BACKGROUND:Bone relies on the close connection between blood vessels and bone cells to maintain its integrity.Bones are in a physiologically hypoxic environment.Therefore,the study of angiogenesis and osteogenesis in hypoxic environment is closer to the microenvironment in vivo. OBJECTIVE:To explore the influence of Wenshen Tongluo Zhitong(WSTLZT)formula on H-type bone microvascular endothelial cell/bone marrow mesenchymal stem cell co-culture system in hypoxia environment and its related mechanism. METHODS:Enzyme digestion method and flow sorting technique were used to isolate and identify H-type bone microvascular endothelial cells.Mouse bone marrow mesenchymal stem cells were isolated and obtained by bone marrow adhesion method.H-type bone microvascular endothelial cell/bone marrow mesenchymal stem cell hypoxic co-culture system was established using Transwell chamber and anoxic culture workstation.WSTLZT formula powder was used to intervene in each group at a mass concentration of 50 and 100 μg/mL.The angiogenic function of H-type bone microvascular endothelial cells in the co-culture system was evaluated by scratch migration test and tube formation test.The osteogenic differentiation ability of bone marrow mesenchymal stem cells in the co-cultured system was evaluated by alkaline phosphatase staining and alizarin red staining.The protein and mRNA expression changes of PDGF/PI3K/AKT signal axis related molecules in H-type bone microvascular endothelial cells in the co-cultured system were detected by Western Blotting and q-PCR,respectively. RESULTS AND CONCLUSION:(1)Compared with the normal oxygen group,the scratch mobility and new blood vessel length of H-type bone microvascular endothelial cells were significantly higher(P<0.05);the osteogenic differentiation capacity of bone marrow mesenchymal stem cells was higher(P<0.05);the expression of PDGF/PI3K/AKT axis-related molecular protein and mRNA increased(P<0.05)in the hypoxia group.(2)Compared with the hypoxia group,scratch mobility and new blood vessel length were significantly increased in the H-type bone microvascular endothelial cells(P<0.05);bone marrow mesenchymal stem cells had stronger osteogenic function(P<0.05);the expression of PDGF/PI3K/AKT axis-related molecular proteins and mRNA further increased(P<0.05)after treatment with different dose concentrations of WSTLZT formula.These findings conclude that H-type angiogenesis and osteogenesis under hypoxia may be related to the PDGF/PI3K/AKT signaling axis,and WSTLZT formula may promote H-type vasculo-dependent bone formation by activating the PDGF/PI3K/AKT signaling axis,thereby preventing and treating osteoporosis.

In order to understand the prevalence and antimicrobial resistance of Enterococcus faeca-lis(E.faecalis)and Enterococcus faecium(E.faecium)isolated from human,pig and environ-ment in a Xinjiang pig farm,and to investigate the prevalence and potential harm of antimicrobial resistance genes,858 fecal samples from pig farm workers,anal swabs from pig and environment were collected for isolation,identification,antimicrobial susceptibility test and drug resistance gene detection.The results showed that 429 strains of E.faecalis and 222 strains of E.faecium were i-solated.The distribution of Enterococcus species varied among different sources.The isolation rate of E.faecalis was higher in pig anal swabs(73.1％,309/423)and human fecal samples(68.4％,26/38).E.faecium(42.3％,168/397)was mainly isolated from environmental samples.The drug resistance of E.faecalis and E.faecium isolated from pigs was similar to that of E.faecium isola-ted from environment.The drug resistance rates of E.faecalis and E.faecium isolated from pigs were more serious than those from humans to tetracycline,doxycycline,florfenicol and erythromy-cin,and they were more sensitive to ciprofloxacin and levofloxacin.More than 30.0％of E.faecalis and E.faecium isolated from pigs and environment were intermediate to linezolid.E.faecalis from three sources and E.faecium from environmental sources were mainly resistant to five drugs,while E.faecium from pigs was mainly resistant to six drugs.The detection rates of tet(M)and tet(L)genes in E.faecalis and E.faecium isolates from human,animal and environmental sources were more than 70.0％,which was consistent with the results of drug sensitivity.In addition,the cfr,optrA and poxtA genes that mediate oxazolidinone resistance were detected to varying extent.The cfr gene was only detected in four E.faecalis isolates from swine,one E.faecalis isolate from environment and two E.faecium isolates from environment.The positive rate of optrA gene in E.faecium isolated from pigs and environment was higher than that from humans,and the posi-tive rate was more than 60.0％.The positive rate of poxtA gene in E.faecium isolated from pigs and humans was more than 45.0％.The similar drug resistance situation suggests that there is the phenomenon of mutual contamination of drug-resistant bacteria in human-animal-environment.Therefore,we should consider from the perspective of one health,formulate comprehensive disin-fection and control programs,block the transmission route of drug-resistant strains and drug re-sistance genes between human-animal-environment,standardize the use of antibiotics,and reduce the enrichment of antibiotics in human-animal-environment,so as to reduce the risk of drug-resist-ant bacteria.

