Evaluating the link between immune characteristics and attention deficit hyperactivity disorder through a bi-directional Mendelian randomization study.

Context: Despite the recognition of attention deficit hyperactivity disorder (ADHD) as a multifaceted neurodevelopmental disorder, its core causes are still ambiguous. The objective of this study was to explore if the traits of circulating immune cells contribute causally to susceptibility to ADHD. Methods: By employing a unified GWAS summary data covering 731 immune traits from the GWAS Catalog (accession numbers from GCST0001391 to GCST0002121), our analysis focused on the flow cytometry of lymphocyte clusters, encompassing 3,757 Sardinians, to identify genetically expected immune cells. Furthermore, we obtained summarized GWAS statistics from the Psychiatric Genomics Consortium to evaluate the genetic forecasting of ADHD. The studies employed ADHD2019 (20,183 cases and 35,191 controls from the 2019 GWAS ADHD dataset) and ADHD2022 (38,691 cases and 275,986 controls from the 2022 GWAS ADHD dataset). Through the examination of genome-wide association signals, we identified shared genetic variances between circulating immune cells and ADHD, employing the comprehensive ADHD2022 dataset. We primarily utilized inverse variance weighted (IVW) and weighted median methods in our Mendelian randomization research and sensitivity assessments to evaluate diversity and pleiotropy. Results: After adjusting for false discovery rate (FDR), three distinct immunophenotypes were identified as associated with the risk of ADHD: CD33 in Im MDSC (OR=1.03, CI: 1.01~1.04, P=3.04×10-5, PFDR =0.015), CD8br NKT %T cell (OR=1.08, 95%CI: 1.04~1.12, P=9.33×10-5, PFDR =0.023), and CD8br NKT %lymphocyte (OR=1.08, 95%CI: 1.03~1.12, P=3.59×10-4, PFDR =0.066). Furthermore, ADHD showed no statistical effects on immunophenotypes. It's worth noting that 20 phenotypes exist where ADHD's appearance could diminish 85% of immune cells, including FSC-A in myeloid DC (ß= -0.278, 95% CI: 0.616~0.931, P=0.008), CD3 in CD45RA- CD4+ (ß= -0.233, 95% CI: 0.654~0.960, P=0.017), CD62L- monocyte AC (ß=0.227, 95% CI: 0.038~1.518, P=0.019), CD33 in CD33br HLA DR+ CD14dim (ß= -0.331, 95% CI: 0.543~0.950, P=0.020), and CD25 in CD39+ resting Treg (ß=0.226, 95% CI: 1.522, P=0.022), and FSC-A in monocytes (ß= -0.255, 95% CI: 0.621~0.967, P=0.234), among others. Conclusion: Studies indicate that the immune system's response influences the emergence of ADHD. The findings greatly improve our understanding of the interplay between immune responses and ADHD risk, aiding in the development of treatment strategies from an immunological perspective.

A bidirectional Mendelian randomization study about the role of morning plasma cortisol in attention deficit hyperactivity disorder.

