Brain alteration of autoimmune thyroid disease: Neuropsychiatric impact, neuroimaging insights, and neurobiological implications.

Autoimmune thyroid disease (AITD) is the most common organ-specific autoimmune disease, characterized by thyroid function disorder and autoimmune imbalance. Previous studies have demonstrated the decreased quality of life and neuropsychiatric manifestations in AITD patients, including anxiety, depression, cognitive impairment and affective disorder. These problems also plague the euthyroid AITD patients. Advanced neuroimaging techniques were well carried out and employed as an explanatory instrument for the above intriguing phenomenon. In recent years, an increasing number of neuroimaging studies have reported that these neuropsychiatric manifestations are accompanied by significant structural and functional brain alterations in AITD patients, mainly involved in neurocognitive and emotional regions, despite the underlying neurobiological mechanism is still unclear. The existing studies suggest that the potential pathogenesis of the neuropsychiatric manifestations and brain alterations does not depend on a single factor, but may result from a combination of thyroid function dysfunction, metabolic disorders, dysregulated autoimmune and trans-synaptic degeneration.

Bazi Bushen attenuates osteoporosis in SAMP6 mice by regulating PI3K-AKT and apoptosis pathways.

Osteoporosis (OP), a systemic skeletal disease, is characterized by low bone mass, bone tissue degradation and bone microarchitecture disturbance. Bazi Bushen, a Chinese patented medicine, has been demonstrated to be effective in attenuating OP, but the pharmacological mechanism remains predominantly unclear. In this study, the senescence-accelerated mouse prone 6 (SAMP6) model was used to explore bone homeostasis and treated intragastrically for 9 weeks with Bazi Bushen. In vivo experiments showed that Bazi Bushen treatment not only upregulated the levels of bone mineral density and bone mineral content but also increased the content of RUNX2 and OSX. Furthermore, the primary culture of bone mesenchymal stem cells (BMSCs) in SAMP6 mice was used to verify the effects of Bazi Bushen on the balance of differentiation between osteoblasts and adipocytes, as well as ROS and aging levels. Finally, the pharmacological mechanism of Bazi Bushen in attenuating OP was investigated through network pharmacology and experimental verification, and we found that Bazi Bushen could significantly orchestrate bone homeostasis and attenuate the progression of OP by stimulating PI3K-Akt and inhibiting apoptosis. In summary, our work sheds light on the first evidence that Bazi Bushen attenuates OP by regulating PI3K-AKT and apoptosis pathways to orchestrate bone homeostasis.

The insular cortex is not insular in thyroid eye disease: neuroimaging revelations of central-peripheral system interaction.

BACKGROUND: Thyroid eye disease (TED) is highly correlated with dysregulated immunoendocrine status. The insular cortex was found to regulate peripheral inflammation and immunomodulation in mice. This study aimed to explore whether the insular cortex in patients with TED played a modulatory role including the aberrant brain functional alteration and its association with immunoendocrine status. METHODS: This study included 34 active patients (AP), 30 inactive patients (IP) with TED, and 45 healthy controls (HC) matched for age, sex, and educational level. Comprehensive clinical details (especially immunoendocrine markers) and resting-state functional magnetic resonance imaging data were collected from each participant. The amplitude of low-frequency fluctuation (ALFF) was used to probe the aberrant alterations of local neural activity. The seed-based functional connectivity (FC) analysis was used to explore the relationship between the insular cortex and each voxel throughout the whole brain. The correlation analysis was conducted to assess the association between insular neurobiomarkers and immunoendocrine parameters. RESULTS: When compared with the IP and HC groups, the AP group displayed significantly higher ALFF values in the right insular cortex (INS.R) and lower FC values between the INS.R and the bilateral cerebellum. None of the neurobiomarkers differed between the IP and HC groups. Besides, correlations between insular neurobiomarkers and immunoendocrine markers (free thyroxine, the proportion of T cells, and natural killer cells) were identified in both AP and IP groups. CONCLUSIONS: This study was novel in reporting that the dysregulation of the insular cortex activity in TED was associated with abnormal peripheral immunoendocrine status. The insular cortex might play a key role in central-peripheral system interaction in TED. Further research is crucial to enhance our understanding of the central-peripheral system interaction mechanisms involved in autoimmune diseases.

