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Mechanisms leading to age-related reductions in bone formation and subsequent osteoporosis are still incompletely understood. We recently demonstrated that kynurenine (KYN), a tryptophan metabolite, accumulates in serum of aged mice and induces bone loss. Here, we report on novel mechanisms underlying KYN's detrimental effect on bone aging.We show that KYN is increased with aging in murine bone marrow mesenchymal stem cells (BMSCs). KYN reduces bone formation via modulating levels of CXCL12 and its receptors as well as histone deacetylase 3 (Hdac3). BMSCs responded to KYN by significantly decreasing mRNA expression levels of CXCL12 and its cognate receptors, CXCR4 and ACKR3, as well as downregulating osteogenic gene RUNX2 expression, resulting in a significant inhibition in BMSCs osteogenic differentiation. KYN's effects on these targets occur by increasing regulatory miRNAs that target osteogenesis, specifically miR29b-1-5p.Thus, KYN significantly upregulated the anti-osteogenic miRNA miR29b-1-5p in BMSCs, mimicking the up-regulation of miR-29b-1-5p in human and murine BMSCs with age. Direct inhibition of miR29b-1-5p by antagomirs rescued CXCL12 protein levels downregulated by KYN, while a miR29b-1-5p mimic further decreased CXCL12 levels. KYN also significantly downregulated mRNA levels of Hdac3, a target of miR-29b-1-5p, as well as its cofactor NCoR1. KYN is a ligand for the aryl hydrocarbon receptor (AhR). We hypothesized that AhR mediates KYN's effects in BMSCs. Indeed, AhR inhibitors (CH-223191 and 3′,4′-dimethoxyflavone [DMF]) partially rescued secreted CXCL12 protein levels in BMSCs treated with KYN. Importantly, we found that treatment with CXCL12, or transfection with an miR29b-1-5p antagomir, downregulated the AhR mRNA level, while transfection with miR29b-1-5p mimic significantly upregulated its level. Further, CXCL12 treatment downregulated IDO, an enzyme responsible for generating KYN. Our findings reveal novel molecular pathways involved in KYN's age-associated effects in the bone microenvironment that may be useful translational targets for treating osteoporosis.

PurposeThe neural bases in acute tinnitus remains largely undetected. The objective of this study was to identify the alteration of the brain network involved in patients with acute tinnitus and hearing loss.MethodsAcute tinnitus patients (n = 24) with hearing loss and age-, sex-, education-matched healthy controls (n = 21) participated in the current study and underwent resting-state functional magnetic resonance imaging (fMRI) scanning. Regional homogeneity and amplitude of low-frequency fluctuation were used to investigate the local spontaneous neural activity and functional connectivity (FC), and Granger causality analysis (GCA) was used to analyze the undirected and directed connectivity of brain regions.ResultsCompared with healthy subjects, acute tinnitus patients had a general reduction in FC between auditory and non-auditory brain regions. Based on FC analysis, the superior temporal gyrus (STG) revealed reduced undirected connectivity with non-auditory brain regions including the amygdala (AMYG), nucleus accumbens (NAc), the cerebellum, and postcentral gyrus (PoCG). Using the GCA algorithm, increased effective connectivity from the right AMYG to the right STG, and reduced connectivity from the right PoCG to the left NAc was observed in acute tinnitus patients with hearing loss. The pure-tone threshold was positively correlated with FC between the AMYG and STG, and negatively correlated with FC between the left NAc and the right PoCG. In addition, a negative association between the GCA value from the right PoCG to the left NAc and the THI scores was observed.ConclusionAcute tinnitus patients have aberrant FC strength and causal connectivity in both the auditory and non-auditory cortex, especially in the STG, AMYG, and NAc. The current findings will provide a new perspective for understanding the neuropathophysiological mechanism in acute tinnitus.

