Dietary lipids are essential for brain health. However, high-fat diets (HFD) have produced conflicting results in studies on aging brain health, likely due to variations in fatty acid composition. While aging-related glial lipid accumulation is exacerbated by saturated fatty acids (SFAs)-rich HFD, it remains unclear whether replacing SFAs with n-3 polyunsaturated fatty acids (PUFAs) can mitigate this effect and the associated neuroinflammation. This study investigates the effects of SFAs-rich and n-3 PUFAs-rich HFDs in 18-month-old C57BL/6J mice over a 12-week period. Mice fed the SFAs-rich HFD showed increased body weight, elevated glucose and lipid levels, and lipid accumulation in glial cells. Behavioral tests, including novel object recognition and the Barnes maze, revealed significant cognitive impairments in these mice. In contrast, the n-3 PUFAs-rich HFD increased brain docosahexaenoic acid levels, activated the ATP-binding cassette transporter A1/apolipoprotein E pathway, reduced lipid accumulation in glial cells, and ultimately reversed cognitive decline. Consistent with these findings, the n-3 PUFAs-rich diet also attenuated inflammatory markers such as tumor necrosis factor α and interleukin 1β, and decreased oxidative stress markers including malondialdehyde and oxidized glutathione/reduced glutathione. These findings provide novel insights into the role of fatty acid composition in HFD affecting aged brain health, offering strong evidence for the neuroprotective benefits of n-3 PUFAs-enriched diets.
This report describes a rare case of neuromyelitis optica spectrum disorder (NMOSD) complicated by systemic capillary leak syndrome (SCLS) and reviews the literature to examine the clinical features, pathogenesis, and therapeutic implications of autoimmune disease–associated SCLS. A 20-year-old woman with NMOSD developed sudden-onset SCLS, presenting with hypotension, hemoconcentration (hematocrit 58.7%), hypoalbuminemia (26 g/L), and pulmonary edema after initial immunotherapy. Cardiogenic and septic shock, as well as pulmonary embolism, were excluded, leading to a diagnosis of SCLS. Intensive treatment with albumin replacement, thoracic drainage, and intravenous immunoglobulin (IVIG, 0.4 g/kg/day) stabilized her condition. Maintenance therapy with satralizumab, an anti–interleukin-6 receptor monoclonal antibody, achieved sustained remission over 1 year. A review of 12 cases (including this case) identified autoimmune diseases—most commonly Sjögren’s syndrome (41.7%) and NMOSD (16.7%)—as frequent SCLS comorbidities. Infections (33.3%) and autoimmune flares (25%) were the most common triggers. Multimodal therapy combining glucocorticoids and IVIG, with or without additional immunosuppressants, resulted in clinical improvement in 75% of cases. This report emphasizes that SCLS is a life-threatening complication of autoimmune diseases, particularly NMOSD. Autoimmune disease relapses and infections are common precipitating factors. Prompt diagnosis and intervention are critical. Satralizumab warrants further investigation as a potential therapeutic option for this rare comorbidity.
Intermittent fasting (IF) offers a potential strategy to counteract Alzheimer’s disease (AD) progression. In our 16-week study on AD transgenic mice, IF positively affected cognitive function and reduced amyloid-β (Aβ) accumulation, verifying the IF’s role in modulating neuroinflammation. Multiomics integration revealed strong links between IF-induced hippocampal gene expression, gut microbiota, and serum metabolites beneficial for cognition. Indole-3-propionic acid (IPA) emerged as a pivotal microbial metabolite. Blocking its neuronal receptor, pregnane X receptor (PXR), abolished IF’s effects. Human data paralleled these findings, showing lower IPA levels in patients with mild cognitive impairment and AD than in controls. IPA supplementation and IPA-producing Clostridium sporogenes reproduced IF’s cognitive benefits, whereas PXR blockade in neurons or disruption of IPA synthesis abrogated them. IPA crossed the blood-brain barrier, exhibited potent anti-inflammatory activity, and suppressed Aβ accumulation, essential for neuroprotection. These results underscore microbial metabolites regulated by IF, particularly IPA, as therapeutic candidates for AD, highlighting the critical role of the gut-brain axis in neurodegeneration.
