Association between Anatomical Variations of the Circle of Willis and Covert Vascular Brain Injury in the General Population.

BACKGROUND AND PURPOSE: The circle of Willis (COW) is a circulatory anastomosis located at the base of the brain. Little is known about the association between covert vascular brain injury and COW configurations in the general population. We explored this relationship in a community-based Chinese sample. METHODS: A total of 1,055 patients (mean age, 54.8 ± 8.9 years; 36.0% men) without intracranial arterial stenosis were included in the analysis. Magnetic resonance imaging was performed to evaluate the presence of imaging markers of covert vascular brain injury, including white matter hyperintensities (WMHs), lacunes, cerebral microbleeds (CMBs), enlarged perivascular spaces, and brain atrophy. Magnetic resonance angiography was used to classify the COW configurations according to the completeness, symmetry, and presence of the fetal posterior cerebral artery (FTP). The association between vascular lesions and variations in COW was analyzed. RESULTS: Among the 1,055 patients, 104 (9.9%) had a complete COW. Completeness correlated with age (p = 0.001). Incomplete COW was positively associated with WMH severity (OR = 2.071; 95% CI, 1.004-4.270) and CMB presence (OR = 1.542; 95% CI, 1.012-2.348), independent of age and sex. The presence of FTP was associated with lacunes (OR = 1.878; 95% CI, 1.069-3.298), more severe WMHs (OR = 1.739; 95% CI, 1.064-2.842), and less severe enlarged perivascular spaces (OR = 0.562; 95% CI, 0.346-0.915). CONCLUSIONS: COW configuration was significantly related to various covert vascular brain injuries.

Neurophobia among medical students and resident trainees in a tertiary comprehensive hospital in China.

BACKGROUND: Medical students and residents have been revealed to have extraordinary difficulties in managing patients with neurological complaints. However, specific information on Chinese trainees is scarce. Herein, we aimed to uncover the presence of, contributing factors for, and potential solutions to neurophobia among medical students and resident trainees in China. METHODS: Questionnaires were administered to the medical students of Peking Union Medical College and residents of the Internal Medicine Residency Training Program at Peking Union Medical College Hospital. We asked about perceived difficulty, knowledge, interest, and confidence in neurology in contrast to six other specialties. The reasons why neurology is regarded as difficult and approaches for improving neurological teaching have been appraised. RESULTS: A total of 351 surveys were completed by 218 medical students and 133 residents. The response rate exceeded 70% in both groups. The prevalence of neurophobia was 66.1% and 58.6% among medical students and residents, respectively. Respondents declared that greater difficulty was observed in neurology than in other specialties, and the management of patients with neurological problems was the least comfortable (p < 0.0001). Neurophobia has various perceived causes, and neuroanatomy is regarded as the most important contributor. Nearly 80% of medical students felt that improvements in neurology teaching could be achieved through further integration of preclinical and clinical neurological teaching. CONCLUSIONS: The findings of the first survey on neurophobia in China are in accordance with those of previous studies. Neurophobia is highly prevalent in Chinese medical students and residents. Strategies to improve teaching, including enhanced integration of teaching and more online resources, are needed to prevent neurophobia.

[Quality evaluation of Commelina communis from different origins based on multicomponent content determination combined with chemometrics].

This research established a high-performance liquid chromatography(HPLC) method for simultaneous determination of isoorientin, orientin, vitexin, and isovitexin in Commelina communis to conduct content difference analysis and quality evaluation of 62 batches of C. communis from different origins. The HPLC content determination was performed on a Dikma Platisil ODS chromatographic column(4.6 mm×250 mm, 5 µm), with acetonitrile-0.1% formic acid(14∶86) as the mobile phase. The detection wavelength was set at 348 nm, the flow rate was 1.0 mL·min~(-1), and the column temperature was 35 ℃. The differences in origins and quality of 62 batches of C. communis were studied by chemometrics. The results showed that the determination of four components mani-fested a good linear relationship in the range of mass concentration(r>0.999 9), and the average recovery rate was 96.17%-103.0%. The relative standard deviations(RSDs) of precision, stability, and repeatability were all less than 2.0%. The content of four components from high to low was isoorientin>isovitexin>orientin>vitexin. Forty-seven batches of C. communis with clear origins were classified into six categories by chemometrics. C. communis from different origins had different qualities. Generally, C. communis from Western China, Central China, and South of China had superior qualities. The HPLC method established in this study is specific, simple, and efficient, which provides references for the comprehensive evaluation of the quality of C. communis. The chemometrics shows that the qualities of C. communis from different origins are largely different. Isoorientin can be used as an index to determine the content of C. communis, and its content limit should be set no less than 0.023%.

