ASSOCIATION BETWEEN PLASMA TRANSFUSION AND IN-HOSPITAL MORTALITY IN CRITICALLY ILL PATIENTS WITH SEPSIS-INDUCED COAGULOPATHY.

ABSTRACT: Background: Plasma is commonly used in patients with coagulopathy; however, its role in patients with sepsis-induced coagulopathy (SIC) is unclear. This study aimed to evaluate the effect of plasma transfusion on the prognosis of patients with SIC. Methods: Data were collected from the Medical Information Mart for Intensive Care IV database. Multivariable logistic regression analysis was used to determine the association between plasma transfusion and the incidence of in-hospital mortality, pulmonary embolism, and lower extremity deep vein thrombosis in critically ill patients with SIC. Propensity score matching (PSM) and propensity score-based inverse probability of treatment weighting (IPTW) models were used to ensure the robustness of our findings. Furthermore, the nonparametric relationship between in-hospital mortality and plasma transfusion volume was analyzed using restricted cubic spline. Subgroups analyses were performed for age, sex, Charlson score, Sequential Organ Failure Assessment score, SIC score, and with hemorrhage. Results: A total of 8,747 patients with SIC were enrolled: of them, 1874 were in the plasma infusion group, and 6,873 were in the no plasma infusion group. Compared with the no plasma infusion group, the plasma infusion group had higher in-hospital mortality (odds ratio [OR], 1.4411; 95% confidence interval [CI], 1.2280-1.6897, P < 0.05), and the results were robust after PSM (OR, 1.3227; 95% CI, 1.1152-1.5697; P < 0.05) and IPTW (OR, 1.1541; 95% CI, 1.0738-1.2404; P < 0.05). Similar results were also observed in different subgroups. However, because of conflicting results after PSM and IPTW, we were unable to definitively link plasma transfusion with pulmonary embolism and deep vein thrombosis. Compared with the no early plasma transfusion group (≥12 h), the in-hospital mortality rate was lower in the early plasma transfusion group (<12 h) (OR, 0.5426; 95% CI, 0.4398-0.6844; P < 0.05). The restricted cubic spline analysis indicated that increased plasma transfusion was associated with increased in-hospital mortality in patients with SIC. Conclusion: Plasma transfusion increases in-hospital mortality in patients with SIC, and the mortality rate increases with the amount of plasma transfusion. Patients with SIC who received early plasma infusion had lower in-hospital mortality than those who received no early plasma transfusion.

Fabrication of Ag-CaCO3 Nanocomposites for SERS Detection of Forchlorfenuron.

In this study, Ag-CaCO3 nanocomposites were synthesized using silver nitrate as the precursor solution based on calcium carbonate nanoparticles (CaCO3 NPs). The synthesis involved the reaction of calcium lignosulphonate and sodium bicarbonate. The properties of Ag-CaCO3 nanocomposites were studied by various technologies, including an ultraviolet-visible spectrophotometer, a transmission electron microscope, and a Raman spectrometer. The results showed that Ag-CaCO3 nanocomposites exhibited a maximum UV absorption peak at 430 nm, the surface-enhanced Raman spectroscopy (SERS) activity of Ag-CaCO3 nanocomposites was evaluated using mercaptobenzoic acid (MBA) as the marker molecule, resulting in an enhancement factor of 6.5 × 104. Additionally, Ag-CaCO3 nanocomposites were utilized for the detection of forchlorfenuron. The results demonstrated a linear relationship in the concentration range of 0.01 mg/mL to 2 mg/mL, described by the equation y = 290.02x + 1598.8. The correlation coefficient was calculated to be 0.9772, and the limit of detection (LOD) was determined to be 0.001 mg/mL. These findings highlight the relatively high SERS activity of Ag-CaCO3 nanocomposites, making them suitable for analyzing pesticide residues and detecting toxic and harmful molecules, thereby contributing to environmental protection.

