Adverse drug reactions (ADRs) significantly impact clinical medication safety. The timely identification and prediction of ADRs rely on the efficient analysis of real-world data, such as electronic health records, social media, and spontaneous reporting databases. In recent years, the rapid advancement of artificial intelligence, particularly large language models, in natural language processing, causal reasoning, and complex data mining has provided new technological means for real-time ADRs monitoring and individualized prediction. This paper summarizes the latest research achievements in AI-driven ADRs monitoring. Focusing on diverse data sources, including structured databases and electronic health records, it elaborates on the advantages andchallenges of AI in ADRs event extraction, relationship identification, causal analysis, and risk prediction. The aim is to provide a theoretical reference for constructing more intelligent and efficient ADRs monitoring systems.

INTRODUCTION: The diagnosis of sarcopenia relies on key indicators such as handgrip strength, walking speed and muscle mass. Developing a composite index that integrates these measures could enhance clinical evaluation in older adults. This study aimed to standardise and combine these metrics to establish a z score for the sarcopenia composite index (ZoSCI) tailored for the ageing population. Additionally, we explore the risk factors associated with ZoSCI to provide insights into early prevention and intervention strategies. METHOD: This retrospective study analysed data between January 2017 and December 2021 from an elderly health programme in Taiwan, applying the Asian Working Group for Sarcopenia criteria to assess sarcopenia. ZoSCI was developed by standardising handgrip strength, walking speed and muscle mass into z scores and integrating them into a composite index. Receiver operating characteristic (ROC) curve analysis was used to determine optimal cut-off values, and multiple regression analysis identified factors influencing ZoSCI. RESULTS: Among the 5047 participants, the prevalence of sarcopenia was 3.7%, lower than the reported global prevalence of 3.9-15.4%. ROC curve analysis established optimal cut-off points for distinguishing sarcopenia in ZoSCI: -1.85 (sensitivity 0.91, specificity 0.88) for males and -1.97 (sensitivity 0.93, specificity 0.88) for females. Factors associated with lower ZoSCI included advanced age, lower education levels, reduced exercise frequency, lower body mass index and creatinine levels. CONCLUSION This study introduces ZoSCI, a new compo-site quantitative indicator for identifying sarcopenia in older adults. The findings highlight specific risk factors that can inform early intervention. Future studies should validate ZoSCI globally, with international collaborations to ensure broader applicability.
Humans ; Sarcopenia/physiopathology* ; Male ; Aged ; Female ; Retrospective Studies ; Hand Strength ; Taiwan/epidemiology* ; ROC Curve ; Aged, 80 and over ; Risk Factors ; Walking Speed ; Geriatric Assessment/methods* ; Prevalence ; Muscle, Skeletal ; Middle Aged

Objective:To evaluate the role of ryanodine receptor 2 (RyR2) in postoperative cognitive dysfunction (POCD) in aged rats.Methods:Sixty SPF healthy male Sprague-Dawley rats, aged 20 months, weighing 600-650 g, were divided into 3 groups ( n=20 each) using a random number table method: control group (group C), POCD group (group P) and dantrolene group (group D). A rat POCD model was prepared by closed reduction and internal fixation of left tibial fractures with sevoflurane anesthesia in P and D groups. RyR inhibitor dantrolene 2 mg/kg was injected via a tail vein at 30 min before surgery in group D. Morris water maze tests were conducted on day 1 before surgery and day 7 after surgery to evaluate the cognitive function. An open field test was conducted to detect the spontaneous motor function starting from day 7 after surgery. The rats were sacrificed after the end of Morris water maze tests and hippocampal tissues were taken for determination of the expression of RyR2 and cleaved caspase-3 (by Western blot), apoptosis rate and cytoplasmic calcium ion concentrations (by flow cytometry) and for microscopic examination of the pathological changes in hippocampal CA1 area (using HE staining). Results:There was no significant difference in the speed, distance and duration of stay in the center in the open field test among the three groups ( P>0.05). Compared with group C, the escape latency was significantly prolonged after surgery, the number of crossing the original platform was reduced, the expression of RyR2 and cleaved caspase-3 was up-regulated, and the neuronal apoptosis rate and cytoplasmic calcium ion concentration were increased ( P<0.05), and the pathological changes were found in the hippocampal CA1 area in group P. Compared with group P, the escape latency was significantly shortened after surgery, the number of crossing the original platform was increased, the expression of RyR2 and cleaved caspase-3 was down-regulated, and the neuronal apoptosis rate and cytoplasmic calcium ion concentration were decreased ( P<0.05), and the pathological changes were significantly reduced in the hippocampal CA1 area in group D. Conclusions:RyR2 activation is involved in the process of POCD in aged rats, which may be associated with increased calcium overload-induced hippocampal neuronal apoptosis.

