The impact of serum magnesium and calcium on the risk of epilepsy: A mendelian randomization study.

AIMS: To investigate the causal role of serum magnesium and calcium in epilepsy or any of its subtypes through Mendelian randomization (MR) approach. METHODS: Single nucleotide polymorphisms (SNPs) associated with serum magnesium and calcium were used as the instrumental variables. MR analyses were performed using the summary-level data for epilepsy extracted from International League Against Epilepsy Consortium (15,212 cases and 29,677 controls) to obtain the causal estimates. The analyses were replicated using FinnGen data (7224 epilepsy cases and 208,845 controls), and a meta-analysis was then conducted. RESULTS: The result of combined analyses showed that higher serum magnesium concentrations was associated with a reduced risk of overall epilepsy (odds ratios [OR] = 0.28, 95% confidence interval [CI], 0.12-0.62, p = 0.002). In ILAE, higher serum magnesium was suggestively associated with reduced risks of focal epilepsy (OR = 0.25, 95% CI 0.10-0.62, p = 0.003). However, the results cannot be repeated in sensitivity analyses. As for serum calcium, the results did not reach statistical significance with overall epilepsy (OR = 0.60, 95% CI, 0.31-1.17, p = 0.134). However, genetically predicted serum calcium concentrations showed an inverse association with risk of generalized epilepsy (OR = 0.35, 95% CI, 0.17-0.74, p = 0.006). CONCLUSION: The current MR analysis did not support a causal relationship between serum magnesium and epilepsy, but showed a causally negative association between genetically determined serum calcium and generalized epilepsy.

Sex differences in the relationship of serum creatinine to cystatin C ratio and depressive symptoms among middle-aged and older adults in China.

BACKGROUND: Sarcopenia is reported to be associated with depression. Recently, serum creatinine to cystatin C ratio (CCR) has been recommended as a promising biomarker for detecting sarcopenia. The purpose of this study was to explore the relationship between CCR and depressive symptoms among middle-aged and older adults using the baseline data of the China Health and Retirement Longitudinal Study (CHARLS). METHODS: This study included 7083 participants aged 45 and older. A score of 10-item Center for Epidemiological Studies Depression Scale (CESD-10) ≥ 12 was used as the cut-off of having depressive symptoms. CCR was calculated by serum creatinine (mg/dL)/cystatin C (mg/L). The t-test and Chi-squared test were applied to compare the differences between the depressive symptoms group and no depressive symptoms group in both sexes. Unadjusted and adjust logistic regression models were used to further investigate the relationship between CCR and depressive symptoms. RESULTS: In the fully adjusted logistic regression models, higher CCR was significantly correlated with a lower incidence of depressive symptoms in males (OR = 0.486, P = 0.001, 95 % CI = 0.314-0.752), but not in females (OR = 0.775 P = 0.184, 95 % CI = 0.532-1.129). LIMITATIONS: 1. Self-reported method was used to define depressive symptoms by CESD-10; 2. History of chronic diseases were all self-reported; 3. Residual bias was still possible after controlling for many confounding factors. CONCLUSIONS: Lower CCR was significantly correlated with increased depressive symptoms in males, but not in females. More studies are needed to further confirm this conclusion.

Serum creatinine to cystatin C ratio and cognitive function among middle-aged and older adults in China.

Background: The sarcopenia index (SI, serum creatinine/serum cystatin C × 100) is recently suggested to be a reliable marker for sarcopenia. It has been reported that sarcopenia is associated with poorer cognition. The purpose of this study was to evaluate the correlation between SI and cognitive function among middle-aged and older adults from the China Health and Retirement Longitudinal Study (CHARLS). Materials and methods: A total of 6,442 participants ≥45 years of age were enrolled in this study from CHARLS between 2011 and 2012. Cognitive function was assessed by interview-based measurements, including orientation and attention, episodic memory, visuo-construction, and the total cognitive function. SI was calculated by serum creatinine (mg/dL)/cystatin C (mg/L) × 100. One-way analysis of variance (ANOVA) was used to compare the differences among groups divided according to SI quartiles by gender. Both linear and logistic regression models were applied to investigate the relationship between SI and cognitive function. Results: After adjustment for potential confounders, we found SI was significantly and positively correlated with total cognitive function scores both in males and females [ß = 0.014, 95% confidence interval (CI) 0.007 to 0.021, P < 0.001; ß = 0.011, 95 CI% 0.003 to 0.018, P = 0.004; respectively]. Similarly, when the total cognitive function score was treated as a categorical variable according to quartiles in males and females, higher SI was related to better total cognitive function scores in both males and females [odds ratio (OR) = 1.147, 95% CI 1.028 to 1.279, P = 0.014; OR = 1.219, 95% CI 1.106 to 1.344, P < 0.001; respectively] following adjustment for confounders. Conclusions: Lower sarcopenia index was correlated with a higher prevalence of cognitive impairment among middle-aged and older adults in China.

