ObjectiveTo explore the mechanism by which Banxia Xiexin Tang （BXT） regulates the advanced glycation end products （AGE）/receptor for advanced glycation end products （RAGE） signaling pathway to reduce neuroinflammatory responses and ameliorate cognitive dysfunction in the rat model of vascular dementia （VD）. MethodsThe components of BXT were detected by ultra performance liquid chromatography-quadrupole -orbitrap-tandem mass spectrometry（UPLC-Q-Orbitrap-MS/MS）， and the core components and key action pathways were screened out by network pharmacology and molecular docking. Sixty SPF-grade male SD rats were randomly allocated into the sham and modeling groups by the random number table method. The VD model was replicated by the modified bilateral occlusion of the common carotid arteries （2-VO） method. The successfully modeled rats were randomly allocated into the model， low-， medium-， and high-dose （3.748 5， 7.497， 14.994 g·kg^-1） BXT （BXT-L， BXT-M， and BXT-H）， and nimodipine （NMP， 0.002 7 g·kg^-1） groups according to the random number table method. The rats in the drug intervention groups were administrated with corresponding drugs by gavage， and the sham and model groups received the same amount of normal saline for 14 consecutive days. The Morris water maze， Y-maze， and new object recognition experiments were conducted to evaluate the cognitive dysfunction of rats. Hematoxylin-eosin （HE） staining was used to evaluate the histopathological changes of the hippocampal tissue in rats. The mRNA levels of AGE， RAGE， and phosphorylated nuclear factor-kappa B p65 （p-NF-κB p65） in the hippocampal tissue of rats were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expression of related proteins in the AGE/RAGE pathway in the hippocampal tissue of rats was determined by Western blot and immunohistochemistry （IHC）. The levels of neurotransmitters and inflammatory mediators in the rat serum were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsThe chemical components of BXT were detected by UPLC-Q-Orbitrap-MS/MS. Network pharmacology and molecular docking identified the AGE/RAGE pathway as the key pathway. The results of the water maze， Y maze， and novel object recognition tests showed that compared with the sham group， the model group demonstrated prolonged successful latency and decreases in number of platform crossings， alternation rate， number of entries into the new arm， preference index， and discrimination index （P0.01）. Compared with the model group， the BXT-H and BXT-M groups showed shortened successful latency （P0.01） and increases in number of platform crossings （P0.05）， alternation rate （P0.01）， number of entries into the new arm （P0.05）， preference index （P0.01）， and discrimination index （P0.01）. HE results showed that compared with the sham group， the cells of model rats were loosely and disorderly arranged， and the nuclei were condensed. Compared with the model group， the pathological changes of the hippocampus in the BXT group were mitigated. Real-time PCR results showed that compared with the sham group， the model group presented up-regulated mRNA levels of AGE， RAGE， and p-NF-κB p65 in the hippocampus （P0.01）， and compared with the model group， the BXT-H and BXT-M groups showcased down-regulated mRNA levels of AGE， RAGE， and p-NF-κB p65 （P0.01）. Western blot results showed that compared with the sham group， the model group presented up-regulated expression of AGE， RAGE， p-NF-κB p65， and tumor necrosis factor-α （TNF-α） （P0.05）， and compared with the model group， the BXT-H group presented down-regulated expression of AGE， RAGE， p-NF-κB p65， and TNF-α （P0.05）. IHC results showed that compared with the sham group， the model group had increased expression of RAGE （P0.01）， and compared with the model group， the BXT-H and BXT-M groups had reduced expression of RAGE （P0.01）. ELISA results showed that compared with the sham group， the model group exhibited elevated levels of TNF-α and Interleukin-1β （IL-1β） and declined levels of acetylcholine （ACh） and dopamine （DA） in the serum （P0.01）. Compared with the model group， the BXT-L， BXT-M， and BXT-H groups showed lowered levels of TNF-α and IL-1β in the serum （P0.05） and elevated levels of ACh and DA （P0.05）. ConclusionBXT may ameliorate cognitive dysfunction in the rat model of VD by down-regulating the AGE/RAGE signaling pathway， reducing neuroinflammatory responses， and regulating neurotransmitter levels.