Objective:The outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for myelodysplastic syndromes-evolved acute myeloid leukemia (MDS-AML) were explored.Methods:A retrospective review was conducted for 54 patients with MDS-AML treated with allo-HSCT in the Institute of Hematology and Blood Disease Hospital from January 2018 to August 2022. The clinical effects after transplantation were observed, and the related risk factors influencing prognosis were explored.Results:Of the total 54 patients, 26 males, 28 females, and 53 patients achieved hematopoietic reconstruction. After a median follow-up of 597 (15-1 934) days, the 1 year overall survival (OS) rate, disease-free survival (DFS) rate, relapse rate (CIR) and non-relapse mortality (NRM) rate were 75.8%±5.8%, 72.1%±6.1%, 12.7%±4.9%, and 17.1%±5.2%, respectively. The 3 year estimated OS, DFS, CIR, and NRM rates were 57.8%±7.5%, 58.1%±7.2%, 23.2%±6.6%, and 23.7%±6.6%, respectively. The cumulative incidence of acute graft-versus-host disease (aGVHD) was 57.5%±6.9%, and the cumulative incidence of chronic graft-versus-host disease (cGVHD) was 48.4%±7.7%. Hematopoietic cell transplantation comorbidity index (HCT-CI) before transplantation was ≥2, minimal residual disease (MRD) was positive on the day of reconstitution, grade Ⅲ/Ⅳ aGVHD, bacterial or fungal infection and no cGVHD after transplantation were adverse prognostic factors for OS ( P<0.05). COX regression model for multivariate analysis showed that HCT-CI score before transplantation, bone marrow MRD on the day of response, grade Ⅲ or Ⅳ aGVHD, and cGVHD after transplantation were the independent adverse factors for OS ( P=0.001, HR=6.981, 95% CI 2.186-22.300; P=0.010, HR=6.719, 95% CI 1.572-28.711; P=0.026, HR=3.386, 95% CI 1.158-9.901; P=0.006, HR=0.151, 95% CI 0.039-0.581) . Conclusion:For patients with MDS-AML and high risk of relapse, allogeneic transplantation must be considered as soon as possible. The enhanced management of post-transplantation complications and maintenance treatment should be provided whenever possible after transplantation.

Objective:To establish a medical equipment maintenance model based on the analytic hierarchy process(AHP),and to study its application effect in the management of orthopedic medical equipment in hospitals.Methods:Based on the analytic hierarchy process(AHP),the equipment maintenance model was constructed from the classification of the service life,failure mode,failure consequences and other indicators of orthopedic medical equipment.25 sets of medical equipment in clinical use in the Department of Orthopedics of The Second Affiliated Hospital of the Air Force Medical University from 2019 to 2022 were randomly selected,taking the time as the dividing point,the traditional orthopedic medical equipment management model(referred to as traditional management)was implemented during the equipment use period from 2019 to 2020,and the equipment maintenance model based on AHP was used to manage orthopedic medical equipment(referred to as model management)during the equipment use period from 2021 to 2022.A total of 1,000 equipment usage records were collected,500 for each mode,and the effect of equipment repair and maintenance,the satisfaction score of equipment usage management and the incidence of adverse events were compared under different management modes.Results:The cost-effectiveness of equipment using the model management mode was an average of CNY(34,500.00±4,700.00)per unit per year,which was higher than that of the traditional management mode,the difference was statistically significant(t=8.417,P<0.05),the maintenance costs and operating costs were CNY(15,381.95±13.67)per year and CNY(31,600.00±10,500.00)per year,respectively,which lower than those of the traditional management model,the difference was statistically significant(t=858.675,5.371,P<0.05).The scores of equipment management personnel on equipment performance,timeliness and cleanliness of the equipment using the model management mode,and the patients'satisfaction with convenience,effect and comfort of the equipment(9.65±1.14),(9.74±1.38),(9.53±1.09),(9.58±1.07),(9.62±1.14)and(9.81±1.28),respectively,which were all higher than those of the traditional management mode,the difference was statistically significant(t=5.629,5.687,4.736,8.085,5.330,7.680,P<0.05).The total incidence of adverse events in equipment using model management mode was 4.8%(24/500),which was lower than that of the traditional management mode,the difference was statistically significant(x2=12.515,P<0.05).Conclusion:The application of medical equipment maintenance model based on analytic hierarchy process to the management of orthopedic medical equipment can effectively reduce the equipment maintenance cost,improve the cost-effectiveness of the equipment,and improve the satisfaction of the equipment use management personnel.

