Pathological Changes In Patients Research Articles

Screening of pathologically significant diagnostic biomarkers in tears of thyroid eye disease based on bioinformatic analysis and machine learning.

Lacrimal gland enlargement is a common pathological change in patients with thyroid eye disease (TED). Tear fluid has emerged as a new source of diagnostic biomarkers, but tear-based diagnostic biomarkers for TED with high efficacy are still lacking. We aim to investigate genes associated with TED-associated lacrimal gland lesions. Additionally, we seek to identify potential biomarkers for diagnosing TED in tear fluid. We obtained two expression profiling datasets related to TED lacrimal gland samples from the Gene Expression Omnibus (GEO). Subsequently, we combined the two separate datasets and conducted differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) on the obtained integrated dataset. The genes were employed for Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The genes were intersected with the secretory proteins profile to get the potential proteins in the tear fluid. Machine learning techniques were then employed to identify optimal biomarkers and develop a diagnostic nomogram for predicting TED. Finally, gene set enrichment analysis (GSEA) and immune infiltration analysis were conducted on screened hub genes to further elucidate their potential mechanisms in TED. In our analysis of the integrated TED dataset, we identified 2,918 key module genes and 157 differentially expressed genes and finally obtained 84 lacrimal-associated key genes. Enrichment analysis disclosed that these 84 genes primarily pertain to endoplasmic reticulum organization. After intersecting with the secretory proteins, 13 lacrimal gland-associated secretory protein genes (LaSGs) were identified. The results from machine learning indicated the substantial diagnostic value of dyslexia associated gene (KIAA0319) and peroxiredoxin4 (PRDX4) in TED-associated lacrimal gland lesions. The two hub genes were chosen as candidate biomarkers in tear fluid and employed to establish a diagnostic nomogram. Furthermore, single-gene GSEA results and immune cell infiltration analysis unveiled immune dysregulation in the lacrimal gland of TED, with KIAA0319 and PRDX4 showing significant associations with infiltrating immune cells. We uncovered the distinct pathophysiology of TED-associated lacrimal gland enlargement compared to TED-associated orbital adipose tissue enlargement. We have demonstrated the endoplasmic reticulum-related pathways involved in TED-associated lacrimal gland lesions and established a diagnostic nomogram for TED utilizing KIAA0319 and PRDX4 through integrated bioinformatics analysis. This contribution offers novel insights for non-invasive, prospective diagnostic approaches in the context of TED.

Risk-stratified management of cervical high-grade squamous intraepithelial lesion based on machine learning.

The concordance rate between conization and colposcopy-directed biopsy (CDB) proven cervical high-grade squamous intraepithelial lesion (HSIL) were 64-85%. We aimed to identify the risk factors associated with pathological upgrading or downgrading after conization in patients with cervical HSIL and to provide risk-stratified management based on a machine learning predictive model. This retrospective study included patients who visited the Obstetrics and Gynecology Hospital of Fudan University from January 1 to December 31, 2019, were diagnosed with cervical HSIL by CDB, and subsequently underwent conization. A wide variety of data were collected from the medical records, including demographic data, laboratory findings, colposcopy descriptions, and pathological results. The patients were categorized into three groups according to their postconization pathological results: low-grade squamous intraepithelial lesion (LSIL) or below (downgrading group), HSIL (HSIL group), and cervical cancer (upgrading group). Univariate and multivariate analyses were performed to identify the independent risk factors for pathological changes in patients with cervical HSIL. Machine learning prediction models were established, evaluated, and subsequently verified using external testing data. In total, 1585 patients were included, of whom 65 (4.1%) were upgraded to cervical cancer after conization, 1147 (72.4%) remained having HSIL, and 373 (23.5%) were downgraded to LSIL or below. Multivariate analysis showed a 2% decrease in the incidence of pathological downgrade for each additional year of age and a 1% increase in lesion size. Patients with cytology > LSIL (odds ratio [OR] = 0.33; 95% confidence interval [CI], 0.21-0.52), human papillomavirus (HPV) infection (OR = 0.33; 95% CI, 0.14-0.81), HPV 33 infection (OR = 0.37; 95% CI, 0.18-0.78), coarse punctate vessels on colposcopy examination (OR = 0.14; 95% CI, 0.06-0.32), HSIL lesions in the endocervical canal (OR = 0.48; 95% CI, 0.30-0.76), and HSIL impression (OR = 0.02; 95% CI, 0.01-0.03) were less likely to experience pathological downgrading after conization than their counterparts. The independent risk factors for pathological upgrading to cervical cancer after conization included the following: age (OR = 1.08; 95% CI, 1.04-1.12), HPV 16 infection (OR = 4.07; 95% CI, 1.70-9.78), the presence of coarse punctate vessels during colposcopy examination (OR = 2.21; 95% CI, 1.08-4.50), atypical vessels (OR = 6.87; 95% CI, 2.81-16.83), and HSIL lesions in the endocervical canal (OR = 2.91; 95% CI, 1.46-5.77). Among the six machine learning prediction models, the back propagation (BP) neural network model demonstrated the highest and most uniform predictive performance in the downgrading, HSIL, and upgrading groups, with areas under the curve (AUCs) of 0.90, 0.84, and 0.69; sensitivities of 0.74, 0.84, and 0.42; specificities of 0.90, 0.71, and 0.95; and accuracies of 0.74, 0.84, and 0.95, respectively. In the external testing set, the BP neural network model showed a higher predictive performance than the logistic regression model, with an overall AUC of 0.91. Therefore, a web-based prediction tool was developed in this study. BP neural network prediction model has excellent predictive performance and can be used for the risk stratification of patients with CDB-diagnosed HSIL.

