Mitofusin2 Promotes ß Cell Maturation from Mouse Embryonic Stem Cells via Sirt3/Idh2 Activation.

ß cell dysfunction is the leading cause of diabetes. Adult ß cells have matured glucose-stimulated insulin secretion (GSIS), whereas fetal and neonatal ß cells are insensitive to glucose and are functionally immature. However, how ß cells mature and acquire robust GSIS is not fully understood. Here, we explored the potential regulatory proteins of ß cell maturation process and the capacity for GSIS. Combined with the data from public databases, we found that the gene expression of Mitofusin2 (Mfn2) showed an increasing trend from mouse neonatal ß cells to mature ß cells. Moreover, its protein expression increased during mouse embryonic pancreas development and ß cell differentiation from mouse embryonic stem cells. Knocking down Mfn2 reduced Urocortin3 (Ucn3) expression, GSIS, and ATP production in induced ß cells, while overexpressing it had the opposite effect. However, neither Mfn2 knockdown nor overexpression affected the differentiation rate of insulin-positive cells. In immature and mature ß cells, Mfn2 and its correlated genes were enriched in tricarboxylic acid (TCA) cycle-related pathways. The expressions of Sirtuin 3 (Sirt3) and isocitrate dehydrogenase 2 (NADP+) and mitochondrial (Idh2) were Mfn2-regulated during ß cell differentiation. Inhibiting Idh2 or Sirt3 reduced cellular ATP content and insulin secretion levels that increased by Mfn2 overexpression. Thus, Mfn2 modulated the induced ß cell GSIS by influencing the TCA cycle through Sirt3/Idh2 activation. We demonstrated that Mfn2 promoted embryonic stem cell-derived ß cell maturation via the Sirt3/Idh2 pathway, providing new insights into ß cell development. Our data contribute to understanding diabetes pathogenesis and offer potential new targets for ß cell regeneration therapies.

Fluorouracil Supplemented With Oxaliplatin or Irinotecan for Solid Tumors: Indications From Clinical Characteristics and Health Outcomes of Patients.

Fluorouracil combined with oxaliplatin (FOLFOX) and fluorouracil combined with irinotecan (FOLFIRI) are both first-line clinical chemotherapy regimens. However, clinicians' selection of FOLFIRI or FOLFOX medication regimens and their effects on patients' health outcomes are not clear. The aim of this study was to evaluate the impacts on patient characteristics of FOLFIRI or FOLFOX medication regimen selection and the effects of each regimen on patients' health outcomes in a real-world setting. Three thousand seven hundred and twenty-five patients were retrieved and 610 of them were eventually included in this study based on the inclusion and exclusion criteria. The percentages of the TNM stage, cetuximab, bevacizumab, and tumor metastases between the FOLFIRI and FOLFOX groups were different (P < 0.001). In the multivariate Cox proportional hazards model, a significantly higher non-convalescent incidence of the FOLFOX group was found as compared with the FOLFIRI group (HR = 2.211, 95% CI = 1.257-3.888, P = 0.006). In conclusion, the TNM stage, whether combined with cetuximab or bevacizumab, and whether there was tumor metastasis presented as the key factors affecting medication selection between the FOLFIRI and FOLFOX regimens. The FOLFIRI regimen exhibited better effects on patients' long-term health outcomes than did the FOLFOX regimen. This study was registered on the World Health Organization International Clinical Trials Registry Platform (ChiCTR2000029201). Trial registration: ChiCTR2000029201.

Management of a colon cancer patient infected with corona virus disease 2019 / 浙江大学学报·医学版

OBJECTIVE@#To explore the feasibility of surgical treatment for cancer patients complicated with corona virus disease 2019 (COVID-19).@*METHODS@#The management and clinical outcome of a sigmoid cancer patient with COVID-19 were analyzed.@*RESULTS@#The inflammation indicators and fever of this patient were effectively controlled and the lung lesions remained stable after active anti-viral treatment, then the radical colorectomy was performed after the viral negative conversion for twice.@*CONCLUSIONS@#The case indicates that it may feasible to undergo radical tumor surgery for cancer patients with COVID-19 after the virus nucleic acid testing turns negative and more studies are needed to confirm this conclusion.

Management of a colon cancer patient complicated with COVID-19 / 浙江大学学报·医学版

OBJECTIVE@#To explore the feasibility of radical resection for cancer patients complicated with coronavirus disease 2019 (COVID-19).@*METHODS@#The management and clinical outcome of a sigmoid cancer patient with COVID-19 were analyzed.@*RESULTS@#The inflammation indicators and fever of this patient were effectively controlled and the lung lesions remained stable after active anti-viral treatment, then the radical colorectomy was performed after the viral negative conversion for twice.@*CONCLUSIONS@#The case indicates that radical resection can be performed in SARS-CoV-2 patients with twice-negative SARS-CoV-2 nucleic acid testing results.

Establishment of a rapid identification of adverse drug reaction program in R language implementation based on monitoring data / 浙江大学学报·医学版

OBJECTIVE@#To establish a clinically applicable model of rapid identification of adverse drug reaction program (RiADP) for risk management and decision-making of clinical drug use.@*METHODS@#Based on the theory of disproportion analysis, frequency method and Bayes method, a clinically applicable RiADP model in R language background was established, and the parameters of the model were interpreted by MedDRA coding. Based on the actual monitoring data of FDA, the model was validated by the assessing hepatotoxicity of lopinavir/ritonavir (LPV/r).@*RESULTS@#The established RiADP model included four parameters: standard value of adverse drug reaction signal information, empirical Bayesian geometric mean value, ratio of reporting ratio and number of adverse drug reaction cases. Through the application of R language parameter package "phViD", the model parameters could be output quickly. After being encoded by MedDRA, it was converted into clinical terms to form a clinical interpretation report of adverse drug reactions. In addition, the evaluation results of LPV/r hepatotoxicity by the model were matched with the results reported in latest literature, which also proved the reliability of the model results.@*CONCLUSIONS@#In this study, a rapid identification method of adverse reactions based on post marketing drug monitoring data was established in R language environment, which is capable of sending rapid warning of adverse reactions of target drugs in public health emergencies, and providing intuitive evidence for risk management and decision-making of clinical drugs.

Guideline Formulation of the Off-label Use of Drugs Based on Evidences / 中国药房

OBJECTIVE:To explore an effective method to formulate management-related strategies for off-lable use of drugs by the evidence-based medicine. METHODS:The process of guideline formulation included seven procedures,i.g. establishment ofguideliesformulation workgroup;investigation and selection of the status quo on off-label drug use;identification of the clinical problems;retrieval and evaluation and comprehensing of evidence;applification of GRADE in evidence quality grading;formation of the recommendations consensus;peer review and result publication. And eventually guidelines were formed based on the steps. This study took off-label use of rheumatoid immunoprotective subjects as a case to explore. RESULTS & CONCLUSIONS:Based on the evidence evaluation system and above 7 steps,the methods and process of guideline formulation on off-label use of rheuma-toid immunoprotective subjects that integrated administration,law,clinical medicine,pharmacy subjects were made .The process of guideline formulation fully reflects multidisciplinary characteristics of the workgroup,the advanced nature of the process,the comprehensiveness of evidence ,the rigor of evidence quality grading,and the normalization of consensus. It provides reference in methodology for establishing a comprehensive evidence-based evaluation and management system of off-label use of drugs for all clinical specialist disease. Therefore,this scientific research results may promote the standardization and legalization of the off-label use of drugs management in China.