In insects, imaginal disk growth factors (IDGFs), an important component of the glycoside hydrolase 18 (GH18) family of chitinases, have been reported to be associated with the maintenance of the cuticle and molting. However, there is little knowledge of their function. In this study, imaginal disk growth factor 6 (Idgf6), which is an Idgf, was first identified and cloned from the guava fruit fly Bactrocera correcta (Bezzi) (Diptera: Tephritidae), one of the most serious pest insects in South China and surrounding Southeast Asian countries. This gene encodes IDGF6 protein with a conserved domain similar to ChiA chitinases, the glycoside hydrolase 18 (GH18) family of chitinases, according to NCBI BLAST. Phylogenetic analysis indicated that all Idgf6s were highly conserved among similar species. Subsequent temporal expression profiling revealed that Idgf6 was highly expressed in both the late-pupal and mid-adult stages, suggesting that this gene plays a predominant role in pupal and adult development. Furthermore, RNA interference experiments against Idgf6 in B. correcta, which led to the specific decrease in Idgf6 expression, resulted in larval death as well as adult wing malformation. The direct effects of Idgf6 silencing on B. correcta indicated its important role in development, and Idgf6 might be further exploited as a novel insecticide target in the context of pest management.

Pleural effusions are associated with a variety of disease states, rendering the differential diagnosis challenging. Spondylodiscitis is an uncommon disease, and its prompt diagnosis can reduce morbidity and mortality. However, an atypical manifestation of the disease, such as pleural effusion, can result in delayed diagnosis. A 76-year-old woman presented with back pain and right pleural effusion. Magnetic resonance imaging revealed paravertebral soft tissue infiltration, with enhancement of bone marrow and intervertebral disk at the T8 and T9 levels, suggesting spondylodiscitis. In patients with exudative pleural effusion, spondylodiscitis may be the cause, so careful analysis of imaging is necessary.

Adenocarcinoma is the most common type of non-small cell lung cancer. Some causative genomic alterations in epidermal growth factor receptor (EGFR), including deletions in exon 19 (E19 dels) and a point mutation in E21, are known to have favourable prognoses due to sensitivity to tyrosine kinase inhibitors; however, the prognoses of other uncommon mutations are unclear. This study analysed the clinical significance of EGFR mutation types in lung adenocarcinoma. We retrospectively reviewed 1,020 subjects (mean age: 66.8 years, female: 41.7%) who were diagnosed with advanced lung adenocarcinoma, had EGFR mutation data, and did not undergo surgery from five medical institutes between 2010 and 2016. Subjects were classified according to EGFR mutation status, particularly for exon-specific mutations. EGFR positivity was defined as the presence of mutation and EGFR negativity was defined as wild-type EGFR. EGFR positivity was 38.0%, with the incidence of mutations in E18, E19, E20, and E21 was 3.6%, 51.0%, 3.4%, and 42.0%, respectively. The EGFR positive group survived significantly longer than the negative group (p

Abstract Background Predatory stress as a psychological stressor can elicit the activation of the hypothalamic–pituitary–adrenal (HPA) axis, which is involved in the dialogue of the neuroimmunoendocrine network. The brain has been proven to regulate the activity of the HPA axis by way of lateralization. In the present study, we probed the pivotal elements of the HPA circuitry including CRH, GR and a multifunctional cytokine in behavior-lateralized mice to determine their changes when the animals were subjected to predator exposure. Methods Behavior-lateralized mice were classified into left-pawed and right-pawed mice through a paw-preference test. Thereafter, mice in the acute stress group received a single 60-min cat exposure, and mice in the chronic group received daily 60-min cat exposure for 14 consecutive days. The plasma CS and TNF-α were determined by ELISA, the hypothalamic CRH mRNA and hippocampal GR mRNA were detected by real-time PCR, and the hippocampal GR protein was detected by western blot analysis. Results The results revealed that the levels of plasma CS were significantly elevated after chronic predatory exposure in both right-pawed and left-pawed mice; the right-pawed mice exhibited a higher plasma CS level than the left-pawed mice. Similarly, the acute or chronic cat exposure could induce the release of plasma TNF-α, and the left-pawed mice tended to show a higher level after the acute stress. Chronic stress significantly upregulated the expression of hypothalamic CRH mRNA in both left-pawed and right-pawed mice. Normally, the left-pawed mice exhibited a higher GR expression in the hippocampus than the right-pawed mice. After the cat exposure, the expression of GR in both left-pawed and right-pawed mice was revealed to be greatly downregulated. Conclusion Our findings indicate that predatory stress can invoke a differential response of stressful elements in behavior-lateralized mice. Some of these responses shaped by behavioral lateralization might be helpful for facilitating adaption to various stimuli.

