Comparison of the PADUA and IMPROVE scores in assessing venous thromboembolism risk in 42,257 medical inpatients in China.

Venous thromboembolism (VTE) is a major contributor to hospital mortality and disability-adjusted life-year (DALY) loss. Multiple guidelines recommend using the Padua or IMPROVE scores to stratify VTE risk in hospitalized medical patients. However, the IMPROVE score is not recommended in Chinese guidelines, and there is very little evaluation of its clinical application and effectiveness in the Chinese population. The objective of this study is to compare the efficacy of the Padua and IMPROVE scoring models for assessing VTE risk in Chinese medical inpatients. We conducted a retrospective analysis of the clinical characteristics and thrombotic risk of 42,257 medical inpatients at a tertiary hospital in Guangdong, China, between 2021 and 2022. Logistic regression was used to assess thrombotic risk factors. The Receiver Operating Characteristic (ROC) curves, Area Under the Curve (AUC), sensitivity, and specificity were employed to evaluate the performance of the two models. Of the 42,257 patients included, 948 (2.24%) experienced VTE during hospitalization. According to the Padua score, 3,7513 (88.78%) of patients were considered low risk, while 4,744 (18.22%) were classified as high risk. The IMPROVE score identified 20,744 (49.09%) of patients as low risk, 20799(49.22%) as intermediate risk, and 714(1.69%) as high risk. The AUC for the Padua score was 0.735 (95% CI: 0.717-0.753), with a sensitivity of 49.4% and specificity of 89.6%. For the IMPROVE score, the AUC was 0.711 (95% CI: 0.693-0.729), with a sensitivity of 32.5% and specificity of 99.0%. The DeLong test, used to compare the AUCs, yielded a z-value of 1.886 with a P-value of 0.059, indicating no statistical difference. When assessing VTE risk in patients with stroke, cancer, nephrotic syndrome, and critical illness (ICU/CCU stay), both scoring models showed comparable predictive performance with AUCs ranging between 0.7 and 0.8. Both the Padua score and IMPROVE score have good predictive ability for VTE events during hospitalization in medical patients. Among them, the IMPROVE score has objective assessment items, simpler operation, and more detailed risk stratification, which is beneficial for clinicians to take physical and pharmacological preventive measures at different levels.ChiCTR2200056903, February 22, retrospectively registered.

Oxidative Stress and Pyroptosis in Doxorubicin-Induced Heart Failure and Atrial Fibrillation.

Patients undergoing doxorubicin (Dox) chemotherapy often develop new-onset atrial fibrillation and heart failure. Recent studies indicate that the TLR4/MyD88/NLRP3 pyroptosis signaling pathway plays a key role in the occurrence and development of cancer, heart failure, and atherosclerosis. However, few studies investigated the role of oxidative stress and pyroptosis in doxorubicin-induced heart failure and new-onset atrial fibrillation. In this study, we recruited 84 healthy subjects, 112 patients undergoing Dox chemotherapy showing heart failure (HF), and 62 patients undergoing Dox treatment who manifested atrial fibrillation (AF). The mRNA and protein levels of TLR4 expression, several downstream pyroptosis-associated proteins (cleaved caspase-1, NLRP3, GSDMD-N, and HMGB-1), serum inflammatory factors, and oxidative stress were detected at the beginning of chemotherapy and after 3 months of Dox chemotherapy. Oxidative stress and downstream pyroptosis-associated proteins tended to increase in the Dox-baseline group to the Dox-HF group. However, virtually no change in the expression of either oxidative stress or pyroptosis-associated proteins was detected in patients after three months of Dox chemotherapy compared with those at baseline. This study suggests that the prolonged oxidative stress and high levels of pyroptosis-associated proteins contribute to cardiac systolic dysfunction, suggesting TLR4 as a novel biomarker and a potential treatment target for doxorubicin-induced heart failure.

Development and validation of a noninvasive prediction model for identifying eosinophilic asthma.

