In addition to being among the major tiggers behind frequent earthquakes,fractures can allow surface water to infiltrate the permeable rocks,entering both shallow and deep aquifers.Occasionally,water penetrates to gre...In addition to being among the major tiggers behind frequent earthquakes,fractures can allow surface water to infiltrate the permeable rocks,entering both shallow and deep aquifers.Occasionally,water penetrates to great depths,heats up,and becomes geothermal water.Fractures similarly allow hydrothermal fluids to dissolve their chemical elements and form a mineral deposit.Given these important roles of fractures,this paper aims to map faults and fractures across the entire Moroccan territory in the form of lineaments extracted from remotely sensed images,and then analyze their spatial distribution using the fractal dimension(FD)approach,and then generate a fractal map of the entire Morocco as a guide for subsurface investigation purposes.It was found that the areas with high fractal dimension(FD˃1),considered potential groundwater recharge areas,essentially the northern Anti Atlas,the southwestern High Atlas,and the Meseta,present spatial conformity with several known mineral deposits,geothermal areas,and the epicenters of many historical earthquakes.This conformity can be a key element in expecting other unexplored mineral deposits,aquifers,or geothermal regions,as well as predicting the areas that may bear earthquake hazards in areas with high FD across the entire Moroccan territory.展开更多
Road construction in Africa is faced with a shortage of quality materials, leading to delays and increased costs. Traditional materials, such as clay soils of the bar soil type, have inadequate properties for pavement...Road construction in Africa is faced with a shortage of quality materials, leading to delays and increased costs. Traditional materials, such as clay soils of the bar soil type, have inadequate properties for pavement sub-base layers, particularly in terms of bearing capacity. This study explores a composite material combining bar soil and bamboo fibers to improve the mechanical performance of bar soil, offering a sustainable and cost-effective solution. The Tori-Bossito bar soil was characterised by particle size analysis, Atterberg limits, Proctor compaction tests and the California Bearing Ratio (CBR). The results show that this material is a class A2 sandy-clay soil with a CBR of 18, which is insufficient for foundation layers requiring a CBR of over 30. To improve its performance, Sèmè-Kpodji bamboo fibers, 30 to 100 microns in diameter and 3 to 5 cm long, were incorporated at rates of 0.9% to 2.7%. The optimum mix, with 2.4% fiber, has a CBR of 35, a dry density of 1.92 t/m3 and a moisture content of 12.4%. This reinforced material is suitable as a base course for low-traffic roadways.展开更多
The fact that Morocco is an agricultural country and the large volume of biodegradable waste produced by the population make composting so important.The degradation of organic matter is facilitated by faunal and flora...The fact that Morocco is an agricultural country and the large volume of biodegradable waste produced by the population make composting so important.The degradation of organic matter is facilitated by faunal and floral macro and micro-organisms that act in different stages of maturation;studies on this fauna are quite rare both nationally and internationally.On a sample of two tons of household waste,we documented invertebrates that colonized compost heaps and then assessed the changes in the structure of the invertebrate population during the different phases.Our study revealed the presence of several zoological groups colonizing the compost heaps during the different composting phases;we noted the presence of:(1)Macroscopic invertebrates,in order of number of individuals:insect larvae,ants,earthworms,sowbugs,spiders,springtails,and millipedes,and(2)Microscopic invertebrates,the most abundant in terms of individuals:mites and nematodes.As for the order of appearance,we observed that insect larvae were the first to colonize the compost heap from the very first days of installation,followed by woodlice observed during the thermophilic phase and disappearing towards the end of the process.Earthworms were observed during the end of the thermophilic phase,while springtails were observed more during the cooling and maturation phases.Our study revealed the presence of a good quality of fauna during the composting process,which are indicators of good compost quality and play a major role in the circulation of nutrients,thus ensuring the provision of essential elements for plant nutrition.展开更多
Trauma is a major health and social problem in the US and China, It constitutes the main cause of death in people aged 45 or under in both countries112]. There is clear evidence from clinical studies that a large perc...Trauma is a major health and social problem in the US and China, It constitutes the main cause of death in people aged 45 or under in both countries112]. There is clear evidence from clinical studies that a large percentage of these deaths are needless and preventable if better treatment and prevention programs are available12-3].展开更多
Globally, over 300 million people are living with viral he-patitis with approximately 1.3 million deaths per year. In 2016, World Health Assembly adopted the Global Health Sector Strategy on viral hepatitis to elimina...Globally, over 300 million people are living with viral he-patitis with approximately 1.3 million deaths per year. In 2016, World Health Assembly adopted the Global Health Sector Strategy on viral hepatitis to eliminate hepatitis by 2030. Different World Health Organization member countries are working on hepatitis control strategies to achieve hepatitis elimination. So far, only 12 countries are on track to achieve hepatitis elimination targets. The aim of the study was to give an update about the progress and challenges to achieving hepatitis elimination by 2030. According to the latest data, 87% of infants had received the three doses of hepatitis B virus （HBV） vaccination in the frst year of their life and 46% of infants had received a timely birth dose of HBV vaccination.There is a strong need to improve blood and injection safety. Rates of hepatitis B and C diagnosis are very low and only 11% of hepatitis B and C cases are diagnosed. There is a dire need to speed up hepatitis diagnosis and find the missing millions of people living with viral hepatitis. Up to 2016, only 3 million hepatitis C cases have been treated. Pricing of hepatitis C virus drugs is also reduced in many countries. The major hurdle to ach-ieve hepatitis elimination is lack of finances to support hepatitis programs. None of the major global donors are committed to invest in the fght against hepatitis. It will be very diffcult for the low and middle-income countries to fund their hepatitis control program. Hepatitis elimination needs strong fnancial and political commitment, support from civil societies, and support from pharmaceutical and medical companies around the globe.展开更多
In 2016,the World Health Assembly adopted a Global Health Sector Strategy on viral hepatitis,with targets set for the years 2020 and 2030 to achieve hepatitis elimination.The main target of hepatitis elimination strat...In 2016,the World Health Assembly adopted a Global Health Sector Strategy on viral hepatitis,with targets set for the years 2020 and 2030 to achieve hepatitis elimination.The main target of hepatitis elimination strategy is to reduce the incidence of hepatitis B virus(HBV)and hepatitis C virus(HCV)by 90%and mortality by 65%in 2030.In last 5 years,the number of people receiving HCV treatment has increased from 1 million to 9.4 million;however,this number is far from the 2030 target of 40 million people receiving HCV treatment.HBV and HCV incidence rates are down from 1.4 million to 1.1 million annual deaths but this is far from the 2030 target of<0.5 million deaths.The coronavirus disease 2019 pandemic has severely affected the efforts in the fight against hepatitis.No major donor has committed to investing in the fight against hepatitis.Time is running out.There is a need to speed up efforts in the fight against hepatitis to achieve hepatitis elimination by 2030.展开更多
