Anti-senescence effect of acetyl dipeptide-1 cetyl ester on skin and its mechanism / 中国药科大学学报

@#Acetyl dipeptide-1 cetyl ester (AD-1) is a synthetic peptide composed of acetic acid and cetyl alcohol with arginine and tyrosine, which has certain anti-inflammatory and skin barrier enhancement effects, has been used in cosmetics for sensitive skin.Meanwhile, the ingredient has also been used in anti-aging cosmetics, but there is a lack of published scientific evidence on anti- senescence aspect.In this study, we investigated the related effects of AD-1 by evaluating its in vitro antioxidant and antiglycation efficacies.Furthermore, we established a photoaging model on primary rat dermal fibroblasts by repeated exposures to UVA irradiation.MTT assay was used to detect the effects of AD-1 on the cell viability.RT-qPCR was used to determine the effects of AD-1 on the mRNA levels of senescence-related p21, p53, MMPs, IL6, Col1, Col3 and autophagy-related p62, ATG5, ATG7.Western blot was used to detect the effects of AD-1 on the protein levels of p16, p21, p53, Col1, LC3B and p62.SA-β-gal was performed to indicate senescence level of the cell.MDC was performed to indicate autophagy level.Intracellular reactive oxygen species were monitored by fluorescent probes DCFH-DA.The results showed that AD-1 could reduce UVA-induced the cell damage and regulate the abnormal expression of mRNA levels. It alleviated the abnormal protein levels of p16, p21, p53, Col1, LC3B and p62 induced by UVA. These results suggested that AD-1 has not only antioxidant and antiglycation effects but also can activate autophagy to achieve anti-senescence effect.

Effects of interhemispheric multi-target intermittent theta burst stimulation on upper limb function in patients with stroke / 中国康复理论与实践

ObjectiveTo investigate the effect of intermittent theta burst stimulation (iTBS) of the multi-target cerebral cortex after stroke on functional recovery of the upper limb of the hemiplegic side. MethodsFrom November, 2019 to August, 2020, 40 stroke patients in Gansu Provine Hospital Rehabilitation Center were included and randomly divided into single-target stimulation group (n = 20) and multiple-target stimulation group (n = 20). Both groups underwent basic neurorehabilitation drug therapy and conventional rehabilitation exercises. The single-target stimulation group received repetitive transcranial magnetic stimulation (rTMS) (iTBS mode) only in the primary motor cortex (M1) of the affected side. The multi-target stimulation group received rTMS (iTBS mode) in the cerebellar cortex of the healthy brain and M1 of the affected side, once a day, six days a week, for four weeks. Before and after treatment, the scores of Fugl-Meyer Assessment-Upper Extremities (FMA-UE), Action Research Arm Test (ARAT) and modified Barthel Index (MBI), and the latency and amplitude of somatosensory-evoked potentials N20 were compared. ResultsNo serious adverse reaction occurred during treatment. After treatment, the scores of FMA-UE, MBI and ARAT, and the amplitude and latency of N20 improved in both groups (|t| > 3.478, |Z| > 2.243, P < 0.05); and the scores of FMA-UE and ARAT, and the amplitude of N20 were better in the multiple-target stimulation group than in the single-target stimulation group (t > 2.939, Z = -2.697, P < 0.01). ConclusionMulti-target stimulation is superior to single-target stimulation for improving upper limb motor function and N20 amplitude in the hemiplegics after stroke.

Research Status of Endothelialization of Poly （ε-caprolactone） Small-Caliber Vascular Graft Implanted in Animals / 医用生物力学

The most serious problem facing the implantation of vascular graft in the body is the formation of blood clots. In order to solve this problem, various attempts have been made by the scientific community for many years. However, endothelialization is the fundamental method to solve thrombosis and keep vascular graft open for a long time. Poly （ε-caprolactone） (PCL) has the advantages of biodegradability, low cost and good mechanical properties. In recent years, it has been widely used as tissue engineering scaffolds, drug deliverys and so on. This article mainly reviews the endothelialization of small-caliber vascular graft based on PCL after implanted in different animal models, as well as the endothelialization of the same animal model but under different implantation conditions, and trying to find the reasons why small-caliber vascular grafts are still not ideal in clinical applications at different angles such as the different animal models and the different way about endothelialization, and provide references for future animal model selection.

