Plasminogen decreases Aß42 and Tau deposition, and shows multi-beneficial effects on Alzheimer's disease in mice and humans.

Alzheimer's disease (AD) is the most common neurodegenerative disorder in the world. The aggregation of both amyloid beta (Aß) peptides extracellularly and Tau proteins intracellularly plays key roles in the pathological consequences of AD, which lead to cholinergic neurodegeneration and eventually death. Currently, there are no effective methods to stop the progression of AD. Using ex vivo, in vivo and clinical approaches, we investigated the functional effects of plasminogen on the widely used FAD, Aß42 oligomer or Tau intracranial injection-induced AD mouse model and explored its therapeutic effects on patients with AD. The results show that intravenously injected plasminogen rapidly crosses the blood‒brain barrier (BBB); increases plasmin activity in the brain; colocalizes with and effectively promotes the clearance of Aß42 peptide and Tau protein deposits ex vivo and in vivo; increases the choline acetyltransferase (ChAT) level and decreases the acetylcholinesterase (AChE) activity; and improves the memory functions. Clinically, when GMP-level plasminogen was administered to 6 AD patients for 1-2 weeks, their average scores on the Minimum Mental State Examination (MMSE), which is a standard scoring system used to measure the memory loss and cognitive deficits, were extremely significantly improved by 4.2 ± 2.23 points, e.g., an average increase from 15.5 ± 8.22 before treatment to 19.7 ± 7.09 after treatment. The preclinical study and pilot clinical study suggest that plasminogen is effective in treating AD and may be a promising drug candidate.

Flexible application of scar tissue flaps in scar contracture release surgery: A retrospective study.

BACKGROUND: Complete release of scar contracture often relies on surgery, but if the surgery injures normal skin tissue triggers new wounds and scarring, which adds insult to injury for the patient. OBJECTIVE: To explore a method that uses scar tissue to repair the defect after the release of scars and try to avoid damage to normal skin tissue. MATERIALS AND METHODS: Forty-eight scar contracture patients admitted to our hospital from October 2014 to October 2019 were treated with scar tissue flaps (including Subcutaneous pedicle rhomboid flap, Z-plasty flap, 5-flap, and their combination model) and minor defects in combination with little scattered skin grafts. Medical and demographic data were collected on each patient. Assessed the joint range of motion (ROM) preoperatively and postoperatively, and complication was recorded. The rate of scar contracture recurrence was recorded at a follow-up of 6-24 months. RESULTS: Twenty-eight cases of scar contracture located in the joint sites, 20 in the trunk. All the surgical outcomes were satisfied, with significant improvement in contracture scarring and joint status. Postoperative joint range of motion (ROM) showed a significant improvement in comparison with preoperative mobility, whereas the difference was statistically significant (p < 0.05). After 24 months of follow-up, five joints showed recontraction, with a recurrence rate of 10.42%. CONCLUSION: Scar contracture could be efficiently treated by properly designing incisions and making the most of the scar tissue flap, to minimize and avoid damage to the normal skin.

Sesquiterpene lactones from Xanthium sibiricum Patrin alleviate asthma by modulating the Th1/Th2 balance in a murine model.

BACKGROUND: Asthma is a complex airway disease involving a variety of cells and cytokines. Xanthium sibiricum Patrin ex Widder (X. sibiricum) is a traditional Chinese medicine for various immune diseases, especially allergic rhinitis and asthma. Sesquiterpene lactones are the main bioactive and most abundant constituent, and are characteristic component of the plant. We explore whether sesquiterpene lactones from X. sibiricum (SL-XS) is the main active constitute for its anti-asthma activity. PURPOSE: In the present study, SL-XS was isolated, the major compounds were isolated and identified in extract of SL-XS, and the anti-asthma activity of SL-XS was validated in vivo. METHODS: SL-XS was isolated by a standard phytochemical method. The structures of major sesquiterpene lactones were identified by NMR and LC-MS spectra. The contents of major SL-XS were analyzed by HPLC. The anti-asthma effect of SL-XS was evaluated in a house dust mite (HDM)-induced mouse model. RESULTS: The sesquiterpene lactones were isolated from X. sibiricum, and five major constituents i.e., 8­epi-xanthatin-1ß, 5ß-epoxide (1), tomentosin (2), 8­epi-xanthatin (3), 2­epi-xanthumin (4) and sibiriolide B (5) were identified from SL-XS. Oral administration of SL-XS dose-dependently ameliorated airway inflammation and remodeling in HDM-challenged asthma mouse model. Furthermore, SL-XS treatment inhibited the upregulation of proinflammatory and Th2 cytokines, while reversed the downregulation of Th1 related cytokines. In addition, SL-XS regulated the balance between T-bet and GATA-3. Moreover, SL-XS inhibited the upregulation of JAK1, p-JAK1, JAK2, p-JAK2, JAK3, p-JAK3 and p-STAT6 in HDM-challenged mice. CONCLUSION: The sesquiterpene lactones including five major constituents may be the main anti-asthma active constituent of X. sibiricum. SL-XS exerted its anti-asthma effect by modulating the Th1/Th2 balance via the JAK/STAT signaling pathway.

