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1.
Proc Natl Acad Sci U S A ; 121(14): e2318391121, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38527207

ABSTRACT

The exploitation of novel wound healing methods with real-time infection sensing and high spatiotemporal precision is highly important for human health. Pt-based metal-organic cycles/cages (MOCs) have been employed as multifunctional antibacterial agents due to their superior Pt-related therapeutic efficiency, various functional subunits and specific geometries. However, how to rationally apply these nanoscale MOCs on the macroscale with controllable therapeutic output is still challenging. Here, a centimeter-scale Pt MOC film was constructed via multistage assembly and subsequently coated on a N,N'-dimethylated dipyridinium thiazolo[5,4-d]thiazole (MPT)-stained silk fabric to form a smart wound dressing for bacterial sensing and wound healing. The MPT on silk fabric could be used to monitor wound infection in real-time through the bacteria-mediated reduction of MPT to its radical form via a color change. The MPT radical also exhibited an excellent photothermal effect under 660 nm light irradiation, which could not only be applied for photothermal therapy but also induce the disassembly of the Pt MOC film suprastructure. The highly ordered Pt MOC film suprastructure exhibited high biosafety, while it also showed improved antibacterial efficiency after thermally induced disassembly. In vitro and in vivo studies revealed that the combination of the Pt MOC film and MPT-stained silk can provide real-time information on wound infection for timely treatment through noninvasive techniques. This study paves the way for bacterial sensing and wound healing with centimeter-scale metal-organic materials.


Subject(s)
Platinum , Wound Infection , Humans , Platinum/pharmacology , Wound Healing , Bandages , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Silk/chemistry , Bacteria , Hydrogels/pharmacology
2.
FASEB J ; 38(3): e23452, 2024 02 15.
Article in English | MEDLINE | ID: mdl-38308640

ABSTRACT

Autophagy is implicated in the pathogenesis of pulmonary arterial hypertension (PAH). We aimed to investigate whether the p62-Keap1-Nrf2 pathway affects the development of PAH by mediating autophagy. A PAH rat model was established using monocrotaline (MCT). Pulmonary artery smooth muscle cells (PASMCs) were extracted, and the changes in proliferation, migration, autophagy, and oxidative stress were analyzed following overexpression or knockdown of p62. The impact of p62 on the symptoms of PAH rats was assessed by the injection of an adenovirus overexpressing p62. We found that the knockdown of p62 increased the proliferation and migration of PASMCs, elevating the oxidative stress of PASMCs and upregulating gene expression of NADPH oxidases. Co-IP assay results demonstrated that p62 interacted with Keap1. p62 knockdown enhanced Keap1 protein stability and Nrf2 ubiquitination. LC3II/I and ATG5 were expressed more often when p62 was knocked down. Treating with an inhibitor of autophagy reversed the impact of p62 knockdown on PASMCs. Nrf2 inhibitor treatment reduced the expression of Nrf2 and p62, while increasing the expression of Keap1, LC3II/I, and ATG5 in PASMCs. However, overexpressing p62 diminished mRVP, SPAP, and Fulton index in PAH rats and attenuated pulmonary vascular wall thickening. Overexpression of p62 also decreased the expression of Keap1, LC3II/I, and ATG5 and increased the nuclear expression of Nrf2 in PAH rats. Importantly, overexpression of p62 reduced oxidative stress and the NADPH oxidase expression in PAH rats. Overall, activation of the p62-Keap1-Nrf2 positive feedback signaling axis reduces the proliferation and migration of PASMCs and alleviates PAH by inhibiting autophagy and oxidative stress.


Subject(s)
Pulmonary Arterial Hypertension , Animals , Rats , Autophagy/physiology , Cell Proliferation , Kelch-Like ECH-Associated Protein 1/genetics , Kelch-Like ECH-Associated Protein 1/metabolism , Monocrotaline , Myocytes, Smooth Muscle/metabolism , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Pulmonary Arterial Hypertension/pathology , Pulmonary Artery/metabolism
3.
Genomics ; 116(5): 110889, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38901654

ABSTRACT

Cholangiocarcinoma (CCA) is widely noted for its high degree of malignancy, rapid progression, and limited therapeutic options. This study was carried out on transcriptome data of 417 CCA samples from different anatomical locations. The effects of lipid metabolism related genes and immune related genes as CCA classifiers were compared. Key genes were derived from MVI subtypes and better molecular subtypes. Pathways such as epithelial mesenchymal transition (EMT) and cell cycle were significantly activated in MVI-positive group. CCA patients were classified into three (four) subtypes based on lipid metabolism (immune) related genes, with better prognosis observed in lipid metabolism-C1, immune-C2, and immune-C4. IPTW analysis found that the prognosis of lipid metabolism-C1 was significantly better than that of lipid metabolism-C2 + C3 before and after correction. KRT16 was finally selected as the key gene. And knockdown of KRT16 inhibited proliferation, migration and invasion of CCA cells.

