Flip a coin: cell senescence at the maternal-fetal interface†.

During pregnancy, cell senescence at the maternal-fetal interface is required for maternal well-being, placental development, and fetal growth. However, recent reports have shown that aberrant cell senescence is associated with multiple pregnancy-associated abnormalities, such as preeclampsia, fetal growth restrictions, recurrent pregnancy loss, and preterm birth. Therefore, the role and impact of cell senescence during pregnancy requires further comprehension. In this review, we discuss the principal role of cell senescence at the maternal-fetal interface, emphasizing its "bright side" during decidualization, placentation, and parturition. In addition, we highlight the impact of its deregulation and how this "dark side" promotes pregnancy-associated abnormalities. Furthermore, we discuss novel and less invasive therapeutic practices associated with the modulation of cell senescence during pregnancy.

Evidence of cure for extranodal nasal-type natural killer/T-cell lymphoma with current treatment: an analysis of the CLCG database.

Survival from extranodal nasal-type NK/T-cell lymphoma (ENKTCL) has substantially improved over the last decade. However, there is little consensus as to whether a population of patients with ENKTCL can be considered "cured" of the disease. We aimed to evaluate the statistical "cure" of ENKTCL in the modern treatment era. This retrospective multicentric study reviewed the clinical data of 1,955 patients with ENKTCL treated with non-anthracycline-based chemotherapy and/or radiotherapy in the China Lymphoma Collaborative Group multicenter database between 2008 and 2016. A non-mixture cure model with incorporation of background mortality was fitted to estimate cure fractions, median survival times and cure time points. The relative survival curves attained plateau for the entire cohort and most subsets, indicating that the notion of cure was robust. The overall cure fraction was 71.9%. The median survival was 1.1 years in uncured patients. The cure time was 4.5 years, indicating that beyond this time, mortality in ENKTCL patients was statistically equivalent to that in the general population. Cure probability was associated with B symptoms, stage, performance status, lactate dehydrogenase, primary tumor invasion, and primary upper aerodigestive tract site. Elderly patients (>60 years) had a similar cure fraction to that of younger patients. The 5-year overall survival rate correlated well with the cure fraction across risk-stratified groups. Thus, statistical cure is possible in ENKTCL patients receiving current treatment strategies. Overall probability of cure is favorable, though it is affected by the presence of risk factors. These findings have a high potential impact on clinical practice and patients' perspective.

UHRF1 shapes both the trophoblast invasion and decidual macrophage differentiation in early pregnancy.

Trophoblasts play critical roles in establishment and maintenance of a normal pregnancy. Their dysfunction in early pregnancy is closely related to pregnancy-related diseases, including recurrent pregnancy loss (RPL). Epigenetic modifications dynamically change during pregnancy; however, the role of the epigenetic modifier UHRF1 in trophoblast regulation remains unknown. This is the first study to show that UHRF1 expression was localized in the cytoplasm of cytotrophoblasts, syncytiotrophoblasts, and villi columns, and decreased in the villi of patients with RPL. The invasion and cell viability in a UHRF1 knockdown trophoblast cell line were significantly decreased. In addition, the mRNA expression profiles of Swan71 cells were partially altered by UHRF1 knockdown. The altered immune-related genes were screened out and the pro-inflammatory TH1-type chemokine/cytokines CXCL2 and IL-1ß were identified as the most promising targets of UHRF1 in the trophoblasts, which were significantly increased in the UHRF1 knockdown Swan71 cells, villi, and serum from patients with RPL. The macrophages treated with the supernatants of UHRF1 knockdown Swan71 cells were polarized to the M1 phenotype and secreted high levels of pro-inflammatory cytokines, which might be driven by the activated MyD88/NF-κB signaling pathway and mediated by the increased expression of CXCR2 and IL-1R1 (CXCL2 and IL-1ß receptors, respectively). In addition, the supernatants of UHRF1 knockdown Swan71 cells showed stronger chemotaxis to macrophages than those from the controls. Our findings highlight the previously unknown roles of UHRF1 as one of the key regulators on the trophoblasts and their cross-talk with local immune cells, and demonstrate a potential approach for RPL intervention.

