Lactobacillus casei-fermented Amomum xanthioides ameliorates metabolic dysfunction in high-fat diet-induced obese mice.

Amomum xanthioides (AX) has been used as an edible herbal medicine to treat digestive system disorders in Asia. Additionally, Lactobacillus casei is a well-known probiotic commonly used in fermentation processes as a starter. The current study aimed to investigate the potential of Lactobacillus casei-fermented Amomum xanthioides (LAX) in alleviating metabolic disorders induced by high-fat diet (HFD) in a mouse model. LAX significantly reduced the body and fat weight, outperforming AX, yet without suppressing appetite. LAX also markedly ameliorated excessive lipid accumulation and reduced inflammatory cytokine (IL-6) levels in serum superior to AX in association with UCP1 activation and adiponectin elevation. Furthermore, LAX noticeably improved the levels of fasting blood glucose, serum insulin, and HOMA-IR through positive regulation of glucose transporters (GLUT2, GLUT4), and insulin receptor gene expression. In conclusion, the fermentation of AX demonstrates a pronounced mitigation of overnutrition-induced metabolic dysfunction, including hyperlipidemia, hyperglycemia, hyperinsulinemia, and obesity, compared to non-fermented AX. Consequently, we proposed that the fermentation of AX holds promise as a potential candidate for effectively ameliorating metabolic disorders.

The 90% effective dose (ED90) of remimazolam for inhibiting responses to the insertion of a duodenoscope during ERCP.

BACKGROUND: Compared to midazolam, remimazolam has a faster onset and offset of hypnotic effect, as well as cardiorespiratory stability, this study aims to determine the 90% effective dose (ED90) of remimazolam to inhibit responses to insertion of a duodenoscope during endoscopic retrograde cholangiopancreatography (ERCP). METHODS: A dose-response study was carried out undergoing ERCP who received remimazolam-alfentanil anesthesia using 10 µg/kg of alfentanil between September 2021 and November 2021. The initial dose of remimazolam was 0.2 mg/kg. The dose was then decided based on the responses of earlier patients by exploiting the sequential ascend and descend according to a 9: 1 biased coin design. Upon failure, the dose of remimazolam was increased by 0.025 mg/kg in the next patient. When the insertion was successful, the succeeding patient was randomized to an identical dose or a dose that was lower by 0.025 mg/kg.The ED90 of remimazolam for inhibiting responses to the insertion of a duodenoscope during ERCP was calculated. Adverse events and complications of remimazolam were recorded. RESULTS: A total of 55 elderly patients (age > 65) were included in the study. 45 successfully anesthetized patients, and 10 unsuccessfully. The ED90 of remimazolam was 0.300 mg/kg (95% CI = 0.287-0.320). ED95 was 0.315 (95% CI = 0.312-0.323) and ED99 was 0.323 (95% CI = 0.323-0.325). Among the patients, 9 patients developed hypotension, 2 patients developed bradycardia and 1 patient developed tachycardia, and hypoxia occurred in 2 patients. CONCLUSIONS: A loading dose of 0.300 mg / kg of remimazolam for elderly patients undergoing ERCP can safely, effectively, and quickly induce patients to fall asleep and inhibit responses to the insertion of a duodenoscope. TRIAL REGISTRATION: The study protocol was registered at the website ClinicalTrials.gov on 22/09/2021(NCT05053763).

Current status and prospect of anti-amyloid fibril therapy in AL amyloidosis.

Amyloid light-chain (AL) amyloidosis is a rare hematological disease that produces abnormal monoclonal immunoglobulin light chains to form amyloid fibrils that are deposited in tissues, resulting in organ damage and dysfunction. Advanced AL amyloidosis has a very poor prognosis with a high risk of early mortality. The combination of anti-plasma cell therapy and amyloid fibrils clearance is the optimal treatment strategy, which takes into account both symptoms and root causes. However, research on anti-amyloid fibrils lags far behind research on anti-plasma cells, and there is currently no approved treatment that could clear amyloid fibrils. Nevertheless, anti-amyloid fibril therapies are being actively investigated recently and have shown potential in clinical trials. In this review, we aim to outline the preclinical work and clinical efficacy of fibril-directed therapies for AL amyloidosis.