4.
Nano Lett ; 24(15): 4649-4657, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38572971

ABSTRACT

Deep-seated bacterial infections (DBIs) are stubborn and deeply penetrate tissues. Eliminating deep-seated bacteria and promoting tissue regeneration remain great challenges. Here, a novel radical-containing hydrogel (SFT-B Gel) cross-linked by a chaotropic effect was designed for the sensing of DBIs and near-infrared photothermal therapy (NIR-II PTT). A silk fibroin solution stained with 4,4',4″-(1,3,5-triazine-2,4,6-triyl)tris(1-methylpyridin-1-ium) (TPT3+) was employed as the backbone, which could be cross-linked by a closo-dodecaborate cluster (B12H122-) through a chaotropic effect to form the SFT-B Gel. More interestingly, the SFT-B Gel exhibited the ability to sense DBIs, which could generate a TPT2+• radical with obvious color changes in the presence of bacteria. The radical-containing SFT-B Gel (SFT-B★ Gel) possessed strong NIR-II absorption and a remarkable photothermal effect, thus demonstrating excellent NIR-II PTT antibacterial activity for the treatment of DBIs. This work provides a new approach for the construction of intelligent hydrogels with unique properties using a chaotropic effect.


Subject(s)
Phototherapy , Photothermal Therapy , Hydrogels/pharmacology
5.
Acta Pharmacol Sin ; 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39043968

ABSTRACT

Small cell lung cancer (SCLC) is a recalcitrant malignancy with dismal prognosis due to rapid relapse after an initial treatment response. More effective treatments for SCLC are desperately needed. Our previous studies showed that cell migration-inducing hyaluronan binding protein (CEMIP) functionally promotes SCLC cell proliferation and metastasis. In this study, we investigated whether and how CEMIP regulates the chemosensitivity of SCLC. Through the GDSC database, we found that CEMIP expression levels were positively correlated with the IC50 values of several commonly used chemotherapeutic drugs in SCLC cells (cisplatin, gemcitabine, 5-fluorouracil and cyclophosphamide). We demonstrated that overexpression or knockdown of CEMIP in SCLC cells resulted in a notable increase or reduction in the IC50 value of cisplatin or etoposide, respectively. We further revealed that CEMIP functions as an adaptor protein in SCLC cells to interact with SRC and YAP through the 1-177 aa domain and 820-1361 aa domain, respectively, allowing the autophosphorylation of Y416 and activation of SRC, thus facilitating the interaction between YAP and activated SRC, and resulting in increased phosphorylation of Y357, protein stability, nuclear accumulation and transcriptional activation of YAP. Overexpressing SRC or YAP counteracted the CEMIP knockdown-mediated increase in the sensitivity of SCLC cells to cisplatin and etoposide. The combination of the SRC inhibitor dasatinib or the YAP inhibitor verteporfin and cisplatin/etoposide (EP regimen) displayed excellent synergistic antitumor effects on SCLC both in vitro and in vivo. This study demonstrated that targeted therapy against the CEMIP/SRC/YAP complex is a potential strategy for SCLC and provides a rationale for the development of future clinical trials with translational prospects.

6.
Support Care Cancer ; 32(5): 284, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38607445

ABSTRACT

OBJECTIVE: This longitudinal study aims to examine the present state of perceived control, self-management efficacy, and overall quality of life (QoL) in patients with breast cancer undergoing radiotherapy, and gain insight into the dynamic trends and factors that influence the quality of life experienced by patients during the course of radiotherapy. METHODS: Participants completed the Cancer Experience and Efficacy Scale (CEES), Strategies Used by People to Promote Health (SUPPH), and Functional Assessment of Cancer Therapy- Breast (FACT-B). The data was analyzed using the software SPSS26.0. Repeated measures analysis of variance (ANOVA) and mixed-effects linear models were used to analyze trends in perceived control, self-management efficacy, and QoL at three-time points, as well as factors affecting QoL during radiotherapy. RESULTS: Perceived control and self-management efficacy were associated with QoL over the course of the radiotherapy. Self-management efficacy (ß = 0.30, P < 0.001), presence of chemotherapy (ß = 18.33, P = 0.024), and duration of illness (ß = 2.25, P = 0.028) had a positive effect on the change in QoL, while time (ß = - 2.95, P < 0.001), cancer experience (ß = - 0.46, P < 0.001), and type of medical insurance (ß = - 2.77, P = 0.021) had the negative effect on the change in QoL. CONCLUSION: The QoL, perceived control, and self-efficacy of patients with breast cancer show dynamic changes during radiotherapy. The higher the self-efficacy, the better the QoL, and the worse the QoL when the sense of disease control is poor. At the same time, more attention should be paid to the QoL of breast cancer radiotherapy patients with a long course of the disease, receiving chemotherapy, and different medical payment methods.


