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Background and objective: The circular RNA hsa_circ_0007755 is markedly upregulated in hypertrophic scars (HS), yet its functional roles in this fibroproliferative disorder remain to be elucidated. This investigation aims to delineate the regulatory mechanisms of hsa_circ_0007755 in HS and to decode its downstream molecular signaling pathways. Methods: We established a murine model of HS. Tissue histopathology was assessed using Hematoxylin and Eosin and Masson's trichrome staining. Peripheral blood from the animals was collected and the ratio of T-helper 1 (Th1) to T-helper 2 (Th2) cells was quantified via flow cytometry. The proliferation and apoptosis rates of human hypertrophic scar fibroblasts (hHSFs) were evaluated using the Cell Counting Kit-8 assay and flow cytometry, respectively. The invasive capacity of hHSFs was assessed via a Transwell assay. Co-culture experiments of hHSFs with T cells were conducted, and alterations in Th1/Th2 ratios were monitored using flow cytometry. Levels of cytokines, fibrosis-associated proteins, nuclear factor-kappaB (NF-κB) pathway-related protein, and C-X-C Motif Chemokine Ligand 2 (CXCL2) were quantified using Enzyme-Linked Immunosorbent Assay or Western blot analysis. The interactions between hsa_circ_0007755, miR-27b-3p, and CXCL2 were investigated using dual-luciferase reporter assays and RNA immunoprecipitation. Results: Both hsa_circ_0007755 and CXCL2 were highly expressed in HS, whereas miR-27b-3p was downregulated. Knockdown of hsa_circ_0007755 inhibited the proliferation and invasion of hHSFs, promoted apoptosis, and reduced the expression of fibrotic proteins α-SMA and Collagen I, as well as the phosphorylation of the inflammatory pathway protein p65. Co-culture experiments confirmed that hHSFs lowly expressing hsa_circ_0007755 showed a decreased Th1 cell proportion and an increased Th2 cell proportion, alongside lower levels of TNF-α and INF-γ and higher levels of IL-4 and IL-10. The effects of either knocking down or overexpressing hsa_circ_0007755 were reversed by knocking down either miR-27b-3p or CXCL2, respectively. hsa_circ_0007755 acted as a ''molecular sponge'' for miR-27b-3p, sequestering and diminishing its availability, thereby alleviating its suppression of the target gene CXCL2. Conclusion: hsa_circ_0007755 plays a pivotal role in modulating the immune response of HS by influencing the miR-27b-3p/CXCL2 axis, regulating the function and proportion of Th1 and Th2 cells, and thereby affecting the inflammatory and fibrotic processes in scar tissue.

Abstract Background Due to increasing life expectancy, almost half of people with type 2 diabetes are aged 65 years or over worldwide. When metformin alone does not control blood sugar, the choice of which second-line therapy to prescribe next is not clear from currently available evidence. The existence of frailty and comorbidities in older adults further increases the complexity of medical decision-making. As only a relatively small proportion of trials report results separately for older adults, the relative efficacy and safety of second-line therapies in older adults with type 2 diabetes mellitus are unknown and require further investigation. This individual participant data (IPD) network meta-analysis evaluates the relative efficacy and safety of second-line therapies on their own or in combination in older adults with type 2 diabetes mellitus. Methods All relevant published and unpublished trials will be identified. Studies published prior to 2015 will be identified from two previous comprehensive aggregate data network meta-analyses. Searches will be conducted in CENTRAL, MEDLINE, and EMBASE from 1st January 2015 onwards, and in clinicaltrials.gov from inception. Randomised controlled trials with at least 100 estimated older adults (≥ 65 years) receiving at least 24 weeks of intervention that assess the effects of glucose-lowering drugs on mortality, glycemia, vascular and other comorbidities outcomes, and quality of life will be eligible. The screening and data extraction process will be conducted independently by two researchers. The quality of studies will be assessed using the Cochrane risk of bias tool 2. Anonymised IPD of all eligible trials will be requested via clinical trial portals or by contacting the principal investigators or sponsors. Received data will be reanalysed where necessary to standardise outcome metrics. Network meta-analyses will be performed to determine the relative effectiveness of therapies. Discussion With the increasing number of older adults with type 2 diabetes worldwide, an IPD network meta-analysis using data from all eligible trials will provide new insights into the optimal choices of second-line antidiabetic drugs to improve patient management and reduce unnecessary adverse events and the subsequent risk of comorbidities in older adults. Systematic review registration PROSPERO CRD42021272686.

