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1.
J Mol Med (Berl) ; 102(5): 693-707, 2024 05.
Article in English | MEDLINE | ID: mdl-38492027

ABSTRACT

Physical therapy is extensively employed in clinical settings. Nevertheless, the absence of suitable animal models has resulted in an incomplete understanding of the in vivo mechanisms and cellular distribution that respond to physical stimuli. The objective of this research was to create a mouse model capable of indicating the cells affected by physical stimuli. In this study, we successfully established a mouse line based on the heat shock protein 70 (Hsp70) promoter, wherein the expression of CreERT2 can be induced by physical stimuli. Following stimulation of the mouse tail, ear, or cultured calvarias with heat shock (generated by heating, ultrasound, or laser), a distinct Cre-mediated excision was observed in cells stimulated by these physical factors with minimal occurrence of leaky reporter expression. The application of heat shock to Hsp70-CreERT2; FGFR2-P253R double transgenic mice or Hsp70-CreERT2 mice infected with AAV-BMP4 at calvarias induced the activation of Cre-dependent mutant FGFR2-P253R or BMP4 respectively, thereby facilitating the premature closure of cranial sutures or the repair of calvarial defects. This novel mouse line holds significant potential for investigating the underlying mechanisms of physical therapy, tissue repair and regeneration, lineage tracing, and targeted modulation of gene expression of cells in local tissue stimulated by physical factor at the interested time points. KEY MESSAGES: In the study, an Hsp70-CreERT2 transgenic mouse was generated for heat shock-induced gene modulation. Heat shock, ultrasound, and laser stimulation effectively activated Cre expression in Hsp70-CreERT2; reporter mice, which leads to deletion of floxed DNA sequence in the tail, ear, and cultured calvaria tissues of mice. Local laser stimuli on cultured calvarias effectively induce Fgfr2-P253R expression in Hsp70-mTmG-Fgfr2-P253R mice and result in accelerated premature closure of cranial suture. Heat shock activated AAV9-FLEX-BMP4 expression and subsequently promoted the repair of calvarial defect of Hsp70-CreERT2; Rosa26-mTmG mice.


Subject(s)
Bone Morphogenetic Protein 4 , HSP70 Heat-Shock Proteins , Mice, Transgenic , Promoter Regions, Genetic , Animals , HSP70 Heat-Shock Proteins/genetics , HSP70 Heat-Shock Proteins/metabolism , Mice , Bone Morphogenetic Protein 4/metabolism , Bone Morphogenetic Protein 4/genetics , Heat-Shock Response/genetics , Skull/metabolism , Gene Expression Regulation , Integrases/metabolism , Integrases/genetics
4.
J Int Med Res ; 52(1): 3000605231223441, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38258803

ABSTRACT

OBJECTIVE: To evaluate the safety and efficacy of bleomycin polidocanol foam (BPF) sclerotherapy for venous malformations (VMs) and analyze the associated clinical outcomes and predictors. METHODS: We retrospectively assessed BPF sclerotherapy outcomes in 138 patients with VMs. We analyzed pain levels, lesion volume reduction, and subjective perception of response. Logistic regression analysis was performed to identify potential predictors of treatment outcome. Additionally, we carefully monitored and recorded complications. RESULTS: There was a notable average reduction in lesion volume by 78.50% ± 15.71%. The pain numerical rating scale (NRS) score decreased from 4.17 ± 2.63 prior to treatment to 1.05 ± 1.54 afterward, and 70.3% of the patients experienced effective relief after a single BPF treatment. Multivariate analysis revealed that a high baseline NRS (odds ratio [OR]: 4.026) and elevated activated partial thromboplastin time (APTT, OR: 1.200) were positive predictors of pain reduction. Additionally, a high baseline NRS score (OR: 1.992) and elevated thrombocytocrit (PCT, OR: 2.543) were positive predictors of incomplete postoperative pain relief. Minor complications occurred in 31 (22.46%) patients. CONCLUSION: BPF sclerotherapy is safe and effective for VMs, resulting in significant reduction in lesion volume, improved symptoms, and minimal complications. APTT and PCT levels are important predictors of pain outcomes following BPF treatment.