Subject(s)
Breast Neoplasms , Self-Management , Humans , Female , Breast Neoplasms/radiotherapy , Quality of Life , Longitudinal Studies , Health Promotion , Self Efficacy
7.
Surg Endosc ; 38(8): 4422-4430, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38898340

ABSTRACT

BACKGROUND: Endoscopic ultrasound-guided pancreatic duct (PD) drainage (EUS-PDD) is being increasingly performed as an alternative method to surgical drainage to achieve PD decompression after failed endoscopic retrograde pancreatography (ERP). However, no directly study has compared EUS-PDD with surgical PD drainage after failed ERP in patients with chronic pancreatitis. METHODS: Consecutive patients who underwent EUS-PDD or longitudinal pancreaticojejunostomy after failed ERP were retrospectively identified from our endoscopy and medical information systems. The primary end point was the Izbicki pain score. The secondary end points were pain relief at the end of follow-up, procedure outcomes, adverse events, readmission, and reintervention. RESULTS: A total of 21 patients (11 EUS-PDD, 10 surgical drainages) were analyzed. There were no significant differences in mean Izbicki pain score (EUS-PDD, 13.6 ± 10.1 vs. surgical drainage 10.7 ± 7.9, p = 0.483) or complete/partial pain relief (60%/30% vs. 70%/30%, p = 0.752) at the end of follow-up of the two groups. The rates of overall adverse events (27.3% vs. 30.0%, p = 0.893) and readmission (63.6% vs. 40.0%, p = 0.290) were similar in the two treatment groups, while patients in EUS-PDD group required more reinterventions (45.5% vs. 0%, p = 0.039) compared with patients in the surgery group. CONCLUSION: EUS-PDD showed comparable pain relief and safety to surgical PD drainage after failed ERP, with a higher rate of reintervention. The selection of EUS-PDD or surgical drainage may be appropriate based on an individualized strategy.


Subject(s)
Cholangiopancreatography, Endoscopic Retrograde , Drainage , Endosonography , Pancreatic Ducts , Pancreatitis, Chronic , Humans , Drainage/methods , Male , Female , Middle Aged , Retrospective Studies , Pilot Projects , Pancreatic Ducts/surgery , Pancreatic Ducts/diagnostic imaging , Pancreatitis, Chronic/surgery , Pancreatitis, Chronic/diagnostic imaging , Cholangiopancreatography, Endoscopic Retrograde/methods , Endosonography/methods , Adult , Ultrasonography, Interventional/methods , Treatment Failure , Aged , Treatment Outcome
8.
Cell Mol Biol Lett ; 29(1): 58, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38649803

ABSTRACT

Non-small cell lung cancer (NSCLC), characterized by low survival rates and a high recurrence rate, is a major cause of cancer-related mortality. Aberrant activation of the PI3K/AKT/mTOR signaling pathway is a common driver of NSCLC. Within this study, the inhibitory activity of (+)-anthrabenzoxocinone ((+)-ABX), an oxygenated anthrabenzoxocinone compound derived from Streptomyces, against NSCLC is demonstrated for the first time both in vitro and in vivo. Mechanistically, it is confirmed that the PI3K/AKT/mTOR signaling pathway is targeted and suppressed by (+)-ABX, resulting in the induction of S and G2/M phase arrest, apoptosis, and autophagy in NSCLC cells. Additionally, the augmentation of intracellular ROS levels by (+)-ABX is revealed, further contributing to the inhibition of the signaling pathway and exerting inhibitory effects on tumor growth. The findings presented in this study suggest that (+)-ABX possesses the potential to serve as a lead compound for the treatment of NSCLC.


