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Yong-Lin Liu,1 Wei-Min Xiao,1 Man-Qiu Liang,2 Zhi-Qiang Wu,1 Ya-Zhi Wang,1 Jian-Feng Qu,1 Yang-Kun Chen11Department of Neurology, Affiliated Dongguan People’s Hospital, Southern Medical University (Dongguan People’s Hospital), Dongguan, Guangdong Province, People’s Republic of China; 2Department of Radiology, Affiliated Dongguan People’s Hospital, Southern Medical University (Dongguan People’s Hospital), Dongguan, Guangdong Province, People’s Republic of ChinaCorrespondence: Yang-Kun ChenDepartment of Neurology, Affiliated Dongguan People’s Hospital, Southern Medical University (Dongguan People’s Hospital), 3 South Wandao Road, Wanjiang District, Dongguan City, Guangdong Province 523059, People’s Republic of ChinaTel +86 7 692 863 6830Fax +86 07 692 222 2353Email cykun78@163.comPurpose: Wernicke’s encephalopathy (WE) is a severe neurological disorder caused by thiamine deficiency. The most common cause of WE is alcoholism. However, there is a significant paucity of information in the existing literature relating to nonalcoholic WE. In this study, we investigated the clinical characteristics and neuroimaging findings of nine patients with nonalcoholic WE.Patients and methods: We retrospectively collated clinical data from nine patients who had been diagnosed with WE in accordance with established criteria including age, gender, risk factors and clinical manifestations. We also collated initial hematological and neuroimaging findings.Results: The mean age of the nine patients was 54.0±17.1 years; four of these patients (44.4%) were male. All nine patients had a history of fasting (range, 5–47 days) prior to WE. Four of the nine patients (44.4%) exhibited the classical triad, and eight (88.9%) showed alterations in mental status. Magnetic resonance imaging (MRI) scans showed that all nine patients had symmetric lesions of the medial thalamus. MRI also revealed other WE-related lesions in mammillary bodies (22.2%), the periaqueductal region (55.6%), the tectal plate of the midbrain (77.8%), cranial nerve nuclei (77.8%) and in the symmetric subcortical white matter (11.1%).Conclusion: Our analysis showed that fasting is a common cause of WE in nonalcoholic patients and that MRI is a useful tool for the diagnosis of WE. The most common MRI findings were symmetrical lesions of the medial thalamus lesions, followed by the tectal plate of the midbrain and cranial nerve nuclei.Keywords: Wernicke’s encephalopathy, altered mental status, magnetic resonance imaging, fasting, thiamine, alcoholism

Genomic data is growing exponentially, posing new challenges for sequence analysis and classification, particularly for managing and understanding harmful new viruses that may later cause pandemics. Recent genome sequence classification models yield promising performance. However, the majority of them do not consider the sequential arrangement of nucleotides and amino acids, a critical aspect for uncovering their inherent structure and function. To overcome this, we introduce GenoAnaCla, a novel approach for analyzing and classifying genome sequences, based on sequential pattern mining (SPM). The proposed approach first constructs and preprocesses datasets comprising RNA virus genome sequences in three formats: nucleotide, coding region, and protein. Then, to capture sequential features for the analysis and classification of viruses, GenoAnaCla extracts frequent sequential patterns and rules in three forms and in codons. Eight classifiers are utilized, and their effectiveness is assessed by employing a variety of evaluation metrics. A performance comparison demonstrates that the suggested approach surpasses the current state-of-the-art genome sequence classification and detection techniques with a 3.18% performance increase in accuracy on average., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The underlying functional alterations of brain structural changes among patients with empathy impairment following stroke remain unclear. We sought to investigate functional connectivity changes informed by brain structural abnormalities in multimodal magnetic resonance imaging (MRI) among patients with empathy impairment following stroke., Methods: We enrolled people who had experienced their first ischemic stroke, along with healthy controls. We assessed empathy 3 months after stroke using the Chinese version of the Empathy Quotient (EQ). During the acute phase, all patients underwent basic magnetic resonance imaging (MRI), followed by multimodal MRI during follow-up. Our MRI analyses encompassed acute infarction segmentation, volumetric brain measurements, regional quantification of diffusion parameters, and both region-of-interest-based and seed-based functional connectivity assessments. We grouped patients based on the severity of their empathy impairment for comparative analysis., Results: We included 84 patients who had stroke and 22 healthy controls. Patients had lower EQ scores than controls. Patients with low empathy had larger left cortical infarcts (odds ratio [OR] 4.082, 95% confidence interval [CI] 1.183-14.088), more pronounced atrophy in the right cingulate cortex (OR 1.248, 95% CI 1.038-1.502), and lower scores on the Montreal Cognitive Assessment (OR 0.873, 95% CI 0.74-0.947). In addition, the cingulate cortex served as the seed in the seed-based analysis, which showed heightened functional connectivity between the anterior cingulate gyrus and the right superior parietal lobule, specifically in the low-empathy group., Limitations: We did not evaluate the relationship between specific network involvement and empathy impairment among patients following stroke., Conclusion: Among patients with subacute ischemic stroke, reduced empathy was strongly associated with a more severe cognitive profile and atrophy of the right cingulate cortex. Our subsequent structural-informed functional MRI analysis suggests that the enhanced connectivity between the anterior cingulate gyrus and the superior parietal lobule may function as a compensatory mechanism for this atrophy., Competing Interests: Competing interests:: Yi-Shan Luo is employed by BrainNow Medical Technology Limited. Lin Shi is the director of BrainNow Medical Technology. No other competing interests were declared., (© 2024 CMA Impact Inc. or its licensors.)

Background: The non-ketotic hyperglycemic chorea (NKHC) was a rare complication for patients with diabetes mellitus, but not been well studied. In the present research, we aimed to investigate the clinical and imaging characteristics of NKHC and explore the potential association., Methods: We performed a case-control study with patients diagnosed as NKHC. The patients with group of NKHC were retrospectively recruited, while the matched group were set to screened patients with diabetes mellitus but no NKHC at a 1:3 ratio. The clinical and imaging data were collected for all the participants of the two groups. Firstly, Correlation analysis was conducted to test the difference of all the variables between the NKHC group and matched group. Then, the putative associated factors for NKHC were further identified., Results: Eleven men and 9 women with NKHC and 60 matched participants were analyzed. The mean age of the NKHC group was 68.5 ± 14.9 years. Participants with NKHC were more likely to have a higher glycosylated hemoglobin (HbA1c) level (13 ± 2.82 vs. 10.57 ± 2.71, P <0.001), and a higher frequency of renal dysfunction (estimated glomerular filtration rates <60 ml/min/1.73m 2 ) (55% vs. 20%, P =0.005). Logistic regression analyses showed that both higher HbA1c and renal dysfunction were significantly correlated with NKHC., Conclusion: A higher value of HbA1c and renal dysfunction may be associated with the occurrence of NKHC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liang, Lu, Qu and Chen.)

Background: Changes in social behavior can occur after ischemic stroke. We aimed to investigate the potential correlations between neuroimaging variables and changes in social behavior in patients who experienced subacute ischemic stroke., Methods: We prospectively screened patients with first-ever ischemic stroke. Three months after the index stroke, changes in patients' social behavior were investigated by the Frontal Behavioral Inventory (FBI), which consists of both deficit and positive groups of behaviors. The protocol of brain magnetic resonance imaging (MRI) including the baseline MRI at the acute stage and additional MRI with three-dimensional T1-weighted imaging on follow-up. Using these MRI scans, we assessed the acute infarction and the volumes of various brain structures by an automatic volumetry tool., Results: Eighty patients were enrolled. In univariate analyses, patients with deficit behavioral changes had more left cortical infarction ( r  = 0.271, p  = 0.015), Cholinergic Pathways Hyperintensities Scale scores ( r  = 0.227, p  = 0.042), DWMH volumes ( r  = 0.349, p  = 0.001), and modified Rankin Scale (mRS) scores ( r  = 0.392, p  < 0.001). Patients with positive behavioral changes had more frequency of men ( r  = 0.229, p  = 0.041) and a history of hypertension ( r  = 0.245, p  = 0.028). In multiple stepwise linear regression models, after adjusting for age, deep WMH volumes ( β  = 0.849, 95% confidence interval = 0.352-1.346, p  = 0.001) and mRS scores on follow-up ( β  = 1.821, 95% confidence interval = 0.881-2.76, p  < 0.001) were significantly correlated with deficit behavioral changes ( R 2  = 0.245)., Conclusion: Larger deep WMH volumes and poorer mRS scores on follow-up were significantly correlated with deficit behavioral changes in patients with subacute ischemic stroke., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Qu, Hu, Liu, Zhou, Cheng, Shi, Luo, Zhao and Chen.)

