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This study aimed to evaluate arsenic (As), cadmium (Cd), chromium (Cr), and lead (Pb) levels in dried chili peppers from nine districts in Guizhou Province. These heavy metals, widely dispersed and capable of transferring to crops, pose potential health risks to humans. The assessment included modeling daily intake (EDI), target hazard quotient (THQ), total target hazard index (TTHQ), and target carcinogenic risk (TCR) to assess health risks across different population groups. Results showed chromium (0.9540 ± 0.301 mg/kg) and lead (0.8949 ± 0.266 mg/kg) had the highest concentrations, followed by arsenic (0.3287 ± 0.093 mg/kg) and cadmium (0.0627 ± 0.017 mg/kg). Children exhibited higher EDI values than adults, indicating greater health risks from dried chili pepper consumption at equivalent levels. THQ and TTHQ values were below 1 across all regions, indicating no significant health risks associated with dried chili pepper consumption. Similarly, TCR values were below 10-4 for all nine regions, indicating an acceptable level of carcinogenic risk. Overall, consuming dried chili peppers in Guizhou Province poses an acceptable health risk, but caution is advised, especially for children, to limit heavy metal exposure., (© 2024. The Author(s).)

This work was to investigate the effect of four prebiotic saccharides gum arabic (GA), fructooligosaccharide (FOS), konjac glucomannan (KGM), and inulin (INU) incorporation on the encapsulation efficiency (EE), physicochemical stability, and in vitro digestion of urolithin A-loaded liposomes (UroA-LPs). The regulation of liposomes on gut microbiota was also investigated by in vitro colonic fermentation. Results indicated that liposomes coated with GA showed the best EE, bioaccessibility, storage and thermal stability, the bioaccessibility was 1.67 times of that of UroA-LPs. The UroA-LPs coated with FOS showed the best freeze-thaw stability and transformation. Meanwhile, saccharides addition remarkably improved the relative abundance of Bacteroidota, reduced the abundances of Proteobacteria and Actinobacteria. The UroA-LPs coated with FOS, INU, and GA exhibited the highest beneficial bacteria abundance of Parabacteroides, Monoglobus, and Phascolarctobacterium, respectively. FOS could also decrease the abundance of harmful bacteria Collinsella and Enterococcus, and increase the levels of acetic acid, butyric acid and iso-butyric acid. Consequently, prebiotic saccharides can improve the EE, physicochemical stability, gut microbiota regulation of UroA-LPs, and promote the bioaccessibility of UroA, but the efficiency varied based on saccharides types, which can lay a foundation for the application of UroA in foods industry and for the enhancement of its bio-activities., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: Precise determination of cervical lymph node metastasis (CLNM) involvement in patients with early-stage thyroid cancer is fairly significant for identifying appropriate cervical treatment options. However, it is almost impossible to directly judge lymph node metastasis based on the imaging information of early-stage thyroid cancer patients with clinically negative lymph nodes., Methods: Preoperative US images (BMUS and CDFI) of 1031 clinically node negative PTC patients definitively diagnosed on pathology from two independent hospitals were divided into training set, validation set, internal test set, and external test set. An ensemble deep learning model based on ResNet-50 was built integrating clinical variables, BMUS, and CDFI images using a bagging classifier to predict metastasis of CLN. The final ensemble model performance was compared with expert interpretation., Results: The ensemble deep convolutional neural network (DCNN) achieved high performance in predicting CLNM in the test sets examined, with area under the curve values of 0.86 (95% CI 0.78-0.94) for the internal test set and 0.77 (95% CI 0.68-0.87) for the external test set. Compared to all radiologists averaged, the ensemble DCNN model also exhibited improved performance in making predictions. For the external validation set, accuracy was 0.72 versus 0.59 (p = 0.074), sensitivity was 0.75 versus 0.58 (p = 0.039), and specificity was 0.69 versus 0.60 (p = 0.078)., Conclusions: Deep learning can non-invasive predict CLNM for clinically node-negative PTC using conventional US imaging of thyroid cancer nodules and clinical variables in a multi-institutional dataset with superior accuracy, sensitivity, and specificity comparable to experts., Critical Relevance Statement: Deep learning efficiently predicts CLNM for clinically node-negative PTC based on US images and clinical variables in an advantageous manner., Key Points: • A deep learning-based ensemble algorithm for predicting CLNM in PTC was developed. • Ultrasound AI analysis combined with clinical data has advantages in predicting CLNM. • Compared to all experts averaged, the DCNN model achieved higher test performance., (© 2023. The Author(s).)

Cancer stem cells (CSCs), a rare subset of tumor cells, have been recognized as promotive role on tumor initiation and propagation. Among, aerobic glycolysis, widely clarified in multiple tumor cells, is the key for maintaining cancer stemness. Regrettably, it is largely unknown about the connection of cellular metabolic reprogramming and stemness in gastric carcinoma (GC). Two GC parental cells lines PAMC-82 and SNU-16 and their spheroids were obtained to determine the expression status of POU1F1 using quantitative real-time PCR (qRT-PCR) and western blotting analysis, respectively. Gain or loss-of-function assay was employed to assess its biological effects. Sphere formation and transwell assays were performed to evaluate the stem cell-like traits, including self-renewal capacity, migration and invasion. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were conducted for determining the binding relationship of POU1F1 on ENO1 promoter region. Herein, aberrantly upregulated POU1F1 was observed in spheroids, compared with the parental PAMC-82 and SNU-16 cells, which promoted stem cell-like traits, as representing increasing sphere formation, enhanced cell migration and invasion. Additionally, POU1F1 expression was positively with glycolytic signaling, as displaying increasing glucose consumption, lactic acid production, and extracellular acid ratio (ECAR). Furthermore, POU1F1 was identified to be a transcriptional activator of ENO1, of which overexpression remarkably abolished POU1F1 knockdown-mediated blocking effects. Taken together, we draw a conclusion that POU1F1 facilitated the stem cell-like properties of GC cells through transcriptionally augmenting ENO1 to enhance glycolysis., (© 2023 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Objective: Due to the rarity of angioimmunoblastic T-cell lymphoma (AITL), very limited data concerning its incidence patterns and prognostic factors are available. This study aimed to explore the incidence, characteristics, survival outcomes, and prognostic factors of AITL., Methods: Age-adjusted incidence and temporal trends were calculated based on 1247 AITL patients from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER)-13 database. A total of 1525 AITL patients from the SEER-18 database and 43 patients from our single center were included for survival analysis and nomogram construction., Results: The age-adjusted incidence for overall cohort was 0.123 [95% confidence interval (CI), 0.117-0.131) per 100 000 during 1992-2017. The overall incidence increased steeply at the rate of 15.3% (95%CI 11.0%-19.8%, P<0.001) per year during 1992-2004, but remained stable during 2004-2017 (P=0.200). Similar incidence trends were observed in age, sex, and stage subgroups. The final nomograms consisted of four variables: age at diagnosis, sex, Ann Arbor stage, and primary site. The concordance index (C-index) of the nomogram for 5-year overall survival prediction was 0.717, 0.690 and 0.820 in the training cohort, validation cohort-1 and cohort-2, respectively. Regarding the disease-specific survival (DSS), the nomogram also demonstrated a good discrimination level, with the C-index for predicting the probability of DSS at 5 years of 0.716, 0.682 and 0.813 for the three cohorts, respectively. The calibration displayed good concordance between the nomogram-predicted and actual observed outcomes., Conclusion: The age-adjusted incidence for AITL was low during 1992-2017. The incidence continuously increased during 1992-2004, but remained stable during 2004-2017. The nomograms as proposed may provide a favorable and accurate prognostic survival prediction in AITL., (© 2022. Huazhong University of Science and Technology.)

