IGF2BP3 modified GLI2 transcriptionally regulates SYVN1 and facilitates sepsis liver injury through autophagy.

Autophagy enhancement in septic liver injury can play a protective role. Nerveless, the mechanism of autophagy-mediated septic liver injury needs further investigation. Our study demonstrated that in septic condition, GLI Family Zinc Finger 2 (GLI2) was elevated, whereas peroxisome-proliferator-activated receptor α (PPARα) was downregulated. Suppressing GLI2 or synovialapoptosis inhibitor 1 (SYVN1) in LPS-exposed cells increased PPARα levels, enhanced cell viability and autophagy, while inhibiting apoptosis. LPS enhanced the GLI2-SYVN1 promoter binding. SYVN1 fostered ubiquitin-mediated degradation of PPARα. IGF2BP3 stabilized GLI2 mRNA by targeting its m6A site. Silencing IGF2BP3 led to decreased GLI2 and SYVN1 but increased PPARα levels, promoting cell survival and autophagy, while repressing apoptosis. This was counteracted by SYVN1 overexpression. In cecal ligation and puncture mice, IGF2BP3, SYVN1, or GLI2 knockdown ameliorated liver damage and augmented autophagy. In summary, IGF2BP3 enhanced GLI2 stability, overexpressed GLI2 subsequent promoted SYVN1 levels by interacting with its promoter, leading to ubiquitinated degradation of PPARα, thereby inhibiting PPARα-mediated autophagy and then exacerbating liver injury in sepsis.

Cervical cancer biomarker screening based on Raman spectroscopy and multivariate statistical analysis.

Cervical cancer (CC) stands as one of the most prevalent malignancies among females, and the examination of serum tumor markers(TMs) assumes paramount significance in both its diagnosis and treatment. This research delves into the potential of combining Surface-Enhanced Raman Spectroscopy (SERS) with Multivariate Statistical Analysis (MSA) to diagnose cervical cancer, coupled with the identification of prospective serum biomarkers. Serum samples were collected from 95 CC patients and 81 healthy subjects, with subsequent MSA employed to analyze the spectral data. The outcomes underscore the superior efficacy of Partial Least Squares Discriminant Analysis (PLS-DA) within the MSA framework, achieving predictive accuracy of 97.73 %, and exhibiting sensitivities and specificities of 100 % and 95.83 % respectively. Additionally, the PLS-DA model yields a Variable Importance in Projection (VIP) list, which, when coupled with the biochemical information of characteristic peaks, can be utilized for the screening of biomarkers. Here, the Random Forest (RF) model is introduced to aid in biomarker screening. The two findings demonstrate that the principal contributing features distinguishing cervical cancer Raman spectra from those of healthy individuals are located at 482, 623, 722, 956, 1093, and 1656 cm-1, primarily linked to serum components such as DNA, tyrosine, adenine, valine, D-mannose, and amide I. Predictive models are constructed for individual biomolecules, generating ROC curves. Remarkably, D-mannose of V (C-N) exhibited the highest performance, boasting an AUC value of 0.979. This suggests its potential as a serum biomarker for distinguishing cervical cancer from healthy subjects.

Epidemiology and risk factors of bloodstream infections among adolescents and young adults with acute lymphoblastic leukaemia: An 11-year retrospective cohort study.

Adolescent and young adults (AYAs) belong to a unique category of patients diagnosed with acute lymphoblastic leukaemia (ALL). Bloodstream infection (BSI) is a leading cause of treatment-related mortality in ALL patients. However, the epidemiology and risk factors for mortality from BSIs in AYA patients remain unclear. In this study, we analysed these aspects in AYAs patients and compared similarities and differences with children (<15 years old) and older adults (>39 years old). We analysed the pathogenic epidemiology, antibiotic resistance and BSI risk factors of 73 children, 180 AYAs, and 110 older adults with ALL in three comprehensive hospitals from January 2010 to August 2021. The data on BSIs in AYAs were compared to that of the other two groups. In this study, the epidemiology of BSIs in AYAs was similar to that of older adult patients. Concerning clinical characteristics, most AYAs and older adults with BSIs were in a relapsed or uncontrolled state (34.5% vs. 35.4%, p = 0.861). In terms of pathogen distribution, Gram-negative bacteria (GNB) were the most common causative pathogens in AYAs and older adult groups. Extended-spectrum beta-lactamase (ESBL)-producing bacteria were more commonly found in AYAs than in children (32.8% vs. 16.4%, p = 0.09). Regarding risk factors, the length of hospitalization (>14 days) and renal inadequacy (creatinine ≥ 177 µmol/L) were influencing factors for 30-day mortality in AYAs patients with BSIs. In our study, AYA patients with BSIs showed clinical characteristics and pathogen distributions similar to those of older adult patients but quite different from those of children.

