Gut microbiome features and metabolites in non-alcoholic fatty liver disease among community-dwelling middle-aged and older adults.

BACKGROUND: The specific microbiota and associated metabolites linked to non-alcoholic fatty liver disease (NAFLD) are still controversial. Thus, we aimed to understand how the core gut microbiota and metabolites impact NAFLD. METHODS: The data for the discovery cohort were collected from the Guangzhou Nutrition and Health Study (GNHS) follow-up conducted between 2014 and 2018. We collected 272 metadata points from 1546 individuals. The metadata were input into four interpretable machine learning models to identify important gut microbiota associated with NAFLD. These models were subsequently applied to two validation cohorts [the internal validation cohort (n = 377), and the prospective validation cohort (n = 749)] to assess generalizability. We constructed an individual microbiome risk score (MRS) based on the identified gut microbiota and conducted animal faecal microbiome transplantation experiment using faecal samples from individuals with different levels of MRS to determine the relationship between MRS and NAFLD. Additionally, we conducted targeted metabolomic sequencing of faecal samples to analyse potential metabolites. RESULTS: Among the four machine learning models used, the lightGBM algorithm achieved the best performance. A total of 12 taxa-related features of the microbiota were selected by the lightGBM algorithm and further used to calculate the MRS. Increased MRS was positively associated with the presence of NAFLD, with odds ratio (OR) of 1.86 (1.72, 2.02) per 1-unit increase in MRS. An elevated abundance of the faecal microbiota (f__veillonellaceae) was associated with increased NAFLD risk, whereas f__rikenellaceae, f__barnesiellaceae, and s__adolescentis were associated with a decreased presence of NAFLD. Higher levels of specific gut microbiota-derived metabolites of bile acids (taurocholic acid) might be positively associated with both a higher MRS and NAFLD risk. FMT in mice further confirmed a causal association between a higher MRS and the development of NAFLD. CONCLUSIONS: We confirmed that an alteration in the composition of the core gut microbiota might be biologically relevant to NAFLD development. Our work demonstrated the role of the microbiota in the development of NAFLD.

Two-week continuous glucose monitoring-derived metrics and degree of hepatic steatosis: a cross-sectional study among Chinese middle-aged and elderly participants.

BACKGROUND: Continuous glucose monitoring (CGM) devices provide detailed information on daily glucose control and glycemic variability. Yet limited population-based studies have explored the association between CGM metrics and fatty liver. We aimed to investigate the associations of CGM metrics with the degree of hepatic steatosis. METHODS: This cross-sectional study included 1180 participants from the Guangzhou Nutrition and Health Study. CGM metrics, covering mean glucose level, glycemic variability, and in-range measures, were separately processed for all-day, nighttime, and daytime periods. Hepatic steatosis degree (healthy: n = 698; mild steatosis: n = 242; moderate/severe steatosis: n = 240) was determined by magnetic resonance imaging proton density fat fraction. Multivariate ordinal logistic regression models were conducted to estimate the associations between CGM metrics and steatosis degree. Machine learning models were employed to evaluate the predictive performance of CGM metrics for steatosis degree. RESULTS: Mean blood glucose, coefficient of variation (CV) of glucose, mean amplitude of glucose excursions (MAGE), and mean of daily differences (MODD) were positively associated with steatosis degree, with corresponding odds ratios (ORs) and 95% confidence intervals (CIs) of 1.35 (1.17, 1.56), 1.21 (1.06, 1.39), 1.37 (1.19, 1.57), and 1.35 (1.17, 1.56) during all-day period. Notably, lower daytime time in range (TIR) and higher nighttime TIR were associated with higher steatosis degree, with ORs (95% CIs) of 0.83 (0.73, 0.95) and 1.16 (1.00, 1.33), respectively. For moderate/severe steatosis (vs. healthy) prediction, the average area under the receiver operating characteristic curves were higher for the nighttime (0.69) and daytime (0.66) metrics than that of all-day metrics (0.63, P < 0.001 for all comparisons). The model combining both nighttime and daytime metrics achieved the highest predictive capacity (0.73), with nighttime MODD emerging as the most important predictor. CONCLUSIONS: Higher CGM-derived mean glucose and glycemic variability were linked with higher steatosis degree. CGM-derived metrics during nighttime and daytime provided distinct and complementary insights into hepatic steatosis.

Perturbational complexity index in assessing responsiveness to rTMS treatment in patients with disorders of consciousness: a cross-over randomized controlled trial study.

