The cognitive effect of non-invasive brain stimulation combined with cognitive training in Alzheimer's disease and mild cognitive impairment: a systematic review and meta-analysis.

BACKGROUND: Non-invasive brain stimulation (NIBS) combined with cognitive training (CT) may have shown some prospects on improving cognitive function in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). However, data from clinical trials or meta-analysis involving NIBS combined with CT have shown controversial results. The aim of this systematic review and meta-analysis was to evaluate short-term and long-term effects of NIBS combined with CT on improving global cognition and other specific cognitive domains in patients with AD and MCI. METHODS: This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Five electronic databases including PubMed, Web of Science, EBSCO, Cochrane Library and Embase were searched up from inception to 20 November 2023. The PEDro scale and the Cochrane's risk of bias assessment were used to evaluate risk of bias and methodological quality of included studies. All statistical analyses were conducted with Review Manager 5.3. RESULTS: We included 15 studies with 685 patients. The PEDro scale was used to assess methodological quality with a mean score of 7.9. The results of meta-analysis showed that NIBS combined with CT was effective on improving global cognition in AD and MCI (SMD = 0.52, 95% CI (0.18, 0.87), p = 0.003), especially for patients accepting repetitive transcranial magnetic stimulation (rTMS) combined with CT (SMD = 0.46, 95% CI (0.14, 0.78), p = 0.005). AD could achieve global cognition improvement from NIBS combined with CT group (SMD = 0.77, 95% CI (0.19, 1.35), p = 0.01). Transcranial direct current stimulation (tDCS) combined with CT could improve language function in AD and MCI (SMD = 0.29, 95% CI (0.03, 0.55), p = 0.03). At evaluation follow-up, rTMS combined with CT exhibited larger therapeutic responses to AD and MCI in global cognition (SMD = 0.55, 95% CI (0.09, 1.02), p = 0.02). AD could achieve global cognition (SMD = 0.40, 95% CI (0.03, 0.77), p = 0.03) and attention/working memory (SMD = 0.72, 95% CI (0.23, 1.20), p = 0.004) improvement after evaluation follow-up from NIBS combined with CT group. CONCLUSIONS: Overall, NIBS combined with CT, particularly rTMS combined with CT, has both short-term and follow-up effects on improving global cognition, mainly in patients with AD. tDCS combined with CT has advantages on improving language function in AD and MCI. Future more studies need evaluate cognitive effects of NIBS combined with CT on other specific cognitive domain in patients with cognitive deterioration.

The Influence of Exercise on Cancer Risk, the Tumor Microenvironment and the Treatment of Cancer.

There are several modifiable factors that can be targeted to prevent and manage the occurrence and progression of cancer, and maintaining adequate exercise is a crucial one. Regular physical exercise has been shown to be a beneficial strategy in preventing cancer, potentially amplifying the effectiveness of established cancer therapies, alleviating certain cancer-related symptoms, and possibly mitigating side effects resulting from treatment. Nevertheless, the exact mechanisms by which exercise affects tumors, especially its impact on the tumor microenvironment (TME), remain uncertain. This review aims to present an overview of the beneficial effects of exercise in the context of cancer management, followed by a summary of the exercise parameters, especially exercise intensity, that need to be considered when prescribing exercise for cancer patients. Finally, we discuss the influence of exercise on the TME, including its effects on crucial immune cells (e.g., T cells, macrophages, neutrophils, natural killer cells, myeloid-derived suppressor cells, B cells), intratumor angiogenesis, and cancer metabolism. This comprehensive review provides up-to-date scientific evidence on the effects of exercise training on cancer and offers guidance to clinicians for the development of safe and feasible exercise training programs for cancer patients in clinical practice.

Pimavanserin tartrate induces apoptosis and cytoprotective autophagy and synergizes with chemotherapy on triple negative breast cancer.