Raman spectroscopy combined with multivariate statistical algorithms for the simultaneous screening of cervical and breast cancers.

Breast and cervical cancers are becoming the leading causes of death among women worldwide, but current diagnostic methods have many drawbacks, such as being time-consuming and high cost. Raman spectroscopy, as a rapid, reliable, and non-destructive spectroscopic detection technique, has achieved many breakthrough results in the screening and prognosis of various cancer tumors. Therefore, in this study, Raman spectroscopy technology was used to diagnose breast cancer and cervical cancer. A total of 225 spectra were recorded from 87 patients with cervical cancer, 60 patients with breast cancer, and 78 healthy individuals. The obvious difference in Raman spectrum between the three groups was mainly shown at 809 cm-1 (tyrosine), 958 cm-1 (carotenoid), 1004 cm-1 (phenylalanine), 1154 cm-1 (ß-carotene), 1267 cm-1 (Amide III), 1445 cm-1 (phospholipids), 1515 cm-1 (ß-carotene), and 1585 cm-1 (C = C olefinic stretch). We used one-way analysis of variance for these peaks and demonstrated that they were significantly different. Then, we combined the detected Raman spectra with multivariate statistical calculations using the principal component analysis-linear discrimination algorithm (PCA-LDA) to discriminate between the three groups of collected serum samples. The diagnostic results showed that the model's accuracy, precision, recall, and F1 score of the model were 92.90%, 92.62%, 92.10%, and 92.36%, respectively. These results suggest that Raman spectroscopy can achieve ultra-sensitive detection of serum, and the developed diagnostic models have great potential for the prognosis and simultaneous screening of cervical and breast cancers.

Efficacy and Safety in Early application of Ruxolinitib for high-risk: Acute lymphoblastic leukemia to prevent GVHD and recurrence after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been identified as the potentially curative treatment for high-risk acute lymphoblastic leukemia (ALL) in adult patients. However, relapse of the disease and/or development of graft-versus-host disease (GVHD) remain to be the most common barriers for successful allo-HSCT. Preclinical studies showed that ruxolitinib, a Janus tyrosine kinase (Jak)1 and Jak2 inhibitor, has a selective anti-GVHD effects while preserving a potent graft-versus-leukemia (GVL) effect. Our study aimed to investigate the efficacy and safety in early application of ruxolitinib for the high-risk ALL patients to prevent GVHD. METHODS: There were eight patients undergoing allo-HSCT at the Bone Marrow Transplantation Center of the Third Xiangya Hospital of Central South University between April 2020 and April 2021. Ruxolitinib (5-10 mg twice daily) was administered early (median time: 45 days) after stem cell infusion. RESULTS: After a median follow-up of 14 months (range from 8 to 18 months), the ALL disease relapse occurred in two cases. Among all eight patients, two of them developed grade I/II acute (a) GVHD, while no patient developed grade III/IV aGVHD, and one patient developed chronic (c) GVHD. As for the virus activation, no patient developed EBV activation or EBV related lymphoproliferative disease, and three patients developed CMV activation. Our results suggest that the early application of ruxolitinib could safely and effectively prevent the occurrence of GVHD after allo-HSCT for the high-risk ALL patients. However, it may have a limited effect on preventing the recurrence of high-risk ALL and thus may require additional therapy with other anti-relapse drugs. CONCLUSIONS: Our preliminary observations suggest that an early application of ruxolitinib can safely and effectively prevent the occurrence of GVHD after allo-HSCT for the high-risk ALL patients. However, ruxolitinib may have a limited effect on preventing the ALL recurrence of high-risk patients.

BALF metagenomic next-generation sequencing analysis in hematological malignancy patients with suspected pulmonary infection: clinical significance of negative results.

