Alterations in the Ocular Surface and Corneal Subbasal Nerve Plexus Following Various Retinal Surgical Procedures: A One-Year Confocal Microscopy Prospective Study.

Purpose: To evaluate the effects of retinal surgery on the ocular surface and corneal subbasal nerve plexus (SNP). Methods: Ninety-eight patients undergoing 23-gauge pars plana vitrectomy for various vitreoretinal disorders were prospectively studied. We collected detailed operative and perioperative data, measuring dry eye syndrome (DED) severity and Ocular Surface Disease Index (OSDI) scores before surgery and at postoperative intervals. In vivo confocal microscopy (IVCM) quantified SNP and dendritic cell (DC) densities. Results: Fifty-three patients were analyzed. Post-surgery, OSDI scores rose from a baseline of 5.5 ± 3.5 to 12.24 ± 6.5 at one month, later reducing to 7.8 ± 4.0 after a year. DED severity increased from 0.6 ± 0.6 initially to 1.6 ± 0.6 at three months, returning to near baseline (0.9 ± 0.6) one year after surgery. DC densities increased notably by the third (58.85 ± 75.6 cells/mm²) and ninth (59.95 ± 86 cells/mm²) postoperative months, especially in patients undergoing combined phacoemulsification, vitrectomy, and C3F8 gas tamponade. SNP parameters, particularly nerve fiber density and length, showed significant declines one month post-surgery, not recovering to baseline levels within a year. Fiber density dropped from 19.06 ± 8.3 fibers/mm² preoperatively to 4.68 ± 4.8 fibers/mm² at one month, partially recovering to 10.64 ± 8.2 fibers/mm² at twelve months. Fiber length decreased from 13.31 ± 3.2 mm/mm² to 6.86 ± 3.4 mm/mm² at one month, later improving to 9.81 ± 4.5 mm/mm² at twelve months, notably in patients with silicone oil (SiO2) tamponade. Conclusion: Retinal surgery, especially when combined with phacoemulsification and C3F8 or SiO2 tamponade, significantly affects ocular surface integrity and SNP density, with these changes lasting up to a year. Expanded studies with more patients and longer follow-up, using finer 25- and 27-gauge vitrectomy tools, are recommended to confirm and extend these findings.

Sevoflurane acts as an antidepressant by suppression of GluN2D-containing NMDA receptors on interneurons.

BACKGROUND AND PURPOSE: Sevoflurane, a commonly used inhaled anaesthetic known for its favourable safety profile and rapid onset and offset, has not been thoroughly investigated as a potential treatment for depression. In this study, we reveal the mechanism through which sevoflurane delivers enduring antidepressant effects. EXPERIMENTAL APPROACH: To assess the antidepressant effects of sevoflurane, behavioural tests were conducted, along with in vitro and ex vivo whole-cell patch-clamp recordings, to examine the effects on GluN1-GluN2 incorporated N-methyl-d-aspartate (NMDA) receptors (NMDARs) and neuronal circuitry in the medial prefrontal cortex (mPFC). Multiple-channel electrophysiology in freely moving mice was performed to evaluate sevoflurane's effects on neuronal activity, and GluN2D knockout (grin2d-/-) mice were used to confirm the requirement of GluN2D for the antidepressant effects. KEY RESULTS: Repeated exposure to subanaesthetic doses of sevoflurane produced sustained antidepressant effects lasting up to 2 weeks. Sevoflurane preferentially inhibited GluN2C- and GluN2D-containing NMDARs, causing a reduction in interneuron activity. In contrast, sevoflurane increased action potentials (AP) firing and decreased spontaneous inhibitory postsynaptic current (sIPSC) in mPFC pyramidal neurons, demonstrating a disinhibitory effect. These effects were absent in grin2d-/- mice, and both pharmacological blockade and genetic knockout of GluN2D abolished sevoflurane's antidepressant actions, suggesting that GluN2D is essential for its antidepressant effect. CONCLUSION AND IMPLICATIONS: Sevoflurane directly targets GluN2D, leading to a specific decrease in interneuron activity and subsequent disinhibition of pyramidal neurons, which may underpin its antidepressant effects. Targeting the GluN2D subunit could hold promise as a potential therapeutic strategy for treating depression.

