Dynamic Viral Load Monitoring and Metagenomic Sequencing in Acute Retinal Necrosis Caused by Varicella-Zoster Virus.

PURPOSE: To analyze the trend of intraocular viral load after antiviral treatment in patients with varicella-zoster virus (VZV) induced acute retinal necrosis (ARN), and to explore the effect of viral genotypes on clinical manifestations. METHODS: In this case series, viral load was detected using polymerase chain reaction from aqueous humor during treatment; viral load curves were fitted, and the time required to reach the inflection point between plateau phase and logarithmic reduction phase (Tinflection) was estimated. Variations in viral genomes were detected by metagenomic sequencing. RESULTS: Twenty eyes of 20 patients were included. The median (interquartile range) initial viral load was 5.9×107 (1.1×107-1.1×108) copies/mL. The average duration of retinitis was 5±3 weeks. The average Tinflection was 4.2±1.6 days. Tinflection was correlated with the duration of retinitis (P=0.025). Patients with VZVs carrying the p.S715* variation in ribonucleotide reductase (RNR) subunit 1 gene had lower initial viral loads (median 1.3×107 copies/ml) than those without (median 1.1×108 copies/ml; adjusted P=0.030). CONCLUSIONS: The inflection of viral load curve is helpful to estimate the length of plateau phase and the duration of retinitis during antiviral treatment in ARN patients. Loss-of-function variation in RNR gene might be correlated with lower virulence of VZV.

Elaboration and validation of a novelty nomogram for the prognostication of anxiety susceptibility in individuals suffering from low back pain.

Low back pain (LBP) constitutes a distressing emotional ordeal and serves as a potent catalyst for adverse emotional states, notably anxiety. We dedicated to discerning methodologies for identifying patients who are predisposed to heightened levels of anxiety and pain. A self-assessment questionnaire was administered to patients afflicted with LBP. The pain scores were subjected to analysis in conjunction with anxiety scores, and a clustering procedure was executed using the scientific k-means methodology. Subsequently, six machine learning algorithms, including Logistics Regression (LR), K-Nearest Neighbor (KNN), Decision Tree (DT), Support Vector Machine (SVM), Random Forest (RF), and Extreme Gradient Boosting (XGB), were employed. Next, five pertinent variables were identified, namely Age, Course, Body Mass Index (BMI), Education, and Marital status. Furthermore, a LR model was utilized to construct a nomogram, which was subsequently subjected to assessment for discrimination, calibration, and evaluation of its clinical utility. As a result, 599 questionnaires were valid (effective rate: 99 %). The correlation analysis revealed a significant association between anxiety and pain scores (r = 0.31, P < 0.001). LBP patients could be divided into two clusters, Cluster1 had higher pain scores (P < 0.05) and SAS scores (P < 0.001). The proposed nomogram demonstrated an area under the receiver operating characteristics curve (ROC) of 0.841 (95 %CI: 0.804-0.878) and 0.800 (95 %CI: 0.733-0.867) in the training and test groups, respectively. Briefly, the established nomogram has demonstrated remarkable proficiency in discerning individuals afflicted with LBP who are at a heightened risk of experiencing anxiety.

Prognosis, Risk Factors, and Clinical Features of Intraocular Recurrence in Primary Vitreoretinal Lymphoma.

