Targeting pathogenic CD8+ tissue-resident T cells with chimeric antigen receptor therapy in murine autoimmune cholangitis.

Primary biliary cholangitis (PBC) is a cholestatic autoimmune liver disease characterized by autoreactive T cell response against intrahepatic small bile ducts. Here, we use Il12b-/-Il2ra-/- mice (DKO mice) as a model of autoimmune cholangitis and demonstrate that Cd8a knockout or treatment with an anti-CD8α antibody prevents/reduces biliary immunopathology. Using single-cell RNA sequencing analysis, we identified CD8+ tissue-resident memory T (Trm) cells in the livers of DKO mice, which highly express activation- and cytotoxicity-associated markers and induce apoptosis of bile duct epithelial cells. Liver CD8+ Trm cells also upregulate the expression of several immune checkpoint molecules, including PD-1. We describe the development of a chimeric antigen receptor to target PD-1-expressing CD8+ Trm cells. Treatment of DKO mice with PD-1-targeting CAR-T cells selectively depleted liver CD8+ Trm cells and alleviated autoimmune cholangitis. Our work highlights the pathogenic role of CD8+ Trm cells and the potential therapeutic usage of PD-1-targeting CAR-T cells.

SGLT2i relieve proteinuria in diabetic nephropathy patients potentially by inhibiting renal oxidative stress rather than through AGEs pathway.

AIMS: To estimate the effects of the sodium-glucose cotransporter 2 inhibitor (SGLT2i) on proteinuria and oxidative stress expression in type 2 diabetes patients. MATERIALS AND METHODS: 68 patients with type 2 diabetes mellitus (T2DM) were divided into three groups according urinary albumin-to-creatinine ratio (UACR), including T2DM with non-albuminuria group (UACR < 30 mg/g), T2DM with microalbuminuria group (30 ≤ UACR ≤ 300 mg/g), T2DM with macroalbuminuria group (UACR>300 mg/g). They all received SGLT2 inhibitors (SGLT2i) treatment for 12 weeks. The expression of advanced glycation end products (AGEs) in plasma and 8-hydroxy-2-deoxyguanosine (8-OHdG) in urine were measured as indications of oxidative stress. The 24-hour urine samples were collected to measure the concentration of proteinuria and 8-OHdG before and after 12 weeks SGLT2i treatment. Plasma renin activity (PRA), angiotensin II (Ang II) and Aldosterone (ALD) were measured to evaluate renin angiotensin aldosterone system (RASS) levels. RESULTS: After 12 weeks SGLT2 inhibitors treatment, the median values of 24-hour proteinuria decreased in macroalbuminuria compared to baseline (970 vs. 821 mg/d, P = 0.006). The median values of AGEs and 8-OHdG decreased in microalbuminuria and macroalbuminuria groups when compared to baseline, AGEs (777 vs. 136 ug/ml, P = 0.003) and (755 vs. 210 ug/ml, P = 0.001), 8-OHdG (8.00 vs. 1.88 ng/ml, P = 0.001) and (11.18 vs. 1.90 ng/ml, P < 0.001), respectively. Partial correlations showed that 8-OHdG were relevant to the baseline 24-h proteinuria (r = 0.389, p = 0.001), the reduction of OHdG (Δ8-OHdG) were positively correlated with the decrease of 24-h proteinuria (Δ24-h proteinuria) after 12 weeks of SGLT2i treatment (r = 0.283, P = 0.031). There was no significant correlation between 24-h proteinuria and AGEs in baseline (r = -0.059, p = 0.640) as well as between ΔAGEs and Δ24-h proteinuria (r = 0.022, p = 0.872) after12 weeks of SGLT2i treatment in T2DM patients. CONCLUSIONS: SGLT2i may reduce proteinuria in diabetic nephropathy patients, potentially by inhibiting renal oxidative stress, but not through the AGEs pathway and does not induce RAAS activation. TRIAL REGISTRATION: This clinical trial was registered on 15/10/2019, in ClinicalTrials.gov, and the registry number is NCT04127084.