Context: Cortisol, a hormone regulated by the hypothalamic-pituitary-adrenal (HPA) axis, has been linked to attention deficit hyperactivity disorder (ADHD). The nature of the relationship between cortisol and ADHD, and whether it is causal or explained by reverse causality, remains a matter of debate. Objective: This study aims to evaluate the bidirectional causal relationship between morning plasma cortisol levels and ADHD. Methods: This study used a bidirectional 2-sample Mendelian randomization (MR) design to analyze the association between morning plasma cortisol levels and ADHD using genetic information from the authoritative Psychiatric Genomics Collaboration (PGC) database (n = 55,347) and the ADHD Working Group of the CORtisol NETwork (CORNET) Consortium (n = 12,597). MR analyses were employed: inverse variance weighting (IVW), MR-Egger regression, and weighted medians. OR values and 95% CI were used to evaluate whether there was a causal association between morning plasma cortisol levels on ADHD and ADHD on morning plasma cortisol levels. The Egger-intercept method was employed to test for level pleiotropy. Sensitivity analysis was performed using the "leave-one-out" method, MR pleiotropy residual sum, and MR pleiotropy residual sum and outlier (MR-PRESSO). Results: Findings from bidirectional MR demonstrated that lower morning plasma cortisol levels were associated with ADHD (ADHD-cortisol OR = 0.857; 95% CI, 0.755-0.974; P = 0.018), suggesting there is a reverse causal relationship between cortisol and ADHD. However, morning plasma cortisol levels were not found to have a causal effect on the risk of ADHD (OR = 1.006; 95% CI, 0.909-1.113; P = 0.907), despite the lack of genetic evidence. The MR-Egger method revealed intercepts close to zero, indicating that the selected instrumental variables had no horizontal multiplicity. The "leave-one-out" sensitivity analysis revealed stable results, with no instrumental variables significantly affecting the results. Heterogeneity tests were insignificant, and MR-PRESSO did not detect any significant outliers. The selected single-nucleotide polymorphisms (SNPs) F were all >10, indicating no weak instrumental variables. Thus, the overall MR analysis results were reliable. Conclusion: The study findings suggest a reverse causal relationship between morning plasma cortisol levels and ADHD, with low cortisol levels associated with ADHD. No genetic evidence was found to support a causal relationship between morning plasma cortisol levels and the risk of ADHD. These results suggest that ADHD may lead to a significant reduction in morning plasma cortisol secretion.

Clinicopathological and prognostic features of subungual melanoma in situ / 中华病理学杂志

Objective: To investigate the clinicopathological characteristics, immunohistochemical profiles, molecular features, and prognosis of subungual melanoma in situ (SMIS). Methods: Thirty cases of SMIS were collected in Fudan University Shanghai Cancer Center, Shanghai, China from 2018 to 2022. The clinicopathological characteristics and follow-up data were retrospectively analyzed. Histopathologic evaluation and immunohistochemical studies were carried out. By using Vysis melanoma fluorescence in situ hybridization (FISH) probe kit, combined with 9p21(CDKN2A) and 8q24(MYC) assays were performed. Results: There were 8 males and 22 females. The patients' ages ranged from 22 to 65 years (median 48 years). All patients presented with longitudinal melanonychia involving a single digit. Thumb was the most commonly affected digit (16/30, 53.3%). 56.7% (17/30) of the cases presented with Hutchinson's sign. Microscopically, melanocytes proliferated along the dermo-epithelial junction. Hyperchromatism and nuclear pleomorphism were two of the most common histological features. The melanocyte count ranged from 30 to 185. Most cases showed small to medium nuclear enlargement (29/30, 96.7%). Pagetoid spread was seen in all cases. Intra-epithelial mitoses were identified in 56.7% (17/30) of the cases. Involvement of nailfold was found in 19 cases, 4 of which were accompanied by cutaneous adnexal extension. The positive rates of SOX10, PNL2, Melan A, HMB45, S-100, and PRAME were 100.0%, 100.0%, 96.0%, 95.0%, 76.9%, and 83.3%, respectively. FISH analysis was positive in 6/9 of the cases. Follow-up data were available in 28 patients, and all of them were alive without disease. Conclusions: SMIS mainly shows small to medium-sized cells. High melanocyte count, hyperchromatism, nuclear pleomorphism, Pagetoid spreading, intra-epithelial mitosis, nailfold involvement, and cutaneous adnexal extension are important diagnostic hallmarks. Immunohistochemistry including SOX10 and PRAME, combined with FISH analysis, is valuable for the diagnosis of SMIS.

Effect mechanism of Ma Xing Gan Shi Decoction against influenza virus from JAK2/STAT3 signaling pathway by combining network pharmacology / 中国药理学通报

