Granzyme B PET imaging inflammation and remodeling in myocardial infarction.

PURPOSE: This study aimed to evaluate whether granzyme B (GzmB)-targeted positron emission tomography (PET) imaging agent (68 Ga-grazytracer) can characterize cardiac inflammation and remodeling in myocardial infarction (MI). METHODS: Rats with MI were subjected to GzmB-targeted PET/CT on post-operative days 1, 3, 6, 14, and 28. Autoradiography, Masson staining, immunohistochemistry, and ELISA were performed to verify the inflammatory response and remodeling after MI in vitro. Rats were treated with GzmB inhibitor Z-IETD-FMK to improve cardiac remodeling. Cardiac function tests were performed by echocardiography at 6 weeks after MI. RESULTS: The highest uptake of 68 Ga-grazytracer was observed on day 3 after MI compared with the values obtained on the other days (0.294 ± 0.03% ID/g at 3 days vs. 0.122 ± 0.01% ID/g in the sham group, P < 0.001). Immunohistochemistry showed significantly high expression of GzmB and CD8, in line with the PET/CT imaging results. Autoradiography revealed 68 Ga-grazytracer accumulation in the infarcted myocardium. The 68 Ga-grazytracer uptake of treated rats was significantly reduced compared with that in the MI groups (0.184 ± 0.03%ID/g vs. 0.286 ± 0.03%ID/g; P < 0.001). Echocardiography showed that the left ventricular ejection fraction was lower in the MI groups than in the ischemia reperfusion group. GzmB inhibitor treatment was shown to be effective in improving cardiac function without significantly shortening infarct size. CONCLUSIONS: This study demonstrated the potential of 68 Ga-grazytracer imaging to delineate adverse inflammatory responses and pathological cardiac remodeling, which can help predict heart function. PET/CT imaging-guided therapy may reduce myocardial injury and improve heart function in MI.

Association between interleg systolic blood pressure difference and apparent peripheral neuropathy in US adults with diabetes: a cross-sectional study.

BACKGROUND: Interleg systolic blood pressure difference (ILSBPD) is associated with peripheral artery disease, but the relationship between ILSBPD and apparent peripheral neuropathy in diabetic patients remains unclear. We explored the relationship between ILSBPD and apparent peripheral neuropathy and examined the possible effect modifiers in US adults with diabetes. METHODS: One thousand and fifty-one diabetic participants were included in the study with complete data on systolic blood pressure of the lower extremities and Semmes-Weinstein 10-g monofilament testing from the 1999-2004 National Health and Nutritional Examination Surveys. Systolic blood pressure in the lower extremities was measured using an oscillometric blood pressure device with the patient in the supine position. Apparent peripheral neuropathy was defined as the presence of monofilament insensitivity. RESULTS: Every 5-mmHg increment in ILSBPD is associated with an about 14% increased risk of apparent peripheral neuropathy in crude model, but after adjustment for covariates, the correlation became nonsignificant (P = 0.160). When participants were divided into groups based on ILSBPD cutoffs of 5, 10 and 15 mmHg in different analyses, there was a significantly increased risk of apparent peripheral neuropathy in the ILSBPD ≥ 15 mmHg group (OR 1.79, 95% CI 1.11-2.91, P = 0.018), even after adjusting for confounders. In subgroup analysis, no interaction effect was found (all P for interaction > 0.05). CONCLUSIONS: In US adults with diabetes, an increase in the ILSBPD (≥ 15 mmHg) was associated with a higher risk of apparent peripheral neuropathy.

Spinal and bulbar muscular atrophy combined with hypertrophic cardiomyopathy and Brugada-pattern electrocardiographic changes: A case report.

Spinal and bulbar muscular atrophy (SBMA) is a rare X-linked recessive neurodegenerative disorder caused by the excessive expansion of cytosine-adenine-guanine repeat sequences in the androgen receptor gene encoded on the Xq11-12 chromosome. SBMA primarily affects adult males and is characterized by weakness and atrophy of the proximal limb muscles, often involving the bulbar muscles. In addition to neuromuscular deficits, nonneuronal symptoms such as hypertension, hyperlipidemia, and liver dysfunction are often observed in patients with SBMA. Previous studies have suggested that SBMA patients have been diagnosed with hypertrophic cardiomyopathy (HCM), while gene detection is lacked. Moreover, according to current reports, SBMA patients can carry Brugada syndrome or HCM respectively, while three kinds of diseases have not been reported to exist in the same patient. Here, we report the first case of a male diagnosed with SBMA combined with HCM and two types of Brugada-pattern electrocardiographic changes, with a heterozygous missense mutation in the TTN gene.

