BACKGROUND:The local immune microenvironment plays an important regulatory role in the process of bone formation,and the immune system is intricately linked to the skeletal system.OBJECTIVE:To systematically review the promotion of bone regeneration from three aspects:immune cell regulation of microenvironment,regulation of immune response by small extracellular vesicles,and induction of immune response by bone biomaterials,and to elucidate the immune regulatory mechanisms involved in bone regeneration.METHODS:Relevant literature was retrieved from PubMed,CNKI,WanFang Database,and VIP Database,using the search terms of"osteoimmunology,immune microenvironment,small extracellular vesicles,bone regeneration,bone tissue repair,biomaterials,and tissue engineering"in English and Chinese.Repeat and irrelevant literature was screened and removed,and 92 articles that met the criteria were selected for intensive reading and review.RESULTS AND CONCLUSION:Multiple immune cells and bone cells are in the same microenvironment,and immune cells can regulate the differentiation and activity of bone cells,collectively forming an immune microenvironment that affects bone regeneration.Neutrophils can significantly reduce local inflammatory responses in the early stages of bone injury,creating a favorable microenvironment for bone regeneration.M1 macrophages can clear foreign bodies and reduce early inflammatory responses,while M2 macrophages can promote the expression of osteogenic markers and factors,playing an important role in the repair process of bone injury.B cells and T cells can directly or indirectly affect the generation and activity of osteoblasts and osteoclasts,regulate bone metabolism,and promote bone regeneration.Extracellular vesicles of small cells regulate the local immune microenvironment through paracrine secretion,promoting bone formation and angiogenesis at the site of bone injury.The metal ions,surface hydrophilicity,porosity,pore size,surface morphology,and surface roughness on the surface of biomaterials can directly regulate local immune responses,and have anti-inflammatory,angiogenic,and osteogenic effects,thereby accelerating bone regeneration.

BACKGROUND:The local immune microenvironment plays an important regulatory role in the process of bone formation,and the immune system is intricately linked to the skeletal system.OBJECTIVE:To systematically review the promotion of bone regeneration from three aspects:immune cell regulation of microenvironment,regulation of immune response by small extracellular vesicles,and induction of immune response by bone biomaterials,and to elucidate the immune regulatory mechanisms involved in bone regeneration.METHODS:Relevant literature was retrieved from PubMed,CNKI,WanFang Database,and VIP Database,using the search terms of"osteoimmunology,immune microenvironment,small extracellular vesicles,bone regeneration,bone tissue repair,biomaterials,and tissue engineering"in English and Chinese.Repeat and irrelevant literature was screened and removed,and 92 articles that met the criteria were selected for intensive reading and review.RESULTS AND CONCLUSION:Multiple immune cells and bone cells are in the same microenvironment,and immune cells can regulate the differentiation and activity of bone cells,collectively forming an immune microenvironment that affects bone regeneration.Neutrophils can significantly reduce local inflammatory responses in the early stages of bone injury,creating a favorable microenvironment for bone regeneration.M1 macrophages can clear foreign bodies and reduce early inflammatory responses,while M2 macrophages can promote the expression of osteogenic markers and factors,playing an important role in the repair process of bone injury.B cells and T cells can directly or indirectly affect the generation and activity of osteoblasts and osteoclasts,regulate bone metabolism,and promote bone regeneration.Extracellular vesicles of small cells regulate the local immune microenvironment through paracrine secretion,promoting bone formation and angiogenesis at the site of bone injury.The metal ions,surface hydrophilicity,porosity,pore size,surface morphology,and surface roughness on the surface of biomaterials can directly regulate local immune responses,and have anti-inflammatory,angiogenic,and osteogenic effects,thereby accelerating bone regeneration.

