OBJECTIVE: To explore the clinical significance of circulating tumor DNA (ctDNA) in response evaluation and relapse monitoring for patients with primary mediastinal large B-cell lymphoma (PMBCL). METHODS: The clinical characteristics, efficacy and survival of 38 PMBCL patients in our hospital from January 2010 to April 2020 were retrospectively analyzed. The ctDNA monitoring was conducted by targeted next-generation sequencing (NGS). RESULTS: Among the 38 patients, 26 cases were female, and 32 cases were diagnosed with Ann Arbor stage I-II. The 5-year overall survival (OS) rate and progression-free survival (PFS) rate were 74.7% and 61.7%, respectively. Males and those with high aaIPI scores (3 points) had a relatively poor prognosis. The NGS results of 23 patients showed that STAT6 (65.2%), SOCS1 (56.5%), and TNFAIP3 (56.5%) were the most common mutated genes. Patients with stable disease (SD)/progressive disease (PD) exhibited enrichment in cell cycle, FoxO, and TNF signaling pathways. A total of 29 patients underwent end-of-treatment PET/CT (EOT PET/CT), and 16 of them received ctDNA monitoring with 12 negative. Among 6 patients with EOT PET/CT positive (Deauville 4), 4 underwent ctDNA monitoring, and 3 of them were negative, being still in continuous remission without any subsequent anti-tumor therapy. CONCLUSION CtDNA may be combined with PET/CT to assess efficacy, monitor relapse, and guide treatment of PMBCL.
Humans ; Circulating Tumor DNA/blood* ; Female ; Mediastinal Neoplasms ; Male ; Retrospective Studies ; High-Throughput Nucleotide Sequencing ; Prognosis ; Lymphoma, Large B-Cell, Diffuse/genetics* ; Middle Aged ; Adult ; Aged ; Neoplasm Recurrence, Local ; Mutation

OBJECTIVE: To analyze the gene mutation characteristics and survival time of patients with newly diagnosed acute myeloid leukemia (AML) based on next-generation sequencing(NGS) gene detection. METHODS: A retrospective analysis was conducted on the clinical data of 92 patients with AML (non APL) admitted to our hospital from January 2018 to May 2022. AML related genes tested were using NGS, the mutation characteristics and survival time of AML patients were analyzed. RESULTS: Among the 92 patients, 41 were males and 51 were females. A total of 38 types of gene mutations were detected. Six-two patients carried at least one gere mutation, while no gene mutations were detected in 30 patients. In the group with favourable prognosis (n =14), the frequencies of higher gene mutations were NRAS, KIT (21.43%, n =3), KRAS (14.29%, n =2). In the group with intermediate prognosis (n =64), the gene mutation frequencies from high to low were DNMT3A (18.75%, n =12), NPM1 (17.19%, n =11), IDH2, FLT3-ITD, CEBPA (12.50%, n =8), TET2 (10.94%, n =7). In the poor prognosis group (n =14), ASXL1, TP53, EZH2, NRAS had higher gene mutation frequency than others(14.29 %, n =2 ). Statistical analysis revealed that KIT had a relative hotspot of mutations in the intermediate-risk group, and DNMT3A had a relative hotspot of mutations in the high-risk group (P < 0.05). The correlation analysis of genes with high mutation rates in different prognostic groups, such as NRAS, KIT, IDH2, DNMT3A, NPM1, and FLT3-ITD, with prognosis found that KIT was a factor affecting OS (P < 0.05), while no significant differences were observed for the others(P >0.05). CONCLUSION The frequency of gene mutations is high in AML patients, 67.4% of the patients carried at least one gene mutation. The mutation frequency varies among different genes in patients with different karyotypes, and there are obvious dominant mutations. KIT and DNMT3A can be used as factors for evaluating the prognosis of AML.
Humans ; Leukemia, Myeloid, Acute/genetics* ; Nucleophosmin ; Mutation ; Prognosis ; Retrospective Studies ; Male ; Female ; High-Throughput Nucleotide Sequencing ; Middle Aged ; DNA Methyltransferase 3A ; Adult ; Aged ; Survival Analysis ; Proto-Oncogene Proteins c-kit/genetics*

