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Rationale and Objectives The direct damage caused by ischemic stroke is relatively localized, but structural reorganization of cortical regions could occur across the brain. Changes of large-scale, cortical structural brain networks after basal ganglia stroke are less well reported. We, therefore, aim to explore the abnormalities of cortical morphology and structural network topology in patients with unilateral basal ganglia stroke during the subacute period. Materials and Methods Thirty patients with first-ever basal ganglia stroke and thirty age- and sex-matched healthy controls were recruited for our analysis. Patients underwent structural magnetic resonance imaging examinations and clinical assessment from seven days to three months post-stroke. Alterations in cortical morphology and topological properties of the cortical structural network were measured respectively using the surface-based morphology and graph-theoretical methods. Results We observed focal cortical atrophy, specifically in areas of frontal and temporal cortices. Moreover, the cortical thickness in the contralesional transverse temporal gyrus and superior temporal gyrus was positively correlated with cognitive function scores. Network analysis revealed that patients with basal ganglia stroke showed increased clustering coefficient, increased mean local efficiency as well as a reorganization of degree-based hubs. In addition, these patients also showed reduced robustness under a random attack compared to healthy controls. Conclusion These findings indicated a unique pattern of cortical reorganization and the abnormal topological organization of cortical thickness-based structural covariance networks in patients with basal ganglia stroke, which is beneficial to understand the pathophysiological mechanisms of functional disorders at the cortical structural network level and find potential targets for induced neuromodulation.

BACKGROUND AND AIMS Globally, NAFLD is one of the most common liver disorders, with an estimated prevalence rate of more than 30% in men and 15% in women and an even higher prevalence in people with type 2 diabetes mellitus. Optimal pharmacologic therapeutic approaches for NAFLD are an urgent necessity. APPROACH AND RESULTS In this study, we showed that compared with healthy controls, hepatic ACSL4 levels in patients with NAFLD were found to be elevated. Suppression of ACSL4 expression promoted mitochondrial respiration, thereby enhancing the capacity of hepatocytes to mediate β-oxidation of fatty acids and to minimize lipid accumulation by up-regulating peroxisome proliferator-activated receptor coactivator-1 alpha. Moreover, we found that abemaciclib is a potent and selective ACSL4 inhibitor, and low dose of abemaciclib significantly ameliorated most of the NAFLD symptoms in multiple NAFLD mice models. CONCLUSIONS Therefore, inhibition of ACSL4 is a potential alternative therapeutic approach for NAFLD.

BACKGROUND: The non-invasive characterization of glioma metabolites would greatly assist the management of glioma patients in the clinical setting. This study investigated the applicability of intra-subject inter-metabolite correlation analyses for differentiating glioma malignancy and proliferation. METHODS: A total of 17 negative controls (NCs), 39 low-grade gliomas (LGGs) patients, and 25 high-grade gliomas (HGGs) subjects were included in this retrospective study. Amide proton transfer (APT) and magnetization transfer contrast (MTC) imaging contrasts, as well as total choline/total creatine (tCho/tCr) and total N-acetylaspartate/total creatine (tNAA/tCr) ratios quantified from magnetic resonance spectroscopic imaging (MRSI) were co-registered voxel-wise and used to produce three intra-subject inter-metabolite correlation coefficients (IMCCs), namely, R(APT) (vs)(. MTC), R(APT) (vs)(. tCho/tCr), and R(MTC) (vs)(. tNAA/tCr). The correlation between the IMCCs and tumor grade and Ki-67 labeling index (LI) for tumor proliferation were explored. The differences in the IMCCs between the three groups were compared with one-way analysis of variance (ANOVA). Finally, regression analysis was used to build a combined model with multiple IMCCs to improve the diagnostic performance for tumor grades based on receiver operator characteristic curves. RESULTS: Compared with the NCs, gliomas showed stronger inter-metabolic correlations. R(APT) (vs)(. MTC) was significantly different among the three groups (NC vs. LGGs vs. HGGs: −0.18±0.38 vs. −0.40±0.34 vs. −0.70±0.29, P

Metastatic brain tumors are the rare cause of intracerebral hemorrhage in the young. In this study, we present a case of a 24-year-old woman who suffered from brain and lung metastatic choriocarcinoma with intracerebral hemorrhage as initial presentation. Head computed tomography showed an irregular hematoma of the right frontal lobe and enlarged within 1 month. Chest X ray showed a mass in the right lung. This patient responded well with combined treatment with craniotomy for evacuation of hematoma, multidrug chemotherapy and lobectomy. This case report discusses a rare phenomenon of hemorrhage metastasis in the brain from choriocarcinoma. The better knowledge of this entity would facilitate earlier diagnosis and improve the outcome.

Purpose Anti‐CD19 chimeric antigen receptor T (CAR‐T) cell therapy has demonstrated remarkable efficacy for refractory and relapsed diffuse large B cell lymphoma (R/R DLBCL). However, this therapy failed in nearly 25% patients mainly due to antigen loss. The authors performed a phase Ⅱ trial by coadministration of anti‐CD19 and anti‐CD20 CAR‐T cells treatment for R/R DLBCL and evaluated its efficacy and toxicity. Methods Totally 21 patients with DLBCL were enrolled in this study. The patients were conditioned with fludarabine and cyclophosphamide before the infusion of anti‐CD19 and anti‐CD20 CAR‐T cells. Treatment response, toxicity, and persistence were monitored continuously. Results Of the 21 patients received the treatment, the objective response rate (ORR) is 81.0% (95% confidence interval [CI], 58.1%‐94.6%) with four cases of bulk (4/5) and one case of testis involvement; 52.4% (95% CI, 29.8%‐74.3%) had a complete response (CR). Peak levels of anti‐CD19 and anti‐CD20 CAR cells were associated with response (P = .007 and .002). Grade 3‐4 cytokine release syndrome (CRS) and neurologic events occurred in 28.5% and 9.5% patients, respectively. Median overall survival (OS) and progression‐free survival (PFS) were 8.1 and 5.0 months, respectively. The maximum standard uptake value (SUVmax) of CD4/CD8 ratio before and after infusion were associated with responses, and the total lesion glycolysis (TLG) before infusion correlates with cytokines level. Conclusions Coadministration of anti‐CD19 and CD20 CAR‐T cells therapy for DLBCL is feasible with manageable toxicity. Cytokine markers are related to toxicity and SUVmax could predict efficacy. This trial was registered at www.clinicaltrials.gov as NCT03207178., In this study, we confirmed that combination of anti‐CD19 and anti‐CD20 CAR‐T cells therapy strategy was efficient (81% ORR and 52.4% CR respectively) for R/R DLBCL, and that the toxicities was transient and manageable. To our knowledge, this is the first report that combination of anti‐CD19 and anti‐CD20 double‐target CAR‐T cell therapy for R/R DLBCL, and our data demonstrated the feasibility of combination of anti‐CD19 and anti‐CD20 CAR‐T cells therapy for R/R DLBCL.