A Novel Simple ImmunoAssay for Quantification of Blood Anti-NMDAR1 Autoantibodies.

High titers of anti-NMDAR1 autoantibodies in human brain cause anti-NMDAR1 encephalitis, a rare disease that displays a variety of psychiatric symptoms and neurological symptoms. Currently, immunohistochemical staining and cell-based assays are the standard methods for detection and semi-quantification of the anti-NMDAR1 autoantibodies. Low titers of blood circulating anti-NMDAR1 autoantibodies have been reported in a significant subset of the general human population. However, detection and quantification of these low titers of blood circulating anti-NMDAR1 autoantibodies are problematic because of high non-specific background from less diluted serum/plasma. Development of a new method to quantify these low titers of blood anti-NMDAR1 autoantibodies is necessary to understand their potential impacts on psychiatric symptoms and cognition. Based on our previous One-Step assay, we report the development of a novel simple immunoassay to quantify cross-species blood anti-NMDAR1 autoantibodies, and its validation with immunohistochemistry and cell-based assays in both humans and mice.

Corneal Sub-Basal Nerve Plexus Regeneration Pattern following Implantable Collamer Lens Implantation for Myopia: A Prospective Longitudinal In Vivo Confocal Microscopy Study.

Implantable Collamer Lens (ICL) surgery has increasingly been adopted for myopia correction in recent decades. This study, employing in vivo confocal microscopy (IVCM), aimed to assess the impact of corneal incision during ICL surgery on the corneal sub-basal nerve plexus (SNP) and adjacent immune dendritiform cells (DCs). In this longitudinal study, eyes from 53 patients undergoing ICL surgery were assessed preoperatively and postoperatively over a twelve-month period. Quantification of seven SNP parameters was performed using ACCMetrics V.2 software. Ultimately, the final analysis was restricted to one eye from each of the 37 patients who completed a minimum of three months' postoperative follow-up. Preoperative investigations revealed a positive correlation of DC density with patient age and a negative association with corneal nerve fiber density (CNFD). Additionally, both DCs and CNFD were positively linked to spherical equivalent refraction (SER) and inversely related to axial length (AL). Intriguingly, preoperative DC density demonstrated an indirect relationship with both baseline and postoperative CNFD changes. Post-surgery, an initial surge in DC density was observed, which normalized subsequently. Meanwhile, parameters like CNFD, corneal nerve fiber length (CNFL), and corneal nerve fractal dimension (CNFrD) initially showed a decline following surgery. However, at one-year follow-up, CNFL and CNFrD displayed significant recovery, while CNFD did not return to its baseline level. This study thus delineates the regeneration pattern of SNP and alterations in DC density post-ICL surgery, highlighting that CNFD in the central cornea does not completely revert to preoperative levels within a year. Given these findings, practitioners are advised to exercise caution in older patients, those with high myopia, or elevated preoperative DCs who may undergo delayed SNP regeneration.

Retinal and Choroidal Changes Following Implantable Collamer Lens V4c Implantation in High Myopia Patients-A 1-Year Follow-Up Study.

This prospective study aimed to evaluate the impact of Visian Implantable Collamer Lens (ICL) V4c implantation on retinal and choroidal morphology in patients with high myopia. A total of 97 eyes from 52 high myopic patients who underwent ICL V4c implantation were followed up for 12 months. Preoperative and postoperative evaluations included comprehensive ophthalmic assessments and enhanced depth imaging optical coherence tomography (EDI-OCT) to analyze changes in central retinal thickness (CRT), retinal volume (CRV), choroidal thickness (ChT), total choroidal area (TCA), luminal area (LA), and choroidal vascular index (CVI). Repeated measures mixed-effects models were used for comparing pre- and postoperative measurement variables and exploring relationships among age, axial length (AL), spherical equivalent refraction (SER), and postoperative retinal and choroidal changes, with statistical significance set at p < 0.05. Follow-up assessments were conducted at various time points, with participation rates ranging from 21% to 98%. Baseline characteristics showed a median age of 26.7 years, -10.14 diopters of SER, and an AL of 27.44 mm. Throughout the 12-month follow-up, CRT and 3.0 mm CRV consistently increased compared to the baseline, with statistically significant rises observed at postoperative day 1, week 1, and month 12. Most ChT measurements, including subfoveal ChT, declined over the 12 months, except at postoperative 6 months. Horizontal and vertical TCA and LA values significantly increased throughout the follow-up, except for month 6. After surgery, both horizontal and vertical CVI parameters exhibited an increase compared to the baseline, with some changes reaching statistical significance. Correlation analysis performed by repeated measures mixed-effects models showed that no relationship was found between age, AL, and SER and changes in postoperative retinal parameters and CVI parameters. However, postoperative changes in ChT and choroidal area parameters showed a negative correlation with AL and a positive correlation with SER. Our research demonstrated that ICL V4c implantation resulted in noteworthy alterations in retinal and choroidal morphology over a 1-year follow-up period. Moreover, in patients with high myopia, individuals with longer AL and higher degrees of myopia exhibited more pronounced postoperative changes in the choroid and retina. Further studies with extended follow-up durations are necessary to comprehensively understand the long-term effects of ICL implantation on retinal and choroidal morphology and function.

