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Abstract Background Cryptococcosis is an infectious disease caused by encapsulated heterobasidiomycete yeasts. As an opportunistic pathogen, cryptococcal inhalation infection is the most common. While Primary cutaneous cryptococcosis is extremely uncommon. Case presentation A 61-year-old woman with a history of rheumatoid arthritis on long-term prednisone developed a red plaque on her left thigh. Despite initial antibiotic treatment, the erythema worsened, leading to rupture and fever. Microbiological analysis of the lesion’s secretion revealed Candida albicans, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus epidermidis. Skin biopsy showed thick-walled spores, and culture confirmed primary cutaneous infection with Cryptococcus neoformans. Histopathological stains were positive, and mass spectrometry identified serotype A of the pathogen. The patient was treated with oral fluconazole and topical nystatin, resulting in significant improvement and near-complete healing of the skin lesion within 2.5 months. Conclusions Primary cutaneous cryptococcosis was a primary skin infection exclusively located on the skin. It has no typical clinical manifestation of cutaneous infection of Cryptococcus, and culture and histopathology remain the gold standard for diagnosing. The recommended medication for Primary cutaneous cryptococcosis is fluconazole. When patients at risk for opportunistic infections develop skin ulcers that are unresponsive to antibiotic, the possibility of primary cutaneous cryptococcosis needs to be considered.

Background: Severe cutaneous adverse reactions (SCARs) including acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) and its related diseases, and toxic epidermal necrolysis (TEN) are of great concern due to their high mortality rates. While systemic corticosteroids have been widely used to treat SCARs, their efficacy has been debated due to the increased risk of infection. In recent years, tumor necrosis factor (TNF)-α inhibitors have emerged as a new therapeutic option.Objectives: This study aimed to report the clinical outcomes of different types of SCARs treated with TNF-α inhibitors.Methods: Since 2020, our department has treated 4 SCAR patients, aged 20-54 years, with 1 diagnosed with AGEP and 3 with TEN. All patients received TNF-α inhibitor therapy, including etanercept and adalimumab.Results: All 4 patients achieved successful outcomes, with rapid recovery of skin lesions and mucosal involvement, and no subsequent complications. Notably, one patient improved after initial corticosteroid and intravenous immunoglobulin treatment failed.Discussion: The pathogenesis of SCARs involves T cell-mediated keratinocyte apoptosis, in which TNF-α plays a crucial role. TNF-α inhibitors, by downregulating the TNF-α signaling pathway, have demonstrated potential in the treatment of SCARs. However, large-scale clinical trials supporting their efficacy are still lacking, and their use remains limited, requiring a careful balance of treatment risks and benefits.

Abstract Objective Thromboangiitis obliterans (TAO) remains clinical challenging due to its rarity and underwhelming management outcomes. This study aimed to describe a novel TAO rabbit model that demonstrates a closer resemblance to TAO. Methods Thirty-six New Zealand rabbits underwent the surgical implantation of calibrated gelatin sponge particles (CGSPs) into their right femoral artery. The CGSPs were soaked in different solutions to simulate different types of thrombi: normal (NT; normal saline); inflammatory TAO thrombus (TAO; dimethylsulfoxide [DMSO]), and DMSO with methotrexate (MTX). All groups underwent clinical assessment, digital subtraction angiography (DSA) and histopathological analysis at time points day 0 (immediate), week 1 (acute), week 2 (subacute), and week 4 (chronic). Results The TAO rabbit presented with signs of ischemia of the right digit at week 4. On DSA, the TAO rabbits exhibited formation of corkscrew collaterals starting week 1. On H&E staining, gradual CGSP degradation was observed along with increased red blood cell aggregation and inflammatory cells migration in week 1. On week 2, disorganization of the tunica media layer and vascular smooth muscle cell (VSMC) proliferation was observed. In the TAO rabbit, migrated VSMCs, inflammatory cells, and extracellular matrix with collagen-like substances gradually occluded the lumen. On week 4, the arterial lumen of the TAO rabbit was filled with relatively-organized VSMC and endothelial cell clusters with less inflammatory cells. Neorevascularization was found in the MTX-treated group. Conclusion The novel TAO rabbit model shows a closer resemblance to human TAO clinically, radiographically, and histopathologically. Histological analysis of the IT progression in the TAO model suggests that it is of VSMC origin.

