Analysis of Obstructive Sleep Apnoea in Craniofacial Microsomia Based on Polysomnography.

OBJECTIVE: This study aimed to investigate the prevalence of obstructive sleep apnoea (OSA) in patients with craniofacial microsomia (CFM) through polysomnography (PSG) and the relationship with the severity of CFM. METHODS: This study reviewed patients of CFM with pre-operative PSG data between January 2005 and September 2023. Patients were grouped according to the Pruzansky-Kaban classification. OSA was diagnosed and severity was assessed by the obstructive apnea-hypopnea index. The Pediatric Sleep Questionnaire was used to investigate OSA-related signs and symptoms. The χ 2 test and Fisher's exact test were used to compare between groups. Univariate logistic regression was used to identify risk factors associated with OSA. A p-value less than 0.05 was considered statistically significant. RESULTS: A total of 121 patients with CFM were included in the study with 3 bilateral and 118 unilateral patients. In total, 86 patients (71.07%) were diagnosed with OSA. The prevalence of OSA in type IIa, type IIb and type III was 72.97%, 78.33%, and 47.62%. There was no statistically significant difference in the prevalence of OSA between type IIa and type IIb (p > .05). The difference in the prevalence of OSA between type III and type II was statistically significant (p < .05). Snoring was the most common symptom among the patients of CFM with OSA. CONCLUSIONS: Patients with CFM have a higher incidence of OSA based on PSG in type II and type III patients. The incidence of OSA did not correlate positively with the severity of CFM, with type III patients having certain particularities.

A Novel Method for one-Stage Repair of the lip Vermilion Defects in Progressive Hemifacial Atrophy.

BACKGROUND: Progressive hemifacial atrophy often causes lip vermilion defects in patients. In this study, we described a one-stage repair method for lip defects in progressive hemifacial atrophy using a lip vermilion mucosal flap or combined dermal fat flap graft. PATIENTS AND METHODS: Patients diagnosed with progressive hemifacial atrophy with lip vermilion defects from 2010 to 2022 were included in this study. Based on the severity and location of the patient's lip defect, a lip vermilion mucosal flap was designed and transferred to the lip defect or combined with a hip dermal fat flap for one-stage repair of the lip morphology. Lip morphology and function of patients were followed up after surgery. RESULTS: A total of 22 patients were enrolled in this study, including 15 patients with lip defects on the upper lip alone and 7 patients with both upper and lower lip defects. Follow-up six months to two years postoperatively, all patients recovered uneventfully without complications. The repaired lips of the patient had a full and symmetrical morphology with no visible scarring. Two patients experienced transient dysesthesia of the lips postoperatively and both returned to normal after three months. All patients had good lip closure with normal dietary and speech function. CONCLUSIONS: The method we described for repairing lip defects in progressive hemifacial atrophy can achieve satisfactory aesthetic and functional lip results. The distinct advantage of this approach is that the patients undergo only one-stage operation and it can be used to repair both upper and lower lip defects.

Possible sarcopenia and risk of new-onset type 2 diabetes mellitus in older adults in China: a 7-year longitudinal cohort study.

BACKGROUND: Previous studies have shown that type 2 diabetes mellitus (T2DM) can cause sarcopenia; however, these conditions may have a bidirectional association. This study aimed to explore the longitudinal association between possible sarcopenia and new-onset T2DM. METHODS: We conducted a population-based cohort study using nationally representative data from the China Health and Retirement Longitudinal Study (CHARLS). This study included participants aged ≥ 60 years who were free of diabetes during the baseline survey of CHARLS (2011 to 2012) and were followed up until 2018. Possible sarcopenia status was defined according to the Asian Working Group for Sarcopenia 2019 criteria. Cox proportional hazards regression models were used to evaluate the effect of possible sarcopenia on new-onset T2DM. RESULTS: In total, 3,707 individuals were enrolled in this study, with a median age of 66 years; the prevalence of possible sarcopenia was 45.1%. During the 7-year follow-up, 575 cases (15.5%) of incident diabetes were identified. Participants with possible sarcopenia were more likely to have new-onset T2DM than those without possible sarcopenia (hazard ratio: 1.27, 95% confidence interval: 1.07-1.50; p = 0.006). In subgroup analysis, we found a significant association between possible sarcopenia and T2DM in individuals aged < 75 years or with a BMI < 24 kg/m². However, this association was not significant in individuals aged ≥ 75 years or with a BMI ≥ 24 kg/m². CONCLUSIONS: Possible sarcopenia is associated with an increased risk of new-onset T2DM in older adults, especially in individuals who are not overweight and aged 75 years or younger.

