Lipid metabolism mediates the association between body mass index change and bone mineral density: The Taizhou imaging study.

BACKGROUND: Limited research explores the impact of body mass index (BMI) change on osteoporosis, regarding the role of lipid metabolism. We aimed to cross-sectionally investigate these relationships in 820 Chinese participants aged 55-65 from the Taizhou Imaging Study. METHODS: We used the baseline data collected between 2013 and 2018. T-score was calculated by standardizing bone mineral density and was used for osteoporosis and osteopenia diagnosis. Multinomial logistic regression was used to examine the effect of BMI change on bone health status. Multivariable linear regression was employed to identify the metabolites corrected with BMI change and T-score. Exploratory factor analysis (EFA) and mediation analysis were conducted to ascertain the involvement of the metabolites. RESULTS: BMI increase served as a protective factor against osteoporosis (OR = 0.79[0.71-0.88], P-value<0.001) and osteopenia (OR = 0.88[0.82-0.95], P-value<0.001). Eighteen serum metabolites were associated with both BMI change and T-score. Specifically, high-density lipoprotein (HDL) substructures demonstrated negative correlations (ß = -0.08 to -0.06 and - 0.12 to -0.08, respectively), while very low-density lipoprotein (VLDL) substructions showed positive correlations (ß = 0.09 to 0.10 and 0.10 to 0.11, respectively). The two lipid factors (HDL and VLDL) extracted by EFA acted as mediators between BMI change and T-score (Prop. Mediated = 8.16% and 10.51%, all P-value<0.01). CONCLUSION: BMI gain among Chinese aged 55-65 is beneficial for reducing the risk of osteoporosis. The metabolism of HDL and VLDL partially mediates the effect of BMI change on bone loss. Our research offers novel insights into the prevention of osteoporosis, approached from the perspective of weight management and lipid metabolomics.

Mobility-related brain regions linking carotid intima-media thickness to specific gait performances in old age.

BACKGROUND: Gait disturbance is common in older adults with vascular diseases. However, how carotid atherosclerosis affects gait remains poorly understood. The objectives were to investigate the associations between carotid intima-media thickness and specific gait performances and explore the potential role of brain structure in mediating these associations. METHODS: A cross-sectional analysis of data from the Taizhou Imaging Study was conducted, including 707 individuals who underwent both gait and carotid ultrasound examinations. Gait assessments include the Timed-Up-and-Go test, the Tinetti test, and quantitative gait assessment using a wearable device. Quantitative parameters were summarized into independent gait domains with factor analysis. Magnetic resonance images were obtained on a 3.0-Tesla scanner, and the volumes of fifteen brain regions related to motor function (primary motor, sensorimotor), visuospatial attention (inferior posterior parietal lobules, superior posterior parietal lobules), executive control function (dorsolateral prefrontal cortex, anterior cingulate), memory (hippocampus, entorhinal cortex), motor imagery (precuneus, parahippocampus, posterior cingulated cortex), and balance (basal ganglia: pallidum, putamen, caudate, thalamus) were computed using FreeSurfer and the Desikan-Killiany atlas. Mediation analysis was conducted with carotid intima-media thickness as the predictor and mobility-related brain regions as mediators. RESULTS: Carotid intima-media thickness was found to be associated with the Timed-Up-and-Go performance (ß = 0.129, p = 0.010) as well as gait performances related to pace (ß=-0.213, p < 0.001) and symmetry (ß = 0.096, p = 0.045). Besides, gait performances were correlated with mobility-related brain regions responsible for motor, visuospatial attention, executive control, memory, and balance (all FDR < 0.05). Notably, significant regions differed depending on the gait outcomes measured. The primary motor (41.9%), sensorimotor (29.3%), visuospatial attention (inferior posterior parietal lobules, superior posterior parietal lobules) (13.8%), entorhinal cortex (36.4%), and motor imagery (precuneus, parahippocampus, posterior cingulated cortex) (27.3%) mediated the association between increased carotid intima-media thickness and poorer Timed-Up-and-Go performance. For the pace domain, the primary motor (37.5%), sensorimotor (25.8%), visuospatial attention (12.3%), entorhinal cortex (20.7%), motor imagery (24.9%), and balance (basal ganglia: pallidum, putamen, caudate, thalamus) (11.6%) acted as mediators. CONCLUSIONS: Carotid intima-media thickness is associated with gait performances, and mobility-related brain volume mediates these associations. Moreover, the distribution of brain regions regulating mobility varies in the different gait domains. Our study adds value in exploring the underlying mechanisms of gait disturbance in the aging population.

