BACKGROUND: The effect of air pollution on annual change rates in grip strength and body composition in the elderly is unknown. OBJECTIVES: This study evaluated the effects of long-term exposure to ambient air pollution on change rates of grip strength and body composition in the elderly. METHODS: In the period 2016-2020, grip strength and body composition were assessed and measured 1-2 times per year in 395 elderly participants living in the Taipei basin. Exposure to ambient fine particulate matters (PM_2.5), nitric dioxide (NO₂), and ozone (O₃) from 2015 to 2019 was estimated using a hybrid Kriging/Land-use regression model. In addition, long-term exposure to carbon monoxide (CO) was estimated using an ordinary Kriging approach. Associations between air pollution exposures and annual changes in health outcomes were analyzed using linear mixed-effects models. RESULTS: An inter-quartile range (4.1 µg/m³) increase in long-term exposure to PM_2.5 was associated with a faster decline rate in grip strength (-0.16 kg per year) and skeletal muscle mass (-0.14 kg per year), but an increase in body fat mass (0.21 kg per year). The effect of PM_2.5 remained robust after adjustment for NO₂, O₃ and CO exposure. In subgroup analysis, the PM_2.5-related decline rate in grip strength was greater in participants with older age (>70 years) or higher protein intake, whereas in skeletal muscle mass, the decline rate was more pronounced in participants having a lower frequency of moderate or strenuous exercise. The PM_2.5-related increase rate in body fat mass was higher in participants having a lower frequency of strenuous exercise or soybean intake. CONCLUSIONS Among the elderly, long-term exposure to ambient PM_2.5 is associated with a faster decline in grip strength and skeletal muscle mass, and an increase in body fat mass. Susceptibility to PM_2.5 may be influenced by age, physical activity, and dietary protein intake; however, these modifying effects vary across different health outcomes, and further research is needed to clarify their mechanisms and consistency.
Humans ; Hand Strength ; Aged ; Male ; Female ; Environmental Exposure/adverse effects* ; Follow-Up Studies ; Taiwan ; Air Pollution/adverse effects* ; Particulate Matter/adverse effects* ; Muscle, Skeletal/drug effects* ; Air Pollutants/adverse effects* ; Ozone/adverse effects* ; Aged, 80 and over ; Adipose Tissue/drug effects* ; Body Composition/drug effects* ; Nitrogen Dioxide/adverse effects*

Metformin has been demonstrated to attenuate hyperglycaemia by modulating the gut microbiota. However, the mechanisms through which the microbiome mediates metformin monotherapy failure (MMF) are unclear. Herein, in a prospective clinical cohort study of newly diagnosed type 2 diabetes mellitus (T2DM) patients treated with metformin monotherapy, metagenomic sequencing of faecal samples revealed that Phocaeicola vulgatus abundance was approximately 12 times higher in nonresponders than in responders. P. vulgatus rapidly hydrolysed taurine-conjugated bile acids, leading to ceramide accumulation and reversing the improvements in glucose intolerance conferred by metformin in high-fat diet-fed mice. Interestingly, C22:0 ceramide bound to mitochondrial fission factor to induce mitochondrial fragmentation and impair hepatic oxidative phosphorylation in P. vulgatus-colonized hyperglycaemic mice, which could be exacerbated by metformin. This work suggests that metformin may be unsuitable for P. vulgatus-rich T2DM patients and that clinicians should be aware of metformin toxicity to mitochondria. Suppressing P. vulgatus growth with cefaclor or improving mitochondrial function using adenosylcobalamin may represent simple, safe, effective therapeutic strategies for addressing MMF.

CD20 is a surface marker protein of B-cell lymphoma, and its extracellular region is the target of specific antibodies and drugs. To obtain a cheap and easily modified specific preparation targeting CD20, we optimized the gene of CD20 extracellular region according to codon degeneracy to facilitate its expression in Escherichia coli. The optimized gene was cloned into pGEX-4T-1 vector, and the recombinant vector was transformed into E. coli BL21(DE3) for expression. The purified protein was identified by SDS-PAGE and Western blotting. Systematic evolution of ligands by exponential enrichment (SELEX) was employed to screen the ssDNA aptamer that specifically binds to the fusion protein, and the affinity of the aptamer to CD20 was detected by flow cytometry. Then, the cytotoxicity test was carried out to examine the inhibitory effect of the aptamer on B lymphoma cells. In this study, we established the prokaryotic expression method of CD20 and obtained the aptamer specifically binding to the extracellular region of CD20, which laid a foundation for the development of therapeutic drugs targeting CD20.
Humans ; Escherichia coli/metabolism* ; SELEX Aptamer Technique/methods* ; Aptamers, Nucleotide/genetics* ; Antigens, CD20/metabolism* ; Ligands