Whole-orbit radiomics: machine learning-based multi- and fused- region radiomics signatures for intravenous glucocorticoid response prediction in thyroid eye disease.

BACKGROUND: Radiomics analysis of orbital magnetic resonance imaging (MRI) shows preliminary potential for intravenous glucocorticoid (IVGC) response prediction of thyroid eye disease (TED). The current region of interest segmentation contains only a single organ as extraocular muscles (EOMs). It would be of great value to consider all orbital soft tissues and construct a better prediction model. METHODS: In this retrospective study, we enrolled 127 patients with TED that received 4·5 g IVGC therapy and had complete follow-up examinations. Pre-treatment orbital T2-weighted imaging (T2WI) was acquired for all subjects. Using multi-organ segmentation (MOS) strategy, we contoured the EOMs, lacrimal gland (LG), orbital fat (OF), and optic nerve (ON), respectively. By fused-organ segmentation (FOS), we contoured the aforementioned structures as a cohesive unit. Whole-orbit radiomics (WOR) models consisting of a multi-regional radiomics (MRR) model and a fused-regional radiomics (FRR) model were further constructed using six machine learning (ML) algorithms. RESULTS: The support vector machine (SVM) classifier had the best performance on the MRR model (AUC = 0·961). The MRR model outperformed the single-regional radiomics (SRR) models (highest AUC = 0·766, XGBoost on EOMs, or LR on OF) and conventional semiquantitative imaging model (highest AUC = 0·760, NaiveBayes). The application of different ML algorithms for the comparison between the MRR model and the FRR model (highest AUC = 0·916, LR) led to different conclusions. CONCLUSIONS: The WOR models achieved a satisfactory result in IVGC response prediction of TED. It would be beneficial to include more orbital structures and implement ML algorithms while constructing radiomics models. The selection of separate or overall segmentation of orbital soft tissues has not yet attained its final optimal result.

White Matter Alterations of Visual Pathway in Thyroid Eye Disease: A Fixel-Based Analysis.

BACKGROUND: Thyroid eye disease (TED), particularly its sight-threatening complication, dysthyroid optic neuropathy (DON), profoundly impacts patients' visual health. The pathological changes in the white matter (WM) fibers within the intracranial visual pathway in TED have been infrequently studied. Understanding these changes holds crucial importance for exploring the pathogenesis and prognosis of TED. PURPOSE: To utilize fixel-based analysis (FBA) to clarify the type of microstructural damage occurring in the visual pathway in TED. STUDY TYPE: Prospective. SUBJECTS: 28 TED with DON patients (11 males and 17 females), 28 TED without DON (non-DON) patients (12 males and 16 females), and 28 healthy controls (HCs) (12 males and 16 females). FIELD STRENGTH/SEQUENCE: 3 T; multishell diffusion MRI using echo planar imaging. ASSESSMENT: Fiber density (FD) and fiber-bundle cross-section (FC) were calculated to characterize WM microstructural alteration in TED visual pathway. The correlations between FBA metrics and visual field index and mean deviation were examined. STATISTICAL TESTS: One-way analysis of variance, Kruskal-Wallis, t-tests, Mann-Whitney U, Chi-square, and Pearson correlation, were conducted with false discovery rate and family wise error corrections. Significance was set at P < 0.05. RESULTS: Both DON and non-DON groups showed significant FD loss in the right optic tract compared with HCs, with DON patients experiencing more severe FD loss. Only DON patients had FD loss in the right optic radiation (OR) compared with the non-DON patients and HCs, with no FC difference across groups. FD in DON patients' ORs significantly correlated with visual field index (r = 0.857) and mean deviation (r = 0.751). DATA CONCLUSION: Both DON and non-DON affect the WM microstructure of the visual pathway to varying extents. Visual field metrics can reflect the severity of FD damage to the OR in the visual pathway of DON patients. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 3.

Radiomics in ophthalmology: a systematic review.

