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.

OBJECTIVE To establish management index system for rational drug use of key monitoring drugs， and provide reference for the management of key monitoring drugs in the hospitals. METHODS First， the management index system for rational drug use of key monitoring drugs was drafted by collecting the evidence from related medical literature. Next， using a modified Delphi method， twenty experienced experts from the fields of pharmacy， medical practice， healthcare insurance， and finance were selected to participate in two rounds of questionnaire consultations. Based on the expert enthusiasm coefficient， authority coefficient， degree of opinion concentration， and degree of coordination， the final indicators were determined to establish a management index system for rational drug use of key monitored drugs in medical institutions. RESULTS The expert enthusiasm coefficients reached 100% in both rounds of consultation. In first-level， second-level and third-level indicators， the authority coefficients of experts were 0.89， 0.86 and 0.87， and coordination coefficients of the experts in importance score were 0.300 （P＜ 0.05）， 0.125 （P＜0.05） and 0.139 （P＜0.05）， respectively. The average score for the importance of all indicators reached over 3.5， in which the full score ratio ranged from 35% to 100%. Except that the variation coefficient of a third-level indicator “number of specifications purchased for key monitored drugs” was 0.26， the variation coefficients of rest indicators were less than or equal to 0.25. Based on the results of expert consultation， final version of the management index system established in this study， including two first-level indicators （drug procurement and use， and rational drug use）， five second-level indicators （such as the accessibility， cost-effectiveness） and twenty third-level indicators （such as the number of specifications purchased for key monitored drugs， the increase in the cost of key monitored drugs）. CONCLUSIONS The management index system established in this study possesses high reliability and strong operability， and may provide a reference for the management of key monitoring drugs in the hospitals.

The theory of"spleen and stomach deficiency and excess transformation"originates from Huangdi Neijing,which is based on the five elements theory.It systematically elucidates the physiological interconnections and pathological transmission relationships among spleen,stomach,and the five zang and six fu viscera.This theory was continuously developed and refined by later physicians.It was first systematically summarized and deepened by LI Dongyuan in his work Piwei Lun,which elaborates on the pathological transmission relationships of other zang-fu viscera after spleen and stomach deficiency.From the perspective of LI Dongyuan's theory of"spleen and stomach deficiency and excess transformation",this paper discusses the pathological relationships between spleen-earth,lung-metal,and kidney-water,and proposes that spleen-earth deficiency is the pathological basis for the onset of allergic rhinitis.Based on the pathological evolution following spleen-earth deficiency,the traditional Chinese medicine syndromes of allergic rhinitis were categorized into three types:earth deficiency with metal weakness,earth dryness with metal desiccation,and water cold with metal excess and earth decline.The treatment of allergic rhinitis should prioritize the spleen-earth,employing acrid and dispersing herbs with light properties to elevate the spleen,sweet-warm and sour-astringent herbs to tonify the spleen,and diuretic and dampness-resolving herbs to activate the spleen,thereby restoring spleen-earth function.Simultaneously,treatment should regulate lung-metal and kidney-water according to different pathological evolutions,incorporating cold-cool or acrid-warm herbs as appropriate,combining cold and warm properties,and treating both the manifestation and root cause of the disease.

Objective To investigate the common diseases and the causes of diseases in Chinese Antarctic researchers,so as to provide reference for the medical support.Methods Medical records of 1 127 people with injuries and diseases who participated in four Antarctic scientific expeditions(the 31st,35th,36th,and 39th time)were retrospectively analyzed.The causes of the injuries and diseases as well as the implications for nursing were investigated.Results The top 10 diseases in the four Antarctic expeditions were acute soft tissue injury,dermatomycosis,pharyngitis,insomnia,periodontitis,gastroenteritis,motion sickness,acute upper respiratory infection,primary hypertension,and frostbite.The causes of the diseases in the four Antarctic expeditions were analyzed,and the nursing of different diseases was proposed.Conclusion It is necessary to take preventive measures based on the characteristics of injuries and diseases during Antarctic expeditions,so as to effectively prevent and treat these diseases and provide more comprehensive medical support for Antarctic scientific expeditions.

