BACKGROUND The presence of hepatitis C virus(HCV)RNA in liver tissue or peripheral blood mononuclear cells with no identified virus genome in the serum has been reported worldwide among patients with either normal or ...BACKGROUND The presence of hepatitis C virus(HCV)RNA in liver tissue or peripheral blood mononuclear cells with no identified virus genome in the serum has been reported worldwide among patients with either normal or elevated serum liver enzymes.The characterization of occult HCV infection(OCI)epidemiology in the Middle East and Eastern Mediterranean(M and E)countries,a region with the highest incidence and prevalence rates of HCV infection in the world,would be effective for more appropriate control of the infection.AIM To estimate the pooled prevalence of OCI in M and E countries using a systematic review and meta-analysis.METHODS A systematic literature search was performed using international,regional and local electronic databases.Some conference proceedings and references from bibliographies were also reviewed manually.The search was carried out during May and June 2020.Original observational surveys were considered if they assessed the prevalence of OCI among the population of M and E countries by examination of HCV nucleic acid in peripheral blood mononuclear cells in at least 30 cases selected by random or non-random sampling methods.The meta-analysis was performed using Comprehensive Meta-analysis software based on heterogeneity assessed by Cochran’s Q test and I-square statistics.Data were considered statistically significant at a P value<0.05.RESULTS A total of 116 non-duplicated citations were found in electronic sources and grey literature.A total of 51 non-overlapping original surveys were appraised,of which 37 met the inclusion criteria and were included in the analysis.Data were available from 5 of 26 countries including Egypt,Iran,Pakistan,Saudi Arabia,and Turkey.The overall prevalence rate of OCI was estimated at 10.04%(95%CI:7.66%-13.05%).The lowest OCI rate was observed among healthy subjects(4.79%,95%CI:2.86%-7.93%).The higher rates were estimated for patients suffering from chronic liver diseases(12.04%,95%CI:5.87%-23.10%),and multi-transfused patients(8.71%,95%CI:6.05%-12.39%).Subgroup analysis indicated that the OCI rates were probably not associated with the studied subpopulations,country,year of study,the detection method of HCV RNA,sample size,patients’HCV serostatus,and sex(all P>0.05).Meta-regression analyses showed no significant time trends in OCI rates among different groups.CONCLUSION This review estimated high rates of OCI prevalence in M and E countries,especially among multi-transfused patients as well as patients with chronic liver diseases.展开更多
Objectives:To evaluate clinical features,treatment strategies,and outcomes of pleural empyema for children who were treated at referral pediatric hospitals in 8 provinces of Iran.Methods:In this retrospective,multicen...Objectives:To evaluate clinical features,treatment strategies,and outcomes of pleural empyema for children who were treated at referral pediatric hospitals in 8 provinces of Iran.Methods:In this retrospective,multicenter cross sectional study,we retrospectively retrieved patients'data from 8 teaching hospitals during 2010 and 2017.A questionnaire was applied and filled,and all data were statistically and descriptively analyzed.Results:In total,191 children(109 males and 82 females)were included.Their mean age was 4.95 years and ranged from 11 months to 16 years.The majority of cases(45.1%)were 1-4 years old.Fever(70.3%),cough(65.6%),tachypnea(53.1%),chest pain(14.6%),and abdominal pain(12%)were the most common manifestations at admission.The mean length of admission in hospital was 16.4 d.Consequently,27 patients(14.1%)were admitted into the pediatric intensive unit because of severe illness,and 15 patients(7.9%)died.Logistic regression analysis showed that younger age(less than 12 months)and presence of underlying diseases(such as cardiovascular disease,immune deficiencies,malignancies,and neuro-developmental delay)significantly increased the mortality rate of patients with pleural empyema(P=0.004 and P=0.001,respectively).Conclusions:Pleural empyema children of younger age and with underlying diseases are at higher risks of death.In addition,guidelines for treating pleural empyema should be developed.展开更多
Pharmaceuticals and personal care products(PPCPs)have been considered as potential contributors to thyroid nodule(TN)and abnormal thyroid homeostasis,but epidemiological evidence is scarce.A total of 1261 individuals ...Pharmaceuticals and personal care products(PPCPs)have been considered as potential contributors to thyroid nodule(TN)and abnormal thyroid homeostasis,but epidemiological evidence is scarce.A total of 1261 individuals comprised of 367 TN patients and 895 controls were recruited from Sichuan,China.The urinary concentrations of fourteen PPCPs were measured.Five thyroid hormones(THs)in serum were determined as indicators of thyroid homeostasis,including thyroid-stimulating hormone,triiodothyronine(T3),thyroxine(T4),free-T3 and free-T4.Serum levels of thyroglobulin antibody(TGAb)and thyroperoxidase antibody(TPOAb)were quantified to identify individual thyroid antibody(TA)statuses.TN patients exhibited higher propyl-paraben(PrP)(median:1.30μg/g Cr)level than controls(0.64μg/g Cr).PrP were significantly associated with TN risk with ORs of 1.060(95%CI:1.002,1.122).The relationship of methyl-paraben with TN risk was nonlinear(p=0.049).PPCP exposurewas significantwith TN risk only in females and TA positive(TPOAb or TGAb)groups,indicating that PPCP susceptibility to TN differs by sex and TA status.Linear regression models showed ethyl-paraben was significantly negatively associated with T4(β:-0.005,95%CI:-0.011,-0.002)and T3(β:-0.007,95%CI:-0.015,-0.002),and positively associated with TPOAb(β:0.059,95%CI:0.000,0.119),suggesting that certain PPCP exposure could affect thyroid homeostasis and autoimmunity.The effects of PPCP exposure on TH and TA levels presented sex-specific.Our findings suggest that PPCP exposure increases TN risk and affects thyroid homeostasis,exhibiting sex and antibody status dependence.展开更多
BACKGROUND Early diagnosis of hepatocellular carcinoma may help to ensure that patients have a chance for long-term survival;however,currently available biomarkers lack sensitivity and specificity.AIM To characterize ...BACKGROUND Early diagnosis of hepatocellular carcinoma may help to ensure that patients have a chance for long-term survival;however,currently available biomarkers lack sensitivity and specificity.AIM To characterize the serum metabolome of hepatocellular carcinoma in order to develop a new metabolomics diagnostic model and identifying novel biomarkers for screening hepatocellular carcinoma based on the pattern recognition method.METHODS Ultra-performance liquid chromatography-mass spectroscopy was used to characterize the serum metabolome of hepatocellular carcinoma(n=30)and cirrhosis(n=29)patients,followed by sequential feature selection combined with linear discriminant analysis to process the multivariate data.RESULTS The concentrations of most metabolites,including proline,were lower in patients with hepatocellular carcinoma,whereas the hydroxypurine levels were higher in these patients.As ordinary analysis models failed to discriminate hepatocellular carcinoma from cirrhosis,pattern recognition analysis was used to establish a pattern recognition model that included hydroxypurine and proline.The leaveone-out cross-validation accuracy and area under the receiver operating characteristic curve analysis were 95.00%and 0.90[95%Confidence Interval(CI):0.81-0.99]for the training set,respectively,and 78.95%and 0.84(95%CI:0.67-1.00)for the validation set,respectively.In contrast,forα-fetoprotein,the accuracy and area under the receiver operating characteristic curve were 65.00%and 0.69(95%CI:0.52-0.86)for the training set,respectively,and 68.42%and 0.68(95%CI:0.41-0.94)for the validation set,respectively.The Z test revealed that the area under the curve of the linear discriminant analysis model was significantly higher than the area under the curve ofα-fetoprotein(P<0.05)in both the training and validation sets.CONCLUSION Hydroxypurine and proline might be novel biomarkers for hepatocellular carcinoma,and this disease could be diagnosed by the metabolomics model based on pattern recognition.