Protective Effect of Nicorandil on Contrast-Induced Acute Kidney Injury After Emergency Percutaneous Coronary Intervention.

Objective: To investigate the protective effect of nicorandil on contrast-induced acute kidney injury (CIAKI) in patients with acute ST-segment elevation myocardial infarction (STEMI) after emergency percutaneous coronary intervention (PCI). Methods: This is a single-center, retrospective control study. A total of 156 patients with STEMI were divided into the nicorandil group (n = 55) and the control group (n = 101). The incidence of CIAKI, defined as an increase of >25% or absolute values > 44.2 µmol/L in serum creatinine (Scr) from baseline within 72 h of exposure to a contrast agent after exclusion of other causes, was the primary endpoint. The secondary endpoints were: (1) changes of Scr, estimated glomerular filtration rate (eGFR), uric acid, and ß2-microglobulin at 24/48/72 h and 5 to 7 days after PCI; (2) the peak value difference of creatine kinase isoenzymes (CK-MB) after PCI; (3) adverse events within 6 months after PCI. Results: The overall incidence of CIAKI was 21.8%; the incidence of CIAKI in the nicorandil group was significantly lower (12.7% [7/55]) than in the control group (26.7% [27/101]) (P = .043). Compared with the control group, Scr, uric acid, and ß2-microglobulin levels were lower, and the level of eGFR was higher in nicorandil group (P all < .05). The peak value of CK-MB in the nicorandil group was lower than that in the control group (105.30 [56.61, 232.04] vs 178.00 [77.08, 271.91]U/L, P = .042). There was no significant difference in adverse events between the 2 groups within 6 months after PCI. Moreover, multivariate logistic regression analysis showed that hypertension and diabetes were independent risk factors for CIAKI, while nicorandil treatment was a protective factor. Conclusion: Our data suggest that intravenous nicorandil after emergency PCI has a protective effect on the occurrence of CIAKI in STEMI patients.

Sex-specific differences in the effect of the atherogenic index of plasma on prediabetes and diabetes in the NHANES 2011-2018 population.

BACKGROUND: Although a great deal of scientific evidence on the epidemiological risk factors for diabetes and prediabetes has been accumulated, there is still insufficient evidence to explore sex-related differences. The aim of this study was to examine sex-specific differences in the effect of the atherogenic index of plasma (AIP) on prediabetes and diabetes. METHODS: This cross-sectional study included data from 10099 American adults. The exposure variable was the AIP, which was defined as log10 (triglycerides/high-density lipoprotein cholesterol). The outcome variables included prediabetes and diabetes defined by the 2013 American Diabetes Association guidelines. RESULTS: The median age (mean ± SD) was 48.51 ± 18.42 years, and the average value (SD) of the AIP was - 0.09 (0.34). The prevalence of prediabetes was 40.24%, and that of diabetes was 21.32%. Overall, there was a significant positive association between the AIP and prediabetes and diabetes (per 1-unit increment in the AIP: OR, 2.49; 95% CI 1.75, 3.54). The multivariate logistic regression model demonstrated that for each unit increment in the AIP, the prediabetes and diabetes prevalence increased 4.96-fold among female participants (OR 4.96, 95% CI 2.68, 9.18) but not among male participants. We found that the AIP was not related to the prevalence of prediabetes or diabetes (OR 1.41; 95% CI 0.87, 2.29) among males. There was an interaction between sex and the AIP (P for interaction < 0.0001). CONCLUSIONS: This study showed that a higher AIP was significantly associated with an increased prevalence of prediabetes and diabetes, and the above relationships occurred only among women and not men.

Plasma exosomes induce inflammatory immune response in patients with acute myocardial infarction.