INTRODUCTION:With the global ageing population accelerating, the prevalence of Alzheimer's disease (AD) continues to rise annually. However, the underlying mechanisms of AD remain unclear, and effective treatments are still lacking. Apolipoprotein E (ApoE) gene polymorphism and dietary habits are critical risk factors for AD. Time-restricted feeding (TRF), an intermittent fasting strategy that limits the daily window of food intake while maintaining nutritional balance, has garnered significant attention in recent years for its potential to improve cognitive dysfunction. This study aims to investigate the effect of TRF on cognitive improvement in AD patients within the context of genetic background and to explore the role of ApoE polymorphism in these mechanisms. METHODS AND ANALYSIS:This single-centre, prospective, randomised, open-label, blinded-endpoint trial will recruit 160 patients with mild to moderate cognitive impairment due to AD from Peking University Shenzhen Hospital. Participants will be stratified based on ApoE genotype into ApoE4 non-carriers and ApoE4 carriers, then randomly assigned to either a TRF intervention group or a normal control group for a 24-month intervention period. The primary outcomes are changes in the Minimum Mental State Examination scale score, Montreal Cognitive Assessment scale score and Clinical Dementia Rating-Sum of Boxes scale score. Key secondary outcomes include the Activities of Daily Living scale score, blood AD biomarkers, lipid levels, ketone body levels and cerebral glutamate levels. Follow-up assessments will be conducted at baseline, 6, 12, 18 and 24 months. ETHICS AND DISSEMINATION:Ethical approval for this study was obtained from the Research Ethics Committee of Peking University Shenzhen Hospital (Ethics No. 2024-151). Written informed consent will be obtained from all participants before the commencement of the trial. The findings will be disseminated through peer-reviewed publications. TRIAL REGISTRATION NUMBER:ChiCTR2400092653.
Abstract(1)BackgroundRecent studies suggest a potential link between gut microbiomes (GMs) and inflammatory diseases, but the role of GMs in lichen sclerosus (LS) remains unclear. This study aims to investigate the causal relationship between GMs and LS, focusing on key GM taxa.(2)MethodsWe utilized GWAS summary statistics for 211 GM taxa and their association with 2,445 LS patients and 353,088 healthy controls, employing Mendelian randomization (MR). GWAS data for GM taxa came from the MiBioGen consortium, and for LS from the FinnGen consortium. The primary analytical tools included the inverse-variance weighted (IVW) method, weighted MR, simple mode, weighted median, and MR-Egger methods. Sensitivity analyses included leave-one-out analysis, MR-Egger intercept test, MR-PRESSO global test, and Cochrane’s Q-test. A reverse MR analysis was conducted on bacteria identified in the forward MR study.(3)ResultsWe identified one strong causal relationship: orderBurkholderiales[odds ratio (OR) = 0.420, 95% confidence interval (CI): 0.230 - 0.765, p = 0.005], and three nominally significant relationships: phylumCyanobacteria(OR = 0.585, 95% CI: 0.373 - 0.919, p = 0.020), classBetaproteobacteria(OR = 0.403, 95% CI: 0.189 - 0.857, p = 0.018), and genusButyrivibrio(OR = 0.678, 95% CI: 0.507 - 0.907, p = 0.009). Moreover, this MR analysis was not impacted by horizontal pleiotropy, according to the MR-Egger intercept test and MR-PRESSO global test (p > 0.05). Remarkably, the reliability of our results was confirmed by leave-one-out analysis. Reverse MR analysis showed no significant causal relationship between LS and GM.(4)ConclusionsThis MR study identifies specific gut flora linked to a lower risk of LS, offering new insights for disease treatment and prevention. Future research should incorporate metagenomics sequencing of extensive microbiome GWAS datasets.
