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Neuropathic pain causes enduring physical discomfort and emotional distress. Conventional pharmacological treatments often provide restricted relief and may result in undesirable side effects, posing a substantial clinical challenge. Peripheral and spinal redox homeostasis plays an important role in pain processing and perception. However, the roles of oxidative stress and antioxidants in pain and analgesia on the cortical region during chronic pain remains obscure. Here we focus on the ventrolateral orbital cortex (VLO), a brain region associated with pain severity and involved in pain inhibition. Using a spared nerve injury mouse model, we observed the notable reactive oxygen species (ROS)-mediated suppression of the excitability of pyramidal cells (PYR VLO ) in the VLO. Nasal application or microinjection of the natural antioxidants proanthocyanidins (PACs) to the VLO specifically increased the activity of PYR VLO and induced a significant analgesic effect. Mechanistically, PACs activate PYR VLO by inhibiting distinct potassium channels in different ways: (1) by scavenging ROS to reduce ROS-sensitive voltage-gated potassium currents and (2) by acting as a channel blocker through direct binding to the cap structure of KCNK3 to inhibit the leak potassium current ( I leak ). These results reveal the role of cortical oxidative stress in central hyperalgesia and elucidate the mechanism and potential translational significance of PACs in central analgesia. These findings suggest that the effects of PACs extend beyond their commonly assumed antioxidant or anti-inflammatory effects. Proanthocyanidins enhance pain relief in brain cortex Neuropathic pain is a challenging condition that affects the nervous system, causing abnormal sensations and heightened sensitivity. Researchers explored the potential of proanthocyanidins, natural antioxidants found in plants, to alleviate neuropathic pain. The study involves experiments on mice with nerve injuries to mimic neuropathic pain. Researchers administered proanthocyanidins to the ventrolateral orbitofrontal cortex, a key brain region for pain regulation. They measured pain responses and examined brain activity using various techniques, including electrode recordings and molecular analysis. Results showed that proanthocyanidins decreased pain sensitivity in mice by lowering oxidative stress and modulating specific potassium channels that help control nerve cell activity. This dual mechanism—antioxidant effects and potassium channel regulation—highlights proanthocyanidins as an alternative to conventional pain treatments. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.

Background To identify retinal changes using spectral-domain optical coherence tomography (SD-OCT) and ultra-widefield images in eyes with primary vitreoretinal lymphoma (PVRL) during intravitreal methotrexate (MTX) treatment.  Methods This study retrospectively reviewed 111 eyes of 58 patients with vitreous cytology-proven confirmed PVRL, who received intravitreal injections of MTX. Results At the initial visit, the OCT manifestations included vitreous cells (105 eyes, 94.6%), intraretinal infiltration (44 eyes,39.6%), subretinal infiltration (45 eyes, 40.5%,), retinal pigment epithelium (RPE) abnormalities (66 eyes, 59.5%), disruption of the ellipsoid zone (58 eyes, 52.3%), subretinal fluid (4 eyes, 3.6%), RPE detachment (PED) (28 eyes, 25.2%), epiretinal membrane (ERM) (8 eyes, 7.2%), macular edema (10 eyes, 9%). After therapy, tumor regression was achieved in all eyes. Between the initial presentation and regression, the vitreous cells (94.6% vs. 0%, P  < 0.001), intraretinal infiltration (39.6% vs. 0%, P  < 0.001), RPE abnormalities (59.5% vs.19.8%, P  < 0.001), PED (25.2% vs.0%, P  < 0.001), and subretinal infiltration (40.5%vs.16.2%, P  < 0.001) were significantly reduced. The fundus photography findings all improved after therapy. The mean Logarithm of the Minimum Angle of Resolution (logMAR) for the best corrected visual acuity (BCVA) at presentation was 0.79 ± 0.81 (range, 0–2.9), which improved to 0.70 ± 0.97 (range, 0–2.9, P  = 0.01) at the final visit. Conclusions SD-OCT combined with ultra-widefield imaging, which can reflect retinal changes, are valuable tools for monitoring the effect of PVRL treatment.

