ObjectiveTo investigate the effects of Astragali Radix polysaccharides （APS） on the polarization of BV2 microglial cells in an oxygen-glucose deprivation/reoxygenation （OGD/R） model through regulation of the Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） signaling pathway. MethodsThe OGD/R injury model of BV2 microglia was established and divided into blank group， OGD/R group and APS group （0.4 g·L^-1 APS）. Neuroinflammatory injury was induced by lipopolysaccharide （LPS） and treated with APS. The cells were divided into blank group， LPS group （1 mg·L^-1 LPS） and APS group （0.4 g·L^-1 APS+1 mg·L^-1 LPS）. Cell viability was detected using the cell counting kit-8 （CCK-8） assay. Cell morphology was observed under an inverted microscope. Nitric oxide （NO） content in the cell supernatant was determined by the Griess assay. The secretion levels of tumor necrosis factor-α （TNF-α）， interleukin （IL）-6， IL-10， and IL-4 were measured by enzyme-linked immunosorbent assay （ELISA）. Immunofluorescence （IF） was used to detect the double-positive rates of ionized calcium-binding adapter molecule-1/inducible nitric oxide synthase （Iba-1⁺/iNOS⁺） and ionized calcium-binding adapter molecule-1/arginase 1 （Iba-1⁺/Arg1⁺）， as well as the nuclear translocation rate of nuclear factor-κB p65 （NF-κB p65）. Protein expression levels of Iba-1， iNOS， Arg1， TLR4， and NF-κB p65 were detected by Western blot. ResultsIn the OGD/R injury model， compared with the blank control group， BV2 microglial cells in the OGD/R group were activated and exhibited amoeboid morphological changes. The secretion levels of NO， TNF-α， and IL-6 were significantly increased （P<0.01）. The double-positive expression rate of Iba-1⁺/iNOS⁺ and the protein expression of Iba-1 and iNOS were significantly increased （P<0.01）. The nuclear translocation rate of NF-κB p65 and the protein expression levels of TLR4 and NF-κB p65 were significantly increased （P<0.01）. The levels of IL-10 and IL-4 were significantly decreased （P<0.01）， and the double-positive expression rate of Iba-1⁺/Arg1⁺ and Arg1 protein expression were significantly decreased （P<0.01）. Compared with the OGD/R group， the APS group （0.4 g·L^-1） showed reduced cell activation， significantly decreased secretion levels of NO， TNF-α， and IL-6 （P<0.01）， significantly decreased double-positive expression rate of Iba-1⁺/iNOS⁺ and relative protein expression of Iba-1 and iNOS （P<0.01）， significantly decreased nuclear translocation rate of NF-κB p65 and protein expression levels of TLR4 and NF-κB p65 （P<0.01）， significantly increased levels of IL-10 and IL-4 （P<0.01）， and significantly increased double-positive expression rate of Iba-1⁺/Arg1⁺ and Arg1 protein expression （P<0.01）. In the LPS-induced neuroinflammation model， compared with the blank control group， the LPS group showed increased cell activation， significantly increased levels of NO， TNF-α， and IL-6， significantly increased Iba-1⁺/iNOS⁺ double-positive expression rate， NF-κB p65 nuclear translocation rate， and protein expression levels of Iba-1， iNOS， TLR4， and NF-κB p65 （P<0.01）， while IL-10 and IL-4 levels， Iba-1⁺/Arg1⁺ double-positive expression rate， and Arg1 protein expression were significantly decreased （P<0.01）. Compared with the LPS group， the APS group showed reduced cell activation， significantly decreased levels of NO， TNF-α， and IL-6， Iba-1⁺/iNOS⁺ double-positive expression rate， NF-κB p65 nuclear translocation rate， and protein expression levels of Iba-1， iNOS， TLR4， and NF-κB p65 （P<0.01）， while IL-10 and IL-4 levels， Iba-1⁺/Arg1⁺ double-positive expression rate， and Arg1 protein expression were significantly increased （P<0.01）. ConclusionAPS may reduce microglial activation and promote their polarization toward the M2 phenotype by inhibiting activation of the TLR4/NF-κB signaling pathway， thereby alleviating the neuroinflammatory response induced by OGD/R.