Increased risk of postpartum depression in women with lactational mastitis: a cross-sectional study.

Background: A high incidence of lactational mastitis mainly occurs during the first month of breastfeeding. It may cause severe pain, frustration, fatigue, stress, and breastfeeding concerns. However, few studies investigated the effects of lactational mastitis on postpartum depression. This study investigated the potential association between lactational mastitis and postpartum depression. Methods: We examined the associations of lactational mastitis with postpartum depression in 1,551 Chinese women. Lactational mastitis was diagnosed by breast specialists. The presence of depression symptoms was evaluated by the Edinburgh Postnatal Depression Scale (EPDS) and Patient Health Questionnaire 9 (PHQ9) at 6 weeks after delivery. Multiple linear regression analysis and multivariable log-binomial regression analysis were performed to estimate the association between lactational mastitis and postpartum depression. Results: Among the 1,551 mothers, 147 (9.5%) experienced lactational mastitis diagnosed by breast specialists during the postpartum period. Compared with women without lactational mastitis, the proportion of women with depression symptoms was significantly higher (38.1% vs. 27.4%, p = 0.008), and the risk of postpartum depression increased by 68% (RR = 1.68, 95% CI, 1.18, 2.40) in women who had experienced lactational mastitis. In addition, the risk of self-harm or suicidal ideation increased by 89% (RR = 1.89, 95% CI, 1.08, 3.29) in women who experienced lactational mastitis. In stratified analysis, the associations of lactational mastitis with postpartum depression appeared stronger among women aged ≥35 years, with maternal comorbidities, and who delivered a female neonate. Conclusion: The study results suggest that lactational mastitis is a risk factor for depression during the postpartum period. The impact of lactational mastitis on maternal mental health requires further attention. Clinical trial registration: chictr.org.cn, ChiCTR2000041519.

Metabolomic Profiling of Aqueous Humor from Pathological Myopia Patients with Choroidal Neovascularization.

Choroidal neovascularization (CNV) is a severe complication observed in individuals with pathological myopia (PM). Our hypothesis is that specific metabolic alterations occur during the development of CNV in patients with PM. To investigate this, an untargeted metabolomics analysis was conducted using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) on aqueous humor (AH) samples obtained from meticulously matched PM patients, including those with CNV (n = 11) and without CNV (n = 11). The analysis aimed to identify differentially expressed metabolites between the two groups. Furthermore, the discriminative ability of each metabolite was evaluated using the area under the receiver operating characteristic curve (AUC). Enriched metabolic pathways were determined using the KEGG and MetaboAnalyst databases. Our results revealed the detection of 272 metabolites using GC-MS and 1457 metabolites using LC-MS in AH samples. Among them, 97 metabolites exhibited significant differential expression between the CNV and non-CNV groups. Noteworthy candidates, including D-citramalic acid, biphenyl, and isoleucylproline, demonstrated high AUC values ranging from 0.801 to 1, indicating their potential as disease biomarkers. Additionally, all three metabolites showed a strong association with retinal cystoid edema in CNV patients. Furthermore, the study identified 12 altered metabolic pathways, with five of them related to carbohydrate metabolism, suggesting their involvement in the occurrence of myopic CNV. These findings provide possible disease-specific biomarkers of CNV in PM and suggest the role of disturbed carbohydrate metabolism in its pathogenesis. Larger studies are needed to validate these findings.

