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.

Synergistic Effect of Ion Doping and Type-II Heterojunction Construction and Ciprofloxacin Degradation by MIL-68(In,Bi)-NH2@BiOBr under Visible Light.

Heterojunction structure and ion doping techniques are viable tactics in facilitating the generation and separation of photogenerated electrons and holes in photocatalysis. In the current study, a novel Bi ion-doped MIL-68(In,Bi)-NH2@BiOBr (MIBN@BOB) type-II heterojunction was first synthesized in a one-step solvothermal reaction. Doping of Bi ions not only broadened the light-sensing range but also provided reliable anchor sites for the in situ growth of BiOBr. Meanwhile, the heterostructure supplied new channels for photogenerated carriers, accelerating the transfer and inhibiting the recombination of photogenerated electron-hole. The obtained MIBN@BOB exhibited enhanced photocatalytic performance (91.1%) than MIL-68(In)-NH2 (40.8%) and BiOBr (57.5%) in ciprofloxacin (CIP) degradation under visible light, with excellent reusability. Photocatalysts were characterized in detail, and a series of photoelectrochemical tests were utilized to analyze the photoelectric properties. MIBN@BOB were deduced to conform the electron conduction mechanism of conventional type-II heterojunctions. More importantly, based on the above experiments and density functional theory (DFT) calculation, BiOBr-Bi in MIBN@BOB can serve as the major active sites of CIP enrichment, and •O2- and 1O2 generated at the BiOBr interface can react with the adsorbed CIP directly. Lastly, the possible degradation products and pathways of CIP were analyzed by liquid chromatography-tandem mass spectrometry (LC/MS/MS). This study provides a reference for the construction of ion-doping-modified metal-organic framework (MOF)-based heterojunction photocatalysts and their application in antibiotic removal.

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.

Role of Ferroptosis in Glial Cells after Ischemic Stroke.

Ischemic stroke (IS) is the predominant cause of morbidity and mortality worldwide. Ferroptosis, a new type of programmed cell death, has been shown to play a crucial role in IS pathogenesis. Traditionally, research focused on neurons did not uncover specific positive results for IS. However, glial cells have recently received interest as promising targets for IS treatment, not only for their structural function but also in the iron transfer between glia and neurons, which indicates a promising glia-neuron crosstalk in mediating the IS process and ischemia/reperfusion-associated neuropathology, showing their affiliation with ferroptosis. This review addresses the major phenomena of iron metabolism and the process and regulation of ferroptosis, with a particular focus on their impact on IS pathology. The review discusses iron homeostasis, the biology of reactive oxygen species, and lipid peroxidation for modulating the process of IS-induced ferroptosis in different glial cells. We then review recent therapies that leverage ferroptosis modulation for the treatment of IS. Extensive preclinical and clinical research is necessary to fully understand the roles of glia-neuron crosstalk and ferroptosis in IS.

[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.

Nrf2 and Ferroptosis: A New Research Direction for Ischemic Stroke.

Ischemic stroke (IS) is one of the leading causes of death and morbidity worldwide. As a novel form of cell death, ferroptosis is an important mechanism of ischemic stroke. Nuclear factor E2-related factor 2 (Nrf2) is the primary regulator of cellular antioxidant response. In addition to alleviating ischemic stroke nerve damage by reducing oxidative stress, Nrf2 regulates genes associated with ferroptosis, suggesting that Nrf2 may inhibit ferroptosis after ischemic stroke. However, the specific pathway of Nrf2 on ferroptosis in the field of ischemic stroke remains unclear. Therefore, this paper provides a concise overview of the mechanisms underlying ferroptosis, with a particular focus on the regulatory role of Nrf2. The discussion highlights the potential connections between Nrf2 and the mitigation of oxidative stress, regulation of iron metabolism, modulation of the interplay between ferroptosis and inflammation, as well as apoptosis. This paper focuses on the specific pathway of Nrf2 regulation of ferroptosis after ischemic stroke, providing scientific research ideas for further research on the treatment of ischemic stroke.

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.

[Observation and evaluation of the application effect of a dynamic scoring method in the emergency department of primary hospital].

