Report of abnormal tail regeneration of Eremias yarkandensis (Sauria: Lacertidae) and its locomotor performance.

Caudal autotomy is a phenomenon observed in many reptile taxa, and tail loss is a pivotal functional trait for reptiles, with potentially negative implications for organism fitness due to its influence on locomotion. Some lizard species can regenerate a lost tail, which sometimes can lead to the development of more than one tail (i.e., abnormal tail regeneration) in the process. However, little is currently known about the impact of abnormal tail regeneration on locomotor performance. In this study, we document abnormal tail regeneration in Eremias yarkandensis, a reptile species native to northwestern China. Additionally, we investigated the sprint speed and endurance performance of these lizards. This study provides the first report on abnormal tail regeneration and its locomotor performance on a Chinese reptile. We suggest that the abnormal regeneration of tails may contribute to the accumulation of food reserves in the species. In light of our findings, we propose that herpetologists continue to share their sporadic observations and assess the locomotor performance of species experiencing abnormal tail regeneration, further expanding our understanding of this intriguing phenomenon.

The effect of the back optic zone diameter on the treatment zone area and axial elongation in orthokeratology.

PURPOSE: To investigate the influence of corneal parameters on the treatment zone area (TZA) after Corneal Refractive Therapy (CRT) with a 5.0-mm back optical zone diameter (BOZD) were worn and to compare changes in the axial length (AL) with traditional 6.0-mm BOZD lenses. METHODS: This retrospective study involved 146 subjects (7-12 years) who wore orthokeratology (ortho-K) lenses for one year: 86 subjects were treated with CRT 5.0-mm lenses, and 60 subjects were treated with CRT 6.0-mm lenses. The TZA was measured after one year of ortho-K treatment. Both TZA and AL elongation after wearing the two kinds of lenses was compared. The parameters were recorded in the CRT 5.0 group: flat K, steep K, corneal toricity, e value, and anterior corneal elevation values at the 3-, 4-, and 5-mm chords along the principal meridians of the superior, inferior, nasal, and temporal sides. The relationships between these data and the TZA were analyzed. RESULTS: The TZA was 12.90 ± 5.15 mm2 and 20.61 ± 4.54 mm2, and the AL elongation was 0.15 ± 0.18 mm and 0.26 ± 0.18 mm in the CRT 5.0 group and the CRT 6.0 group, respectively (all p < 0.001). The one-year AL elongation was significantly associated with initial age and the TZA (r =  - 0.394, 0.393; all p < 0.001) in the CRT 5.0 group. The following corneal parameters were found to have statistically significant correlations with the TZA: the e value, difference in corneal elevation (nasal-temporal at the 3-, 4-, and 5-mm chord), and the absolute value of elevation difference (nasal-temporal at the 3- and 4-mm chord and inferior-superior at the 3-, 4-, and 5-mm chord). The e value was the only relevant factor for the TZA by multiple regression analysis (unstandardized ß = 14.219, p = 0.008). In the CRT 6.0 group, the one-year AL elongation was statistically significantly associated only with initial age (r =  - 0.605, p = 0.005), but not with the TZA (p = 0.161). CONCLUSIONS: A smaller TZA induced by a smaller BOZD may be beneficial for retarding AL elongation in children undergoing ortho-K treatment. The morphology and eccentricity of the cornea may show effects on the TZA.

Potential role of RhoA GTPase regulation in type interferon signaling in systemic lupus erythematosus.

OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by abnormal activation of the type I interferon (IFN) pathway, which results in tissue inflammation and organ damage. We explored the role of the RhoA GTPase in the type I IFN activation pathway to provide a potential basis for targeting GTPase signaling for the treatment of SLE. METHODS: Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) of SLE patients and healthy controls, and the mRNA expression levels of RhoA and IFN-stimulated genes were measured by SYBR Green quantitative reverse transcriptase-polymerase chain reaction. IFN-a-stimulated response element (ISRE)-luciferase reporter gene assays and Western blotting were conducted to assess the biologic function of RhoA. An enzyme-linked immunoassay (ELISA) measured C-X-C motif chemokine ligand 10 (CXCL10) protein expression. RESULTS: Our studies demonstrate that the expression of RhoA in the PBMCs of SLE subjects was significantly higher than in healthy controls and positively correlated with type I IFN scores and type I IFN-stimulated gene (ISGs) expression levels. SiRNA-mediated knockdown of RhoA and the RhoA/ROCK inhibitor Y27632 reduced the activity of the type I IFN-induced ISRE, the signal transducer and activator of transcription 1 (STAT-1) phosphorylation, and the expression of CXCL10 and 2'-5'-oligoadenylate synthetase 1 (OAS1). Finally, we verified that Y27632 could significantly down-regulate the OAS1 and CXCL10 expression levels in the PBMCs of SLE patients. CONCLUSION: Our study shows that RhoA positively regulates the activation of the type I IFN response pathway. Reducing the expression level of RhoA inhibits the abnormal activation of the type I IFN system, and the RhoA/ROCK inhibitor Y27632 decreases aberrant type I IFN signaling in SLE PBMCs, suggesting the possibility of targeting the RhoA GTPase for the treatment of SLE.

A small molecule macrophage migration inhibitory factor agonist ameliorates age-related myocardial intolerance to ischemia-reperfusion insults via metabolic regulation.

Macrophage migration inhibitory factor (MIF) is an innate cytokine that regulates both inflammatory and homeostatic responses. MIF is expressed by cardiomyocytes, where it exerts a protective action against ischemia-reperfusion (I/R) injury by activating AMP-activated protein kinase (AMPK). This effect is attenuated in the senescent heart due to an intrinsic, age-related reduction in MIF expression. We hypothesized that treating the aged heart with the small molecule MIF agonist (MIF20) can reinforce protective MIF signaling in cardiomyocytes, leading to a beneficial effect against I/R stress. The administration of MIF20 at the onset of reperfusion was found to not only decrease myocardial infarct size but also preserves systolic function in the aged heart. Protection from I/R injury was reduced in mice with cardiomyocyte-specific Mif deletion, consistent with the mechanism of action of MIF20 to allosterically increase MIF affinity for its cognate receptor CD74. We further found MIF20 to contribute to the maintenance of mitochondrial fitness and to preserve the contractile properties of aged cardiomyocytes under hypoxia/reoxygenation. MIF20 augments protective metabolic responses by reducing the NADH/NAD ratio, leading to a decrease in the accumulation of reactive oxygen species (ROS) in the aged myocardium under I/R stress. We also identify alterations in the expression levels of the downstream effectors PDK4 and LCAD, which participate in the remodeling of the cardiac metabolic profile. Data from this study demonstrates that pharmacologic augmentation of MIF signaling provides beneficial homeostatic actions on senescent myocardium under I/R stress.

Different efficacy in myopia control: Comparison between orthokeratology and defocus-incorporated multiple segment lenses.

PURPOSE: To compare the efficiency of orthokeratology (OK) and defocus-incorporated multiple segment (DIMS) lenses in myopia control in children. METHODS: This prospective study involved 540 subjects (7-14 years) categorized into three groups: DIMS lenses (180 cases), OK lenses (180 cases), or single-vision spectacles (SVS) (180 cases). After a one-year follow-up, changes in axial length (AL) and differences among the groups were analyzed. The subjects were further divided into a low myopia degree subgroup (LM, -1.50 D ≤ SE ≤ -0.50 D), a moderate myopia degree subgroup (MM, -3.00 D ≤ SE ＜ -1.50 D), and a high myopia degree subgroup (HM, -5.00 D ≤ SE ＜ -3.00 D). A one-way ANOVA and multiple linear regression analysis were used to compare AL elongation and the factors influencing the different groups. RESULTS: A total of 496 (92 %) subjects completed the study. The mean AL change in the OK lenses, DIMS lenses, and SVS were 0.20±0.18 mm, 0.30±0.22 mm, and 0.38±0.19 mm, respectively (P < 0.001). In the LM subgroup, the OK and DIMS groups showed similar AL changes, but both exhibited slower changes than the SVS group (P = 0.001). In the MM and HM subgroups, the OK lens performed the shortest AL elongation compared with the DIMS lenses and SVS (P < 0.001). Multiple regression analysis showed that the AL change was associated with age (ß = -0.038 and P = 0.005), initial AL (ß = -0.010 and P = 0.011), initial SE (ß = 0.028 and P = 0.007), and interventions using OK lenses (ß = -0.172 and P = 0.020) and DIMS lenses (ß = -0.089 and P = 0.020). CONCLUSION: Over a one-year treatment period, OK and DIMS lenses can significantly retard AL elongation compared with SVS. In addition, the OK lenses were more effective than the DIMS lenses in controlling AL in patients with higher degrees of myopia.

