Adenocarcinoma developing from gastric heterotopic pancreas: a case report and short review.

Heterotopic pancreas is a relatively rare condition that may be associated to clinical complaints or signs. Here, we report a case of gastric heterotopic pancreas assictaed to ductal adenocarcinoma. Obstructive jaundice was the initial symptom prompting medical intervention. A 73-year-old male patient presented with yellow staining of the skin and sclera, and dull epigastric pain. Contrast-enhanced computed tomography showed stenosis of the extrahepatic distal bile duct and mass lesions of the antrum. The patient underwent tumor resection, distal gastrectomy (Billroth II), and common bile duct exploration. Postoperative pathological examination revealed an adenocarcinoma located in the wall of the gastric antrum. Immunohistochemical results suggested that the tumor originated from the pancreas. Heterologous pancreatic tissue and a dilated pancreatic duct were found in the tumor. These findings suggest malignant transformation of the gastric heterotopic pancreas. Of note, jaundice as clinical complaint for adenocarcinoma associated to gastric heterotopic pancreas.

Cost-Effectiveness of First-Line Atezolizumab versus Chemotherapy in Non-Small-Cell Lung Cancer Patients Ineligible for Platinum-Containing Regimens.

Purpose: The IPSOS study provided evidence supporting the efficacy and tolerability of first-line atezolizumab compared to single-agent chemotherapy for non-small-cell lung cancer (NSCLC) patients ineligible for treatment with a platinum-containing regimen. This study aimed to assess the cost-effectiveness of atezolizumab specifically in this population, considering the perspective of the Chinese healthcare system. Patients and Methods: In this analysis, a three-state Markov model was utilized. The survival data were derived from the IPSOS clinical trial. Direct medical costs and utility values were collected from national authoritative database and published literature. The primary outcomes were costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER). To ensure the robustness of our model, both one-way and probabilistic sensitivity analyses were conducted. Results: Atezolizumab monotherapy led to an increase in costs of $4139.23 compared to single-agent chemotherapy. Additionally, it resulted in a gain of 0.14 QALYs, leading to an ICER of $29,365.79 per QALY, which was below the willingness-to-pay threshold of $36,066 per QALY used in the model. One-way sensitivity analyses revealed cost of atezolizumab and utility of progressive disease (PD) as major influencing factors for ICER. Furthermore, probabilistic sensitivity analyses confirmed our base-case results. Conclusion: From the perspective of the Chinese healthcare system, atezolizumab emerges as a cost-effective choice for the first-line treatment of NSCLC patients ineligible for platinum-based chemotherapy.

SERPINB5 is a novel serum diagnostic biomarker for gastric high-grade intraepithelial neoplasia and plays a role in regulation of macrophage phenotypes.

BACKGROUND: Gastric cancer (GC) develops from gastric precancerous lesions (GPL), and early diagnosis and treatment at the premalignant stage may achieve a higher benefit‒cost ratio with a reduced necessity for surgery. However, reliable noninvasive screening biomarkers of GPL are currently lacking. METHODS: The marker genes of GPL encoding extracellular proteins were identified by bioinformatics analysis and further verified by immunofluorescence and immunohistochemistry assays. Serum samples were collected to measure the levels of SERPINB5, the diagnostic efficacy of which was assessed by the area under the receiver operating characteristic (ROC) curve (AUC). Finally, the effect of SERPINB5 on the phenotypic conversion of macrophages was verified by public data and in vitro experiments. RESULTS: SERPINB5 was identified as an extracellular biomarker of GPL that had good diagnostic efficacy. High expression of SERPINB5 was observed in the epithelial cells and adjacent extracellular matrix on sections of gastric high-grade intraepithelial neoplasia (HGIN). Importantly, SERPINB5 determined in serum was significantly increased in the HGIN group, and the AUC for discriminating between HGIN and chronic gastritis or low-grade intraepithelial neoplasia was 0.9936 and 0.9750, respectively. Moreover, SERPINB5 expression was positively correlated with macrophage infiltration, and M1 marker NOS2 expression, but negatively correlated with M2 marker CSF1R expression. In THP-1-derived macrophages, SERPINB5 upregulated expression of M1-related cytokines TNF-α and IL-12, and M1 marker CD86, but suppressed production of M2-related cytokines TGF-ß and IL-10. CONCLUSIONS: Our study provides evidence that SERPINB5 may serve as a promising noninvasive serum biomarker for gastric HGIN screening and regulate macrophage phenotype conversion.

