The metabolic score for insulin resistance as a predictor of clinical outcome in stroke patients treated by intravenous thrombolysis.

BACKGROUND AND PURPOSE: Insulin resistance is associated with clinical outcomes among patients with ischemic stroke. We aimed to investigate the association between metabolic score for insulin resistance (METS-IR) and clinical outcomes in stroke patients treated by intravenous thrombolysis (IVT). METHODS: We recruited participants treated with IVT from a prospective registry including 3 stroke centers. Poor outcome was defined as a modified Rankin scale score ≥ 3 points at 90 days after the index stroke. We performed logistic regression models to investigate the association between METS-IR and the risk of poor outcome. We used the receiver operative characteristic to assess the discriminative ability and the restricted cubic spline to explore the relationship between METS-IR and the poor outcome. RESULTS: This study enrolled a total of 1074 patients (median age, 68; 63.8% male). Three hundred sixty (33.5%) patients had poor outcome after IVT. METS-IR was associated with the risk of the poor outcome with the increase of confounding factors in models (odds ratio [OR], 1.078; 95% confidence interval [CI], 1.058-1.099; P < 0.001). The area under the curve for METS-IR for predicting the poor outcome was 0.790 (95% CI, 0.761-0.819). The restricted cubic spline revealed an increasing and non-linear association between METS-IR and the poor outcome (P for non-linearity < 0.001). CONCLUSION: Our study found that METS-IR was associated with an increased risk of poor outcome after IVT. Further studies are warranted to investigate the efficacy of anti-diabetic agents regarding IR on clinical outcomes after IVT.

Effect of fasting on cancer: A narrative review of scientific evidence.

Emerging evidence suggests that fasting could play a key role in cancer treatment by fostering conditions that limit cancer cells' adaptability, survival, and growth. Fasting could increase the effectiveness of cancer treatments and limit adverse events. Yet, we lack an integrated mechanistic model for how these two complicated systems interact, limiting our ability to understand, prevent, and treat cancer using fasting. Here, we review recent findings at the interface of oncology and fasting metabolism, with an emphasis on human clinical studies of intermittent fasting. We recommend combining prolonged periodic fasting with a standard conventional therapeutic approach to promote cancer-free survival, treatment efficacy and reduce side effects in cancer patients.

KLF4 alleviates cerebral vascular injury by ameliorating vascular endothelial inflammation and regulating tight junction protein expression following ischemic stroke.

BACKGROUND: Although inflammatory cell adhesion molecules (CAMs) and anti-inflammation factor Kruppel-like transcription factor (KLF) 4 have all been reported to be induced after cerebral ischemic stroke (CIS), the close temporal and spatial relationship between expressions of CAMs and KLF4 following CIS and whether and how CAMs and KLF-4 contribute to the development of CIS-induced vascular injury are still unclear. METHODS: Here, we first examined the correlation between serum levels of CAMs/KLF4 and infarct volume in acute CIS patients. Then, we determined the relationship between CAMs and KLF4 in mice after focal cerebral ischemia. Finally, we investigated the mechanism of KLF4 in protecting against oxygen-glucose deprivation-induced brain endothelial cell injury. RESULTS: Our results demonstrated that patients with moderate to severe CIS had higher serum levels of three CAMs including E-selectin, inter-cellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1) but lower levels of KLF4 at 48 h after an acute event as compared to patients with minor CIS. The expression levels of three CAMs as well as KLF4 all correlated well with the infarct volume in all the CIS subjects at that time. Although the expressions of three CAMs and KLF4 were all induced in the ischemic hemisphere following focal cerebral ischemia, the peak timing and distribution patterns of their expression were different: the induction of KLF4 lagged behind that of the CAMs in the ischemic penumbra; furthermore, the dual immunofluorescent studies displayed that high expression of KLF4 was always associated with relatively less cerebral vascular endothelial inflammation response in the ischemic hemisphere and vice versa. Mechanistic analyses revealed that KLF4 alleviated CIS-induced cerebral vascular injury by regulating endothelial expressions of CAMs, nuclear factor-kB, and tight junction proteins. CONCLUSIONS: These data indicate that KLF4 confers vascular protection against cerebral ischemic injury, suggesting that circulating CAMs and KLF4 might be used as potential biomarkers for predicting the prognosis of acute ischemic stroke and also providing a new proof of concept and potential targets for future prevention and treatment of CIS.

