The use of antimicrobials without microbiological proof is frequent and contributes to the emergence of resistance. The aim was to identify the organisms isolated during laboratory examinations and the type of antimic...The use of antimicrobials without microbiological proof is frequent and contributes to the emergence of resistance. The aim was to identify the organisms isolated during laboratory examinations and the type of antimicrobials consumed by patients hospitalized to Infectious Diseases’ Clinic. This is a cross-sectional and analytical study, carried out from January 1 to December 31, 2017 in the Infectious Diseases Department of Point “G” Teaching Hospital in Mali. All biological specimens from patients during the study period were analyzed. In total, 322 patients benefited from microbiological test, with a mean age of 40.9 ± 12.2 years (range 15 and 74 years) with a sex ratio of 0.93. Only 5.6% of patients were HIV negative. In all participants, a total of 658 microbiological specimen were taken, 224 (34.0%) identified at least one pathogen including bacteria in more than a half of the cases (58.5%). On the report of bacteriological analysis, the most frequently identified organisms were <i>Mycobacterium tuberculosis</i> (42.2%) mainly in sputum;<i>Escherichia coli</i> (24.2%) and <i>Klebsiella pneumoniae</i> (7.8%) commonly in urine and <i>Gardnerella vaginalis</i> (7.0%) exclusively in vaginal secretions. <i>Candida albicans</i> (5/8) and <i>Cryptococcus neoformans</i> (3/8) were the most common fungi while <i>Plasmodium falciparum</i> (96.4%) represented the parasite frequently found in blood. From a therapeutic standpoint, 1143 antimicrobials were prescribed to 322 admitted patients, <i>i.e.</i> 3.55 anti-infectives per patient. Antibiotics (excluding tuberculosis drugs), antiparasitics and antifungals represented respectively 46.2%;18.8% and 15.1% of anti-infectives. Antibiotic therapy was effective in 274 (85.1%) patients and among them, only 76 (27.7%) cases were based on microbiological evidence. Antibiotics are the most widely used antimicrobials in an infectious disease department. Empiric treatments are common but must be minimized by the search for microbiological evidence.展开更多
Pancreatic cancer remains one of the most challenging malignancies to treat,with a poor prognosis and limited therapeutic options.Despite the success of immunotherapy and targeted therapies for other cancers,these app...Pancreatic cancer remains one of the most challenging malignancies to treat,with a poor prognosis and limited therapeutic options.Despite the success of immunotherapy and targeted therapies for other cancers,these approaches have not yet transformed the treatment landscape for pancreatic cancer.The unique tumor microenvironment(TME)of pancreatic cancer,characterized by dense fibrotic stroma and immunosuppressive myeloid cells,poses significant barriers to effective immunotherapy.Current research highlights the need for an in-depth understanding of the TME and the development of strategies to overcome its immunosuppressive properties.Recent studies have explored various immunotherapeutic approaches,including immune checkpoint inhibitors,cancer vaccines,and adoptive cell therapies,some of which have shown promising results in preclinical and early clinical trials.Furthermore,combining immunotherapy with traditional treatments,such as chemotherapy and radiotherapy,has shown potential for enhancing antitumor efficacy,although targeted therapies for pancreatic cancer are still in their early stages and are being investigated for their ability to disrupt specific molecular pathways involved in tumor growth and survival.This review provides a comprehensive overview of the advances in immunotherapy and targeted therapies for pancreatic cancer,discussing the current state of research,clinical outcomes,and future directions for improving patient prognosis.展开更多
AIM： To assess the value of widely used clinical scores in the early identification of acute pancreatitis （AP） patients who are likely to suffer from intra-abdominal hypertension （IAH） and abdominal compartment s...AIM： To assess the value of widely used clinical scores in the early identification of acute pancreatitis （AP） patients who are likely to suffer from intra-abdominal hypertension （IAH） and abdominal compartment syndrome （ACS）.METHODS： Patients （η = 44） with AP recruited in this study were divided into two groups （ACS and non-ACS） according to intra-abdominal pressure （IAP） determined by indirect measurement using the transvesical route via Foley bladder catheter. On admission and at regular intervals, the severity of the AP and presence of organ dysfunction were assessed utilizing different multifactorial prognostic systems： Glasgow-Imrie score, Acute Physiology and Chronic Health Evaluation Ⅱ （APACHE-Ⅱ） score, and Multiorgan Dysfunction Score （MODS）. The diagnostic performance of scores predicting ACS development, cut-off values and specificity and sensitivity were established using receiver operating characteristic （ROC） curve analysis.RESULTS： The incidence of ACS in our study population was 19.35%. IAP at admission in the ACS group was 22.0 （18.5-25.0） mmHg and 9.25 （3.0-12.4） mmHg in the non-ACS group （P 〈 0.01）. Univariate statistical analysis revealed that patients in the ACS group had significantly higher multifactorial clinical scores （APACHE Ⅱ, Glasgow-Imrie and MODS） on admission and higher maximal scores during hospitalization （P 〈 0.01）. ROC curve analysis revealed that APACHE Ⅱ, Glasgow-Imrie, and MODS are valuable tools for early prediction of ACS with high sensitivity and specificity, and that cut-off values are similar to those used for stratification of patients with severe acute pancreatitis （SAP）.CONCLUSION： IAH and ACS are rare findings in patients with mild AR Based on the results of our study we recommend measuring the IAP in cases when patients present with SAP （APACHE Ⅱ 〉 7; MODS 〉 2 or Glasgow-Imrie score 〉 3）.展开更多