PURPOSE: To investigate the clinical features, risk factors, and prognosis of the intraocular recurrence in primary vitreoretinal lymphoma (PVRL). DESIGN: Retrospective case-control study. PARTICIPANTS: Ninety-seven eyes of 51 patients diagnosed with PVRL between December 2011 and January 2021 were enrolled in this study. Fourteen patients among them had experienced intraocular recurrence. METHODS: Data on demographic and ophthalmic characteristics, results of diagnostic tests, treatments, and prognosis of intraocular recurrence and nonrecurrence for PVRL patients were collected and compared. Multivariate logistic regression was used to identify independent risk factors. Receiver operating characteristic curves were used to determine the cutoff values. MAIN OUTCOME MEASURES: Clinical features and risk factors. RESULTS: Fourteen (19 eyes) of 51 PVRL patients had intraocular recurrences, resulting in a recurrence rate of 27.5% over a mean follow-up period of 42.5 months. No difference was observed in central nervous system lymphoma (CNSL) relapse rate (54.3% vs. 64.3%, P = 0.52) or median time to CNSL (36.5 months; 95% confidence interval [CI], 24.6-48.3 vs. 37.3 months; 95% CI, 24.8-49.8; P = 0.78) between intraocular nonrecurrence and intraocular recurrence groups. Furthermore, there were no statistically significant differences in the survival outcomes, such as mortality (28.6% vs. 29.7%, P = 1.00) and median overall survival (70.8 months; 95% CI, 54.0-87.7 vs. 59.2 months; 95% CI, 44.8-73.6; P = 0.30), between these 2 groups. Younger onset age (odds ratio [OR] 0.90; 95% CI, 0.84-0.98; P = 0.010), isolated PVRL (OR, 35.3; 95% CI, 2.08-600.0; P = 0.014), and no history of intravitreal chemotherapy (OR, 7.72; 95% CI, 1.37-43.6; P = 0.021) were identified as independent risk factors for intraocular recurrences. Of the patients with intraocular recurrence, 23.6% were asymptomatic and were diagnosed during routine follow-up. The rate of interleukin-10 (IL-10)/interleukin-6 > 1 was significantly lower than that at diagnosis (43.8% vs. 92.3%, P = 0.008). However, the rate of IL-10 ≥ 50 pg/mL was high (81.3%) and not significantly different from that at diagnosis (92.3%, P = 0.61). CONCLUSIONS: This study did not identify an impact of intraocular recurrence on CNS manifestations or survival outcomes in patients with PVRL. Younger patients have a higher risk of intraocular recurrence, and combined systemic and intravitreal chemotherapy may reduce intraocular recurrence. Regular ophthalmic follow-up and IL-10 testing are recommended to detect intraocular recurrence. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Characteristics of Vitreoretinal Lymphoma in B-Scan Ultrasonography: A Case-Control Study.

PURPOSE: To explore the characteristics of vitreoretinal lymphoma (VRL) in B-scan ultrasonography. DESIGN: Single-center case-control study. PARTICIPANTS: A total of 106 eyes of 56 patients with biopsy-proven VRL and 86 eyes of 59 patients with uveitis were included. METHODS: B-scan ultrasonography of the included eyes was performed. Evaluated were the ultrasonographic signs as well as a special pattern termed centrifugal condensation, which refers to the peripherally hyperreflective appearance of the vitreous haze in ultrasonography. MAIN OUTCOME MEASURES: Posterior vitreous detachment, vitreoretinal adhesion, location of vitreous haze, thickening or occupying lesions of the retina, retinal detachment, and centrifugal condensation pattern of vitreous haze were evaluated through B-scan ultrasonography. The incidences of these signs were compared between the 2 groups; odds ratios (ORs) were calculated. RESULTS: The incidence of vitreoretinal adhesion in patients with VRL (6/106) was lower than in patients with uveitis (20/86; P = 0.001; OR: 0.195; 95% confidence interval [CI]: 0.073-0.522). The incidence of retinal thickening or occupying lesions in patients with VRL (21/106) was higher than that in patients with uveitis (1/86; P = 0.005; OR: 19.068; 95% CI: 2.455-148.265). The incidences of posterior vitreous detachment and retinal detachment were not significantly different between the 2 groups (P = 0.453 and P = 0.310, respectively). The centrifugal condensation pattern was more likely to be observed in patients with VRL (49/106) than in patients with uveitis (13/86; P < 0.001; OR: 4.831; 95% CI: 2.416-9.660). CONCLUSIONS: B-scan ultrasonography might help to provide clues for the suspicion of VRL. Thickening or occupying lesions of the retina and centrifugal condensation pattern of vitreous haze might be suggestive of VRL. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Potentiation of the lateral habenula-ventral tegmental area pathway underlines the susceptibility to depression in mice with chronic pain.