Effects of baicalin on depressive behavior and ERK/CREB protein in hippocampus of depression model mice / 中华行为医学与脑科学杂志

Objective:To explore the regulation effects of baicalin on the behavior as well as extracellular regulated protein kinase(ERK)and cAMP-response element binding protein(CREB) in chronic unpredictable mild stimulus(CUMS) model mice.Methods:Thirty ICR mice were randomly assigned to control(CON) group, model(CUMS) group, fluoxetine(FLU) group, baicalin high-dose(BA-H) group and baicalin low-dose(BA-L) group with 6 mice in each group.In addition to the CON group, the mice in the other four groups were modeled by CUMS method.The modeling was carried out for 42 days, and intragastric administration was carried out according to groups from the 21st day to the completion of modeling.After administration, the depression like behavior of mice was measured by sugar water preference test and water maze test.Western blot (WB) and reverse transcription polymerase chain reaction (RT-PCR) were used to detect the protein level and mRNA level of ERK and CREB in mouse hippocampus respectively.SPSS 21.0 was used for statistical analysis.After normal test and variance homogeneity test, one-way ANOVA was used for multi group comparison, and Tukey test was used for pairwise comparison.Results:Results from the sugar preference experiment showed that compared with CON group, the sugar preference rate of CUMS group was decreased ((82.88±2.00)%, (64.49±1.24)%, t=19.11, P<0.05). Compared with CUMS group, sugar preference rate in FLU group ((81.90±1.19) %), BA-H group (77.86±2.51)%) and BA-L group ((67.98±2.56)%) increased ( t=24.83, 11.68, 3.00, all P<0.05). The results of water maze test showed that compared with CON group, the number of crossing platform ((6.33±0.82), (1.83±0.75), t=9.93, P<0.05) and the target quadrant residence time ((46.83±4.78)s, (24.25±6.12)s, t=7.13, P<0.05) of mice in CUMS group were decreased, but the the escape latency was prolonged ((14.88±3.00) s, (70.70±4.77) s, t=24.26, P<0.05). Compared with CUMS group, the number of crossing platform ((5.00±0.89)times, (5.17±0.75)times and (3.33±0.82) times, t=6.64, 7.67, 3.31, all P<0.05), and the residence time in the target quadrant ((36.80±2.66) s, (36.82±5.62) s, (33.28±3.56) s, t=4.61, 3.71, 3.13, all P<0.05) in FLU group, BA-H group and BA-L group increased, but the escape latencies were shortened ((23.37±4.86) s, (34.83±4.72) s, (62.15±5.30) s, t=17.02, 13.10, 2.94, all P<0.05). WB results showed that compared with CON group, the expression of ERK protein ((1.00±0.15), (0.36±0.10), t= 6.26, P<0.05) and CREB protein((1.00±0.12), (0.29±0.03), t=10.32, P<0.05) in hippocampus of mice in CUMS group decreased.Compared with CUMS group, ERK protein in hippocampus of mice in FLU, BA-H and BA-L groups increased ((0.87±0.05), (0.77±0.08), (0.67±0.03), t=8.25, 5.7, 5.39, all P<0.05), and CREB protein in FLU, BA-H and BA-L groups were also increased ((0.90±0.12), (0.84±0.14), (0.62±0.04), t=8.94, 6.59, 12.25, all P<0.05). qPCR results showed that compared with CON group, ERK mRNA ((1.00±0.03), (0.41±0.10), t=9.78, P<0.05) and CREB mRNA ((1.00±0.08), (0.61±0.12), t=4.62, P<0.05) were decreased in CUMS group.Compared with CUMS group, ERK mRNA in hippocampus of mice in FLU, BA-H and BA-L groups were increased ((0.71±0.08), (0.69±0.03), (0.59±0.04), t=4.15, 4.65, 2.84, all P<0.05), CREB mRNA in FLU group and BA-H group were increased ((0.87±0.08), (0.86±0.07), t=3.14, 3.19, all P<0.05). Conclusion:BA can improve the depression-like behavior of CUMS model mice.The mechanism of action may be related to the regulation of ERK and CREB proteins.