AIM： To assess if the included vascular endothelial growth factor （VEGF） polymorphisms rs3025035, rs3025021 and rs2010963 are associated to proliferative retinopathy in a Mexican population with type 2 diabetes mel...AIM： To assess if the included vascular endothelial growth factor （VEGF） polymorphisms rs3025035, rs3025021 and rs2010963 are associated to proliferative retinopathy in a Mexican population with type 2 diabetes mellitus （T2DM）. METHODS： A case-control study was conducted in adult individuals with T2DM associated to proliferative retinopathy or non-proliferative retinopathy from Oct. 2014 to Jun. 2015 from the Retina Department of the Asociation to Prevent Blindness in Mexico. The selected patients were adults with a diagnosis of T2DM ≥5y. All subjects had a comprehensive ocular examination and the classification of the retinopathy severity was made considering the Early Treatment Diabetic Retinopathy Study （ETDRS） standardization protocols. Genomic DNA was extracted from whole fresh blood. All samples were genotyped by qPCR for selected VEGF polymorphisms. Hardy-Weinberg equilibrium was calculated by comparing Chi-square values between the expected and the observed values for genotype counts.RESULTS： In total 142 individuals were enrolled, 71 individuals with T2DM and associated proliferative retinopathy and 71 individuals with non-proliferative retinopathy. One-sided Fisher’s exact test was performed for rs3025021 [OR （95% CI）=0.44（0.08-2.2）; P=0.25] and rs2010963 [OR （95% CI）=0.63（0.25-1.6）; P=0.23]. The minor allelic frequencies obtained were 26% for rs3025021, 10% for rs3025035 and 61% for rs2010963. The pairwise linkage disequilibrium between the three SNP was assessed, and was as follows： rs3025021 vs rs3025035： D’=1.0, r2=0.1043, P≤0.0001; rs3025021 vs rs2010963： D’=0.442, r2=0.0446, P=0.149; rs3025035 vs rs2010963： D’=0.505, r2=0.0214, P=0.142.CONCLUSION： This is the first analysis involving VEGF polymorphisms and proliferative diabetic retinopathy in a Mexican population. A major finding of the present study is that none of the polymorphisms studied was significantly associated with proliferative retinopathy. Based on these results, we can infer that different populations have different associations for the same polymorphisms.展开更多
Background:Probiosis is considered a potential strategy to reduce antibiotics use and prevent postweaning diarrhea(PWD).This study investigated the effect of Bacillus amyloliquefaciens DSM25840 or Bacillus subtilis DS...Background:Probiosis is considered a potential strategy to reduce antibiotics use and prevent postweaning diarrhea(PWD).This study investigated the effect of Bacillus amyloliquefaciens DSM25840 or Bacillus subtilis DSM25841 supplementation on growth,health,immunity,intestinal functionality and microbial profile of post-weaning pigs after enterotoxigenic E.coli(ETEC)F4 challenge.Methods:Sixty-four post-weaning piglets(7748 g±643 g)were randomly al ocated to four groups:control basal diet(CO);CO+1.28×10~6 CFU/g of B.amyloliquefaciens(BAA);CO+1.28×10~6 CFU/g feed of B.subtilis(BAS);CO+1 g colistin/kg of feed(AB).At day(d)7,animals were chal enged with 10~5 CFU/m L of ETEC F4 ac O149 and then fol owed for fecal score and performance until d 21.Blood was col ected at d 6,d 12 and d 21 for immunoglobulins,at d 8 for acute phase proteins,at d 8 and d 21 for metabolomics analysis.Jejunum was sampled for morphometry,quantification of apoptosis,cel proliferation,neutral and acid mucine and Ig A secretory cel s,and microarray analysis at d 21.Jejunum and cecum contents were col ected for microbiota at d 21.Results:AB and BAS reduced the fecal score impairment compared to CO(P<0.05)at d 14.Body weight(BW),average daily weight gain(ADWG),average daily feed intake(ADFI)and gain to feed ratio(G:F)did not differ between Bacil us groups and CO.AB improved BW at d 7,d 14 and d 21,ADWG ADFI and G:F from d 0 to d 7(P<0.05).At d 8,CO had higher plasma arginine,lysine,ornithine,glycine,serine and threonine than other groups,and higher haptoglobin than AB(P<0.05).At d 21,CO had lower blood glycine,glutamine and Ig A than BAS.Morphology,cel s apoptosis and mucins did not differ.BAS and AB increased the vil us mitotic index.Transcriptome profile of BAS and AB were more similar than CO.Gene sets related to adaptive immune response were enriched in BAA,BAS and AB.CO had enriched gene set for nuclear structure and RNA processing.CO had a trend of higher Enterobacteriaceae in cecum than the other groups(P=0.06).Conclusion:Bacil us subtilis DSM25841 treatment may reduce ETEC F4ac infection in weaned piglets,decreasing diarrhea and influencing mucosal transcriptomic profile.展开更多
