A Systematic Review and Evaluation of Non-Pharmacological Interventions for Elderly Patients with Mild Cognitive Impairment.

Objective: This study aims to comprehensively summarize and evaluate the impact of non-pharmacological interventions on mild cognitive impairment (MCI) in elderly individuals through a systematic review of pertinent literature. The interventions include acupuncture, massage, ear point pressing, acupoint moxibustion, dietary modifications, and exercise interventions. Methods: A thorough literature search spanned 2017 to 2023 across databases like Zhichou, Wanfang, PubMed, CINAHL, Web of Science, and the Cochrane Library. It covered pharmacological and non-pharmacological interventions, emphasising MCI in elderly patients. Independent screening, evaluation, and data extraction were conducted and assessed via the AMSTAR 2 scale and GRADE approach. Outcome measures (e.g., MMSE, MoCA, ADL, CDT, overall efficacy) were analyzed. Results: Three systematic evaluations were assessed using AMSTAR 2. Two were low quality, one moderate. Limited rigor in two studies led to considering only medium-quality papers for evidence grading. Key indicators in RCTs included MMSE (eight studies), MoCA (seven studies), ADL (two studies), CDT (two studies), and overall efficacy (12 studies). GRADE evaluation revealed moderate, high, and high evidence quality for intervention efficacy at one, two, and three months respectively. MMSE evidence was low, MoCA high, ADL very low, and CDT moderate. Adverse events were reported in one publication, suggesting acupuncture's potential pain and resistance. Conclusions: Non-pharmacological interventions, like acupuncture, cognitive exercises, and exercise, show promise in mild cognitive impairment among the elderly. They enhance cognitive function and daily living while maintaining safety. Acupuncture notably improves MoCA scores, supported by robust evidence.

Brca1 Is Upregulated by 5-Aza-CdR and Promotes DNA Repair and Cell Survival, and Inhibits Neurite Outgrowth in Rat Retinal Neurons.

Previous studies have reported that Brca1 acts as a “hinge” in the development of the central nervous system (CNS). However, the precise role of Brca1 in rat retinal neurons remains unclear. Here, we found that Brca1 is developmentally downregulated and silenced in adult retina. Brca1 was upregulated in rat primary retinal neurons by 5-Aza-2′-deoxycytidine (5-Aza-CdR) treatment. Moreover, the upregulation of Brca1 by both 5-Aza-CdR and transgenic Brca1 promoted genomic stability and improved cell viability following exposure to ionizing radiation (IR). Furthermore, transgenic Brca1 significantly inhibited neurite outgrowth of retinal neurons, which implicates that Brca1 silencing promotes cell differentiation and determines neuronal morphology. Taken together, our results reveal a biological function of Brca1 in retinal development.

Discordant mRNA and protein expression of CXCR4 under in vitro CoCl2-induced hypoxic conditions.

Cobalt chloride (CoCl2) has long been accepted as a suitable in vitro hypoxia-mimetic agent. The gene CXCR4, which encodes a chemokine receptor, plays a key role in hypoxic retinal disease. Here, we investigated the mRNA and protein expression of CXCR4 in WERI-Rb1 retinoblastoma cells and human umbilical vein endothelial cells (HUVECs) under CoCl2-induced hypoxic conditions, by means of real-time PCR and western blot. We found that CoCl2-induced hypoxia profoundly increased CXCR4 expression at the mRNA level, but not at the protein level, at 12, 24, 48 and 72 h in these cells. Interestingly, this result differed from observations of 1% O2 hypoxic conditions. Additionally, luciferase assays demonstrated that CoCl2-induced hypoxia significantly increased transcription at the CXCR4 promoter. In order to compare our in vitro findings with the effects of hypoxia in vivo, an OIR (Oxygen-induced retinopathy) rat model was constructed. However, both CXCR4 mRNA and protein levels in OIR rats were significantly increased compared to controls. Thus taken together, our findings suggest that the relationship between CXCR4 mRNA and protein expression is not strictly linear under in vitro CoCl2-induced hypoxic conditions. through comparative in vitro and in vivo experiments, this study implies that CoCl2 is an imperfect simulation of hypoxia in retinal disease.

Evaluations of aqueous humor protein markers in different types of glaucoma.

