In continuation of research aimed at identifying anti-inflammatory agents from natural sesquiterpenoids, an activity-guided fractionation approach utilizing lipopolysaccharide (LPS)-mediated RAW264.7 cells was employed to investigate chemical constituents from Inula Britannica (I. britannica). Seven novel sesquiterpenoid dimers inulabritanoids A-G (1-7) and two novel sesquiterpenoid monomers inulabritanoids H (8) and I (9) were isolated from I. britannica together with eighteen known compounds (10-27). The structural elucidation was accomplished through comprehensive analysis of 1D and 2D nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HR-MS), and electronic circular dichroism (ECD) spectra, complemented by quantum chemical calculations. Compounds 1, 2, 12, 16, 19, and 26 demonstrated inhibitory effects on NO production, with IC₅₀ values of 3.65, 5.48, 3.29, 6.91, 3.12, and 5.67 μmol·L^-1, respectively. Mechanistic studies revealed that compound 1 inhibited IκB kinase β (IKKβ) phosphorylation, thereby blocking nuclear factor κB (NF-κB) nuclear translocation, and activated the kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signal pathway, leading to decreased expression of NADPH oxidase 2 (NOX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), IL-1β, and IL-1α and increased expression of NAD(P)H: quinone oxidoreductase 1 (NQO-1) and heme oxygenase-1 (HO-1), thus exhibiting anti-inflammatory effects in vitro. These results indicate that dimeric sesquiterpenoids may serve as promising candidates for anti-inflammatory drug development.
Mice ; Animals ; Sesquiterpenes/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Inula/chemistry* ; RAW 264.7 Cells ; Nitric Oxide ; Molecular Structure ; NF-kappa B/immunology* ; NF-E2-Related Factor 2/immunology* ; Macrophages/immunology* ; Nitric Oxide Synthase Type II/immunology* ; Plant Extracts/pharmacology* ; Lipopolysaccharides ; Tumor Necrosis Factor-alpha/immunology* ; I-kappa B Kinase/genetics*

ObjectiveTo investigate the prevalence and associated factors of malocclusion among preschool children in Fengxian District, Shanghai, and to provide a scientific basis for local medical and public health departments to formulate targeted interventions. MethodsA cross-sectional study was conducted from September to December 2024. A total of 1 172 children aged 3‒5 years were recruited from 10 kindergartens across 5 townships in Fengxian District, using stratified cluster random sampling method. Clinical examinations were conducted to record occlusal parameters such as the relationship of the second deciduous molars, canine teeth relationship, anterior overbite and overjet, anterior and posterior crossbite, and crowded dentition. A questionnaire survey was performed to the parents to collect information on factors influencing malocclusion, including genetic predisposition, poor oral habits, dietary patterns, and sleep-related breathing conditions. Data were statistically analyzed using IBM SPSS Statistics 27 software, with chi-square test for categorical data and binary logistic regression analysis for influencing factors. ResultsThe overall prevalence of malocclusion among 3‒5-year-old children in Fengxian District of Shanghai was 70.73%, with no statistically significant differences between genders (P>0.05). Deep overbite accounted for the highest proportion (49.66%), followed by Angle Class Ⅱ malocclusion of the second deciduous molars (17.83% on the left, 19.11% on the right), midline deviation (13.23%), anterior crossbite (6.74%), and crowding of the maxillary and mandibular anterior teeth (16.38% for the maxillary dentition, 17.58% for the mandibular dentition). Multivariate analyses showed that habitual mouth breathing during the day (OR=0.509, P=0.009) and morning dry mouth upon waking (OR=1.455, P=0.023) were independent influencing factors for malocclusion. ConclusionThe prevalence of malocclusion is relatively high among preschool children in Fengxian District, Shanghai,with deep overbite being the dominant trait. Sleep-related breathing conditions (such as habitual mouth breathing during the day and morning dry mouth) is an important influencing factor for malocclusion. Public health authorities should strengthen oral health education and promote the correction of bad habits to reduce the prevalence of malocclusion and improve children’s oral health.

