Objective To explore a safe dose range of spinal IMRT by comparing the cell damage in Beagles at different dose levels.Methods Thirty Beagles were randomly divided into 5 groups.The Beagle clinical model of tumor was established in the ninth and tenth thoracic spine.The Beagles were subjected to IMRT with the total doses of 0,40,50,60,70 Gy,respectively.The samples of spine were taken out from the same locum of the ninth and tenth thoracic spine at 3 month after radiation.All the samples were observed by the hematoxylin-eosin staining,and the VEGF expression in spine was evaluated by immunohistochemistry.Terminal deoxynucleatidyl transferase mediated dUTP nick and labeling (TUNEL) technique was used to examine the apoptotic cells in the spine.Results The osteocytes in the spine showed reversible injury in 40 Gy group,and cell apoptosis in 50,60,70 Gy groups.Compared with 40 Gy group,the rates of lacuna were increased in 50,60,70 Gy groups(F =2.57,P ＜0.05),as well as the cell apoptotic rates(F =3.52,P ＜ 0.05) and the expression of VEGF (F =3.64,P ＜ 0.05),but there were no significant differences among 50,60,70 Gy groups (P ＞ 0.05).Conclusions The late radiotherapy response of the spine was obviously observed at 3 month after radiation,especially at 50 Gy.

Objective To explore the effect of intracavitary therapy on acute pulmonary embohsm.Methods Fifteen patients were selected as our subjects,who suffered acute pulmonary embolism and received percutaneous catheter thrombus crashing and catheter directed thrombolysis in Beijing Military.Region General Hospital from January 2009 to June 2011.Local injection of Urokinase was performed with a total amount of 500 000 U in catheter directed thrombolysis.After thrombolysis,low molecular Heparin was administered to patients for 7-10 days and oral administration of Warfarin was performed for 3-6 months.Clinical symptoms,improvement of physical signs,complications,changes of mean pulmonary arterial pressure(mPAP) and arterial partial pressure of oxygen(PO2),and the opening of pulmonary artery were recorded.Results The pulmonary arteries of the 12 patients were completely opened,and partially opened in 3 patients.The effective rate was 100％ (15/15).mPAP was reduced from (40.07 ±5.97) mmHg to (20.00 ±4.66) mmHg (t =-1.128,P ＜ 0.05),PO2 was increased from (50.26 ± 9.30) mmHg to (80.49 ± 9.04) mmHg (t =1.246,P ＜ 0.05).Patients were followed-up for 3-6 months and no recurrence case was seen.Conclusion The interventional therapy is effective,safe and practicable in the treatment of acute pulmonary embolism.

Objective Proximal humerus fracture is the most common upper-arm osteoporotic fracture in elderly patients and the result of treatment directly affects the physiological function of the shoulder .This article discusses the clinical effect of the locking proximal humeral plate ( LPHP) combined with anti-osteoporosis drugs in the treatment of osteoporotic comminuted proximal humerus fractures in elderly patients . Methods This study included of 47 elderly osteoporotic patients with comminuted proximal humerus fractures treated from April 2009 to March 2012 and with complete follow-up data.According to the Neer classification , the patients were divided into groups A (LPHP treatment, n=23, including 13 cases of three-part fractures and 10 cases of four-part fractures) and B (LPHP+anti-osteoporosis drugs, n=24, including 13 cases of three-part fractures and 11 cases of four-part fractures). Results All the patients were followed up for 14 to 38 (mean 23.6) months.The postoperative healing time was significantly shorter in group B than in group A ([96.57 ±2.59]d vs [115.91 ±2.73]d, P<0.05), and the excellence rate was remarkably higher in B than in A (91.7%vs 78.3%,P<0.05). Conclusion With the advantages of short healing time and high excellence rate , LPHP+anti-os-teoporosis drugs is superior to simple LPHP in the treatment of osteoporotic comminuted proximal humerus fractures in elderly patients.

