OBJECTIVE To mine the adverse drug events （ADE） signals for gilteritinib， and provide a reference for safe drug use in clinic. METHODS ADE reports with gilteritinib as the primary suspected drug were extracted from the FDA Adverse Event Reporting System （FAERS） database from February 1st， 2018 to December 31st， 2023. Reporting odds ratio （ROR） and proportional reporting ratio （PRR） were applied to detect the risk signals from the data in the FAERS database. The classification and statistics of collected signal data were conducted by using the preferred term （PT） and systemic organ class （SOC） in ADE terminology set of the Medical Dictionary for Regulatory Activities （24.1 edition）. RESULTS Totally， 2 755 gilteritinib-related ADE reports were collected from the database， involving 676 ADE signals （95 positive signals）， 313 PTs and 25 SOCs. Among them， nine signals were not recorded in the package insert. The top 5 PTs consisted of abnormal liver function， decreased platelet count， febrile neutropenia， pneumonia and myelosuppression. The top 6 SOCs for positive signal counts were examinations， general disorders and administration site conditions， respiratory， thoracic and mediastinal disorders， infections and infestations， heart organ disorders， and nervous system disorders. ADEs not recorded in the drug package insert included pneumonia， myelosuppression， decreased blood cell count， sepsis， hemorrhage， infection （not specifically referred to）， septic shock， respiratory failure， and aspergillosis. CONCLUSIONS In addition to paying attention to common ADEs such as liver dysfunction and thrombocytopenia， it is necessary to monitor ADEs with strong signals that are not mentioned in the drug instructions when using gefitinib， such as pneumonia， bone marrow suppression， cytopenia， sepsis， bleeding， infection （not specifically referred to）， septic shock， respiratory failure， Aspergillus infection， elevated serum creatinine and interstitial lung disease.

Keratoconus(KC)is a disease characterized by limited corneal cone-like protrusions accompanied by thinning of the corneal stroma in the area of protrusion, which commonly occurs before and after puberty, manifests itself bilaterally, and is a potentially blinding ophthalmic disease. It is a potentially blinding eye disease. Studies have shown that its pathogenesis is related to environmental factors, inflammatory response, immune function, and mechanical stimulation, but the mechanism of the occurrence and progression of KC has not yet been conclusively determined. A variety of genes, represented by corneal remodeling-related genes, have been found to have some influence on the development of cone cornea. More studies are still digging into the genetic targets associated with the development of cone cornea. This article reviews the targets and influence of genes in the pathogenesis of cone cornea, to explore the application value of genes in the early diagnosis and intervention of cone cornea, and to provide new ideas for future research on the pathogenesis of cone cornea.

OBJECTIVE To investigate the effect of salidroside (Sal) on bone loss in obstructive sleep apnea syndrome(OSAS) rats by regulating the osteoprotegerin(OPG)/receptor activator of nuclear factor kappa-B ligand(RANKL) pathway. METHODS Rats were randomly divided into(12 rats/group) control group,OSAS group,Sal-L,Sal-M,and Sal-H groups(17.5,35,70 mg/kg). Except for the control group,all other groups were used to replicate the OSAS rat model through hypoxia and reoxygenation cycles. Bone density meters,three-point bending experiments,and Micro CT were applied to measure the bone density,biomechanics,and microstructural changes of the femur in rats. ELISA method was applied to detect serum levels of osteocalcin(BGP),alkaline phosphatase(ALP),and cross-linked carboxy-terminal telopeptide of type Ⅰ collagen(CTX-I). RT-PCR was applied to detect OPG and RANKL mRNA levels in the femur. Western blotting was applied to detect the expression of OPG/RANKL pathway proteins in the femur. RESULTS Compared with the control group,the bone density,maximum intensity,maximum load,trabecular bone volume fraction(Tb.BV/TV),trabecular number(Tb.N),trabecular thickness(Tb.Th),BGP,ALP,OPG mRNA and protein expression,OPG/RANKL ratio of rats in the OSAS group were decreased,the mRNA and protein expression of CTX-I and RANKL were increased(P<0.05). Compared with the OSAS group,the bone density,maximum intensity,maximum load,Tb.BV/TV,Tb.N,Tb.Th,BGP,ALP,OPG mRNA and protein expression,OPG/RANKL ratio of rats in the Sal-L,Sal-M,and Sal-H groups were increased sequentially,the mRNA and protein expression of CTX-I and RANKL were decreased sequentially,the above changes were most great in the Sal-H group(P<0.05). CONCLUSION Salidroside promotes bone formation and inhibits bone resorption by increasing OPG expression and decreasing RANKL expression,thereby reducing bone loss in OSAS rats.