BACKGROUND: Radiomics holds great potential in medical image analysis for various ophthalmic diseases. In recent times, there have been numerous endeavors in this area of research. This systematic review aims to provide a comprehensive assessment of the strengths and limitations of radiomics in ophthalmology. METHOD: Conforming to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, we conducted a systematic review with a pre-registered protocol (PROSPERO: CRD42023446317). We explored the PubMed, Embase, and Cochrane databases for original studies on this topic and made a comprehensive descriptive integration. Furthermore, the included studies underwent quality assessment by the radiomics quality score (RQS). RESULTS: A total of 41 articles from an initial search of 227 studies were finally selected for further analysis. These articles included research across five disease categories and covered seven imaging modalities. The radiomics models demonstrated robust performance, with area under the curve (AUC) values mostly falling within 0.7-1.0. The moderate RQS (mean score: 11.17/36) indicated that most studies were retrospectively, single-center analyses without external validation. CONCLUSIONS: Radiomics holds promising utility in the field of ophthalmology, assisting diagnosis, early-stage screening, and prognostication of treatment response. Artificial intelligence algorithms significantly contribute to the construction of radiomics models in ophthalmology. This study highlights the strengths and challenges of radiomics in ophthalmology and suggests potential avenues for future improvement. CLINICAL RELEVANCE STATEMENT: Radiomics represents a valuable approach for generating innovative imaging markers, enhancing efficiency in clinical diagnosis and treatment, and aiding decision-making in clinical contexts of many ophthalmic diseases, thereby improving overall patient prognosis. KEY POINTS: Radiomics has attracted extensive attention in the field of ophthalmology. Articles included five disease categories over seven imaging modalities, consistently yielding AUCs mostly above 0.7. Current research has few prospective and multi-center studies, underlining the necessity for future high-quality studies.

Immune-related visual dysfunction in thyroid eye disease: a combined orbital and brain neuroimaging study.

OBJECTIVES: To investigate the pathological interplay between immunity and the visual processing system (VPS) in thyroid eye disease (TED). METHODS: A total of 24 active patients (AP), 26 inactive patients (IP) of TED, and 27 healthy controls (HCs) were enrolled. Orbital magnetic resonance imaging (MRI) and resting-state functional MRI (rs-fMRI) were conducted for each participant. Multiple MRI parameters of the intraorbital optic nerve (ON) were assessed. The amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) were calculated. Correlation analyses were carried out on the above parameters and clinical characteristics. RESULTS: Visual functioning scores differentiated between the AP and IP groups. The ON subarachnoid space and ON sheath diameter were significantly higher in AP than in IP. Six vision-related brain regions were identified in TED patients compared with HCs, including right calcarine (CAL.R), right cuneus (CUN.R), left postcentral gyrus (PoCG.L), right middle temporal gyrus (MTG.R), left superior frontal gyrus (SFG.L), and left caudate (CAU.L). The brain activity of MTG.R, SFG.L, and CAU.L differentiated between the AP and IP groups. The correlation analysis revealed a close association among the vision-related brain regions, MRI parameters of ON, and clinical characteristics in AP and IP, respectively. CONCLUSIONS: Combined orbital and brain neuroimaging revealed abnormalities of the VPS in TED, which had a close correlation with immune statuses. Vision-related brain regions in TED might be possibly altered by peripheral immunity via a direct or indirect approach. CLINICAL RELEVANCE STATEMENT: The discovery of this study explained the disparity of visual dysfunction in TED patients with different immune statuses. With the uncovered neuroimaging markers, early detection and intervention of visual dysfunction could be achieved and potentially benefit TED patients. KEY POINTS: • Patients with different immune statuses of thyroid eye disease varied in the presentation of visual dysfunction. • The combined orbital and brain neuroimaging study identified six altered vision-related brain regions, which had a significant correlation with the MRI parameters of the intraorbital optic nerve and immunological characteristics. • Peripheral immunity might possibly give rise to alterations in the central nervous system part of the visual processing system via a direct or indirect approach.

Efficacy of platelet-rich plasma in the treatment of thin endometrium: a meta-analysis of randomized controlled trials.

