Animal models have indicated that intestinal microbiota influence acute graft-versus-host disease (aGVHD) by modulating immune homeostasis. But, in humans, the mechanism by which the microbiota induces aGVHD remains unclear. In this study, we investigated the relationship between the intestinal microbiota and T cell subsets in patients who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT) to explore the mechanism by which microbiota induced aGVHD. Based on aGVHD, this study was categorized into two groups: grades II–IV aGVHD (aGVHD group, n = 32) and grade 0–I aGVHD (non-aGVHD group, n = 49). The intestinal microbiota was detected by 16S rRNA gene sequencing, and the T cell subsets and histone 3 (H3) acetylation in CD4+ T cells in the peripheral blood was assayed by flow cytometry at the time of engraftment. The aGVHD group had greater low microbial diversity than the non-aGVHD group (56.3 versus 24.5%, p = 0.004). The bacterial community was depleted of Clostridia (e.g., the Lachnospiraceae and Ruminococcaceae families) and enriched for Gammaproteobacteria (e.g., the Enterobacteriaceae family) in the aGVHD group compared with the non-aGVHD group. The relative abundance of Lachnospiraceae and Ruminococcaceae was positively correlated with the Treg/Th17 ratio counts (r = 0.469 and 0.419; p < 0.001 and <0.001, respectively), whereas Enterobacteriaceae was negatively correlated with the Treg/Th17 ratio (r = −0.277; p = 0.012). The level of acetylated H3 in CD4+ T cells was not only correlated with Lachnospiraceae/Ruminococcaceae, but also with the Treg/Th17 ratio (r = 0.354; p = 0.001). In conclusions, our results suggest that decreased Lachnospiraceae and Ruminococcaceae and increased Enterobacteriaceae, correlate with a Treg/Th17 imbalance, which might be through acetylated H3 in CD4+ T cells. These findings suggest that intestinal microbiota might induce aGVHD by influencing the Treg/Th17 balance.

Inflammation-based prognostic scores, such as the glasgow prognostic score (GPS), prognostic index (PI), prognostic nutritional index (PNI), neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) were related to survival in many solid tumors. Recent study showed that GPS can be used to predict outcome in diffuse large B-cell lymphoma (DLBCL). However, other inflammation related scores had not been reported and it also remained unknown which of them was the most useful to evaluate the survival in DLBCLs. In this retrospective study, a number of 252 newly diagnosed and histologically proven DLBCLs from January 2003 to December 2014 were included. The high GPS, high PI, high NLR, high PLR and low PNI were all associated with poor overall survival (p < 0.05) and event-free survival (p < 0.05) in univariate analysis. Multivariate analysis indicated that GPS (HR = 1.781, 95% CI = 1.065–2.979, p = 0.028) remained an independent prognostic predictor in DLBCL. The c-index of GPS (0.735, 95% CI = 0.645–0.824) was greater than that of PI (0.710, 95% CI = 0.621–0.799, p = 0.602), PNI (0.600, 95% CI = 0.517–0.683, p = 0.001), PLR (0.599, 95% CI = 0.510–0.689, p = 0.029) and NLR (0.572, 95% CI = 0.503–0.642, p = 0.005) by Harrell's concordance index. Especially in DLBCLs treated with R-CHOP, GPS still remained the most powerful prognostic score when comparing with others (p = 0.001 and p < 0.001, respectively for OS and EFS). In conclusion, it is indicated that inflammation-based prognostic scores such as GPS, PI, NLR, PNI and PLR all could be used to predict the outcome of DLBCLs. Among them, GPS is the most powerful indicator in predicting survival in DLBCLs, even in the rituximab era.

Purpose Neuropathic pain is an unavoidable treatment-related adverse event among patients with head and neck cancer who are undergoing radiotherapy. We aimed to test the efficacy and safety of pregabalin versus placebo in the treatment of radiotherapy-related neuropathic pain. Patients and Methods This randomized, double-blind, placebo-controlled trial was conducted in four centers in China. Eligible patients with a mean pain intensity score of 4 or more on an 11-point numeric rating scale were randomly assigned to receive either active treatment with a flexible dose of pregabalin or placebo for 16 weeks. The primary efficacy outcome was pain reduction measured on the numeric rating scale. Result There were 128 patients who received treatment as randomly assigned. Pain intensity reduction was 2.44 in the pregabalin arm and 1.58 in the placebo arm at week 16, yielding an adjusted mean difference of 0.87 (95% CI, 0.30 to 1.44; P = .003). In the pregabalin arm, 38 patients (59.4%) achieved at least 30% pain relief versus 21 (32.8%) in the placebo arm ( P = .006). Nineteen patients (29.7%) in the pregabalin group and five (7.8%) in the placebo group achieved 50% or greater pain relief ( P = .003). Total scores on the Profile of Mood States-Short Form, pain severity and functional interference of Brief Pain Inventory-Short Form, as well as the physiology and psychology domain of the WHO Quality of Life-BREF all were reduced significantly at week 16 in patients who received pregabalin compared with those who received placebo. There was no significant difference ( P = .29) in the incidence of experiencing at least one adverse event in the pregabalin arm (n = 35; 54.7%) versus the placebo arm (n = 29; 45.3%). Conclusion Patients treated with pregabalin with radiotherapy-related neuropathic pain had greater pain alleviation, better mood states, and higher quality of life compared with patients in the placebo group, with a good tolerability.

