Screening of a novel CRM1 targeting inhibitor and its effects on the proliferation and growth of extranodal NK/T cell lymphoma / 中国药科大学学报

@#The purpose of this study was to screen out the novel chromosome maintenance protein 1(CRM1)covalent targeting inhibitors by computer-assisted drug design(CADD), and to study their effects on the proliferation of extranodal nature killer/T cell lymphoma(ENKTL). A novel CRM1 inhibitor LFS-829 was designed based on the molecular structure of LFS-01 by means of ADME/T and covalent docking. The target binding of LFS-829 with CRM1 was analyzed by MALDI-TOF mass spectrometry. The effects of LFS-829 on the proliferation of extranodal NK/T cell lymphoma SNK6 and HANK-1 cells were detected by CCK-8. The cell morphology was observed by live cell workstation. Immunofluorescence experiments were used to analyze the effect of LFS-829 on nuclear export function of CRM1. The changes of NF-κB signaling pathway under different concentrations of LFS-829 were analyzed by Western blot, dual luciferase reporter gene assay and enzyme-linked immunosorbent assay. Apoptosis was detected by flow cytometry, and the expression of proteins related to apoptosis pathway was detected by Western blot. Tests of peripheral blood mononuclear lymphocyte(PBMC)toxicity, platelet toxicity and mouse acute toxicity were done to make sure that it is not harmful to human. LFS-829 could bind covalently to the cysteine residue of the hydrophobic active pocket of CRM1. LFS-829 could selectively kill SNK6 and HANK-1 cells, with IC50 of 366 nmol/L and 158 nmol/L in 72 h, respectively, and cell morphology was significantly changed. LFS-829 at 800 nmol/L significantly inhibited the nuclear export function of CRM1, promoted nuclear assembly of IκB-α, down-regulated the transcriptional activity of NF-κB signaling pathway, significantly up-regulated the expression of apoptotic pathway protein p53, cleaved Caspase 3 and cleaved Caspase 9 and induced apoptosis, with no obvious killing effect on PBMC or platelets. It did not cause substantial tissue damage to mice at the high dose of 300 mg/kg, which shows its great prospect of future application.

Tibiocalcaneal arthrodesis via bone transport technique for traumatic talus infection or defect / 中华创伤杂志

Objective To investigate the clinical efficacy of tibiocalcaneal arthrodesis using bone transport technique in the treatment of traumatic talus infection or loss. Methods A retrospective case series study was conducted to analyze the clinical data of 15 patients with talus infection or loss admitted to the provincial hospital affiliated to Shandong University from June 2011 to October 2017. There were 13 males and two females, aged from 19 to 47 years, with an average age of 27 years. Thirteen patients had talus infection and two patients had talus loss. All patients underwent tibiocalcaneal fusion with external fixator using bone transport technique, including four patients treated with annular external fixator and 11 with unilateral external fixator. Six patients with severe infection underwent debridement at stage I and osteotomy at stage II, and the other nine underwent debridement and osteotomy at the same time. The length of new bone, the fixation time of external fixator and complications were recorded. The American Orthopedic Foot and Ankle Society ( AOFAS ) score was used to evaluate the efficacy. Results All patients were followed up for 18-35 months, with an average of 26 months. The length of new bone in proximal tibial osteotomy area was 5-16 cm, with an average of 9 cm. The external fixators were removed after bone healing at docking site and maturation of new bone. The fixation time of external fixator ranged from 13 to 27 months, with an average of 18 months. No complications such as needle breakage, recurrence of infection and calcaneal varus occurred, and the length of both lower limbs was equal. AOFAS score was increased from preoperative (42. 0 ± 3. 6)points (31-55 points) to (76. 0 ± 4. 2)points (69-86 points ) at the last follow-up. Conclusion Tibiocalcaneal arthrodesis using bone transport technique is proved to be effective in treating traumatic talus infection or loss, which can repair the bone defect after debridement, improve the ankle-hindfoot function and improve the quality of life.

