Experience of financial toxicity and coping strategies in young and middle-aged patients with stroke: a qualitative study.

BACKGROUND: While financial toxicity (FT) is prevalent in patients with cancer, young and middle-aged patients with stroke are also affected by FT, which can exacerbate their physical and psychological challenges. Understanding the patient's experience and response measures can further understand the impact of FT on patients with stroke, to help alleviate FT. However, little is known concerning the experience of patients with stroke with FT or their coping strategies. Therefore, this study aimed to describe the experiences of FT in young and middle-aged patients with stroke and their coping strategies. METHODS: A phenomenological method was utilized. Semi-structured interviews were conducted with 21 young and middle-aged stroke patients (aged 18-59) between October 2022 and March 2023. The participants were recruited from a tertiary hospital in Shanghai, China. The research team used NVivo 12.0 software. Giorgi's phenomenological analysis method was used to analyse the interview data. RESULTS: The interview results were divided into two categories in terms of patients' experiences of FT and their coping strategies. Nine subthemes were constructed. The experience category included four subthemes: (1) taking on multifaceted economic pressure, (2) dual choice of treatment, (3) decline in material living standards, and (4) suffering from negative emotions such as anxiety and depression. The coping strategy category included five subthemes: (1) reducing expenses, (2) improving living habits, (3) proactive participation in medical decision-making, (4) making a job position choice, and (5) seeking social support. CONCLUSIONS: FT in young and middle-aged patients with stroke, which affected their physical and mental health, led them to implement strategies for dealing with FT. The Chinese government needs to broaden the reach of health insurance coverage and advance the fairness of healthcare policies. Healthcare professionals must pay active attention to FT in such patients in terms of strengthening their health education and considering their needs and preferences. Patients need to improve their sense of self-efficacy, actively reintegrate into society, and adhere to rehabilitation and treatment. Individuals at a high risk of stroke are recommended to purchase health insurance. Multifaceted efforts are needed to reduce the impact of FT in young and middle-aged patients with stroke.

MiR-29c-3p inhibits proliferation and migration in rat primary cardiac fibroblasts via interacting with STAT3.

BACKGROUND: The aim of this study was to elucidate the influence and molecular mechanism of microRNA-29c-3p (miR-29c-3p) on cell functions of cardiac fibroblasts. METHODS: Rat primary cardiac fibroblasts were induced with high-level glucose (HG), followed by determination of miR-29c-3p and signal transducer and activator of transcription 3 (STAT3) levels. The regulatory effects of miR-29c-3p and STAT3 (AG490) on proliferative and migratory potentials in HG-induced cardiac fibroblasts were examined by cell counting kit-8 (CCK-8) and Transwell assay, respectively. The interaction between miR-29c-3p and STAT3 was assessed by bioinformatics analysis and dual-luciferase reporter assay. RESULTS: MiR-29c-3p was downregulated, and STAT3 was upregulated in HG-induced cardiac fibroblasts. HG induction stimulated proliferative and migratory potentials in cardiac fibroblasts, which were attenuated by overexpression of miR-29c-3p. STAT3 was the target gene binding miR-29c-3p. Application of AG490, the STAT3 inhibitor, was able to reverse the promoted proliferative and migratory potentials in HG-induced cardiac fibroblasts with miR-29c-3p knockdown. CONCLUSIONS: MiR-29c-3p weakens the over-proliferative and over-migratory potentials in HG-induced cardiac fibroblasts via inactivating the STAT3 signaling.

Effect of early integrated robot-assisted gait training on motor and balance in patients with acute ischemic stroke: a single-blinded randomized controlled trial.