Inhibition of TRIM32 by ibr-7 treatment sensitizes pancreatic cancer cells to gemcitabine via mTOR/p70S6K pathway.

Pancreatic cancer is one of the most notorious diseases for being asymptomatic at early stage and high mortality rate thereafter. However, either chemotherapy or targeted therapy has rarely achieved success in recent clinical trials for pancreatic cancer. Novel therapeutic regimens or agents are urgently in need. Ibr-7 is a novel derivative of ibrutinib, displaying superior antitumour activity in pancreatic cancer cells than ibrutinib. In vitro studies showed that ibr-7 greatly inhibited the proliferation of BxPC-3, SW1990, CFPAC-1 and AsPC-1 cells via the induction of mitochondrial-mediated apoptosis and substantial suppression of mTOR/p70S6K pathway. Moreover, ibr-7 was able to sensitize pancreatic cancer cells to gemcitabine through the efficient repression of TRIM32, which was positively correlated with the proliferation and invasiveness of pancreatic cancer cells. Additionally, knockdown of TRIM32 diminished mTOR/p70S6K activity in pancreatic cancer cells, indicating a positive feedback loop between TRIM32 and mTOR/p70S6K pathway. To conclude, this work preliminarily explored the role of TRIM32 in the malignant properties of pancreatic cancer cells and evaluated the possibility of targeting TRIM32 to enhance effectiveness of gemcitabine, thereby providing a novel therapeutic target for pancreatic cancer.

Different Types of Circulatory Inflammatory Biomarkers Associated with Cerebral Arterial Atherosclerosis and Dolichoectasia.

BACKGROUND: Although inflammation is found to be related to arteriopathy pathogenesis, it is yet to be determined the distinct correlations of specific inflammatory biomarker types contributing to different cerebral large vessel diseases. We aimed to investigate the association between multiple inflammatory biomarkers and cerebral atherosclerosis and dolichoectasia in a community-based sample. METHODS: A total of 960 participants of the Shunyi study were included. A panel of 14 circulatory inflammatory biomarkers was assessed and then grouped in three sets as systemic, endothelial-related, and media-related inflammation, based on underlying different inflammatory cascades. Intracranial atherosclerotic stenosis (ICAS), dolichoectasia estimated by magnetic resonance angiography, and carotid plaques estimated by ultrasound were also performed. RESULTS: Endothelial-related inflammatory group was related to the presence of ICAS (R2 = 0.215, p = 0.024) and carotid plaques (R2 = 0.342, p = 0.013). Backward stepwise elimination showed that E-selectin was prominent (ß = 0.67, 95% CI: 0.54-0.85, p = 0.001; ß = 0.79, 95% CI: 0.68-0.93, p = 0.005). Systemic inflammatory group was associated with an increased basilar artery diameter (R2 = 0.051, p < 0.001), and backward stepwise elimination showed that IL-6 was prominent (ß = 0.07, 95% CI: 0.03-0.11, p < 0.001). CONCLUSION: Different types of inflammatory biomarkers were associated with atherosclerosis and dolichoectasia, respectively, implying dissimilar inflammatory processes. Further confirming of their distinct anti-inflammatory roles as potential therapeutic targets is warrant.

Rare NOTCH3 Variants in a Chinese Population-Based Cohort and Its Relationship With Cerebral Small Vessel Disease.

