Reversal of cardiac and renal damage in a teenager with hypertension: A case report.

The authors describe the case of a 16-year-old male who was incidentally found to have a blood pressure of 200/? mmHg 6 months previously due to blurred vision and was diagnosed with "high risk of hypertension grade 3, renal insufficiency, hypertensive encephalopathy, hypertensive heart disease, and fundus hemorrhage" after relevant examinations were performed. His blood pressure fluctuated around 120/90 mmHg after beginning antihypertensive treatment. While the diagnostic work-up of his hypertension was inconclusive, he had severe hypertension with brachydactyly type E and short stature on physical examination. The patient's cardiac damage and renal insufficiency ultimately returned to normal after strict blood pressure control, suggesting that hypertension and brachydactyly syndrome alone do not cause cardiac and renal damage.

A pan-cancer analysis of potassium channel tetramerization domain containing 12 in human cancer.

Abnormal expression of the potassium channel tetramerization domain containing 12 (KCTD12) is closely related to the occurrence and development of various tumors, but a pan-cancer analysis of KCTD12 has not yet been conducted. We explored the association between KCTD12 and more than 30 human malignancies using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. First, the mRNA and protein levels of KCTD12 were examined and their correlations with tumor stage and survival were explored. Second, we analyzed the infiltration of CD8+ and CD4+ T cells and cancer-associated fibroblasts in tumors and explored the correlation between KCTD12 expression and tumor cell stemness, genomic heterogeneity, and diagnostic specificity. Finally, we explored the molecular mechanisms associated with KCTD12 using KEGG/GO analysis. The results showed that KCTD12 mRNA and protein expression levels decreased in most tumors was significantly associated with the prognosis of tumor patients, and the phosphorylation level of KCTD12 decreased in several tumors, such as S200 and T196, pancreatic adenocarcinoma (PAAD), lung adenocarcinoma (LUAD), and breast invasive cancer (BRCA). The expression of KCTD12 was positively correlated with the degree of cancer-associated fibroblasts infiltration in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), head and neck squamous cell carcinoma (HNSC), PAAD, and stomach adenocarcinoma (STAD). The relationship between KCTD12 expression and CD8+ and CD4+ T cell infiltration was also clarified. KCTD12 showed high diagnostic sensitivity for various types of tumors and may be involved in tumor cell biology by affecting tumor cell stemness, tumor burden, and other characteristics. Finally, we analyzed the molecular functions of KCTD12 and possible KEGG/GO signaling pathways. In this study, we developed a biological marker for diagnosis, prognosis, and immune infiltration of the pan-cancers.

HIF-1α-PPARγ-mTORC1 signaling pathway-mediated autophagy induces inflammatory response in pancreatic cells in rats with hyperlipidemic acute pancreatitis.

OBJECTIVE: The incidence of hyperlipidemic acute pancreatitis (HLAP) has rapidly increased in recent years in China. Autophagy has been implicated in the inflammatory response of pancreatic cells in HLAP, but the molecular mechanisms remain unclear. METHODS: In this study, the role of HIF-1α-PPARγ-mTORC1 pathway-mediated autophagy in the inflammatory response of pancreatic cells and the underlying molecular mechanism were investigated in a rat model of HLAP using immunohistochemistry, ELISA, electron microscopy, and western blot analysis. RESULTS: The results revealed that autophagy was significantly increased and pancreatic injury was exacerbated in HLAP rats, and the inflammatory response was further exacerbated by treatment with rapamycin but relieved by treatment with 3-MA. Hyperlipidemia induced upregulation of HIF-1α and downregulation of PPARγ, which in turn led to an increase in autophagy and consequently exacerbation of the inflammatory response of pancreatic cells. CONCLUSIONS: HIF-1α-PPARγ-mTORC1 pathway-mediated autophagy plays a critical role in the inflammatory response of pancreatic cells in HLAP, and interference with the HIF-1α-PPARγ-mTOR pathway can serve as a new strategy for the prevention and treatment of HLAP.

Effects of four disease-controlling agents (chlorothalonil, CuCl2, harpin, and melatonin) on postharvest jujube fruit quality.

