Nitric oxide synthase(NOS)and its product nitric oxide are involved in learning and memory functions.Increasing evidence shows that NOS plays an important role in the pathogenesis of Alzheimer's disease,influencing β-amyloid protein(Aβ)deposition,neuroinflammation,oxidative stress,abnormal microglia activation,synapse damage,autophagy,abnormal mitochondrial function of nerve cells,and cerebral hypoperfusion or vascular endothelial cell injury.This review summarizes the recent evidence for the role of NOS in the pathogenesis of Alzheimer's disease and provides new feasible targets for the prevention and treatment of Alzheimer's disease.

Nitric oxide synthase(NOS)and its product nitric oxide are involved in learning and memory functions.Increasing evidence shows that NOS plays an important role in the pathogenesis of Alzheimer's disease,influencing β-amyloid protein(Aβ)deposition,neuroinflammation,oxidative stress,abnormal microglia activation,synapse damage,autophagy,abnormal mitochondrial function of nerve cells,and cerebral hypoperfusion or vascular endothelial cell injury.This review summarizes the recent evidence for the role of NOS in the pathogenesis of Alzheimer's disease and provides new feasible targets for the prevention and treatment of Alzheimer's disease.

Objective To explore the application status and development trend of machine learning in the field of pharmacovigilance worldwide,and to provide reference for the research on the application of machine learning in the field of pharmacovigilance.Methods Relevant literature was searched in the Web of Science with the key words of"machine learning"and"pharmacovigilance"from the inception to March 1,2023.R language and other software were used to quantitatively analyze the literature data in this field.The clustering,co-occurrence and emergence visual analysis were carried out on the characteristics of annual published papers,institutions,countries,keywords and other aspects.Results A total of 904 literature were included.The number of literature published showed a fluctuating upward trend since 1994.There was cross-regional,cross-regional and cross-agency cooperation among the cooperative network institutions.The top 5 countries in the number of publications were the United States,China,Japan,South Korea and India,China and the United States had relatively close cooperation in this field.Signal detection,social media and electronic health records were high-frequency keywords in this field.Clustering and association rule analysis showed that this field focused on three aspects signal recognition,unstructured text mining and analysis,and processing and analysis of electronic medical information.At present,machine learning has made significant progress in signal recognition,social media information mining,and unstructured text processing of electronic medical information,which broaden the data sources of pharmacovigilance,improve the real-time monitoring ability of adverse drug reactions,bringing innovation impetus to the field of pharmacovigilance.Conclusion The rapid development of big data and artificial intelligence technologies has led to an increasing integration of machine learning into the field of pharmacovigilance,which promotes technical exchanges and cooperation and cross-disciplinary integration.It is necessary to optimize each machine learning algorithm to improve its accuracy and stability in pharmacovigilance,strengthen the protection measures of data privacy and security to ensure the safety of patient information.Integrating expertise in the fields of science,medicine,and data statistics with a view to promoting technological progress in the field of pharmacovigilance.

Derived from embryonic stem cells, induced pluripotent stem cells, or adult stem cells, liver organoids not only mimic the tissue structure, gene expression patterns, and genetic characteristics of in vivo liver but also demonstrate significant potential in simulating liver diseases, drug screening, precision medicine, and regenerative medicine. This technology is particularly valuable in modeling various conditions such as malignant liver tumors, liver fibrosis, cirrhosis, viral hepatitis, and a range of genetic and metabolic liver diseases. However, challenges remain in enhancing the derivation and proliferation efficiency of organoids, constructing immune microenvironments, developing functional vascular networks, and achieving standardization and automation in the organoid preparation process. Looking forward, with continued technological advancements and innovations, these issues are expected to be resolved, paving the way for liver organoids to play a more substantial role in clinical and research applications, ultimately contributing significantly to public health. This review comprehensively explores the development and extensive applications of liver organoid technology in the field of biomedical science. The aim is to inform subsequent research.

