Knowledge, attitude, and practice towards enhanced recovery after surgery among patients underwent thoracoscopy surgery.

OBJECTIVE: Thoracoscopy has gained extensive utilization in managing pleural disorders, and enhanced recovery after surgery (ERAS) can improve patients' prognosis and expedite post-surgical recovery. This study aimed to investigate the knowledge, attitudes, and practices (KAP) towards ERAS among patients underwent thoracoscopy surgery. METHODS: This cross-sectional study was conducted between September 2022 and August 2023, among patients underwent thoracoscopy surgery in 6 Secondary or Tertiary hospitals in the author's area. Demographic characteristics and KAP scores were collected by questionnaires, and clinical data were extracted from medical records. RESULTS: A total of 309 valid questionnaires were collected, with 165 (53.40%) males and 202 (65.37%) aged ≤65 years old. The mean scores for KAP were 28.92±7.21 (possible range: 9-45), 53.60±6.73 (possible range: 13-65), and 43.45±5.50 (possible range: 10-50), respectively. SEM confirmed the positive associations between knowledge and attitude (ß = 0.108, P = 0.019), knowledge and practice (ß = 0.096, P = 0.004), and attitude and practice (ß = 0.438, P<0.001). However, the KAP were found not associated with prognosis. CONCLUSION: Patients underwent thoracoscopy surgery showed moderate knowledge, positive attitude, and appropriate practice towards ERAS. Preoperative education, personalized counseling, peer support groups, peer support groups, and follow-up care were recommended in further clinical practice.

Mitochondria-related HSDL2 is a potential biomarker in temporal lobe epilepsy by modulating astrocytic lipid metabolism.

Temporal lobe epilepsy (TLE) is the most prevalent type of focal epilepsy in adults. While comprehensive bioinformatics analyses have facilitated the identification of novel biomarkers in animal models, similar efforts are limited for TLE patients. In the current study, a comprehensive analysis using human transcriptomics datasets GSE205661, GSE190451, and GSE186334 was conducted to reveal differentially expressed genes related to mitochondria (Mito-DEGs). Protein-protein interaction (PPI) network and Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses were performed to identify hub genes. Additional GSE127871 and GSE255223 were utilized to establish the association with hippocampal sclerosis (HS) and seizure frequency, respectively. Single-cell RNA analysis, functional investigation, and clinical verification were conducted. Herein, we reported that the Mito-DEGs in human TLE were significantly enriched in metabolic processes. Through PPI and LASSO analysis, HSDL2 was identified as the hub gene, of which diagnostic potential was further confirmed using independent datasets, animal models, and clinical validation. Subsequent single-cell and functional analyses revealed that HSDL2 expression was enriched and upregulated in response to excessive lipid accumulation in astrocytes. Additionally, the diagnostic efficiency of blood HSDL2 was verified in Qilu cohort. Together, our findings highlight the translational potential of HSDL2 as a biomarker and provide a novel therapeutic perspective for human TLE.

Characteristics of two different immune infiltrating pyroptosis subtypes in ischemic stroke.

Background: Ischemic stroke (IS) is a serious health hazard and identified as the second leading cause of mortality around the world. However, the role of pyroptosis in the immune microenvironment regulation in IS is still unclear. Here, our study aims to elucidate the effect of pyroptosis on immune microenvironment in IS. Methods: The regulation mode of pyroptosis in IS was systematically evaluated, and its effects on immune microenvironment were explored, including infiltration of immune cells, immune response gene sets, and human leukocyte antigen (HLA) gene. The genes and drugs related to pyroptosis phenotype were also identified. An MCAO rat model was constructed, and the mRNA expression levels in the classifier model were validated by qRT-PCR. Results: The separator is composed of 11 pyroptosis genes, out of which 10 genes could distinguish between ischemic stroke and control samples. CHMP2A, CHMP4A, and NAIP genes are significantly related to immune infiltrating cells, immune response gene sets, and HLA. However, two different pyroptosis subtypes mediated by 10 pyroptosis genes were identified, which were different in immune cell abundance, HLA genes, and immune response gene sets. Furthermore, 199 genes associated with pyroptosis phenotype was identified along with the analysis of biological functions. Conclusion: These findings reveal the potential mechanism of pyroptosis in the immune microenvironment of IS, indicating that pyroptosis functions as a vital component in the complexity and diversity of the immune microenvironment in patients with IS.

