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INTRODUCTION: Although cytologic examination of biliary stricture brushings obtained by endoscopic retrograde cholangiopancreatography is commonly used for diagnosing malignant biliary strictures (MBSs), it has low sensitivity. Several new brushes have capabilities that are still being debated. We have developed a novel brush working from conventional back-and-forth movement to rotation in situ (RIS) that may be more efficient for MBS sampling. We aimed to compare the MBS detection sensitivity of our RIS brush with that of the conventional brush. METHODS: In this multicenter prospective study, we enrolled patients who underwent endoscopic retrograde cholangiopancreatography for suspected MBSs involving biliary stricture brushings obtained using our RIS brush. The historical control group consisted of the 30-brushing arm of our previous randomized trial (patient inclusion, 2018-2020) that used the study design in the same centers and with the same endoscopists as were used in this study. The primary outcome was to compare the sensitivity and specificity of detecting MBSs by cytologic evaluation of biliary stricture brushings between the 2 groups. RESULTS: We enrolled 155 patients in the intent-to-treat analysis. Using the same number of brushing cycles, the RIS brush showed a higher sensitivity than the conventional brush (0.73 vs 0.56, P = 0.003). In per-protocol population, the sensitivity was also higher in the RIS brush group than in the conventional brush group (0.75 vs 0.57, P = 0.002). Multivariate analysis revealed that the RIS brush was the only predictive factor for MBS detection. No significant differences were observed in procedure-related complications between the 2 groups. DISCUSSION: The RIS brush was a promising tool for effective and safe MBS sampling and diagnosis. Further randomized studies are warranted to confirm our results (Chictr.org.cn, identifier: ChiCTR2100047270).
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Xenotropic and polytropic retrovirus receptor 1 (XPR1) is the only known transporter associated with Pi efflux in mammals, and its impact on tumor progression is gradually being revealed. However, the role of XPR1 in hepatocellular carcinoma (HCC) is unknown. A bioinformatics screen for the phosphate exporter XPR1 was performed in HCC patients. The expression of XPR1 in clinical specimens was analyzed using quantitative real-time PCR, Western blot analysis, and immunohistochemical assays. Knockdown of the phosphate exporter XPR1 was performed by shRNA transfection to investigate the cellular phenotype and phosphate-related cytotoxicity of the Huh7 and HLF cell lines. In vivo tests were conducted to investigate the tumorigenicity of HCC cells xenografted into immunocompromised mice after silencing XPR1. Compared with that in paracancerous tissue, XPR1 expression in HCC tissues was markedly upregulated. High XPR1 expression significantly correlated with poor patient survival. Silencing of XPR1 leads to decreased proliferation, migration, invasion, and colony formation in HCC cells. Mechanistically, knockdown of XPR1 causes an increase in intracellular phosphate levels; mitochondrial dysfunction characterized by reduced mitochondrial membrane potential and adenosine triphosphate levels; increased reactive oxygen species levels; abnormal mitochondrial morphology; and downregulation of key mitochondrial fusion, fission, and inner membrane genes. This ultimately results in mitochondria-dependent apoptosis. These findings reveal the prognostic value of XPR1 in HCC progression and, more importantly, suggest that XPR1 might be a potential therapeutic target.
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Cervical human papillomavirus (HPV) infection is believed to increase the risks of pregnancy failure and abortion, however, whether the uterine cavity HPV infection reduces pregnancy rate or increases miscarriage rate remains unclarified in infertile women undergoing assisted reproductive technology (ART) treatment. Therefore, we aimed to assess ART outcomes in the presence of intrauterine HPV. This was a hospital-based multicenter (five reproductive medicine centers) matched cohort study. This study involved 4153 infertile women undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection treatment in five reproductive medicine centers between October 2018 and 2020. The spent embryo transfer media sample with endometrium tissue were collected and performed with flow-through hybridization and gene chips to detect HPV DNA. According to basic characteristics, HPV-positive and negative patients were matched in a ratio of 1:4 by age, body mass index transfer timing, transfer type, and number of embryos transferred. The primary outcome was pregnancy and clinical miscarriage rates in the transfer cycle underwent HPV detection. 92 HPV-positive and 368 HPV-negative patients were screened and analyzed statistically. Univariate analysis showed uterine cavity HPV infection resulted in lower rates of ongoing pregnancy (31.5% vs. 44.6%; p = 0.023), implantation (32.3% vs. 43.1%; p = 0.026), biochemical pregnancy (47.8% vs. 62.5%; p = 0.010), and clinical pregnancy (40.2% vs. 54.3%; p = 0.015) compared with HPV negative group. The infertile female with positive HPV also had a slightly higher frequency of biochemical miscarriage (15.9% vs. 13.0%; p = 0.610) and clinical miscarriage (24.3% vs. 15.5%; p = 0.188). These findings suggest that HPV infection in the uterine cavity is a high risk for ART failure. HPV screening is recommended before ART treatment, which may be benefit to improving pregnancy outcome.