Postharvest senescence and disease development can reduce the nutritional value of fresh jujube fruit. Herein, four different disease-controlling agents (chlorothalonil, CuCl2, harpin and melatonin) were separately applied to fresh jujube fruit, and all improved postharvest quality (evaluated by disease severity, antioxidant accumulation and senescence) relative to controls. Disease severity was drastically inhibited by these agents, in the order chlorothalonil > CuCl2 > harpin > melatonin. However, chlorothalonil residues were detected even after storage for 4 weeks. These agents increased the activities of defense enzymes including phenylalanine ammonia-lyase, polyphenol oxidase, glutathione reductase and glutathione S-transferase, as well as accumulation of antioxidant compounds such as ascorbic acid, glutathione, flavonoids and phenolics, in postharvest jujube fruit. The enhanced antioxidant content and antioxidant capacity (evaluated by Fe3+ reducing power) was ordered melatonin > harpin > CuCl2 > chlorothalonil. All four agents significantly delayed senescence (evaluated by weight loss, respiration rate and firmness), with the effect ordered CuCl2 > melatonin > harpin > chlorothalonil. Moreover, treatment with CuCl2 also increased copper accumulation ~ threefold in postharvest jujube fruit. Among the four agents, postharvest treatment with CuCl2 could be considered most appropriate for improving postharvest jujube fruit quality under low temperature conditions without sterilization.

Antiphosphatidylserine/prothrombin antibodies (aPS/PT) and risk of obstetric anti-phospholipid syndrome.

OBJECTIVE: Assessment of the prevalence of anti-phosphatidylserine-prothrombin antibodies (aPS/PT) with OAPS and SN-OAPS in Chinese patients. METHODS: This retrospective study proceeded at Ren Ji Hospital, Shanghai, China, from January 2019 to January 2020. Two hundred eleven OAPS, 68 SN-OAPS, 81 disease controls, and 30 healthy donors were enrolled. IgM and IgG aPS/PT, IgM/IgG - aCL, and IgM/ IgG/ anti-ß2GPI antibodies were tested by ELISA while LAC was tested by clotting assays. All the patients were followed up and tested at least twice over 12 weeks apart. RESULTS: Thirty-three OAPS (15.64%) and 31 SN-OAPS (45.59%) were positive for aPS/PT. aPS/PT IgM showed a high Youden index (.813), which classified OAPS and SN-OAPS patients from healthy controls and other autoimmune diseases. aPS/PT showed a stronger relationship with LAC. Of the 25 OAPS women positive for IgM aPS/PT, 19 (79%) LAC were positive, while of the eight women positive for IgG aPS/PT, 100% were found LAC positive. CONCLUSION: aPS/PT antibody showed an efficient diagnostic value for Chinese patients with OAPS and SN-OAPS, which could be a potential risk predictor for obstetric complications.

Multi-Information Model for Large-Flowered Chrysanthemum Cultivar Recognition and Classification.

The traditional Chinese large-flowered chrysanthemum is one of the cultivar groups of chrysanthemum (Chrysanthemum × morifolium Ramat.) with great morphological variation based on many cultivars. Some experts have established several large-flowered chrysanthemum classification systems by using the method of comparative morphology. However, for many cultivars, accurate recognition and classification are still a problem. Combined with the comparative morphological traits of selected samples, we proposed a multi-information model based on deep learning to recognize and classify large-flowered chrysanthemum. In this study, we collected the images of 213 large-flowered chrysanthemum cultivars in two consecutive years, 2018 and 2019. Based on the 2018 dataset, we constructed a multi-information classification model using non-pre-trained ResNet18 as the backbone network. The model achieves 70.62% top-5 test accuracy for the 2019 dataset. We explored the ability of image features to represent the characteristics of large-flowered chrysanthemum. The affinity propagation (AP) clustering shows that the features are sufficient to discriminate flower colors. The principal component analysis (PCA) shows the petal type has a better interpretation than the flower type. The training sample processing, model training scheme, and learning rate adjustment method affected the convergence and generalization of the model. The non-pre-trained model overcomes the problem of focusing on texture by ignoring colors with the ImageNet pre-trained model. These results lay a foundation for the automated recognition and classification of large-flowered chrysanthemum cultivars based on image classification.

Application of Immersive Virtual-Reality-Based Puzzle Games in Elderly Patients with Post-Stroke Cognitive Impairment: A Pilot Study.