Background: Gait disruption is a common poststroke problem. Robot-assisted gait training (RAGT) might improve motor function, balance, and activities of daily living. Objective: We compared the clinical effectiveness of early integrated RAGT using the Walkbot robotic gym with an intensity-matched enhanced lower limb therapy (ELLT) program and with conventional rehabilitation therapy (CRT) in patients with acute ischemic stroke. Methods: A total of 192 patients with acute ischemic stroke were randomly assigned (1:1:1) to receive RAGT, ELLT, or CRT. All three groups received 45 min of training daily, 3 days a week, for 4 weeks consecutively. Before and after the 4-week treatment, the patients were assessed based on a 6-minute walking test (6MWT), functional ambulation classification (FAC), timed up and go (TUG) test, dual-task walking (DTW) test, Tinetti's test, Barthel's index (BI), stroke-specific quality of life (SS-QOL) scale, and gait analysis parameters. Results: After the 4-week intervention, the results of the 6MWT, FAC, TUG, DTW, Tinetti's test, BI, SS-QOL, and gait in the three groups significantly improved. Compared with ELLT and CRT groups, participants in the RAGT group had a better performance in 6MWT (199.11 ± 60.72 versus 182.47 ± 59.72 versus 173.69 ± 40.58, p = 0.035), FAC (4.10 ± 0.91 versus 3.69 ± 0.88 versus 3.58 ± 0.81, p = 0.044), DTW (10.29 ± 2.38 versus 12.92 ± 2.64 versus 13.89 ± 2.62, p = 0.031), SS-QOL (184.46 ± 20.53 versus 165.39 ± 20.49 versus 150.72 ± 20.59, p = 0.012), velocity (0.66 ± 0.22 versus 0.55 ± 0.23 versus 0.51 ± 0.20, p = 0.008), cycle duration (1.38 ± 0.40 versus 1.50 ± 0.38 versus 1.61 ± 0.30, p = 0.040), and swing phase symmetry ratio (SPSR, 1.10 ± 0.33 versus 1.21 ± 0.22 versus 1.48 ± 0.25, p = 0.021). The TUG, Tinetti's test, BI, and RMT results were similar, however. Conclusion: In the acute stroke phase, early integrated RAGT showed greater performance in gait rehabilitation than CRT and ELLT. Registration: ChiCTR1900026225.

Circ_0050908 up-regulates TRAF3 by sponging miR-324-5p to aggravate myocardial ischemia-reperfusion injury.

BACKGROUND: Aberrant circular RNAs (circRNAs) expression is closely associated with cardiovascular diseases. However, the regulatory functions of circRNAs in myocardial ischemia-reperfusion (I/R) injury remain largely undefined. METHODS: We established myocardial I/R model in vitro by oxygen and glucose deprivation and reperfusion in cardiomyocytes. The expression of circ_0050908, microRNA (miR)-324-5p, and TNF receptor-associated factor (TRAF3) was detected using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. The apoptosis was assayed by flow cytometry and Western blot. The activity of interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF-α), lactate dehydrogenase (LDH), creatine kinase myocardial band (CK-MB), CK, and superoxide dismutase (SOD) was evaluated using the relative commercial kits. Reactive oxygen species (ROS) detection was conducted using Dihydroethidium (DHE) staining. The interactions between miR-324-5p and circ_0050908 or TRAF3 were determined by dual-luciferase activity, RNA immunoprecipitation (RIP), and pull-down assays. RESULTS: I/R stimulation up-regulated circ_0050908 expression in cardiomyocytes. Functional experiments suggested that circ_0050908 knockdown led to the rescue of apoptosis enhancement, inflammation, and oxidative stress induced by I/R in cardiomyocytes. Mechanistically, circ_0050908 directly targeted miR-324-5p, and miR-324-5p inhibition reversed the inhibitory action of circ_0050908 knockdown on myocardial I/R injury. TRAF3 was verified to be a target of miR-324-5p, and miR-324-5p suppressed I/R-induced apoptosis, inflammatory response, and oxidative stress in cardiomyocytes through TRAF3. Besides that, circ_0050908 could regulate TRAF3 expression by miR-324-5p. CONCLUSION: Circ_0050908 knockdown protects cardiomyocytes against I/R injury by reducing apoptosis, inflammatory response, and oxidative stress through miR-324-5p/TRAF3 axis, revealing a novel therapeutic strategy for preventing myocardial I/R injury.

Nystagmus Parameters of Supine Roll Test Correlates With Prognosis After Repositioning Maneuver in Horizontal Semicircular Canal Benign Paroxysmal Positional Vertigo.