BACKGROUND: Thin endometrium (TE) is a common cause of female infertility in clinical practice. Platelet-rich Plasma (PRP) therapy becomes a novel treatment for thin endometrium; however, its clinical application remains controversial. This meta-analysis aims to evaluate the therapeutic effects of intrauterine autologous PRP infusion in women with thin endometrium through relevant randomized controlled trials (RCTs). METHODS: We systematically searched studies published in English from inception until June 2024 in databases such as PubMed, The Cochrane Library, Embase, Web of Science, and MEDLINE. Search terms included "Platelet-Rich Plasma," "thin endometrium," "endometrial thickness," "infertility," "pregnancy," "reproduction," and "adverse reactions". RCTs identified through the search were subjected to systematic review and meta-analysis, and data were analyzed using fixed-effects or random-effects models based on heterogeneity. RESULTS: Eight RCTs involving 678 patients with thin endometrium were included. Patients receiving PRP infusion demonstrated significantly superior outcomes compared to the control group in endometrial thickness (MD: 1.23, 95%CI: 0.87 to 1.59, P = 0.000), clinical pregnancy rate (RR: 2.04, 95%CI: 1.52 to 2.76, P = 0.000), live birth rate (RR: 2.46; 95%CI: 1.57 to 3.85, P = 0.000), cycle cancellation rate (RR: 0.46, 95%CI: 0.23 to 0.93, P = 0.000), and embryo implantation rate (RR: 2.71; 95%CI: 1.91 to 3.84, P = 0.000). There were no statistically significance in spontaneous abortion rate (RR: 0.85, 95%CI: 0.40 to 1.78, P = 0.659), chemical pregnancy rate (RR: 1.84, 95%CI: 0.72 to 4.72, P = 0.204) and endometrial vascular improvement rate (RR: 1.10; 95%CI: 0.89 to 1.38, P = 0.367) between the two groups. The limitations of this study includes that, we only included single lauguage for literature research, the sample size and heterogeneity which could cause criteria bias. CONCLUSION: Intrauterine PRP infusion may be an effective and safe treatment for women with thin endometrium. Further high-quality, large-sample, randomized controlled trials are needed to validate the reliability of our results. TRIAL REGISTRATION: The review protocol is registered on PROSPERO with registration number CRD42023490421, and no modifications were made to the information provided at registration.

Peripheral CD3+CD4+ T cells as indicators of disease activity in thyroid eye disease: age-dependent significance.

PURPOSE: To provide an in-depth analysis of the association of peripheral lymphocytes and the disease activity of thyroid eye disease (TED). METHODS: This retrospective study enrolled 65 active TED patients and 46 inactive TED patients. Comparative analyses of peripheral lymphocyte subsets were conducted between active and inactive patients. Subgroup analyses were performed based on sex, age, disease duration, and severity. Correlation analyses explored the associations between lymphocyte subsets and TED activity indicators. Prediction models for TED activity were established using objective indicators. RESULTS: Significantly elevated levels of CD3+CD4+ T cells were observed in active TED patients compared to inactive patients (P = 0.010). Subgroup analyses further revealed that this disparity was most prominent in females (P = 0.036), patients aged 50 years and younger (P = 0.003), those with long-term disease duration (P = 0.022), and individuals with moderate-to-severe disease (P = 0.021), with age exerting the most substantial impact. Subsequent correlation analysis confirmed the positive association between CD3+CD4+ T cells and the magnetic resonance imaging indicator of TED activity among patients aged 50 years and younger (P = 0.038). The combined prediction models for TED activity, established using objective indicators including CD3+CD4+ T cells, yielded areas under curve of 0.786 for all patients and 0.816 for patients aged 50 years and younger. CONCLUSIONS: Peripheral CD3+CD4+ T cells are associated with disease activity of TED, especially in patients aged 50 years and younger. Our study has deepened the understanding of the peripheral T cell profiles in TED patients.

Spiritual care needs and their attributes among Chinese inpatients with advanced breast cancer based on the Kano model: a descriptive cross-sectional study.