Abstract Background There is a high prevalence of autoimmune conditions in women specially in the reproductive years; thus, the association with adverse pregnancy outcomes has been widely studied. However, few autoimmune conditions/adverse outcomes have been studied more than others, and this umbrella review aims to consolidate existing knowledge in this area with the aim to provide new knowledge and also identify gaps in this research area. Methods Medline, Embase, and Cochrane databases were searched from inception to December 2023. Screening, data extraction, and quality appraisal (AMSTAR 2) were done by two independent reviewers. Data were synthesised narratively and quantitatively. Relative risks (RR)/odds ratio (OR) with 95% confidence intervals were reported. Results Thirty-two reviews were included consisting of 709 primary studies. The review reported the association between 12 autoimmune conditions and 16 adverse pregnancy outcomes. Higher risk of miscarriage is reported in women with Sjögren’s syndrome RR 8.85 (95% CI 3.10–25.26) and systemic lupus erythematosus (SLE) OR 4.90 (3.10–7.69). Pre-eclampsia was reported higher in women with type 1 diabetes mellitus (T1DM) OR 4.19 (3.08–5.71) and SLE OR 3.20 (2.54–4.20). Women reported higher risk of diabetes during pregnancy with inflammatory bowel disease (IBD) OR 2.96 (1.47–5.98). There was an increased risk of intrauterine growth restriction in women with systemic sclerosis OR 3.20 (2.21–4.53) and coeliac disease OR 1.71 (1.36–2.14). Preterm birth was associated with T1DM OR 4.36 (3.72–5.12) and SLE OR 2.79 (2.07–3.77). Low birth weight babies were reported in women with women with SLE or systemic sclerosis OR 5.95 (4.54–7.80) and OR 3.80 (2.16–6.56), respectively. There was a higher risk of stillbirth in women with T1DM OR 3.97 (3.44–4.58), IBD OR 1.57 (1.03–2.38), and coeliac disease OR 1.57 (1.17–2.10). T1DM in women was associated with 32% lower odds of small for gestational age baby OR 0.68 (0.56–0.83). Conclusions Pregnant women with autoimmune conditions are at a greater risk of developing adverse pregnancy outcomes. Further research is required to develop better preconception to postnatal care for women with autoimmune conditions.

Abstract To investigate the distortion process of thin-walled box girders, three commonly used methods based on energy variational calculus and static balance analysis are optimized. A generalized analytical formula for box-girder distortion research is derived, and a fourth-order distortion control differential equation is obtained. Typical numerical examples are used to verify and compare the three methods. The results show that the value of distortional warping normal stress calculated by the optimized methods is slightly different from the literature values and that the maximum error between methods does not exceed 5.39%. The calculation results of Method 2 and Method 3 are similar. The values of the geometric distortion characteristics calculated by the three methods are related to the cross-sectional form of the box girder and the distortion analysis process, and the calculated values are not unique. The absolute value of the peak normal stress of distortion on the top plate of a thin-walled box girder with a cantilever plate is smaller than that on the bottom plate. Under a concentrated distortion load, the distribution of the distortion deformation along the length of a simply supported box girder with only end diaphragm is not consistent, and there is reverse deformation near the beam end.