Objective:To study positive rates and typing of oligoclonal bands (OCB) in patients with neurological disorders, and to reveal the clinical significance and applicational value of OCB test.Methods:A retrospective analysis was performed on the detection results of 3 217 patients with neurological disorders who undertook both serum and cerebrospinal fluid OCBs in the First Hospital of Peking University from January 2012 to August 2022. According to the final diagnosis, the patients were divided into 13 groups including multiple sclerosis (479 cases), neuromyelitis optica spectrum disorders (935 cases), autoimmune encephalitis (192 cases), viral encephalitis (94 cases), nervous system complication after HSCT (232 cases), Guillain-Barré syndrome (644 cases), chronic inflammatory demyelinating polyneuropathy (157 cases), etc. Cerebrospinal fluid and serum OCBs were detected using isoelectric focusing electrophoresis combining immunofixation, then classified into Ⅰ-Ⅴ types according to the morphology. Consequently, positive rates and types were analyzed for each group. χ2 test was used for comparison between groups. Results:The positive rates of cerebrospinal fluid OCB in multiple sclerosis, nervous system complication after hematopoietic stem cell transplantation (HSCT), autoimmune encephalitis, viral encephalitis, neuromyelitis optica spectrum disorders, Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy were respectively 66.8% (320/479), 48.7% (113/232), 46.4%(89/192), 19.1% (18/94), 17.6% (165/935), 9.9% (64/644), 5.1% (8/157). For patients with multiple sclerosis, neuromyelitis optica spectrum disorders, viral encephalitis, and autoimmune encephalitis, Type Ⅱ bands took the majority of cerebrospinal fluid OCB-positive cases with the rates of 94.1% (301/320), 78.7% (70/89), 77.8% (14/18), and 77.6% (128/165) respectively, indicating intrathecal IgG synthesis; for patients with nervous system complication after HSCT, Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy, type Ⅳ bands took the majority of cerebrospinal fluid OCB-positive cases with the rates of 94.7% (107/113), 82.8% (53/64) and 100% (8/8), indicating no obvious intrathecal IgG synthesis. The positive rates of cerebrospinal fluid oligoclonal bands were significantly different among all groups (χ 2=1 268.31, P<0.001). Conclusion:The positive rates of cerebrospinal fluid oligoclonal bands are different among different neurological disorders, in which the positive rate of cerebrospinal fluid OCB is higher with type Ⅱ bands as the majority type in multiple sclerosis, which indicates that the detection and typing of cerebrospinal fluid OCB are helpful for the diagnosis of various neurological diseases, especially for multiple sclerosis.

Objective:This study aimed to investigate the correlation between the levels of serum amyloid A protein (SAA) and apolipoprotein A-Ⅰ (ApoA-Ⅰ) with the severity and prognosis of septic patients, in order to find new clinical prognostic markers for sepsis patients.Methods:This study prospectively included patients admitted to the intensive care unit of Northern Jiangsu People's Hospital from September 2021 to February 2022. Patients were diagnosed with sepsis according to the Sepsis-3 criteria and aged between 18 and 80 years old. Peripheral venous blood samples were collected at 0 h, 24 h, and 72 h after inclusion in the study, measured the levels of ApoA-Ⅰ and SAA, and the 72 h ΔSAA and 72 h ΔApoA-Ⅰwere calculated.. Patient demographics, laboratory parameters, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) scores, sequential organ failure assessment scores, etc., were recorded. Patients were divided into survival and death groups based on outcomes, and were divided into shock and non-shock groups based on the presence of shock. Logistic regression was used to combine ApoA-I and SAA to establish a new combined index. Receiver Operating Characteristic curve analysis was performed to evaluate the predictive value of SAA, ApoA-Ⅰ, 72 h ΔApoA-Ⅰ, 72 h ΔSAA and the combined SAA and ApoA-Ⅰ for the prognosis of sepsis patients.Results:A total of 108 patients were included in the analysis, with 48 cases in the non-septic shock group and 60 cases in the septic shock group; 77 cases in the survival group and 31 cases in the death group. There were statistically significant differences in SAA and ApoA-Ⅰ levels at each time point between the shock and non-shock groups (all P<0.05), as well as between the death and survival groups (all P<0.05). SAA levels at each time point were positively correlated with APACHEⅡ scores (all P<0.001), while ApoA-Ⅰ levels at each time point were negatively correlated with APACHEⅡ scores (all P<0.01). SAA levels could predict the risk of death in sepsis patients, with the highest area under curve (AUC) value at 24 h SAA (AUC=0.713, P=0.001), sensitivity was 65.3%, and specificity was 72.7% for predicting 28-day mortality in sepsis. ApoA-Ⅰ levels at each time point could also predict the risk of death in sepsis patients, with the highest AUC value at 72 h ApoA-Ⅰ (AUC=0.743, P<0.001), sensitivity was 69.4%, and specificity was 77.1% for predicting 28-day survival in sepsis. The combined detection of 24 h SAA and 72 h ApoA-Ⅰ increased the AUC value (AUC=0.758, P<0.05), but the Z test showed that the prediction of death risk in patients with sepsis was not significantly higher than that of a single index ( P>0.05). Conclusions:Serum levels of SAA and ApoA-Ⅰ could reflect the severity of sepsis in patients and serve as independent indicators for predicting the prognosis of sepsis patients. The overall diagnostic efficacy of the combined SAA and ApoA-Ⅰ was not significantly different from that of a single index.

