Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

ObjectiveTo analyze the incidence rate and mortality of acute myocardial infarction (AMI) and their changing trends among the registered residents in Xiaoshan District, Hangzhou City from 2017 to 2023, so as to provide references for formulating policies related to AMI prevention. MethodsThe morbidity and mortality data of AMI among the registered residents in Xiaoshan District from 2017 to 2023 were collected through the Hangzhou Chronic Disease and Death Cause Monitoring System. Software such as Excel 2019, SPSS 25.0 and Joinpoint 4.9.1.0 were used to calculate the incidence rate, mortality, and average annual percentage change (AAPC) of AMI. ResultsFrom 2017 to 2023, the average annual crude incidence rate, age-standardized incidence rate using China standard population (ASIRC), and the age-standardized incidence rate using World standard population (ASIRW) of AMI in Xiaoshan District were 48.25/100 000, 29.14/100 000, and 21.64/100 000, respectively, and, from which the AAPCs were 5.495%, 6.010%, and 6.533%, respectively, all showing an upward trend. The average annual crude mortality rate, the age-standardized mortality rate using China standard population (ASMRC), and the age-standardized mortality rate using World standard population (ASMRW) were 11.76/100 000, 6.52/100 000, and 4.71/100 000, respectively, from which the AAPCs were -9.669%, -10.433% and -9.615%, respectively, all showing a downward trend. The average annual crude incidence rate of AMI was higher in males (65.87/100 000) than that in females (31.31/100 000). Moreover, the average annual crude mortality rate of AMI was higher in males (14.08/100 000) than that in females (9.52/100 000), and the difference was statistically significant (all P<0.001) .After age grouping, the crude incidence rate of AMI among the residents aged 35-, 45-, 55-, and 65- years in Xiaoshan District from 2017 to 2023 showed an upward trend over time, with AAPCs of 16.993%, 17.149%, 8.523%, and 5.002%, respectively. While the crude mortality rate in residents aged 35-, 75-, and 85-102 years showed an decreasing trend over time, with AAPCs of -23.977%, -15.467%, and -17.415%, respectively, but there was no statistically significant difference in the trends in incidence rate and mortality of other age groups (all P>0.05). ConclusionThe situation of AMI prevention and control among the registered residents in Xiaoshan District is not optimistic, and targeted measures should be strengthened for the male residents aged ≥35 years old.

Objective: To analyze the impact of maternal metal exposure during early pregnancy on the physical development of offspring at 1 and 3 years of age, so as to provide scientific evidence for reducing the adverse effects of heavy metals on their health. Methods: From 2024 to 2018, a total of 1 588 mother child pairs from the Jiangsu Birth Cohort (JBC) were included in this study. Multiple linear regression models, generalized estimating equations (GEE), and weighted quantile sum (WQS) regression models were used to assess the associations between 24 urinary metal mass concentrations (adjusted for specific gravity, SG) during early pregnancy and offspring growth outcomes, including length/height for age Z score(HAZ), weight for age Z score(WAZ), weight for length/height Z score(WHZ), and head circumference for age Z score(HCAZ) at 1 and 3 years of age. Results: After adjusting for confounders, GEE analysis revealed that each natural log unit increase in maternal urinary concentrations of vanadium, tin, cerium, lead, and uranium during early pregnancy was associated with an average reduction in HCAZ by 14.29%, 4.82%, 2.62 %, 5.04 %, and 8.33%, respectively, at 1 and 3 years of age (FDR- P <0.05). Multiple linear regression analysis revealed that increased urinary vanadium concentration was associated with reduced HAZ at 1 year of age, while increased urinary concentrations of vanadium, chromium, tin, antimony, and uranium were associated with reduced HCAZ at 1 year of age (FDR- P <0.05). In the WQS regression model, each unit increase in the WQS index was associated with a 22.64% reduction in HCAZ at 1 year of age, with tin (22.2%) contributing the highest weight, followed by uranium (16.2%), lead (11.5%), vanadium (10.0%), arsenic (6.5%), and chromium (5.0%). Conclusions Prenatal exposure to specific metals and their mixtures may significantly impact the physical development of offspring at 1 and 3 years of age, particularly head circumference. These findings highlight the need to enhance monitoring of maternal metal exposure during early pregnancy to reduce the potential health risks posed by environmental metal pollution to infants and young children.