Outcome and risk prediction of early progression in patients with extranodal natural killer/T cell lymphoma from the CLCG study.

Recently, progression-free survival at 24 months (PFS24) was defined as clinically relevant for patients with extranodal NK/T cell lymphoma. Herein, the clinical data from two independent random cohorts (696 patients each in the primary and validation datasets) were used to develop and validate a risk index for PFS24 (PFS24-RI), and evaluate its ability to predict early progression. Patients achieving PFS24 had a 5-year overall survival (OS) of 95.8%, whereas OS was only 21.2% in those failing PFS24 (P<0.001). PFS24 was an important predictor of subsequent OS, independent of risk stratification. The proportion of patients achieving PFS24 and 5-year OS rates correlated linearly among risk-stratified groups. Based on multivariate analysis of the primary dataset, the PFS24-RI included five risk factors: stage II or III/IV, elevated lactate dehydrogenase, Eastern Cooperative Oncology Group score ≥2, primary tumor invasion, and extra-upper aerodigestive tract. PFS24-RI stratified the patients into low-risk (0), intermediate-risk (1-2), high-risk (≥3) groups with different prognoses. Harrell's C-index of PFS24-RI for PFS24 prediction was 0.667 in the validation dataset, indicating a good discriminative ability. PFS24-RI calibration indicated that the actual observed and predicted probability of failing PFS24 agreed well. PFS24-RI provided the probability of achieving PFS24 at an individual patient level.

The role of GATA switch in benzene metabolite hydroquinone inhibiting erythroid differentiation in K562 cells.

The phenolic metabolite of benzene, hydroquinone (HQ), has potential risks for hematological disorders and hematotoxicity in humans. Previous studies have revealed that reactive oxygen species, DNA methylation, and histone acetylation participate in benzene metabolites inhibiting erythroid differentiation in hemin-induced K562 cells. GATA1 and GATA2 are crucial erythroid-specific transcription factors that exhibit dynamic expression patterns during erythroid differentiation. We investigated the role of GATA factors in HQ-inhibited erythroid differentiation in K562 cells. When K562 cells were induced with 40 µM hemin for 0-120 h, the mRNA and protein levels of GATA1 and GATA2 changed dynamically. After exposure to 40 µM HQ for 72 h, K562 cells were induced with 40 µM hemin for 48 h. HQ considerably reduced the percentage of hemin-induced Hb-positive cells, decreased the GATA1 mRNA, protein, and occupancy levels at α-globin and ß-globin gene clusters, and increased the GATA2 mRNA and protein levels significantly. ChIP-seq analysis revealed that HQ reduced GATA1 occupancy, and increased GATA2 occupancy at most gene loci in hemin-induced K562 cells. And GATA1 and GATA2 might play essential roles in the erythroid differentiation protein interaction network. These results elucidate that HQ decreases GATA1 occupancy and increases GATA2 occupancy at the erythroid gene loci, thereby downregulating GATA1 and upregulating GATA2 expression, which in turn modulates the expression of erythroid genes and inhibits erythroid differentiation. This partially explains the mechanism of benzene hematotoxicity.

[Effect of Erxian Decoction-containing serum on H_2O_2-induced proliferation and osteogenic differentiation of MC3T3-E1 cells via BK channels].