Background and Purpose: Panaxynol (PNN) is a common natural minor component in Umbelliferae plants. Many clinical studies have shown that PNN exhibits nutritional value and anti-inflammatory and other pharmacological activities. However, whether PNN can mediate cardiac ischemia/reperfusion injury (IRI) remains unclear. Here, we aimed to determine the potential effects of PNN on myocardial IRI., Methods: Myocardial IRI was stimulated in a mouse IRI model, and neonatal rat ventricle myocytes (NRVMs) were exposed to hypoxia/reoxygenation to construct in an vitro model. Myocardial infarction size, myocardial tissue injury, myocardial apoptotic index, hemodynamic monitoring, pyroptosis-related proteins, cardiac enzyme activities and inflammatory responses were examined to assess myocardial injury., Results: It was found that PNN administration markedly reduced myocardial infarct size and apoptosis, suppressed myocardial damage and cell pyroptosis, attenuated pro-inflammatory cytokines and neutrophil infiltration via NLRP3 inhibitor. More importantly, PNN treatment remarkably decreased the expression of TLR4/NF-κB pathway-associated proteins and NLRP3-related pyroptosis proteins by HMGB1 inhibitor. PNN also enhanced cell viability, reduced cardiac enzyme activities, suppressed apoptosis and attenuated inflammation in the isolated NRVMs. Furthermore, vitro studies indicated that MCC950 (a NLRP3 inhibitor) increased the anti-inflammatory and anti-apoptotic effects of PNN on NRVMs via HMGB1/TLR4 pathway., Conclusion: To sum up, our results demonstrate that PNN exhibits a cardioprotective effect by modulating heart IRI-induced apoptosis and pyroptosis via HMGB1/TLR4/NF-κB pathway, thereby inhibiting NLRP3 inflammasome stimulation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To build bridges between anti-α enolase antibody (anti-enolase 1 antibody, anti-ENO1 antibody) and common clinical and laboratory characteristics of systemic lupus erythematosus (SLE) and to analyze the role of anti-ENO1 antibody in the evaluation of SLE disease activity., Methods: The SLE patients with retinopathy and without retinopathy were enrolled in the study, as well as healthy individuals whose gender and age matched with those of the SLE patients. Serum anti-ENO1 antibodies were measured using enzyme-linked immunosorbent assay (ELISA), presenting as intra-group positive rate and arbitrary units (AU) value. Clinical and laboratory data were obtained from medical records., Results: The SLE retinopathy patients represented various fundus abnormalities. Ranked by percentage, the top three retinopathies were retinal hemorrhage (14/32, 43.75%), cotton-wool spots (8/32, 25.00%) and retinal vein occlusion (3/32, 9.38%). Among the 32 SLE retinopathy patients, 13 (40.63%) suffered from two or more fundus abnormalities. The positive rate and AU value of the SLE patients were higher than of the SLE patients without retinopathy (68.75% vs . 46.00%, P =0.043; 16.11%±10.35% vs . 12.06%±6.47%, P =0.045). Besides, the positive rate and AU value of the two SLE groups were both significantly higher than those of the healthy control group ( P < 0.001). Compared with the SLE-without-retinopathy group, the systemic lupus erythematosus disease activity index (SLEDAI)-2000 of the SLE retinopathy patients were significantly higher than those of the SLE patients without retinopathy (17.41±4.25 vs . 9.48±5.35, P < 0.001). Dividing all the SLE patients into an anti-ENO1-positive group and an anti-ENO1-negative group, we found that anti-ENO1-positive was more likely to be correlated to developing fever and positive result of urine occult blood ( P =0.011, P =0.042). Comparing with the patients with negative anti-ENO1 antibodies, the patients with positive anti-ENO1 antibodies had significantly higher erythrocyte sedimentation rate (ESR) [the median (range) was 29.50 (1.52-110.00) mg/L vs . 12.00 (4.00-101.00) mg/L, P =0.001], higher immunoglobulin G (IgG) [the median (range) was 14.30 (4.02-37.80) g/L vs . 10.46 (2.50-25.73) g/L, P =0.000 3], and higher blood platelet count (PLT) [(205.87×10 9 ±67.98×10 9 ) /L vs . (164.57×10 9 ±69.57×10 9 ) /L, P =0.008], as well as higher immunoglobulin A (IgA) [the median (range) was 2.85 (0.07-27.00) g/L vs . 2.05 (0.42-4.36) g/L, P =0.014]., Conclusion: The positive rate and AU value of anti-ENO1 antibody suggested higher SLE disease activity and they were elevated in SLE and SLE retinopathy.

Aim: To compare ultra-widefield (24×20 mm 2 ) swept-source optical coherence tomography angiography (SS-OCTA) and fluorescein angiography (FA) in the evaluation of diabetic retinopathy (DR) lesions., Methods: Forty-six eyes of 23 patients with treatment-naïve DR were included at Peking University People's Hospital from September 1, 2021, until December 31, 2021, as well as 23 age and gender matched healthy controls. Quantitative assessments of DR lesions on FA and SS-OCTA (superficial capillary plexus, SCP, 24×20 mm 2 ) were performed., Results: Area of fovea avascular zone (FAZ) was larger in DR cases than controls (0.34±0.069 mm 2 vs 0.287±0.108 mm 2 , P =0.006). In DR eyes, the mean FAZ area was 0.34±0.069 and 0.334±0.087 mm 2 on SS-OCTA and FA, respectively ( P =0.428), while the median FAZ perimeter was 2.382 (IQR, 2.201-2.59) and 2.333 (IQR, 2.138-2.6) mm on SS-OCTA and FA images ( P =0.733). There was no significant difference in the size of the non-perfusion area (NPA) between the images on SS-OCTA and FA (12.389, IQR 4.96-28.3 and 11.125, IQR 5-28.31 mm 2 , P =0.197). The median total microaneurysm (MA) count was 35 (IQR, 19-46) and 73 (IQR, 43-93) on SS-OCTA and FA ( P <0.001), respectively. No significant difference in intra-retinal microvascular abnormality (IRMA) and neovascularization (NV) count was found between the two techniques. The intraclass coefficient (ICCs) of all the parameters above indicated stable repeatability., Conclusion: Ultra-widefield SS-OCTA represents a reliable, noninvasive, and quantitative imaging technique in the assessment of microvasculature in DR, which offers a potential substitute for FA in DR evaluation., (International Journal of Ophthalmology Press.)

Purpose: To evaluate capillaries perfusion and retinal nerve fiber layer (RNFL) thickness diurnal changes of macular/optic disc regions among participants with or without obstructive sleep apnea-hypopnea (OSA) using spectral-domain optical coherence tomography angiography (OCTA)., Methods: In this study, we enrolled a cohort of 35 participants including 14 patients with mild-to-moderate OSA, 12 patients with severe OSA, and 9 healthy individuals. All participants had Berlin questionnaire filled. At 20:00 and 6:30, right before and after the polysomnography examination, a comprehensive ocular examination was conducted. The systemic and ocular clinical characteristics were collected, and OCTA scans were performed repeatedly. Blood flow and RNFL thickness parameters were then exported using built-in software and analyzed accordingly., Results: After sleep, the overall vessel density (VD) variables, especially macular and choriocapillaris VDs, were relatively comparative and stable. One exception was the RPC vessel density at the inside-disc region with a decreasing trend in the mild-to-moderate group (p=0.023). RNFL changes before and after sleep in the nasal-inferior and peripapillary region were statistically significant (p=0.003; p=0.043) among three groups. And multiple testing correction verified the significant difference in diurnal changes between the mild-to-moderate group and the control group in pairwise comparisons (p=0.006; p=0.02)., Conclusions: The changes of imperceptible blood flow and RNFL thickness overnight around optic disc areas could be observed in OSA patients. Despite physiological fluctuations, aberrant diurnal changes might be useful for identifying a decrease in micro-environmental stability associated with the development of various ocular diseases such as glaucoma. Other VD variables, especially macular and choriocapillaris VDs, are relatively stable in eyes of patients having OSA with different severity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cai, Liu, Zhou, Jin, Sun, Zhao, Han, Qu, Shi and Zhao.)

Purpose: To identify a novel corticotropin-releasing hormone (CRH) gene variant relevant in patients with central serous chorioretinopathy (CSC)., Methods: We performed a genetic study of CSC in families and sporadic cases with controls. Using whole-exome sequencing and linkage analysis, we identified a heterozygous insertion variant, Gln52insPro, in the CRH gene that cosegregated in two Chinese families with CSC. This variant was evaluated among an additional 1307 patients with CSC and 1438 ethnicity-matched control individuals from three independent Chinese cohorts., Results: The CRH variant was strongly associated with CSC in these cohorts of Chinese patients (Pmeta = 1.24 × 10-11; odds ratio, 3.01; 95% confidence interval, 2.15-4.21). The risk variant Gln52insPro decreased CRH gene expression., Conclusions: Our results implicate the hypothalamic-pituitary-adrenal stress response system in the pathogenesis of CSC and provide a novel rationale for therapeutic intervention.

Empathy has not been well studied in patients following ischemic stroke. We aimed to evaluate the relationships of multimodal neuroimaging parameters with the impairment of empathy in patients who had experienced subacute ischemic stroke. Patients who had experienced a first-event acute ischemic stroke were recruited, and we assessed their empathy using the Chinese version of the Empathy Quotient (EQ) 3 months after the index stroke. Multimodal magnetic resonance imaging (MRI) was conducted in all the participants to identify acute infarction and assess brain volumes, white matter integrity, and other preexisting abnormalities. We quantified the brain volumes of various subcortical structures, the ventricles, and cortical lobar atrophy. The microstructural integrity of the white matter was reflected in the mean fractional anisotropy (FA) and mean diffusivity (MD), and the regional mean values of FA and MD were quantified after mapping using the ICBM&#95;DTI&#95;81 Atlas. Twenty-three (56.1%) men and 18 (43.9%) women (mean age: 61.73 years, range: 41-77 years) were included. The median National Institutes of Health Stroke Scale (NIHSS) score at discharge was 1 (range: 0-4). On univariate analysis, the EQ was correlated with right cortical infarction (r = -0.39, p = 0.012), putamen volume (r = 0.382, p = 0.014), right putamen volume (r = 0.338, p = 0.031), and the FA value of the right sagittal stratum. EQ did not correlated with the MD value in any region of interest or pre-existing brain abnormalities. Multiple stepwise linear regression models were used to identify factors associated with EQ. After adjusting for age and the NIHSS score on admission, the frequency of right cortical infarcts negatively correlated with EQ (standardized β = -0.358, 95% confidence interval =-0.708 to -0.076, p = 0.016), and the putamen volume positively correlated with EQ (standardized β = 0.328, 95% confidence interval =0.044 to 0.676, p = 0.027). In conclusion, in patients who have experienced subacute ischemic stroke, right cortical infarction and a smaller putamen volume are associated with the impairment of empathy.

