Acute phase clinical manifestations of patients with Vogt-Koyanagi-Harada disease in Southern China.

BACKGROUNDS: To characterize the acute phase clinical manifestations and visual outcomes of the patients with Vogt-Koyanagi Harada (VKH) disease in southern China. METHODS: In total, 186 patients with acute-onset VKH disease were recruited. The demographic data, clinical signs, ophthalmic examinations, and visual outcomes were analyzed. RESULTS: Among the 186 VKH patients, 3 were diagnosed as complete VKH, 125 as incomplete VKH, and 58 as probable VKH. All patients visited the hospital within 3 months of onset and complained of decreased vision. For the extraocular manifestations, 121 patients (65%) referred neurological symptoms. Anterior chamber activity was negative in most eyes within an onset of 7 days, which increased slightly with onset beyond 1 week. Exudative retinal detachment (366 eyes, 98%) and optic disc hyperaemia (314 eyes, 84%) were commonly observed at presentation. A typical ancillary examination helped with the diagnosis of VKH. Systemic corticosteroid therapy was prescribed. The logMAR best-corrected visual acuity improved significantly from 0.74 ± 0.54 at baseline to 0.12 ± 0.24 at the 1-year follow-up visit. The recurrence rate was 18% in the follow-up visits. Erythrocyte sedimentation rate and C-reactive protein were significantly correlated to VKH recurrences. CONCLUSION: Posterior uveitis, followed by mild anterior uveitis, is the typical initial manifestation in the acute phase of Chinese VKH patients. Visual outcome improvement is promising in most patients receiving systemic corticosteroid therapy in the acute phase. Detection of the clinical features at the initial onset of VKH could facilitate early treatment and better vision improvement.

Baicalein ameliorates Alzheimer's disease via orchestration of CX3CR1/NF-κB pathway in a triple transgenic mouse model.

Alzheimer's disease (AD) is a common chronic neurodegenerative disease. Some studies have suggested that dysregulation of microglia activation and the resulting neuroinflammation play an important role in the development of AD pathology. Activated microglia have both M1 and M2 phenotypes and inhibition of M1 phenotype while stimulating M2 phenotype has been considered as a potential treatment for neuroinflammation-related diseases. Baicalein is a class of flavonoids with anti-inflammatory, antioxidant and other biological activities, but its role in AD and the regulation of microglia are limited. The purpose of this study was to investigate the effect of baicalein on the activation of microglia in AD model mice and the related molecular mechanism. Our results showed that baicalein significantly improved the learning and memory ability and AD-related pathology of 3 × Tg-AD mice, inhibited the level of pro-inflammatory factors TNF-α, IL-1ß and IL-6, promoted the production of anti-inflammatory factors IL-4 and IL-10, and regulated the microglia phenotype through CX3CR1/NF-κB signaling pathway. In conclusion, baicalein can regulate the phenotypic transformation of activated microglia and reduce neuroinflammation through CX3CR1/NF-κB pathway, thereby improving the learning and memory ability of 3 × Tg-AD mice.

Identification and diagnosis of meniscus tear by magnetic resonance imaging using a deep learning model.

Objective: Meniscus tear is a common problem in sports trauma, and its imaging diagnosis mainly relies on MRI. To improve the diagnostic accuracy and efficiency, a deep learning model was employed in this study and the identification efficiency was evaluated. Methods: Standard knee MRI images from 924 individual patients were used to complete the training, validation and testing processes. Mask regional convolutional neural network (R-CNN) was used to build the deep learning network structure, and ResNet50 was adopted to develop the backbone network. The deep learning model was trained and validated with a dataset containing 504 and 220 patients, respectively. Internal testing was performed based on a dataset of 200 patients, and 180 patients from 8 hospitals were regarded as an external dataset for model validation. Additionally, 40 patients who were diagnosed by the arthroscopic surgery were enrolled as the final test dataset. Results: After training and validation, the deep learning model effectively recognized healthy and injured menisci. Average precision for the three types of menisci (healthy, torn and degenerated menisci) ranged from 68% to 80%. Diagnostic accuracy for healthy, torn and degenerated menisci was 87.50%, 86.96%, and 84.78%, respectively. Validation results from external dataset demonstrated that the accuracy of diagnosing torn and intact meniscus tear through 3.0T MRI images was higher than 80%, while the accuracy verified by arthroscopic surgery was 87.50%. Conclusion: Mask R-CNN effectively identified and diagnosed meniscal injuries, especially for tears that occurred in different parts of the meniscus. The recognition ability was admirable, and the diagnostic accuracy could be further improved with increased training sample size. Therefore, this deep learning model showed great potential in diagnosing meniscus injuries. Translational potential of this article: Deep learning model exerted unique effect in terms of reducing doctors' workload and improving diagnostic accuracy. Injured and healthy menisci could be more accurately identified and classified based on training and learning datasets. This model could also distinguish torn from degenerated menisci, making it an effective tool for MRI-assisted diagnosis of meniscus injuries in clinical practice.