Abstract The combination of macrocyclic chemistry with co-crystal engineering has promoted the development of materials with vapochromic behaviors in supramolecular science. Herein, we develop a macrocycle co-crystal based on hybrid[4]arene and 1,2,4,5-tetracyanobenzene that is able to construct vapochromic materials. After the capture of benzene and toluene vapors, activated hybrid[4]arene-based co-crystal forms new structures, accompanied by color changes from brown to yellow. However, when hybrid[4]arene-based co-crystal captures cyclohexane and pyridine, neither structures nor colors change. Interestingly, hybrid[4]arene-based co-crystal can separate benzene from a benzene/cyclohexane equal-volume mixture and allow toluene to be removed from a toluene/ pyridine equal-volume mixture with purities reaching 100%. In addition, the process of adsorptive separation can be visually monitored. The selectivity of benzene from a benzene/cyclohexane equal-volume mixture and toluene from a toluene/ pyridine equal-volume mixture is attributed to the different changes in the charge-transfer interaction between hybrid[4]arene and 1,2,4,5-tetracyanobenzene when hybrid[4]arene-based co-crystal captures different vapors. Moreover, hybrid[4]arene-based co-crystal can be reused without losing selectivity and performance. This work constructs a vapochromic material for hydrocarbon separation.

Abstract Considering the growing demand for electricity in industrial parks, understanding their electric power load patterns is critical for improving energy efficiency and ensuring the rational utilization of energy resources. However, the detailed electric power load data of various buildings in industrial parks are rarely available and accessible, which hinders the related studies. In this context, we present the electric power load data of 6 years (from January 1, 2016 to December 31, 2021) for various types of buildings in an industrial park in Suzhou, China. The data are obtained from smart meters and have various time resolutions (i.e., 5 minutes, 30 minutes, and 1 hour). This work describes the data collection, processing process, and different imputation methods. The high-resolution electric power load data can be used for various research tasks, including load prediction, load pattern recognition, anomaly detection, and demand response strategy development.

Component identification and depth estimation are important for detecting the integrity of post-disaster structures. However, traditional manual methods might be time-consuming, labor-intensive, and influenced by subjective judgments of inspectors. Deep-learning-based image visual inspection is a new approach to overcome these problems, but repeated modeling is required for different inspection tasks, which limits inspection accuracy and practical deployment efficiency. In this study, it is observed that the matched ratios of pixel pairs between component identification and depth estimation reach a high value, which indicates the dual tasks are highly related. Therefore, the Multi-Scale Task Interaction Network (MTI-Net) is proposed for structural images to simultaneously accomplish both tasks for accurate and efficient structural inspection. It propagates distilled task information from lower to higher scales. Then, it aggregates the refined task features from all scales to produce the final per-task predictions. Experiments show that MTI-Net delivers the full potential of multi-task learning, with a smaller memory footprint and higher efficiency compared to single-task learning. For the evaluation metrics of model performance, the mean Intersection over Union (mIoU) of component identification improves by 2.30, and root mean square error (RMSE) drops by 0.36 m with the aid of the multi-task strategy. The multi-task deep learning framework has great potential value in engineering applications.

Abstract This review aimed to explore the concept, etiology, classification, classical cortical mapping, assessment, diagnosis and differential diagnosis, treatment, rehabilitation, mechanism, recovery, prognosis, and influencing factors for Chinese post‐stroke aphasia (PSA). The review emphasized the necessity and significance of neuroimaging assessment of brain and blood vessels and neuropsychological assessment in diagnosis and differential diagnosis of Chinese PSA. In addition, it suggested and recommended to use “dichotomies of internal and external, and anterior and posterior” as a starting point, based on the anatomic location of brain and blood vessels and their relationship with language area and language disorder. As a result, the formulated Chinese PSA classification was more suitable to guide the clinical treatment of cerebral stroke. Diagnosis, classification, and differential diagnosis of Chinese PSA types were performed according to the “dichotomy” and “four elements.” The formulated “flow diagram” enabled to determine the classification of Chinese PSA types. It was beneficial for patients to establish targeted and individualized rehabilitation training plans. This review introduced the use of memantine, piracetam, donepezil, etc. in PSA treatment, evaluated clinical studies conducted in China and abroad, investigated the mechanism of action related to the use of drugs in PSA treatment, and explored the therapeutic mechanism of rehabilitation training. It suggested the use drugs of memantine, piracetam, donepezil, etc. combine with non‐pharmacotherapy and rehabilitation training in clinical studies on PSA treatment and also in practical settings.

Muntjac deer underwent rapid species radiation and dramatic chromosome fusions within a short period of time. Here the authors reveal that repeat sequences likely mediated illegitimate recombination to result in chromosome fusions and that 3D chromatin architecture around fusion sites have no significant change, while significant interactions across fusion sites were gradually established after speciation.

