Association between high-resolution magnetic resonance vessel wall imaging characteristics and recurrent stroke in patients with intracranial atherosclerotic steno-occlusive disease: A prospective multicenter study.

BACKGROUND: High-resolution magnetic resonance vessel wall imaging (HRMR-VWI) is a promising technique for identifying intracranial vulnerable plaques beyond lumen narrowing. However, the association between HRMR-VWI characteristics and recurrent stroke remains uncertain. AIMS: This study aimed to investigate the association between HRMR-VWI characteristics and recurrent ipsilateral stroke in patients with symptomatic intracranial atherosclerotic steno-occlusive disease (ICAS). METHODS: This multicenter, observational study recruited first-ever acute ischemic stroke patients attributed to ICAS (>50% stenosis or occlusion) within 7 days after onset. Participants were assessed by multiparametric magnetic resonance imaging (MRI) including diffusion-weighted imaging, three-dimension time-of-flight magnetic resonance angiography, and three-dimensional T1-weighted HRMR-VWI. The patients were recommended to receive best medical therapy and were systematically followed up for 12 months. The association between HRMR-VWI characteristics and the time to recurrent ipsilateral stroke was investigated by univariable and multivariable analysis. RESULTS: Two hundred and fifty-five consecutive patients were enrolled from 15 centers. The cumulative 12 month ipsilateral recurrence incidence was 4.1% (95% confidence interval (CI): 1.6-6.6%). Patients with recurrent ipsilateral stroke exhibited higher rates of intraplaque hemorrhage (IPH) (30.0% vs 6.5%) and eccentric plaque (90.0% vs 48.2%), and lower occurrence of occlusive thrombus (10.0% vs 23.7%). Plaque length (5.69 ± 2.21 mm vs 6.67 ± 4.16 mm), plaque burden (78.40 ± 7.37% vs 78.22 ± 8.32%), degree of stenosis (60.25 ± 18.95% vs 67.50% ± 22.09%) and remodeling index (1.07 ± 0.27 vs 1.03 ± 0.35) on HRMR-VWI did not differ between patients with and without recurrent ipsilateral stroke. In the multivariable Cox regression analysis, IPH (hazard ratio: 6.64, 95% CI: 1.23-35.8, p = 0.028) was significantly associated with recurrent ipsilateral stroke after adjustment.Conclusions:Our results suggest intraplaque hemorrhage (IPH) is significantly associated with recurrent ipsilateral stroke and has potential value in the selection of patients for aggressive treatment strategies. DATA ACCESS STATEMENT: Data from this study are available and can be accessed upon request.

Comorbidity in patients with first-ever ischemic stroke: Disease patterns and their associations with cognitive and physical function.

The present study examined the prevalence and pattern of comorbidity among Chinese patients with first-ever acute ischemic stroke, and assessed the associations of specific comorbidity patterns with physical and cognitive functioning after stroke occurrence. A hospital-based cross-sectional study was conducted among 2,151 patients with first-ever ischemic stroke (age ≥40 years; 64.2% men) who were admitted to two university hospitals in Shandong, China between 2016 and 2017. Data on demographics, lifestyles, chronic health conditions, and use of medications were collected through in-person interviews, clinical examinations, and laboratory tests. Physical functioning was assessed by the Barthel index (BI) and the modified Rankin Scale (mRS) while cognitive functioning was assessed by the Montreal Cognitive Assessment test. The results showed that comorbidity was present in 90.9% of the stroke patients (women vs. men: 95.2 vs. 88.7%, P < 0.001). Exploratory factor analysis identified three patterns of comorbidity, i.e., patterns of degenerative-cardiopulmonary, heart-gastrointestinal-psychiatric, and metabolic-kidney diseases. The number of comorbidities was significantly associated with a higher likelihood of moderate-to-severe physical dependence [odds ratio (95% CI) = 1.15 (1.06-1.25) for BI and 1.12 (1.04-1.21) for mRS, all P < 0.01] and cognitive impairment [odds ratio (95% CI) = 1.11 (1.02-1.20), P = 0.017], after adjusting for multiple covariates. Almost all the three comorbidity patterns were associated with increased likelihoods of physical dependence (range for odds ratios: 1.26-1.33) and cognitive impairment (range for odds ratios: 1.25-1.34). No significant association was found between degenerative-cardiopulmonary pattern and mRS. These findings suggest that comorbidity is associated with poor physical and cognitive functioning during the acute phase of ischemic stroke. Routine assessments of comorbidity and cognitive and physical function among patients with acute ischemic stroke should be considered in stroke research and clinical practice.