Background: Positional nystagmus induced by supine roll test is characteristic for diagnosing horizontal semicircular canal benign paroxysmal positional vertigo (HC-BPPV). In this study, we aimed to explore the value of nystagmus parameters in by supine roll test (SRT) as prognostic factors in HC-BPPV. Methods: We retrospectively analyzed the nystagmus parameters of 813 patients diagnosed with HC-BPPV by the SRT model in the SRM-IV system through video nystagmography. Then we used the computer-controlled canalith repositioning procedure (CCRP) mode for treatment. Based on the outcomes, patients were divided into either the cured group or the resistant group. The 1:1 propensity score matching (PSM) was applied to minimize potential selection bias. Then univariable and multivariable analyses were performed to identify the association of nystagmus parameters and the efficacy of CCRP. Results: Among the 813 patients, 99 (12.2%) were classified in the resistant group. The right side of HC-BPPV patients was twice the number of the left side patients (537 vs. 276). PSM is used to pair resistant patients to the cured patients, in which 99 pairs were successfully matched. Results of univariate and multivariate analyses showed that patients in the resistant group have longer latency in the affected side [odds ratio (OR) = 1.231 (1.110-1.366); P < 0.001] and slower slow phase velocity (SPV) in the healthy side [OR = 0.957 (0.917-0.999); P = 0.045]. Conclusion: Nystagmus parameters may represent the characteristics of canalith. HC-BPPV patients with a longer latency in the affected side and slower SPV on the healthy side during SRT have a higher risk of HC-BPPV persisting after a single CCRP.

Injection rate of contrast medium affects diagnostic ability of dynamic contrast-enhanced magnetic resonance imaging for endometrial carcinoma: a prospective cohort study.

BACKGROUND: Dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) can obtain semi-quantitative or quantitative parameters of tumors by capturing the images before and after injection of contrast medium. However, there has been no further research on the effect of flow rate of contrast medium on image quality and parameter sensitivity of DCE-MRI in endometrial carcinoma (EC). METHODS: This was a prospective cohort study enrolling patients who were suspected of EC between January 2018 and June 2020. The baseline data of participants were collected. Post-surgical histological examination acted as the gold standard of EC diagnosis and some characteristics of tumors were recorded. We calculated 3 important parameters of DCE-MRI, including volume transfer constant (Ktrans), flux rate constant (Kep), and extravascular extracellular volume fraction (Ve), according to the MRI system. The image quality in DCE-MRI imaging was evaluated according to contrast, resolution, artifact, signal-to-noise ratio, and scanning time. To evaluate the diagnostic ability of DCE-MRI with different injection rate, receiver operating characteristic (ROC) curve was generated and the area under curve (AUC) was calculated. RESULTS: According to the different injection rate of contrast medium, participants were divided into three groups, including 2, 3, and 4 mL/s group. It was found that there were more grade 1 EC in the 3 mL/s group (52.4%) than other two groups (34.3% and 23.3%, respectively), and the difference was significant (P=0.021). No other significant differences were found among all other variables. It was found that Ktrans was much higher in the 4 mL/s group than in other two groups (P<0.001). Also, Ve was much higher in the 4 mL/s group than in other two groups (P<0.001). However, no significant difference was found in Kep between three groups (P=0.633). Besides, the 4 mL/s group had the highest quality of all three groups (P<0.001). The sensitivity, specificity, and accuracy were highest in 4 mL/s group. The AUC in three groups were 0.822, 0.832, and 0.888 in the 2, 3, and 4 mL/s group, respectively. CONCLUSIONS: The DCE-MRI measurement is useful for the diagnosis of EC, and faster injection rate may be beneficial to improve diagnostic accuracy and image quality.

Up-regulation of CTRP12 ameliorates hypoxia/re-oxygenation-induced cardiomyocyte injury by inhibiting apoptosis, oxidative stress, and inflammation via the enhancement of Nrf2 signaling.

C1q/TNF-related protein 12 (CTRP12) has been reported to play a key role in coronary artery disease. However, whether CTRP12 plays a role in the regulation of myocardial ischemia-reperfusion injury is not fully understood. The goals of this work were to assess the possible relationship between CTRP12 and myocardial ischemia-reperfusion injury. Here, we exposed cardiomyocytes to hypoxia/re-oxygenation (H/R) to establish an in vitro cardiomyocyte injury model of myocardial ischemia-reperfusion injury. Our results showed that H/R treatment resulted in a decrease in CTRP12 expression in cardiomyocytes. The up-regulation of CTRP12 ameliorated H/R-induced cardiomyocyte injury via the down-regulation of apoptosis, oxidative stress, and inflammation. In contrast, the knockdown of CTRP12 enhanced cardiomyocyte sensitivity to H/R-induced cardiomyocyte injury. Further investigation showed that CTRP12 enhanced the levels of nuclear Nrf2 and increased the expression of Nrf2 target genes in cardiomyocytes exposed to H/R. However, the inhibition of Nrf2 markedly diminished CTRP12-overexpression-mediated cardioprotective effects against H/R injury. Overall, these data indicate that CTRP12 protects against H/R-induced cardiomyocyte injury by inhibiting apoptosis, oxidative stress, and inflammation via the enhancement of Nrf2 signaling. This work suggests a potential role of CTRP12 in myocardial ischemia-reperfusion injury and proposes it as an attractive target for cardioprotection.