Clinical death refers to the permanent cessation of life functions. This article reviews the definition of clinical death and the various scenarios in which it occurs, classifies the process of clinical death, and discusses the criteria for determining uncontrollable cardiac death, controllable cardiac death and the criteria and workflow for determining brain death. It elaborates on the relationship between brain death and death, and proposes the areas to note when standardizing the medical documentation of death cases. Based on this, it introduces the content of the management system and workflow construction for death determination in medical institutions, including management structure, personnel qualifications, document norms, quality control system and training mechanism. Paying attention to the construction of the management system and workflow for death determination in medical institutions is of great significance for ensuring medical quality and safety, promoting the healthy development of organ donation, and maintaining the seriousness of legal and ethical practices.

ObjectiveTo investigate the effect of repetitive peripheral magnetic stimulation (rPMS) combined with upper limb intelligent robotic training on muscle tension, motor function and cortical excitability in children with unilateral spastic cerebral palsy (USCP). MethodsFrom March, 2023 to December, 2024, 90 children with USCP admitted to Children's Hospital of Soochow University were selected and randomly divided into control group (n = 30), rPMS group (n = 30) and combined group (n = 30). The control group received conventional occupational therapy. The rPMS group received rPMS intervention followed by conventional occupational therapy. The combined group received rPMS followed by upper limb intelligent robot training, for four weeks. Before and after treatment, muscle tension of biceps brachii was assessed using the modified Ashworth Scale (MAS); upper limb motor function was evaluated using the Fugl-Meyer Assessment-Upper Extremity (FMA-UE) and upper limb intelligent parameters; and cortical excitability was measured using transcranial magnetic stimulation (TMS), including resting motor threshold (RMT) and motor-evoked potential (MEP) amplitude of the affected hemisphere. ResultsAfter treatment, MAS grades improved in all groups (|Z| > 3.523, P < 0.001), and the improvement in the combined group was superior to that in the control group (P < 0.05). Significant intra-group (F > 65.21, P < 0.001), inter-group (F > 17.94, P < 0.001) and interaction effects (F > 5.36, P < 0.01) were observed in FMA-UE scores, upper limb intelligent parameters and TMS parameters. Post Hoc analysis showed that the combined group demonstrated significantly greater improvements in FMA-UE scores, upper limb intelligent parameters, and TMS parameters compared with both the control and rPMS groups (all P < 0.01). Except for FMA-UE scores, the rPMS group showed significantly greater improvements than the control group in upper limb intelligent parameters (mechanical feedback, trajectory, and range of motion) and TMS parameters (RMT and MEP amplitude) (P < 0.05). ConclusionrPMS combined with upper limb intelligent robotic training can reduce upper limb muscle tension, improve motor function, and enhance cortical excitability in children with USCP.

OBJECTIVE To explore the mechanism of the active ingredient compatibility（quercetin， quercitrin and kaempferol at a mass ratio of 2∶9∶3）of Dimocarpus longan Lour. leaves（abbreviated as CDL） on ameliorating glucose and lipid metabolism disorders in type 2 diabetes mellitus （T2DM） rats. METHODS SD rats were randomly divided into blank control group， model group， metformin hydrochloride group （100 mg/kg）， and CDL high-， medium- and low-dose groups （280， 140， 75 mg/kg）， with 10 rats in each group. Rats in the blank control group were fed with standard chow， while rats in the other groups were given high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin to establish the T2DM rat model. After successful modeling， rats in each administration group were given corresponding drug solution， and rats in the blank control group and model group were intragastrically administered with equal volume of pure water， once a day， for consecutive 4 weeks. Fasting blood glucose （FBG） was detected at fixed time every week. The curves of oral glucose tolerance test （OGTT） and intraperitoneal insulin tolerance test （IPITT） were plotted， and the area under curve （AUC） was calculated. The pancreatic islet function indexes [fasting insulin （FINS）， homeostasis model assessment of insulin resistance （HOMA-IR）， insulin sensitivity index （ISI）]，blood lipid indexes [total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）] and hepatic glycogen content were determined. The pathological morphological changes of liver and pancreatic tissues were observed. The protein and mRNA expression levels of molecules related to phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway in liver tissues were detected. RESULTS Compared with the blank control group， the FBG， AUC of IPITT curve， AUC of OGTT curve， HOMA-IR， the levels of FINS， TC， TG and LDL-C， as well as the protein and mRNA expression of phosphatase and tensin homolog， forkhead box protein O1 and glycogen synthase kinase-3β in liver tissues were significantly increased in the model group （ P ＜0.05）. ISI， the levels of HDL-C and hepatic glycogen content， along with the protein and mRNA expression of PI3K， insulin receptor substrate-1， Akt and protein expression of phosphorylated Akt in liver tissues were markedly decreased （ P ＜0.05）. In model group rats， the arrangement of hepatocytes was irregular， the overall structure of pancreatic lobules was disordered， and a large number of inflammatory cell infiltration was observed. Compared with the model group， most of the above quantitative indexes were significantly reversed in the CDL high-dose group （ P ＜0.05）， and the pathological lesions of liver and pancreas were obviously alleviated. CONCLUSIONS CDL can regulate glucose and lipid metabolism disorders， elevate insulin sensitivity and relieve insulin resistance in T2DM rats. Its mechanism may be related to the activation of the PI3K/Akt signaling pathway.