Predictive values of carotid high-resolution magnetic resonance imaging for large embolus shedding in carotid artery stenting.

BACKGROUND: Embolus shedding is one of the important complications in carotid artery stenting (CAS). Carotid high-resolution magnetic resonance imaging (HR-MRI) is often used to directly reflect important biological characteristics, such as plaque size and composition, as well as the structure of the carotid artery wall. The aim of this study was to investigate the predictive values of carotid HR-MRI for large embolus shedding in CAS. METHODS: In total, 195 patients with carotid stenosis were enrolled. Preoperative carotid HR-MRI was performed to define the nature of the carotid plaques. CAS was performed in all patients, and intraoperative embolic protection devices were used to collect the shed emboli. According to the diameter and number of shed emboli, the patients were divided into the small-embolus group (group X) and largeembolus group (group Y). Logistic regression analysis was used to analyze the risk factors of large embolus shedding. RESULTS: Group Y included 58 patients, and group X included 137 patients. Age, stenosis length, smoking, and ≥3 transient cerebral ischemic attacks were risk factors for large embolusshedding. Two cases of shed large emboli developed from stable plaques, and 56 cases of large emboli developed from vulnerable plaques. When vulnerable plaques were associated with more risk factors, the incidences of large embolus shedding in cases with vulnerable plaques combined with 0, 1, 2, 3, and 4 risk factors were 44 % (4/9), 68.1% (15/22), 72.2% (13/18), 76.5% (13/17), and 84.6% (11/13), respectively. DISCUSSION: Carotid HR-MRI can predict the incidence of large embolus shedding in CAS.

Stroke incidence and cognitive outcomes of intracranial atherosclerotic stenosis: study protocol for a multicenter, prospective, observational cohort study.

Background: Intracranial atherosclerotic stenosis (ICAS) is one of the leading causes of stroke worldwide. Current diagnostic evaluations and treatments remain insufficient to assess the vulnerability of intracranial plaques and reduce the recurrence of stroke in symptomatic ICAS. On the other hand, asymptomatic ICAS is associated with an increased risk of cognitive impairment. The pathogenesis of ICAS related cognitive decline is largely unknown. The aim of SICO-ICAS study (stroke incidence and cognitive outcomes of ICAS) is to elucidate the pathophysiology of stroke and cognitive impairment in ICAS population, comprehensively evaluating the complex interactions among life-course exposure, genomic variation, vascular risk factors, cerebrovascular burden and coexisting neurodegeneration. Methods: SICO-ICAS is a multicenter, prospective, observational cohort study. We aim to recruit 3,000 patients with symptomatic or asymptomatic ICAS (>50% or occlusion) who will be followed up for ≥12 months. All participants will undergo pre-designed magnetic resonance imaging packages, blood biomarkers testing, as well as detailed cognitive domains assessment. All participants will undergo clinical visits every 6 months and telephone interviews every 3 months. The primary outcome measurement is ischemic stroke or cognitive impairment within 12 months after enrollment. Discussion: This study will establish a large prospective ICAS cohort, hopefully discover new biomarkers associated with vulnerable intracranial plaques, identify subjects at high risk for incident ischemic stroke or cognitive impairment, and eventually propose a precise diagnostic and treatment strategy for ICAS population. Trial Registration: Chinese Clinical Trials Register ChiCTR2200061938.

