Purpose: To evaluate the clinical outcomes of endovascular treatment for ruptured vertebral artery dissecting aneurysms (VADAs), with a focus on endovascular protocols tailored to different anatomical subtypes. Materials and Methods: We retrospectively analyzed 44 consecutive patients with ruptured VADAs treated from December 2014 to October 2024. Treatment strategies were guided by aneurysm location: parent artery occlusion (PAO) was used for lesions in non-dominant VAs, while stent-assisted coiling (SAC) reconstruction was used for aneurysms in dominant VAs. Patients were stratified by modified Rankin Scale (mRS) scores at 3-month follow-up (favorable: mRS 0–2; unfavorable: mRS 3–6). Results: All procedures were technically successful, including 12 single SAC, 13 overlapping SAC, and 19 with PAO (2 involving posterior inferior cerebellar artery preservation). Immediate complete occlusion was achieved in 50.0% of single SAC cases, 76.9% overlapping SAC, and 100% in the PAO group. Six (13.6%) procedure-related complications occurred, including 2 hemorrhagic and 4 ischemic events. Thirty patients (68.2%) had favorable outcomes, and the unfavorable outcomes group showed a higher incidence of ischemic events (P=0.012). An initial poor Hunt–Hess grade (≥IV) was an independent risk factor for unfavorable outcomes (odds ratio 6.35, 95% confidence interval 1.24–32.59; P=0.027). Angiographic follow-up was performed for 34 aneurysms, with complete occlusion achieved in 32 (94.1%); the remaining 2 patients were retreated. Conclusion Endovascular management is safe and effective for ruptured VADAs. Anatomical stratification—PAO for non-dominant VA lesions and SAC for dominant VA aneurysms—may help achieve favorable outcomes.

Objective:To investigate the relationship between thoracic aortic calcification (TAC) and autonomic nervous system (ANS) function in patients receiving continuous ambulatory peritoneal dialysis (CAPD).Methods:It was a cross-sectional study. The CAPD patients with dialysis duration >6 months between January and December 2022 were retrospectively enrolled. The baseline clinical data, heart rate variability (HRV) data such as standard deviation of all normal to normal intervals (SDNN), root mean square of successive differences between adjacent normal-to-normal intervals (RMSSD), high frequency (HF), very low frequency (VLF), low frequency (LF), LF/HF, acceleration capacity (AC) and deceleration capacity (DC), and skin sympathetic nerve activity (SKNA) were collected. TAC was defined as TAC score (TACS) >100 AU. The patients were divided into TACS >100 AU group and TACS≤100 AU group based on whether the thoracic aorta was calcified. The differences of those data between the two groups were compared. Logistic regression model was used to analyze the related factors of TAC. Spearman correlation analysis method was used to analyze the correlation between peripheral blood neuropeptide Y, ANS parameters, average amplitude SKNA (aSKNA) and TACS.　Cox regression model was used to analyze the risk factors of all-cause mortality in patients with CAPD.Results:The study included 106 CAPD patients with 50 males (47.2%), age of (46.04±11.10) years and dialysis duration of (41.55±30.52) months. TACS>100 AU group exhibited significantly lower heart rate ( t=2.015, P=0.046), DC ( t=2.131, P=0.035), LF/HF ( Z=3.332, P<0.001) and ln(LF/HF) ( t=3.326, P=0.001), and higher AC ( t=-2.392, P=0.019) than TACS≤100 AU group. Multivariate logistic regression analysis results showed that after adjusting for age and eosinophil count, lnVLF ( OR=0.66, 95% CI 0.45-0.98, P=0.038), lnLF ( OR=0.69, 95% CI 0.49-0.97, P=0.032), DC ( OR=0.79, 95% CI 0.64-0.99, P=0.039) and AC ( OR=1.32, 95% CI 1.04-1.68, P=0.021) were independently correlated with the risk of TAC. Spearman correlation analysis showed that neuropeptide Y level in peripheral blood was correlated with aSKNA ( r=0.23, P=0.017), lnSDNN ( r=-0.20, P=0.036) and TACS ( r=0.19, P=0.048). During the follow-up period of (25.8±4.2) months, 5 patients (4.72%) died, including 1 patient in the TACS≤100 AU group and 4 patients in the TACS>100 AU group. Compared with the survival group, the death group had higher TACS ( Z=-2.262, P=0.024) and lower LF/HF ( Z=-2.750, P=0.006). Cox regression analysis results showed that increased ln(LF/HF) was an independent influencing factor for all-cause mortality in CAPD patients ( HR=0.22, 95% CI 0.05-0.83, P=0.026). Conclusions:HRV parameters (lnVLF, lnLF, AC and DC) of CAPD patients are independently associated with TAC. The dysfunction of ANS in CAPD patients (especially the decreased vagus nerve activity) may promote TAC.

