Rates and Impact of Serious Adverse Events after Endovascular Thrombectomy among Large Vessel Occlusion Stroke Patients.

Objective Complications or serious adverse events (SAEs) are common in the treatment of patients with large vessel occlusion stroke. There has been limited study of the impact of SAEs for patients after endovascular thrombectomy (EVT). The goal of this study was to characterize the rates and clinical impact of SAEs following EVT. Methods A post-hoc analysis was performed using pooled databases of the 'DEVT' and 'RESCUE BT' trials. SAEs were designated as symptomatic intracranial hemorrhage, brain herniation or craniectomy, respiratory failure, circulatory failure, pneumonia, deep venous thrombosis, and systemic bleeding. The primary endpoint was functional independence (modified Rankin Scale score 0-2 within 90 days). Logistic regression analysis was used to determine the predictors and associations between SAEs and outcomes. Results Of 1182 enrolled patients, 402 (34%) had a procedural complication, 745 (63%) had 1404 SAEs occurrences with 4.65% in-hospital mortality. The three most frequent SAEs were pneumonia (620, 52.5%), systemic bleeding (174, 14.7%) and respiratory failure (173, 14.6%). Pneumonia, systemic bleeding or deep venous thrombosis were less life-threatening. Patients with advanced age (adjusted odds ratio, 1.28 [95% confidence interval, 1.14-1.43]), higher NIHSS (1.09 [1.06-1.11]), occlusion site (middle cerebral artery-M1 vs. intracranial cerebral artery [ICA]: 0.75 [0.53-1.04]; M2 vs. ICA: 1.30 [0.80-2.12]), longer procedure time (1.01 [1.00-1.01]) and unsuccessful vessel recanalization (1.79 [1.06-2.94]) were more likely to experience SAEs. Compared with no SAE, patients with SAEs had lower odds of functional independence (0.46 [0.40-0.54]). Conclusions Overall, SAEs diagnosed following thrombectomy in patients with stroke were common (more than 60%) and associated with functional dependence. Patients with advanced age, higher NIHSS, longer procedure time and failed recanalization were more likely to experience SAEs. There was no statistical difference in the risk of SAEs among patient with M1 and M2 occluded compared with those ICA occluded. An understanding of the prevalence and predictors of SAEs could alert clinicians to the estimated risk of an SAE for a patient after EVT.

Expert Consensus on the Application of Stem Cells in Psoriasis Research and Clinical Trials.

Psoriasis is an immune-mediated, chronic, relapsing, inflammatory, systemic disease induced by individual-environmental interactions, and is often lifelong because of the difficulty of treatment. In recent years, a variety of targeted therapies, including biologics, have improved the lesions and quality of life of most psoriasis patients, but they still do not address the problem of relapse and may be associated with decreased efficacy or adverse events such as infections over time. Therefore, there is an urgent need for breakthroughs in psoriasis treatment and in relapse-delaying and non-pharmacologic strategies, and stem cell therapy for psoriasis has emerged. In recent years, research on stem cell therapy for psoriasis has received a lot of attention, however, there is no reference standard as well as consensus in this field of research. Therefore, according to the latest consensus and guidelines, combined with relevant literature reports, clinical practice experience and the results of discussions with experts, this consensus specifies the types of stem cells commonly used in the treatment of psoriasis, the methods, dosages, and routes of stem cell therapy for psoriasis, as well as the clinical evaluations (efficacy and safety) of stem cell therapy for psoriasis. In addition, this consensus also provides normative standards for the processes of collection, preparation, preservation and quality control of stem cells and their related products, as well as recommendations for the management of stem cells during infusion for the treatment of psoriasis. This consensus provides the latest specific reference standards and practice guidelines for the field of stem cell therapy for psoriasis.

Flexible Sono-Piezo Patch for Functional Sweat Gland Repair through Endogenous Microenvironmental Remodeling.

