Background Commensal microbiota play a critical role in maintaining oral tolerance. The effect of food allergy on the gut microbial ecology remains unknown. Objective We sought to establish the ...composition of the gut microbiota in experimental food allergy and its role in disease pathogenesis. Methods Food allergy–prone mice with a gain-of-function mutation in the IL-4 receptor α chain ( Il4raF709 ) and wild-type (WT) control animals were subjected to oral sensitization with chicken egg ovalbumin (OVA). Enforced tolerance was achieved by using allergen-specific regulatory T (Treg) cells. Community structure analysis of gut microbiota was performed by using a high-density 16S rDNA oligonucleotide microarrays (PhyloChip) and massively parallel pyrosequencing of 16S rDNA amplicons. Results OVA-sensitized Il4raF709 mice exhibited a specific microbiota signature characterized by coordinate changes in the abundance of taxa of several bacterial families, including the Lachnospiraceae, Lactobacillaceae, Rikenellaceae, and Porphyromonadaceae. This signature was not shared by similarly sensitized WT mice, which did not exhibit an OVA-induced allergic response. Treatment of OVA-sensitized Il4raF709 mice with OVA-specific Treg cells led to a distinct tolerance-associated signature coincident with the suppression of the allergic response. The microbiota of allergen-sensitized Il4raF709 mice differentially promoted OVA-specific IgE responses and anaphylaxis when reconstituted in WT germ-free mice. Conclusion Mice with food allergy exhibit a specific gut microbiota signature capable of transmitting disease susceptibility and subject to reprogramming by enforced tolerance. Disease-associated microbiota may thus play a pathogenic role in food allergy.
Abstract Background So far, relatively few studies have addressed the use of stem cells to treat patients with refractory angina. Moreover, the results of current studies were discrepant. The ...objective of this meta-analysis was to evaluate the efficacy and safety of this treatment on a relatively large scale. Methods Studies were identified through PubMed, CENTRAL, EMBASE, reviews, and reference lists of relevant papers. The weighted mean difference was calculated with random-effect models for net changes in exercise tolerance and angina frequency, and odds ratio (OR) with fixed-effect models for myocardial infarction (MI) and death. Results Five randomized controlled trials, with a total of 381 patients, were included in the analysis. Compared with the controls, patients who received stem cell therapy had a significant improvement in exercise tolerance of 61.3 seconds (95% confidence interval CI, 18.1-104.4; P = 0.005; I2 = 58%); an obvious reduction in angina frequency of 7.3 episodes per week (95% CI, −13.4 to −1.2; P = 0.02; I2 = 93%); and lower risk of MI, with an OR of 0.37 (95% CI, 0.14-0.95; P = 0.04; I2 = 0%). No difference was detected for the risk of death (OR, 0.33; 95% CI, 0.08-1.39; P = 0.13; I2 = 20%). Conclusions Stem cell therapy appears to be effective and safe in the management of patients with refractory angina. The findings need confirmation in larger-scale studies with longer follow-up.
Summary Background China is experiencing growing epidemics of HIV and sexually transmitted infections (STIs). Programmes to train physicians in China on HIV and STI knowledge, diagnosis, treatment, ...and risk reduction counselling can potentially reduce HIV and STI risk among high-risk patients. We aimed to assess a knowledge-based and skills-based programme for physicians in China to reduce patients' STI risk. Methods In this cluster randomised trial, we block randomised counties in two provinces in eastern China to intervention or control groups. In the intervention group, physicians from county general hospitals participated in a structured HIV and STI training programme and received opportunities to enhance their clinical and counselling skills, whereas in the control group, physicians from county hospitals received the training after the intervention group completed final assessments. We recruited STI patients from physicians in both groups, treated baseline gonorrhoea and chlamydia infections, and assessed 9-month gonorrhoea and chlamydia reinfection as the primary outcome. Statistical comparisons between intervention and delayed-control patients used multilevel analyses to account for cluster effects at county and physician levels. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov , NCT00644150. Findings Between April 1, 2007, and Sept 1, 2008, 51 counties were randomly assigned; 27 to receive immediate intervention and 24 to receive delayed intervention. 249 physicians from the 51 county-level hospitals were enrolled, 121 physicians in the intervention group and 128 in the control group. From these physicians, we enrolled 633 and 491 patients, respectively, of whom 508 (80%) and 402 (82%) were available for reassessment at 9 months. Intervention patients at follow-up had significantly lower odds of combined gonorrhoea or chlamydia reinfection than did control patients (58/508 11% vs 123/402 31%; adjusted odds ratio 0·62 95% CI 0·46–0·84). Interpretation Integrating HIV and STI training into medical education in China could be an effective strategy to reduce the country's growing HIV risk and STI epidemics. Funding US National Institutes of Health.
