Diagnostic Implications of Ultrasound Evaluation in Patients With Shoulder Impingement Syndrome.

OBJECTIVE: To evaluate the diagnostic value of musculoskeletal ultrasound measurements of subacromial bursa (SAB) thickness, supraspinatus tendon (SUP) thickness, acromiohumeral distance (AHD), and SUP-to-AHD ratio (AHD%) in patients with shoulder impingement syndrome (SIS). METHODS: This was a prospective cross-sectional observational study. Thirty patients with SIS (60 shoulders) admitted between January 2019 and January 2020 were enrolled. The SUP thickness, SAB thickness, AHD, and AHD% (calculated as AHD% = [(SUP / AHD) × 100%]) were measured in 60 shoulders using musculoskeletal ultrasound. RESULTS: The affected shoulder displayed thicker SUP and SAB (t = 7.838), narrower AHD (t = 2.324), and larger AHD% (t = 6.875) than the unaffected shoulder (P < .05). The SUP thickness showed a linear positive correlation with AHD (r = .503) and AHD% (r = .792) in the affected shoulder (P < .05). On receiver operating characteristic analysis, AHD*AHD% showed the best diagnostic performance in both measurements (area under the curve: 0.877). CONCLUSION: This study revealed that SIS symptoms may be related to a larger AHD% with SUP thickening. As diagnostic criteria, the cut-off values of AHD% (65.6%) and AHD*AHD% (0.504) have good sensitivity and specificity and can help improve the differential diagnosis of patients with SIS.

RIPK1 polymorphisms and expression levels: impact on genetic susceptibility and clinical outcome of epithelial ovarian cancer.

BACKGROUND: The aim of this study was to explore the associations of RIPK1 polymorphisms, plasma levels and mRNA expression with susceptibility to epithelial ovarian cancer (EOC) and clinical outcome. METHODS: Three hundred and nineteen EOC patients included in a 60-month follow-up program and 376 controls were enrolled. Two tag SNPs (rs6907943 and rs9392453) of RIPK1 were genotyped using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. Plasma levels of RIPK1 and RIPK1 mRNA expression in white blood cells were determined by ELISA and qPCR, respectively. RESULTS: For rs9392453, significantly increased EOC risk was found to be associated with C allele (P = 0.002, OR = 1.49, 95%CI 1.15-1.92), and with CT/CC genotypes in the dominant genetic model (P = 0.006, OR = 1.54, 95%CI 1.12-2.08). CC haplotype (rs6907943-rs9392453) was associated with increased EOC susceptibility. CC genotype of rs6907943 and CT/CC genotypes of rs9392453 were associated with early onset (age ≤ 50 years) of EOC (OR = 2.5, 95%CI 1.03-5.88, and OR = 1.64, 95%CI 1.04-2.63, respectively). AC genotype of rs6907943 was associated with better overall survival of EOC patients in the over-dominant genetic model (P = 0.035, HR = 0.41, 95%CI 0.18-0.94). Multivariate survival analysis identified the AC genotype of rs6907943 as an independent protective factor for survival of early onset patients (P = 0.044, HR = 0.12, 95%CI 0.02-0.95). Compared to controls, significantly increased plasma levels of RIPK1 and reduced RIPK1 mRNA expression were observed in patients. CONCLUSIONS: Our results suggest that tag SNPs of RIPK1, increased plasma levels of RIPK1 protein and reduced RIPK1 mRNA expression in white blood cells, may influence the susceptibility to EOC. SNP rs6907943 may be a useful marker to distinguish EOC patients with high risk of death.

BMECs Ameliorate High Glucose-Induced Morphological Aberrations and Synaptic Dysfunction via VEGF-Mediated Modulation of Glucose Uptake in Cortical Neurons.

