Co-Delivery of Astaxanthin and siTGF-ß1 via Ionizable Liposome Nanoparticles for Improved Idiopathic Pulmonary Fibrosis Therapy.

Alleviating the injury of type II alveolar epithelial cells (AEC 2s) and inhibiting the activation and differentiation of fibroblasts are significant for improving the therapeutic effect of idiopathic pulmonary fibrosis (IPF). To this aim, ionizable liposome nanoparticles (ASNPs) coloaded with antioxidant drug astaxanthin (AST) and small interfering RNA targeting transforming growth factor ß1 (siTGF-ß1) were developed for enhanced IPF therapy. ASNPs showed high loading and intracellular delivery efficiency for AST and siTGF-ß1. After the injection of ASNPs in an IPF mice model, the loaded AST largely scavenged reactive oxygen species (ROS) in the diseased lung to reduce AEC2 apoptosis, thereby ensuring the integrity of the alveolar epithelium. Meanwhile, siTGF-ß1, delivered by ASNPs, significantly silenced the expression of TGF-ß1 in fibroblasts, inhibiting the differentiation of fibroblasts into myofibroblasts as well as reducing the excessive deposition of extracellular matrix (ECM). The combined use of the two drugs exhibited an excellent synergistic antifibrotic effect and was conducive to minimizing alveolar epithelial damage. This work provides a codelivery strategy of AST and siTGF-ß1, which shows great promise for the treatment of IPF by simultaneously reducing alveolar epithelial damage and inhibiting fibroblast activation.

Coaxial 3D printing of hierarchical structured hydrogel scaffolds for on-demand repair of spinal cord injury.

After spinal cord injury (SCI), endogenous neural stem cells (NSCs) near the damaged site are activated, but few NSCs migrate to the injury epicenter and differentiate into neurons because of the harsh microenvironment. It has demonstrated that implantation of hydrogel scaffold loaded with multiple cues can enhance the function of endogenous NSCs. However, programming different cues on request remains a great challenge. Herein, a time-programmed linear hierarchical structure scaffold is developed for spinal cord injury recovery. The scaffold is obtained through coaxial 3D printing by encapsulating a dual-network hydrogel (composed of hyaluronic acid derivatives and N-cadherin modified sodium alginate, inner layer) into a temperature responsive gelatin/cellulose nanofiber hydrogel (Gel/CNF, outer layer). The reactive species scavenger, metalloporphyrin, loaded in the outer layer is released rapidly by the degradation of Gel/CNF, inhibiting the initial oxidative stress at lesion site to protect endogenous NSCs; while the inner hydrogel with appropriate mechanical support, linear topology structure and bioactive cues facilitates the migration and neuronal differentiation of NSCs at the later stage of SCI treatment, thereby promoting motor functional restorations in SCI rats. This study offers an innovative strategy for fabrication of multifunctional nerve regeneration scaffold, which has potential for clinical treatment of SCI. STATEMENT OF SIGNIFICANCE: Two major challenges facing the recovery from spinal cord injury (SCI) are the low viability of endogenous neural stem cells (NSCs) within the damaged microenvironment, as well as the difficulty of neuronal regeneration at the injured site. To address these issues, a spinal cord-like coaxial scaffold was fabricated with free radical scavenging agent metalloporphyrin Mn (III) tetrakis (4-benzoic acid) porphyrin and chemokine N-cadherin. The scaffold was constructed by 3D bioprinting for time-programmed protection and modulation of NSCs to effectively repair SCI. This 3D coaxially bioprinted biomimetic construct enables multi-factor on-demand repair and may be a promising therapeutic strategy for SCI.

Infectious mononucleosis in children and differences in biomarker levels and other features between disease caused by Epstein-Barr virus and other pathogens: a single-center retrospective study in China.

