ObjectiveBased on the clinical characteristics of chronic gouty arthritis （CGA） in both traditional Chinese and western medicine， this study aims to systematically evaluate the clinical concordance of existing CGA animal models， providing recommendations for establishing animal models that align with the pathological characteristics of CGA and the manifestations of traditional Chinese medicine syndromes. MethodsBy comprehensively retrieving Chinese and international databases such as China National Knowledge Infrastructure， Wanfang， VIP Chinese Science and Technology Periodical Database （VIP）， and PubMed， all relevant literature on CGA animal models was collected. Based on the guidelines， the diagnostic criteria of both traditional Chinese and western medicine were summarized and organized. The evaluation indicators for the CGA model were constructed with reference to existing evaluation modes， and the CGA animal models were analyzed to systematically evaluate the clinical concordance of existing models. ResultsThe current methods used to construct CGA animal models mainly include monosodium urate crystal induction， high-protein diet induction （poultry lack urate oxidase）， and high-fat diet combined with urate oxidase inhibitors and joint injection. Based on 11 pieces of included literature， the traditional Chinese and western medicine scoring data of each model were extracted， and the average scoring values of all models were ultimately calculated. The results show that the average clinical concordances of existing CGA animal models in both traditional Chinese and western medicine are 43.33% and 64.44%， respectively. Among them， the model with the highest clinical concordance rate is the one with a high-fat diet combined with potassium oxonate to induce hyperuricemia plus joint injection， achieving 83.33% clinical concordance in western medicine and 60% in traditional Chinese medicine. This model aligns well with the pathogenic characteristics and pathological changes of clinical CGA. ConclusionAlthough current CGA animal models can simulate some pathological characteristics of CGA， they struggle to comprehensively reflect the complex pathological processes of CGA and the characteristics of traditional Chinese medicine syndromes. Therefore， in the future， it is necessary to establish the CGA animal models that incorporate the clinical disease and syndrome characteristics of traditional Chinese and western medicine and formulate the uniform model evaluation criteria， providing more precise tools for CGA mechanism research and the development of traditional Chinese medicine.

OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.

Functional constipation （FC） is a clinically common functional bowel disorder characterized by a protracted course and associations with various chronic disorders and psychological abnormalities. Although not life-threatening， FC significantly impairs patients' quality of life. FC subtypes include slow-transit constipation （STC）， defecatory disorder （DD）， and normal-transit constipation （NTC）. The pathological mechanisms underlying FC have not been fully elucidated， and overall clinical efficacy remains unsatisfactory. Animal models of FC serve as essential tools for the study of disease mechanisms and the development of novel therapeutics. This article systematically reviews the current state of research on the animal models of FC and identifies that rodents， particularly rats and mice， are the most commonly used species. Dogs and pigs are also employed in complex intervention studies due to their physiological similarities to humans， though their use is limited by housing challenges and ethical considerations. Induction methods vary across different FC subtypes. STC models are primarily established with chemical agents such as loperamide or compound diphenoxylate. DD modeling often involves low-fiber diets combined with methylene blue injection or rectal narrowing. NTC modeling mainly relies on low-fiber dietary interventions. In addition， disease-syndrome combination models based on traditional Chinese medicine （TCM） theory have been developed， encompassing excess patterns such as heat accumulation， cold accumulation， and Qi stagnation， as well as deficiency patterns including Qi deficiency， blood deficiency， Yin deficiency， and Yang deficiency. These are achieved through an approach of disease model + syndrome induction， enabling the integration of mechanisms from both Western and TCM perspectives. Models are evaluated from two aspects： disease and syndrome manifestations （e.g.， colonic transit， secretory function， and TCM syndrome indicators such as mental state and body weight） and disease mechanisms （e.g.， enteric nervous system， interstitial cells of Cajal， smooth muscle cells， gut microbiota， and metabolites）. However， current research still faces challenges such as poor consistency in some models， non-specific interference in mechanism interpretation， insufficient studies on NTC， and lack of TCM tongue and pulse diagnosis in evaluation. Future efforts should focus on optimizing model stability and specificity to provide a more reliable experimental basis for investigating the pathological mechanisms of FC and developing therapeutic agents.

