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.

Objective To construct large medical model named by "Huaxi HongYi"and explore its application effectiveness in assisting medical record generation. Methods By the way of a full-chain medical large model construction paradigm of "data annotation - model training - scenario incubation", through strategies such as multimodal data fusion, domain adaptation training, and localization of hardware adaptation, "Huaxi HongYi" with 72 billion parameters was constructed. Combined with technologies such as speech recognition, knowledge graphs, and reinforcement learning, an application system for assisting in the generation of medical records was developed. Results Taking the assisted generation of discharge records as an example, in the pilot department, after using the application system, the average completion times of writing a medical records shortened (21 min vs. 5 min) with efficiency increased by 3.2 time, the accuracy rate of the model output reached 92.4%. Conclusion It is feasible for medical institutions to build independently controllable medical large models and incubate various applications based on these models, providing a reference pathway for artificial intelligence development in similar institutions.

OBJECTIVE To explore the effect of volatile oil of Ligusticum chuanxiong on the transdermal properties and cytotoxicity of triptolide in vitro. METHODS The chemical constituents of the volatile oil of L. chuanxiong were analyzed by gas chromatography-mass spectrometry. The lower abdominal skin of KM mice was separated and divided into triptolide group， triptolide in compatibility with volatile oil of L. chuanxiong groups at 1∶10， 1∶50， 1∶100 （hereinafter referred to as “compatibility 1∶10”“compatibility 1∶50”“compatibility 1∶100” groups）. After the skin of mice in each group was fully exposed to 0.2 g of the corresponding cream for 24 h， the cumulative transdermal dose （Qn） of triptolide in the receiving solution of each group was determined by high-performance liquid chromatography， and the transdermal absorption rate （Jss） was calculated. Human immortalized keratinocytes （HaCat） were used as a model， the CCK-8 method was used to detect the cell survival rate of different concentrations of the volatile oil of L. chuanxiong and triptolide before and after compatibility. RESULTS A total of 62 chemical constituents of the volatile oil of L. chuanxiong were identified， including Z-ligustilide， senkyunolide， and β-selinene. The Qn （P＜ 0.01） and Jss of triptolide increased within 24 h in the compatibility 1∶10 and 1∶50 groups， while the Qn （P＜0.05） and Jss decreased in the compatibility 1∶100 group as compared with the triptolide group. Compared with the triptolide group， the cell survival rate of HaCat was significantly increased in the compatibility 1∶10 and 1∶50 groups when the triptolide concentrations were 36， 72 and 144 ng/mL （P＜0.05 or P＜0.01）； while the cell survival rate of HaCat was decreased in the compatibility 1∶100 group， but the difference was not statistically significant （P＞0.05）. CONCLUSIONS When the compatibility ratio of triptolide and volatile oil of L. chuanxiong was 1∶10 or 1∶50， it can promote the transdermal absorption of triptolide and reduce the cytotoxicity of triptolide to HaCat.

Lung cancer has the highest incidence and mortality rate among all cancers in China， with its complex and variable nature， long treatment duration， and often poor prognosis. Currently， the treatment of lung cancer mainly employs classical therapies such as surgery， radiotherapy， and chemotherapy， but some patients may experience a series of adverse reactions， which affect their quality of life， survival period， and treatment outcomes. As reported， oxidative stress is one of the important pathogenic factors of lung cancer， affecting its occurrence and development. Oxidative stress is a state of imbalance between oxidative products and antioxidant defense mechanisms in the body. The intervention of oxidative stress in the occurrence and development of lung cancer is related to multiple signaling pathways， including the Kelch-like ECH-associated protein 1 （Keap1）-nuclear factor erythroid 2-related factor 2 （Nrf2） signaling pathway， phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway， mitogen-activated protein kinase （MAPK） signaling pathway， and nuclear factor-κB （NF-κB） signaling pathway. Currently， researchers in China and abroad have conducted extensive studies on the occurrence and development of lung cancer and the pathophysiological mechanisms of drug intervention. The results have shown that oxidative stress plays an important role in the occurrence and development of lung cancer. Chinese medicine monomers and compounds can regulate oxidative stress levels and intervene in related signaling pathways， thereby inhibiting or delaying the occurrence and development of lung cancer. Based on this， this article mainly summarized the relevant signaling pathways regulating oxidative stress intervention in lung cancer in recent years， and also reviewed the latest research on Chinese medicine monomers and compounds in regulating oxidative stress to treat lung cancer， aiming to provide new ideas for research on drug treatment of lung cancer and clinical drug development， as well as to provide references and guidance for further in-depth mechanistic studies in the future.

