Lesion Area Research Articles

Mechanism of Liangfang Wenjing Decoction in treatment of hypoxia on endometriosis with cold coagulation and blood stasis by regulating CHCHD4 expression

To explore the mechanism of Liangfang Wenjing Decoction regulating coiled-coil-helix coiled-coil-helix domain containing 4(CHCHD4) in the treatment of hypoxia on endometriosis(EMs) with cold coagulation and blood stasis. The rat model of cold coagulation and blood stasis syndrome was prepared by the ice-water bath method, and then the EMs model was established by autologous intimal transplantation. The rats were randomly divided into model group, low, medium, and high(4.7, 9.4, and 18.8 g·kg~(-1)) dose groups of Liangfang Wenjing Decoction, Shaofu Zhuyu Decoction group, and sham group, with 10 rats in each group. The rats were given intragastric administration for four weeks. During the modeling, the general condition and vaginal smear of rats were observed, and the blood flow of ears and uterus were detected by laser speckle contrast imaging(LSCI) to judge the syndrome of cold coagulation and blood stasis. After the administration, the general condition of the rats was observed, and the area of ectopic lesions was measured by caliper. The localization and expression of CHCHD4 and hypoxia inducible factors-1α(HIF-1α) were detected by immunohistochemistry, and the mRNA and protein expressions of CHCHD4 and HIF-1α were detected by real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot. The primary culture of ectopic endometrial stromal cells(ESCs) from EMs patients was performed, and the CHCHD4 overexpression plasmid was constructed and transfected to establish the ESCs model of CHCHD4 overexpression. The cells were divided into the control group, CHCHD4 overexpression group, CHCHD4 overexpression+control serum group, and CHCHD4 overexpression+Liangfang Wenjing Decoction serum group. The protein expression of CHCHD4 and HIF-1α was detected by Western blot, and the glucose consumption and lactic acid level were detected. The cell proliferation was detected by MTT assay. The experiment found that compared with normal rats, the modeling rats showed symptoms of cold coagulation and blood stasis, such as mental malaise, reduced diet and drinking water, disordered estrous cycle, and blocked blood circulation in ears and uterine microvessels. Compared with the sham group, the ectopic lesions in the model group were uplifted, and the mRNA and protein expressions of CHCHD4 and HIF-1α were significantly increased(P<0.05). Compared with the model group, the symptoms of cold coagulation and blood stasis in each treatment group were improved, and the area of ectopic lesions was significantly reduced(P<0.05 or P<0.01). The mRNA and protein expression levels of CHCHD4 and HIF-1α were significantly decreased(P<0.05 or P<0.01). In the cell model, compared with the control group, the expression of CHCHD4, HIF-1α protein, glucose consumption, lactic acid level, and cell proliferation activity in the CHCHD4 overexpression group were significantly increased(P<0.01). Compared with the CHCHD4 overexpression group, there was no significant change in each index in the control serum group, while the protein expression of CHCHD4 and HIF-1α in the Liangfang Wenjing Decoction serum group was decreased significantly(P<0.05 or P<0.01). The glucose consumption, lactic acid level, and cell proliferation activity decreased significantly(P<0.01). It can be seen from the above that the therapeutic effect of Liangfang Wenjing Decoction on EMs with cold coagulation and blood stasis might be related to reducing the expression of CHCHD4 and then improving the hypoxia of ectopic lesions and ectopic ESCs.

Fingertip amputations in children: Atasoy flap’s indications and limitations

IntroductionThe Atasoy flap is considered simple and reliable for covering distal digital defects in adults. Various studies in children have shown more contrasting results, particularly in terms of aesthetics and function. The aim of this study is to evaluate the long-term results of this flap specifically in children, in order to determine its limitations and indications. HypothesisThe Atasoy flap is reliable and reproducible for coverage of distal digital substance loss up to zone 2 in children. Materials and methodsFifty-six children who benefited from an Atasoy flap operated on between January 2017 and January 2020 were included. Lesion area, operative technique, postoperative complications (infection, healing difficulties, necrosis), and ultimately nail appearance, cold intolerance or finger pain, finger eviction, extension defect, and final parental satisfaction were analyzed. ResultsForty-nine children were evaluated with a mean follow-up of 18 months (min = 3 months, max = 38 months, SD = 11.3 months). Eighteen children had a hook nail, resulting in 6 of them having their finger excluded. The majority of hook nails were found in zone III and in proximal zone II lesions (12 cases). Eighty-nine percent of children with distal suture fixation to the nail bed (8 children) had this complication. Cold intolerance was present in 9 children. There were no cases of extension failure or early post-operative complications. Final parent satisfaction was 9.1/10 (min = 5, max = 10, SD = 1.3). ConclusionThe Atasoy flap in children appears reliable for covering loss of distal digital substance. The main complication is the occurrence of hook nails. Compliance with its indications (transverse substance loss not exceeding the proximal third of zone II) and a precise surgical technique (distal needle fixation without suturing to the nail bed, deep flap lift, non-closure of the donor site) help limit this risk. Level of evidenceIV; retrospective study.

Validation of the Cut-Plane Method for Accurate Measurement of Side-Branch Ostium Area in Coronary Bifurcation Lesions: A 3D-OCT Analysis.