Exosomes are a kind of nanoscale extracellular vesicles with diameters of 30-100 nm and act as intracellular communication vehicles to influence cellular activities. Emerging pieces of evidence have indicated that exosomes play important roles in inflammation. However, the biological roles of plasma exosomes in acute myocardial infarction (AMI) patients have remained largely unexplored. In the current study, we found the plasma exosome levels were notably increased in patients with AMI in comparison with healthy controls (HCs), and AMI exosomes could induce endothelial cell injury. Furthermore, our data demonstrated that AMI exosomes triggered a pro-inflammatory immune response, at least partly depending on the activation of the NF-ĸB signalling. Together, AMI exosomes have pro-inflammatory properties and play a significant role in inflammation in AMI patients.

MiR-27a-3p targets USP46 to inhibit the cell proliferation of hepatocellular carcinoma.

Micro-RNAs are involved in the occurrence and development of hepatocellular carcinoma (HCC) as potential therapeutic targets for HCC. In this study, we found that miR-27a-3p was highly expressed in HCC, which was associated with lower survival rates of HCC patients. In vivo and in vitro functional experiments confirmed that over-expression or knock-down miR-27a-3p could significantly affect the proliferation ability of HCCLM3 and Huh-7, two HCC cell lines. Ubiquitin-specific protease 46 (USP46) was confirmed as the key target gene of miR-27a-3p in HCC via RNA-seq, quantitative polymerase chain reaction, Western blotting, and luciferase report. When knocking down USP46, the proliferation activity of HCC cells was significantly enhanced, while it was significantly inhibited after over-expressing USP4. Above results suggest that the abnormally over-expressed miR-27a-3p in liver promotes the proliferation of cancer cells and accelerates the development of HCC by targeting inhibition the expression of USP46. Targeting miR-27a-3p may be an effective strategy for prevention and treatment of HCC.

HIF-1α mediates the protective effect of plasma extracellular particles induced by remote ischaemic preconditioning on oxidative stress injury in human umbilical vein endothelial cells.

Remote ischaemic preconditioning (RIPC) is considered to alleviate myocardial ischaemia/reperfusion (I/R) injury. The present study explored whether blood plasma particulate matter, which is termed extracellular particles (EPs), and is released from cells during RIPC, could reduce H2O2-induced damage in human umbilical vein endothelial cells (HUVECs). Firstly, EPs were derived from volunteers who did or did not undergo RIPC. To induce RIPC in volunteers, a blood pressure cuff was alternatively inflated for 5 min and deflated for the same duration for four successive cycles. HUVECs were assigned to two groups: i) Group 1 was preincubated for 24 h with EPs from volunteers after sham-RIPC, then treated with H2O2 (1 mM; 6 h) to mimic the in vivo conditions of I/R-induced oxidative stress; and ii) group 2 was preincubated for 24 h with EPs from volunteers after RIPC, then treated with H2O2. Subsequently, EPs were derived from rats received sham-RIPC or RIPC and/or cadmium (Cd) pre-treatment. To induce RIPC in rats, a remote hind limb preconditioning stimulus was delivered using a blood pressure cuff attached at the inguinal level of the rat. The blood pressure cuff was alternatively inflated for 5 min and deflated for the same time period for four successive cycles. HUVECs were assigned to six groups: i) Group 1 was untreated; ii) group 2 received only H2O2 treatment (1 mM; 6 h); iii) group 3 was preincubated for 24 h with EPs from rats exposed to sham-RIPC, then treated with H2O2; iv) group 4 was preincubated for 24 h with EPs from rats that received an intraperitoneal injection of 1 mg/kg Cd [a pharmacological inhibitor of hypoxia-inducible factor 1-α (HIF-1α) in vivo] 180 min before sham-RIPC, then treated with H2O2; v) group 5 was preincubated for 24 h with EPs from rats exposed to RIPC, then treated with H2O2; and vi) group 6 was preincubated for 24 h with EPs from rats that received an intraperitoneal injection of 1 mg/kg Cd 180 min before RIPC, then treated with H2O2. Cell viability and cytotoxicity were monitored using Cell Counting Kit-8 and lactate dehydrogenase assays. Cell apoptosis and necrosis were assessed via flow cytometry and western blot analysis. A notable increase in EP concentration in the plasma of volunteers after RIPC compared with that in the plasma of volunteers after sham-RIPC was observed. RIPC-associated EPs (RIPC-EPs) from volunteers could improve cell viability and reduce cytotoxicity, cell apoptosis and necrosis in HUVECs treated with H2O2 in vitro. Furthermore, RIPC caused a significant increase in HIF-1α expression in the rat limb musculature. The apoptosis-reducing effect of RIPC-EPs was demonstrated to be counteracted by an intraperitoneal injection of Cd before RIPC in rats. A significant decrease in the EP levels precipitated from the plasma of rats that received Cd treatment before RIPC was observed compared with rats that did not receive Cd treatment. The present study suggested that HIF-1α mediated at least partly the protective effect of plasma RIPC-EPs on oxidative stress injury in HUVECs.

