IodoTMT-labeled redox proteomics reveals the involvement of oxidative post-translational modification in response to para-hydroxybenzoic acid and hydrogen peroxide stresses in poplar.

Poplar is widely planted as an economic and ecological tree species. However, accumulation of the phenolic acid allelochemical para-hydroxybenzoic acid (pHBA) in soil is a severe threat to the growth and productivity of poplar. pHBA stress leads to excessive production of reactive oxygen species (ROS). However, it is unclear which redox-sensitive proteins are involved in the pHBA-induced cellular homeostasis regulatory mechanism. We here identified reversible redox-modified proteins and modified cysteine (Cys) sites in exogenous pHBA- and hydrogen peroxide (H2O2)-treated poplar seedling leaves by using the iodoacetyl tandem mass tag-labeled redox proteomics method. In total, 4786 redox modification sites were identified in 3176 proteins, with 104 and 91 proteins being differentially modified at 118 and 101 Cys sites in response to pHBA and H2O2 stresses, respectively. The differentially modified proteins (DMPs) were predicted to be mainly localized in the chloroplast and cytoplasm, with most proteins being enzymes with catalytic activities. The KEGG enrichment analysis of these DMPs revealed that proteins related to the MAPK signaling pathway, soluble sugar metabolism, amino acid metabolism, photosynthesis, and phagosome pathways were extensively regulated by redox modifications. Moreover, combined with our previous quantitative proteomics data, 8 proteins were upregulated and oxidized under both pHBA and H2O2 stresses. Reversible oxidation of Cys sites in these proteins might be actively responsible for the regulation of tolerance to pHBA-induced oxidative stress. Based on the aforementioned results, a redox regulatory model activated by pHBA- and H2O2-induced oxidative stress was proposed. This study conducts the first redox proteomics analysis of poplar in response to pHBA stress and provides a new insight into the mechanistic framework of reversible oxidative post-translational modifications to gain a better understanding of pHBA-induced chemosensory effects on poplar.

Underwater image enhancement based on color correction and complementary dual image multi-scale fusion.

Underwater images often suffer from color cast, poor contrast, and detail loss owing to the scattering and absorption of light in water. To solve these problems, we propose what we believe to be a novel underwater image enhancement method based on color correction and dual image multi-scale fusion. We first use the color correction method to solve the problem of color cast, and we compensate the other two-color channels with the highest mean value color channel; further, all the color channels are dynamically stretched. Next, a complementary dual image multi-scale fusion method is used to improve the contrast, pairs of complementary adaptive gamma correction with weighted distribution enhanced images are used as the two inputs of multi-scale fusion, and appropriate weight maps are selected. Then, a multi-scale detail-sharpening method is used to enhance the image details. Qualitative and quantitative evaluations prove that the proposed method can produce high-quality underwater images. Moreover, the proposed method has relatively high evaluator values compared to the state-of-the-art methods.

Evaluating intracranial artery dissection by using three-dimensional simultaneous non-contrast angiography and intra-plaque hemorrhage high-resolution magnetic resonance imaging: a retrospective study.