Objective:To analyze the distribution and drug resistance of the pathogen of bloodstream infections in patients with malignancies in Shanxi Province Cancer Hospital.Methods:A retrospective case series study was conducted. A total of 8 654 patients with malignancies whose blood culture was detected in Shanxi Province Cancer Hospital between January 2019 and December 2021 were collected, and venous blood was drawn for blood culture. WHONET 5.6 software and SPSS 23.0 software were used to analyze the distribution and drug resistance of the pathogen of bloodstream infections.Results:A total of 600 (6.9%) pathogens were isolated, including 413 (68.8%) strains of Gram-negative bacteria, 168 (28.0%) strains of Gram-positive bacteria, 19 (3.2%) strains of fungi. The top 5 gram-negative bacteria were Escherichia coli (37.7%), Klebsiella pneumoniae (14.2%), Enterobacter cloacae (4.5%), Pseudomonas aeruginosa (3.0%), and Acinetobacter baumannii (2.5%). The top 5 gram-positive bacteria were Staphylococcus aureus (4.2%), Enterococcus faecium (4.0%), Staphylococcus hominis (3.8%), Staphylococcus epidermidis (3.5%) and Streptococcus (3.0%); except Klebsiella pneumoniae, there were no statistically significant differences in the composition ratio of other major pathogens from 2019 to 2021 (all P > 0.05). The resistance rates of Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae to ampicillin were 94.7% (214/226), 100.0% (85/85) and 96.3% (26/27); the resistance rates of those to ciprofloxacin were 61.9% (140/226), 17.6% (15/85) and 7.4% (2/27); and the resistance rates of those to cefoperazone were 62.4% (141/226), 30.6% (26/85) and 25.9% (7/27), respectively. The resistance rates of P. aeruginosa and Acinetobacter baumannii to carbapenems were 5.5% (1/18) and 93.3% (14/15). Staphylococcus aureus, Staphylococcus hominis, Staphylococcus epidermidis were predominantly Staphylococcus. Enterococcus faecium and Enterococcus faecalis were the main types of enterococcus. Positive blood culture samples were mainly distributed in hematology department and intensive care unit. Non-Hodgkin lymphoma (39 strains) and acute myeloid leukemia (12 strains) were the main diseases. Conclusions:The main pathogen of bloodstream infection in patients with malignancies in this area is Gram-negative bacteria, and drug resistance is common. Hospitals should rationally use antibiotics by combining with drug sensitivity test.

Existing traditional Chinese medicine (TCM)-related databases are still insufficient in data standardization, integrity and precision, and need to be updated urgently. Herein, an Encyclopedia of Traditional Chinese Medicine version 2.0 (ETCM v2.0, http://www.tcmip.cn/ETCM2/front/#/) was constructed as the latest curated database hosting 48,442 TCM formulas recorded by ancient Chinese medical books, 9872 Chinese patent drugs, 2079 Chinese medicinal materials and 38,298 ingredients. To facilitate the mechanistic research and new drug discovery, we improved the target identification method based on a two-dimensional ligand similarity search module, which provides the confirmed and/or potential targets of each ingredient, as well as their binding activities. Importantly, five TCM formulas/Chinese patent drugs/herbs/ingredients with the highest Jaccard similarity scores to the submitted drugs are offered in ETCM v2.0, which may be of significance to identify prescriptions/herbs/ingredients with similar clinical efficacy, to summarize the rules of prescription use, and to find alternative drugs for endangered Chinese medicinal materials. Moreover, ETCM v2.0 provides an enhanced JavaScript-based network visualization tool for creating, modifying and exploring multi-scale biological networks. ETCM v2.0 may be a major data warehouse for the quality marker identification of TCMs, the TCM-derived drug discovery and repurposing, and the pharmacological mechanism investigation of TCMs against various human diseases.