Background: Infectious mononucleosis (IM) is a common viral infection that typically presents with fever, pharyngitis and cervical lymphadenopathy. Our aim was to identify the different pathogens causing IM in children admitted to our hospital and to analyze the differences in features of infection with different organisms. Methods: We retrospectively analyzed the data of children aged 0-17 years admitted to Wuhan Children's Hospital during 2013-2022 with IM. We compared symptoms, physical findings, blood counts, and serum biomarkers between patients with IM due to Epstein-Barr virus (EBV) and IM due to other pathogens. Results: Among 1480 enrolled children, 1253 (84.66%) had EBV infection, 806 (54.46%) had M. pneumoniae infection, 796 (53.78%) had cytomegalovirus infection, 159 (10.74%) had parvovirus infection, 38 (2.57%) had influenza virus infection, and 25 (1.69%) had adenovirus infection. Receiver operating characteristic curves were used to determine the area under the curve for alanine transaminase (ALT), aspartate transaminase (AST), Alkaline phosphatase (ALP), total bilirubin (TBil), indirect bilirubin (IBil) levels to assess liver damage, and for creatine kinase (CK), CK-MB, and lactate dehydrogenase (LDH) levels to assess myocardial damage. The optimal cutoff values of these biomarkers were then determined. In multivariate analysis, elevated ALT, AST, ALP, TBil, and IBil were independently associated with liver damage, and age <3 years, CK, CK-MB, and LDH with myocardial damage. Conclusion: Evaluation of biomarkers and pathogen detection may help physicians to take preventive actions to avoid serious complications in children with infectious mononucleosis.

Inhibited astrocytic differentiation in neural stem cell-laden 3D bioprinted conductive composite hydrogel scaffolds for repair of spinal cord injury.

The emergence of three-dimensional (3D) bioprinting technology has attracted ever-increasing attention in engineered tissue fabrication for stem cell-based tissue repair. However, the in vivo performance of transplanted stem cells in the tissue engineering scaffolds is still a major concern for regenerative medicine researches. Especially for neural stem cell (NSC) transplantation, the uncontrollable differentiation of the NSCs in host often leads to a poor therapeutic effect in nerve tissue repair, such as spinal cord injury (SCI) repair. To address this issue, we have fabricated a conductive composite hydrogel (CCH) scaffold loading with NSCs by 3D bioprinting, for delivering the NSCs to injured spinal cord and repairing the propriospinal nerve circuit. In our strategy, a novel conductive polymer (PEDOT:CSMA,TA) was synthesized and introduced into a photocrosslinkable gelatin/polyethylene glycol physical-gel matrix, thereby forming a composite bioink with well shear-thinning and self-healing properties. The composite bioink we prepared was then printed into the NSC-laden CCH scaffold with high shape fidelity and similar physicochemical properties to native spinal cord tissues. The NSCs encapsulated in the bioprinted CCH scaffold extended their neurites to form superior physical contact with the neighboring cells as well as the electroconductive matrix, and maintained a predominant in vivo neuronal differentiation, accompanying with few astrocytic production in the lesion area after transplantation into the SCI sites. As a result, the removal of glial scar tissues and the regeneration of well-developed nerve fibres sequentially happened, which not only facilitated nerve tissue development, but also accelerated locomotor function recovery in the SCI rats. By exploring the application of conductive biomaterials in stem cell-based SCI therapy, this work represents a feasible, new approach to precisely construct tissue engineering scaffolds for stem cell-based therapy in traumatic SCI and other nervous system diseases.

ROS-Responsive Janus Au/Mesoporous Silica Core/Shell Nanoparticles for Drug Delivery and Long-Term CT Imaging Tracking of MSCs in Pulmonary Fibrosis Treatment.