This study aimed to investigate the effects of Erxian Decoction(EXD)-containing serum on the proliferation and osteogenic differentiation of MC3T3-E1 cells under oxidative stress through BK channels. The oxidative stress model was induced in MC3T3-E1 cells by H_2O_2, and 3 mmol·L~(-1) tetraethylammonium(TEA) chloride was used to block the BK channels in MC3T3-E1 cells. MC3T3-E1 cells were divided into a control group, a model group, an EXD group, a TEA group, and a TEA+EXD group. After MC3T3-E1 cells were treated with corresponding drugs for 2 days, 700 µmol·L~(-1) H_2O_2 was added for treatment for another 2 hours. CCK-8 assay was used to detect cell proliferation activity. The alkaline phosphatase(ALP) assay kit was used to detect the ALP activity of cells. Western blot and real-time fluorescence-based quantitative PCR(RT-qPCR) were used to detect protein and mRNA expression, respectively. Alizarin red staining was used to detect the mineralization area of osteoblasts. The results showed that compared with the control group, the model group showed significantly blunted cell proliferation activity and ALP activity, reduced expression of BK channel α subunit(BKα), collagen Ⅰ(COL1), bone morphogenetic protein 2(BMP2), osteoprotegerin(OPG), and phosphorylated Akt, decreased mRNA expression levels of Runt-related transcription factor 2(RUNX2), BMP2, and OPG, and declining area of calcium nodules. EXD-containing serum could significantly potentiate the cell proliferation activity and ALP activity, up-regulate the protein expression of BKα, COL1, BMP2, OPG, and phosphorylated Akt, and forkhead box protein O1(FoxO1), promote the mRNA expression of RUNX2, BMP2, and OPG, and enlarge the area of calcium nodules. However, BK channel blockage by TEA reversed the effects of EXD-containing serum in promoting the protein expression of BKα, COL1, BMP2, OPG, and phosphorylated Akt and FoxO1, increasing the mRNA expression of RUNX2, BMP2, and OPG, and enlarging the area of calcium nodules. EXD-containing serum could improve the proliferation activity, osteogenic differentiation, and mineralization ability of MC3T3-E1 cells under oxidative stress, which might be related to the regulation of BK channels and downstream Akt/FoxO1 signaling pathway.

The value of routine bone marrow examination in patients with extranodal NK/T-cell lymphoma staged with PET/CT.

BACKGROUND: Limited evidence supports the omission of routine bone marrow (BM) examination (biopsy and aspiration) in patients with nasal-type extranodal NK/T-cell lymphoma (ENKTCL). This study was aimed at assessing whether BM examination provides valuable information for positron emission tomography/computed tomography (PET/CT)-based staging in this patient population. PATIENTS AND METHODS: Patients newly diagnosed with ENKTCL who underwent initial staging with both PET/CT and BM examination between 2013 and 2020 were retrospectively identified in two Chinese institutions. Overall, 742 patients were included; the BM examination was positive in 67 patients. RESULTS: Compared with BM biopsy alone, the combination of BM biopsy and aspiration assessment did not afford any additional diagnostic value. No patient with a positive BM biopsy was found to have early-stage disease by PET/CT. BM biopsy or PET/CT led to upstaging from stage III to IV as a result of BM involvement in 21 patients. In 135 patients with distant organ involvement, BM involvement was associated with worse overall survival (OS) and progression-free survival (PFS) compared with the corresponding durations in patients without BM involvement (2-year OS: 35.9% vs. 60.4%, p < .001; PFS: 26% vs. 40.7%, p = .003). No difference in survival was noted between groups judged positive based on PET/CT and BM biopsy. CONCLUSION: Compared with aspiration, BM biopsy led to the detection of more BM lesions. Baseline PET/CT can be safely used to exclude BM involvement in early-stage disease. Overall, routine BM examination affords diagnostic or prognostic value over PET/CT in patients with advanced-stage nasal-type ENKTCL.

Proteomics-based evaluation of the mechanism underlying vascular injury via DNA interstrand crosslinks, glutathione perturbation, mitogen-activated protein kinase, and Wnt and ErbB signaling pathways induced by crotonaldehyde.