Aim To explore the effect of JAK2/STAT3 signaling pathway on lung tissue injury induced by influenza A virus in combination with network pharmacology and to further explore the intervention effect of Ma Xing Gan Shi Decoction.Methods Network pharmacological method was used to screen the signal pathway enriched by Ma Xing Gan Shi Decoction on the potential target of influenza virus.BLAB/c mice were intranasally infected with influenza A virus.The mice were divided into normal control group, model control group, oseltamivir group, antiviral granule group and Ma Xing Shigan decoction group.The animals were treated with corresponding drugs for 3 and 7 days.Body weight and lung index were detected by HE for observation of the pathological changes of lung tissues.Real-time PCR(RT-PCR)was used to detect the mRNA expression levels of JAK2, STAT3, IL-1β and IL-4 in lung tissues.Western blot and ELISA were used to detect the protein expression levels of JAK2, STAT3, IL-1β and IL-4 in lung tissues.AutoDock Vina software was used to conduct molecular docking between STAT3 and target compounds.Results The main active components of Ma Xing Gan Shi Decoction had 110 intersection targets with influenza virus and were enriched in 170 signaling pathways.Ma Xing Shigan decoction could up-regulate the body weight of mice infected with influenza A virus, improve the pathological injury of lung tissues, down-regulate the lung index and the expression levels of JAK2, STAT3, IL-1β mRNA and protein in lung tissues, and up-regulate the expression levels of IL-4 mRNA and protein.STAT3 had better binding activity with glycyrrhiza chalcone A, an active compound in Ma Xing Gan Shi Decoction.Conclusions Ma Xing Gan Shi Decoction, as an effective compound prescription of traditional Chinese medicine against influenza virus, can effectively reduce pulmonary inflammation and regulate the balance of cytokines.The possible mechanism is to alleviate the lung injury caused by influenza A virus infection in mice by inhibiting the activation of JAK2/STAT3 signal pathway.

A model for predicting the probability of poor outcome at 3 months after intravenous thrombolysis for elderly patients with acute cerebral infarction / 中华老年医学杂志

Objective:To explore independent predictors for poor outcome at 3 months in elderly patients with acute cerebral infarction(ACI)treated with intravenous thrombolysis(IVT), and to develop a nomogram-based predictive model.Methods:This was a retrospective cohort study.Clinical, laboratory and imaging data of 346 elderly patients with ACI treated with IVT from January 2016 to April 2021 in our hospital were collected.Poor outcome was defined as a modified Rankin Scale(mRS)score >2 at 3 months after the stroke.Logistic regression analysis was used to screen for independent factors predicting poor outcome in elderly ACI patients treated with IVT, and a corresponding nomogram model was developed using the R software.The ROC curve, calibration plots and decision curve analysis were used to evaluate discrimination, calibration and clinical application value of the nomogram model.Results:Among 346 candidates, 109 developed a poor outcome, representing a rate of 31.5%.Logistic regression analysis showed that symptomatic hemorrhagic transformation( OR=15.647, 95% CI: 8.913-27.454), stroke severity(moderate stroke, OR=3.322, 95% CI: 1.414-7.811; moderate-severe stroke, OR=8.169, 95% CI: 4.102-16.258; severe stroke, OR=9.653, 95% CI: 5.440-17.121), stroke-associated pneumonia( OR=2.239, 95% CI: 1.134-4.420), and heart failure( OR=2.758, 95% CI: 1.424-5.336)were independent predictors for poor outcome at 3 months in elderly ACI patients treated with intravenous thrombolysis(all P<0.05). With the area under curve(AUC-ROC)value at 0.85(95% CI: 0.80-0.89), the nomogram model, which was composed of the above four predictors, demonstrated good discrimination.On the calibration plot, the mean absolute error was 0.020, indicating that the model had good calibration.Decision curve analysis revealed that the model had good clinical application value. Conclusions:The nomogram model composed of symptomatic hemorrhagic transformation, stroke severity, stroke-associated pneumonia and heart failure may predict poor outcome at 3 months in elderly ACI patients treated with IVT, with high prediction accuracy and high clinical application value.

