Imaging of cardiac fibroblast activation in patients with chronic thromboembolic pulmonary hypertension.

PURPOSE: The aim of this study was to explore the association of cardiac fibroblast activation with clinical parameters and cardiovascular magnetic resonance (CMR) imaging parameters in patients with chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: Thirteen CTEPH patients were prospectively enrolled. All of the patients underwent cardiac 68Gallium-labelled fibroblast activation protein inhibitor (68 Ga-FAPI-04)-positron emission tomography/computed tomography (PET/CT), right heart catheterisation, and echocardiography, and 11 of them additionally underwent CMR. Thirteen control subjects were selected to establish the normal range of cardiac 68 Ga-FAPI-04 uptake. Cardiac 68 Ga-FAPI-04 uptake higher than that in the blood pool was defined as abnormal. The global and segmental maximum standardised uptake values (SUVmax) of the right ventricle (RV) were measured and further expressed as target-to-background ratio (TBRRV) with left ventricular lateral wall activity as background. Late gadolinium enhancement (LGE) was visually evaluated, and native-T1 times, enhanced-T1 times, and extracellular volume (ECV) were quantitatively measured. RESULTS: Ten CTEPH patients (77%) had abnormal 68 Ga-FAPI-04 uptake in RV, mainly located in the free wall, which was significantly higher than that in controls (TBRRV: 2.4 ± 0.9 vs 1.0 ± 0.1, P < 0.001). The TBRRV correlated positively with the thickness of RV wall (r = 0.815, P = 0.001) and inversely with RV fraction area change (RVFAC) (r = - 0.804, P = 0.001) and tricuspid annular plane systolic excursion (TAPSE) (r = - 0.678, P = 0.011). No correlation was found between 68 Ga-FAPI-04 activity and CMR imaging parameters. CONCLUSION: Fibroblast activation in CTEPH, measured by 68 Ga-FAPI-04 imaging, is mainly localised in the RV free wall. Enhanced fibroblast activation reflects the thickening of the RV wall and decreased RV contractile function.

Clinical Features and Outcomes of Pulmonary Artery Sarcoma.

OBJECTIVES: A retrospective cohort study was designed to describe the clinical features and outcomes of pulmonary artery sarcoma (PAS). METHODS: Twenty-two (22) consecutive patients diagnosed with PAS by pathological examination were enrolled and followed up until they died or until January 2020. The medical records were retrospectively reviewed to evaluate the clinical characteristics, image findings, and outcomes. RESULTS: 1) Twenty-one (21, 95.5%) patients were firstly misdiagnosed. Dyspnoea was the most common presenting symptom (19 of 22, 86.4%). 2) Filling defects in the right pulmonary artery were seen in 17 patients (77.3%) with computed tomography pulmonary angiography or magnetic resonance pulmonary angiography. Among those patients, 14 underwent positron emission tomography-computed tomography detection and 13 (92.9%) were found to have increased uptake value in the pulmonary artery. 3) The median survival (from diagnosis to death or January 2020) of the total series was 11.6 months (range, 0.7-68.5 months). The estimated cumulative survival rates at 1, 2, and 3 years were 52.6%, 32.8%, and 19.7%, respectively. Patients who received surgery and/or chemo-radiotherapy treatment had a better survival rate compared with patients without treatment (the estimated cumulative survival rates at 1, 2, and 3 years were 60.3%, 39.1%, and 29.3%, respectively, vs 33.3%, 16.6%, and 0, accordingly) and better survival time (median survival 17.02 vs 3.16 months, respectively) (p=0.025). CONCLUSIONS: Pulmonary artery sarcoma is easily misdiagnosed, as the symptoms and routine image detection are nonspecific. Positron emission tomography-computed tomography may be helpful in diagnosis. Surgery and/or chemo-radiotherapy offer a chance for better outcomes.

Arabidopsis GDSL1 overexpression enhances rapeseed Sclerotinia sclerotiorum resistance and the functional identification of its homolog in Brassica napus.