Metabolic syndrome in patients with first-ever ischemic stroke: prevalence and association with coronary heart disease.

The metabolic syndrome (MetS) has been well linked with coronary heart disease (CHD) in the general population, but studies have rarely explored their association among patients with stroke. We examine prevalence of MetS and its association with CHD in patients with first-ever ischemic stroke. This hospital-based study included 1851 patients with first-ever ischemic stroke (mean age 61.2 years, 36.5% women) who were hospitalized into two university hospitals in Shandong, China (January 2016-February 2017). Data were collected through interviews, physical examinations, and laboratory tests. MetS was defined following the National Cholesterol Education Program (NCEP) criteria, the International Diabetes Federation (IDF) criteria, and the Chinese Diabetes Society (CDS) criteria. CHD was defined following clinical criteria. Data were analyzed using binary logistic regression models. The overall prevalence of MetS was 33.4% by NECP criteria, 47.2% by IDF criteria, and 32.5% by CDS criteria, with the prevalence being decreased with age and higher in women than in men (p < 0.05). High blood pressure, high triglycerides, and low HDL-C were significantly associated with CHD (multi-adjusted odds ratio [OR] range 1.27-1.38, p < 0.05). The multi-adjusted OR of CHD associated with MetS defined by the NECP criteria, IDF criteria, and CDS criteria (vs. no MetS) was 1.27 (95% confidence interval 1.03-1.57), 1.44 (1.18-1.76), and 1.27 (1.03-1.57), respectively. In addition, having 1-2 abnormal components (vs. none) of MetS was associated with CHD (multi-adjusted OR range 1.66-1.72, p < 0.05). MetS affects over one-third of patients with first-ever ischemic stroke. MetS is associated with an increased likelihood of CHD in stroke patients.

Interleukin-17 Links Inflammatory Cross-Talks Between Comorbid Psoriasis and Atherosclerosis.

Psoriasis is a chronic, systemic, immune-mediated inflammatory disorder that is associated with a significantly increased risk of cardiovascular disease (CVD). Studies have shown that psoriasis often coexists with atherosclerosis, a chronic inflammatory disease of large and medium-sized arteries, which is a major cause of CVD. Although the molecular mechanisms underlying this comorbidity are not fully understood, clinical studies have shown that when interleukin (IL)-17A inhibitors effectively improve psoriatic lesions, atherosclerotic symptoms are also ameliorated in patients with both psoriasis and atherosclerosis. Also, IL-17A levels are highly expressed in the psoriatic lesions and atherosclerotic plaques. These clinical observations implicit that IL-17A could be a crucial link for psoriasis and atherosclerosis and IL-17A-induced inflammatory responses are the major contribution to the pathogenesis of comorbid psoriasis and atherosclerosis. In this review, the current literature related to epidemiology, genetic predisposition, and inflammatory mechanisms of comorbidity of psoriasis and atherosclerosis is summarized. We focus on the immunopathological effects of IL-17A in both diseases. The goal of this review is to provide the theoretical base for future preventing or treating psoriasis patients with atherosclerosis comorbidity. The current evidence support the notion that treatments targeting IL-17 seem to be hold some promise to reduce cardiovascular risk in patients with psoriasis.

Clinical characteristics of anti-N-methyl-D-aspartate receptor encephalitis in patients with a long-term history of mental disorders.

