ObjectiveTo evaluate the anti-inflammatory activity of the novel magnolol ester derivative YW and to investigate its effects on chondrocyte senescence and preliminary mechanisms. MethodsMagnolol and p-methylbenzoic acid were used as raw materials to synthesize the magnolol ester derivative YW （Molecular Formula： C₂₆H₂₄O₃， Molecular Weight： 384.17， HPLC Purity >96%） via DCC/DMAP-catalyzed esterification. Cytotoxicity was assessed using the CCK-8 assay. A lipopolysaccharide （LPS）-induced RAW264.7 macrophage activation model and an interleukin-1β （IL-1β）-induced rat primary chondrocyte model were established. The release and mRNA expression of inflammatory factors including nitric oxide （NO）， IL-1β， tumor necrosis factor-alpha （TNF-α）， and IL-6 were detected by enzyme-linked immunosorbent assay （ELISA）， Griess reagent method， and quantitative real-time PCR （RT-qPCR）. The expression of senescence markers such as inducible nitric oxide synthase （iNOS）， pro-interleukin-1β （pro-IL-1β）， lysine acetyltransferase 7 （KAT7）， cyclin-dependent kinase inhibitor 1A （p21）， and cyclin-dependent kinase inhibitor 2A （p16）， as well as proteins related to chondrocyte extracellular matrix synthesis and catabolism， were analyzed by Western blot （WB）. Molecular docking was performed using Discovery Studio 2019 to validate target binding. ResultsYW exhibited no significant cytotoxicity at concentrations ≤20 μmol/L. YW concentration-dependently inhibited LPS-induced macrophage inflammatory cytokine release， significantly downregulated iNOS， Pro-IL-1β protein， and inflammatory cytokine mRNA expression （P<0.01）. YW stably bound to KAT7 protein （binding energy： -94.2 kcal/mol）； YW downregulated KAT7 and aging marker protein expression in naturally aged and IL-1β-induced chondrocyte models （P<0.01）； YW regulated chondrocyte matrix synthesis and catabolic protein expression in IL-1β-induced chondrocytes （P<0.01）. ConclusionYW inhibits macrophage activation and inflammatory cytokine release while downregulating KAT7 and senescence marker protein expression in chondrocytes， thereby blocking chondrocyte senescence.

Objective To analyze the cellular and histopathological characteristics of underdiagnosed thyroid nodules of Chinese thyroid imaging reporting and data system(C-TIRADS) categories 3 and 4a,thus improving the understanding of these lesions. Methods The data of ultrasound and fine needle aspiration cytology were collected from 683 nodules diagnosed based on pathological evidence in 549 patients undergoing thyroid surgery.The cellular and histopathological characteristics of C-TIRADS 3 and 4a nodules were analyzed. Results Two hundred and sixty-eight nodules were classified as C-TIRADS category 3,including 236 benign nodules,12 low-risk ones,and 20 (7.46%) malignant ones.Two hundred and twenty-one nodules were classified as C-TIRADS category 4a,including 133 benign nodules,7 low-risk ones,and 81 (36.65%) malignant ones.The malignancy rates differed between C-TIRADS 3 and 4a nodules (χ²=58.93,P<0.001),and both were higher than the recommended malignancy rate in the guidelines for malignancy risk stratification of thyroid nodules (C-TIRADS) (both P<0.001).According to the pathological evidence,the underdiagnosed C-TIRADS 3/4a nodules were mainly papillary thyroid carcinoma,especially in patients with Hashimoto thyroiditis.There was not a consistent one-to-one match between each ultrasound result and each cytological classification of low-risk thyroid nodules.Conclusions When the malignant features in preoprative ultrasound imaging are atypical or absent,papillary thyroid carcinoma (especially with Hashimoto thyroiditis),follicular carcinoma,and medullary carcinoma are likely to be underdiagnosed as C-TIRADS 3 or 4a nodules.Therefore,efforts should be made to fully understand the cellular and pathological characteristics of these lesions.
Humans ; Thyroid Nodule/diagnostic imaging* ; Female ; Male ; Middle Aged ; Adult ; Ultrasonography ; Biopsy, Fine-Needle ; Aged ; Young Adult ; Thyroid Neoplasms/diagnostic imaging* ; Adolescent

