Interferon-γpriming enhances the therapeutic effects of menstrual blood-derived stromal cells in a mouse liver ischemia-reperfusion model

BACKGROUND Mesenchymal stem cells(MSCs)have been used in liver transplantation and have certain effects in alleviating liver ischemia-reperfusion injury(IRI)and regulating immune rejection.However,some studies have indicated that the effects of MSCs are not very significant.Therefore,approaches that enable MSCs to exert significant and stable therapeutic effects are worth further study.AIM To enhance the therapeutic potential of human menstrual blood-derived stromal cells(MenSCs)in the mouse liver ischemia-reperfusion(I/R)model via interferon-γ(IFN-γ)priming.METHODS Apoptosis was analyzed by flow cytometry to evaluate the safety of IFN-γpriming,and indoleamine 2,3-dioxygenase(IDO)levels were measured by quantitative real-time reverse transcription polymerase chain reaction,western blotting,and ELISA to evaluate the efficacy of IFN-γpriming.In vivo,the liver I/R model was established in male C57/BL mice,hematoxylin and eosin and TUNEL staining was performed and serum liver enzyme levels were measured to assess the degree of liver injury,and regulatory T cell(Treg)numbers in spleens were determined by flow cytometry to assess immune tolerance potential.Metabolomics analysis was conducted to elucidate the potential mechanism underlying the regulatory effects of primed MenSCs.In vitro,we established a hypoxia/reoxygenation(H/R)model and analyzed apoptosis by flow cytometry to investigate the mechanism through which primed MenSCs inhibit apoptosis.Transmission electron microscopy,western blotting,and immunofluorescence were used to analyze autophagy levels.RESULTS IFN-γ-primed MenSCs secreted higher levels of IDO,attenuated liver injury,and increased Treg numbers in the mouse spleens to greater degrees than untreated MenSCs.Metabolomics and autophagy analyses proved that primed MenSCs more strongly induced autophagy in the mouse livers.In the H/R model,autophagy inhibitors increased the level of H/R-induced apoptosis,indicating that autophagy exerted protective effects.In addition,primed MenSCs decreased the level of H/R-induced apoptosis via IDO and autophagy.Further rescue experiments proved that IDO enhanced the protective autophagy by inhibiting the mammalian target of rapamycin(mTOR)pathway and activating the AMPK pathway.CONCLUSION IFN-γ-primed MenSCs exerted better therapeutic effects in the liver I/R model by secreting higher IDO levels.MenSCs and IDO activated the AMPK-mTOR-autophagy axis to reduce IRI,and IDO increased Treg numbers in the spleen and enhanced the MenSC-mediated induction of immune tolerance.Our study suggests that IFN-γ-primed MenSCs may be a novel and superior MSC product for liver transplantation in the future.

An Evaluation Method of Human Gut Microbial Homeostasis by Testing Specific Fecal Microbiota

Research on microecology has been carried out with broad perspectives in recent decades,which has enabled a better understanding of the gut microbiota and its roles in human health and disease.It is of great significance to routinely acquire the status of the human gut microbiota;however,there is no method to evaluate the gut microbiome through small amounts of fecal microbes.In this study,we found ten predominant groups of gut bacteria that characterized the whole microbiome in the human gut from a large-sample Chinese cohort,constructed a real-time quantitative polymerase chain reaction(qPCR)method and developed a set of analytical approaches to detect these ten groups of predominant gut bacterial species with great maneuverability,efficiency,and quantitative features.Reference ranges for the ten predominant gut bacterial groups were established,and we found that the concentration and pairwise ratios of the ten predominant gut bacterial groups varied with age,indicating gut microbial dysbiosis.By comparing the detection results of liver cirrhosis(LC)patients with those of healthy control subjects,differences were then analyzed,and a classification model for the two groups was built by machine learning.Among the six established classification models,the model established by using the random forest algorithm achieved the highest area under the curve(AUC)value and sensitivity for predicting LC.This research enables easy,rapid,stable,and reliable testing and evaluation of the balance of the gut microbiota in the human body,which may contribute to clinical work.