Subject(s)
Bleomycin , Polyethylene Glycols , Sclerotherapy , Humans , Bleomycin/therapeutic use , Polidocanol , Retrospective Studies , Pain/etiology
5.
J Vasc Surg Venous Lymphat Disord ; 12(2): 101697, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37890588

ABSTRACT

OBJECTIVE: This study aims to investigate the difference in safety and efficacy between two treatments for venous malformations (VMs), electrochemotherapy combined with polidocanol foam (ECP) and bleomycin polidocanol foam (BPF), providing alternative therapies for VMs. METHODS: We conducted a retrospective review of 152 patients with VMs treated with ECP and BPF. Pre- and post-treatment magnetic resonance images (MRIs) were collected, and clinical follow-up assessments were performed. Imaging results were used to calculate lesion volume changes. Clinical outcomes included changes in pain and improvements in perceived swelling. Patients were followed up at 1 week and 6 months after surgery. All emerging complications were documented in detail. RESULTS: Of the 152 patients, 87 (57.2%) received BPF treatment, and 65 (42.8%) received ECP treatment. The most common location of VMs was the lower extremities (92/152; 60.2%), and the most common symptom was pain (108/152; 71.1%). Forty-three patients had previously undergone therapy in the BPF group (43/87; 49.4%), whereas 30 patients had received prior treatment in the ECP group (30/65; 46.2%). The study found that the percentage of lesion volume reduction in the BPF group was not significantly different from that in the ECP group (75.00% ± 17.85% vs 74.69% ± 8.48%; P = .899). ECP was more effective when the initial lesion volume was greater than 30 mL (67.66% ± 12.34% vs 73.47% ± 8.00%; P = .048). Patients treated with BPF had significantly less posttreatment pain than those treated with ECP, in different baseline lesion size. In the overall sample, pain relief was significantly higher in the BPF group than in the ECP group (4.21 ± 1.19 vs 3.57 ± 0.76; P = .002). However, there was no difference in pain relief between the two groups for the treatment of initially large VMs (4.20 ± 0.94 vs 3.70 ± 0.87; P = .113). The ECP group was significantly more likely to develop hyperpigmentation (5/87; 5.75% vs 11/65; 16.92%; P = .026) and swelling (9/87; 10.34% vs 16/65; 24.62%; P = .019) 1 week after surgery than the BPF group. CONCLUSIONS: Our study demonstrates that both BPF and ECP are effective treatments for VMs, with BPF being a safer option. ECP is a better choice for patients with the initial lesion volume greater than 30 mL, but it is more likely to lead to early swelling and hyperpigmentation.


Subject(s)
Electrochemotherapy , Hyperpigmentation , Polyethylene Glycols , Vascular Malformations , Humans , Polidocanol/adverse effects , Sclerosing Solutions , Bleomycin/adverse effects , Sclerotherapy/adverse effects , Sclerotherapy/methods , Electrochemotherapy/adverse effects , Vascular Malformations/diagnostic imaging , Vascular Malformations/therapy , Vascular Malformations/complications , Treatment Outcome , Pain/etiology , Retrospective Studies , Hyperpigmentation/etiology
6.
Signal Transduct Target Ther ; 8(1): 442, 2023 12 06.
Article in English | MEDLINE | ID: mdl-38057314

ABSTRACT

This prospective multicenter phase II study evaluated the clinical efficacy of neoadjuvant nivolumab-exclusive (N) and nivolumab-chemotherapy (N/C) combinations based on PD-L1 expression. Eligible patients exhibited resectable clinical stage IIA-IIIB (AJCC 8th edition) NSCLC without EGFR/ALK alterations. Patients received either mono-nivolumab (N) or nivolumab + nab-paclitaxel+ carboplatin (N/C) for three cycles based on PD-L1 expression. The primary endpoint was the major pathological response (MPR). Key secondary endpoints included the pathologic complete response (pCR), objective response rate (ORR), and event-free survival (EFS). Baseline PD-L1 expression and perioperative circulating tumor DNA (ctDNA) status were correlated with pCR and EFS. Fifty-two patients were enrolled, with 46 undergoing surgeries. The MPR was 50.0% (26/52), with 25.0% (13/52) achieving pCR, and 16.7% and 66.7% for patients with PD-L1 ≥ 50% in N and N/C groups, respectively. Thirteen (25.0%) patients experienced grade 3 or higher immune-related adverse events during neoadjuvant treatment. Patients with post-neoadjuvant ctDNA negativity was more likely to have pCR (39.1%) compared with those remained positive (6.7%, odds ratio = 6.14, 95% CI 0.84-Inf, p = 0.077). With a median follow-up of 25.1 months, the 18-month EFS rate was 64.8% (95% CI 51.9-81.0%). For patients with ctDNA- vs. ctDNA + , the 18m-EFS rate was 93.8% vs 47.3% (HR, 0.15; 95% CI 0.04, 0.94; p = 0.005). Immunochemotherapy may serve as an optimal neoadjuvant treatment even for patients with PD-L1 expression ≥ 50%. ctDNA negativity following neoadjuvant treatment and surgery could help identify superior pathological and survival benefits, which requires further confirmation in a prospective clinical trial (NCT04015778).


