Objective To investigate the influencing factors for stroke-associated pneumonia(SAP)in acute ischemic stroke(AIS)patients after endovascular treatment(EVT).Methods A retrospective case-control trial was conducted on 426 AIS patients with large vessel occlusion(LVO)in anterior circulation admitted in the neurological departments from First Affiliated Hospital of Army Medical University and Zigong Third People's Hospital during January 2017 and April 2021.Based on SAP occurrence or not,they were divided into an SAP group and a non-SAP group.Demographic information(gender and age),TOAST stroke subtypes(large artery atherosclerosis type,cardiac embolism type,others),vascular risk factors(hypertension,hyperlipidemia,diabetes,atrial fibrillation,smoking,prior stroke history,smoking),and post-onset clinical data[dysphagia,LDL cholesterol,white blood cells,neutrophils,baseline and postoperative NIHSS scores,endovascular outcomes(mTICI grade 2b or 3),90-day good prognosis(mRS 0-1)]were collected and compared between the 2 groups.Multivariate logistic regression analysis was performed using the parameters with P<0.1 in univariate analysis as independent variables to investigate factors influencing SAP occurrence after EVT in AIS patients.Results Among the 426 participants,SAP occurred in 194 cases(45.5%).Multivariate logistic regression analysis revealed that admission white blood cell count(OR=1.125,95%CI:1.043～1.213,P=0.000 2),postoperative NIHSS score(OR=1.019,95%CI:1.001～1.037,P=0.041),and male(OR=1.687,95%CI:1.078～2.638,P=0.022)were associated with SAP occurrence after EVT in AIS patients.Conclusion Higher admission white blood cell count,elevated postoperative NIHSS score,and male gender are risk factors for SAP in AIS patients after EVT.These risk factors should be focused on clinical practice to control SAP incidence.

ObjectiveTo explore the mechanism of Hei Xiaoyaosan in improving the cognitive function in Alzheimer's disease （AD） from cell apoptosis mediated by the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/nuclear factor kappa B （NF-κB） signaling pathway. MethodsFour-month-old SD male rats were randomly assigned into a blank group， a sham group， a model group， a donepezil hydrochloride （0.45 mg·kg^-1） group， and high-， medium-， and low-dose （15.30， 7.65， and 3.82 g·kg^-1， respectively） Hei Xiaoyaosan groups， with 10 rats in each group. The sham group received bilateral hippocampal injection of 1 μL normal saline， while the other groups received bilateral hippocampal injection of 1 μL beta-amyloid 1-42 （Aβ_1-42） solution for the modeling of AD. Rats were administrated with corresponding agents once a day for 42 consecutive days. The Morris water maze test was carried out to assess the learning and memory abilities of rats. Hematoxylin-eosin staining was employed to observe pathological changes in the hippocampus of rats. Enzyme-linked immunosorbent assay was employed to measure the levels of cysteinyl aspartate-specific proteinase-3 （Caspase-3）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax）. Western blot was employed to determine the protein levels of PI3K， Akt， and NF-κB. A cell model of AD was established by co-culturing Aβ_1-42 and PC12 cells in vitro. Cell viability and apoptosis were detected by the cell-counting kit 8 （CCK-8） assay and flow cytometry （FC）， respectively. ResultsAnimal experiments showed that compared with the blank group， the model group had a prolonged escape latency （P<0.01）， a reduced number of crossing platforms （P<0.01）， disarrangement and a reduced number of hippocampal neurons， up-regulated expression of Bax and Caspase-3， down-regulated expression of Bcl-2 （P<0.01）， decreased p-PI3K/PI3K and p-Akt/Akt levels， and an increased p-NF-κB/NF-κB level （P<0.01）. Compared with the model group， donepezil hydrochloride and high- and medium-dose Hei Xiaoyaosan shortened the escape latency and increased the number of crossing platforms （P<0.05， P<0.01）， improved the arrangement and increased the number of hippocampal neurons， down-regulated the expression levels of Bax and Caspase-3， up-reguated the expression level of Bcl-2 （P<0.05， P<0.01）， increased the p-PI3K/PI3K and p-Akt/Akt levels （P<0.05， P<0.01）， and reduced the p-NF-κB/NF-κB level （P<0.05， P<0.01）. Cell experiments showed that compared with the blank group， the model group exhibited an increased apoptosis rate （P<0.01）. Compared with the model group， the serum containing Hei Xiaoyaosan at various doses improved the cell viability （P<0.01）， and the serum containing Hei Xiaoyaosan at the high dose decreased the cell apoptosis （P<0.01）. ConclusionHei Xiaoyaosan may improve the learning and memory abilities of AD model rats by regulating cell apoptosis， while increasing the vitality and reducing the apoptosis rate of AD model cells via the PI3K/Akt/NF-κB signaling pathway.

