Objective To explore the effects of CDP-diacylglycerol synthase 1(CDS1)on autophagy and amyloid deposition in hippocampal neurons of mice and the related mechanism.Methods Congo red and immunohistochemical staining were used to observe the amyloid deposition in hippocampus of amyloid precursor protein(APP)/presenilin 1(PS1)double-transgenic mice.Lentivirus-mediated overexpression of APP was induced in HT22 cells,and Congo red staining was used to observe the amyloid deposition in HT22 cells.The protein expression levels of microtubule-associated protein 1 light chain 3(LC3)-Ⅱ and P62 in the hippocampus of APP/PS1 double-transgenic mice and APP-overexpressed HT22 cells were detected by Western blotting.The differential protein CDS1 was screened based on the hippocampal proteomics results of APP/PS1 double-transgenic mice.The expression of CDS1 protein in hippocampal tissue of APP/PS1 transgenic mice and APP-overexpressed HT22 cells was detected by Western blotting.After lentivirus-mediated APP overexpression in HT22 cells,CDS1 was overexpressed,and the protein expression levels of LC3-Ⅱ and P62 were detected by Western blotting.Results β-amyloid protein(Aβ)was deposited in the hippocampus of APP/PS1 mice and in HT22 cells overexpressing APP.The levels of LC3-Ⅱ and P62 protein in the hippocampus of APP/PS1 double-transgenic mice and APP-overexpressed HT22 cells were significantly increased.A differential metabolic pathway,glycerophospholipid metabolic pathway,was screened by Kyoto Encyclopedia of Genes and Genomes pathway analysis in the proteomic results of APP/PS1 double-transgenic mice,and the differential protein CDS1 was obtained.Compared with wild-type C57BL/6 mice,APP/PS1 double-transgenic mice exhibited a significantly decrease in CDS1 protein expression in the hippocampus(0.46±0.07 vs 1.00±0.25,P＜0.01).Similarly,lentivirus-mediated overexpression of APP in HT22 cells resulted in decreased CDS1 protein levels compared to cells infected with empty viral vector controls(0.68±0.18 vs 1.00±0.13,P＜0.01).The autophagy flow of nerve cells was significantly restored after the CDS1 overexpression in APP-overexpressed HT22 cells(LC3-Ⅱ:1.00±0.15 vs 0.21±0.05,P＜0.01;P62:1.00±0.16 vs 0.67±0.10,P＜0.01),and Aβ deposition was significantly decreased.Conclusion Downregulation of CDS1 expression can induce dysfusion of autophagosome and lysosome,promoting amyloid deposition in hippocampus of mice with Alzheimer's disease.

Alzheimer's disease(AD)is a progressive neurodegenerative disease with hidden onset.Recent researches have shown that apolipoprotein E4(APOE4)is a high-risk genetic factor of AD,and the clinical symptoms in APOE4 genotype AD patients are closely related to metabolic disorders.This paper reviewed the role of APOE4 in the pathogenesis of AD,and it is indicated that APOE4 contributes to the injury of the cerebral blood-brain barrier,is associated with the disorder of cerebral glucose and lipid metabolism,and leads to the damage of the scavenging ability of microglia.Moreover,this paper explored the approach of early intervention of AD with traditional Chinese medicine(TCM)based on the APOE4 pathogenesis.Based on the pathogenesis of AD being deficiency in origin and excess in superficiality,and under the guidance of the principle of prevention before illness in TCM,it is proposed that early TCM intervention for APOE4 genotype AD patients with metabolic disorders can be performed through improving the phlegm-dampness constitution,by focusing on insulin resistance-related indicators,and with traditional Chinese drug therapy based on syndrome differentiation alone or together with comprehensive management of exercises,diet control and drug interventions,thus to reduce or delay the onset of APOE4 genotype AD.

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.

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.

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.

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.

【Objective】 To explore the relevant risk factors of Henoch-Schonlein purpura (HSP) recurrence so as to provide some theoretical basis for early identification of children prone to recurrence. 【Methods】 The clinical data of 417 children with HSP hospitalized in Department of Pediatrics, The First Affiliated Hospital of Xi’an Jiaotong University, in the past five years were collected and followed up. They were divided into recurrent group and non-recurrent group. Cox regression analysis was used for univariate and multivariate analysis, and finally the independent risk factors for HSP recurrence were screened. 【Results】 A total of 417 children with initial onset of HSP were included in the study. During the follow-up period of 14 to 60 months, 78 cases recurred, and the recurrence rate was 18.7%. 94.9% of the children had relapse within 1 year. The results of univariate Cox regression analysis showed that age >7 years old at the time of onset, history of infection, history of strenuous exercise, duration of rashes more than 4 weeks, high level of neutrophil-to-lymphocyte ratio (NLR), and high level of platelet-to-lymphocyte ratio (PLR) were all risk factors for HSP recurrence (P<0.05). The prolongation of activated partial thromboplastin time (APTT) was the protective factor for HSP recurrence (P<0.05). Multivariate Cox regression analysis showed that age >7 years old at the time of onset, history of infection, history of strenuous exercise, duration of rashes for more than 4 weeks at the first onset, and high PLR level were independent risk factors for HSP recurrence (P<0.05). 【Conclusion】 The recurrence rate of HSP was 18.7%, and 94.9% of the recurrent children had HSP recurrence within 1 year. Therefore, children with HSP should be followed up for at least one year. For children aged > 7 years at the time of onset, with a history of infection, vigorous exercise, rashes lasting more than 4 weeks, and high PLR level, nursing should be strengthened after discharge to avoid infection and vigorous exercise and increase the frequency of follow-up.