Myopia, a worldwide condition, is a multifactorial disease resulting in many ocular complications. Early onset of myopia has a great tendency to develop high myopia and pathological myopia later in life. The pathophysiology and progression of myopia is still unclear. Owing to its involving in visual function, optic disc and peripapillary change in high myopia can’t be neglected, and it may help in better understanding of the pathophysiology or mechanism of myopia progression. Recently, advanced imaging techniques have been developed, such as optical coherence tomography (OCT), allowing for better detecting of optic disc and peripapillary change. OCT is a high-resolution and noninvasive measurement for detection of ocular structure. Herein, we provide an updated review of optic disc and peripapillary change in OCT image, including its characteristics and clinical significance. We also propose some problems needed further investigation.

Abstract Background Methylated genes detected in sputum are promise biomarkers for lung cancer. Yet the current PCR technologies for quantification of DNA methylation and diagnostic value of the sputum biomarkers are not sufficient to be used for lung cancer early detection. The emerging droplet digital PCR (ddPCR) is a straightforward means for precise, direct, and absolute quantification of nucleic acids. Here, we investigate whether ddPCR can sensitively and robustly quantify DNA methylation in sputum for more precise diagnosis of lung cancer. Results First, the analytic performance of methylation-specific ddPCR (ddMSP) and quantitative methylation-specific PCR (qMSP) is determined in methylated and unmethylated DNA samples. Second, 29 genes, previously proposed as potential sputum biomarkers for lung cancer, are analyzed by using ddMSP in a training set of 127 lung cancer patients and 159 controls. ddMSP has higher sensitivity, precision, and reproducibility for quantification of methylation compared with qMSP (all p 0.05). The classifier has higher accuracy compared with sputum cytology (88.8 vs. 70.6%, p

Abstract Background To improve the diagnostic accuracy of distal tibiofibular syndesmoses (DTS), this study quantified the range in variations of the normal DTS in a Chinese population, based on CT scan images. Methods The study population comprised 92 patients with unilateral ankle injury. CT scans included the non-injured contralateral DTS. The position of the fibula relative to the fibular notch (incisure) of the tibia was quantified by inclusion or separation indices, based on whether the fibula was within or outside the fibular incisure, respectively. The patients were apportioned accordingly to either a DTS contained- or separate-type group (average ages 45 and 42.1 years, respectively; 19 men/26 women and 24 men/23 women). Further variations in the position of the fibula relative to the tibia were quantified with length, anterior, and posterior indices. Results The baseline characteristics of the contained- and separate-type groups were statistically comparable. The length, anterior, extra-anterior, posterior, and extra-posterior indices were successfully calculated. The anterior index of the contained group was significantly greater than that of the separated group, while the posterior index was significantly less. Conclusions This study provides measurements of the normal tibiofibular syndesmosis in a Chinese population. In individuals whose fibula lay within the fibular incisure of the tibia, the fibula was likely to be more anterior than that of individuals whose fibula lay outside the incisure. Offered as a reference, these data should improve diagnosis of injury of the DTS.

Background: There are limited data regarding prolonged extracorporeal membrane oxygenation (ECMO) support, despite increase in ECMO use and duration in patients with respiratory failure. The objective of this study was to investigate the outcomes of severe acute respiratory failure patients supported with prolonged ECMO for more than 28 days. Methods: Between January 2012 and December 2015, all consecutive adult patients with severe acute respiratory failure who underwent ECMO for respiratory support at 16 tertiary or university-affiliated hospitals in South Korea were enrolled retrospectively. The patients were divided into two groups: short-term group defined as ECMO for ⩽28 days and long-term group defined as ECMO for more than 28 days. In-hospital and 6-month mortalities were compared between the two groups. Results: A total of 487 patients received ECMO support for acute respiratory failure during the study period, and the median support duration was 8 days (4–20 days). Of these patients, 411 (84.4%) received ECMO support for ⩽28 days (short-term group), and 76 (15.6%) received support for more than 28 days (long-term group). The proportion of acute exacerbation of interstitial lung disease as a cause of respiratory failure was higher in the long-term group than in the short-term group (22.4% versus 7.5%, p