Objective: To analyze the incidence trend of colorectal cancer in Xiaoshan District, Hangzhou City from 2010 to 2024, and predict the incidence of colorectal cancer from 2025 to 2027, so as to provide the evidence for improving the prevention and control strategies of colorectal cancer. Methods: Colorectal cancer incidence data from 2010 to 2024 in Xiaoshan District were collected through the Hangzhou Municipal Chronic Disease Monitoring Management System. The crude incidence of colorectal cancer was calculated, and standardized using the data from the Sixth National Population Census in 2010 (Chinese standardized rate) and the Segi's world standard population (world standardized rate). The trend of colorectal cancer incidence from 2010 to 2024 was analyzed using the average annual percent change (AAPC). An exponential smoothing state space model with trigonometric seasonality, box-cox transformation, ARMA errors, trend and seasonal components (TBATS) was established to forecast the crude incidence of colorectal cancer from 2025 to 2027. Results: There were 10 726 new cases of colorectal cancer in Xiaoshan District from 2010 to 2024. The crude incidence, Chinese standardized rate, and world standardized rate of colorectal cancer were 59.25/100 000, 38.62/100 000 and 29.50/100 000, respectively. The crude incidence, Chinese standardized rate, and world standardized rate of colorectal cancer in males were 70.56/100 000, 44.44/100 000and 35.58/100 000, respectively, while those in females were 48.37/100 000, 32.69/100 000 and 23.70/100 000, respectively. The Chinese standardized rate of colorectal cancer was significantly higher in males than in females (P<0.05). The crude incidence of colorectal cancer in males, females and the whole population showed upward trends from 2010 to 2024 (AAPC=4.916%, 3.795% and 4.442%, all P<0.05). The crude incidence of colorectal cancer in the groups of 0-<35, 35-<50, 50-<75 and ≥75 years were 1.75/100 000, 19.86/100 000, 112.28/100 000 and 272.99/100 000, respectively, showing an increasing trend with age (P<0.05). From 2010 to 2024, the crude incidence of colorectal cancer in the ≥75 years group showed an increasing trend (AAPC=4.470%, P<0.05), while no significant trend was observed in other age groups (all P>0.05). TBATS model demonstrated good fitting (predictive) performance, indicating a year-by-year increase in the crude incidence of colorectal cancer across the whole population from 2025 to 2027, with an estimated rate reaching 70.45/100 000 in 2027. Conclusions The crude incidence of colorectal cancer in Xiaoshan District showed an increasing trend from 2010 to 2024, and it is predicted to continue to increase from 2025 to 2027. Males and the elderly are the key populations for colorectal cancer prevention and control.

Background::While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.Methods::We evaluated phenotypic associations using data from the United Kingdom Biobank ( N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: Ncase/ Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DM adjBMI]: Ncase/ Ncontrol = 50,409/523,897) and for CAD ( Ncase/ Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM ( Ncase/ Ncontrol = 180,834/1,159,055). Results::Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01–2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63–1.81). A positive overall genetic correlation between T2DM and CAD was observed ( rg = 0.39, P = 1.43 × 10 -75), which was largely independent of BMI (T2DM adjBMI–CAD: rg = 0.31, P = 1.20 × 10 –36). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11-1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10-1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9-83.4%) and 90.4% (95% CI: 29.3-151.5%), respectively. Conclusion::Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.

Aim To investigate the protective effect of carnosine on BV2 cell damage induced by oxygen-glu-cose deprivation/reperfusion(OGD/R)and its role in mediating pyrodeath through the ROS/NLRP3/GSDMD pathway.Methods BV2 cells were randomly divided into the control group(Con),model group(OGD/R),carnosine group(OGD/R+CAR),inhibitor group(OGD/R+MCC950),and carnosine+inhibitor group(OGD/R+CAR+MCC950).The cell survival rate was detected by MTT assay.The release rate of lactate dehydrogenase(LDH)in cell supernatant was detected by microenzyme labeling method.Cell damage was as-sessed using Hoechst 33342/SYTOX Green staining.ROS levels in cells were detected by DCFH-DA.The nucleation level of NF-κB p65 was observed by immu-nofluorescence.The protein expression levels of NLRP3,ASC,cleaved caspase-1,and GSDMD-N were detected by Western blot.The levels of IL-1 β and IL-18 in the supernatant were detected by ELISA.Results Com-pared with Con group,the survival rate of cells in the OGD/R group was significantly reduced,LDH release was significantly raised,cell morphology was damaged,and the positive rate of SYTOX Green was significantly elevated with ROS level in cells.The fluorescence in-tensity of NF-κB p65 in the nucleus increased,and the protein expression levels of NLRP3,ASC,cleaved caspase-1,GSDMD-N increased significantly,and the levels of IL-1 β and IL-18 in the cell superserum in-creased significantly.Compared with the OGD/R group,the survival rate of cells in other groups in-creased significantly,the LDH release rate significantly decreased,and the cell damage was improved to a cer-tain extent.The positive rate of SYTOX Green and ROS production in cells significantly decreased,and the fluorescence intensity of NF-κB p65 in nucleus markedly decreased.The expression levels of related proteins and the levels of IL-1 β and IL-18 in cell super-natant significantly decreased.Conclusion Carnosine can protect BV2 cells from OGD/R-induced damage by inhibiting oxidative stress and NF-κB activation,then inhibiting NLRP3/GSDMD signaling pathway.