BACKGROUND AND PURPOSE: Researches on rare variants of NOTCH3 in the general Chinese population are lacking. This study aims to describe the spectrum of rare NOTCH3 variants by whole-exome sequencing in a Chinese community-based cohort and to investigate the association between rare NOTCH3 variants and age-related cerebral small vessel disease. METHODS: The cross-sectional study comprised 1065 participants who underwent whole-exome sequencing and brain magnetic resonance imaging. NOTCH3 variants with minor allele frequency<1% in all 4 public population databases (1000 Genomes, ESP6500siv2_ALL, GnomAD_ALL, and GnomAD_EAS) were defined as rare variants. Multivariable linear and logistic regressions were used to investigate the associations between rare NOTCH3 variants and volume of white matter hyperintensities and cerebral small vessel disease burden. Clinical and imaging characteristics of rare NOTCH3 variant carriers were summarized. RESULTS: Sixty-five rare NOTCH3 variants were identified in 147 of 1065 (13.8%) participants, including 57 missense single nucleotide polymorphisms (SNPs), 5 SNPs in splice branching sites, and 3 frameshift deletions. A significantly higher volume of white matter hyperintensities and heavier burden of cerebral small vessel disease was found in carriers of rare NOTCH3 EGFr (epidermal growth factor-like repeats)-involving variants, but not in carriers of EGFr-sparing variants. The carrying rate of rare EGFr-involving NOTCH3 variants in participants with dementia or stroke was significantly higher than those without dementia or stroke (12.4% versus 6.6%, P=0.041). Magnetic resonance imaging signs suggestive of CADASIL were found in 3.4% (5/145) rare EGFr cysteine-sparing NOTCH3 variant carriers but not in 2 cysteine-altering NOTCH3 variant carriers. CONCLUSIONS: Carriers of rare NOTCH3 variants involving the EGFr domain may be genetically predisposed to age-related cerebral small vessel disease in the general Chinese population.

Clinical Features of CVT in Women and Effect on Subsequent Pregnancy: A Follow-Up Study in a Chinese National Comprehensive Hospital.

BACKGROUND AND OBJECTIVE: Cerebral venous thrombosis (CVT) is not rare in women of childbearing age. Chinese couples have been encouraged to have two children by the new family-planning policy. Concerns have been raised about the effect of CVT on subsequent pregnancies, but few studies have focused on the Chinese population. We aimed to analyze the clinical features of Chinese female CVT patients of childbearing age and study the outcome of their subsequent pregnancies after CVT. METHODS: We retrospectively analyzed the clinical data of female patients at fertile age (15-45 years) diagnosed with CVT in our hospital between January 2009 and January 2019. Information on recurrence of venous thrombotic events as well as obstetrical outcomes of subsequent pregnancies was obtained and evaluated during follow-up. RESULTS: A total of 72 patients were enrolled, mean age at CVT onset was 29.4 ± 7.9 years. The main risk factors included autoimmune system disease (27.8%), pregnancy or puerperium (12.5%), and inherited thrombophilia (11.1%). Furthermore, 58 patients were followed up for a mean time of 63.1 ± 31.4 months and 17 new pregnancies occurred in 13 women. Among the 17 pregnancies, one CVT (5.9%) recurred in a patient with antiphospholipid syndrome. Overall, 10 (58.8%) pregnancies resulted in the birth of healthy children, including 8 full-term and 2 preterm births; 7 were terminated, including 3 (17.6%) spontaneous abortions. All patients with spontaneous abortions had antiphospholipid syndrome or Behcet's disease. CONCLUSIONS: Autoimmune system disease was the most common risk factor in Chinese female CVT patients. Recurrent pregnancy-associated CVT was infrequent in women with prior CVT, but attention should be paid during subsequent pregnancies.

Severe thoracic trauma caused left pneumonectomy complicated by right traumatic wet lung, reversed by extracorporeal membrane oxygenation support-a case report.

BACKGROUND: Double lumen intubation and one-lung ventilation should be applied without delay in cases of traumatic main bronchial rupture. In most cases, when the patients' vital signs have been stabilized, the repair can be performed. However, when one-lung ventilation is complicated by traumatic wet lung, the mortality rate is likely to be much higher. CASE PRESENTATION: In this case, the patient experienced a left main bronchial rupture, bilateral traumatic wet lung, and acute respiratory distress syndrome (ARDS) because of severe thoracic trauma. Though the patient was treated with intubation and mechanical ventilation (MV), his oxygenation was still not stable. Thus, veno-venous extracorporeal membrane oxygenation (V-V ECMO) was initiated; upon improvement of oxygenation, the patient received an exploratory thoracotomy. Unfortunately, the rupture proved to be irreparable, resulting in a total left pneumonectomy. As there was severe ARDS caused by trauma, ECMO and ultra-low tidal volume (VT) MV strategy (3 ml/kg) were utilized for lung protection post-op. ECMO was sustained up to the 10th day, and MV until the 20th day, post-operation. With the support of MV, ECMO and other comprehensive measures, the patient made a recovery. CONCLUSION: V-V ECMO and ultra-low VT MV helped this thoracic trauma patient survive the lung edema period and prevented ventilator associated pneumonia (VAP). In extreme situations, with the support of ECMO, the tidal volume may be lowered to 3 ml/kg.