Mesenchymal stem cell (MSC) therapy has been proven to be a potentially effective approach for idiopathic pulmonary fibrosis (IPF) treatment. However, this strategy is currently limited by the poor curative effect and an insufficient comprehension of the in vivo condition of the transplanted MSCs in the remedy of IPF. To address these issues, herein, a nanosystem composed of Janus Au/mesoporous silica core/shell nanoparticles (Janus NPs) is designed for effective therapeutic and real-time tracing of MSCs in MSC-based IPF therapy. The Janus NPs consist of a Au core and a pirfenidone (PFD)-loaded mesoporous silica shell asymmetrically decorated with two targeting moieties: one is reactive oxygen species (ROS)-sensitive thioketal grafted methoxy poly(ethylene glycol) (mPEG-TK), and the other is 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE). The asymmetric decoration on each side of the particle allows long-term anchoring of the Janus NPs on the cell membrane to facilitate the responsive release of PFD in the ROS environment of the fibrotic lung, thereby enhancing the therapeutic efficacy of the transplanted MSCs by improving the microenvironment. Following drug release, the Janus NPs quickly enter into MSCs, achieving long-term computed tomography (CT) imaging tracing of MSCs in IPF model mice for an in-depth comprehension of the cell therapy mechanism. Overall, this work reports on Janus Au/PFD-loaded mesoporous silica core/shell NPs that combine the drug delivery and imaging tracking of MSCs, which may provide a strategy for the stem cell-based treatment of IPF.

Clinical analysis of 96 patients with intraorbital foreign bodies: A 10-year retrospective study.

Introduction: To investigate the clinical manifestations, diagnosis, and surgical treatment of intraorbital foreign bodies (IOFBs). Methods: Patients with IOFBs were enrolled from Wuhan Union Hospital between January 2011 and January 2021. Demographic and clinical information was extracted, including gender, age, cause and entrance of the trauma, material, size and quantity of foreign body, visual function, ocular complications, imaging findings, and surgical intervention. The patients were divided into two groups according to the timeline, group A (from January 2011 to December 2015, n = 39) and group B (from January 2016 to January 2021, n = 57). Results: The 96 patients (81 men and 15 women) were enrolled in this series, with a median age of 39.5 (1.6-76.0) years. Work-related injuries were the cause of IOFBs in 45 individuals (46.9%). Three patients (3.3%) presented severe visual impairment, and 39 patients (42.4%) presented blindness. The majority of foreign bodies were metal (44.8%), followed by wood (26.0%). Computed tomography (CT) and magnetic resonance imaging (MRI) were performed, respectively, on 89 (92.7%) and 21 (21.9%) patients with IOFBs, in which the detection rate was 80.9% for CT and 81.0% for MRI. Among the 25 patients with intraorbital wooden foreign bodies (IOWFBs), the utilization and detection rates of MRI were 50.0% and 40.0% in group A, and 93.3% and 92.9% in group B, with significant differences in both rates between the two groups (both P < 0.05). The IOWFBs detection rate in MRI was significantly higher than that in CT (78.9% vs. 45.8% overall and 92.9% vs. 53.5% in group B). The detection rates of IOFBs and IOWFBs in initial surgery were statistically different between the two groups, of which the rates were 84.6% and 40.0% in group A and 98.2% and 93.3% in group B. The reoperation rate of IOWFBs in group B (20.0%) was significantly lower than that in group A (70.0%). Conclusion: IOFBs were mainly caused by work-related injuries and might lead to serious visual impairment. The application and detectability of MRI in IOWFBs improved in recent years, and MRI presented better detectability than CT in diagnosing IOWFBs. Thus, MRI should be recommended despite negative CT findings.

Risk prediction of dysthyroid optic neuropathy based on CT imaging features combined the bony orbit with the soft tissue structures.