Background Despite previously reported correlations between intracranial arterial calcification (IAC) and white matter hyperintensities (WMH), little is known about the relationship between IAC pattern and WMH. By differentiating intimal and medical IAC, we aimed to investigate the relationship between IAC pattern and WMH. Methods Consecutive patients with acute ischemic stroke were included. IAC pattern was categorized as intimal or medial on plain brain CT. The number of cerebral arteries involved by IAC for each patient was recorded. IAC severity of each artery was defined as focal or diffuse. On brain MRI, the burden of WMH was graded on a visual rating scale and classified as absent mild, moderate and severe. Multiple logistic regression was performed to examine the relationship between IAC and WMH. Results Among 265 recruited patients, intimal IAC was detected in 54.7% patients, medial IAC in 48.5% patients and coexistent (intimal and medial) IAC in 52.1% patients. Diffuse IAC was in 27.9% patients, all of which were medial IACs. WMH was found in 75.5% patients, including 105 patients (39.6%) with mild WMH, 69 (26.0%) with moderate WMH and 26 (9.8%) with severe WMH. The presence and severity of medial IAC were correlated with WMH occurrence ( p <0.001, respectively). Chi-square linear trend suggested the number of arteries involved by medial IAC ( p <0.001) and the severity of medial IAC ( p <0.001) were correlated with WMH burden. After adjusting age, hypertension, history of stroke and history of ischemic heart disease, multiple ordinal regression demonstrated a positive correlation between the number of arteries involved by medial IAC ( p <0.001) and the severity of medial IAC ( p <0.001) with the overall burden of WMH. Conclusions Medial IAC was correlated with the burden of WMH. The dose-effect relationship between IAC and WMH suggests the need of further investigations on shared underlying mechanisms of intracranial large artery disease and cerebral small vessel disease.
Gynecologic cancers are one of the main health concerns of women throughout the world, and the early diagnosis and effective therapy of gynecologic cancers will be particularly important for the survival of female patients. As a current hotspot, carbon nanomaterials have attracted tremendous interest in tumor theranostics, and their application in gynecologic cancers has also been developed rapidly with great achievements in recent years. This Overview Article summarizes the latest progress in the application of diverse carbon nanomaterials (e.g., graphenes, carbon nanotubes, mesoporous carbon, carbon dots, etc.) and their derivatives in the sensing, imaging, drug delivery, and therapy of different gynecologic cancers. Important research contributions are highlighted in terms of the relationships among the fabrication strategies, architectural features, and action mechanisms for the diagnosis and therapy of gynecologic cancers. The current challenges and future strategies are discussed from the viewpoint of the real clinical application of carbon-based nanomedicines in gynecologic cancers. It is anticipated that this review will attract more attention toward the development and application of carbon nanomaterials for the theranostics of gynecologic cancers.
目的:本研究探讨高通量血液透析对维持性血液透析患者并发症的影响.方法:以多中心、开放、自身对照方法评价高通量透析对维持性血液透析患者的影响.结果:Revaclear高通量血液透析器在毒素清除、血压改善、透析充分性、血液改善、精神状况方面优于低通量血液透析器.结论:高通量血液透析是目前常规血液透析的发展方向.百特Revaclear高通量透析器能够减少维持性血液透析患者的并发症,提高患者的生存质量.
目的 分析血透过程中出现的不安全因素,探讨相应对策.方法 结合我院血透实际情况,对护理过程中出现的一些不安全因素进行总结,同时分析原因并提出相应的对策.结果 血透过程中存在的不安全因素有空气栓塞、低血压、出血、心力衰竭等,对此采取相应的护理措施,提高护理质量.结论 针对血透过程中存在的不安全因素采取有效管理和防范措施,可以提高医疗质量.