Selective intestinal decontamination for the prevention of early bacterial infections after liver transplantation

Bacterial infection in the first month after liver transplantation is a frequent complication that poses a serious risk for liver transplant recipients as contributes substantially to increased length of hospitalization and hospital costs being a leading cause of death in this period. Most of these infections are caused by gramnegative bacilli, although gram-positive infections, especially Enterococcus sp. constitute an emerging infectious problem. This high rate of early postoperative infections after liver transplant has generated interest in exploring various prophylactic approaches to surmount this problem. One of these approaches is selective intestinal decontamination(SID). SID is a prophylactic strategy that consists of the administration of antimicrobials with limited anaerobicidal activity in order to reduce the burden of aerobic gram-negative bacteria and/or yeast in the intestinal tract and so prevent infections caused by these organisms. The majority of studies carried out to date have found SID to be effective in the reduction of gram-negative infection, but the effect on overall infection is limited due to a higher number of infection episodes by pathogenic enterococci and coagulase-negative staphylococci. However, difficulties in general extrapolation of the favorable results obtained in specific studies together with the potential risk of selection of multirresistant microorganisms has conditioned controversy about the routinely application of these strategies in liver transplant recipients.

Fluoroquinolones for the treatment of latent Mycobacterium tuberculosis infection in liver transplantation

Solid organ transplantation(SOT)is the best treatment option for end-stage organ disease.Newer immunosuppressive agents have reduced the incidence of graft rejection but have increased the risk of infection,particularly due to the reactivation of latent infections due to opportunistic agents such as Mycobacterium tuberculosis.Active tuberculosis(TB)after SOT is a significant cause of morbidity and mortality.Most cases of posttransplant TB are secondary to reactivation of latent tuberculosis infection(LTBI)due to the effects of long-term immunosuppressive therapy.Risk minimization strategies have been developed to diagnose LTBI and initiate treatment prior to transplantation.Isoniazid with vitamin B6 supplementation is the treatment of choice.However,liver transplantation(LT)candidates and recipients have an increased risk of isoniazid-induced liver toxicity,leading to lower treatment completion rates than in other SOT populations.Fluoroquinolones(FQs)exhibit good in vitro antimycobacterial activity and a lower risk of drug-induced liver injury than isoniazid.In the present review,we highlight the disease burden posed by posttransplant TB and summarize the emerging clinical evidence supporting the use of FQs for the treatment of LTBI in LT recipients and candidates.

Epidemiology and clinical features of cystic hydatidosis in Western Sicily:A ten-year review

AIM:To assess retrospectively the epidemiological and clinical aspects of cystic echinococcosis(CE)and to evaluate follow-up and response to treatment in patients affected by CE.METHODS:From January 2000 to December 2010,all patients affected by CE at the Infectious Diseases Units of the University of Catania and of Basilotta Hospital in Nicosia-Enna,were enrolled as participants in the study.Epidemiological,clinical and laboratory data were collected for each patient.Diagnosis of CE was performed using clinical imaging and laboratory parameters.Response to treatment was categorized as follows:"cure"as the disappearance or complete calcification of cyst/s;"improvement"as a reduction in the diameter and/or number of existing cysts;and"impairment"as an increase in the diameter and/or number of existing cyst/s and the onset of relapses(i.e.,the onset of new cyst/s and an increase in the diameter of previously existing cyst/s and/or complications.Immunoglobulin E(IgE)titers and eosinophil percentages were evaluated at diagnosis,at six months after the initiation of treatment and again in the case of relapse.Hyper-eosinophilia was defined as an eosinophil percentage of≥6%.RESULTS:Thirty-two patients were diagnosed with CE in our Unit during the research period,with a malefemale ratio of 2:1.At the time of diagnosis,40%of patients presented a single CE cyst.Sixty percent showed multi-organ involvement.The liver-lung localization ratio was 2:1.Patients below the age of 50 at diagnosis were more likely to have multiple cysts(73.7%vs 35.5%,P<0.05).Regarding treatment,30 patients were treated medically and 16 surgically.Fourteen patients were treated both medically and surgically.Relapses were seen to be less frequent in patients treated with albendazole before and after surgery.Complete cure or an improvement was achieved in 23 patients.Impairment was observed in one patient.Two patients showed no improvement.Relapses were more frequent in those patients treated before 2005.At diagnosis,71%of patients were positive for specific CE IgE,and 56.3%showed an eosinophil percentage of≥6%.Patients who were diagnosed with hyper-eosinophilia developed complications more frequently than the other patients,but did not suffer relapses.CONCLUSION:On the basis of our results,we propose cystic echinococcosis screening for family members of patients,appropriate pre-and post-surgery treatment and the assessment of anti-echinococcus IgE titer or eosinophil percentage as a therapy response marker in settings with limited resources.