Objective To evaluate the association between self-reported neighborhood walkability environments and mortality in China.Methods The Prospective Urban Rural Epidemiology study in China(PURE-China)recruited 47 931 participants aged 35-70 from 12 provinces in China between 2005 and 2009.Neighborhood environmental indicators were collected using the Neighborhood Environment Walkability Scale(NEWS)questionnaire,with higher scores indicating better walkable environments.The primary outcomes were all-cause mortality and cardiovascular mortality,using Cox fragile model to evaluate the association between community walkability and outcomes,as well as exploring mediating pathways.Results Of 35 490 participants included in this study,60%were female,with a mean(SD)age of 51.5(9.6)years.The median follow-up was 11.7 years.This study found an association between higher community walkability score and reduced risk of all-cause mortality,with the total score(HR=0.85;95%CI,0.80-0.89),land-use mix(HR=0.84;95%CI,0.79-0.88),and crime safety(HR=0.84;95%CI,0.80-0.89)showing the most significant associations.NEWS can affect long-term adverse outcomes through lifestyle.Conclusions In the Chinese population,favorable community walkability is associated with lower all-cause mortality risk,which may support policymakers to take actions to mitigate the adverse effects of poor community en-vironments on health.

OBJECTIVE To investigate of the regulatory effects of Budi Shenlian Recipe on gut microbiota and the phenotypic transition of tumor-associated macrophages(TAMs)in colorectal cancer(CRC)mice.METHODS Forty male BALB/c mice were divided into blank control group,model group,positive control group,high-dose Budi Shenlian Recipe group,and low-dose Budi Shenlian Recipe group(n=8).CRC-bearing models were established by subcutaneous injection of CT26 cells.Additionally,10 male BALB/c mice were divided into the Budi Shenlian Recipe fecal microbiota transplantation(BFMT)group and model fecal microbiota transplantation(MFMT)group(n=5).The gut microbiota of these mice was cleared using a mixed solution of quadruple antibiotics,followed by subcutaneous injection of CT26 cells to construct pseudo-germ-free CRC-bearing mice.Fecal samples from the model group and high-dose Budi Shenlian Recipe group were collected to prepare fecal microbiota solutions.The BFMT group received gavage with fecal microbiota solution from the high-dose Budi Shenlian Recipe group,while the MFMT group received gavage with fecal micro-biota solution from the model group.Tumor volume changes were observed and recorded.HE staining was used to assess pathological changes in tumor tissues.16S sequencing was performed to analyze changes in gut microbiota.Flow cytometry and immunofluorescence staining were used to evaluate the proportion of M1/M2 type TAMs in tumor tissues.ELISA was used to detect differences in TNF-α and IL-10 levels in tumor tissues.RESULTS Compared to the model group,the tumor volume of mice in the positive control group,high-dose Budi Shenlian Recipe group,and low-dose Budi Shenlian Recipe group grew more slowly(P<0.01).HE staining showed necrotic areas in tumor tissues and reduced mitotic figures in the positive control and Budi Shenlian Recipe groups compared to the model group.16S rRNA sequencing showed no significant differences in Chao1 and ACE indices between the high-dose Budi Shenlian Recipe group and the model group.PCoA analysis indicated a distinct microbial community structure between the blank group and mod-el group,with the microbial structure of CRC mice in the Budi Shenlian Recipe group closer to that of the blank group.Compared to the blank group,the model group showed a significant decrease in the proportion of Muribaculaceae,Muribaculum,Alloprevotella,and Prevotellaceae_UCG-001,and a significant increase in Lachnospiraceae_NK4A136_group,Bacteroides,and Helicobacter.After admin-istering Budi Shenlian Recipe to CRC mice,the community structure of some mice partially reverted to the level of the blank group.Transcriptome sequencing revealed that the most significant biological process(BP)among upregulated genes was the negative regulation of macrophage migration,suggesting that Budi Shenlian Recipe can reduce macrophage migration.Moreover,compared to the model group,the proportion of TAMs cells in the tumor tissues of the Budi Shenlian Recipe group significantly