A randomized, double-blind, placebo-controlled phase II study to evaluate the efficacy and safety of ivarmacitinib (SHR0302) in adult patients with moderate-to-severe alopecia areata.

BACKGROUND: Alopecia areata (AA) is a CD8+ T cell-mediated autoimmune disease characterized by nonscarring hair loss. Ivarmacitinib, which is a selective oral Janus kinase 1 inhibitor, may interrupt certain cytokine signaling implicated in the pathogenesis of AA. OBJECTIVE: To evaluate the efficacy and safety of ivarmacitinib in adult patients with AA who have ≥25% scalp hair loss. METHODS: Eligible patients were randomized 1:1:1:1 to receive ivarmacitinib 2, 4, or 8 mg once daily or placebo for 24 weeks. The primary end point was the percentage change from baseline in the Severity of Alopecia Tool score at week 24. RESULTS: A total of 94 patients were randomized. At week 24, the least squares mean difference in the percentage change from baseline in the Severity of Alopecia Tool score for ivarmacitinib 2, 4, and 8 mg and placebo groups were -30.51% (90% CI, -45.25, -15.76), -56.11% (90% CI, -70.28, -41.95), -51.01% (90% CI, -65.20, -36.82), and -19.87% (90% CI, -33.99, -5.75), respectively. Two serious adverse events-follicular lymphoma and COVID-19 pneumonia-were reported. LIMITATIONS: A small sample size limits the generalizability of the results. CONCLUSION: Treatment with ivarmacitinib 4 and 8 mg doses in patients with moderate and severe AA for 24 weeks was efficacious and generally tolerated.

Biofilm microenvironment-responsive polymeric CO releasing micelles for enhanced amikacin efficacy.

Biofilm-associated infections (BAI) have posed serious threats to public health. Novel therapy based on carbon monoxide (CO) is being increasingly appreciated. However, CO therapy like inhaled gas treatment was impeded owing to its low bioavailability. Besides, the direct use of CO releasing molecules (CORM) showed low therapeutic efficacy in BAI. Therefore, it is vital to improve the efficiency of CO therapy. Herein, we proposed polymeric CO releasing micelles (pCORM) from self-assembly of amphiphilic copolymers containing CORM bearing block as hydrophobic part and acryloylmorpholine block as hydrophilic part. The catechol modified CORM were conjugated through pH cleavable boronate ester bonds and releasing CO passively under biofilm microenvironment. When combined with subminimal inhibitory concentration antibiotic amikacin, pCORM could significantly enhance its bactericidal efficiency against biofilm-encapsulated multidrug-resistant bacteria, representing a promising approach to combat BAI.

Elevated Neuropeptides in Dry Eye Disease and Their Clinical Correlations.

PURPOSE: The goal of this study was to assess neuropeptide levels in patients with dry eye disease (DED) and investigate their correlations with clinical characteristics. METHODS: This study included 38 eyes of 38 patients diagnosed with DED (DED group) and 38 eyes of 38 healthy volunteers without DED (control group). Ocular surface evaluation was performed. The severity of dry eye symptoms and signs in the DED group was graded. Neuropeptides [substance P (SP), alpha-melanocyte-stimulating hormone (α-MSH), ß-endorphin, neurotensin, and oxytocin] and inflammatory cytokines levels were measured in basal tears. The link between neuropeptides and clinical parameters was investigated using Spearman rank correlation. RESULTS: Overall, 76.3% of patients in the DED group showed dry eye symptoms and signs that were inconsistent in severity. Compared with the control group, the DED group showed higher levels of SP, α-MSH, and oxytocin in tears (P = 0.012, P = 0.030, and P = 0.006, respectively), but similar levels of ß-endorphin and neurotensin (P = 0.269 and P = 0.052). The levels of SP, α-MSH, and oxytocin were elevated in DED patients with higher grading of symptoms than clinical signs (all P < 0.05). SP, α-MSH, and oxytocin levels in tears were positively correlated with Ocular Surface Disease Index scores, frequency of sensitivity to light, and frequency of blurred vision (all P < 0.05). CONCLUSIONS: The increased tear levels of SP, α-MSH, and oxytocin may be linked to ocular discomfort in DED. Neuropeptides may play a key role in the development of DED, especially in DED patients with more severe symptoms than clinical signs.

