Astragaloside IV inhibits colorectal cancer metastasis by reducing extracellular vesicles release and suppressing M2-type TAMs activation.

Ethnopharmacological relevance: Tumour-derived extracellular vesicles (TEVs) have been confirmed to facilitate colorectal cancer (CRC) metastasis by remodelling the tumour microenvironment (TME). Drugs targeted TEVs is considered as a promising therapeutic strategy for cancer treatment. Traditional Chinese medicine (TCM) plays a vital role in improving the prognosis of CRC patients and eventually CRC patients with distant metastasis. Although the anti-tumour effects of active compounds from TCM prescriptions are observed widely, the molecular mechanisms remain unknown. Aim of the study: This study aims to investigate the effects of active compounds in our library of TCM on preventing CRC metastasis, and also explore the potential mechanisms from the perspective of TEVs. Materials and methods: The effects of active compounds on the proliferation of CRC cells were determined by CCK-8 assay. TEVs were extracted from MC38 cells by ultracentrifugation and characterized by electron microscopy, Nanosight NS300 and western blotting. The TEV particles were quantified by Nanosight NS300. The potential mechanism by which astragaloside IV (ASIV) reduced TEV secretion was determined by western blotting. RAW264.7 cells were cocultured with the conditioned medium (CM) of MC38 cells treated with or without ASIV, and the activation of tumour-associated macrophages (TAMs) was assessed by immunofluorescence and quantitative polymerase chain reaction (qPCR). The migration of CRC cells was measured by wound healing and Transwell assay. A spleen-to-liver metastasis model of colorectal cancer was used to confirm the efficiency of ASIV in vivo. Liver metastatic tumours of the mice were used for liver weight measures and H&E staining. Immunofluorescence was applied to observe the infiltration of TAMs, the expression of neutral sphingomyelinase 2 (nSMase2) and Rab27a. Results: By screening our TCM monomer library, we found that ASIV, which is mainly extracted from Radix Astragali, reduced the release of TEVs from CRC cells in a time- and concentration-dependent manner. Mechanistically, ASIV inhibited the production and secretion of TEVs by downregulating nSMase2 and Rab27a expression in CRC cells. CM from ASIV-treated CRC cells reshaped the polarization of TAMs by decreasing M2-type polarization, increasing M1-type polarization. Consequently, the repolarization of M2-type to M1-type macrophages led to reduced invasion and migration of CRC cells. Moreover, we confirmed that ASIV inhibited the liver metastasis of CRC, reduced M2-type macrophage infiltration and decreased the expression of nSMase2 and Rab27a in liver metastases. Conclusions: ASIV inhibited CRC metastasis by reducing EVs release and suppressing M2-type TAMs activation. All these findings reveal a new insight into the mechanisms of ASIV in preventing CRC progression and provide a promising approach for anti-tumour therapy.

Management of Acquired Uterine Arteriovenous Malformations Associated with Retained Products of Conception.

PURPOSE: To evaluate the efficacy and safety of different treatments for acquired uterine arteriovenous malformations associated with retained products of conception (UAVM-RPOC) and to investigate the role of uterine artery embolization (UAE) in acquired UAVM-RPOC. MATERIALS AND METHODS: This was a retrospective study of consecutive patients who were diagnosed with uterine arteriovenous malformation by ultrasound after recently terminated pregnancy. Forty-eight patients were included in this study and were divided into 2 groups (major and minor bleeding groups) according to vaginal bleeding. The treatments were analyzed between groups. Technical and clinical success rates of UAE were analyzed. RESULTS: Of the 48 patients, 11 patients were in the massive bleeding group and 37 were in the minor bleeding group. Five patients were referred for UAE in each group and UAE was a priority for patients with unstable hemodynamics (chi-square value = 5.524, P =.022). Conservative management, dilation and curettage (D&C), operative hysteroscopy, and UAE were performed in 16 (33%), 18 (38%), 7 (15%), and 13 (27%) patients, respectively. Two patients with ectopic pregnancies suffered uncontrollable bleeding during D&C and required emergent UAE. Three patients underwent UAE before surgery to prevent hemorrhage. The technical and clinical success rates of UAE were 100%. No complications or recurrences occurred. CONCLUSIONS: UAE is a safe and effective treatment for UAVM-RPOC and a priority for patients with unstable hemodynamics. Conservative management, D&C, and hysteroscopy are safe and effective for patients with UAVM-RPOC with stable hemodynamics. However, UAVM-RPOC following ectopic pregnancy may have high risks of massive hemorrhage during procedures.