ObjectiveTo observe the effects of Hei Xiaoyaosan on the learning and memory abilities of Alzheimer's disease model mice （APP/PS1 mice）， and to explore its mechanism through the inflammatory cascade mediated by nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 （NLRP3）/cysteine aspartate-specific protease （Caspase-1）/gasdermin D （GSDMD） signaling pathway. MethodsSPF-grade 4-month-old APP/PS1 mice were randomly divided into the model group， MCC950 group， and Hei Xiaoyaosan high-， medium-， and low-dose groups. C57BL/6J mice were used as the blank group. After 7 days of adaptive feeding， mice in each group were intervened. The Hei Xiaoyaosan high-， medium-， and low-dose groups were given corresponding doses by gavage （25.79， 12.90， 6.45 g·kg^-1·d^-1）， the MCC950 group was intraperitoneally injected with 10 mg·kg^-1·2 d^-1， and the blank group received the same volume of physiological saline by gavage. After 90 days of intervention， the learning and memory abilities were assessed using the Y maze and Morris water maze tests. The structural changes of hippocampal neurons were observed by hematoxylin-eosin （HE） staining. The expression of amyloid precursor protein （APP） in the hippocampal CA3 region was detected by immunohistochemistry. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interleukin （IL）-10， IL-18， and IL-1β in the hippocampus. Western blot was applied to detect the protein expression of NLRP3， Caspase-1， GSDMD， and GSDMD-N in the hippocampus. Immunofluorescence was used to detect the co-localization of GSDMD-N and ionized calcium-binding adapter molecule-1 （Iba-1） in the hippocampus. Results① In the Y maze test， compared with the blank group， the spontaneous alternation rate of the model group was significantly reduced （P<0.01）. Compared with the model group， the spontaneous alternation rate in the Hei Xiaoyaosan high- and low-dose groups was significantly increased （P<0.01）. ② In the Morris water maze test， during the 1-4 days of the location navigation test， the escape latency time of mice decreased with the extension of training time. On day 4， compared with the blank group， the model group showed a significantly increased escape latency （P<0.05）. Compared with the model group， the MCC950 group and the Hei Xiaoyaosan low-dose group showed significantly reduced escape latency （P<0.05）. In the spatial exploration experiment， compared with the blank group， the number of platform crossings in the model group was significantly reduced （P<0.01）. Compared with the model group， the Hei Xiaoyaosan low-dose group showed significantly increased platform crossings （P<0.05）. ③ HE staining showed that， compared with the blank group， the hippocampal CA3 cells of the model group were damaged， arranged loosely and irregularly， swollen， with unclear boundaries， and the nuclei were pyknotic and deeply stained. MCC950 and all doses of Hei Xiaoyaosan improved the hippocampal CA3 cell damage in APP/PS1 mice to varying degrees. ④ Immunohistochemical results indicated that， compared with the blank group， the expression of APP in the hippocampal CA3 region was significantly increased in the model group （P<0.01）. MCC950 and all doses of Hei Xiaoyaosan could reduce the expression of APP in the hippocampal CA3 region of APP/PS1 mice （P<0.01）. ⑤ ELISA results showed that the levels of IL-18 and IL-1β in the hippocampus of mice in the model group were significantly increased， and IL-10 levels were significantly reduced （P<0.01）. Compared with the model group， the IL-18 levels in the MCC950 group and the Hei Xiaoyaosan medium- and low-dose groups were significantly reduced （P<0.01）. IL-1β levels in the hippocampus of the MCC950 group and Hei Xiaoyaosan high-， medium-， and low-dose groups were significantly decreased （P<0.01）. The IL-10 levels in the hippocampus of the MCC950 group and the Hei Xiaoyaosan medium- and low-dose groups were increased （P<0.05， P<0.01）. ⑥ Western blot results showed that compared with the blank group， the protein levels of NLRP3， Caspase-1， GSDMD， and GSDMD-N in the hippocampus of the model group were significantly elevated （P<0.01）. Compared with the model group， the content of NLRP3 and Caspase-1 in the hippocampus of the treated groups was decreased （P<0.05， P<0.01）. The content of GSDMD in the hippocampus of the Hei Xiaoyaosan high-， medium-， and low-dose groups was reduced （P<0.05， P<0.01）， and the content of GSDMD-N in the hippocampus of the Hei Xiaoyaosan medium- and low-dose groups was decreased （P<0.05， P<0.01）. ⑦ Immunofluorescence results showed that， compared with the blank group， the co-expression of GSDMD-N and Iba-1 in the hippocampus of the model group was significantly increased （P<0.01）. Compared with the model group， the co-expression of GSDMD-N and Iba-1 in the treated groups was significantly reduced （P<0.01）. ConclusionHei Xiaoyaosan may regulate the NLRP3/Caspase-1/GSDMD signaling pathway to affect the release of inflammatory factors， alleviate neuroinflammation，improve hippocampal histopathological changes，and improve learning and memory deficits，thus providing potential therapeutic benefits for Alzheimer's disease.

Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

Background::Hepatitis B poses a heavy burden for children in China, however, the national studies on the distributional characteristics and health care costs of children with severe hepatitis B is still lacking. This study aimed to analyze the disease characteristics, health economic effects, and medical cost for children with severe hepatitis B in China.Methods::Based on patient information in the Hospital Quality Monitoring System, cases with severe hepatitis B were divided into four groups according to age, and the etiology and symptoms of each group were quantified. The cost of hospitalization was calculated for cases with different disease processes, and severity of disease. The spatial aggregation of cases and the relationship with health economic factors were analyzed by Moran’s I analysis. Results::The total number of children discharged with hepatitis B from January 2016 to April 2022 was 1603, with an average age of 10.5 years. Liver failure cases accounted for 43.48% (697/1603) of total cases and cirrhosis cases accounted for 11.23% (180/1603). According to the grouping of disease progression, there were 1292 cases without associated complications, and the median hospitalization cost was $818.12. According to the spatial analysis, the aggregation of cases was statistically significant at the prefectural and provincial levels in 2019, 2020, and 2021 (all P <0.05). The number of severe cases was negatively correlated with gross domestic product (Moran’s I <0) and percentage of urban population (Moran’s I <0), and positively correlated with the number of pediatric beds per million population (Moran’s I >0). Conclusion::The number of severe hepatitis B cases is low in areas with high gross domestic product levels and high urban population ratios, and health care costs have been declining over the years.

Objective:To analyze the association between inflammation-related dietary patterns and the risk for cognitive impairment in older adults aged ≥65 years in longevity areas in China by using reduced rank regression (RRR) analysis.Methods:This study used cross-sectional data from the 2021 Healthy Aging and Biomarkers Cohort Study, including the information about study participants' demographic characteristics, lifestyles, daily life activities, and disease histories. Dietary intake was obtained by using a simplified food frequency questionnaire. Cognitive impairment was evaluated based on the Mini-Mental State Examination Scale combined with years of education. Fasting venous blood samples were collected to detect inflammatory markers, especially high-sensitivity C-reactive protein (hs-CRP) and the platelet-to-lymphocyte ratio (PLR). RRR analysis was used to obtain inflammation-related dietary patterns using hs-CRP and PLR as response variables. Multivariate logistic regression model was used to analyze the association between dietary pattern score and the risk for cognitive impairment. Restricted cubic spline was used to explore the dose response relationship, and mediation analysis was used to quantify the mediating effects of hs-CRP and PLR.Results:Two dietary patterns were identified with RRR. The primary pattern was characterized by higher intakes of flour, red meat, and dairy products, and lower intake of fresh vegetables, explaining 6.84% of the variance in food intake and 0.50% of the variance in inflammatory markers. Compared with the T1 group, the T3 group had significantly higher risk for cognitive impairment ( OR=1.242, 95% CI: 1.034-1.491). Each one standard deviation increase in the dietary pattern score was associated with an 8.7% increase in the risk for cognitive impairment ( OR=1.087, 95% CI: 1.008-1.172), with a significant linear trend (overall-model P<0.001, non-linear P=0.295). Mediation analysis indicated that hs-CRP mediated 6.2% of the association between the dietary pattern and the risk for cognitive impairment. Conclusion:The inflammation- related dietary pattern characterized by higher consumption of flour, red meat, and dairy products and lower consumption of fresh vegetables is associated with an increased risk for cognitive impairment in older adults, and hs-CRP partially mediates this association.