Remodeling the endogenous regenerative microenvironment in wounds is crucial for achieving scarless, functional tissue regeneration, especially the functional recovery of skin appendages such as sweat glands in burn patients. However, current approaches mostly rely on the use of exogenous materials or chemicals to stimulate cell proliferation and migration, while the remodeling of a pro-regenerative microenvironment remains challenging. Herein, we developed a flexible sono-piezo patch (fSPP) that aims to create an endogenous regenerative microenvironment to promote the repair of sweat glands in burn wounds. This patch, composed of multifunctional fibers with embedded piezoelectric nanoparticles, utilized low-intensity pulsed ultrasound (LIPUS) to activate electrical stimulation of the target tissue, resulting in enhanced pro-regenerative behaviors of niche tissues and cells, including peripheral nerves, fibroblasts, and vasculatures. We further demonstrated the effective wound healing and regeneration of functional sweat glands in burn injuries solely through such physical stimulation. This noninvasive and drug-free therapeutic approach holds significant potential for the clinical treatment of burn injuries.

Nurses' health education competence and health literacy: A cross-sectional survey in Chinese county hospitals.

AIM: This study aims to assess the health education competence of nurses in China's county hospitals, examining its relationship with health literacy and other influencing factors, such as receipt of health education training, and acquisition of health knowledge. BACKGROUND: Nurses are pivotal in delivering health education, which is crucial for improving health outcomes. In rural China, the prevalent low health literacy, stemming from limited access to health guidance, necessitates an evaluation of nurses' health education competence in county hospitals. Understanding these competencies and their influencing factors is essential to enhance the health literacy of the Chinese population. DESIGN: A cross-sectional study. METHODS: The study surveyed 692 nurses from nine county hospitals in Shanxi Province, China, using convenience sampling. The analysis employed descriptive statistics, t-tests, ANOVA, Pearson's correlation, and hierarchical multiple linear regression. RESULTS: The study revealed a low level of health education competence among the surveyed nurses, with total health education scores averaging 3.77±0.60, and mean scores for knowledge, skills, and attitudes being 3.73±0.67, 3.77±0.64, and 3.89±0.64, respectively. The multiple regression models were significant (P<0.001), with R2 values ranging from 0.143 to 0.197. Key predictors included the incentive mechanism for health education, receipt of health education training, acquisition of health knowledge, and literacies in infectious disease prevention, scientific health concepts, and chronic disease prevention. CONCLUSIONS: This study assessed the health education competence of nurses in county hospitals in China and investigated the impact of various dimensions of health literacy on this competence. The findings indicate that the health education competence of nurses in these settings remains relatively low. Additionally, health education training and incentive mechanisms were found to significantly enhance nurses' health education competence in areas lacking medical resources.

Quercetin alleviates kidney damage caused by mercury Chloride: The protective effects of quercetin on autophagy and inflammation were studied based on TRIM32/TLR4/LC3 pathway.

OBJECTIVE: Mercury is one of the heavy metal pollutants causing serious harm to human health. Quercetin was observed to repair kidney damage through the TLR4/TRIM32 pathway, and the detoxification effect of quercetin on heavy metal poisoning was observed. METHODS: For the study, the researchers divided 40 male mice from the KM strain into five groups: control, HgCl2, QU30, HgCl2+QU15, and HgCl2+QU30. The biological effects of those mice in each group were detected by the biochemical experiment, histopathology experiment and protein expression experiment respectively. RESULTS: HgCl2 had effects in increasing the level of malondialdehyde (MDA) and decreasing the activity of antioxidant enzymes (P < 0.05). HgCl2 induced inflammation by increasing tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and Toll Like Receptor 4 (TLR-4) (P < 0.05). The expression of creatinine (CRE) and urea nitrogen (BUN) showed that HgCl2 promoted kidney injury. HgCl2 altered renal tissue integrity and TRIM32 expression which resulted in the increased autophagy associated protein levels of LC3. In contrast, quercetin reduced oxidative stress, autophagy, inflammation and histopathological changes (P < 0.05). CONCLUSION: Quercetin has the renal protection effects of anti-inflammation, anti-oxidation and anti-autophagy.