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
BACKGROUND The onset symptoms of people infected by Chlamydia psittaci can mimic the coronavirus disease 2019(COVID-19).However,the differences in laboratory tests and imaging features between psittacosis and COVID-19...BACKGROUND The onset symptoms of people infected by Chlamydia psittaci can mimic the coronavirus disease 2019(COVID-19).However,the differences in laboratory tests and imaging features between psittacosis and COVID-19 remain unknown.AIM To better understand the two diseases and then make an early diagnosis and treatment.METHODS Six patients from two institutions confirmed as psittacosis by high-throughput genetic testing and 31 patients confirmed as COVID-19 were retrospectively included.The epidemiology,clinical characteristics,laboratory tests and computed tomography(CT)imaging features were collected and compared between the two groups.The follow-up CT imaging findings of patients with psittacosis were also investigated.RESULTS The white blood cell count(WBC),neutrophil count and calcium were more likely to be decreased in patients with COVID-19 but were increased in patients with psittacosis(all P=0.000).Lymphocyte count and platelet count were higher in patients with psittacosis than in those with COVID-19(P=0.044,P=0.035,respectively).Lesions in patients with psittacosis were more likely to be unilateral(P=0.001),involve fewer lung lobes(P=0.006)and have pleural effusions(P=0.002).Vascular enlargement was more common in patients with COVID-19(P=0.003).Consolidation in lung CT images was absorbed in all 6 patients.CONCLUSION Psittacosis has the potential for human-to-human transmission.Patients with psittacosis present increased WBC count and neutrophil count and have specific CT imaging findings,including unilateral distribution,less involvement of lung lobes and pleural effusions,which might help us to differentiate it from COVID-19.展开更多
Chronic hepatitis B, as a global health problem, is a disease that begins in the prenatal period and its complications gradually become clear later in life. About 5% of women worldwide are carriers of chronic hepatiti...Chronic hepatitis B, as a global health problem, is a disease that begins in the prenatal period and its complications gradually become clear later in life. About 5% of women worldwide are carriers of chronic hepatitis B virus(HBV). The most common method of transmission of HBV around the world is from mother to infant. This article aims to review the unique challenges of hepatitis B in pregnancy. Data for this review were collected from our previous studiesand experiences plus various data banks, such as Pub Med, EMBASE, ISI Web of science, Scopus, Google Scholar and Iranian databases. A comprehensive search was performed using the combinations of the keywords to review relevant literature and higher education journals. All published data up to February 2014 have been included in this review. This article addresses several interesting aspects. First, hepatitis B in pregnancy can vary regarding prevalence, virus behavior, prenatal transmission and outcome of the pregnancy. Second, the women of reproductive age with chronic HBV remain a major source for continued spread of the virus. Finally, pregnant women need screening in prenatal care to enable early intervention when necessary.展开更多
Objective: To determine the antibiotic resistance patterns of the Acinetobacter(A.) baumannii complex isolates that cause the confirmed infection. Methods: The present descriptive study was performed from March 2016 t...Objective: To determine the antibiotic resistance patterns of the Acinetobacter(A.) baumannii complex isolates that cause the confirmed infection. Methods: The present descriptive study was performed from March 2016 to March 2018 in three referral hospitals in Isfahan, Iran. All A. baumannii complex strains isolated from different clinical samples were identified by conventional phenotypic methods and antibiotic susceptibility pattern was detected. After the clinical investigation, contaminated samples were excluded and the source(hospital/community) and site of the infection were determined. Data on antibiotic susceptibility testing were extracted from WHONET software and analysis was done with SPSS.Results: From 254 patients who had confirmed A. baumannii complex infection, 158(62.20%) cases were male, 27(10.63%) were less than 20 years old, 172(67.72%) had healthcare-associated infections and 96(37.79%) were admitted in intensive care units. The most frequent infection was bloodstream infections(111, 43.70%). Our results showed that most of the isolates were resistant to most of the antibiotics(more than 75.00%) and a lower rate of non-susceptibility was observed against minocycline(20, 44.44%) and colistin(0%). The rate of multidrug-resistant isolates was 88.97%. There was no significant difference between resistance of A. baumannii complex isolates according to age. However, the resistance to amikacin and minocycline and the rate of multidrug resistance(MDR) were significantly different between males and females. In patients with healthcare associated infection(HAI), MDR isolates were significantly different regarding admission in ICU ward. Resistance to levofloxacin and ciprofloxacin were lower in isolates from patients with bloodstream infections in comparison to other diagnoses.Conclusions: In our study, a high level of antibiotic resistance was detected in both community-acquired and healthcare-associated A. baumannii complex infections. Appropriate antibiotic prescription in a clinical setting is an essential need for the control and prevention of A. baumannii resistant infections.展开更多