Objective:To explore the correlation between the level of T-lymphocyte subsets in peripheral blood and the progression of Alzheimer′s disease (AD).Methods:A cross-sectional study was conducted, including 30 cases of amnestic mild cognitive impairment (aMCI; aMCI group), 30 cases of mild AD (Mi-D; Mi-D group), 30 cases of moderate AD (Mo-D; Mo-D group), who were diagnosed in the Affiliated Hospital of Traditional Chinese Medicine of Xinjiang Medical University from January to December 2023, and 30 normal controls (normal control group) matched by age and gender. The levels of T cell subsets in peripheral blood were detected by flow cytometry, and the subpopulations of CD4 +T cells, Th cells, were examined. Binary Logistic regression was used to explore the correlation between factors affecting patients′ cognitive function and the onset of AD, and Spearman′s correlation analysis was applied to assess the association between the level of peripheral blood immune cells and the severity of AD. Results:There were no statistically significant differences in peripheral blood CD4 +T cells ( F=1.762, P=0.158), CD8 +T cells ( F=0.370, P=0.775), CD4 +/CD8 +ratios ( F=1.976, P=0.121), and regulatory T cells (Tregs) levels ( F=0.232, P=0.874) among the aMCI group, Mi-D group, Mo-D group, and normal control group in the intergroup comparisons (all P>0.05). The study subjects were stratified according to gender, age, body mass index, and years of education affecting the cognitive function of AD patients, and the peripheral blood CD4 +T cells, CD8 +T cells, CD4 +/CD8 + ratios and Tregs levels showed no statistically significant differences among groups (all P>0.05). The results of binary Logistic regression analysis showed that the peripheral blood CD8 +T-cell level ( OR=1.131, 95% CI 1.009-1.268, P=0.035) was a risk factor for the onset of AD. Further analysis of peripheral blood CD4 +T cell subsets revealed that Th1 cell levels were lower in the aMCI group compared to the Mi-D group ( t=-2.354, P=0.036), and the Mo-D group ( t=-2.079, P=0.026). The results of the Spearman′s correlation analysis showed that peripheral blood Th1 cell level was positively correlated with AD progression ( r=0.192, P<0.05). Conclusions:AD patients show peripheral immune imbalance, peripheral blood CD8 +T-cell level is a risk factor for the onset of AD, and peripheral Th1 cell level is positively correlated with the severity of AD. Monitoring the changes in peripheral blood Th1 cell level may have a predictive value for the progression of AD.

With the rapid advancement of artificial intelligence technology, chatbots have shown great potential in the healthcare sector. From personalized health advice to chronic disease management and psychological support, chatbots have demonstrated significant advantages in improving the efficiency and quality of healthcare services. As the scope of their applications expands, the relationship between technological complexity and practical application scenarios has become increasingly intertwined, necessitating a more comprehensive evaluation of both aspects. This paper, from the perspective of he althcare applications, systematically reviews the technological pathways and development of chatbots in the medical field, providing an in-depth analysis of their performance across various medical scenarios. It thoroughly examines the advantages and limitations of chatbots, aiming to offer theoretical support for future research and propose feasible recommendations for the broader adoption of chatbot technologies in healthcare.

