Cullin-9/p53 mediates HNRNPC degradation to inhibit erastin-induced ferroptosis and is blocked by MDM2 inhibition in colorectal cancer.

Colorectal cancer (CRC) is the leading cause of cancer associated death worldwide. Ferroptosis is a newly defined form of regulated cell death characterized by the accumulation of lipid hydroperoxides and exerts an increased attention for cancer treatment. However, little is known about ferroptosis in CRC. In this study, through whole genome sequencing and external differential differentiated expression analysis, we identify CUL9 as a novel important modulator for ferroptosis in CRC. Here we demonstrated that CUL9 can binds p53 to ubiquitylate heterogeneous nuclear ribonucleoprotein C for degradation. Overexpression of CUL9 increases resistance to erastin-induced ferroptosis. Then, we discovered this resistance was mediated by CUL9-HNRNPC-MATE1 negative loop, which can provide us with a novel target to overcome drug resistance to ferroptosis activators. Finally, we found that targeting MDM2 was developed as an effective strategy to destroy precious drug-resistant CRC cells.

Preliminary study of risk management mode for investigator-initiated clinical trials / 中华医学科研管理杂志

Objective To explore the risk management model of investigator-initiated clinical trials (IITs) from the prospective of clinical research management personnel,to provide further reference for its construction and implementation in China.Methods The risks in IITs and its current situation of risk management were analyzed.Risk management standards including ISO 31000 and related guidelines were adopted to explore the risk management mode for China-based IIT.Results This article proposed the new risk management mode for IITs and also introduced the specified frame and procedures of related risk management.Conclusions The risk management model proposed in this article provided reference for clinical research management.

Problem exploration and measures on the investigator initiated trial from the perspective of scientific research supervision / 中华医学科研管理杂志

Objective By analyzing the problems existed in the Investigator Initiated Trial (IIT),this article put forward the corresponding countermeasures and therefore provides reference for the standardization of clinical research project management.Methods Four types of problems identified in the supervision of hospital IIT projects are analyzed according to literature review,data analysis of clinical research project,comparative study and summary.Identified problems are existed in the following aspects:scientific research supervision function,research method guidelines,technical specification of the diagnosis and treatment,scientific research design and project approval review,research funds,medical ethics committee,construction of Biobank and Regulation Conflicts.Results This article put forward 6 countermeasures for improvement:establishing and perfect IIT project scientific research supervision entity,bring in the IIT project steering group to strengthen the scientific review;Strengthen risk management to ensure medical safety,carry out IIT training,establish IIT management database information system,build a comprehensive integrated development multi-point application model of hospital BioBank.Conclusions The establishment of the hospital's IIT scientific research supervision system,management mode and technical standard system is of great importance to standardize clinical research,ensure research quality and guide the clinical research work of the hospital effectively.

Recent advances in the treatment of colorectal liver metastases / 中华消化外科杂志

Liver metastasis is the leading cause of death from colorectal cancer (CRC).Multidisciplinary team model has become standard strategy for the diagnosis and treatment of colorectal liver metastases (CRLM),making individualized treatment through precise staging and molecular typing.Preoperative hepatic and regional arterial infusion chemotherapy and portal vein chemotherapy during surgery can reduce the incidence of liver metastases for stage Ⅲ CRC.Surgical resection of CRLM has been accepted by all scholars,and can be performed by minimally invasive surgery.The criteria for hepatic resection of CRLM have been extended including complete tumor resection,negative resection margin and adequate remnant liver volume.Simultaneous resections of primary tumor and liver metastases are safe and feasible.However,neoadjuvant chemotherapy is still controversial.For unresectable liver metastases,conversion therapy should be implemented to make the liver metastases become resectable.For unconvertible and unresectable CRLM,aggressive and comprehensive treatment is required to control the disease progression.

Analysis of long-term outcomes and risk factors in patients undergoing simultaneous resection of synchronous colorectal liver metastasis / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To analyze long-term outcomes and related risk factors in patients undergoing simultaneous resection of synchronous colorectal liver metastasis.</p><p><b>METHODS</b>Clinicopathological, short- and long-term outcome data of 154 consecutive synchronous colorectal liver metastasis patients who underwent simultaneous resection between July 2003 and July 2013 were collected and analyzed with Cox multivariate methods retrospectively.</p><p><b>RESULTS</b>No perioperative death was found. A total of 46 patients (29.9%) had complications, which were all successfully treated medically or by percutaneous drainage. The 5-year overall survival rate was 46%, and the 5-year disease-free survival rate was 35%. Four factors were found to be independent predictors of poor overall survival by multivariate analysis: positive lymph node status (P=0.000), number of metastasis focus (≥4) (P=0.017), bilobar liver metastasis distribution (P=0.004) and non-R0 resection of liver metastasis (P=0.001). Three factors were found to be independent predictors of poor disease-free survival by multivariate analysis: positive lymph node status (P=0.031), bilobar liver metastasis distribution (P=0.001) and extrahepatic metastases (P=0.020).</p><p><b>CONCLUSIONS</b>Simultaneous resection of synchronous colorectal liver metastasis is safe and its short- and long-term outcomes are quite good. Positive lymph node status, number of metastasis focus (≥4), bilobar liver metastasis distribution, non-R0 resection of liver metastasis and extrahepatic metastasis are risk factors of poor long-term prognosis.</p>

Poincare mapping method for T-wave alternans using a nonlinear dynamic system / 中国组织工程研究

BACKGROUND:The microvolt T-wave alternans (MTWA) is an important index for ventricular arrhythmias prediction and is a promising tool to evaluate non-invasively malignant ventricular arrhythmia and risk of sudden death.OBJECTIVE:To introduce a algorithm for detecting TWA using Poincare mapping method (PM),which is a technique for dynamics systems to display periodic behavior.METHODS:Samples series of beat to beat cycles were selected to prepare Poincare mapping to describe TWA distdbution.D_(twa),which denoted the sum distances between the origin to even and odd series,was used to present the presence and absence of TWA.RESULTS AND CONCLUSION:This algorithm was applied in MIT/BIH Arrhythmia database and European ECG ST-T database,and D_(twa) used for correlation analysis with V_(twa),which denoted TWA amplitude of Spectrum Method.The cross-correlation coefficient was γ= 0.984.The algorithm can identify the absence and presence of TWA accurately and provide idea for further study of TWA-PM.

Correlation between Distribution of Retail Pharmacies and Population Distribution in Wuhan City / 中国药房

OBJECTIVE: To study the correlation between distribution of pharmacies and that of population in Wuhan. METHODS: Pearson correlation test and Spearman's rank correlation test were applied for the statistical analysis of the correlation between distribution of pharmacies and that of population. RESULTS: The distribution of retail pharmacies was in a significant positive correlation with that of population; However, in some areas of Wuhan, the distribution of retail pharmacies was characterized by relative insufficient or oversaturation. CONCLUSIONS: Many factors led to the lack of rationality in the distribution of retail pharmacies in some area in Wuhan. Drug control department should standardize examination and approval standards and the retail pharmacies should have a reasonable overall planning.