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.

Objective To investigate disparities in health levels among populations across different regions of China and analyze the relationship between these disparities and regional, social, and economic factors, and to provide recommendations to promote health equity. Methods Based on the data from the Seventh National Population Census, this study employed spatial autocorrelation analysis and the spatial Durbin model to conduct spatial and temporal analyses of the health status of the national population from 2012 to 2021, focusing on the regional distribution of health levels and related influencing factors. Results 1. Regional disparities: The mortality rate in Gansu Province rose from 6.05‰ in 2012 to 8.26‰ in 2021, whereas the mortality rate in eastern provinces such as Hainan Province was relatively low in 2021 (5.39‰). 2. Spatial clustering: The spatial correlation of mortality rates was weak (Moran's I: 0.134-0.245), and the high mortality clusters showed a shift from southwest to northeast region. 3. Influencing factors: Economic conditions, education quality, urbanization levels, and healthcare resources significantly impacted population mortality rates. Conclusion The present study identifies pronounced regional disparities in population health, providing a scientific basis for formulating targeted healthcare policies. Additionally, this study highlights the critical importance of spatial analysis in understanding and addressing public health issues to advance health equity.

Objective:To explore the anti-inflammatory effect and safety of two non-steroidal anti-inflammatory drugs in the phacoemulsification combined with intraocular lens (IOL) implantation.Methods:A randomized, double-blind, clinical trial was conducted.A total of 90 age-related cataract patients (90 eyes) who were diagnosed in Qingdao Eye Hospital Affiliated to Shandong First Medical University were enrolled from October 2020 to February 2021.The patients were randomized to diclofenac sodium group and bromofenac sodium group by random number table method, with 45 cases (45 eyes) in each group.All patients underwent phacoemulsification combined with IOL implantation, and 0.1% diclofenac sodium eye drops (preservative-free), 4 times a day, and 0.1% pramiphene eye drops, 2 times a day were applied in the perioperative period.The duration of continuous medication treatment and follow-up time were 6 weeks.The subjective symptoms of the patients were scored before and after surgery.The amount of tear fluid secretion was detected by Schirmer I test, and the tear film breakup time was recorded with the Oculus dry eye analyzer.Corneal fluorescein staining was observed under a slit lamp microscope with cobalt blue light.Anterior chamber flash was measured by slit-lamp biomicroscopy.The thickness of central macular area and the presence of macular cystoid edema was measured by optical coherence tomography.Visual acuity, noncontact intraocular pressure (IOP) and the drug safety were examined and evaluated.This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Qingdao Eye Hospital (No.[2020]60).All patients were informed about the surgery and postoperative medication and signed the informed consent form.Results:All subjects had no intraoperative complications, and completed treatment and follow-up as required.The preoperative, 1-day postoperative, 1-week postoperative, 6-week postoperative subjective symptom scores were (0.47±0.73), (0.56±0.62), (0.33±0.48), and (0.51±0.66) points in the diclofenac group, and (0.47±0.51), (0.75±0.61), (0.64±0.65), and (0.78±0.77) points in the bromfenac group.There were statistically significant differences in the subjective symptom scores at different time points between the two groups ( Fgroup=5.001, P=0.028; Ftime=2.920, P=0.035), and the subjective symptom scores of diclofenac sodium group were significantly lower than those of bromofenac sodium group (all at P<0.05).The preoperative, 1-week postoperative, 6-week postoperative tear secretion volume were (5.87±2.37), (6.07±2.53), and (6.29±0.25) mm in diclofenac sodium group, and (7.36±2.74), (6.29±3.46), and (5.80±2.76) mm in bromofenac sodium group.There was statistically significant difference in the tear secretion volume between the two groups before surgery ( F=6.910, P=0.012), but there was no significant difference on postoperative weeks 1 and 6 ( F=1.121, 0.772; P=0.729, 0.384).The preoperative, 1-week postoperative, 6-week postoperative non-invasive tear break-up time (NIBUT) were (8.00±6.28), (6.68±5.24), and (6.17±5.00) seconds in diclofenac sodium group, and (6.40±5.28), (4.50±2.46), and (5.39±5.39) seconds in bromofenac sodium group.There was no significant difference in NIBUT between the two groups ( Fgroup=3.415, P=0.068).There was significant difference in NIBUT within groups among different time points ( Ftime=4.358, P=0.020).The 1-day postoperative, 1-week postoperative, 6-week postoperative corneal epithelial staining score were (1.40±0.81), (0.13±0.34), (0.00±0.00) points in diclofenac sodium group, and (1.38±0.89), (0.22±0.47), and (0.00±0.00) points in bromofenac sodium group.There was no statistically significant difference in the corneal epithelial staining score between the two groups after surgery ( Fgroup=0.110, P=0.741).There were statistically significant differences in corneal epithelial staining scores within groups among different time points ( Ftime=175.054, P<0.01).The 1-day postoperative, 1-week postoperative, 6-week postoperative anterior chamber flare classification were 1.13±0.51, 0.13±0.34, and 0.00±0.00 in diclofenac sodium group, and 1.02±0.34, 0.16±0.37, and 0.00±0.00 in bromofenac sodium group.There was no significant difference in the overall anterior chamber flash between the two groups ( Fgroup=0.045, P=0.507).There were statistically significant differences in anterior chamber flash within groups among different time points ( Ftime=322.331, P<0.001).There was no significant difference in the preoperative and 6-week postoperative macular fovea thickness between both groups ( t=-0.221, -0.374; both at P>0.05).The incidence of macular cystoid edema 6 weeks after operation was 0% in both groups.Subjects tolerated the two tested drugs well.Eight adverse events occurred in this study, all of which were mild postoperative IOP elevation, including 3 in diclofenac sodium group with an incidence of 6.67% and 5 in bromofenac group with an incidence of 11.1%.IOP returned to normal in all the patients 1 week after stopping the use of drug. Conclusions:Two nonsteroidal anti-inflammatory drugs are safe and effective for anti-inflammatory treatment after cataract phacoemulsification combined with IOL implantation.The new diclofenac sodium eye drops are more comfortable than bromfenac sodium eye drops.