The efficacy and safety of first­line anti­PD­1/PD­L1 immunotherapy for gastric esophageal cancer: A systematic review and meta­analysis of phase III randomized controlled trials.

Immunotherapy-based regiments have potential as first-line treatment for advanced gastric esophageal cancer. The present study aimed to conduct a meta-analysis of the association between the efficacy and safety of first-line immunotherapy combined with chemotherapy in patients with unresectable locally advanced or metastatic gastric esophageal cancer. Subgroup analysis of patients with programmed death ligand 1 (PD-L1) combined positive score (CPS) was conducted to identify the characteristics of patients with immune benefit and to provide a decision-making basis for clinical practice. PubMed, Embase, Cochrane Library and other databases were searched to collect randomized controlled trials of immunotreatment-based regimens (experimental group) versus conventional first-line chemotherapy regimens (control group) for unresectable locally advanced or metastatic gastric esophageal cancer. The main outcome measures included progression-free survival (PFS), overall survival (OS), objective response rate, disease control rate and safety, and the secondary outcomes were the differences in OS and PFS between patients with PD-L1 CPS ≥10 and those with PD-L1 CPS <10. In addition, Asian and non-Asian populations were analysed. Nine studies with a total of 6,820 patients were included. The OS of patients treated with immunotherapy-based regimens was significantly longer than that of those treated with chemotherapy alone [HR=0.74; 95% CI (0.69, 0.80); P<0.00001]. The OS of patients with PD-L1 CPS ≥10 and PD-L1 CPS <10 in the experimental group was significantly longer than that of patients in the control group [HR=0.68; 95% CI (0.59, 0.77); P<0.00001 and HR=0.73; 95% CI (0.62, 0.87); P=0.0005]. The PFS of patients being treated with immunotherapy-based regimens was significantly longer than that of those treated with chemotherapy alone [HR=0.71; 95% CI (0.59, 0.86); P=0.0003]. In addition, the PFS of patients with PD-L1 CPS ≥10 and PD-L1 CPS <10 in the experimental group was significantly longer than that of patients in the control group [HR=0.67; 95% CI (0.49, 0.92); P=0.01 and HR=0.63; 95% CI (0.48, 0.83); P=0.001]. There was no significant difference in the overall incidence of adverse events and the incidence of grade 3 or above adverse events between the experimental and control groups [RR=1; 95% CI (0.99, 1.02); P=0.65 and RR=0.97; 95% CI (0.84, 1.12); P=0.69, respectively]. In conclusion, treatment with immunotherapy-based regimens may prolong the OS of patients with unresectable locally advanced or metastatic gastric esophageal cancer and this treatment regimen is safe compared with chemotherapy alone.

Relationship between postoperative biliary stricture and clinical characteristics of patients with benign and malignant biliary diseases.

Introduction: Postoperative biliary stricture (POBS) is one of the common complications of biliary surgery. Previous literature on risk factors of POBS was scarce, and the classification of POBS in benign and malignant biliary diseases was incomplete. Aim: To analyze clinicopathological factors of POBS in usual biliary diseases, and to facilitate preoperative diagnosis of biliary stricture. Material and methods: A retrospective analysis was made on the clinical data of 2228 patients who underwent biliary surgery in our hospital from July 2010 to June 2022. With the inclusion and exclusion criteria, the clinicopathological factors for POBS were classified, and data analysis was conducted. Results: Benign diseases with age ≥ 60 years (p = 0.034), diabetes (p = 0.001), common bile duct diameter < 0.8 cm (p = 0.034), Mirizzi syndrome (p = 0.001), seniority of surgeons < 25 years (p = 0.001), and operation time for the first 6 years (p = 0.015) are more likely to evolve into POBS; malignant diseases with conjugated bilirubin ≥ 6.8 µmol/l (p = 0.042), alkaline phosphatase ≥ 125 U/l (p = 0.042), γ-glutamyl transferase ≥ 50 U/l (p = 0.047), diabetes (p = 0.038), and seniority of surgeons < 25 years (p = 0.008) are prone to POBS. Different surgical approaches affect the incidence of POBS (χ2 = 9.717, p = 0.034). The choice of surgical site is important for the incidence of POBS in malignant diseases (χ2 = 7.935, p = 0.041). Conclusions: Surgeons need to identify risk factors, conduct patient visits and assessments preoperatively, standardize the operation in order to avoid structural damage, and reduce the occurrence of POBS.