Preventive and Therapeutic Autoantibodies Protect against Neuronal Excitotoxicity.

High titers of anti-NMDAR1 IgG autoantibodies were found in the brains of patients with anti-NMDAR1 encephalitis that exhibits psychosis, impaired memory, and many other psychiatric symptoms in addition to neurological symptoms. Low titers of blood circulating anti-NMDAR1 IgG autoantibodies are sufficient to robustly impair spatial working memory in mice with intact blood-brain barriers (BBB). On the other hand, anti-NMDAR1 autoantibodies were reported to protect against neuronal excitotoxicity caused by excessive glutamate in neurological diseases. Activation of extrasynaptic NMDARs is responsible for neuronal excitotoxicity, whereas activation of synaptic NMDARs within the synaptic cleft is pro-survival and essential for NMDAR-mediated neurotransmission. Unlike small IgG, IgM antibodies are large and pentameric (diameter of ~30 nm). It is plausible that IgM anti-NMDAR1 autoantibodies may be restricted to bind extrasynaptic NMDARs and thereby specifically inhibit neuronal excitotoxicity, but physically too large to enter the synaptic cleft (width: 20-30 nm) to suppress synaptic NMDAR-mediated neurotransmission in modulation of cognitive function and neuronal pro-survival signaling. Hence, blood circulating anti-NMDAR1 IgM autoantibodies are both neuroprotective and pro-cognitive, whereas blood circulating anti-NMDAR1 IgG and IgA autoantibodies are detrimental to cognitive function. Investigation of anti-NMDAR1 IgM autoantibodies may open up a new avenue for the development of long-lasting preventive and therapeutic IgM anti-NMDAR1 autoantibodies that protect from neuronal excitotoxicity in many neurological diseases and psychiatric disorders.

Effect of 50-Hertz Sinusoidal Vibration on the Uterus in Ovariectomy-Induced Osteoporotic Rats.

Objective: To evaluate the influence of sinusoidal vibration (50-Hertz) stimulation on the uterus of osteoporotic rats. Methods: We constructed an osteoporosis rat model by ovariectomy (OVX). 36 3-month-old Sprague Dawley rats were randomly divided into the control group, vibrating group, sham operation group, sham operation vibrating group, OVX group, and OVX vibrating group (n = 6 per group). Rats started to vibrate one week after the operation: one 10 minutes 50-Hertz sinusoidal vibration per day, except for Saturday and Sunday. In the second, 8, and 12 week after vibration stimulation, rats were sacrificed in batches. And then, the uteruses were taken out to measure the wet weight and calculate uterus relative wet weight. Results: Compared with the control group, OVA induced a significant increase in wet weight and relative wet weight in rat uterus. The vibration was to the uterus wet weight and the uterus relative wet weight in ovariectomized rats and at the same time had no significant effect, but the 12-week prolonged vibration can significantly reduce the uterus wet weight and the uterus relative wet weight in ovariectomized rats than 2 weeks. Conclusions: The uterus wet weight and the uterus relative wet weight were increased in the OVA-induced osteoporosis rats. The 50-Hertz sinusoidal vibration had no significant effect on the uterus wet weight and the uterus relative wet weight in the ovariectomized rats at the same time, but 12 weeks of vibration can significantly reduce the uterine wet weight and uterine relative wet weight of ovariectomized rats. And the uterus relative wet weight can be used as a new indicator of stimulating the uterus.

Optical Coherence Tomography Benefits the Diagnosis and Follow-Up of Primary Central Nervous System Lymphoma with Intraocular Involvement.

