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It is necessary to manually measure many parameters of eyes when an ophthalmologist diagnoses, which is time consuming, unsanitary, subjective and unrepeatable. Those manually achieved parameters often risk clinical trials in challenges on objectivity, resulting in unreliable clinical conclusions. We designed a two-phase algorithm to automatically measure these parameters instead of manual measurement to facilitate the diagnosis procedure of ptosis, eyelid retraction and other eye pathologies. Firstly, cornea, sclera, and internal and external canthus were identified using a multi-task convolutional neural network (CNN). Then we used the identification results to calculate a series of eye parameters needed in clinic. Totally 9 widely accepted parameters were calculated, including the height of ocular fissure, the longitudinal and transverse diameters of cornea, etc. The experimental results showed that most of parameters had achieved good accuracy, and most errors were less than 2 mm. We found that our approach can improve the measurements accuracy of eyelid, conjunctiva, cornea, sclera, and internal and external canthus, and promote efficiency and efficacy of relative clinical researches.

Thyroid‐associated ophthalmopathy (TAO) is a serious, progressive, vision‐threatening and difficult‐to‐treat organ‐specific autoimmune disease. The course, therapeutic effects and prognosis of moderate to severe TAO vary greatly. High‐dose intravenous glucocorticoid (IVGC) therapy is considered a first‐line treatment for active moderate‐to‐severe TAO, but there is still insufficient evidence regarding the treatment duration. Long‐term IVGC therapy can influence the metabolism of glucose, lipids, and bone. This study was designed to compare changes in metabolic and immunological indexes as well as the magnetic resonance imaging apparent diffusion coefficient (ADC) of the extraocular muscles after 4 and 12 weeks of IVGC therapy. Forty‐eight patients with active moderate‐to‐severe TAO were included in this retrospective cohort study. Metabolism and immunological indexes were measured before and after therapy. The ADC and clinical activity score (CAS) were used to evaluate the efficacy of treatment in these patients. We found that the patients in the 12‐week group had increased fasting plasma glucose (p = 0.004), glycated hemoglobin (p = 0.028), total cholesterol (p

The activities of the ephrin family in breast cancer (BrCa) are complex. Family A receptors (EPHA) and ligands (EFNA) can act as oncogenes or tumor suppressors and are implicated in chemoresistance. Here, we examined the expression pattern and prognostic value of the EPHA/EFNA family in patients with breast cancer, including patients with different subtypes or different chemotherapy cohorts. In the UALCAN database, the mRNA expression of EPHA1, EPHA10, EFNA1, EFNA3, and EFNA4 was significantly higher, whereas that of EPHA2, EPHA4, EPHA5, and EFNA5 was significantly lower in breast cancer tissues than in paracancerous tissues. The transcriptional levels of EPHA/EFNA family members were correlated with intrinsic subclasses of breast cancer. The relationship between EPHA/EFNA and the clinicopathological parameters of BrCa was analyzed using bc-GenExMiner V4.5. EPHA1, EPHA2, EPHA4, EPHA7, EFNA3, EFNA4, and EFNA5 were upregulated in estrogen receptor- (ER-) and progesterone receptor- (PR-) negative tumors, whereas EPHA3, EPHA6, and EFNA1 were upregulated in ER- and PR-positive tumors. EPHA1, EPHA2, EFNA3, and EFNA4 mRNA expression was significantly higher in human epidermal growth factor receptor 2- (HER2-) positive tumors than in HER2-negative tumors. Triple-negative status was positively correlated with EPHA1, EPHA2, EPHA4, EPHA7, EFNA3, EFNA4, and EFNA5 and negatively correlated with EPHA3 and EPHA10 mRNA expression. Genetic alterations of EPHA/EFNA in breast cancer varied from 1.1% to 10% for individual genes, as determined by the cBioPortal database. The Kaplan–Meier plotter indicated that high EphA7 mRNA expression was associated with poor overall survival (OS) and recurrence-free survival (RFS), especially in the HER2 and luminal A subtypes. EFNA4 was predicted to have poor OS and RFS in breast cancers, especially in luminal B, basal-like subtype, and patients treated with adjuvant chemotherapy. High EPHA3 expression was significantly associated with better OS and RFS, especially in the luminal A subtype, but with poor RFS in BrCa patients receiving chemotherapy. Our findings systematically elucidate the expression pattern and prognostic value of the EPHA/EFNA family in BrCa, which might provide potential prognostic factors and novel targets in BrCa patients, including those with different subtypes or treated with chemotherapy.

Many patients with Graves' ophthalmopathy (GO) suffer from dry eye syndrome (DES), and this is one of the most common reasons of eye discomfort in patients with GO. The prevalence of DES in patients with GO is significantly higher than normal subjects. The ocular surface changes involving changes in tears, cornea, conjunctiva and glands occur in GO patients. However, the mechanism of how DES occurs in GO still remains unclear. In this review, the ocular surface changes were illustrated and analyzed the reasons for high prevalence of DES in GO patients.

Objectives: The aim of this study was to compare the efficacy of bioabsorbable steroid-eluting sinus stents versus absorbable Nasopore packs after endoscopic sinus surgery (ESS) for the treatment of chronic rhinosinusitis (CRS). Methods: One hundred eighty-one patients with CRS who underwent ESS were randomly assigned to receive a steroid-eluting sinus stent in one ethmoid sinus cavity, whereas the contralateral control side received a Nasopore pack. Endoscopic evaluations were performed 14, 30, and 90 days after the ESS. Postoperative intervention, polyp formation, adhesions, and middle turbinate (MT) position were assessed as efficacy outcomes. Results: The stents were successfully deployed in all 181 sinuses. Thirty days after the ESS, the stents significantly reduced the need for surgical intervention compared to the Nasopore ( P < .0001). The percentage of cases with polyp formation was significantly lower on the stent sides compared with the Nasopore sides ( P < .0001) at 14, 30, and 90 days after ESS. The percentage of severe adhesion was significantly lower on the stents sides than on the Nasopore sides at postoperative day 90 ( P = .0003), whereas they were not significantly lower at postoperative days 14 and 30. There were no significant differences between the stent sides and the Nasopore sides regarding the frequency of MT lateralization at all end points. No device-related adverse events occurred. Conclusions: Our study demonstrated significant improvement in the early postoperative outcomes by reducing the need for postoperative surgical intervention and polyp formation using steroid-eluting stents when compared with absorbable Nasopore packs. The steroid-eluting sinus stents and the Nasopore packs were each effective in preserving the ethmoid sinus patency and in preventing MT lateralization. A further prospective cohort study with long-term postoperative outcomes is warranted.

