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.

Radical gastrectomy with D2 lymphadenectomy has been widely performed as the standard surgery for patients with gastric cancer in major medical centers in China and abroad. However, the exact extent of lymph node dissection is still controversial. In the latest version of the Japanese Gastric Cancer Treatment Guidelines, No. 14v lymph nodes (along the root of the superior mesenteric vein) are again defined as loco-regional lymph nodes, and it is clarified that distal gastric cancer presenting with infra-pyloric regional lymph node (No.6) metastasis is recommended for D2+ superior mesenteric vein (No. 14v) lymph node dissection. To explore the relevance and clinical significance of No.6 and No.14v lymphadenectomy in radical gastric cancer surgery, a review of the national and international literature revealed that No.6 lymph node metastasis was associated with No.14v lymph node metastasis, that No.6 lymph node status was a valid predictor of No.14v lymph node negative status and false negative rate, and that for gastric cancer patients with No. 14v lymph node negative and No.6 lymph node positive, the dissection of No.14v lymph node may also have some significance. The addition of No. 14v lymph node dissection in radical gastrectomy is safe, but it is more important to distinguish the patients who can benefit from it. Professor Liang Han of Tianjin Medical University Cancer Hospital is currently leading a multicenter, large-sample, prospective clinical trial (NCT02272894) in China, which is expected to provide higher level evidence for the clinical significance of lymph node dissection in No.14v.
Humans ; Stomach Neoplasms/pathology* ; Lymphatic Metastasis/pathology* ; Prospective Studies ; Retrospective Studies ; Lymph Nodes/pathology* ; Lymph Node Excision ; Gastrectomy ; Multicenter Studies as Topic

Objective: To investigate the clinicopathological characteristics of malignant gastrointestinal neuroectodermal tumors (GNET), and to describe their clinical, histological, immunophenotypic, ultrastructural, and molecular features, diagnosis and differential diagnosis. Methods: Three cases of malignant GNET were collected at Xijing Hospital of the Fourth Military Medical University, from 2013 to 2022. All patients underwent surgical resection of the tumor. Histological, immunohistochemical (IHC), ultrastructural and molecular genetic analyses were performed, and the patients were followed up for six months, three years and five years. Results: There were two males and one female patients. The tumors were located in the ileum, descending colon, and rectum, respectively. Grossly, the tumors were solid, firm, and poorly circumscribed, measured in size from 2 to 4 cm in greatest dimension, and had a greyish-white cut surface. These tumors were histologically characterized by a sheet-like or nested population of oval to spindled cells or epithelioid cells with weakly eosinophilic or clear cytoplasm, small nucleoli and scattered mitoses. Electron microscopy showed neuroendocrine differentiation, and no evidence of melanogenesis. IHC staining showed that the tumor cells were diffusely positive for S-100 protein, SOX10, CD56, synaptophysin and vimentin. They were negative for melanocytic markers, HMB45 and Melan A. All three cases showed split EWSR1 signals consistent with a chromosomal translocation involving EWSR1. Next-generation sequencing in one case confirmed the presence of EWSR1-ATF1 fusion. These patients were followed up for 6 months, 3 years and 5 years, respectively, and all of them developed possible lung or liver metastases, and one of them died of multiple pulmonary metastases. Conclusion: Malignant GNET has distinctive morphological, IHC, and molecular genetic features and it should be differentiated from other malignancies of the gastrointestinal tract, especially clear cell sarcoma and melanoma.
Male ; Humans ; Female ; Biomarkers, Tumor/analysis* ; Gastrointestinal Neoplasms/pathology* ; S100 Proteins/analysis* ; Melanoma

