Objective:To investigate the targets and mechanisms of cycloastragenol in ameliorating azithromycin-induced drug-induced liver injury(DILI)based on network pharmacology and in vitro experiment validation.Methods:Potential targets of cycloastragenol and DILI were predicted using databases.The common and key targets were screened and subjected to GO and KEGG enrichment analyses,as well as molecular docking validation.Primary hepatocytes from C57BL/6 mice were isolated.The optimal concentration and time for azithromycin-induced DILI in mouse primary hepatocytes were determined using CCK8 and ROS assays.The expression of genes and proteins such as NF-κB p65,p-NF-κB p65,AMPKα,and p-AMPKα was assessed using RT-qPCR and Western blot to evaluate the intervention effect of cycloastragenol(10-50 μmol/L).Results:Network pharmacology analysis identified 10 key genes related to cycloastragenol's improvement of DILI,including heat shock protein 90AA1(HSP90AA1),matrix metalloproteinase 2(MMP2),etc.GO enrichment analysis suggested that cycloastragenol primarily regulates biological processes such as membrane potential and chemical synaptic transmission,and affects cellular components such as neuronal cell bodies and distal axons,and related kinase activities.KEGG enrichment analysis showed that it mainly exerts intervention effects through neuro-signaling pathways and IL-17 signaling pathways.Molecular docking demonstrated strong binding of cycloastragenol to HSP90AA1,MMP2,NF-κB p65,AMPKα,nuclear factor erythroid 2-related factor 2(Nrf2),heme oxygenase 1(HO-1),and NAD(P)H:quinone oxidoreductase 1(NQO1),with a binding energy≤-5.0 kcal/mol for Nrf2.In vitro experiments showed that azithromycin(50 μmol/L,12 h)significantly reduced hepatocyte viability and increased ROS levels(P＜0.01).Different concentrations of cycloastragenol significantly improved the activity of mouse primary hepatocytes,reduced the generation of intracellular ROS,downregulated the phosphorylation level of NF-κB p65,and upregulated the mRNA and protein levels of AMPKα,Nrf2,HO-1,NQO1(P＜0.05).Conclusions:Cycloastragenol may alleviate azithromycin-induced hepatocyte oxidative stress and inflammation by inhibiting NF-κB phosphorylation and activating the AMPK/Nrf2/HO-1/NQO1 pathway,with its mechanism likely closely linked to targeting Nrf2.However,the complex mechanisms of DILI may involve additional unverified pathways.Therefore,further studies are necessary to validate the efficacy and safety of cycloastragenol in animal models.

Objective To design a Five-Elements Music Software based on Traditional Chinese Medicine's(TCM)theory of five elements music therapy and music emotion classification.The software is intended to provide appropriate music selections tailored to the negative emotional states of cancer patients and evaluate its effectiveness in psychological rehabilitation.Methods ①Music screening and classification:Qualitative analysis was used by six experts in TCM,psychology,nursing,and musicology to screen five elements music and classify corresponding emotional categories.②Software design and development:Based on screening and classification of music materials,design and develop a"Five Elements Music Software Based on Emotion Classification".③Software application evaluation:Recruit 50 cancer patients from the"Beijing Anti Cancer Paradise"as participants to have a trial listening experience with music software,and fill out a satisfaction questionnaire to evaluate its application effect.Results This study established a music database containing 150 pieces of five-elements musical tunes and completed the classification of emotional categories.Among the included subjects,80%of the recruited objects were satisfied with the experience of the five elements music software,of which the application experience of female patients was significantly better than that of male patients,and breast cancer patients were better than other cancer patients,with a statistically significant difference(P<0.05).The five elements music Software in clinic showed comparing with other two groups after four weeks,there was a significant difference for HAMD when comparing five elements music software group and the other two groups(P<0.05).Conclusion The five-element music software designed based on emotion classification effectively meets the psychological rehabilitation needs of cancer patients.It provides appropriate music selections and convenient listening method to regulate cancer-related negative emotions,extending psychological rehabilitation from the hospital to the home.