Anti-arrhythmic and anti-heart failure effects of low-level electrical stimulation on aortic root ventricular ganglionated plexi.

BACKGROUND: It remains uncertain whether low-level electrical stimulation (LL-ES) of the ventricular ganglionated plexi (GP) improves heart function. This study investigated the anti-arrhythmic and anti-heart failure effects of LL-ES of the aortic root ventricular GP (ARVGP). METHODS: Thirty dogs were divided randomly into control, drug, and LL-ES groups after performing rapid right ventricular pacing to establish a heart failure (HF) model. The inducing rate of arrhythmia; levels of bioactive factors influencing HF, including angiotensin II type I receptor (AT-1R), transforming growth factor-beta (TGF-ß), matrix metalloproteinase (MMP), and phosphorylated extracellular signal-regulated kinase (p-ERK1/2); left ventricular stroke volume (LVSV), and left ventricular ejection fraction (LVEF)were measured after treatment with placebo, drugs, and LL-ES. RESULTS: The inducing rate of atrial arrhythmia decreased from 60% in the control group to 50% in the drug group and 10% in the LL-ES group (p = .033 vs. drug group) after 1 week of treatment. The ventricular effective refractory period was prolonged from 139 ± 8 ms in the drug group to 166 ± 13 ms in the LL-ES group (p = .001). Compared to the drug group, the expressions of AT-1R, TGF-ß, and MMP proteins were down-regulated in the LL-ES group, whereas that of p-ERK1/2 was significantly increased (all p = .001). Moreover, in the LL-ES group, LVSV increased markedly from 13.16 ± 0.22 to 16.86 ± 0.27 mL, relative to that in the drug group (p = .001), and LVEF increased significantly from 38.48% ± 0.53% to 48.94% ± 0.57% during the same time frame (p = .001). CONCLUSION: Short-term LL-ES of ARVGP had both anti-arrhythmic and anti-inflammatory effects and contributed to the treatment of tachycardia-induced HF and its associated arrhythmia.

Long-Term Safety and Efficacy of Antiplatelet Therapy in Patients With Cerebral Infarction With Thrombocytopenia.

This study aimed to investigate the long-term safety and benefits of antiplatelet therapy in patients with cerebral infarction with thrombocytopenia, as evidence regarding this was limited. This cohort trial assessed patients with acute cerebral infarction with thrombocytopenia treated in the Neurology Department of Shanghai Tenth People's Hospital from January 2016 to December 2018, and enrolled patients were followed up for 9 months. The patients were divided into non-antiplatelet and antiplatelet groups based on the actual intake of antiplatelet drugs. Primary endpoints included hemorrhagic events, recurrence of cerebral infarction, and activity of daily living (ADL) score changes. To balance baseline clinical data, propensity score matching was applied, and there were finally 65 matched patients, including 30 and 35 in the antiplatelet and non-antiplatelet groups, respectively. There were no differences in hemorrhagic and cerebral infarction recurrence rates between the 2 groups. ADL score change was higher in the antiplatelet group than in the non-antiplatelet group (10 vs 5, p = 0.039). In multivariate regression analysis, antiplatelet therapy significantly predicted a positive change in ADL scores [B = 8.381, 95% confidence interval (0.56-16.19)]. In patients with acute cerebral infarction with thrombocytopenia, antiplatelet therapy could the improve the quality of life in the chronic stage.

Comparison of Three Instruments for Activity Disability in Acute Ischemic Stroke Survivors.

