The value of cholinesterase inhibitors for improving neuropsychiatric and functional assessment scores in patients with alzheimer disease: a systematic review and meta-analysis of on placebo-controlled RCTs.

INTRODUCTION: At present, increasing reports from different aspects indicated that cholinesterase inhibitors (ChEIs) may be effective on improving neuropsychiatric and functional assessment scores in patients with Alzheimer disease (AD). However, no studies comprehensively and detailedly evaluated the effect of ChEIs on AD. The present analysis was designed to comprehensively evaluate the efficacy and safety of ChEIs for AD. METHODS: Two independent researchers systematically reviewed 1096 searching records in PubMed, Embase, Cochrane Library and Web of Science from inception to May 10, 2023, and finally identified 12 randomized, double-blind, placebo-controlled trials with 6908 participants according to predetermined inclusion and exclusion criteria. The effects were assessed with standardized mean difference (SMD) or odds ratio (OR). The primary outcomes were the mean change and least squares (LS) mean change from baseline to endpoint of neuropsychiatric and functional assessment scores. The secondary outcome was adverse events of ChEIs when compared to placebo for patients with AD. All statistical analyses were performed using the standard statistical procedures provided in Review Manager 5.2 and and Stata 12.0. RESULTS: Pooled analysis indicated that ChEIs significantly improved the assessment scores of the AD Assessment Scale (ADAS) (SMD -1.57; 95% CI -2.64 to -0.51), Clinician's Interview-Based Impression of Change-Plus caregiver input (CIBIC-Plus) (SMD -0.28; 95% CI -0.41 to -0.15), the Neuropsychiatric Inventory (NPI) (both SMD -1.67; 95% CI -2.88 to -0.47 for 10-tiem total score and SMD -1.83; 95% CI -3.25 to -0.42 for 12-tiem total score), and the AD Cooperative Study-Activities of Daily Living (ADCS-ADL) total score (SMD 2.44; 95% CI 1.29 to 3.59), evaluated with mean change from baseline to endpoint. In addition, when evaluated with the LS mean change from baseline to endpoint, ChEIs significantly improved Mini-Mental State Examination (MMSE) total score, the Clinician Interview-Based Impression of Severity, CIBIC-Plus, ADCS-ADL total score, NPI, ADAS. Regarding to adverse events (AEs) of patients with AD, it indicated that compared to placebo, ChEIs did not increase the frequency of severe and serious AEs (fatal or nonfatal) as well as the incidence of death. CONCLUSIONS: Our analysis indicated that ChEIs treatment generally improved neuropsychiatric and functional assessment scores in patients with AD though opposite result was observed in Wechsler Memory Scale. ChEIs had an acceptable safety profile in patients with AD without increasing of any crucial adverse or outcomes.

Lower serum insulin-like growth factor-1 levels are independently associated with anemia in patients undergoing maintenance hemodialysis.

The relationship between serum insulin-like growth factor-1 (IGF-1) levels and anemia in patients undergoing maintenance hemodialysis (MHD) remains unclear. This cross-sectional study included patients who underwent MHD treatment for >3 months at our dialysis center in March 2021. Demographic and clinical data were recorded. Blood samples were collected before the hemodialysis sessions, and general serum biochemical parameters, routine blood markers, and serum IGF-1 levels were measured. Patients were divided into a group without anemia (hemoglobin ≥110 g/L) and a group with anemia (hemoglobin <110 g/L), and multivariable linear and binary logistic regression analyses were performed to study the relationship between the levels of serum IGF-1 and anemia. A total of 165 patients (male/female = 99:66) with MHD were enrolled in the study, with a median age of 66.0 (58.0, 75.0) years and a median dialysis vintage of 27.0 (12.0, 55.0) months. The mean hemoglobin level was 96.38 ± 16.72 g/L, and 126 patients had anemia (76.4%). Compared to patients without anemia, patients with anemia had lower serum IGF-1 and triglyceride levels and higher intravenous iron supplementation on dialysis (all p < 0.05). After adjusting for confounding factors in different models, the nine-model multivariate binary logistic regression analyses also confirmed that lower serum IGF-1 levels and serum IGF-1 < 197.03 ng/ml were both independently associated with anemia in patients undergoing MHD. However, further multicenter studies with larger sample sizes are required to confirm these findings.

TMAO promotes dementia progression by mediating the PI3K/Akt/mTOR pathway.