Aim To construct a DC-targeted modified(lacto-N-fucop-entose Ⅲ,LewisX)Pseudomonas aeruginosa(PA)DNA vaccine PLGA nanoparticle(LewisX-PLGA)loading PA PcrV and OprF genes combination,and provide a new idea for the prevention of PA clinical infection.Methods The PLGA nano-particles loading PA PcrV and OprF combined DNA(PLGA+PcrV/OprF)or loading pEGFP(PLGA+pEGFP)were pre-pared by double emulsification-solvent evaporation method.On this basis,the DC-SIGN-targeted ligand LewisX was connected to the surface of PLGA nanoparticles by amide condensation reac-tion.LewisX-modified PLGA-PcrV/OprF(LewisX-PLGA+PcrV/OprF)and LewisX-modified PLGA-pEGFP(LewisX-PL-GA+pEGFP)were prepared.Particle size,Zeta potential,en-capsulation rate and drug loading were evaluated to characterize LewisX-PLGA+PcrV/OprF.The cytotoxicity of LewisX-PLGA+PcrV/OprF was investigated by CCK-8.DC targeting of LewisX-PLGA+pEGFP was validated in vitro transfection.Further,LewisX-PLGA+PcrV/OprF lysosome escape was used to evalu-ate the targeting performance of LewisX-modified PLGA nanopar-ticles loading DNA in vitro.The immunoefficacy of the nanopar-ticles was evaluated by detecting the level of lymphocyte prolifer-ation,humoral immunity and immune protection.Results The diameter of LewisX-PLGA+PcrV/OprF was(201.17±1.6)nm.The encapsulation efficiency of LewisX-PLGA+PcrV/OprF was(85.72±5.3)％.The Zeta potential of LewisX-PLGA+PcrV/OprF was+(31.17±1.8)mV.In the DC2.4 cytotoxici-ty test,the cell survival rates were above 85％.The results of fluorescence microscopy after LewisX-PLGA+pEGFP transfec-tion in vitro showed that LewisX-PLGA+pEGFP was more readi-ly taken up by DC2.4,and LewisX-PLGA+pEGFP had a DC-SIGN specific targeting performance.The CLSM's observation of LewisX-PLGA+Pcrv/OprF showed that more DNA escaped from the lysosome into the cytoplasm.The results suggested that LewisX-PLGA had DC2.4 targeting performance.Because DC2.4 cells endocyted more LewisX-PLGA+Pcrv/OprF into the lysosome,the amount of DNA carried by the nanoparticles esca-ping into the cytoplasm increased.in vivo immune results showed that the lymphocyte proliferation level and antibody titer level of targeted DNA vaccine increased significantly,further improved the survival rate of mice infected with acute pneumoni-a,and reduced the bacterial load of mouse lungs.Conclusions The DC-SIGN-targeted aptamer-modified PA DNA vaccine nanoparticle LewisX-PLGA can be successfully constructed.It promotes the transfection of DNA into DC.It promotes the endo-cytosis of PA DNA vaccine into the DC lysosome and the escape of PA DNA into the cytoplasm.This results in a significant im-mune response in body,which enhances the protective efficacy of vaccine.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective To investigate the changing distribution and antibiotic resistance profiles of clinical isolates of Staphylococcus in hospitals across China from 2015 to 2021.Methods Antimicrobial susceptibility testing was conducted for the clinical isolates of Staphylococcus according to the unified protocol of CHINET(China Antimicrobial Surveillance Network)using disk diffusion method and commercial automated systems.The CHINET antimicrobial resistance surveillance data from 2015 to 2021 were interpreted according to the 2021 CLSI breakpoints and analyzed using WHONET 5.6.Results During the period from 2015 to 2021,a total of 204,771 nonduplicate strains of Staphylococcus were isolated,including 136,731(66.8％)strains of Staphylococcus aureus and 68,040(33.2％)strains of coagulase-negative Staphylococcus(CNS).The proportions of S.aureus isolates and CNS isolates did not show significant change.S.aureus strains were mainly isolated from respiratory specimens(38.9±5.1)％,wound,pus and secretions(33.6±4.2)％,and blood(11.9±1.5)％.The CNS strains were predominantly isolated from blood(73.6±4.2)％,cerebrospinal fluid(12.1±2.5)％,and pleural effusion and ascites(8.4±2.1)％.S.aureus strains were mainly isolated from the patients in ICU(17.0±7.3)％,outpatient and emergency(11.6±1.7)％,and department of surgery(11.2±0.9)％,whereas CNS strains were primarily isolated from the patients in ICU(32.2±9.7)％,outpatient and emergency(12.8±4.7)％,and department of internal medicine(11.2±1.9)％.The prevalence of methicillin-resistant strains was 32.9％in S.aureus(MRSA)and 74.1％in CNS(MRCNS).Over the 7-year period,the prevalence of MRSA decreased from 42.1％to 29.2％,and the prevalence of MRCNS decreased from 82.1％to 68.2％.MRSA showed higher resistance rates to all the antimicrobial agents tested except trimethoprim-sulfamethoxazole than methicillin-susceptible S.aureus(MSSA).Over the 7-year period,MRSA strains showed decreasing resistance rates to gentamicin,rifampicin,and levofloxacin,MRCNS showed decreasing resistance rates to gentamicin,erythromycin,rifampicin,and trimethoprim-sulfamethoxazole,but increasing resistance rate to levofloxacin.No vancomycin-resistant strains were detected.The prevalence of linezolid-resistant MRCNS increased from 0.2％to 2.3％over the 7-year period.Conclusions Staphylococcus remains the major pathogen among gram-positive bacteria.MRSA and MRCNS were still the principal antibiotic-resistant gram-positive bacteria.No S.aureus isolates were found resistant to vancomycin or linezolid,but linezolid-resistant strains have been detected in MRCNS isolates,which is an issue of concern.