The diagnostic value of 3.0T MRI in cesarean scar pregnancy.

OBJECTIVE: The purpose was to evaluate the diagnostic value of 3.0T MRI in cesarean scar pregnancy (CSP). METHODS: 56 patients with suspected CSP treated in our hospital from August 2018 to July 2020 were recruited as the study cohort and diagnosed using ultrasound and 3.0T MRI. With the pathological examination results as the gold standard and the ultrasound examination results as a comparison, the diagnostic value of 3.0T MRI was evaluated according to the diagnostic accuracy, sensitivity, specificity, and positive and negative misdiagnosis rates, etc. Results: The pathological examination showed that 33 patients were positive for CSP but the other 23 were negative. The accuracy, sensitivity, and specificity of 3.0T MRI in the CSP diagnoses were significantly higher than the accuracy, sensitivity, and specificity of the ultrasound diagnoses (P<0.05), and the positive and negative misdiagnosis rates were significantly lower than the misdiagnosis rates of the ultrasound diagnosis (P<0.05). Moreover, the images from two patients showed that 3.0T MRI can provide clear images of the patients' lesion locations. CONCLUSION: Compared with ultrasound diagnoses, 3.0TMRI has significant advantages in diagnosing CSP and has a high clinical value.

First Report of Alfalfa Root Rot Caused by Plectosphaerella cucumerina in Inner Mongolia Autonomous Region of China.

Alfalfa (Medicago sativa L.) is an important forage crop with high nutrition for animal feed. In May 2016, a disease showing brown root rot was observed on alfalfa collected from several farms in Tongliao City (44°17' N; 121°29' E), Inner Mongolia Autonomous Region of China. The incidence of brown root rot was approximately 50 to 70% in the 2-year-old alfalfa field. Infected alfalfa exhibited varying degrees of decay in the tap root. Symptomatic roots were cut into 0.5-cm pieces, surface disinfected with 70% ethanol for 5 s and 0.1% HgCl2 for 35 s, then rinsed with sterilize distilled water three times, and placed onto potato dextrose agar (PDA) at 26°C in the dark. After 5 days, hyphal tips of the growing colonies were transferred onto PDA plates for purification. Forty-four isolates belonging to five fungal species were obtained from 20 diseased root samples. Six of the isolates resembled the genus Plectosphaerella. Colonies of these isolates were white to cream in color with sparse aerial mycelium, and then gradually became salmon pink with slimy or moist mycelium. The hyphae were transparent and branched. Colonies produced numerous hyphal coils with conidiophores. Conidiogenous cells and conidia were both hyaline, solitary, and smooth. Conidia were 4 to 8.5 ×1.2 to 4.8 µm (n= 100), 0 to 1 septum, elliptical and ovoid, and aggregating to form a head (Palm et al. 1995). According to these morphological characteristics, the fungus was identified as P. cucumerina (Lindf.) (Carlucci et al. 2012). To confirm the identification, the genomic DNA of two representative isolates was extracted and their internal transcribed spacer (ITS) region was amplified and sequenced with the primer pair ITS1/ITS4 (White et al. 1990). The ITS sequences of the two isolates were deposited in GenBank (acc. nos. MN915126 and MN915127). The two ITS sequences showed 99 to 100% identical to known P. cucumerina strains CBS 131739 (acc. no. KY662258.1) (Su et al. 2017) and MP313 (acc. no. KC756835.1) from alfalfa in China (Wen et al. 2015). To test for pathogenicity, a set of 15 alfalfa seedlings (cv. Aohan) were root-dipped in the conidial suspension of one of the isolates (1×105 conidia /ml) prepared from 7-day-old cultures on PDA. Inoculated seedlings were transplanted in three pots (10×15 cm) with sterilized nursery soil. Another set of five alfalfa seedlings inoculated with sterile water only served as the controls. Treated alfalfa seedlings were maintained in a greenhouse at 25°C to 28°C under a 12-h photoperiod. After 25 days, the roots of all inoculated plants showed brown lesions. P. cucumerina was reisolated from symptomatic tissue. No symptoms were observed on the control plants. P. cucumerina was previously reported on alfalfa in the fields of Huanxi Country (36°20' N; 107°21'), Gansu Province, China (Wen et al. 2015). To our knowledge, this is the first report of P. cucumerina causing root rot of alfalfa in Inner Mongolia Autonomous Region, China. This disease may cause serious economic losses in the region. It is needed to develop effective management strategies for control of this disease.

Acupoint injection in improving pain and joint function of knee osteoarthritis patients: A protocol for systematic review and meta-analysis.

