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1.
Front Pharmacol ; 15: 1360179, 2024.
Article in English | MEDLINE | ID: mdl-38803440

ABSTRACT

Diabetic kidney disease (DKD) is one of the chronic microvascular complications caused by diabetes, which is characterized by persistent albuminuria and/or progressive decline of estimated glomerular filtration rate (eGFR), and has been the major cause of dialysis around the world. At present, although the treatments for DKD including lifestyle modification, glycemic control and even using of Sodium-glucose cotransporter 2 (SGLT2) inhibitors can relieve kidney damage caused to a certain extent, there is still a lack of effective treatment schemes that can prevent DKD progressing to ESRD. It is urgent to find new complementary and effective therapeutic agents. Growing animal researches have shown that mitophagy makes a great difference to the pathogenesis of DKD, therefore, exploration of new drugs that target the restoration of mitophagy maybe a potential perspective treatment for DKD. The use of Chinese botanical drugs (CBD) has been identified to be an effective treatment option for DKD. There is growing concern on the molecular mechanism of CBD for treatment of DKD by regulating mitophagy. In this review, we highlight the current findings regarding the function of mitophagy in the pathological damages and progression of DKD and summarize the contributions of CBD that ameliorate renal injuries in DKD by interfering with mitophagy, which will help us further explain the mechanism of CBD in treatment for DKD and explore potential therapeutic strategies for DKD.

2.
BMC Med Imaging ; 24(1): 126, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38807064

ABSTRACT

BACKGROUND: Automated Breast Ultrasound (AB US) has shown good application value and prospects in breast disease screening and diagnosis. The aim of the study was to explore the ability of AB US to detect and diagnose mammographically Breast Imaging Reporting and Data System (BI-RADS) category 4 microcalcifications. METHODS: 575 pathologically confirmed mammographically BI-RADS category 4 microcalcifications from January 2017 to June 2021 were included. All patients also completed AB US examinations. Based on the final pathological results, analyzed and summarized the AB US image features, and compared the evaluation results with mammography, to explore the detection and diagnostic ability of AB US for these suspicious microcalcifications. RESULTS: 250 were finally confirmed as malignant and 325 were benign. Mammographic findings including microcalcifications morphology (61/80 with amorphous, coarse heterogeneous and fine pleomorphic, 13/14 with fine-linear or branching), calcification distribution (189/346 with grouped, 40/67 with linear and segmental), associated features (70/96 with asymmetric shadow), higher BI-RADS category with 4B (88/120) and 4 C (73/38) showed higher incidence in malignant lesions, and were the independent factors associated with malignant microcalcifications. 477 (477/575, 83.0%) microcalcifications were detected by AB US, including 223 malignant and 254 benign, with a significantly higher detection rate for malignant lesions (x2 = 12.20, P < 0.001). Logistic regression analysis showed microcalcifications with architectural distortion (odds ratio [OR] = 0.30, P = 0.014), with amorphous, coarse heterogeneous and fine pleomorphic morphology (OR = 3.15, P = 0.037), grouped (OR = 1.90, P = 0.017), liner and segmental distribution (OR = 8.93, P = 0.004) were the independent factors which could affect the detectability of AB US for microcalcifications. In AB US, malignant calcification was more frequent in a mass (104/154) or intraductal (20/32), and with ductal changes (30/41) or architectural distortion (58/68), especially with the both (12/12). BI-RADS category results also showed that AB US had higher sensitivity to malignant calcification than mammography (64.8% vs. 46.8%). CONCLUSIONS: AB US has good detectability for mammographically BI-RADS category 4 microcalcifications, especially for malignant lesions. Malignant calcification is more common in a mass and intraductal in AB US, and tend to associated with architectural distortion or duct changes. Also, AB US has higher sensitivity than mammography to malignant microcalcification, which is expected to become an effective supplementary examination method for breast microcalcifications, especially in dense breasts.


