Background: Influenza A virus (IAV) is a negative-sense RNA virus of the Orthomyxoviridae family and is the etiological agent of a highly contagious acute respiratory disease that can lead to acute lung injury. Objective: To elucidate the molecular mechanisms of IAV infection, an integrative research approach combining gene expression profiling, multinetwork analysis, and in vivo experimental validations was employed. Methods: First, a series of network-based analyses were performed, including protein-protein interaction network construction, weighted gene co-expression network analysis, and subsequent gene set enrichment analysis, to identify the major underlying mechanisms of IAV infection. Following gene expression analysis, core targets, both direct and indirect regulators, were screened. An IAV (H1N1) strain A/PR/8/34-induced acute lung injury mouse model was constructed for in vivo validations. Batch one included two groups to evaluate findings from the multi-network analysis: Mock (n = 10; 5 males and 5 females) and IAV (n = 10; 5 males and 5 females). Batch two included three groups to assess the role of toll-like receptor 3 (TLR3) in IAV infection: Mock (n = 6; 3 males and 3 females), IAV (n = 6; 3 males and 3 females), and TLR3 inhibitor (n = 6; 3 males and 3 females). Body weight was measured on days 0, 3, and 5 after infection. On day 5, lung tissues were collected to assess viral load and histopathological changes. Key targets were examined using enzyme-linked immunosorbent assay, Western blotting, and immunofluorescence staining, both in sera and lung tissues. Results: IAV infection was significantly associated with dysregulation of the immune-inflammation system, such as the LTR, nucle-otide-binding oligomerization domain-(NOD) like receptor, retinoic acid-inducible gene I-like receptor, and nuclear factor kappa-B signaling pathways. Gene set enrichment analysis further indicated that the TLR and necroptosis signaling pathways played crucial roles in the progression of IAV infection (TLR signaling pathway normalized enrichment score = 2.3941, P = 1.00 × 10 ⁻¹⁰; necroptosis normalized enrichment score = 1.9421, P = 6.21 × 10 ⁻⁷). Among the core targets, TLR3 and mixed lineage kinase domain-like protein (MLKL) may regulate gene expression at the transcriptional level (all P < 0.05). In vivo validation using an IAV (PR8) infected acute lung injury mouse model demonstrated increased viral load and lung index, alveolar structural damage, and inflammatory cell infiltration. Immunofluorescence staining exhibited large gaps in Lamin B1 staining and breaches in Emerin signals following IAV-PR8 infection. Expression levels of TLR3, p-receptor-interacting serine/threonine-protein kinase 3 (RIPK3)/RIPK3, and p-mixed lineage kinase domain-like protein (MLKL)/MLKL proteins in lung tissues, as well as proinflammatory factors and mediators in sera, were significantly elevated after IAV infection. Moreover, enhanced neutrophil infiltration (myeloperoxidase) and citrullinated histone H3 (a neutrophil extracellular trap-specific marker), both established indicators of neutrophil extracellular trap formation, were observed. Notably, treatment with a TLR3 inhibitor significantly ameliorated IAV-induced acute lung injury by regulating necroptosis-related targets. Conclusion: Our study provides network-based in vivo evidence that TLR3-receptor-interacting serine/threonine-protein kinase 3-MLKL-mediated necroptosis may underlie IAV-induced acute lung injury and could serve as a potential therapeutic target in severe influenza cases.

Diterpenoid ferruginol is a key intermediate in biosynthesis of active ingredients such as tanshinone and carnosic acid.However, the traditional process of obtaining ferruginol from plants is often cumbersome and inefficient. In recent years, the increasingly developing gene editing technology has been gradually applied to the heterologous production of natural products, but the production of ferruginol in microbe is still very low, which has become an obstacle to the efficient biosynthesis of downstream chemicals, such as tanshinone. In this study, miltiradiene was produced by integrating the shortened diterpene synthase fusion protein,and the key genes in the MVA pathway were overexpressed to improve the yield of miltiradiene. Under the shake flask fermentation condition, the yield of miltiradiene reached about(113. 12±17. 4)mg·L~(-1). Subsequently, this study integrated the ferruginol synthase Sm CYP76AH1 and Sm CPR1 to reconstruct the ferruginol pathway and thereby realized the heterologous synthesis of ferruginol in Saccharomyces cerevisiae. The study selected the best ferruginol synthase(Il CYP76AH46) from different plants and optimized the expression of pathway genes through redox partner engineering to increase the yield of ferruginol. By increasing the copy number of diterpene synthase, CYP450, and CPR, the yield of ferruginol reached(370. 39± 21. 65) mg·L~(-1) in the shake flask, which was increased by 21. 57-fold compared with that when the initial ferruginol strain JMLT05 was used. Finally, 1 083. 51 mg·L~(-1) ferruginol was obtained by fed-batch fermentation, which is the highest yield of ferruginol from biosynthesis so far. This study provides not only research ideas for other metabolic engineering but also a platform for the construction of cell factories for downstream products.
Saccharomyces cerevisiae/genetics* ; Diterpenes/metabolism* ; Metabolic Engineering ; Fermentation ; Abietanes

