As activated hepatic stellate cells (aHSCs) play a central role in fibrogenesis, they have become key target cells for anti-fibrotic treatment. Nevertheless, the therapeutic efficiency is constrained by the exosomes they secrete, which are linked to energy metabolism and continuously stimulate the activation of neighboring quiescent hepatic stellate cells (qHSCs). Herein, an intercellular communication interference strategy is designed utilizing paeoniflorin (PF) loaded and hyaluronic acid (HA) coated copper-doped ZIF-8 (PF@HA-Cu/ZIF-8, PF@HCZ) to reduce energy-related exosome secretion from aHSCs, thus preserving neighboring qHSCs in a quiescent state. Simultaneously, the released copper and zinc ions disrupt key enzymes involved in glycolysis to reduce bioenergy synthesis in aHSCs, thereby promoting the reversion of aHSCs to a quiescent state and further decreasing exosome secretion. Therefore, PF@HCZ can effectively sustain both aHSCs and qHSCs in a metabolically dormant state to ultimately alleviate liver fibrosis. The study provides an enlightening strategy for interrupting exosome-mediated intercellular communication and remodeling the energy metabolic status of HSCs with boosted antifibrogenic activity.

Objective　To analyze and study the status quo and deficiencies in the construction of talent teams at all levels of CDCs in Hainan Province and put forward countermeasures to provide a reference basis for the high-quality development of talent team construction in all levels of CDCs in Hainan Province. Methods Using field surveys and data retrieval, spatial analysis was employed to compare the overall differences in human resource status of the provincial-level CDC and CDCs in five regional areas (East, West, South, North, and Central Hainan). The coordination between human resource allocation and development strategies was analyzed. A descriptive analysis mainly utilized CDC survey questionnaires and other research forms to explore the health human resources of the province's CDCs. Results The professional and technical personnel in the provincial CDCs comprise 1 431 individuals, accounting for 82.3% (1 431/1 739) of the total number of actual employees, which falls short of the Central Institutional Reform Commission's (CIRC) mandate that technical professionals comprise at least 85% of the total workforce (CIRC Document [2014] No. 2). Among Hainan's CDC personnel, 115 individuals are recognized as high-level talents within the Hainan Free Trade Port framework. These include one Class C talent, 22 Class D talents, and 93 Class E talents. Class A, B, and C-level talents are deficient. The majority of staff at both the provincial and regional CDCs hold bachelor's degrees. There is a significant proportion of staff with associate degrees or lower qualifications, coupled with a severe shortage of highly educated personnel. Postgraduates with master’s degrees or above account for 27.8% (65/233) in the provincial CDC, indicating low educational credentials among personnel in Hainan's CDCs. The central region, characterized by slower economic and social development, faces greater challenges in attracting and retaining high-level talent. There is a scarcity of public health professionals with interdisciplinary expertise. Some public health staff lack clinical knowledge, experience, and skills in disease treatment. Furthermore, there is a need to strengthen on-site emergency response capabilities for public health emergencies. The structural ratio of senior, intermediate, and junior professional and technical positions in the provincial CDC is 40%∶45%∶15%. The position settings are limited to ranking levels without distinction by professional category, leading to a bottleneck-type competition like crossing the "one log bridge" for technical position promotions. Conclusion　Hainan Province faces significant challenges in developing its public health workforce, both in technical expertise and management capacity. Especially under the context of the closure operation of the Hainan Free Trade Port, it is necessary to continuously strengthen top-level talent design to cultivate a favorable policy, system, and cultural environment, thereby promoting the sustained and healthy development of the province's public health career.