(1) Background: Afatinib has been approved for patients with non-small cell lung cancer (NSCLC) carrying major uncommon epidermal growth factor receptor gene ( EGFR ) mutations. Dacomitinib, another second-generation tyrosine kinase inhibitor, has also shown promising potential for uncommon EGFR mutations. However, no comparative study has been conducted. (2) Methods: Two cohorts were employed: the AFANDA cohort, an ambispective cohort including 121 patients with uncommon EGFR mutations admitted to two tertiary hospitals in China, and an external validation afatinib cohort (ex-AC), extracted from the Afatinib Uncommon EGFR Mutations Database (N = 1140). The AFANDA cohort was divided into an afatinib cohort (AC) and a dacomitinib cohort (DC) for internal exploration. Objective response rate (ORR), progression-free survival (PFS), and adverse events (AEs) were assessed for comparison. Progression patterns and resistance mechanisms were explored. (3) Results: In total, 286 patients with advanced NSCLC carrying uncommon EGFR mutations treated with afatinib or dacomitinib were enrolled, including 79 in the AFANDA cohort (44 in the DC, 35 in the AC) and 207 in the ex-AC. In internal exploration, the ORR of the DC was significantly higher than that of the AC (60.5 vs. 26.7%, p = 0.008), but there was no significant difference in median PFS between the DC and the AC (12.0 months vs. 10.0 months, p = 0.305). Multivariate analysis confirmed an independent favorable effect of dacomitinib on PFS (hazard ratio (HR), 1.909; p = 0.047). In external validation, multivariate analysis confirmed the independent prognostic role of dacomitinib in PFS (HR, 1.953; p = 0.029). Propensity score matching analysis confirmed the superiority of dacomitinib over afatinib in terms of PFS in both univariate and multivariate analyses. Toxicity profiling analysis suggested more G1 ( p = 0.006), but fewer G3 ( p = 0.036) AEs in the DC than in the AC. Progression patterns revealed that the incidence of intracranial progression in the AC was significantly higher than that in the DC (50 vs. 21.1%, p = 0.002). Drug resistance analysis indicated no significant difference in the occurrence of T790M between the AC and the DC (11.8 vs. 15.4%, p = 0.772). (4) Conclusions: Compared with afatinib, dacomitinib demonstrated a more favorable activity with manageable toxicity and different progression patterns in patients with NSCLC carrying uncommon EGFR mutations.

Objective: Dacomitinib has been approved for non-small-cell lung cancer (NSCLC) patients harboring classical epidermal growth factor receptor ( EGFR ) mutations; however, clinical evidence of its activity on major uncommon EGFR mutations is currently limited. Materials and methods: This was a dual-center, single-arm, ambispective cohort study in China. Patients with histologically confirmed metastatic or recurrent NSCLC harboring major uncommon EGFR mutations were eligible for the study. The objective response rate and disease control rate were determined by RECIST 1.1 every 1-2 months. Adverse events were assessed by CTCAE 5.0. Results: In total, 32 NSCLC patients were enrolled between July 2020 and January 2022, and 18 (56.3%) patients received dacomitinib as first-line therapy. Median age was 64 years, and 20 (62.5%) were female. The mutations identified were G719X ( n = 24; 75%), followed by L861X ( n = 10; 31.3%), and S768I ( n = 8; 25%). In the first-line setting, 72.2% of patients (13/18) had a confirmed partial response and 100% (18/18) had disease control, and the median progression-free survival (PFS) and overall survival (OS) were unreached. In the whole cohort, 56.3% of patients (18/32) had a confirmed partial response and 90.6% (29/32) had disease control, and the median PFS was 10.3 months (95% confidence interval, 6.1-14.5) and the median OS was 36.5 months. Except for one case not available for brain re-evaluation, control of the intracranial metastases was observed in 13 patients (13/14, 92.9%). No grade 4-5 adverse events (AEs) occurred, but all patients had grade 1-2 AEs, and 12.5% (4/32) patients required a dosage reduction due to intolerable AEs. Conclusions: Dacomitinib demonstrated favorable activity with manageable toxicity in patients with NSCLC harboring major uncommon EGFR mutations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Yang, Cai, Li, Xu, Zhang, Zhou, Wang, Wang, Hu, Yan and Wang.)

Dilated cardiomyopathy (DCM) is a primary myocardial disease of unclear mechanism and poor prevention. The purpose of this study is to explore the potential molecular mechanisms and targets of DCM via bioinformatics methods and try to diagnose and prevent disease progression early. We screened 333 genes differentially expressed between DCM and normal heart samples from GSE141910, and further used Weighted correlation network analysis to identify 197 DCM-related genes. By identifying the key modules in the protein-protein interaction network and Least Absolute Shrinkage and Selection Operator regression analysis, seven hub DCM genes (CX3CR1, AGTR2, ADORA3, CXCL10, CXCL11, CXCL9, SAA1) were identified. Calculating the area under the receiver's operating curve revealed that these 7 genes have an excellent ability to diagnose and predict DCM. Based on this, we built a logistic regression model and drew a nomogram. The calibration curve showed that the actual incidence is basically the same as the predicted incidence; while the C-index values of the nomogram and the four external validation data sets are 0.95, 0.90, 0.96, and 0.737, respectively, showing excellent diagnostic and predictive ability; while the decision curve indicated the wide applicability of the nomogram is helpful for clinicians to make accurate decisions., (© 2022. The Author(s).)

Background: Dacomitinib is a first-line treatment for patients with non-small cell lung cancer (NSCLC) harboring common epidermal growth factor receptor ( EGFR ) mutations; however, clinical evidence of its activity on NSCLC with complex EGFR mutations is limited., Methods: Patients harboring complex (common mutations co-existing with uncommon mutations), or common (comparison cohort) EGFR mutations, who were treated with dacomitinib, were retrospectively evaluated in the Chinese National Cancer Center and the China PLA hospital between August 2019 and August 2021., Results: In total, 72 patients with NSCLC harboring complex (C+U group, n=18) or common (C group, n=54) EGFR mutations and being treated with dacomitinib were enrolled. In the C+U group, 16 cases (88.9%) harbored L858R mutations co-existing with uncommon mutations located from exon 18 to exon 25 of EGFR (mostly E709X), and two cases harbored exon 19 deletion co-existing with G724S or K754E. Among the 15 evaluable patients, the objective response rate (ORR) was 40% (6/15), and the disease control rate (DCR) was 73.3% (11/15). The median progression-free survival (PFS) was 7.5 months [95% confidence interval (CI), 4.4-10.6 months]. Except for the application line of dacomitinib (P=0.039), no significant statistical differences were found in other characteristics and adverse events between the two groups. The Kaplan-Meier method revealed no significant differences in PFS (P=0.889) and overall survival (OS) (P=0.703). However, the stratified analysis found worse PFS in the C+U group than that observed in the C group when receiving 1 st and ≥3 rd line dacomitinib treatment, while its OS was worse than that of group C when receiving ≥3 rd line treatment. Furthermore, in a multivariate analysis, complex mutation status was an independent prognostic factor for OS (P = 0.038) in the entire cohort., Conclusions: This study indicated a worse response and prognosis of patients with NSCLC harboring complex EGFR mutations than those harboring common EGFR mutations when treated with dacomitinib. Further studies and data are needed to confirm this conclusion., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-21-1841/coif). The authors have no conflicts of interest to declare., (2022 Journal of Thoracic Disease. All rights reserved.)

Seven new acylated C-glycosylflavones, oreocharioside A-G, together with two known compounds were isolated from the whole plant of Oreocharis auricula. Their structures were characterized by the comprehensive analysis of their NMR, IR, UV, CD spectra and HRESIMS data. All the new compounds were evaluated for the antioxidant and anti-inflammatory activities. The results showed that compounds 1 and 2 had significant DPPH and ABTS radical scavenging activities, with the IC 50 values of 0.32-3.20 μg/mL. Compounds 2 and 3 exhibited the higher potency among all the new compounds in reducing TNF-α production., (Copyright © 2022 Elsevier B.V. All rights reserved.)

This study explores the role of the long noncoding RNA (LncRNA) CRNDE in cisplatin (CDDP) resistance of gastric cancer (GC) cells. Here, we show that LncRNA CRNDE is upregulated in carcinoma tissues and tumor-associated macrophages (TAMs) of GC patients. In vitro experiments show that CRNDE is enriched in M2-polarized macrophage-derived exosomes (M2-exo) and is transferred from M2 macrophages to GC cells via exosomes. Silencing CRNDE in M2-exo reverses the promotional effect of M2-exo on cell proliferation in CDDP-treated GC cells and homograft tumor growth in CDDP-treated nude mice. Mechanistically, CRNDE facilitates neural precursor cell expressed developmentally downregulated protein 4-1 (NEDD4-1)-mediated phosphatase and tensin homolog (PTEN) ubiquitination. Silencing CRNDE in M2-exo enhances the CDDP sensitivity of GC cells treated with M2-exo, which is reduced by PTEN knockdown. Collectively, these data reveal a vital role for CRNDE in CDDP resistance of GC cells and suggest that the upregulation of CRNDE in GC cells may be attributed to the transfer of TAM-derived exosomes., (© 2021 The Authors.)

