Xiaoming Rong

Background: For patients with large‐vessel occlusion stroke who undergo endovascular thrombectomy without prior intravenous thrombolysis, the efficacy and safety of adjunctive intra‐arterial alteplase (IAA) after successful endovascular reperfusion remain uncertain. Methods: This was a prespecified subgroup analysis of the PEARL (Intra‐Arterial Alteplase After Successful Endovascular Reperfusion in Acute Stroke) randomized clinical trial conducted at 28 centers in China, focusing on patients who underwent endovascular thrombectomy without prior intravenous thrombolysis. Patients were stratified by treatment assignment: IAA treatment versus standard treatment (control). The primary efficacy outcome was the proportion of patients achieving excellent functional outcome, defined as a modified Rankin Scale score of 0 to 1 at 90 days. Safety outcomes included symptomatic intracranial hemorrhage, any intracranial hemorrhage within 36 hours, and 90‐day all‐cause mortality. Results: Among 324 patients originally randomized in the PEARL trial, 189 underwent endovascular thrombectomy without prior intravenous thrombolysis and were included in this analysis. Of the 189 patients, 95 were assigned to the IAA treatment group and 94 to the standard treatment group. Excellent functional outcome at 90 days was significantly higher in the IAA treatment group compared with the standard treatment group (43.2% [41/95] versus 22.6% [21/93]; adjusted risk ratio [aRR], 1.86; 95% CI, 1.19–2.91; P= 0.007). The absolute risk reduction was 20.6% (95% CI, 7.0%–33.1%). Results were consistent in per‐protocol sensitivity analyses ( P= 0.002). No significant differences were observed in symptomatic intracranial hemorrhage (aRR, 0.93; 95% CI, 0.28–3.13; P= 0.908), any intracranial hemorrhage (aRR, 1.04; 95% CI, 0.68–1.60; P= 0.843), or 90‐day mortality (hazard ratio [HR], 1.00; 95% CI, 0.49–2.04; P >0.99). Conclusions: In patients who did not receive prior intravenous thrombolysis, adjunctive IAA after successful endovascular thrombectomy was associated with a higher likelihood of excellent functional outcome at 90 days, without an apparent increase in symptomatic intracranial hemorrhage or mortality. Registration: URL: clinicaltrials.gov ; Unique Identifier: NCT05856851.

Purpose: Cognitive decline is a major concern for nasopharyngeal carcinoma (NPC) survivors after radiotherapy (RT). We assessed whether the rates of cognitive decline in NPC survivors differed depending on the presence of epilepsy. Methods: Based on an ongoing prospective cohort study (NCT03908502), we included consecutive NPC patients with a history of radiotherapy who underwent a baseline and follow-up cognition assessment between January 2005 and December 2023. Patients who had a confirmed diagnosis of epilepsy before radiotherapy, had intracranial brain metastasis during follow-up, lacked baseline major clinical data, or lacked follow-up cognitive assessment of longer than six months were excluded. The outcome was cognitive function assessed by the Chinese version of the Montreal Cognitive Assessment (MoCA), with assessments being performed every 6 months through face-to-face interviews. Linear mixed-effect models were used to analyze the progression rate of MoCA scores by epilepsy status (incident, prevalent, or no epilepsy). Results: A total of 521 patients with a median follow-up period of 3.96 years were included in our study. The rate of decline in MoCA was significantly faster in patients with prevalent epilepsy compared with no epilepsy after adjusting for demographics, health behaviors, tumor-related history, complications, anti-seizure medication, and inflammatory blood index (estimate: −1.407; 95%CI: −2.419, −0.412; p = 0.007). However, the cognitive decline rate was similar in the incident epilepsy group compared with that in the non-epilepsy group (p = 0.126). Subgroup analysis showed that there was no significant difference in the effect of epilepsy status on cognitive deterioration among subgroups stratified by the pre-planned covariates. Conclusions: Global cognitive function declined more rapidly in NPC patients with prevalent epilepsy. The control of seizure attacks may be valuable to mitigate cognitive decline.