Purpose: To analyze computed tomographic (CT) imaging features of patients with dysthyroid optic neuropathy (DON) retrospectively and deduce a more appropriate predictive model. Methods: The CT scans and medical records of 60 patients with clinically proven Graves' ophthalmopathy (GO) with (26 women and 10 men) and without DON (16 women and 8 men) were retrospectively reviewed, and 20 age- and sex-matched control participants (12 women and 8 men) were enrolled consecutively. The bony orbit [orbital rim angle (ORA), medial and lateral orbital wall angles (MWA and LWA), orbital apex angle (OAA), and length of the lateral orbital wall (LWL)], and the soft tissue structures [maximum extraocular muscle diameters (Max EOMD), muscle diameter index (MDI), medial and lateral rectus bulk from inter-zygomatic line (MRIZL and LRIZL), proptosis, intraorbital optic nerve stretching length (IONSL), superior ophthalmic vein diameter (SOVD), apical crowding, and presence of intracranial fat prolapse] were assessed on a clinical workstation. The CT features among groups were compared, and a multivariate logistic regression analysis was performed to evaluate the predictive features of DON. Results: All bony orbital angle indicators, except ORA (p = 0.461), were statistically different among the three groups (all p < 0.05). The values of MWA, LWA, OAA, and LWL were larger in the orbits with the DON group than in the orbits without the DON group (all p < 0.05). The MDI, MRIZL, proptosis, IONSL, and SOVD were statistically significantly different among the three groups (all p < 0.05), in which the orbits with the DON group were significantly higher than the orbits without the DON group and control group. The apical crowding was more severe in the orbits with the DON group than in the orbits without the DON group (p = 0.000). There were no significant differences in the LRIZL and the presence of intracranial fat prolapse (all p > 0.05). The multivariate regression analysis showed that the MWA, MDI, and SOVD were the independent factors predictive of DON. The sensitivity and specificity for the presence of DON by combining these three indicators were 89 and 83%, respectively. Conclusion: Bone and soft tissue CT features are useful in the risk prediction of DON, especially the MWA, MDI, and SOVD were the independent factors predictive of DON.

Functional Au nanoparticles for engineering and long-term CT imaging tracking of mesenchymal stem cells in idiopathic pulmonary fibrosis treatment.

Idiopathic pulmonary fibrosis (IPF) therapy has always been a big and long-standing challenge in clinical practice due to the lack of miraculous medicine. Mesenchymal stem cells (MSCs)-based therapy has recently emerged as a promising candidate for redefining IPF therapy. Enhancing the therapeutic efficacy of MSCs and understanding of their growth, migration and differentiation in harsh lung microenviroments are two keys to improving the stem cell-based IPF treatment. Herein, a non-viral dual-functional nanocarrier is fabricated by a one-pot approach, using protamine sulfate stabilized Au nanoparticles (AuPS), to genetically engineer MSCs for simultaneous IPF treatment and monitoring the biological behavior of the MSCs. AuPS exhibits superior cellular uptake ability, which results in efficient genetic engineering of MSCs to overexpress hepatocyte growth factor for enhanced IPF therapy. In parallel, the intracellular accumulation of AuPS improves the CT imaging contrast of MSCs, allowing visual tracking of the therapeutic engineered MSCs up to 48 days. Overall, this work has described for the first time a novel strategy for enhanced therapeutic efficacy and long-term CT imaging tracking of transplanted MSCs in IPF therapy, providing great prospect for stem cell therapy of lung disease.

Chromatic visual evoked potentials identify optic nerve dysfunction in patients with Graves' orbitopathy.

PURPOSE: To explore visual dysfunction in Graves' orbitopathy (GO) objectively by analyzing chromatic visual evoked potentials (cVEP) and evaluate its diagnostic efficiency for dysthyroid optic neuropathy (DON). METHODS: In this cross-sectional study, we analyzed pattern-reversal VEP (pVEP), red-green (R-G) and blue-yellow (B-Y) cVEP in 93 subjects (21 with DON, Group A, 30 with GO, Group B, and 42 healthy controls, Group C) at Wuhan Union Hospital, China. RESULTS: Compared with Group C, the amplitudes of B-Y cVEP were significantly lower in Group B, whereas all amplitudes of cVEP, latencies and amplitudes of pVEP in Group A were significantly impaired. In addition, the pVEP latency at 60 arcmin (60'), pVEP amplitudes and R-G cVEP amplitudes were significantly different between Group A and B. Moreover, 60'cVEP R-G negative-positive (N-P) amplitude was correlated with crowding index (P = 0.001), the average thickness of ganglion cell layer and inner plexiform layer (P = 0.004). Furthermore, combination of 60'cVEP R-G amplitude and 60'pVEP P100 latency had better diagnostic efficiency than each single parameter, with optimal cut-off values of 14.20 µV and 110.65 ms, respectively. CONCLUSION: GO may induce electrophysiological changes. The presence of B-Y cVEP anomalies in moderate to severe GO patients may be an early sign of preclinical DON. A decline in 60'cVEP R-G amplitude is associated with apical crowding and thinner inner intra-retinal layers. The combination of 60'cVEP R-G N-P amplitude and 60'pVEP latency can be a useful diagnostic index for DON.