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Aborto Espontáneo , Infertilidad Femenina , Infecciones por Papillomavirus , Embarazo , Humanos , Masculino , Femenino , Infecciones por Papillomavirus/diagnóstico , Infertilidad Femenina/terapia , Virus del Papiloma Humano , Estudios de Cohortes , Semen , Transferencia de Embrión/métodos , Técnicas Reproductivas Asistidas , Fertilización In Vitro , Insuficiencia del TratamientoRESUMEN
AIM: We investigated the relationship between the complexity of the glucose time series index (CGI) during pregnancy and adverse pregnancy outcomes in women with gestational diabetes mellitus (GDM). MATERIALS AND METHODS: In this retrospective cohort study, 388 singleton pregnant women with GDM underwent continuous glucose monitoring (CGM) at a median of 26.86 gestational weeks. CGI was calculated using refined composite multiscale entropy based on CGM data. The participants were categorized into tertiles according to their baseline CGI (CGI <2.32, 2.32-3.10, ≥3.10). Logistic regression was used to assess the association between CGI and composite adverse outcomes or large for gestational age (LGA). The discrimination performance of CGI was estimated using receiver operating characteristic analysis. RESULTS: Of the 388 participants, 71 (18.3%) had LGA infants and 63 (16.2%) had composite adverse outcomes. After adjustments were made for confounders, compared with those with a high CGI (CGI ≥3.10), participants with a low CGI (CGI <2.32) had a higher risk of composite adverse outcomes (odds ratio: 12.10, 95% confidence interval: 4.41-33.18) and LGA (odds ratio: 12.68, 95% confidence interval: 4.04-39.75). According to the receiver operating characteristic analysis, CGI was significantly better than glycated haemoglobin and conventional CGM indicators for the prediction of adverse pregnancy outcomes (all p < .05). CONCLUSION: A lower CGI during pregnancy was associated with composite adverse outcomes and LGA. CGI, a novel glucose homeostasis predictor, seems to be superior to conventional glucose indicators for the prediction of adverse pregnancy outcomes in women with GDM.
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Automonitorización de la Glucosa Sanguínea , Glucemia , Diabetes Gestacional , Resultado del Embarazo , Humanos , Embarazo , Femenino , Diabetes Gestacional/sangre , Adulto , Estudios Retrospectivos , Glucemia/análisis , Glucemia/metabolismo , Resultado del Embarazo/epidemiología , Macrosomía Fetal/epidemiología , Macrosomía Fetal/etiología , Hemoglobina Glucada/análisis , Hemoglobina Glucada/metabolismo , Recién NacidoRESUMEN
Objective: To investigate the clinical characteristics and molecular epidemiology of carbapenem-resistant Klebsiella pneumoniae (CRKP) isolated from patients with bloodstream infections in a large tertiary-care general hospital in Southwest China. Methods: A total of 131 strains of non-repeating CRKP were collected from the blood cultures of patients who had bloodstream infections in 2015-2019. The strains were identified by VITEK-2, a fully automated microbial analyzer, and matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry. The minimum inhibitory concentration (MIC) was determined by microbroth dilution method. The common carbapenemase resistant genes and virulence factors were identified by PCR. Homology analysis was performed by multilocus sequencing typing. Whole genome sequencing was performed to analyze the genomic characteristics of CRKP without carbapenemase. Results: The 131 strains of CRKP showed resistance to common antibiotics, except for polymyxin B (1.6% resistance rate) and tigacycline (8.0% resistance rate). A total of 105 (80.2%) CRKP strains carried the Klebsiella pneumoniae carbapenemase (KPC) resistance gene, 15 (11.4%) strains carried the New Delhi Metallo-ß-lactamase (NDM) gene, and 4 (3.1%) isolates carried both KPC and NDM genes. Sequence typing (ST) 11 (74.0%) was the dominant sequence type. High detection rates for mrkD (96.2%), fimH (98.5%), entB (100%), and other virulence genes were reported. One hypervirulent CRKP strain was detected. The seven strains of CRKP that did not produce carbapenemase were shown to carry ESBL or AmpC genes and had anomalies in membrane porins OMPK35 and OMPK36, according to whole genome sequencing. Conclusion: In a large-scale tertiary-care general hospital, CRKP mainly carries the KPC gene, has a high drug resistance rate to a variety of antibiotics, and possesses multiple virulence genes. Attention should be paid to CRKP strains with high virulence.
