Background: and Purpose Therapeutic target selection in noninvasive brain stimulation for poststroke motor recovery typically relies on the interhemispheric inhibition model, which is effective for mildly affected patients but offers limited benefits for severely affected individuals. The mechanisms governing recovery from moderate-to-severe stroke remain poorly understood, which hinders the development of targeted interventions. Methods: We analyzed resting-state functional magnetic resonance imaging data from patients with unilateral subcortical stroke and moderate-to-severe upper limb deficits, both pre- and postintervention, along with data from healthy controls. We developed a novel dynamic lag analysis method for identifying recovery-related homotopic sensorimotor regions with altered interhemispheric interactions. To further uncover the global reorganization pathway, we developed dynamic lateralization approaches to detect large-scale functional connectivity (FC) alterations associated with the identified regions in transient lateralization states. Results: Dynamic time-lag analysis revealed significantly reduced synchronized states in the homotopic dorsal premotor cortex (PMd) post-intervention compared with pre-intervention, which correlated with motor recovery. Further dynamic lateralization analysis revealed a prolonged segregation state in patients, characterized by weakened interhemispheric and strengthened intrahemispheric interactions. In this state, patients showed decreased FC in the ipsilesional PMd and increased FC in the contralesional PMd with bilateral subcortical networks. These recoveryrelated alterations were absent in the traditional static analysis. Conclusions Dynamic analyses targeting interhemispheric interactions are valuable for understanding neural reorganization after stroke. The diminished interactions between the homotopic PMd indicate a compensatory mechanism. Importantly, a state-dependent compensatory pathway was identified, wherein the contralesional PMd assumes the functions of the ipsilesional PMd through enhanced interactions with subcortical structures, potentially guiding more effective interventions.

Objective To investigate the correlation mechanism between miR-153-3p and Nrf2 expression in human nucleus pulposus cells and intervertebral disc degeneration(IDD).Methods The oxidative damage model of nucleus pulposus cells was duplicated induced by H2O2.MiR-153-3p inhibitor-NC,si-NRF2-NC,miR-153-3p inhibitor,and si-NRF2 were transfected into nucleus pulposus cells according to the grouping require.The transfection efficiency was detected by RT-qPCR and Western blot.The cell viability was determined by the CCK-8 assay,when the intracellular reactive oxygen species(ROS)levels and the ratio of mitochondrial membrane potential decline were measured by flow cytometry,RT-qPCR was used to detect the expression levels of Nrf2,MMP-3,Col II,PINK1,Parkin,P62,and p38 MAPK.And dual luciferase reporter assay was used to measure luciferase activity.Results(1)HNPCs treated with H2O2 showed a decrease in HNPCs cell viability,a reduction in mitochondrial membrane potential,an increase in ROS levels,and a decrease in Col II expression(P<0.05).And the expression of MMP-3,P62,and p38 MAPK increased,while the expression of PINK1 and Parkin decreased.There was no significant change in Nrf2(P>0.05).(2)Inhibition of miR-153-3p expression in nucleus pulposus cells treated with H2O2 led to increased cell viability,elevated mitochondrial membrane potential,reduced ROS levels,and enhanced Col-II expression,accompanied by decreased expression of MMP-3,P62,and p38 MAPK,while simultaneously increasing the expression of PINK1,Parkin,and Nrf2(P<0.05).(3)When miR-153-3p expression was inhibited and Nrf2 expression was silenced in nucleus pulposus cells treated with H2O2,a notable decline in cell viability and mitochondrial membrane potential was observed,along with a marked increase in ROS levels.Additionally,Col-II expression decreased,whereas the expression of MMP-3,P62,and p38 MAPK increased.However,the expression of Nrf2,PINK1,and Parkin decreased(P<0.05).(4)Dual-luciferase assay analysis revealed binding sites and a binding relationship between miR-153-3p and Nrf2,indicating a negative correlation between miR-153-3p and Nrf2(P<0.05).Conclusion Inhibition of miR-153-3p expression can alleviate H2O2 induced degeneration and fibrosis of nucleus pulposus cells,activate autophagy of damaged nucleus pulposus cells,and delay apoptosis of nucleus pulposus cells.This effect is related to the PINK1/Parkin pathway and p38 MAPK inflammatory response pathway regulated by Nrf2.