Chronic pain often develops severe mood changes such as depression. However, how chronic pain leads to depression remains elusive and the mechanisms determining individuals' responses to depression are largely unexplored. Here we found that depression-like behaviors could only be observed in 67.9% of mice with chronic neuropathic pain, leaving 32.1% of mice with depression resilience. We determined that the spike discharges of the ventral tegmental area (VTA)-projecting lateral habenula (LHb) glutamatergic (Glu) neurons were sequentially increased in sham, resilient and susceptible mice, which consequently inhibited VTA dopaminergic (DA) neurons through a LHbGlu-VTAGABA-VTADA circuit. Furthermore, the LHbGlu-VTADA excitatory inputs were dampened via GABAB receptors in a pre-synaptic manner. Regulation of LHb-VTA pathway largely affected the development of depressive symptoms caused by chronic pain. Our study thus identifies a pivotal role of the LHb-VTA pathway in coupling chronic pain with depression and highlights the activity-dependent contribution of LHbGlu-to-VTADA inhibition in depressive behavioral regulation.

Rab11a in the spinal cord: an essential contributor to complete Freund's adjuvant-induced inflammatory pain in mice.

Inflammatory pain is a commonly observed clinical symptom in a range of acute and chronic diseases. However, the mechanism of inflammatory pain is far from clear yet. Rab11a, a small molecule guanosine triphosphate enzyme, is reported to regulate orofacial inflammatory pain in our previous works. However, the mechanism of Rab11a's involvement in the regulation of inflammatory pain remains obscure. Here, we aim to elucidate the potential mechanisms through which Rab11a contributes to the development of inflammatory pain in the spinal level. It's shown that neurons, rather than glial cells, were the primary cell type expressing Rab11a in the spinal dorsal horn (SDH). After intra-plantar injection of CFA, both the number of Fos/Rab11a-immunopositive neurons and the expression of Rab11a were increased. Administration of Rab11a-shRNA into the SDH resulted in significantly analgesic effect in mice with CFA injection. Application of Rab11a-shRNA also reduced the NMDA receptor-mediated excitatory post-synaptic current (EPSC) and the spike number of neurons in lamina II of the SDH in mice with CFA injection, without affecting the presynaptic glutamate release and the postsynaptic AMPA receptor-mediated EPSC. Our results thus suggest that the enhanced expression of neuronal Rab11a may be important for the process of inflammatory pain in mice with CFA injection, which is likely mediated by Rab11a's potentiation of the competence of post-synaptic NMDAR and spiking of SDH neurons.

Identification and validation of Rab11a in Rat orofacial inflammatory pain model induced by CFA.

Orofacial pain (OFP) is a clinically very common and the most troubling condition; however, there is few effective way to relieve OFP. Rab11a, a small molecule guanosine triphosphate enzyme, is one of the Rab member family playing a vital role in intracellular endocytosis and the pain process. Therefore, we investigated the hub genes of rat OFP model induced by Complete Freund's Adjuvant (CFA) via re-analyzing microarray data (GSE111160). We found that Rab11a acted as a key hub gene in the process of OFP. During the validation of Rab11a, the OFP model was established by peripheral injection of CFA, which decreased the head withdrawal threshold (HWT) and head withdrawal lantency (HWL). Rab11a was observed in NeuN of Sp5C instead of GFAP/IBA-1, and double-IF of Rab11a and Fos positive cells were increased on the 7th day after CFA modeling statistically. Rab11a protein expression in TG and Sp5C of CFA group was also significantly increased. Interestingly, injection of Rab11a-targeted short hairpin RNA (Rab11a-shRNA) into Sp5C could reverse the decrease in HWT and HWL and reduce the expression level of Rab11a. Electrophysiological recording further demonstrated that the activity of Sp5C neuron was improved in CFA group, while Rab11a-shRNA considerably decreased the enhancement of Sp5C neuronal activity. Finally, we detected the expression level of p-PI3K, p-AKT, and p-mTOR in Sp5C of rats after injecting the Rab11a-shRNA virus. To our surprise, CFA upregulated the phosphorylation of PI3K, AKT and mTOR in Sp5C, and Rab11a-shRNA downregulated these molecules' expression. Our data suggest that CFA activates the PI3K/AKT signaling pathway through up-regulating Rab11a expression, which can induce OFP hyperalgesia development furtherly. Targeting Rab11a may be a novel treatment strategy for OFP.

