Background: Medicinal plants rich in endophytic fungi are a significant source of natural lead compounds. Meroterpenoids, which are hybrid natural products originating from partially terpenoid pathways, exhibit impressive structural complexity and substantial potential as drug candidates. The structural diversity of meroterpenoids is largely attributed to the functional diversity of terpenoid cyclases, which generate a variety of terpenoid compounds with different ring systems. This enzymatic versatility underscores the biochemical potential of endophytic fungi and their invaluable role in drug discovery. Objective: The aim of the study was to investigate the role of endophytic fungi from Paris polyphylla var. yunnanensis in facilitating diverse cyclization modifications of meroditerpenoids through four terpene cyclases (TCs) from the Pyr4 family. Methods: This study utilized a recombinant strategy to successfully reconstruct four distinct TCs from endophytic fungi in the heterologous host, Aspergillus oryzae NSAR1. The structural characterization of the resulting secondary metabolites was performed using mass spectrometry and NMR techniques. Results: The substitution of TCs from the endophytes Aspergillus felis 0260 and Fusarium graminearum 1962 in Aspergillus oryzae through hydrophobic intermediates 1 and 2, led to the production of meroditerpenoids sartorypyrone C (3) and a new compound, 4′-methylchevalone E (4), respectively. This study demonstrates the critical role of endophytic fungi in enhancing structural diversity. Conclusions: These findings provide valuable insights into the compatibility of pathway combinations and the interchangeability of terpene cyclases derived from endophytic fungi in medicinal plants, which advanced the understanding of meroditerpenoid biosynthesis and highlighted the importance of endophytic fungi in drug discovery.

Background: Medicinal plants rich in endophytic fungi are a significant source of natural lead compounds. Meroterpenoids, which are hybrid natural products originating from partially terpenoid pathways, exhibit impressive structural complexity and substantial potential as drug candidates. The structural diversity of meroterpenoids is largely attributed to the functional diversity of terpenoid cyclases, which generate a variety of terpenoid compounds with different ring systems. This enzymatic versatility underscores the biochemical potential of endophytic fungi and their invaluable role in drug discovery. Objective: The aim of the study was to investigate the role of endophytic fungi from Paris polyphylla var. yunnanensis in facilitating diverse cyclization modifications of meroditerpenoids through four terpene cyclases (TCs) from the Pyr4 family. Methods: This study utilized a recombinant strategy to successfully reconstruct four distinct TCs from endophytic fungi in the heterologous host, Aspergillus oryzae NSAR1. The structural characterization of the resulting secondary metabolites was performed using mass spectrometry and NMR techniques. Results: The substitution of TCs from the endophytes Aspergillus felis 0260 and Fusarium graminearum 1962 in Aspergillus oryzae through hydrophobic intermediates 1 and 2, led to the production of meroditerpenoids sartorypyrone C (3) and a new compound, 4′-methylchevalone E (4), respectively. This study demonstrates the critical role of endophytic fungi in enhancing structural diversity. Conclusions: These findings provide valuable insights into the compatibility of pathway combinations and the interchangeability of terpene cyclases derived from endophytic fungi in medicinal plants, which advanced the understanding of meroditerpenoid biosynthesis and highlighted the importance of endophytic fungi in drug discovery.

Background: Medicinal plants rich in endophytic fungi are a significant source of natural lead compounds. Meroterpenoids, which are hybrid natural products originating from partially terpenoid pathways, exhibit impressive structural complexity and substantial potential as drug candidates. The structural diversity of meroterpenoids is largely attributed to the functional diversity of terpenoid cyclases, which generate a variety of terpenoid compounds with different ring systems. This enzymatic versatility underscores the biochemical potential of endophytic fungi and their invaluable role in drug discovery. Objective: The aim of the study was to investigate the role of endophytic fungi from Paris polyphylla var. yunnanensis in facilitating diverse cyclization modifications of meroditerpenoids through four terpene cyclases (TCs) from the Pyr4 family. Methods: This study utilized a recombinant strategy to successfully reconstruct four distinct TCs from endophytic fungi in the heterologous host, Aspergillus oryzae NSAR1. The structural characterization of the resulting secondary metabolites was performed using mass spectrometry and NMR techniques. Results: The substitution of TCs from the endophytes Aspergillus felis 0260 and Fusarium graminearum 1962 in Aspergillus oryzae through hydrophobic intermediates 1 and 2, led to the production of meroditerpenoids sartorypyrone C (3) and a new compound, 4′-methylchevalone E (4), respectively. This study demonstrates the critical role of endophytic fungi in enhancing structural diversity. Conclusions: These findings provide valuable insights into the compatibility of pathway combinations and the interchangeability of terpene cyclases derived from endophytic fungi in medicinal plants, which advanced the understanding of meroditerpenoid biosynthesis and highlighted the importance of endophytic fungi in drug discovery.