Spectral CT - a new supplementary method for preoperative assessment of pathological grades of esophageal squamous cell carcinoma.

BACKGROUND: Spectral CT imaging parameters have been reported to be useful in the differentiation of pathological grades in different malignancies. This study aims to investigate the value of spectral CT in the quantitative assessment of esophageal squamous cell carcinoma (ESCC) with different degrees of differentiation. METHODS: There were 191 patients with proven ESCC who underwent enhanced spectral CT from June 2018 to March 2020 retrospectively enrolled. These patients were divided into three groups based on pathological results: well differentiated ESCC, moderately differentiated ESCC, and poorly differentiated ESCC. Virtual monoenergetic 40 keV-equivalent image (VMI40keV), iodine concentration (IC), water concentration (WC), effective atomic number (Eff-Z), and the slope of the spectral curve(λHU) of the arterial phase (AP) and venous phase (VP) were measured or calculated. The quantitative parameters of the three groups were compared by using one-way ANOVA and pairwise comparisons were performed with LSD. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance of these parameters in poorly differentiated groups and non-poorly differentiated groups. RESULTS: There were significant differences in VMI40keV, IC, Eff-Z, and λHU in AP and VP among the three groups (all p < 0.05) except for WC (p > 0.05). The VMI40keV, IC, Eff-Z, and λHU in the poorly differentiated group were significantly higher than those in the other groups both in AP and VP (all p < 0.05). In the ROC analysis, IC performed the best in the identification of the poorly differentiated group and non-poorly differentiated group in VP (AUC = 0.729, Sensitivity = 0.829, and Specificity = 0.569 under the threshold of 21.08 mg/ml). CONCLUSIONS: Quantitative parameters of spectral CT could offer supplemental information for the preoperative differential diagnosis of ESCC with different degrees of differentiation.

The gut microbiome in subclinical atherosclerosis: a population-based multiphenotype analysis.

OBJECTIVES: An altered microbiota, which can be described quantitatively, has been identified as playing a pivotal role in host vascular physiology, and it may contribute to various diseases. The aim of this study was to better understand the role of the gut microbiota in vascular physiology in a subclinical elderly population, and to investigate how lifestyle affects the composition of host gut microbiota to further impact the pathogenesis of vascular diseases. METHODS: We performed a population-based faecal metagenomic study over 569 elderly asymptomatic subclinical individuals in rural China. An association network was built based on clinical measurements and detailed epidemiologic questionnaires, including blood chemistry, arterial stiffness, carotid ultrasonography, and metagenomic datasets. RESULTS: By analyzing the breadth, depth and impact of each node of the association network, we found carotid arterial atherosclerosis indices, including intima-media thickness (IMT), were essential in the network, and were significantly associated with living habits, socio-economic status, and diet. Using mediation analysis, we found that higher frequency of eating fresh fruits and vegetables, and more exercise significantly reduced carotid atherosclerosis in terms of IMT, peak systolic velocity and end-diastolic velocity values through the mediation of Alistepes, Oligella and Prevotella. Gut microbes explained 16.5% of the mediation effect of lifestyle on the pathogenesis of carotid atherosclerosis. After adjustment, Faecalicatena [odds ratio (OR) = 0.12 ∼0.65] was shown to be protective against the formation of carotid atherosclerosis, independently, while Libanicoccus (OR = 1.46 ∼4.20 ) was associated with increased carotid arterial IMT. KEGG/KO Kyoto Encyclopedia of Genes and Genomes/ KEGG Orthology (KEGG/KO) analyses revealed a loss of anti-inflammation function in IMT subjects. CONCLUSION: Our study revealed a Chinese population-wide phenotype-metagenomic association network and a mediation effect of gut microbiota on carotid artery atherosclerosis, hinting at potential therapeutic and preventive uses for microbiota in vascular diseases.