The Development of Early Life Microbiota in Human Health and Disease

The colonization of the human microbiota in early life has long-lasting health implications.The status of the initial intestinal microbiota determines human growth and development from infancy to adulthood,and thus represents a crucial window in our long-term development.This review aims to summarize the latest findings on the symbiotic gut microbiota early in life and its vital role in metabolic-,allergic-,and auto-immune-disorder-related diseases,including obesity,diabetes,allergy,autism,inflammatory bowel disease,and stunting.It discusses the development process and various factors shaping the gut micro-biota,as well as the crosstalk between the gut microbiota and the host’s physiological systems(especially intestinal immune development and homeostasis,and the central nervous system in the course of neu-rodevelopment),during the early life establishment of the gut microbiota,in order to decipher the mech-anisms of diseases associated with the intestinal microbiome of early life.In addition,it examines microbiota-targeted therapeutic methods that show promising effects in treating these diseases.The true process of gut microbiome maturation,which depends on genetics,nutrition,and environmental factors,must be scrutinized in order to monitor healthy gut microbiome development and potentially correct unwanted courses by means of intervention via methods such as novel probiotics or fecal microbiota transplantation.

Clinical Investigation: The Presence of Viral Meningitis without Pleocytosis among Pediatric Patients

Background:?Viral meningitis (VM) is mostly common among infants. Its induction by enteroviruses (EVM) is associated with morbidity and is primarily diagnosed by lumbar puncture, which may yield false negatives. We evaluated the frequency of VM by polymerase chain reaction (PCR) among infants with no detected pleocytosis. Furthermore, as literature suggests EVM essentially occurs during summer and fall, we characterized the monthly distribution of EVM cases. Methods:?Infants diagnosed with VM from June 2009 to May 2010 were enrolled in the current prospective study. Following each lumbar puncture, CSF was tested for enteroviruses by PCR. Outcome measures were i) the percentage of EVM cases revealed solely by PCR;and ii) the monthly distribution of EVM cases. Results:Enrolled were 173 VM-diagnosed infants, of whom 75 (43.4%) tested positive in CSF-PCR. Of these, no pleocytosis was indicated in 43 (57%), specifically in 70% and 42% of infants younger than 90 days and older than 1 year, respectively. Furthermore, 119 (69%) infants were admitted during June-November while 54 (31%) during December-May. Conclusions:Current findings stress the high frequency of infants who were tested negative for pleocytosis, yet were diagnosed with VM by PCR. This was especially noticeable among infants younger than 3 months, possibly reflecting their decreased ability to mount a robust inflammatory response to EV infection. CSF-PCR may be warranted in pediatric patients who test negative for pleocytosis. While most EVM cases occurred during the summer and fall, EVM-infants were admitted to the hospital all through the year.

