Virus classification for viral genomic fragments using PhaGCN2.

Viruses are the most ubiquitous and diverse entities in the biome. Due to the rapid growth of newly identified viruses, there is an urgent need for accurate and comprehensive virus classification, particularly for novel viruses. Here, we present PhaGCN2, which can rapidly classify the taxonomy of viral sequences at the family level and supports the visualization of the associations of all families. We evaluate the performance of PhaGCN2 and compare it with the state-of-the-art virus classification tools, such as vConTACT2, CAT and VPF-Class, using the widely accepted metrics. The results show that PhaGCN2 largely improves the precision and recall of virus classification, increases the number of classifiable virus sequences in the Global Ocean Virome dataset (v2.0) by four times and classifies more than 90% of the Gut Phage Database. PhaGCN2 makes it possible to conduct high-throughput and automatic expansion of the database of the International Committee on Taxonomy of Viruses. The source code is freely available at https://github.com/KennthShang/PhaGCN2.0.

Chemotherapy re-use versus anti-angiogenic monotherapy as the third-line treatment of patients with metastatic colorectal cancer: a real-world cohort study.

BACKGROUND: There are various recommendations for third-line treatment in mCRC, however, there is no consensus on who is more suitable for particular strategy. Chemotherapy re-use in third-line setting is a common option in clinical practice. This study aimed to investigate the efficacy of third-line chemotherapy re-use by the comparison with that of anti-angiogenic monotherapy, and further find the population more suitable for third-line chemotherapy. METHODS: Using electronic medical records of patients with mCRC, a retrospective cohort study was conducted. A total of 143 patients receiving chemotherapy and 40 patients receiving anti-angiogenic monotherapy in third-line setting as control group were retrospectively collected. Baseline characteristics were analyzed using the χ² test or the Fisher's exact test. ROC curve and surv_cutpoint function of 'survminer' package in R software were used to calculate the cut-off value. Survival curves were plotted with the Kaplan-Meier method and were compared using the log-rank test. The Cox proportional hazard regression model was used to analyze the potential risk factors. RESULTS: A total of 143 patients receiving chemotherapy and 40 patients receiving anti-angiogenic monotherapy in third-line setting were retrospectively collected. Chemotherapy rechallenge was recorded in 93 patients (93/143, 65.0%), and the remaining patients chose new chemotherapeutic drugs that had not been previously used, including irinotecan-based (22/50), oxaliplatin-based (9/50), raltitrexed (9/50), gemcitabine (5/50) and other agents (5/50). The ORR and DCR of third-line chemotherapy reached 8.8%, 61.3%, respectively (anti-angiogenic monotherapy group: ORR 2.6%, DCR 47.4%). The mPFS and mOS of patients receiving chemotherapy were 4.9 and 12.0 m, respectively (anti-angiogenic monotherapy group: mPFS 2.7 m, mOS 5.2 m). Subgroup analyses found that patients with RAS/RAF mutation, longer PFS (greater than 10.6 m) in front-line treatment or larger tumor burden had better prognosis with third-line chemotherapy rather than anti-angiogenic monotherapy. CONCLUSIONS: Third-line chemotherapy re-use was effective in mCRC. Those with more aggressive characteristics (RAS/RAF mutant, larger tumor burden) or better efficacy of previous chemotherapy (longer PFS) were more appropriate for third-line chemotherapy, rather than anti-angiogenic monotherapy.

Clinical characteristics and effects of inhaled corticosteroid in patients with post-COVID-19 chronic cough during the Omicron variant outbreak.