Crotonaldehyde (CRA)-one of the major environmental pollutants from tobacco smoke and industrial pollution-is associated with vascular injury (VI). We used proteomics to systematically characterize the presently unclear molecular mechanism of VI and to identify new related targets or signaling pathways after exposure to CRA. Cell survival assays were used to assess DNA damage, whereas oxidative stress was determined using colorimetric assays and by quantitative fluorescence study; additionally, cyclooxygenase-2, mitogen-activated protein kinase pathways, Wnt3a, ß-catenin, phospho-ErbB2, and phospho-ErbB4 were assessed using ELISA. Proteins were quantitated via tandem mass tag-based liquid chromatography-mass spectrometry and bioinformatics analyses, and 34 differentially expressed proteins were confirmed using parallel reaction monitoring, which were defined as new indicators related to the mechanism underlying DNA damage; glutathione perturbation; mitogen-activated protein kinase; and the Wnt and ErbB signaling pathways in VI based on Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and protein-protein interaction network analyses. Parallel reaction monitoring confirmed significant (p < 0.05) upregulation (> 1.5-fold change) of 23 proteins and downregulation (< 0.667-fold change) of 11. The mechanisms of DNA interstrand crosslinks; glutathione perturbation; mitogen-activated protein kinase; cyclooxygenase-2; and the Wnt and ErbB signaling pathways may contribute to VI through their roles in DNA damage, oxidative stress, inflammation, vascular dysfunction, endothelial dysfunction, vascular remodeling, coagulation cascade, and the newly determined signaling pathways. Moreover, the Wnt and ErbB signaling pathways were identified as new disease pathways involved in VI. Taken together, the elucidated underlying mechanisms may help broaden existing understanding of the molecular mechanisms of VI induced by CRA.

Spatiotemporal variation in residential PM2.5 and PM10 concentrations in China: National on-site survey.

BACKGROUND: Significant efforts have been directed toward addressing the adverse health effects of particulate matter, while few data exist to evaluate indoor exposure nationwide in China. OBJECTIVES: This study aimed to investigate dwellings particulate matter levels in the twelve cities in China and provide large data support for policymakers to accelerate the legislative process. METHODS: The current study was based on the CIEHS 2018 study and conducted in 12 cities of China. A total of 2128 air samples were collected from 610 residential households during the summer and winter. Both PM10 and PM2.5 were detected with a light-scattering dust meter in both the living room and bedroom. The Wilcoxon rank-sum test was performed to evaluate the correlations between PM2.5 and PM10 concentrations and both sampling season and site. Ratios of the living room to bedroom were calculated to evaluate the particulate matter variation between rooms. Hierarchical clustering was used to probe the question of whether the concentration varies between cities throughout China. RESULTS: The geometric means of the PM2.5 in living rooms and bedrooms were 39.80 and 36.55 µg/m3 in the summer, and 70.97 and 67.99 µg/m3 in the winter, respectively. In the summer, approximately 70 % of indoor dwelling PM2.5 exceeded the limit of 25 µg/m3, and for PM10 approximately 60 % of dwellings demonstrated levels higher than 50 µg/m3; the corresponding values were over 90 % and 80 % in winter, respectively. In Shijiazhuang, Lanzhou, Luoyang and Qingdao, the geometric means of the PM2.5 concentrations were observed to be 1.5 to 4.3 times higher during winter than during summer; similar concentrations in summer and winter were observed in Harbin, Wuxi, and Shenzhen, while the PM2.5 concentrations in Panjin were approximately 1.5 times higher in summer than in winter. There was no significant difference in particulate matter concentrations between the living rooms and bedrooms. Scatter plots showed that cities with low GDP and a small population had higher concentrations, while Shenzhen, which has a higher GDP and a large permanent population, had a relatively low concentration of particulate matter. CONCLUSIONS: Our results suggest that indoor air pollution is a severe problem in China. It is necessary to continue monitoring indoor air quality to observe the changing trend under the tremendous effort of the Chinese government.

Characterization and exposure assessment of household fine particulate matter pollution in China.