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Proteínas Bacterianas , Carbapenémicos , Infecciones por Klebsiella , Klebsiella pneumoniae , Pruebas de Sensibilidad Microbiana , Epidemiología Molecular , Factores de Virulencia , beta-Lactamasas , Humanos , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/aislamiento & purificación , Klebsiella pneumoniae/patogenicidad , Proteínas Bacterianas/genética , beta-Lactamasas/genética , Infecciones por Klebsiella/microbiología , Infecciones por Klebsiella/epidemiología , China/epidemiología , Carbapenémicos/farmacología , Factores de Virulencia/genética , Antibacterianos/farmacología , Virulencia/genética , Masculino , Femenino , Enterobacteriaceae Resistentes a los Carbapenémicos/genética , Enterobacteriaceae Resistentes a los Carbapenémicos/aislamiento & purificación , Enterobacteriaceae Resistentes a los Carbapenémicos/efectos de los fármacos , Persona de Mediana Edad , Bacteriemia/microbiología , Bacteriemia/epidemiología , Secuenciación Completa del Genoma/métodosRESUMEN
Candida haemulonii, a relative of C. auris, frequently shows antifungal resistance and is transmissible. However, molecular tools for genotyping and investigating outbreaks are not yet established. We performed genome-based population analysis on 94 C. haemulonii strains, including 58 isolates from China and 36 other published strains. Phylogenetic analysis revealed that C. haemulonii can be divided into 4 clades. Clade 1 comprised strains from China and other global strains; clades 2-4 contained only isolates from China, were more recently evolved, and showed higher antifungal resistance. Four regional epidemic clusters (A, B, C, and D) were identified in China, each comprising ≥5 cases (largest intracluster pairwise single-nucleotide polymorphism differences <50 bp). Cluster A was identified in 2 hospitals located in the same city, suggesting potential intracity transmissions. Cluster D was resistant to 3 classes of antifungals. The emergence of more resistant phylogenetic clades and regional dissemination of antifungal-resistant C. haemulonii warrants further monitoring.
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Antifúngicos , Candida , Candidiasis , Farmacorresistencia Fúngica , Antifúngicos/uso terapéutico , Candida/efectos de los fármacos , Candida/genética , Candidiasis/tratamiento farmacológico , Candidiasis/genética , Candidiasis/microbiología , China , Pruebas de Sensibilidad Microbiana , Filogenia , Células Clonales , Farmacorresistencia Fúngica/genéticaRESUMEN
BACKGROUND: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has revolutionized microbial identification. However, there is a lack of data on its performance in identifying filamentous fungi. The objective of our study was to evaluate the accuracy of the Autof ms1000 mass spectrometry for identifying filamentous fungi in the clinical microbiology laboratory. RESULTS: Among 106 samples tested using the Autof ms1000 system, 101 (95.28%) were identified at the genus or species level, and 81 (76.41%) were accurately identified at the species level. Additionally, we developed a new rapid formic acid extraction method with simple pretreatment for filamentous fungi that saved time and provided accurate results. CONCLUSIONS: The Autof ms1000 mass spectrometer proved to be a valuable tool for identifying filamentous fungi. However, upgrading the database is recommended for correctly identifying rare strains.
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Hongos , Laboratorios , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Bases de Datos FactualesRESUMEN
Strokes are one of the leading causes of death and disability in the world. Previously we have found that conventional protein kinase Cγ (cPKCγ) plays neuroprotective role in ischemic strokes. Further, we found that cPKCγ knockdown increased the level of cleaved (cl)-Caspase-3. However, the precise mechanisms underlying cPKCγ-mediated neuronal death remain unclear. To this end, a model incorporating 1 h oxygen-glucose deprivation/24 h reoxygenation (1 h OGD/24 h R) was established in cortical neurons. We found that cPKCγ knockdown remarkably increased neuronal death after OGD. We also found that cPKCγ knockdown increased the level of cl-Caspase-3 through the upstream initiators Capsases-9 (not Caspase-8/12) in OGD-treated neurons. Overexpression of cPKCγ could decrease neuronal death and cl-Caspase-3 and -9 levels. Moreover, cPKCγ knockdown further reduced the phosphorylation levels of p38 MAPK, p90RSK, and Bad. In addition, the protein levels of Bcl-2 and Bcl-xl were decreased after cPKCγ knockdown, whereas that of Bax was increased. In conclusion, our results suggest that cPKCγ partly alleviates ischemic injury through activating the p38 MAPK-p90RSK-Bad pathway and inhibiting Caspase-9 initiated apoptosis. This may have potential as a therapeutic target for ischemic stroke.