Expert Consensus on Prevention and Treatment of Aging-Related Gonadal Dysfunction.

Aging-related hypogonadism involves complex mechanisms in humans, predominantly relating to the decline of multiple hormones and senile gonads. Late-onset hypogonadism (LOH) and erectile dysfunction (ED) are the main manifestations in men, while premature ovarian insufficiency (POI) and menopause are the main forms in women. Anti-aging measures include lifestyle modification and resistance training, hormonal supplementation, stem cell therapy, metformin, and rapamycin. In this expert consensus, the mechanisms, efficacy, and side effects of stem cell therapy on aging gonadal function are reviewed. Furthermore, various methods of stem cell therapy, administered intravenously, intracavernously, and intra-ovarially, are exemplified in detail. More clinical trials on aging-related gonadal dysfunction are required to solidify the foundation of this topic.

Efficacy and Safety of 5-Aminolevulinic Acid Photodynamic Therapy for Treating Cervical and Vaginal Intraepithelial Neoplasia.

Persistent HPV infections may cause cervical and vaginal intraepithelial neoplasia (CIN and VaIN). Traditional methods might destroy the structure and function of the cervix. 5-aminolevulinic acid photodynamic therapy (ALA-PDT) is a non-invasive targeted therapy. This study aims to evaluate the efficacy and safety of ALA-PDT for CIN and VaIN and the clearance of HPV. A retrospective study of 303 patients who confirmed CIN or VaIN and received ALA-PDT was conducted. All the patients were followed up at six and twelve months after treatment and then annually thereafter. The effect was evaluated through HPV genotyping, a cytology test, and colposcopy-directed biopsy if necessary. After ALA-PDT, the remission rates for CIN 2, CIN 3, VaIN 2, and VaIN 3 were 90.6%, 88.5%, 87.3%, and 77.8%. For CIN 1, the remission rate at the six-month follow-up was 93.1%. The total HPV clearance rates were 72.5% at the six-month follow-up and 85.7% at the 12-month follow-up. The most common adverse event was vaginal discharge. No severe adverse effect was observed. ALA-PDT is an effective and safe treatment for all grades of CIN and VaIN and is helpful in clearing HPV with minimal side effects. This treatment may not influence fertility and delivery.

Decompressive craniectomy for patients with malignant infarction of the middle cerebral artery: A pooled analysis of two randomized controlled trials.

BACKGROUND: Decompressive craniectomy (DC) reduces mortality without increasing the risk of very severe disability among patients with life-threatening massive cerebral infarction. However, its efficacy was demonstrated before the era of endovascular thrombectomy trials. It remains uncertain whether DC improves the prognosis of patients with malignant middle cerebral artery (MCA) infarction receiving endovascular therapy. METHODS: We pooled data from two trials (DEVT and RESCUE BT studies in China) and patients with malignant MCA infarction were included to assess outcomes and heterogeneity of DC therapy effect. Patients with herniation were dichotomized into DC and conservative groups according to their treatment strategy. The primary outcome was the rate of mortality at 90 days. Secondary outcomes included disability level at 90 days as measured by the modified Rankin Scale score (mRS) and quality-of-life score. The associations of DC with clinical outcomes were performed using multivariable logistic regression. RESULTS: Of 98 patients with herniation, 37 received DC surgery and 61 received conservative treatment. The median (interquartile range) was 70 (62-76) years and 40.8% of the patients were women. The mortality rate at 90 days was 59.5% in the DC group compared with 85.2% in the conservative group (adjusted odds ratio, 0.31 [95% confidence interval (CI), 0.10-0.94]; P=0.04). There were 21.6% of patients in the DC group and 6.6% in the conservative group who had a mRS score of 4 (moderately severe disability); and 10.8% and 4.9%, respectively, had a score of 5 (severe disability). The quality-of-life score was higher in the DC group (0.00 [0.00-0.14] vs 0.00 [0.00-0.00], P=0.004), but DC treatment was not associated with better quality-of-life score in multivariable analyses (adjusted ß Coefficient, 0.02 [95% CI, -0.08-0.11]; p=0.75). CONCLUSIONS: DC was associated with decreased mortality among patients with malignant MCA infarction who received endovascular therapy. The majority of survivors remained moderately severe disability and required improvement on quality of life. CLINICAL TRIAL REGISTRATION: The DEVT trial: http://www.chictr.org. Identifier, ChiCTR-IOR-17013568. The RESCUE BT trial: URL: http://www.chictr.org. Identifier, ChiCTR-INR-17014167.