Impact of atrial fibrillation on the accuracy of oscillometric blood pressure monitoring in ICU patients from a large real-world database.

OBJECTIVES: Oscillometric blood pressure (BP) measurement in atrial fibrillation patients is controversial due to stroke volume variation. Here, we performed a cross-sectional study to investigate the impact of atrial fibrillation on the accuracy of oscillometric BP in the ICU setting. METHODS: Adult patients with atrial fibrillation or sinus rhythm records were enrolled from Medical Information Mart for Intensive Care-III database. Concurrently recorded noninvasive oscillometric BPs (NIBPs) and intra-arterial BPs (IBPs) were classified as atrial fibrillation or sinus rhythm group according to heart rhythm. Bland-Altmann plots assessed bias and limits of agreement of NIBP to IBP. Pairwise comparison was performed on NIBP/IBP bias between atrial fibrillation and sinus rhythm. Linear mixed-effect model was used to assess the impact of heart rhythm on NIBP/IBP bias after adjusting confounders. RESULTS: Two thousand, three hundred and thirty-five patients (71.95 ±â€Š11.23 years old, 60.90% were men) were included. Systolic, diastolic, and mean NIBP/IBP biases were not clinically different between atrial fibrillation and sinus rhythm circumstances (SBP bias: 0.66 vs. 1.21 mmHg, P  = 0.002; DBP: -5.29 vs. -5.17, P  = 0.1; mean BP: -4.45 vs. -4.19, P  = 0.01). After adjusting for age, sex, heart rate, arterial BP, and vasopressor usage, the effect of heart rhythm on NIBP/IBP bias was within ±5 mmHg for SBP and DBP [effect on SBP bias: 3.32 mmHg (95% confidence interval (CI) 2.89-3.74), P  < 0.001; DBP: -0.89 (-1.17 to -0.60), P  < 0.001], while the effect on mean BP bias was not significant [0.18 mmHg (-0.10 to 0.46), P  = 0.2]. CONCLUSION: Atrial fibrillation would not influence the agreement of oscillometric BP to IBP in ICU patients compared with sinus rhythm.

Renal denervation in management of heart failure with reduced ejection fraction: A systematic review and meta-analysis.

BACKGROUND: Some, but not all, recent studies have shown that renal denervation (RDN) can improve cardiac function and exercise tolerance in people who have heart failure with reduced ejection fraction (HFrEF). This study assessed the efficacy and safety of RDN as a treatment for HFrEF. METHODS: The Medline, Cochrane Library, Embase, and PubMed databases were searched through to September 28, 2022 for clinical studies that evaluated the effect of RDN on HFrEF. The primary endpoints were changes in left ventricular ejection fraction (LVEF) and 6-min walk distance (6MWD). Secondary endpoints were changes in echocardiographic parameters, including left ventricular end-diastolic and end-systolic diameters, left atrial diameter, and interventricular septal thickness. N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, New York Heart Association (NYHA) class, heart rate, and systolic and diastolic blood pressure were also evaluated. Major adverse events were defined as death and rehospitalization for heart failure during follow-up. The estimated glomerular filtration rate (eGFR) and serum creatinine level were extracted as measures of renal function. RESULTS: Eleven trials comprising 313 patients were eligible for quantitative analysis. Pooled analyses showed a mean increase in LVEF of 4.25 % (95 % CI 1.77-6.72; p < 0.001, I2 = 69 %) and an increase in 6MWD (mean difference 50.28 m, 95 % CI 8.78-91.78; p = 0.02; I2 = 81 %) after RDN. Left ventricular end-diastolic and end-systolic diameters, left atrial diameter, and interventricular septal thickness also improved after RDN. NT-proBNP, NYHA class, and heart rate were significantly decreased after RDN. There were no significant changes in blood pressure after RDN. Mortality and HF-related hospitalization rates were relatively low. There was no significant change in eGFR or creatinine after RDN. CONCLUSIONS: Our findings suggest that RDN can effectively increase LVEF and 6MWD in patients with HFrEF but require confirmation in studies with larger sample sizes and longer follow-up durations.