ZiBu PiYin recipe regulates central and peripheral Aβ metabolism and improves diabetes-associated cognitive decline in ZDF rats

Ethnopharmacological relevanceCognitive impairment caused by central neuropathy in type 2 diabetes mellitus (T2DM), namely diabetes-associated cognitive decline (DACD), is one of the common complications in patients with T2DM. Studies have shown that brain β-amyloid (Aβ) deposition is a typical pathological change in patients with DACD, and that there is a close relationship between intestinal microorganisms and cognitive impairment. However, the specific mechanism(s) of alteration in Aβ metabolism in DACD, and of the correlation between Aβ metabolism and intestinal microorganisms remain unknown. Aim of the studyRevealing the mechanism of ZBPYR regulating Aβ metabolism and providing theoretical basis for clinical evaluation and diagnosis of DACD. Materials and methodsWe characterized Aβ metabolism in the central and peripheral tissues of Zucker diabetic fatty (ZDF) rats with DACD, and then explored the preventive and therapeutic effects of ZiBu PiYin Recipe (ZBPYR). Specifically, we assessed these animals for the formation, transport, and clearance of Aβ; the morphological structure of the blood-brain barrier (BBB); and the potential correlation between Aβ metabolism and intestinal microorganisms. ResultsZBPYR provided improvements in the structure of the BBB, attenuation of Aβ deposition in the central and peripheral tissues, and a delay in the development of DACD by improving the expression of Aβ production, transport, and clearance related protein in ZDF rats. In addition, ZBPYR improved the diversity and composition of intestinal microorganisms, decreased the abundance of Coprococcus, a bacterium closely related to Aβ production, and up regulate the abundance of Streptococcus, a bacterium closely related to Aβ clearance. ConclusionThe mechanism of ZBPYR ability to ameliorate DACD may be closely related to changes in the intestinal microbiome.

A retrospective study of the relationship between the presence of complaints and the identified pathological changes in the temporomandibular joint

Introduction. In the practice of an orthodontist, diseases of the temporomandibular joint (TMJ) are an urgent problem due to their widespread, diverse clinical manifestations.Goal. To study the relationship between the identified anatomical and functional disorders of the TMJ, as risk factors for complications during orthodontic treatment, and the presence of characteristic complaints in the structure of pathological changes in the TMJ.Materials and methods. According to the type of organization and the ratio of data collection time, the scientific study belonged to a longitudinal retrospective study, according to the type of observation: case-control. A retrospective analysis of 102 outpatient medical records of patients who sought medical help from an orthodontist at a dental clinic was carried out. The criterion for inclusion in the study was the presence of a newly diagnosed disease of the temporomandibular joint, mandatory radiological diagnostic methods. Magnetic resonance imaging (MRI) of the TMJ in the patient who sought medical help was used as a radiation diagnosis. As part of the scientific study, the structure of pathological changes in the TMJ was analyzed, the relationship between the presence of complaints and the revealed pathology was studied.Results. The analysis of the data showed that the MR examination of the TMJ reveals pathological changes in patients who sought orthodontic care, both with complaints and with an asymptomatic course of diseases. Data analysis did not show a statistically significant relationship between the presence of complaints and the revealed pathology in the case of degenerative (χ2 = 0.123; p > 0.05), inflammatory changes in the TMJ (χ2 = 0.123; p > 0.05) and pathological disorders of the masticatory muscles (F = 0.704; p > 0.05). The relationship is statistically significant, but weak for ventral dislocation without reposition (p < 0.05; φ = 0.107) and the dorsal arrangement of the disc (p < 0.05; φ = 0.101). In the case of ventral dislocation of the articular disc with the reposition, the relationship is statistically significant, of medium strength (p < 0.05; φ = 0.284).Conclusions. The results of a retrospective analysis of medical documentation confirm the need for instrumental research methods for all patients, regardless of whether they have any complaints at the stage of determining the optimal tactics of orthodontic intervention to obtain diagnostic information on the state of the TMJ in order to prevent the risks of complications during orthodontic treatment.