Background To investigate the effect of topical application of CpG oligodeoxynucleotide (CpG-ODN) combined with anti-4-1BB antibodies on mouse HCC multiple tumor-bearing models and the degree of improvement of anti-tumor immune response in mice. Materials and Methods We inoculated each BALB/c male mouse subcutaneously with one tumor in the axillae of the four limbs and divided them into four groups. We only selected the tumor-bearing part of the left lower limb for drug treatment. We measured the tumor-bearing volume of mice in each group. Then, we tested the organ coefficients of mice, the concentrations of IL-12 and IFN-γ in peripheral blood, the ratio of spleen Tregs and CD8+T cells, the spleen CTL killing activity, and the survival time of mice. Results We found that the tumor-bearing volume decreased significantly after the combination of CpG-ODN and anti-4-1BB antibody (P 0.05). The concentration of IL-12 and IFN-in serum and the ratio of CD8+T cells in spleen were increased, while the ratio of spleen Tregs was decreased. CTL activity of spleen was increased. The survival time of mice was significantly prolonged (P

Purpose The purpose of this article is to investigate the characteristics of Th1-cell and Th17-cell lineages for very severe Graves orbitopathy (GO) development. Methods Flow cytometry was performed with blood samples from GO and Graves disease (GD) patients and healthy controls, to explore effector T-cell phenotypes. Lipidomics was conducted with serum from very severe GO patients before and after glucocorticoid (GC) therapy. Immunohistochemistry and Western blotting were used to examine orbital-infiltrating Th17 cells or in vitro models of Th17 polarization. Results In GD, Th1 cells predominated in peripheral effector T-cell subsets, whereas in GO, Th17-cell lineage predominated. In moderate-to-severe GO, Th17.1 cells expressed retinoic acid receptor-related orphan receptor-γt (RORγt) independently and produced interleukin-17A (IL-17A), whereas in very severe GO, Th17.1 cells co-expressed RORγt and Tbet and produced interferon-γ (IFN-γ). Increased IFN-γ–producing Th17.1 cells positively correlated with GO activity and were associated with the development of very severe GO. Additionally, GC therapy inhibited both Th1-cell and Th17-cell lineages and modulated a lipid panel consisting of 79 serum metabolites. However, in GC-resistant, very severe GO, IFN-γ–producing Th17.1 cells remained at a high level, correlating with increased serum triglycerides. Further, retro-orbital tissues from GC-resistant, very severe GO were shown to be infiltrated by CXCR3+ Th17 cells expressing Tbet and STAT4 and rich in triglycerides that promoted Th1 phenotype in Th17 cells in vitro. Conclusions Our findings address the importance of Th17.1 cells in GO pathogenesis, possibly promoting our understanding of the association between Th17-cell plasticity and disease severity of GO.

Thyroid-associated ophthalmopathy (TAO) is the most common extrathyroidal manifestation of toxic diffuse goiter (Graves' disease), also known as Graves' ophthalmopathy/orbitopathy. As an organ-specific autoimmune disease, the pathogenesis of TAO is still unclear. In recent years, great progress has been made in revealing the mechanism of TAO. Various biological and immunosuppressive agents have emerged in an endless stream, showing encouraging results. Strengthening the basic research, establishing ideal animal models, deeply understanding the pathogenesis, and developing novel targeted drugs are of great significance to guide the clinical diagnosis and management of TAO and improve the prognosis of patients.

ObjectiveDiet has been reported as the first-line management of polycystic ovary syndrome (PCOS). However, the relationship between diet and fertility in PCOS is still controversial. This meta-analysis aimed to evaluate whether diet could promote reproductive health in women with PCOS while providing evidence-based nutrition advice for clinical practice.MethodsSeven databases, including Cochrane Central Register of Controlled Trials, PubMed, Embase, Web of Science, and some Chinese database, were searched up to January 31, 2021. Randomized controlled trials evaluating the effects of diet in women with PCOS were included. Based on a preregistered protocol (PROSPERO CRD42019140454), the systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Two reviewers made study selection, data extraction and bias assessment independently. Risk ratios and mean difference with 95% confidence intervals were assessed by a random-effects model. Statistical heterogeneity within comparisons was evaluated by Cochran’s Q test and quantified by the I-squared (I2) statistic.ResultsTwenty RCTs with 1113 participants were included. Results showed diet significantly related to improved fertility outcomes (increasing clinical pregnancy, ovulation and menstrual regularity rate; reducing miscarriage rate), reproductive endocrine [increasing sex hormone-binding globulin (SHBG); decreasing Anti-Müllerian Hormone (AMH), free androgen index (FAI), total testosterone (T)] and clinical hyperandrogenism (hirsutism assessed by Ferriman-Gallwey score) in PCOS. Specifically, subgroup analyses indicated low-carbohydrate diets were superior in optimizing reproductive outcomes and calorie restriction was critical in ameliorating hyperandrogenism. Additionally, the positive effects were associated with the treatment duration. The longer the duration, the greater the improvement was.ConclusionOverall, diet is an effective intervention for improving fertility health, thus professional and dynamic dietary advice should be offered to all PCOS patients, based on the changeable circumstances, personal needs and expectations of the individuals.

Background Community-acquired pneumonia (CAP) is a leading infectious cause of hospitalisation and death worldwide. The knowledge about the incidence and aetiology of CAP in China was fragmented. Methods A multicenter study performed at four hospitals in four regions in China and clinical samples from CAP patients were collected and used for pathogen identification from July 2016 to June 2019. Results A total of 1,674 patients were enrolled and the average annual incidence of hospitalized CAP was 18.7 cases per 10,000 people (95% confidence interval 18.5–19.0). The most common viral and bacterial agents found in patients were respiratory syncytial virus (19.2%) and Streptococcus pneumoniae (9.3%). The co-infections percentage was 13.8%. Pathogen distribution displayed variations within age groups, and seasonal and regional differences. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was not detected. Respiratory virus detection was significantly positively correlated with air pollutants, including PM2.5, PM10, NO2 and SO2; and significantly negatively correlated with ambient temperature and O3 content; bacteria detection was opposite. Conclusion The hospitalized CAP incidence in China was higher than previously known. CAP etiology showed differences in age, seasons, regions, and respiratory viruses were detected at a higher rate than bacterial infection overall. Air pollutants and temperature have influence on the detection of pathogens.

Objective: To verify the role of miR-425 in colorectal carcinogenesis. Methods: We conducted sphere formation assay, wound-healing assay, transwell assay, MTT cell proliferation assay, flow cytometric analysis, reverse transcription qPCR, and Western blotting to analyse proliferation and invasion of HCT116 cells transfected with miR-425 mimics, miR-425 inhibitor, miR-425 mimic negative control, and miR-425 inhibitor negative control, respectively. The experimental protocol was approved by the Medical Ethics Committee of the First People’s Hospital in Kashi (approval number: 2018 Kuaishen No. (100)). All experiments were conducted during December 2016 to July 2017 at Xinjiang Dingju Medical Laboratory, China. Results: Our results showed that miR-425 expression in HCT116 cells after transfection was up-regulated, which inhibited sphere formation. Overexpression of miR-425 inhibited proliferation of HTC116 cells and induced their apoptosis, and inhibited HCC116 cell migration and invasion. Conclusion: Overexpression of miR-425 could inhibited sphere formation, the migration and invasion of HCT116 cells through inhibiting proliferation and promoting apoptosis. Keywords: apoptosis; colonic carcinoma; microRNA; proliferation Continuous....