Chemical composition of the bark extracts of Coula edulis was investigated to find potential antioxidant,anti-termite and antifungal compounds which can find useful applications in the fields of food,nutraceuticals,co...Chemical composition of the bark extracts of Coula edulis was investigated to find potential antioxidant,anti-termite and antifungal compounds which can find useful applications in the fields of food,nutraceuticals,cosmetics or agrochemical.Phytochemical screening revealed the presence of several groups of active molecules such as alkaloids,polyphenols,flavonoids,saponins and sterols and/or terpenes in the different extracts.Total phenols,condensed tannins and flavonoids contents corroborated phytochemical screening.Gas chromatographymass spectrometry(GC-MS)analysis revealed compounds in dichloromethane extract different from those obtained with all the other solvents.Hexadecanoic and trans-9-octadecenoic acids,as well as stigmasterol andβ-sitosterol have been identified as the major compounds in the dichloromethane extract.Extracts obtained with acetone and toluene/ethanol mixture(2/1,v/v)indicated the presence of few amounts of fatty acids and sugars,catechin in small amount and huge amounts of phenolic acids like gallic and ellagic acids.The radical 2,2-diphenyl-1-picrylhydrazyle(DPPH)and the cationic radical 2,2’-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS+)were used for evaluation of antioxidant properties of the different extracts.The dichloromethane extracts had a very low antioxidant activity,while acetone and toluene/ethanol extracts presented EC50 values similar to those of catechin and BHT used as reference antioxidant compounds.Effect of the different extracts of the bark of C.edulis on fungal growth inhibition indicated better inhibition of the mycelium growth of brown rot fungi compared to white rot fungi.Low anti-termite activities were recorded with the aqueous extracts,while stronger activities were recorded with dichloromethane,acetone and toluene/ethanol extracts.展开更多
To identify environmental risk factors associated with the development of Crohn’s disease (CD) in order to re-assess the hygiene hypothesis. METHODSA hospital-based, case-control study was carried out with CD patient...To identify environmental risk factors associated with the development of Crohn’s disease (CD) in order to re-assess the hygiene hypothesis. METHODSA hospital-based, case-control study was carried out with CD patients (n = 145) and controls (n = 163) representing a socioeconomically diverse statewide catchment area in Brazil. Controls were recruited from caregivers of patients seen in different outpatient clinics at the same hospital. A multi-item survey with 94 questions regarding family history of CD, perinatal and childhood circumstances, living conditions, tobacco use and familial socioeconomic status was carried out by interviewers. RESULTSOn the univariate analysis, predictive variables for CD included being male, under age of 40, a high education level, urban dweller, smaller family size, exposure to enteric pathogens and user of treated water (P < 0.005). On the multivariate analysis, variables significantly associated with CD were male gender (OR = 2.09), under age 40 (OR = 3.10), white (OR = 2.32), from a small family in childhood (OR = 2.34) and adulthood (OR = 3.02), absence of viral infections in childhood (OR = 2.23), exposure to enteric pathogens (OR = 2.41), having had an appendectomy (OR = 2.47) and prior or current smoker (OR = 2.83/1.12). CONCLUSIONMost variables supporting the “hygiene hypothesis” are associated with the development of CD but are not independent predictors of the diagnosis.展开更多
AIM To address the hypothesis that young, gonad-intact female mice have improved long-term recovery associated with decreased neuroinflammation compared to male mice.METHODS Eight to ten week-old male, female, and ova...AIM To address the hypothesis that young, gonad-intact female mice have improved long-term recovery associated with decreased neuroinflammation compared to male mice.METHODS Eight to ten week-old male, female, and ovariectomized(OVX) mice underwent closed cranial impact. Gonadintact female mice were injured only in estrus state. After injury, between group differences were assessed using complementary immunohistochemical staining for microglial cells at 1 h, m RNA polymerase chain reaction for inflammatory markers at 1 h after injury, Rotarod over days 1-7, and water maze on days 28-31 after injury. RESULTS Male mice had a greater area of injury(P = 0.0063), F4/80-positive cells(P = 0.032), and up regulation of inflammatory genes compared to female mice. Male and OVX mice had higher mortality after injury when compared to female mice(P = 0.043). No groupdifferences were demonstrated in Rotarod latencies(P = 0.62). OVX mice demonstrated decreased water maze latencies compared to other groups(P = 0.049). CONCLUSION Differences in mortality, long-term neurological recovery, and markers of neuroinflammation exist between female and male mice after moderate traumatic brain injury(MTBI). Unexpectedly, OVX mice have decreased long term neurological function after MTBI when compared to gonad intact male and female mice. As such, it can be concluded that the presence of female gonadal hormones may influence behavioural outcomes after MTBI, though mechanisms involved are unclear.展开更多
In this work,a one-pot strategy is presented to directly synthesize amorphous Fe_(x)Ni_(y) hydroxide nanoclusters(denoted as ANC-Fe_(x)Ni_(y),<2 nm)with oxygen vacancies induced by ionic liquids.The ANC-Fe_(x)Ni_(y...In this work,a one-pot strategy is presented to directly synthesize amorphous Fe_(x)Ni_(y) hydroxide nanoclusters(denoted as ANC-Fe_(x)Ni_(y),<2 nm)with oxygen vacancies induced by ionic liquids.The ANC-Fe_(x)Ni_(y) catalyst presents abundant catalytic sites and high intrinsic conductivity.As such,the optimized ANC-Fe_(1)Ni_(2) exhibits high activity in oxygen evolution reaction(OER)with a Tafel slope of 39 m V dec^(–1) and an overpotential of 266 m V at 10 m A cm^(-2).Notably,the optimized ANC-Fe_(1)Ni_(2) shows an extraordinarily large mass activity of 3028 Ag_(FeNi)^(–1) at the overpotential of 300 m V,which is~24-fold of commercial RuO_(2) catalyst.The superior activity of these Fe_(x)Ni_(y) hydroxide nanoclusters is ascribed to(i)the amorphous and distorted structure with abundant oxygen vacancies,and(ii)enhanced active site density by downsizing the ANC-FexNiyclusters.This strategy provides a novel route for enhancing OER electrocatalytic performance and highly encouraging for the future application of amorphous metal hydroxides in catalysis.展开更多
BACKGROUND The etiology of inflammatory bowel disease(IBD)is unknown,but it is believed to be multifactorial.The hygiene hypothesis proposes that better hygiene conditions would lead to less infectious disease during ...BACKGROUND The etiology of inflammatory bowel disease(IBD)is unknown,but it is believed to be multifactorial.The hygiene hypothesis proposes that better hygiene conditions would lead to less infectious disease during childhood and favor the development of immune-mediated diseases.AIM To test the hygiene hypothesis in IBD by assessing the environmental risk factors associated with IBD development in different regions of Brazil with diverse socioeconomic development indices.METHODS A multicenter case-control study was carried out with 548 Crohn’s disease(CD)and 492 ulcerative colitis(UC)outpatients and 416 healthy controls,from six IBD centers within different Brazilian states at diverse socioeconomic development stages.A semi-structured questionnaire with 87 socioeconomic and environmental questions was applied.Logistic regression model was created to assess the odds ratio(OR)with P value and 95%confidence intervals(CI).RESULTS Predictive variables for both diseases(CD and UC)were women[odd ratios(OR)=1.31;OR=1.69],low monthly family income(OR=1.78;OR=1.57),lower number of cohabitants(OR=1.70;OR=1.60),absence of vaccination(OR=3.11;OR=2.51),previous history of bowel infections(OR=1.78;OR=1.49),and family history of IBD(OR=5.26;OR=3.33).Associated risk factors for CD were age(18-39 years)(OR=1.73),higher educational level(OR=2.22),absence of infectious childhood diseases(OR=1.99).The UC predictive variables were living in an urban area(OR=1.62),inadequate living conditions(OR=1.48)and former smokers(OR=3.36).Appendectomy was a risk factor for CD(OR=1.58)with inverse association with UC(OR=4.79).Consumption of treated and untreated water was associated with risk of CD(OR=1.38)and UC(OR=1.53),respectively.CONCLUSION This is the first examining environmental exposures as risk factors for inflammatory bowel disease in Brazil.Most of the variables associated with disease risk support the role of the hygiene hypothesis in IBD development.展开更多
