Characterization of Staphylococcus aureus isolated from patients with burns in a regional burn center, Southeastern China.

BACKGROUND: S.aureus is a predominant pathogen that causes infection in critically ill patients, but little information exists regarding the characterization of S. aureus from different sources in burn patients in southeastern China. METHODS: We enrolled 125 patients with S. aureus infection in burns center between Jan 2014 and Dec 2015. S. aureus isolates were characterized by antimicrobial susceptibility test, toxin gene detection, and molecular typing with multilocus sequence type, staphylococcal protein A (spa) type, and staphylococcal cassette chromosome mec (SCCmec) type. RESULTS: Sixty-eight MRSA were isolated from SSTI and 31 from non-SSTI patients, respectively. Overall, the drug-resistant ability of S. aureus isolated from SSTI was higher than that from non-SSTI groups. SCCmecIII-CC239-t030 was the most common clone (38 from SSTIs, and 8 from non-SSTIs). Seg was the most common enterotoxin gene (21 from SSTIs and 33 from non-SSTIs). Isolates from SSTIs was more likely to carry seb (P = 0.04), while those from non-SSTIs tended to carry sea and seg (P = 0.002 and 0.01, respectively). Although isolates carried four hemolysin genes, there was no significant difference between them (P > 0.05). CONCLUSION: SCCmecIII-CC239-t030 was the most common clone in Jiangxi burns center, China. The molecular characterization of S. aureus was quite different between SSTI and non-SSTI groups.

Drug-resistance dynamics of Staphylococcus aureus between 2008 and 2014 at a tertiary teaching hospital, Jiangxi Province, China.

BACKGROUND: To understand the relationship between the Staphylococcus aureus infection rate and the reasonable usage of antibiotics, which will help in the effective control of MRSA infection. METHODS: All data were obtained by the application of the nosocomial infection surveillance network. Drug resistance, departmental sources, and isolated sites as well as infection rate variations of S. aureus were analyzed in the 7-year period in key departments. RESULTS: Between 2008 and 2014, 2525 strains of S. aureus isolates, mainly from sputum, skin/soft tissue, bloodstreams were collected from several hospital departments including respiratory, burn, brain surgery, orthopedics, ICU, and emergency. During these periods, the resistance rate of S. aureus to most drugs, including oxacillin, tetracycline, erythromycin, clindamycin, gentamicin, and ciprofloxacin, showed a tendency to decrease. The resistance to sulphamethoxazole/trimethoprim showed the opposite trend (P = 0.075) and there were no S. aureus strains resistant to linezolid and vancomycin. The MRSA infection rate was different across crucial hospital departments, with the burns department and ICU maintaining a high infection level. Over the 7-year period, both the brain surgery and the emergency departments had an expected upward trend (P < 0.05), while the orthopedic department showed a clear downward trend (P < 0.05) in MRSA infection rate. CONCLUSION: Hospitals should continue to maintain the current pattern of antibiotic administration, while more effective measures should be taken to reduce the high MRSA infection rate in some important hospital departments.

Association between green tea intake and risk of gastric cancer: a systematic review and dose-response meta-analysis of observational studies.

OBJECTIVE: To examine and quantify the potential dose-response relationship between green tea intake and the risk of gastric cancer. DESIGN: We searched PubMed, EMBASE, Web of Science, CBM, CNKI and VIP up to December 2015 without language restrictions. SETTING: A systematic review and dose-response meta-analysis of observational studies. SUBJECTS: Five cohort studies and eight case-control studies. RESULTS: Compared with the lowest level of green tea intake, the pooled relative risk (95 % CI) of gastric cancer was 1·05 (0·90, 1·21, I 2=20·3 %) for the cohort studies and the pooled OR (95 % CI) was 0·84 (0·74, 0·95, I 2=48·3 %) for the case-control studies. The pooled relative risk of gastric cancer was 0·79 (0·63, 0·97, I 2=63·8 %) for intake of 6 cups green tea/d, 0·59 (0·42, 0·82, I 2=1·0 %) for 25 years of green tea intake and 7·60 (1·67, 34·60, I 2=86·5 %) for drinking very hot green tea. CONCLUSIONS: Drinking green tea has a certain preventive effect on reducing the risk of gastric cancer, particularly for long-term and high-dose consumption. Drinking too high-temperature green tea may increase the risk of gastric cancer, but it is still unclear whether high-temperature green tea is a risk factor for gastric cancer. Further studies should be performed to obtain more detailed results, including other gastric cancer risk factors such as smoking and alcohol consumption and the dose of the effective components in green tea, to provide more reliable evidence-based medical references for the relationship between green tea and gastric cancer.

Identification and validation of ferroptosis-related genes for diabetic retinopathy.