Respiratory outcome of mandibular distraction osteogenesis on obstructive sleep apnea in craniofacial microsomia: A retrospective study.

This study aimed to evaluate the effect of mandibular distraction osteogenesis (MDO) on respiratory function in CFM patients with obstructive sleep apnea (OSA) according to polysomnography (PSG). This study retrospectively analyzed patients with CFM who underwent PSG before surgery and after completion of mandible distraction. Patients who met the inclusion criteria were selected. The Pediatric Sleep Questionnaire (PSQ) was used to assess patients' signs and symptoms related to OSA. The obstructive apnea-hypopnea index (OAHI) and lowest oxygen saturation (LSaO2) were imported into SPSS version 26.0. The Wilcoxon signed-rank test was used to assess the differences in PSG before and after MDO. Other data were described using descriptive statistics. A P-value less than 0.05 was considered statistically significant. A total of 25 unilateral CFM patients were included in this study. Most patients (72%) had mild OSA; moderate and severe OSA were 12% and 16%, respectively. Snoring (52%) was the most common symptom among these patients. After completion of mandibular distraction, snoring and other OSA-related symptoms were significantly improved. Twelve patients had normalized PSG and the severity of OSA improved significantly in 3 patients. The total effective rate of MDO for OSA was 60%. The statistical results showed that OAHI (P = 0.045) decreased and LSaO2 (P = 0.009) increased significantly compared to preoperative values. MDO can improve OSA-related symptoms in CFM patients. In addition, respiratory function was improved in most patients after MDO, based on PSG. CFM patients, especially those with OSA, can benefit from MDO.

Neuronal nitric oxide synthase/reactive oxygen species pathway is involved in apoptosis and pyroptosis in epilepsy.

Dysfunction of neuronal nitric oxide synthase contributes to neurotoxicity, which triggers cell death in various neuropathological diseases, including epilepsy. Studies have shown that inhibition of neuronal nitric oxide synthase activity increases the epilepsy threshold, that is, has an anticonvulsant effect. However, the exact role and potential mechanism of neuronal nitric oxide synthase in seizures are still unclear. In this study, we performed RNA sequencing, functional enrichment analysis, and weighted gene coexpression network analysis of the hippocampus of tremor rats, a rat model of genetic epilepsy. We found damaged hippocampal mitochondria and abnormal succinate dehydrogenase level and Na+-K+-ATPase activity. In addition, we used a pilocarpine-induced N2a cell model to mimic epileptic injury. After application of neuronal nitric oxide synthase inhibitor 7-nitroindazole, changes in malondialdehyde, lactate dehydrogenase and superoxide dismutase, which are associated with oxidative stress, were reversed, and the increase in reactive oxygen species level was reversed by 7-nitroindazole or reactive oxygen species inhibitor N-acetylcysteine. Application of 7-nitroindazole or N-acetylcysteine downregulated the expression of caspase-3 and cytochrome c and reversed the apoptosis of epileptic cells. Furthermore, 7-nitroindazole or N-acetylcysteine downregulated the abnormally high expression of NLRP3, gasdermin-D, interleukin-1ß and interleukin-18. This indicated that 7-nitroindazole and N-acetylcysteine each reversed epileptic cell death. Taken together, our findings suggest that the neuronal nitric oxide synthase/reactive oxygen species pathway is involved in pyroptosis of epileptic cells, and inhibiting neuronal nitric oxide synthase activity or its induced oxidative stress may play a neuroprotective role in epilepsy.

Mandibular Distraction Osteogenesis First for Children With Severe Unilateral Hemifacial Microsomia: Treatment Strategy and Outcomes.