Pneumonia, a respiratory infection induces acute or chronic inflammation, characterized by increased activity of lymphocytes and neutrophils, thus generating oxygen-free radicals that decrease the endogenous antioxida...Pneumonia, a respiratory infection induces acute or chronic inflammation, characterized by increased activity of lymphocytes and neutrophils, thus generating oxygen-free radicals that decrease the endogenous antioxidants defence system. The aim of this experimental study focused on the capacity of nontoxic aqueous, hydroethanolic and ethanolic extracts of Greenwayodendron suaveolens (Engl. & Diels) Verdc. subsp. suaveolens to regulate free reactive species and protein inflammation generated by infectious disease. The phytochemical screenings of G. suaveolens extracts were carried out according to precipitation and colorimetric methods. The total antioxidant and flavonoid contents were determined by the Folin-Ciocalteu and Aluminium Chloride ethanolic methods. The efficiency of G. suaveolens extracts on free radicals was evaluated using DPPH<sup>•</sup>, ABTS<sup>+•</sup>, and FRAP methods. The anti-inflammatory properties of extracts were evaluated according to in vitro protein (BSA) denaturation, Proteinase Inhibitory Action, and Red Blood Cell Membrane stabilization assays. The G. suaveolens aqueous, hydroethanolic and ethanolic extracts were used for the acute toxicity assessment according to the OECD protocol. The obtained results showed the presence of flavonoids, phenols, polyphenols, tannins, anthocyanins, alkaloids, terpenoids, and sterols as secondary metabolites families in G. suaveolens extracts. The highest contents of total antioxidants and flavonoids were highlighted in the hydroethanolic extract. However, it’s the G. suaveolens aqueous extract that showed the best free radical DPPH<sup>•</sup> and ABTS<sup>+•</sup> scavenging activities (SC<sub>50</sub>) of 11.06 μg/mL and 15.16 μg/mL respectively. The highest ferric-reducing activity was found in G. suaveolens ethanolic extract with 866.23 μg EGA/mg of dry weight. The hydroethanolic extract has shown a high anti-inflammatory activity through BSA denaturation and erythrocyte membrane haemolysis with inhibitory concentrations 50 (IC<sub>50</sub>) of 48.63 and 59.22 μg/mL respectively. In contrast, proteinase inhibitory activity revealed a better potential of IC<sub>50</sub> (34.19 μg/mL) for the ethanolic extract. In oral acute toxicity, all treated groups revealed neither mortality nor any significant alteration in behaviour and locomotion. The lethal dose 50 (LD<sub>50</sub>) of G. suaveolens extracts was >5000 mg/kg. These results suggest that G. suaveolens stem-barks extracts may serve as therapeutic sources to prevent inflammation induced by oxidative stress, an important feature of infectious diseases.展开更多
This work focuses on the design of a new type of eco-material based on Typha“Domingensis”and clay from the south of the Republic of Benin through various dosages.Three particle size classes of typha shavings were se...This work focuses on the design of a new type of eco-material based on Typha“Domingensis”and clay from the south of the Republic of Benin through various dosages.Three particle size classes of typha shavings were selected to be mixed with two types of clayin order to make parallelepiped shaped samples ready for experimentation.The massive use of these briquettes thus obtained,in the construction of habitats,would not only contribute to reducing the energy consumption inside the dwellings but also would limit the invasion of the waterways of Benin,which would facilitate navigation,fishing and river sanitation activities.In addition,this biosourced,low-polluting material would contribute to improving the energy transition by integrating it into rehabilitation of buildings.展开更多
Objective:This study investigates the efficacy and mechanisms of Qingjie Fuzheng Granules(QFG)in inhibiting colitis-associated colorectal cancer(CAC)development via RNA sequencing(RNA-seq)and16S ribosomal RNA(rRNA)cor...Objective:This study investigates the efficacy and mechanisms of Qingjie Fuzheng Granules(QFG)in inhibiting colitis-associated colorectal cancer(CAC)development via RNA sequencing(RNA-seq)and16S ribosomal RNA(rRNA)correlation analysis.Methods:CAC was induced in BALB/c mice using azoxymethane(AOM)and dextran sulfate sodium(DSS),and QFG was administered orally to the treatment group.The effects of QFG on CAC were evaluated using disease index,histology,and serum T-cell ratios.RNA-seq and 16S rRNA analysis assessed the transcriptome and microbiome change.Key pharmacodynamic pathways were identified by integrating these data and confirmed via Western blotting and immunofluorescence.The link between microbiota and CACrelated markers was explored using linear discriminant analysis effect size and Spearman correlation analysis.Results:Long-term treatment with QFG prevented AOM/DSS-induced CAC formation,reduced levels of interleukin(IL)-1βtumor necrosis factor-alpha(TNF-α),IL-6,and interferon y(IFN-y),and increased CD3^(+)and CD4^(+)/CD8^(+)T cells ratio,without causing hepatic or renal toxicity.A 16S rRNA analysis revealed that QFG rebalanced the Firmicutes/Bacteroidetes ratio and mitigated AOM/DSS-induced microbiota disturbances.Transcriptomics and Western blotting analysis identified the nucleotide-binding oligomerization domain-containing protein 2(NOD2)/nuclear factor kappa-B(NF-κB)pathway as key for QFG's treatment against CAC.Furthermore,QFG decreased the abundance of Bacilli,Bacillales,Staphylococcaceae,Staphylococcus,Lactobacillales,Aerococcus,Alloprevotella,and Akkermansia,while increasing Clostridiales,Lachnospiraceae,LachnospiraceaeNK4A136group,Ruminococcaceae,and Muribaculaceae,which were highly correlated with CAC-related markers or NOD2/NF-kB pathway.Conclusion:By mapping the relationships between CAC,immune responses,microbiota,and key pathways,this study clarifies the mechanism of QFG in inhibiting CAC,highlighting its potential for clinical use as preventive therapy.展开更多
Background Spinal cord injury （SCI） is a complex trauma that consists of multiple pathological mechanisms involving cytotoxic, oxidation stress and immune-endocrine. This study aimed to establish plasma metabonomics...Background Spinal cord injury （SCI） is a complex trauma that consists of multiple pathological mechanisms involving cytotoxic, oxidation stress and immune-endocrine. This study aimed to establish plasma metabonomics fingerprinting atlas for SCI using 1H nuclear magnetic resonance （NMR） based metabonomics methodology and principal component analysis techniques.Methods Nine Sprague-Dawley （SD） male rats were randomly divided into SCI, normal and sham-operation control groups. Plasma samples were collected for 1H NMR spectroscopy 3 days after operation. The NMR data were analyzed using principal component analysis technique with Matlab software.Results Metabonomics analysis was able to distinguish the three groups （SCI, normal control, sham-operation）. The fingerprinting atlas indicated that, compared with those without SCI, the SCI group demonstrated the following characteristics with regard to second principal component： it is made up of fatty acids, myc-inositol, arginine, very low-density lipoprotein （VLDL）, low-density lipoprotein （LDL）, triglyceride （TG）, glucose, and 3-methyl-histamine.Conclusions The data indicated that SCI results in several significant changes in plasma metabolism early on and that a metabonomics approach based on 1H NMR spectroscopy can provide a metabolic profile comprising several metabolite classes and allow for relative quantification of such changes. The results also provided support for further development and application of metabonomics technologies for studying SCI and for the utilization of multivariate models for classifying the extent of trauma within an individual.展开更多