Molecular Mechanism of "Transmission Between Lung and Brain" of Influenza and Intervention Effect of Maxing Shigantang Based on JAK1/STAT1 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo explore the molecular mechanism of "transmission between the lung and brain" of influenza based on Janus kinase 1/signal transducer and activator of transcription 1（JAK1/STAT1） signaling pathway and further investigate the intervention effect of Maxing Shigantang （MXSGT）. MethodA total of 100 SPF BALB/c mice were randomly divided into a normal group，a model group，an oseltamivir group （21.63 mg·kg-1·d-1），an antiviral granules group（3.9 g·kg-1·d-1）， and an MXSGT group（6.05 g·kg-1·d-1）， with 20 mice in each group. The pneumonia model was induced in mice except for those in the normal group by intranasal infection of influenza A virus（IAV）. Twenty-four hours after modeling，mice were treated with corresponding drugs， while those in the normal group and the model group received the same amount of normal saline by gavage， once a day for 3 and 7 days. The pathological changes in the lung and brain were observed by hematoxylin-eosin（HE）staining. The mRNA expression of IAV nucleoprotein（NP），JAK1， and STAT1 in the lung and brain was detected by real-time quantitative polymerase chain reaction（Real-time PCR）， and the protein expression of JAK1 and STAT1 in the lung and brain was detected by Western blot. Immunohistochemical method was used to detect the expression of phosphorylated（p）-STAT1 in the lung and brain tissues， and enzyme-linked immunosorbent assay（ELISA） was used to detect the serum levels of interleukin-1β（IL-1β） and interleukin-10（IL-10）. ResultCompared with the normal group， the model group showed obvious pathological changes in the lung tissues and cerebral cortex， increased relative mRNA expression of IAV NP in the lung （P<0.01）， elevated mRNA and protein expression of JAK1 and STAT1 in the lung and brain tissues （P<0.05，P<0.01），up-regulated expression level of p-STAT1 in lung tissues and cerebral cortex （P<0.05，P<0.01）， and increased serum level of IL-1β （P<0.05）. Compared with the model group， the MXSGT group showed alleviated pathological damage to lung tissues and cerebral cortex， decreased relative mRNA expression of IAV NP in lung tissues（P<0.01），reduced mRNA and protein expression levels of JAK1 and STAT1 in lung tissues and brain tissues（P<0.05，P<0.01）， and increased serum level of IL-10（P<0.01）. ConclusionThe abnormal activation of the JAK1-STAT1 signaling pathway may be one of the molecular mechanisms of "transmission between the lung and brain" of influenza. As an effective compound prescription against the influenza virus，MXSGT can alleviate the pathological damage of brain tissues in mice infected with IAV by regulating the level of cytokines mediated by this pathway.

Optimization of the extraction technology of the leaves of Dimocarpus longan by Box-Behnken response surface methodology combined with multi-index comprehensive score / 中国药房

OBJECTI VE To optimize the extraction technology of the leaves of Dimocarpus longan according to flavonoids and phenolic acids. METHODS The contents of gallic acid ，protocatechuic acid ，ethyl gallate ，quercetin，luteolin and kaempferol in the leaves of D. longan were determined by HPLC. Based on single factor test ，with the ethanol volume fraction ，solid-liquid ratio and extraction time as factors ，using comprehensive scores of the contents of above six components as indexes ，the extraction technology of the leaves of D. longan was optimized by Box-Behnken response surface methodology. RESULTS The optimal extraction technology included ethanol volume fraction of 100％，solid-liquid ratio of l ∶ 7（g/mL），extraction time of 90 min， extraction temperature of 80 ℃. After 3 times of validation tests ，the average comprehensive score was 97.54（RSD＝0.33％，n＝ 3），relative error of which with predicted score （99.05）was 1.55％. CONCLUSIONS Box-Behnken response surface methodology combined with multi-index comprehensive score can be used for the extraction technology of the leaves of D. longan ，and the optimized extraction technology is stable and feasible.

