CNST is Characteristic of Leukemia Stem Cells and is Associated With Poor Prognosis in AML.

Consortin (CNST) is a protein located on the trans-Golgi network that can target transmembrane proteins to the plasma membrane. Although CNST was discovered more than 10 years ago, there are still not enough studies on its function. During our search for possible new acute myeloid leukemia (AML) markers, we found that CNST was overexpressed in almost all patients with AML. By analyzing profiling data from public databases, we found that CNST expression inversely correlated with overall survival among AML patients. There was a great variation in CNST expression among different subtypes of AML, and the expression was the highest in the t(8,21) subtype, which was probably due to the direct regulation of CNST transcription by RUNX1-RUNX1T1. In addition, we analyzed the expression of CNST in different cells of the hematopoietic system. We found that CNST was associated with the low differentiation degrees of hematopoietic cells and had the highest expression level in leukemia stem cells (LSCs). Finally, we analyzed the CNST-related gene network and found that the genes negatively correlated with CNST are involved in various immune-related pathways, which indicates that CNST is likely related to immune evasion, LSC niche retention, and assembly of stress granules. In conclusion, our study suggests that CNST has the potential to be a diagnostic and prognostic biomarker for AML.

CIGAR-seq, a CRISPR/Cas-based method for unbiased screening of novel mRNA modification regulators.

Cellular RNA is decorated with over 170 types of chemical modifications. Many modifications in mRNA, including m6 A and m5 C, have been associated with critical cellular functions under physiological and/or pathological conditions. To understand the biological functions of these modifications, it is vital to identify the regulators that modulate the modification rate. However, a high-throughput method for unbiased screening of these regulators is so far lacking. Here, we report such a method combining pooled CRISPR screen and reporters with RNA modification readout, termed CRISPR integrated gRNA and reporter sequencing (CIGAR-seq). Using CIGAR-seq, we discovered NSUN6 as a novel mRNA m5 C methyltransferase. Subsequent mRNA bisulfite sequencing in HAP1 cells without or with NSUN6 and/or NSUN2 knockout showed that NSUN6 and NSUN2 worked on non-overlapping subsets of mRNA m5 C sites and together contributed to almost all the m5 C modification in mRNA. Finally, using m1 A as an example, we demonstrated that CIGAR-seq can be easily adapted for identifying regulators of other mRNA modification.

Comparison of Efficacies of Commonly Used Hypertension Treatment Modalities: A Retrospective Study of 1900 Participants in a Hypertension Clinic.

BACKGROUND Although various antihypertensive medications are available, some hypertensive patients have uncontrolled blood pressures, especially in the clinic. The aim of the present study was to compare the efficacies of various antihypertensive therapies in our hypertension (HTN) clinic (monotherapy vs. combination therapy, fixed-dose combination (FDC) versus free equivalent combination (FEC), and diuretics versus non-diuretics. MATERIAL AND METHODS In this retrospective study, patients at the HTN clinic of the Third Xiangya Hospital with primary hypertension were enrolled from June 2016 to February 2017. Data on participants' basic characteristics, blood pressure data, and treatment modalities were collected. The proportions of participants attaining target blood pressure after treatment with antihypertensive modalities were calculated and compared. RESULTS Among 1900 participants, combination therapy had a better control efficacy than monotherapy (P<0.0005). When HTN was treated by 2 kinds of drugs, FEC was used much more frequently than FDC (P<0.0005). In grade 3 HTN, FDC had a higher control rate (P=0.002). If more than 2 kinds of drugs were used, FDC+OTHER had a slightly higher control rate in grade 2 and 3 (42.1% vs. 38.5%, P=0.724; 36.2% vs. 31.0%, P=0.526, respectively). Therapies with diuretics had better control rates than those without diuretics (43.1% vs. 36.9%, P=0.025). CONCLUSIONS In our clinic, FEC was prescribed more often than FDC. When blood pressure is significantly elevated, especially at levels 2 or 3, FDC seems to have a better control rate than FEC. Therapies with diuretics controlled HTN more efficiently.

Sex differences in antihypertensive drug use and blood pressure control.

BACKGROUND: Hypertension is the most important modifiable cardiovascular risk factor. Epidemiological studies have shown the benefits of lowering blood pressure (BP), but BP control is a major challenge. Furthermore, there are significant sex differences in antihypertensive drug use and BP control. This study examined sex differences in antihypertensive drug use and BP control, with the aim of reducing the complications of hypertension and improving quality of life. METHODS: The study was performed in our outpatient hypertension clinic, and included 1529 patients without secondary hypertension or comorbidities. The study, investigated BP control rates and patterns of antihypertensive drug use in male and female. All data were collected using structured questionnaires and patient measurements. RESULTS: The study included 713 males and 816 females in this study. Fewer females had hypertension in the younger age group (16.2% vs 11.6%; p>0.05), but this difference disappeared in middle-aged (47.8% vs 49.9 %; p<0.05) and elderly age groups (36.0% vs 38.5%; p<0.05). BP control rates differed between males and females (35.6% in male, 31.9% in female, p<0.01). There was an overall difference in BP control rates between males and females (35.6% in males, 31.9% in females, p<0.01). In this aged 18-44 years, angiotensin converting enzyme inhibitors (ACEIs) showed the best control rate in males, while calcium channel blockers (CCBs) were least effective (61.5% with ACEIs, 28.6% with CCBs; p<0.05). In this aged 45-64 years, diuretics (DUs) showed the best control rate in females, while CCBs were least effective (47.5% with DUs, 28.3% with CCBs; p<0.05). CONCLUSIONS: Sex plays an important role in BP control. In those aged 18-44 years, males using ACEIs showed best control rates. In those aged 45-64 years, females using DUs showed best control rates. Our study provides a basis with the selection of antihypertensive drugs according to sex and age.