Delirium is a common cause and complication of hospitalization in the elderly and is associated with higher risk of future dementia and progression of existing dementia, of which 70% is Alzheimer's disease (AD). AD and delirium, which are known to be aggravated by one another, represent significant societal challenges, especially in light of the absence of effective treatments. The intricate biological mechanisms have led to numerous clinical trial setbacks and likely contribute to the limited efficacy of existing therapeutics. Artificial intelligence (AI) presents a promising avenue for overcoming these hurdles by deploying algorithms to uncover hidden patterns across diverse data types. This review explores the pivotal role of AI in revolutionizing drug discovery for AD and delirium from target identification to the development of small molecule and protein-based therapies. Recent advances in deep learning, particularly in accurate protein structure prediction, are facilitating novel approaches to drug design and expediting the discovery pipeline for biological and small molecule therapeutics. This review concludes with an appraisal of current achievements and limitations, and touches on prospects for the use of AI in advancing drug discovery in AD and delirium, emphasizing its transformative potential in addressing these two and possibly other neurodegenerative conditions.

Objective To investigate the effects of targeted silencing of CXCL5 on the related biological functions of laryngeal squamous cell carcinoma(LSCC)cell line AMC-HN-8,and analyze the regulation through TCGA database.Methods RNA-seq data related to LSCC were obtained from TCGA database,and the expression differences of CXCL5 gene in LSCC and the adjacent tissues were analyzed. Total 60 samples of LSCC and the adjacent tissues from January 2019 to December 2020 were selected from the First Hospital of Shanxi Medical University,and the expression of CXCL5 protein in LSCC tissues was detected by immunohistochemical staining. Human LSCC cell line AMC-HN-8 was cultured and the mRNA transcription level of CXCL5 in AMC-HN-8 cells was detected by qPCR. Two groups of SiRNA with high knock-down efficiency were screened,CCK8 assay was used to detect the cell proliferation,Transwell test was used to measure the cell invasion and migration,and flow cytometry was used to detect the cell cycle and apoptosis. The correlation between CXCL5and tumor immune invasion level of LSCC was analyzed by ssGSEA,and CXCL5 co-expression gene network was constructed and analyzed for GO and KEGG enrichment.Results Compared with the adjacent tissues and the cells in control group,the expression of CXCL5 in LSCC tissues and cells increased,which was consistent with the analysis of TCGA database;Inhibition of CXCL5 expression in AMC-HN-8 cells inhibited the proliferation,invasion and migration of tumor cells,and promoted the apoptosis through inhibiting the cell cycle in G1 phase;The immune cell scores in DC,neutrophils,NK and TH17 cells were different.Conclusion CXCL5gene is highly expressed in LSCC tissues,which might be one of the targets of LSCC targeted therapy.

Objective:To evaluate the clinical value of the adjusted global antiphospholipid syndrome score (aGAPSS) in patients with persistent antiphospholipid antibodies (aPL).Methods:The clinical data of patients who were continuously positive for aPL from May 2012 to August 2022 were retrospectively analyzed, except for patients complicated with connective tissue diseases. Demographic data, traditional cardiovascular thrombosis risk factors, aPL profile, and clinical manifestations included and not included in antiphospholipid syndrome (APS) were collected, and aGAPSS was calculated for all patients according to risk indicators and the correlation with clinical manifestation was analyzed through rank sum test. The diagnostic value of aGAPSS for different clinical manifestations was evaluated by the receiver operator characteristic (ROC) curve.Results:A total of 67 patients with persistent aPL were enrolled, including 15 patients with persistent extra-criteria positive aPL but did not meet the APS classification criteria and 52 patients with a clear diagnosis of primary APS, of which 20 had a history of thrombosis, 36 had a history of pregnancy morbidity, and 24 had extra-criteria clinical manifestations. Patients with history of any thrombosis or arterial thrombosis scored significantly higher than those with no history of thrombosis [any history of thrombosis 11.50 (8.25, 13.00) vs 8.00 (4.00, 13.00), Z=2.33, P=0.020; arterial thrombosis history 11.00 (9.00, 14.00) vs 8.00 (4.00, 13.00), H=6.21, P=0.043]. The aGAPSS score of patients with extra-criteria clinical manifestations was significantly higher than that of patients without corresponding clinical manifestations [13.00 (8.25, 13.00) vs 8.00 (4.00, 11.00), Z=2.81, P=0.005], and the aGAPSS score of patients with thrombocytopenia was significantly higher than that of patients without thrombocytopenia [12.50 (8.00, 13.25) vs 8.00 (4.00, 13.00), Z=2.23, P=0.026]. A subgroup analysis of pregnant women found no statistically significant difference in aGAPSS scores between groups with or without a history of pregnancy morbidity. With thrombosis as the endpoint event, aGAPSS had the highest diagnostic value at 10 points(sensitivity and specificity were 65.00% and 77.78%, respectively). Conclusion:In patients with postivity aPL positivity, aGAPSS score is correlated with thrombosis history and extra-criteria clinical manifestations, especially thrombocytopenia.

