Visual Snow Syndrome Improves With Modulation of Resting-State Functional MRI Connectivity After Mindfulness-Based Cognitive Therapy: An Open-Label Feasibility Study.

BACKGROUND: Visual snow syndrome (VSS) is associated with functional connectivity (FC) dysregulation of visual networks (VNs). We hypothesized that mindfulness-based cognitive therapy, customized for visual symptoms (MBCT-vision), can treat VSS and modulate dysfunctional VNs. METHODS: An open-label feasibility study for an 8-week MBCT-vision treatment program was conducted. Primary (symptom severity; impact on daily life) and secondary (WHO-5; CORE-10) outcomes at Week 9 and Week 20 were compared with baseline. Secondary MRI outcomes in a subcohort compared resting-state functional and diffusion MRI between baseline and Week 20. RESULTS: Twenty-one participants (14 male participants, median 30 years, range 22-56 years) recruited from January 2020 to October 2021. Two (9.5%) dropped out. Self-rated symptom severity (0-10) improved: baseline (median [interquartile range (IQR)] 7 [6-8]) vs Week 9 (5.5 [3-7], P = 0.015) and Week 20 (4 [3-6], P < 0.001), respectively. Self-rated impact of symptoms on daily life (0-10) improved: baseline (6 [5-8]) vs Week 9 (4 [2-5], P = 0.003) and Week 20 (2 [1-3], P < 0.001), respectively. WHO-5 Wellbeing (0-100) improved: baseline (median [IQR] 52 [36-56]) vs Week 9 (median 64 [47-80], P = 0.001) and Week 20 (68 [48-76], P < 0.001), respectively. CORE-10 Distress (0-40) improved: baseline (15 [12-20]) vs Week 9 (12.5 [11-16.5], P = 0.003) and Week 20 (11 [10-14], P = 0.003), respectively. Within-subject fMRI analysis found reductions between baseline and Week 20, within VN-related FC in the i) left lateral occipital cortex (size = 82 mL, familywise error [FWE]-corrected P value = 0.006) and ii) left cerebellar lobules VIIb/VIII (size = 65 mL, FWE-corrected P value = 0.02), and increases within VN-related FC in the precuneus/posterior cingulate cortex (size = 69 mL, cluster-level FWE-corrected P value = 0.02). CONCLUSIONS: MBCT-vision was a feasible treatment for VSS, improved symptoms and modulated FC of VNs. This study also showed proof-of-concept for intensive mindfulness interventions in the treatment of neurological conditions.

Facilitators and Barriers to Weight Loss Among Patients With Idiopathic Intracranial Hypertension.

BACKGROUND: Little is known about motivation for weight loss and barriers to weight loss among patients with idiopathic intracranial hypertension (IIH). Such information is crucial for developing tailored weight management recommendations and novel interventions. METHODS: We administered a survey to patients with IIH presenting to neuro-ophthalmology clinics at The University of Michigan Kellogg Eye Center (Michigan, USA) and St. Thomas' Hospital (London, England). Participants rated importance and motivation to lose weight (1-10 scale; 10 = extremely important/motivated). Facilitators and barriers to weight loss were assessed using open-ended survey questions informed by motivational interviewing methodology. Open-ended responses were coded by 2 team members independently using a modified grounded theory approach. Demographic data were extracted from medical records. Descriptive statistics were used to analyze quantitative responses. RESULTS: Of the 221 (43 Michigan and 178 London) patients with IIH (Table 1), most were female (n = 40 [93.0%] Michigan and n = 167 [94.9%] London). The majority of patients in the United States were White (n = 35 [81.4%] Michigan), and the plurality were Black in the United Kingdom (n = 67 [37.6%] London]) with a mean (SD) BMI of 38.9 kg/m2 (10.6 kg/m2) Michigan and 37.5 kg/m2 (7.7 kg/m2) London. Participants' mean (SD) level of importance to lose weight was 8.5 (2.2) (8.1 [2.3] Michigan and 8.8 [2.1] London), but their mean (SD) level of motivation to lose weight was 7.2 (2.2) (6.8 [2.4] Michigan and 7.4 [2.1] London). Nine themes emerged from the 992 open-ended coded survey responses grouped into 3 actionable categories: self-efficacy, professional resources (weight loss tools, diet, physical activity level, mental health, and physical health), and external factors (physical/environmental conditions, social influences, and time constraints). Most responses (55.6%; n = 551) were about barriers to weight loss. Lack of self-efficacy was the most discussed single barrier (N = 126; 22.9% total, 28.9% Michigan, and 20.4% London) and facilitator (N = 77; 17.5% total, 15.9% Michigan, and 18.7% London) to weight loss. Other common barriers were related to physical activity level (N = 79; 14.3% total, 13.2% Michigan, and 14.8% London) and diet (N = 79; 14.3% total, 9.4% Michigan, and 16.3% London). Commonly reported facilitators included improvements in physical activity level (N = 73; 16.6% total, 18.5% Michigan, and 15.1% London) and dietary changes (N = 76; 17.2% total, 16.4% Michigan, and 17.9% London). CONCLUSIONS: Patients with IIH believe weight loss is important. Self-efficacy was the single most mentioned important patient-identified barrier or facilitator of weight loss, but professional resource needs and external factors vary widely at the individual level. These factors should be assessed to guide selection of weight loss interventions that are tailored to individual patients with IIH.