Immune checkpoints include a series of receptor-ligand pairs that play a key role in the proliferation, activation, and immune regulatory responses of immune cells. Although immune checkpoint inhibitors (ICIs), such as programmed death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) have achieved good therapeutic effects in clinical practice, some patients still experience ineffective treatment and immune resistance. A large amount of evidence has shown that immune checkpoint proteins are related to cell metabolism during immune regulation. On the one hand, immune checkpoints connect to alter the metabolic reprogramming of tumor cells to compete for nutrients required by immune cells. On the other hand, immune checkpoints regulate the metabolic pathways of immune cells, such as phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) to affect the activation of immune cells. Based on a review of the literature, this article reviews the mechanisms by which PD-1, CTLA-4, T cell immunoreceptor with Ig and ITIM domains (TIGIT), T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), cluster of differentiation 47 (CD47), and indoleamine 2,3-dioxygenase 1 (IDO1) regulate cell metabolic reprogramming, and looks forward to whether targeting the ligand-receptor pairs of immune checkpoints in a "dual regulation" manner and inhibiting metabolic pathways can effectively solve the problem of tumor immune resistance.
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Humans ; Neoplasms/genetics* ; Metabolic Networks and Pathways/immunology* ; Animals ; Immune Checkpoint Inhibitors/pharmacology*

Objective To understand the current situation of healthcare-associated infection(HAI)in China,pro-vide data support and decision-making basis for formulating scientific and effective strategies for HAI prevention and control.Methods A nationwide cross-sectional survey on HAI was conducted among various types and levels of medical institutions in China according to a unified protocol of bedside surveys and case investigations.Results In 2024,a total of 5 736 medical institutions and 2 751 765 patients were surveyed.Among them,34 889 HAI cases were identified,with a prevalence rate of 1.27％.The number of HAI episodes was 38 032,and case prevalence rate was 1.38％.The prevalence rate of HAI in medical institutions in different regions of China ranged from 0.66％to 2.35％.Among medical institutions of different scales,those with a bed capacity of ≥900 had the high-est incidence of HAI,reaching 1.65％.The most common infection site was the lower respiratory tract(44.66％),followed by the urinary tract(12.94％),surgical site(9.32％),upper respiratory tract(7.02％),and bloodstream infection(5.78％).The top 3 departments with the highest HAI rates were the general intensive care unit(10.02％),department of neurosurgery(5.51％),and department(group)of hematology(5.34％).A total of 23 238 strains of HAI pathogens were detected,with 10 714 strains(46.10％)from lower respiratory tract speci-mens.The top 5 detected strains were Klebsiella pneumoniae(14.76％),Pseudomonas aeruginosa(13.33％),Escherichia coli(12.79％),Acinetobacter baumannii(9.23％),and Staphylococcus aureus(7.88％).231 944 pa-tients underwent class Ⅰ incision surgery were monitored,with 1 647 cases experienced surgical site infection,and the prevalence rate of surgical site infection was 0.71％.The number of patients who should undergo pathogen de-tection(patients receiving therapeutic and therapeutic combined prophylactic antimicrobial agents)was 715 179,while the actual number was 480 492,with a pathogen detection rate of 67.18％.425 225 patients received patho-genic detection before treatment,with a detection rate of 59.46％.Conclusion The overall HAI prevalence in Chi-na is lower,showing disparities among medical institutions of different regions and scales.Therefore,precise imple-mentation of measures is necessary for HAI prevention and control,with a focus on high-risk institutions and high-risk departments,key areas,and critical procedures.All levels of medical institutions should continuously reduce the incidence of HAI by strengthening monitoring,standardizing the use of antimicrobial agents,and reinforcing basic HAI prevention and control measures.