Cancer-associated fibroblasts suppress ferroptosis and induce gemcitabine resistance in pancreatic cancer cells by secreting exosome-derived ACSL4-targeting miRNAs.

BACKGROUND: Pancreatic cancer continues to be one of the world's most lethal cancers. Chemotherapy resistance in patients with advanced pancreatic cancer often accompany with dismal prognosis, highlighting the need to investigate mechanisms of drug resistance and develop therapies to overcome chemoresistance. METHODS: This research was filed with the Chinese Clinical Trial Registry (ChiCTR2200061320). In order to isolate primary normal fibroblasts (NFs) and cancer-associated fibroblasts (CAFs) samples of pancreatic ductal adenocarcinoma (PDAC) and paracancerous pancreatic tissue from individuals diagnosed with PDAC were obtained. The exosomes were obtained using ultracentrifugation, and their characteristics were determined by Western blotting, nanoparticle tracking analysis, and transmission electron microscopy. CAF-derived miRNAs were analyzed by RT-qPCR and high-throughput sequencing. Gemcitabine (GEM) was employed to promote ferroptosis, and ferroptosis levels were determined by monitoring lipid reactive oxygen species (ROS), cell survival, and intracellular Fe2+ concentrations. To assess in vivo tumor response to GEM therapy, a xenograft tumor mouse model was utilized. RESULTS: Exosomes derived from CAFs in PDAC did not exhibit innate GEM resistance. CAFs promoted chemoresistance in PDAC cells following GEM treatment by secreting exosomes, and maintaining signaling communication with cancer cells. Mechanistically, miR-3173-5p derived from CAF exosomes sponged ACSL4 and inhibited ferroptosis after uptake by cancer cells. CONCLUSION: This work demonstrates a novel mode of acquired chemoresistance in PDAC and identifies the miR-3173-5p/ACSL4 pathway as a promising treatment target for GEM-resistant pancreatic cancer.

Identification and validation of EMT-immune-related prognostic biomarkers CDKN2A, CMTM8 and ILK in colon cancer.

Colon cancer (CC) is a disease with high incidence and mortality rate. The interaction between epithelial-mesenchymal transition (EMT) and immune status has important clinical significance. We aim to identify EMT-immune-related prognostic biomarkers in colon cancer. The GEO2R and GEPIA 2.0 were utilized to calculate the differential expression genes between CC and normal mucosa. Immport, InnateDB and EMTome databases were used to define EMT-immune-related genes. We conducted batch prognostic analysis by TCGA data. The expression patterns were verified by multiple datasets and lab experiments. GEPIA 2.0 and TIMER 2.0 were utilized to analyze the correlation of the hub genes with EMT markers and immune infiltration. GeneMANIA, STRING, and Metascape were used for co-expression and pathway enrichment analysis. Finally, we established a signature by the method of multivariate Cox regression analysis. CDKN2A, CMTM8 and ILK were filtered out as prognostic genes. CDKN2A and CMTM8 were up-regulated, while ILK was down-regulated in CC. CDKN2A was positively correlated with infiltration of macrophages, Th2 cells, Treg cells, and negatively correlated with NK cells. CMTM8 was negatively correlated with CD8+ T cells, dendritic cells, and NK cells. ILK was positively correlated with CD8+ T cells and dendritic cells. Moreover, CDKN2A, CMTM8 and ILK were significantly correlated with EMT markers. The three genes could participate in the TGF-ß pathway. The prognosis model established by the three hub genes was an independent prognosis factor, which can better predict the prognosis. CDKN2A, CMTM8 and ILK are promising prognostic biomarkers and may be potential therapeutic targets in colon cancer.

REC8 enhances stemness and promotes metastasis of colorectal cancer through BTK/Akt/ß-catenin signaling pathway.