Prognostic value of sarcopenia in patients with rectal cancer: A meta-analysis.

BACKGROUND: Sarcopenia is usually characterized by the loss of skeletal muscle mass and impaired muscle function which is commonly seen in the elderly. It has been found to be associated with poorer prognoses in many types of cancer. Computed tomography (CT) scan is frequently used to assess skeletal muscle mass and further calculate skeletal muscle index (SMI) at the third lumbar vertebra level (L3), which is used to define sarcopenia. The purpose of this meta-analysis was to assess the prognostic value of sarcopenia for overall survival (OS) in patients with rectal cancer. METHODS: We performed a systematic search to find relevant studies published up to 14 January 2021 in PubMed, Embase, Web of science and Scopus. In our meta-analysis, studies comparing OS in rectal cancer patients with sarcopenia versus those without were included. Quality assessment for included studies was evaluated according to the Quality in Prognosis Studies (QUIPS) tool. We directly extracted hazard ratios (HRs) with 95% confidence intervals (CIs) in both univariate and multivariate analyses from each study. The Cochrane Collaboration's Review Manager 5.4 software was applied to analyze data. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidelines and website GRADEpro. RESULTS: Finally, a total of 7 studies involving 2377 patients were included. The pooled HRs were 2.10 (95% CI 1.33-3.32, P = 0.001) and 2.37 (95% CI 1.13-4.98, P = 0.02) using random-effects models in univariate and multivariate analyses, respectively. The results showed a significant association between sarcopenia and OS in patients with rectal cancer. The quality of the evidence for OS was moderate for both univariate and multivariate analyses. CONCLUSION: CT-defined sarcopenia is an independent predictor for worse OS in patients with rectal cancer. Future studies with a more stringent definition of sarcopenia are required to further confirm our findings.

Improving the Quality of Emergency Intrahospital Transport for Critically Ill Patients by Using Toyota Production System Methods.

Objective: To explore the effects of the Toyota Production System (TPS) for improving the quality of emergency intrahospital transport for critically ill patients in management. Methods: Between April and June 2021, 68 critically ill patients were transported to corresponding wards, while 63 critically ill patients were transported to corresponding wards between July and September 2021. The pre-TPS and post-TPS management groups each included 30 cases based on their propensity score. The TPS management tool was combined with the PDCA method for analysing the current situation as well as determining the target for improvement, calculating the value and process efficiencies, and modifying and evaluating relevant processes. At last, the changes in transport time, receiving department, patient satisfaction, and adverse event rate of critically ill patients after TPS management were analysed. Results: The total intrahospital transport time of critically ill patients decreased from 39 minutes (median) before the implementation of TPS management to 27 minutes (median) after TPS management, and the difference was statistically significant (P<0.05). Process efficiency and value efficiency both increased from 33.33% and 38.46% before TPS management to 42.86% and 40.74% after TPS management, respectively. Likewise, the satisfaction of receiving departments and patients increased from 73.33% and 76.67% before TPS management to 96.67% and 96.67% after TPS management (P<0.001). Finally, the adverse event rate decreased as a result of TPS management from 13.33% to 3.33% (P>0.05). Conclusion: TPS management may significantly shorten the intrahospital transport time for critically ill patients, reduce the occurrence of adverse events in emergency care, advance patient satisfaction, and improve the overall quality and safety of emergency care.