OBJECTIVE: To establish a new emergency dynamic score (EDS) method based on modified early warning score (MEWS) combined with clinical symptoms, rapidly available examination results and bedside examination data in the emergency department, and to observe its applicability and feasibility in the clinical application of emergency department. METHODS: A total of 500 patients admitted to the department of emergency of Xing'an County People's Hospital from July 2021 to April 2022 were selected as research objects. After admission, EDS and MEWS scores were performed first, and then acute physiology and chronic health evaluation II (APACHE II) was performed retrospectively, and the prognosis of patients was followed up. The difference of short-term mortality in patients with different score segments of EDS, MEWS and APACHE II were compared. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the prognostic value of various scoring methods in critically ill patients. RESULTS: The mortality of patients in different score groups of each scoring method increased with the increase of the score value [The mortality of 0-1, 2-3, 4-5, 6-7 and ≥ 8 of MEWS were 1.9% (3/159), 2.9% (6/208), 12.4% (11/89), 29.0% (9/31) and 61.5% (8/13), respectively. The mortality of EDS stage 1 weighted MEWS score 0-3, 4-6, 7-9, 10-12 and ≥ 13 were 0 (0/49), 3.2% (8/247), 6.6% (10/152), 31.9% (15/47) and 80.0% (4/5), respectively. The mortality of EDS stage 2 clinical symptom score 0-4, 5-9, 10-14, 15-19, ≥ 20 were 0 (0/13), 0.4% (1/235), 3.6% (6/165), 26.2% (17/65), 59.1% (13/22), respectively. The mortality of EDS stage 3 rapid test data score 0-6, 7-12, 13-18, 19-24 and ≥ 25 were 0 (0/16), 0.6% (1/159), 4.6% (6/131), 13.7% (7/51) and 65.0% (13/20), respectively. The mortality of patients with APACHE II score 0-6, 7-12, 13-18, 19-24 and ≥ 25 were 1.9% (1/53), 0.4% (1/277), 4.6% (5/108), 34.2% (13/38) and 70.8% (17/24), respectively, all P < 0.01]. When the MEWS score was more than 4, the specificity was 87.0%, the sensitivity was 67.6%, and the maximum Youden index was 0.546, which was the best cut-off point. When the weighted MEWS score of EDS in the first stage was greater than 7, the specificity of predicting the prognosis of patients was 76.2%, the sensitivity was 70.3%, and the maximum Youden index was 0.465, which was the best cut-off point. When clinical symptom score of EDS in the second stage was more than 14, the specificity and sensitivity of predicting the prognosis of patients were 87.7% and 81.1%, respectively, and the maximum Youden index was 0.688, which was the best cut-off point. When the third stage rapid test of EDS reached 15 points, the specificity of predicting the prognosis of patients was 70.9%, and the sensitivity was 96.3%, and the maximum Youden index was 0.672, which was the best cut-off point. When APACHE II score was higher than 16, the specificity was 87.9%, the sensitivity was 86.5%, and the maximum Youden index was 0.743, which was the best cut-off point. ROC curve analysis showed that: EDS score in the stage 1, 2 and 3, MEWS score and APACHE II score can predict the short-term mortality risk of critically ill patients. The area under the ROC curve (AUC) and 95% confidence interval (95%CI) were 0.815 (0.726-0.905), 0.913 (0.867-0.959), 0.911 (0.860-0.962), 0.844 (0.755-0.933) and 0.910 (0.833-0.987), all P < 0.01. In terms of the differential ability to predict the risk of death in the short-term, the AUC in the second and third stages of EDS were highly close to APACHE II score (0.913, 0.911 vs. 0.910), and significantly higher than MEWS score (0.913, 0.911 vs. 0.844, both P < 0.05). CONCLUSIONS: EDS method can dynamically evaluate emergency patients in stages, and has the characteristics of fast, simple, easy to obtain test and inspection data, which can facilitate emergency doctors to evaluate emergency patients objectively and quickly. It has strong ability to predict the prognosis of emergency patients, and is worth popularizing in emergency departments of primary hospitals.

[Tiaoshen Jieyu acupuncture combined with sertraline hydrochloride tablet for post-stoke depression: a randomized controlled trial].