Objective By using quantum dots-based double-color imaging method to simultaneously label human epidermal growth factor 2 (HER2) on breast cancer cell membrane and the type Ⅳ collagen in the extracellular matrix.To monitor the degree of malignancy of breast cancer and the invasive and metastatic potential.Methods The co-expressions of HER2 and the type Ⅳ collagen in breast cancer of 54 cases were detected and quantified by quantum dots-based double-labeling immunofluorescent histochemistry,and its correlation with clinical pathology parameters and prognosis were analyzed.Results With the increasing HER2 expression level,a progressive decrease in collagen Ⅳ around the cancer nest,the expression of HER2 and the type Ⅳ collagen value was negatively correlated (r =-0.980,P ＜ 0.05) ; the expression of HER2 and collagen Ⅳ was associated with lymph note metastasis,pathological stage (TNM) and disease-free survival(P ＜ 0.05).The expression of HER2 and the type Ⅳ collagen between different age groups,menopause and estrogen receptor (ER) and progesterone receptor (PR) were not significantly different (P ＞ 0.05).Conclusions Quantum dots-based double-color imaging method provides direct observable evidence to support the degradation of HER2 and the type Ⅳ collagen expression,which may help in determining the degree of malignancy and evaluating prognosis.

BACKGROUND:The unstable distal radius fractures are clinical y treated with external fixation, open reduction and internal fixation at present. These two methods have their advantages and disadvantages. OBJECTIVE:To compare the radiological, clinical and functional outcomes of two groups of patients treated by bridging external fixation combined with Kirschner wire fixation versus volar locked plate for a displaced fracture of the distal radius. METHODS:We col ected 68 cases of unstable distal radius fractures in the Department of Reparative and Reconstructive Surgery, First Affiliated Hospital of Xinjiang Medical University, China from October 2014 to April 2016. They were randomly assigned to two groups, with 34 in each group. Patients in the external fixation group received external fixator and Kirschner wire. Patients in the internal fixation group received volar locked plate. In the fol ow-up, outcomes were assessed by radiographic parameters, function parameters, and Cooney functional score between both groups. RESULTS AND CONCLUSION:(1) Al patients were fol owed up. External fixation group was fol owed up for 12-16 months. Internal fixation group was fol owed up for 13-15 months. X-rays showed al fractures healed. (2) At 3 months postoperatively, significant differences in pronation, supination, extension and radial deviation were detected between the two groups (P<0.05), and the internal fixation had more advantages. At 6 months, these differences had become reduced. The extension of the wrist and pronation were stil better in the internal fixation group. However, there was no significant difference between the two groups between preoperatively and 12 months postoperatively (P>0.05). The range of motion of the wrist was better in the internal fixation group, but no significant difference in the grip strength was determined between the two groups at any time points in 1-year fol ow-up. (3) These results demonstrated that compared with the external fixation, volar locked plate fixation showed better early recovery postoperatively. With time prolonged, clinical outcomes of both repair methods tended to be consistent.

