Subcellular localization of nucleolar protein 14 and its proliferative function mediated by miR-17-5p and E2F4 in pancreatic cancer.

Pancreatic cancer is one of the most lethal malignancies worldwide. Acquiring infinite proliferation ability is a key hallmark and basis of tumorigenesis. NOP14 is an identified ribosome biogenesis protein that plays potential roles in cell proliferation. However, the function and molecular mechanism of NOP14 remain ambiguous in most human cancers. In this study, we first investigated the subcellular localization and expression of NOP14 by multiple quantitative assays in pancreatic cancer. We confirmed that NOP14 was mainly localized in nucleolus in human pancreatic cancer cells. Then we studied the regulatory effects of this nucleolus protein on tumor cell proliferation in vitro. NOP14 was demonstrated to play a dominant pro-proliferation role in pancreatic cancer. Furthermore, we identified miR17-5p as a downstream target of NOP14. Transfection of miR17-5p mimics or inhibitors rescued the down- or upregulated effect of NOP14 on cell proliferation by regulating expression of P130. In addition, NOP14 induced expression of transcription factor E2F4 independent of miR17-5p/P130 signaling, which simultaneously activated a set of targeted genes, such as CCNE1, PIM1, AKT1 etc., to promote tumor proliferation. These findings might provide novel insights for better understanding the diverse function of NOP14 in human malignancies to develop new strategies for targeted therapy.

ALDH2C4 regulates cuticle thickness and reduces water loss to promote drought tolerance.

In Arabidopsis thaliana, ALDH2C4 encodes coniferaldehyde dehydrogenase, which oxidizes coniferaldehyde to ferulic acid. Drought stress is one of the important abiotic stresses affecting plant growth. However, the role of ferulic acid in drought resistance is unknown. To investigate the contribution of ferulic acid to cuticle composition and drought resistance, we used two Arabidopsis aldh2c4 mutant lines. Compared with wild-type (WT) leaves, ferulic acid contents were significantly lower (by more than 50 %) in mutants. The mutants also had lower amounts of cutin and wax, primarily due to reductions in C18:2 dioic acid and alkanes, respectively. Furthermore, the leaves of the mutant plants exhibited greater rates of water loss and released chlorophyll faster than WT leaves when immersed in 80 % ethanol, indicating a defective cuticle barrier. The growth of aldh2c4 mutants was severely inhibited, and their leaves showed a higher degree of wilting relative to the WT plants under drought conditions. In aldh2c4 complementation lines, the growth inhibition of the mutant plants under drought stress was alleviated. Taken together, our results demonstrate that ferulic acid plays an important role in the composition and structural properties of the cuticle and that a ferulic acid deficiency in the cutin leads to reduced drought tolerance.

Plant Salinity Sensors: Current Understanding and Future Directions.

Salt stress is a major limiting factor for plant growth and crop yield. High salinity causes osmotic stress followed by ionic stress, both of which disturb plant growth and metabolism. Understanding how plants perceive salt stress will help efforts to improve salt tolerance and ameliorate the effect of salt stress on crop growth. Various sensors and receptors in plants recognize osmotic and ionic stresses and initiate signal transduction and adaptation responses. In the past decade, much progress has been made in identifying the sensors involved in salt stress. Here, we review current knowledge of osmotic sensors and Na+ sensors and their signal transduction pathways, focusing on plant roots under salt stress. Based on bioinformatic analyses, we also discuss possible structures and mechanisms of the candidate sensors. With the rapid decline of arable land, studies on salt-stress sensors and receptors in plants are critical for the future of sustainable agriculture in saline soils. These studies also broadly inform our overall understanding of stress signaling in plants.

Root Na+ Content Negatively Correlated to Salt Tolerance Determines the Salt Tolerance of Brassica napus L. Inbred Seedlings.