Subject(s)
Apoptosis , Autophagy , Carcinoma, Non-Small-Cell Lung , Cell Cycle Checkpoints , Lung Neoplasms , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Signal Transduction , TOR Serine-Threonine Kinases , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , TOR Serine-Threonine Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Humans , Apoptosis/drug effects , Autophagy/drug effects , Lung Neoplasms/drug therapy , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Signal Transduction/drug effects , Phosphatidylinositol 3-Kinases/metabolism , Animals , Cell Line, Tumor , Cell Cycle Checkpoints/drug effects , Mice, Nude , Mice , Cell Proliferation/drug effects , Mice, Inbred BALB C , Xenograft Model Antitumor Assays , Reactive Oxygen Species/metabolism , Antineoplastic Agents/pharmacology
9.
Exp Cell Res ; 420(1): 113341, 2022 11 01.
Article in English | MEDLINE | ID: mdl-36075445

ABSTRACT

Esophageal squamous cell carcinoma (ESCC) is a major cause of cancer-related deaths. We have previously connected a non-sulfated glycosaminoglycan, hyaluronic acid (HA), with a common hydrogen sulfide (H2S) donor, 5-(4-hydroxyphenyl)-3H-1,2-dithiol-3-thione (ADT-OH), to reconstruct a novel conjugate, HA-ADT. In this study, we determined the effect of HA-ADT on the growth of ESCC. Our data suggested that HA-ADT exerted more potent effects than sodium hydrosulfide (NaHS, a fast H2S-releasing donor) and morpholin-4-ium (4-methoxyphenyl)-morpholin-4-ylsulfanylidenesulfido-λ5-phosphane (GYY4137, a slow H2S-releasing donor) on inhibiting the viability, proliferation, migration, and invasion of human ESCC cells. HA-ADT increased apoptosis by suppressing the protein expressions of phospho (p)-Ser473-protein kinase B (PKB/AKT), p-Tyr199/Tyr458-phosphatidylinositol 3-kinase (PI3K), and p-Ser2448-mammalian target of rapamycin (mTOR), but suppressed autophagy through the inhibition of the protein levels of p-Ser552-ß-catenin, p-Ser9-glycogen synthase kinase-3ß (GSK-3ß), and Wnt3a in human ESCC cells. In addition, HA-ADT was more effective in terms of the growth inhibition of human ESCC xenograft tumor than NaHS and GYY4137. In conclusion, HA-ADT can suppress ESCC progression via apoptosis promotion and autophagy inhibition. HA-ADT might be efficacious for the treatment of cancer.


Subject(s)
Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Hydrogen Sulfide , Apoptosis , Autophagy , Cell Line, Tumor , Cell Proliferation , Esophageal Neoplasms/pathology , Esophageal Squamous Cell Carcinoma/drug therapy , Glycogen Synthase Kinase 3 beta , Humans , Hyaluronic Acid/pharmacology , Hydrogen Sulfide/pharmacology , Morpholines , Organothiophosphorus Compounds , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Sulfides , TOR Serine-Threonine Kinases/metabolism , Thiones , beta Catenin
10.
Support Care Cancer ; 31(12): 684, 2023 Nov 10.
Article in English | MEDLINE | ID: mdl-37945919

ABSTRACT

PURPOSE: To examine the relationship between self-disclosure, coping styles, and benefit finding (BF) among caregivers of cancer patients. The study also aimed to identify the factors influencing BF and the impact of coping styles on the relationship between self-disclosure and BF. METHODS: Convenience sampling was used to select 300 caregivers of cancer patients aged greater than 18 years from October 2022 to April 2023 in Chengdu, China. The demographic and clinical characteristics questionnaire, the Benefit Finding Scale (BFS), the Distress Disclosure Index Scale (DDI), and the Simple Coping Style Scale (SCSQ) for caregivers were included in this study. Descriptive statistics, t-tests, one-way analysis of variance, Pearson's correlation analyses, and multiple linear regression models were used. The effect of mediation was tested by the PROCESS macro (Model 4) for SPSS 26.0 by Hayes using 5000 bootstrap samples. RESULTS: There were 292 valid questionnaires (effective response rate 97.33%). The total scores of BF, self-disclosure, negative coping style, and positive coping style of caregivers were 67.77 ± 14.78, 38.23 ± 8.59, 19.68 ± 5.98, and 9.88 ± 4.18, respectively; Pearson's correlation analysis showed that BF was positively correlated with self-disclosure, positive coping, and negatively correlated with negative coping; multiple linear regression analysis showed that self-disclosure, positive coping, and negative coping were influential factors of BF. The results revealed that the effect of self-disclosure on BF was partly mediated by coping styles. It also confirmed that the mediation effect accounted for 54.03% of the total effect. CONCLUSION: The BF of caregivers is at a moderate level. Self-disclosure may influence BF partly because of coping styles.