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Humans , Nivolumab/therapeutic use , Neoadjuvant Therapy/adverse effects , Platinum/therapeutic use , B7-H1 Antigen/genetics , Prospective Studies , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology
7.
Acta Pharm Sin B ; 13(1): 390-409, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36815041

ABSTRACT

Uncontrolled and persistent inflammation is closely related to numerous acute and chronic diseases. However, effective targeting delivery systems remain to be developed for precision therapy of inflammatory diseases. Herein we report a novel strategy for engineering inflammation-accumulation nanoparticles via phenolic functionalization. Different phenol-functionalized nanoparticles were first developed, which can undergo in situ aggregation upon triggering by the inflammatory/oxidative microenvironment. Phenolic compound-decorated poly (lactide-co-glycolide) nanoparticles, in particular tyramine (Tyr)-coated nanoparticles, showed significantly enhanced accumulation at inflammatory sites in mouse models of colitis, acute liver injury, and acute lung injury, mainly resulting from in situ cross-linking and tissue anchoring of nanoparticles triggered by local myeloperoxidase and reactive oxygen species. By combining a cyclodextrin-derived bioactive material with Tyr decoration, a multifunctional nanotherapy (TTN) was further developed, which displayed enhanced cellular uptake, anti-inflammatory activities, and inflammatory tissue accumulation, thereby affording amplified therapeutic effects in mice with colitis or acute liver injury. Moreover, TTN can serve as a bioactive and inflammation-targeting nanoplatform for site-specifically delivering a therapeutic peptide to the inflamed colon post oral administration, leading to considerably potentiated in vivo efficacies. Preliminary studies also revealed good safety of orally delivered TTN. Consequently, Tyr-based functionalization is promising for inflammation targeting amplification and therapeutic potentiation of nanotherapies.

8.
Thorac Cancer ; 14(5): 462-469, 2023 02.
Article in English | MEDLINE | ID: mdl-36511202

ABSTRACT

BACKGROUND: Anatomical variations often pose challenges to pulmonary surgery. Previous studies have mainly described the frequencies of bronchovascular anatomical variations in pulmonary segments, but did not determine the differences between pulmonary segments and the regularity behind these anatomical variations. Here, we attempted to investigate the regularity of bronchovascular anatomical variations in different pulmonary segments. METHODS: Thin-slice enhanced computed tomography data of 800 cases from our center were included in this study. Digitalized three-dimensional virtual lung segmentation was done, the dominant and inferior lung segments of the right upper lobe were defined, and the regularity of anatomical variations was explored. RESULTS: The mean volume ratio of the anterior segment of the right upper lobe (39.6 ± 8.6%) was highest, and that of the posterior segment (28.6 ± 7.9%) was lowest. Therefore, the dominant-type segment (DS + SDS) was dominant in the anterior segment, accounting for 74.6% (597/800), and the inferior-type segment (SIS + IS) was dominant in the posterior segment of the right upper lobe, accounting for 71.5% of cases (573/800). During the transformation of dominant and inferior lung segments, the corresponding regularity of anatomical variations could be displayed. For example, with an increase in the volume of the anterior segment of the right upper lobe, the occurrence rate of the bifurcated type of bronchus (B1 + 2, B3), the "central vein type" and the involvement of the trunk inferior and ascending artery in the blood supply of anterior segment gradually increased. CONCLUSIONS: The existence of dominant segments will increase the diversity of anatomical variations and the complexity of pulmonary segmentectomy.