Soil salinization is a major environmental stressor that reduces the growth and yield of crops. Maintaining the balance of ions under salinity is vital for plant salt tolerance; however, little is known about the correlation between the salt tolerance of crops and the ion contents of their roots and shoots. Here, we investigated the poorly understood salt-tolerance mechanisms, particularly regarding ion contents (particularly Na+), in Brassica napus subsp. napus L., an agriculturally important species. Twenty B. napus inbred lines were randomly chosen from five salt-tolerance categories and treated with increasing concentrations of NaCl (0-200 mmol) for this work. We found that the root Na+ content is the most correlated limiting factor for the salt tolerance of B. napus; the higher the salt tolerance, the lower the root Na+ content. Correspondingly, the Ca2+/Na+ and K+/Na+ ratios of the roots were highly correlated with B. napus salt tolerance, indicating that the selective absorption ability of these ions by the roots and their translocation to the shoots play a pivotal role in this trait. These data provide a foundation for the further study of the molecular mechanisms underlying salt tolerance and for breeding salt-tolerant B. napus cultivars.

Intraoperative radiotherapy vs concurrent chemoradiotherapy in the treatment of patients with locally advanced pancreatic cancer.

PURPOSE: The purpose of the multi-institutional retrospective study was to evaluate whether intraoperative radiotherapy (IORT) has advantages in the treatment of patients with locally advanced pancreatic cancer (LAPC) compared with concurrent chemoradiotherapy (CCRT). PATIENTS AND METHODS: A total of 103 patients with LAPC whom was treated with IORT (Arm A; n = 50) or CCRT (Arm B; n = 53) from 2015.6 to 2016.7 were retrospectively identified. Data on feasibility, toxicity, and overall survival (OS) were evaluated. RESULTS: Most factors of the two cohorts were similar. The severe adverse events (grade 3 and 4) patients in Arm B were higher than patients in Arm A (34% vs 0%). Disease progression was noted in 38 patients (76%) in Arm A and 37 patients (69.8%) in Arm B. The median survival of patients in Arm A and B were 15.3 months (95% CI, 13.0-17.6 months) and 13.8 months (95% CI, 11.0-16.6 months), respectively. The 1-year survival rate were 66.3% in Arm A (95% CI, 52.3%-80.2%) and 60.9% in Arm B (95% CI, 46.4%-75.4%). There was no significant difference in OS between patients treated with IORT and with CCRT (p = 0.458). CONCLUSION: Our results demonstrated that patients with LAPC treated with IORT showed fewer adverse events, less treatment time, and high feasibility compared to CCRT. Although, IORT has no advantages in survival and tumor control compared with CCRT.

Combination of preoperative fibrinogen and D-dimer as a prognostic indicator in pancreatic ductal adenocarcinoma patients undergoing R0 resection.

BACKGROUND: Patients with malignant tumors frequently exhibit hyperactivation of the coagulation system and secondary increased fibrinolytic activity. Fibrinogen and D-dimer are common indicators that are crucial in the coagulation/fibrinolysis system. Both indicators have been verified to have predictive value in the overall survival (OS) of many patients with solid malignancies. AIM: To explore the prognostic significance of fibrinogen combined with D-dimer in pancreatic ductal adenocarcinoma (PDAC) patients undergoing radical R0 resection. METHODS: We retrospectively analyzed the clinical data of 282 patients with PDAC undergoing radical R0 resection in the Cancer Hospital, Chinese Academy of Medical Sciences, between January 2010 and December 2019. The surv_cutpoint function of R language was used to determine the optimal cutoff values of the preoperative fibrinogen concentration and preoperative D-dimer concentration. Enrolled patients were further divided into the any-high group (high preoperative fibrinogen concentration and/or high preoperative D-dimer concentration) and the low-low group (low preoperative fibrinogen and D-dimer concentrations) according to the optimal cutoff values. RESULTS: The optimal cutoff values of the preoperative fibrinogen concentration and preoperative D-dimer concentration were 3.31 g/L and 0.53 mg/L, respectively. Furthermore, multivariate Cox regression analysis showed that the preoperative fibrinogen concentration (HR: 1.603, 95%CI: 1.201-2.140, P = 0.001) and preoperative D-dimer concentration (HR: 1.355, 95%CI: 1.019-1.801, P = 0.036) exhibited obvious correlations with the OS of PDAC patients undergoing radical R0 resection. A prognostic analysis was further performed based on the subgroup results by using fibrinogen combined with D-dimer. The median OS duration of the low-low group (31.17 mo) was significantly longer than that of the any-high group (15.43 mo). Additionally, multivariate Cox regression analysis revealed that the degree of differentiation (P < 0.001), lymph node metastasis (HR: 0.663, 95%CI: 0.497-0.883, P = 0.005), preoperative CA19-9 level (HR: 1.699, 95%CI: 1.258-2.293, P = 0.001), adjuvant therapy (HR: 1.582, 95%CI: 1.202-2.081, P = 0.001) and preoperative combined grouping (HR: 2.397, 95%CI: 1.723-3.335, P < 0.001) were independent predictors of OS in PDAC patients undergoing radical R0 resection. CONCLUSION: Preoperative fibrinogen combined with D-dimer plays a predictive role in OS, and low preoperative fibrinogen and D-dimer concentrations can indicate prolonged OS in PDAC patients undergoing radical R0 resection.