Prospective clinical study of retinal microvascular alteration after ICL implantation.

Purpose: To evaluate the retinal microvascular alteration after implantable collamer lens (ICL) implantation in moderate to high myopia patients using quantitative optical coherence tomography angiography (OCTA). Methods: This prospective cohort study included 50 eyes of 25 patients with preoperative spherical equivalent ≥ -3.00 D. Patients underwent bilateral ICL implantation at the Department of Ophthalmology, Peking University Third Hospital, from November 2018 to July 2019. OCTA was used to image the superficial and deep retinal capillary plexuses before ICL implantation surgery and at 3 months follow-up. Results: There was no significant difference in the microvascular density within each annular zone and all quadrantal zones of the superficial and deep layers found in myopia patients before and after ICL surgery. Conclusion: Levels of microvascular density in retinal capillary plexuses were stable, as detected by the OCTA, showing the high security of ICL implantation, which would not leave adverse effects on retinal microvasculature in myopia patients.

Progress of Bulbar Conjunctival Microcirculation Alterations in the Diagnosis of Ocular Diseases.

Bulbar conjunctival microcirculation is a microvascular system distributed in the translucent bulbar conjunctiva near the corneal limbus. Multiple ocular diseases lead to bulbar conjunctival microcirculation alterations, which means that bulbar conjunctival microcirculation alterations would be potential screening and diagnostic indicators for these ocular diseases. In recent years, with the emergence and application of a variety of noninvasive observation devices for bulbar conjunctiva microcirculation and new image processing technologies, studies that explored the potential of bulbar conjunctival microcirculation alterations in the diagnosis of ocular diseases have been emerging. However, the potential of bulbar conjunctival microcirculation alterations as indicators for ocular diseases has not been exploited to full advantage. The observation devices, image processing methods, and algorithms are not unified. And large-scale research is needed to concrete bulbar conjunctival microcirculation alterations as indicators for ocular diseases. In this paper, we provide an update on the progress of bulbar conjunctival microcirculation alterations in the diagnosis of ocular diseases in recent five years (from January 2017 to March 2022). Relevant ocular diseases include contact lens wearing, dry eye, conjunctival malignant melanoma, conjunctival nevus, and diabetic retinopathy.

Effects of different types of non-cardiac surgical trauma on hippocampus-dependent memory and neuroinflammation.

Background: Older individuals have been reported to suffer from cognitive disorders after surgery. Various types of surgical trauma have been used to establish postoperative cognitive dysfunction (POCD) animal models in preclinical studies. However, few comparative analyses of these animal models were conducted. Methods: Tibial surgery, abdominal surgery, and extended abdominal surgery were performed on aged ICR mice to establish POCD models. Behavioral tests included open field, novel object recognition, fear conditioning, and Morris water maze tests. The Z-score methodology was adopted to obtain a comprehensive and integrated memory performance profile. The changes in hippocampal neuroinflammation were analyzed by ELISA, PCR, and immunofluorescence. Results: In this study, we found that each type of non-cardiac surgical trauma has a different effects on locomotor activity. Tibial and extended abdominal surgeries led to more significant cognitive impairment than abdominal surgery. Inflammatory cytokines peaked on postoperative day 1 and decreased to control levels on days 3 and 7. Hippocampal neuroinflammation indicators between the three surgery types on postoperative day 1 had no statistical differences. Conclusion: Overall, the type and intensity of non-cardiac surgical trauma can affect cognitive behavioral outcomes and central inflammation. The shortcomings and emerging issues of POCD animal research methods need to be further studied and solved.