Rapid epidemiological screening for tuberculosis (TB) usually uses tuberculin pure protein derivative (PPD) skin test, which has limitations such as low specificity and high side effects. ESAT-6 and CFP-10 are secreted proteins of Mycobacterium tuberculosis, but the related genes are missing from Bacillus Calmette-Guerin (BCG). In this study, the fusion protein ESAT6-CFP10 (EC) was expressed and purified, and prepared into chitosan nanoparticles (EC-NPs), which were loaded into the microneedle patch and carried out the preliminary test of tuberculosis skin test. The drug loading capacity of MNP-EC-NPs (microneedle patch, MNP) can reach 0.03 μg per needle and 1.92 μg per patch. The shelf life of MNP-EC-NPs can reach 6 months at room temperature, and it can effectively penetrate the epidermis. Volunteer skin test results showed that MNP-EC-NPs can effectively distinguish between BCG vaccinators, and can effectively show positive reaction in the skin of tuberculosis patients without significant side effects. The experiment was approved by the Ethics Committee of Wuhan Pulmonary Hospital [2022 (2)]. In this study, a TB skin test method was established, using ESAT6-CFP10 fusion protein instead of PPD, and using soluble microneedle dosage form, which improved the specificity of TB skin test diagnosis and provided a new technical scheme for TB epidemic screening.

The anti-inflammatory efficacy of Callicarpa nudiflora extract were evaluated upon lipopolysaccharide (LPS)-induced infective inflammation in rats. Pathological changes of lung and colon tissues observed with hematoxylin-eosin (H&E) staining, together with inflammatory factors in serum, including nitric oxide (NO), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), were applied to assess the mitigating effects of C. nudiflora water extract on model rats. The experimental protocol strictly adhered to the guidelines of the Ethics Committee of Animal Research of Guangdong Pharmaceutical University (Approval: gdpulac2022132). Quality markers with anti-inflammatory activities were recognized by network pharmacology analysis. Subsequently, a reliable method for simultaneously quantifying six components was established. As a result, the pathological injury on lung and colon tissues of model rats induced by LPS were improved by C. nudiflora water extract. Compared with model group, C. nudiflora extract had decreased the release of proinflammatory factors in serum, including TNF-α and IL-6, and reduced the NO (P < 0.01). Network pharmacological analysis obtained 83 chemical components, 466 component targets, 584 disease targets and 129 action targets, which were mainly concentrated in 624 biological processes such as inflammatory response and positive regulation of nitric oxide biosynthesis, as well as 162 pathways such as phosphatidylinositol-3-hydroxykinase-protein kinase (PI3K-Akt) signal pathway and Janus kinase-signal transducer and activator of transcription 3 (JAK-STAT3) signal pathway. Upon analyzing their specificity, effectiveness, detectability, and quantity transfer rule from herb to extract, 6-hydroxyluteolin 7-glucoside, cynaroside, caffeic acid, acteoside, isoacteoside, and forsythoaside B were identified as the quality markers. Their anti-inflammatory activities were verified with LPS-induced inflammation model of RAW264.7 cells. Then contents of these 6 quality markers in 16 batches of C. nudiflora were determined. Thereby, the anti-inflammatory efficacy of C. nudiflora extract were confirmed in vivo, 6-hydroxyluteolin 7-glucoside, cynaroside, caffeic acid, acteoside, isoacteoside, and forsythoaside B were identified as anti-inflammatory ingredients, which can be used as quality control indicators for the herb and related formulation.

Objective To study the effective fraction and mechanism of Lycium barbarum leaves on improving learning and memory ability of subacute aging mice induced by D-galactose injection.Methods The model of subacute aging mice was developed by injection of D-galactose subcutaneously,and different extracts of Lycium barbarum leaves were prepared.The effects of the extracts of Lycium barbarum leaves on the learning and memory ability of model mice were evaluated by Y maze experiment and new object recognition experiment.The pathomorphological changes of hippocampus in mice were observed by hematoxylin-eosin and Nissl staining.The levels of brain-derived neurotrophic factor(BDNF),nerve growth factor(NGF),glial cell line-derived neurotrophic factor(GDNF),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interferon-γ(IFN-γ)and interleukin-10(IL-10)in hippocampus of mice were detected by enzyme-linked immunosorbent assay.The activities of superoxide dismutase(SOD)and the contents of glutathione(GSH)and malondialdehyde(MDA)in hippocampus of mice were detected by related assay kits.Detection of apoptosis in the hippocampal region of mouse brain tissue using the TUNEL method.Western blotting analysis was used to detect the expressions of antioxidant proteins Nrf2,HO-1 and apoptotic proteins Caspase-3,Caspase-9 in hippocampus of mice.Results The water extraction part and 80%alcohol precipitation supernatant part of Lycium barbarum leaves significantly improved the learning and memory ability of model mice,improved the pathological damage of hippocampus in mice,increased the number of Nissl bodies in hippocampus of mice,and promoted the expression of neurotrophic factors BDNF,NGF and GDNF,and promoted the expression of neurotrophic factors BDNF,NGF and GDNF.Pro-inflammatory factors TNF-α,IL-1β and IFN-γ expression declines while anti-inflammatory factor IL-10 expression rises.The activity of SOD and the expression of GSH were increased,and the expression of MDA was decreased.Increase the expression of Nrf2 and HO-1 antioxidant proteins;reduce the expression of Caspase-3 and Caspase-9 apoptosis pathway proteins.Inhibition of apoptosis in the hippocampal region of mouse brain tissue using a model.Conclusion The water extracts and 80%alcohol precipitation supernatant extracts of Lycium barbarum leaves are the effective fractions of Lycium barbarum leaves to improve the learning and memory ability of D-galactose-induced subacute aging mice,and its mechanism might be related to the inhibition of neuronal apoptosis caused by oxidative stress and inflammation.