Prognostic value of the preoperative fibrinogen-to-albumin ratio in pancreatic ductal adenocarcinoma patients undergoing R0 resection.

BACKGROUND: Inflammation plays an important role in tumor progression, and growing evidence has confirmed that the fibrinogen-to-albumin ratio (FAR) is an important prognostic factor for overall survival in malignant tumors. AIM: To investigate the prognostic significance of FAR in patients undergoing radical R0 resection of pancreatic ductal adenocarcinoma (PDAC). METHODS: We retrospectively analyzed the data of 282 patients with PDAC who underwent radical R0 resection at The Cancer Hospital of the Chinese Academy of Medical Sciences from January 2010 to December 2019. The surv_cutpoint function of the R package survminer via RStudio software (version 1.3.1073, http://www.rstudio.org) was used to determine the optimal cut-off values of biological markers, such as preoperative FAR. The Kaplan-Meier method and log-rank tests were used for univariate survival analysis, and a Cox regression model was used for multivariate survival analysis for PDAC patients who underwent radical R0 resection. RESULTS: The optimal cut-off value of FAR was 0.08 by the surv_cutpoint function. Higher preoperative FAR was significantly correlated with clinical symptoms (P = 0.001), tumor location (P < 0.001), surgical approaches (P < 0.001), preoperative plasma fibrinogen concentration (P < 0.001), and preoperative plasma albumin level (P < 0.001). Multivariate analysis showed that degree of tumor differentiation (P < 0.001), number of metastatic lymph nodes [hazard ratio (HR): 0.678, 95% confidence interval (CI): 0.509-0.904, P = 0.008], adjuvant therapy (HR: 1.604, 95%CI: 1.214-2.118, P = 0.001), preoperative cancer antigen 19-9 level (HR: 1.740, 95%CI: 1.288-2.352, P < 0.001), and preoperative FAR (HR: 2.258, 95%CI: 1.720-2.963, P < 0.001) were independent risk factors for poor prognosis in patients with PDAC who underwent radical R0 resection. CONCLUSION: The increase in preoperative FAR was significantly related to poor prognosis in patients undergoing radical R0 resection for PDAC. Preoperative FAR can be used clinically to predict the prognosis of PDAC patients undergoing radical R0 resection.

Equipping the American Joint Committee on Cancer Staging for Resectable Pancreatic Ductal Adenocarcinoma with Tumor Grade: A Novel Staging System.