Anlotinib may enhance the efficacy of anti-PD1 therapy by inhibiting the AKT pathway and promoting the apoptosis of CAFs in lung adenocarcinoma.

Although PD-1 inhibitors have revolutionized the treatment paradigm of non-small cell lung cancer (NSCLC), their efficacy in treating NSCLC has remained unsatisfactory. Targeting cancer-associated fibroblasts (CAFs) is a potential approach for improving the immunotherapy response. Multitarget antiangiogenic tyrosine kinase receptor inhibitors (TKIs) can enhance the efficacy of PD-1 inhibitors in NSCLC patients. However, the effects and mechanisms of antiangiogenic TKIs on CAFs have not been elucidated. In this study, we first compared anlotinib with other antiangiogenic TKIs and confirmed the superior efficacy of anlotinib. Furthermore, we established NSCLC-associated CAF models and found that anlotinib impaired CAF viability and migration capacity and contributed to CAF apoptosis and cell cycle arrest in the G2/M phase. Moreover, anlotinib treatment attenuated the capacity of CAFs to recruit lung cancer cells and macrophages. Experiments in animal models suggested that anlotinib could enhance the efficacy of anti-PD1 therapy in NSCLC and affect CAF proliferation and apoptosis. Anlotinib increased the abundance of tumor-infiltrating CD8 + T cells, and PD-1 inhibitor-induced cytotoxicity to tumor cells was achieved through the transformation of the tumor microenvironment (TME) caused by anlotinib, which may partly explain the synergistic antitumor effect of anlotinib and PD-1 inhibitors. Mechanistically, anlotinib affects CAF apoptosis and cell viability at least in part by inhibiting the AKT pathway. In conclusion, our study suggested that anlotinib could regulate the TME, inhibit the AKT pathway and promote CAF apoptosis, providing new insights into the antitumor effect of anlotinib and improving the efficacy of immunotherapy.

Self-Assembled DNA Composite-Engineered Mesenchymal Stem Cells for Improved Skin-Wound Repair.

The direct use of mesenchymal stem cells (MSCs) as therapeutics for skin injuries is a promising approach, yet it still faces several obstacles, including limited adhesion, retention, and engraftment of stem cells in the wound area, as well as impaired regenerative and healing functions. Here, DNA-based self-assembled composites are reported that can aid the adhesion of MSCs in skin wounds, enhance MSC viability, and accelerate wound closure and re-epithelialization. Rolling-circle amplification (RCA)-derived DNA flowers, equipped with multiple copies of cyclic Arg-Gly-Asp (cRGD) peptides and anti-von Willebrand factor (vWF) aptamers, act as robust scavengers of reactive oxygen species (ROS) and enable synergistic recognition and adhesion to stem cells and damaged vascular endothelial cells. These DNA structure-aided stem cells are retained at localized wound sites, maintain repair function, and promote angiogenesis and growth factor secretion. In both normal and diabetes-prone db/db mice models with excisional skin injuries, facile topical administration of DNA flower-MSCs elicits rapid blood vessel formation and enhances the sealing of the wound edges in a single dose. DNA composite-engineered stem cells warrant further exploration as a new strategy for the treatment of skin and tissue damage.