Background Talaromyces marneffei (TM) is a dimorphic fungus mainly prevalent in Southeast Asian countries, which often causes disseminated life-threatening infection. TM infection often occurs in HIV/AIDS patients even in the antiretroviral therapy (ART) era. However, there has as yet, not been a systematic analysis of the prevalence of TM infection in HIV-infected populations in Asia. Methods In this study, we searched Pubmed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and WanFang from inception to 21 November 2018 for studies reporting TM infection in people living with HIV/AIDS (PLWHA). Our meta-analysis included studies investigating the prevalence of TM infection in PLWHA. Reviews, duplicate studies, and animal studies were excluded. A random effects model was used to estimate pooled prevalence, and meta-regression analysis was conducted to explore potential factors for heterogeneity. Results 159,064 patients with HIV infection in 33 eligible studies were included in our meta-analysis. The pooled prevalence of TM infection in PLWHA was 3.6%. Vietnam had the highest prevalence (6.4%), followed by Thailand (3.9%), China (3.3%), India (3.2%) and Malaysia (2.1%). In China, TM infection was most prevalent in South China (15.0%), while the burden in Southwest China was not very heavy (0.3%). CD4+ T-cell counts below 200 cells/mm3 contributed to the increased risk of TM infection in PLWHA (OR 12.68, 95%CI: 9.58–16.77). However, access to ART did not significantly decrease the risk of TM infection in PLWHA. Conclusions The burden of TM infection in Asia is heavy, and varies from region to region. PLWHA in lower latitude areas are more likely to suffer from TM infection. Optimization of diagnostic tools and universal screening for TM in vulnerable people to ensure early case detection and prompt antifungal treatment should be considered.

Purpose This study aims to report the clinical features of an infant with CGL in a Chinese Zhuang ethnic family, whose family members were discovered to carry new pathogenic mutations in the BSCL2. Patients and methods In this study, we report clinical and molecular investigations of CGL disease in a family of 4 members (parents and two sons). We used whole exome sequencing (WES) in the family to examine the genetic cause of the disease. Results The proband presented with skin pigmentation, hypertriglyceridemia and diabetes. WES identified a previously unreported compound heterozygous mutation in the BSCL2 (c.545_546insCCG heterozygous mutation and exon 3 heterozygous deletion) in the proband. His mother is a heterozygous carrier of the c.545_546insCCG mutation and his father and brother are carriers of the exon 3 heterozygous deletion. Conclusion Compound heterozygous mutation of the BSCL2 (new c.545_546insCCG heterozygous mutation and new exon 3 heterozygous deletion) was detected in the proband with characteristic clinical manifestations of CGL2.

Xuan Zhang, Yuan-yuan Qin, Min Chen, Yang-yang Wu, Fa-quan Lin Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, People’s Republic of ChinaCorrespondence: Fa-quan LinDepartment of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, No.6 Shuang Yong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, People’s Republic of ChinaTel +86 13877118318Email fqlin1998@163.comPurpose: For the diagnosis of nasopharyngeal carcinoma (NPC), reliable early indicators with sensitivity and specificity should be sought. This study evaluated the effect of the combined use of mean platelet volume/platelet count ratio (MPV/PC ratio) and platelet distribution width (PDW) for differential diagnosis of NPC. In this study, MPV/PC ratio was used for the first time to diagnostically evaluate NPC.Patients and methods: We retrospectively analyzed various hematological indices of three subject groups (208, 185, and 162 patients with NPC, benign tumors of the nasopharynx, and healthy subjects, respectively) and evaluated the value of combined use of MPV/PC ratio and PDW for differential diagnosis of the three groups using the one-way analysis of variance.Results: Comparison of laboratory variables between the three groups showed a significant difference in MPV/PC ratio and PDW (P

PurposeThis study aimed to assess the spatiotemporal evolution of oxygen extraction fraction (OEF) in ischemic stroke with a newly developed cluster analysis of time evolution (CAT) for a combined quantitative susceptibility mapping and quantitative blood oxygen level-dependent model (QSM + qBOLD, QQ).MethodOne hundred and fifteen patients in different ischemic stroke phases were retrospectively collected for measurement of OEF of the infarcted area defined on diffusion-weighted imaging (DWI). Clinical severity was assessed using the National Institutes of Health Stroke Scale (NIHSS). Of the 115 patients, 11 underwent two longitudinal MRI scans, namely, three-dimensional (3D) multi-echo gradient recalled echo (mGRE) and 3D pseudo-continuous arterial spin labeling (pCASL), to evaluate the reversal region (RR) of the initial diffusion lesion (IDL) that did not overlap with the final infarct (FI). The temporal evolution of OEF and the cerebral blood flow (CBF) in the IDL, the RR, and the FI were assessed.ResultsCompared to the contralateral mirror area, the OEF of the infarcted region was decreased regardless of stroke phases (p < 0.05) and showed a declining tendency from the acute to the chronic phase (p = 0.022). Five of the 11 patients with longitudinal scans showed reversal of the IDL. Relative oxygen extraction fraction (rOEF, compared to the contralateral mirror area) of the RR increased from the first to the second MRI (p = 0.044). CBF was about 1.5-fold higher in the IDL than in the contralateral mirror area in the first MRI. Two patients showed penumbra according to the enlarged FI volume. The rOEF of the penumbra fluctuated around 1.0 at earlier scan times and then decreased, while the CBF decreased continuously.ConclusionThe spatiotemporal evolution of OEF and perfusion in ischemic lesions is heterogeneous, and the CAT-based QQ method is feasible to capture cerebral oxygen metabolic information.

Current WHO guidelines (2018) recommend screening for cryptococcal antigen (CrAg) in HIV-infected persons with CD4+ T cell counts

Background Follow-up study of coronavirus disease 2019 (COVID-19) survivors has rarely been reported. We aimed to investigate longitudinal changes in the characteristics of COVID-19 survivors after discharge. Methods A total of 594 COVID-19 survivors discharged from Tongji Hospital in Wuhan from February 10 to April 30, 2020 were included and followed up until May 17, 2021. Laboratory and radiological findings, pulmonary function tests, electrocardiogram, symptoms and signs were analyzed. Results 257 (51.2%) patients had at least one symptom at 3 months post-discharge, which decreased to 169 (40.0%) and 138 (28.4%) at 6-month and 12-month visit respectively. During follow-up period, insomnia, chest tightness, and fatigue were the most prevalent symptoms. Most laboratory parameters returned to normal, whereas increased incidence of abnormal liver and renal function and cardiovascular injury was evidenced after discharge. Fibrous stripes (213; 42.4%), pleural thickening and adhesions (188; 37.5%) and enlarged lymph nodes (120; 23.9%) were the most common radiographical findings at 3 months post-discharge. The abnormalities of pulmonary function included obstructive, restrictive, and mixed, which were 5.5%, 4.0%, 0.9% at 6 months post, and 1.9%, 4.7%, 0.2% at 12 months. Electrocardiogram abnormalities occurred in 256 (51.0%) patients at 3 months post-discharge, including arrhythmia, ST-T change and conduction block, which increased to 258 (61.1%) cases at 6-month visit and were maintained at high frequency (242;49.8%) at 12-month visit. Conclusions Physiological, laboratory, radiological, or electrocardiogram abnormalities, particularly those related to renal, cardiovascular, and liver functions are common in patients who recovered from coronavirus disease 2019 (COVID-19) up to 12 months post-discharge.