BACKGROUND: The 8th American Joint Committee on Cancer (AJCC) staging system for pancreatic ductal adenocarcinoma (PDAC) outperforms its previous version in reproducibility but not in survival discrimination. Tumor grade, an indicator of the aggressive biology of PDAC, has been suggested as a reliable prognostic factor. This study aimed to construct a novel staging system with greater prognostication for resectable PDAC by incorporating tumor grade into the 8th AJCC system. METHODS: A total of 9966 patients with resectable PDAC from the Surveillance Epidemiology and End Results (SEER) database were randomly separated into training and interval validation sets. Another 324 patients from our center were included as an external validation set. We proposed a novel staging system by sorting the substages yielded by a combination of T, N, and tumor grade based on their overall survival (OS) and grouping them into several stages. Prognostic homogeneity and discrimination were determined using the likelihood ratio χ 2 and the linear trend χ 2 test, respectively. Prognostic accuracies were evaluated by the area under the receiver operating characteristics curve (AUC). RESULTS: Using the 8th AJCC system, the prognosis of patients within the same stage was quite heterogeneous among different substages. The multivariate Cox model identified the tumor grade (hazard ratio 1.333, 95% confidence interval 1.250-1.423, p < 0.001) was an independent prognostic factor of the OS. In the training set, the AUC, homogeneity, and discriminatory ability were superior for the novel staging system than for the 8th AJCC system (0.642 vs. 0.615, 403.4 vs. 248.6, and 335.1 vs. 218.0, respectively). Similar results were observed in the internal and external validation sets. CONCLUSIONS: The novel staging system incorporating tumor grade into the 8th AJCC system was associated with better prognostic accuracy, homogeneity, and discriminatory ability among resectable PDAC patients. Moreover, the novel staging system also allowed possibly adjuvant chemotherapy decisions.

Development and validation of a novel nomogram for predicting the prognosis of patients with resected pancreatic adenocarcinoma.

The survival prediction for patients with resected pancreatic adenocarcinoma by using the Tumor-Node-Metastasis (TNM) staging system remains limited. A nomogram is a efficient tool that can be used to predict the outcome of patients with various types of malignancy. The present study aimed to develop and validate a nomogram for patients with resected pancreatic adenocarcinoma. A total of 368 patients (258 in the training set and 110 in the validation set) who underwent pancreatic adenocarcinoma resection at the China National Cancer Center between January 2008 and October 2018 were included in the present study. The nomogram was established according to the results from Cox multivariate analysis, which was validated by discrimination and calibration. The area under the receiver operating characteristic curve (AUC) was determined to assess the accuracy of survival predictions. The results from multivariate analysis in the training set demonstrated that blood transfusion, T-stage, N-stage, tumor grade, capsule invasion, carbohydrate antigen 199, neutrophil percentage and adjuvant therapy were independent prognostic factors for overall survival (OS; all P<0.05). Subsequently, a nomogram predicting the 1-year, 3-year and 5-year OS rates, with favorable calibration, was established based on the independent prognostic factors. The concordance indices of the nomogram were higher compared with the TNM staging system in both training and validation sets. Furthermore, a clear risk stratification system based on the nomogram was used to classify patients into the three following groups: Low-risk group (≤168), moderate-risk group (168-255) and high-risk group (>255). The risk stratification system demonstrated an improved ability in predicting the 1-year, 3-year and 5-year OS rates compared with the TNM system (AUC, 0.758, 0.709 and 0.672 vs. AUC, 0.614, 0.604 and 0.568; all P<0.05). The present study developed and validated a nomogram for patients with resected pancreatic adenocarcinoma by including additional independent prognostic factors, including tumor marker, immune index, surgical information, pathological data and adjuvant therapy. Taken together, the results from the present study indicated an improved performance of the nomogram in predicting the prognosis of patients with resected pancreatic adenocarcinoma compared with the TNM staging system.

Elderly patients had more severe postoperative complications after pancreatic resection: A retrospective analysis of 727 patients.