LNG is considered a promising alternative fuel for the marine industry with the increasingly strict environmental requirements while the safety problems caused by LNG leakage accidents need to be concerned and analyzed. In this article, the cryogenic safety analysis of the fuel gas preparation room in an LNG-powered ship during LNG leakage accidents was performed by CFD simulations. The simulation results showed as follows: the range of cryogenic region in the fuel gas preparation room was related to flow field direction during LNG leakage; The surface temperature of equipment dropped to some extent during LNG leakage accidents. The temperature drop was less than 15°C, which was confirmed to be a safe temperature range in engineering; In addition, for safety operation analysis, the NG distribution situation of dangerous regions with explosive limit was also obtained.

This article presents an umbrella review of blockchain-based smart grid applications. By umbrella review, we mean that our review is based on systematic reviews of this topic. We aim to synthesize the findings from these systematic reviews and gain deeper insights into this discipline. After studying the systematic reviews, we find it imperative to provide a concise and authoritative description of blockchain technology because many technical inaccuracies permeate many of these papers. This umbrella review is guided by five research questions. The first research question concerns the types of blockchain-based smart grid applications. Existing systematic reviews rarely used a systematic method to classify these applications. To address this issue, we propose a taxonomy of these applications, first by differentiating them based on whether the application is focusing on functional or non-functional aspects of smart grid operations, and then by the specific functions or perspectives that the application aims to implement or enhance. The second research question concerns the roles that blockchain technology plays in smart grid applications. We synthesize the findings by identifying the most prominent benefits that blockchain technology could bring to these applications. We also take the opportunity to point out several common technical mistakes that pervade the blockchain literature, such as equating all forms of blockchains to data immutability. The third research question concerns the guidelines for deciding whether a blockchain-based solution would be useful to address the needs of smart grids. We synthesize the findings by proposing benefit-based guidelines. The fourth research question concerns the maturity levels of blockchain-based smart grid applications. We differentiate between academic-led and industry-led projects. We propose a five-level scale to evaluate the maturity levels. The ranking of the industry-led projects is performed through our own investigation. Our investigation shows that more than half of the industry-led projects mentioned in the systematic reviews are no longer active. Furthermore, although there are numerous news reports and a large number of academic papers published on blockchain-based smart grid applications, very few have been successfully embraced by the industry. The fifth research question concerns the open research issues in the development of blockchain-based smart grid applications. We synthesize the findings and provide our own analysis.

Primary progressive aphasia (PPA), typically resulting from a neurodegenerative disease, is characterized by a progressive loss of specific language functions while other cognitive domains are relatively unaffected. The logopenic variant, characterized by impairments of word retrieval and sentence repetition along with preserved semantic, syntactic, and motor speech abilities, is the most recently described and remains less understood than other variants due to a comparatively small number of case studies and a lack of investigations with a thorough specification. In this article, we report a 2-year follow-up case study of a 74-year-old Chinese female patient with a logopenic variant of primary progressive aphasia, including its neurolinguistic study, magnetic resonance imaging (MRI), and 11C-Pittsburgh compound B-Positron emission tomography imaging analyses, as well as gene sequencing. This case confirms that, in addition to word-finding and sentence repetition difficulties, the logopenic variant may also present with mild auditory comprehension and naming deficits attributed to impaired access to lexical representations. The observation of clinical treatment suggests the efficacy of memantine hydrochloride tablet and rivastigmine transdermal patch in slowing down the cognitive deterioration of this patient. The description and exploration of this case may shed new insights into a better understanding of the Chinese logopenic variant of primary progressive aphasia.

The development of supramolecular chemistry has always been accompanied by the innovation of macrocyclic hosts. The synthesis of novel macrocycles with unique structures and functions will bring new development opportunities for supramolecular chemistry. As a new generation of macrocyclic hosts, biphenarenes have customizable cavity sizes and diverse backbones, overcoming the limitation that the cavities of traditionally popular macrocyclic hosts are generally smaller than 10 Å. These features undoubtedly endow biphenarenes with distinguished host–guest properties, which have attracted more and more attention. In this review, the structural characteristics and molecular recognition properties of biphenarenes are summarized. In addition, the applications of biphenarenes in adsorption and separation, drug delivery, fluorescence sensing and other fields are introduced. Hopefully, this review will provide a reference for the study of macrocyclic arenes, especially biphenarenes.