Abstract Introduction The aim of this study was to investigate the release of growth factors into root canal space after the irrigation procedure of regenerative endodontic procedure. Methods Sixty ...standardized root segments were prepared from extracted single-root teeth. Nail varnish was applied to all surfaces except the root canal surface. Root segments were irrigated with 1.5% NaOCl + 17% EDTA, 2.5% NaOCl + 17% EDTA, 17% EDTA, or deionized water. The profile of growth factors that were released after irrigation was studied by growth factor array. Enzyme-linked immunosorbent assay was used to validate the release of transforming growth factor (TGF)-β1 and basic fibroblast growth factor (bFGF) at 4 hours, 1 day, and 3 days after irrigation. The final concentrations were calculated on the basis of the root canal volume measured by cone-beam computed tomography. Dental pulp stem cell migration on growth factors released from root segments was measured by using Transwell assay. Results Total of 11 of 41 growth factors were detected by growth factors array. Enzyme-linked immunosorbent assay showed that TGF-β1 was released in all irrigation groups. Compared with the group with 17% EDTA (6.92 ± 4.49 ng/mL), the groups with 1.5% NaOCl + 17% EDTA and 2.5% NaOCl + 17% EDTA had significantly higher release of TGF-β1 (69.04 ± 30.41 ng/mL and 59.26 ± 3.37 ng/mL, respectively), with a peak release at day 1. The release of bFGF was detected at a low level in all groups (0 ng/mL to 0.43 ± 0.22 ng/mL). Migration assay showed the growth factors released from root segments induced dental pulp stem cell migration. Conclusions The root segment model in present study simulated clinical scenario and indicated that the current irrigation protocol released a significant amount of TGF-β1 but not bFGF. The growth factors released into root canal space induced dental pulp stem cell migration.
Vanadium, an important pollutant produced from anthropogenic activities, has been suggested to be embryotoxic and fetotoxic in animal studies. However, little is known about its effects on humans. We ...aimed to assess the association of prenatal exposure to vanadium with the risk of adverse birth outcomes in babies born to women in China.
For this population-based cohort study, the Healthy Baby Cohort, women were recruited from three cities in Hubei Province, China. Women included in this analysis were recruited from Wuhan Women and Children Medical Care Center, Wuhan. We measured urinary concentrations of vanadium and other metals simultaneously using inductively coupled plasma mass spectrometry. We used multivariable logistic regressions, with adjustment for potential confounders, to estimate the associations of natural logarithm transformed creatinine-corrected urinary vanadium (Ln-vanadium) concentrations as continuous variables and categorised into quartiles (Q; Q1: ≤0·84 μg/g creatinine, Q2: 0·84–1·40 μg/g creatinine, Q3: 1·40–2·96 μg/g creatinine, Q4: >2·96 μg/g creatinine, with the lowest quartile set as reference) with preterm delivery, early-term delivery, low birthweight, and being small for gestational age. We applied restricted cubic spline models to evaluate the dose-response relationships.
Data from 7297 women recruited between Sept 22, 2012, and Oct 22, 2014, were included in this study. Urinary Ln-vanadium concentrations showed non-linear dose-response relationships with risk of preterm delivery (S-shaped, p<0·0001) and low birthweight (J-shaped, p=0·0001); the adjusted odds ratios (ORs) for increasing quartiles of urinary vanadium were 1·76 (95% CI 1·05–2·95) for Q2, 3·17 (1·96–5·14) for Q3, and 8·86 (5·66–13·86) for Q4 for preterm delivery, and 2·29 (95% CI 1·08–4·84) for Q2, 3·22 (1·58–6·58) for Q3, and 3·56 (1·79–7·10) for Q4 for low birthweight. Ln-vanadium concentrations were linearly associated with the risk of early-term delivery (linear, p<0·0001) and being small for gestational age (linear, p=0·0027), with adjusted ORs of 1·15 (95% CI 1·10–1·21) for early-term delivery and 1·12 (1·04–1·21) for being small for gestational age per unit increase in Ln-vanadium concentrations.