Extracellular macrophage migration inhibitory factor (MIF) downregulates adipose hormone-sensitive lipase (HSL) and contributes to obesity.

Attenuation of adipose hormone sensitive lipase (HSL) may impair lipolysis and exacerbate obesity. We investigate the role of cytokine, macrophage migration inhibitory factor (MIF) in regulating adipose HSL and adipocyte hypertrophy. Extracellular MIF downregulates HSL in an autocrine fashion, by activating the AMPK/JNK signaling pathway upon binding to its membrane receptor, CD74. WT mice fed high fat diet (HFD), as well as mice overexpressing MIF, both had high circulating MIF levels and showed suppression of HSL during the development of obesity. Blocking the extracellular action of MIF by a neutralizing MIF antibody significantly reduced obesity in HFD mice. Interestingly, intracellular MIF binds with COP9 signalosome subunit 5 (Csn5) and JNK, which leads to an opposing effect to inhibit JNK phosphorylation. With global MIF deletion, adipocyte JNK phosphorylation increased, resulting in decreased HSL expression, suggesting that the loss of MIF's intracellular inhibitory action on JNK was dominant in Mif-/- mice. Adipose tissue from Mif-/- mice also exhibited higher Akt and lower PKA phosphorylation following HFD feeding compared with WT, which may contribute to the downregulation of HSL activation during more severe obesity. Both intracellular and extracellular MIF have opposing effects to regulate HSL, but extracellular actions predominate to downregulate HSL and exacerbate the development of obesity during HFD.

The RhoA GTPase regulates Type I Interferon Signaling in Systemic lupus erythematosus.

Objective: Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by abnormal activation of the type I interferon (IFN) pathway, which results in tissue inflammation and organ damage. We explored the role of the RhoA GTPase in the type I IFN activation pathway to provide a potential basis for targeting GTPase signaling for the treatment of SLE. Methods: Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) of SLE patients and healthy controls, and the mRNA expression levels of RhoA and IFN-stimulated genes were measured by SYBR Green quantitative reverse transcriptase-polymerase chain reaction. IFN-stimulated response element (ISRE)-luciferase reporter gene assays and Western blotting were conducted to asssess the biologic function of RhoA. An Enzyme-Linked Immunoassay (ELISA) measured C-X-C motif chemokine ligand 10(CXCL10)protein expression. Results: Our studies demonstrated that the expression of RhoA in the PBMCs of SLE subjects was significantly higher than healthy controls and positively correlated with type I IFN scores and type I IFN-stimulated gene (ISGs) expression levels. SiRNA-mediated knockdown of RhoA and the RhoA/ROCK inhibitor Y27632 reduced the activity of the type I IFN-induced ISRE, the signal transducer and activator of transcription 1 (STAT-1) phosphorylation, and the expression of CXCL10 and 2'-5'-oligoadenylate synthetase 1(OAS1). Finally,we verified that Y27632 could significantly down-regulate the OAS1 and CXCL10 expression levels in PBMCs of SLE patients. Conclusion: Our study shows that RhoA positively regulates the activation of the type I IFN response pathway. Reducing the expression level of RhoA inhibits the abnormal activation of the type I IFN system, and the RhoA/ROCK inhibitor Y27632 decreases aberrant type I IFN signaling in SLE PBMCs, suggesting the possibility of targeting the RhoA GTPase for the treatment of SLE.

Urothelial Oxidative Stress and ERK Activation Mediate HMGB1-Induced Bladder Pain.

