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.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive dysfunction and behavioral impairment, and there is a lack of effective drugs to treat AD clinically. Existing medications for the treatment of AD, such as Tacrine, Donepezil, Rivastigmine, and Aducanumab, only serve to delay symptoms and but not cure disease. To add insult to injury, these medications are associated with very serious adverse effects. Therefore, it is urgent to explore effective therapeutic drugs for AD. Recently, studies have shown that a variety of enzyme inhibitors, such as cholinesterase inhibitors, monoamine oxidase (MAO)inhibitors, secretase inhibitors, can ameliorate cholinergic system dysfunction, Aβ production and deposition, Tau protein hyperphosphorylation, oxidative stress damage, and the decline of synaptic plasticity, thereby improving AD symptoms and cognitive function. Some plant extracts from natural sources, such as Umbelliferone, Aaptamine, Medha Plus, have the ability to inhibit cholinesterase activity and act to improve learning and cognition. Isochromanone derivatives incorporating the donepezil pharmacophore bind to the catalytic active site (CAS) and peripheral anionic site (PAS) sites of acetylcholinesterase (AChE), which can inhibit AChE activity and ameliorate cholinergic system disorders. A compound called Rosmarinic acid which is found in the Lamiaceae can inhibit monoamine oxidase, increase monoamine levels in the brain, and reduce Aβ deposition. Compounds obtained by hybridization of coumarin derivatives and hydroxypyridinones can inhibit MAO-B activity and attenuate oxidative stress damage. Quinoline derivatives which inhibit the activation of AChE and MAO-B can reduce Aβ burden and promote learning and memory of mice. The compound derived from the combination of propargyl and tacrine retains the inhibitory capacity of tacrine towards cholinesterase, and also inhibits the activity of MAO by binding to the FAD cofactor of monoamine oxidase. A series of hybrids, obtained by an amide linker of chromone in combine with the benzylpiperidine moieties of donepezil, have a favorable safety profile of both cholinesterase and monoamine oxidase inhibitory activity. Single domain antibodies (such as AAV-VHH) targeted the inhibition of BACE1 can reduce Aβ production and deposition as well as the levels of inflammatory cells, which ultimately improve synaptic plasticity. 3-O-trans-p-coumaroyl maslinic acid from the extract of Ligustrum lucidum can specifically inhibit the activity of γ-secretase, thereby rescuing the long-term potentiation and enhancing synaptic plasticity in APP/PS1 mice. Inhibiting γ-secretase activity which leads to the decline of inflammatory factors (such as IFN-γ, IL-8) not only directly improves the pathology of AD, but also reduces Aβ production. Melatonin reduces the transcriptional expression of GSK-3β mRNA, thereby decreasing the levels of GSK-3β and reducing the phosphorylation induced by GSK-3β. Hydrogen sulfide can inhibitGSK-3β activity via sulfhydration of the Cys218 site of GSK-3β, resulting in the suppression of Tau protein hyperphosphorylation, which ameliorate the motor deficits and cognitive impairment in mice with AD. This article reviews enzyme inhibitors and conformational optimization of enzyme inhibitors targeting the regulation of cholinesterase, monoamine oxidase, secretase, and GSK-3β. We are hoping to provide a comprehensive overview of drug development in the enzyme inhibitors, which may be useful in treating AD.

