Songdi Wu

Background: Non-arteritic central retinal artery occlusion (NA-CRAO) is an acute ocular emergency that frequently results in severe and irreversible vision loss with limited therapeutic options. Papaverine hydrochloride, a non-specific vasodilator commonly used to relieve vasospasm, has not been previously evaluated for its potential benefits for visual recovery in patients with NA-CRAO. Therefore, this study aims to investigate the association between papaverine hydrochloride treatment (PHt) and functional visual acuity improvement in patients with NA-CRAO. Methods: Propensity-score matching was used to retrospectively collect clinical data of 104 NA-CRAO patients with similar baseline characteristics. The patients were categorized into a PHt group (n = 52) and a non-papaverine hydrochloride treatment (non-PHt) group (n = 52). The primary outcome was functional visual acuity (best-corrected visual acuity ≥20/100) assessed at discharge and at a 1-month follow-up. Logistic regression and subgroup analyses were performed to evaluate the associations between papaverine hydrochloride use and improvements in functional visual acuity. Results: The PHt group showed significantly higher functional visual acuity than the non-PHt group at discharge (32.7% vs. 15.4%, p = 0.039) and at the 1-month follow-up (53.8% vs. 34.6%, p = 0.048). In adjusted models, treatment with papaverine hydrochloride was an independent favorable factor for improved functional visual acuity at discharge (odds ratio [OR] = 3.52, 95% confidence interval [CI]: 1.20–10.36, p = 0.022) and at the 1-month follow-up (OR = 3.15, 95% CI: 1.19–8.29, p = 0.020). Subgroup analyses demonstrated consistent therapeutic effects across age, sex, the side of the affected eye, intra-arterial thrombolysis and intravenous thrombolysis strata, with no statistically significant interaction effects identified at either time point (all Pinteraction >0.05). Conclusion: Treatment with papaverine hydrochloride was significantly associated with visual recovery in patients with NA-CRAO. Prospective further studies of causality are needed to validate these results and assess their safety.

Introduction: Neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD) are among the leading causes of optic neuritis. This study aimed to examine differences in macular retinal structure and microvascular characteristics between affected and unaffected eyes in individuals with NMOSD and MOGAD. Method: This cross-sectional study enrolled both eyes of patients diagnosed with optic neuritis (ON)secondary to NMOSD (22 patients: 36 NMOSD-ON eyes and 8 NMOSD-NON eyes), MOGAD (23 patients: 34 MOG-ON eyes and 12 MOG-NON eyes), and 20 age- and sex-matched healthy controls (HCs, 40 eyes) recruited from the First Affiliated Hospital of Northwest University (Xi’an No.1 Hospital) between February 2023 and January 2025. Microvascular density (MVD), vascular density (VD), blood flow area (BFA), and macular ganglion cell–inner plexiform layer (GCIPL) thickness were measured and analyzed. Result: Both NMOSD-ON and MOG-ON eyes showed significant reductions in MVD of radial peripapillary capillary plexus (RPCP); MVD, VD, and BFA of superficial vascular complex (SVC); BFA of deep vascular complex (DVC); and GCIPL thickness compared with HCs ( P < 0.001). Compared with MOG-ON eyes, NMOSD-ON eyes demonstrated a greater reduction in BFA of choriocapillaris (CC) ( P = 0.040). In MOG-NON eyes, the MVD of RPCP; the MVD, VD, and BFA of SVC; the BFA of DVC; and the GCIPL thickness were significantly lower than those in HCs, but remained higher than in MOG-ON eyes. In NMOSD-ON eyes, all MVD and VD parameters, SVC BFA, and GCIPL thickness were inversely correlated with best-corrected visual acuity (BCVA) and Expanded Disability Status Scale (EDSS) scores ( P < 0.05). In MOG-ON eyes, SVC MVD, VD, and GCIPL thickness were inversely correlated with BCVA and disease duration, while RPCP MVD and SVC BFA were inversely correlated only with BCVA. Conclusion: Both NMOSD and MOGAD cause macular structural and microvascular damage associated with reduced BCVA. Decreased CC BFA may aid in distinguishing NMOSD from MOGAD.

Triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune receptor abundantly expressed in microglia in the brain. Our previous study indicated that TREM2 promoted microglia polarization to the M2 phenotype in APP/PS1 transgenic mice and BV2 cells. It is reported that M2 microglia release brain-derived neurotrophic factor (BDNF) to enhance adult neurogenesis in the hippocampus. However, the role of TREM2 in hippocampal neurogenesis and the underlying mechanism are still less known. Apolipoprotein E knockout (ApoE^−/−) mice exhibit cholinergic dysfunction, tau hyperphosphorylation, synaptic loss and dysfunction that may affect brain function and simulate Alzheimer’s disease (AD). In this study, overexpression of TREM2 significantly increased the number of minichromosome maintenance 2 (MCM2) and doublecortin (DCX) cells in the subgranular zone (SGZ) of ApoE^−/− mice. Additionally, the protein levels of MCM2 and DCX showed a similar trend. Furthermore, we found that overexpression of TREM2 promoted a phenotypical switch from M1 to M2 in microglia, as the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and CD86 were decreased, whereas the levels of IL-4, Arginase-1(Arg-1), BDNF, and CD206 were increased. Importantly, overexpression of TREM2 activated the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) and extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) signaling pathways. In vitro, overexpression of TREM2 in primary microglia increased the production of anti-inflammatory factors (IL-4, Arg-1) and BDNF, while decreasing the production of pro-inflammatory factors (TNF-α, IL-1β). Furthermore, conditioned medium (CM) from TREM2 overexpressing primary microglia facilitated neural stem cells (NSCs) proliferation and differentiation into neurons. Moreover, the mechanistic study indicated that overexpression of TREM2 modulated microglial M2 polarization and promoted the proliferation and differentiation of NSCs partly via the PI3K/Akt and ERK1/2 signaling pathways. Collectively, these findings revealed that TREM2 may modulate microglial M2 polarization to inhibit neuroinflammation and increase the M2 microglia-derived BDNF to rescue hippocampal neurogenesis in ApoE^−/− mice, and TREM2 can be considered a promising therapeutic factor to promote neurogenesis in AD and other brain diseases.

Objectives: To investigate the association between triglyceride-glucose-body mass index (TyG-BMI) and the 1-year stroke recurrence risk in patients with acute ischemic stroke (AIS) and hypertension. Methods: In this retrospective, multicenter cohort study, multivariable Cox proportional hazards models were constructed, and curve fitting and subgroup analyses were performed to evaluate the aforementioned association. TyG-BMI was analyzed as a continuous variable and in quartiles (Q1–Q4). Sex-specific stratified analyses were performed to explore potential effect modifications. Results: Among 1,620 enrolled patients (39.6% women; mean age 65.2 ± 11.5 years), elevated TyG-BMI was significantly associated with increased 1-year stroke recurrence risk after adjusting for potential confounding factors (hazard ratio [HR]=1.06, 95% confidence interval [CI]: 1.01–1.11, P = 0.032). This association was particularly prominent in women (HR = 1.18, 95%CI: 1.07–1.29, P<0.001). Women in the Q3 and Q4 TyG-BMI groups had significantly higher 1-year stroke recurrence risks (Q3: HR=8.81 95%CI: 2.22–34.97, P = 0.002; Q4: HR=5.79 95%CI: 1.49–22.56, P = 0.011) compared with those in the Q1 group. No significant association was observed in men (HR = 1.01, 95%CI: 0.94–1.08, P = 0.830). Segmented linear regression and curve fitting revealed a significant sex-specific nonlinear relationship between TyG-BMI and 1-year stroke recurrence risk. For women when TyG-BMI was below 221.97, each unit increase was associated with a more pronounced increase in the risk of 1-year stroke recurrence compared to patients above this threshold (adjusted HR = 1.04, 95% CI 1.01–1.07, P = 0.005). Conclusion: Elevated TyG-BMI is independently associated with a higher risk of 1-year stroke recurrence in patients with AIS and hypertension. A significant association was identified only in women, specifically among those with a TyG-BMI below 221.97, below which each unit increase in TyG-BMI was associated with a significantly greater risk of 1-year stroke recurrence compared to those above this threshold.

Background: The relationship between abnormal renal function and serum uric acid levels in patients with acute ischemic stroke (AIS) remains insufficiently explored. Although uric acid is associated with cardiovascular and cerebrovascular risk, the specific link between normalized serum uric acid (SUA/SCr) and stroke recurrence in patients with impaired renal function has not been well studied. This study aims to fill this gap by investigating the association between SUA/SCr and 1-year stroke recurrence in patients with AIS and abnormal renal function.Methods: This study utilized the ratio of serum uric acid (SUA) to serum creatinine (SCr) to represent SUA levels normalized for renal function. Abnormal Renal function was defined by the estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m². Multivariable Cox regression, curve fitting, and stratified analyses were employed to assess the relationship between SUA/SCr and 1-year stroke recurrence in patients with AIS and abnormal renal function, considering SUA/SCr as both a continuous variable and in quartiles (Q1–Q4).Results: Of 1,932 enrolled patients (65.3% male; mean age 66.7 ± 11.3 years), each unit of increase in SUA/SCr was associated with a 17% decrease in 1-year stroke recurrence (HR = 0.83, 95% CI 0.73 to 0.96, P = 0.009). Compared to Q1, the Q2 and Q4 groups showed significantly reduced risk in 1-year stroke recurrence (Q2: HR = 0.46, 95% CI 0.27 to 0.79, P = 0.005; Q4: HR = 0.47, 95% CI 0.27 to 0.81, P = 0.007), with a significant trend across all quartiles (P = 0.01 for trend tests). Curve fitting revealed a negative but non-linear correlation. Subgroup analyses showed that in patients with eGFR < 60 ml/min/1.73 m², Q4 had significantly lower 1-year stroke recurrence risk than Q1 (HR = 0.19, 95% CI 0.04 to 0.86, P = 0.031).Conclusion: Low SUA/SCr independently predicts 1-year stroke recurrence in patients with AIS and abnormal renal function, particularly in those with eGFR < 60 mL/min/1.73 m².