BACKGROUND Septic arthritis is an orthopedic emergency requiring immediate surgical intervention.Current diagnostic standard of care is an invasive joint aspiration.Aspirations provide information about the inflammato...BACKGROUND Septic arthritis is an orthopedic emergency requiring immediate surgical intervention.Current diagnostic standard of care is an invasive joint aspiration.Aspirations provide information about the inflammatory cells in the sample within a few hours,but there is often ambiguity about whether the source is infectious(e.g.bacterial)or non-infectious(e.g.gout).Cultures can take days to result,so decisions about surgery are often made with incomplete data.Novel diagnostics are thus needed.The“Sepsis MetaScore”(SMS)is an 11-mRNA host immune blood signature that can distinguish between infectious and noninfectious acute inflammation.It has been validated in multiple cohorts across heterogeneous clinical settings.AIM To study whether the SMS holds diagnostic validity in determining the etiology of acute arthritis.METHODS We conducted a blinded,prospective,non-interventional clinical study of the SMS.All patients undergoing work-up for a septic primary joint were enrolled.Patients proceeded through the normal standard-of-care pathway,including joint aspiration and inflammatory labs[white blood cell(WBC),erythrocyte sedimentation rate(ESR),C-reactive protein(CRP)].Venous blood was also drawn into PAX gene RNA-stabilizing tubes and mRNAs were measured using Nano String nCounter?.SMS was calculated blinded to clinical results.RESULTS A total of 20 samples were included,of which 11 were infected based on aspiration or intra-operative cultures.The SMS had an area under the ROC curve(AUROC)of 0.87 for separating infectious from non-infectious conditions.For comparison,the AUROCs for ESR=0.58,CRP=0.6,and WBC=0.59.At 100%sensitivity for infection,the specificity of the SMS was 40%,meaning nearly half of non-septic patients could have been ruled out for further intervention.CONCLUSION In this pilot study,SMS showed a high level of diagnostic accuracy in predicting septic joints compared to other diagnostic biomarkers.This quick blood test could be an important tool for early,accurate identification of acute septic joints and need for emergent surgery,improving clinical care and healthcare spending.展开更多
AIM： To explore the role of ghrelin in gallstone disease. METHODS： We carried out a cross-sectional study in 150 subjects, 38 with gallstones （cases） and 112 controls. We also did a real-time PCR-RT study in twent...AIM： To explore the role of ghrelin in gallstone disease. METHODS： We carried out a cross-sectional study in 150 subjects, 38 with gallstones （cases） and 112 controls. We also did a real-time PCR-RT study in twenty gallbladder samples each. Body mass index （BNI）, serum insulin, ghrelin, and serum lipids were measured. Logistic regression analyses （univariate and multivariate） were conducted to estimate the probability of gallstone disease associated with serum ghrelin concentrations. RESULTS： Cases were statistically different from controls in gender distribution （P = 0.01）, age （53 vs 44 yr, P = 0.002）, BNI （28 vs 25; P = 0.004）, and glucose （5.26 vs 4.98 mmol/L; P = 0.05）. The prevalence of ghrelin serum levels above the third tercile was lower in subjects without metabolic syndrome （P 〈 0.05）. In a multivariate model, we found a protective effect, when ghrelin values were higher than the median value （OR = 0.27, 95%CI 0.09-0.82, P = 0.02）. Twenty （20%） gallbladder specimens expressed ghrelin mRNA. CONCLUSION： Serum ghrelin concentrations are associated with a protective effect of GD.展开更多
A proposition based on the fluctuation theorem in thermodynamics is formulated to quantitatively describe molecular evolution processes in biology. Although we cannot give full proof of its generality, we demonstrate ...A proposition based on the fluctuation theorem in thermodynamics is formulated to quantitatively describe molecular evolution processes in biology. Although we cannot give full proof of its generality, we demonstrate via computer simulation its applicability in an example of DNA in vitro evolution. According to this theorem, the evolution process is a series of exponentially rare fluctuations fixed by the force of natural selection展开更多
This paper exploits the Rayleigh integral method to simulate the propagation of transmitted ultrasonic waves and received echoes through various media. Performed simulations study the effect of apodization using diffe...This paper exploits the Rayleigh integral method to simulate the propagation of transmitted ultrasonic waves and received echoes through various media. Performed simulations study the effect of apodization using different types of windows and the effect of medium properties on the reflections obtained. All estimations are done using the Rayleigh integral method simplified by the Fresnel approximation. Five different interfaces are considered： tissue-bone-tissue, tissue-fat-bone, fat-muscle-bone, air-fat-bone and water-fat-bone. The apodization simulations show that the hamming window is more efficient than the rectangular and triangular windows for obtaining a more consistent beam. In the second set of simulations, reflections are mapped with respect to the depth from which these reflections are generated. It demonstrates that the solid and water media allow for the attainment of echoes from deeper regions as compared to the air medium. Matlab is used as the simulation framework.展开更多