Purpose: Metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) is gradually being used in hematological malignancy (HM) patients with suspected pulmonary infections. However, negative results are common and the clinical value and interpretation of such results in this patient population require further analysis. Methods: Retrospective analysis of 112 HM patients with suspected pulmonary infection who underwent BALF mNGS and conventional microbiological tests. The final diagnosis, imaging findings, laboratory results and treatment regimen of 29 mNGS-negative patients were mainly analyzed. Results: A total of 83 mNGS positive and 29 negative patients (15 true-negatives and 14 false-negatives) were included in the study. Compared to false-negative patients, true-negative patients showed more thickening of interlobular septa on imaging (p < 0.05); fewer true-negative patients had acute respiratory symptoms such as coughing or sputum production (p < 0.05) clinically; On the aspect of etiology, drug-related interstitial pneumonia (6/15, 40%) was the most common type of lung lesion in true-negative patients; on the aspect of pathogenesis, false-negative patients mainly missed atypical pathogens such as fungi and tuberculosis (8/14, 57.1%). Regarding treatment, delayed anti-infection treatment occurred after pathogen missing in mNGS false-negative patients, with the longest median time delay observed for anti-tuberculosis therapy (13 days), followed by antifungal therapy (7 days), and antibacterial therapy (1.5 days); the delay in anti-tuberculosis therapy was significantly longer than that in antibacterial therapy (p < 0.05). Conclusion: For HMs patients with imaging showing thickening of interlobular septa and no obvious acute respiratory symptoms, lung lesions are more likely caused by drug treatment or the underlying disease, so caution should be exercised when performing BALF mNGS. If BALF mNGS is negative but infection is still suspected, atypical pathogenic infections should be considered.

rRNA-Derived Small RNA rsRNA-28S Regulates the Chemoresistance of Prostate Cancer Cells by Targeting PTGIS.

BACKGROUND: rRNA-derived small RNAs (rsRNAs) represent a novel class of small non-coding RNAs (sncRNAs), produced by the specific cleavage of rRNAs; however, their roles in tumor development are unclear. In the present study, we explored the effect of a kind of rsRNA-28S, which originates from 28S rRNA, on the chemoresistance of prostate cancer cells and the mechanisms underlying its effect. METHODS: Quantitative reverse transcription PCR (RT-PCR) was performed to quantify rsRNA-28S levels in serum samples taken from prostate cancer patients. DU-145R cells, which are resistant to both paclitaxel and docetaxel, were generated from parental DU-145 cells. Northern blot was conducted to detect cellular rsRNA-28S levels following drug treatments. To verify the effect of rsRNAs-28S on chemoresistance, antisense oligonucleotides were utilized to block rsRNA-28S functions, and a series of assays were further performed, such as cell viability, cell proliferation, colony formation and tumor sphere formation. The target gene of rsRNA-28S was explored using dual-luciferase reporter gene assay. RESULTS: The rsRNA-28S level was reduced in the serum samples of patients who received chemotherapy compared to that of patients who did not. Furthermore, the rsRNA-28S level was remarkably declined in DU-145R cells, and drug treatments decreased the levels of rsRNA-28S in DU-145 and DU-145R cells. Moreover, rsRNA-28S inhibition enhanced the chemoresistance of prostate cancer cells as well as their cancer stem cell characteristics. Mechanistically, the prostaglandin I2 synthase (PTGIS) gene transcript was verified as a target of rsRNA-28S, as rsRNA-28S inhibited the translation of PTGIS mRNA by directly binding the 3' untranslated region of PTGIS mRNA. rsRNA-28S inhibition was also found to increase PTGIS abundance, and PTGIS overexpression significantly enhanced prostate cancer cell chemoresistance. CONCLUSIONS: Our findings indicate that rsRNA-28S attenuates prostate cancer cell chemoresistance by downregulating its target gene PTGIS. This study not only greatly contributes to systematic identification and functional elucidation of chemoresistance relevant rsRNAs, but also promotes rsRNA-included combinatorial therapeutic regimens for cancer.

Diagnoses in multiple types of cancer based on serum Raman spectroscopy combined with a convolutional neural network: Gastric cancer, colon cancer, rectal cancer, lung cancer.