Objective To conduct data mining of asthma-inducing medications in underage populations based on the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database,so as to provide reference for the clinical application of related medications.Methods Adverse drug event(ADE)reports from the first quarter of 2013 to the fourth quarter of 2022 in the FAERS database were collected and screened for reports of asthma adverse events in the this population(under 18 years old),which were categorized into infants,toddlers,children,and adolescents according to different age groups,and were subjected to medication signal mining by using the reporting odds ratio method,the composite standardized method,and the information component method.Results A total of 1 915 reports were obtained after screening,involving 1 042(54.41％)males and 831(43.39％)females;the highest percentage of the reporting population was between 12 and under 18 years old,with a total of 762(39.79％);60.78％of the reports were reported by health professionals;and the results of the clinical referrals showed that serious adverse events occurred in 85.90％of the cases.306 suspected drugs were screened,52 drugs were determined to be valid signals,and 1 044 adverse events were reported,of which 16 drug inserts did not mention the risk of asthma,in order of elosulfatase alpha,canakinumab,tobramycin,vancomycin,ceftriaxone,cetirizine,phenylephrine,imiglucerase,cefuroxime,betamethasone,atropine,tadalafil,riscovastatin,cyclophosphamide,octreotide,and omeprazole.Conclusion The FAERS database was mined for adverse drug event signals and evaluated using the proportional disequilibrium method to identify 16 medicines that may trigger pharmacogenetic asthma and are not documented in the specification,which can be used to provide a good early warning for the clinic.At the same time,focusing on special populations,strengthening the assessment of lung function before medication and monitoring during and after medication,timely interventions were taken to reduce the harm of drug-derived adverse reactions and ensure the safe use of medication.

Objective Based on the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database,data mining was conducted on hematological adverse events related to antibody drug conjugates(ADC),providing reference for the safe use of ADC drugs in clinical practice.Methods The report data from the third quarter of 2011 to the fourth quarter of 2022 were retrieved from the FAERS database.After data cleaning such as deduplication and name standardization,extract hematological adverse events related to ADC,and use report odds ratio method and the information component method for signal detection.Results A total of 101 610 adverse event reports were extracted,with 8 ADC drugs as the primary suspected drugs,and 5 768 ADC related hematological adverse event reports.Among them,3 423 cases of agranulocytosis were involved,and the signal intensity from strong to weak were sacituzumab govitecan(SG),gemtuzumab ozogamicin(GO),brentuximab vedotin(BV),polatuzumab vedotin(PV),enfortumab vedotin(EV),trastuzumab deruxtecan(TD),inotuzumab ozogamicin(IO)and ado-trastuzumab emtansine(TDM-1).There were 2 327 cases hematopoietic cell deficiency,with signals ranging from strong to weak were IO,SG,BV,EV,PV,TD,TDM-1,and GO.Report with clinical outcome of death of ADC drug related hematological adverse events included BV 179(16.84％),TDM-1 102(13.01％),TD 88(27.08％),GO 12(16.90％),IO 8(11.59％),EV 54(24.32％),PV 22(27.16％),and SG 84(21.05％).Adverse event time analysis showed that the number of events on the first day of TD,IO,and SG medication accounts for ≥ 40％of the total number of cases.The median time of hematological adverse events in TD,GO,IO,EV,PV,and SG was within one treatment course(21 days).Conclusion Attention should be paid to the risk of ADC drug-related hematological adverse event,during the clinical medication process,blood cell count changes should be closely monitored,and any abnormalities should be promptly diagnosed and treated.

