Diagnostic efficiency of the FilmArray blood culture identification (BCID) panel: a systematic review and meta-analysis.

Introduction. The FilmArray blood culture identification panel (BCID) panel is a multiplex PCR assay with high sensitivity and specificity to identify the most common pathogens in bloodstream infections (BSIs).Hypothesis. We hypothesize that the BCID panel has good diagnostic performance for BSIs and can be popularized in clinical application.Aim: To provide summarized evidence for the diagnostic accuracy of the BCID panel for the identification of positive blood cultures.Methodology. We searched the MEDLINE, EMBASE and Cochrane databases through March 2021 and assessed the efficacy of the diagnostic test of the BCID panel. We performed a meta-analysis and calculated the summary sensitivity and specificity of the BCID panel. Systematic review protocols were registered in the International Prospective Register of Systematic Reviews (PROSPERO) (registration number CRD42021239176).Results. A total of 16 full-text articles were eligible for analysis. The overall sensitivities of the BCID panel on Gram-positive bacteria, Gram-negative bacteria and fungi were 97 % (95 % CI, 0.96-0.98), 100 % (95 % CI, 0.98-01.00) and 99 % (95 % CI, 0.87-1.00), respectively. The pooled diagnostic specificities were 99 % (95 % CI, 0.97-1.00), 100 % (95 % CI, 1.00-1.00) and 100 % (95 % CI, 1.00-1.00) for Gram-positive bacteria, Gram-negative bacteria and fungi, respectively.Conclusions. The BCID panel has high rule-in value for the early detection of BSI patients. The BCID panel can still provide valuable information for ruling out bacteremia or fungemia in populations with low pretest probability.

A More Comprehensive Clinical and Laboratory Characterization of 61 Acute HIV Infection Patients in Southwest China.

Acute HIV infection (AHI), i.e., the early stage of HIV infection, plays an important role in immune system failure and HIV transmission, but most AHI patients are missed due to their non-specific symptoms. To facilitate the identification of patients with high AHI risk and reduction of missed diagnosis, we characterized 61 AHI patients in a Southwest China hospital with 4300 beds; specifically, we characterized their general clinical characteristics, evolution in results of a novel HIV screening assay called Elecsys® HIV Duo, and by programming, we analyzed the ability of all routine laboratory tests (e.g., routine blood analysis) to identify AHI patients. Among 61 AHI patients, 85.2% were male and the median age was 42 (interquartile range, 25-62) years. A total of 61.9% of patients visit the emergency department first during AHI. Clinical presentation of AHI patients included fever, fatigue, chills, rash, and various respiratory, digestive, and nervous system symptoms. Two of three results from Elecsys® HIV Duo show clear evolution trends: HIV P24 antigen decreased while HIV antibody increased in consecutive samples of nearly all patients. High fluorescence lymphocytes have a very high positive likelihood ratio (LR+) of 10.33 and a relatively high "rate of out-of-range tests" of 56.8% (21 in 37 patients who received this test had a result outside the reference range). In addition, we identified more than ten tests with LR+ greater than two. In summary, the emergency department is important for AHI screening. The evolution of HIV P24 Ag and HIV Ab and those laboratory tests with a high "rate of out-of-range tests" or high LR+ may aid the AHI identification and missed diagnosis reduction.

Effect of IL-10 in the pathogenesis of HIV/AIDS patients with cryptococcal meningitis.