BACKGROUND: Identification of eosinophilic asthma (EA) using sputum analysis is important for disease monitoring and individualized treatment. But it is laborious and technically demanding. We aimed to develop and validate an effective model to predict EA with multidimensional assessment (MDA). METHODS: The asthma patients who underwent a successful sputum induction cytological analysis were consecutively recruited from March 2014 to January 2021. The variables assessed by MDA were screened by least absolute shrinkage and selection operator (LASSO) and logistic regression to develop a nomogram and an online web calculator. Validation was performed internally by a bootstrap sampling method and externally in the validation cohort. Diagnostic accuracy of the model in different asthma subgroups were also investigated. RESULTS: In total of 304 patients in the training cohort and 95 patients in the validation cohort were enrolled. Five variables were identified in the EA prediction model: gender, nasal polyp, blood eosinophils, blood basophils and FeNO. The C-index of the model was 0.86 (95% CI: 0.81-0.90) in the training cohort and 0.84 (95% CI: 0.72-0.89) in the validation cohort. The calibration curve showed good agreement between the prediction and actual observation. The decision curve analysis (DCA) also demonstrated that the EA prediction model was clinically beneficial. An online publicly available web calculator was constructed (https://asthmaresearcherlimin.shinyapps.io/DynNomapp/). CONCLUSION: We developed and validated a multivariable model based on MDA to help the diagnosis of EA, which has good diagnostic performance and clinical practicability. This practical tool may be a useful alternative for predicting EA in the clinic.

Childhood trauma and the plasma levels of IL-6, TNF-α are risk factors for major depressive disorder and schizophrenia in adolescents: A cross-sectional and case-control study.

BACKGROUND: It has been reported that childhood trauma and inflammation are associated with major depressive disorder (MDD) and schizophrenia (SZ), but previous researches were almost aimed at adults. The aim of the present research is to observe the alteration of peripheral interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in adolescents (12-20 years) with MDD and SZ, to investigate the impact of childhood abuse in early-onset MDD and SZ, and to furtherly explore the correlation between childhood maltreatment and plasma IL-6, TNF-α levels. SUBJECTS AND METHODS: Enzyme-linked immunosorbent assay (ELISA) is applied to obtain the plasma concentrations of IL-6 and TNF-α in 55 patients with MDD, 51 patients with SZ and 47 healthy minors. The short form of the Childhood Trauma Questionnaire (CTQ-SF) is used to assess the severity of early trauma. RESULTS: Plasma IL-6 and TNF-α levels are significantly elevated in patients with early-onset MDD and SZ compared with healthy subjects (p <0.01), whose results display that the correlation between IL-6 and TNF-α is significantly positive (γ=0.787, p <0.01) in all participants. Compared with the healthy adolescents, patients with MDD and SZ show more serious childhood trauma, and the plasma IL-6, TNF-α concentrations are closely related to childhood maltreatment. CONCLUSIONS: Early trauma and peripheral inflammatory response play an important role in the pathophysiology of early-onset MDD or SZ. The current findings provide effective targets for the prevention, diagnosis, and treatment of major depressive disorder and schizophrenia in adolescents.

Treatment mode and prognosis of esophageal perforation after radiotherapy in patients with esophageal carcinoma.

Objective: Retrospectively analyzed the esophageal carcinoma (EC) patients with esophageal perforation (EP) after radiotherapy to discuss the treatment and prognosis. Methods: Data of patients with EC who had EP after radiotherapy in Hebei Cancer Hospital were collected from 2001 to 2020 and retrospectively analyzed. All analyses were performed using SPSS Statistics for Windows, version 18. 0 (SPSS Inc., Chicago, Ill., USA). P values less than 0.05 were considered statistically significant. Results: A total of 94 patients with EC were enrolled, among which 72 were males and 22 were females, with a median age of 62 (38-82) years. The tumor was located in the upper thoracic in 45 patients, middle thoracic in 45 patients, and lower thoracic in 4 patients. There were 30 cases of tracheoesophageal fistula (TEF) and 64 cases of esophagomediastinal fistula (EMF). All patients died within 11 months (median: two months) after EP. After EP, 48 patients were treated by tube feeding (include nasal feeding and gastrostomy), 26 patients by esophageal stenting, and 20 patients by fluid infusion therapy, and their one, three, and six months survival rates after EP were 81.3%, 31.3%, and 12.5% (P = 0.000). In the TEF group, the one, three, and six month survival rates after EP of tube feeding, esophageal stenting and fluid infusion groups were 88.2%, 17.6%, 11.8%; 45.5%, 27.3%, 0%; and 50.0%, 50.0%, 0% (P = 0.345). In the EMF group, the one, three, and six months survival rates after EP of this three groups were 77.4%, 38.7%, 12.9%; 26.7%, 20.0%, 6.7%; and 22.2%, 11.1%, 0% (P=0.002), respectively. Conclusion: Most patients with EP after radiotherapy died within six months, with low survival and poor prognosis. Tube feeding therapy can achieve relatively good survival, especially for patients with EMF. The survival of patients treated by tube feeding therapy is significantly better than the survival of those treated by other methods.