Analysis of Hot Tensile Fracture and Flow Behaviors of Inconel 625 Superalloy.

In this work, Inconel 625 alloy is explored regarding high-temperature tensile deformation and fracture behaviors at a strain rate of 0.005-0.01 s-1 under a deformation temperature ranging from 700-800 °C. The subsequent analysis focuses on the impact of deformation parameters on flow and fracture characteristics. The fractured surface reveals that ductile fracture is dominated by the nucleation, growth, and coalescence of microvoids as the primary failure mechanisms. The elevated deformation temperature and reduced strain rate stimulate the level of dynamically recrystallized (DRX) structures, resulting in intergranular fractures. The Arrhenius model and the particle swarm optimization-artificial neural network (PSO-ANN) model are developed to predict the hot tensile behavior of the superalloy. It indicates that the PSO-ANN model exhibits a correlation coefficient (R) as high as 0.9967, surpassing the corresponding coefficient of 0.9344 for the Arrhenius model. Furthermore, the relative absolute error of 9.13% (Arrhenius) and 1.85% (PSO-ANN model) are recorded. The developed PSO-ANN model accurately characterizes the flow features of the Inconel 625 superalloy with high precision and reliability.

Identification of Key Genes and Related Drugs of Adrenocortical Carcinoma by Integrated Bioinformatics Analysis.

Adrenocortical carcinoma (ACC) is a malignant carcinoma with an extremely poor prognosis, and its pathogenesis remains to be understood to date, necessitating further investigation. This study aims to discover biomarkers and potential therapeutic agents for ACC through bioinformatics, enhancing clinical diagnosis and treatment strategies. Differentially expressed genes (DEGs) between ACC and normal adrenal cortex were screened out from the GSE19750 and GSE90713 datasets available in the GEO database. An online Venn diagram tool was utilized to identify the common DEGs between the two datasets. The identified DEGs were subjected to functional assessment, pathway enrichment, and identification of hub genes by performing the protein-protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The differences in the expressions of hub genes between ACC and normal adrenal cortex were validated at the GEPIA2 website, and the association of these genes with the overall patient survival was also assessed. Finally, on the QuartataWeb website, drugs related to the identified hub genes were determined. A total of 114 DEGs, 10 hub genes, and 69 known drugs that could interact with these genes were identified. The GO and KEGG analyses revealed a close association of the identified DEGs with cellular signal transduction. The 10 hub genes identified were overexpressed in ACC, in addition to being significantly associated with adverse prognosis in ACC. Three genes and the associated known drugs were identified as potential targets for ACC treatment.

Organic Integration of Traditional Chinese and Western Medicines-Future of Clinical Practice Guidelines of Integrated Traditional Chinese and Western Medicines.

The transformation and implementation of clinical practice guidelines for integrated traditional Chinese medicine (TCM) and Western medicine (WM) is crucial to the adoption of medical science and technological findings and is an important way for TCM to be made available to the world. First, clinical practice guidelines (CPGs) of TCM and WM integration in recent years was analyzed to clarify the current situation and problems in the existing guidelines according to the following four perspectives: (1) perspective of TCM and WM integration in guidelines, (2) diagnosis Using integrated TCM and WM, (3) integration of TCM and WM treatment, (4) promoting TCM and WM integration. Secondly, the information and quality evaluation of CPGs for integrated Chinese and Western medicine in 2020-2022 were analyzed to explore the degree and methods of integration of Chinese and Western medicine guidelines. And last this study aimed to lay a foundation for the further establishment of Chinese characteristic, repeatable, and calculable clinical practice guidelines of TCM and WM integration.

Traditional Chinese Manual Therapy (Tuina) reshape the function of default mode network in patients with lumbar disc herniation.