Pan-Cancer Analysis of Microfibrillar-Associated Protein 2 (MFAP2) Based on Bioinformatics and qPCR Verification.

MFAP2 has been reported to play an oncogenic role in several types of human cancers. However, the expression profile of MFAP2 in various cancers and its impact on prognosis and immune infiltration remain unclear. In this study, the mRNA expression and protein expression of MFAP2 in normal tissues, tumor cell lines, and 33 malignant tumor tissues were analyzed comprehensively using Genotype-Tissue Expression (GTEx), Cancer Cell Line Encyclopedia (CCLE), and The Cancer Genome Atlas (TCGA), Oncomine and UALCAN databases, and the expression of MFAP2 in different grades and stages of cancers was assessed using Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and Tumor and Immune System Interaction Database (TISIDB). In general, MFAP2 showed distinct expression in most tumor and normal tissues, closely associated with higher tumor grade, higher tumor stage, and poor survival in multiple cancers. A search of the UALCAN database and the cBioPortal database revealed that this difference in mRNA level expression could be partly attributed to abnormal DNA methylation and mutations at the genomic level. In addition, MFAP2 expression was also associated with tumor mutation burden, microsatellite instability, and neoantigens in different cancer types. More importantly, the TIMER and TISIDB databases also showed that MFAP2 levels were significantly correlated with immune infiltration abundance and immune-related gene markers, as well as ESTIMATE scores. By qPCR, MFAP2 expression was validated in four kinds of tumor tissue samples. The present study combined several databases and performed a pan-cancer analysis of the expression profile, methylation, and mutation for MFAP2 and its implications for prognosis and immune infiltration, suggesting that MFAP2 could contribute to malignant properties of many tumors. MFAP2 may be an important biomarker with prognostic value and has the potential to be a target for tumor immunotherapy.

Association of CSF GAP-43 and APOE ε4 with Cognition in Mild Cognitive Impairment and Alzheimer's Disease.

The growth-associated protein 43 (GAP-43) is a presynaptic phosphoprotein in cerebrospinal fluid (CSF). The ε4 allele of apolipoprotein E (APOE) is an important genetic risk factor for Alzheimer's disease (AD). We aimed to evaluate the association of CSF GAP-43 with cognition and whether this correlation was related to the APOE ε4 status. We recruited participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, and they were divided into cognitively normal (CN) ε4 negative (CN ε4-), CN ε4 positive (CN ε4+), mild cognitive impairment (MCI) ε4 negative (MCI ε4-), MCI ε4 positive (MCI ε4+), AD ε4 negative (AD ε4-), and AD ε4 positive (AD ε4+) groups. Spearman's correlation was utilized to evaluate the relationship between CSF GAP-43 and core AD biomarkers at the baseline. We performed receiver-operating characteristic (ROC) curve analyses to investigate the diagnostic accuracy of CSF GAP-43. The correlations between CSF GAP-43 and the Mini-Mental State Examination (MMSE) scores and brain atrophy at baseline were assessed by using multiple linear regression, while the association between CSF GAP-43 and MMSE scores at the follow-up was tested by performing the generalized estimating equation (GEE). The role of CSF GAP-43 in the conversion from MCI to AD was evaluated using the Cox proportional hazard model. We found that the CSF GAP-43 level was significantly increased in MCI ε4+, AD ε4- and AD ε4+ groups compared with CN ε4- or MCI ε4- group. The negative associations between the CSF GAP-43 and MMSE scores at the baseline and follow-up were found in MCI ε4- and MCI ε4+ groups. In addition, baseline CSF GAP-43 was able to predict the clinical progression from MCI to AD. CSF GAP-43 may be a promising biomarker to screen cognition for AD. The effects of CSF GAP-43 on cognition were suspected to be relevant to APOE ε4 status.

Peritumoral Edema Is Associated With Postoperative Hemorrhage and Reoperation Following Vestibular Schwannoma Surgery.