Clinical outcomes of salvage radiotherapy in patients with supraclavicular lymph node metastases after esophagectomy.

Purpose: To evaluate the clinical outcomes of salvage radiotherapy in patients with supraclavicular lymph node (SCLN) metastases after esophagectomy. Methods: After initial esophagectomy (R0 resection), clinical outcomes in patients with esophageal squamous cell carcinoma with SCLN metastases during follow-up were retrospectively analyzed. Results: A total of 114 patients were split into two groups: the salvage radiotherapy (SR) (n=89) and the control (NSR) (without salvage radiotherapy, n=25). The overall survival rates of 1 year, 3 years and 5 years were 81.6%, 31.4% and 8.6%, accordingly. The 1-year and 3-year survival after SCLN metastases (SASM) rates were 40.2% and 14.5%, respectively; the median SASM time was 10 months. In the SR group, the SASM rates of 1-year and 3-year were 48.1% and 18.9%, compared to 12.0% and 0% in the NSR group (p<0.001). Patients in the SR group who received combined radiochemotherapy experienced 1-year and 3-year SASM rates of 62.6% and 33.4%, compared to 41.9% and 16.5% with single radiotherapy (p<0.001). The salvage radiation dose revealed that the 1-year and 3-year SASM rates turned out to be 56.5% and 23.4% in group of ≥60 Gy, and 29.2% and 7.5% in group of <60 Gy (p<0.001). According to multivariate analysis, combined visceral metastases (CVM), combined mediastinal failure (CMF), salvage radiotherapy, salvage radiation dose and salvage treatment method possibly were identified as important prognostic variables. After propensity score matching (PSM), the above results were similar to those before PSM, except for that only salvage radiotherapy is possibly independent prognostic variables for survival after SCLN metastases in multivariate analysis. Conclusion: It is possible that salvage radiotherapy can increase the survival rate of patients who receive SCLN metastases following esophagectomy.

GAPDH siRNA Regulates SH-SY5Y Cell Apoptosis Induced by Exogenous α-Synuclein Protein.

The transport mechanism of intestinal α-synuclein to the central nervous system has become a new hot topic in Parkinson's disease (PD) research. It is worth noting that the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has been reported to be involved in the pathogenesis of PD. After silencing GAPDH expression by GAPDH siRNA, the normal human intestinal epithelial crypt-like (HIEC) and human SH-SY5Y neuroblastoma cell lines were co-cultured with Escherichia coli cells which were transfected with an α-synuclein overexpression plasmid. The levels of autophagy-related proteins (BECN1, ATG5, LC3A/B and p62) were determined by Western blot analysis. Changes in pro-apoptosis protein levels and flow cytometry analysis were used to assess cell apoptosis and relative intracellular ATP concentration was measured. Oxidative stress was assessed by measuring the levels of reactive oxygen species (ROS) using 2',7'-dichlorofluorescein diacetate (DCFH-DA), thiobarbituric acid-reactive substances (TBARS), and antioxidant capacity was assessed by measuring the glutathione (GSH) levels and superoxide dismutase (SOD) activity. The silencing of the expression of GAPDH pre-knockdown was found to reduce the intracellular levels of ROS and lipid peroxidation, enhance autophagy activity, thereby reducing the cell injury, apoptosis and necrosis induced by exogenous α-synuclein protein in SH-SY5Y cells. This study identifies a new therapeutic target of exogenous α-synuclein protein induced SH-SY5Y cell injury and improves our understanding of the pathophysiological role of GAPDH in vitro.

Clinical characteristics and prognosis of pulmonary large cell carcinoma: A population-based retrospective study using SEER data.