Differential Association of Serum BDNF With Poststroke Depression and Poststroke Anxiety.

OBJECTIVES: To investigate the correlation between brain-derived neurotrophic factor (BDNF) and risk factors, as well as functional outcome in poststroke depression (PSD) or poststroke anxiety (PSA). DESIGN: Cohort study. SETTING: Stroke patients admitted to an urban rehabilitation hospital. PARTICIPANTS: Stroke patients (N=162) without any previous history of depression and anxiety. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Sociodemographic information and comorbidities were recorded during hospital admission. Functional outcomes were assessed using FIM scores at time of admission and discharge. The influence of various factors such as BDNF and patient characteristics on functional outcome was investigated. Single-factor effect was examined using simple logistic regression, as was multi-factor effect using multiple logistic regression. The goodness-of-fit of those regression models was evaluated by the integrated area under ROC curve. RESULTS: PSD was diagnosed in 61 (37.7%) patients, and PSA was diagnosed in 40 (24.7%). Multiple logistic analysis showed that BDNF, divorce or separation, and history of smoking were significantly associated with the occurrence of PSD but not with the occurrence of PSA. The model combining low BDNF level and divorce or separation improved the prediction for PSD. Among the variables analyzed for prediction of functional outcome, serum BDNF had a minimum correlation with motor FIM scores in PSD but no significant correlation with motor FIM scores in PSA. CONCLUSIONS: BDNF is a valuable prediction for the occurrence of PSD but not for PSA. More strikingly, ischemic stroke patients who are divorced or separated with low serum BDNF have a much higher risk for PSD. BDNF has a minimum correlation with motor function outcome in PSD but no significant correlation with motor outcome in PSA.

Immunotherapy: Advancing glioblastoma treatment-A narrative review of scientific studies.

BACKGROUND: Glioblastoma (GB) is an aggressive and deadly brain tumor with a poor prognosis despite the current standard of care, including surgery, radiation, and chemotherapy. RECENT FINDINGS: In recent years, there has been increasing interest in the potential of immunotherapies, seen to be effective in treating other cancers, in the treatment of GB. This comprehensive review presents an in-depth analysis of the remarkable progress of immunotherapy in GB treatment, focusing on human clinical studies. It also analyzes the current findings, challenges, and limitations that underscore the transformative potential of immunotherapy in managing GB. Of particular significance, it delves into the intriguing interaction of the human microbiome with immunotherapy as a novel avenue for enhancing treatment outcomes of GB. CONCLUSION: This study sheds light on the complex GB therapy landscape and the cutting-edge strategies that show promise for enhancing patient prognosis.

Association of peripheral manifestation of brain-derived neurotrophic factor with depression: A meta-analysis.

BACKGROUND: The relationship between brain-derived neurotrophic factor (BDNF) and depression is a hot topic in research as several results of preclinical and clinical studies have shown controversial results. Our meta-analysis aims to evaluate and update the current status of peripheral BDNF with depression. METHODS: We performed a meta-analysis by comprehensively searching PubMed and Web of Science for English-language literature from inception to 1st of June 2020. The search terms included brain-derived neurotrophic factor or BDNF in combination with depression, without year restriction. Using STATA software, data were pooled using a random-effects model. RESULTS: In our literature search, 24 studies involving 1130 depressed patients and 1378 healthy individuals met our inclusion criteria. The results of our meta-analysis showed that the peripheral levels of BDNF levels significantly decreased in depression than nondepressed healthy controls (SMD = -0.89, 95% CI = -1.41, -0.38, p < .0001); however, the significant heterogeneity among studies (Q = 740.91, I2  = 96.8; p < .001) was discovered. Trim-and-fill estimations for the adjustment of publication bias indicated that publication bias had no impact on our results. Our sub-group analysis showed that a history of depression and alcohol consumption had an effect on the level of BDNF. In addition, age and gender did not affect the heterogeneity of BDNF in the meta-analysis. CONCLUSIONS: Although decreased peripheral expression of BDNF certainly presents a risk of depression, we cannot find a definite relationship between the peripheral level of BDNF with depression to use BDNF as a reliable biomarker to assess the depression in clinical practice. We propose that future research should consider all the factors affecting BDNF and assess the level of proBDNF and mBDNF separately while evaluating the patients with depression objectively.