Background: Postoperative hemorrhage (POH) is a severe complication following vestibular schwannoma surgery that may require surgical treatment. The purpose of our study is to identify risk factors associated with POH and reoperation following the resection of vestibular schwannoma. Methods: We retrospectively recruited 452 vestibular schwannoma patients treated with retrosigmoid approach. The primary outcome was POH, and the secondary outcome was reoperation for POH. Clinical and radiographic data were compared by performing univariate analysis and logistic regression analysis. Results: Among the 452 patients, 37 patients (8.2%) presented with POH and14 patients (3.1%) required reoperation within a 30-day hospitalization period. The univariate analysis showed that peritumoral edema, tumor diameter >30 mm, severe postoperative hypertension, and length of hospital stay were associated with POH and reoperation for POH. Logistic regression analysis showed that peritumoral edema [odds ratio (OR) 4.042, 95% confident interval (CI) 1.830-8.926, P = 0.001] and tumor diameter >30 mm (OR 3.192, 95% CI 1.421-7.168, P = 0.005) were independent predictive factors for POH. Peritumoral edema (OR 7.071, 95% CI 2.342-21.356, P = 0.001) was an independent predictive factor for reoperation by using logistic regression analysis. Further analysis revealed that larger tumor and incomplete tumor resection were both associated with a higher incidence of peritumoral edema. Conclusion: Peritumoral edema and tumor size are independent risk factors for POH following vestibular schwannoma surgery. And larger hematoma occurs more commonly in tumors with peritumoral edema which may require reoperation. Tumor size and extent of tumor resection are associated with peritumoral edema. Close attention should be paid to high-risk patients especially for those who presented with severe postoperative hypertension.

Diagnostic accuracy assessment of molecular prediction model for the risk of NAFLD based on MRI-PDFF diagnosed Chinese Han population.

BACKGROUND: Several molecular prediction models based on the clinical parameters had been constructed to predict and diagnosis the risk of NAFLD, but the accuracy of these molecular prediction models remains need to be verified based on the most accurate NAFLD diagnostic method. The aim of this study was to verify the accuracy of three molecular prediction models Fatty liver index (FLI), NAFLD liver fat score system (NAFLD LFS), and Liver fat (%) in the prediction and diagnosis of NAFLD in MRI-PDFF diagnosed Chinese Han population. PATIENTS AND METHODS: MRI-PDFF was used to diagnose the hepatic steatosis of all the subjects. Information such as name, age, lifestyle, and major medical histories were collected and the clinical parameters were measured by the standard clinical laboratory techniques. The cut-off values of each model for the risk of NAFLD were calculated based on the MRI-PDFF results. All data were analyzed using the statistical analysis software SPSS 23.0. RESULTS: A total of 169 subjects were recruited with the matched sex and age. The ROC curves of FLI, NAFLD LFS, and Liver fat (%) models were plotted based on the results of MRI-PDFF. We founded that the accuracy of FLI, NAFLD LFS, and Liver fat (%) models for the prediction and diagnosis of NAFLD were comparative available in Chinese Han population as well as the validity of them in other ethnics and regions. CONCLUSIONS: The molecular prediction models FLI, NAFLD LFS, and Liver fat (%) were comparative available for the prediction and diagnosis of NAFLD in Chinese Han population. MRI-PDFF could be used as the golden standard to develop the new molecular prediction models for the prediction and diagnosis of NAFLD.

Metformin attenuates plaque-associated tau pathology and reduces amyloid-ß burden in APP/PS1 mice.

