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Objective:To explore the characteristics of functional connectivity (FC) and regional spontaneous brain activity in patients in a minimally-conscious state (MCS).Methods:Resting-state functional near-infrared spectroscopy (rs-fNIRS) was used. Ten minimally-conscious patients were studied along with 12 healthy counterparts as healthy controls (HC). Five minutes of rs-fNIRS data were recorded from each subject and FC and the fractional amplitude of low-frequency fluctuations (fALFFs) of 53 channels were computed using the NIRS-KIT toolbox. The results were compared between the two groups.Results:Compared with the HC group, a significant decrease was observed in the average FC strength of seventeen channel pairs after false discovery rate (FDR) correction. Most were in the right and left frontal pole, as well as the dorsolateral prefrontal lobe. Compared with the HC group, the average fALFF values of Broca′s area (channel 2), the premotor cortex and the supplementary motor cortex (channels 4, 10, and 40), the dorsolateral prefrontal lobe (channels 6, 11, 25, 39), the eye motor area of the frontal lobe (channel 12) and the frontal pole (channels 23, 27, 36) were significantly greater in the MCS group. The fluctuations of the frontal pole (channel 19) were significantly less (after FDR correction).Conclusion:In an MCS spontaneous neural activity is over-active in the prefrontal lobe and some speech- and motor-related brain regions, and coordination of the internal prefrontal functional network is disordered.
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Objective:To investigate the alterations of amplitude of low frequency fluctuation (ALFF) and functional connectivity (FC) in patients with Parkinson′s disease (PD) with apathy.Methods:From May 2016 to August 2019, PD patients and age-, gender-and education level-matched healthy controls (HC) in the First Affiliated Hospital of Nanjing Medical University were prospectively recruited. The clinical and resting-state functional MRI (rs-fMRI) data of PD patients and HC were analyzed. According to the Starkstein Apathy Scale (SAS) scores, PD patients were divided into PD with apathy (PD-A) group and PD without apathy (PD-NA) group. Rs-fMRI images were processed by DPABI based on MATLAB. ALFF values were calculated and the standard ALFF (zALFF) were obtained. ANOVA and Post-Hoc t test were performed to compare the differences in local brain activity among the three groups. The brain regions with significant different zALFF values were selected as the seeds to calculate the FC values of the whole brain. The associations between FC values and the SAS scores were performed using pearson correlation analyses. Results:A total of 75 PD patients (50 males, 25 females, aged from 44 to 88 years) and 41 HC (25 males, 16 females, aged from 54 to 72 years) were enrolled. There were 42 patients in the PD-A group and 33 patients in the PD-NA group. Significant differences were found in zALFF values among the PD-A, PD-NA and HC groups ( P<0.05). After Post-Hoc t test, compared with the HC group, zALFF values were significantly increased in the right middle frontal gyrus in the PD-A group ( P<0.05) and significantly decreased in the left precuneus in the PD-NA group; The zALFF values of the right middle frontal gyrus and left precuneus in the PD-A group were significantly higher than those in PD-NA group ( P<0.05). Brain regions with different zALFF values were used as seeds for whole-brain FC. Compared with PD-NA group, FC values between the right middle frontal gyrus and bilateral precuneus, left superior frontal gyrus and its medial side, left middle frontal gyrus, left angular, left anterior cingulate gyrus, left posterior cingulate gyrus, left parahippocampal gyrus were significantly decreased in the PD-A group ( P<0.05). Additionally, FC values of PD patients between the right middle frontal gyrus with the left precuneus, the left superior frontal gyrus and its medial side, and the left middle frontal gyrus were negatively correlated with SAS scores ( r=-0.31, -0.30 and -0.34, both P<0.05). Conclusion:PD-A and PD-NA patients have different brain functional activities and connections in the frontal lobe, parietal lobe and limbic system, suggesting that apathy in PD may be associated with the abnormal functional connections of the frontal-parietal cortical circuit and the frontal-limbic-striatal loop.