Evaluation of Ocular Surface Characteristics in Dry Eye Disease With and Without Soft Contact Lens Wear: A Comparative Study.

OBJECTIVES: To investigate ocular surface alterations and in vivo confocal microscopic characteristics of the cornea in dry eye disease (DED) with contact lens wear (CLW). METHODS: Sixty participants were divided into three groups: DED with CLW (n=20), DED without CLW (n=20), and normal control (n=20). Ocular surface parameters were evaluated. Basal tears and in vivo confocal microscopy images of the cornea were collected. Multiplex bead analysis was used to assess interleukin (IL)-6, IL-1ß, tumor necrosis factor (TNF)-α, nerve growth factor (NGF), and substance P (SP) in tears. Nerve morphology and dendritic cell density in corneal subbasal nerve images were calculated. RESULTS: The DED with CLW group showed significantly higher ocular surface staining scores ( P =0.022) and higher levels of IL-1ß, NGF, and SP in tears ( P =0.014, P =0.004 and P =0.025) than the DED without CLW group. Corneal dendritic cell density in the DED with CLW group was significantly higher than that in the normal controls ( P =0.001) and DED without CLW group ( P =0.043). Tear cytokine levels of IL-1ß, NGF, and SP were correlated with ocular surface parameters in the DED with CLW group. Moreover, the years of CLW were positively correlated with corneal dendritic cell density (r=0.527, P =0.017) and negatively correlated with corneal nerve density (r=-0.511, P =0.021). CONCLUSIONS: Patients with DED with CLW showed greater epithelial damage, elevated inflammatory cytokines and neuromediators in tears, and higher corneal dendritic cell density than patients with DED without CLW. The immune and nervous systems may be involved in contact lens-related DED.

Evaluations of wavefront aberrations and corneal surface regularity in dry eye patients measured with OPD Scan III.

AIM: To compare the wavefront aberrations and corneal surface regularity between dry eye (DE) patients and normal subjects and assess its diagnostic performance for DE measured with OPD Scan-III. METHODS: Fifty right eyes of 50 DE patients and 31 right eyes of normal subjects were included. The examinations for ocular surface including logarithm of the minimum angle of resolution best-corrected distance visual acuity (logMAR BCVA) the ocular surface disease index (OSDI), tear film break-up time (TBUT) and corneal fluorescein staining (CFS). OPD Scan-III was used to measure anterior corneal aberrations including total corneal aberrations, high order aberration (HOA), coma, trefoil, spherical aberration (SA), standard deviation of corneal power (SDP), surface regularity index (SRI) and surface asymmetry index (SAI). Statistical analysis were assessed with nonparametric tests and Spearman's correlations. All parameters were also analyzed for sensitivity, specificity, and receiver operating characteristics (ROC) curves. RESULTS: Wavefront aberrations parameters including total corneal aberrations, HOA, coma, trefoil, and SA in DE group were significantly higher than those in normal group (P<0.001). Corneal surface regularity parameters including SRI and SAI in DE group were significantly higher than both in normal group (P<0.05). All the wavefront aberrations parameters had significant correlations with ocular surface parameters (P<0.05). The logMAR BCVA had positive correlations with SAI and SRI (all P<0.001). CFS scores had positive correlations with SAI and SRI (all P<0.001). All the wavefront aberrations parameters showed good diagnosis sensitivity and specificity, however, the corneal regularity parameters showed only good specificity but poor sensitivity. The cut-off value selected for trefoil in diagnosis DE showed the highest area under the curve (AUC, 0.921) values as compared to the other parameters with sensitivity of 0.955 and specificity of 0.867. CONCLUSION: Wavefront aberrations and corneal surface regularity are increased in DE patients and also correlated with ocular surface parameters. Wavefront aberrations parameters have potential to be indicators to diagnosis and monitor DE.

Motion Detecting, Temperature Alarming, and Wireless Wearable Bioelectronics Based on Intrinsically Antibacterial Conductive Hydrogels.