Objective:To summarize the experience of Bacillus Calmette-Guerin(BCG) in the treatment of bladder cancer secondary to renal transplantation.Methods:The clinical data of 5 patients who underwent BCG bladder irrigation after secondary bladder cancer after kidney transplantation in Tianjin First Central Hospital from January 2015 to December 2019 were analyzed. There were 1 male and 4 female cases. During the period of immunosuppression after transplantation, 1 case developed secondary high-level non-muscular invasive bladder cancer (NMIBC), 3 cases developed secondary low-grade NMIBC, and 1 case developed secondary glandular cystitis (4 cases). The mean age of the 5 patients with secondary bladder cancer was 59.7±4.0 years. Case one with high level NMIBC was treated with transurethral resection of bladder tumor (TURBT) and postoperative irrigation of epirubicin. Case 3 and 5 with low-level NMIBC accepted regular postoperative irrigation of gemcitabine. No irrigative therapy was performed in case 2. Bladder cancer recurred in case 1, 2, 3 and 5 after 20.1±9.7 months. TURBT was observed in all the 4 patients, among which 3 were of high grade NMIBC and 1 was of low grade NMIBC. Four patients were irrigated with BCG 2 weeks after operation. Postoperative pathology indicated low-level NMIBC in case 4, and BCG was irrigated 2 weeks after the operation. During perfusion therapy, immunosuppressive agents were continued.Results:During BCG perfusion, 4 of the 5 cases showed BCG related local inflammation, among which 2 cases presented symptoms of bladder irritation, 1 case presented hematuria, and 1 case presented hematuria with low fever. Patients with frequent urination, pain in urine, hematuria and other symptoms improved after drinking plenty of water, taking bed rest and taking levofloxacin (0.5g/ day ×7 days). Patients with low fever were treated with antipyretic treatment. No antituberculous agents were used prophylactically during BCG perfusion. There were no symptoms of tuberculosis infection or sepsis. The function of transplantated kidney was normal and no tendency of rejection. The 5 patients were followed up for 7-24 months, 1 patient was lost to follow-up after 7 months of BCG bladder perfusion, and no tumor recurrence or metastasis was found in 5 patients during the follow-up.Conclusions:The use of immunosuppressive agents does not reduce the biological activity of BCG, and BCG does not increase the risk of systemic toxicity or affect the function of transplanted kidneys in immunocompromised patients. BCG is a treatment option for bladder cancer secondary to renal transplantation.

OBJECTIVE: To investigate whether the acetaldehyde dehydrogenase 2 specific activator, Alda-1, can alleviate brain injury after cardiopulmonary resuscitation (CPR) by inhibiting cell ferroptosis mediated by acyl-CoA synthetase long-chain family member 4/glutathione peroxidase 4 (ACSL4/GPx4) pathway in swine. METHODS: Twenty-two conventional healthy male white swine were divided into Sham group (n = 6), CPR model group (n = 8), and Alda-1 intervention group (CPR+Alda-1 group, n = 8) using a random number table. The swine model of CPR was reproduced by 8 minutes of cardiac arrest induced by ventricular fibrillation through electrical stimulation in the right ventricle followed by 8 minutes of CPR. The Sham group only experienced general preparation. A dose of 0.88 mg/kg of Alda-1 was intravenously injected at 5 minutes after resuscitation in the CPR+Alda-1 group. The same volume of saline was infused in the Sham and CPR model groups. Blood samples were collected from the femoral vein before modeling and 1, 2, 4, 24 hours after resuscitation, and the serum levels of neuron specific enolase (NSE) and S100 β protein were determined by enzyme-linked immunosorbent assay (ELISA). At 24 hours after resuscitation, the status of neurologic function was evaluated by neurological deficit score (NDS). Thereafter, the animals were sacrificed, and brain cortex was harvested to measure iron deposition by Prussian blue staining, malondialdehyde (MDA) and glutathione (GSH) contents by colorimetry, and ACSL4 and GPx4 protein expressions by Western blotting. RESULTS: Compared with the Sham group, the serum levels of NSE and S100β after resuscitation were gradually increased over time, and the NDS score was significantly increased, brain cortical iron deposition and MDA content were significantly increased, GSH content and GPx4 protein expression in brain cortical were significantly decreased, and ACSL4 protein expression was significantly increased at 24 hours after resuscitation in the CPR model and CPR+Alda-1 groups, which indicated that cell ferroptosis occurred in the brain cortex, and the ACSL4/GPx4 pathway participated in this process of cell ferroptosis. Compared with the CPR model group, the serum levels of NSE and S100 β starting 2 hours after resuscitation were significantly decreased in the CPR+Alda-1 group [NSE (μg/L): 24.1±2.4 vs. 28.2±2.1, S100 β (ng/L): 2 279±169 vs. 2 620±241, both P < 0.05]; at 24 hours after resuscitation, the NDS score and brain cortical iron deposition and MDA content were significantly decreased [NDS score: 120±44 vs. 207±68, iron deposition: (2.61±0.36)% vs. (6.31±1.66)%, MDA (μmol/g): 2.93±0.30 vs. 3.68±0.29, all P < 0.05], brain cortical GSH content and GPx4 expression in brain cortical was significantly increased [GSH (mg/g): 4.59±0.63 vs. 3.51±0.56, GPx4 protein (GPx4/GAPDH): 0.54±0.14 vs. 0.21±0.08, both P < 0.05], and ACSL4 protein expression was significantly decreased (ACSL4/GAPDH: 0.46±0.08 vs. 0.85±0.13, P < 0.05), which indicated that Alda-1 might alleviate brain cortical cell ferroptosis through regulating ACSL4/GPx4 pathway. CONCLUSIONS Alda-1 can reduce brain injury after CPR in swine, which may be related to the inhibition of ACSL4/GPx4 pathway mediated ferroptosis.
Male ; Animals ; Swine ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Ferroptosis ; Brain Injuries ; Glutathione ; Cardiopulmonary Resuscitation ; Ligases ; Iron