Lifestyle, multi-omics features, and preclinical dementia among Chinese: The Taizhou Imaging Study.

China has the largest number of patients with dementia in the world. However, dementia in the Chinese population is still poorly understood and under-researched. Given the differences in genetic, demographic, sociocultural, lifestyle, and health profiles among Chinese and other ethnic/racial groups, it is crucial to build appropriate infrastructure for long-term longitudinal studies to advance Chinese cognitive aging and dementia research. We initiated a community-based prospective cohort-the Taizhou Imaging Study (TIS)-to accelerate the understanding of dementia and cerebrovascular diseases in Chinese. This article presents the rationale, aims, study design, and organization of TIS. In addition, we described some examples of the types of studies such a resource might support. The TIS provides a new framework for facilitating Chinese dementia research, encompassing invaluable resources including detailed epidemiological, sociocultural, neuroimaging, and omics data.

Diagnostic significance of magnetic resonance imaging in patients with cervical cancer after brachytherapy: a meta-analysis.

BACKGROUND: Patients with uterine cervical cancer suffer high mortality. Accurate detection of a residual tumor by magnetic resonance imaging (MRI) during and after directed brachytherapy (BCT) is crucial for the success of cancer treatment and is a significant predictor of patient survival. PURPOSE: To determine the diagnostic significance of MRI in detecting residual tumor tissue after BCT. MATERIAL AND METHODS: The Web of Knowledge, Cochrane Library, and PubMed were systematically searched (January 1997 to December 2016) for post-brachytherapy MRI studies that measured residual tumors in patients with uterine cervical cancer. All data were analyzed using the Meta-Disc 1.4 program. RESULTS: Four clinical studies consisting of 163 patients (147 of whom were included in the present analysis) who were diagnosed with uterine cervical cancer according to the International Federation of Gynecology and Obstetrics (FIGO) staging system were included in the study. All the patients received BCT and underwent MRI detection of residual tumors tissue. In studies where the accuracy of MRI detection was confirmed by histological tests or gynecological tests, the summary estimates of specificity, sensitivity, positive predictive value, negative predictive value, and accuracy were 88.5%, 83.5%, 53.5%, 97.1%, and 84.3%, respectively. CONCLUSION: MRI-directed BCT is commonly used for cervical cancer patients. Based on our investigation of four independent studies, MRI showed better prediction of positive results than negative results in patients with cervical cancer after BCT. However, more data on the greater numbers of patients are needed to establish the accuracy of MRI detection of cervical cancer after BCT.

Low Bone Mineral Density Is Not Associated with Subclinical Atherosclerosis: A Population-Based Study in Rural China.

OBJECTIVES: Loss of bone mass may affect the progression of atherosclerosis. We investigated the relationship between low bone mineral density (BMD) and subclinical atherosclerosis in rural China. METHODS: In total, 333 men and 421 postmenopausal women aged 55-65 years were enrolled. BMD was measured in the lumbar spine, femoral neck, and total hip using dual-energy X-ray absorptiometry. Subclinical atherosclerosis was defined as increased carotid artery intima-media thickness (CIMT ≥0.9 mm), the presence of carotid plaques, high brachial-ankle pulse wave velocity (baPWV ≥1,400 cm/s), and low ankle-brachial index (ABI ≤1). Binary logistic regression analyses were used to estimate the association between low BMD and subclinical atherosclerosis. RESULTS: There was no significant difference in BMD between the normal group and the subclinical atherosclerosis group. After full adjustment for the relevant covariates, a boundary significant association was found between low BMD in the femoral neck and baPWV in postmenopausal women (odds ratio = 1.77, p = 0.049). After full adjustment, neither BMD nor low BMD were significantly associated with subclinical atherosclerosis in men or postmenopausal women. CONCLUSIONS: Low BMD is not associated with subclinical atherosclerosis in Chinese individuals aged 55-65 years resident in rural China.

Value of Diffusion-Weighted Magnetic Resonance Imaging Combined with miR-18a Level in Predicting Radiosensitivity of Cervical Cancer.

