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 molecular features of chronic myelomonocytic leukemia (CMML) . Methods: According to 2022 World Health Organization (WHO 2022) classification, 113 CMML patients and 840 myelodysplastic syndrome (MDS) patients from March 2016 to October 2021 were reclassified, and the clinical and molecular features of CMML patients were analyzed. Results: Among 113 CMML patients, 23 (20.4%) were re-diagnosed as acute myeloid leukemia (AML), including 18 AML with NPM1 mutation, 3 AML with KMT2A rearrangement, and 2 AML with MECOM rearrangement. The remaining 90 patients met the WHO 2022 CMML criteria. In addition, 19 of 840 (2.3%) MDS patients met the WHO 2022 CMML criteria. At least one gene mutation was detected in 99% of CMML patients, and the median number of mutations was 4. The genes with mutation frequency ≥ 10% were: ASXL1 (48%), NRAS (34%), RUNX1 (33%), TET2 (28%), U2AF1 (23%), SRSF2 (21.1%), SETBP1 (20%), KRAS (17%), CBL (15.6%) and DNMT3A (11%). Paired analysis showed that SRSF2 was frequently co-mutated with ASXL1 (OR=4.129, 95% CI 1.481-11.510, Q=0.007) and TET2 (OR=5.276, 95% CI 1.979-14.065, Q=0.001). SRSF2 and TET2 frequently occurred in elderly (≥60 years) patients with myeloproliferative CMML (MP-CMML). U2AF1 mutations were often mutually exclusive with TET2 (OR=0.174, 95% CI 0.038-0.791, Q=0.024), and were common in younger (<60 years) patients with myelodysplastic CMML (MD-CMML). Compared with patients with absolute monocyte count (AMoC) ≥1×10(9)/L and <1×10(9)/L, the former had a higher median age of onset (60 years old vs 47 years old, P<0.001), white blood cell count (15.9×10(9)/L vs 4.4×10(9)/L, P<0.001), proportion of monocytes (21.5% vs 15%, P=0.001), and hemoglobin level (86 g/L vs 74 g/L, P=0.014). TET2 mutations (P=0.021) and SRSF2 mutations (P=0.011) were more common in patients with AMoC≥1×10(9)/L, whereas U2AF1 mutations (P<0.001) were more common in patients with AMoC<1×10(9)/L. There was no significant difference in the frequency of other gene mutations between the two groups. Conclusion: According to WHO 2022 classification, nearly 20% of CMML patients had AMoC<1×10(9)/L at the time of diagnosis, and MD-CMML and MP-CMML had different molecular features.
Humans ; Aged ; Middle Aged ; Leukemia, Myelomonocytic, Chronic/genetics* ; Prognosis ; Splicing Factor U2AF/genetics* ; Mutation ; Myelodysplastic Syndromes/genetics* ; Leukemia, Myeloid, Acute/genetics*

Gut dysbiosis,a well-known risk factor to triggers the progression of Alzheimer's disease(AD),is strongly associated with metabolic disturbance.Trimethylamine N-oxide(TMAO),produced in the dietary choline metabolism,has been found to accelerate neurodegeneration in AD pathology.In this study,the cognitive function and gut microbiota of TgCRND8(Tg)mice of different ages were evaluated by Morris water maze task(MWMT)and 16S rRNA sequencing,respectively.Young pseudo germ-free(PGF)Tg mice that received faecal microbiota transplants from aged Tg mice and wild-type(WT)mice were selected to determine the role of the gut microbiota in the process of neuropathology.Excessive choline treatment for Tg mice was used to investigate the role of abnormal choline metabolism on the cognitive functions.Our results showed that gut dysbiosis,neuroinflammation response,Aβ deposition,tau hyper-phosphorylation,TMAO overproduction and cyclin-dependent kinase 5(CDK5)/transcription 3(STAT3)activation occurred in Tg mice age-dependently.Disordered microbiota of aged Tg mice accelerated AD pathology in young Tg mice,with the activation of CDK5/STAT3 signaling in the brains.On the contrary,faecal microbiota transplantation from WT mice alleviated the cognitive deficits,attenuated neuro-inflammation,Aβ deposition,tau hyperphosphorylation,TMAO overproduction and suppressed CDK5/STAT3 pathway activation in Tg mice.Moreover,excessive choline treatment was also shown to aggravate the cognitive deficits,Aβ deposition,neuroinflammation and CDK5/STAT3 pathway activation.These findings provide a novel insight into the interaction between gut dysbiosis and AD progression,clarifying the important roles of gut microbiota-derived substances such as TMAO in AD neuropathology.