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Daño por Reperfusión , Transducción de Señal , Apoptosis , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Glucosa/metabolismo , Isquemia/metabolismo , Neuronas/metabolismo , Oxígeno/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Reperfusión , Daño por Reperfusión/metabolismo , Proteínas Quinasas S6 Ribosómicas 90-kDa/metabolismo , Proteínas Quinasas S6 Ribosómicas 90-kDa/uso terapéutico , Animales , RatonesRESUMEN
BACKGROUND: Vitamin B6 is an essential water-soluble vitamin for humans. It is often used to prevent a variety of neuropathies, relieve vomiting, and relieve symptoms such as hand and foot neuritis. AIM: To evaluate whether vitamin B6 can alleviate the adverse reactions caused by the quadruple anti-Helicobacter pylori treatment regimen containing minocycline and metronidazole. METHODS: In this randomized controlled trial, 280 patients with H. pylori infection were randomly placed into one of two treatment groups-the conventional treatment group and the vitamin B6 supplement treatment group-for 2 weeks. The primary endpoint was the total incidence of adverse reactions up to 2 weeks after treatment initiation. The study was designed according to CONSORT Medicinal Interventions. And it was registered with Chinese Clinical Trial Registry under the number ChiCTR2100053833. RESULTS: In terms of efficacy, vitamin B6 does not affect the efficacy of conventional regimen. In the vitamin B6 supplement treatment group, the incidence of adverse reactions was 56.92%, which was significantly lower than the 74.62% observed in the conventional treatment group. In addition, the severity of adverse reactions was also significantly reduced. The proportion of moderate to severe central nervous system symptoms decreased from 58.7 to 14.63%. And, the proportion of moderate to severe gastrointestinal reactions decreased from 33.33 to 0%. We speculate that the mechanism of vitamin B6 of reducing adverse reaction may be related to the production of GABA in the brain. CONCLUSIONS: Vitamin B6 can alleviate adverse reactions of the quadruple anti-H. pylori regimen containing minocycline and metronidazole.
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Helicobacter pylori , Vitamina B 6 , Humanos , Vitamina B 6/uso terapéutico , Metronidazol/efectos adversos , Minociclina , Protocolos Clínicos , VitaminasRESUMEN
Although a phase II clinical trial confirmed that camrelizumab combined with apatinib is effective in patients with hepatocellular carcinoma (HCC), we generally lack data on the results of this regimen in real-world clinical practice. In this study, the efficacy and safety of camrelizumab combined with apatinib in the treatment of patients with HCC were re-evaluated. Data from 86 patients with HCC were collected and combinatorically treated with camrelizumab and apatinib at the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China. The objective remission rate and disease control rate were 25.6% and 72.1%, respectively. The median progression-free survival was 5 months (95% CI 3.7-6.3 months), and the median overall survival time was 19.0 months (95% CI 16.9-21.1 months). The 12- and 18-month survival rates were 70.9% and 54.2%, respectively. The most common grade 3-4 adverse events were hypertension (24.4%), thrombocytopenia (16.3%), and hyperbilirubinemia (9.3%). Multivariate regression analysis showed that operation history was an independent risk factor for overall survival.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
The Taiwanese people are composed of diverse indigenous populations and the Taiwanese Han. About 95% of the Taiwanese identify themselves as Taiwanese Han, but this may not be a homogeneous population because they migrated to the island from various regions of continental East Asia over a period of 400 years. Little is known about the underlying patterns of genetic ancestry, population admixture, and evolutionary adaptation in the Taiwanese Han people. Here, we analyzed the whole-genome single-nucleotide polymorphism genotyping data from 14,401 individuals of Taiwanese Han collected by the Taiwan Biobank and the whole-genome sequencing data for a subset of 772 people. We detected four major genetic ancestries with distinct geographic distributions (i.e., Northern, Southeastern, Japonic, and Island Southeast Asian ancestries) and signatures of population mixture contributing to the genomes of Taiwanese Han. We further scanned for signatures of positive natural selection that caused unusually long-range haplotypes and elevations of hitchhiked variants. As a result, we identified 16 candidate loci in which selection signals can be unambiguously localized at five single genes: CTNNA2, LRP1B, CSNK1G3, ASTN2, and NEO1. Statistical associations were examined in 16 metabolic-related traits to further elucidate the functional effects of each candidate gene. All five genes appear to have pleiotropic connections to various types of disease susceptibility and significant associations with at least one metabolic-related trait. Together, our results provide critical insights for understanding the evolutionary history and adaption of the Taiwanese Han population.
