Nobiletin Regulates Polyinosinic-polycytidylic Acid-induced Inflammation in Macrophages Partially via the PPAR-γ Signaling Pathway.

INTRODUCTION: Macrophage dysregulation is a common pathogenic feature of viruses that provides extensive targets for antiviral therapy. Nobiletin, a polymethoxylated flavonoid found in citrus fruits, has a multitude of effects. METHODS: We investigated the effect of nobiletin on polyinosinic-polycytidylic acid (poly(I:C))-induced inflammation in RAW264.7 cells. Nobiletin inhibited the production of poly(I:C)-induced inflammatory factors, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, and CXCL10. High-throughput sequencing revealed that nobiletin inhibited the expression of TNF-α, IL-6, and CXCL10 and promoted the expression of CD206, Chil3, and Vcam1. In the Kyoto Encyclopedia of Genes and Genomes enrichment analyses, the upregulated differential genes were significantly enriched in the peroxisome proliferator-activated receptor (PPAR) signaling pathway. RESULTS: The PPAR-γ inhibitor T0070907 significantly reversed the inhibitory effects of nobiletin on IL-6 and CXCL10 but had no significant effect on TNF-α secretion. CONCLUSION: Thus, nobiletin regulated poly(I:C)-induced inflammatory responses in RAW264.7 cells partially via the PPAR-γ signaling pathway.

Bilirubin influences the predictive effect of body mass index on hospital mortality in critically ill patients.

Introduction: Body mass index (BMI) can predict mortality in critically ill patients. Moreover, mortality is related to increased bilirubin levels. Thus, herein, we aimed to investigate the effect of bilirubin levels on the usefulness of BMI in predicting mortality in critically ill patients. Methods: Data were extracted from the Medical Information Mart for Intensive Care (MIMIC IV) database. Patients were divided into two groups according to their total bilirubin levels within 24 h. Cox proportional hazard regression models were applied to obtain adjusted hazard ratios and 95 % confidence intervals for the correlation between BMI categories and hospital mortality. The dose-response relationship was flexibly modeled using a restricted cubic spline (RCS) with three knots. Results: Of the 14376 patients included, 3.4 % were underweight, 29.3 % were of normal body weight, 32.2 % were overweight, and 35.1 % were obese. For patients with total bilirubin levels <2 mg/dL, hospital mortality was significantly lower in patients with obesity than in normal body weight patients (p < 0.05). However, the opposite results were observed for patients with total bilirubin levels ≥2 mg/dL. The Cox proportional hazard regression models suggested that the risk of death was lower in patients with overweightness and obesity than in normal body weight patients when the total bilirubin levels were <2 mg/dL, but not in the other case (total bilirubin levels ≥2 mg/dL). RCS analyses showed that, for patients with total bilirubin levels <2 mg/dL, the risk of death gradually decreased with increasing BMI. Conversely, for patients with total bilirubin levels ≥2 mg/dL, this risk did not decrease with increasing BMI until reaching obesity, after which it increased rapidly. Conclusion: BMI predicted the risk of death differently in critically ill patients with different bilirubin levels.

Study on relationship of target organ injury of mechanism and "structure-effect-dose" of Hedysari Radix during radiotherapy-chemotherapy induced / 中国药理学通报

Aim To explore the possible mechanism of "component-target-pathway" of Radix Hedysari against target organ damage caused by radiotherapy and chemotherapy, and to verify the " dose-effect" relationship of the main active components. Methods TCMSP, Uniprot, Swiss Target Prediction, GeneCards, Cytoscape, Omicshare and other platforms were used for network pharmacology analysis. Autodock, Pymol and Ligplot were used for molecular docking. The water extract of Radix Hedysari was used for animal experiment verification. The contents of eight main components were determined by HPLC. Results Four active components, eight key targets and four key pathways of Radix Hedysari were identified to resist the damage of target organs caused by radiotherapy and chemotherapy. Molecular docking showed that formononetin and quercetin had good binding activity with HSP90AA1, naringenin and MAPK3, and ursolic acid and TP53. Animal experiments showed that gastrointestinal factors MTL and VIP increased significantly, liver and kidney factors Cr, BUN, AST and ALT decreased significantly, inflammatory factor IL-10 increased significantly and TNF-a decreased significantly. The content of ononm was the highest (2 . 884 8 µg • g "

The effect of high-power atrial fibrillation ablation on intraoperative acute pulmonary vein isolation and postoperative troponin levels / 中国医师杂志