BACKGROUND: Disorders of Consciousness (DoC) caused by severe brain injuries represent a challenging clinical entity, which is easy to misdiagnosis and lacks effective treatment options. Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive neuroelectric stimulation method that shows promise in improving consciousness for DoC, especially in minimally conscious state (MCS). However, there is little evidence of its effectiveness, especially in RCT studies. METHODS: Twenty MCS patients participated in a double-blind, randomized, crossover, sham-controlled clinical study to evaluate the safety and efficacy of rTMS for MCS. Subjects were randomized into two groups: one group received rTMS-active for 10 consecutive days (n = 10), and the other group received rTMS-sham for 10 consecutive days (n = 10). After a 10-day washout period, the two groups were crossed over and received the opposite treatment. the rTMS protocol consisted of 2,000 pulses per day in the left dorsolateral prefrontal cortex (L-DLPFC), sent at 10 Hz. The stimulation intensity was 90% of the resting motor threshold. Coma Recovery Scale Revised (CRS-R), the main evaluation index, was evaluated before and after each phase in a double-blind manner. Meanwhile RS-EEG and TMS-EEG data were acquired and relative alpha power (RAP), and perturbational complexity index based on state transitions (PCIst) were caculated. RESULTS: One-way ANOVA revealed significantly higher scores in rTMS-active treatment compared to rTMS-sham across various measures, including CRS-R total score, RAP, PCIst (all P < 0.05). Among the 20 MCS patients, 7 (35%) were identified as responders following rTMS treatment. Compared to rTMS-sham, responder scores for CRS-R, RAP, and PCIst (all P < 0.05) were significantly elevated after rTMS-active treatment. Conversely, there was no significant difference observed in non-responders. Furthermore, post-hoc analysis revealed that baseline PCIst was significantly higher in responders than non-responders. Upon a 6-month follow-up, CRS-R scores significantly increased in all 20 patients (P = 0.026). However, the responder group exhibited a more favorable prognosis compared to the non-responder group (P = 0.031). CONCLUSIONS: Applying 10 Hz rTMS to L-DLPFC significantly increased consciousness level in MCS patients. PCIst is a neurophysiological index that has the potential to evaluate and predict therapeutic efficacy. TRIAL REGISTRATION: www. CLINICALTRIALS: gov , identifier: NCT05187000.

Cohort Profile: Guangzhou Nutrition and Health Study (GNHS): A Population-Based Multi-Omics Study.

BACKGROUND: The Guangzhou Nutrition and Health Study (GNHS) aims to assess the determinants of metabolic disease in nutritional aspects, as well as other environmental and genetic factors, and explore possible biomarkers and mechanisms with multi-omics integration. METHODS: The population-based sample of adults in Guangzhou, China (baseline: 40-83 years old; n = 5118) was followed up about every 3 years. All will be tracked via on-site follow-up and health information systems. We assessed detailed information on lifestyle factors, physical activities, dietary assessments, psychological health, cognitive function, body measurements, and muscle function. Instrument tests included dual-energy X-ray absorptiometry scanning, carotid artery and liver ultrasonography evaluations, vascular endothelial function evaluation, upper-abdomen and brain magnetic resonance imaging, and 14-d real-time continuous glucose monitoring tests. We also measured multi-omics, including host genome-wide genotyping, serum metabolome and proteome, gut microbiome (16S rRNA sequencing, metagenome, and internal transcribed spacer 2 sequencing), and fecal metabolome and proteome. RESULTS: The baseline surveys were conducted from 2008 to 2015. Now, we have completed 3 waves. The 3rd and 4th follow-ups have started but have yet to end. A total of 5118 participants aged 40-83 took part in the study. The median age at baseline was approximately 59.0 years and the proportion of female participants was about 69.4%. Among all the participants, 3628 (71%) completed at least one on-site follow-up with a median duration of 9.48 years. CONCLUSION: The cohort will provide data that have been influential in establishing the role of nutrition in metabolic diseases with multi-omics.

Mapping the human gut mycobiome in middle-aged and elderly adults: multiomics insights and implications for host metabolic health.

