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1.
Ren Fail ; 46(2): 2365396, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38874150

ABSTRACT

OBJECTIVE: The aim of this study was to investigate the potential importance of complement system activation, with particular emphasis on the complement alternative pathway (AP), in the pathogenesis of hypertensive renal damage. METHODS: Serum complement C3, complement Factor H (CFH) and AP activation were assessed in 66 participants with established essential hypertension with renal damage (RD). Fifty-nine patients with age- and sex-matched essential hypertension without renal damage (NRD) and 58 healthy participants (normal) were selected. RESULTS: Our study revealed that C3 and AP50 continuously increased from normal to NRD to RD (p < 0.05, respectively), while CFH was significantly lower than that in NRD and healthy participants (p < 0.05, respectively). After multifactorial logistic regression analysis corrected for confounders, elevated serum C3 (p = 0.001) and decreased CFH (p < 0.001) were found to be independent risk factors for hypertension in healthy participants; elevated serum C3 (p = 0.034), elevated AP50 (p < 0.001), decreased CFH (p < 0.001), increased age (p = 0.011) and increased BMI (p = 0.013) were found to be independent risk factors for the progression of hypertension to hypertensive renal damage; elevated serum C3 (p = 0.017), elevated AP50 (p = 0.023), decreased CFH (p = 0.005) and increased age (p = 0.041) were found to be independent risk factors for the development of hypertensive renal damage in healthy participants. CONCLUSION: Abnormal activation of complement, particularly complement AP, may be a risk factor for the development and progression of hypertensive renal damage.


Subject(s)
Complement C3 , Complement Factor H , Humans , Male , Female , Middle Aged , Case-Control Studies , Complement C3/metabolism , Complement C3/analysis , Risk Factors , Aged , Adult , Hypertension/complications , Hypertension/blood , Complement Activation , Essential Hypertension/blood , Essential Hypertension/complications , Essential Hypertension/physiopathology , Logistic Models , Complement Pathway, Alternative , Disease Progression
2.
J Ethnopharmacol ; 333: 118414, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38830451

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Hepatocellular Carcinoma (HCC) is an aggressive killer worldwide with high incidence and mortality. The herb Chloranthus fortunei (A. Gray) Solms-Laub is known as "Si Ji Feng" and is classified as a Feng-type medicine in classic Yao medicines. According to Yao's medical beliefs, Chloranthus fortunei has the functions of dispelling Feng, regulating qi, detoxifying, promoting blood circulation, etc. Folk uses its decoctions to treat stagnant liver conditions, such as liver abscesses, cirrhosis, hepatitis, and liver cancer. However, the bioactivity and mechanisms of Chloranthus fortunei extract against HCC have not been reported. AIM OF THE STUDY: To investigate the anti-HCC bioactivity and potential mechanism of the extract of Chloranthus fortunei (CFS). MATERIALS AND METHODS: Using 70% ethanol for reflux extraction of CFS resulted in the CFS ethanol extract, followed by sequential extractions with petroleum ether, chloroform, ethyl acetate, and n-butanol, yielding four fractions. The CCK-8 assay was utilized to examine the cytotoxic effects of 4 fractions on MHCC97-H and HepG2 cells, exploring the most effective component, namely petroleum ether extracts of CFS (PECFS). The major active ingredients of PECFS were identified using LC/MS technology, and the impact on cell proliferation and apoptosis in HCC cells was studied. The key genes and proteins in the pathway were validated using RT-PCR and Western blotting. BALB/c nude mice were chosen for tumor xenotransplantation and PECFS therapy. hinders the proliferation of HCC cells and promotes apoptosis. RESULTS: Among the four fractions, it was found that PECFS have the highest antiproliferative activity against MHCC97-H and HepG2 cells (IC50 = 13.86, 10.55 µg/mL), with sesquiterpene compounds being the primary active constituents. The antiproliferative activity of PECFS on HCC cells was linked to the inhibition of cell cloning, invasion, and metastasis abilities, as well as the arrest of the cell cycle at the G2/M phase. Additionally, exerts pro-apoptotic effects on HCC cells by upregulating the pro-apoptotic protein Bax, downregulating the anti-apoptotic protein Bcl-2, and activating the expression of the Caspase family. Moreover, protein and m-RNA expression data showed that PECFS inhibits HCC cell proliferation and promotes apoptosis by regulating the PI3K/AKT/mTOR pathway. Besides, after PECFS treatment, tumor growth in nude mice was suppressed. CONCLUSION: PECFS can inhibit the viability of HCC cells by acting on the PI3K/AKT/mTOR pathway, demonstrating anti-tumor potential. This study's findings suggest that PECFS may represent a promising source of novel agents for liver cancer treatment, providing scientific evidence for the traditional application of CFS in treating HCC.

