ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， network pharmacology， molecular docking and cell experiments， the active ingredients， possible targets and molecular mechanisms of Baoxin granules（BXG） regulating ferroptosis in the treatment of heart failure（HF） were explored. MethodsBXG intestinal absorption fluid was prepared by everted gut sac and the chemical composition contained therein were identified by UPLC-Q-TOF-MS. According to the obtained components， the potential targets of BXG were predicted， and the HF-related targets and related genes of ferroptosis were retrieved at the same time， and the intersecting targets were obtained by Venn diagram. In addition， the protein-protein interaction（PPI） network and the component-target network were constructed， and the core components and core targets were obtained by topological analysis. Then Gene Ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis were performed on the core targets， and molecular docking validation of the key targets and main components was carried out by AutoDockTools 1.5.7. H9c2 cells were used to establish a oxygen-glucose deprivation model， and the protective effect of BXG on cells was investigated by detecting cell viability， cell survival rate and reactive oxygen species（ROS） level. The protein expression levels of signal transducer and activator of transcription 3（STAT3）， phosphorylation（p）-STAT3 and glutathione peroxidase 4（GPX4） were detected by Western blot to clarify the regulatory effect of BXG on ferroptosis. ResultsA total of 61 chemical components in BXG intestinal absorption fluid were identified， and network pharmacology obtained 27 potential targets of BXG for the treatment of HF， as well as 139 signaling pathways. BXG may act on core targets such as STAT3， tumor protein p53（TP53）， epidermal growth factor receptor（EGFR）， JUN and prostaglandin-endoperoxide synthase 2（PTGS2） through core components such as glabrolide and limonin， which in turn intervene in lipid and atherosclerosis， phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）， endocrine resistance and other signaling pathways to exert therapeutic effects on HF. Molecular docking showed that the docking results of multiple groups of targets and compounds were good. In vitro cell experiments showed that compared with the blank group， the cell viability and survival rate of the model group were significantly decreased， the level of ROS was significantly increased（P<0.01）， the expression levels of STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 proteins were significantly decreased（P<0.05， P<0.01）. Compared with the model group， the cell viability and survival rate of the BXG group were significantly increased， the ROS level was significantly decreased（P<0.01）， the STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 protein levels were significantly increased（P<0.05， P<0.01）. ConclusionBXG may inhibit the occurrence of ferroptosis by up-regulating the expression of STAT3 and GPX4， thus exerting a therapeutic effect on HF， and flavonoids may be the key components of this role.

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）， network pharmacology， molecular docking and cell experiments， the active ingredients， possible targets and molecular mechanisms of Baoxin granules（BXG） regulating ferroptosis in the treatment of heart failure（HF） were explored. MethodsBXG intestinal absorption fluid was prepared by everted gut sac and the chemical composition contained therein were identified by UPLC-Q-TOF-MS. According to the obtained components， the potential targets of BXG were predicted， and the HF-related targets and related genes of ferroptosis were retrieved at the same time， and the intersecting targets were obtained by Venn diagram. In addition， the protein-protein interaction（PPI） network and the component-target network were constructed， and the core components and core targets were obtained by topological analysis. Then Gene Ontology（GO） function and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analysis were performed on the core targets， and molecular docking validation of the key targets and main components was carried out by AutoDockTools 1.5.7. H9c2 cells were used to establish a oxygen-glucose deprivation model， and the protective effect of BXG on cells was investigated by detecting cell viability， cell survival rate and reactive oxygen species（ROS） level. The protein expression levels of signal transducer and activator of transcription 3（STAT3）， phosphorylation（p）-STAT3 and glutathione peroxidase 4（GPX4） were detected by Western blot to clarify the regulatory effect of BXG on ferroptosis. ResultsA total of 61 chemical components in BXG intestinal absorption fluid were identified， and network pharmacology obtained 27 potential targets of BXG for the treatment of HF， as well as 139 signaling pathways. BXG may act on core targets such as STAT3， tumor protein p53（TP53）， epidermal growth factor receptor（EGFR）， JUN and prostaglandin-endoperoxide synthase 2（PTGS2） through core components such as glabrolide and limonin， which in turn intervene in lipid and atherosclerosis， phosphatidylinositol 3-kinase/protein kinase B（PI3K/Akt）， endocrine resistance and other signaling pathways to exert therapeutic effects on HF. Molecular docking showed that the docking results of multiple groups of targets and compounds were good. In vitro cell experiments showed that compared with the blank group， the cell viability and survival rate of the model group were significantly decreased， the level of ROS was significantly increased（P<0.01）， the expression levels of STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 proteins were significantly decreased（P<0.05， P<0.01）. Compared with the model group， the cell viability and survival rate of the BXG group were significantly increased， the ROS level was significantly decreased（P<0.01）， the STAT3， p-STAT3， p-STAT3/STAT3 and GPX4 protein levels were significantly increased（P<0.05， P<0.01）. ConclusionBXG may inhibit the occurrence of ferroptosis by up-regulating the expression of STAT3 and GPX4， thus exerting a therapeutic effect on HF， and flavonoids may be the key components of this role.