Objective To investigate the potential role of the traditional herbal medicine Datura metel L.in the treatment of psoriasis using TNF-α-induced inflammation in keratinocytes as a model.Methods Keratinocyte cell line HaCaT was used to establish a psoriasis cell model by tumor necrosis factor-alpha(TNF-α)treatment.The ex-periment comprised three groups:a blank control group,TNF-α-induced psoriasis model group,and TNF-α+Datura metel L.intervention group.Level of IL-17 and CCL20 was measured ELISA,expression of nuclear factor kappa B(NF-κB)subunit p65 protein was measured by Western blot.Endothelial cell tube formation experiment was conducted using an in vitro angiogenesis analysis kit.Results Compared to the TNF-α-induced psoriasis model group,the Datura metel L.extract significantly reduced the levels of IL-17 and CCL20 in the cell culture su-pernatant of TNF-α-induced psoriasis model(P＜0.001);Datura metel L.extract markedly decreased the NF-κB subunit p65 protein level in TNF-α-induced psoriasis model cells(P＜0.01);Datura metel L.extract effectively inhibited the induction of endothelial cell tube formation by the cell culture supernatant of the psoria-sis model group.Conclusions The Datura metel L.extract down-regulates NF-κB signaling pathway mole-cules,reducing the production of IL-17 and CCL20 inflammatory factors in inflammatory keratinocytes and in-hibiting angiogenesis.

OBJECTIVE To systematically evaluate the efficacy and safety of transcatheter arterial chemoembolization （TACE） combined with anti-angiogenic drugs for the treatment of unresectable primary liver cancer （PLC）. METHODS Retrieved from Chinese and English databases such as CNKI， the Cochrane Library， Google， and Baidu Academic， randomized controlled trial （RCT） about TACE combined with anti-angiogenic drugs for the treatment of unresectable PLC were collected from the inception to May 27， 2024. After screening the literature， extracting data， and evaluating the quality of the literature， network meta-analysis was performed using R 4.2.2 and Stata 17.0. RESULTS A total of 44 RCT were included， involving 5 607 patients and 8 interventions. The network meta-analysis results showed that for prolonging median overall survival （mOS） and median progression- free survival （mPFS）， TACE+apatinib had the best efficacy， with TACE+apatinib and TACE+sorafenib ranking as the top two. For improving objective response rate （ORR） and disease control rate （DCR）， TACE+donafenib had the best efficacy， with TACE+ donafenib and TACE+ lenvatinib ranking as the top two. In terms of safety， TACE+donafenib was the best， with TACE+donafenib and TACE+apatinib ranking as the top two. CONCLUSIONS TACE+apatinib and TACE+donafenib have good efficacy for patients with unresectable PLC， and TACE+donafenib has the best safety profile.

Objective To explore the current status,research hotspots and development trends of safe medication in the global elderly with multimorbidity,and to provide theoretical reference for research in this field.Methods CNKI,Yiigle and Web of Science were searched for studies on medication safety in the elderly with multimorbidity.The search time was from the establishment of the database to May 1,2024.R language and other software were used to visually analyze the annual number of publications,institutions,and the clustering,refinement,and hotspots and trends of keywords.Results A total of 20 Chinese articles and 654 English articles were included.There is little global attention to this field,and cooperation between institutions needs to be further strengthened.General practice,general practitioners,Beers criteria,polypharmacy,primary care,inappropriate prescribing,medication adherence,deprescribing are the key directions of concern in this field globally.At present,most of the Chinese literature is from the perspective of clinical practice,such as medication management and intervention measures.The English literature mainly focuses on the safety of chronic disease medication,quality of life,medication adherence,and risk of chronic disease medication from the patients'perspective.With the increasing popularity of deprescribing,future research in this area of medication management will place greater emphasis on personalized and precision medicine.Conclusions The study of drug safety in the elderly with multimorbidity needs to establish and improve the primary care mechanism,improve the adherence of patients,and use relevant standards to effectively evaluate the safety and potential risks of polypharmacy in the elderly with multimorbidity,identify potentially inappropriate drugs and deprescribing,to reduce the risk of adverse drug reactions,and to further improve the quality of life and reduce medical costs in the elderly with multimorbidity.