BackgroundBipolar disorder is a severe mental disorder characterized by alternating episodes of mania and depression. It has a high recurrence rate and a high rate of disability. Elderly patients often suffer from more severe cognitive impairment due to neurodegenerative changes. The clinical intervention for bipolar disorder mainly relies on drug treatment， but drugs have limited effects on improving cognitive function， and some drugs may even aggravate cognitive impairment. Aerobic exercise， as a non-drug intervention method， has shown positive effects in improving cognitive function in patients with mental disorders. However， there are still insufficient studies on elderly patients with bipolar disorder. ObjectiveTo explore the impact of aerobic exercise on the cognitive function of elderly patients with bipolar disorder， so as to provide references for the formulation of strategies to improve the cognitive function of this population. MethodsA randomized controlled trial was conducted. A total of 60 elderly patients who were hospitalized at the Third People's Hospital of Lanzhou from January 2024 to March 2025 and met the diagnostic criteria for bipolar disorder as defined in the International Classification of Diseases，tenth edition （ICD-10） were selected. They were divided into the study group and the control group， with 30 cases in each group， based on the random number table method. Both groups were given quetiapine fumarate tablets and magnesium valproate sustained-release tablets. The study group additionally received aerobic exercise （including slow walking， doing exercises， and running）， three times a week， for 30 minutes each time. At the baseline and at the end of the 3^rd， 6^th， 9^th， and 12^th week of the intervention， the Hamilton Depression Scale -24 item （HAMD-24）， the Young Manic Rating Scale （YMRS）， the Montreal Cognitive Assessment （MoCA）， and Wechsler Adult Intelligence Scale Revised in China （WMS-RC） were used for assessment. ResultsThe time effect of the HAMD-24 score was statistically significant （Wald χ²=124.564， P<0.01）. The time effect of the YMRS score was also statistically significant （Wald χ²=145.608， P<0.01）， and the interaction effect between time and group was statistically significant （Wald χ²=14.968， P<0.05）. At the 3^rd， 9^th， and 12^th week of the intervention， the YMRS score of the study group was lower than that of the control group in the same period， and the differences were statistically significant （P<0.05）. The time effect and group effect of the MoCA score were both statistically significant （F=99.347， 16.623， P<0.01）. The time effect， group effect， and interaction effect between time and group of the WMS-RC memory quotient were all statistically significant （F=64.678， 10.197， 12.472， P<0.01）. At the 6^th， 9^th， and 12^th weeks of the intervention， the MoCA score and WMS-RC memory quotient of the study group were higher than those of the control group， and the differences were statistically significant （P<0.05）. ConclusionAerobic exercise may help improve the manic symptoms and cognitive functions （especially memory ability） of elderly patients with bipolar disorder. ［Funded by Science and Technology Project of Gansu Province （number， 24JRRA775）； Science and Technology Project of Lanzhou City（number， 2022-5-155）］