Effects of stimulating single acupoint and combination acupoints on diabetic gastroparesis: A randomised controlled trial study.

Background and aim: The most effective among the acupoints remains to be determined for treating diabetic gastroparesis (DGP). This study aimed to compare single and combination acupoints for their effectiveness in DGP. Experimental procedure: A prospective, patient-assessor-blinded randomised controlled trial was designed to compare the efficacy of 8-week acupuncture at a single acupoint (Zhongwan, CV-12), combination acupoints (Zhongwan, CV-12 and Zusanli, ST-36), and a sham-acupoint, in 99 adults with DGP. The primary clinical outcome was measured using the Gastroparesis Cardinal Symptom Index (GCSI), while barium meal examination, fasting plasma glucose, the 2-h plasma glucose, short-form health survey (SF-36), and GCSI subscales were performed for evaluating secondary clinical outcomes. These results were analysed by two factorial analysis of variance (ANOVA) test, Chi-Square, Fisher Exact, Kruskal-Wallis tests and Tukey's Honest Significant Difference (HSD) test. Results: After randomization, 97 patients completed the study. GCSI scores of all groups decreased during both post-treatment and the follow-up period, they were statistically significant compared to the baseline period (p < 0.01), but there was no significant difference among the groups (p > 0.05) during the post-treatment period. GCSI scores improved more in the combination acupoints group than in the single acupoint group which was better than the sham group after treatment. During the follow-up period, the same trend was observed. Conclusions: Among patients with DGP, the combination acupoints were more beneficial compared with single and sham acupoints. Trial registration number: NCT02452489.

KAT7/HMGN1 signaling epigenetically induces tyrosine phosphorylation-regulated kinase 1A expression to ameliorate insulin resistance in Alzheimer's disease.

BACKGROUND: Epidemiological studies have revealed a correlation between Alzheimer's disease (AD) and type 2 diabetes mellitus (T2D). Insulin resistance in the brain is a common feature in patients with T2D and AD. KAT7 is a histone acetyltransferase that participates in the modulation of various genes. AIM: To determine the effects of KAT7 on insulin patients with AD. METHODS: APPswe/PS1-dE9 double-transgenic and db/db mice were used to mimic AD and diabetes, respectively. An in vitro model of AD was established by Aß stimulation. Insulin resistance was induced by chronic stimulation with high insulin levels. The expression of microtubule-associated protein 2 (MAP2) was assessed using immunofluorescence. The protein levels of MAP2, Aß, dual-specificity tyrosine phosphorylation-regulated kinase-1A (DYRK1A), IRS-1, p-AKT, total AKT, p-GSK3ß, total GSK3ß, DYRK1A, and KAT7 were measured via western blotting. Accumulation of reactive oxygen species (ROS), malondialdehyde (MDA), and SOD activity was measured to determine cellular oxidative stress. Flow cytometry and CCK-8 assay were performed to evaluate neuronal cell death and proliferation, respectively. Relative RNA levels of KAT7 and DYRK1A were examined using quantitative PCR. A chromatin immunoprecipitation assay was conducted to detect H3K14ac in DYRK1A. RESULTS: KAT7 expression was suppressed in the AD mice. Overexpression of KAT7 decreased Aß accumulation and MAP2 expression in AD brains. KAT7 overexpression decreased ROS and MDA levels, elevated SOD activity in brain tissues and neurons, and simultaneously suppressed neuronal apoptosis. KAT7 upregulated levels of p-AKT and p-GSK3ß to alleviate insulin resistance, along with elevated expression of DYRK1A. KAT7 depletion suppressed DYRK1A expression and impaired H3K14ac of DYRK1A. HMGN1 overexpression recovered DYRK1A levels and reversed insulin resistance caused by KAT7 depletion. CONCLUSION: We determined that KAT7 overexpression recovered insulin sensitivity in AD by recruiting HMGN1 to enhance DYRK1A acetylation. Our findings suggest that KAT7 is a novel and promising therapeutic target for the resistance in AD.

Generation of an induced pluripotent stem cell line (SDASi001-A) from a Schimke immune-osseous dysplasia patient with SMARCAL1 mutations.