Cancer/testis antigens (CTAs) are often aberrantly expressed in cancer stem cells (CSCs) which are responsible for tumor metastasis. Rec8 meiotic recombination protein (REC8), a member of CTAs, shares distinct roles in various cancers, while its contribution to CSCs and colorectal cancer (CRC) remains unclear. We found that overexpression of REC8 facilitated the migration and invasion of CRC cells (DLD-1 and SW480 cells) in vitro and promoted the liver metastasis of CRC in vivo. Moreover, REC8 is highly expressed in CRC stem-like cells and is required for the maintenance of CSC stemness. Mechanistic studies suggested that REC8 mediated through the activation of Bruton tyrosine kinase (BTK). Inhibition of BTK by ibrutinib not only suppressed the migration and invasion-promoting ability, but also declined the increased expression of p-BTK, p-Akt, ß-catenin, and CSC markers upon REC8 overexpression. Importantly, high expression of REC8 in cancerous tissues was related to advanced clinical stage and lymph node metastasis of 62 CRC patients, and REC8 was enriched in the cancerous cells positive for CSC markers. Collectively, our results indicate that REC8 promotes CRC metastasis by increasing cell stemness through BTK/Akt/ß-catenin pathway.

The role of non-coding RNAs in ferroptosis regulation.

Ferroptosis is a newly recognized form of cell death that is distinct from apoptosis, necrosis, autophagy in morphology, biochemistry, and heredity. The basic process of ferroptosis involves disordered permeability of plasma membrane, which is caused by abnormal accumulation of lipids and reactive oxygen species (ROS). The regulatory mechanism of ferroptosis is important due to its involvement in tumor progression, neurotoxicity, neurodegenerative diseases, acute renal failure, and ischemia-reperfusion injury. Recent studies have shown that in ferroptosis metabolism, non-coding RNAs (ncRNAs) can interfere with multiple signaling pathways at both the pre-transcriptional and post-transcriptional levels. Despite great progress, current research on the mechanism of ncRNAs and ferroptosis remains insufficient. This review provides an overview of the main mechanisms and targets of ferroptosis and focuses on the mechanisms of non-coding RNA regulation. Analyzing the deficiencies in current research may provide ideas for future studies to investigate.

A FAK Inhibitor Boosts Anti-PD1 Immunotherapy in a Hepatocellular Carcinoma Mouse Model.

Anti-PD-1/PD-L1 immunotherapy has limited efficacy in hepatocellular carcinoma (HCC) and does not benefit all patients. A FAK inhibitor (VS-4718) has been reported to improve the microenvironment in some tumors. This study aimed to investigate the effect of the combination of the FAK inhibitor VS4718 and anti-PD1 for the treatment of HCC in a mouse model and its possible mechanism of action. The expression of FAK and infiltrated immune cells in human HCC from the data of TCGA were analyzed. A primary murine HCC model was established via protooncogene (c-Met/ß-catenin) transfection. The pathological characteristics of tumors were examined after the mice were treated with VS4718 and/or anti-PD1 therapy. This study revealed that FAK is highly expressed in human HCC and is associated with poor prognosis of OS (overall survival) and PFS (progress free survival) in HCC patients. Immune cell infiltration (CD8+ T, Tregs, M0, M2, CAFs and MDSCs) was correlated with FAK expression. In the experimental HCC model, the combination of a FAK inhibitor VS4718 and an anti-PD1 antibody had a better effect than monotherapy against HCC. VS4718 reduced the number of Tregs and macrophages but increased the number of CD8+ T cells in HCC mice. Notably, FAK inhibitor promoted the expression of PD-L1 in HCC. This study suggested that combination of the FAK inhibitor VS4718 and anti-PD1 could be a potential therapy for HCC by improving the immune environment, reducing liver fibrosis and simultaneously preventing PD1 from binding to the increased PD-L1 induced by FAK inhibitor VS4718.

Schisandrin B prevents ulcerative colitis and colitis-associated-cancer by activating focal adhesion kinase and influence on gut microbiota in an in vivo and in vitro model.

Colitis-associated cancer (CAC) has a close relationship with ulcerative colitis (UC). Therapeutic effect of Schisandrin B (SchB) on UC and CAC remains largely unknown. We investigated the preventative effect of SchB on the dextran sulphate sodium (DSS) model of UC and azoxymethane (AOM)/DSS model of CAC. Furthermore, focal adhesion kinase (FAK) activation and influence on commensal microbiota are important for UC treatment. Impact on FAK activation by SchB in UC development was evaluated in vivo and vitro. We also conducted 16S rRNA sequencing to detect regulation of gut microbiota by SchB. Enhanced protection of intestinal epithelial barrier by SchB through activating FAK contributed to protective effect on colon for the fact that protection of SchB can be reversed by inhibition of FAK phosphorylation. Furthermore, influence on gut microbiota by SchB also played a significant role in UC prevention. Our results revealed that SchB was potent to prevent UC by enhancing protection of intestinal epithelial barrier and influence on gut microbiota, which led to inhibition of CAC. SchB was potential to become a new treatment for UC and prevention of CAC.