Volume-accumulated reflectivity of the outer retina (integral) on spectral domain optical coherence tomography as a predictor of cone cell density: a pilot study.

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.

Longitudinal Analysis of Ocular Manifestation and Interleukin During Intravitreal Treatment of Vitreoretinal Lymphoma With Methotrexate.

PURPOSE: To explore the trend of ocular manifestations and interleukin (IL) during the treatment of vitreoretinal lymphoma (VRL) and to evaluate the potential effects of different intravitreal administration schedules on the therapeutic response. DESIGN: Interventional comparative nonrandomized clinical study. METHODS: Patients diagnosed with VRL between January 2011 and January 2022 were included. Intravitreal methotrexate (MTX) injections consisting of induction, consolidation, and maintenance were scheduled. At baseline and each visit, ocular manifestations and IL in aqueous humor were recorded. Effects of the variations (eg, frequency and number) in the injection schedule on the therapeutic response were analyzed. RESULTS: Fifty-eight eyes of 33 patients were treated with intravitreal MTX chemotherapy. A mean ± standard deviation of 9 ± 3 injections were given; 52 eyes achieved complete remission (CR). IL-10, keratic precipitates, and subretinal lesions correlated well with the course of treatment (all P < .001). Initial injection given twice weekly was correlated with a higher rate of CR (36/36) than given once weekly or less frequently (16/22; P = .011). Ocular progression occurred in 13 eyes of 8 patients. The completion of schedule was correlated with PFS (induction + consolidation + maintenance: 547 [335-874] days; induction + consolidation: 355 [322-831] days; induction only: 147 [116-187.5] days; P < .001). IL-10 >50 pg/mL was a feasible threshold for the detection of ocular relapse (sensitivity 100.0%, specificity 95.1%). CONCLUSION: Keratic precipitates, subretinal lesions, and IL-10 could serve as indicators for therapeutic response. Intensive initial administration and adequate injection numbers would help to improve the response and prognosis. IL-10 >50 pg/mL could help detect ocular relapse.

Investigating the molecular mechanisms of delirium-like neuropsychiatric disorder induced by electromagnetic pulse based on bioinformatics analysis.

Electromagnetic pulse (EMP), a unique type of electromagnetic radiation, may induce diverse neuropsychiatric disorders, such as irritability, hyperkinesis, retardation of learning and memory. However, the underlying mechanism of EMP exposure on neuronal injury has not been elucidated. Here, we aimed to delineate the regulatory expression networks based on high-throughput sequencing data to explore the possible molecular mechanisms related to EMP-induced delirium-like neuropsychiatric disorder in rats. It's shown that EMP exposure induced anxiety, cognitive decline and short-term memory impairment. The expression profiles of the long noncoding RNAs (lncRNAs) and mRNAs, along with their biological function and regulatory network, were explored in rats after EMP exposure. We identified 41 differentially expressed lncRNAs (DELs) and 266 differentially expressed mRNAs (DEMs) between EMP and sham groups. Sixty-one co-expression relationships between 18 DELs and 56 DEMs were mostly associated with synapse- and metabolic-related pathways. We predicted 51 DEL-miRNA pairs and 290 miRNA-mRNA pairs using the miRanda database to constructed a DEL-miRNA-DEM network. LncRNA AABR07042999.1 and mRNA Tph2, Slc6a4, Dbh and Th were upregulated, and the contents of serotonin, dopamine and norepinephrine were increased in both PFC and HIP after EMP exposure. The current study provided a better understanding of the ceRNA network, which might reveal the pathological mechanism and provide more treatment options for the EMP-induced neurobehavioral disorder.