Objective:Analyze the impact of smoking on the mortality and life expectancy of residents in Tianjin in 2019.Methods:Use mortality case-control study method to collect all cause of death cases of residents in Tianjin in 2019 for analysis. After adjusting for the 5-years-old age group, education level, and marital status, the smoking attributed deaths from different diseases of different genders, smoking attributed deaths in different age groups, and their impact on life expectancy were analyzed.Results:The total number of deaths in 2019 was 75 254, with 42 201 males (56.1%). Among male deaths, 3 215 (9.9%) were attributed to smoking, of which 2 157 (50.2%) lung cancer deaths were attributed to smoking; The risk of lung cancer death among smokers was 3.075 times higher than that of non-smokers (95% CI: 2.812-3.364); Among the 33 053 female deaths (43.9%), 1 396 (5.8%) were caused by smoking, with 744 (29.1%) lung cancer deaths attributed to smoking. The age group with the highest number of deaths attributed to smoking for women was the 75-<80 years old age group, followed by the 70-<75 and 80-<85 years old age groups. The age group with the highest proportion of deaths attributed to smoking for men was the 55-<60 years old age group. In addition, smoking accounts for more than 60% of deaths in the 60-<65, 45-<50, 55-<60, and 65-<70 years old age groups. In 2019, the loss of life expectancy attributed to smoking deaths among all residents in Tianjin was 1.13 years, with a loss of 1.15 years for males and 0.57 years for females. The expected life expectancy excluding deaths caused by smoking was 82.92 years, 80.77 years for males and 84.61 years for females. Conclusions:Smoking remains one of the important risk factors for death among residents. Promoting effective measures to reduce smoking rates is an effective way to increase life expectancy.

Humans ; Nitric Oxide ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Lung Neoplasms ; Lung ; Nitric Oxide Synthase ; Macrophages, Alveolar ; Pulmonary Alveoli

BACKGROUND: The switch/sucrose nonfermentable chromatin-remodeling (SWI/SNF) complex is a pivotal chromatin remodeling complex, and the genomic alterations (GAs) of the SWI/SNF complex are observed in several cancer types, correlating with multiple biological features of tumor cells. However, their role in liver metastasis of non-small cell lung cancer (NSCLC) remains unclear. Our study aims to investigate the role and potential mechanisms underlying NSCLC liver metastasis induced by the GAs of SWI/SNF complex. METHODS: The GAs of SWI/SNF complex in NSCLC cell lines (H1299, H23 and H460) were identified by whole-exome sequencing (WES). ARID1A knockout H1299 cell was constructed with the CRISPR/Cas9 technology. The mouse model of liver metastasis from NSCLC was established to simulate lung cancer liver metastasis and observe the metastasis rate under different gene mutation conditions. RNA sequencing and Western blot were conducted for differential gene expression analysis. Immunohistochemistry (IHC) analysis was used to assess protein expression levels of SWI/SNF-regulated target molecules in mouse liver metastases. RESULTS: WES analysis revealed intracellular gene mutations. The animal experiments demonstrated a correlation between the GAs of SWI/SNF complex and a higher liver metastasis rate in immunodeficient mice. Transcriptome sequencing and Western blot analysis showed upregulated expression of ALDH1A1 and APOBEC3B in SWI/SNF-mut cells, particularly in ARID1A-deficient H460 and H1299 sgARID1A cells. IHC staining of mouse liver metastases further demonstrated elevated expression of ALDH1A1 in the H460 and H1299 sgARID1A group. CONCLUSIONS This study underscores the critical role of the GAs of SWI/SNF complex, such as ARID1A and SMARCA4, in promoting liver metastasis of lung cancer cells. The GAs of SWI/SNF complex may promote liver-specific metastasis by upregulating ALDH1A1 and APOBEC3B expression, providing novel insights into the molecular mechanisms underlying lung cancer liver metastasis.
Animals ; Mice ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Liver Neoplasms/genetics*

Objective:To investigate the genetic safety of allogeneic bone marrow mesenchymal stem cells (BMSCs) transplantation in traumatic brain injury (TBI).Methods:(1) In vivo experiment: BMSCs from male SD rats were isolated and cultured. Moderate TBI models were prepared by implanting and fixing micro-drug injection cannula into the left ventricle of 12 female SD rats, and 3 d after that, striking the right cerebral cortex of the rats with pneumatic precision percussion device was performed. Four h, and 3, 6, 9, and 12 d after modeling, TBI rats were given a single/multiple BMSCs infusion (2.5×10 5/time, total volume 10 μL) by cannula; 48 and 72 h, and 10 and 14 d after modeling, brain tissues of TBI rats (3 at each time point) were prepared into paraffin specimens. Immunofluorescent staining was used to detect the microglia activation, and RNAscope ? technology was used to detect the co-localization of astrocytes, neurons, microglia and transplanted BMSCs to observe whether the allogeneic BMSCs were integrated with the host brain cells after transplantation into TBI host. (2) In vitro experiment: the frozen and revived microglial cell line BV2 was transfected with green fluorescent protein (GFP)-positive lentiviral particles, and then, BMSCs prelabeled with pHrodo RED probe and BV2 cells pretreated with lipopolysaccharide were co-cultured in a certain ratio (BV2:BMSCs=1:1, 1:2, 2:1); after 36 and 72 h of co-culture, the phagocytosis between the 2 kinds of cells was observed under confocal fluorescence inverted microscope to observe the specific action forms of microglia on BMSCs. Results:(1) In vivo experiment: 48 and 72 h, and 10 and 14 d after modeling, no colocalization of transplanted BMSCs with astrocytes or neurons was found in paraffin sections of brain tissue in TBI rats; however, 10 and 14 d after modeling, microglia in TBI rats were obviously activated and migrated to the left lateral ventricle and choroid plexus, and co-localization of microglia with transplanted BMSCs was observed. (2) In vitro experiment: phagocytosis occurred after co-culture of BV2 cells at different proportions with BMSCs for 36 and 72 h. Conclusion:After transplantation, allogeneic BMSCs do not integrate with astrocytes or neurons of the TBI host, but they could be phagocytosed by microglia, indicating that allogeneic BMSCs transplantation for TBI is genetically safe.