Statins are a commonly prescribed cardiovascular disease drug class that can increase risk of type 2 diabetes (T2D). To investigate molecular mechanisms underlying this effect, we created induced pluripotent stem cells (iPSCs) from normoglycemic patients identified from electronic health records of Kaiser Permanente of Northern California who developed T2D after statin initiation or controls who maintained normal fasting glucose on statin treatment (24 per group). RNAseq analysis of iPSCs incubated with 250nM atorvastatin, 500nM simvastatin or mock buffer for 24h identified MIR194-2HG as one of the transcripts exhibiting the greatest differential change between cases vs. controls. Both statins increased MIR194-2HG in the controls but decreased levels in cases. This long non-coding RNA encompasses two microRNAs: MIR-192 and MIR-194. MIR192-5p is predicted to bind the 3’ UTR of the glucagon like peptide 1 receptor gene (GLP1R), and we found that transfection of a rat insulinoma cell line (INS-1) with a MIR192-5p mimic caused increased Glp1r transcript (1.4-fold) and protein (2.1-fold) levels compared to a scrambled control. Using a luciferase reporter containing human GLP1R 3’ UTR, we observed similar increases in signal; however, this elevation remained even after disruption of the predicted MIR192-5p binding site demonstrating that MIR192-5p upregulates GLP1R through an indirect mechanism. GLP1R augments glucose-stimulated insulin secretion, and we found that the MIR192-5p mimic increased insulin levels in media of glucose-stimulated INS-1 cells (1.4-fold). Reduction in media insulin in INS-1 cells treated with 1 μM simvastatin was rescued by MIR192-5p overexpression, while a MIR192-5p antisense inhibitor abolished this effect. These findings implicate MIR192-5p in statin-induced impairment of glucose stimulated insulin secretion through the regulation of GLP1R, an effect that may contribute to the increased risk of T2D in statin users. Disclosure Y. Kuang: None. M. W. Medina: None. A. Munoz: None. Y. Qin: None. A. Dosé: None. G. Nalula: None. E. Theusch: None. G. Sanchez: None. C. Iribarren: None. R. M. Krauss: Advisory Panel; Self; Virta Health Corp. Funding National Institutes of Health (P50GM115318)

BACKGROUND Previous studies have found widespread impairment of white matter (WM) integrity and disruption of structural network connectivity in cerebral small-vessel disease, but have not evaluated these changes jointly in nondemented patients. PURPOSE To jointly investigate the microstructural impairment of WM and the related alterations of structural network topology in nondemented cerebral small-vessel disease (CSVD-ND). STUDY TYPE Prospective. POPULATION Thirty-seven CSVD-ND patients and 34 elderly controls, who were age-, sex-, and education-matched. FIELD STRENGTH/SEQUENCE 3.0T/diffusion tensor imaging (DTI). ASSESSMENT Clinical characteristics, lacunar infarct, and white matter hyperintensity (WMH) was assessed. A multiatlas likelihood fusion (MALF) algorithm was used for DTI-based brain segmentation and network node defining. Then the alterations of WM integrity and structural network topology were investigated jointly. STATISTICAL TESTS Student's t-test, chi-square test, Mann-Whitney U-test, linear regression, Pearson correlation, and multiple comparison correction. RESULTS Decreased fractional anisotropy and increased trace values were observed in predefined structures (P < 0.05, familywise error rate-corrected), including major commissural fibers, projection fibers, and some association fibers. Topologically, both groups showed small-worldness. CSVD-ND patients showed reduced global and local efficiency (P < 0.001). Despite widespread impairment of WM integrity, CSVD-ND patients only showed reduced nodal efficiency in the right superior occipital gyrus and the right lingual gyrus (P < 0.05, familywise error rate-corrected). The nodal local efficiency of the right precuneus was associated with the processing speed after adjusting the effect of lacunar infarct and WMH (r = -0.499, P = 0.038). DATA CONCLUSION WM integrity was widely impaired in nondemented CSVD patients but structural network connectivity was relatively preserved. DTI may potentially provide information for the pathophysiology of CSVD in the nondemented phase. LEVEL OF EVIDENCE 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:1162-1169.

Breast cancer has the highest incidence among cancers and is the most frequent cause of death in women worldwide. The detailed mechanism of the pathogenesis of breast cancer has not been fully elucidated, and there remains a lack of effective treatment methods for the disease. SUMOylation covalently conjugates a large amount of cellular proteins, and affects their cellular localization and biological activity to participate in numerous cellular processes. SUMOylation is an important process and imbalance of SUMOylation results in the progression of human diseases. Increasing evidence shows that numerous SUMOylated proteins are involved in the occurrence and development of breast cancer. This review summarizes a series of studies on protein SUMOylation in breast cancer in recent years. The study of SUMOylated proteins provides a comprehensive understanding of the pathophysiology of breast cancer and provides evolving therapeutic strategies for the treatment of breast cancer.

Vascular endothelial growth factor affects the invasiveness of solid tumors by regulating angiogenesis. However, it is not clear whether VEGF could be used to predict the prognosis of DLBCL in the era of rituximab-based immunotherapy. We conducted a retrospective study to explore response to therapy and the prognostic value of VEGF on DLBCL in the rituximab era. The subjects were 65 patients with a histological diagnosis of DLBCL from the Affiliated Hospital of Xuzhou Medical University. Kaplan-Meier analysis was performed to estimate the cumulative survival rate of patients with different VEGF and IPI levels, and comparisons between groups were made using the log-rank test. DLBCL patients with elevated VEGF were more likely to have extranodal involvement, advanced stage, Myc/Bcl-2 double expression, and a higher Ki-67 score. Elevated VEGF was associated with poor therapeutic response and survival. When patients were divided into low, low-intermediate, high-intermediate and high-risk groups using the V-IPI model based on VEGF and IPI, PFS rates were 94.4, 74.1, 40.6 and 14.8%, respectively. This model better identified low-risk patients than IPI (85.9, 88.9, 37 and 7.8%). Our results demonstrate that VEGF predicts therapeutic response in DLBCL and the V-IPI model accurately predicts PFS of low-risk DLBCL in the rituximab era.

The coronavirus disease 2019 (COVID-19) rapidly progressed to a global pandemic. Although patients totally recover from COVID-19 pneumonia, long-term effects on the brain still need to be explored. Here, two subtypes (mild type-MG and severe type-SG) with no specific neurological manifestations at the acute stage and no obvious lesions on the conventional MRI three months after discharge were recruited. Changes in gray matter morphometry, cerebral blood flow (CBF) and white matter (WM) microstructure were investigated using MRI. The relationship between brain imaging measurements and inflammation markers were further analyzed. Compared with healthy controls, the decrease in cortical thickness/CBF, and the changes in WM microstructure were observed to be more severe in the SG than MG, especially in the frontal and limbic systems. Furthermore, changes in brain microstructure, CBF and tracts parameters were significantly correlated with inflammatory markers. The indirect injury related to inflammatory storm may damage the brain, that led to these interesting observations. There are also other likely potential causes, such as hypoxemia and dysfunction of vascular endothelium, et al. The abnormalities in these brain areas need to be monitored in the process of complete recovery, which could help clinicians to understand the potential neurological sequelae of COVID-19.\ud \ud Key words: COVID-19; Brain MRI; Recovered patients; Inflammatory markers; Cortical thickness; Cerebral blood flow; microstructure; gray matter; white matter; subcortical nuclei

A modeling and simulation method for wireless sensor network (WSN) using discrete event system specification (DEVS) is proposed in this paper considering that the existing simulators cannot fully satisfy the requirements of WSN simulation. The method is for multi-layer and multi-aspect modeling which contains the component layer in sensor nodes, the sensor node layer, the wireless sensor net-work layer and the external environment where a WSN is exposed, and modules in lower layer are integrated into superior models through coupling relation and model reuse. Minimum Hop Count (MHC) protocol is chosen as the routing protocol of the WSN in the simulation experiment. It is finally demonstrated through the performance analysis of WSN using MHC that the proposed DEVS-based modeling and simulation method is feasible for WSN simulation.