BACKGROUND: Pulmonary large cell carcinoma (LCC) is an infrequent neoplasm with a poor prognosis. This study explored the clinical characteristics and survival prognostic factors of LCC patients. METHODS: Patient data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Chi-square tests or rank-sum tests were used to compare differences in clinical characteristics. Log-rank tests, univariate, and multivariate analyses were performed to investigate the independent factors of survival. Analyses of stage I-IV patients were performed to further explore the optimal treatment. RESULTS: In total, 3197 LCC patients were included in this analysis. Compared with other non-small cell lung cancers (NSCLCs), there was a worse overall survival (OS) from LCC. LCC was more common in males, over age 60 and in the upper lobe. A total of 73.6% of patients were stage III/IV. The median OS of stage I-IV patients was 42 months, 22 months, 11 months, and three months, respectively. The elderly, males, later stage, and main bronchus location, or overlapping lesions were risk factors for survival prognosis. In stage I-III patients, treatment including surgery could significantly reduce the risk of death by 60% at least compared with no therapy. Surgery was still beneficial for stage IV patients, and the hazard ratio (HR) compared with no therapy was 0.462 (P = 0.001). CONCLUSIONS: Our study concluded that LCC has unique clinical features, and that age, sex, primary site, stage, and treatment are significantly related to OS. Surgery based comprehensive treatments are effective for LCC. KEY POINTS: Significant findings of the study In stage IV patients, chemotherapy or radiotherapy combined with surgery could further improve survival. When surgical resection involved more than one lobe, it may be beneficial for survival prognosis. What this study adds LCC patients were principally male and over age 60, with later stages and poor survival prognosis. Age, sex, stage, primary site and therapy are closely related to survival.

Oxidative Stress in Radiation-Induced Cardiotoxicity.

There is a distinct increase in the risk of heart disease in people exposed to ionizing radiation (IR). Radiation-induced heart disease (RIHD) is one of the adverse side effects when people are exposed to ionizing radiation. IR may come from various forms, such as diagnostic imaging, radiotherapy for cancer treatment, nuclear disasters, and accidents. However, RIHD was mainly observed after radiotherapy for chest malignant tumors, especially left breast cancer. Radiation therapy (RT) has become one of the main ways to treat all kinds of cancer, which is used to reduce the recurrence of cancer and improve the survival rate of patients. The potential cause of radiation-induced cardiotoxicity is unclear, but it may be relevant to oxidative stress. Oxidative stress, an accumulation of reactive oxygen species (ROS), disrupts intracellular homeostasis through chemical modification and damages proteins, lipids, and DNA; therefore, it results in a series of related pathophysiological changes. The purpose of this review was to summarise the studies of oxidative stress in radiotherapy-induced cardiotoxicity and provide prevention and treatment methods to reduce cardiac damage.

The role of toll-like receptors in myocardial toxicity induced by doxorubicin.

Doxorubicin is an effective antitumor drug commonly used in the treatment of a wide variety of cancers. However, doxorubicin may cause cardiac toxicity, which can cause congestive heart failure in severe cases, and this seriously limits its clinical application. It is believed that doxorubicin promotes the formation of reactive oxygen species, inducing oxidative stress, and at the same time, reduces the content of antioxidant substances in cardiac tissues, causing adverse effects. Toll-like receptors (TLRs) are biomolecules expressed on the surfaces of macrophages, dendritic cells, and epithelial cells that can recognize various types of pathogen-related or damage-related molecular patterns. In recent years, a large number of studies have confirmed that TLRs play important roles in the cardiac toxicity induced by doxorubicin. This review aimed to explore the role of TLRs in the cardiac toxicity induced by doxorubicin and provide possible solutions.

Predictors of Occult Lymph Node Metastasis and Prognosis in Patients with cN0 T1-T2 Supraglottic Laryngeal Carcinoma: A Retrospective Study.