Subject(s)
Breast Neoplasms , Calcinosis , Ultrasonography, Mammary , Humans , Calcinosis/diagnostic imaging , Female , Retrospective Studies , Middle Aged , Ultrasonography, Mammary/methods , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/pathology , Adult , Aged , Mammography/methods , Aged, 80 and over
3.
Bioorg Chem ; 148: 107494, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38797067

ABSTRACT

Near-infrared (NIR) responsive nanoparticles are an important platform for multimodal phototherapy. Importantly, the simultaneous NIR-triggered photodynamic (PDT) and photothermal (PTT) therapy is a powerful approach to increase the antitumor efficiency of phototherapic nanoparticles due to the synergistic effect. Herein, a boron dipyrromethene (BODIPY)-based amphiphilic dye with enhanced electron donor-acceptor-donor (D-A-D) structure (BDP-AP) was designed and synthesized, which could self-assemble into stable nanoparticles (BDP-AP NPs) for the synergistic NIR-triggered PDT/PTT therapy. BDP-AP NPs synchronously generated singlet oxygen (1O2) and achieved preeminent photothermal conversion efficiency (61.42%). The in vitro and in vivo experiments showed that BDP-AP NPs possessed negligible dark cytotoxicity and infusive anticancer performance. BDP-AP NPs provide valuable guidance for the construction of PDT/PTT-synergistic NIR nanoagents to improve the efficiency of photoinduced cancer therapy in the future.

4.
J Mol Model ; 30(6): 189, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38801605

ABSTRACT

CONTEXT: In order to further improve the manufacturing technology of resonator facet of GaAs (gallium arsenide)-based laser, the scratching process of GaAs was simulated by molecular dynamics. Models of GaAs crystals with different orientations, including GaAs [100], GaAs [110], and GaAs [111], were generated, followed by scratch simulations on these models. The surface characteristics of scratches, damage width, subsurface damage, stack height, and the distribution and activity characteristics of dislocations were analyzed based on the simulation results. The results show that there are obvious anisotropy in the deformation of different crystal orientation during the scratching process of GaAs. Surface features, damage width, subsurface damage, and dislocation dynamics during scraping in GaAs crystals strongly depend on crystal orientation. It was also observed that GaAs exhibits distinct characteristics of dislocation activity during the scratching process, depending on its crystal orientation. In addition, GaAs [110] crystal direction has the smallest maximum damage width and subsurface damage depth. The maximum of maximum damage width is in GaAs [100] crystal direction, and the maximum subsurface damage depth is in GaAs [111] crystal direction. In addition, the stacking height is maximum when GaAs [100] is scraped and minimum when GaAs [110] is scraped. METHODS: The engraving quality of GaAs materials was investigated utilizing the LAMMPS software through molecular dynamics simulations, while observations were facilitated using the OVITO software. The MD simulation was conducted employing the NPT ensemble, with the temperature fixed at 300 K. A time step of 2 fs was utilized, and the total duration of the MD simulation spanned 600 ps.

5.
Clin Transl Radiat Oncol ; 47: 100792, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38779524

ABSTRACT

Radiation therapy (RT) nowadays is a main treatment modality of cancer. To ensure the therapeutic efficacy of patients, accurate dose distribution is often required, which is a time-consuming and labor-intensive process. In addition, due to the differences in knowledge and experience among participants and diverse institutions, the predicted dose are often inconsistent. In last several decades, artificial intelligence (AI) has been applied in various aspects of RT, several products have been implemented in clinical practice and confirmed superiority. In this paper, we will review the research of AI in dose prediction, focusing on the progress in deep learning (DL).

6.
J Prosthet Dent ; 2024 May 22.
Article in English | MEDLINE | ID: mdl-38782607

ABSTRACT

A 6-year-old child with nonsyndromic oligodontia in the mixed dentition received a removable dental prosthesis with a polyetheretherketone framework and artificial gingiva, restoring esthetics and function. Computer-aided design and computer-aided manufacturing hemispherical glass-ceramic attachments were added to the teeth under the guidance of acid-etching and bonding guides to obtain an undercut area. The bonding and cementation of the attachments and the prosthesis delivery were completed in a single visit. This method offers a suitable prosthodontic treatment option for treating children with oligodontia in the mixed dentition.