Cancer is one of the major diseases that seriously threaten human health. Timely screening is beneficial to the cure of cancer. There are some shortcomings in current diagnosis methods, so it is very important to find a low-cost, fast, and nondestructive cancer screening technology. In this study, we demonstrated that serum Raman spectroscopy combined with a convolutional neural network model can be used for the diagnosis of four types of cancer including gastric cancer, colon cancer, rectal cancer, and lung cancer. Raman spectra database containing four types of cancer and healthy controls was established and a one-dimensional convolutional neural network (1D-CNN) was constructed. The classification accuracy of the Raman spectra combined with the 1D-CNN model was 94.5%. A convolutional neural network (CNN) is regarded as a black box, and the learning mechanism of the model is not clear. Therefore, we tried to visualize the CNN features of each convolutional layer in the diagnosis of rectal cancer. Overall, Raman spectroscopy combined with the CNN model is an effective tool that can be used to distinguish different cancer from healthy controls.

Clinical, radiological and pathological characteristics of moderate to fulminant psittacosis pneumonia.

BACKGROUND: Psittacosis pneumonia is a community-acquired pneumonia caused by Chlamydia psittaci. It is usually under-diagnosed due to its atypical clinical presentation and lack of routine laboratory tests. METHODS: To better understand the clinical features, 52 patients diagnosed with psittacosis pneumonia by metagenomic next-generation sequencing (mNGS) were enrolled in this study. The clinical, radiological and pathological characteristics were retrospectively analyzed. RESULTS: The onset of psittacosis pneumonia in this study occurred all year round, with a peak from December to January. Most of the patients were 51-80 years old. About 65.38% of patients had a history of exposure to poultry or parrots. Abnormalities of multiple clinical signals were detected in these patients. Elevated levels of neutrophil ratio, C-reactive protein, erythrocyte sedimentation rate, and procalcitonin were detected in most patients. Radiological evidence revealed air-space consolidation or ground-glass opacities in lungs of all patients, which is the typical feature of psittacosis pneumonia. In addition, hyperemia, swelling of bronchial mucosa, and bronchial patency were detected by bronchoscopy in all patients, and bronchial sub-mucosal edema, inflammatory cells infiltration and alveolar epithelial hyperplasia were identified in the bronchial mucosa and alveolar tissue. Beta-lactam antibiotics were administered for empirical treatment before mNGS in 17 patients but showed no improvement. The treatment was switched to doxycycline or moxifloxacin immediately since psittacosis pneumonia were suspected and confirmed by mNGS detection (within 48 hours). After receiving adjustment of treatment, 94.23% (49/52) of patients were cured successfully. CONCLUSIONS: In conclusion, mNGS may be a promising approach for clinical diagnosis of psittacosis. For patients with a history of exposure to birds, hyperpyrexia, nonproductive cough, multiple elevated inflammatory markers, and air-space consolidation in lung, psittacosis pneumonia should be considered, especially when beta-lactam antibiotics showed limited efficacy.

The Threat of Carbapenem-Resistant Gram-Negative Bacteria in Patients with Hematological Malignancies: Unignorable Respiratory Non-Fermentative Bacteria-Derived Bloodstream Infections.

Background: Carbapenem-resistant Gram-negative bacteria (CRGNB) bloodstream infection (BSI) pose a significant threat to the prognosis of hematologic malignancies (HM) patients. Understanding the distribution of pathogenic bacteria, changes in carbapenem-resistant trends, risk factors for CRGNB infections, and exploring the early detection measures can help reduce mortality. Methods: We conducted a multicenter retrospective study of Gram-negative bacteria (GNB) BSI in patients with HM in three university-affiliated hospitals in Hunan Province, China, from January 2010 to December 2020. Demographic and clinical data were collected from the hospital electronic medical records system. Results: CRGNB caused 138 (15.3%) of 902 GNB BSI. The detection rate of CRGNB increased from 6.4% in 2010-2012 to 35.4% in 2019-2020. The 7-day mortality rate was significantly higher in patients with CRGNB BSI than in patients with carbapenem-susceptible Gram-negative bacteria (CSGNB) BSI [31.9% (44/138) vs 9.7% (74/764), P < 0.001], and the mortality rate in patients with carbapenem-resistant non-fermenting bacteria (CRNFB) bloodstream infections was generally higher than that of carbapenem-resistant Enterobacteriaceae (CRE). Urinary catheter (OR, 2.814; CI=1.395-5.680; P=0.004) and prior exposure to carbapenem (OR, 4.372; CI=2.881-6.635; P<0.001) were independent risk factors for CRGNB BSI. Analysis of co-infections showed that 50%-85% of patients with CRGNB BSI had pulmonary infections, sputum culture results suggested that sputum culture positivity rate was as high as 57.1%-66.7% in patients with carbapenem-resistant Acinetobacter baumannii (CRAB) and Stenotrophomonas maltophilia BSI, and the results of antimicrobial susceptibility testing of sputum cultures were consistent with the blood cultures. Conclusion: Carbapenem resistance has dramatically increased in HM patients with GNB BSI in recent years and is associated with a worse outcome, especially for non-fermenting bacteria. In high-risk patients, early screening of the respiratory tract specimens may help to detect CRNFB colonization and protect patients from breakthrough BSI.

