Relationships among KRAS mutation status, expression of RAS pathway signaling molecules, and clinicopathological features and prognosis of patients with colorectal cancer

BACKGROUND The RAS/RAF/MEK/ERK and PI3 K/AKT/mTOR signaling pathways all belong to mitogen-activated protein kinase(MAPK) signaling pathways, Mutations in any one of the upstream genes(such as the RAS gene or the BRAF gene) may be transmitted to the protein through transcription or translation, resulting in abnormal activation of the signaling pathway. This study investigated the relationship between the KRAS gene mutation and the clinicopathological features and prognosis of colorectal cancer(CRC), and the effect of KRAS mutations on its associated proteins in CRC, with an aim to clarify the cause of tumor progression and drug resistance caused by mutation of the KRAS gene.AIM To investigate the KRAS gene and RAS pathway signaling molecules in CRC and to analyze their relationship with clinicopathological features and prognosis METHODS Colorectal cancer tissue specimens from 196 patients were analyzed for KRAS mutations using quantitative polymerase chain reaction and for KRAS, BRAF,MEK, and ERK protein expression levels using immunohistochemistry of tumor microarrays. To analyze differences of RAS pathway signaling molecule expression levels in different KRAS gene status, the relationships between these parameters and clinicopathological features, 4-year progression-free survival, and overall survival were analyzed by independent sample t test, Kaplan-Meier plots,and the log-rank test. Predictors of overall and disease-free survival were assessed using a Cox proportional hazards model.RESULTS Of the 196 patients, 62(32%) carried mutations in codon 12(53/62) or codon 13(9/62) in exon 2 of the KRAS gene. KRAS, BRAF, ERK, and MEK protein expression was detected in 71.4%, 78.8%, 64.3%, and 50.8% of CRC tissues,respectively. There were no significant differences between KRAS mutation status and KRAS, BRAF, MEK, or ERK protein levels. Positive expression of KRAS and ERK was associated with poor tumor differentiation, and KRAS expression was also associated with age < 56 years. MEK expression was significantly associated with distant metastasis(P < 0.05). The 4-year progression-free survival rate, but not overall survival rate, was significantly higher in patients with KRAS-negative tumors than in those with KRAS-positive tumors(P < 0.05), whereas BRAF, MEK,and ERK expression was unrelated to survival. Multivariate analysis showed that only the expression of KRAS protein was a risk factor for tumor recurrence(P <0.05). No other clinicopathological factors correlated with KRAS, BRAF, MEK, or ERK expression.CONCLUSION KRAS gene mutations do not affect downstream protein expression in CRC.KRAS protein is associated with poor tumor differentiation, older age, and a risk of tumor recurrence.

Hydrometallurgical recovery of lithium carbonate and iron phosphate from blended cathode materials of spent lithium-ion battery

The recycling of cathode materials from spent lithium-ion battery has attracted extensive attention,but few research have focused on spent blended cathode materials.In reality,the blended materials of lithium iron phosphate and ternary are widely used in electric vehicles,so it is critical to design an effective recycling technique.In this study,an efficient method for recovering Li and Fe from the blended cathode materials of spent LiFePO_(4)and LiNi_(x)Co_(y)Mn_(1-x-y)O_(2)batteries is proposed.First,87%A1 was removed by alkali leaching.Then,91.65%Li,72.08%Ni,64.6%Co and 71.66%Mn were further separated by selective leaching with H_(2)SO_(4)and H_(2)O_(2).Li,Ni,Co and Mn in solution were recovered in the form of Li_(2)CO_(3)and hydroxide respectively.Subsequently,98.38%Fe was leached from the residue by two stage process,and it is recovered as FePO_(4)·2H_(2)O with a purity of 99.5%by precipitation.Fe and P were present in FePO_(4)·2H_(2)O in amounts of 28.34%and 15.98%,respectively.Additionally,the drift and control of various components were discussed,and cost-benefit analysis was used to assess the feasibility of potential application.

New insights into the interplay between long non-coding RNAs and RNA-binding proteins in cancer

With the development of proteomics and epigenetics,a large number of RNA-binding proteins(RBPs)have been discovered in recent years,and the inter-action between long non-coding RNAs(lncRNAs)and RBPs has also received increasing attention.It is extremely important to conduct in-depth research on the lncRNA-RBP interaction network,especially in the context of its role in the occurrence and development of cancer.Increasing evidence has demonstrated that lncRNA-RBP interactions play a vital role in cancer progression;there-fore,targeting these interactions could provide new insights for cancer drug discovery.In this review,we discussed how lncRNAs can interact with RBPs to regulate their localization,modification,stability,and activity and discussed the effects of RBPs on the stability,transport,transcription,and localization of lncRNAs.Moreover,we explored the regulation and influence of these inter-actions on lncRNAs,RBPs,and downstream pathways that are related to can-cer development,such as N6-methyladenosine(m6A)modification of lncRNAs.In addition,we discussed how the lncRNA-RBP interaction network regulates cancer cell phenotypes,such as proliferation,apoptosis,metastasis,drug resis-tance,immunity,tumor environment,and metabolism.Furthermore,we sum-marized the therapeutic strategies that target the lncRNA-RBP interaction net-work.Although these treatments are still in the experimental stage and various theories and processes are still being studied,we believe that these strategiesmay provide new ideas for cancer treatment.

Effect of using electronic medication monitors on tuberculosis treatment outcomes in China: a longitudinal ecological study

Background:In China,an indigenously developed electronic medication monitor(EMM)was designed and used in 138 counties from three provinces.Previous studies showed positive results on accuracy,effectiveness,acceptability,and feasibility,but also found some ineffective implementations.In this paper,we assessed the effect of implementation of EMMs on treatment outcomes.Methods:The longitudinal ecological method was used at the county level with aggregate secondary programmatic data.All the notified TB cases in 138 counties were involved in this study from April 2017 to June 2019,and rifampicinresistant cases were excluded.We fitted a multilevel model to assess the relative change in the quarterly treatment success rate with increasing quarterly EMM coverage rate,in which a mixed effects maximum likelihood regression using random intercept model was applied,by adjusting for seasonal trends,population size,sociodemographic and clinical characteristics,and clustering within counties.