7.
Cell Signal ; 120: 111190, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38670474

ABSTRACT

Chronic obstructive pulmonary disease (COPD) is potentially fatal, and as society ages, its effects on human health are predicted to deteriorate. The potential function of m6A modifications within COPD has become a hot topic recently. This study was conducted to clarify the function and related mechanisms of the m6A methylation transferase ZC3H13 in COPD. The expression of m6A-associated protease and ITGA6 in COPD tissues was assessed using GEO data, qRT-PCR, and western blot. COPD models in cells and mice were established through cigarette smoke extract (CSE) and smoke exposure. Inflammatory marker levels were measured by ELISA, apoptosis by flow cytometry, and mRNA stability with Actinomycin D assay. m6A modification levels were checked by MeRIP-PCR. HE and Masson staining evaluated lung pathology, and alveolar lavage fluid analysis included total cell count and Giemsa staining. ZC3H13 and METTL3 were differentially expressed m6A regulators in COPD, with ZC3H13 being more significantly upregulated. Further analysis revealed the ZC3H13 expression-related differentially expressed genes (DEGs) functions were enriched in the immunoinflammatory pathway, indicating ZC3H13's involvement in COPD pathogenesis through inflammation, and immune responses. Knockdown studies in cellular and mouse models demonstrated ZC3H13's role in exacerbating COPD symptoms, including inflammation, apoptosis, and EMT, and its suppression led to significant improvements. The identification of ITGA6 as a target gene further elucidated the mechanism, showing that ZC3H13 enhances ITGA6 expression and mRNA stability through m6A modification, influencing bronchial epithelial cell inflammation and fibrosis. In conclusion, targeting ZC3H13/ITGA6 could be an underlying therapeutic approach for treating COPD.

8.
Food Funct ; 15(10): 5352-5363, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38635214

ABSTRACT

Human milk represents the gold standard for infant nutrition, with approximately 50% of the energy in human milk derived from lipids. Odd-chain fatty acids (OCFAs) have been recognized as a category of bioactive milk fatty acids in recent research; however, limited data exist on OCFAs in human milk. This study collected human milk samples spanning the postpartum period from 0 to 400 days. Phospholipids containing OCFAs (PL-OCFAs) were determined in 486 human milk samples using hydrophilic liquid chromatography-electrospray ionization-triquadrupole-mass spectrometry. Triacylglycerols containing OCFAs (TAG-OCFAs) were analyzed in 296 human milk samples using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The average total concentration of PL-OCFA ranged from 30.89 ± 14.27 mg L-1 to 93.48 ± 36.55 mg L-1 during lactation, and the average total TAG-OCFA content ranged from 103.1 ± 147.15 mg L-1 to 965.41 ± 651.67 mg L-1. Despite the lower absolute concentration of PL-OCFA, its relative concentration (8.75%-11.75%) was significantly higher than that of TAG-OCFA (0.37%-1.85%) throughout lactation. PC-OCFA, SM-OCFA and PE-OCFA are major sub-classes of PL-OCFA. Furthermore, C17:0 was the major chain length in both PL-OCFA and TAG-OCFA, followed by C15:0. C17:1 was characteristic of TAG-OCFA, while long-chain fatty acids C19:0, C21:0 and C23:0 were characteristic of PL-OCFA. Our findings highlighted the importance of bioactive lipids in human milk, suggesting that OCFAs could be targeted in future studies in relation to the health and development of infants.


Subject(s)
Fatty Acids , Lactation , Milk, Human , Phospholipids , Triglycerides , Humans , Milk, Human/chemistry , Female , Phospholipids/analysis , Phospholipids/chemistry , Triglycerides/chemistry , Fatty Acids/analysis , Fatty Acids/chemistry , China , Adult , East Asian People
9.
Mar Environ Res ; 198: 106496, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38640691

