Aqueous extract of Polygonatum sibiricum ameliorates ethanol-induced mice liver injury via regulation of the Nrf2/ARE pathway.

This study investigates the hepatoprotective effect of the aqueous extract of Polygonatum sibiricum (AEPS) against ethanol-induced oxidative stress and explores underlying mechanisms. AEPS was administered by gavage to ICR mice for 30 days. The experimental mice were fed a 5% (v/v) ethanol on last 10 days and followed by a single megadose of ethanol (5 g/kg) to induce ethanol-induced liver injury. Pretreatment with AEPS significantly suppressed the ethanol-induced elevation of aminotransferase activities, total bilirubin (TBIL) level, triglyceride level, and alleviated liver histopathological lesions. Meanwhile, AEPS reduced the level of oxidative stress in the liver and significantly suppressed the mRNA levels of NOX1, p67phox, gp91phox, and CYP2E1. Additionally, AEPS significantly increased the mRNA and protein levels of Nrf2 and its downstream antioxidant genes and promoted the nuclear translocation of Nrf2 in mice liver. Therefore, AEPS can effectively reduce ethanol-induced liver injury via regulation of the Nrf2/ARE pathway. PRACTICAL APPLICATIONS: Alcohol abuse and alcoholism have become a serious public health problem worldwide. Since liver is the major organ of alcohol metabolism, the most impactful damage of alcohol occurs in the liver. Polygonatum sibiricum is a traditional Chinese galenical and it also can be used as food ingredients. Most studies have reported that polysaccharide, flavonoids and saponins are the main bioactive compounds in Polygonatum sibiricum which play important roles in anti-oxidation. AEPS is the aqueous extract of Polygonatum sibiricum and AEPS can protect the mice liver against ethanol-induced oxidative damage. Thus it can be potential antioxidants to product hepatoprotective food and the study also provides a theoretical basis for the development and application of food about Polygonatum sibiricum.

CXCR3 from chemokine receptor family correlates with immune infiltration and predicts poor survival in osteosarcoma.

BACKGROUND: Chemokine receptors have a crucial role in regulating tumor mediating immunity and are also implicated in the prognosis of some cancers. Here, the association between CXC chemokine receptors (CXCR2-5) and prognosis in osteosarcoma was studied. METHODS: Differences between CXCR2, CXCR3, CXCR4, and CXCR5 expression and overall survival (OS) and event-free survival (EFS) were compared using Kaplan-Meier analyses. The associations of CXCR3 expression with clinical features and the prognosis were also analyzed. The signaling pathways modulated by CXCR3 were investigated. The correlations between CXCR3 and immune infiltrates were investigated. RESULTS: The expression of CXCR2, CXCR4, and CXCR5 was not associated with the prognosis, but CXCR3 low expression was correlated with worse OS and EFS of osteosarcoma, especially for female, patients aged less than 15.1 years, or patients without metastasis. Low CXCR3 expression was related to tumor site and histologic response (P<0.05), but not associated with other clinical characteristics. Multivariate Cox analysis revealed that CXCR3 remained independently associated with the prognosis, especially for OS (hazard ratio (HR) = 3.26, 95% CI = 1.15-9.24, P=0.026). The cell adhesion, apoptosis, metabolism, KRAS, P53, NOTCH, reactive oxygen species (ROS), PI3K/Akt/mTOR, vascular endothelial growth factor (VEGF), inflammation, and immune-related pathways such as IL-6/JAK/STAT3, TNF-α via NF-κB, Toll/NOD-like receptor, and complement were modulated by CXCR3. CXCR3 expression showed an especially positive correlation with immune infiltration of T cells CD8, macrophages M1, plasma cells, and NK cells activated. CONCLUSIONS: CXCR3 may be an independent risk factor for the prognosis and is most likely to benefit from immunotherapy in osteosarcoma.

[Application of reverse dermal revascularization combined with vacuum sealing drainage in the large area of skin avulsion of the lower extremities].

OBJECTIVE: To summarize the clinical effect of emergency subcutaneous vascular network reverse skin replantation combined with vacuum sealing after drainage of large area skin avulsion injury. METHODS: Clinical data of 30 patients with extensive skin avulsion of the lower limb treated between July 2010 and March 2018 were collected. There were 20 males and 10 females, ranging in age from 16 to 67 years old, with an average of(48±13) years old. Cause of injury: 19 cases of car accident injury, 11 cases of crush injury. The surgery time was 3 to 10 h, with an average of (5±1) h. All cases were completely debrided in stage I. The subdermal vascular network was reversed and skin grafted with multiple incision drainage combined with negative pressure closed drainage technique for 7 to 10 days. The wounds were removed by VSD observation:if the necrotic area is large, debridement is required. After the granulation growth of the wound is satisfactory, the skin grafting is performed again after electrification; the small area of necrotic skin strengthens the dressing and heals. RESULTS: 30 patients were followed up for 7 to 48 months, with an average of (20±11) months.No infection in 1 case appeared, 30 patients, living area more than 85% of the wound after treatment survival in the stage I; The skin necrosis ranged from about 12% in 5 patients in the stage II. The second stage was healed after redebriding free skin grafts. The other patients were healed after the dressing, capillary meshwork layer of skin color, good elasticity, feeling, wearable pressure, each joint activities is good, no obvious skin adhesion cause physical activity is limited. CONCLUSIONS: Reverse skin grafting combined with VSD for the treatment of large skin avulsion of lower limb can greatly reduce wound infection rate, promote the application of skin and wound, conducive to drainage, improve the survival rate of reverse skin grafting and improve the function of lower limb joints.