Remodeling of the neuromuscular junction in myasthenia gravis increases serum neurofilament heavy chain levels.

INTRODUCTION/AIMS: In myasthenia gravis, prolonged muscle denervation causes muscle atrophy. We re-visited this observation using a biomarker hypothesis. We tested if serum neurofilament heavy chain levels, a biomarker for axonal degeneration, were elevated in myasthenia gravis. METHODS: We enrolled 70 patients with isolated ocular myasthenia gravis and 74 controls recruited from patients in the emergency department. Demographic data were collected alongside serum samples. Serum samples were analyzed by enzyme-linked immunosorbent assay (ELISA) for the neurofilament heavy chain (NfH-SMI35). The statistical analyses included group comparisons, receiver operator characteristic (ROC) curves, area under the curve (AUC), sensitivity, specificity, and positive and negative predictive values. RESULTS: Serum neurofilament heavy chain levels were significantly (p < 0.0001) higher in individuals with myasthenia gravis (0.19 ng/mL) than in healthy control subjects (0.07 ng/mL). A ROC AUC optimized cutoff level of 0.06 ng/mL gave a diagnostic sensitivity of 82%, specificity of 76%, positive predictive value of 0.77 and a negative predictive value of 0.81. DISCUSSION: The increase of serum neurofilament heavy chain levels in myasthenia gravis is consistent with observations of muscle denervation. We suggest that there is ongoing remodeling of the neuromuscular junction in myasthenia gravis. Longitudinal quantification of neurofilament isoform levels will be needed to investigate the prognostic value and potentially guide treatment decisions.

[A real world study of anti-IgE monoclonal antibody in the treatment of allergic united airway disease].