Circular RNA HECTD1 knockdown inhibits transforming growth factor-beta/ small mothers against decapentaplegic (TGF-ß/Smad) signaling to reduce hypertrophic scar fibrosis.

Scars are nearly impossible to avoid after a skin injury, but despite advancements in the treatment modalities, they remain a clinical problem, especially hypertrophic scars (HS). Many studies include the mechanism of formation and inhibition of HS, but it is not fully understood yet. Circular RNA HECTD1 (circHECTD1), for the first time, has been found to have roles in HS physiology. We determined the relative circHECTD1 levels in HS fibrous cells and tissues by RT-qPCR. Afterward, the effect of circHECTD1 knockdown on the proliferation, migration, invasion, fibrosis, and Transforming Growth Factor-beta/small mothers against decapentaplegic (TGF-ß/Smad) signaling was studied using CCK-8, wound healing, Transwell, and western blot assays. After the role of circHECTD1 was clarified, its targeted micro RNA (miR) was predicted using the Starbase database, and we constructed a miR-142-3p mimic to study the details of its regulation mechanism. We used the TargetScan database to predict the downstream target high mobility group box 1 (HMGB1) of miR-142-3p, and the luciferase report assay verified the binding, and then its effect was determined by RT-qPCR. circHECTD1 is highly expressed in HS tissues and human skin hypertrophic scar fibroblasts (HSF); its loss of function inhibits cell proliferation, migration, invasion, fibrosis, and TGF-ß/Smad signaling. However, miR-142-3p inhibitor reverses the effect of circHECTD1 on all the above-mentioned aspects, including HMGB1 expression. In conclusion, circHECTD1 knockdown interrupts TGF-ß/Smad signaling through miR-142-3p/HMGB1 and suppresses scar fibrosis.

Effects of multiple modes of UltraPulse fractional CO2 laser treatment on extensive scarring: a retrospective study.

The main therapeutic options for extensive scarring (e.g., > 20% of the total body surface area, or TBSA) after burns and trauma have focused on conservative treatments, such as compression, moisturization, and topical agent application. However, these treatments may not achieve optimal effects due to the large size and complexity of the scars. UltraPulse fractional CO2 laser treatment is a novel approach that is currently a subject of intense interest; this treatment is most widely used to improve texture, pliability, and pigmentation in all types of scars. However, no studies on the independent use of UltraPulse fractional CO2 laser treatment for extensive scars have been reported. This retrospective study evaluated a total of 21 patients, whose scars covered 20 to 65% TBSA. Scar thickness was measured by ultrasonography before treatment. Personalized treatment modalities and parameters were set according to the scar type and thickness. Scar formation and treatment effects were evaluated by photography, the Patient and Observer Scar Assessment Scale (POSAS), and patients' judgment of effectiveness. Where the scars covered joints, joint function was assessed by measuring the maximum range of motion (ROM). With laser therapy, scars became flatter and lighter; furthermore, pruritus, pain, and discomfort decreased significantly. POSAS scores significantly decreased after laser therapy, including the item scores for pain and pruritus. There were no instances of joint contracture, ROM reduction, apparent functional impairment, serious adverse events, or comorbidities. This study demonstrates the safety and efficiency of UltraPulse fractional CO2 laser treatment for extensive scarring.

Diagnostic Key Points and Surgical Management of Necrotizing Fasciitis: A Retrospective Study.