Retinal changes of primary vitreoretinal lymphoma after intravitreal methotrexate.

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.

Prognostic value of m6A regulators and the nomogram construction in glioma patients.

Although N6-methyladenosine (m6A) has been implicated in various biological functions in human cancers, its role in predicting the prognosis of glioma remains unclear. In this study, the transcriptome expression profiles and the clinical data of 961 patients were derived from the Chinese Glioma Genome Atlas (CGGA). We comprehensively evaluated the association between the expression of m6A regulators and the prognosis of glioma and established a 3-gene (YTHDF2, FTO, and ALKBH5) risk signature using least absolute shrinkage and selection operator (LASSO) analysis. Patients with a high-risk signature had significantly adverse prognoses. Gene set enrichment analysis (GSEA) analysis revealed that the G2M checkpoint, MTORC1 signaling, epithelial mesenchymal transition, and PI3K-AKT-mTOR signaling were significantly enriched in the high-risk group. Univariate and multivariate Cox regression analyses confirmed the independent prognostic value of this risk signature. We then constructed a nomogram for individualized prediction of overall survival (OS) by integrating clinicopathological features (age, World Health Organization [WHO] grade), treatment information (radiotherapy, temozolomide therapy), and m6A risk signature. The calibration curves showed excellent agreement between the predicted and actual probabilities for the 1-, 3-, and 5-year OS, with a C-index of 0.780 in the training cohort and 0.717 in the validation cohort. Altogether, our study elucidated the important role of m6A regulators in glioma prognosis, which is valuable for the selection of therapeutic methods and clinical management of patients with glioma.

Cell-Free DNA Sequencing of Intraocular Fluid as Liquid Biopsy in the Diagnosis of Vitreoretinal Lymphoma.

Purpose: To seek novel diagnostic approaches, we improved the workflow of cell-free DNA (cfDNA) sequencing and evaluated its feasibility in vitreoretinal lymphoma (VRL) specimens; the profile of mutations was preliminarily analyzed for potential diagnostic value. Methods: The study was a diagnostic trial. 23 eyes of 23 patients with VRL and 25 eyes of 25 patients with inflammatory eye diseases were enrolled. Approximate 500µl undiluted vitreous humor and 10ml diluted vitreous fluid was obtained through diagnostic vitrectomy and sent for cytopathological examinations. 500µl of the diluted vitreous fluid was spared for cfDNA sequencing. For cfDNA sequencing, DNA fragmentation procedure was added to the workflow to improve the extraction efficiency; mutations detected were analyzed for potential diagnostic model. The sensitivity and specificity of the cytopathology and cfDNA sequencing were compared. The clinical manifestations were preliminarily analyzed for potential correlations with the genotypes. Results: CfDNA sequencing was accomplished in 23 eyes with VRL and 20 eyes with inflammatory eye diseases. VRL-related mutated genes included MYD88 (18 eyes, 78%), ETV6 (11 eyes, 48%), PIM1 (11 eyes,48%), BTG2 (7 eyes, 30%), IRF4 (7 eyes, 30%), CD79B (6 eyes, 26%), LRP1B (6 eyes, 26%), etc. Logistic regression based on the mutations of MYD88 and ETV6 was of the potential for the diagnosis of VRL (P<0.001, adjusted R2 = 0.789, sensitivity 0.913, specificity 0.950); by comparison, the sensitivity and specificity of the vitreous cytopathology were 0.826 and 1.000, respectively. Further analysis of the mutation profile showed that patients carrying CD79B mutation tended to have higher intraocular interleukin-10 level (P=0.030), that CARD11 mutation was correlated with younger age at ocular onset (P=0.039), and that patients with intracranial involvement carried more multiple-site mutations in the BTG2 gene (P=0.013). Conclusions: The improved workflow of CfDNA sequencing is of sound feasibility in a limited amount of vitreous humor. The logistic model based on the mutations could help to provide reliable clues for the diagnosis of VRL.

