The management pattern and outcomes of chronic thromboembolic pulmonary hypertension: rationale and design for a Chinese real-world study.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive pulmonary vascular disorder with substantial morbidity and mortality, also a disease underdiagnosed and undertreated. It is potentially curable by pulmonary endarterectomy (PEA) in patients with surgically accessible thrombi. Balloon pulmonary angioplasty (BPA) and targeted medical therapy are options for patients with distal lesions or persistent/recurrent pulmonary hypertension after PEA. There is an urgent need to increase the awareness of CTEPH. Qualified CTEPH centers are still quite limited. Baseline characteristics, management pattern and clinical outcome of CTEPH in China needs to be reported. METHODS AND DESIGN: The CHinese reAl-world study to iNvestigate the manaGEment pattern and outcomes of chronic thromboembolic pulmonary hypertension (CHANGE) study is designed to provide the multimodality treatment pattern and clinical outcomes of CTEPH in China. Consecutive patients who are ≥ 14 year-old and diagnosed with CTEPH are enrolled. The diagnosis of CTEPH is confirmed in right heart catheterization and imaging examinations. The multimodality therapeutic strategy, which consists of PEA, BPA and targeted medical therapy, is made by a multidisciplinary team. The blood sample and tissue from PEA are stored in the central biobank for further research. The patients receive regular follow-up every 3 or 6 months for at least 3 years. The primary outcomes include all-cause mortality and changes in functional and hemodynamic parameters from baseline. The secondary outcomes include the proportion of patients experiencing lung transplantation, the proportion of patients experiencing heart and lung transplantation, and changes in health-related quality of life. Up to 31 December 2023, the study has enrolled 1500 eligible patients from 18 expert centers. CONCLUSIONS: As a real-world study, the CHANGE study is expected to increase our understanding of CTEPH, and to fill the gap between guidelines and the clinical practice in the diagnosis, assessment and treatment of patients with CTEPH. REGISTRATION NUMBER IN CLINICALTRIALS.GOV: NCT05311072.

H3K18 lactylation of senescent microglia potentiates brain aging and Alzheimer's disease through the NFκB signaling pathway.

Cellular senescence serves as a fundamental and underlying activity that drives the aging process, and it is intricately associated with numerous age-related diseases, including Alzheimer's disease (AD), a neurodegenerative aging-related disorder characterized by progressive cognitive impairment. Although increasing evidence suggests that senescent microglia play a role in the pathogenesis of AD, their exact role remains unclear. In this study, we quantified the levels of lactic acid in senescent microglia, and hippocampus tissues of naturally aged mice and AD mice models (FAD4T and APP/PS1). We found lactic acid levels were significantly elevated in these cells and tissues compared to their corresponding counterparts, which increased the level of pan histone lysine lactylation (Kla). We aslo identified all histone Kla sites in senescent microglia, and found that both the H3K18 lactylation (H3K18la) and Pan-Kla were significantly up-regulated in senescent microglia and hippocampus tissues of naturally aged mice and AD modeling mice. We demonstrated that enhanced H3K18la directly stimulates the NFκB signaling pathway by increasing binding to the promoter of Rela (p65) and NFκB1(p50), thereby upregulating senescence-associated secretory phenotype (SASP) components IL-6 and IL-8. Our study provides novel insights into the physiological function of Kla and the epigenetic regulatory mechanism that regulates brain aging and AD. Specifically, we have identified the H3K18la/NFκB axis as a critical player in this process by modulating IL-6 and IL-8. Targeting this axis may be a potential therapeutic strategy for delaying aging and AD by blunting SASP.

Long-Term Results and Risk Factors of Treatment for Post-Infarction Ventricular Septal Rupture: A Single-Center Experience.