Subject(s)
Pulmonary Surgical Procedures , Pulmonary Veins , Humans , Lung/surgery , Pulmonary Artery , Bronchi/diagnostic imaging
9.
J Vasc Surg Venous Lymphat Disord ; 11(1): 143-148, 2023 01.
Article in English | MEDLINE | ID: mdl-35940448

ABSTRACT

OBJECTIVE: The objective of this research was to retrospectively investigate the difference of safety and efficacy between polidocanol foam and bleomycin polidocanol foam (BPF) in the treatment of venous malformations (VMs), and provide clinical evidence for the application of BPF for VMs. METHODS: Patients with VMs treated with polidocanol foam and BPF were included between July 2018 and July 2020. The VM tissue involvements and symptoms were collected. The treatment outcomes were evaluated by the clinical improvement of symptoms and the degree of devascularization on ultrasound examination or magnetic resonance imaging. Patients were followed up for 1, 3, and 6 months after the sclerotherapy. Immediate and delayed complications were closely followed and recorded. RESULTS: A total of 51 patients were included, including 34 females and 17 males with a mean age of 26.8 years (range, 5-65 years). The most commonly involved sites were lower extremities (31/60 [51.7%]) and the most common symptom was pain (33/51 [64.7%]). Fifty-four sclerotherapies were performed with a mean of 1.06 ± 0.24 sessions (range, 1-2 sessions) per patient. The reduction percentage of lesion volume in the BPF group was significantly higher than the polidocanol foam group (79.4 ± 1.6% vs 55.7 ± 6.1%; P < .001). Patient satisfaction scores in the BPF group were significantly higher than the polidocanol foam group (7.2 ± 1.1 vs 5.7 ± 0.8; P < .001). No major complication was observed in either group. Cardiovascular and Interventional Radiological Society of Europe (CIRSE) grade 1 complications occurred in 5 of 21 patients in the BPF group and 7 of 30 patients in the polidocanol foam group, CIRSE grade 2 complications occurred in 5 of 21 patients in the BPF group and 4 of 30 patients in the polidocanol foam group; there were no significant differences between the two groups. CONCLUSIONS: BPF is a safe and effective sclerosant for VMs, showing better efficacy and similar safety as commonly used mild sclerosants. It could be a promising agent to treat VMs or other slow-flow vascular malformations.


Subject(s)
Bleomycin , Vascular Malformations , Male , Female , Humans , Adult , Polidocanol , Bleomycin/adverse effects , Retrospective Studies , Sclerosing Solutions , Sclerotherapy/adverse effects , Sclerotherapy/methods , Vascular Malformations/diagnostic imaging , Vascular Malformations/therapy , Treatment Outcome
10.
Int J Low Extrem Wounds ; 22(1): 168-173, 2023 Mar.
Article in English | MEDLINE | ID: mdl-33527869

ABSTRACT

Parkes-Weber syndrome (PWS) is a rare congenital vascular syndrome consisting of capillary, venous, lymphatic, and arteriovenous malformation. There are many complications of PWS, such as ulceration, bleeding, infection, and cardiac failure. Among them, skin ulceration is one of the thorniest problems in PWS, requiring multidisciplinary approaches for the management. In this article, we presented the case of an elderly patient with refractory ulceration who received numerous treatments with no effect and finally underwent a major amputation to improve the quality of life. Moreover, we reviewed 23 previously reported cases to improve our understanding of the management for PWS patients with ulceration.


Subject(s)
Arteriovenous Malformations , Klippel-Trenaunay-Weber Syndrome , Sturge-Weber Syndrome , Humans , Aged , Sturge-Weber Syndrome/complications , Sturge-Weber Syndrome/diagnosis , Sturge-Weber Syndrome/surgery , Quality of Life , Klippel-Trenaunay-Weber Syndrome/complications , Arteriovenous Malformations/complications , Arteriovenous Malformations/diagnosis , Arteriovenous Malformations/surgery , Amputation, Surgical
11.
Front Surg ; 9: 941582, 2022.
Article in English | MEDLINE | ID: mdl-36311929