ObjectiveTo investigate the modifiable areal unit problem （MAUP） in the spatial pattern of Pseudostellaria heterophylla production regions and reveal the impact of statistical scales on the spatial distribution characteristics of this medicinal plant species. MethodsUsing multi-source data （literature records， field surveys， and statistical data）， we systematically analyzed the spatial patterns across three administrative levels （provincial， prefectural， and county scales）. Spatial autocorrelation （Moran's I） analysis， high-low clustering （Getis-Ord General G）， and hot/cold spot analysis （Getis-Ord Gi*） were employed. ResultsThe literature-based analysis showed that the production regions of P. heterophylla presented random distribution on the provincial scale and significant aggregation on the prefectural scale. The field survey data showed that the production regions displayed random distribution on the provincial scale but significant aggregation on both prefectural and county scales. The statistical data revealed that the production regions lacked spatial autocorrelation on the provincial scale but demonstrated significant aggregation on prefectural and county scales. ConclusionMAUP effects have substantive implications for understanding and decision-making in the arrangement of medicinal plant production regions. The county scale proves to be the most sensitive and explanatory level for analyzing the spatial pattern of P. heterophylla production regions， providing a critical foundation for habitat modeling， suitability evaluation， and ecological cultivation planning of medicinal plants.

BACKGROUND: The association of systemic inflammatory response index (SIRI) with prognosis of coronary artery disease (CAD) patients has never been investigated in a large sample with long-term follow-up. This study aimed to explore the association of SIRI with all-cause and cause-specific mortality in a nationally representative sample of CAD patients from United States. METHODS: A total of 3386 participants with CAD from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were included in this study. Cox proportional hazards model, restricted cubic spline (RCS), and receiver operating characteristic curve (ROC) were performed to investigate the association of SIRI with all-cause and cause-specific mortality. Piece-wise linear regression and sensitivity analyses were also performed. RESULTS: During a median follow-up of 7.7 years, 1454 all-cause mortality occurred. After adjusting for confounding factors, higher lnSIRI was significantly associated with higher risk of all-cause (HR = 1.16, 95% CI: 1.09-1.23) and CVD mortality (HR = 1.17, 95% CI: 1.05-1.30) but not cancer mortality (HR = 1.17, 95% CI: 0.99-1.38). The associations of SIRI with all-cause and CVD mortality were detected as J-shaped with threshold values of 1.05935 and 1.122946 for SIRI, respectively. ROC curves showed that lnSIRI had robust predictive effect both in short and long terms. CONCLUSIONS SIRI was independently associated with all-cause and CVD mortality, and the dose-response relationship was J-shaped. SIRI might serve as a valid predictor for all-cause and CVD mortality both in the short and long terms.

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.

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]

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.