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Objective:To explore functional brain region changes and their correlation with behavioral variables based on amplitude of low-frequency fluctuation (ALFF) analysis using resting-state functional MRI (rs-fMRI) in patients with spinocerebellar ataxia type 3 (SCA3).Methods:In this prospective study, patients with SCA3 and healthy controls (HC) were recruited by Southwest Hospital, Army Medical University from May 2017 to March 2022. All subjects completed the scale for assessment and rating of ataxia (SARA), the international cooperative ataxia rating scale-posture and gait (ICARS-p&g), the rapid verbal retrieval (RVR) and Montreal cognitive assessment (MoCA). Meanwhile, the subjects underwent structural MRI and rs-fMRI scans. The MRI data were processed by DPABI software based on MATLAB. The normalized ALFF values of the two groups were compared using two-sample t-test, and the changes of ALFF values in the brain regions of SCA3 and HC groups were analyzed with the t-test of partial correlation coefficient. Spearman correlation analysis was used to evaluate the relationship between the ALFF values of abnormal brain area and the score of neurobehavioral scale in SCA3. Results:Compared with HC group, ALFF significantly increased in the left cerebellum (Crus1, Crus2, 4_5, 6, 7b, 8, 9), right cerebelum_9, left fusiform gyrus and vermis_8; while ALFF significantly decreased in the vermis_4_5 in patients with SCA3. Correlation analysis showed that ALFF values in the left cerebellar_8 were negatively correlated with RVR scores ( r=-0.293, P=0.035), ALFF values in the left cerebellar_9 were negatively correlated with MoCA scores ( r=-0.324, P=0.019), ALFF values in the right cerebellar_9 were negatively correlated with RVR scores ( r=-0.401, P=0.003) in the SCA3 patients. ALFF in the vermis_8 was positively correlated with SARA scores ( r=0.308, P=0.026) and ICARS-p&g scores ( r=0.313, P=0.024) in the SCA3 patients. Conclusion:There are significant changes in ALFF values in the cerebellum and left fusiform gyrus in patients with SCA3, and the changes of ALFF values are closely related with communication, cognitive and movement disorders.
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Objective:To explore the structural and functional alterations of related brain regions in patients after cardiopulmonary resuscitation (CPR) by brain magnetic resonance imaging (MRI).Methods:A single-center, observational, cross-sectional study design was used. Patients who had brain MRI scans during hospitalization between July 2020 and July 2021 in Emergency Department of the First Affiliated Hospital of Nanjing Medical University and had good neurologic outcomes were consecutive enrolled in this study. The healthy control (HC) group consisted of age- and sex-matched volunteers. The demographic and clinical data were recorded. The modified Rankin Scale (mRS) was used to check the recovery and degree of continued disabilities when patients performed MRI. Montreal cognitive assessment (MoCA) was used to assess cognitive functions. The analyses of voxel-based morphometry (VBM) and fractional amplitude of low-frequency fluctuation (fALFF) were conducted. After data preprocessing, comparison of gray matter volume (GMV) and fALFF values between the case group and HC group were carried out, and the information of different brain regions was obtained. Partial correlation analyses were performed to evaluate the correlation between the image parameters of different clusters and clinical parameters.Results:Totally 13 patients were enrolled in this study and 13 were in the HC group. All patients achieved good neurologic outcome; mRS was 3 in 1 case, 2 in 3 cases, and 1 in 5 cases during MEI examination. The case group showed significantly lower MoCA score compared with the HC group ( P<0.001). There were significantly decreased GMVs in the right inferior frontal gyrus, superior temporal gyrus, left superior temporal gyrus, and transverse temporal gyrus in the case group. The patients showed significantly decreased fALFF values in the left postcentral gyrus and precentral gyrus, while increased fALFF values in the right putamen than the HC group (voxel-level P<0.001 and cluster-level P<0.05 with GRF correction). In addition, mean fALFF value in the right putamen was negatively correlated with MoCA score in the case group ( r=-0.710, P=0.021). Conclusions:Patients after CPR may have GMVs and neuronal spontaneous activity changes in some brain regions, and VBM and fALFF methods can be used to objectively evaluate the impaired brain functional activity in patients after successful CPR.
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Objective To investigate tumor cell killing effect of superparamagnetic Fe3O4 nanoparticles with cubic phase through magneto-mechanical force under a low-frequency vibrating magnetic field ( VMF). Methods A kind of strong magnetic and irregular-shaped Fe3O4 nanoparticles with cubic phase was synthesized by coprecipitation method. The Fe3O4 nanoparticles were exposed to a self-developed VMF and cell killing efficiency of the Fe3O4-mediated magneto-mechanical force was investigated. Results VMF alone had no effects on cell viability. After Fe3O4 nanoparticles were added, the cell viability significantly decreased with prolonging the VMF treatment time and increasing the Fe3O4 nanoparticle concentration. Lactate dehydrogenase released by damaged cells also increased with prolonging the VMF exposure time. Conclusions The irregular-shaped Fe3O4 nanoparticles can transfer magneto-mechanical force to tumor cells under VMF, cause structural damage of cells and result in cell death. The VMF generator developed in this study has simple structure and it is safe for use and convenient for operation. The developed magnetic nanoparticles and the corresponding cancer cell killing technique have the potential for clinical transformation.