Objective:To compare the effects of high-power and conventional power atrial fibrillation ablation on intraoperative acute pulmonary vein isolation, postoperative troponin levels, and atrial fibrillation recurrence.Methods:A retrospective selection was conducted on 105 patients with paroxysmal atrial fibrillation admitted to the Baoding NO.1 Central Hospital from January 2017 to December 2020. According to different treatment methods, they were divided into a high-power ablation group of 52 cases and a conventional power ablation group of 53 cases. The intraoperative rate of single circle acute pulmonary vein isolation, the recovery of electrical conduction after acute pulmonary vein isolation, and the location and number of points that need to be added were compared between the two groups; At the same time, two groups were compared in terms of surgical time, ablation time, surgical radiation exposure time and radiation dose, intraoperative complications postoperative cardiac troponin levels at 12 hours, and recurrence of atrial fibrillation within 1 year after ablation.Results:The intraoperative single loop pulmonary vein isolation rate and postoperative troponin levels in the high-power atrial fibrillation ablation group were higher than those in the conventional atrial fibrillation ablation group (all P<0.05). The surgical time, ablation time, and the number of sites and points that need to be added during surgery were less than those in the conventional atrial fibrillation ablation group (all P<0.05). There was no statistically significant difference in the incidence of intraoperative complications and postoperative atrial fibrillation recurrence between the two groups (all P>0.05). Conclusions:High power atrial fibrillation ablation has a higher single loop acute pulmonary vein isolation rate, fewer patch sites and points, shorter surgical time, and greater ablation damage compared to conventional ablation, and the clinical efficacy of the two groups is similar after surgery.

4-Octyl itaconate inhibits poly(I:C)-induced interferon-ß secretion in mouse bone marrow-derived macrophages partially by activating Nrf2.

Viruses have become a major threat to human health. Interferon-ß (IFN-ß) has a key role in the antivirus process, as it can increase the expression of antivirus-associated genes. Itaconate and its derivatives can regulate the immune response, secretion of inflammatory factors, and pyroptosis of macrophages. The effect of itaconate on IFN-ß secretion of double-stranded RNA-induced macrophages are not well known. A derivative of itaconate, 4-octoyl itaconate (4-OI), was used to treat mouse bone marrow-derived macrophages (BMDM) induced with 100 µg/mL poly(I:C). The IFN-ß concentration was detected through ELISA, and IFN-ß mRNA expression was detected through quantitative PCR. High-throughput transcriptome sequencing was used to analyze changes in the BMDM transcriptome after 4-OI treatment. The Nrf2 expression was knocked down with siRNA.4-OI inhibited poly(I:C)-induced IFN-ß secretion and mRNA expression in BMDM. Results of transcriptome sequencing revealed that 4-OI downregulated 1047 genes and upregulated 822 genes. GO and KEGG enrichment of differently expressed genes revealed that many downregulated genes were related to the anti-virus process, whereas many upregulated genes were related to metabolism. The Nrf2 inhibitor ML385 and Nrf2 siRNA could partially reverse the inhibitory effect of 4-OI. In conclusion, 4-octyl itaconate could inhibit the poly(I:C)-induced interferon-ß secretion in BMDM partially by regulating Nrf2.

Therapeutic efficacy of liraglutide versus metformin in modulating the gut microbiota for treating type 2 diabetes mellitus complicated with nonalcoholic fatty liver disease.

Metformin and liraglutide are used in the treatment of type 2 diabetes mellitus (T2DM) complicated with nonalcoholic fatty liver disease (NAFLD). Although these drugs can alter the intestinal microbiome, clinical data are required to explore their mechanisms of action. Using 16S sequencing technology, we analyzed and compared the intestinal bacterial community structure and function between patients before and after treatment (12 weeks) with the two drugs (metformin or liraglutide, n = 15) and healthy controls (n = 15). Moreover, combined with 19 clinical indices, the potential therapeutic mechanisms of the two drugs were compared. The studied clinical indices included those associated with islet ß-cell function (FPG, FINS, HbA1c, and HOMA-IR), inflammation (TNF-α, IL-6, and APN), lipid metabolism (TC, TG, and LDL-C), and liver function (ALT, AST, and GGT); the values of all indices changed significantly after treatment (p < 0.01). In addition, the effect of the two drugs on the intestinal bacterial community varied. Liraglutide treatment significantly increased the diversity and richness of the intestinal bacterial community (p < 0.05); it significantly increased the relative abundances of Bacteroidetes, Proteobacteria, and Bacilli, whereas metformin treatment significantly increased the relative abundance of Fusobacteria and Actinobacteria (p < 0.05). Metformin treatment increased the complexity and stability of the intestinal bacterial network. However, liraglutide treatment had a weaker effect on the intestinal bacterial network, and the network after treatment was similar to that in healthy controls. Correlation matrix analysis between dominant genera and clinical indicators showed that the correlation between the bacterial community and islet ß-cell function was stronger after liraglutide treatment, whereas the correlation between the bacterial community and inflammation-related factors was stronger after metformin treatment. Functional prediction showed that liraglutide could significantly affect the abundance of functional genes related to T2DM and NAFLD (p < 0.05), but the effect of metformin was not significant. This study is the first to report the changes in the intestinal bacterial community in patients treated with metformin or liraglutide and the differences between the mechanisms of action of metformin and liraglutide. Metformin or liraglutide has a therapeutic value in T2DM complicated with NAFLD, with liraglutide having a weaker effect on the intestinal bacterial community but a better therapeutic efficacy.