In this study, we present an analysis of warm extremes over monsoonal China (21–45° N, 106–124° E) during the last 600 years based on Chinese historical documents and simulations from the Paleoclimate Modelling Intercomparison Project Phase 3 (PMIP3) and the Coupled Model Intercomparison Project Phase 5 (CMIP5). The Chinese historical documents indicate that extreme warm records become more frequent after ~1650 CE in North China and ~1850 CE in the Yangtze River Valley. Our analyses of two threshold extreme temperature indices also illustrate that warm extremes have become more frequent since the 17th century in North China and the mid-19th century in Yangtze River Valley in good agreement with the changes in warm extremes revealed in the historical documents. This agreement suggests potential mechanisms behind the shift of periods, which should be further investigated in the future.

Background: Cerebral air embolism is defined as symptoms and signs after occlusion of cerebral arteries by intracerebral air bubble influx. There have been reports of many cases during an invasive procedure. Herein, we report a case of air embolism after thyroid biopsy. Case Report: A 70-year-old female visited our emergency room with right hemiparesis and global aphasia after thyroid biopsy. Brain computed tomography (CT) and magnetic resonance imaging revealed cerebral air embolism in the left hemisphere, and neck CT revealed air embolism in the left lower lateral neck and mediastinum. She was diagnosed with cerebral air embolism following thyroid biopsy and was treated with high-flow oxygen supply. Conclusion: Our case showed a good outcome with brain imaging and clinical symptoms due to immediate diagnosis of cerebral air embolism and adequate treatment with high-flow oxygen therapy in a patient who had presented with neurologic symptoms directly after thyroid biopsy.

There is no well-stated practical guideline for mechanically ventilated patients with or without acute respiratory distress syndrome (ARDS). We generate strong (1) and weak (2) grade of recommendations based on high (A), moderate (B) and low (C) grade in the quality of evidence. In patients with ARDS, we recommend low tidal volume ventilation (1A) and prone position if it is not contraindicated (1B) to reduce their mortality. However, we did not support high-frequency oscillatory ventilation (1B) and inhaled nitric oxide (1A) as a standard treatment. We also suggest high positive end-expiratory pressure (2B), extracorporeal membrane oxygenation as a rescue therapy (2C), and neuromuscular blockage for 48 hours after starting mechanical ventilation (2B). The application of recruitment maneuver may reduce mortality (2B), however, the use of systemic steroids cannot reduce mortality (2B). In mechanically ventilated patients, we recommend light sedation (1B) and low tidal volume even without ARDS (1B) and suggest lung protective ventilation strategy during the operation to lower the incidence of lung complications including ARDS (2B). Early tracheostomy in mechanically ventilated patients can be performed only in limited patients (2A). In conclusion, of 12 recommendations, nine were in the management of ARDS, and three for mechanically ventilated patients.

It is uncommon for tire explosion related injuries on the lower extremity. The bilateral lower extremities were injured by tire explosion when the patient was seated in a bus. She sustained an open fracture with partial bone loss in the right calcaneus (a comminuted fracture in the right ankle joint) and a closed comminuted fracture in the left tibia and fibula. This damage was caused by uncontacted tire explosion, thanks to a thick floor between the exploded tire and the patient's feet. This type of injury on lower extremity caused by uncontacted tire explosion was uncommon.

The North China Famine of 1876–1879, known in Chinese as the Dingwu qihuang (丁戊奇荒), is a famous case of drought-induced famine in Chinese history. The purpose of this paper is to provide empirical and historical evidence for understanding the impacts of extreme climate events and major disasters and the mechanisms of adaptation. From the aspects of famine-related migration and the allocation of relief money and grain, the regional interactions in social responses to extreme climate events were analyzed. This paper collected 186 records from historical documents. Regarding the regions as the nodes and the relationships between regions as the links, the spatial patterns of famine-related migration and the allocation of money and grain from 1877 to 1878 were rebuilt. The results show that, firstly, famine-related migration appeared to be spontaneous and short-distanced, with the flow mainly spreading to the surrounding areas and towns. Secondly, as a state administrative action, the relief money and grain from the non-disaster areas were distributed to the disaster areas. However, the distribution of relief grain affected the equilibrium of the food market in non-disaster areas, which led to fluctuations in food prices.