Microorganisms can form biofilms, complex, heterogeneous, multicellular communities that adhere to surfaces. Biofilm formation on the surface of structures in water will accelerate structures’ corrosion, seriously affect their service efficiency and life, and significantly impact the growth of animals, plants, and human life. Hence, clarifying the mechanism of biofilm formation contributes to developing new strategies to control biofilm formation on surface and then reduce infections, biofouling, and contaminations. Biofilm-targeting strategies include the regulation of established biofilms or the modulation of single-cell attachment. In most studies, physicochemical mechanism is frequently applied to explain the initial bacterial adhesion phenomena but rarely to explain other stages of biofilm formation. This review presents a five-step comprehensive description of the physicochemical process from film formation to biofilm maturation: (1) period of film formation; (2) period of bacterial adhesion; (3) period of extracellular-polymeric-substances (EPSs) membrane formation; (4) period of regulating biofilm by quorum sensing (QS); (5) period of biofilm maturation. We first clarify how the film formed by compound molecules affects the surface’s physicochemical properties and initial adhesion, summarizing many factors that affect bacterial adhesion. We then review the types of EPSs and signal molecules secreted by bacteria after irreversible adhesion, as well as their role and QS mechanism in biofilm maturation. Finally, we discuss how bacteria or microcolonies separate from the mature biofilm by physicochemical action and summarize the morphology and adhesion characterization methods after the biofilm matures. This review redefines the role of physicochemical in the whole process of biofilm formation and provides a theoretical basis for the prevention, removal, and utilization of biofilm and other related research fields.

During the progression of heart failure(HF),abnormal transduction of the transforming growth factor-β(TGF-β)/Smads signaling pathway is important mechanism of myocardial fibrosis(MF)in HF.TGF-β,a key factor in MF,is in an overexpression state in the process of MF in HF,and Smads is a major effector downstream of TGF-β.The TGF-β/Smads pathway induces abnormal proliferation of myofibroblasts,aggravates myocardial extracellular matrix deposition,and reduces the ability of the cardiac tissues to resist fibrosis,which plays a complex role in the pathogenesis of MF in HF.Traditional Chinese medicine(TCM)has the efficacy of unequivocal inhibiting myocardial collagen deposition,anti-MF,protecting the myocardium and improving cardiac function in the prevention and treatment of MF in HF and so on,and the TGF-β/Smads pathway is one of the key pathways through which TCM monomers,TCM combinations,and proprietary medicines can exert their cardioprotective effects on the HF.This paper reviews the existing experimental research results of TCM intervening in the TGF-β/Smads pathway for the treatment of MF in HF over the past 10 years,with a view to providing theoretical basis for the prevention and treatment of HF MF well as the development and of new drugs.

Purpose/Significance To provide reference for the information technology laboratory management in universities and col-leges of traditional Chinese medicine(TCM).Method/Process The paper focuses on the main problems faced by information technology laboratory management in universities and colleges of TCM,and proposes ideas of informatization path selection based on practices in Hu-bei University of Chinese Medicine.It constructs informatization management system from the following aspects:network foundation of in-formation technology laboratory,terminal protection cloud service,internet of things technology application,laboratory opening,experi-mental teaching resource sharing,etc.Result/Conclusion The informatization management system significantly improves the utilization rate of the laboratory,greatly reduces the personnel cost and time cost.

Objective To clarify the high-touch surface in oral diagnosis and treatment procedures,provide basis and guidance for cleaning and disinfection.Methods The direct observation method was used to investigate the tou-ch time and frequency of environmental surfaces in 7 outpatient departments of a tertiary stomatology hospitals in Beijing.The average touch frequency,95％confidence interval and cumulative touch rate were calculated.Results In oral diagnosis and treatment procedures,the average touch frequency of the environmental surface was 26.75 times per procedure,with the highest in endodontics(46.25 times per procedure)and the lowest in the oral mucosal specialty(10.19 times per procedure).The high-touch surface consisted of the shadowless lamp handle,manipula-tion panel and handle on dental unit(doctor's side),computer keyboard and mouse,handle and line front end of three way syringe,as well as dental high speed handpiece and line front end,with average touch frequencies of 3.99,3.85,2.65,1.86,and 1.40 times per procedure.The high-touch surface in all stomatology specialties in-cluded the manipulation panel and handle on dental unit(doctor's side),75％of specialties included computer key-board and mouse,and the shadowless lamp handle has the highest touch frequency in 50％of specialties.The ave-rage touch frequency of the environmental surface was highest(113.50 times per procedure)during crown prepara-tion procedure,and the lowest(8.50 times per procedure)during the orthodontic consultations.Conclusion The high-touch surface of different dental specialties and different diagnosis and treatment procedures are different.Me-dical institutions should take corresponding cleaning,disinfection and management measures according to the actual situation of high-touch surface in stomatology departments,so as to effectively improve the quality of environmental cleaning and disinfection.

