Natural products are important sources for the discovery of anti-tumor drugs. Evodiamine is the main alkaloid component of the traditional Chinese herb Wu-Chu-Yu, and it has weak antitumor activity. In recent years, a number of highly active antitumor candidates have been discovered with a significant progress. This article reviews the research progress of evodiamine-based antitumor drug design strategies, in order to provide reference for the development of new drugs with natural products as leads.

In this study, fluvoxamine maleate sustained-release pellet system tablets were prepared and were used to evaluate their release behaviors in vitro. Fluvoxamine maleate pellets were prepared using centrifugal-spherization method and coated by fluidized bed as bottom-spray. The multi-unit sustained-release pellets and appropriate excipients for prescription volumes were mixed uniformly and then compressed to tablets. Screening and determining the optimal formulation of drug loaded pellets through L8 (2⁴) Taguchi experiment. Using Minitab software to design a DOE experiment with 2⁴ partial factors, including material temperature, fan speed, atomization pressure, and spray rate to optimize the bottom spray coating process. Taking monostearate glycerol ester with a particle size of 24-40 mesh as the main diluent for tableting to relieve the delamination phenomenon between pellets and excipients during tablet pressing and reduce mechanical damage to the coating film. By examining the powder fluidity indexes such as angle of repose, bulk density, tapped density, and Hausner ratio of mixed particles, it was found that the flowability and compressibility are good and suitable for direct compression. Evaluate the basic properties of the sustained-release tablets, investigate the in vitro release behavior and study the release mechanism. The results of in vitro release test showed that the self-made sustained-release tablets could disintegrate into independent pellet units in phosphate buffer at pH 6.8 and release slowly within 24 h, which conformed to the first-order drug release model. The fluvoxamine maleate sustained-release pellet system tablets meet the requirements of preparation design and has a great commercial prospect.

Objective This study aims to investigate the current status of burnout among anesthesi-ology residents,and to explore its influencing factors and potential interventions.Methods A total of 2 651 practicing anesthesiology residents from 218 hospitals nationwide were included in this study.Demographic characteristics,occupational features,and psychological resilience scores(Connor-Davidson resilience scale)were collected using a questionnaire distributed electronically.The Maslach burnout inventory-human service survey(MBI-HSS)was used to assess burnout.A comparison between groups with and without occu-pational burnout was conducted.Multiple logistic regression analysis was used to identify risk factors for burnout among anesthesiology residents.Results Out of the expected 2 651 questionnaires,1 990 valid responses were received(response rate 77.7%).The prevalence of burnout among the residents was 53.4%(1 063/1 990).Compared with residents without occupational burnout,those with burnout had a signifi-cantly higher proportion of females,working in tertiary hospitals,unmarried individuals,frequency of en-countering challenging patients,participating in on-call duty,and research tasks,and had a significantly lon-ger weekly working hours(P＜0.05).Multivariate logistic regression analysis indicated that female(OR = 1.58,95%CI 1.28-1.97,P＜0.01),longer working hours(OR = 1.62,95%CI 1.45-1.81,P＜0.01),and higher frequency of encountering challenging patients(OR = 1.11,95%CI 1.11-1.40,P＜0.01)were risk factors for occupational burnout.High levels of psychological resilience was protective factor against burnout(OR = 0.86,95%CI 0.84-0.88,P＜0.01).Conclusion The occurrence of burnout among anesthesiology residents is high.It is crucial to focus on and design practical preventive measures to en-hance psychological resilience,ensuring healthy physical and mental development of the resident community.

Tezepelumab(AMG 157/MEDI9929)is a human monoclonal antibody against the epithelial cell-derived cytokine thymic stromal lymphopoietin(TSLP).It is primarily used to treat moderate to severe asthma,particularly in patients with a non-eosinophilic inflammatory phenotype,whose asthma remains uncontrolled despite the use of long-acting beta-agonists and moderate to high doses of inhaled glucocorticoids.This article will summarise the mechanism of action,clinical trial efficacy and safety and tolerability of Tezepelumab in order to provide a comprehensive understanding of the drug and inform clinical work.