BACKGROUND Radioresistance during radiotherapy of cervical cancer often leads to treatment failure; therefore, there is an urgent need to develop effective predictive indicators of radiosensitivity for cervical cancer patients. MATERIAL AND METHODS Cervical cancer cells were collected from 40 patients who received surgical resections. The relationships between apparent diffusion coefficient (ADC) values of masses before surgery and different micro-RNAs (miRNA) levels (miR-18a, miR-132, and miR-145) of these cells were investigated. Cervical cancer cells were divided into 4 groups according to the ADC values of original tumor tissues and expression level of miR-18a. Then, these cells were exposed with irradiation both in vitro and in vivo. RESULTS Advanced cervical cancer showed lower ADC values in magnetic resonance imaging. miR-18a, miR-132, and miR-145 all were increased in the cervical cancer tissues, while miR-18a showed a more marked negative correlation with ADC values. The results of in vitro and in vivo assays showed that higher expression of miR-18a in cervical cancer cells leads to more radiosensitivity, especially in cells from cancer tissues with lower ADC values. CONCLUSIONS The combination of ADC values with expression level of miR-18a may be a new and reliable predictor for radiosensitivity of cervical cancer, helping cervical cancer patients with low ADC values and high expressions of miR-18a to achieve better outcomes in radiotherapy.

An MRI-based feasibility study of unilateral percutaneous vertebroplasty.

BACKGROUND: Percutaneous vertebroplasty (PVP) has been demonstrated to be effective in the treatment of osteoporotic fracture. The bilateral pedicular approach is the most frequently used method. However, unilateral PVP is becoming increasingly more attractive for surgeons because of its numerous benefits, including lower radiation exposure, less tissue injury, and less bone cement leakage. The purpose of this study was to investigate the anatomical feasibility of unilateral PVP by exploring the differences in the puncture success rate of the unilateral pedicular approach among different lumbar segments, between men and women, and between the left and right sides. METHODS: Punctures were simulated on magnetic resonance imaging scans of 200 patients (100 men, 100 women) at a maximum angle via a pedicular approach. The distance between the entry point and the midline of the vertebral body, the maximum puncture angle, the puncture success value, and the puncture success rate were measured and compared among different lumbar levels, between the two sexes, and between the left and right sides. RESULTS: The maximum puncture distance between the entry point and the midline gradually increased from L1 to L5, and the maximum puncture angle showed the same tendency from L1 to L5. The puncture success values for L3 and L4 were higher than those for the other lumbar levels (L1, 31.53 ± 34.45; L2, 42.15 ± 28.06; L3, 56.21 ± 18.30; L4, 56.20 ± 12.93; and L5, 48.01 ± 6.88). The puncture success rates varied from 69.5 to 98.0 % among the different lumbar levels; L3 and L4 were the two highest (L3, 95.5 %; L4, 98.0 %). There were significant differences in these measurements between men and women and between the left and right sides. CONCLUSIONS: PVP with the unilateral puncture approach appears more likely to succeed at L3 to L5 than at L1 and L2. The unilateral approach might be more suitable for men than women at levels other than L5. Additionally, the left pedicular approach might be optimal for unilateral PVP procedures.

Brain white matter microstructural alterations in patients with systemic lupus erythematosus: an automated fiber quantification study.

This study aimed to identify damaged segments of brain white matter fiber tracts in patients with systemic lupus erythematosus (SLE) using diffusion tensor imaging (DTI)-based automated fiber quantification (AFQ), and analyze their relationship with cognitive impairment. Clinical and imaging data for 39 female patients with SLE and for 44 female healthy controls (HCs) were collected. AFQ was used to track whole-brain white matter tracts in each participant, and each tract was segmented into 100 equally spaced nodes. DTI metrics including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated at each node. Correlations were also explored between DTI metrics in the damaged segments of white matter fiber tracts and neuropsychological test scores of patients with SLE. Compared with HCs, SLE patients exhibited significantly lower FA values, and significantly higher MD, AD, RD values in many white matter tracts (all P < 0.05, false discovery rate-corrected). FA values in nodes 97-100 of the left inferior fronto-occipital fasciculus (IFOF) positively correlated with the mini-mental state examination score. AFQ enables precise and accurate identification of damage to white matter fiber tracts in brains of patients with SLE. FA values in the left IFOF correlate with cognitive impairment in SLE.