Sclerotinia stem rot (SSR) caused by Sclerotinia sclerotiorum is a devastating disease of rapeseed (Brassica napus L.). To date, the genetic mechanisms of rapeseed' interactions with S. sclerotiorum are not fully understood, and molecular-based breeding is still the most effective control strategy for this disease. Here, Arabidopsis thaliana GDSL1 was characterized as an extracellular GDSL lipase gene functioning in Sclerotinia resistance. Loss of AtGDSL1 function resulted in enhanced susceptibility to S. sclerotiorum. Conversely, overexpression of AtGDSL1 in B. napus enhanced resistance, which was associated with increased reactive oxygen species (ROS) and salicylic acid (SA) levels, and reduced jasmonic acid levels. In addition, AtGDSL1 can cause an increase in lipid precursor phosphatidic acid levels, which may lead to the activation of downstream ROS/SA defence-related pathways. However, the rapeseed BnGDSL1 with highest sequence similarity to AtGDSL1 had no effect on SSR resistance. A candidate gene association study revealed that only one AtGDSL1 homolog from rapeseed, BnaC07g35650D (BnGLIP1), significantly contributed to resistance traits in a natural B. napus population, and the resistance function was also confirmed by a transient expression assay in tobacco leaves. Moreover, genomic analyses revealed that BnGLIP1 locus was embedded in a selected region associated with SSR resistance during the breeding process, and its elite allele type belonged to a minor allele in the population. Thus, BnGLIP1 is the functional equivalent of AtGDSL1 and has a broad application in rapeseed S. sclerotiorum-resistance breeding.

A New TBX5 Loss-of-Function Mutation Contributes to Congenital Heart Defect and Atrioventricular Block.

Congenital heart defect (CHD) represents the most common birth deformity, afflicting 1% of all births worldwide, and accounts for substantial morbidity and mortality. Increasing evidence highlights the pivotal roles of genetic etiologies in the pathogenesis of CHD, and pathogenic mutations in multiple genes, including TBX5 encoding a cardiac core transcription factor key to cardiovascular morphogenesis, have been involved in CHD. However, due to pronounced genetic heterogeneity of CHD, the genetic determinants underlying CHD in most cases remain obscure. In this investigation, by sequencing analysis of the coding exons and flanking introns of the TBX5 gene in 198 unrelated patients affected with CHD, a novel heterozygous mutation, NM_000192.3: c.692C>T; p. (Pro231Leu), was identified in an index patient with familial double outlet right ventricle (DORV), ventricular septal defect (VSD), and atrioventricular block (AVB). Genetic analysis of the proband's pedigree showed that the mutation co-segregated with the diseases. The missense mutation, which altered the amino acid conserved evolutionarily, was absent from 266 unrelated healthy subjects. Functional analyses with a dual-luciferase reporter assay system unveiled that the Pro231Leu-mutant TBX5 was associated with significantly reduced transcriptional activity on its target genes MYH6 and NPPA. Furthermore, the mutation disrupted the synergistic transactivation between TBX5 and NKX2-5 as well as GATA4, two other transcription factors causally linked to CHD. This study firstly links TBX5 loss-of-function mutation to familial DORV, VSD, and AVB, which provides novel insight into the mechanism underpinning CHD and AVB, suggesting potential implications for genetic evaluation and individualized treatment of patients affected by CHD and AVB.

Correction to: Multiple cardiovascular involvements in Behçet's disease: unique utility of 18F-FDG PET/CT in diagnosis and follow-up.

Figure c of the original version of this article was not converted properly. Correct figure is presented here. The original article has been corrected.

Improving seed germination and oil contents by regulating the GDSL transcriptional level in Brassica napus.

