Copper is an essential trace element in the human body, extensively involved in key physiological and biochemical processes such as antioxidant defense, energy metabolism, neural signaling, and immune regulation. In recent years, increasing research has focused on the potential role of copper dyshomeostasis in the development of chronic diseases. Studies indicate that abnormal copper levels, particularly elevated free copper, may increase the risk of cardiovascular disease, neurodegenerative disorders, diabetes, and cancer by inducing oxidative stress, impairing mitochondrial function, and disrupting immune regulation. Concurrently, copper homeostasis abnormalities have been demonstrated to be closely associated with increased all-cause mortality and accelerated aging. This systematic review comprehensively examined physiological functions, metabolic pathways, and environmental exposure characteristics of copper. It emphasized the epidemiological and mechanistic links between copper metabolism disorders and multiple chronic diseases, while exploring the potential applications of copper ion transporters and chelating agents in disease intervention. This work provides scientific evidence for the prevention, control, and precision treatment of copper-related chronic diseases.

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 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.

Enteric human adenovirus(HAdV),a common cause of acute viral gastroenteritis in children,frequently triggers spo-radic infections,nosocomial transmissions,and outbreaks in kindergarten settings.This study was aimed at investigating the molecular characteristics and genetic evolution of enteric HAdV among patients with acute gastroenteritis younger than 5 years in China,to pro-vide foundational data for disease prevention and control.A total of 8 074 stool samples were collected from hospitalized or outpatient children younger than 5 years with acute gastroenteritis in China during 2023.HAdV screening was conducted with real-time fluores-cence PCR.Positive samples were sequenced,then subjected to bioinformatics analysis including genotyping,homology assessment,and phylogenetic analysis with GenBank,BioAider,and MEGA11.0.A total of 370 samples(4.58%)tested positive for HAdV.Two enteric HAdV genotypes were identified:HAdV-F41(which predominated,at 98.09%)and HAdV-F40(1.90%).HAdV-F41 was the dominant genotype among patients with acute gastroenteritis younger than 5 years in China.Bioinformatics analysis indicated that the predominant HAdV lineages in China were lineage 1 and 2,whereas European lineage 3 showed no influence.Systematic and long-term surveillance of HAdV should help elucidate its diversity and evolutionary patterns in China,thereby providing scientific evi-dence for developing more effective prevention strategies.

Enteric human adenovirus(HAdV),a common cause of acute viral gastroenteritis in children,frequently triggers spo-radic infections,nosocomial transmissions,and outbreaks in kindergarten settings.This study was aimed at investigating the molecular characteristics and genetic evolution of enteric HAdV among patients with acute gastroenteritis younger than 5 years in China,to pro-vide foundational data for disease prevention and control.A total of 8 074 stool samples were collected from hospitalized or outpatient children younger than 5 years with acute gastroenteritis in China during 2023.HAdV screening was conducted with real-time fluores-cence PCR.Positive samples were sequenced,then subjected to bioinformatics analysis including genotyping,homology assessment,and phylogenetic analysis with GenBank,BioAider,and MEGA11.0.A total of 370 samples(4.58%)tested positive for HAdV.Two enteric HAdV genotypes were identified:HAdV-F41(which predominated,at 98.09%)and HAdV-F40(1.90%).HAdV-F41 was the dominant genotype among patients with acute gastroenteritis younger than 5 years in China.Bioinformatics analysis indicated that the predominant HAdV lineages in China were lineage 1 and 2,whereas European lineage 3 showed no influence.Systematic and long-term surveillance of HAdV should help elucidate its diversity and evolutionary patterns in China,thereby providing scientific evi-dence for developing more effective prevention strategies.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