Objective:To establish an early warning model of oral infection risk in patients with acute leukemia undergoing chemotherapy and to verify its predictive efficacy, so as to provide reference for formulating strategies to prevent oral infections.Methods:A retrospective study was conducted to select 288 patients with acute leukemia undergoing chemotherapy from January 2021 to January 2023 in Hematology Hospital of Chinese Academy of Medical Sciences (Institute of Hematology, Chinese Academy of Medical Sciences) as the training set. According to whether they developed oral infection after chemotherapy, they were divided into the infected group and the non-infected group. The risk factors of oral infection in patients with acute leukemia undergoing chemotherapy were investigated, and a risk warning model was established. A total of 246 acute leukemia undergoing chemotherapy patients admitted to the same hospital from February 2023 to February 2024 were selected as the validation set to conduct external verification of the model.Results:The oral infection rate was 19.44% (56/288) in the training set. There were 21 males and 35 females in the infected group (56 cases), with 49 cases<60 years old and 7 cases ≥60 years old. There were 102 males and 130 females in the non infected group (232 cases), with 196 cases<60 years old and 36 cases ≥60 years old. Multivariate analysis showed that neutrophil count <1.5×10 9/L, nutritional risk screening 2002≥3 points, high-dose of methotrexate, antibiotic types ≥3, poor oral self-cleaning habits, oral pH ≤6.5 were the risk factors for oral infection in patients with acute leukemia undergoing chemotherapy ( OR values were 2.716-10.074, all P<0.05). Based on this, the risk early warning model was as follows: Logit ( P)=-5.849+2.310× neutrophil count <1.5×10 9/L+1.363× nutritional risk screening 2002≥3 points +1.150× high-dose methotrexate +1.132× antibiotic types ≥3 + 1.044× oral pH ≤6.5 + 0.999× poor oral self-cleaning habits. The area under receiver operator characteristics curves (ROC) curve of this model Logit ( P) was 0.892, the maximum approximate entry index was 0.653, the sensitivity was 0.804, and the specificity was 0.849. Hosmer-Lemeshow test results indicated that χ2=4.91, P=0.768. For external validation, the goodness of fit test results were χ2=6.47, P=0.595. The area under ROC curve was 0.884, the sensitivity was 0.832, and the specificity was 0.825. Conclusions:The established early warning model of oral infection risk in patients with acute leukemia undergoing chemotherapy has good predictive value, which is helpful for medical staff to conduct early risk assessment of oral infection in such patients, and formulate countermeasures to reduce the incidence and improve the treatment effect of the disease.

Objective:To construct an evaluation system for the risk factors of PICC catheter malposition in patients with hematological diseases, providing a reference for the prevention of central venous access malposition in these patients.Methods:From July 2022, a literature review was conducted to retrieve literature published in database and website such as PubMed, Web of Science domestically and internationally related to the risk assessment system of PICC catheter malposition in hematology patients. After full-text screening and extraction, the articles were included in the system′s item pool. Through further discussions among the research group′s experts, in conjunction with evidence-based findings, the system′s consultation items were formulated. Using the Delphi expert consultation method, a standard for PICC catheter malposition risk assessment system applicable to hematology patients was ultimately formulated.Results:In this study, 25 experts were invited for consultation: 24 females and 1 male, with an average age of (48.36 ± 6.82) years. After two rounds of expert consultations and revisions, the risk factors for PICC catheter malposition in hematology patients were identified to include 4 first-level indicators: patient factors, treatment factors, catheter-related factors, and operational factors, along with 11 second-level indicators and 25 third-level indicators. The positive coefficients of the experts in the two rounds of consultations were 84% and 100%, respectively; the Kendall coordination coefficients were 0.22 and 0.55 (both P<0.05); and the expert authority coefficient was 0.93. Conclusions:The risk assessment scale for PICC catheter malposition in patients with hematological diseases has high expert recognition and good consistency, and has clinical practice and guiding value.

