The effect of health coaching on blood pressure control and disease self-management among patients in rural area in China: a randomized controlled trial.

The self-management education for patients with hypertension has not been widely provided in rural areas of China. Our study aimed to examine the effect of health coaching intervention on controlling BP and improving self-management skills among rural resident of ≤6 month-history of hypertension. A total of 102 participants were enrolled in the RCT. The control group received usual health guidance and follow-up management; the experimental group received health coaching and follow up management. The primary outcomes were the difference in changes of BP and mean self-management scores. The secondary outcomes included waist circumference, body mass index (BMI), and medication literacy. Participants in the experimental group showed a significantly greater improvement with respect to systolic BP and diastolic BP respectively (133.85 ± 4.74 mmHg vs 127.96 ± 5.42 mmHg;80.94 ± 5.52 mmHg vs 77.37 ± 4.44 mmHg, P < 0.05) and BMI (24.66 ± 2.19 kg/m2 vs 23.44 ± 2.05 kg/m2, P < 0.05) compared with the control group. A significant difference was also observed between the experimental and control groups in terms of self-management and medication literacy at both 3 and 6 months (P < 0.05). However, there was no significant difference in changes of waist circumferences between the two groups (22.6% vs 38.8%). In conclusion, for patients with diagnosed with hypertension within the last 6 months, health coaching maybe is an effective approach to control blood pressure and improve medication literacy and self-management skills.

Initial treatment with a single capsule containing half-dose quadruple therapy vs standard-dose dual therapy in hypertensive patients (QUADUAL): Study protocol for a randomized, blinded, crossover trial.

BACKGROUND: Combined antihypertensive therapy has obvious advantages over single drug therapy. Hypertension guidelines fully affirm the efficacy of dual combination in initial antihypertensive therapy. Recent studies have also pointed out that the quadruple combination of very low-dose antihypertensive drugs is superior to single drugs. However, whether low-dose quadruple therapy is better than dual combination is unknown. OBJECTIVE: To evaluate and compare the efficacy and safety of half-dose quadruple therapy vs standard-dose dual therapy in the initial treatment of hypertensive patients with systolic/diastolic blood pressure 140-179/90-109 mm Hg. METHODS: A randomized double-blind crossover clinical trial will be conducted to compare the efficacy and safety of low-dose quadruple antihypertensives (irbesartan 75 mg + metoprolol 23.75 mg + amlodipine 2.5 mg + indapamide 1.25 mg) with standard-dose dual antihypertensives (irbesartan 150 mg + amlodipine 5 mg) in the initial treatment of patients with mild to moderate hypertension (140-179/90-109 mm Hg). Ninety patients are required and will be recruited and randomly assigned in a 1:1 ratio to 2 crossover groups. Two groups will receive a different combination therapy for 4 weeks, then switch to the other combination therapy for 4 weeks, with a 2-week wash-out. The patients will be followed up for 4 weeks to compare the antihypertensive effects and related adverse effects of the 2 antihypertensive combination treatments. CONCLUSIONS: We present the rationale for the design of the QUADUAL trial. The trial started in July 2022 and is expected to be completed by August 2023. The study aims to evaluate if an initial treatment regimen of quadruple combination of half-dose blood pressure medications will result in greater reduction in blood pressure and fewer side effects compared to standard dose dual therapy. REGISTRATION: www. CLINICALTRIALS: gov (NCT05377203).

Sympathetic nerve innervation and metabolism in ischemic myocardium in response to remote ischemic perconditioning.