BACKGROUND: Ventricular septal rupture (VSR) following myocardial infarction (MI) is a rare but lethal complication. We analyzed the long-term results and risk factors for survival in the treatment of VSR. METHODS: From January 2012 to December 2021, 115 consecutive patients with post-MI VSR were admitted to our hospital. Depending on different treatment methods patients were divided into following three groups: medical, transcatheter intervention, and surgical repair. During the study, relevant clinical data, operation-related conditions, and follow-up data were analyzed. The Kaplan-Meier method and log-rank test were used to determine the cumulative incidence of mortality. The independent risk factors for patient mortality were evaluated by multivariate logistic regression. RESULTS: The mean follow-up time was 43.4 ± 34.7 months. The overall in-hospital, 30-day, and long-term mortality rates were 24.3%, 38.3%, and 51.3%, respectively. In the medical group, the in-hospital and 30-day mortality rates were 46.7 % (21/45) and 82.2 % (37/45), respectively, with only three patients alive at follow-up. In the transcatheter intervention group, 30-day and long-term mortality rates were 12% and 28%, respectively. In the surgical repair group, 30-day and long-term mortality rates were 8.9% and 22.2%, respectively. Compared with the surgery-group patients, patients with transcatheter intervention had a longer time from VSR to intervention. Logistic regression analysis revealed that age, previous infarction, Killip class, serum creatinine, Troponin T, N-terminal pro-B-type natriuretic peptide, and medical strategy were risk factors for all-cause mortality. CONCLUSIONS: The 30-day and long-term outcomes of patients treated with surgical repair and transcatheter intervention were significantly better than medically treated patients.

Iatrogenic or predetermined aortic dysplasia?

Coarctation of aorta post-transcatheter occlusion of patent ductus arteriosus is rare. We report a special case of infant with patent ductus arteriosus complicated by bicuspid aortic valve, who presented severe coarctation of aorta and aortic valve dysfunction post-patent ductus arteriosus occlusion during follow-up, eventually receiving surgical operations. A genetic rather than iatrogenic predisposition towards post-procedural complications has been discussed.

Spontaneous massive intracystic hemorrhage due to cystic hemangioblastoma in a pediatric patient.

Massive cerebellar hemorrhage from hemangioblastomas in children has never been described to our knowledge. We reported a 10-year-old child who presented with a large hematoma in the left cerebellar hemisphere. Hemangioblastomas was not expected preoperatively to be the cause. An emergency suboccipital craniotomy was performed. Histopathological examination confirmed the diagnosis of hemangioblastoma with massive hemorrhage.

Cyanidin-3-O-glucoside Contributes to Leaf Color Change by Regulating Two bHLH Transcription Factors in Phoebe bournei.

Anthocyanins produce different-colored pigments in plant organs, which provide ornamental value. Thus, this study was conducted to understand the mechanism of anthocyanin synthesis in ornamental plants. Phoebe bournei, a Chinese specialty tree, has high ornamental and economic value due to its rich leaf color and diverse metabolic products. Here, the metabolic data and gene expression of red P. bournei leaves at the three developmental stages were evaluated to elucidate the color-production mechanism in the red-leaved P. bournei species. First, metabolomic analysis identified 34 anthocyanin metabolites showing high levels of cyanidin-3-O-glucoside (cya-3-O-glu) in the S1 stage, which may suggest that it is a characteristic metabolite associated with the red coloration of the leaves. Second, transcriptome analysis showed that 94 structural genes were involved in anthocyanin biosynthesis, especially flavanone 3'-hydroxy-lase (PbF3'H), and were significantly correlated with the cya-3-O-glu level. Third, K-means clustering analysis and phylogenetic analyses identified PbbHLH1 and PbbHLH2, which shared the same expression pattern as most structural genes, indicating that these two PbbHLH genes may be regulators of anthocyanin biosynthesis in P. bournei. Finally, overexpression of PbbHLH1 and PbbHLH2 in Nicotiana tabacum leaves triggered anthocyanin accumulation. These findings provide a basis for cultivating P. bournei varieties that have high ornamental value.

The advances in nanomedicine for bone and cartilage repair.

With the gradual demographic shift toward an aging and obese society, an increasing number of patients are suffering from bone and cartilage injuries. However, conventional therapies are hindered by the defects of materials, failing to adequately stimulate the necessary cellular response to promote sufficient cartilage regeneration, bone remodeling and osseointegration. In recent years, the rapid development of nanomedicine has initiated a revolution in orthopedics, especially in tissue engineering and regenerative medicine, due to their capacity to effectively stimulate cellular responses on a nanoscale with enhanced drug loading efficiency, targeted capability, increased mechanical properties and improved uptake rate, resulting in an improved therapeutic effect. Therefore, a comprehensive review of advancements in nanomedicine for bone and cartilage diseases is timely and beneficial. This review firstly summarized the wide range of existing nanotechnology applications in the medical field. The progressive development of nano delivery systems in nanomedicine, including nanoparticles and biomimetic techniques, which are lacking in the current literature, is further described. More importantly, we also highlighted the research advancements of nanomedicine in bone and cartilage repair using the latest preclinical and clinical examples, and further discussed the research directions of nano-therapies in future clinical practice.