BACKGROUND: This work aimed to explore the predictors of lymph node metastasis (LNM) and analyze the prognosis of patients with clinically node-negative (cN0) T1-T2 supraglottic laryngeal carcinoma (SGLC). METHODS: Data for 130 patients with cN0 T1-T2 SGLC who initially underwent surgery were retrospectively reviewed. Occult LNM incidence, relevant factors, and prognosis were analyzed. RESULTS: Of the 130 patients with cN0 T1-T2 SGLC, 21 (16.2%) had occult LNM. Based on univariate and multivariable regression analyses, male sex and poor tumor differentiation predicted the incidence of occult LNM. The incidence of occult LNM was 20.9% in males and 5.1% in females (p = 0.035). Patients with poorly differentiated tumors had a higher incidence of occult LNM (42.9%) than patients with well-differentiated (10.3%) and moderately differentiated tumors (14.3%; p < 0.05). Thirteen patients (10%) had cervical recurrence, and all had T2 tumors (p = 0.02). The 5-year disease-specific survival rates were 70 and 90% for patients with and without LNM, respectively (p = 0.000). CONCLUSIONS: Sex and tumor differentiation are potential predictors of occult nodal disease. Female patients with cN0 T1-T2 SGLC are less likely than male patients to have neck metastasis. Poorly differentiated tumors are associated with the frequency of neck metastasis, and selective neck dissection is strongly recommended for these tumors.

Asymmetrical methyltransferase PRMT3 regulates human mesenchymal stem cell osteogenesis via miR-3648.

Histone arginine methylation, which is catalyzed by protein arginine methyltransferases (PRMTs), plays a key regulatory role in various biological processes. Several PRMTs are involved in skeletal development; however, their role in the osteogenic differentiation of mesenchymal stem cells (MSCs) is not completely clear. In this study, we aimed to elucidate the function of PRMT3, a type-I PRMT that catalyzes the formation of ω-mono- or asymmetric dimethyl arginine, in MSCs osteogenesis. We found that PRMT3 promoted MSCs osteogenic commitment and bone remodeling. PRMT3 activated the expression of miR-3648 by enhancing histone H4 arginine 3 asymmetric dimethylation (H4R3me2a) levels at promoter region of the gene. Overexpression of miR-3648 rescued impaired osteogenesis in PRMT3-deficient cells. Moreover, administration of Prmt3 shRNA or a chemical inhibitor of PRMT3 (SGC707) caused an osteopenia phenotype in mice. These results indicate that PRMT3 is a potential therapeutic target for the treatment of bone regeneration and osteopenia disorders.

Digital Analysis of Immunostaining of ZW10 Interacting Protein in Human Lung Tissues.

The purpose of this study is to introduce a methodology of the immunostaining of human lung tissues, followed by whole-slide digital scanning and image analysis. Digital scanning is a fast way to scan a stack of slides and produce digital images with high quality. It can produce concordant results with conventional light microscopy (CLM) by pathologists. Furthermore, the availability of digital images makes it possible that the same slide can be concurrently observed by multiple people. Moreover, digital images of slides can be stored in a database, which means the long-term deterioration of glass slides is avoided. The limitations of this technique are as follows. First, it needs high-quality prepared tissue and the original immunohistochemistry (IHC) slides without any damage or excess sealant residue. Second, tumor or nontumor areas should be specified by experienced pathologists before the analysis using software, in order to avoid any confusion about the tumor or nontumor areas during scoring. Third, the operator needs to control the color reproduction throughout the digitization process in whole-slide imaging.

Oxidative stress injury in doxorubicin-induced cardiotoxicity.

Doxorubicin (DOX) is widely used as a broad-spectrum anti-tumor anthracycline to treat various cancers. The serious adverse effects of DOX on cardiotoxicity limit its clinical application. There are several different mechanisms involved in DOX-induced cardiotoxicity. Oxidative stress (OS) is caused by an imbalance between reactive oxygen species (ROS) and endogenous antioxidants in response to injury, which can lead to myocardial toxicity. The aim of this review was to investigate the mechanisms underlying the effects of oxidative stress injury on myocardial toxicity, from three different aspects: the increase in downstream oxidative stress products, the reduction in upstream antioxidative stress products, and subcellular organelles. Finally, there are some anti-oxidative drugs that show efficacy in limiting DOX-induced cardiotoxicity. It is necessary to fully understand the toxicity of DOX to the myocardium and achieve symptomatic treatment.

TLR2 and TLR3 expression as a biomarker for the risk of doxorubicin-induced heart failure.