BACKGROUND: There was no previous report on the three-dimensional simultaneous non-contrast angiography and intra-plaque hemorrhage (3D-SNAP) magnetic resonance imaging (MRI) sequence to diagnose intracranial artery dissection (IAD). PURPOSE: To improve the diagnostic accuracy and guide the clinical treatment for IAD by elucidating its pathological features using 3D-SNAP MRI. MATERIAL AND METHODS: From January 2015 to September 2018, 113 patients with suspected IAD were analyzed. They were divided into IAD and non-IAD groups according to the spontaneous coronary artery dissection (SCAD) criteria. All patients underwent 3D-SNAP, 3D-TOF, T2W imaging, 3D-PD, 3D-T1W-VISTA, and 3D-T1WCE) using 3.0-T MRI; clinical data were collected. The IAD imaging findings (intramural hematoma, double lumen, intimal flap, aneurysmal dilatation, stenosis, or occlusion) in every sequence were analyzed. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic efficiency of each sequence. RESULTS: There was a significant difference in the probability of intramural hematoma, relative signal intensity of intramural hematoma, double lumen, stenosis, or occlusion signs on 3D-TOF, T2W, 3D-PD, 3D-T1W-VISTA, 3D-SNAP, and 3D-T1WCE sequences (P<0.05). The 3D-SNAP and 3D-T1WCE sequences were most sensitive for diagnosing intramural hematoma and displaying double-lumen signs, respectively. The diagnostic efficiency of the 3D-SNAP sequence combined with 3D-T1WCE was the highest (area under the curve [AUC] 0.966). The AUC value of the 3D-SNAP sequence (AUC 0.897) was slightly inferior to that of 3D-T1W enhancement (AUC 0.903). CONCLUSION: 3D-SNAP MRI is a non-invasive and effective method and had the greatest potential among those methods tested for improving the diagnostic accuracy for IAD.

Combined Assessment of Elevated Plasma Lipoprotein-Associated Phospholipase A2 and Plaque Enhancement Improved Accuracy in the Risk of Acute Ischemic Stroke in Patients with Intracranial Artery Stenosis.

PURPOSE: We evaluated the relationship between plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) concentration and plaque characteristics in patients with intracranial artery stenosis and their clinical relevance in acute ischemic stroke. METHODS: Eighty-seven patients with intracranial atherosclerotic stenosis (66 males, 21 females) were retrospectively enrolled. Plasma Lp-PLA2 concentration was measured, and vessel wall magnetic resonance imaging (VW-MRI) was used to determine intracranial vascular stenosis and plaque characteristics, including plaque enhancement, surface morphology, and T1 hyperintensity. Binary logistic regression was used to evaluate the relationship between Lp-PLA2 concentration and plaque characteristics of intracranial artery after adjusting for demographic and confounding factors and to assess their diagnostic efficacy for the risk of acute ischemic stroke. RESULTS: After adjustment for demographic, medication and related lipid factors, Lp-PLA2 elevation was associated with plaque enhancement (odds ratio [OR]=12.7, 95% confidence interval [CI] 2.51-64.82, P=0.002) and surface irregularity (OR=2.9, 95% CI 1.06-7.98, P=0.038). Both Lp-PLA2 elevation (OR=8.8, 95% CI 1.64-47.72, P=0.011) and plaque enhancement (OR=34.3, 95% CI 5.88-200.4, P=0.001) were associated with acute ischemic stroke. Receiver operating characteristic curve analysis showed that the area under the curve for Lp-PLA2 concentration and plaque enhancement combined in the diagnosis of acute ischemic stroke was 0.884, significantly higher than that for Lp-PLA2 concentration (0.724) and plaque enhancement (0.794) alone. CONCLUSION: Elevated Lp-PLA2 is associated with plaque enhancement and plaque surface irregularity. Combined assessment of Lp-PLA2 concentration and plaque enhancement is of greater diagnostic value for the risk of acute ischemic stroke in patients with intracranial artery stenosis.

[Dexamethasone Blocks Adriamycin-induced Podocytes'Mobility via Impacting Nephrin Expression].