Qin, Y.Y., 2020. Cloud storage data retrieval method of port logistic based on particle swarm optimization. In: Al-Tarawneh, O. and Megahed, A. (eds.), Recent Developments of Port, Marine, and Ocean Engineering. Journal of Coastal Research, Special Issue No. 110, pp. 295–298. Coconut Creek (Florida), ISSN 0749-0208.The arrival of big data is a major challenge for information technology. In particular, cloud storage and retrieval of big data is also an important technology. It is also an important part of national information security. The cloud storage data retrieval method of port logistic based on particle swarm optimization algorithm proposed in this paper, combined with Matlab software, realizes the PSO algorithm optimization model, and establishes an experimental scenario to simulate the retrieval process of cloud storage. The results prove that the data retrieval method of port logistic has a high retrieval speed and stability. In the future research, the author will focus on the experimental improvement of the method of port logistic to obtain better application effect in the data retrieval process of cloud storage.

Aims Our object was to find the most appropriate, most effective, and most readily available of four induction regimens for HIV-associated cryptococcal meningitis (CM) (Regimen A: 1 week of AmB plus 5-FC followed by 1 week of fluconazole, Regimen B: 1 week of AmB plus fluconazole followed by 1 week of fluconazole, Regimen C: 2 weeks of AmB plus 5-FC, Regimen D: 2 weeks of AmB plus fluconazole), given the vast differences between resource-limited and resource-abundant settings regarding therapeutic drug accessibility, availability, and affordability for HIV-associated (CM). Methods We conducted a network meta-analysis to compare the therapeutic efficacy and safety of four different induction treatment regimens. Results The 10-week mortality of Regimen A was significantly lower than that of Regimen B and D, and the 2-week mortality of Regimen A was significantly lower than that of Regimen B. Furthermore, there were no statistically significant differences in 10-week mortality, 2-week mortality, as well as in effective fungicidal activity (EFA) over the first 2 weeks among Regimens B, C, and D. The statistical differences in adverse events between Regimen B and Regimen D, and Regimen C and Regimen D were not calculated to be significant. Conclusions Our results indicate that, 1 week of AmB plus 5-FC followed by 1 week of fluconazole is superior to the three other studied regimens, and that when 5-FC is not available, accessible, or affordable, 2 weeks of AmB plus fluconazole or 1 week of AmB plus fluconazole followed by 1 week of fluconazole is an appropriate substitution for 2 weeks of AmB plus 5-FC.

Abnormal structural connectivity of cerebral small-vessel disease (CSVD) is associated with cognitive impairment. But the different characteristics of structural connectivity have not been elucidated in early CSVD patients. The current study aimed to investigate the potential differences of structural connectivity in CSVD patients with mild cognitive impairment (MCI) and CSVD patients with normal cognition. Twenty-two CSVD patients with MCI, 34 CSVD patients with normal cognition, and 35 controls, who were age, sex, and education matched underwent diffusion tensor imaging and high resolution T1-weighted imaging. Clinical characteristics, lacunar infarct volume, white matter hyperintensity (WMH) volume, and global atrophy were quantitatively evaluated. Maps of fiber connectivity density (FiCD) were constructed and compared across groups in vertex levels. Pearson correlation was used to estimate the imaging–clinical relationships with control of general characteristics. CSVD patients with MCI had higher lesion load of WMH and lacunar infarcts, and correspondingly lower global FiCD value than CSVD patients with normal cognition (P < 0.01). Lacunar infarct (r = −0.318, P < 0.01) and WMH (r = −0.400, P < 0.01), but not global atrophy, age, or sex, were significantly correlated with the global FiCD value. CSVD patients with normal cognition showed decreased FiCD value mainly in the prefrontal areas (P < 0.01 with Monte Carlo correction). Compared with CSVD patients with normal cognition, CSVD patients with MCI showed significantly decreased FiCD value in enlarged frontal and parietal areas (P < 0.01 with Monte Carlo correction). Inter-group comparisons showed regional enhanced impairment of connectivity density in CSVD patients with MCI in the left superior frontal gyrus, the left precuneus, and the orbital part of the right inferior frontal gyrus (P < 0.01 with Monte Carlo correction). Regional FiCD value of frontal and parietal areas was associated with the cognitive function (P < 0.01). In conclusion, cognitively normal CSVD patients already have disruptions of structural connectivity. The extent and intensity of connectivity disruptions in frontal and parietal areas may underlie the mechanism of cognitive impairment in CSVD. Fiber connectivity density measurements may be helpful for quantitative description of structural cortical connectivity.

CCL20, as a chemokine, plays an important role in rheumatoid arthritis, psoriasis, and other diseases by binding to its receptor CCR6. Recent 10 years' research has demonstrated that CCL20 also contributes to the progression of many cancers, such as liver cancer, colon cancer, breast cancer, pancreatic cancer, and gastric cancer. This article reviews and discusses the previous studies on CCL20 roles in cancers from the aspects of its specific effects on various cancers, its remodeling on tumor microenvironment (TME), its synergistic effects with other cytokines in tumor microenvironment, and the specific mechanisms of CCL20 signal activation, illustrating CCL20 signaling in TME from multiple directions.

To explore the feasibility and diagnostic performance of radiomics based on anatomical, diffusion and perfusion MRI in differentiating among glioma subtypes and predicting tumour proliferation. 220 pathology-confirmed gliomas and ten contrasts were included in the retrospective analysis. After being registered to T2FLAIR images and resampling to 1 mm3 isotropically, 431 radiomics features were extracted from each contrast map within a semi-automatic defined tumour volume. For single-contrast and the combination of all contrasts, correlations between the radiomics features and pathological biomarkers were revealed by partial correlation analysis, and multivariate models were built to identify the best predictive models with adjusted 0.632+ bootstrap AUC. In univariate analysis, both non-wavelet and wavelet radiomics features were correlated significantly with tumour grade and the Ki-67 labelling index. The max R was 0.557 (p = 2.04E-14) in T1C for tumour grade and 0.395 (p = 2.33E-07) in ADC for Ki-67. In the multivariate analysis, the combination of all-contrast radiomics features had the highest AUCs in both differentiating among glioma subtypes and predicting proliferation compared with those in single-contrast images. For low-/high-grade gliomas, the best AUC was 0.911. In differentiating among glioma subtypes, the best AUC was 0.896 for grades II–III, 0.997 for grades II–IV, and 0.881 for grades III–IV. In predicting proliferation levels, multicontrast features led to an AUC of 0.936. Multicontrast radiomics supplies complementary information on both geometric characters and molecular biological traits, which correlated significantly with tumour grade and proliferation. Combining all-contrast radiomics models might precisely predict glioma biological behaviour, which may be attributed to presurgical personal diagnosis. • Multicontrast MRI radiomics features are significantly correlated with tumour grade and Ki-67 LI. • Multimodality MRI provides independent but supplemental information in assessing glioma pathological behaviour. • Combined multicontrast MRI radiomics can precisely predict glioma subtypes and proliferation levels.

