Human Chorionic Gonadotropin Regulates the Smad Signaling Pathway by Antagonizing TGF-ß in Giant Cell Tumor of Bone.

BACKGROUND: Giant cell tumor of bone (GCTB) is a locally aggressive bone tumour aggravated by stromal cell proliferation and metastasis. OBJECTIVE: We investigated the mechanism of action of human chorionic gonadotropin (HCG) in mediating GCTB proliferation and invasion. METHODS: The expression of HCG was quantified using quantitative real-time PCR. After the primary stromal cells were isolated and identified, the function of HCG in GCTB was estimated using the cell counting kit-8, flow cytometry, scratch experiment, transwell assay, Western blot, and immunofluorescence. Moreover, the mechanism of HCG was assessed through western blotting. RESULTS: HCG expression was decreased in clinical tissue samples from patients with GCTB. We validated that HCG repressed stromal cell proliferation, migration, invasion, autophagy, and epithelial- mesenchymal transition (EMT) and promoted cell apoptosis in GCTB. We also verified that HCG repressed the autophagy and EMT of stromal cells through the Smad signaling axis in GCTB. HCG inhibited the transduction of the Smad signaling pathway by restraining the binding of the TGF-ß II receptor to ligand Activin A. CONCLUSION: HCG restrained the Smad signaling pathway by antagonizing TGF-ß signaling in GCTB. HCG may serve as a useful patent to treat GCTB.

MiR-145 inhibits the differentiation and proliferation of bone marrow stromal mesenchymal stem cells by GABARAPL1 in steroid-induced femoral head necrosis.

Steroid-induced osteonecrosis of femoral head (SANFH) involves impaired differentiation of bone marrow mesenchymal stem cells (BMSC), the mechanism of which is regulated by multiple microRNAs. Studies have shown that miR-145 is a key regulatory molecule of BMSC cells, but its mechanism in steroid-induced femur head necrosis remains unclear. The present study mainly explored the specific mechanism of miR-145 involved in SANFH. In this study dexamethasone, a typical glucocorticoid, was used to induce osteogenic differentiation of BMSC cells. Western blot, qPCR, CCK8 and flow cytometry were used to investigate the effects of miR-145 on the proliferation and differentiation of BMSC. The relationship between miR-145 and GABA Type A Receptor Associated Protein Like 1(GABARAPL1) was identified using dual luciferase reports and the effects of the two molecules on BMSC were investigated in vitro. The results showed that miR-145 was up-regulated in SANFH patients, while GABARAPL1 was down-regulated. Inhibition of miR-145 can improve apoptosis and promote proliferation and activation of BMSC. GABARAPL1 is a downstream target gene of miR-145 and is negatively regulated by miR-145. In conclusion, miR-145 regulates the proliferation and differentiation of glucocorticoid-induced BMSC cells through GABARAPL1 and pharmacologically inhibit targeting miR-145 may provide new aspect for the treatment of SANFH.

Identification of priority management areas for non-point source pollution based on critical source areas in an agricultural watershed of Northeast China.

Identification of critical source areas (CSAs) for non-point source (NPS) pollution is of great significance for environment governance and prevention. However, the CSAs are generally characterized as great spatial dispersion, and spatially heterogeneous precipitation has a great influence on the spatial distribution of nutrient yields. Therefore, we identify the CSAs for nutrient yields in an agricultural watershed of Northeast China at hydrological response units (HRUs) scale based on the Soil and Water Assessment Tool (SWAT), assess the impacts of spatially heterogeneity of precipitation on the identification of the CSAs, analyze the sensitivity of nutrient yields to precipitation by scenarios analysis method, and further identify priority management areas (PMAs) that have poor ability to retain nutrients. The results showed that the CSAs for nutrient yields identified by uniform precipitation showed greater fluctuation range and coverage area than actual precipitation; the major prevention areas of total nitrogen (TN) yield were mainly distributed in regions nearby main stem of lower reaches, while that of total phosphorus (TP) yield were mostly located in urban area nearby outlet of the watershed; the identification of the PMAs significantly decreased the CSAs for TN yield, whereas that for TP yield was no significant difference with the CSAs. This study could provide scientific guidance for the NPS pollution governance and prevention.