This study investigated the etiological characteristics and whole genome sequencing of clostridium perfringens (CP) from a food poisoning outbreak. Multiplex real-time PCR was employed to screen pathogens in collected samples. Based on the preliminary screening results, the isolation, cultivation, and identification of suspected pathogenic CP bacteria were performed. The nucleic acid tests were conducted for CP-related virulence genes on CP isolates, anal swab specimens and food samples. The molecular typing of CP isolates was analyzed by using pulsed-field gel electrophoresis (PFGE). A phylogenetic tree was established to analyze nucleotide and amino acid homology after sequencing the PLC gene. The whole genome sequencing and gene annotation on the representative strain QD2022FB4-CP4 were performed to explore its drug resistance, toxin genes and biological characteristics. The analysis revealed that the food poisoning was triggered by F-type Clostridium perfringens, which infected the consumers by contaminating‘roujiamo’ sandwiches. The whole genome sequencing of the strain QD2022FB4-CP found that it had active metabolic processes, multiple virulence genes and multidrug resistance characteristics.

Objective:To investigate the correlation between nutritional status and quality of life in inpatients with nasopharyngeal carcinoma and to analyze the factors affecting nutritional status,so as to provide evidence for clinical nutritional support treatment.Methods:In this study,we retrospectively collected data from patients with nasopharyngeal carcinoma who met the inclusion and exclusion criteria in the Head and Neck Oncology Department of Zunyi Medical University Affiliated Hospital from 2014 to 2019.The NRS 2002 scale was used for nutritional risk screening,the PG-SGA scale for nutritional status assessment and the EORTCQLQ-C30 V3.0 scale for quality of life assessment.To further explore the correlation between nutritional status and quality of life,as well as the factors affecting nutritional status.Results:A total of 216 patients were collected,including 168 male(77.78%);average age(50.5±10.58)years;26.85%were at nutritional risk(NRS 2002 score≥3);28.70%were moderate malnutrition(PG-SGA score 4-8),and 23.15%were severe malnutrition(PG-SGA score≥9).There were significant differences in several physical examinations(such as body weight,body mass index,muscle circumference at the midpoint of the upper arm,etc.)and blood biochemical indexes(such as prealbumin,neutrophils,urea nitrogen,etc.)of patients with different nutritional status were differed between groups(P<0.05).Univariate analysis showed that age≥65 years was a risk factor for the development of severe malnutrition(OR:3.429,95%CI:1.467 to 8.014,P=0.004),whereas a high level of education(senior high school and above)was a protective factor(OR:0.027,95%CI:0.011 to 0.064,P=0.000).The poorer the nutritional status of nasopharyngeal carcinoma patients,the lower the quality of life.Conclusion:Nasopharyngeal carcinoma patients have a high incidence of malnutrition;the poorer the nutritional status of the patient,the lower the quality of life;routine nutritional diagnosis and treatment of nasopharyngeal carcinoma patients after admission to the hospital is recommended to improve clinical outcomes.

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 The DNA methylation microhaplotype(DMH)refers to the combination of multiple methylation sites within a very short range,and these haplotypes show wide diversity.We carried out screening and validation of age-related DMHs in mouse blood.Methods We initially constructed a theoretical dataset of DMHs based on the mouse reference genome.We then screened age-related DMHs by Spearman's rank correlation analysis,using high-throughput sequencing information for DNA methylation in mouse blood from a network database.Finally,cross-validation was performed using a validation dataset.Results A total of 6787 142 DMH sites were identified within 50 bp in the mouse genome,including 98.64%of single-digit CpG sites.A total of 5835 age-associated DMHs were screened in 58 mouse blood samples(|rho|＞0.5,P＜0.01),accounting for 0.086%of DMHs.Finally,we validated the top 100 age-associated DMHs with high correlation in 95 independent samples,Resultsing in 44 loci.Conclusions The age-associated DMHs screened in this study may be useful in future studies of apparent age prediction using mouse blood and in aging studies.