Osteoporosis is a common bone metabolic disease， which is mainly characterized by the decrease in the number of bone trabeculae and the destruction of bone tissue microstructure， leading to increased bone fragility and fracture risks. This disease is common in postmenopausal women， elderly men， diabetes patients， and obese people. Due to the lack of awareness to prevent bone losses and the limitations of bone mass measurement methods， osteoporosis is only concerned when there are serious complications， which imposes a heavy burden on both patients and medical resources. Oxidative stress refers to the excessive production of highly active molecules such as reactive oxygen species and reactive nitrogen in the body subjected to harmful stimuli， leading to the imbalance between the oxidative and antioxidant systems and causing oxidative damage. Studies have shown that oxidative stress can increase the generation and activity of osteoclasts and inhibit the differentiation of osteoblasts， thus playing a role in the occurrence and development of osteoporosis. Traditional Chinese medicine （TCM） is considered an effective antioxidant that can alleviate oxidative stress-induced osteoporosis by regulating a variety of signaling pathways. Studies have shown that TCM can alleviate oxidative stress and promote bone angiogenesis and osteogenesis by regulating the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）， nuclear factor-kappa B， and nuclear factor erythroid 2-related factor （Nrf2） signaling pathways. TCM alleviates oxidative stress and promotes osteogenesis by regulating the Nrf2， PI3K/Akt/mammalian target of rapamycin， and secreted glycoprotein Wnt/β-catenin signaling pathways. In addition， TCM regulates NF-κB， mitogen-activated protein kinase， and receptor activator of nuclear factor kappa B （RANK）/RANK ligand/osteoprotegerin signaling pathway to alleviate excessive bone resorption induced by oxidative stress. This paper systematically summarizes the literature on the prevention and treatment of osteoporosis by TCM or its active ingredients via the above-mentioned signaling pathways to reduce oxidative stress in recent years. It briefs the possible molecular mechanisms of oxidative stress regulation-related signaling pathways to cause osteoporosis. In addition， this paper discusses the effects and mechanisms of TCM on bone angiogenesis， osteogenesis， and bone resorption by reducing oxidative stress through the regulation of related signaling pathways， aiming to provide a theoretical basis for the research and clinical treatment of osteoporosis.

BACKGROUND:Gegenmaqi prescription has a good effect on periarthritis of shoulder combined with type 2 diabetes and has a good application prospect,but the specific mechanism is not clear.OBJECTIVE:To explore the action mechanism of Gegenmaqi prescription on periarthritis of shoulder and type 2 diabetes by network pharmacology,molecular docking,and molecular dynamics.METHODS:The active components and protein targets of Gegenmaqi prescription were retrieved from the Traditional Chinese Medicine System Pharmacology database and analysis platform,referred to as TCMSP jointly established by the Shanghai Institute of Materia Medica,Chinese Academy of Sciences and the Institute of Chinese Materia Medica,and China Academy of Chinese Medical Sciences in 2013.Genecards created by Professor Doron Lancet's team at the Weizmann Institute of Science in Israel in 1997,Drugbank created by scientists at the University of Alberta in Canada in 2006,and the OMIM database established by Dr.Victor A.McKusick's team at Johns Hopkins University in the United States in 1966 were used to search the disease protein targets of periarthritis of shoulder and type 2 diabetes,and the intersection targets were obtained based on the WeChat online tool.The protein-protein interaction network was constructed based on the STRING database created in 2000 by Peer Bork's team at the European Bioinformatics Institute(EMBL),and the protein-protein interaction relationship was analyzed.The core targets were screened according to the degree value.The intersection targets were subjected to GO and KEGG enrichment analyses.Finally,molecular docking and molecular dynamics simulation were used to verify the binding of key components to key targets.RESULTS AND CONCLUSION:(1)One hundred and forty-two active ingredients of Gegenmaqi prescription were obtained,including 65 intersections between component targets and disease targets,5 key active ingredients(β-sitosterol,stigmasterol,kaempferol,quercetin,and formononetin),and 5 key targets(AKT1,tumor necrosis factor,interleukin-10,JUN,and TP53).(2)GO function enrichment included 508 items,390 biological process items,77 molecular function items and 41 cell component items.KEGG pathway analysis showed 146 pathways,mainly involving advanced glycation end products receptor signaling pathway,lipid and atherosclerosis signaling pathway,tumor necrosis factor signaling pathway,and interleukin-17 signaling pathway.(3)Molecular docking showed that the key components and key targets had good binding activity.Molecular dynamics simulation showed that β-sitosterol had stable interactions with AKT1,tumor necrosis factor and interleukin 10.(4)Gegenmaqi prescription has been comprehensively studied,and the material basis of its pharmacological effect has been primarily clarified.It is predicted that Gegenmaqi prescription can treat periarthritis of shoulder combined with type 2 diabetes through multi-components,multi-targets,and multi-pathways to exert anti-inflammatory and regulate insulin secretion.

