Objective To explore the effect of chemotherapeutic drugs doxorubicin or cisplatin on lipid metabolism of macrophages and its regulatory mechanism.Methods Macrophage RAW264.7 was treated with doxorubicin or cisplatin,and intracellular lipid level was detected by oil red O and ELISA;RNA sequence screen-ing and Western blot were used to confirm the changes of gene expression after chemotherapeutic drug treatment;The effects of silencing ROBO3 on cellular lipid metabolism were explored,and changes in key target genes of lipid metabolism were detected by Q-PCR and western blot.Results Adriamycin or cisplatin induced disturbances in macrophage cholesterol metabolism and exacerbated macrophage foaminess.Further studies showed that the expression of the axon guidance factor receptor,ROBO3,increased and then decreased during the chemotherapeutic drug-induced macrophage foaming process.Further intervention with ROBO3 exacerbates oxldl-induced cholesterol accumulation and foam formation in macrophages.Mechanistically,ROBO3 deficiency promotes the expression of cholesterol synthesis-related gene DHCR24 and inhibits the expression of cholesterol elimination-related gene ABCG1,resulting in cholesterol accumulation in macrophages.Conclusion This study found that ROBO3 plays an important regulatory role in the disruption of cholesterol metabolism and its foaming process in macrophages induced by chemotherapeutic drugs,which may provide new targets and ideas for the prevention and treatment of chemotherapy-related atherosclerosis.

AIM:To determine the link between infliximab,adalimumab,vedolizumab,ustekinumab and risk of lymphoma in order to provide reference for the safety of clinical application.METHODS:Dis-proportionality analysis and Bayesian analysis were used in data mining to screen the suspected lym-phoma after the use of four biological agents based on the FAERS data from October 2012 to June 2023.The fatality and hospitalization rates of this four biological agents associated lymphoma were also investigated.RESULTS:Totally 705 cases of four biological agents associated lymphoma were collected.Four biological agents associated lymphoma appeared to influent more young pa-tients and middle-aged patients than elderly pa-tients(25.11％vs.22.41％vs.12.2％).There were slightly more male than females(42.84％vs.35.60％).Infliximab has the highest reporting odds ratio[ROR3.40,95％CI=(3.03,3.82)],proportional ratio[PRR3.38,95％CI=(3.01,3.79)],information component(IC1.14,IC-2SD=1.02)and empirical Bayes geometric mean(EBGM2.21,EBGM05=2.01).Significant difference in the fatality rate and hospi-talization rate among four biological agents were not found.CONCLUSION:Infliximab showed a strongest lymphoma association than the other three biological agents.Lymphoma risk should be vigilant when using infliximab.

Objective To evaluate the cost-effectiveness of roxadustat and darbepoetin alfa on treating renal anemia in dialysis-dependent chronic kidney disease(DD-CKD)patients,thus providing health economics reference for treatment of renal anemia.Methods A Markov model simulating the development and treatment of anemia in DD-CKD patients in a lifetime horizon(20 years)was constructed.Total costs of roxadustat and darbepoetin alfa injection were estimated from the perspective of Chinese healthcare system,with health outcomes converted into quality-adjusted life year(QALY).The incremental cost-effectiveness ratio(ICER)was used to describe the results.The willingness-to-pay(WTP)threshold was set at 257 094 yuan,which was three times China's gross domestic product(GDP)per capita in 2023.Sensitivity analyses were performed to test the uncertainties of the results.Results The total treatment costs of roxadustat and darbepoetin alfa injection were 111 902.41 yuan and 52 927.92 yuan respectively,corresponding to QALY values of 4.76 and 4.74 life-years.The incremental cost-effectiveness(ICER)was 2 654 912.45 yuan/QALY,which exceeded 3 times GDP per capita.Therefore,compared with darbepoetin alfa injection,roxadustat has no cost-effectiveness for patients with DD-CKD.Conclusion In the context of current economic development in China,darbepoetin alfa injection is more cost-effective than roxadustatin for treating anemia in DD-CKD patients.