decreased(P<0.001).Simultaneously,compared to the model group,the proportion of M1 type TAMs in the Budi Shenlian Recipe group significant-ly increased(P<0.000 1),while the proportion of M2 type TAMs significantly decreased(P<0.05).Immunofluorescence analysis showed the same trend as flow cytometry.The content of TNF-α in tumor tissues of the Budi Shenlian Recipe group significantly in-creased(P<0.001),and IL-10 content significantly decreased(P<0.001).Additionally,compared to the MFMT group,the tumor volume in the BFMT group grew more slowly(P<0.0001).HE staining showed increased necrotic areas,sparser cell arrangement,and reduced pathological mitosis in the BFMT group.Furthermore,compared to the MFMT group,the proportion of TAMs cells in the tumor tissues of the BFMT group significantly decreased(P<0.01).Compared to the MFMT group,the proportion of M1 type TAMs cells in the BFMT group increased(P<0.000 1),while the proportion of M2 type TAMs cells decreased(P<0.01).Immunofluores-cence analysis further confirmed that Budi Shenlian Recipe fecal microbiota transplantation can reduce the proportion of TAMs in the tumor tissues of CRC mice and promote the conversion from M2 to M1 type,thereby reducing immune suppression in the tumor micro-environment.CONCLUSION Budi Shenlian Recipe can improve gut microbiota dysbiosis in CRC mice and exert anti-CRC effects by reducing tumor infiltration of TAMs and modulating the phenotypic transition of TAMs.There may be a certain correlation between these two effects.

Objective To investigate the influencing factors for the short-term prognosis of patients with alcohol-related liver diseases-acute-on-chronic liver failure(ALD-ACLF)comorbid with infection.Methods A total of 89 ALD-ACLF patients with infection who were admitted to the Fifth Medical Center of PLA General Hospital from January 2019 to December 2021 were enrolled as subjects,and related clinical data were collected at baseline(time of patient enrollment).According to the 28-day survival status of patients,they were divided into survival group with 53 patients and death group with 36 patients,and baseline clinical data were compared between the two groups.The t-test was used for comparison of normally distributed continuous data between groups,and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between groups;the chi-square test was used for comparison of categorical data between groups.A non-conditional Logistic regression analysis was used to perform the multivariate analysis.The Z-test was used for comparison of the area under the ROC curve(AUC),and the diagnostic value of the model was assessed.Results Compared with the survival group,the death group had significantly higher hemoglobin(t=-2.397,P=0.019),alanine aminotransferase(Z=-3.437,P=0.001),gamma-glutamyl transpeptidase(Z=-2.617,P=0.009),creatinine(Z=-3.938,P<0.001),blood urea nitrogen(Z=-3.423,P=0.001),NH3(Z=-4.406,P<0.001),international normalized ratio(Z=-3.428,P=0.001),C-reactive protein(Z=-2.128,P=0.033),procalcitonin(Z=-2.441,P=0.015),Model for End-Stage Liver Disease(MELD)score(t=-4.817,P<0.001),incidence rate of acute kidney injury(χ2=21.602,P<0.001),incidence rate of pulmonary infection(χ2=4.866,P=0.027),and incidence rate of shock(χ2=16.285,P<0.001),as well as significantly lower albumin(Z=-2.473,P=0.013)and incidence rate of abdominal infection(χ2=5.897,P=0.015).The multivariate analysis showed that NH3(odds ratio[OR]=1.027,95%confidence interval[CI]:1.006-1.049,P=0.012),MELD score(OR=1.103,95%CI:1.011-1.203,P=0.027],and the incidence rate of shock(OR=6.326,95%CI:1.533-26.101,P=0.011)were independent risk factors for 28-day mortality in ALD-ACLF patients comorbid with infection.Based on these factors,a predictive model was established as Y=0.027×NH3+0.098×MELD score+1.845×shock-4.111.The ROC curve analysis showed that the new model had an AUC of 0.861,a sensitivity of 77.78%,and a specificity of 88.68%,while MELD score had an AUC of 0.776,a sensitivity of 77.78%,and a specificity of 67.92%,suggesting that the new model had a significantly higher diagnostic value than MELD score(Z=2.136,P=0.032 6).Conclusion ALD-ACLF patients with infection tend to have a poor short-term prognosis,and MELD score,NH3,and shock are influencing factors for the short-term prognosis of such patients.The combination of these three factors has a high value in predicting short-term prognosis.