To evaluate the age-related difference in EOMs and its relation to clinical manifestations by computed tomography (CT) measurement of EOMs. The medical records and CT image review of 40 patients (80 orbits) with moderate-to-severe Graves’ orbitopathy were performed. The patients were divided into two age groups, group 1 (≤ 40 years) and group 2 (> 40 years). CT scans of 30 gender- and age-matched normal controls were also obtained. The maximal cross-sectional area (MCA) and its position (pMCA) of each EOM were measured. Group 1 presented with more severe proptosis (p

Background Hepatocellular carcinoma is a common malignant cancer and the second most common cause of cancer-related deaths worldwide. Collagen triple helix repeat containing 1 (CTHRC1) has been increasingly reported to be involved in tumorigenesis and/or tumor progression. However, limited data are available regarding the role of CTHRC1 in hepatocellular carcinoma. Methods Paraffin-embedded specimens from a total of 29 patients with HCC were collected in our study. The expression of CTHRC1 in hepatocellular carcinoma was evaluated using immunohistochemistry and bioinformatics analysis. Furthermore, Spearman analysis was performed to identify factors of correlation between CTHRC1 and clinicopathological features. Survival curves for hepatocellular carcinoma were produced using the Kaplan-Meier method and the log rank test. Results In this study, we confirmed that CTHRC1 is highly expressed in tissues and hepatoma cell lines. The statistical analysis revealed that the levels of CTHRC1 were significantly correlated with cirrhosis (P=0.024), tumor size (P=0.006), vascular invasion (P

Aim Hepatocytes biosynthesize about 80–90% of plasma complement proteins, including complement 3 (C3) and 4 (C4). The purpose of our study is to research the significance of complement in hepatitis B virus related cirrhosis (HBV-cirrhosis), discuss whether C3 and C4 could be served as available markers to assess liver function and prognostic in HBV-cirrhosis. Methods Blood samples were captured from 306 adult patients with HBV-cirrhosis, 23 chronic hepatitis B (CHB) without cirrhosis or liver failure, and 12 healthy adults. Serum C3 and C4 levels were compared in different groups, evaluating the correlation between C3/C4 levels and disease severity in patients with HBV-cirrhosis, analyzing the significance of complement components in infection and mortality of decompensated HBV-cirrhosis. Results The concentrations of C3 and C4 were markedly decreased in HBV-cirrhosis group than those in Chronic Hepatitis B (CHB) and healthy group (p p p

Endometriosis is a chronic estrogen-dependent inflammatory disorder that negatively affects the quality of life in women. The Wenjing decoction (WJD) is a traditional Chinese medicine that has been shown to have a therapeutic effect on endometriosis. Our study systematically explored the mechanism of WJD against endometriosis using a network pharmacology approach. Potentially bioactive compounds of WJD and their possible targets were retrieved from the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform. The protein-protein interaction network and herbs-compounds-genes multinetwork were constructed using Cytoscape for visualization. Subsequently, the signaling pathways of common targets were retrieved from the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, and molecular docking was performed using PyRx software. In total, 48 common targets were screened, such as IL6 and ESR1, which were related to inflammation and the endocrine system. The top five bioactive compounds were quercetin, kaempferol, wogonin, beta-sitosterol, and stigmasterol. KEGG enrichment analysis revealed 65 pathways containing inflammatory- and endocrine-related signaling pathways, such as the “TNF signaling pathway” and the “estrogen signaling pathway.” Taken together, the results of our network pharmacology analysis predicted that certain active ingredients of WJD might treat endometriosis by regulating inflammation and/or endocrine, which provided references for further understanding and exploration of WJD on endometriosis.

Graves’ orbitopathy (GO), also known as thyroid-associated ophthalmopathy, is the most common ocular abnormality of Graves’ disease. It is a disfiguring, invalidating, and potentially blinding orbital disease mediated by an interlocking and complicated immune network. Self-reactive T cells directly against thyroid-stimulating hormone receptor-bearing orbital fibroblasts contribute to autoimmune inflammation and tissue remodeling in GO orbital connective tissues. To date, T helper (Th) 1 (cytotoxic leaning) and Th2 (antibody leaning) cell subsets and an emerging role of Th17 (fibrotic leaning) cells have been implicated in GO pathogenesis. The potential feedback loops between orbital native residential CD34- fibroblasts, CD34+ infiltrating fibrocytes, and effector T cells may affect the T cell subset bias and the skewed pattern of cytokine production in the orbit, thereby determining the outcomes of GO autoimmune reactions. Characterization of the T cell subsets that drive GO and the cytokines they express may significantly advance our understanding of orbital autoimmunity and the development of promising therapeutic strategies against pathological T cells.

BackgroundPrevious studies showed that patients with Graves’ orbitopathy (GO) had concomitant mucosal abnormality within the paranasal sinuses. It remains unknown whether the immunological reactions in sinus mucosa affect the orbit inflammation in GO.MethodsPatients with GO underwent sinus computed tomography (CT) scans for sinus mucosal disease by two independent reviewers using the Lund-MacKay systems. Ethmoid mucosal samples were collected during orbital decompression surgeries for patients with GO and correction surgeries for patients with old orbital fractures as controls. Histological analysis and immunofluorescence were performed in all sinus mucosa tissues. Flow cytometry analysis was used to examine the immunological features of sinus mucosa in both GO and control groups.ResultsImmunohistochemistry showed that the paranasal sinus mucosa of patients with GO grew swelling, with goblet cell and small vessel proliferation, endothelial cell swelling, and inflammatory cell infiltration. The number of T helper (Th)1, Th17, and gamma-delta T cells in nasal sinus mucosa of patients with GO increased significantly compared with those from controls. Further, the proportion of Th1 cells was significantly correlated with clinical activity score. In addition, there was a decreased number of regulatory T cells in patients with GO. The number of Th2 cells showed no significant difference between the two groups. Finally, the proportion of interleukin-22-producing cell subsets in gamma-delta T cells of patients with GO was significantly increased compared with those from controls.ConclusionsOur observations illustrated a potential pathogenic role of mucosal-infiltrating T cells, which may have the possibility to aggravate inflammatory responses in GO.

BackgroundThis study aimed to establish a deep learning system for detecting the active and inactive phases of thyroid-associated ophthalmopathy (TAO) using magnetic resonance imaging (MRI). This system could provide faster, more accurate, and more objective assessments across populations.MethodsA total of 160 MRI images of patients with TAO, who visited the Ophthalmology Clinic of the Ninth People’s Hospital, were retrospectively obtained for this study. Of these, 80% were used for training and validation, and 20% were used for testing. The deep learning system, based on deep convolutional neural network, was established to distinguish patients with active phase from those with inactive phase. The accuracy, precision, sensitivity, specificity, F1 score and area under the receiver operating characteristic curve were analyzed. Besides, visualization method was applied to explain the operation of the networks.ResultsNetwork A inherited from Visual Geometry Group network. The accuracy, specificity and sensitivity were 0.863±0.055, 0.896±0.042 and 0.750±0.136 respectively. Due to the recurring phenomenon of vanishing gradient during the training process of network A, we added parts of Residual Neural Network to build network B. After modification, network B improved the sensitivity (0.821±0.021) while maintaining a good accuracy (0.855±0.018) and a good specificity (0.865±0.021).ConclusionsThe deep convolutional neural network could automatically detect the activity of TAO from MRI images with strong robustness, less subjective judgment, and less measurement error. This system could standardize the diagnostic process and speed up the treatment decision making for TAO.

