Free Water MR Imaging of White Matter Microstructural Changes is a Sensitive Marker of Amyloid Positivity in Alzheimer's Disease.

BACKGROUND: Extracellular free water (FW) resulting from white matter degeneration limits the sensitivity of diffusion tensor imaging (DTI) in predicting Alzheimer's disease (AD). PURPOSE: To evaluate the sensitivity of FW-DTI in detecting white matter microstructural changes in AD. To validate the effectiveness of FW-DTI indices to predict amyloid-beta (Aß) positivity in mild cognitive impairment (MCI) subtypes. STUDY TYPE: Retrospective. POPULATION: Thirty-eight Aß-negative cognitively healthy (CH) controls (68.74 ± 8.28 years old, 55% female), 15 Aß-negative MCI patients (MCI-n) (68.87 ± 8.83 years old, 60% female), 29 Aß-positive MCI patients (MCI-p) (73.03 ± 7.05 years old, 52% female), and 29 Aß-positive AD patients (72.93 ± 9.11 years old, 55% female). FIELD STRENGTH/SEQUENCE: 3.0T; DTI, T1 -weighted, T2 -weighted, T2 star-weighted angiography, and Aß PET (18 F-florbetaben or 11 C-PIB). ASSESSMENT: FW-corrected and standard diffusion indices were analyzed using trace-based spatial statistics. Area under the curve (AUC) in distinguishing MCI subtypes were compared using support vector machine (SVM). STATISTICAL TESTS: Chi-squared test, one-way analysis of covariance, general linear regression analyses, nonparametric permutation tests, partial Pearson's correlation, receiver operating characteristic curve analysis, and linear SVM. A P value <0.05 was considered statistically significant. RESULTS: Compared with CH/MCI-n/MCI-p, AD showed significant change in tissue compartment indices of FW-DTI. No difference was found in the FW index among pair-wise group comparisons (the minimum FWE-corrected P = 0.114). There was a significant association between FW-DTI indices and memory and visuospatial function. The SVM classifier with tissue radial diffusivity as an input feature had the best classification performance of MCI subtypes (AUC = 0.91), and the classifying accuracy of FW-DTI was all over 89.89%. DATA CONCLUSION: FW-DTI indices prove to be potential biomarkers of AD. The classification of MCI subtypes based on SVM and FW-DTI indices has good accuracy and could help early diagnosis. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Artificial photosynthesis systems for solar energy conversion and storage: platforms and their realities.

In natural photosynthesis, photosynthetic organisms such as green plants realize efficient solar energy conversion and storage by integrating photosynthetic components on the thylakoid membrane of chloroplasts. Inspired by natural photosynthesis, researchers have developed many artificial photosynthesis systems (APS's) that integrate various photocatalysts and biocatalysts to convert and store solar energy in the fields of resource, environment, food, and energy. To improve the system efficiency and reduce the operation cost, reaction platforms are introduced in APS's since they allow for great stability and continuous processing. A systematic understanding of how a reaction platform affects the performance of artificial photosynthesis is conducive for designing an APS with superb solar energy utilization. In this review, we discuss the recent APS's researches, especially those confined on/in platforms. The importance of different platforms and their influences on APS's performance are emphasized. Generally, confined platforms can enhance the stability and repeatability of both photocatalysts and biocatalysts in APS's as well as improve the photosynthetic performance due to the proximity effect. For functional platforms that can participate in the artificial photosynthesis reactions as active parts, a high integration of APS's components on/in these platforms can lead to efficient electron transfer, enhanced light-harvesting, or synergistic catalysis, resulting in superior photosynthesis performance. Therefore, the integration of APS's components is beneficial for the transfer of substrates and photoexcited electrons in artificial photosynthesis. We finally summarize the current challenges of APS's development and further efforts on the improvement of APS's.

Zishen pingchan granules combined with pramipexole in the improvement of depressive symptoms in Parkinson's disease: a prospective, multicenter, randomized, double-blind, controlled clinical study.