Clinical trials represent a pivotal stage in the development of pharmaceutical drugs. Nevertheless， given the unique characteristics of traditional Chinese medicine （TCM） and the diagnostic and treatment principle of syndrome differentiation and treatment in TCM， the clinical evaluation techniques and methods that can comprehensively reflect the characteristics of TCM and are tailored to its specificities are still in need of refinement and innovation. This paper systematically summarizes the key techniques and methods for designing and evaluating the clinical research on the treatment of the spleen and stomach diseases with TCM from three aspects including clinical research design， evaluation， and platform construction， compares domestic and international research landscapes， and proposes for future directions. It is suggested that a multidimensional evaluation system integrating modern medicine and TCM theory should be established， and further innovation is needed in TCM research design and methodologies， leveraging intelligent devices and technologies powered by next-generation information technology to transform clinical data into high-quality TCM evidence. Moreover， standardized and shared platforms for TCM clinical data should be accelerated， so as to provide references for the design， implementation， and evaluation of future clinical research on the treatment of the spleen and stomach diseases with TCM.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

Alzheimer’s disease (AD) is a chronic neurodegenerative disorder that severely affects the health of the elderly, marked by its incurability, high prevalence, and extended latency period. The current approach to AD prevention and treatment emphasizes early detection and intervention, particularly during the pre-AD stage of mild cognitive impairment (MCI), which provides an optimal “window of opportunity” for intervention. Clinical detection methods for MCI, such as cerebrospinal fluid monitoring, genetic testing, and imaging diagnostics, are invasive and costly, limiting their broad clinical application. Speech, as a vital cognitive output, offers a new perspective and tool for computer-assisted analysis and screening of cognitive decline. This is because elderly individuals with cognitive decline exhibit distinct characteristics in semantic and audio information, such as reduced lexical richness, decreased speech coherence and conciseness, and declines in speech rate, voice rhythm, and hesitation rates. The objective presence of these semantic and audio characteristics lays the groundwork for computer-based screening of cognitive decline. Speech information is primarily sourced from databases or collected through tasks involving spontaneous speech, semantic fluency, and reading, followed by analysis using computer models. Spontaneous language tasks include dialogues/interviews, event descriptions, narrative recall, and picture descriptions. Semantic fluency tasks assess controlled retrieval of vocabulary items, requiring participants to extract information at the word level during lexical search. Reading tasks involve participants reading a passage aloud. Summarizing past research, the speech characteristics of the elderly can be divided into two major categories: semantic information and audio information. Semantic information focuses on the meaning of speech across different tasks, highlighting differences in vocabulary and text content in cognitive impairment. Overall, discourse pragmatic disorders in AD can be studied along three dimensions: cohesion, coherence, and conciseness. Cohesion mainly examines the use of vocabulary by participants, with a reduction in the use of nouns, pronouns, verbs, and adjectives in AD patients. Coherence assesses the ability of participants to maintain topics, with a decrease in the number of subordinate clauses in AD patients. Conciseness evaluates the information density of participants, with AD patients producing shorter texts with less information compared to normal elderly individuals. Audio information focuses on acoustic features that are difficult for the human ear to detect. There is a significant degradation in temporal parameters in the later stages of cognitive impairment; AD patients require more time to read the same paragraph, have longer vocalization times, and produce more pauses or silent parts in their spontaneous speech signals compared to normal individuals. Researchers have extracted audio and speech features, developing independent systems for each set of features, achieving an accuracy rate of 82% for both, which increases to 86% when both types of features are combined, demonstrating the advantage of integrating audio and speech information. Currently, deep learning and machine learning are the main methods used for information analysis. The overall diagnostic accuracy rate for AD exceeds 80%, and the diagnostic accuracy rate for MCI also exceeds 80%, indicating significant potential. Deep learning techniques require substantial data support, necessitating future expansion of database scale and continuous algorithm upgrades to transition from laboratory research to practical product implementation.