Confusion and countermeasures of the non-conditioned anxiety test in rodent laboratory animals / 中华行为医学与脑科学杂志

Anxiety is a major mood disorder, and the high morbidity, co-morbidity and disability of anxiety disorders seriously affect people's quality of life, so the importance and urgency of research on anxiety cannot be overstated. Animal models are the main carriers for studying the mechanism of disease occurrence and development, drug efficacy evaluation and drug development.Unconditioned anxiety model is a common anxiety model.Elevated plus maze test, open field test and light-dark box test are widely accepted paradigms for the detection of unconditioned anxiety.This kind of behavioral paradigm based on environmental exposure takes advantage of the conflict between curiosity and fear of the unfamiliar environment to simulate and detect the anxiety of animals.However, the validity of these behavioral paradigms for evaluating anxiety in animals is questionable.In this paper, we discuss the concept of anxiety, the definition of anxiety behavior in the behavioral test of unconditioned anxiety, and the factors to be considered in the test of unconditioned anxiety behavior.On this basis, new solutions were proposed to the contradictions and blind spots in order to improve the test paradigm of anxiety behavior and provide a more reliable animal model for the evaluation of anxiety.This paper presents a new approach to address the contradictions and blind spots of this paradigm.

A multi-center study on evaluation of leukocyte differential performance by an artificial intelligence-based Digital Cell Morphology Analyzer / 中华检验医学杂志

Objective:To evaluate the performance of an artificial intelligent (AI)-based automated digital cell morphology analyzer (hereinafter referred as AI morphology analyzer) in detecting peripheral white blood cells (WBCs).Methods:A multi-center study. 1. A total of 3010 venous blood samples were collected from 11 tertiary hospitals nationwide, and 14 types of WBCs were analyzed with the AI morphology analyzers. The pre-classification results were compared with the post-classification results reviewed by senior morphological experts in evaluate the accuracy, sensitivity, specificity, and agreement of the AI morphology analyzers on the WBC pre-classification. 2. 400 blood samples (no less than 50% of the samples with abnormal WBCs after pre-classification and manual review) were selected from 3 010 samples, and the morphologists conducted manual microscopic examinations to differentiate different types of WBCs. The correlation between the post-classification and the manual microscopic examination results was analyzed. 3. Blood samples of patients diagnosed with lymphoma, acute lymphoblastic leukemia, acute myeloid leukemia, myelodysplastic syndrome, or myeloproliferative neoplasms were selected from the 3 010 blood samples. The performance of the AI morphology analyzers in these five hematological malignancies was evaluated by comparing the pre-classification and post-classification results. Cohen′s kappa test was used to analyze the consistency of WBC pre-classification and expert audit results, and Passing-Bablock regression analysis was used for comparison test, and accuracy, sensitivity, specificity, and agreement were calculated according to the formula.Results:1. AI morphology analyzers can pre-classify 14 types of WBCs and nucleated red blood cells. Compared with the post-classification results reviewed by senior morphological experts, the pre-classification accuracy of total WBCs reached 97.97%, of which the pre-classification accuracies of normal WBCs and abnormal WBCs were more than 96% and 87%, respectively. 2. The post-classification results reviewed by senior morphological experts correlated well with the manual differential results for all types of WBCs and nucleated red blood cells (neutrophils, lymphocytes, monocytes, eosinophils, basophils, immature granulocytes, blast cells, nucleated erythrocytes and malignant cells r>0.90 respectively, reactive lymphocytes r=0.85). With reference, the positive smear of abnormal cell types defined by The International Consensus Group for Hematology, the AI morphology analyzer has the similar screening ability for abnormal WBC samples as the manual microscopic examination. 3. For the blood samples with malignant hematologic diseases, the AI morphology analyzers showed accuracies higher than 84% on blast cells pre-classification, and the sensitivities were higher than 94%. In acute myeloid leukemia, the sensitivity of abnormal promyelocytes pre-classification exceeded 95%. Conclusion:The AI morphology analyzer showed high pre-classification accuracies and sensitivities on all types of leukocytes in peripheral blood when comparing with the post-classification results reviewed by experts. The post-classification results also showed a good correlation with the manual differential results. The AI morphology analyzer provides an efficient adjunctive white blood cell detection method for screening malignant hematological diseases.