The gene encoding urease subunit A (ureA) of Helicobacter pylori (H.pylori) was cloned from H.pylori isolate by polymerase chain reaction (PCR). Sterile distilled water instead of DNA served as negative control. The n...The gene encoding urease subunit A (ureA) of Helicobacter pylori (H.pylori) was cloned from H.pylori isolate by polymerase chain reaction (PCR). Sterile distilled water instead of DNA served as negative control. The nucleotide sequence of the amplified product was determined. Homologous analysis of the ureA against that reported by Clayton CL and the GenBank and SwissProt databases were performed with the BLAST program at the Genome Net through the Internet. 0.8 kb PCR product was amplified from all H.pylori clinical isolators. The nucleotide sequence of the ureA was determined. The nucleotide sequence of the ureA began with ATG as the initiation codon and terminated in TAA as stop codon. The coding regions had a 44 % G+C content. The DNA sequence was 98 % homologous to that reported by Clayton CL (688 out of 702 residues were identical). The derived amino acid sequences of the ureA were 99 % homologous to that reported by Clayton CL (232 out of 234 residues were identical). The nucleotide sequence and the predicted protein showed significant homology to ureA of H.pylori in the NCBI Entrez database.展开更多
HIV-associated neurocognitive disorders (HAND) are chronic complications of HIV infection in the central nervous system. Clinical presentations include asymptomatic neurocognitive impairment (ANI), mild neurocognitive...HIV-associated neurocognitive disorders (HAND) are chronic complications of HIV infection in the central nervous system. Clinical presentations include asymptomatic neurocognitive impairment (ANI), mild neurocognitive impairment (MND), and HIV-associated dementia (HAD). In the era of combination antiretroviral therapy (cART), the prevalence of HAD has significantly decreased, but the rates of ANI and MND have increased, impairing patients’ daily functioning, medical adherence, employment, driving abilities, risk of HIV transmission, overall quality of life, and posing challenges to society, economy, families, and public health. This article reviews the latest research findings regarding the pathogenesis, clinical diagnosis and treatment, neuroimaging, and neuropsychological assessment of HAND, aiming to provide insights into the prevention and management of HAND.展开更多
Objective:To assess the effects of moxibustion on immune reconstitution inflammatory syndrome(IRIS)in patients with acquired immune deficiency syndrome(AIDS)by tracking T-cell subsets over a 48-week prospective cohort...Objective:To assess the effects of moxibustion on immune reconstitution inflammatory syndrome(IRIS)in patients with acquired immune deficiency syndrome(AIDS)by tracking T-cell subsets over a 48-week prospective cohort study.Methods:Patients with AIDS who had low viral loads and weakened immune systems were divided into a moxibustion group and a non-moxibustion group.The non-moxibustion group received standard western treatment,including 48 weeks of antiretroviral therapy(ART).The moxibustion group received ART combined with moxibusion therapy,administered three times weekly.Each treatment lasted 10 weeks,with four courses completed over 48 weeks,separated by 2-week breaks.At different time points,plasma levels of CD4^(+),CD8^(+),CD45RAt,CD45RO^(+),CD4^(+)CD28^(+),CD8^(+)CD38^(+),and CD4^(+)CD38^(+)were compared between the two groups.Results:A total of 200 eligible patients were included and divided into two groups,with 100 in the non-moxibustion group and 100 in the moxibustion group.At Week 24,the CD4^(+)T cell count was(180.71±79.62)cells/μL in the non-moxibustion group and(218.22±82.02)cells/μL in the moxibustion group.By Week 36,the counts were(204.83±96.78)cells/μuL and(239.35±81.90)cells/μL,respectively.At Weeks 24 and 48,the CD8^(+)T cell and CD45RO^(+)counts were higher in the moxibustion group than in the non-moxibustion group(P<0.05).By Week 48,the CD45RA^(+)count was also higher in the moxibustion group(P<0.05).At Week 24,the CD4^(+)CD25^(+)count was lower in the moxibustion group than in the non-moxibustion group(P<0.05).展开更多
Summary: The vacuolated effect of Helicobacter (H. pylori) and its relationship to vacuolated cytotoxin antigen (VacA) were investigated by the method of cytotoxic test and SDS-pobyacrylamide gel electrophoresis (SDS-...Summary: The vacuolated effect of Helicobacter (H. pylori) and its relationship to vacuolated cytotoxin antigen (VacA) were investigated by the method of cytotoxic test and SDS-pobyacrylamide gel electrophoresis (SDS-PAGE). Of the 62 clinical isolates, the broth culture filter (BCF) of 43 strains caused the Vero cell intracytoplasmically vacuolated. H. pylori strains were divided into H. pylori (Toxin +) group with vacuolated effect and H. pylori (Toxin -) group without vacuolated effect. The analysis of the BCF of H. pylori (Toxin +) and that of H. pylori (Toxin -) was studied by SDS-PAGE and Scan reader. A kind of protein with 87 ku molecular weight was recognized in the BCF of 30.23 % (13/43) H. pylori (Toxin +) strains but in none of that of H. pylori (Toxin -) strains, the difference was statistically significant (P<0.05). There was a significant and concordant relationship between OD of the protein band with 87 ku molecular weight and titer of vacuolated activity of H. pylori(Toxin +) (r=0.67 and P<0.05 by linear regression analysis). H. pylori strains were divided into H. pylori (Toxin +) group with vacuolated effect and H. pylori (Toxin -) group without vacuolated effect. The vacuolated effect of H. pylori (Toxin +) was caused by the protein with 87 ku molecular weight (VacA)展开更多
Objective: To estimate the frequency of pneumococcal meningitis among patients with bacterial meningitis in Iran. Methods: PubMed, Embase, Web of Science and Scientific Information Database (www. sid.ir) were searched...Objective: To estimate the frequency of pneumococcal meningitis among patients with bacterial meningitis in Iran. Methods: PubMed, Embase, Web of Science and Scientific Information Database (www. sid.ir) were searched from 2000 to 2016 to identify studies on the frequency or prevalence of pneumococcal meningitis in Iran. Stata 14.0 (StataCorp, College Station, Texas, USA) was used to analyze the data. Results: Of the 131 records identified from the databases, 21 studies fulfilled the eligibility criteria. The analyses showed that 25.0% (95% CI: 19.0-32.0;I2=71%) of the confirmed bacterial meningitis (including children and adults) cases were caused by pneumococcus. Conclusions: The large fraction of meningitis cases caused by pneumococcus demonstrates that pneumococcal meningitis is a major public health problem in Iran, and the introduction of pneumococcal vaccines merits further attention from health authorities.展开更多
Objective To evaluate the performance for three commercial hepatitis C virus(HCV) core antigen assays in HCV infection screening,and to provide clues for further improving the sensitivity and specificity of the assays...Objective To evaluate the performance for three commercial hepatitis C virus(HCV) core antigen assays in HCV infection screening,and to provide clues for further improving the sensitivity and specificity of the assays.Methods Key performance indicators including the lower limit of detection(LOD),diagnostic sensitivity.展开更多