Background: The society is aging in China, and the cognitive level of elderly post-stroke patients gradually declines. Face-to-face cognitive functional training is no longer sufficient. Immersive virtual reality (IVR) is a promising rehabilitation training device. In this study, we developed an IVR-based puzzle game to explore its effectiveness, feasibility, and safety in elderly stroke patients with cognitive dysfunction. Methods: A total of 30 patients with mild post-stroke cognitive impairment after stroke were randomly assigned to a control or IVR group. Patients in both groups received routine rehabilitation therapy. Patients in the control group received traditional cognitive training, and those in the IVR group received IVR-based puzzle game therapy. Before and after treatment, Montreal cognitive assessment (MOCA), trail-making test-A (TMT-A), digit symbol substitution test (DSST), digital span test (DST), verbal fluency test (VFT), and modified Barthel index (MBI) were evaluated in both groups. In addition, the IVR group was administered a self-report questionnaire to obtain feedback on user experience. Results: There was no significant difference in the baseline data between the two groups. After six weeks of treatment, the cognitive assessment scores were improved in both groups. Moreover, the IVR group showed more improvements than the control group in the DSST (Z = 2.203, p = 0.028 < 0.05, η2 = 0.16); MOCA (T = 1.186, p = 0.246 > 0.05, d = 0.44), TMT-A (T = 1.791, p = 0.084 > 0.05, d = 0.65), MBI (T = 0.783, p = 0.44 > 0.05, d = 0.28), FDST (Z = 0.78, p = 0.435 > 0.05, η2 = 0.02), BDST (Z = 0.347, p = 0.728 > 0.05, η2 = 0.004), and VFT(Z = 1.087, p = 0.277 > 0.05, η2 = 0.039) did not significantly improve. The significant difference in DSST represents an improvement in executive function and visual−spatial cognitive characteristics. The other assessment scores did not show such features. Therefore, we did not observe significant differences through this measure. According to the results of the self-report questionnaire, most of the patients were satisfied with the equipment stability and training content. Several individuals reported mild adverse reactions. Conclusions: This pilot study suggests that IVR-based puzzle games are a promising approach to improve post-stroke cognitive function, especially executive cognitive function, and visual−spatial attention in older adults.

Association Between Serum C1q Tumor Necrosis Factor-Related Protein 9 and the Clinical Characteristics and Prognosis of Ischemic Stroke.

INTRODUCTION: C1q tumor necrosis factor (TNF)-related protein 9 (CTRP9) is a novel member of the C1q/TNF superfamily. According to our previous review, CTRP9 plays a vital role in the process of cardiovascular diseases, including regulating energy metabolism, modulating vasomotion, protecting endothelial cells, inhibiting platelet activation, inhibiting pathological vascular remodeling, stabilizing atherosclerotic plaques, and protecting the heart. We proposed that CTRP9 could play multiple positive and beneficial roles in vascular lesions in ischemic stroke (IS). Here, we aimed to study the relationship between serum CTRP9 and the etiology, severity, and prognosis of IS patients. METHODS: A total of 302 patients with IS and 173 non-stroke controls were selected from the same hospital, and all patients with IS were followed up 12 months after stroke onset. Stroke etiology was classified according to the Trial of ORG 10172 in Acute Stroke Treatment classification. Symptomatic severity was determined using the National Institutes of Health Stroke Scale score. The lesion volume of acute cerebral ischemia was measured using magnetic resonance imaging (MRI). The unfavorable functional outcome was a combination of death or major disability 12 months after stroke onset. Receiver operating characteristic (ROC) curves and integrated discrimination improvement (IDI) and net reclassification improvement (NRI) statistics were applied in the statistical analysis. RESULTS: We found that serum CTRP9 levels and the ratios of CTRP9/total cholesterol (TC), CTRP9/triglyceride (TG), CTRP9/low-density lipoprotein cholesterol (LDL-C), and CTRP9/high-density lipoprotein cholesterol (HDL-C) were associated with the presence of IS. Moreover, the serum CTRP9 concentration was positively associated with the severity of IS. Incorporation of CTRP9/LDL-C levels into a fully adjusted model for IS-cardioembolic (CE) improved discrimination and calibration, and significantly improved reclassification. In addition, CTRP9 was a predictor of unfavorable functional outcomes. CONCLUSIONS: All the findings indicated that serum CTRP9 could be a promising blood-derived biomarker for the early evaluation and prognosis assessment of IS. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800020330.