[Clinical observation of refined moxibustion for sequelae of pelvic inflammatory disease with qi stagnation and blood stasis].

OBJECTIVE: To compare the curative effect of refined moxibustion, traditional moxa box moxibustion and Chinese patent medicine on the sequelae of pelvic inflammatory disease with qi stagnation and blood stasis. METHODS: A total of 150 patients with sequelae of pelvic inflammatory disease with qi stagnation and blood stasis were randomized into a refined moxibustion group (50 cases), a box-moxibustion group (50 cases) and a Chinese medication group (50 cases, 2 cases dropped off). The patients in the refined moxibustion group were treated with refined moxibustion at Qihai (CV 6), Guanyuan (CV 4), Zigong (EX-CA 1) and Shuidao (ST 28), 2 moxa-cones for each acupoint. The patients in the box-moxibustion group were treated with box-moxibustion on the lower abdomen and Shenque (CV 8), and the patients in the Chinese medication group were treated with penyanqing capsules orally. All groups started treatment after menstruation, moxibustion was applied once every 4 days, twice a week, and medication was taken 3 times a day for a total of 2 menstrual cycles. The TCM symptoms and body signs scores of each group were observed before and after treatment. The short form health survey (SF-36) scores of each group were observed before and after treatment and during follow-up 12 weeks after treatment. RESULTS: After treatment, the TCM symptoms, body signs and comprehensive scores of each group were lower than those before treatment (P<0.05), and those in the refined moxibustion group were lower than the box-moxibustion group and the Chinese medication group (P<0.05). The SF-36 scores of each group after treatment and during follow-up were higher than before treatment (P<0.05); during follow-up, the SF-36 scores of the box-moxibustion group and the Chinese medication group were lower than after treatment (P<0.05), while that in the refined moxibustion group was higher than after treatment (P<0.05); the SF-36 scores after treatment and during follow-up in the refined moxibustion group were higher than the box-moxibustion group and the Chinese medication group (P<0.05, P<0.01). CONCLUSION: Compared with traditional moxa box moxibustion and Chinese patent medicine treatment, refined moxibustion can better improve the symptoms, body signs and quality of life in patients with the sequelae of pelvic inflammatory disease of qi stagnation and blood stasis, and the effect is longer.

Association between Age at Menarche and Hypertension among Females in Southern China: A Cross-Sectional Study.

BACKGROUND: Association between age at menarche (AAM) and hypertension remains a controversial topic, and data in China were sparse. Therefore, we aimed to investigate the association between AAM and hypertension in Chinese female population. METHODS: In this cross-sectional study, 5,102 females aged ≥15 years were enrolled. Self-reported AAM was assessed by the questionnaire. Multiple linear regression analysis was used to evaluate the association between systolic blood pressure (SBP), diastolic blood pressure (DBP), and AAM. Logistic regression analysis was performed to evaluate the association between hypertension and AAM. Generalized additive model (GAM) and smooth curve fitting (penalized spline method) were conducted to explore the exact shape of curve between them. RESULTS: The overall mean of AAM was 15.5 years. Each additional year of AAM was associated with a 15% higher risk of hypertension (odds ratio (OR) = 1.15, 95% confidence interval (CI): 1.11-1.19). Among females with hypertension, there was a significant positive association between AAM and SBP (ß = 0.88, 95% CI: 0.29-1.46) and DBP (ß = 0.80, 95% CI: 0.47-1.13). A significantly higher risk of hypertension was found in younger subjects (15-44 y: OR = 1.37, 95% CI: 1.21-1.55; P for interaction = 0.009) compared with those aged between 62 and 97 y. CONCLUSIONS: AAM was positively associated with hypertension and blood pressure, especially among females in early adulthood from southern China.