BACKGROUND: Chronic cough is a common symptom in patients post the coronavirus disease 2019 (COVID-19). In this study, we aimed to investigate the efficacy of inhaled corticosteroids (ICS) and the clinical characteristics of patients with post-COVID-19 chronic cough during the Omicron era. METHODS: An ambispective, longitudinal cohort study was conducted that included patients with post-COVID-19 who attended the respiratory clinic at our hospital between January 1, 2023, and March 31, 2023 with a complaint of persistent cough lasting more than 8 weeks. At 30 and 60 days after the first clinic visit for post-COVID-19 chronic cough, enrolled patients were prospectively followed up. We compared the changes in symptoms and pulmonary function between patients receiving ICS treatment (ICS group) and those not receiving ICS treatment (NICS group) at the two visits. RESULTS: A total of 104 patients with post-COVID-19 chronic cough were enrolled in this study (ICS group, n = 51; NICS group, n = 53). The most common symptoms accompanying post-COVID-19 chronic cough were sputum (58.7%, 61/104) and dyspnea (48.1%, 50/104). Seventy-one (82.6%, 71/86) patients had airway hyperresponsiveness, and 49 patients (47.1%, 49/104) were newly diagnosed with asthma. Most patients (95.2%, 99/104) exhibited improvement at 60 days after the first visit. The pulmonary function parameters of the patients in the ICS group were significantly improved compared to the baseline values (P < 0.05), and the improvement in the FEV1/FVC was significantly greater than that in the NICS group (P = 0.003) after 60 days. CONCLUSIONS: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may contribute to the pathogenesis of asthma, which could be the underlying cause of persistent cough post-COVID-19 infection. Post-COVID-19 chronic cough during the Omicron era was often accompanied by sputum, dyspnea, and airway hyperresponsiveness. ICS treatment did not have a significant impact on symptom management of post-COVID-19 chronic cough; however, it can improve impaired lung function in in these individuals.

The experience of diabetic retinopathy patients during hospital-to-home full-cycle care: A qualitative study.

BACKGROUND: Diabetic retinopathy (DR) is one of the major blinding eye diseases worldwide. Psychological, emotional and social problems of DR patients are prominent. The aim of this study is to explore the experiences of patients with different phases of DR from hospital to home based on the "Timing It Right" framework, and to provide a reference for formulating corresponding intervention strategies. METHODS: The phenomenological method and semi-structured interviews were used in this study. A total of 40 patients with DR in different phases were recruited from a tertiary eye hospital between April and August 2022. Colaizzi's analysis method was used to analyse the interview data. RESULTS: Based on the "Timing It Right" framework, different experiences in five phases of DR before and after Pars Plana Vitrectomy (PPV) were extracted. The patients experienced complicated emotional reactions and inadequate coping skills during the pre-surgery phase, increased uncertainty during the post-surgery phase, insufficient confidence and the decision to change during the discharge preparation phase, eagerness for professional support and moving forward in exploration during the discharge adjustment phase, and courageous acceptance and positive integration during the discharge adaptation phase. CONCLUSION: The experiences of DR patients with vitrectomy in different phases of disease are ever-changing, and medical staff should provide personalized support and guidance to help DR patients get through the hard times smoothly and enhance the quality of hospital-family holistic care.

Practice of the training program for ophthalmic specialist nurses in Zhejiang Province of China.

AIMS: To explore the effects of training programs for ophthalmic specialist nurses in Zhejiang Province of China. METHODS: The training program included one month of theoretical training and three months of practical clinical training. The Two-Tutor system was used in training. The training contents were mainly set up around four modules: specialty knowledge and clinical skills, management, clinical teaching, and nursing research. We used theoretical examination, clinical practice assessment and trainee evaluation to assess the effectiveness of the training program. Before and after the training, the trainees' core competence was assessed by a homemade questionnaire. RESULTS: In total, 48 trainees from 7 provinces (municipalities) in China participated in the training program. All trainees passed theoretical and clinical practice examinations and trainee evaluations. Their core competencies were significantly improved after training (p < 0.05). CONCLUSION: This training program for ophthalmic specialist nurses is scientific and effective in improving nurses' ability to provide ophthalmic specialist nursing care.

Peroxisome proliferator activated receptor-γ agonist pioglitazone improves vascular and metabolic dysfunction in systemic lupus erythematosus.

