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]

OBJECTIVE: To explore the efficacy of venetoclax (VEN) plus azacitidine (AZA) in patients with FLT3-ITD mutated relapsed/refractory acute myeloid leukemia (FLT3-ITD^mut R/R AML) and analyze the molecular genetic characteristics of the patients. METHODS: Clinical baseline characteristics and follow-up data of 16 R/R AML patients treatd with VEN plus AZA in the hematology department of Shenzhen Second People's Hospital from November 2018 to April 2021 were collected. Leukemia related genes were detected by next-generation sequencing(NGS) or PCR. The relationship between the efficacy of VEN plus AZA and molecular genetics characteristics of patients with FLT3-ITD^mut R/R AML were analyzed. RESULTS: 14.3% (1/7) of the patients in FLT3-ITD^mut group and 22.2% (2/9) of the patients in FLT3-ITD^wt group achieved complete remission (CR)/CR with incomplete blood count recovery (CRi), respectively, with no significant difference (P=0.69). There was no significant difference in overall response rate (ORR) (CR/CRi+PR) between FLT3-ITD^mut group and FLT3-ITD^wt group [42.9%(3/7) vs 44.4%(4/9), P=0.95], too. The median overall survival (OS) time of FLT3-ITD^mut patients was significantly shorter than that of FLT3-ITD^wt patients (130 vs 300 days, respectively) (P =0.02). Co-existing mutations of FLT3-ITD and IDH1 were detected in one patient who achieved CR. Co-existing mutations of FLT3-ITD and SF3B1 were found in one patient who achieved PR. Three FLT3-ITD^mut R/R AML patients accompanied with NPM1 mutation had no response to VEN plus AZA. CONCLUSION VEN plus AZA showed a certain effect on patients with FLT3-ITD^mut R/R AML. To improve OS of the patients, bridging transplantation is need. IDH1 and SF3B1 mutations might predict that patients with FLT3-ITD^mut R/R AML have treatment response to VEN plus AZA, while the combination of NPM1 mutation may indicate poor response.
Humans ; Nucleophosmin ; Prognosis ; Leukemia, Myeloid, Acute/genetics* ; Mutation ; Azacitidine/therapeutic use* ; fms-Like Tyrosine Kinase 3/genetics*

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 efficacy of liposomal doxorubicin intensive preconditioning regimen and allogeneic hematopoietic stem cell transplantation (allo-HSCT) in treatment of leukemia.Methods:The data of 20 patients with intensive preconditioning regimen allo-HSCT who were admitted to Shenzhen Second People's Hospital from January 2016 to June 2017 were retrospectively analyzed. The transplantation effect, occurrence of complications and prognosis of patients were analyzed.Results:The median time of granulocyte engraftment was 17 d (13-23 d); the median time of platelet engraftment was 22.5 d (minimum 13 d, maximum >90 d). The acute graft-versus-host disease (GVHD) and chronic GVHD occurred in 2 cases and 1 case, respectively. Eight cases occurred hemorrhagic cystitis, 15 cases occurred Epstein-Barr viremia, 8 cases occurred cytomegaloviremia, 1 case occurred sepsis, 1 case occurred acute liver injury, and 2 cases occurred fungal pneumonia. The median follow-up time was 31.7 months (0.8-53.8 months). One patient died of intracranial infection on the 25th day after transplantation; 3 patients relapsed during the follow-up period, and 2 of them died; the other 16 patients carried 100% donor genes during the follow-up period.Conclusions:The liposomal doxorubicin intensive preconditioning regimen and allo-HSCT have a good effect on leukemia. Increasing the intensity of pretreatment does not increase the treatment-related adverse reactions. The incidence rates of Epstein-Barr viremia and cytomegaloviremia are high, but they are improved after active treatment.

