Effects of electroacupuncture on postoperative cognitive dysfunction and its underlying mechanisms: a literature review of rodent studies.

With the aging of the population, the health of the elderly has become increasingly important. Postoperative cognitive dysfunction (POCD) is a common neurological complication in elderly patients following general anesthesia or surgery. It is characterized by cognitive decline that may persist for weeks, months, or even longer. Electroacupuncture (EA), a novel therapy that combines physical nerve stimulation with acupuncture treatment from traditional Chinese medicine, holds potential as a therapeutic intervention for preventing and treating POCD, particularly in elderly patients. Although the beneficial effects of EA on POCD have been explored in preclinical and clinical studies, the reliability of EA is limited by methodological shortcomings, and the underlying mechanisms remain largely unexplored. Therefore, we have synthesized existing evidence and proposed potential biological mechanisms underlying the effects of EA on neuroinflammation, oxidative stress, autophagy, the microbiota-gut-brain axis, and epigenetic modification. This review summarizes recent advances in EA and POCD, provides a theoretical foundation, explores potential molecular mechanisms for the prevention and treatment of POCD, and offers a basis for conducting relevant clinical trials.

Optimization of Ethanol Extraction Technology for Yujin Powder Using Response Surface Methodology with a Box-Behnken Design Based on Analytic Hierarchy Process-Criteria Importance through Intercriteria Correlation Weight Analysis and Its Safety Evaluation.

Here, we aimed to optimize the ethanol extraction technology for Yujin powder (YJP) and evaluate its safety. The ultrasonic-assisted ethanol reflux extraction method refluxing was used to extract YJP. The parameters were optimized through a combination of single-factor and response surface methodology (RSM). The comprehensive Y value score calculated using the content of 13 active ingredients in YJP ethanolic extracts (YEEs) and the yield of the dry extract were used as measuring criteria. RSM with a Box-Behnken design using three factors and three levels was adopted to optimize the ethanol extraction technology for YJP. Finally, acute and subchronic toxicity tests were performed to evaluate its safety. The results revealed the best technological parameters: a liquid-material ratio of 24:1, an ethanol concentration of 69%, assistance of ultrasound (40 °C, 50 kHZ, 30 min), reflux time of 53 min, and reflux temperature of 50 °C. In acute toxicity tests, the maximum administration dosage in mice was 28.21 g/kg, which is higher than 10 times the clinical dosage. Adverse effects in the acute and subchronic toxicity tests were not observed. All clinical indexes were normal. In conclusion, the RSM based on AHP-CRITIC weight analysis could be used to optimize the ethanol extraction technology for YJP and YEEs prepared under the above conditions and ensure high safety.

Exploration of the Potential Mechanism of Yujin Powder treating Dampness-heat Diarrhea by Integrating UPLC-MS/MS and Network Pharmacology Prediction.