3.
Sci Rep ; 14(1): 12437, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38816559

ABSTRACT

The min-max multi-vehicle Chinese postman problem is an NP-hard problem, which is widely used in path planning problems based on road network graphs, such as urban road structure probing planning, urban road underground cavity detection planning, high-voltage line inspection planning, and so on. With the rapid increase in the number of nodes and connections of road network graph, the solution time and path equilibrium constraints pose new challenges to the problem solving. In this paper, we propose a critical-edge tabu search algorithm, CTA-kroutes, for solving the min-max multi-vehicle postman problem for large-scale road networks. First, the initial solution with balanced path lengths is obtained by segmenting the Eulerian paths; second, the critical edges are moved in the initial solution to construct the neighborhood solution, and the tabu search algorithm is used to find the optimal solution iteratively; and lastly, the solution optimization algorithm is used at the end of each iteration to de-duplicate and optimally reconstruct the current search result. Experiments show that the CTA-kroutes algorithm can effectively improve the equalization of multi-vehicle paths and its applicability to large-scale road networks.

4.
Int J Biol Macromol ; 269(Pt 2): 131747, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38670196

ABSTRACT

Given the broad biological effects of the Hedgehog (Hh) pathway, there is potential clinical value in local application of Hh pathway modulators to restrict pathway activation of target tissues and avoid systemic pathway activation. One option to limit Hh pathway activation is using fibrin hydrogels to deliver pathway modulators directly to tissues of interest, bypassing systemic distribution of the drug. In this study, we loaded the potent Hh pathway agonist, SAG21k, into fibrin hydrogels. We describe the binding between fibrin and SAG21k and achieve sustained release of the drug in vitro. SAG21k-loaded fibrin hydrogels exhibit strong biological activity in vitro, using a pathway-specific reporter cell line. To test in vivo activity, we used a mouse model of facial nerve injury. Application of fibrin hydrogels is a common adjunct to surgical nerve repair, and the Hh pathway is known to play an important role in facial nerve injury and regeneration. Local application of the Hh pathway agonist SAG21k using a fibrin hydrogel applied to the site of facial nerve injury successfully activates the Hh pathway in treated nerve tissue. Importantly, this method appears to avoid systemic pathway activation when Hh-responsive organs are analyzed for transcriptional pathway activation. This method of local tissue Hh pathway agonist administration allows for effective pathway targeting surgically accessible tissues and may have translational value in situations where supranormal pathway activation is therapeutic.


Subject(s)
Facial Nerve Injuries , Fibrin , Hedgehog Proteins , Hydrogels , Signal Transduction , Animals , Hydrogels/chemistry , Hydrogels/pharmacology , Hedgehog Proteins/metabolism , Fibrin/chemistry , Mice , Facial Nerve Injuries/drug therapy , Signal Transduction/drug effects , Humans
5.
Front Neurosci ; 18: 1376570, 2024.
Article in English | MEDLINE | ID: mdl-38567281

ABSTRACT

White matter tract segmentation is a pivotal research area that leverages diffusion-weighted magnetic resonance imaging (dMRI) for the identification and mapping of individual white matter tracts and their trajectories. This study aims to provide a comprehensive systematic literature review on automated methods for white matter tract segmentation in brain dMRI scans. Articles on PubMed, ScienceDirect [NeuroImage, NeuroImage (Clinical), Medical Image Analysis], Scopus and IEEEXplore databases and Conference proceedings of Medical Imaging Computing and Computer Assisted Intervention Society (MICCAI) and International Symposium on Biomedical Imaging (ISBI), were searched in the range from January 2013 until September 2023. This systematic search and review identified 619 articles. Adhering to the specified search criteria using the query, "white matter tract segmentation OR fiber tract identification OR fiber bundle segmentation OR tractography dissection OR white matter parcellation OR tract segmentation," 59 published studies were selected. Among these, 27% employed direct voxel-based methods, 25% applied streamline-based clustering methods, 20% used streamline-based classification methods, 14% implemented atlas-based methods, and 14% utilized hybrid approaches. The paper delves into the research gaps and challenges associated with each of these categories. Additionally, this review paper illuminates the most frequently utilized public datasets for tract segmentation along with their specific characteristics. Furthermore, it presents evaluation strategies and their key attributes. The review concludes with a detailed discussion of the challenges and future directions in this field.