This study aimed to validate the effectiveness, accuracy, and feasibility of the cut-plane method for measuring the side branch (SB) ostium area in three-dimensional optical coherence tomography (3D-OCT) pullbacks performed in the main branch (MB). A total of 109 sets of OCT pullbacks from the MB and SB of coronary artery bifurcation lesions were analyzed using Vivolight OCT software. Measurements of the SB ostium area from the MB and SB pullbacks were analyzed. Measurements of the SB ostium area from the actual SB pullback were used as a reference. 3D cut-plane analysis was used to estimate the correlations and mean errors with the reference measurements. Thirty-four sets of OCT images from the C7XR system and 75 sets from the CornarisTM system were analyzed using Vivolight software. There was a strong correlation between the reference measurements of the SB ostium area and the measurements obtained through 3D cut-plane analysis in the overall dataset (r = 0.925). This correlation was observed consistently with both the C7XR system (r = 0.955) and CornarisTM system (r = 0.900). Similar results were found in subset analyses of true and nontrue bifurcations (r = 0.936; r = 0.898, respectively) and in left main (LM) or non-LM bifurcation subsets (r = 0.932; r = 0.873, respectively). There were strong correlations between measurements of the SB ostium area by 3D-OCT and the reference measurements, and thus may be a reliable and accurate alternative to direct OCT pullback examinations of the SB.

Qingxiong Ointment and its Active Ingredient, Shikonin Treat Psoriasis through HIF-1 Signaling Pathway.

Psoriasis is a common chronic inflammatory skin disorder. Qingxiong ointment (QX) is a natural medicinal combination frequently employed in clinical treatment of psoriasis. However, the active ingredients of QX and its precise mechanisms of improving psoriasis remain unclear. This study elucidated the effects of QX on an Imiquimod (IMQ)-induced mouse model of psoriasis while also exploring the regulation of the active ingredient of QX, shikonin, on the HIF-1 signaling pathway in HaCaT cells. A mouse model of psoriasis was established through topical application of IMQ, and the local therapeutic effect of QX was evaluated using dorsal skin tissue with mouse psoriatic lesion and Psoriasis Area Severity Index (PASI) scores, hematoxylin-eosin (HE) staining, and immunohistochemical staining. Elisa and qPCR were employed to identify changes in the expression of inflammation-related factors in the mouse dorsal skin. Immunofluorescence was used to assess changes in the expression of T cell subsets before and after treatment with various doses of QX. HPLC was used to analyze the content of shikonin, and network pharmacology was employed to analyze the main targets of shikonin. Immunofluorescence was used to identify the effects of shikonin on the HIF-1 signaling pathway in IL6-induced psoriasis HaCaT cells. Finally, qPCR was used to identify the differential expression of the HIF-1 signaling pathway in skin tissues. QX significantly reduces PASI scores on the backs of IMQ-induced psoriasis mice. HE staining reveals alleviated epidermal thickness in the QX group. Immunohistochemical analysis shows a significant reduction in ICAM, KI67, and IL17 expression levels in the QX group. Immunofluorescence results indicate that QX can notably decrease the proportions of CD4+ T cells, γδ T cells, and CD8+ T cells while increasing the proportion of Treg cells. Network pharmacology analysis demonstrates that the main targets of shikonin are concentrated in the HIF-1 signaling pathway. Molecular docking results show favorable binding affinity between shikonin and key genes of the HIF-1 signaling pathway. Immunofluorescence results reveal that shikonin significantly reduces p-STAT3, SLC2A1, HIF1α, and NOS2 expression levels. qPCR results show significant downregulation of the HIF-1 signaling pathway at cellular and tissue levels. Our study revealed that QX can significantly reduce the dorsal inflammatory response in the IMQ-induced psoriasis mouse model. Furthermore, we discovered that its main component, shikonin, exerts its therapeutic effect by diminishing the HIF-1 signaling pathway in HaCaT cells.

Skin Homeostasis is Impaired in Hidradenitis Suppurativa Lesions: A Comparative Study

IntroductionHidradenitis suppurativa (HS) is a chronic skin disease whose impact on skin homeostasis has not been adequately studied at present. Knowledge about how skin function changes in these patients, and could be of interest not only to improve the topical management of the disease, but also as an objective measure of disease activity. The aim of this study was to compare skin homeostasis and the epidermal barrier function in lesional and healthy skin areas of patients with HS. MethodsWe conducted a cross-sectional study. Skin homeostasis and the epidermal barrier function of lesions were assessed in HS patients using validated tools. A healthy perilesional skin control was assigned to each lesion to compare skin homeostasis parameters. ResultsA total of 43 patients were included: 22 nodules, 10 abscesses and 25 draining tunnels were measured. The male-to-female ratio was 20:23, and the mean age, 35.95 years (SD, 14.82). Increased transepidermal water loss (TEWL) and erythema were found in nodules, abscesses and draining tunnel vs healthy skin. A direct association was observed between inflammatory nodules TEWL and IHS4 stage. In draining tunnels, a direct association was observed between TEWL and smoking. A trend of increasing TEWL values was observed as a function of Hurley stage. ConclusionHS lesions exhibit epidermal barrier dysfunction that depends on the severity of inflammatory activity. These results could be useful to develop objective classification systems for the severity and degree of involvement of HS or help in the development of vehicles for specific drugs, antiseptics and dressings for the management of this disease.