Background: This study compared the epidemiology of carbapenem-resistant (CRKP) and carbapenem-sensitive (CSKP) K. pneumoniae bloodstream infections (BSIs), and assessed risk factors for 28-day mortality of patients with K. pneumoniae BSIs. Methods: A retrospective cohort study was conducted in a 2000-bed tertiary teaching hospital of Beijing between Jan 1st 2013 to Dec 31st, 2019. All patients with K. pneumoniae BSI were identified through the Hospital Information System. The endpoints included incidence rate, mortality and risk factors for mortality of patients with K. pneumoniae BSIs. Results: 496 patients with K. pneumoniae BSIs were included in the analysis, with 108 CRKP BSIs. The incidence rate of K. pneumoniae BSI was 10.6 (CI: 9.7, 11.6) per 100 000 patient-days, with the rate for CRKP BSI was 2.3 (95% CI: 1.9, 2.8). The 28-day mortality was 38.0% for CRKP BSI and 8.8% for CSKP BSI, respectively. Logistic analysis showed, higher Charlson Comorbidity Index score (OR = 1.26, 95%CI 1.12–1.43, p < 0.001), respiratory failure (OR = 2.73, 95%CI1.28−5.84, p = 0.010), renal failure (OR = 4.13, 95%CI1.93−8.83, p < 0.001), septic shock (OR = 8.77, 95%CI3.60−21.32, p < 0.001), mechanical ventilation (OR = 4.41, 95%CI1.59−12.25, p = 0.004) and CRKP infection (OR = 3.04, 95%CI1.28−7.22, p = 0.012) were independently associated with 28-day mortality. Conclusions: Considerable incidence rate and remarkable mortality of patients with K. pneumoniae (especially CRKP) BSI was declared in the study. Patient conditions before (higher CCI) and after presentation (respiratory failure, renal failure, septic shock), and healthcare factors (mechanical ventilation and CRKP infection) were independently associated with 28-day mortality. Understanding these risks helps better establishment of infection control strategies.

BackgroundThe increasing prevalence of Alzheimer’s disease (AD) has emerged as a major challenge worldwide. China as the most populous country in the globe is amid rapid aging of its population, highlighting the need for appropriate social and medical policies to meet the challenge. The current multicenter cross-sectional observational study aims to provide understanding of the current status of caring given to AD patients in China and investigate the factors that influence the family burden as well as the choice of care given to AD patients.MethodsA total of 1,675 patients with probable AD from 30 provincial regions of mainland China were enrolled in the current study from August 2019 to December 2019. We analyzed the caregiving status and its relationship with family burden and various socio-economical and medical factors.ResultsIn the current study, 90.87% of the AD patients enrolled adopted family care. The choice of caregiving method was influenced by factors including age (>80 years old, OR 0.648; 95% CI, 0.427–0.983), overall family burden (high, OR 0.574; 95% CI, 0.0.373–0.884), patients’ income (OR 0.511; 95% CI, 0.330–0.789) and self-care ability (OR 0.329; 95% CI, 0.183–0.588).ConclusionFamily care is the primary method of care for AD patients in China and the institutional care system for AD patients is still underprepared in China.

Supramolecular polymers have attracted considerable interest due to their intriguing features and functions. The dynamic reversibility of noncovalent interactions endows supramolecular polymers with tunable physicochemical properties, self-healing, and externally stimulated responses. Among them, pillararene-based supramolecular polymers show great potential for biomedical applications due to their fascinating host–guest interactions and easy modification. Herein, we summarize the state of the art of pillararene-based supramolecular polymers for cancer therapy and illustrate its developmental trend and future perspective.

Abstract Background Individuals with subjective memory complaints (SMC) feature a higher risk of cognitive decline and clinical progression of Alzheimer’s disease (AD). However, the pathological mechanism underlying SMC remains unclear. We aimed to assess the intrinsic connectivity network and its relationship with AD-related pathologies in SMC individuals. Methods We included 44 SMC individuals and 40 normal controls who underwent both resting-state functional MRI and positron emission tomography (PET). Based on graph theory approaches, we detected local and global functional connectivity across the whole brain by using degree centrality (DC) and eigenvector centrality (EC) respectively. Additionally, we analyzed amyloid deposition and tauopathy via florbetapir-PET imaging and cerebrospinal fluid (CSF) data. The voxel-wise two-sample T-test analysis was used to examine between-group differences in the intrinsic functional network and cerebral amyloid deposition. Then, we correlated these network metrics with pathological results. Results The SMC individuals showed higher DC in the bilateral hippocampus (HP) and left fusiform gyrus and lower DC in the inferior parietal region than controls. Across all subjects, the DC of the bilateral HP and left fusiform gyrus was positively associated with total tau and phosphorylated tau181. However, no significant between-group difference existed in EC and cerebral amyloid deposition. Conclusion We found impaired local, but not global, intrinsic connectivity networks in SMC individuals. Given the relationships between DC value and tau level, we hypothesized that functional changes in SMC individuals might relate to pathological biomarkers.