AIM: To examine the impact of aging on the short-term outcomes following pancreatic resection (PR) in elderly patients. METHODS: A retrospective cohort study using prospectively collected data was conducted at the China National Cancer Center. Consecutive patients who underwent PR from January 2004 to December 2015 were identified and included. 'Elderly patient' was defined as ones age 65 and above. Comorbidities, clinicopathology, perioperative variables, and postoperative morbidity and mortality were compared between the elderly and young patients. Univariate and multivariate analyses were performed using the Cox proportional hazard model for severe postoperative complications (grades IIIb-V). RESULTS: A total of 454 (63.4%) patients were < 65-years-old and 273 (36.6%) patients were ≥ 65-years-old, respectively. Compared to patients < 65-years-old, elderly patients had worse American Society of Anesthesiologists scores (P = 0.007) and more comorbidities (62.6% vs 32.4%, P < 0.001). Elderly patients had more severe postoperative complications (16.8% vs 9.0%, P = 0.002) and higher postoperative mortality rates (5.5% vs 0.9%, P < 0.001). In the multivariate Cox proportional hazards model for severe postoperative complications, age ≥ 65 years [hazard ratio (HR) = 1.63; 95% confidence interval (CI): 1.18-6.30], body mass index ≥ 24 kg/m2 (HR = 1.20, 95%CI: 1.07-5.89), pancreaticoduodenectomy (HR = 4.86, 95%CI: 1.20-8.31) and length of operation ≥ 241 min (HR = 2.97; 95%CI: 1.04-6.14) were significant (P = 0.010, P = 0.041, P = 0.017 and P = 0.012, respectively). CONCLUSION: We found that aging is an independent risk factor for severe postoperative complications after PR. Our results might contribute to more informed decision-making for elderly patients.

Body mass index does not affect the survival of pancreatic cancer patients.

AIM: To evaluate the association of body mass index (BMI) with the overall survival of pancreatic ductal adenocarcinoma (PDAC) patients. METHODS: A retrospective analysis of PDAC patients diagnosed in the National Cancer Center of China between January 1999 and December 2014 was performed. These patients were categorized into four BMI groups (< 18.5, 18.5-22.9, 23-27.4 and ≥ 27.5 kg/m2). χ2 tests for comparison of the proportions of categorical variables, and Student's t-test or Mann-Whitney test for continuous variables were employed. Survival analysis was performed with the Kaplan-Meyer method. Their HRs of mortality and 95%CIs were estimated using the Cox proportional hazards model. RESULTS: With a median age of 59.6 years (range: 22.5-84.6 years), in total 1783 PDAC patients were enrolled in this study. Their mean usual BMI was 24.19 ± 3.53 for the whole cohort. More than half of the patients (59.3%) experienced weight loss during the disease onset and progression. Compared with healthy-weight individuals, newly diagnosed patients who were overweight or obese had more severe weight loss during their disease onset and progression (P < 0.001). Individuals who were overweight or obese were associated with positive smoking history (P < 0.001). A significant difference in comorbidity of diabetes (P = 0.044) and coronary artery disease (P < 0.001) was identified between high BMI and normal-weight patients. After a median follow-up of 8 mo, the survival analysis showed no association between BMI and the overall survival (P = 0.90, n = 1783). When we stratified the whole cohort by pancreatic cancer stage, no statistically significant association between BMI and overall survival was found for resectable (P = 0.99, n = 217), unresectable locally advanced (P = 0.90, n = 316) and metastatic patients (P = 0.88, n = 1250), respectively. The results did not change when we used the BMI at diagnosis. CONCLUSION: Our results showed no significance of BMI for the overall survival of PDAC patients.

Prognostic Factors and Clinical Characteristics of Patients with Primary Duodenal Adenocarcinoma: A Single-Center Experience from China.

Aim. To evaluate the clinical risk factors influencing overall survival of patients with duodenal adenocarcinoma after potentially curative resection. Methods. A series of 201 patients with primary duodenal adenocarcinoma who underwent surgery from 1999 to 2014 at Chinese Medical Academic Cancer Hospital were studied by retrospective chart review and subsequent telephone follow-up. Results. Resectional surgery was performed in 138 of the 201 patients to attempt curative treatment, while 63 patients were treated with palliative surgery. Median survival of patients who underwent resectional operation was 57 months, whereas that of patients who had palliative surgery was shorter, 7 months (p < 0.001). For patients who underwent radical resection, the overall 1-, 3-, and 5-year survival rates were 87.3, 59.1, and 44.1%, respectively. Multivariate Cox regression analysis revealed that lymph node metastasis (HR 31.76, 2.14 to 470.8; p = 0.012) and vascular invasion (HR 3.75, 1.24 to 11.38; p = 0.020) were independent prognostic factors negatively associated with survival in patients undergoing curative resection. There was no survival difference between the groups treated by the pancreaticoduodenectomy (n = 20) and limited resection (n = 10) for early-stage duodenal adenocarcinoma (p = 0.704). Conclusions. Duodenal adenocarcinoma is a rare disease. Curative resection is the best treatment for appropriate patients. Lymph node metastases and vascular invasion are negative prognostic factors.