KEY MESSAGE: Seed germination rate and oil content can be regulated at theGDSL transcriptional level by eitherAtGDSL1 orBnGDSL1 inB. napus. Gly-Asp-Ser-Leu (GDSL)-motif lipases represent an important subfamily of lipolytic enzymes, which play important roles in lipid metabolism, seed development, abiotic stress, and pathogen defense. In the present study, two closely related GDSL-motif lipases, Brassica napus GDSL1 and Arabidopsis thaliana GDSL1, were characterized as functioning in regulating germination rate and seed oil content in B. napus. AtGDSL1 and BnGDSL1 overexpression lines showed an increased seed germination rate and improved seedling establishment compared with wild type. Meanwhile, the constitutive overexpression of AtGDSL1 and BnGDSL1 promoted lipid catabolism and decreased the seed oil content. While RNAi-mediated suppression of BnGDSL1 (Bngdsl1) in B. napus improved the seed oil content and decreased seed germination rate. Moreover, the Bngdsl1 transgenic seeds showed changes in the fatty acid (FA) composition, featuring an increase in C18:1 and a decrease in C18:2 and C18:3. The transcriptional levels of six related core enzymes involved in FA mobilization were all elevated in the AtGDSL1 and BnGDSL1 overexpression lines, but strongly suppressed in the Bngdsl1 transgenic line. These results suggest that improving the seed germination and seed oil content in B. napus could be achieved by regulating the GDSL transcriptional level.

A SHOX2 loss-of-function mutation underlying familial atrial fibrillation.

Atrial fibrillation (AF), as the most common sustained cardiac arrhythmia, is associated with substantially increased morbidity and mortality. Aggregating evidence demonstrates that genetic defects play a crucial role in the pathogenesis of AF, especially in familial AF. Nevertheless, AF is of pronounced genetic heterogeneity, and in an overwhelming majority of cases the genetic determinants underlying AF remain elusive. In the current study, 162 unrelated patients with familial AF and 238 unrelated healthy individuals served as controls were recruited. The coding exons and splicing junction sites of the SHOX2 gene, which encodes a homeobox-containing transcription factor essential for proper development and function of the cardiac conduction system, were sequenced in all study participants. The functional effect of the mutant SHOX2 protein was characterized with a dual-luciferase reporter assay system. As a result, a novel heterozygous SHOX2 mutation, c.580C>T or p.R194X, was identified in an index patient, which was absent from the 476 control chromosomes. Genetic analysis of the proband's pedigree revealed that the nonsense mutation co-segregated with AF in the family with complete penetrance. Functional assays demonstrated that the mutant SHOX2 protein had no transcriptional activity compared with its wild-type counterpart. In conclusion, this is the first report on the association of SHOX2 loss-of-function mutation with enhanced susceptibility to familial AF, which provides novel insight into the molecular mechanism underpinning AF, suggesting potential implications for genetic counseling and individualized management of AF patients.

Differential Diagnosis of Pulmonary Artery Sarcoma and Central Chronic Pulmonary Thromboembolism Using CT and MR Images.

BACKGROUND: Clinical and imaging manifestations are similar in pulmonary artery sarcomas (PAS) and thromboembolic diseases, especially central chronic pulmonary thromboembolism (CPTE). The feasibility of utilising clinical imaging tools such as computed tomography (CT) and magnetic resonance imaging (MRI) for differential diagnosis of PAS and CPTE has not been fully explored, especially MRI. METHODS: Patients with PAS (n=18) and central CPTE (n=20) treated at our hospital between January 2013 and September 2016 were identified retrospectively. Computed tomography and MRI findings of pulmonary artery (PA) filling defects including the location, the involvement of pulmonary artery, morphology, signal intensities and enhancement in MRI, calcification, sizes of right atrium and ventricle, inner diameters of the pulmonary artery trunk and branches, and mediastinal collateral circulation in both groups were examined, and differences were analysed by Fisher exact test and independent sample t-test. RESULTS: Compared to those of central CPTE, PAS lesions were in full shape or expansive growth (p<0.001), and the proximal end of the tumours was often bulging or lobulated (p<0.001). These lesions were aneurysm- or grape-like distally (p<0.01) with inhomogeneous enhancement (p<0.001). The MRI contrast enhancement pattern of PAS lesions were cloudy with inhomogeneous delayed enhancement and the time-density curves for some of the lesions increased gradually. CONCLUSION: Computed tomographic and MR imaging manifestations may resemble PAS and central CPTE; however, some manifestations still have great value for the differential diagnosis of these two conditions, specifically the morphology and MRI enhancement patterns.