Our findings reveal a relationship between prenatal exposure to higher levels of vanadium and increased risk of adverse birth outcomes, suggesting that vanadium might be a potential toxic metal for human beings. Further studies are needed to replicate the observed associations and investigate the interaction effects of prenatal exposure to different metals on adverse birth outcomes.
National Key R&D Plan of China, National Natural Science Foundation of China, and Fundamental Research Funds for the Central Universities, Key Laboratory of Environment and Health.
Abstract Purpose Resistance to the antiemetic ondansetron is still a major problem resulting in discomfort and poor compliance with chemotherapy in acute myeloid leukemia (AML) patients. Based on our ...hypothesis that this clinical resistance to ondansetron is associated with ABCB1 genetic polymorphisms, we investigated whether ABCB1 gene variations affect the efficacy of ondansetron in chemotherapy-induced nausea and vomiting. Methods AML patients (n = 215) treated for 3 days with high-dose cytarabine were enrolled in this study. Thirty minutes before the beginning of chemotherapy, 8 mg ondansetron was administered intravenously, followed by 24 mg by continuous infusion and 8 mg intravenously, once per day, until 2 days after chemotherapy. Chemotherapy-induced nausea and vomiting occurrence in the acute and delayed phases was calculated. ABCB1 and CYP2D6 polymorphisms were analyzed by allele-specific matrix-assisted laser desorption. Basic clinical characteristics of the AML patients were collected from medical records. Findings No differences in genotype distribution frequencies of ABCB1 polymorphisms and haplotypes were observed in patients with different CYP2D6 -predicted phenotypes. During the acute phase, patients with the CG haplotype (C3435T and G2677T) were associated with a high risk of grade 3/4 nausea and vomiting ( P = 0.003 and P = 0.026, respectively). After adjustment for age, sex, smoking status, alcohol drinking status, body surface area, body mass index, and Eastern Cooperative Oncology Group−Performance Status, multivariate survival analysis implicated the CG haplotype as a predictive marker of the risk of grade 3/4 chemotherapy-induced nausea and vomiting in AML patients ( P = 0.003 and P = 0.039, respectively). In addition, a significant association between the 3435CC genotype and grade 3/4 vomiting in AML patients was observed ( P = 0.016). However, no association between these ABCB1 gene polymorphisms and ondansetron efficacy was found in the delayed phase. Implications These findings suggest that ABCB1 gene polymorphisms are associated with antiemetic efficacy of ondansetron in the acute phase after high-dose cytarabine chemotherapy in AML patients.
The aim of this meta-analysis was to comprehensively evaluate the effectiveness of Diagnosis-related group (DRG) based payment on inpatient quality of care. A comprehensive literature search was ...conducted in PubMed, EMBASE, Cochrane Central Register of Controlled Trials and Web of Science from their inception to December 30, 2022. Included studies reported associations between DRGs-based payment and length of stay (LOS), re-admission within 30 days and mortality. Two reviewers screened the studies independently, extracted data of interest and assessed the risk of bias of eligible studies. Stata 13.0 was used in the meta-analysis. A total of 29 studies with 36 214 219 enrolled patients were analyzed. Meta-analysis showed that DRG-based payment was effective in LOS decrease (pooled effect: SMD = −0.25, 95% CI = −0.37 to −0.12, Z = 3.81, P < .001), but showed no significant overall effect in re-admission within 30 days (RR = 0.79, 95% CI = 0.62-1.01, Z = 1.89, P = .058) and mortality (RR = 0.91, 95% CI = 0.72-1.15, Z = 0.82, P = .411). DRG-based payment demonstrated statistically significant superiority over cost-based payment in terms of LOS reduction. However, owing to limitations in the quantity and quality of the included studies, an adequately powered study is necessary to consolidate these findings.