OBJECTIVE: To explore how dexamethasone (Dex) directly restores kidney podocyte function in adriamycin (ADR)-induced nephrotic model and the effects of Dex on the motility of podocytes, to analyze whether nephrin is a key signal molecule in the process. METHODS: The cultured podocytes were divided into three growps: ADR treated group, ADR+Dex group, blank control group. The analyses of podocytes function were performed using scrape-wound, Transwell migration assays and FITC-BSA. Quantitative real-time PCR and Western blot were used to test the expression of nephrin. Male SD rats were used to generate ADR-induced nephrology model, and randomly divided into three groups: ADR group, ADR+Dex group and normal group. At 7 d, 14 d, 21 d and 28 d after ADR injection, 24 h urine protein was measured as well. Podocyte foot process effacement was observed under transmission electron microscopy. RESULTS: Podocytes' motility, permeability of a monolayer of podocytes incubated with FITC-BSA, the expression of nephrin were higher in ADR group than those in blank control group (P<0.05); on the contrary, the indexes above in Dex+ADR group were decreased when compared with ADR group (P<0.05). 24 h urine protein increased significantly at day 14 (vs. normal group P<0.001) and peaked at day 28 in ADR rats (vs. normal group P<0.001), whereas decreased at day 14, 21 and 28 in Dex+ADR group (vs. ADR group, P<0.001). The FWP of ADR-treated rats was greater than normal group and Dex+ADR group (P<0.01). CONCLUSION: Dex impacts the expression of nephrin, relieves the enhanced motility induced by ADR and decreases urine protein level.

[Effect and molecular mechanism of interferon-α on podocyte apoptosis induced by hepatitis B virus X protein].

OBJECTIVE: To investigate the effect and molecular mechanism of interferon-α (INF-α) on the apoptosis of the mouse podocyte cell line MPC5 induced by hepatitis B virus X (HBx) protein. METHODS: MPC5 cells were transfected with the pEX plasmid carrying the HBx gene. RT-PCR was used to measure the mRNA expression of HBx at different time points. MPC5 cells were divided into 4 groups: control group (MPC5 cells cultured under normal conditions), INF-α group (MPC5 cells cultured with INF-α), HBx group (MPC5 cells induced by HBx), and HBx+INF-α group (MPC5 cells induced by HBx and cultured with INF-α). After 48 hours of intervention under different experimental conditions, flow cytometry was used to measure the apoptosis of MPC5 cells, and quantitative real-time PCR and Western blot were used to measure the mRNA and protein expression of slit diaphragm-related proteins (nephrin, CD2AP, and synaptopodin) and the cytoskeleton-related protein transient receptor potential cation channel 6 (TRPC6). RESULTS: MPC5 cells transfected by pEX-HBx had the highest expression of HBx mRNA at 48 hours after transfection (P<0.05). Compared with the control, INF-α and HBx+INF-α groups, the HBx group had a significant increase in the apoptosis rate of MPC5 cells (P<0.05). Compared with the control and INF-α groups, the HBx group had significant reductions in the mRNA and protein expression of nephrin, synaptopodin, and CD2AP and significant increases in the mRNA and protein expression of TRPC6 (P<0.05). Compared with the HBx group, the HBx+INF-α group had significant increases in the mRNA and protein expression of nephrin, synaptopodin, and CD2AP and significant reductions in the mRNA and protein expression of TRPC6 (P<0.05). CONCLUSIONS: INF-α can inhibit the apoptosis of podocytes induced by HBx, possibly through improving the abnormal expression of slit diaphragm-related proteins (CD2AP, nephrin, and synaptopodin) and cytoskeleton-related protein (TRPC6) induced by HBx.

A meta-analysis of use of Prostate Imaging Reporting and Data System Version 2 (PI-RADS V2) with multiparametric MR imaging for the detection of prostate cancer.