Purpose: Investigating the changes of regional homogeneity (ReHo) values and both static and dynamic functional connectivity (FC) before and after Traditional Chinese Manual Therapy (Tuina) in patients with lumbar disk herniation (LDH) through resting-state functional magnetic resonance imaging (RS-fMRI). Based on this, we observe the effect of Tuina on the above abnormal changes. Methods: Patients with LDH (n = 27) and healthy controls (HCs) (n = 28) were recruited. The functional magnetic resonance imaging (fMRI) scanning was performed two times in LDH patients, before Tuina (time point 1, LDH-pre) and after the sixth Tuina (time point 2, LDH-pos). And for one time in HCs which received no intervention. The ReHo values were compared between LDH-pre and HCs. The significant clusters detected by ReHo analysis were selected as seeds to calculate static functional connectivity (sFC). We also applied the sliding-window to perform dynamic functional connectivity (dFC). To evaluate the Tuina effect, the mean ReHo and FC values (both static and dynamic) were extracted from significant clusters and compared between LDH and HCs. Results: In comparison to HCs, LDH patients displayed decreased ReHo in the left orbital part middle frontal gyrus (LO-MFG). For sFC analysis, no significant difference was found. However, we found decreased dFC variance between LO-MFG and the left Fusiform, and increased dFC variance in the left orbital inferior frontal gyrus and left precuneus. Both ReHo and dFC values revealed after Tuina, the brain activities in LDH patients were similar to HCs. Conclusion: The present study characterized the altered patterns of regional homogeneity in spontaneous brain activity and those of functional connectivity in patients with LDH. Tuina can reshape the function of the default mode network (DMN) in LDH patients, which may contribute to the analgesic effect of Tuina in LDH patients.

Thioparib inhibits homologous recombination repair, activates the type I IFN response, and overcomes olaparib resistance.

Poly-ADP-ribose polymerase (PARP) inhibitors (PARPi) have shown great promise for treating BRCA-deficient tumors. However, over 40% of BRCA-deficient patients fail to respond to PARPi. Here, we report that thioparib, a next-generation PARPi with high affinity against multiple PARPs, including PARP1, PARP2, and PARP7, displays high antitumor activities against PARPi-sensitive and -resistant cells with homologous recombination (HR) deficiency both in vitro and in vivo. Thioparib treatment elicited PARP1-dependent DNA damage and replication stress, causing S-phase arrest and apoptosis. Conversely, thioparib strongly inhibited HR-mediated DNA repair while increasing RAD51 foci formation. Notably, the on-target inhibition of PARP7 by thioparib-activated STING/TBK1-dependent phosphorylation of STAT1, triggered a strong induction of type I interferons (IFNs), and resulted in tumor growth retardation in an immunocompetent mouse model. However, the inhibitory effect of thioparib on tumor growth was more pronounced in PARP1 knockout mice, suggesting that a specific PARP7 inhibitor, rather than a pan inhibitor such as thioparib, would be more relevant for clinical applications. Finally, genome-scale CRISPR screening identified PARP1 and MCRS1 as genes capable of modulating thioparib sensitivity. Taken together, thioparib, a next-generation PARPi acting on both DNA damage response and antitumor immunity, serves as a therapeutic potential for treating hyperactive HR tumors, including those resistant to earlier-generation PARPi.

Herpes simplex keratitis following Smart Pulse Technology assisted transepithelial photorefractive keratectomy: a case report.