Introduction The role of SMU1 in DNA replication and RNA splicing is well-established, yet its specific function and dysregulated mechanisms in gastric cancer (GC) remain inadequately elucidated. ...This study seeks to investigate the potential oncogenic and progression-promoting effects of SMU1 in GC, with the ultimate goal of informing novel approaches for treatment and diagnosis. Methods The study investigated the expression levels of SMU1 in GC and adjacent normal tissues by analyzing data from the TCGA (27 tissue pairs) and GEO (47 tissue pairs) databases. Immunohistochemistry was used to examine 277 tumor tissue and adjacent non-tumor tissue spots from GC tissue chips, along with relevant follow-up information. The study further assessed the proliferation, invasion, and migration capabilities of cells by manipulating SMU1 expression levels and conducting various assays, including CCK-8, EdU incorporation, colony formation, transwells, flow cytometry, and subcutaneous tumorigenesis assays. Results Our study revealed a significant upregulation of SMU1 mRNA and protein levels in GC tissues compared to adjacent tissues. Univariate and multivariate Cox analysis demonstrated that elevated levels of SMU1 were independent prognostic factors for GC prognosis ( P = 0.036). Additionally, median survival analysis indicated a significant association between high SMU1 expression and poor prognosis in GC patients ( P = 0.0002). In experiments conducted both in vivo and in vitro, it was determined that elevated levels of SMU1 can enhance the proliferation, invasion, and migration of GC cells, whereas suppression of SMU1 can impede the progression of GC by modulating the G1/S checkpoint of the cell cycle. Conclusions Our research introduces the novel idea that SMU1 could serve as a prognostic marker for GC progression, influencing cell proliferation through cell cycle activation. These results offer valuable insights into the understanding, diagnosis, and management of gastric carcinoma.
Background: Malignant glioma is a lethal brain tumor that is highly resistant to standard therapy. Our research aims to explore the suppressive effects of nitidine chloride (NC) on gliomas and the ...mechanisms involved, showing that it is a potential agent for integrative therapy of gliomas. Methods: After glioma cells were treated with NC, several experiments were performed to evaluate NC’s antitumor effects. CCK-8 assay was used to detect viability. Transwell and 3-dimensional spheroid invasion assays were used to evaluate motility of glioma in vitro, and the sphere-formation assay showed NC’s influence on glioma stem cells. Apoptosis and intracellular reactive oxygen species were measured by means of flow cytometry. Subcellular structures were observed through transmission electron microscopy. Western blot analysis reflected expression of endoplasmic reticulum (ER) stress and epithelial-mesenchymal transition (EMT) marker proteins. An orthotopic xenograft model was established to investigate the tumor suppressive effects in vivo. Results: Nitidine chloride inhibited glioma cell migration and invasion in vitro, downregulated the EMT proteins, and suppressed sphere formation of glioma stem cells. Furthermore, NC induced persistent ER stress that contributed to apoptosis and reactive oxygen species production. The xenograft model showed that NC effectively restricted glioma growth and invasion in vivo. Furthermore, we confirmed the signaling pathways that ER stress downregulates C/EBPβ and slug, as well as inhibition of the AKT/GSK3β/β-catenin axis caused by NC, in U-87 MG. Conclusion: We demonstrated that NC inhibits gliomas in vitro and in vivo by activating ER stress and downregulating EMT, which provides a basis for glioma therapy.
Objective:
To describe the clinical and pathological features of endometrial carcinoma with extraperitoneal metastasis and examine whether surgery could improve the prognosis.
Methods:
The ...Surveillance, Epidemiology, and End Results database was used to analyze 730 patients who were diagnosed with extraperitoneal metastasis of endometrial cancer from 2010 to 2015, including metastasis to the lung, bone, or brain.
Results:
Of the 730 patients, 372 (50.96%) patients had single lung metastases, and 196(26.85%) patients had multiple organ metastases that included pulmonary invasion. Therefore, the lung was the most common target organ for extraperitoneal metastasis of endometrial cancer. In multivariate risk factor analysis, grade 3 tumor (odds ratio = 3.39, P < .001), positive peritoneal cytology (odds ratio = 2.02, P < .001), and cervical stromal invasion (odds ratio = 1.42, P = .030) were independent risk factors for extraperitoneal metastasis. Once metastasis occurred in the brain or multiple organs, the prognosis was often poor. Of the patients, 362 underwent surgery, and surgery was performed only for primary tumors of the reproductive organs in almost all patients (97.23%) with extraperitoneal metastasis. The median cancer-specific survival periods of patients with solitary pulmonary metastasis undergoing surgery and those without surgery were 23 (16.43-29.57) months and 9 (6.21-11.79) months, respectively (P < .001), and survival superiority also existed in patients with bone metastasis (19 vs 8 months, P = .015) and multiple organs metastases (15 vs 4 months, P < .001). However, patients with brain metastasis had the same median survival period in the 2 groups (6 months, P = .146).
Conclusions:
The lung was the most common target organ for extraperitoneal metastasis in patients with endometrial cancer. Surgery was associated with improved survival in women with extraperitoneal metastasis, except for patients with brain metastasis.
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