The springback directly affects the forming accuracy and quality of metal bent-tube, and accurate springback prediction is the key to the springback compensation and control. This paper investigates the springback of mandrel-less rotary draw bending (MLRDB) of circular metal tubes, and an innovative method, springback angle prediction considering the interference of cross-sectional distortion (IoCSD-SAP), is proposed. The digit decomposition condition variational auto-encoder generative adversarial network (D2CVAE-GAN) is developed to augment the data samples. Considering the nonlinear interference of the cross-sectional distortion on springback, auxiliary extended radial basis function (AE-RBF) is proposed. It establishes the mapping relationship between the characteristic parameters and cross-sectional distortion. By extracting the information encode of cross-sectional distortion as the condition input, this model realizes the condition prediction of springback angle. Taking MLRDB of 6060-T6 Al-alloy circular tube as a case study, the proposed method, IoCSD-SAP, is verified. According to the experimental results, the mean absolute percentage error (MAPE) for the springback angle of our proposed method is 4.73%, and three different analytical models are 38.92%, 14.39%, and 14.22%, respectively. It can be seen that our proposed method significantly improves the prediction accuracy of springback angle. For the springback angle prediction of circular metal tube in MLRDB, the data augmentation can effectively reduce the generalization error and improve the prediction accuracy. The nonlinear interference of the cross-sectional distortion on springback should be taken into account to improve the accuracy and robustness of the springback prediction model.

Ethnopharmacological relevance Bu-shen-zhu-yun decoction (BSZYD) is a traditional chinese herbal prescription is widely used in the treatment of infertility. Aim of the study We aimed to elucidate the impact of a traditional herbal prescription BSZYD on polycystic ovary syndrome (PCOS). Materials and methods The candidate active compounds in BSZYD and their putative targets were investigated by bioinformatics analysis. A deydroepiandrosterone (DHEA)-induced PCOS rat model was then constructed using female Sprague-Dawley (SD) rats. Serum hormone levels were measured by enzyme-linked immunosorbent assay (ELISA). Pathological changes in ovarian tissues were analyzed with hematoxylin and eosin (H&E) staining. The expressions of estrogen receptor α (ER α)-mediated PI3K/AKT/mTOR pathway were measured by immunofluorescence and western blotting. Results Bioinformatics analysis showed that the putative targets of active compound candidates in BSZYD were enriched in PI3K/AKT and estrogen signaling pathways related to regulating ovarian ovulation. Animal experiments showed that BSZYD significantly alleviated pathological changes in the ovary, altered hormone levels of serum and reduced apoptosis rate of granulosa cells. In addition, BSZYD treatment notably upregulated the expressions of proteins in ER α-mediated PI3K/AKT/mTOR pathway and downregulated apoptosis-related proteins in PCOS rats. Conclusion BSZYD can restore ovary lesions and ameliorate apoptosis through ER α-mediated PI3K/AKT/mTOR pathway, which might partly contribute to the treatment of PCOS.

OBJECTIVE The surgical treatment of myogenic ptosis accompanying extraocular muscle paralysis is an intractable problem in the field of oculoplastic surgery due to the severe complications such as exposure keratopathy. It is promising to find an appropriate procedure to treat this kind of patients, which is able to ensure the safety and efficacy. METHODS The authors retrospectively reviewed 12 eyes of 6 patients who underwent the under-corrected "double V-Loop" frontalis suspension sling procedure for myogenic ptosis accompanying extraocular muscle paralysis and access the safety and efficacy of this kind of surgery. All the patients underwent corneal fluorescein staining and confocal microscopy before and after the surgery to inspect the corneal condition. The density of central corneal epithelial cells and endothelial cells were observed. RESULTS After the surgery, the eyelids contour was natural, and the symmetry was achieved in these cases. The average palpebral fissures height changed from 2.75 ± 1.41 mm to 4.50 ± 0.35 mm (P = 0.0007) and margin reflex distance 1 changed from -1.25 ± 1.22 mm to +0.50 ± 0.35 mm (P = 0.0002). Out of 12 operated eyes, mild postoperative lagophthalmos was present in 4 cases but without exposure keratopathy during the follow-up, the confocal microscopy showed that there were no significant differences in central corneal superficial epithelial cells (P = 0.93) and endothelial cells (P = 0.90) before and after the surgery. CONCLUSION The under-corrected "double V-Loop" frontalis suspension sling is a proper surgery in myogenic ptosis accompanying extraocular muscle paralysis, which leads to a low occurrence of exposure keratopathy, maintains the integrity of the cornea, and remains the patients' vision function.

Background: Artemisia annua is the most common outdoor aeroallergen throughout Northern China; however, no multicenter study has investigated sublingual immunotherapy (SLIT) as a treatment option for Artemisia annua-induced allergic rhinitis (AR). The aim of this study was to evaluate the efficacy and safety of an innovative SLIT for Artemisia annua-related AR. Methods: This was a randomized, double-blind, placebo-controlled, multicenter, phase 3 clinical trial conducted in China (NCT XXX). A total of 702 Artemisia annua-sensitized eligible patients were randomized in a ratio of 2:1 to receive Artemisia annua-SLIT or placebo. The treatment lasted 32 weeks; including 5-weeks up-dosing phase and 27-weeks maintenance phase. The primary endpoint was the daily combined score of medication and rhinoconjunctivitis symptom (CSMRS), and secondary endpoints were daily total nasal symptom score (dTNSS) and daily rescue medication score (dRMS) during peak pollen period. Safety of treatment was evaluated according to adverse events (AEs) experienced. Results: Mean daily CSMRS was significantly improved during the peak pollen period in the SLIT group compared with the placebo group (1.46 ± 0.47 vs 1.88 ± 0.42, P

Objective To evaluate magnetic resonance imaging parameters, T2 signal intensity ratios (SIRs), and normalized apparent diffusion coefficients (n-ADC) of the extraocular muscles (EOMs) in the identification of different stages of Graves’ ophthalmopathy (GO) and to find out the correlation of T2-SIRs and n-ADC values with disease changes after anti-inflammatory treatment. Methods Altogether, 43 patients (86 orbits) were enrolled and classified into “active” or “inactive” stages by clinical activity score (CAS). Twenty-three (53.5%) patients received anti-inflammatory treatment and underwent a follow-up evaluation. Fifteen age- and gender-matched control participants (30 orbits) were included. T2-SIRs and n-ADC values of EOMs were calculated among GO and healthy controls and were correlated with CAS. Changes in these parameters were also evaluated before and after anti-inflammatory treatment. Results Mean T2-SIRs and n-ADC values were both significantly higher in GO patients than in controls and higher in active GO than in inactive GO. In the inactive stage, n-ADC values of inferior rectus muscles were still higher than those in healthy controls. Both T2-SIRs and n-ADC values decreased after intravenous steroid pulse therapy. The cutoff value of pretreatment n-ADC was 1.780 to detect stages with specificity of 93.7% and sensitivity of 48.3% (P = .035). Conclusion T2-SIRs and n-ADC values are valuable magnetic resonance imaging indicators of the inflammatory activity in GO by detecting involvement of EOMs. They are also ideal tools to monitor the efficacy of anti-inflammatory treatment in patients with active stage GO. n-ADC values, when combined with CAS, can be promising predictive factors in the detection of stages of diseases.