Objective: To investigate the association between the distribution of tumor infiltrating lymphocytes (TIL) in EBV associated lymphoepitheliomatoid carcinoma (LELC) and the pathological subtypes of LELC, as well as the clinical significance of TIL distribution. Methods: The LELC patients with sufficient tumor tissues, complete clinical data and positive EBER, who visited Zhejiang Cancer Hospital, Hangzhou, China from January 2006 to October 2018, were selected. Various immunohistochemical markers (CD20, CD138, CD4, CD8, CD56 and FOXP3) were examined for TIL typing. Two pathologists reviewed the hematoxylin and eosin (HE) staining sections and interpreted the immunohistochemical results. Correlation analysis was used to evaluate the relationship between the distribution of TIL subgroups and LELC's pathological characteristics. Survival analyses were conducted to study the prognostic values of TIL subgrouping. Results: A total of 102 patients with EBV related LELC were included. 46 of them were classic LELC (c-LELC) with rich interstitial TIL, and 56 were non-classic LELC (n-LELC) with relatively fewer interstitial TIL. The results of TIL analysis showed that all subtypes of c-LELC were rich in TIL, with B lymphocytes as the dominant subgroup. The number of TIL in n-LELC was fewer than that in c-LELC, with T lymphocytes as the dominant subgroup. There was no significant difference in the distribution of plasma cells between the two groups. Survival analysis showed that the total number of TIL, and the infiltrations of CD20⁺B cells, CD4⁺T cells, and FOXP3⁺Treg cells were associated with better overall survivals (P=0.004, 0.003, 0.008 and 0.025, respectively) and disease-free survivals (P=0.011, 0.003, 0.038 and 0.041, respectively) in patients with LELC. Conclusions: The morphologic subtypes of EBV-related LELC have different tumor immune characteristics. The total number of TIL in the stroma of c-LELC is significantly higher than that of n-LELC. Interestingly, B lymphocytes are the dominant TIL in c-LELC, while T lymphocytes are the dominant TIL in n-LELC. The infiltration of TIL, CD20⁺B cells, CD4⁺T cells and FOXP3⁺Treg cells in LELC may suggest a better prognosis.
Humans ; Lymphocytes, Tumor-Infiltrating ; Herpesvirus 4, Human ; Clinical Relevance ; Prognosis ; Carcinoma, Squamous Cell/pathology* ; Forkhead Transcription Factors

OBJECTIVE: To evaluate the molluscicidal activity of surfactin against Oncomelania hupensis, so as to provide the experimental basis for use of Bacillus for killing O. hupensis. METHODS: O. hupensis snails were collected from schistosomiasisendemic foci of Wuhu City on September 2022, and Schistosoma japonicum-infected snails were removed. Then, 60 snails were immersed in surfactin at concentrations of 2, 1, 0.5, 0.25, 0.125 mg/mL and 0.062 5 mg/mL for 24, 48, 72 hours at 26 °C, while ultrapure water-treated snails served as controls. The median lethal concentration (LC₅₀) of surfactin against O. hupensis snails was estimated. O. hupensis snails were immersed in surfactin at a concentration of 24 h LC₅₀ and ultrapure water, and then stained with propidium iodide (PI). The PI uptake in haemocyte was observed in O. hupensis snails using fluorescence microscopy. RESULTS: The mortality of O. hupensis was 5.0% following immersion in surfactin at a concentration of 0.062 5 mg/mL for 24 h, and the mortality was 100.0% following immersion in surfactin at a concentration of 2 mg/mL for 72 h, while no snail mortality was observed in the control group. There were significant differences in the mortality of O. hupensis in each surfactin treatment groups at 24 (χ² = 180.150, P < 0.05), 48 h (χ² = 176.786, P < 0.05) and 72 h (χ² = 216.487, P < 0.05), respectively. The average mortality rates of O. hupensis were 38.9% (140/360), 62.2% (224/360) and 83.3% (300/360) 24, 48 h and 72 h post-immersion in surfactin, respectively (χ² = 150.264, P < 0.05), and the 24, 48 h and 72 h LC₅₀ values of surfactin were 0.591, 0.191 mg/mL and 0.054 mg/mL against O. hupensis snails. Fluorescence microscopy showed more numbers of haemocytes with PI uptake in 0.5 mg/mL surfactintreated O. hupensis snails than in ultrapure water-treated snails for 24 h, and there was a significant difference in the proportion of PI uptake in haemocytes between surfactin-and ultrapure water-treated snails (χ² = 6.690, P < 0.05). CONCLUSIONS Surfactin is active against O. hupensis snails, which may be associated with the alteration in the integrity of haemocyte membrane.
Animals ; Molluscacides/pharmacology* ; Snails ; Schistosoma japonicum ; Lethal Dose 50 ; Water