Aim: To investigate the clinical characteristics and genetic features of a Bietti crystalline dystrophy (BCD) proband in a Chinese family., Methods: A Chinese female diagnosed with BCD complicated by bilateral choroidal neovascularization (CNV) and her parents underwent complete ophthalmic examinations, including fundus autofluorescence (AF), fundus photography (FP), fundus fluorescein angiography (FFA), visual field testing, full-field electroretinography (ERG), optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). The sequencing of the CYP4V2 gene was performed to the whole family., Results: Bilateral tiny glittering crystal-like deposits and differing extent of atrophy of the retinal pigment epithelium (RPE) were found in the posterior pole of her fundus. The diffuse hypo-fluorescence shown on AF images and window defects shown on FFA both indicated the atrophy of the RPE and choriocapillaris. OCT showed the thinning of the RPE and choriocapillaris layer, ellipsoid zone (EZ) band defect and CNV in both eyes. OCTA images proofed bilateral type 2 CNV. The visual field test showed central and paracentral scotoma. ERG showed a slightly decreased b-wave in scotopic ERG. Gene sequencing identified three mutations of the CYP4V2 gene, c.802&#95;807del, c.810delT, and c.1388G>A. The mutation c.1388G>A was a novel substitution mutation., Conclusion: The novel mutation c.1388G>A may be a possible cause that could induce the clinical phenotype of BCD., (International Journal of Ophthalmology Press.)

Objective: To identify prognostic factors for revitrectomy in patients who underwent pars plana vitrectomy (PPV) for complications with proliferative diabetic retinopathy (PDR). Methods: This study was a retrospective case-control study. Clinical data of PDR patients (290 eyes) at Peking University People's Hospital from December 2019 to December 2020 were retrospectively collected.According to the number of operations, patients were divided into two groups: single PPV group (227 eyes) and revitrectomy PPV group (63 eyes). Follow-up will be conducted up to 6 months postoperatively. The BCVA was compared before and after PPV between the two groups, and postoperative complications of revitrectomy PPV group were analyzed. Quantitative data are presented as medians [ M ( Q 1 , Q 3 )]. Results: The age of single PPV group patients was 55.0 (47.0, 63.0), and the age of revitrectomy PPV group patients was 49.0 (38.0, 57.0). This difference was statistically significant ( P =0.027). The LogMAR visual acuity of two groups were 1.7 (1.0, 2.4) and 2.1 (1.4, 2.4) ( P =0.026) preoperative; the visual acuity of single PPV group was 0.75 (0.43, 1.00) ( P <0.001), and revitrectomy PPV group was 0.95 (0.60, 1.65) ( P <0.001) at 6 months postoperative. The visual acuity improvement of single PPV group was better than revitrectomy PPV group ( P =0.021). Age ( P =0.043, OR =0.97, 95% CI : 0.95-1.00), preoperative BCVA ( P =0.024, OR =1.82, 95% CI : 1.08-3.05), tractional retinal detachment (TRD) ( P =0.033, OR =2.16, 95% CI :1.06-4.37), silicone oil tamponade ( P =0.028, OR =0.48, 95% CI : 0.25-0.92) were prognostic factors of revitrectomy. Conclusion: Young age, low preoperative BCVA, TRD, and silicon oil tamponade were the potential prognostic factors of revitrectomy for PDR patients.

Background: Whether the circadian rhythms of blood pressure (BP) contribute to the presence of cerebral microbleeds (CMBs) remains unknown. This study aimed to assess the relationship between nocturnal BP and CMBs in hypertensive patients., Methods: This prospective case-control study recruited 51 hypertensive patients with CMBs and 51 hypertensive patients without CMBs, matched with age and gender, serving as controls. A 24-h ambulatory BP monitoring was conducted in all subjects. Differences in ambulatory BP parameters between the two groups were compared. Logistic regression analyzes were conducted to investigate the relationship between the ambulatory BP parameters and presence of CMBs., Results: Patients with CMBs had a significant higher nocturnal mean SBP and lower relative nocturnal SBP dipping rate. Two logistic models were constructed to explore the association between ABPM indices and the presence of CMBs, adjusted with history of ischemic stroke and smoking. In model 1, higher nocturnal mean SBP positively correlated with presence of CMBs [standardized β = 0.254, odds ratio (OR) = 1.029, p = .041]. In model 2, the relative nocturnal SBP dipping rate was negatively correlated with CMBs (standardized β = -.363, OR = 0.918, p = .007). Only patients with deep CMBs had significant higher nocturnal mean SBP and lower relative nocturnal SBP dipping rate in comparison with those without CMBs., Conclusions: Higher nocturnal SBP and lower relative nocturnal SBP dipping rate may be associated with CMBs in hypertensive patients., (© 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Objective: To detect the SMO mutations in odontogenic keratocyst (OKC) and to explore the mechanism behind. Methods: Patients with OKC who received treatment in the Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology,Peking University, from September 2012 to June 2017 were enrolled. OKC samples from 10 patients diagnosed as naevoid basal cell carcinoma syndrome (NBCCS)-related OKC (4 females and 6 males) and 20 patients diagnosed as sporadic OKC (7 females and 13 males) were collected. Genomic DNAs were extracted from fibrous capsules and epithelial lining respectively. SMO mutations were detected and analyzed by Sanger sequencing. Results: Three SMO mutations were found in one NBCCS-associated OKC who carrying c.2081C>G (p.P694R) mutation) and two sporadic OKC who carrying c.907C>T (p.L303F) mutation and c.1247&#95;1248delinsAA (p.G416E), respectively), among which the first two mutations were novel mutations that had not been reported before. Besides, two mutations in sporadic OKC were not paired with PTCH1 mutations. Conclusions: In addition to PTCH1 gene mutations, SMO gene mutations also exist in OKC which might be related to the development of OKC.

The aim of the present study was to determine the neuroimaging predictors of poor participation after acute ischemic stroke. A total of 443 patients who had acute ischemic stroke were assessed. At 1-year recovery, the Reintegration to Normal Living Index was used to assess participation restriction. We also assessed the Activities of Daily Living Scale and modified Rankin Scale (mRS) score. Brain MRI measurement included acute infarcts and pre-existing abnormalities such as enlarged perivascular spaces, white matter lesions, ventricular-brain ratio, and medial temporal lobe atrophy (MTLA). The study included 324 men (73.1%) and 119 women (26.9%). In the univariate analysis, patients with poor participation after 1 year were older, more likely to be men, had higher National Institutes of Health Stroke Scale (NIHSS) score on admission, with more histories of hypertension and atrial fibrillation, larger infarct volume, more severely enlarged perivascular spaces and MTLA, and more severe periventricular hyperintensities and deep white matter hyperintensities. Patients with participation restriction also had poor activities of daily living (ADL) and mRS score. Multiple logistic regression showed that, in model 1, age, male gender, NIHSS score on admission, and ADL on follow-up were significant predictors of poor participation, accounting for 60.2% of the variance. In model 2, which included both clinical and MRI variables, male gender, NIHSS score on admission, ADL on follow-up, and MTLA were significant predictors of poor participation, accounting for 61.2% of the variance. Participation restriction was common after acute ischemic stroke despite good mRS score. Male gender, stroke severity, severity of ADL on follow-up, and MTLA may be predictors of poor participation. Trial registration number ChiCTR1800016665., Competing Interests: Competing interests: None declared., (© American Federation for Medical Research 2022. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Purpose: Impairment of cortical cholinergic pathways (CCP) is an important risk factor for chronic vascular cognitive impairment. However, this phenomenon has rarely been studied in post-stroke cognitive impairment (PSCI). We investigated the relationship between PSCI and CCP lesions assessed by structural magnetic resonance imaging (MRI). Patients and methods: We prospectively enrolled 103 patients within 7 days of ischemic stroke onset. CCP was measured by the cholinergic pathways hyperintensities scale (CHIPS), which semiquantitatively grades MR lesions strategically located on the CCP identified in human brains. We also measured other MRI parameters, including the location and volumes of acute infarcts, cerebral microbleeds, medial temporal lobe atrophy, and white matter lesions. Neuropsychological assessments were performed using the 60-min modified vascular dementia battery (VDB) at 3 months after the index stroke, and PSCI was defined according to VDB as well as ADL. Results: Of all 103 patients, 69 men (67.0%) and 34 women (33.0%) with a mean age of 57.22 ± 12.95 years, 55 patients (53.4%) were judged to have PSCI at 3 months, including 43 (41.7%) patients with PSCI-no dementia and 12 (11.7%) patients with poststroke dementia. According to the VBD assessment, the most commonly impaired cognitive domain was visuomotor speed (27.2%) followed by verbal memory (25.2%). Univariate analysis showed that patients with PSCI were older; had higher informant questionnaire on cognitive decline in the elderly (IQCODE) scores; had more frequent previous stroke history and atrial fibrillation; and had higher CHIPS scores, more severe white matter lesions, and medial temporal lobe atrophy. PSCI patients also had higher depression scores at 3 months. In the multivariate regression analysis, age, IQCODE score, CHIPS score, and Hamilton depression rating scale score were independent predictors of PSCI. Ordinal regression analysis for risk factors of poor functional outcomes revealed that IQCODE scores and cognitive function status were related to mRS score at 3 months after stroke. Conclusion: In patients with early subacute ischemic stroke, the severity of lesions involving the CCP may be associated with cognitive impairment at 3 months. Clinical Trial Registration: Chinese Clinical Trial Registry, identifier: ChiCTR1800014982., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhong, Qu, Xiao, Chen, Liu, Wu, Qiu and Liang.)