ObjectiveThe effect of diet on insulin resistance (IR) in polycystic ovary syndrome (PCOS) is controversial. Thus, we conducted this systematic review and meta-analysis to evaluate whether diet could reduce IR in women with PCOS while providing optimal and precise nutrition advice for clinical practice.DesignThe search was conducted in 8 databases through June 30, 2019. The systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. A random-effects model was adopted to calculate the overall effects.ResultsA total of 19 trials (1193 participants) were included. The analysis showed that diet was significantly related to improvements in IR and body composition (eg, homeostasis model assessment of insulin resistance, fasting insulin, fasting plasma glucose, body mass index [BMI], weight, and waist circumference) in PCOS patients. The Dietary Approaches to Stop Hypertension diet and calorie-restricted diets might be the optimal choices for reducing IR and improving body composition, respectively, in the PCOS population. Additionally, the effects were associated with the course of treatment. The longer the duration, the greater the improvement was. Compared with metformin, diet was also advantageous for weight loss (including BMI and weight) and had the same effects on insulin regulation.ConclusionOverall, our findings suggest that diet is an effective, acceptable and safe intervention for relieving IR, and professional dietary advice should be offered to all PCOS patients.

Nasopharyngeal carcinoma (NPC) is a malignant tumor with poor prognosis, high morbidity, and mortality. Currently, immunocheckpoint therapy has led to new treatment strategies for almost all cancers, including nasopharyngeal carcinoma. Inducible T-cell aggregation ligand (ICOSL) belongs to the b7-cd28 immunoglobulin superfamily, which is a ligand of ICOS, and also begins to draw attention for its potential usage in cancer treatment. Previous studies from our laboratory have suggested that ICOS expression in tumor-infiltrating lymphocytes is correlated with beneficial outcome, but little is known about the role of ICOSL in NPC. In the current study, ICOSL expression in NPC tumor sections was stained by immunohistochemistry (IHC), and both lymphatic metastasis and distant metastasis showed decreased expression, which was negatively correlated with TNM stage of nasopharyngeal carcinoma. Importantly, high ICOSL expression was significantly associated with overall survival (OS) in patients with NPC (n = 225, p<0.001), and multivariate analysis confirmed that high ICOSL expression was an independent prognostic factor. Fresh nasopharyngeal carcinoma specimens were excised, and the specific expression of cytokines was analyzed by enzyme-linked immunosorbent assay (ELISA). The expression level of ICOSL is positively correlated with interferon-gamma (IFN-γ) concentration in tumor tissues, which is characteristic of T helper 1 (Th1) cells. Knocking down ICOSL by RNAi did not influence the proliferation, migration, and invasion ability of NPC cells. Conclusively, ICOSL expression is associated with increased survival rate in patients with nasopharyngeal carcinoma, which may be a clinical biomarker for prognosis of nasopharyngeal carcinoma.

Polycystic ovarian syndrome (PCOS), the most common endocrine disorder of women in reproductive age, is typical with hyperandrogenism and disturbance of the hypothalamus-pituitary-ovary (HPO) axis, i.e. abnormal expression of hypothalamic gonadotropin-releasing hormone (GnRH) followed by the elevated ratio of serum luteinizing hormone (LH) level to follicle-stimulating hormone (FSH) level. This derangement might have a close relationship with hypothalamic kisspeptin expression that is thought to be a key regulator of GnRH. Crocetin, one of the main components of Saffron clinically used as traditional medicine in gynecology diseases, was evaluated for its therapeutic effects on PCOS induced by prenatally exposure to dihydrotestosterone (DHT) in mice. Herein, we found that DHT-treated mice showed a similar phenotype to human PCOS such as heavier ovary, prolonged diestrus, multiple enlarged follicles with fewer corpus luteum, and higher LH and testosterone levels. Kisspeptin expression was lower in anteroventral periventricular nucleus (AVPV) but higher in arcuate nucleus (ARC). Treatment of crocetin prevented the prolongation of diestrus and reduction in corpora luteum, recover the levels of GnRH, FSH, LH, progesterone (P4), estradiol (E2) and testosterone (T), and increase the kisspeptin level in AVPV but reduce that in ARC. The present study provides in vivo evidence that crocetin improved the PCOS in mice via increasing AVPV-kisspeptin and reducing ARC-kisspeptin expression.

Nasopharyngeal carcinoma (NPC) is a highly malignant tumor, associated with poor patient prognoses, and high rates of morbidity and mortality. Currently, immune checkpoint therapy has brought new treatment strategy for NPC. The inducible T cell co-stimulator (ICOS) belongs to the B7-CD28 immunoglobulin superfamily, which is currently the subject of intense study due to great successes gained in treatment of different malignancies by disrupting their family members. However, the role of ICOS played in NPC remains poorly understood. Immunohistochemistry (IHC) was stained with the ICOS specific antibody and ICOS expression is decreased in patients with either lymphatic or distant metastasis and inversely associated with TNM stage of NPC patients. Importantly, high ICOS expression is significantly correlated with overall survival (OS) of NPC patients (N = 185, p

The use of Chinese medicines (CMs) during pregnancy has long been a major public health concern. Although CMs have been shown to be effective in treating infertility and preventing miscarriage, their use has been restricted, mainly because of limited knowledge of their potential toxicity. Accurate toxicology data are urgently required to assess whether these CMs are safe for maternal health and fetal development. Amniotic fluid (AF) contains carbohydrates, lipids and phospholipids, urea and proteins, all of which aid in the growth of the fetus and reflect the mother's health status as well. The changes in metabolomic patterns of AF are related to pathophysiological occurrences during the course of pregnancy. In this review, we provide a summary of the research performed in recent years on metabolomic AF samples, and use our previous study as an example to explore the feasibility of metabolomics of AF to evaluate the safety of CMs during pregnancy. We believe that metabolomics of AF play a far more important role than traditional morphology methods in the safety evaluation of CMs for pregnancy, with a higher sensitivity and correlation.

Aims Acupuncture is frequently recommended as a complementary therapy for infertility. However, whether acupuncture can prevent early ovarian hyperstimulation syndrome has not been examined and its potential mechanisms are not well understood. Main methods Forty rats were randomized into four groups: Control, Ovarian Stimulation Model, Acupuncture, and Human Chorionic Gonadotropin (HCG). Serum estradiol, progesterone, testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels were measured by enzyme-linked immunosorbent assay. Pituitary ER mRNA and ERβ expression were detected by real-time PCR and western blotting respectively. The pathology of rat ovaries were observed by light microscopy. Key findings We observed significantly lower estradiol levels in the Acupuncture group than in the Model group and increased LH levels in the HCG group than in Model and Acupuncture groups. Testosterone and FSH levels were significantly lower in the Acupuncture group than in the HCG group. Western blotting showed significantly lower pituitary ERβ expression in the Model group than in the Control group and higher expression in the Acupuncture group than in the Model group. Real-time PCR showed lower pituitary ER mRNA expression in the Acupuncture group than in the Model group. Hematoxylin and eosin staining showed a lower proportion of atretic follicles in Acupuncture and HCG groups than in Model and Control groups. Instead, Acupuncture and HCG groups showed growing and mature follicles. Significance Our results demonstrate a relationship between acupuncture and the hypothalamic-pituitary-gonadal axis, and the potential mechanism underlying the preventative effects of acupuncture on the incidence of early ovarian hyperstimulation syndrome.

Background Various distance as well as angle measurements of facial structures are evidence of proper ocular plastic and eyelid disease surgery plans. Surgeons nowadays make decisions based on so called experience, which is non-quantitative, resulting in low dissemination efficiency. Purpose To establish a method for eyelid parameter automatic quantification without mega data labeling and training, facilitating the popularization of eyelid related surgery design. Methods An automatic measurement of eyelid parameters is described. It is composed of obtaining of absolute distance between left inner canthus and right inner canthus by 3D models of human faces, calculation of 22 eyelid parameters based on face landmarks, converting 18 distance-related eyelid parameters’ values which correspond to relative distance to real distance. Results An auto-measurement of 80 normal patients and 60 TAO patients is conducted. By comparison to manual-measurement, we achieved relative errors less than 10% and 13% for regular eyes and diseased eyes. Conclusions Eyelid related characteristics are quantified in an easy, portable and precise way. Based on which, series of approaches in quantitative evaluation, operation selection and extensive dissemination may develop in the fields of eyelid disease and ocular plastics.