OBJECTIVE: To compare the clinical efficacy between Tiaoshen Jieyu acupuncture (acupuncture for regulating mind and relieving depression) combined with sertraline hydrochloride tablet and simple sertraline hydrochloride tablet for post-stroke depression (PSD). METHODS: A total of 76 patients with PSD were randomized into an observation group (38 cases, 6 cases dropped off) and a control group (38 cases, 4 cases dropped off). Both groups were treated with conventional treatment i.e. controlling blood pressure and anti-inflammation. Sertraline hydrochloride tablet was given orally in the control group, 20 mg a time, once a day. On the basis of the treatment in the control group, Tiaoshen Jieyu acupuncture was applied at Baihui (GV 20), Yintang (GV 24+), Neiguan (PC 6), Taichong (LR 3), etc. in the observation group, Baihui (GV 20) and Yintang (GV 24+) were connected to electroacupuncture, with disperse-dense wave, 2 Hz/100 Hz in frequency, 30 min a time, once a day, 6 times a week. Treatment of 8 weeks was required in both groups. Before and after treatment, the scores of Hamilton depression scale (HAMD), National Institutes of Health stroke scale (NIHSS), Barthel index (BI) and Pittsburgh sleep quality index (PSQI) were observed respectively, the therapeutic efficacy and rate of adverse reactions were evaluated in the two groups. RESULTS: After treatment, the scores of HAMD, NIHSS and PSQI were lower while BI scores were higher than those before treatment in both groups (P<0.05); the scores of HAMD, NIHSS and PSQI in the observation group were lower while BI score was higher than those in the control group (P<0.05). The total effective rate was 93.8% (30/32) in the observation group, which was higher than 70.6% (24/34) in the control group (P<0.05). The rate of adverse reactions was 9.4% (3/32) in the observation group, which was lower than 32.4% (11/34) in the control group (P<0.05). CONCLUSION: Tiaoshen Jieyu acupuncture combined with sertraline hydrochloride tablet can improve the depression degree, neurological function, activity of daily living and sleep quality in patients with post-stroke depression, the clinical efficacy is superior to simple sertraline hydrochloride, and can alleviate the adverse reactions caused by medication.

[Effect of different electrical current intensities of electroacupuncture preconditioning on cardiac function and macrophage polarization in mice with acute myocardial ischemia].

OBJECTIVE: To observe the effect of different intensities of electroacupuncture (EA) preconditioning on car-diac function and polarization state of macrophages in mice with acute myocardial ischemia (AMI), so as to explore its possible mechanism underlying improvement of AMI. METHODS: A total of 50 male C57BL/6J mice were randomly divided into sham ope-ration, AMI model, and EA pretreatment groups (0.5 mA, 1 mA, 3 mA subgroups), with 10 mice in each group/subgroup. The mice in the EA pretreatment groups were subjected to EA stimulation of bilateral "Neiguan"(PC6) with 0.5, 1.0 and 3 mA respectively and frequency of 2 Hz/15 Hz for 20 min, once a day, for 3 days. The acute myocardial ischemia model was established by ligating the anterior descending branch (ADB) of the left coronary artery, while the sham operation only had a surgical suture trans-passed below the ADB but without ligation. The myocardial infarction area was measured after TTC staining, and the cardiac function ï¼»left ventricular ejection fraction (EF), short-axis contraction rate (FS)ï¼½ was detected by using echocardiography. The M1 macrophages were labeled with CD11b+F480+CD206low, M2 macrophages were labeled with CD11b+F480+CD206high and detected by using flow cytometry, and the expression levels of myocardial interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), Toll-like receptor-4 (TLR4) proteins were detected by using Western blot. RESULTS: Compared with the sham operation group, the model group had a significant increase in the infarction area (P<0.000 1), number of cardiac macrophages and percentage of M1 type macrophages (P<0.000 1), and the expression levels of myocardial IL-1ß, TNF-α, TLR4 proteins (P<0.001, P<0.01), and a remarkable decrease in the levels of EF, FS and the percentage of M2 type macrophages (P<0.000 1). In contrast to those of the model group, the area of myocardial infarction (P<0.000 1, P<0.01), expression levels of myocardial IL-1ß, TNF-α, TLR4 proteins (P<0.01, P<0.05, P<0.001) in the 0.5 mA, 1 mA and 3 mA groups, number of macrophages and percentage of M1 macrophages (P<0.05) in the 1 mA group were significantly decreased, while the levels of EF and FS (P<0.000 1, P<0.05, P<0.001) in the 3 EA groups, and percentage of M2 macrophage (P<0.05) in the 1 mA group were significantly increased. Comparison among the 3 EA groups displayed that the effects of 1 mA group were significantly superior to those of 0.5 and 3 mA groups in up-regulating EF and FS (P<0.01, P<0.001), and in down-regulating the area of infarct myocardium (P<0.01, P<0.000 1), and the expression of TLR4 protein (P<0.01), and 0.5 mA group in the expression of IL-1ß and TNF-α proteins (P<0.05). CONCLUSION: EA preconditioning with electrical current intensities of 0.5 mA, 1 mA and 3 mA can effectively reduce myocardial infarction size, improve cardiac function in mice with AMI, which may be related with its effects in reducing the number of cardiac macrophages and down-regulating the expression of myocardial IL-1ß, TNF-α and TLR4 proteins. The therapeutic effect of 1 mA is better than that of 0.5 and 3 mA.