Objective To investigate the effects of nuclear respiratory factor 1(NRF1)on mitochondrial and cog-nitive dysfunction in Alzheimer's disease(AD)model mice.Methods The 5 × FAD mice were utilized as a mod-el for Alzheimer's disease,and the sparsely labeled AAV virus overexpressing NRF1(AAV-NRF1)was adminis-tered via stereotaxic injection into the brain.The expression of NRF1 in hippocampus was determined by Western blot,the morphology of mitochondria in hippocampus was observed by transmission electron microscope,the den-dritic spines of sparsely labeled neurons in the CA1 region were visualized and quantified using confocal laser mi-croscopy,cognitive and memory functions of mice were evaluated using the Morris water maze test,while electro-physiological methods were employed to detect long-term potentiation(LTP)of synaptic efficacy.Results The ex-pression of NRF1 in the hippocampus was significantly upregulated following stereotactic injection of AAV-NRF1(P＜0.001).This intervention led to notable improvements in mitochondrial morphology within hippocampal neurons,as well as enhanced cognitive and memory functions in mice(P＜0.01).Moreover,there was a significant in-crease in dendritic spine density among neurons located in the CA1 region of the hippocampus(P＜0.001),ac-companied by long-lasting and stable long-term potentiation(LTP)and a substantial elevation in fEPSP slope(P＜0.01).Conclusion The overexpression of NRF1 in a 5 × FAD mouse model of Alzheimer's disease(AD)initia-ted the restoration of mitochondrial dysfunction and enhanced synaptic plasticity,indicating that these alterations may contribute to the therapeutic efficacy of NRF1 overexpression in ameliorating cognitive dysfunction associated with AD.

Objective:To investigate long-term auditory changes and characteristics of Alport syndrome（AS） patients with different degrees of renal injury. Methods:Retrospectively analyzing clinical data of patients diagnosed AS from January 2007 to September 2022, including renal pathology, genetic detection and hearing examination. A long-term follow-up focusing on hearing and renal function was conducted. Results:This study included 70 AS patients, of which 33（25 males, 8 females, aged 3.4-27.8 years） were followed up, resulting in a loss rate of 52.9%.The follow-up period ranged from 1.1to 15.8 years, with 16 patients followed-up for over 10 years. During the follow-up, 10 patients presenting with hearing abnormalities at the time of diagnosis of AS had progressive hearing loss, and 3 patients with new hearing abnormalities were followed up, which appeared at 5-6 years of disease course. All of which were sensorineural deafness. While only 3 patients with hearing abnormalities among 13 patients received hearing aid intervention. Of these patients,7 developed end-stage renal disease（ESRD）, predominantly males （6/7）. The rate of long-term hearing loss was significantly different between ESRD group and non-ESRD group（P=0.013）. There was no correlation between the progression of renal disease and long-term hearing level（P>0.05）. kidney biopsies from 28 patients revealed varying degrees of podocyte lesion and uneven thickness of basement membrane. The severity of podocyte lesion was correlated with the rate of long-term hearing loss（P=0.048）, and there was no correlation with the severity of hearing loss（P>0.05）. Among 11 cases, theCOL4A5mutationwas most common （8 out of 11）, but there was no significant correlation between the mutation type and hearing phenotype（P>0.05）. Conclusion:AS patients exhibit progressive hearing loss with significant heterogeneity over the long-term.. THearing loss is more likely to occur 5-6 years into the disease course. Hearing abnormalities are closely related to renal disease status, kidney tissue pathology, and gene mutations, emphasizing the need for vigilant long-term hearing follow-up and early intervention.
Male ; Child ; Female ; Humans ; Nephritis, Hereditary/pathology* ; Retrospective Studies ; Kidney ; Deafness ; Hearing Loss/genetics* ; Kidney Failure, Chronic/pathology* ; Mutation