OBJECTIVE: This study aimed to determine the expression levels and prognostic significance of MYCN in bone marrow of adult patients with newly diagnosed acute myeloid leukemia (AML). METHODS: A total of 62 newly diagnosed patients with non-M3 AML were enrolled as the study group, and 20 healthy donors as the control group. Real-time quantitative reverse transcription-polymerase chain reaction (PCR) was performed to detect the expression level of MYCN, and the relationship between MYCN expression and prognosis of AML patients was analyzed. RESULTS: MYCN was up-regulated in newly diagnosed AML patients compared with normal controls (P < 0.001). Receiver operating characteristic (ROC) curve analysis revealed that MYCN could serve as a diagnostic biomarker for AML. Kaplan-Meier survival analysis showed that the patients with high MYCN expression had a shorter overall survival (OS) time than the patients with low MYCN expression (P =0.016). The expression level of MYCN was lower during the complete ressimion (CR) phase of AML compared to the initial diagnosis, but it returned to the initial diagnostic level or even higher during relapse phase. Multivariate Cox regression analysis showed that high expression of MYCN was an independent risk factor for OS of AML patients (P =0.021). CONCLUSION MYCN is highly expressed and associated with poor prognosis in de novo AML, which might be serve as a novel diagnostic and prognostic biomarker for adult AML.
Humans ; Leukemia, Myeloid, Acute/metabolism* ; Prognosis ; N-Myc Proto-Oncogene Protein ; Adult ; Female ; Male ; Middle Aged

OBJECTIVE: To investigate the predictive value of morphology, immunology, and cytogenetics for isocitrate dehydrogenase 1 and 2 (IDH1/2) gene mutation in newly diagnosed acute myeloid leukemia (AML) patients. METHODS: The clinical data of 186 newly diagnosed AML patients (except M3 subtype) in the First People's Hospital of Changzhou were retrospectively analyzed, and the variables associated with IDH1/2 mutation in patients were screened using LASSO regression to construct a multivariate logistic regression analysis model. The Bootstrap method was used for internal validation of the model and nomograms were used to visualize the model, and receiver operating characteristic (ROC) curve was used to evaluate the predictive performance of the model. RESULTS: A total of 60 AML patients had IDH1/2 mutation at initial diagnosis. LASSO regression screened 9 predictive variables associated with IDH1/2 mutation, including CD7, CD56, CD11b, CD15, CD64, HLA-DR, platelet count≥50×10⁹/L, isolated +8 and normal karyotype. The nomogram and ROC curve were plotted based on the above 9 variables. The area under the ROC curve (AUC) of the training set and the validation set were 0.871 and 0.806, respectively. Internal validation showed that the nomogram had good predictive ability. CONCLUSION The prediction model based on MIC typing constructed in this study has a good predictive ability for the presence of IDH1/2 mutations in newly diagnosed AML patients and has important clinical application value when the gene mutation detection results are unavailable.
Humans ; Isocitrate Dehydrogenase/genetics* ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Retrospective Studies ; Nomograms ; Female ; Male ; ROC Curve ; Middle Aged