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【Objective】 To investigate the efficacy of low-frequency neuromuscular electrical stimulation in the treatment of penile hypersensitive premature ejaculation. 【Methods】 A total of 66 patients treated during Nov.2021 and Aug.2022 were randomly divided into electrical stimulation group (n=22), local anesthesia group (n=21), and combined therapy group (n=23). The electrical stimulation group received low-frequency neuromuscular electrical stimulation, 5 times a week;the local anesthesia group used compound lidocaine cream 30 minutes before sexual intercourse;the combined therapy group received both treatments. After 3-month treatment, the latency of dorsal nerve somatosensory evoked potential (DNSEP), glans penis somatosensory evoked potential (GPSEP), intravaginal ejaculation latency time (IELT), premature ejaculation diagnostic tool score (PEDT), and spouse sexual satisfaction score were collected. 【Results】 After treatment, IELT, PEDT, spouse’s sexual life satisfaction score, DNSEP and GPSEP of the three groups were significantly improved (P0.05). 【Conclusion】 Low-frequency neuromuscular electrical stimulation is effective in the treatment of penile hypersensitive premature ejaculation, and the combination of local anesthetics is more effective, which is worthy of clinical application and promotion.
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Objective To investigate the spontaneous neural activity in the brain of patients with Alzheimer' s disease (AD) used 3 indicators of resting state-functional magnetic resonance (rs-fMRI) amplitude of low frequency fluctuation (ALFF), fractional amplitude of low frequency fluctuation (fALFF) and percentage amplitude fluctuation (PerAF). Methods Totally 36 clinically diagnosed AD patients and 40 healthy volunteers were scanned by fMRI in resting state respectively. ALFF, fALFF and PerAF were used to calculate and compare the changes of brain regions between the two groups. Results Compared with the normal control group, mALFF value in AD group increased significantly in bilateral caudate nucleus, medial frontal gyrus, superior frontal gyrus, gyrus rectus, anterior cingulate gyrus, olfactive cortex, left middle frontal gyrus and inferior frontal gyrus (P<0. 05). mALFF values decreased significantly in the right middle temporal gyrus, inferior temporal gyrus, inferior occipital gyrus, middle occipital gyrus, bilateral calcarine, cuneus, lingual gyrus, superior occipital gyrus, vermis, precuneus and other regions (P<0. 05). In AD group, mfALFF value of right inferior temporal gyrus, anterior cerebellar lobe, fusiform gyrus, left superior frontal gyrus, medial frontal gyrus, middle frontal gyrus, inferior frontal gyrus, gyrus rectus and anterior cingulate gyrus increased significantly (P<0. 05); mfALFF values decreased significantly in bilateral lingual gyrus, left calcarine, cuneus, superior occipital gyrus, middle occipital gyrus and vermis (P<0. 05). In AD group, mPerAF value increased significantly in bilateral gyrus rectus, anterior cingulate gyrus, medial frontal gyrus, left superior frontal gyrus, caudate nucleus, middle frontal gyrus, inferior frontal gyrus, olfactive cortex and insula (P<0. 05); mPerAF values decreased significantly in bilateral calcarine, cuneus, superior occipital gyrus, lingual gyrus, precuneus, left fusiform gyrus, inferior occipital gyrus, right superior parietal lobule, angular gyrus, middle temporal gyrus, inferior temporal gyrus and middle occipital gyrus (P < 0. 05). Conclusion The default mode network (DMN) and visual network of AD patients are characterized by abnormal brain activity, with the most significant neural activity in the prefrontal cortex and visual cortex.
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OBJECTIVE@#Exposure to high intensity, low frequency noise (HI-LFN) causes vibroacoustic disease (VAD), with memory deficit as a primary non-auditory symptomatic effect of VAD. However, the underlying mechanism of the memory deficit is unknown. This study aimed to characterize potential mechanisms involving morphological changes of neurons and nerve fibers in the hippocampus, after exposure to HI-LFN.@*METHODS@#Adult wild-type and transient receptor potential vanilloid subtype 4 knockout (TRPV4-/-) mice were used for construction of the HI-LFN injury model. The new object recognition task and the Morris water maze test were used to measure the memory of these animals. Hemoxylin and eosin and immunofluorescence staining were used to examine morphological changes of the hippocampus after exposure to HI-LFN.@*RESULTS@#The expression of TRPV4 was significantly upregulated in the hippocampus after HI-LFN exposure. Furthermore, memory deficits correlated with lower densities of neurons and neurofilament-positive nerve fibers in the cornu ammonis 1 (CA1) and dentate gyrus (DG) hippocampal areas in wild-type mice. However, TRPV4-/- mice showed better performance in memory tests and more integrated neurofilament-positive nerve fibers in the CA1 and DG areas after HI-LFN exposure.@*CONCLUSION@#TRPV4 up-regulation induced neurofilament positive nerve fiber injury in the hippocampus, which was a possible mechanism for memory impairment and cognitive decline resulting from HI-LFN exposure. Together, these results identified a promising therapeutic target for treating cognitive dysfunction in VAD patients.