Rhein, an anthraquinone compound existing in many traditional herbal medicines, has anti-inflammatory, antioxidant, antitumor, antiviral, hepatoprotective, and nephroprotective activities, but its anti-influenza A virus (IAV) activity is ambiguous. In the present study, through plaque inhibition assay, time-of-addition assay, antioxidant assay, qRT-PCR, ELISA, and western blotting assays, we investigated the anti-IAV effect and mechanism of action of rhein in vitro and in vivo. The results showed that rhein could significantly inhibit IAV adsorption and replication, decrease IAV-induced oxidative stress, activations of TLR4, Akt, p38, JNK MAPK, and NF-κB pathways, and production of inflammatory cytokines and matrix metalloproteinases in vitro. Oxidant H2O2 and agonists of TLR4, Akt, p38/JNK and IKK/NF-κB could significantly antagonize the inhibitory effects of rhein on IAV-induced cytopathic effect (CPE) and IAV replication. Through an in vivo test in mice, we also found that rhein could significantly improve the survival rate, lung index, pulmonary cytokines, and pulmonary histopathological changes. Rhein also significantly decreased pulmonary viral load at a high dose. In conclusion, rhein can inhibit IAV adsorption and replication, and the mechanism of action to inhibit IAV replication may be due to its ability to suppress IAV-induced oxidative stress and activations of TLR4, Akt, p38, JNK MAPK, and NF-κB signal pathways.

ObjectivesVoice and speech alternations that can occur after total thyroidectomy are usually due to recurrent or superior laryngeal nerve injury. These alterations may also be associated with other extralaryngeal factors, such as neck muscle dysfunction and scar contracture of the neck. We performed a prospective acoustic analysis on speech changes after surgery, in the absence of laryngeal nerve injury.MethodsPatients aged 19 to 58 years undergoing total thyroidectomy, in the absence of laryngeal/pulmonary disease, previous neck surgery, or other malignant diseases, were recruited prospectively. For the running speech analysis, the speaking fundamental frequencies (SFo), range of SFo and speaking intensity were evaluated before surgery, 7 days, and 1 and 3 months after surgery. For consonant analysis, the acoustic distinctions of stop consonant, the voice onset time (VOT), vowel duration and closure duration were evaluated at the same periods.ResultsSFo and range of SFo were specifically diminished after surgery, while speaking intensities were not changed significantly after surgery. The thyroidectomized speakers displayed systematically varied VOT for the consonant production, which was phonetically representative. However, VOT after surgery could be longer in the strong aspirated and glottalized stops, but not in the lax stop than before surgery. The vowel and closure durations were not affected before and after surgery.ConclusionPatients with thyroidectomy have some difficulty of pitch control and consonant articulation during speaking. VOT is also one of the meaningful acoustic parameters and provide a reference for comparing acoustic measures before and after thyroidectomy.

Purpose: Early diagnosis and prompt treatment of acute acalculous cholecystitis is important, because it is associated with high mortality. In major trauma patients, besides the direct damage the trauma itself causes, many complications can occur due to trauma. The purpose of this study was to evaluate the prevalence and risk factors for development of acute acalculous cholecystitis in patients with severe traumatic injuries. Methods: In this retrospective study, we reviewed the trauma registry data of 629 major trauma patients (injury severity score>15) of Eulji University Hospital seen between May 2012 and March 2015. Of the 629 patients, twelve were diagnosed with acute acalculous cholecystitis. Information collected from the medical record review included demographic data, clinical characteristics, laboratory findings, and diagnostic and therapeutic outcomes. Results: Twelve patients of 629 patients (1.9%) were diagnosed with acute acalculous cholecystitis, and while nine patients survived, three patients died. The clinical and laboratory findings at the initial emergency room visit and at diagnosis of acute acalculous cholecystitis were compared, and there were significant differences in the body temperature (p=0.002), C-reactive protein (CRP) (p=0.002), alkaline phosphatase (ALP) (p=0.008), total bilirubin (p=0.015), and lactate (p=0.046). Conclusion: Early diagnosis and proper treatment is important in acute acalculous cholecystitis after major trauma. If the patients after major trauma have elevated body temperature, lactate, CRP, ALP, and total bilirubin, one should keep in mind of the possibility of acute acalculous cholecystitis.

