Cerebrovascular remodeling is the most important pathologic change during hypertension. Stroke induced by hypertension is threatening thousands of people's lives. The ion channels in cerebrovascular smooth muscle cells may be altered during hypertension and thus the abnormality of cytosolic ion concentration can accelerate cerebrovascular remodeling. These channels, including potassium channels, calcium channels and chloride channels, may play an important role in the cerebrovascular remodeling during hypertension.

Objective To study the protective effect of Res o n myocardial ischemic/reperfused induced injury. Methods My ocardial ischemic/reperfusion model was used to study the protective effect of d ifferent dosage resvaratrol on myocardial ischemic/reperfusion injury in rats. Results Res shrinked the size of myocardial infarction indu ced by the ischemic reperfused method, inhibited the release of creatine kinase( CK) and lactate dehydrogenase(LDH) from the injured myocardium and reduced elega ted ST-T of electrocardiogram(ECG) caused by myocardial ischemic-reperfused in jury in dose-dependent way. Res also improved the morphological changes of inju red myocardium. Conclusion Res has protective action on myo cardial ischemic reperfused injury in rats.

Objective To investigate the therapeutic effect of VSD combined with external fixator in the treatment of open tibial and fibular fractures in Tibet plateau. Methods From August 2014 to August 2015, totally 16 cases of open tibial and fibular fractures were treated in our department, including 12 males and 4 females with an average 39. 4 years-old. There were 4 cases of proximal and mid tibial fractures while 12 cases were distal fractures. Debridement, vacuum sealing drainage combined with external fixator for stabilization of fractures was performed in all patients after general condition was improved. A vacuum sealing drainage change or second stage wound closure or soft tissue coverage was undergone after 7 days. Bone union time by X-ray and complications were recorded. Results All wounds were healed by second stage. Twelve patients months were followed up ( by calling back to the hospital ) for an average 18 months ( 12 to 24 months ) , 4 cases were lost to follow-up. X-ray demonstrated that bone union was obtained at a mean 5. 5th month (3 to 7 months). There were 9 cases (75%) obtained a first phase of fracture healing, while 3 cases ( 25%) of delayed healing. Pin-track infection was occurred in two patients and was cured by conservative treatment. No complications of deep infection, graft skin or flap necrosis, malunion, nonunion or osteomyelitis was seen during follow-up. Conclusions Vacuum sealing drainage combined with external fixator for treatment of open tibial and fibular fracture in Tibet can rapidly and effectively stabilize the fracture, and simultaneously safely and effectively seal the wound, reduce the wound healing time, promote fracture healing and lower the complication rates.

Objective To explore the clinical effect of mechanical perfusion for preserving kidney.Methods From May to October 2013, 36 donors’ kidneys were preserved by mechanical perfusion in the Department of Kidney in the 181st Hospital of Chinese People's Liberation Army.The donors’ kidneys were preserved , transported and perfused by the LKT-100 type Lifeport organ transporter and special software.General condition of patients and the relationship between resistance coefficient , flow velocity and occurrence of delayed graft function ( DGF) were analyzed.Results None of 36 recipients had graft loss.Thirty cases ’ (83%) renal function recovered well without DGF.Six cases developed DGF and returned to normal gradually after 3-18 days postoperative treatment.After mechanical renal perfusion for 1 h, 28 recipients with kidneys ’ resistance coefficient ≤0.3 mmHg/( ml · min ) hadn't developed DGF after transplantation.Among 8 recipients with kidneys ’ resistance coefficient >0.3 mmHg/( ml · min ) , 6 recipients developed DGF.Eight recipients with kidneys ’ flow velocity >100 ml/min hadn't developed DGF.Among 21 recipients with kidneys ’ flow velocity 60-100 ml/min, 1 case developed DGF.In 7 recipients with kidneys ’ flow velocity <60 ml/min, 5 cases developed DGF.Conclusions Mechanical perfusion for preserving kidney can improve graft quality and reduce the incidence of DGF in recipients.

OBJECTIVE: To screen for small molecular compounds with selective inhibitory activity against cutaneous melanoma cells with BAP1 deletion. METHODS: Cutaneous melanoma cells expressing wild-type BAP1 were selected to construct a BAP1 knockout cell model using CRISPR-Cas9 system, and small molecules with selective inhibitory activity against BAP1 knockout cells were screened from a compound library using MTT assay. Rescue experiment was carried out to determine whether the sensitivity of BAP1 knockout cells to the candidate compounds was directly related to BAP1 deletion. The effects of the candidate compounds on cell cycle and apoptosis were detected with flow cytometry, and the protein expressions in the cells were analyzed with Western blotting. RESULTS: The p53 activator RITA from the compound library was shown to selectively inhibit the viability of BAP1 knockout cells. Overexpression of wild-type BAP1 reversed the sensitivity of BAP1 knockout cells to RITA, while overexpression of the mutant BAP1 (C91S) with inactivated ubiquitinase did not produce any rescue effect. Compared with the control cells expressing wild-type BAP1, BAP1 knockout cells were more sensitive to RITA-induced cell cycle arrest and apoptosis (P < 0.0001) and showed an increased expression of p53 protein, which was further increased by RITA treatment (P < 0.0001). CONCLUSION Loss of BAP1 results in the sensitivity of cutaneous melanoma cells to p53 activator RITA. In melanoma cells, the activity of ubiquitinase in BAP1 is directly related to their sensitivity to RITA. An increased expression of p53 protein induced by BAP1 knockout is probably a key reason for RITA sensitivity of melanoma cells, suggesting the potential of RITA as a targeted therapeutic agent for cutaneous melanoma carrying BAP1-inactivating mutations.
Humans ; Melanoma ; Skin Neoplasms ; Tumor Suppressor Protein p53 ; Apoptosis ; Cell Division ; Tumor Suppressor Proteins/genetics* ; Ubiquitin Thiolesterase/genetics*