OBJECTIVE To explore the mechanism of the active ingredient compatibility（quercetin， quercitrin and kaempferol at a mass ratio of 2∶9∶3）of Dimocarpus longan Lour. leaves（abbreviated as CDL） on ameliorating glucose and lipid metabolism disorders in type 2 diabetes mellitus （T2DM） rats. METHODS SD rats were randomly divided into blank control group， model group， metformin hydrochloride group （100 mg/kg）， and CDL high-， medium- and low-dose groups （280， 140， 75 mg/kg）， with 10 rats in each group. Rats in the blank control group were fed with standard chow， while rats in the other groups were given high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin to establish the T2DM rat model. After successful modeling， rats in each administration group were given corresponding drug solution， and rats in the blank control group and model group were intragastrically administered with equal volume of pure water， once a day， for consecutive 4 weeks. Fasting blood glucose （FBG） was detected at fixed time every week. The curves of oral glucose tolerance test （OGTT） and intraperitoneal insulin tolerance test （IPITT） were plotted， and the area under curve （AUC） was calculated. The pancreatic islet function indexes [fasting insulin （FINS）， homeostasis model assessment of insulin resistance （HOMA-IR）， insulin sensitivity index （ISI）]，blood lipid indexes [total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）] and hepatic glycogen content were determined. The pathological morphological changes of liver and pancreatic tissues were observed. The protein and mRNA expression levels of molecules related to phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway in liver tissues were detected. RESULTS Compared with the blank control group， the FBG， AUC of IPITT curve， AUC of OGTT curve， HOMA-IR， the levels of FINS， TC， TG and LDL-C， as well as the protein and mRNA expression of phosphatase and tensin homolog， forkhead box protein O1 and glycogen synthase kinase-3β in liver tissues were significantly increased in the model group （ P ＜0.05）. ISI， the levels of HDL-C and hepatic glycogen content， along with the protein and mRNA expression of PI3K， insulin receptor substrate-1， Akt and protein expression of phosphorylated Akt in liver tissues were markedly decreased （ P ＜0.05）. In model group rats， the arrangement of hepatocytes was irregular， the overall structure of pancreatic lobules was disordered， and a large number of inflammatory cell infiltration was observed. Compared with the model group， most of the above quantitative indexes were significantly reversed in the CDL high-dose group （ P ＜0.05）， and the pathological lesions of liver and pancreas were obviously alleviated. CONCLUSIONS CDL can regulate glucose and lipid metabolism disorders， elevate insulin sensitivity and relieve insulin resistance in T2DM rats. Its mechanism may be related to the activation of the PI3K/Akt signaling pathway.

ObjectiveThis study aims to develop a prediction model for the compatibility of Chinese medicinal pairs based on Graph Convolutional Networks （GCN）， named HC-GCN. The model integrates the properties of herbs with modern pharmacological mechanisms to predict pairs with specific therapeutic effects. It serves as a demonstration by applying the model to predict and validate the efficacy of blood-activating herb pairs. MethodsThe training dataset for herb pair prediction was constructed by systematically collecting commonly used herb pairs along with their characteristic data， including Qi， flavor， meridian tropism， and target genes. Integrating traditional characteristics of herb with modern bioinformatics， we developed an efficacy-oriented herb pair compatibility prediction model （HC-GCN） using graph convolutional networks （GCN）. This model leverages machine learning to capture the complex relationships in herb pair compatibility， weighted by efficacy features. The performance of the HC-GCN model was evaluated using accuracy （ACC）， recall， precision， F1 score （F1）， and area under the ROC curve （AUC）. Its predictive effectiveness was then compared to five other machine learning models： eXtreme Gradient Boosting （XGBoost）， logistic regression （LR）， Naive Bayes， K-nearest neighbor （KNN）， and support vector machine （SVM）. ResultsUsing herb pairs with blood-activating effects as a demonstration， a prediction model was constructed based on a foundational dataset of 46 blood-activating herb pairs， incorporating their Qi， flavor， meridian tropism， and target gene characteristics. The HC-GCN model outperforms other commonly used machine learning models in key performance metrics， including ACC， recall， precision， F1 score， and AUC. Through the predictive analysis of the HC-GCN model， 60 herb pairs with blood-activating effects were successfully identified. Among of these potential herb pairs， 44 include at least one herb with blood-activating effects. ConclusionIn this study， we established an efficacy-oriented compatibility prediction model for herb pairs based on GCN by integrating the unique characteristics of traditional herbs with modern pharmacological mechanisms. This model demonstrated high predictive performance， offering a novel approach for the intelligent screening and optimization of traditional Chinese medicine prescriptions， as well as their clinical applications.

Severe pneumonia is one of the most common and critical respiratory diseases in clinical practice. It is characterized by rapid progression， difficult treatment， high mortality， and many complications， posing a significant threat to the life and health of patients. The pathogenesis of severe pneumonia is highly complex， and studies have shown that its occurrence and development are closely related to multiple signaling pathways. Currently， the treatment of severe pneumonia mainly focuses on anti-infection， mechanical ventilation， and glucocorticoids， but clinical outcomes are often not ideal. Therefore， finding safe and effective alternative therapies is particularly important. In recent years， with the deepening of research into traditional Chinese medicine （TCM）， it has gained widespread attention in the treatment of severe pneumonia. This paper reviewed the relationship between severe pneumonia and relevant signaling pathways in recent years and how TCM regulated these pathways in the treatment of severe pneumonia. It was found that TCM could regulate the Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-κB （NF-κB）， Janus kinase （JAK）/signal transducer and activator of transcription （STAT）， phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR）， NOD-like receptor protein 3 （NLRP3）， and nuclear factor E₂-related factor 2 （Nrf2） signaling pathways， playing a role in reducing the inflammatory response， inhibiting cell apoptosis and pyroptosis， improving oxidative stress， and other effects in the treatment of severe pneumonia. Among these pathways， it was found that all of them regulated inflammation to treat severe pneumonia. Therefore， reducing inflammation is the core mechanism by which Chinese medicine treats severe pneumonia. This review provides direction for the clinical treatment of severe pneumonia and offers a scientific basis for the research and development of new drugs.