Objective:To develop an Arteriovenous Fistula Physical Examination Knowledge, Attitude, and Practice Scale for Hemodialysis Nurses and test its reliability and validity.Methods:Based on the theory of knowledge, attitude, and practice, a preliminary scale draft was formed through a literature review, three rounds of Delphi expert consultation, and a pre-survey. Using convenience sampling, 311 hemodialysis nurses were selected for a survey from December 2022 to February 2023 for item analysis, exploratory factor analysis and reliability testing. Another survey was conducted on 260 hemodialysis nurses from February to June 2023 for confirmatory factor analysis, convergent validity, and discriminant validity testing.Results:The Arteriovenous Fistula Physical Examination Knowledge, Attitude, and Practice Scale for Hemodialysis Nurses included three subscales and five dimensions, with a total of 33 items. The content validity index at the item level was 0.867 to 1.000, and the content validity index at the scale level was 0.992. After exploratory factor analysis, two, one, and two common factors were extracted from the knowledge, attitude, and practice subscales, with cumulative variance contribution rates of 70.114%, 75.192%, and 67.467%, respectively.Confirmatory:factor analysis showed that the model fitted well. The Cronbach's α coefficients of the three subscales were 0.929 to 0.943, the half reliability coefficients were 0.861 to 0.903, and the retest reliability coefficients were 0.824 to 0.874. Conclusions The Arteriovenous Fistula Physical Examination Knowledge, Attitude, and Practice Scale for Hemodialysis Nurses has good reliability and validity and can be used to evaluate the physical examination ability of hemodialysis nurses for arteriovenous fistula.

In order to understand the prevalence of Akabane disease(AKAD)in Guizhou Province and the molecular characteristics of the isolates,the whole-genome sequence of a strain of Akabane virus(AKAV)from a bovine AKAD-positive sample was determined and analyzed.The genotype and genetic variation of the strain were also explored.Based on the conserved S sequence,a fluores-cence quantitative PCR(qPCR)detection method was established and applied for the investigation of AKAV infection status in four large-scale beef cattle farms of Guizhou.Results showed that the S,M and L fragments of the bovine strain were highly homologous to the Tianjin strain(TJ2016/China/2016)and the Australian strain(JaLAB39/Australia/1959),where they were in the same evolutionary branch and belonged to genotype Ⅱ.Sensitivity assay found that the lowest detection limit was 2.5 X 101 copies/μL.Specificity assay showed the established method detected only AKAV with no amplification on bovine bluetongue virus(BLUV),Pasteurella multocida(PM),bovine infectious rhinotracheitis virus(IBRV)and bovine Mycoplasma bovis.The variation coefficients of inter-and intra batches in the repeatability test were both lower than 2.26％.These findings illus-trated that the established qPCR method had high sensitivity,good specificity and repeatability.A total of 298 serum samples from 4 large-scale beef cattle farms in Qianxi City and Huangping County of Guizhou Province were collected and tested for AKAV by the method.Out of 298 sam-ples,25 positive samples(25/298)were detected as positive with a positive rate of 8.39％.In sum-mary,this work provided the reference data for a deep understanding of the molecular prevalence of AKAV in Guizhou Province and laid foundation for the prevention and control of AKAD.