Antifungal susceptibility profiles and drug resistance mechanisms of clinical Candida duobushaemulonii isolates from China.

Candida duobushaemulonii, type II Candida haemulonii complex, is closely related to Candida auris and capable of causing invasive and non-invasive infections in humans. Eleven strains of C. duobushaemulonii were collected from China Hospital Invasive Fungal Surveillance Net (CHIF-NET) and identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF), VITEK 2 Yeast Identification Card (YST), and internal transcribed spacer (ITS) sequencing. Whole genome sequencing of C. duobushaemulonii was done to determine their genotypes. Furthermore, C. duobushaemulonii strains were tested by Sensititre YeastOne™ and Clinical and Laboratory Institute (CLSI) broth microdilution panel for antifungal susceptibility. Three C. duobushaemulonii could not be identified by VITEK 2. All 11 isolates had high minimum inhibitory concentrations (MICs) to amphotericin B more than 2 µg/ml. One isolate showed a high MIC value of ≥64 µg/ml to 5-flucytosine. All isolates were wild type (WT) for triazoles and echinocandins. FUR1 variation may result in C. duobushaemulonii with high MIC to 5-flucytosine. Candida duobushaemulonii mainly infects patients with weakened immunity, and the amphotericin B resistance of these isolates might represent a challenge to clinical treatment.

The transcription activator AtxA from Bacillus anthracis was employed for developing a tight-control, high-level, modulable and stationary-phase-specific transcription activity in Escherichia coli.

The strong transcriptional activity of the virulent gene pagA in Bacillus anthracis has been proven to be anthrax toxin activator (AtxA)-regulated. However, the obscure pagA transcription mechanism hinders practical applications of this strong promoter. In this study, a 509-bp DNA fragment [termed 509sequence, (-508)-(+1) relative to the P2 transcription start site] was cloned upstream of rbs-GFPuv as pTOL02B to elucidate the AtxA-regulated transcription. The 509sequence was dissected into the -10 sequence, -35 sequence, ATrich tract, SLI/SLII and upstream site. In conjunction with the heterologous co-expression of AtxA (under the control of the T7 promoter), the -10 sequence (TATACT) was sufficient for the AtxA-regulated transcription. Integration of pTOL02F + pTOLAtxA as pTOL03F showed that the AtxA-regulated transcription exhibited a strong specific fluorescence intensity/common analytical chemistry term (OD600) of 40 597 ± 446 and an induction/repression ratio of 122. An improved induction/repression ratio of 276 was achieved by cultivating Escherichia coli/pTOL03F in M9 minimal medium. The newly developed promoter system termed PAtxA consists of AtxA, the -10 sequence and Escherichia RNA polymerase. These three elements synergistically and cooperatively formed a previously undiscovered transcription system, which exhibited a tight-control, high-level, modulable and stationary-phase-specific transcription. The PAtxA was used for phaCAB expression for the stationary-phase polyhydroxybutyrate production, and the results showed that a PHB yield, content and titer of 0.20 ± 0.27 g/g-glucose, 68 ± 11% and 1.5 ± 0.4 g/l can be obtained. The positive inducible PAtxA, in contrast to negative inducible, should be a useful tool to diversify the gene information flow in synthetic biology. Graphical Abstract.

Persistence of an epidemic cluster of Rhodotorula mucilaginosa in multiple geographic regions in China and the emergence of a 5-flucytosine resistant clone.