Objective To understand the current situation of healthcare-associated infection(HAI)in China,pro-vide data support and decision-making basis for formulating scientific and effective strategies for HAI prevention and control.Methods A nationwide cross-sectional survey on HAI was conducted among various types and levels of medical institutions in China according to a unified protocol of bedside surveys and case investigations.Results In 2024,a total of 5 736 medical institutions and 2 751 765 patients were surveyed.Among them,34 889 HAI cases were identified,with a prevalence rate of 1.27％.The number of HAI episodes was 38 032,and case prevalence rate was 1.38％.The prevalence rate of HAI in medical institutions in different regions of China ranged from 0.66％to 2.35％.Among medical institutions of different scales,those with a bed capacity of ≥900 had the high-est incidence of HAI,reaching 1.65％.The most common infection site was the lower respiratory tract(44.66％),followed by the urinary tract(12.94％),surgical site(9.32％),upper respiratory tract(7.02％),and bloodstream infection(5.78％).The top 3 departments with the highest HAI rates were the general intensive care unit(10.02％),department of neurosurgery(5.51％),and department(group)of hematology(5.34％).A total of 23 238 strains of HAI pathogens were detected,with 10 714 strains(46.10％)from lower respiratory tract speci-mens.The top 5 detected strains were Klebsiella pneumoniae(14.76％),Pseudomonas aeruginosa(13.33％),Escherichia coli(12.79％),Acinetobacter baumannii(9.23％),and Staphylococcus aureus(7.88％).231 944 pa-tients underwent class Ⅰ incision surgery were monitored,with 1 647 cases experienced surgical site infection,and the prevalence rate of surgical site infection was 0.71％.The number of patients who should undergo pathogen de-tection(patients receiving therapeutic and therapeutic combined prophylactic antimicrobial agents)was 715 179,while the actual number was 480 492,with a pathogen detection rate of 67.18％.425 225 patients received patho-genic detection before treatment,with a detection rate of 59.46％.Conclusion The overall HAI prevalence in Chi-na is lower,showing disparities among medical institutions of different regions and scales.Therefore,precise imple-mentation of measures is necessary for HAI prevention and control,with a focus on high-risk institutions and high-risk departments,key areas,and critical procedures.All levels of medical institutions should continuously reduce the incidence of HAI by strengthening monitoring,standardizing the use of antimicrobial agents,and reinforcing basic HAI prevention and control measures.

SWOT-PEST model was used to analyze the internal advantages and disadvantages,external,opportunities and challenges of tertiary public pediatric hospitals.Based on stakeholder theory,through the literature review method,policy analysis method,combined with the actual work,and summarize its main role and demands.Put forward the development strategy of three-level public pediatric specialty hospital.Through the analysis of interest demands of stakeholders of tertiary public pediat-ric specialty hospitals,the overall development is good at present,but there are still problems that need to be solved urgently.From the perspective of internal and external stakeholders,the optimization strategy involving multiple levels,multiple angles and multiple subjects is proposed to promote the comprehensive development of tertiary public pediatric specialty hospitals.

Objective:To establish a method for determintation of chlorogenic acid and linarin in Yejuhua granules by HPLC.Methods:We applied HPLC methods. The Kromasil 100-5 C18 column (250 mm×4.6 mm,5 μm) was used, the mobile phase was acetonitrile-0.4%H 3PO 4 solution (gradient elution), the flow rate was 1.0 ml/min, the dection wavelenghth was 334 nm and the column temperture was 32 ℃. Results:Chlorogenic acid and buddleoside had good linearity in the ranges of 0.30-1.50 μg ( r2=0.999 1) and 0.12-0.62 μg ( r2=0.999 8), respectively. The average recoveries were 99.70% and 96.67%, with RSD<2%, respectively. Conclusion:The method is simple, rapid, reliable, efficient, and can be used for determination of chlorogenic acid and buddleoside in Yejuhua Granules.