BACKGROUND:Gegenmaqi prescription has a good effect on periarthritis of shoulder combined with type 2 diabetes and has a good application prospect,but the specific mechanism is not clear.OBJECTIVE:To explore the action mechanism of Gegenmaqi prescription on periarthritis of shoulder and type 2 diabetes by network pharmacology,molecular docking,and molecular dynamics.METHODS:The active components and protein targets of Gegenmaqi prescription were retrieved from the Traditional Chinese Medicine System Pharmacology database and analysis platform,referred to as TCMSP jointly established by the Shanghai Institute of Materia Medica,Chinese Academy of Sciences and the Institute of Chinese Materia Medica,and China Academy of Chinese Medical Sciences in 2013.Genecards created by Professor Doron Lancet's team at the Weizmann Institute of Science in Israel in 1997,Drugbank created by scientists at the University of Alberta in Canada in 2006,and the OMIM database established by Dr.Victor A.McKusick's team at Johns Hopkins University in the United States in 1966 were used to search the disease protein targets of periarthritis of shoulder and type 2 diabetes,and the intersection targets were obtained based on the WeChat online tool.The protein-protein interaction network was constructed based on the STRING database created in 2000 by Peer Bork's team at the European Bioinformatics Institute(EMBL),and the protein-protein interaction relationship was analyzed.The core targets were screened according to the degree value.The intersection targets were subjected to GO and KEGG enrichment analyses.Finally,molecular docking and molecular dynamics simulation were used to verify the binding of key components to key targets.RESULTS AND CONCLUSION:(1)One hundred and forty-two active ingredients of Gegenmaqi prescription were obtained,including 65 intersections between component targets and disease targets,5 key active ingredients(β-sitosterol,stigmasterol,kaempferol,quercetin,and formononetin),and 5 key targets(AKT1,tumor necrosis factor,interleukin-10,JUN,and TP53).(2)GO function enrichment included 508 items,390 biological process items,77 molecular function items and 41 cell component items.KEGG pathway analysis showed 146 pathways,mainly involving advanced glycation end products receptor signaling pathway,lipid and atherosclerosis signaling pathway,tumor necrosis factor signaling pathway,and interleukin-17 signaling pathway.(3)Molecular docking showed that the key components and key targets had good binding activity.Molecular dynamics simulation showed that β-sitosterol had stable interactions with AKT1,tumor necrosis factor and interleukin 10.(4)Gegenmaqi prescription has been comprehensively studied,and the material basis of its pharmacological effect has been primarily clarified.It is predicted that Gegenmaqi prescription can treat periarthritis of shoulder combined with type 2 diabetes through multi-components,multi-targets,and multi-pathways to exert anti-inflammatory and regulate insulin secretion.

Talent gather is a process of talent flow and aggregation caused by various factors.Talent gather can not only promote the high-quality development of public hospitals and the aggregation of medical resources but also enhance hospital international competitiveness to form good groups promotion effect.Besides,talent gather can also lead to decrease in management efficiency,an increase in the siphon effect of large hospitals on talents and patients,and existing systems hindering the agglomeration effect.Therefore,it is necessary to strengthen management functions and improve efficiency,to seize the opportunities and breakthroughs in institutional and mechanism reform,and solve the problem of siphoning.Enhance the adaptability of personnel management and promote the advantages of talent aggregation,and establish a talent highland in the field of life and health.