Objective:To investigate the correlation between macular cherry red spot (CS) and severity of neurological manifestations in Chinese children with sialidosis (SD) type I.Methods:A evidence-based medical study. "China", "Sialidosis" and "Sialidoses" were used as Chinese and English search terms. The literature was searched in CNKI, Wanfang and PubMed. The cases were all from China and matched the diagnostic criteria. According to the presence or absence of CS in the fundus, the SD children were divided into a group with CS (+) and a group without CS (-), and the correlation between the occurrence of ocular CS and neurological manifestations was compared with meta-analysis by RevMan 5.3 software.Results:Sixty-eight studies were initially retrieved according to the search strategy, and 17 studies were finally included, and 5 studies with CS+ and CS- were meta-analyzed. Among the 43 patients, 28 were male and 15 were female, with a median age of 12 years. Visual impairment was observed in 37 cases (90.2%, 37/41, 2 cases not recorded), and CS was present in 24 cases (55.8%, 24/43). The most common neurological manifestation was myoclonus (97.7%, 42/43), followed by cerebellar ataxia (95.1%, 39/41, 2 cases not recorded) and seizures (91.4%, 32/35, 8 cases not recorded). Pathogenic NEU1 gene mutations were detected in 42 cases and one case was undocumented. The incidence of seizure in group CS+ (100%, 20/20) was higher than that in group CS- (80%, 12/15). Meta-analysis showed that there was no statistically significant difference between the incidence of myoclonus or ataxia [relative risk ( RR)=1.13, 95% confidence interval ( CI) 0.79-1.63, P=0.49] and seizure ( RR=1.13, 95% CI 0.84-2.06, P=0.24) among the children in the CS+ and CS- groups. Conclusions:The incidence of ocular CS in Chinese children with type I SD was 55.8%. There was no correlation with neurological manifestations, however the incidence of seizure was significantly higher in patients with CS than in others without CS.

Objective To explore the effects of occupational noise exposure on hypertension in Chongqing area,and to provide reference for the prevention and treatment of hypertension in noise-exposed populations.Methods Using the Chongqing key occupational disease surveillance and occupational disease hazard factor site monitoring database,the samples of adult male and female occupational noise-exposed popu-lations in Chongqing were selected by the cluster sampling,the physical examination data were collected,and the degree of hearing loss was evaluated by the binaural high-frequency mean hearing thresholds.The follow-up lasted for 3 years (2017-2019) and 5 years (2017-2021).The age,noise operation working age,BMI and blood pressure were respectively compared among the male and female respondents with different degrees of hearing loss;the Cox proportional risk regression model was adopted to analyze the relationship between de-gree of hearing loss and hypertension.Results After 3-year follow-up,the prevalence rate of hypertension in the respondents was 6.47％(308/4761),6.92％(289/4178) in males and 3.26％(19/583) in females;the de-tection rates of normal hearing,mild hearing loss and high degree of hearing loss were 46.42％,42.62％ and 10.96％ respectively.After 5-year follow-up,the prevalence rate of hypertension among the respondents was 12.44％ (431/3464),12.92％(399/3088) in males,and 8.51％(32/376) in females;the detection rates of normal hearing,mild hearing loss,and high degree of hearing loss were 64.20％,25.87％ and 9.93％ respec-tively.After 3-year,5-year follow-up,there was no significant difference in the systolic blood pressure among respondents with different degrees of hearing loss in males and females (P>0.05),but the diastolic blood pressure had significant difference (P<0.05).After adjusting the confounding factors,the 5-year risk of hy-pertension in male respondents with noise-induced mild hearing loss (binaural high-frequency mean hearing threshold 25-40 dB) was significantly increased (HR=1.25,95％CI:1.05-1.48,P<0.01).The 5-year risk of hypertension in female respondents with noise induced high degree of hearing loss (binaural high-frequency mean hearing threshold>40 dB) was significantly increased (HR=1.26,95％CI:1.10-1.44,P<0.01). Conclusion Among the populations with occupational noise exposure,the risk of developing hypertension in males with mild hearing loss is increased,and the risk of developing hypertension in males with high degree of hearing loss is increased.