Prognostic analysis of antibody typing and treatment for antiphospholipid syndrome-related recurrent spontaneous abortion.

OBJECTIVE: To determine the efficacy of antibody typing and treatment on live birth rate in Chinese patients with antiphospholipid syndrome (APS)-related recurrent spontaneous abortion (RSA). METHODS: A retrospective study analyzed 4542 Chinese patients who experienced spontaneous abortion, of whom 314 had APS (272 primary and 42 secondary). Type of antibodies was tested. Anticoagulant and anti-inflammatory treatments were adopted according to the titer and type of antibodies. The incidence of repeated abortion and placental dysfunction, gestational age, and mean weight of the fetuses were recorded. RESULTS: Among the patients with APS-related RSA, primary APS accounted for the largest proportion. The proportion of antibody classification was as follows: ß2-glycoprotein 1 (ß2GP1)-IgM (151, 48.08%), lupus anticoagulant (LAC) (36, 11.46%), anticardiolipin (aCL)-IgM (32, 10.19%), ß2GP1-IgM and aCL-IgM (29, 9.23%), and aCL-IgG (16, 5.09%). After treatment, the negative conversion of antibody, including ß2GP1-IgM and LAC, significantly improved pregnancy outcomes. There was no significant difference in pregnancy outcomes between the other antibody titers. CONCLUSION: The combination of anticoagulant and anti-inflammatory treatment led to a higher live birth rate in the treatment of APS-related RSA, highlighting the potential of antibody typing in providing clinical guidance for the treatment of APS-related RSA.

Associations between Upper Extremity Motor Function and Aphasia after Stroke: A Multicenter Cross-Sectional Study.

METHODS: Patients with stroke were compared and correlated from overall and three periods (1-3 months, 4-6 months, and >6 months). Fugl-Meyer assessment for the upper extremity (FMA-UE) and action research and arm test (ARAT) were used to compare the UE motor status between patients with PSA and without PSA through a cross-sectional study among 435 patients. Then, the correlations between the evaluation scale scores of UE motor status and language function of patients with PSA were analyzed in various dimensions, and the language subfunction most closely related to UE motor function was analyzed by multiple linear regression analysis. RESULTS: We found that the scores of FMA-UE and ARAT in patients with PSA were 14 points ((CI) 10 to 18, p < 0.001) and 11 points lower ((CI) 8 to 13, p < 0.001), respectively, than those without PSA. Their FMA-UE (r = 0.70, p < 0.001) and ARAT (r = 0.62, p < 0.001) scores were positively correlated with language function. Regression analysis demonstrated that spontaneous speech ability may account for UE motor function (R 2 = 0.51, p < 0.001; R 2 = 0.42, p < 0.001). Consistent results were also obtained from the analyses within the three time subgroups. CONCLUSION: Stroke patients with PSA have worse UE motor performance. UE motor status and language function showed positive correlations, in which spontaneous speech ability significantly accounts for the associations.

Blood-Based Biomarkers: A Forgotten Friend of Hyperacute Ischemic Stroke.

Ischemic stroke (IS) is the second leading cause of death worldwide. Multimodal neuroimaging techniques that have significantly facilitated the diagnosis of hyperacute IS are not widely used in underdeveloped areas and community hospitals owing to drawbacks such as high cost and lack of trained operators. Moreover, these methods do not have sufficient resolution to detect changes in the brain at the cellular and molecular levels after IS onset. In contrast, blood-based biomarkers can reflect molecular and biochemical alterations in both normal and pathophysiologic processes including angiogenesis, metabolism, inflammation, oxidative stress, coagulation, thrombosis, glial activation, and neuronal and vascular injury, and can thus provide information complementary to findings from routine examinations and neuroimaging that is useful for diagnosis. In this review, we summarize the current state of knowledge on blood-based biomarkers of hyperacute IS including those associated with neuronal injury, glial activation, inflammation and oxidative stress, vascular injury and angiogenesis, coagulation and thrombosis, and metabolism as well as genetic and genomic biomarkers. Meanwhile, the blood sampling time of the biomarkers which are cited and summarized in the review is within 6 h after the onset of IS. Additionally, we also discuss the diagnostic and prognostic value of blood-based biomarkers in stroke patients, and future directions for their clinical application and development.