Hydrogels have attracted considerable interest in developing flexible bioelectronics such as wearable devices, brain-machine interface products, and health-monitoring sensors. However, these bioelectronics are always challenged by microbial contamination, which frequently reduces their service life and durability due to a lack of antibacterial property. Herein, we report a class of inherently antibacterial conductive hydrogels (ACGs) as bioelectronics for motion and temperature detection. The ACGs were composed of poly(N-isopropylacrylamide) (pNIPAM) and silver nanowires (AgNWs) via a two-step polymerization strategy, which increased the crosslink density for enhanced mechanical properties. The introduction of AgNWs improved the conductivity of ACGs and endowed them with excellent antibacterial activity against both Gram-positive and -negative bacteria. Meanwhile, pNIPAM existed in ACGs and exhibited a thermal responsive behavior, thereby inducing sharp changes in their conductivity around body temperature, which was successfully employed to assemble a temperature alarm. Moreover, ACG-based sensors exhibited excellent sensitivity (within a small strain of 5%) and the capability of capturing various motion signals (finger bending, elbow bending, and even throat vibrating). Benefiting from the superiority of ACG-based sensors, we further demonstrated a wearable wireless system for the remote control of a vehicle, which is expected to help disabled people in the future.

Role of P2X4/NLRP3 Pathway-Mediated Neuroinflammation in Perioperative Neurocognitive Disorders.

Several studies have demonstrated that neuroinflammation is the key to perioperative neurocognitive disorders (PND); however, the specific mechanism postsurgery and anesthesia has not yet been fully clarified. The present study is aimed at exploring the effects of P2X4/NLRP3 signaling pathway in neuroinflammation and cognitive impairment after surgery. 12-14-month-old male C57BL/6 mice undergoing open tibial fracture surgery by sevoflurane anesthesia were administered P2X4R inhibitor 5-BDBD or saline was intraperitoneally for 3 consecutive days after surgery. Then, the animals were subjected to Morris water maze test or sacrificed to collect the hippocampus. The level of P2X4R and NLRP3 was estimated by Western blot, the activation of microglia was detected via immunohistochemistry, and the expression of TNF-α, IL-1ß, and IL-6 was quantified by enzyme-linked immunosorbent assay. These results indicated that tibial surgery caused cognitive impairment, increased the expression of P2X4R and NLRP3, and aggravated the neuroinflammation and microglia activation. However, intraperitoneal injection of 5-BDBD attenuated these effects. In conclusion, these findings indicated that the P2X4/NLRP3 pathway might be involved in the pathophysiology of PND.

Binocular visual function after unilateral versus bilateral implantation of segmented refractive multifocal intraocular lenses: a pilot study.

PURPOSE: To evaluate binocular visual function after unilateral and bilateral implantation of segmented refractive multifocal intraocular lenses (MIOLs). METHODS: This prospective comparative pilot study included patients who underwent SBL-3 (Lenstec; + 3.00 D) implantation at Peking University Third Hospital. Patients were divided into two groups (monocular or binocular surgery). Thirty-two patients with emmetropic presbyopic contralateral eyes and 49 patients with bilateral SBL-3 implantation within a week between eyes were included in the unilateral SBL-3 and bilateral groups, respectively. At 3-month follow-up, the main outcomes were binocular uncorrected distant, intermediate, and near visual acuity (UDVA, UIVA, and UNVA). Secondary outcomes included binocular best-corrected visual acuity at all distances, defocus curve, contrast sensitivity, photic phenomena, spectacle independence, patient satisfaction, and National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) score. The essential perceptual phenomena constituting binocular vision, simultaneous perception, fusion, and stereopsis were also evaluated. RESULTS: Both groups showed similar binocular UDVA and UIVA, but UNVA was significantly better in the bilateral group (0.07 ± 0.07 versus 0.12 ± 0.07, P = 0.008). Better binocular defocus curve at intermediate to near focal points, higher percentage of spectacle independence at near distance, and NEI-VFQ-25 near activity scores were observed in the bilateral group. No significant differences in contrast sensitivity, photic phenomena, overall satisfaction, other NEI-VFQ-25 subscales, fusional amplitude, and stereoacuity were found between groups. CONCLUSION: Unilateral implantation of segmented refractive MIOL provided desirable distant visual acuity and high patient satisfaction, but inferior intermediate and near visual outcomes compared with bilateral implantation.