ABSTRACT

Objective: Anatomical segmentectomy has been proven to be a viable surgical treatment for small-size peripheral lung nodules. Three-dimensional (3D) reconstruction computed tomography (CT) has been proposed as an effective approach to overcome the challenges of encountering pulmonary anatomical variations when performing segmentectomy. Therefore, to further investigate the usefulness of preoperative 3D reconstruction CT in segmentectomy, we will conduct this prospective, multicenter randomized controlled DRIVATS study to compare the use of 3D reconstruction CT with standard chest CT in video-assisted segmentectomy (ClinicalTrials.gov ID: NCT04004494). Methods: This study began in July 2019 and a total of 190 patients will be accrued from three clinical centers within 4 years. The main inclusion criteria are patients with a single peripheral nodule 0.8-2 cm with at least one of the following requirements: (i) histology of adenocarcinoma in situ; (ii) nodule has ≥50% ground-glass appearance on CT; (iii) radiologic surveillance confirms a long doubling time (≥400 days). Surgical procedures include segmental resection of the lesion and mediastinal lymph node sampling (subsegmental resection or combined subsegmental resection will not be included in this study). The primary endpoint is operative time. The secondary endpoints include incidence of change of surgical plan, intraoperative blood loss, conversion rate, operative accident event, incidence of postoperative complications, postoperative hospital stay, length of hospitalization, duration of chest tube placement, postoperative 30-day mortality, dissection of lymph nodes, overall survival, disease-free survival, preoperative lung function, and postoperative lung function. Discussion: This multicenter DRIVATS study aims to verify the usefulness of preoperative 3D reconstruction CT compared with standard chest CT in segmentectomy. If successfully completed, this multicenter prospective study will provide a higher level of evidence for the use of 3D reconstruction CT in segmentectomy.

12.
Front Oncol ; 12: 1002953, 2022.
Article in English | MEDLINE | ID: mdl-36313666

ABSTRACT

Background: Estimating the growth of pulmonary sub-solid nodules (SSNs) is crucial to the successful management of them during follow-up periods. The purpose of this study is to (1) investigate the measurement sensitivity of diameter, volume, and mass of SSNs for identifying growth and (2) seek to establish a deep learning-based model to predict the growth of SSNs. Methods: A total of 2,523 patients underwent at least 2-year examination records retrospectively collected with sub-solid nodules. A total of 2,358 patients with 3,120 SSNs from the NLST dataset were randomly divided into training and validation sets. Patients from the Yibicom Health Management Center and Guangdong Provincial People's Hospital were collected as an external test set (165 patients with 213 SSN). Trained models based on LUNA16 and Lndb19 datasets were employed to automatically obtain the diameter, volume, and mass of SSNs. Then, the increase rate in measurements between cancer and non-cancer groups was studied to evaluate the most appropriate way to identify growth-associated lung cancer. Further, according to the selected measurement, all SSNs were classified into two groups: growth and non-growth. Based on the data, the deep learning-based model (SiamModel) and radiomics model were developed and verified. Results: The double time of diameter, volume, and mass were 711 vs. 963 days (P = 0.20), 552 vs. 621 days (P = 0.04) and 488 vs. 623 days (P< 0.001) in the cancer and non-cancer groups, respectively. Our proposed SiamModel performed better than the radiomics model in both the NLST validation set and external test set, with an AUC of 0.858 (95% CI 0.786-0.921) and 0.760 (95% CI 0.646-0.857) in the validation set and 0.862 (95% CI 0.789-0.927) and 0.681 (95% CI 0.506-0.841) in the external test set, respectively. Furthermore, our SiamModel could use the data from first-time CT to predict the growth of SSNs, with an AUC of 0.855 (95% CI 0.793-0.908) in the NLST validation set and 0.821 (95% CI 0.725-0.904) in the external test set. Conclusion: Mass increase rate can reflect more sensitively the growth of SSNs associated with lung cancer than diameter and volume increase rates. A deep learning-based model has a great potential to predict the growth of SSNs.

13.
Thorac Cancer ; 13(15): 2210-2222, 2022 08.
Article in English | MEDLINE | ID: mdl-35818719

ABSTRACT

OBJECTIVE: In recent years, the lung cancer incidence has grown and the population is younger. We intend to find out the true detection rate of pulmonary nodules and the incidence of lung cancer in the population and search for the risk factors. METHOD: Hospital employees ≥40 years old who underwent low-dose computed tomography (CT) lung cancer screening from January 2019 to March 2022 were selected to record CT-imaging characteristics, pathology, staging, and questionnaires to investigate past history, smoking history, diet, mental health, etc. PM2.5 and radiation intake in radiation-related occupation received monitoring in hospital. RESULT: The detection rate of suspicious pulmonary nodules was 9.1% (233/2552), and the incidence rate of lung cancer (including adenocarcinoma in situ) was 4.0% (103/2552). Morbidity among doctors, nurses, technicians, administers, and logistics was no difference (p = 0.184), but higher in women than in men (4.7% vs 2.4% p = 0.002). The invasiveness increased with age and CT density of nodules (p = 0.018). The relationship between lung cancer morbidity and PM2.5 was not clear (p = 0.543); and no lung cancer has been found in employees related ionizing radiation. CONCLUSION: The high screening rate has brought about a high incidence of lung cancer. At present, the risk factor analysis of lung cancer based on small samples cannot find the direct cause. Most of the ground glass opacity (GGO)s detected by LDCT screening are indolent, but there are also rapidly progressive lung cancer. A predictive model to identify active and indolent GGO is necessary.


