Electroacupuncture Alleviates Cerebral Ischemia-reperfusion Injury by Regulating the S1PR2/TLR4/NLRP3 Signaling Pathway via m6A Methylation of lncRNA H19.

Electroacupuncture (EA) treatment plays a protective role in cerebral ischemiareperfusion (CIR) injury. However, the underlying molecular mechanism is still not fully elucidated. METHODS: All rats were randomly divided into five groups: the SHAM group, MCAO group, MCAO+EA (MEA) group, MCAO+METTL3 overexpression+EA (METTL3) group and MCAO+lncRNA H19 overexpression+EA (lncRNA H19) group. The middle cerebral artery occlusion (MCAO) rats were established to mimic CIR injury. The overexpression of lncRNA H19 and METTL3 was induced by stereotactic injection of lentiviruses into the rat lateral ventricles. The rats in the MEA, METTL3, and lncRNA H19 groups were treated with EA therapy on "Renzhong" (DU26) and "Baihui" (DU20) acupoints (3.85/6.25Hz; 1mA). Besides, the neurological deficit scoring, cerebral infarction area, pathological changes in brain tissue, total RNA m6A level, and the expression of METTL3, S1PR2, TLR4, NLRP3 and lncRNA H19 were detected in this experiment. RESULTS: EA improved the neurological deficit scoring, cerebral infarction area, and pathological injury in MCAO rats, while these beneficial effects of EA on CIR injury were attenuated by the overexpression of METTL3 or lncRNA H19. More importantly, EA down-regulated the total RNA m6A level and the expression of METTL3, S1PR2, TLR4, NLRP3 and lncRNA H19 in MCAO rats. Instead, the overexpression of METTL3 or lncRNA H19 was found to reverse the EA-induced down-regulation. CONCLUSION: The findings indicated that EA might down-regulate the S1PR2/TLR4/NLRP3 signaling pathway via m6A methylation of lncRNA H19 to alleviate CIR injury. Our findings provide a new insight into the molecular mechanism of EA on CIR injury.

Bibliometric Analysis of Non-coding RNAs and Ischemic Stroke: Trends, Frontiers, and Challenges.

More and more articles have shown that non-coding RNAs (ncRNAs) play a significant role in the pathogenesis and prognosis of ischemic stroke. However, the bibliometric analysis in ncRNAs and ischemic stroke is still lacking. This study retrieved the Web of Science Core Collection for relevant articles from January 1, 2010 to April 6, 2023. Bibliometrix R, VOSviewer, and CiteSpace were used to perform the bibliometric analysis. A total of 1058 articles were eligible for this review. The number of publications showed a fluctuating upward trend. The total citations were 28,698 times, and the average number of citations per article was 27.12 times. Our findings indicated ncRNAs has been increasingly investigated for its critical role in apoptosis, autophagy, angiogenesis, inflammation, oxidative stress, and blood-brain barrier after ischemic stroke by regulating target mRNAs, extracellular secretion, target proteins, and others. The microRNAs, circular RNAs, and long ncRNAs may be hotspots, and ferroptosis, METTL3, and exosome might be frontier in this field. Besides, ncRNAs have a promising future as diagnostic and prognostic biomarkers, molecular drug targets, and other targeted therapies for ischemic stroke. However, it still faces many challenges to be successfully applied in the clinical practice.

Prevalence and bidirectional association between rhinitis and urticaria: A systematic review and meta-analysis.