Background: The occurrence of recurrence and metastasis after treatment is a major challenge in the treatment of gastric cancer. This study was based on the methionine (Met)-dependent characteristics of gastric cancer cells to explore the effect of Met deficiency on the occurrence and development of gastric cancer., Methods: Human gastric cancer cell lines MKN45 and AGS and nude mice model were used to explore how Met affects gastric cancer by regulating lncRNA PVT1., Results: The levels of lncRNA PVT1 in gastric cancer cells and human gastric cancer xenografts of nude mice were down-regulated under the condition of Met deficiency. The cell viability and cell proliferation were declined after MKN45 and SGC-790 cells were cultured in Met-deficient medium. LncRNA PVT1 could affect BNIP3 promoter DNA methylation level through its interaction with DNMT1. Moreover, the silence of lncRNA PVT1 and the up-regulation of BNIP3 level inhibited the gastric cancer cell proliferation. Met deficiency could up-regulate BNIP3 expression by inhibiting the binding of lncRNA PVT1 to DNMT1, and activate mitophagy, thus inhibiting gastric cancer cell proliferation., Conclusion: Our study suggested that Met deficiency could down-regulate the expression of lncRNA PVT1, further demethylated the promoter of BNIP3, thus inhibiting the proliferation of gastric cancer cells by activating mitophagy., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Gastric cancer (GC) derived exosomes (Exos) aggravate GC development by facilitating M2 macrophage polarization and long non-coding RNA (lncRNA) HCG18 was highly expressed in GC. This study aimed to investigate whether the exosomal lncRNA HCG18 regulated the M2 macrophage polarization in GC and the possible mechanism., Methods: The isolated GC cells (GCCs)-Exos were identified using transmission electron microscopy, Nanoparticle Tracking Analysis and Western blot. The GCCs-Exos function was verified by enzyme-linked immunosorbent assay and flow cytometry. Meanwhile, the exosomal lncRNA HCG18 function was determined using thein vitro assays. Furthermore, the underlying mechanism of the exosomal lncRNA HCG18 that regulated M2 macrophage polarization in GC was investigated using dual-luciferase reporter gene assay and RNA pull-down., Results: After the validation of GCCs-Exos, the GCCs-Exos facilitated the M2 macrophage polarization. The in vitro assays confirmed that the exosomal lncRNA HCG18 positively regulated the M2 macrophage polarization. Mechanistically, lncRNA HCG18 bound to miR-875-3p, miR-875-3p bound to KLF4. Furthermore, GCCs-exosomal lncRNA HCG18 elevated the KLF4 expression by decreasing miR-875-3p in macrophages to facilitate M2 macrophage polarization, thus alleviating GC. The in vivo assays clarified that the GCCs-exosomal lncRNA HCG18 restrained the tumor growth of GC induced by M2 macrophages., Conclusion: GCCs-exosomal lncRNA HCG18 elevated KLF4 expression by decreasing miR-875-3p in macrophages to facilitate the M2 macrophage polarization., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Transcription factors (TFs) play an important role in tumors. We integrated and analyzed 13 GPL570 platform gastric cancer (GC) microarrays, identified 10 independent prognostic TFs, and constructed a GC prognostic model. Using GSE26942 as the verification set, the Kaplan-Meier curve showed that the signature distinguish the survival rate of GC patients (P < 0.01), and the AUC values are 0.746 and 0.630, respectively. Compared with the clinicopathological characteristics, the signature is an independent prognostic factor (P < 0.05). A nomogram was established based on the model, and the five-year calibration curve verified that the prediction of the nomogram was almost consistent with the actual survival rate, C-index of 0.747 indicated a moderate prognostic ability. The analysis of target genes of 10 TFs showed that they are closely related to the progression of GC. External database and rt-PCR showed that the RNA and protein expression of TFs are consistent with our analysis., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background/aims: Targeted drug delivery vehicles with low immunogenicity and toxicity are needed for cancer therapy. Here, we prepare an active targeting drug carrier of low immunogenicity and toxicity for targeted therapy., Methods: Immature dendritic cells (imDCs) from BALB/c mice were used as donor cells of exosomes (Exos) that were transfected with the plasmids expressing fusion proteins of a tumor-targeting peptide known as internalizing RGD (iRGD) to construct a type of tumor-targeting iRGD-Exos and observe the interaction between these iRGD-Exos. Also, recombinant methioninase (rMETase) was loaded into the iRGD-Exos by electroporation to construct iRGD-Exos-rMETase and to assess the tumor-targeting function of the iRGD-Exos-rMETase. Finally, 30 BALB/c were randomly divided into five groups (n = 6), to observe tumor growth in vivo., Results: The iRGD-Exos-rMETase was 99.58 nm in diameter and presented a unique "goblet" structure under transmission electron microscopy (TEM), with the encapsulation efficiency (EE) of 19.05%. iRGD-Exos-rMETase group has the strongest tumor suppressive effect. Compared to the iRGD-Exos-rMETase group, rMETase group and the blank-Exos-rMETase group were less effective, while the PBS group and the iRGD-Exos group showed no inhibitory effect on tumor growth. After treatment, the iRGD-Exos-rMETase group had gastric tumors significantly smaller and lighter than the other groups (P < 0.05)., Conclusion: The iRGD-Exos-rMETase is an effective antitumor therapy that delivers rMETase to tumor tissue using the iRGD-Exos. With its favorable inhibitory effect and tumor-targeting function, the iRGD-Exos-rMETase shows excellent potential value and exciting prospects in clinical applications.

Serotonin (5-HT)-based antidepressants, selective serotonin reuptake inhibitors (SSRIs) aim to enhance serotonergic activity by blocking its reuptake. We propose PTEN as a target for an alternative approach for regulating 5-HT neuron activity in the brain and depressive behaviors. We show that PTEN is elevated in central 5-HT neurons in the raphe nucleus by chronic stress in mice, and selective deletion of Pten in the 5-HT neurons induces its structural plasticity shown by increases of dendritic branching and density of PSD95-positive puncta in the dendrites. 5-HT levels are elevated and electrical stimulation of raphe neurons evokes more 5-HT release in the brain of condition knockout (cKO) mice with Pten-deficient 5-HT neurons. In addition, the 5-HT neurons remain normal electrophysiological properties but have increased excitatory synaptic inputs. Single-cell RNA sequencing revealed gene transcript alterations that may underlay morphological and functional changes in Pten-deficient 5-HT neurons. Finally, Pten cKO mice and wild-type mice treated with systemic application of PTEN inhibitor display reduced depression-like behaviors. Thus, PTEN is an intrinsic regulator of 5-HT neuron activity, representing a novel therapeutic strategy for producing antidepressant action.

This study focused on the role of methionine (MET) in the autophagy of gastric cancer stem cells (GCSCs) and aims to elaborate its regulatory mechanism. In the present study, the GCSCs were isolated from human gastric cancer cell lines using an anti-CD44 antibody, and then cultured in MET + homocysteine (HCY) - or MET - HCY + medium. In MET + HCY - treated GCSCs, autophagy was suppressed, the methylation and phosphorylation of RAB37 were elevated, and miR-200b expression was down-regulated. Lentiviral vector (LV-) carrying methionine-γ lyase (an enzyme that could specifically lyse MET; Metase) promoted autophagy, reduced the methylation and phosphorylation of RAB37, and up-regulated miR-200b expression in MET + HCY - -treated GCSCs. Then, we found that miR-200b suppressed the expression of protein kinase C α (PKCα), a protein that could inactivate RAB37 through promoting its phosphorylation. LV-Metase down-regulated RAB37 phosphorylation via miR-200b/PKCα, thus promoting the RAB37-mediated autophagy and suppressing cell viability in MET + HCY - treated GCSCs. Finally, the in vivo study proved that LV-Metase treatment inhibited tumor growth through up-regulating RAB37 expression. In conclusion, MET suppressed RAB37 expression via enhancing its methylation and suppressed RAB37 activity via miR-200b/PKCα axis, thus repressing RAB37-mediated autophagy in GCSCs. The supplementation of Metase lysed MET, thus inducing the autophagy of GCSCs and inhibiting tumor growth.

Background: Gastric cancer is a common malignancy and had poor response to treatment due to its strong heterogeneity. This study aimed to identify essential genes associated with diffuse type gastric cancer and construct a powerful prognostic model., Results: We conducted a weighted gene co-expression network analysis (WGCN) using transcripts per million (TPM) expression data from The Cancer Genome Atlas (TCGA) to find out the module related with diffuse type gastric cancer. Combining Least Absolute Shrinkage and Selection Operator (LASSO) with multi-cox regression, the 10 specific genes risk score model of diffuse type gastric cancer was established. The concordance index (0.97), the area under the respective ROC curves (AUCs) (1-years: 0.98; 3-years: 1; 5-years: 1) and survival difference of high- and low risk groups (p=2.84e-10) of this model in TCGA dataset were obtained. The moderate predicting performance was observed in the independent cohort of GSE15459 and GSE62254. The results of the gene set enrichment analysis (GSEA) using high-and low risk group as phenotype indicated differential expression of tumor-related pathways., Conclusion: Thus, we constructed a reliable prognostic model for diffuse type gastric cancer, which should be beneficial for clinical therapeutic decision-making.