BACKGROUND AND OBJECTIVE: Zishen Pingchan granule (ZPG), a traditional Chinese herbal recipe for treating Parkinson's disease (PD), is usually used as an add-on drug with some antiparkinsonian drugs in China. The objectives of this study were to evaluate the efficacy, safety, and tolerability of ZPG combined with pramipexole in the treatment of depression in PD (dPD). METHODS: A 12-week, multicenter, randomized, double-blind, and placebo-controlled study on ZPG was performed on a total of 200 patients who were treated with pramipexole but still had mild to moderate depressive symptoms. Patients were randomly divided into ZPG (n = 100) or placebo (n = 100). The primary effective result was the mean change from the baseline on the Hamilton Depression Scale 17 items (HAM-D-17) over 12 weeks and the clinical efficacy rate. Secondary endpoints were the mean change from the baseline in the Geriatric Depression Scale (GDS-15), Unified Parkinson's disease rating scale Part III (UPDRS III), Parkinson's quality of life scale (PDQ-8), and Parkinson's disease sleep scale (PDSS-2) over 12 weeks. RESULTS: After 12 weeks of treatment, ZPG significantly reduced the mean [95% confidence interval] HAMD score vs. placebo (- 1.43 scores [- 2.50, - 0.36]; p = 0.009). The clinical remission rate and responders of the ZPG group were higher than those of the placebo (46.1% vs. 31.0%; p = 0.041; 34.8% vs. 18.4%; p = 0.014). A significant improvement in the PDSS-2 score was also observed in the ZPG group compared with that in the placebo group (- 3.56 scores [- 5.77, - 1.35]; p = 0.002). A total of 7 patients (7.1%) in the ZPG group had mild adverse events (AEs) vs 9 patients (9%) in the placebo group. No severe AEs were observed in either group. The randomization and controlled clinical study revealed that ZPG was effective, safe, and well-tolerated. CONCLUSION: ZPG combined with pramipexole further reduced the depressive symptoms and improved the sleeping quality of PD patients. Trial registration The protocol was retrospectively registered at the Chinese Clinical Trial Registry, Unique identifier: ChiCTR1800019942, date of registration: December 9, 2018; http://www.chictr.org.cn/showproj.aspx?proj=30432.

Early implementation of intended exercise improves quality of life in Parkinson's disease patients.

OBJECTIVE: Recent data have shown that regular exercise may ameliorate motor symptoms in Parkinson's disease (PD). This study aims to investigate how intended exercise impacts motor and non-movement symptoms of PD. METHODS: Eighty-eight patients were randomly assigned to an early exercise group (E-EG), late exercise group (L-EG), or a control group (CG) using a randomized delayed-start design. The E-EG carried out a rigorous, formal exercise program for 1 h, twice per week, for 18 months (May 2018-November 2019). The L-EG took part in the exercise program in the final 6-12 months of the study. We assessed outcomes using the Unified Parkinson's Disease Rating Scale (UPDRS), PDQ-39 Questionnaire, Line A test, Line B test, Nine-hole column test, 30 s squat and stand-up test (30 s SST), 10-m walk test (10mW), Balance Evaluation Systems Mini Test (MiniBESTest), FAB, and Time Up and Go Test (TUG). RESULTS: The patients with PD in the E-EG had lower performance in the UPDRS and Line B test compared to those in the L-EG at post-exercise (p < 0.05). Moreover, the patients with PD in the E-EG had much lower performance in the PDQ-39 and 9-Hole Peg test compared to those in the L-EG at post-exercise (p < 0.01). CONCLUSION: Implementation of an exercise regimen improved the movement abilities and quality of life in PD patients, especially in the E-EG. This data supports the idea that intended exercise should be implemented as part of the treatment strategy for PD patients as early as possible.

Dyskinesia-hyperpyrexia syndrome in Parkinson's disease: a systematic review.

PURPOSE: Dyskinesia-hyperpyrexia syndrome (DHS) is a rare but life-threatening disease. The clinical manifestations of this syndrome overlap substantially with Parkinson hyperpyrexia syndrome and serotonin syndrome and are often confused by clinicians. The purpose of this review was to enable clinicians to recognize this syndrome and thereby reach a correct diagnosis and provide optimal treatments to improve prognosis in clinical practice. METHODS: Using the methodology described in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we conducted a literature search of the PubMed, Embase, and MEDLINE databases using keywords in titles and abstracts of published literature. Quality assessment was performed using the modified Newcastle-Ottawa scale. RESULTS: A total of 11 patients obtained from nine publications were included in this systematic review. All of the cases occurred in patients with advanced Parkinson's disease (PD) of long disease duration. High ambient temperature was the most common trigger of this syndrome. Hyperpyrexia and dyskinesias were present in all cases. The consciousness disturbances of this syndrome included confusion, hallucination, and lethargy or stupor. Autonomic dysfunction (except for hyperpyrexia) is uncommon in DHS, and only two patients presented with tachycardia. The treatment of this syndrome included supportive interventions (including rehydration, anti-pyretic and anti-infection treatments, and maintaining electrolyte balance), dopaminergic drug reduction and sedation. Two patients died due to DHS. CONCLUSIONS: We summarized the triggers, clinical features, and treatments of all reported dyskinesia-hyperpyrexia syndrome cases, proposed guiding diagnostic criteria, and established a flow chart to guide diagnoses to quickly identify these three syndromes in clinical practice.