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Animais , Camundongos , Canais de Cátion TRPV/metabolismo , Filamentos Intermediários/metabolismo , Hipocampo/metabolismo , Neurônios/metabolismo , Transtornos da Memória/metabolismoRESUMO
Background: Various studies using heart rate variability (HRV) as a tool have found reduced HRV in smokers in comparison with non-smokers. However, not many studies have studied the influence of smoking on HRV in light and heavy smokers calculated by pack years. Aim and Objective: The main aim of this study was to measure and compare the influence of smoking on autonomic functions in male light and heavy cigarette smokers using HRV. Materials and Methods: The present was conducted in the Department of Physiology, Navodaya Medical College, Raichur. Permission to conduct the study was obtained from the Institutional research ethical committee. This study was conducted among male cigarette smokers with age between 20 and 50 years who were apparently healthy. The selection of subjects participating in the study was done by simple random sampling, the subjects were residents of the Raichur district. The study group subjects were divided into light and heavy smokers considering both the amount and duration of smoking calculated by pack years. HRV was recorded by using the instrument Polygraph (AD instruments, Australia, model noML870). Statistical analysis was done by independent sample t-test to compare between the groups using EPI Info Version 7.0 software. A P < 0.05 was considered as statistically significant whereas a P < 0.001 was considered as highly significant. Results: The HRV parameters indicating sympathetic function such as low frequency (LF) component, LF power expressed in normalized unit (LFnu) and LF-HF ratio were significantly increased in heavy smokers in comparison to light smokers, whereas the HRV parameters indicating parasympathetic function such as total power, high frequency (HF) component and HF power expressed in normalized unit (HFnu) were significantly decreased in heavy smokers in comparison to light smokers. Conclusion: Increased sympathetic stimulation associated with a decrease in the cardiac vagal modulation leading to imbalance in the autonomic functions was more in heavy smokers when compared to light smokers.
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Objective This study aimed at describing the frequency of rare variants of monogenic cerebral small vessel diseases (CSVD) in a cohort of patients with CSVD, and to explore its clinical relevance. Methods This study included CSVD patients visiting the Neurology Department of Peking Union Medical College Hospital(PUMCH) from March 2017 to January 2022, collecting their demographic and clinical information and DNA samples for whole-exome sequencing. Descriptive analysis and statistical analysis were conducted exploring the differences between monogenic CSVD-related gene mutation carriers and noncarriers. Results A total of 292 patients were included, 51.03% of whom carried one or more rare variants of monogenic CSVD-related genes. The most common rare low-frequency variants were located in the NOTCH3 gene (70 patients, 23.97%), followed by HTRA1 and COL4A1/COL4A2 (22 patients, 7.53%) respectively. Among the subgroup of patients without a family history of stroke (n=176), the frequency of rare variants was as high as 47.16%. Compared with non-carriers, the carriers were diagnosed at a younger age (58.76±13.71 vs. 63.46±13.21, P=0.003). No difference was found in phenotypes among single-SNP carriers, multiple-SNPs carriers, and noncarriers. Conclusions The frequency of rare mutation of monogenic CSVD-related genes were relatively high in Chinese CSVD cohort. The most common rare variant was within the NOTCH3, followed by HTRA1 and COL4A1/COL4A2 genes. For CSVD patients of unknown causes, genetic screening should not be neglected even if there is not a family history of the disease.
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【Objective】 To investigate the distribution frequency of RBC rare blood group among blood donors in Chongqing, so as to provide basic data for the establishment of regional rare blood group donor database. 【Methods】 A total of 14 805 voluntary blood donors of Chongqing Blood Center from December 2020 to May 2021 were screened for Jk(a-b-) phenotype of Kidd blood group system by urea hemolysis test and confirmed by saline agglutination test. The indirect anti-globulin test was used to screen the Fy(a-) phenotype of Duffy blood group system, s-phenotype of the MNS blood group system and k- phenotype of Kell blood group system in 1 466 O type blood donors. The polyamine test was used to screen the Di(b-) phenotype of Diego blood group system in 856 voluntary blood donors, and confirmed by anti-globulin test. 【Results】 Among the voluntary blood donors in Chongqing, the proportion of Jk(a-b-) phenotype was 0.0203% (3/14 805). The ratio of both Fy(a-b+ ) and S+ s- phenotype among type O blood donors was 0.136 4% (2/1 466), and k- phenotype was not seen. The proportion of Di(a+ b-) phenotype among 856 blood donors was 0.233 6% (2/826). 【Conclusion】 The distribution frequency of rare blood group antigens in the above five blood group systems in Chongqing voluntary blood donors presents regional characteristics.