SERPINA3, FGA, AGP1, ITIH3 and SAA1 as novel biomarkers for eosinophilic granulomatosis with polyangiitis diagnosis and activity assessment.

OBJECTIVE: To identify novel biomarkers for diagnosis and prediction of active eosinophilic granulomatosis with polyangiitis (EGPA) through data-independent acquisition (DIA) analysis. METHODS: Plasma from 11 EGPA patients and 10 healthy controls (HCs) were analyzed through DIA to identify potential biomarkers. The results were validated in 32 EGPA patients, 24 disease controls (DCs), and 20 HCs using enzyme-linked immunosorbent assay (ELISA). The receiver operating characteristic (ROC) curve was used to assess the diagnostic value of candidate biomarkers. RESULTS: Thirty-five differentially expressed proteins (DEPs) (24 upregulated and 11 downregulated) were screened between EGPA and HC groups. Five proteins, including serine proteinase inhibitor A3 (SERPINA3), alpha-fibrinogen (FGA), alpha-1 acid glycoprotein 1(AGP1), inter-alpha-trypsin inhibitor heavy chain H3 (ITIH3), and serum amyloid A1 (SAA1), were significantly upregulated in EGPA compared with HCs. Apart from SAA1, all proteins were also higher in EGPA patients compared with DCs. Furthermore, a panel of SERPINA3 and SAA1 exhibited potential diagnostic value for EGPA with an area under the curve (AUC) of 0.953, while a panel of SERPINA3, FGA, AGP1, and ITIH3 showed good discriminative power to differentiate EGPA from DCs with AUC of 0.926. Moreover, SERPINA3, FGA, and AGP levels were significantly higher in active EGPA and correlated well with disease activity. A combination of SERPINA3 and AGP1 exhibited an excellent AUC of 0.918 for disease activity assessment. CONCLUSION: SERPINA3, FGA, AGP1, ITIH3 and SAA1 were identified as potential biomarkers for EGPA diagnosis and disease activity assessment. Among them, as a single biomarker, SERPINA3 has the best diagnostic performance.

A comparison of chemiluminescent immunoassay and enzyme-linked immunosorbent assay for detecting phospholipase A2 receptor antibody in primary membranous nephropathy.

Objective: The accurate detection of phospholipase A2 receptor (PLA2R) autoantibody is crucial in the diagnosis and monitoring of primary membranous nephropathy (pMN). While enzyme-linked immunosorbent assay (ELISA) is the commonly used detection method, its complexity and time-consuming nature pose challenges, especially for small sample sizes. Chemiluminescence immunoassay (CLIA) has emerged as a rapid alternative for clinical immunoassays. This study aims to compare the sensitivity, specificity, and precision of CLIA and ELISA in detecting PLA2R autoantibody. Method: A total of 145 patients with biopsy-confirmed primary membranous nephropathy and 85 patients with non-membranous nephropathy were enrolled in this comparative study. CLIA and ELISA were employed to test all samples for the presence of PLA2R autoantibodies. Statistical analysis of sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) was performed using SPSS 26.0. The diagnostic value of ELISA and CLIA for pMN was analyzed using the ROC curve, and Correlation analysis was performed using Spearman. Results: Serum levels of anti-PLA2R antibody in pMN group were significantly higher than those in nMN group(P < 0.05). The accuracy of CLIA for detecting anti-PLA2R antibody was 76.96%, while ELISA showed an accuracy of 74.78%. The sensitivity for CLIA was 64.83%, compared to 60% for ELISA. However, no statistically significant difference was observed between the two methods (P > 0.05). The overall qualitative agreement of anti-PLA2R detection was 93.35% (95% confidence interval[CI] 89.47-96.3). ROC curve analysis showed that AUC of anti-PLA2R antibody detected by ELISA and CLIA were 0.8737 (95% confidence interval [CI] 0.8270-0.9204), 0.8914 (95% confidence interval [CI]0.8495-0.9332), respectively. The Spearman correlation analysis revealed a significant correlation between them(P < 0.05). Notably, CLIA demonstrated a significant time-saving advantage, particularly when the sample size was less than 200, and especially when it was less than 20. Conclusion: CLIA and ELISA showed similar accuracy and consistency in detecting anti-PLA2R antibody for primary membranous nephropathy. However, CLIA exhibited a significant advantage in terms of automation and time-saving compared to ELISA, particularly for smaller sample sizes. This finding suggests that CLIA has the potential to become a preferred and widely adopted test in the future.