Clinical and diagnostic features of repeated mild traumatic brain injuries

Repeated mild traumatic brain injury (TBI) leads to new changes and exacerbates the existing ones caused by the primary trauma. The pathogenetic mechanisms of repeated TBI are the result of traumatic effects and their cumulation. They cause various morphological and functional changes in the brain. Objective — to improve the diagnosis of pathological changes in patients with repeated mild traumatic brain injury. Materials and methods. The study involved 199 patients with a history of repeated mild TBI. Men predominated among them — 158 (79.40 %). There were 80 (40.20 %) patients of youthful age (17—24 years), 78 (39.20 %) of young age (25—44 years), and 41 (20.60 %) of middle-aged (45—60 years). The number of repeated TBIs per patient ranged from two to five. All patients were examined in the remote period of TBI. The control group consisted of 30 people aged 18 to 50 years (mean age — (33.11 ± 3.09) years) who had no history of TBI. Cognitive impairment (CI) was assessed by neuropsychological examination using the Mini-Mental State Examination (MMSE), the Frontal Area Battery (FAB), and the clock drawing test. Methods of neuropsychological analysis, neuroimaging and neurophysiological methods were used. The data of clinical and neurological examinations and studies of cognitive functions were analyzed, structural changes of the brain and cerebrospinal tract were established on the basis of neuroimaging studies of the brain, and the peculiarities of cerebral hemodynamics in patients with mild repeated TBI were determined. The characteristics of neurophysiological changes in patients are given based on the study of the features of electroencephalographic changes and the study of cognitive evoked potentials of the brain. The immune status was evaluated in patients who had repeated mild TBI. Results. Repeated TBI in our study was observed in the form of mild concussions and brain contusions. Their number in one patient ranged from 1 to 5. Clinical manifestations of repeated mild TBI had peculiarities: cephalalgic, cerebral and cerebrospinal hypertensive syndrome, cognitive impairment, diffuse neurological symptoms, and pyramidal insufficiency prevailed in the clinical picture. Only in the main group were cases of a combination of three to eight neurological syndromes detected. A decrease in cognitive function was found in patients with repeated mild TBI compared to the control group according to neuropsychological testing. The analysis of cognitive evoked potentials revealed an increase in the latent period of the cognitive complex P300 in patients with repeated TBI compared with the control group, indicating a decrease in cognitive function. More frequent CP was detected in the main group. The use of modern neuroimaging methods revealed that patients with repeated TBI had increased width of the lateral ventricles on both sides, ventricle III, and the cavity of the septum compared with the control group, as well as a higher frequency of expansion of the septum and convexity of the subarachnoid spaces. Patients with repeated mild TBI are characterised by an increase in blood flow velocity in the extracranial parts of the carotid basin and a decrease in velocity in the vessels of the vertebrobasilar basin with a change in vascular resistance, in the segments of the intracranial part of the carotid basin — a decrease in blood flow velocity without a change in vascular resistance. Disorders of venous cerebral circulation (increased velocity in the internal jugular vein and Rosenthal veins) were recorded in the majority of the main group. According to the data of the CEG, in patients with repeated TBI against the background of diffuse changes in brain bioelectrical activity, focal changes in the left hemisphere of the brain are more common. Dominant arrhythmia was recorded in 97.78 % of patients in the main group. The amplitude of arrhythmia in patients with repeated TBI is lower compared to the control group, and the frequency of arrhythmic oscillations is higher. Conclusions. The use of clinical and diagnostic control allows to prevent the development of damage and obtain objective information about the state of the brain and its structures.