A human induced pluripotent stem cell (iPSC) line (SDASi001-A) was generated from patient with Schimke immune-osseous dysplasia (SIOD), carrying heterozygous mutations in SMARCAL1 gene. Peripheral blood mononuclear cells (PBMCs) were reprogrammed using non-integrating delivery of OCT4, SOX2, KFL4, BCL-XL and c-MYC. The iPSC line expresses pluripotency markers, displays a normal karyotype, and has the ability to differentiate into cells of three germ layers in vitro. This iPSC line represents a valuable cell model for SIOD in humans.

Environmental impacts, human health, and energy consumption of nitrogen management for maize production in subtropical region.

Over-application of fertilizers could not improve crop yield and agronomic efficiency, but result in increasing nitrogen (N) surplus and adverse effects on the ecosystem sustainability. Although some previous studies have addressed one or a few environmental aspects in crop production, an integrated assessment for the effects of N fertilizer on multiple environmental impacts, and the optional steps of normalization and weighting is required. A consecutive 2-year plot-based field experiment was conducted with five N fertilizer levels (0, 90, 180, 270, and 360 kg N ha-1) in maize production at three sites in Southwest China, to evaluate the environmental performance and sustainability through joint use of life cycle assessment (LCA) and energy consumption analysis. Results demonstrated that the optimal N rate (180 kg N ha-1) showed greater potential for maintaining high yield (achieved 86% of the yield potential) and reducing the global warming (- 31%), acidification (- 47%), eutrophication (- 44%) compared to farmers' practice, and energy depletion potentials, by reducing pollutants emission during the production and transportation of N fertilizer and Nr losses at farm stage. Optimal N treatment indirectly reduced the land use, life-cycle human toxicity, aquatic eco-toxicity, and terrestrial eco-toxicity potentials by improving grain yield and agronomic efficiency. In addition, the optimal N treatment reduced the energy consumption by enhancing the energy use efficiency (EUE) (+ 74%) and reducing non-renewable energy form (- 45%) than the farmer's practice. This study will provide comprehensive information for both scientists and farmers involved in maize production and N management in subtropical region.

CRISPR Detection and Research on Screening Mutant Gene TTN of Moyamoya Disease Family Based on Whole Exome Sequencing.

Moyamoya disease (MMD) has a high incidence in Asian populations and demonstrates some degree of familial clustering. Whole-exome sequencing (WES) is useful in establishing key related genes in familial genetic diseases but is time-consuming and costly. Therefore, exploring a new method will be more effective for the diagnosis of MMD. We identified familial cohorts showing MMD susceptibility and performed WES on 5 affected individuals to identify susceptibility loci, which identified point mutation sites in the titin (TTN) gene (rs771533925, rs559712998 and rs72677250). Moreover, TTN mutations were not found in a cohort of 50 sporadic MMD cases. We also analyzed mutation frequencies and used bioinformatic predictions to reveal mutation harmfulness, functions and probabilities of disease correlation, the results showed that rs771533925 and rs72677250 were likely harmful mutations with GO analyses indicating the involvement of TTN in a variety of biological processes related to MMD etiology. CRISPR-Cas12a assays designed to detect TTN mutations provided results consistent with WES analysis, which was further confirmed by Sanger sequencing. This study recognized TTN as a new familial gene marker for moyamoya disease and moreover, demonstrated that CRISPR-Cas12a has the advantages of rapid detection, low cost and simple operation, and has broad prospects in the practical application of rapid detection of MMD mutation sites.

Identification of a de novo splicing mutation in the CSF1R gene in a Chinese patient with hereditary diffuse leukoencephalopathy with spheroids.

OBJECTIVE: To report a de novo splicing mutation in the CSF1R gene in a patient with hereditary diffuse leukoencephalopathy with spheroids (HDLS). METHODS: A 42-year-old Chinese woman with constant weakness on her left lower extremity was recruited in the current study. Detail medical history and clinical characteristics were reviewed. Brain magnetic resonance imaging (MRI), whole-exome sequencing, and Sanger sequencing were performed with bioinformatics analysis. RESULTS: The Chinese HDLS patient with no HDLS family history exhibited a de novo splicing mutation (c.1754-10 T > A) in the CSF1R gene. This mutation was located at the splice site of intron 12 and resulted in the skipping of exon 13 from the CSF1R mRNA. This finding constitutes the first de novo splicing mutation ever reported in HDLS. Furthermore, MRI abnormalities had been reported at least 6 months prior to the onset of the patient's clinical phenotype. CONCLUSION: Our study indicates that the diagnosis of HDLS should be considered even in the absence of a family history and can help deepen the clinical and genetic understanding of HDLS.