It has been demonstrated that diabetes cause neurite degeneration in the brain and cognitive impairment and neurovascular interactions are crucial for maintaining brain function. However, the role of vascular endothelial cells in neurite outgrowth and synaptic formation in diabetic brain is still unclear. Therefore, present study investigated effects of brain microvascular endothelial cells (BMECs) on high glucose (HG)-induced neuritic dystrophy using a coculture model of BMECs with neurons. Multiple immunofluorescence labelling and western blot analysis were used to detect neurite outgrowth and synapsis formation, and living cell imaging was used to detect uptake function of neuronal glucose transporters. We found cocultured with BMECs significantly reduced HG-induced inhibition of neurites outgrowth (including length and branch formation) and delayed presynaptic and postsynaptic development, as well as reduction of neuronal glucose uptake capacity, which was prevented by pre-treatment with SU1498, a vascular endothelial growth factor (VEGF) receptor antagonist. To analyse the possible mechanism, we collected BMECs cultured condition medium (B-CM) to treat the neurons under HG culture condition. The results showed that B-CM showed the same effects as BMEC on HG-treated neurons. Furthermore, we observed VEGF administration could ameliorate HG-induced neuronal morphology aberrations. Putting together, present results suggest that cerebral microvascular endothelial cells protect against hyperglycaemia-induced neuritic dystrophy and restorate neuronal glucose uptake capacity by activation of VEGF receptors and endothelial VEGF release. This result help us to understand important roles of neurovascular coupling in pathogenesis of diabetic brain, providing a new strategy to study therapy or prevention for diabetic dementia. Hyperglycaemia induced inhibition of neuronal glucose uptake and impaired to neuritic outgrowth and synaptogenesis. Cocultured with BMECs/B-CM and VEGF treatment protected HG-induced inhibition of glucose uptake and neuritic outgrowth and synaptogenesis, which was antagonized by blockade of VEGF receptors. Reduction of glucose uptake may further deteriorate impairment of neurites outgrowth and synaptogenesis.

CD8A is a Promising Biomarker Associated with Immunocytes Infiltration in Hyperoxia-Induced Bronchopulmonary Dysplasia.

Background: Bronchopulmonary dysplasia (BPD) refers to a chronic lung disease which is commonly observed in preterm infants. It can usually be caused by several pathological processes that endanger the long-term lung development, such as inflammation and immune dysfunction. Methods: In this study, a bioinformatics approach was applied to identify the differentially expressed immune-related genes (DEIRGs). We downloaded the transcriptional profiles (GSE32472 dataset) from the Gene Expression Omnibus (GEO) database and performed gene set enrichment analysis (GSEA). Cell type Identification By Estimating Relative Subsets of RNA Transcripts (CIBERSORT), microenvironment cell populations counter (MCPcounter), and Estimation of STromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) were used for the analysis of the immune cell infiltration landscape of BPD. A weighted co-expression network was subsequently constructed using weighted gene co-expression network analysis (WGCNA) to screen candidate differentially expressed immune related genes (DEIRGs). Results: GSEA results indicated that immune-related pathways were mainly involved in BPD. Ten significantly different immune cell types were observed between BPD and normal groups. A total of 228 DEGs in the turquoise module were identified, and 31 DEIRGs were further identified. Cluster of the differentiation 8 alpha (CD8A) expression was down-regulated in BPD, and its expression was validated by the GSE25286, GSE25293, GSE99633 datasets and qRT-PCR. In addition, CD8A expression was closely associated with immune cells infiltration, especially T cells CD8 and neutrophil. Conclusion: A distinct immune cell infiltration landscape was found between BPD and normal group. CD8A can be a novel candidate biomarker for BPD, which plays an essential role in the onset and progress of hyperoxia-related BPD via the disruption of immune cell functions.

MALAT1-mediated EZH2 Recruitment to the GFER Promoter Region Curbs Normal Hepatocyte Proliferation in Acute Liver Injury.

Background and Aims: The goal of this study was to investigate the mechanism by which the long noncoding RNA MALAT1 inhibited hepatocyte proliferation in acute liver injury (ALI). Methods: Lipopolysaccharide (LPS) was used to induce an ALI cellular model in HL7702 cells, in which lentivirus vectors containing MALAT1/EZH2/GFER overexpression or knockdown were introduced. A series of experiments were performed to determine their roles in liver injury, oxidative stress injury, and cell biological processes. The interaction of MALAT1 with EZH2 and enrichment of EZH2 and H3K27me3 in the GFER promoter region were identified. Rats were treated with MALAT1 knockdown or GFER overexpression before LPS induction to verify the results derived from the in vitro assay. Results: MALAT1 levels were elevated and GFER levels were reduced in ALI patients and the LPS-induced cell model. MALAT1 knockdown or GFER overexpression suppressed cell apoptosis and oxidative stress injury induced cell proliferation, and reduced ALI. Functionally, MALAT1 interacted directly with EZH2 and increased the enrichment of EZH2 and H3K27me3 in the GFER promoter region to reduce GFER expression. Moreover, MALAT1/EZH2/GFER was activated the AMPK/mTOR signaling pathway. Conclusion: Our study highlighted the inhibitory role of reduced MALAT1 in ALI through the modulation of EZH2-mediated GFER.