Triple negative breast cancer (TNBC) poses a significant clinical challenge due to its lack of targeted therapy options and the frequent development of chemotherapy resistance. Metastasis remains a primary cause of mortality in late-stage TNBC patients, underscoring the urgent need for alternative treatments. Repurposing existing drugs offers a promising strategy for the discovery of novel therapies. In this study, we investigated the potential of pimavanserin tartrate (PVT) as a treatment for TNBC. While previous studies have highlighted PVT's anticancer effects in various cancer types, its activity in TNBC remains unclear. Our investigation aimed to elucidate the anticancer effects and underlying mechanisms of PVT in TNBC. We evaluated the impact of PVT and combination treatments involving PVT on TNBC cell viability, apoptosis, autophagy, and associated signaling pathways. Our findings revealed that PVT may induce mitochondria-dependent intrinsic apoptosis and caused cytoprotective autophagy via the PI3K/Akt/mTOR pathway in TNBC cells in vitro. Notably, our study demonstrated strong synergistic anti-TNBC effects when combining PVT with doxorubicin. We also found PVT showed some efficacies to inhibit TNBC tumor growth in vivo. These results provided valuable insights into the potential of PVT as an anti-TNBC therapeutic and a possible option for enhancing the sensitivity of TNBC cells to conventional chemotherapy drugs. Further studies are needed to determine the activity and mechanism of PVT in inhibiting TNBC.

Effect of transcranial direct current stimulation for patients with disorders of consciousness: A systematic review and meta-analysis.

Introduction: Transcranial direct current stimulation (tDCS) could potentially facilitate consciousness improvement in patients with disorders of consciousness (DOC). The aim of this study was to investigate the therapeutic efficacy of tDCS on consciousness recovery for patients with DOC. Methods: Eight databases were systematically searched from their inception to June 2022. Quality of included studies were assessed using PEDro score and Cochrane's risk of bias assessment. All statistical analyses were performed using RevMan software. Seventeen studies with 618 patients were identified eligible for this study, and fifteen studies with sufficient data were pooled in the meta-analysis. Results: The results of meta-analysis showed a significant effect on increasing GCS scores (MD = 1.73; 95% CI, 1.28-2.18; P < 0.01) and CRS-R scores (MD = 1.28; 95% CI = 0.56-2.00; P < 0.01) in favor of the real stimulation group as compared to sham. The results of subgroup analysis demonstrated that only more than 20 sessions of stimulation could significantly enhance the improvement of GCS scores and the CRS-R scores. Moreover, the effect of tDCS on CRS-R score improvement was predominant in patients with minimal conscious state (MCS) (MD = 1.84; 95% CI = 0.74-2.93; P < 0.01). Conclusion: Anodal tDCS with sufficient stimulation doses appears to be an effective approach for patients with MCS, in terms of CRS-R scores. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022336958.

Effectiveness of Elastic Taping in Patients With Knee Osteoarthritis: A Systematic Review and Meta-Analysis.

OBJECTIVE: The aim of the study was to assess the effects of elastic taping on pain, physical function, range of motion, and muscle strength in patients with knee osteoarthritis. DESIGN: We searched the PubMed, the Cochrane Central Register of Controlled Trials, Web of Science, Physiotherapy Evidence Database, Scopus, EMBASE, OVID, CNKI, and WANFANG to identify relevant randomized controlled trials. The primary outcome measures were pain and physical function. The secondary outcome measures were range of motion and muscle strength. RESULTS: Eleven randomized controlled trials involving 490 patients with knee osteoarthritis were included. A statistically significant difference was detected in pain (standardized mean difference = -0.78, 95% confidence interval = 1.07 to -0.50, P < 0.00001), physical function (standardized mean difference = 0.73, 95% confidence interval = -1.03 to -0.43, P < 0.00001), range of motion (mean difference = 2.04, 95% confidence interval = 0.14 to 3.94, P = 0.04), and quadriceps muscle strength (mean difference = 2.42, 95% confidence interval = 1.09 to 3.74, P = 0.0004). No significant differences were found for the hamstring muscle strength. CONCLUSIONS: Elastic taping has significant effects on pain, physical function, range of motion, and quadriceps muscle strength in patients with knee osteoarthritis. The current evidence is insufficient to draw conclusions on the effects of elastic taping combined with other physiotherapy for knee osteoarthritis. Further studies are needed to investigate the long-term effects of elastic taping combined with other physiotherapy compared with elastic taping alone for knee osteoarthritis.