Background Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) has become an important disease of hospitalized elderly patients, which lack simple and inexpensive indicators for evaluating the condition and prognosis. This study was performed to investigate the clinical significance of the serum albumin/globulin ratio (AGR) in elderly patients with AECOPD. Methods The data of 252 hospitalized elderly patients with AECOPD, 89 stable COPD patients and 115 elderly healthy individuals were analyzed and compared. The differences in the AGR, logarithm of the serum C-reactive protein (LogCRP) level, prealbumin (PA) level, and immunoglobulin G (IgG) level were compared. AECOPD patients were grouped using the optimal cutoff values of each index to compare the difference in the combined infection rate. The correlation between hospital stays and AGR was analyzed. Results The AGR, LogCRP, PA level, and IgG level were different among the AECOPD group, stable COPD group and healthy control groups (P

Background/Aims: Thiamine-responsive megaloblastic anemia syndrome is a rare autosomal recessive disorder resulting from mutations in SLC19A2, and is mainly characterized by megaloblastic anemia, diabetes, and progressive sensorineural hearing loss. Methods: We study a Chinese Zhuang ethnicity family with thiamine-responsive megaloblastic anemia. The proband of the study presented with anemia and diabetes, similar to his late brother, as well as visual impairment. All clinical manifestations were corrected with thiamine (30 mg/d) supplementation for 1–3 months, except for visual impairment, which was irreversible. The presence of mutations in all exons and the flanking sequences of the SLC19A2 gene were analyzed in this family based on the proband’s and his brother’s clinical data. Computer analysis and prediction of the protein conformation of mutant THTR-1. The relative concentration of thiamine pyrophosphate in the proband’s whole blood before and after initiation of thiamine supplement was measured by high performance liquid chromatography (HPLC). Results: Gene sequencing showed a homozygous mutation in exon 6 of the SLC19A2 gene (c.1409insT) in the proband. His parents and sister were diagnosed as heterozygous carriers of the c.1409insT mutation. Computer simulation showed that the mutations caused a change in protein conformation. HPLC results suggested that the relative concentration of thiamine pyrophosphate in the proband’s whole blood after thiamine supplement was significantly different (P=0.016) from that at baseline. Conclusions: This novel homozygous mutation (c.1409insT) caused the onset of thiamine-responsive megaloblastic anemia in the proband.

To investigate the value of neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR) and carcinoembryonic antigen (CEA), alone or in combination, in diagnosing gastric cancer (GC), we retrospectively analyzed a cohort of 201 patients with GC, 161 patients with benign gastric lesions, and 157 healthy subjects. We obtained routine blood indices and CEA levels to evaluate the diagnostic value of NLR, PLR and CEA for GC, based on receiver operating characteristic (ROC) curves. We found that serum NLR, PLR and CEA in the GC group were significantly higher than those in the benign lesion group (PNLR

Purpose To assess the region-specific atrophy of precentral gyrus (PrCG) and its correlation to clinical function score in amyotrophic lateral sclerosis (ALS). Materials and Methods Twenty-eight patients with sporadic ALS and 28 healthy controls underwent high-resolution 3D T1-BRAVO magnetic resonance imaging at 3T. The bilateral PrCG segmentations were automatically obtained from a validated segmentation pipeline based on diffeomorphic multi-atlas likelihood fusion. Patients with ALS were further subclassified into early-stage (ALS-e, n = 22) and late-stage (ALS-l, n = 6) groups, with 12 months as a disease duration cutoff. Vertex-based shape analysis was performed to quantify the region-specific abnormalities of PrCG in ALS subgroups as compared to controls. In addition, we tested the statistical association between altered PrCG morphometry and clinical disability in ALS as evaluated by the revised ALS Functional Rating Scale (ALSFRS-r). Results Compared to controls, vertex-wise analysis showed that both ALS-e and ALS-l had significant atrophy of the dorsal-lateral part of PrCG (P

We proposed and validated a fully-automated classification procedure for amyotrophic lateral sclerosis (ALS) using structural magnetic resonance imaging; specifically, T1-weighted images from 28 ALS subjects and 28 healthy control (HC) subjects were used. The raw features were obtained from a validated multi-granularity whole-brain analysis pipeline, providing multi-level whole-brain segmentation volumes. We employed the support vector machine as our classification algorithm with several feature selection techniques analyzed. According to our leave-one-out cross validation experiment results, the whole-brain structural volumes from Level 4, followed by a feature selection utilizing the standardized Wilcoxon two-sample rank sum statistic, yielded the best classification performance; overall accuracy: 83.93%, sensitivity: 85.71%, specificity: 82.14%, and the area under the receiver operating characteristic curve: 0.8380. The feature selection procedure revealed that the volumes of the thalamus, especially that on the left hemisphere, are the most important (of highest ranking) in the ALS-vs-HC discrimination.

Background: Current WHO guidelines (2018) recommend screening for cryptococcal antigen (CrAg) in HIV+ persons with CD4

Background Current WHO guidelines (2018) recommend screening for cryptococcal antigen (CrAg) in HIV-infected persons with CD4+ T cell counts Method We conducted a meta-analysis using data extracted from randomized controlled studies (RCTs) and cohort studies found in a search of Pubmed, Web of Science, the Cochrane Library and the EMBASE/MEDLINE database. Results The pooled prevalence of CrAg positivity in HIV-infected persons with CD4+ T cell countsp Conclusions In our meta-analysis the incidence of CM was significantly reduced by pre-emptive antifungal therapy in CrAg+ HIV-infected persons with CD4

Background Mean platelet volume (MPV) is a marker of platelet activation. MPV and platelet count (PC) are negatively correlated, and their ratio (MPV/PC) is informative for the diagnosis of malignant tumors. However, the relationship between MPV/PC and colorectal cancer is unclear. This retrospective clinical study aimed to evaluate the diagnostic value of MPV/PC in colorectal cancer. Methods Hematological examinations were performed at initial diagnosis in patients with colorectal cancer (n = 186) or adenomatous polyp (n = 132) and healthy controls (n = 108). Hematological parameters evaluated included white blood cells, red blood cells, hemoglobin, neutrophils, lymphocytes, monocytes, PC, and MPV. Statistical analyses included Student’s t-test, one-way ANOVA or Kruskal-Wallis H test, chi-square tests, Spearman’s correlation test and receiver operating characteristic (ROC). ROC curve was used to evaluate the diagnostic values of MPV and MPV/PC in colorectal cancer. Results Among these groups, MPV was significantly lower in colorectal cancer than in adenomatous polyp (p = 0.002) and healthy controls (p

To characterize brown adipose tissue (BAT) in polycystic ovary syndrome (PCOS) patients in comparison to healthy subjects using Z-spectral imaging (ZSI).ZSI data were collected on 19 normal control females (NCF), 17 males (NCM), and 13 PCOS patients. By fitting to multiple Lorentzian functions, ZSI provides fat-water fraction (FWF) of tissue in the supraclavicular area that can be used to differentiate between white adipose tissue (WAT), BAT, and muscle. The fraction of BAT over the total fat depot (BATf) and the average FWF in BAT or FWF(BAT) were then computed, reflecting relative BAT mass and BAT metabolism respectively. The parameters were compared among the three groups, and the correlations to Body Mass Index (BMI) were also quantified.There was an inverse correlation between BATf and BMI in normal subjects. The BATf of the PCOS group was significantly smaller than the NCF (P 0.001). On the other hand, FWF(BAT) correlated linearly with BMI in healthy subjects. The PCOS group had higher FWF(BAT) than the NCF group (P 0.001).Normal subjects with higher BMI show less BATf and have increased FWF(BAT), indicating relatively higher level of metabolic passive WAT depot and relatively reduced metabolism in their BAT depots. PCOS patients have the least BATf and the highest FWF(BAT), suggesting decreased BAT mass and function in PCOS. Novel imaging technique with ZSI for the characterization of BAT mass and function in PCOS may help to monitor treatment responses of PCOS therapies.