[Impact of Spatial Heterogeneity of Precipitation on the Area Change in Critical Source Area of Non-point Sources Pollution].

Aiming at non-point sources pollution in the agricultural areas with large topographic fluctuations and spatial differences in precipitation, a SWAT model was used to evaluate the spatial variations in the critical source areas (CSAs) of total nitrogen (TN) and total phosphorus (TP) under two precipitation scenarios, i.e., heterogeneous precipitation and uniform precipitation. A change in the CSAs identified based on the two precipitation scenarios during the study period were statistically calculated, and the relationship between the CSAs and precipitation variables was discussed. The study results showed that when the total precipitation was the same, the variation tendency of the identified CSAs for TN and TP under the two precipitation scenarios were similar, and very close for a few years. According to the results of the pair t test, the CSAs of TP were not affected by the spatial variation of precipitation, while the change in CSAs for TN was more significant under different precipitation scenarios, which is likely due to the difference in the physical properties of nitrogen and phosphorus. The correlation analysis between the CSAs of TN and TP with precipitation variables showed that the variation in the CSAs of TP was positively correlated with the precipitation variables in the same year, while the variation in the CSAs of TN was strongly related to the precipitation variables of the previous year. The results obtained in this study are of great significance for further exploring the impact of uncertainty of precipitation, which is an important driving factor, on the CSAs of non-point sources pollution and the governance of agricultural non-point sources pollution.

TBRG4 Knockdown Suppresses Proliferation and Growth of Human Osteosarcoma Cell Lines MG63 Through PI3K/Akt Pathway.

BACKGROUND: The transforming growth factor ß regulator 4 (TBRG4) has been proved to be involved in various types of tumor. However, its contribution in human osteosarcoma (OS) is still unclear. PATIENTS AND METHODS: In the present study, immunohistochemistry and quantitative real-time PCR were performed to investigate the expression of TBRG4 in OS tissues obtained from patients and three types of cell lines. The effect of TBRG4 knockdown using lentivirus on tumorigenesis was detected by CCK8, high-content screening analysis, colony formation assay and flow cytometric analysis. Bioinformatics analysis was operated to investigate related signaling pathways following TBRG4 knockdown. RESULTS: The results showed that the expression of TBRG4 increased significantly in OS tissues and MG63 cell line. TBRG4 knockdown inhibited cell proliferation, colony and tumor formation, while activating cell apoptosis. Ingenuity Pathway Analysis and Western blot assay further indicated that TBRG4 knockdown may regulate the proliferation of human MG63 cells through PI3K/Akt signaling pathway. CONCLUSION: Our results suggest that TBRG4 may become a promising therapeutic target for the treatment of human OS.

Monitoring history and change trends of ambient air quality in China during the past four decades.

This study summarized the history of ambient air quality monitoring and air pollution prevention and control, and it analyzed the spatiotemporal patterns of ambient air pollutants during 1981-2017 in China. The results showed that monitoring of ambient air quality has changed dramatically in terms of determinants, sampling methods, monitoring extent, and evaluation basis during the previous four decades. Annual average concentrations of total suspended particulates, PM10 and SO2 have shown obvious decreasing trends during the studied period. These improvements have been closely related to the considerable efforts and various approaches undertaken to prevent and control air pollution. However, although policy implementation has been decisive and, at least in part, it has been enforced effectively, significant challenges remain. Air pollution control cannot be accomplished without a long-term strategy designed to achieve clean air in all parts of China.

Effect of controlled release of brain-derived neurotrophic factor and neurotrophin-3 from collagen gel on neural stem cells.

This study aimed to examine the effect of controlled release of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) from collagen gel on rat neural stem cells (NSCs). With three groups of collagen gel, BDNF/collagen gel, and NT-3/collagen gel as controls, BDNF and NT-3 were tested in the BDNF-NT-3/collagen gel group at different time points. The enzyme-linked immunosorbent assay results showed that BDNF and NT-3 were steadily released from collagen gels for 10 days. The cell viability test and the bromodeoxyuridine incorporation assay showed that BDNF-NT-3/collagen gel supported the survival and proliferation of NSCs. The results also showed that the length of processes was markedly longer and differentiation percentage from NSCs into neurons was much higher in the BDNF-NT-3/collagen gel group than those in the collagen gel, BDNF/collagen gel, and NT-3/collagen gel groups. These findings suggest that BDNF-NT-3/collagen gel could significantly improve the ability of NSCs proliferation and differentiation.

