BACKGROUND:Myocardial patches are used as an effective way to repair damaged myocardium,and there is controversy over which cells to use to make myocardial patches and how to maximize the therapeutic effect of myocardial patches in vivo. OBJECTIVE:To find out the best way to make myocardial patches by overviewing the cellular sources of myocardial patches and strategies for perfecting them. METHODS:The first author searched PubMed and Web of Science databases by using"cell sheet,cell patch,cardiomyocytes,cardiac progenitor cells,fibroblasts,embryonic stem cell,mesenchymal stem cells"as English search terms,and searched CNKI and Wanfang databases by using"myocardial patch,biological 3D printing,myocardial"as Chinese search terms.After enrollment screening,94 articles were ultimately included in the result analysis. RESULTS AND CONCLUSION:(1)The cellular sources of myocardial patches are mainly divided into three categories:somatic cells,monoenergetic stem cells,and pluripotent stem cells,respectively.There are rich sources of cells for myocardial patches,but not all of them are suitable for making myocardial patches,e.g.,myocardial patches made from fibroblasts and skeletal myoblasts carry a risk of arrhythmogenicity,and mesenchymal stem cells have a short in vivo duration of action and ethical concerns.With the discovery of induced multifunctional stem cells,a reliable source of cells for making myocardial patches is available.(2)There are two methods of making myocardial patches.One is using cell sheet technology.The other is using biological 3D printing technology.Cell sheet technology can preserve the extracellular matrix components intact and can maximally mimic the cell growth ring in vivo.However,it is still difficult to obtain myocardial patches with three-dimensional structure by cell sheet technology.Biologicasl 3D printing technology,however,can be used to obtain myocardial patches with three-dimensional structures through computerized personalized design.(3)The strategies for perfecting myocardial patches mainly include:making myocardial patches after co-cultivation of multiple cells,improving the ink formulation and scaffold composition in biological 3D printing technology,improving the therapeutic effect of myocardial patches,suppressing immune rejection after transplantation,and perfecting the differentiation and cultivation protocols of stem cells.(4)There is no optimal cell source or method for making myocardial patches,and myocardial patches obtained from a particular cell or technique alone often do not achieve the desired therapeutic effect.Therefore,researchers need to choose the appropriate strategy for making myocardial patches based on the desired therapeutic effect before making them.

BACKGROUND:The anterior cruciate ligament has unique nonlinear mechanical properties under a complex physiological loading environment.Elastin is an important contributor to the mechanical properties of the anterior cruciate ligament,but its mechanical response to the anterior cruciate ligament under axial tension is not clear. OBJECTIVE:To quantitatively analyze the effect of elastin on the tensile mechanical response of the anterior cruciate ligament. METHODS:Elastase solution and control buffer were prepared.The porcine anterior cruciate ligament samples were prepared into small-size samples and randomly soaked in 0,0.1,1.0,2.0,5.0,and 10.0 U/mL elastase solution for 6 hours,and other small samples of the same size were soaked in 2 U/mL elastase solution for 0,1,3,6,9,and 12 hours.To determine suitable soaking conditions for elastin-targeted enzymes and verify the digestive effect,histological staining was used to compare the effects of enzyme treatment on tissue structure and composition.The ligament samples were randomly divided into elastase-treated group and PBS group,and immersed in 2 U/mL elastase solution and PBS buffer for 6 hours,respectively.A mechanical tensile test was performed before and after immersion. RESULTS AND CONCLUSION:(1)The biochemical results showed that being treated in 2 U/mL elastase solution for 6 hours could reduce the elastin content by 31.1%,and had no significant effect on other mechanical-related components in the tissue.(2)The histological results showed that elastase was able to penetrate the tissue,and the loose degree of tissue increased after treatment.(3)In the mechanical results before and after treatment,the mechanical properties of the PBS group decreased significantly,only the low-tension elastic modulus increased significantly and the initial length increased significantly in the elastase-treated group.(4)The intergroup comparison results showed that there was no significant difference between the two groups in pre-treatment,but the low-tension elastic modulus,initial slopes,saturated slopes,and initial length of the elastase-treated group after treatment were significantly higher than those in the PBS group.(5)These results suggest that elastin degradation significantly affects the biomechanical properties of the anterior cruciate ligament and further complements our understanding of the structure-function relationship of the anterior cruciate ligament.