This study aimed to explore the role of IL-10 in the pathogenesis of HIV/AIDS patients with cryptococcal meningitis (CM).Patients were assigned into 4 groups (n = 40/group): group A (HIV/AIDS with CM), group B (HIV/AIDS with tuberculosis), group C (HIV/AIDS), and group D (CM). The levels of IL-10 and associated indicators were measured and the correlations were analyzed by Pearson correlation and partial correlation method. In plasma and cerebrospinal fluid (CSF), no significant difference was observed on IL-10 level between group A and other groups (P > 0.050). R values for IL-10 and relevant indicators in blood were as follows (P < 0.050): group A, IFN-γ (-0.377), IL-12 (0.743), IL-4 (0.881), and IL-6 (0.843); group B, IL-12 (0.740), IL-4 (0.573), and IL-6 (0.900); group C, IL-12 (0.402) and IL-4 (0.896); group D, IL-12 (0.575), IL-4 (0.852), and CD8 (0.325). R values for IL-10 and related indicators in CSF were as follows (P < 0.050): group A, TNF-α (0.664), IL-4 (0.852), white blood cells (WBCs, 0.321) and total protein (TP, 0.330); group B, TNF-α (0.566), IL-4 (0.702), and lactate dehydrogenase (LDH, 0.382); group D, IFN-γ (0.807) and IL-4 (0.441). IL-10 level was positively correlated with IL-4, IL-6, IL-12, TNF-α, WBC, and TP in blood or CSF, and negatively correlated with IFN-γ in blood, suggesting that IL-10 affected both pro-inflammatory and anti-inflammatory activities in the pathogenesis of HIV/AIDS with CM.

Causal relationships between metabolic-associated fatty liver disease and iron status: Two-sample Mendelian randomization.

BACKGROUND & AIMS: Dysregulated iron homeostasis plays an important role in the hepatic manifestation of metabolic-associated fatty liver disease (MAFLD). We investigated the causal effects of five iron metabolism markers, regular iron supplementation and MAFLD risk. METHODS: Genetic summary statistics were obtained from open genome-wide association study databases. Two-sample bidirectional Mendelian randomization analysis was performed to estimate the causal effect between iron status and MAFLD, including Mendelian randomization inverse-variance weighted, weighted median methods and Mendelian randomization-Egger regression. The Mendelian randomization-PRESSO outlier test, Cochran's Q test and Mendelian randomization-Egger regression were used to assess outliers, heterogeneity and pleiotropy respectively. RESULTS: Mendelian randomization inverse-variance weighted results showed that the genetically predicted per standard deviation increase in liver iron (Data set 2: odds ratio 1.193, 95% confidence interval [CI] 1.074-1.326, p = .001) was associated with an increased MAFLD risk, consistent with the weighted median estimates and Mendelian randomization-Egger regression, although Data set 1 was not significant. Mendelian randomization inverse-variance weighted analysis showed that genetically predicted MAFLD was significantly associated with increased serum ferritin levels in both datasets (Dataset 1: ß = .038, 95% CI = .014 to .062, p = .002; Dataset 2: ß = .081, 95% CI = .025 to .136, p = .004), and a similar result was observed with the weighted median methods for Dataset 2 instead of Mendelian randomization-Egger regression. CONCLUSIONS: This study uncovered genetically predicted causal associations between iron metabolism status and MAFLD. These findings underscore the need for improved guidelines for managing MAFLD risk by emphasizing hepatic iron levels as a risk factor and ferritin levels as a prognostic factor.

Circulating IL-1ß, IL-17, and IP-10 as Potential Predictors of Hepatitis B Virus Infection Prognosis.

Circulating cytokines and chemokines play critical roles in hepatitis B virus (HBV) infection. Here, we explored the effects of proinflammatory and anti-inflammatory effector molecules on HBV progression, e antigen seroconversion, and liver function. Our results showed that circulating interleukin (IL)-17 may be helpful in HBV spontaneous clearance [odds ratio (OR) = 1.468, 95%confidence interval (CI) = 1.080-1.995, P = 0.014] and protective against HBV-related hepatoma development (OR = 0.933, 95%CI = 0.910-0.957, P < 0.001). IL-1ß negatively affected HBV clearance (OR = 0.052, 95%CI = 0.005-0.534, P = 0.013). In patients with chronic hepatitis B, interferon-γ-inducible protein-10 (IP-10) levels significantly increased in the group of abnormal liver function (P = 0.006). Furthermore, positive correlations of IP-10 with alanine aminotransferase and aspartate aminotransferase levels were observed (r s = 0.546 and 0.644, respectively; P < 0.001). In conclusion, inflammatory cytokines and chemokines may be a "double-edged sword" for HBV clearance and progression. Further exploration of the roles of IL-17, IL-1ß, and IP-10 in chronic HBV infection is needed.