Chinese Medicine, Succinum, Ameliorates Cognitive Impairment of Carotid Artery Ligation Rats and Inhibits Apoptosis of HT22 Hippocampal Cells via Regulation of the GSK3ß/ß-Catenin Pathway.

Succinum is an organic mineral formed from the resin of ancient coniferous and leguminous plants, which is applied for tranquilizing mood, promoting blood circulation, and removing blood stasis in Chinese medicine. For quite a long time, the modern research of succinum mainly focuses on the study of physical and chemical properties and authenticity identification while few reports on its medicinal mechanism. In current study, we evaluated different solvent extracts of succinum on carotid artery ligation rats mimicking vascular dementia. It was found that ethyl acetate extracts of succinum significantly improved the learning and memory abilities of model rats and inhibited neuronal apoptosis in the hippocampus. On a mice hippocampal neuronal cell line (HT22), ethyl acetate extracts of succinum also exerted better action trend in inhibiting cell apoptosis induced by oxygen glucose deprivation (OGD). By using XAV-939 on both in vivo and in vitro studies, it was found that ethyl acetate extracts of succinum might exert these functions by regulating the GSK3ß/ß-catenin pathway. These studies revealed the neuronal function of succinum, which explained the traditional effects of succinum and provided more modern scientific basis for its clinical application.

BDNF Met allele Is Associated With Lower Cognitive Function in Poststroke Rehabilitation.

Background and purpose. The identification of a genetic role for cognitive outcome could influence the design of individualized treatment in poststroke rehabilitation. The aim of this study is to determine whether brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is independently associated with poststroke functional outcome. Methods. A total of 775 stroke patients with genomic data were identified from the Partners HealthCare Biobank, which contains a large number of genotypes from Biobank's consented patients. Of 775 stroke patients who met the inclusion/exclusion criteria, 86 were enrolled. Functional outcomes were assessed using the Functional Independence Measure scores at the time of admission and discharge. Logistic and linear regression models adjusted for covariate variables, including age, sex, and medical conditions, were used to evaluate the association between BDNF Val66Met and functional outcome. Results. We detected a significant correlation between Met alleles and lower cognitive function at discharge in both ischemic and hemorrhagic stroke patients. Genotyping findings confirmed that BDNF Met allele frequency was higher in contrast to Val/Val allele frequency in lower cognitive functional recovery. Furthermore, after adjusting for covariate variables, BDNF Met alleles were found to be associated with lower cognitive outcome [P = .003; odds ratio (OR) = 5.95 (1.81-19.52)] and recovery [P = .006; OR = 3.16 (1.4-7.15)], especially with lower problem solving, expression, and social recovery in all stroke patients. Conclusions. Met allele carriers exhibited impaired poststroke cognitive function. The BDNF genotype may be a useful predictor of cognitive function in inpatient poststroke rehabilitation.

Jia-Wei-Kai-Xin-San, an Herbal Medicine Formula, Ameliorates Cognitive Deficits via Modulating Metabolism of Beta Amyloid Protein and Neurotrophic Factors in Hippocampus of Aß1-42 Induced Cognitive Deficit Mice.