BACKGROUND: The neuropathological hallmarks of Alzheimer's disease (AD) are amyloid-ß (Aß) plaques and neurofibrillary tangles (NFTs). The amyloid cascade theory is the leading hypothesis of AD pathology. Aß deposition precedes the aggregation of tau pathology and Aß pathology precipitates tau pathology. Evidence also indicates the reciprocal interactions between amyloid and tau pathology. However, the detailed relationship between amyloid and tau pathology in AD remains elusive. Metformin might have a positive effect on cognitive impairments. However, whether metformin can reduce AD-related pathologies is still unconclusive. METHODS: Brain extracts containing tau aggregates were unilaterally injected into the hippocampus and the overlying cerebral cortex of 9-month-old APPswe/PS1DE9 (APP/PS1) mice and age-matched wild-type (WT) mice. Metformin was administrated in the drinking water for 2 months. Aß pathology, tau pathology, plaque-associated microgliosis, and autophagy marker were analyzed by immunohistochemical staining and immunofluorescence analysis 2 months after injection of proteopathic tau seeds. The effects of metformin on both pathologies were explored. RESULTS: We observed tau aggregates in dystrophic neurites surrounding Aß plaques (NP tau) in the bilateral hippocampi and cortices of tau-injected APP/PS1 mice but not WT mice. Aß plaques promoted the aggregation of NP tau pathology. Injection of proteopathic tau seeds exacerbated Aß deposits and decreased the number of microglia around Aß plaques in the hippocampus and cortex of APP/PS1 mice. Metformin ameliorated the microglial autophagy impairment, increased the number of microglia around Aß plaques, promoted the phagocytosis of NP tau, and reduced Aß load and NP tau pathology in APP/PS1 mice. CONCLUSION: These findings indicate the existence of the crosstalk between amyloid and NP tau pathology. Metformin promoted the phagocytosis of pathological Aß and tau proteins by enhancing microglial autophagy capability. It reduced Aß deposits and limited the spreading of NP tau pathology in APP/PS1 mice, which exerts a beneficial effect on both pathologies.

Interferon Regulatory Factor 5 Mediates Lipopolysaccharide-Induced Neuroinflammation.

Background: Activated microglia play a vital role in neuroinflammation in the central nervous system (CNS), which is associated with the pathogenesis and the progression of neurological diseases. Interferon regulatory factor 5 (IRF5) has been well established participating in inflammatory responses and is highly expressed in M1 macrophage in the periphery, the role of which in the CNS remains elusive. Methods: Lipopolysaccharide (LPS) was employed to induce neuroinflammation. Down-regulation of IRF5 in C57/BL6 mice and BV2 microglial cells were achieved by IRF5 siRNA transfection. The levels of pro-inflammatory cytokines were evaluated by ELISA and quantitative real-time PCR. The expression levels of IRF5 were examined by immunofluorescence and Western blot. Results: LPS induced significantly elevated expression of IRF5 in mouse brain, which co-localized with CD11b-positive microglia. Down-regulation of IRF5 quenched the pro-inflammatory responses. The levels of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6 were up-regulated at 4 h after LPS treatment, which were significantly down-regulated with the knockdown of IRF5. LPS-induced pro-inflammatory responses were transient, which were comparable to control group at 24 h after LPS treatment. However, LPS did not up-regulate the expression of IRF5 in BV2 microglial cells, indicating that LPS-induced inflammation in BV2 cells does not involve IRF5 signaling. Conclusions: IRF5 mediates the inflammatory responses in the CNS, which might serve as a therapeutic target for CNS inflammatory diseases. LPS-induced inflammation does not involve IRF5 signaling in BV2 microglia.

The differential effects of isoflurane and sevoflurane on neonatal mice.

Previous research has shown that exposure to volatile anesthetics can induce acute neuroinflammation and neuroapoptopsis in neonatal rodents and that these events can lead to cognitive dysfunction at later stages. Isoflurane and sevoflurane are two of the most popular anesthetics used in the field of pediatrics. However, the relative impact of these two anesthetics on the developing brain at distinct time points after the induction of anesthesia has not been compared. In the present study, we exposed 7-day-old mice to clinically equivalent doses of isoflurane (1.5%) and sevoflurane (2.5%) for 4 h and then investigated consequential changes in the brains of these mice at six different time points. We analyzed the levels of proteins that are directly related to neuroapoptosis, neuroinflammation, synaptic function, and memory, in the brains of neonatal mice. Exposure of neonatal mice to isoflurane and sevoflurane resulted in acute neuronal apoptosis. Our analysis observed significant levels of neuroinflammation and changes in the expression levels of proteins associated with both synaptic transmission and memory in mice from the isoflurane group but not the sevoflurane group. Our results therefore indicate that isoflurane and sevoflurane induce differential effects in the brains of neonatal mice.

Evaluation of the Mini-Mental State Examination and the Montreal Cognitive Assessment for Predicting Post-stroke Cognitive Impairment During the Acute Phase in Chinese Minor Stroke Patients.

