Large Relative Surface Area of Hematomas Predict a Poor Outcome in Patients with Spontaneous Intracerebral Hemorrhage.

OBJECTIVE: The aim of this study is to investigate the predictive value of relative surface area of hematoma on poor prognosis of spontaneous intracerebral hemorrhage (sICH). MATERIALS AND METHODS: We retrospectively analyzed 102 patients with sICH who met the inclusion criteria, attending to Yongchuan Hospital of Chongqing Medical University from January 2019 to September 2020. Cranial CT within 6 h of onset was completed and repeated in 24 h. The volume and surface area of the hematoma are measured by software, and the relative surface area is calculated from the above data. The primary outcome was 90-day modified Rankin Scale(mRS) score, which was classified as good prognosis (≤2 points) and poor prognosis (>2 points) according to the results. Univariate analysis and binary logistic regression analysis were used to calculate the effect of each variable on poor prognosis. RESULTS: The study is comprised of 52 patients with favorable functional prognosis and 50 patients with unfavorable one. The findings showed that admission National Institutes of Health Stroke Scale(NIHSS), hematoma volume, relative surface area, hematoma expansion(HE) and serum calcium concentration were independent influencing factors for poor prognosis(P=0.004,0.007,0.023,0.001,0.035, respectively). ROC curve analysis revealed that the area under the curve of the relative surface area of the hematoma predicted poor prognosis was 0.894(95% CI 0.830-0.985, P<0.001), which was better than the rest of the variables. CONCLUSIONS: The relative surface area of hematoma in sICH is an independent risk factor for poor prognosis with a high predictive value, and large relative surface area suggests poor prognosis.

Protective Effect of Conditioned Media of Human Fetal Dermal Mesenchymal Stem Cells Can Inhibit Burn-induced Microvascular Hyperpermeability.

Burns often cause loss of skin barrier protection, fluid exudation, and local tissue edema, which hinder functional recovery. Effectively improving the quality of deep burn wound healing, shortening the wound healing time, and reducing tissue fluid leakage are urgent problems in the medical field. Human mesenchymal stem cells (MSCs) can effectively stabilize vascular endothelial injury. Fetal dermal MSCs (FDMSCs) are a newly discovered source of MSCs derived from the skin of accidentally aborted fetuses. However, the effect of FDMSCs on vascular permeability remains poorly understood. In this study, conditioned media from FDMSCs (F-CM) extracted from fetal skin tissue was prepared. The effect of F-CM on vascular permeability was evaluated using the internal circulation method FITC-dextran in vivo, and several in vitro assays, including cell viability assay, transwell permeability test, immunofluorescence, and western blotting. Altogether, our results demonstrate that F-CM could inhibit burn-induced microvascular hyperpermeability by increasing the protein expression levels of occludin and VE-cadherin, while restoring the expression of endothelial F-actin, and providing the foundation of a novel therapy for the treatment of burns with F-CM.

Impact of COVID-19 on Acute Stroke Presentation in a Designated COVID-19 Hospital.

Objectives: Thousands of designated COVID-19 hospitals have been set up in China to fight the ongoing COVID-19 pandemic. Anecdotal reports indicate a falling rate of acute stroke diagnoses in these hospitals during the COVID-19 period. We conducted an exploratory single-center analysis to estimate the change in acute stroke presentation at the designated COVID-19 hospitals. Methods: This retrospective observational study included all patients admitted to Yongchuan Hospital Affiliated to Chongqing Medical University with acute stroke between January 24 and March 10, 2020. Patient demographics, characteristics of the stroke, treatment details, and clinical outcomes were compared with those of patients admitted in the corresponding period in the year before (2019, "the pre-COVID-19 period"). Subgroup analysis was performed in the ischemic and hemorrhagic stroke groups. Results: A total of 110 patients presented with acute stroke symptoms during the COVID-19 pandemic, compared with 173 patients in the pre-COVID-19 period. A higher proportion of stroke patients presented to the hospital via emergency medical services during the pandemic (48.2 vs. 31.8%, p = 0.006). There was a lower proportion of ischemic stroke patients (50.9 vs. 65.3%, p = 0.016) than in the preceding year. There were significantly fewer patients with 90-day modified Rankin Scale score ≥3 in the COVID-19 period compared with the pre-COVID-19 period (17.3 vs. 30.6%, p = 0.012). Among patients with ischemic stroke, the mean time from patient arrival to vessel puncture for emergency endovascular therapy in the COVID-19 period was shorter than that in the pre-COVID-19 period (109.18 ± 71.39 vs. 270.50 ± 161.51 min, p = 0.002). Among patients with hemorrhagic stroke, the rate of emergency surgical operation in the COVID-19 period was higher than that in the pre-COVID-19 period (48.1 vs. 30.0%, p = 0.047). The mean time from patient arrival to emergency surgical operation (15.31 ± 22.89 vs. 51.72 ± 40.47 min, p = 0.002) was shorter in the COVID-19 period than in the pre-COVID-19 period. Conclusions: Although fewer acute stroke patients sought medical care in this designated COVID-19 hospital during the COVID-19 pandemic, this type of hospital was more efficient for timely treatment of acute stroke. Recognizing how acute strokes presented in designated COVID-19 hospitals will contribute to appropriate adjustments in strategy for dealing with acute stroke during COVID-19 and future pandemics.