Neuroprotective Effect of Angiopoietin2 Is Associated with Angiogenesis in Mouse Brain Following Ischemic Stroke.

Angiogenic factors play an important role in protecting, repairing, and reconstructing vessels after ischemic stroke. In the brains of transient focal cerebral ischemic mice, we observed a reduction in infarct volume after the administration of Angiopoietin 2 (Angpt2), but whether this process is promoted by Angpt2-induced angiogenesis has not been fully elaborated. Therefore, this study explored the angiogenic activities, in reference to CD34 which is a marker of activated ECs and blood vessels, of cultured ECs in vitro and in ischemic damaged cerebral area in mice following Angpt2 administration. Our results demonstrate that Angpt2 administration (100 ng/mL) is neuroprotective by significantly increasing the CD34 expression in in vitro-cultured ECs, reducing the infarct volume and mitigating neuronal loss, as well as enhancing CD34+ vascular length and area. In conclusion, these results indicate that Angpt2 promotes repair and attenuates ischemic injury, and that the mechanism of this is closely associated with angiogenesis in the brain after stroke.

The effectiveness of physical therapy interventions in reducing falls among people with multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: Falls are common among People with Multiple Sclerosis (PwMS) and can result in significant consequences. Summary of the evidence of effectiveness of Physical Therapy (PT) to manage fall risks is needed. OBJECTIVE: To investigate the effectiveness of PT interventions to reduce fall related outcomes in PwMS. METHODS: Electronic databases of PubMed, PEDro, Web of Science, Scopus, SportDiscuss and CINAHL were searched. Randomized Controlled Trials (RCTs) and pre-post studies that examined the effectiveness of any PT interventions to target falls in PwMS were included. Two independent reviewers extracted the data. The Cochrane risk of bias assessment tool and the quality assessment tool for before-after studies were used for RCTs and pre-post studies, respectively. The Grading Recommendations, Assessment, Development and Evaluation- GRADE was used to rate the overall quality of evidence. RESULTS: Twenty articles with 819 participants were included in the review and 16 articles in meta-analysis. Only home-based exercise was found to significantly reduce the number of ambulatory fallers (risk ratio = 0.53, 95% CI 0.31 to 0.91, P = 0.02) with Multiple Sclerosis. Limited evidence exists on PT interventions to reduce falls among non-ambulatory PwMS. CONCLUSION: The overall very low to moderate quality of evidence presented showed the effectiveness of PT interventions to reduce fall outcomes in PwMS is limited. However, home-based exercise showed potential to reduce fall outcomes in ambulatory PwMS. There is a need to develop PT interventions to reduce fall outcomes in non-ambulatory PwMS due to a scarcity of evidence in this population. REGISTRATION: The protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO: CRD 42020150297).

The Effectiveness of Exercise Interventions to Improve Gait and Balance in Individuals with Lower Limb Amputations: A Systematic Review and Meta-analysis.

OBJECTIVE: To investigate the effectiveness of exercise interventions to improve gait and balance in individuals with lower limb amputations. METHODS: A systematic search was conducted on the PubMed, Scopus, Web of Science, SPORTDiscuss, and CINAHL databases until January 2022. Only randomized control trials that evaluated adults (>18 years old) with lower limb amputations and compared any exercise intervention with a traditional prosthetic training were included in the study. Two independent researchers screened articles for inclusion, extracted data, and evaluated the methodological quality of the trials. Findings were summarized and meta-analysis was conducted. RESULTS: Fifteen randomized clinical trials with 594 participants were included in the study and 12 in quantitative synthesis. Meta-analysis indicates that exercise interventions significantly improved walking distance measured with the 2-Minute Walking Test compared to traditional training (mean difference-MD: 8.38, 95% CI: 2.54-14.23; P < 0.01). Gait speed performance also significantly improved after exercise interventions compared to traditional training (MD: 0.10, 95% CI, 0.03-0.16, P <0.01). Meta-analysis of exercise interventions compared to traditional training on the Locomotor Capabilities Index, Timed Up and Go, and Activities-specific Balance Confidence did not show a statistically significant difference (P > 0.05). However, the qualitative analysis demonstrated significant improvement in balance performance after different exercise interventions and traditional training. The studies demonstrated overall good methodological quality. CONCLUSION: Specific exercise interventions are more effective than traditional prosthetic training to improve walking speed and walking distance among people with lower limb amputation. Findings on balance outcomes are inconsistent and deserve further exploration.