Resection of the main trunk of the superior mesenteric vein without reconstruction during surgery for giant pancreatic mucinous cystadenoma: A case report.

Pancreatic tumors, with peri-pancreatic main vascular invasion, especially the superior mesenteric vein (SMV) or the portal vein, are very common. In some cases, vascular resection and reconstruction are required for complete resection of pancreatic tumors. However, the optimum surgical method for venous management is controversial. Resection of the SMV without reconstruction during surgery for pancreatic tumors is rarely reported. Here we present the case of a 58-year-old woman with a giant pancreatic mucinous cystadenoma adhering to the SMV, who underwent an en bloc tumor resection, including the main trunk of the SMV and the spleen. No venous reconstruction was performed during surgery. No ischemic changes occurred in the bowel. The presence of several well-developed collateral vessels was shown by 3-dimensional computed tomography examination. The patient had an uneventful postoperative period and was discharged. This case indicated that the main trunk of the SMV can be resected without venous reconstruction if adequate collateralization has formed.

Impact of body mass index on complications following pancreatectomy: Ten-year experience at National Cancer Center in China.

AIM: To examine the impact of body mass index (BMI) on outcomes following pancreatic resection in the Chinese population. METHODS: A retrospective cohort study using prospectively collected data was conducted at the Cancer Hospital of the Chinese Academy of Medical Sciences, China National Cancer Center. Individuals who underwent pancreatic resection between January 2004 and December 2013 were identified and included in the study. Persons were classified as having a normal weight if their BMI was < 24 kg/m(2) and overweight/obese if their BMI was ≥ 24 kg/m(2) as defined by the International Life Sciences Institute Focal Point in China. A χ(2) test (for categorical variables) or a t test (for continuous variables) was used to examine the differences in patients' characteristics between normal weight and overweight/obese groups. Multiple logistic regression models were used to assess the associations of postoperative complications, operative difficulty, length of hospital stay, and cost with BMI, adjusting for age, sex, and type of surgery procedures. RESULTS: A total of 362 consecutive patients with data available for BMI calculation underwent pancreatic resection for benign or malignant disease from January 1, 2004 to December 31, 2013. Of the 362 patients, 156 were overweight or obese and 206 were of normal weight. One or more postoperative complications occurred in 35.4% of the patients following pancreatic resection. Among patients who were overweight or obese, 42.9% experienced one or more complications, significantly higher than normal weight (29.6%) individuals (P = 0.0086). Compared with individuals who had normal weight, those with a BMI ≥ 24.0 kg/m(2) had higher delayed gastric emptying (19.9% vs 5.8%, P < 0.0001) and bile leak (7.7% vs 1.9%, P = 0.0068). There were no significant differences seen in pancreatic fistula, gastrointestinal hemorrhage, reoperation, readmission, or other complications. BMI did not show a significant association with intraoperative blood loss, operative time, length of hospital stay, or cost. CONCLUSION: Higher BMI increases the risk for postoperative complications after pancreatectomy in the Chinese population. The findings require replication in future studies with larger sample sizes.

Correlation between metastatic lymph node ratio and prognosis in patients with extrahepatic cholangiocarcinoma.

