ObjectiveTo study the chemical constituents of Painong powder and the constituents absorbed into blood after oral administration to rats by ultra performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry （UPLC-Q-Orbitrap-MS）. MethodsUPLC-Q-Orbitrap-MS was employed for mass spectrometry data acquisition. The chemical constituents of Painong Powder and the constituents absorbed into blood were characterized and identified via Xcalibur 4.2 and Compound Discoverer v3.3.1 （CD） based on retention time， accurate molecular weights， secondary fragmentation ions， and comparison with reference standards and literature reports. ResultsA total of 176 chemical compounds， including 56 flavonoids， 42 triterpenoid saponins， 23 monoterpenes， 7 coumarins， 5 tannins， and other 43 compounds were identified from Painong powder. 49 components were identified in the rat plasma after oral administration of Painong powder， including 33 prototype constituents and 16 metabolites. The major metabolic pathways included hydrolysis in phase Ⅰ metabolic reactions， as well as methylation， sulfation， and glucuronidation in phase Ⅱ metabolic reaction. ConclusionThe method comprehensively identified the chemical constituents of Painong powder both in vitro and in vivo， and may provide a reference for the study of quality control and clinical applications.

BACKGROUND/OBJECTIVES: Unhealthy diets are associated with chronic stress. An allostatic load (AL) is a comprehensive physiological index that measures the chronic stress response of the body. As a healthy dietary pattern, the role of Dietary Approaches to Stop Hypertension (DASH) in the development of an AL during pregnancy remains unclear. This study examined the relationship between the DASH dietary pattern and AL during pregnancy. SUBJECTS/METHODS: This study was a prospective study. From January 2024 to November 2024, 134 pregnant women in the second trimester (23–27 weeks) and third trimester (32–36 weeks) of pregnancy who met the inclusion and exclusion criteria in the obstetrics clinic of a tertiary general hospital in Anhui Province were selected for a questionnaire survey, physical examination, and laboratory examination. The DASH dietary pattern was assessed using the DASH scoring tool, and the total AL score was calculated using nine biomarkers that represent the cardiovascular, metabolic, and immune systems. Logistic regression was used to analyze the relationship between the DASH score and AL. RESULTS: One hundred and thirty-four pregnant women were included in this study. At the second and third trimesters, 41.8% and 37% of pregnant women, respectively, were in the high AL group. The binary logistic regression results showed that the DASH score was negatively correlated with the AL in the unadjusted model (odds ratio [OR], 0.878; 95% confidence interval [CI], 0.807–0.957; P = 0.003) and adjusted model (OR, 0.878; 95% CI, 0.792–0.973; P = 0.013) in the second trimester, the DASH score was negatively correlated with the AL in the unadjusted model (OR, 0.832; 95% CI, 0.758–0.913; P < 0.001) and adjusted model (OR, 0.806; 95% CI, 0.716–0.908; P < 0.001) in the third trimester. CONCLUSION The DASH score was negatively correlated with the AL in pregnant women.A low DASH score may increase the risk of a high AL, which may have adverse effects on physical and mental health.

Objective: To evaluate the effectiveness of a family-school collaborative intervention on sleep health among fifth-grade primary school students, so as to provide scientific evidence for promoting sleep health among primary school students. Methods: From April to June 2024, a baseline survey was conducted on 342 fifth-grade students and their parents from one primary school in a district of Beijing, using the convenient sampling method. A semester of sleep health education was implemented from September to December 2024, covering cognitive, behavioral and environmental factors that affected timely bedtime; and the program took various forms, including student courses, popular-science articles for parents, and personalized feedback reports. Another primary school in the same area was conveniently selected as the control group, where 313 fifth-grade students and their parents received routine health education. The subjects were assessed for their baseline and end-point (March to June 2025) sleep conditions using sleep diaries (222 participants in the intervention group and 225 in the control group) and accelerometers (120 participants in the intervention group and 88 in the control group), respectively. The independent samples t-test and the Wilcoxon rank-sum test were used to compare characteristics between groups，and linear mixed models were employed to evaluate the intervention effects. Results: In the sleep diary evaluation, the intervention group had an earlier weekend wake up time and a smaller social jetlag than the control group at baseline ( t/Z =3.42, 7.21); in the accelerometer evaluation, the intervention group exhibited a smaller social jetlag than the control group at baseline ( Z =3.90) (all P <0.05). In the sleep diary evaluation, compared with the control group, the intervention group showed a reduced pre-to-post change in school-day bedtime ( β = -6.70), whereas the pre-to-post changes in school-day sleep duration, weekend wake-up time, weekend sleep duration, and average sleep duration were all increased at baseline and at the end ( β =8.41, 22.58, 27.03,13.74) (all P <0.05). In the accelerometer evaluation, compared with the control group, the intervention group showed reduced pre-to-post changes in school-day sleep onset time and school-day wake time ( β =-14.75, -6.24), whereas the pre-to-post change in school-day sleep duration increased at baseline and at the end ( β =8.01) (all P <0.05). Conclusion A family-school collaborative sleep health intervention may be an effective strategy for improving sleep among fifth-grade primary school students.