Objective:To investigate the effects of mild SARS-CoV-2 infection on hematological parameters of adult blood donors and the suitability of apheresis platelet donation,the changes of the hematological parameters in blood donors with mild infection of the SARS-CoV-2 Omicron variant strain were evaluated.Methods:Seventy-two blood donors with mild COVID-19 symptoms who donated consecutive apheresis platelets for 3 times from December 2022 to January 2023,42 cases among which were included in the infection-positive group,and 30 cases in the suspected infection group.Forty-two donors un-vaccinated against SARS-CoV-2,un-infected,and donated three consecutive apheresis platelets from October to November 2022 were included in the control group.The changes of blood routine testing in the positive group and the suspected infection group were retrospectively compared before(Time1)and after(Time2 and Time3)the onset of symptoms,three consecutive times(Time1,Time2,Time3)in the control group by repeated measures analysis of variance.The Bayesian discriminant method was used to establish a discriminant equation to determine whether the recent infection of SARS-CoV-2 occurred or not.Results:Simple effect of the number times of tests in the positive and suspected infection groups was significant(Finfection-positive group=6.98,P＜0.001,partial η2=0.79,Fsuspected infection group=4.31,P＜0.001,partial η2=0.70).The positive group and the suspected infection group had lower RBC,HCT,and HGB,and higher PLT and PCT at Time2 compared to Time1 and Time3(P＜0.05).The positive group and the suspected infection group showes RDW-CV and RDW-SD at Time3 higher than Time1 and Time2(P＜0.001).The simple effect of the number times of tests in the control group was not significant(F=0.96,P=0.55,partial η2=0.34).The difference of the whole blood count parameters in the control group for three times was not statistically significant(P＞0.05).We established a discriminant equation to determine whether the recent infection of SARS-CoV-2 occurred or not.The equation had an eigenvalue of 0.22,a canonical correlation of 0.43(x2=27.81,P＜0.001),and an analysis accuracy of 72.9％.Conclusion:The hematological indicators of RBC,HCT,HGB,PLT,PCT,RDW-CV and RDW-SD in blood donors who had infected with mild COVID-19 showed dynamic changes.The discriminant equation for whether they are infected recently with COVID-19 has a high accuracy rate.