Immune thrombocytopenic purpura(ITP)is an autoimmune disorder characterized by autoantibody-mediated platelet destruction and impaired platelet production,leading to bleeding risk at platelet counts<100×10^(9)...Immune thrombocytopenic purpura(ITP)is an autoimmune disorder characterized by autoantibody-mediated platelet destruction and impaired platelet production,leading to bleeding risk at platelet counts<100×10^(9)/L.In adults,ITP often becomes chronic and recurrent,necessitating multiple lines of therapy,including corticosteroids,intravenous immunoglobulins,splenectomy,rituximab,thrombopoietin receptor agonists(TPO-RAs),and fostamatinib.Yet a subset of patients remains relapsed/refractory(r/r),with residual autoantibody-producing plasma cells driving persistent disease.Standard immunosuppression,as is the case of rituximab,targets CD20+B lymphocytes and might spare long-lived plasma cells(LLPCs).Autoantibodies persist if LLPCs survive.Daratumumab binds CD38 expressed on plasmablasts and plasma cells,including LLPCs;and depletes them efficiently,removing autoantibody sources.展开更多
Introduction:Coronavirus disease 2019(COVID-19)may be associated with various skin manifestations.Among them,figurate erythema(FE)is rare;only a few clinical reports have been published.Herein,we reported an unusual c...Introduction:Coronavirus disease 2019(COVID-19)may be associated with various skin manifestations.Among them,figurate erythema(FE)is rare;only a few clinical reports have been published.Herein,we reported an unusual concentric FE lesions and their immunohistochemical profile in a patient with COVID-19.Case presentation:A 52-year-old woman was diagnosed with COVID-19.One month later,she developed asymptomatic annular erythematous concentric ring lesions on her inner right thigh.The margin of every ring increased in coloration,and the lesions then completely resolved in 2 weeks.A biopsy revealed vasculitis of small vessels,an increase in the fluorescence intensity of CD3 and CD45,and negativity for COVID-19 RNA.Discussion:The results showed an unusual FE that has a clinical mixed type between erythema annulare centrifugum and erythema gyratum repens;the physiopathological mechanism in the FE due to COVID-19 is unknown;one theory involves rapid viral passage into the cutaneous vascular system that triggers an immune and inflammatory response.Although the results exhibited a negative COVID-19 RNA in the tissue,the CD3^(+)/CD45^(+)lymphocyte infiltration could explain the clinical pattern as a direct inflammatory response in the small vessel or as a delayed immune response.Conclusion:Our findings suggest an immunohistochemical small vessel vasculitis pattern with an unusual clinical FE that differs from other types of COVID-19-associated FE or erythema reported previously.展开更多
The biosynthesis of host lipids and/or lipid droplets(LDs)has been studied extensively as a putative therapeutic target in diverse viral infections.However,directly targeting the LD lipolytic catabolism in virus-infec...The biosynthesis of host lipids and/or lipid droplets(LDs)has been studied extensively as a putative therapeutic target in diverse viral infections.However,directly targeting the LD lipolytic catabolism in virus-infected cells has not been widely investigated.Here,we show the linkage of the LD-associated lipase activation to the breakdown of LDs for the generation of free fatty acids(FFAs)at the late stage of diverse RNA viral infections,which represents a broad-spectrum antiviral target.Dysfunction of membrane transporter systems due to virus-induced cell injury results in intracellular malnutrition at the late stage of infection,thereby making the virus more dependent on the FFAs generated from LD storage for viral morphogenesis and as a source of energy.The replication of SARS-CoV-2 and influenza A virus(IAV),which is suppressed by the treatment with LD-associated lipases inhibitors,is rescued by supplementation with FFAs.The administration of lipase inhibitors,either individually or in a combination with virus-targeting drugs,protects mice from lethal IAV infection and mitigates severe lung lesions in SARS-CoV-2-infected hamsters.Moreover,the lipase inhibitors significantly reduce proinflammatory cytokine levels in the lungs of SARS-CoV-2-and IAV-challenged animals,a cause of a cytokine storm important for the critical infection or mortality of COVID-19 and IAV patients.In conclusion,the results reveal that lipase-mediated intracellular LD lipolysis is commonly exploited to facilitate RNA virus replication and furthermore suggest that pharmacological inhibitors of LD-associated lipases could be used to curb current COVID-19-and future pandemic outbreaks of potentially troublesome RNA virus infection in humans.展开更多