The Natural History and Reperfusion Therapy Outcomes of Acute Ischemic Stroke due to Isolated M2 Occlusions.

OBJECTIVE: Currently, the standard treatment modality for patients with acute ischemic stroke (AIS) presenting with isolated M2 occlusions is not specific. We therefore assessed the difference in treatment outcomes for patients with isolated M2 occlusions. METHODS: We retrospectively analyzed consecutive patients with AIS presenting with isolated M2 occlusions from October 1, 2018, to June 30, 2020. Patients were divided into 3 groups based on the treatments they received: no reperfusion therapy (NRT), intravenous thrombolysis treatment (IVT), and endovascular intervention (EVT), which comprised IVT in conjunction with EVT or EVT alone. The primary outcomes were improvements in modified Rankin Scale (mRS) scores at 90 days and National Institutes of Health Stroke Scale (NIHSS) scores at 24 hours after treatment compared with the baseline. The secondary efficacy outcome comprised a good outcome rate defined as a 90 - day mRS score ≤ 2, final infarct volume (FIV), 90-day mortality rate, and successful recanalization rate, which was defined as a modified thrombolysis in cerebral infarction score ≥ 2b. Safety outcomes included symptomatic intracerebral hemorrhage and procedure-related complications. RESULTS: Seventy patients were enrolled and divided into 3 groups: the NRT group (n = 25), IVT group (n = 27), and EVT group (n = 18). Twenty-four-hour posttreatment NIHSS scores were substantially decreased by EVT compared with NRT (adjusted ß -4.01, 95% confidence interval [CI] -6.60 to -1.43; P = 0.003) or IVT (adjusted ß, -3.61 [95% CI, -6.45 to -0.77]; P = 0.013). Compared with the outcomes observed after NRT, patients who received EVT were more likely to achieve lower 90-day mRS scores (adjusted ß, -1.42 [95% CI, -2.66 to -0.63]; P = 0.007), higher good outcome rates (adjusted odds ratio, 8.73 [95% CI, 1.43-53.24]; P = 0.019), and smaller FIVs (adjusted ß, -29.66 [95% CI, -59.73 to 0.42]; P = 0.048). The recanalization rate of EVT was high (88.89%), and procedure-related complications were rare (5.56%). CONCLUSIONS: For acute, isolated M2 occlusions, EVT could dramatically and rapidly improve neurological deficits with high safety and effectiveness. These changes were observed at 24 hours after treatment and were maintained over the long term.

Prognostic value of cerebral infarction coefficient in patients with massive cerebral infarction.