OBJECTIVES: This meta-analysis was undertaken to review the diagnostic accuracy of PI-RADS V2 for prostate cancer (PCa) detection with multiparametric MR (mp-MR). METHODS: A comprehensive literature search of electronic databases was performed by two observers independently. Inclusion criteria were original research using the PI-RADS V2 system in reporting prostate MRI. The methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Data necessary to complete 2 × 2 contingency tables were obtained from the included studies. RESULTS: Thirteen studies (2,049 patients) were analysed. This is an initial meta-analysis of PI-RADs V2 and the overall diagnostic accuracy in diagnosing PCa was as follows: pooled sensitivity, 0.85 (0.78-0.91); pooled specificity, 0.71 (0.60-0.80); pooled positive likelihood ratio (LR+), 2.92 (2.09-4.09); pooled negative likelihood ratio (LR-), 0.21 (0.14-0.31); pooled diagnostic odds ratio (DOR), 14.08 (7.93-25.01), respectively. Positive predictive values ranged from 0.54 to 0.97 and negative predictive values ranged from 0.26 to 0.92. CONCLUSION: Currently available evidence indicates that PI-RADS V2 appears to have good diagnostic accuracy in patients with PCa lesions with high sensitivity and moderate specificity. However, no recommendation regarding the best threshold can be provided because of heterogeneity. KEY POINTS: • PI-RADS V2 shows good diagnostic accuracy for PCa detection. • Initially pooled specificity of PI-RADS v2 remains moderate. • PCa detection is increased by experienced radiologists. • There is currently a high heterogeneity in prostate diagnostics with MRI.

Health Insurance and Health Care among the Mid-Aged and Older Chinese: Evidence from the National Baseline Survey of CHARLS.

We document the recent profile of health insurance and health care among mid-aged and older Chinese using data from the China Health and Retirement Longitudinal Study conducted in 2011. Overall health insurance coverage is about 93%. Multivariate regressions show that respondents with lower income as measured by per capita expenditure have a lower chance of being insured, as do the less-educated, older, and divorced/widowed women and rural-registered people. Premiums and reimbursement rates of health insurance vary significantly by schemes. Inpatient reimbursement rates for urban people increase with total cost to a plateau of 60%; rural people receive much less. Demographic characteristics such as age, education, marriage status, per capita expenditure, and self-reported health status are not significantly associated with share of out-of-pocket cost after controlling community effects. For health service use, we find large gaps that vary across health insurance plans, especially for inpatient service. People with access to urban health insurance plans are more likely to use health services. In general, Chinese people have easy access to median low-level medical facilities. It is also not difficult to access general hospitals or specialized hospitals, but there exists better access to healthcare facilities in urban areas. Copyright © 2016 John Wiley & Sons, Ltd.

Health Insurance and Health Status: Exploring the Causal Effect from a Policy Intervention.

Whether health insurance matters for health has long been a central issue for debate when assessing the full value of health insurance coverage in both developed and developing countries. In 2007, the government-led Urban Resident Basic Medical Insurance (URBMI) program was piloted in China, followed by a nationwide implementation in 2009. Different premium subsidies by government across cities and groups provide a unique opportunity to employ the instrumental variables estimation approach to identify the causal effects of health insurance on health. Using a national panel survey of the URBMI, we find that URBMI beneficiaries experience statistically better health than the uninsured. Furthermore, the insurance health benefit appears to be stronger for groups with disadvantaged education and income than for their counterparts. In addition, the insured receive more and better inpatient care, without paying more for services. Copyright © 2015 John Wiley & Sons, Ltd.

Accuracy of combined dynamic contrast-enhanced magnetic resonance imaging and diffusion-weighted imaging for breast cancer detection: a meta-analysis.

BACKGROUND: Magnetic resonance imaging (MRI) is increasingly being used to examine patients with suspected breast cancer. PURPOSE: To determine the diagnostic performance of combined dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) for breast cancer detection. MATERIAL AND METHODS: A comprehensive search of the PUBMED, EMBASE, Web of Science, and Cochrane Library databases was performed up to September 2014. Statistical analysis included pooling of sensitivity and specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and diagnostic accuracy using the summary receiver operating characteristic (SROC). All analyses were conducted using STATA (version 12.0), RevMan (version 5.2), and Meta-Disc 1.4 software programs. RESULTS: Fourteen studies were analyzed, which included a total of 1140 patients with 1276 breast lesions. The pooled sensitivity and specificity of combined DCE-MRI and DWI were 91.6% and 85.5%, respectively. The pooled sensitivity and specificity of DWI-MRI were 86.0% and 75.6%, respectively. The pooled sensitivity and specificity of DCE-MRI were 93.2% and 71.1%. The area under the SROC curve (AUC-SROC) of combined DCE-MRI and DWI was 0.94, the DCE-MRI of 0.85. Deeks testing confirmed no significant publication bias in all studies. CONCLUSION: Combined DCE-MRI and DWI had superior diagnostic accuracy than either DCE-MRI or DWI alone for the diagnosis of breast cancer.