AIM: To investigate the diagnostic value of the difference of binocular biological parameters of the anterior segment in early keratoconus.METHODS: Retrospective case-control study. A total of 183 patients(366 eyes)who visited our hospital from March 2022 to November 2023 were included, including 107 cases(214 eyes)in the control group(patients with simple refractive error), 40 cases(80 eyes)in the subclinical keratoconus group, and 36 cases(72 eyes)in the clinical keratoconus group. All of the patients were examined by the Pentacam anterior segment analyzer to determine the inferior-superior 3 mm of the posterior corneal surface(I-S), corneal posterior elevation of the thinnest point(P.E.), maximum posterior elevation of the best fit sphere(MPE from BFS), the maximum posterior elevation of the best fit toric ellipsoid(MPE from BFTE), posterior aspherical asymmetry index(AAI), central corneal thickness(CCT), thinnest corneal thickness(TCT), pachymetric progression index average(PPIavg), Ambrósio relational thickness maximum(ARTmax), Belin/ Ambrósio enhanced ectasia display(BAD-D), and the binocular difference of each test was calculated separately for each patient. The control group was further divided according to corneal diameter: 21 cases(42 eyes)with corneal diameter <11.2 mm in group A, 54 cases(108 eyes)with 11.2 mm≤ corneal diameter ≤11.8 mm in group B, and 32 cases(64 eyes)with corneal diameter >11.8 mm in group C.RESULTS: There was significant differences in the binocular I-S, P.E., MPE from BFS, MPE from BFTE, AAI, CCT, TCT, PPIavg, ARTmax and BAD-D between the clinical keratoconus group and the control group(P<0.05). The difference of binocular I-S, P.E., MPE from BFS, MPE from BFTE, AAI, CCT, TCT, PPIavg, and BAD-D were of high diagnostic value(AUC≥0.900), with the best diagnostic ability for P.E. and BAD-D, and an AUC as high as 0.999 and 0.995, respectively. The difference of binocular P.E. and ARTmax between the subclinical keratoconus group and the control group were statistically significant(P<0.05). The difference of binocular I-S, P.E. and BAD-D had high diagnostic value for subclinical keratoconus(AUC≥0.900). In the control group A, B and C, there were no significant difference in binocular I-S, CCT, TCT, MPE from BFS, MPE from BFTE, AAI, PPIavg and ARTmax(all P>0.05), and none of them had correlation with corneal diameter(P>0.05); however, there were statistical significant differences in binocular P.E. and BAD-D in the control group A, B and C(P=0.007, 0.003), while the P.E. differences had no correlation with corneal diameter(P=0.270), and binocular BAD-D differences were negatively correlated with corneal diameter(r=-0.230, P=0.017).CONCLUSION: Pentacam anterior segment analyzer can accurately measure a variety of corneal biological parameters. Difference of binocular corneal I-S, P.E. and BAD-D are sensitive indexes for the early diagnosis of keratoconus. Among them, difference of binocular I-S and P.E. are less affected by corneal diameter, thus being significant for the early diagnosis of keratoconus with different cornea diameters.