Bidirectional mediation of bone mineral density and brain atrophy on their associations with gait variability.

This mediation analysis aimed to investigate the associations among areal bone mineral density, mobility-related brain atrophy, and specific gait patterns. A total of 595 participants from the Taizhou Imaging Study, who underwent both gait and bone mineral density measurements, were included in this cross-sectional analysis. We used a wearable gait tracking device to collect quantitative gait parameters and then summarized them into independent gait domains with factor analysis. Bone mineral density was measured in the lumbar spine, femoral neck, and total hip using dual-energy X-ray absorptiometry. Magnetic resonance images were obtained on a 3.0-Tesla scanner, and the volumes of brain regions related to mobility were computed using FreeSurfer. Lower bone mineral density was found to be associated with higher gait variability, especially at the site of the lumbar spine (ß = 0.174, FDR = 0.001). Besides, higher gait variability was correlated with mobility-related brain atrophy, like the primary motor cortex (ß = 0.147, FDR = 0.006), sensorimotor cortex (ß = 0.153, FDR = 0.006), and entorhinal cortex (ß = 0.106, FDR = 0.043). Bidirectional mediation analysis revealed that regional brain atrophy contributed to higher gait variability through the low lumbar spine bone mineral density (for the primary motor cortex, P = 0.018; for the sensorimotor cortex, P = 0.010) and the low lumbar spine bone mineral density contributed to higher gait variability through the primary motor and sensorimotor cortices (P = 0.026 and 0.010, respectively).

Unraveling the role of serum metabolites in the relationship between plant-based diets and bone health in community-dwelling older adults.

The potential adverse effects of the plant-based dietary pattern on bone health have received widespread attention. However, the biological mechanisms underlying the adverse effects of plant-based diets on bone health remain incompletely understood. The objective of this study was to identify potential biomarkers between plant-based diets and bone loss utilizing metabolomic techniques in the Taizhou Imaging Study (TIS) (N = 788). Plant-based diet indexes (overall plant-based diet index (PDI), healthy plant-based diet index (hPDI), and unhealthy plant-based diet index (uPDI)) were calculated using the food frequency questionnaire, and bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry. A multinomial logistic regression was used to explore the associations of plant-based diet indexes with bone loss. Furthermore, mediation analysis and exploratory factor analysis (EFA) were performed to explore the mediated effects of metabolites on the association of plant-based diets with BMD T-score. Our results showed that higher hPDI and uPDI were positively associated with bone loss. Moreover, nineteen metabolites were significantly associated with BMD T-score, among them, seven metabolites were associated with uPDI. Except for cholesterol esters in VLDL-1, the remaining six metabolites significantly mediated the negative association between uPDI and BMD T-score. Interestingly, we observed that the same six metabolites mediated the positive association between fresh fruit and BMD T-score. Collectively, our results support the deleterious effects of plant-based diets on bone health and discover the potential mediation effect of metabolites on the association of plant-based diets with bone loss. The findings offer valuable insights that could optimize dietary recommendations and interventions, contributing to alleviate the potential adverse effects associated with plant-based diets.

Clinical Value of COVID-19 Chest Radiography and High-Resolution CT Examination.

BACKGROUND: Novel coronavirus disease 2019 (COVID-19) pneumonia remains a matter of concern. Chest CT findings of COVID-19 pneumonia have been reported widely, while there is relatively rare research on chest X-ray (CXR). OBJECTIVE: The study was aimed to compare the CXR and chest CT findings of patients with confirmed COVID-19 infection and to explore their respective clinical values. METHODS: 28 inpatients with COVID-19 pneumonia who underwent both CXR and CT were included. The pulmonary manifestations of the lesions were recorded. Ground-glass opacity (GGO), consolidation, and fibrosis were quantified in CXR and chest CT separately. Consistency was analyzed using Fleiss' kappa and intraclass correlation coefficient. The stages of the disease in CXR and chest CT were evaluated. RESULTS: Approximately 67.9% (19/28) of subjects had abnormal findings on CXR. The common manifestations in CXR were ground-glass opacities (GGO) (100%, 19/19) and consolidation (68.4%, 13/19). 92.9% (26/28) of patients had abnormal manifestations on CT. The common manifestations in CT were GGO (88.5%, 23/26), consolidation (69.2%, 18/26), reticular opacity (69.2%, 18/26) and nodule (46.2%, 12/26). Among the abnormalities between CXR and CT, only consolidation was consistent (κ=0.510). GGO (ICC=0.501) and consolidation (ICC=0.431) scores were consistent in CXR and chest CT. The results of staging were the same in 14 cases, most of them were in stage I and stage II. While in other cases with inconsistent results, CT was more advanced in the disease stage than CXR, mainly stage III and stage IV. CONCLUSION: CXR is helpful to observe the change of the pulmonary lesions in patients with confirmed COVID-19 pneumonia. CT can be used for early diagnosis and staging of lesions.