Effects of High-Fat Diet on Rat Aortic Endothelial Cell Morphology and Stiffness / 医用生物力学

Objective To investigate the high-fat diet effect on morphology and stiffness of endothelial cells. Methods SD rats were randomly divided into high-fat diet group (AS group, n=3) and control group (CON group, n=3). Rat aortic endothelial cells were obtained from rat thoracic aorta by explant method. Cell morphology was observed under inverted microscopy. The mean fluorescent intensity of F-actin in two groups was calculated by immunofluorescence staining. Cell stiffness was measured by atomic force microscopy (AFM). Results The endothelial cells migrated from tissue plant on the 7th day and formed confluence after cultivation for 14 days. Endothelial cells were identified by factor Ⅷ immunofluorescence staining. Cells in AS group showed enhanced perimeter (P＜0.01), aspect ratio (P＜0.01), and area (P＞0.05), while less circularity (P＜0.01) compared with the cells in control group. The mean fluorescence intensity of F-actin in AS group was significantly higher than that in control group (P＜0.01). AFM showed that the cell stiffness of AS group was significantly higher than that of control group (P＜0.01). Conclusions High-fat diet would change the morphology and stiffness of endothelial cells, which might subsequently affect their normal function and become an important incentive to AS.

Analysis of therapeutic effect and prognosis of pancreatectomy, pancreatic duct drainage and combined procedures for pancreatic ductal stones / 中华胰腺病杂志

Objective To analyze the curative effect and prognosis of pancreatic ductal stone treated by pancreatectomy,pancreatic duct drainage or combined procedures.Methods The clinical data of 296 pancreatic ductal stone patients who received surgical treatment in First Affiliated Hospital of the Army Medical University between January 2008 and June 2017 were retrospectively analyzed.The cases were divided into pancreatectomy group (162 cases),pancreatic duct drainage group (104 cases) and combined procedures group (30 cases) according to their surgical procedures.The clinical characteristics and short-term and longterm outcomes of surgical treatment between the three groups were analyzed.Kaplan-Meier method was used to estimate the survival rate of no recurrence of pain after operation.Log-rank test and Cox-proportional hazard model were used to analyze the influencing factors on the recurrent pain free survival after surgery.Results The ratio of male patients was highest in pancreatectomy group,and the incidence of pancreatic exocrine insufficiency was highest in pancreatic duct drainage group.Of 296 patients,Ⅰ type pancreatic stone was most in pancreatectomy group and combined procedures group (80.2％,70.0％),and Ⅲ type pancreatic stone was most in pancreatic duct drainage group (46.2％).Medium size pancreatic stone was most in pancreatectomy group (52.5％),and medium and large size pancreatic stone was most in pancreatic duct drainage group (80.8％).Obvious pancreatic atrophy was most in pancreatic duct drainage group.Pancreatic head swelling,bile ductal dilation or compression,combined with pancreatic or surrounding organ complications were most in pancreatectomy,and all the differences were statistically significant (all P ＜ 0.05).In the short-term effect,the overall rate of pain relief was 99.3％,and there was no statistical difference among three groups.Pancreatic duct drainage group was superior to the other two groups in terms of operative time,bleeding volume,postoperative hospitalization days and postoperative complications (all P ＜0.05),but the total incidence of residual stones after operation in drainage group (64.8％) was higher than that in the other two groups,and the difference was statistically significant (all P ＜ 0.05).In the long-term effect,there were no significant differences in pain recurrence,stone recurrence reoperation,postoperative pancreatic function,body weight and quality of life recovery among the three groups.The 1-year,3-year and 5-year no recurrent pain after operation was 89.0％,79.2％ and 68.9％,respectively.Univariate and multivariate analysis showed that the course of CP ≥5 years(HR =2.113,95％ CI 1.160-3.848,P=0.014) and postoperative long-term alcohol consumption (HR =1.971,95％ CI 1.073-3.620,P =0.029) were independent risk factors affecting pain recurrence after surgery.Conclusions Surgery is still an important means for the treatment of pancreatic ductal stone.The short-term and long-term effect of pancreatectomy,pancreatic duct drainage and combined procedures for pancreatic ductal stones are definitely effective.However,none of the three methods can prevent the continued loss of pancreatic function in some patients.According to the preoperative clinical features,surgery strategy should be formulated individually,and the postoperative health guidance and follow-up should be emphasized,which can help to improve the prognosis of the patients with pancreatic ductal stones.