Supratentorial pediatric cortical ependymomas: a comprehensive retrospective study.

Pediatric cortical ependymomas (CEs) are rare; the clinical features and optimal treatment remain ill-defined. We aimed to clarify the clinical characteristics and outcome of pediatric CEs based on institutional series and literature review. Thirteen children with CEs from our department were included in the present study. Furthermore, a search of English language peer-reviewed articles yielded 43 patients with CEs. The clinical data, treatment, and outcome were retrospectively reviewed and statistically analyzed. Our institutional series consisted of nine males and four females. The literature review yielded 56 pediatric CE cases (including ours) for further analysis. Of these 56 cases, frontal lobe (n = 19, 41.3%) was the most common location and most of the tumors were located in the right hemisphere (n = 27, 58.7%). Seizures (n = 23, 41.1%) were the most frequent preoperative symptoms. Thirty patients (n = 30, 53.6%) were WHO grade II. Five continuous patients in our series screened for C11orf95-RELA fusion and all the patients (100%) were RELA fusion positive. Fourteen (26.4%) patients experienced tumor recurrence and 4 (7.5%) patients died during the follow-up. Multivariate survival analysis depicted extent of surgery resection was the only prognostic factor for PFS and patient with gross total resection (P = 0.037, HR 3.682, 95% CI 1.082-13.79) had longer PFS. Furthermore, Log-rank testing for Kaplan-Meier survival analysis showed the extent of surgery resection (P = 0.007) was the only prognostic factor for OS. Pediatric CEs are rare, commonly seen in frontal lobe and right hemisphere. Seizures are the most common symptoms. They may have higher rate of RELA fusions, but favorable outcome. A low incidence of anaplastic histology has been depicted. Gross total resection is significantly associated with longer PFS and OS. Careful follow-up is necessary because the tumors may progress.

Primary cerebellar glioblastomas in children: clinical presentation and management.

Pediatric cerebellar glioblastomas (pcGBMs) are rare and their characteristics remain ill-defined. We conducted a retrospective analysis of pediatric cerebellar glioblastomas who underwent surgery from 2008 to 2019 in our department. Besides, we performed a literature review of the literature data on pcGBMs. Ten children with mean age of 9.4 years were included. During the follow-up, six patients died with mean survival time of 11.7 months, four patients survived with mean follow-up of 28 months. Seven patients underwent molecular analysis, no patients detected IDH1 mutations, four patients (57.1%) had H3K27M mutations, and two patients (28.6%) had MGMT promoter methylation. The literature review identified 38 pcGBMs cases (including ours), with mean age of 8.84 ± 4.20 years (range, 1-16 years). Increased ICP was the commonest sign. Eighteen (47.4%) patients underwent GTR and fifteen (45.5%) patients received STR. Postoperative radiation (RT) was conducted in 28 patients (75.7%) and 23 patients (65.7%) received chemotherapy. During the follow-up, 25 patients died with mean survival time of 12.21 months and 11 patients survived with average follow-up of 29.3 months. Kaplan-Meier survival depicted chemotherapy (P < 0.001) or radiation (P < 0.001) had positive impact on overall survival. Multivariate analysis revealed chemotherapy was a significant predictor of survival with a hazard ratio of 3.264 (P = 0.038). Our study found mean overall survival time for pcGBMs patients was 12.21 months. PcGBMs may have distinct molecular features, with higher incidence of H3K27M mutation and were always IDH1 wild-type. We recommend the routine postoperative radiotherapy and chemotherapy in pcGBMs.

[Research Progress in Promotion of Tissue Regeneration and Reconstruction with Exosomes Derived from Mesenchymal Stem Cells].