ABSTRACT

The carbonate chemistry in river-dominated marginal seas is highly heterogeneous, and there is ongoing debate regarding the definition of atmospheric CO2 source or sink. On this basis, we investigated the carbonate chemistry and air-sea CO2 fluxes in a hotspot estuarine area: the Changjiang Estuary during winter and summer. The spatial characteristics of the carbonate system were influenced by water mixing of three end-members in winter, including the Changjiang freshwater with low total alkalinity (TA) concentration, the less saline Yellow Sea Surface Water with high TA, and the saline East China Sea (ECS) offshore water with moderate TA. While in summer with increased river discharge, the carbonate system was regulated by simplified two end-member mixing between the Changjiang freshwater and the ECS offshore water. By performing the end-member mixing model on DIC variations in the river plume region, significant biological addition of DIC was found in winter with an estimation of -120 ± 113 µmol kg-1 caused by wintertime organic matter remineralization from terrestrial source. While this biological addition of DIC shifted to DIC removal due to biological production in summer supported by the increased nutrient loading from Changjiang River. The pCO2 dynamics in the river plume and the ECS offshore were both subjected to physical mixing of freshwater and seawater, whether in winter and summer. In the inner estuary without horizontal mixing, the pCO2 dynamics were mainly influenced by biological uptake in winter and temperature in summer. The inner estuary, the river plume, and the ECS offshore were sources of atmospheric CO2, with their contributions varying seasonally. The Changjiang runoff enhanced the inner estuary's role as a CO2 source in summer, while intensive biological uptake reduced the river plume's contribution.

10.
Adv Mater ; : e2312219, 2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38608672

ABSTRACT

Targeting the competitive-cooperative relationships among tumor cells and various immune cells can efficiently reverse the immune-dysfunction microenvironment to boost the immunotherapies for the triple-negative breast cancer treatment. Hence, a bacterial outer membrane vesicle-based nanocomplex is designed for specifically targeting malignant cells and immune cells to reconcile the relationships based on metabolic-immune crosstalk. By uniquely utilizing the property of charge-reversal polymers to realize function separation, the nanocomplexes could synergistically regulate tumor cells and immune cells. This approach could reshape the immunosuppressive competition-cooperation pattern into one that is immune-responsive, showcasing significant potential for inducing tumor remission in TNBC models.

11.
Cryst Growth Des ; 24(8): 3277-3288, 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38659658

ABSTRACT

Precision measurement of the growth rate of individual single crystal facets (hkl) represents an important component in the design of industrial crystallization processes. Current approaches for crystal growth measurement using optical microscopy are labor intensive and prone to error. An automated process using state-of-the-art computer vision and machine learning to segment and measure the crystal images is presented. The accuracies and efficiencies of the new crystal sizing approach are evaluated against existing manual and semi-automatic methods, demonstrating equivalent accuracy but over a much shorter time, thereby enabling a more complete kinematic analysis of the overall crystallization process. This is applied to measure in situ the crystal growth rates and through this determining the associated kinetic mechanisms for the crystallization of ß-form l-glutamic acid from the solution phase. Growth on the {101} capping faces is consistent with a Birth and Spread mechanism, in agreement with the literature, while the growth rate of the {021} prismatic faces, previously not available in the literature, is consistent with a Burton-Cabrera-Frank screw dislocation mechanism. At a typical supersaturation of σ = 0.78, the growth rate of the {101} capping faces (3.2 × 10-8 m s-1) is found to be 17 times that of the {021} prismatic faces (1.9 × 10-9 m s-1). Both capping and prismatic faces are found to have dead zones in their growth kinetic profiles, with the capping faces (σc = 0.23) being about half that of the prismatic faces (σc = 0.46). The importance of this overall approach as an integral component of the digital design of industrial crystallization processes is highlighted.

12.
Orthod Craniofac Res ; 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38558502

ABSTRACT

INTRODUCTION: The purpose of this study was to evaluate the therapeutic effect of modified clear Twin Block (CTB) aligner and traditional twin block (TB) appliance from skeletal, dentoalveolar and soft tissue changes in adolescents with skeletal class II malocclusion. METHODS: A total of 80 adolescents, included in this study from two medical centres, were distributed into CTB group, TB group and control group based on the treatment they received. Lateral cephalograms at pre-treatment (T1) and post-treatment (T2) were measured by modified Pancherz's cephalometric analysis, and dentoskeletal and soft tissue changes were analysed by independent-sample t-test, paired-sample t-test, ANOVA test and Scheffe's Post Hoc test. RESULTS: Seventy-five adolescents completed the study, including 32 in the CTB group, 32 in the TB group and 11 in the control group. Both CTB and TB treatment showed significant differences in most dentoskeletal and soft tissue measurements. Compared with the control group, improvements were observed in class II molar relationship through significant different in S Vert/Ms-S Vert/Mi in the CTB group (P < .01) and the TB group (P < .001), as well as deep overjet through significant different in S Vert/Is-S Vert/Ii in the CTB group (P < .001) and the TB group (P < .001). Besides, the CTB group also showed less protrusion of lower incisors and resulted in a more significant improvement in profile with fewer adverse effects on speaking, eating and social activities. CONCLUSIONS: For adolescents with skeletal class II malocclusion, CTB appliance was as effective as TB on improving dentoskeletal and soft tissue measurements, featuring more reliable teeth control and patient acceptance.