[Clinical Characteristics of Autoimmune Disease with Dual Seropositive Antibodies of Leucine-rich Glioma Inactivated 1 and Contactin-associated Protein 2].

Objective To explore the clinical characteristics of autoimmune disease with dual seropositive antibodies of leucine-rich glioma inactivated 1(LGI1)and contactin-associated protein 2(Caspr2).Methods The clinical data of seven patients with dual seropositive LGI1 and Caspr2 antibodies who were admitted to the Neurology Department of Peking Union Medical College Hospital from July 2014 to December 2017 were retrospectively analyzed.Results Central,peripheral and autonomic nervous systems were all involved in the seven cases;100%(7/7)presented with insomnia,myokymia,neuropahic pain and hyperhydrosis;71%(5/7)showed memory decline or psychiatric and behavioral symptoms;57%(4/7)had urinary hesitation or constipation;and 43%(3/7)had seizure.Electromyography showed 100%(6/6) of the patients had prolonged afterdischarges following normal M waves and/or abnormal spontaneous firing.Electroencephalography revealed slow waves or basic rhythm slowing in 71%(5/7)of patients.Electrocardiography showed sinus tachycardia,axis deviation,and prolonged QT intervals in 71%(5/7)of patients.One patient died from arrhythmia before immunotherapy.One died from pulmonary infection after immunotherapy.Improvement with immunotherapy was documented in the other five cases.No relapse was noted during the 1-2-year follow-up.Conclusions Autoimmune disease with dual seropositive antibodies of LGI1 and Caspr2 can diffusely affect the central,peripheral,and autonomic nervous systems.The possibility of this disease should be considered in patients with acute and subacute onset of neuropsychiatric symptoms,especially in patients with accompanying insomnia,myokymia,and hyperhydrosis.

Intracranial Arterial Dolichoectasia and Stenosis: Risk Factors and Relation to Cerebral Small Vessel Disease.

BACKGROUND AND PURPOSE: Intracranial arterial dolichoectasia (IADE) is a poorly understood arteriopathy compared with intracranial atherosclerotic stenosis (ICAS). We aimed to investigate the risk factors of IADE and ICAS and their relationship with neuroimaging markers of cerebral small vessel disease in a population-based study. METHODS: This study comprised 1237 participants (aged 57.2±9.4 years, 37.6% men) who underwent brain magnetic resonance imaging and magnetic resonance angiography. IADE was assessed based on basilar artery dolichoectasia (diameter, height of bifurcation, and laterality of basilar artery) and dilation of basilar artery and internal carotid artery (intracranial volume-adjusted diameter ≥2 SD). ICAS was defined as any degree of stenosis in at least 1 intracranial artery. The neuroimaging markers of cerebral small vessel disease, including lacunes, white matter hyperintensities, microbleeds, dilated perivascular spaces, and brain atrophy, were evaluated. RESULTS: Basilar arterial dolichoectasia was observed in 3.6% (45/1237); intracranial arterial dilation in 5.9% (67/1142); and ICAS in 15.7% (194/1237). Older age, higher systolic blood pressure, diabetes mellitus, higher LDL-C (low-density lipoprotein cholesterol) and lower HDL-C (high-density lipoprotein cholesterol) were associated with the presence of ICAS (all P<0.001), whereas only older age was associated with IADE. ICAS was associated with lacunes (odds ratio, 2.91; 95% confidence interval, 1.96-4.34; P<0.001), increased white matter hyperintensities volume (ß±SE, 0.54±0.13; P<0.001), and brain atrophy (ß±SE, -1.16±0.21; P<0.001), whereas basilar arterial dolichoectasia was mainly associated with dilated perivascular spaces in basal ganglia (odds ratio, 2.20; 95% confidence interval, 1.20-4.02; P=0.01) and, to a lesser extent, associated with lacunes and microbleeds. CONCLUSIONS: IADE and ICAS had different risk factor profiles and associated with different imaging phenotypes of cerebral small vessel disease, suggesting different underlying mechanisms.

The consequence of cerebral small vessel disease: Linking brain atrophy to motor impairment in the elderly.