Recent advances in metal-organic frameworks and their composites for the phototherapy of skin wounds.

Wound healing is a complex process that greatly affects the normal physiological activities of genes, proteins, signaling pathways, tissues, and organs. Bacterial infection could easily lead to serious tissue damage during wound healing, thus countering wound infections becomes a major challenge for clinicians and nursing professionals. At present, the exploration of highly effective, low toxicity and environment friendly methods for wound healing is attracting considerable interest all over the world. Recently, metal-organic frameworks (MOFs) have presented great potential for treating wound infections due to their unique characteristics of diversified functionality, large specific surface area, and high biocompatibility. These properties endow MOFs/MOF-based composites with an outstanding anti-wound infection effect, which is mainly attributed to the continuously released active components and the exerted catalytic activity with the assistance of phototherapy. In this review, the current progress of MOFs/MOF-based composites for the phototherapy of skin wounds is presented. Firstly, we illustrate the pathophysiological mechanisms, principles of phototherapy and the conventional methods for wound healing. Then, the structures and characteristics of MOFs are systematically summarized. Moreover, the review highlights the recent advances in the application of phototherapy for wound healing (including photodynamic therapy, photothermal therapy, and synergistic therapy) based on various MOFs/MOF-based composites. Finally, the challenges and perspectives are provided for the further development of MOF-based materials for medical application.

Clinical Application Evaluation of Elecsys® HIV Duo Assay in Southwest China.

Background: HIV/AIDS continues to be a serious health concern of morbidity and mortality globally, and novel HIV testing is still an important component of diagnosing HIV earlier and reducing the spread of HIV. The Elecsys® HIV Duo assay is a 4th generation assay that can detect both HIV-1 p24 antigen (Ag) and HIV-1/2 antibody (Ab) in parallel and show the subresults for the Ab and Ab units. Objectives: To evaluate the clinical performance of the Elecsys® HIV Duo assay on the new cobas E 801 analyzer using a large number of clinical samples from a population in southwest China. Methods: We collected testing results and information from all patients in a large general hospital. All eligible clinical specimens were first analyzed using the Elecsys® HIV Duo assay. The test results are given either as reactive or nonreactive as well as in the form of a cutoff index (COI). All initially reactive specimens were retested in duplicate with a 3rd-generation kit. Supplementary tests were divided into Ab confirmation tests and HIV-1 nucleic acid tests. GraphPad Prism and Python were used for plotting, and SPSS 21.0 software was used for statistical analysis. Results: A total of 186391 specimens were received, and 436 patients were confirmed to be positive for HIV. Among the 86 cases with contact history available, there were more males than females, and heterosexual transmission was the most common route of HIV infection. The Elecsys® HIV Duo assay displayed 99.94%, 99.93% and 99.98% specificity for inpatient, outpatient and physical examination patients, respectively. The median COI ratios of the false-positive group were significantly lower than those of the true-positive group. Conclusions: The Elecsys® HIV Duo test (Cobase801 analyzer) differentiates the detection of HIV-1 p24 Ag and HIV-1/2 Ab with high specificity and facilitates the diagnosis of patients with early HIV infection. Therefore, the Elecsys®HIV Duo test is used for differentiation of antigen and antibody reactivity, making it suitable for routine clinical diagnosis.

Recent advances in metal-organic framework-based materials for anti-staphylococcus aureus infection.

The rapid spread of staphylococcus aureus (S. aureus) causes an increased morbidity and mortality, as well as great economic losses in the world. Anti-S. aureus infection becomes a major challenge for clinicians and nursing professionals to address drug resistance. Hence, it is urgent to explore high efficiency, low toxicity, and environmental-friendly methods against S. aureus. Metal-organic frameworks (MOFs) represent great potential in treating S. aureus infection due to the unique features of MOFs including tunable chemical constitute, open crystalline structure, and high specific surface area. Especially, these properties endow MOF-based materials outstanding antibacterial effect, which can be mainly attributed to the continuously released active components and the exerted catalytic activity to fight bacterial infection. Herein, the structural characteristics of MOFs and evaluation method of antimicrobial activity are briefly summarized. Then we systematically give an overview on their recent progress on antibacterial mechanisms, metal ion sustained-release system, controlled delivery system, catalytic system, and energy conversion system based on MOF materials. Finally, suggestions and direction for future research to develop and mechanism understand MOF-based materials are discussed in antibacterial application.