Objective: To investigate the clinical efficacy and safety of anti-IgE monoclonal antibody (omazumab) in the treatment of allergic united airway disease (UAD) in the real-wold. Methods: Retrospective cohort study summarizes the case data of patients with allergic united airway disease who were treated with anti IgE monoclonal antibody (omalizumab) for more than 16 weeks from March 1, 2018 to June 30, 2022 in the Peking University First Hospital.The allergic UAD is defined as allergic asthma combined with allergic rhinitis (AA+AR) or allergic asthma combined with chronic sinusitis with nasal polyps (AA+CRSwNP) or allergic asthma combined with allergic rhinitis and nasal polyps (AA+AR+CRSwNP). The control of asthma was evaluated by asthma control test (ACT), lung function test and fractional exhaled nitric oxide (FeNO). The AR was assessed by total nasal symptom score (TNSS). The CRSwNP was evaluated by nasal visual analogue scale (n-VAS), sino-nasal outcome test-22 (SNOT-22), nasal polyps score (TPS) and Lund-Mackay sinus CT grading system. The global evaluation of omalizumab for the treatment of allergic UADwas performed by Global Evaluation of Treatment Effectiveness(GETE).The drug-related side effects were also recorded. Matched t test and Wilcoxon signed-rank test were used to compare the score changes of IgE monoclonal antibody (omazumab) before and after treatment, and multivariate logistic regression analysis was used to determine the influencing factors of IgE monoclonal antibody (omazumab) response. Results: A total of 117 patients with UAD were enrolled, ranging in age from 19 to 77 years; The median age of patients was 48.7 years; Among them, 60 were male, ranging from 19 to 77 years old, with a median age of 49.9 years; There were 57 females, ranging from 19 to 68 years old, with a median age of 47.2 years. There were 32 cases in AA+AR subgroup, 59 cases in AA+CRSwNP subgroup, and 26 cases in AA+AR+CRSwNP subgroup. The total serum IgE level was 190.5 (103.8,391.3) IU/ml. The treatment course of anti IgE monoclonal antibody was 24 (16, 32) weeks. Compared with pre-treatment, omalizumab increased ACT from 20.0 (19.5,22.0) to 24.0 (23.0,25.0) (Z=-8.537, P<0.001), increased pre-bronchodilator FEV1 from 90.2 (74.8,103.0)% predicted value to 95.4 (83.2,106.0)% predicted value (Z=-5.315,P<0.001), increased FEV1/FVC from 80.20 (66.83,88.38)% to 82.72 (71.26,92.25)% (Z=-4.483,P<0.001), decreased FeNO from(49.1±24.8) ppb to (32.8±24.4) ppb (t=5.235, P<0.001), decreased TNSS from (6.5±2.6)to (2.4±1.9) (t=14.171, P<0.001), decreased n-VAS from (6.8±1.2) to (3.4±2.0)(t=14.448, P<0.001), decreased SNOT-22 from (40.0±7.9) to (21.3±10.2)(t=15.360, P<0.001), decreased TPS from (4.1±0.8) to (2.4±1.0)(t=14.718, P<0.001) and decreased Lund-Mackay CT score from (6.0±1.3) to (3.1±1.6)(t=17.012, P<0.001). The global response rate to omalizumab was 67.5%(79/117). The response rate in AA+AR (90.6%,29/32) was significantly higher than that in AA+CRSwNP (61.0%,36/59) and AA+AR+CRSwNP (53.8%,14/26) subgroups (χ2=11.144,P=0.004). Only 4 patients (3.4%,4/117) had mild side effects. Conclusion: The real-world study showed favorable effectiveness and safety of anti-IgE monoclonal antibody for treatment of allergic UAD. To provide basis for preventing the progress and precise treatment of allergic UAD.

[Research progress of influenza vaccination, pneumococcal vaccination and COVID-19 vaccination among cancer patients].

This article reviews the relevant studies on the efficacy and safety of influenza, pneumococcal and COVID-19 vaccination among tumor patients worldwide in recent years. By combing and analyzing the retrieved literature, the results show that influenza and pneumococcal vaccination can significantly reduce the morbidity and hospitalization rate of infectious diseases in tumor patients, reduce the risk of cardiovascular events and death, and significantly improve survival prognosis. COVID-19 vaccination can also protect tumor patients, especially those who have completed full dose vaccination. Authoritative guidelines and consensuses worldwide all recommend that tumor patients receive influenza, pneumococcal and COVID-19 vaccines. We should carry out relevant researches, as well as take effective measures to strengthen patient education, so that tumor patients can fully experience the health protection brought by the vaccine to this specific group.

Dr Gordon Plant's Festschrift Tidings.

We came together in March 2021 for a joyous celebration of Dr Gordon Plant's incredible career. This is a report of the meeting tidings.

[Aspirin-exacerbated respiratory disease treated with omalizumab: 3 cases report and literature review].

Objective: To summarize the clinical data of aspirin-exacerbated respiratory disease (AERD) treated with omalizumab in Peking University First Hospital and reviewed the relative literatures. Methods: We analyzed retrospectively the clinical data of three cases of AERD treated with omalizumab in Peking University First Hospital from March 1, 2018 to December 31, 2021. The clinical researches on the treatment of AERD with omalizumab up to January 31, 2022 were retrieved in PubMed, China National Knowledge Infrastructure (CNKI) and Wanfang Data. Results: Our three patients of AERD treated with omalizumab for 32 to 68 weeks obtained relief of symptoms of upper and lower respiratory tract, improvement in lung function, and reduction in percentage of blood eosinophils. There were 14 clinical studies on treatment of AERD with omalizumab, including 3 randomized, double-blind and placebo-controlled studies and 11 self-controlled case series studies. The majority of studies showed that omalizumab contributed to improve the symptoms of AERD, decrease the frequency of asthma attacks and reduce systemic glucocorticoid use. Conclusion: Omalizumab can improve the disease control of AERD, but further studies are needed.

[Effects of low level laser irradiation on the osteogenic capacity of sodium alginate/gelatin/human adipose-derived stem cells 3D bio-printing construct].

