BACKGROUND:Osteosarcoma has a complex pathogenesis and a poor prognosis.While advancements in medical technology have led to some improvements in the 5-year survival rate,substantial progress in its treatment has not yet been achieved. OBJECTIVE:To screen key molecular markers in osteosarcoma,analyze their relationship with osteosarcoma treatment drugs,and explore the potential disease mechanisms of osteosarcoma at the molecular level. METHODS:GSE99671 and GSE284259(miRNA)datasets were obtained from the Gene Expression Omnibus database.Differential gene expression analysis and Weighted Gene Co-expression Network Analysis(WGCNA)on GSE99671 were performed.Functional enrichment analysis was conducted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes separately for the differentially expressed genes and the module genes with the highest positive correlation to the disease.The intersection of these module genes and differentially expressed genes was taken as key genes.A Protein-Protein Interaction network was constructed,and correlation analysis on the key genes was performed using CytoScape software,and hub genes were identified.Hub genes were externally validated using the GSE28425 dataset and text validation was conducted.The drug sensitivity of hub genes was analyzed using the CellMiner database,with a threshold of absolute value of correlation coefficient|R|>0.3 and P<0.05. RESULTS AND CONCLUSION:(1)Differential gene expression analysis identified 529 differentially expressed genes,comprising 177 upregulated and 352 downregulated genes.WGCNA analysis yielded a total of 592 genes with the highest correlation to osteosarcoma.(2)Gene Ontology enrichment results indicated that the development of osteosarcoma may be associated with extracellular matrix,bone cell differentiation and development,human immune regulation,and collagen synthesis and degradation.Kyoto Encyclopedia of Genes and Genomes enrichment results showed the involvement of pathways such as PI3K-Akt signaling pathway,focal adhesion signaling pathway,and immune response in the onset of osteosarcoma.(3)The intersection analysis revealed a total of 59 key genes.Through Protein-Protein Interaction network analysis,8 hub genes were selected,which were LUM,PLOD1,PLOD2,MMP14,COL11A1,THBS2,LEPRE1,and TGFB1,all of which were upregulated.(4)External validation revealed significantly downregulated miRNAs that regulate the hub genes,with hsa-miR-144-3p and hsa-miR-150-5p showing the most significant downregulation.Text validation results demonstrated that the expression of hub genes was consistent with previous research.(5)Drug sensitivity analysis indicated a negative correlation between the activity of methotrexate,6-mercaptopurine,and pazopanib with the mRNA expression of PLOD1,PLOD2,and MMP14.Moreover,zoledronic acid and lapatinib showed a positive correlation with the mRNA expression of PLOD1,LUM,MMP14,PLOD2,and TGFB1.This suggests that zoledronic acid and lapatinib may be potential therapeutic drugs for osteosarcoma,but further validation is required through additional basic experiments and clinical studies.

Objective To investigate the clinical characteristics,treatment methods,and prognosis of a-cute leukemia patients with extramedullary infiltration.Methods The clinical characteristics and treatment methods of 47 acute leukemia patients with extramedullary infiltration admitted to the Affiliated Hospital of Guizhou Medical University from April 2014 to April 2023 were retrospectively analyzed.Subgroup analysis was performed according to whether there was extramedullary infiltration before transplantation,and whether there was isolated extramedullary recurrence after transplantation.Based on this analysis,the patients were di-vided into the pre-transplantation radiotherapy group and pre-transplantation non-radiotherapy group,the post-transplantation radiotherapy group and post-transplantation non-radiotherapy group.According to the treatment methods of central nervous system leukemia(CNSL),the patients were divided into the intrathecal injection group(n=12)and combination of intrathecal injection and radiotherapy group(n=13).The local remission situation,survival duration,and toxic and side effects of radiotherapy and chemotherapy were com-pared.Results For acute leukemia patients with extramedullary infiltration,the overall survival time(OS)in the radiotherapy group was better than that in the non-radiotherapy group(median OS:706 d vs.151 d,P=0.015).Subgroup analysis showed that the OS of the pre-transplantation radiotherapy group was better than that of the pre-transplantation non-radiotherapy group(median OS:592 d vs.386 d,P=0.035).For CNSL,the combination of intrathecal injection and radiotherapy group had a better OS than the intrathecal injection group(median OS:547 d vs.388 d,P=0.045).The event-free survival time(EFS)of the radiotherapy group was better than that of the non-radiotherapy group(median EFS:175 d vs.50 d,P=0.005).The COX pro-portional-hazards model showed that treatment with or without radiotherapy had a significant impact on the OS of acute leukemia patients with extramedullary infiltration.The risk of death in the pre-transplantation non-radiotherapy group was 2.231 times higher than that in the pre-transplantation radiotherapy group(HR=3.231,95％CI:1.021-10.227,P=0.046).Compared with the non-radiotherapy group,the radiother-apy group had a higher local remission and a lower risk of haematological toxicity,infection,and haemorrhage.Conclusion Radiotherapy can rapidly alleviate the local symptoms of acute leukemia complicated with extr-amedullary infiltration,prolong the survival time of these patients,and reduce the risk of hematologic toxicity,infection,and haemorrhage.