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Objective@#To investigate the difference in behavioral characteristics among different phenotypes of attention deficit hyperactivity disorder (ADHD) using amplitude of low-frequency fluctuation (ALFF), so as to provide insights into clinical differentiation of behavioral characteristics among different phenotypes of ADHD.@*Methods@#The children with ADHD admitted to The Affiliated Hospital of Hangzhou Normal University were enrolled and classified into the inattentive type (ADHD-I), hyperactive/impulsive type (ADHD-HI) and combined type (ADHD-C). The reaction time (RT) was measured using integrated visual and auditory continuous performance test, and the mean (RT-mean) and standard deviation of RT (RT-SD) were estimated. In addition, the ALFF was calculated at 0.010 to 0.027, 0.027 to 0.073, 0.073 to 0.167 Hz, and the difference of ALFF was compared among children with different types of ADHD.@*Results@#A total of 107 children with ADHD were enrolled, including 95 boys and 12 girls, with a mean age of (8.89±1.93) years. There were 69 children with ADHD-I, 8 children with ADHD-HI and 30 children with ADHD-C. The RT-SD was significantly higher among children with ADHD-C than among children with ADHD-I [(126.003±51.619) ms vs. (97.720±45.302) ms; P=0.007]; however, there was no significant difference in RT-mean among children with various ADHD phenotypes (F=1.386, P=0.255). There was an interaction between frequency and ADHD phenotypes (F=2.754, P=0.032), and the ALFF was significantly higher among children with ADHD-C than among children with ADHD-I at 0.010 to 0.027 [(5 590.567±231.595) ms vs. (4 694.001±154.397) ms; P=0.002] and 0.073 to 0.167 Hz [(4 312.609±174.709) ms vs. (3 690.805±116.473) ms; P=0.005].@*Conclusions@#The ALFF varies in ADHD phenotypes, and there is a frequency-specific difference.
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Objective:To investigate the relationship between brain derived neurotrophic factor (BDNF) gene polymorphism and the change of grey matter volume (GMV) and fractional amplitude of low-frequency fluctuation (fALFF) in cerebral small vessel disease (CSVD) patients with subcortical ischemic depression (SID).Methods:Eighty-seven CSVD patients in the First Affiliated Hospital of Anhui Medical University were enrolled from July 2017 to November 2020 and divided into CSVD-SID group [Geriatric Depression Scale (GDS) score>10] and CSVD-non - depression group (CSVD-ND group, GDS score≤10) according to GDS. Both GMV and fALFF were calculated based on structural and functional magnetic resonance imaging data, and the interactions between SID diagnosis and BDNF gene on brain function and structure alteration were explored.Results:GMV was significantly increased in the posterior default network (pDMN; such as posterior cingulate gyrus/precuneus and middle temporal gyrus) in the CSVD-SID group compared with the CSVD-ND group. On GMV property, significant interactions between BDNF gene and SID were found in the cuneus ( F=25.50, P<0.001), precuneus lobe ( F=13.61, P<0.001) and cerebellum ( F=17.23, P<0.001). In the aspect of fALFF, the brain functional activity in the superior frontal gyrus was significantly increased in the CSVD-SID group compared with that in the CSVD-ND group (0.363±0.648 vs -0.427±0.514,cluster size=48 voxels, t=5.63, P<0.001). But there was no significant interaction between diagnosis and BDNF genotype on brain function. Conclusions:Both the GMV and fALFF were increased in CSVD-SID, mainly located in the pDMN and frontal lobe. Significant interaction was found between CSVD-SID and BDNF genotype on GMV.