OBJECTIVE: To explore the effects of low level laser irradiation (LLLI) on the osteogenic capacity of three-dimensional (3D) structure by 3D bio-printing construct used human adipose-derived stem cells (hASCs) as seed cells. METHODS: Using hASCs as seed cells, we prepared sodium alginate/gelatin/hASCs 3D bio-printing construct, and divided them into four groups: PM (proliferative medium), PM+LLLI, OM (osteogenic medium) and OM+LLLI, and the total doses of LLLI was 4 J/cm². Immunofluorescence microscopy was used to observe the viability of the cells, and analyze the expression of the osteogenesis-related protein Runt-related transcription factor 2 (Runx2) and osteocalcin (OCN). RESULTS: The 3D constructs obtained by printing were examined by microscope. The sizes of these 3D constructs were 10 mm×10 mm×1.5 mm. The wall thickness of the printed gelatin mold was approximately 1 mm, and the pores were round and had a diameter of about 700 µm. The cell viability of sodium alginate/gelatin/hASCs 3D bio-printing construct was high, and the difference among the four groups was not significant. On day 7, the expression of OCN from high to low was group OM+LLLI, PM+LLLI, OM and PM. There were significant differences among these groups (P<0.01), but there was no significant difference between group PM+LLLI and OM. On day 14, the expression of OCN in each group was higher than that on day 7, and there was no significant difference between group OM+LLLI and OM. The expression of Runx2 in group OM+LLLI was more than 90%, significantly higher than that in group OM (P<0.01). But the expression of Runx2 in group PM+LLLI and OM+LLLI were significantly lower than that in the non-irradiated groups. The expression of osteogenesis-related protein Runx2 and OCN were higher in OM groups than in PM groups. Furthermore, the irradiated groups were significantly higher than the non-irradiated groups. CONCLUSION: LLLI does not affect the cell viability of sodium alginate/gelatin/hASCs 3D bio-printing construct, and may promote the osteogenic differentiation of hASCs.

[Effect of low-level laser irradiation on proliferation and osteogenic differentiation of human adipose-derived stromal cells].

OBJECTIVE: To examine the in vitro effects of low-level laser irradiation (LLLI) on proliferation and differentiation of human adipose-derived stromal cells (hASCs). METHODS: Cultured cells were exposed to different doses of LLLI with a semiconductor diode laser (980 nm; 100 mW-12 W power output). The effects of laser on proliferation were assessed daily up to seven days of culture in cells irradiated for four consecutive days with laser doses of 2, 4, 6 or 8 J/cm2, the cells without irradiation were used as controls. Half of the cells were changed to osteogenic medium (OM) when they had grown to 70% confluence. The hASCs both with and without osteogenic supplements were divided into three groups, and each group was irradiated at doses of 0, 2 and 4 J/cm2. In order to examine the in vitro effects of LLLI on osteogenic differentiation of hASCs, the alkaline phosphatase activity was assessed on day 7, and alizarin red staining (AR-S) and quantitative detection were assessed on days 14 and 21. The expression of osteoblast master genes (ALP and Runx2) were tested on days 7 and 14. RESULTS: The proliferation medium(PM)+LLLI4 J/cm2 group had the highest multiplication rate. In the groups with osteogenic supplements, LLLI increased alkaline phosphatase activity and mineralized nodule formation, and stimulated the expression of ALP and Runx2. Furthermore, the effect became more obvious at high dose. CONCLUSION: Our data demonstrated that hASCs proliferation and osteogenic differentiation were enhanced by LLLI. With the increase of laser dose, the effect of LLLI would be enhanced at first, and then be decreased after reaching a peak.

Resveratrol improves delayed r-tPA treatment outcome by reducing MMPs.

OBJECTIVES: Although recombinant tissue plasminogen activator (r-tPA) is currently the most effective treatment for brain ischemic stroke, the 3-h narrow therapeutic windows severely limits its clinical efficacy. We aim to investigate the effect of resveratrol on improving treatment outcomes of delayed r-tPA administration. MATERIALS & METHODS: Patients were randomly divided according to their onset-to-treatment time (OTT), as early OTT or delayed OTT. Then, they were either treated with r-tPA + placebo or with r-tPA + resveratrol. Twenty-four hours after the treatment, outcomes were assessed with NIH stroke scale (NIHSS), and plasma levels of MMP-2 and MMP-9 were also examined with ELISA. RESULTS: In patients receiving delayed r-tPA treatment, co-administration of resveratrol significantly improves their treatment outcomes compared with those receiving placebo, as indicated by improved NIHSS scores. This improved outcome was be caused by resveratrol-induced reduction in plasma levels of both matrix metalloproteinase (MMP)-2 and MMP-9, as a positive correlation was observed between reductions in both MMPs and patient NIHSS scores. CONCLUSIONS: Resveratrol could be potentially administered as an adjuvant with r-tPA treatment, which extends the clinical therapeutic window of r-tPA, therefore improving the outcome of patients receiving late stroke treatment.

