MX1 and UBE2L6 are potential metaflammation gene targets in both diabetes and atherosclerosis.

Background: The coexistence of diabetes mellitus (DM) and atherosclerosis (AS) is widespread, although the explicit metabolism and metabolism-associated molecular patterns (MAMPs) responsible for the correlation are still unclear. Methods: Twenty-four genetically wild-type male Ba-Ma mini pigs were randomly divided into five groups distinguished by different combinations of 90 mg/kg streptozotocin (STZ) intravenous injection and high-cholesterol/lipid (HC) or high-lipid (HL) diet feeding for 9 months in total. Pigs in the STZ+HC and STZ+HL groups were injected with STZ first and then fed the HC or HL diet for 9 months. In contrast, pigs in the HC+STZ and HL+STZ groups were fed the HC or HL diet for 9 months and injected with STZ at 3 months. The controls were only fed a regular diet for 9 months. The blood glucose and abdominal aortic plaque observed through oil red O staining were used as evaluation indicators for successful modelling of DM and AS. A microarray gene expression analysis of all subjects was performed. Results: Atherosclerotic lesions were observed only in the HC+STZ and STZ+HC groups. A total of 103 differentially expressed genes (DEGs) were identified as common between them. The most significantly enriched pathways of 103 common DEGs were influenza A, hepatitis C, and measles. The global and internal protein-protein interaction (PPI) networks of the 103 common DEGs consisted of 648 and 14 nodes, respectively. The top 10 hub proteins, namely, ISG15, IRG6, IRF7, IFIT3, MX1, UBE2L6, DDX58, IFIT2, USP18, and IFI44L, drive aspects of DM and AS. MX1 and UBE2L6 were the intersection of internal and global PPI networks. The expression of MX1 and UBE2L6 was 507.22 ± 342.56 and 96.99 ± 49.92 in the HC+STZ group, respectively, which was significantly higher than others and may be linked to the severity of hyperglycaemia-related atherosclerosis. Further PPI network analysis of calcium/micronutrients, including MX1 and UBE2L6, consisted of 58 and 18 nodes, respectively. The most significantly enriched KEGG pathways were glutathione metabolism, pyrimidine metabolism, purine metabolism, and metabolic pathways. Conclusions: The global and internal PPI network of the 103 common DEGs consisted of 648 and 14 nodes, respectively. The intersection of the nodes of internal and global PPI networks was MX1 and UBE2L6, suggesting their key role in the comorbidity mechanism of DM and AS. This inference was partly verified by the overexpression of MX1 and UBE2L6 in the HC+STZ group but not others. Further calcium- and micronutrient-related enriched KEGG pathway analysis supported that MX1 and UBE2L6 may affect the inflammatory response through micronutrient metabolic pathways, conceptually named metaflammation. Collectively, MX1 and UBE2L6 may be potential common biomarkers for DM and AS that may reveal metaflammatory aspects of the pathological process, although proper validation is still needed to determine their contribution to the detailed mechanism.

Current care practices for patients with Duchenne muscular dystrophy in China.

BACKGROUND: The coronavirus disease (COVID-19) pandemic has presented challenges in the care of patients with chronic diseases. We identified the challenges faced by Chinese patients with Duchenne muscular dystrophy (DMD) during the pandemic. METHODS: An online cross-sectional survey was conducted between March 27 and June 30, 2021. RESULTS: Of the 2105 valid questionnaire responses, 2,056 patients were from non-lockdown areas. In these areas, 42.8% reduced outside daily activities, 49.4% reduced rehabilitation service use, 39.7% postponed regular follow-ups, and 40.8% reported accelerated motor function decline. These figures generally increased for patients from lockdown areas-67.3% reduced outside daily activities, 44.9% reduced rehabilitation service use, 79.6% postponed regular follow-ups, and 55.1% reported accelerated motor function decline. Ambulation loss was most commonly reported in September and March before 2020; however, this trend was absent in 2020. Regarding the informed prices of disease-modifying drugs in Europe and the United States, 86.7% could afford a maximum of one-twentieth of the prices, 8.0% could afford one-tenth of the prices, and only 0.6% of the patients could afford the full prices. CONCLUSIONS: Implementation of standardized care for DMD in China is consistent with global practices, and the COVID-19 pandemic has affected the care of patients with chronic diseases worldwide, particularly in lockdown areas. Telemedicine is an effective model for providing healthcare to such patients. Healthcare workers should assist patients and establish more robust chronic disease management systems. Collaboration between governmental and non-governmental entities could address the cost of disease-modifying drugs in China and other developing countries.