OBJECTIVES: Premature cardiovascular events in systemic lupus erythematosus (SLE) contribute to morbidity and mortality, with no effective preventive strategies described to date. Immune dysregulation and metabolic disturbances appear to play prominent roles in the induction of vascular disease in SLE. The peroxisome proliferator activated receptor-gamma agonist pioglitazone (PGZ suppresses vascular damage and immune dysregulation in murine lupus and improves endothelial dysfunction in other inflammatory diseases. We hypothesised that PGZ could improve vascular dysfunction and cardiometabolic parameters in SLE. METHODS: Eighty SLE subjects with mild to severe disease activity were randomised to a sequence of PGZ followed by placebo for 3 months, or vice versa, in a double-blind, cross-over design with a 2-month wash-out period. Primary endpoints were parameters of endothelial function and arterial inflammation, measured by multimodal assessments. Additional outcome measures of disease activity, neutrophil dysregulation, metabolic disturbances and gene expression studies were performed. RESULTS: Seventy-two subjects completed the study. PGZ was associated with a significant reduction in Cardio-Ankle Vascular Index (a measure of arterial stiffness) compared with placebo. Various metabolic parameters improved with PGZ, including insulin resistance and lipoprotein profiles. Circulating neutrophil extracellular trap levels also significantly decreased with PGZ compared with placebo. Most adverse events experienced while on PGZ were mild and resolved with reduction in PGZ dose. CONCLUSION: PGZ was well tolerated and induced significant improvement in vascular stiffness and cardiometabolic parameters in SLE. The results suggest that PGZ should be further explored as a modulator of cardiovascular disease risk in SLE. TRIAL REGISTRATION NUMBER: NCT02338999.

A cycloartenol synthase from the steroidal saponin biosynthesis pathway of Paris polyphylla.

Steroidal saponins named polyphyllin are the major active components of Paris polyphylla. Cycloartenol synthase (CAS) is a key enzyme that catalyzes the formation of the sterol scaffold. In this study, we cloned a putative CAS gene from Paris polyphylla. Heterologous expression in yeast indicated that PpCAS can convert 2,3-oxidosqualene into cycloartenol. qRT-PCR analysis showed that the expression of PpCAS was highest in leaves and lowest in roots. To our best knowledge, this is the first report of the functional characterization of cycloartenol synthase from Paris polyphylla, which lays the foundation for further analysis of the biosynthesis pathway of polyphyllins.[Formula: see text].

Ectopic overexpression of a cotton plastidial Na+ transporter GhBASS5 impairs salt tolerance in Arabidopsis via increasing Na+ loading and accumulation.

MAIN CONCLUSION: GhBASS5 is a member of the bile acid sodium symporter (BASS) gene family from cotton and a plastid-localized Na+ transporter that negatively regulates salt tolerance of plants. Soil salinization is a major constraint on global cotton production, and Na+ is the most dominant toxic ion in salinity stress. Hence, insights into the identities and properties of transporters that catalyze Na+ movement between different tissues and within the cell compartments are vital to understand the salt-tolerant mechanisms of plants. Here, we identified the GhBASS5 gene, a member of the bile acid sodium symporter (BASS) gene family from cotton, served as a plastidic Na+ transporter. GhBASS5 encodes a membrane protein localized in the plastid envelope. It was highly expressed in cotton roots and predominantly existed in the vascular cylinder. Heterogenous expression of GhBASS5 in Arabidopsis chloroplasts promoted Na+ uptake into chloroplasts, which contributed to an increased cytoplasmic Na+ concentration. And GhBASS5-overexpressed transgenic plants showed an increase in Na+ translocation from roots to shoots and an elevated Na+ content in both roots and shoots, but a dramatic decrease in the Na+ efflux from root tissues and the K+/Na+ ratio, especially under salt stress conditions. Furthermore, overexpressing GhBASS5 greatly damaged plastid functions and enhanced salt sensitivity in transgenic Arabidopsis when compared with wild-type plants under salt stress. Additionally, the salt-responsive transporter genes that regulate K+/Na+ homeostasis were dramatically expressed in GhBASS5-overexpressed lines, especially under salt stress conditions. Taken together, our results suggest that GhBASS5 is a plastid-localized Na+ transporter, and high expression of GhBASS5 impairs salt tolerance of plants via increasing Na+ transportation and accumulation at both cell and tissue levels.

The cotton endocycle-involved protein SPO11-3 functions in salt stress via integrating leaf stomatal response, ROS scavenging and root growth.