Sympathetic nerve denervation after myocardial infarction (MI) predicts risk of sudden cardiac death. Therefore, therapeutic approaches limit infarct size, improving adverse remodeling and restores sympathetic innervation have a great clinical potential. Remote ischemic perconditioning (RIPerc) could markedly attenuate MI-reperfusion (MIR) injury. In this study, we aimed to assess its effects on cardiac sympathetic innervation and metabolism. Transient myocardial ischemia is induced by ligature of the left anterior descending coronary artery (LAD) in male Sprague-Dawley rats, and in vivo cardiac 2-[18F]FDG and [11C]mHED PET scans were performed at 14-15 days after ischemia. RIPerc was induced by three cycles of 5-min-long unilateral hind limb ischemia and intermittent 5 min of reperfusion during LAD occlusion period. The PET quantitative parameters were quantified in parametric polar maps. This standardized format facilitates the regional radioactive quantification in deficit regions to remote areas. The ex vivo radionuclide distribution was additionally identified using autoradiography. Myocardial neuron density (tyrosine hydroxylase positive staining) and chondroitin sulfate proteoglycans (CSPG, inhibiting neuron regeneration) expression were assessed by immunohistochemistry. There was no significant difference in the mean hypometabolism 2-[18F]FDG uptake ratio (44.6 ± 4.8% vs. 45.4 ± 4.4%) between MIR rats and MIR + RIPerc rats (P > 0.05). However, the mean [11C]mHED nervous activity of denervated myocardium was significantly elevated in MIR + RIPerc rats compared to the MIR rats (35.9 ± 7.1% vs. 28.9 ± 2.3%, P < 0.05), coupled with reduced denervated myocardium area (19.5 ± 5.3% vs. 27.8 ± 6.6%, P < 0.05), which were associated with preserved left-ventricular systolic function, a less reduction in neuron density, and a significant reduction in CSPG and CD68 expression in the myocardium. RIPerc presented a positive effect on cardiac sympathetic-nerve innervation following ischemia, but showed no significant effect on myocardial metabolism.

Imaging Inflammation in Atherosclerosis with CXCR4-Directed [68Ga]PentixaFor PET/MRI-Compared with [18F]FDG PET/MRI.

(1) This study compared [68Ga]PentixaFor uptake in active arterial segments with corresponding [18F]FDG arterial uptake as well as the relationship with cardiac [68Ga]PentixaFor uptake. (2) Method: Tracer uptake on atherosclerotic lesions in the large arteries was measured and target-to-background ratios (TBR) were calculated to adjust background signals with two investigators blinded to the other PET scan. On a patient-based and lesion-to-lesion analysis, TBR values of two tracers were compared and the relationship with cardiac inflammation was further explored. Furthermore, two cardiovascular risk-related groups were divided to explore the value of risk stratification of the two tracers in atherosclerosis. (3) Results: [68Ga]PentixaFor PET/MRI identified more lesions (88% vs. 48%; p < 0.001) and showed higher uptake than [18F]FDG PET/MRI (TBR, 1.90 ± 0.36 vs. 1.63 ± 0.29; p < 0.001). In the patient-based analysis, the TBR of [68Ga]PentixaFor uptake was also significantly higher than [18F]FDG uptake (1.85 ± 0.20 vs. 1.42 ± 0.19; p < 0.001). The TBR of active lesions for [68Ga]PentixaFor was significantly increased in the high-risk group (n = 9), as compared to the low-risk group (n = 10) (2.02 ± 0.15 vs. 1.86 ± 0.10, p = 0.015), but not for [18F]FDG (1.85 ± 0.10 vs. 1.80 ± 0.07, p = 0.149). (4) Conclusion: [68Ga]PentixaFor PET/MRI identified many more lesions than [18F]FDG PET/MRI. Patients with high-risk cardiovascular factors illustrated an increased uptake of [68Ga]PentixaFor. There was a correlation between the elevated uptake of [68Ga]PentixaFor in the active arterial segments and heart.

The effect of heart rate on blood pressure measurement in patients with atrial fibrillation: a cross-sectional study.