Structural and Functional Thalamic Changes in Parkinson's Disease With Mild Cognitive Impairment.

BACKGROUND: The thalamus is a key node of deep gray matter and previous studies have demonstrated that it is involved in the modulation of cognition. PURPOSE: To investigate the volume changes of the thalamus and its subregions and altered thalamus functional connectivity patterns in Parkinson's disease (PD) patients with and without mild cognitive impairment (MCI). STUDY TYPE: Prospective. POPULATION: Thirty-three patients with MCI (PD-MCI), 36 PD patients having no cognitive impairment (PD-NCI), 21 healthy controls (HCs). SEQUENCE: 3.0T MRI scanner; 3D T1 -weighted fast spoiled gradient recalled echo (3D T1 -FSPGR); resting-state fMRI ASSESSMENT: Voxel-based morphometry (VBM) was performed to calculate the volume of the thalamus and its subregions. The left and right total thalamus were considered seeds and seed-based functional connectivity (FC) was analyzed. Additionally, correlations between volumes and cognitive performance and between FC values and cognitive performance were examined separately. STATISTICAL TEST: Analysis of covariance (ANCOVA); two-sample t-tests; partial correlation analysis. RESULTS: The volumes of the total thalamus (PD-MCI vs. PD-NCI vs. HCs: 18.39 ± 1.67 vs. 19.63 ± 1.79 vs. 19.47 ± 1.35) and its subregions were significantly reduced in PD-MCI as compared to PD-NCI (total thalamus: P = 0.002) and HCs (total thalamus: P = 0.012). Compared with PD-NCI, PD-MCI showed increased FC between the thalamus and bilateral middle cingulate cortex and left posterior cingulate cortex, and decreased FC between thalamus and the left superior occipital gyrus, left cuneus, left precuneus, and left middle occipital gyrus. Volumes of thalamus and the subregions, as well as the FC of thalamus with the identified regions, were significantly correlated (P < 0.05, FDR-corrected) with neuropsychological scores in PD patients. DATA CONCLUSION: We noted volume loss and altered FC of thalamus in PD-MCI patients, and these changes were correlated with global cognitive performance. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICIENCY: Stage 2 J. Magn. Reson. Imaging 2020;52:1207-1215.

Alterations of regional homogeneity in Parkinson's disease with mild cognitive impairment: a preliminary resting-state fMRI study.

PURPOSE: Mild cognitive impairment (MCI) is commonly observed in Parkinson's disease (PD), even in the early stages. However, the neural substrates of cognitive impairment in PD remain unclear. The aim of the current study was to investigate the change of local brain function in PD patients with MCI. METHODS: Fifty patients with PD, including 25 PD patients with MCI (PD-MCI) and 25 PD patients with normal cognition (PD-NC), and 25 age- and sex-matched healthy controls (HC) were enrolled. Conventional magnetic resonance imaging (MRI), 3D structural images, and resting state-functional MRI (rs-fMRI) were performed in all subjects. Regional homogeneity (ReHo) was measured based on the rs-fMRI images to investigate the altered local brain functions. RESULTS: Brain regions with decreased ReHo were located in the left posterior cerebellar lobe in PD sub-groups compared to the HC group, and the brain regions with increased ReHo were located in the limbic lobe (right precuneus/bilateral middle cingulate cortex) in PD-MCI compared with HC group. PD-MCI presented with increased ReHo in the bilateral precuneus/left superior parietal lobe and decreased ReHo in the left insula compared to PD-NC. ReHo values for the left precuneus were negatively related to neuropsychological scores, and ReHo values for the left insula were positively related to neuropsychological scores in PD subjects. CONCLUSION: The present study demonstrated abnormal spontaneous synchrony in the left insula and left precuneus in patients with PD-MCI compared to PD-NC, which might provide a novel insight into the diagnosis and clinical treatment of cognitive impairment in PD.

