BACKGROUND:Exosomes play a role in all stages of wound repair,and there is currently a large body of research on exosomes in skin wound repair,which has been shown to have great potential for clinical applications. OBJECTIVE:To summarize and discuss the main mechanisms and clinical applications of exosomes in the treatment of skin wounds,in order to promote the clinical translation of exosomes. METHODS:PubMed,clinicaltrials.gov,China National Knowledge Infrastructure,Food and Drug Administration database,and Chinese Clinical Trial Register were searched from inception to March 2023.The English search terms were"exosomes,wound healing,stem cells,chronic wound,immunoregulation,inflammation,skin,therapeutic use,isolation,characterization,infections".The Chinese search terms were"exosomes,wound healing,stem cells,immunomodulation,clinical applications".A total of 79 articles were included for the summary. RESULTS AND CONCLUSION:(1)Exosomes can improve and accelerate wound healing through inflammation regulation,immune protection,angiogenesis,cell proliferation and migration,and collagen remodeling.(2)Exosomes derived from stem cells have mature preparation techniques and related mechanism research,which is currently the mainstream research direction.Non-stem cell-derived exosomes have the advantages of convenience,economy,and easy production,and can be used as a supplement for clinical applications.(3)The clinical application of exosomes is still in its infancy,but has great potential for application.Various exosome modification techniques have laid the foundation for the future development of clinically personalized services and require further research.(4)The clinical translation of exosomes faces many challenges,such as low yield,high heterogeneity,lack of unified standards for isolation,purification,and quality control,and difficulties in storage.

Objective To analyze the basic case data and laboratory test index characteristics of patients with myasthenia gravis(MG),so as to evaluate the application value of common clinical laboratory indicators in the construction of a diagnostic model for MG.Methods A retrospective analysis was performed on the basic data and laboratory indicators of MG patients and gender and age-matched healthy controls diagnosed at Beijing Tiantan Hospital,Capital Medical University from April 2021 to April 2023.A diagnostic model was constructed,and the receiver operating characteristic(ROC)curve was drawn to analyze the area under the curve(AUC).Results The BMI,heart rate,systolic blood pressure,and diastolic blood pressure in the MG group were significantly higher than those in the control group,with statistical significance(P＜0.05).There were significant differences in total protein,albumin,white blood cell count,proportion of large platelets,abso-lute value of monocyte and triiodothyronine between MG group and control group(P＜0.05).Seven indexes of heart rate,diastolic blood pressure,albumin,creatine kinase,cholinesterase,triglyceride and apolipoprotein B were selected to construct the diagnostic model.The area under the curve of the combined application of multiple indexes could reach 0.995,with a sensitivity and specificity of 97.60％and 96.10％,respectively.Conclusion In this study,the laboratory test indexes that can be used for the diagnosis of MG are successfully selected,and the sensitivity and specificity of the combined application of multiple indexes are high,which can be used for the auxiliary diagnosis of MG.