Necrotizing fasciitis (NF) is a fatal disease with a high mortality rate that can be easily misdiagnosed. The aim of this study was to improve the diagnostic rate of NF and overall survival. We conducted a single-center, retrospective, noncontrolled study involving 36 patients who were admitted to our department between December 2017 and October 2019, and summarized the diagnostic key points and timing of surgical treatment. All patients were diagnosed at our department and underwent multiple courses of treatment. The records included information regarding underlying diseases, bacterial culture results, laboratory risk indicator for necrotizing fasciitis (LRINEC) score, number of procedures, and type of antibiotics. All 36 cases of NF were cured and showed good patient condition on follow-up; the mean number of surgeries was three, and the mean duration of hospitalization was 37 days (range, 21-83 days). The LRINEC scores of 16 patients were ≥8 points. Seventeen patients with underlying diabetic disease had higher inflammatory index scores than those without diabetes. The LRINEC scores of patients with (n = 17) and without (n = 19) DM were 7.40 ± 2.99 and 3.80 ± 2.39, respectively (P < .01). Cases of NF that were treated with early incision and surgical abscess drainage required fewer surgeries and a shorter length of hospitalization. Thus, surgeons should be more aware of NF and aim to make an early and accurate diagnosis using various approaches. Complete surgical debridement plays an essential role in NF treatment, and diabetes mellitus is a significant adverse factor that exacerbates the severity of NF. Negative-pressure techniques are useful in cases involving nonanaerobic infections and cause minimal complications.

Reconstruction of Major Burns With Stevens-Johnson Syndrome: A Case Report and Literature Review.

Stevens-Johnson syndrome (SJS) is a severe type of pleomorphic erythema and a rare disorder of the skin and mucous membranes, which can lead to serious infections, pulmonary embolism, acute respiratory distress syndrome, multiple organ dysfunction syndrome, and other serious consequences. Patients with SJS are usually treated in burn centers. SJS complicated by severe burns is very rare, and this is associated with a high risk of infection and other more serious complications. With SJS, the availability of donor sites is compromised given the lack of healthy epidermis, and this makes it more difficult to treat. The patient was a 52-year-old man with 45% TBSA burns with 40% TBSA full-thickness burns on both lower limbs. During treatment, his condition was complicated by SJS, renal failure, and respiratory failure. After 31 days, he was transferred to our department. On the 22nd day, the patient recovered from SJS, and after undergoing four skin grafting procedures, the burn wounds healed, and the donor site had healed spontaneously. He was discharged after 86 days of treatment in our department. In conclusion, major burns complicated with SJS are rare clinical presentations. The skin affected by the drug eruptions can be used as a donor site for transplantation to the burn wounds, and this donor area can also heal.

A novel alginate localization molding technique for cross-sectional area measurement of human tendon to access biomechanical properties.

Accurate determination of the biomedical properties of connective tissue such as tendons and ligaments is dependent on the accurate measurement of their cross-sectional area (CSA). To date, techniques for determining cross-sectional areas of ligaments and tendons have been less than ideal due to their complex geometries and their deformations under external load. A novel non-destructive technique has been developed for determining the cross-sectional area of tendon by locating the tendon rupture, in which aqueous rapid curing alginate dental molding materials, digital photography and computerized image analysis are utilized. This technique marks tendons and alginate molds at 1 cm interval and then tendons are taken out for tensile test. Real-time video is recorded to locate the position of tendon rupture. The corresponding alginate slice is found and then analysis through computer image processing software to obtain a more accurate CSA at tendon rupture, which can be used to calculate the stress and young's modulus of tendon. The accuracy of this technique has been investigated and comparisons have been made with the alginate un-localization molding technique and ellipse estimation technique. Results show this technique can provide accurate CSA values (within 2%) and great reproducibility (coefficient of variation = 0.8%). The technique is non-destructive, can obtain morphological information of soft tissue and can detect cavities.

Cross-Sectional Area Measurement Techniques of Soft Tissue: A Literature Review.

Evaluation of the biomechanical properties of soft tissues by measuring the stress-strain relationships has been the focus of numerous investigations. The accuracy of stress depends, in part, upon the determination of the cross-sectional area (CSA). However, the complex geometry and pliability of soft tissues, especially ligaments and tendons, make it difficult to obtain accurate CSA, and the development of CSA measurement methods of soft tissues continues. Early attempts to determine the CSA of soft tissues include gravimetric method, geometric approximation technique, area micrometer method, and microtomy technique. Since 1990, a series of new methods have emerged, including medical imaging techniques (e.g. magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound imaging (USI)), laser techniques (e.g. the laser micrometer method, the linear laser scanner (LLS) technique, and the laser reflection system (LRS) method), molding techniques, and three-dimensional (3D) scanning techniques.

Myelodysplastic Syndrome with Complex Chromosomal Abnormalities: A Case Report and Literature Review.