Objective To explore the current status,research hotspots and development trends of safe medication in the global elderly with multimorbidity,and to provide theoretical reference for research in this field.Methods CNKI,Yiigle and Web of Science were searched for studies on medication safety in the elderly with multimorbidity.The search time was from the establishment of the database to May 1,2024.R language and other software were used to visually analyze the annual number of publications,institutions,and the clustering,refinement,and hotspots and trends of keywords.Results A total of 20 Chinese articles and 654 English articles were included.There is little global attention to this field,and cooperation between institutions needs to be further strengthened.General practice,general practitioners,Beers criteria,polypharmacy,primary care,inappropriate prescribing,medication adherence,deprescribing are the key directions of concern in this field globally.At present,most of the Chinese literature is from the perspective of clinical practice,such as medication management and intervention measures.The English literature mainly focuses on the safety of chronic disease medication,quality of life,medication adherence,and risk of chronic disease medication from the patients'perspective.With the increasing popularity of deprescribing,future research in this area of medication management will place greater emphasis on personalized and precision medicine.Conclusions The study of drug safety in the elderly with multimorbidity needs to establish and improve the primary care mechanism,improve the adherence of patients,and use relevant standards to effectively evaluate the safety and potential risks of polypharmacy in the elderly with multimorbidity,identify potentially inappropriate drugs and deprescribing,to reduce the risk of adverse drug reactions,and to further improve the quality of life and reduce medical costs in the elderly with multimorbidity.

A 56-year-old male patient with nasopharyngeal carcinoma had progressed disease after receiving radiotherapy, chemotherapy, and targeted therapy, etc. Then he received chemotherapy combined with immunotherapy (capecitabine and sintilimab). Before receiving the 3rd immunotherapy, no abnormality was found in the relevant examination in the patient. On the 3rd day of treatment, he developed cough, shortness of breath, and other symptoms, and chest CT imaging indicated inflammatory lesion of both lungs. The results of sputum culture, sputum smear examination, G test, GM test, and autoantibody examination were all negative. Infectious pneumonia and interstitial pneumonia with autoimmune features were excluded. The common respiratory adverse reaction to capecitabine was pharyngeal discomfort, and no large-scale pneumonia caused by capecitabine was reported. Therefore, it was considered to be immune-associated pneumonitis cause by sintilimab. Treatments such as intravenous injection of methylprednisolone, IV infusion of cefoperazone sodium and sulbactam sodium and moxifloxacin were given and the patient′s condition was improved. After that, methylprednisolone dose was gradually reduced, and then changed to oral prednisone. On the 10th day of oral prednisone, the symptom of shortness of breath worsened. Chest CT imaging indicated that the pneumonitis was more severe than before. Intravenous methylprednisolone was re-given but the condition was not improved.

A 56-year-old male patient with nasopharyngeal carcinoma had progressed disease after receiving radiotherapy, chemotherapy, and targeted therapy, etc. Then he received chemotherapy combined with immunotherapy (capecitabine and sintilimab). Before receiving the 3rd immunotherapy, no abnormality was found in the relevant examination in the patient. On the 3rd day of treatment, he developed cough, shortness of breath, and other symptoms, and chest CT imaging indicated inflammatory lesion of both lungs. The results of sputum culture, sputum smear examination, G test, GM test, and autoantibody examination were all negative. Infectious pneumonia and interstitial pneumonia with autoimmune features were excluded. The common respiratory adverse reaction to capecitabine was pharyngeal discomfort, and no large-scale pneumonia caused by capecitabine was reported. Therefore, it was considered to be immune-associated pneumonitis cause by sintilimab. Treatments such as intravenous injection of methylprednisolone, IV infusion of cefoperazone sodium and sulbactam sodium and moxifloxacin were given and the patient′s condition was improved. After that, methylprednisolone dose was gradually reduced, and then changed to oral prednisone. On the 10th day of oral prednisone, the symptom of shortness of breath worsened. Chest CT imaging indicated that the pneumonitis was more severe than before. Intravenous methylprednisolone was re-given but the condition was not improved.