ObjectiveTo investigate the role and mechanism of Go-Ichi-Ni-San complex subunit 1 （GINS1） in the progression of hepatocellular carcinoma （HCC） and the development of chemotherapy resistance. MethodsThe tumor database GEPIA2 was used to analyze the differential expression of GINS1 between HCC patients and healthy individuals， and pathological tissue samples were collected from 40 HCC patients who were admitted to The Affiliated Tumor Hospital of Xinjiang Medical University and the First Affiliated Hospital of Xinjiang Medical University from May 2017 to January 2021. Immunohistochemical staining was used to measure the difference in the expression of GINS1 between HCC tissue and corresponding adjacent tissue， and the correlation between the expression level of GINS1 and the clinical TNM stage of HCC was analyzed. Western blot was also used to measure the difference in the expression of GINS1 between HCC Huh7/Hep3B/Li-7/MHCC97H cell lines and normal human QSG7701 hepatocytes. The method of lentivirus transfection was used to establish the MHCC97H cell line with stable GINS1 knockdown and its negative control cell line. CCK-8 assay and colony formation assay were used to measure cell proliferative capacity； scratch assay was used to measure cell migration ability； Transwell assay was used to measure cell invasion ability； cells were treated with oxaliplatin to measure their sensitivity to chemotherapy drugs. Nude mice were used to establish a tumor-bearing model and observe the effect of GINS1 knockdown on the growth of HCC in vivo. Western Blot was used to measure the expression levels of the proteins associated with the Notch pathway and the JAK/STAT pathway. The cells were treated with the Notch receptor agonist Jagged-1 to analyze the association between GINS1 and the Notch/JAK/STAT pathway. The independent-samples t test was used for comparison of continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsThe expression of GINS1 was upregulated in HCC patients， HCC tissue， and HCC cell lines （all P<0.05）， and the expression level of GINS1 was positively correlated with the clinical TNM stage of HCC （r=0.822， P=0.011）. Compared with the negative control cells， the GINS1-knockdown MHCC97H cells showed significant reductions in proliferation， migration， and invasion activities （all P<0.01） and a significantly enhanced sensitivity to oxaliplatin （P<0.01）. Compared with the nude mice in the control group， GINS1 knockdown caused significant inhibition of tumor weight and volume in vivo in nude mice （all P<0.001）. Compared with the negative control cells， the GINS1-knockdown MHCC97H cells showed significant reductions in the expression levels of Notch1， Notch3， p-JAK2， and p-STAT3 （all P<0.05）， while there were no significant differences in the overall expression levels of JAK2 and STAT3 （P>0.05）. After Jagged-1 treatment， the GINS1-knockdown MHCC97H cells showed significant increases in proliferation， migration， and invasion activities and a significant reduction in sensitivity to oxaliplatin， as well as significant increases in the levels of p-JAK2 and p-STAT3 （all P<0.05）. ConclusionGINS1 is upregulated in HCC and can promote HCC progression and chemotherapy resistance through the Notch/JAK2/STAT3 pathway.

With the rapid development of mobile internet technology, mobile health application (mHealth APP) are increasingly widely used in the field of health management and have been proven to play an important role in the management of chronic diseases. Solid organ transplant recipients face complex health management needs after surgery, including postoperative follow-up, medication management, prevention and treatment of complications and comorbidities, and lifestyle adjustment. mHealth APP can provide solid organ transplant recipients with convenient self-management tools. Although some progress has been made in this field, there are still many challenges, such as insufficient user experience, technological dependence, and data security risks. Therefore, this article discusses the development process, main functions and current application status of mHealth APP, and analyzes its advantages in improving the self-management ability of solid organ transplant recipients, promoting doctor-patient communication and reducing the incidence of complications. At the same time, based on the practical experience of author’s team in developing the “TransMate” mHealth APP, we propose the directions that mHealth APPs should focus on in the future, in order to provide more effective support and services for the health management of solid organ transplant recipients.