Diabetic retinopathy (DR) is a leading cause of blindness, and ferroptosis may be an essential component of the pathological process of DR. In this study, we aimed to screen five hub genes (TLR4, CAV1, HMOX1, TP53, and IL-1B) using bioinformatics analysis and experimentally verify their expression and effects on ferroptosis and cell function. The online Gene Expression Omnibus microarray expression profiling datasets GSE60436 and GSE1025485 were selected for investigation. Ferroptosis-related genes that might be differentially expressed in DR were identified. Then, Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein-protein interaction (PPI) network analyses were conducted to characterize the differentially-expressed ferroptosis-related genes. After tissue-specific analyses and external dataset validation of hub genes, the mRNA and protein levels of hub genes in retinal microvascular endothelial cells (HRMECs) symbiotic with high glucose were verified using real-time quantitative PCR (qRT-PCR) and immunocytochemistry (ICC). Finally, hub genes were knocked down using siRNA, and changes in ferroptosis and cell function were observed. Based on the differential expression analysis, 19 ferroptosis-related genes were identified. GO and KEGG enrichment analyses showed that ferroptosis-related genes were significantly enriched in reactive oxygen species metabolic processes, necrotic cell death, hypoxia responses, iron ion responses, positive regulation of cell migration involved in sprouting angiogenesis, NF-kappa B signaling pathway, ferroptosis, fluid shear stress, and atherosclerosis. Subsequently, PPI network analysis and critical module construction were used to identify five hub genes. Based on bioinformatics analysis of mRNA microarrays, qRT-PCR confirmed higher mRNA expression of five genes in the DR model, and immunocytochemistry confirmed their higher protein expression. Finally, siRNA interference was used to verify the effects of five genes on ferroptosis and cell function. Based on bioinformatics analysis, five potential genes related to ferroptosis were identified, and their upregulation may affect the onset or progression of DR. This study sheds new light on the pathogenesis of DR.

The factors that influence the diagnostic accuracy and sample adequacy of EUS-guided tissue acquisition for the diagnosis of solid pancreatic lesions.

Background and Objectives: EUS-guided tissue acquisition (EUS-TA) is the preferred method to acquire pancreatic cancer (PC) tissues. The factors associated with false-negative outcomes and inadequate samples should be explored to gain an understanding of EUS-TA. Methods: The patients who underwent EUS-TA for suspected solid PC but whose results were false-negative were analyzed. The PC patients who underwent EUS-TA with true-positive results on the first day of every month during the study period were selected as the control group. The factors influencing diagnostic accuracy and sample adequacy were explored. Results: From November 2017 to January 2022, 184 patients were included in the false-negative group, and 175 patients were included in the control group. Multivariate logistic regression demonstrated that the recent acute pancreatitis [odds ratio (OR): 0.478, 95% confidence interval (CI): 0.250-0.914, P = 0.026] and high echo component within the tumor (OR: 0.103, 95% CI: 0.027-0.400, P = 0.001) were independently associated with false-negative EUS-TA results. Meanwhile, using fine-needle biopsy (FNB) needles (OR: 2.270, 95% CI: 1.277-4.035, P = 0.005), more needle passes (OR: 1.651,95% CI: 1.239-2.199, P = 0.005), large tumor size (OR: 1.053, 95% CI: 1.029-1.077, P < 0.001), and high CA-19-9 level (OR: 1.001, 95% CI: 1.000-1.001, P = 0.019) were independently associated with true-positive EUS-TA outcomes. Three needle passes are needed to achieve optimal EUS-TA outcomes. Tumor location in the body/tail (OR: 1.38, 95% CI: 1.01-1.72; P = 0.04), needle passes ≥3 (OR: 1.90; 95% CI: 1.22-2.56; P < 0.001), and using the FNB needle (OR: 2.10; 95%: 1.48-2.85; P < 0.001) were independently related to sample adequacy. Conclusion: Numerous factors were identified to be associated with the diagnostic accuracy and sample adequacy of EUS-TA.

Combination of Anti-thymocyte Globulin with Post-transplant Cyclophosphamide for GVHD Prophylaxis in Patients Undergoing Haploidentical Hematopoietic Stem Cell Transplantation: Systematic Review and Meta-analysis.