Purpose: To evaluate the functional and structural outcomes of intravitreal conbercept monotherapy using a "3 + pro re nata (PRN)" regimen in treatment-naïve subjects with polypoidal choroidal vasculopathy (PCV) up to 12 months., Methods: Thirty subjects (30 eyes) with PCV participated in this interventional, retrospective study. All subjects received intravitreal injections of 0.5 mg (0.05 ml) conbercept using a "3 + PRN" regimen for 12 months. The changes in best-corrected visual acuity (BCVA) and optical coherence tomography (OCT) parameters, polyp lesion area, and regression rate were evaluated at baseline, month 3, and month 12., Results: At the study end-point, BCVA improved significantly from 52.80 ± 17.17 ETDRS letters at baseline to 62.20 ± 18.96 letters (P < 0.001), with a mean gain of 9.40 ± 14.97 letters. The central retinal thickness (CRT) significantly reduced from 454.93 ± 147.31 μm at baseline to 308.73 ± 106.80 μm (P < 0.001) at end-point, and the total macular volume (TMV) decreased from 9.51 ± 1.04 mm 3 at baseline to 8.32 ± 0.84 mm3 at end-point (P < 0.001). The mean volume of pigment epithelial detachment (PED) decreased from 0.73 ± 0.97 mm 3 at baseline to 0.48 ± 0.71 mm 3 (P < 0.05) at month 3. At month 12, the mean volume of PED was 0.57 ± 0.80 mm 3 (P > 0.05 compared to baseline). After the 3-monthly loading injections, 6 eyes (20.0%) showed complete polyp regression, whereas a total of 19 eyes (63.5%) showed complete regression at month 12. The average injections given per subject were 7.70 ± 1.81., Conclusion: Intravitreal conbercept using the "3 + PRN" regimen was effective in the treatment of PCV.

Background: Whether autonomic dysfunction contributes to cerebral small vessel disease (CSVD) remains unclear. This study aimed to explore the relationship between CSVD and blood pressure variability (BPV) and heart rate variability (HRV)., Methods: This case-control study recruited 50 patients with CSVD and 50 non-CSVD hypertensive age- and gender-matched controls. All participants completed a 24-h ambulatory electrocardiogram recording and ambulatory BP monitoring (ABPM). Differences in HRV and BPV between the two groups were examined. BPV indices assessed by ABPM included mean systolic BP (SBP), mean diastolic BP (DBP), coefficient of variation and weighted standard deviation of SBP and DBP., Results: CSVD patients had significant higher 24-h mean systolic BP (SBP), 24-h mean diastolic BP (DBP), daytime mean SBP, nocturnal mean SBP, and nocturnal mean DBP (P < .05 for all). CSVD patients had a significant lower nocturnal SBP fall rate compared with controls (median: 1.0 versus 6.2, respectively; P < .001) and were more likely to be non-dippers and reverse dippers. There were no differences in HRV variables between the two groups. Five logistic models were built to explore the correlations between BPV indices and CSVD. BPV indices were separately entered into the logistic regression models, together with hyperlipidemia, ischemic stroke history, current use of anti-hypertensive agents, and serum blood urea nitrogen. In models 1-3, 24-h mean SBP and nocturnal mean SBP and DBP were significantly correlated with CSVD (r 2  = 0.308-0.340). In model 4, the nocturnal SBP fall rate was negatively correlated with CSVD (odds ratio [OR] = 0.871, 95% confidence interval [CI] = 0.804-0.943; P = .001), with r 2  = 0.415 fitting the model. In model 5, the pattern of SBP dipping was significantly associated with CSVD, with non-dipper (OR = 8.389, 95%CI = 1.489-47.254; P = .016) and reverse dipper (OR = 27.008, 95%CI = 3.709-196.660; P = .001) having the highest risks of CSVD (r 2  = 0.413)., Conclusions: Lower nocturnal SBP fall rate is associated with CSVD. Non-dipper and reverse dipper hypertensive patients have a higher risk of CSVD., Competing Interests: Declarations of Competing Interest None., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Early neurological deterioration (END) is a common feature in patients with acute ischaemic stroke (AIS) receiving thrombolysis. This study aimed to investigate whether the presence of multiple hypointense vessels (MHVs) on susceptibility-weighted imaging (SWI) could predict END in patients with the anterior circulation AIS treated with recombinant tissue plasminogen activator (r-tPA)., Methods: This was a retrospective study focusing on AIS patients suffering from symptomatic stenosis or occlusion of the middle cerebral artery or internal carotid artery with r-tPA treatment. We collected clinical variables and initial haematological and neuroimaging findings. MHVs were measured on SWI performed after intravenous thrombosis and were defined as the presence of a greater number of veins or veins of a larger diameter with greater signal loss on SWI than those of the contralesional haemisphere. The degree of hyperintensity of MHVs was classified into four grades: none, subtle, moderate and extensive. END was defined as an increase in the National Institutes of Health Stroke Scale score by 2 points during the first 48 hours after the onset of symptoms. Multivariate logistic regressions were conducted to investigate the predictors of END., Results: The study included 61 patients (51 males and 10 females) with a mean age of 62.4±12.6 years. Thirty-five (57.4%) patients presented with MHVs: 8 (13.1%) were graded as subtle MHVs, while 23 (37.7%) and 4 (6.6%) were graded as moderate or extensive MHVs, respectively. Twenty patients (32.8%) presented with END. Logistic regression analysis showed that compared with patients without MHVs, moderate MHVs (adjusted OR 5.446, 95% CI 1.360 to 21.800; p=0.017) and extensive MHVs (adjusted OR 15.240, 95% CI 1.200 to 193.544; p=0.036) were significantly associated with END., Conclusions: MHVs might be a useful predictor of END in AIS patients with symptomatic large artery stenosis or occlusion after r-tPA treatment., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Very few studies have investigated the specific relationship between neutrophil-to-lymphocyte ratio (NLR) and the short-term outcomes of patients suffering from mild acute ischemic stroke (AIS) and receiving intravenous thrombolysis (IVT). This study aimed to investigate whether a high NLR is associated with a poor short-term outcome in patients with mild AIS after IVT., Methods: We retrospectively analyzed data that were prospectively acquired from patients with AIS treated with IVT. Mild AIS was defined as a National Institutes of Health Stroke Scale (NIHSS) score ≤ 7 on admission. The NLR was based on a blood test performed prior to IVT and was classified as 'high' when exceeding the 75th percentile. Follow-ups were performed at discharge and 3 months after onset. A poor outcome was defined as a modified Rankin scale (mRS) ≥3., Results: A total of 192 patients were included in this study. The median NLR was 3.0 (interquartile range [IQR]: 2.0-3.9). Fifty-one patients (26.6%) had a high NLR (≥3.9) on admission. Forty-one patients (21.4%) had a poor outcome at discharge, while 34 patients (17.7%) had a poor outcome at 3 months. Patients with a poor outcome at discharge, and at 3 months after onset, were more likely to have a high NLR at discharge (42.9% vs. 21.9%; p = .005) and at 3 months (44.1% vs. 22.8%; p = .011), compared with those with a better outcome. After adjustment for NIHSS score on admission, ipsilateral severe intracranial large artery occlusion, and atrial fibrillation, logistic regression analyses revealed that a high NLR was a significant predictor of poor outcome at discharge and at 3 months after onset., Conclusions: A high NLR on admission could be a useful marker for predicting poor short-term outcome in patients with mild AIS following IVT., (© 2020 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Background: Susceptibility weighted imaging (SWI) provides an approximate assessment of tissue perfusion and shows prominent hypointense cortical veins in the ischemic territory because of the increased concentration of deoxyhemoglobin. We aimed to evaluate whether asymmetrical prominent cortical vein sign (APCVS) on SWI can predict early neurological deterioration (END) in acute ischemic stroke patients with severe intracranial arterial stenosis or occlusion (SIASO)., Methods: One hundred and nine acute ischemic stroke patients with SIASO who underwent SWI were retrospectively recruited. END was defined as an increase in the National Institutes of Health Stroke Scale score ≧2 points despite standard treatment in the first 72 h after admission. The APCVS was defined as more and/or large vessels with greater signal loss than those in the opposite hemisphere on SWI., Results: Thirty out of the 109 (27.5%) patients developed END. Sixty (55.0%) patients presented with APCVS on SWI. APCVS occurred in 24 (80%) patients with END, whereas it only occurred in 36 (45.6%) patients without END (P = 0.001). Patients with APCVS were more likely to have END (40.0%, vs. 12.2%, P = 0.001) than those without END. Multivariate logistic regression indicated that APCVS (OR = 4.349, 95% C.I. = 1.580-11.970, P = 0.004) was a significant predictor of END in acute ischemic stroke patients with SIASO, adjusted for previous stroke history and acute infarct volume., Conclusions: In acute ischemic stroke patients with SIASO, the APCVS might be a useful neuroimaging marker for predicting END, which suggests the importance of evaluation of perfusion status.