BACKGROUND: Yujin powder (YJP) is a classic prescription for treating dampness-heat diarrhea (DHD) in Traditional Chinese Medicine (TCM), but the main functional active ingredients and the exact mechanisms have not been systematically studied. OBJECTIVES: This study aimed to preliminarily explore the potential mechanisms of YJP for treating DHD by integrating UPLC-MS/MS and network pharmacology methods. METHODS: Ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technology was used to determine the ingredients of YJP. And then, the targets of these components were predicted and screened from TCMSP, SwissTargetPrediction databases. The disease targets related to DHD were obtained by using the databases of GeneCards, OMIM, DisGeNET, TTD, and DrugBank. The protein-protein interaction networks (PPI) of YJP-DHD were constructed using the STRING database and Origin 2022 software to identify the cross-targets by screening the core-acting targets and a network diagram by Cytoscape 3.8.2 software was also constructed. Metascape database was used for performing GO and KEGG enrichment anlysis on the core genes. Finally, molecular docking was used to verify the results with AutoDock 4.2.6, AutoDock Tools 1.5.6, PyMOL 2.4.0, and Open Babel 2.3.2 software. RESULTS: 597 components in YJP were detected, and 153 active components were obtained through database screening, among them the key active ingredients include coptisine, berberine, baicalein, etc. There were 362 targets treating DHD, among them the core targets included TNF, IL-6, ALB, etc. The enriched KEGG pathways mainly involve PI3K-Akt, TNF, MAPK, etc. Molecular docking results showed that coptisine, berberine, baicalein, etc., had a strong affinity with TNF, IL-6, and MAPK14. Therefore, TNF, IL-6, MAPK14, ALB, etc., are the key targets of the active ingredients of YJP coptisine, baicalein, and berberine, etc. They have the potential to regulate PI3K-Akt, MAPK, and TNF signalling pathways. The component-target-disease network diagram revealed that YJP treated DHD through the effects of anti-inflammation, anti-diarrhea, immunoregulation, and improving intestinal mucosal injury. CONCLUSION: It is demonstrated that YJP treats DHD mainly through the main active ingredients coptisine, berberine, baicalein, etc. comprehensively exerting the effects of anti-inflammation, anti-diarrhea, immunoregulation, and improving intestinal mucosal injury, which will provide evidence for further in-depth studying the mechanism of YJP treating DHD.

Synergistic therapeutic effect of nanomotors triggered by Near-infrared light and acidic conditions of tumor.

Due to the complexity of tumors, multimodal therapy for them has always been of concern to researchers. How to design a multifunctional drug nanoplatform with cascade effect and capable of responding to specific stimuli in the tumor microenvironment is the key to achieve efficient multimodal synergistic therapy of cancer. Here, we prepare a kind of GNRs@SiO2@PDA-CuO2-l-Arg (GSPRs-CL) nanomotors for systematic treatment of tumor. First, under near-infrared (NIR) irradiation, GSPRs-CL can generate heat and exhibit excellent photothermal therapy effect. Then under acidic conditions, CuO2 can be decomposed to release Cu2+ and generate H2O2, which not only complemented the limited endogenous H2O2 in cells, but also further triggered Fenton-like reaction, converting H2O2 into •OH to kill cancer cells, thereby achieving chemodynamic therapy. Furthermore, both endogenous and exogenous H2O2 can release nitric oxide (NO) in response to the occurrence of l-Arg of nanomotors to enhance gas therapy. In addition, as a dual-mode drive, NIR laser and NO can promote the penetration ability of nanomotors at tumor sites. The experimental results in vivo show that the drug nanoplatform had good biosafety and significant tumor killing effect triggered by NIR light and acidic conditions of tumor. It provide a promising strategy for the development of advanced drug nanoplatform for cancer therapy.

Hypothermic neuroprotection by targeted cold autologous blood transfusion in a non-human primate stroke model.

Over decades, nearly all attempts to translate the benefits of therapeutic hypothermia in stroke models of lower-order species to stroke patients have failed. Potentially overlooked reasons may be biological gaps between different species and the mismatched initiation of therapeutic hypothermia in translational studies. Here, we introduce a novel strategy of selective therapeutic hypothermia in a non-human primate ischemia-reperfusion model, in which autologous blood was cooled ex vivo and the cool blood transfusion was administered at the middle cerebral artery just after the onset of reperfusion. Cold autologous blood cooled the targeted brain rapidly to below 34 °C while the rectal temperature remained around 36 °C with the assistance of a heat blanket during a 2-h hypothermic process. Therapeutic hypothermia or extracorporeal-circulation related complications were not observed. Cold autologous blood treatment reduced infarct sizes, preserved white matter integrity, and improved functional outcomes. Together, our results suggest that therapeutic hypothermia, induced by cold autologous blood transfusion, was achieved in a feasible, swift, and safe way in a non-human primate model of stroke. More importantly, this novel hypothermic approach conferred neuroprotection in a clinically relevant model of ischemic stroke due to reduced brain damage and improved neurofunction. This study reveals an underappreciated potential for this novel hypothermic modality for acute ischemic stroke in the era of effective reperfusion.