[Analysis of risk factors for preoperative mechanical ventilation in patients with acute traumatic cervical spinal cord injury].

OBJECTIVE: To analyze the risk factors associated with mechanical ventilation before surgery in patients with acute traumatic cervical spinal cord injury(TCSCI). METHODS: According to whether preoperative mechanical ventilation, 59 patients with TCSCI admitted to our hospital from November 2016 to May 2018 were divided into mechanical ventilation(MV)group (37 cases) and non-mechanical ventilation(non-MV) group (22 cases). Falling from height was the most common causes of injury(30 cases, 50.8%), then was traffic accident(22 cases, 37.3%). The most common paraplegic plane was in C1-C4(36 cases, 61%). American Spinal Cord Injury Association(ASIA) injury degree and ASIA exercise score(AMS) were used to assess the extent of affected neurological plane and spinal cord injury. Trauma severity score(ISS) was used to evaluate the severity of the injury. Multivariate Logistic regression was used to analyze the risk factors for mechanical ventilation in TCSCI. ROC curves were used to assess the value of AMS and ISS in predicting mechanical ventilation. RESULTS: Univariate analysis showed that the percentage of male, complete injury and related injuries in the MV group were significantly higher than those in the non-MV group(P<0.05). The AMS score of the MV group was significantly lower than that of the non-MV group (16.4±10.7 vs 39.1±9.5, P<0.001), and the ISS score was significantly higher than that of the non-MV group(31.6±8.0 vs 26.5±6.7, P=0.015). Multivariate Logistic regression analysis showed that AMS[OR=3.340, 95% CI(1.321, 6.242), P<0.001] and ISS [OR=1.120, 95% CI(0.306, 3.786), P<0.001] were significant risk factors on predicting the need for mechanical ventilation.The ROC analysis showed that the area under the ROC curve(AUC) of AMS was significantly higher than that of ISS(0.899 vs 0.685, P<0.05). CONCLUSIONS: AMS and ISS at admission can be used as predictors of early mechanically assisted ventilation.

[Anterior surgery for fourth lumbar burst fractures].

OBJECTIVE: To evaluate the clinical outcomes of anterior decompression, bone graft and internal fixation in treating fourth lumbar burst fractures with iliac fenestration. METHODS: From February 2001 to May 2006, 8 cases of fourth lumbar burst fractures were treated by anterior decompression, correction, reduction, iliac autograft, Z-plate internal fixation with-iliac fenestration. Of them, there were 7 males and 1 female, aging 24-46 years with an average of 29.3 years, including 3 cases of Denis type A and 5 cases of Denis type B. The decompression, intervertebral height were compared between preoperation and postoperation by CT scanning. According to Frankel assessment for neurological status, 2 cases were at grade C, 5 at grade D and 1 at grade E before operation. Four cases had different degrees of disturbance of sphincter. Time from injury to operation was 8 hours to 11 days. The preoperative height of the anterior border of the L4 vertebral body was (13.8 +/- 2.3) mm, the Cobb angel of fractured vertebral body was (13.2 +/- 2.5) degrees, the vertebral canal sagittal diameter of L4 was (10.6 +/- 3.5) mm. The bone graft volume was (7.5 +/- 1.3) cm3 during operation. RESULTS: Operations were performed successfully. The mean operative time was (142 +/- 25) minutes and the mean amount of blood loss was (436 +/- 39) mL. The incisions obtained healing by first intention after operation. Two cases suffered donor site pain and received no treatment. The follow-up time of 8 cases was from 21 months to 52 months (mean 24.5 months). At one week after operation, the height of the anterior border of the L4 vertebral body was (32.5 +/- 2.6) mm, the Cobb angel of fractured vertebral body was (6.8 +/- 3.7) degrees, and the vertebral canal sagittal diameter of L4 was (19.8 +/- 5.1) mm, showing significant difference when compared with those of preoperation (P < 0.01). At the final follow-up, the results showed that the pressure was reduced sufficiently, all autograft fused well, the neurological status improved at Frankel grade from C to D in 1 patient, from D to E in 3 patients, but the others had no improvement. In 4 patients who had disturbance of sphincter, 3 restored to normal and 1 was better off. CONCLUSION: Clinical outcomes of anterior surgery for fourth lumbar burst fractures with iliac fenestration are satisfactory. It can facilitate operation, reduce the pressure sufficiently, maintenance intervertebral height and recover the neurological function.