BACKGROUND: Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is an autoimmune disorder characterized by complex neuropsychiatric syndromes during disease onset. Although this disease has been well documented in the last decade, clinical characteristics of anti-NMDA receptor encephalitis in patients with long-term diagnostic history of mental disorders remain unclear. METHODS: Here, we reviewed and analyzed series of anti-NMDA receptor encephalitis patients with a long-term medical history of psychiatric disorders through a review of literature using PubMed, web of science and Embase database. In addition, we described a patient of anti-NMDA receptor encephalitis with a long-term history of major depressive disorder. RESULTS: A total of 14 patients with anti-NMDA receptor encephalitis and a long-term history of mental disorders were included in our study. We found that most patients were adult (92.9%) and female (78.6%). These patients often first visited a psychiatric department (71.43%). The mean disease course of psychiatric disorders was more than 9 years. Speech impairment (71.4%), abnormal behaviors (64.3%), and catatonia (64.3%) were the most common clinical symptoms. Most patients (85.7%) had a satisfactory prognosis after immunotherapy. CONCLUSION: Anti-NMDA receptor encephalitis in individuals with mental disorders is an underestimated condition, yet it presents complex clinical symptoms. Mental and behavioral impairments are more frequently observed in newly diagnosed anti-NMDA receptor encephalitis patients with a long-term history of mental disorders than those without mental illness. A diagnosis of anti-NMDA receptor encephalitis should be considered when patients with mental illness show sudden fluctuations in psychiatric symptoms.

Mild encephalitis/encephalopathy with a reversible splenial lesion associated with respiratory syncytial virus infection in infants.

Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is a clinicoradiologic syndrome typically characterized by transient mild encephalitis or encephalopathy with reversible lesions being found in the splenium of corpus callosum (SCC) by magnetic resonance imaging (MRI). A variety of pathogens including influenza virus, rotavirus, and adenovirus associated with MERS have been reported. However, respiratory syncytial virus (RSV)-related MERS is relatively rare in infants. In this study, we report two Chinese infants who suffered from RSV-related MERS. Both infants manifested as fever, seizure, and altered states of consciousness with confirmed detections of RSV-RNA in the specimens from throat swab. Clinical symptoms/signs such as apnea and shallow breathing were also noted in these two infants. Furthermore, brain MRI images indicated reversible isolated lesions with transiently reduced diffusion in the SCC. Fortunately, both of these two infants recovered completely following treatment within a month. Our study suggests that RSV may serve as a novel causative agent for MERS in infants. Clinicians should focus more attention on RSV-related MERS in infants in order to improve early accurate diagnosis and therapeutic decision making.

Health-related quality of life after first-ever acute ischemic stroke: associations with cardiovascular health metrics.

PURPOSE: To investigate the associations between cardiovascular health (CVH) metrics and health-related quality of life (HRQL) among patients with ischemic stroke in China, and further explore the role of physical and cognitive function in their associations. METHODS: This hospital-based study included 1714 patients with first-ever acute ischemic stroke (age ≥ 40 years; 36.7% women) who were admitted to two university hospitals in Shandong, China. We collected information on seven CVH metrics (smoking, body mass index, diet, physical activity, blood pressure, total cholesterol, and fasting blood glucose) through interviews, clinical examinations, and laboratory tests. EQ-5D-3L was used to assess HRQL. Cognitive and physical functioning was assessed by the Montreal Cognitive Assessment test and Barthel index, respectively. Data were analyzed using the general linear regression models. RESULTS: The average score (SD) was 0.746 (0.23) for HRQL index and 72.7 (15.8) for self-rated health. Optimal levels of four individual CVH metric components (diet, physical activity, blood pressure, and blood glucose) and a higher composite CVH score were significantly associated with a greater HRQL index and better self-rated health (p < 0.05 for all). Physical dependence and cognitive impairment were associated with a lower HRQL index and poorer self-rated health status (p < 0.001). Furthermore, the relationships between CVH metrics and HRQL index varied by functional status, such that their associations were statistically significant only among people who had physical dependence or cognitive impairment. CONCLUSION: Achieving a better cardiovascular health profile is associated with better quality of life among ischemic stroke survivors, primarily in those with physical or cognitive impairment.