In order to integrate clinical data, image data, and omics data scattered across different systems, and effectively support clinical research based on real-world data, a hospital has integrated Hadoop big data processing technology with distributed parallel database technology to build a data storage and calculation system that integrates lakes and warehouses. Through the integration of 15 medical information system data, data governance based on patient master indexes, and the design and development of an application platform that covered 8 major functions and integrated general scientific research and specialized disease applications, the hospital has built an integrated scientific research big data platform, which included 3.3 billion pieces of data from 20.26 million patients and 98.57 million visits, and has built 3 specialized disease databases. From January to August 2024, it has supported data extraction and analysis for 35 research projects, reducing traditional code-based data retrieval time from 5-45 workdays to several hours or even minutes, significantly enhancing the efficiency of clinical research.

Objective To analyze the distribution characteristics of 13 common respiratory pathogens in children in Zibo area from 2020 to 2022.Methods A total of 3091 hospitalized children with respiratory infections admitted to Zibo Maternal and Child Health Hospital from January 2020 to December 2022 were selected as the subjects.Throat swabs or bronchoalveolar lavage fluid samples were collected from the patients,and 13 common respiratory pathogens were tested to analyze the distribution differences among different genders,ages,and seasons.Results Among 3091 pediatric patients,1794 were found to be infected with pathogens.The top three pathogens were Mycoplasma pneumoniae,rhinovirus,and respiratory syncytial virus(RSV).The single infection rate was 47.75％,while the mixed infection rate was 10.28％,with the most common scenario being a mixed infection of two pathogens.There were statistically significant differences in the pathogen profiles across different age groups(P＜0.001):infants had the highest detection rate of RSV,young children were primarily infected with rhinovirus,preschool and school-age children were predominantly infected with Mycoplasma pneumoniae.Seasonal distribution showed that the highest positive rate was in autumn,while the lowest was in spring(P＜0.05).In spring,the main pathogens were rhinovirus and Mycoplasma pneumoniae;in summer,they were rhinovirus and parainfluenza virus;in autumn,they were Mycoplasma pneumoniae and RSV;and in winter,the detection rates of Mycoplasma pneumoniae and influenza B virus were higher.Conclusion From 2020 to 2022,Mycoplasma pneumoniae,rhinovirus and RSV were the main pathogens of children's respiratory tract infection in Zibo area,and there were significant differences in the distribution of pathogens among different ages and seasons.

BACKGROUND:Macrophages are an important part of innate immunity.When the internal environment of the body changes,macrophages can produce different polarization phenotypes and play the corresponding inflammatory immune function.Mesenchymal stem cells can secrete a large number of extracellular vesicles into the internal environment of the body,which have the functions of intercellular signaling and immune regulation.Studies have shown that mesenchymal stem cells and mesenchymal stem cells-extracellular vesicles can affect the M1/M2 polarization balance of macrophages so as to treat immune inflammatory diseases.OBJECTIVE:To explore the signaling mechanism of how mesenchymal stem cells and their extracellular vesicles interfere with autoimmune diseases by regulating the polarization of macrophages,as well as the related research progress of engineered extracellular vesicles in this field.METHODS:The first author searched the relevant literature published in PubMed,CNKI and other databases until June 2024.Chinese search terms were"mesenchymal stem cells,extracellular vesicles,exosomes,apoptotic bodies,apoptotic vesicles,macrophage polarization,M1 polarization,M2 polarization,autoimmune diseases,multiple sclerosis,rheumatoid arthritis,systemic lupus erythematosus,type 1 diabetes mellitus,inflammatory bowel disease,autoimmune dacryadenitis,engineered extracellular vesicles,engineering exosomes,drug delivery."English search terms were"macrophage polarization,M1 macrophage,M2 macrophage,autoimmune disease,type 1 diabetes,multiple sclerosis,rheumatoid arthritis,systemic lupus erythematosus,autoimmune dacryadenitis,inflammatory bowel disease,mesenchymal stem cells,extracellular vesicles,engineered extracellular vesicles,engineering exosomes,drug delivery."The title and abstract of each paper were read and initially screened.Finally,70 articles were selected for induction and analysis.RESULTS AND CONCLUSION:(1)Mesenchymal stem cells can regulate M1/M2 polarization by releasing or indirectly acting on functional proteins.(2)Mesenchymal stem cells can regulate macrophage M2 polarization through inflammasome.(3)Mesenchymal stem cells can be combined with commonly used drugs to enhance drug efficacy.(4)Mesenchymal stem cells can regulate the release of mesenchymal stem cells-extracellular vesicles after inflammatory stimulation and affect the polarization of macrophages.(5)Mesenchymal stem cells-extracellular vesicles can regulate autoimmune diseases by targeting macrophage polarization through PTEN,NOTCH,nuclear factor κB,Toll-like receptors,PI3K/AKT and other pathways.(6)Engineered extracellular vesicles can achieve non-invasive targeted drug delivery,prolong the half-life of drugs,promote the oral administration of exosomes,reduce allograft reaction,improve the bioavailability of Chinese herbs and overcome the blood-brain barrier,opening up a new path for drug delivery.

