Essential hypertension (EH) is a principal contributing factor in worldwide cardiovascular disease mortality. Although interventions that minimize environmental risk factors for EH are associated with reduced cardiovascular disease, such approaches are limited for individuals with high genetic EH risk. In this study, we investigated possible associations between ACE2 polymorphisms and hypertension-related target organ damages in south Xinjiang, China. Four hundred and two hypertensive patients were enrolled as study participants in an EH group, and 233 normotensive individuals were enrolled as control subjects. Participants were recruited from the south Xinjiang region. Fourteen ACE2 polymorphisms were genotyped by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Risk genotypes of rs2074192 (TT+CT, OR = 1.72, 95% CI: 1.17–2.53), rs2106809 (TT, OR = 1.71, 95% CI: 1.13–2.58), rs4240157 (CC+CT, OR = 1.99, 95% CI: 1.17–3.41), rs4646155 (TT+CT, OR = 1.94, 95% CI: 1.06–3.54), rs4646188 (TT+CT, OR = 3.25, 95% CI: 1.95–5.41), rs4830542 (CC+CT, OR = 1.88, 95% CI: 1.10–3.23), and rs879922 (CC+CG, OR = 4.86, 95% CI: 2.74–8.64) were associated with EH. Hypertensive patients carrying the control genotype of rs2074192 (CC, OR = 2.37, 95% CI: 1.28–4.39) were associated with CAS ≥50%, while those carrying a high-EH-risk genotype of rs4240157 (OR = 2.62, 95% CI: 1.24–5.54), rs4646155 (OR = 2.44, 95% CI: 1.16–5.10), or rs4830542 (CC+CT, OR = 2.20, 95% CI: 1.03–4.69) were associated with atrial fibrillation (AF), larger left atrial diameter, and higher levels of renin–angiotensin–aldosterone system (RAAS) activation (renin and angiotensin I/II). In conclusion, the ACE2 variant rs2074192 was associated with EH and EH with CAS ≥50%, while 3 ACE2 variants (rs4240157, rs4646155, and rs4830542) were associated with EH- and hypertension-related AF and left atrial remodeling in south Xinjiang, China.

Type 2 diabetes mellitus (T2D), rapidly increasing to epidemic proportions, globally escalates cardiovascular disease risk. Although intensive interventions and comprehensive management of environmental risks factors for T2D are associated with reduced cardiovascular disease, such approaches are limited for individuals with high genetic T2D risk. In this study we investigated possible associations of ACE2 polymorphisms and cardiovascular risks in Uygur patients with T2D. 275 Uygur T2D patients and 272 non-diabetic Uygur individuals were enrolled as study participants. 14 ACE2 polymorphisms were genotyped by Matrix-assisted laser desorption ionization time-of-flight mass spectrometry. ACE2 SNP rs1978124, rs2048683, rs2074192, rs233575, rs4240157, rs4646156, rs4646188 and rs879922 were associated with T2D (all P < 0.05). The 8 diabetic risk related ACE2 SNPs were further associated with diabetic related cardiovascular complications or events but exhibited heterogeneity as fellows: firstly, almost all diabetic risk related ACE2 SNPs (all P < 0.05) were associated with increased SBP except rs1978124 and rs2074192, while rs2074192, rs4646188 and rs879922 were associated elevated DBP (all P < 0.05). Secondly, SNP rs4646188 was not correlated with any type of dyslipidemia (TRIG, HDL-C, LDL-C or CHOL), and the other 7 diabetic risk related loci were at least correlated with one type of dyslipidemia (all P < 0.05). In particular, rs879922 were simultaneously correlated with four type of dyslipidemia (all P < 0.05). Thirdly, ACE2 SNP rs2074192 and rs879922 were associated with carotid arteriosclerosis stenosis (CAS) ≥ 50% (both P < 0.05). Fourthly, ACE2 SNP rs2074192, rs4240157, rs4646188 and 879922 were associated with increased MAU (all P < 0.05). In addition, ACE2 SNP rs2048683, rs4240157, rs4646156, rs4646188 and rs879922 were linked to heavier LVMI (all P < 0.05), but only rs4240157, rs4646156 and rs4646188 were associated with lower LVEF (all P < 0.05). ACE2 SNP rs879922 may be a common genetic loci and optimal genetic susceptibility marker for T2D and T2D related cardiovascular risks in Uygurs.

