Objective To investigate the relationship between food patterns and mild cognitive impairment (MCI) among Chinese elderly to provide evidence for risk prevention and control of MCI among elderly ...population. Methods Between February 2017 to October 2018, a stratified multistage cluster sampling method was used to select participants from 760 communities of six districts in Xi'an, China, for 49-item food frequency questionnaire survey. A total of 2311 participants aged 60 to 88 years were included in the study with 444 (19.2%) participants of MCI among Chinese community-dwelling elderly adults. Food patterns associated with risk of dementia were assessed by using a reduced rank regression (RRR) analysis, and the multivariate linear regression was used to test trends of risk factors across scores for the food pattern. Results Four dietary patterns were extracted which explained 88.65% of the total variation in food intakes. Furthermore, the food pattern 1 (FP1) accounted for 60.25% of the total variation of all responsible variables and as a target dietary pattern in the study, which was related with high intake of legumes, vegetables, fruits, milk and dairy products, nuts and a low intake of noodles and cereals (p0.05). Multivariate linear regression analysis showed that participants with a high score for FP1 had higher direction, memory and language function and FP1 can improve the ability of cognitive function (p0.05). Conclusion The FP1 of Chinese dietary patterns was significantly correlated with higher cognitive function which can reduce the risk of MCI among Chinese elderly.
Survivors of sepsis may encounter cognitive impairment following their recovery from critical condition. At present, there is no standardized treatment for addressing sepsis-associated ...encephalopathy.
GG (LGG) is a prevalent bacterium found in the gut microbiota and is an active component of probiotic supplements. LGG has demonstrated to be associated with cognitive improvement. This study explored whether LGG administration prior to and following induced sepsis could ameliorate cognitive deficits, and explored potential mechanisms.
Female C57BL/6 mice were randomly divided into three groups: sham surgery, cecal ligation and puncture (CLP), and CLP+LGG. Cognitive behavior was assessed longitudinally at 7-9d, 14-16d, and 21-23d after surgery using an open field test and novel object recognition test. The impact of LGG treatment on pathological changes, the expression level of brain-derived neurotrophic factor (BDNF), and the phosphorylation level of the TrkB receptor (p-TrkB) in the hippocampus of mice at two weeks post-CLP (16d) were evaluated using histological, immunofluorescence, immunohistochemistry, and western blot analyses.
The CLP surgery induced and sustained cognitive impairment in mice with sepsis for a minimum of three weeks following the surgery. Compared to mice subjected to CLP alone, the administration of LGG improved the survival of mice with sepsis and notably enhanced their cognitive functioning. Moreover, LGG supplementation significantly alleviated the decrease in hippocampal BDNF expression and p-TrkB phosphorylation levels caused by sepsis, preserving neuronal survival and mitigating the pathological changes within the hippocampus of mice with sepsis. LGG supplementation mitigates sepsis-related cognitive impairment in mice and preserves BDNF expression and p-TrkB levels in the hippocampus.
Aims To investigate the indicators affecting the early outcome of patients with sepsis and to explore its prognostic efficacy for sepsis. Methods We collected clinical data from 201 patients with ...sepsis admitted to the emergency department of Xijing Hospital between June 2019 and June 2022. The patients were categorized into groups (survival or fatality) based on their 28-day prognosis. The clinical characteristics, biochemical indexes, organ function-related indicators, and disease scores of the patients were analyzed for both groups. Risk factor analysis was conducted for the indicators with significant differences. Results Among the indicators with significant differences between the deceased and survival groups, D-dimer (D-DI), Sequential Organ Failure Assessment (SOFA) score, platelet (PLT), international normalized ratio (INR), and D-DI/PLT were identified as independent risk factors affecting the prognosis of sepsis patients. Receiver operating characteristic (ROC) curves showed that D-DI/PLT (area under the curve (AUC) = 93.9), D-DI (AUC = 89.6), PLT (AUC = 81.3), and SOFA (AUC = 78.4) had good judgment efficacy. Further, Kaplan Meier (K-M) survival analysis indicated that the 28-day survival rates of sepsis patients were significantly decreased when they had high levels of D-DI/PLT, D-DI, and SOFA as well as low PLTs. The hazard ratio (HR) of D-DI/PLT between the two groups was the largest (HR = 16.19). Conclusions D-DI/PLT may be an independent risk factor for poor prognosis in sepsis as well as a clinical predictor of patient prognosis.