BACKGROUND: Numerous previous research have established the need for spiritual care among patients with cancer globally. Nevertheless, there was limited research, primarily qualitative, on the spiritual care needs of Chinese inpatients with advanced breast cancer. Furthermore, the need for spiritual care was rarely explored using the Kano model. To better understand the spiritual care needs and attributes characteristics of inpatients with advanced breast cancer, this study examined the Kano model. METHODS: A descriptive cross-sectional design study was conducted in the oncology departments of three tertiary grade-A hospitals in China from October 2022 to May 2023. To guarantee high-quality reporting of the study, the Strengthening the Reporting of Observational Studies in Epidemiology Checklist was used. Data on the demographic characteristics questionnaire, the Nurse Spiritual Therapeutics Scale (NSTS), and the Kano model-based Nurse Spiritual Therapeutics Attributes Scale (K-NSTAs) were collected through convenience sampling. The Kano model, descriptive statistics, two independent samples t-tests, and one-way analysis of variance were used to analyze the data. RESULTS: The overall score for spiritual care needs was 31.16 ± 7.85. The two dimensions with the highest average scores, "create a good atmosphere" (3.16 ± 0.95), and the lowest average scores, "help religious practice" (1.72 ± 0.73). The 12 items were distributed as follows: three attractive attributes were located in Reserving Area IV; five one-dimensional attributes were distributed as follows: three one-dimensional attributes were located in Predominance Area I, and two were found in Improving Area II; two must-be attributes were located in Improving Area II; and two indifference attributes were located in Secondary Improving Area III. CONCLUSION: The Chinese inpatients with advanced breast cancer had a middle level of spiritual care needs, which need to be further improved. Spiritual care needs attributes were defined, sorted, categorized, and optimized accurately and perfectly by the Kano model. And "create a good atmosphere" and "share self-perception" were primarily one-dimensional and must-be attributes. In contrast, the items in the dimensions of "share self-perception" and "help thinking" were principally attractive attributes. Nursing administrators are advised to optimize attractive attributes and transform indifference attributes by consolidating must-be and one-dimensional attributes, which will enable them to take targeted spiritual care measures based on each patient's characteristics and unique personality traits.

Evaluating the Significance of Fasting C-peptide in Conjunction with the Insulin Resistance Index for Assessing Hepatic Fibrosis in Patients with Type 2 Diabetes Mellitus and Nonalcoholic Fatty Liver Disease.

Background: Non-alcoholic fatty liver disease (NAFLD) has reached pandemic proportions globally, particularly affecting individuals with type 2 diabetes mellitus (T2DM). Objective: Our study aims to elucidate the diagnostic value of fasting C-peptide in combination with insulin resistance for assessing hepatic fibrosis in patients with T2DM and comorbid NAFLD. Design: This was a retrospective study. Setting: The study was conducted at the Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine. Participants: The research involved 76 type 2 diabetes mellitus patients with nonalcoholic fatty liver disease, diagnosed at our hospital from April 2020 to October 2022. Patients were categorized into the non-progressive hepatic fibrosis group (n = 64) and progressive hepatic fibrosis group (n = 12) based on fibrosis-4 value. Interventions: General data, systolic/diastolic blood pressure, fasting plasma glucose, fasting C-peptide, fasting insulin, glycosylated hemoglobin, uric acid, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, aspartate transaminase, alanine transaminase, and γ-glutamyl transferase were collected. Insulin resistance was calculated using a designated formula. Primary Outcomes Measures: The predictive impact of fasting C-peptide in combination with insulin resistance was evaluated through receiver operating characteristic curves. Results: The age, body mass index, fasting C-peptide, fasting insulin, aspartate transaminase, and insulin resistance showed a significant increase in the progressive hepatic fibrosis group compared to the non-progressive group (P = .006, P = .014, P < .001, P < .001, P = .004, and P = .021). The combination's sensitivity demonstrated an elevation compared to fasting C-peptide or insulin resistance alone (P = .005). Conclusions: Fasting C-peptide in combination with insulin resistance proves to have a substantial predictive impact on hepatic fibrosis in type 2 diabetes mellitus patients with nonalcoholic fatty liver disease, holding valuable clinical diagnostic potential.

Whole-orbit-based multiparametric assessment of disease activity of thyroid eye disease on Dixon MRI.