The identification of clinical questions for clinical practice guidelines of Chinese patent medicine （CPM） is important for subsequent evidence retrieval， evaluation of evidence quality， formation of recommendations. This paper described a methodological proposal for the identification of clinical questions for CPM guidelines to highlight the characteristics of Chinese patent medicine and reflect its effect in specific stage of the disease. Considering four aspects， namely， the drug of Chinese patent medicine （D）， the specific disease stage （S）， comparison （C）， and specific outcome （O）， DSCO framework has been proposed to formulate the clinical questions. Multi-source information through scientific research， policy or standard documents， and clinical data are suggested for collecting clinical questions， and clear selection criteria should be set to finalize the clinical questions to be addressed by the guideline. In addition， the above process needs to be transparently and publicly reported in order to ensure the clarity and completeness of the guidelines.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive dysfunction and behavioral impairment, and there is a lack of effective drugs to treat AD clinically. Existing medications for the treatment of AD, such as Tacrine, Donepezil, Rivastigmine, and Aducanumab, only serve to delay symptoms and but not cure disease. To add insult to injury, these medications are associated with very serious adverse effects. Therefore, it is urgent to explore effective therapeutic drugs for AD. Recently, studies have shown that a variety of enzyme inhibitors, such as cholinesterase inhibitors, monoamine oxidase (MAO)inhibitors, secretase inhibitors, can ameliorate cholinergic system dysfunction, Aβ production and deposition, Tau protein hyperphosphorylation, oxidative stress damage, and the decline of synaptic plasticity, thereby improving AD symptoms and cognitive function. Some plant extracts from natural sources, such as Umbelliferone, Aaptamine, Medha Plus, have the ability to inhibit cholinesterase activity and act to improve learning and cognition. Isochromanone derivatives incorporating the donepezil pharmacophore bind to the catalytic active site (CAS) and peripheral anionic site (PAS) sites of acetylcholinesterase (AChE), which can inhibit AChE activity and ameliorate cholinergic system disorders. A compound called Rosmarinic acid which is found in the Lamiaceae can inhibit monoamine oxidase, increase monoamine levels in the brain, and reduce Aβ deposition. Compounds obtained by hybridization of coumarin derivatives and hydroxypyridinones can inhibit MAO-B activity and attenuate oxidative stress damage. Quinoline derivatives which inhibit the activation of AChE and MAO-B can reduce Aβ burden and promote learning and memory of mice. The compound derived from the combination of propargyl and tacrine retains the inhibitory capacity of tacrine towards cholinesterase, and also inhibits the activity of MAO by binding to the FAD cofactor of monoamine oxidase. A series of hybrids, obtained by an amide linker of chromone in combine with the benzylpiperidine moieties of donepezil, have a favorable safety profile of both cholinesterase and monoamine oxidase inhibitory activity. Single domain antibodies (such as AAV-VHH) targeted the inhibition of BACE1 can reduce Aβ production and deposition as well as the levels of inflammatory cells, which ultimately improve synaptic plasticity. 3-O-trans-p-coumaroyl maslinic acid from the extract of Ligustrum lucidum can specifically inhibit the activity of γ-secretase, thereby rescuing the long-term potentiation and enhancing synaptic plasticity in APP/PS1 mice. Inhibiting γ-secretase activity which leads to the decline of inflammatory factors (such as IFN-γ, IL-8) not only directly improves the pathology of AD, but also reduces Aβ production. Melatonin reduces the transcriptional expression of GSK-3β mRNA, thereby decreasing the levels of GSK-3β and reducing the phosphorylation induced by GSK-3β. Hydrogen sulfide can inhibitGSK-3β activity via sulfhydration of the Cys218 site of GSK-3β, resulting in the suppression of Tau protein hyperphosphorylation, which ameliorate the motor deficits and cognitive impairment in mice with AD. This article reviews enzyme inhibitors and conformational optimization of enzyme inhibitors targeting the regulation of cholinesterase, monoamine oxidase, secretase, and GSK-3β. We are hoping to provide a comprehensive overview of drug development in the enzyme inhibitors, which may be useful in treating AD.