Objective:This study aimed to evaluate the global research landscape, identify trends, and determine hotspots concerning hepatoma recurrence post-liver transplantation.Methods:We conducted a bibliometric analysis usinga systematic search was conducted in the Web of Science Core Collection database from Jan. 1992 to Oct. 2023 to identify relevant articles on hepatoma recurrence after liver transplantation. Articles were selected based on inclusion and exclusion criteria and analyzed for publication trends by country/region, journal, author, institution, citation, and keyword. Visualization tools such as Citespace, VOSviewer, and Bibliometric.com were utilized for statistical analysis, identification of emerging trends, and clustering of keyword co-occurrence.Results:Out of 4,936 articles retrieved, 1,189 were included in the final analysis. There was a notable increase in publications on hepatoma recurrence following liver transplantation from 1992 to 2021, peaking in 2021 both globally (n=103) and nationally (n=32). China has the largest number of publications in this field (n=308), maintaining significant collaboration with the United States, South Korea, Japan, Canada. 'Liver Transplantation’ journal had the highest number of publications (n=113). Zhejiang University was the leading institution (n=74), with Academician Zheng Shusen being the most prolific scholar (n=76 publications). Citation emergence detection found that Italian scholar Mazzaferro's Predicting survival after liver transplantation in patients with hepatocellular carcinoma beyond the Milan criteria: a retrospective, exploratory analysis published on The Lancet Oncology in 2009 had the highest burst strength (36.98). Five bursting keywords were identified: alpha fetoprotein, model, validation, sorafenib, and risk. Cluster analysis of keyword co-occurrence revealed five primary research themes: the medication for hepatocellular carcinoma recurrence after liver transplantation, recipient selection criteria, prognostic factors, development and validation of recurrence prediction model, and local treatments for hepatocellular carcinoma.Conclusions:The study underscores rapid advancements in the research on hepatocellular carcinoma recurrence post-liver transplantation over the past three decades, with significant contributions from Chinese scholars, particularly from Zhejiang University and Academician Zheng Shusen. The evolving research hotspots have shifted from transplantation experiences and recipient selection criteria to early post-transplant recurrence risk prediction and therapeutic strategy development.

Objective:To explore health utility value, evaluate health-related quality-of-life(QOL)of pediatric liver transplantation(LT)recipients and examine its influencing factors to provide rationales for related health economic evaluations.Methods:This cross-sectional QOL was conducted through a questionnaire in pediatric LT recipients aged 5-17 years.The interviewees undergoing initial LT from June 2013 to September 2021 were reviewed regularly.Those children and their parents unwilling to participate or failing to understand the contents of questionnaire were excluded.The questionnaire was designed on the basis of Child Health Utility 9D Instrument(CHU9D)and answered online by one of primary caregiver.Chinese score system of CHU9D was employed for converting the responses into health utility values and the influencing factors were analyzed.Univariate analysis was performed by nonparametric tests and multivariate analysis by multiple linear regression model. P<0.05 was deemed as statistically significant. Results:A total of 140 valid questionnaires were obtained.Mean age of pediatric LT recipients was(7.95±2.74)years and mean postoperative time(4.90±2.17)years.Among them, 19 cases had experienced acute rejection and 101(72.1%)cases were living-related LT recipients.CHU9D scale indicated that average health utility value was(0.85±0.14)points.Univariate analysis revealed that age( P=0.008), education level( P<0.001)and primary disease( P=0.010)influenced the postoperative level of QOL.Multivariate analysis indicated that QOL was correlated with education level(behind schedule: 95% CI: -0.146, -0.034, P=0.002; leave of absence: 95% CI: -0.251, -0.068, P=0.001). Conclusions:Health utility of pediatric LT recipients is high with an excellent QOL.Poor QOL is associated with absence from school or dropping out of school.