A systematic review and meta-analysis of the use of antifibrinolytic agents in total hip arthroplasty.

BACKGROUND: Antifibrinolytic agents such as tranexamic acid (TXA), epsilon aminocaproic acid (EACA), and aprotinin are widely used to reduce bleeding and the need for transfusion in cardiac, orthopaedic, and hepatic surgery. We aimed to assess the efficacy and safety of antifibrinolytic agents in total hip arthroplasty (THA). METHODS: A systematic literature search was performed using MEDLINE, PubMed, EMBASE, and Cochrane databases, as well as the reference lists of relevant articles. Only randomised controlled trials were eligible for this study. The weighted mean difference in blood loss, number of transfusions per patient, and the summary risk ratio of transfusion requirements and deep-vein thrombosis (DVT) were calculated in the antifibrinolytic agents-treated and control groups. RESULTS: A total of 28 randomised controlled trials involving 2,131 patients were included. Patients receiving antifibrinolytic agents had a reduced total blood loss by a mean of 389.14 ml (95% CI, -483.05 to -295.23), and the number of blood transfusions per patient by 0.65 units (95% CI, -1.19 to -0.12). Antifibrinolytic agents led to a significant reduction in transfusion requirements (RR 0.55; 95% CI, 0.43 to 0.70) and no increase in the risk of DVT (RR 0.85; 95% CI, 0.51 to 1.42). CONCLUSIONS: Our meta-analysis demonstrated that antifibrinolytic agents significantly reduce blood loss and blood transfusion requirements while not increasing the risk of DVT in patients undergoing total hip arthroplasty.

Use of aprotinin to reduce blood loss and transfusion in major orthopedic surgery: a meta-analysis.

BACKGROUD: Conflicting reports have been published regarding the effectiveness and safety of aprotinin in reducing blood loss and transfusion in patients undergoing orthopedic surgery. We performed a meta-analysis to evaluate the effectiveness and safety of aprotinin in reducing blood loss and transfusion in major orthopedic surgery. MATERIALS AND METHODS: MEDLINE, PubMed, EMBASE and Cochrane databases were searched for relevant studies. Only randomized controlled trials were eligible for this study. The weighted mean difference in blood loss, and number of transfusions per patient and the summary risk ratio of transfusion requirements, and deep-vein thrombosis (DVT) were calculated in the aprotinin-treated group and the control group. RESULTS: Eighteen randomized controlled trials involving 1276 patients were included. The use of aprotinin reduced total blood loss by a mean of 498.88 ml (95% confidence interval [CI]; -735.03 to -262.72), intra-operative blood loss by a mean of 246.11 ml (95% CI; -352.11 to -140.11), post-operative blood loss by a mean of 169.11 ml (95% CI; -234.06 to -105.55), the number of blood transfusions per patient by 0.93 units (95% CI; -1.36 to -0.51). Aprotinin led to a signficant reduction in transfusion requirements (RR 0.59; 95% CI; 0.51 to 0.69) and no increase in the risk of DVT (RR 0.58; 95% CI; 0.38 to 1.08). CONCLUSION: The meta-analysis shows that aprotinin could significantly reduce blood loss and blood transfusion requirements in patients undergoing orthopedic surgery, and it did not appear to increase the risk of DVT.

The use of tranexamic acid to reduce blood loss and transfusion in major orthopedic surgery: a meta-analysis.