A new strategy combining anti-thymocyte globulin with post-transplant cyclophosphamide (ATG/PTCy) for graft-versus-host disease (GVHD) prevention was developed. This study aims to perform a systematic review and meta-analysis of studies comparing ATG/PTCy with ATG or PTCy in patients with hematological malignancies undergoing haploidentical hematopoietic stem cell transplantation. Meta-analysis was conducted with Review Manager version 5.4; pooled risk ratios (RRs) and hazard ratios (HRs) were calculated for dichotomous data and time-to-event data, respectively. A fixed-effects model was used if there was no significant heterogeneity. Literature search and study selection identified 14 eligible studies, including both randomized controlled trial and retrospective comparative studies. Different dosage adjustment strategies were applied; the total dose was 2.5-10 mg/kg for ATG and 29-100 mg/kg for PTCy. Meta-analysis results suggest that ATG/PTCy is associated with significantly lower risk of grades II-IV acute GVHD compared with ATG (RR 0.52; 95% CI: 0.41-0.65; P < .00001) and PTCy (RR 0.53; 95% CI: 0.34-0.83; P = .005) without increasing risk of disease relapse. In addition, ATG/PTCy is associated with significantly better overall survival and GVHD-free/relapse-free survival than ATG and PTCy. Future research is required to further establish the benefits of ATG/PTCy and determine the optimal dosage adjustment strategies. BACKGROUND: Haploidentical stem cell transplantation (haplo-HSCT) is associated with higher incidences of graft-versus-host disease (GVHD). A new strategy combining anti-thymocyte globulin with post-transplant cyclophosphamide (ATG/PTCy) for GVHD prevention has been developed, but its benefits and risks remain unclear. OBJECTIVE: This study aims to performs a systematic review and meta-analysis of studies comparing ATG/PTCy with ATG or PTCy in patients with hematological malignancies undergoing haplo-HSCT. STUDY DESIGN: Literature search was performed in databases including Ovid Medline, Embase, Cochrane Library and China Biology Medicine (CBM). Two investigators independently screened eligible studies and extracted data. Meta-analysis was conducted with Review Manager version 5.4; pooled hazard ratios (HRs) for time-to-event outcomes were obtained using a generic inverse-variance method, and pooled risk ratios (RRs) for dichotomous data were obtained using the Mantel-Haenszel method. A fixed-effects model was adopted if there was no significant heterogeneity. The primary outcome is incidence of acute GVHD. RESULTS: Literature search and study selection identified 14 eligible studies, including both 1 randomized controlled trial and 13 retrospective comparative studies. Different dosage adjustment strategies were applied; the total dose was 2.5-10 mg/kg for ATG and 29-100 mg/kg for PTCy. Meta-analysis results suggest that ATG/PTCy is associated with significantly lower risk of grades II-IV acute GVHD compared with ATG (RR 0.52; 95% CI: 0.41-0.65; P < .00001) and PTCy (RR 0.53; 95% CI: 0.34-0.83; P = .005) without increasing risk of disease relapse. In addition, ATG/PTCy is associated with significantly lower risk of grades III-IV acute GVHD (RR 0.33; 95% CI: 0.23-0.49; P < .00001) and chronic GVHD (RR 0.65; 95% CI: 0.51-0.81; P = .0002) in comparison with ATG. Further analyses suggest that ATG/PTCy is associated with significantly better overall survival and GVHD-free/relapse-free survival than ATG and PTCy, but the risks of cytomegalovirus (RR 1.42; 95% CI: 1.03-1.95; P = .03) and Epstein Barr Virus (RR 3.17; 95% CI: 1.61-6.23; P = .0008) reactivation are higher when compared with PTCy. CONCLUSIONS: Our results suggest that the combination of ATG with PTCy for GVHD prevention in haplo-HSCT is associated with improved efficacy but higher risk of infection. Future research is required to further establish the benefits and risks of ATG/PTCy and determine the optimal dosage adjustment strategies.

Myeloablative conditioning regimens in adult patients with acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplantation in complete remission: a systematic review and network meta-analysis.

The optimal myeloablative conditioning (MAC) regimens in adult patients with acute myeloid leukemia (AML) undergoing allogeneic hemopoietic stem cell transplantation (allo-HSCT) in complete remission (CR) remain unclear. We performed a systematic review and network meta-analysis to compare the effects of different MAC regimens. Bayesian network meta-analysis was performed using WinBUGS version 1.4.3. The commonly used MAC regimen Bu/Cy (4-day busulfan for toal 16 mg/kg orally or 12.8 mg/kg intravenously, plus 2-day cyclophosphamide for toal 120 mg/kg intravenously) is chosen as the common comparator. Pooled hazard ratios (HRs) with the associated 95% credibility interval (95% CrI) are obtained for all comparisons. We included 19 eligible studies, involving 8104 AML patients and 9 MAC regimens. Compared with Bu/Cy, 3-day busulfan plus fludarabine and thiotepa (Bu3/Flu/TT) is associated with significantly better overall survival (HR, 0.70; 95% CrI, 0.51 to 0.96) and lower risk of relapse (HR, 0.59; 95% CrI, 0.35 to 0.98). Bu3/Flu/TT is also associated with superior overall survival than Cy/TBI (cyclophosphamide plus total body irradiation), and lower risk of relapse than Bu4/Flu (4-day busulfan plus fludarabine). These results suggest that thiotepa-based new MAC regimen Bu3/Flu/TT is associated with improved outcomes in AML patients undergoing allo-HSCT in CR and worth further investigation.