This study explored the effect of heart rate (HR) on the stability and accuracy of blood pressure (BP) measurement and the optimal HR range for the most accurate blood pressure measurement in atrial fibrillation (AF) patients. A total of 583 patients (383 and 200 with AF and sinus rhythm (SR), respectively) were included in this study. The noninvasive blood pressure (NIBP), invasive blood pressure (IBP), and HR were repeatedly measured ten times at 30-second intervals for every patient. Both the AF and SR groups were then subdivided into five groups depending on the HR (i.e., < 60, 60-80, 80-100, 100-120, and ≥120 bpm). The difference between the IBP and NIBP (i.e., △SBP) and the coefficient of variation (CV) were calculated, and the stability and accuracy of NIBP measurements were analyzed. CV and △SBP were significantly higher in the AF group. In the AF group, the CV of NIBP was highest when the HR was ≥ 100 bpm; and △SBP was significantly lower in the HR groups with 60-80 and 80-100 bpm (< 60 bpm, △SBP 11.62 ± 2.64 mmHg; 60-80 bpm, △SBP 7.10 ± 1.92 mmHg; 80-100 bpm, △SBP 7.10 ± 2.95 mmHg; 100-120 bpm, △SBP 10.52 ± 2.72 mmHg; ≥120 bpm, △SBP 14.15 ± 3.61 mmHg, P < 0.05). The stability and accuracy of the NIBP in the SR groups were not affected by the HR. In AF patients, the NIBP stability was low when the HR was high, and the NIBP was often underestimated when the HR was high or low. Sixty to 100 bpm is the best HR range for measuring blood pressure in AF patients.

Feasibility of In Vivo Imaging of Fibroblast Activation Protein in Human Arterial Walls.

Increased expression of fibroblast-activating protein (FAP) in fibrous caps may contribute to progression of atherosclerotic plaques. Methods: Forty-one patients who underwent 68Ga-conjugated quinoline-based FAP inhibitor (68Ga-FAPI-04) PET/CT for noncardiovascular indications were retrospectively analyzed. Correlations were assessed between the uptake of 68Ga-FAPI-04 in large arterial walls (SUVmax and target-to-background ratio, TBR) and degree of calcification and cardiovascular risk factors. Results: Focal arterial uptake of 68Ga-FAPI-04 or calcification was detected in 1,177 arterial segments in all 41 patients. TBR was negatively correlated with the degree of calcification (Hounsfield units) (r = -0.27, P < 0.01). Mean TBR in higher-risk patients was greater than in lower-risk patients (2.2 ± 0.3 vs. 1.8 ± 0.3, P < 0.01). Immunohistochemical labeling of carotid plaques exhibited prominent FAP expression in a thin fibrous cap and moderate FAP expression in a thick cap. Conclusion:68Ga-FAPI-04 PET/CT might have potential for imaging fibroblastic activation in the arterial wall.

Genotype-Guided Dosing of Warfarin in Chinese Adults: A Multicenter Randomized Clinical Trial.

BACKGROUND: Warfarin is an effective treatment for thromboembolic disease but has a narrow therapeutic index; optimal anticoagulation dosage can differ tremendously among individuals. We aimed to evaluate whether genotype-guided warfarin dosing is superior to routine clinical dosing for the outcomes of interest in Chinese patients. METHODS: We conducted a multicenter, randomized, single-blind, parallel-controlled trial from September 2014 to April 2017 in 15 hospitals in China. Eligible patients were ≥18 years of age, with atrial fibrillation or deep vein thrombosis without previous treatment of warfarin or a bleeding disorder. Nine follow-up visits were performed during the 12-week study period. The primary outcome measure was the percentage of time in the therapeutic range of the international normalized ratio during the first 12 weeks after starting warfarin therapy. RESULTS: A total of 660 participants were enrolled and randomly assigned to a genotype-guided dosing group or a control group under standard dosing. The genotype-guided dosing group had a significantly higher percentage of time in the therapeutic range than the control group (58.8% versus 53.2% [95% CI of group difference, 1.1-10.2]; P=0.01). The genotype-guided dosing group also achieved the target international normalized ratio sooner than the control group. In subgroup analyses, warfarin normal sensitivity group had an even higher percentage of time in the therapeutic range during the first 12 weeks compared with the control group (60.8% versus 48.9% [95% CI, 1.1-24.4]). The incidence of adverse events was low in both groups. CONCLUSIONS: The outcomes of genotype-guided warfarin dosing were superior to those of clinical standard dosing. These findings raise the prospect of precision warfarin treatment in China. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02211326.

[Aortic valve degenerative disease with patent ductus arteriosus infective endocarditis: A case report].