A nomogram to predict in-hospital mortality for post-gastrointestinal resection surgery patients in intensive care units: A retrospective cohort study.

BACKGROUND: The global volume of gastrointestinal surgery has increased steadily. However, there is still a lack of studies focused on the risk factors for post-gastrointestinal resection surgery patients in the intensive care units. METHODS: Post gastrointestinal resection surgery patient data were collected from the Medical Information Mart for Intensive Care (MIMIC-III) database and divided into training set and validation set, then analyzed by Univariate and multiple logistic regression. RESULTS: 795 patients were finally enrolled in our cohort. Multiple logistic regression showed that age (1.029 [1.006-1.053]), temperature (0.337 [0.207-0.547]), respiratory rate (1.133 [1.053-1.218]), mean arterial pressure (1.204 [1.039-1.396]), lactate (1.288 [1.112-1.493]), BUN (1.025 [1.010-1.040]) and vasopressor use (4.777 [2.499-9.130]) were independent factors associated with in-hospital mortality. Our new predicted nomogram achieved a better accuracy than SOFA score, SAPS-Ⅱ score, APACHE-Ⅲ score, and Elixhauser score. CONCLUSION: Our nomogram model could well predict in-hospital mortality for post-GI resection surgery patients receiving intensive care.

A nanodrug system overexpressed circRNA_0001805 alleviates nonalcoholic fatty liver disease via miR-106a-5p/miR-320a and ABCA1/CPT1 axis.

Our study aimed to explore the function of circRNA_0001805 in the pathogenesis of NAFLD and the underlying mechanism. A nanodrug system (GA-RM/GZ/PL) was constructed to overexpress circRNA_0001805 specifically in hepatocytes for the treatment of NAFLD. Fat droplet accumulation in cultured cells and mouse hepatic tissues was detected using Oil Red O or H&E staining. The relative expression of circRNAs, genes associated with lipogenesis was quantified by qRT-PCR. Interactions between circRNA_0001805 and miR-106a-5p/miR-320a, between miR-106a-5p/miR-320a and ABCA1/CPT1 were confirmed by dual-luciferase reporter assay. A novel metalorganic framework nanocarrier (GZ) was prepared from glycyrrhizic acid and zinc ions (Zn2+), and this nanocarrier was loaded with the circRNA_0001805 plasmid to construct a nanocore (GZ/PL). Then, this GZ/PL was coated with a galactose-modified RBC membrane (GA-RM) to generate GA-RM/GZ/PL. CircRNA_0001805 expression was downregulated in FFA-challenged primary hepatocytes, HFD-fed mice and NAFLD patients. Overexpressed circRNA_0001805 attenuated NAFLD development by suppressing lipid metabolism disorder and inflammation. CircRNA_0001805 targeted miR-106a-5p/miR-320a, which served as an upstream inhibitor of ABCA1/CPT1 and collaboratively regulated NAFLD progression. GA-RM/GZ/PL targeted hepatocytes, overexpressed circRNA_0001805, released glycyrrhizic acid to reduce the accumulation of lipids in the liver and played a synergistic role against NAFLD-induced lipid metabolism disorder.

Abnormal m6A modification in non-alcoholic fatty liver disease. / éžé ’ç²¾æ€§è„‚è‚ªæ€§è‚ç— çš„å¼‚å¸¸m6A修饰.