In the elderly, brain structural deficits and gait disturbances due to cerebral small vessel disease (CSVD) have been well demonstrated. The relationships among CSVD, brain atrophy, and motor impairment, however, are far from conclusive. Particularly, the effect of CSVD on subcortical nuclear atrophy, motor performance of upper extremities, and associating patterns between brain atrophy and motor impairment remains largely unknown. To address these gaps, this study recruited 770 community-dwelling subjects (35-82 years of age), including both CSVD and non-CSVD individuals. For each subject, four motor tests involving upper and lower extremities were completed. High-resolution structural MRI was applied to extract gray matter (GM) volume, white matter volume, cortical thickness, surface area, and subcortical nuclear (caudate, putamen, pallidum, and thalamus) volumes. The results showed worse motor performance of lower extremities but relatively preserved performance of upper extremities in the CSVD group. Intriguingly, there was a significant association between the worse performance of upper extremities and atrophy of whole-brain GM and pallidum in the CSVD group but not in the non-CSVD group. In addition, mediation analysis confirmed a functional CSVD-to-"brain atrophy"-to-"motor impairment" pathway, that is, a mediating role of thalamic atrophy in the CSVD effect on walking speed in the elderly, indicating that CSVD impairs walking performance through damaging the integrity of the thalamus in aging populations. These findings provide important insight into the functional consequences of CSVD and highlight the importance of evaluating upper extremities functions and exploring their brain mechanisms in CSVD populations during aging.

Critical Care Resources in Guangdong Province of China: Three Surveys from 2005 to 2015.

OBJECTIVES: Data about the critical care resources in China remain scarce. The purpose of this study was to investigate the variation and distribution of critical care resources in Guangdong province from 2005 to 2015. DESIGN: Data in regard to critical care resources were collected through questionnaires and visits every 5 years from 2005. SETTING: All hospitals in Guangdong province were screened and hospitals that provide critical care services were enrolled. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: One hundred eleven, 158, and 284 hospitals that provide critical care services were enrolled in the three consecutive surveys respectively. The number of ICUs, ICU beds, intensivists, and nurses increased to 324, 3,956, 2,470, and 7,695, respectively, by 2015. Adjusted by population, the number of ICU beds per 100,000 (100,000) population increased by 147.7% from 2005 to 2015, and the number of intensivists and nurses per 100,000 population increased by 35.3% and 55.1% from 2011 to 2015. However, the numbers in the Pearl River Delta, a richer area, were higher than those in the non-Pearl River Delta area (ICU beds: 4.64 vs 2.58; intensivists: 2.90 vs 1.61; nurses: 9.30 vs 4.71 in 2015). In terms of staff training, only 17.85% of intensivists and 14.29% of nurses have completed a formal accredited critical care training program by 2015. CONCLUSIONS: Our study was the first one to investigate the trend and distribution of critical care resources in China. The quantity of ICU beds and staff has been increasing rapidly, but professional training for staff was inadequate. The distribution of critical care resources was unbalanced. Our study can be beneficial for healthcare policymaking and the allocation of critical care resources in Guangdong province and other provinces in China.

Deacetylisovaltratum disrupts microtubule dynamics and causes G2/M-phase arrest in human gastric cancer cells in vitro.

AIM: Deacetylisovaltratum (DI) is isolated from the traditional Chinese herbal medicine Patrinia heterophylla Bunge, which exhibits anti-cancer activity. Here, we investigated the effects of DI on human gastric carcinoma cell lines in vitro and elucidated its anti-cancer mechanisms. METHODS: Human gastric carcinoma AGS and HGC-27 cell lines were treated with DI, and cell viability was detected with MTT assay. Cell cycle stages, apoptosis and mitochondrial membrane potential were measured using flow cytometry. Protein levels were analyzed by Western blotting. Tubulin polymerization assays and immunofluorescence were used to characterize the tubulin polymerization process. RESULTS: DI inhibited the cell viability of AGS and HGC-27 cells in a dose- and time-dependent manner with IC50 values of 12.0 and 28.8 µmol/L, respectively, at 24 h of treatment. Treatment with DI (10-100 µmol/L) dose-dependently promoted tubulin polymerization, and induced significant G2/M cell cycle arrest in AGS and HGC-27 cells. Moreover, DI treatment disrupted mitochondrial membrane potential and induced caspase-dependent apoptosis in AGS and HGC-27 cells. CONCLUSION: DI induces G2/M-phase arrest by disrupting tubulin polymerization in human gastric cancer cells, which highlights its potent anti-cancer activity and potential application in gastric cancer therapy.

