Objective: Whether elevation in plasma levels of amyloid and tau protein biomarkers are better indicators of cognitive decline than higher baseline levels in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) remains understudied. Methods: We included 67 participants with twice testing for AD-related plasma biomarkers via immunomagnetic reduction (IMR) assays (amyloid beta [Aβ]1-40, Aβ1-42, total tau [t-Tau], phosphorylated tau [p-Tau] 181, and alpha-synuclein [α-Syn]) and the Mini-Mental State Examination (MMSE) over a 1-year interval. We examined the correlation between biomarker levels (baseline vs. longitudinal change) and annual changes in the MMSE scores. Receiver operating characteristic curve analysis was conducted to compare the biomarkers. Results: After adjustment, faster cognitive decline was correlated with lower baseline levels of t-Tau (β=0.332, p=0.030) and p-Tau 181 (β=0.369, p=0.015) and rapid elevation of t-Tau (β=-0.330, p=0.030) and p-Tau 181 levels (β=-0.431, p=0.004). However, the levels (baseline and longitudinal changes) of Aβ1-40, Aβ1-42, and α-Syn were not correlated with cognitive decline. aMCI converters had lower baseline levels of p-Tau 181 (p=0.002) but larger annual changes (p=0.001) than aMCI non-converters. The change in p-Tau 181 levels showed better discriminatory capacity than the change in t-Tau levels in terms of identifying AD conversion in patients with aMCI, with an area under curve of 86.7% versus 72.2%. Conclusion We found changes in p-Tau 181 levels may be a suitable biomarker for identifying AD conversion.

Objective: Whether elevation in plasma levels of amyloid and tau protein biomarkers are better indicators of cognitive decline than higher baseline levels in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) remains understudied. Methods: We included 67 participants with twice testing for AD-related plasma biomarkers via immunomagnetic reduction (IMR) assays (amyloid beta [Aβ]1-40, Aβ1-42, total tau [t-Tau], phosphorylated tau [p-Tau] 181, and alpha-synuclein [α-Syn]) and the Mini-Mental State Examination (MMSE) over a 1-year interval. We examined the correlation between biomarker levels (baseline vs. longitudinal change) and annual changes in the MMSE scores. Receiver operating characteristic curve analysis was conducted to compare the biomarkers. Results: After adjustment, faster cognitive decline was correlated with lower baseline levels of t-Tau (β=0.332, p=0.030) and p-Tau 181 (β=0.369, p=0.015) and rapid elevation of t-Tau (β=-0.330, p=0.030) and p-Tau 181 levels (β=-0.431, p=0.004). However, the levels (baseline and longitudinal changes) of Aβ1-40, Aβ1-42, and α-Syn were not correlated with cognitive decline. aMCI converters had lower baseline levels of p-Tau 181 (p=0.002) but larger annual changes (p=0.001) than aMCI non-converters. The change in p-Tau 181 levels showed better discriminatory capacity than the change in t-Tau levels in terms of identifying AD conversion in patients with aMCI, with an area under curve of 86.7% versus 72.2%. Conclusion We found changes in p-Tau 181 levels may be a suitable biomarker for identifying AD conversion.

Objective: Whether elevation in plasma levels of amyloid and tau protein biomarkers are better indicators of cognitive decline than higher baseline levels in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) remains understudied. Methods: We included 67 participants with twice testing for AD-related plasma biomarkers via immunomagnetic reduction (IMR) assays (amyloid beta [Aβ]1-40, Aβ1-42, total tau [t-Tau], phosphorylated tau [p-Tau] 181, and alpha-synuclein [α-Syn]) and the Mini-Mental State Examination (MMSE) over a 1-year interval. We examined the correlation between biomarker levels (baseline vs. longitudinal change) and annual changes in the MMSE scores. Receiver operating characteristic curve analysis was conducted to compare the biomarkers. Results: After adjustment, faster cognitive decline was correlated with lower baseline levels of t-Tau (β=0.332, p=0.030) and p-Tau 181 (β=0.369, p=0.015) and rapid elevation of t-Tau (β=-0.330, p=0.030) and p-Tau 181 levels (β=-0.431, p=0.004). However, the levels (baseline and longitudinal changes) of Aβ1-40, Aβ1-42, and α-Syn were not correlated with cognitive decline. aMCI converters had lower baseline levels of p-Tau 181 (p=0.002) but larger annual changes (p=0.001) than aMCI non-converters. The change in p-Tau 181 levels showed better discriminatory capacity than the change in t-Tau levels in terms of identifying AD conversion in patients with aMCI, with an area under curve of 86.7% versus 72.2%. Conclusion We found changes in p-Tau 181 levels may be a suitable biomarker for identifying AD conversion.