Altered functional connectivity of the marginal division in Parkinson's disease with mild cognitive impairment: A pilot resting-state fMRI study.

BACKGROUND: The marginal division (MrD) is an important subcortical center involved in learning and memory. Mild cognitive impairment (MCI) is commonly seen in patients with Parkinson's disease (PD), but the neurobiological basis is yet to be elucidated. PURPOSE: To use resting-state functional magnetic resonance imaging (rs-fMRI) to explore the altered functional connectivity (FC) of the MrD in patients with PD-MCI. STUDY TYPE: Prospective pilot study. POPULATION: Twenty-five patients with PD-MCI; 25 PD patients and no cognitive impairment (PD-NCI); and 25 healthy control (HC) participants. SEQUENCE: 3.0 T GE Healthcare MRI scanner; three-dimensional T1 -weighted fast spoiled gradient recalled echo (3D T1 -FSPGR); rs-fMRI. ASSESSMENT: The MrD was defined using manual delineation, which was the seed point to compute the FC to examine correlations between low-frequency fMRI signal fluctuations in MrD and the whole brain. STATISTICAL TESTS: Between-group comparisons of the rs-fMRI data were computed using two-sample t-tests in a voxelwise manner after controlling for age and sex, to determine the brain regions that showed significant differences in FC with the bilateral MrDs. Correlation analyses were performed for FC values and cognitive abilities in patients with PD. RESULTS: In the PD-MCI group, compared with the PD-NCI group, we observed lesser FC between the MrD bilaterally and right putamen, left insula, left cerebellum, and left thalamus; greater FC between the MrD bilaterally and left middle cingulate cortex, left middle frontal gyrus, left superior frontal gyrus, left supplementary motor area, and left middle/inferior occipital gyrus. Moreover, the strength of FC between the MrD and regions that showed differences between the PD-MCI and PD-NCI groups was significantly correlated with neuropsychological scores in patients with PD. DATA CONCLUSION: The current study suggests that MrD dysfunction may contribute to MCI in PD. However, the mechanisms underlying this process require further investigation. Level of Evidence 1. Technical Efficacy Stage 2. J. Magn. Reson. Imaging 2019;50:183-192.

Acute kidney injury in China: a cross-sectional survey.

BACKGROUND: Acute kidney injury (AKI) has become a worldwide public health problem, but little information is available about the disease burden in China. We aimed to evaluate the burden of AKI and assess the availability of diagnosis and treatment in China. METHODS: We launched a nationwide, cross-sectional survey of adult patients who were admitted to hospital in 2013 in academic or local hospitals from 22 provinces in mainland China. Patients with suspected AKI were screened out on the basis of changes in serum creatinine by the Laboratory Information System, and we reviewed medical records for 2 months (January and July) to confirm diagnoses. We assessed rates of AKI according to two identification criteria: the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) AKI definition and an increase or decrease in serum creatinine by 50% during hospital stay (expanded criteria). We estimated national rates with data from the 2013 report by the Chinese National Health and Family Planning Commission and National Bureau of Statistics. FINDINGS: Of 2,223,230 patients admitted to the 44 hospitals screened in 2013, 154,950 (7·0%) were suspected of having AKI by electronic screening, of whom 26,086 patients (from 374,286 total admissions) were reviewed with medical records to confirm the diagnosis of AKI. The detection rate of AKI was 0·99% (3687 of 374,286) by KDIGO criteria and 2·03% (7604 of 374,286) by expanded criteria, from which we estimate that 1·4-2·9 million people with AKI were admitted to hospital in China in 2013. The non-recognition rate of AKI was 74·2% (5608 of 7555 with available data). Renal referral was done in 21·4% (1625 of 7604) of the AKI cases, and renal replacement therapy was done in 59·3% (531 of 896) of those who had the indications. Delayed AKI recognition was an independent risk factor for in-hospital mortality, and renal referral was an independent protective factor for AKI under-recognition and mortality INTERPRETATION: AKI has become a huge medical burden in China, with substantial underdiagnosis and undertreatment. Nephrologists should take the responsibility for leading the battle against AKI. FUNDING: National 985 Project of China, National Natural Science Foundation of China, Beijing Training Program for Talents, International Society of Nephrology Research Committee, and Bethune Fund Management Committee.