Background: Rhinitis, allergic rhinitis in particular, and urticaria are both common diseases globally. However, there is controversy with regard to the correlation between rhinitis and urticaria. Objective: To examine the accurate association between rhinitis and urticaria. Methods: Three medical literature data bases were searched from data base inception until January 11, 2022. The prevalence and association between rhinitis and urticaria were estimated by meta-analysis. Quality assessment was performed by using the Newcastle-Ottawa Scale. Pooled odds ratios (OR) with 95% confidence intervals (CI) and pooled prevalence were calculated by using random-effects models. Results: Urticaria prevalence in patients with rhinitis was 17.6% (95% CI, 13.2%-21.9%). The pooled prevalence of rhinitis was 31.3% (95% CI, 24.2%-38.4%) in patients with urticaria, and rhinitis prevalence in patients with acute urticaria and chronic urticaria was 31.6% (95% CI, 7.4%-55.8%) and 28.7% (95% CI, 20.4%-36.9%), respectively. Rhinitis occurrence was significantly associated with urticaria (OR 2.67 [95% CI, 2.625-2.715]). Urticaria and rhinitis were diagnosed based on different criteria, possibly resulting in a potential error of misclassification. Conclusion: Rhinitis and urticaria were significantly correlated. Physicians should be cognizant with regard to this relationship and address nasal or skin symptoms in patients.

[Efficacy of electroacupuncture on acute intracerebral hemorrhage and its effect on serum AQP4 in patients].

OBJECTIVE: To observe the effects on neural function, living ability and mental state of the patients with acute intracerebral hemorrhage (ICH), as well as aquaporin 4 (AQP4) in the serum after treated with electroacupuncture (EA) on the base of routine therapy of western medicine. METHODS: Seventy-two acute ICH patients were randomized into an observation group (36 cases, 4 cases dropped off) and a control group (36 cases, 2 cases dropped off). In the control group, the conventional treatment was delivered such as stopping bleeding, preventing re-hemorrhage, controlling blood pressure, mitigating neural edema and reducing intracranial pressure. In the observation group, on the base of the treatment in the control group, EA was supplemented. Acupoints included Shuigou (GV 26), bilateral Neiguan (PC 6) and Sanyinjiao (SP 6) etc. Electric stimulation was operated at Neiguan (PC 6) and Sanyinjiao (SP 6) on the same side, with disperse-dense wave, and 2 Hz/100 Hz in frequency, tolerable current intensity. Electric stimulation was delivered for 30 min in each treatment, once daily and for 6 times per week. The duration of treatment was 2 weeks in the two groups. Before and after treatment, changes of the scores of National Institutes of Health stroke scale (NIHSS), modified Barthel index (MBI) and mini-mental state examination (MMSE), as well as AQP4 content in the serum were observed in the two groups; the efficacy and safety were compared between the two groups. RESULTS: The NIHSS scores and the serum AQP4 content decreased after treatment when compared with those before treatment in the two groups (P<0.05), while, MBI and MMSE scores increased (P<0.05). In the observation group, NIHSS score and serum AQP4 content were lower than those of the control group (P<0.05), and MBI and MMSE scores were higher (P<0.05). The total effective rate of the observation group was 93.8% (30/32), higher than that of the control group (73.5%, 25/34, P<0.05). The treatment in the two groups was safe, without adverse reactions and events occurring in the patients. CONCLUSION: Electroacupuncture, on the base of conventional treatment of western medicine, can effectively improve the neural function, living ability, mental state and serum AQP4 content of the patients with acute ICH. It is suggested that the effective treatment by electroacupuncture may be related to the regulation of the serum AQP4 content.

The prevalence of apathy in stroke patients: A systematic review and meta-analysis.

BACKGROUND: Apathy is a frequent neuropsychiatric disorder in stroke patients. However, its prevalence rates have conflicting results across studies. This meta-analysis aimed to estimate the overall prevalence of apathy in stroke patients from 1990 to 2022. METHODS: PubMed, Web of Science, Embase and PsycINFO were systematically searched to identify relevant articles published from January 1, 1990 to October 29, 2022. Literature quality was assessed with the National Institutes of Health Study Quality Assessment Tool. The pooled prevalence, subgroup analyses and meta-regression were calculated by STATA 16.0. RESULTS: A total of 39 observational studies involving 5168 stroke patients were eligible for this meta-analysis. The pooled prevalence of apathy in stroke patients was 33.0% (95% CI, 27.6-38.4). Subgroup analyses showed that the pooled prevalence of apathy among stroke patients was higher in Japan (36.6%), China (33.7%) and Turkey (63.5%) compared to that in other countries (30.2%). The pooled prevalence of apathy was higher in ischemic stroke samples (36.1%) than in hemorrhagic stroke samples (14.4%). The pooled prevalence of apathy measured with the Apathy Evaluation Scale (38.3%) was the highest in stroke patients. Meta-regression presented that higher literature quality was significantly associated with lower prevalence, while stroke severity, mean age and female percentage were not significantly associated with the prevalence of apathy in stroke patients. CONCLUSION: Our findings revealed that the overall prevalence of apathy in stroke patients was 33.0% based on the current evidence. Furthermore, the prevalence was significantly correlated with countries, stroke subtypes, apathy criteria, and literature quality.