Humans ; Osteogenesis ; Mesentery/surgery* ; Ossification, Heterotopic/surgery*

Under the new situation of professionalization reform for fire rescue forces in China, the research on post-traumatic stress disorder (PTSD) of the emergency rescue personnel is expected to usher in a new stage. Based on some theoretical researches and practical results of domestic and foreign literature, this paper summarized the research results of the social and psychological factors of PTSD of emergency rescue personnel, and made suggestions and prospects for the future research and policy-making in related fields in China.
China ; Emergency Service, Hospital ; Humans ; Occupations ; Stress Disorders, Post-Traumatic

Coal ; Coal Mining ; Dust/analysis* ; Humans ; Male ; Miners ; Occupational Diseases ; Occupational Exposure/adverse effects*

Precision medicine became the key strategy in development priority of science and technology in China. The large population-based cohorts become valuable resources in preventing and treating major diseases in the population, which can contribute scientific evidence for personalized treatment and precise prevention. The fundamental question of the achievements above, therefore, is how to construct a large population-based cohort in a standardized way. The Chinese Preventive Medicine Association co-ordinated experienced researchers from Peking University and other well-known institutes to write up two group standards Technical specification of data processing for large population-based cohort study (T/CPMA 001-2018) and Technical specification of data security for large population-based cohort study (T/CPMA 002-2018), on data management. The standards are drafted with principles of emphasizing their scientific, normative, feasible, and generalizable nature. In these two standards, the key principles are proposed, and technical specifications are recommended in data standardization, cleansing, quality control, data integration, data privacy protection, and database security and stability management in large cohort studies. The standards aim to guide the large population-based cohorts that have been or intended to be established in China, including national cohorts, regional population cohorts, and special population cohorts, hence, to improve domestic scientific research level and the international influence, and to support decision-making and practice of disease prevention and control.
China ; Cohort Studies ; Delivery of Health Care ; Humans ; Population Surveillance ; Quality Control ; Reference Standards

Objective: To understand the characteristics on major strain subtypes of hepatitis C virus among HIV/HCV co-infected patients, so as to explore the molecular transmission clusters and related risk factors of HCV strains. Methods: A total of 336 newly reported HIV-infected patients were diagnosed as HIV/HCV co-infection in Dehong Dai and Jingpo autonomous prefecture (Dehong) in 2016. We used Nested PCR to amplify CE1 and NS5B genes among 318 samples with plasma levels above 200 μl, before using the combining phylogenetic tree and constructing molecular propagation network method to analyze the related data. Results: A total of 267 HIV/HCV co-infection patients who had met the HCV genotyping requirements were screened the gene subtypes were diversified. Among these genotypes, proportions of 3b, 6n, 6u, 1a, 3a and other subtypes appeared as 32.6% (87/267), 18.4% (49/267), 15.7%(42/267), 13.1%(35/267), 11.2%(30/267) and 9.0%(24/267) respectively. Molecular transmission network of five major HCV genotypes was constructed with a clustering rate of 39.1% (95/243). The clustering rate of subtype 1a was the highest, as 71.4% (25/35). Results from the multivariate logistic regression showed that ethnic minorities other than the Yi and Jingpo (vs. the Han, OR=0.17, 95%CI: 0.04-0.71), the married spouses (vs. the unmarried, OR=0.42, 95%CI: 0.18-0.94), the 6n and 3a subtype (vs. the 3b subtype, OR=0.34, 95%CI: 0.12-0.95; OR=0.22, 95%CI: 0.05-0.93) were more difficult to form transmission clusters. However, the 6u and 1a subtype (vs. the 3b subtype, OR=3.10, 95%CI: 1.21-7.94; OR=4.00, 95%CI: 1.32-12.11) seemed more likely to form the transmission clusters. Conclusion: Ethnicity, marital status and genetic subtypes were factors significantly associated with the formation of transmission clusters related to the major HCV gene subtypes among newly reported HIV/HCV co-infection in Dehong.
AIDS-Related Opportunistic Infections/virology* ; Asian People ; China/epidemiology* ; Coinfection ; Genotype ; HIV Infections/virology* ; Hepacivirus/isolation & purification* ; Hepatitis C/virology* ; Humans ; Phylogeny ; Polymerase Chain Reaction