Alzheimer's disease(AD)is one of the most common types of dementia in clinical practice.The increased permeability of the gut and blood-brain barrier caused by intestinal microecological dysbiosis may be an important incentive to affect the incidence of AD.Gut microbiota regulates the central nervous system through the gut microbiota-gut-brain axis(gut-brain axis),and plays an important role in the cognitive func-tion,occurrence and development of clinical symptoms in AD patients.This review comprehensively reviewed the current literature on the relationship between gut microbiota dysregulation and inflammatory cytokine changes in AD,and the treatment of AD targeting with gut microbiota,so as to clarify the new progress in the influence of intestinal microecology changes on the cognitive function of AD patients,the potential diagnosis in the early onset of AD,and the potential mechanism of gut microbiota participating in the regulation of AD.It provides a new idea for the treatment strategy of AD.

Inflammatory bowel disease(IBD)is a chronic inflammatory disease of the gastrointestinal tract that includes Crohn's disease and ulcerative colitis.IBD may be caused by complex interactions between genetic susceptibility,environmental factors,and alterations in the gut microbiota,resulting in dysregulated innate and adaptive immune responses.Recent studies have identified macrophages in the intestinal inflammatory response as having the plasticity to not only regulate inflammation,but also to promote tissue repair and healing.As aberrant macrophage polarization occurs during the development of IBD,the balance between the phenotype and function of pro-inflammatory M1 and anti-inflammatory M2 macrophages is regulated by extracellular and intracellular stimuli,and this process is therefore expected to be a potential target for new therapeutic approaches.This article reviewed the progress of research on macrophage polarization in IBD.

Objective:To investigate an association between glycosylated hemoglobin(HbA1c)level and non-alcoholic fatty liver(NAFL)in the elderly.Methods:In this retrospective case-control study, 5 186 elderly individuals aged 65 years and over meeting the inclusion conditions via health physical examination were successively selected from January to December 2018.They were divided into NAFL group(n=1 731)and non-NAFL group(n=3 455). Waist circumference, body mass index, smoking history, diastolic blood pressure, glomerular filtration rate, serum levels of triglyceride, low density lipoprotein cholesterol, alanine aminotransferase, aspartic aminotransferase, fasting blood glucose and HbA1c were compared between the two groups, and their correlations with NAFL were analyzed.Results:The prevalence of NAFL was 33.4%(1, 731/5, 186). The values of waistline, body mass index, smoking history, diastolic blood pressure, triglyceride, total cholesterol, low density lipoprotein cholesterol, glomerular filtration rate, alanine aminotransferase, aspartate aminotransferase, fasting glucose and HbA1c were higher in the NAFL group than in non-NAFL group(all P<0.05). While levels of creatinine, urea nitrogen and age were lower in the NAFL group than in non-NAFL group( P<0.05). According to the quartile of HbA1c level, these subjects were divided into Q1 to Q4 groups(HbA1c<5.7%, 5.7≤HbA1c<6.0%, 6.0%≤HbA1c<6.5%, HbA1c≥6.5%), and the prevalence of NAFL in the Q1 to Q4 were 22.8%(225/1 120), 27.9%(398/1 429), 36.5%(514/1 409), 45.9%(564/1 228)respectively.The prevalence of NAFL was increased along with the increase in the level of HbA1c( P<0.01). Multivariate Logistic regression analysis showed that after adjusting for age, gender and metabolic components, the risk for developing NAFL was gradually increased in Q2 group, Q3 group, Q4 group versus Q1 group as the following OR value: OR=1.274, 95% CI: 1.004-1.616; OR=1.639, 95% CI: 1.294-2.077; OR=1.787, 95% CI: 1.337-2.389, respectively, all P<0.01. Conclusions:The prevalence of NAFL is positively associated with HbA1c levels in the elderly and HbA1c is an independent risk factor for NAFL disease.

Objective: To investigate the characteristics of hemolysis, resistance and homology of Staphylococcus cohnii urealyticum. Methods: A retrospective study was carried out on thirteen clinical strains of Staphylococcus cohnii urealyticum. They were re-identified by MALDI-TOF MS. Their colony and hemolytic characteristics on blood agar plates were observed. The co-hemolysis between Staphylococcus cohnii urealyticum and Staphylococcus aureus was demonstrated. The hemolysin genes and drug resistance genes were detected by PCR. Pulsed field gel electrophoresis and mass spectrometry were used to analyze the homology of strains. The susceptibility of strains to antimicrobial agents was detected by agar dilution. Results: The confirmed 13 strains of Staphylococcus cohnii urealyticum showed various levels of hemolysis and had enhanced synergistic hemolysis with Staphylococcus aureus. All strains were susceptible to vancomycin and tigecycline. There were 12 strains which carried mecA gene, 7 strains carried cfr gene, 7 strains carried ermC gene. The 13 strains were divided into 3 groups by MALDI-TOF MS, and 6 types by pulsed field gel electrophoresis. Conclusions Clinical strains of Staphylococcus cohnii urealyticum demonstrated various levels of hemolysis which could be enhanced by Staphylococcus aureus. Although they carried different drug resistance genes, they were all susceptible to vancomycin and tigecycline.