With the continuous development of society, a large number of new chemicals are continuously emerging, which presents a challenge to current risk assessment and safety management of chemicals. Traditional toxicology research methods have certain limitations in quickly, efficiently, and accurately assessing the toxicity of many chemicals, and cannot meet the actual needs. In response to this challenge, computational toxicology that use mathematical and computer models to achieve the prediction of chemical toxicity has emerged. In the meantime, as researchers increasingly pay attention to understanding the interaction mechanisms between exogenous chemical substances and the body from the system level, and multiomics technologies develop rapidly such as genomics, transcriptomics, proteomics, and metabolomics, huge amounts of data have been generated, providing rich information resources for studying the interactions between chemical substances and biological molecules. System toxicology and network toxicology have also developed accordingly. Of these, network toxicology can integrate these multiomics data to construct biomolecular networks, and then quickly predict the key toxicological targets and pathways of chemicals at the molecular level. This paper outlined the concept and development of network toxicology, summarized the main methods and supporting tools of network toxicology research, expounded the application status of network toxicology in studying potential toxicity of exogenous chemicals such as agricultural chemicals, environmental pollutants, industrial chemicals, and foodborne chemicals, and analyzed the development prospects and limitations of network toxicology research. This paper aimed to provide a reference for the application of network toxicology in other fields.

BACKGROUND:Magnetic nanomaterials have biological activities such as promoting osteogenic differentiation of stem cells and inhibiting osteoclast formation,and can effectively promote the healing of injured bone tissue under the synergistic effect of magnetic fields.They have a very broad application prospect in bone injury repair. OBJECTIVE:To review the mechanism of magnetic nanomaterials and magnetic fields promoting bone repair,as well as their research progress in the field of bone injury repair. METHODS:Relevant literature search was conducted in PubMed and Web of Science databases with the search terms"magnetic nanomaterials,magnetic field,bone repair,bone tissue engineering,stem cell,osteoblast,osteoclast."The time limit of literature search was from 2003 to 2023,which was screened and analyzed.Some classic articles were manually retrieved,and 98 articles were finally included for analysis. RESULTS AND CONCLUSION:(1)Magnetic nanomaterials have biological effects such as promoting osteoblast differentiation,inhibiting osteoclast formation and regulating the immune microenvironment.In addition,magnetic nanomaterials can regulate the physicochemical properties of tissue engineering scaffolds,such as mechanical properties and surface morphology,and endowed with magnetic properties,which is conducive to the regulation of the adhesion,proliferation and osteogenic differentiation of stem cells.(2)The magnetic field has the ability to regulate multiple cell signaling pathways to promote osteoblast differentiation,inhibit osteoclast formation,stimulate angiogenesis and other biological effects,thus accelerating the healing of damaged bone tissue.(3)The joint application of magnetic nanomaterials and magnetic field accelerates the repair of bone damage by activating mechanotransduction,increasing the content of intracellular magnetic nanoparticles,and enhancing the effect of micro-magnetic field,which provides a new idea for the research of bone tissue engineering.(4)Magnetic field has demonstrated definite efficacy in the treatment of clinical fractures,osteoporosis,and osteoarthritis diseases,which is beneficial for bone tissue growth,reducing bone loss,alleviating pain,and improving the quality of life of patients.(5)Magnetic nanomaterials and magnetic fields have great potential for application in bone damage repair and regeneration,but the interaction mechanism between magnetic nanomaterials,magnetic fields,and cells has not been fully elucidated.Moreover,the key parameters of magnetic fields that regulate intracellular molecular events,including the type,intensity,frequency,duration,and mode of the magnetic field,as well as the precise biological effects of a specific magnetic field on osteoblasts and the underlying mechanisms,have yet to be defined.(6)Further attention needs to be paid to the effects on osteoclasts,nerves,blood vessels,and immune cells in the microenvironment of damaged tissues.Finally,the safety of magnetic materials for human use is yet to be systematically studied in terms of their distribution,metabolism,and acute and chronic toxicities.