Disconnections of Cortico-Subcortical Pathways Related to Cognitive Impairment in Patients with Leukoaraiosis: A Preliminary Diffusion Tensor Imaging Study.

BACKGROUND: We aimed to explore the relation between the microstructural integrity of white matter using the technique of diffusion tensor imaging (DTI) and changes of cognition in leukoaraiosis (LA). METHODS: Fifty patients with LA and 50 age- and gender-matched controls were recruited consecutively. The average values of mean diffusivity (MD) and fractional anisotropy (FA) were quantified both within white matter lesions (WMLs) and normal-appearing white matter (NAWM) from the regions of interest (ROIs). RESULTS: We found significantly decreased FA and increased MD in WMLs at the 5 ROIs than that in NAWM and controls (p < 0.05). The values of FA in NAWM were significantly lower at centrum semiovale and posterior periventricular white matter than those of controls (p < 0.05). The values of MD in NAWM were significantly higher at the anterior periventricular white matter and corpus callosum than those of controls (p < 0.05). The values of FA in NAWM located at anterior periventricular white matter correlated inversely with the Z scores of executive function (r = -0.420, p = 0.028). CONCLUSIONS: DTI may provide some important information about the cognitive dysfunction in patients with LA, which may largely attribute to the "disconnection" of cortico-subcortical pathways, with the evidence of reduced FA and increased MD.

Application of a hospital-community-family trinity rehabilitation nursing model combined with motor imagery therapy in patients with cerebral infarction.

BACKGROUND: Rehabilitation nursing is considered an indispensable part of the cerebral infarction treatment system. The hospital-community-family trinity rehabilitation nursing model can provide continuous nursing services across hospitals, communities, and families for patients. AIM: To explore the application of a hospital-community-family rehabilitation nursing model combined with motor imagery therapy in patients with cerebral infarction. METHODS: From January 2021 to December 2021, 88 patients with cerebral infarction were divided into a study (n = 44) and a control (n = 44) group using a simple random number table. The control group received routine nursing and motor imagery therapy. The study group was given hospital-community-family trinity rehabilitation nursing based on the control group. Motor function (FMA), balance ability (BBS), activities of daily living (BI), quality of life (SS-QOL), activation status of the contralateral primary sensorimotor cortical area to the affected side, and nursing satisfaction were evaluated before and after intervention in both groups. RESULTS: Before intervention, FMA and BBS were similar (P > 0.05). After 6 months' intervention, FMA and BBS were significantly higher in the study than in the control group (both P < 0.05). Before intervention, BI and SS-QOL scores were not different between the study and control group (P > 0.05). However, after 6 months' intervention, BI and SS-QOL were higher in the study than in the control group (P < 0.05). Before intervention, activation frequency and volume were similar between the study and the control group (P > 0.05). After 6 months' intervention, the activation frequency and volume were higher in the study than in the control group (P < 0.05). The reliability, empathy, reactivity, assurance, and tangibles scores for quality of nursing service were higher in the study than in the control group (P < 0.05). CONCLUSION: Combining a hospital-community-family trinity rehabilitation nursing model and motor imagery therapy enhances the motor function and balance ability of patients with cerebral infarction, improving their quality of life.

Analysis of clinical features between active and inactive patients of Takayasu's arteritis with pulmonary arteries involvement.