The SPORULATION 11 (SPO11) proteins are among eukaryotic the topoisomerase VIA (Topo VIA) homologs involved in modulating various important biological processes, such as growth, development and stress response via endoreduplication in plants, but the underlying mechanism response to stress remains largely unknown under salt treatment. Here, we attempted to characterize a homolog of TOP VIA in upland cotton (Gossypium hirsutum L.), designated as GhSPO11-3. The silencing of GhSPO11-3 in cotton plants resulted in a dwarf phenotype with a failure of cell endoreduplication and a phase shift in the ploidy levels. The GhSPO11-3-silenced plants also showed substantial changes including accumulated malondialdehyde, significantly reduced chlorophyll and proline contents and decreased antioxidative enzyme activity after salt treatment. In addition, transgenic Arabidopsis lines overexpressing GhSPO11-3 accelerated both leaf and root growth with cell expansion and endopolyploidy. Both leaf stomatal density and aperture were markedly decreased, and the transgenic Arabidopsis lines were more tolerant with expression of stress-responsive genes under salinity stress. Furthermore, consistent with the reduced reactive oxygen species (ROS), the expression of ROS scavenging-related genes was largely reinforced, and antioxidant enzyme activities were accordingly significantly enhanced in transgenic Arabidopsis lines under salt stress. In general, these results indicated that GhSPO11-3 likely respond to salt stress by positively regulating root growth, stomatal response, ROS production and the expression of stress-related genes to cope with adverse conditions in plants.

Helminth protection against autoimmune diabetes in nonobese diabetic mice is independent of a type 2 immune shift and requires TGF-ß.

Leading hypotheses to explain helminth-mediated protection against autoimmunity postulate that type 2 or regulatory immune responses induced by helminth infections in the host limit pathogenic Th1-driven autoimmune responses. We tested these hypotheses by investigating whether infection with the filarial nematode Litomosoides sigmodontis prevents diabetes onset in IL-4-deficient NOD mice and whether depletion or absence of regulatory T cells, IL-10, or TGF-ß alters helminth-mediated protection. In contrast to IL-4-competent NOD mice, IL-4-deficient NOD mice failed to develop a type 2 shift in either cytokine or Ab production during L. sigmodontis infection. Despite the absence of a type 2 immune shift, infection of IL-4-deficient NOD mice with L. sigmodontis prevented diabetes onset in all mice studied. Infections in immunocompetent and IL-4-deficient NOD mice were accompanied by increases in CD4(+)CD25(+)Foxp3(+) regulatory T cell frequencies and numbers, respectively, and helminth infection increased the proliferation of CD4(+)Foxp3(+) cells. However, depletion of CD25(+) cells in NOD mice or Foxp3(+) T cells from splenocytes transferred into NOD.scid mice did not decrease helminth-mediated protection against diabetes onset. Continuous depletion of the anti-inflammatory cytokine TGF-ß, but not blockade of IL-10 signaling, prevented the beneficial effect of helminth infection on diabetes. Changes in Th17 responses did not seem to play an important role in helminth-mediated protection against autoimmunity, because helminth infection was not associated with a decreased Th17 immune response. This study demonstrates that L. sigmodontis-mediated protection against diabetes in NOD mice is not dependent on the induction of a type 2 immune shift but does require TGF-ß.

Diabetes Distress Among Patients Undergoing Surgery for Diabetic Retinopathy and Associated Factors: A Cross-Sectional Survey.

Background: Diabetes distress (DD) is a negative emotion related to diabetes management and a predictor of depression; it affects diabetic retinopathy (DR) patients' quality of life and disease outcomes. The prevalence of DD was higher in patients undergoing surgery for DR. However, few studies have been conducted on DD in DR surgery patients. The present study aims to investigate the status of DD in DR surgery patients and identify factors associated with DD. Methods: Using a convenience sampling method, 210 DR surgery patients who were admitted to 2 tertiary-level hospitals in Wenzhou City (Zhejiang Province) and Zhengzhou City (Henan Province) from February to June 2023 were selected as research subjects. A questionnaire collecting demographic and disease-related information, the Diabetes Distress Scale, the Summary of Diabetes Self-Management Activities, the Family Care Index Scale, and the Social Support Rating Scale were used to collect data. Statistical analyses included descriptive statistics, t tests, ANOVAs, Pearson's correlation analyses and stepwise multiple linear regression. This study is reported according to the STROBE guidelines. Results: In total, 156 out of 210 (74.29%) DR surgery patients experienced DD, with an average score of 2.13±0.63. The results of the stepwise multiple regression analysis showed that residential location, employment status, self-management level, family support, and social support were significantly associated with DD. These variables accounted for 30.6% of the total variation in DD. Conclusions: DR surgery patients exhibit moderate levels of distress. Health care professionals should pay attention to DD in DR surgery patients and develop targeted interventions to improve the self-management ability of these patients, increase their family support and social support to reduce their DD levels.

Intraoperative Intraocular Lens Waste: Incidence, Cost and Reasons.