The Roles of Exosomes as Future Therapeutic Agents and Diagnostic Tools for Glioma.

Glioma is a common type of tumor originating in the brain. Glioma develops in the gluey supporting cells (glial cells) that surround and support nerve cells. Exosomes are extracellular vesicles that contain microRNAs, messenger RNA, and proteins. Exosomes are the most prominent mediators of intercellular communication, regulating, instructing, and re-educating their surrounding milieu targeting different organs. As exosomes' diameter is in the nano range, the ability to cross the blood-brain barrier, a crucial obstacle in developing therapeutics against brain diseases, including glioma, makes the exosomes a potential candidate for delivering therapeutic agents for targeting malignant glioma. This review communicates the current knowledge of exosomes' significant roles that make them crucial future therapeutic agents and diagnostic tools for glioma.

Effect of TRPM2-Mediated Calcium Signaling on Cell Proliferation and Apoptosis in Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is the sixth leading cause of death due to cancer, indicating that finding new therapeutic targets or approaches for ESCC treatment is imperative. Transient Receptor Potential cation channel subfamily M, member 2 (TRPM2) is a calcium-permeable, nonselective cation channel that responds to reactive oxygen species (ROS), which are found in the tumor microenvironment and are important regulators of tumorigenesis, cell proliferation, apoptosis, and the therapeutic response. Here, we used immunohistochemical analysis of tumor tissue derived from patients with ESCC to find that the TRPM2 channel protein expression level was increased in tumor tissue compared with adjacent normal tissue. Intracellular calcium concentration measurements, western blotting, and ROS and cell viability assays were used with a human ESCC cell line (TE-1 cells) to find that TRPM2 participated in the ROS hydrogen peroxide-induced increase in intracellular calcium. This increased calcium inhibited cell proliferation and enhanced apoptosis. Pretreatment of cells with the anticancer agent 5-fluorouracil (5-FU) significantly increased ROS production, which potentiated TRPM2-mediated calcium signaling, decreased cell proliferation, and increased apoptosis in TE-1 cells, suggesting that the therapeutic effect of 5-FU in ESCC cells may be mediated by the TRPM2 channel-mediated calcium influx. These findings offer a potential treatment target and provide mechanistic insight into the therapeutic effects of 5-FU in patients with ESCC.

The efficacy and safety of antiepileptics in the prophylaxis of pediatric migraine: the meta-analysis of randomized controlled trials.

BACKGROUND: Migraine is the most common primary headache among children and adolescents. The aim of this meta-analysis was to evaluate the efficacy and safety of antiepileptic drugs in the prevention of pediatric migraine. METHODS: PubMed, Cochrane Library, EMBASE and Chinese National Knowledge Infrastructure (CNKI) databases were searched for eligible published RCTs from January 1970 to June 2020. Migraine frequency and ≥50% response rate were measured as the efficacy outcomes. We used "Risk of Bias" tool for quality assessment and RevMan5.3 software for statistical analysis. RESULTS: Four articles containing 7 RCTs with 794 participants compared the efficacy of AEDs with placebo. Four RCTs assessed topiramate vs. placebo and 3 RCTs evaluated divalproex sodium extended-release (DVPX ER) vs. placebo. The results demonstrated that children receiving antiepileptic drugs had a significant advantage in remitting the mean monthly migraine days compared to those who received placebo, with an MD of -0.48 (n=930, 95% CI: -0.84 to -0.12, Z=2.60, P=0.009). Topiramate significantly reduced monthly migraine days (MD =-0.70, n=489, 95% CI: -1.16 to -0.25, Z=3.01, P=0.003) but failed to improve the ≥50% response rate (MD =-1.50, n=489, 95% CI: 0.70 to 3.22, Z=1.05, P=0.30). DVPX ER did not significantly reduce monthly headache frequency (n=441, 95% CI: -0.70 to 0.47, Z=0.38, P=0.70) or improve the ≥50% response rate (n=441, 95% CI: 0.59 to 1.25, Z=0.82, P=0.41) compared with placebo. Topiramate and DVPX ER were related to higher rates of side effects and adverse reactions. DISCUSSION: Topiramate can reduce monthly headache days in children and adolescents with migraine. However, it failed to improve the ≥50% response rate. DVPX ER showed no difference from placebo in the prophylactic treatment pediatric migraine. Side effects seemed to be more frequent in topiramate and DVPX ER treated children but generally well-tolerated.