Objective: Whether elevation in plasma levels of amyloid and tau protein biomarkers are better indicators of cognitive decline than higher baseline levels in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) remains understudied. Methods: We included 67 participants with twice testing for AD-related plasma biomarkers via immunomagnetic reduction (IMR) assays (amyloid beta [Aβ]1-40, Aβ1-42, total tau [t-Tau], phosphorylated tau [p-Tau] 181, and alpha-synuclein [α-Syn]) and the Mini-Mental State Examination (MMSE) over a 1-year interval. We examined the correlation between biomarker levels (baseline vs. longitudinal change) and annual changes in the MMSE scores. Receiver operating characteristic curve analysis was conducted to compare the biomarkers. Results: After adjustment, faster cognitive decline was correlated with lower baseline levels of t-Tau (β=0.332, p=0.030) and p-Tau 181 (β=0.369, p=0.015) and rapid elevation of t-Tau (β=-0.330, p=0.030) and p-Tau 181 levels (β=-0.431, p=0.004). However, the levels (baseline and longitudinal changes) of Aβ1-40, Aβ1-42, and α-Syn were not correlated with cognitive decline. aMCI converters had lower baseline levels of p-Tau 181 (p=0.002) but larger annual changes (p=0.001) than aMCI non-converters. The change in p-Tau 181 levels showed better discriminatory capacity than the change in t-Tau levels in terms of identifying AD conversion in patients with aMCI, with an area under curve of 86.7% versus 72.2%. Conclusion We found changes in p-Tau 181 levels may be a suitable biomarker for identifying AD conversion.

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

Objective To investigate the clinical feasibility and safety of endoscopic ultrasonography(EUS)combined with modified endoscopic mucosal resection(EMR)in the treatment of rectal neuroendo-crine tumors(RNETs).Methods A total of 48 patients diagnosed with RNETs by colonoscopy in the depart-ment of gastroenterology in this hospital from December 2021 to June 2023 were selected as the study objects.Patients were randomly divided into the study group(EUS combined with modified EMR,n=16),the control 1 group(traditional EMR,n=16)and the control 2 group[endoscopic submucosal dissection(ESD),n=16].The operation time,R0 resection rate and postoperative complications of each group were observed.Endoscop-ic ultrasonography was followed up 3 and 6 months after surgery to determine whether there was any recur-rence.Results The operative time of the study group[(17.813±0.379)min]was significantly shorter than that of the control 2 group[(36.250±3.296)min],the difference was statistically significant(P＜0.05),but compared with the control 1 group[(16.375±1.996)min],there was no significant difference(P＞0.05).The incidence of complications in the study group(6.2％)was significantly lower than that in the control 2 group(37.5％),the difference was statistically significant(P＜0.05).while the incidence of complications in the study group was not significantly higher than that in the control 1 group(12.5％,P＞0.05).R0 removal rate in the study group(93.8％)was significantly higher than that in the control 1 group(62.5％)and the control 2 group(75.0％),the difference was statistically significant(P＜0.05).Conclusion EUS combined with modified EMR has more advantages than EMR and ESD in the treatment of RNETs,and has certain fea-sibility and safety,which is convenient for clinical application.

Objective: Whether elevation in plasma levels of amyloid and tau protein biomarkers are better indicators of cognitive decline than higher baseline levels in patients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) remains understudied. Methods: We included 67 participants with twice testing for AD-related plasma biomarkers via immunomagnetic reduction (IMR) assays (amyloid beta [Aβ]1-40, Aβ1-42, total tau [t-Tau], phosphorylated tau [p-Tau] 181, and alpha-synuclein [α-Syn]) and the Mini-Mental State Examination (MMSE) over a 1-year interval. We examined the correlation between biomarker levels (baseline vs. longitudinal change) and annual changes in the MMSE scores. Receiver operating characteristic curve analysis was conducted to compare the biomarkers. Results: After adjustment, faster cognitive decline was correlated with lower baseline levels of t-Tau (β=0.332, p=0.030) and p-Tau 181 (β=0.369, p=0.015) and rapid elevation of t-Tau (β=-0.330, p=0.030) and p-Tau 181 levels (β=-0.431, p=0.004). However, the levels (baseline and longitudinal changes) of Aβ1-40, Aβ1-42, and α-Syn were not correlated with cognitive decline. aMCI converters had lower baseline levels of p-Tau 181 (p=0.002) but larger annual changes (p=0.001) than aMCI non-converters. The change in p-Tau 181 levels showed better discriminatory capacity than the change in t-Tau levels in terms of identifying AD conversion in patients with aMCI, with an area under curve of 86.7% versus 72.2%. Conclusion We found changes in p-Tau 181 levels may be a suitable biomarker for identifying AD conversion.