OBJECTIVE: The human gut fungal community, known as the mycobiome, plays a fundamental role in the gut ecosystem and health. Here we aimed to investigate the determinants and long-term stability of gut mycobiome among middle-aged and elderly adults. We further explored the interplay between gut fungi and bacteria on metabolic health. DESIGN: The present study included 1244 participants from the Guangzhou Nutrition and Health Study. We characterised the long-term stability and determinants of the human gut mycobiome, especially long-term habitual dietary consumption. The comprehensive multiomics analyses were performed to investigate the ecological links between gut bacteria, fungi and faecal metabolome. Finally, we examined whether the interaction between gut bacteria and fungi could modulate the metabolic risk. RESULTS: The gut fungal composition was temporally stable and mainly determined by age, long-term habitual diet and host physiological states. Specifically, compared with middle-aged individuals, Blastobotrys and Agaricomycetes spp were depleted, while Malassezia was enriched in the elderly. Dairy consumption was positively associated with Saccharomyces but inversely associated with Candida. Notably, Saccharomycetales spp interacted with gut bacterial diversity to influence insulin resistance. Bidirectional mediation analyses indicated that bacterial function or faecal histidine might causally mediate an impact of Pichia on blood cholesterol. CONCLUSION: We depict the sociodemographic and dietary determinants of human gut mycobiome in middle-aged and elderly individuals, and further reveal that the gut mycobiome may be closely associated with the host metabolic health through regulating gut bacterial functions and metabolites.

Change of soluble acid invertase gene (SAI-1) haplotype in hybrid sorghum breeding program in China.

Sugar metabolism is the most important and core one which drives plant growth and development. Invertases are key enzymes that regulate sugar metabolism. A still-growing number of studies have revealed that invertases play a crucial role in various aspects of plant growth and development. Crop yield is the product of sugar metabolism; it could be deduced that invertase also regulated the yield formation. So we have done a series of research on soluble acid invertase in sweet sorghum from enzyme activity to gene cloning and functional marker development. In this paper, we sequenced full length of SAI-1 gene in 69 grain sorghum parent lines, trying to see how it differs in their gene sequences and their distribution in related hybrid varieties released in the past. To our surprise, the result showed that B-lines and restore lines (R-line) have almost different SAI-1 haplotype distribution. The change of haplotype of SAI-1 gene is associated with yield gain as with grain sorghum breeding progress, which proved that SAI-1 may take a very important role in yield formation. And we also found the SAI-1 gene tends to become shorter as with the breeding advance, which means short sequence in introns, while exon remains unchanged leading to higher gene efficiency. The best SAI-1 haplotype combination of sorghum hybrid was also found for different planting regions. These findings are of great significance for improving breeding efficiency, understanding heterosis, and germplasm enhancement. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-021-01231-2.

Higher Healthy Lifestyle Score is associated with lower presence of non-alcoholic fatty liver disease in middle-aged and older Chinese adults: a community-based cross-sectional study.

OBJECTIVE: Previous studies have reported inverse associations between certain healthy lifestyle factors and non-alcoholic fatty liver disease (NAFLD), but limited evidence showed the synergistic effect of those lifestyles. This study examined the relationship of a combination of lifestyles, expressed as Healthy Lifestyle Score (HLS), with NAFLD. DESIGN: A community-based cross-sectional study. Questionnaires and body assessments were used to collect data on the six-item HLS (ranging from 0 to 6, where higher scores indicate better health). The HLS consists of non-smoking (no active or passive smoking), normal BMI (18·5-23·9 kg/m2), physical activity (moderate or vigorous physical activity ≥ 150 min/week), healthy diet pattern, good sleep (no insomnia or <6 months) and no anxiety (Self-rating Anxiety Scale < 50), one point each. NAFLD was diagnosed by ultrasonography. SETTING: Guangzhou, China. PARTICIPANTS: Two thousand nine hundred and eighty-one participants aged 40-75 years. RESULTS: The overall prevalence of NAFLD was 50·8 %. After adjusting for potential covariates, HLS was associated with lower presence of NAFLD. The OR of NAFLD for subjects with higher HLS (3, 4, 5-6 v. 0-1 points) were 0·68 (95 % CI 0·51, 0·91), 0·58 (95 % CI 0·43, 0·78) and 0·35 (95 % CI 0·25, 0·51), respectively (P-values < 0·05). Among the six items, BMI and physical activity were the strongest contributors. Sensitivity analyses showed that the association was more significant after weighting the HLS. The beneficial association remained after excluding any one of the six components or replacing BMI with waist circumference. CONCLUSIONS: Higher HLS was associated with lower presence of NAFLD, suggesting that a healthy lifestyle pattern might be beneficial to liver health.

