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 plateau hypoxia on the growth and tumor microenvironment of colorectal carcinoma in vivo.Methods A total of 16 male BALB/C mice(6 weeks old,weight 18-20 g)were randomly divided into plateau hypoxic group and plain normoxic group,with 8 mice in each group,while 14 male C57BL/6 mice were grouped in same way,with 7 mice in each group.The mice in the plateau hypoxic group were housed in a low-pressure oxygen(10%)chamber to simulate an altitude of approximately 5 600 m,while the mice of the other group was maintained in SPF-grade normal atmospheric conditions(21%oxygen,at an altitude of about 300 m).Colorectal tumor MC38 cells and colon adenocarcinoma CT26 cells were subcutaneously implanted into C57BL/6 mice and BALB/C mice,respectively to construct subcutaneous tumor-bearing mouse models.Then the tumor size and weight were measured in 4 groups of mice.After the tumor tissues,spleen and blood samples were collected in the C57BL/6 mice.Flow cytometry was used to determine the percentages of macrophages,T lymphocytes,IFN-γ+T lymphocytes,and myeloid-derived suppressor cells(MDSC).The differences in these immune cells were compared between the cells from the plateau hypoxic group and those from the plain normoxic group.Results The weight of subcutaneous tumor mass was significantly inhibited in both C57BL/6 and BALB/C mice from the plateau hypoxic group than those from the 2 plain normoxic groups(0.17 vs 0.09 g,1.38 vs 0.51 g,P<0.01).When compared with the immune cells from the tumor mass of the plain normoxic C57BL/6 mice,the percentage of M2-type macrophages was reduced in the tumor tissue from the plateau hypoxic mice(22.13%vs 15.90%,P<0.05),so was that of MDSC(2.06%vs 1.05%,P<0.01),particularly in the monocytic(M)-MDSC subgroup(60.97%vs 41.13%,P<0.01).While,no significant change was observed in the proportion of the polymorphonuclear(PMN)-MDSC subgroup(10.97%vs 9.70%,P>0.05).Additionally,the percentage of CD4+T cells was significantly reduced(48.70%vs 41.93%,P<0.05),whereas that of CD8+T cells was obviously increased(41.25%vs 51.18%,P<0.05),along with a notable rise in the proportions of IFN-γ+T,IFN-γ+CD4+T and IFN-γ+CD8+T cells(28.58%vs 59.65%,23.33%vs 53.65%,36.9%vs 66.48%,P<0.01).However,between the peripheral blood samples of the 2 groups of C57BL/6 mice,the proportions of M1-type macrophages and CD4+T cells were reduced(84.98%vs 78.43%,5.86%vs 4.01%,P<0.01),and those of MDSC and PMN-MDC were increased(4.47%vs 16.43%,36.56%vs 62.97%,P<0.01).In the spleen tissues,notable decreases were observed in the proportions of CD8+T cells and IFN-γ+CD8+T cells between the 2 groups(33.05%vs 27.68%,5.13%vs 1.58%,P<0.01).Conclusion Plateau hypoxia improves the immune response within the tumor microenvironment,and inhibits subcutaneous tumor growth of colorectal cancer,but suppresses systemic immune response.

Objective To explore the clinical application value of simple artery occlusion (SAO) in revealing intersegmental planes during thoracoscopic pulmonary segmentectomy. Methods A retrospective analysis was conducted on the clinical data of patients who underwent thoracoscopic pulmonary segmentectomy at the First Affiliated Hospital of Xiamen University from February 2022 to December 2023. Patients were divided into a conventional group and a SAO group based on the method used to reveal the intersegmental plane during surgery. The two groups were compared in terms of intraoperative blood loss, operation time, postoperative drainage volume, time to intubation, postoperative pulmonary air leakage, and conversion to open thoracotomy rate. Results A total of 318 patients were included. There were 181 patients in the conventional group, including 86 males and 95 females, with an average age (53.35±9.20) years, and there were 137 patients in the SAO group, including 58 males and 79 females, with an average age (55.26±11.46) years. There were no statistical differences in general patient information between the two groups (P>0.05). The SAO group had less intraoperative blood loss [MD=17.568, 95%CI (9.968, 25.168), P<0.001] and postoperative drainage volume [MD=275.587, 95%CI (188.999, 362.175), P<0.001], shorter drainage tube duration [MD=1.000, 95%CI (1.000, 2.000), P<0.001] and operation time [MD=20.709, 95%CI (16.258, 25.159), P<0.001]. The incidence of postoperative pulmonary air leakage complications in the SAO group was lower than that in the conventional group [RR=0.361, 95%CI (0.181, 0.722), P=0.003]. Conclusion SAO can reduce surgical difficulty, shorten operation time, decrease the incidence of postoperative pulmonary air leakage, and enhance the safety of anatomical pulmonary segmentectomy, making it worthy of clinical promotion and application.