Robotic laser position versus freehand in CT-guided percutaneous microwave ablation for single hepatocellular carcinoma (diameter < 3 cm): a preliminary study.

PURPOSE: To compare the accuracy and safety of robotic laser position (RLP) versus freehand for antenna CT-guided microwave ablation (MWA) of single hepatocellular carcinoma (HCC) (diameter < 3 cm). MATERIALS AND METHODS: This retrospective study was conducted between May 2020 and June 2021. A total of 40 patients with early HCC who underwent CT-guided MWA were divided into two groups: a freehand group (n = 20) and a RLP group (n = 20). Based on in-plane and out-of-plane data, the actual puncture point error (APPE), number of repositioning procedures, and operative duration were compared using the Mann-Whitney U test. Ablation-related complications were compared using the Chi-squared test. RESULTS: The mean diameter of HCC patients who received MWA was 2.4 ± 0.5 cm. For in-plane APPE, APPE was comparable between the two groups (p = 0.299). However, for the out-of-plane position, the APPE in the freehand group was higher than that in the RLP group (p = 0.027). The number of repositioning procedures was 0 (range, 0-0) for RLP-guided procedures and 3 (range, 2-5) for freehand procedures, showing a statistically significant difference between the two groups (p < 0.001). The mean operative duration for freehand procedures was 39 min, compared with 26 min for RLP-guided procedures, showing a significant difference (p = 0.013). No deaths or major complications were directly related to MWA. Minor complications in the freehand group were comparable with those in the RLP group (p = 0.313). CONCLUSION: RLP guidance significantly reduces the number of antenna repositioning procedures in MWA and improves puncture accuracy for target HCC out-of-plane. In addition, the operative duration of robotic guidance was shorter than that of freehand guidance.

Boosting reaction kinetics and reversibility in Mott-Schottky VS2/MoS2 heterojunctions for enhanced lithium storage.

Heterostructures have lately been recognized as a viable implement to achieve high-energy Li-ion batteries (LIBs) because the as-formed built-in electric field can greatly accelerate the charge transfer kinetics. Herein, we have constructed the Mott-Schottky heterostructured VS2/MoS2 hybrids with tailorable 1T/2H phase based on their matchable formation energy, which are made of metallic and few-layered VS2 vertically grown on MoS2 surface. The density functional theory (DFT) calculations unveil that such heterojunctions drive the rearrangement of energy band with a facilitated reaction kinetics and enhance the Li adsorption energy more than twice compared to the MoS2 surface. Furthermore, the VS2 catalytically expedites the Li-S bond fracture and meantime the enriched Mo6+ enables the sulfur anchoring toward the oriented reaction with Li+ to form Li2S, synergistically enhancing the reversibility of electrochemical redox. Consequently, the as-obtained VS2/MoS2 hybrids deliver a very large specific capacity of 1273 mAh g-1 at 0.1 A g-1 with 61% retention even at 5 A g-1. It can also stabilize 100 cycles at 0.5 A g-1 and 500 cycles at 1 A g-1. The findings provide in-depth insights into engineering heterojunctions towards the enhancement of reaction kinetics and reversibility for LIBs.

Treatment of knee osteoarthritis with intra-articular injection of autologous adipose-derived mesenchymal progenitor cells: a prospective, randomized, double-blind, active-controlled, phase IIb clinical trial.

