The c-Jun N-terminal kinase （JNK） signaling pathway， a key member of the mitogen-activated protein kinase （MAPK） family， plays a central role in the pathogenesis and progression of central nervous system （CNS） diseases by regulating core biological processes such as apoptosis， inflammatory responses， synaptic plasticity， and autophagy. This article sorts out and analyzes relevant literature published domestically and internationally in recent years， summarizing the mechanisms of action of the JNK signaling pathway in common CNS diseases and the research progress in traditional Chinese medicine （TCM） interventions in CNS diseases through the regulation of the JNK signaling pathway. Studies have shown that active components of TCM， such as berberine， paeoniflorin， and astragaloside Ⅳ， as well as compound formulations like Heixiaoyao san， Ditan tang， and Buyang huanwu tang， can exert neuroprotective effects in various CNS disorders， including Alzheimer’s disease， Parkinson’s disease， cerebral ischemia-reperfusion injury， and epilepsy， by inhibiting the aberrant activation of the JNK signaling pathway， thereby alleviating neuroinflammation， oxidative stress， and neuronal apoptosis， while improving synaptic function and cognitive behavioral deficits， regulating autophagy， and maintaining blood-brain barrier integrity.

Alzheimer’s disease （AD） is an age-related neurodegenerative disorder. Marrow-sea insufficiency serves as the fundamental basis for the onset of AD. Early syndrome differentiation-based intervention helps to delay disease progression， and improve patients’ cognitive function. Qifu yin is a representative specialized prescription for AD with marrow-sea insufficiency syndrome. Studies demonstrate that Qifu yin exerts neuroprotective effects through multiple pathways， including inhibiting the abnormal deposition of amyloid β -protein and hyperphosphorylation of tau protein， alleviating neuroinflammation， regulating oxidative stress and mitochondrial dysfunction， modulating the cholinergic system， and improving synaptic plasticity. Qifu yin combined with Western medicine such as donepezil， memantine， and butylphthalide， or combined with external therapies such as acupuncture， can effectively improve cognitive function and activities of daily living in AD patients with favorable safety. Future research should focus on the core pathogenesis and key targets of AD with marrow-sea insufficiency syndrome， provide in-depth elucidation of the scientific connotation of Qifu yin’s “tonifying the kidney to produce marrow”， and further conduct high-quality clinical studies to provide scientific evidence for the prevention and treatment of AD with marrow-sea insufficiency syndrome.

