Objective: To investigate the effects of human adipose-derived mesenchymal stem cells (ADSCs) and platelet-rich plasma (PRP) on healing of wounds with full-thickness skin defects in mice. Methods: ADSCs were isolated from the lumbar and abdominal fat donated voluntarily by a healthy woman undergoing liposuction in the Department of Plastic Surgery of Guangzhou General Hospital of Guangzhou Military Area Command, and the cells were cultured and identified. ADSCs of the second passage were used in the following experiments. The venous blood of the volunteer was taken, and PRP was obtained by secondary centrifugation. Thirty-six C57BL/6 mice were divided into simple injury group (n=12), simple ADSCs treatment group (n=12), and ADSCs+ PRP treatment group (n=12) according to the random number table. Each mouse was inflicted with a 1 cm×1 cm wound with full-thickness skin defect on the back. Immediately after injury, the wounds of mice in simple injury group were subcutaneously injected with 1 mL normal saline, the wounds of mice in simple ADSCs treatment group were subcutaneously injected with 1 mL phosphate buffer solution-blended ADSCs suspension (with concentration of 5×10⁵ /mL, the same below), and the wounds of mice in ADSCs+ PRP treatment group were subcutaneously injected with 1 mL mixture of PRP and ADSCs (1∶2 volume ratio). Three mice in each group were taken on post injury day (PID) 3, 5, 7, and 14 to observe the gross condition of wound, and the wound healing rate was calculated. On PID 3, 5, and 7, the non-healing wound tissue and 0.5 cm normal skin tissue around the wound margin were taken after gross observation. The inflammation, re-epithelialization, and angiogenesis of tissue were observed by hematoxylin and eosin staining, and the re-epithelialization rate was calculated. The collagen synthesis of tissue was observed by masson staining. Immunohistochemistry was used to observe the expression of macrophages of tissue samples collected on PID 3 and 5. Data were processed with analysis of variance of factorial design and Least-Significant Difference test. Results: (1) On PID 3, the wounds of mice in ADSCs+ PRP treatment group were with granulation tissue regeneration, redness, and swelling, and the wounds of mice in the other two groups were ruddy and with effusion. On PID 5, the wounds of mice in ADSCs+ PRP treatment group had less redness and swelling, which were dry with obvious scab, and wounds of mice in the other two groups were obviously red and swollen. On PID 7, scab formed basically on wounds of mice in the three groups. On PID 14, the wounds of mice in the three groups basically healed, and their crusts were off. On PID 3, 5, 7, and 14, the wound healing rates of mice in ADSCs+ PRP treatment group were obviously higher than those of the other two groups (P<0.05 or P<0.01). On PID 5 and 7, the wound healing rates of mice in simple ADSCs treatment group were obviously higher than those of simple injury group (P<0.01). (2) On PID 3, granulation tissue regeneration of wounds in ADSCs+ PRP treatment group was more than that in the other two groups. On PID 5, inflammatory reaction of wounds of mice was mild in ADSCs+ PRP treatment group, which was severe in the other two groups. On PID 7, the re-epithelialization process of wounds of mice was almost completed in ADSCs+ PRP treatment group, and the number of new vessels was more in ADSCs+ PRP treatment group than in the other two groups. The migration distance of regenerated epithelia around the wound edge in simple injury group and simple ADSCs treatment group was short. On PID 3, 5, and 7, the re-epithelialization rates of wounds of mice in ADSCs+ PRP treatment group were (37.6±4.5)%, (59.1±1.3)%, and (89.2±4.3)%, respectively, significantly higher than (25.7±1.5)%, (34.5±4.4)%, and (50.8±2.7)% in simple injury group and (29.1±0.8)%, (42.6±2.9)%, and (72.9±3.0)% in simple ADSCs treatment group (P<0.01). On PID 5 and 7, the re-epithelialization rates of wounds of mice in simple ADSCs treatment group were significantly higher than those in simple injury group (P<0.05 or P<0.01). (3) On PID 3 and 5, a quite large number of new collagen fibers appeared in granulation tissue of wounds of ADSCs+ PRP treatment group, while the collagen fibers in the other two groups were less. On PID 7, the granulation tissue of mice in ADSCs+ PRP treatment group decreased, and a large number of new collagen fibers appeared. The collagen fibers in wounds tissue of mice in simple ADSCs treatment group increased, while the collagen fibers deposited in wounds tissue of mice in simple injury group was still less. (4) On PID 3 and 5, the numbers of macrophages in wounds tissue of mice in simple ADSCs treatment group were 4.7±0.6 and 5.3±0.6 respectively, obviously lower than 6.3±0.6 and 7.7±0.6 in injury group (P<0.05 or P<0.01); the numbers of macrophages in wounds tissue of mice in ADSCs+ PRP treatment group were 3.0±1.1 and 2.7±0.5, significantly lower than those in the other two groups (P<0.05 or P<0.01). Conclusions Human PRP and ADSCs are involved in the early inflammation, metaphase of tissue proliferation, and re-epithelialization and shaping process of late stage of wounds with full-thickness skin defects in mice. The combination of ADSCs and PRP may be a comparatively good combination to improve the speed and quality of wound healing.