BACKGROUND: Herpes simplex keratitis (HSK) is a rare and sight-threatening complication following refractive surgery. SmartSurfACE surgery is the result of combining transepithelial photorefractive keratectomy (trans-PRK) with Smart Pulse Technology (SPT) to diminish surface irregularities of the residual stromal bed after surgery with less pain, faster re-epithelialization, and better postoperative visual acuity. In this article, we report the first case of HSK following SmartSurf ACE without history of herpetic eye disease. CASE PRESENTATION: A 21-year-old woman underwent bilateral SmartSurfACE without history of clinical herpetic infection, active eye disease, or systemic disease. Mild superficial punctate keratitis occurred on the tenth postoperative day. The condition was not improved by ophthalmic drugs of anti-inflammation or epithelial healings. Dendritic corneal ulcer appeared within one month, which is the commonly recognized clinical manifestation of herpes simplex keratitis. The patient was managed with topical and systemic antiviral agents. After nine days of antiviral therapy, the lesion healed up, remaining mild stromal scarring in both eyes ultimately. CONCLUSION: Herpes simplex keratitis is a rare but sight-threatening complication following refractive surgery. For the ocular irritation symptoms of postoperative patients, we should consider the possibility of HSK and give timely treatment.

Effectiveness of nursing interventions on the sexual quality of life of patients with breast cancer: A systematic review and meta-analysis.

BACKGROUND: Although many studies have reported the effectiveness of nursing interventions on the sexual quality of life of patients with breast cancer, the results have not been synthesized. This study aims to assess the effectiveness of nursing interventions on the sexual quality of life of patients with breast cancer. REVIEW METHODS: A comprehensive search was conducted in 11 databases from inception to October 7, 2021. Studies evaluating the effects of nursing interventions on sexual quality of life were included. Study selection, data extraction, and risk of bias assessment were performed by two independent reviewers. RESULTS: This review pooled 38 studies with 3,664 participants. Meta-analysis results showed that nursing interventions significantly improved sexual quality of life, including sexual function (standardized mean difference [SMD] = 0.98, 95% confidence interval [CI] = [0.60-1.37], P < 0.001) and sexual satisfaction (SMD = 0.99, 95% CI = [0.41-1.57], P < 0.001). In addition, depression (SMD = -1.16, 95% CI = [-2.08--0.24], P = 0.01) and general quality of life (SMD = 0.20, 95% CI = [0.08-0.33], P = 0.002) were significantly improved, but body image (SMD = 0.17, 95% CI = [-0.08-0.41], P = 0.19) and anxiety (SMD = -0.45, 95% CI = [-0.93-0.02], P = 0.06) did not significantly improve. Subgroup analysis showed that nursing interventions had a stronger long-term effect on sexual function (SMD = 1.15, 95% CI = [0.51-1.80], P = P < 0.001) and was more effective in younger patients (SMD = 1.43, 95% CI = [0.63-2.23], P = P < 0.001). Nursing interventions showed a statistically significant short-term effect on sexual satisfaction (SMD = 1.32, 95% CI = [0.44-2.20], P = 0.003) and a significant effect in older patients (SMD = 1.27, 95% CI = [0.46-2.08], P = 0.002). CONCLUSIONS: Nursing intervention may be an effective way to improve the sexual quality of life of patients with breast cancer. Nursing interventions had a stronger long-term effect on sexual function, and the group with the strongest effect is the younger patients. Nursing interventions showed a significant short-term effect on sexual satisfaction, and older patients had significant improvement in sexual satisfaction.

Three-dimensional psychological guidance combined with evidence-based health intervention in patients with liver abscess treated with ultrasound.

BACKGROUND: Liver abscess is a common clinical liver disease mainly caused by suppurative bacteria or amoebae, with early clinical signs of chills, high fever, jaundice, and other symptoms. Establishing its early diagnosis is difficult, which may lead to misdiagnosis. AIM: To observe the effects of psychological guidance combined with evidence-based health intervention in patients with liver abscess treated with ultrasound. METHODS: A total of 120 patients with bacterial liver abscess admitted to our hospital from May 2018 to February 2021 were selected and divided into groups according to their intervention plan. RESULTS: After the intervention, Self-Rating Depression Scale, Self-Rating Anxiety Scale, Self-Perceived Burden Scale (SPBS), and quality of life scores (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional, mental health) were lower than before the intervention in the two groups. The observation group had lower negative sentiment, SPBS, and quality of life scores than the control group. In the observation group, 31 and 24 patients had good and general compliance, respectively, with a compliance rate of 91.67%, which was significantly higher than that in the control group. The observation group had significantly lower total incidence of incision infection, abdominal abscess, hemorrhage, and severe abdominal pain than the control group. CONCLUSION: Three-dimensional psychological guidance combined with evidence-based health intervention in treating liver abscess can reduce patients' burden and negative emotions, improve patient compliance and quality of life, and reduce complications.