Objective:To investigate the relationship between CYP2C19, UGT1A1 gene polymorphisms and tamoxifen therapy in breast cancer patients.Methods:A total of 100 breast cancer patients diagnosed and treated in our hospital from Feb. 2021 to Mar. 2023 were chosen and given tamoxifen treatment after surgery. Polymerase chain reaction (PCR) was used to detect CYP2C19 and UGT1A1 gene polymorphisms, and the relationship between CYP2C19, UGT1A1 gene polymorphisms and tamoxifen treatment effect was analyzed.Results:In 100 patients with breast cancer, the distribution frequencies of CYP2C19 wild type (G/G) and mutant type (G/A, A/A) were 49.00% and 51%, respectively; The distribution frequencies of wild type and mutant UGT1A1*28 were 74.00% and 26.00%, respectively; The distribution frequencies of wild type and mutant UGT1A1*6 were 69.00% and 31%, respectively; There was no statistically significant difference between CYP2C19, UGT1A1*28 and UGT1A1*6 wild type and mutant patients in the age of onset, menstrual status, pathological type, clinical stage, estrogen receptor (ER) positive, progesterone receptor (PR) positive, hormone receptor (HR) positive ( χ2 values of CYP2C19 were 1.43, 0.38, 5.52, 0.61, 1.39, 0.01, 0.26, 1.16, χ 2 values of UGT1A1*28 were 0.63, 0.00, 2.88, 0.08, 1.94, 0.61, 2.74, 0.30, the χ2 values of UGT1A1*6 were 0.90, 0.10, 0.75, 0.09, 1.18, 0.11, 0.00, 0.37, P>0.05) ; The therapeutic effectiveness of CYP2C19, UGT1A1*28 and UGT1A1*6 wild type patients was higher than that of mutant type ( χ2=4.67, 4.86, 5.93, P<0.05) ; Logistic regression analysis showed that CYP2C19, UGT1A1*28 and UGT1A1*6 genotypes were independent risk factors for tamoxifen treatment effect ( β=0.465, 0.557, 0.568, P<0.05) . Conclusions:CYP2C19 and UGT1A1 gene polymorphisms are closely associated with tamoxifen treatment in breast cancer patients, and also lead to increased adverse reactions in patients. It is necessary to conduct CYP2C19 and UGT1A1 gene polymorphisms when tamoxifen is used in breast cancer patients to further optimize individualized drug therapy.

BACKGROUND: 3D-printing is widely used in regenerative medicine and is expected to achieve vaginal morphological restoration and true functional reconstruction. Mesenchymal stem cells-derived exosomes (MSCs-Exos) were applyed in the regeneration of various tissues. The current study aimed to explore the effctive of MSCs-Exos in vaginal reconstruction. METHODS: In this work, hydrogel was designed using decellularized extracellular matrix (dECM) and gelatin methacrylate (GelMA) and silk fibroin (SF). The biological scaffolds were constructed using desktop-stereolithography.The physicochemical properties of the hydrogels were evaluated; Some experiments have been conducted to evaluate exosomes’ effect of promotion vaginal reconstruction and to explore the mechanism in this process. RESULTS: It was observed that the sustained release property of exosomes in the hydrogel both in vitro and in vitro.The results revealed that 3D scaffold encapsulating exosomes expressed significant effects on the vascularization and musule regeneration of the regenerative vagina tissue. Also, MSCs-Exos strongly promoted vascularization in the vaginal reconstruction of rats, which may through the PI3K/AKT signaling pathway. CONCLUSION The use of exosome-hydrogel composites improved the epithelial regeneration of vaginal tissue, increased angiogenesis, and promoted smooth muscle tissue regeneration. 3D-printed, lumenal scaffold encapsulating exosomes might be used as a cell-free alternative treatment strategy for vaginal reconstruction.

BACKGROUND: Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a severe congenital disorder characterized by vaginal hypoplasia caused by dysplasia of the Müllerian duct. Patients with MRKH syndrome often require nonsurgical or surgical treatment to achieve satisfactory vaginal length and sexual outcomes. The extracellular matrix has been successfully used for vaginal reconstruction. METHODS: In this study, we developed a new biological material derived from porcine vagina (acellular vaginal matrix, AVM) to reconstruct the vagina in Bama miniature pigs. The histological characteristics and efficacy of acellularization of AVM were evaluated, and AVM was subsequently transplanted into Bama miniature pigs to reconstruct the vaginas. RESULTS: Macroscopic analysis showed that the neovaginas functioned well in all Bama miniature pigs with AVM implants. Histological analysis and electrophysiological evidence indicated that morphological and functional recovery was restored in normal vaginal tissues. Scanning electron microscopy showed that the neovaginas had mucosal folds characteristics of normal vagina. No significant differences were observed in the expression of CK14, HSP47, and a-actin between the neovaginas and normal vaginal tissues. However, the expression of estrogen receptor (ER) was significantly lower in the neovaginas than in normal vaginal tissues. In addition, AVM promoted the expression of b-catenin, c-Myc, and cyclin D1. These results suggest that AVM might promotes vaginal regeneration by activating the b-catenin/cMyc/cyclin D1 pathway. CONCLUSION This study reveals that porcine-derived AVM has potential application for vaginal regeneration.