Subject(s)
Lung Neoplasms , Multiple Pulmonary Nodules , Adult , China/epidemiology , Early Detection of Cancer/methods , Female , Hospitals , Humans , Incidence , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/epidemiology , Lung Neoplasms/etiology , Male , Risk Factors
14.
Cancer Discov ; 12(7): 1690-1701, 2022 07 06.
Article in English | MEDLINE | ID: mdl-35543554

ABSTRACT

The efficacy and potential limitations of molecular residual disease (MRD) detection urgently need to be fully elucidated in a larger population of non-small cell lung cancer (NSCLC). We enrolled 261 patients with stages I to III NSCLC who underwent definitive surgery, and 913 peripheral blood samples were successfully detected by MRD assay. Within the population, only six patients (3.2%) with longitudinal undetectable MRD recurred, resulting in a negative predictive value of 96.8%. Longitudinal undetectable MRD may define the patients who were cured. The peak risk of developing detectable MRD was approximately 18 months after landmark detection. Correspondingly, the positive predictive value of longitudinal detectable MRD was 89.1%, with a median lead time of 3.4 months. However, brain-only recurrence was less commonly detected by MRD (n = 1/5, 20%). Further subgroup analyses revealed that patients with undetectable MRD might not benefit from adjuvant therapy. Together, these results expound the value of MRD in NSCLC. SIGNIFICANCE: This study confirms the prognostic value of MRD detection in patients with NSCLC after definitive surgery, especially in those with longitudinal undetectable MRD, which might represent the potentially cured population regardless of stage and adjuvant therapy. Moreover, the risk of developing detectable MRD decreased stepwise after 18 months since landmark detection. This article is highlighted in the In This Issue feature, p. 1599.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/surgery , Humans , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , Lung Neoplasms/surgery , Neoplasm, Residual/diagnosis , Prognosis
15.
Inflamm Res ; 71(2): 243-253, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35059772

ABSTRACT

OBJECTIVE: Inflammation and proliferation of vascular smooth muscle cells (VSMCs), induced by angiotensin II (AngII) and other growth factors, play important roles in the pathogenesis of hypertension, restenosis, and atherosclerosis. Dihydroartemisinin (DHA) exhibits broad protective effects. However, the effects of DHA on AngII-induced inflammation and proliferation of VSMCs remain unknown. MATERIALS AND METHODS: AngII was used to construct VSMCs and vascular inflammation model in vitro and in vivo. The protective roles of DHA in inflammatory response and proliferation were evaluated through CCK-8, BrdU assay and immunofluorescence staining. The level of mRNA N6-methyladenosine was measured by m6A-RNA immunoprecipitation (MeRIP) assay. Western blot and quantitative real-time PCR were used to investigate the relationship between FTO and its potential downstream signaling molecules. RESULTS: In the present study, we found that DHA significantly suppressed AngII-induced proliferation of VSMCs and the expression of IL-6 and Ccl2 in a dose-dependent manner. Additionally, we confirmed that fat mass and obesity-associated (FTO) plays a critical role in AngII-induced VSMC proliferation and inflammation. FTO knockdown increased the methylation level of NR4A3 mRNA, whereas FTO, but not mutated FTO overexpression, reduced the methylation level of NR4A3 mRNA. These results suggest that DHA plays a protective role in AngII-induced VSMC proliferation and the associated inflammation by inhibiting the FTO/NR4A3 axis. CONCLUSION: Our findings provide new insight into the mechanisms of DHA and its critical role in the pathogenesis of hypertension-related vascular complications.