It is challenging to design photosensitizers (PS) with high quantum yields generating singlet oxygen due to severe aggregation between the hydrophobic PSs. Here they develop organoplatinum(II) metallatocage-based PS to overcome these challenges and show excellent antitumor effect.

Background: The National Institute on Aging-Alzheimer’s Association (NIA-AA) has proposed a biological definition of Alzheimer’s disease (AD): individuals with both abnormal amyloid and tau biomarkers (A+T+) would be defined as AD. It remains unclear why different cognitive status is present in subjects with biological AD. Resting-state functional magnetic resonance imaging (rsfMRI) has provided an opportunity to reveal the brain activity patterns in a biologically-defined AD cohort. Accordingly, we aimed to investigate distinct brain activity patterns in subjects with existed AD pathology but in the different cognitive stages.Method: We selected individuals with AD pathology (A+T+) and healthy controls (HC, A−T−) based on the cerebrospinal fluid (CSF) biomarkers. According to the cognitive stage, we divided the A+T+ cohort into three groups: (1) preclinical AD; (2) prodromal AD; and (3) AD with dementia (d-AD). We compared spontaneous brain activity measured by a fractional amplitude of low-frequency fluctuation (fALFF) approach among four groups.Results: The analysis of covariance (ANCOVA) results showed significant differences in fALFF in the posterior cingulate cortex/precuneus (PCC/PCu). Further, compared to HC, we found increased fALFF values in the right inferior frontal gyrus (IFG) in the preclinical AD stage, whereas prodromal AD patients showed reduced fALFF in the bilateral precuneus, right middle frontal gyrus (MFG), right precentral gyrus, and postcentral gyrus. Within the d-AD group, both hyperactivity (right fusiform gyrus, right parahippocampal gyrus (PHG)/hippocampus, and inferior temporal gyrus) and hypoactivity (bilateral precuneus, left posterior cingulate cortex, left cuneus and superior occipital gyrus) were detected.Conclusion: We found the distinct brain activity patterns in different cognitive stages among the subjects defined as AD biologically. Our findings may be helpful in understanding mechanisms leading to cognitive changes in the AD pathophysiological process.

Background The biological diagnosis criteria of the Alzheimer’s disease (AD) suggests that previous work may misclassify the cognitive impairment caused by other factors into AD. Consequently, re-assessing the imaging profile of AD continuum is needed. Considering the high vulnerability of cortical association fibers, we aimed to elucidate the cortical demyelination process in the AD continuum biologically defined.Methods According to the biological diagnosis criteria, we determined the positive amyloid status (A+) as cerebrospinal fluid (CSF) amyloid1–42 < 192 pg/ml, Florbetapir Positron emission tomography (PET) composite standardized uptake value ratio (SUVR) >1.11. Also, the positive Tau status (T+) was determined as p-Tau181 > 23 pg/ml. Based on the cognitive characterization, we further categorized 252 subjects into 27 cognitively unimpaired with normal AD biomarkers (A−T−, controls), 49 preclinical AD (A+T+), 113 AD with mild cognitive impairment (MCI) (A+T+), and 63 AD dementia (A+T+). We estimated the intracortical myelin content used the T1- and T2-weighted (T1W/T2W) ratio mapping. To investigate the sensitivity of the ratio mapping, we also utilized well-validated AD imaging biomarkers as the reference, including gray matter volume and Fludeoxyglucose PET (FDG-PET). Based on the general linear model, we conducted the voxel-wise two-sample T-tests between the controls and each group in the AD continuum.Results Compared to the controls, the results showed that the preclinical AD patients exhibited decreased T1W/T2W ratio value in the right inferior parietal lobule (IPL); as the disease progresses, the prodromal AD patients demonstrated lower ratio value in bilateral IPL, with hippocampus (HP) atrophy. Lastly, the AD dementia patients exhibited decreased ratio value in bilateral IPL and hippocampus; also, we observed the bilateral temporal cortices atrophy and widespread decreased metabolism in the AD dementia patients. After corrected with gray volume, the results remained mostly unchanged.Conclusion Our study implied the decreased right IPL T1W/T2W ratio might represent early AD-related demyelination in disease continuum. Additionally, we demonstrated that the T1W/T2W ratio mapping is an easy-to-implement and sensitive metric to assess the intracortical myelin content in AD, particularly in the early stage.