Increased Adrenocorticotropic Hormone Levels Predict Recovery of Consciousness in Patients With Disorders of Consciousness.

The potential influence of pituitary-related hormones (including both pituitary gland and target gland hormones) on functional recovery after traumatic brain injury has been observed. However, the relationship between these hormones and the recovery of consciousness in patients with disorders of consciousness (DOC) remains unclear. In this retrospective and observational study, 208 patients with DOC were recruited. According to the Glasgow Outcome Scale (GOS) scores after 6 months, patients with DOC were categorized into two subgroups: a favorable prognosis subgroup (n = 38) comprising those who regained consciousness (GOS score ≥3), and a poor prognosis subgroup (n = 156) comprising those who remained in DOC (GOS score <3). Comparative analyses of pituitary-related hormone levels between the two subgroups were conducted. Further, a binary logistic regression analysis was conducted to assess the predictive value of pituitary-related hormones for the patients' prognosis. The favorable prognosis subgroup showed a significant increase in adrenocorticotropic hormone (ACTH) levels (p = 0.036). Moreover, higher ACTH levels and shorter days since injury were significantly associated with a better prognosis, with odds ratios (ORs) of 0.928 (95% confidence interval [CI] = 0.873-0.985, p = 0.014) and 1.015 (95% CI = 1.005-1.026, p = 0.005), respectively. A subsequent receiver operating characteristic (ROC) analysis demonstrated the potential to predict patients' prognosis with an area under the curve value of 0.78, an overall accuracy of 75.5%, a sensitivity of 77.5%, and a specificity of 66.7%. Our findings indicate that ACTH levels could serve as a clinically valuable and convenient predictor for patients' prognosis.

Closed-loop transcutaneous auricular vagus nerve stimulation for the improvement of upper extremity motor function in stroke patients: a study protocol.

Background: Transcutaneous auricular vagus nerve stimulation (taVNS) has garnered attention for stroke rehabilitation, with studies demonstrating its benefits when combined with motor rehabilitative training or delivered before motor training. The necessity of concurrently applying taVNS with motor training for post-stroke motor rehabilitation remains unclear. We aimed to investigate the necessity and advantages of applying the taVNS concurrently with motor training by an electromyography (EMG)-triggered closed-loop system for post-stroke rehabilitation. Methods: We propose a double-blinded, randomized clinical trial involving 150 stroke patients assigned to one of three groups: concurrent taVNS, sequential taVNS, or sham control condition. In the concurrent group, taVNS bursts will synchronize with upper extremity motor movements with EMG-triggered closed-loop system during the rehabilitative training, while in the sequential group, a taVNS session will precede the motor rehabilitative training. TaVNS intensity will be set below the pain threshold for both concurrent and sequential conditions and at zero for the control condition. The primary outcome measure is the Fugl-Meyer Assessment of Upper Extremity (FMA-UE). Secondary measures include standard upper limb function assessments, as well as EMG and electrocardiogram (ECG) features. Ethics and dissemination: Ethical approval has been granted by the Medical Ethics Committee, affiliated with Zhujiang Hospital of Southern Medical University for Clinical Studies (2023-QX-012-01). This study has been registered on ClinicalTrials (NCT05943431). Signed informed consent will be obtained from all included participants. The findings will be published in peer-reviewed journals and presented at relevant stakeholder conferences and meetings. Discussion: This study represents a pioneering effort in directly comparing the impact of concurrent taVNS with motor training to that of sequential taVNS with motor training on stroke rehabilitation. Secondly, the incorporation of an EMG-triggered closed-loop taVNS system has enabled the automation and individualization of both taVNS and diverse motor training tasks-a novel approach not explored in previous research. This technological advancement holds promise for delivering more precise and tailored training interventions for stroke patients. However, it is essential to acknowledge a limitation of this study, as it does not delve into examining the neural mechanisms underlying taVNS in the context of post-stroke rehabilitation.

Individualized music induces theta-gamma phase-amplitude coupling in patients with disorders of consciousness.