Programmed death ligand 1 (PD-L1) is a potential target for autoimmune disease therapies. The gut microbiota plays a critical role in autoimmunity, and may influence therapeutic outcomes of immune therapies in cancer. However, the relationship between PD-L1 and gut microbiota in autoimmune conditions remains unclear. This study aims to investigate the effect of PD-L1 knockout on gut microbiota in an experimental autoimmune uveitis (EAU) model. EAU was induced via immunization with interphotoreceptor retinoid-binding protein peptide 651-670 (IRBP651-670) in either wild type (WT) or PD-L1 knockout (KO) C57BL/6J female mice. Sham adjuvant was administered to WT or PD-L1 KO mice as healthy controls. The severity of EAU was evaluated through clinical evaluation and histopathological gradings. The characteristics of gut microbiota was analyzed using metagenomic sequencing. Each group consisted of three biological replicates. The clinical and histopathological scores of EAU were significantly higher in KO_EAU mice than in WT_EAU mice. WT_EAU mice exhibited lower microbial richness than their healthy controls (WT mice), while PD-L1 KO in EAU mice (KO_EAU group) led to increased richness when compared to wild type EAU mice (WT_EAU group). EAU induced a reduction in the abundance of and an increased in sp . PD-L1 knockout in EAU led to an increased abundance of families Bacteroidaceae, Lachnospiraceae and Ruminococcaceae. EAU was associated with declining microbial tryptophan metabolism and up-regulated functions related to lipid and carbohydrate metabolism; PD-L1 knockout in EAU further increased the metabolism of glycan and biosynthesis of 3-deoxy-α-D-manno-2-octulosonate (Kdo), a key component of bacterial lipopolysaccharide (LPS). Both EAU and PD-L1 knockout modulate gut microbiota, affecting microbial composition - particularly , , Bacteroidaceae, Lachnospiraceae and Ruminococcaceae - and microbial functions such as lipid, carbohydrate and glycan metabolism.

Inflammatory pain is one of the most common symptoms of clinical pain that seriously affects patient quality of life, but it currently has limited therapeutic options. Proanthocyanidins, a group of polyphenols enriched in plants and foods, have been reported to exert anti-inflammatory pain alleviating effects. However, the mechanism by which proanthocyanidins relieve inflammatory pain in the central nervous system is unclear. In the present study, we observed that intrathecal injection of proanthocyanidins inhibited mechanical and thermal pain sensitivity in mice with inflammatory pain induced by complete Freund’s adjuvant (CFA) injection. Electrophysiological results further showed that proanthocyanidins inhibited the frequency of spontaneous excitatory postsynaptic currents without affecting the spontaneous inhibitory postsynaptic currents or the intrinsic properties of parabrachial nucleus-projecting neurons in the spinal cord. The effect of proanthocyanidins may be mediated by their inhibition of phosphorylated activation of the PI3K/Akt/mTOR pathway molecules in dorsal root ganglia neurons. In summary, intrathecal injection of procyanidin induces an obvious anti-inflammatory pain alleviating effect in mice by inhibiting peripheral excitatory inputs to spinal neurons that send nociceptive information to supraspinal areas.

PurposeThere exist different opinions on whether the anatomical laterality of vertebral artery (VA) is related to the unilateral onset of hemifacial spasm (HFS). In this study, we intended to qualitatively explore the potential correlation between the anatomical deviations of VA and the clinical characteristics of HFS.MethodsTwo hundred and forty patients who underwent microvascular decompression for HFS between January 2018 and December 2019 were recruited. Clinical data including medical records and preoperative MRI images were retrospectively reviewed. A score system was specially designed for VAs to illustrate their distribution, and a score-weighted cross-sectional area of VA was proposed to represent the relative thickness of VA on each side. Then, the anatomical deviations of VA were comparatively analyzed between the symptomatic side and asymptomatic side and between VA-involved cases and non-VA-involved cases.ResultsThe score and weighted cross-sectional area (WCSA) of VA in symptomatic side were significantly greater than those in asymptomatic side (P = 0.000, P = 0.000). And in symptomatic side, the score and WCSA of VA in VA-involved cases were significantly greater than those in non-VA-involved cases (P = 0.000). Moreover, with higher score (P = 0.000) and greater WCSA (P = 0.001) on the left side, the VA-involved cases showed a preference (74%) of left HFS.ConclusionsIn HFS, the symptomatic side tends to have an ipsilaterally deviated and relatively larger VA, especially in VA-involved cases. And it is the VA-involved cases that are prone to have a prevalence of left HFS, but not the non-VA-involved cases.