Fluorescence and visual immunoassay of HIV-1 p24 antigen in clinical samples via multiple selective recognitions of CdTe QDs.

Human immunodeficiency virus (HIV) infection inflicts significant economic and social burdens on many countries worldwide. Given the substantial morbidity and mortality from HIV infection, there is an urgent need for accurate and early detection of the virus. In this study, immunofluorescence and visual techniques are described that detect the HIV-1 p24 antigen, which relied on selective recognition of Ag+/Ag nanoparticles (Ag NPs) and Cu2+/Cu+ using cadmium telluride quantum dots (CdTe QDs). After the sandwich immunoreactions were accomplished, the alkaline phosphatase (ALP) hydrolyzed L-ascorbic acid 2-phosphate (AAP) to form ascorbic acid (AA) that further reduces Ag+ and Cu2+ to Ag NPs and Cu+, respectively. This method was highly sensitive and selective and could detect as low as 1 pg/mL of p24 antigen by naked eyes and had a good linearity in the concentration range 1-100 pg/mL. When using Ag+ and Cu2+ as media, the limit of detection (LOD) of the new method was 0.3 pg/mL and 0.2 pg/mL, respectively. Compared with clinical electrochemiluminescence immunoassay (ECLIA) results and clinical data, this method demonstrated good consistency for the quantification of HIV-1 p24 antigen in 34 clinical serum samples. In addition, this method could accurately distinguish HIV from other viruses and infections such as hepatitis B virus, systemic lupus erythematosus, hepatitis C virus, Epstein-Barr virus, cytomegalovirus, lipemia, and hemolysis. Therefore, our dual-mode analysis method may provide additional solutions to identify clinical HIV infection. An immunofluorescence and visualization dual-mode strategy for the detection of p24 antigen was constructed based on immune recognition reaction and a phenomenon that cadmium telluride quantum dots (CdTe QDs) can selectively recognize Ag+/Ag nanoparticles (Ag NPs) and Cu2+/Cu+.

Pyrotinib in vitro metabolite profiling via rat, dog and human hepatocytes using liquid chromatography-quadrupole/orbitrap mass spectrometry.

RATIONALE: Pyrotinib is an irreversible EGFR/HER2 inhibitor that has shown antitumor activity and tolerance in the treatment of breast cancer. Studies focused on its metabolic pathways and major metabolites are insufficient. In the evaluation of drug safety and therapeutic use, metabolite characterization is critical. The metabolism of pyrotinib in vitro was studied utilizing rat, dog and human hepatocytes in this study. METHODS: Pyrotinib (10 µM) was incubated with hepatocytes in Williams' E medium. The metabolites were examined and profiled using ultrahigh-performance liquid chromatography coupled with quadrupole/orbitrap high-resolution mass spectrometry. The metabolite structures were deduced by comparing their precise molecular weights, fragment ions and retention times with those of the parent drug. RESULTS: A total of 16 metabolites, including 6 novel ones, were discovered and structurally described under the present conditions. Oxidation, demethylation, dehydrogenation, O-dealkylation and glutathione (GSH) conjugation were all involved in the metabolism of pyrotinib in hepatocytes. The most predominant metabolic route was identified as GSH conjugation (M5). CONCLUSIONS: This study generated valuable metabolite profiles of pyrotinib in several species, which will aid in the understanding of the drug's disposition in various species and in evaluating the contribution of metabolites to overall effectiveness and toxicity of pyrotinib.

Novel Long Non-coding RNA and LASSO Prediction Model to Better Identify Pulmonary Tuberculosis: A Case-Control Study in China.