PURPOSE: To evaluate the incidence and cost of intraocular lens(IOL) waste during IOL implantation, as well as the reasons for it. METHODS: A retrospective analysis was conducted on the data of 485 patients from the IOL waste registers of a single tertiary eye hospital in China during 2016-2020. The primary outcomes were the incidence, cost, and reasons for different IOL properties. Cases were examined to ascertain IOL material, design, procedural details, and causes of waste. RESULTS: IOL waste occurred in 485 (6.62‰) of the 73,246 IOL implantations during the study period. The total cost of IOL waste was 429, 850.26 Chinese Yuan (CNY) related to waste with an average cost of 2, 442.33 CNY per procedure during the study period. Comparisons between IOL properties showed that polymethyl methacrylate (PMMA) material (39, 2.05%), three-piece design (142, 1.49%), and secondary IOL implantation (26, 2.16%) were associated with IOL wastage, and the difference was statistically significant. The causes of IOL waste were damage (107, 60.80%), patient reasons (37, 21.26%), aseptic errors (22, 12.50%), IOL quality problems (8, 4.55%), and loss (2, 1.14%). CONCLUSIONS: The incidence of IOL waste is low, but still leads to a significant cost burden due to a large number of cataract surgeries. PMMA material, three-piece design, and secondary implantation were identified as factors increasing IOL waste. Damage emerged as the primary reason for waste, largely attributed to human error. Therefore, the development of strategies to mitigate IOL waste is imperative.

Vaccination with intestinal tract antigens does not induce protective immunity in a permissive model of filariasis.

Antigens obtained from the intestinal tract of filarial nematodes have been proposed as potential safe and effective vaccine candidates. Because they may be 'hidden' from the immune response during natural infection, yet accessible by antibodies induced by vaccination, intestinal antigens may have a low potential for eliciting allergic responses when vaccinating previously infected individuals. Despite prior promising data, vaccination with intestinal antigens has yet to be tested in a permissive model of filariasis. In this study we investigated the efficacy of vaccination with filarial intestinal antigens in the permissive Litomosoides sigmodontis BALB/c model of filariasis, and we evaluated the extent to which these antigens are recognized by the immune system during and after infection. Infected BALB/c mice developed lower IgG antibody responses to soluble intestinal antigens (GutAg) than to soluble antigens of whole worms (LsAg). Similarly, GutAg induced less proliferation and less production of IL-4 and IFNγ from splenocytes of infected mice than LsAg. In contrast to these differences, active infection resulted in equivalent levels of circulating GutAg-specific IgE and LsAg-specific IgE levels. Consistent with this, basophil activation, as assessed by flow cytometric staining of intracellular basophil IL-4 expression, was equivalent in response to GutAg and LsAg. Vaccination with GutAg adsorbed to CpG/alum induced GutAg specific IgG1 and IgG2A production, with GutAg specific IgG titers greater than 5-fold higher than those measured in previously infected animals. Despite this response to GutAg vaccination, vaccinated mice harbored similar parasite burdens 8 weeks post infection when compared to non-vaccinated controls. These studies demonstrate that soluble antigens obtained from the intestinal tracts of L. sigmodontis have some qualities of 'hidden' antigens, but they still sensitize mice to allergic reactions and fail to protect against future infection when given as a vaccine adsorbed to alum/CPG.

Abdominal Massage Ameliorates Inguinal Fat Accumulation via Augmentation of PPARγ Signaling in High-Fat Diet-Induced Obese Mice.

Purpose: With the increase in prevalence and decrease in age of the obese population, safer weight loss methods have attracted growing attention. While abdominal massage (AM) has been clinically proven for weight loss, the mechanism thereof has yet to be elucidated. We aimed to investigate the effect of AM on abdominal fat in obese mice fed a high-fat diet and explore the possible mechanisms involved. Materials and Methods: Male C57BL/6J mice were fed a high-fat diet for 16 weeks and then treated with AM for 5 weeks; mice fed a standard diet were used as normal controls. Blood and adipose tissue, including inguinal white adipose tissue (WAT) and epididymal WAT, were collected from the mice after the intervention. We explored the mechanism of weight reduction through inguinal WAT transcriptome sequencing, quantitative real-time polymerase chain reaction (PCR) validation, and Western blot. Results: The results revealed that AM decreased fat mass, weight, glucose, and serum lipid levels. Meanwhile, AM enhanced the expression of the peroxisome proliferator-activated receptor gamma (PPARγ) and other downstream genes (Fabp4, Acox3, Pck1, and Aqp7) in inguinal WAT. In addition, AM increased the expression of PPARγ protein. Conclusion: AM may promote fatty acid oxidation, lipid metabolism, and glucose homeostasis by activating the PPARγ signaling pathway in inguinal WAT, thereby exhibiting therapeutic efficacy against obesity, even in the presence of a persistent high-fat diet.