Small ubiquitin-like modifier(SUMO)conjugation(SUMOylation)is a post-translational protein modification that modulates almost all major cellular processes,and has been implicated in many human diseases.A growing body ...Small ubiquitin-like modifier(SUMO)conjugation(SUMOylation)is a post-translational protein modification that modulates almost all major cellular processes,and has been implicated in many human diseases.A growing body of evidence from in vitro and in vivo studies demonstrates that increasing global levels of SUMO conjugated proteins(global SUMOylation)protects cells against ischaemia-induced damage,while suppressing global SUMOylation promotes cell injury after ischaemia.Indeed,SUMOylation has emerged as a potential therapeutic target for neuroprotection in brain ischaemia,including global brain ischaemia and focal brain ischaemia(ischaemic stroke).Here,we summarise findings on the role of SUMOylation in human diseases,brain ischaemia in particular,and review recent developments in drug discovery targeting SUMOylation with a major focus on its neuroprotective applications.展开更多
Background:We aimed to systematically review the efficacy of mannitol(MTL)on patients with acute severe traumatic brain injury(TBI).Methods:Databases such as PubMed(US National Library of Medicine),CENTRAL(The Cochran...Background:We aimed to systematically review the efficacy of mannitol(MTL)on patients with acute severe traumatic brain injury(TBI).Methods:Databases such as PubMed(US National Library of Medicine),CENTRAL(The Cochrane Library 2014,Issue 3),ISI(Web of Science:Science Citation Index Expanded),Chinese Biomedicine Database(CBM),and China Knowledge Resource Integrated Database(CNKI)have been searched for relevant studies published between 1 January 2003 and 1 October 2014.We have established inclusion and exclusion criteria to identify RCTs,which were suitable to be enrolled in the systematic review.The comparison group could be hypertonic saline(HS),hydroxyethyl starch,or others.The quality assessment was based on the Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.1 and modified Jadad score scale.The major outcome was mortality,followed by the secondary outcomes such as neurological outcome,days on intensive care unit(ICU),and ventilator day.In addition,intracranial pressure(ICP),cerebral perfusion pressure(CPP),and mean arterial pressure(MAP)were used as the surrogate endpoints.Data synthesis and meta-analysis was conducted by using R(version 3.7-0.).Results:When 176 potential relevant literatures and abstracts have been screened,four RCTs met all the inclusion criteria and were enrolled for the meta-analysis.Amongst all the enrolled studies,two trials have provided the primary outcome data.There was no heterogeneity between two studies(I2=0%)and a fixed model was used for meta-analysis(n=53),pooled result indicated that the mortality was similar in mannitol intervention and control treatment,OR=0.80,95%CI[0.27,2.37],P=0.38.We found that both mannitol and HS were efficient in decreasing the ICP.Furthermore,the effect of the HS on the ICP appeared to be more effective in the patients with diffuse brain injuries than mannitol did.Conclusions:As a conclusion,the mannitol therapy cannot reduce the mortality risk of acute severe traumatic brain injury.Current evidence does not support the mannitol as an effective treatment of acute severe traumatic brain injury.The well-designed randomized controlled trials are in urgent need to demonstrate the adoption of mannitol to acute severe traumatic brain injury.展开更多
Inborn errors of the signal transducer and activator of transcription 1(STAT1)result in four types of immunodeficiency disease with varying degrees of impaired STAT1 function:autosomal recessive(AR)complete STAT1 defi...Inborn errors of the signal transducer and activator of transcription 1(STAT1)result in four types of immunodeficiency disease with varying degrees of impaired STAT1 function:autosomal recessive(AR)complete STAT1 deficiency,AR partial STAT1 deficiency,autosomal dominant(AD)STAT1 deficiency,and AD STAT1 gain-of-function(STAT1-GOF).Of which,the STAT1-GOF mutations promote a clinical syndrome of immune dysregulation characterized by recurrent infections,especially chronic mucocutaneous candidiasis(CMC)and Talaromyces marneffei infection and predisposition to humoral autoimmunity.STAT1-GOF mutations lead to enhanced phosphorylation of STAT1(pSTAT1),delayed dephosphorylation,and impaired nuclear dephosphorylation.As a result,the development of T helper(Th)17 cells is impaired,limiting the production of interleukin(IL)-17,which plays an important role in antifungal immunity.Additionally,mutations can also cause a decrease in the proportion of CD4^(+),CD8^(+),and natural killer(NK)cells.Recent research demonstrated that in the absence of overt infection,STAT-GOF mice can disrupt naïve CD4^(+)T cell homeostasis and promote expansion and differentiation of abnormal T-follicular helper/T-helper 1-like(Tfh/Th1-like)T cells and germinal center-like(GC-like)B cells,and thus reminds us of the complex molecular mechanism of autoimmune disease with/without fungal infection,which may further involve specific clinical treatment including antifungal and anti-autoimmunity therapies.In addition,sex and location of mutation were also associated with the clinical phenotype.Individuals with DNA binding domain(DBD)mutations had a higher prevalence of autoimmunity and aberrant B cell activation.Disrupted CD4^(+)T cell homeostasis occurred sooner and more robustly in females,highlighting the importance of specific treatment to normalize STAT1 expression and restore immune tolerance in patients with STAT1-GOF syndrome.Herein,we provide a comprehensive review of STAT1-GOF aiming to further clarify the regulatory mechanism of cellular and humoral immune deficiency in patients with fungal infection with or without autoimmunity.展开更多
文摘In addition to being among the major tiggers behind frequent earthquakes,fractures can allow surface water to infiltrate the permeable rocks,entering both shallow and deep aquifers.Occasionally,water penetrates to great depths,heats up,and becomes geothermal water.Fractures similarly allow hydrothermal fluids to dissolve their chemical elements and form a mineral deposit.Given these important roles of fractures,this paper aims to map faults and fractures across the entire Moroccan territory in the form of lineaments extracted from remotely sensed images,and then analyze their spatial distribution using the fractal dimension(FD)approach,and then generate a fractal map of the entire Morocco as a guide for subsurface investigation purposes.It was found that the areas with high fractal dimension(FD˃1),considered potential groundwater recharge areas,essentially the northern Anti Atlas,the southwestern High Atlas,and the Meseta,present spatial conformity with several known mineral deposits,geothermal areas,and the epicenters of many historical earthquakes.This conformity can be a key element in expecting other unexplored mineral deposits,aquifers,or geothermal regions,as well as predicting the areas that may bear earthquake hazards in areas with high FD across the entire Moroccan territory.