OBJECTIVE: To investigate the hepatotoxicity of alkaloids from Euodiae Fructus combined with berberine (BBR) in Zuojin Pill, and to preliminarily explore the possible detoxification mechanism of the combination components. METHODS: The combination ratio of components was determined by the maximum concentration (Cmax) of the chemical components in Zuojin Pill. HepG2 cell model was used to investigate the combined toxicity of the hepatotoxic components from Euodiae Fructus, such as evodiamine (EVO) or dehydroevodiamine (DHED), with BBR for 48 h. The experimental groups were set as follows: the vehicle control group, the EVO group, the DHED group, the BBR group, and the combination group of EVO or DHED with BBR. The cell counting kit-8 (CCK-8) method was used to determine the cell viability, and the combination index (CI) was used to determine the combined toxicity of the components. The alanine transaminase (ALT), aspartate aminotransferase (AST), lactate dehydroge-nase (LDH), and alkaline phosphatase (ALP) activities as well as total bilirubin (TBIL) content in the cell culture supernatant were detected. The protein expression levels of bile acid transporters, such as bile salt export pump (BSEP) and multidrug resistance-associated protein 2 (MRP2), were detected by Western blot. The intracellular malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in HepG2 cells were detected. RESULTS: Compared with EVO or DHED group, the combination of EVO 1 μmol/L with BBR 10 μmol/L or DHED 50 μmol/L with BBR 35 μmol/L significantly increased cell viability of HepG2 cells (P < 0.01), with CI values of 77.89 or 4.49, respectively, much greater than 1. Significant decreases in the activities of ALT, AST, LDH, ALP, and TBIL content in the cell culture supernatant were found in both combination groups (P < 0.05, P < 0.01). Compared with the EVO group, the combination of EVO with BBR upregulated the protein expression levels of BSEP and MRP2. Compared with the DHED group, the combination of DHED with BBR significantly downregulated the protein expression levels of BSEP and MRP2 (P < 0.01). Compared with EVO or DHED group, the combination of EVO or DHED with BBR significantly reduced the MDA content in HepG2 cells (P < 0.05, P < 0.01). CONCLUSION A certain ratio of BBR combined with EVO or DHED had an antagonistic effect on HepG2 cytotoxicity, which might be related to regulating the expression of bile acid transpor-ters, and reducing lipid peroxidation damage.
Humans ; Hep G2 Cells ; Berberine/pharmacology* ; Drugs, Chinese Herbal/toxicity* ; Evodia/chemistry* ; Alkaloids/pharmacology* ; Cell Survival/drug effects* ; Multidrug Resistance-Associated Proteins/metabolism* ; Multidrug Resistance-Associated Protein 2 ; Quinazolines

Progressive fibrosing interstitial lung disease （PF-ILD） has a complex etiology， and is classified as lung impediment stage， impediment-atrophy combination stage， and lung atrophy stage according to the different clinical manifestations during the progression of disease. Based on the theory of opening-closing-pivoting to analyse the characteristics of yin and yang disease mechanism and the idea of prescriptions in the three stages. For lung impediment stage， main as three-Yang fail to keep inside， disharmony between Ying qi （营气） and Wei qi （卫气）， shaoyin impairment， treatment should use Mahuang （Ephedra sinica） and Guizhi （Neolitsea cassia） flexibly to form a formula， or choose pungent-dispersing formulas like Baidu Powder （败毒散） to move qi and save yang， and diffuse and disperse impediment pathogen， meanwhile combining saving-shaoyin medicinals like Fuzi （Aconitum carmichaelii） and Shudihuang （Radix Rehmanniae Praeparata） to reinforce healthy qi and dispel pathogen； for impediment-atrophy combination stage， rooted as yangming impairment and progressed by over-movement of qi， treatment should use Mahuang Shengma Decoction （麻黄升麻汤） to resolve and decrease over-activities， emphasis on both opening and closing， and improve impediment and atrophy； for lung atrophy stage with three-Yin in a bad condition simultaneously and poor prognosis， treatment should use modified Jinshui Liujun Decoction （金水六君煎） to consolidate qi and save yin， disperse phlegm and stasis， to improve the quality of life for patients with PF-ILD.

In order to understand nurses’ willingness to participate in humanistic nursing training and its influencing factors, and provide reference for managers to understand the current situation and improve nurses’ enthusiasm for humanistic nursing training. The convenience sampling method was used to investigate 23 707 nurses in 28 provinces (autonomous regions and municipalities directly under the central government) through a self-designed questionnaire distributed on the Internet. The results showed that 98.1% of nurses thought that participating in humanistic nursing related training was helpful to clinical work, but only 88.6% of the respondents were willing to participate in humanistic nursing training. Thirty factors were analyzed from four aspects of basic characteristics of individuals, cognitive relevant experience and organizational atmosphere. Fifteen factors had significant significance in binary Logistic regression analysis (P<0.05). Among them, the factors that had a positive impact on training willingness were: marriage, education, professional title, post establishment, agree with humanistic care is the basic duty of a nurse praised, experience of being praised at work, family support, rapport with patients, passion of colleagues to participate in training, sustained high-quality care demonstration activities, join the humanistic care related organization, hospital reimbursement of training expenses (OR value of 6.559~1.113, P<0.001). The OR value of humanistic nursing as a nurse’s responsibility was 6.559 and the 95%CI was 5.585~7.702. The factors that hindered nurses from participating in training were: work occupied most of time and energy, think humanistic nursing is abstract and difficult to understand, think the mastered humanistic knowledge and skills meet the needs of work (OR value of 0.657~0.722, P<0.001). Through the analysis, it is considered that nurses have a extremely consistent high recognition of the significance of humanistic nursing training, but their willingness to receive training is affected by many factors such as individual experience, cognitive attitude and organizational atmosphere. In order to realize nurses’ high recognition of humanistic nursing training to high enthusiasm of behavior, the aspects of individual cognition and organizational atmosphere must be discussed.