The emergence of numerous variants of SARS-CoV-2, the causative agent of COVID-19, has presented new challenges to the global efforts to control the COVID-19 pandemic. Here, we obtain two cross-neutralizing antibodies (7D6 and 6D6) that target Sarbecoviruses’ receptor-binding domain (RBD) with sub-picomolar affinities and potently neutralize authentic SARS-CoV-2. Crystal structures show that both antibodies bind a cryptic site different from that recognized by existing antibodies and highly conserved across Sarbecovirus isolates. Binding of these two antibodies to the RBD clashes with the adjacent N-terminal domain and disrupts the viral spike. Both antibodies confer good resistance to mutations in the currently circulating SARS-CoV-2 variants. Thus, our results have direct relevance to public health as options for passive antibody therapeutics and even active prophylactics. They can also inform the design of pan-sarbecovirus vaccines.

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ObjectivesTo assess the additional detection rate (ADR) of within-patient comparisons of Narrow band imaging (NBI) and white light cystoscopy (WLC) for non-muscle invasive bladder cancer (NMIBC) detection and compare the impact of NBI and WLC on bladder cancer recurrence risk.MethodsWe searched relevant studies from PubMed, Embase, Medline, Web of Science and the Cochrane Library database for all articles in English published beforeJuly26th, 2016. Pooled ADR, diagnostic accuracy, relative risk (RR) and their 95% confidence intervals (CIs) were calculated.ResultsTwenty-five studies including 17 full texts and eight meeting abstracts were included for analysis. Compared to WLC, pooled ADR of NBI for NMIBC diagnosis was 9.9% (95% CI: 0.05–0.14) and 18.6% (95% CI: 0.15–0.25) in per-patient and per-lesion analysis, respectively. Pooled ADR of NBI for carcinoma in situ (CIS) diagnosis was 25.1% (95% CI: 0.09–0.42) and 31.1% (95% CI: 0.24–0.39) for per-patient and per-lesion analyses, respectively. The pooled sensitivity of NBI was significantly higher than WLC both at the per-patient (95.8% vs. 81.6%) and per-lesion levels (94.8% vs. 72.4%). In addition, NBI significantly reduced the recurrence rate of bladder cancer with a pooled RR value of 0.43 (95% CI: 0.23–0.79) and0.81 (95% CI: 0.69–0.95) at month three and twelve, respectively.ConclusionsNBI is a valid technique that improves the diagnosis of NMIBC and CIS compared to standard WLC either at per-patient or per-lesion level. It can reduce the recurrence rate of bladder cancer accordingly.

The intestinal microbiome plays an important role in the development of acute graft-versus-host disease (aGVHD). However, whether intestinal microbiota can predict the development of aGVHD has been reported only rarely. Here we conducted a prospective study of microbiota in 141 patients after allogeneic hematopoietic stem cell transplantation. We found lower microbiota diversity in the aGVHD group compared with the non-aGVHD group at day 0 and day 15 § 1 (P = .018 and .009, respectively). Diversity was negatively associated with conditioning intensity (P = .017, day 0; P = .045, day 15) and b-lactam antibiotic administration (P = .004, day 15). Intensified conditioning and b-lactam antibiotics were associated with a lower regulatory T (Treg)/T helper 17 (Th17) cell ratio at day 15 (P = .030 and .047, respectively). At day 15, the levels of the inflammatory factors (tumor necrosis factor a, interleukin [IL]-6, IL-17A, IL-1b, and lipopolysaccharide) were higher in the intensified conditioning group compared with the standard group (P < .05). The accumulated intestinal microbiota (AIM) score was defined as microbiota diversity and gradient of the 4 bacterials (Lachnospiraceae, Peptostreptococcaceae, Erysipelotrichaceae, and Enterobacteriaceae) at day 15 post-transplantation. The AIM score was positively correlated with aGVHD grade (r = .481, P < .001), and the AIM score could be predictive of the development of aGVHD (grade II-IV aGVHD: area under the curve [AUC], .75, P < .001; grade III-IV aGVHD: AUC, .84, P < .001). These findings suggest that intestinal microbiota and conditioning might induce aGVHD by inflammatory factors and the Treg/Th17 balance. The constitution of the intestinal microbiota at neutrophil engraftment may predict the development of aGVHD.

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