Objective:To investigate the differences in understanding and diagnosis of polycystic ovary syn-drome(PCOS)among obstetricians and gynecologists with different clinical experiences,in order to promote com-munication and improve medical quality.Methods:This was a multi-center cross-sectional survey.Information on participants'basic information and their knowledge of PCOS comorbidities and treatment management was col-lected online.Physicians were divided into two groups according to their experience:experienced(>200 consulta-tions/year)and inexperienced(≤200 consultations/year).The differences in the diagnosis and treatment of PCOS among different groups were compared.Logistic regression analysis was used to explore other factors that might influence the diagnosis and treatment of PCOS.Results:1689 questionnaires were finally included,among which 95 were experienced and 1594 were inexperienced.①In the comparison of basic conditions,the proportion of experienced persons in tertiary hospitals and reproductive endocrinology specialties was higher than that of in-experienced persons(P<0.05);The percentage of experienced persons who predicted patients with comorbid insulin resistance(proportion>30%)and predicted comorbid overweight/obesity(proportion 30%-50%)was higher than that of less experienced persons(P<0.05).②There was no significant difference in the evaluation of PCOS and its complications among different groups(P>0.05).Logistic regression suggested that different expe-riencers did not significantly affect the assessment of androgens,OGTT and lipid testing(P>0.05).③There was no statistical significance in the choice of treatment for those with no fertility need(P>0.05).For those with fertili-ty needs,metformin and letrozole were more actively selected by experienced group than inexperience(P<0.05).In terms of weight loss,experienced participants were more active in using metformin(P<0.05)and were more likely to choose1.0 or1.5 g/d(P<0.05)than those with inexperience.Conclusions:There was no signifi-cant difference in PCOS assessment among participants with different experience,but in treatment,experienced participants were better able to take into account the multi-system abnormalities brought by PCOS,and at the same time,they give more comprehensive and accurate treatment opinions on patients with or without fertility needs.

BACKGROUND: As one of the most common endocrinal disorders for women at childbearing age, the diagnostic criteria of polycystic ovary syndrome (PCOS) have been defined differently among different international health organizations. Phenotypic heterogeneity of PCOS also brings about difficulties for its diagnosis and management assessment. Therefore, more efficient biomarkers representing the progression of PCOS are expected to be integrated into the monitoring of management process using metabolomic approaches. METHODS: In this prospective randomized controlled trial, 117 PCOS patients were enrolled from December 2016 to September 2017. Classical diagnostic parameters, blood glucose, and metabolome were measured in these patients before and at 2 months and 3 months of different medical interventions. The receiver operating characteristic (ROC) curves were built based on multivariate statistical analysis using data at baseline and 3 months' management, and combinational biomarkers with appreciable sensitivity and specificity were selected, which then validated with data collected at 2 months. RESULTS: A set of metabolites including glutamic acid, aspartic acid, 1-methylnicotinamide, acetylcarnitine, glycerophosphocholine, and oleamide were filtered out with high performance in representing the improvement through 3-month management of PCOS with high sensitivity and specificity in ROC analysis and validation with other two groups showed an appreciable area under the curve over 0.96. CONCLUSIONS: The six metabolites were representative of the remission of PCOS through medical intervention, making them a set of potential biomarkers for assessing the outcome of PCOS management. TRIAL REGISTRATION ClinicalTrials.gov, NCT03264638.
Biomarkers ; Female ; Humans ; Metabolomics ; Polycystic Ovary Syndrome/diagnosis* ; Prospective Studies ; ROC Curve