Activation of intravesical protease activated receptors-4 (PAR4) results in bladder pain through the release of urothelial macrophage migration inhibitory factor (MIF) and high mobility group box-1 (HMGB1). We aimed to identify HMGB1 downstream signaling events at the bladder that mediate HMGB1-induced bladder pain in MIF-deficient mice to exclude any MIF-related effects. We studied whether oxidative stress and ERK activation are involved by examining bladder tissue in mice treated with intravesical disulfide HMGB1 for 1 h and analyzed with Western blot and immunohistochemistry. HMGB1 intravesical treatment increased urothelium 4HNE and phospho-ERK1/2 staining, suggesting that HMGB1 increased urothelial oxidative stress and ERK activation. Furthermore, we examined the functional roles of these events. We evaluated lower abdominal mechanical thresholds (an index of bladder pain) before and 24 h after intravesical PAR4 or disulfide HMGB1. Intravesical pre-treatments (10 min prior) included: N-acetylcysteine amide (NACA, reactive oxygen species scavenger) and FR180204 (FR, selective ERK1/2 inhibitor). Awake micturition parameters (voided volume; frequency) were assessed at 24 h after treatment. Bladders were collected for histology at the end of the experiment. Pre-treatment with NACA or FR significantly prevented HMGB1-induced bladder pain. No significant effects were noted on micturition volume, frequency, inflammation, or edema. Thus, HMGB1 activates downstream urothelial oxidative stress production and ERK1/2 activation to mediate bladder pain. Further dissection of HMGB1 downstream signaling pathway may lead to novel potential therapeutic strategies to treat bladder pain.

A pref-1-controlled non-inflammatory mechanism of insulin resistance.

While insulin resistance (IR) is associated with inflammation in white adipose tissue, we report a non-inflammatory adipose mechanism of high fat-induced IR mediated by loss of Pref-1. Pref-1, released from adipose Pref-1+ cells with characteristics of M2 macrophages, endothelial cells or progenitors, inhibits MIF release from both Pref-1+ cells and adipocytes by binding with integrin ß1 and inhibiting the mobilization of p115. High palmitic acid induces PAR2 expression in Pref-1+ cells, downregulating Pref-1 expression and release in an AMPK-dependent manner. The loss of Pref-1 increases adipose MIF secretion contributing to non-inflammatory IR in obesity. Treatment with Pref-1 blunts the increase in circulating plasma MIF levels and subsequent IR induced by a high palmitic acid diet. Thus, high levels of fatty acids suppress Pref-1 expression and secretion, through increased activation of PAR2, resulting in an increase in MIF secretion and a non-inflammatory adipose mechanism of IR.

The Influence of Accommodation on Retinal Peripheral Refraction Changes in Different Measurement Areas.

Background: The change in refraction caused by accommodation inevitably affects the peripheral defocus state and thus may influence the effect of retinal peripheral myopic defocus measures in myopia control. This study investigated accommodation changes in different peripheral retinas under cycloplegia to help improve myopia control. Methods: Fifty-six eyes of fifty-six myopic subjects were recruited for this prospective study. The center and peripheral retina refractions were measured using multispectral refractive topography. The subjects were divided into low-to-moderate myopia group (range: -1.25 D to -6.00 D) and high myopia group (range: -6.25 D to -9.75 D) according to spherical equivalent (SE). The compound tropicamide (0.5% tropicamide and 0.5% phenylephrine) was used to relax the accommodation. The difference between cycloplegia and non-cycloplegia peripheral retinal refraction was analyzed using the t-test. The correlation between eccentricity and changes in peripheral refraction was analyzed using Pearson's correlation analysis. Results: The manifest refraction of the retina significantly decreased with an increase in eccentricity after cycloplegia. The annular refraction difference value at 50°-53° (ARDV 50-53) showed the largest refraction decrease of 1.31 D compared with the central retinal refraction decrease of 0.84 D. The inferior quadrantal refraction difference value had the least change compared to the other quadrants. The relative peripheral refraction (RPR) changes in refraction difference value (RDV) at 15° (RDV-15), RDV-30, and RDV-45 were less than 0.15 D. When the range of annulus narrowed to 5°, the narrower annulus showed faster change with eccentricity increase in ARDV 30-35, ARDV 35-40, ARDV 40-45, ARDV 45-50, and ARDV 50-53. The RPR was highly correlated with eccentricity (R = 0.938 and P < 0.001). The high myopia group had a greater hyperopic shift in the periphery than the low-to-moderate group after cycloplegia. Conclusions: Peripheral refraction showed a significant hyperopic shift after cycloplegia with an increase in eccentricity. The RPR became more hyperopic than the central refraction. The high myopia group showed more hyperopic shifts in the peripheral region. Accommodation should be taken into consideration in peripheral defocus treatment.