OBJECTIVES: Non-alcoholic fatty liver disease has seriously affected people's health. Recent studies have found that N6-methyladenosine (m6A) methylation is involved in the lipid metabolism process of the body, but the study on the level of m6A modification in NAFLD is still not available. This study aims to explore the changes in the level of RNA m6A methylation modification in NAFLD liver tissues, and to provide experimental and theoretical basis for in-depth study on the role of RNA m6A methylation in the occurrence and development of NAFLD. METHODS: Changes in the m6A level in NAFLD liver tissues were measured by liquid chromatography-mass spectrometry (LC-MS). Total RNA was extracted from liver tissues of NAFLD patients or normal control individuals and subjected to methylated RNA immunoprecipitation (MeRIP) with microarray analysis (including 44 122 mRNAs and 12 496 lncRNAs) to determine the changes in m6A modification levels across the entire transcriptome. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to annotate the differentially modified mRNAs. Finally, 4 mRNAs and 4 lncRNAs were randomly selected to verify the microarray results by MeRIP and real-time transcription polymerase chain reaction. RESULTS: A total of 176 mRNAs and 44 lncRNAs were found to be differentially m6A-modified in the NAFLD group compared with the control group. Among them, 15 mRNAs and 7 lncRNAs were hypermethylated in NAFLD, while 161 mRNAs and 37 lncRNAs were hypomethylated in NAFLD. GO and pathway analysis showed that the differentially modified mRNAs were enriched mainly in biological processes such as carboxylic acid metabolism and transcriptional regulation. CONCLUSIONS: The m6A modification profile is changed in NAFLD liver tissues compared with normal liver tissues, which may functionally impact the pathophysiological progress in NAFLD.

Gram-Negative Bacteria Bloodstream Infections in Patients with Hematological Malignancies - The Impact of Pathogen Type and Patterns of Antibiotic Resistance: A Retrospective Cohort Study.

BACKGROUND: Enterobacteriaceae (EB) and non-fermentative bacteria (NFB) are the main pathogens responsible for gram-negative bloodstream infections (GN-BSI) in patients with hematological malignancies (HMs). These two pathogen types have heterogeneous resistance mechanisms to antibiotics. However, the impact of pathogen species and pattern of antibiotic resistance on the outcomes of patients with HMs remains unclear. METHODS: We retrospectively collected clinical data of patients with HMs at three comprehensive hospitals in Hunan Province, China, between January 2010 and May 2018. The data analyzed the impact that different species and patterns of antibiotic resistance had on the outcome of patients with HMs. RESULTS: The majority of the 835 monomicrobial isolates collected from patients with HMs and GN-BSIs were Enterobacteriaceae (75.7%). While detections of MDR pathogens in BSIs as a whole are decreasing, sub-analysis shows that detections of extended spectrum ß-lactamase-producing (ESBL) Enterobacteriaceae and carbapenem-resistant pathogens in BISs are rising. Comparing different species, the early mortality rate associated with infections caused by NFB was significantly higher than infections caused by Enterobacteriaceae (22.6% vs 9.7%, p < 0.001). Across different multidrug-resistant (MDR) patterns, ESBL bacteria did not have a significant impact on health outcomes. Carbapenem-resistant bacteria, on the other hand, were observed to significantly affect early mortality rate, such as carbapenem-resistant Klebsiella pneumoniae (36.0% vs 7.6%, P < 0.001) and carbapenem-resistant non-fermentative bacteria (44.7% vs 16.5%, P < 0.001). CONCLUSION: Our findings suggest that both species and patterns of antibiotic resistance can affect the early mortality of patients with HMs during BSI.

The diagnostic potential of gut microbiome for early hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND AND AIMS: Gut microbiota is related with hepatocellular carcinoma (HCC). However, the relationship between the gut microbiota and the hepatitis B virus (HBV)-related HCC remains unclear. We aimed to characterize gut microbiome in HBV-related HCC patients and estimate the clinical potential of gut microbiome as biomarkers for HBV-related HCC. METHODS: We collected fecal and plasma samples from 20 health controls, 20 HBV-related cirrhosis and 20 HBV-related HCC in the First Affiliated Hospital of Chongqing Medical University. The fecal samples were subjected to the V3-V4 region of 16S rRNA Miseq sequencing. Plasma samples were calculated for interleukin-6 (IL-6), IL-2, IL-8, IL-10, tumor necrosis factor α (TNF-α), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Then, we analyzed the correlation between the index and the gut microbiota. RESULTS: We have found that the bacterial richness of the liver cirrhosis group was lower than the HCC group. The bacterial diversities were in consistent with IL-2. The pro-inflammatory bacteria (Veillonella, Escherichia-shigella) have increased in the liver cirrhosis group. The random forest model has achieved an area under the curve value was 94% with 95% CI, 88-100% between the HCC group and the non-HCC group. The results revealed that IL-2 was highly associated with the whole gut bacterial communities of HCC and liver cirrhosis groups. ALT, AST and glutamyl transpeptidase have strongly elevated in liver cirrhosis and HCC groups, which were associated with gut microbiome. CONCLUSIONS: It could be helpful to define the potential bacteria linking to pathological mechanisms of HBV-related HCC. The diagnosis potential of gut microbiome for early HBV-related HCC has been estimated.