SGLT2 inhibitors attenuate nephrin loss and enhance TGF-ß1 secretion in type 2 diabetes patients with albuminuria: a randomized clinical trial.

To evaluate the effect of SGLT2 inhibitor (SGLT2i) on albuminuria, nephrin (NPH) and transforming-growth-factor-beta1 (TGF-ß1) levels in urine and low-grade inflammation in type 2 diabetes (T2D) patients. A randomized, blank-controlled clinical trial included 68 T2D patients and 10 controls. Based on the urinary albumin-to-creatinine ratio (UACR), 68 diabetic patients were stratified into three levels, UACR < 30 mg/g, UACR ≧ 30 mg/g to ≦ 300 mg/g and UACR ˃ 300 mg/g, who were randomized (1:1:1) to receive SGLT2i treatment for 12 weeks. The concentrations of NPH and TGF-ß1 in urine were measured as indications of podocyte injury and renal fibrosis. Low-grade inflammation was assessed by the levels of IL-6, TNFα and hsCRP. After 12 weeks of SGLT2i treatment, the levels of UACR and NPH decreased, UTGF-ß1 increased in the T2D with microalbuminuria and macroalbuminuria groups, NPH (1.12 [0.59, 1.29] vs. 0.71 [0.41, 1.07] µg/ml, P = 0.022) and (1.29 [0.99, 1.96] vs. 0.93 [0.57, 1.31] µg/ml, P = 0.002), UTGF-ß1 (4.88 ± 1.31 vs. 7.27 ± 1.21 pg/ml, P  < 0.001) and (4.30 ± 1.34 vs. 6.78 ± 2.59 pg/ml, P  < 0.001), respectively. The changes in NPH were positively correlated with the UACR and negatively correlated with UTGF-ß1 in T2D with albuminuria. SGLT2i alleviate nephrin loss and enhance TGF-ß1 excretion in urine in T2DM with albuminuria. The anti-albuminuric effect of SGLT2i could be attributed to mitigating podocyte apoptosis and attenuating renal fibrosis.Trial registration This clinical trial was registered on 15/10/2019, in ClinicalTrials.gov, and the registry number is NCT04127084.

A spinal manipulative therapy altered brain activity in patients with lumbar disc herniation: A resting-state functional magnetic resonance imaging study.

Purpose: Lumbar disc herniation (LDH) is one of the leading causes of low-back pain and results in a series of clinical symptoms, including pain, reflex loss, and muscle weakness. Spinal manipulative therapy (SMT) can relieve pain and promote internal and external stabilization of the lumbar spine. In this study, we investigated whether the brain alterations of LDH patients with SMT were frequency-dependent based on the calculation of Amplitude of Low-Frequency Fluctuations (ALFF) and fractional ALFF (fALFF). Further, we established a cohort of LDH patients to evaluate the contribution of SMT treatments to brain functional reorganization. Methods: A total of 55 participants, including 27 LDH patients and 28 health controls (HCs), were collected. All LDH patients underwent two fMRI scans (before SMT and after the sixth SMT session). To represent LDH-related brain oscillatory activities, we calculated the ALFF and fALFF in the conventional band (0.01-0.08 Hz), the slow-4 band (0.027-0.073 Hz), and the slow-5 band (0.01-0.027 Hz). Moreover, we extracted ALFF and fALFF values in clusters with significant differences to evaluate the SMT effect. Results: Compared with HCs, the LDH patients before SMT (LDH-pre) exhibited increased fALFF in right lingual gyri in the conventional band, and showed increased fALFF in left Cerebelum_Crus1 in the slow-4 band. We further examined the abnormal brain activities changes before and after the SMT intervention. The ALFF and fALFF values of LDH-pre group were higher than those of the HCs and LDH-pos groups. After SMT, the increased ALFF and fALFF values were suppressed for patients in conventional band and slow-4 band. Conclusion: The present study characterized the altered regional patterns in spontaneous neural activity in patients with LDH. Meanwhile, SMT is an effective treatment of LDH, and we supposed that it might have been involved in modulating dysfunctional brain regions which are important for the processing of pain. The findings of the current study may provide new insights to understand pathological mechanism of LDH.