Aberrant hypermethylation induced downregulation of antisense lncRNA STXBP5-AS1 and its sense gene STXBP5 correlate with tumorigenesis of glioma.

AIMS: The expression of antisense lncRNA STXBP5-AS1 and its sense gene STXBP5 were found to be downregulated in glioma by RNA sequencing; however, the function and mechanism of both two genes in the development of glioma have not been studied. MATERIALS AND METHODS: QRT-PCR and western blot were used to determine the transcriptional and translational levels of moleculars. MSP and BSP assays were used to evaluate the methylation status of promoter CpG island. MTT, EdU, flow cytometry, and transwell assays were used to reveal biological effects. The in vivo mice model was used to validate the role of target genes in tumorigenesis. KEY FINDINGS: The mRNA and protein expression of STXBP5 was significantly downregulated in glioma tissues and positively correlated with prognosis. STXBP5-AS1 was downregulated in glioma cells and tissues, and associated with tumor size and clinical stages. Both of two genes were significantly restored in cells treatment with 5-Aza. The promoter CpG island of STXBP5/STXBP5-AS1 was hypermethylated in glioma cells, but partially methylated in NHA cells. We found that promoter methylation frequency was significantly higher in glioma tissues. Functionally, overexpression of STXBP5 and STXBP5-AS1 inhibited cell proliferation, migration, and invasion and promoted apoptosis in vitro, whereas depletion of STXBP5 and STXBP5-AS1 showed opposite effects. Both the mRNA and protein expression of STXBP5 were positively regulated by STXBP5-AS1. Ectopic expression of STXBP5 and STXBP5-AS1 suppressed tumor formation in vivo. SIGNIFICANCE: Our findings suggested that epigenetically silenced STXBP5-AS1 and STXBP5 might act as novel tumor suppressors of glioma.

Voltage-dependent anion channels mediated apoptosis in refractory epilepsy.

The purpose of this study was to investigate the role of voltage-dependent anion channel (VDAC) in mitochondria-mediated apoptosis of neurons in refractory epilepsy. Western blot analyses were carried out to detect the changes in cytochrome C, caspase 9, Bax, and Bcl-2. TUNEL assays were also carried out to investigate cell apoptosis under the upregulation and downregulation of VDAC1 with or without Bax or Bcl-2. VDAC1 induced Bax, Bcl-2, and caspase 9, increasing the release of cytochrome C. VDAC1 played an essential role in the apoptotic cell death of refractory epilepsy. It is concluded that VDAC1 plays an important role in refractory epilepsy and could be a possible therapeutic target of anti-epileptic drugs. The current study provides a new understanding of the possible mechanisms of refractory epilepsy.

Immunoproteasome is up-regulated in rotenone-induced Parkinson's disease rat model.

The study was to investigate whether immunoproteasome (i-proteasome) and its downstream pathway are related to the pathogenesis of Parkinson's disease (PD). Rats were treated with rotenone showed significant weight loss and dyskinesia, which is consistent with the degeneration of TH-positive neurons and the activation of Iba-1-positive microglia/macrophages. Two major catalytic subunits of i-proteasome (PSMB9 and PSMB8) were seldom expressed in rat substantia nigra (SN) under normal condition, but they were significantly up-regulated with the release of TNF-α and IFN-γ after exposure to rotenone. In addition, compared with control group, the antigen presentation-related proteins antigen peptide transporter (TAP) 1, TAP2, major histocompatibility complex (MHC)-I and MHC-II levels were significantly up-regulated in rotenone group, which was in line with the accumulation of α-syn. These findings suggested that i-proteasome and antigen presentation pathways (related proteins) were upregulated by rotenone in a PD rat model.

Predicting SSRI-Resistance: Clinical Features and tagSNPs Prediction Models Based on Support Vector Machine.