Various studies report discordant results regarding the efficacy, parameters, and underlying mechanisms of repetitive transcranial magnetic stimulation (rTMS) combined with cognitive training (CT) on Alzheimer’s disease (AD). The objective of the study was to assess the effect of rTMS-CT on cognition, the activities of daily life, neuropsychiatric behavioral symptoms, and metabolite levels beneath the stimulated areas of the brain in patients with AD and to investigate the correlation of metabolic changes (measured with proton magnetic resonance spectroscopy [1H-MRS]) with clinical outcomes after treatment. Thirty consecutive patients with mild or moderate AD were enrolled and randomly divided into one of the two intervention groups: (1) real rTMS with CT (i.e., real group) and (2) sham rTMS with CT (i.e., sham group). 10 Hz rTMS was used to stimulate the left dorsolateral prefrontal cortex (DLPFC) and then to stimulate the left lateral temporal lobe (LTL) for 20 min each day for 4 weeks. Each patient underwent neuropsychological assessment at baseline (T0), immediately after treatment (T1), and 4 weeks after treatment (T2). The ratios of N-acetylaspartate/creatine (NAA/Cr), myoinositol/creatine (mI/Cr), and choline/creatine (Cho/Cr) in the stimulated cortex were measured using 1H-MRS at T0 and T1. Twenty-eight patients were treated with rTMS-CT for 4 weeks. Two patients in the sham group withdrew after being treated several times. Compared with the sham group, the cognitive function and behavior in the real rTMS group improved significantly at T1 and T2. In the real group, compared with the sham group, the NAA/Cr ratio in the left DLPFC was significantly elevated (p = 0.045); however, in the left LTL, it only showed a tendency toward increase (p = 0.162). The change in the NAA/Cr ratio in the left DLPFC was negatively correlated with the change in the cognitive scales of the Alzheimer’s Disease Assessment Scale (ADAS-cog). This study indicated a possible modest effect of rTMS-CT on preventing clinical and neuronal functional deterioration in the left DLPFC of patients with AD. The left DLPFC is a better candidate area than the left LTL.

Introduction: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is an important disease of hospitalized elderly patients, who often have electrolyte imbalances. This study was performed to analyze total serum calcium levels in elderly patients with AECOPD and identify the correlation between hypocalcemia and AECOPD. Methods: 153 elderly patients with AECOPD served as the observation group, and 115 healthy elderly people undergoing physical examinations served as the control group. Differences in the corrected serum calcium, albumin (ALB), and neutrophil/lymphocyte ratio (NLR) were analyzed between the observation and control groups before and after treatment. The incidence of hypocalcemia was compared among patients at different ages and with different pulmonary function classifications before treatment. The relationship between hypocalcemia and respiratory infection was analyzed. Differences in the pretreatment NLR, ALB, logarithm of the serum C-reactive protein level (LogCRP), and hospital stay were compared between patients with and without hypocalcemia. Results: The corrected serum calcium level (P < 0.001), NLR (P = 0.001) and albumin level (P < 0.001) were significantly different among the pretreatment group, post-treatment group, and control group. The serum calcium level, LogCRP, and NLR were significantly lower after than before treatment (P < 0.05). Significant differences in the incidence of hypocalcemia were found among patients of different ages (P = 0.002). The respiratory infection rate (P < 0.001), hospital stay (P < 0.001), NLR (P = 0.007), and LogCRP (P < 0.001) was higher in patients with than without hypocalcemia. However, the albumin level was lower in patients with than without hypocalcemia (P < 0.001). Conclusions: In elderly patients with AECOPD, hypocalcemia may be related to the disease progression, respiratory infection rate, and hospital stay of patients with AECOPD.

BACKGROUND Inflammation plays an important role in the occurrence and development of cancer. Numerous studies have used the derived neutrophil-to-lymphocyte ratio (dNLR) to evaluate prognosis in many types of cancer. However, the relationship between dNLR and ovarian cancer and its value in the differential diagnosis of benign and malignant ovarian tumors remain unknown. METHODS A total of 262 patients with ovarian cancer, 258 with benign ovarian disease, and 232 healthy controls were included in this study. dNLR was calculated using whole blood cell parameters. Receiver operating characteristic curves were generated to obtain sensitivity, specificity, and area under the ROC curve (AUC) to evaluate the diagnostic values of dNLR. RESULTS dNLR was significantly different among the ovarian cancer, benign ovarian disease, and healthy control groups (all P

Chemotherapy resistance of breast cancer poses a great challenge to the survival of patients. During breast cancer treatment, the development of intrinsic and acquired drug resistance tends to further induce adverse prognosis, such as metastasis. In recent years, the progress of research on cytokine-modulated tumor microenvironment and breast cancer stem cells (BCSCs) has shed light on defining the mechanisms of drug resistance gradually. In this review, we have discussed cytokine regulation on breast cancer chemoresistance. Cytokines can affect tumor cell behavior or reprogram tumor niche through specific signaling pathways, thereby regulating the progress of drug resistance. In addition, we summarized the mutually regulatory networks between cytokines and BCSCs in mediating chemoresistance. Cytokines in the tumor microenvironment can regulate the self-renewal and survival of BCSCs in a variety of ways, sequentially promoting chemotherapeutic resistance. Therefore, the combinational treatment of BCSC targeting and cytokine blockade may have a positive effect on the clinical treatment of breast cancer.

Computer-aided diagnosis (CAD) is an attractive topic in Alzheimer's disease (AD) research. Many algorithms are based on a relatively large training dataset. However, small hospitals are usually unable to collect sufficient training samples for robust classification. Although data sharing is expanding in scientific research, it is unclear whether a model based on one dataset is well suited for other data sources. Using a small dataset from a local hospital and a large shared dataset from the AD neuroimaging initiative, we conducted a heterogeneity analysis and found that different functional magnetic resonance imaging data sources show different sample distributions in feature space. In addition, we proposed an effective knowledge transfer method to diminish the disparity among different datasets and improve the classification accuracy on datasets with insufficient training samples. The accuracy increased by approximately 20% compared with that of a model based only on the original small dataset. The results demonstrated that the proposed approach is a novel and effective method for CAD in hospitals with only small training datasets. It solved the challenge of limited sample size in detection of AD, which is a common issue but lack of adequate attention. Furthermore, this paper sheds new light on effective use of multi-source data for neurological disease diagnosis.

Objectives To demonstrate the feasibility of the neurite orientation dispersion and density imaging (NODDI) technique in characterizing the microstructural changes in brain tissues during ischemic stroke and to compare its sensitivity with diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI). Methods Seventy-one patients with hyperacute/acute/subacute ischemic stroke were enrolled in the study. A multishell diffusion magnetic resonance imaging (dMRI) protocol was performed for each subject. Diffusion data were analyzed using the NODDI and diffusional kurtosis estimator toolboxes. Then, NODDI metrics between the lesions and the contralateral tissues were compared to evaluate their values in ischemic stroke. NODDI metrics among different stroke periods and the correlations between NODDI and the duration since stroke onset were analyzed as well. To compare the NODDI's sensitivity with established diffusion techniques, paired t-tests were performed to determine the absolute percentage changes of diffusion metrics between NODDI and DTI/DKI. Results Compared with the contralateral tissues, lesions showed significantly increased values of intracellular volume fraction (Vic) and orientation dispersion index (ODI) and decreased values of isotropic volume fraction (Viso). ODI value was significantly different among three periods and showed fair to good positive correlation with the duration since stroke onset (R = 0.450). NODDI metrics showed significantly larger absolute percentage changes than that of DTI and DKI (P Conclusion NODDI allowed efficient evaluation of microstructural changes in brain tissues during ischemic stroke and showed increased sensitivity compared with DTI and DKI. The possible biophysical mechanisms underlying ischemia could be further elucidated using this advanced diffusion technique.