In regenerative medicine, stem cell therapy is an effective strategy for tissue regeneration and has a positive therapeutic effect on the regeneration and repair of defective tissues. In recent years, a series of studies have shown that the positive effects of stem cell therapy are mediated by exosomes released by the paracrine action of mesenchymal stem cells. Researchers have thus proposed a novel treatment strategy to use stem-cell-derived exosomes alone for tissue regeneration and repair, and affirmed through studies that the effects achieved were comparable to those of stem-cell-based therapies. Therefore, as a promising treatment strategy, exosome-based tissue regeneration treatment measures have been extensively studied. In this review, we discussed the latest knowledge of exosomes and the research progress in the regeneration and repair of related connective tissues, including the regeneration of bones, cartilage, skin, spinal cord and tendons, and briefly discussed the corresponding mechanisms. In addition, the challenges and prospects of tissue regeneration and repair based on mesenchymal stem cell exosomes were discussed.

GDF11 contributes to hepatic hepcidin (HAMP) inhibition through SMURF1-mediated BMP-SMAD signalling suppression.

Hepcidin (HAMP) synthesis is suppressed by erythropoiesis to increase iron availability for red blood cell production. This effect is thought to result from factors secreted by erythroid precursors. Growth differentiation factor 11 (GDF11) expression was recently shown to increase in erythroid cells of ß-thalassaemia, and decrease with improvement in anaemia. Whether GDF11 regulates hepatic HAMP production has never been experimentally studied. Here, we explore GDF11 function during erythropoiesis-triggered HAMP suppression. Our results confirm that exogenous erythropoietin significantly increases Gdf11 as well as Erfe (erythroferrone) expression, and Gdf11 is also increased, albeit at a lower degree than Erfe, in phlebotomized wild type and ß-thalassaemic mice. GDF11 is expressed predominantly in erythroid burst forming unit- and erythroid colony-forming unit- cells during erythropoiesis. Exogeneous GDF11 administration results in HAMP suppression in vivo and in vitro. Furthermore, exogenous GDF11 decreases BMP-SMAD signalling, enhances SMAD ubiquitin regulatory factor 1 (SMURF1) expression and induces ERK1/2 (MAPK3/1) signalling. ERK1/2 signalling activation is required for GDF11 or SMURF1-mediated suppression in BMP-SMAD signalling and HAMP expression. This research newly characterizes GDF11 in erythropoiesis-mediated HAMP suppression, in addition to ERFE.

BKCa compensates impaired coronary vasoreactivity through RhoA/ROCK pathway in hind-limb unweighted rats.

Previous studies have demonstrated cardiac and vascular remodeling induced by microgravity exposure. Yet, as the most important branch of vasculatures circulating the heart, the coronary artery has been seldomly studied about its adaptations under microgravity conditions. Large-conductance Ca2+-activated potassium channel (BKCa) and the Ras homolog family member A (RhoA)/Rho kinase (ROCK) pathway play key roles in control of vascular tone and mediation of microgravity-induced vascular adjustments. Therefore, we investigated the adaptation of coronary vasoreactivity to simulated microgravity and the role of BKCa and the RhoA/ROCK pathway in it. Four-week-old hind-limb unweighted (HU) rats were adopted to simulate effects of microgravity. Right coronary artery (RCA) constriction was measured by isometric force recording. The activity and expression of BKCa and the RhoA/ROCK pathway were examined by Western blot, patch-clamp recordings, and immunoprecipitation. We found HU significantly decreased RCA vasoconstriction to KCl, serotonin, and U-46619, but increased protein expression and current densities of BKCa, inhibition of which by iberiotoxin (IBTX) further decreased RCA vasoconstriction (P < 0.05). Expression of RhoA and ROCK as well as active RhoA and phosphorylation of myosin light chain (MLC) at Ser19 and MLC phosphatase target-1 at Thr696 were significantly increased by HU, and ROCK inhibitor Y-27632 exerted greater suppressing effect on HU RCA vasoconstriction than that of control (P < 0.05). BKCa opener NS1619 increased HU RCA vasoconstriction, which was blocked by both RhoA and ROCK inhibitor, similar to the effect of IBTX. These results indicate that HU impairs coronary vasoconstriction but enhances BKCa activity acting as a protective mechanism avoiding excessive decrease of coronary vasoreactivity through activation of the RhoA/ROCK pathway.-Wu, Y., Yue, Z., Wang, Q., Lv, Q., Liu, H., Bai, Y., Li, S., Xie, M., Bao, J., Ma, J., Zhu, X., Wang, Z. BKCa compensates impaired coronary vasoreactivity through RhoA/ROCK pathway in hind-limb unweighted rats.