OBJECTIVE: Infective endocarditis (IE) refers to the pathogenic microbial infect the endocardium, valves or intima adjacent to the cardiac arteries through the bloodstream with the formation of vegetations. Valves are the most frequently affected sites. Here, we described a 49-year-old female, who admitted to respiratory outpatient department in the Third Xiangya Hospital, Central South University for long time of fever. Chest computer tomography (CT) found a thick wall cavity in the apex of the right lung with smooth wall and fluid plane, without enhancement, which was considered as inflammation and tuberculosis to be excluded. Echocardiography showed vegetations on the aortic valve, where abscess was found on the root. Accidentally in surgery, a patent ductus arteriosus (PDA) was found. The surgeon closed the PDA and performed aortic valve prosthetic valve replacement. Bacterial colony of coccus was found in the pathological tissue, which was consistent with the diagnosis of valvular degeneration with infection. Lung lesion was obviously absorbed after 6 weeks of treatment with vancomycin, which has been confirmed as a sensitive antibacterial drug to Enterococcus faecalis. Overall, the pulmonary lesion was caused by the detachment of bacterial neoplasm of aortic valve, which has passed through the PDA and entered the pulmonary circulation.

Effects of genetic variants in UGT1A1, SLCO1B3, ABCB1, ABCC2, ABCG2, ORM1 on PK/PD of telmisartan in Chinese patients with mild to moderate essential hypertension
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PURPOSE: This study aimed to understand the effects of single nucleotide polymorphisms (SNPs) in UGT1A1, SLCO1B3, ABCB1, ABCC2, ABCG2, and ORM1 on the pharmacokinetics (PK) (plasma concentration) and pharmacodynamics (PD) (blood pressure) of telmisartan in Chinese patients. METHODS: 58 Han Chinese patients (aged 45 - 72 years) with mild to moderate essential hypertension were included and received 80 mg/day telmisartan for 4 weeks. The plasma concentration and genetic variants were determined by LC/MS/MS and MALDI-TOF mass spectrometry, respectively. Multivariable linear analysis was used to examine the relationships between PK/PD and genetic variants. RESULTS: Females showed a significantly higher AUClast than males (n = 22, 4,879.48 ± 3,449.33 h×ng/mL vs. n = 36, 2,715.59 ± 2,223.77 h×ng/mL, p = 0.047). Amongst all genetic variants investigated, the patients with UGT1A1 rs4124874 AA (n = 11, 1,730.51 ± 1,325.79 h×ng/mL) had a significantly lower AUClast compared with patients with UGT1A1 rs4124874 CC+AC (n = 19 + 28, 4,177.44 ± 3,222.11 h×ng/mL and 3,810.82 ± 2,960.43 h×ng/mL, p = 0.027). None of the SNPs investigated was associated with the PD responses to telmisartan. CONCLUSION: Variation of UGT1A1 (rs4124874) affects PK of telmisartan in Chinese patients, highlighting the value of genetic testing in precision medicine as the telmisartan dose could be adjusted based on UGT1A1 genetic variations.
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Low-intensity pulsed ultrasound upregulates pro-myelination indicators of Schwann cells enhanced by co-culture with adipose-derived stem cells.

OBJECTIVES: Peripheral nerve injuries are a common occurrence, resulting in considerable patient suffering; it also represents a major economic burden on society. To improve treatment options following peripheral nerve injuries, scientists aim to find a way to promote Schwann cell (SC) myelination to help nerves to carry out their functions effectively. In this study, we investigated myelination ability of SCs, regulated by co-culture with adipose-derived stem cells (ASCs) or low-intensity pulsed ultrasound (LIPUS), and synergistic effects of combined treatments. MATERIALS AND METHODS: Schwann cells were co-cultured with or without ASCs, and either left untreated or treated with LIPUS for 10 min/d for 1, 4 or 7 days. Effects of LIPUS and ASC co-culture on pro-myelination indicators of SCs were analysed by real-time PCR (RT-PCR), Western blotting and immunofluorescence staining (IF). RESULTS: Our results indicate that ASC-SC co-culture and LIPUS, together or individually, promoted mRNA levels of epidermal growth factor receptor 3 (EGFR3/ErbB3), neuregulin1 (NRG1), early growth response protein 2 (Egr2/Krox20) and myelin basic protein (MBP), with corresponding increases in protein levels of ErbB3, NRG1 and Krox20. Interestingly, combination of ASC-SC co-culture and LIPUS displayed the most remarkable effects. CONCLUSION: We demonstrated that ASCs upregulated pro-myelination indicators of SCs by indirect contact (through co-culture) and that effects could be potentiated by LIPUS. We conclude that LIPUS, as a mechanical stress, may have potential in nerve regeneration with potential clinical relevance.