Corrigendum: Potential gut microbiota features for non-invasive detection of schistosomiasis.

[This corrects the article DOI: 10.3389/fimmu.2022.941530.].

Potential Gut Microbiota Features for Non-Invasive Detection of Schistosomiasis.

The gut microbiota has been identified as a predictive biomarker for various diseases. However, few studies focused on the diagnostic accuracy of gut microbiota derived-signature for predicting hepatic injuries in schistosomiasis. Here, we characterized the gut microbiomes from 94 human and mouse stool samples using 16S rRNA gene sequencing. The diversity and composition of gut microbiomes in Schistosoma japonicum infection-induced disease changed significantly. Gut microbes, such as Bacteroides, Blautia, Enterococcus, Alloprevotella, Parabacteroides and Mucispirillum, showed a significant correlation with the level of hepatic granuloma, fibrosis, hydroxyproline, ALT or AST in S. japonicum infection-induced disease. We identified a range of gut bacterial features to distinguish schistosomiasis from hepatic injuries using the random forest classifier model, LEfSe and STAMP analysis. Significant features Bacteroides, Blautia, and Enterococcus and their combinations have a robust predictive accuracy (AUC: from 0.8182 to 0.9639) for detecting liver injuries induced by S. japonicum infection in humans and mice. Our study revealed associations between gut microbiota features and physiopathology and serological shifts of schistosomiasis and provided preliminary evidence for novel gut microbiota-derived features for the non-invasive detection of schistosomiasis.

COVID-19 epidemic and public health interventions in Shanghai, China: Statistical analysis of transmission, correlation and conversion.

Background: The Shanghai COVID-19 epidemic is an important example of a local outbreak and of the implementation of normalized prevention and disease control strategies. The precise impact of public health interventions on epidemic prevention and control is unknown. Methods: We collected information on COVID-19 patients reported in Shanghai, China, from January 30 to May 31, 2022. These newly added cases were classified as local confirmed cases, local asymptomatic infections, imported confirmed cases and imported asymptomatic infections. We used polynomial fitting correlation analysis and illustrated the time lag plot in the correlation analysis of local and imported cases. Analyzing the conversion of asymptomatic infections to confirmed cases, we proposed a new measure of the conversion rate (C r ). In the evolution of epidemic transmission and the analysis of intervention effects, we calculated the effective reproduction number (R t ). Additionally, we used simulated predictions of public health interventions in transmission, correlation, and conversion analyses. Results: (1) The overall level of R t in the first three stages was higher than the epidemic threshold. After the implementation of public health intervention measures in the third stage, R t decreased rapidly, and the overall R t level in the last three stages was lower than the epidemic threshold. The longer the public health interventions were delayed, the more cases that were expected and the later the epidemic was expected to end. (2) In the correlation analysis, the outbreak in Shanghai was characterized by double peaks. (3) In the conversion analysis, when the incubation period was short (3 or 7 days), the conversion rate fluctuated smoothly and did not reflect the effect of the intervention. When the incubation period was extended (10 and 14 days), the conversion rate fluctuated in each period, being higher in the first five stages and lower in the sixth stage. Conclusion: Effective public health interventions helped slow the spread of COVID-19 in Shanghai, shorten the outbreak duration, and protect the healthcare system from stress. Our research can serve as a positive guideline for addressing infectious disease prevention and control in China and other countries and regions.

Integrating Internet multisource big data to predict the occurrence and development of COVID-19 cryptic transmission.

With the recent prevalence of COVID-19, cryptic transmission is worthy of attention and research. Early perception of the occurrence and development risk of cryptic transmission is an important part of controlling the spread of COVID-19. Previous relevant studies have limited data sources, and no effective analysis has been carried out on the occurrence and development of cryptic transmission. Hence, we collect Internet multisource big data (including retrieval, migration, and media data) and propose comprehensive and relative application strategies to eliminate the impact of national and media data. We use statistical classification and regression to construct an early warning model for occurrence and development. Under the guidance of the improved coronavirus herd immunity optimizer (ICHIO), we construct a "sampling-feature-hyperparameter-weight" synchronous optimization strategy. In occurrence warning, we propose an undersampling synchronous evolutionary ensemble (USEE); in development warning, we propose a bootstrap-sampling synchronous evolutionary ensemble (BSEE). Regarding the internal training data (Heilongjiang Province), the ROC-AUC of USEE3 incorporating multisource data is 0.9553, the PR-AUC is 0.8327, and the R2 of BSEE2 fused by the "nonlinear + linear" method is 0.8698. Regarding the external validation data (Shaanxi Province), the ROC-AUC and PR-AUC values of USEE3 were 0.9680 and 0.9548, respectively, and the R2 of BSEE2 was 0.8255. Our method has good accuracy and generalization and can be flexibly used in the prediction of cryptic transmission in various regions. We propose strategy research that integrates multiple early warning tasks based on multisource Internet big data and combines multiple ensemble models. It is an extension of the research in the field of traditional infectious disease monitoring and has important practical significance and innovative theoretical value.