Objective: This study aimed to determine whether patients with disorders of consciousness (DoC) could experience neural entrainment to individualized music, which explored the cross-modal influences of music on patients with DoC through phase-amplitude coupling (PAC). Furthermore, the study assessed the efficacy of individualized music or preferred music (PM) versus relaxing music (RM) in impacting patient outcomes, and examined the role of cross-modal influences in determining these outcomes. Methods: Thirty-two patients with DoC [17 with vegetative state/unresponsive wakefulness syndrome (VS/UWS) and 15 with minimally conscious state (MCS)], alongside 16 healthy controls (HCs), were recruited for this study. Neural activities in the frontal-parietal network were recorded using scalp electroencephalography (EEG) during baseline (BL), RM and PM. Cerebral-acoustic coherence (CACoh) was explored to investigate participants' abilitiy to track music, meanwhile, the phase-amplitude coupling (PAC) was utilized to evaluate the cross-modal influences of music. Three months post-intervention, the outcomes of patients with DoC were followed up using the Coma Recovery Scale-Revised (CRS-R). Results: HCs and patients with MCS showed higher CACoh compared to VS/UWS patients within musical pulse frequency (p = 0.016, p = 0.045; p < 0.001, p = 0.048, for RM and PM, respectively, following Bonferroni correction). Only theta-gamma PAC demonstrated a significant interaction effect between groups and music conditions (F (2,44) = 2.685, p = 0.036). For HCs, the theta-gamma PAC in the frontal-parietal network was stronger in the PM condition compared to the RM (p = 0.016) and BL condition (p < 0.001). For patients with MCS, the theta-gamma PAC was stronger in the PM than in the BL (p = 0.040), while no difference was observed among the three music conditions in patients with VS/UWS. Additionally, we found that MCS patients who showed improved outcomes after 3 months exhibited evident neural responses to preferred music (p = 0.019). Furthermore, the ratio of theta-gamma coupling changes in PM relative to BL could predict clinical outcomes in MCS patients (r = 0.992, p < 0.001). Conclusion: Individualized music may serve as a potential therapeutic method for patients with DoC through cross-modal influences, which rely on enhanced theta-gamma PAC within the consciousness-related network.

Effects of 10 Hz individualized repetitive transcranial magnetic stimulation on patients with disorders of consciousness: a study protocol for an exploratory double-blind crossover randomized sham-controlled trial.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS), as a non-invasive brain stimulation technique, has shown potentials for consciousness recovery of patients with disorders of consciousness (DoC), as, to a certain extent, it is effective in regulating the excitability of central nervous system. However, it is difficult to achieve satisfactory effect with "one size fits all" rTMS treatment due to different clinical conditions of patients. There is an urgent need to develop individualized strategy to improve the effectiveness of rTMS on patients with DoC. METHODS: Our protocol is a randomized double-blind sham-controlled crossover trial that includes 30 DoC patients. Each patient will received 20 sessions, in which 10 sessions will be rTMS-active stimulus, and the other 10 sessions will be sham stimulus, separated by no less than 10 days' washout period. The rTMS-active will include 10 Hz rTMS over the individualized-targeted selection area for each patient according to the different insult regions of the brain. Coma Recovery Scale-Revised (CRS-R) will be used as primary outcome at baseline, after the first stage of stimulation, at the end of the washout period, and after the second stage of stimulation. Secondary outcomes will be measured at the same time, including efficiency, relative spectral power, and functional connectivity of high-density electroencephalograph (EEG). Adverse events will be recorded during the study. DISCUSSION: rTMS has obtained grade A evidence in treating patients with several central nervous system diseases, and there has been some evidence showing partial improvement on level of consciousness in DoC patients. However, the effectiveness of rTMS in DoC is only 30~36%, mostly due to the non-specific target selection. In this protocol, we present a double-blind crossover randomized sham-controlled trial based on the individualized-targeted selection strategy that aims to study the effectiveness of rTMS therapy for DoC, and the result may provide new insights to non-invasive brain stimulation. TRIAL REGISTRATION: ClinicalTrials.gov : NCT05187000. Registered on January 10, 2022.

Repetitive transcranial magnetic stimulation over the posterior parietal cortex improves functional recovery in nonresponsive patients: A crossover, randomized, double-blind, sham-controlled study.