Investigation of renal perfusion and pathological changes in patients with acute kidney disease and tubulointerstitial nephritis using intravoxel incoherent motion and arterial spin labelling MRI: a prospective, observational study protocol

IntroductionAcute kidney injury (AKI) is a critical condition with a complex aetiology and different outcomes, where haemodynamic dysfunction, renal hypoperfusion and inflammation serve as key contributors to its development and...

The effect of diabetes mellitus on lumbar disc degeneration: an MRI-based study.

This study aims to analyse the effect of diabetes mellitus (DM) on the radiological changes of Magnetic Resonance Imaging (MRI) on the intervertebral discs and paravertebral muscle to investigate the effect of DM on spinal degeneration. This retrospective study initially included 262 patients who underwent treatment between January 2020 and December 2021 because of lumbar disc herniation. Amongst these patients, 98 patients suffered from type 2 diabetes mellitus (T2DM) for more than five years; this is the poorly controlled group (haemoglobin A1c (HbA1c) ≥ 6.5%; BMI: 26.28 ± 3.60; HbA1c: 7.5, IQR = 1.3). Another 164 patients without T2DM are included in the control group. The data collected and analysed include gender, age, smoking, alcohol use, disease course, Charlson Comorbidity Index, BMI, and radiological parameters including disc height, modified Pfirrmann grading scores, percentage of fat infiltration area of paravertebral muscle, and pathological changes of the endplate. After propensity score-matched analysis, the difference in general data between the control and T2DM groups was eliminated, and 186 patients were analysed. The modified Pfirrmann grading scores showed statistical differences in every lumbar segment, suggesting that the T2DM group suffered from greater disc degeneration at all L1-S1 segments compared with the control group. The disc height from L1/2 to L5/S1 was not statistically different between the two groups. Compared to the T2DM group, the control group had a lower percentage of fat infiltration areas in L4/5 and L5/S1 paravertebral muscle, whereas L1/2 to L3/4 showed no statistical difference. The T2DM group had more pathological changes of cartilage endplate compared with the control group. Prolonged uncontrolled hyperglycaemia may contribute to lumbar disc degeneration, fatty infiltration of the paraspinal muscles in the lower lumbar segments, and increased incidence of endplate cartilage pathological changes in patients with degenerative disc disease.

TSRNet: Tongue image segmentation with global and local refinement

Tongue Image Segmentation is an essential task for intelligent Traditional Chinese Medicine (TCM), as the tongue is sensitive to the physiological conditions and pathological changes of patients and can help physicians determine strategies for the syndrome differentiation. However, it is a big challenge to acquire an accurate tongue segmentation mask, due to the varied shape and texture of the tongue. This paper proposes a novel tongue segmentation network based on an encoder–decoder framework with global and local refinement, named TSRNet. In the global refinement module, we design an effective module for fusing features from an autoencoder, which is pre-trained on tongue images with segmentation labels, so that the network can make use of the prior knowledge. Moreover, in the local refinement module, we perform patch sampling according to the coarse prediction boundary and correct errors through a patch segmentation module. Both two modules are plugged into the decoder to obtain better tongue segmentation results by training end-to-end. Experimental results compared with state-of-the-art models on two real-world tongue datasets demonstrate the effectiveness of the proposed TSRNet.

Development of the prosencephalic structures, ganglionic eminence, basal ganglia and thalamus at 11 + 3 to 13 + 6 gestational weeks on 3D transvaginal ultrasound including normative data

ObjectivesTo show the development of ganglionic eminence, basal ganglia and thalamus/hypothalamus in week 11 + 3 to 13 + 6 by transvaginal 3D ultrasound.MethodsTo visualize the prosencephalic structures surrounding the 3rd ventricle, 285 three-dimensional ultrasound volume blocks from 402 fetuses examined were selected in a prospective transvaginal 3D study to compare ultrasound images of ganglionic eminence, basal ganglia, thalamus/hypothalamus with embryological sections. In addition, measurements of the described structures were made in 104 fetuses to quantify the embryological development.ResultsThe sonomorphologic characteristics of ganglionic eminence, basal ganglia and thalamus/hypothalamus are described in 71% of the fetuses examined. Measurements of the structures in 57% of the fetuses, show the following results: axGE ap = 0.17 + 0.112*CRL; axGE/I = 0.888 + 0.048*CRL; axGE/BG = 0.569 + 0.041*CRL; coGE/BG = 0.381 + 0.048*CRL; coTh lat = − 0.002 + 0.135*CRL; coTh/HyT = 3.68 + 0.059*CRL; co3.V lat = 0.54 + 0.008*CRL.ConclusionTransvaginal 3D neurosonography allows visualization and measurement of normal structures in the fetal prosencephalon at 11 + 3 to 13 + 6 weeks of gestation (GW) including details of ganglionic eminence (GE), basal ganglia (BG), and thalamus/hypothalamus (Th/HyT). Further scientific work is needed before using the results to decide on pathological changes in patients.