Rhodotorula mucilaginosa, an environmental yeast widely used in industry and agriculture, is also an opportunistic pathogen resistant to multi-antifungals. During the national surveillance in China, R. mucilaginosa has been documented from various hospitals and regions. At present, the molecular epidemiology of invasive infections caused by R. mucilaginosa and their resistance profiles to antifungals were unknown. Here we collected 49 strains from four hospitals located in different geographic regions from 2009 to 2019 in China, determined their genotypes using different molecular markers and quantified susceptibilities to various antifungals. Sequencing of ITS and D1/D2 regions in rDNA indicated that 73.5% (36/49) of clinical strains belong to same sequence type (rDNA type 2). Microsatellite (MT) genotyping with 15 (recently developed) tandem repeat loci identified 5 epidemic MT types, which accounted for 44.9% (22/49) of clinical strains, as well as 27 sporadic MT types. Microsatellite data indicated that the presence of an epidemic cluster including 35 strains (71.4%) repeatedly isolated in four hospitals for eight years. Single nucleotide variants (SNVs) from the whole genome sequence data also supported the clustering of these epidemic strains due to low pairwise distance. In addition, phylogenetic analysis of SNVs from these clinical strains, together with environmental and animal strains showed that the closely related epidemic cluster strains may be opportunistic, zoonotic pathogens. Also, molecular data indicated a possible clonal transmission of pan echinocandins-azoles-5-flucytosine resistant R. mucilaginosa strains in hospital H01. Our study demonstrated that R. mucilaginosa is a multi-drug resistant pathogen with the ability to cause nosocomial infection.

Mild Traumatic Brain Injury in Elderly Patients Receiving Direct Oral Anticoagulants: A Systematic Review and Meta-Analysis.

The aim of this work was to conduct a systematic review and meta-analysis of studies reporting on the risk of traumatic intracerebral hemorrhage (tICH), the course of tICH, and its treatment and mortality rates in elderly mild traumatic brain injury (mTBI) patients using direct oral anticoagulants (DOACs). We consulted PubMed and Embase for relevant cohort and case-control studies with a control group. Two authors independently selected studies, assessed methodological quality, and extracted outcome data. Estimates were pooled with the Mantel-Haenszel random-effects method. We identified 16 articles comprising 3671 elderly mTBI patients using DOACs. Use of DOACs was associated with a reduced risk of tICH compared to the use of vitamin K antagonists (VKAs; odds ratio [OR], 0.44; 95% confidence interval [CI], 0.29-0.65; I2 = 22%) and a similar risk compared to the use of antiplatelet therapy (APT; OR, 0.98; 95% CI, 0.39-2.44; I2 = 0%). Reversal agent use and neurosurgical intervention rate were lower in patients using DOACs compared to patients using VKAs (OR, 0.10; 95% CI, 0.06-0.16; I2 = 0% and OR, 0.37; 95% CI, 0.21-0.67; I2 = 0%, respectively). There was no significant difference in neurosurgical intervention rate between patients who used DOACs versus patients who used APT (OR, 0.58; 95% CI, 0.15-2.21; I2 = 41%) or no antithrombotic therapy (OR, 0.76; 95% CI, 0.20-2.86; I2 = 23%). ICH progression, risk of delayed ICH, and TBI-related in-hospital mortality were comparable among treatment groups. The present study indicates that elderly patients using DOACs have a lower risk of adverse outcome compared to patients using VKAs and a similar risk compared to patients using APT after mTBI.

Analysis of Cross-Reactivity and Allergic Symptoms of 19 Allergens: Results from NHANES 2005-2006.

INTRODUCTION: We explored the cross-reactivity among 19 common allergen sources and evaluated the influence of serum IgE concentrations and the number of sensitized allergens on the incidence of allergic symptoms. METHODS: We conducted this cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES) 2005-2006 which is a program of studies designed to assess the health and nutritional status of adults and children in the USA. After excluding participants with missing data from the allergen IgE test, allergy questionnaire, and respiratory health questionnaire, a total of 7,224 participants aged 6 years and older were included, as children younger than 6 years old did not complete all 19 allergen-specific IgE tests. Spearman correlation analysis was used to analyze the cross-reactivity between allergen sources. An independent sample Kruskal-Wallis test was performed to investigate the relationship between the serum-specific IgE levels of 19 allergens and the incidence of allergic symptoms. RESULTS: The cross-reactivity between D. farinae and D. pteronyssinus was the strongest (ρ = 0.88), and cross-reactivity of cross-species was universal. With the increase in serum-specific IgE levels of D. farinae, D. pteronyssinus, oak, and birch, the incidence of sneezing increased (p < 0.05). With the increase in serum-specific IgE levels of cats, dogs, peanuts, Aspergillus, and Alternaria, the incidence of wheezing increased (p < 0.05). The incidence of rash was positively correlated with serum-specific IgE levels of D. farinae, D. pteronyssinus, shrimp, and peanut (p < 0.05). The incidence of wheezing continued to increase with an increase in sensitized allergens. When participants were sensitized to <10 allergens, the incidence of sneezing continued to increase as the number of sensitized allergens increased, whereas the incidence of rash did not have a clear association with the number of sensitized allergens. CONCLUSION: Species that are biologically close are more likely to have antigen cross-reactivity, while cross-reactivity among different species is common. Different allergens tend to cause different allergic symptoms. Different allergic sites in the body have inconsistent responses to the number of sensitized allergens.