BACKGROUND: Knee osteoarthritis is a common chronic progressive disease, which seriously affects the quality of life of the middle-aged and elderly, and even leads to disability. More and more evidence shows that acupoint injection is beneficial to the clinical treatment of knee osteoarthritis, but there are differences in the efficacy of different acupoints and injection drugs, and there is no systematic review to assess this therapy at present. The purpose of this study is to systematically evaluate the efficacy and safety of acupoint injection in improving pain and joint function in patients with knee osteoathrosis. METHODS: According to the retrieval strategy, we will search from CNKI, Wanfang, VIP, Chinese Biomedical Science, PubMed, Embase, Web of Science and the Cochrane Library for randomized controlled trials of acupoint injection in the treatment of knee osteoarthritis from the establishment of the database to February 2021. The study will be screened according to the inclusion and exclusion criteria, and the Cochrane risk bias assessment tool will be used to evaluate the quality of the study. Revman 5.4 software is used for meta-analysis. RESULTS: This study will evaluate the efficacy of acupoint injection in the treatment of knee osteoarthritis by evaluating the total effective rate, the degree of pain relief, joint function score, adverse reactions, and so on. CONCLUSION: This study will provide reliable evidence-based basis for the clinical application of acupoint injection in the treatment of knee osteoarthritis. ETHICS AND DISSEMINATION: Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval will not be required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences.OSF Registration number-doi: 10.17605/OSF.IO/M5FTK.

Curcumin inhibits APOE4-induced injury by activating peroxisome proliferator-activated receptor-γ (PPARγ) in SH-SY5Y cells.

OBJECTIVES: The human apolipoprotein E4 (APOE4) is associated with various brain injuries and neurodegenerative changes. Curcumin is an active ingredient isolated from the root of turmeric and is believed to have therapeutic effects on neurodegenerative diseases. The aim of this study was to investigate the effects of curcumin on APOE4-induced neurological damage and explore its molecular mechanisms. MATERIALS AND METHODS: SH-SY5Y cells were pretreated with curcumin for 24 hr and transfected with human APOE4 gene using Lipofectamine 2000. Then, the effect of curcumin on the transfected cells was detected by ELISA, immunofluorescence staining and Western blot. RESULTS: The production or expression of proinflammatory cytokines and proteins, including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), nitric oxide (NO), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) was significantly increased in SH-SY5Y cells transfected with APOE4, and curcumin inhibited APOE4-induced cellular inflammatory damage. Western blot analysis showed that, after transfection with APOE4, the expression of total nuclear factor kappa B (NF-κB) p65 and p-NF-κB p65 in the nucleus was increased, and curcumin inhibited the nuclear translocation of p65. The overexpression of APOE4 inhibited the expression of peroxisome proliferator-activated receptor-γ (PPARγ), whereas curcumin reversed and increased the expression of PPARγ protein. Down-regulating PPAR-γ with the inhibitor GW9662 and the shPPARγ gene confirmed that the NF-κB signaling pathway was inhibited by PPARγ. CONCLUSION: This study suggests that APOE4 overexpression can induce cellular inflammatory damage, and pretreatment of curcumin could exert an anti-inflammatory effect by upregulating the expression of PPARγ to inhibit the activation of NF-κB signaling pathway.

Quercetin­3­O­α­L­rhamnopyranoside derived from the leaves of Lindera aggregata (Sims) Kosterm. evokes the autophagy­induced nuclear factor erythroid 2­related factor 2 antioxidant pathway in human umbilical vein endothelial cells.

Quercetin­3­O­α­L­rhamnopyranoside (QI) is derived from the leaves of Lindera aggregata (Sims) Kosterm. And exhibits multiple biological activities, including an antioxidant activity. However, the detailed molecular mechanism of its antioxidant activity remains unknown. The aim of the present study was to investigate the antioxidant activity of QI and the underlying molecular mechanism in human umbilical vein endothelial cells (HUVECs). An oxidative stress model was established in HUVECs using H2O2, and cells were then treated with different concentrations of QI. The results revealed that the exposure of HUVECs to QI protected these cells from H2O2­induced damage. QI treatment also increased the activities of the antioxidant enzymes superoxide dismutase (SOD) and glutathione (GSH) in the cell culture medium. In addition, QI inhibited H2O2­induced apoptosis by decreasing the expression levels of cleaved Caspase­9 and poly(ADP­ribose) polymerase. QI also inhibited the production of DNA fragments and reactive oxygen species induced by H2O2. Furthermore, QI decreased the oxidative stress by promoting the nuclear transfer of nuclear factor erythroid 2­related factor 2 (Nrf2) and heme oxygenase­1 by activating autophagy, and inhibited the competition of Bach1 from Nrf2. Finally, QI significantly improved the activities of T­SOD and GSH, and decreased the content of malondialdehyde in the serum and heart tissue of aging rats. These data support the use of QI as a health supplement to alleviate oxidative stress or further development of this compound as an antioxidant drug.