Comparison of sound touch elastography and quantification for assessing the renal pathologic changes in patients with proteinuria

ObjectiveSound touch elastography (STE) and sound touch quantification (STQ) are novel imaging methods to evaluate tissue stiffness. This study aims to investigate renal stiffness in patients with chronic kidney disease (CKD) by STE and STQ, using renal biopsy as ‘gold standard’.MethodsBetween 2019 January and 2022 June, 60 patients who underwent renal biopsy for proteinuria (cases) and 45 healthy volunteers (controls) at our hospital were included in this study. The maximum and mean elastic modulus (Emax, Emean) of region of interest in right kidney were measured by STE and STQ techniques. Biochemical profiles and renal biopsy findings were recorded.ResultsBoth Emax and Emean measured by STE were significantly different between cases and controls. ROC analysis of STE measurements revealed using a cutoff of 13.53 kPa for Emax and 10.16 kPa for Emean, the area under the curve (AUC) to distinguish nephropathy from healthy was 0.718 and 0.744. Analysis of ROC for STQ measurements showed that using a cutoff value of 15.87 kPa for Emax and 9.95 kPa for Emean, the AUC for the nephropathy was 0.612 and 0.569. Emax and Emean values were significantly different among CKD patients with mild, moderate and severe pathological stage. The Emax value for STE was positively related to Scr, β2-MG (r = 0.257, 0.292, p < 0.05).ConclusionBoth STE and STQ are non-invasive, feasible methods to quantitatively evaluate renal stiffness. STE is more effective than STQ in the diagnosis of CKD patients with proteinuria.Critical relevance statementSound touch elastography is more effective than sound touch quantification in the diagnosis of chronic kidney disease patients with proteinuria.Key points• Emax and Emean measured by STE were different between cases and controls.• Emax and Emean were different among CKD patients with different pathological stages.• The Emax value for STE was positively related to serum creatinine, β2-microglobulinGraphical

Bowman’s capsule rupture and the Oxford MEST-C score in adult patients with Immunoglobulin a vasculitis nephritis: a single center experience

Objective Bowman’s capsule rupture (BCR) is a glomerular pathological change, but it is still not well recognized in immunoglobulin A vasculitis nephritis (IgAV-N). The Oxford MEST-C score is a classification for IgA nephropathy; however, its clinical correlation and prognostic value in adult patients with IgAV-N are unclear. Methods A retrospective study of 145 adult patients with IgAV-N diagnosed by renal biopsy was conducted. Clinical manifestations, pathological changes and the prognosis of IgAV-N patients were compared depending on the presence or absence of BCR, International Study of Kidney Disease in Children (ISKDC) classification and MEST-C score. The primary endpoint events were end-stage renal disease, renal replacement therapy and all-cause death. Results In total, 51 of 145 (35.17%) patients with IgAV-N presented with BCR. Patients with BCR had more proteinuria, lower serum albumin, and more crescents. Compared with IgAV-N patients with crescents only, 51/100 patients with crescents combined with BCR had a higher proportion of crescents in all glomeruli (15.79% vs. 9.09%; p = 0.003). Patients with higher ISKDC grades had more severe clinical presentation, but it did not reflect the prognosis. However, the MEST-C score not only reflected clinical manifestations but also predicted prognosis (p < 0.05). BCR contributed to the effectiveness of the MEST-C score in predicting the prognosis of IgAV-N (C-index: 0.845 to 0.855). Conclusions BCR is associated with clinical manifestations and pathological changes in patients with IgAV-N. The ISKDC classification and MEST-C score are related to the patient’s condition, but only the MEST-C score is correlated with the prognosis of patients with IgAV-N, while BCR can improve its predictive ability.