Purpose: To describe the characteristic manifestations of vitreoretinal lymphoma (VRL) with optical coherence tomography (OCT) and monitor their outcomes after treatmEnt. Patients and Methods: Patients with primary central nervous system lymphoma (PCNSL) and intraocular involvement were assigned to the VRL group. OCT manifestations were analyzed and changes in abnormalities were recorded after intravitreal methotrexate injections. OCT manifestations of PCNSL patients without intraocular involvement were analyzed as well (non-VRL group). Results: There were 48 eyes with high-quality OCT records in the VRL group, of which 19 had abnormal manifestations. The most frequent abnormality was outer retina (OR) fuzzy borders (14 of 19, 73.7%). Other abnormalities included: focal subretinal deposits (8 of 19, 42.1%), hyperreflective subretinal dots (2 of 19, 10.5%), pigment epithelium detachment (PED) (5 of 19, 26.3%), preretinal deposits (5 of 19, 26.3%), epiretinal membrane (3 of 19, 15.8%), cystoid macular edema (3 of 19, 15.8%), subretinal fluid (3 of 19, 15.8%), outer retina atrophy (2 of 19, 10.5%), unilateral optic papilledema (2 of 19, 10.5%), retinal thickening (1 of 19, 5.3%), and subretinal fibrosis (1 of 19, 5.3%). Nine eyes with retinal abnormalities were receiving regular intravitreal methotrexate. The retinal structure of seven eyes (only outer retina involved) returned to almost normal on OCT images. The remaining two eyes (with severe retinal vasculitis) showed little improvement after treatment. Conclusion: OCT is helpful for the diagnosis of PCNSL with intraocular involvement and long-term follow-up of the disease. Summary Statement: The characteristic manifestations of vitreoretinal lymphoma (VRL) with optical coherence tomography (OCT) were described and their outcomes after treatment were monitored. These findings suggested that OCT is helpful for the diagnosis of PCNSL with intraocular involvement and long-term follow-up of the disease.

Comparison of Prophylactic Norepinephrine and Phenylephrine Infusions During Spinal Anaesthesia for Primary Caesarean Delivery in Twin Pregnancies: A Randomized Double-Blinded Clinical Study.

Background: Norepinephrine has been associated with improved heart rate (HR) and cardiac output (CO) compared to phenylephrine as a treatment for post-spinal hypotension during caesarean delivery (CD) in singleton pregnancies. Our current study compared the effects of norepinephrine and phenylephrine in maintaining maternal hemodynamics after spinal anaesthesia in twin pregnancies during elective CD. Methods: This was a double-blinded, randomized, controlled study. From December 2017 to December 2018, 62 women with healthy twin term pregnancies undergoing elective CD under spinal anaesthesia were studied. Following spinal induction, either norepinephrine (6 µg/mL) or phenylepinephrine (75 µg/mL) was infused at 60 mL/h to maintain systolic blood pressure (SBP) near baseline until delivery. HR, SBP, systemic vascular resistance (SVR), and CO were collected using anaesthesia monitors and continuous-pulse waveform analysis. The primary outcome was maternal CO. Other parameters of maternal hemodynamics, umbilical cord blood gases, and adverse events were also compared. Results: Hemodynamic variables (CO, SBP, HR, and SVR) between spinal anaesthesia induction to skin incision were similar between the two groups (P = 0.889, 0.057, 0.977, and 0.416, respectively). The incidence of bradycardia was significantly higher in the phenylephrine group (69%) than in the norepinephrine group (24.2%, P<0.001). Maternal nausea and vomiting, hypotension, reactive hypertension, and neonatal outcomes did not differ between the groups. Conclusion: When administered as a prophylactic fixed-rate infusion, phenylephrine and norepinephrine are both capable of maintaining maternal blood pressure following spinal anaesthesia in twin pregnancies. There were no differences in the maternal hemodynamics or foetal outcomes between women receiving norepinephrine and phenylephrine. Previous Presentations: Presented at the 51st Society for Obstetric Anesthesia and Perinatology Annual Meeting, Phoenix, Arizona, May 1-5, 2019. Clinical Trial Number and Registry: No. ChiCTR-IOR-17013358.

Over-representation of potential SP4 target genes within schizophrenia-risk genes.