Talent gather is a process of talent flow and aggregation caused by various factors.Talent gather can not only promote the high-quality development of public hospitals and the aggregation of medical resources but also enhance hospital international competitiveness to form good groups promotion effect.Besides,talent gather can also lead to decrease in management efficiency,an increase in the siphon effect of large hospitals on talents and patients,and existing systems hindering the agglomeration effect.Therefore,it is necessary to strengthen management functions and improve efficiency,to seize the opportunities and breakthroughs in institutional and mechanism reform,and solve the problem of siphoning.Enhance the adaptability of personnel management and promote the advantages of talent aggregation,and establish a talent highland in the field of life and health.

Objective To investigate the efficacy of dronedarone combined with low dose metoprol-ol in the treatment of atrial tachycardia.Methods A total of 175 elderly patients with atrial tachy-cardia admitted in Northern Jiangsu People's Hospital during January 2020 to January 2022 were enrolled and then randomly divided into dronedarone group(n=57),metoprolol group(n=55)and combined group(dronedarone+metoprolol,n=48).The frequency,duration and symptom changes of arrhythmia were compared before and after treatment.Results After 3 and 6 months of administration,the total effective rate was significantly higher in the combination group than the dronedarone group and the metoprolol group(P＜0.05).The frequency of atrial fibrillation(AF)attacks[(2.31±1.78)/48 h vs(11.56±18.68)/48 h],AF duration[(4.86±6.73)h/48 h vs(10.92±9.61)h/48 h],atrial flutter(AFL)attacks[(2.33±1.53)/48 h vs(4.33±1.53)/48 h]and AFL duration[(5.15±4.87)h/48 h vs(21.54±20.08)h/48 h]in the combined group,and AFL duration[(2.75±1.94)h/48 h vs(10.29±8.04)h/48 h]in the dronedarone group were reduced after 6 months of treatment(P＜0.05).Conclusion In the treatment of atrial tachycardia,dronedarone combined with low dose metoprolol can not only obviously improve symptoms,but also significantly reduce the atrial premature and atrial tachycardia attacks,decrease the number and duration of AF and AFL attacks,and control heart rate effectively.

Deep brain stimulation(DBS),including optical stimulation and electrical stimulation,has been demonstrated considerable value in exploring pathological brain activity and developing treatments for neural disorders.Advances in DBS microsystems based on implantable microelectrode array(MEA)probes have opened up new opportunities for closed-loop DBS(CL-DBS)in situ.This technology can be used to detect damaged brain circuits and test the therapeutic potential for modulating the output of these circuits in a variety of diseases simultaneously.Despite the success and rapid utilization of MEA probe-based CL-DBS microsystems,key challenges,including excessive wired communication,need to be urgently resolved.In this review,we considered recent advances in MEA probe-based wireless CL-DBS microsystems and outlined the major issues and promising prospects in this field.This technology has the potential to offer novel therapeutic options for psychiatric disorders in the future.

Objective To investigate the clinical application of dabigatran etexilate in elderly patients with non-valvular atrial fibrillation. Methods Clinical materials of elderly non-valvular atrial fibrillation patients with dabigatran etexilate in the Department of Cardiology of the Subei People's Hospital Affiliated to Yangzhou University from January 2021 to June 2022 were collected, and according to the relevant guidelines, clinical application, laboratory indicators and clinical outcomes were statistically analyzed. Results Among 150 patients, 14 cases had no indications for medication and 12 cases had contraindication; 93 cases had insufficient dosage, 9 cases had excessive dosage, 13 cases had unreasonable frequency of administration, and 20 cases had unreasonable conversion with other anticoagulant drugs. Laboratory indicators indicated a significant increase trend in activated partial prothrombin time (APTT) after 1 month, 3 and 6 months of medication (P < 0.05). Clinical outcome showed that the incidence of ischemic stroke events was 3.33%(4/120), the incidence of massive bleeding was 1.67% (2/120), and the incidence of cerebral hemorrhage events was 0.83% (1/120). Conclusion It is common that clinical dosage of dabigatran etexilate in our hospital is insufficient. Pharmacists should pay attention to the standardized application of dabigatran etexilate in elderly patients.