Insights into Advanced Neurological Dysfunction Mechanisms Following DBS Surgery in Parkinson's Patients: Neuroinflammation and Pyroptosis.

Parkinson's disease is a severe neurodegenerative disorder. Currently, deep brain electrical stimulation (DBS) is the first line of surgical treatment. However, serious neurological impairments such as speech disorders, disturbances of consciousness, and depression after surgery limit the efficacy of treatment. In this review, we summarize the recent experimental and clinical studies that have explored the possible causes of neurological deficits after DBS. Furthermore, we tried to identify clues from oxidative stress and pathological changes in patients that could lead to the activation of microglia and astrocytes in DBS surgical injury. Notably, reliable evidence supports the idea that neuroinflammation is caused by microglia and astrocytes, which may contribute to caspase-1 pathway-mediated neuronal pyroptosis. Finally, existing drugs and treatments may partially ameliorate the loss of neurological function in patients following DBS surgery by exerting neuroprotective effects.

WCN23-0223 CLINICAL AND PATHOLOGICAL CHANGES IN PATIENTS WITH IgA NEPHROPATHY-A PROSPECTIVE COHORT STUDY FROM INDIA

WCN23-0223 CLINICAL AND PATHOLOGICAL CHANGES IN PATIENTS WITH IgA NEPHROPATHY-A PROSPECTIVE COHORT STUDY FROM INDIA

The potential reversibility of Cutibacterium acnes-related disc degeneration: a rabbit model

The most prominent pathological changes in patients with low back pain include Modic changes and degeneration of intervertebral discs. Presence of Cutibacterium acnes (C. acnes) and formation of biofilms have been linked to endplate changes and disc degeneration [ 1 Dudli S Liebenberg E Magnitsky S Miller S Demir-Deviren S Lotz JC. Propionibacterium acnes infected intervertebral discs cause vertebral bone marrow lesions consistent with Modic changes. J Orthop Res. 2016 Aug; 34: 1447-1455 Crossref PubMed Scopus (55) Google Scholar , 2 Georgy M Stern M Murphy K. What Is the Role of the Bacterium Propionibacterium acnes in Type 1 Modic Changes? A Review of the Literature. Can Assoc Radiol J. 2017 Nov; 68: 419-424 Crossref PubMed Scopus (13) Google Scholar , 3 Manniche C O'Neill S New insights link low-virulent disc infections to the etiology of severe disc degeneration and Modic changes. Future Sci OA. 2019 Mar 18; 5: FSO389 Crossref PubMed Scopus (10) Google Scholar , 4 Shan Z Zhang X Li S Yu T Liu J Zhao F. Propionibacterium acnes Incubation in the Discs Can Result in Time-Dependent Modic Changes: A Long-Term Rabbit Model. Spine (Phila Pa 1976). 2017 Nov 1; 42: 1595-1603 Crossref PubMed Scopus (14) Google Scholar ]. The aim of the current pilot was to test a minimally invasive model of disc degeneration and a potential of anti-bacterial biologic to reverse disc degeneration caused by C. acnes.

Erxian decoction inhibits apoptosis by activating Akt1 and repairs spinal cord injury in rats

ObjectiveSpinal cord injury (SCI) often leads to severe physiological and pathological changes in patients. Erxian Decoction (EXD) is effective in the postoperative treatment of spinal cord injury, but its specific mechanism of action is poorly defined. MethodsNetwork pharmacology and molecular docking were used to predict the potential mechanisms of EXD in SCI. In vivo studies were used to validate the above predictions. For in vivo study, the rats were pretreated with or without EXD (5.76 g/kg, by intragastric gavage). Multiple molecular biological test methods to identify molecular mechanisms. One-way analysis of variance (ANOVA) was used with Bonferroni's post-hoc test to identify the differences between groups. ResultsIn vivo studies have shown that EXD improved motor function at 7dpi in SCI rats (P < 0.0001), significantly reduced spinal cord edema (P = 0.0139), upregulated 5-HT, GFAP, and TMEM119 expression. Through network pharmacology analysis, we found that Akt1 in EXD plays a role in treating SCI. The underlying mechanism may be the inhibition of apoptosis after activation of Akt1 phosphorylation. Molecular docking revealed that the key compounds could spontaneously bind to the Akt1 protein. Pharmacological inhibition of Akt1 activation by MK-2206, attenuated the anti-apoptotic effect of EXD on SCI in rats (P < 0.0001). ConclusionsEXD inhibits apoptosis by activating Akt1, reduce spinal cord edema and restore behavioral function after SCI in rats.