Reduction of Sp4 expression causes age-dependent hippocampal vacuolization and many other intermediate phenotypes of schizophrenia in Sp4 hypomorphic mice. Recent human genetic studies from both the Schizophrenia Exome Sequencing Meta-Analysis (SCHEMA) and the Genome-Wide Association Study (GWAS) validated SP4 as a schizophrenia-risk gene over the exome-wide or the genome-wide significance. Truncation of the human SP4 gene has an odds ratio of 9.37 (3.38-29.7) for schizophrenia. Despite successful identification of many schizophrenia-risk genes, it is unknown whether and how these risk genes may interact with each other in the development of schizophrenia. By taking advantage of the specific localization of the GC-boxes bound by SP4 transcription factors, I analyzed the relative abundance of these GC-boxes in the proximal promoter regions of schizophrenia-risk genes. I found that the GC-box containing genes are significantly over-represented within schizophrenia-risk genes, suggesting that SP4 is not only a high-risk gene for schizophrenia, but may also act as a hub of network in the regulation of many other schizophrenia-risk genes via these GC-boxes in the pathogenesis of schizophrenia.

Chronic presence of blood circulating anti-NMDAR1 autoantibodies impairs cognitive function in mice.

High titers of anti-NMDAR1 autoantibodies in brain cause anti-NMDAR1 encephalitis that displays psychiatric symptoms of schizophrenia and/or other psychiatric disorders in addition to neurological symptoms. Low titers of anti-NMDAR1 autoantibodies are reported in the blood of a subset of the general human population and psychiatric patients. Since ~0.1-0.2% of blood circulating antibodies cross the blood-brain barriers and antibodies can persist for months and years in human blood, it is important to investigate whether chronic presence of these blood circulating anti-NMDAR1 autoantibodies may impair human cognitive functions and contribute to the development of psychiatric symptoms. Here, we generated mice carrying low titers of anti-NMDAR1 autoantibodies in blood against a single antigenic epitope of mouse NMDAR1. Mice carrying the anti-NMDAR1 autoantibodies are healthy and display no differences in locomotion, sensorimotor gating, and contextual memory compared to controls. Chronic presence of the blood circulating anti-NMDAR1 autoantibodies, however, is sufficient to impair T-maze spontaneous alternation in the integrity of blood-brain barriers across all 3 independent mouse cohorts, indicating a robust cognitive deficit in spatial working memory and/or novelty detection. Our studies implicate that chronic presence of low titers of blood circulating anti-NMDAR1 autoantibodies may impair cognitive functions in both the general healthy human population and psychiatric patients.

Cognitive Impact by Blood Circulating Anti-NMDAR1 Autoantibodies.

Antibodies persist months and years in blood. Chronic presence of low titers of blood circulating anti-NMDAR1 autoantibodies are sufficient to impair cognitive function in the integrity of the BBB in mice, suggesting potential cognitive damaging effects of low titers of blood circulating anti-NMDAR1 autoantibodies in the general human population and psychiatric patients. Investigation of anti-NMDAR1 autoantibodies against individual NMDAR1 antigenic epitopes may potentially provide risk biomarkers and therapeutic targets for development of immunotherapy as a precision medicine for psychiatric patients in the future.

A novel one-step quick assay for detection of SARS-COV2 antibodies across mammalian species.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has so far infected almost a hundred of millions of people and caused more than a million of death across the world. Many serological tests have been developed to track down virus infection in community via identification of antibodies against SARS-CoV2 virus. However, the tests vary in sensitivity, specificity, complexity, and speed. Here, I developed a simple, one-step, quick test to detect antibodies against SARS-CoV2 N (scN) nucleocapsid protein via direct visualization of antigen-antibody reaction. A total of 40 serum samples of SARS-CoV2 patients were purchased from RayBiotech. A total of 50 pre-pandemic human serum samples from San Diego Blood Bank were used as negative controls. After performing the one-step quick test of these 90 serum samples, I found that 39 samples are positive for anti-scN antibodies. All of the 39 positives are from the 40 SARS-CoV2 patients, suggesting that the one-step test is more sensitive than the lateral flow immunoassay (LFIA), the most widely used rapid antibody test. None of the 50 pre-pandemic samples is positive for anti-scN antibodies, indicating that the one-step test has an excellent specificity. The one-step test takes only ~5 min to detect the antibodies; and 1 ml of Escherichia coli culture can produce reagent proteins sufficient for thousands of the tests. Since the one-step test does not need a secondary antibody, it can be used as a universal test for anti-scN antibodies across different mammalian species to track down both human infection and the animal reservoir of SARS-CoV2 virus.