Electro-acupuncture Promotes Angiogenesis via Exosomal miR-210 in the Hypoxia-induced HUVECs Mediated HIF-1α/VEGF/Notch 1 Signal Pathway.

BACKGROUND: Acupuncture has been wildly applied for cerebral ischemia treatment in China for thousands of years, while the specific mechanism remains uncertain. Recently, many studies have shown that acupuncture promotes angiogenesis after ischemia occurs. Here, we examined the effect of electro-acupuncture (EA) exosomes on angiogenesis in hypoxia-induced human umbilical vein endothelial cells (HUVECs). OBJECTIVE: To investigate whether EA exosomal miR-210 promotes angiogenesis in the hypoxiainduced HUVECs via the HIF-1α/VEGF/Notch 1 signal pathway. METHODS: The middle cerebral artery occlusion (MCAO) model was established and treated with EA therapy. Then, exosomes were identified and isolated from rats' plasma in the MCAO+EA group by transmission electron microscopy (TEM), surface markers expressions, and PKH26 reagent. MiR- 210 mimic, miR-210 inhibitor, and HIF-1α were transfected. Flow cytometry, CCK-8 assay, and Transwell assay were conducted to assess the migration, apoptosis, and proliferation of each group of cells. Western blot and quantitative PCR were performed to detect the CD34, HIF-1α, VEGF, Notch 1, and miR-210 expression levels in each group. RESULTS: MiR-210 was significantly upregulated in exosomes of the MCAO plasma, and further enhanced by EA therapy. EA-EXOs and miR-210 mimic inhibited cell apoptosis, promoted cell proliferation and cell migration in hypoxia-induced HUVECs. However, the miR-210 inhibitor reversed the proliferation and migration number induced by EA-EXOs. Besides, EA-EXOs and miR- 210 mimic further enhanced those HIF-1α, VEGF, and Notch 1 levels compared to the hypoxia treatment only. Silencing HIF-1α or miR-210 reversed the high expressions of those three angiogenic factors induced by hypoxia and EA-EXO. qPCR showed similar trends with their relative mRNAs. To analyze these associations quantificationally, Spearman's rank correlation coefficient was calculated. As revealed by results, the expression of proteins and mRNA were highly correlative with each other. CONCLUSION: These results indicated that EA-EXO miR-210 promotes angiogenesis in hypoxia conditions via HIF-1α/VEGF/Notch 1 signal pathway.

[Electroacupuncture for acute ischemic stroke and its effect on plasma levels of IL-17 and IL-10].