OBJECTIVE: Karyotype is the most important diagnostic and prognostic parameter in myelodys-plastic syndrome (MDS). Here, we describe a novel case of MDS with complex chromosomal abnormalities. CASE PRESENTATION: A 55-year-old Chinese female was admitted to the hospital for facial edema and a loss of appetite. Bone marrow aspiration showed the blast cell count 3.6%. Erythrocyte hyperplasia was active, megaloblastoid change was observed, and a wide variability of nuclear numbers, as well as variability of size and shape was present. Bone marrow chromosomal analyses showed 45~48, X, -X, -4, t (5;8) (q13;q22), add (7) (q11), add (13) (p11), -14, del (16) (p13), add (19) (q13), -20, i(21)(q10),+4~6mar [cp15]/46,XX[5]. The patient was diagnosed with MDS with WPSS of the high risk group. IPSS was medium risk-2. IPSS-R was categorized as the extremely high risk group. CONCLUSION: The prognosis and treatment of MDS with complex chromosomal abnormalities are still uncertain, and further studies are needed.

Emission of sulfur dioxide from polyurethane foam and respiratory health effects.

Recently, health damage to children exposed to synthetic polyurethane (PU) running tracks has aroused social panic in China. Some possible toxic volatiles may be responsible for these damages. However, the exact cause remains unclear. We have detected a low concentration of sulfur dioxide (SO2; 1.80-3.30 mg/m3) on the surface of the PU running track. Surprisingly, we found that SO2 was generated from the PU running track, and even such a low concentration of SO2 could induce severe lung inflammation with hemorrhage, inflammatory cell infiltration, and inflammatory factor secretion in mice after 2-week exposure. Prolonged exposure (5 weeks) to the SO2 caused chronic pulmonary inflammation and pulmonary fibrosis in the mice. Peripheral hemogram results showed that platelet concentration increased significantly in the SO2 group compared to that in the control group, and the proportion of blood neutrophils and monocytes among total leukocytes was more imbalanced in the SO2 group (16.6%) than in the control group (8.0%). Further histopathology results of sternal marrow demonstrated that hematopoietic hyperplasia was severely suppressed with increased reticular stroma and adipocytes under SO2 exposure. These data indicate that a low concentration of SO2 generated spontaneously from PU running track outdoors as a secondary product is still harmful to health, as it impairs the respiratory system, hematopoiesis, and immunologic function. This indicates that the low-concentration SO2 could be a major cause of diseases induced by air pollution, such as chronic obstructive pulmonary disease.

[Effect of Regulating PPARγ by mTOR Signaling on Adipogenesis of Bone Marrow Mesenchymal Stem Cells from Aplastic Anemia].

OBJECTIVE: To study the effect and mechanism of mTOR signaling on adipogenesis of bone marrow mesenchymal stem cells(BM-MSCs) from aplastic anemia (AA) patients through regulation of PPARγ. METHODS: BM-MSCs were isolated from 24 newly diagnosed AA patients and 24 healthy controls. The surface antigen expression of BM-MSCs was identified by flow cytometry. The capacity of adipogenic differentiation of BM-MSCs was determined by lipid droplets based on Oil Red O staining and by the expression of FABP4 based on Western blot. Protein levels of mTOR signaling and PPARγ were tested by immunofluorescence and Western blot. RESULTS: AA BM-MSCs displayed an enhanced capacity of differentiating into adipocytes, compared with control BM-MSCs. It was found that mTOR was activated in AA BM-MSCs. Moreover, the expression levels of p-mTOR and PPAR-γ in AA BM-MSCs showed a parallel differentiation-dependent increase during adipogenic differentiation, which were significantly higher than that of control BM-MSCs at the same time point of adipogenic differentiation. mTOR inhibitor rapamycin did not only inhibit the adipogenic differentiation of BM-MSCs from AA pateints at the early-middle stage, but also partly reversed the adipogenic differention of BM-MSCs from AA pateints at the late stage by PPARγ regulation. CONCLUSION: mTOR signaling may play a critical role in the adipogenic differentiation of BM-MSCs from AA patients by positively regulating PPARγ expression.

[Advances in research of the mechanism of "covert disorder" in diabetic skin].

The diabetic ulceration is not uncommon, and becomes refractory, as the skin in a diabetic patient is relatively thin as well as hypoesthetic and less sensitive to temperature. As there are already preexisting histological and cellular derangement in the skin, healing of the skin injury is difficult, thus resulting in an intractable ulceration. When diabetes is not controlled, the skin contents of sugar and advanced glycation end product accumulate, invoking cellular deformation and accumulation of matrix metalloproteinases (MMP), resulting in an imbalance between MMP and its inhibitors, malfunction of growth factors, and inflammatory reaction. These processes lead to obvious skin thinning, denaturation of connective tissues, thickening of vascular basal membrane, and neuropathy, etc. These pathological alterations could be recognized as "covert disorder" of skin in diabetic patients and may be underlying disorders in producing indolent diabetic ulcers.