Establishment of HPLC Fingerprint of Different Polar Parts of Zhuang Medicine Calonyction muricatum and Spectrum-effect Relationship of Its Analgesic and Anti-inflammatory Effects / 中国药房

OBJECTIVE：To establish HPLC fingerprints of different polar parts of Zhuang medicine Calonyction muricatum ， and to study its spectrum-effect relationship with analgesic and anti-inflammatory effects. METHODS ：The total part ，ethyl acetate part，n-butanol part and water part of C. muricatum were prepared. HPLC fingerprints of different polar parts were established by HPLC method combined with the Similarity Evaluation System of TCM Chromatogramtic Fingerprint （2012A），and the common peaks were identified. Using writhing times and ear swelling degree in mice as analgesic and anti-inflammatory indexes ，analgesic and anti-inflammatory activity of different polar parts of C. muricatum were investigated. The correlation of the common peaks of HPLC fingerprint with analgesic and anti-inflammatory indexes was analyzed by grey correlation analysis ，bivariate correlation analysis and partial least square （PLS） method. RESULTS ： There were 11 common peaks for the different polar parts of C. muricatum ，and 5 components were identified by reference comparison，i.e. neochlorogenic acid （peak 3），chlorogenic acid （peak 5）， cryptochlorogenic acid （peak 6）， isochlorogenic acid A （peak 10），isochlorogenic acid C （peak 11）. The grey correlation analysis showed that the correlation between all common peaks and analgesic and anti- inflammatory effects were greater than 0.6 （except the correlation between peak 6 and analgesic effects ），showing correlation relationship ；the correlation of peaks 3，7 and 10 with analgesic and anti-inflammatory effects were all greater than 0.8，which was highly related. Bivariate correlation analysis showed that the correlation of peak 1，3，4，7，9，10，11 with analgesic and anti-inflammatory effects were all greater than 0.6，showing correlation relationship. PLS method showed that peaks 1，3，4，7，9，10，11 contributed greatly to playing an analgesic and anti-inflammatory role. CONCLUSIONS ：HPLC fingerprints of different polar parts of C. muricatum is established and five common peak components were identified. Neochlorogenic acid ，isochlorogenic acid A ，isochlorogenic acid C and chemical components represented by peaks 1，4，7，9 may be the pharmacodynamic substances of C. muricatum to exert analgesic and anti-inflammatory effects.

Effects of crocin on hippocampus rapid kindling epilepsy in mice / 浙江大学学报·医学版

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

Application of the two-paths double U-shaped fixer in the intravenous indwelling needle / 中国实用护理杂志

Objective To study the application of the two-paths double U-shaped fixer in clinical intravenous indwelling needle fixation. Methods A total of 420 cases using of intravenous indwelling needle from January to June 2015 were involved and divided into experimental group(210 cases) and control group(210 cases) by random digits table method. The two-paths double U-shaped fixer was applied in experimental group and the control group were used tape by Y type to fix. The incidence of returning-blood, blocking, phlebitis, slippage and the comfort between two groups were observed and compared. Results The incidence of returning-blood, blocking, phlebitis, slippage in experimental group were 6.2%(13/210), 0.5%(1/210), 0 , which were lower than those in control group 48.6%(102/210), 5.7%(12/210), 1.4%(3/210) seperately, the differences were statistically significant (χ2=117.895, P<0.01). The incidence of phlebitis levelⅠ,Ⅱ,ⅢandⅣin experimental group were 3.3%(7/210), 1.4%(3/210), 0.9%(2/210), 0, which were lower than those in control group 11.9%(25/210), 9.0%(19/210), 3.8%(8/210), 2.4%(5/210), the differences were statistically significant(Z=-5.960, P<0.01). The incidence of the comfort level 1, 2, 3 and 4 in experimental group were 92.4%(194/210), 6.2%(13/210), 1.4%(3/210), 0 individually, which were higher than those in control group 36.7%(77/210), 46.7%(98/210), 12.4%(26/210), 4.3%(9/210), the differences were statistical significant (Z=-16.228, P < 0.01). Conclusions Two-paths double U-shaped fixationis is better than Y-shaped tape fixation. To compare the venous indwelling needle fixation, two-paths double U-shaped fixer could fix more effectively and safety. At the same time, it also has advantages in convenient, observation and appearance. It could be widely used in clinical practice.