PERIVASCULAR FLOWER-BUD-LIKE LESIONS ON EN FACE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN PATIENTS WITH VITREORETINAL LYMPHOMA.

PURPOSE: To describe perivascular flower-bud-like lesions (PFBLs) as novel characteristics of vitreoretinal lymphoma on en face optical coherence tomography (OCT) angiography. METHODS: A retrospective chart review was performed on 23 consecutive patients (35 eyes), who had biopsy-proven vitreoretinal lymphoma between January 2018 and March 2021. En face OCT angiography images were analyzed before and after intervention. PFBLs were initially identified on midretinal slabs of en face OCT angiography, and were further characterized by other imaging modalities. RESULTS: Perivascular flower-bud-like lesions were detected in 12 eyes (34.3%) of 8 patients, of which 8 eyes had best-corrected visual acuity of 20/40 or better. In 10 of the 12 eyes, PFBLs were detected within 6 months of symptom onset. On en face OCT angiography, PFBLs presented as punctate points or confluent bands surrounding retinal vessels, with arterial and venous involvement. In 4 of the 12 eyes, arteries were mainly affected. On OCT B-scans, PFBLs commonly appeared as hyperreflective full-thickness intraretinal lesions that colocalized with subretinal pigment epithelium deposits (3 eyes, 25%) and retinal pigment epithelium irregularities (4 eyes, 33.3%). However, PFBLs could not always be identified on other imaging modalities such as fundus photographs and fundus fluorescein angiography. In all eyes with follow-up, PFBLs attenuated or resolved months after receiving chemotherapy or diagnostic vitrectomy. CONCLUSION: PFBLs are characteristic imaging findings of vitreoretinal lymphoma and may facilitate an early diagnosis of vitreoretinal lymphoma, which would in turn lead to more timely and effective treatment.

Glutamatergic synapses from the insular cortex to the basolateral amygdala encode observational pain.

Empathic pain has attracted the interest of a substantial number of researchers studying the social transfer of pain in the sociological, psychological, and neuroscience fields. However, the neural mechanism of empathic pain remains elusive. Here, we establish a long-term observational pain model in mice and find that glutamatergic projection from the insular cortex (IC) to the basolateral amygdala (BLA) is critical for the formation of observational pain. The selective activation or inhibition of the IC-BLA projection pathway strengthens or weakens the intensity of observational pain, respectively. The synaptic molecules are screened, and the upregulated synaptotagmin-2 and RIM3 are identified as key signals in controlling the increased synaptic glutamate transmission from the IC to the BLA. Together, these results reveal the molecular and synaptic mechanisms of a previously unidentified neural pathway that regulates observational pain in mice.

Blink reflex: A practical test to evaluate the trigeminal nerve injury following percutaneous balloon compression for the treatment of trigeminal neuralgia.