文摘The use of antimicrobials without microbiological proof is frequent and contributes to the emergence of resistance. The aim was to identify the organisms isolated during laboratory examinations and the type of antimicrobials consumed by patients hospitalized to Infectious Diseases’ Clinic. This is a cross-sectional and analytical study, carried out from January 1 to December 31, 2017 in the Infectious Diseases Department of Point “G” Teaching Hospital in Mali. All biological specimens from patients during the study period were analyzed. In total, 322 patients benefited from microbiological test, with a mean age of 40.9 ± 12.2 years (range 15 and 74 years) with a sex ratio of 0.93. Only 5.6% of patients were HIV negative. In all participants, a total of 658 microbiological specimen were taken, 224 (34.0%) identified at least one pathogen including bacteria in more than a half of the cases (58.5%). On the report of bacteriological analysis, the most frequently identified organisms were <i>Mycobacterium tuberculosis</i> (42.2%) mainly in sputum;<i>Escherichia coli</i> (24.2%) and <i>Klebsiella pneumoniae</i> (7.8%) commonly in urine and <i>Gardnerella vaginalis</i> (7.0%) exclusively in vaginal secretions. <i>Candida albicans</i> (5/8) and <i>Cryptococcus neoformans</i> (3/8) were the most common fungi while <i>Plasmodium falciparum</i> (96.4%) represented the parasite frequently found in blood. From a therapeutic standpoint, 1143 antimicrobials were prescribed to 322 admitted patients, <i>i.e.</i> 3.55 anti-infectives per patient. Antibiotics (excluding tuberculosis drugs), antiparasitics and antifungals represented respectively 46.2%;18.8% and 15.1% of anti-infectives. Antibiotic therapy was effective in 274 (85.1%) patients and among them, only 76 (27.7%) cases were based on microbiological evidence. Antibiotics are the most widely used antimicrobials in an infectious disease department. Empiric treatments are common but must be minimized by the search for microbiological evidence.
文摘Pancreatic cancer remains one of the most challenging malignancies to treat,with a poor prognosis and limited therapeutic options.Despite the success of immunotherapy and targeted therapies for other cancers,these approaches have not yet transformed the treatment landscape for pancreatic cancer.The unique tumor microenvironment(TME)of pancreatic cancer,characterized by dense fibrotic stroma and immunosuppressive myeloid cells,poses significant barriers to effective immunotherapy.Current research highlights the need for an in-depth understanding of the TME and the development of strategies to overcome its immunosuppressive properties.Recent studies have explored various immunotherapeutic approaches,including immune checkpoint inhibitors,cancer vaccines,and adoptive cell therapies,some of which have shown promising results in preclinical and early clinical trials.Furthermore,combining immunotherapy with traditional treatments,such as chemotherapy and radiotherapy,has shown potential for enhancing antitumor efficacy,although targeted therapies for pancreatic cancer are still in their early stages and are being investigated for their ability to disrupt specific molecular pathways involved in tumor growth and survival.This review provides a comprehensive overview of the advances in immunotherapy and targeted therapies for pancreatic cancer,discussing the current state of research,clinical outcomes,and future directions for improving patient prognosis.
文摘AIM： To assess the value of widely used clinical scores in the early identification of acute pancreatitis （AP） patients who are likely to suffer from intra-abdominal hypertension （IAH） and abdominal compartment syndrome （ACS）.METHODS： Patients （η = 44） with AP recruited in this study were divided into two groups （ACS and non-ACS） according to intra-abdominal pressure （IAP） determined by indirect measurement using the transvesical route via Foley bladder catheter. On admission and at regular intervals, the severity of the AP and presence of organ dysfunction were assessed utilizing different multifactorial prognostic systems： Glasgow-Imrie score, Acute Physiology and Chronic Health Evaluation Ⅱ （APACHE-Ⅱ） score, and Multiorgan Dysfunction Score （MODS）. The diagnostic performance of scores predicting ACS development, cut-off values and specificity and sensitivity were established using receiver operating characteristic （ROC） curve analysis.RESULTS： The incidence of ACS in our study population was 19.35%. IAP at admission in the ACS group was 22.0 （18.5-25.0） mmHg and 9.25 （3.0-12.4） mmHg in the non-ACS group （P 〈 0.01）. Univariate statistical analysis revealed that patients in the ACS group had significantly higher multifactorial clinical scores （APACHE Ⅱ, Glasgow-Imrie and MODS） on admission and higher maximal scores during hospitalization （P 〈 0.01）. ROC curve analysis revealed that APACHE Ⅱ, Glasgow-Imrie, and MODS are valuable tools for early prediction of ACS with high sensitivity and specificity, and that cut-off values are similar to those used for stratification of patients with severe acute pancreatitis （SAP）.CONCLUSION： IAH and ACS are rare findings in patients with mild AR Based on the results of our study we recommend measuring the IAP in cases when patients present with SAP （APACHE Ⅱ 〉 7; MODS 〉 2 or Glasgow-Imrie score 〉 3）.