In vivo confocal microscopy assessment of meibomian glands microstructure in patients with Graves' orbitopathy.

BACKGROUND: To evaluate microstructural changes in the meibomian glands (MGs) in patients with active and inactive Graves' orbitopathy (GO), using in vivo confocal microscopy (IVCM), and to investigate the correlations between clinical and confocal findings. METHODS: Forty patients (80 eyes) with GO (34 eyes with active GO, 46 eyes with inactive GO), and 31 age- and sex-matched control participants (62 eyes) were enrolled consecutively. A researcher recorded the clinical activity score (CAS) for each patient. A complete ophthalmic examination was then performed, including external eye, ocular surface and MGs. IVCM of the MGs was performed to determine the MG acinar density (MAD), MG longest and shortest diameters (MALD and MASD), MG orifice area (MOA), MG acinar irregularity (MAI), meibum secretion reflectivity (MSR), acinar wall inhomogeneity (AWI), acinar periglandular interstices inhomogeneity (API), and severity of MG fibrosis (MF). RESULTS: All confocal microscopy assessments of MGs significantly differed among groups (all P = 0.000). Compared to controls, GO groups showed lower MOA (1985.82 ± 1325.30 µm2 in active GO and 2021.59 ± 1367.45 µm2 in inactive GO vs. 3896.63 ± 891.90 µm2 in controls, all P = 0.000) and MAD (87.21 ± 32.69 /mm2 in active GO and 80.72 ± 35.54 /mm2 in inactive GO vs. 114.69 ± 34.90 /mm2 in controls, P = 0.001 and 0.000, respectively); greater MALD (118.11 ± 30.23 µm in active GO and 120.58 ± 27.64 µm in inactive GO vs. 58.68 ± 20.28 µm in controls, all P = 0.000) and MASD (44.77 ± 19.16 µm in active GO and 46.02 ± 20.70 µm in inactive GO vs. 27.80 ± 9.90 µm in controls, all P = 0.000); and higher degrees of MAI, MSR, and MF (all P<0.05). Eyes with active GO had higher degrees of MAI (P = 0.015), AWI (P = 0.000), and API (P = 0.000), while eyes with inactive GO had higher degrees of MSR (P = 0.000) and MF (P = 0.017). In GO groups, AWI and API were positively correlated with CAS (r = 0.640, P = 0.000; r = 0.683, P = 0.000, respectively), and MF was negatively correlated with CAS (r = - 0.228, P = 0.042). CONCLUSIONS: IVCM effectively revealed microstructural changes of MGs in eyes with GO and provided strong in vivo evidence for the roles of obstruction and inflammation in the ocular surface disease process. Furthermore, it revealed discernible patterns of MG abnormalities in eyes with active GO and inactive GO, which are not easily distinguishable by typical clinical examinations.

Retinal nerve fiber layer thickness measured by optical coherence tomography predicts visual recovery after orbital decompression for dysthyroid optic neuropathy.