Household fine particulate matter (PM2.5 ) pollution greatly impacts residents' health. To explore the current national situation of household PM2.5 pollution in China, a study was conducted based on literature published from 1998 to 2018. After extracting data from the literature in conformity with the requirements, the nationwide household-weighted mean concentration of household PM2.5 (HPL) was calculated. Subgroup analyses of spatial, geographic, and temporal differences were also done. The estimated overall HPL in China was 132.2 ± 117.7 µg/m3 . HPL in the rural area (164.3 ± 104.5 µg/m3 ) was higher than that in the urban area (123.9 ± 122.3 µg/m3 ). For HPLs of indoor sampling sites, the kitchen was the highest, followed by the bedroom and living room. There were significant differences of geographic distributions. The HPLs in the South were higher than the North in four seasons. The inhaled dose of household PM2.5 among school-age children differed from provinces with the highest dose up to 5.9 µg/(kg·d). Countermeasures should be carried out to reduce indoor pollution and safeguard health urgently.

Pre-fenestration endovascular repair of aortic diseases in patients with zone 2 segment: A single-center experience.

OBJECTIVE: The present study aims to analyze the outcomes of three cases of pre-fenestration and branch stent-graft endovascular repair of aortic disease with zone 2 aortic lesions. METHODS: From August 2017 to June 2018, three patients with zone 2 aortic lesions underwent thoracic endovascular repair with innominate artery, left common carotid artery, and left subclavian artery recannulation using pre-fenestration and branched stent-grafts to preserve the patency of the aortic arch branches. RESULTS: The technical success rate was 100%. One patient had a proximal type I endoleak with no need for additional treatment. The overall mortality was 0%. All branches were patent. The follow-up period lasted for 2-15 months, with one patient lost to follow-up. There were no conversions to open surgical repair, aortic rupture, paraplegia, or retrograde type A aortic dissection. CONCLUSION: The use of a pre-fenestration and branch stent-graft for the thoracic endovascular repair of zone 2 aortic lesions is a feasible and effective method for aortic arch branch revascularization. The risk of this surgical procedure is high, requiring significant expertise. The procedure should be conducted only in experienced centers. Durability concerns should be assessed in future studies with long-term follow-up.

Selenium level does not differ in blood but increased in cerebrospinal fluid in Parkinson's disease: a meta-analysis.

Objective: Recent studies have found that selenium (Se) levels were associated with the risk of Parkinson's disease (PD), but the results were contradictory. Therefore, this meta-analysis was conducted to investigate the correlation between Se levels and PD.Methods: PubMed, Embase and Web of Science were searched published up to 28 October 2019. The differences between groups were analyzed by forest plots and results were pooled and assessed using a random-effect model. Standardized mean difference (SMD) and 95% confidence interval (CI) were used to assess the association between Se levels and the risk of PD. Subgroup analysis, meta-regression, and sensitivity analysis were also conducted. Publication bias was estimated using Begg's regression asymmetry test.Results: Finally, 12 articles involving 601 PD patients and 749 controls were included in this meta-analysis. The meta-analysis revealed a significantly higher cerebrospinal fluid (CSF) Se level in PD patients than those in controls (SMD = 1.22; 95%CI [0.05, 2.39]; p = 0.000). No publication bias was found.Conclusion: The meta-analysis indicated that CSF Se levels in PD patients were significantly higher than those in controls.

Nomogram predicting survival as a selection criterion for postmastectomy radiotherapy in patients with T1 to T2 breast cancer with 1 to 3 positive lymph nodes.