This paper summarized professor WANG Shouchuan's experience in differentiating and treating children epistaxis from the perspective of "four excess and three deficiency". It is believed that the pathogenesis of children epistaxis is concluded as "four excess and three deficiency"， of which the four excess syndromes are exuberant heat in the lung channel， intense stomach fire， heart fire hyperactivity， and liver fire flaming upward， while the three deficiency syndromes include qi， yin and yang deficiency. Seven methods for treating children epistaxis are summarized. For exuberant heat in the lung channel syndrome， it is recommended to clear lung and direct qi downward， using self-made Xiebai Zhiniu Decoction （泻白止衄汤）. For intense stomach fire syndrome， the method of clearing stomach and draining fire can be used with self-made Qingwei Zhiniu Decoction （清胃止衄汤）. In terms of heart fire hyperactivity syndrome， it is better to clear heart and drain fire， using self-made Daochi Zhiniu Decoction （导赤止衄汤）. For liver fire flaming upward syndrome， it is advised to clear liver and drain fire， using self-made Yimu Zhiniu Decoction （抑木止衄汤）. In terms of qi deficiency syndrome， the method of fortifying spleen and boosting qi and containing blood should be used with self-made Futu Zhiniu Decoction （扶土止衄汤）. If there is yin deficiency syndrome， it is advised to supplement kidney， enrich yin and clear heat， using self-made Zishui Zhiniu Decoction （滋水止衄汤）. If there is yang deficiency syndrome， the method of boosting qi， warming yang and nourishing blood can be used， using self-made Wenpi Zhiniu Decoction （温脾止衄汤）.

Humans ; Consensus ; Pancreatic Neoplasms/therapy* ; Neuroendocrine Tumors/therapy*

Objective:To analyze the value of peritumoral vascular invasion (PVI) on the prognosis of patients with osteosarcoma.Methods:A total of 232 patients with primary osteosarcoma from 2007 to 2016 were retrospectively analyzed, including 142 males and 90 females. The average age was 17.9±8.2 years (range, 3-39 years). There were 22 positive and 210 negative cases of PVI, 94 deaths and 138 survivals. Univariate survival analysis (Log-rank test and univariate Cox regression) was used to evaluate the effects of age, gender, PVI status, tumor location, surgical method, sensitivity to chemotherapy, and chemotherapy regimen on the prognosis of osteosarcoma. The indicators with statistically significant differences were included in the multivariate Cox regression model to finally determine the risk factors affecting the prognosis of osteosarcoma. The relationship between PVI status and 5-year survival and the incidence of recurrence or metastasis was evaluated using the Kaplan-Meier method.Results:All patients were followed up for 7.6±4.5 years (range, 0.1-15 years). The differences in sensitivity to chemotherapy (χ 2=9.52, P=0.002), choice of chemotherapy regimen (χ 2=8.87, P=0.012), choice of surgical modality (χ 2=13.50, P<0.001), tumor metastasis rate (χ 2=8.51, P=0.004) and mortality rate (χ 2=5.39, P= 0.020) of PVI positive group and PVI negative group had statistically significant differences. Univariate survival analysis was performed on 232 patients with osteosarcoma (gender, age, PVI status, site of tumor development, surgical modality, sensitivity to chemotherapy, and chemotherapy regimen). Indicators with statistically significant differences were included in a multifactorial Cox regression model. The results showed PVI positive [5-year survival rate: HR=2.02, 95% CI (1.61, 2.79), P=0.010; 5-year recurrence or metastasis rate: HR=2.25, 95% CI (1.55, 3.14), P<0.001], surgical procedure as amputation [5-year survival rate: HR=1.22, 95% CI (0.94, 1.78), P=0.037; 5-year recurrence or metastasis rate: HR=1.58, 95% CI (1.11, 2.23), P=0.026] and poor sensitivity to chemotherapy [5-year survival rate: HR=2.71, 95% CI (1.84, 3.98), P=0.001; 5-year recurrence or metastasis rate: HR=2.52, 95% CI (1.88, 3.45), P<0.001] was associated with poor prognosis. Kaplan-Meier curve showed that the 5-year survival rate of PVI positive group was 34%, which was lower than 68% of PVI negative group. The 5-year recurrence or metastasis rate was 72% in the PVI negative group, which was significantly higher than 38% in the PVI negative group ( P<0.05). Conclusion:The 5-year survival rate of PVI positive group was lower than that of PVI negative group, and the 5-year recurrence or metastasis rate was higher than that of PVI negative group. The presence of microvascular angiosarcoma plugs infiltrating the peritumoral tissue in surgical specimens of osteosarcoma after neoadjuvant chemotherapy is a useful indicator to assess the prognosis of patients with osteosarcoma.