Salvia miltiorrhiza Bunge has been reported to possess excellent antifibrotic activity. In this study, we have investigated the effect and mechanism of tanshinone IIA (Tan-IIA), salvianolic acid A (Sal-A) and salvianolic acid B (Sal-B), the important active compounds of Salvia miltiorrhiza Bunge, on areca nut extract (ANE)-induced oral submucous fibrosis (OSF) in vitro. Through human procollagen gene promoter luciferase reporter plasmid assay, hydroxyproline assay, gelatin zymography assay, qRT-PCR, ELISA and Western blot assay, the influence of these three compounds on ANE-stimulated cell viability, collagen accumulation, procollagen gene transcription, MMP-2/-9 activity, MMP-1/-13 and TIMP-1/-2 expression, cytokine secretion and the activation of PI3K/AKT, ERK/JNK/p38 MAPK and TGF-β/Smads pathways were detected. The results showed that Tan-IIA, Sal-A and Sal-B could significantly inhibit the ANE-stimulated abnormal viability and collagen accumulation of mice oral mucosal fibroblasts (MOMFs), inhibit the transcription of procollagen gene COL1A1 and COL3A1, increase MMP-2/-9 activity, decrease TIMP-1/-2 expression and inhibit the transcription and release of CTGF, TGF-β1, IL-6 and TNF-α; Tan-IIA, Sal-A and Sal-B also inhibited the ANE-induced activation of AKT and ERK MAPK pathways in MOMFs and the activation of TGF-β/Smads pathway in HaCaT cells. In conclusion, Tan-IIA, Sal-A and Sal-B possess excellent antifibrotic activity in vitro and can possibly be used to promote the rehabilitation of OSF patients.

Despite recent advances in methods for culturing Mycobacterium tuberculosis (MTB), the diagnostic yield of tuberculous pleural effusion (TBPE) remains unsatisfactory. However, unlike repeated sputum cultures of pulmonary tuberculosis, little is known about the role of repeated pleural cultures. We examined whether repeated pleural cultures are associated with increased MTB yield from TBPE.A multicenter, retrospective cohort study was performed from January 2012 to December 2015 in South Korea. Patients were categorized into two groups: single- or repeated-culture groups. The diagnostic yield of MTB and clinical, radiological, and pleural fluid characteristics were evaluated.Among the 329 patients with TBPE, 77 (23.4%) had repeated cultures and 252 (76.5%) had a single culture. Pleural culture was performed twice in all 77 patients in the repeated-culture group at a 1-day interval (inter-quartile range, 1.0-2.0). In the repeated-culture group, the yield of MTB from the first culture was 31.2%, which was similar to that in the single-culture group (31.2% vs. 29.8%, P = 0.887). However, the yield of MTB from the second culture (10/77, 13.0%) was more than that from the first. These results may be attributable to the insufficient immune clearance for MTB invasion into the pleural space between the first and second cultures. Over time, the yield of the second cultures decreased from 17.4% to 6.7% and then 6.3%. Finally, the overall yield of MTB in the repeated- and single-culture groups was 44.2% and 29.8% respectively (P < 0.001).The results showed that repeated pleural cultures increased MTB yield from TBPE in human immunodeficiency virus-negative individuals. Furthermore, repeated cultures may increase yield when carried out for two consecutive days.

Purpose: Lymph node metastasis is a stage-determining factor and the most important prognostic factor for colon cancer patients. We aimed to verify the influence of the aspects of lymph node metastatic level on the prognosis of the stage III colon cancer patients. Methods: We studied the survival rate of ninety-eight patients with stage III colon cancer who underwent an open and laparoscopic surgery at Eulji University Hospital from November 1998 to December 2009. We evaluated the survival rate and prognostic factors including the level of positive lymph node and additional factors. The level of positive lymph node was classified as either level I (pericolic and intermediate lymph node metastasis) or level II (apical lymph node metastasis). Results: The average age of the patients was 62.7 years (range, 30 to 89 years) old and the mean follow-up period was 45.9 months (range, 2 to 129 months). The comparison of the survival rates based on the level of lymph nodes shows that level I was 89.5% while level II was 41.7% (P=0.002). Multivariate analysis showed that level of positive lymph node was a significant prognostic factor. Conclusion: In this study, the level of lymph node metastasis in stage III colon cancer was significant prognostic factor. Therefore, exact evaluation and further treatment plans should be determined based on clear analysis of various aspects of the lymph nodes acquired by accurate and meticulous surgery.

