Extracellular Vesicles from Adipose-Derived Stem Cells Promote Diabetic Wound Healing via the PI3K-AKT-mTOR-HIF-1a Signaling Pathway

BACKGROUND@#Impaired potential of hypoxia-mediated angiogenesis lead poor healing of diabetic wounds. Previous studies have shown that extracellular vesicles from adipose derived stem cells (ADSC-EVs) accelerate wound healing with unelucidated mechanism. However, it is not yet clear about the underlying mechanism of ADSC-EVs in regulating the hypoxia-related PI3K/AKT/mTOR signaling pathway of vascular endothelial cells in diabetic wounds. Therefore, in this study, human derived ADSC-EVs (hADSC-EVs) isolated from adipose tissue were co-cultured with advanced glycosylation end product (AGE) treated human umbilical vein endothelial cells (HUVECs) in vitro and local injected into the wounds of diabetic rats. @*METHODS@#In vitro, the therapeutic potential of hADSC-EVs on AGE-treated HUVECs was evaluated by cell counting kit-8, scratching, and tube formation assay. Subsequently, the effects of hADSC-EVs on the PI3K/AKT/mTOR/HIF-1a signaling pathway were also assayed by qRT-PCR and western blot. In vivo, the effect of hADSC-EVs on diabetic wound healing in rats were also assayed by closure kinetics, Masson staining and HIF-1α-CD31 immunofluorescence. @*RESULTS@#hADSC-EVs were spherical in shape with an average particle size of 198.1 ± 91.5 nm, and were positive for CD63, CD9 and TSG101. hADSC-EVs promoted the expression of PI3K-AKT-mTOR-HIF-1a signaling pathway of AGEs treated HUVECs with improved the potential of proliferation, migration and tube formation, and improve the healing and angiogenesis of diabetic wound in rats. However, the effect of hADSC-EVs described above can be blocked by PI3K-AKT inhibitor both in vitro and vivo. @*CONCLUSION@#Our findings indicated that hADSC-EVs accolated the healing of diabetic wounds by promoting HIF-1α-mediated angiogenesis in the PI3K-AKT-mTOR depend manner.

Classification of mammography images with the methods of segmentation and multiple features fusion / 国际生物医学工程杂志

Objective:To combine automatic image segmentation technology and machine learning methods to accurately classify and recognize mammography images.Methods:Taking mammography images with clustered pleomorphic calcification as the research object, which were in BI-RADS4 class from the Digital Mammogram Database (DDSM). The region of interest (ROI) of the images was automatically segmented. The characteristic features extracted by wavelet transform, Gabor filter and gray level co-occurrence matrix method were fused. The fused feature parameters were screened based on sensitivity analysis. Using ensemble learning method, the polynomial kernel SVM, random forest and logistic regression classifiers were integrated to form a classifier for automatic classification of mammography images. The ensemble learning method was soft voting integration.Results:The proposed ensemble classifier can efficiently recognize and classify mammography images, and its classification sensitivity, specificity and accuracy on the training set were 99.1%, 99.6% and 99.3%, respectively.Conclusions:The proposed mammography image processing, classification and recognition method can provide assistant detection basis for doctors' clinical judgment, and provide a technical basis for subdividing BI-RADS4 class images.

Clinical evaluation of microorganisms identification from midstream urine by MALDI-TOF MS with different sample enrichment methods / 中华检验医学杂志

Objective To evaluate the clinical effect of direct identification of microorganisms from the midstream urine by MALDI-TOF MS combined with separation gel tube and differential centrifugation. Methods A total of 2150 samples of midstream urine were collected from the outpatient and inpatients in Huadong Hospital affiliated to Fudan University from May 2017 to April 2018, including 934 males and 1216 females with an age of (72.0 ± 17.5) years. After preliminary quantification by microscopic examination, samples with a bacterial acount of ≥ 105cfu/ml were treated with two kinds of pretreatment methods to enrich the bacteria for directly identification by MS. Based on the results of quantitative urine culture and MS identification,the coincidence rates of two kinds of pretreatment methods combined with MS were analyzed. All statistical analyses were performed using Stata/SE 14.0, differences between the groups were compared by Pearson Chi-square tests. Results 464 out of 2150 midstream urine samples (21.6％) had a bacterial count ≥ 105cfu/ml after microscopic examination. In traditional culture combined with MALDI-TOF MS, 436(94.0％)cases were single species, 28(6.0％)cases were double species. Among single species of bacteria samples infection, the gram-negative bacteria accounted for 78.9％(344/436),the Gram-positive bacteria accounted for 15.8％(69/436),and the fungus accounted for 5.3％(23/436). In two methods that the separation gel tube combined MALDI-TOF MS and the differential centrifugation combined MALDI-TOF MS, the gram-negative bacteria coincidence rates were 92.4％(318/344)and 89.0％(306/344) respectively, the Gram-positive bacteria coincidence rates were 68.1％(47/69)and 62.3％(43/69) respectively,and the fungi coincidence rates were 56.5％(13/23) and 34.8％(8/23)respectively. Meanwhile,the double bacteria infection coincidence rates were 64.3％(18/28)and 60.7％(17/28). Conclusions The separation gel tube combined MALDI-TOF MS and the differential centrifugation combined MALDI-TOF MS identify directly the gram-negative bacteria in the midstream urine samples with high detection rate and accuracy,and they are rapid and simple pretreatment method,suitable for rapid screening of midstream urine.

