Exosomes derived from human embryonic mesenchymal stem cells promote osteochondral regeneration.

OBJECTIVE: Clinical and animal studies have demonstrated the efficacy of mesenchymal stem cell (MSC) therapies in cartilage repair. As the efficacy of many MSC-based therapies has been attributed to paracrine secretion, particularly extracellular vesicles/exosomes, we determine here if weekly intra-articular injections of human embryonic MSC-derived exosomes would repair and regenerate osteochondral defects in a rat model. METHODS: In this study, osteochondral defects were created on the trochlear grooves of both distal femurs in 12 adult rats. In each animal, one defect was treated with 100 µg exosomes and the contralateral defect treated with phosphate buffered saline (PBS). Intra-articular injections of exosomes or PBS were administered after surgery and thereafter weekly for a period of 12 weeks. Three unoperated age-matched animals served as native controls. Analyses were performed by histology, immunohistochemistry, and scoring at 6 and 12 weeks after surgery. RESULTS: Generally, exosome-treated defects showed enhanced gross appearance and improved histological scores than the contralateral PBS-treated defects. By 12 weeks, exosome-treated defects displayed complete restoration of cartilage and subchondral bone with characteristic features including a hyaline cartilage with good surface regularity, complete bonding to adjacent cartilage, and extracellular matrix deposition that closely resemble that of age-matched unoperated control. In contrast, there were only fibrous repair tissues found in the contralateral PBS-treated defects. CONCLUSION: This study demonstrates for the first time the efficacy of human embryonic MSC exosomes in cartilage repair, and the utility of MSC exosomes as a ready-to-use and 'cell-free' therapeutic alternative to cell-based MSC therapy.

Gene expression analysis of pretreatment biopsies predicts the pathological response of esophageal squamous cell carcinomas to neo-chemoradiotherapy.

BACKGROUND: Neoadjuvant chemoradiotherapy (neo-CRT) followed by surgery has been shown to improve esophageal squamous cell carcinoma (ESCC) patients' survival compared with surgery alone. However, the outcomes of CRT are heterogeneous, and no clinical or pathological method can currently predict CRT response. In this study, we aim to identify mRNA markers useful for ESCC CRT-response prediction. PATIENTS AND METHODS: Gene expression analyses were carried out on pretreated cancer biopsies from 28 ESCCs who received neo-CRT and surgery. Surgical specimens were assessed for pathological response to CRT. The differentially expressed genes identified by expression profiling were validated by real-time quantitative polymerase chain reaction (qPCR), and a classifying model was built from qPCR data using Fisher's linear discriminant analysis. The predictive power of this model was further assessed in a second set of 32 ESCCs. RESULTS: The profiling of the 28 ESCCs identified 10 differentially expressed genes with more than a twofold change between patients with pathological complete response (pCR) and less than pCR (

[Analysis of nystagmus and medical history of 121 patients positive with positional test].

Objective: To observe the characteristics of positional nystagmus and clinical profile of patients with positive positional test, and to explore its possible pathogenesis.Method: One hundred and twenty-one patients with positive positional test in the vestibular function examination were enrolled in the Peking University International Hospital from January to June in 2017. According to the 2017 BPPV guidelines, patients with test positive positional nystagmus were divided into two groups: definite BPPV and the controversial syndrome. Analyses of gender, age and characteristics of nystagmus, with or without recurrent dizziness, headache, and motion sickness were undertaken between the two groups, as well as response to the repositioning maneuver. Result: Of the total 121 cases, 49 cases were diagnosed as definite BPPV, accounting for 40.5%, 72 cases as controversial syndrome, accounting for 59.5%. The proportion of women in the two group was 76.2% and 78.9%, respectively. The average age of definite BPPV and the controversial syndrome was 51.2±16.8 and 51.3±15.7, respectively.There were significant differences in nystagmus duration, spontaneous nystagmus and nystagmus after headshaking between the two groups by chi square test(P<0.01). The mean intensity of horizontal and vertical nystagmus in posterior semicircular canal BPPV was(10.2±7.4) °/s and(36.6±17.5) °/respectively. And the mean intensity of nystagmus in the strong and weak side in horizontal semicircular canal BPPV was(40.8±25.1) °/s and(20.7±11.1) °/respectively. The intensity of horizontal and vertical nystagmus of the controversial syndrome group was(7.2±7.7) °/s and(7.2±4.3) °/s respectively. The incidence of headache in the controversial syndrome group was significantly higher than that in the BPPV group, P=0.013. According to the guidelines, patients were evaluated one day after the initial treatment. The cure rate and effective rate of the definite BPPV group was 75%(36/48) and 87.5%(42/48),and was 0 and 30.4% in the controversial syndrome group respectively. Conclusion: The patients in controversial syndrome group have a preponderance of exhibiting positive nystagmus during positional test. Nystagmus were usually of low velocity and sustained. Most of these cases presented spontaneous nystagmus and headshaking induced nystagmus, as well as headache and lacunar infarctions in history, and the response to the repositioning maneuver were often poor. It may be related to vestibular migraine and central nervous system. The diagnosis of BPPV must be prudent.Both characteristics of nystagmus and medical history should be carefully analyzed to avoid overdiagnosis.