Following the rapid advancement of artificial intelligence technologies, especially the development of large language models like ChatGPT, the field of medical clinical practice is undergoing an unprecedented technological revolution. These advanced technologies, through efficient processing and analysis of large datasets, not only provide medical professionals with auxiliary diagnoses and treatment suggestions but also significantly enhance the quality and efficiency of medical education. This study conducts a comprehensive analysis and review of the applications of large language models in various aspects, including clinical inquiry, history collection, medical literature writing, clinical decision support, optimization of medical portal websites, patient health management, medical education, academic research, and scientific writing. However, the application of these technologies is not without flaws and presents several limitations and ethical challenges. This paper focuses on challenges related to technological errors, academic dishonesty, abuse risks, over-reliance, possibilities of misdiagnosis and treatment errors, and issues of accountability. In conclusion, large language models demonstrate tremendous potential in the integration and advancement of medical practices. Nevertheless, while fully harnessing the benefits brought by ChatGPT, it is essential to acknowledge and address these ethical challenges to ensure that the application of ChatGPT in the medical field is responsible and effective.

Objective To investigate the impact of anti-reflux modified duodenal exclusion surgery on glucose metabolism in rats with type 2 diabetes mellitus (T2DM), and to elucidate the role of the duodenum in maintaining glucose homeostasis. MethodsForty male Sprague-Dawley rats aged 5 weeks were fed a high-fat diet and induced with T2DM using low-dose streptozotocin. Thirty-six rats that met the T2DM model criteria were randomly divided into three groups: the simple duodenal exclusion surgery group (DE group), the anti-reflux modified duodenal exclusion group (MDE group), and the sham operation group (SO group), with 12 rats in each group. Gastroenterography was performed 4 weeks after surgery, and the body weight, fasting blood glucose levels, and serum glucagon-like peptide-1 (GLP-1) concentrations were measured before surgery and at 1, 2, 4, and 8 weeks post-surgery. Eight weeks post-surgery, the rats were euthanized, and a 1 cm segment of the biliopancreatic loop was collected from each group for pathological sectioning and HE staining to observe the intestinal mucosal villus length under an optical microscope. Results Gastroenterography showed that there was significant reflux of the contrast agent into the duodenal lumen in the DE group, while no reflux was observed in the MDE group. At one week post-surgery, the body weights of rats in all three groups significantly decreased compared to before surgery (P<0.05), and then the body weights of all groups increased over time, with no significant differences between the groups (P>0.05). Compared with the SO group, the fasting blood glucose levels in the MDE and DE groups significantly decreased at all time points post-surgery (P<0.05), while GLP-1 concentrations significantly increased (P<0.05). The fasting blood glucose levels in the MDE group were lower than those in the DE group at all time points post-surgery (P<0.05), but there were no significant differences in serum GLP-1 concentrations between the MDE and DE groups (P>0.05). Regarding intestinal mucosal morphology, the villus lengths of the biliopancreatic loops in the MDE group were significantly shorter than those in the DE and SO groups (P<0.05). Conclusion Anti-reflux modified duodenal exclusion surgery effectively improves glucose metabolism in T2DM rats by preventing the reflux of chyme into the diverted duodenum, thereby enhancing its hypoglycemic effect.

Lung cancer is a disease with high incidence rate and high mortality rate worldwide. Its diagnosis and treatment mode is developing constantly. Among them, multi-disciplinary team (MDT) can provide more accurate diagnosis and more individualized treatment, which can not only benefit more early patients, but also prolong the survival time of late patients. However, MDT diagnosis and treatment mode is only carried out more in provincial and municipal tertiary hospitals and has not been popularized. This article intends to introduce MDT mode and its advantages, hoping that MDT mode can be popularized and applied.