Polymorphisms of DNA repair enzymes which may influence their repair efficiency lead to diseases, for example, senile cataract. In this study, we aimed to analyze the association of single nucleotide polymorphisms in AP endonuclease-1 (APE1), 8-oxoguanine glycosylase-1 (OGG1) and X-ray repair cross-complementing-1 (XRCC1) genes with the risk of age-related cataract in a Chinese population. Genotyping was carried out by the polymerase chain reaction and DNA sequencing on 402 cataract patients and 813 controls in this study. Differences in the frequencies were estimated by the chi-square test, and risk was estimated using unconditional logistic regression after adjusting for age and gender. Our results demonstrated there was a significant difference between the case and control groups in the APE1-141 G/G genotype (P=0.002). This difference still existed after adjusting for age and gender (P*=0.003). The APE1-141 T/T genotype and T allele frequencies were significantly higher in cataract patients, while the G/G genotype and G allele frequencies in patients were significantly lower than in controls (P < 0.05). The APE1-141 G/G genotype (OR, 0.49; 95% CI, 0.31-0.77) seems to have a protective role against cataract, and the T allele seems to have a deleterious role in the development of cataract. In OGG1 Ser326Cys and XRCC1 Arg399Gln polymorphisms, there were no significant differences in frequencies of the variant homozygous in patients compared with controls.
OBJECTIVE:To assess the blood coagulation function and investigate the appropriate dose of unfractionated heparin by thromboelastograph in maintenance hemodialysis (MHD) patients.METHODS:Thirty MHD patients were enrolled in this study and divided into two groups. The total dose of unfractionated heparin was below 80 u/kg in the low-dose group (LH, n=16), while it exceeded 80 u/kg in the high-dose group (HH, n=14). Blood routine tests and conventional coagulation examinations were measured before hemodialysis. TEG and activated partial thromboplastin time (APTT) were examined at the beginning and the end of hemodialysis at the arterial circuit, and the second hour (h 2) at the venous circuit.RESULTS:The initial bolus dose of unfractionated heparin for LH and HH groups were (26.6±6.2) u/kg vs. (42.3±8.2) u/kg and the repeated maintenance dose for both the groups were (13.7±5.1) u/kg/h vs. (18.2±4.3) u/kg/h. No significant difference was noticed in results from blood routine tests and conventional coagulation parameters between the two groups. In LH group, the increase of APTT at h 2 of hemodialysis was significant compared with the baseline, while it recovered partly at the end of hemodialysis. R value prolonged at h 2 and the end of hemodialysis. CI value was more negative at the end of hemodialysis. In HH group, APTT obviously prolonged at h 2 and the end of hemodialysis. R value also obviously prolonged at h 2 of hemodialysis. At the end of hemodialysis, R and K values prolonged, MA value reduced, and CI value was more negative. APTT was significantly different between the two groups at h 2 of hemodialysis. At the end of hemodialysis, APTT was still extended in HH group, but there was no significant difference. R value at h 2, and R, K, MA, CI values at the end of hemodialysis were significantly different between the two groups. R values at the end of hemodialysis had a direct correlation with the dose of unfractionated heparin (r=0.403, P=0.041), but APTT had not. There was no significant difference in transmembrane pressure, venous pressure and filter clotting between the two groups.CONCLUSION:Low-dose heparin is effective and safe as anticoagulant in hemodialysis. TEG shows that the blood coagulation function is more sensitive than conventional coagulation parameters and is useful to anticoagulant therapy in MHD patients.