Insomnia is a sleep disorder characterized by difficulty in falling asleep， sleep maintenance disorder and impaired daytime function. Its pathological mechanism involves multiple factors such as nerve excitability， circadian rhythm， cell apoptosis， oxidative stress injury. As a classical tyrosine kinase signaling pathway， phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt） triggers Akt phosphorylation cascade， inducing inflammatory response， apoptosis， autophagy， oxidative damage， nerve excitability， and circadian rhythm imbalance. Traditional Chinese medicine（TCM） can improve sleep by targeting the PI3K/Akt pathway. Based on this， this paper systematically reviews the research progress on the regulation of PI3K/Akt pathway by traditional Chinese medicine（TCM） for insomnia at home and abroad. These drugs can regulate neuronal excitability by regulating the PI3K/Akt pathway， affect the circadian rhythm， alleviate inflammation， apoptosis， autophagy and oxidative stress， and thus regulate sleep-wake. Furthermore， literature review indicates that the PI3K/Akt signaling pathway may represent a specific pathway underlying phlegm-turbidity disturbing the upper Jiao-type insomnia.

ObjectiveTo explore the mechanism by which Banxia Xiexin Tang （BXT） regulates the advanced glycation end products （AGE）/receptor for advanced glycation end products （RAGE） signaling pathway to reduce neuroinflammatory responses and ameliorate cognitive dysfunction in the rat model of vascular dementia （VD）. MethodsThe components of BXT were detected by ultra performance liquid chromatography-quadrupole -orbitrap-tandem mass spectrometry（UPLC-Q-Orbitrap-MS/MS）， and the core components and key action pathways were screened out by network pharmacology and molecular docking. Sixty SPF-grade male SD rats were randomly allocated into the sham and modeling groups by the random number table method. The VD model was replicated by the modified bilateral occlusion of the common carotid arteries （2-VO） method. The successfully modeled rats were randomly allocated into the model， low-， medium-， and high-dose （3.748 5， 7.497， 14.994 g·kg^-1） BXT （BXT-L， BXT-M， and BXT-H）， and nimodipine （NMP， 0.002 7 g·kg^-1） groups according to the random number table method. The rats in the drug intervention groups were administrated with corresponding drugs by gavage， and the sham and model groups received the same amount of normal saline for 14 consecutive days. The Morris water maze， Y-maze， and new object recognition experiments were conducted to evaluate the cognitive dysfunction of rats. Hematoxylin-eosin （HE） staining was used to evaluate the histopathological changes of the hippocampal tissue in rats. The mRNA levels of AGE， RAGE， and phosphorylated nuclear factor-kappa B p65 （p-NF-κB p65） in the hippocampal tissue of rats were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The expression of related proteins in the AGE/RAGE pathway in the hippocampal tissue of rats was determined by Western blot and immunohistochemistry （IHC）. The levels of neurotransmitters and inflammatory mediators in the rat serum were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsThe chemical components of BXT were detected by UPLC-Q-Orbitrap-MS/MS. Network pharmacology and molecular docking identified the AGE/RAGE pathway as the key pathway. The results of the water maze， Y maze， and novel object recognition tests showed that compared with the sham group， the model group demonstrated prolonged successful latency and decreases in number of platform crossings， alternation rate， number of entries into the new arm， preference index， and discrimination index （P<0.01）. Compared with the model group， the BXT-H and BXT-M groups showed shortened successful latency （P<0.01） and increases in number of platform crossings （P<0.05）， alternation rate （P<0.01）， number of entries into the new arm （P<0.05）， preference index （P<0.01）， and discrimination index （P<0.01）. HE results showed that compared with the sham group， the cells of model rats were loosely and disorderly arranged， and the nuclei were condensed. Compared with the model group， the pathological changes of the hippocampus in the BXT group were mitigated. Real-time PCR results showed that compared with the sham group， the model group presented up-regulated mRNA levels of AGE， RAGE， and p-NF-κB p65 in the hippocampus （P<0.01）， and compared with the model group， the BXT-H and BXT-M groups showcased down-regulated mRNA levels of AGE， RAGE， and p-NF-κB p65 （P<0.01）. Western blot results showed that compared with the sham group， the model group presented up-regulated expression of AGE， RAGE， p-NF-κB p65， and tumor necrosis factor-α （TNF-α） （P<0.05）， and compared with the model group， the BXT-H group presented down-regulated expression of AGE， RAGE， p-NF-κB p65， and TNF-α （P<0.05）. IHC results showed that compared with the sham group， the model group had increased expression of RAGE （P<0.01）， and compared with the model group， the BXT-H and BXT-M groups had reduced expression of RAGE （P<0.01）. ELISA results showed that compared with the sham group， the model group exhibited elevated levels of TNF-α and Interleukin-1β （IL-1β） and declined levels of acetylcholine （ACh） and dopamine （DA） in the serum （P<0.01）. Compared with the model group， the BXT-L， BXT-M， and BXT-H groups showed lowered levels of TNF-α and IL-1β in the serum （P<0.05） and elevated levels of ACh and DA （P<0.05）. ConclusionBXT may ameliorate cognitive dysfunction in the rat model of VD by down-regulating the AGE/RAGE signaling pathway， reducing neuroinflammatory responses， and regulating neurotransmitter levels.