BACKGROUND: The role of postmastectomy radiotherapy (PMRT) in women with pT1-T2N1 breast cancer is controversial. The authors developed a nomogram that was predictive for overall survival (OS) and identified patients who derived no benefit from PMRT. METHODS: The authors retrospectively evaluated 4869 patients with pT1-T2N1 breast cancer who were treated with mastectomy between 2000 and 2014 in 11 Chinese hospitals. Rates of locoregional recurrence and distant metastasis were calculated using competing risk analysis, and disease-free survival and OS rates were calculated using the Kaplan-Meier method. Based on the risk factors identified from Cox regression analysis in 3298 unirradiated patients, a nomogram predicting OS was developed. The benefit of PMRT was evaluated in different risk groups stratified by the nomogram model. RESULTS: After a median follow-up of 65.9 months, the 5-year OS, disease-free survival, locoregional recurrence, and distant metastasis rates were 93.3%, 84.3%, 5.2%, and 8.3%, respectively. A total of 1571 patients (32.3%) underwent PMRT. On multivariable analyses, PMRT was found to increase OS significantly (hazard ratio, 0.61; P = .002). An OS prediction nomogram evaluated the effect of age; tumor location; tumor size; positive lymph node ratio; estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status; and treatment with trastuzumab. Based on nomogram scores, the entire patient cohort was classified into 3 risk groups. PMRT significantly improved the OS of patients in the intermediate-risk (P < .001) and high-risk groups (P = .004), but not in the low-risk group (P = .728). CONCLUSIONS: The authors developed a nomogram that is predictive of OS among women with pT1-T2N1 breast cancer after mastectomy. This nomogram may help to select a subgroup of patients with a good prognosis who will not benefit from PMRT.

Manure Application Did Not Enrich Antibiotic Resistance Genes in Root Endophytic Bacterial Microbiota of Cherry Radish Plants.

Growing evidence suggests that livestock manure used as organic fertilizer in agriculture may lead to the potential propagation of antibiotic resistance genes (ARGs) from "farm to fork." However, little is known about the impacts of manure fertilization on the incidence of ARGs in the plant-associated microbiomes (including rhizosphere, endosphere, and phyllosphere), which hampers our ability to assess the dissemination of antibiotic resistance in the soil-plant system. Here, we constructed a pot experiment to explore the effects of poultry and cattle manure applications on the shifts in the resistome in the plant microbiome of harvested cherry radish. A total of 144 ARGs conferring resistance to eight major classes of antibiotics were detected among all the samples. Rhizosphere and phyllosphere microbiomes harbored significantly higher diversity and abundance of ARGs than did root endophytic microbiomes of cherry radish. Manure application significantly increased the abundance of ARGs in the rhizosphere and phyllosphere but not in the endophytes of the root, which is the edible part of cherry radish. Soil and plant microbiomes changed dramatically after manure applications and clustered separately according to different sample types and treatments. Structural equation modeling revealed that bacterial abundance was the most important factor modulating the distribution patterns of soil and plant resistomes after accounting for multiple drivers. Taken together, we provide evidence that enrichment of the resistome in the rhizosphere and phyllosphere of cherry radish is more obvious than with the endosphere after manure application, suggesting that manure amendment might not enhance the dissemination of ARGs into the root of vegetables in the pot experiment.IMPORTANCE Our study provides important evidence that manure application increased the occurrence of ARGs in the rhizosphere and phyllosphere of cherry radish, compared with that in the endophytic bacterial microbiota of root, which is the edible part of cherry radish. Our findings suggest that although manure amendment is a significant route of ARGs entering agricultural soils, these manure-derived ARGs may be at low risk of migrating into the endophytes of root vegetables.

Radiotherapy plays an important role in improving the survival outcome in patients with T1-2N1M0 breast cancer - a joint analysis of 4262 real world cases from two institutions.