Impact of Cystic Fibrosis Transmembrane Conductance Regulator on Malignant Properties of KRAS Mutant Lung Adenocarcinoma A549 Cells / 中国肺癌杂志

BACKGROUND@#The incidence of lung cancer is gradually increased, and the cystic fibrosis transmembrane conductance regulator (CFTR) has recently demonstrated to have an implication in the deoncogenesis and malignant transformation of many types of cancers. The aim of this study is to investigate impacts of CFTR on the malignant features of lung adenocarcinoma A549 cells.@*METHODS@#The capacity of cell proliferation, migration, invasion and clonogenicity of non-small cell lung cancer A549 cells were detected by CCK8 cell proliferation assay, cell scratch assay, Transwell cell invasion assay and clone formation assay, respectively. Meanwhile, the effect of CFTR gene on the expression of cancer stem cell related transcriptional factors was also detected by immunoblotting (Western blot) assay.@*RESULTS@#An overexpression of CFTR gene in A549 cells significantly inhibited the malignant capacity of A549 cells, including potencies of cell proliferation, migration, invasion and colony formation; while knockdown of CFTR gene expression by RNA interference in A549 cells resulted in an opposite effect seen in above cells overexpressing CFTR gene. Mechanistically, immunoblotting assay further revealed that the ectopic expression of CFTR gene led an inhibitory expression of stem cell-related transcriptional factors SOX2 and OCT3/4, and cancer stem cell surface marker CD133 in A549 cells, while a knockdown of CFTR expression yielded a moderately increased expression of these gene. However, an alteration of CFTR gene expression had neither effect on the expression of putative lung cancer stem cell marker aldehyde dehydrogenase1 (ALDH1), nor the frequency of ALDH1A-positive cells in A549 cells, as ascertained by the immunoblotting assay and cytometry analysis, respectively.@*CONCLUSIONS@#The CFTR exhibited an inhibitory role in the malignancy of lung adenocarcinoma A549 cells, suggesting that it may be a novel potential target for lung cancer treatment. However, its functions in other lung adenocarcinoma cell lines and its underlying molecular mechanisms require further investigation.

Comparison of the application among intensity-modulated radiotherapy, 3D-conformal radiotherapy and conventional radiotherapy for locally advanced middle-low rectal cancer / 中华胃肠外科杂志

OBJECTIVE@#To compare the application among intensity-modulated radiotherapy (IMRT), three-dimensional conformal radiotherapy(3D-CRT) and conventional radiotherapy (CRT) for locally advanced middle-low rectal cancer.@*METHODS@#From January 2015 to December 2016, 93 locally advanced middle-low rectal cancer patients with clinical stage cT3N+M0 or cT4N0/+M0 who underwent preoperative concurrent chemoradiotherapy at Department of Colorectal Surgery, the Third Affiliated Hospital of Kunming Medical University and had complete data were enrolled in this retrospective cohort study. Patients were divided into IMRT group (17 cases), 3D-CRT group (28 cases) and CRT group (48 cases) according to different radiotherapy methods. The frequency and dose of CRT were 1 time/day, 5 times/week, for a total of 5 weeks, with a single dose of 2.0 Gy, the total dose was 50 Gy. Frequency and dose of 3D-CRT and IMRT were 1 time/day, 5 times/week, for a total of 23 to 28 times, with a single dose of 1.8 to 2.0 Gy, and a total dose of 45.0 to 50.4 Gy. The chemotherapy regimen was performed with capecitabine tablets at a dose of 825 mg/m twice a day for 5 days every week, at the same time during radiotherapy. The efficacy, chemotherapy adverse reactions and immune function of the three groups were compared.@*RESULTS@#There was no significant difference in the baseline data among the three groups (all P>0.05). The proportion of patients receiving permanent ostomy in the IMRT group and the 3D-CRT group was 29.4%(5/17) and 32.1%(9/28) respectively, which was lower than 58.3%(28/48) in CRT group, and the difference was statistically significant (χ²=7.982, P=0.030), while this proportion was not significantly different between IMRT and 3D-CRT group(χ²=0.037, P=0.848). The pathologic complete response(pCR) rate was 23.7%(22/93) in the whole study, and the pCR rate was 39.3%(11/28) in the 3D-CRT group, which was higher than that of CRT group and IMRT group [12.5%(6/48) and 29.4%(5/17)], and the difference was statistically significant (χ²=7.407, P=0.025), while there was no significant difference in pCR rate between CRT group and IMRT group (χ²=2.554, P=0.110). There was no adverse reaction of grade 3 or above in all three groups. No significant difference in the incidence of bone marrow suppression, abnormal liver and kidney function markers, digestive tract reaction or radiation dermatitis was found(all P>0.05). After receiving concurrent chemoradiotherapy, the proportion of CD3/CD4 cells in the IMRT group and the CRT group decreased compared with that before treatment(23.1±9.3 vs. 31.1±10.9, 27.4±10.7 vs. 33.6±7.2, respectively); the proportion of CD3/CD8 cells was up-regulated (36.1±15.2 vs. 24.8±10.9, 30.9±14.4 vs. 24.0±8.3,respectively), and the differences were statistically significant (both P0.05). After treatment, the proportion of CD4/CD8 cells in IMRT group decreased (0.8±0.6 vs. 1.6±1.0, t=3.838, P=0.003), while this proportion was not significantly different in CRT group and 3D-CRT group(all P>0.05).@*CONCLUSIONS@#IMRT and 3D-CRT can reduce the rate of permanent stoma. 3D-CRT can increase pCR rate. No obvious advantage is shown in IMRT as compared with 3D-CRT in the short-term efficacy. On the contrary, an immunosuppressive status may occur. Therefore, 3D-CRT is recommended as the best preoperative treatment strategy for patients with locally advanced middle-low rectal cancer, especially for those with immunosuppression status.