Objective:To investigate the protective effect of lactoferrin(Lf) on lung injury in mice exposed to irradiation.Methods:C57BL/6 J mice were randomly divided into control group, 15 Gy irradiation group (IR group) and lactoferrin combined 15 Gy irradiation group (Lf+ IR group), with 5 mice in each group. The mice in the Lf+ 15 Gy group drank lactoferrin solution (10 mg/ml) from 3 days before irradiation and contained the whole experiments. Then, single chest 15 Gyirradiation was performed both in the IR and Lf+ IR groups. The body weight and other characteristics were monitored during the experiment. The mice were killed at day 14 after irradiation. The lung histopathology was observed by HE staining. Serum inflammatory cytokine such as HMGB1, TNF-α, IL-1β and IL-6 was determined by ELISA method . The expression of inflammatory related protein in lung tissue including HMGB1, TLR4, MyD88 and NF-κB were performed by immune histochemistry and Western blot method.Results:Compared with the control group, lung weight was significantly increased ( t=3.20, P<0.05), pulmonary hyperemia and inflammatory cell infiltration was observed in the IR group. Exposure also significantly increased serum level of TNF-α[(291.80±5.49) vs.(332.25±22.18)pg/ml]( t=3.07, P<0.05), up-regulated the expression of inflammatory related protein in lung tissue ( t=4.04, 4.78, 3.77, 6.14, P<0.05). Lactoferrin intervention (Lf+ IR group) significantly decreased lung weight ( t=2.18, P<0.05), alleviated histopathologic changes, decrease serum levels of HMGB1, TNF-α and IL-1β ( t=4.67, 2.97, 3.49, P<0.05). On the other hand, lactoferrin intervention decreased the positive cell number of HMGB1 and NF-κB, and down-regulated the protein expression of HMGB1, TLR4, MyD88 and NF-κB in lung tissues, with significant difference with the IR group ( t=8.06, 9.80, 3.07, 5.56, P<0.05). Conclusions:Lactoferrin plays the protective effect of radiation-induced lung injury through the downregulation of inflammatory response, such as HMGB1/TLR4/MyD88/NF-κB signaling pathway.

Objective To observe the clinical application of combined detection of troponin T(cTnT),myoglobin(Myo) and NT-ProBNP in the diagnosis of myocardial infarction(MI).Methods A total of 913 cases of acute chest pain complaints to our hospital for examination and treatment from January 2012 to December 2015 were selected and divided into the acute MI group and non-acute MI group according to the final diagnostic results.The cTnT,Myo and NT proBNP levels were detected in all subjects.The differences of cTnT,Myo and NT-proBNP levels were observed in the two groups.The sensitivity and specificity of single indicator detection,2-indicator combined detection and 3-indicator combined detection for diagnosing MI were observed.Results The levels of cTnT,Myo and NT-proBNP in the acute MI group were significantly higher than those in the non-acute MI group,the difference was statistically significant(P<0.05).The sensitivity and specificity of the two-indicator combined detection were higher than those of cTnT,Myo and NT-proBNP single detection,the sensitivity and specificity of the 3-indicator combined detection were 95.18% and 89.86% respectively,which were significantly higher than those of the single indicator test and the two-indicator combined detection.Conclusion The combined examination of cTnT,Myo and NT-proBNP has important significance in the diagnosis of MI,can improve the specificity and sensitivity of MI diagnosis and provides a reliable basis for clinical treatment.

Objective: To evaluate the therapeutic efficacy and safety of immunosuppressive therapy (IST) combined with recombinant human thrombopoietin (rhTPO) for severe aplastic anemia (SAA) in pediatric patients. Method: A retrospective case-control study was conducted and the clinical data of 45 pediatric patients with de novo SAA admitted to the Anemia Diagnosis and Treatment Center of Chinese Academy of Medical Sciences & Blood Disease Hospital during the period from December 2009 to December 2014 were analyzed. Among them, 15 patients were treated with the regimen of IST together with rhTPO and 30 patients were given IST treatment only. The variation characteristics of the peripheral blood routine as well as the transfusion of blood products was dynamically observed, and the therapeutic efficacy was assessed respectively after 3, 6 and 12 months after the treatment. In the meantime, adverse effects related to rhTPO application were recorded. Thereafter, the statistics of the two groups were compared by non-parametric rank sum test. Result: Among 45 pediatric patients, there were 26 male and 19 female, and the median age was 11 years (6-14). The number of patients received good hematological response(complete remission (CR) plus good partial response (GPR)) in the combinatory group versus vs. the IST group was 6 vs. 3 patients (χ²=3.906, P=0.048) at the 3rd month, 7 vs. 7 patients (χ²=1.568, P=0.210) at the 6th month, and 13 vs. 14 patients (χ²=6.667, P=0.01) at the 12th month respectively. For those achieved good hematological response at the 3rd month, the amount of platelets transfusion and red blood cells transfusion of the combined group were both less than that of the IST group during the period from the 10th to the 12th weeks (platelets transfusion: 1.4 U vs. 2.9 U, t=-3.523, P=0.002; red blood cells transfusion: 0.8 U vs. 2.6 U, t=-2.392, P=0.026). No serious adverse effect related to rhTPO application was observed in the IST combined with rhTPO group. Conclusion Application of rhTPO can improve the short-term therapeutic efficacy of IST for pediatric SAA, alleviate transfusion dependence, and has a good safety profile.