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Pueblo Asiatico , Genoma , Pueblo Asiatico/genética , Estudio de Asociación del Genoma Completo , Haplotipos , Humanos , Polimorfismo de Nucleótido SimpleRESUMEN
INTRODUCTION: Endoscopic biliary brushing is the most common method used for sampling in patients with malignant biliary strictures (MBSs); however, its sensitivity is relatively low. There is still no consensus on endoscopy-based biliary brushing, although brushing 10 times in 1 specimen is routinely performed. This study was designed to compare the sensitivity of brush cytology for 10, 20, or 30 brushing times of a pass in 1 specimen in patients with MBSs. METHODS: In this multicenter, prospective, randomized controlled study, patients who underwent endoscopic retrograde cholangiopancreatography for suspected MBSs were enrolled. Patients were randomly assigned to receive 10, 20, and 30 brushing times of a pass. The primary outcome was to compare the sensitivity of brush cytology among the 3 groups. Patients were prospectively followed up for 6 months after endoscopic brushing for malignancy diagnosis. RESULTS: A total of 443 patients were enrolled for intention-to-treat analysis (147, 148, and 148 patients in the 10-times, 20-times, and 30-time groups, respectively). The 3 groups were similar in baseline characteristics. The sensitivity of brush cytology was 38%, 47%, and 57% in the 10-times, 20-times, and 30-times groups, respectively, and the 30-times group showed significantly higher sensitivity than the 10-times group (P = 0.001). The multivariate analysis revealed that stricture length and the number of brushing passes were significant factors for the detection of biliary malignancy. No significant differences were observed in procedure-related complications among the 3 groups. DISCUSSION: Brushing 30 times could increase the diagnostic sensitivity without increasing complications and seems to be preferred for the endoscopic sampling and diagnosis of MBSs (chictr.org.cn, identifier: ChiCTR1800015978).
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Neoplasias de los Conductos Biliares , Neoplasias del Sistema Biliar , Colestasis , Neoplasias de los Conductos Biliares/complicaciones , Neoplasias de los Conductos Biliares/diagnóstico , Neoplasias de los Conductos Biliares/patología , Colangiopancreatografia Retrógrada Endoscópica , Colestasis/diagnóstico , Colestasis/etiología , Colestasis/patología , Constricción Patológica/diagnóstico , Constricción Patológica/etiología , Humanos , Estudios Prospectivos , Sensibilidad y EspecificidadRESUMEN
Colonization factor CFA/I defines the major adhesive fimbriae of enterotoxigenic Escherichia coli and mediates bacterial attachment to host intestinal epithelial cells. The CFA/I fimbria consists of a tip-localized minor adhesive subunit, CfaE, and thousands of copies of the major subunit CfaB polymerized into an ordered helical rod. Biosynthesis of CFA/I fimbriae requires the assistance of the periplasmic chaperone CfaA and outer membrane usher CfaC. Although the CfaE subunit is proposed to initiate the assembly of CFA/I fimbriae, how it performs this function remains elusive. Here, we report the establishment of an in vitro assay for CFA/I fimbria assembly and show that stabilized CfaA-CfaB and CfaA-CfaE binary complexes together with CfaC are sufficient to drive fimbria formation. The presence of both CfaA-CfaE and CfaC accelerates fimbria formation, while the absence of either component leads to linearized CfaB polymers in vitro. We further report the crystal structure of the stabilized CfaA-CfaE complex, revealing features unique for biogenesis of Class 5 fimbriae.
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Adhesinas Bacterianas/metabolismo , Escherichia coli Enterotoxigénica/fisiología , Proteínas de Escherichia coli/metabolismo , Proteínas Fimbrias/metabolismo , Fimbrias Bacterianas/fisiología , Chaperonas Moleculares/metabolismo , Secuencia de Aminoácidos , Citoplasma , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/genética , Proteínas Fimbrias/genética , Chaperonas Moleculares/genética , Conformación Proteica , Homología de Secuencia de AminoácidoRESUMEN
A Gram-negative, aerobic, non-flagellated and rod-shaped bacterium, strain ASW11-22T, was isolated from an intertidal sediment collected from a coastal area of Qingdao, PR China. The strain grew at 15-40 °C (optimum, 37 °C), at pH 6.0-9.0 (optimum, pH 7.0) and with 0.5-10â% (w/v) NaCl (optimum, 1.0â%). It hydrolysed gelatin and aesculin but did not reduce nitrate to nitrite. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain ASW11-22T belonged to the genus Celeribacter, showing the highest sequence similarity to the type strains of Celeribacter halophilus MCCC 1A06432T (98.20â%) and Celeribacter ethanolicus NH195T (97.84â%). The genomic DNA G+C content was 59.1 mol%. The major cellular fatty acid (>10â%) of the strain was summed feature 8 (C18â:â1 ω7c and/or C18â:â1 ω6c) and its main polar lipids were phosphatidylglycerol and one unidentified aminolipid. The sole respiratory quinone of strain ASW11-22T was ubiquinone-10. On the basis of the polyphasic evidence presented in this paper, strain ASW11-22T represents a novel Celeribacter species, for which the name Celeribacter litoreus sp. nov. is proposed. The type strain is ASW11-22T (=KCTC 82495T=MCCC 1K05584T).