Application of dual-energy computed tomography in preoperative evaluation of Ki-67 expression levels in solid non-small cell lung cancer.

To investigate whether there were significant differences in dual-energy CT (DECT) in reflecting different quantitative parameters among different levels of Ki-67 expression in patients with solid non-small cell lung cancer (NSCLC). The diagnosis performance of DECT in patients with solid lung adenocarcinoma (LAC) among NSCLC was further discusses. Two hundred fifteen patients confirmed with solid NSCLC were enrolled and analyzed retrospectively in this study. 148 patients were confirmed with LAC among all patients. Three expression levels of Ki-67 were determined by the percentage of Ki-67 positive cancer cells with immunohistochemistry: high-level group (>30%), middle-level group (10%-30%), and low-level group (≤10%). And the latter two levels also known as non-high-level group. The quantitative parameters of enhanced chest DECT (venous phase, VP), including iodine concentration (IC), water concentration (WC), CT value at 40 keV (CT40keV), the slope of energy spectral attenuation curve (λHU) and normalized iodine concentration (NIC) were measured and calculated by gemstone spectral imaging Viewer software. One-way ANOVA was used for the comparison of normal distribution DECT parameters between three levels for patients with NSCLC and patients with LAC. Non-normal distribution data were tested by non-parametric test. In addition, the receiver operating characteristic curve of statistically significant DECT parameters was drawn to distinguish the non-high-level and the high-level of Ki-67. Area under the curve (AUC), sensitivity, specificity was calculated to measure the diagnostic performance of parameter. Both in solid NSCLC and LAC, the IC, NIC, WC, λHU and CT40keV at VP in the high-level group were significantly lower than those in the middle- and low-level group respectively, and the WC at VP in the high-level group was significantly higher than that in the middle- and low-level group respectively (all P < .05). Receiver operating characteristic analysis showed that IC and λHU at VP performed better in distinguishing the high-level and the non-high-level of Ki-67 (NSCLC: AUC = 0.713 and 0.714 respectively; LAC: AUC = 0.705 and 0.706 respectively). Quantitative parameters of DECT provide a new non-invasive method for evaluating the proliferation of cancer cells in solid NSCLC and LAC.

Alterations in degree centrality and cognitive function in breast cancer patients after chemotherapy.

The goal of this study was to determine the presence or absence of persistent functional impairments in specific brain regions in breast cancer patients during the recovery period after chemotherapy. We calculated degree centrality (DC) and explored the correlation between brain changes and cognitive scores in 29 female patients with breast cancer who had completed chemotherapy within 1-6 years (C + group) and in 28 age-matched patients with breast cancer who did not receive chemotherapy (C- group). All patients underwent rs-fMRI and cognitive testing. Differences in brain functional activity were explored using DC parameters. Correlations between brain features and cognitive scores were analyzed via correlation analysis. Compared with the C- group, the C + group obtained significantly lower motor and cognitive subscores on the Fatigue Scale for Motor and Cognitive Functions and four subscale scores of the Functional Assessment of Cancer Therapy-Cognitive Function (P < 0.05). Furthermore, the C + group exhibited a significantly higher DC z-score (zDC) in the right superior temporal gyrus and left postcentral gyrus (P < 0.01, FWE-corrected), and a lower zDC in the left caudate nucleus (P < 0.01, FWE-corrected). We found a positive correlation between digit symbol test (DST) scores and zDC values in the right superior temporal gyrus (r = 0.709, P < 0.001), and a negative correlation between DST scores and zDC values in the right angular gyrus (r = -0.784, P < 0.001) and left superior parietal gyrus (r = -0.739, P < 0.001). Chemotherapy can cause abnormal brain activity and cognitive decline in patients with breast cancer, and these effects are likely to persist. DC can be used as an imaging marker for chemotherapy-related cognitive impairment after chemotherapy in breast cancer patients.