Objective:To investigate risk factors for early mortality (EM) in patients with newly diagnosed multiple myeloma (NDMM) and to build an EM-predictive model.Methods:In a cohort of 275 patients with NDMM, risk factors for EM at 6, 12, and 24 months after diagnosis (EM6, EM12, and EM24, respectively) were determined to establish a model to predict EM.Results:The rates of EM6, EM12, and EM24 were 5.5% , 12.7% , and 30.2% , respectively. The most common cause for EM was disease progression/relapse, accounting for 60.0% , 77.1% , and 84.3% of EM6, EM12, and EM24, respectively. EM6 was associated with corrected serum calcium >2.75 mmol/L and platelet count <100×10 9/L, whereas risk factors for EM12 included age >75 years, ISS Ⅲ, R-ISS Ⅲ, corrected serum calcium >2.75 mmol/L, serum creatinine >177 μmol/L, platelet count <100×10 9/L, and bone marrow plasma cell ratio ≥ 60% . In addition to the risk factors for EM12, EM24 was also associated with male sex and 1q21 gain. By multivariate analysis, age >75 years, platelet count <100×10 9/L, and 1q21 gain were independent risk factors for EM24 but there were no independent risk factors significantly associated with EM6 and EM12. Using a scoring system including these three risk factors, a Cox model for EM24 was generated to distinguish patients with low (score<3) and high (score ≥ 3) risk. The sensitivity and specificity of the model were 20.7% and 99.2% , respectively. Further, an internal validation performed in a cohort of 183 patients with NDMM revealed that the probability of EM24 in high-risk patients was 26 times higher than that in low-risk patients. Moreover, this model was also able to predict overall survival. The median overall survival of patients with scores of 0, 1, 2, 3, 4, and 5 were 59, 41, 22, 17.5, and 16 months, respectively. Conclusion:In the study cohort, the EM6, EM12, and EM24 rates were 5.5% , 12.7% , and 30.2% , respectively, and disease progression or relapse were main causes of EM. An EM24-predictive model built on three independent risk factors for EM24 (age>75 years, platelet count<100×10 9/L, and 1q21 gain) might predict EM risk and overall survival.

Objective:To improve the prognosis stratification, especially early mortality(EM), of elderly patients with newly diagnosed multiple myeloma(NDMM).Methods:In this retrospective study, univariate and multivariate Cox regression analysis were conducted to identify the independent prognostic factors associated with overall survival(OS)and the chi-square test and multivariate Logistic analysis were used to identify the prognostic factors associated with EM in 223 elderly patients(age≥65 years)with NDMM from three centers in the country.Results:Increased NT-pro-BNP(≥300 pg/ml), ECOG-PS≥2 and stage Ⅲ R-ISS were identified as three independent adverse prognostic factors of OS.The rates of EM3, EM6, EM12 and EM24 were 12.1%, 20.1%, 32.2% and 60%, respectively.The most common cause for EM6(particularly EM3)was disease-related complications resulting from ineligibility for treatment due to poor physical performance, severe organ dysfunction or treatment discontinuation due to treatment intolerance, while the most common cause for EM12(particularly EM24)was disease progression or relapse mainly as a result of inadequate treatment.R-ISS staging failed to predict EM, while decreased eGFR, ECOG-PS≥2, and increased NT-pro-BNP were able to estimate the risk of EM, with increased NT-pro-BNP as a common independent factor for EM12( P=0.03)and EM24( P=0.015). Conclusions:R-ISS staging, which primarily reflects MM biology, cannot predict EM.However, factors such as NT-pro-BNP, eGFR and ECOG-PS associated with frailty and impairment of organ functions can be used to estimate the risk of EM, among which NT-pro-BNP may be the most important independent factor for EM.Therefore, incorporation of these frailty-related biomarkers into R-ISS staging may be able to more precisely estimate the prognosis and particularly early death of elderly patients with NDMM.