Objective:To investigate the effect of insulin-like growth factor 1 (IGF-1) on acute lung injury in septic mice and its underlying molecular mechanism.Methods:Twenty SPF male C57BL/6J mice aged 6-8 weeks were randomly (random number) divided into the sham-operated group, sham-operated + IGF-1 group, sepsis group and sepsis + IGF-1 group, with 5 mice in each group. IGF-1 [60 μg/(kg·d)] was injected via the tail vein for 3 consecutive days in the sham-operated + IGF-1 group and sepsis + IGF-1 group, and mice in the sham-operated group and sepsis group were injected with an equal volume of saline. The tissue of the upper lobe of the right lung was taken to calculate the wet-to-dry ratio, and the upper lobe of the left lung was subjected to HE staining to analyze pathological changes and evaluate lung injury. The levels of interleukin (IL)-6 and IL-1β in the bronchoalveolar lavage fluid (BALF) and serum of mice were detected by ELISA. The expression of p-PI3K, PI3K, p-AKT and AKT in lung tissues was determined via Western blotting. The quantitative data with a normal distribution and homogeneity of variance were compared between the two groups by two independent sample t test. Results:Lung volume was reduced in the sepsis group than in the sham-operated group, obvious surface congestion, dark red color, large bruises and hemorrhagic foci were observed under the pericardium, and the wet-to-dry ratio was significantly elevated ( P<0.05). Compared with the sepsis group, the sepsis + IGF-1 group had slightly increased lung volume, less congestion, darker red color, fewer bruises and hemorrhagic foci, and a lower wet-to-dry ratio ( P<0.05). There was no significant change in lung tissue morphology in the sham-operated + IGF-1 group compared with the sham-operated group. HE staining and lung histopathological scores showed that lung tissue was significantly damaged in the sepsis group than the sham-operated group ( P<0.001), and the pathological score of lung tissue was less damaged in the sepsis + IGF-1 group compared with the sepsis group ( P<0.01). The ELISA results demonstrated that the serum levels of IL-6 and IL-1β were markedly decreased in the sepsis + IGF-1 group than in the sepsis group [(26.22±1.60) pg/mL vs. (45.61±7.85) pg/mL, P<0.05; (87.99±11.80) pg/mL vs. (181.26±10.11) pg/mL, P<0.001]. Moreover, the IL-6 and IL-1β contents in the BALF of the sepsis + IGF-1 group were notably lower than those in the BALF of the sepsis group [(7.67±0.42) pg/mL vs. (20.25±0.43) pg/mL, P<0.001; (17.00±6.08) pg/mL vs. (108.61±5.18), pg/mL P <0.001]. Western blot analysis revealed that the expression of p-PI3K, PI3K, p-AKT and AKT in the lung tissues of mice in the sepsis+IGF-1 group were markedly lower than that in the sepsis group [(0.71±0.05) vs. (1.21±0.09), P<0.05; (0.57±0.08) vs. (1.24±0.22), P<0.01; (0.29±0.07) vs. (1.10±0.04), P<0.001; (0.65±0.17) vs. (1.19±0.07), P<0.01]. Conclusion:IGF-1 ameliorates sepsis-induced acute lung injury in mice, and its protective effect may be achieved by inhibiting the PI3K/AKT pathway.

Objective : To investigate the effects of acarbose and pioglitazone on the levels of sex hormones in adult female rats ，and to explore their regulatory effects on the hypothalamic-pituitary-ovarian axis ( HPOA) and its mechanism． Methods : Adult female SD rats aged 2 months were randomly divided into 0．9% sodium chloride so- lution control group (NS) ，acarbose low (AL) ，medium (AM) and high (AH) dose groups and pioglitazone low (PL) ，medium (PM) and high (PH) dose groups．AL，AM and AH groups were given 20，40 and 60 mg / (kg · d) acarbose，and PL，PM and PH groups were given 5，10 and 15 mg / (kg · d) pioglitazone，respectively．Af- ter 28 days of intervention，serum gonadotropin (FSH，LH) and ovarian secreted hormone ( E2，P，T) were de- tected by ELISA，and the effects of acarbose and pioglitazone on HPOA were investigated by organ index analysis and histopathological observation of pituitary gland and ovary． Results : Compared with the NS group，the serum FSH in the PL，PM and PH groups decreased ( all P＜0. 01) ，the serum LH in the PL，PM and PH groups de- creased (P＜0. 05，P＜0. 01，P ＜0. 01) ，and the organ indices in the PM and PH groups decreased ( all P < 0. 01) ．HE staining of the adenohypophysis in the PL，PM and PH groups showed an increase in eosinophils，a de- crease in basophils，and an expansion and increase in the number of blood sinuses．In the PM and PH groups，HE staining of the ovaries showed that there were no significant differences in follicles at all levels，but the development was poor，the number of primordial follicles decreased，and the number of corpus luteum increased．Compared with the NS group，the serum P in the AM and AH groups decreased ( all P ＜0. 01) ，and serum E2 in AM and AH groups decreasd (all P＜0. 05) ． Conclusion Pioglitazone affects HPOA by regulating pituitary function directly． However，the effect of acarbose on HPOA may be mediated through the gut-brain axis，and has no direct correlation with the ovarian structure．