Clinical Study on the Efficacy of Laparoscopic Hepatectomy and Its Influence on the Expression of Serum VEGF, FGF, and Immune Function.

Liver cancer is one of the most common malignant tumors. Partial hepatectomy is the most basic and effective treatment for hepatocellular carcinoma because of its high operative effect and perioperative safety. Open surgery is the most traditional hepatectomy. Although it can completely remove tumor lesions and prolong patient survival, it has disadvantages such as large trauma and long postoperative recovery time. Meanwhile, long-term bed rest can increase the risk of complications such as venous thrombosis and infection. The advantages of laparoscopic partial hepatectomy, such as clear operative field, simple operation, little trauma, light surgical stress, quick postoperative recovery, and low complications, can avoid damage to vital organs, blood vessels, and nerves, which has been widely accepted and recognized in clinical practice.

Efficacy and Safety of SHR0302, a Highly Selective Janus Kinase 1 Inhibitor, in Patients with Moderate to Severe Atopic Dermatitis: A Phase II Randomized Clinical Trial.

BACKGROUND: Atopic dermatitis is a chronic, inflammatory condition causing a substantial burden to patients and caregivers. SHR0302 is an oral, highly selective, Janus kinase 1 inhibitor under investigation for inflammatory skin diseases. OBJECTIVE: The aim of this study was to investigate the efficacy and safety of SHR0302 in Chinese patients with moderate to severe atopic dermatitis. DESIGN AND SETTING: A randomized, double-blind, placebo-controlled, multicenter, phase II trial was conducted in China between October 2019 and August 2020. PARTICIPANTS: Patients (n = 105) aged 18-75 years with moderate to severe dermatitis and nonresponsive or intolerant to topical or conventional systemic treatments were included. INTERVENTIONS: Patients were randomly assigned in a ratio of 1:1:1 to receive SHR0302 4 mg once daily, SHR0302 8 mg once daily, or placebo for 12 weeks. MAIN OUTCOME MEASURES: The primary efficacy endpoint was the proportion of patients achieving Investigator's Global Assessment (IGA) response (IGA of 0 [clear] or 1 [almost clear] with improvement of ≥2 grades) at week 12. Secondary efficacy assessments included Eczema Area and Severity Index (EASI) and pruritus Numerical Rating Scale (NRS) scores. RESULTS: At week 12, IGA response was achieved in nine patients (25.7%; 90% confidence interval [CI] 13.6-37.9%; p = 0.022) in the SHR0302 4 mg group, 19 patients (54.3%; 90% CI 40.4-68.1%; p < 0.001) in the SHR0302 8 mg group, and two patients (5.7%; 90% CI 0.0-12.2%) in the placebo group. EASI75 was achieved in 51.4% (p = 0.013), 74.3% (p < 0.001), and 22.9% of patients in the SHR0302 4 mg, SHR0302 8 mg, and placebo groups, respectively, while an NRS ≥3-point improvement occurred in 65.7% (p < 0.001), 74.3% (p < 0.001), and 22.9% of patients, respectively. Treatment-emergent adverse events were reported in 60.0%, 68.6%, and 51.4% of patients in the SHR0302 4 mg, SHR0302 8 mg, and placebo groups, respectively. The adverse events were mild in most cases. Three serious adverse events were reported, all being worsening of atopic dermatitis. No serious infection was reported. CONCLUSIONS AND RELEVANCE: Oral SHR0302 was effective and well tolerated in Chinese adult patients with moderate to severe atopic dermatitis. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04162899; URL: https://clinicaltrials.gov/ . Date first registered: 14 November 2019.