OBJECTIVE: To evaluate the blink reflex (BR) in estimating the potential injury of trigeminal nerve following percutaneous balloon compression (PBC) surgery, and to determine the association between BR alterations and early surgical outcomes. METHODS: In this single-center, prospective before-and-after study, a total of 74 patients who had primary trigeminal neuralgia and scheduled for PBC between October 2020 and June 2021 were prospectively included. BR testing and facial sensory assessment were performed pre- and post-PBC. The latency and the area under the curve (AUC) of pre- and postoperative R1 (R1pre /R1post ) and R2 (R2pre /R2post ) were measured. RESULTS: The BR components were noticeably delayed or diminished following PBC. R1post was elicited in only 26 patients, and absent in 48 patients. The residual R1post had markedly reduced AUC (median difference [Hodges-Lehmann]: -59.5, 95% confidence interval [CI]: -217.5 to -6.9, p = 0.023). Compared with R2pre , the latency of R2post was considerably delayed (mean difference: 4.3, 95% CI: 2.9 to 5.7, p < 0.001) and the AUC was greatly suppressed (median difference [Hodges-Lehmann]: -388.4, 95% CI: -548.4 to -259.5, p < 0.001). After PBC, 58 patients had immediate total pain relief, and 16 had partial relief. The absence of R1post was found in 46 of 58 (79.3%) patients with complete remission, whereas in only 2 of 16 (12.5%) patients with partial relief. Association analysis showed that the absence of R1post was strongly associated with total pain relief (46/58 [79.3%] vs. 2/16 [12.5%], odds ratio [OR]: 26.8, 95% CI: 5.4 to 134.5, Cramér's V: 0.6, p < 0.001). The latency of R2post in patients with total relief was significantly delayed (mean difference: 2.5, 95% CI: 0.3 to 4.6, p = 0.028). Patients experienced graded facial numbness after PBC, of whom 31 reported mild numbness (Grades I-II) and 43 reported more severe numbness (Grades III-IV). The absence of R1post was significantly associated with facial numbness severity, 33/43 (76.7%) in Grades III-IV vs. 15/31 (48.4%) in Grades I-II (OR: 0.284, 95% CI: 0.105 to 0.771, Cramér's V: 0.3, p = 0.012). In patients with more severe numbness, the latency of R2post was significantly delayed (mean difference: 2.7, 95% CI: 0.1 to 5.3, p = 0.043), and the reduction of AUC was much greater (median difference [Hodges-Lehmann]: 17.2, 95% CI: 0.5 to 35.4, p = 0.041). CONCLUSION: Both R1 and R2 were significantly diminished after PBC and these alterations were associated with early surgical outcomes, suggesting that the BR is useful in evaluating trigeminal injury following PBC and could provide objective information about early prognosis.

Facial root entry/exit zone contact in microvascular decompression for hemifacial spasm: a historical control study.

BACKGROUND: Microvascular decompression (MVD) surgery is recognized as an effective treatment for hemifacial spasm (HFS). In MVD surgery, biocompatible materials are usually implanted in situ at the neurovascular conflict site in contact with the offending vessel and the facial root entry/exit zone (REZ). Another procedure of implanting the materials between the responsible vessel and the supraolivary fossa without REZ contact has also been applied. However, it is unclear whether there are any differences between these 2 procedures (REZ-contact procedure vs. REZ-non-contact procedure). Therefore, the aim of the present study was to investigate the effect of the placement of implants (contacting or not contacting the facial REZ) on surgical operations and outcomes. METHODS: A historical control study was performed. Clinical data of HFS patients who underwent MVD between December 2016 and November 2018 were reviewed and categorized into 1 group with the REZ-contact procedure or another group with the REZ-non-contact procedure according to the decompression strategy they received. Clinical demographics, postoperative outcomes, and complications were collected and compared between the two groups. RESULTS: Not all patients are suitable for REZ-non-contact decompression. A total of 205 patients were enrolled: 112 in the REZ-contact group and 93 in the REZ-non-contact group. In the early postoperative period, the complete cure rate in the REZ-non-contact group was significantly higher than that in the REZ-contact group. The reappearance and partial relief rates in the REZ-contact group were significantly higher than those in the REZ-non-contact group. The incidence of short-term neurological complications, especially hearing loss and transient facial palsy, was lower in the REZ-non-contact group (P=0.043). But for long-term follow-up of >1 year, there was no significant difference between the two groups in either curative effects or neurological complications. The operating time for REZ-non-contact decompression was relatively longer than for REZ-contact decompression (P=0.000). An unexpected subdural hemorrhage occurred in the REZ-non-contact group. CONCLUSIONS: REZ-non-contact decompression procedure showed superiority only in short-term postoperative outcomes. Given its limitations and potential risks, the REZ-non-contact procedure can be used as an alternative individualized strategy in MVD, and there is no need to pursue REZ-non-contact during the decompression.