OBJECTIVE: To compare the clinical efficacy on acute ischemic stroke (AIS) between electroacupuncture combined with conventional western medicine therapy and simple conventional western medicine therapy and its effect on plasma levels of interleukin (IL)-17 and IL-10. METHODS: A total of 60 patients with AIS were randomized into an observation group (30 cases, 2 cases dropped off) and a control group (30 cases, 4 cases dropped off). The control group was treated with conventional western medicine therapy i.e neuroprotection and cerebral circulation improvement. On the basis of the treatment in the control group, in the observation group, acupuncture was applied at Baihui (GV 20), Yintang (GV 24+) and Quchi (LI 11), Zusanli (ST 36), Sanyinjiao (SP 6), etc. on the affected side, Baihui (GV 20)-Yintang (GV 24+), Quchi (LI 11)-Hegu (LI 4) and Zusanli (ST 36)-Sanyinjiao (SP 6) were connected with electroacupuncture, with disperse-dense wave, 2 Hz/15 Hz in frequency, once a day for consecutive 10 days. Before and after treatment, the scores of National Institution of Health stroke scale (NIHSS) and modified Barthel index (MBI) were observed, plasma levels of IL-17 and IL-10 were detected by ELISA method. RESULTS: After treatment, NIHSS scores were decreased while MBI scores were increased compared before treatment in both groups (P<0.01); compared with the control group, NIHSS score was decreased while MBI score was increased in the observation group (P<0.05). After treatment, IL-17 levels were decreased while IL-10 levels were increased compared before treatment in both groups (P<0.01); compared with the control group, IL-17 level was decreased while IL-10 level was increased in the observation group (P<0.05). CONCLUSION: Electroacupuncture combined with conventional western medinice therapy can improve the nerve function and activity of daily living in patients with AIS, its clinical efficacy is superior to simple conventional western medicine therapy, the mechanism may relate to the regulation on IL-17/IL-10 imbalance.

Altered Brain Function Activity in Patients With Dysphagia After Cerebral Infarction: A Resting-State Functional Magnetic Resonance Imaging Study.

Objective: Dysphagia after cerebral infarction (DYS) has been detected in several brain regions through resting-state functional magnetic resonance imaging (rs-fMRI). In this study, we used two rs-fMRI measures to investigate the changes in brain function activity in DYS and their correlations with dysphagia severity. Method: In this study, a total of 22 patients with DYS were compared with 30 patients without dysphagia (non-DYS) and matched for baseline characteristics. Then, rs-fMRI scans were performed in both groups, and regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuation (fALFF) values were calculated in both groups. The two-sample t-test was used to compare ReHo and fALFF between the groups. Pearson's correlation analysis was used to determine the correlations between the ReHo and fALFF of the abnormal brain regions and the scores of the Functional Oral Intake Scale (FOIS), the Standardized Bedside Swallowing Assessment (SSA), the Videofluoroscopic Swallowing Study (VFSS), and the Penetration-Aspiration Scale (PAS). Results: Compared with the non-DYS group, the DYS group showed decreased ReHo values in the left thalamus, the left parietal lobe, and the right temporal lobe and significantly decreased fALFF values in the right middle temporal gyrus and the inferior parietal lobule. In the DYS group, the ReHo of the right temporal lobe was positively correlated with the SSA score and the PAS score (r = 0.704, p < 0.001 and r = 0.707, p < 0.001, respectively) but negatively correlated with the VFSS score (r = -0.741, p < 0.001). The ReHo of the left parietal lobe was positively correlated with SSA and PAS (r = 0.621, p = 0.002 and r = 0.682, p < 0.001, respectively) but negatively correlated with VFSS (r = -0.679, p = 0.001). Conclusion: The changes in the brain function activity of these regions are related to dysphagia severity. The DYS group with high ReHo values in the right temporal and left parietal lobes had severe dysphagia.

Reconstruction of Tumor-Induced Pelvic Defects With Customized, Three-Dimensional Printed Prostheses.

