Exosomes derived from human umbilical cord mesenchymal stem cells alleviate Parkinson's disease and neuronal damage through inhibition of microglia.

Microglia-mediated inflammatory responses have been shown to play a crucial role in Parkinson's disease. In addition, exosomes derived from mesenchymal stem cells have shown anti-inflammatory effects in the treatment of a variety of diseases. However, whether they can protect neurons in Parkinson's disease by inhibiting microglia-mediated inflammatory responses is not yet known. In this study, exosomes were isolated from human umbilical cord mesenchymal stem cells and injected into a 6-hydroxydopamine-induced rat model of Parkinson's disease. We found that the exosomes injected through the tail vein and lateral ventricle were absorbed by dopaminergic neurons and microglia on the affected side of the brain, where they repaired nigral-striatal dopamine system damage and inhibited microglial activation. Furthermore, in an in vitro cell model, pretreating lipopolysaccharide-stimulated BV2 cells with exosomes reduced interleukin-1ß and interleukin-18 secretion, prevented the adoption of pyroptosis-associated morphology by BV2 cells, and increased the survival rate of SH-SY5Y cells. Potential targets for treatment with human umbilical cord mesenchymal stem cells and exosomes were further identified by high-throughput microRNA sequencing and protein spectrum sequencing. Our findings suggest that human umbilical cord mesenchymal stem cells and exosomes are a potential treatment for Parkinson's disease, and that their neuroprotective effects may be mediated by inhibition of excessive microglial proliferation.

Expression of recombinant human Apolipoprotein A-IMilano in Nicotiana tabacum.

Apolipoprotein A-IMilano (Apo A-IMilano) is a natural mutant of Apolipoprotein. It is currently the only protein that can clear arterial wall thrombus deposits and promptly alleviate acute myocardial ischemia. Apo A-IMilano is considered as the most promising therapeutic protein for treating atherosclerotic diseases without obvious toxic or side effects. However, the current biopharmaceutical platforms are not efficient for developing Apo A-IMilano. The objectives of this research were to express Apo A-IMilano using the genetic transformation ability of N. tabacum. The method is to clone the coding sequence of Apo A-IMilano into the plant binary expression vector pCHF3 with a Flag/His6/GFP tag. The constructed plasmid was transformed into N. tabacum by a modified agrobacterium-mediated method, and transformants were selected under antibiotic stress. PCR, RT-qPCR, western blot and co-localization analysis was used to further verify the resistant N. tabacum. The stable expression and transient expression of N. tabacum were established, and the pure product of Apo A-IMilano was obtained through protein A/G agarose. The results showed that Apo A-IMilano was expressed in N. tabacum with a yield of 0.05 mg/g leaf weight and the purity was 90.58% ± 1.65. The obtained Apo A-IMilano protein was subjected to amino acid sequencing. Compared with the theoretical sequence of Apo A-IMilano, the amino acid coverage was 86%, it is also found that Cysteine replaces Arginine at position 173, which indicates that Apo A-IMilano, a mutant of Apo A-I, is accurately expressed in N. tabacum. The purified Apo A-IMilano protein had a lipid binding activity. The established genetic modification N. tabacum will provide a cost-effective system for the production of Apo A-IMilano. Regarding the rapid propagation of N. tabacum, this system provides the possibility of large-scale production and accelerated clinical translation of Apo A-IMilano.

Melatonin and melatonergic agents for the prevention of postoperative delirium: A meta-analysis of randomized placebo-controlled trials.

Studies on melatonin and melatonergic agents (MMA) for the prevention of postoperative delirium (POD) have produced inconsistent findings. We conducted a meta-analysis to assess the effect of perioperative MMA on the prevention for POD. This meta-analysis is registered in the PROSPERO (CRD42020164900). We searched PubMed, Embase, and Cochrane Library through August 1, 2020 to identify randomized placebo-controlled trials (RCTs) that assessed MMA for the prevention for POD in adult patients undergoing surgery. The primary outcome was POD. Relative risk (RR) with 95% confidence interval (CI) was pooled using a random-effects model. Nine RCTs with 1452 patients were included. The incidence of POD was 23.8% (173/726) and 24.4% (177/726) in the MMA and placebo groups, respectively. Compared with placebo, MMA did not reduce the occurrence of POD (9 trails, 1452 patients, RR 0.93, 95% CI 0.70-1.24), with modest heterogeneity (I2 = 40%). Sensitivity analyses suggested that MMA also did not reduce the occurrence of POD in elderly patients (age ≥65 years) (6 trails, 810 patients, RR 0.71, 95% CI 0.38-1.32), patients given melatonin (4 trails, 806 patients, RR 0.78, 95% CI 0.43-1.41) or ramelteon (4 trails, 345 patients, RR 0.89, 95% CI 0.44-1.78), and patients undergoing general anesthesia (4 trails, 681 patient, RR 1.02, 95% CI 0.82-1.28). Based on the current evidence, perioperative MMA may have no effect on the prevention of POD.

Incidence, risk factors, and consequences of emergence delirium after elective brain tumor resection.