Elevated Serum Levels of NSE and S-100ß Correlate with Increased Risk of Acute Cerebral Infarction in Asian Populations.

BACKGROUND: We investigated the clinical value of serum levels of neuron-specific enolase (NSE) and human soluble protein-100ß (S-100ß) in acute cerebral infarction (ACI) patients. MATERIAL AND METHODS: A literature search of electronic databases identified relevant case-control studies that examined the correlations between NSE and S-100ß serum levels, and ACI. The retrieved studies were screened based on our strict inclusion and exclusion criteria, and high-quality studies were subsequently selected for meta-analysis. STATA software (Version 12.0, Stata Corporation, College Station, TX, USA) was utilized for statistical analysis. RESULTS: A total of 13 case-control studies, containing 911 ACI patients and 686 healthy controls, were enrolled in this meta-analysis. The results of the meta-analysis showed that serum levels of NSE and S-100ß in ACI patients were significantly higher than the control group. Subgroup analysis based on ethnicity revealed that the serum levels of NSE and S-100ß in ACI patients were significantly higher than the control group in Asian population. In Caucasian population, the serum levels of NSE in case group was significantly higher than the control group, but no significant differences in serum levels of S-100ß were observed between ACI patients and the control group. CONCLUSIONS: Based on our results, we conclude that serum levels of NSE and S-100ß strongly correlate with ACI in Asian population, and may be important clinical markers for diagnosis and treatment of ACI.

Utility of AD8 for cognitive impairment in a Chinese physical examination population: a preliminary study.

OBJECTIVE: To investigate the utility of AD8 for cognitive impairment in a Chinese physical examination population. METHODS: Military cadres who took routine physical examination in Chinese PLA General Hospital from Jan 1, 2013, to Dec 31, 2013, were subjected to AD8 scale. Individual information such as age, gender, and education was also collected. All data were analyzed by SPSS 19.0. RESULTS: 1544 subjects were enrolled in this study with mean age 75.4 ± 10.6 years. The subjects who scored 0 to 8 of AD8 scale were 1015, 269, 120, 60, 30, 14, 19, 8, and 9, respectively. Corresponding proportions were 65.7%, 17.4%, 7.8%, 3.9%, 2.0%, 0.9%, 1.2%, 0.5%, and 0.6%, respectively. The endorsement prevalence of 8 questions was 5.6%, 9.2%, 6.6%, 9.2%, 4.8%, 4.5%, 8.9%, and 24.1%, respectively. The endorsement prevalence of question 8 was significantly higher than others (P < 0.05). 260 subjects were scored equal to or greater than 2. The abnormal rate was 16.9%. All the participants were stratified into 9 groups by age; the prevalence of dementia was highly correlated with age (P < 0.01). CONCLUSION: AD8 scale is a convenient and effective tool for cognitive screening in routine physical examination population.

Using sustained vowels to identify patients with mild Parkinson's disease in a Chinese dataset.

Introduction: Parkinson's disease (PD) is the second most common neurodegenerative disease and affects millions of people. Accurate diagnosis and subsequent treatment in the early stages can slow down disease progression. However, making an accurate diagnosis of PD at an early stage is challenging. Previous studies have revealed that even for movement disorder specialists, it was difficult to differentiate patients with PD from healthy individuals until the average modified Hoehn-Yahr staging (mH&Y) reached 1.8. Recent researches have shown that dysarthria provides good indicators for computer-assisted diagnosis of patients with PD. However, few studies have focused on diagnosing patients with PD in the early stages, specifically those with mH&Y ≤ 1.5. Method: We used a machine learning algorithm to analyze voice features and developed diagnostic models for differentiating between healthy controls (HCs) and patients with PD, and for differentiating between HCs and patients with mild PD (mH&Y ≤ 1.5). The models were independently validated using separate datasets. Results: Our results demonstrate that, a remarkable diagnostic performance of the model in identifying patients with mild PD (mH&Y ≤ 1.5) and HCs, with area under the ROC curve 0.93 (95% CI: 0.851.00), accuracy 0.85, sensitivity 0.95, and specificity 0.75. Conclusion: The results of our study are helpful for screening PD in the early stages in the community and primary medical institutions where there is a lack of movement disorder specialists and special equipment.