ABSTRACT: The treatment for severe hemifacial microsomia (HFM), especially type III case, is extremely difficult. Mandibular distraction osteogenesis (MDO) was rarely used as the primary choice in the treatment of severe type cases. The authors sought to observe the short-term therapeutic outcomes of patients with severe unilateral HFM who underwent MDO first.A retrospective study of children underwent MDO or later received costochondral graft (CCG) for severe unilateral HFM from 2009 to 2019 was conducted. Cephalometric measurements and clinical variables were analyzed to evaluate the effectiveness of MDO first strategy for severe cases and compare disparity between Pruzansky-Kaban classification type IIb and type III groups.Thirty-six patients (23 males and 13 females) underwent MDO first for severe HFM were included for analysis in the present study. The average age at MDO was 8.33 ±â€Š2.03 years. At the last follow-up, MDO acquired significant improvement in mandibular height, maxillary cant, chin deviation, lip commissural line tilt, and clinical chin deviation (P < 0.05). Distraction results were stable during the short-term follow-up in terms of the mandibular height ratio and maxillary cant (P > 0.05).MDO is a proper primary method for suitable type IIb and type III HFM cases. MDO can immediately and significantly improve the facial skeleton deficiency, extend the associated soft tissue at the same time, and lay foundation for secondary surgery. MDO can achieve the downgrade of HFM deficiency severity. MDO followed by costochondral graft can get satisfactory esthetic and structural consequence for type III patients.

The spectrum and prevalence of arrhythmia in different clinical pulmonary hypertension groups in Chinese population.

BACKGROUND: Arrhythmia is not uncommon among pulmonary hypertension (PH) population, and may be associated with disease severity. HYPOTHESIS: To investigate different spectrums and prevalence of arrhythmias in different clinical PH groups in Chinese population. METHODS: Patients diagnosed with PH between April 15, 2019, and August 2, 2021, were enrolled prospectively. The prevalence of different types of arrhythmias in PH patients were calculated. Logistic regression analyses were conducted to determine independent predictors for arrhythmia. RESULTS: One thousand patients were enrolled. The prevalence of any arrhythmia, sinus node dysfunction, sinus tachycardia, atrial fibrillation, atrial flutter, other types of atrial tachycardia, atrioventricular block, and ventricular tachycardia is 44.4%, 12.2%, 15.2%, 8.1%, 4.1%, 10.2%, 7.1%, and 2.5%. Logistic regression analyses revealed that older age and larger right ventricle (odds ratio: 1.111 and 1.095, p < .05) were independently related with higher probability of supraventricular arrhythmia; Complicating with coronary artery disease, larger right ventricle, and increased left ventricular end-diastolic diameter (odds ratio: 19.540, 1.106, and 1.085, p < .05) were independently correlated with sinus node dysfunction/atrioventricular block in patients with pulmonary arterial hypertension. CONCLUSIONS: Nearly half of PH patients experienced at least one type of arrhythmia. The most common seen arrhythmias were supraventricular arrhythmia, sinus tachycardia, and sinus node dysfunction. Older age and larger right ventricle were independently related with higher probability of supraventricular arrhythmia; Complicating with coronary artery disease, larger right ventricle and increased left ventricular end-diastolic diameter were independently correlated with higher probability of sinus node dysfunction/atrioventricular block in patients with pulmonary arterial hypertension.

Responses of greenhouse gas emissions to residue returning in China's croplands and influential factors: A meta-analysis.

Climate change is a global issue threatening agricultural production and human survival. However, agriculture sector is a major source of global greenhouse gases (GHGs), especially CH4 and N2O. Crop residue returning (RR) is an efficient practice to sequestrate soil carbon and increase crop yields. However, the efficiency of RR to mitigate climate change and maintain food security will be affected by the response of GHG emissions at both per area-scale and per yield-scale. Therefore, a national meta-analysis was conducted using 309 comparisons from 44 publications to assess the responses of GHG emissions to RR in China's croplands. The results indicated that little response of GWP to RR was observed with conditions under lower nitrogen fertilizer input rates (0-120 kg ha-1), mulch retention, returning one time in double cropping systems, returning with half residue, weakly acidic soil (pH 5.5-6.5), initial SOC contents >20 g kg-1, or mean annual precipitation <1000 mm. In order to mitigate climate change and sustain food security, RR combined with paddy-upland rotation, nitrogen fertilizer input rates of 240-360 kg ha-1, and neutral soil (pH 6.5-7.5) could decrease GWP at per unit of crop yield, which ultimately leads to a lower effect on GHGI and a higher crop production efficiency. In-depth studies should be conducted in the future to explore the interactions between various factors influencing GHG emissions under RR conditions. Overall, optimizing the interactions with management and site-specific conditions, potential for regulating GHGs emissions of RR can be enhanced.