Objective:To investigate the relationship between IGF2BP3 gene expression and prognosis in patients with acute myeloid leukemia(AML).Methods:High throughput transcriptome sequencing was performed on bone marrow primary leukemia cells from 27 patients with AML in our center,the relationship between IGF2BP3 expression levels and clinical characteristics were analyzed and verify the samples from patients with newly treated AML and refractory AML.The expression level of IGF2BP3 gene were analyzed in 20 healthy subjects and 26 patients with AML.The expression of IGF2BP3 in two anthracycline-resistant cell lines(HL60/ADR,K562/ADR)was detected by RT-qPCR and Western blot,and the expression difference of IGF2BP3 was compared with that in sensitive cells(HL60,K562).The relationship between the expression level of IGF2BP3 in patients with AML and prognostic were analyzed through data analysis of 746 patients with AML,and the prognostic value of IGF2BP3 in AML was analyzed by multivariate Cox regression analysis.Results:In the bone marrow primary leukemia cells of 27 AML patients in our center,the expression level of IGF2BP3 in patients with refractory AML was significantly higher than that in chemotherapy sensitive patients(P=0.0343).The expression of IGF2BP3 in leukemia patients with extramedullary infiltration(EMI)was significantly higher than that in AML patients without extramedullary infiltration(P=0.0049).Compared with healthy subjects(n=20),IGF2BP3 expression in AML patients(n=26)was higher(P=0.0009).The expression of IGF2BP3 mRNA in the anthracycline resistant cell lines(HL60/ADR,K562/ADR)was significantly higher than that in the sensitive cell lines(K562/ADR vs K562,P=0.0430;HL60/ADR vs HL60,P=0.7369).Western blot results showed that the expression of IGF2BP3 protein in mycin resistant cells was significantly higher than that in sensitive cells(P＜0.001).qPCR results showed that the expression level of IGF2BP3 mRNA in refractory AML patients was significantly higher than that in patients with chemotherapy sensitive(P=0.002).High expression of IGF2BP3 was associated with poor prognosis in AML(P＜0.05)in 3 large sample cohorts of AML patients.Univariate and multivariate prognostic analyses demonstrated that high expression of IGF2BP3 was significantly associated with shorter event-free survival(EFS,HR=1.887,P=0.024)and overall survival(OS,HR=1.619,P=0.016).Conclusion:The high expression of IGF2BP3 gene may be an important factor in the poor prognosis of AML,suggesting that IGF2BP3 gene may be a new molecular marker for the clinical prognosis evaluation and treatment strategy of AML.

Objective:To analyze the related factors of treatment failure in children with acute lymphoblastic leukemia (ALL)in real-world.Methods:The clinical data of 1414 newly diagnosed children with ALL admitted to five hospital in Fujian province from April 2011 to December 2020 were retrospectively analyzed.Treatment failure was defined as relapse,non-relapse death,and secondary tumor.Results:Following-up for median time 49.7 (0.1-136. 9)months,there were 269 cases (19.0％)treatment failure,including 140 cases (52.0％)relapse,and 129 cases (48.0％)non-relapse death.Cox univariate and multivariate analysis showed that white WBC≥50 ×109/L at newly diagnosis,acute T-cell lymphoblastic leukemia (T-ALL),BCR-ABL1,KMT2A-rearrangement and poor early treatment response were independent risk factor for treatment failure (all HR>1.000,P<0.05).The 5-year OS of 140 relapsed ALL patients was only 23.8％,with a significantly worse prognosis for very early relapse (relapse time within 18 months of diagnosis).Among 129 patients died from non-relapse death,71 cases (26.4％)were died from treatment-related complications,56 cases (20.8％)died from treatment abandonment,and 2 cases (0.7％)died from disease progression.Among them,treatment-related death were significantly correlated with chemotherapy intensity,while treatment abandonment were mainly related to economic factors.Conclusion:The treatment failure of children with ALL in our province is still relatively high,with relapse being the main cause of treatment failure,while treatment related death and treatment abandonment caused by economic factors are the main causes of non-relapse related death.