Objective To explore the effectiveness and compliance of ketogenic-diet(KD) treatment for infantile spasm(IS).Methods Ninety-eight IS patients who were treated with KD in Wuhan Children's Hospital from March 2009 to June 2015 were analyzed by using retrospective case-control study,the patients were divided into 4 groups:newly diagnosed IS patients group (group A,including 24 patients),one antiepileptic drug (AEDs) failure IS patients (group B,including 28 patients),two and more AEDs failure IS patients (group C,including 29 patients),and two or more AEDs combined with ACTH failure IS patients(group D,including 17 patients).The spasm-free andretention rates after 3,6 and 12 months KD treatment were compared among these groups.Results Overall retention rate was 80.6％ (79/98 cases),69.4％ (68/98 cases),and 42.9％ (42/98 cases)at 3,6,12 months,respectively.The 3-month retention rate in group A,B,C and D was 83.3 ％ (20/24 cases),78.6％ (22/28 cases),82.7％ (24/29 cases) and 76.4％ (13/17 cases) respectively,and there was no significant difference among these groups (P ＞ 0.05).The 6-month retention rates in each group was 75.0％ (18/24 cases),67.9％ (19/28 cases),68.8％ (20/29 cases) and 65.0％ (11/17 cases) in sequence,and there was also no significant difference among these groups(P ＞0.05).The 12-month retention rate was 54.2％ (13/24 cases),21.4％ (6/28 cases),48.3％ (14/29 cases) and 52.9％ (9/17 cases) in group A,B,C and D in sequence,the 12-month retention rate of group B was significantly lower than that of other 3 groups,and the differences were statistically significant(x2 =5.973,4.508,4.727,all P ＜ 0.05),and there was no significant difference among the A,C,D groups (all P ＞ 0.05).The spasm-free rate at 3,6,12 months of KD treatment was 19.4％ (19/98 cases),20.4％ (20/98 cases),30.6％ (30/98 cases).The 3-month spasm-free rate in A,B,C,D groups were as follow:41.7％ (10/24 cases),14.3％ (4/28 cases),10.3％ (3/29 cases),11.8％ (2/17 cases),respectively.The 3-month spasm-free rate in group A was significantly higher than that of other 3 groups,and the differences were statistically significant (x2 =10.238,9.219,6.697,all P ＜ 0.05),but there was no significant difference among the B,C,D groups (all P ＞ 0.05).The 6-month spasm-free rates were 41.7％ (10/24 cases),14.3％ (4/28 cases),13.8％ (4/29 cases),and 11.8％ (2/17 cases) in group A,B,C and D in order,and the spasm-free rate in group A was significantly higher than that of other 3 groups,and the differences were statistically significant(x2 =4.924,5.249,4.298,all P ＜ 0.05),but there was no significant difference among the A,C,D groups (all P ＞ 0.05).The 12-month spasm-free rates were 54.2％ (13/24 cases),21.4％ (6/28 cases),24.1％ (7/29 cases),and 23.5 ％ (4/17 cases) in group A,B,C and D,and the spasm-free rate in group A was significantly higher than that in other 3 groups,and the differences were statistically significant(x2 =8.354,7.923,4.364,all P ＜ 0.05),but there was no significant difference among the A,C,D groups (all P ＞ 0.05).Conclusions The spasm-free rate of KD therapy for newly-diagnosed IS is higher than that of IS patients whose drug-therapy failed.KD therapy may be the top priority for IS patients and part of those patients whose drug-therapy failed can still get seizure-free with KD diet.

BACKGROUND:It is unclear whether serial cel passage in vitro influences the differentiation of bone marrow mesenchymal stem cel s into neural stem cel s.
OBJECTIVE:To investigate the effect of cel passage on the differentiation of bone marrow mesenchymal stem cel s into neural stem cel s.
METHODS:Rat bone marrow mesenchymal stem cel s were isolated and cultured by the whole bone marrow adherence method. Bone marrow mesenchymal stem cel s at passages 3, 6, 9, 12 were incubated in serum-free medium. After culture for 7 and 14 days, cel biological characterization was observed and differenitaiton ability into neural stem cel s was observed by detecting Nestin expression in cel s using flow cytometry. Then, the cel s were further induced to differentiate and cel multipotential differentiation capacity was detected by measurement of nerve enolase and glial acidic protein expression.
RESULTS AND CONCLUSION:Under induction, bone marrow mesenchymal stem cel s at different passages were al differentiated into Nestin-positive neural stem cel s. However, there was a significant difference in differentiation proportion of cel s at different passages (P<0.05). Strongest differentiation ability was found in the passage 6 cel s, with the Nestin expression up to (93.7±2.3)%at 7 days of induction and (96.2±1.8)%at 14 days of induction. The proportion of differentiated cel s at passages 6 and 9 was signfi cantly higher than that at passages 3 and 12. Moreover, adherent cel s were positive for nerve enolase and glial acidic protein. Al these findings indicate that the differentiation of bone marrow mesenchymal stem cel s into neural stem cel s is correlated with cel passage. Cel s at lower or higher passages are both detrimental to cel differentiation.