mTOR-autophagy promotes pulmonary senescence through IMP1 in chronic toxicity of methamphetamine.

It is growingly concerned about methamphetamine (MA)-induced lung toxicity. IMP1 is identified as a key molecule for cell life processes, but the role of IMP1 in MA-induced senescence remains unclear. The purpose of this study was to investigate whether chronic exposure to MA can cause autophagy and senescence of the lungs, whether there are interactions between Mammalian target of rapamycin (mTOR) and IMP1 and whether IMP1 is involved in pulmonary senescence promoted by mTOR-autophagy. The rats were randomly divided into control group and MA group, following by H&E staining, immunohistochemistry staining and Western blot. The alveolar epithelial cells were proceeded by ß-galactosidase staining, cell cycle detection, transfection and co-immunoprecipitation. Long-term exposure to MA led to the thickening of alveolar septum and more compact lungs. MA promoted the conversion of LC3-I to LC3-II and inhibited the activation of mTOR to induce autophagy. Bioinformatics and co-immunoprecipitation results presented the interactions between IMP1 and mTOR. MA induced cell senescence by decreasing IMP1, up-regulating p21 and p53, arresting cell cycle and increasing SA-ß-gal. Overexpression of IMP1 reduced p21 and SA-ß-gal to inhibit the senescence of alveolar epithelial cells. These results demonstrated that mTOR-autophagy promotes pulmonary senescence through IMP1 in chronic toxicity of methamphetamine.

RUNX3-dependent oxidative epithelial-to-mesenchymal transition in methamphetamine-induced chronic lung injury.

Lung toxicity is the main cause of the death from methamphetamine (MA) abuse, but its mechanism has remained unclear. The purpose of our study was to investigate if MA can induce epithelial-to-mesenchymal transition (EMT) and if RUNX3 is involved in oxidative EMT in MA-induced chronic lung injury. The rats were divided into the control group and MA group. Extracted lungs were used for morphological measurements and Western blot. The alveolar epithelial cells were cultured or transfected and then treated with MA or/and N-acetyl cysteine (NAC) followed by flow cytometry, Western blot, and immunohistochemistry. Chronic exposure to MA resulted in the lower growth ratio of weight, increased right ventricular index, thickened alveolar walls, and reduced number of alveolar sacs. Long-term administration with MA caused oxidative stress and pulmonary EMT. NAC increased RUNX3 and alleviated EMT. However, after knockdown of RUNX3, reactive oxygen species (ROS) levels were significantly upregulated, indicating that RUNX3 was closely related to oxidative stress. Knockdown of RUNX3 aggravated MA-induced EMT by activating RUNX3-dependent TGF-ß signaling. Therefore, RUNX3 may be the key to oxidative EMT in methamphetamine-induced chronic lung injury.

Two-dimensional speckle tracking echocardiography detected interventricular dyssynchrony predicts exercise capacity and disease severity in pre-capillary pulmonary hypertension.