Effectiveness and safety of early combined utilization of budesonide and surfactant by airway for bronchopulmonary dysplasia prevention in premature infants with RDS: A meta-analysis.

OBJECTIVE: To address the effectiveness and safety of early airway combined utilization of budesonide and surfactant for bronchopulmonary dysplasia (BPD) prevention in premature infants with respiratory distress syndrome (RDS). METHODS: Literature retrieval was carried out in the PubMed, Web of Science, EMBASE, Cochrane Library, Wanfang, CQ VIP, and China National Knowledge Infrastructure databases, searching from the inception to September 2021. Stata 16.0 software was used for statistical analysis. RESULTS: This meta-analysis suggested that early combined utilization of budesonide and surfactant by airway have a superiority on BPD incidence (risk ratio [RR] = 0.62; 95% confidence interval [CI]: 0.54-0.71, p < 0.001], mortality (RR = 0.64; 95%CI: 0.45-0.92, p = 0.016), the composite outcome of BPD or mortality (RR = 0.58; 95%CI: 0.50-0.68, p < 0.001), the additional doses of surfactant (RR = 0.53; 95%CI: 0.44-0.63, p < 0.001), the duration of assisted ventilation (standard mean difference [SMD] = -1.14; 95%CI: -1.58 to -0.70, p < 0.001), duration of invasive ventilation(SMD = -1.77; 95% CI: -2.61 to -0.93, p < 0.001), and hospital stays (SMD = -1.11; 95% CI: -1.73 to -0.49, p = 0.001) in preterm infants with RDS. And these benefits were not associated with increased adverse outcomes. Furthermore, a decreased incidence of patent ducts arterious (PDA) (RR = 0.79; 95% CI: 0.65 to 0.97, p = 0.028) was found in premature infants treated with budesonide and surfactant. Subgroup analysis based on budesonide delivery methods (inhalation or intratracheal instillation) indicated that the decrease of mortality (RR = 0.63; 95% CI: 0.43-0.93, p = 0.019), duration of assisted ventilation (SMD = -0.95; 95% CI: -1.30 to -0.61, p < 0.001), hospital stays (SMD = -1.23; 95% CI: -2.05 to -0.41, p = 0.003) and PDA incidence (RR = 0.80; 95% CI: 0.65 to 0.99, p = 0.044) were mainly in budesonide intratracheal instillation subgroup, rather than in budesonide inhalation subgroup. CONCLUSIONS: This meta-analysis suggested that early combined utilization of budesonide and surfactant by airway might be an effective and safe clinical practice for BPD prevention in premature infants with RDS, especially when budesonide was delivered by intratracheal instillation. However, many of the included studies were small and were from Asian origin. More well-designed randomized controlled trials with larger sample sizes and longer follow-up from all over the world ought to be conducted in the future.

Effectiveness of Physical Therapy Interventions in Reducing Fear of Falling Among Individuals With Neurologic Diseases: A Systematic Review and Meta-analysis.