Mild Hypothermia Prevents NO-Induced Cytotoxicity in Human Neuroblastoma Cells Via Induction of COX-2.

The cold-inducible protein RBM3 mediates hypothermic neuroprotection against nitric oxide (NO)-induced cell death. Meanwhile, it is well-known that cyclooxygenase-2 (COX-2) is upregulated by RBM3 in several types of cells; however, it is still unclear whether COX-2 contributes to the neuroprotective effects of mild hypothermia/RBM3 against NO-induced cell death. Using human SH-SY5Y neuroblastoma cells, it was revealed that NO remarkably downregulates the expression of COX-2 at both mRNA and protein levels. When COX-2 was silenced using siRNA technique, cells became more sensitive to NO-induced cell death. Conversely, the overexpression of COX-2 significantly prevented NO-induced cell death in SH-SY5Y cells, indicating a pro-survival role of COX-2. Upon mild hypothermia pre-treatment, COX-2 was notably induced at both mRNA and protein levels; however, COX-2 silencing abrogated hypothermia-related neuroprotection against NO-induced cell death. Furthermore, it was revealed that either silencing or overexpression of RBM3 had no effects on the expression of COX-2 in SH-SY5Y cells. These findings suggest that mild hypothermia could protect neuroblastoma cells against NO-induced cell death by inducing COX-2 in a RBM3-independent manner.

[Effects of carbon supplementary modes on phosphorus bioaccumulation/phosphorus harvesting process in a tidal flow constructed wetland.] / 碳源补å 方式对潮汐流人工湿地生物蓄磷/磷移除的影响.

We explored the effects of carbon supplementary modes on operational performance in a tidal flow constructed wetland (TFCW) utilizing phosphorus bioaccumulation/phosphorus harvesting (PB-PH) process. Three different carbon supplementary modes were adopted during the periodical phosphorus harvesting process. The results showed that the carbon supplementary mode significantly affected the performances of phosphorus bioaccumulation and phosphorus harvesting throughout the experiment. The optimization of carbon supplementary mode would facilitate the maintenance of abundance and activities of polyphosphate-accumulating organisms (PAOs). Subsequently, the amounts of phosphorus release and PHB synthesis in PAOs, as well as the utilization rate of supplementary carbon, could be effectively enhanced during the phosphorus harvesting process. The efficient and stable phosphorus removal effects of the TFCW could be ensured during the phosphorus bioaccumulation process. When the PB-PH cycle length was 30 d and using the continuous circulation carbon supplementary mode, the amount of phosphorus retained in the bed and the mean phosphorus harvesting efficiency of the TFCW were 26994.88 mg and 70.8%, respectively. Regarding a typical PB-PH cycle, the mean phosphorus removal efficiency of the TFCW could achieve (91.4±2.1)% during the phosphorus bioaccumulation process. The amounts of phosphorus release and PHB synthesis in PAOs, and the utilization rate of supplementary carbon in the system could reach up to (1563.72±127.84) mg, (4.52±0.39) mmol C·g-1 VSS, and (97.3±1.6)%, respectively.

Expression of inositol-requiring enzyme 1ß is downregulated in colorectal cancer.

The endoplasmic reticulum stress inositol-requiring enzyme (IRE) 1α/X-box binding protein (XBP) 1 signaling pathway is involved in the tumorigenesis of breast and prostate cancer. Mucin 2 (MUC2) protects colon tissues from the formation of tumors. In human colorectal cancer (CRC) the role of IRE1α, and its analogue, IRE1ß, has yet to be elucidated. In the present study, the expression levels of IRE1α, IRE1ß, un-spliced XBP1u, spliced XBP1s and MUC2 in surgically resected cancerous and adjacent non-cancerous tissues from patients with CRC were investigated. The IRE1α, IRE1ß, XBP1u, XBP1s and MUC2 mRNA expression levels were determined using reverse transcription-quantitative polymerase chain reaction, and the protein expression levels were detected using immunohistochemistry and western blotting. The association between the expression levels of IRE1α, IRE1ß and MUC2 and the clinicopathological features of patients with CRC was subsequently analyzed. The mRNA expression levels of IRE1ß and MUC2 were decreased by ~2.1 and ~4.5-fold in CRC tissues, respectively, as compared with the adjacent normal tissues. The protein expression levels of IRE1ß and MUC2 were decreased by ~8.0 and ~2.0-fold in the CRC tissues, respectively. IRE1ß mRNA expression levels were positively correlated with MUC2 mRNA expression levels. IRE1ß expression levels were revealed to be significantly associated with lymph node metastasis, tumor stage and histological differentiation. However, IRE1α, XBP1u and XBP1s mRNA and IRE1α protein expression levels were not observed to significantly differ between cancerous tissues and the adjacent normal tissues. The results indicated that the expression of IRE1ß, but not IRE1α, may protect colon tissue from developing CRC by inducing MUC2 expression. Therefore, decreased IRE1ß expression levels may be associated with the development of CRC through the inhibition of MUC2 expression.