BACKGROUND: Right ventricular (RV) intraventricular mechanical dyssynchrony detected by two-dimensional speckle tracking echocardiography (2D-STE) has been reported to be correlated with a decrease in RV contractile efficiency in pulmonary hypertension (PH) patients, while little attention has been paid to biventricular dysfunction. Therefore, we aimed to evaluate the predictive value of 2D-STE detected interventricular dyssynchrony for exercise capacity and disease severity in patients with pre-capillary PH (PcPH). METHODS: Conventional transthoracic echocardiography, 2D-STE and cardiopulmonary exercise tests (CPETs) were performed in all participants. Intra- and interventricular dyssynchrony were calculated as the standard deviation (SD) of the time intervals corrected for heart rate between QRS onset and peak longitudinal strain. Multivariate linear regression analyses were performed to identify independent predictors of peak oxygen consumption (PVO2) during the CPET. Multivariable logistical regression modeling was used to analyze the associations between interventricular dyssynchrony and risk assessment. RESULTS: Sixty-six PcPH patients were consecutively recruited (19 male and 47 female, average 35 years old). WHO functional class, N-terminal pro-brain natriuretic peptide (BNP) and body mass index were included as independent predictors in the first multivariate regression analysis of clinical data without echocardiographic parameters (Model-1, r2=0.423, P<0.001). We subsequently added conventional echocardiographic parameters and 2D-STE parameters to the clinical data, RV fractional area change (Model-2, r2=0.417, P<0.001), RV global longitudinal strain (Model-3, r2=0.454, P=0.001), RV intraventricular dyssynchrony (Model-4: r2=0.474, P<0.001) and interventricular dyssynchrony (Model-5, r2=0.483, P<0.001) were identified as independent predictors of PVO2. Interventricular dyssynchrony, calculated as the SD of the time intervals of nine segments, was independently associated with risk assessment (odd ratio 1.027, 95% CI: 1.003-1.052, P=0.03). The area under the receiver-operating characteristic curve (AUC) was 0.73 (P<0.001). CONCLUSIONS: Interventricular dyssynchrony detected by 2D-STE contributed to a better evaluation of exercise capacity and disease severity in PcPH patients.

The circulating level of miR-122 is a potential risk factor for endothelial dysfunction in young patients with essential hypertension.

MicroRNAs are key molecules involved in the regulation of endothelial function. They are important risk factors and biomarkers for the development of hypertension related to endothelial dysfunction. However, the gene expression patterns associated with hypertension development related to endothelial dysfunction have not been fully elucidated. We conducted a case-control study of 65 patients with essential hypertension (EH) and 61 controls without EH. Plasma levels of miR-122 and its target protein high-affinity cationic amino acid transporter 1 (CAT-1) were measured by qRT-PCR and ELISA, respectively. miR-122 expression in plasma of patients with EH was significantly higher than that of the control group (p = 0.001), while CAT-1 expression in patients with EH was significantly lower than that in the control group (p = 0.018). miR-122 expression in plasma of young patients with EH was significantly higher than that in young people without EH (p = 0.0004), and CAT-1 expression in plasma of young patients with EH was also significantly lower than that of the control group (p = 0.002). CAT-1 expression in the plasma of young participants was significantly higher than that of individuals aged ≥40 years (p = 0.003), whereas miR-122 expression was significantly lower (p = 0.001). We showed that among patients with EH, the high expression of miR-122 contributed to endothelial dysfunction by suppressing the expression of the CAT-1 protein, which led to a decrease in CAT-1 expression in plasma. Therefore, high expression of miR-122 appears to be a risk factor for endothelial dysfunction in EH, especially in younger patients.

The value of three-dimensional echocardiography in risk stratification in pulmonary arterial hypertension: a cross-sectional study.

To explore the value of right ventricular (RV) parameters detected by three-dimensional echocardiography (3DE) in risk stratification in pulmonary arterial hypertension (PAH) patients. We prospectively recruited 130 pulmonary hypertension patients from National Center for Cardiovascular Diseases, Fuwai Hospital. Each participant was performed a transthoracic echocardiography and 3DE parameters were measured using an off-line software (4D RV Function 2.0, TomTec). Patients were classified into low, intermediate-high risk group based on 2015 ESC Guidelines. A total of 91 PAH patients (34 ± 12 years old, 25 males) were enrolled, among which, 42 were classified into low risk group, while 49 were intermediate-high risk group. Compared with low-risk patients, those with intermediate-high risk had significantly larger 3DE-RV volumes, worse ejection fraction (EF) and tricuspid annular plane systolic excursion, and decreased longitudinal strain (LS). Receive operating characteristic curves illustrated all the 3DE parameters were able to predict intermediate-high risk stratification, especially 3D-RVEF (area under curve, 0.82, 95% CI 0.73-0.91, P < 0.001). And 3D-RVEF < 26.39% had a 81.6% sensibility and 73.8% specificity to predict intermediate-high risk stratification. Univariate and multivariate Logistic regression analyses identified 3D-RV end-diastolic (OR 1.02, 95% CI 1.01-1.03, P = 0.002) and end-systolic (OR 1.03, 95% CI 1.01-1.04, P < 0.001) volumes, 3D-RVEF (OR 0.82, 95% CI 0.75-0.90, P < 0.001) and LS of free wall (OR 1.17, 95% CI 1.05-1.31, P = 0.005) as independent predictors of intermediate-high risk stratification. In conclusion, RV volumes, EF and free wall strain detected by 3DE were independent predictors of intermediate-high risk stratification in PAH patients, among which, RVEF showed the best predictive capacity.