Insomnia is a sleep disorder characterized by difficulty in falling asleep， sleep maintenance disorder and impaired daytime function. Its pathological mechanism involves multiple factors such as nerve excitability， circadian rhythm， cell apoptosis， oxidative stress injury. As a classical tyrosine kinase signaling pathway， phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt） triggers Akt phosphorylation cascade， inducing inflammatory response， apoptosis， autophagy， oxidative damage， nerve excitability， and circadian rhythm imbalance. Traditional Chinese medicine（TCM） can improve sleep by targeting the PI3K/Akt pathway. Based on this， this paper systematically reviews the research progress on the regulation of PI3K/Akt pathway by traditional Chinese medicine（TCM） for insomnia at home and abroad. These drugs can regulate neuronal excitability by regulating the PI3K/Akt pathway， affect the circadian rhythm， alleviate inflammation， apoptosis， autophagy and oxidative stress， and thus regulate sleep-wake. Furthermore， literature review indicates that the PI3K/Akt signaling pathway may represent a specific pathway underlying phlegm-turbidity disturbing the upper Jiao-type insomnia.

Organ transplantation is an effective alternative treatment for patients with end-stage organ failure. However, the shortage of donor organs has limited the widespread application of clinical transplantation. In recent years, breakthroughs in CRISPR-Cas9 gene editing technology have overcome the barrier of hyperacute rejection in xenotransplantation, offering a potential solution to the organ shortage crisis. Rejection remains a critical factor affecting graft survival. Antigen-presenting cells play a vital role in the initiation and progression of rejection and immune regulation in xenotransplantation. Therefore, in-depth investigation into the role of antigen-presenting cells in xenotransplantation is of great significance. This article summarizes the roles and therapeutic strategies of professional antigen-presenting cells, including macrophages, dendritic cells and B cells in xenotransplantation, aiming to provide insights for future research on immune regulation mechanisms in this field.

Objective To assess the current status and outcomes of living donor liver transplantation (LDLT) in patients with unresectable colorectal cancer liver metastases (CRLM). Methods Two reviewers independently conducted a systematic search of Medline (via PubMed), the Cochrane Library, and ClinicalTrials.gov in accordance with preferred reporting items for systematic reviews guidelines. English-language publications reporting LDLT for unresectable CRLM were identified; study characteristics and recipient outcomes were extracted. Results Twelve studies were retrieved, six completed studies enrolling 55 patients and six ongoing trials. Selected patients appeared to derive benefit from LDLT. Reported overall survival was 100% at 1 year and 100%, 71.4% at 3 years. The 1-year progression-free survival was 85.7% and 75.1%, and 3-year progression-free survival was 68.6% and 53.7%. Conclusions Prospective data on LDLT for unresectable CRLM remain scarce. The approach is still investigational and warrants validation through prospective clinical trials.