Experimental research of hair follicle reconstruction with the aid of embryonic mice dermal cells / 中华整形外科杂志

<p><b>OBJECTIVE</b>To investigate the effect of embryonic dermal signal on the hair-inductive capacity of neonatal mice dermal cells which have been amplified in vitro.</p><p><b>METHODS</b>Embryonic mice dermal cells of embryonic day 14 were added to a chamber on the back of nude mice with neonatal mice dermal cells which had been amplified in vitro for 3 days and freshly isolated neonatal mice epidermal cells. The hair regeneration was compared between the groups with or without embryonic mice dermal cells. Meanwhile, chambers with following cells respectively were constructed as controls: embryonic mice dermal cells + neonatal mice epidermal cells; freshly isolated neonatal mice dermal cells + neonatal mice epidermal cells; amplified neonatal mice dermal cells only; embryonic mice dermal cells only; freshly isolated neonatal mice dermal cells only; neonatal mice epidermal cells only.</p><p><b>RESULTS</b>The number of regenerated hairs with the aid of embryonic mice dermal cells (207 +/- 15. 948) was significantly higher than that (67 +/- 8.963) in the group without embryonic mice dermal cells (n = 3, t = 7.653, P = 0.002).</p><p><b>CONCLUSION</b>Embryonic dermal signal can enhance the hair-inductive capacity of neonatal mice dermal cells which have been amplified in vitro.</p>

Relationship between temperature and the risks of mortality in China: a Meta-analysis / 中华流行病学杂志

Objective To understand the effect of temperature on the risk of mortality and the modification effect of latitude,in China.Methods Relevant papers were searched and Meta-analysis was used to determine the exposure-response relationship for each health outcome which was associated with the exposure to temperature.Meta-regression analysis was used to evaluate the effect modification by latitude.Results Ten studies in 15 cities were included in the study.When temperature increased by one centigrade,the risks of mortality showed the following changes:deaths from non-accidental increased by 2％ (95％CI:1％,3％),from cardiovascular disease increased by 4％ (95％CI:2％,6％)and from the respiratory disease increased by 2％ (95％CI:1％,4％).As temperature decreased by one centigrade,the mortality risks of the following diseases showed the changes as:non-accidental death increased by 4％ (95％CI:2％,7％),cardiovascular disease increased by 4％ (95％CI:1％,7％) and the respiratory diseases increased by 2％ (95％CI:0％,4％).When latitude ranged from 0 to 25,26 to 30,31 to 39 degree or over 40 degrees,respectively and the temperature decreased by one centigrade,the mortality risks of the general population increased by 6.5％ (95％CI:-2.7％,15.6％),5.8％(95％ CI:2.4％,9.3％),0.8％(95％CI:0.4％,1.2％),0.5％(95％CI:-0.5％,1.5％).As temperature increased by one centigrade,mortality risk of the general population increased by 0.6％ (95％ CI:-0.3％,1.4％),1.9％ (95％ CI:0.7％,3.1％),2.0％ (95％ CI:1.0％,3.0％) and 5.8％ (95％CI:-3.2％,14.8％).As latitude increased by five degrees with high temperature,the mortality risk of general people increased by 0.3％ (95％CI:0.1％,0.8％) while decreased by 0.8％ (95％ CI:0.5％,0.9％) under low temperature.Conclusion In China,the mortality risk increased along with the changes of temperature.The adaptability to cold ness among people living in high latitude areas seemed to be stronger than those living in other areas of latitudes.Who were more vulnerable to high temperature.

Analgesic effects of chemical lumbar sympathectomy on refractory pain in the lower limbs / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the effect of chemical lumbar sympathectomy (CLS) on relieving refractory pain in the lower limbs.</p><p><b>METHODS</b>Twenty-four patients with refractory pain in the lower limbs underwent CLS under X-ray guidance, and 2 ml contrast agent was injected at 1/3 of the second L2 vertebrae (the L2 sympathetic ganglion). Lidocaine was then injected followed by injection of 7% phenol for performing CLS. The visual analog scale was used to assess the pain severity before and after CLS. The effect of CLS on relieving lower limb pain was compared with that of oral pain-relieving medication.</p><p><b>RESULTS</b>The lower limb pain was obviously relieved as shown by significantly decreased VAS scores in these patients after CLS. CLS exhibited a much more potent effect of pain relief in the lower limbs than the oral medication.</p><p><b>CONCLUSION</b>CLS produces significant analgesic effects to relieve refractory pain in the lower limbs.</p>