BACKGROUND: Emergence delirium (ED) is a common phenomenon occurring in the recovery period. The aim of this study was to investigate the incidence, risk factors, and consequences of ED in adults after elective brain tumor resection. METHODS: We retrospectively analyzed the data of a prospective cohort performed in a tertiary university hospital. Adult patients admitted to the intensive care unit (ICU) immediately after elective brain tumor resection were consecutively enrolled. Level of consciousness was assessed using the Richmond Agitation-Sedation Scale and ED was assessed using the Confusion Assessment Method for the ICU. Risk factors for ED were determined by multivariable logistic regression. RESULTS: A total of 659 patients met the inclusion criteria, of which 41 patients with coma were excluded. Among the remaining 618 patients, 131 (21.2%) developed ED. Independent risk factors for ED were: age, education level, use of anticholinergic and mannitol, Glasgow Coma Score and arterial partial pressure of oxygen postoperatively, postoperative pain, malignant tumor, and frontal approach craniotomy. ED was associated with increased postoperative delirium, longer length of hospital stay, and higher hospitalization costs. There was no significant difference in the neurological function deficits (modified Rankin Scale score) between ED and non-ED groups. CONCLUSIONS: ED has a high incidence and is associated with poor outcomes in adults after elective brain tumor resection. Early screening and prevention for ED should be established in perioperative management of this population.

Restrictive Versus Liberal Strategy for Red Blood-Cell Transfusion: A Systematic Review and Meta-Analysis in Orthopaedic Patients.

BACKGROUND: Current guidelines recommend restrictive criteria for red blood-cell transfusion in most clinical settings. However, patients undergoing orthopaedic surgery may require distinct transfusion criteria since benefits and potential harm often vary considerably based on patient characteristics and surgical procedures. We aimed to assess the efficacy and safety of restrictive transfusion in patients undergoing orthopaedic surgery, especially in important subgroups. METHODS: Electronic databases were searched to identify randomized controlled trials investigating restrictive (mostly a hemoglobin level of 8.0 g/dL or symptomatic anemia) versus liberal (mostly a hemoglobin level of 10.0 g/dL) transfusion in patients undergoing orthopaedic surgery. For the primary outcome of cardiovascular events, we performed random-effects meta-analyses to synthesize the evidence and to assess the effects in different subgroups according to patient characteristics (with versus without preexisting cardiovascular disease) and surgical procedures (hip fracture surgery versus elective arthroplasty). RESULTS: Ten trials involving 3,968 participants who underwent hip or knee surgery were included. Mean participant age ranged from 68.7 to 86.9 years. Compared with liberal transfusion, restrictive transfusion increased the risk of cardiovascular events (8 trials; 3,618 participants; relative risk [RR], 1.51; 95% confidence interval [CI], 1.16 to 1.98; p = 0.003; with no heterogeneity across all trials), irrespective of preexisting cardiovascular disease (pinteraction = 0.63). In a subgroup analysis, the increase was observed in patients undergoing hip fracture surgery (RR, 1.51; 95% CI, 1.08 to 2.10; p = 0.02), but did not reach significance in those undergoing elective arthroplasty (RR, 1.53; 95% CI, 0.96 to 2.44; p = 0.07). To minimize the bias caused by variations in transfusion threshold, we conducted an analysis that only included trials using 8.0 g/dL hemoglobin or symptomatic anemia as the threshold for restrictive transfusion and obtained identical results (6 trials; 2,872 participants; RR, 1.51; 95% CI, 1.09 to 2.08; p = 0.01; I = 0%). The 2 arms did not differ with respect to the rates of all infections, 30-day mortality, thromboembolic events, wound infection, pulmonary infection (mainly pneumonia), and cerebrovascular accidents (mainly stroke). CONCLUSIONS: In patients undergoing orthopaedic surgery, when compared with liberal transfusion, restrictive transfusion increases the risk of cardiovascular events irrespective of preexisting cardiovascular disease. Importantly, the increased risk was observed in patients undergoing hip fracture surgery but did not reach significance in those undergoing elective arthroplasty. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Effects of Inhalation Anesthesia vs. Total Intravenous Anesthesia (TIVA) vs. Spinal-Epidural Anesthesia on Deep Vein Thrombosis After Total Knee Arthroplasty.

BACKGROUND The objective of the present study was to evaluate the varying efficacy of general anesthesia (GA), combined spinal-epidural anesthesia (CSEA), and total intravenous anesthesia (TIVA) on the occurrence of deep vein thrombosis (DVT) following total knee arthroplasty (TKA). MATERIAL AND METHODS From July 2013 to May 2015, a total of 197 cases of patients who had undergone TKA treatment at either the Drum Tower Hospital or Nanjing General Hospital of Nanjing Military Command were recruited to participate in the study. The patients in the study were separated into 3 groups depending on the anesthesia approach received: the GA group, the CSEA group, and the TIVA group. The baseline characteristics and relative parameters of patients were monitored before and after surgery for analytic purposes. A 3-month follow-up after surgery was conducted to observe the rate of DVT occurrence and any DVT-related complications. RESULTS The TIVA group exhibited significant decreases in relation to the swallowing time reflex, extubation, and consciousness recovery in comparison to other groups in the study. Additionally, platelet count was significantly decreased and there was drastic extension of the activated partial thromboplastin time (APTT) in the CSEA group and the TIVA group. There were clear differences in the incidence of DVT and its complications among the 3 groups. The TIVA group displayed the lowest incidences of DVT and DVT-related complication during the study. Based on logistic regression analysis, the type of anesthesia was utilized as an independent correlative factor for the occurrence of DVT after surgery. CONCLUSIONS The results obtained during the study established a clinical basis for comparative analysis of various anesthesia methods. We found that, compared with GA and CSEA, patients undergoing TIVA had a reduced rate of risk in relation to the occurrence of DVT following TKA.