Using machine learning models to predict the duration of the recovery of COVID-19 patients hospitalized in Fangcang shelter hospital during the Omicron BA. 2.2 pandemic.

Background: Factors that may influence the recovery of patients with confirmed SARS-CoV-2 infection hospitalized in the Fangcang shelter were explored, and machine learning models were constructed to predict the duration of recovery during the Omicron BA. 2.2 pandemic. Methods: A retrospective study was conducted at Hongqiao National Exhibition and Convention Center Fangcang shelter (Shanghai, China) from April 9, 2022 to April 25, 2022. The demographics, clinical data, inoculation history, and recovery information of the 13,162 enrolled participants were collected. A multivariable logistic regression model was used to identify independent factors associated with 7-day recovery and 14-day recovery. Machine learning algorithms (DT, SVM, RF, DT/AdaBoost, AdaBoost, SMOTEENN/DT, SMOTEENN/SVM, SMOTEENN/RF, SMOTEENN+DT/AdaBoost, and SMOTEENN/AdaBoost) were used to build models for predicting 7-day and 14-day recovery. Results: Of the 13,162 patients in the study, the median duration of recovery was 8 days (interquartile range IQR, 6-10 d), 41.31% recovered within 7 days, and 94.83% recovered within 14 days. Univariate analysis showed that the administrative region, age, cough medicine, comorbidities, diabetes, coronary artery disease (CAD), hypertension, number of comorbidities, CT value of the ORF gene, CT value of the N gene, ratio of ORF/IC, and ratio of N/IC were associated with a duration of recovery within 7 days. Age, gender, vaccination dose, cough medicine, comorbidities, diabetes, CAD, hypertension, number of comorbidities, CT value of the ORF gene, CT value of the N gene, ratio of ORF/IC, and ratio of N/IC were related to a duration of recovery within 14 days. In the multivariable analysis, the receipt of two doses of the vaccination vs. unvaccinated (OR = 1.118, 95% CI = 1.003-1.248; p = 0.045), receipt of three doses of the vaccination vs. unvaccinated (OR = 1.114, 95% CI = 1.004-1.236; p = 0.043), diabetes (OR = 0.383, 95% CI = 0.194-0.749; p = 0.005), CAD (OR = 0.107, 95% CI = 0.016-0.421; p = 0.005), hypertension (OR = 0.371, 95% CI = 0.202-0.674; p = 0.001), and ratio of N/IC (OR = 3.686, 95% CI = 2.939-4.629; p < 0.001) were significantly and independently associated with a duration of recovery within 7 days. Gender (OR = 0.736, 95% CI = 0.63-0.861; p < 0.001), age (30-70) (OR = 0.738, 95% CI = 0.594-0.911; p < 0.001), age (>70) (OR = 0.38, 95% CI = 0292-0.494; p < 0.001), receipt of three doses of the vaccination vs. unvaccinated (OR = 1.391, 95% CI = 1.12-1.719; p = 0.0033), cough medicine (OR = 1.509, 95% CI = 1.075-2.19; p = 0.023), and symptoms (OR = 1.619, 95% CI = 1.306-2.028; p < 0.001) were significantly and independently associated with a duration of recovery within 14 days. The SMOTEEN/RF algorithm performed best, with an accuracy of 90.32%, sensitivity of 92.22%, specificity of 88.31%, F1 score of 90.71%, and AUC of 89.75% for the 7-day recovery prediction; and an accuracy of 93.81%, sensitivity of 93.40%, specificity of 93.81%, F1 score of 93.42%, and AUC of 93.53% for the 14-day recovery prediction. Conclusion: Age and vaccination dose were factors robustly associated with accelerated recovery both on day 7 and day 14 from the onset of disease during the Omicron BA. 2.2 wave. The results suggest that the SMOTEEN/RF-based model could be used to predict the probability of 7-day and 14-day recovery from the Omicron variant of SARS-CoV-2 infection for COVID-19 prevention and control policy in other regions or countries. This may also help to generate external validation for the model.

Cryo-EM structures reveal the activation and substrate recognition mechanism of human enteropeptidase.