BACKGROUND: Disabilities in physical activity and functional independence affect the early rehabilitation of stroke survivors. Moreover, a good instrument for assessing activity disability allows accurate assessment of physical disability and assists in prognosis determination. OBJECTIVE: To compare three assessment tools for physical activity in acute-phase stroke survivors. METHODS: We conducted this prospective observational study at an affiliated hospital of a Medical University in Shanghai, China, from June 2018 to November 2019. We administered three instruments to all patients during post-stroke days 5-7, including the Modified Barthel Index (MBI), Instrumental Activities of Daily Living (IADL), and modified Rankin scale (mRs). We analyzed correlations among the aforementioned scales and the National Institutes of Health Stroke Scale (NIHSS) using Spearman's rank-order correlations test. Univariate analyses were performed using the Mann-Whitney U test. We used a binary logistic regression model to assess the association between the NIHSS (30 days) and patient-related variables. Finally, we used receiver operating characteristic (ROC) curves to assess the predictive value of the multivariate regression models. RESULTS: There was a high correlation among the three instruments; furthermore, the MBI had a higher correlation with the NIHSS (days 5-7). The NIHSS (day 30) was correlated with thrombolysis. ROC analysis revealed that the mRs-measured disability level had the highest predictive value of short-term stroke severity (30 days). CONCLUSION: The MBI was the best scale for measuring disability in physical activity, whereas the mRs showed better accuracy in short-term prediction of stroke severity.

Inhibition of sphingomyelin synthase 2 relieves hypoxia-induced cardiomyocyte injury by reinforcing Nrf2/ARE activation via modulation of GSK-3ß.

Sphingomyelin synthase 2 (SMS2) is a vital contributor to tissue injury and affects various pathological processes. However, whether SMS2 participates in the modulation of cardiac injury in myocardial infarction has not been determined. This study aimed to evaluate the potential role of SMS2 in the regulation of cardiomyocyte injury induced by hypoxia, an in vitro model for studying myocardial infarction. Our data revealed that SMS2 expression was significantly upregulated in cardiomyocytes in response to hypoxia. Loss-of-function experiments revealed that knockdown of SMS2 markedly restored the viability of cardiomyocytes impaired by hypoxia, and attenuated hypoxia-evoked apoptosis and reactive oxygen species (ROS) generation. In contrast, cardiomyocytes that highly expressed SMS2 were more sensitive to hypoxia-induced injury. Moreover, SMS2 deficiency enhanced the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling through inactivation of glycogen synthase kinase-3ß. Notably, suppression of Nrf2 markedly abrogated SMS2 knockdown-mediated cardioprotective effects on hypoxia-exposed cardiomyocytes. Our results illustrate that downregulation of SMS2 exerts a cardioprotective function by protecting cardiomyocytes from hypoxia-induced apoptosis and oxidative stress through enhancement of Nrf2 activation. Our study indicates a potential role of SMS2 in the modulation of cardiac injury, which may contribute to the progression of myocardial infarction.

Prognosis of Neurological Improvement in Inpatient Acute Ischemic Stroke Survivors: A Propensity Score Matching Analysis.

OBJECTIVES: Stroke has become a national concern in China. Early prediction of stroke benefits patients and aids medical professionals in clinical decision making and rehabilitation plans to improve successful outcomes. To identify prediction factors influencing short-term outcomes in patients with acute ischemic stroke (AIS). MATERIALS AND METHODS: This was a hospital-based prospective observational study. Recovery of neurological improvement was represented by a percent reduction in the National Institutes of Health Stroke Scale (NIHSS) at discharge. We performed propensity score matching (PSM) to balance the NIHSS at admission and compared NIHSS scores before and after matching with PSM criteria. Finally, we assessed the prognosis of neurological improvement and patient-related variables. RESULTS: In the matched cohort, 92 pairs were matched by NIHSS admission after PSM. Modified Barthel Index, modified Rankin scale, NIHSS on admission, hypertension, sleep time, and Montreal Cognitive Assessment (MoCA) were statistically different between the two groups (P<0.05) before matching. Multivariable analysis identified two factors independently associated with neurological improvement: diabetes (P=0.030; adjusted odds ratio, 2.129; 95% confidence interval [CI] 1.078-4.026) and MoCA (P<0.001; adjusted odds ratio, 5.385; 95% CI 2.278-12.730). CONCLUSION: Consistent with previous studies, diabetes affected the short-term outcomes of AIS, while cognitive impairment had a negative effect on long-term AIS prognosis.Diabetes and early cognitive impairment have adverse effects on short-term prognosis after AIS.

Multidimensional intervention in individuals with mild cognitive impairment: a pilot nonrandomized study.