[The Clinical Value of the Pathophysiology Oriented Critical Care Ultrasound Exam (POCCUE) Protocol in Acute Respiratory and Circulatory Compromise of Critically Ill Patients].

OBJECTIVE: The aim of this study is to explore the diagnostic and therapeutic accuracy of pathophysiology and clinic oriented critical care ultrasound exam (POCCUE) protocol in acute respiratory and circulatory compromise of critically ill patients. METHODS: Prospectively included patients with acute respiratory and circulatory compromise from ICU of West China Hospital of Sichuan University from March to April 2018. The POCCUE protocol designed according to the pathophysiological changes of acute respiratory and circulatory disorders includes: the first part is the acquiring an ultrasound section and measuring corresponding indicators including pulmonary and echocardiographic indicators; the second part is a comprehensive analysis according to the former examination which evaluates the pathophysiological changes of acute respiratory and circulatory disorders, and then establish the initial etiology diagnosis and start treatment. The clinical value of the POCCUE protocol, including the accuracy of diagnosis, and the differences in treatment was verified by comparing the clinical outcome with the traditional treatment group. RESULTS: A total of 82 subjects were used for statistics. Compare with the traditional group, POCCUE can notably increase the diagnostic and therapeutic accuracy of clinic and pathophysiology (diagnostic accuracy: 93.90% vs. 68.29%, P < 0.01; therapeutic accuracy: 93.90% vs. 62.20%, P < 0.01). CONCLUSION: The POCCUE has a higher accuracy of diagnosis and treatment for patients with acute respiratory and circulatory compromise.

Impact of right ventricular dyssynchrony on prognosis of patients with idiopathic pulmonary arterial hypertension.

Idiopathic pulmonary arterial hypertension is a progressive disease with high mortality with an increasing burden of right ventricular. Right ventricular dyssynchrony was observed in idiopathic pulmonary arterial hypertension, but the association with mortality is unclear. This study aimed to investigate the impact of right ventricular dyssynchrony on the survival of idiopathic pulmonary arterial hypertension. A total of 116 patients with idiopathic pulmonary arterial hypertension were enrolled in this study. All these patients underwent comprehensive clinical evaluation. Right ventricular dyssynchrony was assessed by two-dimensional speckle-tracking echocardiography. The time to peak strain (Tpeak) of right ventricular segments were obtained. Right ventricular dyssynchrony was quantified by the standard deviation of the heart rate-corrected Tpeak of right ventricular four segments. All patients were followed up and the primary endpoint was all cause of death. Results found patients with significant right ventricular dyssynchrony present with advanced World Health Organization functional class, worse hemodynamic status and right ventricular function. Right ventricular dyssynchrony was an independent predictive factor for the survival of idiopathic pulmonary arterial hypertension. Kaplan-Meier survival curves showed patients with right ventricular dyssynchrony had worse prognosis. In conclusion, right ventricular dyssynchrony analyzed by speckle-tracking echocardiography provided added value to hemodynamic and echocardiographic parameters in evaluating the survival of patients with idiopathic pulmonary arterial hypertension.

Identification and characterization of a novel group of natural anti-sense transcripts from RNA1.2 gene locus of human cytomegalovirus.