BACKGROUND: To compare the survival outcomes between breast-conserving surgery (BCS) and modified radical mastectomy (MRM), and to investigate the role of radiotherapy (RT) in patients with pT1-2N1M0 breast cancer. METHODS: A total of 4262 women with T1-2N1M0 breast cancer treated at two institutions were retrospectively reviewed. A total of 3858 patients underwent MRM, and 832 (21.6%) of them received postoperative RT (MRM + RT). A total of 404 patients received BCS plus postoperative RT (BCS + RT). All patients received axillary lymph node dissection, while 3.8% of them had upfront sentinel node biopsy. The association of survival outcomes with different surgical modalities (BCS vs. MRM) and the role of RT were evaluated using multivariable proportional hazards regression and confirmed by the propensity score-matching (PSM) method. RESULTS: At a median follow-up of 71 months (range of 6-230 months), the 5-year overall survival (OS) rates of the BCS and MRM groups were 96.5 and 92.7%, respectively (P = .001), and the corresponding 5-year disease-free-survival (DFS) and locoregional recurrence (LRR) rates were 92.9 and 84.0%, and 2.0 and 7.0% (P = .001), respectively (P < .001). Multivariate analysis revealed that RT was an independent prognostic factor for improved OS (P = .001) and DFS (P = .009), and decreased LRR (P < .001). However, surgery procedure was not independently associated with either OS (P = .495), DFS (P = .204), or LRR (P = .996), which was confirmed by PSM analysis. CONCLUSION: Postoperative radiotherapy rather than the surgery procedures was associated with superior survival outcomes in patients with T1-2N1M0 breast cancer.

Risk-based, response-adapted therapy for early-stage extranodal nasal-type NK/T-cell lymphoma in the modern chemotherapy era: A China Lymphoma Collaborative Group study.

We aimed to determine the survival benefits of chemotherapy (CT) added to radiotherapy (RT) in different risk groups of patients with early-stage extranodal nasal-type NK/T-cell lymphoma (ENKTCL), and to investigate the risk of postponing RT based on induction CT responses. A total of 1360 patients who received RT with or without new-regimen CT from 20 institutions were retrospectively reviewed. The patients had received RT alone, RT followed by CT (RT + CT), or CT followed by RT (CT + RT). The patients were stratified into different risk groups using the nomogram-revised risk index (NRI). A comparative study was performed using propensity score-matched (PSM) analysis. Adding new-regimen CT to RT (vs RT alone) significantly improved overall survival (OS, 73.2% vs 60.9%, P < .001) and progression-free survival (PFS, 63.5% vs 54.2%, P < .001) for intermediate-risk/high-risk patients, but not for low-risk patients. For intermediate-risk/high-risk patients, RT + CT and CT + RT resulted in non-significantly different OS (77.7% vs 72.4%; P = .290) and PFS (67.1% vs 63.1%; P = .592). For patients with complete response (CR) after induction CT, initiation of RT within or beyond three cycles of CT resulted in similar OS (78.2% vs 81.7%, P = .915) and PFS (68.2% vs 69.9%, P = .519). For patients without CR, early RT resulted in better PFS (63.4% vs 47.6%, P = .019) than late RT. Risk-based, response-adapted therapy involving early RT combined with CT is a viable, effective strategy for intermediate-risk/high-risk early-stage patients with ENKTCL in the modern treatment era.

The predictive value of procalcitonin in ventilator-associated pneumonia after cardiac valve replacement.

This study aimed to evaluate the predictive value of procalcitonin (PCT) in ventilator-associated pneumonia (VAP) after cardiac valve replacement. A total of 80 patients who underwent cardiac valve replacement in our department were enrolled in this study. Of these patients,40 were diagnosed with VAP and assigned to the observation group, while the other 40 patients not diagnosed with VAP were assigned to the control group. The changes in serum PCT, white blood cell count and C-reactive protein (CRP) were observed before each operation (T0), on the first day after the operation (T1), the second day after the operation (T2) and the third day after the operation (T3). After the operation, the serum PCT in the observation group was significantly higher than those at different time points after the operation, and also significantly higher than those in the control group (p < .05). In the control group, PCT was significantly higher after the operation than before the operation (p < .05), but the differences among the different postoperative time points were not statistically significant (p > .05). In the two groups, the white blood cell count and CRP were significantly higher after the operation than before the operation (p < .05), but the differences between the two groups were not statistically significant (p > .05). Serum PCT is an early, sensitive and highly specific high-risk monitoring index and has an early prediction value for VAP after cardiac valve replacement.

Diversity of herbaceous plants and bacterial communities regulates soil resistome across forest biomes.