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Alphaproteobacteria/clasificación , Sedimentos Geológicos , Filogenia , Agua de Mar , Alphaproteobacteria/aislamiento & purificación , Técnicas de Tipificación Bacteriana , Composición de Base , China , ADN Bacteriano/genética , Ácidos Grasos/química , Sedimentos Geológicos/microbiología , Fosfolípidos/química , ARN Ribosómico 16S/genética , Agua de Mar/microbiología , Análisis de Secuencia de ADN , Ubiquinona/análogos & derivados , Ubiquinona/químicaRESUMEN
Cryptococcus is an opportunistic pathogenic fungus and is the major cause of fungal meningitis. The cryptococcal antigen (CrAg) lateral flow assay (LFA) is an immunochromatographic test system that has simplified diagnosis as a point-of-care test. In this study, we evaluated the diagnostic performance of Cryptococcal capsular polysaccharide detection FungiXpert (Genobio Pharmaceutical, Tianjin, China) using serum and cerebrospinal fluid (CSF) samples for the diagnosis of cryptococcosis and investigated the cross-reaction of the assays to pathogenic fungi and bacterium by comparing it to the U.S. Food and Drug Administration (US FDA)-approved IMMY CrAg LFA. Eighty CSF and 119 serum/plasma samples from 158 patients were retrospectively collected to test for qualitative or semi-quantitative detection of CrAg. Cross-reaction of the assays was tested using 28 fungi and 1 bacterium. Compared to IMMY CrAg LFA, the FungiXpert LFA demonstrated 99.1% sensitivity and 98.9% specificity in the qualitative test. In the 96 semi-quantitative CrAg assay results, 39 (40.6%) test titers of FungiXpert LFA were 1-2 dilutions higher than those of IMMY CrAg LFA. The Intraclass Correlation Coefficient of the Semi-quantitative results of CrAg titer tests via the two assays was 0.976. Similar to IMMY CrAg LFA, FungiXpert LFA showed cross-reactivity with Trichosporon asahii. Compared with the IMMY CrAg LFA, the FungiXpert LFA showed an equal, yet, excellent performance. However, it is important to note that these two assays have potential cross-reactivity to T. asahii when diagnosing patients. FungiXpert LFA is a rapid screening method for the effective and practical diagnosis and treatment of cryptococcosis. LAY SUMMARY: The FungiXpert LFA was developed to diagnose fungal meningitis caused by Cryptococcus yeasts, by using serum or cerebrospinal fluid. It was compared to an existing lateral flow assay (LFA). The FungiXpert LFA performed well in qualitative and semi-quantitative tests.
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Criptococosis , Cryptococcus , Infecciones por VIH , Meningitis Criptocócica , Meningitis Fúngica , Animales , Antígenos Fúngicos , Criptococosis/diagnóstico , Criptococosis/veterinaria , Infecciones por VIH/veterinaria , Meningitis Criptocócica/diagnóstico , Meningitis Criptocócica/veterinaria , Meningitis Fúngica/veterinaria , Polisacáridos , Estudios RetrospectivosRESUMEN
BACKGROUND: T1 colorectal cancers have a low lymph node metastasis rate and good prognosis. Thus, endoscopic resection is an attractive choice. This study aimed to describe the value of poorly differentiated cluster grade in identifying endoscopically curable T1 colorectal cancers. METHODS: We included 183 T1 colorectal cancer patients who underwent curative resection. Univariate and multivariate logistic regressions were used to identify lymph node metastasis predictors. The Akaike information criterion was used to determine whether poorly differentiated cluster grade was the best predictor. Backward regression was used to screen the variables. Survival analyses were conducted to determine the prognostic predictive power of poorly differentiated cluster grade. Correlations among predictors and concordance between our pathologists were also investigated. RESULTS: Poorly differentiated cluster grade was an independent predictor for lymph node metastasis (adjusted odds ratio [OR]G 3 = 0.001; 95% confidence interval [95% CI]G 3 = < 0.001, 0.139) in T1 colorectal cancer patients; moreover, it had the best predictive value (AIC = 61.626) among all indicators. It was also screened for inclusion in the predictive model. Accordingly, a high poorly differentiated cluster grade independently indicated shorter overall survival (hazard ratio [HR]G 2 = 4.315; 95% CIG 2 = 1.506, 12.568; HRG 3 = 5.049; 95% CIG 3 = 1.326, 19.222) and disease-free survival (HRG 3 = 6.621; 95% CIG 3 = 1.472, 29.786). CONCLUSIONS: Poorly differentiated cluster grade is a vital reference to manage T1 colorectal cancer. It could serve as an indicator to screen endoscopically curable T1 colorectal cancers.