BACKGROUND: Prospective evidence on how offspring number influences morbidity and mortality remains limited. This study investigated the associations between number of offspring and morbidity and mortality risks among 0.5 million Chinese adults. METHODS: By using data from the China Kadoorie Biobank (CKB; n = 512,723, an approximately 12-year follow-up), sex-stratified phenome-wide association study (PheWAS) analyses were conducted to investigate associations between offspring number (without vs . with offspring; more than one vs . one offspring) and risks of ICD10-coded morbidity and mortality. Sex-specific adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were estimated by Cox proportional-hazards models. RESULTS: Among 210,129 men and 302,284 women aged 30-79 years, 1,338,837 incident events were recorded. PheWAS results revealed that offspring number was associated with disease risks across multiple systems. Cox models showed that childless men ( vs . one offspring) had higher risks for nine of 36 diseases, while childless women for five of 37. Each additional offspring was associated with reduced risks of mental and behavioral disorders in men (aHR [95% CI] = 0.93 [0.87-0.98]) and both mental and behavioral disorders (aHR [95% CI] = 0.93 [0.89-0.97]) and breast cancer (aHR [95% CI] = 0.82 [0.78-0.86]) in women. However, each additional offspring was associated with a 4% increase in the risk of cholelithiasis and cholecystitis in women (aHR [95% CI] = 1.04 [1.02-1.07]). Among 282,630 patients, 44,533 deaths were documented. Childless patients had higher mortality risk in both men (aHR [95% CI] = 1.37 [1.28-1.47]) and women (aHR [95% CI] = 1.27 [1.15-1.41]). For men, each additional offspring reduced mortality by 4% (aHR [95% CI] = 0.96 [0.95-0.98]), while for women, the lowest risk was observed among those with three to four offspring ( Pnonlinear <0.0001). CONCLUSIONS Offspring number is closely linked to morbidity and mortality risks. Further research is warranted to verify our findings and clarify the underlying mechanisms involved.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; China/epidemiology* ; Morbidity ; Proportional Hazards Models ; Prospective Studies ; Risk Factors ; Family Characteristics ; Mortality ; East Asian People

Objective:To analyze the association between inflammation-related dietary patterns and the risk for cognitive impairment in older adults aged ≥65 years in longevity areas in China by using reduced rank regression (RRR) analysis.Methods:This study used cross-sectional data from the 2021 Healthy Aging and Biomarkers Cohort Study, including the information about study participants' demographic characteristics, lifestyles, daily life activities, and disease histories. Dietary intake was obtained by using a simplified food frequency questionnaire. Cognitive impairment was evaluated based on the Mini-Mental State Examination Scale combined with years of education. Fasting venous blood samples were collected to detect inflammatory markers, especially high-sensitivity C-reactive protein (hs-CRP) and the platelet-to-lymphocyte ratio (PLR). RRR analysis was used to obtain inflammation-related dietary patterns using hs-CRP and PLR as response variables. Multivariate logistic regression model was used to analyze the association between dietary pattern score and the risk for cognitive impairment. Restricted cubic spline was used to explore the dose response relationship, and mediation analysis was used to quantify the mediating effects of hs-CRP and PLR.Results:Two dietary patterns were identified with RRR. The primary pattern was characterized by higher intakes of flour, red meat, and dairy products, and lower intake of fresh vegetables, explaining 6.84% of the variance in food intake and 0.50% of the variance in inflammatory markers. Compared with the T1 group, the T3 group had significantly higher risk for cognitive impairment ( OR=1.242, 95% CI: 1.034-1.491). Each one standard deviation increase in the dietary pattern score was associated with an 8.7% increase in the risk for cognitive impairment ( OR=1.087, 95% CI: 1.008-1.172), with a significant linear trend (overall-model P<0.001, non-linear P=0.295). Mediation analysis indicated that hs-CRP mediated 6.2% of the association between the dietary pattern and the risk for cognitive impairment. Conclusion:The inflammation- related dietary pattern characterized by higher consumption of flour, red meat, and dairy products and lower consumption of fresh vegetables is associated with an increased risk for cognitive impairment in older adults, and hs-CRP partially mediates this association.