Subject(s)
Adaptation, Psychological , Caregivers , Disclosure , Neoplasms , Humans , Caregivers/psychology , East Asian People
11.
Biochem Genet ; 2023 Nov 01.
Article in English | MEDLINE | ID: mdl-37910330

ABSTRACT

Leukoaraiosis (LA) appears as white matter hyperintensities on T2-weighted brain magnetic resonance imaging scans. Age and hypertension are considered the primary risk factors for LA, but its pathogenesis remains uncertain. This study aims to investigate the correlation between the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and LA. A total of 140 patients with LA and 136 neuroimaging alteration-free controls were recruited in a case-control study. ACE I/D polymorphism was determined using the polymerase chain reaction method. The allele and genotype distributions of the ACE I/D polymorphism were significantly different between subjects with and without LA. Significant difference was observed in the genotypic distribution between LA patients and controls for recessive and additive models. A statistically significant association remained apparent after adjusting for potential risk factors (D/D vs. I/D + I/I: adjusted OR 3.251, 95% CI 1.185-8.918; D/D vs. I/I: adjusted OR 3.277, 95% CI 1.187-9.047). Our results indicate that the D/D genotype and D allele are important risk factors for LA. Future studies with larger populations are needed to validate our results.

12.
Small ; 18(15): e2108055, 2022 04.
Article in English | MEDLINE | ID: mdl-35253981

ABSTRACT

Radical-containing frameworks (RCFs) have emerged as promising functional materials in various fields due to the combination of the highly ordered frame structure and the fascinating property of organic radicals. Here, the first example of radical-containing supramolecular organic frameworks (SOFs) fabricated by the chaotropic effect between closo-dodecaborate cluster (B12 H122- ) and 2,4,6-tri(4-pyridyl)-1,3,5-triazine (TPT3+ ) is presented. The SOFs can be easily synthesized by stirring the B12 H122- and the TPT3+ in aqueous solution through self-assembly. Upon 435 nm light irradiation, the SOFs exhibits photochromic behavior from slight yellow (SOF-1) to dark purple (SOF-2). Electron paramagnetic resonance spectroscopy also reveals that stable radicals are generated in situ after light irradiation. Powder X-ray diffraction demonstrates the SOFs maintain their structural stabilities upon light irradiation. More interestingly, the radical-containing SOFs exhibit efficient photothermal effect under 660 nm light irradiation, which can be applied as photothermal agent for antibacterial application both in vitro and in vivo. This work highlights the construction of RCFs through supramolecular self-assembly, which may arouse applications in energy, catalysis, photoluminescence, and biomedical fields.


Subject(s)
Photothermal Therapy , Catalysis
13.
Indian J Med Res ; 156(3): 529-534, 2022 09.
Article in English | MEDLINE | ID: mdl-36751749

ABSTRACT

Background & objectives: Recently, there has been a surge to develop new devices and techniques for the diagnosis of peripheral pulmonary lesions such as the combination of LungPoint navigation and endobronchial ultrasound with a guide sheath (EBUS-GS). The present study aimed to explore the diagnostic value of LungPoint navigation in combination with EBUS-GS and rapid on-site evaluation (ROSE) particularly for peripheral pulmonary nodules. Methods: Patients (n=108) with pulmonary nodules (10 mm ≤ nodal diameter ≤30 mm) presenting to Henan Provincial People's Hospital were detected using chest computed tomographic (CT) scanning and bronchoscopy. All patients were evaluated using LungPoint navigation, EBUS-GS and ROSE techniques to evaluate the positive rate of combined diagnosis using the three methods. Results: A total of 108 patients participated in this study and successfully underwent all the three procedures. Of these, 82 patients were accurately diagnosed, making the overall diagnostic rate of 75.9 per cent for combined LungPoint navigation, EBUS-GS, and ROSE analyses. Further subgroup analysis of the diagnostic rate of the three combined techniques were conducted based on the size of the nodules which showed a diagnostic rate of 65.3 per cent for 10 mm ≤ nodule diameter ≤20 mm and 85.7 per cent for 20 mm ≤ nodal diameter ≤30 mm. Of the 108 patients, 85 had solid nodules and 23 had ground-glass nodules; the positive rate of diagnosis of solid nodules was the highest. The patients ultimately were diagnosed with lung cancer with a positive rate of 83.5 per cent. The sensitivity, specificity and positive and negative predicted values for ROSE were 90.3, 78.3, 84.8 and 83.6 per cent, respectively. Interpretation & conclusions: The combined use of the three techniques can effectively shorten the duration of the total diagnosis period and improve the safety of diagnosis without affecting the detection rate.