Objective:Based on the benchmarking theory,to elaborate the key issues,paradigm innovations and realization paths of modernized performance management in China's public hospitals,and to provide policy recommendations for the government and hospitals.Methods:Literature/document collection,expert consultation and prototyping were used as methodological support.Results:Hospital performance management lacks management standards,multivariate dynamic indicator systems and realization tools;the digital governance model of"digital technology+management system"has not been established;and horizontal and vertical comparisons among geographic regions,hospitals,departments,and disease types based on standards have not been realized.Innovative paradigms include the establishment of a standard paradigm based on the smallest functional units such as disease types,indexes,bed days,operators,doctors,etc.;the construction of a dynamic index library,the mining of different combinations of indexes and their internal relationships,and the establishment of an evaluation paradigm;the establishment of a longitudinal evaluation of disease types,the evaluation of"specialties,hospitals,and industries",and the positioning of internal functions of hospitals,resource efficiency and the application of healthcare quality evaluation.It creates a multivariate,multidimensional,dynamic evaluation method and visualized evaluation tool and realization path based on big data.Conclusion:It is needed to emancipate the mind to further enhance the cognitive level of digital governance,innovate the paradigm to accelerate the construction of modernized performance management system in public hospitals,and build a platform to promote the application of modernized performance management system in public hospitals.

Objective:Based on the benchmarking theory,to elaborate the key issues,paradigm innovations and realization paths of modernized performance management in China's public hospitals,and to provide policy recommendations for the government and hospitals.Methods:Literature/document collection,expert consultation and prototyping were used as methodological support.Results:Hospital performance management lacks management standards,multivariate dynamic indicator systems and realization tools;the digital governance model of"digital technology+management system"has not been established;and horizontal and vertical comparisons among geographic regions,hospitals,departments,and disease types based on standards have not been realized.Innovative paradigms include the establishment of a standard paradigm based on the smallest functional units such as disease types,indexes,bed days,operators,doctors,etc.;the construction of a dynamic index library,the mining of different combinations of indexes and their internal relationships,and the establishment of an evaluation paradigm;the establishment of a longitudinal evaluation of disease types,the evaluation of"specialties,hospitals,and industries",and the positioning of internal functions of hospitals,resource efficiency and the application of healthcare quality evaluation.It creates a multivariate,multidimensional,dynamic evaluation method and visualized evaluation tool and realization path based on big data.Conclusion:It is needed to emancipate the mind to further enhance the cognitive level of digital governance,innovate the paradigm to accelerate the construction of modernized performance management system in public hospitals,and build a platform to promote the application of modernized performance management system in public hospitals.

Objective:Based on the benchmarking theory,to elaborate the key issues,paradigm innovations and realization paths of modernized performance management in China's public hospitals,and to provide policy recommendations for the government and hospitals.Methods:Literature/document collection,expert consultation and prototyping were used as methodological support.Results:Hospital performance management lacks management standards,multivariate dynamic indicator systems and realization tools;the digital governance model of"digital technology+management system"has not been established;and horizontal and vertical comparisons among geographic regions,hospitals,departments,and disease types based on standards have not been realized.Innovative paradigms include the establishment of a standard paradigm based on the smallest functional units such as disease types,indexes,bed days,operators,doctors,etc.;the construction of a dynamic index library,the mining of different combinations of indexes and their internal relationships,and the establishment of an evaluation paradigm;the establishment of a longitudinal evaluation of disease types,the evaluation of"specialties,hospitals,and industries",and the positioning of internal functions of hospitals,resource efficiency and the application of healthcare quality evaluation.It creates a multivariate,multidimensional,dynamic evaluation method and visualized evaluation tool and realization path based on big data.Conclusion:It is needed to emancipate the mind to further enhance the cognitive level of digital governance,innovate the paradigm to accelerate the construction of modernized performance management system in public hospitals,and build a platform to promote the application of modernized performance management system in public hospitals.

Objective:Based on the benchmarking theory,to elaborate the key issues,paradigm innovations and realization paths of modernized performance management in China's public hospitals,and to provide policy recommendations for the government and hospitals.Methods:Literature/document collection,expert consultation and prototyping were used as methodological support.Results:Hospital performance management lacks management standards,multivariate dynamic indicator systems and realization tools;the digital governance model of"digital technology+management system"has not been established;and horizontal and vertical comparisons among geographic regions,hospitals,departments,and disease types based on standards have not been realized.Innovative paradigms include the establishment of a standard paradigm based on the smallest functional units such as disease types,indexes,bed days,operators,doctors,etc.;the construction of a dynamic index library,the mining of different combinations of indexes and their internal relationships,and the establishment of an evaluation paradigm;the establishment of a longitudinal evaluation of disease types,the evaluation of"specialties,hospitals,and industries",and the positioning of internal functions of hospitals,resource efficiency and the application of healthcare quality evaluation.It creates a multivariate,multidimensional,dynamic evaluation method and visualized evaluation tool and realization path based on big data.Conclusion:It is needed to emancipate the mind to further enhance the cognitive level of digital governance,innovate the paradigm to accelerate the construction of modernized performance management system in public hospitals,and build a platform to promote the application of modernized performance management system in public hospitals.