Objective:To evaluate the effect of intermittent fasting on postoperative cognitive function in aged rats and the role of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in it.Methods:Eighty SPF healthy male Sprague-Dawley rats, aged 20 months, weighing 600-650 g, were divided into 4 groups ( n=20 each) using a random number table method: control group (group C), postoperative cognitive dysfuction (POCD) group (group P), intermittent fasting + POCD group (group IF+ P), and intermittent fasting+ JAK2/STAT3 signaling pathway agonist C-A1+ POCD group (group IF+ A+ P). IF+ P group and IF+ A+ P group underwent a 4-week intermittent fasting procedure: fasting for 24 h followed by free eating for 24 h, without limiting water intake throughout the entire process, in addition C-A1 100 μg/kg was intraperitoneally injected daily during intermittent fasting in IF+ A+ P group. Rats underwent exploratory laparotomy under sevoflurane anesthesia to prepare POCD models in P group, IF+ P group and IF+ A+ P group. Three days after surgery, open field tests were conducted to evaluate the autonomous motor function of rats, and Morris water maze tests were conducted to evaluate the cognitive function of rats on 3-7 days after surgery. After the Morris water maze tests, the rats were sacrificed and the hippocampal CA1 area was removed for determination of the expression of JAK2, phosphorylated JAK2 (p-JAK2), STAT3, and phosphorylated STAT3 (p-STAT3) (by Western blot) and contents of interleukin-6 (IL-6), IL-1β and tumor necrosis factor-alpha (TNF-α) (by enzyme-linked immunosorbent assay) and for microscopic examination of pathological changes of hippocampal CA1 region (using HE staining). Results:There was no statistically significant difference in the speed, distance and duration of stay at the center of the open field test among the four groups ( P>0.05). Compared with group C, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, and the p-JAK2/JAK2 ratio, p-STAT3/STAT3 ratio and contents of IL-6, IL-1β and TNF-α in the hippocampal CA1 region were increased ( P<0.05), and the pathological damage occurred in the hippocampal CA1 region in group P. Compared with P group, the escape latency was significantly shortened, the number of crossing the original platform was increased, and the p-JAK2/JAK2 ratio, p-STAT3/STAT3 ratio and contents of IL-6, IL-1β and TNF-α in the hippocampal CA1 region were decreased ( P<0.05), and the pathological damage in the hippocampal CA1 area was significantly alleviated in IF+ P group. Compared with IF+ P group, the escape latency was significantly prolonged, the number of crossing the original platform was reduced, and the p-JAK2/JAK2 ratio, p-STAT3/STAT3 ratio and contents of IL-6, IL-1β and TNF-α in the hippocampal CA1 region were increased ( P<0.05), and the pathological damage in the hippocampal CA1 area was aggravated in group IF+ A+ P. Conclusions:Intermittent fasting can improve postoperative cognitive function in aged rats, and the mechanism may be related to inhibiting the JAK2/STAT3 signaling pathway and reducing the neuroinflammatory responses in the hippocampal CA1 region.