Epidemiology, Risk Factors, and Clinical Outcomes of Bloodstream Infection due to Extended-Spectrum Beta-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae in Hematologic Malignancy: A Retrospective Study from Central South China.

Objective: To determine the epidemiology, risk factors, and prognosis of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae bloodstream infections (BSIs) among hematology malignancy (HM) patients in China. Method: From January 2010 to June 2018, we retrospectively collected and analyzed the 449 HM patients with E. coli or K. pneumoniae BSIs from three leading hospitals in Hunan Province, China. Results: Two hundred four (45.4%) patients harbored ESBL-producing bacteremia. The proportion of ESBL-producing bacteremia increased significantly with the growth of the year, with a ratio of 34.47% in 2010-2014 to 54.7% in 2015-2018. Comparing with non-ESBL groups in HM patients, central venous catheter (odds ratio [OR] 1.717, p = 0.009), previous antibiotic exposure (OR 1.559, p = 0.035), and E. coli (OR 2.561, p ≤ 0.001) among ESBL groups were independent risk factors. No significant differences in 30-day mortality were tested in patients with BSI caused by ESBL-producing or non-ESBL-producing E. coli and K. pneumoniae (17.1% vs. 16.7%; p = 0. 893). The proportion of carbapenem used within 72 hours after the onset of bacteremia in two groups was high, which was routinely used as "last-resort drugs" in Gram-negative bacterial infections. Risk factors associated with 30-day mortality in HM patients with E. coli or K. pneumoniae bacteremia were myelodysplastic syndrome, incomplete remission of the disease, Multinational Association of Supportive Care in Cancer score <21, Pitt bacteremia score ≥4, Charlson comorbidity score >3, catheter insertion, use of vasopressors, and inappropriate antibiotics within 72 hours of BSI onset. Conclusions: The results of this study may provide some references for the whole process management of HM patients with BSIs.

Antibiotic susceptibility and prognostic analysis of Gram negative bacterial bloodstream infection in patients with acute leukemia. / æ€¥æ€§ç™½è¡€ç— æ‚£è€ é©å °æ°é˜´æ€§èŒè¡€æµæ„ŸæŸ“çš„è¯æ•åˆ†æžåŠé¢„åŽ.

OBJECTIVES: To analyze the pathogenic distribution, antibiotic susceptibility and prognostic factors for acute leukemia (AL) patients with Gram negative (G-) bacterial bloodstream infection (BSI), in order to provide theoretical basis for reducing the infection-related mortality of AL patients. METHODS: The clinical data of 1 055 AL patients with BSI admitted to the hematology ward of three large-scale hospitals in Hunan Province from January 2010 to December 2018 were collected. The etiology, antibiotic susceptibility data and clinical features of patients with G- bacterial infection were analyzed. RESULTS: G- bacterial infection accounted for 622 AL patients with BSI, and the main pathogens were Escherichia coli (277 strains, 44.53%), Klebsiella pneumoniae (138 strains, 22.19%), and Pseudomonas aeruginosa (81 strains, 13.02%). Most G- bacteria were highly sensitive to carbapenems and ß-lactam/ß-lactamase inhibitor. State of disease, Pitt score ≥4, treatment with vasoactive agents and sensitive antibiotic >48 h were independent risk factors of 30-day mortality. CONCLUSIONS: Rational antibacterial treatment of G- bacterial BSI in AL patients requires adequate acquaintance of the local pathogenic epidemiology and antibiotic susceptibility-monitored data. Broad-spectrum antibiotics covering the most common and more virulent pathogens should be timely applicated and adjusted according to antibiotic susceptibility results and efficacy.

Risk Prediction and Prognosis of Invasive Fungal Disease in Hematological Malignancies Patients Complicated with Bloodstream Infections.