Comparative effectiveness and safety of bolus vs. continuous infusion of loop diuretics: Results from the MIMIC-III Database.

BACKGROUND: It is unclear whether fluid management goals are best achieved by bolus injection or continuous infusion of loop diuretics. In this study, we compared the effectiveness and safety of a continuous infusion with that of a bolus injection when an increased loop diuretic dosage is required in intensive care unit (ICU) patients. METHODS: We obtained data from the MIMIC-III database for patients who were first-time ICU admissions and required an increased diuretic dosage. Patients were excluded if they had an estimated glomerular filtration rate <15 ml/min/1.73 m2, were receiving renal replacement therapy, had a baseline systolic blood pressure <80 mmHg, or required a furosemide dose <120 mg. The patients were divided into a continuous group and a bolus group. Propensity score matching was used to balance patients' background characteristics. RESULTS: The final dataset included 807 patients (continuous group, n = 409; bolus group, n = 398). After propensity score matching, there were 253 patients in the bolus group and 231 in the continuous group. The 24 h urine output per 40 mg of furosemide was significantly greater in the continuous group than in the bolus group (234.66 ml [95% confidence interval (CI) 152.13-317.18, p < 0.01]). There was no significant between-group difference in the incidence of acute kidney injury (odds ratio 0.96, 95% CI 0.66-1.41, p = 0.85). CONCLUSIONS: Our results indicate that a continuous infusion of loop diuretics may be more effective than a bolus injection and does not increase the risk of acute kidney injury in patients who need an increased diuretic dosage in the ICU.

PCSK9 inhibitors in a renal transplant patient complicated with hepatitis B: A case report and literature review.

Lipid metabolism disorders are recognized to be one of the most frequent complications of renal transplantation, while dyslipidemia and chronic kidney disease (CKD) are strong risk factors for arteriosclerotic cardiovascular disease (ASCVD). Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are novel lipid-lowering drugs, the safety and efficacy of which are yet to be confirmed in transplanted patients. There have been several small-sample studies using PCSK9i in patients after heart transplantation, while fewer cases use PCSK9i after kidney transplantation. We report a case of a renal transplant recipient complicated with hepatitis B treated with PCSK9i, which achieved a remarkable lipid-lowering efficacy, and no significant adverse effects were found during the follow-up.

Association between plasma vitamin B5 and coronary heart disease: Results from a case-control study.

Aim: The relationship of vitamin B5 and coronary heart disease (CHD) is still uncertain. This case-control study was performed to evaluate the relationship between the plasma vitamin B5 concentration and the risk of CHD. Materials and methods: The study involved 429 patients with >70% stenosis of the coronary arteries on coronary angiography and 429 matched controls were included for age ± 2 years, gender, and date of coronary angiography examination ± 180 days. Logistic regression analyses were performed to evaluate the association between plasma vitamin B5 and the risk of CHD. Results: An L-shaped relationship was found between the plasma vitamin B5 concentration and CHD. Compared with patients with low vitamin B5 (first quartile, <27.6 ng/ml), the odds ratio (OR) and 95% confidence interval (CI) for participants in the third quartile (34.9-44.0 ng/ml) and fourth quartile (≥44.0 ng/ml) were 0.42 (95% CI, 0.26-0.70) and 0.49 (95% CI, 0.29-0.82), respectively. In the threshold effect analysis, the risk of CHD significantly decreased as the vitamin B5 concentration increased (per 10 ng/ml increment: OR, 0.71; 95% CI, 0.57-0.89) in participants with a plasma vitamin B5 concentration of <40.95 ng/ml; however, an increased plasma vitamin B5 concentration was no longer associated with a decreased risk of CHD (per 10 ng/ml increment: OR, 1.00; 95% CI, 0.87-1.14) in participants with a plasma vitamin B5 concentration of ≥40.95 ng/ml. The association between vitamin B5 and CHD was stronger in ever or current smokers than non-smokers (p-interaction = 0.046). Conclusion: Plasma vitamin B5 has an L-shaped relationship with CHD, with a threshold around 40.95 ng/ml. This association was modified by smoking.