Effect of embolic microspheres in the treatment of primary hepatic carcinoma.

The purpose of this study was to evaluate the clinical effect of embolic microspheres in the treatment of primary hepatic carcinoma. Fifty-eight patients who were confirmed with primary hepatic carcinoma by imaging were retrospectively analyzed. They were firstly perfused with 50 mg of oxaliplatin and 40 mg of epirubicin. Embolic microspheres were then injected into the distal end of targeted blood vessels. After this procedure, dynamic observation was carried out until tumor stain disappeared. Liver function and blood indexes were reexamined on days 5, 6, 7 and 28 after treatment, and moreover, the liver was examined with Magnetic Resonance Imaging (MRI) or computed tomography (CT). Compared to traditional lipiodol embolization, embolic microspheres did not aggregate the damage on liver function and the imaging examination suggested necrosis of some tumor tissues. Embolic microspheres proved to be effective in treating primary hepatic carcinoma. It produces no damage on liver function and can lead to significant shrinkage of hepatic carcinoma and necrosis of some tumor tissues. Embolic microspheres, which merely block distal branches of tumor-feeding artery, can avoid collateral circulation induced by permanent blocking, thus achieve a good treatment effect.

Ocular Myasthenia Gravis: Toward a Risk of Generalization Score and Sample Size Calculation for a Randomized Controlled Trial of Disease Modification.

BACKGROUND: There is currently no prognostic test to determine the risk of developing generalized myasthenia gravis (GMG) risk in patients who first present with ocular disease. Most studies that report risk factors are flawed by the inclusion of patients on immunosuppression, which is likely to reduce the risk. OBJECTIVE: To create a prognostic score to predict the risk of GMG. METHODS: Multicenter retrospective cohort of patients with ocular myasthenia gravis for minimum 3 months, untreated with immunosuppression for minimum 2 years or until GMG onset. RESULTS: One hundred one (57 female) patients were included, with median follow-up of 8.4 years (2-42) from disease onset. Thirty-one developed GMG at median of 1.31 years (3.5 months-20.2 years); 19 occurred within 2 years. Univariable logistic regression analysis produced 3 significant predictors (P < 0.10), adjusted odds ratios in a multivariable logistic model (χ P = 0.01) with multiple imputations for missing data: seropositivity, 5.64 (95% CI, 1.45-21.97); presence of 1 or more comorbidities including autoimmune disorders, 6.49 (95% CI, 0.78-53.90); thymic hyperplasia, 5.41 (95% CI, 0.39-75.43). Prognostic score was derived from the coefficients of the logistic model: sum of the points (1 point for the presence of each of the above predictive factors), classified "low risk" if ≤1 and "high risk" if ≥2. Predicted probabilities were 0.07 (SD, 0.03) for low risk and 0.39 (SD, 0.09) for high risk. Negative predictive value was 91% (95% CI, 79-98), positive predictive value was 38% (95% CI, 23-54), sensitivity was 79% (95% CI, 54-94), specificity was 63% (95% CI, 50-74), area under receiver operating characteristic curve was 0.74 (95% CI, 0.64-0.85). CONCLUSIONS: In this preliminary study, we have shown by proof of principle that it is possible to stratify risk of GMG: an approach that may allow us to better counsel patients at diagnosis, complement decision-making, and move us toward addressing the question of modifying GMG risk in high-risk patients. Furthermore, the effect of comorbidities is novel and demands further elucidation.

Glabridin nanosuspension for enhanced skin penetration: formulation optimization, in vitro and in vivo evaluation.