Biodegradable CuMoO4 Nanodots with Multienzyme Activities for Multimodal Treatment of Tumor.

Due to their complexity and variability, tumors need to be treated with multimodal combined therapy, which requires the development of therapeutic agents that can provide multimodal therapeutic effects. Herein, CuMoO4 nanodots smaller than 10 nm that can be prepared by simple hydrothermal method are reported. These nanodots can be well dispersed in water and have good biosafety and biodegradability. Further studies show that these nanodots also present multienzyme activities, such as catalase, peroxidase and glutathione peroxidase. In addition, CuMoO4 nanodots exhibit high photothermal conversion efficiency (41%) under 1064 nm near-infrared laser irradiation. In vitro and in vivo experimental results indicate that CuMoO4 nanodots can effectively inhibit the instinctive regulation of tumor cells to oxidative stress, provide sustained treatment to achieve photothermal synergistic ferroptosis, and trigger immune responses to immunogenic cell death. It is worth mentioning that the CuMoO4 nanodots also cause cuproptosis of tumor cells. This study provides a promising nanoplatform for multimodal combined therapy of cancer.

Triage Nurse-Activated Emergency Evaluation Reduced Door-to-Needle Time in Acute Ischemic Stroke Patients Treated with Intravenous Thrombolysis.

Methods: This was a retrospective analysis in a general hospital emergency department in Beijing, China. 212 adult AIS patients treated with thrombolysis who failed to use EMSs were included. In addition to DNT, door-to-vein open time (DVT), door-to-blood sample deliver time (DBT), and 7-day NIHSS scores were evaluated. Results: 137 (64.6%) patients were in the triage nurse-activated group and 75 (35.4%) patients were in the doctor-activated group. The DNT of the triage nurse-activated group was significantly reduced compared with the doctor-activated group (28 (26, 32.5) min vs. 30 (28, 40) min, p=0.001). DNT less than 45 min was seen in 95.6% of patients in the triage nurse-activated group and 84% of patients in the doctor-activated group (p=0.011, OR 3.972, 95% CI 1.375-11.477). In addition, DVT (7 (4, 10) min vs. 8 (5, 12) min, P=0.025) and DBT (15 (13, 21) min vs. 19 (15, 26) min, p=0.001) of the triage nurse-activated group were also shorter than those of the doctor-activated group (p < 0.05). The 7-day NIHSS scores were not statistically different between the two groups. Conclusions: Triage nurse-activated urgent emergency evaluation could reduce the door-to-needle time, which provides a feasible opportunity to optimize the emergency department service for AIS patients who failed to use emergency medical services.

Doxorubicin-Loaded Walnut-Shaped Polydopamine Nanomotor for Photothermal-Chemotherapy of Cancer.

The combination of photothermal therapy and chemical drug therapy shows good prospects in cancer treatment, but there are also some limitations such as low permeability of therapeutic agents and uneven photothermal therapy. Here, we synthesized a walnut-shaped polydopamine (PDA) nanomotor driven by near infrared (NIR) light. The nanomotor was modified by methoxy polyethylene glycol amine (mPEG-NH2) for improving water solubility. PDA-PEG loaded adriamycin through π-π accumulation and hydrogen bonding. The experimental results showed that the PDA nanomotors had good biocompatibility and photothermal effect. Further, the NIR light irradiation and tumor cell microenvironment are conducive to drug release. In addition, under the irradiation of an NIR laser, the asymmetry of walnut-shaped nanoparticles makes the particles obtain the ability of autonomous movement, which can improve the permeability of particles in 3D tumor balls, which can provide support for drug penetration and heat dispersion. This strategy offers potential innovative materials for photothermal/chemotherapy synergistic therapy of tumors.

Systematic Understanding of Mechanism of Danggui Shaoyao San against Ischemic Stroke Using a Network Pharmacology Approach.