Effects of Orthokeratology Lens Decentration Induced by Paracentral Corneal Asymmetry on Axial Length Elongation.

BACKGROUND: To determine the influence of the magnitude of treatment zone decentration on axial length (AL) elongation and to investigate the association between paracentral corneal asymmetry and orthokeratology (OK) lens decentration. METHODS: This retrospective study involved 268 subjects (7-14 years) who wore OK lenses for one year. The parameters that reflected the paracentral corneal asymmetry were recorded: corneal toricity; Q value; anterior corneal curvature; and elevation values at the 6-, 7-, and 8-mm chords along the horizontal meridian. The relationships between these data and the amount of treatment zone decentration were analyzed. The relationship of the decentration magnitude and AL elongation was also analyzed. RESULTS: AL elongation was significantly associated with initial age, baseline spherical equivalent, AL, and the decentration magnitude. The subjects with large decentration magnitude showed less AL elongation. The decentration was affected by corneal morphology at the 8-mm chord on the nasal side. In the low curvature group (≤41.0D), the decentration magnitude had a stronger correlation with AL elongation than in all subjects. In the high curvature group (>41.0D), the decentration magnitude was no longer correlated with the AL elongation. CONCLUSION: The decentration of the OK lens effectively slowed the elongation of the eyeball. When the nasal curvature was less than 41.0 D at the 8-mm chord, the magnitude of decentration was predetermined by the flatter curve.

The impact of triglyceride-glucose index on ischemic stroke: a systematic review and meta-analysis.

BACKGROUND: Strokes significantly impair quality of life and incur high economic and societal burdens. The triglyceride and glucose (TyG) index is a biochemical marker of insulin resistance (IR) and may have important value in the prediction of strokes, especially ischemic stroke (IS). Our study aims to investigate the relationship between TyG index and IS and ascertain whether TyG index is independently associated with IS adverse outcomes. METHODS: The Cochrane, Embase, Medline, Web of Science, PubMed, and other relevant English databases and related websites were systematically searched for articles on ''TyG index'' and "stroke" published from inception to April 4, 2022. We reviewed the available literature on the TyG index and its relation to predicting IS occurrence in the general population and adverse clinical outcomes. We calculated odds ratios (OR) of TyG index and its predictability of IS occurrence and adverse outcomes. Statistical analyses were performed using the Meta Package in STATA, version 12.0. RESULTS: A total of 18 studies and 592,635 patients were included in our analysis. The pooled effect values of all stroke types showed that higher TyG index was associated with increased the risk of IS in the general population (OR 1.37; 95% CI 1.22-1.54) in a total sample of 554,334 cases with a high level of heterogeneity (P = 0.000, I2 = 74.10%). In addition, compared to IS patients with a lower TyG index, IS patients with a higher TyG index was associated with higher risk of stroke recurrence (OR: 1.50; 95% CI 1.19-1.89) and increased risk of mortality (OR 1.40 95% CI 1.14-1.71). No correlation was found in the effect value combinations of poor functional outcomes (OR 1.12; 95% CI 0.88-1.43) and neurological worsening (OR: 1.76; 95% CI 0.79-3.95) in a total sample of 38,301 cases with a high level of heterogeneity (P = 0.000; I2 = 77.20%). CONCLUSIONS: TyG index has potential value in optimizing risk stratification for IS in the general population. Furthermore, there is a significant association between high TyG index and many adverse outcomes of stroke, especially stroke recurrence and high mortality. Future studies should focus on multi-center and multi-regional designs in order to further explore the relationship between IS and TyG index.

A systematic review and meta-analysis of the prevalence and correlation of mild cognitive impairment in sarcopenia.