Malnutrition is related to worsened prognosis, but the association between nutritional risk status and overall survival in radiation-induced brain necrosis (RN) has never been studied. We included consecutive patients who had received radiotherapy for head and neck cancer (HNC) and subsequently developed RN from 8 January 2005 through to 19 January 2020. The primary outcome was overall survival. We utilized three commonly-used nutritional assessments: the Geriatric Nutritional Risk Index (GNRI), Prognostic Nutritional Index (PNI), and the COntrolling NUTritional Status (CONUT) measure, to quantify the baseline nutritional risk. A total of 398 eligible patients were included. During a median follow-up of 2.3 years, 42 (10.6%) patients died of any cause. Malnutrition at admission was associated with an increased risk of future death, as assessed by the GNRI (per 1-point decreased, HR 1.05, 95%CI 1.02–1.09, p = 0.001), the PNI (per 1-point decreased, HR 1.07, 95%CI 1.03–1.12, p = 0.002), and the CONUT (per 1-point increased, HR 1.22, 95%CI 1.08–1.37, p = 0.001). There were no nonlinear correlations between all three indices and post-RN survival. Among HNC survivors with RN, the assessment of nutritional risk by composite indices upon admission could help identify patients who might be at high risk of future death and deliver better nutritional management.

B a ckground: Circular RNAs (circRNAs) have been crucially implicated in various diseases, however, their involvement in chronic intermittent ethanol (CIE) exposure remains unclear. O bjective: The present study was conducted to evaluate the circular RNA expression alteration in brain samples and to identify the molecular mechanisms underlying chronic intermittent ethanol exposure. M ethods: Male C57BL/6J mice (10 for each group) were given 4 weeks of chronic intermittent ethanol exposure. Whole brain samples were collected for high-throughput sequencing and circRNA bioinformatic analysis. Real-time quantitative PCR (RI-qPCR) and agarose electrophoresis were used to validate the differentially expressed circRNAs. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) analysis were performed. A p level < 0.05 was considered statistically significant. R esults: Compared with the control group and baseline values, the CIE group showed a significant increase in ethanol intake. High-throughput sequencing revealed 399 significantly different circRNAs in CIE mice, including 150 up-regulated circRNAs and 249 down-regulated circRNAs. GO analysis showed that the most significantly enriched term for biological process, cellular component, and molecular function were GO:0050885, GO:0016020 and GO:0005515, respectively. The most enriched pathways in KEGG analysis were GABAergic synapse (mmu04727), followed by retrograde endocannabinoid (eCB) signaling (mmu04723) and morphine addiction (mmu05032). Among the circRNAs, RT-qPCR confirmed 14 upregulated and 13 downregulated circRNAs in the brain tissues with 9 upregulated and 10 downregulated circRNAs being observed in blood samples. C onclusions: Our study suggests that chronic ethanol exposure upregulates or downregulates circRNAs in the brain, which, in turn, could alter neurotransmitter release and signal transduction.

Background and purpose: Glioma is a frequent primary brain tumor. MicroRNAs (miRNA) have been shown to potentially play a crucial part in tumor development. Based on miRNAs and clinical factors, a model was constructed to predict the glioma prognosis. Methods: The miRNA expression profiles of glioma come from The Cancer Genome Atlas (TCGA, training group) and Chinese Glioma Genome Atlas (CGGA, validation group). Regression analyses of Cox and Lasso were applied to identity miRNAs associated with glioma prognosis in the TCGA database. The miRNAs were combined with clinical factors to construct individualized prognostic prediction models, whose performance was validated in the CGGA database. The role of miRNA in glioma development was investigated by in vitro experiments. Results: We identified five key miRNAs associated with glioma prognosis and constructed a prediction model. The area under ROC curve for predicting 3-year survival of glioma patients in the TCGA and CGGA groups was 0.844 and 0.770, respectively. The nomogram constructed using the miRNA risk scores and clinical factors showed high accuracy of prediction in the TCGA group (C-index of 0.820) and the CGGA group (C-index of 0.722). The miR-196b-5p altered the migration, proliferation, invasion, and apoptosis of glioma cells by regulating target genes, according to in vitro experiments. Conclusions: A miRNA-based individualized prognostic prediction model was constructed for glioma and miR-196b-5p was identified as a potential biomarker of glioma development.