Intracranial atherosclerosis in Chinese young adult stroke patients.

BACKGROUND: Until now, intracranial atherosclerosis has been less well studied because of its rarity. We sought to investigate the prevalence and risk factors of intracranial atherosclerosis in Chinese young adult stroke patients. METHODS: We retrospectively reviewed the medical records of consecutive young adult patients with first-ever ischemic stroke at our institution from May 2007 to May 2012. The demographic features and risk factors of intracranial large-artery atherosclerotic (LAA) stroke were analyzed by comparison with other stroke subtypes. RESULTS: One hundred ninety-seven patients (age 39±9 years, 127 male) were recruited. There were 81 (41%) patients with LAA stroke, including 68 (35%) strokes because of intracranial stenosis. Male gender (P=.001), dyslipidemia (P=.015), smoking (P<.001), hypertension (P<.001), hyperhomocysteinemia (P=.003), and family history of stroke (P=.024) were more common in patients with intracranial LAA stroke than with non-LAA stroke. A high percentage of patients with intracranial LAA stroke had multiple modifiable risk factors (ie, at least 2 of dyslipidemia, hypertension, diabetes mellitus, smoking, and hyperhomocysteinemia), much more than the patients with non-LAA stroke (82% versus 42%, P<.001). Simultaneous multiple modifiable risk factor exposure was the strongest "risk factor" for intracranial LAA stroke, with the adjusted odds ratio of 4.99. CONCLUSIONS: Intracranial atherosclerosis is highly prevalent in Chinese young stroke patients. Our results suggest that simultaneous exposure to multiple risk factors may contribute to the early development of intracranial atherosclerosis.

[Microsurgical management of male infertility in china: 15-year development and prospects].

Male infertility is a common and complex disease in urology and andrology, and for many years there has been no effective surgical treatment. With the emergence of microsurgery and assisted reproductive medicine (IVF/ICSI), rapid development has been achieved in the treatment of male infertility. The Center for Male Reproductive Medicine and Microsurgery at Weill Cornell Medical College of Cornell University has been playing an important leading role in developing microsurgical techniques for the management of male infertility. The development of microsurgical treatment of male infertility in China has experienced the 3 periods of emerging, making, and boosting ever since its systematic introduction from Weill Cornell Medical College 15 years ago. At present, many Chinese hospitals have adopted microsurgery in the management of male infertility, which has contributed to the initial establishment of a microsurgical treatment system for male infertility in China. However, some deficiencies do exist concerning microsurgical treatment of male infertility, as in normalized technical training programs for competent surgeons, unified criteria for evaluation of surgical outcomes, and detailed postoperative follow-up data. This article presents an overview on the 15-year development of microsurgical management of male infertility in China, points out the existing deficiencies, and offers some propositions for the promotion of its development.

Association of Rare NOTCH3 Variants With Prevalent and Incident Stroke and Dementia in the General Population.

BACKGROUND: It is uncertain whether rare NOTCH3 variants are associated with stroke and dementia in the general population and whether they lead to alterations in cognitive function. This study aims to determine the associations of rare NOTCH3 variants with prevalent and incident stroke and dementia, as well as cognitive function changes. METHODS AND RESULTS: In the prospective community-based Shunyi Study, a total of 1007 participants were included in the baseline analysis. For the follow-up analysis, 1007 participants were included in the stroke analysis, and 870 participants in the dementia analysis. All participants underwent baseline brain magnetic resonance imaging, carotid ultrasound, and whole exome sequencing. Rare NOTCH3 variants were defined as variants with minor allele frequency <1%. A total of 137 rare NOTCH3 carriers were enrolled in the baseline study. At baseline, rare NOTCH3 variant carriers had higher rates of stroke (8.8% versus 5.6%) and dementia (2.9% versus 0.8%) compared with noncarriers. After adjustment for associated risk factors, the epidermal growth factor-like repeats (EGFr)-involving rare NOTCH3 variants were associated with a higher risk of prevalent stroke (odds ratio [OR], 2.697 [95% CI, 1.266-5.745]; P=0.040) and dementia (OR, 8.498 [95% CI, 1.727-41.812]; P=0.032). After 5 years of follow-up, we did not find that the rare NOTCH3 variants increased the risk of incident stroke and dementia. There was no statistical difference in the change in longitudinal cognitive scale scores. CONCLUSIONS: Rare NOTCH3 EGFr-involving variants are genetic risk factors for stroke and dementia in the general Chinese population.