基金Supported by a grant from the Asociation to Prevent Blindness in Mexico(No.RE-14-02)
文摘AIM： To assess if the included vascular endothelial growth factor （VEGF） polymorphisms rs3025035, rs3025021 and rs2010963 are associated to proliferative retinopathy in a Mexican population with type 2 diabetes mellitus （T2DM）. METHODS： A case-control study was conducted in adult individuals with T2DM associated to proliferative retinopathy or non-proliferative retinopathy from Oct. 2014 to Jun. 2015 from the Retina Department of the Asociation to Prevent Blindness in Mexico. The selected patients were adults with a diagnosis of T2DM ≥5y. All subjects had a comprehensive ocular examination and the classification of the retinopathy severity was made considering the Early Treatment Diabetic Retinopathy Study （ETDRS） standardization protocols. Genomic DNA was extracted from whole fresh blood. All samples were genotyped by qPCR for selected VEGF polymorphisms. Hardy-Weinberg equilibrium was calculated by comparing Chi-square values between the expected and the observed values for genotype counts.RESULTS： In total 142 individuals were enrolled, 71 individuals with T2DM and associated proliferative retinopathy and 71 individuals with non-proliferative retinopathy. One-sided Fisher’s exact test was performed for rs3025021 [OR （95% CI）=0.44（0.08-2.2）; P=0.25] and rs2010963 [OR （95% CI）=0.63（0.25-1.6）; P=0.23]. The minor allelic frequencies obtained were 26% for rs3025021, 10% for rs3025035 and 61% for rs2010963. The pairwise linkage disequilibrium between the three SNP was assessed, and was as follows： rs3025021 vs rs3025035： D’=1.0, r2=0.1043, P≤0.0001; rs3025021 vs rs2010963： D’=0.442, r2=0.0446, P=0.149; rs3025035 vs rs2010963： D’=0.505, r2=0.0214, P=0.142.CONCLUSION： This is the first analysis involving VEGF polymorphisms and proliferative diabetic retinopathy in a Mexican population. A major finding of the present study is that none of the polymorphisms studied was significantly associated with proliferative retinopathy. Based on these results, we can infer that different populations have different associations for the same polymorphisms.
基金partly financially supported by Chr.Hansen A/S(Denmark).
文摘Background:Probiosis is considered a potential strategy to reduce antibiotics use and prevent postweaning diarrhea(PWD).This study investigated the effect of Bacillus amyloliquefaciens DSM25840 or Bacillus subtilis DSM25841 supplementation on growth,health,immunity,intestinal functionality and microbial profile of post-weaning pigs after enterotoxigenic E.coli(ETEC)F4 challenge.Methods:Sixty-four post-weaning piglets(7748 g±643 g)were randomly al ocated to four groups:control basal diet(CO);CO+1.28×10~6 CFU/g of B.amyloliquefaciens(BAA);CO+1.28×10~6 CFU/g feed of B.subtilis(BAS);CO+1 g colistin/kg of feed(AB).At day(d)7,animals were chal enged with 10~5 CFU/m L of ETEC F4 ac O149 and then fol owed for fecal score and performance until d 21.Blood was col ected at d 6,d 12 and d 21 for immunoglobulins,at d 8 for acute phase proteins,at d 8 and d 21 for metabolomics analysis.Jejunum was sampled for morphometry,quantification of apoptosis,cel proliferation,neutral and acid mucine and Ig A secretory cel s,and microarray analysis at d 21.Jejunum and cecum contents were col ected for microbiota at d 21.Results:AB and BAS reduced the fecal score impairment compared to CO(P<0.05)at d 14.Body weight(BW),average daily weight gain(ADWG),average daily feed intake(ADFI)and gain to feed ratio(G:F)did not differ between Bacil us groups and CO.AB improved BW at d 7,d 14 and d 21,ADWG ADFI and G:F from d 0 to d 7(P<0.05).At d 8,CO had higher plasma arginine,lysine,ornithine,glycine,serine and threonine than other groups,and higher haptoglobin than AB(P<0.05).At d 21,CO had lower blood glycine,glutamine and Ig A than BAS.Morphology,cel s apoptosis and mucins did not differ.BAS and AB increased the vil us mitotic index.Transcriptome profile of BAS and AB were more similar than CO.Gene sets related to adaptive immune response were enriched in BAA,BAS and AB.CO had enriched gene set for nuclear structure and RNA processing.CO had a trend of higher Enterobacteriaceae in cecum than the other groups(P=0.06).Conclusion:Bacil us subtilis DSM25841 treatment may reduce ETEC F4ac infection in weaned piglets,decreasing diarrhea and influencing mucosal transcriptomic profile.