Clinical evidence of the link between gut microbiome and myalgic encephalomyelitis/chronic fatigue syndrome: a retrospective review.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a heterogeneous disorder with elusive causes, but most likely because of clinical and other biological factors. As a vital environmental factor, the gut microbiome is increasingly emphasized in various refractory diseases including ME/CFS. The present study is aimed to enhance our understanding of the relationship between the gut microbiome and ME/CFS through data analysis of various clinical studies. We conducted a literature search in four databases (PubMed, Cochrane Library, Web of Science, and Google Scholar) until May 31, 2023. Our analysis encompassed 11 clinical studies with 553 ME/CFS patients and 480 healthy controls. A comparative analysis of meta data revealed a significant decrease in α-diversity and a noticeable change in ß-diversity in the gut microbiome of ME/CFS patients compared to healthy controls. The notable ratio of Firmicutes and Bacteroides was 2.3 times decreased, and also, there was a significant reduction in the production of microbial metabolites such as acetate, butyrate, isobutyrate, and some amino acids (alanine, serine, and hypoxanthine) observed in ME/CFS patients. The lack of comparison under similar conditions with various standardized analytical methods has impeded the optimal calculation of results in ME/CFS patients and healthy controls. This review provides a comprehensive overview of the recent advancements in understanding the role of the gut microbiome in ME/CFS patients. Additionally, we have also discussed the potentials of using microbiome-related interventions and associated challenges to alleviate ME/CFS.

Epidemiological age-based differences in traumatic spinal cord injury patients: A multicenter study based on 13,334 inpatients.

CONTEXT: Compared with younger traumatic spinal cord injury (TSCI) patients, the elderly had longer delays in admission to surgery, higher proportion of incomplete injury, and longer hospital stays. However, in China, the country with the largest number of TSCI patients, there have been no large-scale reports on their age differences. OBJECTIVES: To explore the age-based differences among TSCI inpatients, focusing on the demographic and clinical characteristics, treatment status, and economic burden. METHODS: We collected the medical records of 13,334 inpatients with TSCI in the 30 hospitals of China, from January 1, 2013 to December 31, 2018. Trends are expressed as annual percentage changes (APCs) and 95% confidence intervals (CIs). RESULTS: A total of 13,334 inpatients were included. Both the number and proportion of the elderly showed an increasing trend. The APC of the number and proportion in patients ≥85 years were 39.5% (95% CI, 14.3 to 70.3; P < 0.01) and 30.5% (95% CI, 8.6 to 56.9; P < 0.01), respectively. Younger patients were more likely to undergo decompression surgery, and older patients were more likely to receive high-dose methylprednisolone sodium succinate/methylprednisolone (MPSS/MP). Of the patients ≥85 years, none underwent decompression surgery within 8 h, and only 1.4% received a high dose of MPSS/MP within 8 h after injury. Elderly patients had lower hospitalization costs than younger. The total and daily medical costs during hospitalization of patients ≥85 years were 8.06 ± 18.80 (IQR: 5.79) and 0.61 ± 0.73 (IQR: 0.55) thousands dollars, respectively. CONCLUSIONS: As the first study to focus on age differences of TSCI patients in China, this study found many differences, in demographic and clinical characteristics, treatment status, and economic costs, between older and younger TSCI patients. The number and proportion of elderly patients increased, and the rate of early surgery for elderly patients is low.

Association Between Serum 25-Hydroxyvitamin D and Trichomonas vaginalis Infection Among American Adults: NHANES 2013-2016.