PURPOSE: To determine the prognostic value of optical coherence tomography (OCT) measurement of the peripapillary retinal nerve fiber layer (RNFL) thickness in visual recovery after orbital decompression of patients with dysthyroid optic neuropathy (DON). METHODS: A total of 52 eyes of 37 patients who underwent orbital decompression for DON between 2013 and 2019 were retrospectively reviewed. We examined peripapillary RNFL thickness, best-corrected visual acuity (BCVA), visual field (VF) for mean deviation (MD) and pattern standard deviation (PSD), and pattern-reversed visual evoked potential (PVEP) for P100 latency and amplitude before and after surgery. Black and white checkerboard square sizes of PVEP were 15 and 60 arcmin (arcminute and minute of angle). Changes in RNFL overall thickness and by quadrant and interocular differences were evaluated and studied regarding changes in BCVA, VF and PVEP. RESULTS: There was a significant improvement in BCVA, VF, and PVEP, whereas a dramatic reduction in RNFL thickness of all DON patients in global average, temporal, superior, and inferior quadrants (P = 0.005, P = 0.024, P = 0.016, and P = 0.001, respectively) after decompression surgery, except for nasal quadrant (P = 0.057). The preoperative RNFL thickness in each quadrant was negatively correlated with postoperative changes of BCVA and PSD and positively correlated with changes of MD and P100 amplitude at 60 arcmin (all P < 0.05). Except for temporal quadrant (P = 0.125), the preoperative RNFL thickness in other quadrants was positively correlated with postoperative changes of P100 amplitude at 15 arcmin (all P < 0.05). The nasal RNFL thickness was an excellent predictor for improvement in BCVA by 20/25 or better and in MD by 10 dB or more after surgery, whose cutoff value was 73.50 µm, while the inferior and superior RNFL thickness could act as a predictor for improvement in P100 amplitude by 5 µV or more at 60 arcmin and at 15 arcmin, respectively, whose cutoff value was, respectively, 143.00 µm and 130.50 µm (all P < 0.05). CONCLUSION: RNFL thickness measured by OCT was correlated with visual function recovery after decompression surgery in patients with DON, which could also act as a predictor for better visual prognosis.

Comparison of 2-wall versus 3-wall orbital decompression against dysthyroid optic neuropathy in visual function: A retrospective study in a Chinese population.

ABSTRACT: To compare visual function of 2-wall (medial and lateral) versus 3-wall (medial, lateral, and inferior) orbital decompression in patients with dysthyroid optic neuropathy (DON).A total of 52 eyes of 37 patients underwent orbital decompression for DON between 2013 and 2019 were retrospectively reviewed. Two- or 3-wall decompression was performed in 31 eyes of 23 patients and 21 eyes of 14 patients, respectively. We examined best-corrected visual acuity (BCVA), visual field mean deviation (MD) and pattern standard deviation (PSD), pattern-reversed visual evoked potential (PVEP) for P100 latency and amplitude at 60 and 15 arcmin stimulation checkerboard size, as well as proptosis using Hertel exophthalmometry.Whether 2-wall or 3-wall decompression, all parameters of visual function were improved after surgery (all P < .05). The improvement in BCVA, MD, and PSD was not statistically significant between groups (all P > .05). Proptosis reduction was higher after 3-wall decompression (P = .011). Mean increase in P100 amplitude after 3-wall decompression was statistically higher than that of after 2-wall decompression at 60 and 15 arcmin (P = .045 and .020, respectively), while the mean decrease in P100 latency was similar between the groups (P = .821 and .655, respectively). Six patients (66.67%) had persistent postoperative diplopia and 1 patient (20%) had new-onset diplopia in 3-wall decompression group, which were higher than in 2-wall decompression group (46.15% persistent postoperative diplopia and no new-onset diplopia).Both 2-wall and 3-wall decompression can effectively improve visual function of patients with DON. Three-wall decompression provides better improvement in P100 amplitude and proptosis, however new-onset diplopia is more common with this surgical technique.

Intense Pulsed Light Therapy for Patients with Meibomian Gland Dysfunction and Ocular Demodex Infestation.

To observe the clinical changes of meibomian gland dysfunctipn (MGD) and ocular Demodex infestation after intense pulsed light (IPL) treatment to further examine the mechanism of IPL treating patients with MGD and ocular Demodex infestation. The medical records of 25 patients (49 eyes) with MGD treated with IPL, were retrospectively examined to determine outcomes. Associated ocular-surface parameters (ocular surface disease index, OSDI; lipid layer thickness, LLT; noninvasive first breakup time, NIF-BUT; noninvasive average breakup time, NIAvg-BUT; tear film breakup area, TBUA; Schirmer I Test, SIT; corneal fluorescein staining, CFS), eyelid margin abnormalities, meibum quality and expressibility, MG morphological parameters (macrostructure and microstructure), and the number of Demodex infestation were examined before and after treatment. The MG microstructure and the Demodex infestation were examined via in vivo confocal microscopy (IVCM). The results showed that there were statistically significant differences in associated ocular-surface parameters (all P<0.05) before and after IPL treatment, except SIT (P=0.065). Eyelid margin abnormalities, meibum quality and expressibility obviously improved in upper and lower eyelid after IPL treatment (all P<0.0001). MG macrostructure (MG dropouts) decreased in upper (P=0.002) and lower eyelid (P=0.001) after IPL treatment. The nine parameters of MG microstructure in upper and lower eyelid all distinctly improved after IPL treatment (all P<0.0001). The mean number of Demodex mites on the upper lid margin (6.59±7.16 to 3.12±3.81/9 eyelashes) and lower lid margin (2.55±2.11 to 1.29±1.53/9 eyelashes) significantly reduced after IPL treatment (all P<0.0001). The Demodex eradication rate was 20% (8/40) in upper lid margin and 34.15% (14/41) in lower lid margin. These findings indicate that IPL shows great therapeutic potential for patients of MGD and ocular Demodex infestation.