Objective:To analyze the medication characteristics and the rules of prescription for the treatment of acute mastitis in Puji Fang; To provide reference for the clinical treatment of acute mastitis in modern TCM. Methods:Prescriptions of the chapters of " Ruyong" and " Duru" contained in Pu Ji Fang? Fu Ren Zhu Ji Men were screened, and the prescription data were analyzed by using the ancient and modern medical record cloud platform V2.3.5 for drug frequency, properties, tastes, meridian tropism, and efficacy. Clustering analysis of high-frequency drugs and analysis of association rules were performed. Results:A total of 141 prescriptions were included, with 201 kinds of Chinese materia medica. The top ten drugs with the high frequency of use were Glycyrrhizae Radix et Rhizoma, Paeoniae Radix alba, Rhei Radix et Rhizoma, Angelicae Sinensis Radix, Astragali Radix, Olibanum, Trichosanthis Fructus, Ginseng Radix et Rhizoma, Scutellariae Radix, Gleditsiae Spina. The main property was cold, the main taste was sweet, the main meridian was spleen meridian, and the main efficacy was heat clearing and detoxification. Three types of high-frequency drugs could be obtained by clustering analysis, namely, Ginseng Radix et Rhizoma-Astragali Radix-Angelicae Sinensis Radix-Rhei Radix et Rhizoma, Scutellariae Radix-Paeoniae Radix alba-Glycyrrhizae Radix et Rhizoma, Trichosanthis Fructus-Olibanum-Gleditsiae Spina. Through correlation analysis of high-frequency drugs, it was found that there was a great correlation between Astragali Radix and Paeoniae Radix alba, Angelicae Sinensis Radix, Glycyrrhizae Radix et Rhizoma, Ginseng Radix et Rhizoma.Conclusions:The pathogenesis of acute mastitis in Pu Ji Fang is mainly damp-heat toxin and blood stasis, and deficiency of qi and blood. The treatment for strengthening healthy qi focuses on tonifying qi and blood of the liver and spleen, while the treatment for eliminating pathogenic factors focuses on removing dampness, clearing heat and toxin, resolving phlegm, dispersing stasis and removing blood stasis. In addition, according to the condition, the treatment will be increased or decreased with the disease.

Objective This study aims at establishing a teaching catalog and content for breast rare dis-eases and developing the syllabus for the breast rare disease using integrated multimodality of case-/problem-/resource-based learning(CBL+PBL+RBL).Methods By conducting bibliometrics co-occurrence analysis,we collected 6291 articles on breast rare disease published from January,1975 to June,2024.Additionally,we re-trieved the Textbook on Rare Diseases,the Catalog of Chinese Rare Disease,and Second Batch of Rare Dis-ease Catalog and then decided the teaching content.Results From 16,387 keywords,1000(6.1％)keywords were identified through co-occurrence analysis,including 50(0.3％)candidate diseases.These were classified into three categories:rare primary breast diseases,rare genetic mutation-related diseases associated with breast cancer,and rare systemic multi-system diseases involving the breast.From the candidate list,20(0.1％)rare primary breast diseases were further selected for their notable clinical teaching significance,and significant multi-systemic diseases affecting the breast,whether related to gene mutations or not.Teaching plans were draf-ted using a diversified parallel teaching approaches,taking into account the characteristics of different diseases and the focus of different teaching methods.Conclusions This study initiated the development of the teaching content for breast rare diseases and developed the teaching syllabus using the CBL+PBL+RBL integrated multi teaching model and targeting each rare breast disease for the critical point for teaching.

Objective To analyze the research hotspots and development in the field of post-stroke pneumonia over the past decade. Methods The English literature on post-stroke pneumonia in the Web of Science Core Collection database from January,2014 to June,2024 was retrieved,and analyzed using CiteSpace 6.3.R1 software. Results A total of 1 681 papers were included.The number of publications gradually increased from 2014 to 2021,and decreased from 2022 to 2024,but still more than 2014 overall.The United States and China were the countries with the highest number of publications,and most of the institutions with a high number of publications were uni-versities,while independent collaborative networks were found among the authors.Hot keywords included dys-phagia,management and venous thromboembolism,etc.;and the bursting words appeared within the last three years were scale score and mechanical thrombectomy. Conclusion The researches related to post-stroke pneumonia present an inverted U-shape in the past ten years.The rela-tionship and risk management of post-stroke pneumonia with dysphagia and venous thromboembolism are the main hotspots in the researches.The studies may tend to explore the sensitivity of the integration scale for post-stroke pneumonia and the control of risk factors during mechanical thrombectomy.