OBJECTIVE To establish a combined pharmacokinetic(PK)-pharmacodynamic(PD)model for knee osteoarthritis(KOA)of crossbow drug microemulsion multi-components(benzoylmesaconine,benzoylhypacoitine,mesaconitine,periplocin,neo-chlorogenic acid,vanillic acid,chlorogenic acid),and elucidate the dynamic changes in the KOA rats and the interrelation with the e-lapsed efficacy of the drug.METHODS A KOA rat model was induced by 4%papain;the PK process of crossbow medicine microe-mulsion components in rat synovial fluid was analyzed by UPLC to establish a PK model;the contents of MMP-3,MMP-13,TNF-α and IL-1β in KOA rats at different time points after administration were determined by ELISA analysis to establish a PD model;Phoe-nix WinNonlin software was used to fit the PK and PD data to obtain a PK-PD model.RESULTS PK results showed that the multi-components of the microemulsion were slowly absorbed in the joint cavity and gradually reached the peak value within 3-5 h.The Cmax of benzoylmesaconine,benzoylhypacoitine mesaconitine,periplocoside,neochlorogenic acid,vanillic acid and chlorogenic acid were 1.23,1.48,1.62,4.67,0.93,1.25 and 2.35 μg·mL-1,respectively;the area under the drug-time curve(AUC0-11)was 2.58,4.04,3.54,12.15,2.51,2.41 and 4.11 h·μg·mL-1,respectively.PD results showed that at different time points after adminis-tration,the contents of MMP-3,IL-1β,TNF-α,and MMP-13 decreased to varying degrees,among which MMP-3 decreased insig-nificantly,with significant differences only at 6 h;the contents of the remaining IL-1β,TNF-α,and MMP-13 decreased significantly(P<0.05,P<0.01),and showed the phenomenon of lagged efficacy;the PK-PD binding model showed that the drug concentration of the multi-component drug in the crossbow medicine microemulsion could be well fitted with its drug efficacy data.CONCLUSION The established PK-PD binding model can predict the drug efficacy changes after administration,and provides a corresponding refer-ence for the crossbow medicine microemulsion treatment of KOA.

Objective To examine the changing prevalence and antimicrobial resistance profiles of Burkholderia cepacia in 52 hospitals across China from 2015 to 2021.Methods A total of 9 261 strains of B.cepacia were collected from 52 hospitals between January 1,2015 and December 31,2021.Antimicrobial susceptibility of the strains was tested using Kirby-Bauer method or automated antimicrobial susceptibility testing systems according to a unified protocol.The results were interpreted according to the breakpoints released in the Clinical & Laboratory Standards Institute(CLSI)guidelines(2023 edition).Results A total of 9 261 strains of B.cepacia were isolated from all age groups,especially elderly patients.The proportion was 11.1％(1 032 strains)in children,significantly lower than the proportion in adults.About half(46.5％,4 310/9 261)of the strains were isolated from patients at least 60 years old and 42.3％(3 919/9 261)of the strains were isolated from young adults.Most isolates(71.1％)were isolated from sputum and respiratory secretions,followed by urine(10.7％)and blood samples(8.1％).B.cepacia isolates were highly susceptible to the five antimicrobial agents recommended in the CLSI M100 document(33rd edition,2023).B.cepacia isolates showed relatively higher resistance rates to meropenem and levofloxacin.However,the resistance rates to ceftazidime,trimethoprim-sulfamethoxazole,and minocycline remained below 8.1％.The percentage of B.cepacia strains resistant to levofloxacin was the highest compared to other antibiotics in any of the three age groups(from 12.4％in the patients＜18 years old to 20.6％in the patients aged 60 years or older).Conclusions B.cepacia is one of the clinically important non-fermenting gram-negative bacteria.Accurate and timely reporting of antimicrobial susceptibility test results and ongoing antimicrobial resistance surveillance are helpful for rational prescription of antimicrobial agents and proper prevention and control of nosocomial infections.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.