Clinical Decision Support System Used in Spinal Disorders: Scoping Review.

BACKGROUND: Spinal disorders are highly prevalent worldwide with high socioeconomic costs. This cost is associated with the demand for treatment and productivity loss, prompting the exploration of technologies to improve patient outcomes. Clinical decision support systems (CDSSs) are computerized systems that are increasingly used to facilitate safe and efficient health care. Their applications range in depth and can be found across health care specialties. OBJECTIVE: This scoping review aims to explore the use of CDSSs in patients with spinal disorders. METHODS: We used the Joanna Briggs Institute methodological guidance for this scoping review and reported according to the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) statement. Databases, including PubMed, Embase, Cochrane, CINAHL, Web of Science, Scopus, ProQuest, and PsycINFO, were searched from inception until October 11, 2022. The included studies examined the use of digitalized CDSSs in patients with spinal disorders. RESULTS: A total of 4 major CDSS functions were identified from 31 studies: preventing unnecessary imaging (n=8, 26%), aiding diagnosis (n=6, 19%), aiding prognosis (n=11, 35%), and recommending treatment options (n=6, 20%). Most studies used the knowledge-based system. Logistic regression was the most commonly used method, followed by decision tree algorithms. The use of CDSSs to aid in the management of spinal disorders was generally accepted over the threat to physicians' clinical decision-making autonomy. CONCLUSIONS: Although the effectiveness was frequently evaluated by examining the agreement between the decisions made by the CDSSs and the health care providers, comparing the CDSS recommendations with actual clinical outcomes would be preferable. In addition, future studies on CDSS development should focus on system integration, considering end user's needs and preferences, and external validation and impact studies to assess effectiveness and generalizability. TRIAL REGISTRATION: OSF Registries osf.io/dyz3f; https://osf.io/dyz3f.

Intravenous Tirofiban Versus Alteplase Before Endovascular Treatment in Acute Ischemic Stroke: A Pooled Analysis of the DEVT and RESCUE BT Trials.

BACKGROUND: The present study aimed to evaluate the efficacy and safety of intravenous tirofiban versus alteplase before endovascular treatment (EVT) in acute ischemic stroke patients with intracranial large vessel occlusion. METHODS: This was a post hoc analysis using data from 2 multicenter, randomized trials: the DEVT trial (Direct Endovascular Treatment for Large Vessel Occlusion Stroke) from May 2018 to May 2020 and the RESCUE BT trial (Intravenous Tirofiban Before Endovascular Thrombectomy for Acute Ischemic Stroke) from October 2018 to October 2021. Patients with acute intracranial large vessel occlusion within 4.5 hours from last known well were dichotomized into 2 groups: tirofiban plus EVT versus alteplase bridging with EVT. The primary outcome was functional independence (modified Rankin Scale score of 0-2) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage and 3-month mortality. Multivariable logistic regression (adjusting for baseline systolic blood pressure, occlusion site, onset-to-puncture time, anesthesia, and first choice of EVT) and propensity score overlap weighting (balance in demographic covariates, stroke characteristics, and initial management between groups) were performed. RESULTS: One-hundred and eighteen alteplase-treated patients in the DEVT trial and 98 tirofiban-treated patients in the RESCUE BT trial were included (median age, 70 years; 115 [53.2%] men). The rate of functional independence was 60.2% in the tirofiban group compared with 46.6% in the alteplase group (adjusted odds ratio, 1.25 [95% CI, 0.60-2.63]). Compared with alteplase, tirofiban was not associated with increased risk of symptomatic intracranial hemorrhage (6.8% versus 9.2%; P=0.51) and mortality (17.8% versus 19.4%; P=0.76). The propensity score overlap weighting analyses showed consistent outcomes. CONCLUSIONS: Among patients with intracranial large vessel occlusion within 4.5 hours of onset, tirofiban plus EVT was comparable to alteplase bridging with EVT regarding the efficacy and safety outcomes. These findings should be interpreted as preliminary and require confirmation in a randomized trial. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifiers: ChiCTR-IOR-17013568 and ChiCTR-INR-17014167.