OBJECTIVE: Human adipose-derived mesenchymal progenitor cells (haMPCs) are stem cells with multiple differentiation potential and immunomodulatory function. Re-Join® comprises in vitro expanded haMPCs from adipose tissue of patients combined with cell suspension solution. This study was undertaken to evaluate the efficacy and safety of Re-Join® in patients with symptomatic knee osteoarthritis (OA). METHODS: Patients with Kellgren-Lawrence grade 1-3 knee OA were recruited from two centers and randomized to receive intra-articular injection of Re-Join® or HA. Pain and function were assessed by using WOMAC score, VAS, and SF-36. Magnetic resonance imaging (MRI) analysis was performed to measure cartilage repair. Adverse events (AEs) were collected. RESULTS: Fifty-three patients were randomized. Significant improvements in WOMAC, VAS, and SF-36 scores were observed in both groups at months 6 and 12 compared with baseline. Compared with the HA group, significantly more patients achieved 50% improvement of WOMAC and a trend of more patients achieved a 70% improvement rate in Re-Join® group after 12 months. Meanwhile, there was notably more increase in articular cartilage volume of both knees in the Re-Join® group than in the HA group after 12 months as measured by MRI. AEs were comparable between two groups. Most AEs were mild and moderate except one SAE of right knee joint infection in the HA group. CONCLUSIONS: Significant improvements in joint function, pain, quality of life, and cartilage regeneration were observed in Re-Join®-treated knee OA patients with good tolerance in a period of 12 months. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02162693 . Registered 13 June 2014.

Comprehensive genetic characteristics of dystrophinopathies in China.

BACKGROUND: Dystrophinopathies are a set of severe and incurable X-linked neuromuscular disorders caused by mutations in the dystrophin gene (DMD). These mutations form a complex spectrum. A national registration network is essential not only to provide more information about the prevalence and natural history of the disease, but also to collect genetic data for analyzing the mutational spectrum. This information is extremely beneficial for basic scientific research, genetic diagnosis, trial planning, clinical care, and gene therapy. METHODS: We collected data from 1400 patients (1042 patients with confirmed unrelated Duchenne muscular dystrophy [DMD] or Becker muscular dystrophy [BMD]) registered in the Chinese Genetic Disease Registry from March 2012 to August 2017 and analyzed the genetic mutational characteristics of these patients. RESULTS: Large deletions were the most frequent type of mutation (72.2%), followed by nonsense mutations (11.9%), exon duplications (8.8%), small deletions (3.0%), splice-site mutations (2.1%), small insertions (1.3%), missense mutations (0.6%), and a combination mutation of a deletion and a duplication (0.1%). Exon 45-50 deletion was the most frequent deletion type, while exon 2 duplication was the most common duplication type. Two deletion hotspots were calculated-one located toward the central part (exon 45-52) of the gene and the other toward the 5'end (exon 8-26). We found no significant difference between hereditary and de novo mutations on deletion hotspots. Nonsense mutations accounted for 62.9% of all small mutations (197 patients). CONCLUSION: We built a comprehensive national dystrophinopathy mutation database in China, which is essential for basic and clinical research in this field. The mutational spectrum and characteristics of this DMD/BMD group were largely consistent with those in previous international DMD/BMD studies, with some differences. Based on our results, about 12% of DMD/BMD patients with nonsense mutations may benefit from stop codon read-through therapy. Additionally, the top three targets for exon-skipping therapy are exon 51 (141, 13.5%), exon 53 (115, 11.0%), and exon 45 (84, 8.0%).

Relationship between the geometry patterns of vertebrobasilar artery and atherosclerosis.

BACKGROUND: The plaques at the dorsal or lateral wall of basilar artery (BA) are associated with pontine infarcts. We sought to explore the correlations between vertebrobasilar artery geometry and BA plaque locations. METHODS: We retrospectively analyzed the imaging and clinical data of 84 patients with BA atherosclerosis. On three-dimensional time-of-flight images, a side to side diameter difference of bilateral vertebral artery (VA) and BA bending were assessed. The vertebrobasilar artery geometry was qualitatively classified into four basic configurations: Walking, Tuning Fork, Dominant-Lambda, and Hypoplasia-Lambda. On high-resolution magnetic resonance imaging, the plaques were categorized based on the involvement of the ventral, dorsal, or lateral sides of BA wall. The relationships between vertebrobasilar artery geometry parameters and plaque locations were analyzed. RESULTS: Left VA dominance was identified in 28(33%) patients, and right VA dominance in 22(26%) patients. BA bending were detected in 49 patients. There were no significant correlations between the diameter difference/ratio of VA diameters and plaque locations, or between BA bending and plaque locations. BA plaques were evenly distributed in the vertebrobasilar arteries with Tuning Fork and Dominant-Lambda configurations. In Hypoplasia-Lambda group, however, plaques were more frequently located at the dorsal wall (58.57%) than at the ventral (14.43%) and lateral wall (26.71%; P = 0.001). In Walking group, the plaques more likely occurred at the lateral (49.79%) and dorsal (35.07%) wall than at the ventral wall (14.86%, P = 0.02). CONCLUSIONS: The geometric configurations of vertebrobasilar artery strongly influence the BA plaque locations. Further prospective studies are warranted to testify whether Hypoplasia-Lambda and Walking configurations are independent risk factors for pontine infarcts.