Background The study aims to investigate the relationship between the volume-accumulated reflectivity (termed “integral”) on spectral domain optical coherence tomography (SD-OCT) and cone density on adaptive optics (AO) imaging. Methods In this cross-sectional study, both eyes of 32 healthy subjects and 5 patients with inherited retinal diseases (IRD) were studied. The parameter, integral, was defined as the volume-accumulated reflectivity values in a selected region on OCT images; integrals of the ellipsoid zone (EZ) and interdigitation zone (IZ) were measured at 2°, 3°, 4°, 5°and 6° eccentricity along the four meridians on fovea-centered OCT B-scans. Cone density in the same region was measured using a flood illumination adaptive optics camera RTX1. Results Integrals of EZ, IZ and cone density shared similar distribution patterns. Integral of the IZ was better correlated with cone density in both healthy people (r = 0.968, p  < 0.001) and those with IRD (r = 0.823, p  < 0.001) than direct measurements of reflectivity on OCT images. A strong correlation was found between best corrected visual acuity (BCVA) and cone density at 2° eccentricity (r = -0.857, p  = 0.002). BCVA was also correlated with the integral of the IZ at the foveola (r = -0.746, p  = 0.013) and fovea (r = -0.822, p  = 0.004). Conclusions The new parameter “integral” of the photoreceptor outer segment measured from SD-OCT was noted to correlate with cone density and visual function in this pilot study.

Background To investigate the effect of intravitreal conbercept (IVC) injections on the incidence of postoperative vitreous hemorrhage (VH) in eyes undergoing surgery for severe proliferative diabetic retinopathy. Methods This was a pilot prospective, comparative, and randomized study. Thirty patients, who underwent vitrectomy for severe proliferative diabetic retinopathy, were assigned randomly to either group 1 (intravitreal conbercept [IVC] injection at the end of pars plana vitrectomy) or group 2 (no IVC injection). Postoperative follow-up was performed on the first day, first week, first month, third month, sixth month and first year after surgery. The primary outcome was the incidence of postoperative VH. Secondary outcomes were the initial time of vitreous clearing (ITVC), best-corrected visual acuity (BCVA) and central retinal thickness (CRT) after surgery. Results A total of 30 eyes, from 30 patients, were included. Fifteen eyes were enrolled in the IVC group and fifteen in the control group. The incidence of early and late postoperative VH was not significantly different between the control and IVC groups. ITVC was shorter in the IVC group than that in the control group, but this was not significant (7.38 ± 10.66 vs 13.23 ± 17.35, P  = 0.31). Final BCVA, 1 year after surgery, showed significant improvement compared to baseline in both groups. However, analysis of the BCVA at any postoperative visit after surgery showed no significant differences between the two groups. There were two cases of recurrent VH identified at 3 and 6 months after surgery in each group, requiring a second round of surgery. Foveal thickness was significantly different between the two groups at the 3-month, 6-month and 1-year follow-up visits. Conclusions In this pilot study, the effect of IVC injection in reducing the incidence of postoperative VH after diabetic vitrectomy at the end of vitrectomy was not shown. Trial registration The study was registered with the Chinese Clinical Trial Registry. (Reference Number: ChiCTR1800015751 ).