Objective:To investigate the interaction between non-alcoholic fatty liver disease (NAFLD) and overweight/obesity on the risk of mild cognitive impairment (MCI) in elderly individuals.Methods:This cross-sectional study was based on the Hubei Memory and Aging Cohort Study (HMACS). Cluster random sampling was used to select 5 661 elderly individuals aged≥65 years in Wuhan from 2018 to 2023. Standardized neuropsychological assessments and clinical examinations results were collected. The NAFLD was diagnosed by abdominal ultrasound. The logistic regression analysis was used to analyze the association of NAFLD and overweight/obesity with MCI. The impacts of interaction between NAFLD and overweight/obesity on the risk of MCI were analyzed using both multiplicative and additive models.Results:Among the 5 661 elderly individuals included in the analysis, 2 563 were male and 3 098 were female, with a mean age of (72.24±5.51) years. A total of 2 239 participants (39.6%) resided in rural areas, 2 841 (50.2%) were overweight/obesity, 2 390 (42.2%) had NAFLD, and 1 694 (29.9%) were diagnosed with MCI. The risk of MCI in elderly individuals with NAFLD and overweight/obesity was 2.975 times ( OR=2.975, 95% CI: 2.489-3.557, P<0.001) of that in non-overweight/obese individuals without NAFLD. There was a multiplicative interaction between NAFLD and overweight/obesity on MCI ( OR=1.508, 95% CI: 1.169-1.944, P=0.002). NAFLD and overweight/obesity had an additive interaction effect on the risk of MCI, and the relative excess risk of interaction, attributable proportion of interaction and the synergy index was 1.099 (95% CI: 0.630-1.593), 0.369 (95% CI: 0.222-0.487), 2.256 (95% CI: 1.457-3.492), respectively. Conclusion:There is an interaction between NAFLD and overweight/obesity in elderly individuals, and the co-existence of NAFLD and overweight/obesity increases the risk of MCI in this population.

Objective:To develop an artificial intelligence (AI)-based platelet review strategy to identify abnormal platelet histograms with no significant difference between initial impedance platelet count (PLT-I) and PLT-F results.Methods:This study included 5 119 routine blood analysis in Nanfang Hospital of Southern Medical University and its Ganzhou branch from July 2023 and March 2024. Specimens exhibiting abnormal platelet histograms and an initial platelet count >40×10?/L underwent review using the fluorescent platelet count (PLT-F) channel. Consistency of the results was defined as a difference between impedance platelet count (PLT-I) and PLT-F less than ±20% of the PLT-F results. A deep learning model was developed using platelet and red blood cell histogram data from a training set of 3 807 specimens. The model′s diagnostic performance was evaluated on an independent external validation set ( n=805) using receiver operating characteristic (ROC) curve analysis. Changes in the number of reviewed samples and sample turnaround time were analyzed to assess its clinical utility. Results:The deep learning model based on platelet and red blood cell histograms achieved an area under the ROC curve (AUC) of 0.854 in the training set. At a cutoff value of 0.1, the sensitivity was 0.954 and specificity was 0.358. The model could reduce review by 16.80% (190/1 131). In the validation set, the AUC was 0.805, with a sensitivity of 0.955 and specificity of 0.307, corresponding to a reduction of 17.41% (47/270) in reviewed specimens.Conclusion:The platelet review prediction model developed based on deep learning technology can efficiently identify samples with consistent results before and after review, reducing unnecessary reviews and shortening specimen testing time, thereby improving the efficiency of platelet test.

The theory of"spleen and stomach deficiency and excess transformation"originates from Huangdi Neijing,which is based on the five elements theory.It systematically elucidates the physiological interconnections and pathological transmission relationships among spleen,stomach,and the five zang and six fu viscera.This theory was continuously developed and refined by later physicians.It was first systematically summarized and deepened by LI Dongyuan in his work Piwei Lun,which elaborates on the pathological transmission relationships of other zang-fu viscera after spleen and stomach deficiency.From the perspective of LI Dongyuan's theory of"spleen and stomach deficiency and excess transformation",this paper discusses the pathological relationships between spleen-earth,lung-metal,and kidney-water,and proposes that spleen-earth deficiency is the pathological basis for the onset of allergic rhinitis.Based on the pathological evolution following spleen-earth deficiency,the traditional Chinese medicine syndromes of allergic rhinitis were categorized into three types:earth deficiency with metal weakness,earth dryness with metal desiccation,and water cold with metal excess and earth decline.The treatment of allergic rhinitis should prioritize the spleen-earth,employing acrid and dispersing herbs with light properties to elevate the spleen,sweet-warm and sour-astringent herbs to tonify the spleen,and diuretic and dampness-resolving herbs to activate the spleen,thereby restoring spleen-earth function.Simultaneously,treatment should regulate lung-metal and kidney-water according to different pathological evolutions,incorporating cold-cool or acrid-warm herbs as appropriate,combining cold and warm properties,and treating both the manifestation and root cause of the disease.