BACKGROUND: A large proportion of major depressive patients will experience recurring episodes. Many patients still do not response to available antidepressants. In order to meaningfully predict who will not respond to which antidepressant, it may be necessary to combine multiple biomarkers and clinical variables. METHODS: Eight hundred fifty-seven patients with recurrent major depressive disorder who were followed up 3-10 years involved 32 variables including socio-demographic, clinical features, and SSRIs treatment features when they received the first treatment. Also, 34 tagSNPs related to 5-HT signaling pathway, were detected by using mass spectrometry analysis. The training samples which had 12 clinical variables and four tagSNPs with statistical differences were learned repeatedly to establish prediction models based on support vector machine (SVM). RESULTS: Twelve clinical features (psychomotor retardation, psychotic symptoms, suicidality, weight loss, SSRIs average dose, first-course treatment response, sleep disturbance, residual symptoms, personality, onset age, frequency of episode, and duration) were found significantly difference (P< 0.05) between 302 SSRI-resistance and 304 SSRI non-resistance group. Ten SSRI-resistance predicting models were finally selected by using support vector machine, and our study found that mutations in tagSNPs increased the accuracy of these models to a certain degree. CONCLUSION: Using a data-driven machine learning method, we found 10 predictive models by mining existing clinical data, which might enable prospective identification of patients who are likely to resistance to SSRIs antidepressant.

The Efficacy and Safety of Topiramate in the Prevention of Pediatric Migraine: An Update Meta-Analysis.

Background: Migraine is the most common acute primary headache in children and adolescents. In 2014, topiramate became the first preventive drug for migraine, approved by the Food and Drug Administration (FDA) for adolescents. This meta-analysis was aimed to evaluate the efficacy and safety of topiramate in the prevention of pediatric migraine. Methods: We searched the PubMed, EMBASE, Cochrane Library, and Chinese National Knowledge Infrastructure (CNKI) databases up to June 2019 for eligible randomized controlled trials (RCTs). The primary outcomes were mean migraine days per month, ≥50% reduction rate, and Pediatric Migraine Disability Assessment Scale (PedMIDAS) scores. RevMan5.3 software was performed for statistical analysis. Results: Overall, 5 RCTs recruiting 531 patients (6-17 years of age) were included in the meta-analysis. The target dose of topiramate was 2 mg/kg (the maintenance phase was 12 weeks), 2-3 mg/kg, 50 mg/day, and 100 mg/day (maintaining for 16 weeks), respectively, in the included studies. Our results demonstrate that participants receiving topiramate had a significant advantage in remitting the monthly migraine days than those receiving placebo, with a mean difference (MD) of -0.78 (n = 531; 95% CI, -1.23 to -0.32; Z = 3.37; P = 0.0008). Topiramate could also reduce the mean PedMIDAS scores (n = 238; 95% CI, -16.53 to -0.49; Z = 2.43; P = 0.04). However, there was no significant difference in the percentage of patients experiencing a ≥50% reduction in monthly headache days between topiramate and placebo groups (n = 531; 95% CI, 0.94-1.77; Z = 1.58; P = 0.11). Topiramate was associated with higher rates of side effects such as weight decrease (n = 395; 95% CI, 2.73-22.98; Z = 3.81; P < 0.01) and paresthesia (n = 531; 95% CI, 3.05-13.18; Z = 4.94; P < 0.01). Conclusions: Topiramate can significantly decrease monthly headache days and migraine-related burden in migraine patients <18 years old. However, it failed to increase 50% response rate. Adverse events seem to be more frequent in topiramate-treated children.

Peripheral Humoral Immune Response Is Associated With the Non-motor Symptoms of Parkinson's Disease.