Psoriasis is a T-cell mediated disease that involves IL-23/Th17 and IL-12/Th1 axes. Ustekinumab, a fully human monoclonal antibody targeting the p40 subunit of both IL-12 and IL-23, has proven to be efficient and safe for treating patients with psoriasis. Yet, there have been no reports with human skin/blood samples that would elucidate the molecular mechanisms by which ustekinumab calms psoriasis skin lesions. To investigate the efficacy and molecular pathway (RORC, t-BOX and GATA) of ustekinumab in treating patients with psoriasis skin lesions. A total of 30 patients with psoriasis were randomized into placebo group and treatment group. PASI of each patient was calculated at 0, 12 and 24 weeks post-treatment. The mRNA levels of RORC, t-BOX and GATA in peripheral blood mononuclear cells separated from patients’ whole blood were analyzed using qPCR. Decreased mRNA of RORC, t-BOX and GATA were observed after continuous injections, indicating that ustekinumab exerts its effect by interacting with these molecules; while no significant difference in foxp3 mRNA levels were found between placebo group and treatment group.

Alzheimer's disease (AD) has a long neuropathological accumulation phase before the onset of dementia. Such AD neuropathological deposition between neurons impairs the synaptic communication, resulting in networks disorganization. Our study aimed to explore the evolution patterns of gray matter structural covariance networks (SCNs) along AD continuum. Based on the AT(N) (i.e., Amyloid/Tau/Neurodegeneration) pathological classification system, we classified subjects into four groups using cerebrospinal fluid amyloid-beta1–42 (A) and phosphorylated tau protein181 (T). We identified 101 subjects with normal AD biomarkers (A-T-), 40 subjects with Alzheimer's pathologic change (A + T−), 101 subjects with biological AD (A + T+) and 91 AD with dementia (demented subjects with A + T+). We used four regions of interest to anchor default mode network (DMN, medial temporal subsystem and midline core subsystem), salience network (SN) and executive control network (ECN). Finally, we used a multi-regression model-based linear-interaction analysis to assess the SCN changes. Along the disease progression, DMN and SN showed increased structural association at the early stage while decreased structural association at the late stage. Moreover, ECN showed progressively increased structural association as AD neuropathological profiles progress. In conclusion, this study found the dynamic trajectory of SCNs changes along the AD continuum and support the network disconnection hypothesis underlying AD neuropathological progression. Further, SCN may potentially serve as an effective AD biomarker. Keywords: Alzheimer's disease continuum, Gray matter structural covariance, AT(N) classification system, CSF, Tau protein, Amyloid

Background: Early-onset Alzheimer’s disease (EOAD) presents a different clinical profile than late-onset Alzheimer’s disease (LOAD). Neuroimaging studies have demonstrated that patients with EOAD present more atrophy and functional disconnection than LOAD patients. However, it remains unknown whether the interhemispheric functional disconnection or its underlying structural impairment contributes to the different clinical profiles of EOAD and LOAD.Methods: According to the arbitrary cut-off age of 65, we included 22 EOAD patients, 27 LOAD patients and 38 healthy controls (further divided into 21 relatively young and 17 old controls). Participants underwent resting-state functional MRI, diffusion tensor imaging (DTI) and comprehensive neuropsychological assessments. We used voxel-mirrored homotopic connectivity (VMHC) to examine interhemispheric functional connectivity. Then, we calculated the diffusion index based on tract-based spatial statistics (TBSS). Two-sample t-tests were used to assess the interhemispheric connectivity differences between each patient group and its corresponding control group.Results: We found that the EOAD patients had lower VMHC in the hippocampus, parahippocampal gyrus (PHG), superior temporal gyrus (STG) and inferior parietal cortex (IPC) than did controls. Consistently, the EOAD patients exhibited white matter (WM) tract impairment in the posterior regions. On the other hand, the LOAD patients displayed increased VMHC and impaired WM tracts in the frontal region. Correlation analyses showed that VMHC in the IPC was related to executive function in the EOAD patients (r = −0.67, P < 0.05).Conclusion: In contrast to the LOAD patients, patients with EOAD exhibited more widely disrupted interhemispheric functional and structural connectivity, which overlapped well across brain regions. In addition, for the EOAD patients, decreased interhemispheric connectivity related to executive deficits. Our study suggested that different interhemispheric connectivity damage patterns may contribute to the distinct clinical profiles in EOAD and LOAD.

