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 To describe the significance of the pretreatment inflammatory indicators in predicting the prognosis of patients with esophageal squamous cell carcinoma (ESCC) after undergoing radical radiotherapy. Methods The data of 246 ESCC patients who underwent radical radiotherapy were retrospectively collected. Receiver operating characteristic (ROC) curves were drawn to determine the optimal cutoff values for platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII). The Kaplan-Meier method was used for survival analysis. We conducted univariate and multivariate analyses by using the Cox proportional risk regression model. Software R (version 4.2.0) was used to create the nomogram of prognostic factors. Results The results of the ROC curve analysis showed that the optimal cutoff values of PLR, NLR, and SII were 146.06, 2.67, and 493.97, respectively. The overall response rates were 77.6% and 64.5% in the low and high NLR groups, respectively (P<0.05). The results of the Kaplan-Meier survival analysis revealed that the prognosis of patients in the low PLR, NLR, and SII group was better than that of patients in the high PLR, NLR, and SII group (all P<0.05). The results of the multivariate Cox regression analysis showed that gender, treatment modalities, T stage, and NLR were independent factors affecting the overall survival (OS). In addition, T stage and NLR were independent factors affecting the progression-free survival (PFS) (all P<0.05). The nomogram models of OS and PFS prediction were established based on multivariate analysis. The C-index values were 0.703 and 0.668. The calibration curves showed excellent consistency between the predicted and observed OS and PFS. Conclusion The pretreatment values of PLR, NLR, and SII are correlated with the prognosis of patients with ESCC who underwent radical radiotherapy. Moreover, NLR is an independent factor affecting the OS and PFS of ESCC patients. The NLR-based nomogram model has a good predictive ability.

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.

Ecto-nucleotide pyrophosphatases/phosphodiesterases(ENPPs)are involved in the hydrolysis of different purine nu-cleotides in a range of physiological processes.In recent years,it has also been found to be involved in tumor progression,with ENPP1 often overexpressed in local recurrence and tumor metas-tasis,which is associated with poor prognosis and survival in a range of solid tumors.The role of ENPP1 in tumors is mainly fo-cused on tumor proliferation,metastasis,immunity,recurrence,etc.,and it is speculated that ENPP1 can be used as a prognos-tic indicator for a variety of tumors.ENPP1 promotes the immu-nosuppressive tumor microenvironment by being obliquely in-volved in the regulation of ATP/adenosine homeostasis by com-bining with other components,which crosses with interferon gene stimulators to impair its potent immune response through the hy-drolysis of the effector 2',3'-cyclic GMP-AMP.Therefore,EN-PP1 blockade has become an effective means to induce immune remodeling and inhibit tumorigenesis and development.The ex-isting ENPP1 inhibitors mainly include natural small molecule compounds,nucleotide ENPP1 inhibitors,non-nucleotide EN-PP1 inhibitors,and novel small molecule ENPP1 inhibitors.So far,a small number of ENPP1 inhibitors have been developed and are rarely suitable for in vivo experiments,and they are still in the stage of developing effective compounds or lead com-pounds,and the research on ENPP1 inhibitors needs to be fur-ther studied.This review summarizes and discusses the role of ENPP1 in tumors,and summarizes the current research progress of various ENPP1 agents and their current research progress,in order to provide a reference for further research on the prepara-tion of drug candidates.