Background:Despite progress in therapeutic strategies,treatment failure in hepatocellular carcinoma(HCC)remains a major challenge,resulting in low survival rates.The presence of bacteria and the host’s immune respons...Background:Despite progress in therapeutic strategies,treatment failure in hepatocellular carcinoma(HCC)remains a major challenge,resulting in low survival rates.The presence of bacteria and the host’s immune response to bacteria can influence the pathogenesis and progression of HCC.We developed a risk model based on bacterial response-related genes(BRGs)using gene sets from molecular signature databases to identify new markers for predicting HCC outcomes and categorizing patients into different risk groups.Methods:The data from the Cancer Genome Atlas(TCGA)portal was retrieved,and differentially expressed BRGs were identified.Uni-and multivariate Cox regression and least absolute shrinkage and selection operator(LASSO)LASSO analyses were executed to develop the prognostic risk model.Key contributor to the prognostic model was identified,and the results were tested by using experimental assays in HCC cell lines.Results:Multivariate analysis demonstrated an independent prognostic factor of 12-BRG signature in HCC patients.The low-risk group had better overall survival with significantly lower tumor mutation burden(TMB).The risk scores were negatively correlated with the presence of tumor-infiltrating immune cells.In an effort to find the key contributor of the 12-BRG signature,we found polo like kinase1(PLK1)had the best accuracy with 1-,3-,and 5-year AUC of 0.72,0.66,and 0.65,respectively.Both PLK1 inhibitor Volasertib and the knockdown of the PLK1 gene resulted in diminished viability in HCC cell lines.The combination of PLK1 inhibition with low-dose chemotherapy exhibited an amplified effect of the treatment.Conclusion:To date,there have been no reports of BRG biomarkers in HCC,and this study represents for the first time that a 12-BRG signature has the potential to predict the survival of HCC.展开更多
Background： Klebsiellapneumoniae carbapenemase （KPC）-producing K. pneumoniae bacteria, which cause serious disease outbreaks worldwide, was rarely detected in Xiangya Hospital, prior to an outbreak that occurred fr...Background： Klebsiellapneumoniae carbapenemase （KPC）-producing K. pneumoniae bacteria, which cause serious disease outbreaks worldwide, was rarely detected in Xiangya Hospital, prior to an outbreak that occurred from August 4, 2014, to March 17, 2015. The aim of this study was to analyze the epidemiology and molecular characteristics of the K. pneumoniae strains isolated during the outbreak. Methods： Nonduplicate carbapenem-resistant K. pneumoniae isolates were screened for blanc,＂ and multiple other resistance determinants using polymerase chain reaction. Subsequent studies included pulsed-field gel electrophoresis （PFGE）, multilocus sequence typing, analysis of plasmids, and genetic organization ofblaKPC-2 locus. Results： Seventeen blaKPC-2-positive K. pneumoniae were identified. A wide range of resistant determinants was detected. Most isolates （88.2%） coharbored blaKPC-2 and rmtB in addition to other resistance genes, including biaSHV-1, blaTEM-1, and aac（3）-lla. The blaKPC-2 and rmtB genes were located on the conjugative IncFIB-type plasmid. Genetic organization of blaKPC-2 locus in most strains was consistent with that of the plasmid pKP048. Four types （A l, A2, A3, and B） were detected by PFGE, and Type A1, an ST11, was the predominant PFGE type. A novel K. pneumoniae sequence type （ST1883） related to STI 1 was discovered. Conclusions： These isolates in our study appeared to be clonal and STI 1 K. pneumoniae was the predominant clone attributed to the outbreak. Coharbing of blaKPC-2 and rmtB, which were located on a transferable plasmid, in clinical K. pneumoniae isolates may lead to the emergence of a new pattern of drug resistance.展开更多
Objective To summarize the clinical features and the Chinese medicine(CM)syndrome characteristics of the Coronavirus Disease 2019(COVID-19)caused by Omicron variant in Zhuhai,and explore CM diagnosis and treatment str...Objective To summarize the clinical features and the Chinese medicine(CM)syndrome characteristics of the Coronavirus Disease 2019(COVID-19)caused by Omicron variant in Zhuhai,and explore CM diagnosis and treatment strategies for the disease.展开更多
Background:Even with long-term complete suppression of the virus through antiretroviral therapy(ART),people infected with HIV cannot attain optimal immune reconstitution.This phenomenon is called immune reconstitution...Background:Even with long-term complete suppression of the virus through antiretroviral therapy(ART),people infected with HIV cannot attain optimal immune reconstitution.This phenomenon is called immune reconstitution deficiency,there are no effective therapeutic interventions for immune reconstitution deficiency in modern medicine.Objective:To evaluate the efficacy and safety of ART with Shenling Guben Granules Traditional Chinese medicine in boosting immunological reconstitution compared with ART alone.Methods:This was a randomized,double-blind,placebo-controlled,multicenter clinical trial evaluating the efficacy and safety of ART combined with Chinese medicine.The individuals aged 18–65 years with poor immune reconstitution following ART were included in this trial.The primary outcome was a change in the absolute value of CD4^(+)T lymphocytes after 72 weeks of combined ART and Chinese medicine administration.Secondary outcomes included changes in CD4^(+)T lymphocyte functional subpopulations,activated T lymphocyte subpopulations,CD4^(+)T lymphocyte proliferation,and T lymphocyte apoptosis from baseline to after 72 weeks.We also evaluated efficacy at 24-and 48-week intervals to better understand the dynamics of the trial drug’s efficacy.Results:There was a significant increase in CD4^(+)cell counts in groups treated with the Shenling Guben Granules after 24,48,and 72 weeks of treatment(P<0.05),and the difference in CD4^(+)cell counts at 24 weeks of treatment was statistically significant(P=0.010).After 48 and 72 weeks of therapy,the CD4^(+)CD38^(+)cell counts in the Shenling Guben Granules group were significantly higher than in the control group(P<0.05).In the subgroup analysis of CD4^(+)cell counts≥200 cells/mm^(3),the CD4^(+)cell counts in the treatment group were higher than the control group after treatment for 24,48,and 72 weeks(P<0.05).Discussion:CD4 cell counts in HIV/AIDS patients with immunological reconstitution insufficiency can be improved to a certain extent using Shenling Guben Granules.The greater the CD4 cell count at the start,the better the therapy response.Furthermore,Shenling Guben Granules have the efficacy and safety to prevent aberrant immunological activation.A large sample size,long-term follow-up,and multiple efficacy indicators were employed to assess the therapy’s safety.Our findings will lead to new therapeutic alternatives for HIV/AIDS patients suffering from immune reconstitution deficiency.Clinical Trial Registry:Name of the registry:Sundy on promote the reconstruction of Inadequate responders in HIV/AIDS patients after combined antiretroviral therapy by Shen Ling Gu Ben Granules;Chictr.org.cn Identifier:ChiCTR1800015290,registered on March 21,2018(http://www.chictr.org.cn/registry.aspx).展开更多