Optimization of the detection method for urine S-phenylmercapturic acid via modified performance liquid chromatography-mass spectrometry / 中国职业医学

@#Objective - To optimize the extraction and quantification methods for the determination of S phenylmercapturic acid - Methods (SPMA) in urine with performance liquid chromatography mass spectrometry. The urine was hydrolyzed with 50.0% sulfuric acid. The hydrolysate was purified by solid phase extraction column. Purified samples were separated by C18 chromatographic column and detected by tandem mass spectrometry. The isotope labeled SPMA was used as the internal Results - standard. The internal standard curve was used for quantification. The linear range of SPMA was 0.50 50.00 μg/L with the correlation coefficient of 0.999 8. The detection limit and the lower limit of quantification were 0.05 and 0.17 μg/L, - - - - respectively. The recovery rate was 97.0% 102.0%. The within run and between run relative standard deviation were 0.6% 1.0% - and 1.7% 6.5%, respectively. The mass concentration of urinary SPMA in the occupational benzene exposure group was - vs P higher than the non occupational benzene exposure group by this method (median: 2.81 0.28 μg/g creatinine, <0.05). Conclusion Compared to the national standard method, this optimized method of solid phase extraction and internal standard for quantification eliminates the matrix effect. This method is accurate and precise, and is suitable for the determination of SPMA acid in urine.

HIV-1 genetic characteristics and drug resistance in newly diagnosed population in Baoding city of Hebei Province / 中华微生物学和免疫学杂志

Objective:To investigate the distribution of HIV-1 genotypes and drug resistance in newly diagnosed HIV-1 patients in Baoding in 2020.Methods:A self-developed method was used to amplify the pol gene sequence of HIV-1, and the sequencing results were analyzed by phylogenetic analysis and compared with the Stanford drug resistance database to determine the HIV-1 subtypes and gene mutations. Results:A total of 96 patients with HIV-1 infection were recruited in this study, and 83 pol gene sequences were successfully obtained. In the study population, 88 (91.7%) were male with an average age of 39 years and 54 (56.3%) were married. Most of the patients were infected through sexual contact (95.8%, 92/96), and 75.0% (72/96) were through homosexual transmission. Phylogenetic analysis showed that various HIV-1 subtypes were detected and among them, CRF01_AE (51.8%, 43/83), CRF07_BC (24.1%, 20/83) and B subtype (10.8%, 9/83) were the most epidemic strains. Moreover, the subtypes of newly identified recombinant strains in recent years accounted for 13.3% (11/83). Drug resistance test results showed that the pre-treatment drug resistance rate in newly diagnosed HIV-1 patients was 8.4% (7/83), and the drug resistance rates to protease inhibitor (PIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and integrase inhibitors (INIs) were 3.6% (3/83), 1.2% (1/83) and 3.6% (3/83), respectively. Conclusions:The HIV-1 subtypes in the newly diagnosed population in Baoding in 2020 were complex and diverse. There were many unique recombinant strains and drug-resistant strains. Therefore, it was necessary to strengthen drug resistance monitoring as well as the prevention and control of HIV-1 infection in this area.

Strategies of endovascular recanalization in acute vertebrobasilar artery occlusion of different lesion sites: a comparative analysis / 中华神经医学杂志