Dynamic Mechanism of Cerebral Venous Disruption: Longitudinal Evidence From a Community-Based Cohort.

BACKGROUND: This study aims to investigate the temporal and spatial patterns of structural brain injury related to deep medullary veins (DMVs) damage. METHODS AND RESULTS: This is a longitudinal analysis of the population-based Shunyi cohort study. Baseline DMVs numbers were identified on susceptibility-weighted imaging. We assessed vertex-wise cortex maps and diffusion maps at both baseline and follow-up using FSL software and the longitudinal FreeSurfer analysis suite. We performed statistical analysis of global measurements and voxel/vertex-wise analysis to explore the relationship between DMVs number and brain structural measurements. A total of 977 participants were included in the baseline, of whom 544 completed the follow-up magnetic resonance imaging (age 54.97±7.83 years, 32% men, mean interval 5.56±0.47 years). A lower number of DMVs was associated with a faster disruption of white matter microstructural integrity, presented by increased mean diffusivity and radial diffusion (ß=0.0001 and SE=0.0001 for both, P=0.04 and 0.03, respectively), in extensive deep white matter (threshold-free cluster enhancement P<0.05, adjusted for age and sex). Of particular interest, we found a bidirectional trend association between DMVs number and change in brain volumes. Specifically, participants with mild DMVs disruption showed greater cortical enlargement, whereas those with severe disruption exhibited more significant brain atrophy, primarily involving clusters in the frontal and parietal lobes (multiple comparison corrected P<0.05, adjusted for age, sex, and total intracranial volume). CONCLUSIONS: Our findings posed the dynamic pattern of brain parenchymal lesions related to DMVs injury, shedding light on the interactions and chronological roles of various pathological mechanisms.

Middle cerebral artery intraplaque hemorrhage: prevalence and clinical relevance.

OBJECTIVE: Little is known about the composition of middle cerebral artery (MCA) plaques and how they relate to clinical status. Using high-resolution magnetic resonance imaging (HR-MRI), we aimed to examine the occurrence of high signal on T1-weighted fat-suppressed images (HST1) of MCA plaques, which are highly suggestive of fresh or recent intraplaque hemorrhage. METHODS: We retrospectively analyzed the HR-MRI and clinical data of 107 adult patients with high-grade (>70%) MCA stenosis. On HR-MRI, HST1 within an MCA plaque was defined as an area with an intensity >150% of the signal of adjacent muscles. The relationship between HST1 and clinical presentations was analyzed. RESULTS: A total of 109 stenotic MCAs (46 symptomatic and 63 asymptomatic) on 981 image slices were analyzed. HST1 was revealed on HR-MRI in 11 vessels (10.1%, 9 symptomatic and 2 asymptomatic). The occurrence rate of HST1 between symptomatic and asymptomatic MCAs was significantly different (19.6% vs 3.2%, p = 0.01). INTERPRETATION: HST1 within MCA plaque on HR-MRI is associated with ipsilateral stroke. Our results provide new insight into the vascular biology of MCA atherosclerosis.

Factors that affect sleep quality: perceptions made by patients in the intensive care unit after thoracic surgery.

OBJECTIVE: This study identifies factors affecting sleep patterns among thoracic surgery patients in the intensive care unit (ICU) and compares the perceptions of sleep-disturbing factors between nurses and patients. METHODS: One hundred and fifty-two patients and 40 nurses were surveyed using the Pittsburgh Sleep Quality Index (PSQI) and self-designed questionnaires (for patients and nurses). All statistical analyses were carried out by SPSS, and the following statistical methods were used to evaluate the data: chi-squared test and logistic regression. RESULTS: Of 152 patients, 46.1 % reported poor sleep quality during their hospitalization; their PSQI total score was 6.95 ± 3.713. Of these, 69.1 % indicated that their sleep quality was poorer than before; 50.0 % of them changed their sleep patterns. Significant discrepancies exist between nurses and patients in the perceptions of sleep-disturbing factors of patients. CONCLUSION: Thoracic surgical patients' perceptions of their sleep in the ICU indicate poor sleep quality, which is decided by a variety of disturbing factors. Perceptions of these factors varied greatly between surveyed patients and nurses.