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Objective:To investigate the effect of SCN1A gene polymorphism (SCN1A-rs3812718) on the alterations of spontaneous brain activity using amplitude of low-frequency fluctuations (ALFF) of MR in patients with temporal lobe epilepsy (TLE).Methods:A total of 37 TLE patients (TLE group) admitted to the Epilepsy Center of the 900th Hospital of Joint Logistic Team from March 2018 to August 2019 were retrospectively analyzed, and another 28 healthy volunteers matched for gender, age, and years of education with the TLE group were selected as the healthy control group (HC group). Sixty-five subjects were divided into four groups by genotype and diagnosis: 34 cases in AA/AG-TLE subgroup, 3 cases in GG-TLE subgroup, 20 cases in AA/AG-HC subgroup and 8 cases in GG-HC subgroup. All subjects underwent sagittal 3D-T 1WI and resting-state functional MRI using a Siemens 3.0 T Trio Tim MR scanner. Then ALFF values of the four groups were calculated using DPABI by the MATLAB 2010 platform. The ALFF values between two groups were compared by independent samples t-test. The ALFF values of different genotypes at rs3812718 locus in TLE and HC group were analyzed by multivariate analysis of variance to find out the corresponding brain regions with interaction, and then post hoc simple effect analysis was performed. Results:The ALFF values in TLE group significantly increased in left marginal lobe, left parahippocampal gyrus, left fusiform gyrus, left hippocampus, right insular lobe and right inferior temporal gyrus (Alphasim corrected P<0.001) and decreased in the left superior frontal gyrus, left middle frontal gyrus, left inferior frontal gyrus, right middle frontal gyrus, right precuneus, left precuneus, bilateral cingulate gyrus and right angular gyrus (Alphasim correction P<0.05) compared with HC group. Subjects carrying the non-risk G allele had higher ALFF values in the right inferior temporal gyrus, right fusiform gyrus, and right cerebellum than subjects carrying the risk A allele ( t=3.30, Alphasim corrected P=0.002). There was a significant interaction effect on posterior cerebellar lobe, left anterior cerebellar lobe, left inferior temporal gyrus, left superior parietal lobule and right precuneus of TLE patients with SCN1A-rs3812718 genotype. Post-hoc simple effect analysis showed that ALFF significantly increased in the left posterior cerebellar lobe, left anterior cerebellar lobe, left inferior temporal gyrus and left fusiform gyrus in GG-TLE subgroup ( t=5.97, P<0.001), but significantly decreased in the right superior parietal lobule, right precuneus, right posterior cerebellar lobe in AA/AG-TLE subgroup compared to the HC group. Compared with GG-TLE subgroup, ALFF in left posterior cerebellar lobe, left fusiform gyrus and left inferior temporal gyrus decreased in AA/AG-TLE subgroup. Conclusion:SCN1A gene polymorphism in the rs3812718 locus affects spontaneous neural activity in resting state, which may be one of the pathophysiological mechanisms of TLE.
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Objective:To observe the characteristics of resting-state brain activity in Parkinson disease (PD) patients with peak-dose dyskinesia, and to explore its pathogenesis.Methods:From March 2017 to November 2019, totally 27 PD patients with peak-dose dyskinesia (dyskinetic group), and 29 PD patients without dyskinesia (non-dyskinetic group) treated in the First Affiliated Hospital of Nanjing Medical University and 27 healthy controls from the community were recruited.Resting-state functional magnetic resonance imaging (rs-fMRI) and clinical scale data were collected.SPSS 26.0 software and REST software were used for data analysis.The whole brain amplitude of low-frequency fluctuation (ALFF) values were compared among the three groups.Correlation analysis was performed between ALFF values of the significant brain regions and the scale scores.Finally, receiver operating characteristic (ROC) curve was used to evaluate the efficacy of ALFF values of significant brain regions in identifying three groups of subjects.Results:The peak-dose dyskinetic group showed decreased ALFF in right inferior frontal gyrus(MNI: x=36, y=21, z=30; x=36, y=18, z=30)and increased ALFF in right supplementary motor area (MNI: x=9, y=0, z=69; x=6, y=-3, z=72)(all P<0.05, Alphasim correction) compared with non-dyskinetic group and healthy controls.ALFF value in right inferior frontal gyrus was negatively correlated with unified dyskinesia rating scale (UDysRS) scores ( r=-0.47, P=0.018). The ALFF value of the right inferior frontal gyrus was more effective in identifying peak-dose dyskinetic patients from non-dyskinetic patients and healthy controls, and the area under the curve of right inferior frontal gyrus were 0.881 and 0.787 (both P<0.01), respectively. Conclusion:Abnormal spontaneous brain activity in right inferior frontal gyrus and right supplementary motor area can be the neurobiological basis of peak-dose dyskinesia in PD patients.The severity of peak-dose dyskinesia is associated with abnormal brain activity of right inferior frontal gyrus.The ALFF value of right inferior frontal gyrus is a potential imaging marker for identifying peak-dose dyskinetic patient.
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OBJECTIVE@#To explore whether the effect of low-frequency pulsed electromagnetic fields (PEMFs) in promoting osteoblast mineralization and maturation is related to the primary cilia, polycystin2 (PC2) and sAC/PKA/CREB signaling pathway.@*METHODS@#We detected the expression levels of PC2, sAC, PKA, CREB and their phosphorylated proteins in primary rat calvarial osteoblasts exposed to 50 Hz 0.6 mT PEMFs for 0, 5, 15, 30, 60, 90, and 120 min. We blocked PC2 function with amiloride hydrochloride and detected the changes in the activity of sAC/PKA/CREB signal pathway and the mineralization and maturation of the osteoblasts. These examinations were repeated in the osteoblasts after specific knockdown of PC2 via RNA interference and were the co-localization of PC2, sAC, PKA, CREB and their phosphorylated proteins with the primary cilia were using immunofluorescence staining. The expressions of PC2 and the signaling proteins of sAC/PKA/CREB pathway were detected after inhibition of primary ciliation by RNA interference.@*RESULTS@#The expression levels of PC2, sAC, p-PKA and p- CREB were significantly increased in the osteoblasts after exposure to PEMFs for different time lengths (P < 0.01). Blocking PC2 function or PC2 knockdown in the osteoblasts resulted in failure of sAC/PKA/CREB signaling pathway activation and arrest of osteoblast mineralization and maturation. PC2, sAC, p-PKA and p-CREB were localized to the entire primary cilia or its roots, but PKA and CREB were not detected in the primary cilia. After interference of the primary cilia, PEMFs exposure no longer caused increase of PC2 expression and failed to activate the sAC/PKA/CREB signaling pathway or promote osteoblast mineralization and maturation.@*CONCLUSION@#PC2, located on the surface of the primary cilia of osteoblasts, can perceive and transmit the physical signals from PEMFs and promote the mineralization and maturation of osteoblasts by activating the PC2/ sAC/PKA/CREB signaling pathway.