Background: Central retinal artery occlusion (CRAO) is a medical condition characterized by sudden blockage of the central retinal artery, which leads to a significant and often irreversible loss of vision. Observational studies have indicated that diabetes mellitus is a risk factor for CRAO; however, there is no research on the causal relationship between diabetes mellitus, particularly type 2 diabetes, and CRAO. This study aimed to perform Mendelian randomization (MR) analysis to clarify the causal relationship between type 2 diabetes and CRAO.Methods: Genetic variants associated with type 2 diabetes were selected from two different datasets. A recent genome-wide association study of CRAO conducted using the FinnGen database was used as the outcome data. A two-sample MR was performed to evaluate the causal relationship between type 2 diabetes and CRAO. Inverse variance weighting was the primary method, and MR-Egger, maximum likelihood, and median weighting were used as complementary methods. A multivariate MR (MVMR) analysis was performed to further evaluate the robustness of the results. Cochran’s Q test, MR-Egger intercept test, and MR-PRESSO global test were used for the sensitivity analyses.Results: Genetically predicted type 2 diabetes was causally associated with CRAO(odds ratio [OR] =2.108, 95% confidence interval [CI]: 1.221–3.638, P=7.423×10^-3), which was consistent with the results from the validation dataset (OR=1.398, 95%CI: 1.015–1.925, P=0.040). The MVMR analysis suggested that type 2 diabetes may be an independent risk factor for CRAO (adjusted OR=1.696; 95%CI=1.150–2.500; P=7.655×10^-3), which was assumed by the validation dataset (adjusted OR=1.356; 95%CI=1.015–1.812; P=0.039).Conclusion: Our results show that genetically predicted type 2 diabetes may be causally associated with CRAO in European populations. This suggests that preventing and controlling type 2 diabetes may reduce the risk of CRAO.

Background and purpose: Considering the reliance of serum uric acid (SUA) levels on renal clearance function, its role in stroke outcomes remains controversial. This study investigated the association of renal function–normalized SUA (SUA to serum creatinine ratio, SUA/SCr), a novel renal function index, with the 1‐year outcomes in patients with acute ischemic stroke (AIS).Methods: This is a prospective, multicenter observational study. Renal function–normalized SUA levels were determined by calculating the ratio of SUA to SCr. One‐year outcomes included stroke recurrence, all‐cause mortality, and poor prognosis. Multivariable Cox regression analyses and restriction cubic splines for curve fitting were used to evaluate SUA/SCr's association with 1‐year stroke outcomes.Results: Among 2294 enrolled patients, after adjustment for potential confounders, multivariable Cox regression analyses showed that each one‐unit increase in SUA/SCr corresponded to a 19% decrease in 1‐year stroke recurrence in patients with AIS. SUA/SCr was analyzed as a continuous variable and categorized into quartiles (Q1–Q4). Compared with the Q1 reference group, Q2, Q3, and Q4 showed significantly lower 1‐year stroke recurrence risks. The trend test indicated significant differences in the 1‐year stroke recurrence trend from Q1 to Q4. In these patients, SUA/SCr did not show a significant association with poor prognosis or all‐cause mortality. Curve fitting revealed SUA/SCr had a negative but nonlinear association with 1‐year stroke recurrence.Conclusions: In patients with AIS, low SUA/SCr may be an independent risk factor for 1‐year stroke recurrence. Changes in SUA/SCr had no significant impact on 1‐year poor prognosis and all‐cause mortality.

Aquaporin-4 antibodies (AQP4-Abs) are a diagnostic marker for patients with a demyelinating disease called neuromyelitis optica spectrum disorder (NMOSD). Anti-Argonaute antibodies (AGO-Abs) present as potential biomarkers of the overlap syndrome between NMOSD and other autoimmune diseases. In this paper, we present the case of an adult woman with numbness, tingling, and burning sensations in her arms and subsequent bilateral internuclear ophthalmoplegia. Brain–cervical–thoracic magnetic resonance imaging (MRI) showed T2 hyperintensities in the dorsal brainstem and around the midbrain aqueduct and longitudinally transverse myelitis with homogeneous enhancement on gadolinium-enhanced MRI. The contemporaneous detection of AQP4- and AGO-Abs led to a definite diagnosis of overlap syndrome of NMOSD with AGO-Abs. The patient was treated with immunosuppressive agents, including corticosteroids and immunoglobulins, and achieved remission. This case highlights a novel phenotype of NMOSD with AGO-Abs overlap syndrome, which presents with relapsing brainstem syndrome and longitudinally extensive myelitis with acute severe neurological involvement. The promising prognosis of the disease could serve as a distinct clinical profile. Broad screening for antibodies against central nervous system autoimmune antigens is recommended in suspected patients with limited or atypical clinical manifestations.