Objective To evaluate the reliability and validity and perform cost-consequence analysis of the brief version of the Montreal cognitive assessment(MoCA)for identifying cognitive impairment in a community-based population ≥50 years of age.Methods The internal consistency and retest reliability of the brief version of the MoCA were analyzed,and the area under the curve(AUC),sensitivity,and specificity were determined to discriminate mild cognitive impairment(MCI)and dementia with the clinical dementia rating(CDR)as the diagnostic criterion.The consistency between the brief version and the full version was analyzed by the Kappa test and the Bland-Altman method,and the number of individuals entering the diagnostic assessment and the overall assessment time were estimated and compared between the two versions.Results A total of 303 individuals were included in this study,of whom 192,94,and 17 had normal cognitive function,MCI,and dementia,respectively.The Cronbach's α and re-test coefficients of the brief version of MoCA were 0.754 and 0.711(P<0.001),respectively.The brief version showed the AUC,sensitivity,and specificity of 0.889,74.5%,and 93.8% for identifying MCI,and 0.994,100%,and 93.8% for identifying dementia,respectively.When the brief version of MoCA was used to identify 94 patients with MCI in 303 individuals,107 individuals required additional diagnostic assessment,with an overall assessment time of 142.4 h,which represented decreases of 21.3% and 32.7%,respectively,compared with those of the full version.When the brief version of MoCA was used to identify 17 patients with dementia in 303 individuals,35 individuals required additional diagnostic assessment,with an overall assessment time of 70.4 h,a decrease of 29.5% in the time cost compared with the full version.Conclusions The brief version of MoCA can identify cognitively impaired individuals in a community-based middle-aged and elderly population,with diagnostic validity comparable to that of the full version but less time cost and fewer individuals needing additional diagnostic assessment to detect true-positive cases.It could be expanded for use in the community-based primary screening setting.
Humans ; Aged ; Middle Aged ; Cognitive Dysfunction/diagnosis* ; Male ; Female ; Mental Status and Dementia Tests ; Reproducibility of Results ; Dementia/diagnosis* ; Sensitivity and Specificity ; Aged, 80 and over ; Cost-Benefit Analysis

Objective:To understand the potential characteristics of decision-making preparation in outpatient hypertensive patients based on latent profile analysis, to identify the influencing factors of different categories of decision-making preparation levels, and to explore the performance of different decision-making preparation types in facilitation of patients involvement in treatment decision-making.Methods:Through a cross-sectional study, 350 hypertensive patients attending outpatient clinics in five different types of healthcare institutions (general hospitals, specialised hospitals and community hospitals) in Tianjin during January to May 2024 who met the inclusion and exclusion criteria were selected by the convenience sampling method as study subjects. General Information Questionnaires, Preparation for Decision Making Scale, and Facilitation of Patient Involvement Scale were used for investigation.Results:Totally 350 valid questionnaires [178 males and 172 females aged 25-89(57.24 ± 13.39)years old] were collected. The decision-making preparation score of outpatient hypertensive patients was (64.19 ± 18.69). The latent profile analysis results showed that the decision-making preparation of outpatient hypertensive patients could be divided into three potential categories: decision-making information scarcity type accounted for 20.0%(70/350), decision-making balance negotiation type accounted for 39.7%(139/350), and decision-making preparation adequacy type accounted for 40.3%(141/350). The results of multiple Logistic regression analysis showed that age, medical insurance type, occupation, and children′s condition were the influencing factors for the potential categories of decision-making preparation in outpatient hypertensive patients (all P<0.05). Age [less than 35 years old: OR(95% CI)=0.127(0.020-0.796)], occupation [on the job: OR(95% CI)=2.010 (1.034-3.906)], were the influencing factors of decision-making balance negotiation group (all P<0.05). Medical insurance type [basic medical insurance for urban employees: OR(95% CI)=0.372(0.193-0.720)], occupation [on the job: OR(95% CI)=2.500(1.270-4.920)], children′s condition[junior and senior high school: OR(95% CI)=0.391(0.190-0.802)] were the influencing factors of decision-making preparation adequacy group (all P<0.05). Conclusions:The level of promoting patient participation among outpatients with hypertension is relatively high, and there are differences in the perceived degree of promoting patient participation among patients with different types of decision preparation.It is recommended that medical staff provide decision-making related information based on the characteristics of different decision-making preparation categories of patients, encourage patients to actively participate in decision-making, and construct targeted decision support plans.