Percent body fat was negatively correlated with Testosterone levels in male.

BACKGROUND: Lower testosterone levels in men have been consistently associated with metabolic abnormalities, particularly obesity. This study aims to investigate the relationship between testosterone and obesity by analyzing the correlation between testosterone levels and body fat percentage using data from the NHANES (National Health and Nutrition Examination Survey) database. METHODS: The study included a total of 5959 participants from the NHANES 2011-2016. Multivariable linear regression models were used to assess the association between testosterone levels and body composition parameters, including total percent fat (TPF), android percent fat (APF), gynoid percent fat (GPF), android to gynoid ratio (A/G), and lean mass percent (LMP). Subgroup analyses stratified by sex were conducted using multivariable linear regression. To account for potential non-linear relationships, fitted smoothing curves and generalized additive models were utilized. A separate analysis of participants with a BMI ≥ 30 kg/m2 was conducted to validate the conclusions. RESULT: Among males, testosterone levels showed a significant negative correlation with TPF (ß = -11.97, P <0.0001), APF (ß = -9.36, P<0.0001), GPF (ß = -10.29, P <0.0001), and A/G (ß = -320.93, P<0.0001), while a positive correlation was observed between LMP and testosterone levels (ß = 12.62, P<0.0001). In females, a contrasting pattern emerged in the relationship between testosterone and body fat, but no significant correlation was found between testosterone and body composition in obese women. CONCLUSIONS: The findings of this study support a negative association between body fat and testosterone levels in males.

GmRj2/Rfg1 control of soybean-rhizobium-soil compatibility.

Coordinated evolution and mutual adaptation of soybean-rhizobium-soil (SRS) are crucial for soybean distribution, but the genetic mechanism involved had remained unclear. In a recent study, Li et al. identified a natural variant of the GmRj2/Rfg1 gene that affected the ability of soybean to adapt to distinct soil types by controlling soybean-rhizobium interaction, thus unravelling the mystery of SRS compatibility.

Identifying clinical features and molecular characteristics of the endometrial clear cell carcinoma.

Objective: The aim of this study was to verify TCGA subtypes in endometrial clear cell carcinoma (ECCC) and determine their clinical and molecular characteristics. Methods: We summarized and compared the clinical features of 28 clear cell carcinoma and 112 endometrioid carcinoma patients. Of the 28 ECCCs, 19 underwent TCGA classification, and other markers (ER, PR, ARID1A, ARIB1B, TAF1, and HER-2) were also detected by IHC, and outcomes were assessed. Results: Compared to endometrioid carcinoma, ECCC had an older age of onset (median age, 64.5 years, range 31-81 years), higher rate of myometrial invasion (42.8% vs. 21.5% in endometrioid carcinoma), LVSI (33% vs. 16%), and more advanced FIGO stage. Among the ECCCs, LVSI was a poor prognostic factor. TCGA classification was performed for 19 ECCCs: two POLEmut cases (10.5%), three MMRd (15.8%), 11 p53wt (57.9%), and three p53abn (15.8%). Of the 19 ECCCs, six (31.6%) showed HER-2 positive expression, and eight (42.1%) had TAF1 expression loss. ECCCs possessed HER-2 and TAF1 expression had worse outcomes. Conclusion: Our study summarized the clinical features of ECCC. The outcomes of patients with ECCC with TCGA subtypes differed from those of patients with endometrioid carcinoma. HER-2 and TAF1 may be new prognostic factors.

Recent advancement in vascularized tissue-engineered bone based on materials design and modification.