[Clinical and pathological differences between children with various genotypes of hepatitis B virus-associated glomerulonephritis].

OBJECTIVE: To compare the clinical and pathological features between children with various genotypes of hepatitis B virus-associated glomerulonephritis (HBV-GN). METHODS: Forty-one children with HBV-GN concurrently undergoing liver and renal biopsy were randomly selected. Serum specimens were collected for genotyping and hepatitis B virus (HBV) cccDNA assay. The clinical, pathological, and HBV cccDNA differences between HBV-GN children of various genotypes were analyzed. RESULTS: Among the 41 HBV-GN children, 29 (71%) were genotype C, 10 (24%) were genotype B, and 2 (5%) were genotype B/C. The incidence rates of hematuria, albuminuria, complement 3 decrease, alanine transaminase increase, and renal insufficiency in the genotype C group were significantly higher than those in the genotype B group (P<0.05). Similarly, the HBV cccDNA positive rate was significantly higher in the genotype C group than that in the genotype B group. No difference was observed in the distribution of pathological types of renal tissues betwee the two geonotype groups. There were no significant differences in the degrees of hepatic inflammation and fibrosis between the two groups. CONCLUSIONS: Mainly genotypes C and B occur in children with HBV-GN and the former genotype is dominant. The clinical symptoms of patients with genotype C are more serious than those with genotype B. However, there is no difference in the pathological features between them.

Comparison of clinical and MRI features of brain metastases between ALK+ and ALK- NSCLC.

BACKGROUND: Non-small-cell lung cancer (NSCLC) is the primary cause of brain metastases (BM). This study aimed to investigate differences in clinical and magnetic resonance imaging (MRI) features of BM between anaplastic lymphoma kinase (ALK) gene fusion (ALK+) and ALK wild-type (ALK-) NSCLC, and to preliminarily assess the efficacy of radiotherapy for treating BM. METHODS: A retrospective analysis included 101 epidermal growth factor receptor (EGFR)- NSCLC patients with BM: 41 with ALK gene fusion and 60 being ALK-. The brain MRI and clinical features were compared between different ALK status using the multivariate analysis, and a nomogram was constructed to predict ALK gene fusion. Fifty-six patients who did not undergo cerebral surgery and had complete pre- and post- treatment data were further divided based on whether they received radiotherapy. Log-rank test was used to compare the short-term effect of treatment between the two groups under different genotypes. RESULTS: ALK+ BM exhibited decreased peritumoral brain edema size, lower peritumoral brain edema index (PBEI), and a more homogeneous contrast enhancement pattern compared to ALK- BM. Age (OR = 1.04; 95%CI: 1.02-1.06), time to BM (OR = 1.50; 95% CI: 1.04-2.14), PBEI (OR = 1.26; 95% CI: 0.97-1.62), smoking status (smoking index >400 vs. non-smoking status: OR = 1.42; 95% CI: 0.99-2.04) and contrast enhancement pattern (OR = 1.89; 95% CI: 1.28-2.78) were associated with ALK gene fusion. A nomogram based on these variables demonstrated acceptable predictive efficiency (AUC = 0.844). In the ALK+ group, patients who received radiotherapy did not show increased disease control rate (DCR) or progression-free survival (PFS). In contrast, in the ALK- group, those who received radiotherapy had improved objective response rate (ORR), DCR, and PFS compared to those who were only treated with systemic therapy. CONCLUSIONS: The clinical and MRI features of BM can indicate the status of ALK in NSCLC. In the ALK- group, patients who received radiotherapy showed higher ORR, DCR, and PFS compared to those who did not.