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 explore the expression levels and clinical significance of helper T cell 1/helper T cell 2 (Th1/Th2) cytokine and interleukin-6 (IL-6) in patients with acute leukemia (AL) complicated by infection. METHODS: 68 patients with AL complicated by infection admitted to Wuhan Fifth Hospital from May 2017 to January 2020 were enrolled as study group, 50 AL patients without infection were enrolled as AL group, and 30 healthy volunteers checked in physical examination center were enrolled as healthy control group. The levels of serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10), and peripheral blood Th1/Th2 cells subsets were measured and compared among the three groups. The serum IL-6, IL-10, TNF-α and Th1/Th2 were compared between the patients with mild to moderate infection (n=52) and septic shock (n=16). The relationship between IL-6, IL-10, TNF-α, Th1/Th2 and AL infection was analyzed. RESULTS: The levels of IL-6, IL-10 , TNF-α, and the proportion of Th2 of the patients in study group and AL group were significantly higher than those in healthy control group (P<0.001), while the proportion of Th1 and Th1/Th2 were significantly lower than those in healthy control group (P<0.001). The levels of IL-6, IL-10 and TNF-α, and the proportion of Th2 the patients in study group were significantly higher than those in AL group (P<0.001), while the proportion of Th1 and Th1/Th2 were significantly lower than those in AL group (P<0.001). The serum IL-6, IL-10 and TNF-α level of the patients in septic shock group were significantly higher than those in mild-to-moderate infection group (P<0.001), while Th1/Th2 was lower than those in mild-to-moderate infection group (P<0.001). The results of ROC curve analysis showed that the area under the ROC curve (AUC) values of IL-6, IL-10, TNF-α and Th1/Th2 alone for the diagnosis of septic shock were 0.779, 0.761, 0.724 and 0.718, which were lower than that their combination (0.910) (P<0.05). CONCLUSION The levels of serum IL-6, IL-10 and TNF-α are high in patients with AL complicated infection and septic shock, while Th1/Th2 cell subsets is low. The combined detection of serum IL-6, IL-10, TNF-α and Th1/Th2 is a good diagnostic value for predicting the occurrence of severe septic shock.
Cytokines/metabolism* ; Humans ; Interleukin-10 ; Interleukin-6/metabolism* ; Leukemia/metabolism* ; Shock, Septic/metabolism* ; Th1 Cells/metabolism* ; Th2 Cells/metabolism* ; Tumor Necrosis Factor-alpha/metabolism*

OBJECTIVE: Aeromonas has recently been recognized as an emerging human pathogen. Aeromonas-associated diarrhea is a phenomenon occurring worldwide. This study was designed to determine the prevalence, genetic diversity, antibiotic resistance, and pathogenicity of Aeromonas strains isolated from food products in Shanghai. METHODS: Aeromonas isolates ( n = 79) collected from food samples were analyzed using concatenated gyrB- cpn60 sequencing. The antibiotic resistance of these isolates was determined using antimicrobial susceptibility testing. Pathogenicity was assessed using β-hemolytic, extracellular protease, virulence gene detection, C. elegans liquid toxicity (LT), and cytotoxicity assays. RESULTS: Eight different species were identified among the 79 isolates. The most prevalent Aeromonas species were A. veronii [62 (78.5%)], A. caviae [6 (7.6%)], A. dhakensis [3 (3.8%)], and A. salmonicida [3 (3.8%)]. The Aeromonas isolates were divided into 73 sequence types (STs), of which 65 were novel. The isolates were hemolytic (45.6%) and protease-positive (81.0%). The most prevalent virulence genes were act (73.4%), fla (69.6%), aexT (36.7%), and ascV (30.4%). The results of C. elegans LT and cytotoxicity assays revealed that A. dhakensis and A. hydrophila were more virulent than A. veronii, A. caviae, and A. bivalvium. Antibiotic resistance genes [ tetE, blaTEM, tetA, qnrS, aac(6)-Ib, mcr -1, and mcr-3] were detected in the isolates. The multidrug-resistance rate of the Aeromonas isolates was 11.4%, and 93.7% of the Aeromonas isolates were resistant to cefazolin. CONCLUSION The taxonomy, antibiotic resistance, and pathogenicity of different Aeromonas species varied. The Aeromonas isolates A. dhakensis and A. hydrophila were highly pathogenic, indicating that food-derived Aeromonas isolates are potential risks for public health and food safety. The monitoring of food quality and safety will result in better prevention and treatment strategies to control diarrhea illnesses in China.
Aeromonas/genetics* ; Animals ; Anti-Bacterial Agents/pharmacology* ; Caenorhabditis elegans ; Cefazolin ; China/epidemiology* ; Diarrhea ; Drug Resistance, Multiple, Bacterial/genetics* ; Genetic Variation ; Humans ; Peptide Hydrolases/genetics* ; Virulence/genetics*