Effect of sodium-glucose cotransporter-2 inhibitors on blood pressure in patients with heart failure: a systematic review and meta-analysis.

BACKGROUND: Recent studies have shown that sodium-glucose cotransporter-2 inhibitors (SGLT2i) can achieve significant improvement in blood pressure in people with diabetes. Furthermore, randomized controlled trials (RCTs) have established that SGLT2i have a cardioprotective effect in adults with heart failure (HF). Therefore, we performed this systematic review an meta-analysis to determine the effect of SGLT2i on blood pressure in patients with HF. METHODS: We used the Medline, Cochrane Library, Embase, and PubMed databases to identify RCTs (published through to April 29, 2022) that evaluated the effect of SGLT2i on HF. The primary endpoint was defined as change in blood pressure. Secondary composite outcomes were heart rate, hematocrit, body weight, and glycated hemoglobin. The N-terminal pro-brain natriuretic peptide level, Kansas City Cardiomyopathy Questionnaire scores, and estimated glomerular filtration rate were also evaluated. RESULTS: After a literature search and detailed evaluation, 16 RCTs were included in the quantitative analysis. Pooled analyses showed that SGLT2i were associated with a statistically significant reduction in systolic blood pressure of 1.68 mmHg (95% confidence interval [CI] - 2.7, - 0.66; P = 0.001; I2 = 45%) but not diastolic blood pressure (mean difference [MD] -1.06 mmHg; 95% CI -3.20, 1.08; P = 0.33; I2 = 43%) in comparison with controls. Furthermore, SGLT2i decreased body weight (MD - 1.36 kg, 95% CI - 1.68, - 1.03; P < 0.001; I2 = 61%) and the glycated hemoglobin level (MD - 0.16%, 95% CI - 0.28, -0.04, P = 0.007; I2 = 91%) but increased hematocrit (MD 1.63%, 95% CI 0.63, 2.62, P = 0.001; I2 = 100%). There was no significant between-group difference in heart rate (MD - 0.35; 95% CI - 2.05, 1.35, P = 0.69; I2 = 0). CONCLUSIONS: SGLT2i decreased systolic blood pressure in patients with HF but had no effect on diastolic blood pressure. These inhibitors may have numerous potentially beneficial clinical effects in patients with HF.

Haemodynamic changes of interatrial shunting devices for heart failure: a systematic review and meta-analysis.

AIMS: To assess the efficacy and safety, primarily in relation to the haemodynamic effects, of interatrial shunting devices (ISD) for the treatment of heart failure (HF), we conducted a systematic review and a meta-analysis. METHODS AND RESULTS: We used the MEDLINE, Cochrane Library, Embase, and PubMed databases to identify clinical studies (published to 4 August 2021) that evaluated the effect of ISD on HF. The primary endpoint was defined as changes in pulmonary capillary wedge pressure (PCWP). Secondary endpoints included (i) other haemodynamic indexes, including cardiac output (CO), right atrial pressure (RAP), and mean pulmonary artery pressure (mPAP) by right heart catheterization, and (ii) change from baseline in 6 min walk distance (6MWD). After a literature search and detailed evaluation, six trials enrolling a total of 203 individuals were included in the quantitative analysis. Pooled analyses showed that after ISD implantation, PCWP decreased by a mean 3.10 mmHg [95% confidence interval (CI) -4.56 to -1.64; I2  = 0%; P < 0.0001]. Overall, CO increased by 0.77 L/min (95% CI 0.02 to 1.52; P = 0.04; I2  = 82%), but there were no significant changes in RAP or mPAP. The mean 6MWD increased by 32.33 m (95% CI 10.74 to 53.92; P = 0.003; I2  = 0) after ISD implantation. CONCLUSIONS: Interatrial shunting device can effectively reduce PCWP, increase CO and 6MWD, and has no obvious adverse effects on the right heart and pulmonary pressure. Studies with larger sample size and longer follow-up time are needed for further verification.

Joint Predictive Value of cTnI and NT-proBNP on Mortality in Patients with Coronavirus Disease 2019: A Retrospective Research in Wuhan, China.