6.
Brain Commun ; 6(2): fcae126, 2024.
Article in English | MEDLINE | ID: mdl-38665963

ABSTRACT

We previously reported interhemispheric structural hyperconnectivity bypassing the corpus callosum in children born extremely preterm (<28 weeks) versus term children. This increased connectivity was positively associated with language performance at 4-6 years of age in our prior work. In the present study, we aim to investigate whether this extracallosal connectivity develops in extremely preterm infants at term equivalent age by leveraging a prospective cohort study of 350 very and extremely preterm infants followed longitudinally in the Cincinnati Infant Neurodevelopment Early Prediction Study. For this secondary analysis, we included only children born extremely preterm and without significant brain injury (n = 95). We use higher-order diffusion modelling to assess the degree to which extracallosal pathways are present in extremely preterm infants and predictive of later language scores at 22-26 months corrected age. We compare results obtained from two higher-order diffusion models: generalized q-sampling imaging and constrained spherical deconvolution. Advanced MRI was obtained at term equivalent age (39-44 weeks post-menstrual age). For structural connectometry analysis, we assessed the level of correlation between white matter connectivity at the whole-brain level at term equivalent age and language scores at 2 years corrected age, controlling for post-menstrual age, sex, brain abnormality score and social risk. For our constrained spherical deconvolution analyses, we performed connectivity-based fixel enhancement, using probabilistic tractography to inform statistical testing of the hypothesis that fibre metrics at term equivalent age relate to language scores at 2 years corrected age after adjusting for covariates. Ninety-five infants were extremely preterm with no significant brain injury. Of these, 53 had complete neurodevelopmental and imaging data sets that passed quality control. In the connectometry analyses adjusted for covariates and multiple comparisons (P < 0.05), the following tracks were inversely correlated with language: bilateral cerebellar white matter and middle cerebellar peduncles, bilateral corticospinal tracks, posterior commissure and the posterior inferior fronto-occipital fasciculus. No tracks from the constrained spherical deconvolution/connectivity-based fixel enhancement analyses remained significant after correction for multiple comparisons. Our findings provide critical information about the ontogeny of structural brain networks supporting language in extremely preterm children. Greater connectivity in more posterior tracks that include the cerebellum and connections to the regions of the temporal lobes at term equivalent age appears to be disadvantageous for language development.

7.
Pediatr Surg Int ; 40(1): 62, 2024 Mar 02.
Article in English | MEDLINE | ID: mdl-38430253

ABSTRACT

PURPOSE: Paraovarian cysts in children and adolescents can be challenging to accurately diagnose prior to surgery. Our objective is to outline the clinical characteristics of paraovarian cysts and enhance the precision of diagnosing paraovarian cysts in this age group. METHODS: We retrospectively analyzed all patients with paraovarian cysts who underwent surgery in our department from 2013 to 2021. The review focused on demographic characteristics, clinical manifestations, intraoperative findings, and postoperative pathology of these patients. RESULTS: This cohort was composed of 38 children with paraovarian cysts. The average diameter of the cysts was 4.8 cm (range 0.5-10 cm). Among the cases, 25 (65.8%) had adnexal torsion. Postoperative pathology showed that all cases were simple cysts with serous fluid. After the procedure, the patients were monitored for a period ranging from 12 to 108 months. B-ultrasound and physical examination did not reveal any significant abnormalities. CONCLUSIONS: B-ultrasound can help diagnose paraovarian cysts by detecting slight deviation movement between the cyst and the uterus. The presence of adnexa torsion in children and adolescents with paraovarian cysts does not depend on BMI, but rather on the size of cysts. Laparoscopic cyst removal has proven to be an effective surgical approach with favorable outcomes.


Subject(s)
Cysts , Laparoscopy , Parovarian Cyst , Female , Child , Humans , Adolescent , Retrospective Studies , Parovarian Cyst/pathology , Parovarian Cyst/surgery , Cysts/surgery , Ultrasonography
8.
Neuroimage ; 291: 120579, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38537766

ABSTRACT

Very preterm (VPT) infants (born at less than 32 weeks gestational age) are at high risk for various adverse neurodevelopmental deficits. Unfortunately, most of these deficits cannot be accurately diagnosed until the age of 2-5 years old. Given the benefits of early interventions, accurate diagnosis and prediction soon after birth are urgently needed for VPT infants. Previous studies have applied deep learning models to learn the brain structural connectome (SC) to predict neurodevelopmental deficits in the preterm population. However, none of these models are specifically designed for graph-structured data, and thus may potentially miss certain topological information conveyed in the brain SC. In this study, we aim to develop deep learning models to learn the SC acquired at term-equivalent age for early prediction of neurodevelopmental deficits at 2 years corrected age in VPT infants. We directly treated the brain SC as a graph, and applied graph convolutional network (GCN) models to capture complex topological information of the SC. In addition, we applied the supervised contrastive learning (SCL) technique to mitigate the effects of the data scarcity problem, and enable robust training of GCN models. We hypothesize that SCL will enhance GCN models for early prediction of neurodevelopmental deficits in VPT infants using the SC. We used a regional prospective cohort of ∼280 VPT infants who underwent MRI examinations at term-equivalent age from the Cincinnati Infant Neurodevelopment Early Prediction Study (CINEPS). These VPT infants completed neurodevelopmental assessment at 2 years corrected age to evaluate cognition, language, and motor skills. Using the SCL technique, the GCN model achieved mean areas under the receiver operating characteristic curve (AUCs) in the range of 0.72∼0.75 for predicting three neurodevelopmental deficits, outperforming several competing models. Our results support our hypothesis that the SCL technique is able to enhance the GCN model in our prediction tasks.