BACKGROUND: The aim of this study was to investigate the clinical characteristics of patients between active and inactive Takayasu's arteritis with pulmonary artery involvement (PTA) and to identify better markers of disease activity in these patients. METHODS: Sixty-four PTA patients in Beijing Chao-yang hospital (2011 to 2021) were included. According to National Institutes of Health criteria, 29 patients were in active stage and 35 were in inactive stage. Their medical records were collected and analyzed. RESULTS: Compared with inactive group, patients in active group were younger. More patients in active stage presented fever (41.38% vs 5.71%), chest pain (55.17% vs 20%), increased C-reactive protein (2.91 vs 0.46 mg/L), erythrocyte sedimentation rate (35.0 vs 9 mm/h), and platelet count (291 vs 221 × 109/L). Pulmonary artery wall thickening was more common in active group (51.72% vs 11.43%). These parameters were restored after treatment. The incidence of pulmonary hypertension was comparable between groups (34.48% vs 51.43%), but patients in active group had lower pulmonary vascular resistance (PVR) (361.0 vs 891.0 dyn·s·cm-5) and higher cardiac index (2.76 ± 0.72 vs 2.01 ± 0.58 L/min/m2). On multivariate logistic regression analysis, chest pain [odds ratio (OR) 9.37, 95%CI (1.98-44.38), P = 0.005], increased platelet count (>242.5 × 109/L) [OR 9.03, 95%CI (2.10-38.87), P = 0.003] and pulmonary artery wall thickening [OR 7.08, 95%CI (1.44-34.89), P = 0.016] were independently associated with disease activity. CONCLUSION: Chest pain, increased platelet count, and pulmonary artery wall thickening are potential new indicators of disease activity in PTA. Patients in active stage may have lower PVR and better right heart function.

Discovery of TBX20 as a Novel Gene Underlying Atrial Fibrillation.

Atrial fibrillation (AF), the most prevalent type of sustained cardiac dysrhythmia globally, confers strikingly enhanced risks for cognitive dysfunction, stroke, chronic cardiac failure, and sudden cardiovascular demise. Aggregating studies underscore the crucial roles of inherited determinants in the occurrence and perpetuation of AF. However, due to conspicuous genetic heterogeneity, the inherited defects accounting for AF remain largely indefinite. Here, via whole-genome genotyping with genetic markers and a linkage assay in a family suffering from AF, a new AF-causative locus was located at human chromosome 7p14.2-p14.3, a ~4.89 cM (~4.43-Mb) interval between the markers D7S526 and D7S2250. An exome-wide sequencing assay unveiled that, at the defined locus, the mutation in the TBX20 gene, NM_001077653.2: c.695A>G; p.(His232Arg), was solely co-segregated with AF in the family. Additionally, a Sanger sequencing assay of TBX20 in another family suffering from AF uncovered a novel mutation, NM_001077653.2: c.862G>C; p.(Asp288His). Neither of the two mutations were observed in 600 unrelated control individuals. Functional investigations demonstrated that the two mutations both significantly reduced the transactivation of the target gene KCNH2 (a well-established AF-causing gene) and the ability to bind the promoter of KCNH2, while they had no effect on the nuclear distribution of TBX20. Conclusively, these findings reveal a new AF-causative locus at human chromosome 7p14.2-p14.3 and strongly indicate TBX20 as a novel AF-predisposing gene, shedding light on the mechanism underlying AF and suggesting clinical significance for the allele-specific treatment of AF patients.

Construction of an infectious clone of human adenovirus type 41.

Human adenovirus type 41 (HAdV-41) is well known for its fastidiousness in cell culture. To construct an infectious clone of HAdV-41, a DNA fragment containing the left and right ends of HAdV-41 as well as a kanamycin resistance gene and a pBR322 replication origin was excised from the previously constructed plasmid pAd41-GFP. Using homologous recombination, the plasmid pKAd41 was generated by co-transformation of the E. coli BJ5183 strain with this fragment and HAdV-41 genomic DNA. Virus was rescued from pKAd41-transfected 293TE7 cells, a HAdV-41 E1B55K-expressing cell line. The genomic integrity of the rescued virus was verified by restriction analysis and sequencing. Two fibers on the virion were confirmed by western blot. Immunofluorescence showed that more expression of the hexon protein could be found in 293TE7 cells than in 293 cells after HAdV-41 infection. The feature of non-lytic replication was preserved in 293TE7 cells, since very few progeny HAdV-41 viruses were released to the culture medium. These results show that pKAd41 is an effective infectious clone and suggest that the combination of pKAd41 and 293TE7 cells is an ideal system for virological study of HAdV-41.

[Characteristics of cognitive impairment in patients with leukoaraiosis].