Objective:To investigate the pathogenesis, selection of endovascular treatment (EVT) strategies, and efficacies of acute vertebrobasilar artery occlusion (AVBAO) of different lesion sites.Methods:One hundred and five patients with AVBAO, admitted to and accepted EVT in our hospital from February 2017 to September 2019, were chosen in our study. The data of disease onset, imaging findings, EVT status, perioperative complications, and prognoses of these patients were collected. According to DSA results, the involved lesions were divided into 4 sites: the upper segment of basilar artery (BA), the middle segment of BA, the lower segment of BA, and the intracranial segment of vertebral artery (V4 segment), and patients with tandem lesions would be recorded as distal lesions. The risk factors, EVT strategies, and prognoses 90 d after follow-up (modified Rankin scale [mRS] scores≤3: good prognosis) were compared in patients with 4 different lesion sites.Results:There were significant differences in etiological classifications and percentage of patients combined with atrial fibrillation among patients with 4 different lesion sites ( P<0.05). There was significant difference in proportion of patients accepted emergency stent implantation among patients with 4 different lesion sites ( P<0.05): those with lesions at the V4 segment had the highest proportion of patients accepted emergency stent implantation (79.55%), followed by those with lesions at the lower segment of BA (50.00%). There was significant difference in EVT time (the time from arterial puncture to successful recanalization of occluded vessels) among patients with 4 different lesion sites ( P<0.05): the EVT time in patients with lesions at the middle segment of BA was the shortest (87.5 [58.5, 130.8] min), and the EVT time in patients with lesions at the lower segment of BA was the longest (115.0 [81.0, 163.0] min). There was no statistical difference among patients with different lesion sites in good prognosis rate 90 d after follow-up ( P>0.05). Conclusion:The pathogenesis of patients with different AVBAO lesion sites is different, so different EVT strategies should be adopted.

Values of arterial spin labeling in evaluating blood-brain barrier permeability in cerebral infarction lesions and predicting hemorrhage transformation after endovascular recanalization / 中华神经医学杂志

Objective:To assess the role of arterial spin labeling (ASL) in detecting the blood-brain barrier (BBB) permeability of cerebral infarction lesions in patients with anterior circulation subacute ischemic stroke (SIS), and to evaluate the value of ASL in predicting hemorrhagic transformation (HT) of SIS patients after endovascular recanalization.Methods:A prospective analysis was performed. Patients with anterior circulation SIS who received endovascular treatment (EVT) in our hospital from January 2021 to September 2021 were enrolled. At 24 h before EVT and immediately after EVT, MRI scans of ASL sequences and dynamic contrast-enhanced magnetic resonance (DCE) sequence were completed, and Xper CT was performed; accordingly, imaging typing was performed. Head CT scan was performed 24-48 h after EVT to observe HT; according to the presence or absence of HT, these patients were divided into HT group and non-HT group; the relative cerebral blood flow (rCBF) values of ASL sequence parameters, volume transfer constant (K trans) of DCE sequence parameters and the differences of ASL, DCE and Xper CT imaging types between the two groups were compared. The weighted Kappa coefficient was used to test the consistency among ASL, DCE and Xper CT imaging types. Results:Among 22 eligible patients, 5 patients occurred HT (5/22, 22.72%). As compared with those in the non-HT group (1.14±0.04; 0.032[0.024, 0.039]/min), patients in the HT group had significantly higher rCBF value (1.57±0.18) and K trans (0.072[0.0455, 0.117]/min, P<0.05). There were significant differences in the distribution of ASL, DCE and Xper CT imaging types between the two groups ( P<0.05); among them, 4 out of 6 patients with ASL imaging type III, 4 out of 6 patients with DCE imaging type III, and 4 out of 5 patients with Xper CT imaging type III had HT. ASL sequence and DCE sequence had a high consistency in the imaging types (Kappa coefficient=0.941, 95%CI: 0.862-1.020, P<0.001). Conclusion:ASL can effectively evaluate the BBB permeability of cerebral infarction lesions in patients with anterior circulation SIS; patients with ASL imaging type III have a relatively high risk of HT.

Values of arterial spin labeling in evaluating blood-brain barrier permeability in cerebral infarction lesions and predicting hemorrhage transformation after endovascular recanalization / 中华神经医学杂志

Objective:To assess the role of arterial spin labeling (ASL) in detecting the blood-brain barrier (BBB) permeability of cerebral infarction lesions in patients with anterior circulation subacute ischemic stroke (SIS), and to evaluate the value of ASL in predicting hemorrhagic transformation (HT) of SIS patients after endovascular recanalization.Methods:A prospective analysis was performed. Patients with anterior circulation SIS who received endovascular treatment (EVT) in our hospital from January 2021 to September 2021 were enrolled. At 24 h before EVT and immediately after EVT, MRI scans of ASL sequences and dynamic contrast-enhanced magnetic resonance (DCE) sequence were completed, and Xper CT was performed; accordingly, imaging typing was performed. Head CT scan was performed 24-48 h after EVT to observe HT; according to the presence or absence of HT, these patients were divided into HT group and non-HT group; the relative cerebral blood flow (rCBF) values of ASL sequence parameters, volume transfer constant (K trans) of DCE sequence parameters and the differences of ASL, DCE and Xper CT imaging types between the two groups were compared. The weighted Kappa coefficient was used to test the consistency among ASL, DCE and Xper CT imaging types. Results:Among 22 eligible patients, 5 patients occurred HT (5/22, 22.72%). As compared with those in the non-HT group (1.14±0.04; 0.032[0.024, 0.039]/min), patients in the HT group had significantly higher rCBF value (1.57±0.18) and K trans (0.072[0.0455, 0.117]/min, P<0.05). There were significant differences in the distribution of ASL, DCE and Xper CT imaging types between the two groups ( P<0.05); among them, 4 out of 6 patients with ASL imaging type III, 4 out of 6 patients with DCE imaging type III, and 4 out of 5 patients with Xper CT imaging type III had HT. ASL sequence and DCE sequence had a high consistency in the imaging types (Kappa coefficient=0.941, 95%CI: 0.862-1.020, P<0.001). Conclusion:ASL can effectively evaluate the BBB permeability of cerebral infarction lesions in patients with anterior circulation SIS; patients with ASL imaging type III have a relatively high risk of HT.