Neurotrophin-3 Promotes the Neuronal Differentiation of BMSCs and Improves Cognitive Function in a Rat Model of Alzheimer's Disease.

Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) has the potential to be developed into an effective treatment for neurodegenerative diseases such as Alzheimer's disease (AD). However, the therapeutic effects of BMSCs are limited by their low neural differentiation rate. We transfected BMSCs with neurotrophin-3 (NT-3), a neurotrophic factor that promotes neuronal differentiation, and investigated the effects of NT-3 gene overexpression on the differentiation of BMSCs into neurons in vitro and in vivo. We further studied the possible molecular mechanisms. We found that overexpression of NT-3 promoted the differentiation of BMSCs into neurons in vitro and in vivo and improved cognitive function in rats with experimental AD. By contrast, silencing NT-3 inhibited the differentiation of BMSCs and decreased cognitive function in rats with AD. The Wnt/ß-catenin signaling pathway was involved in the mechanism by which NT-3 gene modification influenced the neuronal differentiation of BMSCs in vitro and in vivo. Our findings support the prospect of using NT-3-transduced BMSCs for the development of novel therapies for AD.

Design of stroke imaging package study of intracranial atherosclerosis: a multicenter, prospective, cohort study.

BACKGROUND: Intracranial atherosclerosis (ICAS) is a major cause of stroke worldwide. However, much remains unknown regarding its underlying pathophysiology. High-resolution magnetic resonance imaging (HR-MRI) can clearly display intracranial vessel wall lesions in vivo. The aim of stroke imaging package study of ICAS (SIPS-ICAS) study is to explore the stroke mechanisms of symptomatic ICAS, the dynamic changes under aggressive medical treatment and their associations with clinical events using conventional MRI sequences plus HR-MRI. METHODS: This is a multicenter, prospective, cohort study recruiting first-ever acute ischemic stroke patients attributed to intracranial large artery stenosis (>50% or occlusion). Subjects undergo a pre-designed stroke imaging packages at baseline and are recommended to receive aggressive medical treatments. Participants will be followed up for functional outcome, stroke recurrence, and death events at 3, 6 and 12 months and retake HR-MRI imaging at 6 months. RESULTS: Enrollment began in November 2018 and 96 patients have been enrolled as of September 2019. CONCLUSIONS: The SIPS-ICAS study will provide insights into the pathophysiology of ICAS and identify specific imaging markers for risk stratification and prognosis prediction. At the same time, the feasibility and validity of the new stroke imaging package including HR-MRI will be assessed, which is promising for clinical routine use.

Efficacy of cattle encephalon glycoside and ignotin in patients with acute cerebral infarction: a randomized, double-blind, parallel-group, placebo-controlled study.

Cattle encephalon glycoside and ignotin (CEGI) injection is a compound preparation formed by a combination of muscle extract from healthy rabbits and brain gangliosides from cattle, and it is generally used as a neuroprotectant in the treatment of central and peripheral nerve injuries. However, there is still a need for high-level clinical evidence from large samples to support the use of CEGI. We therefore carried out a prospective, multicenter, randomized, double-blind, parallel-group, placebo-controlled study in which we recruited 319 patients with acute cerebral infarction from 16 centers in China from October 2013 to May 2016. The patients were randomized at a 3:1 ratio into CEGI (n = 239; 155 male, 84 female; 61.2 ± 9.2 years old) and placebo (n = 80; 46 male, 34 female; 63.2 ± 8.28 years old) groups. All patients were given standard care once daily for 14 days, including a 200 mg aspirin enteric-coated tablet and 20 mg atorvastatin calcium, both taken orally, and intravenous infusion of 250-500 mL 0.9% sodium chloride containing 40 mg sodium tanshinone IIA sulfonate. Based on conventional treatment, patients in the CEGI and placebo groups were given 12 mL CEGI or 12 mL sterile water, respectively, in an intravenous drip of 250 mL 0.9% sodium chloride (2 mL/min) once daily for 14 days. According to baseline National Institutes of Health Stroke Scale scores, patients in the two groups were divided into mild and moderate subgroups. Based on the modified Rankin Scale results, the rate of patients with good outcomes in the CEGI group was higher than that in the placebo group, and the rate of disability in the CEGI group was lower than that in the placebo group on day 90 after treatment. In the CEGI group, neurological deficits were decreased on days 14 and 90 after treatment, as measured by the National Institutes of Health Stroke Scale and the Barthel Index. Subgroup analysis revealed that CEGI led to more significant improvements in moderate stroke patients. No drug-related adverse events occurred in the CEGI or placebo groups. In conclusion, CEGI may be a safe and effective treatment for acute cerebral infarction patients, especially for moderate stroke patients. This study was approved by the Ethical Committee of Peking University Third Hospital, China (approval No. 2013-068-2) on May 20, 2013, and registered in the Chinese Clinical Trial Registry (registration No. ChiCTR1800017937).