Objective To evaluate the molecular mechanisms by which dendritic cells(DCs)detect variations in the extracellular mechanical microenvironment and dynamically adjust their migration behavior.Methods Hydrogel substrates with varied stiffness were constructed to investigate the influence of the mechanical microenvironment on the DC migration behavior.A fibrotic rat liver model was established in combination with immunohistochemistry experiments to investigate the effect of liver fibrosis on the DC migration capability.Furthermore,potential key molecules involved in the mechanical sensing cascade during DC migration were analyzed using single-cell sequencing data from human/mouse fibrotic livers.Moreover,RT-qPCR was used to examine the expression levels of these key molecules in mouse DCs on substrates of different stiffness.Results The migration capability of DCs on stiff substrates was significantly lower than that on soft substrates.The DC infiltration in fibrotic rat livers increased,and 682 differentially expressed genes(DEGs)were observed between liver-infiltrating DCs from cirrhosis patients and normal individuals.Furthermore,focusing on genes relevant to cytoskeleton regulation and migration based on KEGG and GO pathway enrichment analysis,12 potential key molecules mediating stiffness detection during DC migration were identified.Among these,the expression levels of AIF1,GPR65,MYL12B,RAC1,and RHOG were upregulated in patients with liver cirrhosis,whereas those of ACTB,ACTG1,ARF6,CDC42,COTL1,PFN1,and TMSB10 were downregulated.Subsequently,the expression levels of ACTB and CDC42 were downregulated in mouse DCs grown on stiff substrates.This was consistent with the circumstance of liver-infiltrating DC in human cirrhotic patients.Conclusions Liver fibrosis potentially impairs DC migration and thereby,results in increased DC infiltration.ACTB and CDC42 are potential regulators of DC stiffness during migration.This study has provided a theoretical basis and an inspiring novel strategy for optimizing DC-mediated antitumor immune functions.

Objective To evaluate the molecular mechanisms by which dendritic cells(DCs)detect variations in the extracellular mechanical microenvironment and dynamically adjust their migration behavior.Methods Hydrogel substrates with varied stiffness were constructed to investigate the influence of the mechanical microenvironment on the DC migration behavior.A fibrotic rat liver model was established in combination with immunohistochemistry experiments to investigate the effect of liver fibrosis on the DC migration capability.Furthermore,potential key molecules involved in the mechanical sensing cascade during DC migration were analyzed using single-cell sequencing data from human/mouse fibrotic livers.Moreover,RT-qPCR was used to examine the expression levels of these key molecules in mouse DCs on substrates of different stiffness.Results The migration capability of DCs on stiff substrates was significantly lower than that on soft substrates.The DC infiltration in fibrotic rat livers increased,and 682 differentially expressed genes(DEGs)were observed between liver-infiltrating DCs from cirrhosis patients and normal individuals.Furthermore,focusing on genes relevant to cytoskeleton regulation and migration based on KEGG and GO pathway enrichment analysis,12 potential key molecules mediating stiffness detection during DC migration were identified.Among these,the expression levels of AIF1,GPR65,MYL12B,RAC1,and RHOG were upregulated in patients with liver cirrhosis,whereas those of ACTB,ACTG1,ARF6,CDC42,COTL1,PFN1,and TMSB10 were downregulated.Subsequently,the expression levels of ACTB and CDC42 were downregulated in mouse DCs grown on stiff substrates.This was consistent with the circumstance of liver-infiltrating DC in human cirrhotic patients.Conclusions Liver fibrosis potentially impairs DC migration and thereby,results in increased DC infiltration.ACTB and CDC42 are potential regulators of DC stiffness during migration.This study has provided a theoretical basis and an inspiring novel strategy for optimizing DC-mediated antitumor immune functions.

Good sleep is essential for children′s physical and mental health, growth, and development.Adequate and high-quality sleep positively impacts children′s quality of life, memory, learning, attention, mood, and behavior.Children of different ages have different sleep needs.Children have various sleep problems in different cultures.Therefore, it is significant to guide children to get healthy sleep by popularizing the sleep problems of Chinese children of all ages and in all dimensions.Based on China′s social and cultural background, this paper summarizes the contents related to children′s sleep physiology, good sleep habits, common sleep problems, sleep apnea disorders, hypnagogic sleep, narcolepsy, insomnia, and other issues that interfere with children′s sleep.Chinese sleep experts summarize and interpret the 100 sleep health problems of children that medical workers and parents are most concerned about.To promote children′s sleep health and popularize solutions to sleep problems.