BACKGROUND: Natural anti-sense transcripts (NATs), which are transcribed from the complementary DNA strand of annotated genes, exert regulatory function of gene expression. Increasing studies recognized anti-sense transcription widespread throughout human cytomegalovirus (HCMV) genome, whereas the anti-sense transcription of RNA1.2 gene locus has never been investigated. In this study, the transcription of the RNA1.2 anti-sense strand was investigated in clinically isolated HCMV strain. METHODS: Strand-specific high-through RNA-sequencing (RNA-seq) was performed to find possible anti-sense transcripts (ASTs). For analyzing and visualization of RNA-seq data sets, Integrative Genomics Viewer software was applied. To confirm these possibilities, Northern blotting and rapid amplification of cDNA ends (RACE) were used. RESULTS: Transcription of the opposite strand of RNA1.2 gene locus was detected by RNA-sequencing using RNAs extracted from human embryonic lung fibroblasts infected with HCMV clinical isolate HAN. At least three HCMV NATs, named RNA1.2 AST 1, RNA1.2 AST2, and RNA1.2 AST3, were characterized by Northern blotting and RACE analyses. These RNA1.2 ASTs orientated from the complementary strand of RNA1.2 locus during the late phase of HCMV infection. The 5'- and 3'-termini of these transcripts were located within the opposite sequence of the predicted RNA1.2 gene. CONCLUSION: A cluster of novel NATs was transcribed from the opposite sequence of the HCMV RNA1.2 gene region.

The Effects of CYP3A5 Genetic Polymorphisms on Serum Tacrolimus Dose-Adjusted Concentrations and Long-Term Prognosis in Chinese Heart Transplantation Recipients.

BACKGROUND AND OBJECTIVES: Effective management of immunosuppressants is extemely important to improve prognosis of heart transplant recipients. We aim to investigate the effects of cytochrome P450 (CYP) 3A5 (rs776746) single nucleotide polymorphisms (SNPs) on serum tacrolimus concentrations/doses (C/Ds, ng/mL per mg/kg) and long-term prognosis in Chinese heart transplant recipients. METHODS: We detected the CYP3A5 SNPs of 203 consecutive Chinese heart transplant recipients between August 2005 and July 2012, and 55 of them who received tacrolimus-based immunosuppressive therapy were enrolled in this study. The tacrolimus C/Ds at 1, 3, 6, 12, 24 and 36 months after transplantation were routinely calculated. X-ray-guided endomyocardial biopsies (EMBs) were performed at 1, 3 and 6 months after heart transplantion to evaluate acute rejection degrees. All participants were then followed up annually until May 2018. The designed primary endpoint was all-cause mortality. RESULTS: In 55 heart transplant recipients (43 males and 12 females), CYP3A5 non-expressors (CYP3A5*3/*3, n = 40) had significantly higher tacrolimus C/Ds than expressors (CYP3A5*1/*3, n = 15) at all time points (P < 0.001). Chi-squared test showed no significant differences in EMB-proven acute rejections between the two groups within 6 months after heart transplantion. The median follow-up period was 94.7 months, and eight patients died. Kaplan-Meier analysis showed CYP3A5 expressors tend to have higher mortality than non-expressors (20% vs 12.5%, log-rank: P = 0.314). CONCLUSIONS: CYP3A5 SNPs affect tacrolimus pharmacokinetics in Chinese heart transplant recipients, and non-expressors have higher tacrolimus C/Ds. In addition, expressors tend to have a worse long-term prognosis than non-expressors.

Two-dimensional speckle tracking echocardiography assessed right ventricular function and exercise capacity in pre-capillary pulmonary hypertension.