Cancer stem cells are undifferentiated cancer cells that have self-renewal ability, a high tumorigenic activity, and a multilineage differentiation potential. MicroRNAs play a critical role in regulating gene expression during carcinogenesis. Here, we investigated the role of miR-7 and the mechanism by which it is dysregulated in gastric cancer stem cells (GCSCs). The stem cell marker, CD44, was used to sort GCSCs by fluorescence-activated cell sorting. We found that CD44 (+) cells have higher invasiveness and form more number of sphere colonies than CD44 (-) cells. Quantitative real-time polymerase chain reaction (PCR) revealed that the miR-7-5p expression was remarkably downregulated in GCSCs but was significantly increased in the methionine-deprived medium. The downregulation of miR-7-5p results from the increased DNA methylation in the promoter region using the methylation-specific PCR. Overexpression of miR-7-5p reduced the formation of colony and decreased the invasion of GCSCs through targeting Smo and Hes1 and subsequent repressing Notch and Hedgehog signaling pathways in vitro. Notably, upregulating miR-7-5p inhibited the growth of tumor in the xenograft model. Hence, these data demonstrated that miR-7-5p represses GCSC invasion through inhibition of Smo and Hes1, which provides a potential therapeutic target of gastric cancer treatment., (© 2019 Wiley Periodicals, Inc.)

To estimate the diagnostic performance of acoustic radiation force impulse elastography in distinguishing between benign and malignant superficial lymph nodes, relevant articles published before October 31, 2018, in China and other countries were used. Conclusively, a total of 18 articles were analyzed. Sixteen studies used Virtual Touch tissue quantification (Siemens Healthineers, Erlangen, Germany), and 4 studies used Virtual Touch tissue imaging (Siemens Healthineers). After a meta-analysis, it was found that acoustic radiation force impulse elastography is an efficient method for detecting superficial lymph nodes. In addition, if the cutoff value for the shear wave velocity were less than 2.85 m/s, the summary sensitivity would increase, and the heterogeneity would be reduced., (© 2019 by the American Institute of Ultrasound in Medicine.)

The intrinsic limits of conventional ultrasound microbubble contrast agent greatly promoted the development and application of various nanomaterials for more efficient cancer ultrasound theranostics. Considerable successes have been achieved in the field of ultrasound molecular imaging and targeted therapy for tumor based on nanoparticulate theranostic agents. This review summarizes and discusses the emerging development on exploring organic and inorganic nanomaterials for ultrasound-based tumor diagnositic applications, and as synergistic agents for ultrasound targeted therapy in fighting cancer. The relationship between structure/composition and functionality of nanomaterials for ultrasound theranostic is discussed and revealed in detail. Finally, the further development and challenges facing clinical implementation of ultrasound nanomedicine are discussed. As a highly promising and valuable tumor-specific theranostic methodology, it is believed that ultrasound nanomedicine would pave a novel but efficient way for combating cancer., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Accumulating pre-clinical and clinical studies suggested that the renin-angiotensin system blockers (RASBs) possess anti-carcinogenic properties, and their use is associated with favorable outcomes in many types of cancers., Methods: A systematic literature search of relevant databases through January 2019 was conducted to identify studies assessing the RASBs on prognostic outcomes in digestive system malignancies patients on the basis of predetermined selection criteria for pooled hazard ratio (HR) with 95% confidence intervals (CIs). A total of 13 studies were included in the meta-analysis., Results: The meta-analysis showed that the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) resulted in a significant improvement in overall survival (HR 0.79; 95%CI 0.70-0.89; P < .000), cancer-specific survival (HR 0.81; 95%CI 0.73-0.90; P < .000) and recurrence-free survival (HR 0.68; 95%CI 0.54-0.85; P = .001), but not progression-free survival (HR 0.88; 95%CI 0.73-1.07; P = .183) and disease-free survival (HR 0.50; 95%CI 0.11-2.39; P = .103). Subgroup analysis indicated that the use of RASBs has a significant improvement of overall survival (OS) in pancreatic cancer, liver cancer, and gastric cancer. Two studies evaluated the dose-response relationship between ACEIs/ARBs therapy and survival and showed higher doses and better survival [(1-364 defined daily doses: odds ratio (OR) 0.89, 95%CI 0.78-1.01, P = .076), (≥365 defined daily doses: OR 0.54, 95%CI: 0.24-1.24, P = .148]., Conclusions: Meta-analysis of studies supports a beneficial association between use of RASBs and survival of digestive system malignancies.

Background Deep learning (DL) algorithms are gaining extensive attention for their excellent performance in image recognition tasks. DL models can automatically make a quantitative assessment of complex medical image characteristics and achieve increased accuracy in diagnosis with higher efficiency. Purpose To determine the feasibility of using a DL approach to predict clinically negative axillary lymph node metastasis from US images in patients with primary breast cancer. Materials and Methods A data set of US images in patients with primary breast cancer with clinically negative axillary lymph nodes from Tongji Hospital (974 imaging studies from 2016 to 2018, 756 patients) and an independent test set from Hubei Cancer Hospital (81 imaging studies from 2018 to 2019, 78 patients) were collected. Axillary lymph node status was confirmed with pathologic examination. Three different convolutional neural networks (CNNs) of Inception V3, Inception-ResNet V2, and ResNet-101 architectures were trained on 90% of the Tongji Hospital data set and tested on the remaining 10%, as well as on the independent test set. The performance of the models was compared with that of five radiologists. The models' performance was analyzed in terms of accuracy, sensitivity, specificity, receiver operating characteristic curves, areas under the receiver operating characteristic curve (AUCs), and heat maps. Results The best-performing CNN model, Inception V3, achieved an AUC of 0.89 (95% confidence interval [CI]: 0.83, 0.95) in the prediction of the final clinical diagnosis of axillary lymph node metastasis in the independent test set. The model achieved 85% sensitivity (35 of 41 images; 95% CI: 70%, 94%) and 73% specificity (29 of 40 images; 95% CI: 56%, 85%), and the radiologists achieved 73% sensitivity (30 of 41 images; 95% CI: 57%, 85%; P = .17) and 63% specificity (25 of 40 images; 95% CI: 46%, 77%; P = .34). Conclusion Using US images from patients with primary breast cancer, deep learning models can effectively predict clinically negative axillary lymph node metastasis. Artificial intelligence may provide an early diagnostic strategy for lymph node metastasis in patients with breast cancer with clinically negative lymph nodes. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Bae in this issue.

Background: Autophagy plays an important role in regulating cisplatin (CDDP) resistance in gastric cancer cells. However, the underlying mechanism of methioninase (METase) in the regulation of autophagy and CDDP resistance of gastric cancer cells is still not clear., Materials and Methods: Western blot was used to detect the levels of autophagy-related proteins, multidrug-resistant 1 (MDR-1), and FoxM1 protein. LncRNA HULC was detected by qRT-PCR. Cell viability was detected using CCK-8 assay. The interaction between lncRNA HULC and FoxM1 was confirmed by RNA pull-down and RIP assay., Results: Lentiviral vector carrying METase (LV-METase) suppressed autophagy and CDDP resistance of drug-resistant gastric cancer cells. LncRNA HULC was significantly downregulated in drug-resistant gastric cancer cells transfected with LV-METase. Besides, we found that lncRNA HULC interacted with FoxM1. In addition, METase suppressed autophagy to reduce CDDP resistance of drug-resistant gastric cancer cells through regulating HULC/FoxM1, and interfering HULC suppressed autophagy to reduce CDDP resistance of drug-resistant gastric cancer cells through regulating FoxM1. Finally, interfering HULC inhibited tumor growth in vivo., Conclusion: METase suppressed autophagy to reduce CDDP resistance of drug-resistant gastric cancer cells through regulating HULC/FoxM1 pathway.

Background: Elderly patients with diffuse large B-cell lymphoma (DLBCL) have a worse prognosis than younger patients, and the optimal treatment strategy for this group remains controversial. We conducted a retrospective analysis to investigate the clinical features and outcomes of elderly patients (>60 years) and to assess the impact of clinical and molecular factors on outcome in this age group., Methods: From April 2006 to December 2012, a total of 349 elderly patients with DLBCL from the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College were included in this analysis. Patients were further divided into two age groups (61-69 years and ≥70 years). We compared clinical characteristics and outcomes between groups., Results: Of 349 total patients, 204 (58.5%) were aged 61 to 69 years, and 145 (41.5%) patients were aged 70 years or older. Except for the Eastern Cooperative Oncology Group performance status, clinical characteristics were comparable between the two groups. With a median follow-up of 82 (range, 1-129) months, the 5-year overall survival (OS) and progression-free survival (PFS) rates were 51.9% and 45.8%, respectively. The 5-year OS rates for patients aged 61 to 69 years and those over 70 years were 58.3% and 42.8% (P = 0.007), respectively, and the 5-year PFS rates were 51.0% and 38.6% (P = 0.034). Treatment regimens including rituximab provided a higher 5-year OS rate (63.1% vs. 37.1%, P < 0.001) and PFS rate (56.6% vs. 31.8%, P < 0.001) than chemotherapy alone. For patients aged 61 to 69 years, chemotherapy plus rituximab resulted in a higher 5-year OS rate (66.7% vs. 46.4%, P = 0.002) and PFS rate (60.0% vs. 38.1%, P = 0.002) than chemotherapy alone. For patients aged ≥70 years, there was a marked survival advantage in patients who received chemotherapy plus rituximab (5-year OS rate: 57.7% vs. 25.4%, P < 0.001; 5-year PFS rate: 51.3% vs. 23.9%, P < 0.001) compared with that seen in those who received chemotherapy alone. Multivariate analysis established that stage III/IV disease, elevated lactate dehydrogenase (LDH), initial treatment, and chemotherapy with rituximab were independent risk factors for 5-year OS, and stage III/IV disease, elevated LDH, and chemotherapy with rituximab were independent risk factors for 5-year PFS for elderly patients with DLBCL., Conclusions: In comparison to patients aged 61 to 69 years, those aged ≥70 years have poorer survival. Prolonged survival is obtainable with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)-like in elderly Chinese patients in all age groups, indicating that the R-CHOP-like regimen should be considered for this population, even for those aged 70 years or older.