Objective Studies on the relationship between iodine,vitamin A(VA),and vitamin D(VD)and thyroid function are limited.This study aimed to analyze iodine and thyroid-stimulating hormone(TSH)status and their possible relationships with VA,VD,and other factors in postpartum women. Methods A total of 1,311 mothers(896 lactating and 415 non-lactating)from Hebei,Zhejiang,and Guangxi provinces were included in this study.The urinary iodine concentration(UIC),TSH,VA,and VD were measured. Results The median UIC of total and lactating participants were 142.00 μg/L and 139.95 μg/L,respectively.The median TSH,VA,and VD levels in all the participants were 1.89 mIU/L,0.44 μg/mL,and 24.04 ng/mL,respectively.No differences in the UIC were found between lactating and non-lactating mothers.UIC and TSH levels were significantly different among the three provinces.The rural UIC was higher than the urban UIC.Obese mothers had a higher UIC and a higher prevalence of excessive TSH.Higher UICs and TSHs levels were observed in both the VD deficiency and insufficiency groups than in the VD-sufficient group.After adjustment,no linear correlation was observed between UIC and VA/VD.No interaction was found between vitamins A/D and UIC on TSH levels. Conclusion The mothers in the present study had no iodine deficiency.Region,area type,BMI,and VD may be related to the iodine status or TSH levels.

Objective The purpose of this study was to investigate the bacterial communities of biting midges and ticks collected from three sites in the Poyang Lake area,namely,Qunlu Practice Base,Peach Blossom Garden,and Huangtong Animal Husbandry,and whether vectors carry any bacterial pathogens that may cause diseases to humans,to provide scientific basis for prospective pathogen discovery and disease prevention and control. Methods Using a metataxonomics approach in concert with full-length 16S rRNA gene sequencing and operational phylogenetic unit(OPU)analysis,we characterized the species-level microbial community structure of two important vector species,biting midges and ticks,including 33 arthropod samples comprising 3,885 individuals,collected around Poyang Lake. Results A total of 662 OPUs were classified in biting midges,including 195 known species and 373 potentially new species,and 618 OPUs were classified in ticks,including 217 known species and 326 potentially new species.Surprisingly,OPUs with potentially pathogenicity were detected in both arthropod vectors,with 66 known species of biting midges reported to carry potential pathogens,including Asaia lannensis and Rickettsia bellii,compared to 50 in ticks,such as Acinetobacter lwoffii and Staphylococcus sciuri.We found that Proteobacteria was the most dominant group in both midges and ticks.Furthermore,the outcomes demonstrated that the microbiota of midges and ticks tend to be governed by a few highly abundant bacteria.Pantoea sp7 was predominant in biting midges,while Coxiella sp1 was enriched in ticks.Meanwhile,Coxiella spp.,which may be essential for the survival of Haemaphysalis longicornis Neumann,were detected in all tick samples.The identification of dominant species and pathogens of biting midges and ticks in this study serves to broaden our knowledge associated to microbes of arthropod vectors. Conclusion Biting midges and ticks carry large numbers of known and potentially novel bacteria,and carry a wide range of potentially pathogenic bacteria,which may pose a risk of infection to humans and animals.The microbial communities of midges and ticks tend to be dominated by a few highly abundant bacteria.

Human brain banks use a standardized protocol to collect,process and store post-mortem human brains and related tissues,along with relevant clinical information,and to provide the tissue samples and data as a resource to foster neuroscience research according to a standardized operating protocols(SOP).Human brain bank serves as the foundation for neuroscience research and the diagnosis of neurological disorders,highlighting the crucial rule of ensuring the consistency of standardized quality for brain tissue samples.The first version of SOP in 2017 was published by the China Human Brain Bank Consortium.As members increases from different regions in China,a revised SOP was drafted by experts from the China Human Brain Bank Consortium to meet the growing demands for neuroscience research.The revised SOP places a strong emphasis on ethical standards,incorporates neuropathological evaluation of brain regions,and provides clarity on spinal cord sampling and pathological assessment.Notable enhancements in this updated version of the SOP include reinforced ethical guidelines,inclusion of matching controls in recruitment,and expansion of brain regions to be sampled for neuropathological evaluation.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

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.