Subject(s)
Alpha-Ketoglutarate-Dependent Dioxygenase FTO/antagonists & inhibitors , Angiotensin II/pharmacology , Artemisinins/pharmacology , DNA-Binding Proteins/antagonists & inhibitors , Inflammation/prevention & control , Muscle, Smooth, Vascular/drug effects , Myocytes, Smooth Muscle/drug effects , Nerve Tissue Proteins/antagonists & inhibitors , Receptors, Steroid/antagonists & inhibitors , Receptors, Thyroid Hormone/antagonists & inhibitors , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/physiology , Animals , Cell Proliferation/drug effects , Cells, Cultured , DNA-Binding Proteins/physiology , Mice , Muscle, Smooth, Vascular/cytology , Myocytes, Smooth Muscle/physiology , Nerve Tissue Proteins/physiology , Receptors, Steroid/physiology , Receptors, Thyroid Hormone/physiology , Signal Transduction/drug effects
16.
Vascular ; 30(2): 349-356, 2022 Apr.
Article in English | MEDLINE | ID: mdl-33878955

ABSTRACT

BACKGROUND: The endovascular technique of mechanochemical ablation (MOCA) has become popular in treating patients with saphenous reflux. We reported the histopathological findings in human ex-vivo incompetent great saphenous veins following treatment with saline, polidocanol, mechanical ablation and MOCA using ClariVein device. METHODS: Twenty-four vein GSV specimens were obtained via traditional surgery and treated with four methods: Group A: 0.9% normal saline (NS); Group B: 3% polidocanol; Group C: mechanical ablation + 0.9% NS; Group D: mechanical ablation + 3% polidocanol (MOCA). Hematoxylin and eosin (HE), Masson's trichrome and immunohistochemical staining were performed on each specimen and integrated optical densities were measured with vWF and a-SMA stains and statistically evaluated. vWF staining was used to assess endothelial damage and a a-SMA staining was used to assess media injury. RESULTS: HE and Masson's trichrome staining of Groups C and D revealed severe damage to the endothelium and media compared to Groups A and B. The statistical result of vWF staining showed the damage of endothelium was significantly increased by Group D compared to Groups A, B and C. The statistical result of a-SMA staining showed the damage of media was significantly increased by Groups C and D compared to Groups A and B. CONCLUSIONS: The mechanism of MOCA was caused by both endothelium damage and media tearing. The damage of endothelium was significantly increased by MOCA when compared with mechanical ablation alone.


Subject(s)
Ablation Techniques , Varicose Veins , Venous Insufficiency , Ablation Techniques/adverse effects , Humans , Polidocanol , Saphenous Vein/diagnostic imaging , Saphenous Vein/pathology , Saphenous Vein/surgery , Sclerotherapy/adverse effects , Treatment Outcome , Varicose Veins/diagnostic imaging , Varicose Veins/surgery , Venous Insufficiency/diagnostic imaging , Venous Insufficiency/surgery
18.
Medicine (Baltimore) ; 100(26): e26566, 2021 Jul 02.
Article in English | MEDLINE | ID: mdl-34190198

ABSTRACT

ABSTRACT: The aim of this study was to investigate the clinical effect of AO miniplate screw internal fixation and Kirschner wire (KW) in the treatment of metacarpal fractures.We retrospectively analyzed the clinical data of 590 metacarpal fracture patients admitted to our hospital from March 2016 to March 2019. Among them, 290 patients were treated with KWs; 300 were treated with AO microplate internal fixation. The clinical, radiological results, time of surgery, and complications were observed and compared between the 2 groups.The imaging characteristics and preoperative fracture types of the 2 groups were similar and comparable (P > .05). The operation time, length of hospital stay, and fracture healing time of AO group were shorter than those of KW group, and the differences were statistically significant (41.22 ±â€Š7.23 vs 25.64 ±â€Š6.29; 7.13 ±â€Š2.38 vs 5.26 ±â€Š1.71; 67.43 ±â€Š22.01 vs 52.57 ±â€Š17.46, P < .05). In addition, the incidence of postoperative complications in AO group was lower than that in KW group (8.3% vs 15.2%, P < .05). In terms of surgical knuckle extension, flexion, and total mobility (compared with the uninjured hand), patients in the AO plate group were significantly improved compared with patients in the KW group, and the difference was statistically significant (4 vs 10 degree; 19 vs 10 degree; 14 vs 29 degree, P < .05); The average degree of finger rotation deformity in AO plate group was significantly lower than that in KW group (1 vs 6 degree, P < .05). In terms of grip strength (compared with the healthy hand), the average grip strength of AO plate group was significantly higher than that of KW group (93% vs 83%, P < .05). Patients in the OA plate group had a lower Disabilities of the Arm, Shoulder and Hand score (P < .05).Compared with KW fixation, AO mini-plate and screw fixation for the metacarpal fracture has a better effect, which can effectively shorten the operation time and reduce the trauma to patients. It can provide patients with better stability and realize the early movement of the palm, promote fracture healing and joint function recovery; it can reduce the incidence of postoperative complications, which has certain safety. In addition, it can effectively reduce the risk of poor finger rotation.