Artificial intelligence (AI) is gaining extensive attention for its excellent performance in image-recognition tasks and increasingly applied in breast ultrasound. AI can conduct a quantitative assessment by recognizing imaging information automatically and make more accurate and reproductive imaging diagnosis. Breast cancer is the most commonly diagnosed cancer in women, severely threatening women's health, the early screening of which is closely related to the prognosis of patients. Therefore, utilization of AI in breast cancer screening and detection is of great significance, which can not only save time for radiologists, but also make up for experience and skill deficiency on some beginners. This article illustrates the basic technical knowledge regarding AI in breast ultrasound, including early machine learning algorithms and deep learning algorithms, and their application in the differential diagnosis of benign and malignant masses. At last, we talk about the future perspectives of AI in breast ultrasound., Competing Interests: Conflict-of-interest statement: We declare that we do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.

Artificial intelligence (AI), particularly deep learning algorithms, is gaining extensive attention for its excellent performance in image-recognition tasks. They can automatically make a quantitative assessment of complex medical image characteristics and achieve an increased accuracy for diagnosis with higher efficiency. AI is widely used and getting increasingly popular in the medical imaging of the liver, including radiology, ultrasound, and nuclear medicine. AI can assist physicians to make more accurate and reproductive imaging diagnosis and also reduce the physicians' workload. This article illustrates basic technical knowledge about AI, including traditional machine learning and deep learning algorithms, especially convolutional neural networks, and their clinical application in the medical imaging of liver diseases, such as detecting and evaluating focal liver lesions, facilitating treatment, and predicting liver treatment response. We conclude that machine-assisted medical services will be a promising solution for future liver medical care. Lastly, we discuss the challenges and future directions of clinical application of deep learning techniques., Competing Interests: Conflict-of-interest statement: There is no conflict of interest associated with any of the senior author or other coauthors who contributed their efforts in this manuscript.

Background: Gastric cancer (GC) severely threatens human life, and METase seemed to inhibit tumor growth. However, the potential mechanism underlying it is still unclear., Methods: Both clinical tissues and cell lines were used in the present study. SNHG5 and miR-20a expressions were determined using real-time PCR. Western blot was performed to determine the expression of autophagy-related proteins. The interaction between miR-20a and SNHG5 was determined using luciferase reporter assay and RNA immunoprecipitation (RIP)., Results: The expression of SNHG5 was decreased in GC tissues and cell lines. Overexpressed METase significantly promoted cell apoptosis and autophagy, as well as the expression of SNHG5. SNHG5 directly regulated the expression of miR-20a. GC cells transfected with pcDNA-SNHG5 significantly promoted cell apoptosis and autophagy, while the co-transfected with miR-20a mimic dramatically reversed the effects of pcDNA-SNHG5. Overexpressed METase significantly promoted cell autophagy, which was abolished by down-regulated SNHG5., Conclusion: Overexpressed METase promoted cell apoptosis and autophagy via up-regulating the expression of SNHG5 and down-regulating miR-20a in GC., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To investigate the clinical outcome of the patients with primary diffuse large B-cell lymphoma（DLBCL）., Methods: Clinical data of 148 patients with DLBCL in our hospital and cancer hospital from March 2006 to April 2016 were retrospectively analyzed. Kaplan-Meier analysis was used to estimate progression-free survival（PFS）and overall survival（OS）., Results: 5-year OS and PFS rates were 85% and 69%，respectively. The survival analysis showed that 5-year OS rate of R-CHOP group was significantly higher than that of CHOP alone group（89% vs. 70%，P<0.05）. In univariate analysis，several clinical factors，such as older age（>60 years），poor ECOG score（≥2），advanced stage（Ⅲ-Ⅳ），higher IPI score（≥3），CHOP alone and absence of radiotherapy related with poor survival rate. Furthermore，multivariate analysis showed that age>60 year significantly related with the worse OS., Conclusion: Age >60 year is an important independent prognostic factor to predict worse OS or PFS.

The prognosis and optimal therapy for high-risk early-stage extranodal nasal-type natural killer/T-cell lymphoma (NKTCL) are not well defined. This study was conducted to evaluate the prognostic factors and treatment outcomes in patients with stage II NKTCL of the upper aerodigestive tract (UADT-NKTCL). One hundred and twenty-four patients with stage II UADT-NKTCL were enrolled. Primary tumors were located in the nasal cavity (n = 53) or extranasal UADT (n = 71). Eighty-four patients were treated with combined modality therapy (CMT), and 40 patients were treated with radiotherapy alone (n = 30) or chemotherapy alone (n = 10). The 5-year overall survival (OS) and progression-free survival (PFS) rates for all stage II patients were 60.1% and 47.8%, respectively. Primary location and disease extent were the important prognostic factors in univariate and multivariate analyses. CMT significantly improved survival. The 5-year OS and PFS rates were 71.2% and 56.7% for CMT, compared with 35.1% (p < 0.001) and 26.7% for single modality therapy (p < 0.001). Survival differences between CMT and single modality therapy were also observed in nasal and extranasal subgroups of UADT-NKTCL. This retrospective study showed significant improvements in OS and PFS in patients who received both chemotherapy and radiotherapy for stage II NKTCL. The findings need further validation in other datasets.

This retrospective analysis compared standard regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) with the dose-dense ABVD regimen (ABVD-21) in terms of efficacy and toxicity. Patients who had early-stage unfavorable or advanced Hodgkin's lymphoma (HL) according to German Hodgkin Study Group criteria from March 1999 to February 2011 were analyzed for treatment response, long-term survival and hematological toxicity. There were 85 patients in the ABVD-21 group and 118 patients in the ABVD group respectively. The complete remission rates after completion of treatment were 92.9% and 90.7% for ABVD-21 and ABVD, respectively. During a median follow-up period of 62 months, no significant difference was found in projected 10-year progression-free survival (PFS) and overall survival (OS) rates (84.7% and 94.1% respectively for ABVD-21; 81.4% and 91.5% for ABVD). Subgroup analyses showed that ABVD-21 was significantly better than ABVD for patients with IPS≥3 in terms of PFS and OS rates. Grade 3 to 4 leukopenia (51.8% vs. 28.8%, P=0.001) and neutropenia (57.6% vs. 39.0%, P=0.009) were more common with ABVD-21. We were led to conclude that dose-dense ABVD did not result in better tumor control and overall survival than did ABVD for early-stage unfavorable HL. However, patients at high risk, for example, with IPS≥3, may benefit from dose-dense ABVD.