Subject(s)
Lung Neoplasms , Rapid On-site Evaluation , Humans , Endosonography/methods , Bronchoscopy/methods , Retrospective Studies
15.
Mamm Genome ; 32(2): 115-122, 2021 04.
Article in English | MEDLINE | ID: mdl-33755782

ABSTRACT

Atherosclerosis was an important pathophysiological basis of atherothrombotic stroke, and phosphodiesterase 4D (PDE4D) polymorphism (SNP83/rs966221) was reported to be associated with the susceptibility to atherothrombotic stroke. Aim of the present study was to explore the potential association between SNP83 and carotid atherosclerosis (CAS). 204 southern Chinese Han participants were divided into two groups according to the carotid intima-media thickness (IMT) of the carotid artery: CAS group (carotid IMT ≥ 1.0 mm) and non-CAS group (carotid IMT < 1.0 mm). Carotid IMT was measured by color Doppler ultrasound. The PDE4D SNP83 polymorphism was determined by SNaPshot technique. Our study found that SNP83 was associated significantly with CAS susceptibility under the dominant, overdominant and codominant models. After adjusting for age, gender, low-density lipoprotein cholesterol, Hemoglobin A1c, cigarette smoking, hypertension history, and diabetes mellitus history, the association still remained significant (dominant model: crude OR = 2.373, 95% CI: 1.268-4.442, P = 0.007; adjusted OR = 3.129, 95% CI: 1.104-8.866, P = 0.032; overdominant model: crude OR = 1.968, 95% CI: 1.043-3.714, P = 0.037; adjusted OR = 2.854, 95% CI: 1.005-8.108, P = 0.049; codominant: crude OR = 2.102, 95% CI: 1.110-3.979, P = 0.023; adjusted OR = 2.984, 95% CI: 1.047-8.502, P = 0.041). Carotid IMT of carriers with CT + CC genotypes was higher than carriers with TT genotype (P = 0.016). Our results indicated that the SNP83/rs966221 located on PDE4D gene was significantly associated between CAS susceptibility and carotid IMT independently of conventional risk factors in a southern Chinese Han population.


Subject(s)
Asian People/genetics , Carotid Artery Diseases/genetics , Cyclic Nucleotide Phosphodiesterases, Type 4/genetics , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Alleles , Biomarkers , Carotid Artery Diseases/diagnosis , Carotid Intima-Media Thickness , China , Genetic Association Studies , Genotype , Humans , Risk Factors
16.
FASEB J ; 34(5): 6038-6054, 2020 05.
Article in English | MEDLINE | ID: mdl-32202355

ABSTRACT

Transfusion of autologous blood is a timesaving, convenient, safe, and effective therapy from a clinical perspective, and often employed for the treatment of diabetic patients. Stabilization of HIF-1α has been widely reported to be a critical factor in the improvement of wound healing in diabetes. Therefore, our study reveals the roles of improved autologous blood in wound healing in diabetes, through autologous blood transfusion in a mouse model. Initially, BALB/c mice were subjected to streptozotocin for diabetic mouse model establishment. Diabetic mice were transfused with improved or standard autologous blood in perfusion culture system. Roles of improved autologous blood in mediating HIF-1α pathway were determined by measuring expression of VEGF, EGF, HIF-1α, and HSP-90. In order to assess the detailed regulatory mechanism of improved autologous blood in perspective of wound healing, cell proliferation, migration and cell cycle, fibroblasts isolated from diabetic mice were transfected with HIF-1α siRNA. Mice transfused with improved autologous blood exhibited increased levels of CD31 and α-SMA in skin tissues, and reduced TNF-α, IL-1ß, and IL-6 levels, indicating that improved autologous blood promoted wound healing ability and reduced the release of inflammatory factors. Diabetic mice transfused with improved autologous blood presented activated HIF-1α pathway. The survival rate, proliferation, and migration of fibroblasts were elevated via activation of the HIF-1α pathway. Taken together, improved blood preservation solution could enhance the oxygen carrying capacity of red blood cells and wound healing in mice with diabetes, which is achieved through regulation of HIF-1α pathway.