Background: The controlling nutritional status (CONUT) score and the prognostic nutritional index (PNI) score were designed as indicators of patients’ immune-nutritional status. This study aimed to investigate the prognostic impact of the CONUT and PNI scores on long-term recurrent ischemic stroke (RIS) and adverse outcomes for adults with acute ischemic stroke (AIS). Methods: This retrospective study enrolled 991 AIS patients. Multivariable Cox regression models were used to assess the relationships of the malnutritional indices and RIS and major cardiovascular events (MACEs). Results: During a median follow-up at 44 months (IQR 39–49 months), 203 (19.2%) patients had RIS and 261 (26.3%) had MACEs. Compared with normal nutritional status, moderate to severe malnutrition was significantly related to an increased risk of RIS in the CONUT score (adjusted hazard ratio (HR) 3.472, 95% confidence interval (CI) 2.223–5.432, p < 0.001). A higher PNI value tertile (tertile two, adjusted HR 0.295, 95% CI 0.202–0.430; tertile three, adjusted HR 0.445, 95% CI 0.308–0.632, all p < 0.001) was related to a lower risk of RIS. Similar results were found for MACEs. The PNI exhibited nonlinear association with the RIS and both two malnutritional indices improved the model’s discrimination when added to the model with other clinical risk factors. Conclusions: This study demonstrated that the CONUT and PNI are promising, straightforward screening indicators to identify AIS patients with impaired immune-nutritional status at higher risk of long-term RIS and MACEs.

Background and purpose: The optimal treatment for acute ischemic stroke with mild neurologic deficits is unclear. We aimed to compare the efficacy and safety of alteplase versus dual-antiplatelet therapy in acute minor stroke. Methods: We performed a retrospective cohort study of patients with minor ischemic stroke and National Institutes of Health Stroke Scale scores ≤5 presenting within 24 h from last seen normal. Patients were divided into intravenous alteplase or dual-antiplatelet therapy group. The primary outcome was a modified Rankin Scale (mRS) score of 0 or 1 at 90 days. Secondary outcomes included mRS score at 7 days, and composite outcome of vascular events within 90 days. The safety outcome was any intracranial hemorrhage (ICH) according to the ECASS II criteria. Clinical outcomes were compared using a multivariable logistic regression after adjusting for confounding factors. We then performed the propensity score matching as a sensitivity analysis. Results: Two hundred twenty-eight patients met the eligibility criteria were included for analysis between January 2015 and September 2018. In the aspirin-clopidogrel group, 109 patients (91.6%) achieved a favorable functional outcome at 3-month versus 85(78.0%) in the alteplase group (OR 4.463, 95%CI 1.708–11.662, p = .002). The difference of the composite outcome of vascular events were not statistical significance between the two groups (p > .05). Asymptomatic ICH occurred in 0.8% patients who received aspirin-clopidogrel, as compared with 3.7% patients in alteplase group (p = .030). Conclusions: Patients treated with dual-antiplatelet therapy with acute minor ischemic stroke had greater functional outcome at 3 months compared with patients who received alteplase therapy. Classification of evidence: This study provides Class IV evidence that dual-antiplatelet therapy is superior to alteplase for achieving a better functional outcome and does not increase the risk of hemorrhage in acute minor ischemic stroke.

Background: Multiple sclerosis (MS) is an autoimmune and demyelinating disease. Genome-wide association studies have shown that MS is associated with many genetic variants in some human leucocyte antigen genes and other immune-related genes, however, those studies were mostly specific to Caucasian populations. We attempt to address whether the same associations are also true for Asian populations by conducting whole-exome sequencing on MS patients from southern China. Methods: Genomic DNA was extracted from the peripheral blood mononucleocytes of 8 MS patients and 26 healthy controls and followed by exome sequencing. Results: In total, 41,227 variants were found to have moderate to high impact on their protein products. After filtering per allele frequencies according to known database, 17 variants with the allele frequency T, Ala322Ser, rs201693690) was found to be a novel missense variant. Conclusion: MS in southern China may have association with unique genetic variants, our data suggest TRIOBP as a potential novel risk gene.