OBJECTIVE To investigate the drug resistance genes,virulence genes and capsule serotypes of hyper-mucoviscous Klebsiella pneumoniae(HMKP)from a hospital,providing a reference for clinical anti-infective treatment.METHODS A total of 46 non-repetitive HMKP strains,isolated and identified from clinical samples in the First People's Hospital of Chuzhou from Jul.to Dec.2023,were collected.Drug susceptibility testing was per-formed,and drug resistance genes,virulence genes and capsule serotypes were amplified by polymerase chain re-action(PCR).The PCR products were determined by genetic sequencing and comparison.Multilocus sequence typing(MLST)was used for molecular epidemiological typing,and eBURST was used to analyze strain homology.RESULTS The 46 HMKP strains were mainly isolated from ICU(28.26％,13 strains)and respiratory departments(23.91％,11 strains).The primary specimen type was respiratory specimens(91.30％,42 strains).The drug re-sistance rates of HMKP to the monitored antibacterial drugs were all＜10％.PCR results showed that only 1 strain carried the CTX-M1 drug resistance gene.The predominant capsule serotypes were K2(16 strains,34.78％),K1(7 strains,15.22％)and K57(7 strains,15.22％).The detection rates of the five virulence genes were as follows:ae robactin(46 strains,100.00％),kfu(46 strains,100.00％),rmp A(43 strains,93.48％),iroNB(42 strains,91.30％),rmpA2(37 strains,80.43％)and magA(31 strains,67.39％).Among the 46 HMKP strains,22 sequence types(STs)were identified,with ST86(9 strains,19.56％),ST25(8 strains,17.39％),ST23(5 strains,10.87％),ST412(5 strains,10.87％)and ST65(2 strains,4.35％)being the most prevalent.Homology analysis conducted by eBURST software revealed that 18 STs had relatively close genetic relationships.CONCLUSIONS Only 1 strain of clinically isolated HMKP carries the CTX-M1 gene,with the predominant capsule serotypes being K2,K1 and K57.The detection rates of virulence genes aerobactin and kfu are 100.00％.The K2 serotype carries multiple virulence gene patterns,and the STs are mainly ST86,ST25,ST23 and ST412.There is a clear evolutionary relationship among HMKP strains.

Objective To observe the value of ultrasound combined with hematologic tests for diagnosing acute complicated appendicitis.Methods Data of 225 patients with acute appendicitis confirmed by surgery and postoperative pathology were retrospectively analyzed.The patients were divided into acute complicated appendicitis group(complicated group,n=33)and acute uncomplicated appendicitis group(uncomplicated group,n=192)based on operational and post operation pathological findings.Clinical data,hematologic test results and ultrasound findings before operation were compared between groups.Multivariate logistic regression was used to construct a combination model for diagnosing acute complicated appendicitis.Receiver operating characteristic(ROC)curve and area under the curve(AUC)were used to evaluate the diagnostic value of predictive factor alone and their combination for diagnosing acute complicated appendicitis,which were then compared with DeLong test.Results Compared with uncomplicated group,patients in complicated group were older,with higher proportion of fever and vomiting,higher level of C reactive protein(CRP)and of neutrophil-to-lymphocyte ratio(NLR),larger external diameters of appendix,also higher proportion of appendiceal intracavitary fecalith and periappendiceal abscess(all P＜0.05).Multivariate logistic regression analysis showed that elevated serum CRP and NLR,increased external diameter of appendix and periappendiceal abscess were all predictive factors of acute complicated appendicitis(all P＜0.05).The diagnostic efficiency of logistic regression model constructed based on the above factors(AUC=0.854)was higher than that of each single predictive factor alone(Z=2.548-4.527,all P＜0.05).Conclusion Ultrasound combined with hematologic tests had high value for diagnosing acute complicated appendicitis.