A Retrospective Study from 2 Centers in China on the Effects of Continued Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers in Patients with Hypertension and COVID-19.

BACKGROUND Use of renin-angiotensin-aldosterone system inhibitors in coronavirus disease 2019 (COVID-19) patients lacks evidence and is still controversial. This study was designed to investigate effects of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) on clinical outcomes of COVID-19 patients and to assess the safety of ACEIs/ARBs medication. MATERIAL AND METHODS COVID-19 patients with hypertension from 2 hospitals in Wuhan, China, from 17 Feb to 18 Mar 2020 were retrospectively screened and grouped according to in-hospital medication. We performed 1: 1 propensity score matching (PSM) analysis to adjust for confounding factors. RESULTS We included 210 patients and allocated them to ACEIs/ARBs (n=81; 46.91% males) or non-ACEIs/ARBs (n=129; 48.06% males) groups. The median age was 68 [interquartile range (IQR) 61.5-76] and 66 (IQR 59-72.5) years, respectively. General comparison showed mortality in the ACEIs/ARBs group was higher (8.64% vs. 3.88%) but the difference was not significant (P=0.148). ACEIs/ARBs was associated with significantly more cases 7-categorical ordinal scale >2 at discharge, more cases requiring Intensive Care Unit (ICU) stay, and increased values and ratio of days that blood pressure (BP) was above normal range (P<0.05). PSM analysis showed no significant difference in mortality, cumulative survival rate, or other clinical outcomes such as length of in-hospital/ICU stay, BP fluctuations, or ratio of adverse events between groups after adjustment for confounding parameters on admission. CONCLUSIONS We found no association between ACEIs/ARBs and clinical outcomes or adverse events, thus indicating no evidence for discontinuing use of ACEIs/ARBs in the COVID-19 pandemic.

Prediction of endoscopic third ventriculostomy (ETV) success with preoperative third ventricle floor bowing (TVFB): a supplement to ETV success score.

Preoperative judgement of which children is likely to benefit from endoscopic third ventriculostomy (ETV) is still the most difficult challenge. This study aimed to compare the efficiency of third ventricular floor bowing (TVFB) and ETV success score (ETVSS) in selecting ETV candidates and achieve a better preoperative patient selection method for ETV based on our institutional experience. Children (≤ 16 years old) with newly diagnosed hydrocephalus treated with ETV between January 2013 and June 2018 were included in this prospective study. Patients with TVFB will receive ETV procedure in the pediatric subgroup of our department. ETVSS was calculated in every patient. The ETVSS predicted ETV success rate and the actual ETV success rate in our institution were compared and further analyzed. One hundred twenty-nine children with TVFB were enrolled in our study. The mean age at ETV was 5.84 ± 5.17 years (range, 0.04-16). Brain tumors, aqueductal stenosis, and inflammatory are the most common hydrocephalus etiologies. The most common complication was noninfectious fever (3.1%). During the average follow-up of 19.5 ± 14.95 months, twenty-five patients had depicted ETV failure. The actual ETV success rate (81%) in our study was higher than the success rate (69%) predicted by ETVSS. TVFB is a pragmatic, efficient, and simple model to predict the ETV outcome. We suggest that for hydrocephalic patients with preoperative third ventricular floor bowing, ETV should be the first-treatment choice regardless of the ETV success score. And for patients without such sign, ETVSS should be applied to select ETV candidates.

Third ventricle floor bowing: a useful measurement to predict endoscopic third ventriculostomy success in infantile hydrocephalus.