BACKGROUND AND OBJECTIVES: The pandemic of coronavirus disease 2019 (COVID-19) remains to be the biggest public threat all over the world. Because of the rapid deterioration in some patients, markers that could predict poor clinical outcomes are urgently required. This study was to evaluate the predictive values of cardiac injury parameters, including cardiac troponin I (cTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, on mortality in COVID-19 patients. METHODS: COVID-19 patients in Zhongfaxincheng branch of Tongji Hospital (Wuhan, China) from February 8-28, 2020, were enrolled in this study. We followed up the patients for 30 days after admission. RESULTS: A total of 134 patients were included in the study. Multivariate Cox regression showed that 1) patients with elevated cTnI levels had a higher risk of death (hazard ratio [HR] 7.33, 95% confidence interval [CI] 2.56-21.00) than patients with normal cTnI levels; 2) patients with elevated NT-proBNP levels had a higher risk of death (HR 27.88, 95% CI 3.55-218.78) than patients with normal NT-proBNP levels; 3) patients with both elevated cTnI and NT-proBNP levels had a significantly higher risk of death (HR 53.87, 95% CI 6.31-459.91, P < 0.001) compared to patients without elevated cTnI or NT-proBNP levels; 4) the progressions of cTnI and NT-proBNP levels were also correlated with death (HR 12.70, 95% CI 3.94-40.88, P < 0.001 and HR 51.09, 95% CI 5.82-448.26, P < 0.001). CONCLUSIONS: In COVID-19 patients, cTnI and NT-proBNP levels could be monitored to identify patients at a high risk of death in their later course of disease.

Association Between Average Plasma Potassium Levels and 30-day Mortality During Hospitalization in Patients with COVID-19 in Wuhan, China.

Background: Coronavirus disease 2019 (COVID-19) has resulted in more than 610,000 deaths worldwide since December 2019. Given the rapid deterioration of patients' condition before death, markers with efficient prognostic values are urgently required. During the treatment process, notable changes in plasma potassium levels have been observed among severely ill patients. We aimed to evaluate the association between average plasma potassium (Ka +) levels during hospitalization and 30-day mortality in patients with COVID-19. Methods: Consecutive patients with COVID-19 hospitalized in the Zhongfaxincheng branch of Tongji Hospital in Wuhan, China from February 8 to 28, 2020 were enrolled in this study. We followed patients up to 30 days after admission. Results: A total of 136 patients were included in the study. The average age was 62.1±14.6 years and 51.5% of patients were male. The median baseline potassium level was 4.3 (3.9-4.6) mmol/L and Ka + level during hospitalization was 4.4 (4.2-4.7) mmol/L; the median number of times that we measured potassium was 4 (3-5). The 30-day mortality was 19.1%. A J-shaped association was observed between Ka + and 30-day mortality. Multivariate Cox regression showed that compared with the reference group (Ka + 4.0 to <4.5 mmol/L), 30-day mortality was 1.99 (95% confidence interval [CI]=0.54-7.35, P=0.300), 1.14 (95% CI=0.39-3.32, P=0.810), and 4.14 (95% CI=1.29-13.29, P=0.017) times higher in patients with COVID-19 who had Ka + <4.0, 4.5 to <5.0, and ≥5.0 mmol/L, respectively. Conclusion: Patients with COVID-19 who had a Ka + level ≥5.0 mmol/L had a significantly increased 30-day mortality compared with those who had a Ka + level 4.0 to <4.5 mmol/L. Plasma potassium levels should be monitored routinely and maintained within appropriate ranges in patients with COVID-19.

Elevated resting heart rates are a risk factor for mortality among patients with coronavirus disease 2019 in Wuhan, China.