Subject(s)
Connectome , Infant, Premature , Infant , Infant, Newborn , Humans , Child, Preschool , Prospective Studies , Brain/diagnostic imaging , Infant, Very Low Birth Weight
9.
Nurse Educ Pract ; 76: 103896, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38377933

ABSTRACT

AIM: To explore the application effect of competency-based education (CBE) combined with multi-disciplinary team (MDT) teaching mode in respiratory rehabilitation nursing teaching. BACKGROUND: Respiratory rehabilitation, as an important non drug treatment for chronic respiratory disease, started late in China, with low implementation rate in hospitals and insufficient knowledge of nursing staff. Therefore, it is urgent to cultivate high professional level nurses with strong professional ability. DESIGN: A randomized controlled trial. METHODS: We selected nurses from the respiratory and critical care department at a Grade III, Level A hospital in Beijing, who participated in the respiratory rehabilitation training program between March 2020 and August 2022, as our study participants. Participants were grouped using a random number method. Nurses who participated in the study from March 2020 to May 2021 were set as the control group, and the nurses who participated in the study from June 2021 to August 2022 were set as the test group. The control group used traditional teaching methods, and the test group used the CBE combined MDT teaching model. At the end of the test, the theory, operating skills, satisfaction and core competence were assessed. RESULTS: After training, the theoretical examination score of the test group (93.71 ± 1.94) was higher than that of the control group (92.37 ± 1.92), the operational examination score of the test group (93.11 ± 2.12) was higher than that of the control group (91.61 ± 1.93), the overall teaching satisfaction of the test group (4.45 ± 0.50) was higher than that of the control group (4.13 ± 0.57), and the total score of the core competence of the test group (148.73 ± 7.08) was higher than that of the control group (141.02 ± 6.41). The difference between the two groups was statistically significant (P<0.05). CONCLUSION: CBE combined with MDT teaching mode has a good effect in Pulmonary and Critical Care Medicine (PCCM) respiratory rehabilitation nursing teaching.


Subject(s)
Competency-Based Education , Rehabilitation Nursing , Humans , China , Clinical Competence
10.
Heliyon ; 10(3): e25447, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38322978

ABSTRACT

Objectives: This study aimed to determine the occurrence rate of malalignment of tibial prosthesis and explore the influencing factors. Methods: 296 patients from Southern China who underwent total knee arthroplasty (TKA) were selected as the research objects. Their general demographic data were recorded. The tibial bowing angle (TBA), tibial length, medial proximal tibial angle (MPTA), tibial plateau shift angle (TPSA), tibial bone loss, lateral distal tibial angle, and overall width of tibial plateau and widths of medial and lateral tibial plateau were measured before TKA. The tibial component coronal alignment angle (TCCA) was measured after the operation. Malalignment of the tibial prosthesis was defined as TCCA <87° or TCCA >93°. Tibial bowing was indicated by TBA >2°, and lateral bowing was recorded as +. The correlations of TCCA with demographic data and pre-operation imaging measurement parameters were statistically analyzed. Results: Bivariate correlation analysis revealed negative correlations between TCCA and TBA (r = -0.602, P < 0.001) and TPSA (r = -0.304, P < 0.001), and a positive correlation with MPTA (r = -0.318, P < 0.001). Multivariate linear regression analysis demonstrated a significant negative correlation between TCCA and TBA (P < 0.001). The occurrence rate of malalignment of tibial prosthesis was 12.37 %. The occurrence rates of malalignment were 22.54 % in the tibial bowing group and 6.87 % in the non-tibial bowing group, showing statistical differences (P < 0.001). Conclusion: The malalignment rate of tibial prosthesis among Southern Chinese patients is relatively high, possibly attributed to the tibial anatomy anomalies, particularly the tibial bowing. The entry point should be determined based on tibial morphology.