PURPOSE: This study aimed to explore the diagnostic value of whole-orbit-based multiparametric assessment on Dixon MRI for the evaluation of the thyroid eye disease (TED) activity. METHODS: The retrospective study enrolled patients diagnosed as TED and obtained their axial and coronal Dixon MRI scans. Multiparameters were assessed, including water fraction (WF), fat fraction (FF) of extraocular muscles (EOMs), orbital fat (OF), and lacrimal gland (LG). The thickness of OF and herniation of LG were also measured. Univariable and multivariable logistic regression was applied to construct prediction models based on single or multiple structures. Receiver operating characteristic (ROC) curve analysis was also implemented. RESULTS: Univariable logistic analysis revealed significant differences in water fraction (WF) of the superior rectus (P = 0.018), fat fraction (FF) of the medial rectus (P = 0.029), WF of OF (P = 0.004), and herniation of LG (P = 0.012) between the active and inactive TED phases. Multivariable logistic analysis and corresponding receiver operating characteristic curve (ROC) analysis of each structure attained the area under the curve (AUC) values of 0.774, 0.771, and 0.729 for EOMs, OF, and LG, respectively, while the combination of the four imaging parameters generated a final AUC of 0.909. CONCLUSIONS: Dixon MRI may be used for fine multiparametric assessment of multiple orbital structures. The whole-orbit-based model improves the diagnostic performance of TED activity evaluation.

Bazi Bushen alleviates skin senescence by orchestrating skin homeostasis in SAMP6 mice.

Bazi Bushen, a Chinese-patented drug with the function of relieving fatigue and delaying ageing, has been proven effective for extenuating skin senescence. To investigate the potential mechanism, senescence-accelerated mouse prone 6 (SAMP6) was intragastrically administered with Bazi Bushen for 9 weeks to induce skin homeostasis. Skin homeostasis is important in mitigating skin senescence, and it is related to many factors such as oxidative stress, SASP, apoptosis, autophagy and stem cell. In our study, skin damage in SAMP6 mice was observed using HE, Masson and SA-ß-gal staining. The content of hydroxyproline and the activities of SOD, MDA, GSH-PX and T-AOC in the skin were measured using commercial assay kits. The level of SASP factors (IL-6, IL-1ß, TNF-α, MMP2 and MMP9) in skin were measured using ELISA kits. The protein expressions of p16, p21, p53, Bax, Bcl-2, Cleaved caspase-3, LC3, p62, Beclin1, OCT4, SOX2 and NANOG were measured by western blotting. The expression of ITGA6 and COL17A1 was measured by immunofluorescence staining and western blotting. Our findings demonstrated that Bazi Bushen alleviated skin senescence by orchestrating skin homeostasis, reducing the level of oxidative stress and the expression of SASP, regulating the balance of apoptosis and autophagy and enhancing the protein expressions of ITGA6 and COL17A1 to improve skin structure in SAMP6 mice. This study indicated that Bazi Bushen could serve as a potential therapy for alleviating skin senescence.

Development and application of animal models to study thyroid-associated ophthalmopathy.

Thyroid-associated ophthalmopathy (TAO), also known as Graves' ophthalmopathy, is an autoimmune disease that is usually accompanied by hyperthyroidism. Its pathogenesis involves the activation of autoimmune T lymphocytes by a cross-antigen reaction of thyroid and orbital tissues. The thyroid-stimulating hormone receptor (TSHR) is known to play an important role in the development of TAO. Because of the difficulty of orbital tissue biopsy, the establishment of an ideal animal model is important for developing novel clinical therapies of TAO. To date, TAO animal modeling methods are mainly based on inducing experimental animals to produce anti-thyroid-stimulating hormone receptor antibodies (TRAbs) and then recruit autoimmune T lymphocytes. Currently, the most common methods are hTSHR-A subunit plasmid electroporation and hTSHR-A subunit adenovirus transfection. These animal models provide a powerful tool for exploring the internal relationship between local and systemic immune microenvironment disorders of the TAO orbit, facilitating the development of new drugs. However, existing TAO modeling methods still have some defects, such as low modeling rate, long modeling cycles, low repetition rate, and considerable differences from human histology. Hence, the modeling methods require further innovation, improvement, and in-depth exploration.

Application of Quantitative MRI in Thyroid Eye Disease: Imaging Techniques and Clinical Practices.

