Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.

Objective To investigate the survival outcome-weighted method,survClust,and apply it to the multi-omics data of gliomas,to identify molecular subtypes of gliomas with significant molecular heterogeneity and prognostic differences.Methods The multi-omics data from the Chinese Glioma Genome Atlas(CGGA)was used for outcome weighted integrated subtyping using the survClust method,and a Cox proportional risk model was fitted to assess the prognosis of patients with different subtypes.Differentially expressed genes(DEmiRNAs,DEmRNAs,DMGs)between different subtypes were screened,and Gene Ontology(GO)analysis was performed for overlapping genes among DEmiRNAs target genes,DEmRNAs,and DMGs.Finally,we performed immune infiltration analysis between different subtypes.Results The patients with gliomas were divided into high-risk and low-risk groups by using survClust,and the risk of death for patients in the high-risk group was 2.931 times higher than in the low-risk group.The distribution of differential genes was significantly different among different subtypes,and 194 DEmiRNAs,3396 DEmRNAs,and 1230 DMGs were screened.189 overlapping genes were used for GO analysis,and 52 GO terms with statistically significant differences were obtained.In addition,the level of immune infiltration differed statistically between the different subtypes in terms of B cells,CD4+T cells,CD8+T cells,neutrophils,macrophages and myeloid dendritic cells.Conclusion The outcome-weighted integration algorithm survClust can effectively identify subtypes of gliomas with both molecular heterogeneity and significant prognostic differences.At the same time,the potential biomarkers screened based on subtypes will provide a scientific and theoretical basis for individualized treatment of gliomas.

Objective:To investigate the diagnosis value of serum levels of soluble B7-H3(sB7-H3),trefoil factor 1(TFF1)and lipocalin-2(LCN-2)in breast cancer(BC)patients.Methods:From March 2020 to March 2023,196 newly diagnosed BC patients accepted by Huanghe San-menxia hospital were regarded as the study subjects and assigned to the BC group;84 patients with benign breast lesions and 76 physically healthy individuals served as the benign lesion group and the control group,respectively;clinical data were collected.ELISA method was applied to de-tect the serum levels of sB7-H3,TFF1,and LCN-2 in each group,and the relationship between the serum levels of the three and the clinical and pathological characteristics of BC patients was analyzed;Spearman method was applied to analyze the correlation between serum sB7-H3,TFF1,LCN-2 levels and clinical pathological characteristics in BC patients;receiver operating characteristic(ROC)curve was plotted to evaluate the diagnostic value of serum sB7-H3,TFF1,and LCN-2 levels for BC.Results:Compared with the reference group,the serum levels of sB7-H3,TFF1,and LCN-2 in the benign lesion group and BC group were obviously increased(P＜0.05),the serum levels of sB7-H3,TFF1,and LCN-2 in the BC group were obviously higher than those in the benign lesion group(P＜0.05);the serum levels of sB7-H3,TFF1,and LCN-2 were obviously elevated in BC patients with tumour diameter＞2 cm,TNM stage Ⅲ+Ⅳ,lymph node metastasis,and negative ER expression(P＜0.05),the serum levels of sB7-H3,TFF1 and LCN-2 were positively correlated with tumor diameter(r=0.463,0.442,0.481,P＜0.001),positive correla-tion with TNM stage(r=0.474,0.394,0.562,P＜0.001),positive correlation with lymph node me-tastasis(r=0.567,0.488,0.409,P＜0.001),and negative correlation with ER expression(r=-0.575,-0.534,-0.538,P＜0.001);the AUC for serum sB7-H3,TFF1,and LCN-2 alone for BC diagnosis were 0.817,0.814,and 0.830,respectively,and the combined diagnosis was superior to the separate diagnosis(AUC=0.911,95％CI:0.871-0.942).Conclusion:The serum levels of sB7-H3,TFF1 and LCN-2 in BC patients were significantly increased,which is of high clinical value for the diagnosis of BC.