Background: Reconstruction of pelvis girdle stability after tumor-induced hemipelvectomy remains challenging. We surgically treated 13 patients with custom-made, three-dimensional printed hemipelvic prostheses. We aim to identify the preliminary outcomes for patients who have been managed with more mixed regions of prosthetic pelvic reconstruction and the feasibility of two reconstructive systems. Methods: Seven male patients and 6 female patients treated at our center between January 2019 and May 2021 were included. There were 11 primary sarcomas and 2 solitary bone metastases. After en bloc tumor resection, two types of personalized, three-dimensional printed prostheses were fixed to restore the stability and rebuild the load transfer. The position of the reconstructed hemipelvis was evaluated on an anteroposterior plain radiograph. The complications and outcomes were traced. One amputation specimen was discovered through histological analysis of the porous structure. Results: The operative duration was 467 ± 144 min, and the blood loss was 3,119 ± 662 ml. During a follow-up of 22.4 ± 8.5 months, two patients had delayed wound healing and one had a second-stage flap transfer. One patient with osteosarcoma died of pulmonary metastasis 27 months after surgery. Two patients with marginal resection suffered from local recurrence and had extra surgeries. One patient had traumatic hip dislocation 2 months after surgery and manipulative reduction was performed. The acetabular inclination of the affected side was 42.2 ± 4.3°, compared with 42.1 ± 3.9° on the contralateral side. The horizontal distance between the center of the femoral head and the middle vertical line was 10.4 ± 0.6 cm, while the reconstructed side was 9.8 ± 0.8 cm. No significant difference in acetabular position after surgery was found (p > 0.05). The amputation specimen harvested from one patient with local recurrence demonstrated bone and soft tissue ingrowth within the three-dimensional printed trabecular structure. Walking ability was preserved in all patients who are still alive and no prosthesis-related complications occurred. The MSTS score was 22.0 ± 3.7. Conclusions: Both types of custom-made, three-dimensional printed prostheses manifested excellent precision, mechanical stability, and promising functional rehabilitation. The porous structure exhibited favorable histocompatibility to facilitate the ingrowth of bone and soft tissue.

Electroacupuncture Attenuates Post-Inflammatory IBS-Associated Visceral and Somatic Hypersensitivity and Correlates With the Regulatory Mechanism of Epac1-Piezo2 Axis.

Electroacupuncture (EA) is considered to have a therapeutic effect in the relief of irritable bowel syndrome (IBS)-associated visceral hypersensitivity via the reduction of the level of 5-hydroxytryptamine (5-HT) and 5-HT3 receptors (5-HT3R). However, whether Epac1/Piezo2, as the upstream of 5-HT, is involved in this process remains unclear. We investigated whether EA at the ST36 and ST37 acupoints alleviated visceral and somatic hypersensitivity in a post-inflammatory IBS (PI-IBS) model mice via the Epac1-Piezo2 axis. In this study, we used 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced PI-IBS as a mouse model. Visceral sensitivity was assessed by the abdominal withdrawal reflex test. Somatic sensitivity was evaluated by the hind paw withdrawal threshold. Quantitative real-time PCR, immunofluorescence staining, ELISA, and Western blotting were performed to examine the expressions of Epac1, Piezo2, 5-HT, and 5-HT3R from the mouse distal colon/L5-S2 dorsal root ganglia (DRG). Our results showed that EA improved the increased visceral sensation and peripheral mechanical hyperalgesia in PI-IBS model mice, and the effects of EA were superior to the sham EA. EA significantly decreased the protein and mRNA levels of Epac1 and Piezo2, and reduced 5-HT and 5-HT3R expressions in the distal colon. Knockdown of colonic Piezo2 eliminated the effect of EA on somatic hypersensitivity. Combined knockdown of colonic Epac1 and Piezo2 synergized with EA in relieving visceral hypersensitivity and blocked the effect of EA on somatic hypersensitivity. Additionally, protein levels of Epac1 and Piezo2 were also found to be decreased in the L5-S2 DRGs after EA treatment. Taken together, our study suggested that EA at ST36 and ST37 can alleviate visceral and somatic hypersensitivity in PI-IBS model mice, which is closely related to the regulation of the Epac1-Piezo2 axis.

Sulphidisation of oxides and oxidised sulphides and adsorption of thiol collectors on the sulphidised products-a critical review.