Thyroid eye disease (TED) is a complex autoimmune disorder that impairs various orbital structures, leading to cosmetic damage and vision loss. Magnetic resonance imaging (MRI) is a fundamental diagnostic tool utilized in clinical settings of TED, for its accurate demonstration of orbital lesions and indication of disease conditions. The application of quantitative MRI has brought a new prospect to the management and research of TED, offering more detailed information on morphological and functional changes in the orbit. Therefore, many researchers concentrated on the implementation of different quantitative MRI techniques on TED for the exploration of clinical practices. Despite the abundance of studies utilizing quantitative MRI in TED, there remain considerable barriers and disputes on the best exploitation of this tool. This could possibly be attributed to the complexity of TED and the fast development of MRI techniques. It is necessary that clinical and radiological aspects of quantitative MRI in TED be better integrated into comprehensive insights. Hence, this review traces back 30 years of publications regarding quantitative MRI utilized in TED and elucidates this promising application in the facets of imaging techniques and clinical practices. We believe that a deeper understanding of the application of quantitative MRI in TED will enhance the efficacy of the multidisciplinary management of TED. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

Engineering of Stable Anionic/Neutral MOFs with Zinc-Adeninate Building Units for Efficient C2H2/CO2 Separation.

Using adenine and metal ions to form secondary building units (SBUs), further connected by a highly symmetrical multicarboxylic linker to construct an amino-modified porous framework with high porosity, is an effective strategy. By regulating the deprotonation and hydrolysis capacity of the synthesized solvent, it is possible to obtain different charged frameworks. In this work, two stable anionic/neutral MOFs, (Et2NH2)[Zn3(TCPE)(adenine)2CH3COO]·DEF·3H2O (1) and [Zn3.5(adenine)(TCPE)1.5(DMA)(H2O)0.5]·2DMA·2H2O (2), have been synthesized based on zinc-adeninate building units and symmetric tetrakis(4-carboxyphenyl)ethylene (H4TCPE) in N,N-diethylformamide (DEF) and N,N-dimethylacetamide (DMA) reaction systems, respectively. 1 is an anionic framework based on 1D rod zinc-adeninate SBU, containing 1D rectangular (14.3 × 6.3 Å2) and square (14.3 × 14.3 Å2) channels. While 2 is a neutral framework built from isolated zinc-adeninate SBU, it contains hexagonal cages with a dimension of 5.5 Å in the structure. Both of them have high porosity (61.6% for 1 and 46.3% for 2) and high stability in a wide range of pH. 1 and 2 show high C2H2 adsorption capacity at 298 K (48.1 and 70.1 cm3 g-1, respectively) and selective capacity for C2H2/CO2 mixtures, which was confirmed by the breakthrough experiments. Furthermore, the interaction between the frameworks and gas molecules has also been explained by theoretical calculation. This work provides a good example of the design and regulation of porous structures for adsorption and separation functions.

An investigation of the mechanism of ZiyinDianji decoction in treating follicular dysplasia based on network pharmacology and molecular docking.

Follicular development disorder is a common gynaecological endocrine disease that can cause infertility, menstrual disorders, abortion, and other complications. ZiyinDianji decoction (ZYDJD) is a commonly used traditional Chinese medicine in clinical practice to promote follicular growth and development, but its pharmacological activity and mechanism of action are not clear. We combined network pharmacology with molecular docking and in vivo animal experiments to investigate the mechanism of ZYDJD in follicular development disorder. Cytoscape software was used for constructing ZYDJD-active component-target and PPI networks. GO biological process and KEGG pathway enrichment analyses were performed. The main components and key targets were selected for molecular docking. Finally, animal experiments were conducted for validation. The network pharmacology results showed that ZYDJD contained 83 active components and 159 core targets. The six most important active components were quercetin, luteolin, kaempferol, baicalein, isorhamnetin, and ß-sitosterol, and the most important disease targets were AKT1, TNF, IL-6, and P53. GO analysis mainly involved 470 cell biological processes, including effect on hormones, vascular morphogenesis, development, and cell proliferation. KEGG analysis involved cancer pathways, lipid metabolism pathways, and PI3K/AKT signalling pathways. Molecular docking showed good results, and animal experiments further verified that ZYDJD prevented cyclophosphamide from causing excessive activation of primordial follicles. ZYDJD maintained ovarian reserve and reproductive function by inhibiting the hyperphosphorylation of key molecules of the PI3K/Akt pathway, reducing FOXO3a, thereby ensuring the development of normal follicles. In conclusion, based on network pharmacology, molecular docking, and animal experiments, ZYDJD may act through the PI3K/Akt/FOXO3a pathway.