ObjectiveTo identify the active constituents of Kaixuan Jiedu core prescription （KXJD） and investigate its effective components and therapeutic targets in the treatment of common psoriasis. MethodsUltra-performance liquid chromatography-high resolution mass spectrometry （UPLC-Q-TOF MS） was used to identify and analyze the chemical components of KXJD and its blood-entering chemical components. The chemical components of the single decoction were further identified to clarify the source of the chemical components in KXJD. Then， all identified blood-entering compounds were screened for effective active ingredients through the Swiss ADME database. The active ingredient targets of KXJD were searched on the Swiss Target Prediction platform. The targets of common psoriasis were searched in OMIM， GEO， GeneCards， and DISGNET databases to obtain drug-disease intersection targets. The protein-protein interaction network of intersection targets was constructed using STRING， and then the core blood-entering component-intersection target network of KXJD was constructed. The core target proteins in the network were selected for molecular docking with the core components of KXJD. Small molecules and proteins were pretreated， and appropriate docking sites were selected. AutoDock Vina software was used for continuous local search and repeated iterations to find molecular docking conformations. PyMOL software and LigPlot+ software were used for analysis and visualization. Subsequently， the verification was carried out through animal experiments. SPF-grade male C57 mice were randomly divided into a blank group， a model group， a positive drug methotrexate group， and a KXJD group. In the model group， the methotrexate group， and the KXJD group， imiquimod was applied to the backs of the mice for modeling. The blank group and the model group were administered normal saline by gavage， while the methotrexate group and the KXJD group were respectively administered 1 mg·kg^-1 suspension and 30.42 g·kg^-1 decoction of traditional Chinese medicine by gavage. Five days after administration， the mice were sacrificed， and samples were collected. Hematoxylin-eosin （HE） staining was used to observe the skin tissue samples of mice， and the effect of KXJD on the pathological manifestations of psoriasis mice was analyzed. The expression areas of tumor necrosis factor-α （TNF-α）， cyclooxygenase 2 （PTGS2）， interleukin （IL）-1β， and IL-6 in the skin tissue of mice were detected by immunohistochemistry （IHC）. The mRNA expressions of TNF-α， IL-1β， IL-6， and PTGS2 in the skin tissue of mice were detected by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）. ResultsIn this study， 208 compounds in KXJD were identified by UPLC-Q-TOF MS， and 44 compounds were detected in serum， including 28 prototype components and 16 metabolites. 12 blood-entering active components were screened， and 1 153 active component targets and 1 076 psoriasis-related targets were identified. Eighty-five targets in the intersection set were drug-disease common targets. PPI network analysis showed that TNF-α， IL-1β， IL-6， PTGS2， and ALB were the key target proteins. The results of molecular docking showed that the binding ability of （+）-hexylphenylglycolic acid to key target proteins such as PTGS2 was stable， and PTGS2 showed high stability with a variety of core compounds. Compared with those in the blank group， the stratum corneum and epidermis in the model group mice were significantly thickened， and the pathological Baker score of the mice's skin in the model group was significantly higher than that of the blank group （P<0.01）. The expression areas of PTGS2， TNF-α， IL-1β， and IL-6 proteins in the skin tissue of the model group mice were significantly increased （P<0.01）， and the expression levels of PTGS2， TNF-α， IL-1β， and IL-6 mRNA in the skin tissue of the model group mice were significantly elevated （P<0.01）. Compared with the model group， the pathological Baker scores of the methotrexate group and the KXJD group were both decreased （P<0.01）， and the expression areas in the skin tissue of the methotrexate group and the KXJD group were significantly reduced （P<0.05， P<0.01）. The expression levels of PTGS2， TNF-α， IL-1β， and IL-6 mRNA in the skin tissue of the methotrexate group and the KXJD group were significantly decreased （P<0.01）. ConclusionKXJD can effectively improve the skin lesions of psoriasis model mice and reduce the expression of TNF-α， IL-1β， IL-6， and PTGS2 in the skin tissue of psoriasis model mice. PTGS2 has a stable binding ability with a variety of compounds in the decoction， which may be a key target for the treatment of psoriasis. The compound （+）-hexylphenylglycolic acid may play a key role.