14.
Pharmacogenomics J ; 24(2): 6, 2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38438359

ABSTRACT

The objective of this study was to discover clinical and pharmacogenetic factors associated with bevacizumab-related gastrointestinal hemorrhage in Cancer and Leukemia Group B (Alliance) 90401. Patients with metastatic castration-resistant prostate cancer received docetaxel and prednisone ± bevacizumab. Patients were genotyped using Illumina HumanHap610-Quad and assessed using cause-specific risk for association between single nucleotide polymorphisms (SNPs) and gastrointestinal hemorrhage. In 1008 patients, grade 2 or higher gastrointestinal hemorrhage occurred in 9.5% and 3.8% of bevacizumab (n = 503) and placebo (n = 505) treated patients, respectively. Bevacizumab (P < 0.001) and age (P = 0.002) were associated with gastrointestinal hemorrhage. In 616 genetically estimated Europeans (n = 314 bevacizumab and n = 302 placebo treated patients), grade 2 or higher gastrointestinal hemorrhage occurred in 9.6% and 2.0% of patients, respectively. One SNP (rs1478947; HR 6.26; 95% CI 3.19-12.28; P = 9.40 × 10-8) surpassed Bonferroni-corrected significance. Grade 2 or higher gastrointestinal hemorrhage rate was 33.3% and 6.2% in bevacizumab-treated patients with the AA/AG and GG genotypes, versus 2.9% and 1.9% in the placebo arm, respectively. Prospective validation of these findings and functional analyses are needed to better understand the genetic contribution to treatment-related gastrointestinal hemorrhage.


Subject(s)
Pharmacogenetics , Prostatic Neoplasms , Male , Humans , Bevacizumab/adverse effects , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/genetics , Gastrointestinal Hemorrhage/chemically induced , Gastrointestinal Hemorrhage/genetics , Risk Factors
15.
Adv Sci (Weinh) ; 11(20): e2307319, 2024 May.
Article in English | MEDLINE | ID: mdl-38502885

ABSTRACT

The senescence of aortic valve interstitial cells (VICs) plays a critical role in the progression of calcific aortic valve disease (CAVD). However, the precise mechanisms underlying the senescence of VICs remain unclear, demanding the identification of a novel target to mitigate this process. Previous studies have highlighted the anti-aging potential of morusin. Thus, this study aimed to explore the therapeutic potential of morusin in CAVD. Cellular experiments reveal that morusin effectively suppresses cellular senescence and cause a shift toward osteogenic differentiation of VICs in vitro. Mechanistically, morusin activate the Nrf2-mediated antiaging signaling pathway by downregulating CCND1 expression and aiding Keap1 degradation through Trim 25. This activation lead to the upregulated expression of antioxidant genes, thus reducing reactive oxygen species production and thereby preventing VIC osteogenic differentiation. In vivo experiments in ApoE-/- mice on a high-fat Western diet demonstrate the positive effect of morusin in mitigating aortic valve calcification. These findings emphasize the antiaging properties of morusin and its potential as a therapeutic agent for CAVD.


Subject(s)
Aortic Valve Stenosis , Aortic Valve , Calcinosis , Cellular Senescence , NF-E2-Related Factor 2 , Signal Transduction , Animals , Aortic Valve/metabolism , Aortic Valve/pathology , Mice , Cellular Senescence/drug effects , NF-E2-Related Factor 2/metabolism , NF-E2-Related Factor 2/genetics , Calcinosis/metabolism , Calcinosis/genetics , Signal Transduction/drug effects , Aortic Valve Stenosis/metabolism , Aortic Valve Stenosis/genetics , Aortic Valve Stenosis/pathology , Disease Models, Animal , Cyclin D1/metabolism , Cyclin D1/genetics , Male , Transcription Factors/metabolism , Transcription Factors/genetics , Osteogenesis/drug effects , Humans , Mice, Inbred C57BL
16.
Health Sci Rep ; 7(2): e1903, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38410499