Objective To examine the clinical value of polymerase chain reaction (PCR) in rapid diagnosis of bacterial and fungal infection of central nervous system.Methods The cerebrospinal fluid (CSF) samples were collected from 137 patients for DNA extraction.PCR was used to amplify the DNA of pathogenic bacteria and fungi using universal primers.The PCR products were subjected to DNA sequencing analysis for identifying microbial species.The conventional culture of pathogens was carried out simultaneously as control.Results PCR revealed bacterial pathogen in 50 of the 137 CSF samples,fungal pathogen in 6 of the 137 CSF samples.Conventional culture of CSF reported positive bacterial infection in 38 cases,fungal infection in 5 cases.PCR provided diagnostic sensitivity of 40.9％,specificity 100％,positive predictive value 100％,negative predictive value 38.2％.The diagnostic efficiency was 56.7％.In contrast,the conventional culture achieved the results of 31.4％,100％,100％,34.7％,44.4％,respectively.The sensitivity,negative predictive value,and diagnostic efficiency of PCR were significantly better than conventional culture method.The coincidence rate between PCR and conventional culture was 97.7％.Conclusions Universal primer-based PCR is characteristic of short turnaround time,specificity,sensitivity and accuracy,which is very useful for rapid diagnosis of the pathogenic bacteria and fungi in central nervous system infections.

Objective To evaluate the value of amplification and sequencing of 16S rRNA gene in the identification of clinical rare pathogenic bacteria,and guide the diagnosis and treatment for related clinical infection.Methods 12 bacterial isolates that were difficult,or unable to be identified with conventional laboratory methods,or with special phenotypes were collected. The 16S rRNA gene was amplified by polymerase chain reaction (PCR),then sequenced for identifying bacterial species through BLAST comparison,clinical characteristics of related infection were ana-lyzed.Results 12 clinical isolates were all positive for PCR amplification (about 1500 bp),species were all identi-fied (similarity≥99% ),the identified strains were Listeriamonocytogenes(n= 2),Brucellamelitensis(n= 2),Fu-sobacteriummortiferum(n= 1),Rothiaaeria(n= 1),Nocardiafarcinica(n= 1),Staphylococcussaccharolyticus (n= 1 ),Rhizobiumradiobacter(n= 1 ),Prevotellabivia(n= 1 ),Ralstoniamannitolilytica(n= 1 ),and Atopobium vaginae(n= 1 ). The sensitivity of 16S rRNA gene amplification was high,and the minimum detection limit of Escherichiacoli ATCC 25922 was 1.5×101 CFU/mL. Clinical data of 12 patients revealed that these strains can cause multi-sites and multi-types of infection,after patients received targeted antimicrobial therapy,11 improved, and 1 died.Conclusion Sequencing for 16S rRNA gene can rapidly and accurately identify rare,anaerobic,and difficult cultured bacteria,provide laboratory evidence for etiological diagnosis and treatment of different types of infection.

Objective To understand pathogen spectrum of bacterial and fungal infection of central nervous system (CNS),and evaluate the etiological diagnostic value of universal primer polymerase chain reaction (PCR).Methods Data about patients with suspected or confirmed bacterial and fungal infection of CNS from January 2009 to March 2015 were collected,species of pathogens from cerebrospinal fluid (CSF)were analyzed,DNA from patients’CSF were performed PCR amplification and sequencing with universal primers of bacterial 16S rRNA and fungal 28S rRNA, PCR detection results were compared with CSF culture during the same period.Results A total of 400 patients were with confirmed or suspected bacterial or fungal infection of CNS,132 of whom were with positive CSF culture.150 pathogenic isolates were detected,including 48 isolates of gram-positive bacteria,90 gram-negative bacteria,and 12 fungi;the top three isolated bacteria were Acinetobacter baumannii (n =32 ),coagulase negative staphylococcus (n=16)and Klebsiella pneumoniae (n=13);the most common fungus was Cryptococcus neoformans (n=8).CSF from 88 infected patients and 20 non-infected patients were selected for PCR amplification,the sensitive of PCR am-plification assay was higher than the culture method (35.23% [31/88]vs 28.41 %[25/88],χ2 =4.17,P <0.05).