Objective:To investigate the association between plasma uric acid and hypertension and the gender difference in community-dwelling middle-aged and elderly population.Methods:A community-based cross-sectional study was conducted in Beijing Tongzhou Yongshun Community Health Service Center from June to December 2021, among residents aged 45 years or older selected by cluster sampling method. According to plasma uric acid (UA) level in quartiles, the subjects were divided into 4 groups; and stratified by gender, the subjects were further divided into subgroups. Multivariate logistic regression model was used to analyze the related factors of hypertension, and restricted cubic spline fitting logistic regression model was used to analyze the nonlinear association between uric acid and hypertension and the cut-off values of uric acid.Results:A total of 6 229 residents with the age of (63.2±7.3) years were enrolled in the study. In 1 874 male participants (30.1%), 946 participants (50.5%) had hypertension, and the uric acid level was 359 (309, 418)μmol/L; in 4 355 female participants (69.9%), 2 003 participants (46.0%) had hypertension, and the uric acid level was 306 (261, 359)μmol/L. Multivariate logistic regression analysis showed that after adjusting for factors that were statistically significant in univariate analyses or potentially clinically relevant (including age, body mass index, diabetes mellitus, coronary heart disease, cerebrovascular disease, albumin, estimated glomerular filtration rate, and cholesterol), uric acid was independently associated with hypertension ( P<0.001), for total participants the risk of hypertension in Q4 group was 1.33 times of that in Q1 group ( OR=1.33,95% CI 1.13-1.56, P=0.001); while for females the risk of hypertension in Q4 group was 1.38 times of that in Q1 group ( OR=1.38,95% CI 1.13-1.68, P=0.002), but no significant association was observed for males ( P>0.05). The results of restricted cubic spline fitting logistic regression analysis showed that there was a linear association between uric acid level and hypertension in the total population and males, and the risk of hypertension increased with uric acid level ( P<0.001 for the total population, P=0.016 for male). However, there was a non-linear association in females. When uric acid>307 μmol/L in females, the risk of hypertension increased significantly as the level of uric acid increased ( P<0.001). Conclusions:Uric acid level was independently associated with hypertension in the community-dwelling middle-aged and elderly population, and there was a gender difference in the correlation. The association was nonlinear in females and the cut-off value of uric acid in females was 307 μmol/L.

Objective To provide a reliable and stable animal model for investigating the molecular pathogenesis of radiation-induced liver disease (RILD). Methods Ninety C57BL/6J mice were divided into control, 20 Gy, 25 Gy, 30 Gy and 35 Gy radiation groups. The mice were executed at 4 weeks after radiation and the levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase in the liver serum were measured. HE staining was performed on the pathological liver tissues. Masson staining was performed at 36 weeks after radiation. Results Compared with the control group, the fatality rate was higher in the 30 and 35 Gy radiation groups, and the body weight significantly decreased in the 20 and 25 Gy radiation groups. Compared with the control group, alanine aminotransferase significantly increased in mice exposed to 20 Gy, while aspartate aminotransferase and alanine aminotransferase increased in mice exposed to 25 Gy. No significant changes were observed in the livers of the mice in the 20 and 25 Gy radiation groups, but pathological examination showed liver damage induced by both 20 and 25 Gy radiation. Conclusion A stable and reliable mouse model of RILD was constructed for treatment with linear accelerator. The mouse model of RILD constructed for stereotactic body radiation therapy using linear accelerator has significant research implications for the exploration of RILD.

Objective To investigate the characteristics of adverse drug reactions(ADRs)induced by tislelizumab and to provide reference for clinic drug safety.Methods The ADR of tislelizumab in Beijing Friendship Hospital Affiliated to Capital Medical Univeristy from July 2021 to December 2022 were retrospectively analyzed.The case reports of ADR induced by tislelizumab from January 2019 to December 2022 in PubMed,ScienceDirect,Embase,Wanfang,VIP databases were searched.Age,sex,original diseases,adverse reaction time,clinical manifestation,treatment measures and clinical outcome were analyzed.Results A total of 30 patients including 8 cases in hospital and 22 cases in literature were collected.Among these patients,male accounted for 83.33%(25/30),and the highest proportion was from patients over 60 years old(21 patients,70.00%).Most ADRs occurred in 1-2 dose cycles of medication,mainly including skin toxicity in 8 patients,digestive disease in 6 patients and kidney injury in 4 patients.After the symptomatic treatment,29 patients improved and 1 patient died.Conclusion During the medication with tislelizumab,ADRs of skin,gastrointestinal tract and renal should be vigilant,and the changes of relevant indicators should be closely monitored.