Poster 267: Relationship Between Sagittal Tibial Tubercle-Trochlear Groove Distance and Outcomes Following Cartilage Restoration for Patellofemoral Articular Cartilage Lesions

Objectives: Increased contact force in the patellofemoral (PF) joint is a known contributor to cartilage damage and pain. A tibial tubercle that is posterior to the trochlear groove may lead to aberrant loading and cartilage wear. The sagittal tibial-tubercle trochlear groove distance (sTT-TG), defined as the distance between the nadir of the trochlear groove and the most anterior aspect of the tibial tubercle, aids in quantifying the degree of risk of acquiring new lesions. However, the relationship between sTT-TG and patient-reported outcomes following surgery has not been assessed. Therefore, the purpose of this study is to assess the association between sTT-TG and post-operative outcomes in patients undergoing cartilage restoration procedures for PF articular cartilage lesions. Methods: A retrospective review of patients who underwent osteochondral allograft (OCA) transplantation or autologous chondrocyte implantation (ACI) at a single academic institution from 2010 to 2020 was conducted. Patients were included they underwent OCA or ACI for a high-grade (Outerbridge 3 or 4) articular cartilage lesion located in the patellofemoral joint (unipolar or bipolar), if they were between 18 and 50 years of age at the time of surgery, had magnetic resonance imaging (MRI) available, and had a minimum 2-year clinical follow-up. Demographic data such as age, sex, body mass index (BMI), as well as defect characteristics including size, number, and grade were collected. Before surgery, sTT-TG distance was measured independently on axial T2-weighted MRI sequences by two raters (Rater A and Rater B). Both raters measured the sTT-TG for the entire cohort at two different time points with a two-week time interval between each rater’s initial and follow-up measurements. The Interclass Coefficient (ICC) using a single measure, absolute agreement, two-way mixed effects model was used to test the intra-rater reliability of Rater A and Rater B; mean measures were used to assess the inter-rater reliability for the combined mean of the two rater’s measurements. Patients were surveyed to assess pain and satisfaction on a Visual Analog Scale (VAS) from 0 to 100. Functional outcomes were collected using the Knee Injury and Osteoarthritis Outcome Score (KOOS). The rate of return to sports, complications, and graft failure were also recorded [JT1]. An independent samples t-test was used to compare lesion size between the OCA and ACI group. Linear and logistic regression models accounting for age, sex, BMI, and sTT-TG distance were used to assess the relationship between sTT-TG and PROs. Results: A total of 76 patients, mostly female (61.8%), with a mean age of 31.9 ± 8.3 years, BMI of 26.8, and 60.6 ± 23.6-month follow-up were included. There were 37 (48.7%) patients that underwent OCA transplantation and 39 (51.3%) that underwent ACI. A total of 98 lesions were identified, with the majority (n = 93, 94.9%) being Grade 4. Overall, 54 patients had unipolar lesions and 22 had bipolar lesions. The mean defect size was 2.9 ± 1.4 cm2 and 3.5 ± 2.9 cm2 for the OCA and ACI groups (p = 0.459), respectively, with an overall mean lesion area of 3.2 ± 2.3 cm2. Intra-rater reliability for sTT-TG measurements at each time point was excellent for Rater A (ICC of 0.99 [0.986-0.994] p<0.001) and Rater B (ICC of 0.99 [0.985-0.994]). Inter-rater reliability was excellent (ICC of 0.97 [0.955-.982] p<0.001), with an overall mean sTT-TG of -4.98 ± 4.93 mm (range: -18.9, 5.7). On average, 48.7% (n = 37) of patients returned to sport and of those, 22.4% (n=17) returned to a similar or higher level of sport activity. Mean pain and satisfaction were 26.7 ± 25.1 and 73.8 ± 27.7, respectively. Collectively, the mean KOOS subscores were - KOOS symptoms: 71.4 ± 2.3, KOOS pain: 79.5 ± 2.0, KOOS sport: 60.2 ± 2.8, and KOOS QoL: 52.0 ± 2.6. When controlling for age, sex, BMI, and follow-up, sTT-TG was not predictive of RTS (p=0.706), pain (p=0.698), satisfaction (0.757), or any KOOS subscore (p>0.05). Although, older age was associated with worse satisfaction (-0.819, 95% CI [-1.608,-0.03] and inferior KOOS pain (-0.606, 95% CI [-1.096,-0.116]), KOOS sport (-0.739, 95% CI [-1.445,-0.032]), and KOOS QoL (-0.786, 95% CI [-1.455,-0.117] p<0.05). Conclusions: In this cohort of patients that underwent an OCA or ACI for PF cartilage lesions, sTT-TG was not predictive of post-operative patient reported functional outcomes or complications. These findings suggest that while a more posterior tibial tubercle (negative sTT-TG) may contribute to a higher incidence of cartilage pathology, patients can have favorable short-term outcomes following cartilage restoration with OCA or ACI.