Subject(s)
Bone Plates , Bone Wires , Finger Phalanges , Fracture Fixation, Intramedullary , Hand Deformities , Metacarpal Bones/injuries , Postoperative Complications , Adult , China/epidemiology , Disability Evaluation , Female , Finger Phalanges/injuries , Finger Phalanges/surgery , Fracture Fixation, Intramedullary/adverse effects , Fracture Fixation, Intramedullary/instrumentation , Fracture Fixation, Intramedullary/methods , Fracture Healing , Fractures, Bone/surgery , Hand Deformities/etiology , Hand Deformities/prevention & control , Hand Injuries/surgery , Humans , Male , Outcome Assessment, Health Care , Postoperative Complications/diagnosis , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Range of Motion, Articular , Recovery of Function
19.
ACS Appl Mater Interfaces ; 13(24): 28334-28347, 2021 Jun 23.
Article in English | MEDLINE | ID: mdl-34121403

ABSTRACT

The free-standing Ni-Al2O3 ensemble derived from NiAl-layered double hydroxides (NiAl-LDHs) grown onto a Ni-foam has been developed for the exothermic gas-phase acetone hydrogenation to isopropanol. This approach works effectively and efficiently to achieve a unique combination of high activity/selectivity and enhanced heat/mass transfer stemmed from the Ni-foam. The outstanding catalyst is obtained by direct reduction of the un-calcined NiAl-LDH/Ni-foam, with a high turnover frequency of 0.90 s-1, being capable of converting 90.8% acetone into isopropanol with almost 100% selectivity under stoichiometric H2/acetone molar ratio, atmospheric pressure at 80 °C, and a WHSVacetone of 10 h-1. The catalyst derivation using the un-calcined NiAl-LDH/Ni-foam enables the Ni nanoparticles to be intertwined with Al2O3 to form a large Ni-Al2O3 interface, without interruption of impurities such as irreducible NiO (in the case of calcined NiAl-LDH/Ni-foam samples), which markedly improves the strong acetone adsorption next to the Ni0 hydrogenation sites, thereby leading to a dramatic improvement of catalyst activity.

20.
Biomaterials ; 275: 120952, 2021 08.
Article in English | MEDLINE | ID: mdl-34147720

ABSTRACT

It remains a great challenge for targeted therapy of heart diseases. To achieve desirable heart targeting, we developed a polyphenol-assisted nanoprecipitation/self-assembly approach for facile engineering of functional nanoparticles. Three different materials were employed as representative carriers, while gallic acid, catechin, epigallocatechin gallate, and tannic acid (TA) served as typical polyphenols with varied numbers of phenolic hydroxyl groups. By optimizing different parameters, such as polyphenol types and the weight ratio of carrier materials and polyphenols, well-defined nanoparticles with excellent physicochemical properties can be easily prepared. Regardless of various carrier materials, TA-derived nanoparticles showed potent reactive oxygen species-scavenging activity, especially nanoparticles produced from a cyclodextrin-derived bioactive material (TPCD). By internalization into cardiomyocytes, TPCD/TA nanoparticles (defined as TPTN) effectively protected cells from hypoxic-ischemic injury. After intravenous injection, TPTN considerably accumulated in the injured heart in two murine models of ventricular fibrillation cardiac arrest in rats and myocardial hypertrophy in mice. Correspondingly, intravenously delivered TPTN afforded excellent therapeutic effects in both heart diseases. Preliminary experiments also revealed good safety of TPTN. These results substantiated that TPTN is a promising nanotherapy for targeted treatment of heart diseases, while polyphenol-assisted self-assembly is a facile but robust strategy to develop heart-targeting delivery systems.


Subject(s)
Heart Diseases , Nanoparticles , Animals , Mice , Polyphenols , Rats , Reactive Oxygen Species , Tannins
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