Objective To explore the curative effect of stereotactic radiotherapy combined with transcatheter arterial chemoembolization (TACE) for patients with hepatic metastases of colorectal cancer and influence on the expressions of omentin-1 and angiopoietin-2 (Ang-2).Methods A total of 90 patients with hepatic metastases of colorectal cancer from December 2013 to December 2015 in our hospital were selected as the research objects.Patients were divided into observation group and control group according to random number table method with 45 cases respectively.Patients in control group were treated with TACE,and patients in observation group were treated with stereotactic radiotherapy combined with TACE.After treatment,the clinical efficacy,expression levels of plasma omentin-1 and Ang-2,score of quality of life and adverse reaction were compared in the two groups.Results The objective response rate in observation group (82.2％) was significantly higher than that in control group (60.0％),and the difference was statistically significant (x2 =5.409,P =0.020).After treatment,the omentin-1 and Ang-2 expression levels in observation group were lower than those in control group [(43.7 ± 18.1) ng/ml vs.(52.1 ± 17.9) ng/ml,t =2.214,P =0.029;(2.0 ±0.2) g/L vs.(2.3 ± 0.3) g/L,t =6.028,P ＜ 0.001].The score of quality of life in observation group was significantly higher than that in control group [(87.6 ± 11.2) vs.(68.7 ± 10.3)],and the difference was statistically significant (t =8.332,P ＜ 0.001).There were no differences on the adverse reaction rates such as abnormal liver function (35.6％ vs.42.2％,x2 =0.421,P =0.517),nausea and vomiting (44.4％ vs.37.8％,x2 =0.413,P=0.520),skin injury (6.7％ vs.0,x2 =3.101,P=0.078) and fever (35.6％ vs.31.1％,x2 =0.202,P =0.655) between the two groups.Conclusion The implementation of stereotactic radiotherapy combined with TACE in the treatment of hepatic metastases of colorectal cancer is a safety and effective method.It can significantly reduce the expression levels of plasma omentin-1 and Ang-2,inhibit of tumor angiogenesis,and improve the quality of life of patients.

OBJECTIVE:To provide evidence for strengthening education and training before clinical practice and employment guidance among pharmacy junior students of our university. METHODS:Anonymous questionnaire survey was conducted for our university. Questionnaire survey included student employment intention and internship units,relationship of internships with employ-ment,the tendency of employment after graduation,personal attitude about pharmaceutical professional development prospect,ex-pected monthly income in the first year of their career,etc. RESULTS:Totally 71 questionnaires were sent out,71 were effectively received. Among all respondents,74.3%(52 students)believed employment intention had great relationship with internship units;24.3%(17 students)thought employment intention had not great relationship with internship units;moreover,one student thought employment intention had no any relationship with internship units. Most students(94.3%,66 students)with good attitude on in-ternships believed it could accumulate work experience;32.9%(23 students) thought they could stay in the internship unit after practice;moreover,17.1%(12 students) believed practice had little effect on employment. Among them,94.0%(63 students) tended to be employed after graduation,and only 6.0% chose a graduate school to continue their studies. Among the students who chose employment after graduation,76.1%(51 students)tended to engage in pharmaceutical related work,while 17.9%(12 stu-dents) tended to be engaged in work nothing to do with pharmacy or self-employed. The majority (69.6%,48 students) believed that pharmaceutical major prospect was general and pharmaceutical major development varied from person to person;17.4%(12 students)thought pharmaceutical major had good prospect and was promising;13.0%(9 students)believed that pharmaceutical ma-jor had no good prospect and didn't know its prospect. Most of the students(78.2%,54 students)expected a monthly income of 2500-5000 yuan in the first year of their career;18.9%expected a monthly income more than 5000 yuan(13 students);the minor-ity expected a monthly income of 1500-2500 yuan or more than 8000 yuan. CONCLUSIONS:The view of students on internship and employment have a certain gap with the social situation. Related departments of colleges and universities need to adjust the thought of students and strengthen guidance.