Objective To investigate the medical expense control model of rational drug use based on the China healthcare security diagnosis related groups(CHS-DRG)simulation in Beijing in 2021.Methods By analyzing the simulated operation data from January to March 2021 before the intervention,the groups with rational drug management improving potential among the top three surgical disease groups in terms of the number of cases enrolled in the surgical department were selected.Then,the targeted intervention and guidance were implemented to the selected disease groups.Finally,the analysis was obtained by comparing the changes in several key indicators such as the average drug cost,average antibacterial drug cost,average surplus and average length of stay during June to August 2021.Moreover,the differences in antimicrobial drug use intensity and hospital infection reporting of the department as a whole where the problematic groups were located were also investigated.Results Before the intervention,the otolaryngology related groups(including DD29 and DE19),urology surgery related groups(including LD19 and LJ13)could be improved in antibacterial drug use during the perioperative period.Meanwhile,the chest surgery related group(including EB19)had space to be improved in auxiliary medication.After the intervention,the five groups'average drug cost and average antibacterial drug cost in the otolaryngology and urology surgery departments are all decreased.The antibiotics use intensity is also declined in otolaryngology and urology surgery departments.The average surplus of otolaryngology and urology surgery related groups are increased,with the DE19 disease group in ENT also achieving a profit turnaround.As for the indicators related to the quality of care,there were no significant differences in the groups'average length of stay and nosocomial infection reporting of these departments.Conclusion The hospital operation based on CHS-DRG payment is both an opportunity and a challenge.The all-inclusive payment model has prompted hospitals to take the initiative in controlling costs,and the exploration of a rational medication management and cost-control model related to disease groups has begun to show results in terms of cost reductions without affecting the quality of medical care.The research can also provide a solid foundation for the CHS-DRG actual payment and sustainable development of medical insurance fund.

Objective:To explore the distribution of pathogenic bacteria during perioperative period of kidney transplantation(KT)patients and examine drug resistance of major clinical pathogens to commonly used antibiotics to provide references for empirical medication of pathogenic bacteria infection after KT.Methods:From January 1, 2020 to June 30, 2021, 251 patients undergoing deceased donation KT on kidney transplant ward were selected.Clinical samples were collected and distribution and drug resistance of pathogenic bacteria examined for analyzing the incidence of possible donor-derived infections and predicting prognoses.Results:The detection rate of pathogens was 12.18%(367/3 014). A total of 225 non-repetitive strains were isolated.Gram-positive bacteria, Gram-negative bacteria and fungi accounted for 48.89%(110/225), 43.11%(97/225)and 8.00%(18/225). The proportion of lavage fluid in all isolated bacteria was 49.78%(112/225). And Staphylococcus epidermidis and Klebsiella pneumoniae predominated.Drainage fluid accounted for 24.88%(56/225)and Pseudomonas putida and Staphylococcus haemolyticus predominated.Urine accounted for 18.67%(42/225)with a dominance of Enterococcus faecium; blood accounted for 6.22%(14/225)with a dominance of S. epidermidis.All detected pathogens showed varying degrees of resistance.The resistance rates of E. faecium to ampicillin, vancomycin and linezolid were 93.33%(28/30), 6.45%(2/31)and 38.71%(12/31). The resistance rates of K. pneumoniae and Acinetobacter baumannii to carbapenems were 71.43%(20/28)and 80.00%(12/15). The incidence of possible donor-derived infection was 3.59%(9/251)and there was no mortality.Conclusions:The detection rate of pathogenic bacteria is high in KT patients during perioperative period.There is a diverse distribution of isolates of different specimen types and all detected pathogens show varying degrees of drug resistance.Clinicians should regularly analyze the distribution characteristics and causes of drug-resistant bacteria.And antibiotics should be optimized according to the results of drug sensitivity.