Background Interleukin detection is helpful in screening vitreoretinal lymphoma (VRL). However, the levels of interleukin in aqueous humor (AqH) can be abnormally low in some cases, leading to underdiagnosis of VRL merely dependent on AqH. The purpose of this study was to investigate the correlation of interleukins between paired AqH and vitreous humor (VH) samples in VRL cases, and to explore potential factors affecting interleukin levels and diagnostic parameters. Methods This was a case series study. Reviewed were consecutive biopsy-proven B-cell VRL cases of which adequate paired AqH and VH samples were obtained for the measurement of interleukin 10 (IL-10) and interleukin 6 (IL-6). The correlations of IL-10 and IL-6 between AqH and VH were analyzed. Influences of clinical manifestations on IL levels and positive rates of IL-related parameters in AqH and VH were evaluated, which included AqH IL-10 > 30 pg/mL, VH IL-10 > 65 pg/mL, IL-10/IL-6 ratio > 1, and Interleukin Score for Intraocular Lymphoma Diagnosis (ISOLD) > 0 in both the AqH and VH. Results Seventy-four eyes of 64 patients with VRL were included. IL-10 in VH was significantly higher than in AqH (median: 1159.77 vs. 225.74 pg/mL, P  < 0.001). For both IL-10 and IL-6, the AqH concentrations were positively correlated with VH concentrations in the form of power functions ( P  < 0.001 and P  < 0.001, respectively). The positive rate of AqH IL-10/IL-6 > 1 (77%) was lower than that of VH IL-10 > 65 pg/mL (91%), VH IL-10/IL-6 > 1 (89%) and VH ISOLD > 0 (91%). Eyes without intraretinal infiltration tended to have lower IL-10 levels in the AqH and VH (median: 141.08 pg/mL vs. 449.10 pg/mL, 825.48 pg/mL vs. 2285.77 pg/mL; P  = 0.001 and P  < 0.001, respectively), and lower positive rates of AqH IL-10 > 30 pg/mL (78% vs. 97%, P  = 0.018) and AqH ISOLD > 0 (76% vs. 97%, P  = 0.033). Conclusions IL-10/IL-6 in AqH may not be as sensitive as the parameters (including IL-10, IL-10/IL-6 and ISOLD) in VH for VRL screening. Cases without intraretinal involvement were less likely to be positive for IL-10 > 30 pg/mL and ISOLD > 0 in AqH; the possibility of VRL should be ruled out more cautiously in these cases.

Neuropathic pain (NP) represents a considerable clinical challenge, profoundly impacting patients’ quality of life. Presently, pharmacotherapy serves as a primary approach for NP alleviation, yet its efficacy often remains suboptimal. Melatonin (MLT), a biologically active compound secreted by the pineal gland, has long been associated with promoting and maintaining sleep. Although recent studies suggest analgesic effects of MLT, the underlying mechanism remains largely unknown, particularly its impact on the cortex. In this study, we induced an NP model in mice through spared nerve injury (SNI) and observed a considerable, dose-dependent alleviation in NP symptoms following intraperitoneal or anterior cingulate cortex (ACC) administration of MLT. Our findings further indicated that the NP management of MLT is selectively mediated by MLT-related receptor 2 (MT 2 R), rather than MT 1 R, on neurons and microglia within the ACC. Transcriptome sequencing, complemented by bioinformatics analysis, implicated MLT in the modulation of Gα(i) and immune-inflammatory signals. Specifically, MLT inhibited the excitability level of pyramidal cells in the ACC by activating the Gα(i) signaling pathway. Simultaneously, MLT attenuated M 1 polarization and promoted M 2 polarization of microglia, thereby mitigating the inflammatory response and type II interferon response within the ACC. These findings unveil a hitherto unrecognized molecular mechanism: an MLT-mediated neuroimmune modulation pathway in the ACC mediated by MT 2 R. This elucidation sheds light on the regulatory character of MLT in chronic nociceptive pain conditions, offering a prospective therapeutic strategy for NP management.

PurposeTo investigate ultrasound biomicroscopy (UBM) characteristics of patients with ocular toxocariasis (OT) and to explore the role of UBM in the diagnosis and differential diagnosis of OT.DesignCross-sectional study.Methods78 eyes of 77 patients clinically consistent with OT and confirmed by serum and/or intraocular antibodies in a single tertiary centre (Fudan University Eye and ENT Hospital, Shanghai) between July 2009 and July 2016 were included in the study. UBM was performed, and the outcomes were analysed.ResultsMean age of the patients included was 12.8±10.3 years. Positive UBM findings were observed in 72 of 78 eyes (92.3%). The primary imaging feature was peripheral granulomas (66 eyes; 84.6%), of which 78.5% were adjacent to the nasal or temporal side of horizontal meridian and 79.7% located on the surface of the ciliary body, presenting as olivary foci on radical section and botuliform foci on coronal section. Moreover, 12 of the peripherally involved eyes were accompanied with posterior pole granulomas, which could be termed ‘combined type’. Other UBM findings included vitreous strands (53 eyes; 67.9%), peripheral tractional retinal detachment (41 eyes; 52.6%) and tractional cyclodialysis (32 eyes; 41.0%).ConclusionsThe utilisation of UBM verifies the existence of the combined subtype (with both peripheral and posterior pole granulomas) and improves the detection rate of peripheral granulomas, which is of great importance to the diagnosis and differential diagnosis of OT.