Objective To investigate the imaging features of papillary tumor of the pineal region(PTPR).Methods The ima-ging data of 10 patients with PTPR confirmed by operation and pathology were analyzed retrospectively.Results All lesions were located in the posterior commissure area of the posterior inferior wall of the third ventricle.All lesions were heterogeneously hyper-intensity on T1WI and hyperintensity on T2WI.Multiple small cysts or microcapsules signal intensity were observed within the tumor.Of all 10 lesions,there were 9 lesions with high signal intensity within or at the edge of the lesion on T1WI.All lesions showed restricted diffusion.All 10 cases showed uneven and obvious enhancement patterns.Midbrain tectum was compressed and moved backward in 5 cases,moved downward in 2 cases,moved forward and downward in 1 case,and was not clearly displayed in other 2 cases.One case was disseminated and 1 case was hyperperfusion.There were all 10 cases with obstructive hydrocephalus and equal or slightly high density on CT imaging,and 4 cases with calcification.Conclusion Imaging characteristics of PTPR included the lesions centered on the posterior commissure,compressed tectum with backward and downward,multiple small cysts or micro-capsules components within the tumor,hyperintensity on T1WI,and uneven and obvious enhancement patterns.

Objective To strengthen nursing awareness and attention,and improve the quality of medication and nursing care,Meta-analysis was used to evaluate the occurrence of sodium-glucose transporter 2 inhibitor related ketoacidosis.Methods Relevant randomized controlled trials were searched in 6 databases,such as CNKI,PubMed,Embase,and the Clinical trial platform,and the literature was screened based on inclusion and exclusion criteria.The search time was from the establishment of databases to January 2023.Revman 5.4.1 was used for quality evaluation and Meta-analysis.Results 24 randomized controlled trials were included.The Meta-analysis results showed that sodium-glucose transporter 2 inhibitors increased the incidence of ketoacidosis(RR=2.52,95％CI[1.82,3.49],P＜0.001).Subgroup analysis showed that the sodium-glucose transporter 2 inhibitors increased the incidence of ketoacidosis in patients with type 2 diabetes(RR=2.42,95％CI[1.70,3.43],P＜0.001),cardiovascular disease(RR=2.32,95％CI[1.59,3.39],P＜0.001),and chronic kidney disease(RR=2.82,95％CI[1.73,4.58],P＜0.001).Cargliflozin(RR=3.21,95％CI[1.43,7.18],P=0.005),Daggliflozin(RR=2.73,95％CI[1.51,4.93],P＜0.001),and Sogliflozin(RR=1.92,95％CI[1.06,3.50],P=0.030)increased the incidence of ketoacidosis,while Engliflozin(RR=1.80,95％CI[0.79,4.11],P=0.160)did not have a significant effect.When the eGFR of patients≤60(mUmin/1.73m2)(RR=2.74,95％CI[1.63,4.60],P＜0.001),the duration of medication≤ 12 month(RR=3.31,95％CI[1.79,6.12],P＜0.001),or the duration of medication＞12 month(RR=2.19,95％CI[1.23,3.91],P=0.008),the sodium-glucose transporter 2 inhibitors increased the occurrence of ketoacidosis.Conclusion For patients receiving sodium-glucose transporter 2 inhibitors treatment regardless of whether they are complicated with diabetes,especially those with heart and kidney diseases,in the early and middle stages of medication,with eGFR ≤60 ml/(min·1.73m2),and those with other susceptibility factors,we should strengthen the observation of patients'medication,optimize medication care,and early identify and intervene in the occurrence of ketoacidosis.