Granule Dendrobii suppresses chronic atrophic gastritis induced by N-methyl-N'-nitro-N-nitrosoguanidine by modulating the gastrointestinal bacteria in rats.

Chronic atrophic gastritis (CAG) is an important stage in the transformation of the normal gastric mucosa into gastric cancer. Granule Dendrobii (GD), a proprietary Chinese medicine, has proven clinical efficacy in treating CAG. GD might promote the reversal of precancerous lesions by improving them in CAG patients. However, the mechanism of GD in CAG treatment is relatively less understood. Here, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced CAG rats were treated with GD and its efficacy was evaluated by observing the changes in the rats' weight and the pathology of gastric tissues. The potential effect of GD on the bacteria was predicted and verified in the large and small intestines and stomachs of CAG rats using amplicon sequencing and RT-qPCR. The results showed that GD could ameliorate the symptoms of body weight loss in CAG rats. Hematoxylin-Eosin (HE) and Alcian Blue (AB) staining showed that GD significantly improved the pathological state of the gastric mucosa in CAG rats. The relative abundance (RA) of Lactobacillus and Turicibacter significantly decreased after GD intervention compared with that of the model group (P < 0.05), indicating that GD might improve CAG by regulating the RA of Lactobacillus and Turicibacter. These findings revealed that Lactobacillus and Turicibacter as bacteria agents associated with gastritis, have the potential to inhibit gastric cancer, especially Turicibacter maybe another pathogen of CAG besides Helicobacter pylori (HP), which is worthy of further study. Meanwhile, the findings provided new ideas and materials for the research and development of new CAG drugs.

Hyperhubeins A-I, Bioactive Sesquiterpenes with Diverse Skeletons from Hypericum hubeiense.

Nine new sesquiterpenes, hyperhubeins A-I (1-9), and 14 known analogues (10-23) were isolated from the aerial portions of Hypericum hubeiense. Their structures and absolute configurations were determined unambiguously via spectroscopic analysis, single-crystal X-ray diffraction, and electronic circular dichroism calculations. Compounds 1-3 possess an unprecedented sesquiterpene carbon skeleton. Further, a plausible biosynthetic pathway from farnesyl diphosphate (FPP) is proposed. The isolated phytochemicals were evaluated for neuroprotective and anti-neuroinflammatory properties in vitro. Compounds 1, 2, 5-8, 14, and 21 displayed notable neuroprotective activity against hydrogen peroxide (H2O2)-induced lesions in PC-12 cells at 10 µM. Additionally, compounds 1, 2, 12, and 13 exhibited inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV-2 microglial cells, with their IC50 values ranging from 4.92 to 6.81 µM. Possible interactions between these bioactive compounds and inducible nitric oxide synthase (iNOS) were predicted via molecular docking. Moreover, Western blotting indicated that compound 12 exerted anti-neuroinflammatory activity by suppressing LPS-stimulated expression of toll-like receptor-4 (TLR-4) and inhibiting consequent activation of nuclear factor-kappa-B (NF-κB) signaling.

Retracted: The Flavanone, Naringenin, Modifies Antioxidant and Steroidogenic Enzyme Activity in a Rat Model of Letrozole-Induced Polycystic Ovary Syndrome.

The authors requested retraction after reviewing the manuscript and determining that there were errors in the data. Reference: Yanli Hong, Yanyun Yin, Yong Tan, Ke Hong, Huifang Zhou. The Flavanone, Naringenin, Modifies Antioxidant and Steroidogenic Enzyme Activity in a Rat Model of Letrozole-Induced Polycystic Ovary Syndrome. Med Sci Monit, 2019; 25: 395-401. DOI: 10.12659/MSM.912341.