ObjectiveTo study the anti-inflammatory effects of Blumea balsamifera （L.） DC oil （BBO） based on nuclear factor kappa-B （NF-κB） nonclassical and arachidonic acid （AA） pathway. MethodsEffects of BBO on the production of slow reacting substance of anaphylaxis （SRS-A） were detected by the ileal smooth muscle method. The contents of prostaglandin E₂ （PGE₂） and leukotriene B₄ （LTB₄） in lipopolysaccharides （LPS） -induced macrophages were detected by ELISA kit. The expression of COX-2， 5-LOX， FLAP and RelB were detected by qRT-PCR. Western blot was performed to detect the effects of BBO on the level of NF-κB nonclassical pathway proteins TNF receptor associated factor 3 （TRAF3）， TNF receptor associated factor 2 （TRAF2）， NF-κB-inducing kinase （NIK）， p100 and RelB. ResultsThe contractile tension of guinea pig ileum was reduced （P<0.001）， and the SRS-A production inhibition rate reached 65.34% at 1mg·mL^-1 BBO concentration. Compared with LPS group， BBO reduced the concentrations of PGE₂ （P<0.05） and LTB₄ （P<0.05）_， and decreased the expressions of COX-2 （P<0.05）， 5-LOX （P<0.05） and FLAP （P<0.05） in AA pathway at concentrations of 40-80 μg·mL^-1. Moreover， 40-80 μg·mL^-1 BBO decreased the concentrations of TRAF3 （P<0.05）， TRAF2 （P<0.05）， and NIK （P<0.05）， and further inhibited the phosphorylation of p100 （P<0.05）， as well as the level of the transcription factor RelB in genes （P<0.05） and proteins （P<0.05） in nonclassical NF-κB pathway， whereas BBO did not cause such changes. ConclusionBBO may potentially exert its anti-inflammatory effects by suppressing the regulatory proteins TRAF3 and TRAF2 and the transcription factor RelB in NF-κB nonclassical pathway. The inhibitory action extending to the induction kinase function of NIK， further hindering the phosphorylation of p100 and its binding with the transcription factor RelB. Consequently， downstream elements in the AA pathway， including the pivotal rate-limiting enzymes COX-2， 5-LOX and FLAP， were altered. This modulation influences the levels of inflammatory mediators such as PGE₂ and LTB₄.

OBJECTIVE To investigate possible electrophysiological mechanisms of psychogenic disorders caused by the classical hallucinogen 2,5-dimethoxy-4-methylamphetamine(DOM).METHODS Microelectrode array implantation in the orbitofrontal cortex(OFC)was performed in adult male SD rats.After one week of recovery from surgery,the drugs were administered intraperitoneally to rats in the following order:DOM(0.5,1.5,and 3.0 mg·kg-1),DOM 3.0 mg·kg-1+ketanserin 1.0 mg·kg-1,DOM 3.0 mg·kg-1+SB242084 3.0 mg·kg-1,ketanserin 1.0 mg·kg-1,SB242084 3.0 mg·kg-1.Saline was given as a control group before each drug treatment.The changes of field potential(LFP)in OFC were recorded by the Plexon in vivo multichannel recording system.There was one week of washout of drugs between medications.RESULTS DOM(0.5,1.5 and 3.0 mg·kg-1)increased the power of high frequency oscillations(HFO,P<0.05)but decreased the power of low γ oscillations(P<0.05,P<0.01)in OFC compared to saline.Ketanserin(1.0 mg·kg-1)antagonized DOM induced changes in low γ oscilla-tions(P<0.01)and HFO(P<0.05)power,but SB242084(3.0 mg·kg-1)did not.CONCLUSION DOM can cause such psychoneurological disorders as hallucinations,which may be related to the power decrease of low γ oscillations and increase of HFO in OFC by acting at 5-HT2A receptors.

Bone organoids can simulate the complex structure and function of the bone tissues, which makes them a frontier technology in organoid researches. Bone organoids show a tremendous potential of applications in bone disease modeling, bone injury repair, and medicine screening. Although advancements have been made so far in constructing bone organoids with functional structures like mineralization, bone marrow, trabecular bone, callus, woven bone, etc, the researches in this field are confronted with numerous challenges such as lack of standardized construction strategies and unified evaluation criteria, which limits their further promotion and application. To standardize researches in bone organoids, the Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, the Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, the Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and the Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine organized related experts to formulate Expert consensus on the construction, evaluation, and application of bone organoids ( version 2024) based on an evidence-based approach. A total of 17 recommendations were put forth, aiming to standardize researches and clinical applications of bone organoids and enhance their value in scientific research and clinical practice.