[Efficacy and safety of ropinirole in the treatment of Parkinson's disease: a multi-center, randomized, double-blind and bromocriptine-controlled trial].

OBJECTIVE: To explore the efficacy and safety of ropinirole in the treatment of Parkinson's disease. METHODS: From November 2005 to April 2007, a total of 221 subjects from 7 hospitals of Beijing, Lanzhou and Wuhan participated in a 12-week multi-center, randomized, bromocriptine-controlled, double-blind, double-dummy and parallel-group trial. The efficacy of ropinirole was assessed with the unified Parkinson's disease rating scale (UPDRS) score, "off" time according to the patient's diary and the overall evolution of clinical efficacy. The safety was assessed on the basis of adverse events, blood pressure, pulse, laboratory measurement and electrocardiographic recordings. And the statistical analyses were performed with t, paired t, χ(2) and covariance tests. RESULTS: In the intent-to-treat population, the average UPDRSIII score decreased to (11 ± 9) in ropinirole group and (11 ± 10) in bromocriptine group while the UPDRSIIscore decreased to (4 ± 4) and (3 ± 5) respectively at Week 12 versus baseline. It showed that ropinirole was non-inferior to bromocriptine. The "off" time at Week 12 [(3.0 ± 1.2)h, (3.8 ± 1.6)h] versus baseline [(4.2 ± 2.0)h, (4.4 ± 1.7)h] decreased (t = 10.772, t = 5.746, P = 0.000) in ropinirole and bromocriptine groups. Ropinirole offered a better overall improvement rate (q = 7.241, P = 0.007). The adverse events occurring at a ratio of over 5% caused by ropinirole included orthostatic hypotension, nausea, dizziness, upper abdominal discomfort, insomnia and palpitation. No significant difference existed in the frequency of adverse events between two groups. CONCLUSIONS: Ropinirole is both effective and safe in the treatment of Chinese patients with Parkinson's disease.

Effect of blood pressure on mortality in patients with cognitive impairment: a prospective cohort study.

Background: Cognitive impairment is a prevalent condition that substantially elevates mortality rates among the elderly. The impact of hypertension on mortality in older adults with cognitive impairment is a subject of contention. This study aims to examine the influence of hypertension on both all-cause and CVD-specific mortality in elderly individuals experiencing cognitive impairment within a prospective cohort. Methods: This study encompassed 2,925 participants (weighted 53,086,905) aged 60 years or older from National Health and Nutrition Examination Survey (NHANES) spanning 2011-2014. Incidence of all-cause and CVD-specific mortality was ascertained through linkage with National Death Index records until 31 December 2019. Survival was performed employing the Kaplan-Meier method. Hazard ratios (HRs) were calculated via Cox proportional hazards regression models. Results: Over the follow-up period of up to 9.17 years [with a median (IQR) time to death of 6.58 years], equivalent to 18,731.56 (weighted 3.46 × 108) person-years, there were a total of 576 recorded deaths. Participants with CI exhibited a 1.96-fold higher risk of all-cause mortality (95% CI: 1.55-2.49; p < 0.01) and a 2.8-fold higher risk of CVD-specific mortality (95% CI: 1.83-4.29; p < 0.01) in comparison to participants without CI. Among participants with CI, concurrent hypertension comorbidity was linked to a 2.73-fold elevated risk of all-cause mortality (95% CI: 1.78-4.17; p < 0.01) and a 5.3-fold elevated risk of CVD-specific mortality (95% CI: 2.54-11.04; p < 0.01). Further stratified analyses revealed that the combined effects of hypertension and CI on all-cause and CVD-specific mortality were more pronounced in participants aged 60-69 years compared to those aged 70-80 years (p for interaction <0.01). The primary findings exhibited resilience across a series of sensitivity analyses. Conclusions: Participants with CI exhibited a markedly elevated risk of all-cause and CVD-specific mortality when coexisting with hypertension. Appropriate management of hypertension in patients with CI may be helpful in reducing the excess risk of death.

Ketogenic diet protects MPTP-induced mouse model of Parkinson's disease via altering gut microbiota and metabolites.