Meta-analysis of dynamic contrast enhancement and diffusion-weighted MRI for differentiation of benign from malignant non-mass enhancement breast lesions.

Purpose: The objective of this study was to conduct a meta-analysis comparing the diagnostic efficacy of models based on diffusion-weighted imaging (DWI)-MRI, dynamic contrast enhancement (DCE)-MRI, and combination models (DCE and DWI) in distinguishing benign from malignant non-mass enhancement (NME) breast lesions. Materials and methods: PubMed, Embase, and Cochrane Library were searched, from inception to January 30, 2023, for studies that used DCE or DWI-MRI for the prediction of NME breast cancer patients. A bivariate random-effects model was used to calculate the meta-analytic sensitivity, specificity, and area under the curve (AUC) of the DCE, DWI, and combination models. Subgroup analysis and meta-regression analysis were performed to find the source of heterogeneity. Results: Of the 838 articles screened, 18 were eligible for analysis (13 on DCE, five on DWI, and four studies reporting the diagnostic accuracy of both DCE and DWI). The funnel plot showed no publication bias (p > 0.5). The pooled sensitivity and specificity and the AUC of the DCE, DWI, and combination models were 0.58, 0.72, and 0.70, respectively; 0.84, 0.69, and 0.84, respectively; and 0.88, 0.79, 0.90, respectively. The meta-analysis found no evidence of a threshold effect and significant heterogeneity among trials in terms of DCE sensitivity and specificity, as well as DWI specificity alone (I2 > 75%). The meta-regression revealed that different diagnostic criteria contributed to the DCE study's heterogeneity (p < 0.05). Different reference criteria significantly influenced the heterogeneity of the DWI model (p < 0.05). Subgroup analysis revealed that clustered ring enhancement (CRE) had the highest pooled specificity (0.92) among other DCE features. The apparent diffusion coefficient (ADC) with a mean threshold <1.3 × 10-3 mm2/s had a slightly higher sensitivity of 0.86 compared to 0.82 with an ADC of ≥1.3 × 10-3 mm2/s. Conclusion: The combination model (DCE and DWI) outperformed DCE or DWI alone in identifying benign and malignant NME lesions. The DCE-CRE feature was the most specific test for ruling in NME cancers.

Prediction of histopathologic grades of bladder cancer with radiomics based on MRI: Comparison with traditional MRI.

PURPOSE: To compare biparametric magnetic resonance imaging (bp-MRI) radiomics signatures and traditional MRI model for the preoperative prediction of bladder cancer (BCa) grade. MATERIALS AND METHODS: This retrospective study included 255 consecutive patients with pathologically confirmed 113 low-grade and 142 high-grade BCa. The traditional MRI nomogram model was developed using univariate and multivariate logistic regression by the mean apparent diffusion coefficient (ADC), vesical imaging reporting and data system, tumor size, and the number of tumors. Volumes of interest were manually drawn on T2-weighted imaging (T2WI) and ADC maps by 2 radiologists. Using one-way analysis of variance, correlation, and least absolute shrinkage and selection operator methods to select features. Then, a logistic regression classifier was used to develop the radiomics signatures. Receiver operating characteristic (ROC) analysis was used to compare the diagnostic abilities of the radiomics and traditional MRI models by the DeLong test. Finally, decision curve analysis was performed by estimating the clinical usefulness of the 2 models. RESULTS: The area under the ROC curves (AUCs) of the traditional MRI model were 0.841 in the training cohort and 0.806 in the validation cohort. The AUCs of the 3 groups of radiomics model [ADC, T2WI, bp-MRI (ADC and T2WI)] were 0.888, 0.875, and 0.899 in the training cohort and 0.863, 0.805, and 0.867 in the validation cohort, respectively. The combined radiomics model achieved higher AUCs than the traditional MRI model. decision curve analysis indicated that the radiomics model had higher net benefits than the traditional MRI model. CONCLUSION: The bp-MRI radiomics model may help distinguish high-grade and low-grade BCa and outperforming the traditional MRI model. Multicenter validation is needed to acquire high-level evidence for its clinical application.