11.
J Oleo Sci ; 73(2): 239-251, 2024.
Article in English | MEDLINE | ID: mdl-38311413

ABSTRACT

Frog oil has been recognized for its nutritional and medicinal value. However, there is limited research on the role of frog oil in preventing obesity. In this study, we aimed to investigate the lipid composition of Quasipaa spinosa oil (QSO) and Rana catesbeiana oil (RCO) using lipidomics analysis. We compared the lipid accumulation effects of these two kinds of frog oils and soybean oil (SO) in Caenorhabditis elegans (C. elegans). Additionally, we determined the gene expression related to lipid metabolism and used the nhr-49 mutant (RB1716) and sir-2.1 mutant (VC199) for validation experiments. The results showed that the lipid composition of QSO and RCO was significantly different (p < 0.05), and QSO was rich in more polyunsaturated fatty acids (PUFAs). After feeding C. elegans, the lipid accumulation of the QSO group was the lowest among the three dietary oil groups. In addition, compared with RCO and SO, QSO significantly inhibited the production of malondialdehyde (MDA) and increased the activity of superoxide dismutase (SOD). The effects of three kinds of dietary oils on the fatty acid composition of C. elegans were significantly different. Compared with SO and RCO, QSO significantly up-regulated (p < 0.05) the expression of sir-2.1 and ech-1 genes. The results showed that QSO might reduce lipid accumulation through the SIRT1 and nuclear hormone signaling pathways. Such a situation was verified experimentally by the nhr-49 mutant (RB1716) and sir-2.1 mutant (VC199). This study proposed a new functional oil, laying the groundwork for developing functional foods from Quasipaa spinosa.


Subject(s)
Caenorhabditis elegans , Dietary Fats, Unsaturated , Animals , Caenorhabditis elegans/genetics , Caenorhabditis elegans/metabolism , Rana catesbeiana/metabolism , Fatty Acids/metabolism , Fatty Acids, Unsaturated/metabolism , Dietary Fats, Unsaturated/pharmacology , Soybean Oil/metabolism , Lipid Metabolism/genetics
12.
Bioorg Med Chem Lett ; 99: 129615, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38199331

ABSTRACT

Monocyclic ß-lactams are stable to a number of ß-lactamases and are the focus of researchers for the development of antibacterial drugs, particularly against Enterobacterales. We recently synthesized and reported the bactericidal activity of diverse series of aztreonam appended with amidine moieties as siderophores. One of the derivatives exhibiting the highest MIC value in vitro was selected for further preclinical studies. The compound DPI-2016 was reassessed for its synthetic routes and methods that were improved to find the maximum final yields aimed at large-scale synthesis. In addition, the results of the pharmacological studies were determined with reference to aztreonam. It has been found that the compound DPI-2016 showed comparable or slightly improved ADMET as well as pharmacokinetic parameters to aztreonam. It is estimated that the compound could be a potential lead for further clinical evaluation.


Subject(s)
Aztreonam , Monobactams , Monobactams/pharmacology , Aztreonam/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , beta-Lactamases , Microbial Sensitivity Tests
13.
J Pediatr ; 267: 113908, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38220065

ABSTRACT

OBJECTIVE: To compare brain magnetic resonance imaging (MRI) biomarkers and neurodevelopmental test scores in infants born preterm with and without prenatal opioid exposure (POE). STUDY DESIGN: We examined 395 preterm infants (≤32 weeks gestational age) who had term-equivalent brain MRIs, composite scores from the Bayley Scales of Infant and Toddler Development-III at 2 years corrected age, and POE data. MRI parameters included total/regional brain volumes and severe punctate white matter lesions (PWMLs). We conducted bivariable analysis and multivariable logistic regression analyses. RESULTS: The mean ± SD gestational age was 29.3 ± 2.5 weeks; 35 (8.9%) had POE and 20 (5.1%) had severe PWML. Compared with unexposed infants, those with POE exhibited higher rates of severe PWML (17.1% vs 3.9%, respectively; P = .002); findings remained significant with an OR of 4.16 (95% CI, 1.26-13.68) after adjusting for confounders. On mediation analysis, the significant relationship between POE and severe PWML was not indirectly mediated through preterm birth/gestational age (OR, 0.93; 95% CI, 0.78-1.10), thus suggesting the association was largely driven by a direct adverse effect of POE on white matter. In multivariable analyses, POE was associated with a significantly lower score by -6.2 (95% CI, -11.8 to -0.6) points on the Bayley Scales of Infant and Toddler Development-III Motor subscale compared with unexposed infants. CONCLUSIONS: POE was associated with severe PWML; this outcome may be a direct effect of POE rather than being mediated by premature birth. POE was also associated with worse motor development. Continued follow-up to understand the long-term effects of POE is warranted.


Subject(s)
Premature Birth , White Matter , Infant , Pregnancy , Female , Infant, Newborn , Humans , Child, Preschool , Infant, Premature , Analgesics, Opioid/adverse effects , Brain/diagnostic imaging , Brain/pathology , White Matter/diagnostic imaging , Gestational Age
14.
Ren Fail ; 46(1): 2300314, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38189082