BACKGROUND: Non-motor symptoms are common in Parkinson's disease (PD) and can even be used as part of the supportive criteria for diagnosis. Chronic inflammation is involved in every stage of PD. Disorders of the immune system affect the peripheral blood. Whether the humoral immune response is associated with the non-motor symptoms of PD remains unknown. METHODS: Mann-Whitney tests and Bonferroni correction were used to compare the serum levels of IgG, IgA, IgM, C3, and C4 between 180 sporadic PD patients and 187 healthy controls. Multiple regression models were conducted to assess the associations among these indicators of humoral immunity and the clinical features of PD patients. RESULTS: Male PD patients had lower levels of C3 and C4 than healthy controls [0.87 (0.22) vs. 0.96 (0.19); 0.19 (0.06) vs. 0.22 (0.07), respectively, Pc < 0.01] and lower levels of C3 than female PD patients [0.87 (0.22) vs. 1.02 (0.23), Pc < 0.01]. Patients suffering from attention/memory problems had significantly lower levels of IgA and C3 than those without these problems [1.92 (1.21) vs. 2.57 (0.76); 0.89 (0.24) vs. 0.97 (0.24), respectively, Pc < 0.04]. In addition, serum IgG levels were negatively associated with mood/cognition problem scores and were positively associated with gastrointestinal tract problem scores (adjusted R 2 = 0.063, F = 1.805, p = 0.038). Serum C3 levels were negatively associated with being male, age, and sleep/fatigue problem scores (adjusted R 2 = 0.123, F = 2.678, p = 0.001). CONCLUSION: The peripheral humoral immune response might be correlated with the non-motor symptoms of PD.

Change of intestinal microbiota in cerebral ischemic stroke patients.

BACKGROUND: Gut microbiota has been suggested to play a role in stroke patients. Nevertheless, little is known about gut microbiota and the clinical indexes in stroke patients. METHODS: Total of 30 cerebral ischemic stroke (CI) patients and 30 healthy control were enrolled in this study and the fecal gut microbiota was profiled via Illumina sequencing of the 16S rRNA V1-V2. The National Institutes of Health Stroke Scale (NIHSS) were used to quantify stroke severity and modified Rankin scale (mRS) to assess outcome for CI patients. The correlations between the clinical indexes and microbiota were evaluated. RESULTS: Though the microbial α-diversity and structure is similar between CI patients and healthy controls, the gut microbiota of CI patients had more short chain fatty acids producer including Odoribacter, Akkermansia, Ruminococcaceae_UCG_005 and Victivallis. We also found that the special microbes were correlation with serum index, such as norank_O_ _Mollicutes_RF9, Enterobacter, Ruminococcaceae_UCG-002 were negative correlation with LDL (r = - 0.401, P < 0.01), HDL (r = - 0.425, P < 0.01) and blood glucose (r = - 0.439, P < 0.001), while the HDL was significantly positive correlation with the genus Ruminococcus_1 (r = 0.443, P < 0.001). The Christensenellaceae_R-7_group and norank_f_Ruminococcaceae was significantly positive correlation with NIHSS1M (r = 0.514, P < 0.05; r = 0.449, P < 0.05) and mRS (r = 0.471, P < 0.05, r = 0.503, P < 0.01), respectively. On the other hand, the genus Enterobacter was significantly negative correlation with NIHSS1M (r = 0.449, P < 0.05) and mRS (r = 0.503, P < 0.01). CONCLUSIONS: This study suggests that CI patients showed significant dysbiosis of the gut microbiota with enriched short chain fatty acids producer, including Odoribacter, Akkermansia. This dysbiosis was correlation with the outcomes and deserves further study.

Minocycline Protects against Rotenone-Induced Neurotoxicity Correlating with Upregulation of Nurr1 in a Parkinson's Disease Rat Model.

The aim of this study was to investigate the effect of minocycline in rats with rotenone-induced Parkinson's disease (PD). The open field test was performed to determine the motor ability of the rats. Double immunofluorescence staining was used to detect the expression of tyrosine hydroxylase (TH) and Nurr1 in the substantia nigra (SN) of rats. The relative protein levels of TH, Nurr1, and the total- and phosphorylated-cAMP-response element binding protein (CREB) were determined by western blot analysis. The production of reactive oxygen species (ROS) and nitric oxide (NO) was detected by commercial kits. After exposure to rotenone for 28 days, rats exhibited decreased ambulation and rearing frequency and prolonged immobility time with loss of TH positive neurons in the SN. The phosphorylation levels of CREB and Nurr1 expression decreased significantly accompanied with the release of ROS and NO. Minocycline alleviated the motor deficits of rats lesioned by rotenone and elevated the expression of TH, as well as suppressing the release of ROS and NO in the SN. That was in line with the elevated phosphorylation levels of CREB and Nurr1 expression. In conclusion, our present study showed minocycline protected against neurotoxicity in a rotenone-induced rat model of PD, which was correlated with upregulation of Nurr1.