To comprehensively evaluate the quality of commercial Ginseng Radix et Rhizoma Rubra, 43 batches of commercial Ginseng Radix et Rhizoma Rubra were collected to determine the content of nine ginsenosides Rg_1, Re, Rb_1, Rk_3, Rh_4, 20(S)-Rg_3, 20(R)-Rg_3, Rk_1, and Rg_5 by high performance liquid chromatography(HPLC). The quality of the commercial Ginseng Radix et Rhizoma Rubra was evaluated by correlation analysis, principal component analysis, factor analysis, analysis of variance(ANOVA), and cluster heatmap analysis. The content determination indicated that the content of common ginsenosides in commercial Ginseng Radix et Rhizoma Rubra were higher while that of rare ginsenosides were lower. Multivariate statistical analysis revealed that ginsenosides Rg_1 and Rb_1 were significantly positively correlated with rare ginsenosides, and Rg_1, Rb_1 and rare ginsenosides played an important role in evaluating the quality of commercial Ginseng Radix et Rhizoma Rubra. In combination with the processing principle and current quality situation of Ginseng Radix et Rhizoma Rubra, it is recommended to improve the content limit of Rb_1 in the existing quality standards.
Panax ; Ginsenosides/analysis* ; Rhizome/chemistry* ; Plant Roots/chemistry* ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal

Purpose: The aim of this study was to compare the efficacy of liver transplantation (LT) and liver resection (LR) for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) and to investigate risk factors affecting prognosis. Materials and Methods: A total of 94 HCC patients with PVTT type I (segmental PVTT) and PVTT type II (lobar PVTT) were involved and divided into LR (n=47) and LT groups (n=47). Recurrence-free survival (RFS) and overall survival (OS) were compared before and after inverse probability of treatment weighting (IPTW). Prognostic factors for RFS and OS were explored. Results: Two treatment groups were well-balanced using IPTW. In the entire cohort, LT provided a better prognosis than LR. Among patients with PVTT type I, RFS was better with LT (p=0.039); OS was not different significantly between LT and LR (p=0.093). In subgroup analysis of PVTT type I patients with α-fetoprotein (AFP) levels >200 ng/mL, LT elicited significantly longer median RFS (18.0 months vs. 2.1 months, p=0.022) and relatively longer median OS time (23.6 months vs. 9.8 months, p=0.065). Among patients with PVTT type II, no significant differences in RFS and OS were found between LT and LR (p=0.115 and 0.335, respectively). Multivariate analyses showed treatment allocation (LR), tumor size (>5 cm), AFP and aspartate aminotransferase (AST) levels to be risk factors of RFS and treatment allocation (LR), AFP and AST as risk factors for OS. Conclusion LT appeared to afford a better prognosis for HCC with PVTT type I than LR, especially in patients with AFP levels >200 ng/mL.

Huashi Baidu prescription (HSBDF), recommended in the Guideline for the Diagnosis and Treatment of Novel Coronavirus (2019-nCoV) Pneumonia (On Trials, the Seventh Edition), was clinically used to treat severe corona virus disease 2019 (COVID-19) with cough, blood-stained sputum, inhibited defecation, red tongue etc. symptoms. This study was aimed to elucidate and profile the knowledge on its chemical constituents and the potential anti-inflammatory effect in vitro. In the study, the chemical constituents in extract of HSBDF were characterized by UPLC-Q-TOF/MS in both negative and positive modes, and the pro-inflammatory cytokines were measured by enzyme-linked immunosorbent assays (ELISA) to determine the effects of HSBDF in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The results showed that a total of 217 chemical constituents were tentativedly characterized in HSBDF. Moreover, HSBDF could alleviate the expression levels of IL-6 and TNF-α in the cell models, indicating that the antiviral effects of HSBDF might be associated with regulation of the inflammatory cytokines production in RAW264.7 cells. We hope that the results could be served as the basic data for further study of HSBDF on anti-COVID-19 effect.
Anti-Inflammatory Agents/therapeutic use* ; Antiviral Agents/therapeutic use* ; COVID-19/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Humans ; Plant Extracts/therapeutic use* ; SARS-CoV-2/drug effects*