Antibiotic resistance is ancient and prevalent in natural ecosystems and evolved long before the utilization of synthetic antibiotics started, but factors influencing the large-scale distribution patterns of natural antibiotic resistance genes (ARGs) remain largely unknown. Here, a large-scale investigation over 4000 km was performed to profile soil ARGs, plant communities and bacterial communities from 300 quadrats across five forest biomes with minimal human impact. We detected diverse and abundant ARGs in forests, including over 160 genes conferring resistance to eight major categories of antibiotics. The diversity of ARGs was strongly and positively correlated with the diversity of bacteria, herbaceous plants and mobile genetic elements (MGEs). The ARG composition was strongly correlated with the taxonomic structure of bacteria and herbs. Consistent with this strong correlation, structural equation modelling demonstrated that the positive effects of bacterial and herb communities on ARG patterns were maintained even when simultaneously accounting for multiple drivers (climate, spatial predictors and edaphic factors). These findings suggest a paradigm that the interactions between aboveground and belowground communities shape the large-scale distribution of soil resistomes, providing new knowledge for tackling the emerging environmental antibiotic resistance.

Persistent peripheral blood EBV-DNA positive with high expression of PD-L1 and upregulation of CD4 + CD25 + T cell ratio in early stage NK/T cell lymphoma patients may predict worse outcome.

Although gemcitabine, oxaliplatin and L-asparaginase/pegylated asparaginase (P-GEMOX) treatment for early-stage extranodal natural killer/T cell lymphoma (ENKTL) is effective, some patients die within 1 year of diagnosis. We attempted to determine an optimal biomarker for identifying such patients. We enrolled 71 patients with ENKTL who received P-GEMOX between January 2011 and January 2014. We classified the patients according to the outcome into worse (died within 1 year) or better groups (survival time ≥ 3, 4 or 5 years). The area under the curve (AUC) was determined to identify the optimal biomarker for differentiating the groups. The AUC was highest in patients who were plasma Epstein-Barr virus (EBV) DNA-positive post-treatment. The AUC was 0.82, 0.86 and 0.86 when the worse group was compared to the better group, respectively. Among the post-treatment EBV DNA-positive patients, as compared to EBV DNA-negative patients, pre-treatment EBV DNA-positive patients had a higher proportion of CD4 + CD25 + T cells. There was higher programmed cell death protein ligand-1(PD-L1) expression in post-treatment EBV DNA-positive patients. Post-treatment positive EBV DNA status maybe a useful biomarker of worse outcomes in early stage ENKTL.

Ultrastructure of Female Antennal Sensilla of an Endoparasitoid Wasp, Quadrastichus mendeli Kim & La Salle (Hymenoptera: Eulophidae: Tetrastichinae).

The antennal sensilla of female Quadrastichus mendeli Kim & La Salle (Hymenoptera: Eulophidae: Tetrastichinae) were observed with scanning and transmission electron microscopy in this study. The antenna of Q. mendeli was geniculate, and the flagellum was composed of seven subsegments. Six distinct types of sensory receptors were observed, including sensilla basiconic capitate peg, sensilla böhm, sensilla chaetica, sensilla campaniformia, sensilla placodea and sensilla trichodea. Sensilla basiconic capitate pegs were found on the flagellomeres, and Böhm sensilla were found on the basal part of scape and the pedicel. Two morphological subtypes of sensilla chaetica were found on the antennae, and sensilla campaniformia were only found on the pedicel. Sensilla placodea were divided into two morphological subtypes that were found on the flagellomeres. Sensilla trichodea were found on the 2nd-6th flagellomere. By comparison to existing antennal sensilla, it was found that sensilla basiconic capitate peg, sensilla chaetica, sensilla placodea and sensilla trichodea were the most common sensilla of the parasitoids of Eulophidae. The external and internal morphology, types, number, distribution, length, and width of these sensilla were described, and their possible functions are discussed in conjunction with the host-detection behavior. Future studies on the host location mechanisms in Q. mendeli will be facilitated by these observations.