Background: Amnestic mild cognitive impairment (aMCI) is a heterogeneous condition. Based on clinical symptoms, aMCI could be categorized into single-domain aMCI (SD-aMCI, only memory deficit) and multi-domain aMCI (MD-aMCI, one or more cognitive domain deficit). As core intrinsic functional architecture, inter-hemispheric connectivity maintains many cognitive abilities. However, few studies investigated whether SD-aMCI and MD-aMCI have different inter-hemispheric connectivity pattern.Methods: We evaluated inter-hemispheric connection pattern using fluorine-18 positron emission tomography – fluorodeoxyglucose (18F PET-FDG), resting-state functional MRI and structural T1 in 49 controls, 32 SD-aMCI, and 32 MD-aMCI patients. Specifically, we analyzed the 18F PET-FDG (intensity normalized by cerebellar vermis) in a voxel-wise manner. Then, we estimated inter-hemispheric functional and structural connectivity by calculating the voxel-mirrored homotopic connectivity (VMHC) and corpus callosum (CC) subregions volume. Further, we correlated inter-hemispheric indices with the behavioral score and pathological biomarkers.Results: We found that MD-aMCI exhibited more several inter-hemispheric connectivity damages than SD-aMCI. Specifically, MD-aMCI displayed hypometabolism in the bilateral middle temporal gyrus (MTG), inferior parietal lobe, and left precuneus (PCu) (p < 0.001, corrected). Correspondingly, MD-aMCI showed decreased VMHC in MTG, PCu, calcarine gyrus, and postcentral gyrus, as well as smaller mid-posterior CC than the SD-aMCI and controls (p < 0.05, corrected). Contrary to MD-aMCI, there were no neuroimaging indices with significant differences between SD-aMCI and controls, except reduced hypometabolism in bilateral MTG. Within aMCI patients, hypometabolism and reduced inter-hemispheric connectivity correlated with worse executive ability. Moreover, hypometabolism indices correlated to increased amyloid deposition.Conclusion: In conclusion, patients with MD-aMCI exhibited the more severe deficit in inter-hemispheric communication than SD-aMCI. This long-range connectivity deficit may contribute to cognitive profiles and potentially serve as a biomarker to estimate disease progression of aMCI patients.

Background: The clinical behavior and management of poorly differentiated thyroid carcinoma (PDTC) are very different from papillary thyroid carcinoma (PTC). By comparing the clinical and ultrasonographic features between the two tumors, we proposed to provide more possibilities for recognizing PDTC before treatment. Methods: The data of 13 PDTCs and 39 age- and gender-matched PTCs in Peking Union Medical College Hospital between December 2003 and September 2013 were retrospectively reviewed. The clinical and ultrasonic features between the two groups were compared. Results: The frequencies of family history of carcinoma, complication with other thyroid lesions, lymph node metastases, recurrent laryngeal nerve injuries, and distant metastases were higher in PDTCs (30.8%, 61.6%, 69.2%, 23.1%, and 46.2%, respectively) than those in PTCs (2.6%, 23.1%, 25.6%, 2.6%, and 2.6%, respectively) (P < 0.05). The mortality rate of PDTCs was greatly higher than PTCs (P < 0.01). Conventional ultrasound showed that the size of PDTCs was larger than that of PTCs (3.1 ± 1.9 cm vs. 1.7 ± 1.0 cm). Clear margins and rich and/or irregular blood flow were found in 92.3% of PDTCs, which differed substantially from PTCs (51.7% and 53.8%, respectively) (P < 0.05). Conclusions: PDTC is more aggressive and its mortality rate is higher than PTCs. Accordingly, more attention should be given to suspicious thyroid cancer nodules that show large size, regular shape, and rich blood flow signals on ultrasound to exclude the possibility of PDTCs.

Background: Patients with Alzheimer's disease (AD) manifest progressive decline in writing abilities. Most studies on agraphia in AD have been performed in the alphabetic system, such as English. However, these findings may not be applicable to other written language systems. The unique features of the Chinese written script could affect the patterns of agraphia in Chinese AD patients. The aim of this study was to explore the features of writing errors in Chinese patients with AD and amnestic mild cognitive impairment (a-MCI), as well as to study the relationship between their writing errors and neuropsychological functions. Methods: In this study, we performed an observational study in a group of subjects including 17 AD patients, 14 patients with a-MCI, and 16 elderly healthy controls. We analyzed the writing errors in these subjects and also studied the relationship between their writing errors and neuropsychological functions. Results: Our study showed that in patients whose mother tongue is Chinese, writing ability was comparatively well preserved in the MCI phase but significantly impaired when the disease progressed to the stage of AD. The writing errors showed corresponding increase with the severity of cognition decline, both in the types of errors and rate of occurrence. Analysis of the writing errors showed that word substitution and unintelligible words were the most frequent error types that occurred in all the three study groups. The occurrence rate of unintelligible words was significantly higher in the AD group compared with the a-MCI group (P = 0.024) and control group (P = 0.018). In addition, the occurrence rates of word substitution were also significantly higher in AD (P = 0.013) and a-MCI groups (P = 0.037) than that of control group. However, errors such as totally no response, visuospatial impairment, paragraph agraphia, ideograph, and perseverative writing errors were only seen in AD group. Besides, we also found a high occurrence rate of visuoconstructional errors (13.3%) in our AD group. Conclusions: Our study confirmed that agraphia is an important feature in patients with AD. The writing error profile in patients whose native language is Chinese was unique compared to patients using the alphabetic language system.