Using MRSI as comparison, we aimed to explore the difference between amide proton transfer (APT) MRI and conventional semi-solid magnetization transfer ratio (MTR) MRI, and to investigate if molecular APT and structural MTR can provide complimentary information in assessing brain tumors. Seventeen brain tumor patients and 17 age- and gender-matched volunteers were included and scanned with anatomical MRI, APT and MT-weighted MRI, and MRSI. Multi-voxel choline (Cho) and N-acetylaspartic acid (NAA) signals were quantified from MRSI and compared with MTR and MTRasym(3.5ppm) contrasts averaged from corresponding voxels. Correlations between contrasts were explored voxel-by-voxel by pooling values from all voxels into Pearson’s correlation analysis. Differences in correlation coefficients were tested with the Z-test (set at p

Background: Previous studies have indicated that the cognitive deficits in patients with Alzheimer's disease (AD) may be due to topological deteriorations of the brain network. However, whether the selection of a specific frequency band could impact the topological properties is still not clear. Our hypothesis is that the topological properties of AD patients are also frequency-specific. Methods: Resting state functional magnetic resonance imaging data from 10 right-handed moderate AD patients (mean age: 64.3 years; mean mini mental state examination [MMSE]: 18.0) and 10 age and gender-matched healthy controls (mean age: 63.6 years; mean MMSE: 28.2) were enrolled in this study. The global efficiency, the clustering coefficient (CC), the characteristic path length (CpL), and small-world property were calculated in a wide range of thresholds and averaged within each group, at three different frequency bands (0.01-0.06 Hz, 0.06-0.11 Hz, and 0.11-0.25 Hz). Results: At lower-frequency bands (0.01-0.06 Hz, 0.06-0.11 Hz), the global efficiency, the CC and the small-world properties of AD patients decreased compared to controls. While at higher-frequency bands (0.11-0.25 Hz), the CpL was much longer, and the small-world property was disrupted in AD, particularly at a higher threshold. The topological properties changed with different frequency bands, suggesting the existence of disrupted global and local functional organization associated with AD. Conclusions: This study demonstrates that the topological alterations of large-scale functional brain networks in AD patients are frequency dependent, thus providing fundamental support for optimal frequency selection in future related research.

Myeloid-derived suppressor cells (MDSCs) serve an immunosuppressive role in human tumors. Human Lin-/low human leukocyte antigen-antigen D related (HLA-DR-) cluster of differentiation (CD)-11b+CD33+ MDSCs are closely linked with tumor staging, progression, clinical therapeutic efficacy and prognosis for various types of tumors. The present study employed multiparametric flow cytometry to measure the proportion of Lin-/lowHLA-DR-CD11b+CD33+ MDSCs in the peripheral blood of 105 cervical cancer patients and 50 healthy subjects. The level of MDSC was higher in tumor patients than in the normal control group and this was closely associated with clinical staging. Further analysis of tumor-infiltrating MDSCs was performed in 22 patients. The MDSC proportions in tumor tissue were significantly higher than those in the corresponding adjacent tissue. The phenotypic characteristics of Lin-/lowHLA-DR-CD11b+CD33+ MDSCs were then evaluated and the results revealed that they express high CD13 and CD39, and low CD115, CD117, CD124 and programmed cell death ligand 1; they were also devoid of CD14, CD15 and CD66b. MDSCs and T-cells from peripheral blood were sorted by flow cytometry for co-culture experiments. Lin-/lowHLA-DR-CD11b+CD33+ MDSCs from patients significantly inhibited the proliferation of CD4 and CD8 T-cells. Furthermore, functional analysis verified that MDSCs from cervical cancer patients could inhibit interleukin-2 and interferon-γ production from T-cells. In addition, the associations between peripheral circulating MDSCs and tumor infiltrating MDSCs, and tumor relapse and metastasis were analyzed. The number of peripheral MDSCs and MDSCs in tumor tissue were observed to be associated with relapse-free survival. Thus, MDSCs in the peripheral blood and tumors of cervical cancer patients have a significant immunosuppressive effect, and are associated with cervical cancer staging and metastasis. These results suggest that targeting MDSCs may increase antitumor immunity and increase the efficacy of cervical cancer therapies.

Background Perimenopausal insomnia is one of the core symptoms of the menopausal transition. Acupuncture is considered to exert a positive effect on restoring the normal sleep–wake cycle. However, there is little intuitive evidence besides evaluation using clinical effectiveness scales. We therefore designed this study, aiming to use more intuitive and reliable detection techniques such as functional magnetic resonance imaging before and after applying acupuncture to provide neuroimaging evidence, as well as to verify the effectiveness with other curative effect indicators. Methods/Design This study is a randomized, assessor–statistician-blinded, positive medicine controlled trial involving 40 participants. A total of 40 eligible patients with perimenopausal insomnia will be randomly assigned to two groups in a 1:1 ratio as an intervention group using acupuncture and a control group taking estazolam. Participants in the intervention group will receive six acupuncture treatment sessions per week for 4 consecutive weeks, for a total of 24 sessions during the study. Meanwhile, the medicine control group will be prescribed estazolam 1–2 mg/day to be taken 30 minutes before sleep for 4 weeks. The primary outcome is the Pittsburgh Sleep Quality Index. Secondary outcomes are the micro-movement sensitive mattress-type sleep monitoring system, the Hamilton Depression Scale, and the Hamilton Anxiety Scale. All outcomes will be evaluated before and after treatment. The safety of interventions will be assessed at every visit. Discussion The results of this trial, which will be available in 2018, will investigate the impact of acupuncture treating perimenopausal insomnia from assessment of the sleep architecture, hormone level, and emotional-circuit neurological function, and will uncover the effective mechanism of acupuncture regulating the emotional center integrated effect. Trial registration Chinese Clinical Trials Register, ChCTR-IPC-16007832. Registered on 26 January 2016. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2072-7) contains supplementary material, which is available to authorized users.

Background: The red cell distribution width (RDW) has attracted attention in the diagnosis of malignant tumors. In this study, we analyzed the correlation between the RDW and ovarian cancer by observing changes in the RDW in patients with ovarian cancer. Methods: Patients diagnosed with ovarian cancer at the First Affiliated Hospital of Guangxi Medical University, China, from 2012 to 2016, were retrospectively analyzed. Patients diagnosed with ovarian benign tumors in our hospital during the same period comprised the control group. Differences in relevant indicators were compared between the ovarian cancer and control groups using the Mann–Whitney U test. Differences in the RDW at different stages of ovarian cancer were compared using one-way analysis of variance. Correlations between the RDW and experimental parameters in patients with ovarian cancer were analyzed by Spearman correlation. Results: The RDW, absolute neutrophil count (N), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and cancer antigen 125 (CA-125) concentration were significantly higher in the ovarian cancer than control group. The hemoglobin concentration (Hb) and absolute lymphocyte count (L) were significantly lower in the ovarian cancer than control group. The RDW was significantly different among 4 different stages of ovarian cancer. Correlation analysis demonstrated that the RDW was negatively correlated with the hemoglobin concentration (Hb). The RDW was positively correlated with the cancer stage, NLR, PLR, and CA-125 concentration. The area under the receiver-operating characteristic curve of the RDW was 0.876 (95% confidence interval 0.829–0.923). Conclusion: The RDW is associated with ovarian cancer and is a potential marker of its progression.