The ketogenic diet (KD) is a low-carbohydrate, high-fat regime that is protective against neurodegenerative diseases. However, the impact of KD on Parkinson's disease (PD) and its mechanisms remains unclear. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD was fed with KD for 8 weeks. Motor function and dopaminergic neurons were evaluated. Inflammation in the brain, plasma, and colon tissue were also measured. Fecal samples were assessed by 16S rDNA gene sequencing and untargeted metabolomics. We found that KD protected motor dysfunction, dopaminergic neuron loss, and inflammation in an MPTP mouse model of PD. 16S rDNA sequencing revealed that MPTP administration significantly increased Citrobacter, Desulfovibrio, and Ruminococcus, and decreased Dubosiella, whereas KD treatment reversed the dysbiosis. Meanwhile, KD regulated the MPTP-induced histamine, N-acetylputrescine, d-aspartic acid, and other metabolites. Fecal microbiota transplantation using feces from the KD-treated mice attenuated the motor function impairment and dopaminergic neuron loss in antibiotic-pretreated PD mice. Our current study demonstrates that KD played a neuroprotective role in the MPTP mouse model of PD through the diet-gut microbiota-brain axis, which may involve inflammation in the brain and colon. However, future research is warranted to explore the explicit anti-inflammatory mechanisms of the gut-brain axis in PD models fed with KD.

[Neuropsychological features of elderly patients with mild cognitive impairment susceptible to Alzheimer's disease].

OBJECTIVE: To explore the neuropsychological features of elderly patients with mild cognitive impairment (MCI) susceptible to Alzheimer's disease (AD). METHODS: A total of 47 patients with MCI diagnosed from June to October 2008 and 21 controls with normal cognition at the same convalescent camp were selected and followed up for two years. Montreal cognitive assessment (MoCA), mini mental state examination (MMSE) and clock drawing test (CDT) were performed for all subjects at the onset of study and repeated annually. RESULTS: At Month 12, the visuospatial skill scores of MCI patients decreased significantly versus those of the control (0.6 ± 0.7 vs 0.1 ± 0.6, P = 0.008). No one progressed to AD in neither groups. And at Month 24, both visuospatial skill scores (0.9 ± 0.9 vs 0.4 ± 0.9) and attention scores (1.0 ± 1.0 vs 0.2 ± 0.8) of MCI patients declined significantly versus the control (P = 0.021, 0.001). Among 47 MCI patients, 7 progressed to AD. No obvious difference existed in the score of all items between the AD converters and non-converters at baseline. However, the scores of MMSE (27.6 ± 0.8 vs 28.9 ± 1.0), MoCA (24.3 ± 3.1 vs 27.9 ± 1.6) and such MoCA subitems as visuospatial skill (3.9 ± 0.7 vs 4.5 ± 0.6), language (1.86 ± 0.38 vs 2.65 ± 0.53) and delayed recall (2.1 ± 1.5 vs 3.9 ± 1.0) of the converters were obviously lower than those of the non-converters at Month 12 (P < 0.05). Furthermore, all other scores of the AD converters, except for designation and abstract, were significantly lower than those of the non-converters at Month 24 (P < 0.05). CONCLUSION: The visuospatial skill, executive function, delayed recall and language function of MCI patients progressing to AD tend to have early impairment and significant changes. It may be useful to predict AD among the MCI patients.

A hybrid nanobiocatalyst with in situ encapsulated enzyme and exsolved Co nanoclusters for complete chemoenzymatic conversion of methyl parathion to 4-aminophenol.

Combination of enzymatic and chemical reactions provides tremendous possibilities for chemoenzymatic cascade processes. However, constructing efficient hybrid catalysts still faces great challenges. Herein, we develop a hybrid catalyst by in situ encapsulating organophosphorus hydrolase (OPH) into a Zn-doped Co-based ZIF (0.8CoZIF) via biomimetic mineralization for the chemoenzymatic cascade conversion of methyl parathion to 4-nitrophenol and then 4-aminophenol. The exsolved Co nanoclusters in Zn/Co-ZIF are found to catalyze 4-nitrophenol reduction into 4-aminophenol in the presence of sodium borohydride (NaBH4). The as-synthesized OPH@0.8CoZIF catalyzes the complete conversion of 95 µM methyl parathion at nearly 100% 4-aminophenol production in the presence of 50 mM NaBH4 within 15 min, which is 1/4 that of the physical mixture of OPH and 0.8CoZIF, benefiting from the MP accumulation and substrate channeling in the hybrid catalyst. The maximum cascade conversion rate of MP to 4-AP reaches 8.07 µmol·min-1·g-catalyst-1, which is higher than most of the reported chemoenzymatic cascade catalysts. Therefore, the hybrid nanocatalyst containing Co-ZIF-based catalyst and OPH is successfully fabricated and enables to catalyze the complete conversion of a toxic pollutant like methyl parathion into a non-toxic resource like 4-aminophenol for recycling in useful chemical synthesis through efficient one-pot cascade reactions.