AIM:To explore the protective effect and mechanism of melittin against LPS induced acute lung injury.METHODS:Mice were intratrache-ally injected with LPS(5 mg/kg)to establish acute lung injury model.The lung coefficient of mice and the lung wet-dry mass ratio were determined.The lung tissue was stained with HE.The number of in-flammatory cells and expression levels of related in-flammatory factors in bronchoalveolar lavage fluid(BALF)were detected.The activities of serum SOD,MDA and GSH were detected.The expression of TLR4,NF-κB p65 and p-NF-κB p65 in lung tissues were determined by immunohistochemistry and Western blot.RESULTS:Melittin had a protective ef-fect on LPS-induced ALI,as evidenced by significant-ly reduced lung coefficient,lung wet/dry mass ra-tio,the number of inflammatory cells and the ex-pression level of inflammatory factors in BALF,and improved pulmonary pathology(P＜0.05,P＜0.01).Compared with model group,the serum MDA level of melittin group was significantly decreased(P＜0.01),while the activities of SOD and GSH were sig-nificantly increased(P＜0.05,P＜0.01).In addition,melittin can significantly reduce the expression of TLR4,inhibit the phosphorylation of NF-κB p65,and reduce the inflammatory response(P＜0.01).CONCLUSION:Melittin can significantly improve LPS-induced ALI,and the protective effect of melit-tin is mainly related to the inhibition of TLR4/NF-κB signaling pathway and the reduction of oxidative stress and inflammation.

AIM:To explore the protective effect and mechanism of melittin against LPS induced acute lung injury.METHODS:Mice were intratrache-ally injected with LPS(5 mg/kg)to establish acute lung injury model.The lung coefficient of mice and the lung wet-dry mass ratio were determined.The lung tissue was stained with HE.The number of in-flammatory cells and expression levels of related in-flammatory factors in bronchoalveolar lavage fluid(BALF)were detected.The activities of serum SOD,MDA and GSH were detected.The expression of TLR4,NF-κB p65 and p-NF-κB p65 in lung tissues were determined by immunohistochemistry and Western blot.RESULTS:Melittin had a protective ef-fect on LPS-induced ALI,as evidenced by significant-ly reduced lung coefficient,lung wet/dry mass ra-tio,the number of inflammatory cells and the ex-pression level of inflammatory factors in BALF,and improved pulmonary pathology(P＜0.05,P＜0.01).Compared with model group,the serum MDA level of melittin group was significantly decreased(P＜0.01),while the activities of SOD and GSH were sig-nificantly increased(P＜0.05,P＜0.01).In addition,melittin can significantly reduce the expression of TLR4,inhibit the phosphorylation of NF-κB p65,and reduce the inflammatory response(P＜0.01).CONCLUSION:Melittin can significantly improve LPS-induced ALI,and the protective effect of melit-tin is mainly related to the inhibition of TLR4/NF-κB signaling pathway and the reduction of oxidative stress and inflammation.