Purpose: Fatigue has been recognized as a common non-motor problem in patients with Parkinson's disease (PD). The determination of the clinical correlates of fatigue in PD patients is necessary. The purpose of this study was to explore the risk factors related to the severity of fatigue in PD., Patients and Methods: In this study, 141 patients with PD were recruited. All patients were evaluated comprehensively, including motor function, fatigue severity scale (FSS), cognition and psychiatric status. Brain magnetic resonance imaging (MRI) examinations were performed to assess the severity of white matter hyperintensities, and the presence of silent lacunes, medial temporal lobe atrophy (MTLA), and global cortical atrophy (GCA). The crude associations of variables with FSS were examined using Pearson (nor-mally distributed) or Spearman correlation (categorical or non-normal distributed) analyses. Multiple linear regression analysis was performed to find the correlates of fatigue severity in PD patients., Results: In the whole sample, with FSS as the dependent variable in a linear regression model, Hamilton Depression Rating Scale (HAM-D), GCA, female sex were significant correlates of FSS, accounting for 24% of the variance of it. When subjects with depression (HAM-D ≥ 35) were excluded, HAM-D, GCA, female sex remained significant correlates of FSS, accounting for 22% of the variance of FSS. There is no correlation between white matter hyperintensities and FSS., Conclusion: GCA may be an important correlate of the fatigue severity commonly observed in PD patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: To assess whether the asymmetrical cortical vessel sign (ACVS) on susceptibility-weighted imaging (SWI) could predict 90-day poor outcomes in anterior circulation acute ischemic stroke (AIS) patients treated with recombinant tissue plasminogen activator (r-tPA)., Methods: Clinical data of consecutive patients with anterior circulation AIS treated with r-tPA were retrospectively analyzed. Clinical variables included age, sex, vascular risk factors, NIHSS score, onset to treatment time, and initial hematologic and neuroimaging findings. Follow-up was performed 90 days after onset. Poor outcome was defined as a modified Rankin scale (mRS) ≥3 at 90 days., Results: A total of 145 patients were included, 35 (24.1%) patients presented with ACVS (≥Grade 1) on SWI. Fifty-three (36.6%) patients had a poor outcome at 90 days. ACVS (≥Grade 1) occurred in 21 (39.6%) patients with poor outcome compared with 14 (15.2%) patients with favorable outcome (p = .001). Univariate analysis indicated that age, NIHSS score on admission, previous stroke, hemorrhagic transformation, severe intracranial large artery stenosis or occlusion (SILASO), and ACVS were associated with 90-day poor outcome (p < .05). Since SILASO and ACVS were highly correlated and ACVS had different grades, we used three logistic regression models. Results from the three models showed that ACVS was associated with 90-day poor outcome., Conclusions: In r-tPA-treated patients with anterior circulation AIS, ACVS might be a helpful neuroimaging predictor for poor outcome at 90 days., (© 2020 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Objective: The aim of this prospective cohort study was to determine the incidence and neuroimaging risk factors associated with Babinski sign following acute ischemic stroke, as well as its relationship with the functional outcome of patients., Methods: A total of 351 patients were enrolled in the study within 7 days of acute ischemic stroke. The Babinski sign along with other upper motor neuron signs were examined upon admission and between days 1 and 3 and days 5 and 7 after admission. Neuroimaging parameters included site and volume of infarction and white matter lesions. All patients were followed up at 3 months. Functional outcome was assessed with the Lawton Activities of Daily Living scale and modified Rankin Scale., Results: Babinski sign was observed in 115 of 351 (32.8%) patients in the acute ischemic stroke. These patients had higher National Institutes of Health Stroke Scale (NIHSS) scores at admission and higher rates of atrial fibrillation and cardioembolism; higher frequencies of frontal, temporal, and limbic lobes and basal ganglia infarcts; and larger infarct volume. Higher NIHSS score and basal ganglia infarct were significant predictors of the presence of Babinski sign. After adjusting for confounds, the presence of Babinski sign did not predict poor functional outcome., Conclusion: The incidence of Babinski sign was 32.8% in the acute ischemic stroke. Severe infarction and basal ganglia infarct were independent predictors of Babinski sign. Although Babinski sign is common in acute ischemic stroke patients, it does not predict poor functional outcome 3 months later., (© 2020 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

Background: The relationship between the neutrophil-to-lymphocyte ratio (NLR) and hemorrhagic transformation (HT) in acute ischemic stroke (AIS) treated with intravenous thrombolysis (IVT) remains unclear. This study assessed whether high NLR is associated with HT in this population., Methods: Data were prospectively collected for continuous patients with AIS treated with IVT and retrospectively analyzed. Clinical variables included age, sex, vascular risk factors, National Institutes of Health Stroke Scale (NIHSS) score, onset-to-treatment time, and initial hematologic and neuroimaging findings. HT was confirmed by imaging performed within 3 days after IVT. Symptomatic HT (sHT) was defined as NIHSS score increased by 4 points compared with that on admission according to previously published criteria. The NLR value was based on the blood examination before IVT, and high NLR was defined as ≥75th percentile., Results: The study included 285 patients (201 (70.5%) males, the mean age was 62.3 years (range 29-89)). Seventy-two (25.3%) patients presented with HT, including three (1.1%) with sHT. The median NLR was 2.700 (1.820-4.255, interquartile range). Seventy-one (24.9%) patients had a high NLR (≥4.255) on admission. Univariate analysis indicated that patients with HT had higher NIHSS scores ( P < 0.001), systolic blood pressure (SBP), platelet counts, lymphocyte counts, and NLR ( P < 0.001), systolic blood pressure (SBP), platelet counts, lymphocyte counts, and NLR ( P < 0.001), systolic blood pressure (SBP), platelet counts, lymphocyte counts, and NLR ( P < 0.001), systolic blood pressure (SBP), platelet counts, lymphocyte counts, and NLR ( P < 0.001), systolic blood pressure (SBP), platelet counts, lymphocyte counts, and NLR ( P < 0.001), systolic blood pressure (SBP), platelet counts, lymphocyte counts, and NLR ( P < 0.001), systolic blood pressure (SBP), platelet counts, lymphocyte counts, and NLR ( P < 0.001), systolic blood pressure (SBP), platelet counts, lymphocyte counts, and NLR ( P < 0.001), systolic blood pressure (SBP), platelet counts, lymphocyte counts, and NLR (., Conclusions: High NLR could be a useful marker for predicting HT in AIS patients after IVT., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Yong-Lin Liu et al.)

Background: Mineral and bone disorder (MBD) in hemodialysis patients is associated with increased morbidity and mortality. Studies on the MBD status of hemodialysis patients at high altitudes are extremely limited. Methods: A total of 146 hemodialysis patients from 5 local hospitals across all districts with hemodialysis centers in the Tibetan Plateau were enrolled in this cross-sectional study. Parameters related to MBD, including serum phosphorus (P), calcium (Ca), and intact parathyroid hormone (iPTH) levels, were measured. The achievement of MBD goals was compared with the achievement in the Dialysis Outcomes and Practice Study (DOPPS) 3, DOPPS 4 and a multicenter study of MBD in China. Factors associated with hyperphosphatemia were examined. Results: Altogether, 146 hemodialysis patients were recruited from the Tibetan Plateau. According to the K/DIGO guidelines, there were low achievement rates for serum Ca (40.4%), P (29.7%), and iPTH (47.1%). As for the (KDOQI) guidelines, the rates of achievement of defined targets were 38.4%, 33.7% and 16.4% for serum Ca, P and iPTH, respectively. The percentages of patients reaching the KDOQI targets for corrected Ca, P, and iPTH were significantly lower for Tibetan patients than the percentages found in DOPPS 3 (38.4% vs. 50.4%, 33.7% vs. 49.8%, and 16.4% vs. 31.4%, respectively, all p  < .001) and DOPPS 4 (38.4% vs. 56.0%, 33.7% vs. 54.5%, and 16.4% vs. 35.3%, respectively, all p  < .001). The percentage of patients reaching the KDOQI targets for iPTH was significantly lower in Tibet than in the plain areas of China (16.4% vs. 26.5%, p  < .001). The proportion of patients with hypocalcemia was higher in Tibet than in the plain areas (44.5% vs. 19.4%, p  < .001). The percentage of local patients with optimal P was significantly higher for patients with an activated vitamin D prescription than for patients without an activated vitamin D prescription (45.3% vs. 19.3%, p  < .001). Age and the activated vitamin D prescription were independently associated with hyperphosphatemia. Conclusion: The MBD status of hemodialysis patients in Tibet is far from the ideal level. High altitude is one of the possible causes of the differences found, but not the principal one. It is necessary for medical staff in Tibet to improve the detection and treatment of MBD.

Purpose: The aim of this study was to investigate the association between preexisting cerebral abnormalities in patients with acute ischemic stroke upon their functional outcomes., Methods: We recruited 272 patients with first-ever acute ischemic stroke. Cerebral abnormalities on magnetic resonance imaging included infarction, silent brain infarcts (SBI), enlarged perivascular spaces, white matter lesions (WMLs), global brain atrophy, and medial temporal lobe atrophy (MTLA). Functional outcomes were assessed using the instrumental activities of daily living (IADL) scale and basic activities of daily living (BADL) scale, at 3 and 6 months after the index stroke., Results: Two hundred and fifty patients completed the 3-month follow-up and 246 patients completed the 6-month follow-up. Univariate analyses showed that patients with poor IADL and BADL were older, more likely to be men, had higher National Institutes of Health Stroke Scale (NIHSS) score on admission, more frequent atrial fibrillation, and large artery atherosclerosis subtypes. They also had more frequent cortical infarcts, subcortical infarcts, infratentorial infarcts, larger infarct volume, more frequent presence of SBI, severe WMLs, and MTLA. In multiple regression analyses, NIHSS on admission, subcortical region infarct and MTLA were significant predictors of poor IADL at 3 months. National Institutes of Health Stroke Scale on admission, SBI and MTLA were significant predictors of poor IADL at 6 months. National Institutes of Health Stroke Scale on admission and MTLA were significant predictors of poor BADL at 3 months. National Institutes of Health Stroke Scale on admission and SBI were significant predictors of poor BADL at 6 months., Conclusions: In patients with acute ischemic stroke, the presence of SBI, and severe MTLA represent significant predictors of poorer functional outcomes, thus highlighting the importance of preexisting cerebral abnormalities.