Purpose: To investigate, in a large cohort of patients, the immunophenotypic and clinical differences of nasal and extranasal extranodal nasal-type natural killer/T-cell lymphoma of the upper aerodigestive tract (UADT-NKTCL) and examine the relevance of the immunophenotype on the clinical behavior, prognosis, and treatment., Methods and Materials: A total of 231 patients with UADT-NKTCL were recruited. One hundred eighty-one patients had primary location in the nasal cavity (nasal UADT-NKTCL), and 50 patients had primary extranasal UADT-NKTCL., Results: Patients with extranasal UADT-NKTCL had more adverse clinical features, including advanced-stage disease, regional lymph node involvement, B symptoms, and poor performance status, than patients with nasal UADT-NKTCL. In addition, CD56 and granzyme B were less frequently expressed in extranasal UADT-NKTCL. The 5-year overall survival rate was 74.1% for the entire group and 76.0% for early-stage disease. The 5-year overall survival rate for extranasal UADT-NKTCL was similar or superior to that of nasal UADT-NKTCL for all disease stages (76.9% vs 73.4%, P=.465), stage I disease (75.9% vs 79.2%, P=.786), and stage II disease (83.3% vs 50.3%, P=.018). CD56 expression and a Ki-67 proliferation rate ≥ 50% predicted poorer survival for extranasal UADT-NKTCL but not for nasal UADT-NKTCL., Conclusions: Patients with nasal and extranasal UADT-NKTCL have significantly different clinical features, immunophenotypes, and prognosis. Extranasal UADT-NKTCL should be considered as a distinct subgroup apart from the most commonly diagnosed prototype of nasal UADT-NKTCL., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: This study aimed to compare the clinical characteristics and prognosis of Waldeyer ring extranodal nasal-type natural killer (NK)/T-cell lymphoma (WR-NKTCL) and Waldeyer ring diffuse large B-cell lymphoma (WR-DLBCL)., Methods: Consecutive diagnoses of 122 WR-DLBCL and 44 WR-NKTCL patients, receiving mainly primary radiotherapy in early-stage WR-NKTCL and primary chemotherapy in early-stage WR-DLBCL, were reviewed., Results: WR-NKTCL occurred predominately in young males, as nasopharyngeal stage I disease with B-symptoms, extranodal dissemination, and involving adjacent structures. WR-DLBCL was mainly stage II tonsillar disease with regional lymph node involvement. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 74% and 67% in WR-DLBCL, respectively, and 68% (P=0.468) and 59% (P=0.303) in WR-NKTCL. In stages I and II disease, WR-DLBCL 5-year OS and PFS were 79% and 76% compared with 72% (P=0.273) and 62% (P=0.117) in WR-NKTCL. In stage I disease, WR-DLBCL 5-year OS and PFS were 81% and 81%, compared with 76% (P=0.394) and 63% (P=0.236) in WR-NKTCL. In addition, the prognostic factors and failure patterns in WR-DLBCL and WR-NKTCL differed substantially., Conclusions: These results indicate that remarkable clinical disparities exist between WR-DLBCL and WR-NKTCL; however, different treatment strategies for each can result in similarly favorable prognoses.

Abstract The aim of this study was to evaluate the prognostic importance of rituximab and radiotherapy in patients with primary mediastinal large B-cell lymphoma (PMBCL) receiving doxorubicin-containing chemotherapy. Seventy-nine patients with PMBCL received CHOP chemotherapy with (n = 39) or without rituximab (n = 40), and 60 patients received additional radiotherapy. Patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) had significantly superior survival rates. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 83.7% and 76.7% for R-CHOP, compared with 48.3% (p = 0.011) and 44.2% (p = 0.012) for CHOP, respectively. Similarly, the 5-year OS and PFS rates for early stage patients were 93.8% and 84.6% with R-CHOP, and 52.0% (p = 0.002) and 46.6% (p = 0.003) with CHOP, respectively. Patients treated with chemotherapy and radiotherapy had better survival and local control (LC) rates compared with chemotherapy alone. The 5-year OS, PFS and LC rates for early stage patients were 73.6%, 69.9% and 92.6% for chemotherapy and radiotherapy, and 50.8% (p = 0.076), 36.9% (p = 0.008) and 56.4% (p < 0.001) for chemotherapy alone, respectively. Early stage patients treated with R-CHOP and radiotherapy had 5-year OS, PFS and LC rates of 96.4%, 85.9% and 93.1%. R-CHOP plus consolidation radiotherapy was associated with excellent survival and LC rates.

Purpose: Early stage peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is rare. The purpose of this study was to evaluate the outcome of treatment as well as the potential role of radiation therapy in PTCL-NOS., Methods and Materials: Thirty-five patients with early stage PTCL-NOS were included. There were 13 patients with stage I disease and 22 with stage II. All patients except 1 received doxorubicin-based chemotherapy alone (n=13) or a combination of chemotherapy and radiation therapy (CMT) (n=21)., Results: The 3-year overall survival (OS) and progression-free survival (PFS) rates for the entire group were 41.3% and 25.7%, respectively. The addition of radiation therapy to chemotherapy significantly improved OS and PFS in early stage PTCL-NOS. The 3-year OS and PFS rates were 49.7% and 33.3% for CMT, compared with 23.1% (P=.042) and 15.4% (P=.035) for chemotherapy alone, respectively. The prognosis for patients who achieved a complete response (CR) was significantly better than that observed in those who did not achieve a CR., Conclusions: Despite the aggressive clinical course of early stage PTCL-NOS, additional radiation therapy has a significant impact on outcome. The integration of local radiation therapy into more effective systemic therapies may further improve survival., (Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.)

This study was conducted to evaluate the efficacy and safety of gemcitabine-based combination regimen in patients with peripheral T-cell lymphoma (PTCL). Between May 2007 and August 2011, 26 consecutive patients with PTCL were enrolled in this study. Of these 26 patients, histology was extranodal NK/T-cell lymphoma, nasal type in 14 (53.9 %), peripheral T-cell lymphoma, not otherwise specified in nine (34.6 %), anaplastic large cell lymphoma, ALK negative in three (11.5 %). The majority of patients had newly diagnosed (65.4 %) and advanced (80.8 %) diseases. Treatment regimen was DIMG (dexamethasone, ifosfamide, methotrexate, and gemcitabine) given to the first 6 patients, and GDP (gemcitabine, dexamethasone, and cisplatin) given to the remaining 20 patients. The median follow-up time was 25 (range 7-60) months. The overall response rate was 88.5 %. Twelve (46.2 %) patients achieved complete remission, 11 (42.3 %) patients achieved partial remission, and 1 (3.8 %) patient had stable disease (SD), two (7.7 %) patients had progressive diseases. The 1- and 2-year progression-free survival rates were 58.7 and 45.9 %, while 1- and 2-year overall survival rates for all patients were 80.6 and 63.7 %, respectively. Adverse events included grade 3 or 4 neutropenia (35.0 %) and thrombocytopenia (15.0 %) from patients treated with GDP. Grade 3 or 4 neutropenia and thrombocytopenia were 100.0 and 66.7 %, respectively, for patients who received DIMG regimen. Our study has demonstrated that the gemcitabine-based combination regimen, especially GDP regimen, is safe and well tolerated with promising clinical activity in patients with PTCLs.

The aim of this study was to analyze outcomes in adult patients with early stage systemic anaplastic large-cell lymphoma (ALCL) treated with doxorubicin-based chemotherapy and radiotherapy. Forty-six adult patients with early stage systemic ALCL received chemotherapy followed by radiotherapy. All patients except two received chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or a CHOP-like regimen. Twenty patients had stage I disease, and 26 patients had stage II disease. The 5-yr overall survival (OS), progression-free survival (PFS), and local control rates for all patients were 84.4%, 63.6%, and 90.8%, respectively. The 5-yr OS and PFS rates were 95.0% and 77.4% for Ann Arbor stage I disease, and 75.1% and 51.7% for stage II disease, respectively. Lymph node involvement was the main pattern of disease progression or relapse for these patients. Adult patients with early stage systemic ALCL treated with doxorubicin-based chemotherapy and radiotherapy had a favorable prognosis., (© 2013 John Wiley & Sons A/S.)

The clinical value of plasma Epstein-Barr virus (EBV) DNA has not been evaluated in patients with early-stage extranodal nasal-type NK/T-cell lymphoma (NKTCL) receiving primary radiotherapy. Fifty-eight patients with stage I disease and 11 with stage II disease were recruited. High pretreatment EBV-DNA concentrations were associated with B-symptoms, elevated lactate dehydrogenase levels, and a high International Prognostic Index score. EBV-DNA levels significantly decreased after treatment. The 3-year overall survival (OS) rate was 82.6% for all patients. Stage I or II patients with a pretreatment EBV-DNA level of ≤ 500 copies/mL had 3-year OS and progression-free survival (PFS) rates of 97.1% and 79.0%, respectively, compared with 66.3% (P = .002) and 52.2% (P = .045) in patients with EBV-DNA levels of > 500 copies/mL. The 3-year OS and PFS rates for patients with undetectable EBV-DNA after treatment was significantly higher than patients with detectable EBV-DNA (OS, 92.0% vs 69.8%, P = .031; PFS, 77.5% vs 50.7%, P = .028). Similar results were observed in stage I patients. EBV-DNA levels correlate with tumor load and a poorer prognosis in early-stage NKTCL. The circulating EBV-DNA level could serve both as a valuable biomarker of tumor load for the accurate classification of early-stage NKTCL and as a prognostic factor.