文摘BACKGROUND Septic arthritis is an orthopedic emergency requiring immediate surgical intervention.Current diagnostic standard of care is an invasive joint aspiration.Aspirations provide information about the inflammatory cells in the sample within a few hours,but there is often ambiguity about whether the source is infectious(e.g.bacterial)or non-infectious(e.g.gout).Cultures can take days to result,so decisions about surgery are often made with incomplete data.Novel diagnostics are thus needed.The“Sepsis MetaScore”(SMS)is an 11-mRNA host immune blood signature that can distinguish between infectious and noninfectious acute inflammation.It has been validated in multiple cohorts across heterogeneous clinical settings.AIM To study whether the SMS holds diagnostic validity in determining the etiology of acute arthritis.METHODS We conducted a blinded,prospective,non-interventional clinical study of the SMS.All patients undergoing work-up for a septic primary joint were enrolled.Patients proceeded through the normal standard-of-care pathway,including joint aspiration and inflammatory labs[white blood cell(WBC),erythrocyte sedimentation rate(ESR),C-reactive protein(CRP)].Venous blood was also drawn into PAX gene RNA-stabilizing tubes and mRNAs were measured using Nano String nCounter?.SMS was calculated blinded to clinical results.RESULTS A total of 20 samples were included,of which 11 were infected based on aspiration or intra-operative cultures.The SMS had an area under the ROC curve(AUROC)of 0.87 for separating infectious from non-infectious conditions.For comparison,the AUROCs for ESR=0.58,CRP=0.6,and WBC=0.59.At 100%sensitivity for infection,the specificity of the SMS was 40%,meaning nearly half of non-septic patients could have been ruled out for further intervention.CONCLUSION In this pilot study,SMS showed a high level of diagnostic accuracy in predicting septic joints compared to other diagnostic biomarkers.This quick blood test could be an important tool for early,accurate identification of acute septic joints and need for emergent surgery,improving clinical care and healthcare spending.
文摘AIM： To explore the role of ghrelin in gallstone disease. METHODS： We carried out a cross-sectional study in 150 subjects, 38 with gallstones （cases） and 112 controls. We also did a real-time PCR-RT study in twenty gallbladder samples each. Body mass index （BNI）, serum insulin, ghrelin, and serum lipids were measured. Logistic regression analyses （univariate and multivariate） were conducted to estimate the probability of gallstone disease associated with serum ghrelin concentrations. RESULTS： Cases were statistically different from controls in gender distribution （P = 0.01）, age （53 vs 44 yr, P = 0.002）, BNI （28 vs 25; P = 0.004）, and glucose （5.26 vs 4.98 mmol/L; P = 0.05）. The prevalence of ghrelin serum levels above the third tercile was lower in subjects without metabolic syndrome （P 〈 0.05）. In a multivariate model, we found a protective effect, when ghrelin values were higher than the median value （OR = 0.27, 95%CI 0.09-0.82, P = 0.02）. Twenty （20%） gallbladder specimens expressed ghrelin mRNA. CONCLUSION： Serum ghrelin concentrations are associated with a protective effect of GD.
基金Project supported by the National Natural Science Foundation of China (Grant No. 10721403)the National Basic Research Program of China (Grant No. 2007CB814802)the Jun-Zheng Foundation at Peking University
文摘A proposition based on the fluctuation theorem in thermodynamics is formulated to quantitatively describe molecular evolution processes in biology. Although we cannot give full proof of its generality, we demonstrate via computer simulation its applicability in an example of DNA in vitro evolution. According to this theorem, the evolution process is a series of exponentially rare fluctuations fixed by the force of natural selection
文摘This paper exploits the Rayleigh integral method to simulate the propagation of transmitted ultrasonic waves and received echoes through various media. Performed simulations study the effect of apodization using different types of windows and the effect of medium properties on the reflections obtained. All estimations are done using the Rayleigh integral method simplified by the Fresnel approximation. Five different interfaces are considered： tissue-bone-tissue, tissue-fat-bone, fat-muscle-bone, air-fat-bone and water-fat-bone. The apodization simulations show that the hamming window is more efficient than the rectangular and triangular windows for obtaining a more consistent beam. In the second set of simulations, reflections are mapped with respect to the depth from which these reflections are generated. It demonstrates that the solid and water media allow for the attainment of echoes from deeper regions as compared to the air medium. Matlab is used as the simulation framework.