Objective To investigate the effect and mechanism of IL-17 on heart failure(HF)in hy-pertensive rats based on NF-κB/sarco-endoplasmic reticulum calcium ATPase 2(SERCA2)signa-ling pathway.Methods Thirty SPF male spontaneously hypertensive rats(SHR)aged 6-8 weeks were divided into control group,model group,phosphate buffer salt(PBS)solution injec-tion group(PBS group),IL-17 protein injection group(IL-17 group)and IL-17 and antibody injec-tion group(IL-17+IgG group),with 6 animals in each group.Hypertensive HF model was estab-lished,and corresponding agents were applied to the PBS group,IL-17 group and IL-17+IgG group intraperitoneally,respectively.The role of IL-17,NF-κB and SERCA2 in hypertensive HF was studied with HE staining,immunohistochemical assay,Western blotting,RT-qPCR and ELISA.Results Significantly higher serum levels of NT-proBNP and IL-17,enhanced myocardial expression of IL-17 mRNA and NF-κB protein,lower serum VEGF level,and down-regulated pro-tein level of SERCA2 in heart tissue were observed in the model group and the PBS group when compared with the control group(P＜0.01).The IL-17 group had obviously higher serum NT-proBNP and IL-17 levels and myocardial expression of IL-17 mRNA and NF-κB protein,and reduced serum VEGF level and SERCA2 protein level in heart tissue than the model group(P＜0.01).IL-17+IgG treatment resulted in notably lower serum IL-17 level and myocardial NF-κB protein level when compared with those of model group(8.98±1.20 vs 11.19±1.22,0.88±0.03 vs 0.93±0.03,P＜0.01),and also resulted in remarkably reduced serum levels of NT-proBNP and IL-17 and myocardial expression of IL-17 mRNA and NF-κB protein but increased serum VEGF level and SERCA2 protein level in heart tissue when compared with the IL-17 group(P＜0.01).The heart rate,SBP,IVSd,LVPWd,LVEDD and LVESD were significantly lower,while LVFS was notably higher in the IL-17+IgG group than the model group and IL-17 group(P＜0.01).The IL-17+IgG group had obviously higher LVEF than the IL-17 group[(70.81±6.50)％vs(62.77±5.43)％,P＜0.01].Conclusion IL-17/NF-κB/SERCA2 signaling pathway is involved in the regulation of inflammatory response after hypertensive HF,and inhibiting IL-17 can effective-ly improve the cardiac dysfunction caused by hypertensive HF.

OBJECTIVE To investigate the impact of mercuric sulfide nanoparticles(HgS-NP)on various neurotransmitter-type neurons in Caenorhabditis elegans(C.elegans).METHODS Wild-type N2 C.elegans,as well as the transgenic C.elegans expressing green fluorescent protein specifically in gamma-amino-butyric acid(GABA)-ergic,glutamatergic,dopaminergic,cholinergic,and serotoninergic neurons(strains EG1285,DA1240,BZ555,LX929,and GR1366),were synchronized at the L4 stage and treated with different concentrations of HgS-NP via solid exposure.① Five transgenic strains of C.elegans were exposed to HgS-NP 0(control group),250,500,and 1000 mg·L-1 for 72 h.Fluorescence microscopy was used to observe the expression of green fluorescence in different neurotransmitter-type neurons of the corresponding transgenic C.elegans.② Wild-type N2 C.elegans were exposed to HgS-NP 0(control group)and 1000 mg·L-1 for 72 h.Real-time quantitative PCR(RT-qPCR)was performed to detect the mRNA expression levels of 33 genes related to the GABAergic and glutamatergic neurotransmitter systems.RESULTS ① Compared with the control group of the same genotype,the EG1285 C.elegans exhibited soma shrinkage,dendrite fragmentation,and neuronal loss,with a significant decrease in the relative fluorescence intensity of GABAergic neurons(P<0.05)after exposure to different concentra-tions of HgS-NP.After exposure to HgS-NP 1000 mg·L-1,the DA1240 C.elegans showed a loss of glutamatergic neurons in the head region and a significant decrease in the relative fluorescence intensity(P<0.01).However,there were no significant changes in the morphology or relative fluorescence intensity of dopaminergic,cholinergic,and serotoninergic neurons in BZ555,LX929,and GR1366 C.elegans after exposure to HgS-NP,respectively.② Compared with the control group,wild-type N2 C.elegans exposed to HgS-NP 1000 mg·L-1 showed increased mRNA expression levels of glr-7 and glr-8,which encoded non-N-methyl-D-aspartate glutamate receptors(P<0.05),while the expression levels of the remaining 31 genes related to the GABAergic and glutamatergic neurotransmitter systems showed no significant changes.CONCLUSION Exposure to a high dose of HgS-NP for 72 h may potentially damage the GABAergic and glutamatergic neurons in C.elegans,but have no significant effect on dopaminergic,cholinergic or serotoninergic neurons.