Co-Delivery of Paclitaxel Prodrug, Gemcitabine and Porphine by Micelles for Pancreatic Cancer Treatment via Chemo-Photodynamic Combination Therapy.

Pancreatic carcinoma is an aggressive subtype of cancer with poor prognosis, known for its refractory nature. To address this challenge, we have established a stable nanoplatform that combines chemotherapy with photodynamic therapy (PDT) to achieve better curative efficacy. First, we designed and synthesized a disulfide-bonded paclitaxel (PTX)-based prodrug, which was further mixed with gemcitabine (GEM) and photosensitizer THPP in an optimized ratio. Subsequently, the mixture was added dropwise into amphiphilic polymer DSPE-PEG water solution to form micelles composed of DSPE-PEG nanoparticles (TPG NPs). The TPG NPs were around 135 nm, and showed great ability of DTT stimulated release of PTX and GEM. Moreover, the TPG NPs can be efficiently uptaken by pancreatic cancer PANC-1 cells and effectively kill them, especially when combined with 650 nm laser irradiation. Finally, the TPG NPs have shown enhanced long-term circulation ability and also exhibited efficient anti-tumor activity in combination with 650 nm laser irradiation in a pancreatic cancer mouse model. In summary, the designed TPG NPs possesses great potential for co-delivery of paclitaxel prodrug, GEM and THPP, which enables combined chemo-photodynamic therapy for cancer treatment. In addition, the stimulated release of PTX prodrug and GEM also allows for better targeting of tumor cells and the increased therapeutic effect against cancer cells. Overall, the TPG NPs can serve as a good candidate for pancreatic cancer treatment.

The Effects of Brain Magnetic Resonance Imaging Indices in the Association of Olfactory Identification and Cognition in Chinese Older Adults.

Background: Olfactory identification dysfunction frequently occurs in individuals with cognitive decline; however, a pathological mechanism linking the two has not been discovered. We aimed to study the association between olfactory identification and cognitive function, and determine the effects of brain regions atrophy therein. Methods: A total of 645 individuals (57.5% were female) from the Taizhou Imaging Study, who underwent cognitive and olfactory identification measurements, were included. A subsample of participants underwent brain magnetic resonance imaging (n = 622). Cognition was assessed with a neuropsychological battery. Olfactory identification was measured using a 12-item Sniffin' Sticks test. Beta and logistic regressions were used to elucidate the association between olfactory identification and cognition, and the effects of brain regions atrophy in this association. Results: Dementia was diagnosed in 41 (6.4%) individuals (mean age = 64.8 years), and mild cognitive impairment (MCI) in 157 (24.3%) individuals (mean age = 64.4 years). Olfactory identification was associated with MMSE and MoCA (both P < 0.001) and specific cognitive domains (memory, executive function, visuospatial function, and language; all P < 0.05). Higher olfactory identification was associated with lower likelihood of MCI and dementia (P < 0.05). The amygdala volume was significantly related to olfactory identification, MMSE, MoCA, and language, and could attenuate the association between olfactory identification and cognitive function. Conclusion: The association between olfactory identification and cognition can be partly attributable to differences in amygdala volume, suggesting that the amygdala could be a shared neural substrate that links olfactory identification and cognitive function. Limitations of this study include that all these results were based on a cross-sectional study.

Cross-sectional associations between cortical thickness and independent gait domains in older adults.