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia seen in clinical settings, which has been associated with substantial rates of mortality and morbidity. However, clinically available drugs have limited efficacy and adverse effects. We aimed to investigate the mechanisms of action of andrographolide (Andr) with respect to AF. We used network pharmacology approaches to investigate the possible therapeutic effect of Andr. To define the role of Andr in AF, HL-1 cells were pro-treated with Andr for 1 h before rapid electronic stimulation (RES) and rabbits were pro-treated for 1 d before rapid atrial pacing (RAP). Apoptosis, myofibril degradation, oxidative stress, and inflammation were determined. RNA sequencing (RNA-seq) was performed to investigate the relevant mechanism. Andr treatment attenuated RAP-induced atrial electrophysiological changes, inflammation, oxidative damage, and apoptosis both in vivo and in vitro. RNA-seq indicated that oxidative phosphorylation played an important role. Transmission electron microscopy and adenosine triphosphate (ATP) content assay respectively validated the morphological and functional changes in mitochondria. The translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) to the nucleus and the molecular docking suggested that Andr might exert a therapeutic effect by influencing the Keap1-Nrf2 complex. In conclusions, this study revealed that Andr is a potential preventive therapeutic drug toward AF via activating the translocation of Nrf2 to the nucleus and the upregulation of heme oxygenase-1 (HO-1) to promote mitochondrial bioenergetics.
Animals ; Rabbits ; Atrial Fibrillation/metabolism* ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Signal Transduction ; NF-E2-Related Factor 2/pharmacology* ; Molecular Docking Simulation ; Oxidative Stress ; Energy Metabolism ; Mitochondria/metabolism* ; Inflammation/metabolism* ; Heme Oxygenase-1

ObjectiveTo study the expression changes of Lon protein and mitochondrial dynamics-related protein in the hippocampus of SAMP8 mice and provide a theoretical basis for the treatment of Alzheimer's disease by invigorating the spleen and supplementing Qi. MethodEight 3-month-old SAMR1 mice were used as the normal group， and 32 3-month-old SAPM8 mice were divided into model group， western medicine group （0.013 g·kg^-1）， low-dose Si Junziwan group （3.24 g·kg^-1）， and high-dose Si Junziwan group （12.56 g·kg^-1）， with 8 mice in each group. The western medicine group was gavaged with donepezil， and the Si Junziwan low- and high-dose groups were gavaged with Si Junziwan for 30 days. The positioning navigation experiment of the water maze was started on the 25^th day， and the space exploration experiment of the water maze was started on the 30^th day. On the 30^th day， the protein expression of mitofusin 2 （MFN2） was detected by immunohistochemistry， the expression of adenosine 5'-monophosphate （AMP）-activated protein kinase （AMPK） was detected by enzyme-linked immunosorbent assay （ELISA）， the content of ATP was detected by colorimetry， the microstructure of neuron mitochondria was detected by electron microscope， and the expressions of Aβ protein， Lon protein， dynamin-related protein 1 （DRP1） protein， and MFN1 protein were detected by Western blot. ResultAs compared with the normal group， the latency escape period increased， the number of crossings decreased， the expression of AMPK increased， and the content of ATP decreased in the model group. The expressions of Aβ protein and DRP1 protein increased （P<0.01）， whereas the expressions of Lon protein， MFN1 protein decreased in the model group （P<0.05，P<0.01）， and MFN2 protein decreased. The vacuolation of mitochondria increased and the cristae broke in the model group. As compared with model group， the time of the latent escape period decreased （P<0.01）， and the number of crossings increased in the low-dose and high-dose Si Junziwan groups （P<0.05）. The expression of AMPK （P<0.01） decreased， the content of ATP increased （P<0.01）， the expression of Aβ and DRP1 protein decreased （P<0.05， P<0.01）， and the expression of MFN1 protein was up-regulated （P<0.05） in high-dose Si Junziwan groups. The vacuolation was more obvious in the low-dose Si Junziwan group， whereas the vacuolation was restored and the ridge was clear in the high-dose Si Junziwan group. ConclusionSi Junziwan treats Alzheimer's disease by up-regulating the protein expression of Lon， correcting the disorder of mitochondrial division and fusion protein， and changing the memory function of SAMP8 mice.