INTRODUCTION: The insufficient understanding and misdiagnosis of clinically diagnosed pulmonary tuberculosis (PTB) without an aetiological evidence is a major problem in the diagnosis of tuberculosis (TB). This study aims to confirm the value of Long non-coding RNA (lncRNA) n344917 in the diagnosis of PTB and construct a rapid, accurate, and universal prediction model. METHODS: A total of 536 patients were prospectively and consecutively recruited, including clinically diagnosed PTB, PTB with an aetiological evidence and non-TB disease controls, who were admitted to West China hospital from Dec 2014 to Dec 2017. The expression levels of lncRNA n344917 of all patients were analyzed using reverse transcriptase quantitative real-time PCR. Then, the laboratory findings, electronic health record (EHR) information and expression levels of n344917 were used to construct a prediction model through the Least Absolute Shrinkage and Selection Operator algorithm and multivariate logistic regression. RESULTS: The factors of n344917, age, CT calcification, cough, TBIGRA, low-grade fever and weight loss were included in the prediction model. It had good discrimination (area under the curve = 0.88, cutoff = 0.657, sensitivity = 88.98%, specificity = 86.43%, positive predictive value = 85.61%, and negative predictive value = 89.63%), consistency and clinical availability. It also showed a good replicability in the validation cohort. Finally, it was encapsulated as an open-source and free web-based application for clinical use and is available online at https://ziruinptb.shinyapps.io/shiny/. CONCLUSION: Combining the novel potential molecular biomarker n344917, laboratory and EHR variables, this web-based prediction model could serve as a user-friendly, accurate platform to improve the clinical diagnosis of PTB.

Relationships between IL-1ß, TNF-α genetic polymorphisms and HBV infection: A meta-analytical study.

BACKGROUND: IL-1ß and TNF-α have been demonstrated as pro-inflammatory cytokines to participate in the innate immune response and suppression of HBV infection. However, the exact relationship between IL-1ß, TNF-α gene polymorphisms and HBV infection remains unknown. Our study aims to assess the associations between IL-1ß, TNF-α gene polymorphisms and HBV infection. METHODS: A systematic literature search of PubMed and Embase databases was conducted through February 2020, and studies that were included in the present meta-analysis should fulfil the following conditions: (1) case-control studies focusing on the associations between IL-1ß, TNF-α polymorphisms and HBV infection; (2) patients in the case group should be tested positive for the HBsAg and/or HBV-DNA without liver cirrhosis or hepatocellular carcinoma; (3) the control group including healthy population or HBV spontaneous clearance population; (4) odds ratios (ORs) and their 95% confidence intervals (CIs) could be calculated based on the allele and genotype frequencies provided in articles. The quality of included studies was assessed according to the Newcastle-Ottawa scale (NOS) assessment system. Pooled ORs and 95% CIs were used to analyze the strength of associations. Subgroup analysis was performed according to ethnicity and control type. RESULTS: In the present meta-analysis, 49 articles including 10,218 cases and 9,557 controls were enrolled and seven polymorphisms (IL-1ß rs16944, rs1143634, TNF-α rs1799724, rs1799964, rs1800629, rs1800630, rs361525) were studied. In overall meta-analysis, significant associations were found in IL-1ß rs1143634, TNF-α rs1799724 and TNF-α rs1799964. For subgroup analysis under ethnicity, TNF-α rs1799724 and rs1800630 were markedly related to HBV infection in both Asian and Caucasian populations. In terms of control type subgroup, TNF-α rs1799724, rs1799964, rs1800630 were significantly associated with HBV persistence in HBV spontaneous clearance group. CONCLUSION: In the present study, we identified that three polymorphisms (IL-1ß rs1143634, TNF-α rs1799724, rs1799964) might serve as potential genetic biomarkers in HBV infection.

Diagnostic role of CXCL13 and CSF serology in patients with neurosyphilis.