BACKGROUND: Although the prevalence of gait disturbance is increasing with population aging, our understanding of its underlying neural basis is still limited. The precise brain regions linked to specific gait domains have not been well defined. In this study, we aim to investigate the associations of cortical thickness and different gait domains, and to explore whether these associations could be explained by cerebral small vessel disease. METHODS: A total of 707 community-dwelling participants from the Taizhou Imaging Study (mean age: 60.2 ± 3.0 years, 57.4% female) were involved. All participants underwent brain MRI and gait assessment. We obtained quantitative gait parameters using wearable devices and then summarized them into three independent gait domains through factor analysis. Cortical thickness was analyzed and visualized using FreeSurfer and Surfstat. RESULTS: Three independent domains (pace, rhythm, and variability) were summarized from 12 gait parameters. Among gait domains, poorer pace was associated with the thinner cortical thickness of multiple regions, which included areas related with motor function (e.g., the primary motor cortex, premotor cortex, and supplementary motor area), sensory function (e.g., the postcentral gyrus and paracentral lobule), visuospatial attention (e.g., the lateral occipital cortex and lingual gyrus), and identification and cognition (e.g., the fusiform gyrus and entorhinal cortex). Such a relationship was only slightly attenuated after adjustment for cerebrovascular risk factors and cerebral small vessel disease. No statistically significant association was found between cortical thickness and the rhythm or variability domains. CONCLUSIONS: Poorer pace is independently associated with thinner cortical thickness in areas important for motor, sensory, cognitive function, and visuospatial attention. Our study emphasizes the importance of cortical thickness in gait control and adds value in investigating neural mechanisms of gait.

Associations between serum metabolites and subclinical atherosclerosis in a Chinese population: the Taizhou Imaging Study.

Metabolomics provides a promising tool for understanding the pathophysiology and identifying biomarkers of atherosclerosis. We aimed to estimate the associations between circulating metabolites and subclinical atherosclerosis in a Chinese cohort. The baseline serum levels of 38 metabolites of 489 individuals were measured using nuclear magnetic resonance. Associations between metabolites and brachial-ankle pulse wave velocity (baPWV) and carotid intima-media thickness (IMT) were determined using a linear regression. A multivariate logistic regression was used to evaluate the associations of metabolites and subclinical atherosclerosis defined as high baPWV (>median) and increased IMT (>median). After adjusting for covariates and multiple testing corrections (false discovery rate; FDR), two branched-chain amino acids (BCAAs; leucine and isoleucine), one ketone (acetoacetate), and two lipids were positively associated with baPWV. Lactate was inversely associated with IMT. Elevated acetoacetate levels (odds ratio: 1.53, 95% confidence interval: 1.20-1.97; FDR <0.001) and four other lipid features were associated with an increased risk of high baPWV. Alterations in circulating lipids and BCAAs were associated with the risk of arterial stiffness in the middle-aged Chinese population. Our findings provide clues to understanding the potential mechanisms of subclinical atherosclerosis; however, further validation in a broader population context and the exploration of potential clinical applications are warranted.

Total Cerebral Small Vessel Disease Burden Is Related to Worse Performance on the Mini-Mental State Examination and Incident Dementia: A Prospective 5-Year Follow-Up.

Individual cerebral small vessel disease (CSVD) may cause cognitive decline. However, the association between total burden of CSVD and cognitive deterioration in the general population remains unclear. We aimed to determine whether total CSVD score is associated with cognitive performance change and incident dementia in the general population. In the longitudinal population-based Taizhou Imaging Study, 556 participants free of neurological disorders underwent brain MRI and neuropsychological testing at baseline. A total of 456 participants were followed up for cognitive performance for a mean (standard deviation) of 4.6 (0.6) years. Total CSVD score (range 0-4) was calculated by assigning 1 point for the presence of each of the following markers: lacune, white matter hyperintensity, cerebral microbleed, and perivascular space. Beta regression was used to evaluate the association between total CSVD burden and MMSE score change. The association of prevalent CSVD with incident dementia was studied using Fisher's exact test. CSVDs were present in 262 individuals (47.1%). The total CSVD score was significantly associated with MMSE score decline (p = 0.001). Compared to those with no CSVD, participants with 4 CSVD markers had a steeper decline in MMSE score (ß: -0.53, 95% CI: -0.86 to -0.21; p = 0.001). A total of 15 participants developed dementia during follow-up. The presence of more than three CSVD markers at baseline was associated with a significantly higher risk of dementia (p = 0.020). Total CSVD burden appears to be associated with MMSE score decline and incident dementia in a general population in China.