BACKGROUND: There is an increasing need for non-pharmacological treatments that can enhance the cognitive function of individuals with mild cognitive impairment. We firstly performed multidimensional intervention based on the concept of the International Classification of Functioning, Disability and Health, and aimed to explore its short-term effect on the improvement of cognitive function in individuals with mild cognitive impairment. METHODS: Twenty-four individuals with mild cognitive impairment in this pilot study were recruited from the memory clinic and neurology ward in Shanghai Tenth People's Hospital from August 2018 to August 2019. According to participants' personal wishes, 13 and 11 participants were enrolled into an intervention group and a control group, respectively. Based on the International Classification of Functioning, Disability and Health, we performed baseline assessments to all participants. According to the assessment results and the wishes and hobbies of the patients, then doctors, therapists, nurses, patients and their families together chose the appropriate multidimensional interventions to the intervention group in seven 1-hour sessions and health education to the both groups. After one week, all participants underwent reevaluation of cognitive function. RESULTS: There were significant differences between the two groups on the improvement of cognitive function. The intervention group (mean ± SD, 3.460±1.613) scored higher than the control group (1.360±0.924) on the change score of the total score in the Montreal Cognitive Assessment (t =3.808, P<0.001, 95% CI: 0.955-3.240), though not on the change score of any cognitive domain score. Regression results showed that the change score of the total score was negatively correlated with the baseline score of Abstraction score (aR2 =0.583, ß =-0.506, P=0.031) and the modified Barthel index score (ß =-0.464, P=0.045) in the intervention group. CONCLUSIONS: The pilot study demonstrated that the short-term multidimensional intervention may produce cognitive benefits in individuals with mild cognitive impairment.

A new photochromic Gd-MOF with photoswitchable bluish-white to greenish-yellow emission based on electron transfer.

Utilization of photochromism in photo-switchable white-light emitters (WLEs) is a challenging task. In an effort to achieve this, we have recently developed a new Gd-MOF using a photoactive pyridinium-based inner salt. The compound shows interesting photoswitchable bluish white light to greenish yellow light emission as a result of electron transfer, a phenomenon that has not been observed previously in photochromic crystal compounds.

Downregulation of FOXO6 alleviates hypoxia-induced apoptosis and oxidative stress in cardiomyocytes by enhancing Nrf2 activation via upregulation of SIRT6.

Forkhead box protein O6 (FOXO6) has been recently identified as a novel regulator of oxidative stress in multiple pathological processes. However, whether FOXO6 participates in the regulation of oxidative stress of myocardial infarction is unclear. The present study was performed to evaluate the potential role of FOXO6 in regulating hypoxia-induced apoptosis and oxidative stress in cardiomyocytes in vitro. Our results demonstrated that FOXO6 expression was highly elevated in cardiomyocytes exposed to hypoxia. Downregulation of FOXO6 expression by the siRNA-mediated gene knockdown in hypoxia-exposed cardiomyocytes increased cell viability, while repressing apoptosis and reactive oxygen species (ROS) production. In contrast, overexpression of FOXO6 enhanced the sensitivity of cardiomyocytes to hypoxia-induced injury. Further, in-depth research revealed that knockdown of FOXO6 promoted the expression of sirtuin6 (SIRT6) and enhanced the activation of nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant signaling. Moreover, SIRT6 inhibition markedly blocked the FOXO6 knockdown-induced promotion effect on Nrf2 activation. In addition, Nrf2 inhibition partially reversed the FOXO6 knockdown-mediated protective effect against hypoxia-induced cardiomyocyte injury. Taken together, the findings of our study demonstrate that knockdown of FOXO6 is capable of protecting cardiomyocytes from hypoxia-induced apoptosis and oxidative stress by enhancing Nrf2 activation via upregulation of SIRT6. Our study highlights a potential role of FOXO6 in myocardial infarction and suggests it as an attractive target for cardioprotection.

Association between Dix-Hallpike test parameters and successful repositioning maneuver in posterior semicircular canal benign paroxysmal positional vertigo: a case-control study.