Adenocarcinoma in situ and minimally invasive adenocarcinoma are the pre-invasive forms of lung adenocarcinoma. The genomic and immune profiles of these lesions are poorly understood. Here we report ...exome and transcriptome sequencing of 98 lung adenocarcinoma precursor lesions and 99 invasive adenocarcinomas. We have identified EGFR, RBM10, BRAF, ERBB2, TP53, KRAS, MAP2K1 and MET as significantly mutated genes in the pre/minimally invasive group. Classes of genome alterations that increase in frequency during the progression to malignancy are revealed. These include mutations in TP53, arm-level copy number alterations, and HLA loss of heterozygosity. Immune infiltration is correlated with copy number alterations of chromosome arm 6p, suggesting a link between arm-level events and the tumor immune environment.
Isoliquiritigenin (ISL) is a flavonoid with a chalcone structure extracted from the natural herb Glycyrrhiza glabra. Its anti-inflammatory, antibacterial, antioxidant, and anticancer activities have ...been extensively studied. Moreover, ISL also possess hypolipidemic and atherosclerosis-reducing effects. However, its cholesterol-lowering mechanisms have not been reported yet. Niemann Pick C1 Like 1 (NPC1L1) is a specific transporter of cholesterol uptake. In this study, we found for the first time that ISL downregulates NPC1L1 expression and competitively inhibits cellular cholesterol uptake by binding to NPC1L1 in a concentration-dependent manner in vitro. This study provides a theoretical basis for further investigation of the molecular mechanisms of its cholesterol-lowering effect in vivo and inspired emerging drug research for cholesterol-lowering purposes through NPC1L1 inhibition.
Urine-based testing is promising for noninvasive diagnosis of urothelial carcinoma (UC) but has suboptimal sensitivity for early-stage tumors. Herein, we developed a multitarget urine tumor DNA test, ...UI-Seek, for UC detection and evaluated its clinical feasibility. The prediction model was developed in a retrospective cohort (n = 382), integrating assays for FGFR3 and TERT mutations and aberrant ONECUT2 and VIM methylation to generate a UC-score. The test performance was validated in a double-blinded, multicenter, prospective trial (n = 947; ChiCTR2300076543) and demonstrated a sensitivity of 91.37% and a specificity of 95.09%. The sensitivity reached 75.81% for low-grade Ta tumors and exceeded 93% in high-grade Ta and higher stages (T1 to T4). Simultaneous identification of both bladder and upper urinary tract tumors was enabled with sensitivities exceeding 90%. No significant confounding effects were observed regarding benign urological diseases or non-UC malignancies. The test showed improved sensitivities over urine cytology, the NMP22 test, and UroVysion FISH alongside comparable specificities. The single-target accuracy was greater than 98% as confirmed by Sanger sequencing. Post-surgery UC-score decreased in 97.7% of subjects. Overall, UI-Seek demonstrated robust performance and considerable potential for the early detection of UC.
Stroke is an illness with high morbidity, disability and mortality that presents a major clinical challenge. Sanhua decoction (SHD) has been widely used to treat ischaemic stroke in the clinic. ...However, the potential mechanism of SHD remains unknown.
To elucidate the multitarget mechanism of SHD in ischaemic stroke through network pharmacology and bioinformatics analyses.
Network pharmacology and experimental validation approach was used to investigate the bioactive ingredients, critical targets and potential mechanisms of SHD against ischaemic stroke. Four herbal names of SHD, 'ischemic stroke' or 'stroke' was used as a keyword to search the relevant databases. SH-SY5Y cells were treated with various concentrations of SHD (12.5, 25, 50 or 100 μg/mL) for 4 h, exposed to oxygen and glucose deprivation (OGD) for 1 h, then reoxygenation for 24 h. The cell viability was detected by MTT, the lactate dehydrogenase (LDH) was evaluated by ELISA, and protein expression was detected by western blots.
SHD treatment increased the survival rate from 65.9 ± 4.3 to 85.56 ± 5.7%. The median effective dose (ED
50
) was 47.1 μg/mL, the LDH decreased from 288.0 ± 12.0 to 122.8 ± 9.1 U/L and the cell apoptosis rate decreased from 33.6 ± 1.8 to 16.3 ± 1.2%. Western blot analysis revealed that SHD increased the levels of p-PI3k, p-Akt and p-CREB1, and decreased the expression of TNF-α and IL-6.
This study suggests that SHD protects against cerebral ischaemic injury via regulation of the PI3K/Akt/CREB1 and TNF pathways.