Objective:To compare the effects of intraoperative administration or non-administration of tranexamic acid (TXA) on early postoperative inflammatory response and clinical outcomes in elderly male patients with intertrochanteric femur fractures.Methods:A retrospective cohort study was conducted to analyze the clinical data of 92 elderly male patients with intertrochanteric femur fractures admitted to Zhongda Hospital Affiliated to Southeast University from January 2020 to December 2022, aged 62-96 years [(79.9±8.4)years]. According to the modified Evans classification, the fractures were classified as types I-III in 33 patients and types IV-V in 59. All the patients were treated with proximal femoral intramedullary nail fixation. Among them, 46 patients received intraoperative TXA (TXA group), while 46 patients did not (non-TXA group). The operative duration, intraoperative blood loss, length of postoperative hospital stay were compared between the two groups. The serum interleukin-6 (IL-6) levels and visual analogue scale (VAS) scores at 1, 3, 5, and 7 days postoperatively were detected. The complication rate and mortality within 1 year postoperatively were also compared between the two groups.Results:All the patients were followed up for 1-12 months [(10.9±2.8)months]. No significant difference was found in the operative duration between the groups ( P>0.05). The intraoperative blood loss and length of postoperative hospital stay were 150.0(100.0, 200.0)ml and (6.8±1.9)days in the TXA group, less or shorter than those in the non-TXA group [200.0(150.0, 262.5)ml and (7.7±2.0)days] ( P<0.05). At 1, 3, and 5 days postoperatively, the IL-6 levels in the TXA group were 84.5(66.3, 100.1)pg/ml, 48.9(36.8, 61.2)pg/ml, and 27.9(19.4, 37.5)pg/ml, which were all lower than those in the non-TXA group [110.3(83.1, 162.9)pg/ml, 63.7(44.2, 84.2)pg/ml, and 32.7(22.4, 42.9)pg/ml] ( P<0.05). No statistically significant difference in the IL-6 level was observed between the two groups at 7 days postoperatively ( P>0.05). At 1 and 3 days after operation, the VAS scores in the TXA group were (4.3±0.9)points and (2.5±0.9)points, lower than those in the non-TXA group [(6.8±1.2)points and (3.0±1.2)points] ( P<0.05). There were no statistically significant differences in VAS scores between the two groups at 5 and 7 days postoperatively ( P>0.05). The complication rate within one year after operation was 28% (13/46) in the TXA group, significantly lower than 50% (23/46) in the non-TXA group ( P<0.05). No significant difference was observed in the mortality within 1 year postoperatively between the two groups ( P>0.05). Conclusion:Compared with non-administration of TXA, intraoperative administration of TXA can effectively reduce the intraoperative blood loss, shorten the length of postoperative hospital stay, significantly lower early postoperative inflammation levels, reduce early postoperative pain intensity, and decrease the incidence of complications in elderly male patients with intertrochanteric femur fractures, with no significant difference in mortality within 1 year after operation between the two groups.

Objectives:To investigate the physical growth status of pediatric patients with transfusion-dependent thalassemia (TDT) and analyze the effects of treatment-related and socioeconomic factors on physical growth.Methods:Based on the specialized thalassemia database from gene therapy clinical research at the Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, we collected data on height and weight development, family economic status, and medical records of 338 pediatric patients with TDT from October 2023 to May 2024. The length/height-for-age and body mass index (BMI) -for-age were classified based on the Growth Standard for Children under 7 Years of Age, Standard for Height Level Classification among Children and Adolescents Aged 7-18 Years, and Dietary Guidelines for Chinese Residents. Logistic regression analysis was conducted to assess the effects of family economic status and disease-related treatment on length/height-for-age and BMI-for-age.Results:Among the 338 patients, 118 were children and 220 were adolescents (192 males and 146 females), with a median age of 12 years (range: 0.8-18) and a median diagnosis duration of 10.3 years (range: 0.5-17.9). Subtypes included α-thalassemia [21 cases (6.2%) ], β-thalassemia [288 cases (85.2%) ], and combined αβ-thalassemia[29 cases (8.6%) ]. The monthly household income of patients was concentrated in 3 000-5 000 yuan (39.9%) and 5 001-10 000 yuan (34.9%), whereas 67.2% of the families had monthly medical expenses of <3 000 yuan. Of the patients, 75.5% received their first transfusion before 1 year of age. The proportions of children and adolescents with pretransfusion hemoglobin (HGB) of ≤70 g/L were 4.2% and 6.4%, respectively. Adolescents demonstrated significantly higher rates of transfusion frequency of <4 weeks/session, monthly red blood cell infusion of >2 U, serum ferritin (SF) of ≥5 000 μg/L, iron chelation therapy, and splenectomy compared with children (all P<0.05). Of the 338 patients, 26.0%, 22.8%, and 8.9% demonstrated stunted growth, underweight, and concurrent stunted growth with underweight, respectively. No significant difference was observed in the stunted growth rates between children (22.9%) and adolescents (27.7%) ( P=0.402). However, the underweight rate in adolescents (26.8%) was significantly higher than that in children (15.3%) ( P=0.023). The multivariate analysis determined the following risk factors for stunted growth: monthly household income of <10 000 yuan (5 001-10 000 yuan: OR=5.49, 95% CI: 1.48-35.76; 3 000-5 000 yuan: OR=6.87, 95% CI: 1.88-44.60; <3 000 yuan: OR=9.29, 95% CI: 2.20-64.77), pretransfusion HGB of ≤70 g/L ( OR=3.25, 95% CI: 1.07-10.18), and SF of ≥5 000 μg/L ( OR = 3.04, 95% CI: 1.20-7.70). Longer diagnostic duration was associated with underweight ( OR=1.10, 95% CI: 1.01-1.20) . Conclusions:Children and adolescents with TDT with pretransfusion SF of ≥5 000 μg/L, HGB of ≤70 g/L, low monthly household income, or longer diagnosis duration were significantly more likely to experience delayed physical growth.