Background: Recent studies have shown that patients with disorders of consciousness (DoC) can benefit from repetitive transcranial magnetic stimulation (rTMS) therapy. The posterior parietal cortex (PPC) is becoming increasingly important in neuroscience research and clinical treatment for DoC as it plays a crucial role in the formation of human consciousness. However, the effect of rTMS on the PPC in improving consciousness recovery remains to be studied. Method: We conducted a crossover, randomized, double-blind, sham-controlled clinical study to assess the efficacy and safety of 10 Hz rTMS over the left PPC in unresponsive patients. Twenty patients with unresponsive wakefulness syndrome were recruited. The participants were randomly divided into two groups: one group received active rTMS treatment for 10 consecutive days (n = 10) and the other group received sham treatment for the same period (n = 10). After a 10-day washout period, the groups crossed over and received the opposite treatment. The rTMS protocol involved the delivery of 2000 pulses/day at a frequency of 10 Hz, targeting the left PPC (P3 electrode sites) at 90% of the resting motor threshold. The primary outcome measure was the JFK Coma Recovery Scele-Revised (CRS-R), and evaluations were conducted blindly. EEG power spectrum assessments were also conducted simultaneously before and after each stage of the intervention. Result: rTMS-active treatment resulted in a significant improvement in the CRS-R total score (F = 8.443, p = 0.009) and the relative alpha power (F = 11.166, p = 0.004) compared to sham treatment. Furthermore, 8 out of 20 patients classified as rTMS responders showed improvement and evolved to a minimally conscious state (MCS) as a result of active rTMS. The relative alpha power also significantly improved in responders (F = 26.372, p = 0.002) but not in non-responders (F = 0.704, p = 0.421). No adverse effects related to rTMS were reported in the study. Conclusions: This study suggests that 10 Hz rTMS over the left PPC can significantly improve functional recovery in unresponsive patients with DoC, with no reported side effects. Clinical trial registration: www.ClinicalTrials.gov, identifier: NCT05187000.

Olfactory response is a potential sign of consciousness: electroencephalogram findings.

Objective: This study aimed to explore whether olfactory response can be a sign of consciousness and represent higher cognitive processing in patients with disorders of consciousness (DoC) using clinical and electroencephalogram data. Methods: Twenty-eight patients with DoC [13 vegetative states (VS)/unresponsive wakefulness syndrome (UWS) and 15 minimally conscious states (MCS)] were divided into two groups: the presence of olfactory response (ORES) group and the absence of olfactory response (N-ORES) group according to behavioral signs from different odors, i.e., vanillin, decanoic acid, and blank stimuli. We recorded an olfactory task-related electroencephalogram (EEG) and analyzed the relative power and functional connectivity at the whole-brain level in patients with DoC and healthy controls (HCs). After three months, the outcomes of DoC patients were followed up using the coma recovery scale-revised (CRS-R). Results: A significant relationship was found between olfactory responses and the level of consciousness (χ2(1) = 6.892, p = 0.020). For olfactory EEG, N-ORES patients showed higher theta functional connectivity than ORES patients after stimulation with vanillin (p = 0.029; p = 0.027). Patients with N-ORES showed lower alpha and beta relative powers than HCs at the group level (p = 0.019; p = 0.033). After three months, 62.5% (10/16) of the ORES patients recovered consciousness compared to 16.7% (2/12) in the N-ORES group. The presence of olfactory response was significantly associated with an improvement in consciousness (χ2(1) = 5.882, p = 0.023). Conclusion: Olfactory responses should be considered signs of consciousness. The differences in olfactory processing between DoC patients with and without olfactory responses may be a way to explore the neural correlates of olfactory consciousness in these patients. The olfactory response may help in the assessment of consciousness and may contribute to therapeutic orientation.

Is frontoparietal electroencephalogram activity related to the level of functional disability in patients emerging from a minimally conscious state? A preliminary study.

Objective: When regaining consciousness, patients who emerge from a minimally conscious state (EMCS) present with different levels of functional disability, which pose great challenges for treatment. This study investigated the frontoparietal activity in EMCS patients and its effects on functional disability. Materials and methods: In this preliminary study, 12 EMCS patients and 12 healthy controls were recruited. We recorded a resting-state scalp electroencephalogram (EEG) for at least 5 min for each participant. Each patient was assessed using the disability rating scale (DRS) to determine the level of functional disability. We analyzed the EEG power spectral density and sensor-level functional connectivity in relation to the patient's functional disability. Results: In the frontoparietal region, EMCS patients demonstrated lower relative beta power (P < 0.01) and higher weighted phase lag index (wPLI) values in the theta (P < 0.01) and gamma (P < 0.01) bands than healthy controls. The frontoparietal theta wPLI values of EMCS patients were positively correlated with the DRS scores (r s = 0.629, P = 0.029). At the whole-brain level, EMCS patients only had higher wPLI values in the theta band (P < 0.01) than healthy controls. The whole-brain theta wPLI values of EMCS patients were also positively correlated with the DRS scores (r s = 0.650, P = 0.022). No significant difference in the power and connectivity between the frontoparietal region and the whole brain in EMCS patients was observed. Conclusion: EMCS patients still experience neural dysfunction, especially in the frontoparietal region. However, the theta connectivity in the frontoparietal region did not increase specifically. At the level of the whole brain, the same shift could also be seen. Theta functional connectivity in the whole brain may underlie different levels of functional disability.