ObjectiveTo identify the active constituents of Kaixuan Jiedu core prescription （KXJD） and investigate its effective components and therapeutic targets in the treatment of common psoriasis. MethodsUltra-performance liquid chromatography-high resolution mass spectrometry （UPLC-Q-TOF MS） was used to identify and analyze the chemical components of KXJD and its blood-entering chemical components. The chemical components of the single decoction were further identified to clarify the source of the chemical components in KXJD. Then， all identified blood-entering compounds were screened for effective active ingredients through the Swiss ADME database. The active ingredient targets of KXJD were searched on the Swiss Target Prediction platform. The targets of common psoriasis were searched in OMIM， GEO， GeneCards， and DISGNET databases to obtain drug-disease intersection targets. The protein-protein interaction network of intersection targets was constructed using STRING， and then the core blood-entering component-intersection target network of KXJD was constructed. The core target proteins in the network were selected for molecular docking with the core components of KXJD. Small molecules and proteins were pretreated， and appropriate docking sites were selected. AutoDock Vina software was used for continuous local search and repeated iterations to find molecular docking conformations. PyMOL software and LigPlot+ software were used for analysis and visualization. Subsequently， the verification was carried out through animal experiments. SPF-grade male C57 mice were randomly divided into a blank group， a model group， a positive drug methotrexate group， and a KXJD group. In the model group， the methotrexate group， and the KXJD group， imiquimod was applied to the backs of the mice for modeling. The blank group and the model group were administered normal saline by gavage， while the methotrexate group and the KXJD group were respectively administered 1 mg·kg^-1 suspension and 30.42 g·kg^-1 decoction of traditional Chinese medicine by gavage. Five days after administration， the mice were sacrificed， and samples were collected. Hematoxylin-eosin （HE） staining was used to observe the skin tissue samples of mice， and the effect of KXJD on the pathological manifestations of psoriasis mice was analyzed. The expression areas of tumor necrosis factor-α （TNF-α）， cyclooxygenase 2 （PTGS2）， interleukin （IL）-1β， and IL-6 in the skin tissue of mice were detected by immunohistochemistry （IHC）. The mRNA expressions of TNF-α， IL-1β， IL-6， and PTGS2 in the skin tissue of mice were detected by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR）. ResultsIn this study， 208 compounds in KXJD were identified by UPLC-Q-TOF MS， and 44 compounds were detected in serum， including 28 prototype components and 16 metabolites. 12 blood-entering active components were screened， and 1 153 active component targets and 1 076 psoriasis-related targets were identified. Eighty-five targets in the intersection set were drug-disease common targets. PPI network analysis showed that TNF-α， IL-1β， IL-6， PTGS2， and ALB were the key target proteins. The results of molecular docking showed that the binding ability of （+）-hexylphenylglycolic acid to key target proteins such as PTGS2 was stable， and PTGS2 showed high stability with a variety of core compounds. Compared with those in the blank group， the stratum corneum and epidermis in the model group mice were significantly thickened， and the pathological Baker score of the mice's skin in the model group was significantly higher than that of the blank group （P<0.01）. The expression areas of PTGS2， TNF-α， IL-1β， and IL-6 proteins in the skin tissue of the model group mice were significantly increased （P<0.01）， and the expression levels of PTGS2， TNF-α， IL-1β， and IL-6 mRNA in the skin tissue of the model group mice were significantly elevated （P<0.01）. Compared with the model group， the pathological Baker scores of the methotrexate group and the KXJD group were both decreased （P<0.01）， and the expression areas in the skin tissue of the methotrexate group and the KXJD group were significantly reduced （P<0.05， P<0.01）. The expression levels of PTGS2， TNF-α， IL-1β， and IL-6 mRNA in the skin tissue of the methotrexate group and the KXJD group were significantly decreased （P<0.01）. ConclusionKXJD can effectively improve the skin lesions of psoriasis model mice and reduce the expression of TNF-α， IL-1β， IL-6， and PTGS2 in the skin tissue of psoriasis model mice. PTGS2 has a stable binding ability with a variety of compounds in the decoction， which may be a key target for the treatment of psoriasis. The compound （+）-hexylphenylglycolic acid may play a key role.