BACKGROUND: Conflicting reports have been published regarding the effect of tranexamic acid (TXA) on reducing blood loss and transfusion in patients undergoing orthopedic surgery. We performed a meta-analysis to evaluate the effectiveness and safety of TXA treatment in reducing blood loss and transfusion in major orthopedic surgery. MATERIALS AND METHODS: MEDLINE, PubMed, EMBASE, and Cochrane databases were searched for relevant studies. Only randomized controlled trials were eligible for this study. The weighted mean difference in blood loss, number of transfusions per patient, and the summary risk ratio of transfusion and deep vein thrombosis (DVT) were calculated in the TXA-treated group and the control group. RESULTS: A total of 46 randomized controlled trials involving 2925 patients were included. The use of TXA reduced total blood loss by a mean of 408.33 mL (95% confidence interval [CI], -505.69 to -310.77), intraoperative blood loss by a mean of 125.65 mL (95% CI, -182.58 to -68.72), postoperative blood loss by a mean of 214.58 mL (95% CI, -274.63 to -154.52), the number of blood transfusions per patient by 0.78 U (95% CI, -0.19 to -0.37), and the volumes of blood transfusions per patient by 205.33 mL (95% CI, -301.37 to -109.28). TXA led to a significant reduction in transfusion requirements (relative risk, 0.51; 95% CI, 0.46-0.56), and no increase in the risk of DVT (relative risk, 1.11; 95% CI, 0.69-1.79). CONCLUSIONS: TXA significantly reduced blood loss and blood transfusion requirements in patients undergoing orthopedic surgery, and did not appear to increase the risk of DVT.

[Short-term effectiveness of unicompartmental knee arthroplasty for medial compartmental knee osteoarthritis].

OBJECTIVE: To evaluate the short-term effectiveness of unicompartmental knee arthroplasty (UKA) for medial compartmental osteoarthritis of the knee. METHODS: Between January 2008 and October 2013, 18 patients with medial compartmental osteoarthritis of the knee were treated by UKA, including 11 males and 7 females with an average age of 67.2 years (range, 60-72 years). The disease duration ranged from 3 to 5 years (mean, 3.7 years). All patients had loading pain and walk-associated pain of the medial compartmental knee. The preoperative visual analogue scale (VAS) score was 6.8 ± 1.4. The full-length radiograph of lower limb and anteroposterior and lateral radiographs of the knee showed medial compartmental osteoarthritis of the knee. According to Ahlback staging, 8 knees were at stage II and 10 knees at stage III. The knee range of motion (ROM) was (112.3 ± 11.3)°, and the angle of genu varus was (13.2 ± 1.3)°. The American Hospital for Special Surgery (HSS) score was 59.0 ± 6.4. RESULTS: Primary healing of incision was obtained in all patients, and no infection or lower limb deep venous thrombosis occurred. All of the patients were followed up 6-50 months (mean, 28 months). No prosthetic loosening and dislocation or lesions of contralateral compartment and patellofemoral joint developed. At 6 months after operation, the VAS score was significantly reduced to 2.8 ± 1.2 (t = 9.20, P = 0.00); most of patients achieved significant relief of pain. The HSS score was significantly increased to 92.0 ± 3.1 (t = 19.69, P = 0.00); and the results were excellent in 12 cases, good in 5 cases, and poor in 1 case, with an excellent and good rate of 94.4%. The knee ROM was (115.2 ± 10.2)°, showing no significant difference when compared with preoperative one (t = -0.81, P = 0.23). The alignment of limbs showed that the angle of genu varus was significantly reduced to 6.8 ± 2.1)° (t = 10.99, P = 0.00). CONCLUSION: UKA has satisfactory short-term effectiveness in the treatment of medial compartmental knee osteoarthritis, however, long-term effectiveness need further studies.

[Treatment of common fibular nerve secondary compression syndrome].

OBJECTIVE: To investigate the mechanism, diagnosis, and treatment of common fibular nerve compression syndrome secondary to sciatic nerve injury. METHODS: Based on the clinical manifestation and Tinel's sign at fibular tunnel, 5 cases of common fibular nerve secondary compression following sciatic nerve injury were identified and treated by decompression and release of fibular tunnel. All 5 cases were followed up for 13-37 months, 25 months in average, and were evaluated in dorsal flexion strength of ankle. RESULTS: The dorsal flexion strength of ankle in 4 cases increased from 0-I degrees to III-V degrees, and did not recover in 1 case. CONCLUSION: Fibular tunnel is commonly liable to fibular nerve compression after sciatic nerve injury. Once the diagnosis is established, either immediate decompression and release of the entrapped nerve should be done or simultaneous release of fibular tunnel is recommended when the sciatic nerve is repaired.