Influence of zinc levels and Nrf2 expression in the clinical and pathological changes in patients with diabetic nephropathy

ObjectiveWe investigated the correlation between zinc levels and Nrf2 expression and potential effects on the clinicopathology of patients with diabetic nephropathy (DN).MethodsWe selected 30 patients with DN, diagnosed via renal biopsy at our hospital from March 2018 to November 2019, and enrolled 30 healthy individuals from a medical examination center as the control group. Patients with DN were divided into normal-zinc and low-zinc groups. We detected the levels of zinc, copper, and Nrf2 mRNA in their serum, and collected the clinical and pathological data of DN patients.ResultsSerum zinc level and Nrf2 mRNA expression were significantly decreased in patients with DN compared to those of healthy people (P < 0.05). Of the 30 patients, 16 had low zinc (53.3%) and 14 had normal zinc levels (46.7%). There was no significant difference in the blood Nrf2 mRNA expression between the two groups (P > 0.05). However, the expression of Nrf2 in the kidney tissue of the low-zinc group was significantly lower compared to the normal-zinc group (P < 0.05). Diastolic blood pressure and copper levels were significantly higher in the low-zinc group (P < 0.05). In contrast, body mass index, red blood cell count, Hb level, and the ratio of zinc to copper were significantly lower in the low-zinc group (P < 0.05). The pathological classifications of the low-zinc group were more severe (P < 0.05).ConclusionPatients with DN were more likely to have zinc deficiency and lower expression of Nrf2. Additionally, DN patients with zinc deficiency were prone to have more severe clinical and pathological manifestations.

Crescents, an Independent Risk Factor for the Progression of Type 2 Diabetic Kidney Disease.

Crescents have been noticed in pathologic changes in patients with diabetic kidney disease (DKD). However, the clinical significance of crescents is still not well recognized. The main objective was to investigate the association between crescents and the prognoses of type 2 DKD (T2DKD) patients, and, secondly, to analyze the relationship between crescents and clinicopathologic features. A retrospective cohort study of 155 patients with T2DKD diagnosed by renal biopsy was carried out in a single center. Clinicopathologic features of patients with or without crescents were analyzed. Cox regression models and meta-analysis were used to determine the prognostic values of crescents for T2DKD. A nomogram was constructed to provide a simple estimation method of 1, 3, and 5-year renal survival for patients with T2DKD. Compared with T2DKD patients without crescents, patients with crescents had higher 24-hour proteinuria and serum creatinine levels, as well as more severe Kimmelstiel-Wilson (K-W) nodules, segmental sclerosis (SS), and mesangiolysis (all P < .05). Furthermore, the crescents were positively correlated with serum creatinine, 24-hour proteinuria, K-W nodules, SS, mesangiolysis, and complement 3 deposition. Multivariate Cox models showed that crescents were an independent prognostic risk factor for renal survival (hazard ratio [HR] 2.68, 95% CI 1.27-5.64). The meta-analyzed results of 4 studies on crescents in T2DKD confirmed that patients with crescents had a significantly higher HR for renal progression. Patients with crescents in T2DKD have more severe clinicopathologic changes and worse prognoses. The crescent can serve as an independent risk factor for T2DKD progression.

Cardiac macrophage density in Covid-19 infection: relationship to myocyte necrosis and acute lung injury

SARS-Cov-2 infection is not limited to the respiratory tract and can involve other organs including the heart, blood vessels, kidneys, liver, gastrointestinal tract, placenta, and skin. Covid-19 patients with cardiac involvement usually have higher morbidity and mortality compared to those without cardiac involvement. The frequency and the specificity of the myocardial pathological changes in patients who die after documented infection with SARS-Cov-2 is uncertain. Macrophages can be found in the normal heart (interstitium, around the endothelial cells and in the epicardial adipose tissue), and they are considered part of the major immune cell population in the heart. In this case-control autopsy study, we compare the gross and microscopic cardiac findings, and the available clinical characteristics between a group of 10 Covid-19 decedents and a control group of 20 patients who died with non-SARS-Cov-2 severe bronchopneumonia and/or diffuse alveolar damage. The objectives of this semi-quantitative study are to study single myocyte necrosis and its relation to the strain on the heart caused by lung injury as a causative mechanism, and to study the density of myocardial and epicardial macrophages in Covid-19 hearts in comparison to the control group, and in Covid-19 hearts with single myocyte necrosis in comparison to Covid-19 hearts without single myocyte necrosis. Lymphocytic myocarditis was not identified in any of the hearts from the Covid-19 or the control group. Single myocyte necrosis is more frequent in the Covid-19 group compared to the control group, suggesting that it is unrelated to the strain on the heart caused by underlying lung injury. The density of the macrophages in the epicardium and myocardium in the hearts of the Covid-19 group is higher compared to those in the control group. The density of epicardial macrophages is higher in the Covid-19 hearts with single myocyte necrosis than in those without. These observations contribute to our increasing appreciation of the role of macrophages in the pathophysiologic response to infection by SARS-CoV-2.