With the increasing use of immunosuppressive agents, the number of opportunistic infections has risen in patients with autoimmune diseases. Pneumocystis pneumonia (PCP) is one of these opportunistic infections that have a high mortality rate. However, only a few studies have described PCP in these patients, and these studies are limited in scope. We conducted this retrospective study to describe the clinical characteristics and factors associated with outcomes of PCP in patients with autoimmune diseases.A retrospective study was performed in laboratory diagnosed PCP patients with autoimmune diseases in an academic hospital over a 10-year period. Patients with human immunodeficiency virus (HIV) infection were not included. Clinical characteristics were collected and the factors related to death were analysed.A total of 69 patients with PCP during the study period were included. Common clinical features included fever (81%), cough (56%), and dyspnea (35%). Ground glass opacity (81%) and reticulation (52%) were the most common radiological findings. Concurrent pulmonary infections including bacterium, aspergillus and cytomegalovirus were found in 34% of the patients. The overall in-hospital mortality rate was 32%. High mortality was associated with lower PaO2/FiO2 ratios and albumin levels. The lymphocyte count, CD4+ T cell count, previous usage of immunosuppressive agents, the duration and dose of glucocorticoids did not affect the outcome.The mortality rate in PCP patients with autoimmune diseases is high. Low PaO2/FiO2 ratios and albumin levels are independent prognostic factors of mortality.

Psoriasis is similar to endpoints of epithelial–mesenchymal transition (EMT), a process of epithelial cells transformed into fibroblast-like cells. The molecular epithelial and mesenchymal markers were analysed in psoriatic keratinocytes. No obvious alteration of epithelial markers E-cadherin (E-cad), keratin 10 (K10), K14 and K16 was detected in psoriatic keratinocytes. However, significantly increased expression of Vim, FN, plasminogen activator inhibitor 1 (PAI-1) and Slug was seen. IL-17A and IL-13 at 50 ng ml−1 strongly decreased expression of K10, Vim and FN. TGF-β1 at 50 ng ml−1 promoted the production of N-cad, Vim, FN and PAI-1. Slug was decreased by dexamethasone (Dex), but E-cad was upregulated by Dex. Silencing of ERK partially increased E-cad and K16, but remarkably inhibited K14, FN, Vim, β-catenin, Slug and α5 integrin. Moreover, inhibition of Rho and GSK3 by their inhibitors Y27632 and SB216763, respectively, strongly raised E-cad, β-catenin and Slug. Dex decreased Y27632-mediated increase of β-catenin. Dex at 2.0 µM inhibited SB216763-regulated E-cad, β-catenin and slug. In conclusion, EMT in psoriatic keratinocytes may be defined as an intermediate phenotype of type 2 EMT. ERK, Rho and GSK3 play active roles in the process of EMT in psoriatic keratinocytes.

Introduction: Systemic sclerosis is a complex disease characterized by the fibrosis and vasculopathy. Aim: We aimed to assess scleroderma by examining involucrin, an early terminal differentiation marker of epidermal keratinocytes. Material and methods: Immunolocalization of involucrin was performed in healthy controls and patients with scleroderma lesions by using an immunofluorescence (IF) assay. Normal and scleroderma keratinocytes were incubated in low-Ca basal-defined K-SFM overnight. Cells were pre-treated with Y-27632 (a Rho signalling pathway inhibitor) or interleukins (ILs), tumor necrosis factor-α (TNF-α), transforming growth factor β1 (TGF-β1), endothelin-1 (ET-1), interferon-γ (IFN)-γ, vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) - BB. The involucrin protein expression level was measured by western blot. Results: Compared with the normal skin, involucrin was detected in the granular layer and the upper stratum spinosum in patients with scleroderma lesions. However, involucrin protein expression was decreased in cultured scleroderma keratinocytes. IL-6, IL-10, IL-17A, TNF-α, TGF-β1, ET-1, IFN-γ, VEGF165, and PDGF-BB increased involucrin expression in normal keratinocytes but decreased it in scleroderma keratinocytes. IFN-γ and IL-13 remarkably downregulated involucrin levels in normal and scleroderma keratinocytes, respectively, by Y-27632 intervention. Conclusions: Inflammatory cytokines, such as IL-6, IL-10, TGF-β1, ET-1, IFN-γ, VEGF, PDGF-BB, and Rho signalling pathway may be associated with the delayed epidermal differentiation in scleroderma. [ABSTRACT FROM AUTHOR]