BACKGROUND:Cardiac dysfunction due to spinal cord injury is an important factor of death in patients with spinal cord injury;however,the specific mechanism is still not clear.Therefore,revealing the mechanism of cardiac dysfunction in spinal cord injury patients is of great significance to improve their quality of life and survival rate. OBJECTIVE:To investigate the mechanism of luteolin in improving serum-induced myocardial cell death in spinal cord injury rats. METHODS:Allen's impact instrument was used to damage the spine T9-T11 of male SD rats to establish a spinal cord injury model meanwhile a sham operation group was set as the control group.The serum of rats of each group was collected.H9c2 cells were divided into a blank control group,a sham operated rat serum group,a spinal cord injury rat serum group and a luteolin pretreatment group.The cells in blank control group were only cultured with ordinary culture medium.The cells in the sham operated rat serum group were treated with medium containing 10%serum from sham operated rat.The cells in the spinal cord injury rat serum group were treated with medium containing 10%serum from spinal cord injury rat.The cells in the luteolin pretreatment group were precultured with a final concentration of 20 μmol/L luteolin for 4 hours and then changed to a medium containing 10%rat serum from spinal cord injury rat.After 24 hours of culture,the survival rate of each group of H9c2 cells was measured by CCK-8 assay.Western blot assay was used to detect the expression of autophagy related protein LC3 and p62 in H9c2 cells in each group. RESULTS AND CONCLUSION:Compared with the blank control group,there was no significant change in cell survival rate in the sham operated rat serum group(P>0.05).Compared with the sham operated rat serum group,the cell survival rate(P<0.01)and the expression of LC3 protein(P<0.05)in spinal cord injury rat serum group was significantly reduced,and the expression of p62 protein was significantly increased(P<0.05).Compared with the spinal cord injury rat serum group,the survival rate of cells in the luteolin pretreatment group significantly increased(P<0.000 1);the expression of LC3 protein significantly increased(P<0.05),and the expression of p62 protein significantly decreased(P<0.05).The results indicate that luteolin may improve myocardial cell death induced by serum from rats with spinal cord injury by promoting autophagy.

Some Chinese herbs have been used to prevent and treat diseases, and are also used as common food ingredients. These Chinese herbs are potential resource for research and development of new drugs. Leek roots is a typical medicine of food and medicine continuum. It has a long history of medicinal applications and edible food in China. In this paper, the origin, biological active components, pharmacological action and clinical application of leek roots were introduced. We hope that this review will contribute to the development of leek roots for pharmaceutical research and clinical applications, as well as related health products.

Bavachin is a dihydroflavonoid compound isolated from Psoralea corylifolia, and exhibits anti-bacterial, anti-inflammatory, anti-tumor and lipid-lowering activities. Recent attention has gradually drawn on bavachin-induced apoptosis in many human cancer cell lines. However, the anti-cancer effects and related mechanisms in colorectal cancer remain unknown. Here, we investigated the effects of bavachin on colorectal cancer in vivo and in vitro. The results showed that bavachin inhibited the proliferation of human colorectal cancer cells and induce apoptosis. These changes were mediated by activating the MAPK signaling pathway, which significantly up-regulated the expression of Gadd45a. Furthermore, Gadd45a silencing obviously attenuated bavachin-mediated cell apoptosis. Inhibition of the MAPK signaling pathway by JNK/ERK/p38 inhibitors also weakened the up-regulation of Gadd45a by bavachin. The anticancer effect of bavachin was also validated using a mouse xenograft model of human colorectal cancer. In conclusion, these findings suggest that bavachin induces the apoptosis of colorectal cancer cells through activating the MAPK signaling pathway.
Humans ; Signal Transduction ; Flavonoids/pharmacology* ; Proteins/pharmacology* ; MAP Kinase Signaling System ; Colorectal Neoplasms/metabolism* ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Cell Cycle Proteins/pharmacology*