Higher serum vitamin A is associated with a worsened progression of non-alcoholic fatty liver disease in adults: a prospective study.

Background: The association between serum vitamin A and non-alcoholic fatty liver disease (NAFLD) remains uncertain due to inconsistent results and scarce longitudinal data. We examined the prospective associations between serum vitamin A and the evolution of the NAFLD severity score as well as the potential mediating effects in middle-aged and older Chinese adults. Method: A total of 2658 adults (between 40-75 years of age) were included in the analysis. We determined the serum concentrations of vitamin A at the onset of the study (the baseline), and the degree of NAFLD after years 3 and 6. Results: Subjects were classified into stable, progressed, and improved groups according to the changes in their severity score (0-3) of NAFLD between two visits. Analyses of covariance showed that the serum VA concentrations were positively associated with NAFLD progression (all p-trend < 0.05). After adjusting for potential confounders, the mean differences in the serum vitamin A were 7.7% lower in the improved group than those in the progressed group among the total population. Path analyses showed that vitamin A was positively associated with the serum retinol-binding protein 4, triglycerides, insulin resistance, and body mass index (standardized ß 0.065-0.304, all p < 0.001), and all of these factors positively correlated with the prevalence and progression of NAFLD (standardized ß 0.045-0.384, all p < 0.01). Conclusions: A higher serum vitamin A concentration was associated with NAFLD progression, which might be mediated by increases in the serum retinol-binding protein 4, triglycerides, insulin resistance, and body mass index.

Gut microbiome, cognitive function and brain structure: a multi-omics integration analysis.

BACKGROUND: Microbiome-gut-brain axis may be involved in the progression of age-related cognitive impairment and relevant brain structure changes, but evidence from large human cohorts is lacking. This study was aimed to investigate the associations of gut microbiome with cognitive impairment and brain structure based on multi-omics from three independent populations. METHODS: We included 1430 participants from the Guangzhou Nutrition and Health Study (GNHS) with both gut microbiome and cognitive assessment data available as a discovery cohort, of whom 272 individuals provided fecal samples twice before cognitive assessment. We selected 208 individuals with baseline microbiome data for brain magnetic resonance imaging during the follow-up visit. Fecal 16S rRNA and shotgun metagenomic sequencing, targeted serum metabolomics, and cytokine measurements were performed in the GNHS. The validation analyses were conducted in an Alzheimer's disease case-control study (replication study 1, n = 90) and another community-based cohort (replication study 2, n = 1300) with cross-sectional dataset. RESULTS: We found protective associations of specific gut microbial genera (Odoribacter, Butyricimonas, and Bacteroides) with cognitive impairment in both the discovery cohort and the replication study 1. Result of Bacteroides was further validated in the replication study 2. Odoribacter was positively associated with hippocampal volume (ß, 0.16; 95% CI 0.06-0.26, P = 0.002), which might be mediated by acetic acids. Increased intra-individual alterations in gut microbial composition were found in participants with cognitive impairment. We also identified several serum metabolites and inflammation-associated metagenomic species and pathways linked to impaired cognition. CONCLUSIONS: Our findings reveal that specific gut microbial features are closely associated with cognitive impairment and decreased hippocampal volume, which may play an important role in dementia development.

Physical performance and risk of hip fracture in community-dwelling elderly people in China: A 4-year longitudinal cohort study.