Resting two-dimensional speckle tracking echocardiography (2D-STE) identified right ventricular (RV) systolic function were reported to predict exercise capacity in pulmonary hypertension (PH) patients, but little attention had been payed to 2D-STE detected RV diastolic function. Therefore, we aim to elucidate and compare the relations between 2D-STE identified RV diastolic/systolic functions and peak oxygen consumption (PVO2) determined by cardiopulmonary exercise testing (CPET) in pre-capillary PH. 2D-STE was performed in 66 pre-capillary PH patients and 28 healthy controls. Linear correlation and multivariate regression analyses were performed to evaluate and compare the relations between RV 2D-STE parameters and PVO2. Receiver operating characteristic curves were used to compare the predictive value of 2D-STE parameters in predicting the cut-off-PVO2 < 11 ml/min/kg. There were significant differences of all the 2D-STE parameters between PH patients and healthy controls. In patients, RV-peak global longitudinal strain (GLS, rs = - 0.498, P < 0.001), RV- peak systolic strain rate (GSRs, rs = - 0.537, P < 0.001) and RV- peak early diastolic strain rate (GSRe, rs = 0.527, P < 0.001) significantly correlated with PVO2, but no significant correlation was observed between RV- peak late diastolic strain rate (GSRa, rs = 0.208, P = 0.093) and PVO2. The first multivariate regression analysis of clinical data without echocardiographic parameters identified WHO functional class, NT-proBNP and BMI as independent predictors of PVO2 (Model-1, adjusted r2 = 0.421, P < 0.001); Then we added conventional echocardiographic parameters and 2D-STE parameters to the clinical data, identified S,(Model-2,adjusted r2 = 0.502, P < 0.001), RV-GLS (Model-3, adjusted r2 = 0.491, P < 0.001), RV-GSRe (Model-4, adjusted r2 = 0.500, P < 0.001) and RV-GSRs (Model-5, adjusted r2 = 0.519, P < 0.001) as independent predictors of PVO2, respectively. The predictive power was increased, and Model-5 including RV-GSRs showed the highest predictive capability. ROC curves found RV-GSRs expressed the strongest predictive value (AUC = 0.88, P < 0.001), and RV-GSRs > - 0.65/s had a 88.2% sensibility and 82.2% specificity to predict PVO2 < 11 ml/min/kg. 2D-STE assessed RV function improves the prediction of exercise capacity represented by PVO2 in pre-capillary PH.

Comparison of the capability of risk stratification evaluation between two- and three-dimensional speckle-tracking strain in pre-capillary pulmonary hypertension.

To investigate and compare the value of right ventricular longitudinal strain detected by two-dimensional and three-dimensional speckle-tracking echocardiography in risk stratification evaluation in pre-capillary pulmonary hypertension. We consecutively screened 66 patients diagnosed with pre-capillary pulmonary hypertension in our center. According to the risk assessment recommended by 2015 European Society of Cardiology Guidelines, all participants were classified into low- and intermediate-high-risk group. Two-dimensional and three-dimensional strains were measured using off-line softwares (GE EchoPAC version 201 and TomTec, 4D RV Function 2.0). Fifty-seven pre-capillary pulmonary hypertension patients (average 35 years old, 18 males and 39 females) were finally enrolled in our study, 32 (56.1%) were classified in low-risk group, while 25 (43.9%) were in the intermediate-high-risk group. Clinical data associated with disease severity, such as N-terminal pro-brain natriuretic peptide (r = 0.574, P < 0.001), peak oxygen consumption (r = -0.484, P < 0.001), and 6-min walking distance (r = -0.356, P = 0.008) were significantly correlated with two-dimensional right ventricular longitudinal strain; while the correlations with three-dimensional right ventricular longitudinal strain were weaker. Receiver operating characteristic curves for the detection of intermediate-high risk stratification showed two-dimensional right ventricular longitudinal strain had the best predictive capacity (area under curve, 0.82, 95% CI: 0.71-0.93, P < 0.001). Univariate and Multivariate Logistic regression analyses identified two-dimensional right ventricular longitudinal strain as an independent predictor (OR: 1.42, 95% CI: 1.18-1.71, P < 0.001) of intermediate-high risk stratification in this cohort of pre-capillary pulmonary hypertension patients, the predictive capacity retained (OR: 1.45, 95% CI: 1.18-1.78, P < 0.001) after adjusted by age, gender, and body mass index, while three-dimensional speckle-tracking echocardiography parameters were not. In conclusion, when used for the detection of intermediate-high risk stratification in pre-capillary pulmonary hypertension, two-dimensional right ventricular longitudinal strain was better than three-dimensional right ventricular longitudinal strain.