Objective: To assess the value of the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) during acute phase in predicting post-stroke cognitive impairment (PSCI) at 3-6 months. Methods: We prospectively recruited 229 patients who had suffered their first-ever ischemic stroke. PSCI was determined in 104 of these patients by a comprehensive neuropsychological battery performed at 3-6 months. Receiver operating characteristic (ROC) curve analysis was then performed to compare the discriminatory ability of the MMSE and MoCA. Also, we applied a decision tree generated by the classification and regression tree methodology. Results: In total, 66 patients had PSCI when evaluated 3-6 months after the onset of minor stroke. Logistic regression analysis revealed that education, body mass index (BMI), and baseline MoCA scores were independently associated with PSCI. ROC curve analysis showed that the ability to predict PSCI was similar when compared between baseline MoCA scores [area under curve (AUC), 0.821; 95% confidence interval (CI), 0.743-0.898] and baseline MMSE scores (AUC, 0.809; 95% CI, 0.725-0.892, P = 0.75). Both MMSE and MoCA exhibited similar predictive values at their optimal cut-off points (MMSE ≤27; sensitivity, 0.682; specificity, 0.816; MoCA ≤21; sensitivity, 0.636; specificity, 0.895). Classification and regression tree-derived analysis yielded an AUC of 0.823 (sensitivity, 0.803; specificity, 0.842). Conclusion: When applied within 2 weeks of stroke, the MMSE and MoCA are both useful and have similar predictive value for PSCI 3-6 months after the onset of minor stroke.

Efficacy and Safety of Intraoperative Lumbar Drain in Endoscopic Skull Base Tumor Resection: A Meta-Analysis.

Objectives: This study aims to evaluate the efficacy and safety of lumbar drainage (LD) in preventing cerebrospinal fluid (CSF) leaks after endoscopic skull base tumor resection. Methods: A systematic online search was conducted using PubMed, Embase, Scopus, Web of Science, and Cochrane Library from January 2006 to July 2019. Data analyses were performed by the Cochrane Collaboration's Review Manager 5.3 software. Results: Eight studies, including two randomized controlled trials and six observational studies, met the inclusion criteria. No significant difference was found in the post-operative CSF leak rate between the LD group and the non-LD group [odds ratio (OR), 0.80; 95%CI, 0.37-1.74; I 2 = 37%; P = 0.57). Subgroup analysis of the intraoperative high-flow leaks, including 4 studies and 313 patients, showed that LD was associated with reduced likelihood of post-operative CSF leak (OR, 0.37; 95%CI, 0.17-0.83; I 2 = 0%; P = 0.02). The placement of LD was related to increased risk of headache compared with non-LD use, and no significant difference was found in the occurrence of deep vein thromboses and pulmonary emboli between two groups. Conclusion: LD is not recommended in all patients undergoing endoscopic skull base tumor resection. However, for patients with intraoperative high-flow leaks, LD is effective and safe in reducing risk of CSF leak.

Altered Expression Profile of Phosphatidylinositols in Erythrocytes of Alzheimer's Disease and Amnestic Mild Cognitive Impairment Patients.

BACKGROUND: Studies have demonstrated that the levels of phospholipids, including phosphatidylinositols (PIs), were decreased in Alzheimer's disease (AD) brain, presenting as a potential biomarker for AD. The plasma phospholipids levels have also been discovered to predict the conversion of cognitively normal elderly adults to amnestic mild cognitive impairment (aMCI) or demented patients. OBJECTIVE: To investigate the expression profile of PIs in erythrocytes of AD and aMCI patients, which would serve as a blood-based method to distinguish AD and aMCI patients from normal controls (NC). METHODS: In this study, we used anion-exchange high-performance liquid chromatography to analyze PIs alterations in erythrocytes from a total of 86 prospectively recruited subjects (including 24 NC, 21 aMCI patients, and 41 AD patients). RESULTS: We found that the levels of PI40 : 4, PI3/5P, and PI(3,4)P2 in aMCI patients, and the levels of PI4P, PI(3,4)P2, and PI3/5P in AD patients were significantly decreased compared to NC. The changed expression profile of PIs could effectively discriminate AD and aMCI patients from NC (AUC = 0.964, 0.938, respectively). CONCLUSION: The altered expression profile of erythrocytes PIs might be a potential blood-based biomarker for AD and aMCI. This alteration of PIs probably reflected the impaired deformability and oxygen-carrying capacity of erythrocytes in AD and aMCI patients.