BackgroundDiabetic retinopathy (DR) is the most frequent complication of type 2 diabetes and remains the leading cause of preventable blindness. Current clinical decisions regarding the administration of antidiabetic drugs do not sufficiently incorporate the risk of DR due to the inconclusive evidence from preceding meta-analyses. This umbrella review aimed to systematically evaluate the effects of antidiabetic drugs on DR in people with type 2 diabetes.MethodsA systematic literature search was undertaken in Medline, Embase, and the Cochrane Library (from inception till 17th May 2022) without language restrictions to identify systematic reviews and meta-analyses of randomized controlled trials or longitudinal studies that examined the association between antidiabetic drugs and DR in people with type 2 diabetes. Two authors independently extracted data and assessed the quality of included studies using the AMSTAR-2 (A MeaSurement Tool to Assess Systematic Reviews) checklist, and evidence assessment was performed using the GRADE (Grading of recommendations, Assessment, Development and Evaluation). Random-effects models were applied to calculate relative risk (RR) or odds ratios (OR) with 95% confidence intervals (CI). This study was registered with PROSPERO (CRD42022332052).ResultsWith trial evidence from 11 systematic reviews and meta-analyses, we found that the use of glucagon-like peptide-1 receptor agonists (GLP-1 RA), sodium-glucose cotransporter-2 inhibitors (SGLT-2i), or dipeptidyl peptidase-4 inhibitors (DPP-4i) was not statistically associated with the risk of DR, compared to either placebo (RR: GLP-1 RA, 0.98, 0.89-1.08; SGLT-2i, 1.00, 95% CI 0.79-1.27; DPP-4i, 1.17, 0.99-1.39) or other antidiabetic drugs. Compared to other antidiabetic drugs, meglitinides (0.34, 0.01-8.25), SGLT-2i (0.73, 0.10-5.16), thiazolidinediones (0.92, 0.67-1.26), metformin (1.15, 0.81-1.63), sulphonylureas (1.24, 0.93-1.65), and acarbose (4.21, 0.44-40.43) were not statistically associated with the risk of DR. With evidence from longitudinal studies only, insulin was found to have a higher risk of DR than other antidiabetic drugs (OR: 2.47, 95% CI: 2.04-2.99).ConclusionOur results indicate that antidiabetic drugs are generally safe to prescribe regarding the risk of DR among people with type 2 diabetes. Further robust and large-scale trials investigating the effects of insulin, meglitinides, and acarbose on DR are warranted.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=332052, identifier CRD42022332052.

Epilepsy is a chronic brain disease with recurrent seizures. Mesial temporal lobe epilepsy (MTLE) is the most common pathological cause of epilepsy. With the development of computer-aided diagnosis technology, there are many auxiliary diagnostic approaches based on deep learning algorithms. However, the causes of epilepsy are complex, and distinguishing different types of epilepsy accurately is challenging with a single mode of examination. In this study, our aim is to assess the combination of multi-modal epilepsy medical information from structural MRI, PET image, typical clinical symptoms and personal demographic and cognitive data (PDC) by adopting a multi-channel 3D deep convolutional neural network and pre-training PET images. The results show better diagnosis accuracy than using one single type of medical data alone. These findings reveal the potential of a deep neural network in multi-modal medical data fusion.

Objectives The use of medications among pregnant women has been rising over the past few decades but the reporting of polypharmacy has been sporadic. The objective of this review is to identify literature reporting the prevalence of polypharmacy among pregnant women, the prevalence of multimorbidity in women taking multiple medications in pregnancy and associated effects on maternal and offspring outcomes.Design MEDLINE and Embase were searched from their inception to 14 September 2021 for interventional trials, observational studies and systematic reviews reporting on the prevalence of polypharmacy or the use of multiple medications in pregnancy were included.Data on prevalence of polypharmacy, prevalence of multimorbidity, combinations of medications and pregnancy and offspring outcomes were extracted. A descriptive analysis was performed.Results Fourteen studies met the review criteria. The prevalence of women being prescribed two or more medications during pregnancy ranged from 4.9% (4.3%–5.5%) to 62.4% (61.3%–63.5%), with a median of 22.5%. For the first trimester, prevalence ranged from 4.9% (4.7%–5.14%) to 33.7% (32.2%–35.1%). No study reported on the prevalence of multimorbidity, or associated pregnancy outcomes in women exposed to polypharmacy.Conclusion There is a significant burden of polypharmacy among pregnant women. There is a need for evidence on the combinations of medications prescribed in pregnancy, how this specifically affects women with multiple long-term conditions and the associated benefits and harms.Tweetable abstract Our systematic review shows significant burden of polypharmacy in pregnancy but outcomes for women and offspring are unknown.PROSPERO registration number CRD42021223966.