AIM: To investigate the prognostic value of metastatic lymph node ratio (MLNR) in extrahepatic cholangiocarcinoma (ECC) patients undergoing radical resection. METHODS: Seventy-eight patients with ECC were enrolled. Associations between various clinicopathologic factors and prognosis were investigated by Kaplan-Meier analyses. The Cox proportional-hazards model was used for multivariate survival analysis. RESULTS: The overall three- and five-year survival rates were 47.26% and 23.99%, respectively. MLNR of 0, 0-0.2, 0.2-0.5, and > 0.5 corresponded to five-year survival rates of 28.59%, 21.60%, 18.84%, and 10.03%, respectively. Univariate analysis showed that degree of tumor differentiation, lymph node metastasis, MLNR, tumor-node-metastasis (TNM) stage, and margin status were closely associated with postoperative survival in ECC patients (P < 0.05). Multivariate analysis showed that MLNR and TNM stage were independent prognostic factors after pancreaticoduodenectomy (HR = 2.13, 95%CI: 1.45-3.11; P < 0.01; and HR = 1.97, 95%CI: 1.17-3.31; P = 0.01, respectively). The median survival time for MLNR > 0.5, 0.2-0.5, 0-0.2, and 0 was 15 mo, 24 mo, 23 mo, and 35.5 mo, respectively. There were statistical differences in survival time between patients with different MLNR (χ(2) = 15.38; P < 0.01). CONCLUSION: MLNR is an independent prognostic factor for ECC patients after radical resection and is useful for predicting postoperative survival.

Early plasma exchange for treating ricin toxicity in children after castor bean ingestion.

Plasma exchange (PE) for the treatment of ricin toxicity has not been previously reported. Here we describe the use of PE to treat children who experienced ricin toxicity after ingesting castor beans. Seven children (median age: 8.1 years) who consumed castor beans (median: 5 beans) were treated with PE. All had bradycardia and sinus arrhythmia, and most had experienced episodes of vomiting and/or diarrhea. PE settings were blood flow, 50-80 mL/min; PE rate, 600-800 mL/h; volume of exchange, 1440-1950 mL. Median time from ingestion to PE was 73 h. All clinical symptoms disappeared and vital signs rapidly returned to normal after PE; no severe organ dysfunction occurred. All children were discharged and recovered uneventfully. Concentrations of all serum biochemical parameters significantly decreased immediately after PE. Some, but not all, of these parameters were also significantly decreased at 48 and 72 h after PE compared with before PE. Our findings suggest that PE can be an effective early intervention in the treatment of ricin toxicity due to castor bean ingestion.

Identification of genomic alterations in pancreatic cancer using array-based comparative genomic hybridization.

BACKGROUND: Genomic aberration is a common feature of human cancers and also is one of the basic mechanisms that lead to overexpression of oncogenes and underexpression of tumor suppressor genes. Our study aims to identify frequent genomic changes in pancreatic cancer. MATERIALS AND METHODS: We used array comparative genomic hybridization (array CGH) to identify recurrent genomic alterations and validated the protein expression of selected genes by immunohistochemistry. RESULTS: Sixteen gains and thirty-two losses occurred in more than 30% and 60% of the tumors, respectively. High-level amplifications at 7q21.3-q22.1 and 19q13.2 and homozygous deletions at 1p33-p32.3, 1p22.1, 1q22, 3q27.2, 6p22.3, 6p21.31, 12q13.2, 17p13.2, 17q21.31 and 22q13.1 were identified. Especially, amplification of AKT2 was detected in two carcinomas and homozygous deletion of CDKN2C in other two cases. In 15 independent validation samples, we found that AKT2 (19q13.2) and MCM7 (7q22.1) were amplified in 6 and 9 cases, and CAMTA2 (17p13.2) and PFN1 (17p13.2) were homozygously deleted in 3 and 1 cases. AKT2 and MCM7 were overexpressed, and CAMTA2 and PFN1 were underexpressed in pancreatic cancer tissues than in morphologically normal operative margin tissues. Both GISTIC and Genomic Workbench software identified 22q13.1 containing APOBEC3A and APOBEC3B as the only homozygous deletion region. And the expression levels of APOBEC3A and APOBEC3B were significantly lower in tumor tissues than in morphologically normal operative margin tissues. Further validation showed that overexpression of PSCA was significantly associated with lymph node metastasis, and overexpression of HMGA2 was significantly associated with invasive depth of pancreatic cancer. CONCLUSION: These recurrent genomic changes may be useful for revealing the mechanism of pancreatic carcinogenesis and providing candidate biomarkers.

Clearance of serum solutes by hemofiltration in dogs with severe heat stroke.