ObjectiveTo observe the effects of Qingxin Jieyu granules （QXJYG） on FeCl₃-induced carotid artery thrombosis in rats and on the expression of thrombosis-related proteins tissue factor （TF） and tissue factor pathway inhibitor （TFPI） as well as the protein kinase B （Akt）/nuclear factor-κB （NF-κB） signaling pathway in EA.hy926 cells exposed to tumor necrosis factor-α （TNF-α）， thus preliminarily exploring the mechanism of QXJYG in inhibiting thrombosis. MethodsThirty-six SD rats were randomized into normal control， model， positive control （aspirin， 9 mg·kg^-1）， and low-， medium-， and high-dose （0.99， 1.98， 3.96 g·kg^-1， respectively） QXJYG groups （n=6）. The rats in the drug treatment groups were administrated with corresponding drugs， and those in the normal control group and model group were given an equal volume of distilled water. After 14 consecutive days of prophylactic gavage， the rat model of common carotid artery thrombosis was established with 45% FeCl₃ solution， and the blood vessels were collected and the wet weight of thrombus was weighed by an electronic balance （precision of 1/10 000）. The thrombosis in the common carotid artery of each group of rats was observed by hematoxylin-eosin staining. The plasma levels of von Willebrand factor （vWF）， platelet endothelial cell adhesion molecule-1 （PECAM-1）， tissue-type plasminogen activator （t-PA）， and plasminogen activator inhibitor-1 （PAI-1） were determined by enzyme-linked immunosorbent assay. An endothelial cell injury model was established by treating EA.hy926 human umbilical vein endothelial cells with TNF-α. The cell counting kit-8 method was used to screen the intervention concentrations of QXJYG. Western blot was employed to determine the protein levels of TF， TFPI， Akt， p-Akt， NF-κB p65， and p-NF-κB p65 in each group of cells. ResultsThe animal experiment showed that compared with the normal control group， the model group showed an increase in carotid artery thrombus weight （P<0.05）， with unclear vascular structure and extensive thrombosis in the lumen. In addition， the plasma levels of vWF， PECAM-1， and PAI-1 were elevated， while the t-PA level became lowered （P<0.05） in the model group. Compared with the model group， the aspirin and QXJYG groups showed reductions in the weight of FeCl₃-induced carotid artery thrombi （P<0.05） and thrombosis in the lumen， declines in plasma levels of PECAM-1 and PAI-1， and an elevation in the t-PA level （P<0.05）. Moreover， the QXJYG groups showed reductions in the plasma level of vWF （P<0.05）， which， however， had no significant difference between the aspirin group and the model group. The cell experiments indicated that 31.25， 62.5， 125， 250， 500 mg·L^-1 QXJYG had no effect on the viability of EA.hy926 cells. Therefore， 250， 500 mg·L^-1 QXJYG were selected as the intervention concentrations for subsequent experiments. Western blotting results showed that compared with the control group， the TNF-α stimulation downregulated the expression of TFPI （P<0.05）， upregulated the expression of TF， and increased the ratios of p-Akt/Akt and p-NF-κB p65/NF-κB p65 （P<0.05） in EA.hy926 cells. Compared with the model group， the intervention with QXJYG upregulated the expression of TFPI （P<0.05）， inhibited the expression of TF， and decreased the ratios of p-Akt/Akt and p-NF-κB p65/NF-κB p65 （P<0.05）. ConclusionQXJYG has the effect of inhibiting thrombosis and regulating the expression of TF and TFPI in endothelial cells exposed to TNF-α by suppressing the abnormal activation of the Akt/NF-κB signaling pathway.

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.

Objective To observe the effect of Qing-Xin-Jie-Yu granule(QXJYG)on the formation of thrombosis in the rat model of arteriovenous bypass thrombosis and the adenosine diphosphate(ADP)-induced platelet aggregation.Methods Thirty-six male SD rats were randomly divided into normal control group,model group,clopidogrel positive control group,QXJYG low-dose,medium-dose and high-dose groups,with 6 rats in each group.The dose of clopidogrel positive control group was 6.74 mg/(kg?d),the dosages of QXJYG in low,medium and high groups were 0.99,1.98,3.96 g/(kg?d),respectively,normal control group and model group were given equal volume of distilled water,and continuous prophylactic intragastric administration for 14 days,once a day.One hour after the final administration,the rats were anesthetized,and the arteriovenous bypass thrombosis model was established by using a polyethylene tube as the arteriovenous bypass bridge(except control group).The thrombus was extracted after 15 min and its weight was weighed by 1/10,000th precision electronic balance.The levels of thromboxane B2(TXB2)and 6-keto-prostaglandin F1α(6-keto-PGF1α)in plasma were determined by ELISA kits.The rate of platelet aggregation induced by ADP in each group was measured using a microplate reader by turbidimetric method.Results Compared with the control group,the weight of arteriovenous bypass thrombus was significantly higher,the level of TXB2 in plasma was significantly higher,while the level of 6-keto-PGF1α was significantly lower,and platelet aggregation was significantly higher after ADP induction in the model group(P＜0.05).Compared with the model group,the weight of arteriovenous bypass thrombosis in clopidogrel positive control group and QXJYG dose groups was significantly decreased(P＜0.05);the inhibition rate of thrombosis formation was 53.80％,23.96％,33.63％,and 32.59％,respectively.The content of TXB2 in plasma was significantly decreased,the content of 6-keto-PGF1α was significantly increased;additionally,the platelet aggregation rate induced by ADP was reduced in clopidogrel positive control group and QXJYG group.Meanwhile,there was a dose-dependence between different doses in QXJYY group(P＜0.05),and the inhibition rate of platelet aggregation was 86.90％,26.17％,38.87％,54.48％,respectively.Conclusion QXJYG can prevent thrombosis formation in the rat model of arteriovenous bypass thrombosis and inhibit platelet aggregation induced by ADP.