OBJECTIVE To analyze the factors affecting the inclusion of Chinese patent medicines in China’s National reimbursement drug list （NRDL）， and assist these medicines in fully reflecting their actual value in the reimbursement admission process. METHODS From the official website of the China’s National Healthcare Security Administration， the application materials of Chinese patent medicines outside the list that passed the formal review from 2021 to 2023 were obtained， including basic information on the medicines， safety， efficacy， innovation and heritage information， and supplemented with references from the pharmacopeia and the Yaozhi Database. Economic information and enterprise information were obtained through websites such as the Yaozhi Database. Univariate analysis， multivariate Logistic regression analysis and stepwise regression analysis were conducted on the initial application information and admission outcomes of the medicines. Sensitivity analysis was also performed on medicines that applied multiple times in different years as independent samples. RESULTS & CONCLUSIONS There were 27 Chinese patent medicines that passed the formal review from 2021 to 2023， involving 37 applications. The univariate analysis results showed that medicines with descriptions of traditional Chinese medicine （TCM） syndrome types， clear adjustment information for medication plans for specific population groups， short time to market in the indications of the package insert， registered as Class 1 to 6 following or class Ⅰ innovative TCM/class Ⅲ ancient classic prescription compound TCM registered， and those produced by enterprises listed in the “Top 100 Chinese Pharmaceutical Industry Enterprises” list for the current year were more likely to be included in the NRDL （P＜0.05）. The results of the multivariate Logistic regression analysis were not statistically significant， but the stepwise regression results indicated good consistency with the univariate analysis. The results of the sensitivity analysis were consistent with the trend of basic analysis. It is recommended that Chinese patent medicine enterprises further clarify the description of product instructions， expand innovation capabilities， inherit and develop ancient classic prescriptions， and promptly complete clinical trial evidence.

Objective:This study aimed to compare the audiological characteristics between children with unilateral auditory neuropathy (UAN) and single-sided deafness (SSD) to establish a valid basis for the differential diagnosis of children with UAN.Methods:A retrospective analysis was conducted on audiological and imaging evaluations of children with UAN and SSD who were treated at Beijing Children′s Hospital of Capital Medical University between May 2015 and June 2023. There were 17 children with UAN, comprising 10 males and 7 females, with an average age of 4.7 years. Additionally, there were 43 children with SSD, consisting of 27 males and 16 females, with an average age of 6.5 years. Audiological assessments included Auditory brainstem response (ABR), Steady-state auditory evoked potential (ASSR), Behavioural audiometry, Cochlear microphonic potential (CM), Distortino-product otoacoustic emission (DPOAE), and acoustic immittance test. The results of the audiological assessment and imaging phenotypic between the two groups of children were compared and analyzed by applying SPSS 27.0 statistical software.Results:(1) The UAN group (77.8%) had a significantly higher rate of ABR wave III L than the SSD group (20.9%) ( P<0.01). The PA thresholds at 500 Hz and 1 000 Hz of children with SSD were higher than those of children with UAN, while the ASSR thresholds at 500 Hz, 1000 Hz, 2 000 Hz, and 4 000 Hz of children with SSD were significantly higher than those of children with UAN ( P<0.05). (2) The degree of hearing loss in both UAN and SSD children was predominantly complete hearing loss. The percentage of complete hearing loss was significantly higher (χ2=4.353, P=0.037) in the SSD group (93.0%, 40/43) than in the UAN group (63.6%, 7/11). However, the percentage of profound hearing loss was significantly higher in the UAN group (27.3%, 3/11) than in the SSD group (2.3%, 1/43) ( Fisher′s exact test, P=0.023). In terms of hearing curve configuration, the percentage of flat type was significantly higher in the SSD group (76.7%, 33/43) than in the UAN group (36.4%, 4/11). The proportion of the UAN group (27.3%, 3/11) was significantly higher than that in the SSD group (2.3%, 1/43) in ascending type ( P<0.05). There were no statistically significant differences in the hearing curves of the declining type and other types between the two groups ( P>0.05). (3) The proportion of imaging assessment without abnormality was significantly more common in the UAN group (81.8%) than in the SSD group (37.1%) (χ2=6.695, P=0.015). Conclusions:Compared to children with SSD, the occurrence of wave III L on the ABR test was significantly more common in children with UAN. The percentage of ascending hearing curves was significantly higher in children with UAN than in children with SSD. ASSR thresholds were significantly lower in children with UAN. The normal imaging phenotype was significantly more common in children with UAN than in children with SSD.