Quantification of Increased Corneal Subbasal Nerve Tortuosity in Dry Eye Disease and Its Correlation With Clinical Parameters.

Purpose: This study quantified corneal subbasal nerve tortuosity in dry eye disease (DED) and investigated its correlation with clinical parameters by proposing an aggregated measure of tortuosity (Tagg). Methods: The sample consisted of 26 eyes of patients with DED and 23 eyes of healthy volunteers, which represented separately the dry eye group and the control group. Clinical evaluation of DED and in vivo confocal microscopy analysis of the central cornea were performed. Tagg incorporated six metrics of tortuosity. Corneal subbasal nerve images of subjects and a validation data set were analyzed using Tagg. Spearman's rank correlation was performed on Tagg and clinical parameters. Results: Tagg was validated using 1501 corneal nerve images. Tagg was higher in patients with DED than in healthy volunteers (P < 0.001). Tagg was positively correlated with the ocular surface disease index (r = 0.418, P = 0.003) and negatively correlated with tear breakup time (r = -0.398, P = 0.007). There was no correlation between Tagg and visual analog scale scores, corneal fluorescein staining scores, or the Schirmer I test. Conclusions: Tagg was validated for quantification of corneal subbasal nerve tortuosity and was higher in patients with DED than in healthy volunteers. A higher Tagg may be linked to ocular discomfort, visual function disturbance, and tear film instability. Translational Relevance: Corneal subbasal nerve tortuosity is a potential biomarker for corneal neurobiology in DED.

Enhanced store-operated calcium entry (SOCE) exacerbates motor neurons apoptosis following spinal cord injury.

Spinal cord injury is pathologically characterized by the loss of motor function caused by neurons apoptosis. Store-operated calcium entry (SOCE) is widely known to dictate the apoptosis of various cell types. To examine SOCE in spinal cord injury and explore the role of SOCE in apoptosis, patients with spinal cord injury (SCI) and SCI mouse models were included. Expression of SOCE components and apoptosis-related proteins were examined by Western blotting. Calcium imaging was used to assess SOCE activity. As a result, we confirmed the enhanced levels of ORAI1 and STIM1 in SCI patients and SCI mouse models. In vitro study, tunicamycin impaired the viability of VSC4.1 cells (motoneuron-neuroblastoma hybrid cell line) and increased SOCE activity, the effects of which could be abolished by 2-APB. Furthermore, tunicamycinreduced BCL-2/BAX ratio was also reversed by 2-APB. Additionally, EdU assay and DCFH-DA staining confirmed the regulatory role of 2-APB in proliferation and ROS production. Of note is the improved hindlimb motor function and alleviated depression by 2-APB administration. Therefore, we conclude that SOCE may contribute to the pathogenesis of SCI by exacerbating the apoptosis of motoneurons.

Pigment epithelium-derived factor (PEDF) plays anti-inflammatory roles in the pathogenesis of dry eye disease.

PURPOSE: To investigate the expression of pigment epithelium-derived factor (PEDF) in ocular surface in dry eye disease (DED) and its anti-inflammatory roles and mechanisms, clinically and by experiments in vivo and in vitro. METHODS: A cross-sectional study was conducted to detect the expression of PEDF in tears of dry eye patients by enzyme-linked immunosorbent assay (ELISA). Using dry eye mouse model and human corneal epithelial cells (hCECs) stimulated by hyperosmolarity or inflammatory cytokines, expression of PEDF in corneal epithelial cells, stroma and conjunctiva was quantified by real-time polymerase chain reaction, ELISA and Western blot. Next, either dry eye mice or hyperosmotic hCECs were treated with recombinant PEDF or neutralizing antibodies, and the expressions of inflammatory cytokines and immune cells were detected. Finally, Western blot was performed on MAPK and NF-κB to investigate the signaling pathways by which PEDF played its roles. RESULTS: Concentrations of PEDF were increased in tears of dry eye patients. Increased PEDF was observed in corneal epithelial cells (CECs) rather than corneal stroma or conjunctiva in dry eye mice. Furthermore, hCECs exposed to hyperosmolarity showed upregulation of PEDF. In vivo and in vitro studies showed that PEDF suppressed the expression of inflammatory cytokines including IL-1ß, IL-6, TNF-α and IL-17A, as well as the percentage of Th17 cells in DED. Further investigation showed that PEDF inhibited the phosphorylation of MAPK p38 and JNK in hyperosmotic hCECs. CONCLUSIONS: CECs derived PEDF is increased in DED. PEDF plays anti-inflammatory and immunoregulatory roles in the pathogenesis of DED.