The creation of ex vivo human liver models has long been a critical objective in academic,clinical,and phar-maceutical research,particularly for drug development,where accurate evaluation of hepatic metabolic dy-namic...The creation of ex vivo human liver models has long been a critical objective in academic,clinical,and phar-maceutical research,particularly for drug development,where accurate evaluation of hepatic metabolic dy-namics is crucial.We have developed a bioengineered,perfused,organ-level human liver model that accurately replicates key liver functions,including metabolic activities,and protein synthesis,thus addressing some of the limitations associated with traditional liver monolayers,organoids,and matrix-embedded liver cells.Our approach utilizes liver-specific biomatrix scaffolds,prepared using an innovative protocol and fortified with matrix components that facilitate cellular interactions.These scaffolds,when seeded with human fetal liver cells or co-seeded with liver parenchymal and endothelial cell lines,enable the formation of three-dimensional(3D)human livers with enhanced cellular organization.The“recellularized tissue-engineered livers”(RCLs)have undergone various analyses,demonstrating the capability for establishing liver microenvironments ex vivo.Within 7-14 days,the RCLs exhibit evidence of liver differentiation and metabolic capabilities,underscoring the potential for use in drug metabolism and toxicity studies.Although our study represents a significant step for-ward,we acknowledge the need for direct comparisons with existing models and further research to fully elucidate the spectrum of regenerative responses.The high drug-metabolizing enzyme activity of RCLs,as demonstrated in our study,provides a promising avenue for investigating drug-induced liver injury mechanisms,contributing to a more detailed understanding of early drug discovery processes.展开更多
文摘BACKGROUND The presence of hepatitis C virus(HCV)RNA in liver tissue or peripheral blood mononuclear cells with no identified virus genome in the serum has been reported worldwide among patients with either normal or elevated serum liver enzymes.The characterization of occult HCV infection(OCI)epidemiology in the Middle East and Eastern Mediterranean(M and E)countries,a region with the highest incidence and prevalence rates of HCV infection in the world,would be effective for more appropriate control of the infection.AIM To estimate the pooled prevalence of OCI in M and E countries using a systematic review and meta-analysis.METHODS A systematic literature search was performed using international,regional and local electronic databases.Some conference proceedings and references from bibliographies were also reviewed manually.The search was carried out during May and June 2020.Original observational surveys were considered if they assessed the prevalence of OCI among the population of M and E countries by examination of HCV nucleic acid in peripheral blood mononuclear cells in at least 30 cases selected by random or non-random sampling methods.The meta-analysis was performed using Comprehensive Meta-analysis software based on heterogeneity assessed by Cochran’s Q test and I-square statistics.Data were considered statistically significant at a P value<0.05.RESULTS A total of 116 non-duplicated citations were found in electronic sources and grey literature.A total of 51 non-overlapping original surveys were appraised,of which 37 met the inclusion criteria and were included in the analysis.Data were available from 5 of 26 countries including Egypt,Iran,Pakistan,Saudi Arabia,and Turkey.The overall prevalence rate of OCI was estimated at 10.04%(95%CI:7.66%-13.05%).The lowest OCI rate was observed among healthy subjects(4.79%,95%CI:2.86%-7.93%).The higher rates were estimated for patients suffering from chronic liver diseases(12.04%,95%CI:5.87%-23.10%),and multi-transfused patients(8.71%,95%CI:6.05%-12.39%).Subgroup analysis indicated that the OCI rates were probably not associated with the studied subpopulations,country,year of study,the detection method of HCV RNA,sample size,patients’HCV serostatus,and sex(all P>0.05).Meta-regression analyses showed no significant time trends in OCI rates among different groups.CONCLUSION This review estimated high rates of OCI prevalence in M and E countries,especially among multi-transfused patients as well as patients with chronic liver diseases.
基金This study was supported by eight educational hospitals in eight provinces of Iran.
文摘Objectives:To evaluate clinical features,treatment strategies,and outcomes of pleural empyema for children who were treated at referral pediatric hospitals in 8 provinces of Iran.Methods:In this retrospective,multicenter cross sectional study,we retrospectively retrieved patients'data from 8 teaching hospitals during 2010 and 2017.A questionnaire was applied and filled,and all data were statistically and descriptively analyzed.Results:In total,191 children(109 males and 82 females)were included.Their mean age was 4.95 years and ranged from 11 months to 16 years.The majority of cases(45.1%)were 1-4 years old.Fever(70.3%),cough(65.6%),tachypnea(53.1%),chest pain(14.6%),and abdominal pain(12%)were the most common manifestations at admission.The mean length of admission in hospital was 16.4 d.Consequently,27 patients(14.1%)were admitted into the pediatric intensive unit because of severe illness,and 15 patients(7.9%)died.Logistic regression analysis showed that younger age(less than 12 months)and presence of underlying diseases(such as cardiovascular disease,immune deficiencies,malignancies,and neuro-developmental delay)significantly increased the mortality rate of patients with pleural empyema(P=0.004 and P=0.001,respectively).Conclusions:Pleural empyema children of younger age and with underlying diseases are at higher risks of death.In addition,guidelines for treating pleural empyema should be developed.
基金supported by the National Natural Science Foundation of China(Nos.21976046 and 42177412)the Ministry of Education of China(No.B17025).
文摘Pharmaceuticals and personal care products(PPCPs)have been considered as potential contributors to thyroid nodule(TN)and abnormal thyroid homeostasis,but epidemiological evidence is scarce.A total of 1261 individuals comprised of 367 TN patients and 895 controls were recruited from Sichuan,China.The urinary concentrations of fourteen PPCPs were measured.Five thyroid hormones(THs)in serum were determined as indicators of thyroid homeostasis,including thyroid-stimulating hormone,triiodothyronine(T3),thyroxine(T4),free-T3 and free-T4.Serum levels of thyroglobulin antibody(TGAb)and thyroperoxidase antibody(TPOAb)were quantified to identify individual thyroid antibody(TA)statuses.TN patients exhibited higher propyl-paraben(PrP)(median:1.30μg/g Cr)level than controls(0.64μg/g Cr).PrP were significantly associated with TN risk with ORs of 1.060(95%CI:1.002,1.122).The relationship of methyl-paraben with TN risk was nonlinear(p=0.049).PPCP exposurewas significantwith TN risk only in females and TA positive(TPOAb or TGAb)groups,indicating that PPCP susceptibility to TN differs by sex and TA status.Linear regression models showed ethyl-paraben was significantly negatively associated with T4(β:-0.005,95%CI:-0.011,-0.002)and T3(β:-0.007,95%CI:-0.015,-0.002),and positively associated with TPOAb(β:0.059,95%CI:0.000,0.119),suggesting that certain PPCP exposure could affect thyroid homeostasis and autoimmunity.The effects of PPCP exposure on TH and TA levels presented sex-specific.Our findings suggest that PPCP exposure increases TN risk and affects thyroid homeostasis,exhibiting sex and antibody status dependence.
基金Supported by National Natural Science Foundation of China,No.81800472 and No.81670538the Science Foundation of Hunan Health Commission,No.B2019184.