Sarcopenia is a progressive skeletal muscle disorder involving the loss of muscle mass and function, associated with an increased risk of disability and frailty. Though its prevalence in dementia has been studied, its occurrence in mild cognitive impairment (MCI) has not been well established. As MCI is often a prelude to dementia, our study aims to investigate the prevalence of MCI among individuals with sarcopenia and to also ascertain whether sarcopenia is independently associated with MCI. The Cochrane Library, PubMed, Ovid, Embase and Web of Science were systematically searched for articles on MCI and/or sarcopenia published from inception to 1 February 2022. We reviewed the available literature on the number of individuals with MCI and/or sarcopenia and calculated odds ratios (ORs) of sarcopenia in MCI and MCI in sarcopenia, respectively. Statistical analyses were performed using the meta package in Stata, Version 12.0. A total of 13 studies and 27 428 patients were included in our analysis. The pooled prevalence of MCI in participants with sarcopenia was 20.5% (95% confidence interval [CI]: 0.140-0.269) in a total sample of 2923 cases with a high level of heterogeneity (P < 0.001; I2  = 95.4%). The overall prevalence of sarcopenia with MCI was 9.1% (95% CI: 0.047-0.134, P < 0.001; I2  = 93.0%). For overall ORs, there were 23 364 subjects with a mean age of 73 years; the overall adjusted OR between MCI and sarcopenia was 1.46 (95% CI: 1.31-1.62). Slight heterogeneity in both adjusted ORs (P = 0.46; I2  = 0%) was noted across the studies. The prevalence of MCI is relatively high in patients with sarcopenia, and sarcopenia may be a risk factor for MCI.

Repeatability and correlation of corneal biomechanical measurements obtained by Corvis ST in orthokeratology patients.

PURPOSE: To evaluate the repeatability of the corneal biomechanical measurements obtained by Corvis ST in post-orthokeratology patients and analyze the correlation between the biomechanical and ocular parameters. METHODS: Fifty-one eyes of 51 myopic subjects were included in this study. The biomechanical parameters were assessed using Corvis ST. Repeatability was assessed using one-way ANOVA based on within-subject standard deviation (Sw), repeatability coefficient (RC), intraclass correlation coefficient (ICC) and correlation of variation (CoV). The correlation was evaluated using Pearson correlation analysis. RESULTS: All parameters measured by Corvis ST, except length of flattened cornea at the first and second applanations (A1L and A2L), showed a good intraobserver repeatability after a 3-month follow-up period. The ICC values for A1L and A2L were 0.444 and 0.654, whereas the other parameters were higher than 0.8. Similar trends were obtained for CoV, wherein the CoV values for A1L and A2L were greater than 13 %. The corneal biomechanical parameters were correlated with age, refraction, axial length (AL), steep and flat keratometry before and after orthokeratology, and central corneal thickness (CCT). Following orthokeratology treatment, post-keratometry demonstrated a higher correlation with stiffness parameter at first applanation (SP-A1), velocity of corneal apex at the first applanation (A1V), and radius than pre-keratometry, which showed a weak correlation with SP-A1. CONCLUSION: Corneal biomechanical parameters assessed using Corvis ST demonstrated a good repeatability, except A1L and A2L. The corneal biomechanical parameters were correlated with age, refraction, AL and pre- and post-keratometry. Thus, Corvis ST is a suitable device for investigating biomechanical parameter.

Clinical features and high-risk indicators of central nervous system involvement in primary Sjögren's syndrome.