Research progress of the correlation between genotype and phenotype in hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant genetic disease characterized by left ventricular hypertrophy with prevalence of 1/500-1/200. Up to now, 1500 mutations in more than 30 genes have been found to be related to the disease. Pathogenic gene mutations together with polymorphisms of modifying genes and environmental factors play various roles in the disease processes, resulting in phenotypic heterogeneity of the disease, ranging from no symptoms to sudden cardiac death. The pathological phenotypes of HCM mainly include cardiomyocyte hypertrophy, disordered array, fibrosis, myocardial ischemia, and others. In recent years, many research efforts have been devoted to exploring the influence of HCM genotype on phenotype, and development of treatment methods based on genetics. This article focuses on the correction between HCM genotype and phenotype and summarizes the research progresses on HCM in terms of pathogenic genes, pathogenesis, associated modification factors and treatment methods, thereby providing insights on the future research and development on the genetics of HCM.

[Cognitive investigation and analysis of space loss in children].

PURPOSE: To investigate the difference of parent's cognition of children's space loss and its influencing factors, to provide reference for children's oral health education, in order to reduce the incidence of malocclusion. METHODS: A self-designed questionnaire was used to investigate the basic information and related problems of 36 parents whose children received space loss treatment. SPSS 22.0 software package was used for statistical analysis. RESULTS: Parents paid more attention to the common oral problems of their children, the awareness of oral prevention and health care were weak, the attention to treatment was higher than that of prevention. The attitude of parents to the cognition and targeted treatment of malocclusion caused by space loss was low(27.78%), which was significantly different from that of caries (75.00%) and premature loss of deciduous teeth (63.89%). The total cognition of space loss was 61.11%. The cognitive degree of parents with different characteristics was different: the cognitive degree of parents over 50 years old was lower(14.29%), the cognitive degree of parents with higher education was higher(82.35%), there was no significant difference in cognitive degree among different gender, occupation and family monthly income groups. Parents paid more attention to the basic oral health of their children, most of the interval time between this visit and the last visit was 3 months(63.89%). The main purpose of the visit was caries or tooth pain caused by caries(63.89%). Most of parents did not know the harmful effect of space loss(72.22%). There were more parents who did not know the necessity of treatment to space loss(58.33%). Parents mainly learned the treatment to space loss through the doctor's education during dental visits(72.22%). The number of active visits were less when space loss occured(22.22%), and most of parents were recommended by dentist when they came to the clinics(72.22%). Most parents were able to accept the dentists' advice on the treatment of space loss(77.78%). CONCLUSIONS: It is necessary to strengthen the propaganda, coverage and depth of oral health education care, strengthen the awareness of oral preventive health care, especially for the parents with special personality on the importance of space loss, to prevent primary teeth caries and premature loss of primary teeth, avoid the loss of dental space, make the complete primary dentition to form a normal permanent dentition.

Validity of Chinese Version of Attitudes Toward Interprofessional Health Care Teams Scale.