BACKGROUND: Growth differentiation factor 15 (GDF-15) has been explored as a potential biomarker for various inflammatory diseases and cardiovascular events. This study aimed to assess the predictive role of GDF-15 levels in cardiovascular events and all-cause mortality, considering traditional risk factors and other biomarkers. METHODS: A prospective study was conducted and 3699 patients with stable coronary artery disease (CAD) were enrolled into the research. Baseline GDF-15 levels were measured. Median follow-up was 3.1 years during the study. We analyzed clinical variables and several biomarkers. Multivariable Cox regression analysis was performed to evaluate prognostic performance of GDF-15 levels in predicting myocardial infarction (MI), heart failure, stroke, cardiovascular death, and non-cardiovascular death. RESULTS: Baseline GDF-15 levels for 3699 patients were grouped by quartile (≤ 1153, 1153-1888, 1888-3043, > 3043 ng/L). Higher GDF-15 levels were associated with older age, male gender, history of hypertension, and elevated levels of N-terminal pro B-type natriuretic peptide (NT-pro BNP), soluble suppression of tumorigenesis-2 (sST2), and creatine (each with P < 0.001). Adjusting for established risk factors and biomarkers in Cox proportional hazards models, a 1 standard deviation (SD) increase in GDF-15 was associated with elevated risk of clinical events [hazard ratio (HR) = 2.18, 95% confidence interval (CI): (1.52-3.11)], including: MI [HR = 2.83 95% CI: (1.03-7.74)], heart failure [HR = 2.71 95% CI: (1.18-6.23)], cardiovascular and non-cardiovascular death [HR = 2.48, 95% CI (1.49-4.11)] during the median follow up of 3.1 years. CONCLUSIONS Higher levels of GDF-15 consistently provides prognostic information for cardiovascular events and all cause death, independent of clinical risk factors and other biomarkers. GDF-15 could be considered as a valuable addition to future risk prediction model in secondary prevention for predicting clinical events in patient with stable CAD.

Objective - To investigate the effect of lung flora dysbiosis on the process of pulmonary fibrosis and lung epithelial （ ） Methods - mesenchymal transition EMT in mice with silicosis. Male C57BL/6 mice of specific pathogen free grade were ， ， ， （ ） randomly divided into the blank control group silicosis model group solvent control group vancomycin VM + ampicillin （ ） ， （ ） （ ） ， AMP group metronidazole MNZ + neomycin NEO group and mixed treatment group 12 mice in each group. Except for ， ， the blank control group which was given 20.0 µL of 0.9% NaCl solution the other five groups of mice were dosed with 20.0 µL of silica dust suspension at a mass concentration of 250.0 g/L using a single tracheal drip to establish the silicosis mouse model. ： The intranasal drip method was used to treat silicosis mice in each group as following mice in the solvent control group were - ； ； given double distilled water mice in the VM+AMP group were given VM at a mass concentration of 0.5 g/L and AMP at 1.0 g/L ； mice in the MNZ+NEO group were given MNZ at a mass concentration of 1.0 g/L and NEO at 1.0 g/L mice in the mixed ， treatment group were given the same doses of the four antibiotics mentioned above all in a drip volume of 50.0 µL. Silicosis ， ， mice were treated seven days and half an hour before silica dusting and 7 14 and 21 days after silica dusting. Mouse lungtissue was collected aseptically 28 days after silica dusting. Hematoxylin eosin and Masson trichrome staining methods were - used to observe the pathological changes. Western blotting was used to detect the relative protein expression of α smooth muscle （ - ）， - （ - ） （ ） actin α SMA E cadherin E CAD and vimentin VIM . Immunohistochemistry was used to detect the relative expression of - - E CAD and VIM. Real time fluorescence quantitative polymerase chain reaction was used to detect the expression levels of （Col1a2） Results collagen type Ⅰ alpha 2 mRNA in lung tissues. The histopathological results showed that the alveoli of the ， blank control group were thin and structurally intact with few surrounding infiltrating inflammatory cells and no abnormal ， distribution of collagen fibers. The alveoli of the silicosis model group were structurally disorganized with a large number of ， ， infiltrating inflammatory cells thickened alveolar walls and cellular fibrous nodules with abundant blue collagen deposit. In the ， ， VM+AMP group MNZ+NEO group and the mixed treatment group the inflammation and fibrosis were reduced with diferent degrees in the lung tissues compared to the silicosis model group and the solvent control group. The relative expression levels of - ， Col1a2 α SMA VIM protein and mRNA in lung tissues of mice in the silicosis model group were higher than those in the blank （ P ）， -CAD control group all <0.05 and the relative expression levels of E protein were lower than those in the blank control （P ） - ， Col1a2 group <0.05 . The relative expression levels of α SMA VIM protein and mRNA in lung tissues of mice in the MNZ+ （ P ）， -CAD NEO group and the mixed treatment group were lower all <0.05 and the relative expression levels of E protein were （P ）， Conclusion higher <0.05 when compared with the silicosis model group and the solvent control group. Pulmonary fibrosis ， - was reduced in silicosis mice with interventions in lung flora where anaerobic and gram negative bacteria affected pulmonary fibrosis and dysbiosis of the lung flora affected pulmonary EMT.

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