OBJECTIVE: To explore the characteristics of cognitive impairment in patients with leukoaraiosis (LA). METHODS: Forty-six LA patients and 38 age and gender-matched healthy subjects were recruited from the Department of Neurology, Beijing Chaoyang Hospital, Capital Medical University between September 2010 and March 2011. All participants underwent the neuropsychological tests recommended by the National Institute of Neurological Disorders and Stroke-Canadian Stroke Network Vascular Cognitive Impairment Harmonization Standards (NINDS/CSN). The were divided into 3 different groups (mild, moderate and severe) according to the Fazekas scale. The differences of neuropsychological performances were compared among 3 groups. RESULTS: The LA patients were associated with comprehensive cognitive function deficits, including MMSE (24.4 ± 3.2 vs 28.3 ± 1.2), MoCA (20.4 ± 3.0 vs 26.2 ± 0.8), digital span forward (5.7 ± 0.9 vs 6.8 ± 1.0), digital span backward (3.5 ± 0.7 vs 4.1 ± 0.7), Stroop-B (69 ± 13 vs 43 ± 5), Stroop-C (141 ± 42 vs 65 ± 10), trail making test-A (73 ± 15 vs 31 ± 7), trail making test-B (126 ± 18 vs 82 ± 6) and digit symbol test (25 ± 6 vs 37 ± 5, P < 0.05). However, there was no difference in the performance of verbal fluency (12.7 ± 2.5 vs 13.4 ± 2.5, P > 0.05). Correlation analysis showed that the severity of LA had a negative correlation with the performance of MoCA (r = -0.601, P = 0.002). CONCLUSIONS: The LA patients are closely correlated with cognitive impairments of attention, memory, executive function and information processing speed. It may be attributed to the frontal-subcortical circuitry dysfunction.

[Correlates of cognitive impairment in patients with leukoaraiosis by magnetic resonance spectroscopy].

OBJECTIVE: To explore the pathological changes in patients with leukoaraiosis (LA) by magnetic resonance spectroscopy (MRS) and examine its relationship with cognitive function. METHODS: Twenty-three LA patients and 23 age and gender-matched healthy subjects were recruited from the Department of Neurology, Beijing Chaoyang Hospital, Capital Medical University between August 2010 and November 2010. All participants underwent the neuropsychological tests. Multi-voxel chemical shift imaging was performed and the regions of interest were positioned in bilateral frontal white matter. The relative metabolite ratios, involving N-acetyl aspartate/choline ratio (NAA/Cho), N-acetyl aspartate/creatine (NAA/Cr) and choline/creatine (Cho/Cr), were estimated. The correlation of the MRS data and the performance of cognitive function was analyzed. RESULTS: The LA patients were associated with a worse performance of mini mental state examination (MMSE) versus the healthy controls (24 ± 3 vs 28 ± 1, P < 0.05). Univariate analysis of the MRS data revealed the ratios of NAA/Cho and NAA/Cr significantly decreased in bilateral frontal white matter lesions in the LA group versus the control group (1.72 ± 0.20 vs 1.96 ± 0.36, 1.67 ± 0.17 vs 1.85 ± 0.21, P < 0.05). The values of NAA/Cr and NAA/Cho in normal appearing white matter increased versus the LA group (1.83 ± 0.24 vs 1.72 ± 0.20, 1.78 ± 0.28 vs 1.67 ± 0.17) and decreased versus the control group (1.83 ± 0.24 vs 1.96 ± 0.36, 1.78 ± 0.28 vs 1.85 ± 0.21). But no significant differences were found (P > 0.05). The ratio of Cho/Cr did not differ among 3 groups (P > 0.05). The pathological change of NAA/Cr in white matter lesion in LA patients was markedly correlated with the performance of MMSE (r = 0.47, P < 0.05). CONCLUSION: NAA may be a marker of axonal loss/dysfunction in LA patients. And the changes of NAA/Cr have a positive correlation with cognitive impairment.

[Anatomic distribution of embolus at CT pulmonary angiography in patients suspected acute pulmonary embolism].