Thyroid-associated orbitopathy (TAO) is an inflammatory autoimmune disorder. The most serious complication of TAO is dysthyroid optic neuropathy (DON), which can lead to permanent vision loss because of volume expansion in the orbital apex. Orbital radiation therapy (ORT) is an anti-inflammatory treatment used in the treatment of active TAO. Clinical studies support radiotherapy as having a modest effect on DON, and early radiotherapy may protect against disease progression to DON. Current studies suggest that radiotherapy is generally safe. However, risks still exist in some cases. The possible effects of radiotherapy on TAO, especially complicated with DON, are reviewed. The effects of radiotherapy on DON are not completely known, and evidence from standardized, prospective, and multicenter clinical trials is still lacking.

BACKGROUND The aim of the present study was to establish the normal-range orbital parameters and to explore the relationships between ocular protrusion and various orbital morphological factors. MATERIAL AND METHODS A retrospective, non-comparative case series was conducted from January 2014 to December 2015. We recruited 56 subjects (112 orbits), including 27 males (21 to 87 years of age) and 29 females (22 to 88 years of age) in this study. Nine length measurements, 2 angle measurements, and 2 volume measurements of various aspects of the orbit were obtained using Mimics v18.0 software. The data were collected manually using a 3D measurement technique. Statistical analyses using t tests and Pearson's correlation analyses were performed to evaluate the differences and relationships between the parameters, respectively. RESULTS Ocular protrusion in both sexes was closely related to the following values: orbital soft tissue volume (OSTV) (males: r=0.61, p

Orbital blow out fracture is a common disease in emergency department and a delay or failure in diagnosis can lead to permanent visual changes. This study aims to evaluate the ability of an automatic orbital blowout fractures detection system based on computed tomography (CT) data.Orbital CT scans of adult orbital blowout fractures patients and normal cases were obtained from Shanghai Ninth People's Hospital between January and March 2017. The region of fractures was annotated using 3D Slicer. The Inception V3 convolutional neural networks were constructed utilizing the Python programming language with PyTorch as the framework to extract high dimension features from each slice in a CT scan. These extracted features are processed through a XGBoost model to make the final differentiation of fracture cases and nonfracture ones. Accuracy, receiver operating characteristics, and area under the curve were evaluated.This study used 94 CT scans diagnosed with orbital blowout fractures and 94 healthy control cases. The automatic detection system showed accuracy of 92% in single-image classification and 87% in patient level detection. The area under the receiver operating characteristic curve was 0.9574.Using a deep learning-based automatic detection system of orbital blowout fracture can accurately detect and classify orbital blowout fractures from CT scans. The convolutional neural networks model combined with an accurate annotation system could achieve good performance in a small dataset. Further studies with large and multicenter data are required to refine this technology for possible clinical applications.

Context.— Clinical decision support (CDS) systems could assist less experienced pathologists with certain diagnostic tasks for which subspecialty training or extensive experience is typically needed. The effect of decision support on pathologist performance for such diagnostic tasks has not been examined. Objective.— To examine the impact of a CDS tool for the classification of ovarian carcinoma subtypes by pathology trainees in a pilot observer study using digital pathology. Design.— Histologic review on 90 whole slide images from 75 ovarian cancer patients was conducted by 6 pathology residents using: (1) unaided review of whole slide images, and (2) aided review, where in addition to whole slide images observers used a CDS tool that provided information about the presence of 8 histologic features important for subtype classification that were identified previously by an expert in gynecologic pathology. The reference standard of ovarian subtype consisted of majority consensus from a panel of 3 gynecologic pathology experts. Results.— Aided review improved pairwise concordance with the reference standard for 5 of 6 observers by 3.3% to 17.8% (for 2 observers, increase was statistically significant) and mean interobserver agreement by 9.2% (not statistically significant). Observers benefited the most when the CDS tool prompted them to look for missed histologic features that were definitive for a certain subtype. Observer performance varied widely across cases with unanimous and nonunanimous reference classification, supporting the need for balancing data sets in terms of case difficulty. Conclusions.— Findings showed the potential of CDS systems to close the knowledge gap between pathologists for complex diagnostic tasks.

Broad-spectrum antibiotics are the conservative treatment for tubo-ovarian abscess (TOA) or pelvic abscess, but the failure rate of antibiotic therapy remains higher in patients with a larger abscess. The present study aimed to evaluate the clinical value of early laparoscopic therapy in the management of TOA or pelvic abscess. A total of 100 patients were enrolled and their medical records were retrospectively analyzed after excluding 6 patients with malignant diseases. Based on the treatment they had received, the patients were divided into a conservative treatment group (n=41) and an early laparoscopic treatment group (n=53). In the conservative treatment group, 21 patients (51.2%) finally received laparoscopic exploration (late laparoscopic treatment group), and 20 patients (48.8%) achieved a success of antibiotic therapy (successful antibiotic therapy group). The cut-off value of abscess size for predicting antibiotic treatment failure was determined using receiver operating characteristic curve analysis. Multivariate logistic regression analyses were used to explore the association between the clinical variables and antibiotic therapy failure in conservative treatment group. The durations of elevated temperature >38.0°C and hospitalization were significantly longer in the conservative treatment group than those in the early laparoscopic treatment group (all P

Gut microbiota dysbiosis is closely associated with primary hepatocellular carcinoma (HCC). Recent studies have evaluated the early diagnosis of primary HCC through analysis of gut microbiota dysbiosis. However, the relationship between the degree of dysbiosis and the prognosis of primary HCC remains unclear. Because primary HCC is accompanied by dysbiosis and dysbiosis usually increases the circulatory concentrations of endotoxin and other harmful bacterial substances, which further increases liver damage, we hypothesized that level of dysbiosis associated with primary HCC increases with the stage of cancer progression. To test this hypothesis, we introduced a more integrated index referred to as the degree of dysbiosis (Ddys); and we investigated Ddys of the gut microbiota with the development of primary HCC through high-throughput sequencing of 16S rRNA gene amplicons. Our results showed that compared with healthy individuals, patients with primary HCC showed increased pro-inflammatory bacteria in their fecal microbiota. The Ddys increased significantly in patients with primary HCC compared with that in healthy controls. Moreover, there was a tendency for the Ddys to increase with the development of primary HCC, although no significant difference was detected between different stages of primary HCC. Our findings provide important insights into the use of gut microbiota analysis during the treatment of primary HCC.