The complement component 4 binding protein alpha(C4BPA)gene is the alpha chain of complement binding protein 4.As a plasma protein involved in the complement and coagulation systems,it can influence immune responses and lipid metabolism.In order to study the polymor-phism of C4BPA gene and its correlation with milk quality traits in Chinese Holstein cows,genom-ic DNA was extracted from blood samples of 92 Chinese Holstein cows,and the target fragment of C4BPA gene was amplified by PCR,and the association analysis was performed by using direct se-quencing to obtain the SNP loci and milk quality traits.The results showed that among the four SNPs found at the third intron of the C4BPA gene,I3-11 G＞A was highly significantly correlated with milk protein and urea nitrogen(P＜0.05),I3-291 T＞G was significantly correlated with lac-tose(P＜0.05),I3-374 C＞T was highly significantly correlated with lactose and urea nitrogen(P＜0.05),and I3-375 T＞G was highly significantly correlated with lactose(P＜0.05),milk pro-tein and urea nitrogen.The chi-square test values for each point indicated that the population was in genetic equilibrium.Individuals of haplotype combination H1 H1 had the highest lactose content,and haplotype combination H1H2 can be used as the best haplotype combination in the molecular selection work of dairy cows.

Advancements in artificial intelligence(AI)and emerging technologies are rapidly expanding the exploration of chemical space,facilitating innovative drug discovery.However,the transformation of novel compounds into safe and effective drugs remains a lengthy,high-risk,and costly process.Comprehensive early-stage evaluation is essential for reducing costs and improving the success rate of drug development.Despite this need,no comprehensive tool currently supports systematic evaluation and efficient screening.Here,we present druglikeFilter,a deep learning-based framework designed to assess drug-likeness across four critical dimensions:1)physicochemical rule evaluated by systematic determination,2)toxicity alert investigated from multiple perspectives,3)binding affinity measured by dual-path analysis,and 4)compound synthesizability assessed by retro-route prediction.By enabling automated,multidimensional filtering of compound libraries,druglikeFilter not only streamlines the drug development process but also plays a crucial role in advancing research efforts towards viable drug candidates,which can be freely accessed at https://idrblab.org/drugfilter/.

Alzheimer's disease (AD) is a common neurodegenerative disorder among the elderly, and BuChE has emerged as a potential therapeutic target. In this study, we reported the development of compound 8e, a selective reversible BuChE inhibitor (eqBuChE IC₅₀ = 0.049 μmol/L, huBuChE IC₅₀ = 0.066 μmol/L), identified through extensive virtual screening and lead optimization. Compound 8e demonstrated favorable blood-brain barrier permeability, good drug-likeness property and pronounced neuroprotective efficacy. Additionally, 8e exhibited significant therapeutic effects in zebrafish AD models and scopolamine-induced cognitive impairments in mice. Further, 8e significantly improved cognitive function in APP/PS1 transgenic mice. Proteomics analysis demonstrated that 8e markedly elevated the expression levels of very low-density lipoprotein receptor (VLDLR), offering valuable insights into its potential modulation of the Reelin-mediated signaling pathway. Thus, compound 8e emerges as a novel and potent BuChE inhibitor for the treatment of AD, with significant implications for further exploration into its mechanisms of action and therapeutic applications.