Decreased risk of Parkinson's disease in diabetic patients with thiazolidinediones therapy: An exploratory meta-analysis.

BACKGROUND: It has been found that thiazolidinediones (TZDs) may play a protective role in animal models of Parkinson's disease (PD), while the results remain controversial whether TZDs protect against Parkinson's disease in humans. The purpose of this meta-analysis is to explore the association between TZDs use and the incidence of PD in diabetic patients. METHODS: A systematic online search was conducted to find studies published up to 31 December 2018. In our exploratory meta-analysis, studies comparing incidence of PD between TZD-treated and non-TZD-treated groups of diabetic patients were included. Data analysis was performed using a random or fixed effects model and expressed as odds ratios (OR) with 95% confidence interval (95% CI). We used the Cochrane Collaboration's Review Manager 5.3 software to analyze data. RESULTS: In total, 5 retrospective observational cohort studies were identified which met the inclusion criteria. The pooled odds ratio (OR) was 0.70 [95% CI, 0.51 to 0.96; p = 0.03] in a random-effects model, indicating a 30% lower risk of developing PD in diabetic patients treated with TZDs compared with non-TZD-treated patients. CONCLUSION: In this exploratory meta-analysis, we found that TZDs use was associated with reduced risk of PD in diabetic patients. However, this meta-analysis was not registered online although we followed a protocol designed for it. Further prospective observational studies with larger sample size and more strict inclusion criteria including controlling for diabetes complication severity index, hypoglycemic drugs combination, sex ratio, and comorbidity are needed to guide whether RCTs are warranted. And RCTs can better determine whether TZDs use could lower incidence of PD in diabetic patients.

Cerebral sparganosis presenting with atypical postcontrast magnetic resonance imaging findings: a case report and literature review.

BACKGROUND: Sparganosis, a rare and severe parasitic infection caused by the larvae of Spirometra species or simply sparganum, generally involves subcutaneous tissue or muscle. But occasionally, sparganum can also invade the human brain, resulting in cerebral sparganosis. CASE PRESENTATION: A 33-year-old woman presented with a 10-day history of headache. Postcontrast magnetic resonance imaging (MRI) revealed an irregular lesion with enhancement and the tunnel-shaped focus extending to the contralateral hemiphere. Cerebrospinal fluid (CSF) analysis disclosed pleocytosis (166 cells/µL) and an elevated protein concentration (0.742 g/L). Enzyme-linked immunosorbent assay (ELISA) revealed positive sparganum-specific antibody in both blood and CSF. Finally, the diagnosis of cerebral sparganosis was comfirmed. She received praziquantel treatment and got a favorable outcome during six-month follow-up. CONCLUSIONS: Irregular enhancement and the tunnel sign that extends to the contralateral hemisphere on postconstrast MRI are unusual presentations of cerebral sparganosis. ELISA for sparganum-specific antibody can help confirm the diagnosis. Although surgery is the preferred treatment for cerebral sparganosis, praziquantel might also achieve satisfying outcomes.

Microbiota-gut-brain axis and toll-like receptors in Alzheimer's disease.

Alzheimer's disease (AD) is a multifactorial disease which involves both the periphery and central nervous system (CNS). It has been recently recognized that gut microbiota interacts with the gut and brain (microbiota-gut-brain axis), contributing to the pathogenesis of neurodegenerative diseases, such as AD. Dysbiosis of gut microbiota can induce increased intestinal permeability and systemic inflammation, which may lead to the development of AD pathologies and cognitive impairment via the neural, immune, endocrine, and metabolic pathways. Toll-like receptors (TLRs) play an important role in the innate immune system via recognizing microbes-derived pathogens and initiating the inflammatory process. TLRs have also been found in the brain, especially in the microglia, and have been indicated in the development of AD. In this review, we summarized the relationship between microbiota-gut-brain axis and AD, as well as the complex role of TLRs in AD. Intervention of the gut microbiota or modulation of TLRs properly might emerge as promising preventive and therapeutic strategies for AD.