BACKGROUND: Preoperative judgment who will benefit from endoscopic third ventriculostomy (ETV) in infantile hydrocephalus remains controversial and no sufficient clue exists. Although ETV success score (ETVSS) is a useful scale in predicting ETV success in hydrocephalus, its efficacy in infants younger than 1 year old has been limited. This study aimed to verify the efficacy of a newly defined sign, "third ventricle floor bowing (TVFB)," in predicting ETV success in infantile hydrocephalus for the first time and discuss the mechanism of this sign and its clinical meanings. METHODS: Between January 2013 and April 2018, hydrocephalic infants (age ≤ 12 months) with third ventricle floor bowing were treated endoscopically in the Department of Neurosurgery, West China Hospital. The medical records of these patients were reviewed. Additionally, we undertook a detailed review of the reported data on the treatment of infantile hydrocephalus with endoscopic third ventriculostomy (ETV). RESULTS: A total of 42 infants underwent ETV alone in our institution, with a median age of 7.3 ± 3.8 months. Common etiologies included postinfectious (26.2%), arachnoid cyst (14.3%), aqueductal stenosis (11.9%), and congenital condition (11.9%). The complications included seizure (2.4%), CSF leak (2.4%), and subdural effusion (2.4%). During the average follow-up of 21.7 ± 13.1 months, the ETV success rate predicted by third ventricle floor bowing (TVFB) was 71.4%, which was higher than 6-month success rate predicted by the ETVSS (52.3%). However, it was difficult to reach statistical significance (P = 0.072) due to the limited sample size and further studies with larger sample size were needed. CONCLUSIONS: Our study suggests TVFB can serve as a useful method for selecting ETV candidates in infantile hydrocephalus preoperatively. And we speculate that good ventricle compliance and pressure difference between the ventricle and subarachnoid space are essential elements in ensuring ETV success.

Simultaneous transcatheter therapy for perimembranous ventricular septal defect combined with patent ductus arteriosus.

OBJECTIVE: This study aims to assess the clinical efficiency and safety of simultaneous transcatheter interventional treatment for perimembranous ventricular septal defect (pmVSD) combined with patent ductus arteriosus (PDA). METHODS: Twenty-five patients with pmVSD and PDA treated with simultaneous transcatheter interventions from April 2004 to December 2015 were included in this study. The mean age was 9.80 ± 8.14 years and the mean weight was 29.76 ± 14.82 Kg. Transthoracic echocardiography (TTE) and angiography were performed immediately after the procedure. Patients were re-examined by electrocardiogram, X-ray, and TTE at 2 days, 1 month, 3 months, and 6 months postoperatively. RESULTS: The interventional procedure was successfully performed in all 25 patients. No intraoperative complication was noted. TTE examination of the VSD and PDA immediately after the procedure showed no residual shunt and the occluder was well positioned. Among these patients, four patients showed electrocardiogram changes after the procedure that resolved after drug therapy. The cardiothoracic ratio, left atrial diameter, left ventricular end-systolic diameter, and left ventricular end-diastolic diameter recovered to normal in most patients at 6 months postoperatively. CONCLUSIONS: Simultaneously transcatheter interventional therapy is a safe and effective method for pmVSD combined with PDA.

Acute effects of Rho-kinase inhibitor fasudil on pulmonary arterial hypertension in patients with congenital heart defects.

BACKGROUND: We investigated the acute vasodilator effects of i.v. fasudil, a specific Rho-kinase inhibitor, on pulmonary circulation in patients with congenital heart defects (CHD) and severe pulmonary arterial hypertension (PAH). METHODS AND RESULTS: Thirty-five patients (34.23±12.10 years old) with CHD and severe PAH were consecutively enrolled. All patients underwent heart catheterization. At baseline and 30 min after initiation of i.v. fasudil, the following hemodynamic parameters were measured and calculated: right atrial pressure, pulmonary and systemic artery pressure (PAP and SAP), pulmonary and systemic vascular resistance, pulmonary-to-systemic blood pressure ratio (Pp/Ps), pulmonary-to-systemic blood flow ratio (Qp/Qs), cardiac index (CI) and artery oxygen saturation (SaO2). After fasudil treatment, marked decrease in mean PAP (mPAP), pulmonary vascular resistance (PVR), total pulmonary resistance, pulmonary-to-systemic vascular resistance ratio (Rp/Rs) and mean Pp/Ps (mPp/Ps) was found, while Qp/Qs increased significantly without affecting CI and SAP. mPAP, PVR, Rp/Rs and Qp/Qs tended to be improved more significantly in the post-tricuspid shunt group compared with the pre-tricuspid shunt group. CONCLUSIONS: Fasudil was well tolerated in patients with CHD and severe PAH, and significantly reduced PAP and PVR without affecting CI, SAP or SaO2.

The association between c.1333C > T genetic polymorphism of MTHFR gene and the risk of congenital heart diseases.