Sulphidisation, an electrochemical process for conversion of a non-sulphide, oxide or oxidised sulphide, to a sulphide surface that facilitates efficient adsorption of thiol collectors to impart hydrophobicity, offers a way to improve the enrichment of oxide and oxidised sulphide ores by flotation. Although it has shown great potential, it has equally proved to suffer from drawbacks such as low efficiency, difficulty to sulphidise minerals that are prone to surface oxidation and the chemistry at play remains insufficiently understood. These drawbacks hinder the full potential of the sulphidisation process as a remediation strategy for flotation of oxide and oxidised sulphide ores. A holistic understanding of the process is crucial in identification of the underpinning phenomena that render the process inefficient and will be a stepping stone in the quest to modify it for an improved efficiency. Therefore, this paper seeks to review the sulphidisation reactions and products at the mineral-solution interfaces of oxide and oxidised sulphide minerals. The influence and implications of the sulphidisation conditions on adsorption of thiol collectors on mineral surfaces to impart hydrophobicity necessary for flotation are also highlighted. Finally, it makes recommendations on how to circumvent the drawbacks and provides guidelines for future research and industrial application.

DBFU-Net: Double branch fusion U-Net with hard example weighting train strategy to segment retinal vessel.

Background: Many fundus imaging modalities measure ocular changes. Automatic retinal vessel segmentation (RVS) is a significant fundus image-based method for the diagnosis of ophthalmologic diseases. However, precise vessel segmentation is a challenging task when detecting micro-changes in fundus images, e.g., tiny vessels, vessel edges, vessel lesions and optic disc edges. Methods: In this paper, we will introduce a novel double branch fusion U-Net model that allows one of the branches to be trained by a weighting scheme that emphasizes harder examples to improve the overall segmentation performance. A new mask, we call a hard example mask, is needed for those examples that include a weighting strategy that is different from other methods. The method we propose extracts the hard example mask by morphology, meaning that the hard example mask does not need any rough segmentation model. To alleviate overfitting, we propose a random channel attention mechanism that is better than the drop-out method or the L2-regularization method in RVS. Results: We have verified the proposed approach on the DRIVE, STARE and CHASE datasets to quantify the performance metrics. Compared to other existing approaches, using those dataset platforms, the proposed approach has competitive performance metrics. (DRIVE: F1-Score = 0.8289, G-Mean = 0.8995, AUC = 0.9811; STARE: F1-Score = 0.8501, G-Mean = 0.9198, AUC = 0.9892; CHASE: F1-Score = 0.8375, G-Mean = 0.9138, AUC = 0.9879). Discussion: The segmentation results showed that DBFU-Net with RCA achieves competitive performance in three RVS datasets. Additionally, the proposed morphological-based extraction method for hard examples can reduce the computational cost. Finally, the random channel attention mechanism proposed in this paper has proven to be more effective than other regularization methods in the RVS task.

The Angiogenesis Effects of Electro-acupuncture Treatment via Exosomal miR-210 in Cerebral Ischemia-Reperfusion Rats.

BACKGROUND: Acupuncture has been recommended as an alternative and complementary therapy for preventing and treating cerebral ischemia by the World Health Organization (WHO) for years. However, the mechanisms remain unclear. Accumulating evidence has shown that acupuncture can promote angiogenesis to attenuate brain damage after ischemic stroke. In recent years, exosome- carried microRNAs (miRNAs) activated by acupuncture have proven effective in regulating pathological changes. We, therefore, investigated whether electro-acupuncture (EA) enhanced angiogenesis in cerebral stroke via exosome-carried miR-210. METHODS: We extracted and identified the exosomes from the serum of MCAO with EA treatment and injected them into MCAO rats for further observation. Simultaneously, miR-120 siRNA and HIF-1α inhibitor were transfected. Then, we evaluated the volume of infarction, pathological changes, and expression levels of angiogenic related factors of each group of rats by TTC and HE staining, transmission electron microscope (TEM), western blot, and quantitative PCR (qPCR). RESULTS: Compared with the MCAO group, EA-Exosome (EA-EXO) treatment significantly decreased the infarct volume and the pathological damage, but miR-210 siRNA or HIF-1α inhibitor reversed the protective outcomes induced by EA-EXO. Moreover, EA-EXO treatment upregulated miR-210 and increased CD34, HIF-1α, VEGF, Notch1 protein, and mRNA expressions compared to the MCAO group. MiR-210 siRNA or HIF-1α inhibitor treatments both down-regulated those angiogenic related proteins and mRNAs. CONCLUSION: EA treatment could activate the HIF-1α/VEGF/Notch 1 signal pathway to facilitate angiogenesis after ischemic stroke via exosomal miR-210.