Clinical Relevance of the High Prevalence of MYD88 L265P Mutated Vitreoretinal Lymphoma Identified by Droplet Digital Polymerase Chain Reaction.

Purpose: To investigate the frequency and clinical relevance of missense mutation at position 265 changing leucine to proline in the myeloid differentiation factor 88 gene (MYD88 L265P) in the vitreous of Chinese patients with vitreoretinal lymphoma (VRL) using droplet digital polymerase chain reaction (ddPCR).Methods: Vitreous fluid (VF) from 29 eyes of 20 VRL patients at the North Huashan Hospital were included. MYD88 L265P analysis of VF was performed using ddPCR. Associations between clinicopathologic characteristics and MYD88 mutation were analyzed using t-test or Fisher's exact test.Results: MYD88 L265P mutations were detected in 22 of 29 samples from 14 patients with diffuse large B-cell lymphomas and one patient with lymphoplasmacytoid lymphoma. However, no significant associations were found between MYD88 L265P mutation status and age, sex, lymphoma subtype or location of the primary lesion.Conclusion: The high prevalence of MYD88 L265P identified by ddPCR suggests that this method of evaluating the frequency of MYD88 L265P is a promising tool for accurate diagnosis of VRL.

Chronic nicotine, but not suramin or resveratrol, partially remediates the mania-like profile of dopamine transporter knockdown mice.

Bipolar disorder (BD) is a severe mental illness affecting 2% of the global population. Current pharmacotherapies provide incomplete symptom remediation, highlighting the need for novel therapeutics. BD is characterized by fluctuations between mania and depression, likely driven by shifts between hyperdopaminergia and hypercholinergia, respectively. Hyperdopaminergia may result from insufficient activity of the dopamine transporter (DAT), the primary mediator of synaptic dopamine clearance. The DAT knockdown (DAT KD) mouse recreates this mechanism and exhibits a highly reproducible hyperexploratory profile in the cross-species translatable Behavioral Pattern Monitor (BPM) that is: (a) consistent with that observed in BD mania patients; and (b) partially normalized by chronic lithium and valproate treatment. The DAT KD/BPM model of mania therefore exhibits high levels of face-, construct-, and predictive-validity for the pre-clinical assessment of putative anti-mania drugs. Three different drug regimens - chronic nicotine (nicotinic acetylcholine receptor (nAChR) agonist; 40 mg/kg/d, 26 d), subchronic suramin (anti-purinergic; 20 mg/kg, 1 × /wk, 4 wks), and subchronic resveratrol (striatal DAT upregulator; 20 mg/kg/d, 4 d) - were administered to separate cohorts of male and female DAT KD- and wildtype (WT) littermate mice, and exploration was assessed in the BPM. Throughout, DAT KD mice exhibited robust hyperexploratory profiles relative to WTs. Nicotine partially normalized this behavior. Resveratrol modestly upregulated DAT expression but did not normalize DAT KD behavior. These results support the mania-like profile of DAT KD mice, which may be partially remediated by nAChR agonists via restoration of disrupted catecholaminergic/cholinergic equilibrium. Delineating the precise mechanism of action of nicotine could identify more selective therapeutic targets.

Reduced frequency of Intravitreal methotrexate injection lowers the risk of Keratopathy in Vitreoretinal lymphoma patients.