Inhibition of hepatic bile salt uptake by Bulevirtide reduces atherosclerosis in Oatp1a1−/−Ldlr−/− mice

Bile salts can strongly influence energy metabolism through systemic signaling, which can be enhanced by inhibiting the hepatic bile salt transporter Na+ taurocholate cotransporting polypeptide (NTCP), thereby delaying hepatic reuptake of bile salts to increase systemic bile salt levels. Bulevirtide is an NTCP inhibitor and was originally developed to prevent NTCP-mediated entry of Hepatitis B and D into hepatocytes. We previously demonstrated that NTCP inhibition lowers body weight, induces glucagon-like peptide-1 (GLP1) secretion, and lowers plasma cholesterol levels in murine obesity models. In humans, a genetic loss-of-function variant of NTCP has been associated with reduced plasma cholesterol levels. Here, we aimed to assess if Bulevirtide treatment attenuates atherosclerosis development by treating female Ldlr−/− mice with Bulevirtide or vehicle for 11 weeks. Since this did not result in the expected increase in plasma bile salt levels, we generated Oatp1a1−/−Ldlr−/− mice, an atherosclerosis-prone model with human-like hepatic bile salt uptake characteristics. These mice showed delayed plasma clearance of bile salts and elevated bile salt levels upon Bulevirtide treatment. At the study endpoint, Bulevirtide-treated female Oatp1a1−/−Ldlr−/− mice had reduced atherosclerotic lesion area in the aortic root that coincided with lowered plasma LDL-c levels, independent of intestinal cholesterol absorption. In conclusion, Bulevirtide, which is considered safe and is EMA-approved for the treatment of Hepatitis D, reduces atherosclerotic lesion area by reducing plasma LDL-c levels. We anticipate that its application may extend to atherosclerotic cardiovascular diseases, which warrants clinical trials.

Therapeutic application of nicotinamide: As a potential target for inhibiting fibrotic scar formation following spinal cord injury.

We aimed to confirm the inhibitory effect of nicotinamide on fibrotic scar formation following spinal cord injury in mice using functional metabolomics. We proposed a novel functional metabolomics strategy to establish correlations between gene expression changes and metabolic phenotypes using integrated multi-omics analysis. Through the integration of quantitative metabolites analysis and assessments of differential gene expression, we identified nicotinamide as a functional metabolite capable of inhibiting fibrotic scar formation and confirmed the effect invivo using a mouse model of spinal cord injury. Furthermore, to mimic fibrosis models invitro, primary mouse embryonic fibroblasts and spinal cord fibroblasts were stimulated by TGFβ, and the influence of nicotinamide on TGFβ-induced fibrosis-associated genes and its underlying mechanism were examined. Administration of nicotinamide led to a reduction in fibrotic lesion area and promoted functional rehabilitation following spinal cord injury. Nicotinamide effectively downregulated the expression of fibrosis genes, including Col1α1, Vimentin, Col4α1, Col1α2, Fn1, and Acta2, by repressing the TGFβ/SMADs pathway. Our functional metabolomics strategy identified nicotinamide as a metabolite with the potential to inhibit fibrotic scar formation following SCI by suppressing the TGFβ/SMADs signaling. This finding provides new therapeutic strategies and new ideas for clinical treatment.

Poster 266: Sagittal Tibial Tubercle-Trochlear Groove Distance Predicts Patellofemoral Chondral Lesion Size and Is Associated With Postoperative Complications

Objectives: The purpose of this study was to assess the association between sagittal tibial tubercle-trochlear groove (sTT-TG) distance and patellofemoral chondral lesion size in patients undergoing cartilage restoration procedures. Methods: A retrospective review of patients who underwent an osteochondral allograft (OCA) transplantation or autologous chondrocyte implantation (ACI) was conducted. Patients were included if they had an articular cartilage lesion located in the patella, trochlea, or both (bipolar lesions). Lesion size of individual patella and trochlear lesions were measured intra-operatively at implantation. Total lesion area was calculated as a sum of all present chondral lesions in the patellofemoral joint. The preoperative sTT-TG distance was measured independently on magnetic resonance imaging (MRI) by 2 authors and an Interclass Correlation Coefficient (ICC) was calculated. Categorical and linear regression models accounting for demographic variables and sTT-TG distance were used to assess the relationship between sTT-TG and lesion size. Results: Eighty patients (85 knees) composed of 50 women (mean age: 31.5±10.4 years) were included. Forty-one patients underwent OCA transplantation and 44 underwent ACI. Intra-rater (ICC: 0.99, 0.98) and inter-rater reliability (ICC: 0.96) were excellent for sTT-TG measurements. A bivariate correlation analysis demonstrated that sTT-TG was significantly inversely related to MRI defect size (-0.45, p<0.01). Similarly, sTT-TG was inversely related to patellar lesion size and total lesion area, but not trochlear lesion size (Table 1). When controlling for demographics, a more negative sTT-TG remained an independent predictor of larger defects on MRI and patellar lesions: 9.3 mm2 and 9.8 mm2 lesion size increase on MRI (p<0.001) and intraoperatively (p=0.01), respectively, for every 1 mm decrease in sTT-TG. For every 1 mm increase in sTT-TG, the risk of all complications occurring decreased by 14.1% (ß=0.859, p=0.007). Conclusions: In this cohort of patients undergoing patellofemoral cartilage restoration, a more negative sTT-TG distance is a predictor of larger patellar lesions and increased risk for all complications.