Optical quality in patients with dry eye before and after treatment.

CLINICAL RELEVANCE: Dry eye disease could result in vision-related subjective symptoms even in patients with good best-corrected visual acuity. The standard deviation of corneal power and the surface asymmetry index could be indicators of treatment efficacy in dry eye. BACKGROUND: Few studies have examined changes in optical quality before and after dry eye treatment. Here, we evaluated changes in optical quality in patients with dry eye before and after treatment and identified potential indicators of dry eye-treatment efficacy. METHODS: Twenty-five right eyes of 25 untreated patients with dry eye were included. The same ocular-surface and optical-quality examinations were performed before and after two-weeks of treatment with hyaluronate in conjunction with fluorometholone eye drops. The Ocular Surface Disease Index, tear film break-up time, and corneal fluorescein staining were measured. Contrast sensitivity was used to measure resolution capability, the double-pass Optical Quality Analysis System to examine the modulation transfer function, Strehl ratio, and objective scattering index, and OPD Scan III to measure anterior corneal aberrations over 4-mm analytical zones including total corneal and high-order aberrations. The standard deviation of corneal power, surface regularity index, and surface asymmetry index were also measured. Paired sample t-tests and Spearman's correlations were used for the analyses. RESULTS: The Ocular Surface Disease Index, tear film break-up time, and corneal fluorescein staining improved after two weeks of treatment. Contrast sensitivity in photopic, photopic with glare, scotopic, and scotopic with glare conditions all improved (p < 0.05), as did the modulation transfer function, Strehl ratio, and objective scattering index (p = 0.001, p = 0.008, and p = 0.001, respectively). Total corneal aberrations and the surface regularity index did not significantly differ before and after treatment; corneal high-order aberrations, standard deviation of corneal power, and the surface asymmetry index significantly improved after treatment (p = 0.045, p = 0.019, and p = 0.049, respectively). Changes in standard deviation of corneal power and in surface asymmetry index correlated with change in corneal fluorescein staining (p = 0.006 and p = 0.007, respectively). CONCLUSION: Optical quality in patients with dry eye improved after treatment. The standard deviation of corneal power and surface asymmetry index could be indicators of treatment efficacy in dry eye.

Silicone Oil-Associated Extensive Intraocular Ossification: A case report.

BACKGROUND: Intraocular ossification is an uncommon calcium deposition process associated with trauma, chronic inflammation, tumor, and long-standing retinal detachment. This is the first reported extensive intraocular bone formation associated with silicone oil. CASE PRESENTATION: A 30-year-old Han Chinese man came to us with complaint of red, painful blind right eye. He had a history of ocular trauma, retinal detachment, and two failed retinal reattachment surgeries with silicone oil left in the eye. On examination, conjunctiva congestion, band keratopathy, silicone oil emulsification, and limbus neovascularization were found. B-scan ultrasound and computed tomography scanning demonstrated retinal detachment and calcification of the eyeball wall. Histopathological analysis indicated ossification overlying the choroid. Evisceration was finally operated to relieve the pain. CONCLUSION: The retention of silicone oil in the eye probably accelerates the ossification. Timely silicone oil removal and evisceration should be recommended if necessary for phthisis bulbi.