BACKGROUND: We have previously reported that hemofiltration (HF) may be an effective additional means of treating heat stroke when rapid cooling is not effective. METHODS: Dogs were assigned to a heat stroke (control) or heat stroke + hemofiltration (HF) group (n = 8 each group). After heat stroke induction, dogs in the HF group received HF for 3 h. Serum concentrations of interleukin (IL)-10, tumor necrosis factor (TNF)-α, IL-6, blood urea nitrogen (BUN) and creatinine were measured at baseline and 1, 2, and 3 h after heat stroke. Clearance rates of solutes were determined 1, 2, and 3 h after the start of HF. RESULTS: Serum concentrations of all solutes tended to increase with time after heat stroke in the control group, but decreased (BUN, creatinine) or remained relatively unchanged (TNF-α, IL-6, IL-10) with time in the HF group. Concentrations of all solutes were significantly lower in the HF group compared with the control group at 2 and 3 h (P < 0.05). Clearance rates for small molecular weight solutes were high, while those for larger molecular weight solutes were low. CONCLUSION: HF prevents heat stroke-induced increases in serum cytokine concentrations and is effective for clearing small molecular weight solutes from serum, but less effective for clearing larger molecular weight solutes, including TNF-α, IL-6, and IL-10.

[Mutational analysis of MYO1E in Chinese children with familial steroid-resistant nephrotic syndrome].

OBJECTIVE: Steroid-resistant nephrotic syndrome (SRNS) with MYO1E mutations has been identified as autosomal recessive focal segmental glomerulosclerosis (FSGS). To date, only two homozygous mutations in the MYO1E gene were reported in three families with FSGS. This study aimed to examine mutations in the MYO1E gene in children with familial SRNS in the Han Chinese ethnic group. METHODS: Between 2005 and 2010, peripheral blood samples were collected from the probands, their siblings and parents of four families with autosomal recessive SRNS in the Han Chinese ethnic group. Four probands were studied from nine patients. The mutational analysis of MYO1E was performed by polymerase chain reaction and direct DNA sequencing. Fifty-nine healthy volunteers with normal urine analysis were included as controls. RESULTS: Twenty-five MYO1E variants in the prohands from 4 families with SRNS were identified in this study. Among them, 24 variants were found in NCBI dbSNP. One heterozygous mutation IVS21-85G>A was found in the prohand from Family D, whereas it was absent in 59 normal Chinese controls. No splice site change caused by IVS21-85G>A was reported by analysis with NetGene2. CONCLUSIONS: MYO1E mutations are not a major cause of Chinese familial SRNS in this study.

Tumors of the angle of Treitz: a single-center experience.

AIM: To explore the feasibility and oncologic outcomes of segmental jejunal resection on the left side of the mesenteric vessels in patients with tumors of the angle of Treitz using data from a single center. METHODS: Thirteen patients with tumors of the angle of Treitz who underwent surgery at our institution were prospectively followed. A segmental jejunal resection on the left side of the mesenteric vessels was performed in all patients. Formalin-fixed and paraffin-embedded tumor samples were examined. The primary end point of this analysis was disease-free survival. RESULTS: In this study, there were 8 males and 5 females (mean age, 50.1 years; range, 36-74 years). The mean tumor size was 8.1 cm (range, 3.2-15 cm). Histologic examination showed 11 gastrointestinal stromal tumors (GISTs) and 2 adenocarcinomas. Five of the GIST patients presented with potential low risk, and 6 presented with intermediate and high risk, according to the National Institutes of Health criteria. One potentially high-risk patient showed tumor progression at 46 mo and died 52 mo after surgery. One patient with locally advanced adenocarcinoma received neoadjuvant chemotherapy and adjuvant radiotherapy, but the disease progressed, and the patient died 9 mo after surgery. One GIST patient without progression died 16 mo after surgery because of a postoperative intestinal obstruction. The median overall survival rate was 84.6 mo, and the median disease-free survival rate was 94.5 mo. CONCLUSION: The overall survival of patients with tumors of the angle of Treitz was encouraging even when the tumor size was relatively large. A segmental resection on the left side of the mesenteric vessels is considered to be a reliable and curative option for tumors of the angle of Treitz.