Aim: To measure and analysis axial length (AL)/corneal radius of curvature (CRC) ratio and other refractive parameters, provide a medical reference range for refractive development evaluation and earlier visual impairment screening of 3 to 4y kindergarten students., Methods: Between April and June 2017, a total of 4350 participants aged 3- to 4-year-old (8700 eyes) from 10 cluster random sampling kindergartens in Shanghai, Pudong District were involved. According to the measurement and analysis of the unaided visual acuity (VA), AL, CRC, AL/CRC ratio, astigmatism and other refractive parameters, the data distribution and reference range were obtained., Results: Uncorrected VA of examined children was 0.23±0.08 (logMAR, mean±SD) [95% confidence interval (CI) range ≤0.36]; AL was 22.10±0.79 mm (95%CI 20.55-23.65); CRC was 7.86±0.26 mm (95%CI, 7.35-8.37); AL/CRC ratio was 2.81±0.12 (95%CI, 2.57-3.05). The median of astigmatism was -0.5 D, a total of 56.3% had astigmatism <-0.50 D, 85.3%<-1.00 D, 6.7%>-1.50 D; 71% were astigmatism with the rule. Eye-specific analyses were conducted. Statistical difference of VA was in right and left eyes. There were no significant differences between two eyes of AL, CRC, AL/CRC ratio and astigmatism ( P >0.05)., Conclusion: VA and AL/CRC ratio reference could be used to assess refractive development in children and screening uncorrected refractive errors or amblyopia. Astigmatism needs to be considered in the diagnosis.

Background: Anxiety is prevalent after a stroke. The pathophysiological mechanisms underlying the development of poststroke anxiety (PSA) remain unclear. The aim of this study was to investigate the clinical and neuroimaging risk factors for development of PSA and examine the effects of PSA on activities of daily living (ADL) and quality of life (QOL) in Chinese patients with ischemic stroke. Methods: Two hundred nineteen patients with acute ischemic stroke were recruited to the study. A series of comprehensive assessments, including Hamilton Anxiety Rating Scale (HARS), Hamilton Depression Rating Scale (HDRS), Lawton ADL Scale, and the Stroke-Specific Quality of Life (SSQOL) Scale, were conducted in the acute stage and 3 months after stroke. Magnetic resonance imaging assessment focused on evaluation of infarctions, white matter lesions, and brain atrophy. Results: In the acute stage and 3 months after stroke, 34 (16%) and 33 (15%) patients had PSA, respectively. Multiple logistic regression analysis indicated that HDRS (OR = 1.269, 95% CI = 1.182-1.364, P < 0.001) and acute infarcts in cerebral hemispheric white matter (CHWM; OR = 2.902, 95% CI = 1.052-8.007, P = 0.040) were significant correlates of PSA in the acute stage of stroke. Three months after stroke, these correlates remained significant predictors, along with male sex. Multiple linear regressions showed that age, NIHSS, HARS, and HDRS in the acute stage were significant predictors for both ADL and SSQOL at 3 months after stroke. Conclusion: Depressive symptoms are the major correlates of PSA while more severe PSA is associated with poorer ADL and health-related QOL. Acute lesions involving CHWM may correlate with PSA in ischemic stroke patients with mild-to-moderate neurologic deficits, supporting a lesion-location hypothesis in PSA.

Johnson noise thermometers infer thermodynamic temperature from measurements of the thermally-induced current fluctuations that occur in all electrical conductors. This paper reviews the status of Johnson noise thermometry and its prospects for both metrological measurements and for practical applications in industry. The review begins with a brief description of the foundations and principles of Johnson noise thermometry before outlining the many different techniques and technological breakthroughs that have enabled the application of JNT to high-accuracy, cryogenic, and industrial thermometry. Finally, the future of noise thermometry is considered. As the only purely electronic approach to thermodynamic temperature measurement, Johnson noise thermometry has appeal for metrological applications at temperatures ranging from below 1 μK up to 800 K. With the rapid advances in digital technologies, there are also expectations that noise thermometry will become a practical option for some industrial applications reaching temperatures above 2000 K.

Background and Purpose- The aim of the study was to assess the effect of lesion severity in cortical cholinergic pathways in acute ischemic stroke patients on functional outcomes. Methods- The study sample consisted of 214 men (70.9%) and 88 women (29.1%) with acute ischemic stroke. We used the Cholinergic Pathways Hyperintensities Scale (CHIPS) to assess the severity of lesions in cortical cholinergic pathways using brain magnetic resonance imaging. The other magnetic resonance imaging parameters included infarction, white matter lesions, and medial temporal lobe atrophy. Functional outcome was assessed using the Lawton activities of daily living (ADL) scale at 3 and 6 months after the index stroke. We also assessed disability status using the modified Rankin Scale. Results- Univariate analysis showed that patients with poor functional outcomes were older, more likely to be men, had a higher National Institutes of Health Stroke Scale (NIHSS) score on admission, and had more frequent histories of previous stroke and infection complications. They also had significantly more frequent cortical infarcts, left subcortical infarcts, a larger infarct volume, more severe medial temporal lobe atrophy, and periventricular hyperintensities, and higher CHIPS scores. In the multiple regression analysis, model 1 showed that age and NIHSS score on admission were significant predictors of poor ADL at 3 months, with an R 2 of 45.4% fitting the model. Age, NIHSS score on admission and stroke subtype were also significant predictors of poor ADL at 6 months, with an R 2 of 37.9% fitting the model. In model 2, sex, previous stroke, NIHSS score on admission, right cortical infarcts, left subcortical infarcts and CHIPS score were significant predictors for poor ADL at 3 months, with an R 2 of 53.5%. NIHSS score on admission, stroke subtype, and CHIPS score were significant predictors for poor ADL at 6 months, with an R 2 of 40.2%. After adjustment for confounders, CHIPS score was also a significant predictor for poor modified Rankin Scale, both at 3 and 6 months. Even after removing patients with moderate-to-severe white matter lesions, higher CHIPS scores still correlated with poorer ADL and modified Rankin Scale both at both 3 and 6 months. Conclusions- In patients with acute ischemic stroke, cortical cholinergic pathways impairment is common, and the severity of lesions in the cortical cholinergic pathways may significantly predict a poorer functional outcome. Clinical Trial Registration- URL: http://www.chictr.org.cn/index.aspx . Unique identifier: ChiCTR1800014982.

Objective: China's cardiopulmonary resuscitation (CPR) training in the form of a Chinese tutor classes for the training of CPR has spread across the country. It is supported by three Chinese original theoretical systems: "2016 Chinese cardiopulmonary resuscitation expert consensus", "2018 China cardiopulmonary resuscitation training expert consensus", and "Chinese public health guidelines for cardiopulmonary resuscitation". There are five characteristics in the classes, such as the "three analysis" "three-prevention" (precaution, prewarning and early identification), "three-ways" (standardization, diversification and individuation), "three lives" (demutation, transcending and extension), "three dimensional" (time, space and society). Highlighting the Chinese CPR training of the "three training" policy for CPR training (the cultivation of a sound system, the cultivation of scientific guidelines and the cultivation of a healthy culture), the "three training" program of CPR training (training professional skills, training multidimensional and training flexible), the "three party" direction of CPR training (the application for achievement translation, the precision disseminators and theoretical innovation guides) under the new era background. A new chapter of CPR training with Chinese characteristics was composed.

Objective: To analyze the operative methods and clinical effects of autologous distal tibial cancellous bone graft with periosteum in treating cartilage injury of talus with Hepple III-IV type., Methods: From June 2014 to August 2017, 25 patients (25 feet) with Hepple III to IV cartilage injury of talus were treated with autogenous ipsilateral distal tibial cancellous bone graft. Including 14 males and 11 females, aged from 18 to 52 years with an average of (38.4±3.1) years; left foot was in 8 cases and right foot was in 17 cases. According to Hepple classification, type III of 9 cases, type IV of 16 cases. The curative effect was assessed by Amercian orthopedic foot and ankle society (AOFAS) and visual analogue scale (VAS) before operation and 12 months after operation., Results: All 25 patients were followed up for 12 to 28 months with an average of (14.2±2.5) months. AOFAS and VAS scores were improved from preoperative 53.02±10.06, 8.02±1.14 to 88.04±7.45, 1.26±1.74 at 12 months after operation ( P <0.05). According to AOFAS standard, 16 cases got excellent results, 6 good, 3 poor., Conclusions: Autologous distal tibial cancellous bone graft with periosteum is an effective method for Hepple III-IV cartilage injury of talus. It can effectively relieve ankle pain and improve ankle joint function., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© 2018 by the China Journal of Orthopaedics and Traumatology Press.)

Cerebral small vessel disease (CSVD) is a common etiology of vascular cognitive impairment with no dementia (V-CIND). Studies have revealed that cerebral microbleeds (CMBs), a feature of CSVD, contribute to cognitive impairment. However, the association between CMBs and dementia conversion in individuals with V-CIND is still unclear. Here, we analyzed the predictive role of CMBs in the conversion from V-CIND to dementia in CSVD patients. We recruited and prospectively assessed 85 patients with CSVD and V-CIND. V-CIND was evaluated using a series of comprehensive neuropsychological scales, including the Chinese version of the Montreal Cognitive Assessment and the Clinical Dementia Rating. MRI assessments were used to quantify lacunar infarcts, white matter hyperintensities, CMBs, and medial temporal lobe atrophy. Eighty-two of the 85 patients completed the assessment for dementia conversion at a 1-year follow-up assessment. Multivariate logistic regression analyses were conducted to examine independent clinical and MRI variables associated with dementia conversion. Twenty-four patients (29.3%) had converted to dementia at the 1-year follow-up, and these individuals had significantly more CMBs in the fronto-subcortical circuits. Multivariate logistic regression analyses revealed that the patients with CMBs in the fronto-subcortical circuits (odds ratio = 4.4; 95% confidence interval: 1.602-12.081, P = 0.004) and 5 or more CMBs overall (odds ratio = 17.6, 95% confidence interval: 3.23-95.84, P = 0.001) had a significantly increased risk of dementia at the 1-year follow-up. These findings indicate that CMBs in the fronto-subcortical circuits may be predictive of dementia conversion in CSVD patients with V-CIND, and thus extend the clinical significance of CMBs. This trial was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR1800017077). Protocol version: 1.0., Competing Interests: None

Objective: MicroRNAs have been found to be deregulated in lung cancers, which play crucial roles in tumorigenesis and progression. FBXW7 and FBXW11, two important F-box proteins of the ubiquitin-proteasome system (UPS), can target multiple substrates for degradation, in order to regulate cell proliferation and survival in cancers. In the present study, we aimed to explore the potential role and regulating mechanism of miR-182 in non-small cell lung cancer (NSCLC)., Methods: MiRNA expression was evaluated by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). FBXW7, FBXW11, c-Jun, c-Myc and cyclin D protein levels were detected by western blot. Cell growth was determined using cell counting kit (CCK)-8 reagent and colony formation experiment. Then, cell apoptosis and the cell cycle were analyzed on flow cytometry. The target binding activity of miR-182 with FBXW7 or FBXW11 was evaluated through the Dual-Luciferase Reporter Assay System., Results: It was confirmed that miR-182 was significantly upregulated in tumor tissues, compared with adjacent normal tissues, and this was inversely correlated to the protein levels of FBXW7 and FBXW11. The overexpression of miR-182 in NSCLC cells dramatically promoted cell growth, colony formation capacity and cell cycle progression, and inhibited apoptosis in NSCLC cells. In contrast, the downregulation of miR-182 significantly alleviated these properties in vitro . Furthermore, we demonstrated that miR-182 exerted an oncogenic role in NSCLC by directly targeting FBXW7 and FBXW11., Conclusion: These results bring new insights into the oncogenic role of miR-182 in NSCLC, indicating that miR-182 might be a novel biomarker for the diagnosis and prognosis of NSCLC., Competing Interests: None.