BACKGROUND: Previous studies have suggested that vitamin D may possess anti-infection properties, but the relationship between vitamin D and Trichomonas vaginalis infection remains unexplored. METHODS: Using data from the National Health and Nutrition Examination Survey between 2013 and 2016, we conducted multivariate regression analyses and subgroup analyses to investigate the association between 25-hydroxyvitamin D (25[OH]D) levels and T. vaginalis infection, ensuring the robustness of our results. RESULTS: The final sample included data from 4318 individuals aged 20 to 59 years, among which 92 were diagnosed with T. vaginalis infection. For every 10 nmol/L increase in serum 25(OH)D level, there was a 22% reduction in the likelihood of T. vaginalis infection incidence (adjusted odds ratio [aOR], 0.78; 95% confidence interval [CI], 0.69-0.90). Similarly, higher concentration tertiles demonstrated relatively lower infection ratios compared with the tertile with the lowest 25(OH)D concentration (aOR, 0.54 [95% CI, 0.30-0.95; P = 0.030] for T2; aOR, 0.23 [95% CI, 0.09-0.61; P < 0.001] for T3). CONCLUSIONS: Our cross-sectional study indicates a negative association between 25(OH)D levels and the prevalence of T. vaginalis infection. However, further high-quality evidence is needed to establish a causal relationship between 25(OH)D levels and T. vaginalis infection, as well as to evaluate the potential role of vitamin D supplementation in preventing T. vaginalis infection.

AMHGCN: Adaptive multi-level hypergraph convolution network for human motion prediction.

Human motion prediction is the key technology for many real-life applications, e.g., self-driving and human-robot interaction. The recent approaches adopt the unrestricted full-connection graph representation to capture the relationships inside the human skeleton. However, there are two issues to be solved: (i) these unrestricted full-connection graph representation methods neglect the inherent dependencies across the joints of the human body; (ii) these methods represent human motions using the features extracted from a single level and thus can neither fully exploit the various connection relationships among the human body nor guarantee the human motion prediction results to be reasonable. To tackle the above issues, we propose an adaptive multi-level hypergraph convolution network (AMHGCN), which uses the adaptive multi-level hypergraph representation to capture various dependencies among the human body. Our method has four different levels of hypergraph representations, including (i) the joint-level hypergraph representation to capture inherent kinetic dependencies in the human body, (ii) the part-level hypergraph representation to exploit the kinetic characteristics at a higher level (in comparison to the joint-level) by viewing some part of the human body as an entirety, (iii) the component-level hypergraph representation to model the semantic information, and (iv) the global-level hypergraph representation to extract long-distance dependencies in the human body. In addition, to take full advantage of the knowledge carried in the training data, we propose a reverse loss (i.e., adopting the future human poses to predict the historical poses reversely) to realize data augmentation. Extensive experiments show that our proposed AMHGCN can achieve state-of-the-art performance on three benchmarks, i.e., Human3.6M, CMU-Mocap, and 3DPW.

Lactobacillus Casei-fermented Amomum Xanthioides Mitigates non-alcoholic fatty liver disease in a high-fat diet mice model.

Non-alcoholic fatty liver disease (NAFLD) is a substantial global health issue owing to its high prevalence and the lack of effective therapies. Fermentation of medicinal herbs has always been considered a feasible strategy for enhancing efficacy in treating various ailments. This study aimed to investigate the potential benefits of the Lactobacillus casei-fermented Amomum xanthioides (LAX) on NAFLD in a high-fat diet model. HFD-fed C57BL6/j mice were administered with 200 mg/kg of LAX or unfermented Amomum xanthioides (AX) or 100 mg/kg of metformin for 6 weeks from the 4th week. The 10-week HFD-induced alterations of hepatic lipid accumulation and hepatic inflammation were significantly attenuated by LAX dominantly (more than AX or metformin), which evidenced by pathohistological findings, lipid contents, inflammatory cytokines including tumor necrosis factor (TNF)-α, interleukin (IL)- 6 and IL-1ß, oxidative parameters such as reactive oxygen species (ROS) and malondialdehyde (MDA), and molecular changes reversely between lipogenic proteins such as glycerol-3-phosphate acyltransferase (GPAM) and sterol regulatory element-binding protein (SREBP)- 1, and lipolytic proteins including peroxisome proliferator-activated receptor (PPAR-α) and AMP-activated kinase (AMPK)-α in the liver tissues. In addition, the abnormal serum lipid parameters (triglyceride, total cholesterol and LDL-cholesterol) notably ameliorated by LAX. In conclusion, these findings support the potential of LAX as a promising plant-derived remedy for NAFLD.

