Objective:Observing the effect of exosomes derived from hypoxic Bone marrow mesenchymal stem cells (BMSCs) on the function of chondrocytes, and exploring the role and mechanism of exosomal miR-196b-5p. Evaluating the application prospects of hypoxic BMSCs exosomes and miR-196b-5p for cartilage regeneration.Methods:Chondrocytes were cultured in the supernatant of BMSCs cultured under normoxia or hypoxia, respectively. The proliferation of chondrocytes was detected by CCK-8 assay and the expressions of Collagen type 2 (Col2), Col1, Aggrecan and SOX9 were detected by qPCR to evaluate the effect of hypoxic BMSCs paracrine on chondrocyte functions. Obtaining normoxic and hypoxic exosomes through ultracentrifugation, and testing their effects on the proliferation and anabolic-related genes of chondrocytes through CCK-8 assay and qPCR. Verifying the expression of miR-196b-5p in hypoxic exosomes based on exosomal miRNA array. Knocking out miR-196b-5p in hypoxic BMSCs, and detecting the effect of hypoxic exosomal miR-196b-5p on the functions of chondrocytes by loss-of-function assay. Predicting the downstream of miR-196b-5p through bioinformatics tools, and exploring the mechanism of hypoxic exosomal miR-196b-5p by gain-of-function assays. Hypoxic exosomes and miR-196b-5p-knockout hypoxic exosomes were loaded on silk fibroin hydrogel and subcutaneously into nude mice. After 4 weeks of culture, histological staining of saffron O, Masson and biochemical content of sGAG and collagen were performed to assess the application prospect of hypoxic exosomes and hypoxic exosomal miR-196b-5p on cartilage regeneration. Results:The results of CCK-8 assay and qPCR indicated that the supernatant of hypoxic BMSCs significantly promoted the proliferation of chondrocytes 1.20±0.07 and the expression of cartilage-related markers (Col2 2.95±0.17, Aggrecan 2.45±0.27, SOX9 2.92±0.29) compared to normoxic BMSCs (0.94±0.04, 1.89±0.09, 1.67±0.21, 1.76±0.16), the differences were statistically significant ( P<0.05). The result of CCK-8 assay showed that hypoxic exosomes (1.28±0.04) promoted the proliferation of chondrocytes compared to normoxic exosomes 1.05±0.06, the differences were statistically significant ( P<0.05). CCK-8 assay revealed that the down-regulation of miR-196b-5p in hypoxic exosomes 0.99±0.06 attenuated the proliferation of chondrocytes compared to control group 1.20±0.07, the differences were statistically significant ( P<0.05); the expression of Col2 0.56±0.04, Aggrecan 0.74±0.09, and SOX9 0.45±0.05 in chondrocytes was reduced in the miR-196b-5p knockdown group compared to the control group (1.00±0.09, 1.00±0.12, 1.00±0.07), the differences were statistically significant ( P<0.05). Co-transfection of pmirGLO-BACH1-WT reporter vector with miR-196b-5p mimics decreased the luciferase activity 0.73±0.06, the differences were statistically significant ( P<0.05). Co-transfection of pmirGLO-BACH1-MUT reporter vector with miR-196b-5p mimics showed no change in luciferase activity. BACH1 is the target of miR-196b-5p. Subcutaneous culture in nude mice showed that hypoxic exosomes significantly promoted the deposition of sGAG 383.2±21.54 and collagen 67.40±3.45, while reducing the expression of miR-196b-5p in hypoxic exosomes weakened the deposition of sGAG 258.4±19.50 and collagen 57.15±4.95, the differences were statistically significant ( P<0.05). Conclusion:Hypoxic exosomes promoted the functions of chondrocytes by inhibiting the expression of BACH1 through miR-196b-5p. Hypoxic exosomes can be applied in cartilage regeneration.

Objective:A new type of bio-ink and polycaprolactone (PCL) were used to construct an integrated osteochon-dral composite tissue block by multi-nozzle 3D bioprinter. And the repair results to osteochondral defects were evaluated.Methods:In freeze-drying group: Freeze-dried composite scaffold made by silk fibroin (SF) and β-tricalcium phosphate was used to repair osteochondral defects, as control. In the 3D printing group: PCL was used to printed a hollow multi-layer cylinder frame by 3D biological printer. Extracellular matrix, SF and bone marrow mesenchymal stem cells were used as chondral bio-ink. Then, chon-dral bio-ink was used to print tissue-engineered cartilage on top of PCL frame. Before implantation of cartilage defect, autogenous cancellous bone was filled in PCL frame, then the tissue-engineered osteochondral composite was used to repair osteochondral defects. In mosaic group: Autologous osteochondral transplantation was performed. The repair results of the above three groups were compared by histological score, biochemical analysis and biomechanical test to evaluate the effect of repairing rabbit cartilage defects.Results:The compression modulus of neo-cartilage in the 3D print group 2.56±0.30 MPa was close to that of the mosaic group 2.51±0.13 MPa ( P>0.05), and significantly higher than that of freeze-dried group 1.37±0.14 MPa ( F=11.058, P<0.05). The sGAG contents in the 3D print group 14.49±0.7 μg/mg was close to that of the mosaic group 14.98±0.81 μg/mg ( P>0.05), and significantly higher than that of freeze-dried group 8.72±0.73 μg/mg ( F=20.973, P<0.05). However, there was no significant difference in collagen content between the three groups ( P>0.05). The results of ICRS cartilage repair histology score showed that the scores of the 3D print group were close to those of the mosaic group in the matrix, cell distribution, cell viability and subchondral bone ( P>0.05), and were significantly higher than those of freeze-dried group in the surface and cartilage mineralization scores ( F=19.544, P<0.05). Conclusion:Using the new bio-ink to make bone cartilage composite scaffold by 3D bio printing can simplify the construction of tissue-engineered bone cartilage composite tissue in vitro, and can repair cartilage defects in vivo.