AimWe aimed to compare the mortality of individuals at low, moderate, and high risk of diabetic foot disease (DFD) in the context of newly diagnosed type 2 diabetes, before developing active diabetic foot problem.MethodsThis was a population-based cohort study of adults with newly diagnosed type 2 diabetes utilizing IQVIA Medical Research Data. The outcome was all-cause mortality among individuals with low, moderate, and high risk of DFD, and also in those with no record of foot assessment and those who declined foot examination.ResultsOf 225,787 individuals with newly diagnosed type 2 diabetes, 34,061 (15.1%) died during the study period from January 1, 2000 to December 31, 2019. Moderate risk and high risk of DFD were associated with increased mortality risk compared to low risk of DFD (adjusted hazard ratio [aHR] 1.50, 95% CI 1.42, 1.58; aHR 2.01, 95% CI 1.84, 2.20, respectively). Individuals who declined foot examination or who had no record also had increased mortality risk of 75% and 25% vs. those at low risk of DFD, respectively (aHR 1.75, 95% CI 1.51, 2.04; aHR 1.25, 95% CI 1.20, 1.30).ConclusionIndividuals with new-onset type 2 diabetes who had moderate to high risk of DFD were more likely to die compared to those at low risk of DFD. The associations between declined foot examination and absence of foot examinations, and increased risk of mortality further highlight the importance of assessing foot risk as it identifies not only patients at risk of diabetic foot ulceration but also mortality.

Particle breakage continuously changes the grading of granular materials and has a significant effect on their mechanical behaviors. Revealing the evolution pattern of particle breakage is valuable for development and validation of constitutive models for crushable materials. A series of parallel triaxial compression tests along the same loading paths but stopped at different axial strains were conducted on two coral sands with different particle sizes under drained and undrained conditions. The tested specimens were carefully sieved to investigate the intermediate accumulation of particle breakage during the loading process. The test results showed that under both drained and undrained conditions, particle breakage increases continuously with increasing axial strain but exhibits different accumulating patterns, and higher confining pressures lead to greater particle breakage. Based on the test results, the correlations between particle breakage and the stress state as well as the input energy were examined. The results demonstrated that either the stress state or input energy alone is inadequate for describing the intermediate process of particle breakage evolution. Then, based on experimental observation, a path-dependent model was proposed for particle breakage evolution, which was formulated in an incremental form and reasonably considers the effects of the past breakage history and current stress state on the breakage rate. The path-dependent model successfully reproduced the development of particle breakage during undrained triaxial compression using the parameters calibrated from the drained tests, preliminarily demonstrating its effectiveness for different stress paths.

In this study, the effect of ionizing radiation on 8-hydroxy-2′-deoxyguanosine (8-OHdG) in human peripheral blood was investigated. Blood samples were collected from 230 radiation workers and 8 patients who underwent radiotherapy for population study. Blood samples from 2 healthy individuals were irradiated with different X-ray doses for in vitro experiment, and levels of 8-OHdG in serum and cell culture supernatants were assessed by enzyme-linked immunosorbent assay. Observations demonstrated the positive relationships between serum 8-OHdG level and radiation dose and working period were observed, and serum 8-OHdG levels were higher among interventional radiation workers than among other hospital radiation workers. In addition, 8-OHdG yields in supernatants increased, peaked at 3 Gy of radiation dose, and then decreased with further increases in radiation; the dose–response curve obtained fitted a polynomial function. By contrast, a similar trend was not found in radiotherapy patients. The present study suggests that 8-OHdG may be a useful biomarker reflecting oxidative damage among workers occupationally exposed to low-dose radiation.