Strabismus associated with high myopia is a rare abnormality of ocular motility, leading to the impairment of abduction and supraduction. Loop myopexy of the superior rectus (SR) and lateral rectus (LR) muscles is now the most preferred surgery for restoring the dislocated eye globe back into the muscle cone. Various procedural modifications have been made based on this concept, and satisfactory outcomes have been reached in most cases. In this paper, we review various surgical modifications published in the literature that are based on the loop myopexy surgery in patients with high myopic strabismus and summarize the applicable scope of different surgical procedures for patients with different degrees of strabismus. Three major surgical procedures are identified and different modifications have been applied based on their concept. Most of these modifications have been proven to be safe and effective and result in good ocular alignments. The selection of such modifications is of great importance in different patients. Careful evaluation before surgery should be made not only to make the correct diagnosis but also to choose an appropriate surgical procedure and offer individualized modifications in the surgery.

Load curve data from advanced metering infrastructure record the consumers’ behavior. User consumption models help one understand a more intelligent power provisioning and clustering the load data is one of the popular approaches for building these models. Similarity measurements are important in the clustering model, but, load curve data is a time series style data, and traditional measurement methods are not suitable for load curve data. To cluster the load curve data more accurately, this paper applied an enhanced Pearson similarity for load curve data clustering. Our method introduces the ‘trend alteration point’ concept and integrates it with the Pearson similarity. By introducing a weight for Pearson distance, this method helps to keep the whole contour of the load data and the partial similarity. Based on the weighed Pearson distance, a weighed Pearson-based hierarchy clustering algorithm is proposed. Years of load curve data are used for evaluation. Several user consumption models are found and analyzed. Results show that the proposed method improves the accuracy of load data clustering.

A retrospective analysis of patients diagnosed with tetanus was conducted to evaluate the occurrence of Guillain–Barré syndrome (GBS). Two of 13 tetanus cases were complicated with GBS. Their symptoms and signs related to GBS improved markedly after a 5-day infusion of intravenous immunoglobulin. Physicians should keep in mind that GBS can be an important cause of muscle weakness in patients with tetanus.

Laryngeal amyloidosis is uncommon and poorly understood, with limited long-term studies. Although primary localized laryngeal amyloidosis is extremely rare, it frequently involves the ventricles and the false and true vocal cords. We present a 58-year-old woman with localized laryngeal amyloidosis who presented no symptoms. On indirect laryngoscopic examination, the mass involved both arytenoids only, and had a likeness to a "boxer glove." She was treated surgically by microlaryngoscopy under general anesthesia and the mass was excised using a carbon dioxide laser. We present this case and a review of literature.

Lasting activations of toll-like receptors (TLRs), MAPK and NF-κB pathways can support influenza A virus (IAV) infection and promote pneumonia. In this study, we have investigated the effect and mechanism of action of emodin on IAV infection using qRT-PCR, western blotting, ELISA, Nrf2 luciferase reporter, siRNA and plaque inhibition assays. The results showed that emodin could significantly inhibit IAV (ST169, H1N1) replication, reduce IAV-induced expressions of TLR2/3/4/7, MyD88 and TRAF6, decrease IAV-induced phosphorylations of p38/JNK MAPK and nuclear translocation of NF-κB p65. Emodin also activated the Nrf2 pathway, decreased ROS levels, increased GSH levelss and GSH/GSSG ratio, and upregulated the activities of SOD, GR, CAT and GSH-Px after IAV infection. Suppression of Nrf2 via siRNA markedly blocked the inhibitory effects of emodin on IAV-induced activations of TLR4, p38/JNK, and NF-κB pathways and on IAV-induced production of IL-1β, IL-6 and expression of IAV M2 protein. Emodin also dramatically increased the survival rate of mice, reduced lung edema, pulmonary viral titer and inflammatory cytokines, and improved lung histopathological changes. In conclusion, emodin can inhibit IAV replication and influenza viral pneumonia, at least in part, by activating Nrf2 signaling and inhibiting IAV-induced activations of the TLR4, p38/JNK MAPK and NF-κB pathways.