Altered cortical thickness-based structural covariance networks in type 2 diabetes mellitus.

Cognitive impairment is a common complication of type 2 diabetes mellitus (T2DM), and early cognitive dysfunction may be associated with abnormal changes in the cerebral cortex. This retrospective study aimed to investigate the cortical thickness-based structural topological network changes in T2DM patients without mild cognitive impairment (MCI). Fifty-six T2DM patients and 59 healthy controls underwent neuropsychological assessments and sagittal 3-dimensional T1-weighted structural magnetic resonance imaging. Then, we combined cortical thickness-based assessments with graph theoretical analysis to explore the abnormalities in structural covariance networks in T2DM patients. Correlation analyses were performed to investigate the relationship between the altered topological parameters and cognitive/clinical variables. T2DM patients exhibited significantly lower clustering coefficient (C) and local efficiency (Elocal) values and showed nodal property disorders in the occipital cortical, inferior temporal, and inferior frontal regions, the precuneus, and the precentral and insular gyri. Moreover, the structural topological network changes in multiple nodes were correlated with the findings of neuropsychological tests in T2DM patients. Thus, while T2DM patients without MCI showed a relatively normal global network, the local topological organization of the structural network was disordered. Moreover, the impaired ventral visual pathway may be involved in the neural mechanism of visual cognitive impairment in T2DM patients. This study enriched the characteristics of gray matter structure changes in early cognitive dysfunction in T2DM patients.

Analysis of white matter tract integrity using diffusion kurtosis imaging reveals the correlation of white matter microstructural abnormalities with cognitive impairment in type 2 diabetes mellitus.

Background: This study aimed to identify disruptions in white matter integrity in type 2 diabetes mellitus (T2DM) patients by utilizing the white matter tract integrity (WMTI) model, which describes compartment-specific diffusivities in the intra- and extra-axonal spaces, and to investigate the relationship between WMTI metrics and clinical and cognitive measurements. Methods: A total of 73 patients with T2DM and 57 healthy controls (HCs) matched for age, sex, and education level were enrolled and underwent diffusional kurtosis imaging and cognitive assessments. Tract-based spatial statistics (TBSS) and atlas-based region of interest (ROI) analysis were performed to compare group differences in diffusional metrics, including fractional anisotropy (FA), mean diffusivity (MD), axonal water fraction (AWF), intra-axonal diffusivity (Daxon), axial extra-axonal space diffusivity (De,//), and radial extra-axonal space diffusivity (De,⊥) in multiple white matter (WM) regions. Relationships between diffusional metrics and clinical and cognitive functions were characterized. Results: In the TBSS analysis, the T2DM group exhibited decreased FA and AWF and increased MD, De,∥, and De,⊥ in widespread WM regions in comparison with the HC group, which involved 56.28%, 32.07%, 73.77%, 50.47%, and 75.96% of the mean WM skeleton, respectively (P < 0.05, TFCE-corrected). De,⊥ detected most of the WM changes, which were mainly located in the corpus callosum, internal capsule, external capsule, corona radiata, posterior thalamic radiations, sagittal stratum, cingulum (cingulate gyrus), fornix (stria terminalis), superior longitudinal fasciculus, and uniform fasciculus. Additionally, De,⊥ in the genu of the corpus callosum was significantly correlated with worse performance in TMT-A (ß = 0.433, P < 0.001) and a longer disease duration (ß = 0.438, P < 0.001). Conclusions: WMTI is more sensitive than diffusion tensor imaging in detecting T2DM-related WM microstructure abnormalities and can provide novel insights into the possible pathological changes underlying WM degeneration in T2DM. De,⊥ could be a potential imaging marker in monitoring disease progression in the brain and early intervention treatment for the cognitive impairment in T2DM.