Expression of FMD virus-like particles in yeast Hansenula polymorpha and immunogenicity of combine with CpG and aluminum adjuvant.

BACKGROUND: Inactivated vaccines are limited in preventing foot-and-mouth disease (FMD) due to safety problems. Recombinant virus-like particles (VLPs) are an excellent candidate for a novel vaccine for preventing FMD, given that VLPs have similar immunogenicity as natural viruses and are replication- and infection-incompetent. OBJECTIVES: The 3C protease and P1 polyprotein of type O FMD virus (FDMV) was expressed in yeast Hansenula polymorpha to generate self-resembling VLPs, and the potential of recombinant VLPs as an FMD vaccine was evaluated. METHODS: BALB/c mice were immunized with recombinant purified VLPs using CpG oligodeoxynucleotide and aluminum hydroxide gel as an adjuvant. Cytokines and lymphocytes from serum and spleen were analyzed by enzyme-linked immunosorbent assay, enzyme-linked immunospot assay, and flow cytometry. RESULTS: The VLPs of FMD were purified successfully from yeast protein with a diameter of approximately 25 nm. The immunization of mice showed that animals produced high levels of FMDV antibodies and a higher level of antibodies for a longer time. In addition, higher levels of interferon-γ and CD4+ T cells were observed in mice immunized with VLPs. CONCLUSIONS: The expression of VLPs of FMD in H. polymorpha provides a novel strategy for the generation of the FMDV vaccine.

A discussion of RNA virus taxonomy based on the 2020 International Committee on Taxonomy of Viruses report.

RNA viruses have a higher mutation rate than DNA viruses; however, RNA viruses are insufficiently studied outside disease settings. The International Committee on Taxonomy of Viruses (ICTV) is an organization set up by virologists to standardize virus classification. To better understand ICTV taxonomy and the characteristics and rules of different RNA virus families, we analyzed the 3,529 RNA viruses included in the 2020 ICTV report using five widely used metrics: length, host, GC content, number of predicted ORFs, and sequence similarity. The results show that host type has a significant influence on viral genome length and GC content. The genome lengths of virus members within the same genus are quite similar: 98.28% of the genome length differences within any particular genus are less than 20%. The species within those genera containing segmented viruses also have a similar length and number of segments. The number of predicted ORFs in the RNA viral genomes also shows a strong, statistically significant correlation with genome length. We suggest that due to the high mutation rate of RNA virus genomes, current RNA virus classification should mainly rely on protein similarities rather than nucleic acid similarities.

Anti-FcεR1 antibody injections activate basophils and mast cells and delay Type 1 diabetes onset in NOD mice.

Mounting evidence suggests that helminth infections protect against autoimmune diseases. As helminths cause chronic IgE-mediated activation of basophils and mast cells we hypothesized that continuous activation of these cells could prevent diabetes onset in nonobese diabetic (NOD) mice in the absence of infection. Anti-FcεR1 activated basophils and mast cells and resulted in the release of IL-4 and histamine into the bloodstream. Anti-FcεR1-treated NOD mice showed a type 2 shift in insulin-specific antibody production and exhibited significant delays in diabetes onset. IL-4 responses played a partial role as the protective effect of anti-FcεR1 therapy was diminished in IL-4-deficient NOD mice. In contrast, histamine signaling was not required as anti-FcεR1-mediated protection was not reduced in mice treated with histamine receptor blockers. These results demonstrate that anti-FcεR1 therapy delays diabetes onset in NOD mice and suggest that chronic basophil and mast cell activation may represent a new avenue of therapy for Th1-associated autoimmune diseases.

Telmisartan attenuates isoproterenol-induced cardiac remodeling in rats via regulation of cardiac adiponectin expression.