Inactivation of TFEB and NF-B by marchantin M alleviates the chemotherapy-driven pro-tumorigenic senescent secretion

It is critical to regulate the senescence-associated secretory phenotype (SASP) due to its effect on promoting malignant phenotypes and limiting the efficiency of cancer therapy. In this study, we demonstrated that marchantin M (Mar-M, a naturally occurring bisbibenzyl) suppressed pro-inflammatory SASP components which were elevated in chemotherapy-resistant cells. Mar-M treatment attenuated the pro-tumorigenic effects of SASP and enhanced survival in drug-resistant mouse models. No toxicity was detected on normal fibroblast cells or in animals following this treatment. Inactivation of transcription factor EB (TFEB) and nuclear factor-B (NF-B) by Mar-M significantly accounted for its suppression on the components of SASP. Furthermore, inhibition of SASP by Mar-M contributed to a synergistic effect during co-treatment with doxorubicin to lower toxicity and enhance antitumor efficacy. Thus, chemotherapy-driven pro-inflammatory activity, seen to contribute to drug-resistance, is an important target for Mar-M. By decreasing SASP, Mar-M may be a potential approach to overcome tumor malignancy.

Inter-laboratory comparisons of measuring instruments of microwave radiation in the workplace / 中国职业医学

OBJECTIVE: To evaluate the feasibility of the inter-laboratory comparison of microwave radiation measuring instruments which uses cellphone signal shielding device as standard source,and to establish inter-laboratory comparison method of microwave radiation.METHODS: The typical sampling method has been used by selecting twenty-one measuring instruments of microwave radiation from 21 occupational hygiene technical service organizations as study subjects.A cellphone signal shielding device was applied as standard source.Measurement points were measured by surveyors at a distance of 1.0 and 1.5 meter to the standard source,and the measurement results were analyzed by four robust technology and z-score evaluation method.RESULTS: Stability test showed that there was no statistical difference among the power density of standard source which were measurement at three diffluent time [(26.10 ± 0.94) vs(25.78 ± 0.27) vs(25.83 ±0.47) μW/cm~2,P>0.05].The standard source stability can also satisfy the requirement of inter-laboratory comparison.Among the 21 selected equipments,one of the 21 measuring instruments was not calibrated,one calibration certificate of the instruments was expired,and one calibration result of the instruments was unqualified.The z score of inter-laboratory(z_B) of 21 measuring instruments ranged from-1.27 to 4.85,while z score of within-laboratory(z_w) ranged from-1.42 to 2.18.One | z_B| of the instruments was above 3.00,while | z_W| was above 2.00.Comprehensive evaluation of the above results showed that only one instrument was unqualified.CONCLUSION: It is feasible that a cellphone signal shielding device could be applied as standard source.The method developed in this study can be used to understand the performance of microwave radiation instruments.

Synthesis, photostability and bioactivity of 2,3-cyclopropanated abscisic acid.

The plant hormone abscisic acid (ABA) plays a central role in the regulation of plant development and adaptation to environmental stress. The isomerization of ABA to the biologically inactive 2E-isomer by light considerably limits its applications in agricultural fields. To overcome this shortcoming, an ABA analogue, cis-2,3-cyclopropanated ABA, was synthesized, and its photostability and biological activities were investigated. This compound showed high photostability under UV light exposure, which was 4-fold higher than that of (±)-ABA. cis-2,3-cyclopropanated ABA exhibited high ABA-like activity, including the ability to effectively inhibit seed germination, seedling growth and stomatal movements of Arabidopsis. In some cases, its bioactivity approaches that of (±)-ABA. trans-2,3-cyclopropanated abscisic acid was also prepared, an isomer that was more photostable but which showed weak ABA-like activity.