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

Objective:To evaluate the efficacy and safety of azacitidine combined with HAG regimen in the treatment of newly diagnosed elderly acute myeloid leukemia (AML) patients ineligible for intensive chemotherapy.Methods:Eighteen newly diagnosed elderly AML patients ineligible for intensive chemotherapy from July 2019 to September 2021 in the Second People's Hospital of Shenzhen were prospectively enrolled in this study. They were non-randomly divided into azacitidine combined with HAG regimen (AZA-HAG) group (9 cases) and decitabine combined with HAG regimen (DEC-HAG) group (9 cases). The primary endpoint of the study was overall response [complete remission (CR)+partial remission], and the secondary endpoints included CR + complete remission with incomplete count recovery (CRi), overall survival (OS) and drug safety. Kaplan-Meier method was used to analyze the OS.Results:The median age of 18 patients was 67 years old (60-77 years old) , and 8 of them were in high-risk group. After one course of treatment, the overall response and CR+CRi were observed in 7 of 9 patients in AZA-HAG group, and they were observed in 8 of 9 patients in DEC-HAG group, and there was no significant difference between the two groups (both P = 1.000). The median duration of CR+CRi was 7 months in both groups, and the median OS time was 12 months in both groups; there was no significant difference in OS between the two groups ( χ2 = 0.02, P = 0.895). In AZA-HAG group, 1 patient with TP53 mutation and 1 patient with ASXL1+RUNX1 mutation acquired CR, and 1 patient with NPM1 wild-type combined with FLT3-ITD and ASXL1 mutation did not respond. There was no significant difference in the incidence of grade 3-4 hematological adverse reactions between the two groups (all P < 0.05). Conclusions:Azacitidine combined with low-dose HAG regimen in the treatment of newly diagnosed elderly AML patients ineligible for intensive chemotherapy has satisfactory efficacy and long-term survival, and the adverse reactions can be tolerated.

Objective:To investigate the therapeutic effect of venetoclax combined with azacitidine in treatment of myelodysplastic syndromes (MDS) complicated with monoclonal globulinemia of unknown significance (MGUS).Methods:The clinical data of a patient with MDS complicated with MGUS in the Second People's Hospital of Shenzhen in December 2020 were retrospectively analyzed, and the literatures were reviewed.Results:According to results of bone marrow smear, cytogenetics, and next-generation sequencing, the patient was diagnosed as MDS and MGUS complicated with ASXL1, RUNX1, EZH2, STAG2 mutations as well as t(11;14). No response was observed after 2 courses of azacitidine and 1 course of azacitidine plus HAG. Later the patient achieved complete remission and negative RUNX1 and STAG2 mutations after a course of venetoclax combined with azacitidine. Meanwhile, M protein exhibited a decrease more than 50%. To date, the patient was still in complete remission.Conclusions:The regimen of venetoclax combined with azacitidine shows a significant efficacy and good tolerance to patient with co-occurrence of MDS and MGUS with t(11; 14).

Objective: Moxifloxacin (MFX) shows good activity against and can be a possible antibiotic therapy to treat infection; however, other studies have shown a lower or no activity. We aimed to evaluate MFX activity against using zebrafish (ZF) model . Methods: A formulation of labeled with CM-Dil was micro-injected into ZF. Survival curves were determined by recording dead ZF every day. ZF were lysed, and colony-forming units (CFUs) were enumerated. Bacteria dissemination and fluorescence intensity in ZF were analyzed. Inhibition rates of MFX and azithromycin (AZM, positive control) were determined and compared. Results: Significantly increased survival rate was observed with different AZM concentrations. However, increasing MFX concentration did not result in a significant decrease in ZF survival curve. No significant differences in bacterial burdens by CFU loads were observed between AZM and MFX groups at various concentrations. Bacterial fluorescence intensity in ZF was significantly correlated with AZM concentration. However, with increasing MFX concentration, fluorescence intensity decreased slightly when observed under fluorescence microscope. Transferring rates at various concentrations were comparable between the MFX and AZM groups, with no significant difference. Conclusion MFX showed limited efficacy against using ZF model. Its activity needs to be confirmed.
Animals ; Anti-Bacterial Agents ; pharmacology ; Disease Models, Animal ; Moxifloxacin ; pharmacology ; Mycobacterium Infections, Nontuberculous ; drug therapy ; Mycobacterium abscessus ; drug effects ; Zebrafish