Objective To compare the clinical outcomes of all-inside arthroscopic and open recon-struction of the anterior talofibular ligament(ATFL)and calcaneofibular ligament(CFL).Methods The clinical data of 51 patients with chronic lateral ankle instability(CLAI)and treated in our department between January 2017 and July 2021 were analyzed retrospectively.Among them,24 received ar-throscopic ATFL and CFL reconstruction(arthroscopy group),while 27 underwent conventional surgery(open group).The perioperative data including surgical time,intraoperative complications,hospitaliza-tion duration and time to resume normal walking were compared between the two groups.Moreover,postoperative CT examination was performed to evaluate the position of the bone tunnel.Before as well as 3 months,6 months,1 year,and 2 years after the operation,both groups were evaluated using the American Orthopedic Foot and Ankle Society Score(AOFAS),Karlsson score,visual analogue scale(VAS),drawer test,and inversion test.Meanwhile,the occurrence of complications was also recorded and compared.Results Both groups underwent the surgery successfully.The total length of incision and time to resume normal walking in the arthroscopy group were significantly shorter than the open group(P<0.05),while there was no significant difference between them in surgical time and hospital stay(P>0.05).Postoperative CT showed that in the arthroscopy group,1 case had suboptimal talus bone tun-nel position,while in the open group,1 had suboptimal calcaneus bone tunnel position and another suffered from suboptimal talus bone tunnel position,with the remaining bone tunnels located within the corresponding footprint area.All patients were followed up for 24 to 33 months.Significant improve-ment was observed in the average AOFAS score,Karlsson score,and VAS score in both groups after the operation(P<0.05),and both the drawer and inversion tests were of negative results.Three months postoperatively,the arthroscopic group had significantly better AOFAS,Karlsson and VAS score than the open group(P<0.05).Moreover,at 6 months postoperatively,the average AOFAS and Karlsson scores of the arthroscopy group were significantly superior to the open group(P<0.05).However,1 year and 2 years postoperatively,no significant differences were found between the two group in the AOFAS,Karlsson and VAS score(P>0.05).Moreover,no serious complications occurred during surgery and follow-up in both groups.Conclusion The efficacy of arthroscopic reconstruction of ATFL and CFL is comparable to open reconstruction in treating CLAI,with the former therapy resulting in faster recov-ery.

Aim To study the effect of Guben Yanling pills on liver aging in aging mice and the related mech-anism.Methods The mice were randomly divided in-to blank control group,model group,vitamin E group(0.1 g·kg-1)and low,medium and high dose groups(0.59,1.17,2.34 g·kg-1)of Guben Yan-ling pills.The aging mouse model was established by subcutaneous injection of D-galactose(150 mg·kg-1)into the back of neck.At the same time of mod-eling,the corresponding drugs were given by gavage once a day for six weeks.The main organ indexes were calculated.HE staining was used to observe the mor-phology of liver tissue.Colorimetry was used to detect the activity of β-galactosidase in liver.ELISA was used to detect the content of TNF-α,IL-1 β,IL-6,IL-4,IL-10.Western blot was used to detect the protein relative expression level of IKKβ,Iκ Bα,NF-κB p65.Immunofluorescence was used to detect the expression level of NF-κB p65.Results Compared with the blank control group,the organ index of the brain,liv-er,kidney,spleen,and thymus in the model group decreased(P＜0.05,P＜0.01),the activity of β-galactosidase increased(P＜0.01),liver tissue mor-phology and structure were significantly damaged,the content of TNF-α,IL-1 β and IL-6 increased(P＜0.01),the content of IL-4 and IL-10 decreased(P＜0.01),the levels of IKKβ,NF-κB p65 in-creased(P＜0.01),the levels of IKBα decreased(P＜0.01),and the levels of NF-κB p65 in nucleus increased(P＜0.01).Compared with the model group,the organ indexes of brain,liver,kidney,spleen,and thymus in each dose group of Guben Yan-ling pills increased(P＜0.05,P＜0.01),the activity of β-galactosidase decreased(P＜0.01),the morpho-logical and structural damage of liver tissue was signifi-cantly improved,the content of TNF-α,IL-1 β and IL-6 decreased(P＜0.01),the content of IL-4 and IL-10 increased(P＜0.01),the levels of IKKβ,NF-κB p65 decreased(P＜0.01),the levels of IκBα in-creased(P＜0.01),and the levels of NF-κB p65 in nucleus decreased(P＜0.01).Conclusions Guben Yanling pills can antagonize liver aging in mice,and its mechanism may be related to inhibiting the activa-tion of NF-κB signaling pathway in liver,downregulat-ing downstream pro-inflammatory factor levels,upregu-lating anti-inflammatory factor levels,and alleviating inflammation in liver.