MicroRNA-181c Suppresses the Biological Progression of Osteosarcoma via Targeting SMAD7 and Regulating Transforming Growth Factor-ß (TGF-ß) Signaling Pathway.

BACKGROUND Osteosarcoma is a primary bone aggressive cancer, affecting adolescents worldwide. Increasing evidence suggests that dysfunction of microRNAs (miRNAs) plays a pivotal role in malignancies. The aim of this study was to evaluate the potential functions of miR-181c and verifying its regulatory effects on SMAD7 in osteosarcoma. MATERIAL AND METHODS The expressions of miR-181c and SMAD7 in osteosarcoma were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, invasion and migration abilities were assessed using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) and Transwell assay. Bioinformatics analysis and luciferase reporter assay were used to explore the interaction between miR-181c and SMAD7. Western blot was performed to determine the functions of miR-181c on osteosarcoma cell epithelial-to-mesenchymal transition (EMT) and transforming growth factor-ß (TGF-ß) signaling pathway. RESULTS Decreased expression levels of miR-181c and SMAD7 were identified in osteosarcoma using qRT-PCR. The downregulated miR-181c and SMAD7 expressions indicated poor prognosis of osteosarcoma patients. Moreover, miR-181c overexpression prominently repressed osteosarcoma cell proliferation, invasion, and migration abilities via modulating EMT and TGF-ß signaling pathway. SMAD7 functioned as an important target for miR-181c in osteosarcoma cells. Furthermore, upregulation of miR-181c dramatically suppressed osteosarcoma tumorigenesis in vivo. CONCLUSIONS These findings indicated that miR-181c suppressed osteosarcoma progression, providing new insight into the pathogenesis and representing a potential therapeutic target for osteosarcoma.

Decreased expression of STAT5A predicts poor prognosis in osteosarcoma.

BACKGROUND: Signal transducer and activator of transcription 5 (STAT5) plays a key role in the malignancy of many tumors and has been identified as a therapeutic target. However, the role of STAT5A in osteosarcoma is still unclear. METHODS: 98 osteosarcoma patients were obtain from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET). The relationship between STAT5A and clinical features was analyzed using the Wilcoxon signed-rank test and logistic regression. Kaplan-Meier method, univariate and multivariate Cox regression analyses were performed to assess the prognostic value in event-free survival (EFS) and overall survival (OS). Gene Set Enrichment Analysis (GSEA) was performed. RESULTS: STAT5A low expression was not linked to age, gender, tumor site, surgical approach, tumor region, histologic response, and metastasis, but was correlated with progression (OR = 5.2, P = 0.012). Kaplan-Meier survival curve showed that patients with STAT5A low expression had worse EFS and OS than those with STAT5A high expression (P < 0.01). Furthermore, the multivariate analysis revealed STAT5A was an independent prognostic factor for poor OS (HR = 3.29, P = 0.0408)) and EFS (HR = 7.29, P = 0.0025). GSEA showed that the complemen, metabolism, apoptosis, interferon-gamma response, inflammatory response, Notch, Kras, reactive oxygen species, VEGF, IL-6/JAK/STAT3, IL-2/Stat5, B-cell receptor, and p53 pathways were significantly associated with the STAT5A gene. CONCLUSIONS: STAT5A may be a novel prognostic factor for osteosarcoma and may act as a molecular target in the treatment of osteosarcoma.

[Meta analysis of unilateral condylar replacement and high tibial osteotomy in the treatment of medial compartment osteoarthritis of the knee].

OBJECTIVE: Meta-analysis was used to compare the clinical efficacy of high tibial osteotomy(HTO) and unicondylar arthroplasty (UKA) in the treatment of medial compartment osteoarthritis (MIOA) and provide a better surgical choice for patients with MIOA. METHODS: The Cochrane Library (Issue 6, 2017), PubMed, Ovid, ELSIVE, CNKI and Wanfang databases were searched by a computer. Literatures on HTO and UKA for MIOA from January 1, 1970 to June 30, 2017, including complications, knee joint score, knee mobility, revision rate and excellent and good rate, were searched and screened out according to the inclusion criteria, and strict quality evaluation was carried out. RevMan 5.0 software provided by Cochrane collaboration network was used to conduct the meta-analysis of the included research results and to test the heterogeneity of the data. RESULTS: Total 13 articles met the inclusion criteria, and the total sample size was 1 043. Among them, 462 were HTO treatment group and 581 were UKA treatment group. By comparison between HTO treatment group and UKA treatment group, there were significant differences in the contralateral deterioration rate[WMD=3.21, 95%CI(1.13, 9.10)], pre-operative knee range of motion[WMD=6.55, 95%CI(1.44, 11.66)], Lysholm knee score[WMD=-3.15, 95%CI(-4.77, -1.53)], complications[WMD=2.78, 95%CI(1.52, 5.11], revision rate[WMD=1.81, 95%CI(1.17, 2.80)], the rate of excellent and good[WMD=0.49, 95%CI(0.30, 0.80)], and femorotibial angle changes[WMD=-2.37, 95%CI, (-3.63, -1.11)](P<0.05). There were no significant differences between the HTO treatment group and the UKA treatment group in patellofemoral deterioration rate[WMD=1.59, 95%CI(0.65, 3.84)] and the free walking speed[WMD=-0.02, 95%CI(-0.09, 0.04)](P>0.05). CONCLUSIONS: Based on the limited data, high tibial osteotomy is a better choice for the treatment of medial compartment osteoarthritis in the comparison of short and medium-term clinical outcomes, and long-term clinical outcomes may need further study.