文摘BACKGROUND Early diagnosis of hepatocellular carcinoma may help to ensure that patients have a chance for long-term survival;however,currently available biomarkers lack sensitivity and specificity.AIM To characterize the serum metabolome of hepatocellular carcinoma in order to develop a new metabolomics diagnostic model and identifying novel biomarkers for screening hepatocellular carcinoma based on the pattern recognition method.METHODS Ultra-performance liquid chromatography-mass spectroscopy was used to characterize the serum metabolome of hepatocellular carcinoma(n=30)and cirrhosis(n=29)patients,followed by sequential feature selection combined with linear discriminant analysis to process the multivariate data.RESULTS The concentrations of most metabolites,including proline,were lower in patients with hepatocellular carcinoma,whereas the hydroxypurine levels were higher in these patients.As ordinary analysis models failed to discriminate hepatocellular carcinoma from cirrhosis,pattern recognition analysis was used to establish a pattern recognition model that included hydroxypurine and proline.The leaveone-out cross-validation accuracy and area under the receiver operating characteristic curve analysis were 95.00%and 0.90[95%Confidence Interval(CI):0.81-0.99]for the training set,respectively,and 78.95%and 0.84(95%CI:0.67-1.00)for the validation set,respectively.In contrast,forα-fetoprotein,the accuracy and area under the receiver operating characteristic curve were 65.00%and 0.69(95%CI:0.52-0.86)for the training set,respectively,and 68.42%and 0.68(95%CI:0.41-0.94)for the validation set,respectively.The Z test revealed that the area under the curve of the linear discriminant analysis model was significantly higher than the area under the curve ofα-fetoprotein(P<0.05)in both the training and validation sets.CONCLUSION Hydroxypurine and proline might be novel biomarkers for hepatocellular carcinoma,and this disease could be diagnosed by the metabolomics model based on pattern recognition.
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.
基金the National Natural Science Foundation of China,No.82102157Hunan Provincial Natural Science Foundation of China,No.2021JJ40895+1 种基金the Science and Technology Innovation Program of Hunan Province,No.2020SK53423the Clinical Research Center For Medical Imaging in Hunan Province,No.2020SK4001.
文摘BACKGROUND The onset symptoms of people infected by Chlamydia psittaci can mimic the coronavirus disease 2019(COVID-19).However,the differences in laboratory tests and imaging features between psittacosis and COVID-19 remain unknown.AIM To better understand the two diseases and then make an early diagnosis and treatment.METHODS Six patients from two institutions confirmed as psittacosis by high-throughput genetic testing and 31 patients confirmed as COVID-19 were retrospectively included.The epidemiology,clinical characteristics,laboratory tests and computed tomography(CT)imaging features were collected and compared between the two groups.The follow-up CT imaging findings of patients with psittacosis were also investigated.RESULTS The white blood cell count(WBC),neutrophil count and calcium were more likely to be decreased in patients with COVID-19 but were increased in patients with psittacosis(all P=0.000).Lymphocyte count and platelet count were higher in patients with psittacosis than in those with COVID-19(P=0.044,P=0.035,respectively).Lesions in patients with psittacosis were more likely to be unilateral(P=0.001),involve fewer lung lobes(P=0.006)and have pleural effusions(P=0.002).Vascular enlargement was more common in patients with COVID-19(P=0.003).Consolidation in lung CT images was absorbed in all 6 patients.CONCLUSION Psittacosis has the potential for human-to-human transmission.Patients with psittacosis present increased WBC count and neutrophil count and have specific CT imaging findings,including unilateral distribution,less involvement of lung lobes and pleural effusions,which might help us to differentiate it from COVID-19.
文摘Chronic hepatitis B, as a global health problem, is a disease that begins in the prenatal period and its complications gradually become clear later in life. About 5% of women worldwide are carriers of chronic hepatitis B virus(HBV). The most common method of transmission of HBV around the world is from mother to infant. This article aims to review the unique challenges of hepatitis B in pregnancy. Data for this review were collected from our previous studiesand experiences plus various data banks, such as Pub Med, EMBASE, ISI Web of science, Scopus, Google Scholar and Iranian databases. A comprehensive search was performed using the combinations of the keywords to review relevant literature and higher education journals. All published data up to February 2014 have been included in this review. This article addresses several interesting aspects. First, hepatitis B in pregnancy can vary regarding prevalence, virus behavior, prenatal transmission and outcome of the pregnancy. Second, the women of reproductive age with chronic HBV remain a major source for continued spread of the virus. Finally, pregnant women need screening in prenatal care to enable early intervention when necessary.
文摘Objective: To determine the antibiotic resistance patterns of the Acinetobacter(A.) baumannii complex isolates that cause the confirmed infection. Methods: The present descriptive study was performed from March 2016 to March 2018 in three referral hospitals in Isfahan, Iran. All A. baumannii complex strains isolated from different clinical samples were identified by conventional phenotypic methods and antibiotic susceptibility pattern was detected. After the clinical investigation, contaminated samples were excluded and the source(hospital/community) and site of the infection were determined. Data on antibiotic susceptibility testing were extracted from WHONET software and analysis was done with SPSS.Results: From 254 patients who had confirmed A. baumannii complex infection, 158(62.20%) cases were male, 27(10.63%) were less than 20 years old, 172(67.72%) had healthcare-associated infections and 96(37.79%) were admitted in intensive care units. The most frequent infection was bloodstream infections(111, 43.70%). Our results showed that most of the isolates were resistant to most of the antibiotics(more than 75.00%) and a lower rate of non-susceptibility was observed against minocycline(20, 44.44%) and colistin(0%). The rate of multidrug-resistant isolates was 88.97%. There was no significant difference between resistance of A. baumannii complex isolates according to age. However, the resistance to amikacin and minocycline and the rate of multidrug resistance(MDR) were significantly different between males and females. In patients with healthcare associated infection(HAI), MDR isolates were significantly different regarding admission in ICU ward. Resistance to levofloxacin and ciprofloxacin were lower in isolates from patients with bloodstream infections in comparison to other diagnoses.Conclusions: In our study, a high level of antibiotic resistance was detected in both community-acquired and healthcare-associated A. baumannii complex infections. Appropriate antibiotic prescription in a clinical setting is an essential need for the control and prevention of A. baumannii resistant infections.
文摘The gene encoding urease subunit A (ureA) of Helicobacter pylori (H.pylori) was cloned from H.pylori isolate by polymerase chain reaction (PCR). Sterile distilled water instead of DNA served as negative control. The nucleotide sequence of the amplified product was determined. Homologous analysis of the ureA against that reported by Clayton CL and the GenBank and SwissProt databases were performed with the BLAST program at the Genome Net through the Internet. 0.8 kb PCR product was amplified from all H.pylori clinical isolators. The nucleotide sequence of the ureA was determined. The nucleotide sequence of the ureA began with ATG as the initiation codon and terminated in TAA as stop codon. The coding regions had a 44 % G+C content. The DNA sequence was 98 % homologous to that reported by Clayton CL (688 out of 702 residues were identical). The derived amino acid sequences of the ureA were 99 % homologous to that reported by Clayton CL (232 out of 234 residues were identical). The nucleotide sequence and the predicted protein showed significant homology to ureA of H.pylori in the NCBI Entrez database.