BACKGROUND: Dementia poses a serious threat to the daily and social abilities of patients, and trimethylamine-N-oxide (TMAO) is a metabolite of the gut microbiota involved in regulating the inflammatory response. However, the role of TMAO in dementia needs further investigation. This study aimed to investigate the effects and possible mechanisms of TMAO on dementia, which may provide ideas for the treatment of dementia. MATERIALS AND METHODS: Dementia mice were induced by D-galactose + AlCl3, and the changes in learning memory capacity, histopathology, inflammatory factors, and PI3K/Akt/mTOR in mice treated with TMAO were analyzed to determine the mechanism of TMAO action on dementia. In addition, the effect of TMAO+PI3K inhibitor treatment on mice was also analyzed to further determine the mechanism of TMAO effect on dementia. RESULTS: The results revealed that the dementia group had significantly higher TMAO levels and a significant hippocampal injury and inflammatory response. TMAO treatment promoted hippocampal injury and promoted the level of inflammatory cytokines. Further study of PI3K/Akt/mTOR signaling pathway showed that the expression of p-PI3K, p-Akt, and p-mTOR was significantly increased in the dementia group, and it was more obvious after TMAO treatment. And hippocampal injury, inflammatory response, and increase of p-PI3K, p-Akt, p-mTOR were reversed by TMAO+PI3K inhibitor. CONCLUSIONS: This study determined that TMAO promotes dementia through the PI3K/Akt/mTOR signaling pathway, suggesting that TMAO may be a potential target for dementia.

Analysis of risk factors for the development of cognitive dysfunction in patients with cerebral small vessel disease and the construction of a predictive model.

Background: Cognitive dysfunction in cerebral small vessel disease (CSVD) is a common cause of vascular dementia. The purpose of this study was to find independent risk factors for the development of cognitive dysfunction in patients with CSVD and establish a risk prediction model, in order to provide a reference for clinical diagnosis and treatment of such patients. Methods: In this study, clinical data of patients with CSVD admitted to the Department of Neurology in Gansu Provincial Hospital from December 2019 to December 2021 were collected, and 159 patients were finally included after strict screening according to the inclusion and exclusion criteria. There were 43 patients with normal function and 116 patients with cerebral small vessel disease cognitive impairment (CSVDCI). The logistic multivariable regression model was used to screen out the independent risk factors of cognitive dysfunction in patients with CSVD, and the nomogram of cognitive dysfunction in patients with CSVD was constructed based on the results of the logistic multivariable regression analysis. Finally, the accuracy of the prediction model was evaluated by C-index, calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). Results: The results of multivariable logistic regression analysis showed that hypertension (OR = 2.683, 95% CI 1.119-6.432, P = 0.027), homocysteine (Hcy) (OR = 1.083, 95% CI 1.026-1.143, P = 0.004), total CSVD MRI Score (OR = 1.593, 95% CI 1.025-2.475, P = 0.039) and years of schooling (OR = 0.883, 95% CI 0.798-0.978, P = 0.017) were independent risk factors for the development of cognitive dysfunction in patients with CSVD. The C-index of this prediction model was 0.806 (95% CI 0.735-0.877), and the calibration curve, ROC curve, and DCA curve all showed good predictive power in the nomogram. Conclusions: The nomogram constructed in this study has high accuracy and clinical utility in predicting the occurrence of cognitive dysfunction in patients with CSVD. For patients with CSVD with the above risk factors, active clinical intervention and prevention are required during clinical consultation and disease management to avoid cognitive impairment as much as possible.

Complete mitochondrial genome of Chironomus nipponensis, new record from China (Diptera: Chironomidae).

The complete mitochondrial genome of Chironomus nipponensis Tokunaga, 1936 was sequenced and assembled from the whole genome data. The mitochondrial genome length was 16184 bp and contained 22 transfer RNA genes, 13 protein-coding genes, 2 ribosomal RNA genes, and 1 D-loop control region. Phylogenetic and taxonomic analysis based on the concatenated nucleotide sequences of 37 genes from 14 related species was reconstructed. The phylogeny revealed that C. nipponensis is closely related to three other Chironomus species, which is consistent with the traditional morphological studies.

Etiologic Spectrum of Intestinal Obstruction in Ningxia District: A Retrospective Analysis of 4908 Cases in a 10-Year Period.

BACKGROUND: Economic disparity contributes to the variation of intestinal obstruction (IO) etiologic spectrum. Clarifying the etiology distribution in local regions can help to unravel IO and promote early diagnosis, henceforth making sure standardized therapeutic interventions. METHODS: Medical data of 4908 inpatients diagnosed with IO admitted to the General Hospital of Ningxia Medical University between January 2004 and December 2013 were recruited and analyzed retrospectively. The associated profiles included demographic features, clinical manifestations, and previous therapeutic operations. RESULTS: 4908 cases of intestinal obstruction were identified during the period of study. It denoted that the hospitalization rate of IO has maintained upward momentum; the top four causes of IO were adhesion, tumor, intussusception, and hernias. These covered up nearly 80% of the total constitution. Among them, adhesive intestinal obstruction accounted for 45.17%, malignant bowel obstruction for 21.09%, intussusception for 8.72%, and hernia for 4.73%; abdominal surgery constituted for the majority (78.62%) of adhesive obstruction. The followed up analysis also found that appendectomy accounted for the biggest percentage, 28% of operation cases. Malignant bowel obstruction can have a rate of 96.43% in 1035 cases led by tumor lesions. Of which, the primary intestinal malignant tumor accounted for 68.64% and metastatic tumors for 31.36%. Nearly 50% occurred in the large intestine. The overall mortality of all 4908 cases was 4.7%. CONCLUSION: The hospitalizations of IO delineated an increasing trend. Adhesion was the main etiology in IO. The odds of malignant bowel obstruction was increasing in the proportion of IO. There were some differences towards the etiologic spectrum compared with western countries.