ABSTRACT

PURPOSE: To investigate the effects of canagliflozin (20 mg/kg) on Dahl salt-sensitive (DSS) rat gut microbiota and salt-sensitive hypertension-induced kidney injury and further explore its possible mechanism. METHODS: Rats were fed a high-salt diet to induce hypertension and kidney injury, and physical and physiological indicators were measured afterwards. This study employed 16S rRNA sequencing technology and liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based metabolic profiling combined with advanced differential and association analyses to investigate the correlation between the microbiome and the metabolome in male DSS rats. RESULTS: A high-salt diet disrupted the balance of the intestinal flora and increased toxic metabolites (methyhistidines, creatinine, homocitrulline, and indoxyl sulfate), resulting in severe kidney damage. Canagliflozin contributed to reconstructing the intestinal flora of DSS rats by significantly increasing the abundance of Corynebacterium spp., Bifidobacterium spp., Facklamia spp., Lactobacillus spp., Ruminococcus spp., Blautia spp., Coprococcus spp., and Allobaculum spp. Moreover, the reconstruction of the intestinal microbiota led to significant changes in host amino acid metabolite concentrations. The concentration of uremic toxins, such as methyhistidines, creatinine, and homocitrulline, in the serum of rats was decreased by canagliflozin, which resulted in oxidative stress and renal injury alleviation. CONCLUSION: Canagliflozin may change the production of metabolites and reduce the level of uremic toxins in the blood circulation by reconstructing the intestinal flora of DSS rats fed a high-salt diet, ultimately alleviating oxidative stress and renal injury.


Subject(s)
Gastrointestinal Microbiome , Hypertension , Toxins, Biological , Male , Animals , Rats , Canagliflozin/pharmacology , Canagliflozin/therapeutic use , Rats, Inbred Dahl , Uremic Toxins , Chromatography, Liquid , Creatinine , RNA, Ribosomal, 16S , Tandem Mass Spectrometry , Sodium Chloride , Diet , Kidney
15.
AJR Am J Roentgenol ; 222(1): e2329812, 2024 01.
Article in English | MEDLINE | ID: mdl-37530398

ABSTRACT

BACKGROUND. Radiologists have variable diagnostic performance and considerable interreader variability when interpreting MR enterography (MRE) examinations for suspected Crohn disease (CD). OBJECTIVE. The purposes of this study were to develop a machine learning method for predicting ileal CD by use of radiomic features of ileal wall and mesenteric fat from noncontrast T2-weighted MRI and to compare the performance of the method with that of expert radiologists. METHODS. This single-institution study included retrospectively identified patients who underwent MRE for suspected ileal CD from January 1, 2020, to January 31, 2021, and prospectively enrolled participants (patients with newly diagnosed ileal CD or healthy control participants) from December 2018 to October 2021. Using axial T2-weighted SSFSE images, a radiologist selected two slices showing greatest terminal ileal wall thickening. Four ROIs were segmented, and radiomic features were extracted from each ROI. After feature selection, support-vector machine models were trained to classify the presence of ileal CD. Three fellowship-trained pediatric abdominal radiologists independently classified the presence of ileal CD on SSFSE images. The reference standard was clinical diagnosis of ileal CD based on endoscopy and biopsy results. Radiomic-only, clinical-only, and radiomic-clinical ensemble models were trained and evaluated by nested cross-validation. RESULTS. The study included 135 participants (67 female, 68 male; mean age, 15.2 ± 3.2 years); 70 were diagnosed with ileal CD. The three radiologists had accuracies of 83.7% (113/135), 88.1% (119/135), and 86.7% (117/135) for diagnosing CD; consensus accuracy was 88.1%. Interradiologist agreement was substantial (κ = 0.78). The best-performing ROI was bowel core (AUC, 0.95; accuracy, 89.6%); other ROIs had worse performance (whole-bowel AUC, 0.86; fat-core AUC, 0.70; whole-fat AUC, 0.73). For the clinical-only model, AUC was 0.85 and accuracy was 80.0%. The ensemble model combining bowel-core radiomic and clinical models had AUC of 0.98 and accuracy of 93.5%. The bowel-core radiomic-only model had significantly greater accuracy than radiologist 1 (p = .009) and radiologist 2 (p = .02) but not radiologist 3 (p > .99) or the radiologists in consensus (p = .05). The ensemble model had greater accuracy than the radiologists in consensus (p = .02). CONCLUSION. A radiomic machine learning model predicted CD diagnosis with better performance than two of three expert radiologists. Model performance improved when radiomic data were ensembled with clinical data. CLINICAL IMPACT. Deployment of a radiomic-based model including T2-weighted MRI data could decrease interradiologist variability and increase diagnostic accuracy for pediatric CD.