Objective To investigate the distribution and antimicrobial resistance of pathogens isolated from surgi-cal patients with infection.Methods Distribution and antimicrobial resistance of 1 208 pathogens isolated from sur-gical patients with infection from January 2013 to January 2014 were analyzed retrospectively.Results Of 1 208 pathogenic isolates,gram-negative bacteria,gram-positive bacteria and fungi accounted for 64.57% (n = 780 ), 24.92%(n = 301 )and 10.51 % (n = 127 )respectively.The main specimens were sputum (44.78%),urine (21 .11 %),blood(11 .51 %),and pus(10.26%).Antimicrobial susceptibility testing results showed that the produ-cing rate of extended-spectrumβ-lactamases (ESBLs)of Escherichia coli and Klebsiella pneumoniae was 62.60%and 33.61 % respectively,resistant rate to imipenem was 0.76% and 15.57%,respectively.The resistant rate of Pseudomonas aeruginosa and Acinetobacter baumannii to imipenem was 38.93% and 75.80% respectively.Methi-cillin-resistant Staphylococcus aureus and methicillin-resistant coagulase negative Staphylococcus was 71 .68% and 87.93% respectively.Conclusion The major pathogens isolated from surgical patients with infection are gram-neg-ative bacteria,the main infection sites are respiratory tract and urinary tract in this hospital;multidrug resistance is serious,especially carbapenem resistance,which should be paid attention.

OBJECTIVE To determine the feasibility of clindamycin-loaded calcium phosphate cement(CLCPC) as a local antibiotic delivery system.METHODS The initial setting time(tI) and the final setting time(tF) were measured for 0%,2% and 5% CLCPC according to ASTM C266-89 method.Clindamycin concentrations eluting from the samples of 2% and 5% CLCPC in PBS were analyzed by HPLC at different times.The bacteriostasis tests were done by plate diffusion method for 2% and 5% CLCPC and 2% Palacos R-40 bone cement(PMMP) samples,and the diameters of the bacteriostasis ring and bacteriostasis duration were observed.The setting product and crystal size of 0%,2% and 5% CLCPC were analyzed and observed by X-ray diffraction(XRD) and scanning electron microscopy(SEM).RESULTS The setting time could be shortened by adding clindamycin(tI,tF) of 2% and 5% CLCPC.Clindamycin was with burst-release from CLCPC within the intial 6-hour period and the release rate slowed down on 4th day.Clindamycin could still release until to the 42th day.The ring of 2% Palacos R-40 bone cement(PMMP) bacteriostasis was smaller than that of 2% CLCPC,and the ring of 2% CLCPC bacteriostasis was smaller than that of 5%CLCPC.The bacteriostasis still existed to the 42th day of test for 2% and 5%CLCPC and 2% Clindamycin-loaded Palacos R-40 bone cement(CLPMMP).From the 30th day,many bacterial colonies were seen in the culture media laying 2%CLPMMP sample.On the contrary,bacterial colony was not found in the media putting 2% and 5%CLCPC.XRD and SEM showed that clindamycin did′t have an influence on setting product,crystal size and structure of CPC.CONCLUSIONS Clindamycin-loaded calcium phosphate cement can be used as a local antibiotic delivery system.

OBJECTIVE To establish the implanted biofilm model of rabbit implant infection.METHODS SEP was cultured,purified,identified,and tested for the drug sensitivity and the biofilm production.Healthy adult rabbits were randomly divided into 4 groups,8 in each group.The stainless steel screws and washer UHMWPEs were implanted into the femoral condyle of the non-articular surface of the rabbit right stifle knee.The knee joints were inoculated with 1ml sterile saline,102,103 and 104 CFU SEP,respectively.Wounds were observed postoperatively.After the 14th days postoperation,the knee synovium of 32 rabbits sacrificed were taken out by aseptic technique and were cultured to determine whether the knees were infected and which concentration of SEP was the appropriate for causing knee joint infection.UHMWPEs from the appropriate ID group were observed to find whether there were biofilms on the surface by SEM and LCSM.RESULTS The bacterial strain was identified as SEP and could produce biofilm.Among the knee joints inoculated with 1ml saline,102,103 and 104 CFU SEP,the infective rate was 0,37.5%,100.0% and 100.0% and poor wound healing was in 0,1,2 and 4 rabbits,respectively.It showed 103 CFU of SEP was the appropriate ID.Biofilms were found on all UHMWPE surfaces from 103 CFU SEP group by SEM and LCSM.SEM showed SEP in the biofilms on the surface of UHMWPE was agglomerated and wrapped in the matrix.The structure of biofilms in which SEP radiated red fluorescence was inlaid in mucopolysaccharide stained green fluorescence was observed by LCSM.CONCLUSIONS The model provides an effective method to investigate the biofilm.