This study explores the effect and mechanism of Banxia Xiexin Decoction(BXD) in inhibiting colon cancer progression by reshaping tryptophan metabolism. Balb/c mice were assigned into control, model, low-dose BXD(BXD-L), and high-dose BXD(BXD-H) groups. Except the control group, the other groups were subcutaneously injected with CT26-Luc cells for the modeling of colon cancer, which was followed by the intervention with BXD. Small animal live imaging was employed to monitor tumor growth, and the tumor volume and weight were measured. Hematoxylin-eosin(HE) staining was used to observe the pathological changes in mouse tumors. Immunohistochemistry was used to detect Ki67 expression in tumors. Immunofluorescence and flow cytometry were used to detect the infiltration and number changes of CD3~+/CD8~+ T cells in the tumor tissue. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of interferon-gamma(IFN-γ) and interleukin-2(IL-2) in tumors. Targeted metabolomics was employed to measure the level of tryptophan(Trp) in the serum, and the Trp content in the tumor tissue was measured. Western blot and RT-qPCR were employed to determine the protein and mRNA levels, respectively, of indoleamine 2,3-dioxygenase 1(IDO1), MYC proto-oncogene, and solute carrier family 7 member 5(SLC7A5) in the tumor tissue. Additionally, a co-culture model with CT26 cells and CD8~+ T cells was established in vitro and treated with the BXD-containing serum. The cell counting kit-8(CCK-8) assay was used to examine the viability of CT26 cells. The content of Trp in CT26 cells and CD8~+ T cells, as well as the secretion of IFN-γ and IL-2 by CD8~+ T cells, was measured. RT-qPCR was used to determine the mRNA levels of MYC and SLC7A5 in CT26 cells. The results showed that BXD significantly inhibited the tumor growth, reduced the tumor weight, and decreased the tumor volume in the model mice. In addition, the model mice showed sparse arrangement of tumor cells, varying degrees of patchy necrosis, and downregulated expression of Ki67 in the tumor tissue. BXD elevated the levels of IFN-γ and IL-2 in the tumor tissue, while upregulating the ratio of CD3~+/CD8~+ T cells and lowering the levels of Trp, IDO1, MYC, and SLC7A5. The co-culture experiment showed that BXD-containing serum reduced Trp uptake by CT26 cells, increased Trp content in CD8~+T cells, enhanced IL-2 and IFN-γ secretion of CD8~+T cells, and down-regulated the mRNA levels of MYC and SLC7A5 in CT26 cells. In summary, BXD can inhibit the MYC/SLC7A5 pathway to reshape Trp metabolism and adjust Trp uptake by CD8~+ T cells to enhance the cytotoxicity, thereby inhibiting the development of colon cancer.
Animals ; Tryptophan/metabolism* ; Colonic Neoplasms/pathology* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Mice, Inbred BALB C ; Humans ; Cell Line, Tumor ; Indoleamine-Pyrrole 2,3,-Dioxygenase/metabolism* ; Female ; Disease Progression ; Cell Proliferation/drug effects* ; Proto-Oncogene Mas ; Male