AIM: To investigate whether telmisartan (Telm) pretreatment attenuates isoproterenol (Iso)-induced postinfarction remodeling (PIR) in rats, and whether the effect of Telm is associated with cardiac expression of adiponectin. METHODS: PIR was induced in male Wistar rats with two consecutive injections of Iso (80 mg/kg, sc) at an interval of 24 h. Primary culture of ventricular myocytes from neonatal rats was prepared. Iso-induced cardiomyocyte injury was assessed based on cell growth and lactate dehydrogenase (LDH) activity. Cardiac adiponectin expression was measured using qRT-PCR and immunoblot analysis. RESULTS: In the rats with PIR, Telm (10 mg·kg(-1)·d(-1), po for 65 d) suppressed Iso-induced increases in gravimetric parameters, cardiomyocyte diameter and collagen volume fraction, but had no effect on Iso-induced myocardial hypertrophy and interstitial fibrosis. The protective effect of Telm was associated with enhanced protein expression of cardiac adiponectin. In cultured cardiomyocytes, Telm (5-20 µmol/L) inhibited the cell death and LDH release induced by Iso (10 µmol/L), and reversed Iso-induced reduction in adiponectin protein expression. In cardiomyocytes exposed to Iso (20 µmol/L), GW9662 (30 µmol/L), a selective antagonist of PPAR-γ, blocked the effects of Telm pretreatment on adiponectin protein expression, as well as the protective effects of Telm on Iso-induced cell injury. CONCLUSION: Telm attenuates Iso-induced cardiac remodeling and cell injury, which is associated with induction of cardiac adiponectin expression.

[Changes of ocular higher order aberration in keratoconus eyes wearing rigid gas-permeable contact lens].

OBJECTIVE: To compare the wavefront characteristics of normal and keratoconus eyes with and without rigid gas-permeable contact lens (RGPCL), and to evaluate the visual quality in keratoconus eyes corrected by RGPCL. METHODS: Retrospective study. Higher order aberrations (HOAs) of 90 eyes in 56 keratoconus patients and 30 eyes of 17 subjects with refractive errors were quantified with a Bausch&Lomb Zywave Wavefront Analyzer. The keratoconus eyes were divided into mild (28 eyes), moderate (33 eyes) and severe (29 eyes) groups. Zernike's polynomial was used to describe the wavefront measurements. Root mean square (RMS) values of the total HOAs, S3, S4, S5, total coma (T. Coma) and total spherical aberrations (T. Sph) were obtained in the same eye with and without contact lenses. We used paired sample t-test and independent-samples t-test to analyze the data. RESULTS: Mean RMS values for High (F = 72.12, P(1) = 0.00), S3 (F = 68.15, P = 0.00), S4 (F = 24.95, P(1) = 0.00), T. Coma (F = 44.67, P = 0.00), T. Sph (F = 28.90, P = 0.01) increased significantly from mild to sever keratoconus eyes RMS values of the total HOAs (t = 4.83), S3 (t = 4.39), total coma (t = 3.71) of refractive error eyes decreased significantly after fitting with RGPCL (P < 0.05). RMS values of the total HOAs (t = 8.27), S3 (t = 8.14), S4 (t = 2.29), total coma (t = 4.38) of mild keratoconus eyes decreased significantly after fitting with RGPCL (P < 0.05) RMS values of the total HOAs (t = 8.03), S3 (t = 7.22), s4 (t = 4.38), S5 (t = 4.53), total coma (t = 5.26) and total spherical (t = 2.77) of moderate keratoconus eyes decreased significantly after fitting with RGPCL (P < 0.05). Every high front-wave aberration of mild keratoconus eyes decreased to refractive error eyes'level after RGPCL fitting. Moderate (t(HOAs) = 0.63, t(s3) = 0.31, t(s4) = 1.70, t(s5) = 0.95, t(coma) = 0.06, t(spherical) = 1.99) and sever keratoconus eyes' higher order aberrations decreased significantly after RGPCL fitting (t(HOAs) = 7.50, t(s3) = 5.25, t(s4) = 5.50, t(s5) = 3.02, t(coma) = 5.90, t(spherical) = 4.60), but they still degrade compared with refractive error eyes (P < 0.05). CONCLUSIONS: RGPCL could reduce high aberrations and improve optical quality in keratoconus eyes. But the visual performance in moderate and severe keratoconus eyes with a RGPCLs is still poorer than that of normal eyes even if the corrected visual acuity is good.