Peripheral leukocyte count and risk of bleeding in patients with non-valvular atrial fibrillation taking dabigatran: a real-world study.

BACKGROUND: The association between peripheral leukocyte count and bleeding events in nonvalvular atrial fibrillation (NVAF) patients treated with dabigatran remains unclear. This study aimed to explore the association between leukocyte count and bleeding events after excluding other confounders in NVAF patients taking dabigatran. METHODS: A total of 851 NVAF patients treated with dabigatran (110 mg bid) were recruited from 12 centers in China from February 2015 to December 2017. Follow-up was completed by May 2018. The exposure and outcome variables were leukocyte count measured at baseline and the number of bleeding events within the subsequent 6 months. Multivariate Cox proportional hazards models were constructed to analyze independent associations, and a Cox proportional hazards regression with cubic spline functions and smooth curve fitting (penalized spline method) was used to address nonlinearity between leukocyte count and bleeding. The inflection point was calculated using a recursive algorithm, and then a two-piecewise Cox proportional hazards model for both sides of the inflection point was constructed. RESULTS: During 6-month follow-up, 87 participants occurred bleeding events. For every 1 × 10/L increase in leukocyte count, the risk of bleeding increased by 11% (hazard ratio [HR]: 1.11, 95% confidence interval [CI]: 0.99-1.25). The smooth curve showed nonlinear relationship between leukocyte count and bleeding events. The inflection point of the leukocyte count was 6.75 × 10/L. For leukocyte counts < 6.75 × 10/L, the HR (95% CI) was 0.88 (0.69-1.13), and for leukocyte counts ≥ 6.75 × 10/L, the HR (95% CI) was 1.28 (1.09-1.51). CONCLUSION: This study found a J-shaped association between baseline leukocyte count and risk of bleeding in NVAF patients treated with dabigatran. CLINICAL TRIAL REGISTRATION: NCT02414035, https://clinicaltrials.gov.

HSP22 suppresses diabetes-induced endothelial injury by inhibiting mitochondrial reactive oxygen species formation.

The induction of mitochondrial reactive oxygen species (mtROS) by hyperglycemia is a key event responsible for endothelial activation and injury. Heat shock protein 22 (HSP22) is a stress-inducible protein associated with cytoprotection and apoptosis inhibition. However, whether HSP22 prevents hyperglycemia-induced vascular endothelial injury remains unclear. Here, we investigated whether HSP22 protects the vascular endothelium from hyperglycemia-induced injury by reducing mtROS production. We used a high-fat diet and streptozotocin injection model to induce type 2 diabetes mellitus (T2DM, metabolic syndrome) and exposed human umbilical vein endothelial cells (HUVECs) to high glucose following overexpression or silencing of HSP22 to explore the role of HSP22. We found that HSP22 markedly inhibited endothelial cell activation and vascular lesions by inhibiting endothelial adhesion and decreasing cytokine secretion. We performed confocal microscopy and flow cytometry assays using HUVECs and showed that HSP22 attenuated mtROS and mitochondrial dysfunction in hyperglycemia-stimulated endothelial cells. Mechanistically, using the mtROS inhibitor MitoTEMPO, we demonstrated that HSP22 suppressed endothelial activation and injury by eliminating hyperglycemia-mediated increases in mtROS. Furthermore, we found that HSP22 maintained the balance of mitochondrial fusion and fission by mitigating mtROS in vitro. HSP22 attenuated the development of vascular lesions by suppressing mtROS-mediated endothelial activation in a T2DM mouse model. This study provides evidence that HSP22 may be a promising therapeutic target for vascular complications in T2DM.