The biomechanical study of rupture of Achilles Tendon and repair by different suture techniques.

OBJECTIVE: To study the biomechanical properties of different suture methods, and to provide evidence for the clinical application of this suture methods in repairing acute Achilles tendon rupture. METHODS: Twenty four fresh frozen cadaver Achilles tendon specimens were collected and randomly divided into three groups (n=8), Group-A Bunnell suture method, Group-B Bosworth suture and Group-C anchor suture respectively. 5 N tensions were applied to tighten the tendon. The actual length of the tendon between the upper and lower clips was measured with a ruler. The length of the long axis and the short axis of the three sections of the tendon was measured by vernier caliper. The cross sectional area of the tendon was calculated according to the elliptical area formula and the mean value was obtained. RESULTS: There was no significant difference in the length and cross-sectional area of each tendon among three groups (F=0.26, P=0.86; F=0.09, P=0.96). There was no significant difference in the maximum load of tendon and failure displacement in Group A and B (P>0.05). The maximal load of Group-C was significantly larger than that of Group A and B (P<0.05), and there was no significant difference between the failure displacement and Group A and B (P>0.05). CONCLUSION: Three suture methods can provide good biomechanical properties, but the anchor suture is more effective in solving the shortcomings of traditional methods. It is a safe and effective method, and is worthy of promotion.

P16 protein expression as a useful predictive biomarker for neoadjuvant chemotherapy response in patients with high-grade osteosarcoma: A systematic meta-analysis under guideline of PRISMA.

BACKGROUND: Neoadjuvant chemotherapy for patients with high-grade osteosarcoma has highly improved the clinical survival. However, the prognostic and predictive role of P16 expression after neoadjuvant chemotherapy remains unclear. We first determined whether P16 expression can become a potential prognostic and predictive biomarker in high-grade osteosarcoma. METHODS: This meta-analysis was conducted based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guideline. Eligible studies were pooled and the overall odds ratios (ORs) and hazard ratios (HRs) with the corresponding 95% confidence intervals (95% CIs) were calculated in this analysis. RESULTS: Four studies involving a total of 527 patients with high-grade osteosarcoma receiving neoadjuvant chemotherapy were identified. We did not find that P16 expression was correlated with sex status, histologic subtype, and tumor site (P > .1). P16 expression was found to be significantly associated with a "good" response to neoadjuvant chemotherapy (OR = 4.69, P < .001). A significant relationship was observed between p16 expression and pathologic complete response after neoadjuvant chemotherapy using multivariate analysis (OR = 9.63, P = .001). The expression of the P16 was not associated with clinical outcomes in overall survival (OS) and disease-free survival (DFS) by multivariate analysis (OS: P = .448; DFS: P = .263). CONCLUSIONS: The use of P16 expression could become a promising predictive biomarker of the response to neoadjuvant chemotherapy in the white population with high-grade osteosarcoma. However, it was not correlated with the prognosis of patients in OS and DFS. More clinical researches are very essential in Asians in the future.

[Biomechanical research on internal fixation methods of posterior pelvic ring fracture dislocation].

OBJECTIVE: To investigate the biomechanical differences of three internal fixation approaches, namely improved Galveston (IG), reconstruction plate (RP), and iliosacral screw (LS) to the posterior pelvic ring fracture dislocation and provide experimental evidence for the clinical application of proper internal fixation method. METHODS: Six donated fresh adult cadaver pelvic specimens (age averaged 45 years old) were numbered randomly and their normal biomechanics were tested by the measure instrument (MTS855 Mini-Blonix). The displacement values of normal pelvis were measured under the vertical compression (800 N) and reverse direction compression (8 N x m). Then they were made into left Denis I pelvic fracture and fixed with the IG, RP, and LS, respectively, in different orders. Biomechanics test was conducted on the fixed pelvis from both the vertical and the reversed directions. RESULTS: Concerning the direction of verticality and torsion, the order of fracture displacement from small to large was the normal pelvis, LS, IG and RP. There was no significant difference between LS and the normal pelvis (P > 0.05), and the differences between other tow groups were significant (P < 0.05). CONCLUSION: The LS fixation can provide better stability for posterior pelvic ring fracture dislocation when compared with IG and RP.