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Animais , Ratos , Diferenciação Celular , Campos Eletromagnéticos , Osteoblastos , Osteogênese/genética , Transdução de SinaisRESUMO
It is known that low-frequency pulsed electromagnetic fields (PEMFs) can promote the differentiation and maturation of rat calvarial osteoblasts (ROBs) cultured in vitro. However, the mechanism that how ROBs perceive the physical signals of PEMFs and initiate osteogenic differentiation remains unknown. In this study, we investigated the relationship between the promotion of osteogenic differentiation of ROBs by 0.6 mT 50 Hz PEMFs and the presence of polycystin2 (PC2) located on the primary cilia on the surface of ROBs. First, immunofluorescence staining was used to study whether PC2 is located in the primary cilia of ROBs, and then the changes of PC2 protein expression in ROBs upon treatment with PEMFs for different time were detected by Western blotting. Subsequently, we detected the expression of PC2 protein by Western blotting and the effect of PEMFs on the activity of alkaline phosphatase (ALP), as well as the expression of Runx-2, Bmp-2, Col-1 and Osx proteins and genes related to bone formation after pretreating ROBs with amiloride HCl (AMI), a PC2 blocker. Moreover, we detected the expression of genes related to bone formation after inhibiting the expression of PC2 in ROBs using RNA interference. The results showed that PC2 was localized on the primary cilia of ROBs, and PEMFs treatment increased the expression of PC2 protein. When PC2 was blocked by AMI, PEMFs could no longer increase PC2 protein expression and ALP activity, and the promotion effect of PEMFs on osteogenic related protein and gene expression was also offset. After inhibiting the expression of PC2 using RNA interference, PEMFs can no longer increase the expression of genes related to bone formation. The results showed that PC2, located on the surface of primary cilia of osteoblasts, plays an indispensable role in perceiving and transmitting the physical signals from PEMFs, and the promotion of osteogenic differentiation of ROBs by PEMFs depends on the existence of PC2. This study may help to elucidate the mechanism underlying the promotion of bone formation and osteoporosis treatment in low-frequency PEMFs.
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Animais , Ratos , Fosfatase Alcalina/metabolismo , Campos Eletromagnéticos , Osteoblastos/metabolismo , Osteogênese/genética , Canais de Cátion TRPP/fisiologiaRESUMO
ObjectiveTo compare the brain imaging characteristics in patients with knee osteoarthritis (KOA) and low back pain (LBP) based on amplitude of low frequency fluctuation (ALFF) of functional magnetic resonance imaging. MethodsFrom August, 2015 to September, 2021, 16 KOA patients and 16 healthy subjects (controls 1) with similar age and gender were recruited from the communities of Fuzhou, Fujian. Other 27 patients with LBP and 32 healthy subjects (controls 2) with similar age and gender were obtained from the Openpain database. The ALFF were analyzed. KOA patients were assessed the pain with Brief Pain Inventory (BPI), and LBP patients were assessed with Visual Analogue Scale (VAS). The correlation between ALFF and pain scores was analyzed. ResultsCompared with their own controls, the ALFF decreased in the left anterior insula for both KOA and LBP patients. The ALFF decreased in the hippocampus and posterior cingulate cortex in KOA patients, while increased in LBP patients. ALFF in the left precuneus, left middle cingulate cortex and right periaqueductal gray matter decreased in KOA patients, and ALFF increased in the right precentral/postcentral gyrus. ALFF of bilateral anterior cingulate cortex, bilateral orbital anterior frontal cortex, left dorsolateral prefrontal cortex and right medial prefrontal cortex decreased in LBP patients, and ALFF increased in the right parahippocampal gyrus and right amygdala. ALFF of the left middle cingulate cortex negatively correlated with BPI score in KOA patients (r = -0.73, P = 0.003), and ALFF of the right hippocampus/amygdala positively correlated with VAS score in LBP patients (r = 0.73, P = 0.003). ConclusionThere are common and specific brain imaging features in different types of chronic pain. The alteration in the left anterior insula, hippocampus and posterior cingulate gyrus may be the common mechanism for KOA and LBP.