Objective To explore the clinical value of mini-incision combined with balloon dilatation under the guidance of miniprobe echoendoscope in the treatment of refractory benign esophageal stenosis.Methods From October 2019 to October 2023,30 cases of esophageal early cancer with esophageal scar stenosis after endoscopic submucosal dissection(ESD)were selected and randomly divided into study group(miniprobe echoendoscope guided small incision+balloon dilatation,15 cases)and control group[esophageal radial incision(ERI),15 cases],EUS in the study group judged the hierarchical structure of esophageal wall before operation,and excluded those with esophageal cancer recurrence and submucosal invasive growth.According to miniprobe echoendoscope,the length of scar segment and the scope of scar ring lumen were defined,and the location and length of pre-incision were defined,and then balloon was used to expand step by step.The short-term postoperative complications,Stooler dysphagia scale score and restenosis rate of the two groups were observed,and the feasibility,safety and efficacy were evaluated.Results The incidence of short-term postoperative complications 6.7％in the study group was significantly lower than that 46.7％in the control group,the difference was statistically significant(P＜0.05),and the Stooler dysphagia scale score were(1.133±0.990)and(1.600±0.737)in the study group at 1 and 2 months after operation with significantly lower than those(2.067±1.033)and(2.467±0.915)in the control group,the differences were statistically significant(P＜0.05).Two months after operation,the restenosis rate was 13.3％,which was significantly lower than that 46.7％of the control group,the difference was statistically significant(P＜0.05),and the scar thickness under miniprobe echoendoscope(2.113±0.887)mm was significantly thinner than that(3.353±1.468)mm of the control group,the difference was statistically significant(P＜0.05).Conclusion Preoperative miniprobe echoendoscope evaluation,can accurately locate lesions,endoscopic mini-incision combined with balloon mechanical expansion are safe and effective,with less pain and fewer postoperative complication.

Objective To investigate the effects and mechanism of Xuefu Zhuyu Decoction in oxidative stress in coronary heart disease model rats with heart blood stasis syndrome based on Keap1/Nrf2 signaling pathway.Methods The rats were divided into normal group,sham-operation group,model group,Xuefu Zhuyu Decoction group and trimetazidine group.The rat model of coronary heart disease with heart blood stasis syndrome was established by ligation of the left anterior descending branch of the coronary artery.Xuefu Zhuyu Decoction group and trimetazidine group were administrated with the corresponding drugs at the dosages of 14.04 g/kg and 5.4 mg/kg,respectively,and normal group,sham-operation group and model group were administrated with the same volume of normal saline for 14 days.The general state of rats was observed,body mass was recorded and electrocardiogram was collected.Echocardiography was used to examine cardiac functions(LVEF,LVFS,LVIDd,LVIDs);the morphology of myocardial tissue was observed by HE staining,serum malondialdehyde(MDA),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and total antioxidant capacity(T-AOC)were detected by ELISA,the positive expressions of Keap1,Nrf2,HO-1 and NQO1 in myocardial tissue were detected by immunohistochemistry.Results Compared with the normal group and sham-operation group,the rats in the model group showed signs of mental fatigue,reduced activity,dull fur,purple claws,and a significant decrease in body mass(P<0.01);the ST segment in lead Ⅱ of the electrocardiogram was significantly elevated,LVEF and LVFS were significantly reduced,and LVIDd and LVIDs significantly increased(P<0.01),with severe degeneration and necrosis of myocardial cells,disappearance of striated structures,disordered arrangement of myocardial fibers,infiltration of inflammatory cells;the serum MDA content significantly increased,while the activities of SOD,GSH-Px and T-AOC significantly decreased(P<0.01);the positive expressions of Keap1 and Nrf2 in myocardial tissue significantly increased,while the positive expression of HO-1 and NQO1 significantly decreased(P<0.01).Compared with the model group,the rats in Xuefu Zhuyu Decoction group and trimetazidine group showed improvement in their mental state,increased activity,shiny fur,rosy nails,and significantly increased body mass(P<0.01);the ST segment of the electrocardiogram decreased to varying degrees,with significant increases in LVEF and LVFS,and significant decreases in LVIDd and LVIDs(P<0.01);a large number of myocardial cells survived,the arrangement of myocardial fibers was relatively regular,and the infiltration of inflammatory cells was significantly reduced;the serum MDA content was significantly reduced,while the activities of SOD,GSH-Px and T-AOC significantly increased(P<0.01);the positive expression of Keap1 in myocardial tissue significantly decreased,while the positive expressions of Nrf2,HO-1 and NQO1 significantly increased(P<0.01).Conclusion Xuefu Zhuyu Decoction may inhibit oxidative stress by activating Keap1/Nrf2 signaling pathway to improve the pathological morphology and structural damage of myocardial tissue and promote the recovery of cardiac functions in rats with heart blood stasis syndrome of coronary heart disease.