PURPOSE: Danggui Shaoyao San (DSS) was developed to treat the ischemic stroke (IS) in patients and animal models. The purpose of this study was to explore its active compounds and demonstrate its mechanism against IS through network pharmacology, molecular docking, and animal experiment. METHODS: All the components of DSS were retrieved from the pharmacology database of TCM system. The genes corresponding to the targets were retrieved using OMIM, CTD database, and TTD database. The herb-compound-target network was constructed by Cytoscape software. The target protein-protein interaction network was built using the STRING database. The core targets of DSS were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Then, we achieved molecular docking between the hub proteins and the key active compounds. Finally, animal experiments were performed to verify the core targets. Triphenyltetrazolium chloride (TTC) staining was used to calculate the infarct size in mice. The protein expression was determined using the Western blot. RESULTS: Compound-target network mainly contained 51 compounds and 315 corresponding targets. Key targets contained MAPK1, SRC, PIK3R1, HRAS, AKT1, RHOA, RAC1, HSP90AA1, and RXRA FN1. There were 417 GO items in GO enrichment analysis (p < 0.05) and 119 signaling pathways (p < 0.05) in KEGG, mainly including negative regulation of apoptosis, steroid hormone-mediated signaling pathway, neutrophil activation, cellular response to oxidative stress, and VEGF signaling pathway. MAPK1, SRC, and PIK3R1 docked with small molecule compounds. According to the Western blot, the expression of p-MAPK 1, p-AKT, and p-SRC was regulated by DSS. CONCLUSIONS: This study showed that DSS can treat IS through multiple targets and routes and provided new insights to explore the mechanisms of DSS against IS.

The effect of remote ischemic postconditioning on autonomic function in patients with acute ischemic stroke: A Randomized Controlled Trail.

OBJECTIVE: The evidence for the effect of remote ischemic postconditioning(RIpostC) on autonomic function in patients with acute ischemic stroke(AIS) is lacking and the neural mechanism underlying the protection of RIpostC remains speculative. This trial was aimed to evaluated the efficiency of RIpostC on autonomic function in AIS patients. DESIGN: One hundred and six AIS patients were included in this prospective, randomized, placebo-controlled trial. Patients in intervention group (n = 57) received 4 cycles of alternating inflation (cuff inflation to 200 mmHg) and deflation for 5 min on healthy upper arm once a day for 30 days. The control group underwent a sham inflation and deflation cycles. Autonomic function was evaluated by heart rate variability (HRV). RESULTS: All HRV parameters except for the ratio of low frequency to high frequency (P = 0.101) increased significantly with time (P < 0.001) in the two groups. The value of standard deviation of all normal R-R intervals(SDNN) and high frequency at day7 and day30 and the value of the percent of difference between adjacent normal R-R intervals (pNN50) at day 30 in RIpostC group was significantly higher than that of the sham-RIpostC group(P < 0.05). A significant time-by-group interaction was observed in SDNN、pNN50、and high frequency over time between two groups (P < 0.05). CONCLUSIONS: 30-day RIpostC could improve autonomic function in AIS patients through the enhancement of the total autonomic nerve activity and vagus nerve activity. The mechanism of RIpostC mediating autonomic function needs to be further investigated.

Local anesthesia vs general anesthesia during endovascular therapy for acute posterior circulation stroke.