Altered pain sensitivity in 5×familial Alzheimer disease mice is associated with dendritic spine loss in anterior cingulate cortex pyramidal neurons.

Chronic pain is highly prevalent. Individuals with cognitive disorders such as Alzheimer disease are a susceptible population in which pain is frequently difficult to diagnosis. It is still unclear whether the pathological changes in patients with Alzheimer disease will affect pain processing. Here, we leverage animal behavior, neural activity recording, optogenetics, chemogenetics, and Alzheimer disease modeling to examine the contribution of the anterior cingulate cortex (ACC) neurons to pain response. The 5× familial Alzheimer disease mice show alleviated mechanical allodynia which can be regained by the genetic activation of ACC excitatory neurons. Furthermore, the lower peak neuronal excitation, delayed response initiation, as well as the dendritic spine reduction of ACC pyramidal neurons in 5×familial Alzheimer disease mice can be mimicked by Rac1 or actin polymerization inhibitor in wild-type (WT) mice. These findings indicate that abnormal of pain sensitivity in Alzheimer disease modeling mice is closely related to the variation of neuronal activity and dendritic spine loss in ACC pyramidal neurons, suggesting the crucial role of dendritic spine density in pain processing.

Multimarker synaptic protein cerebrospinal fluid panels reflect TDP-43 pathology and cognitive performance in a pathological cohort of frontotemporal lobar degeneration

BackgroundSynapse degeneration is an early event in pathological frontotemporal lobar degeneration (FTLD). Consequently, a surrogate marker of synapse loss could be used to monitor early pathologic changes in patients with underlying FTLD. The aim of this study was to evaluate the relationship of antemortem cerebrospinal fluid (CSF) levels of 8 synaptic proteins with postmortem global tau and TDP-43 burden and cognitive performance and to assess their diagnostic capacity in a neuropathological FTLD cohort.MethodsWe included patients with a neuropathological confirmation of FTLD-Tau (n = 24, mean age-at-CSF 67 years ± 11), FTLD-TDP (n = 25, 66 years ± 9) or AD (n = 25, 73 years ± 6) as well as cognitively normal controls (n = 35, 69 years ± 7) from the Penn FTD Center and ADRC. We used a semi-quantitative measure of tau and TDP-43 inclusions to quantify pathological burden across 16 brain regions. Statistical methods included Spearman rank correlations, one-way analysis of covariance, ordinal regression, step-wise multiple linear regression and receiver-operating characteristic curves.ResultCSF calsyntenin-1 and neurexin-2a were correlated in all patient groups (rs = .55 to .88). In FTLD-TDP, we observed low antemortem CSF levels of calsyntenin-1 and neurexin-2a compared to AD (.72-fold, p = .001, .77-fold, p = .04, respectively) and controls (.80-fold, p = .02, .78-fold, p = .02, respectively), which were inversely associated with post-mortem global TDP-43 burden (regression r2 = .56, p = .007 and r2 = .57, p = .006, respectively). A multimarker panel including calsyntenin-1 was associated with TDP-43 burden (r2 = .69, p = .003) and MMSE score (r2 = .19, p = .03) in FTLD. A second multimarker synaptic panel, also including calsyntenin-1, was associated with MMSE score in FTLD-tau (r2 = .49, p = .04) and improved diagnostic performance to discriminate FTLD-Tau and FTLD-TDP neuropathologic subtypes (AUC = .83).ConclusionThese synaptic panels have potential in the differential diagnosis of FTLD neuropathologic subtypes and as surrogate markers of cognitive performance in future clinical trials targeting TDP-43 or tau.