Subject(s)
Blood Preservation/methods , Blood Transfusion, Autologous/methods , Diabetes Mellitus, Experimental/therapy , Disease Models, Animal , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Neovascularization, Physiologic , Wound Healing , Animals , Cell Movement , Cell Proliferation , Diabetes Mellitus, Experimental/pathology , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Male , Mice
17.
J Gastroenterol Hepatol ; 36(2): 474-481, 2021 Feb.
Article in English | MEDLINE | ID: mdl-32677707

ABSTRACT

BACKGROUND AND AIM: Remimazolam tosilate (RT) is a new short-acting GABA(A) receptor agonist, having potential to be an effective option for procedural sedation. Here, we aimed to compare the efficacy and safety of RT with propofol in patients undergoing upper gastrointestinal endoscopy. METHODS: This positive-controlled, non-inferiority, phase III trial recruited patients at 17 centers, between September 2017 and November 2017. A total of 384 patients scheduled to undergo upper gastrointestinal endoscopy were randomly assigned to receive RT or propofol. Primary endpoint was the success rate of sedation. Adverse events (AEs) were recorded to evaluate safety. RESULTS: The success rate of sedation in the RT group was non-inferior to that in the propofol group (97.34% vs 100.00%; difference in rate -2.66%, 95% CI -4.96 to -0.36, meeting criteria for non-inferiority). Patients in the RT group had longer time to adequate sedation (P < 0.0001) but shorter time to fully alert (P < 0.0001) than that in the propofol group. The incidences of hypotension (13.04% vs 42.86%, P < 0.0001), treatment-related hypotension (0.54% vs 5.82%, P < 0.0001), and respiratory depression (1.09% vs 6.88%, P = 0.0064) were significantly lower in the RT group. AEs were reported in 74 (39.15%) patients in the RT group and 114 (60.32%) patients in the propofol group, with significant difference (P < 0.0001). CONCLUSION: This trial established non-inferior sedation success rate of RT compared with propofol. RT allows faster recovery from sedation compared with propofol. The safety profile is favorable and appears to be superior to propofol, indicating that it was feasible and well tolerated for patients.


Subject(s)
Benzodiazepines/administration & dosage , Conscious Sedation/methods , Endoscopy, Gastrointestinal , Adult , Aged , Anesthesia Recovery Period , Benzodiazepines/adverse effects , Feasibility Studies , Female , Humans , Hypertension/chemically induced , Hypertension/epidemiology , Hypnotics and Sedatives/administration & dosage , Hypnotics and Sedatives/adverse effects , Incidence , Male , Middle Aged , Propofol/administration & dosage , Propofol/adverse effects , Respiratory Insufficiency/chemically induced , Respiratory Insufficiency/epidemiology , Safety
18.
BMC Anesthesiol ; 21(1): 268, 2021 11 04.
Article in English | MEDLINE | ID: mdl-34736416

ABSTRACT

BACKGROUND: The anatomical dimensions of the lumbar dural sac determine the sensory block level of spinal anesthesia; however, whether they show the same predictive value during continuous epidural anesthesia (CEA) remains undetermined. We designed the present study to verify the efficacy of the anatomical dimensions of the lumbar dural sac in predicting the sensory block level during labor analgesia. METHODS: A total of 122 parturients with singleton pregnancies requesting labor analgesia were included in this study. The lumbar dural sac diameter (DSD), lumbar dural sac length (DSL), lumbar dural sac surface area (DSA), and lumbar dural sac volume (DSV) were measured with an ultrasound color Doppler diagnostic apparatus. CEA was performed at the L2-L3 interspace. After epidural cannulation, an electronic infusion pump containing 0.08% ropivacaine and sufentanil 0.4 µg/ml was connected. The sensory block level was determined with alcohol-soaked cotton, a cotton swab, and a pinprick. The analgesic efficacy of CEA was determined with a visual analog scale (VAS). The parturients were divided into two groups, "ideal analgesia" and "nonideal analgesia," and the groups were compared by t test. Pearson's correlation was performed to evaluate the association between the anatomical dimensions of the lumbar dural sac and sensory block level. Multiple linear regression analysis was used to create a model for predicting the sensory block level. RESULTS: In the ideal analgesia group, the height, DSL, DSA, DSV and DSD were significantly smaller, and the body mass index (BMI) was significantly larger (P < 0.05). In addition, the DSL demonstrated the strongest correlation with the peak level of pain block (r = - 0.816, P < 0.0001; Fig. 2A), temperature block (r = - 0.874, P < 0.0001; Fig. 3A) and tactile block (r = - 0.727, P < 0.0001; Fig. 4A). Finally, the multiple linear regression analysis revealed that DSL and BMI contributed to predicting the peak sensory block level. CONCLUSION: In conclusion, our study shows that the sensory block level of CEA is higher when the DSL, DSA, DSV and DSD of puerperae are lower. DSL and BMI can be treated as predictors of the peak sensory block level in CEA during labor analgesia.