In order to cultivate qualified oral clinicians, strengthen examination management, and strictly implement process assessment, Special Training Base of Oral and Maxillofacial Radiology in West China Hospital of Stomatology, Sichuan University, has implemented a whole-process and diversified assessment reform. In the part of process assessment, firstly the students were asked to fill in the workload form to give timely feedback on training and truly reflect attendance records; secondly, the performance of trainees in class was comprehensively evaluated in clinical training and theoretical teaching to improve their ability of comprehensive thinking of clinical problems. In the part of result assessment, the traditional theoretical assessment method was weakened, and the ability of comprehensive clinical research was strengthened. Trainees were guided to choose the topic flexibly and use standardized PPT format, and a comprehensive score was determined after assessment. Experts were invited to give their advice, so as to enhance the clinical confidence and scientific research confidence of trainees and help them expand their learning depth and breadth within the limited training time. The analysis of examination methods and assessment results shows that the "whole-process and diversified" assessment mode can truly reflect the training results of trainees and lay a solid foundation for further improvement and implementation of standardized training.

OBJECTIVE To investigate the present equipment and management situation of narcotic drugs in primary healthcare institutions from Qiandongnan prefecture of Guizhou province. METHODS The questionnaire survey was conducted among pharmacy department heads and medical staff from primary healthcare institutions in Qiandongnan prefecture of Guizhou province. Descriptive statistical analysis was conducted on the survey results. RESULTS Of 251 healthcare institutions in this survey， 29 healthcare institutions were equipped with narcotic drugs， accounting for 11.55%. The reasons for the narcotic drugs unequipped were mainly as follows: insufficient attention， no storage conditions for narcotic drugs， complex program of narcotic drug management， small amount usage and so on. Among the 29 primary healthcare institutions equipped with narcotic drugs， all of them did not monitor patient usage， accounting for 100%； 29 healthcare institutions did not implement a return visit or follow-up every 3 months， accounting for 100%. CONCLUSIONS The health administration departments should strengthen the administration of narcotic drugs in primary healthcare institutions. At the same time， training on standardized management and clinical rational application of narcotic drugs for medical staff in primary healthcare institutions should be enhanced by the health administrative department.

As a new type of medical service project, "Internet + nursing service" has become a new trend in the development of nursing. Ningbo area started the exploration of "Internet + nursing service" as early as the end of 2015, and gradually formed the Ningbo model of "government-led, regionalized layout, and online and offline collaborative services, medical professional support, market-based operation". And made the innovative practice of "medical insurance pay at home". By the end of December 2021, there were 6 200 registered nurses on the platform, and a total of 20 993 door-to-door services were provided. 197 medical institutions settled on the platform and carried out 49 home service projects. This paper introduced the exploration experience and practical results of "Internet + nursing service" in Ningbo, and provided reference and reference for the advancement of this work.

OBJECTIVE The 5-HT2A receptor is the major target of classic hallucinogens.Both DOM(2,5-dimethoxy-4-methylamphetamine)and lisuride act at 5-HT2A receptors,and lisuride shares comparable affinity with DOM and acts as a partial agonist at 5-HT2A recep-tors.However,not like DOM,lisuride lacks hallucinogenic properties.Impulsive decision-making refers to the prefer-ence for an immediate small reinforcer(SR)over a delayed large reinforcer(LR).The current study aims to compare the effects of DOM and lisuride on impulsive decision-making and further to investigate the possible receptor mechanisms responsible for the actions of the two drugs.METHODS Impulsive decision-making was evaluated in male Sprague-Dawley rats by the percent-age of choice for the LR in delay discounting task(DDT).Delay to the LR changed in an ascending order(0,4,8,16,and 32 s)across one session.RESULTS DOM(0.3 and 0.5 mg·kg-1)increased impulsive decision-making,and the effects of DOM(0.5 mg·kg-1)was blocked by the 5-HT2A receptor antagonist ketanserin(1.0 mg·kg-1)rather than the 5-HT2C receptor antagonist SB-242084(1.0 mg·kg-1).Contrarily,lisuride(0.1,0.3 and 0.5 mg·kg-1)decreased impulsive decision-making.The effects of lisu-ride(0.3 mg·kg-1)were not antagonized by ketanserin(1.0 mg·kg-1),selective 5-HT1A antagonist WAY-100635(1.0 mg·kg-1)or selective dopamine D4 receptor antagonist L-745870(1.0 mg·kg-1),but were attenuated by the selec-tive dopamine D2/D3 receptor antagonist tiapride(40 mg·kg-1).CONCLUSION DOM and lisuride have contrasting effects on impulsive decision-making via distinct recep-tors.DOM-induced increase of impulsivity is mediated by the 5-HT2A receptor,while lisuride-induced inhibition of impulsivity is regulated by the dopamine D2/D3 receptor.