Aim: To assess the association between endogenous cortisol level and the risk of central serous chorioretinopathy (CSC)., Methods: Case-control studies were systematically searched on PubMed, Embase, Cochrane, China National Knowledge Infrastructure (CNKI) for publishes between January 1990 and July 2017 to assess the association between endogenous cortisol level and CSC. The main endpoints were serum cortisol level at 8 a.m. and 24-hour urine 17-hydroxysteroids level. We assessed pooled data using a random-effects model., Results: Of 86 identified studies, 5 were eligible included in our analysis. The 5 studies included a total of 315 participants, of whom 187 had CSC. Statistically significant association was observed between serum cortisol level (summary SMD=0.77, 95%CI=0.55-0.99), 24-hour urine 17-hydroxysteroids level (summary SMD=0.95, 95%CI=0.61-1.30), and the risk of CSC., Conclusion: Endogenous cortisol level is associated with an increased risk of CSC. Combined treatment targeting the serum cortisol level at 8 a.m. and 24-hour urine 17-hydroxysteroids level can be a potential preventive strategy for individuals who are at risk of CSC and therapeutic strategy for patients with CSC.

Objective: To observe the clinical effect of vacuum sealing drainage (VSD) in the treatment of complex fracture and dislocation of foot with severe soft tissue injury. Methods: From March 2012 to January 2015, a retrospective analysis of 108 cases of the foot closed complex fracture dislocation with severe soft tissue injury in Department of Foot and Ankle, the Second Hospital of Tangshan City, Tangshan.Injury mechanisms included press and crush injury, traffic accident.According to the operation the cases were divided into the VSD group (56 cases) and the control group (52 cases). The injury foot swelling after treated by open reduction and internal fixation or fusion joint fracture and dislocation. VSD technique was used to cover the wound and wound in group VSD. The wound was sutured, the sterile dressing was covered and the dressing was changed regularly in the control group. Results: Preoperative hospitalization time: 16 days in group VSD, 28 days in the control group; the total hospitalization time: 33 days in group VSD, 53 days in the control group; wound healing: 29 cases in VSD group, 12 cases in the control group; prolonged healing after dressing: 16 cases in VSD group, 13 cases in the control group; after skin grafting healing: 9 cases in VSD group, 17 cases in the control group; healed after flap transposition: 2 cases in VSD group and 10 cases in thecontrol group.The difference of the data of the two groups was statistically significant, P <0.05.Maryland foot score: 55-98 (average: 88.8, median: 91.5) points in VSD group, 38-97 (average: 84.85, median: 91) points in control group, compared with median by rank sum test, Z value: -2.755, the difference was statistically significant, P < 0.05.The late recovery effect rating: 39 casesexcellent, good 12 cases, can be 5 cases, no poor in VSD group, excellent 29 cases, good 8 cases, can be 11 cases, poor 4 cases in the the control group, the difference was statistically significant, P <0.05. Conclusion: VSD can shorten the preoperative waiting time and total hospitalization time, improve the wound healing rate directly, reduce the skin grafting and flap transfer replacement rate, reduce the secondary injury, increased fracture risk reduction and internal fixation, reduce joint fusion rate in the treatment of foot closed complex fracture and dislocation with severe soft tissue injury.

Objective: To observe the clinical effect of vacuum sealing drainage (VSD) technique and simple dressing change in the treatment of delayed severe infection after calcaneal fracture surgery. Methods: From August 2008 to July 2015 , 73 patients with delayed severe infection were treated after calcaneal fractures 3 months in Department of Foot and Ankle, the Second Hospital of Tangshan City, according to the treatment methods are divided into vacuum sealing drainage group of 38 cases, 35 cases of simple dressing group.Two groups of patients after regular wound debridement debridement and sterilization after vacuum sealing drainage group received double wound VSD dressing group received postoperative dressing, two groups of patients with sensitive antibiotics for treatment.Two groups of patients according to the frequency of dressing change, wound healing time, bacterial clearance time and healing time were compared in stage Ⅱ during the perioperative period. Results: Vacuum sealing drainage group: dressing: 7 times, the wound healing time was 27 days, bacterial culture negative for 8 days, the healing time of 13.5 days of perioperative period; treatment group: 34 times the number of dressing, wound healing time was 44 days, bacterial culture negative for 18 days, the healing time of 17 days of surgery period. Two groups of data were compared with the median, after the rank sum test, the difference was statistically significant ( Z values were -6.670, -5.529, -5.011, -3.227, P <0.05). The vacuum sealing drainage group compared with conventional dressing group significantly reduced the number of dressing, wound healing time, healing time was significantly shortened bacterial clearance time and perioperative period Ⅱ. Conclusion: Double VSD is easy , safe and quick, short cure time, less pain, higher quality of late life advantages, compared with the traditional dressing treatment of calcaneal fractures of postoperative delayed severe infection, is a safe and effective method.

Background: Polypoidal choroidal vasculopathy (PCV) is characterized by the presence of polyps with or without a branching vascular network and more prevalent among Asians. The aim of this study was to compare the outcomes of conbercept therapy between two different angiographic subtypes of PCV., Methods: Fifty-eight patients of PCV were classified into two phenotypes according to indocyanine green angiography (ICGA). In Type 1, both feeder and draining vessels are visible on ICGA and network vessels are numerous. In Type 2, neither feeder nor draining vessels are detectable, and the number of network vessels is small. The patients were treated with intravitreal conbercept (IVC) for 3 months. Additional IVC was given at subsequent monthly visits, if needed. The patients were followed up for 12 months, and changes in mean best-corrected visual acuity (BCVA), central retinal thickness (CRT), subretinal fluid (SRF) thickness, pigmented epithelial detachment (PED), hemorrhage, and number of polypoidal lesions were evaluated., Results: The mean BCVA in Type 2 PCV (15.92 ± 9.76 letters) achieved a significantly greater improvement than that in the Type 1 (14.10 ± 9.07 letters) at month 12 (t = 2.37, P< 0.01). Moreover, the mean CRT decrease was numerically greater in Type 2 (120.44 ± 73.81 μm) compared with Type 1 (106.48 ± 72.33 μm) at month 6 (t = 4.31, P< 0.01), and greater in Type 2 (130.21 ± 76.28 μm) compared with Type 1 (111.67 ± 79.57 μm) at month 9 (t = 1.87, P< 0.01). There was no significant difference between the two types for the decrease in SRF thickness, PED height, and regression of polyps from month 3 to 12 (t = 2.97, P > 0.05)., Conclusion: Classification systems for PCV will show differences in presentation, natural history, or response to anti-vascular endothelial growth factor treatment and might, therefore, provide a new key to the choice of treatment for the disease.

Background: Intracranial atherosclerosis (ICAS) is a common etiology of ischemic stroke in Chinese patients, probably leading to regional hypoperfusion in the brain. The purpose of this prospective study was to investigate the association between ICAS and poststroke depression in Chinese patients with ischemic stroke., Methods: During the study period, a total of 569 patients aged between 40 and 80 years with acute ischemic stroke were consecutively admitted and screened. Patients with a National Institutes of Health Stroke Scale (NIHSS) total score of 15 or higher, with severe cognitive impairment, or with a history of depression before stroke were excluded. Two hundred seven patients with ischemic stroke were consecutively recruited in the study. Depressive symptoms were assessed in the acute stage and 3 months after stroke. Poststroke depression was defined as a score of 8 or higher in the 24-item Hamilton Depression Rating Scale. The evaluation of the magnetic resonance imaging scans focused on infarctions, white matter lesions, brain atrophy, and ICAS., Results: In the acute stage of stroke, logistic regression revealed that female sex, NIHSS score at admission, prestroke insomnia, and ICAS were significant predictors of poststroke depression. At 3 months after stroke, prestroke insomnia, the Mini-Mental State Examination score and ICAS were significant predictors of poststroke depression., Conclusions: ICAS may be a significant independent predictor of poststroke depression in Chinese patients with ischemic stroke., (Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Relative primary acoustic gas thermometry (AGT) determines the ratios of thermodynamic temperatures from measured ratios of acoustic and microwave resonance frequencies in a gas-filled metal cavity on isotherms of interest. When measured in a cavity with known dimensions, the frequencies of acoustic resonances in a gas determine the speed of sound, which is a known function of the thermodynamic temperature T. Changes in the dimensions of the cavity are measured using the frequencies of the cavity's microwave resonances. We explored techniques and materials for AGT at high temperatures using a cylindrical cavity with remote acoustic transducers. We used gas-filled ducts as acoustic waveguides to transmit sound between the cavity at high temperatures and the acoustic transducers at room temperature. We measured non-degenerate acoustic modes in a cylindrical cavity in the range 295 K