Subject(s)
Crohn Disease , Ileal Diseases , Child , Humans , Male , Female , Adolescent , Magnetic Resonance Imaging/methods , Retrospective Studies , Radiomics , Machine Learning
16.
Int J Biol Macromol ; 254(Pt 3): 128028, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37952806

ABSTRACT

Oligosaccharide-containing macromolecular bio adhesives are emerging as highly promising eco-friendly materials to enhance the cytocompatibility of viscous hydrogels for wound healing applications. In our prior research, we extensively elucidated the properties of branch-structure fructo-oligosaccharides derived from Polygonatum Cyrtonema Hua (referred to as PCOS). However, the characteristics of hydrogels based on fructo-oligosaccharides remain to be fully explored. In present work, we developed an injectable, PCOS/carboxymethyl cellulose (CMC) hydrogel which is a dual ion-physical cross-linked hydrogel that can be considered as a potential diabetic wound dressing. The tests showed that the optimal ratios for hydrogel preparation were 2 % CBM 940 (Carbomer 940), 5 % CMC and 10 % PCOS. The resultant hydrogel was formulated into composite hydrogels that were then used for the treatment of full-thickness excisional wounds in a db/db diabetic mouse model. Wound closure and histological evaluation confirmed its beneficial effect on wound healing. Further morphological analysis through scanning electron microscopy images revealed a porous hydrogel structure, while Fourier-transform infrared spectroscopy provided structural insights on the crosslinking reaction. Physicochemical properties of the hybrid hydrogels determined by rheological properties, thermogravimetric, water loss rate, et al., indicated that the double crosslinking PCOS/CMC hybrid hydrogel showed enhanced dynamic mechanical properties and water retention capacity compared to the CMC cellulose matrix hydrogels. Thus, this novel PCOS-hybrid hydrogel exhibited good dissolvability and injectable properties, which was proved to facilitate for the diabetic wound healing both in vitro and in vivo test and holds a potential clinical application in the wound healing.


Subject(s)
Diabetes Mellitus , Polycystic Ovary Syndrome , Polygonatum , Humans , Mice , Animals , Female , Hydrogels/chemistry , Cellulose/pharmacology , Cellulose/chemistry , Polycystic Ovary Syndrome/drug therapy , Oligosaccharides , Diabetes Mellitus/drug therapy , Water , Anti-Bacterial Agents/therapeutic use
17.
J Sci Food Agric ; 104(5): 2630-2640, 2024 Mar 30.
Article in English | MEDLINE | ID: mdl-37985216

ABSTRACT

BACKGROUND: Understanding the role of adjuvants in pesticide persistence is crucial to develop effective pesticide formulations and manage pesticide residues in fresh produce. This study investigated the impact of a commercial non-ionic surfactant product containing alkylphenol ethoxylates (APEOs) on the persistence of thiabendazole on apple and spinach surfaces against the 30 kg m-3 baking soda (sodium bicarbonate, NaHCO3 ) soaking, which was used to remove the active ingredient (AI) in the cuticular wax layer of fresh produce through alkaline hydrolysis. Surface-enhanced Raman scattering (SERS) mapping method was used to quantify the residue levels on fresh produce surfaces at different experimental scenarios. Four standard curves were established to quantify surface thiabendazole in the absence and presence of APEOs, on apple and spinach leaf surfaces, respectively. RESULTS: Overall, the result showed that APEOs enhanced the persistence of thiabendazole over time. After 3 days of exposure, APEOs increased thiabendazole surface residue against NaHCO3 hydrolysis on apple and spinach surfaces by 5.39% and 10.47%, respectively. CONCLUSION: The study suggests that APEOs led to more pesticide residues on fresh produce and greater difficulty in washing them off from the surfaces using baking soda, posing food safety concerns. © 2023 Society of Chemical Industry.


Subject(s)
Malus , Pesticide Residues , Pesticides , Malus/chemistry , Pesticide Residues/analysis , Pesticides/analysis , Sodium Bicarbonate , Spectrum Analysis, Raman/methods , Spinacia oleracea/chemistry , Surface-Active Agents , Thiabendazole/analysis , Phenols/chemistry
18.
Virol J ; 20(1): 254, 2023 11 02.
Article in English | MEDLINE | ID: mdl-37919730

ABSTRACT

PURPOSE: To investigate the distribution of the incidence and genotypes of human papillomavirus (HPV) among women with cervical cancer (CC) and precancerous cervical lesions in Yueyang City, China, to develop prevention and control strategies for CC. METHODS: A total of 3674 patients with cervical lesions and cervical cancer who attended 7 hospitals in Yueyang City between September 2019 and September 2022 were included. They included 1910 cervical intraepithelial neoplasia (CIN) I, 718 CIN II, 576 CIN II and 470 CC, respectively. The HPV genotyping of the above patients was detected by Real time-PCR in the laboratory department of each hospital. RESULTS: The total HPV prevalence was 74.69% (95% CI 73.28-76.09%) in 3674 patients. The incidence of high- and low-risk HPV was 73.46% and 7.21%, respectively. The prevalence of HPV in CIN I, CIN II, CIN III, and invasive CC (ICC) groups was 66.65% (1273/1910, 95% CI 64.53-68.77%), 80.78% (580/718, 95% CI 77.89-83.67%), 83.88% (483/576, 95% CI 80.84-86.87%), and 86.81% (408/470, 95% CI 83.74-89.88%), respectively. The top three HPV subtypes in ICC are HPV16, HPV52, and HPV58. The prevalence of HPV 16 increased with increasing disease severity, with this genotype being present in 12.57%, 20.89%, 36.98%, and 50.85% of CIN I, CIN II, CIN III, and ICC cases, respectively (p < 0.001). Single HPV infection was predominant in cervical lesions, with a prevalence of 48.50% (95% CI 46.89-50.12%). The HPV prevalence varied by age, being highest among women with ICC, CIN I, CIN II and CIN III aged ≥ 60 years, 50-59 years, 40-49 years, and 40-49 years, respectively. CONCLUSION: The prevalence of HPV in patients with cervical lesions in Yueyang City was very high, with HPV 16, 52, 58, 53, and 51 being the five most common HPV genotypes in patients with cervical lesions.