Objective To obtain the monitoring measurement range of quality indicators of red blood cells,plasma and derivatives and leukocyte-reduced apheresis platelets provided by blood stations in Hebei province,explore the distribution of monitoring values and the change of monitoring level,so as to further strengthen the homogenization construction of quality control laboratories in blood stations in Hebei.Methods In 2023,the sampling data of 12 blood stations in Hebei from 2015 to 2022 were collected,scatter plots were made and the range markers were set,and the"mean±SD"line was taken as the upper limit and lower limit of the measurement range.In 2024,the monitoring values in 2023 were added,and the changes of two measurement ranges were compared to analyze the stability and overall level.Results Comparison of the measurement range from 2015 to 2022 and the measurement range from 2015 to 2023 showed that the standard deviation of the content of deleukocyte suspension of red blood cells-hemoglobin,washed erythrocyte-hemoglobin,washed erythrocyte-su-pernatant protein,cryoprecipitate coagulation factor-FⅧ,fresh frozen plasma-FⅧ,leukocyte-reduced apheresis platelets-leukocyte residue and leukocyte-reduced apheresis platelet-red blood cell concentration decreased from 8.132 to 7.993,6.252 to 6.104,0.273 to 0.267,57.506 to 56.276,0.920 to 0.892,0.653 to 0.644 and 2.653 to 2.603,respectively.The narrowing of the standard deviation range of the above items led to more concentrated monitoring values and reduced disper-sion.Comparison of the measurement range from 2015 to 2022 and the measurement range from 2015 to 2023 showed that the mean value of leukocyte residue of the deleukocyte suspension of red blood cells,hemoglobin content of the wash eryth-rocyte,protein content of supernatant of the wash erythrocyte,hemolysis rate of the wash erythrocyte,FⅧ content of the cryoprecipitate coagulation factor,plasma protein content of the fresh frozen plasma,FⅧ content of the fresh frozen plasma,platelet content of the leukocyte-reduced apheresis platelets changed from 0.362 to 0.476,44.915 to 44.861,0.280 to 0.283,0.137 to 0.142,133.989 to 133.271,60.262 to 60.208,1.301 to 1.277 and 3.036 to 3.033,respectively,and was closer to the national standard line,which reflects an increase in the number of unqualified monitoring values or values close to the national standard line in 2023.The long-term qualified rate of coagulation items was low,and no improvement has been ob-served.The stability of biochemical items has been enhanced but overall deviation has occurred,with the average value close to the national standard line.The possibility of subsequent testing failure has increased.The counting items showed no obvi-ous common characteristics.Conclusion The use of"mean±SD"in the analysis can visually display the distribution of mo-nitoring values of different items in Hebei,forming an indicator measurement range covering the past nine years.It shows the characteristics of each item,and provides reference for subsequent quality control laboratory data analysis of each blood sta-tions to takes active measures to improve the monitoring level.