BACKGROUND: We evaluated the association between higher resting heart rates (RHRs) and adverse events in COVID-19 patients. METHODS: One hundred and thirty-six patients with laboratory-confirmed COVID-19 were admitted. Outcomes of patients with different RHRs were compared. RESULTS: Twenty-nine patients had RHRs of <80 bpm (beat per min), 85 had 80-99 bpm and 22 had ≥100 bpm as tachycardia. Those with higher RHRs had lower pulse oxygen saturation (SpO2) and higher temperatures, and there was a higher proportion of men upon admission (all P < 0.05). Patients with higher RHRs showed higher white blood cell counts and D-dimer, cardiac troponin I (TnI), N-terminal pro-B-type natriuretic peptide and hypersensitive C-reactive protein levels, but lower albumin levels (all P < 0.05) after admission. During follow-up, 26 patients died (mortality rate, 19.1%). The mortality rate was significantly higher among patients with tachycardia than among the moderate and low RHR groups (all P < 0.001). Kaplan-Meier survival curves showed that the risks of death and ventilation use increased for patients with tachycardia (P < 0.001). Elevated RHR as a continuous variable and a mean RHR as tachycardia were independent risk factors for mortality and ventilator use (all P < 0.05) in the multivariable adjusted Cox proportional hazards regression model. CONCLUSIONS: Elevated average RHRs during the first 3 days of hospitalisation were associated with adverse outcomes in COVID-19 patients. Average RHRs as tachycardia can independently predict all-cause mortality.

Association of Plasma Vitamin B6 With Coronary Heart Disease in Patients Undergoing Diagnostic Coronary Angiography: New Insight on Sex Differences.

Aim: To date, findings on the overall and sex-specific effects of plasma pyridoxal 5'-phosphate (PLP, active coenzyme form of vitamin B6) on the risk of coronary heart disease (CHD) have been inconsistent. This study sought to advance our understanding on the association of plasma PLP with risk of CHD, with particular attention paid to sex differences and effect modifiers. Methods: We conducted a hospital-based, case-control study on suspected CHD patients undergoing diagnostic coronary angiography. A total of 429 CHD cases and 429 controls matched by age, sex, and operation time were included in the final analysis. Plasma PLP was assessed using LC-MS. Logistic regression analyses were performed to evaluate the association between plasma PLP and a first CHD event. Results: The mean (SD) plasma PLP levels were 8.4 (6.3) in male cases and 9.0 (11.0) in female cases, and 9.5 (8.5) in male controls and 12.5 (12.9) in female controls. Each 1 ng/mL increment in log2PLP was associated with a 28% lower risk of CHD in overall population. When stratified by sex, plasma PLP was significantly and independently associated with CHD in women (OR = 0.63, 95% CI: 0.50-0.80), but not in men (OR = 0.86, 95% CI: 0.67-1.09). The association of plasma PLP with CHD risk was modified by sex (adjusted P interaction = 0.022). Conclusions: We found a significant, inverse linear association between plasma PLP and CHD in Chinese women, but not in men. Our findings warrant additional investigation.

Association of brachial-ankle pulse wave velocity and carotid plaque in Chinese hypertensive adults: effect modification by age.

We aimed to investigate the association of brachial-ankle pulse wave velocity (baPWV) with carotid plaque presence and carotid plaque number in a Chinese hypertensive population. A total of 13,554 hypertensive subjects from the China Stroke Primary Prevention Trial (CSPPT) were recruited. Arterial stiffness and carotid plaque were evaluated by baPWV and B-mode ultrasonography, respectively. Multivariate logistic regression analysis was used to determine the correlation of baPWV and carotid plaque presence. Multinomial logistic regression analysis was used to determine the correlation of baPWV and carotid plaque number. Further interactions between baPWV and carotid plaque presence were examined using subgroup analysis. Continuous baPWV was positively correlated with carotid plaque presence (OR = 1.05, 95% CI: 1.04-1.07) and carotid plaque number (one- to two-plaque group: OR = 1.04, 95% CI: 1.02-1.06; three-or-more-plaque group: OR = 1.09, 95% CI: 1.07-1.12). When baPWV was classified into quartiles, with the lowest quartile as reference, the ORs for having one, two, or three or more plaques increased in parallel with the quartiles of baPWV, indicating a dose-dependent effect. In a subgroup analysis, the association of baPWV and carotid plaque presence was more pronounced among younger participants (OR: 1.14 vs. 1.06 and 1.03 for the age groups <60 years, 60 ≤ 70 years, and ≥70 years, respectively, P for interaction <0.001). In a Chinese hypertensive population, baPWV was positively associated with carotid plaque presence and carotid plaque number. A more pronounced positive association between baPWV and carotid plaque presence was observed in younger participants.