Objective:To explore the effects of acute sleep fragmentation (SF) on cognitive function and the relationship between hippocampal Homer1a and synaptic plasticity in aged rats.Methods:One hundred and eight SPF grade male SD rats aged 22 to 24 months were divided into three groups according to random number table: control group (Control group), non-sleep fragmentation group (NSF group) and sleep fragmentation group (SF group), with 36 rats in each group.A sleep fragmentation model was established by sleep deprivation rod method.Morris water maze and novel object recognition tests were used to evaluate the learning and memory function of rats.Homer1a expression in hippocampus was detected by Western blot, and its distribution in CA1 area of hippocampus was observed by immunohistochemical staining.Golgi staining was used to observe the density of dendritic spines in CA1 area of hippocampus, and in vitro electrophysiological patch clamp test was used to detect the slope of field excitatory postsynaptic potential(fEPSP) from CA3 to CA1 in hippocampus.SPSS 22.0 and GraphPad Prism 9.3 softwares were used for data statistical analysis and mapping.One-way ANOVA was used for comparison among groups, and Tukey-Kramer test was used for further pairwise comparison. Results:(1)In the behavioral tests, there were statistical differences in the times of crossing the original platform, the target quadrant residence time and the new object recognition index at 1 h and 24 h among the three groups( F=13.63, 11.34, 21.26, 16.22, all P<0.01). The times of crossing the original platform in SF group((2.00±1.27) times) was lower than that of Control group ((5.67±2.16) times) and NSF group ((6.50±2.35) times) (both P<0.05). The target quadrant residence time in SF group ((9.02±4.84) s) was shorter than that in Control group ((24.73±7.37) s) and NSF group ((27.81±8.37)s) (both P<0.05). The new object recognition index at 1 h and 24 h in SF group were lower than those in Control group and NSF group (all P<0.05). (2) In Western blot assay, the expression of Homer1a protein in hippocampus of SF group(0.91±0.13) was higher than that of Control group(0.70±0.05) and NSF group(0.74±0.04)(both P<0.05). (3) In immunohistochemical staining, the optical density value of the Homer1a protein in CA1 area of hippocampus in the SF group was higher than that in the Control group and NSF group(both P<0.05). (4) In Golgi staining, the density of dendritic spines in CA1 area of hippocampus in SF group was lower than that in Control group and NSF group (both P<0.05). (5) In vitro electrophysiological test showed that the slope of fEPSP in CA3-CA1 area of hippocampus in SF group were lower than that in Control group and NSF group (both P<0.05). Conclusion:Acute SF intervention in aged rats can cause cognitive impairment, which may be associated with the inhibition of hippocampal synaptic plasticity induced by hippocampal Homer1a overexpression.