Effectiveness of rituximab in neuromyelitis optica: a meta-analysis.

BACKGROUND: Neuromyelitis optica (NMO) is a severe inflammatory autoimmune disorder of the central nervous system and often results in paralysis or blindness. Rituximab (RTX) is a mouse-human chimeric monoclonal antibody specific for the CD20 antigen on B lymphocytes and used to treat many autoimmune diseases. Disability and relapses were measured using the Expanded Disability Status Scale (EDSS) and annualized relapse rate (ARR) ratio to evaluate the effectiveness of RTX. This review performed a meta-analysis of the efficacy of RTX in NMO. METHODS: We searched through the databases of PubMed, Embase, and Cochrane Library. We compiled 26 studies, in which 18 used ARR ratio, 22 used EDSS score, and 14 used both variables. Differences in the ARR ratio and EDSS score before and after RTX therapy were used as the main efficacy measures. Publication bias was evaluated after the consistency test, and a sensitivity analysis was performed with mean difference (MD) of the efficacy of RTX. RESULTS: A meta-analysis of 26 studies with 577 participants was conducted. Antibodies against aquaporin-4 autoantibody were recorded in 435 of 577 (75.39%) patients with NMO. RTX therapy resulted in a mean (WMD) - 1.56 (95% CI, - 1.82 to - 1.29) reduction in the mean ARR ratio and a mean (WMD) - 1.16 (95% CI, - 1.36 to - 0.96) reduction in the mean EDSS score. A total of 330 of 528 patients (62.9%) reached the relapse-free state. A total of 95 of 577 (16.46%) patients had adverse reactions. CONCLUSIONS: RTX has acceptable tolerance, reduces the relapse frequency, and improves disability in most patients with NMO. Future studies should focus on reducing the health-care costs, improving the functional outcomes, and reducing the adverse effects associated with RTX treatment.

Long Noncoding RNA EBF3-AS Promotes Neuron Apoptosis in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common form of dementia; its pathophysiological mechanism remains unclear. Long noncoding RNAs (lncRNAs) play key roles in AD. lncRNA EBF3-AS has been found dysregulated in AD, which is abundantly expressed in the brain. The aim of this study was to investigate the role of EBF3-AS in AD. Results showed that the expressions of lncRNA EBF3-AS and EBF3 (early B cell factor 3) were upregulated in hippocampus of APP/PS1 mice (AD model mice). EBF3-AS knockdown by siRNA inhibited the apoptosis induced by Aß25-35 and okadaic acid (OA) in SH-SY5Y. The expression of EBF3 was downregulated in Aß25-35- and OA-treated SH-SY5Y, which was reversed by EBF3-AS knockdown. EBF3 knockdown can reverse the Aß25-35-induced apoptosis in SH-SY5Y. These results revealed that lncRNA EBF3-AS promoted neuron apoptosis in AD, and involved in regulating EBF3 expression. EBF3-AS may be a new therapeutic target for treatment of AD.

Increasing rate of inflammatory bowel disease: a 12-year retrospective study in NingXia, China.

BACKGROUND: In China, the incidence of Inflammatory bowel disease (IBD) has shown a significant growth trend. Analysis of the epidemiology, clinical manifestations, diagnostic means, and treatment of IBD will further improve the clinician's understanding of IBD, improve knowledge and further enable early diagnosis and standardized therapeutic management. The purpose of this study was to analyze the clinical characteristics of IBD inpatients in General Hospital of NingXia Medical University over a 12-year period to identify trends in clinical and epidemiological features, clinical manifestations, and treatment programs. METHODS: By excluding188 patients with incomplete information or incompatible with the 2012 Guidlines cases, we retrospectively analyzed the case records of 567 inpatients with a diagnosis of IBD admitted to the General Hospital of NingXia Medical University between January 2002 and December 2014. The clinical epidemiological features, clinical manifestations, diagnostic methods, and therapeutic status were analyzed. RESULTS: Over the study period, IBD hospitalization rates in 2002 and 2014 groups was 1.96 % and 4.05 %, increased 2.07 times. Of 567 cases of IBD, 483 (85.19 %) cases were categorized as ulcerative colitis (UC) and 84 as Crohn's disease (CD) (14.81 %). Total male cases were 321 (56.61 %). Mean age of cases was 49.06 ± 14.92 years for UC and 44.84 ± 14.67 years for CD. The majority of UC was located in the colon, with a moderate level of disease activity. A combination of clinical manifestations and colonoscopy was mostly used to make a diagnosis; relatively the rate of pathological diagnosis was low, with a small proportion of patient's diagnosed based on radiology. Treatment with SASP/5ASA and steroids was applied to the majority of inpatients and 47.83 % were treated with antibiotics; in contrast, only 1.86 % cases were treated with immunosuppressive therapy. CONCLUSIONS: An increasing trend of admissions for IBD can be observed in our study; there are some differences in clinical features and treatment compared with Western countries, and further research into this is required.