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Resumen Objetivo: Caracterizar las reacciones adversas medicamentosas de baja frecuencia de aparición, recibidas en la Unidad Coordinadora Provincial de Farmacovigilancia, del 2014 al 2018. Materiales y Método: Estudio observacional, descriptivo, transversal, de serie de casos en Farmacovigilancia, a partir de la notificación espontánea de sospechas de reacciones adversas en el quinquenio 2014 - 2018, en Matanzas. La información se obtuvo de la base de datos provincial de farmacovigilancia. Se describen las reacciones adversas de baja frecuencia en cuanto a sexo, edad, tipo de efecto adverso, intensidad e imputabilidad. Resultados: Se evaluaron un total de 3,407 reacciones adversas por medicamentos de baja frecuencia. Prevalecieron las clasificadas como ocasionales con 1,741 notificaciones (51.1%). El sexo femenino y los adultos fueron los más reportados. Se afectó en mayor cuantía la piel y anejos; los grupos farmacológicos más reportados fueron los analgésicos, seguido de los antimicrobianos, siendo los fármacos con mayor implicación la dipirona (7.1%) y el ibuprofeno (5.8 %). Predominaron las reacciones adversas por medicamentos de baja frecuencia moderadas (93.3%) y las probables (72.2%) según imputabilidad. Conclusiones: En Matanzas, en el período 2014-2018 se reportaron reacciones adversas a medicamentos de baja frecuencia en su mayoría ocasionales y probables en piel y anejos, producida por analgésicos y antimicrobianos en el sexo femenino y adultos, de moderada intensidad.
Abstract Objective. To characterize the adverse drug reactions of low frequency of appearance, received in the Provincial Coordinating Unit of Pharmacovigilance from 2014 to 2018. Method: Observational, descriptive, cross-sectional study of a series of cases in Pharmacovigilance, based on the spontaneous notification of suspected adverse reactions from 2014 to 2018, in Matanzas. The necessary information was obtained from the pharmacovigilance provincial database. Low-frequency adverse reactions are described in terms of sex, age, type of adverse effect, intensity and imputability, among other variables. Results: There were evaluated a total of 3407 adverse reactions due to low frequency medications. Those classified as occasional prevailed with 1,741 notifications (51.1%). Female sex and adults were the most reported. Analgesics followed by antimicrobials, and the drugs with the greatest involvement were dipyrone (7.1%) and ibuprofen (5.8%). Adverse reactions to moderate low frequency drugs (93.3%) and probable (72.2%) prevailed according to imputability. Conclusions: adverse reactions to low-frequency medications were reported in Matanzas, in the period 2014-2018, mostly occasional and probable in skin and appendages, produced by analgesics and antimicrobials in females and adults, of moderate intensity.
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Objective:To explore the effect of low frequency magnetic stimulation on myelin and inflammation in the callosum of demyelinated mice.Methods:Thirty-six 6 to 8-week-old male C57BL/6J mice were randomly divided into a control group, a cuprizone (CPZ) group and a magnetic therapy group. The CPZ group and the magnetic therapy group had demyelination induced by feeding a mixed diet containing 0.3% CPZ for 6 weeks, while the control group was given conventional food. The magnetic therapy group was given 50Hz 10mT magnetic stimulation during the 6 weeks for 20min daily, 5 days a week. The body mass of each mouse was observed every 7 days. At the end of the 6th week elevated cross maze experiments were conducted to observe any anxiety state. The myelin sheath in the corpus callosum was observed using Luxol fast blue staining and myelin basic protein (MBP) immunohistochemistry Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the corpus callosum were detected using enzyme-linked immunosorbent assays.Results:After the 6 weeks of treatment, the average body mass of the mice in the magnetic therapy group had improved significantly compared with the CPZ group. The CPZ group′s times in the elevated cross maze experiments were significantly shorter than those of the control group and also shorter than those of the magnetic therapy group. The Luxol staining showed significant myelin loss in the corpus callosum of the CPZ group, but compared with the CPZ group the average loss of myelin in the magnetic therapy group was significantly less. This was further confirmed by the MBP immunohistochemistry. Compared with the control group, the average expression of MBP in the CPZ group was significantly reduced, while in the magnetic therapy group it was significantly increased. Compared with the control group, the average TNF-α and IL-1β levels in the corpus callosum of the CPZ group increased significantly, but compared with the CPZ group the average levels in the magnetic therapy group had decreased significantly.Conclusions:Low frequency magnetic stimulation improves the body weight and anxiety state of mice. That is probably related to less myelin loss and inhibited inflammatory response in the corpus callosum.