Glabridin, a polyphenolic flavonoid from licorice, has inspired great interest for its antioxidant, anti-inflammatory and skin-lightening activities. However, low water solubility and poor stability of glabridin impedes its topical application in cosmetic products and therapies of dermal diseases. The purpose of this study was to develop a nanosuspension formulation of glabridin to improve its skin permeation. Glabridin nanosuspensions were prepared using anti-solvent precipitation-homogenization method, and Box-Behnken design was adopted to investigate the effects of crucial formulation variables on particle size and to optimize the nanosuspension formulation. The optimal formulation consisted of 0.25% glabridin, 0.47% Poloxamer 188 and 0.11% Polyvinylpyrrolidone K30, and the obtained nanosuspension showed an average particle size of 149.2 nm with a polydispersity index of 0.254. Furthermore, the nanosuspension exhibited significantly enhanced drug permeation flux of glabridin through rat skin with no lag phase both in vitro and in vivo, compared to the coarse suspension and physical mixture. The glabridin nanosuspension showed no significant particle aggregates and a drug loss of 5.46% after storage for 3 months at room temperature. With its enhanced skin penetration, the nanosuspension might be a more preferable formulation for topical administration of poorly soluble glabridin.

Acquired Esotropia in Cerebellar Disease: A Case Series Illustrating Misdiagnosis as Isolated Lateral Rectus Paresis and Progression Over Time.

We highlight an under-recognised cause of acquired esotropia with this prospective observational case series of adults with diplopia secondary to cerebellar dysfunction. We also show deterioration of cerebellar esotropia over time, which has not been previously described. Seven adults (four women) developed diplopia at a median age of 63 years (range: 31-75 years), as the initial manifestation of the underlying cerebellar disorder. Causes of cerebellar dysfunction were familial cerebellar ataxia of unknown mutation (two patients), idiopathic cerebellar ataxia (four patients), and spinocerebellar ataxia 3 (one patient). At onset, three patients had unilateral and four had bilateral lateral rectus under-action. These were initially diagnosed as lateral rectus paresis, but the diagnosis was revised, as our examination showed no slowing of abducting saccades assessed clinically and full abduction with gaze-evoked nystagmus. Esotropia was concomitant and worse for distance, although at onset one patient's esotropia was equal for near and distance. There was a trend of worsening esotropia over time, following a median interval follow-up of 4 years (range: 1-18). All patients were first observed to have cerebellar eye signs after a median interval of 5 years (range: 1-30) from presentation, i.e., impaired pursuit (7/7 patients), gaze-evoked nystagmus (7/7), hypometric saccades (3/7), downbeat nystagmus (2/7), and skew deviation (4/7). Only two patients have not developed non-ocular cerebellar eye signs, after 5 and 8 years from diplopia onset, respectively; the other five patients had gait ataxia, which could be mild. The patients were successfully treated with prisms (7/7), botulinum toxin injections (1/7), and strabismus surgery (1/7).

Long non-coding RNA MALAT1 promotes tumour growth and metastasis in colorectal cancer through binding to SFPQ and releasing oncogene PTBP2 from SFPQ/PTBP2 complex.

BACKGROUND: Metastasis associated with lung adenocarcinoma transcript-1 (MALAT1) is a functional long non-coding RNA (lncRNA), which is highly expressed in several tumours, including colorectal cancer (CRC). Its biological function and mechanism in the prognosis of human CRC is still largely under investigation. METHODS: This study aimed to investigate the new effect mechanism of MALAT1 on the proliferation and migration of CRC cells in vitro and in vivo, and detect the expression of MALAT1, SFPQ (also known as PSF (PTB-associated splicing factor)), and PTBP2 (also known as PTB (polypyrimidine-tract-binding protein)) in CRC tumour tissues, followed by correlated analysis with clinicopathological parameters. RESULTS: We found that overexpression of MALAT1 could promote cell proliferation and migration in vitro, and promote tumour growth and metastasis in nude mice. The underlying mechanism was associated with tumour suppressor gene SFPQ and proto-oncogene PTBP2. In CRC, MALAT1 could bind to SFPQ, thus releasing PTBP2 from the SFPQ/PTBP2 complex. In turn, the increased SFPQ-detached PTBP2 promoted cell proliferation and migration. SFPQ critically mediated the regulatory effects of MALAT1. Moreover, in CRC tissues, MALAT1 and PTBP2 were overexpressed, both of which were associated closely with the invasion and metastasis of CRC. However, the SFPQ showed unchanged expression either in CRC tissues or adjacent normal tissues. CONCLUSIONS: Our findings implied that MALAT1 might be a potential predictor for tumour metastasis and prognosis. Furthermore, the interaction between MALAT1 and SFPQ could be a novel therapeutic target for CRC.