BACKGROUND:The surgical method for the treatment of unstable distal radius fracture mainly includes plate internal fixation and external fixator, but both of these two methods have the advantages and disadvantages. Which treatment is more conducive to the rehabilitation of patients, there is stil controversy.
OBJECTIVE:To evaluate the clinical effectiveness of internal fixation and external fixator for the treatment of unstable distal radius fractures.
METHODS:The relative databases and literatures were searched with the computer and hand to col ect the randomized control ed trials of internal fixation versus external fixator for the treatment of unstable distal radius fractures. After extraction literature data and quality evaluation, RevMan 5.2 software was used for system evaluation. The grip strength, disabilities of arm, shoulder&hand score, complications rates, infection rates, deformity rates and ulnar variance rates were compared between two groups.
RESULTS AND CONCLUSION:A total of 9 literatures, involving total y 524 patients were included, 286 patients in the internal fixation group and 238 patients in the external fixator group. There was no significant difference in grip strength between internal fixation group and the external fixator group. The results of Meta-analysis showed that the internal fixation group was better than the external fixator group in the aspects of disabilities of arm, shoulder&hand score, complications rate, infection rate, deformity rate and ulnar variance rate at 3 months and 1 year after treatment. The results indicate that the plate internal fixation is better than external fixator in the treatment of unstable distal radius fractures, but the large sample, double-blind, and high quality randomized control ed trials are stil needed to identify the results.

Objective:To evaluate the effect of Alda-1 on ferroptosis in cardiomyocytes after cardiac arrest and cardiopulmonary resuscitation in swine.Methods:Twenty-two healthy male white swine, weighing 35-43 kg, were divided into 3 groups using a random number table method: sham operation group (group S, n=6), cardiac arrest-cardiopulmonary resuscitation group (group CA-CPR, n=8) and Alda-1 group ( n=8). The animals only underwent the general preparation in group S, and the swine model of cardiac arrest and cardiopulmonary resuscitation was developed by 8 min of electrically induced cardiac arrest through the pacing catheter in the right ventricle followed by 8 min of cardiopulmonary resuscitation in CA-CPR and Alda-1 groups.Alda-1 0.88 mg/kg was intravenously injected at 5 min after resuscitation in group Alda-1, and the equal volume of vehicle was administered instead in the other two groups.Stroke volume (SV) and global ejection fraction (GEF) were measured using PiCCO before developing the model and at 1, 2 and 4 h after resuscitation (T 0-3). Venous blood samples were collected from the femoral vein to measure the concentrations of serum cardiac troponin (cTnI) by enzyme-linked immunosorbent assay at T 0-3, and at 24 h after resuscitation (T 4). The animals were then sacrificed, and myocardial tissues in the left ventricle were harvested to measure the expression of acyl-CoA synthetase long-chain family member 4 (ACSL4) and glutathione peroxidase 4 (GPX4) (by Western blot), iron deposition (by Prussian blue staining), 4-hydroxy-2-nonenal (4-HNE) content (by enzyme-linked immunosorbent assay), and malondialdehyde (MDA) and glutathione (GSH) contents (by colorimetry). Results:Compared with group S, SV and GEF were significantly decreased at T 1-3, the serum concentrations of cTnI were increased at T 1-4, myocardial ACSL4 expression was up-regulated, GPX4 expression was down-regulated, iron deposition and contents of 4-HNE and MDA were increased, and the content of GSH was decreased in CA-CPR and Alda-1 groups ( P<0.05). Compared with group CA-CPR, SV and GEF were significantly increased at T 2-3, the serum concentrations of cTnI were decreased at T 3-4, myocardial ACSL4 expression was down-regulated, GPX4 expression was up-regulated, iron deposition and contents of 4-HNE and MDA were decreased, and the content of GSH was increased in group Alda-1 ( P<0.05). Conclusions:Alda-1 can alleviate myocardial injury after cardiac arrest and cardiopulmonary resuscitation in swine and further improve cardiac dysfunction, and the mechanism may be related to inhibition of cell ferroptosis.