The correlation between the microstructure of meibomian glands and ocular Demodex infestation: A retrospective case-control study in a Chinese population.

Meibomian gland dysfunction (MGD) is a common disease in ophthalmic clinic. This study aimed to explore ocular Demodex infestation on the microstructure changes of the meibomian glands (MGs) in patients with MGD by in vivo confocal microscopy (IVCM).We retrospectively reviewed 103 eyes of 52 patients with MGD and 62 eyes of 31 non-MGD patients. All enrolled patients underwent IVCM examination. The following IVCM parameters were recorded: the MG acinar density (MAD), MG acinar longest diameter (MALD), MG acinar shortest diameter (MASD), MG orifice area (MOA), severity of MG fibrosis (MF), MG acinar irregularity (MAI), meibum secretion reflectivity (MSR), inhomogeneous appearance of walls of acinar units (AWI) and periglandular interstices of acinar units (API), and the number of Demodex.The positive rate of Demodex infestation in MGDs was 89.32%, and statistically higher than control group (controls; P < .001). All parameters showed statistically significant differences between MGDs and controls (P < .001), and Demodex-negative group and Demodex-positive group (P < .05) in both MGDs and controls, except MAD (P = .826) in controls. The number of Demodex was positively correlated with MALD, MASD, MF, MAI, MSR, AWI, and API in MGDs and controls (P < .05), and negatively correlated with MAD and MOA in MGDs (P < .05). MOA showed a strong significant correlation with the number of Demodex in controls (P < .001), whereas there was no significant difference between the number of Demodex and the MAD in controls (P = .448).Demodex can cause microstructural changes of MGs, which can cause or aggravate MGD, and the more the number of Demodex infestation, the more serious the structural damage.

Hydrogen sulfide inhibits epithelial-mesenchymal transition in peritoneal mesothelial cells.

Peritoneal fibrosis (PS) determines the long-term outcome of peritoneal dialysis (PD). We previous confirmed that hydrogen sulfide (H2S) inhibited PS, but its cellular mechanism was not fully elucidated. Epithelial-mesenchymal transition (EMT) of mesothelial cells (MCs) is an important cellular event of PS, we therefore investigated whether EMT can be affected by H2S in MCs. Rats were treated with 4.25% -glucose PD fluids plus lipopolysaccharide for 28 days to produce PS, and NaHS (56 µg/kg.d) was given simultaneously. NaHS (56 µg/kg.d) reduced the deposition of collagen in the submesothelial zone compared with the PS group. In primarily cultured rat MCs, 4.25% -glucose PD fluid induced EMT in MCs featured as loss of ZO-1 and Cytokeratin, and increase of α-SMA, plasminogen activator inhibitor 1, fibronectin and TGF-ß1 proteins. PD fluid also increased IL-6 and monocyte chemotactic protein-1 mRNA expressions as well as the phosphorylation of Smad2/3 and Smad3. NaHS (50-300 µmol/L) reversed the above alterations with the optimal dose at 100 µmol/L. Thus, exogenous H2S improves PS by inhibiting EMT in MCs. The anti-EMT effect of H2S is associated with the inhibition of inflammation and TGF-ß1-Smad signal pathway.