文摘HIV-associated neurocognitive disorders (HAND) are chronic complications of HIV infection in the central nervous system. Clinical presentations include asymptomatic neurocognitive impairment (ANI), mild neurocognitive impairment (MND), and HIV-associated dementia (HAD). In the era of combination antiretroviral therapy (cART), the prevalence of HAD has significantly decreased, but the rates of ANI and MND have increased, impairing patients’ daily functioning, medical adherence, employment, driving abilities, risk of HIV transmission, overall quality of life, and posing challenges to society, economy, families, and public health. This article reviews the latest research findings regarding the pathogenesis, clinical diagnosis and treatment, neuroimaging, and neuropsychological assessment of HAND, aiming to provide insights into the prevention and management of HAND.
基金Supported by National Major Science and Technology Projects:2017zX10205501National Public Welfare Industry Scientific Research Special:201507005+1 种基金2023 Beijing TCM Science and Technology Development Fund Project-Youth Project:BjzYQN-2023-05China Academy of Chinese Medical Sciences Outstanding Youth Program:ZZ15-YQ-048.
文摘Objective:To assess the effects of moxibustion on immune reconstitution inflammatory syndrome(IRIS)in patients with acquired immune deficiency syndrome(AIDS)by tracking T-cell subsets over a 48-week prospective cohort study.Methods:Patients with AIDS who had low viral loads and weakened immune systems were divided into a moxibustion group and a non-moxibustion group.The non-moxibustion group received standard western treatment,including 48 weeks of antiretroviral therapy(ART).The moxibustion group received ART combined with moxibusion therapy,administered three times weekly.Each treatment lasted 10 weeks,with four courses completed over 48 weeks,separated by 2-week breaks.At different time points,plasma levels of CD4^(+),CD8^(+),CD45RAt,CD45RO^(+),CD4^(+)CD28^(+),CD8^(+)CD38^(+),and CD4^(+)CD38^(+)were compared between the two groups.Results:A total of 200 eligible patients were included and divided into two groups,with 100 in the non-moxibustion group and 100 in the moxibustion group.At Week 24,the CD4^(+)T cell count was(180.71±79.62)cells/μL in the non-moxibustion group and(218.22±82.02)cells/μL in the moxibustion group.By Week 36,the counts were(204.83±96.78)cells/μuL and(239.35±81.90)cells/μL,respectively.At Weeks 24 and 48,the CD8^(+)T cell and CD45RO^(+)counts were higher in the moxibustion group than in the non-moxibustion group(P<0.05).By Week 48,the CD45RA^(+)count was also higher in the moxibustion group(P<0.05).At Week 24,the CD4^(+)CD25^(+)count was lower in the moxibustion group than in the non-moxibustion group(P<0.05).
基金This work was supported by a grant from National NaturalScience Foundation of China(No. 395 70 334 )
文摘Summary: The vacuolated effect of Helicobacter (H. pylori) and its relationship to vacuolated cytotoxin antigen (VacA) were investigated by the method of cytotoxic test and SDS-pobyacrylamide gel electrophoresis (SDS-PAGE). Of the 62 clinical isolates, the broth culture filter (BCF) of 43 strains caused the Vero cell intracytoplasmically vacuolated. H. pylori strains were divided into H. pylori (Toxin +) group with vacuolated effect and H. pylori (Toxin -) group without vacuolated effect. The analysis of the BCF of H. pylori (Toxin +) and that of H. pylori (Toxin -) was studied by SDS-PAGE and Scan reader. A kind of protein with 87 ku molecular weight was recognized in the BCF of 30.23 % (13/43) H. pylori (Toxin +) strains but in none of that of H. pylori (Toxin -) strains, the difference was statistically significant (P<0.05). There was a significant and concordant relationship between OD of the protein band with 87 ku molecular weight and titer of vacuolated activity of H. pylori(Toxin +) (r=0.67 and P<0.05 by linear regression analysis). H. pylori strains were divided into H. pylori (Toxin +) group with vacuolated effect and H. pylori (Toxin -) group without vacuolated effect. The vacuolated effect of H. pylori (Toxin +) was caused by the protein with 87 ku molecular weight (VacA)
文摘Objective: To estimate the frequency of pneumococcal meningitis among patients with bacterial meningitis in Iran. Methods: PubMed, Embase, Web of Science and Scientific Information Database (www. sid.ir) were searched from 2000 to 2016 to identify studies on the frequency or prevalence of pneumococcal meningitis in Iran. Stata 14.0 (StataCorp, College Station, Texas, USA) was used to analyze the data. Results: Of the 131 records identified from the databases, 21 studies fulfilled the eligibility criteria. The analyses showed that 25.0% (95% CI: 19.0-32.0;I2=71%) of the confirmed bacterial meningitis (including children and adults) cases were caused by pneumococcus. Conclusions: The large fraction of meningitis cases caused by pneumococcus demonstrates that pneumococcal meningitis is a major public health problem in Iran, and the introduction of pneumococcal vaccines merits further attention from health authorities.
文摘Objective To evaluate the performance for three commercial hepatitis C virus(HCV) core antigen assays in HCV infection screening,and to provide clues for further improving the sensitivity and specificity of the assays.Methods Key performance indicators including the lower limit of detection(LOD),diagnostic sensitivity.
文摘Background:Despite progress in therapeutic strategies,treatment failure in hepatocellular carcinoma(HCC)remains a major challenge,resulting in low survival rates.The presence of bacteria and the host’s immune response to bacteria can influence the pathogenesis and progression of HCC.We developed a risk model based on bacterial response-related genes(BRGs)using gene sets from molecular signature databases to identify new markers for predicting HCC outcomes and categorizing patients into different risk groups.Methods:The data from the Cancer Genome Atlas(TCGA)portal was retrieved,and differentially expressed BRGs were identified.Uni-and multivariate Cox regression and least absolute shrinkage and selection operator(LASSO)LASSO analyses were executed to develop the prognostic risk model.Key contributor to the prognostic model was identified,and the results were tested by using experimental assays in HCC cell lines.Results:Multivariate analysis demonstrated an independent prognostic factor of 12-BRG signature in HCC patients.The low-risk group had better overall survival with significantly lower tumor mutation burden(TMB).The risk scores were negatively correlated with the presence of tumor-infiltrating immune cells.In an effort to find the key contributor of the 12-BRG signature,we found polo like kinase1(PLK1)had the best accuracy with 1-,3-,and 5-year AUC of 0.72,0.66,and 0.65,respectively.Both PLK1 inhibitor Volasertib and the knockdown of the PLK1 gene resulted in diminished viability in HCC cell lines.The combination of PLK1 inhibition with low-dose chemotherapy exhibited an amplified effect of the treatment.Conclusion:To date,there have been no reports of BRG biomarkers in HCC,and this study represents for the first time that a 12-BRG signature has the potential to predict the survival of HCC.