Enteropeptidase (EP) initiates intestinal digestion by proteolytically processing trypsinogen, generating catalytically active trypsin. EP dysfunction causes a series of pancreatic diseases including acute necrotizing pancreatitis. However, the molecular mechanisms of EP activation and substrate recognition remain elusive, due to the lack of structural information on the EP heavy chain. Here, we report cryo-EM structures of human EP in inactive, active, and substrate-bound states at resolutions from 2.7 to 4.9 Å. The EP heavy chain was observed to clamp the light chain with CUB2 domain for substrate recognition. The EP light chain N-terminus induced a rearrangement of surface-loops from inactive to active conformations, resulting in activated EP. The heavy chain then served as a hinge for light-chain conformational changes to recruit and subsequently cleave substrate. Our study provides structural insights into rearrangements of EP surface-loops and heavy chain dynamics in the EP catalytic cycle, advancing our understanding of EP-associated pancreatitis.

Bacillus subtilis Attenuates Hepatic and Intestinal Injuries and Modulates Gut Microbiota and Gene Expression Profiles in Mice Infected with Schistosoma japonicum.

Parasitic infection can induce pathological injuries and impact the gut microbiota diversity and composition of the host. Bacillus subtilis is a nonpathogenic and noninvasive probiotic bacterium for humans and other animals, playing an important role in improving the host immune system's ability to respond to intestinal and liver diseases and modulating gut microbiota. However, whether B. subtilis can impact biological functions in Schistosoma japonicum-infected mice is unclear. This study used oral administration (OA) of B. subtilis to treat mice infected with S. japonicum. We evaluated changes in the gut microbiota of infected mice using 16 S rRNA gene sequencing and differentially expressed gene profiles using transcriptome sequencing after OA B. subtilis. We found that OA B. subtilis significantly attenuated hepatic and intestinal pathological injuries in infected mice. The gut microbiota of mice were significantly altered after S. japonicum infection, while OA B. subtilis remodel the diversity and composition of gut microbiomes of infected mice. We found that the S. japonicum-infected mice with OA B. subtilis had an overabundance of the most prevalent bacterial genera, including Bacteroides, Enterococcus, Lactobacillus, Blautia, Lachnoclostridium, Ruminiclostridium, and Enterobacter. Transcriptomic analysis of intestinal tissues revealed that OA B. subtilis shaped the intestinal microenvironment of the host responding to S. japonicum infection. Differentially expressed genes were classified into KEGG pathways between S. japonicum-infected mice and those without included cell adhesion molecules, intestinal immune network for IgA production, hematopoietic cell lineage, Fc epsilon RI signaling pathway, Th1 and Th2 cell differentiation, Th17 cell differentiation, calcium signaling pathway, Fc gamma R-mediated phagocytosis, chemokine signaling pathway, phospholipase D signaling pathway, NF-kappa B signaling pathway, B cell receptor signaling pathway, pancreatic secretion, and phagosome. In conclusion, our findings showed that OA B. subtilis alleviates pathological injuries and regulates gene expression, implying that B. subtilis supplementation may be a potential therapeutic strategy for schistosomiasis. Our study may highlight the value of probiotics as a beneficial supplementary therapy during human schistosomiasis, but further studies are needed.

An immunoscore nomogram for predicting survival in patients with oesophageal cancer.

This study aimed to construct and validate an immunoscore nomogram that may be used to predict the prognosis of oesophageal cancer. With the gene expression data of oesophageal cancer in a public database, we used CIBERSORT to estimate the fractions of 22 infiltrating immune cell types. We then built an immunoscore signature based on 12 types of infiltrating immune cells using the least absolute shrinkage and selection operator (LASSO) model. This immunoscore was used as an independent predictor in the prognostic model (training cohort: [hazard ratio (HR), 4.78; 95% confidence interval (CI), 2.64-8.67; P < 0.001], validation cohort: [HR, 2.15; 95% CI, 1.04-4.45; P = 0.040]). Subgroup analysis by clinical features showed that overall survival was significantly different between the high-immunoscore group and the low-immunoscore group. The predictors that constituted the individualized prediction nomogram were immunoscore, age, and tumour stage. The nomogram had good discrimination and calibration. Decision curve analysis showed that the immunoscore nomogram was clinically useful. Therefore, the novel immunoscore signature based on infiltrating immune cells can be used as a reliable predictor of the prognosis of oesophageal cancer, and the immunoscore nomogram is a convenient tool for predicting the survival of individual patients.

Comparison of the efficacy of hematopoietic stem cell mobilization regimens: a systematic review and network meta-analysis of preclinical studies.