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Neoplasias Colorrectales , Neoplasias Colorrectales/patología , Humanos , Metástasis Linfática , Pronóstico , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Objective: To investigate the distribution of pathogenic bacteria in blood samples and changes in their drug resistance in our hospital from 2016 to 2020, and to provide evidence for the diagnosis and treatment of clinical bloodstream infections. Methods: Bruker Corporation's matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) was used for bacterial identification, VITEK 2 Compact was used for antimicrobial susceptibility test, some of which was done with the Kirby-Bauer method, and the data was statistically analyzed with WHONET 5.6 software. Results: A total of 8931 bacterial strains, including 4502 (50.4%) Gram-positive bacteria and 4429 (49.6%) Gram-negative bacteria, were isolated from the blood samples between 2016 and 2020. Among the isolated bacteria of the order Enterobacterales, Escherichia coli (1773, 19.9%) ranked first, followed by Klebsiella pneumoniae (1067, 11.9%). The non-fermenting bacteria identified were predominantly Acinetobacter baumannii (293, 3.3%) and Pseudomonas aeruginosa (238, 2.7%). The top three Staphylococcus species were Staphylococcus epidermidis (970 strains, 10.9%), Staphylococcus hominis (713, 8.0%) and Staphylococcus aureus (541, 6.1%). Escherichia coli showed high in vitro susceptibility to cefoperazone/sulbactam, amikacin, polymyxin B, tigecycline, and carbapenems, and the sensitivity rate was consistently over 90%. The resistance rate to imipenem showed a trend of slow growth, and the resistance rate of meropenem was 2.2% to 3.4%. Klebsiella pneumoniae showed higher in vitro resistance rate to common antibiotics than that of Escherichia coli, with only the sensitivity rates to tigecycline and polymyxin B being higher than 90%, and the resistance rate to imipenem and meropenem increasing year by year. The resistance rate of Pseudomonas aeruginosa to imipenem decreased since 2017 (from 25.6% to18.6%), and the resistance rate of Acinetobacter baumanniito imipenem and meropenem were 73.7%-91.3% and 73.0%-91.3%. Staphylococcus resistant to vancomycin or linezolid was not found. Enterococci showed rather low resistance to vancomycin and linezolid. Conclusion: The distribution of common species of pathogenic bacteria in clinical blood samples in our hospital did not show significant changes, but the problem of multi-drug resistant bacteria is becoming increasingly more serious, especially so for carbapenem-resistant Klebsiella pneumoniae.
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Farmacorresistencia Bacteriana , Vancomicina , Antibacterianos/farmacología , Bacterias , Escherichia coli , Bacterias Gramnegativas , Hospitales de Enseñanza , Imipenem , Klebsiella pneumoniae , Meropenem , Pruebas de Sensibilidad Microbiana , Polimixina B , Pseudomonas aeruginosa , TigeciclinaRESUMEN
Type II toxin-antitoxin (TA) systems modulate many essential cellular processes in prokaryotic organisms. Recent studies indicate certain type II antitoxins also transcriptionally regulate other genes, besides neutralizing toxin activity. Herein, we investigated the diverse transcriptional repression properties of type II TA antitoxin PaHigA from Pseudomonas aeruginosa. Biochemical and functional analyses showed that PaHigA recognized variable pseudopalindromic DNA sequences and repressed expression of multiple genes. Furthermore, we presented high resolution structures of apo-PaHigA, PaHigA-PhigBA and PaHigA-Ppa2440 complex, describing how the rearrangements of the HTH domain accounted for the different DNA-binding patterns among HigA homologues. Moreover, we demonstrated that the N-terminal loop motion of PaHigA was associated with its apo and DNA-bound states, reflecting a switch mechanism regulating HigA antitoxin function. Collectively, this work extends our understanding of how the PaHigB/HigA system regulates multiple metabolic pathways to balance the growth and stress response in P. aeruginosa and could guide further development of anti-TA oriented strategies for pathogen treatment.