To strengthen the medical ethics education in the clinical practice stage in the department ot obstetrics and gynecology meets the requirements of the modern medical education under new situation.Aiming at the status quo of medical ethics education in China and abroad,this paper put forward specific recommendations in terms of the setting of teaching contents,the design of teaching approaches,the construction of teaching staff,as well as the evaluation of teaching achievements,and thus to enhance the understanding of medical students and interns to medical ethics and cultivate their practical capacity of analyzing and solving problems in clinical ethical dilemmas.

Objective To explore the feasibility of low concentration contrast medium and low-voltage combined with adaptive statistical iterative reconstruction(ASRI)technique in enhanced CT imaging of solitary pulmonary nodules. Methods A total of 40 patients with solitary pulmonary nodules who underwent routine exam-inations and were pathologically confirmed from February 2015 to February 2017 were collected and divided into conventional group(conventional dose,high osmolar contrast,using filtered back projection reconstruction)and low dose group(low voltage,low concentration isotonic contrast,iterative reconstruction). Results Subjective scoring of conventional group(3.97 ± 0.57)and low dose group(4.01 ± 0.54)indicated no statistical significance (P > 0.05). No significant difference was found regarding to reconstructed image quality,SNR and CNR in both two groups.The dose length product(DLP)and effective dose(ED)in low dose group were lower than those in the conventional group[(283.52 ± 11.50)mGy/cm vs(370.74 ± 29.56)mGy/cm;(3.65 ± 0.32)mSV vs(5.11±0.25) mSV],and the difference was statistically significant(P < 0.05). Conclusions Low concentration isotonic con-trast agent(iodixanol 270 mgI/L)and low voltage(100 kV)combined with ASIR technology could satisfy the clini-cal need in enhanced CT imaging of solitary pulmonary nodule.

BACKGROUND:Matrix metal oproteinase-13 is most active in the degradation of col agen type II in the extracel ular matrix of cartilage. Interleukin-1 (IL-1) is thought to be the inducer of matrix metal oproteinases, and participates in the degradation and degeneration of articular cartilage. OBJECTIVE:To study the influence of IL-1βon microRNA-27b (miR-27b) and matrix metal oproteinase-13 expression of chondrocytes in rats. METHODS:Chondrocytes isolated from seven male Wistar rats were cultured and divided into IL-1βstimulation group and control group. No stimulus was given in the control group;10μg/L of serum free medium was used to culture rat chondrocytes in the IL-1βstimulation group. Cel growth was observed at 0, 24, and 48 hours under an inverted microscope. miR-27b and matrix metal oproteinase-13 expression in the cultured chondrocytes were detected. RESULTS AND CONCLUSION:The relative expression of matrix metal oproteinase-13 in rat chondrocytes was gradual y increased when induced by IL-1βat 0, 24, and 48 hours (P<0.05). Expression of miR-27b and miR-31 in rat chondrocytes at 24 and 48 hours induced by IL-1βgradual y decreased (P<0.05);conversely, expression of MiR-26a, miR-26b, miR-23, and miR-204 gradual y increased (P<0.05). After 48 hours of IL-1βinduction, expression of miR-27b was the lowest in rat chondrocytes (P<0.05). These findings suggest that IL-1βinhibits miR-27b expression, strengthens the expression of matrix metal oproteinase-13, and damages chondrocytes, contributing to both the onset and progression of osteoarthritis.

BACKGROUND:Autologous tissue-engineered bone marrow mesenchymal stem cel s (BMSCs) transplantation is one of the most common methods of treating early osteonecrosis of femoral head, but now there is stil no any special-purpose grafter available in the market. Such surgical transplantation is a laborious, time-consuming and tedious process, which goes against its clinical promotion. OBJECTIVE:To develop a supporting, efficient, special-purpose grafter, to solve the difficulty in stem cel s transplantation during core decompression of femoral head. METHODS:CAD software was used to perform solid modeling for this special-purpose grafter and print them by three-dimensional (3D) fast printing technology. The performance of this special-purpose grafter was tested by femoral head core decompression combined with BMSCs transplantation. It was compared with traditional surgical instrument in terms of duration of operation, intraoperative blood loss, visual analogue scale (VAS) of stem cel/biological fiber col agen complex omission amount and doctor’s satisfaction score. RESULTS AND CONCLUSION:(1) A kind of special-purpose grafter was developed by 3D printing technology rapidly. (2) Compared with the control group, duration of operation, intraoperative blood loss, VAS scores and doctor’s satisfaction scores were significantly improved in the trial group (P<0.05). (3) CAD software combined with 3D printing technology is a highly efficient means for front-line clinicians to perform independent development. The research and development of this special-purpose grafter provides a perfect solution to the laborious, time-consuming and tedious process of cel/biological col agen fiber transplantation.