Parabiosis modeling: protocol, application and perspectives.

Parabiosis is a surgical method of animal modeling with a long history. It has been widely used in medical research, particularly in the fields of aging, stem cells, neuroscience, and immunity in the past two decades. The protocols for parabiosis have been improved many times and are now widely accepted. However, researchers need to consider many details, from surgical operation to perioperative management, to reduce mortality and maintain the parabiosis union. Although parabiosis has certain inevitable limitations, it still has broad application prospects as an irreplaceable animal model in the medical research field.

Association between infectious burden and cerebral microbleeds: a pilot cross-sectional study.

OBJECTIVE: Cerebral microbleeds (CMBs) is a subtype of cerebral small vessel disease. Their underlying pathogenesis remains unclear. The aim of this study was to investigate the association between infectious burden (IB) and CMBs. METHODS: Seven hundred and seventy-three consecutive patients who were hospitalized in the Department of Neurology in General Hospital of Western Theater Command without severe neurological symptoms were recruited and selected in this pilot cross-sectional study. CMBs were assessed using the susceptibility-weighted imaging sequence of magnetic resonance imaging. Immunoglobulin G antibodies against common pathogens, including herpes simplex virus (HSV)-1, HSV-2, cytomegalovirus (CMV), Chlamydia pneumoniae (C. pneumoniae), Mycoplasma pneumoniae (M. pneumoniae), Epstein-Barr virus (EBV), Helicobacter pylori (HP), and Borrelia burgdorferi (B. burgdorferi), were measured by commercial ELISA assays. IB was defined as a composite serologic measure of exposure to these common pathogens. RESULTS: Patients with and without CMBs were defined as the CMBs group (n = 76) and the non-CMBs group (n = 81), respectively. IB was significantly different between the CMBs and non-CMBs groups. After adjusted for other risk factors, the increased IB was independently associated with the presence of CMBs (P = 0.031, OR = 3.00, 95% CI [1.11-8.15]). IB was significantly positively associated with the number of CMBs (Spearman ρ = 0.653, P < 0.001). The levels of serum inflammatory markers were significantly different between the CMBs and non-CMBs groups and among the categories of IB. INTERPRETATION: IB consisting of HSV-1, HSV-2, CMV, C. pneumoniae, M. pneumoniae, EBV, HP, and B. burgdorferi was associated with CMBs. All the findings suggested that pathogen infection could be involved in the pathogenesis of CMBs.

Long non-coding RNA CASC2 induces apoptosis and autophagy in human colon cancer cells via modulation of TRIM16 expression.

Long non-coding RNAs (LncRNAs) have been shown to be involved in diverse cellular and physiological processes. Recent studies have proved their potential as the prospective therapeutic targets for cancer treatment. Herein, we examined the role of LncRNA CASC2 in human colon cancer. The gene expression analysis showed that LncRNA CASC2 is significantly suppressed in colon cancer tissues and cell lines. The immunohistochemistry also showed considerable increase of the Ki67 in colon cancer tissues suggestive of their aggressiveness. Overexpression of CASC2 inhibited the growth of HT-29 cells. The inhibition of HT-29 growth was due to the induction of apoptosis which was accompanied by upsurge of Bax, depletion of Bcl-2 and activation of caspase-3 cleavage. Electron microscopic analysis showed CASC2 overexpression also induced autophagy in the HT-29 cells which was associated with increase in LC3B II and Beclin 1 expression. Bioinformatic approaches and dual luciferase assay showed that CASC2 controls the TRIM16 via microRNA-214 axis. TRIM16 was found to be overexpressed in all the colon cancer tissues and cell lines. Overexpression of CASC2 caused significant inhibition of TRIM16. Additionally, silencing of TRIM16 resulted in the inhibition of HT-29 cell growth similar to that of CASC2 overexpression. Taken together, CASC2 may prove to be an important therapeutic target for colon cancer treatment.

Low-dose aspirin improves endometrial receptivity in the midluteal phase in unexplained recurrent pregnancy loss.