Evaluation for the performance of HIV Ag/Ab assay based on ECLIA in blood screening / 中国输血杂志

【Objective】 To evaluate the performance of electrochemiluminescence immunoassay (ECLIA) in detecting HIV antigen/antibody in blood screening. 【Methods】 A total of 128 donors, reactive to anti-HIV(ELISA)testing, from September 2016 to September 2020 were enrolled, and seven samples were reactive to double anti-HIV reagents, among which 6 were confirmed by WB, 1 confirmed by NAT as negative.Two group of donors, reactive to solo anti-HIV reagent but being confirmed negative by WB(n=121) vs.randomly selected donors non-reactive to ELISA + NAT(June to September 2020, n=1360), were subjected to HIV antigen/antibody testing using ECLIA to compare the testing results, including concordance rate, sensitivity and specificity. 【Results】 The ECLIA results remained non-reactive for 1360 samples initially non-reactive to both ELISA and NAT.The concordance rate of anti-HIV reactivity by ECLIA and ELISA+ WB were 100%(6/6). For 122 samples, reactive to ELISA anti-HIV testing but nonreactive to confirmatory testing, 4(3.28%)of them were reactive to HIV antigen/antibody testing and 118(96.72%) nonreactive, with the concordance rate of ECLIA and ELISA at 96.88%(124/128). The sensitivity, specificity and false positive rate of ECLIA and ELISA were 100% vs 100%, 99.73% vs 91.77%, and 0.27% vs 8.23%, respectively. 【Conclusion】 ECLIA for HIV antigen/antibody detection has good sensitivity and specificity, which can meet the requirements of blood screening, and the false positive rate is lower than that of ELISA, adopted commonly in blood bank at present.

Antifungal Susceptibility Profiles and Resistance Mechanisms of Clinical Diutina catenulata Isolates With High MIC Values.

Diutina catenulata (Candida catenulata) is an ascomycete yeast species widely used in environmental and industrial research and capable of causing infections in humans and animals. At present, there are only a few studies on D. catenulata, and further research is required for its more in-depth characterization and analysis. Eleven strains of D. catenulata collected from China Hospital Invasive Fungal Surveillance Net (CHIF-NET) and the CHIF-NET North China Program were identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry and internal transcribed spacer sequencing. The antifungal susceptibility of the Diutina catenulata strains was tested using the Clinical and Laboratory Standards Institute broth microdilution method and Sensititre YeastOne™. Furthermore, ERG11 and FKS1 were sequenced to determine any mutations related to azole and echinocandin resistance in D. catenulata. All isolates exhibited low minimum inhibitory concentration (MIC) values for itraconazole (0.06-0.12 µg/ml), posaconazole (0.06-0.12 µg/ml), amphotericin B (0.25-1 µg/ml), and 5-flucytosine (range, <0.06-0.12 µg/ml), whereas four isolates showed high MICs (≥4 µg/ml) for echinocandins. Strains with high MIC values for azoles showed common ERG11 mutations, namely, F126L/K143R. In addition, L139R mutations may be linked to high MICs of fluconazole. Two amino acid alterations reported to correspond to high MIC values of echinocandin, namely, F621I (F641) and S625L (S645), were found in the hot spot 1 region of FKS1. In addition, one new amino acid alteration, I1348S (I1368), was found outside of the FKS1 hot spot 2 region, and its contribution to echinocandin resistance requires future investigation. Diutina catenulata mainly infects patients with a weak immune system, and the high MIC values for various antifungals exhibited by these isolates may represent a challenge to clinical treatment.