Genetic associations with longevity are on average stronger in females than in males.

It is long observed that females tend to live longer than males in nearly every country. However, the underlying mechanism remains elusive. In this study, we discovered that genetic associations with longevity are on average stronger in females than in males through bio-demographic analyses of genome-wide association studies (GWAS) dataset of 2178 centenarians and 2299 middle-age controls of Chinese Longitudinal Healthy Longevity Study (CLHLS). This discovery is replicated across North and South regions of China, and is further confirmed by North-South discovery/replication analyses of different and independent datasets of Chinese healthy aging candidate genes with CLHLS participants who are not in CLHLS GWAS, including 2972 centenarians and 1992 middle-age controls. Our polygenic risk score analyses of eight exclusive groups of sex-specific genes, analyses of sex-specific and not-sex-specific individual genes, and Genome-wide Complex Trait Analysis using all SNPs all reconfirm that genetic associations with longevity are on average stronger in females than in males. Our discovery/replication analyses are based on genetic datasets of in total 5150 centenarians and compatible middle-age controls, which comprises the worldwide largest sample of centenarians. The present study's findings may partially explain the well-known male-female health-survival paradox and suggest that genetic variants may be associated with different reactions between males and females to the same vaccine, drug treatment and/or nutritional intervention. Thus, our findings provide evidence to steer away from traditional view that "one-size-fits-all" for clinical interventions, and to consider sex differences for improving healthcare efficiency. We suggest future investigations focusing on effects of interactions between sex-specific genetic variants and environment on longevity as well as biological function.

Decreased ALFF and Functional Connectivity of the Thalamus in Vestibular Migraine Patients.

BACKGROUND: The thalamus has been reported to be associated with pain modulation and processing. However, the functional changes that occur in the thalamus of vestibular migraine (VM) patients remain unknown. METHODS: In total, 28 VM patients and 28 healthy controls who were matched for age and sex underwent resting-state functional magnetic resonance imaging. They also responded to standardized questionnaires aimed at assessing the clinical features associated with migraine and vertigo. Differences in the amplitude of low-frequency fluctuation (ALFF) were analyzed and brain regions with altered ALFF in the two groups were used for further analysis of whole-brain functional connectivity (FC). The relationship between clusters and clinical features was investigated by correlation analyses. RESULTS: The ALFF in the thalamus was significantly decreased in the VM group versus the control group. In the VM group, the ALFF in the left thalamus negatively correlated with VM episode frequency. Furthermore, the left thalamus showed significantly weaker FC than both regions of the medial prefrontal cortex, both regions of the anterior cingulum cortex, the left superior/middle temporal gyrus, and the left temporal pole in the VM group. CONCLUSIONS: The thalamus plays an important role in VM patients and it is suggested that connectivity abnormalities of the thalamocortical region contribute to abnormal pain information processing and modulation, transmission, and multisensory integration in patients with VM.

One country, two systems: evidence on retirement patterns in China.

This paper documents the patterns and correlates of retirement in China using a nationally representative survey, the China Health and Retirement Longitudinal Study. After documenting stark differences in retirement ages between urban and rural residents, the paper shows that China's urban residents retire earlier than workers in many Organization for Economic Co-operation and Development countries and that rural residents continue to work until advanced ages. Differences in access to generous pensions and economic resources explain much of the urban-rural difference in retirement rates. The paper suggests that reducing disincentives created by China's Urban Employee Pension system, improving health status, providing childcare and elder care support may all facilitate longer working lives. Given spouse preferences for joint retirement, creating incentives for women to retire later may facilitate longer working lives for both men and women.