OBJECTIVE To investigate the immunotoxicity and potential mechanism of Carthamus tinctorius extract on RBL-2H3 cells via direct induction and induction by sensitized serum prepared with an overdose of the extract. METHODS For direct induction by C. tinctorius extract， RBL-2H3 cells were divided into normal control group （no treatment） and C. tinctorius extract group （10 mg/mL）. For induction by sensitized serum prepared with an overdose of C. tinctorius extract， rats were divided into normal control group （no treatment）， adjuvant-treated group （1 mL adjuvant）， C. tinctorius extract-induced sensitization group （2.04 g/mL）， and ovalbumin （OVA）-induced sensitization group （50 mg/mL）. Sensitization was performed once every other day for a total of 3 times. Morphological changes of RBL-2H3 cells were observed， the degranulated rate of cells was counted， and histamine content was determined； the release rate of β -hexosaminidase （ β -Hex） was calculated， the levels of interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） and intracellular Ca²⁺ concentration were detected. RESULTS Under direct induction by C. tinctorius extract， compared with the normal control group， the volume of cells in the C. tinctorius extract group was significantly reduced and cell density decreased； the degranulation rate of cells， histamine content， β -Hex release rate， IL-6 and TNF-α levels， as well as intracellular Ca²⁺ concentration were all significantly increased （ P ＜0.01）. Under i nduction by sensitized serum prepared with an overdose of C. tinctorius extract， compared with the adjuvant-treated group， the above indicators in the C. tinctorius extract-induced sensitization group and the OVA-induced sensitization group showed consistent changes with those in the C. tinctorius extract group under direct induction， all being significantly elevated （ P ＜0.01）. CONCLUSIONS C. tinctorius extract may affect degranulation of RBL-2H3 cells and promote Ca²⁺ influx accompanied by the release of pro-inflammatory cytokines through two approaches： direct induction and induction by sensitized serum prepared under overdose administration. Its mechanism may be related to the activation of the calcium signaling pathway and the regulation of inflammatory pathways under the synergistic effect of multiple components.

OBJECTIVE To formulate Guidelines for the standardized implementation of pharmacist-managed clinics （ 2026 edition ） in response to the challenges faced by such clinics in China， including uneven development， large discrepancies in service specifications， insufficient patient awareness， and limited medical insurance coverage. METHODS Led by the Pharmaceutical Affairs Professional Committee of the Chinese Hospital Association， the Evidence-based Pharmacy Professional Committee of the Chinese Pharmaceutical Association， and the Hospital Pharmacy Professional Committee of the Cross-strait Medical and Health Exchange Association， a total of 19 domestic hospital pharmacy experts were organized. Through a systematic review of national policies and literature research， current practical experience was summarized. Consensus on the contents of the guidelines was reached after in-depth discussions. RESULTS &CONCLUSIONS The guidelines covered five sections： definition and connotation of pharmacist-managed clinics， establishment requirements， implementation and management， post competency， and practical research. Firstly， the definition and connotation included three operational forms of pharmacist-managed clinics （independent mode， physician-pharmacist joint mode， and online pharmacist-managed clinic mode） and classified service modes （specialty-specific， drug-specific， and disease-specific pharmacist-managed clinics）. The establishment requirements were further refined， covering system construction （pharmaceutical service management system， quality control and assessment mechanism）， personnel qualifications （professional credentials， continuing education and professional training， etc）， service recipients， as well as service venues and facilities. Subsequently， the implementation and management of pharmacist-managed clinics were proposed， involving service procedures， intervention measures， documentation and records， patient education and follow-up， humanistic care， as well as risk management and quality control. Finally， post competency encompassed the competency requirements for pharmacists providing services in pharmacist-managed clinics， as well as the suggestions on teaching methods； practical research encouraged the conduct of high-quality pharmaceutical practice in the setting of pharmacist-managed clinics. The guidelines provide valuable guidance for the standardized implementation of pharmacist-managed clinics in China in terms of establishment， management， teaching， and research， fill the guideline gap in this field， and can promote the high-quality development of pharmacist-managed clinics.

Objective To investigate the relationship between the comorbidity of dyslipidemia, hypertension and diabetes and lifestyle of adult residents in Hebei Province in 2018, and to provide reference for the development of chronic diseases prevention measures. Methods Using data from the surveillance of chronic diseases and their risk factors among adults in Hebei in 2018, 7 711 permanent residents aged ≥18 years were selected as the research subjects. Multivariate logistic regression analysis was used to analyze the relationship between the comorbidity of dyslipidemia, hypertension, and diabetes and lifestyle in adult residents. Results A total of 7 711 subjects aged ≥18 years were included in 2018. The comorbidity rates of hypertension and dyslipidemia, diabetes and dyslipidemia, and hypertension and diabetes were 16.88%, 7.91%, and 8.13%, respectively. The comorbidity rate of hypertension, diabetes, and dyslipidemia was 22.65%. These comorbidity rates increased with age and BMI. Multivariate logistic regression results showed that male, age, overweight/obesity, physical inactivity, daily sedentary behavior time ≥5 hours, and sleep problems were risk factors for the comorbidity of the "three highs". Conclusion The prevalence of the "three highs" comorbidities is relatively high in Hebei Province, and there are multiple common risk factors. Maintaining a healthy lifestyle and implementing comprehensive prevention and control measures are the key to improving the health level of residents.