Objective:To explore the early predictive value of the triglyceride-glucose (TyG) index and the controlling nutritional status (CONUT) score for severe acute pancreatitis (SAP).Methods:Clinical data from 1 050 hospitalized patients with acute pancreatitis (AP) at the General Hospital of Central Theater Command between January 2019 and December 2023 were retrospectively analyzed. Patients were categorized into mild acute pancreatitis (MAP) group ( n=606), moderately severe acute pancreatitis (MSAP) group ( n=320), and SAP group ( n=124) based on AP severity. General clinical data, laboratory parameters, modified computed tomography severity index (MCTSI), bedside index for severity in acute pancreatitis (BISAP), TyG index, and CONUT score were compared among the three groups. Spearman correlation analysis was used to evaluate the relationship between TyG index, CONUT score and AP severity. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for AP severity. Receiver operating characteristic curves (ROC) were plotted to calculate the area under the curve (AUC), sensitivity, and specificity for evaluating the predictive efficacy of TyG index, CONUT score, and their combination for SAP. Results:Significant differences on TyG index and CONUT score were observed among AP patients with varying severity (all P value <0.001). Spearman correlation analysis further revealed positive correlations of TyG index ( r=0.174), CONUT score ( r=0.306) with AP severity (both P<0.001). Multivariate logistic regression identified neutrophil count ( OR=1.076, 95% CI 1.027-1.125), MCTSI ( OR=2.565, 95% CI 2.250-2.921), BISAP ( OR=3.522, 95% CI 2.726-4.549), TyG index ( OR=1.859, 95% CI 1.276-2.707), and CONUT score ( OR=1.155, 95% CI 1.035-1.288) as independent risk factors for AP severity. The combined predictive model equation was: -7.342+0.76×TyG+0.439×CONUT. ROC analysis showed that the AUC values of the TyG index, CONUT score, and the combined index (TyG index+CONUT score) were 0.583 (95% CI 0.529-0.637), 0.701 (95% CI 0.652-0.75), and 0.755 (95% CI 0.710-0.801), with sensitivities of 0.706, 0.677, and 0.742, and specificities of 0.884, 0.629, and 0.657, respectively (all P value <0.05). Conclusions:TyG index and CONUT score are positively correlated with AP severity and may serve as reliable predictors for SAP. Their combination could enhance the predictive accuracy for AP.

Objective:To explore the early predictive value of the triglyceride-glucose (TyG) index and the controlling nutritional status (CONUT) score for severe acute pancreatitis (SAP).Methods:Clinical data from 1 050 hospitalized patients with acute pancreatitis (AP) at the General Hospital of Central Theater Command between January 2019 and December 2023 were retrospectively analyzed. Patients were categorized into mild acute pancreatitis (MAP) group ( n=606), moderately severe acute pancreatitis (MSAP) group ( n=320), and SAP group ( n=124) based on AP severity. General clinical data, laboratory parameters, modified computed tomography severity index (MCTSI), bedside index for severity in acute pancreatitis (BISAP), TyG index, and CONUT score were compared among the three groups. Spearman correlation analysis was used to evaluate the relationship between TyG index, CONUT score and AP severity. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for AP severity. Receiver operating characteristic curves (ROC) were plotted to calculate the area under the curve (AUC), sensitivity, and specificity for evaluating the predictive efficacy of TyG index, CONUT score, and their combination for SAP. Results:Significant differences on TyG index and CONUT score were observed among AP patients with varying severity (all P value <0.001). Spearman correlation analysis further revealed positive correlations of TyG index ( r=0.174), CONUT score ( r=0.306) with AP severity (both P<0.001). Multivariate logistic regression identified neutrophil count ( OR=1.076, 95% CI 1.027-1.125), MCTSI ( OR=2.565, 95% CI 2.250-2.921), BISAP ( OR=3.522, 95% CI 2.726-4.549), TyG index ( OR=1.859, 95% CI 1.276-2.707), and CONUT score ( OR=1.155, 95% CI 1.035-1.288) as independent risk factors for AP severity. The combined predictive model equation was: -7.342+0.76×TyG+0.439×CONUT. ROC analysis showed that the AUC values of the TyG index, CONUT score, and the combined index (TyG index+CONUT score) were 0.583 (95% CI 0.529-0.637), 0.701 (95% CI 0.652-0.75), and 0.755 (95% CI 0.710-0.801), with sensitivities of 0.706, 0.677, and 0.742, and specificities of 0.884, 0.629, and 0.657, respectively (all P value <0.05). Conclusions:TyG index and CONUT score are positively correlated with AP severity and may serve as reliable predictors for SAP. Their combination could enhance the predictive accuracy for AP.