OBJECTIVE: We proposed the concept of the cerebral infarction coefficient, which is cerebral infarction volume/brain volume. This study aimed to evaluate the prognostic value of the cerebral infarction coefficient in patients with massive cerebral infarction (MCI). METHODS: According to the modified Rankin score, 71 patients with acute MCI were divided into good prognosis and poor prognosis groups. Clinical and imaging data of the two groups were collected and univariate analysis was carried out. If there were significant differences in the data between the two groups, binary logistic regression analysis was performed. RESULTS: The poor prognosis group had a significantly higher cerebral infarction volume, cerebral infarction coefficient, and D-dimer levels, older age, the highest body temperature, a higher rate of a history of atrial fibrillation, and a lower rate of a history of hypertension compared with the good prognosis group (all P < 0.05). Binary logistic regression analysis showed that the cerebral infarction coefficient was an independent risk factor for a poor prognosis of patients with MCI (P < 0.05, 95 % confidence interval, 2.091, 42.562), and the odds ratio was 8.506. The area under the receiver operating characteristic curve for the cerebral infarction coefficient was 0.753. When the cut-off value was 7.8 %, the sensitivity of predicting a poor prognosis of patients with MCI was 92.5 %. CONCLUSION: The cerebral infarction coefficient may have predictive value in determining the prognosis of patients with MCI.

Fetal Dermal Mesenchymal Stem Cell-Derived Exosomes Accelerate Cutaneous Wound Healing by Activating Notch Signaling.

Fetal dermal mesenchymal stem cells (FDMSCs), isolated from fetal skin, are serving as a novel MSC candidate with great potential in regenerative medicine. More recently, the paracrine actions, especially MSC-derived exosomes, are being focused on the vital role in MSC-based cellular therapy. This study was to evaluate the therapeutic potential of exosomes secreted by FDMSCs in normal wound healing. First, the in vivo study indicated that FDMSC exosomes could accelerate wound closure in a mouse full-thickness skin wound model. Then, we investigated the role of FDMSC-derived exosomes on adult dermal fibroblast (ADFs). The results demonstrated that FDMSC exosomes could induce the proliferation, migration, and secretion of ADFs. We discovered that after treatment of exosomes, the Notch signaling pathway was activated. Then, we found that in FDMSC exosomes, the ligands of the Notch pathway were undetectable expect for Jagged 1, and the results of Jagged 1 mimic by peptide and knockdown by siRNA suggested that Jagged 1 may lead the activation of the Notch signal in ADFs. Collectively, our findings indicated that the FDMSC exosomes may promote wound healing by activating the ADF cell motility and secretion ability via the Notch signaling pathway, providing new aspects for the therapeutic strategy of FDMSC-derived exosomes for the treatment of skin wounds.

Antitumor effects of conditioned media of human fetal dermal mesenchymal stem cells on melanoma cells.

Background: Malignant melanoma is the most lethal form of cutaneous tumor and has a high metastatic rate and motility capacity. Owing to the poor prognosis, it is urgent to seek an effective therapeutic regimen. Human mesenchymal stem cells (MSCs) can home to tumor cells and have been shown to play important roles in both promoting and inhibiting tumor development. Fetal dermal MSCs (FDMSCs), derived from fetal skin are a novel source of MSCs. Nevertheless, the antitumor capacity of FDMSCs on malignant melanoma is not clearly understood. Materials and methods: FDMSCs were extracted from the dorsal skin of fetal tissues. A375 melanoma cells lines were obtained from American Type Culture Collection. The effects of conditioned media from FDMSCs (CM-FDMSC) on A375 melanoma cells were tested in vivo using tumor formation assay and in vitro using cell viability, 5-ethynyl-2'-deoxyuridine incorporation, flow cytometry, TdT-mediated dUTP Nick-End Labeling (TUNEL), wound healing, transwell invasion, and Western blotting. Results: CM-FDMSC inhibited A375 tumor formation in vivo. In vitro, CM-FDMSC inhibited the tumor-related activities of A375 melanoma cells, as evidenced reductions in viability, migration, and invasion. CM-FDMSC-treated A375 cells showed decreased phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and extracellular signal-regulated kinase (ERK) phosphorylation, and up-regulation of Bcl-2-Associated X (BAX) and down-regulation of B-cell lymphoma-2 (BCL-2) expression. Conclusion: CM-FDMSC can inhibit the tumor-forming behaviors of A375 melanoma cells and inhibit PI3K/AKT and mitogen-activated protein kinase signaling to shift their BCL-2/BAX ratio toward a proapoptotic state. Identification of the bioactive components in CM-FDMSC will be important for translating these findings into novel therapies for malignant melanoma.

Denatured acellular dermal matrix seeded with bone marrow mesenchymal stem cells for wound healing in mice.