Momordicae Semen a traditional toxic Chinese medicine, which was first recorded in Kaibao Bencao of the Northern Song Dynasty. It has the effects in reducing swelling, dispersing knot, and attacking sores. It is mainly distributed in South China, such as Guangxi and Guangdong. It is also distributed in Southeast Asian countries, such as Thailand and Vietnam. The present study showed abundant chemical components extracted from Momordicae Semen, including steroids, sterols, volatile oils and fatty acids. Among them, 30 terpenoids, 102 compounds in volatile oil, 6 sterols and 19 fatty acids have been identified. Aqueous extracts and alcohol extracts of Momordicae Semen have the toxicity, and the toxicity decreases with the increase of oil content. The main toxic components reported in the literatures are cochinchinin and saponins. Pharmacological studies have shown that in addition to its traditional anti-cancer, anti-inflammatory, antibacterial and other pharmacological effects, Momordicae Semen also exhibited many pharmacological effects, such as anti-ulcer, anti-oxidation and immune regulation. In recent years, there have been increasingly more research reports on Momordicae Semen. By studying relevant domestic and foreign literatures from 1964 to 2019 in China National Knowledge Infrastructure, Wanfang, PubMed and Web of Science, chemical constituents, pharmacological effects and toxicological research of Momordicae Semen were summarized, which will provide reference for further research and application of Momordicae Semen in the future.

PURPOSE: We aim to examine nasopharyngeal carcinoma (NPC) characteristics and survival outcomes in patients aged 70 years and older in the intensity-modulated radiotherapy (IMRT) era. MATERIALS AND METHODS: From 2006 to 2013, 126 non-metastatic NPC patients aged ≥ 70 years who were treated with IMRT +/‒ chemotherapy were included. Adult Comorbidity Evaluation 27 (ACE-27) was used to measure patient comorbidities. The overall survival (OS) and cancer-specific survival (CSS)were calculatedwith the Kaplan-Meier method, and differenceswere compared using the log-rank test. The Cox proportional hazards model was used to carry out multivariate analyses. RESULTS: For the entire group, only two patients (1.6%) presented stage I disease, and up to 84.1% patients had stage III-IVB disease. All patients had a comorbidity score of 0 in 24 (19.0%), 1 in 45 (35.7%), 2 in 42 (33.3%), and 3 in 15 (11.9%) patients. The main acute grade during radiotherapy was 3-4 adverse events consisting of mucositis (25.4%), bone marrow suppression (16.7%), and dermatitis (8.7%). After treatment, four patients (3.2%) developed temporal lobe injury. Five-year CSS and OS rates were 67.3% (95% confidence interval [CI], 58.6% to 77.4%) and 54.0% (95% CI, 45.6% to 63.9%), respectively. Five-year OS was significantly higher for ACE-27 score 0-1 than ACE-27 score 2-3 (72.9% and 39.9%, respectively; p < 0.001). Multivariate analyses showed ACE-27 score 0-1 was significantly associated with superior OS (hazard ratio [HR], 3.02; 95% CI, 1.64 to 5.55; p < 0.001). In addition, the rate of OS was higher for stage I-III than that of stage IV, with borderline significance (HR, 1.67; 95% CI, 0.99 to 2.82; p=0.053). But no significant advantage was observed in OS when chemotherapy was used (p > 0.05). CONCLUSION: Our findings suggest IMRT +/– chemotherapy has a manageable toxicity and provides an acceptable survival in patients aged ≥ 70 years with NPC. ACE-27 score was significantly associated with survival outcomes in this group population.
Adult ; Bone Marrow ; Comorbidity ; Dermatitis ; Drug Therapy ; Humans ; Methods ; Mucositis ; Multivariate Analysis ; Proportional Hazards Models ; Radiotherapy ; Radiotherapy, Intensity-Modulated* ; Temporal Lobe