In the USA, there were about 1 ‍806 ‍590 new cancer cases in 2020, and 606 520 cancer deaths are expected to have occurred in 2021. Lung cancer has become the leading cause of death from cancer in both men and women (Siegel et al., 2020). Clinical studies show that the five-year survival rate of lung cancer patients after early diagnosis and treatment intervention can reach 80%, compared with that of patients having advanced lung cancer. Thus, the early diagnosis of lung cancer is a key factor to reduce mortality.
Male ; Humans ; Female ; Tomography, X-Ray Computed/methods* ; Algorithms ; Lung Neoplasms/pathology* ; Cluster Analysis

Objective: To establish the norms and clinical application standards of mass spectrometry method to measure vitamin D in capillary blood. Methods: Following the "Province-City-Hospital" sampling procedure, a cross-sectional sample of 1 655 healthy children under 7 years of age were recruited from 12 provinces, autonomous regions, or municipalities in China from November 2020 to December 2021. Both venous and capillary blood samples from the same individual were collected, for which serum 25(OH)D levels were measured by high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method. Pearson correlation analysis and linear regression analysis were used to detect the correlation and determine a correction algorithm. The agreement was analyzed using Bland-Altman plot and Kappa statistic. The sensitivity and specificity were evaluated using receiver operating characteristic (ROC) curve method. Results: Venous and capillary 25(OH)D levels of 1 655 healthy children under 7 years of age were 74.25 (59.50, 92.00) and 68.75 (54.44, 86.25) nmol/L, respectively, showed a significant difference(Z=22.14, P<0.001) as well as a highly significant correlation between venous and capillary 25(OH)D levels(r=0.95, P<0.001). Linear regression analysis was then performed to determine the correction algorithm: lg(corrected capillary 25(OH)D)=0.13+0.95×lg(capillary 25(OH)D)(R²=0.90,P<0.001). The deviation between venous and corrected capillary 25(OH)D levels was (0.50±17.50) nmol/L, a difference value that did not reach statistical significance (P>0.05). The cut-off values of capillary blood 25(OH)D values 30.00, 50.00, 75.00 nmol/L corresponding to venous blood 25(OH)D values were 26.59, 45.56, and 69.84 nmol/L, respectively. Good consistency was observed between venous and corrected capillary 25(OH)D levels in clinical diagnosis (Kappa value 0.68-0.81). Corrected capillary 25(OH)D showed a high clinically predictive value (area under curve 0.97-0.99,sensitivity 0.72-0.92,specificity 0.89-0.99). Conclusion: The standardized capillary HPLC-MS/MS method can be used to detect 25(OH)D levels in children clinically.
Child ; Humans ; Vitamin D ; Cross-Sectional Studies ; Tandem Mass Spectrometry ; Vitamins ; Reference Standards

【Objective】 To investigate and analyze the polymorphism of RHD gene in RhD-negative population in Jiayuguan using molecular biological technique, so as to accurately identify RhD-negative individuals, and formulate individualized transfusion strategies. 【Methods】 The RhD negative voluntary blood donors and patients (mainly pregnant women) were recruited. After informed consent, history of blood transfusion and pregnancy of them were investigated, and samples were collected for negative D confirmation, gene sequencing as well as antibody screening and identification. 【Results】 Among the 96 samples, 73 cases were RHD gene deletion, 18 RHD^*01EL.01(17 RHD1227A homozygous type and 1 RHD1227A heterozygous type), 2 weak RHD^*15 type (845G/A), 1 partial D type, i. e. RHD-CE(7) -D heterozygous allele, and 2 RHD^*01N.16 variant. Antibody was detected out in 4 cases, among which 2 were positive for anti-D, 1 anti-D plus anti-E, and 1 anti-Di^a. 【Conclusion】 The proportion of DEL gene in RhD negative Chinese Han population in Jiayuguan is slightly lower than that in general Chinese Han population. No anti-D or RHD-HDN was observed in DEL type women due to multiple pregnancy or delivery of D positive newborns.