文摘Road construction in Africa is faced with a shortage of quality materials, leading to delays and increased costs. Traditional materials, such as clay soils of the bar soil type, have inadequate properties for pavement sub-base layers, particularly in terms of bearing capacity. This study explores a composite material combining bar soil and bamboo fibers to improve the mechanical performance of bar soil, offering a sustainable and cost-effective solution. The Tori-Bossito bar soil was characterised by particle size analysis, Atterberg limits, Proctor compaction tests and the California Bearing Ratio (CBR). The results show that this material is a class A2 sandy-clay soil with a CBR of 18, which is insufficient for foundation layers requiring a CBR of over 30. To improve its performance, Sèmè-Kpodji bamboo fibers, 30 to 100 microns in diameter and 3 to 5 cm long, were incorporated at rates of 0.9% to 2.7%. The optimum mix, with 2.4% fiber, has a CBR of 35, a dry density of 1.92 t/m3 and a moisture content of 12.4%. This reinforced material is suitable as a base course for low-traffic roadways.
文摘The fact that Morocco is an agricultural country and the large volume of biodegradable waste produced by the population make composting so important.The degradation of organic matter is facilitated by faunal and floral macro and micro-organisms that act in different stages of maturation;studies on this fauna are quite rare both nationally and internationally.On a sample of two tons of household waste,we documented invertebrates that colonized compost heaps and then assessed the changes in the structure of the invertebrate population during the different phases.Our study revealed the presence of several zoological groups colonizing the compost heaps during the different composting phases;we noted the presence of:(1)Macroscopic invertebrates,in order of number of individuals:insect larvae,ants,earthworms,sowbugs,spiders,springtails,and millipedes,and(2)Microscopic invertebrates,the most abundant in terms of individuals:mites and nematodes.As for the order of appearance,we observed that insect larvae were the first to colonize the compost heap from the very first days of installation,followed by woodlice observed during the thermophilic phase and disappearing towards the end of the process.Earthworms were observed during the end of the thermophilic phase,while springtails were observed more during the cooling and maturation phases.Our study revealed the presence of a good quality of fauna during the composting process,which are indicators of good compost quality and play a major role in the circulation of nutrients,thus ensuring the provision of essential elements for plant nutrition.
基金supported by grants from Sichuan Department of Science and Technology(No.2011SZ0139,2011SZ0336,2012SZ0181)Chengdu Municipality of Bureau of Science and Technology(No.11PPYB099SF-289,12PPYB181SF-002)grants from Sichuan Department of Health(No.100552 and No.100553)
文摘Trauma is a major health and social problem in the US and China, It constitutes the main cause of death in people aged 45 or under in both countries112]. There is clear evidence from clinical studies that a large percentage of these deaths are needless and preventable if better treatment and prevention programs are available12-3].
文摘Globally, over 300 million people are living with viral he-patitis with approximately 1.3 million deaths per year. In 2016, World Health Assembly adopted the Global Health Sector Strategy on viral hepatitis to eliminate hepatitis by 2030. Different World Health Organization member countries are working on hepatitis control strategies to achieve hepatitis elimination. So far, only 12 countries are on track to achieve hepatitis elimination targets. The aim of the study was to give an update about the progress and challenges to achieving hepatitis elimination by 2030. According to the latest data, 87% of infants had received the three doses of hepatitis B virus （HBV） vaccination in the frst year of their life and 46% of infants had received a timely birth dose of HBV vaccination.There is a strong need to improve blood and injection safety. Rates of hepatitis B and C diagnosis are very low and only 11% of hepatitis B and C cases are diagnosed. There is a dire need to speed up hepatitis diagnosis and find the missing millions of people living with viral hepatitis. Up to 2016, only 3 million hepatitis C cases have been treated. Pricing of hepatitis C virus drugs is also reduced in many countries. The major hurdle to ach-ieve hepatitis elimination is lack of finances to support hepatitis programs. None of the major global donors are committed to invest in the fght against hepatitis. It will be very diffcult for the low and middle-income countries to fund their hepatitis control program. Hepatitis elimination needs strong fnancial and political commitment, support from civil societies, and support from pharmaceutical and medical companies around the globe.
文摘In 2016,the World Health Assembly adopted a Global Health Sector Strategy on viral hepatitis,with targets set for the years 2020 and 2030 to achieve hepatitis elimination.The main target of hepatitis elimination strategy is to reduce the incidence of hepatitis B virus(HBV)and hepatitis C virus(HCV)by 90%and mortality by 65%in 2030.In last 5 years,the number of people receiving HCV treatment has increased from 1 million to 9.4 million;however,this number is far from the 2030 target of 40 million people receiving HCV treatment.HBV and HCV incidence rates are down from 1.4 million to 1.1 million annual deaths but this is far from the 2030 target of<0.5 million deaths.The coronavirus disease 2019 pandemic has severely affected the efforts in the fight against hepatitis.No major donor has committed to investing in the fight against hepatitis.Time is running out.There is a need to speed up efforts in the fight against hepatitis to achieve hepatitis elimination by 2030.