BACKGROUND: Considering the unknown prevalence of neurosyphilis in West China, and the confusing diagnosis of neurosyphilis, the role of CSF_CXCL13 and syphilis serology was studied to provide a more accurate reference for the clinical detection and diagnosis of neurosyphilis. METHODS: A retrospective data set I was used to investigate the prevalence of neurosyphilis, as well as the laboratory characteristics of 244 patients. Besides, to explore the diagnostic value of CSF_CXCL13 and syphilis serology for neurosyphilis, another 116 CSF_serum paired samples (data set II) were collected from 44 neurosyphilis and 72 non-neurosyphilis/syphilis patients. RESULTS: About 6.25% (156 out of 2494) syphilis was neurosyphilis. When Treponema pallidum infection occurs, syphilis serology (sero_TRUST ≥1:16 and sero_TPPA titre ≥1:10240) can be good predictors of neurosyphilis, as well as syphilis CSF serology (CSF_TPPA ≥1:320, CSF_TRUST and venereal disease research laboratory). The sensitivity of serology in neurosyphilis can be complemented by CSF_CXCL13, which could be the therapy monitor of neurosyphilis. CONCLUSION: Due to the lack of ideal biomarkers for neurosyphilis, the importance of syphilis serology cannot be ignored, and their combination with CSF_CXCL13 or other biomarkers should be further investigated.

An enlightening role for cytokine storm in coronavirus infection.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in Wuhan, China has dispersed rapidly worldwide. Although most patients present with mild fever, cough with varying pulmonary shadows, a significant portion still develops severe respiratory dysfunction. And these severe cases are often associated with manifestations outside the respiratory tract. Currently, it is not difficult to find inflammatory cytokines upregulated in the blood of infected patients. However, some complications in addition to respiratory system with the coronavirus disease 2019 (COVID-19) are impossible to explain or cannot be attributed to virus itself. Thus excessive cytokines and their potentially fatal adverse effects are probably the answer to the multiple organ dysfunctions and growing mortality. This review provides a comprehensive overview of the mechanisms underlying cytokine storm, summarizes its pathophysiology and improves understanding of cytokine storm associated with coronavirus infections by comparing SARS-CoV-2 with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV).

Risk factor for intestinal carriage of carbapenem-resistant Acinetobacter baumannii and the impact on subsequent infection among patients in an intensive care unit: an observational study.

OBJECTIVES: To assess the incidence and the impact of carbapenem-resistant Acinetobacter baumannii (CRAB) intestinal carriage on subsequent CRAB infection and to study risk factors of acquiring CRAB intestinal carriage among patients in intensive care unit (ICU). DESIGN: Observational study including a case-control study and a retrospective cohort study. SETTING: A 50-bed general ICU of a university hospital, China. METHODS: From May 2017 to April 2018, an observational study was conducted in a 50-bed general ICU of a university hospital in China. Rectal swabs were collected from ICU patients on admission and thereafter weekly. A case-control study was performed to analyse risk factors of the acquisition of CRAB intestinal carriage in ICU using multiple logistic regression. A retrospective cohort study was performed to address whether intestinal CRAB carriage could lead to an increased likelihood of subsequent CRAB infection using subdistribution hazard model regarding death in the ICU as a competing risk event. RESULTS: CRAB intestinal carriage was detected in 6.87% (66/961; 95% CI 5.27% to 8.47%) of patients on ICU admission, whereas 11.97% (115/961; 95% CI 9.91% to 14.02%) of patients acquired CRAB intestinal carriage during the ICU stay. Pancreatitis (OR 2.16, 95% CI 1.28 to 3.67), haematological disease (OR 2.26, 95% CI 1.42 to 3.58), gastric tube feeding (OR 3.35, 95% CI 2.03 to 5.51) and use of carbapenems (OR 1.84, 95% CI 1.11 to 3.07) were independent risk factors for acquiring CRAB intestinal carriage. The incidence of subsequent CRAB infection was 2.24-fold in patients with CRAB intestinal carriage compared with that in patients without (95% CI 1.48 to 3.39, p<0.001). CONCLUSION: More patients acquired CRAB intestinal carriage during their ICU stay than had on admission. Severity of illness, acute pancreatitis, tube feeding and use of carbapenems were independent risk factors of acquisition of CRAB intestinal carriage. Patients with CRAB intestinal carriage are more likely to develop CRAB infection.

The evaluation of low cut-off index values of Elecsys® HIV combi PT assay in predicting false-positive results.