Electroacupuncture Inhibits Ferroptosis Induced by Cerebral Ischemiareperfusion.

BACKGROUND: Electroacupuncture (EA) treatment has been recommended by World Health Organization (WHO) for years on cerebral ischemia treatment, but the specific mechanism is still elusive. Studies have shown that EA can relieve brain damage after ischemic stroke by inhibiting programmed cell death (PCD), such as apoptosis, necroptosis, and autophagy. Ferroptosis, a unique form of cell death, has been highlighted recently and found to occur in I/R injury. We, therefore, investigated whether EA plays an essential role in relieving cerebral I/R injury via ferroptosis. METHODS: The modified MCAO/R rats model was established and then divided into four groups with or without EA treatment. Neurological deficit score and TTC staining were used to evaluate the neurological deficit and infarct volume of each group. Transmission electron microscope (TEM) and immunofluorescence staining were applied for mitochondrial ultrastructure and ROS accumulation observation, respectively. The proteins and mRNA expression of ACSL4, TFR1, and GPX4 were assessed by western blot and qPCR to detect the progress of ferroptosis. RESULTS: EA treatment improved neurological deficits and reduced infarct volume. Moreover, EA significantly relieved the mitochondrial morphological changes and inhibited ROS Production in MCAO rats. In terms of its mechanism, EA obviously decreased the ACSL4 and TFR1 expressions and promoted GPX4 levels in MCAO/R model rats. CONCLUSION: These findings indicate that EA might play an essential role in relieving cerebral I/R injury via ferroptosis.

Electroacupuncture Alleviates Cerebral Ischemia/Reperfusion Injury in Rats by Histone H4 Lysine 16 Acetylation-Mediated Autophagy.

Background: Electroacupuncture (EA) treatment in ischemic stroke has been highlighted recently; however, the specific mechanism is still elusive. Autophagy is considered a new target for cerebral ischemia/reperfusion (I/R), but whether it plays a role of protecting or causing rapid cell apoptosis remains unclear. Studies have reported that the reduction in lysine 16 of histone H4 acetylation coheres with autophagy induction. The primary purpose of the study was to explore whether EA could alleviate I/R via autophagy-mediated histone H4 lysine 16 acetylation in the middle cerebral artery occlusion (MCAO) rat model. Methods: One hundred and twenty male Sprague-Dawley rats were divided into five groups: control group, MCAO group, MCAO+EA group, MCAO+EA+hMOF siRNA group, and MCAO+EA+Sirt1 inhibitor group. EA was applied to "Baihui" (Du20) and "Renzhong" (Du26) at 5 min after modeling and 16 h after the first EA intervention. The structure and molecular markers of the rat brain were evaluated. Results: EA significantly alleviated I/R injury by upregulating the expressions of Sirt1, Beclin1, and LC3-II and downregulating the expressions of hMOF and H4K16ac. In contrast, the Sirt1 inhibitor lowered the increase in Sirt1, Beclin1, and LC3-II and enhanced the level of hMOF and H4K16ac expressions associated with EA treatment. Besides, ChIP assay revealed that the binding of H4K16ac in the Beclin1 promoter region of the autophagy target gene was significantly raised in the MCAO+EA group and MCAO+EA+hMOF siRNA group. Conclusions: EA treatment inhibited the H4K16ac process, facilitated autophagy, and alleviated I/R injury. These findings suggested that regulating histone H4 lysine 16 acetylation-mediated autophagy may be a key mechanism of EA at Du20 and Du26 to treat I/R.