Objective:To analyze the effect of altitude on NIH-CPSI score in patients with chronic prostatitis/chronic pelvic pain syndrome(CP/CPPS)Methods:Clinical data and the results of NIH-CPSI Questionnaire of the 321 patients with CP/CPPS at different altitudes were collected from March 2021 to March 2022.And the influence of altitudes on NIH-CPSI score of CP/CPPS was analyzed.Result:The NIH-CPSI score of patients living at an altitude of 4 300 m was significantly higher than that of patients living at an altitude of 1 500 m and 2 200 m.The CP/CPPS patients who lived in the higher altitude had more severe symptoms of pain and urination as well as lower scores of life quality(P＜0.05).Conclusion:NIH-CPSI score increased significantly with higher alti-tude,indicating more severe symptoms and decreased quality of life in CP/CPPS patients.These findings highlight the need for man-agement strategies for specific heights in patients with CP/CPPS.

Objective To investigate the distribution and antimicrobial resistance profiles of clinically isolated Haemophilus influenzae and Moraxella catarrhalis in hospitals across China from 2015 to 2021,and provide evidence for rational use of antimicrobial agents.Methods Data of H.influenzae and M.catarrhalis strains isolated from 2015 to 2021 in CHINET program were collected for analysis,and antimicrobial susceptibility testing was performed by disc diffusion method or automated systems according to the uniform protocol of CHINET.The results were interpreted according to the CLSI breakpoints in 2022.Beta-lactamases was detected by using nitrocefin disk.Results From 2015 to 2021,a total of 43 642 strains of Haemophilus species were isolated,accounting for 2.91％of the total clinical isolates and 4.07％of Gram-negative bacteria in CHINET program.Among the 40 437 strains of H.influenzae,66.89％were isolated from children and 33.11％were isolated from adults.More than 90％of the H.influenzae strains were isolated from respiratory tract specimens.The prevalence of β-lactamase was 53.79％in H.influenzae strains.The H.influenzae strains isolated from children showed higher resistance rate than the strains isolated from adults.Overall,779 strains of H.influenzae did not produce β-lactamase but were resistant to ampicillin(BLNAR).Beta-lactamase-producing strains showed significantly higher resistance rates to these antimicrobial agents than the β-lactamase-nonproducing strains.Of the 16 191 M.catarrhalis strains,80.06％were isolated from children and 19.94％isolated from adults.M.catarrhalis strains were mostly susceptible to both amoxicillin-clavulanic acid and cefuroxime,evidenced by resistance rate lower than 2.0％.Conclusions The emergence of antibiotic-resistant H.influenzae due to β-lactamase production poses a challenge for clinical anti-infective treatment.Therefore,it is very important to implement antibiotic resistance surveillance for H.influenzae and guide rational antibiotic use.All local clinical microbiology laboratories should actively improve antibiotic susceptibility testing and strengthen antibiotic resistance surveillance for H.influenzae.