Background: Bovine papillomatosis is a type of proliferative tumor disease of skin and mucosae caused by bovine papillomavirus (BPV). As a transboundary and emerging disease in cattle, it poses a potential threat to the dairy industry. Objectives: The aim of this study is to detect and clarify the genetic diversity of BPV circulating in dairy cows in Xinjiang, China. Methods: 122 papilloma skin lesions from 8 intensive dairy farms located in different regions of Xinjiang, China were detected by polymerase chain reaction. The genetic evolution relationships of various types of BPVs were analyzed by examining this phylogenetic tree. Results: Ten genotypes of BPV (BPV1, BPV2, BPV3, BPV6, BPV7, BPV8, BPV10, BPV11, BPV13, and BPV14) were detected and identified in dairy cows. These were the first reported detections of BPV13 and BPV14 in Xinjiang, Mixed infections were detected, and there were geographical differences in the distribution of the BPV genotypes. Notably, the BPV infection rate among young cattle (< 1-year-old) developed from the same supply of frozen sperm was higher than that of the other young cows naturally raised under the same environmental conditions. Conclusions Genotyping based on the L1 gene of BPV showed that BPVs circulating in Xinjiang China displayed substantial genetic diversity. This study provided valuable data at the molecular epidemiology level, which is conducive to developing deep insights into the genetic diversity and pathogenic characteristics of BPVs in dairy cows.

Background: Bovine papillomatosis is a type of proliferative tumor disease of skin and mucosae caused by bovine papillomavirus (BPV). As a transboundary and emerging disease in cattle, it poses a potential threat to the dairy industry. Objectives: The aim of this study is to detect and clarify the genetic diversity of BPV circulating in dairy cows in Xinjiang, China. Methods: 122 papilloma skin lesions from 8 intensive dairy farms located in different regions of Xinjiang, China were detected by polymerase chain reaction. The genetic evolution relationships of various types of BPVs were analyzed by examining this phylogenetic tree. Results: Ten genotypes of BPV (BPV1, BPV2, BPV3, BPV6, BPV7, BPV8, BPV10, BPV11, BPV13, and BPV14) were detected and identified in dairy cows. These were the first reported detections of BPV13 and BPV14 in Xinjiang, Mixed infections were detected, and there were geographical differences in the distribution of the BPV genotypes. Notably, the BPV infection rate among young cattle (< 1-year-old) developed from the same supply of frozen sperm was higher than that of the other young cows naturally raised under the same environmental conditions. Conclusions Genotyping based on the L1 gene of BPV showed that BPVs circulating in Xinjiang China displayed substantial genetic diversity. This study provided valuable data at the molecular epidemiology level, which is conducive to developing deep insights into the genetic diversity and pathogenic characteristics of BPVs in dairy cows.

Objective:To explore the effect of Wnt/β-catenin signaling pathway on growth plate development of tibial growth plate in young chronic renal failure (CRF) rats.Methods:Four-week-old male SD rats were randomly divided into control group and CRF group ( n=20/per group). Control group was intragastric administration with distilled water, and CRF group was given adenine suspension (150 mg·kg -1·d -1). All the young rats were sacrificed after continuous gavages for 6 weeks. The full length of tibia was compared between the two groups. The width of tibia proximal growth plates was measured by micro-CT scanning, and the width of the growth plate was also measured in histological sections. Chondrocytes isolated from growth plate in two groups were cultured in vitro to P3 generation. Immunohistochemical staining was used to detect the expression of collagen Ⅱ, matrix metalloproteinase 13 (MMP-13) and β-catenin in chondrocytes. Western blotting was used to detect the protein expressions of collagen Ⅱ, MMP-13 and β-catenin. Results:Compared with the control group, the tibial length of rats in the CRF group was shorter [(27.32±5.81) mm vs (35.43±3.61) mm, t=5.226, P<0.001], the width of growth plate in micro-CT picture was more narrow [(0.72±0.22) mm vs (1.13±0.27) mm, t=5.096, P<0.001], and the relative width of the growth plate was also more narrow ( t=6.744, P<0.001) in histological sections. The results of immunohistochemistry and Western blotting showed the expressions of collagen Ⅱ in the CRF group decreased significantly ( t=8.212, P<0.001), MMP-13 ( t=13.091, P<0.001) and β-catenin ( t=7.534, P<0.001) increased significantly compared the control group in chondrocytes. Conclusion:The Wnt/β-catenin signaling pathway is highly expressed in the tibial growth plate of young rats with chronic renal failure, which leads to accelerated degeneration and differentiation of chondrocytes and a closure tendency of growth plate.