Molecular Evaluation of the Enterotoxigenicity of <i>Clostridium difficile</i>and <i>Clostridium perfringens</i>Swine Isolates by PCR Assays

Clostridium difficile and C. perfringens are enteric pathogens affecting a variety of mammals. This study evaluated the molecular enterotoxigenicity of Clostridium swine isolates by PCRs. One hundred and ten swine faeces were analyzed by culture assay. The faecal samples were from sixty-seven healthy animals and 43 with gastrointestinal tract disease. C. difficile strains were PCR-screened for the presence of tcdA/tcdB and cdtA/cdtB genes. All C. perfringens isolates were tested for the characterization of the toxinotype. Overall, sixty-five swine resulted positive: 38 for C. difficile and 17 for C. perfringens. One sample tested C. perfringens and C. difficile-positive, at the same time: on the whole, 39 C. difficile strains were isolated. Thirty-eight C. difficile isolates (all from healthy animals) resulted tcdA/tcdB and cdtA/cdtB-negative by PCRs and toxins A/B-negative by immunological tests. All C. perfringens strains were type A;eight were also cpb2-positive. In the sample (diarrhoeic), with double infection, C. difficile tested tcdA/tcdB and cdtA/cdtB-positive by PCRs and toxins A/B-positive by immunoassays;C. perfringens resulted cpb2-positive. The molecular genotypeing/toxinotyping should be applied to establish a final diagnosis and to assess properly the full implications and the epidemiological impact of these findings in particular in samples of healthy animals and aid in the development of effective intervention methods for controlling clostridial disease outbreaks.

Happy Hypoxia in COVID-19 Patients at Kinshasa University Hospital (Democratic Republic of the Congo): Frequency and Vital Outcome

Background: Happy hypoxia is a new feature found in COVID-19 patients. It consists of the presence of severe hypoxemia but normal breathing rate. Failure to identify this hypoxia may have negative consequences on the survival of the patient. The objective of the present study was to measure the frequency of patients with happy hypoxia and to evaluate their survival at the Kinshasa University Hospital (KUH). Methods: This was a historical cohort of 141 hospitalized patients with COVID-19 at KUH from March 23 to June 15, 2020. Happy hypoxia was defined as oxygen saturation below 90% without dyspnea. Socio-demographic data, co-morbidities, follow up time of hospitalization and outcomes were studied. Survival was assessed using the Kaplan Meier curve. Results: Out of 141 hospitalized patients with COVID-19, 79 (56%) patients were at the severe or critical stage and 9 (6.4%) had a happy hypoxia on admission. Patients who had happy hypoxia on admission were generally older than 60 years of age (55.6%) (p = 0.023). Comparison of survival curves, based on the presence or absence of happy hypoxia, shows a statistically significant difference (p = 0.001). The presence of happy hypoxia reduces survival. Conclusion: The frequency of happy hypoxia among COVID-19 patients was low. Survival was reduced in patients with happy hypoxia. Prehospital pulse oximetry could serve as an early warning signal for the detection of happy hypoxemia in COVID-19 patients.

肝脏移植术后糖尿病患者肠道微生物组的变化

Post-transplant diabetes mellitus(PTDM)increases the risk of graft failure and death in liver transplant(LT)recipients.Experimental studies have indicated that enteric dysbiosis mediated by immunosuppressive tacrolimus(TAC)could contribute to glucose disorders,but no data on human recipients with PTDM have been reported.Here,by combining high-throughput shotgun metagenomics sequencing and metabolomics profiling,we characterized the intestinal microbiome(IM)in LT recipient cohort with or without PTDM and deciphered the potential relationship among IM,TAC dosage,and diabetes.By comparing with both non-PTDM and classical type 2 diabetes mellitus(T2DM),we identified microbial signatures of PTDM,which was characterized by the enriched Proteobacteria and decreased Bacteroidetes.Additionally,the altered microbes,as well as the microbial metabolomics,correlated with the dosage of TAC.Specifically,the levels of beneficial microbes associated with PTDM were lowered in recipients with the high TAC trough concentrations(>5 ng·mL^(-1))than those with low ones(<5 ng·mL^(-1)),which was accompanied by reduced faecal metabolites involved in the biosynthesis of a-linolenic acid and arachidonic acid-lowering factors of developing T2DM.Moreover,these microbial signatures linked with the extent of glucose disorders in LT recipients.In summary,the faecal microbiome and metabolome differed between PTDM and non-PTDM patients,which were linked with TAC dosage.This study was the first to explore taxonomic alterations and bacterial gene functions to better understand the contribution of the IM to PTDM.