Doxorubicin (Dox) is limited in its use because of its adverse effect of inducing irreversible heart dysfunction. Innate immune factors, including toll-like receptors (TLRs), play important roles in most cardiac diseases and doxorubicin-induced cardiotoxicity. In this study, subjects were divided into the following groups: healthy controls (n = 62), HF group (n = 60), Dox group (n = 82), and Dox-HF group (n = 32). Expressions of TLR mRNAs in peripheral blood mononuclear cells were detected by RT-PCR. Western blotting was used to quantify protein expressions of Peripheral blood mononuclear cells (PBMCs) TLRs and their downstream signal proteins. The release of inflammatory factors was detected by ELISA. Results indicated that TLR2 was increased and TLR3 was decreased between the control group and Dox group, and between the Dox group and Dox-HF group. Serum inflammatory factors were comparable between the HF group, the Dox group, and the Dox-HF group. This study suggested that TLR2 and TLR3 are up- and down-regulated, respectively, in doxorubicin-treated patients who develop heart dysfunctions. This may suggest a predictive role for TLR2-TLR3 imbalance in doxorubicin-induced heart failure.

Familial Nonmedullary Thyroid Carcinoma: A Retrospective Analysis of 117 Families.

BACKGROUND: The first and most important step in characterizing familial nonmedullary thyroid carcinoma (NMTC) is to distinguish the true familial patients, which is the prerequisite for all accurate analyses. This study aimed to investigate whether patients from families with ≥3 first-degree relatives affected with NMTC have different characteristics than patients from families with only two affected members, and to compare these patients with those with sporadic disease. METHODS:: We analyzed the clinicopathological features and prognosis of 209 familial and 1120 sporadic cases of NMTC. Familial patients were further divided into two subgroups: families with two affected members and families with ≥3 affected members. RESULTS:: The familial group had a significantly higher risk of bilateral growth, multifocality, extrathyroidal extension, and lateral lymph node metastasis than the sporadic group (P < 0.05). These main features were also different between the group with ≥3 affected members and the sporadic group. The only difference between the two affected members' group and the sporadic group was incidence of multifocality (P < 0.05). The probability of disease recurrence in patients from families with ≥3 affected members was significantly higher than that in sporadic cases (14.46% vs. 5.27%; P = 0.001), while the probability in patients from families with two affected members was similar to that in sporadic patients (6.35% vs. 5.27%; P = 0.610). The Kaplan-Meier survival analysis showed a statistically significant difference in disease-free survival between the two subgroups (85.54% vs. 93.65%; P = 0.045). CONCLUSIONS:: Patients from families with ≥3 members affected by NMTC have more aggressive features and a worse prognosis than those from families with only two affected members. Patients from families with ≥3 affected first-degree relatives may be considered to have true familial NMTC.

C1206, a novel curcumin derivative, potently inhibits Hsp90 and human chronic myeloid leukemia cells in vitro.

4-(4-Pyridinyl methylene) curcumin (C1206) is a new derivative of curcumin that is more active than curcumin in inhibition of heat shock protein 90 (Hsp90) and antitumor action. In this study we investigated the relationship between C1206-induced inhibition of Hsp90 and its anti-leukemic effects. The fluorescence quenching experiments showed that C1206 seemed to bind the middle dimerization domain of Hsp90. The interaction between C1206 and Hsp90 was driven mainly by electrostatic interaction. In in vitro enzyme activity assay, C1206 dose-dependently inhibited Hsp90 ATPase activity with an IC50 value of 4.17 µmol/L. In both imatinib-sensitive K562 chronic myeloid leukemia cells and imatinib-resistant K562/G01 chronic myeloid leukemia cells, C1206 (0.4-3.2 µmol/L) dose-dependently caused the degradation of Hsp90 client proteins and downstream proteins (AKT, MEK, ERK, C-RAF, P-AKT, P-MEK and P-ERK). Furthermore, C1206 (0.4-3.2 µmol/L) dose-dependently induced apoptosis of K562 and K562/G01 cells through triggering mitochondrial pathway. Consistent with this result, C1206 inhibited the proliferation of K562 and K562/G01 cells with IC50 values of 1.10 and 0.60 µmol/L, respectively. These results suggest that C1206 is a novel Hsp90 inhibitor and a promising therapeutic agent for chronic myeloid leukemia.