Freshwater snail is an important biological group in aquatic ecosystem and an intermediate host of many parasites. Intestinal flora plays an important role in animal energy metabolism and resistance to pathogens. We analyzed the intestinal microbiota diversity of Radix auricularia (RA) and Planorbella trivolvis (PL) by 16S rRNA high-throughput sequencing. At the phylum level, RA had 23 phyla, including Proteobacteria (33.63%), Cyanobacteria (15.33%), Chloroflexi (13.95%), and Actinomycetes (12.99%). PL had 13 phyla, including Proteobacteria (54.88%), Bacteroidetes (28.49%), and Actinomycetes (7.65%). At the genus level, there were 445 genera in RA, including Pleurocapsa, Thiodictyon, Leptotrichia, and Nocardioides. There were 238 genera in PL, including Cloacibacterium, OM60NOR5_clade, Pseudomonas, and Rhodobacter. Ninety-three genera were the common core flora of the two snail species (all the samples were present), and 27 genera had an abundance greater than 0.5%. The structure of intestinal microbiota was significantly different between the two groups (P=0.027). We performed the functional prediction of intestinal microbiota using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt), and the results show that the KEGG functional composition of the intestinal flora of the two snails was similar, and the abundance of the amino acid metabolism, carbohydrate metabolism and membrane transport were large. In summary, the intestinal microbiota of the two snails was high in diversity and significantly different, but there were a large number of common core flora.
Animals ; Auricularia ; Ecosystem ; Fresh Water ; Gastrointestinal Microbiome/genetics* ; High-Throughput Nucleotide Sequencing ; Phylogeny ; RNA, Ribosomal, 16S/genetics* ; Snails

Objective:To investigate the diagnostic values of interleukin-22 (IL-22), interferon-γ(IFN-γ)and macrophage migration inhibition factor (MIF) in pleural effusion for tuberculosis pleurisy.Methods:From April 2018 to May 2019, a total of 77 patients including 45 cases of tuberculous pleurisy, 19 cases of malignant pleurisy, 13 cases of parapneumonia and 13 cases of healthy control in Wuxi Fifth People′s Hospital were enrolled. The levels of IL-22, IFN-γ and MIF in plasma and pleural effusion were detected by enzyme linked immunosorbent assay (ELISA). Mann-Whitney U test was used for statistical analysis.The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic values of IL-22, IFN-γ and MIF for tuberculous pleurisy. Results:The median levels of IL-22, IFN-γ, MIF and adenosine deaminase in 45 cases with pleural effusion in tuberculosis pleurisy group were 396.8 ng/L, 2 200.0 ng/L, 241.3 μg/L and 70.8 U/L, respectively, which were all significantly higher than 32 cases with non-tuberculosis pleurisy group, including 19 cases with malignant pleurisy and 13 cases with parapneumonia (52.8 ng/L, 232.3 ng/L, 179.6 μg/L and 17.0 U/L, respectively). The differences were all statistically significant ( U=179.000, 118.500, 287.000, 162.000, respectively, all P<0.05). The median levels of IL-22 and IFN-γ in plasma of tuberculosis pleurisy group were 20.0 ng/L and 45.9 ng/L, respectively, which were both higher than healthy control group (14.3 ng/L and 33.4 ng/L, respectively). The level of MIF was 96.2 μg/L, which was lower than healthy control (159.5 μg/L). The differences were all statistically significant ( U=74.000, 13.000 and 73.000, respectively, all P<0.05). The areas under ROC curve (AUC) of IL-22, IFN-γ and MIF in pleural effusion for the diagnosis of tuberculosis pleurisy were 0.876, 0.917 and 0.682, respectively.The sensitivities were 93.75%, 100.00% and 63.64%, respectively; the specificities were 82.22%, 91.11% and 65.85%, respectively. The median levels of IL-22 and IFN-γ in plasma in tuberculosis pleurisy group at two months of follow-up after anti-tuberculosis therapy were 16.0 ng/L and 33.9 ng/L, respectively, which were both lower than baseline (20.0 ng/L and 44.7 ng/L, respectively). The differences were both statistically significant ( U=2.156 and 2.221, respectively, both P<0.05). Conclusion:IFN-γ and IL-22 in pleural effusion could be used as effective indicators to identify tuberculous pleurisy, and the dynamic monitoring of IL-22 in patients′plasma could be an important biomarker in evaluating the efficacy of anti-tuberculosis treatment.