BACKGROUND: Mobilization failure may occur when the conventional hematopoietic stem cells (HSCs) mobilization agent granulocyte colony-stimulating factor (G-CSF) is used alone, new regimens were developed to improve mobilization efficacy. Multiple studies have been performed to investigate the efficacy of these regimens via animal models, but the results are inconsistent. We aim to compare the efficacy of different HSC mobilization regimens and identify new promising regimens with a network meta-analysis of preclinical studies. METHODS: We searched Medline and Embase databases for the eligible animal studies that compared the efficacy of different HSC mobilization regimens. Primary outcome is the number of total colony-forming cells (CFCs) in per milliliter of peripheral blood (/ml PB), and the secondary outcome is the number of Lin- Sca1+ Kit+ (LSK) cells/ml PB. Bayesian network meta-analyses were performed following the guidelines of the National Institute for Health and Care Excellence Decision Support Unit (NICE DSU) with WinBUGS version 1.4.3. G-CSF-based regimens were classified into the SD (standard dose, 200-250 µg/kg/day) group and the LD (low dose, 100-150 µg/kg/day) group based on doses, and were classified into the short-term (2-3 days) group and the long-term (4-5 days) group based on administration duration. Long-term SD G-CSF was chosen as the reference treatment. Results are presented as the mean differences (MD) with the associated 95% credibility interval (95% CrI) for each regimen. RESULTS: We included 95 eligible studies and reviewed the efficacy of 94 mobilization agents. Then 21 studies using the poor mobilizer mice model (C57BL/6 mice) to investigate the efficacy of different mobilization regimens were included for network meta-analysis. Network meta-analyses indicated that compared with long-term SD G-CSF alone, 14 regimens including long-term SD G-CSF + Me6, long-term SD G-CSF + AMD3100 + EP80031, long-term SD G-CSF + AMD3100 + FG-4497, long-term SD G-CSF + ML141, long-term SD G-CSF + desipramine, AMD3100 + meloxicam, long-term SD G-CSF + reboxetine, AMD3100 + VPC01091, long-term SD G-CSF + FG-4497, Me6, long-term SD G-CSF + EP80031, POL5551, long-term SD G-CSF + AMD3100, AMD1300 + EP80031 and long-term LD G-CSF + meloxicam significantly increased the collections of total CFCs. G-CSF + Me6 ranked first among these regimens in consideration of the number of harvested CFCs/ml PB (MD 2168.0, 95% CrI 2062.0-2272.0). In addition, 7 regimens including long-term SD G-CSF + AMD3100, AMD3100 + EP80031, long-term SD G-CSF + EP80031, short-term SD G-CSF + AMD3100 + IL-33, long-term SD G-CSF + ML141, short-term LD G-CSF + ARL67156, and long-term LD G-CSF + meloxicam significantly increased the collections of LSK cells compared with G-CSF alone. Long-term SD G-CSF + AMD3100 ranked first among these regimens in consideration of the number of harvested LSK cells/ml PB (MD 2577.0, 95% CrI 2422.0-2733.0). CONCLUSIONS: Considering the number of CFC and LSK cells in PB as outcomes, G-CSF plus AMD3100, Me6, EP80031, ML141, FG-4497, IL-33, ARL67156, meloxicam, desipramine, and reboxetine are all promising mobilizing regimens for future investigation.

Efficacy and safety of new anti-CD20 monoclonal antibodies versus rituximab for induction therapy of CD20+ B-cell non-Hodgkin lymphomas: a systematic review and meta-analysis.

Rituximab combined with chemotherapy is the first-line induction therapy of CD20 positive B-cell non-Hodgkin lymphomas (CD20+ B-NHL). Recently new anti-CD20 monoclonal antibodies (mAbs) have been developed, but their efficacy and safety compared with rituximab are still controversial. We searched MEDLINE, Embase, and Cochrane Library for eligible randomized controlled trials (RCTs) that compared new anti-CD20 mAbs with rituximab in induction therapy of B-NHL. The primary outcomes are progression-free survival (PFS) and overall survival (OS), additional outcomes include event-free survival (EFS), disease-free survival (DFS), overall response rate (ORR), complete response rate (CRR) and incidences of adverse events (AEs). Time-to-event data were pooled as hazard ratios (HRs) using the generic inverse-variance method and dichotomous outcomes were pooled as odds ratios (ORs) using the Mantel-Haenszel method with their respective 95% confidence interval (CI). Eleven RCTs comprising 5261 patients with CD20+ B-NHL were included. Compared with rituximab, obinutuzumab significantly prolonged PFS (HR 0.84, 95% CI 0.73-0.96, P = 0.01), had no improvement on OS, ORR, and CRR, but increased the incidences of serious AEs (OR 1.29, 95% CI 1.13-1.48, P < 0.001). Ofatumumab was inferior to rituximab in consideration of ORR (OR 0.73, 95% CI 0.55-0.96, P = 0.02), and had no significant differences with rituximab in regard to PFS, OS and CRR. 131I-tositumomab yielded similar PFS, OS, ORR and CRR with rituximab. 90Y-ibritumomab tiuxetan increased ORR (OR 3.07, 95% CI 1.47-6.43, P = 0.003), but did not improve PFS, DFS, OS and CRR compared with rituximab. In conclusion, compared with rituximab in induction therapy of CD20+ B-NHL, obinutuzumab significantly improves PFS but with higher incidence of AEs, ofatumumab decreases ORR, 90Y-ibritumomab tiuxetan increases ORR.