Objective:To identify the prognostic value of the Revised 15-item Myelodysplastic Syndrome-specific frailty scale (FS-15) in Chinese patients with myelodysplastic syndromes (MDS) .Methods:This retrospective study analyzed 812 patients with newly diagnosed MDS admitted to the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College from August 2016 to June 2023. Patients were assessed using the FS-15 and subsequently categorized into frail and non-frail groups. Clinical and laboratory characteristics, as well as overall survival (OS), were compared between these groups.Results:① The median patient age was 55 years ( IQR 45–64), with a median follow-up of 22.5 months (95% CI: 20.2–24.9) and a median OS of 43.3 months (95% CI: 36.8–49.8). The median FS-15 score was 0.42, with a cutoff value of 0.44. Male patients demonstrated higher median FS-15 scores than female patients (0.42 vs 0.38, P=0.006). In both the Revised International Prognostic Scoring System (IPSS-R; P=0.001) and Molecular International Prognostic Scoring System (IPSS-M; P=0.014) stratifications, FS-15 scores were significantly higher in the very high-risk group compared with the very low-risk group. ② The median OS was 54.7 months (95% CI: 47.5–NA) and 31.5 months (95% CI: 22.9–41.0) in the nonfrail ( n=452) and frail groups ( n=360), respectively ( P<0.001). The 3-year OS rates were (63.2 ± 3.2) % and (46.4 ± 3.6) % for the non-frail and frail groups, with 5-year OS rates of (49.9 ± 4.7) % and (32.0 ± 4.3) %, respectively ( P<0.001). ③Subgroup analysis revealed that nonfrail patients demonstrated significantly higher 3-year OS rates than frail patients in both the IPSS-M low-risk and very high-risk groups (all P<0.05). Similarly, nonfrail patients demonstrated superior 3-year OS rates compared with frail patients in the IPSS-R very low-risk, low-risk, and high-risk groups (all P<0.05). ④Among patients receiving hypomethylating agent therapy, the overall response rate was significantly higher in the non-frail group than in the frail group (86.7% vs 64.6%, P=0.007). Moreover, the frail group experienced higher rates of treatment-related adverse events, including febrile neutropenia (67.1% vs 47.4%, P=0.016) and liver function abnormalities (30.0% vs 14.5%, P=0.023), compared with the non-frail group. Conclusion:The FS-15 frailty score is a feasible and effective tool for assessing frailty in patients newly diagnosed with MDS in China and serves as a valuable prognostic indicator.

Objective:To explore the risk fall death associated with compound hot extremes.Methods:This study collected data on fall deaths in Guangdong, Hunan, and Zhejiang Provinces from 2013 to 2018 and matched their exposure to meteorological data. Based on a time-stratified case-crossover design, a conditional logistic regression model embedded with a cross-basis function of the distributed lag nonlinear model was applied to estimate the risk of fall to death due to compound hot extremes.Results:Compared with regular days, compound hot extremes significantly increased the risk of death from falls ( OR=1.19, 95% CI: 1.09-1.30), and women ( OR=1.27, 95% CI: 1.11-1.45) and the elderly age 65 and above ( OR=1.24, 95% CI: 1.12-1.39) were more sensitive to compound hot extremes. The maximum duration of compound hot extremes was 7 days, and the maximum intensity was 6.2 ℃, and the duration and intensity were proportional to the risk of death from falls. The risk of death from falls increased by 12% ( OR=1.12, 95% CI: 1.06-1.18) each day, increasing in duration after linearization. The risk of death from falls increased by 16% ( OR=1.16, 95% CI: 1.10-1.22) for each 1 ℃ increase in linearized intensity. Conclusion:Compound hot extremes increase the risk of death cases from falls.