Clinical study on Du moxibustion for stable phase of chronic obstructive pulmonary disease / 国际中医中药杂志

Objective To investigate the Du moxibustion therapy in the treatment of chronic obstructive pulmonary disease (Chronic obstructive pulmonary disease,COPD)at stable phase.Methods 60 cases of lung COPD patients in stable stage who received treatment from January to December 2010 in Taihe Hospital of Traditional Chinese Medicine outpatient were randomly divided into two groups in,according to the case of tail number,with 30 patients in each.The control group was taken oral doxofylline tablets,0.2 g/time,2 time/d and ambroxol hydrochloride,30 mg/time,3 time/d.The treatment group was treated with Du moxibustion two times on the basis of the control group.One year follow-up and pulmonary function and BODE index assessment were performed in each group.Results ① the pulmonary function of the treatment group after the treatment (65.58±7.90) ％ was significantly improved than the same group before the treatment (53.20± 7.37) ％ (P＜0.05),and had significant difference compared with the control group after the treatment (57.53 ± 7.22)％ (P＜0.05).The recurrence rate was significantly different in the treatment group (1.79±0.32) and the control group (2.09±0.38) (P＜0.05).② BMI,MMRC,6MWD,BODE index,shortness of breath,wheezing,anorexia was significantly improved after the treatment in the treatment group [after treatment were (21.98 ± 1.32)kg/m2,(2.09±0.37)％,(350.68±88.70),(3.82±2.18) meters,(0.38±0.27),(0.32±0.25)％,(0.35±0.27) respectively; before treatment were (18.21±2.49)kg/m2,(2.50±0.43)％,(324.88±70.92),(4.66±1.40) meters,(1.49±0.62) ％,(1.42±0.56)％,(1.77±0.35),P＜0.01 respecitively].Compared with the control treatment after the treatment [(18.20 ± 1.79) kg/m2,(2.36 ± 0.64) ％,(320.03 ± 68.53),(4.43 ±1.62) meters,(1.22± 0.71),(1.28±0.67)％,(1.73±0.24) respectively] (P＞0.01),the difference was statistically significant(P＜0.01).Conclusion Du moxibustion therapy was effective in treating chronic obstructive pulmonary diseases in stable phase.

Value of regular and dual-time-point FDG PET/CT imaging in detecting recurrence and metastasis after a curative esophagectomy in esophageal carcinoma / 中华放射肿瘤学杂志

Objective To evaluate the clinical value of regular and dual-time-point 18-fluorodeoxyglucose positron emission tomography-CT(FDG PET/CT)imaging for recurrence and metastasis in esophageal carcinoma(EC)after curative esophagectomy. Methods A retrospective study was done on 48 patients received curative esophagectomy, who underwent FDG PET/CT scans to detect doubtful recurrent or metastatic lesions. The diagnostic accuracy of FDG PET-CT was assessed with the help of pathological findings as well as clinical or follow-up data. Using Fisher's Exact Test from SPSS 11.5 to analyze the data.Results Of the 48 patients, after a median follow-up of 21.5 months, 61 sites of local and regional recurrence or metastasis were finally confirmed in 34 patients. The sensitivity, specificity and accuracy of regular FDG PET/CT imaging in detecting recurrence of all sites were 93.44%, 74.29% and 86.46%respectively. The specificity and accuracy of local recurrence and regional metastasis were 57.14% ,78.95% and 77.78% ,84.62%, respectively. The sensitivity, specificity and accuracy of dual-time-point FDG PET/ CT imaging in detecting local and regional recurrence(96.97% ,96.00% and 96.55%)were higher than those of regular FDG PET/CT(90.90%, 72.00% and 82.76%)and there were significant differences of specificity and accuracy(P = 0.049, P = 0.029). Conclusions Regular FDG PET/CT imaging is highly effective in detecting recurrence and metastasis in EC patients after curative esophagectomy despite the low specificity and accuracy. Dual-time-point FDG PET/CT imaging can elevate the specificity and accuracy.

Expression and clinical significance of PTEN in non-small cell lung cancer / 中国癌症杂志

Purpose:To study the expression and clinical significance of PTEN in non-small cell lung cancer. Methods:Immunohistochemical staining was used to determine the expression of PTEN in 10 cases of normal lung issues and 56 cases of non-small cell lung cancer. Results:The positive incidences of PTEN expression in NSCLC was 59% while positive expression was found in all normal lung issues. The expression of PTEN was correlated to degree of differention of cancer, lymph node metastasis and clinical stages. The PTEN negative group was seen to have the worst survival rate among all groups. Conclusions:The results suggest that PTEN gene plays an important role in carcinogenesis and progress of NSCLC. Expression of PTEN may be valuable in prognosis assessment of NSCLC.