The association between total homocysteine and blood pressure in two independent Chinese populations.

Hypertension and hyperhomocystinemia have a joint effect on the risk of stroke. We aimed to evaluate the relationship between plasma total homocysteine (tHcy) and blood pressure in two independent Chinese populations. Four thousand five hundred and fifty-five participants who underwent health examinations between March 2016 and September 2016 at Peking University First Hospital were enrolled as 'Population 1', and 2689 participants who were admitted to Peking University First Hospital between January 2014 and December 2015 were enrolled as 'Population 2'. None of the study participants were taking antihypertensive medication or vitamins, or had cardio-cerebrovascular disease or chronic kidney disease stages 4 or 5. In Population 1, a 5 µmol/L increase in tHcy was associated with a 0.47 mmHg (95% confidence interval [CI]: 0.23-0.70 mmHg, p < 0.01) increase in systolic blood pressure (SBP) and a 0.14 mmHg (95% CI: -0.02 to 0.30 mmHg, p = 0.08) increase in diastolic blood pressure (DBP). In Population 2, a 5 µmol/L increase in tHcy was associated with a 0.42 mmHg (95% CI: 0.13-0.72 mmHg, p < 0.01) increase in SBP and a 0.29 mmHg (95% CI: 0.09-0.49 mmHg, p < 0.01) increase in DBP. The prevalence of hypertension was significantly higher in Population 1 (by 47%; odds ratio [OR] 1.47, 95% CI: 1.09-1.98, p = 0.01) and in Population 2 (by 55%;OR 1.55, 95% CI: 1.15-2.08, p < 0.01) in participants with tHcy ≥ 15 µmol/l than in those with tHcy < 10 µmol/L. Stratified analysis showed that the association was stronger in women than in men.

Lorf9 deletion significantly eliminated lymphoid organ atrophy induced by meq-deleted very virulent Marek's disease virus.

Marek's disease virus (MDV) is a highly contagious alphaherpesvirus that causes rapid onset of T cell lymphomas in chickens. MDV continues to break through vaccinal immunity due to the emergence of highly virulent field strains. Earlier studies revealed that deletion of the meq gene from MDV results in attenuated vaccines that protect against disease when chickens are infected with highly virulent strains. However, meq-deleted viruses still retain the ability to induce lymphoid organ atrophy, which raises safety concerns. In an earlier study, we found that deletion of lorf9 counteracts this lymphoid organ atrophy. Here, we describe the generation of a double deletion mutant virus lacking virus-encoded meq and lorf9. In vitro studies revealed that during replication, the mutant virus had kinetic characteristics similar to the parental virus; however, in vivo the replication capability was significantly reduced. Results of animal studies revealed no obvious MDV-specific symptoms and lesions. Importantly, the double deletion mutant virus lost the capacity to induce lymphoid organ atrophy, which has been the main obstacle during development of a good vaccine candidate.

Farnesoid X receptor (FXR) gene deficiency impairs urine concentration in mice.

The farnesoid X receptor (FXR) is a ligand-activated transcription factor belonging to the nuclear receptor superfamily. FXR is mainly expressed in liver and small intestine, where it plays an important role in bile acid, lipid, and glucose metabolism. The kidney also has a high FXR expression level, with its physiological function unknown. Here we demonstrate that FXR is ubiquitously distributed in renal tubules. FXR agonist treatment significantly lowered urine volume and increased urine osmolality, whereas FXR knockout mice exhibited an impaired urine concentrating ability, which led to a polyuria phenotype. We further found that treatment of C57BL/6 mice with chenodeoxycholic acid, an FXR endogenous ligand, significantly up-regulated renal aquaporin 2 (AQP2) expression, whereas FXR gene deficiency markedly reduced AQP2 expression levels in the kidney. In vitro studies showed that the AQP2 gene promoter contained a putative FXR response element site, which can be bound and activated by FXR, resulting in a significant increase of AQP2 transcription in cultured primary inner medullary collecting duct cells. In conclusion, the present study demonstrates that FXR plays a critical role in the regulation of urine volume, and its activation increases urinary concentrating capacity mainly via up-regulating its target gene AQP2 expression in the collecting ducts.