Bone is one of the most vascular network-rich tissues in the body and the vascular system is essential for the development, homeostasis, and regeneration of bone. When segmental irreversible damage occurs to the bone, restoring its vascular system by means other than autogenous bone grafts with vascular pedicles is a therapeutic challenge. By pre-generating the vascular network of the scaffold in vivo or in vitro, the pre-vascularization technique enables an abundant blood supply in the scaffold after implantation. However, pre-vascularization techniques are time-consuming, and in vivo pre-vascularization techniques can be damaging to the body. Critical bone deficiencies may be filled quickly with immediate implantation of a supporting bone tissue engineered scaffold. However, bone tissue engineered scaffolds generally lack vascularization, which requires modification of the scaffold to aid in enhancing internal vascularization. In this review, we summarize the relationship between the vascular system and osteogenesis and use it as a basis to further discuss surgical and cytotechnology-based pre-vascularization strategies and to describe the preparation of vascularized bone tissue engineered scaffolds that can be implanted immediately. We anticipate that this study will serve as inspiration for future vascularized bone tissue engineered scaffold construction and will aid in the achievement of clinical vascularized bone.

Engineered extracellular vesicles for ischemic stroke: a systematic review and meta-analysis of preclinical studies.

BACKGROUND: This systematic review and meta-analysis aimed to evaluate the efficacy of engineered extracellular vesicles (EEVs) in the treatment of ischemic stroke (IS) in preclinical studies and to compare them with natural extracellular vesicles (EVs). The systematic review provides an up-to-date overview of the current state of the literature on the use of EEVs for IS and informs future research in this area. METHODS: We searched PubMed, EMBASE, Web of Science, Cochrane Library, and Scopus databases for peer-reviewed preclinical studies on the therapeutic effect of EEVs on IS.Databases ranged from the inception to August 1, 2023. The outcome measures included infarct volumes, neurological scores, behavioral scores, apoptosis rates, numbers of neurons, and levels of IL-1ß, IL-6, and TNF-α. The CAMARADES checklist was used to assess the quality and bias risks of the studies. All statistical analyses were performed using RevMan 5.4 software. RESULTS: A total of 28 studies involving 1760 animals met the inclusion criteria. The results of the meta-analysis showed that compared to natural EVs, EEVs reduced infarct volume (percentage: SMD = -2.33, 95% CI: -2.92, -1.73; size: SMD = -2.36, 95% CI: -4.09, -0.63), improved neurological scores (mNSS: SMD = -1.78, 95% CI: -2.39, -1.17; Zea Longa: SMD = -2.75, 95% CI: -3.79, -1.71), promoted behavioral recovery (rotarod test: SMD = 2.50, 95% CI: 1.81, 3.18; grid-walking test: SMD = -3.45, 95% CI: -5.15, -1.75; adhesive removal test: SMD = -2.60, 95% CI: -4.27, -0.93; morris water maze test: SMD = -3.91, 95% CI: -7.03, -0.79), and reduced the release of proinflammatory factors (IL-1ß: SMD = -2.02, 95% CI: -2.77, -1.27; IL-6: SMD = -3.01, 95% CI: -4.47, -1.55; TNF-α: SMD = -2.72, 95% CI: -4.30, -1.13), increasing the number of neurons (apoptosis rate: SMD = -2.24, 95% CI: -3.32, -1.16; the number of neurons: SMD = 3.70, 95% CI: 2.44, 4.96). The funnel plots for the two main outcome measures were asymmetric, indicating publication bias. The median score on the CAMARADES checklist was 7 points (IQR: 6-9). CONCLUSIONS: This meta-analysis shows that EEVs are superior to natural EVs for the treatment of IS. However, research in this field is still at an early stage, and more research is needed to fully understand the potential therapeutic mechanism of EEVs and their potential use in the treatment of IS. PROSPERO REGISTRATION NUMBER: CRD42022368744.