Prevalence and associated factors of poor sleep quality among Chinese older adults living in a rural area: a population-based study.

OBJECTIVE: To investigate the prevalence and associated factors of poor sleep quality among community-dwelling elderly population in a rural area of Northern China. METHODS: We conducted a cross-sectional survey in August-December 2014 and recruited 2195 participants who were aged 65 years or older and living in Yanlou Town of Yanggu County in western Shandong Province, China. Data on demographics, health-related behaviors, and clinical conditions were collected through structured interviews. The Pittsburgh Sleep Quality Index (PSQI) was used to assess the sleep quality and patterns. Poor sleep quality was defined as a PSQI score > 7. We employed multiple logistic models to relate poor sleep quality to various factors. RESULTS: The overall prevalence rates of poor sleep quality were 33.8% in the total sample, 39.2% in women and 26.3% in men (P < 0.01). The most common abnormal sleep domains were prolonged sleep latency (39.7%), decreased sleep duration (31.0%), and reduced habitual sleep efficiency (28.8%). Multiple logistic regression analyses revealed that poor sleep quality was significantly associated with female sex (OR = 1.76, 95% CI 1.46-2.12) and clinical comorbidities such as hypertension (OR = 1.28, 95% CI 1.06-1.54), coronary heart disease (OR = 1.60, 95% CI 1.27-2.00), and chronic obstructive pulmonary disease (OR = 1.82, 95% CI 1.34-2.49). CONCLUSIONS: The sleep disorders were highly prevalent among the elderly in rural China. Modifiable risk factors such as cardiometabolic risk factors and disorders were associated with poor sleep quality, which might be potential targets for interventions to improve sleep quality in elderly population.

Treatment of migraines with Tianshu capsule: a multi-center, double-blind, randomized, placebo-controlled clinical trial.

BACKGROUND: Tianshu capsule (TSC), a formula of traditional Chinese medicine, has been widely used in clinical practice for prophylactic treatment of headaches in China. However, former clinical trials of TSC were small, and lack of a standard set of diagnostic criteria to enroll patients. The study was conducted to re-evaluate the efficacy and safety of TSC post-marketing in an extending number of migraineurs who have diagnosed migraine with the International Classification of Headache Disorders, 3rd edition (beta version, ICHD-3ß). METHODS: The study was a double-blind, randomized, placebo-controlled clinical trial that conducted at 20 clinical centers in China. At enrollment, patients between 18 and 65 years of age diagnosed with migraine were assigned to receive either TSC (4.08 g, three times daily) or a matched placebo according to a randomization protocol. The primary endpoint was a relative reduction of 50% or more in the frequency of headache attacks. The secondary outcomes included a reduction in the incidence of headache, the visual analogue scale of headache attacks, days of acute analgesic usage, and percentage of patients with a decrease of 50% or more in headache severity. Accompanying symptoms were also assessed. RESULTS: One thousand migraine patients were initially enrolled in the study, and 919 of them completed the trial. Following the 12-week treatment, significant improvement was observed in the TSC group concerning both primary and secondary outcomes. After therapy discontinuation, the gap between the TSC group and the placebo group in efficacy outcomes continued to increase. There were no severe adverse effects. CONCLUSIONS: TSC is an effective, well-tolerated medicine for prophylactic treatment of migraine, and still have prophylactic effect after medicine discontinuation. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02035111; Data of registration: 2014-01-10.