BACKGROUND: Changes in white matter (WM) underlie the neurocognitive damages induced by a human immunodeficiency virus (HIV) infection. This study aimed to examine using a bundle-associated fixel-based analysis (FBA) pipeline for investigating the microstructural and macrostructural alterations in the WM of the brain of HIV patients. METHODS: This study collected 93 HIV infected patients and 45 age/education/handedness matched healthy controls (HCs) at the Beijing Youan Hospital between January 1, 2016 and December 30, 2016.All HIV patients underwent neurocognitive evaluation and laboratory testing followed by magnetic resonance imaging (MRI) scanning. In order to detect the bundle-wise WM abnormalities accurately, a specific WM bundle template with 56 tracts of interest was firstly generated by an automated fiber clustering method using a subset of subjects. Fixel-based analysis was used to investigate bundle-wise differences between HIV patients and HCs in three perspectives: fiber density (FD), fiber cross-section (FC), and fiber density and cross-section (FDC). The between-group differences were detected by a two-sample t -test with the false discovery rate (FDR) correction ( P <0.05). Furthermore, the covarying relationship in FD, FC and FDC between any pair of bundles was also accessed by the constructed covariance networks, which was subsequently compared between HIV and HCs via permutation t -tests. The correlations between abnormal WM metrics and the cognitive functions of HIV patients were explored via partial correlation analysis after controlling age and gender. RESULTS: Among FD, FC and FDC, FD was the only metric that showed significant bundle-wise alterations in HIV patients compared to HCs. Increased FD values were observed in the bilateral fronto pontine tract, corona radiata frontal, left arcuate fasciculus, left corona radiata parietal, left superior longitudinal fasciculus III, and right superficial frontal parietal (SFP) (all FDR P <0.05). In bundle-wise covariance network, HIV patients displayed decreased FD and increased FC covarying patterns in comparison to HC ( P <0.05) , especially between associated pathways. Finally, the FCs of several tracts exhibited a significant correlation with language and attention-related functions. CONCLUSIONS Our study demonstrated the utility of FBA on detecting the WM alterations related to HIV infection. The bundle-wise FBA method provides a new perspective for investigating HIV-induced microstructural and macrostructural WM-related changes, which may help to understand cognitive dysfunction in HIV patients thoroughly.
Humans ; HIV ; HIV Infections ; Cognition ; Brain ; White Matter

Objective:To evaluate the competence of head nurses by using the in-basket test for establishing a hierarchical training system for these nurses.Methods:A set of in-basket test was independently designed to evaluate the head nurses of a tertiary hospital in September 2021.Fourteen competency indicators, including positive initiative, coordination and communication ability, and leadership, problem solving ability, motivation, empowerment, attention to quality and order, etc, were selected to analyze the answers of the in-basket test and score their competency level. The measures were described by Mean±SD and M(IQR), and the counts were described by rates and percentages. The rank sum test and multiple linear regression were used to analyze the influencing factors of competency scoring of head nurses. Results:A total of 133 head nurses were tested, with a total competency scoring of 30.0(5.5). The highest indicators were talent cultivation 3.0(2.0), positive initiative 3.0(1.0), coordination and communication ability 3.0(1.0), while those with lower scores were empowerment 1.0(1.0) and motivation 1.5(1.5). The rank sum test analysis showed that age, position, job position character and working seniority were the influencing factors of competency score( P<0.05). The multiple linear regression analysis showed that, working seniorities of 16-20 years( β=0.583, P=0.013), 21-25 years( β=0.732, P=0.008), 26-30 years( β=0.632, P=0.026) were the influencing factors of competency score of head nurses. Conclusions:The in-basket test is practical to evaluate the competence of head nurses as a basis for their targeted training in the future.

The clinical data of a case of paroxysmal extreme pain disorder(PEPD) in Guangdong 999 Brain Hospital were retrospectively analyzed.The male patient, age of first examination was 7 months, began to have recurrent tonic accompanied by facial redness or cyanosis at 5 months after birth.The patient was diagnosed with epilepsy.The oral solution of sodium valproate and Levetiracetam were not effective.The video electroencephalogram examination displayed that, when the patient had tonic and bradycardia, the synchro electroencephalogram did not show epileptic discharge, so the patient was considered to have non-epileptic tonic.Genetic examination suggested that SCN9A gene mutation of c. 5240T >C resulted in amino acid changes: Val1747Ala.Combined with the skin changes, the patient was diagnosed as PEPD caused by SCN9A gene mutation.After the treatment with Carbamazepine, the patient′s abnormal skin changed and his-epileptic tonic disappeared, and his condition improved significantly.The early stage of PEPD can be mainly manifested as non-epileptic tonic.It is easy to be misdiagnosed as epilepsy, so the patient′s characteristic skin changes should be noticed, and genetic examination is also helpful in the diagnosis of the disease.