TMED2 promotes epithelial ovarian cancer growth.

TMED2 is involved in morphogenesis of the mouse embryo and placenta. We found that expression of TMED2 was higher in epithelial ovarian cancer tissues than normal ovarian tissues. Silencing TMED2 decreased cell proliferation, migration, and invasion. Ectopic expression of TMED2 increased cell proliferation, migration and invasion. Silencing TMED2 inhibited ovarian cancer growth in mice. Silencing TMED2 inhibited IGF2/IGF1R/PI3K/Akt pathway. In agreement, ectopically expressed TMED2 activated IGF2/IGF1R/PI3K/Akt pathway. Mechanistic study revealed that TMED2 directly binds to AKT2, thereby facilitating its phosphorylation. We also found that TMED2 increased IGF1R expression by competing for miR-30a. Thus, TMED2 is oncogenic and a potential target for epithelial ovarian cancer therapy.

TNF Receptor 1/2 Predict Heart Failure Risk in Type 2 Diabetes Mellitus Patients.

Inflammation plays an important role in heart failure and diabetes mellitus. Traditional serum markers have limited predictive value in heart failure and diabetes. TNFR1 and TNFR2 (TNFR1/2) have been proven to be strongly associated with heart failure and diabetes complications. This study aimed to assess the association of sTNFR1 and sTNFR2 levels and incidental HF risk in diabetes patients.We detected the mRNA, protein, and serum expression of TNFR1/2, their downstream signaling pathway protein NF-kB, and JNK expression and some traditional serum inflammatory markers in a heart failure group without diabetes mellitus or abnormal glucose tolerance (n = 84), a diabetes mellitus group without heart failure (n = 86), and a heart failure with diabetes mellitus group (n = 86).TNFR1/2 were significantly higher in patients with heart failure and diabetes mellitus based on mRNA expression to protein expression and serum expression. However, there were no differences in mRNA, protein, and serum levels of TNFR1/2 between the HF group and DM group. Furthermore, there were no differences between the groups in some traditional serum inflammatory markers.This study demonstrated higher expressions of TNFR, NF-kB, and JNK in patients with heart failure and diabetes mellitus. Compared with traditional serum markers, TNFR1 and TNFR2 are associated with heart failure risk in type 2 diabetes mellitus patients.

Cysteine and glycine-rich protein 2 (CSRP2) transcript levels correlate with leukemia relapse and leukemia-free survival in adults with B-cell acute lymphoblastic leukemia and normal cytogenetics.

Relapse is the major cause of treatment-failure in adults with B-cell acute lymphoblastic leukemia (ALL) achieving complete remission after induction chemotherapy. Greater precision identifying persons likely to relapse is important. We did bio-informatics analyses of transcriptomic data to identify mRNA transcripts aberrantly-expressed in B-cell ALL. We selected 9 candidate genes for validation 7 of which proved significantly-associated with B-cell ALL. We next focused on function and clinical correlations of the cysteine and glycine-rich protein 2 (CSRP2). Quantitative real-time polymerase chain reaction (RT-qPCR) was used to examine gene transcript levels in bone marrow samples from 236 adults with B-cell ALL compared with samples from normals. CSRP2 was over-expressed in 228 out of 236 adults (97%) with newly-diagnosed B-cell ALL. A prognostic value was assessed in 168 subjects. In subjects with normal cytogenetics those with high CSRP2 transcript levels had a higher 5-year cumulative incidence of relapse (CIR) and worse relapse-free survival (RFS) compared with subjects with low transcript levels (56% [95% confidence interval, 53, 59%] vs. 19% [18, 20%]; P = 0.011 and 41% [17, 65%] vs. 80% [66-95%]; P = 0.007). In multivariate analyses a high CSRP2 transcript level was independently-associated with CIR (HR = 5.32 [1.64-17.28]; P = 0.005) and RFS (HR = 5.56 [1.87, 16.53]; P = 0.002). Functional analyses indicated CSRP2 promoted cell proliferation, cell-cycle progression, in vitro colony formation and cell migration ability. Abnormal CSRP2 expression was associated with resistance to chemotherapy; sensitivity was restored by down-regulating CSRP2 expression.