DUOX2 Expression Is Increased in Barrett Esophagus and Cancerous Tissues of Stomach and Colon.

Aim. To detect the expression of dual oxidase (DUOX) 2 in Barrett esophagus, gastric cancer, and colorectal cancer (CRC). Materials and Methods. The endoscopic biopsies were collected from patients with Barrett esophagus, while the curative resection tissues were obtained from patients with gastric cancer, CRC, or hepatic carcinoma. The DUOX2 protein and mRNA levels were detected with immunohistochemistry (IHC) and real-time quantitative PCR (qPCR). The correlation of DUOX2 expression with clinicopathological parameters of tumors was identified. Results. Low levels of DUOX2 mRNA were detected in Barrett esophagus and the adjacent normal tissues, and there was no difference between these two groups. DUOX2 protein was found in Barrett esophagus and undetectable in the normal epithelium. The DUOX2 mRNA and protein levels in the gastric cancer and CRC were increased compared to the adjacent nonmalignant tissues. The elevated DUOX2 in the gastric cancer was significantly associated with smoking history. In CRC tissues, the DUOX2 protein expression level in stages II-IV was significantly higher than that in stage I. In both hepatic carcinoma and the adjacent nonmalignant tissue, the DUOX2 was virtually undetectable. Conclusion. DUOX2 in Barrett esophagus, gastric cancer, and CRC may be involved in the tumorigenesis of these tissues.

Cost Prediction Using a Survival Grouping Algorithm: An Application to Incident Prostate Cancer Cases.

BACKGROUND: Prognostic classification approaches are commonly used in clinical practice to predict health outcomes. However, there has been limited focus on use of the general approach for predicting costs. We applied a grouping algorithm designed for large-scale data sets and multiple prognostic factors to investigate whether it improves cost prediction among older Medicare beneficiaries diagnosed with prostate cancer. METHODS: We analysed the linked Surveillance, Epidemiology and End Results (SEER)-Medicare data, which included data from 2000 through 2009 for men diagnosed with incident prostate cancer between 2000 and 2007. We split the survival data into two data sets (D0 and D1) of equal size. We trained the classifier of the Grouping Algorithm for Cancer Data (GACD) on D0 and tested it on D1. The prognostic factors included cancer stage, age, race and performance status proxies. We calculated the average difference between observed D1 costs and predicted D1 costs at 5 years post-diagnosis with and without the GACD. RESULTS: The sample included 110,843 men with prostate cancer. The median age of the sample was 74 years, and 10% were African American. The average difference (mean absolute error [MAE]) per person between the real and predicted total 5-year cost was US$41,525 (MAE US$41,790; 95% confidence interval [CI] US$41,421-42,158) with the GACD and US$43,113 (MAE US$43,639; 95% CI US$43,062-44,217) without the GACD. The 5-year cost prediction without grouping resulted in a sample overestimate of US$79,544,508. CONCLUSION: The grouping algorithm developed for complex, large-scale data improves the prediction of 5-year costs. The prediction accuracy could be improved by utilization of a richer set of prognostic factors and refinement of categorical specifications.

The lamin-A/C-LAP2α-BAF1 protein complex regulates mitotic spindle assembly and positioning.