Jia-Wei-Kai-Xin-San (JWKXS) is a Chinese medicine formula applied for treating morbid forgetfulness in ancient China. Today, this formula is frequently applied for Alzheimer's disease and vascular dementia (VD) in clinic. Here, we developed it as granules and aimed to evaluate its anti-AD effect on ß amyloid protein 1-42 (Aß1-42) induced cognitive deficit mice and reveal the possible molecular mechanisms. Firstly, daily intra-gastric administration of chemically standardized of JWKXS granules for 7 days significantly ameliorated the cognitive deficit symptoms and inhibited cell apoptosis in hippocampus on Aß1-42 injection mice. JWKXS granules significantly decreased Aß level, increased superoxide dismutase activity and decreased malondialdehyde level in hippocampus of model mice. It also restored acetylcholine amounts, inhibited acetylcholinesterase activities and increased choline acetyltransferase activities. In addition, JWKXS granules enabled the transformation of precursors of NGF and BDNF into mature forms. Furthermore, JWKXS granules could regulate gene expressions related to Aß production, transportation, degradation and neurotrophic factor transformation, which led to down-regulation of Aß and up-regulation of NGF and BDNF. These findings suggested that JWKXS granules ameliorated cognitive deficit via decreasing Aß levels, protecting neuron from oxidation damages and nourishing neuron, which could serve as alternative medicine for patients suffering from AD.

[Dynamic scalp acupuncture combined with PNF therapy for upper limb motor impairment in ischemic stroke spastic hemiplegia].

OBJECTIVE: On the basic therapy, to assess the clinical effects of dynamic scalp acupuncture, scalp acupuncture combined with proprioceptive neuromuscular facilitation (PNF) therapy and simple PNF therapy for upper limb motor impairment in ischemic post-stroke spastic hemiplegia. METHODS: A total of 90 cases were randomly assigned into a PNF group, a dynamic scalp acupuncture group and a scalp acupuncture group, 30 cases in each group. Basic therapy and PNF therapy were applied in the three groups. PNF therapy was used during scalp acupuncture in the dynamic scalp acupuncture group. PNF therapy was applied after scalp acupuncture in the scalp acupuncture group. The points were the upper 1/5 and middle 2/5 of Dingnieqianxiexian (MS 6) and Dingniehouxiexian (MS 7) at the lesion side, the hemiparalysis contralateral side. The treatment was given for 6 months, once a day and 1 month as a course. The modified Ashworth scale (MAS), the Fugl-Meyer motor assessment (FMA) and Barthel index (BI) were observed before treatment and 2 weeks, 1 month, 3 months, and 6 months after treatment. RESULTS: The MAS 1 month, 3 months and 6 months after treatment were improved compared with those before treatment in the three groups ( all P<0.05), and the MAS results in the dynamic scalp acupuncture group were better than those in the PNF and scalp acupuncture group (all P<0.05). The FMA and BI scores 1 month, 3 months and 6 months after treatment were higher than those before treatment (all P<0.05). The FMA Scores in the 3 time points and after treatment in the dynamic scalp acupuncture group were higher than those in the other two groups (all P<0.05). CONCLUSION: PNF therapy during scalp acupuncture can relieve the spasmodic condition of patients with upper limb motor impairment in ischemic post-stroke spasmodic hemiplegia, and improve the limb function and life activity, which is better than PNF therapy after scalp acupuncture and simple PNF therapy.

An electricity price model with consideration to load and gas price effects.

Some characteristics of the electricity load and prices are studied, and the relationship between electricity prices and gas (fuel) prices is analyzed in this paper. Because electricity prices are strongly dependent on load and gas prices, the authors constructed a model for electricity prices based on the effects of these two factors; and used the Geometric Mean Reversion Brownian Motion (GMRBM) model to describe the electricity load process, and a Geometric Brownian Motion(GBM) model to describe the gas prices; deduced the price stochastic process model based on the above load model and gas price model. This paper also presents methods for parameters estimation, and proposes some methods to solve the model.

[Program optimization in the stage treatment of periarthritis of shoulder with acupuncture, moxibustion and positive functional exercise].