This study aims to evaluate the influence of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms on congenital heart diseases (CHD) risk. The frequencies of allelic and genotypic in CHD patients were significantly different from non-CHD controls. Our data suggested that the c.1333C > T genetic polymorphism of MTHFR gene was statistically associated with the increased risk of CHD [TT versus CC: odds ratio (OR) = 2.70, 95% confidence interval (CI) 1.34-5.45, p = 0.005; T versus C: OR = 1.38, 95% CI 1.03-1.86, p = 0.032]. Our findings indicate that the c.1333C > T genetic polymorphism influences CHD risk in the studied population.

Promotion of artery occlusion in dogs by percutaneous rotational atherectomy.

BACKGROUND: This study aims to offer experimental data and indirect evidences for the application of percutaneous rotational atherectomy to treat patent ductus arteriosus (PDA). METHODS: Eleven dogs (6 male dogs and 5 female dogs; aged 14-20 months, with an average of 16.7±3.2 months; weight 20-25 kg, with an average of 22.7±2.5 kg) were enrolled in this study. The diameters of the left and right arteries ranged from 3.2 to 4.8 mm (average 3.9±0.6 mm) on percutaneous angiography. Percutaneous rotational atherectomy with proper rotablator (the size was 1-1.5 mm larger than the artery diameter) was performed in the arterial intima. After 4 weeks from percutaneous rotational atherectomy, arteriography was conducted to observe the changes in artery diameter. Then all dogs were sacrificed and the pathologic examination was conducted on the left and right axillary arteries. RESULTS: There were obvious changes with different degrees in 22 arteries, including 8 arteries with complete occlusion and 12 arteries with stenosis (≥2/3, 1/2, and 1/3 stenosis in 4, 4, and 4 arteries, respectively). The occlusion rate was 36.4% and the total effective rate was 90.9%. It was considered failure in other 2 arteries with <1/3 of stenosis. CONCLUSIONS: Percutaneous rotational atherectomy of arterial intima can promote the occlusion of arteries. This has provided a new choice for the treatment of PDA.

Development of a multifunctional nano-hydroxyapatite platform (nHEA) for advanced treatment of severely infected full-thickness skin wounds.

The treatment of full-thickness skin injuries complicated by severe infection is hampered by the lack of comprehensive solutions that can regulate the various stages of wound healing. Consequently, there is an urgent need for a multifunctional dressing capable of multi-level regulation. In this study, we propose a novel solution by covalently integrating ε-poly-l-lysine-grafted gallic acid (EG) and in situ bioreduced silver nanoparticles (AgNPs) onto nano-hydroxyapatite (nHAP), thereby developing a multi-layered, multifunctional nanoplatform (nHEA). Cell experiments have shown that, compared to nHAP and nHAP loaded only with EG (nHEG), the addition of AgNPs to nHEA confers excellent antibacterial properties while maintaining optimal biocompatibility. The incorporation of EG onto nHEG and nHEA imparts antioxidation, anti-inflammatory, and pro-angiogenic functions, and the release of Ca2+ and EG further enhances fibroblast migration and collagen secretion. In a rat model of full-thickness skin injury with severe infection, nHEA demonstrates remarkable antibacterial and anti-inflammatory effects, along with promoting collagen remodeling and regeneration. Together, both cell experiments and animal studies confirm the significant potential of this innovative multifunctional nanoplatform in the treatment of full-thickness skin injuries with severe infection. STATEMENT OF SIGNIFICANCE: Treating infected full-thickness skin injuries poses a longstanding challenge due to the lack of comprehensive solutions that can regulate different stages of wound healing. This study introduces a novel multifunctional nanoplatform, nHEA, developed by covalently integrating ε-poly-l-lysine grafted with gallic acid (EG) and in situ bioreduced AgNPs onto nano-hydroxyapatite (nHAP). Cell experiments reveal that the integration of AgNPs enhances nHEA's antibacterial performance while maintaining optimal biocompatibility. The inclusion of EG bestows antioxidant, inflammation-regulating, and angiogenetic properties upon nHEA, and the release of Ca2+ and EG stimulates the migration and collagen secretion of fibroblast cells. Consequently, nHEA exhibits superior antibacterial and inflammation-regulating efficacy, and stimulates collagen remodeling and regeneration in vivo, making it a promising treatment for severely infected skin injuries.