According to the requirements of the regulatory authorities, degree of modification (DP) should be included in the characterisation of the PEGylated protein drug substance, and is one of the critical quality attributes for quality control. In this study, based on the fundamental assumption that the refractive index (RI) signal and the ultraviolet (UV) signal of PEGylated protein are equal to the sum of the corresponding signal produced by the polyethylene glycol (PEG) and protein parts of the conjugates in their uncoupled state, we developed a method to determine the DP of PEGylated recombinant human growth hormone (inpegsomatropin). In this method, 20 μL of 1 mg·mL^-1 human growth hormone (hGH) standard, 2 mg·mL^-1 PEG reference substance and 1 mg·mL^-1 drug substance solution were each injected to size exclusion chromatographic (SEC) column for separation, detected with ultraviolet and refractive index (UV-RI) detectors in series. Finally, the DP was calculated as the formula derived from the fundamental assumption. The developed SEC-UV-RI method showed good specificity, repeatability (RSD = 0.63%, n = 9) and accuracy, with a recovery of 100.0%, compared with the result obtained from the simultaneously established classical acid hydrolysis method, demonstrating pretty handleability and accessibility, and is appropriate for quality control test of DP for this drug substance.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Objective:To investigate the malignant potential of histopathological class B3 and B5a lesions by ultrasound-guided core needle biopsy (CNB).Methods:Retrospective analysis of the histopathological results of 712 breast lesions that successively underwent CNB process and surgical resection in the Shanghai General Hospital from January 2018 to December 2022, of which 47 lesions were reported as class B3 and 70 lesions as class B5a.Results:CNB identified 47 category B3 lesions, comprising 19 cases of atypical ductal hyperplasia, 17 papillary lesions, 8 phyllodes tumors, and 3 complex sclerosing lesions. Of these cases, surgical pathology was in full agreement with CNB pathology in 27 instances, indicating a concordance rate of 57.4% (27/47) and an inconsistency rate of 42.6% (20/47). Out of the 20 inconsistent cases, 70.0% (14/20) were upgraded based on the findings from the surgical pathology.Specifically, 4 cases of atypical ductal hyperplasia and 2 cases of intraductal papilloma were upgraded to invasive breast cancer (B5b) after surgery. Among the 4 cases with puncture pathology indicating atypical ductal hyperplasia and one complex sclerosing lesion, these five lesions were upgraded to ductal carcinoma in situ (B5a) after surgery. Two puncture pathologies were diagnosed as atypical ductal hyperplasia, and these were upgraded to ductal carcinoma in situ with microinvasion (B5b) after surgery. One puncture pathology indicated a borderline phyllodes tumor, and this was upgraded to malignant phyllodes tumor (B5b) after surgery. And 30.0% (6/20) resulted in downgrade after surgery, specifically 4 cases of atypical ductal hyperplasia, which were downgraded to breast adenopathy (B2). Of these, 1 puncture pathology was identified as atypical ductal hyperplasia and one as a borderline phyllodes tumor, which were both downgraded to fibroadenoma (B2). Seventy lesions were diagnosed as B5a lesions by CNB pathology, with 28 of them showing complete concurrence with the surgical pathology, a concordance rate of 40.0% (28/70), and an inconsistency rate of 60.0% (42/70). Of the 42 cases with discrepancies, all 42 were upgraded, yielding an upgrading rate of 100% (42/42). Of these, 21 were upgraded to ductal carcinoma in situ with microinvasion (B5b) and 21 to invasive breast cancer (B5b).Conclusions:Lesions with CNB pathology in categories B3 and B5a have a high rate of postoperative escalation. B3 and B5a lesions should be treated with considerable care, especially atypical ductal hyperplasia, which should be surgically resected, and CNB examination should be performed twice if necessary.

Objective:To investigate the efficacy and safety of comprehensive therapy in the treatment of advanced unresectable hepatocellular carcinoma.Methods:Clinical data of 34 patients with primary liver cancer admitted to Peking Union Medical College Hospital from Nov 2018 to Dec 2020 initially evaluated as unresectable were treated firstly by combined therapy and then underwent reevaluation for further management.Results:A total of 34 patients completed the integrative treatment, and no serious adverse events occurred. Among them, 6 patients were evaluated as partial remission, and underwent successful tumor resection, tumors in 7 patients were stable, and 21 patients suffered from disease progression.Conclusion:After comprehensive therapy, unresectable tumors in some patients could reduce and be rendered resection.

Objective:To investigate the characteristics of death, tendency and the prediction of Shenzhen residents with adult hematological malignancies from 2017 to 2020.Methods:The surveillance data of hematological malignancies from 2017 to 2020 and the demographic data in Shenzhen were collected from Shenzhen death cause monitoring system and Shenzhen Center for Disease Control and Prevention, respectively. The data of the 7th national demographic data in 2020 were set as the standardized population data. Crude mortality rate (CMR), standardized mortality rate (SMR) and annual percentage change (APC) of mortality were calculated by using Joinpoint software. The grey model GM(1,1) was built to predict the mortality of adult hematological malignancies in Shenzhen between 2021 and 2025.Results:From 2017 to 2022, the male CMR of hematological malignancies was 1.15/100 000 to 1.85/100 000, and the SMR was 2.24/100 000 to 2.44/100 000; the female CMR of hematological malignancies was 0.81/100 000 to 1.75/100 000, and the SMR was 1.67/100 000 to 1.90/100 000. There were no statistically significant differences in the annual CMR and SMR between male and female hematological malignancies (all P > 0.05), and the annual change trend of CMR and SMR was not significant. The APC of male and female CMR was 27.28% and 12.70%, respectively (χ 2 = 0.01, P = 0.939); the APC of male and female SMR was 1.12% and 4.77%, respectively (χ 2 = 0.91, P = 0.318). The death causes of hematological malignancies were successively acute myeloid leukemia (AML), lymphoma, multiple myeloma, acute lymphoblastic leukemia (ALL), myelodysplastic syndrome (MDS) plus chronic myelomonocytic leukemia (CMML), chronic lymphoblastic leukemia (CLL) plus chronic myelogenous leukemia (CML). The CMR of patients with hematological malignancies aged 18-40 years was low, the CMR began to rise in patients above 40 years, especially the rapid increase at the age of 60 years, reaching the peak at the age of 80 years or above. The shortest median time of all kinds of hematological malignancies from the onset of disease to the death was found in AML group (8 months, range 0.1-168 months), the longest time was in CLL+CML group (24 months, range 0.1-300 months). Infection was the most direct cause of death, followed by single organ failure. GM(1,1) model had the better predictive effects and the total SMR would increase from 2021 to 2025 (4.52/100 000, 4.76/100 000, 5.01/100 000, 5.28/100 000 and 5.57/100 000, respectively). Conclusions:The incidence of hematological malignancies in Shenzhen residents over 40 years old is on the increase. The trend of adult hematological malignancies in Shenzhen will rise predicted by GM (1,1) grey model.

Ankle Fractures ; Femoral Fractures ; Fracture Fixation, Internal ; Humans ; Patella/surgery* ; Patellar Dislocation/surgery*