BACKGROUND: Evidence for central nervous system involvement in primary Sjögren's syndrome (pSS) patients is controversial and extremely limited. We aimed to describe the clinical profiles and high-risk indicators of primary Sjögren's syndrome (pSS) patients with central nervous system (CNS) involvement (pSS-CNS). METHODS: A total of 412 participants with pSS from a hospital in China from January 2012 to December 2019 were enrolled in the retrospective study. 42 pSS-CNS patients were compared with 370 pSS patients without CNS involvement. The clinical features, laboratory examinations, imaging characteristics, and treatment of the pSS-CNS cases were systematically analyzed. Potential risk factors related to pSS-CNS patients were identified by multivariate logistic regression analysis. RESULTS: The prevalence of central nervous system involvement in the studied pSS patients was 10.2% (42/412), with 31.3% (14/42) of pSS patients having neurological manifestations as the initial symptom. The manifestations of hemiparesis (35.7%, 15/42), paraparesis (28.6%, 12/42), dysphonia (31.0%, 13/42), blurred vision (21.4%, 9/42), and dysfunctional proprioception (23.8%, 10/42) were more common in the pSS-CNS patients. Cerebral infarction (57.1%, 24/42), demyelination (31.0%, 13/42), myelitis (23.8%, 11/42), and angiostenosis (21.4%, 9/42) were most often found on MRI or CT scan imaging in the pSS-CNS patients. Intrathecal IgG level and total protein of cerebrospinal fluid were increased in 50% (8/16) of the pSS-CNS group. In comparison with patients without CNS involvement, the pSS-CNS patients were found to also have kidney and lung involvement, hematologic abnormalities, positive ANA and anti-SSA antibody tests, and reduced complement 3 (C3) and complement 4 (C4) levels (all p < 0.05). The prevalence of lung involvement, immune thrombocytopenia, and high-titer ANA (1:1000) were significantly higher in pSS-CNS disease activity compared to those in the moderately active group. Multivariate analysis identified lung involvement, anti-SSA positivity, and low C3 levels as prognostic factors for pSS-CNS. After high-dose glucocorticoids and immunosuppressive therapy, 60.5% (26/38) of pSS-CNS patients improved, 36.8% (14/38) were unresponsive to treatment, and 2.6% (1/38) died. CONCLUSION: Clinical features are diverse in pSS-CNS patients, and the morbidity rate is low. CNS involvement was the initial presentation in state percentage here pSS patients. Pulmonary involvement, a positive anti-SSA antibody test, and reduced C3 levels are potential risk factors for CNS involvement in pSS. Treatment with high-dose glucocorticoids and immunosuppressive therapy appeared effective in 60% of pSS-CNS patients. Key Points • The CNS manifestations of pSS are diverse, and CNS imaging and CSF analysis are important for the diagnosis. • Pulmonary involvement, positive anti-SSA, and reduced C3 levels are potential risk factors of pSS-CNS. • About 60% of pSS-CNS patients were responsive to high-dose glucocorticoid administration and immunosuppressive therapy.

CD74 as a regulator of transcription in normal B cells.

CD74 is receptor for the cytokine macrophage migration inhibitory factor (MIF). MIF binding to CD74 induces a signaling cascade resulting in the release of its cytosolic intracellular domain (CD74-ICD) that serves as a transcriptional regulator in chronic lymphocytic leukemia (CLL) cells. In the current study, we investigated the transcriptional and regulatory function of CD74-ICD in normal B cells. We show that following activation, CD74-ICD forms a complex in the cytosol with transcription factors, like PAX5, and binds the chromatin at a significantly higher number of sites compared with its binding in CLL cells. The expression of a major portion of these bound genes is shut down in the malignant cells. The CD74-ICD:PAX5 complex binds the promoter areas of a tumor-suppressor gene, DMTF1, and downregulates its expression through inhibition of transcription. These findings can help identify novel therapeutic pathways that are regulated during oncogenic transformation and are targets for future treatments.

Incidence and Risk Factors of Repositioning Surgery to Correct Misalignment of Toric Intraocular Lenses After Cataract Surgery：A Single-Center Retrospective Observational Study.

PURPOSE: To analyze the incidence and outcomes of repositioning surgery to correct misalignment of several toric intraocular lenses (IOLs) after cataract surgery. METHODS: In this retrospective study, patients who underwent repositioning surgery to correct misalignment of toric IOLs following cataract surgery between January 2019 and December 2021 were enrolled. The medical data on patients' age, gender, preoperative axial length, corneal astigmatism, the axis of astigmatism, IOL models, IOL axis, uncorrected distance visual acuity, residual refraction, and postoperative outcomes were analyzed. RESULTS: Among the 1135 eyes implanted with toric IOLs at Qingdao Eye Hospital, 23 (2.026%, 23/1135) underwent repositioning surgery. Univariate analysis revealed that the incidence of repositioning surgery was significantly lower with AcrySof (0.636%, 5/786) than with ZEISS (2.959%, 5/169) and TECNIS (7.222%, 13/180) IOL platforms; The incidence of repositioning surgery with monofocal toric IOLs (1.169%, 11/941) was significantly lower than multifocal toric IOLs (6.186%, 12/194) (P<0.001); Additionally, a significant difference in age was also observed (P=0.002). Multivariate logistic regression analysis showed that IOL platform (P=0.004) and younger age (P=0.006) were independent risk factors for repositioning surgery. CONCLUSION: The incidence of repositioning surgery of toric IOLs after cataract surgery was 2.026%. It was linked to the IOL platform, multifocal toric IOLs, and younger age.