Objective To investigate the influencing factors of stroke patients with hypertension and their compliance with antihypertensive drugs, and to provide targeted intervention measures for stroke prevention in hypertensive patients.  Methods Using the method of multi-stage cluster sampling, a total of 59,434 permanent residents aged 40 and above were selected from 48 monitoring sites in 9 cities of Hebei Province from December 2019 to December 2020. Unconditional logistic regression analysis was used to explore the influencing factors of stroke complicated with hypertension and the compliance of patients with antihypertensive drugs.  Results Among the 59 434 subjects, the prevalence rate of stroke was 4.33% and the prevalence rate of stroke complicated with hypertension was 82.47%. The results of univariate analysis showed that the proportion of women, rural areas, dyslipidemia, diabetes, obesity, and people with family history of stroke was higher in stroke patients with hypertension, and the difference was statistically significant (P<0.05). Multivariate logistic regression analysis showed that rural areas, dyslipidemia, diabetes, obesity, and family history of stroke significantly increased the risk of stroke, and the OR (95%CI) values were 1.29 (1.03-1.62), 1.39 (1.12-1.72), 1.58 (1.25-1.99), 1.61 (1.22-2.12) and 1.60 (1.26-2.04), respectively. Among stroke patients with hypertension, 92.71% of patients took antihypertensive drugs. It was found that women's compliance with antihypertensive drugs was good, with an OR (95%CI) value of 1.46 (1.01-2.09).  Conclusion The prevalence rate of stroke complicated with hypertension is high in people aged 40 and above in Hebei Province. Hypertensive people should lower blood lipids, control blood glucose, and lose weight as soon as possible to prevent the occurrence of stroke.

Objective To summarize the clinical features and prognosis of children suffered from malignant solid tumors of head and neck.Methods The clinical data of children with primary malignant solid tumors located in the head and neck was retrospectively analyzed from January 2007 to December 2021 in the Department of Oncology,Beijing Children's Hospital,Capital Medical University,and the clinical features,prognostic factors were summarized.Results A total of 234 children with malignant solid tumors of head and neck were included,with a male to female ratio of 1∶0.7,aged from 3 months to 17 years and 6 months(median age 51 months).173 cases(73.9％)were treated with local painless masses.Other symptoms included snoring and facial paralysis.The proportion of rhabdomyosarcoma(RMS)was the highest(145 cases,62.0％),followed by neuroblastoma(NB)(25 cases,10.7％),Ewing sarcoma(19 cases,8.1％),etc.A total of 47 cases(20.1％)had distant metastasis.The patients received surgery,chemotherapy and radiotherapy under the mode of multidisciplinary treatment(MDT).The 3-year and 5-year overall survival(OS)were 80.8％and 75.8％,respectively,and the 3-year and 5-year progression free survival(PFS)were 64.0％and 58.9％,respectively.Tumor survivors had abnormal appearance or facial motor function(49 cases,41.2％),developmental problems or abnormal tooth loss(18 cases,15.1％),and other long-term complications that may be related to the tumor or treatment.Conclusion There are various pathologic types of pediatric head and neck malignant solid tumors,RMS and NB are the most common.Local painless mass was the most common complaint.Distant metastasis is an independent risk factor for the prognosis of head and neck malignant solid tumors.Under the MDT model,the prognosis of malignant solid tumors of the head and neck in our center was generally good.In the treatment of the tumors,the side effects and sequelae should be controlled as small as possible under the premise of long-term survival.