Menstrual blood derived mesenchymal stem cells combined with Bushen Tiaochong recipe improved chemotherapy-induced premature ovarian failure in mice by inhibiting GADD45b expression in the cell cycle pathway.

BACKGROUND: To investigate the therapeutic effects of menstrual blood derived mesenchymal stem cells (MB-MSCs) combined with Bushen Tiaochong recipe (BSTCR) on epirubicin induced premature ovarian failure (POF) in mice. METHODS: Twenty-four female C57BL/6 mice of 6-8 weeks were intraperitoneally injected with epirubicin to induce POF, and then they were randomized into 4 groups of 6 mice each and treated with PBS, MB-MSCs, BSTCR, and MB-MSCs combined with BSTCR, respectively. Six mice of the same age were used as controls. Vaginal smear, TUNEL and hematoxylin-eosin staining were to observe estrous cycles, ovarian cell apoptosis and follicles. Enzyme-linked immunosorbent analysis determined serum estradiol, follicle-stimulating hormone (FSH) and anti-Müllerian hormone (AMH) levels. RT-qPCR and Western Blot analysis were to determine GADD45b, CyclinB1, CDC2 and pCDC2 expressions. RESULTS: Epirubicin treatment resulted in a decrease in the number of primordial, primary, secondary and antral follicles, an increase in the number of atretic follicles and ovarian cell apoptosis, a decrease in estradiol and AMH levels, an increase in FSH levels, and estrous cycle arrest. However, MB-MSCs combined with BSTCR rescued epirubicin induced POF through down-regulating GADD45b and pCDC2 expressions, and up-regulating CyclinB1 and CDC2 expressions. The combined treatment showed better therapeutic efficacy than BSTCR or MB-MSCs alone. CONCLUSIONS: MB-MSCs combined with BSTCR improved the ovarian function of epirubicin induced POF mice, which might be related to the inhibition of GADD45b expression and the promotion of CyclinB1 and CDC2 expressions. The combined treatment had better therapeutic efficacy than BSTCR or MB-MSCs alone.

Anti-N-methyl-D-aspartate receptor encephalitis mimics neuroleptic malignant syndrome: case report and literature review.

BACKGROUND: Anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis is a severe autoimmune disease characterized by complicated psychiatric and neurological symptoms and a difficult diagnosis. This disorder is commonly misdiagnosed, and diagnosis is often delayed. The clinical signs can mimic other psychiatric abnormalities, such as neuroleptic malignant syndrome (NMS) that is usually caused by antipsychotic exposure. This fact raises the question of whether the symptoms common to NMS are due to anti-NMDA receptor encephalitis or established NMS. CASES PRESENTATION: We describe a rare case of a 29-year-old male without psychiatric history who initially presented with a fever, altered consciousness, behavioral changes, rigidity, and elevated creatine kinase. He was initially diagnosed with NMS. NMS-like symptoms did not improve with active treatments and disappeared for a long period after discontinuing antipsychotics. The patient gradually developed a complicated disease progression, including speech impairment, mutism, and movement disorders, and symptom progression led to the final diagnosis of anti-NMDA receptor encephalitis. The related pathophysiological mechanisms, clinical features, and treatment of this disease are reviewed. CONCLUSION: We highlight that the natural progress of anti-NMDA receptor encephalitis can mimic the symptoms of NMS and NMS-like features could be due to anti-NMDA receptor encephalitis upon antipsychotic exposure, and not true NMS. Clinically, the suspicion of NMS may serve as a significant alarm to suspect anti-NMDA receptor encephalitis and lead neurologists or psychiatrists to investigate such a diagnosis.