Background: Fatigue is a common problem in ischemic stroke survivors. The mechanisms of poststroke fatigue are uncertain yet. The effects of it on functional status have rarely been studied., Aims: The aim of this study was to investigate the risk factors of poststroke fatigue and its effect on activities of daily living and health-related quality of life in Chinese patients with ischemic stroke., Methods: Two hundred and eighteen patients with ischemic stroke formed the study sample. A comprehensive assessment, including the Fatigue Severity Scale, Hamilton Depression Rating Scale, Lawton activities of daily living scale, and the stroke-specific quality of life scale, was conducted three-months after stroke. Magnetic resonance imaging scans focused on the evaluation of infarctions, white matter lesions, and brain atrophy., Results: In the whole sample, with Fatigue Severity Scale as the dependent variable in a linear regression model, Hamilton Depression Rating Scale, prestroke fatigue, and the National Institutes of Health Stroke Scale score at admission were significant correlates of Fatigue Severity Scale, accounting for 36% of the variance of it. When subjects with depression (Hamilton Depression Rating Scale ≥ 20 or current usage of antidepressants) were excluded, only Hamilton Depression Rating Scale and prestroke fatigue remained significant correlates of Fatigue Severity Scale, accounting for 33% of the variance of Fatigue Severity Scale. No magnetic resonance imaging variables correlated with Fatigue Severity Scale. In bivariate correlation analyses, Fatigue Severity Scale was significantly correlated with both activities of daily living and stroke-specific quality of life. In linear regression models, Fatigue Severity Scale independently contributed to activities of daily living accounting for 27% of the variance. Fatigue Severity Scale was also a significant contributor to stroke-specific quality of life accounting for 39% of the variance., Conclusion: Depressive symptoms and prestroke fatigue are major correlates of poststroke fatigue while more severe poststroke fatigue is associated with poorer activities of daily living and health-related quality of life., (© 2014 World Stroke Organization.)

Objectives: The aim of the present study was to explore the magnetic resonance imaging correlates of the performance of instrumental activities of daily living (IADL) in patients with Alzheimer's disease combined with cerebrovascular disease., Methods: A total of 66 patients with Alzheimer's disease combined with cerebrovascular disease formed the study sample. Two regression models were constructed to find correlates of IADL. Model 1 only included clinical variables and model 2 included both clinical and magnetic resonance imaging variables., Results: In model 1, with IADL as the dependent variable, the Mini-Mental State Examination (MMSE) score, Physical Self-Maintenance Scale score at baseline and age were significant correlates accounting for 40.1% of the variance of IADL at baseline. MMSE score and age were also significant correlates of IADL at 6 months, accounting for 38.1% of the variance of it. In model 2, severity of white matter lesions, MMSE and Physical Self-Maintenance Scale scores at baseline significantly correlated with IADL at baseline, accounting for 52.1% of the variance of the dependent variables; severity of white matter lesions and MMSE significantly correlated with IADL at 6 months, accounting for 41.5% of the variance of the dependent variables., Conclusion: In patients with Alzheimer's disease combined with cerebrovascular disease, subcortical ischemic lesions might be significant contributor to the functional status., (© 2014 Japan Geriatrics Society.)

Background: Gadolinium chloride (GdCl3) selectively inactivates Kupffer cells and protects against ischemia/reperfusion and endotoxin injury. However, the effect of Kupffer cell inactivation on liver regeneration after partial liver transplantation (PLTx) is not clear. This study was to investigate the role of GdCl3 pretreatment in graft function after PLTx, and to explore the potential mechanism involved in this process., Methods: PLTx (30% partial liver transplantation) was performed using Kamada's cuff technique, without hepatic artery reconstruction. Rats were randomly divided into the control low-dose (5 mg/kg) and high-dose (10 mg/kg) GdCl3 groups. Liver injury was determined by the plasma levels of alanine aminotransferase and aspartate aminotransferase, liver regeneration by PCNA staining and BrdU uptake, apoptosis by TUNEL assay. IL-6 and p-STAT3 levels were measured by ELISA and Western blotting., Results: GdCl3 depleted Kupffer cells and decreased animal survival rates, but did not significantly affect alanine aminotransferase and aspartate aminotransferase (P>0.05). GdCl3 pretreatment induced apoptosis and inhibited IL-6 overexpression and STAT3 phosphorylation after PLTx in graft tissues., Conclusion: Kupffer cells may contribute to the liver regeneration after PLTx through inhibition of apoptosis and activation of the IL-6/p-STAT3 signal pathway.

Unlabelled: Keratocystic odontogenic tumors (KCOTs) are jaw lesions that can be either sporadic or associated with nevoid basal cell carcinoma syndrome, which typically occurs as multiple, aggressive lesions that can lead to large areas of bone destruction and resorption and cause major impairment and even jaw fracture. To clarify the role of fibroblasts in the aggressivness of syndromic (S-) as compared with non-syndromic (NS-) KCOTs, we assessed fibroblasts derived from 16 S- and NS-KCOTs for differences in cell proliferation, multilineage differentiation potential, alkaline phosphatase activity, and osteoclastogenic potential. S-KCOT fibroblasts had proliferative and osteoclastogenic capacity higher than those from NS-KCOTs, as evidenced by higher numbers of tartrate-resistant acid-phosphatase-positive multinuclear cells, expression of cyclooxygenase 2, and ratio of receptor activator of nuclear factor-kappa B ligand to osteoprotegerin. The osteogenic potential was higher for S- than for NS-KCOT fibroblasts and was associated with lower mRNA expression of runt-related transcription factor 2, collagen type I α1, osteocalcin, and osteopontin as well as reduced alkaline phosphatase activity. These results suggest that the distinct characteristics of fibroblasts in KCOTs are responsible for the greater aggressiveness observed in the syndromic subtype., Abbreviations: AP, alkaline phosphatase; CK, cytokeratin; COL1A1, collagen type I α1; COX-2, cyclooxygenase-2; GM-CSF, granulocyte-macrophage colony-stimulating factor; IL-1α, interleukin 1α; KCOT, keratocystic odontogenic tumor; NBCCS, nevoid basal cell carcinoma syndrome; NS-KCOT, non-syndrome-associated KCOT; OCN, osteocalcin; OPG, osteoprotegerin; OPN, osteopontin; RANKL, receptor activator of nuclear factor-kappa B ligand; Runx2, runt-related transcription factor 2; S-KCOT, syndrome-associated KCOT; TAF, tumor-associated fibroblast; and TRAP, tartrate-resistant acid phosphatase., (© International & American Associations for Dental Research.)

Mutations in the transmembrane receptor patched homolog 1 (Homo sapiens) (ptch1) are responsible for nevoid basal cell carcinoma syndrome (NBCCS), an autosomal dominant disorder that causes developmental abnormalities and predisposes the affected individuals to cancer. Many of these mutations, including mutations in the C-terminus of the large intracellular loop (ICL) of ptch1 (p.C727VfsX745 and p.S733IfsX736), result in the premature truncation of the protein. The ptch1‑C727VfsX745 and ptch1-S733IfsX736 mutations have been identified in patients with NBCCS‑associated keratocystic odontogenic tumors (KCOTs). In the present study, we found that the molecular mechanisms regulated by the non-canonical Hedgehog (Hh) signaling pathway through cyclin B1 are involved in the pathogenesis of NBCCS-associated KCOTs. In contrast to wild-type ptch1, ptch1-C727VfsX745 and ptch1‑S733IfsX736 clearly exhibited reduced binding to cyclin B1. Moreover, the cells expressing these two mutations demonstrated an increase in cell cycle progression and these two mutation constructs failed to inhibit cell proliferation. In addition, the mutants enhanced the activity of glioma-associated oncogene family zinc finger 1 (GLI1), a downstream reporter of Hh signaling. Thus, our data suggest that the non-canonical Hh pathway mediated through ptch1 and cyclin B1 is involved in the pathogenesis of NBCCS-associated KCOTs. The C-terminus of ICL in ptch1 may also be a potential therapeutic target in the treatment of this disease.

Tai Ding Yang Sheng Zhu Lun is a monograph of life-cultivation, written by Wang Gui of the Yuan Dynasty. Wang Gui held that life-cultivation should start from marriage and pregnancy, so paid great attention to them. His thoughts reflected on marriage at an appropriate age, pregnancy at a selected time, emphasizing the health of the foetus, the priority of enriching the mind, timely care of pregnant women, etc. All of these reflect the ancient concepts of eugenics.

Pre-exposure to lipopolysaccharide (LPS) leads to hyposensitivity to secondary LPS stimulation, known as endotoxin tolerance. The role of macrophage scavenger receptor-A (SR-A) in endotoxin tolerance is unknown. In this study, LPS was shown to induce SR-A expression in the mouse macrophage cell line, RAW264.7, in dose- and time-dependent manners, which correlated with inflammatory cytokine suppression in RAW264.7 on secondary LPS stimulation. Over-expression of SR-A in RAW264.7 suppressed tumour necrosis factor (TNF)-alpha release and nuclear factor (NF)-kappa B activation, demonstrating the involvement of SR-A in endotoxin tolerance. LPS-pre-treated RAW264.7 cells could bind and internalize more fluorescein isothiocyanate (FITC)-LPS than untreated cells and both the SR-A ligand, fucoidan, and anti-SR-A 2F8 antibodies completely suppressed LPS-induced binding and internalization of FITC-LPS by RAW264.7. LPS-induced SR-A expression on RAW264.7 was completely suppressed by the p38-specific inhibitor, SB203580, but not by inhibition of toll-like receptor 4 (TLR4) signalling with MTS510, demonstrating that p38- but not TLR4-dependent up-regulation of SR-A was involved in endotoxin tolerance through binding and internalization of LPS.