OBJECTIVE: To summarize the effectiveness of physical therapy interventions to reduce fear of falling (FOF) among individuals living with neurologic diseases. DATA SOURCES: PubMed, Physiotherapy Evidence Database, Scopus, Web of Science, PsycINFO, Cumulative Index to Nursing and Allied Health, and SportDiscuss were searched from inception until December 2019. STUDY SELECTION: Clinical trials with either the primary or secondary aim to reduce FOF among adults with neurologic diseases were selected. DATA EXTRACTION: Potential articles were screened for eligibility, and data were extracted by 2 independent researchers. Risk of bias was assessed by the Cochrane Risk of Bias tool for randomized controlled trials and the National Institutes of Health Quality Assessment Tool for pre-post studies. A meta-analysis was performed among trials presenting with similar clinical characteristics. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was used to rate the overall quality of evidence. RESULTS: Sixty-one trials with 3954 participants were included in the review and 53 trials with 3524 participants in the meta-analysis. The included studies presented, in general, with a low to high risk of bias. A combination of gait and balance training was significantly more effective compared with gait training alone in reducing FOF among individuals with Parkinson disease (PD) (mean difference [MD]=11.80; 95% CI, 8.22-15.38; P<.001). Home-based exercise and leisure exercise demonstrated significant improvement in reducing FOF over usual care in multiple sclerosis (MS) (MD=15.27; 95% CI, 6.15-24.38; P=.001). No statistically significant between-groups differences were reported among individuals with stroke and spinal cord injury. The overall quality of evidence presented in this review ranges from very low to moderate according to the assessment with the GRADE approach. CONCLUSIONS: Gait with lower limb training combined with balance training is effective in reducing FOF in individuals with PD. Also, home-based or leisure exercise is effective among individuals with MS. However, because of several limitations of the included studies, further research is needed to examine the effectiveness of FOF intervention among individuals with neurologic diseases.

A Newborn with Congenital Hyperinsulinism.

Objective: Our aim was to describe the molecular alterations in the ABCC8 gene in a child with congenital hyperinsulinism (CHI). Methods: Genetic analysis of the ABCC8 gene of a newborn infant with congenial hyperinsulinism was obtained. Results: There were two mutations in the ABCC8 gene, c.4412delT, and c.3979G > A, indicating a compound heterozygous mutation. The c.4412delT variant is associated with CHI, and the c.3979G > A variant is associated with neonatal diabetes. Treatment with diazoxide was not effective, octreotide treatment with acetate was effective. Conclusion: The combination of a mutation of the ABCC8 gene c.4412delT, associated with CHI, and the mutation of c.3979G > A, associated with neonatal diabetes, resulted in a neonate with hypoglycemia. The mechanism remains unclear.

[The relationship between TNF-alpha and the injury of renal tubular cells caused by anoxia/reoxygenation].

AIM: To investigate the relationship between TNF-alpha and renal tubular cell injury caused by anoxia/reoxygenation. METHODS: Human renal proximal tubular cell line HK-2 was used as model. Anoxia/reoxygenation were produced by covering/de-covering the cell culture with liquid paraffin wax. The level of TNF-alpha and the activity of lactate dehydrogenase(LDH) in the culture medium was determined by radioimmunoassay(RIA) and biochemical methods, respectively. Trypan blue exclusion was used to measure cell viability. RESULTS: Anoxia/reoxygenation could increase TNF-alpha level and LDH activity, but decrease viability of HK-2 cells. TNF-alpha level was positively correlated with LDH activity (r=0.89, P<0.05) and negatively with the cell viability (r=-0.91, P<0.05). CONCLUSION: TNF-alpha induced by anoxia/reoxygenation may participate in the process of renal tubular cell injury.

[Replication of a model of injury to human renal proximal tubular cells induced by hypoxia/reoxygenation].

OBJECTIVE: To replicate a new model of injury to human renal proximal tubular cells (HK-2) induced by hypoxia/reoxygenation. METHODS: Human renal proximal tubular cell line HK-2 cell was used as the target cell. Tubular cells were divided into six groups: 4 hours of hypoxia, 12 hours of hypoxia, 24 hours of hypoxia, and 24 hours of hypoxia followed by reoxygenation 4, 12 or 24 hours later groups. Each group was accompanied by a control group. Hypoxic culture conditions were produced by covering the culture with liquid paraffin. Trypan blue exclusion was used for cell count and cell viability. The activity of lactate dehydrogenase (LDH) in the culture medium was determined by biochemical method. RESULTS: After being challenged by hypoxia followed by reoxygenation, trypan blue exclusion rate was greater, cell count and cell viability were lower, and the activity of LDH was increased. It indicated that the destruction of integrity of cellular membrane was induced by ischemia/reperfusion injury, and the tubular cells may be injured irreversibly. CONCLUSION: A simple model of hypoxic injury of renal tubular cells is replicated by covering the culture cells with liquid paraffin.