Fasudil prevents liver fibrosis via activating natural killer cells and suppressing hepatic stellate cells.

BACKGROUND: Fasudil, as a Ras homology family member A (RhoA) kinase inhibitor, is used to improve brain microcirculation and promote nerve regeneration clinically. Increasing evidence shows that Rho-kinase inhibition could improve liver fibrosis. AIM: To evaluate the anti-fibrotic effects of Fasudil in a mouse model of liver fibrosis induced by thioacetamide (TAA). METHODS: C57BL/6 mice were administered TAA once every 3 d for 12 times. At 1 wk after induction with TAA, Fasudil was intraperitoneally injected once a day for 3 wk, followed by hematoxylin and eosin staining, sirius red staining, western blotting, and quantitative polymerase chain reaction (qPCR), and immune cell activation was assayed by fluorescence-activated cell sorting. Furthermore, the effects of Fasudil on hepatic stellate cells and natural killer (NK) cells were assayed in vitro. RESULTS: First, we found that TAA-induced liver injury was protected, and the positive area of sirius red staining and type I collagen deposition were significantly decreased by Fasudil treatment. Furthermore, western blot and qPCR assays showed that the levels of alpha smooth muscle actin (α-SMA), matrix metalloproteinase 2 (MMP-2), MMP-9, and transforming growth factor beta 1 (TGF-ß1) were inhibited by Fasudil. Moreover, flow cytometry analysis revealed that NK cells were activated by Fasudil treatment in vivo and in vitro. Furthermore, Fasudil directly promoted the apoptosis and inhibited the proliferation of hepatic stellate cells by decreasing α-SMA and TGF-ß1. CONCLUSION: Fasudil inhibits liver fibrosis by activating NK cells and blocking hepatic stellate cell activation, thereby providing a feasible solution for the clinical treatment of liver fibrosis.

Iliac ecchymosis, a valuable sign for hollow viscus injuries in blunt pelvic trauma patients.

PURPOSE: Pelvic fractures are characterized by high energy injuries and often accompanied with abdominal and pelvic organ injury. CT has been applied for several decades to evaluate blunt pelvic trauma patients. However, it has a certain rate of inaccurate diagnosis of abdominal hollow viscus injury (HVI), especially in the early stage after injury. The delayed diagnosis of HVI could result in a high morbidity and mortality. The bowel injury prediction score (BIPS) applied 3 clinical variables to determine whether an early surgical intervention for blunt HVI was necessary. We recently found another clinical variable (iliac ecchymosis, IE) which appeared at the early stage of injury, could be predicted for HVI. The main objective of this study was to explore the novel combination of IE and BIPS to enhance the early diagnosis rate of HVI, and thus reduce complications and mortalities. METHODS: We conducted a retrospective analysis from January 2008 to December 2018 and recorded blunt pelvic trauma patients in our hospital. The inclusion criteria were patients who were verified with pelvic fractures using abdomen and pelvis CT scan in the emergency department before any surgical intervention. The exclusion criteria were abdominal CT insufficiency before operation, abdominal surgery before CT scan, and CT mesenteric injury grade being 5. The MBIPS was defined as BIPS plus IE, which was calculated according to 4 variables: white blood cell counts of 17.0 or greater, abdominal tenderness, CT scan grade for mesenteric injury of 4 or higher, and the location of IE. Each clinical variable counted 1 score, totally 4 scores. The location and severity of IE was also noted. RESULTS: In total, 635 cases were hospitalized and 62 patients were enrolled in this study. Of these included patients, 77.4% (40 males and 8 females) were operated by exploratory laparotomy and 22.6% (8 males and 6 females) were treated conservatively. In the 48 patients underwent surgical intervention, 46 were confirmed with HVI (45 with IE and 1 without IE). In 46 patients confirmed without HVI, only 3 patients had IE and the rest had no IE. The sensitivity and specificity of IE in predicting HVI was calculated as 97.8% (45/46) and 81.3% (13/16), respectively. The median MBIPS score for surgery group was 2, while 0 for the conservative treatment group. The incidence of HVI in patients with MBIPS score ≥ 2 was significantly higher than that in patients with MBIPS score less than ≤ 2 (OR = 17.3, p < 0.001). CONCLUSION: IE can be recognized as an indirect sign of HVI because of the high sensitivity and specificity, which is a valuable sign for HVI in blunt pelvic trauma patients. MBIPS can be used to predict HVI in blunt pelvic trauma patients. When the MBIPS score is ≥ 2, HVI is strongly suggested.

[Prognostic correlation of intracranial pressure monitoring in patients with severe craniocerebral injury].

OBJECTIVE: To explore the clinical application of intracranial pressure (ICP) monitoring and its prognostic correlation in patients with severe craniocerebral injury. METHODS: A total of 216 severe craniocerebral injury patients with scores of Glasgow coma scale 3-8 underwent craniotomy at Affiliated Qilu Hospital, Shandong University.And 168 cases of ICP monitoring were divided into 3 treatment groups and another 48 cases without ICP monitoring selected as the control group.According to ICP, stepwise treatment was administered to control the level of ICP and maintain the cerebral perfusion pressure to analyze the relationship between ICP monitoring and prognosis. RESULTS: As compared with the control group, there were significant decreases of disability and mortality rate for patients with ICP monitoring (A, B, C group). Especially group C had a better prognosis than the other groups for statistical significance.In addition, the dose and duration of mannitol of group A, B or C were significantly lower than those of the control group (P < 0.05). CONCLUSION: The application of ICP monitoring is capable of reducing mortality, improving prognosis and enhancing success rate of treating severe craniocerebral injury.

Functional and structural recovery of injured spinal cord following delayed X-irradiation in rats.

OBJECTIVE: To test the hypothesis that delayed X-irradiation can enhance the functional and structural recovery of the injured spinal cord in rats. METHODS: Seventy Sprague-Dawley rats were randomly divided into two groups, 35 rats in each. The control group sustained a one-minute clip compression (force of clip was 30 g) injury of the spinal cord at the T2 level, without X-irradiation. The experimental group received X-irradiation 14 days after injury. Neurological function was assessed by the modified Tarlov method, including hind limbs movement, inclined plane, and pain withdrawal. These tests were performed in a blinded fashion at 3, 7, 14, 21, 28, 35, and 42 days after injury. At 43 days after injury, histological examination of the injured spinal cord was performed following decapitation of the rats. RESULTS: Sixty-two rats met the experimental requirements (spinal cord injury was similar), 32 rats in experimental group and 30 rats in control group. Statistically significant difference was observed between the two groups in hind limbs movement and inclined plane (P < 0.01), but not in the pain withdrawal test. The edema and necrosis areas of injured spinal cords in experimental group were less than those in control group, and axons in experimental group were significantly more than those in control group (P < 0.01). CONCLUSION: Delayed X-irradiation following spinal cord injury may enhance functional recovery by improving and restoring structural integrity of the injured spinal cord in rats.