Paper 38: Comparison of Clinical Outcomes and Return to Sport Rates Between Osteochondral Allograft Transplantation and Autologous Chondrocyte Implantation for Articular Cartilage Lesions in the Patellofemoral Joint

Objectives: The purpose of this study is to compare clinical outcomes and return to sport (RTS) rates between patients that undergo osteochondral allograft (OCA) transplantation and autologous chondrocyte implantation (ACI), or matrix-induced autologous chondrocyte implantation (MACI), for patellofemoral articular cartilage defects. Methods: A retrospective review of patients who underwent an OCA, ACI, and MACI from 2010 to 2020 with a minimum two-year follow-up was conducted. Patient-reported outcomes (PROs) collected included: Visual Analog Scale for pain and satisfaction, Knee Injury and Osteoarthritis Outcome Score (KOOS), and return to sport (RTS) status. Logistic regression controlling for age, sex, BMI, bone marrow edema, mechanism of injury, lesions size and location was used to identify predictors of worse outcomes. Results: A total of 95 patients with a mean age of 32.1 years (± 10.0) and mean BMI of 26.5 (± 5.9) were included. ACI or MACI was performed in 55 cases (57.9%) and OCA in 40 (42.1%). Satisfaction was not significantly different between groups. VAS pain scores were higher in the OCA group, but did not reach significance. Overall, KOOS pain was significantly poorer in the OCA group than the ACI/MACI group, while KOOS symptoms, KOOS sport, and KOOS QOL subscores were non-significantly different. Overall, RTS rate was 54.3.%, with no significant difference in return between OCA or ACI/MACI groups. Increasing age was associated with lower satisfaction in the OCA group and poorer outcomes in the ACI/MACI group, while larger lesion area was associated with lower satisfaction and poorer outcomes scores in the ACI/MACI group. Conclusions: Clinical outcomes and return to sport rates are similar in patients that undergo OCA or ACI/MACI for patellofemoral articular cartilage defects, except in measures of pain, where patients undergoing OCA may experience more symptoms, particularly in the setting of trochlear defects.

CMM: A CNN-MLP Model for COVID-19 Lesion Segmentation and Severity Grading.

In this paper, a CNN-MLP model (CMM) is proposed for COVID-19 lesion segmentation and severity grading in CT images. The CMM starts by lung segmentation using UNet, and then segmenting the lesion from the lung region using a multi-scale deep supervised UNet (MDS-UNet), finally implementing the severity grading by a multi-layer preceptor (MLP). In MDS-UNet, shape prior information is fused with the input CT image to reduce the searching space of the potential segmentation outputs. The multi-scale input compensates for the loss of edge contour information in convolution operations. In order to enhance the learning of multiscale features, the multi-scale deep supervision extracts supervision signals from different upsampling points on the network. In addition, it is empirical that the lesion which has a whiter and denser appearance tends to be more severe in the COVID-19 CT image. So, the weighted mean gray-scale value (WMG) is proposed to depict this appearance, and together with the lung and lesion area to serve as input features for the severity grading in MLP. To improve the precision of lesion segmentation, a label refinement method based on the Frangi vessel filter is also proposed. Comparative experiments on COVID-19 public datasets show that our proposed CMM achieves high accuracy on COVID-19 lesion segmentation and severity grading.

Adaptive enzyme-responsive self-assembling multivalent apelin ligands for targeted myocardial infarction therapy

Microvascular dysfunction following myocardial infarction exacerbates coronary flow obstruction and impairs the preservation of ventricular function. The apelinergic system, known for its pleiotropic effects on improving vascular function and repairing ischemic myocardium, has emerged as a promising therapeutic target for myocardial infarction. Despite its potential, the natural apelin peptide has an extremely short circulating half-life. Current apelin analogs have limited receptor binding efficacy and poor targeting, which restricts their clinical applications. In this study, we utilized an enzyme-responsive peptide self-assembly technique to develop an enzyme-responsive small molecule peptide that adapts to the expression levels of matrix metalloproteinases in myocardial infarction lesions. This peptide is engineered to respond to the high concentration of matrix metalloproteinases in the lesion area, allowing for precise and abundant presentation of the apelin motif. The changes in hydrophobicity allow the apelin motif to self-assemble into a supramolecular multivalent peptide ligand-SAMP. This self-assembly behavior not only prolongs the residence time of apelin in the myocardial infarction lesion but also enhances the receptor-ligand interaction through increased receptor binding affinity due to multivalency. Studies have demonstrated that SAMP significantly promotes angiogenesis after ischemia, reduces cardiomyocyte apoptosis, and improves cardiac function. This novel therapeutic strategy offers a new approach to restoring coronary microvascular function and improving damaged myocardium after myocardial infarction.