Objective Negative pressure aspirator clogging ( OSAC) frequently occurs in orthopedic surgery .This study was to investigate the frequency , location , and mechanisms of OSAC in China by analysis of the current status and clinical observation of OSAC so as to provide evidence for the solution of the problem . Methods Using the two-stage random sampling method , we conduc-ted a questionnaire survey on OSAC among 738 clinical orthopedists during the 16th and 17th Chinese Orthopedic Association Confer-ences.Totally, 160 out 1200 orthopedic surgeries were randomly selected in the time order of operation , including 38 cases of total hip arthroplasty ( THA) , 39 cases of total knee arthroplasty ( TKA) , 43 cases of extremity and spinal fractures surgery , and 40 cases of other orthopedic surgeries .We also obtained the satisfaction scores with the existing aspirators from related medical professionals . Results Among the 738 respondents included into the analysis , 706 (95.7%) thought that OSAC often occurred during surgery , 631 (85.5%) considered THA to be the leading cause of OSAC , and 714 (96.7%) regarded the tip and hose joint of the aspirator as the common causes . The mean satisfaction score with the existing aspirators was 7.62 ±0.74.Clinical observation showed the mean frequency of OSAC to be 2.55 ±1.62 in THA, 1.95 ±1.33 in TKA, 1.52 ±1.18 in extremity and spinal fracture surgeries , and 0.95 ± 0.68 in other orthopedic surgeries , and the satisfaction score to be 7.36 ±0.84. Conclusion OSAC has a high incidence rate during orthopedic surgeries in China , thus affecting orthopedic surgery and reducing orthopedists'satisfaction with the aspirators . The current negative pressure aspirator system demands prompt improvement .

Objective To investigate toe-brachial index ( TBI) in the diagnosis of peripheral artery disease ( PAD) and its risk factors in the patients with type 2 diabetes.Methods TBI was examined in the 238 patients with type 2 diabetes.The patients were divided into the group with low TBI ( TBI≤0.7 ) and the group with normal ABI ( TBI>0.7 ) .The two groups were compared for clinical parameters.Results Thirty two patients (13.4%)with abnormal ABI (TBI≤0.7) showed older age [(63.8 ±9.9) yrs vs (54.9 ±10.8) yrs, P =0.000] , lower diastolic blood pressure [(70.5 ±6.9) mmHg vs (74.9 ±9.1) mmHg, P =0.003], more frequency of hypertension (56.3%vs 38.3%, P =0.043), coronary artery heart disease (28.7%vs 10.7%, P =0.020) and cere-bral vascular disease (15.6%vs 4.4%, P =0.025).Step-wise analysis screened that age and diastolic blood pressure were the inde-pendent risk factors for TBI .Conclusions Aging and hypertension were the risk factors in the patients with abnormal TBI in type 2 di-abetes.TBI was an easy and economical method for diagnosing PAD in patients with type 2 diabetes.

Resveratrol is a kind of polyphenolic compounds, and widely exists in plants.It can be provided with comprehensive physiological and pharmacological effects. In this paper, the authors reviewed the effect of resveratrol on myocardial ischemia-reperfusion injury, the effective treatment of atherosclerotic diseases and coronary heart disease, and discuss the protective effect and the mechanism of resveratrol on cardiovascular disease through the effect of the electrophysiology and the accommodation of the blood vessel.

OBJECTIVETo define the determinants of perioperative death and complications after cardiac valve replacement in 702 patients.

METHODSClinical data of the patients after cardiac valve replacement were analyzed retrospectively.

RESULTSPerioperative mortality and morbidity correlated significantly with some of the perioperative variables, such as higher NYHA functional class (III or IV), large left ventricular end-diastolic diameter (>/= 70 mm), C/T >/= 0.70, prolonged aortic cross-clamping time and cardiopulmonary bypass time, unsatisfactory myocardial protection.

CONCLUSIONSPerioperative mortality and morbidity correlate significantly with some of perioperative variables, such as higher NYHA functional class, unsatisfactory myocardial protection, inappropriate surgical procedure, improper therapy of some complications after cardiac valve replacement. To avoid the occurrence of these independent predictors or to correct them timely might effectively decrease the perioperative mortality and morbidity after cardiac valve replacement.

Adolescent ; Adult ; Aged ; Cause of Death ; Child ; Female ; Heart Valve Diseases ; mortality ; surgery ; Heart Valve Prosthesis ; adverse effects ; Humans ; Intraoperative Complications ; mortality ; Male ; Middle Aged ; Mortality ; Postoperative Complications ; mortality