Ocular myasthenia gravis: controversies and updates.

The majority of patients with myasthenia gravis (MG) initially present with ocular symptoms. An unresolved question is whether there are clinical features at onset to guide clinicians to predict an individual patient's conversion risk from ocular MG (OMG) to generalized disease, or "secondary generalized MG" (SGMG), that is, a prognostic model. In light of the emerging theory that early corticosteroids may have a risk-modifying effect, the factors associated with secondary SGMG previously reported should be revisited. Studies showing potential risk-modifying effects of corticosteroids are useful, though flawed, owing to the heterogeneous retrospective studies and methods of reporting. Updates on other potential immunosuppressive agents are also discussed. Thymectomy in OMG has been recently reported in a few studies to be useful. MG associated with antibodies to muscle-specific kinase, usually associated with severe generalized MG, can cause a pure OMG syndrome. Recent serological developments in seronegative patients have also revealed antibodies to clustered anti-acetylcholine receptor and lipoprotein receptor-related protein-4.

[Analysis of influenza vaccination status and immunization strategy in high-risk population].

Influenza is a contagious respiratory disease caused by influenza viruses, and the burden of severe disease is commonly seen in high risk populations. Influenza vaccination is an effective way to prevent influenza and its complications, especially for high risk populations. Although some countries have included influenza vaccine in their national immunization programs, influenza vaccination rates remain low globally in high risk populations. The influenza vaccine in China is still a non-immunization program vaccine that is voluntarily vaccinated at its own expense, and the influenza vaccine immunization strategy is different across the country. There is still a gap between the vaccination rate of the influenza vaccine and that of developed countries. It is an urgent problem to further optimize the whole population immunization strategy of influenza vaccine in China, strengthen the publicity of the whole population immunization strategy of influenza vaccine, and reduce the disease burden of influenza in China.

Ferret lung transplant: an orthotopic model of obliterative bronchiolitis.

Obliterative bronchiolitis (OB) is the primary cause of late morbidity and mortality following lung transplantation. Current animal models do not reliably develop OB pathology. Given the similarities between ferret and human lung biology, we hypothesized an orthotopic ferret lung allograft would develop OB. Orthotopic left lower lobe transplants were successfully performed in 22 outbred domestic ferrets in the absence of immunosuppression (IS; n = 5) and presence of varying IS protocols (n = 17). CT scans were performed to evaluate the allografts. At intervals between 3-6 months the allografts were examined histologically for evidence of acute/chronic rejection. IS protects allografts from acute rejection and early graft loss. Reduction of IS dosage by 50% allowed development of controlled rejection. Allografts developed infiltrates on CT and classic histologic acute rejection and lymphocytic bronchiolitis. Cycling of IS, to induce repeated episodes of controlled rejection, promoted classic histologic hallmarks of OB including fibrosis-associated occlusion of the bronchiolar airways in all allografts of long-term survivors. In conclusion, we have developed an orthotopic lung transplant model in the ferret with documented long-term functional allograft survival. Allografts develop acute rejection and lymphocytic bronchiolitis, similar to humans. Long-term survivors develop histologic changes in the allografts that are hallmarks of OB.

12S-hydroxyeicosatetraenoic acid levels link to coronary artery disease in Type 2 diabetic patients.

BACKGROUND: 12(S)-Hydroxyeicosatetraenoic acid (12(S)-HETE) is a metabolite of arachidonic acid. 12(S)-HETE is involved in the pathogenesis of atherosclerosis and diabetes. However, the correlation between 12(S)-HETE and coronary artery disease (CAD) in the diabetic patient is unclear. AIMS: The study investigated the relationship between 12(S)-HETE and CAD in Type 2 diabetes (T2D). METHODS: Plasma 12(S)- HETE levels were detected by enzyme-linked immunosorbent assay in 103 healthy controls (control), 109 diabetic patients without CAD (diabetic), and 152 diabetic patients with CAD (diabetic-CAD). RESULTS: 12(S)-HETE levels were higher in both diabetic and diabetic-CAD groups compared to control and in the diabetic-CAD group compared to the diabetic group. In the multiple linear stepwise regression analysis, 12(S)-HETE levels correlated independently with CAD, systolic blood pressure, and glycated hemoglobin. CONCLUSIONS: These results indicate that 12(S)-HETE levels are increased in diabetic patients with CAD, suggesting a role for atherosclerosis in T2D.