Prognostic Significance of CD56 Antigen Expression in Patients with De Novo Non-M3 Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a heterogeneous group of disorders with distinct characteristics and prognoses. Although cytogenetic changes and gene mutations are associated with AML prognosis, there is a need to identify further factors. CD56 is considered a prognostic factor for AML, which is abnormally expressed in leukemia cells. However, a clear consensus for this surface molecule is lacking, which has prompted us to investigate its prognostic significance. Bone marrow samples of de novo non-M3 AML were collected to detect CD56 expression using multiparameter flow cytometry (FCM). As a result, the CD56 expression in de novo non-M3 AML was found to be significantly higher than that in acute lymphoma leukemia (ALL, P = 0.017) and healthy controls (P = 0.02). The X-Tile program produced a CD56 cutoff point at a relative expression level of 24.62%. Based on this cutoff point, high CD56 expression was observed in 29.21% of de novo non-M3 AML patients. CD56-high patients had a poor overall survival (OS, P = 0.015) compared to CD56-low patients. Bone marrow transplantation (BMT) improved OS (P = 0.004), but a poor genetic risk was associated with an inferior OS (P = 0.002). Compared with CD56-low patients, CD56-high patients had lower peripheral blood platelet (PLT) counts (P = 0.010). Our research confirmed that high CD56 expression is associated with adverse clinical outcomes in de novo non-M3 AML patients, indicating that CD56 could be used as a prognostic marker for a more precise stratification of de novo non-M3 AML patients.

Gut Microbiota Modulates Intestinal Pathological Injury in Schistosoma japonicum-Infected Mice.

Trapping of Schistosoma japonicum (S. japonicum) eggs in host tissue, mainly in the intestine and liver, causes severe gastrointestinal and hepatic granulomatous immune responses and irreversible fibrosis. Although the gut microbiota plays a central role in regulating pathological responses in several diseases, the effect of the gut microbiota on the pathologenesis progression of schistosomiasis remains largely unknown. In this study, we aimed to investigate the regulatory function of the gut microbiota in schistosomiasis japonica. We found that the depletion of the gut microbiota significantly ameliorated egg granulomas formation and fibrosis in the intestine of infected mice. This role of the gut microbiota in intestinal granuloma formation and fibrosis was reinforced when normal and infected mice were housed together in one cage. Notably, changes in the gut microbiota induced by S. japonicum infection were partly reversible with microbiota transfer in the cohousing experiment. Transfer of the gut microbiota from normal to infected mice attenuated the intestinal pathological responses. Depletion of the gut microbiota by antibiotics, or transfer of the gut microbiota from normal to infected mice decreased the levels of IL-4, IL-5, and IL-13 and promoted the production of cytokines and mRNA levels of IL-10 and TGF-ß in infected mice. Our findings indicated a regulatory effect of the gut microbiota on intestinal pathological injury associated with schistosomiasis japonica in mice, and thus suggested a potential strategy for schistosomiasis treatment.

Cumulative Evidence for Associations between Genetic Variants and Risk of Esophageal Cancer.

BACKGROUND: A large number of studies have been conducted to investigate associations between genetic variants and esophageal cancer risk in the past several decades. However, findings from these studies have been generally inconsistent. We aimed to provide a summary of the current understanding of the genetic architecture of esophageal cancer susceptibility. METHODS: We performed a comprehensive field synopsis and meta-analysis to evaluate associations between 95 variants in 70 genes or loci and esophageal cancer risk using data from 304 eligible publications, including 104,904 cases and 159,797 controls, through screening a total of 21,328 citations. We graded levels of cumulative epidemiologic evidence of a significant association with esophageal cancer using the Venice criteria and false-positive report probability tests. We constructed functional annotations for these variants using data from the Encyclopedia of DNA Elements Project and other databases. RESULTS: Thirty variants were nominally significantly associated with esophageal cancer risk. Cumulative epidemiologic evidence of a significant association with overall esophageal cancer, esophageal squamous cell carcinoma, or esophageal adenocarcinoma was strong for 13 variants in or near 13 genes (ADH1B, BARX1, CDKN1A, CHEK2, CLPTM1L, CRTC1, CYP1A1, EGF, LTA, MIR34BC, PLCE1, PTEN, and PTGS2). Bioinformatics analysis suggested that these variants and others correlated with them might fall in putative functional regions. CONCLUSIONS: Our study summarizes the current literature on the genetic architecture of esophageal cancer susceptibility and identifies several potential polymorphisms that could be involved in esophageal cancer susceptibility. IMPACT: These findings provide direction for future studies to identify new genetic factors for esophageal cancer.