Some nuclear proteins that are crucial in interphase relocate during the G2/M-phase transition in order to perform their mitotic functions. However, how they perform these functions and the underlying mechanisms remain largely unknown. Here, we report that a fraction of the nuclear periphery proteins lamin-A/C, LAP2α and BAF1 (also known as BANF1) relocate to the spindle and the cell cortex in mitosis. Knockdown of these proteins by using RNA interference (RNAi) induces short and fluffy spindle formation, and disconnection of the spindle from the cell cortex. Disrupting the microtubule assembly leads to accumulation of these proteins in the cell cortex, whereas depolymerizing the actin microfilaments results in the formation of short spindles. We further demonstrate that these proteins are part of a stable complex that links the mitotic spindle to the cell cortex and the spindle matrix by binding to spindle-associated dynein, the actin filaments in the cell cortex and the spindle matrix. Taken together, our findings unveil a unique mechanism where the nuclear periphery proteins lamin-A/C, LAP2α and BAF1 are assembled into a protein complex during mitosis in order to regulate assembly and positioning of the mitotic spindle.

Effect of intraoperative glucose fluctuation and postoperative IL-6, TNF-α, CRP levels on the short-term prognosis of patients with intracranial supratentorial neoplasms.

OBJECTIVE: To investigate the effect of intraoperative glucose fluctuation and postoperative interlukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) levels on the short-term prognosis of patients with intracranial supratentorial neoplasms. MATERIALS AND METHODS: Eighty-six patients undergoing intracranial excision were selected in The Second Hospital of Jilin University. According to the condition of glucose fluctuation, the patients were divided into group A (glucose fluctuation <2.2 mmol/L, n=57) and group B (glucose fluctuation ≥2.2 mmol/L, n=29). Glucose was assessed by drawing 2 mL blood from internal jugular vein in two groups in the following time points, namely fasting blood glucose 1 d before operation (T0), 5 min after anesthesia induction (T1), intraoperative peak glucose (T2), intraoperative lowest glucose (T3), 5 min after closing the skull (T4), immediately after returning to intensive care unit (ICU) (T5) and 2 h after returning to ICU (T6). 1 d before operation and 1, 3 and 6 d after operation, serum IL-6 and TNF-α levels were detected with enzyme-linked immunosorbent assay (ELISA), and CRP level with immunoturbidimetry. Additionally, postoperative adverse reactions were monitored. RESULTS: There was no statistical significance between two groups regarding the operation time, anesthesia time, amount of intraoperative bleeding and blood transfusion (P>0.05). The glucose levels in both groups at T1~T6 went up conspicuously compared with that at T0 (P<0.01), and those in group B at T2, T4, T5 and T6 were significantly higher than in group A (P<0.01). Serum IL-6, TNF-α and CRP levels in both groups 1, 3 and 6 d after operation increased markedly compared with 1 d before operation (P<0.01), but the increased range in group A was notably lower than in group B (P<0.05 or P<0.01). Postoperative incidences of hypoglycemia, hyperglycemia and myocardial ischemia in group A were significantly lower than in group B (P<0.05), and respiratory support time obviously shorter than in group B (P<0.01). CONCLUSIONS: The glucose fluctuation of patients undergoing intracranial excision is related to postoperative IL-6, TNF-α and CRP levels and those with small range of glucose fluctuation have better prognosis.

On an ensemble algorithm for clustering cancer patient data.

BACKGROUND: The TNM staging system is based on three anatomic prognostic factors: Tumor, Lymph Node and Metastasis. However, cancer is no longer considered an anatomic disease. Therefore, the TNM should be expanded to accommodate new prognostic factors in order to increase the accuracy of estimating cancer patient outcome. The ensemble algorithm for clustering cancer data (EACCD) by Chen et al. reflects an effort to expand the TNM without changing its basic definitions. Though results on using EACCD have been reported, there has been no study on the analysis of the algorithm. In this report, we examine various aspects of EACCD using a large breast cancer patient dataset. We compared the output of EACCD with the corresponding survival curves, investigated the effect of different settings in EACCD, and compared EACCD with alternative clustering approaches. RESULTS: Using the basic T and N definitions, EACCD generated a dendrogram that shows a graphic relationship among the survival curves of the breast cancer patients. The dendrograms from EACCD are robust for large values of m (the number of runs in the learning step). When m is large, the dendrograms depend on the linkage functions. The statistical tests, however, employed in the learning step have minimal effect on the dendrogram for large m. In addition, if omitting the step for learning dissimilarity in EACCD, the resulting approaches can have a degraded performance. Furthermore, clustering only based on prognostic factors could generate misleading dendrograms, and direct use of partitioning techniques could lead to misleading assignments to clusters. CONCLUSIONS: When only the Partitioning Around Medoids (PAM) algorithm is involved in the step of learning dissimilarity, large values of m are required to obtain robust dendrograms, and for a large m EACCD can effectively cluster cancer patient data.