Exosomes from human adipose-derived mesenchymal stem cells attenuate localized scleroderma fibrosis by the let-7a-5p/TGF-ßR1/Smad axis.

BACKGROUND: Inflammation and fibrosis of the skin are characteristics of localized scleroderma (LS). Emerging evidence has demonstrated that exosomes from human adipose tissue-derived mesenchymal stem cells (ADSC-Exo) could alleviate skin fibrosis. OBJECTIVE: The impact and potential mechanism of ADSC-Exo on LS fibrosis was examined. METHODS: ADSC-Exo was isolated and identified. The effects of ADSC-Exo on the abilities of proliferation and migration of LS-derived fibroblasts (LSFs) were assessed by CCK-8 and scratch assays, respectively. qRT-PCR, western blot, and immunofluorescence were conducted to detect LSFs stimulated with ADSC-Exo, ADSC-ExoAnti-let-7a-5p, let-7a-5p mimic/TGF-ßR1 shRNA virus, and negative controls. The impact of ADSC-Exo on C57BL/6j LS mice was evaluated by photographic morphology, hematoxylin-eosin (H&E), Masson's trichrome, and immunohistochemical staining. RESULTS: The verified ADSC-Exo limited the proliferation and migration of LSFs and reduced the expression of COL1, COL3, α-SMA, TGF-ßR1, and p-Smad2/ 3 in vitro and in vivo. TGF-ßR1 knockdown and let-7a-5p mimic in LSFs reduced the expression of COL1, COL3, α-SMA, and p-Smad2/3. However, compared with the ADSC-ExoNC group, the dermal thickness was increased, collagen arrangement was disordered, and α-SMA and TGF-ßR1 levels were increased after exposure to ADSC-ExoAnti-let-7a-5p. CONCLUSIONS: In this study, it might show that ADSC-Exo may successfully prevent LSF bioactivity, collagen deposition, and myofibroblast trans-differentiation. Additionally, we confirmed that let-7a-5p in ADSC-Exo could directly target TGF-R1 to control the Smad pathway and reduce fibrosis in LSFs. Our work offered a brand-new therapeutic approach and clarified the unique mechanism for the clinical management of LS.

New perspective on the immunomodulatory activity of ginsenosides: Focus on effective therapies for post-COVID-19.

More than 700 million confirmed cases of Coronavirus Disease-2019 (COVID-19) have been reported globally, and 10-60% of patients are expected to exhibit "post-COVID-19 symptoms," which will continue to affect human life and health. In the absence of safer, more specific drugs, current multiple immunotherapies have failed to achieve satisfactory efficacy. Ginseng, a traditional Chinese medicine, is often used as an immunomodulator and has been used in COVID-19 treatment as a tonic to increase blood oxygen saturation. Ginsenosides are the main active components of ginseng. In this review, we summarize the multiple ways in which ginsenosides affect post-COVID-19 symptoms, including inhibition of lipopolysaccharide, tumor necrosis factor signaling, modulation of chemokine receptors and inflammasome activation, induction of macrophage polarization, effects on Toll-like receptors, nuclear factor kappa-B, the mitogen-activated protein kinase pathway, lymphocytes, intestinal flora, and epigenetic regulation. Ginsenosides affect virus-mediated tissue damage, local or systemic inflammation, immune modulation, and other links, thus alleviating respiratory and pulmonary symptoms, reducing the cardiac burden, protecting the nervous system, and providing new ideas for the rehabilitation of patients with post-COVID-19 symptoms. Furthermore, we analyzed its role in strengthening body resistance to eliminate pathogenic factors from the perspective of ginseng-epidemic disease and highlighted the challenges in clinical applications. However, the benefit of ginsenosides in modulating organismal imbalance post-COVID-19 needs to be further evaluated to better validate the pharmacological mechanisms associated with their traditional efficacy and to determine their role in individualized therapy.