OBJECTIVE: To optimize the therapeutic programs for periarthritis of shoulder treated with acupuncture, moxibustion and kinetohterapy with orthogonal design method adopted. METHODS: The orthogonal design table of L8 (2(7)) hierarchical principle was used to randomly divide 192 patients of periarthritis of shoulder into 8 groups, 24 cases in each one. Separately, 4 factors and each different 2 levels were adopted in treatment, named acupuncture timing (factor A: A, acute stage, A2 adhesion stage), acupoint combination (factor B: B, local acupoints, B2 local acupoints and distal acupoints along meridians), filiform needling and warm needling therapy (factor C: C1 acupuncture with filiform needle, CZ acupuncture with filiform needle and warm needling therapy) and positive functional exercise (factor D: D1 without positive functional exercise, D2 with positive functional exercise). The treatment was given once a day, 10 treatments made one session and 2 sessions were required totally. The time points of observation were the point after 1 session of treatment and after 2 sessions of treatment. The short-form McGill pain questionnaire (MPQ) and shoulder joint motor disturbance score were adopted for evaluation. RESULTS: In the orthogonal design analysis, taking the hierarchical factors into consideration, the age was considered as the main factor in the evaluation of shoulder pain and shoulder motor disturbance (P<0.01), and the shoulder function grade apparently impacted pain evaluation and the efficacy on shoulder motor disturbance (P<0.01). The best combination of 4 factors and 2 levels were A1B1CzD2 and A2BC2D2. SAS statistical analysis showed that at acute stage and adhesion stage, CZ Dz , meaning acupuncture with fifiform needling and warm needling therapy combined with positive functional exercise, is the main factor of the improvements of shoulder motor function (P<0.05). CONCLUSION: For periarthritis of shoulder at acute stage, the combined therapy of acupuncture at local acupoints, warm needling and positive functional exercise is adopted. At chronic stage, the combined therapy of acupuncture at local acupoints and distal acupoints, acupuncture with filiform needle and warm needling and positive functional exercise is the best program. Additionally, in clinical treatment, the patients' age, sex, shoulder joint function and duration of treatment should be considered comprehensively for the impacts on the efficacy.

[Effects of heavenly stem-prescription of point selection of needling methods of Ziwu Liuzhu on ischemic cerebrovascular diseases].

OBJECTIVE: To observe effects of heavenly stem-prescription of point selection of the needling methods of midnight-noon ebb-flow on motorial and neurological functional deficit of ischemic cerebrovascular diseases. METHODS: The patients were randomly divided into a Ziwu Liuzhu group and a channel acupoint selection group. In the channel acupoint selection group, Jianyu (LI 15), Quchi (LI 11), Waiguan (TE 5), Zusanli (ST 36) were selected, combined with selected acupoints by syndrome differentiation. In the Ziwu Liuzhu group, on the basis of the channel acupoint selection group, according to the principle "the acupoints of the yang-channel were opened at yang-day-yang-hour and the acupoints of the yin-channel were opened at yin-day-yin-hour", and acupoints were selected by the day-hour acupoint-opening method of the Ziwu Liuzhu Najia method in Zhenjiu Daquan. The patients in the both groups began to be treated at the Chen hour (7:00-9:00) or Si hour (9:00-11:00) in the morning, 10 times constituting one course. They were treated for 3 courses. Improvement of the motor function symptom cumulative score, Fugl-Meyer (FMA) and improvement of neurological functional deficit were investigated. RESULTS: The FMA score (36.13 +/- 21.80) after treatment was significantly lower than (73.50 +/- 21.53) before treatment (P<0.01) in the Ziwu Liuzhu group, and (54.43 +/- 20.89) after treatment was significantly lower than (62.27 +/- 22.91) before treatment (P<0.05) in the channel acupoint selection group; the neurological functional deficit score (15.40 +/- 9.34) after treatment was significantly lower than (27.17 +/- 10.81) before treatment in the Ziwu Liuzhu group, and (23.97 +/- 1.30) was lower than (27.97 +/- 7.72) before treatment in the channel acupoint selection group. After treatment, FMA and the neurological functional scores significantly improved in the Ziwu Liuzhu group as compared with those in the channel acupoint selection group (P<0.05). CONCLUSION: Ziwu Liuzhu Najia point-selection method can effectively improve both nervous function and motor function in the patient of ischemic cerebrovascular disease.