BACKGROUND:Studies have shown that there are significant differences in the geometric morphology of the distal femur of different races and genders,and there are more short female patients in southern China,so the phenomenon of overhanging or insufficient coverage of imported knee prostheses often occurs during surgery. OBJECTIVE:To investigate the characteristics of distal femur bones in southern Chinese women and compare them with imported joint prostheses by simulating the three-dimensional reconstruction of the distal femur bone and matching the femoral side after osteotomy with common imported joint prostheses. METHODS:From January to December 2021,120 female volunteers underwent a CT scan of knee joints.The images were imported into Mimics 20.0 software in Dicom format for three-dimensional reconstruction and then imported into Magic 22.0 software to simulate osteotomy by posterior cruciate ligament preserved total knee arthroplasty and to conduct a matching study with a normal imported joint prosthesis. RESULTS AND CONCLUSION:(1)The functional anteroposterior dimension(fAP)of the distal femur and Persona matched prosthesis had a total overhang rate of 25%(30/120).The fAP≤47 mm group had an overhang than the other groups(P<0.05).The poor coverage rate of Triathlon prosthesis was 12.5%(15/120),and poor coverage was more likely in fAP>53 mm group than in fAP≤53 mm group(P<0.05).(2)The total poor coverage rate of femoral intercondylar width matching with Triathlon prosthesis was 27.5%(33/120).Therefore,the poor coverage rate of bone surface in the central region of the distal femur was more likely in the fAP≤47 mm group than in other groups(P<0.05).The overhang rate of Journey II was 21.6%(26/120),and the overhang rate was higher in the fAP>53 mm group than in the fAP≤53 mm group(P<0.05).(3)Journey II CR prosthesis had the largest difference with the length of the anterior mediolateral diameter of the femur,which was easy to hang out on the anterolateral side of the femoral prosthesis.The Persona CR prosthesis has the largest difference with the length of the posterior mediolateral diameter of the femur,which is easy to be poorly covered in the posterior medial part of the prosthesis.It is recommended to increase the femoral prosthesis with reduced mediolateral diameter in the fAP≤47 mm group and add wider and narrower sizes than the conventional size of intercondylar width,and optimize the anterolateral angular arc design of the femoral prosthesis to improve the matching of posterior cruciate ligament reserved knee prosthesis.

Objective:To investigate the prognostic significance of DTA(DNMT3A,TET2,ASXL1)gene mutations in patients with non-M3 acute myeloid leukemia(AML).Methods:The clinical data of 180 newly diagnosed AML patients hospitalized in the First People's Hospital of Changzhou from January 2018 to April 2022 were retrospectively analyzed.Next-generation sequencing technology was used to detect 150 gene mutations in the patients,and log-rank tests and Cox regression models were used to analyze the prognostic factors.Results:DTA gene mutations were detected in 83(46.1％)of 180 AML patients.Compared to patients without DTA mutations,patients with DTA mutations were significantly older(P＜0.001).The median overall survival(OS)time and disease-free survival(DFS)time in the DTA mutation group were significantly shorter than those in the group without DTA mutation(both P＜0.05).Multivariate analysis showed that age ≥ 60 years(P＜0.001),with DTA mutation(P=0.018),and intermediate-risk(relative to favorable-risk)(P=0.005)were independent risk factors for OS in AML patients.Conclusion:AML patients with DTA mutations are relatively older,with shorter median OS time and DFS time,and poor prognosis.

Objective:To explore the therapeutic efficacy and prognostic factors of induction therapy for secondary central nervous system lymphoma(SCNSL).Methods:Clinical data of patients diagnosed with SCNSL from 2010 to 2021 at Guangdong Provincial People's Hospital were retrospectively collected.A retrospective cohort study was performed on all and grouped patients to analyze the efficacy and survival.Multivariate logistic regression analysis was used to explore the adverse prognostic factors.Results:Thirty-seven diffuse large B-cell lymphoma patients with secondary central involvement were included in the research.Their 2-year overall survival(OS)rate was 46.01％and median survival time was 18.1 months.The 2-year OS rates of HD-MTX group and TMZ group were 34.3％and 61％,median survival time were 8.7 and 38.3 months,and median progression-free survival time were 8.1 and 47 months,respectively.Multivariate logistic regression analysis showed that age,sex,IPI,Ann Arbor stage were correlated with patient survival time.The median survival time of patients with CD79B,KMT2D,CXCR4.ERBB2,TBL1XR1,BTG2,MYC,MYD88,and PIM1 mutations was 8.2 months,which was lower than the overall level.Conclusion:HD-MTX combined with TMZ as the first-line strategy may improve patient prognosis,and early application of gene sequencing is beneficial for evaluating prognosis.