Infectious Microbes&Diseases Contributing to COVID-19 Prevention and Control

Since the start of the outbreak of coronavirus disease 2019(COVID-19)in January 2020,the pandemic has been raging on for 3 years,with a devastating impact on human health,resulting globally in 663,248,631 confirmed infections and 6,709,387 confirmed deaths as of January 19,2023.1 Facing this remarkably fast developing pandemic with limited knowledge on many aspects of the disease,including transmission,effective infection control,morbidity and treatment,researchers and practitioners worldwide have switched their focus to COVID-19–related research and practices.According to incomplete statistics,more than 330,000 COVID-19–related publications have been indexed in PubMed by January 19,2023,2 which carried out comprehensive and multifaceted studies on COVID-19.These research findings have played a key role in controlling the spread of COVID-19,treating severe and/or critical cases,and reducing the morbidity and mortality.

Severe dengue in the intensive care unit

Dengue fever is considered the most prolific vector-borne disease in the world,with its transmission rate increasing more than eight times in the last two decades.While most cases present mild to moderate symptoms,5%of patients can develop severe disease.Although the mechanisms are yet not fully comprehended,immune-mediated activation leading to excessive cytokine expression is suggested as a cause of the two main findings in critical patients:increased vascular permeability that may shock and thrombocytopenia,and coagulopathy that can induce hemorrhage.The risk factors of severe disease include previous infection by a different serotype,specific genotypes associated with more efficient replication,certain genetic polymorphisms,and comorbidities such as diabetes,obesity,and cardiovascular disease.The World Health Organization recommends careful monitoring and prompt hospitalization of patients with warning signs or propensity for severe disease to reduce mortality.This review aims to update the diagnosis and management of patients with severe dengue in the intensive care unit.

Coronavirus disease 2019 in liver transplant patients:Clinical and therapeutic aspects

The coronavirus disease 2019(COVID-19)pandemic has profoundly impacted liver transplant(LT)activity across the world,with notable decreases in the number of donations and procedures in most Western countries,in particular throughout the first wave.The cumulative incidence of COVID-19 in LT recipients(with estimates ranging from 0.34%to 1.56%)appears to be at least comparable to that observed for the general population.Clinical and radiological features at presentation are also similar to non-transplant patients.The risk of death among LT recipients requiring hospital admission is high(from 12% to 19%),although some authors have suggested that overall mortality may be actually lower compared to the general non-transplant population.It is likely that these poor outcomes may be mainly influenced by the older age and higher comorbidity burden of LT recipients,rather than by the transplant status itself.In fact,it has been hypothesized that post-transplant immunosuppression would exert a protective role,with special focus on tacrolimus-containing regimens.There is scarce evidence to guide the optimal management of post-transplant COVID-19 and the use of antiviral or immunomodulatory therapies,although both clinical practice and guidelines support the dose reduction or withdrawal of anti-proliferative agents such as mofetil mycophenolate.Preliminary reports suggest that the antibody response to messenger RNA vaccines is significantly impaired as compared to non-immunocompromised individuals,in line with other transplant populations.Finally,it is foreseeable that the future will be conditioned by the emerging variants of severe acute respiratory syndrome coronavirus 2 with increased transmissibility among LT recipients.