Objective To understand the changing composition and antibiotic resistance of bacterial species in the clinical isolates from outpatient and emergency department(hereinafter referred to as outpatients)and inpatient children over time in various hospitals,and to provide laboratory evidence for rational antibiotic use.Methods The data on clinically isolated pathogenic bacteria and antimicrobial susceptibility of isolates from outpatients and inpatient children in the CHINET program from 2015 to 2021 were collected and analyzed.Results A total of 278 471 isolates were isolated from pediatric patients in the CHINET program from 2015 to 2021.About 17.1％of the strains were isolated from outpatients,primarily group A β-hemolytic Streptococcus,Escherichia coli,and Staphylococcus aureus.Most of the strains(82.9％)were isolated from inpatients,mainly SS.aureus,E.coli,and H.influenzae.The prevalence of methicillin-resistant S.aureus(MRSA)in outpatients(24.5％)was lower than that in inpatient children(31.5％).The MRSA isolates from outpatients showed lower resistance rates to the antibiotics tested than the strains isolated from inpatient children.The prevalence of vancomycin-resistant Enterococcus faecalis or E.faecium and penicillin-resistant S.pneumoniae was low in either outpatients or inpatient children.S.pneumoniae,β-hemolytic Streptococcus and S.viridans showed high resistance rates to erythromycin.The prevalence of erythromycin-resistant group A β-hemolytic Streptococcus was higher in outpatients than that in inpatient children.The prevalence of β-lactamase-producing H.influenzae showed an overall upward trend in children,but lower in outpatients(45.1％)than in inpatient children(59.4％).The prevalence of carbapenem-resistant Klebsiella pneumoniae(CRKpn),carbapenem-resistant Pseudomonas aeruginosa(CRPae)and carbapenem-resistant Acinetobacter baumannii(CRAba)was 14％,11.7％,47.8％in outpatients,but 24.2％,20.6％,and 52.8％in inpatient children,respectively.The prevalence of multidrug-resistant E.coli,K.pneumoniae,Proteus mirabilis,P.aeruginosa and A.baumannii strains was lower in outpatients than in inpatient children.The prevalence of fluoroquinolone-resistant E.coli,ESBLs-producing K.pneumoniae,ESBLs-producing P.mirabilis,carbapenem-resistant E.coli(CREco),CRKpn,and CRPae was lower in children in outpatients than in inpatient children,but the prevalence of CRAba in 2021 was higher than in inpatient children.Conclusions The distribution of clinical isolates from children is different between outpatients and inpatients.The prevalence of MRSA,ESBL,and CRO was higher in inpatient children than in outpatients.Antibiotics should be used rationally in clinical practice based on etiological diagnosis and antimicrobial susceptibility test results.Ongoing antimicrobial resistance surveillance and prevention and control of hospital infections are crucial to curbing bacterial resistance.

Objective To investigate the changing antibiotic resistance profiles of E.coli isolated from patients in the 52 hospitals participating in the CHINET program from 2015 to 2021.Methods Antimicrobial susceptibility was tested for clinical isolates of E.coli according to the unified protocol of CHINET program.WHONET 5.6 and SPSS 20.0 software were used for data analysis.Results Atotal of 289 760 nonduplicate clinical strains ofE.coli were isolated from 2015 to 2021,mainly from urine samples(44.7±3.2)％.The proportion of E.coli strains isolated from urine samples was higher in females than in males(59.0％vs 29.5％).The proportion of E.coli strains isolated from respiratory tract and cerebrospinal fluid samples was significantly higher in children than in adults(16.7％vs 7.8％,0.8％vs 0.1％,both P＜0.05).The isolates from internal medicine department accounted for the largest proportion(28.9±2.8)％with an increasing trend over years.Overall,the prevalence of ESBLs-producing E.coli and carbapenem resistant E.coli(CREco)was 55.9％and 1.8％,respectively during the 7-year period.The prevalence of ESBLs-producing E.coli was the highest in tertiary hospitals each year from 2015 to 2021 compared to secondary hospitals.The prevalence of CREco was higher in children's hospitals compared to secondary and tertiary hospitals each year from 2015 to 2021.The prevalence of ESBLs-producing E.coli in tertiary hospitals and children's hospitals and the prevalence of CREco in children's hospitals showed a decreasing trend over the 7-year period.The prevalence of CREco in secondary and tertiary hospitals increased slowly.Antibiotic resistance rates changed slowly from 2015 to 2021.Carbapenem drugs(imipenem,meropenem)were the most active drugs amongβ-lactams against E.coli(resistance rate≤2.1％).The resistance rates of E.coli to β-lactam/β-lactam inhibitor combinations(piperacillin-tazobactam,cefoperazone-sulbactam),aminoglycosides(amikacin),nitrofurantoin and fosfomycin(for urinary isolates only)were all less than 10％.The resistance rate of E.coli strains to antibiotics varied with the level of hospitals and the departments where the strains were isolated,especially for cefazolin and ciprofloxacin,to which the resistance rate of E.coli strains from children in non-ICU departments was significantly lower than that of the strains isolated from other departments(P＜0.05).The E.coli isolates from ICU showed higher resistance rate to most antimicrobial agents tested(excluding tigecycline)than the strains isolated from other departments.The E.coli strains isolated from tertiary hospitals showed higher resistance rates to the antimicrobial agents tested(excluding tigecycline,polymyxin B,cefepime and carbapenems)than the strains from secondary hospitals and children's hospitals.Conclusions E.coli is an important pathogen causing clinical infection.More than half of the clinical isolates produced ESBL.The prevalence of CREco is increasing in secondary and tertiary hospitals over the 7-year period even though the overall prevalence is still low.This is an issue of concern.