ABSTRACT

Background and Aims: The prevalence of gestational diabetes mellitus (GDM) continues to increase, and the phenomenon of women giving birth at an older age is becoming more common worldwide. Less is known abouts the impact of GDM combined with advanced maternal age (AMA) on pregnancy outcomes. To explore the impact of AMA complicated with GDM on pregnancy outcomes. Methods: This study included 34,602 pregnancies between 2018 and 2020 in Hangzhou, China. The pregnant women were divided into four groups according to advanced age (≥35 years) and GDM as follows: AMA women without GDM (non-AGDM) group (n = 2614), young pregnant women with GDM (YGDM) group (n = 4016), AMA women with GDM (AGDM) group (n = 850), and young pregnant women without GDM (non-YGDM) group (n = 27,122). Univariate analysis was carried out by Mann-Whitney U test or Pearson's χ 2 test. Multivariate logistic regression analysis was used to investigate the effect of AMA and GDM on pregnancy outcomes. Results: Multivariate logistic regression analysis showed that in the comparison against non-YGDM garoup, the ORs of fetal chromosome abnormality, parity, urgent cesarean section, gravidity, scheduled cesarean section, body mass index (BMI) ≥30 kg/m2, pre-eclampsia, thrombocytopenia, hyperlipidemia, BMI 25-29.9 kg/m2, blood urea nitrogen, fasting blood glucose, and creatinine in AGDM group were 16.044, 4.284, 3.530, 3.284, 3.257, 2.049, 1.935, 1.898, 1.690, 1.471, 1.304, 1.216, and 1.026 (all p < 0.05). Conclusions: The prevalence of pregnant women with AGDM was 2.46% in Hang Zhou, China. The increasing gravidity of AMA women was related to a greater risk of GDM. The AGDM group associated with a greater risks of chromosomal abnormality in offspring and cesarean section, especially urgent cesarean section.

17.
Mar Pollut Bull ; 200: 116095, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38325205

ABSTRACT

An integrated observation of NOx that included coastal cities and oceanic cruises covering the Qingdao coastal waters sites (QDCW) and the Yellow Sea and East China Sea sites (YECS) was conducted in spring. The average concentrations of the coastal cities, the QDCW, and the YECS were 5.4 ± 4.1, 4.2 ± 3.5, and 2.9 ± 6.8 ppb for NO while 18.5 ± 7.2, 9.4 ± 5.2, and 4.9 ± 6.4 ppb for NO2, depicting lowest levels in the open seas. Atmospheric NO and NO2 showed similar spatial variations over the seas, the stations where the air masses originated from land or nearshore regions showed higher levels, but the decisive influencing factors were not the same in the different study areas. The calculated NOx flux value in the YECS (-8.7 × 10-17 mol N cm-2) indicated that the sea surface was a net sink of atmospheric NOx.


Subject(s)
Air Pollutants , Seawater , Air Pollutants/analysis , Nitrogen Dioxide , Environmental Monitoring , Oceans and Seas , Nitrogen Oxides , China
18.
Int J Ophthalmol ; 17(2): 282-288, 2024.
Article in English | MEDLINE | ID: mdl-38371261