Objective: The aim of this study was to investigate the clinicopathological characteristics, effective treatment and prognosis in childhood and adolescent Hodgkin's lymphoma., Methods: A total of 88 patients with childhood and adolescent Hodgkin's lymphoma were treated in the Cancer Hospital of CAMS from 1998 to 2005. The clinicopathological and follow-up data of the patients were retrospectively reviewed. The survival rate was calculated by Kaplan-Meier method and compared by log-rank test. COX multivariate prognosis analysis was performed., Results: The 2-year event-free survival rate of the 88 patients was 86.4%, the 5-year event-free survival rate was 61.4%, and the 5-year overall survival rate was 95.5%. Univariate analysis showed that the stage of disease (P = 0.033), "B" symptoms (P = 0.028), bulky disease (P = 0.007), splenomegaly (P = 0.050), LDH elevation (P = 0.020), chemotherapy regimen (P = 0.003) were prognostic factors in the 5-year event-free survival rate. Splenomegaly (P = 0.039), LDH elevation (P = 0.033), chemotherapy regimen (P = 0.008) were prognostic factors of 5-year overall survival rate. Multivariate analysis showed that chemotherapy regimen (P = 0.033), stage of disease (P = 0.023), LDH elevation (P = 0.008), "B" symptoms (P = 0.044), bulky disease (P = 0.009) were independent prognostic factors of 5-year event-free survival rate. The chemotherapy regimen (P = 0.012) and LDH elevation (P = 0.046) were independent prognostic factors of 5-year overall survival rate., Conclusions: The non-ABVD chemotherapy regimen, stage IV disease, LDH elevation, associated with "B" symptoms and bulky disease are independent prognostic factors of 5-year event-free survival rate. LDH elevation and non-ABVD chemotherapy regimen are independent prognostic factors of 5-year overall survival rate.

Background: Nasal diffuse large B-cell lymphoma (DLBCL) is rare. The objective of this study was to evaluate the clinical features and treatment outcomes of patients with nasal DLBCL., Methods: Twenty-five patients were included in the study. All patients received combination chemotherapy with or without radiotherapy., Results: Patients with nasal DLBCL usually were older and were predominantly men with early stage disease, low frequency of B symptoms and elevated lactate dehydrogenase (LDH), good performance status, and a low-risk international prognostic index (IPI) score. The overall response rate after initial treatment was 76%, the 3-year overall survival (OS) rate for the whole group was 44%, and the median OS was 35 months. Performance status and IPI were significant prognostic factors for OS. For patients with IPI scores of 0 or 1, the 3-year OS rate was 54%, and the median OS was 52 months compared with 17% and 11 months, respectively, for patients with IPI scores of 2 or 3 (P = .033). The prognosis for patients who achieved a complete response (CR) was significantly better than that for patients who did not achieve a CR. Extranodal spread was the primary pattern of failure., Conclusions: The current results indicated that primary nasal DLBCL appears to have distinct clinical features; its poor outcome and propensity for extranodal failure illustrate the need for innovative therapies., (Copyright © 2011 American Cancer Society.)

A pot experiment was carried out to investigate the effects of three organic amendments (organic carbon material, rapeseed cake, and pig manure) on the growth and heavy metal uptake of rice on a heavy metal mixed contaminated paddy soil. Applying rapeseed cake and pig manure could mitigate the toxic effect of heavy metals on rice plant. The two organic amendments increased the shoot biomass and grain yield significantly, and decreased the heavy metal concentration in brown rice. Under the application of organic carbon material, rice growth was inhibited. As compared with the control, applying rapeseed cake and pig manure increased the grain yield by 128.3% and 67.9%, and decreased the Cd, Cu, and Zn concentrations in brown rice by 47.6%, 35.2% and 21.5%, and 9.5%, 21.2% and 9.3%, respectively. The shoot biomass and its total accumulation of Cd, Cu, and Zn had significant negative correlations with the soil DTPA-extractable heavy metals.

Background: This study aimed to evaluate the failure patterns and clinical implications in patients with early stage nasal natural killer (NK)/T-cell lymphoma treated with primary radiotherapy., Methods: Two-hundred fourteen patients were included. There were 182 cases of stage I and 32 cases of stage II disease. Patients received radiotherapy alone (n = 96) or radiotherapy and chemotherapy (n = 118). The median dose was 50 grays, and most patients received doxorubicin-based chemotherapy., Results: The 5-year overall survival (OS) and progression-free survival rates for all patients were 72% and 65%, respectively. Sixty-three patients experienced treatment failure. The 5-year cumulative incidences of locoregional, systemic, and overall failures were 12.0%, 25.5%, and 32.9%, respectively. Stage and paranasal extension were significant predictors for systemic failure. The 5-year cumulative incidence of systemic failure was 22.6% for stage I disease versus 42.7% for stage II disease (P < .001), and 16.9% for limited disease versus 30.4% for paranasal extension (P < .001), respectively. Adding chemotherapy to extended involved-field radiotherapy did not significantly decrease the systemic failure rate nor improve survival. The cumulative incidence of systemic failure and OS rate at 5 years were 24.1% and 74.4% for combined modality therapy compared with 28.5% (P = 0.758) and 69.8% (P = 0.529) for radiotherapy alone. A very low incidence of cervical lymph node or central nervous system relapse was observed., Conclusions: Patients with early stage nasal NK/T-cell lymphoma have excellent locoregional control and favorable prognosis with radiotherapy, but patients with stage II disease or paranasal extension are at high risk of systemic failure, emphasizing the importance of integration of optimal radiotherapy with innovative systemic therapy., (Copyright © 2011 American Cancer Society.)

Effects of current Cd contamination levels on microbial biodiversity were studied under the typical Cd contaminated soils in the Yangtze Basin. Purple soil and alluvial soil potted with a poplar (Populus deltoides x Populus nigra) were selected, and the culturable soil microbial amounts by flat method, microbial biomass and bacterial community structure by PCR-DGGE were investigated. Cd supplies significantly increased the culturable amounts of bacteria and actinomyces in purple soil, but decreased the culturable amounts of fungi and the content of microbial biomass N. Fingerprint of DGGE also showed that bacterial community structure have obviously changed under different Cd supplies. In contrast, the lower Cd supplies slightly increased the culturable amounts of bacteria and fungi in alluvial soil, but higher Cd supply treatment decreased the culturable amounts of bacteria, actinomyces and fungi, and the content of microbial biomass N. However, only a slight change was observed under different Cd supplies by DGGE fingerprint. Additionally, there were few effects of Cd supplies on the content of microbial biomass C in both purple soil and alluvial soil. The results provided basic data to understand the effects of present Cd contamination levels on soil microbial characteristics.

This study aimed to determine whether the phenotypic characteristics of the two subtypes of CD56+ and CD56- lymphoma have relevance for their clinical behavior and prognosis. The immunophenotypes of all patients were confirmed using standard criteria for CD20, CD3ε, CD56, cytotoxic molecules (T-cell intracellular antigen-1 [TIA-1] and granzyme B), and Ki-67, and in situ hybridization for Epstein-Barr virus (EBV)-encoded RNA (EBER). CD56 was expressed in 90 of 118 (76.3%) patients. The majority (83.3%) of patients with nasal natural killer/T-cell lymphoma (NKTCL) presented with CD56+ lymphoma, whereas patients with NKTCL of the extranasal upper aerodigestive tract were more likely to have CD56- lymphoma (53.6%, p < 0.000). A lower percentage of expression of granzyme B and Ki-67 (>50%) was found in patients with CD56- lymphoma compared with those with CD56+ lymphoma (p <0.05). The clinical characteristics and prognosis were comparable between patients with CD56+ and CD56- lymphomas. The corresponding overall survival and progression-free survival rates were 74.1% and 56.7%, respectively, for patients with CD56+ lymphoma compared with 81.6% and 60.5% for those with CD56- lymphoma (p > 0.05). There was no clinical or prognostic significance in determining the two subtypes of CD56+ and CD56- NKTCL based on their immunophenotypic profiles, which has clinical implications for pathological diagnosis and insight into disease behavior.

Objective: To retrospectively analyze the clinical features and prognostic factors of patients with angioimmunoblastic T-cell lymphoma (AITL)., Methods: The clinicopathological and follow-up data of 18 AITL patients undergoing integrated treatment from Feb. 1998 to April 2009 in our department were retrospectively analyzed. All of the patients received CHOP-like regimens as initial chemotherapy, including 4 once treated with radiotherapy and 1 with high dose therapy followed by autologous stem cell transplantation (HDT-ASCT) as upfront consolidation therapy. B-cell, T-cell and NK-cell subgroup proportions in the peripheral blood were tested by flow cytometry in 6 patients., Results: The median age of the 18 patients was 55 years, male and female ratio was 2.6:1. Seventy-two percent of the patients were in an advanced stage. 72% of them had B symptoms, 69% hypergammaglobulinemia, 60% elevated LDH and 47% anemia. Forty-four percent achieved CR after initial treatment with CHOP-like regimens. With the median follow-up of 26 months, the overall 2-year survival and disease free survival (DFS) rates were 62.2% and 44.4%, respectively. In the univariate analysis, only age > 30 years and primary refractory disease adversely affected overall survival (OS); age > 30 years, advanced stage, B symptoms and splenomegaly adversely affected DFS. Four patients suffered from severe pneumonia during treatment, 2 of them died of respiratory failure. Flow cytometry of peripheral blood lymphocytes showed that 5 of the 6 tested cases had decreasing proportion of CD3(+)CD4(+) T cells, B cells and NK cells but elevated CD3(+)CD8(+) T cells. Two heavily treated patients achieved partial and complete response by thalidomide therapy, with a progression free survival (PFS) of 2 and 6+ months, respectively., Conclusion: AITL patients do not response well to CHOP-like regimens chemotherapy. Age < 30 years and sensitive to initial chemotherapy are associated with prolonged OS. Effectiveness of thalidomide in the treatment of AITL deserves further investigation. Peripheral blood lymphocytes test indicates that AITL patients suffered from both natural and acquired immune defects.