直接面视下短程抗结核化疗影响病人依从性的因素

背景:马来西亚,沙巴,Kota Kinabalu及其周边社区。 目的:了解影响抗结核化疗病人依从性的诸因素,以及他们的结核病知识水平及和DOTS管理的改进意见。 设计:对2000年8月至9月期间到诊所DOTS治疗的合作及不合作病人进行家庭访视。 结果:共访问了63例合作病人和23例不合作病人。对于不合作者,他们去治疗中心的花费(P<0.005)及旅途时间(P<0.005)均比合作者明显要多。交通费常常是不去治疗的主要原因。不合作病人中完成中等教育的多(P<0.05),并且有工作的也多(P<0.01)。更多的不合作者中其家庭成员曾患过本病(P<0.01)。有关结核病知识的得分,两组间无差别;但是,不合作病人大多认为,当症状消失后便可停止治疗(P<0.01)。很多病人(73％)认为,通过提供更多的结核病知识可改善DOTS管理体系。 结论:赴治疗中心的交通费、占用的时间及家庭成员曾患过结核病等因素对沙巴,Kota Kinabalu地区病人的DOTS依从性产生影响。病人愿意获得更多关于结核病的知识。

Identification of Persister Drug Combination Clinafloxacin+Cefuroxime+Gentamicin That Eradicates Persistent Pseudomonas aeruginosa Infection in a Murine Cystic Fibrosis Model

Pseudomonas aeruginosa can cause persistent infections,such as biofilm infections,in cystic fibrosis patients,which are difficult to cure due to non-growing persister bacteria that are not effectively killed by the current treatments.While antibiotic activity against growing P.aeruginosa is well documented,their activity against non-growing stationary phase cultures is less clear.Here,we evaluated six major classes of antibiotics,including cell wall and cell membrane inhibitors,protein synthesis inhibitors,DNA synthesis inhibitors,RNA synthesis inhibitors,sulfa drugs and nitrofurantoin,for their activity against growing and non-growing P.aeruginosa.We foundthat cell wall and cell membrane inhibitors(cefuroxime and colistin),DNA synthesis inhibitors(clinafloxacin)and sulfa drugs(sulfamethoxazole)had good activity against stationary-phase bacteria,while protein synthesis inhibitors(gentamicin),RNA synthesis inhibitor(rifampin)and nitrofurantoin showed relatively poor activity.Clinafloxacin was the only drug able to completely eradicate stationary-phase bacteria within four days.The cefuroxime+gentamicin+clinafloxacin combination was able to kill all bacteria from a biofilm within two days,whereas the clinically used drug combination cefuroxime+gentamicin/colistin only partially killed the biofilmbacteria.In amurine persistent cystic fibrosis lung infectionmodel,only the cefuroxime+gentamicin+clinafloxacin drug combination eradicated all bacteria from the lungs,whereas clinafloxacin alone,cefuroxime+clinafloxacin or the currently recommended drug combination cefuroxime+gentamicin failed to do so.The complete eradication is a property of the clinafloxacin combination,as the otherwise identical levofloxacin combination did not clear the bacterial loads from the lungs.Our findings offer new therapeutic options for more effective treatment of persistent P.aeruginosa infections,with possible implications for treating other persistent infections.

Pneumococcal disease in adult solid organ transplantation recipients

In solid organ transplant(SOT) recipients, Streptococcus pneumoniae can cause substantial morbidityand mortality ranging from non-invasive to invasive diseases, including pneumonia, bacteremia, and meningitis, with a risk of invasive pneumococcal disease 12 times higher than that observed in non-immunocompromised patients. Moreover, pneumococcal infection has been related to graft dysfunction. Several factors have been involved in the risk of pneumococcal disease in SOT recipients, such as type of transplant, time since transplantation, influenza activity, and nasopharyngeal colonization. Pneumococcal vaccination is recommended for all SOT recipients with 23-valent pneumococcal polysaccharides vaccine. Although immunological rate response is appropriate, it is lower than in the rest of the population, decreases with time, and its clinical efficacy is variable. Booster strategy with 7-valent pneumococcal conjugate vaccine has not shown benefit in this population. Despite its relevance, there are few studies focused on invasive pneumococcal disease in SOT recipients. Further studies addressing clinical, microbiological, and epidemiological data of pneumococcal disease in the transplant setting as well as new strategies for improving the protection of SOT recipients are warranted.