OBJECTIVE: Effective teamwork can provide safe and effective care in various medical systems. Thus, there is increasing recognition of the value of interprofessional collaborative practice. The Attitudes Toward Interprofessional Health Care Teams Scale (ATIHCTS) has been applied to a wide variety of health professions for evaluating attitudes toward health care teams. The ATIHCTS has been widely used internationally, but no Chinese version has been developed. The aim of this study was to adapt a Chinese version of the ATIHCTS among Chinese health care professionals and to test its validity. METHODS: The English version of the ATIHCTS was translated into Chinese, back-translated, and modified for cultural adaptation according to Brislin's guideline. A total of 306 health professionals in a Shanghai tertiary hospital were investigated using the Chinese version of the ATIHCTS to test its validity. RESULTS: The Chinese version of the ATIHCTS was adjusted based on expert review and pilot testing. According to expert opinions, the text that did not conform to the Chinese language habits and the Chinese medical environment was adjusted. A total of five adjustments were made. After the pilot testing, minor corrections were made to improve the sentence structure of the scale instructions to make it easier to understand. Factor analysis was subsequently conducted with 306 respondents. The Chinese version of the ATIHCTS had 14 items. Exploratory factor analysis extracted two common factors, quality of care and time constraints, with the cumulative variance contribution rate reaching 70.011% and the load value of each entry on its common factor > 0.4. In addition, for scale confirmatory factor analysis (CFA), the chi-square/degrees of freedom ratio (X2/df) was 1.46, the normed fit index (NFI) was 0.97, the Tucker-Lewis index (TLI) was 0.99, the incremental fit index (IFI) was 0.99, the comparative fit index (CFI) was 0.99, and the root mean square error of approximation (RMSEA) was 0.04. The fitting values all met the judgment criteria, and the scale had good structural validity. Cronbach's α of the Chinese version of the ATIHCTS was 0.861, and the Cronbach's α values of each factor were 0.949 and 0.838, respectively. The split-half reliability was 0.644, and the Guttman split-half coefficients of each factor were 0.904 and 0.779, respectively. CONCLUSION: The Chinese version of the ATIHCTS has good validity. It is a valuable tool for evaluating attitudes toward interprofessional health care teams among the health care professionals in China.

A Novel Rabbit Dry Eye Model Induced by a Controlled Drying System.

Purpose: To establish an environment-induced dry eye model in rabbits using a controlled drying system (CDS). Methods: Rabbits were randomly divided into two groups. The rabbits in the dry group were housed in the CDS, in which the relative humidity, airflow, and temperature were controlled at 22% ± 4%, 3 to 4 m/s, and 23°C to 25°C for 14 days. The rabbits in the control group were housed in a normal environment at the same time. A Schirmer test, fluorescein staining, and lissamine green staining were performed. On day 14, the eyeballs and lacrimal glands were processed for evaluating the corneal epithelial thickness, inflammatory cell infiltration index, goblet cell density, and expression of the MUC5AC protein and caspase-3 protein. The mRNA expression of the involved inflammatory genes was analyzed. Results: The CDS was able to maintain a dry environment, in which the tear production decreased, and the ocular surface staining increased over time in the rabbits. In the dry group, the corneal epithelium became thinner, inflammatory cells were noted, goblet cells and MUC5AC proteins decreased, and the increased levels of caspase-3 proteins and inflammatory cytokines were observed in the ocular surface tissues and lacrimal glands. Conclusions: This CDS could create a dry environment, in which the rabbits exhibited a pathological change in dry eye similar to that in humans. Translational Relevance: This model would be helpful in offering a platform to identify and test candidate therapies for environment-induced dry eye and to explore its underlying mechanisms.

Evolution of Annealing Twins in a Hot Deformed Nickel-Based Superalloy.