Subject(s)
Analgesia, Epidural/methods , Analgesia, Obstetrical/methods , Dura Mater/diagnostic imaging , Lumbar Vertebrae/diagnostic imaging , Adolescent , Adult , Analgesics, Opioid/administration & dosage , Anesthetics, Local/administration & dosage , Body Mass Index , Female , Humans , Labor, Obstetric , Middle Aged , Pregnancy , Ropivacaine/administration & dosage , Sufentanil/administration & dosage , Ultrasonography, Doppler, Color , Young Adult
19.
J Med Internet Res ; 23(12): e29167, 2021 12 07.
Article in English | MEDLINE | ID: mdl-34878992

ABSTRACT

BACKGROUND: Walking is a simple but beneficial form of physical activity (PA). Self-monitoring and providing information about social norms are the 2 most widely used "mobile health (mHealth)" strategies to promote walking behavior. However, previous studies have failed to discriminate the effect of self-monitoring from the combination of the 2 strategies, and provide practical evidence within Chinese culture. Some essential moderators, such as gender and group identity, were also overlooked. OBJECTIVE: We aimed to investigate the effectiveness of social norm and self-monitoring interventions for walking behavior and assess the moderating effects of gender and group identity, which could guide optimal mHealth intervention projects in China. METHODS: In 2 longitudinal tracking studies (study 1, 22 days; study 2, 31 days), Chinese college students wore trackers for at least 8 hours per day (MASAI 3D Pedometer and Xiaomi Wristband 2) to record their daily step counts in baseline, intervention, and follow-up stages. In each study, participants (study 1: n=117, 54% female, mean age 25.60 years; study 2: n=180, 51% female, mean age 22.60 years) were randomly allocated to 1 of the following 3 groups: a self-monitoring group and 2 social norm intervention groups. In the 2 intervention groups and during the intervention stage, participants received different social norm information regarding group member step rankings corresponding to their grouping type of social norm information. In study 1, participants were grouped by within-group member PA levels (PA consistent vs PA inconsistent), and in study 2, participants were grouped by their received gender-specific social norm information (gender consistent vs gender inconsistent). Piece-wise linear mixed models were used to compare the difference in walking steps between groups. RESULTS: In study 1, for males in the self-monitoring group, walking steps significantly decreased from the baseline stage to the intervention stage (change in slope=-1422.16; P=.02). However, additional social norm information regardless of group consistency kept their walking unchanged. For females, social norm information did not provide any extra benefit beyond self-monitoring. Females exposed to PA-inconsistent social norm information even walked less (slope during the intervention=-122.18; P=.03). In study 2, for males, a similar pattern was observed, with a decrease in walking steps in the self-monitoring group (change in slope=-151.33; P=.08), but there was no decrease in the 2 social norm intervention groups. However, for females, gender-consistent social norm information decreased walking steps (slope during the intervention=-143.68; P=.03). CONCLUSIONS: Both gender and group identity moderated the effect of social norm information on walking. Among females, social norm information showed no benefit for walking behavior and may have exerted a backfire effect. Among males, while walking behavior decreased with self-monitoring only, the inclusion of social norm information held the level of walking behavior steady.


Subject(s)
Social Norms , Walking , Adult , China , Exercise , Female , Humans , Male , Students , Young Adult
20.
Mikrochim Acta ; 188(9): 308, 2021 Aug 27.
Article in English | MEDLINE | ID: mdl-34453216

ABSTRACT

The ternary NiCoAl hydrotalcite (NiCoAl-LDH) was combined with carboxylic multi-walled carbon nanotube (MWCNT) to fabricate a novel electrochemical sensor for simultaneously determining the co-existing trace phenolic substances. The morphology, structure, and electrochemical behavior of the as-prepared materials were characterized by various techniques. Benefitting from the great conductivity of MWCNT and high electrocatalytic activity of NiCoAl-LDH for phenolic substances, the advanced MWCNT/NiCoAl-LDH sensor presented a fast response, high sensitivity, excellent stability, and satisfactory replicability. The sensor offered good linear responses in the ranges1.50~600 µM to hydroquinone (HQ), 5.00~1.03 × 103 µM to catechol (CC), and 6.00 × 10-2~250 µM to bisphenol A (BPA). The detection limits of HQ, CC, and BPA were 0.4, 0.8, and 6. × 10-3 µM (S/N = 3), respectively. In environmental water, the sensor achieved satisfactory recoveries for the simultaneous detection of HQ (98.6~101%), CC (98.0~101%), and BPA (97.5~101%), with relative standard deviations less than 4.4%.

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