Efficacy analysis of transcatheter arterial chemoembolization combined with conventional percutaneous ethanol injection therapy in the treatment of 40 cases of primary liver cancer / 中国综合临床

Objective To study the curative effect of transcatheter arterial chemoembolization( TACE) combined with conventional percutaneous ethanol injection therapy ( PEIT) in the treatment for primary liver cancer?Methods Forty cases patients with primary liver cancer(the diameter was equal or more than 8 cm) who were treat in the Third Hospital of Qinhuangdao from January 2007 to May 2013 were selected,and randomly divided into treatment group(20 cases) and control group(20 cases)?The control group underwent TACE,the treatment group were given TACE combined with PEIT, the clinical effect of the two groups were observed?Results The effective rate of the treatment group was 80%,significantly higher than that of the control group( 50%) ,the difference was statistically significant( P=0?04)?During the follow?up of 3 years,there were 3 cases of portal vein tumor thrombus,5 cases of hepatic metastasis,1 case of upper gastrointestinal bleeding and 2 cases of liver failure in the control group;there were 1 case of liver metastasis,1 case of liver failure and death in the treatment group?Conclusion The test of the curative effect of patients with huge hepatocellular carcinoma after combination therapy with TACE and PEIT proved combination therapy can increase the curative effect, decrease impairment of liver funvtion?It was a palliation road to treat huge hepatocellular carcinoma.

An air-liquid interface model of human lung epithelium generated from bronchiolar epithelial cells proliferated using medium containing ROCK kinase inhibitor / 中国组织工程研究

BACKGROUND:Primary human lung epithelial cel s are difficult to be isolated and cultured in vitro, which is characterized as limited sources, low cel viability, slow proliferation capacity, and lacking of differentiation capability. OBJECTIVE:To establish an air-liquid interface model of lung epithelium by in vitro proliferation of human bronchiolar epithelial cel s, which is used for research on function of lung epithelial cel s. METHODS:Primary human bronchiolar epithelial cel s were isolated using Pronase and DNase I combined digestive methods, and then proliferated using medium containing ROCK kinase inhibitor. The proliferated cel s were used for establishment of the air-liquid interface epithelium model. Cel differentiation was identified using scanning electron microscope, phase contrast microscope and immunofluorescent staining. RESULTS AND CONCLUSION:The primary human bronchiolar epithelial cel s could be expanded successful y using medium containing ROCK kinase inhibitor, and the basal cel marker Cytokeratin14 was preferential y expressed in the proliferated cel population, indicating that these basal cel s might be the main subpopulation of human lung epithelial stem cel s. Subsequently, the proliferated cel s under the air-liquid interface could differentiate into ciliated cel s and non-ciliated column cel s. The results suggest that the proliferation and differentiation of human bronchiolar epithelial cel s were maintained in the presence of ROCK kinase inhibitor, and the air-liquid interface could promote the differentiation of human bronchiolar epithelial cel s.