ObjectiveTo systematically explore the underlying mechanisms of Huashi Baidu prescription （HBP） against myocardial injury through a multidimensional network analysis of "transcriptome-putative target-phenotype gene". MethodPutative targets of compounds in HBP were predicted using the Encyclopedia of Traditional Chinese Medicine （ETCM 2.0，http：//www.tcmip.cn/ETCM2/front/） and the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP v2.0，http：//www.tcmip.cn/TCMIP/index.php/Home/Login/login.html）. Clinical predominant symptom phenotypes for HBP against coronavirus disease 2019 （COVID-19） were collected from CNKI and PubMed databases， while clinical side effects of doxorubicin were gathered from the CTD database. Phenotype-related genes were collected from the HPO database and SoFDA data platform （http：//www.tcmip.cn/Syndrome/front/#/）. An interaction network of "transcriptome-putative target-phenotype gene" was constructed. Key nodes were identified through topological feature calculations， and functional enrichment analysis was conducted to explain the underlying mechanism. Pharmacodynamic evaluation and mechanism verification were performed using a doxorubicin-induced myocardial injury mouse model. Sixty-five SPF-grade C57BL/6J male mice were randomly divided into a control group， a doxorubicin model group， and low-， medium-， and high-dose HBP groups （HBP-L/M/H）， with 13 mice per group. Histopathological severity was assessed using hematoxylin-eosin （HE） and Masson staining. Fibrosis markers were measured by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and protein expression was detected by Western blot. ResultA total of 1 044 putative targets for HBP were obtained from ETCM 2.0 and TCMIP v2.0. From the CTD， HPO， and SoFDA databases， 1 223 potential effect-related targets were identified. Cardiac transcriptome sequencing （RNA-seq） yielded 214 genes related to doxorubicin-induced myocardial injury and 58 genes associated with the effects of HBP， using criteria of P-value<0.05 and FC > 1.5/< 0.667. Analysis of the multidimensional molecular network revealed that the mechanisms of HBP on myocardial injury were mainly related to immune-inflammation imbalance， cellular metabolism， myocardial cell function and fibrosis， angiogenesis， contraction and platelet activation， DNA synthesis， metabolism and repair， as well as cell death and oxidative stress. HBP improved cardiovascular abnormalities such as reduced ejection fraction， myocardial fibrosis， myocarditis， hypertriglyceridemia， and arterial/venous thrombosis. Animal experiments demonstrated that HBP reduced the abnormal high expression of Nod-like receptor heat protein domain Protein 3 （NLRP3）， Caspase-1， apoptosis-associated speck-like protein （ASC）， and Gasdermin D （GSDMD） in myocardial tissue induced by doxorubicin （P<0.05）， and improved the elevated mRNA levels of fibrosis markers transforming growth factor-β₁ （TGF-β₁）， Smad3， and α-smooth muscle actin （α-SMA） （P<0.05）. ConclusionHBP can improve myocardial injury through multiple components， targets， and effects， with the inhibition of the NLRP3 inflammasome activation pathway being a key pharmacodynamic mechanism. This study is expected to provide new insights for the development of targeted therapeutic drugs.

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]