Aggregate-aware model with bidirectional edge generation for medical image segmentation

Accurate segmentation of lesion areas plays an important role in medical imaging-assisted diagnosis and treatment. Accurate boundary information can help doctors develop precise surgical plans and improve patient prognosis. However, automatic segmentation methods often struggle to accurately segment edges due to the random shape, size, and location of regions of interest (ROI). This problem is compounded in medical images, where the difference in pixel intensity between foreground and background is significantly smaller than in natural images. In this study, we propose an aggregate-aware model with bidirectional edge generation (Ambeg) for medical image segmentation. To overcome the problem of blurred edges between foreground and background in medical images, we design a deep learning model via a multi-task learning strategy and obtain richer visual features to guide segmentation. Furthermore, an Edge Feature Fusion (EFF) module is developed to combine spatial correlation information of lesion edges between adjacent images for more accurate edge segmentation. Finally, we design a new evaluation metric, the Boundary DSC segmentation consistency measure, to evaluate the edge segmentation accuracy of medical image segmentation methods. We utilize dilation and erosion operations in morphological methods to construct lesion edge labels. In addition, we use expansion and erosion rates to regulate the dimensions of the edge region to assess the requirements of different diseases for edge segmentation accuracy. The proposed approach is particularly noteworthy for achieving state-of-the-art results on medical image segmentation datasets, including BraTS 2022 (MRI), BraTS 2020 (MRI) and COVID-19–20 (CT), which have different modalities of datasets. It has an impressive Hausdorff distance of 4.62 mm and a sensitivity score of 92.45 % on BraTS 2020. Compared with existing assessment methods such as Dice score, Boundary DSC segmentation consistency measure focuses on the hard-to-segment lesion edge region rather than the easy-to-segment lesion center region, which provides a more comprehensive reference for physicians to choose automatic segmentation methods. In addition, since the boundary shapes of medical images are complex and diverse, we utilize morphological methods to obtain the boundary labels to ensure the smoothness of the boundary. Moreover, the approach is easy to implement and has a low computational cost, making it an attractive option for practical medical imaging applications.

A spectrofluorimetric method of testing a transplanted pedicle skin flap in eyelid neoplasm surgery

Purpose: to develop a method for assessing metabolic changes in pedicle skin flaps using spectrofluorimetry in eyelid neoplasm surgery. Material and methods. 14 patients (mean age 74.50 ± 7.14 years) were operated for eyelid neoplasms with tissue defects replaced by pedicle flaps. The area of eyelid lesion achieved 90 %. In 100 % of cases, a histological examination revealed basal cell carcinoma. Metabolic changes of the skin in the transplanted flap and in the symmetrical area of the fellow eye were assessed using the spectrofluorimetric method 3 days and 3 months after the surgery. A number of successive spectra of fluorimetric parameters were taken from each site, whereupon the mean values of the Metabolic Shift Index were calculated. Results. Differences in the spectrofluorimetric parameters of the metabolic shift between the area with the transplanted flap and the symmetrical area were revealed on the third day after surgery (p = 0.00058) and 3 months after it (p = 0.0317). The obtained results indicate a partial preservation of the hypoxic state of the skin on the third postoperative day and the complete restoration of trophism 3 months after the surgery (p = 0.043), as well as the onset of scarring of the transplanted flap by the latter time point. Conclusion. A technique for assessing metabolic changes in eyelid skin has been developed, which enabled the establishment of normal spectrofluorimetric values in this area and helped reveal the changes in the indices of metabolic shift in the transplanted pedicle flaps in the early postoperative periods and throughout the entire follow-up period. 3 months after the surgical treatment, the indices of metabolic changes in the transplanted pedicle flap come close to normal values.

Pemphigus oral lesions area index (POLAI): A new scoring scale for assessing oral pemphigus vulgaris

AbstractObjectivesCurrent scales for Pemphigus vulgaris (PV) do not adequately represent the clinical variability of oral lesions. This study aimed to develop an independent scale, the Pemphigus Oral Lesions Area Index (POLAI), for assessment of oral PV exclusively, and compare POLAI, Pemphigus Disease Area Index (PDAI), Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and Oral Disease Severity Score (ODSS) regarding inter‐ and intra‐observer reliability and validity.Materials and MethodsRetrospective cohort included 209 sets of digital‐photographs. Additional clinical cohort included 32 PV patients. All visits were assessed by four clinicians using the PDAI, ABSIS, ODSS and POLAI, and were rated by three specialists using the Physician's Global Assessment (PGA).ResultsThe intraclass correlation coefficient showed the inter‐observer reliability with 0.89 and 0.86 for PDAI, 0.87 for ABSIS, 0.93 for ODSS, 0.96 for POLAI, and 0.97 and 0.96 for PGA. Intra‐observer agreements showed excellent reliability for all 4 scores. Highest correlation was observed between PGA and POLAI (correlation coefficients were 0.96). The mean time taken to complete each scale was within 1.5 min.ConclusionPOLAI is valid for the assessment of oral PV with superior inter‐ and intra‐observer reliability to PDAI, ABSIS and ODSS, and is feasible in clinic.