The hot deformation characteristics of a GH4169 superalloy are investigated at the temperature and strain rate ranges of 1193-1313 K and 0.01-1 s-1, respectively, through Gleeble-3500 simulator. The hot deformed microstructures are analyzed by optical microscopy (OM), transmission electron microscopy (TEM), and electron backscattered diffraction (EBSD) technology. The effects of deformation parameters on the features of flow curves and annealing twins are discussed in detail. It is found that the shapes of flow curves are greatly affected by the deformation temperature. Broad peaks appear at low deformation temperatures or high strain rates. In addition, the evolution of annealing twins is significantly sensitive to the deformation degree, temperature, and strain rate. The fraction of annealing twins first decreases and then rises with the added deformation degree. This is because the initial annealing twin characters disappear at the relatively small strains, while the annealing twins rapidly generate with the growth of dynamic recrystallized grains during the subsequent hot deformation. The fraction of annealing twins is relatively high when the deformation temperature is high or the strain rate is low. In addition, the important role of annealing twins on dynamic recrystallization (DRX) behaviors are elucidated. The obvious bulging at initial twin boundaries, and the coherency of annealing twin boundaries with dynamic recrystallized grain boundaries, indicates that annealing twins can motivate the DRX nucleation during the hot deformation.

Identifying Modifiable Risk Factors for Relapse in Patients With Schizophrenia in China.

BACKGROUND: Preventing relapse of schizophrenic patients is really a challenge. The present study sought to provide more explicit evidence and factors of different grades and weights by a series of step-by-step analysis through χ2 test, logistic regression analysis and decision-tree model. The results of this study may contribute to controlling relapse of schizophrenic patients. METHODS: A total of 1,487 schizophrenia patients were included who were 18-65 years of age and discharged from 10 hospitals in China from January 2009 to August 2009 and from September 2011 to February 2012 with improvements or recovery of treatment effect. We used a questionnaire to collect information about relapse and correlative factors during one year after discharge by medical record collection and telephone interview. The χ2 test and logistic regression analysis were used to identify risk factors and high-risk factors firstly, and then a decision-tree model was used to find predictive factors. RESULTS: The χ2 test found nine risk factors which were associated with relapse. Logistic regression analysis also showed four high-risk factors further (medication adherence, occupational status, ability of daily living, payment method of medical costs). At last, a decision-tree model revealed four predictors of relapse; it showed that medication adherence was the first grade and the most powerful predictor of relapse (relapse rate for adherence vs. nonadherence: 22.9 vs. 55.7%, χ2 = 116.36, p < 0.001). The second grade factor was occupational status (employment vs. unemployment: 19.7 vs. 42.7%, χ2 = 17.72, p < 0.001); the third grade factors were ability of daily living (normal vs. difficult: 28.4 vs. 54.3%, χ2 = 8.61, p = 0.010) and household income (household income ≥ 3000 RMB vs. <3000 RMB: 28.6 vs. 42.4%, χ2 = 6.30, p = 0.036). The overall positive predictive value (PPV) of the logistic regression was 0.740, and the decision-tree model was 0.726. Both models were reliable. CONCLUSIONS: For schizophrenic patients discharged from hospital, who had good medication adherence, more higher household income, be employed and normal ability of daily living, would be less likely to relapse. Decision tree provides a new path for doctors to find the schizophrenic inpatient's relapse risk and give them reasonable treatment suggestions after discharge.

[The role of DNA hydroxymethylation in the regulation of atherosclerosis].

As an epigenetic modification, DNA hydroxymethylation plays a significant role in regulating gene expression. In recent years, there has been increasing evidence that suggests abnormal changes of 5-hydroxymethylcytosine (5hmC) and ten-eleven translocation (TET) family proteins in cardiovascular diseases, indicating cardiovascular diseases are closely connected with DNA hydroxymethylation. The level of DNA hydroxymethylation is affected by some common risk factors of atherosclerosis, such as aging, gender, hypertension and smoking. It is also related to the immune and inflammatory reaction involved in the process of atherosclerosis as well as the function of endothelial cells and vascular smooth muscle cells. In this review, we summarize the mechanism and research status of DNA hydroxymethylation and TET family proteins towards atherosclerosis, aiming to provide a reference for the development, diagnosis and treatment of atherosclerosis.