To compare the concentrations of protein markers in aqueous humor (AH) of patients with primary open-angle glaucoma (POAG), chronic angle-closure glaucoma (CACG), acute primary angle closure (APAC), and cataract without glaucoma as the control group. AH samples were collected at the beginning of surgery from 82 eyes of 82 patients who were divided into POAG (n = 23), CACG (n = 21), APAC (n = 19), and cataract groups (n = 19). The expression levels of interferon-gamma (IFN-γ), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-17A (IL-17A), lymphotoxin-alpha (LT-α), monocyte chemotactic protein-1 (MCP-1), matrix metalloproteinase-2 (MMP-2), brain derived neurotrophic factor (BDNF), basic fibroblast growth factor (bFGF), platelet-derived growth factor-AA (PDGF-AA), vascular endothelial growth factor (VEGF), tissue inhibitor of metalloproteinases-1 (TIMP-1), and tumor necrosis factor-alpha (TNF-α) in AH were detected using a microsphere-based immunoassay. The AH levels of TNF-α, MMP-2, MCP-1, IFN-γ, and TIMP-1 in the APAC and CACG groups were significantly higher than those in control eyes. Additionally, the AH levels of interleukin-6 (IL-6) and VEGF in the APAC group were significantly higher than those in the control group (CG). The interleukin-8 (IL-8) levels in patients with POAG were significantly higher than those in control eyes, whereas the LT-α levels were significantly lower than those in control eyes. IL-6 levels were significantly correlated with the coefficient of variation (CV), whereas IL-6 levels were significantly negatively correlated with the frequency of hexagonal cells (HEX) and corneal endothelial cell density (CD). The levels of TNF-α, MMP-2, MCP-1, IFN-γ, TIMP-1, IL-6, IL-8, VEGF, and LT-α were different among the three types of glaucoma. These different types of glaucoma may be caused by various pathogeneses, which opens avenues for further investigation into the pathogenesis of glaucoma and discoveries new targets and pathways for the treatment of glaucoma.

Development and validation of a clinical model (DREAM-LDL) for post-stroke cognitive impairment at 6 months.

INTRODUCTION: This multicenter, retrospective study assessed the prevalence of post-stroke cognitive impairment (PSCI) 6 months after acute ischemic stroke (AIS) and its risk factors to build a bedside early predictive model for PSCI using the Montreal Cognitive Assessment (MoCA). METHODS: Records of consecutive patients with AIS treated at 4 stroke centers in Shanghai had MoCA assessments within 2 weeks after AIS onset and 6 months later were reviewed. Prevalence of PSCI (MoCA<22) was calculated and risk factors were identified by multivariate logistic regression analysis. The modeling and validation and identified risk factors were included in a predictive model using multivariate regression. RESULTS: There were 383 patients included and prevalence of PSCI 6 months after AIS was 34.2%, significantly lower than prevalence of patients with acute cognitive impairment (49.6%). Aging, less education, higher glucose level and severe stroke were PSCI risk factors, while level of low-density lipoprotein cholesterol (LDL-C) had a paradox effect on the risk of PSCI. 40.0% of the patients with cognitive impairment at acute phase reverted to normal, and patients with LDL-C 1.8-2.5 mmol/L were more likely to revert. The predictive model we built, DREAM-LDL (Diabetes [fasting blood glucose level], Rating [NIHSS], level of Education, Age, baseline MoCA and LDL-C level), had an AUROC of 0.93 for predicting PSCI at 6 months. CONCLUSION: PSCI was common among AIS patients 6 months after AIS. We provided a practical tool to predict PSCI based on MoCA and risk factors present during acute phase of AIS.

Tetramethylpyrazine (TMP) ameliorates corneal neovascularization via regulating cell infiltration into cornea after alkali burn.

In the present study, we investigated the underlying mechanism of tetramethylpyrazine (TMP)-medicated inhibition of corneal neovascularization (CNV). Our data showed that TMP could effectively downregulate the expression levels of CXCR4 mRNA and protein, as well as inhibit HUVECs, endothelial cells, tubule formation in vitro. In vivo, alkali burn (1 M NaOH) could remarkably upregulate CXCR4 expression and increase the migration of TNF-α-positive cells to corneal stroma. TMP drops could significantly downregulate CXCR4 expression in cornea, compared to the control. However, there was no difference in the downregulation of CXCR4 between TMP and FK506, an immunosuppressive drug. Moreover, the immunofluorescent staining of CD45 showed TMP and FK506 could significantly restrain the bone marrow (BM)-derived infiltration while the F4/80 staining reflects the suppression of macrophage aggregation. Meanwhile TMP could regulate the Interleukin 10 (IL-10) and FK506 could restrain the Interleukin 2 (IL-2). Furthermore, TMP and FK506 significantly ameliorate corneal opacity and neovascularization. Clinical assessment detected an obvious improvement in TMP and FK506 treatment groups, compared to controls in vivo. Thus, TMP had similar effects in inhibition of immune response and CNV by suppressing BM-infiltrating cells into cornea as FK506. TMP could be a potential agent in eye-drop therapy for cornea damaged by Alkali Burn.

Bonding Strength of Orthodontic Brackets on Porcelain Surfaces Etched by Er:YAG Laser.