Multimorbidity and Health-Related Quality of Life in Old Age: Role of Functional Dependence and Depressive Symptoms.

OBJECTIVES: To examine the associations of multimorbidity patterns with health-related quality of life (HRQL) in rural-dwelling older adults in China, and to explore to what extent their associations were mediated by functional dependence and depressive symptoms. DESIGN: Population-based cross-sectional study. SETTING AND PARTICIPANTS: 1497 participants (age ≥60 years; 66.4% women) in the 2014-2016 examination of the Confucius Hometown Aging Project who were living in a rural community near Qufu, Shandong, China. MEASURES: Data on demographics, lifestyles, chronic health conditions, and use of medications were collected through interviews, clinical examinations, and laboratory tests. Multimorbidity was defined as co-occurrence of ≥2 chronic diseases in the same person. The 15-item Geriatric Depression Scale (GDS-15) was used to assess depressive symptoms, and EQ-5D-3L was used to assess HRQL. RESULTS: Multimorbidity was present in 83.8% of the participants (women vs men: 85.5% vs 80.6%, P = .015). Exploratory factor analysis identified 4 patterns of multimorbidity, that is, patterns of cardiovascular-degenerative, respiratory, neurologic-thyroid, and metabolic-cognitive-cerebrovascular diseases. The neurologic-thyroid disease pattern did not show a significant association with HRQL. The 3 other patterns were associated with poor HRQL and had a diverse impact on different dimensions of HRQL. Mediation analysis suggested that functional dependence and the presence of depressive symptoms could mediate 24.8% and 21.8%, respectively, of the association between the number of chronic diseases and poor HRQL. CONCLUSIONS/IMPLICATIONS: Multimorbidity is associated with poor HRQL in older adults, in which functional dependence and depressive symptoms partly mediate their associations. Prevention and proper management of dependence and depressive symptoms in older people with multimorbidity may help maintain and improve quality of life.

Endometrial mesenchymal stem cells isolated from menstrual blood repaired epirubicin-induced damage to human ovarian granulosa cells by inhibiting the expression of Gadd45b in cell cycle pathway.

BACKGROUND: To explore the effect of mesenchymal stem cells isolated from menstrual blood (MB-MSCs) on epirubicin-induced damage to human ovarian granulosa cells (GCs) and its potential mechanisms. METHODS: The estradiol, progesterone, anti-Müllerian hormone, inhibin A, and inhibin B levels were determined using enzyme-linked immunosorbent assay. The proliferation of GCs was detected by Cell Counting Kit-8 assays. The cell cycle distribution was detected by propidiumiodide single staining. The apoptosis of GCs was determined using Annexin V and 7-AAD double staining. The differentially expressed genes of GCs were analyzed with Affymetrix Human Transcriptome Array 2.0 gene chip and verified with Western blot analysis. RESULTS: Epirubicin inhibited the secretion of estradiol, progesterone, anti-Müllerian hormone, inhibin A, and inhibin B and the proliferation of GCs; arrested these GCs in G2/M phase; and promoted the apoptosis of GCs. However, MB-MSCs repaired epirubicin-induced damage to GCs. Differentially expressed genes of GCs, Gadd45b, CyclinB1, and CDC2, were found by microarray and bioinformatics analysis. Western blot showed that epirubicin upregulated Gadd45b protein expression and downregulated CyclinB1 and CDC2 protein expression, while MB-MSCs downregulated Gadd45b protein expression and upregulated CyclinB1 and CDC2 protein expression. CONCLUSIONS: MB-MSCs repaired epirubicin-induced damage to GCs, which might be related to the inhibition of Gadd45b protein expression.