Subject(s)
Papillomavirus Infections , Precancerous Conditions , Uterine Cervical Dysplasia , Uterine Cervical Neoplasms , Humans , Female , Middle Aged , Papillomavirus Infections/complications , Papillomavirus Infections/epidemiology , Human Papillomavirus Viruses , Cross-Sectional Studies , Papillomaviridae/genetics , China/epidemiology , Human papillomavirus 16/genetics , Genotype , Prevalence
19.
Protein Pept Lett ; 30(12): 992-1000, 2023.
Article in English | MEDLINE | ID: mdl-38013437

ABSTRACT

OBJECTIVES: We aim to investigate the regulatory mechanisms of miR-455-5p/SOCS3 pathway that underlie the proliferation, migration, and invasion of triple-negative breast cancer (TNBC) cells. METHODS: Reverse transcription-quantitative PCR (RT-qPCR) was used to detect miR-455-5p expression in breast cancer tissues and cell lines. CCK8 and Transwell assays were conducted to assess the effects of miR-455-5p on breast cancer line proliferation, migration, and invasion. SOCS3 expression level in breast cancer tissues and cell lines was determined by qPCR and western blotting. The targeting relationship between miR-455-5p and SOCS3 was determined by dual luciferase reporter gene assay in different breast cancer cell lines. Finally, the upstream and downstream regulatory association between miR-455-5p and SOCS3 was confirmed in breast cancer cells by CCK8, western blot, and Transwell assays. RESULTS: MiR-455-5p expression was up-regulated in breast cancer tissues; miR-455-5p regulates TNBC proliferation, migration, and invasion of TNBC. SOCS3 was the direct target of miR-455-5p and was down-regulated in breast cancer. Interference with SOCS3 reversed the inhibitory effect of the miR-455-5p inhibitor on breast cancer cells' malignant potential. CONCLUSION: MiR-455-5p promotes breast cancer progression by targeting the SOCS3 pathway and may be a potential therapeutic target for breast cancer.


Subject(s)
MicroRNAs , Triple Negative Breast Neoplasms , Humans , MicroRNAs/genetics , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/metabolism , Triple Negative Breast Neoplasms/pathology , Cell Line, Tumor , Cell Proliferation/genetics , MCF-7 Cells , Cell Movement/genetics , Gene Expression Regulation, Neoplastic , Suppressor of Cytokine Signaling 3 Protein/genetics , Suppressor of Cytokine Signaling 3 Protein/metabolism
20.
J Int Med Res ; 51(10): 3000605231206289, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37862678

ABSTRACT

OBJECTIVES: This study assessed the antifibrotic effects of canagliflozin, with or without irbesartan, on renal injury in Dahl salt-sensitive (SS) rats fed a high-salt (HS) diet. METHODS: After the preconditioning stage, Dahl SS rats (n = 47) were divided into five experimental groups as follows: low-salt (LS, n = 7), HS (n = 10), HS with canagliflozin (n = 10), HS with irbesartan (n = 10), and HS with canagliflozin and irbesartan (n = 10). RESULTS: The HS diet increased systolic blood pressure (SBP), renal fibrosis, fibrotic protein expression, and transforming growth factor-ß1 (TGF-ß1)/Smad2/3 pathway protein expression compared with the findings in the LS group. Irbesartan reduced SBP and slowed the loss of renal function. Canagliflozin significantly reduced body weight and renal fibrosis and suppressed the TGF-ß1/Smad2/3 pathway. The combined therapy exerted better renoprotective effects on all outcome parameters. CONCLUSIONS: These results indicate that canagliflozin and irbesartan exert different effects on renal injury in SS hypertensive rats, and the combined regimen could have stronger effects than either monotherapy.


Subject(s)
Hypertension , Kidney Diseases , Animals , Rats , Transforming Growth Factor beta1/genetics , Irbesartan/pharmacology , Canagliflozin/pharmacology , Canagliflozin/therapeutic use , Rats, Inbred Dahl , Kidney Diseases/pathology , Kidney/pathology , Hypertension/metabolism , Sodium Chloride , Sodium Chloride, Dietary/pharmacology , Signal Transduction , Fibrosis , Blood Pressure
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