Imaging markers derived from magnetic resonance images, together with machine learning techniques allow for the recognition of unique anatomical patterns and further differentiating Alzheimer's disease (AD) from normal states. T1-based imaging markers, especially volumetric patterns have demonstrated their discriminative potential, however, rely on the tissue abnormalities of gray matter alone. White matter abnormalities and their contribution to AD discrimination have been studied by measuring voxel-based intensities in diffusion tensor images (DTI); however, no systematic study has been done on the discriminative power of either region-of-interest (ROI)-based features from DTI or the combined features extracted from both T1 images and DTI. ROI-based analysis could potentially reduce the feature dimensionality of DTI indices, usually from more than 10e + 5, to 10–150 which is almost equal to the order of magnitude with respect to volumetric features from T1. Therefore it allows for straight forward combination of intensity based landmarks of DTI indices and volumetric features of T1. In the present study, the feasibility of tract-based features related to Alzheimer's disease was first evaluated by measuring its discriminative capability using support vector machine on fractional anisotropy (FA) maps collected from 21 subjects with Alzheimer's disease and 15 normal controls. Then the performance of the tract-based FA + gray matter volumes-combined feature was evaluated by cross-validation. The combined feature yielded good classification result with 94.3% accuracy, 95.0% sensitivity, 93.3% specificity, and 0.96 area under the receiver operating characteristic curve. The tract-based FA and the tract-based FA + gray matter volumes-combined features are certified their feasibilities for the recognition of anatomical features and may serve to complement classification methods based on other imaging markers.

To investigate the functional connectome alterations in cerebral small-vessel disease (CSVD) patients with thalamus lacunes and its relation to cognitive impairment. This case-control study was approved by the local research ethics committee, and all participants provided informed consent. There were 14 CSVD patients with thalamus lacunes (CSVDw.), 27 without (CSVDwo.), and 34 healthy controls (HC) recruited matched for age, sex, and education to undergo a 3T resting-state functional MR examination. The whole-brain functional connectome was constructed by thresholding the Pearson correlation matrices of 90 brain regions, and the topologic properties were analyzed by using graph theory approaches. Networks were compared between CSVD patients and HC, and associations between network measures and cognitive function were tested. Compared with HC, the functional connectome in CSVDw. patients showed abnormalities at the global level and at the nodal level (P .05). The configurations of brain functional connectome in CSVDw. patients were perturbed but not obvious for those without, and correlated with the mild cognitive impairment, especially for EM and PS. This study suggested that lacunes on thalamus played a vital role in mediating the neural functional changes of CSVD patients.

Accurate landslide inventory mapping is essential for quantitative hazard and risk assessment. Although multi-temporal change detection techniques have contributed greatly to landslide inventory preparation, it is still challenging to generate quality change detection images (CDIs) for accurate landslide mapping. The recently proposed change detection-based Markov random field (CDMRF) provides an effective approach for rapid mapping of landslides with minimum user interventions. However, when CDI is generated by change vector analysis (CVA) alone, the CDMRF method may suffer from noise especially when the pre- and post-event remote sensing images are acquired under different atmospheric, illumination, and phenological conditions. This paper improved such CDMRF approach by integrating normalized difference vegetation index (NDVI), principal component analysis (PCA), and independent component analysis (ICA) generated CDIs with MRF for landslide inventory mapping from multi-sensor data. To justify the effectiveness and applicability, the improved methods were applied to map rainfall-, typhoon-, and earthquake-triggered landslides from the pre- and post-event satellite images acquired by very high resolution QuickBird, high resolution FORMOSAT-2, and moderate resolution Sentinel-2. Moreover, they were tested on pre-event Landsat-8 and post-event Sentinel-2 datasets, indicating that they are operational for landslide inventory mapping from combined multi-temporal and multi-sensor data. The results demonstrate that the improved δNDVI-, PCA-, and ICA-based approaches perform much better than CVA-based CDMRF in terms of completeness, correctness, Kappa coefficient, and F-measures. To the best of our knowledge, it is the first time that NDVI, PCA, and ICA are integrated with MRF for landslide inventory mapping from multi-sensor data. It is anticipated that this research can be a starting point for developing new change detection techniques that can readily generate quality CDI and for applying advanced machine learning algorithms (e.g., deep learning) to automatic detection of natural hazards from multi-sensor time series data.

Increasing evidence has demonstrated that white matter (WM) disruptions, due to the injury of the axon and myelin, play an important role in the pathogenesis of Alzheimer's disease (AD). Diffusion tensor imaging (DTI) is a sensitive modality to evaluate the WM integrity in both AD patients and animal models. In this study, an advanced DTI modality, employing a 7.0-T magnetic resonance imaging system, was used to analyze WM changes across the whole brain of an amyloid precursor protein/presenilin 1 (APP/PS1) mouse model. A voxel-based analysis was used to compare the quantitative DTI parameters automatically in both APP/PS1 mice (n = 9) and wild-type (WT) controls (n = 9). After DTI examination, the ultrastructure analysis was compared with DTI findings. Compared with WT controls, gray matter (GM) areas in APP/PS1 mice such as the cingulate cortex and the striatum showed significant fractional anisotropy (FA) and axial diffusivity (DA) increase, while the thalamus only showed a significant FA increase (p < 0.01). Similarly, a significant mean diffusivity, DA, and radial diffusivity increase was observed in the bilateral neocortex (p < 0.01). The left hippocampus only showed significant FA increase in APP/PS1 mice (p < 0.01). The changes in WM regions were detected in the forceps minor of the corpus callosum, the anterior part of the anterior commissure, and the internal capsule, with a significant FA or DA increase (p < 0.01). Abnormalities derived from diffusion measurements were in-line with the ultrastructure findings, including extensive pathological damage of the neurons, neutrophils, and vessels. In conclusion, voxel-based diffusion tensor imaging can detect diffusion alterations not only in GM but also in WM areas in AD models, reflecting the extensive pathological changes of AD.

Peripheral nerve damage does not fully explain the pathogenesis of trigeminal neuralgia (TN). Central nervous system changes can follow trigeminal nerve dysfunction. We hypothesized that brain white matter and functional connectivity changes in TN patients were involved in pain perception, modulation, the cognitive-affective system, and motor function; moreover, changes in functional reorganization were correlated with white matter alterations. Twenty left TN patients and twenty-two healthy controls were studied. Diffusion kurtosis imaging was analyzed to extract diffusion and kurtosis parameters, and functional connectivity density (FCD) mapping was used to explore the functional reorganization in the brain. In the patient group, we found lower axial kurtosis and higher axial diffusivity in tracts participated in sensory, cognitive-affective, and modulatory aspects of pain, such as the corticospinal tract, superior longitudinal fasciculus, anterior thalamic radiation, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, cingulated gyrus, forceps major and uncinate fasciculus. Patients exhibited complex FCD reorganization of hippocampus, striatum, thalamus, precentral gyrus, precuneus, prefrontal cortex and inferior parietal lobule in multiple modulatory networks that played crucial roles in pain perception, modulation, cognitive-affective system, and motor function. Further, the correlated structural-functional changes may be responsible for the persistence of long-term recurrent pain and sensory-related dysfunction in TN.

It's very common to see many regions of the blur in the pictures because of the relative movement of the subject and the shooting equipment, which causes much difficulty for the subsequent processing such as information extraction. This paper proposes a new method to solve the problem by using the continuous motion kernel. We first get multi-frame images from the CCD system and thus estimate the velocitydisplacement curve, then we will get the initial velocity and the acceleration of the object by the curve. After that, we will take the initial velocity and the acceleration into the continuous blur kernel equation, thus we can get the blur kernel of the each point of the image. Finally we will adopt the Richardson-Lucy iterative deconvolution by point operations to recover the image. The experimental result demonstrated that our method can eliminate the blur of the image more accurately compared to some state-of-the-art methods using the single blur kernel.