Objective:To investigate the 10-years risk for cardiovascular diseases(CVD) among different subtypes of pre-diabetes(Pre-DM) residents aged 40 and above in Guiyang urban area and to analyze the influencing factors.Methods:A total of 5 798 residents who participated in the " Risk Evaluation of cAncers in Chinese diabe Tic Individuals: a lONgitudinal(REACTION) Study" were selected to undergo oral glucose tolerance test and glycated hemoglobin test. According to the Pre-DM diagnostic criteria, normal glucose tolerance(NGT), impaired fasting glucose(IFG), impaired glucose tolerance(IGT), and diabetes mellitus were defined based on glycated hemoglobin(IA1C), and were combined into four groups: NGT group, single subtype group(IFG, IGT, IA1C), two-subtype combination group(IFG+ IGT, IFG+ IA1C, IGT+ IA1C), and three-subtype combination group(IFG+ IGT+ IA1C). Ten-year cardiovascular disease occurrence was investigated. The logistic regression model was used to analyze the risk of CVD occurrence in different subtypes of Pre-DM residents. Results:(1)The incidence in the single subtype group, two subtypes group and three subtypes group of CVD was 6.6%(182/2 752), 8.4%(135/1 613) and 9.6%(53/551) , respectively, all higher than NGT group at 5.2%(46/882). (2) Regardless of diagnosed by fasting blood glucose, 2 h blood glucose, or glycated hemoglobin, the 10-year CVD incidence rates(8.7%, 8.6%, 7.6%) in Pre-DM were higher than that in the NGT group(5.2%; all P<0.05). (3)After multivariate adjustment, compared with the NGT group, the 10-year CVD risk gradually increased in the single subtype group, two-subtype group, and three-subtype group, with OR of 1.03(95% CI 0.74-1.45), 1.08(95% CI 0.75-1.54), and 1.16(95% CI 0.75-1.78), respectively. Conclusion:The Pre-DM population has a higher 10-year risk for CVD, and the risk increases gradually with the accumulation of subtypes. Therefore the prevention and treatment of CVD should focus on the management of the Pre-DM population.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective To investigate the effect of inhibiting the expression of RNA component of mitochondrial RNA processing endoribonuclease(RMRP)on the proliferation and invasion of human lung cancer cell line A549 in order to provide evidence to support the research on NSCLC mechanism.Methods A total of 122 cases of patients who underwent surgical treatment were selected in Jiaozuo People's Hospital from March 2016 to March 2021.In the same period,50 healthy people from physical examination center were selected as the control group.RT-qPCR was used to detect the expressions of RMRP in blood and tissues.Human lung cancer cell line A549 was cultured and divided into si-RMRP group,siRNA-NC group and blank group.RT-qPCR,CCK-8 and Transwell assays were used to detect the expression of RMRP,proliferation activity and cell counting of invasive cells.Results The rel-ative expression level of RMRP in the blood of NSCLC patients was significantly higher than that of control group(P<0.001).The relative expression level of RMRP in NSCLC tissues was significantly higher than the adjacent tissues(P<0.001).The relative expression level of RMRP in blood and tissues of patients with poorly differenti-ated,lymph node metastasis and TNM stage Ⅲ compared with moderate to highly differentiated,no lymph node metastasis and TNM stage Ⅰ-Ⅱ were significantly increased(P<0.05).The relative expression level of RMRP in the cells of the si-RMRP group was lower than that of blank and the siRNA-NC group(P<0.001).Compared with the blank group and the siRNA-NC group,the absorbance(A)value of cells at 24,48,72 and 96 h in the si-RMRP group was decreased(P<0.05).The number of invasion cells in the si-RMRP group was lower than that in the blank group and the siRNA-NC group(F=27.765,P<0.001).Conclusions The relative expression levels of RMRP in blood and tissues of NSCLC patients are increased.Down-regulation of the expres-sion of RMRP gene in A549 cells can inhibit cell proliferation and reduce cell invasion.