BACKGROUND: This study aims to evaluate the association between the risk of hip fracture and score on the Short Physical Performance Battery (SPPB) and handgrip strength in community-dwelling elderly people in China. METHODS: A total of 5,958 community-dwelling Chinese people aged 60 years or more from the China Health and Retirement Longitudinal Study (CHARLS) were surveyed in 2011 (baseline) and followed through to 2016. Score on the SPPB (which comprises tests of balance, walking speed, and repeated chair stands) and handgrip strength were determined at baseline. Binary logistic regression models were used to estimate the risk ratio (RR) and 95 % CI. RESULT: During an average of approximately 4 years of follow-up, 180 (3.0 %) participants experienced incident hip fracture. After multivariate adjustment, the overall SPPB score and repeated chair stands alone distinguished a gradient of hip fracture risks. The risk of hip fracture was 1.65-fold higher in poor SPPB performers (score 0-6) than in good SPPB performers (score 10-12). Participants unable to complete repeated chair stands, and those who took ≥16.7 s or 13.7-16.6 s to complete them, had a higher risk than those who took ≤ 11.1 s to complete them, with RRs of 2.45, 2.12, and 1.93, respectively. Participants unable to complete the balance tests had a higher hip fracture risk than those with scores of 4, with an RR of 2.16. Walking speed and handgrip strength were not associated with increased hip fracture risk. CONCLUSION: Among community-dwelling elderly Chinese people, overall SPPB score, as well as performance on repeated chair stands and balance tests within the SPPB, were significantly and independently associated with increased hip fracture risk. These indicators could be used to predict hip fracture in clinical settings.

Reduction of Silent Information Regulator 1 Activates Interleukin-33/ST2 Signaling and Contributes to Neuropathic Pain Induced by Spared Nerve Injury in Rats.

Emerging studies have demonstrated that interleukin (IL)-33 and its receptor ST2 act as key factors in inflammatory diseases. Moreover, accumulating evidence has suggested that cytokines, including tumor necrosis factor (TNF)-α and IL-1ß, trigger an inflammatory cascade. SIRT1 has been shown to suppress the expression of inflammatory cytokines. However, the effects of SIRT1 on IL-33/ST2 signaling and initiation of the inflammatory cascade via modulation of TNF-α and IL-1ß by IL-33 remain unclear. In the present study, we found that the dorsal root ganglion (DRG) IL-33 and ST2 were upregulated in a rat model of spared nerve injury (SNI) and intrathecal injection of either IL-33 or ST2 antibodies alleviated mechanical allodynia and downregulated TNF-α and IL-1ß induced by SNI. In addition, activation of SIRT1 decreased enhanced DRG IL-33/ST2 signaling in SNI rats. Artificial inactivation of SIRT1 via intrathecal injection of an SIRT1 antagonist could induce mechanical allodynia and upregulate IL-33 and ST2. These results demonstrated that reduction in SIRT1 could induce upregulation of DRG IL-33 and ST2 and contribute to mechanical allodynia induced by SNI in rats.

Recommendation of Antimicrobial Dosing Optimization During Continuous Renal Replacement Therapy.

Continuous Renal Replacement Therapy (CRRT) is more and more widely used in patients for various indications recent years. It is still intricate for clinicians to decide a suitable empiric antimicrobial dosing for patients receiving CRRT. Inappropriate doses of antimicrobial agents may lead to treatment failure or drug resistance of pathogens. CRRT factors, patient individual conditions and drug pharmacokinetics/pharmacodynamics are the main elements effecting the antimicrobial dosing adjustment. With the development of CRRT techniques, some antimicrobial dosing recommendations in earlier studies were no longer appropriate for clinical use now. Here, we reviewed the literatures involving in new progresses of antimicrobial dosages, and complied the updated empirical dosing strategies based on CRRT modalities and effluent flow rates. The following antimicrobial agents were included for review: flucloxacillin, piperacillin/tazobactam, ceftriaxone, ceftazidime/avibactam, cefepime, ceftolozane/tazobactam, sulbactam, meropenem, imipenem, panipenem, biapenem, ertapenem, doripenem, amikacin, ciprofloxacin, levofloxacin, moxifloxacin, clindamycin, azithromycin, tigecycline, polymyxin B, colistin, vancomycin, teicoplanin, linezolid, daptomycin, sulfamethoxazole/trimethoprim, fluconazole, voriconazole, posaconzole, caspofungin, micafungin, amphotericin B, acyclovir, ganciclovir, oseltamivir, and peramivir.

Pharmacotherapics Advice in Guidelines for COVID-19.

Since December 2019 to May 2020, coronavirus disease 2019 (COVID-19) has infected over 6 million people worldwide. Due to its sudden and rapid outbreak, effective treatment for COVID-19 is scarce. Based on national clinical trials of novel treatments, China, Italy, Germany, and other countries and organizations have published multiple guidelines for COVID-19 and advised many medicines, such as chloroquine and tocilizumab. In this paper, we summarize the pharmacotherapy for COVID-19 according to those guidelines, highlight updates of the pharmacotherapy guidelines, and review the efficacy and safety of the indicated anti-COVID-19 drugs.