OBJECTIVE: The optimal anesthetic approach during endovascular therapy (EVT) in acute stroke patients remains an area of uncertainty. We investigated the impact of different anesthetic approaches on the outcome of posterior circulation stroke (PCS) patients undergoing EVT. METHODS: For this observational study, we enrolled consecutive PCS patients who underwent EVT from December 2012 to December 2018, and compared functional outcomes at 90 days as well as long-term follow-up in patients treated under local anesthesia (LA) versus general anesthesia (GA). Multivariable logistic regression and propensity score matched analyses were conducted. RESULTS: Among the 183 patients included in this study, 71 patients (38.8%) received LA and 112 patients (61.2%) received GA. Median modified Rankin Scale score at 90 days was 4 (IQR, 2-6) in both groups (P = .956). No significant differences in the rates of functional independence and mortality at 90 days as well as long-term follow-up post intervention were observed between the two groups, and Kaplan-Meier survival analysis showed comparable long-term survival probabilities. Safety outcomes (including procedure-related complications and serious adverse events) did not differ between these patients. The anesthetic approach was neither associated with functional independence nor associated with mortality. Propensity score matched analysis indicated similar results. CONCLUSIONS: For PCS patients undergoing EVT, LA compared with GA does not seem to result in different functional outcomes and complications rates.

Tetraphenylene-Coated Near-Infrared Benzoselenodiazole Dye: AIE Behavior, Mechanochromism, and Bioimaging.

A D-π-A-π-D type of tetraphenylene-coating benzoselenodiazole fluorescence dye with near-infrared emission has been designed and constructed. This dye shows an obvious aggregation-induced-emission behavior. In the solid state, it exhibits a reversible mechanochromism with the changes of near-infrared emission. Furthermore, this dye can be used to track the lysosomes of living cells and images in vivo.

General anesthesia vs local anesthesia during mechanical thrombectomy in acute ischemic stroke.

OBJECTIVE: To investigate the effect of general anesthesia (GA) on functional outcomes and complications rates in acute ischemic stroke (AIS) patients treated with mechanical thrombectomy (MT) compared to the use of local anesthesia (LA) at the puncture site. METHODS: This observational study was based on a prospectively registry study. AIS patients underwent MT with GA or LA from January 2013 to October 2017 were included. The primary outcome was the modified Rankin Scale (mRS) score at 90 days post-intervention. Furthermore, we assessed the long-term outcome of these patients. Multivariable logistic regression analysis was conducted to adjust for confounders. RESULTS: We enrolled 187 AIS patients in this study, patients in GA group had a similar mRS score compared to LA group at 90 days (2 [IQR, 1-4] vs 2.5 [IQR, 1-4], P = .917). No differences were found in the rates of functional independence (mRS 0-2), no or minimal disability (mRS 0-1), and mortality (mRS 6) between the 2 groups at 90 days post-intervention as well as long-term follow-up. The procedure-related complications and serious adverse events were similar between the LA group and GA group (P > .05 each). In multivariable analysis, GA use was not associated with functional outcomes. CONCLUSION: AIS patients who received GA during MT had similar functional outcomes and complications rates compared to patients received LA.

A Randomized Trial of Chinese Diaoshi Jifa on Treatment of Dizziness in Meniere's Disease.

Background. Meniere's disease is characterized by refractory dizziness and hearing disturbance. We aimed to investigate the efficacy and tolerance of Diaoshi Jifa, a Chinese hand skill for treating dizziness in Meniere's disease. Methods. An open-labeled, randomized, controlled intervention trial was conducted. Twenty-seven patients diagnosed with Meniere's disease were randomly allocated to control group or experimental group. Both groups were assessed by DHI (dizziness handicap inventory (DHI)) questionnaire score before and within 24 hours of receiving treatment, respectively. Results. Twenty-six participants completed the study, and no adverse event was reported due to Diaoshi Jifa treatment. The difference in the DHI scores between baseline and posttreatment reached significant difference in both groups (63.88 ± 19.94 versus 10.25 ± 9.77 and 54.36 ± 17.97 versus 49.6 ± 20.50). Significant difference in DHI scores was observed between the two groups after treatment (10.25 ± 9.77 versus 49.6 ± 20.50). Further investigation of DHI subscales in the experimental group revealed significant improvement posttreatment in the physical domain, functional domain, and emotional domain. Although higher rate of improvement in the emotional domain compared to physical or functional domains was found, the difference was not statistically significant. Conclusions. Diaoshi Jifa might be a fast, effective, and well-tolerated method for alleviating dizziness in Meniere's disease.