Effect of nano-liposome sustained elemene in inducing cell apoptosis of C6 glioma / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To study the effect of nano-liposome sustained elemene in inducing cell apoptosis of C6 glioma and to explore its influence on the expression of caspase-3 gene.</p><p><b>METHODS</b>C6 glioma cells were cultured in medium with the same amount of nano-liposome sustained elemene and common elemene respectively, also in blank medium for control. The status of cell apoptosis was determined by flow cytometry at 0, 48 h and 72 h, and the expression of Caspase-3 protein was measured simultaneously by immunohistochemistry assay.</p><p><b>RESULTS</b>Marked apoptosis presented in cells cultured in the medium with nano-liposome sustained elemene or common elemene at 48 h and 72 h, with the apoptotic rate significantly higher than that in the control. At the same time, Caspase-3 protein expression raised significantly in cells cultured in medium with either kinds of elemene, showing significant difference when compared with that in the control.</p><p><b>CONCLUSION</b>Elemene has significant apoptosis promoting and Caspase-3 protein expression inducing effect on C6 glioma cells, which could be facilitated by nano-liposome bearing.</p>

Inhibiting effect of vagal nerve stimulation to seizures in epileptic process of rats / 神经科学通报·英文版

<p><b>OBJECTIVE</b>Our previous work suggested that sensitivity of hippocampal neurons is changed in process of epileptic activities, and closely parallel to the dynamic characteristic of epileptic activity of the neurons. This study investigated the sensitivity of epileptic brain to vagal nerve stimulation (VNS) in epileptic process.</p><p><b>METHODS</b>Epileptic model was evoked by penicillin. Left vagal nerves were stimulated to inhibit the seizures induced by penicillin. The electrocorticography (ECoG) and electromyography (EMG) were recorded to analyze inhibiting effect of VNS in epileptic process.</p><p><b>RESULTS</b>It was found that VNS could inhibit the seizures caused by penicillin, and the inhibiting effect of VNS to seizures increased as the vagal nerve stimulating time prolonged. It was also found that the inhibiting effect of VNS to seizures decreased in epileptic process.</p><p><b>CONCLUSION</b>The results suggested that the sensitivity of epileptic brain to VNS was different in epileptic process. The inhibiting effect of VNS to seizure decreased as the development of seizures.</p>

Botulinum toxin type A does not affect spontaneous discharge but blocks sympathetic-sensory coupling in chronically compressed rat dorsal root ganglion neurons / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the effect of botulinum toxin type A (BTXA) on spontaneous discharge and sympathetic- sensory coupling in chronically compressed dorsal root ganglion (DRG) neurons in rats.</p><p><b>METHODS</b>In chronically compressed rat DRG, spontaneous activities of the single fibers from DRG neurons were recorded and their changes observed after BTAX application on the damaged DGR. Sympathetic modulation of the spontaneous discharge from the compressed DRG neurons was observed by electric stimulation of the lumbar sympathetic trunk, and the changes in this effect were evaluated after intravenous BTXA injection in the rats.</p><p><b>RESULTS</b>Active spontaneous discharges were recorded in the injured DRG neurons, and 47 injured DRG neurons responded to Ca2+-free artificial cerebrospinal fluid but not to BTXA treatment. Sixty-four percent of the neurons in the injured DRG responded to sympathetic stimulation, and this response was blocked by intravenously injection of BTXA.</p><p><b>CONCLUSION</b>BTXA does not affect spontaneous activities of injured DRG neurons, but blocks sympathetic-sensory coupling in these neurons.</p>

The sensitivity of neurons with non-periodic activity to sympathetic stimulation in rat injured dorsal root ganglion / 神经科学通报·英文版