OBJECTIVE: To analyze the results of different cut-off index (COI) values of Elecsys® HIV combi PT assay and to assess the role of COI in reducing the frequency of false-positive results. METHODS: We conducted a retrospective study of samples analyzed by Elecsys® HIV combi PT assay, a 4th-generation ECLIA, between 2016 and 2017. A total amount of 379 122 samples were collected for HIV (Human Immunodeficiency Virus) screening. RESULTS: A total of 379 122 samples were analyzed. 2528 (0.67%) were positive by Elecsys® HIV combi PT. Of these, 468 were false-positive results, and most of them (94.87%) were in samples with 1 < COI < 15. The false-positive rate was 0.12%. Patients with false-positive samples were more distributed in elder (P < .001) and female (P < .001) than true-positive specimens. The median COI in true-positive specimens was (385.20), which is significantly higher than false-positive specimens (2.08). The consistency between Elecsys® HIV combi PT assay and 3rd-generation and positive predictive value (PPV) increased with higher COI values. Cancer, infection, and neurological diseases were considered the potential confounding factors of HIV false-positive results (19.44%, 11.11%, and 6.62%, respectively). CONCLUSION: Samples with low COI values, especially those contain confounding factors, need to be further scrutinized to determine whether the confounding factors may cause false-positive problem. In addition, the hypothesis that low COI values may predict false-positive results is valid.

Acute HIV infection in a large teaching hospital in western China: Clinical, virological, and molecular epidemiological characteristics.

OBJECTIVE: To provide information on clinical, virological, and molecular epidemiological characteristics for early identification, diagnosis, and treatment of acute HIV infection (AHI). METHODS: A retrospective study was conducted with patients with AHI from 2012 to 2017 in West China Hospital. RESULTS: A total of 47 patients with AHI were found using a fourth-generation kit. Thirteen (27.66%) of these patients were negative if tested by third-generation tests. Median age of patients with AHI was 26 and 91.49% of them were males. Homosexual contact was responsible for 46.81% of AHI transmission. Among the individuals with AHI, 80.85% were outpatients. Common symptoms/signs were fever, headache, rash, cough and sputum, and sore throat. The syphilis coinfection rate was 17.24%. Most of the AHI was distributed in Fiebig stages IV (61.70%) and II (27.66%) with different clinical and virological characteristics. The increasing trend of cut-off index values was obvious in the course of AHI, helpful for auxiliary diagnosis. The main genetic forms of AHI were CRF07_BC and CRF01_AE, and a rare subtype CRF55_01B in Sichuan province was found. The drug resistance mutation rate was relatively high (17.65%) and five different mutations were identified. CONCLUSIONS: Fourth-generation assays are strongly recommended for screening AHI compared to third-generation ones. Different clinical and virological characteristics in different Fiebig stages were found. Young individuals and outpatients were the majority of patients with AHI and this deserves special attention. Attention should also be paid to the rare CRF55_01B in Sichuan province and surveillance of HIV resistance ought to be strengthened.

Long-Term Exposure to Ceftriaxone Sodium Induces Alteration of Gut Microbiota Accompanied by Abnormal Behaviors in Mice.

Background: Growing evidence points out that a disturbance of gut microbiota may also disturb the gut-brain communication. However, it is not clear to what extent the alteration of microbiota composition can modulate brain function, affecting host behaviors. Here, we investigated the effects of gut microbiota depletion on emotional behaviors. Methods: Mice in the experimental group were orally administered ceftriaxone sodium solution (250 mg/ml, 0.2 ml/d) for 11 weeks. The open-field test and tail-suspension test were employed for the neurobehavioral assessment of the mice. Fecal samples were collected for 16s rDNA sequencing. The serum levels of cytokines and corticosterone were quantified using enzyme-linked immunosorbent assays. The immunohistochemistry method was used for the detection of brain-derived neurotrophic factor (BDNF) and c-Fos protein. Results: The gut microbiota for antibiotic-treated mice showed lower richness and diversity compared with normal controls. This effect was accompanied by increased anxiety-like, depression-like, and aggressive behaviors. We found these changes to be possibly associated with a dysregulation of the immune system, abnormal activity of the hypothalamic-pituitary-adrenal axis, and an alteration of neurochemistry. Conclusions: The findings demonstrate the indispensable role of microbiota in the gut-brain communication and suggest that the absence of conventional gut microbiota could affect the nervous system, influencing brain function.