Background Postoperative infection is a complication of mandibular distraction osteogenesis (DO) in patients with hemifacial microsomia (HFM). The risk of surgical wound infection in DO is reported to be high due to the long duration of the distraction process. Treatment during the perioperative period is critical in combating infection. Aim This study aimed to evaluate the effectiveness of red-blue irradiation in the prevention of surgical wound infection after mandibular distraction. Methods In our single-centered, randomized clinical study, 118 patients diagnosed with HFM who had undergone DO between April 2016 and April 2018 were included. The patients were randomly divided into two groups: the experimental group received red-blue irradiation treatment and the control group received white-light irradiation. Results None of the infections occurring in this study resulted in serious complications. The postoperative infection rate during the 4 weeks after DO in the experimental group was 1.7%, whereas that in the control group was 13.6% (p = 0.016) (based on a modified NHSN wound infection criterion). The total social cost during the active period for the experimental group was 3386840 RMB, 5.12% higher than for the control group (3221882 RMB). Conclusions Red-blue irradiation is recommended as adjunctive therapy after mandibular distraction osteogeneis in HFM.

Human umbilical cord mesenchymal stem cells (hUMSCs) have been shown to have multiple differentiation potentials. However, a key problem is that only a small number of hUMSCs can migrate to damaged tissue after transplantation. According to “The Theory of Kidney Essence” in Traditional Chinese Medicine, some traditional Chinese medicines used for tonifying the kidneys can be applied in promoting the differentiation and migration of stem cells in vivo. Our previous study demonstrated that icariin (ICA) could up-regulate the pluripotent genes of hUMSCs in vitro and induce cell migration in mice in an acute kidney injury model in vivo. The aim of this study was to investigate the effects of ICA-induced hUMSCs in chronic liver injury (CLI) caused by carbon tetrachloride (CCl4). CLI was induced by intraperitoneal injection of CCl4. ICA-treated hUMSCs were transplanted via intra-venous injection. The animals were followed for survival, biochemistry analysis and pathology. The results show that ICA-treated hUMSCs accelerate the recovery of liver function in mice with CLI. In addition, ICA-treated hUMSCs increase the anti-oxidant activities in liver and prevent the progression to hepatic fibrosis. Moreover, ICA induces the migration of hUMSCs to the injured liver tissue. In conclusion, these data demonstrate that ICA-treated hUMSCs exhibit recovery and protective properties in the mice model of CCl4-induced CLI.

Background Pre-treatment serum albumin (ALB) is a novel index that was identified in recent years and is considered to be closely related to the prognosis of nasopharyngeal carcinoma (NPC). However, the association between ALB and NPC remains controversial. Objective of review To assess the prognostic significance of pre-treatment serum ALB in patients with NPC. Type of review A systematic review and meta-analysis. Search strategy We searched PubMed, the Cochrane Library and the Web of Science for studies published up to August 2018. The keywords used were related to albumin, nasopharyngeal carcinoma and prognosis. Evaluation method We extracted the following data from all included studies: author, publication year, country, cancer centre, time points of randomisation, sample size, mean or median age, gender, TNM stage of NPC, cut-off value of pre-treatment serum albumin, number of high-grade cases and duration of follow-up. Then, we generated the pooled hazard ratios (HR) for overall survival (OS) and distant metastasis-free survival (DMFS) to perform this meta-analysis. Results Ten studies comprising 7339 cases were included. Lower pre-treatment serum ALB levels were significantly associated with worse OS (HR = 1.32, 95% CI 1.17-1.48) and DMFS (HR = 1.40, 95% CI 1.08-1.80). In general, our findings were further verified in the subgroup analyses based on three features, including cancer stage, cut-off value and analysis type. Conclusion A decreased level of pre-treatment serum albumin implies a poor prognosis and can be detected to define the risk stratification of NPC patients.

BACKGROUND Eyelid retraction is the most common and often the first sign of thyroid eye disease (TED). Upper-eyelid retraction causes both functional and cosmetic problems. In order to correct the position of the upper eyelid, surgery is required. Many procedures have demonstrated good outcomes in mild and moderate cases; however, unpredictable results have been obtained in severe cases. Dryden introduced an upper-eyelid-lengthening procedure, which used scleral grafts, but outcomes were unsatisfactory. A new technique is introduced in this study as a reasonable alternative for TED-related severe upper-eyelid retraction correction. MATERIAL AND METHODS An innovative technique for levator lengthening using bovine acellular dermal matrix as a spacer graft is introduced for severe upper-eyelid retraction secondary to TED. Additionally, 2 modifications were introduced: the fibrous cords scattered on the surface of the levator aponeurosis were excised and the orbital fat pad anterior to the aponeurosis was dissected and sutured into the skin closure in a "skin-tarsus-fat-skin" fashion. RESULTS The modified levator-lengthening surgery was performed on 32 eyelids in 26 patients consisting of 21 women and 5 men (mean age, 37.8 years; age range, 19-67 years). After corrective surgery, the average upper margin reflex distance was lowered from 7.7±0.85 mm to 3.3±0.43 mm. Eighteen cases (69%) had perfect results, while 6 cases (23%) had acceptable results. CONCLUSIONS A modified levator-lengthening procedure using bovine acellular dermal matrix as a spacer graft ameliorated both the symptoms and signs of severe upper-eyelid retraction secondary to TED. This procedure is a reasonable alternative for correction of TED-related severe upper-eyelid retraction.

The aim of this study was to compare the surgical outcomes of deep lateral orbital decompression using the rim-sparing technique versus the rim-removal technique in Graves’ orbitopathy (GO). A retrospective cohort study of 75 orbits in 50 patients with GO was performed. Proptosis, best corrected visual acuity (BCVA), intraocular pressure (IOP), upper and lower lid margin to reflex distances (MRD-1 and MRD-2, respectively), diplopia, ocular restriction, and GO quality of life (GO-QOL) questionnaire results were analyzed pre- and postoperatively. The average proptosis reduction ranged from 3.5 mm to 6.7 mm with the rim-sparing technique and from 3.6 mm to 6.7 mm with the rim-removal technique ( P > 0.05). All orbits with dysthyroid optic neuropathy in the rim-sparing group and 87.5% of such orbits in the rim-removal group showed improved BCVA ( P = 0.321). Reductions in IOP, MRD-1, and MRD-2 were observed with both techniques. Patients in the rim-sparing group had greater improvements in GO-QOL appearance score ( P = 0.043). In conclusion, rim-sparing orbital decompression provides efficacious outcomes with greater improvements in patient quality of life than the rim-removal technique. The rim-sparing technique should be considered as a preferable option because it preserves the integrity of the lateral vertical maxillary buttress and bony protection for the orbital contents.

Background Thyroid eye disease (TED) is a debilitating autoimmune orbital disease that is often a result of Graves’ disease. Dysthyroid optic neuropathy (DON) is a rare but sight-threatening manifestation of TED with therapeutic challenges that can potentially lead to visual loss. Case presentation A 74-year-old man experienced active TED with extremely severe redness and swelling of the conjunctiva, loss of visual acuity and exacerbation of disfiguring proptosis. Computed tomography revealed the involvement of extraocular muscles resulting in optic nerve compression. He was in poor general condition and was intolerant to steroids. To achieve the optimal operating conditions for orbital decompression surgery, the patient was initially treated with orbital radiotherapy. The patient responded well, with improvements in clinical activity score and visual acuity. Conclusion This case demonstrates a rare and severe case of DON with therapeutic challenges. To date, no cases has been reported of a patient with such severe and unusual ocular manifestations. Early awareness of the occurrence of optic nerve compression and prompt treatment are important to prevent irreversible outcomes. Orbital radiotherapy should be considered as a useful surgery-delaying alternative for DON, especially in patients who have contraindications to steroids.