基金grants from Hunan Development and Reform Investment from the Development and Reform Commission of the Hunan Province，the Natural Science Foundation of the Hunan Province
文摘Background： Klebsiellapneumoniae carbapenemase （KPC）-producing K. pneumoniae bacteria, which cause serious disease outbreaks worldwide, was rarely detected in Xiangya Hospital, prior to an outbreak that occurred from August 4, 2014, to March 17, 2015. The aim of this study was to analyze the epidemiology and molecular characteristics of the K. pneumoniae strains isolated during the outbreak. Methods： Nonduplicate carbapenem-resistant K. pneumoniae isolates were screened for blanc,＂ and multiple other resistance determinants using polymerase chain reaction. Subsequent studies included pulsed-field gel electrophoresis （PFGE）, multilocus sequence typing, analysis of plasmids, and genetic organization ofblaKPC-2 locus. Results： Seventeen blaKPC-2-positive K. pneumoniae were identified. A wide range of resistant determinants was detected. Most isolates （88.2%） coharbored blaKPC-2 and rmtB in addition to other resistance genes, including biaSHV-1, blaTEM-1, and aac（3）-lla. The blaKPC-2 and rmtB genes were located on the conjugative IncFIB-type plasmid. Genetic organization of blaKPC-2 locus in most strains was consistent with that of the plasmid pKP048. Four types （A l, A2, A3, and B） were detected by PFGE, and Type A1, an ST11, was the predominant PFGE type. A novel K. pneumoniae sequence type （ST1883） related to STI 1 was discovered. Conclusions： These isolates in our study appeared to be clonal and STI 1 K. pneumoniae was the predominant clone attributed to the outbreak. Coharbing of blaKPC-2 and rmtB, which were located on a transferable plasmid, in clinical K. pneumoniae isolates may lead to the emergence of a new pattern of drug resistance.
文摘Objective To summarize the clinical features and the Chinese medicine(CM)syndrome characteristics of the Coronavirus Disease 2019(COVID-19)caused by Omicron variant in Zhuhai,and explore CM diagnosis and treatment strategies for the disease.
基金Supported by the State Major Science&Technology Specific Projects(2017ZX10205501)National Nature Science Foundation of China(82174221).
文摘Background:Even with long-term complete suppression of the virus through antiretroviral therapy(ART),people infected with HIV cannot attain optimal immune reconstitution.This phenomenon is called immune reconstitution deficiency,there are no effective therapeutic interventions for immune reconstitution deficiency in modern medicine.Objective:To evaluate the efficacy and safety of ART with Shenling Guben Granules Traditional Chinese medicine in boosting immunological reconstitution compared with ART alone.Methods:This was a randomized,double-blind,placebo-controlled,multicenter clinical trial evaluating the efficacy and safety of ART combined with Chinese medicine.The individuals aged 18–65 years with poor immune reconstitution following ART were included in this trial.The primary outcome was a change in the absolute value of CD4^(+)T lymphocytes after 72 weeks of combined ART and Chinese medicine administration.Secondary outcomes included changes in CD4^(+)T lymphocyte functional subpopulations,activated T lymphocyte subpopulations,CD4^(+)T lymphocyte proliferation,and T lymphocyte apoptosis from baseline to after 72 weeks.We also evaluated efficacy at 24-and 48-week intervals to better understand the dynamics of the trial drug’s efficacy.Results:There was a significant increase in CD4^(+)cell counts in groups treated with the Shenling Guben Granules after 24,48,and 72 weeks of treatment(P<0.05),and the difference in CD4^(+)cell counts at 24 weeks of treatment was statistically significant(P=0.010).After 48 and 72 weeks of therapy,the CD4^(+)CD38^(+)cell counts in the Shenling Guben Granules group were significantly higher than in the control group(P<0.05).In the subgroup analysis of CD4^(+)cell counts≥200 cells/mm^(3),the CD4^(+)cell counts in the treatment group were higher than the control group after treatment for 24,48,and 72 weeks(P<0.05).Discussion:CD4 cell counts in HIV/AIDS patients with immunological reconstitution insufficiency can be improved to a certain extent using Shenling Guben Granules.The greater the CD4 cell count at the start,the better the therapy response.Furthermore,Shenling Guben Granules have the efficacy and safety to prevent aberrant immunological activation.A large sample size,long-term follow-up,and multiple efficacy indicators were employed to assess the therapy’s safety.Our findings will lead to new therapeutic alternatives for HIV/AIDS patients suffering from immune reconstitution deficiency.Clinical Trial Registry:Name of the registry:Sundy on promote the reconstruction of Inadequate responders in HIV/AIDS patients after combined antiretroviral therapy by Shen Ling Gu Ben Granules;Chictr.org.cn Identifier:ChiCTR1800015290,registered on March 21,2018(http://www.chictr.org.cn/registry.aspx).
基金Financial support Studies were funded in part by grants to Yunfang Wang,including National Key Research and Development Program of China(No.2022YFA1103400)National Natural Science Foundation of China(No.92168207)+1 种基金in part to Lola Reid at UNC.Those to Lola Reid included funds from Vesta Therapeutics(Bethesda,MD)that has merged now with PhoenixSongs Biologicals to form Vesta Biotherapeutics(Branford,CT).Praveen Sethupathy,PhD,was funded by an NIDDK/NIH grant(R00DK091318-02)supported in part by Dr.Sethupathy’s R00 grant and as well by a F31 fellowship.
文摘The creation of ex vivo human liver models has long been a critical objective in academic,clinical,and phar-maceutical research,particularly for drug development,where accurate evaluation of hepatic metabolic dy-namics is crucial.We have developed a bioengineered,perfused,organ-level human liver model that accurately replicates key liver functions,including metabolic activities,and protein synthesis,thus addressing some of the limitations associated with traditional liver monolayers,organoids,and matrix-embedded liver cells.Our approach utilizes liver-specific biomatrix scaffolds,prepared using an innovative protocol and fortified with matrix components that facilitate cellular interactions.These scaffolds,when seeded with human fetal liver cells or co-seeded with liver parenchymal and endothelial cell lines,enable the formation of three-dimensional(3D)human livers with enhanced cellular organization.The“recellularized tissue-engineered livers”(RCLs)have undergone various analyses,demonstrating the capability for establishing liver microenvironments ex vivo.Within 7-14 days,the RCLs exhibit evidence of liver differentiation and metabolic capabilities,underscoring the potential for use in drug metabolism and toxicity studies.Although our study represents a significant step for-ward,we acknowledge the need for direct comparisons with existing models and further research to fully elucidate the spectrum of regenerative responses.The high drug-metabolizing enzyme activity of RCLs,as demonstrated in our study,provides a promising avenue for investigating drug-induced liver injury mechanisms,contributing to a more detailed understanding of early drug discovery processes.