Combining gray matter volume in the cuneus and the cuneus-prefrontal connectivity may predict early relapse in abstinent alcohol-dependent patients.

BACKGROUND: Developing more effective strategies to prevent relapse remains one of the major challenges of treating substance dependence. Previous studies have identified brain abnormalities in abstinent alcoholics. However, whether these persistent brain deficits in abstinence could predict early relapse to alcohol use has not been well established. This study aimed to identify biomarkers of relapse vulnerability by investigating persistent brain abnormalities in abstinent alcohol-dependent patients. METHODS: Brain imaging and impulsive behavior data were collected from 56 abstinent alcohol-dependent male inpatients and 33 age-matched male healthy controls. Voxel-based morphometry was used to investigate the differences of grey matter volume between the groups. The resting-state functional connectivity was examined using brain areas with gray matter deficits as seed regions. A preliminary prospective study design was used to classify patients into abstainers and relapsers after a 62-day average abstinence period. RESULTS: Compared with healthy controls, both relapsers and abstainers exhibited significantly reduced gray matter volume in the cuneus. Functional connectivity analysis revealed that relapsers relative to abstainers demonstrated increased cuneus-centered negative functional connectivity within a network of brain regions which are involved in executive control and salience. Abnormal gray matter volume in the left cuneus and the functional connectivity between the right cuneus and bilateral dorsolateral prefrontal cortex could successfully predict relapse during the 3-month follow-up period. CONCLUSIONS: Findings suggest that the abnormal gray matter volume in the cuneus and resting-state cuneus-prefrontal functional connectivity may play an important role in poor treatment outcomes in alcoholics and serve as useful neural markers of relapse vulnerability.

Altered regional and circuit resting-state activity in patients with occult spastic diplegic cerebral palsy.

BACKGROUND: Very few studies have been made to investigate functional activity changes in occult spastic diplegic cerebral palsy (SDCP). The purpose of this study was to analyze whole-brain resting state regional brain activity and functional connectivity (FC) changes in patients with SDCP. METHODS: We examined 12 occult SDCP and 14 healthy control subjects using resting-state functional magnetic resonance imaging. The data were analyzed using Resting-State fMRI Data Analysis Toolkit (REST) software. The regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF), and whole brain FC of the motor cortex and thalamus were analyzed and compared between the occult SDCP and control groups. RESULTS: Compared with the control group, the occult SDCP group showed decreased ReHo regions, including the bilateral frontal, parietal, and temporal lobes, the cerebellum, right cingulate gyrus, and right lenticular nucleus, whereas an increased ReHo value was observed in the left precuneus, calcarine, fusiform gyrus, and right precuneus. Compared with the control group, no significant differences in ALFF were noted in the occult SDCP group. With the motor cortex as the region of interest, the occult SDCP group showed decreased connectivity regions in the bilateral fusiform and lingual gyrus, but increased connectivity regions in the contralateral precentral and postcentral gyrus, supplementary motor area, and the ipsilateral postcentral gyrus. With the thalamus being regarded as the region of interest, the occult SDCP group showed decreased connectivity regions in the bilateral basal ganglia, cingulate, and prefrontal cortex, but increased connectivity regions in the bilateral precentral gyrus, the contralateral cerebellum, and inferior temporal gyrus. CONCLUSIONS: Resting-state regional brain activities and FC changes in the patients with occult SDCP exhibited a special distribution pattern, which is consistent with the pathology of the disease.

Alterations in Brain Structure and Functional Connectivity in Alcohol Dependent Patients and Possible Association with Impulsivity.