OBJECTIVE To provide reference for improving the pre-prescription review system and reducing the occurrence of medication error by analyzing the drug-related problems （DRPs） in the pre-prescription review orders of pediatric outpatient clinics using the Pharmaceutical Care Network Europe （PCNE） classification system. METHODS The data of pre-prescription review orders were retrospectively collected from outpatient department of Shanghai Children’s Medical Center， Shanghai Jiao Tong University School of Medicine from July 2022 to June 2023； DRPs in the pre-prescription review orders were classified and summarized by using the PCNE classification system （version 9.1）， and then analyzed in terms of types and causes of issues， and the acceptance of interventions. RESULTS A total of 66 017 DRPs orders were included， involving 41 165 patients. The proportion of DRPs orders in children aged ≤5 years old was the highest （58.25%）， followed by children aged 6-12 years old （33.52%）； the department with the highest proportion of DRPs was internal medicine of pediatrics department （71.41%）； the department with the highest incidence of DRPs was thoracic surgery department （9.73%）； top three drug categories of DRPs orders were systemic anti- infective drugs （25.26%）， Chinese patent medicines （24.74%） and respiratory drugs （22.38%）. Referring to PCNE classification system， the types of DRPs mainly focused on treatment safety （64.86%）； the reasons of DRPs orders mainly focused on dose selection （82.09%）， of which 41.26% were due to excessive drug dosage； 92.13% of interventions could be accepted and fully executed by doctors. CONCLUSIONS DRPs orders identified by the pre-prescription review system can be effectively analyzed by using PCNE classification system. Pharmacists should focus on medication use in children aged ≤5 years old， update and develop personalized prescription review rules timely， and meet the rational needs of clinical medication for children.

Objective To investigate the correlation between insulin resistance and interleukin-6 (IL-6), chemerin, total cholesterol (TC)/high density lipoprotein cholesterol (HDL-C) ratio, triglyceride (TG)/HDL-C ratio, low density lipoprotein cholesterol (LDL-C)/HDL-C ratio and insulin resistance in obese patients with type 2 diabetes mellitus (T2DM), and to provide scientific basis for T2DM prevention and control. Methods A total of 355 obese T2DM patients in Songjiang Hospital Affiliated to Shanghai Jiaotong University School of Medicine were selected from January 2021 to December 2023. IL-6, chemerin and lipids were detected, and the assessment of insulin resistance was conducted through the homeostasis model assessment of insulin resistance (HOMA-IR). Results Among the 355 obese T2DM patients, there were 280 cases of insulin resistance, with the incidence rate of 78.87%. The BMI, IL-6, chemerin, TC/HDL-C, LDL-C/HDL-C, and TG/HDL-C in the insulin resistance group were higher than those in the non-insulin resistance group (P<0.05). The above insulin resistant patients were divided into 4 subgroups by means of insulin resistance, and there were significant differences in BMI, IL-6, chemerin, and TG/HDL-C among the subgroups (P<0.05). IL-6, chemerin, and TG/HDL-C were positively correlated with HOMA-IR in obese T2DM patients (P<0.05), while TC/HDL-C and LDL-C/HDL-C had no significant correlation with HOMA-IR (P>0.05). BMI, IL-6, chemerin, and TG/HDL-C were all influencing factors of insulin resistance in obese T2DM patients (P<0.05). Conclusion IL-6, chemerin and TG/HDL-C are correlated with insulin resistance in obese patients with T2DM and are influencing factors for the occurrence of insulin resistance.

Myopia is a common eye disease among children and adolescents, and it is also a major and common public health problem for children and adolescents worldwide. Although the myopia rate among children and adolescents in different provinces , cities , and regions varies , the incidence of myopia is generally high , showing a trend of high incidence and younger age. Myopia in children and adolescents is closely related to sleep conditions . The sleep time of most children and adolescents in China does not reach the recommended length of time for this age group, and their sleep quality is poor, which affects their study and life. The biological connection and molecular mechanism between sleep and myopia are hot topics in clinical research . This article reviews the epidemiological characteristics of myopia and sleep status in children and adolescents , as well as the biological mechanisms between sleep and myopia , with the aim of providing a theoretical basis for preventing myopia in children and adolescents.

N-acetyl-p-aminophenol （APAP） is an antipyretic analgesic commonly used in clinical practice， and APAP overdose can cause severe liver injury and even death. In recent years， the incidence rate of APAP-induced liver injury （AILI） tends to increase， and it has become the second most common cause of liver transplantation worldwide. Autophagy is a highly conserved catabolic process that removes unwanted cytosolic proteins and organelles through lysosomal degradation to achieve the metabolic needs of cells themselves and the renewal of organelles. A large number of studies have shown that autophagy plays a key role in the pathophysiology of AILI， involving the mechanisms such as APAP protein conjugates， oxidative stress， JNK activation， mitochondrial dysfunction， inflammatory response and apoptosis. This article elaborates on the biological mechanism of autophagy in AILI， in order to provide a theoretical basis for the treatment of AILI and the development of autophagy regulators.