Asunto(s)
Antitoxinas , Sistemas Toxina-Antitoxina , Antitoxinas/genética , Proteínas Bacterianas/genética , Motivos de Nucleótidos , Pseudomonas aeruginosa/genéticaRESUMEN
To investigated the molecular epidemiology and in vitro antifungal susceptibility of Cryptococcus isolates from West China Hospital from HIV and non-HIV patients between 2009 and 2015. A total of 132 C. neoformans and C. gattii were subjected to antifungal susceptibility testing by E-test method. Among the 132 isolates, 42 C. neoformans and C. gattii were analyzed by mating type and URA5-RFLP. A total of 113 C. neoformans and C. gattii were subjected to multi-locus sequence typing (MLST). MLST results revealed that ST5 was the major molecular type. The wild-type (WT) phenotype was seen in 91.5-100% of C. neoformans isolates for amphotericin B, 5-flucytosine, fluconazole, and voriconazole. However, 72.3% (94/130) of C. neoformans isolates were non-wild-type (non-WT) to itraconazole by E-test method. In the sixth study year, the geometric mean, MIC50 and MIC90 of fluconazole were the highest (P < 0.001). Among 132 patients. 52 were coinfected with HIV and 80 were HIV-negative. Isolates from HIV and non-HIV patients showed no differences in susceptibility to amphotericin B (P = 0.544), 5-flucytosine (P = 0.063), fluconazole (P = 0.570), voriconazole (P = 0.542), and itraconazole (P = 0.787). Our study showed that Cryptococcus in southwest China showed a low degree of genetic diversity. The increased MIC values of fluconazole are noted. Cryptococcus isolates from HIV and non-HIV patients have shown no differences in susceptibility to five antifungal agents.
Asunto(s)
Antifúngicos/farmacología , Criptococosis , Cryptococcus gattii , Cryptococcus neoformans , Farmacorresistencia Fúngica/genética , Infecciones por VIH/epidemiología , Adolescente , Adulto , Anciano , China/epidemiología , Criptococosis/epidemiología , Criptococosis/microbiología , Cryptococcus gattii/efectos de los fármacos , Cryptococcus gattii/genética , Cryptococcus neoformans/efectos de los fármacos , Cryptococcus neoformans/genética , Femenino , Variación Genética , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
BACKGROUND: Cancer patients often exhibit chemotherapy-associated changes in serum lipid profiles, however, their prognostic value before and after adjuvant chemotherapy on survival among non-small-cell lung cancer (NSCLC) patients is unknown. METHODS: NSCLC patients undergoing radical resection and subsequent adjuvant chemotherapy from 2013 to 2017 at Sun Yat-sen University Cancer Center were retrospectively reviewed. Fasted serum lipid levels were measured before and after chemotherapy. The optimal lipid cut-off values at baseline and fluctuation were determined using X-tile™. The fluctuations in serum lipid levels and disease-free survival (DFS) were assessed. RESULTS: Serum cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglyceride, apolipoprotein (Apo) A-I, and ApoB all significantly increased after adjuvant chemotherapy. X-tile determined 1.52 mmol/L of HDL-C and 0.74 g/L of ApoB as the optimal cut-off values before chemotherapy. Patients with HDL-C ≥ 1.52 mmol/L (median DFS: not reached vs. 26.30 months, P = 0.0005) and a decreased HDL-C level after adjuvant chemotherapy (median DFS: 80.43 vs. 26.12 months, P = 0.0204) had a longer DFS. An HDL-C level that increased by ≥ 0.32 mmol/L after chemotherapy indicated a worse DFS. A high baseline ApoB level were associated with a superior DFS. In the univariate analysis and the multivariate Cox analyses, a high baseline HDL-C level and a HDL-C reduction after adjuvant chemotherapy were independent indicators for superior DFS. High baseline HDL-C was related to N0-1 stage (χ2 = 6.413, P = 0.011), and HDL-C fluctuation was significantly correlated with specific chemotherapy regimens (χ2 = 5.002, P = 0.025). CONCLUSIONS: Adjuvant chemotherapy increased various lipid levels in resected NSCLC patients. A higher HDL-C level before chemotherapy and a reduced HDL-C level after adjuvant chemotherapy were independent predictors of longer DFS in patients with curable NSCLC.