Associations between serum per- and polyfluoroalkyl substances and thyroid hormones in Chinese adults: A nationally representative cross-sectional study.

Disruption of thyroid homeostasis has been indicated in human studies on the effects of per- and polyfluoroalkyl substances (PFASs). However, limited research exists on this topic within the general Chinese population. Based on a substantial and representative sample of the Chinese adult population, our study provides insight into how PFASs specifically affect thyroid homeostasis. The study included 10 853 participants, aged 18 years and above, sampled from nationally representative data provided by the China National Human Biomonitoring (CNHBM). Weighted multiple linear regression and restricted cubic spline (RCS) models were used to explore the associations between eight individual PFAS concentrations and total thyroxine (T4), total triiodothyronine (T3), and the T4/T3 ratio. Bayesian kernel machine regression (BKMR) and quantile-based g-computation (qgcomp) were employed to explore the joint and independent effects of PFASs on thyroid homeostasis. Both individual PFASs and PFAS mixtures exhibited a significant inverse association with serum T3 and T4 levels, and displayed a positive association with the T4/T3 ratio. Perfluoroundecanoic acid (PFUnDA) [-0.07 (95 % confidence interval (CI): -0.08, -0.05)] exhibited the largest change in T3 level. PFUnDA also exhibited a higher weight compared to other PFAS compounds in qgcomp models. Additionally, a critical exposure threshold for each PFAS was identified based on nonlinear dose-response associations; beyond these thresholds, the decreases in T3 and T4 levels plateaued. Specifically, for perfluoroheptane sulfonic acid (PFHpS) and 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), an initial decline in hormone levels was observed, followed by a slight increase when concentrations surpassed 0.7 ng/mL and 2.5 ng/mL, respectively. Sex-specific effects were more pronounced in females, and significant associations were observed predominantly in younger age groups. These insights contribute to our understanding of how PFAS compounds impact thyroid health and emphasize the need for further research and environmental management measures to address these complexities.

Impaired cerebral microvascular endothelial cells integrity due to elevated dopamine in myasthenic model.

Myasthenia gravis is an autoimmune disease characterized by pathogenic antibodies that target structures of the neuromuscular junction. However, some patients also experience autonomic dysfunction, anxiety, depression, and other neurological symptoms, suggesting the complex nature of the neurological manifestations. With the aim of explaining the symptoms related to the central nervous system, we utilized a rat model to investigate the impact of dopamine signaling in the central nervous and peripheral circulation. We adopted several screening methods, including western blot, quantitative PCR, mass spectrum technique, immunohistochemistry, immunofluorescence staining, and flow cytometry. In this study, we observed increased and activated dopamine signaling in both the central nervous system and peripheral circulation of myasthenia gravis rats. Furthermore, changes in the expression of two key molecules, Claudin5 and CD31, in endothelial cells of the blood-brain barrier were also examined in these rats. We also confirmed that dopamine incubation reduced the expression of ZO1, Claudin5, and CD31 in endothelial cells by inhibiting the Wnt/ß-catenin signaling pathway. Overall, this study provides novel evidence suggesting that pathologically elevated dopamine in both the central nervous and peripheral circulation of myasthenia gravis rats impair brain-blood barrier integrity by inhibiting junction protein expression in brain microvascular endothelial cells through the Wnt/ß-catenin pathway.

Associations between Informant-Reported Cognitive Complaint and Longitudinal Cognitive Decline in Subjective Cognitive Decline A 7-Year Longitudinal Study.