Objective:To evaluate the relationship between Karyopherin β2 (Kapβ2)-mediated nuclear translocation of nuclear inhomogeneous ribonucleoprotein A2/B1 (hnRNPA2/B1) and sevoflurane-induced brain neurotoxicity in a cellular experiment.Methods:The mouse hippocampal neuronal cell line HT22 cells were inoculated in confocal culture dishes and 6-well culture plates at a density of 2×10 5 cells/well and 1×10 6 cells/well and divided into 4 groups( n=12 each) by a random number table method: control group (GFP-C group) carrying green fluorescent protein (GFP) with empty adenovirus transfection, sevoflurane group (GFP-Sev group) carrying GFP with empty adenovirus transfection, control group (GFP-Sev group) transfected with Kapβ2 gene-overexpressing adenovirus, and sevoflurane group (Kapβ2-Sev group) transfected with Kapβ2 gene-overexpressing adenovirus. After 48 h of conventional incubation, empty adenovirus-carrying GFP (GFP-C and GFP-Sev groups) and Kapβ2 gene-overexpressing adenovirus (Kapβ2-C and Kapβ2-Sev groups) were transfected. After 48 h of transfection, the cells were conventionally incubated continuously in GFP-C and Kapβ2-C groups, and the cells were incubated for 3 h with 3% sevoflurane and then were conventionally incubated for 48 h in GFP-Sev and Kapβ2-Sev groups. The expression of Kapβ2, synaptophysin (SYP), postsynaptic density protein 95 (PSD95) and hnRNPA2/B1 nucleoplasmic ratio were measured in cells by Western blot. Immunofluorescence assay was used for hnRNPA2/B1 subcellular localization. Results:Compared with GFP-C group, the expression of SYP and PSD95 was significantly down-regulated, hnRNPA2/B1 nucleoplasmic ratio was decreased, and cytoplasmic hnRNPA2/B1 expression was up-regulated in GFP-Sev group, and Kapβ2 expression was significantly up-regulated in Kapβ2-C group ( P<0.05). Compared with Kapβ2-C group, the expression of SYP and PSD95 was significantly down-regulated, hnRNPA2/B1 nucleoplasmic ratio was decreased, and cytoplasmic hnRNPA2/B1 expression was up-regulated in Kapβ2-Sev group ( P<0.05). Compared with GFP-Sev group, the expression of Kapβ2, SYP and PSD95 was significantly up-regulated, hnRNPA2/B1 nucleoplasmic ratio was increased, and cytoplasmic hnRNPA2/B1 expression was down-regulated in Kapβ2-Sev group ( P<0.05). Conclusions:Kapβ2-mediated hnRNPA2/B1 nuclear translocation may be the endogenous protective mechanism against sevoflurane-induced brain neurotoxicity.

Objective:To identify the risk factors for postoperative cognitive dysfunction (POCD) and develop the prediction model in elderly patients undergoing lumbar surgery under general anesthesia.Methods:The elderly patients undergoing elective lumbar surgery under general anesthesia in our hospital from July 2021 to July 2022 were enrolled. Cognitive function was assessed at 7 days after surgery using Mini-Mental State Examination and Montreal Cognitive Assessment. When the decrease in both scales≥ 1 standard deviation, the patients were considered as having POCD. The patients were divided into POCD group and non-POCD group according to whether POCD developed. The propensity score matching was used to balance the confounding bias between two groups. The multivariate logistic regression analysis was used to identify the risk factors for POCD. The prediction model was constructed, and a nomogram was drawn for visualization of the model. The receiver operating characteristic curve, calibration plot and decision curve analysis (DCA) were drawn to evaluate the differentiation, consistency and clinical validity of the model, respectively.Results:A total of 159 patients were enrolled in this study, and the incidence of POCD was 31.4%. There were statistically significant differences in the ratio of intraoperative blood transfusion, cumulative time of hypotension, total infusion volume and operation time between two groups ( n=32 each) after propensity score matching ( P<0.05). The results of multivariate logistic regression showed that age, educational levels, diabetes mellitus, previous two or more operations under general anesthesia, APTT and cumulative time of hypotension were independent risk factors for POCD in elderly patients undergoing lumbar surgery under general anesthesia ( P<0.05). A model was developed based on the risk factors mentioned above: LogitP=-15.878+ 0.263 × Age (years) - 0.122 × Educational Level (years)+ 1.601 × Diabetes Mellitus+ 1.468 × History of General Anesthesia for 2 or more times+ 0.608 × Cumulative Time of Hypotension(min) - 0.140 × APTT (s). The area under the receiver operating characteristic curve was 0.930 (95% CI 0.887-0.973), the sensitivity was 0.920, specificity was 0.798 and Youden index was 0.718. After visualizing the model via nomogram, the model was verified by Hosmer-Lemeshow test, P=0.403, C index was 0.930, and corrected C index was 0.914. Conclusions:Age, educational levels, diabetes mellitus, previous multiple operations under general anesthesia, APTT and cumulative time of hypotension are independent risk factors for POCD in elderly patients undergoing lumbar surgery under general anesthesia, and the established risk prediction model can effectively predict the occurrence of POCD in elderly patients undergoing lumbar surgery under general anesthesia.