Objective:To explore the role and mechanism of tubastatin A (TubA) in alleviating brain injury after cardiac arrest and cardiopulmonary resuscitation (CA-CPR) by inhibiting endoplasmic reticulum stress-mediated cell apoptosis in swine.Methods:Twenty-three conventional male white swine, weighing 33-40 kg, aged 4 to 6 months, were divided into 3 groups by random number table method: sham group ( n=6), CA-CPR group ( n=9), and TubA group ( n=8). The CA-CPR swine model was established by 9 min of electrically induced CA through pacing catheter in the right ventricle and then 6 min of CPR in the CA-CPR group. The CA-CPR swine model was established by the same method, and then a dose of 4.5 mg/kg of TubA at 5 min after resuscitation was intravenously infused in the TubA group. The serum concentrations of neuron specific enolase (NSE) and S100β protein (S100β) were measured using ELISA before modeling and at 1, 2, 4 and 24 h after resuscitation. Neurological deficit score (NDS) was evaluated at 24 h after resuscitation. Thereafter, the animals were euthanized, and brain cortex tissues were harvested, and the expression levels of caspase-12 and caspase-3 were measured using immunohistochemistry. Cell apoptosis index was detected by TUNEL assay. The variables among the three groups were compared with one-way analysis of variance and the Bonferroni hoc test using SPSS software. Results:Twenty-four h after resuscitation, the serum concentrations of NSE and S100β were significantly increased, and NDS was markedly elevated in the CA-CPR and TubA groups compared with the sham group (all P<0.05). Compared with the CA-CPR group, serum concentration of NSE starting 2 h after resuscitation and serum concentration of S100β starting 1 h after resuscitation were significantly decreased in the TubA group [NSE (ng/mL): (23.1±2.0) vs. (20.2±2.0) at 2 h, (28.4±2.3) vs. (23.7±1.9) at 4 h, (32.1±2.7) vs. (26.6±2.0) at 24 h; S100β (pg/mL): (2239±193) vs. (1923±101) at 1 h, (2817±157) vs. (2360±141) at 2 h, (3384±250) vs. (2691±210) at 4 h, (3965±303) vs. (3119±260) at 24 h, all P<0.05], and NDS was markedly reduced (240±30 vs. 63±44, P<0.05). At 24 h after resuscitation, brain cortex tissue detection showed that the expression levels of caspase-12 and caspase-3 were significantly increased, and cell apoptosis index was markedly elevated in the CA-CPR and TubA groups compared with the sham group (all P<0.05). However, the expression levels of caspase-12 and caspase-3 were significantly decreased [caspase-12:(7.1±0.7) vs. (4.2±0.4); caspase-3: (13.3±1.6) vs. (7.7±0.8), all P<0.05], and cell apoptosis index was markedly reduced in the TubA group compared to the CA-CPR group [(31.1±8.6) vs. (17.3±2.2), P<0.05]. Conclusions:TubA alleviates brain injury and neurological dysfunction after CA-CPR in swine, which may be related to the inhibition of cell apoptosis mediated by endoplasmic reticulum stress.