CLINICAL FEATURES, DIAGNOSTIC SIGNIFICANCE, AND PROGNOSIS OF VITREORETINAL LYMPHOMA IN YOUNG PATIENTS.

PURPOSE: To investigate the clinical features, diagnostic approaches, and outcomes of young patients with vitreoretinal lymphoma. METHODS: Fifty-one vitreoretinal lymphoma patients (97 eyes) referred to the Eye and ENT Hospital of the Fudan University from 2011 to 2020 were grouped based on their onset age (age ≤50 years and age >50 years). Complete eye examinations, evaluation of systemic conditions, and biological analysis of intraocular fluids were performed. RESULTS: Young patients accounted for 31.4% (n = 16) of the cohort. More eyes had retinal/subretinal pigment epithelial infiltration (20 [64.5%] vs. 23 [34.8%]; P = 0.018) in young patients than in elderly ones. The mutation rate of Myeloid Differentiation Factor 88 gene (MYD88) was significantly lower in young patients than in elderly ones (5 [50%] vs. 21 [91.3%]; P = 0.016). The median time to new onset of central nervous system lymphoma was significantly shorter in young patients (11.7 vs. 36.2 months; P = 0.012). However, mean overall survival did not differ between the 2 groups (64.9 vs. 57.5 months; P = 0.871). CONCLUSION: Early diagnosis and central nervous system evaluation are crucial for young vitreoretinal lymphoma patients with rapid central nervous system involvement. Meanwhile, young vitreoretinal lymphoma patients have some unique features, including more retinal/subretinal pigment epithelial infiltrations and lower MYD88 mutation rates.

Efficient drug delivery and anticancer effect of micelles based on vitamin E succinate and chitosan derivatives.

Nanocarriers have emerged as a promising cancer drug delivery strategy. Multi-drug resistance caused by overexpression of multiple-drug excretion transporters in tumor cells is the major obstacle to successful chemotherapy. Vitamin E derivatives have many essential functions for drug delivery applications, such as biological components that are hydrophobic, stable, water-soluble enhancing compounds, and anticancer activity. In addition, vitamin E derivatives are also effective mitocan which can overcome multi-drug resistance by binding to P glycoproteins. Here, we developed a carboxymethyl chitosan/vitamin E succinate nano-micellar system (O-CMCTS-VES). The synthesized polymers were characterized by Fourier Transform IR, and 1H NMR spectra. The mean sizes of O-CMCTS-VES and DOX-loaded nanoparticles were around 177 nm and 208 nm. The drug loading contents were 6.1%, 13.0% and 10.6% with the weight ratio of DOX to O-CMCTS-VES corresponding 1:10, 2:10 and 3:10, and the corresponding EEs were 64.3%, 74.5% and 39.7%. Cytotoxicity test, hemolysis test and histocompatibility test showed that it had good biocompatibility in vitro and in vivo. Drug release experiments implied good pH sensitivity and sustained-release effect. The DOX/O-CMCTS-VES nanoparticles can be efficiently taken up by HepG2 cancer cells and the tumor inhibition rate is up to 62.57%. In the in vivo study by using H22 cells implanted Balb/C mice, DOX/O-CMCTS-VES reduced the tumor volume and weight efficiently with a TIR of 35.58%. The newly developed polymeric micelles could successfully be utilized as a nanocarrier system for hydrophobic chemotherapeutic agents for the treatment of solid tumors.