Advancements in artificial intelligence (AI) and emerging technologies are rapidly expanding the exploration of chemical space, facilitating innovative drug discovery. However, the transformation of novel compounds into safe and effective drugs remains a lengthy, high-risk, and costly process. Comprehensive early-stage evaluation is essential for reducing costs and improving the success rate of drug development. Despite this need, no comprehensive tool currently supports systematic evaluation and efficient screening. Here, we present druglikeFilter, a deep learning-based framework designed to assess drug-likeness across four critical dimensions: 1) physicochemical rule evaluated by systematic determination, 2) toxicity alert investigated from multiple perspectives, 3) binding affinity measured by dual-path analysis, and 4) compound synthesizability assessed by retro-route prediction. By enabling automated, multidimensional filtering of compound libraries, druglikeFilter not only streamlines the drug development process but also plays a crucial role in advancing research efforts towards viable drug candidates, which can be freely accessed at https://idrblab.org/drugfilter/.

Objective To investigate the influencing factors for the short-term prognosis of patients with alcohol-related liver diseases-acute-on-chronic liver failure(ALD-ACLF)comorbid with infection.Methods A total of 89 ALD-ACLF patients with infection who were admitted to the Fifth Medical Center of PLA General Hospital from January 2019 to December 2021 were enrolled as subjects,and related clinical data were collected at baseline(time of patient enrollment).According to the 28-day survival status of patients,they were divided into survival group with 53 patients and death group with 36 patients,and baseline clinical data were compared between the two groups.The t-test was used for comparison of normally distributed continuous data between groups,and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between groups;the chi-square test was used for comparison of categorical data between groups.A non-conditional Logistic regression analysis was used to perform the multivariate analysis.The Z-test was used for comparison of the area under the ROC curve(AUC),and the diagnostic value of the model was assessed.Results Compared with the survival group,the death group had significantly higher hemoglobin(t=-2.397,P=0.019),alanine aminotransferase(Z=-3.437,P=0.001),gamma-glutamyl transpeptidase(Z=-2.617,P=0.009),creatinine(Z=-3.938,P<0.001),blood urea nitrogen(Z=-3.423,P=0.001),NH3(Z=-4.406,P<0.001),international normalized ratio(Z=-3.428,P=0.001),C-reactive protein(Z=-2.128,P=0.033),procalcitonin(Z=-2.441,P=0.015),Model for End-Stage Liver Disease(MELD)score(t=-4.817,P<0.001),incidence rate of acute kidney injury(χ2=21.602,P<0.001),incidence rate of pulmonary infection(χ2=4.866,P=0.027),and incidence rate of shock(χ2=16.285,P<0.001),as well as significantly lower albumin(Z=-2.473,P=0.013)and incidence rate of abdominal infection(χ2=5.897,P=0.015).The multivariate analysis showed that NH3(odds ratio[OR]=1.027,95%confidence interval[CI]:1.006-1.049,P=0.012),MELD score(OR=1.103,95%CI:1.011-1.203,P=0.027],and the incidence rate of shock(OR=6.326,95%CI:1.533-26.101,P=0.011)were independent risk factors for 28-day mortality in ALD-ACLF patients comorbid with infection.Based on these factors,a predictive model was established as Y=0.027×NH3+0.098×MELD score+1.845×shock-4.111.The ROC curve analysis showed that the new model had an AUC of 0.861,a sensitivity of 77.78%,and a specificity of 88.68%,while MELD score had an AUC of 0.776,a sensitivity of 77.78%,and a specificity of 67.92%,suggesting that the new model had a significantly higher diagnostic value than MELD score(Z=2.136,P=0.032 6).Conclusion ALD-ACLF patients with infection tend to have a poor short-term prognosis,and MELD score,NH3,and shock are influencing factors for the short-term prognosis of such patients.The combination of these three factors has a high value in predicting short-term prognosis.