OBJECTIVE: To evaluate the effect of erbium: yttrium aluminium garnet laser conditioning bond strength of orthodontic brackets on porcelain surfaces. BACKGROUND: There are few studies that evaluate the effect of Er:YAG laser about orthodontic bonding on porcelain surface. The efficacy of Er:YAG laser in porcelain conditioning is controversial. MATERIALS AND METHODS: Ninety ceramic specimens were randomly divided into five group, group A: etched with hydrofluoric (HF) acid; group B and C: etched with an energy parameter of 250 mJ, 20 Hz and 300 mJ, 20 Hz by Er:YAG laser instrument; group D and E: etched with an energy parameter of 250 mJ, 20 Hz and 300 mJ, 20 Hz of Er:YAG laser with HF etching. Afterward, two samples selected randomly from each group were evaluated by scanning electron microscopy. Brackets were bonded on the remaining samples, which were stored in distilled water and thermocycled. Each group was measured by shear bond strength (SBS), tensile bond strength (TBS), porcelain fracture index (PFI), and adhesive remnant index (ARI) calculation. Data were statistically analyzed using SPSS software. RESULTS: The SBS and TBS in group E were the largest. Comparing SBS and TBS of HF group and other Er:YAG laser group, there were statistically significant difference (p < 0.05). PFI was significantly higher in shear force group than the tensile force group. HF group had higher ARI score than the other groups. CONCLUSIONS: Porcelain surfaces etched by 250 mJ, 20 Hz of Er:YAG laser combined with HF acid can get enough bond strength and have lower porcelain fracture rate for orthodontic bracket bonding.

Tetramethylpyrazine in a Murine Alkali-Burn Model Blocks NFκB/NRF-1/CXCR4-Signaling-Induced Corneal Neovascularization.

Purpose: Tetramethylpyrazine (TMP) is the active ingredient extracted from the Chinese herb Chuanxiong. The purpose of our study was to identify the mechanism of therapeutic TMP suppression of pathologic chemokine receptor 4 (CXCR4) transcription. Methods: C57BL/6J mice with alkali-burned corneas were treated with either TMP eye drops (1.5 mg/mL) or PBS. Corneal neovascularization (CNV) was measured and a clinical assessment was made by slit lamp microscopy. Expression of CXCR4 and the transcription factors nuclear respiratory factor-1 (NRF-1), nuclear factor kappa B (NFκB), forkhead box C1, and yin yang 1 were tracked by real-time RT-PCR and immunofluorescence staining of murine corneas. Western blot, real-time PCR, and immunofluorescence evaluated expression of related genes in human umbilical vein endothelial cells (HUVECs) after 200-µmol/L TMP treatment. In addition, plasmid transfection and chromatin immunoprecipitation assays elucidated the relationship among NRF-1, NFκB, and CXCR4. Results: Corneas treated with TMP had smaller areas of neovascularization and scored better in clinical assessments. Injured corneas showed significantly elevated expressions of NRF-1, NFκB, and CXCR4 that were normalized in vivo by TMP treatment. Similarly, in HUVECs in vitro, TMP decreased expression of NRF-1, NFκB, and CXCR4. Overexpression of NFκB or NRF-1 raised the expression of CXCR4 in HUVECs, but not synergistically. Chromatin immunoprecipitation assays detected only NRF-1 bound to the CXCR4 promoter region, suggesting NFκB controls CXCR4 expression by upregulating NRF-1. Together, our data suggest TMP downregulates CXCR4 by repressing NRF-1 expression in CNV, likely indirectly by downregulating NFκB. Conclusions: Our results implicate a novel mechanism wherein TMP inhibits neovascularization via an NFκB/NRF-1/CXCR4 circuit.

New standardized nursing cooperation workflow to reduce stroke thrombolysis delays in patients with acute ischemic stroke.

OBJECTIVE: We assessed the effectiveness of a new standardized nursing cooperation workflow in patients with acute ischemic stroke (AIS) to reduce stroke thrombolysis delays. PATIENTS AND METHODS: AIS patients receiving conventional thrombolysis treatment from March to September 2015 were included in the control group, referred to as T0. The intervention group, referred to as T1 group, consisted of AIS patients receiving a new standardized nursing cooperation workflow for intravenous thrombolysis (IVT) at the emergency department of Shanghai East Hospital (Shanghai, People's Republic of China) from October 2015 to March 2016. Information was collected on the following therapeutic techniques used: application or not of thrombolysis, computed tomography (CT) time, and door-to-needle (DTN) time. A nursing coordinator who helped patients fulfill the medical examinations and diagnosis was appointed to T1 group. In addition, a nurse was sent immediately from the stroke unit to the emergency department to aid the thrombolysis treatment. RESULTS: The average value of the door-to-CT initiation time was 38.67±5.21 min in the T0 group, whereas it was 14.39±4.35 min in the T1 group; the average values of CT completion-to-needle time were 55.06±4.82 and 30.26±3.66 min; the average values of DTN time were 100.43±6.05 and 55.68±3.62 min, respectively; thrombolysis time was improved from 12.8% (88/689) in the T0 group to 32.5% (231/712) in the T1 group (all P<0.01). In addition, the new standardized nursing cooperation workflow decreased the National Institutes of Health Stroke Scale (NIHSS) scores at 24 h (P<0.01) (T0: prethrombolysis, 6.97±3.98; 24 h postthrombolysis, 3.33±2.09; 2 weeks postthrombolysis, 2.25±1.01 and T1: prethrombolysis, 7.00±3.89; 24 h postthrombolysis, 2.60±1.66; 2 weeks postthrombolysis, 2.21±1.02). CONCLUSION: The new standardized nursing cooperation workflow reduced stroke thrombolysis delays in patients with AIS.