Topical application of simvastatin acid sodium salt and atorvastatin calcium salt in vitiligo patients. Results of the randomized, double-blind EVRAAS pilot study

Contemporary treatment of vitiligo remains a great challenge to practitioners. The vast majority of currently conducted clinical trials of modern therapeutic methods are focused on systemic medications, while there is only a very limited number of reports on new topical treatment in vitiligo. With their pleiotropic activities statins turned out to be efficient in the treatment of various autoimmune/autoinflammatory disorders. The randomized, double-blind placebo-controlled study of topical administration of the active forms of simvastatin and atorvastatin has been designed to evaluate their efficacy in patients with vitiligo. The study was registered in clinicaltrials.gov (registration number NCT03247400, date of registration: 11th August 2017). A total of 24 patients with the active form of non-segmental vitiligo were enrolled in the study. The change of absolute area of skin lesions, body surface area and vitiligo area scoring index were evaluated throughout the 12 week application of ointments containing simvastatin and atorvastatin. Measurements were performed with planimetry and processed using digital software. Use of active forms of simvastatin and atorvastatin did not result in a significant repigmentation of the skin lesions throughout the study period. Within the limbs treated with topical simvastatin, inhibition of disease progression was significantly more frequent than in the case of placebo (p = 0.004), while the difference was not statistically significant for atorvastatin (p = 0.082). Further studies of topical simvastatin in vitiligo patients should be considered.

Mingjing granule inhibits the subretinal fibrovascular membrane of two-stage laser-induced neovascular age-related macular degeneration in rats.

The study aims to investigate the protective effect of Mingjing granule (MG) in a fibrovascular membrane rat model of neovascular age-related macular degeneration (nAMD) and explore the underlying mechanism. The nAMD fibrovascular membrane model was established by two-stage laser photocoagulation. BN rats were randomly divided into four groups: the model group was gavaged with distilled water, the anti-VEGF group was given an intravitreous injection of ranibizumab, the MG + anti-VEGF group was gavaged with MG combined with an intravitreous injection of ranibizumab, and the normal group not modeled only fed conventionally. Lesions were evaluated by color fundus photograph, optical coherence tomography, fundus fluorescein angiography, and retinal pigment epithelial-choroid-sclera flat mount. The changes in the retinal structure were observed by histopathology. The expression of inflammatory cell markers F4/80, Iba-1, and glial fibrillary acidic protein (GFAP); the fibrosis-related factors collagen-1, fibronectin, α-smooth muscle actin (α-SMA), and transforming growth factor-beta (TGF-β); and the complement system-related factors C3a and C3aR in the retina were detected by immunofluorescence or qRT-PCR. The current study revealed that MG + anti-VEGF administration more significantly reduced the thickness of fibrovascular lesions, suppressed vascular leakage (exudation area and mean density value), inhibited the area of fibrovascular lesions, and restrained the formation of the fibrovascular membrane than the anti-VEGF agent alone in the two-stage laser-induced rat model. The fluorescence intensities of F4/80, Iba-1, collagen-1, fibronectin, TGF-β, and C3aR showed more significant inhibition in MG + anti-VEGF-treated rats than the anti-VEGF agent alone. The mRNA expression levels of F4/80, Iba-1, GFAP, collagen-1, fibronectin, α-SMA, TGF-β, and C3a showed lower levels in rats treated with MG + anti-VEGF than the anti-VEGF agent alone. Combining MG with anti-VEGF treatment inhibits the growth of the fibrovascular membrane more effectively than using anti-VEGF treatment alone. The mechanism underlying this effect may involve limiting inflammatory cell aggregation, controlling complement system activation, and decreasing the expression of the fibrotic protein.

Exploratory multi-omics analysis reveals host-microbe interactions associated with disease severity in psoriatic skin

Psoriasis (Pso) is a chronic inflammatory skin disease that poses both physical and psychological challenges. Dysbiosis of the skin microbiome has been implicated in Pso, yet a comprehensive multi-omics analysis of host-microbe interactions is still lacking. To bridge this gap, we conducted an exploratory study by adopting the integrated approach that combines whole metagenomic shotgun sequencing with skin transcriptomics. This was a cross-sectional study, adult patients with plaque-type Psoriasis (Pso) and healthy volunteers were included. Skin microbiota samples and biopsies were collected from both lesional and non-lesional skin areas on the lower back. Weighted Gene Correlation Network Analysis (WGCNA) was employed for co-expression network analysis, and cell deconvolution was conducted to estimate cell fractions. Taxonomic and functional features of the microbiome were identified using whole metagenomic shotgun sequencing. Association between host genes and microbes was analyzed using Spearman correlation. Host anti-viral responses and interferon-related networks were identified and correlated with the severity of psoriasis. The skin microbiome showed a greater prevalence of Corynebacterium simulans in the PASI severe-moderate groups, which correlated with interferon-induced host genes. Two distinct psoriatic clusters with varying disease severities were identified. Variations in the expression of cell apoptosis-associated antimicrobial peptides (AMPs) and microbial aerobic respiration I pathway may partly account for these differences in disease severity. Our multi-omics analysis revealed for the first time anti-viral responses and the presence of C.simulans associated with psoriasis severity. It also identified two psoriatic subtypes with distinct AMP and metabolic pathway expression. Our study provides new insights into understanding the host-microbe interaction in psoriasis and lays the groundwork for developing subtype-specific strategies for managing this chronic skin disease. The research has received funding from the FP7 (MAARS-Grant 261366) and the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 821511 (BIOMAP). The JU receives support from the European Union's Horizon 2020 research and innovation programme and EFPIA. This publication reflects only the author's view and the JU is not responsible for any use that may be made of the information it contains. GAM was supported by a scholarship provided by CAPES-PRINT, financed by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES (Brazilian Government Agency). The authors thank all patients who participated in our study.