利福平耐药性发生过程中,结核分支杆菌DNA指纹图谱无改变

耐药性结核病已成为一个严重的公共卫生问题。利福平耐药性可能是由于分支杆菌RNA聚合酶突变所致。病人获得利福平耐药性的机理可能有三种:(1)由耐药菌引起的感染;(2) 在毒力较强的野生型菌存在的同时,一小群仍处于遏制中的耐药菌的选择;(3)原来感染菌群内的突变。本研究连续收集治疗过程中发生利福平耐药性的2例病人的结核分支杆菌分离菌株。一例病人由于HIV感染而免疫抑制,另一例病人原来分离菌株对异烟肼也耐药。应用DNA指纹技术对分离菌株分型,显示耐药性发生前后的分离菌株之间DNA图谱无差别。这些资料表明,这2例病人获得利福平耐药性是由于上述第三机理。

The Relationship Between the Gut Microbiome and Neurodegen-erative Diseases

Many recent studies have shown that the gut microbiome plays important roles in human physiology and pathology.Also,microbiome-based therapies have been used to improve health status and treat diseases.In addition,aging and neurodegenerative diseases,including Alzheimer’s disease and Parkinson’s disease,have become topics of intense interest in biomedical research.Several researchers have explored the links between these topics to study the potential pathogenic or therapeutic effects of intestinal microbiota in disease.But the exact relationship between neurodegenerative diseases and gut microbiota remains unclear.As technology advances,new techniques for studying the microbiome will be developed and refined,and the relationship between diseases and gut microbiota will be revealed.This article summarizes the known interactions between the gut microbiome and neurodegenerative diseases,highlighting assay techniques for the gut microbiome,and we also discuss the potential therapeutic role of microbiome-based therapies in diseases.

Influence of staff number and internal constellation on surgical site infection in an operating room

Prediction of bacteria-carrying particle （BCP） dispersion and particle distribution released from staffmem- bers in an operating room （OR） is very important for creating and sustaining a safe indoor environment. Postoperative wound infections cause significant morbidity and mortality, and contribute to increased hospitalization time. Increasing the number of personnel within the OR disrupts the ventilation airflow pattern and causes enhanced contamination risk in the area of an open wound. Whether the amount of staffwithin the OR influences the BCP distribution in the surgical zone has rarely been investigated. This study was conducted to explore the influence of the number of personnel in the OR on the airflow field and the BCP distribution. This was performed by applying a numerical calculation to map the airflow field and Lagrangian particle tracking （LPT） for the BCP phase. The results are reported both for active sampling and passive monitoring approaches. Not surprisingly, a growing trend in the BCP concentration （cfu/ms） was observed as the amount of staff in the OR increased. Passive sampling shows unpredictable results due to the sedimentation rate, especially for small particles （5-10 i^m）. Risk factors for surgical site infections （SSls） must be well understood to develop more effective prevention programs.

Role of Akkermansia muciniphila in the development of nonalcoholic fatty liver disease: current knowledge and perspectives

Nonalcoholic fatty liver disease(NAFLD)is a hepatic manifestation of metabolic syndrome and a common cause of liver cirrhosis and cancer.Akkermansia muciniphila(A.muciniphila)is a next-generation probiotic that has been reported to improve metabolic disorders.Emerging evidence indicates the therapeutic potential of A.muciniphila for NAFLD,especially in the inflammatory stage,nonalcoholic steatohepatitis.Here,the current knowledge on the role of A.muciniphila in the progression of NAFLD was summarized.A.muciniphila abundancy is decreased in animals and humans with NAFLD.The recovery of A.muciniphila presented benefits in preventing hepatic fat accumulation and inflammation in NAFLD.The details of how microbes regulate hepatic immunity and lipid accumulation in NAFLD were further discussed.The modulation mechanisms by which A.muciniphila acts to improve hepatic inflammation are mainly attributed to the alleviation of inflammatory cytokines and LPS signals and the downregulation of microbiota-related innate immune cells(such as macrophages).This review provides insights into the roles of A.muciniphila in NAFLD,thereby providing a blueprint to facilitate clinical therapeutic applications.