基金funded by a national grant of the Romanian Research Ministry-PNRR 10892024-2026(PNRR/2022/C9/MCID/18,Contract No.760278/26.03.2024)an international grant of the European Commission-Horizon Europe Framework Network,HORIZON-TMA-MSCA-DN(Proposal Number 101227725-“Advancing in the CHallenge of Improving Lymphoma and LEukemia Survival-ACHILLES”)a bilateral collaboration grant between Romania and Moldova(PN-IV-P8-8.3-ROMD-2023-0036).
文摘Immune thrombocytopenic purpura(ITP)is an autoimmune disorder characterized by autoantibody-mediated platelet destruction and impaired platelet production,leading to bleeding risk at platelet counts<100×10^(9)/L.In adults,ITP often becomes chronic and recurrent,necessitating multiple lines of therapy,including corticosteroids,intravenous immunoglobulins,splenectomy,rituximab,thrombopoietin receptor agonists(TPO-RAs),and fostamatinib.Yet a subset of patients remains relapsed/refractory(r/r),with residual autoantibody-producing plasma cells driving persistent disease.Standard immunosuppression,as is the case of rituximab,targets CD20+B lymphocytes and might spare long-lived plasma cells(LLPCs).Autoantibodies persist if LLPCs survive.Daratumumab binds CD38 expressed on plasmablasts and plasma cells,including LLPCs;and depletes them efficiently,removing autoantibody sources.
文摘Introduction:Coronavirus disease 2019(COVID-19)may be associated with various skin manifestations.Among them,figurate erythema(FE)is rare;only a few clinical reports have been published.Herein,we reported an unusual concentric FE lesions and their immunohistochemical profile in a patient with COVID-19.Case presentation:A 52-year-old woman was diagnosed with COVID-19.One month later,she developed asymptomatic annular erythematous concentric ring lesions on her inner right thigh.The margin of every ring increased in coloration,and the lesions then completely resolved in 2 weeks.A biopsy revealed vasculitis of small vessels,an increase in the fluorescence intensity of CD3 and CD45,and negativity for COVID-19 RNA.Discussion:The results showed an unusual FE that has a clinical mixed type between erythema annulare centrifugum and erythema gyratum repens;the physiopathological mechanism in the FE due to COVID-19 is unknown;one theory involves rapid viral passage into the cutaneous vascular system that triggers an immune and inflammatory response.Although the results exhibited a negative COVID-19 RNA in the tissue,the CD3^(+)/CD45^(+)lymphocyte infiltration could explain the clinical pattern as a direct inflammatory response in the small vessel or as a delayed immune response.Conclusion:Our findings suggest an immunohistochemical small vessel vasculitis pattern with an unusual clinical FE that differs from other types of COVID-19-associated FE or erythema reported previously.
基金Basic Science Research Program(2020R1A2B03002517 and 2021R1A2C1094274)through the National Research Foundation of Korea and the KRIBB Research Initiative Program(KGM 5242221)which are funded by the Ministry of Science,ICT and Future Planning,Republic of Korea.
文摘The biosynthesis of host lipids and/or lipid droplets(LDs)has been studied extensively as a putative therapeutic target in diverse viral infections.However,directly targeting the LD lipolytic catabolism in virus-infected cells has not been widely investigated.Here,we show the linkage of the LD-associated lipase activation to the breakdown of LDs for the generation of free fatty acids(FFAs)at the late stage of diverse RNA viral infections,which represents a broad-spectrum antiviral target.Dysfunction of membrane transporter systems due to virus-induced cell injury results in intracellular malnutrition at the late stage of infection,thereby making the virus more dependent on the FFAs generated from LD storage for viral morphogenesis and as a source of energy.The replication of SARS-CoV-2 and influenza A virus(IAV),which is suppressed by the treatment with LD-associated lipases inhibitors,is rescued by supplementation with FFAs.The administration of lipase inhibitors,either individually or in a combination with virus-targeting drugs,protects mice from lethal IAV infection and mitigates severe lung lesions in SARS-CoV-2-infected hamsters.Moreover,the lipase inhibitors significantly reduce proinflammatory cytokine levels in the lungs of SARS-CoV-2-and IAV-challenged animals,a cause of a cytokine storm important for the critical infection or mortality of COVID-19 and IAV patients.In conclusion,the results reveal that lipase-mediated intracellular LD lipolysis is commonly exploited to facilitate RNA virus replication and furthermore suggest that pharmacological inhibitors of LD-associated lipases could be used to curb current COVID-19-and future pandemic outbreaks of potentially troublesome RNA virus infection in humans.