Objective:To analyze the prevalence of chronic kidney disease (CKD) and influencing factors of adults in Hebei Province, and provide scientific evidence for the development of comprehensive CKD prevention and control strategies.Methods:In China Adult Chronic Disease and Nutrition Surveillance in Hebei in 2018, a total of 7 562 permanent residents aged ≥18 years were selected by multi-stage stratified cluster random sampling from 13 surveillance points in Hebei for questionnaire survey, medical examination and laboratory test.Results:A total of 1 067 CKD patients were detected in the adults aged ≥18 years in this survey, with a weighted prevalence rate of 12.10%. The results of multivariate analysis showed that the daily total static behavior time ( OR=1.07, 95% CI: 1.04-1.09), living in rural area ( OR=1.50, 95% CI: 1.14-1.97), coal use ( OR=1.37, 95% CI: 1.16-1.61), coal gas/liquefied gas/natural gas/biogas use ( OR=2.92, 95% CI: 2.40-3.54) and solar energy/electricity use ( OR=1.75, 95% CI: 1.36-2.25), insufficient fruit intake ( OR=1.39, 95% CI: 1.06-1.83), insufficient physical activity ( OR=1.35, 95% CI: 1.11-1.64), suffering from hypertension ( OR=1.80, 95% CI: 1.44-2.24) and suffering from diabetes ( OR=1.77, 95% CI: 1.27-2.45) were risk factors for CKD in adults in Hebei. High education level ( OR=0.41, 95% CI: 0.19-0.91), excessive drinking ( OR=0.53, 95% CI: 0.28-0.99), central obesity ( OR=0.75, 95% CI: 0.58-0.97), history of allergic diseases ( OR=0.44, 95% CI: 0.27-0.72) were protective factors for CKD. Conclusions:The prevalence of CKD in adults in Hebei was relatively high, especially in those who had too long average daily static behavior, lived in rural area, used coal, gas/liquefied gas/natural gas/biogas, solar energy/electricity, had inadequate intake of fruits, lacked physical activity and suffered from hypertension and diabetes. It is necessary to pay attention to the early prevention and treatment of CKD, strengthen the health education about healthy lifestyle and improve the management of patients with chronic disease, such as hypertension and diabetes, to further reduce the risk for CKD.

Nipah virus (NiV) and related viruses form a distinct henipavirus genus within the Paramyxoviridae family. NiV continues to spillover into the humans causing deadly outbreaks with increasing human-bat interaction. NiV encodes the large protein (L) and phosphoprotein (P) to form the viral RNA polymerase machinery. Their sequences show limited homologies to those of non-henipavirus paramyxoviruses. We report two cryo-electron microscopy (cryo-EM) structures of the Nipah virus (NiV) polymerase L-P complex, expressed and purified in either its full-length or truncated form. The structures resolve the RNA-dependent RNA polymerase (RdRp) and polyribonucleotidyl transferase (PRNTase) domains of the L protein, as well as a tetrameric P protein bundle bound to the L-RdRp domain. L-protein C-terminal regions are unresolved, indicating flexibility. Two PRNTase domain zinc-binding sites, conserved in most Mononegavirales, are confirmed essential for NiV polymerase activity. The structures further reveal anchoring of the P protein bundle and P protein X domain (XD) linkers on L, via an interaction pattern distinct among Paramyxoviridae. These interactions facilitate binding of a P protein XD linker in the nucleotide entry channel and distinct positioning of other XD linkers. We show that the disruption of the L-P interactions reduces NiV polymerase activity. The reported structures should facilitate rational antiviral-drug discovery and provide a guide for the functional study of NiV polymerase.
Nipah Virus/chemistry* ; Cryoelectron Microscopy ; Viral Proteins/genetics* ; RNA-Dependent RNA Polymerase/genetics* ; Phosphoproteins/genetics* ; Humans ; Models, Molecular ; Protein Binding

Objective To investigate the effects of hyaluronic acid and proteoglycan-linked protein 1 (HAPLN1) secreted by synovial fibroblasts (FLS) on the polarization of macrophages (Mϕ) in rheumatoid arthritis (RA). Methods Human monocytic leukemia cells (THP-1) were differentiated into Mϕ, which were subsequently exposed to recombinant HAPLN1 (rHAPLN1). RA-FLS were transfected separately with HAPLN1 overexpression plasmid (HAPLN1^OE) or small interfering RNA targeting HAPLN1 (si-HAPLN1), and then co-cultured with Mϕ to establish a co-culture model. The viability of Mϕ was assessed using the CCK-8 assay, and the proportions of pro-inflammatory M1-type and anti-inflammatory M2-type Mϕ were analyzed by flow cytometry. Additionally, the expression levels of inflammatory markers, including interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), and inducible nitric oxide synthase (iNOS), were quantified using quantitative real-time PCR and Western blot analysis. Results The viability of Mϕ was increased in the rHAPLN1 group compared to the control group. Furthermore, both the M1/Mϕ ratio and inflammatory factor levels were elevated in the rHAPLN1 and HAPLN1^OE groups. In contrast, the si-HAPLN1 group exhibited a decrease in the M1/Mϕ ratio and inflammatory factor expression. Notably, the introduction of rHAPLN1 in rescue experiments further promoted Mϕ polarization towards the M1 phenotype. Conclusion HAPLN1, secreted by RA fibroblast-like synoviocytes (RA-FLS), enhances Mϕ polarization towards the M1 phenotype.
Humans ; Arthritis, Rheumatoid/genetics* ; Macrophages/immunology* ; Fibroblasts/metabolism* ; Phenotype ; Extracellular Matrix Proteins/genetics* ; Proteoglycans/genetics* ; Synovial Membrane/cytology* ; Tumor Necrosis Factor-alpha/genetics* ; Interleukin-1beta/genetics* ; Nitric Oxide Synthase Type II/genetics* ; Cell Differentiation ; Coculture Techniques ; THP-1 Cells