BACKGROUND: Previous studies have documented that heightened impulsivity likely contributes to the development and maintenance of alcohol use disorders. However, there is still a lack of studies that comprehensively detected the brain changes associated with abnormal impulsivity in alcohol addicts. This study was designed to investigate the alterations in brain structure and functional connectivity associated with abnormal impulsivity in alcohol dependent patients. METHODS: Brain structural and functional magnetic resonance imaging data as well as impulsive behavior data were collected from 20 alcohol dependent patients and 20 age- and sex-matched healthy controls respectively. Voxel-based morphometry was used to investigate the differences of grey matter volume, and tract-based spatial statistics was used to detect abnormal white matter regions between alcohol dependent patients and healthy controls. The alterations in resting-state functional connectivity in alcohol dependent patients were examined using selected brain areas with gray matter deficits as seed regions. RESULTS: Compared with healthy controls, alcohol dependent patients had significantly reduced gray matter volume in the mesocorticolimbic system including the dorsal posterior cingulate cortex, the dorsal anterior cingulate cortex, the medial prefrontal cortex, the orbitofrontal cortex and the putamen, decreased fractional anisotropy in the regions connecting the damaged grey matter areas driven by higher radial diffusivity value in the same areas and decreased resting-state functional connectivity within the reward network. Moreover, the gray matter volume of the left medial prefrontal cortex exhibited negative correlations with various impulse indices. CONCLUSIONS: These findings suggest that chronic alcohol dependence could cause a complex neural changes linked to abnormal impulsivity.

Diffusion tensor imaging study in Duchenne muscular dystrophy.

BACKGROUND: Duchenne muscular dystrophy (DMD) is a progressive muscle disorder associated with an intellectual deficit which is non-progressive. The aim of this study was to investigate brain microstructural changes in DMD and to explore the relationship between such changes and cognitive impairment. METHODS: All participants (12 DMD patients, 14 age-matched healthy boys), intelligence quotients (IQs) [both full (FIQ) and verbal (VIQ)] were evaluated using the Wechsler intelligence scale for children China revised (WISC-CR) edition, and brain gray matter (GM) and white matter (WM) changes were mapped using diffusion tensor imaging (DTI) with fractional anisotropy (FA). The differences between groups were analyzed using the t-test and the association of cognition with neuroimaging parameters was evaluated using Pearson's correlation coefficient. RESULTS: Compared to the normal controls, the DMD group had lower FIQ (82.0±15.39 vs. 120.21±16.06) and significantly lower splenium of corpus callosum (CC) FA values (P<0.05). Splenium of CC FA was positively correlated with VIQ (r=0.588, P=0.044). CONCLUSIONS: There were microstructural changes of splenium of CC in DMD patients, which was associated with cognitive impairment.

Manipulation of and sustained effects on the human brain induced by different modalities of acupuncture: an fMRI study.

The javascript:void(0)manipulation and sustained effects of acupuncture have been investigated in multiple studies, but several findings are inconsistent with one another. One possible explanation for these discrepancies is that different modalities of acupuncture were utilized in these studies. In the present study, we investigated both the manipulation and sustained effects of acupuncture in different modalities, including manual acupuncture (MA), electroacupuncture (EA) and transcutaneous electrical acupoint stimulation (TEAS). MA, EA, TEAS and sensory control stimulation were applied to 18 healthy subjects, and combined block-designed and resting-state fMRI scans were performed. In analyzing these data, the block-designed datasets were used to assess the manipulation effect by employing a modified general linear model. The data from the resting states, before and after stimulation, were used to explore the brain networks involved in the sustained effect. The results showed that the two 1-min stimulation periods produced similar activation patterns in the sensory control with positive activation in the sensorimotor areas and negative activation in the default mode areas. Although similar patterns could be detected in the first stimulation period in MA, EA and TEAS, no positive activation result was observed in the second stimulation period, and EA showed a more extensive deactivation compared to MA and TEAS. Additionally, all three of the modalities of acupuncture stimulation could increase the instinct brain network in rest. A more secure and spatially extended connectivity of the default mode network was observed following MA and EA, and TEAS specifically increased the functional connectivity in the sensorimotor network. The present study suggested that different brain mechanisms might be recruited in different acupuncture modalities. In addition, the findings from our work could provide methodological information for further research into the mechanism of acupuncture.