Cardiovascular benefits by reversing environmental risks factors for essential hypertension (EH) and dyslipidemia could be weaken by high genetic risk. We investigated possible associations between ACE2 polymorphisms and dyslipidemia in patients with EH. Four hundred and two hypertensive patients were enrolled in an EH group and 233 normotensive individuals were enrolled as control group from the Xinjiang region of China. Fourteen ACE2 polymorphisms were genotyped by Matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Participants carrying T allele (TT + CT) of rs2074192 (P = 0.006), rs4646155 (P = 0.030) and rs4646188 (P < 0.001), C allele (CT + CT or CC + CG) of rs4240157 (P = 0.012), rs4830542 (P = 0.020) and rs879922 (P < 0.001) and TT genotype of rs2106809 (P = 0.012) were associated with EH. Meanwhile,ACE2 SNPs also exhibited association with dyslipidemia but exhibited obvious heterogeneity. rs1978124 (TT + CT, P = 0.009), rs2106809 (TT, P = 0.045), rs233575 (CC + CT, P = 0.018), rs4646188 (CC, P = 0.011) and rs879922 (CC + CG, P = 0.003) were association with increased LDL-C (≥1.8 mmol/L). rs2106809 (CC + CT, P < 0.001), rs2285666(TT + CT, P = 0.017), rs4646142(CC + CG, P = 0.044), rs4646155(TT + CT, P < 0.001) and rs4646188(TT + CT, P = 0.033) were association with decreased HDL-C (< 1.0 mmol/L). rs2074192 (TT + CT, P = 0.012), rs4240157 (CC + CT, P = 0.027), rs4646156 (AA+AT, P = 0.007), rs4646188 (TT + CT, P = 0.005), rs4830542 (CC + CT, P = 0.047) and rs879922 (CC + CG, P = 0.001) were association with increased TC (≥5.2 mmol/L). rs2106809 (P = 0.034) and rs4646188 (P = 0.013) were associated with hypertriglyceridemia. Further, ischemic stroke was more prevalent with rs4240157 (CC + CT, P = 0.043), rs4646188 (CC + CT, P = 0.013) and rs4830542 (CC + CT, P = 0.037). In addition, rs2048683 and rs6632677 were not association with EH, dyslipidemia and ischemic stroke. The ACE2 rs4646188 variant may be a potential and optimal genetic susceptibility marker for EH, dyslipidemia and its related ischemic stroke.

Vigorous CD8⁺ T cells play a crucial role in recognizing tumor cells and combating solid tumors. How T cells efficiently recognize and target tumor antigens, and how they maintain the activity in the “rejection” of solid tumor microenvironment, are major concerns. Recent advances in understanding of the immunological trajectory and lifespan of CD8⁺ T cells have provided guidance for the design of more optimal anti-tumor immunotherapy regimens. Here, we review the newly discovered methods to enhance the function of CD8⁺ T cells against solid tumors, focusing on optimizing T cell receptor (TCR) expression, improving antigen recognition by engineered T cells, enhancing signal transduction of the TCR-CD3 complex, inducing the homing of polyclonal functional T cells to tumors, reversing T cell exhaustion under chronic antigen stimulation, and reprogramming the energy and metabolic pathways of T cells. We also discuss how to participate in the epigenetic changes of CD8⁺ T cells to regulate two key indicators of anti-tumor responses, namely effectiveness and persistence.

Background: Cardiovascular death (CVD) in breast cancer patients without chemotherapy (CT) or (and) radiotherapy (RT) has not been studied yet. This study evaluates the correlation between breast cancer and CVD risk independent of chemotherapy or (and) radiotherapy.Methods: Data of female breast cancer patients without receiving CT or RT were retrieved from the Surveillance, Epidemiology, and End Result (SEER) database (2004–2015). Data were divided into two cohorts: tumor resection cohort and no resection cohort. The CVD risk in patients was expressed as standardized mortality ratios (SMRs). A 1:1 propensity score matching (PSM) was applied to balance inter-group bias, and competing risk regressions were utilized to evaluate the impact of tumor resection on CVD.Results: The CVD risk was significantly higher (SMR = 2.196, 95% CI: 2.148–2.245, P<0.001) in breast cancer patients who did not receive CT or RT compared to the general population. Breast cancer patients without tumor resection showed higher CVD risk than patients who underwent tumour resection (tumor resection SMR = 2.031, 95% CI: 1.983–2.079, P<0.001; no resection SMR = 5.425, 95% CI: 5.087–5.781, P<0.001). After PSM, the CVD risk among patients without tumor resection indicated an increase of 1.165-fold compared to patients with tumor resection (HR=1.165, 95% CI: 1.039–1.306, P=0.009).Conclusions: Female breast cancer patients are at higher risk of CVD despite unexposure to cardio-toxic CT or RT. However, female breast cancer patients subjected to tumor resection have decreased CVD risk. These results indicated that monitoring female breast cancer patients not receiving RT or CT might serve as a preventative measure against CVD.