Objective:To analyze the prevalence of chronic kidney disease (CKD) and influencing factors of adults in Hebei Province, and provide scientific evidence for the development of comprehensive CKD prevention and control strategies.Methods:In China Adult Chronic Disease and Nutrition Surveillance in Hebei in 2018, a total of 7 562 permanent residents aged ≥18 years were selected by multi-stage stratified cluster random sampling from 13 surveillance points in Hebei for questionnaire survey, medical examination and laboratory test.Results:A total of 1 067 CKD patients were detected in the adults aged ≥18 years in this survey, with a weighted prevalence rate of 12.10%. The results of multivariate analysis showed that the daily total static behavior time ( OR=1.07, 95% CI: 1.04-1.09), living in rural area ( OR=1.50, 95% CI: 1.14-1.97), coal use ( OR=1.37, 95% CI: 1.16-1.61), coal gas/liquefied gas/natural gas/biogas use ( OR=2.92, 95% CI: 2.40-3.54) and solar energy/electricity use ( OR=1.75, 95% CI: 1.36-2.25), insufficient fruit intake ( OR=1.39, 95% CI: 1.06-1.83), insufficient physical activity ( OR=1.35, 95% CI: 1.11-1.64), suffering from hypertension ( OR=1.80, 95% CI: 1.44-2.24) and suffering from diabetes ( OR=1.77, 95% CI: 1.27-2.45) were risk factors for CKD in adults in Hebei. High education level ( OR=0.41, 95% CI: 0.19-0.91), excessive drinking ( OR=0.53, 95% CI: 0.28-0.99), central obesity ( OR=0.75, 95% CI: 0.58-0.97), history of allergic diseases ( OR=0.44, 95% CI: 0.27-0.72) were protective factors for CKD. Conclusions:The prevalence of CKD in adults in Hebei was relatively high, especially in those who had too long average daily static behavior, lived in rural area, used coal, gas/liquefied gas/natural gas/biogas, solar energy/electricity, had inadequate intake of fruits, lacked physical activity and suffered from hypertension and diabetes. It is necessary to pay attention to the early prevention and treatment of CKD, strengthen the health education about healthy lifestyle and improve the management of patients with chronic disease, such as hypertension and diabetes, to further reduce the risk for CKD.

Objective To analyze the interspecies differences in virulence of different carbapenem-resistant Enterobacterales(CREb)strains and provide a theoretical basis for understanding the pathogenic mechanisms of CREb and for guiding individualized treatment strategies.Methods A total of nine CREb clinical isolates collected between 2013 and 2022 were included,representing five species:Enterobacter cloacae(E.cloacae),Enterobacter hormaechei(E.hormaechei),Enterobacter kobei(E.kobei),Enterobacter asburiae(E.asburiae),and Enterobacter chuandaensis(E.chuandaensis).Whole-genome sequencing was performed to characterize virulence gene profiles.Phenotypic assays included growth curve analysis,biofilm formation assessment,serum bactericidal assays,and Galleria mellonella infection models to evaluate virulence-related traits.Results Virulence gene analysis revealed that motility-related factors were the most abundant(16 to 20 per strain),followed by nutrition/metabolism-related factors(10 to 12 per strain),while invasion-related genes were rare,with the ibeB gene detected in only two E.asburiae strains.The strains of the same species shared similar viru-lence gene profiles,and E.chuandaensis harbored the fewest virulence genes.In vitro growth assays showed that E.hormaechei and E.cloacae had the fastest growth rates,while E.chuandaensis and E.kobei exhibited slower growth,and E.asburiae displayed the slo-west growth.Biofilm assays indicated that E.hormaechei and E.cloacae had the strongest biofilm-forming capacity,while E.kobei had the weakest.In serum bactericidal assays,E.hormaechei and E.cloacae showed high survival rates(＞70%),whereas the survival rate of E.chuandaensis was less than 1%.In the Galleria mellonella model,E.asburiae and E.cloacae exhibited marked dose-dependent virulence,whereas the remaining strains showed reduced virulence.Conclusion Different CREb species exhibit significant variation in virulence gene content and phenotypic traits.The pathogenic potential of CREb may provide fundamental data to inform strategies for prevention and treatment of CREb infection.