Objective To investigate the relationship between serum histone deacetylase 4(HDAC4)and myeloid differentiation protein 88(MYD88)levels and hemorrhagic transformation after intravenous throm-bolysis with recombinant tissue plasminogen activator(rt-PA)in patients with acute cerebral infarction(ACI).Methods A total of 169 patients with ACI who were treated with rt-PA intravenous thrombolysis in this hospital from May 2020 to May 2022 were selected as the research objects,and they were divided into transformation group(46 cases)and non-transformation group(123 cases)according to whether hemorrhagic transformation occurred after rt-PA intravenous thrombolysis.In addition,156 healthy people who underwent physical examination in the hospital during the same period were selected as the control group.Enzyme-linked immunosorbent assay was used to detect the serum levels of HDAC4 and MYD88 in each group,and the gen-eral data of transformation group and non-transformation group were compared.Pearson correlation was used to analyze the correlation between serum HDAC4 and MYD88 levels in ACI patients.Multivariate Logistic re-gression analysis was used to analyze the related factors of hemorrhagic transformation in ACI patients after intravenous thrombolysis with rt-PA.The receiver operating characteristic(ROC)curve was used to evaluate the diagnostic value of HDAC4,MYD88 levels and their combination for hemorrhagic transformation in ACI patients after rt-PA intravenous thrombolysis.Results The serum level of HDAC4 in ACI group was signifi-cantly lower than that in control group,and the serum level of MYD88 in ACI group was significantly higher than that in control group(P＜0.05).There were no significant differences in gender,age,body mass index,fasting blood glucose,hyperlipidemia,and coronary heart disease between the non-transformation group and the transformation group(P＞0.05),while there were significant differences in atrial fibrillation,National In-stitute of Health Stroke Scale(NIHSS)score,and the time from onset to thrombolysis between the two groups(P＜0.05).The level of serum HDAC4 in transformation group was lower than that in non-transfor-mation group,and the level of serum MYD88 in transformation group was higher than that in non-transforma-tion group,and the difference was statistically significant(P＜0.05).Pearson correlation analysis showed that serum HDAC4 level was negatively correlated with MYD88 in ACI patients(r=-0.401,P＜0.001).Multi-variate Logistic regression analysis showed that atrial fibrillation,time from onset to thrombolysis,NIHSS score and MYD88 level were the risk factors for hemorrhagic transformation in ACI patients after rt-PA intra-venous thrombolysis,HDAC4 level was a protective factor for hemorrhagic transformation in ACI patients af-ter intravenous thrombolysis with rt-PA(P＜0.05).The area under the curve(AUC)of combined HDAC4 and MYD88 was 0.876,and the sensitivity and specificity were 65.22％and 98.37％,respectively,which was better than that of HDAC4 and MYD88 alone(Zcombined-HDAC4=2.298,P=0.022;Zcombined-MYD88=2.5 4 5,P=0.011).Conclusion The serum levels of HDAC4 and MYD88 in ACI patients are closely related to hemor-rhagic transformation after intravenous thrombolysis with rt-PA.

Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.

Objective:To determine incidence of seasonal influenza virus infection in the community and to analyze the factors influencing seasonal influenza virus infection.Methods:This study recruited residents aged 6-59 years to build a cohort in 15 villages/streets in Macheng city in November 2019. Meanwhile, a cross-sectional baseline survey was conducted immediately to collect sera, information on demographics and child protection knowledge, behaviors, as well as attitudes using a questionnaire from the participants enrolled in the cohort (i.e., before the influenza epidemic season). In July 2020, a cross-sectional follow-up survey was conducted to collect sera once again (i.e., after the influenza season). Paired sera from the two cross-sectional surveys were tested for influenza virus-specific antibodies by hemagglutination inhibition (HI) test or micro-neutralization (MN) test using a circulating representative strain of each subtype/lineage of influenza virus as the test antigen. The infections with influenza virus subtype/lineage was confirmed if there was a four-fold or more increase in titers of antibodies against circulating representative strain of the subtype/lineage of influenza virus. Factors influencing infection with influenza A (H3N2) and B/Victoria viruses were analyzed using univariable and multivariable logistic regression.Results:In November 2019, 800 study participants were enrolled in the cohort, including 340 children aged 6-17 years and 460 adults aged 18-59 years; 605 study participants (including 224 children and 381 adults) were followed up in July 2020 and their paired sera were obtained before and after the influenza season. 25.3% (153/605) of the participants were confirmed to be infected with at least one subtype/lineage of seasonal influenza virus by HI and MN tests. The overall incidence of influenza viruses of all subtypes/lineages in children was 44.2% (95% CI: 37.6%-50.8%) which was significantly higher than the incidence of 14.1% in adults (95% CI: 10.7%-17.7%). Children had the highest incidence of influenza A (H3N2) virus infection, followed by B/Victoria. MN or HI antibody titers in A (H3N2)[ OR=0.88 (95% CI: 0.84-0.93)] and B/Victoria[ OR=0.97 (95% CI: 0.95-0.99)] before the influenza season were significantly associated with whether children were infected with that subtype/lineage of influenza virus. Conclusions:The residents aged 6-59 years in Macheng city had a substantial incidence of seasonal influenza virus infection during the influenza season from winter 2019 to spring 2020. Notably, almost half of children aged 6-17 years have been infected with seasonal influenza virus. Higher titers of HI/MN antibodies against seasonal influenza virus before the influenza season would be likely to reduce the risk of infection with influenza A (H3N2) and B/Victoria.