It is the basic task of burn therapy to cover the wound with self-healthy skin timely and effectively. However, for patients with extensive burns, autologous skin is usually insufficient, and allogenic or heterogeneous skin leads to strong immune response. It is vital to choose an appropriate treatment for deep extensive burns. Nowadays, the dermal substitute combined with bone marrow mesenchymal stem cells (BM-MSCs) is a prospective strategy for burn wound healing. Denatured acellular dermal matrix (DADM), as one of dermal substitutes, which prepared by burn skin discarded in escharotomy, not only maintains a certain degree of 3D structure of collagen, but also has good biocompatibility. In this study, the preparation method of DADM was improved and DADM was seeded with BM-MSCs. Then BM-MSCs-seeded DADM (DADM/MSCs) was implanted into mice cutaneous wound, and the effect of DADM/MSCs dermal substitute was assessed on skin regeneration. As a result, BM-MSCs survived well and DADM/MSCs scaffolds significantly promoted wound healing in terms of angiogenesis, re-epithelialization and skin appendage regeneration. DADM/MSCs scaffold may represent an alternative promising therapy for wound healing in deep extensive burns.

Interleukin 17 (IL-17)-Induced Mesenchymal Stem Cells Prolong the Survival of Allogeneic Skin Grafts.

BACKGROUND Mesenchymal stem cells (MSCs) have the potential of self-renewal and multi-differentiation and have a wide application prospect in organ transplantation for the effect of inducing immune tolerance. It has found that interleukin 17 (IL-17) could enhance the inhibition effect of MSCs on T cell proliferation and increase the immunosuppressive effect of MSCs. In this study, we aimed to investigate the effect of IL-17-induced MSCs on allograft survival time after transplantation. MATERIAL AND METHODS BMSCs were characterized by differential staining. The allogenic skin transplantations were performed and the BMSCs pre-treated by IL-17 were injected. To assess the immunosuppressive function of IL-17-induced BMSCs, the morphology of the grafts, the homing ability of the BMSCs, and the survival time of the grafts were analyzed. RESULTS BMSCs from BALB/c have multidirectional differentiation potential to differentiate into osteogenic, chondrogenic, and adipogenic lineage cells. IL-17-induced BMSCs prolonged the survival time of allogeneic skin grafts dramatically. We found that there were more labeled MSCs in the skin grafts, and the Treg subpopulations percentage, IL-10, and TGF-ß were significantly increased, while the IFN-γ level was decreased compared to the control group and MSCs group. In conclusion, IL-17 can enhance the homing ability of MSCs and regulate the immunosuppressive function of MSC. CONCLUSIONS Our data demonstrate that IL-17 plays the crucial role in MSC homing behaviors and promotes immunosuppression of MSCs during transplantation procedures, suggesting that IL-17-pre-treated MSCs have potential to prolong graft survival and reduce transplant rejection.

Inhibiting function of human fetal dermal mesenchymal stem cells on bioactivities of keloid fibroblasts.

BACKGROUND: Keloid is one kind of benign skin disease caused by hyperplasia of fibroblasts and collagen fibrils. It is refractory due to the lack of an effective treatment at present, which puts pressure on seeking a new therapeutic regimen. Mesenchymal stem cells (MSCs) from fetal skin are considered to play a crucial role in scarless healing. Nevertheless, the efficacy of them in keloid disorders remains poorly understood. METHODS: Keloid fibroblasts (KFs), human adult dermal fibroblasts (ADFs), and human fetal dermal mesenchymal stem cells (FDMSCs) were isolated to single cells and cultured in Dulbecco's modified Eagle's medium (DMEM). ADFs and FDMSCs were used to generate ADF-conditioned medium (A-CM) and FDMSC-conditioned medium (F-CM). The effects of A-CM and F-CM on KFs were tested using MTT assay, BrdU assay, TUNEL assay, quantitative polymerase chain reaction, Western blot, and annexin V-FITC/PI binding assay,. RESULTS: FDMSCs inhibited the bioactivity of KFs, downregulated the expression of the antiapoptotic protein BCL-2, and upregulated the expression of the proapoptotic protein BAX of KFs by secreting some soluble substances, thus accelerating the apoptosis of KFs. CONCLUSION: F-CM induces apoptosis of KFs, providing a novel treatment strategy for keloid disorders.