OBJECTIVE: To summarize and analyse the morphology and distribution of embolus in patients suspected acute pulmonary embolism. METHODS: The CT pulmonary angiography (CTPA) imagings of 279 patients suspected acute pulmonary embolism were analysed retrospectively in Ningxia from January 2004 through June 2006 and in Beijing from September 2005 through October 2006. The incidence of central embolus, peripheral embolus and mixed embolus, and the distribution and the morphology of embolus in different levels of pulmonary arteries were analysed. RESULTS: A total of 279 patients (158 males, 121 females; Median age was 63 years) were recruited. The incidence of central embolus, peripheral embolus and mixed embolus were 3.5%, 40.9% and 55.6%, respectively. There were 1850 emboli found above the segmental pulmonary arterial, 58.2% were found in right pulmonary artery, and 41.8% in left pulmonary artery. For all of the emboli, there were 29.7% in bilateral upper lobes, 18.3% in medial lobe and lingual lobe, and 49.8% in bilateral lower lobes. The percent of A, B and C type embolus were 81.7%, 7.6% and 10.7%, respectively. CONCLUSION: It was not unusual for the peripheral thrombosis, and can be improved to detect peripheral thrombosis by thin-slice CT scan. The distribution of embolus in pulmonary vascular and the distribution of blood flow was consistent, the number of embolus in right lung were more than left lung, and lower lobes more than upper lobes and middle lobes.

[Technical study of vinpocetine micelles prepared by thin-film hydration method].

OBJECTIVE: To prepare PEG-PLA polymeric micelles loaded with vinpocetine (VP). METHODS: VP micelles were prepared by thin-film hydration method, single factors affecting drug loading content, encapsulation efficiency, productivity, particle size and polydispersity index (PDI) such as dosage, type of organic solvent, quantity of organic solvent, hydration temperature, hydration speed, amount of hydration water, hydration time were investigated, and the optimum technology was obtained. The mean particle size and PDI were determined by DLS. The drug loading content, encapsulation efficiency, productivity of VP micelles were investigated by UV. RESULTS: The drug loading content and particle size of VP micelles were 20.35% and 118.3 nm, respectively. CONCLUSION: The technology of VP micelles prepared by thin-film hydration method is practical and simple. It's valuable to be further studied.

KLF13 Loss-of-Function Mutations Underlying Familial Dilated Cardiomyopathy.

Background Dilated cardiomyopathy (DCM), characterized by progressive left ventricular enlargement and systolic dysfunction, is the most common type of cardiomyopathy and a leading cause of heart failure and cardiac death. Accumulating evidence underscores the critical role of genetic defects in the pathogenesis of DCM, and >250 genes have been implicated in DCM to date. However, DCM is of substantial genetic heterogeneity, and the genetic basis underpinning DCM remains elusive in most cases. Methods and Results By genome-wide scan with microsatellite markers and genetic linkage analysis in a 4-generation family inflicted with autosomal-dominant DCM, a new locus for DCM was mapped on chromosome 15q13.1-q13.3, a 4.77-cM (≈3.43 Mbp) interval between markers D15S1019 and D15S1010, with the largest 2-point logarithm of odds score of 5.1175 for the marker D15S165 at recombination fraction (θ)=0.00. Whole-exome sequencing analyses revealed that within the mapping chromosomal region, only the mutation in the KLF13 gene, c.430G>T (p.E144X), cosegregated with DCM in the family. In addition, sequencing analyses of KLF13 in another cohort of 266 unrelated patients with DCM and their available family members unveiled 2 new mutations, c.580G>T (p.E194X) and c.595T>C (p.C199R), which cosegregated with DCM in 2 families, respectively. The 3 mutations were absent from 418 healthy subjects. Functional assays demonstrated that the 3 mutants had no transactivation on the target genes ACTC1 and MYH7 (2 genes causally linked to DCM), alone or together with GATA4 (another gene contributing to DCM), and a diminished ability to bind the promoters of ACTC1 and MYH7. Add, the E144X-mutant KLF13 showed a defect in intracellular distribution. Conclusions This investigation indicates KLF13 as a new gene predisposing to DCM, which adds novel insight to the molecular pathogenesis underlying DCM, implying potential implications for prenatal prevention and precision treatment of DCM in a subset of patients.