OBJECTIVE To evaluate the effect of Qishen Yizhi formula on improving learning and memory ability in D-galactose subcutaneous injection induced subacute aging mice.METHODS Subacute aging mice model mice were developed by D-galactose subcutaneous injection and then treated with positive drug donepezil(2 mg·kg-1·d-1)and Qishen Yizhi formula water extracts in low(1.33 g·kg-1·d-1)and high dose group(2.67 g·kg-1·d-1).The learning and memory abilities of mice were evaluated using Morris water maze and Y maze tests;HE staining was used to examine hippocampal damage in model mice;TUNEL was used to detect apoptosis of mouse hippocampal tissue;ELISA was used to detect the expression levels of oxidative stress factors and inflammatory fac-tors in the mouse hippocampus tissue;Western blot was used to detect the expression of signaling pathway proteins related to apoptosis,oxidative stress and inflammatory stress in the hippocampus of mice.RESULTS The water extract of Qishen Yizhi formula signifi-cantly shortened the latency and distance of model mice for reaching the platform in the water maze test(P<0.01),and significantly increased the number of crossing the platform(P<0.01);increased the exploration time and number of the Y maze new arm in model mice(P<0.05);inhibited the TUNEL fluorescence expression in the hippocampus of model mice(P<0.01);upregulated the activity of the oxidative stress factor superoxide dismutase(SOD)(P<0.05)and glutathione(GSH)content(P<0.05),and downregulated malondialdehyde(MDA)content(P<0.05);reduced interleukin(IL)-1β,IL-6 and tumor necrosis factor(TNF-α)expression levels(P<0.05,P<0.01);decreased the expression of apoptosis signaling pathway proteins Cleaved Caspase-3 and Caspase-3(P<0.05),upregulated the expression of oxidative stress signaling pathway proteins Nrf2 and HO-1(P<0.05),and downregulated the expression of inflammatory stress signaling pathway proteins p-NF-κB and NF-κB(P<0.05).CONCLUSION Qishen Yizhi for-mula can improve the learning and memory ability of subacute aging model mice injected with D-galactose,which may be related to its inhibitory effect on hippocampal oxidative stress and inflammatory stress.

Objective To investigate the distribution and antimicrobial resistance profiles of the common pathogens isolated from urine from 2015 to 2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods The bacterial strains were isolated from urine and identified routinely in 51 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Antimicrobial susceptibility was determined by Kirby-Bauer method,automatic microbiological analysis system and E-test according to the unified protocol.Results A total of 261 893 nonduplicate strains were isolated from urine specimen from 2015 to 2021,of which gram-positive bacteria accounted for 23.8％(62 219/261 893),and gram-negative bacteria 76.2％(199 674/261 893).The most common species were E.coli(46.7％),E.faecium(10.4％),K.pneumoniae(9.8％),E.faecalis(8.7％),P.mirabilis(3.5％),P.aeruginosa(3.4％),SS.agalactiae(2.6％),and E.cloacae(2.1％).The strains were more frequently isolated from inpatients versus outpatients and emergency patients,from females versus males,and from adults versus children.The prevalence of ESBLs-producing strains in E.coli,K.pneumoniae and P.mirabilis was 53.2％,52.8％and 37.0％,respectively.The prevalence of carbapenem-resistant strains in E.coli,K.pneumoniae,P.aeruginosa and A.baumannii was 1.7％,18.5％,16.4％,and 40.3％,respectively.Lower than 10％of the E.faecalis isolates were resistant to ampicillin,nitrofurantoin,linezolid,vancomycin,teicoplanin and fosfomycin.More than 90％of the E.faecium isolates were ressitant to ampicillin,levofloxacin and erythromycin.The percentage of strains resistant to vancomycin,linezolid or teicoplanin was＜2％.The E.coli,K.pneumoniae,P.aeruginosa and A.baumannii strains isolated from ICU inpatients showed significantly higher resistance rates than the corresponding strains isolated from outpatients and non-ICU inpatients.Conclusions E.coli,Enterococcus and K.pneumoniae are the most common pathogens in urinary tract infection.The bacterial species and antimicrobial resistance of urinary isolates vary with different populations.More attention should be paid to antimicrobial resistance surveillance and reduce the irrational use of antimicrobial agents.

Objective To understand the distribution and changing resistance profiles of clinical isolates of Enterococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Enterococcus according to the unified protocol of CHINET program by automated systems,Kirby-Bauer method,or E-test strip.The results were interpreted according to the Clinical & Laboratory Standards Institute(CLSI)breakpoints in 2021.WHONET 5.6 software was used for statistical analysis.Results A total of 124 565 strains of Enterococcus were isolated during the 7-year period,mainly including Enterococcus faecalis(50.7％)and Enterococcus faecalis(41.5％).The strains were mainly isolated from urinary tract specimens(46.9％±2.6％),and primarily from the patients in the department of internal medicine,surgery and ICU.E.faecium and E.faecalis strains showed low level resistance rate to vancomycin,teicoplanin and linezolid(≤3.6％).The prevalence of vancomycin-resistant E.faecalis and E.faecium was 0.1％and 1.3％,respectively.The prevalence of linezolid-resistant E.faecalis increased from 0.7％in 2015 to 3.4％in 2021,while the prevalence of linezolid-resistant E.faecium was 0.3％.Conclusions The clinical isolates of Enterococcus were still highly susceptible to vancomycin,teicoplanin,and linezolid,evidenced by a low resistance rate.However,the prevalence of linezolid-resistant E.faecalis was increasing during the 7-year period.It is necessary to strengthen antimicrobial resistance surveillance to effectively identify the emergence of antibiotic-resistant bacteria and curb the spread of resistant pathogens.