Cigarette smoke extract induces the epithelial-to-mesenchymal transition via the PLTP/TGF-ß1/Smad2 pathway in RLE-6TN cells.

Aim: The role of phospholipid transfer protein (PLTP) in the pathogenesis of the cigarette smoke extract (CSE)-induced epithelial-to-mesenchymal transition (EMT) has not been well described. In this study we investigated the effect of PLTP on the CSE-induced EMT of rat alveolar epithelial cells (RLE-6TN). Methods: The rats were exposed to air and cigarette smoke (CS) for 3 d and then the lungs were sectioned and examined using immunohistochemistry techniques. RLE-6TN cells were treated with different concentrations of CSE. PLTP siRNA was transfected into cells or SB431542 - an inhibitor of the transforming growth factor-ß1 (TGF-ß1) type I receptor - was administered prior to CSE exposure. The expression of EMT markers and PLTP was detected by qRT-PCR. The levels of PLTP, TGF-ß1, p-Smad2, Smad2, and EMT proteins were analyzed by western blotting. Results: Lung injury and EMT were accompanied by up-regulation of PLTP and TGF-ß1 in the CS-exposed rat model. EMT was induced by CSE in vitro, and the expression of PLTP, TGF-ß1, and p-Smad2 was significantly increased after exposure to CSE (P < 0.05). Moreover, knockdown of PLTP and blocking of the TGF-ß1/Smad2 pathway restrained the CSE-induced activation of the TGF-ß1/Smad2 pathway and partly inhibited EMT by reversing E-cadherin expression and retarding the induction of N-cadherin and vimentin. In contrast, SB431542 had no effect on the expression of PLTP, while it ameliorated CSE-induced EMT. Conclusion: PLTP promotes the CSE-induced EMT process, in which the TGF-ß1/Smad2 pathway is activated.

Effect of Phospholipid Transfer Protein on Cigarette Smoke Extract-Induced IL-8 Production in Human Pulmonary Epithelial Cells.

To investigate the effect of phospholipid transfer protein (PLTP) on the cigarette smoke extract (CSE)-induced production of interleukin-8 (IL-8) in human pulmonary epithelial cells, male Wistar rats were exposed to air and cigarette smoke (n = 10/exposure) for 6 h/day on three consecutive days. Their lungs were sectioned and bronchoalveolar lavage fluid (BALF) examined. The expression of PLTP and IL-8 in the lung was detected immunohistochemically. Lung injury was accompanied by the upregulation of PLTP and IL-8 in the CSE-exposed rat model, and the number of white blood cells in the BALF was significantly increased compared with those of the controls. Both neutrophils and macrophages were clearly increased. Human alveolar epithelial cells (A549) and human bronchial epithelial cells (HBECs) were treated with different concentrations of CSE for various times. The cells were also transfected with small interfering RNA directed against PLTP, and U0126, an inhibitor of the ERK1/2 pathway, was administered before CSE exposure. The expression of PLTP and IL-8 mRNAs and PLTP, IL-8, total ERK, and phosphorylated ERK proteins was analyzed. The expression of IL-8 and phosphorylated ERK was significantly increased in A549 cells and HBECs after CSE stimulation, and CSE upregulated the expression of PLTP in A549 cells. In contrast, CSE inhibited the expression of PLTP in HBECs. The CSE-induced expression of IL-8 and p-ERK was significantly increased by the knockdown of PLTP. Therefore, PLTP may regulate CSE-induced IL-8 expression via the ERK1/2 signaling pathway in human pulmonary epithelial cells.

[Study on the clinical use of alpha-fetoprotein (AFP) colloidal gold diagnostic strip].

OBJECTIVE: To test the sensitivity and specificity of alpha-fetoprotein (AFP) colloidal gold diagnostic strip as compared with RIA-AFP diagnostic kit. METHODS: Double blind method was used to test sera from 426 healthy people and 1567 patients selected in two general hospitals and a cancer hospital. Each serum was measured by RIA-AFP and AFP colloidal gold diagnostic strip on the same day. RIA-AFP diagnostic results was identified as true positive or negative. RESULTS: Among 426 healthy people, all the RIA-AFP test showed negative result (serum AFP concentration less than 25 IU/ml), but the AFP colloidal gold diagnostic strip had 1.88% false positive. When comparing the result from 1567 patients measured by RIA-AFP, the sensitivity and specificity of AFP colloidal gold diagnostic strip were 99.3%, and 97.2%, respectively. The crude correspondence rate between the two diagnostic regents was 97.6%. CONCLUSION: AFP colloidal gold diagnostic strip showed very good result and could be used as a screening diagnostic kit in clinic and hospital settings.