BACKGROUND: Intravitreal methotrexate has been proven to be an effective treatment method for vitreoretinal lymphoma. However, keratopathy occurs as the major side effect during treatment in most cases. The purpose of this study is to describe the characteristics of primary central nervous system lymphoma (PCNSL) with intraocular involvement and to attempt to reduce the incidence of keratopathy caused by intravitreal methotrexate. METHODS: The medical records of 22 PCNSL patients with intraocular involvement (33 eyes) were reviewed. Patients were divided into two groups. Group A (22 eyes) received the induction-consolidation-maintenance regimen, which consisted of intravitreal methotrexate injection at a dosage of 400 µg/0.1 ml twice a week for the first four weeks, weekly for the following eight weeks, and then monthly for the last nine months. Patients with a poor systemic condition were assigned to Group B (8 eyes), who were started on the treatment protocol described above and switched directly to monthly injection (9 months) when ocular remission was achieved. RESULTS: Blurred vision (31%) and floaters (25%) were common presenting symptoms. Vitritis was the most common clinical sign and was present in 29 eyes (90%) on B-ultrasound examination. Diagnosis was made by 25G-pars plana vitrectomy, and most diagnoses were diffuse large B-cell lymphoma. Ocular remission was achieved after 8.2 (SD = 4.6) injections of methotrexate. The mean VA (visual acuity) was improved from LogMAR 0.65 to 0.3 (P = 0.002). Keratopathy was observed in 21 eyes (66%) after an average of 8.2 (SD = 2.3) injections. With a reduced injection frequency, the incidence of keratopathy was lowered from 86.4% (Group A) to 25.0% (Group B) without ocular recurrence during follow-up. CONCLUSIONS: Intravitreal methotrexate is a safe, effective and flexible treatment for PCNSL patients with intraocular involvement. Keratopathy is the most common adverse effect and can be controlled by reducing the injection frequency.

Vitrectomy for Idiopathic Macular Hole in Patients Aged 80 Years or Older: Efficacy and Safety.

Purpose: To assess the efficacy and safety of idiopathic macular hole (MH) surgery in elderly patients (≥ 80 years of age).Methods: Prospective study enrolled consecutive patients who underwent pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling under retrobulbar anesthesia between February 2016 and May 2018. Twenty-eight eyes of 28 patients aged 80 years or older were classified into the elderly group, a matched group of 56 eyes from 56 younger patients as the control group. The main outcome measures included best-corrected visual acuity (BCVA) and intraoperative and postoperative complications.Results: Statistically, there was no significant difference in visual acuity improvement and incidences of complications between the elderly group and the control group (p = .784 and p = .712, respectively). No operation in either group was postponed or canceled due to complications associated with retrobulbar anesthesia, or physical discomfort before and during the operation. Moreover, no case suffered from myocardial infarction, stroke or death during the perioperative period. Except for one case of retinal detachment postoperatively in the control group, no case required a secondary surgery. All complications were successfully resolved or managed.Conclusions: The results from our study indicate the efficacy and safety of vitrectomy for idiopathic macular hole in patients aged 80 years or older, and idiopathic MH surgery should not be denied on basis of patient age alone.

Exosomes from adipose-derived mesenchymal stem cells ameliorate cardiac damage after myocardial infarction by activating S1P/SK1/S1PR1 signaling and promoting macrophage M2 polarization.

Exosomes derived from mesenchymal stem cells (MSCs) are known to participate in myocardial repair after myocardial infarction (MI), but the mechanism remains unclear. Here, we isolated exosomes from adipose-derived MSCs (ADSCs) and examined their effect on MI-induced cardiac damage. To examine the underlying mechanism, H9c2 cells, cardiac fibroblasts, and HAPI cells were used to study the effect of ADSC-exosomes on hypoxia-induced H9c2 apoptosis, TGF-ß1-induced fibrosis of cardiac fibroblasts, and hypoxia-induced macrophage M1 polarization using qRT-PCR, western blot, ELISA, immunohistochemistry, immunofluorescence and flow cytometry. ADSC-exosome treatment mitigated MI-induced cardiac damage by suppressing cardiac dysfunction, cardiac apoptosis, cardiac fibrosis, and inflammatory responses in vitro and in vivo. In addition, ADSC-exosome treatment promoted macrophage M2 polarization. Further experiments found that S1P/SK1/S1PR1 signaling was involved in the ADSC-exosome-mediated myocardial repair. Silencing of S1PR1 reversed the inhibitory effect of ADSC-exosomes on MI-induced cardiac apoptosis and fibrosis in vitro. ADSC-exosome-induced macrophage M2 polarization was also reversed after downregulation of S1PR1 under hypoxia conditions, which promoted NFκB and TGF-ß1 expression, and suppressed the MI-induced cardiac fibrosis and inflammatory response. In sum, these results indicate that ADSC-derived exosomes ameliorate cardiac damage after MI by activating S1P/SK1/S1PR1 signaling and promoting macrophage M2 polarization.