunit type-1 gene (SCN1A) mutations. Febrile seizures and partial seizures occur in both GEFS+ and SMEI; sporadic onset and seizure aggravation by antiepileptic drugs (AEDs) are features of SMEI. We thus searched gene mutations in isolated cases of partial epilepsy with antecedent FS (PEFS+) that showed seizure aggravations by AEDs. METHODS: Genomic DNA from four patients was screened for mutations in SCN1A, SCN2A, SCN1B, and GABRG2 using denaturing high-performance liquid chromatography (dHPLC) and sequencing. Whole-cell patch clamp analysis was used to characterize biophysical properties of two newly defined mutants of Na(v) 1.1 in tsA201 cells. RESULTS: Two heterozygous de novo mutations of SCN1A (R946H and F1765L) were detected, which were proven to cause loss of function of Na(v) 1.1. When the functional defects of mutants reported previously are compared, it is found that all mutants from PEFS+ have features of loss of function, whereas GEFS+ shows mild dysfunction excluding loss of function, coincident with mild clinical manifestations. PEFS+ is similar to SMEI clinically with possible AED-induced seizure aggravation and biophysiologically with features of loss of function, and different from SMEI by missense mutation without changes in hydrophobicity or polarity of the residues. CONCLUSIONS: Isolated milder PEFS+ may associate with SCN1A mutations and loss of function of Na(v) 1.1, which may be the basis of seizure aggravation by sodium channel-blocking AEDs. This study characterized phenotypes biologically, which may be helpful in understanding the pathophysiologic basis, and further in management of the disease.

Quantitative analysis of synaptic vesicle release and readily releasable pool size in hippocampal neurons.

In central nervous system only a limited number of vesicles exist in the presynaptic terminals. The size and fusion modes of the vesicles were particularly important because of their potential impact on neuronal communications. Efficient methods were needed to analyze the recycling kinetics of synaptic vesicle and the size of readily releasable pool (RRP). In this study, fluorescent dyes with different affinity for membranes (FM1-43 with high affinity and FM2-10 with low affinity) were used to stain the functional synaptic vesicles of cultured hippocampal neurons and the kinetics of vesicle recycling was measured. The results showed that the destaining proportion was larger for FM2-10 than that for FM1-43 during the first trial, while it was greater for FM1-43 than FM2-10 during the second and third trials (first round, 93.0%+/-5.9% versus 57.9%+/-3.5% for FM2-10 and FM1-43, respectively, P<0.0001; second round, 1.4%+/-3.8% versus 24.0%+/-2.3%, P<0.0001; third round, 2.3%+/-1.6% versus 8.6%+/-1.5%, P=0.005). The results indicated that rapid endocytosis existed not only in the first round but also occurred when the vesicles were reused. Moreover, Both high-frequency stimuli and hypertonic sucrose stimuli were used to estimate the RRP sizes in the mix cultured hippocampal inhibitory neurons at 13-14 days in vitro (DIV). We found that the RRP size estimated by hypertonic sucrose stimuli [(200+/-23.0) pC] was much larger than that estimated by high-frequency stimuli [(51.1+/-10.5) pC]. One possible reason for the discrepancies in RRP estimates is that in mix cultured conditions, one neuron may receive inputs from several neurons and hypertonic sucrose stimuli will cause RRP of all those neurons release, while using dual patch recording, only the connection between two neurons was analyzed. Thus, to exclude out the impacts of inputs numbers on RRP sizes, it is more reasonable to use high-frequency stimuli to estimate the RRP size in mix cultured neurons.

The effects of drying following heat shock exposure of the desert moss Syntrichia caninervis.

Desert mosses are components of biological soil crusts (BSCs) and their ecological functions make assessment and protection of these mosses a high-ranking management priority in desert regions. Drying is thought to be useful for desert mosses surviving heat shock. In this study, we investigated the role of drying by monitoring the responses of physiological characters and asexual reproduction in the typical desert moss Syntrichia caninervis. Heat significantly decreased chlorophyll content and weakened rapid recovery of photochemical activity, and increased carotenoid content and membrane permeability. Lethal temperatures significantly destroyed shoot regeneration potential. In comparison with heat alone, drying significantly increased protonema emergence time and depressed protonema emergence area. Drying combined with heat accelerated water loss, followed by a decrease of photosynthetic activity. Drying had different influences on membrane permeability at different temperatures. When moss leaves were subjected to a combined stress of drying and heat shock, photosynthesis was maintained mainly due to the effects of drying on physiological activity although the cellular morphological integrity was affected. Drying caused opposing effects on moss physiological and reproductive characteristics. On the one hand, drying caused a positive synergistic effect with heat shock when the temperature was below 40 degrees C. On the other hand, drying showed antagonism with heat shock when the moss was subjected to temperatures higher than 40 degrees C. These findings may help in understanding the survival mechanism of dessert mosses under heat shock stress which will be helpful for the artificial reconstruction of BSCs.