文摘Chemical composition of the bark extracts of Coula edulis was investigated to find potential antioxidant,anti-termite and antifungal compounds which can find useful applications in the fields of food,nutraceuticals,cosmetics or agrochemical.Phytochemical screening revealed the presence of several groups of active molecules such as alkaloids,polyphenols,flavonoids,saponins and sterols and/or terpenes in the different extracts.Total phenols,condensed tannins and flavonoids contents corroborated phytochemical screening.Gas chromatographymass spectrometry(GC-MS)analysis revealed compounds in dichloromethane extract different from those obtained with all the other solvents.Hexadecanoic and trans-9-octadecenoic acids,as well as stigmasterol andβ-sitosterol have been identified as the major compounds in the dichloromethane extract.Extracts obtained with acetone and toluene/ethanol mixture(2/1,v/v)indicated the presence of few amounts of fatty acids and sugars,catechin in small amount and huge amounts of phenolic acids like gallic and ellagic acids.The radical 2,2-diphenyl-1-picrylhydrazyle(DPPH)and the cationic radical 2,2’-azinobis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS+)were used for evaluation of antioxidant properties of the different extracts.The dichloromethane extracts had a very low antioxidant activity,while acetone and toluene/ethanol extracts presented EC50 values similar to those of catechin and BHT used as reference antioxidant compounds.Effect of the different extracts of the bark of C.edulis on fungal growth inhibition indicated better inhibition of the mycelium growth of brown rot fungi compared to white rot fungi.Low anti-termite activities were recorded with the aqueous extracts,while stronger activities were recorded with dichloromethane,acetone and toluene/ethanol extracts.
文摘To identify environmental risk factors associated with the development of Crohn’s disease (CD) in order to re-assess the hygiene hypothesis. METHODSA hospital-based, case-control study was carried out with CD patients (n = 145) and controls (n = 163) representing a socioeconomically diverse statewide catchment area in Brazil. Controls were recruited from caregivers of patients seen in different outpatient clinics at the same hospital. A multi-item survey with 94 questions regarding family history of CD, perinatal and childhood circumstances, living conditions, tobacco use and familial socioeconomic status was carried out by interviewers. RESULTSOn the univariate analysis, predictive variables for CD included being male, under age of 40, a high education level, urban dweller, smaller family size, exposure to enteric pathogens and user of treated water (P < 0.005). On the multivariate analysis, variables significantly associated with CD were male gender (OR = 2.09), under age 40 (OR = 3.10), white (OR = 2.32), from a small family in childhood (OR = 2.34) and adulthood (OR = 3.02), absence of viral infections in childhood (OR = 2.23), exposure to enteric pathogens (OR = 2.41), having had an appendectomy (OR = 2.47) and prior or current smoker (OR = 2.83/1.12). CONCLUSIONMost variables supporting the “hygiene hypothesis” are associated with the development of CD but are not independent predictors of the diagnosis.
文摘AIM To address the hypothesis that young, gonad-intact female mice have improved long-term recovery associated with decreased neuroinflammation compared to male mice.METHODS Eight to ten week-old male, female, and ovariectomized(OVX) mice underwent closed cranial impact. Gonadintact female mice were injured only in estrus state. After injury, between group differences were assessed using complementary immunohistochemical staining for microglial cells at 1 h, m RNA polymerase chain reaction for inflammatory markers at 1 h after injury, Rotarod over days 1-7, and water maze on days 28-31 after injury. RESULTS Male mice had a greater area of injury(P = 0.0063), F4/80-positive cells(P = 0.032), and up regulation of inflammatory genes compared to female mice. Male and OVX mice had higher mortality after injury when compared to female mice(P = 0.043). No groupdifferences were demonstrated in Rotarod latencies(P = 0.62). OVX mice demonstrated decreased water maze latencies compared to other groups(P = 0.049). CONCLUSION Differences in mortality, long-term neurological recovery, and markers of neuroinflammation exist between female and male mice after moderate traumatic brain injury(MTBI). Unexpectedly, OVX mice have decreased long term neurological function after MTBI when compared to gonad intact male and female mice. As such, it can be concluded that the presence of female gonadal hormones may influence behavioural outcomes after MTBI, though mechanisms involved are unclear.
基金the financial support by the Natural Science Foundation of China(22172167)the Senior Talent Startup Funds of Jiangsu University(4111310024)。
文摘In this work,a one-pot strategy is presented to directly synthesize amorphous Fe_(x)Ni_(y) hydroxide nanoclusters(denoted as ANC-Fe_(x)Ni_(y),<2 nm)with oxygen vacancies induced by ionic liquids.The ANC-Fe_(x)Ni_(y) catalyst presents abundant catalytic sites and high intrinsic conductivity.As such,the optimized ANC-Fe_(1)Ni_(2) exhibits high activity in oxygen evolution reaction(OER)with a Tafel slope of 39 m V dec^(–1) and an overpotential of 266 m V at 10 m A cm^(-2).Notably,the optimized ANC-Fe_(1)Ni_(2) shows an extraordinarily large mass activity of 3028 Ag_(FeNi)^(–1) at the overpotential of 300 m V,which is~24-fold of commercial RuO_(2) catalyst.The superior activity of these Fe_(x)Ni_(y) hydroxide nanoclusters is ascribed to(i)the amorphous and distorted structure with abundant oxygen vacancies,and(ii)enhanced active site density by downsizing the ANC-FexNiyclusters.This strategy provides a novel route for enhancing OER electrocatalytic performance and highly encouraging for the future application of amorphous metal hydroxides in catalysis.
基金Supported by Carlos Chagas Filho Rio de Janeiro State Research Foundation(Faperj),No.100.044/2011.