Population pharmacokinetics study of dexmedetomidine in Chinese adult patients during spinal anesthesia.

OBJECTIVES: The objectives of this study were to construct a population pharmacokinetics model for dexmedetomidine used in Chinese adult patients with spinal anesthesia and to identify the key factors affecting the pharmacokinetics of dexmedetomidine. METHODS: A total of 34 subjects (elderly group: n = 15; young group: n = 19) undergoing spinal anesthesia received dexmedetomidine with a loading dose of 0.5 µg×kg(-1) for 10 minutes, followed by a maintenance dose of 0.5 µg×kg-1×h(-1) for 50 minutes. Blood samples were collected until 10 hours after dosing. Laboratory and respiratory parameters, and dexmedetomidine concentrations were measured. A population pharmacokinetic model for dexmedetomidine was constructed using a nonlinear mixed effects model (NONMEM). RESULTS: Pharmacokinetics of dexmedetomidine can be described by a three-compartment model. The respective typical values for clearance (CL), V1, V2, Q2, Q3, and V3 were 0.883 L×min(-1), 17.6 L, 51.5 L, 2.37 L×min(-1), 0.517 L×min(-1), and 44.00 L. Alanine aminotransferase (ALT), age, and body weight were key factors affecting CL, V1, and V2, respectively. CONCLUSIONS: A three-compartment model can be used to describe the pharmacokinetics processing of dexmedetomidine for Chinese adult patients during spinal anesthesia. The population pharmacokinetic of dexmedetomidine was generally in line with results from previous studies.

[Manifestation, distribution of pathogen, and resistance of bloodstream infections after renal transplantation: clinical analysis of 71 patients].

OBJECTIVE: To investigate the clinical manifestation and determine the distribution of pathogens and their characteristics of drug susceptibility to bloodstream infections (BSIs), and provide evidence for clinical anti-infection treatments after renal transplantation. METHODS: Totally 81 episodes of BSIs occurred in 71 patients between July 2003 and June 2013. We retrospectively analyzed the pathogens and their drug susceptibility characteristics with BD microbiological assay system. We also collected the clinical and laboratory data of the patients . RESULTS: The main pathogens were gram negative bacteria (67.90%), followed by gram positive bacteria (28.40%) and fungi (3.70%). The most common gram negative bacillus was Escherichia coli. While for gram positive bacteria, the main bacillus was coagulase-negative staphylococci. The gram negative bacteria were relatively sensitive to aminoglycosides and carbapenem. The gram positive bacteria were sensitive to glycopeptides and oxazolidone. CONCLUSION: The clinical manifestations included high body temperature, onset in the early period after kidney transplantation and high mortality. Though gram positive coccus plays an important role, most infections are caused by gram negative bacteria in BSIs after the renal transplantation. The antibiotic resistant rate for gram negative bacteria is very high as well as gram positive bacteria.

[Roles of periostin in proliferation and migration of vascular smooth muscle cells and the effect of atorvastatin on them].