Antipsychotic Drug Trifluoperazine Suppresses Colorectal Cancer by Inducing G0/G1 Arrest and Apoptosis.

Repurposing existing drugs for cancer treatment is an effective strategy. An approved antipsychotic drug, trifluoperazine (TFP), has been reported to have potential anticancer effects against several cancer types. Here, we investigated the effect and molecular mechanism of TFP in colorectal cancer (CRC). In vitro studies showed that TFP induced G0/G1 cell cycle arrest to dramatically inhibit CRC cell proliferation through downregulating cyclin-dependent kinase (CDK) 2, CDK4, cyclin D1, and cyclin E and upregulating p27. TFP also induced apoptosis, decreased mitochondrial membrane potential, and increased reactive oxygen species levels in CRC cells, indicating that TFP induced mitochondria-mediated intrinsic apoptosis. Importantly, TFP significantly suppressed tumor growth in two CRC subcutaneous tumor models without side effects. Interestingly, TFP treatment increased the expression levels of programmed death-1 ligand 1 (PD-L1) in CRC cells and programmed death-1 (PD-1) in tumor-infiltrating CD4+ and CD8+ T cells, implying that the combination of TFP with an immune checkpoint inhibitor, such as an anti-PD-L1 or anti-PD-1 antibody, might have synergistic anticancer effects. Taken together, our study signifies that TFP is a novel treatment strategy for CRC and indicates the potential for using the combination treatment of TFP and immune checkpoint blockade to increase antitumor efficiency.

Autophagy: A Promising Target for Age-related Osteoporosis.

Autophagy is a process the primary role of which is to clear up damaged cellular components such as long-lived proteins and organelles, thus participating in the conservation of different cells. Osteoporosis associated with aging is characterized by consistent changes in bone metabolism with suppression of bone formation as well as increased bone resorption. In advanced age, not only bone mass but also bone strength decrease in both sexes, resulting in an increased incidence of fractures. Clinical and animal experiments reveal that age-related bone loss is associated with many factors such as accumulation of autophagy, increased levels of reactive oxygen species, sex hormone deficiency, and high levels of endogenous glucocorticoids. Available basic and clinical studies indicate that age-associated factors can regulate autophagy. Those factors play important roles in bone remodeling and contribute to decreased bone mass and bone strength with aging. In this review, we summarize the mechanisms involved in bone metabolism related to aging and autophagy, supplying a theory for therapeutic targets to rescue bone mass and bone strength in older people.

Effects of Tai Chi on balance and fall prevention in Parkinson's disease: a randomized controlled trial.

OBJECTIVES: To examine the effects of Tai Chi on balance and functional mobility in people with Parkinson's disease, and determine whether fall incidence could be reduced by the Tai Chi exercise. DESIGN: Single blinded randomized control trial with 6 months' follow-up. SETTING: A hospital and general community. PARTICIPANTS: Patients (n=76) diagnosed with idiopathic Parkinson's disease, over 40 years old, able to walk independently and fell at least one time during the past 12 months. INTERVENTIONS: The Tai Chi group (n=37) received 24-form Yang style Tai Chi exercise for 60 minutes each time, three times a week and lasted for 12 weeks. The control group (n=39) received no intervention. MAIN OUTCOME MEASURES: Berg Balance Scale (BBS), Unified Parkinson's Disease Rating Scale (UPDRS) III, Timed Up&Go (TUG) and occurrences of falls. RESULTS: The Tai Chi group improved more than the control group on the BBS (p<0.05), but there was no difference on UPDRS III scores and Timed Up&Go (p>0.05). During the 6-month follow-up, only 8 (21.6%) out of 37 patients in the Tai Chi group had experience of falls comparing to 19 (48.7%) out of 39 patients in the control group (p<0.05). The average times of falls were 0.30±0.62 in the Tai Chi group compared with 0.64±0.74 in the control group (p<0.05). CONCLUSIONS: Our findings suggested that Tai Chi exercise could improve the balance and decrease the fall risks in patients with Parkinson's disease.