BACKGROUND: Nystagmus (i.e., involuntary eye movement) provoked by the Dix-Hallpike test (DHT) is considered the gold standard for diagnosing posterior semicircular canal benign paroxysmal positional vertigo (psc-BPPV). However, robust evidence regarding this diagnostic maneuver's treatment efficacy is still lacking. This study aimed to investigate the parameters of positional nystagmus in the DHT as prognostic factors for unilateral psc-BPPV. METHODS: We reviewed 357 patients with unilateral psc-BPPV who underwent the computer-controlled canalith repositioning procedure (CCRP), which mimics the Epley maneuver. Additionally, positional nystagmus in the DHT was observed through a video-oculography. Patients were retrospectively divided into two groups according to resistance to the CCRP. Univariable and multivariable analyses were performed on age, gender, blood pressure, and nystagmus parameters of the affected side in the DHT in order to reveal associated factors causing resistance to the CCRP. RESULTS: With univariate and multivariate analysis, we observed a decrease in vertical time course during slow phase nystagmus on the affected side (odds ratio, OR 0.77, P=0.011 vs. OR 0.80, P=0.027). Moreover, an increased vertical velocity amplitude in the DHT during slow phase nystagmus (OR 3.16, P=0.029 vs. OR 2.96, P=0.035) remained an associated factor of maneuver resistance. CONCLUSIONS: Decreased canalith weight on the affected side was associated with resistance to the CCRP. This association corresponded to the observation that psc-BPPV patients with a decreased time course and increased velocity in the slow phase of recording nystagmus have a worse prognosis of their BPPV persisting after a single CCRP.

Red Blood Cell Indices in Relation to Post-stroke Psychiatric Disorders: A Longitudinal Study in a Follow-up Stroke Clinic.

BACKGROUND: Depression and anxiety after stroke are common conditions that are likely to be neglected. Abnormal red blood cell (RBC) indices may be associated with neuropsychiatric disorders. However, the association of RBC indices with post-stroke depression (PSD) and poststroke anxiety (PSA) has not been sufficiently investigated. METHODS: We aimed to investigate the trajectory of post-stroke depression and anxiety in our follow- up stroke clinic at 1, 3, and 6 months, and the association of RBC indices with these. One hundred and sixty-two patients with a new diagnosis of ischemic stroke were followed up at 1, 3, and 6 months, and underwent Patient Health Questionnaire-9 (PHQ-9) and the general anxiety disorder 7-item (GAD-7) questionnaire for evaluation of depression and anxiety, respectively. First, we used Kaplan-Meier analysis to investigate the accumulated incidences of post-stroke depression and post-stroke anxiety. Next, to explore the association of RBC indices with psychiatric disorders after an ischemic stroke attack, we adjusted for demographic and vascular risk factors using multivariate Cox regression analysis. RESULTS: Of the 162 patients with new-onset of ischemic stroke, we found the accumulated incidence rates of PSD (1.2%, 17.9%, and 35.8%) and PSA (1.2%, 13.6%, and 15.4%) at 1, 3, and 6 months, respectively. The incident PSD and PSA increased 3 months after a stroke attack. Multivariate Cox regression analysis indicated independent positive associations between PSD risk and higher mean corpuscular volume (MCV) (OR=1.42, 95% CI=1.16-1.76), older age (OR=2.63, 95% CI=1.16-5.93), and a negative relationship between male sex (OR=0.95, 95% CI=0.91-0.99) and PSA. CONCLUSION: The risks of PSD and PSA increased substantially 3 months beyond stroke onset. Of the RBC indices, higher MCV, showed an independent positive association with PSD.

PHLPP2 downregulation protects cardiomyocytes against hypoxia-induced injury through reinforcing Nrf2/ARE antioxidant signaling.

Cardiomyocyte injury induced by acute myocardial infarction contributes to myocardial dysfunction. Accumulating evidence has demonstrated that pleckstrin homology domain leucine-rich repeat protein phosphatase 2 (PHLPP2) is a cytoprotective protein that protects against various adverse injuries. However, whether PHLPP2 participates in regulating myocardial-infarction-induced cardiomyocyte injury remains unknown. In the present study, we aimed to investigate the biological role and molecular mechanism of PHLPP2 in regulating hypoxia-induced cardiomyocyte injury. Cardiomyocytes were cultured in an anaerobic chamber for 24 h to induce hypoxic injury in vitro. The expression of PHLPP2 was determined by real-time quantitative PCR and Western blot analysis. Cell viability was measured by MTT assay. Cell apoptosis was assessed by TUNEL and caspase-3 activity assays. Intracellular reactive oxygen species (ROS) levels were measured by DCFH-DA probe. PHLPP2 expression was highly upregulated in hypoxia-injured cardiomyocytes. Inhibition of PHLPP2 by small interfering RNA (siRNA)-mediated gene silencing significantly improved the viability of hypoxia-injured cardiomyocytes and attenuated hypoxia-induced apoptosis and ROS production. In contrast, PHLPP2 overexpression exacerbated hypoxia-induced apoptosis and ROS production in cardiomyocytes. Mechanism research revealed that PHLPP2 silencing increased the phosphorylation of glycogen synthase kinase (GSK)-3ß and promoted the nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2). In addition, PHLPP2 inhibition promoted Nrf2/antioxidant response element (ARE) transcriptional activity. However, Nrf2 silencing markedly reversed PHLPP2-inhibition-mediated cardioprotection, while GSK-3ß inhibition partially blocked the PHLPP2-overexpression-induced adverse effect. Taken together, these findings demonstrate that PHLPP2 inhibition alleviates hypoxia-induced cardiomyocyte injury by reinforcing Nrf2/ARE antioxidant signaling via inactivating GSK-3ß, a pathway that highlights the importance of the PHLPP2/GSK-3ß/Nrf2/ARE signaling axis in regulation of cardiomyocyte injury. Our study suggests a potential relevance for PHLPP2 in acute myocardial infarction, and this protein may serve as a promising target for cardioprotection.