Recent studies suggest that the ability to form and grow tumors specifically resides in a small cell population called cancer stem cells (CSCs). These studies were conducted mainly on various human cancers; however, isolation and characterization of stem cells from cholangiocarcinoma have not been attempted. The molecular markers CD24, CD44, CD34, and epithelial cell adhesion molecule (EpCAM) are widely used, individually or in combination, to characterize some types of CSCs. In this study, we used these markers to identify a subpopulation of cells in extrahepatic cholangiocarcinoma (ECC) with cancer stem/progenitor cell‐like properties. We found that CD24 + CD44 + EpCAM high cells (0.39–2.27%) were present in human ECC tissues. The expression of a CD24 + CD44 + EpCAM high subpopulation was consistent with primary cancers and could be duplicated during serial in vivo passaging in NOD/SCID mice. CD24 + CD44 + EpCAM high cells isolated from 3 cholangiocarcinoma xenografts showed high tumorigenic potential compared with CD24 − CD44 − EpCAM low/− cells. These tumorigenic ECC cells exhibited the stem cell properties of self‐renewal and ability to produce heterogeneous progeny. We report the identification of a CSC population in ECC characterized by CD24, CD44 and EpCAM phenotypes. Our findings could provide new insight into the tumorigenesis of cholangiocarcinoma and offer a potential target for anti‐cancer therapy.
Background Moxibustion, acupuncture and other acupoint stimulations are commonly used for the correction of breech presentation. This systematic review aims to evaluate the efficacy and safety of moxibustion and other acupoint stimulations to treat breech presentation. Methods We included randomized controlled trials (RCTs) and controlled clinical trials (CCTs) on moxibustion, acupuncture or any other acupoint stimulating methods for breech presentation in pregnant women. All searches in PubMed, the Cochrane Library (2008 Issue 2), China National Knowledge Information (CNKI), Chinese Scientific Journal Database (VIP) and WanFang Database ended in July 2008. Two authors extracted and analyzed the data independently. Results Ten RCTs involving 2090 participants and seven CCTs involving 1409 participants were included in the present study. Meta-analysis showed significant differences between moxibustion and no treatment (RR 1.35, 95% CI 1.20 to 1.51; 3 RCTs). Comparison between moxibustion and knee-chest position did not show significant differences (RR 1.30, 95% CI 0.95 to 1.79; 3 RCTs). Moxibustion plus other therapeutic methods showed significant beneficial effects (RR 1.36, 95% CI 1.21 to 1.54; 2 RCTs). Laser stimulation was more effective than assuming the knee-chest position plus pelvis rotating. Moxibustion was more effective than no treatment (RR 1.29, 95% CI 1.17 to 1.42; 2 CCTs) but was not more effective than the knee-chest position treatment (RR 1.22, 95% CI 1.11 to 1.34; 2 CCTs). Laser stimulation at Zhiyin (BL67) was more effective than the knee-chest position treatment (RR 1.30, 95% CI 1.10 to 1.54; 2 CCTs,). Conclusion Moxibustion, acupuncture and laser acupoint stimulation tend to be effective in the correction of breech presentation.
Objective: To probe the effect of mastoscopic in modified radical mastectomy operation for preserving nipple-areolar complex in the treatment of breast cancer. Methods: Thirty patients, with breast cancer of a diameter≤3 cm and a distance≥3 cm from the mammary areola were treated by mastoscopic from November 2003 to August 2006. After the lipoly- sis and suction of axillary fat, mastoscopic axillary lymph node dissection was performed. Results: The average operation time was 128.9 min (120–156 min), the intraoperative blood loss was 56 mL (30–100 mL). The mean lymph nodes harvested by endoscopy were 16 (6–34). Excellent cosmetic outcomes were obtained with symmetrical breast development and all the patients were satisfied with the treatment. Postoperative follow-up for 2–29 months (mean, 16.6 months) found no local recur-rence. Conclusion:This model of operation can protect the upper limb function and has value of aesthetics of the brisket. What’s more, improve the quality of survive of the patients.
To investigate whether the side population cells (SP cells) exist in human gallbladder carcinoma cell line and the differences of drug resistance gene ABCG2 expression in SP cells, non-SP cells and GBC-SD cell lines.