Objective The relationship between firing pattern and sensitivity of neurons was studied in chronically compressed dorsal root ganglion (DRG) neurons and the Hindmarsh-Rose (HR) neuronal model. Methods Spontaneous activities from single fibers of chronically compressed DRG neurons in rats were recorded, and divided into periodic and non-periodic firing patterns. The sensitivity of the two kinds of firing pattern neuron to sympathetic stimulation (SS) was compared. Result It was found that 27.3% of periodic firing neurons and 93.2% of non-periodic firing neurons responded to SS respectively (periodic vs non-periodic, P < 0.01). The responses to SS with different stimulation time were greater non-periodic firing neurons than periodic firing neurons (P < 0.01). The non-periodic firing neurons obviously responded to SS. After the firing pattern of these neurons transformed to periodic firing pattern, their responses to SS disappeared or decreased obviously. The HR neuronal model exhibited a significantly greater response to perturbation in non-periodic (chaotic) firing pattern than in periodic firing pattern. Conclusion The non-periodic firing neurons with deterministic chaos are more sensitive to external stimuli than the periodic firing neurons.

Spontaneous discharge modulation by acetylcholine in chronically compressed rat dorsal root ganglion neurons / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the effects of acetylcholine (ACh) on spontaneous discharges of compressed rat dorsal root ganglion (DRG) neurons.</p><p><b>METHODS</b>In chronically compressed DRG model, the spontaneous discharge of a single fiber from the DRG neuron in response to ACh treatment was recorded.</p><p><b>RESULTS</b>Active spontaneous discharges were recorded in the injured DRG, and 77.9% of the injured DRG neurons responded to Ach treatment in the manner of simple excitation, or excitation followed by inhibition. The responses were enhanced with the increase of Ach concentration.</p><p><b>CONCLUSION</b>Injured DRG remains active in spontaneous discharges, which can be significantly influenced by ACh treatment.</p>

Different firing patterns induced by veratridine and aconitine in injured dorsal root ganglion neurons / 生理学报

Ectopic spontaneous activity originated from the injured dorsal root ganglion (DRG) neurons in rats was recorded through single dorsal root fiber. The firing patterns induced by veratridine and aconitine, inhibitors of inactivation gate of sodium channel operating on different binding sites, were compared. In the same neuron, veratridine (1.5 approximately 5.0 micromol/L) caused slow wave oscillations of interspike intervals (ISIs), while aconitine (10 approximately 200 micromol/L) caused tonic firing. Moreover, even if the background firing patterns were various and the reagent concentrations used were different, veratridine and aconitine still induced slow wave oscillations and tonic firing patterns, respectively. The results suggest that veratridine and aconitine induce different firing patterns in injured DRG neurons, which may relate to their inhibitory effects on different binding sites of the sodium channel.

Visually guided patch-clamp recording of spinal dorsal horn neuron's postsynaptic current evoked by primary afferent fiber / 生理学报

The authors describe here the procedures for using the gelatin half-embedding method to obtain thin spinal cord slices with attached dorsal roots and performing visually guided whole-cell patch-clamp recording of postsynaptic currents evoked by primary afferent fibers in rat spinal dorsal horn. A segment of spinal cord with attached dorsal roots was prepared and half-embedded in an agar block with 20% (w/v) gelatin. Thin spinal cord slices with attached dorsal roots were obtained with a vibratome and whole-cell patch-clamp configuration was established under the infrared observation. At the holding potential of -70 mV, spontaneous excitatory postsynaptic currents (EPSCs) and dorsal root stimulation-evoked EPSCs were recorded as inward currents. According to the conduction velocity of afferent fibers and stimulus threshold, evoked EPSCs that are mediated by A-like or C-like fibers were distinguished. At the holding potential of 0 mV, spontaneous inhibitory postsynaptic currents (IPSCs) and dorsal root stimulation-evoked IPSCs were recorded as outward currents. Using 5 micromol/L strychnine or 20 micromol/L bicuculline, GABAergic or glycinergic evoked IPSCs could be isolated. Using visual patch-clamp method synaptic transmission can be accurately assessed by measuring postsynaptic currents of the dorsal horn neurons. More importantly, with the aid of infrared observation, the incidence of failure to establish a clamp configuration can be greatly reduced and it becomes easier to make recordings from the neurons in deep dorsal horn laminae. Thus, the present research approach an effective approach to study the modulation of primary afferent synaptic transmission.