The incidence of intrahepatic cholangiocarcinoma (ICC) continues to rise, and there are no effective drugs to treat it. The immune microenvironment plays an important role in the development of ICC and is currently a research hotspot. Icaritin (ICA) is an innovative traditional Chinese medicine for the treatment of advanced hepatocellular carcinoma. It is considered to have potential immunoregulatory and anti-tumor effects, which is potentially consistent with the understanding of "Fuzheng" in the treatment of tumor in traditional Chinese medicine. However, whether ICA can be used to treat ICC has not been reported. Therefore, in this study, sgp19/kRas, an in situ ICC mouse model with intact immune system, was selected to evaluate the efficacy of ICA in the treatment of ICC in vivo for the first time, and the effects of ICA on the tumor immune microenvironment of ICC mice were analyzed by flow cytometry. This experiment was approved by the Experimental Animal Ethics Committee of Capital Medical University (approval number: AEEI-2023-138). In this study, sgp19/kRas ICC mouse model was treated with oral gavage of 100 mg·kg^-1 ICA. We found that ICA significantly inhibited tumor growth and tumor cell proliferation in the sgp19/kRas ICC mouse model after 3 weeks of treatment. Flow cytometry analysis indicated that ICA treatment markedly reduced the proportion of M2 macrophages and increased the number of CD3⁺CD4⁺ T cells. In vitro experiments demonstrated that ICA promoted macrophage polarization towards the M1 phenotype while inhibiting polarization towards the M2 phenotype. Furthermore, transcriptomic analysis suggested that ICA enhanced Toll-like receptor 9 (TLR9) expression, influencing macrophage nitric oxide metabolism synthesis pathways and receptor-related activities, thereby regulating macrophage polarization. In summary, this study demonstrates that ICA treatment significantly delays tumor progression in sgp19/kRas ICC mouse models. Mechanistically, ICA may achieve its anti-ICC effects by upregulating TLR9 receptor expression levels, promoting macrophage polarization towards the M1 phenotype, and altering the tumor immune microenvironment.

Background: Acute respiratory distress syndrome induced by acute lung injury (ALI) is the main cause for the high mortality of corona-virus disease 2019 (COVID-19). Huashi Baidu formula (HSBD) with the effects of eliminating dampness, clearing heat, ventilating lung, and removing toxin has been proven to be effective in the treatment of COVID-19, especially in severe cases. However, the underlying mechanism and target proteins of HSBD remain unclear. Objective: To provide evidence and decipher the mechanism of HSBD in alleviating inflammation and ALI. Materials and methods: A mouse model of ALI was induced by lipopolysaccharide (LPS), and hematoxylin-eosin staining was used to examine the protective effects of HSBD on the model mice. The cellular thermal shift assay and proteomics analysis were used to predict the target proteins. Furthermore, the A549 cells with peroxiredoxin 5 (PRDX5) knockdown were established to validate the predicted proteins. Results: Huashi Baidu formula treatment mitigated ALI and inflammatory cytokine dysfunction in LPS-induced mice, thus exerting a therapeutic effect on COVID-19. Huashi Baidu formula could serve as a therapeutic agent to alleviate inflammation and lung injury via nuclear factor k B and phosphatidylinositol 3-kinase signaling and interleukin 17 inhibition as well as targeting PRDX5, which could be one of the promising targets for treating inflammation. In the A549 cell line with PRDX5 knockdown (si-PRDX5), the anti-inflammation effects of HSBD, including reversing LPS-induced increase in the nitric oxide level and reduction in the hydrogen peroxide content, were attenuated. Thus, HSBD protected A549 cells from LPS-induced inflammation mainly by targeting PRDX5. Conclusions: Huashi Baidu formula alleviates ALI by targeting nuclear factor κB/phosphatidylinositol 3-kinase and PRDX5, as well as inhibiting the immune response induced by IL-17.

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

On February 2022, WHO released the evidence-based guideline on control and elimination of human schistosomiasis, with aims to guide the elimination of schistosomiasis as a public health problem in disease-endemic countries by 2030 and promote the interruption of schistosomiasis transmission across the world. Based on the One Health concept, six evidence-based recommendations were proposed in this guideline. This article aims to analyze the feasibility of key aspects of this guideline in Chinese national schistosomiasis control program and illustrate the significance to guide the future actions for Chinese national schistosomiasis control program. Currently, the One Health concept has been embodied in the Chinese national schistosomiasis control program. Based on this new WHO guideline, the following recommendations are proposed for the national schistosomiasis control program of China: (1) improving the systematic framework building, facilitating the agreement of the cross-sectoral consensus, and building a high-level leadership group; (2) optimizing the current human and livestock treatments in the national schistosomiasis control program of China; (3) developing highly sensitive and specific diagnostics and the framework for verifying elimination of schistosomiasis; (4) accelerating the progress towards elimination of schistosomiasis and other parasitic diseases through integrating the national control programs for other parasitic diseases.
China/epidemiology* ; Disease Eradication ; Humans ; Public Health ; Schistosomiasis/prevention & control* ; World Health Organization