Platycodonis Radix is the dry root of Platycodon grandiflorum of Campanulaceae, which has a variety of pharmacological effects and is a commonly used bulk Chinese medicine. In this study, the chloroplast genome sequences of six P. grandiflorum from different producing areas has been sequenced with Illumina HiSeq X Ten platform. The specific DNA barcodes were screened, and the germplasm resources and genetic diversity were analyzed according to the specific barcodes. The total length of the chloroplast genome of 6 P. grandiflorum samples was 172 260-172 275 bp, and all chloroplast genomes showed a typical circular tetrad structure and encoded 141 genes. The comparative genomics analysis and results of amplification efficiency demonstrated that trnG-UCC and ndhG_ndhF were the potential specific DNA barcodes for identification the germplasm resources of P. grandiflorum. A total of 305 P. grandiflorum samples were collected from 15 production areas in 9 provinces, for which the fragments of trnG-UCC and ndhG_ndhF were amplificated and the sequences were analyzed. The results showed that trnG-UCC and ndhG_ndhF have 5 and 11 mutation sites, respectively, and 5 and 7 haplotypes were identified, respectively. The combined analysis of the two sequences formed 13 haplotypes (named Hap1-Hap13), and Hap4 is the main genotype, followed by Hap1. The unique haplotypes possessed by the three producing areas can be used as DNA molecular tags in this area to distinguish from the germplasm resources of P. grandiflorum from other areas. The haplotype diversity, nucleotide diversity and genetic distance were 0.94, 4.79×10^-3 and 0.000 0-0.020 3, respectively, suggesting that the genetic diversity was abundant and intraspecific kinship was relatively close. This study laid a foundation for the identification of P. grandiflorum, the protection and utilization of germplasm resources, and molecular breeding.

OBJECTIVE To establish a performance index evaluation system for pharmacists in inpatient pharmacy to encourage and guide pharmacists to achieve self-professional growth and reshape their own values. METHODS According to the evaluation criteria for the construction of provincial-level clinical specialties in Jiangsu province, the key success factors(KSF) method was used to set the key indicators for the discipline construction of the department, and the key process indicator(KPI) method was used for the daily work of the department. Based on the combination of KSF and KPI, an inpatient pharmacy performance management system was established, employee and clinical satisfaction, ward complaints, error occurrence rate, dispensing efficiency, and scientific research output were taken as indicators to evaluate the effect after the implementation of the performance management system. RESULTS Before and after the construction and implementation of the "KSF + KPI" performance system, the average employee satisfaction had increased from 57.75% to 77.81%(P<0.05), the number of complaints in the ward had decreased from (26.33±6.75) per month to (7.17±3.61) per month, and the number of errors had decreased from (30.33±5.50) per month to (12.58±2.75) per month, the differences were statistically significant(P<0.05). Overall clinical satisfaction reached 81.13%; the PIVAS blending efficiency had been improved to a certain extent, with an average increase of 17%. Innovation related indicators such as article writing, recruitment, project application, and employee research participation had significantly improved after implementation of the indicator performance system. CONCLUSION The inpatient pharmacy performance management system establishes based on "KSF and KPI" provides a good performance evaluation scheme for the transformation and development of the dispensing department of the pharmaceutical department. It has made positive exploration in the aspects of self-motivation and professional development of hospital pharmacists, high-efficiency operation, improvement of clinical service level and development of pharmaceutical discipline, and has achieved good results.