E3 ubiquitin ligase siah­1 nuclear accumulation is critical for homocysteine­induced impairment of C6 astroglioma cells.

Elevated plasma homocysteine (Hcy), known as hyperhomocysteinemia (HHcy), is an independent risk factor for neurodegenerative diseases. Hcy, even at a low concentration, can promote free radical formation and increase oxidative stress, leading to neuronal death, which may be an important mechanism underlying the pathogenesis of neurodegenerative diseases. Although several reports have indicated that the nuclear translocation of glyceraldehyde 3­phosphate dehydrogenase (GAPDH) may be involved in Hcy­induced apoptosis, the exact mechanism remains to be fully elucidated. The siah E3 ubiquitin protein ligase 1 (siah­1) gene was found to be critical for the translocation of GAPDH from the cytoplasm to the nucleus. In the present study, the role of siah­1 was investigated in the nuclear translocation of GAPDH in rat C6 astroglioma cells treated with Hcy. C6 cells were treated with various concentrations of Hcy for 48 h and the expression level of siah­1 was examined using reverse transcription­quantitative polymerase chain reaction and western blotting analysis. In addition, the subcellular localization of siah­1 and GAPDH and the interaction between these two factors were investigated by immunofluorescence staining and co­immunoprecipitation assay, respectively. The results showed that Hcy at a high concentration increased the expression of siah­1 and induced nuclear translocation of siah­1 and GAPDH. In addition, siah­1 knockdown by siah­1 small interfering RNA significantly decreased the Hcy­induced nuclear accumulation of GAPDH and inhibited the impairment of C6 cells. These findings suggest that siah­1 is involved in Hcy­induced cell damage by promoting the nuclear translocation of GAPDH.

Patient and Family Caregiver's Neuroticism and Conscientiousness Personality in Relation to Quality of Life of Patient With Parkinson's Disease: A Cross-Sectional Study Neuroticism and Conscientiousness Personality in Relation to QoL of Patient With PD.

Background: Personality impacts life expectancy and comprehensive treatment efficacy for patients with Parkinson's disease (PD). However, current research fails to involve the family caregiver's personality despite significant external support provided by family caregivers. This study explored neuroticism and conscientiousness personality factors of the patient and family caregiver associated with quality of life (QoL) of PD patients. Methods: 134 couples of patients presenting with PD and their family caregivers that met inclusion criteria, were recruited for this cross-sectional study at Shanghai Tenth People's Hospital from October 2015 to 2017. The Parkinson's Disease Questionnaire-39 Items (PDQ-39) for QoL, including the physical component summary (PCS) and mental component summary (MCS), the Neuroticism Extraversion Openness Five-Factor Inventory (NEO-FFI) for neuroticism and conscientiousness personalities, and the Unified Parkinson's Disease Rating Scale (UPDRS) for PD severity questionnaires were employed. Multivariate stepwise linear regression determined the contributions of demographic, clinical and personality variables in PDQ-39, PCS, and MCS. Results: PD patients and neuroticism were significantly associated with total PDQ-39, PCS, and MCS. Additionally, conscientiousness was significantly associated with PDQ-39 and PCS. After adding neuroticism and caregiver conscientiousness personality, the importance of neuroticism for the QoL model dramatically decreased, and caregiver conscientiousness personality was associated with lower scores in total PDQ-39 and PCS. Conclusion: We revealed a significant association between neuroticism and physical or mental status of PD patients; however, this association decreased when caregiver conscientiousness was added to the model. Moreover, conscientiousness of patients and caregivers were associated with improved QoL.