Objective:To investigate the interaction between non-alcoholic fatty liver disease (NAFLD) and overweight/obesity on the risk of mild cognitive impairment (MCI) in elderly individuals.Methods:This cross-sectional study was based on the Hubei Memory and Aging Cohort Study (HMACS). Cluster random sampling was used to select 5 661 elderly individuals aged≥65 years in Wuhan from 2018 to 2023. Standardized neuropsychological assessments and clinical examinations results were collected. The NAFLD was diagnosed by abdominal ultrasound. The logistic regression analysis was used to analyze the association of NAFLD and overweight/obesity with MCI. The impacts of interaction between NAFLD and overweight/obesity on the risk of MCI were analyzed using both multiplicative and additive models.Results:Among the 5 661 elderly individuals included in the analysis, 2 563 were male and 3 098 were female, with a mean age of (72.24±5.51) years. A total of 2 239 participants (39.6%) resided in rural areas, 2 841 (50.2%) were overweight/obesity, 2 390 (42.2%) had NAFLD, and 1 694 (29.9%) were diagnosed with MCI. The risk of MCI in elderly individuals with NAFLD and overweight/obesity was 2.975 times ( OR=2.975, 95% CI: 2.489-3.557, P<0.001) of that in non-overweight/obese individuals without NAFLD. There was a multiplicative interaction between NAFLD and overweight/obesity on MCI ( OR=1.508, 95% CI: 1.169-1.944, P=0.002). NAFLD and overweight/obesity had an additive interaction effect on the risk of MCI, and the relative excess risk of interaction, attributable proportion of interaction and the synergy index was 1.099 (95% CI: 0.630-1.593), 0.369 (95% CI: 0.222-0.487), 2.256 (95% CI: 1.457-3.492), respectively. Conclusion:There is an interaction between NAFLD and overweight/obesity in elderly individuals, and the co-existence of NAFLD and overweight/obesity increases the risk of MCI in this population.

Objective:To develop an artificial intelligence (AI)-based platelet review strategy to identify abnormal platelet histograms with no significant difference between initial impedance platelet count (PLT-I) and PLT-F results.Methods:This study included 5 119 routine blood analysis in Nanfang Hospital of Southern Medical University and its Ganzhou branch from July 2023 and March 2024. Specimens exhibiting abnormal platelet histograms and an initial platelet count >40×10?/L underwent review using the fluorescent platelet count (PLT-F) channel. Consistency of the results was defined as a difference between impedance platelet count (PLT-I) and PLT-F less than ±20% of the PLT-F results. A deep learning model was developed using platelet and red blood cell histogram data from a training set of 3 807 specimens. The model′s diagnostic performance was evaluated on an independent external validation set ( n=805) using receiver operating characteristic (ROC) curve analysis. Changes in the number of reviewed samples and sample turnaround time were analyzed to assess its clinical utility. Results:The deep learning model based on platelet and red blood cell histograms achieved an area under the ROC curve (AUC) of 0.854 in the training set. At a cutoff value of 0.1, the sensitivity was 0.954 and specificity was 0.358. The model could reduce review by 16.80% (190/1 131). In the validation set, the AUC was 0.805, with a sensitivity of 0.955 and specificity of 0.307, corresponding to a reduction of 17.41% (47/270) in reviewed specimens.Conclusion:The platelet review prediction model developed based on deep learning technology can efficiently identify samples with consistent results before and after review, reducing unnecessary reviews and shortening specimen testing time, thereby improving the efficiency of platelet test.

Objective To explore the expression and diagnostic value of circulating microRNA(miR)-126-3p in non-small cell lung cancer(NSCLC).Methods Multi-centred miR chips and sequencing data were col-lected to investigate the differential expression of circulating miR-126-3p in NSCLC.In order to evaluate the comprehensive expression level of circulating miR-126-3p in the cycle,the standardized mean difference(SMD)and summary receiver operating characteristic(sROC)curve were calculated,and the area under curve(AUC)of sROC curve was analyzed.Sensitivity,specificity,positive negative likelihood ratio were ex-plored,and the expression of circulating miR-126-3p was further comprehensively analyzed in combination with tissue.By using miRDB,starBase v2.0,and TargetScan 7.1,combined with up-regulated differentially expressed genes in NSCLC,potential target genes of circulating miR-126-3p were screened using complemen-tary sequence method.Results Based on six circulating miR datasets,the expression level of circulating miR-126-3p was higher than that of the control group,and the difference was statistically significant(P＜0.05).The receiver operating characteristic curves showed that circulating miR-126-3p had strong diagnostic efficacy(AUC＞0.5),and the comprehensive expression of circulating miR-126-3p was lower in 199 cases of NSCLC group than in the control group(SMD=-1.46).The sROC curve showed that circulating miR-126-3p distin-guished the NSCLC group from the control group with high accuracy(AUC=0.91),Egger's test showed no publication bias(P＞0.05),with sensitivity and specificity 0.80,and positive likelihood ratio and negative likelihood ratio were 5.37 and 0.18,respectively.In addition,a comprehensive analysis of the circulation and tissue of 1 320 NSCLC samples from 26 datasets showed that circulating miR-126-3p expression was lower in NSCLC group than in the control group(SMD=-2.07).The sROC curve showed that low-expression circu-lating miR-126-3p had high accuracy in distinguishing between the NSCLC group and the control group(AUC=0.97).In addition,potential target genes ADAM9 and SLC7A5 were screened for circulating miR-126-3p,and their expression in NSCLC group was higher than that in the control group.Conclusion Low ex-pression of circulating miR-126-3p in the circulation may be an important biomarker for high-precision screen-ing of NSCLC.