Objective To analyze the clinical characteristics of 310 patients with anti-tuberculosis drug-induced liver injury(ATB-DILI),to explore prognostic influencing factors,and to provide reference for its prevention and treatment.Methods Primary tuberculosis patients hospitalized in the Department of Tuberculosis of the Third People's Hospital of Kunming from November 2020 to November 2022 who met the diagnosis of ATB-DILI were enrolled.Statistics by gender,age,history,type of tuberculosis,co-morbidities,frequency of anti-tuberculosis regimens leading to liver injury,use of hepatoprotective drugs,and management and regression were performed to analyze the clinical characteristics of the patients and the factors influencing their prognosis.Results 310 patients were included,male,148(47.74%)and female,162(52.26%).The mean age was 44.33±17.47 years.Thirty-four patients had a history of allergy.The combination of isoniazid,rifampicin,pyrazinamide,and ethambutol(244 patients,78.71%)was the anti-tuberculosis regimen that resulted in the highest number of cases of hepatic injury.The median time between initiation of the tuberculosis regimen and the development of hepatic injury in patients with ATB-DILI was 30 d,and the mean duration of hospitalization was 16.39±7.01 d.The most used hepatoprotective drug was reduced glutathione(154 patients,49.68%),and most patients used a combination of 2 hepatoprotective drugs(128 patients,41.29%).Liver injury improved in 257 cases(82.90%)and failed in 53 cases(17.10%).The differences in alcohol consumption,severity,clinical staging,TT,ALP,TBIL,DBIL,IBIL,and GGT were statistically significant compared to those who did not recover(P<0.05),and severity and high ALP were independent risk factors for poor prognosis.Conclusions Patients should be carefully asked if they have a history of basic liver disease and alcoholism before using anti-tuberculosis drugs.In the course of anti-tuberculosis treatment,the combined use of anti-tuberculosis drugs is more serious than the use of single drugs to cause liver damage.Drugs that may cause liver damage should be used with caution and improved anti-tuberculosis programs should be explored.At the same time,liver function should be monitored regularly during anti-tuberculosis treatment,especially 30 days after medication,in order to reduce the occurrence of adverse reactions.

Objective To observe the intervention effect of hypericin(HYP)on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease(PD)mice model and its mechanism.Methods Thirty C57BL/6 mice were randomly divided into normal,model and experimental groups with 10 mice per group.PD mouse model was established after 7 days of intraperitoneal injection of MPTP,and drug intervention was carried out from the first day of modeling.Normal group and model group were intraperitoneally injected with 500 μL·kg·d-1 0.9％NaCl.The experimental group was intraperitoneally injected with 25 mg·kg·d-1 HYP.The three groups of rats were given the drug once each time for 14 days.The expression levels of tyrosine hydroxylase(TH),Nod-like receptor thermal protein domain protein 3(NLRP3)and ionized calcium binding adapter molecule 1(Iba1)in the striatum of nigra were detected by Western blot.Results The climbing time of normal,model and experimental groups was(5.35±0.43),(9.71±1.19)and(8.07±0.34)s;suspension scores were(2.92±0.15),(1.38±0.28)and(1.96±0.28)points;the relative expression levels of TH protein were 1.04±0.06,0.51±0.09 and 0.75±0.07;the relative expression levels of NLRP3 protein were 0.51±0.03,1.00±0.04 and 0.77±0.06;the relative expression levels of Iba1 protein were 0.68±0.10,1.30±0.28 and 0.89±0.05,respectively.The above indexes in the model group were statistically significant compared with the experimental group and the normal group(all P＜0.01).Conclusion HYP plays a therapeutic role in PD by inhibiting the expression of NLRP3 inflammasome in PD mice.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Background and purpose:The plasma used for routine coagulation test(CCT)can only reflect a single component at a certain coagulation time point/segment,while thromboelastography(TEG)can depict the overall dynamic process curve of coagulation and fibrinolysis,which can more independently and completely reflect the true state of the blood and can serve as a supplement to coagulation function testing.This study aimed to evaluate the application value of combined coagulation function indexes in monitoring the hypercoagulable state of patients with colorectal cancer after chemotherapy,and to explore the risk factors of thrombosis in patients with colorectal cancer after chemotherapy,so as to provide reference for clinical monitoring of hypercoagulable state.Methods:A total of 160 patients with colorectal cancer from Fudan University Shanghai Cancer Center from June 2021 to June 2023 were selected as the experimental group,and 80 healthy subjects were selected as the control group.Then the experimental group was divided into a group without thrombosis(82 cases)and a group with thrombosis(78 cases)according to whether they had thrombosis or not.The determinations of thromboelastography(TEG)[coagulation reaction time(R),coagulation formation time(K),blood clot formation rate(α-Angle),maximum amplitude(MA)and coagulation index(CI)],conventional coagulation tests(CCT)[activated partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),fibrinogen(Fib),D-dimer(DD),fibrinogen degradation products(FDP)]and platelet count(PLT)were studied among three groups.With or without thrombosis as the criterion of hypercoagulable state,statistically significant indicators were selected to be included in the binary logistic regression analysis,and the receiver operating characteristic(ROC)curve was drawn to analyze the diagnostic efficacy of single and combined detection of the coagulation function indicators for hypercoagulable state in patients with colorectal cancer after chemotherapy.Basic information,tumor stage and Autar score of deep vein thrombosis were collected in 160 patients with colorectal cancer.Logistic regression analysis was performed to explore the risk factors of thrombosis.This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center(number:050432-4-2108*).Results:Compared with the control group,the R,TT and PLT of the group with thrombosis were decreased(P＜0.05),while APTT,PT,DD and FDP were increased(P＜0.05).The differences in various indicators between the group with thrombosis and the control group were statistically significant(P＜0.05).Compared with the group without thrombosis,the K in the group with thrombosis decreased(P＜0.05),while Angle,MA,CI,FIB,DD and FDP all increased(P＜0.05).ROC curve analysis showed that in the assessment of hypercoagulable state in patients with colorectal cancer after chemotherapy,the area under curve(AUC)of TEG was 0.756,sensitivity was 67.5%,and specificity was 73.8%.The AUC of CCT was 0.691,sensitivity was 78.8%,and specificity was 56.2%.The combined detection AUC was 0.840,sensitivity was 80.0%,and specificity was 77.5%.In the analysis of risk factors,tumor stage,distant metastasis and Autar score were correlated with thrombus formation in patients with colorectal cancer after chemotherapy(P＜0.05),and the differences of the three risk factors in K,Angle,MA,CI,Fib,DD and FDP were statistically significant(P＜0.05).Conclusion:K,Angle,MA,CI,Fib,DD and FDP are the main indicators to reflect the hypercoagulable state,and the combined detection of TEG and CCT can better reflect the coagulation state of patients with colorectal cancer after chemotherapy.Tumor stage Ⅲ to Ⅳ,distant metastasis and high Autar score are risk factors for thrombosis.The incidence of thrombosis can be reduced by monitoring the relevant coagulation indicators in the high-risk population.