The PA-PB1 interface of the influenza polymerase is an attractive site for antiviral drug design. In this study, we designed and synthesized a mini-library of indazole-containing compounds based on rational structure-based design to target the PB1-binding interface on PA. Biological evaluation of these compounds through a viral yield reduction assay revealed that compounds 27 and 31 both had a low micromolar range of the half maximal effective concentration (EC₅₀) values against A/WSN/33 (H1N1) (8.03 μmol/L for 27; 14.6 μmol/L for 31), while the most potent candidate 24 had an EC₅₀ value of 690 nM. Compound 24 was effective against different influenza strains including a pandemic H1N1 strain and an influenza B strain. Mechanistic studies confirmed that compound 24 bound PA with a K _d which equals to 1.88 μmol/L and disrupted the binding of PB1 to PA. The compound also decreased the lung viral titre in mice. In summary, we have identified a potent anti-influenza candidate with potency comparable to existing drugs and is effective against different viral strains. The therapeutic options for influenza infection have been limited by the occurrence of antiviral resistance, owing to the high mutation rate of viral proteins targeted by available drugs. To alleviate the public health burden of this issue, novel anti-influenza drugs are desired. In this study, we present our discovery of a novel class of indazole-containing compounds which exhibited favourable potency against both influenza A and B viruses. The EC₅₀ of the most potent compounds were within low micromolar to nanomolar concentrations. Furthermore, we show that the mouse lung viral titre decreased due to treatment with compound 24. Thus our findings identify promising candidates for further development of anti-influenza drugs suitable for clinical use.

OBJECTIVE: To investigate the associations between eight serum per- and polyfluoroalkyl substances (PFASs) and regional fat depots, we analyzed the data from the National Health and Nutrition Examination Survey (NHANES) 2011-2018 cycles. METHODS: Multiple linear regression models were developed to explore the associations between serum PFAS concentrations and six fat compositions along with a fat distribution score created by summing the concentrations of the six fat compositions. The associations between structurally grouped PFASs and fat distribution were assessed, and a prediction model was developed to estimate the ability of PFAS exposure to predict obesity risk. RESULTS: Among females aged 39-59 years, trunk fat mass was positively associated with perfluorooctane sulfonate (PFOS). Higher concentrations of PFOS, perfluorohexane sulfonate (PFHxS), perfluorodecanoate (PFDeA), perfluorononanoate (PFNA), and n-perfluorooctanoate (n-PFOA) were linked to greater visceral adipose tissue in this group. In men, exposure to total perfluoroalkane sulfonates (PFSAs) and long-chain PFSAs was associated with reductions in abdominal fat, while higher abdominal fat in women aged 39-59 years was associated with short-chain PFSAs. The prediction model demonstrated high accuracy, with an area under the curve (AUC) of 0.9925 for predicting obesity risk. CONCLUSION PFAS exposure is associated with regional fat distribution, with varying effects based on age, sex, and PFAS structure. The findings highlight the potential role of PFAS exposure in influencing fat depots and obesity risk, with significant implications for public health. The prediction model provides a highly accurate tool for assessing obesity risk related to PFAS exposure.
Humans ; Fluorocarbons/blood* ; Female ; Adult ; Middle Aged ; Male ; Environmental Pollutants/blood* ; Abdominal Fat ; Nutrition Surveys ; Alkanesulfonic Acids/blood* ; Obesity ; Environmental Exposure