Objective To compare the safety and efficacy of endovascular treatment(EVT)transradial approach and transfemoral approach in patients with acute ischemic stroke with large vessel occlusion in the posterior circulation.Methods Patients with acute ischemic stroke with large vessel occlusion in the posterior circulation admitted to the Stroke Center of Linyi People's Hospital,Shandong Second Medical University from February 2022 to April 2024 were retrospectively recruited.The baseline and clinical data were collected,including age,sex,past medical history(hypertension,diabetes mellitus,hyperlipidemia,atrial fibrillation,coronary artery disease,myocardial infarction and stroke),smoking,blood pressure at admission,National Institutes of Health stroke scale(NIHSS)score at admission,modified Rankin scale(mRS)score before the onset of stroke,Alberta stroke program early CT score(ASPECTS),whether intravenous thrombolysis was performed,volume of core infarct zone,volume of hypoperfused zone,occlusion location,etiology of stroke,time indexes(including time from onset to door,time from door to arterial puncture,arterial puncture to recanalization,and time from onset to revascularization),anesthesia modality,EVT first-line strategy,number of passes and whether with vascular access conversion.Clinical data included 90-day postoperative mRS scores,postoperative puncture site complications in 24 hours,symptomatic intracranial hemorrhage at 72 hours postoperatively,modified thrombolysis in cerebral infarction(mTICI)grade at the last angiography introperative and length of stay.The groups were categorized into transradial(TRA)and transfemoral(TFA)groups according to the final access route for EVT.The baseline and clinical data of the two groups were compared.Results A total of 129 patients underwent EVT with acute ischemic stroke with large vessel occlusion in the posterior circulation were finally included,including 47 patients in TRA group and 82 patients in TFA group.The differences about sex,age,past medical history,smoking,blood pressure at admission,NIHSS score at admission,mRS score before the onset of the stroke,ASPECTS,whether intravenous thrombolysis was performed,volume of core infarct zone,volume of hypoperfused zone,occlusion location,etiology of stroke,anesthesia modality,EVT first-line strategy,number of passes,mTICI grade at the last angiography introperative and other aspects were not statistically significant(all P＞0.05).The good prognosis rate at 90 d after surgery(53.2％[25/47]vs.48.8％[40/82],P=0.630),distribution of mRS scores at 90d postoperatively(P=0.991),all-cause mortality at 90 days after surgery(27.7％[13/47]vs.28.0％[23/82],P=1.000),rate of good recanalization(mTICI grade≥2b)on intraoperative last angiogram(97.9％[46/47]vs.95.1％[78/82],P=0.436),rate of complication of puncture site(4.3％[2/47]vs.12.2％[10/82],P=0.209)between the two groups were not statistically significant.The time from door to arterial puncture was significantly longer in the TRA group than in the TFA group,and the difference between the two groups was statistically significant(122.00[95.00,153.00]min vs.105.00[80.25,118.00]min,Z=-2.937,P=0.03);average length of stay in the TFA group was significantly longer than that of the TRA group,and the difference between the two groups was statistically significant(6.00[4.95,7.05]d vs.7.00[6.95,8.88]d,Z=-2.573,P=0.010).Conclusions Patients who underwent EVT via radial or femoral artery approach with acute ischemic stroke with large vessel occlusion in the posterior circulation had similar safety and efficacy,and the number of days of hospitalization was shorter via the TRA.However,more large prospective randomized controlled clinical trials are needed to validate the results of this study.

Objective:Quantitative analysis of policies on equalization of basic public health services was used,to comprehensive understanding of characteristics and the use of combinations of policy tools,and to provide recommendations for promoting equalization of basic public health services in China.Methods:The research object was policies on equalization of basic public health services by the central government from 2009 to 2022,and a three-dimensional policy analysis framework of"Policy tools(dimension X)-Stakeholders(dimension Y)-Policy process(dimension Z)"was constructed to carry out the content analysis of policies.Results:The proportion of supply-oriented policy tools was reasonable,and policy focus on government departments and policy implementation stage;Public health programs have been mainly used,and capacity enhancement of primary health care institutions has been valued and given financial and human resources support.However,there were structural dysfunction,imbalance in policy patterns of interest subjects,and uneven attention at policy stages.Suggestions:Promote the optimization of internal structure of policy tools,diversify policy attention to stakeholders,and rationalize distribute policy phases.

Objective:To evaluate the effect of s-ketamine on perioperative myocardial injury in patients undergoing liver transplantation.Methods:This was a prospective randomized controlled study. Sixty American Society of Anesthesiologists Physical Status classification Ⅲ or Ⅳ patients, aged 18-64 yr, with New York Heart Association classⅠ-Ⅲ, undergoing elective liver transplantation with general anesthesia in our hospital from May to October 2023, were divided into 2 groups ( n=30 each) using a random number table method: s-ketamine group (group S) and control group (group C). In group S, s-ketamine was intravenously injected at a dose of 0.5 mg/kg after induction of anesthesia, followed by an infusion of 0.5 mg·kg -1·h -1 until the end of surgery. The equal volume of normal saline was given instead in group C. Central venous blood samples were collected after induction of anesthesia (T 0), at 30 min of anhepatic phase (T 1), 30 min of neopepatic phase (T 2), abdominal closure (T 3), 24 h after operation (T 4) and 72 h after operation (T 5) for determination of the concentrations of serum high-sensitivity cardiac troponin I, creatine kinase-MB isoenzyme, N-terminal pro-B-type natriuretic peptide, tumor necrosis factor-α, interleukin-6 (IL-6), IL-10 and high-mobility group protein B1 by enzyme-linked immunosorbent assay. The occurrence of adverse cardiac events during surgery and within 24 h after surgery, postoperative mechanical ventilation time, time of intensive care unit stay, and postoperative length of hospital stay were recorded. Results:Compared with group C, the concentrations of serum high-sensitivity cardiac troponin I, creatine kinase-MB isoenzyme, N-terminal pro-B-type natriuretic peptide, tumor necrosis factor-α and IL-6 at T 2-5 and high-mobility group protein B1 at T 2-4 were significantly decreased, the concentrations of serum IL-10 were increased at T 2-5, the incidence of myocardial ischemia was decreased, the mechanical ventilation time was shortened ( P<0.05), and no significant change was found in the time of intensive care unit stay and postoperative length of hospital stay in S group ( P>0.05). Conclusions:Intraoperative usage of s-ketamine can inhibit the inflammatory responses and reduce perioperative myocardial injury in the patients undergoing liver transplantation.