OBJECTIVE: This study aimed to determine the predictive values of informant-reported memory decline (IMD) among subjective cognitive decline (SCD) older adults from a 7-year community-based cohort study. METHOD: Ninety SCD participants were included. Demographic data and neuropsychological test scores at both baseline and 7-year follow-up were collected. Differences between SCD with IMD (+IMD) and SCD without IMD (-IMD) were compared. Logistic regression models were used to determine whether baseline IMD could predict diagnostic outcomes at 7-year follow-up. RESULTS: Forty-one percent of SCD adults had IMD. At baseline, the +IMD group showed more depressive symptoms (p = 0.016) than the -IMD group. Furthermore, the Beijing-version Montreal Cognitive Assessment (MoCA), Digit Span Test-Forward, Visual Matching and Reasoning, and Wechsler Adult Intelligence Scale-RC Picture Completion (WAIS-PC) scores in the +IMD group were significantly lower than those in the -IMD group. Fifty-four percent of +IMD participants converted to mild cognitive impairment (MCI) or dementia at follow-up, and 22.6% of the -IMD participants converted to MCI. Follow-up Mini-Mental State Examination, MoCA, and Verbal Fluency Test scores of the +IMD group were significantly lower than those in the -IMD group. The +IMD group was more likely to progress to cognitive impairment at 7-year follow-up (OR = 3.361, p = 0.028). CONCLUSIONS: SCD participants with +IMD may have poorer cognition and are more likely to convert to cognitive impairment over time. Our long-term follow-up study confirmed the importance of informants' perceptions of SCD, which can help clinicians identify individuals at risk of cognitive decline.

Immune checkpoint expression patterns on T cell subsets in light-chain amyloidosis: VISTA, PD-1, and TIGIT as potential therapeutic targets.

Amyloid light chain (AL) amyloidosis is a rare plasma cell dyscrasia with dismal prognosis. This study aims to investigate the T-cell immune checkpoint expression patterns in systemic AL amyloidosis and its relationship with clinicobiological traits. We examined the frequencies of V-domain immunoglobulin suppressor of T cell activation+ (VISTA+), programmed cell death 1+ (PD-1+), T cell immunoglobulin and mucin-domain-containing-3+ (Tim-3+), T cell immunoreceptor with Ig and ITIM domains+ (TIGIT+) T cells in peripheral blood (PB) and bone marrow (BM) from 19 patients with newly diagnosed AL amyloidosis. Patients with AL amyloidosis had significantly higher percentages of VISTA+ and PD-1+ T cells in PB than healthy individuals (HIs), with no statistical differences in BM. The percentages of some double-positive T cells in PB were also considerably higher in AL amyloidosis than those in HIs. Additionally, the patients with renal involvement had more PD-1+ and TIGIT+ T cells than the patients without, and PD-1+CD3+%, PD-1+CD4+%, PD-1+Treg% were positively correlated with 24-hour proteinuria levels. Furthermore, the AL amyloidosis patients had higher counts of PD-1+ Treg in PB than multiple myeloma (MM) patients, while the MM patients had higher counts of TIGIT+ T cells than AL amyloidosis patients. Collectively, this is the first report of elevated proportions of VISTA+ and PD-1+ T cells in PB of AL amyloidosis patients, indicating an immunosuppressive milieu, and the increased PD-1+ and TIGIT+ T cells were associated with renal damage. VISTA, PD-1, and TIGIT may be potential targets for reversing T-cell exhaustion in AL amyloidosis.

Ten-Day Vonoprazan-Amoxicillin Dual Therapy vs Standard 14-Day Bismuth-Based Quadruple Therapy for First-Line Helicobacter pylori Eradication: A Multicenter Randomized Clinical Trial.