文摘BACKGROUND The etiology of inflammatory bowel disease(IBD)is unknown,but it is believed to be multifactorial.The hygiene hypothesis proposes that better hygiene conditions would lead to less infectious disease during childhood and favor the development of immune-mediated diseases.AIM To test the hygiene hypothesis in IBD by assessing the environmental risk factors associated with IBD development in different regions of Brazil with diverse socioeconomic development indices.METHODS A multicenter case-control study was carried out with 548 Crohn’s disease(CD)and 492 ulcerative colitis(UC)outpatients and 416 healthy controls,from six IBD centers within different Brazilian states at diverse socioeconomic development stages.A semi-structured questionnaire with 87 socioeconomic and environmental questions was applied.Logistic regression model was created to assess the odds ratio(OR)with P value and 95%confidence intervals(CI).RESULTS Predictive variables for both diseases(CD and UC)were women[odd ratios(OR)=1.31;OR=1.69],low monthly family income(OR=1.78;OR=1.57),lower number of cohabitants(OR=1.70;OR=1.60),absence of vaccination(OR=3.11;OR=2.51),previous history of bowel infections(OR=1.78;OR=1.49),and family history of IBD(OR=5.26;OR=3.33).Associated risk factors for CD were age(18-39 years)(OR=1.73),higher educational level(OR=2.22),absence of infectious childhood diseases(OR=1.99).The UC predictive variables were living in an urban area(OR=1.62),inadequate living conditions(OR=1.48)and former smokers(OR=3.36).Appendectomy was a risk factor for CD(OR=1.58)with inverse association with UC(OR=4.79).Consumption of treated and untreated water was associated with risk of CD(OR=1.38)and UC(OR=1.53),respectively.CONCLUSION This is the first examining environmental exposures as risk factors for inflammatory bowel disease in Brazil.Most of the variables associated with disease risk support the role of the hygiene hypothesis in IBD development.
文摘Pneumonia, a respiratory infection induces acute or chronic inflammation, characterized by increased activity of lymphocytes and neutrophils, thus generating oxygen-free radicals that decrease the endogenous antioxidants defence system. The aim of this experimental study focused on the capacity of nontoxic aqueous, hydroethanolic and ethanolic extracts of Greenwayodendron suaveolens (Engl. & Diels) Verdc. subsp. suaveolens to regulate free reactive species and protein inflammation generated by infectious disease. The phytochemical screenings of G. suaveolens extracts were carried out according to precipitation and colorimetric methods. The total antioxidant and flavonoid contents were determined by the Folin-Ciocalteu and Aluminium Chloride ethanolic methods. The efficiency of G. suaveolens extracts on free radicals was evaluated using DPPH<sup>•</sup>, ABTS<sup>+•</sup>, and FRAP methods. The anti-inflammatory properties of extracts were evaluated according to in vitro protein (BSA) denaturation, Proteinase Inhibitory Action, and Red Blood Cell Membrane stabilization assays. The G. suaveolens aqueous, hydroethanolic and ethanolic extracts were used for the acute toxicity assessment according to the OECD protocol. The obtained results showed the presence of flavonoids, phenols, polyphenols, tannins, anthocyanins, alkaloids, terpenoids, and sterols as secondary metabolites families in G. suaveolens extracts. The highest contents of total antioxidants and flavonoids were highlighted in the hydroethanolic extract. However, it’s the G. suaveolens aqueous extract that showed the best free radical DPPH<sup>•</sup> and ABTS<sup>+•</sup> scavenging activities (SC<sub>50</sub>) of 11.06 μg/mL and 15.16 μg/mL respectively. The highest ferric-reducing activity was found in G. suaveolens ethanolic extract with 866.23 μg EGA/mg of dry weight. The hydroethanolic extract has shown a high anti-inflammatory activity through BSA denaturation and erythrocyte membrane haemolysis with inhibitory concentrations 50 (IC<sub>50</sub>) of 48.63 and 59.22 μg/mL respectively. In contrast, proteinase inhibitory activity revealed a better potential of IC<sub>50</sub> (34.19 μg/mL) for the ethanolic extract. In oral acute toxicity, all treated groups revealed neither mortality nor any significant alteration in behaviour and locomotion. The lethal dose 50 (LD<sub>50</sub>) of G. suaveolens extracts was >5000 mg/kg. These results suggest that G. suaveolens stem-barks extracts may serve as therapeutic sources to prevent inflammation induced by oxidative stress, an important feature of infectious diseases.
文摘This work focuses on the design of a new type of eco-material based on Typha“Domingensis”and clay from the south of the Republic of Benin through various dosages.Three particle size classes of typha shavings were selected to be mixed with two types of clayin order to make parallelepiped shaped samples ready for experimentation.The massive use of these briquettes thus obtained,in the construction of habitats,would not only contribute to reducing the energy consumption inside the dwellings but also would limit the invasion of the waterways of Benin,which would facilitate navigation,fishing and river sanitation activities.In addition,this biosourced,low-polluting material would contribute to improving the energy transition by integrating it into rehabilitation of buildings.
基金supported by the National Natural Science Foundation of China(No.82204925)the Financial Project of Fujian Province(No.X2024004)the Natural Science Foundation of Fujian Province,China(No.2024J01782,2022J01368)。
文摘Objective:This study investigates the efficacy and mechanisms of Qingjie Fuzheng Granules(QFG)in inhibiting colitis-associated colorectal cancer(CAC)development via RNA sequencing(RNA-seq)and16S ribosomal RNA(rRNA)correlation analysis.Methods:CAC was induced in BALB/c mice using azoxymethane(AOM)and dextran sulfate sodium(DSS),and QFG was administered orally to the treatment group.The effects of QFG on CAC were evaluated using disease index,histology,and serum T-cell ratios.RNA-seq and 16S rRNA analysis assessed the transcriptome and microbiome change.Key pharmacodynamic pathways were identified by integrating these data and confirmed via Western blotting and immunofluorescence.The link between microbiota and CACrelated markers was explored using linear discriminant analysis effect size and Spearman correlation analysis.Results:Long-term treatment with QFG prevented AOM/DSS-induced CAC formation,reduced levels of interleukin(IL)-1βtumor necrosis factor-alpha(TNF-α),IL-6,and interferon y(IFN-y),and increased CD3^(+)and CD4^(+)/CD8^(+)T cells ratio,without causing hepatic or renal toxicity.A 16S rRNA analysis revealed that QFG rebalanced the Firmicutes/Bacteroidetes ratio and mitigated AOM/DSS-induced microbiota disturbances.Transcriptomics and Western blotting analysis identified the nucleotide-binding oligomerization domain-containing protein 2(NOD2)/nuclear factor kappa-B(NF-κB)pathway as key for QFG's treatment against CAC.Furthermore,QFG decreased the abundance of Bacilli,Bacillales,Staphylococcaceae,Staphylococcus,Lactobacillales,Aerococcus,Alloprevotella,and Akkermansia,while increasing Clostridiales,Lachnospiraceae,LachnospiraceaeNK4A136group,Ruminococcaceae,and Muribaculaceae,which were highly correlated with CAC-related markers or NOD2/NF-kB pathway.Conclusion:By mapping the relationships between CAC,immune responses,microbiota,and key pathways,this study clarifies the mechanism of QFG in inhibiting CAC,highlighting its potential for clinical use as preventive therapy.