ABSTRACT

AIM: To define the predictive factors of severe retinopathy of prematurity (ROP) and develop a nomogram for predicting severe ROP in southeast China. METHODS: Totally 554 infants diagnosed with ROP hospitalized in the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University and hospitalized in Taizhou Women and Children's Hospital were included. Clinical data and 43 candidate predictive factors of ROP infants were collected retrospectively. Logistic regression model was used to identify predictive factors of severe ROP and to propose a nomogram for individual risk prediction, which was compared with WINROP model and Digirop-Birth model. RESULTS: Infants from the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University (n=478) were randomly allocated into training (n=402) and internal validation group (n=76). Infants from Taizhou Women and Children's Hospital were set as external validation group (n=76). Severe ROP were found in 52 of 402 infants, 12 of 76 infants, and 7 of 76 infants in training group, internal validation group, and external validation group, respectively. Birth weight [odds ratio (OR), 0.997; 95% confidence interval (CI), 0.996-0.999; P<0.001], multiple births (OR, 1.885; 95%CI, 1.013-3.506; P=0.045), and non-invasive ventilation (OR, 0.288; 95%CI, 0.146-0.570; P<0.001) were identified as predictive factors for the prediction of severe ROP, by univariate analysis and multivariate analysis. For predicting severe ROP based on the internal validation group, the areas under receiver operating characteristic curve (AUC) was 78.1 (95%CI, 64.2-92.0) for the nomogram, 32.9 (95%CI, 15.3-50.5) for WINROP model, 70.2 (95%CI, 55.8-84.6) for Digirop-Birth model. In external validation group, AUC of the nomogram was also higher than that of WINROP model and Digirop-Birth model (80.2 versus 51.1 and 63.4). The decision curve analysis of the nomogram demonstrated better clinical efficacy than that of WINROP model and Digirop-Birth model. The calibration curves demonstrated a good consistency between the actual severe ROP incidence and the predicted probability. CONCLUSION: Birth weight, multiple births, and non-invasive ventilation are independent predictors of severe ROP. The nomogram has a good ability to predict severe ROP and performed well on internal validation and external validation in southeast China.

19.
J Ethnopharmacol ; 325: 117859, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38316218

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Endometriosis (EMs) is characterized by inflammatory lesions, dysmenorrhea, infertility, and chronic pelvic pain. Single-target medications often fail to provide systemic therapeutic results owing to the complex mechanism underlying endometriosis. Although traditional Chinese medicines-such as Juan-Tong-Yin (JTY)-have shown promising results, their mechanisms of action remain largely unknown. AIM OF THE STUDY: To elucidate the therapeutic mechanism of JTY in EMs, focusing on endoplasmic reticulum (ER) stress-induced autophagy. MATERIALS AND METHODS: The major components of JTY were detected using high-performance liquid chromatography-mass spectrometry (HPLC-MS). The potential mechanism of JTY in EMs treatment was predicted using network pharmacological analysis. Finally, the pathogenesis of EMs was validated in a clinical case-control study and the molecular mechanism of JTY was validated in vitro using endometrial stromal cells (ESCs). RESULTS: In total, 241 compounds were analyzed and identified from JTY using UPLC-MS. Network pharmacology revealed 288 targets between the JTY components and EMs. Results of the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses indicated that regulating autophagy, migration, apoptosis, and inflammation were the key mechanisms of JTY in treating EMs. Meanwhile, we found that protein kinase R-like endoplasmic reticulum kinase (PERK), Beclin-1, and microtubule-associated protein light chain 3 B (LC3B) expressions were lower in endometria of patients with EMs than in those with normal eutopic endometria (p < 0.05). Additionally, during in vitro experiments, treatment with 20% JTY-containing serum significantly suppressed ESC proliferation, achieving optimal effects after 48 h. Electron microscopy revealed significantly increased autophagy flux in the JTY group compared with the control group. Moreover, JTY treatment significantly reduced the migratory and invasive abilities of ESCs and upregulated protein expression of PERK, eukaryotic initiation factor 2α (eIF2α)/phospho-eukaryotic initiation factor 2α (p-eIF2α), activating Transcription Factor-4 (ATF4), Beclin-1, and LC3BII/I, while subsequently downregulating NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and interleukin 18 (IL-18) expression. However, administration of GSK2656157-a highly selective PERK inhibitor-reversed these changes. CONCLUSION: JTY ameliorates EMs by activating PERK associated with unfolded protein reaction, enhancing cell ER stress and autophagy, improving the inflammatory microenvironment, and decreasing the migration and invasion of ESCs.


Subject(s)
Endometriosis , Signal Transduction , Female , Humans , Beclin-1/metabolism , Endometriosis/pathology , Case-Control Studies , Chromatography, Liquid , Tandem Mass Spectrometry , Endoplasmic Reticulum Stress , Autophagy , Apoptosis , Stromal Cells/metabolism , Stromal Cells/pathology , Peptide Initiation Factors/metabolism , Peptide Initiation Factors/pharmacology
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