Objective To observe the effect of Qing-Xin-Jie-Yu granule(QXJYG)on the formation of thrombosis in the rat model of arteriovenous bypass thrombosis and the adenosine diphosphate(ADP)-induced platelet aggregation.Methods Thirty-six male SD rats were randomly divided into normal control group,model group,clopidogrel positive control group,QXJYG low-dose,medium-dose and high-dose groups,with 6 rats in each group.The dose of clopidogrel positive control group was 6.74 mg/(kg?d),the dosages of QXJYG in low,medium and high groups were 0.99,1.98,3.96 g/(kg?d),respectively,normal control group and model group were given equal volume of distilled water,and continuous prophylactic intragastric administration for 14 days,once a day.One hour after the final administration,the rats were anesthetized,and the arteriovenous bypass thrombosis model was established by using a polyethylene tube as the arteriovenous bypass bridge(except control group).The thrombus was extracted after 15 min and its weight was weighed by 1/10,000th precision electronic balance.The levels of thromboxane B2(TXB2)and 6-keto-prostaglandin F1α(6-keto-PGF1α)in plasma were determined by ELISA kits.The rate of platelet aggregation induced by ADP in each group was measured using a microplate reader by turbidimetric method.Results Compared with the control group,the weight of arteriovenous bypass thrombus was significantly higher,the level of TXB2 in plasma was significantly higher,while the level of 6-keto-PGF1α was significantly lower,and platelet aggregation was significantly higher after ADP induction in the model group(P＜0.05).Compared with the model group,the weight of arteriovenous bypass thrombosis in clopidogrel positive control group and QXJYG dose groups was significantly decreased(P＜0.05);the inhibition rate of thrombosis formation was 53.80％,23.96％,33.63％,and 32.59％,respectively.The content of TXB2 in plasma was significantly decreased,the content of 6-keto-PGF1α was significantly increased;additionally,the platelet aggregation rate induced by ADP was reduced in clopidogrel positive control group and QXJYG group.Meanwhile,there was a dose-dependence between different doses in QXJYY group(P＜0.05),and the inhibition rate of platelet aggregation was 86.90％,26.17％,38.87％,54.48％,respectively.Conclusion QXJYG can prevent thrombosis formation in the rat model of arteriovenous bypass thrombosis and inhibit platelet aggregation induced by ADP.

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.

Microneedle percutaneous immunization is achieved by puncturing the stratum corneum of the skin with microneedles so that the vaccine is efficiently recognized by antigen-presenting cells to induce a specific immune response. Due to the advantages of efficient induction of immune response, low pain and easy storage, transdermal immunization by microneedles has been widely used for immunization of various vaccines in recent years. This review summarizes the materials of microneedles, application for transcutaneous immunization, as well as the challenges that need to be addressed.
Administration, Cutaneous ; Drug Delivery Systems ; Needles ; Vaccination ; Vaccines