Clinico-pathological features and mutational spectrum of 16 nemaline myopathy patients from a Chinese neuromuscular center.

Nemaline myopathy (NM) is a congenital myopathy of great heterogeneity, characterized by the presence of rods in the cytoplasm of muscle fibers. The samples of 16 nemaline myopathy patients diagnosed by characteristically pathological features went through whole exon sequencing. Clinico-pathological and genetic features of the cases were systematically analyzed. According to the classification of nemaline myopathy by ENMC, 8 cases are typical congenital subtype, 6 cases are childhood/juvenile onset subtype and 2 case are adult onset subtype. In histological findings, characteristic purple-colored rods are discovered under modified gömöri trichrome staining (MGT). Electron microscopy revealed the presence of high electron-dense nemaline bodies around the submucosa and the nucleus nine patients (9/16 56.3%) were detected pathogenic causative mutations, among whom mutations in the NEB gene were the most frequent (6 patients, 66.7%). KBTBD13 gene mutation was discovered in two patients and ACTA1 gene mutation was discovered in 1 patient. Nemaline myopathy is a congenital myopathy with highly clinico-pathological and genetic heterogeneity. NEB gene mutation is the most common mutation, in which splicing change c.21522 +3A > G is hotspot mutation in Chinese NM patients.

Effects of Ketogenic Diet on Neuroinflammation in Neurodegenerative Diseases.

The ketogenic diet (KD) is a low-carbohydrate, high-fat and adequate-protein diet. As a diet mimicking fasting, it triggers the production of ketone bodies (KBs) and brings the body into a state of ketosis. Recent and accumulating studies on humans and animal models have shown that KD is beneficial to neurodegenerative diseases through modulating central and peripheral metabolism, mitochondrial function, inflammation, oxidative stress, autophagy, and the gut microbiome. Complicated interplay of metabolism, gut microbiome, and other mechanisms can regulate neuroinflammation in neurodegenerative diseases by activating multiple molecular and cellular pathways. In this review, we detail the physiological basis of the KD, its functions in regulating neuroinflammation, and its protective role in normal brain aging and neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD). We aimed to elucidate the underlying neuroinflammatory mechanisms of KD therapies in neurodegenerative diseases and provide novel insights into their application for neurodegenerative disease prevention and treatment.

Clinical and molecular characteristics of myotonia congenita in China: Case series and a literature review.

Myotonia congenita (MC) is a rare genetic disease caused by mutations in the skeletal muscle chloride channel gene (CLCN1), encoding the voltage-gated chloride channel ClC-1 in skeletal muscle. Our study reported the clinical and molecular characteristics of six patients with MC and systematically review the literature on Chinese people. We retrospectively analyzed demographics, clinical features, family history, creatine kinase (CK), electromyography (EMG), treatment, and genotype data of our patients and reviewed the clinical data and CLCN1 mutations in literature. The median ages at examination and onset were 26.5 years (range 11-50 years) and 6.5 years (range 1.5-11 years), respectively, in our patients, and 21 years (range 3.5-65 years, n = 45) and 9 years (range 0.5-26 years, n = 50), respectively, in literature. Similar to previous reports, myotonia involved limb, lids, masticatory, and trunk muscles to varying degrees. Warm-up phenomenon (5/6), percussion myotonia (3/5), and grip myotonia (6/6) were common. Menstruation triggered myotonia in females, not observed in Chinese patients before. The proportion of abnormal CK levels (4/5) was higher than data from literature. Electromyography performed in six patients revealed myotonic changes (100%). Five novel CLCN1 mutations, including a splicing mutation (c.853 + 4A>G), a deletion mutation (c.2010_2014del), and three missense mutations (c.2527C>T, c.1727C>T, c.2017 G > C), were identified. The c.892 G > A (p.A298T) mutation was the most frequent mutation in the Chinese population. Our study expanded the clinical and genetic spectrum of patients with MC in the China. The MC phenotype in Chinese people is not different from that found in the West, while the genotype is different.