A 63-year-old man with altered mental status, septic shock, acute pancreatitis, and meningitis was admitted to the intensive care unit. The patient's anion gap was 24 mmol/L [reference interval (RI), 2–14 mmol/L]. Whole blood lactate was 18 mmol/L (RI, 0.7–2.0 mmol/L), as measured on a Radiometer ABL800 blood gas analyzer. Because the upper analytic measurement range of the ABL800 lactate method is 15 mmol/L, the same sample was repeated on the Roche …

Objective Kangxian Pills, containing Angelicae Sinensis, Chuanxiong Rhizoma, radix paeoniae rubra, and 12 other kinds of Chinese materia medica, have the functions of softening and dispersing blood stasis. It has been used for liver injury and liver fibrosis. The current study was designed to evaluate the anti-hepatic injury activity and the mechanism of Kangxian Pills on a CCl 4 -induced animal model. Methods To induce chronic liver injury, mice were treated with CCl 4 twice a week for four weeks. Kangxian Pills (6 or 12 g/kg) and Compound Biejia Ruangan Tablet (0.901 g/kg) were ig given to mice once daily for four weeks after CCl 4 was withdrawal. The anti-hepatic injury activities and mechanisms of Kangxian Pills were assessed by hepatic histology and by measuring the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin (ALB), and total protein (TP) of serum as well as superoxide dismutase (SOD) and glycogen (Gn) of the liver. Results Kangxian Pills significantly decreased the levels of liver index, ALT, and AST in mice liver injury models in treatment group. Moreover, Kangxian Pills and Compound Biejia Ruangan Tablet inhibited the CCl 4 -induced reduction of SOD and Gn levels in the liver. The histological study showed that Kangxian Pills could reduce cellular swelling and infiltration of inflammatory cells in liver injury. Conclusion Kangxian Pills possess the potent abilities to alleviate chronic liver injury, suggesting that Kangxian Pills exert this effect by enhancing the anti-oxidant ability and metabolism of the liver.

Background Intravenous glucocorticoids (ivGC) have been recommended as a first-line treatment of moderate-to-severe and active thyroid-associated ophthalmopathy (TAO). However, not all patients are responsive to ivGC. The identification of potential factors used to predict their efficacy and the selection of suitable patients have both been lacking. Methods It was a single center retrospective study. Potential factors related to the effects of ivGC were analyzed using logistic regression in 90 consecutive patients with moderate-to-severe and active TAO, who received 4.5 g ivGC therapy. Response was defined as the achievement of at least three points of the overall response. Results Fifty-two (57.8%) patients showed a positive response to ivGC therapy. Significant correlations were observed between the effects of ivGC and pretreatment clinical activity score (CAS), duration of eye symptoms, and restoration of euthyroidism. The two latter factors were both independent. The duration of eye symptoms was negatively correlated with the effects of ivGC, with an odds ratio (OR) of 0.984 (p = 0.012). Restoration of euthyroidism (OR = 3.282, p = 0.039) and pretreatment CAS (OR = 1.653, p

Context T helper (Th)17 cells are correlated with many human autoimmune disorders, including Graves disease, and may play key roles in the pathogenesis of Graves orbitopathy (GO). Objective To study the phenotype of Th17 cells in patients with GO and healthy subjects, investigate the fibrosis and adipogenesis in orbital fibroblasts (OFs) modulated by interleukin (IL)-17A, and determine the interaction between Th17 cells and OFs. Design/Setting/Participants Blood samples and orbital tissues from GO patients and healthy controls were collected. Main Outcome Measures We conducted multicolor flow cytometry, immunohistochemical and immunofluorescent stainings, Western blotting, a PathScan intracellular signaling assay, Luminex and enzyme-linked immunosorbent assays, and protein mass spectrum. Results Interferon-γ– and IL-22–expressing Th17 cells are increased in GO patients, which are positively related to clinical activity score. Costimulatory molecules are highly expressed in GO orbits and most GO OFs are CD90+. IL-17A promotes TGF-β–induced fibrosis in CD90+ OFs but impedes 15-deoxy-Δ12,14-prostaglandin J2–induced adipogenesis in CD90− OFs. Th17 cells promote proinflammatory cytokine secretion in both CD90+ and CD90− OFs. Meanwhile, both CD90+ and CD90− OFs contribute to Th17 cell differentiation through prostaglandin E2 production, which can be attenuated by indomethacin. Furthermore, Th17 cells upregulate costimulatory molecule expression on OFs. Conclusion Our findings unravel the pathogenicity of IL-17A in the initiation and progression of GO. In-depth interpretation of the molecular basis of OFs delineated by CD90 and Th17–OF interaction will help to afford a novel approach to better therapeutic strategies for GO.

Between January 2006 and December 2009, dural ossification (DO) was found intraoperatively in 26 of 98 patients with thoracic spinal stenosis due to ossification of the ligamentum flavum (OLF). MRI showed single-level (n = 2), two-level (n = 8) and multilevel (n = 16) areas of low signal intensity in the ligamentum flavum of the thoracic spine. Of the 68 ossified segments in the study population, 11 (16.2%) were located in the upper thoracic spine (T1-T4), nine (13.2%) were located in the midthoracic spine (T5-T8), and 48 (70.6%) were located in the lower thoracic spine (T9-L1). All patients underwent en bloc resection of the areas affected by OLF and DO. All patients underwent posterior decompression; we did not use instrumented fusion to restore the stability of the involved segments after decompression for any patient. The dural defect was not repaired. The neurological status had improved at follow up (22-66 months; mean, 46.7 months) from a preoperative mean Japanese Orthopaedic Association score of 5.46 ± 1.73 points to 8.92 ± 1.38 points at the last follow up (t = 13.87, p < 0.05). The mean values for preoperative and postoperative kyphosis of the involved vertebrae were 6.6 ± 1.5° and 8.2 ± 1.4°, respectively; the mean increase in kyphosis was only 1.7 ± 1.4°. Thus, the surgical techniques discussed in this paper for treatment of OLF associated with DO in the thoracic spine, are effective.

Purpose This present study aims to investigate the phenotype of IL-17A-producing T cells in thyroid-associated ophthalmopathy (TAO) and the role of IL-17A on RANTES and IL-16 expression in orbital fibroblasts (OFs) from TAO patients. Methods Blood samples were obtained from TAO patients and healthy controls and were subjected to ELISA and flow cytometry analysis. Primary human OFs cultured from surgical wastes were stimulated with IL-17A in the presence or absence of CD40L and were examined by qRT-PCR, ELISA, Western blotting, and apoptosis assays. Results We reported upregulated IL-17A, IFN-γ, RANTES, and IL-16 serum levels and increased frequency of IL-17A- and IFN-γ-producing T cells in peripheral blood mononuclear cells from patients with TAO compared with healthy controls. In addition, TAO orbital tissues were rich in T lymphocytes, expressing more IL-17A, IFN-γ, RANTES, and IL-16. Moreover, IL-17A could enhance the expression of RANTES, but not IL-16, in cultured primary OFs in cooperation with CD40L. We further validated that MAPK signaling was largely responsible for RANTES production in IL-17A-treated OFs. Finally, we demonstrated that IL-17A could not promote apparent apoptosis in OFs from TAO patients and healthy controls. Conclusions Our results indicate the potent effect of IL-17A-induced RANTES expression on OFs and elaborate a possible mechanism in understanding Th17 cells in the pathology of TAO and its potential as a target to immunotherapy of TAO and other autoimmune disorders.