PURPOSE: In patients with hematologic malignancies (HM), bloodstream infections (BSI) and invasive fungal disease (IFD) remain important complications causing considerable mortality and morbidity. At present, the morbidity of IFD and the strategies to initiate antifungal treatment in HM patients with BSI remain unclear. PATIENTS AND METHODS: Patient characteristics, infection-related variables, and therapy-related features of 1374 HM patients with proven BSI from three hospitals were reviewed to investigate the epidemiology, risk factors and prognosis of IFD. RESULTS: The morbidity of proven and probable IFD in HM patients with BSI was 11.2%, and the mortality of those patients was 40.5%. Existing IFD risk scores were not accurate enough in distinguishing these patients benefiting from antifungal prophylaxis. Multivariate logistic regression identified age >45 years, profound neutropenia, hypoproteinemia, and use of vasopressors as independent variables associated with IFD morbidity in HM patients with BSI. In patients with proven and probable IFD patients, age >45 years, Pitt bacteremia score >3, use of vasopressors, abnormal blood coagulation, and initiation of antifungal therapy within 72 hrs after the onset of fever were independent prognostic factors. The mortality was significantly reduced in patients with high-risk factors of IFD if they initiate antifungal treatment within 72 hrs after the onset of fever compared to the patients not. CONCLUSION: The morbidity and mortality of IFD increase significantly in HM patients with BSI. Early antifungal therapy may improve prognosis in HM patients with BSI complicated with IFD risk factors.

Inappropriate initial antimicrobial therapy for hematological malignancies patients with Gram-negative bloodstream infections.

BACKGROUND: Inappropriate initial antimicrobial therapy (IIAT) may increase the mortality rate of hematological malignancies (HMs) patients with Gram-negative bacteria bloodstream infections (GN-BSI). The aim of this study is to determine whether IIAT affects the prognosis in this patient population and recommend the appropriate antibiotic regimen to minimize IIAT. METHODS: We reviewed a retrospective cohort study of 361 HM patients with neutropenic fever from GN-BSI. The patients' clinical characteristics and the results of the drug sensitivity test in vitro were analyzed. RESULTS: IIAT rate was 21.3% in HM patients with neutropenic fever caused by GN-BSI. There was a significant difference in 7-day mortality rate between patients treated with appropriate antibiotics and those with IIAT (7.7% vs 29.9%, p < 0.01). Multivariate analysis confirmed that IIAT was an independent risk factors for early mortality [4.860 (1.541-15.323)]. Drug sensitivity data of GN-bacteria suggested that carbapenems monotherapy or beta-lactamase inhibitors (BLBLI) combined with amikacin as the initial therapy can effectively reduce the IIAT rate. In the stratified antibiogram based on prior antimicrobial exposure, our results showed that BLBLI monotherapy could be initially used as an empirical treatment in patients without prior antimicrobial exposure. In those who had received prior antimicrobial exposure, BLBLI (especially piperacillin-tazobactam) combined with amikacin is recommended. CONCLUSIONS: IIAT was a critical factor contributing to the mortality of HM patients with neutropenic fever from GN-BSI.

ADAR1 may be involved in the proliferation of acute myeloid leukemia cells via regulation of the Wnt pathway.

PURPOSE: Acute myeloid leukemia (AML) is the most common type of leukemia and characterized by the malignant growth of leukemic cells. Adenosine deaminases acting on RNA 1 (ADAR1) have been shown to participate in the proliferation of cancer cells and progression of various cancers. However, the role of ADAR1 in AML has not been investigated. PATIENTS AND METHODS: We compared the expression levels of ADAR1 between samples obtained from different AML patients and controls using quantitative-polymerase chain reaction and Western blotting. We also investigated the functional role and possible mechanisms via silencing the expression of ADAR1 in vitro and in vivo. RESULTS: We found that the mRNA and protein levels of ADAR1 were significantly higher in AML patients. The mRNA expression of ADAR1 was positively correlated with the ratio of leukemic cells. Additionally, silencing of ADAR1 expression significantly suppressed the proliferation of AML cells and induced G0/1 arrest. For the analysis of the mechanism, the quantitative-polymerase chain reaction and Western blotting results revealed that ADAR1 knockdown resulted in the decreased expression of Wingless-Int (Wnt) effectors including ß-catenin, c-Myc, transcription factor 4, and cyclin D2. In the nude mouse model, inhibition of ADAR1 expression reduced the tumorigenic potential and decreased the expression o]f Wnt effectors. CONCLUSION: These results demonstrate that ADAR1 may be involved in the regulation of the proliferation of AML cells partially via regulation of the Wnt signaling pathway.