OBJECTIVE: To evaluate differences in Doppler parameters and pregnancy outcomes, if any, and to determine the predictive accuracy of such indices, as well as the effects of low-dose aspirin (LDA) in unexplained recurrent pregnancy loss (URPL). METHODS: An observational study was conducted at Ren Ji Hospital, Shanghai, China, from May 2015 to December 2016. The endometrial thickness, and the pulsatility index (PI), resistive index (RI), and systolic-to-diastolic ratio (S/D) values of endometrial and uterine artery blood flow were collected. Receiver operating characteristic (ROC) curve analysis was used to analyze data from URPL patients (three or more first-trimester spontaneous abortions with unknown etiology) and patients with normal fertility. A second ultrasonography examination was performed in URPL patients who had received daily LDA for 2 months. RESULTS: There were 190 URPL patients and 35 control patients. Endometrial thickness was significantly thinner in URPL patients than control patients (P=0.005). The PI, RI, and S/D values for endometrial blood flow and the mean PI, RI, and S/D values for uterine arteries were significantly higher in URPL patients (P<0.001). The predictive accuracy of the indices mentioned above were 0.660, 0.802, 0.852, 0.837, 0.784, 0.929, and 0.929, respectively. Following LDA supplementation, URPL patients showed a significant reduction in resistance to endometrial and uterine artery blood flow (P<0.001). CONCLUSION: URPL patients had impaired uterine perfusion. Doppler parameters are valuable in predicting women at high risk of URPL. LDA could be effective in improving endometrial receptivity.

Spatial distribution of IL4 controls iNKT cell-DC crosstalk in tumors.

The spatiotemporal distribution of cytokines orchestrates immune responses in vivo, yet the underlying mechanisms remain to be explored. We showed here that the spatial distribution of interleukin-4 (IL4) in invariant natural killer T (iNKT) cells regulated crosstalk between iNKT cells and dendritic cells (DCs) and controlled iNKT cell-mediated T-helper type 1 (Th1) responses. The persistent polarization of IL4 induced by strong lipid antigens, that is, α-galactosylceramide (αGC), caused IL4 accumulation at the immunological synapse (IS), which promoted the activation of the IL4R-STAT6 (signal transducer and activator of transcription 6) pathway and production of IL12 in DCs, which enhanced interferon-γ (IFNγ) production in iNKT cells. Conversely, the nonpolarized secretion of IL4 induced by Th2 lipid antigens with a short or unsaturated chain was incapable of enhancing this iNKT cell-DC crosstalk and thus shifted the immune response to a Th2-type response. The nonpolarized secretion of IL4 in response to Th2 lipid antigens was caused by the degradation of Cdc42 in iNKT cells. Moreover, reduced Cdc42 expression was observed in tumor-infiltrating iNKT cells, which impaired IL4 polarization and disturbed iNKT cell-DC crosstalk in tumors.

Deep learning for image-based large-flowered chrysanthemum cultivar recognition.

BACKGROUND: Cultivar recognition is a basic work in flower production, research, and commercial application. Chinese large-flowered chrysanthemum (Chrysanthemum × morifolium Ramat.) is miraculous because of its high ornamental value and rich cultural deposits. However, the complicated capitulum structure, various floret types and numerous cultivars hinder chrysanthemum cultivar recognition. Here, we explore how deep learning method can be applied to chrysanthemum cultivar recognition. RESULTS: We propose deep learning models with two networks VGG16 and ResNet50 to recognize large-flowered chrysanthemum. Dataset A comprising 14,000 images for 103 cultivars, and dataset B comprising 197 images from different years were collected. Dataset A was used to train the networks and determine the calibration accuracy (Top-5 rate of above 98%), and dataset B was used to evaluate the model generalization performance (Top-5 rate of above 78%). Moreover, gradient-weighted class activation mapping (Grad-CAM) visualization and feature clustering analysis were used to explore how the deep learning model recognizes chrysanthemum cultivars. CONCLUSION: Deep learning method applied to cultivar recognition is a breakthrough in horticultural science with the advantages of strong recognition performance and high recognition speed. Inflorescence edge areas, disc floret areas, inflorescence colour and inflorescence shape may well be the key factors in model decision-making process, which are also critical in human decision-making.