Wisteria floribunda agglutinin-positive Mac-2-binding protein as a diagnostic biomarker in liver cirrhosis: an updated meta-analysis.

Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+-M2BP) had been suggested as a possible glycobiomarker for assessing liver fibrosis. Here, we conducted this updated meta-analysis to systematically investigate the predictive accuracy of WFA+-M2BP for diagnosing liver fibrosis and hepatocellular carcinoma (HCC) by comparing with multiple non-invasive indicators. We searched relevant literatures from Pubmed, Web of Science, EMBASE and Cochrane Library and enrolled 36 eligible studies involving 7,362 patients. Summary results were calculated using bivariate random effects model. The pooled sensitivities, specificities and areas under the summary receiver operating characteristic curves (AUSROCs) of WFA+-M2BP for identifying mild fibrosis, significant fibrosis, advanced fibrosis, cirrhosis, and HCC were 0.70/0.68/0.75, 0.71/0.75/0.79, 0.75/0.76/0.82, 0.77/0.86/0.88, and 0.77/0.80/0.85, respectively. The accuracy of WFA+-M2BP was strongly affected by etiology and it was not better than other non-invasive indicators for predicting early fibrosis. It showed similar diagnostic performance to hyaluronic acid and FibroScan for cirrhosis, but was equivalent to α-fetoprotein for HCC. In conclusion, WFA+-M2BP was suitable to diagnose late stage of liver fibrosis, especially cirrhosis. Individual cutoff value of WFA+-M2BP could be used to grade liver fibrosis in different etiology. Combined diagnostic model was suggested to improve its predictive accuracy for HCC.

Epidemiological, clinical characteristics and drug resistance situation of culture-confirmed children TBM in southwest of China: a 6-year retrospective study.

BACKGROUND: Sichuan is a province located in southwestern China, which have a higher incidence of tuberculosis (TB). This study aimed to analyze the epidemiological and clinical characteristics, as well as drug resistance in culture-confirmed children with Tuberculosis meningitis (TBM) in Southwest of China. METHODS: We performed a retrospective study on children (< 14 years old) with cerebrospinal fluid (CSF) culture-confirmed TBM between January 2013 and December 2018 at Public Health Clinical Center of Chengdu (PHCCC). Mycobacterium tuberculosis (MTB) drug sensitivity testing (DST) was performed using the MicroDST™ method. The age, gender, family history of tuberculosis, status of Bacillus Calmette-Guérin (BCG) vaccination, residential areas information, clinical, laboratory, and radiological features were recorded. Data were analyzed using SPSS Statistics Client 25.0, and the change in drug resistance rate was examined using the Cruskal-Wallis test. RESULTS: Among 319 patients clinically diagnosed with TBM, 42 (13.2%) were Mycobacterial culture positive. Their median age was nine years, and the distribution was equal among female and male patients. Among 42 patients who were enrolled in the study, 1/42 (2.38%) passed away. Children with TBM were concentrated in the minority areas of western Sichuan, where 34/42 (81.0%) patients with TBM belonged to ethnic minorities, and only 2/42 (4.76%) received BCG vaccination in the past. Chest X-rays changes were observed in all patients. Fever and headache were the most common presenting symptom. Thirty-five (83.3%) patients suffered from neck stiffness, and 30/42 (71.4%) had high CSF pressure. DST results showed that the resistance rate was high; resistance to any anti-tuberculosis drug (ATD) was observed in 13 (31.0%) patient isolates, while multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) were found in 2 (4.8%) and 1 (2.4%) patients, respectively. CONCLUSIONS: TBM among children in Southwest China was mainly concentrated in the minority areas of western Sichuan and more than 95% of patients did not receive BCG vaccination at birth. The most common symptoms were fever, headache, and neck stiffness and all patients had positive chest X-ray findings. In addition, high rates of drug resistance were found.