OBJECTIVE: To investigate the expression of periostin in in vitro cultured vascular smooth muscle cells (VSMCs) induced by TGF-ß1 and the relationship between periostin expression and the migration and proliferation of the VSMCs. Further, to investigate the effects of atorvastatin on the above-mentioned processes and the molecular mechanisms of atorvastatin inhibition of TGF-ß1- induced periostin production. METHODS: Rat aorta smooth muscle cells were cultivated by the method of tissue explants adherence. Cells of generation 3 to 6 were used as the experimental system. Primary cultured rat vascular smooth muscle cells were treated by TGF-ß1 and different concentrations of atorvastatin,Y-2763 (Rho kinase inhibitor), or atorvastatin plus MVA for 24 hours. The expression of periostin was measured by RT-PCR and Western blot. A Boyden chamber assay was used to measure cell migration, and an MTT test was used to measure cell proliferation. RESULTS: Periostin expression in rat VSMCs stimulated by TGF-ß1 increased significantly (4.158 ± 0.515 vs 0.385 ± 0.031), VSMC migration(25 ± 4 vs 8 ± 2) and proliferation (0.85 ± 0.06 vs 0.32 ± 0.03) also increased significantly. Atorvastatin significantly inhibited TGF-ß1-induced periostin production in rat VSMCs, as well as VSMC migration and proliferation, in a dose-dependent manner. Rho kinase inhibitor Y-27632 significantly inhibited TGF-ß1-induced periostin production in rat VSMCs (2.082 ± 0.245). The inhibitory effect of atorvastatin on periostin upregulation induced by TGF-ß1 was reversed by mevalonate (3.838 ± 0.326). CONCLUSION: Periostin can promote rat VSMC migration and proliferation. Atorvastatin inhibition of periostin expression induced by TGF-ß1 in VSMCs may be exerted by inhibition of the production of MVA and other isoprene compounds and by blocking the Rho/Rho kinase signaling pathway.

[Effect of IL-10 on LOX-1 expression of peripheral blood monocytes in patients with acute coronary syndrome].

OBJECTIVE: To determine the expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) of peripheral blood monocytes in patients with acute coronary syndromes (ACS),and to further explore the effect of anti-inflammatory factor interleukin-10 (IL-10) on the expression of LOX-1. METHODS: Twenty-eight healthy controls and 28 ACS patients were enrolled in the study. The levels of IL-10 and tumor necrosis factor (TNF-alpha) were determined by enzyme-linked immunosorbnent assay(ELISA). The monocytes of peripheral blood in patients and controls were isolated and incubated with exogenous IL-10 (20 microg/L). The expression of LOX-1 protein and mRNA in the monocytes was examined by Western blot and reverse transcriptase PCR (RT-PCR). RESULTS: Compared with the healthy controls, the levels of serum IL-10 and TNF-alpha were significantly elevated in ACS patients (P<0.01). The expression of LOX-1 protein and mRNA was markedly upregulated in the isolated monocytes from ACS patients, which could be downregulated by IL-10 (20 microg/L, 3 h) (P<0.01). CONCLUSION: The effect of anti-inflammatory factor IL-10 on the atherosclerosis may be a new mechanism resulting in plaque stabilization via the decreased LOX-1 expression of peripheral monocytes in ACS patients.

[Proatherogenic effects of immune complexes of human oxLDL in vitro].

OBJECTIVE: To observe the effects of immune complexes (IC) prepared from human oxidized density lipoprotein (oxLDL) antibodies and human oxLDL on the foam cell forming and the macrophage activation, and to further uncover the possible mechanisms of immune complexes contributing to the atherosclerosis occurrence. METHODS: The immune complexes of human oxLDL and purified human oxLDL antibodies were added to culture U937 cells by protocols: polyethylene glycol-precipitated insoluble IC (PEG-IC) and IC immobilized by absorption to red blood cells (RBC-IC). With oxLDL as controls and heat-aggregated gamma globulin as an inhibitor of Fc gamma receptor, we measured the cholesterol ester, total cholesterol of the cellular extracts, and quantified the secreted MMP-1 of supernatants from U937 cells. RESULTS: A significant increase of MMP-1 release [(0.769 +/- 0.030) ng/ml vs (0.513 +/- 0.034) ng/ml, P < 0.01] and a higher level of cholesterol ester accumulation [(20.271 +/- 1.668) microg/mg protein vs (17. 226 +/- 1.298 ) microg/mg protein, P < 0.05] in U937 cells incubated with RBC-IC were observed, compared with those incubated with RBC-oxLDL. However, the above quantative difference between the cholesterol ester accumulation induced by oxLDL and insoluble PEG-IC was even more striking, and cholesterol ester accumulation was dosage-dependent. Heat-aggregated gamma globulin (10 mg/ml) as an inhibitor of Fc gamma receptors competitively inhibited cholesterol ester accumulation and decreased PEG-IC stimulating MMP-1 secretion to 71%. CONCLUSION: Immune complexe of ox-LDL can transform macrophages into foam cells and activted macrophages. The immunological function of oxLDL is involved in the process of atherosclerosis occurrence.