Objective: To explore the clinical presentation, treatment and prognosis study of primary subcutaneous panniculitis-like T-cell cutaneous lymphoma (SCPTCL)., Methods: Ten cases of SCPTCL, treated in our hospital from January 1999 to January 2009, were included in this study. Their clinicopathological data were reviewed and analyzed retrospectively., Results: the median age was 50.5 years (range: 10 - 58), 4 males and 6 females. There were seven CD56 positive, two negative cases and 1 unclear case. Four cases had repeatedly nodules regressed spontaneously without treatment before diagnosis and new nodules appeared at different sites. Seven patients presented with multiple subcutaneous nodules or deeply seated plaques, most commonly on the extremities and trunk. Ulceration of nodules occurred in 3 cases, and the lesions were painful in five cases. The lesions appeared nodules at the beginning, and then gradually grew into tumors. Four patients had abnormal liver function and one patient had hemophagocytic syndrome (HPS), four patients had lymphadenopathy or visceral involvement. Three cases with single lesion underwent surgical excision in combination with chemotherapy or chemotherapy/radiotherapy. One case lost follow up, and two cases live without disease. Among the seven patients with multiple lesions, lymphadenopathy or visceral involvement, one underwent local surgical excision and is alive without disease, six of them received chemotherapy or multi-modality treatment mainly with chemotherapy. Three of these 6 cases are alive without progression, one used histone deacetylase inhibitors after progression and obtained partial regression, and 2 died. The median follow-up for all the 10 patients was 44 months (range: 14 - 99). The progression free survival was 66.7% (6/9), and overall survival was 77.8% (7/9)., Conclusion: SPTCL has an indolent course, some lesions can regress spontaneously and relapse again. Patients with single lesion may live long-term without disease after multimodality therapy. Patients with multiple lesions or extracutaneous involvement are sensitive to CHOP-like regimen, but the duration of remission is short. Histone deacetylase inhibitors may be a promising drug in the treatment for SCPTCL relapse.

Background: : The objective of this study was to compare the clinical features and prognosis of patients with diffuse large B-cell lymphoma (DLBCL) of Waldeyer ring (WR-DLBCL) and patients with lymph node DLBCL (N-DLBCL)., Methods: : One hundred eighty-one patients with WR-DLBCL and N-DLBCL were reviewed. There were 57 patients with stage I disease, 83 patients with stage II disease, 26 patients with stage III disease, and 15 patients with stage IV disease. Among them, 101 patients had primary N-DLBCL, and 80 patients had primary WR-DLBCL., Results: : Patients with WR-DLBCL and N-DLBCL usually presented at an older age and had localized disease, a low frequency of B symptoms, a good performance status, and a low-risk International Prognostic Index (IPI) score. Compared with patients who had N-DLBCL, patients who had WR-DLBCL presented with more stage II disease and lower tumor burdens. The overall response rate after treatment was similar in both groups. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 76% and 61% in patients with WR-DLBCL, respectively, and 56% and 50% in patients with N-DLBCL, respectively (P = .119 for OS; P = .052 for PFS). IPI scores and elevated beta2-microglobulin and LDH levels were associated with a poor prognosis for patients who had WR-DLBCL; whereas bulky tumor, elevated beta2-microglobulin levels, and IPI scores were associated with poor OS for patients who had N-DLBCL., Conclusions: : The current results supported the continued inclusion of WR-DLBCL as a lymph node group in the staging of DLBCL. Patients with WR-DLBCL had clinical features and prognosis similar to those of patients with N-DLBCL. Cancer 2009. (c) 2009 American Cancer Society.

Objective: To retrospectively analyze and compare the treatment efficiency of CHOP-based regimens with or without high-dose consolidation treatment combined with hematopoietic stem cell transplantation (HDT-HSCT) in the patients with lymphoblastic lymphoma (LBL)., Methods: From 1989 to 2004, totally 63 patients with LBL were initially treated with a standard CHOP-based regimen. Forty-two of the 63 patients achieved complete response (CR), 26 of those subsequently received consolidation HDT-HSCT, while the other 16 had 6-8 cycles of standard CHOP-based treatment only., Results: Of the 63 patients, 57 had a T-LBL and 6 B-LBL, with a median age of 20 years, 19 (30.2%) had a stage I-II diseases and 44 (69.8%) stage III-IV diseases, 61.9% presented with a mediastinal mass. Bone marrow involvement presented in 28.6% of the patients. Fourteen percent had central nervous system involvement. The median follow-up period was 24 months, and the estimated 5-year overall survival and disease-free survival of this series was 31.2% and 29.3%, respectively. Of the 42 patients who achieved CR, the 5-year OS rate of the patients who received HDT-HSCT as a consolidation therapy was 59.8% versus 14.6% of the patients treated by CHOP-based regimens alone (P=0.004). Bone marrow involvement, age > or =20 years, short response duration and primary refractory disease were factors significantly associated with poor outcome. Among the 18 patients with bone marrow involvement, 3 received allogeneic HSCT and were all still alive at the follow up time of 22, 32 and 37 months, respectively, while another 4 received auto-HSCT and all died of the disease within 14 months., Conclusion: Short term treatment with a CHOP-based regimen is not sufficient for the patients with lymphoblastic lymphoma. High-dose consolidation treatment and hematopoietic stem cell transplantation may improve overall survival and disease free survival. Bone marrow involvement, age >20 years, and short response duration and primary refractory disease are all the factors significantly associated with poor outcome. For the patients with bone marrow involvement, allohematopoietic stem cell transplantation is superior to auto-hematopoietic stem cell transplantation.

Objective: To compare the efficacy of chemotherapy alone, radiotherapy alone and combined-modality therapy in the treatment for early-stage Hodgkin's lymphoma (HL)., Methods: From 1999 to 2002, totally 150 patients with stage I or II HL were treated in our hospital. They were stratified into several groups based on initial treatment strategy: chemotherapy alone (CT group, n = 22), radiotherapy alone (RT group, n = 18), combined-modality therapy (CMT group, n = 109) and surgical resection (SR group, n = 1). Chemotherapy regimens were mainly ABVD (adriamycin, bleomycin, vinblastine and dacarbazine) and MOPP (mechlorethamine, vincristine, procarbazine and prednisone). Radiotherapy modes included involved field radiotherapy (IFRT), extended field radiotherapy (EFRT) and sub-total nodal irradiation (STNI)., Results: The pathological types included nodular sclerosis (NS, n = 84), mixed-cellularity (MC, n = 39), lymphocyte-predominant (LP, n = 23), lymphocyte-depleted (LD, n = 3) and nodular lymphocyte predominant Hodgkin's disease (NLPHD, n = 1). Of those, 72 were evaluble in terms of prognostic factors. No poor prognostic factor was found in 36.1% or 29.2% of the patients according to EORTC or GHSG criteria, respectively. There were 33 patients with complete response (CR), 109 with partial response (PR), 5 with stable disease (SD) and 3 with progressive disease (PD) after initial therapy. The median follow-up period was 71.5 months. The overall 7-yr survival rate was 89.3%, and treatment failure rate at 6 years was 18.8%. The response rate of CMT group was superior to that of CT group, and the patients with nodular sclerosis or mixed-cellularity type had significantly lower risk of treatment failure (P = 0.009 and 0.019, respectively). The multivariate analysis revealed that the treatment strategies affected the prognosis significantly. The risk of failure of chemotherapy alone was 2.52 times higher than that of combined-modality therapy (P = 0.004). No predictive factor affecting OS was identified by either univariate or multivariate analysis. The patients in CMT group suffered more adverse effects than those in either CT or RT groups, which mainly consisted of leucopenia, alopecia and gastrointestinal symptoms., Conclusion: Combined-modality therapy is more effective than chemotherapy alone or radiotherapy alone in the treatment for early stage Hodgkin's lymphoma. Though its acute adverse effects are more severe than that of chemotherapy or radiotherapy alone, it may reduce the risk of treatment failure.