Objective To explore the value of droplet digital polymerase chain reaction(ddPCR)in the etiological diagnosis of severe acute pancreatitis(SAP)patients with suspected bloodstream infection(BSI).Methods SAP patients admitted to the department of critical care medicine in a hospital July to September 2022 were enrolled.When BSI was suspected,venous blood was collected for both ddPCR detection and blood culture(BC)with antimi-crobial susceptibility testing(AST)simultaneously.The time required for two detection methods was recorded,and the detection results of ddPCR and BC were compared.The etiological diagnostic efficacy of ddPCR was calculated,and the correlation between the value of pathogen load detected by ddPCR and the level of infection parameters was explored.Results A total of 22 patients were included in the analysis,and 52 venous blood specimens were collec-ted for detection.BC revealed 17 positive specimens(32.7％)and 29 pathogenic strains,while ddPCR showed 41 positive specimens(78.8％)and 73 pathogenic strains.Detection time required for ddPCR was significantly lower than that of BC([0.16±0.03]days vs[5.92±1.20]days,P＜0.001).Within the detection range of ddPCR and taking BC results as the gold standard,the sensitivity and specificity of ddPCR were 80.0％and 28.6％,respective-ly.With the combined assessment of BSI based on non-blood specimen microbial evidence within a week,the sensi-tivity and specificity of ddPCR detection increased to 91.9％and 76.9％,respectively.ddPCR detected resistance genes of blaKPC,blaNDM/IMP,VanA/VanM,and mecA from 19,9,6,and 5 specimens,respectively.Correlation analysis showed a positive correlation between pathogen load and levels of C-reactive protein as well as procalcitonin(r=0.347,0.414,P＜0.05).Conclusion As a supplementary detection method for BC in BSI diagnosis,ddPCR has the advantages of higher sensitivity and shorter detection time,and is worthy of further exploration in clinical application.

Objective To understand the respiratory protection competency of staff in hospitals.Methods Staff from six hospitals of different levels and characteristics in Beijing were selected,including doctors,nurses,medical technicians,and servicers,to conduct knowledge assessment on respiratory protection competency.According to exposure risks of respiratory infectious diseases,based on actual cases and daily work scenarios,content of respira-tory protection competency assessment was designed from three aspects:identification of respiratory infectious di-seases,transmission routes and corresponding protection requirements,as well as correct selection and use of masks.The assessment included 6,6,and 8 knowledge points respectively,with 20 knowledge points in total,all of which were choice questions.For multiple-choice questions,full marks,partial marks,and no mark were given respective-ly if all options were correct,partial options were correct and without incorrect options,and partial options were correct but with incorrect options.Difficulty and discrimination analyses on question of each knowledge point was conducted based on classical test theory.Results The respiratory protection competency knowledge assessment for 326 staff members at different risk levels in 6 hospitals showed that concerning the 20 knowledge points,more than 60％participants got full marks for 6 points,while the proportion of full marks for other questions was relatively low.Less than 10％participants got full marks for the following 5 knowledge points:types of airborne diseases,types of droplet-borne diseases,conventional measures for the prevention and control of healthcare-associated infec-tion with respiratory infectious diseases,indications for wearing respirators,and indications for wearing medical protective masks.Among the 20 knowledge questions,5,1,and 14 questions were relatively easy,medium,and difficult,respectively;6,1,4,and 9 questions were with discrimination levels of ≥0.4,0.30-0.39,0.20-0.29,and ≤0.19,respectively.Conclusion There is still much room for hospital staff to improve their respiratory protection competency,especially in the recognition of diseases with different transmission routes and the indications for wearing different types of masks.