Elevated cholesterol significantly increases the risk of developing atherosclerosis and coronary heart disease. The key to treating hypercholesterolemia is lowering plasma cholesterol levels. There ...have been no studies on the cholesterol-lowering potential of parthenolide (PTL), a naturally occurring small molecule from Tanacetum parthenium. Here, we first put forth PTL’s cholesterol-lowering ability to inhibit cellular uptake of cholesterol in a dose-dependent manner. Its performance was on par with the positive control drug, ezetimibe. Niemann–Pick C1 Like-1 (NPC1L1) has been identified as a potential therapeutic target for hypercholesterolemia. The interaction of PTL with NPC1L1 could be explained by the results of molecular docking and filipin staining further reinforces this hypothesis. Furthermore, PTL reduced the expression of NPC1L1 in HepG2 cells in a concentration-dependent manner, which suggests that PTL functions as a potential NPC1L1 inhibitor with therapeutic potential for hypercholesterolemia.
Background
Methotrexate (MTX), utilized as a graft-versus-host disease (GvHD) prophylactic agent in allogeneic hematopoietic stem cell transplantation (allo-HSCT), has been proven to effectively ...decrease the occurrence of the peri-engraftment syndrome (Peri-ES) and acute GvHD (aGvHD). Changes in the pharmacodynamics of MTX are closely associated with gene polymorphisms in genes encoding drug-metabolizing enzymes and transporters. Nevertheless, the current studies mainly concentrate on leukemia or autoimmune diseases, and limited studies on allo-HSCT were reported.
Methods
Here, we retrospectively assessed the relationship between MTX-related transporter and metabolizing enzyme gene polymorphisms, clinical characteristics, and outcomes in 57 pediatric patients who received haploid HSCT (haplo-HSCT) with malignant tumors at a single center.
Results
We discovered all gene polymorphisms were in the Hardy–Weinberg equilibrium in our cohort. We discovered a significant correlation between platelet recovery time and
ABCB1
(1236C>T) (
p
= 0.042). Compared with patients with
SLCO1B1
(1865+4846T>C) TT, patients with
SLCO1B1
(1865+4846T>C) TC/CC had an increased incidence of Peri-ES (
p
= 0.030). Based on the multivariate Cox analysis, we discovered that
SLCO1B1
(1865+4846T>C) TT genotype was an independent protective factor for Peri-ES morbidity (hazard ratio (HR) = 0.464,
p
= 0.031), and the dose of mononuclear cells reinfused was significantly correlated with II–IV aGvHD (HR = 2.604,
p
= 0.039).
Conclusion
In summary, our findings prove that the host’s genotypes might modify the risk of developing Peri-ES, contribute to a better understanding of the inter-individual difference in efficacy, and facilitate the development of individualized approaches to GvHD prophylaxis.
Purpose
Postoperative bleeding is a potentially fatal complication after lung surgery and usually requires re-operation. The aim of this study was to analyze the characteristics of bleeding-related ...re-exploration following pulmonary resection and reduce the incidence of this complication.
Methods
From January 2016 to December 2020, 14,104 patients underwent pulmonary resection for lung cancer or pulmonary nodule at Fudan University Shanghai Cancer Center, China. We evaluated cases with bleeding-related re-exploration, and analyzed the relationship between postoperative bleeding and clinical characteristics. We further developed a protocol to reduce the proportion of bleeding-related re-exploration in our center.
Results
Bleeding-related re-exploration occurred in 85 (0.60%) out of 14,104 patients. The sources of postoperative bleeding included surgical incision (20, 23.53%), parietal pleura (20, 23.53%), bronchial artery (14, 16.47%), lung parenchyma (13, 15.29%), pulmonary vessel (5, 5.88%) and rare source of bleeding. There were various patterns of postoperative bleeding. Open thoracotomy had a significantly higher bleeding rate than video-assisted thoracoscopic surgery (VATS) (1.27% vs 0.34%,
p <
0.0001). The bleeding rate of pneumonectomy, lobectomy, segmentectomy and wedge resection was significantly different (1.78%, 0.88%, 0.46% vs 0.28%,
p <
0.0001). All patients were discharged successfully except for one patient died of respiratory failure. A protocol based on these findings was developed to reduce the proportion of bleeding-related re-exploration in our center.
Conclusion
Our findings revealed that the source of bleeding, surgical approach and procedure affected the pattern of postoperative bleeding. Postoperative bleeding could be managed properly on the timely decision of re-exploration considering its origin, severity, onset and risk factors.
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