Macrophage Migration Inhibitory Factor (MIF) Promotes Increased Proportions of the Highly Permissive Th17-like Cell Profile during HIV Infection.

In this study, we evaluate the role of the MIF/CD74 axis in the functionality of CD4+ T lymphocytes (CD4TL) during HIV infection. MDMs from healthy donors were infected with a R5-tropic or Transmitted/Founder (T/F) HIV strain. At day 11 post-MDM infection, allogeneic co-cultures with uninfected CD4TLs plus MIF stimulus were performed. Cytokine production was evaluated by ELISA. MIF plasma levels of people with HIV (PWH) were evaluated by ELISA. The phenotype and infection rate of CD4TLs from PWH were analyzed after MIF stimulus. Intracellular cytokines and transcription factors were evaluated by flow cytometry. Data were analyzed by parametric or non-parametric methods. The MIF stimulation of HIV-infected MDMs induced an increased expression of IL-6, IL-1ß and IL-8. In CD4TL/MDM co-cultures, the MIF treatment increased IL-17A/RORγt-expressing CD4TLs. Higher concentrations of IL-17A in supernatants were also observed. These results were recapitulated using transmitted/founder (T/F) HIV-1 strains. The MIF treatment appeared to affect memory CD4TLs more than naïve CD4TLs. MIF blocking showed a negative impact on IL17A+CD4TL proportions. Higher MIF concentrations in PWH-derived plasma were correlated with higher IL-17A+CD4TL percentages. Finally, MIF stimulation in PWH-derived PBMCs led to an increase in Th17-like population. MIF may contribute to viral pathogenesis by generating a microenvironment enriched in activating mediators and Th17-like CD4TLs, which are known to be highly susceptible to HIV-1 infection and relevant to viral persistence. These observations establish a basis for considering MIF as a possible therapeutic target.

Temporal and spatial characterization of myopia in China.

Purpose: The aim of this study was to characterize the temporal and spatial distribution of myopia among students aged 7-18 years, by analyzing the aggregation area and providing the basis for the prevention and control of myopia in China. Methods: A database for the spatial analysis of myopia in China during 1995-2014 was established using ArcGIS10.0 software as a platform for data management and presentation. A spatial autocorrelation analysis of myopia was undertaken, and a temporal and spatial scan analysis was performed using SaTScan9.5 software. Results: Our data demonstrated that the prevalence of myopia in China in 1995, 2000, 2005, 2010, and 2014 was 35.9, 41.5, 48.7, 57.3, and 57.1%, respectively, thus indicating a gradual upward trend. The prevalence of myopia was analyzed in various provinces (municipalities and autonomous regions), and the highest was found in Jiangsu Province, with an average Moran's I index of 0.244295 in China (P ≤ 0.05). According to the local Moran's I autocorrelation analysis, there was a spatial aggregation of myopia prevalence among students in the entire country, with Shandong, Jiangsu, Anhui, and Shanghai being classified as high-high aggregation areas, while Hainan and Guangxi were classified as low-low aggregation areas. In addition, the Getis-Ord General G results of the global hotspot analysis showed a countrywide myopia prevalence index of 0.035020 and a Z score of 1.7959 (P = 0.07251). Because the myopia prevalence correlation difference was not statistically significant, there were no "positive hotspots" or "negative hotspots." The local hotspot analysis shows that Shandong and Jiangsu belong to high-value aggregation areas, while Hainan and Guizhou belong to low-value aggregation areas. Further analysis using time-space scanning showed 15 aggregation regions in five stages, with four aggregation regions having statistically significant differences (P ≤ 0.05). However, the aggregation range has changed over time. Overall, from 1995 to 2014, the aggregation areas for the myopia prevalence in Chinese students have shifted from the northwest, north, and northeast regions to the southeast regions. Conclusion: Our data demonstrate that, from 1995 to 2014, the prevalence of myopia increased in students aged 7-18 years in China. In addition, the prevalence of myopia is randomly distributed in various provinces (municipalities and autonomous regions) and exhibits spatial aggregation. Also, the gathering area is gradually shifting to the southeast, with the existence of high-risk areas. It is, therefore, necessary to focus on this area and undertake targeted prevention and control measures.