INTRODUCTION: Whether 10-day short-course vonoprazan-amoxicillin dual therapy (VA-dual) is noninferior to the standard 14-day bismuth-based quadruple therapy (B-quadruple) against Helicobacter pylori eradication has not been determined. This trial aimed to compare the eradication rate, adverse events, and compliance of 10-day VA-dual regimen with standard 14-day B-quadruple regimen as first-line H. pylori treatment. METHODS: This prospective randomized clinical trial was performed at 3 institutions in eastern China. A total of 314 treatment-naive, H. pylori -infected patients were randomly assigned in a 1:1 ratio to either 10-day VA-dual group or 14-day B-quadruple group. Eradication success was determined by 13 C-urea breath test at least 4 weeks after treatment. Eradication rates, adverse events, and compliance were compared between groups. RESULTS: Eradication rates of VA-dual and B-quadruple groups were 86.0% and 89.2% ( P = 0.389), respectively, by intention-to-treat (ITT) analysis; 88.2% and 91.5% ( P = 0.338), respectively, by modified ITT analysis; and 90.8% and 91.3% ( P = 0.884), respectively, by per-protocol (PP) analysis. The efficacy of the VA-dual remained noninferior to B-quadruple therapy in all ITT, modified ITT, and PP analyses. The incidence of adverse events in the VA-dual group was significantly lower compared with that in the B-quadruple group ( P < 0.001). Poor compliance contributed to eradication failure in the VA-dual group ( P < 0.001), while not in the B-quadruple group ( P = 0.110). DISCUSSION: The 10-day VA-dual therapy provided satisfactory eradication rates of >90% (PP analysis) and lower rates of adverse events compared with standard 14-day B-quadruple therapy as first-line H. pylori therapy. TRAIL REGISTRATION NUMBER: ChiCTR2300070100.

Disrupted topological organization of the default mode network in mild cognitive impairment with subsyndromal depression: A graph theoretical analysis.

AIMS: Subsyndromal depression (SSD) is common in mild cognitive impairment (MCI). However, the neural mechanisms underlying MCI with SSD (MCID) are unclear. The default mode network (DMN) is associated with cognitive processes and depressive symptoms. Therefore, we aimed to explore the topological organization of the DMN in patients with MCID. METHODS: Forty-two MCID patients, 34 MCI patients without SSD (MCIND), and 36 matched healthy controls (HCs) were enrolled. The resting-state functional connectivity of the DMN of the participants was analyzed using a graph theoretical approach. Correlation analyses of network topological metrics, depressive symptoms, and cognitive function were conducted. Moreover, support vector machine (SVM) models were constructed based on topological metrics to distinguish MCID from MCIND. Finally, we used 10 repeats of 5-fold cross-validation for performance verification. RESULTS: We found that the global efficiency and nodal efficiency of the left anterior medial prefrontal cortex (aMPFC) of the MCID group were significantly lower than the MCIND group. Moreover, small-worldness and global efficiency were negatively correlated with depressive symptoms in MCID, and the nodal efficiency of the left lateral temporal cortex and left aMPFC was positively correlated with cognitive function in MCID. In cross-validation, the SVM model had an accuracy of 0.83 [95% CI 0.79-0.87], a sensitivity of 0.88 [95% CI 0.86-0.90], a specificity of 0.75 [95% CI 0.72-0.78] and an area under the curve of 0.88 [95% CI 0.85-0.91]. CONCLUSIONS: The coexistence of MCI and SSD was associated with the greatest disrupted topological organization of the DMN. The network topological metrics could identify MCID and serve as biomarkers of different clinical phenotypic presentations of MCI.

Low-frequency variability in theta activity modulates the attention-fluctuation across task and resting states.

Sustained attention is not constant but fluctuates influencing our task performance. Albeit intensive investigations, it remains unclear whether the attention-fluctuation during tasks is derived from its spontaneous fluctuation in the resting state. Here, we addressed this issue by investigating the attention-fluctuation in both task and resting states, through the EEG measurement of theta-variability. We found significant rest-task modulation of theta-variability, i.e., reduced theta-variability in the task state compared to the resting state. This task and rest modulation was manifested in the low-frequency of theta-variability (<0.1 Hz). Furthermore, the low-frequency theta-variability exhibited a significant rest-task correlation, however, only the low-frequency theta-variability in the task state but not in the resting state was correlated with the behavioral performance. These findings shed light on the low-frequency feature of attention-fluctuation, and advanced our understanding of sustained attention by suggesting that the theta-variability in low-frequencies was relevant to attention level in task state.