Cardiomyocytes are quite resistant to gene transfer using standard techniques. We developed an expression vector carrying an attenuated but infectious and replicative coxsackievirus B3 (CVB3) genome, and unique ClaI-StuI cloning sites for an exogenous gene, whose product can be released from the nascent viral polyprotein by 2A(pro) cleavage. This vector was tested as an expression vehicle for green fluorescent protein (GFP). The vector transiently expressed GFP in cell cultures for at least ten passages and delivered functional GFP to the infected cardiomyocytes for at least 6 days. Moreover, the recombinant viruses showed virulence attenuation in vitro and in vivo. The findings suggest that the recombinant CVB3 vector could be a useful tool for viral tracking study and delivering exogenous proteins to cardiomyocytes.

Classical approaches to immunotherapy that show promise in some malignancies have generally been disappointing when applied to high-grade brain tumors such as glioblastoma multiforme (GBM). We recently showed that ex vivo expanded/activated γδ T cells recognize NKG2D ligands expressed on malignant glioma and are cytotoxic to glioma cell lines and primary GBM explants. In addition, γδ T cells extend survival and slow tumor progression when administered to immunodeficient mice with intracranial human glioma xenografts. We now show that temozolomide (TMZ), a principal chemotherapeutic agent used to treat GBM, increases the expression of stress-associated NKG2D ligands on TMZ-resistant glioma cells, potentially rendering them vulnerable to γδ T cell recognition and lysis. TMZ is also highly toxic to γδ T cells, however, and to overcome this cytotoxic effect γδ T cells were genetically modified using a lentiviral vector encoding the DNA repair enzyme O(6)-alkylguanine DNA alkyltransferase (AGT) from the O(6)-methylguanine methyltransferase (MGMT) cDNA, which confers resistance to TMZ. Genetic modification of γδ T cells did not alter their phenotype or their cytotoxicity against GBM target cells. Importantly, gene modified γδ T cells showed greater cytotoxicity to two TMZ resistant GBM cell lines, U373(TMZ-R) and SNB-19(TMZ-R) cells, in the presence of TMZ than unmodified cells, suggesting that TMZ exposed more receptors for γδ T cell-targeted lysis. Therefore, TMZ resistant γδ T cells can be generated without impairing their anti-tumor functions in the presence of high concentrations of TMZ. These results provide a mechanistic basis for combining chemotherapy and γδ T cell-based drug resistant cellular immunotherapy to treat GBM.

Vδ2(neg) γδ T cells, of which Vδ1+ γδ T cells are by far the largest subset, are important effectors against CMV infection. Malignant gliomas often contain CMV genetic material and proteins, and evidence exists that CMV infection may be associated with initiation and/or progression of glioblastoma multiforme (GBM). We sought to determine if Vδ1+ γδ T cells were cytotoxic to GBM and the extent to which their cytotoxicity was CMV dependent. We examined the cytotoxic effect of ex vivo expanded/activated Vδ1+ γδ T cells from healthy CMV seropositive and CMV seronegative donors on unmanipulated and CMV-infected established GBM cell lines and cell lines developed from short- term culture of primary tumors. Expanded/activated Vδ1+ T cells killed CMV-negative U251, U87, and U373 GBM cell lines and two primary tumor explants regardless of the serologic status of the donor. Experimental CMV infection did not increase Vδ1+ T cell--mediated cytotoxicity and in some cases the cell lines were more resistant to lysis when infected with CMV. Flow cytometry analysis of CMV-infected cell lines revealed down-regulation of the NKG2D ligands ULBP-2, and ULBP-3 as well as MICA/B in CMV-infected cells. These studies show that ex vivo expanded/activated Vδ1+ γδ T cells readily recognize and kill established GBM cell lines and primary tumor-derived GBM cells regardless of whether CMV infection is present, however, CMV may enhance the resistance GBM cell lines to innate recognition possibly contributing to the poor immunogenicity of GBM.