Osteosarcoma is the most common primary sarcoma of bone, and it is a leading cause of cancer death among adolescents and young adults. However, the molecular mechanism underlying osteosarcoma carcinogenesis remains poorly understood. Recently, cyclin-dependent kinase 6 (CDK6) was identified as an important oncogene. We found that CDK6 protein level, rather than CDK6 mRNA level, is much higher in osteosarcoma tissues than in normal adjacent tissues, which indicates a post-transcriptional mechanism involved in CDK6 regulation in osteosarcoma. MiRNAs are small non-coding RNAs that repress gene expression at the post-transcriptional level and have widely been shown to play important roles in many human cancers. In this study, we investigated the role of miR-29b as a novel regulator of CDK6 using bioinformatics methods. We demonstrated that CDK6 can be downregulated by miR-29b via binding to the 3'-UTR region in osteosarcoma cells. Furthermore, we identified an inverse correlation between miR-29b and CDK6 protein levels in osteosarcoma tissues. Finally, we examined the function of miR-29b-driven repression of CDK6 expression in osteosarcoma cells. The results revealed that miR-29b acts as a tumor suppressor of osteosarcoma by targeting CDK6 in the proliferation and migration processes. Taken together, our results highlight an important role for miR-29b in the regulation of CDK6 in osteosarcoma and may open new avenues for future osteosarcoma therapies.
3' Untranslated Regions ; Animals ; Base Sequence ; Bone Neoplasms ; metabolism ; pathology ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Cyclin-Dependent Kinase 6 ; antagonists & inhibitors ; genetics ; metabolism ; Humans ; Mice ; MicroRNAs ; metabolism ; Osteosarcoma ; metabolism ; pathology ; RNA Interference ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; metabolism ; Rats ; Sequence Alignment ; Up-Regulation

Objective:To observe the protective effect of deproteinized extract of calf blood (DECB)on the ethanol-induced liver injury of the mice,and to preliminaryly discuss its mechanism. Methods:Sixty healthy ICR mice were divided into control group,model group,positive drug group,low,medium and high doses of DECB groups (n=10).By intragastric administration,the mice in control group were given 20 mL·kg-1 saline solution, the mice in low,medium and high doses of DECB groups were administrated with 0.125,0.250,0.500 g·kg -1 DECB,and the mice in positive drug group were administrated with 0.63 g·kg -1 Hugan Tablets;once a day for 30 d. 1 h after the last administration,except control group,the mice in other groups were administrated with one-time grant of 50% ethanol 14 mL·kg -1 ,and fasted for 16 h to establish the models of acute alcohol liver injury.The endurance alcohol time and drunk time of the mice were determined,the activities of aspartate aminotransferase (ALT)and alanine transaminase (AST)activity in serum of the mice were detected,the levels of triglyceride (TG),glutathione (GSH)and malonic dialdehyde (MDA)in liver tissue were determined,and the pathological changes of liver tissue were detected.Results:Compared with model group,the drunk symptoms of the mice in different doses of DECB groups were obviously reduced,the endurance time of the mice in high dose of DECB group and positive drug group was prolonged (P <0.05),and the drinking time was shortened (P <0.05);the ALT and AST activities in serum in mediun and high doses of DECB groups were significantly lower than those in model group (P <0.05).Compared with model group,the MDA and TG levels in liver tissue of the mice in medium and high doses of DECB groups and positive drug group were obviously reduced,and the GSH levels were increased (P <0.05);compared with model group,the pathological damages of liver tissue of the mice in high dose of DECB group caused by ethanol were significantly reduced.Conclusion:DECB can improve ethanol-induced liver injury which may be related to the inhibition of hepatic oxidative stress response.