UCP2-ACGAN: An adaptive condition GAN guided by U-shaped context perceptual processor for PET/CT images fusion

In order to better highlight the lesion area information and edge detailed information of the fused images, an adaptive condition Generative Adversarial Network (GAN) guided by U-shaped context perceptual processor (UCP2-ACGAN) for Positron Emission Tomography (PET) and Computed Tomography (CT) images fusion is proposed in this paper. Firstly, the network architecture of single generator and dual relative discriminators with weights sharing is used in UCP2-ACGAN. Secondly, a multi-granularity adaptive feature extraction module from coarse to fine (MGAFE) is proposed in generator, it is used to extract the valid information contained in the source images. Thirdly, a dual branch feature interactive fusion module guided by U-shaped context perceptual processor (UCP2-DBFIF) is proposed in generator. The context perceptual feature maps are obtained by U-shaped context perceptual processor (UCP2) and multiply them with the feature extraction results as the guiding conditions in the fusion process. In addition, in order to supplement the effective information lost during the feature fusion process, this paper converges the feature information of different granularity during the feature extraction stage. Finally, compared to the best of the 6 comparison methods, the results of comparison experiments show that UCP2-ACGAN is effective on several evaluation metrics values. For example, on the evaluation metrics of Average Gradient (AG), Edge Intensity (EI), Spatial Frequency (SF), Visual Information Fidelity (VIF) and Mutual Information (MI), the metrics values of CT mediastinal window images and PET fused images average increased by 30.74%, 29.35%, 40.24%, 35.47% and 26.18%.

Therapeutic effect and mechanism of piracetam for the treatment of spinal cord injury in rats through MAPK pathway

To explore mechanism of piracetam for the treatment of spinal cord injury in rats through mitogen-activated protein kinase (MAPK) pathway. Fifty-four healthy 6-week-old SD female rats with body weight of 80 to 100 g were divided into sham operation group, spinal cord injury group and piracetam group by random number table method, with 18 rats in each group. Spinal cord injury model was established in spinal cord injury group and piracetam group using percussion apparatus, while sham operation group did not damage spinal cord. Piracetam group was injected with piracetam injection through tail vein according to 5 ml·kg-1 standard, once a day for 3 days;the other two groups were injected with normal saline at the same dose, the same frequency and the same duration. The rats were sacrificed at 1, 3, and 7 days after surgery, and changes of Basso, Beattie and Bresnahan (BBB) locomotor rating scale was observed and compared. Enzyme-linked immunosorbent assay (ELISA) was used to detect spinal cord inflammatory factors, such as interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-1β (interleukin-1β), necrosis factor-α (IL-1β) and tumor necrosis factor-α (TNF-α);HE staining was used to observe morphological changes of rats with spinal cord injury, and immunohistochemistry was used to observe expression level of aquaporin 4 (AQP4). The activation of MAPK signaling pathway in spinal cord of rats after spinal cord injury was observed by western blotting (WB). BBB scores of sham operation group on 1, 3 and 7 day were 21 points. In spinal cord injury group, the scores were (1±1), (4±1) and (7±2);piracetam group was (1±1), (5±1), (9±2), respectively;the difference between spinal cord injury group and sham operation group was statistically significant (P<0.05). HE staining showed that no abnormality was found in sham operation group. In spinal cord injury group, bleeding and degeneration of spinal cord tissue appeared at 1 day after operation; flaky necrotic areas were appeared in spinal cord at 3 days after surgery, and spinal cord tissue began to slowly repair at 7 days after surgery. In piracetam group, the bleeding area was less than that of spinal cord injury group at 1 day after surgery;at 3 days after operation, the necrotic area was reduced and the range of nuclear disappearance was reduced; and the spinal cord began to recover slowly at 7 days after surgery. AQP4 staining of spinal cord of rats in sham operation group was weak at 1, 3 and 7 days after modeling, AQP4 staining was deepened and area increased in spinal cord injury group, AQP4 staining of piracetam group was lighter than that of spinal cord injury group, and the positive cells were slightly increased and the staining was slightly darker than that of sham operation group. At 1, 3 and 7 days, the level of IL-6, IL-10, IL-1β and TNF-α in spinal cord injury group were higher than those in sham operation group and piracetam group(P<0.05). Compared with spinal cord injury group, the area of spinal cord bleeding and necrosis were decreased by HE staining in piracetam group, and AQP4 staining was decreased by immunohistochemistry. WB results showed that P-ERK, P-JNK and P-P38 levels in spinal cord injury group at 3 days were higher than those in sham operation group and piracetam group(P<0.05). Piracetam not only showed significant effect in promoting motor function recovery after spinal cord injury, but also showed positive therapeutic potential in reducing lesion area, regulating AQP4 expression to reduce edema, and reducing inflammatory response by regulating MAPK signaling pathway.