文摘Background Spinal cord injury （SCI） is a complex trauma that consists of multiple pathological mechanisms involving cytotoxic, oxidation stress and immune-endocrine. This study aimed to establish plasma metabonomics fingerprinting atlas for SCI using 1H nuclear magnetic resonance （NMR） based metabonomics methodology and principal component analysis techniques.Methods Nine Sprague-Dawley （SD） male rats were randomly divided into SCI, normal and sham-operation control groups. Plasma samples were collected for 1H NMR spectroscopy 3 days after operation. The NMR data were analyzed using principal component analysis technique with Matlab software.Results Metabonomics analysis was able to distinguish the three groups （SCI, normal control, sham-operation）. The fingerprinting atlas indicated that, compared with those without SCI, the SCI group demonstrated the following characteristics with regard to second principal component： it is made up of fatty acids, myc-inositol, arginine, very low-density lipoprotein （VLDL）, low-density lipoprotein （LDL）, triglyceride （TG）, glucose, and 3-methyl-histamine.Conclusions The data indicated that SCI results in several significant changes in plasma metabolism early on and that a metabonomics approach based on 1H NMR spectroscopy can provide a metabolic profile comprising several metabolite classes and allow for relative quantification of such changes. The results also provided support for further development and application of metabonomics technologies for studying SCI and for the utilization of multivariate models for classifying the extent of trauma within an individual.
基金This study was partly supported by American Heart Association grant number 12SDG11950003National Institutes of Health(NIH)grant number NS081299.
文摘Small ubiquitin-like modifier(SUMO)conjugation(SUMOylation)is a post-translational protein modification that modulates almost all major cellular processes,and has been implicated in many human diseases.A growing body of evidence from in vitro and in vivo studies demonstrates that increasing global levels of SUMO conjugated proteins(global SUMOylation)protects cells against ischaemia-induced damage,while suppressing global SUMOylation promotes cell injury after ischaemia.Indeed,SUMOylation has emerged as a potential therapeutic target for neuroprotection in brain ischaemia,including global brain ischaemia and focal brain ischaemia(ischaemic stroke).Here,we summarise findings on the role of SUMOylation in human diseases,brain ischaemia in particular,and review recent developments in drug discovery targeting SUMOylation with a major focus on its neuroprotective applications.
基金grants from Sichuan Provincial Department of Science and Technology(2012SZ0181,SZ20120209)grants from Chengdu Municipality Department of Science and Technology(11PPYB099SF-289 AND 12PPYB181SF-002).
文摘Background:We aimed to systematically review the efficacy of mannitol(MTL)on patients with acute severe traumatic brain injury(TBI).Methods:Databases such as PubMed(US National Library of Medicine),CENTRAL(The Cochrane Library 2014,Issue 3),ISI(Web of Science:Science Citation Index Expanded),Chinese Biomedicine Database(CBM),and China Knowledge Resource Integrated Database(CNKI)have been searched for relevant studies published between 1 January 2003 and 1 October 2014.We have established inclusion and exclusion criteria to identify RCTs,which were suitable to be enrolled in the systematic review.The comparison group could be hypertonic saline(HS),hydroxyethyl starch,or others.The quality assessment was based on the Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.1 and modified Jadad score scale.The major outcome was mortality,followed by the secondary outcomes such as neurological outcome,days on intensive care unit(ICU),and ventilator day.In addition,intracranial pressure(ICP),cerebral perfusion pressure(CPP),and mean arterial pressure(MAP)were used as the surrogate endpoints.Data synthesis and meta-analysis was conducted by using R(version 3.7-0.).Results:When 176 potential relevant literatures and abstracts have been screened,four RCTs met all the inclusion criteria and were enrolled for the meta-analysis.Amongst all the enrolled studies,two trials have provided the primary outcome data.There was no heterogeneity between two studies(I2=0%)and a fixed model was used for meta-analysis(n=53),pooled result indicated that the mortality was similar in mannitol intervention and control treatment,OR=0.80,95%CI[0.27,2.37],P=0.38.We found that both mannitol and HS were efficient in decreasing the ICP.Furthermore,the effect of the HS on the ICP appeared to be more effective in the patients with diffuse brain injuries than mannitol did.Conclusions:As a conclusion,the mannitol therapy cannot reduce the mortality risk of acute severe traumatic brain injury.Current evidence does not support the mannitol as an effective treatment of acute severe traumatic brain injury.The well-designed randomized controlled trials are in urgent need to demonstrate the adoption of mannitol to acute severe traumatic brain injury.
基金supported in part by the National Science and Technology Major Project(No.2021 YFC2301803)Shenzhen Fund for Guangdong Provincial High-Level Clinical Key Specialties(No.SZGSP011)+2 种基金Science and Technology Program of Shenzhen,China(No.JCYJ 20230807143411023)the clinical research project of Shenzhen Third Peoples Hospital(No.G2022044)the Teaching Quality and Teaching Reform Project of Education Department of Guangdong Province:Experimental Teaching Demonstration Center of Emerging Infectious Diseases(Y01411846).
文摘Inborn errors of the signal transducer and activator of transcription 1(STAT1)result in four types of immunodeficiency disease with varying degrees of impaired STAT1 function:autosomal recessive(AR)complete STAT1 deficiency,AR partial STAT1 deficiency,autosomal dominant(AD)STAT1 deficiency,and AD STAT1 gain-of-function(STAT1-GOF).Of which,the STAT1-GOF mutations promote a clinical syndrome of immune dysregulation characterized by recurrent infections,especially chronic mucocutaneous candidiasis(CMC)and Talaromyces marneffei infection and predisposition to humoral autoimmunity.STAT1-GOF mutations lead to enhanced phosphorylation of STAT1(pSTAT1),delayed dephosphorylation,and impaired nuclear dephosphorylation.As a result,the development of T helper(Th)17 cells is impaired,limiting the production of interleukin(IL)-17,which plays an important role in antifungal immunity.Additionally,mutations can also cause a decrease in the proportion of CD4^(+),CD8^(+),and natural killer(NK)cells.Recent research demonstrated that in the absence of overt infection,STAT-GOF mice can disrupt naïve CD4^(+)T cell homeostasis and promote expansion and differentiation of abnormal T-follicular helper/T-helper 1-like(Tfh/Th1-like)T cells and germinal center-like(GC-like)B cells,and thus reminds us of the complex molecular mechanism of autoimmune disease with/without fungal infection,which may further involve specific clinical treatment including antifungal and anti-autoimmunity therapies.In addition,sex and location of mutation were also associated with the clinical phenotype.Individuals with DNA binding domain(DBD)mutations had a higher prevalence of autoimmunity and aberrant B cell activation.Disrupted CD4^(+)T cell homeostasis occurred sooner and more robustly in females,highlighting the importance of specific treatment to normalize STAT1 expression and restore immune tolerance in patients with STAT1-GOF syndrome.Herein,we provide a comprehensive review of STAT1-GOF aiming to further clarify the regulatory mechanism of cellular and humoral immune deficiency in patients with fungal infection with or without autoimmunity.