Early usage of extraperitoneal pelvic packing plus temporary occlusion of abdominal aorta for treatment of pelvic fractures with hemodynamic instability / 中华创伤杂志

Objective To investigate the clinical outcomes of extraperitoneal pelvic packing combined with temporary occlusion of abdominal aorta in treatment of pelvic fractures with hemodynamic instability.Methods A retrospective case series study was made on 14 patients with pelvic fractures with hemodynamic instability managed by extraperitoneal pelvic packing plus temporary occlusion of abdominal aorta between December 2006 and December 2013.There were ten males and four females,with mean age of 38.2 years old (range,18-63 years).The fractures were classified according to the Tile classification,including two patients with type B1,two with type B2.2,one with type C1.1,two with type C1.2,two with type C1.3,three with type C2,and two with type C3.In addition,10 patients were with closed pelvic fractures and four with open pelvic fractures.All patients were diagnosed as hypovolemic shock once they were admitted.Every patient was given anti-shock treatment,temporary occlusion of abdominal aorta,and extraperitoneal pelvic packing instantly,in order to control hemorrhage of pelvic fracture after they were admitted.The operation time,red blood cell transfusion volume,preoperative and postoperative blood pressures,heart rates as well as other relevant parameters concerning death and survival were recorded and compared.Postoperative infection and wound healing status were recorded as well.Results The operation time was 50-70 minutes (mean,61 minutes).After surgery,the length of ICU stay was (10.9 ± 9.8) days and hospital stay was (23.1 ± 14.9) days.Red blood cell transfusion volume before and after surgery was (17.7 ± 2.2)U and (8.4± 1.7)U,respectively (P ＜ 0.05).The parameters of systolic pressures varied from preoperative (63.6 ± 2.1) mmHg to postoperative (90.9 ± 1.1) mmHg,and the parameters of heart rates declined from preoperative (106.2 ± 5.9) beats/min to postoperative (94.0 ± 6.2) beats/min,(P ＜ 0.05).Ten patients were available for follow-up of 8-24 months (mean,11.5 months).There were four deaths (29％) postoperatively,among which three were died from multisystem and organ failure,and one from severe brain injury.There were statistically significant differences between the survivors and the deaths in terms of time from injury to operation,average systolic pressures,and average heart rates (P ＜ 0.05).None had complications and wound was well healed.Conclusion For pelvic fractures with hemodynamic instability,extraperitoneal pelvic packing plus temporary occlusion of abdominal aorta has advantages of short manipulation time and effective outcomes,which can control the hemorrhage of pelvic fracture and ameliorate the hemodynamic status.

Treatment of open tibial plateau fractures with Hybrid external fixation / 中华创伤骨科杂志

Objective To evaluate the clinical results of minimally invasive surgery for open tibial plateau fractures using minimally open reduction and Hybrid external fixation.Methods From January 2011 through January 2015,9 complicated open tibial plateau fractures were treated with Hybrid external fixation.They were 6 males and 3 females,with an average age of 33.8 years (range,from 18 to 53 years).According to the Schatzker classification,there were 5 cases of type Ⅴ and 4 ones of type Ⅵ.According to the Gustilo classification,there were 5 cases of type Ⅱ,3 ones of type Ⅲ A and one of type Ⅲ B.All the patients were treated with Hybrid external fixation with or without minimally open reduction.Results The average operation time was 185.6 minutes (from 140 to 240 minutes).The average time for hospital stay was 18.4 days (from 10 to 45 days).The patients were followed up for an average of 15.6 months (from 6 to 36 months).All the 9 fractures got united after an average time of 4.3 months (from 3 to 7 months).The external fixation was removed after confirmation of fracture union.According to Merchant scores,the clinical results were evaluated as excellent in 4 cases,as good in 3,as fair in one and as poor in one.The knee joint was stable in each case.Pin tract infection was observed in one and wire loosening in one.Conclusion Hybrid external fixation with or without minimally open reduction is a safe and feasible surgical method which avoids massive soft tissue dissection for complicated open tibial plateau fractures.

Gauze packing for massive hemorrhage in pelvic fracture / 中华创伤杂志

Objective To investigate the clinical value of gauze packing for haemodynamically unstable pelvic fracture.Methods Between January 2006 and January 2014,gauze packing was used to treat haemodynamically unstable pelvic fracture in 42 patients consisting of 23 males and the 19 females aged 34.2 years (range,18 to 54 years).AO classification of the fracture was type B1 in 9,B2 in 5,B3 in 3,C1 in 13,C2 in 4,and C3 in 8 patients.All the patients were diagnosed with hypovolemic shock upon admission with the systolic pressure of (75.4 ± 4.3) mmHg and heart rate of (126.5 ± 12.4) beats/ min.Injury severity score (ISS) was (38.7 ± 6.2)points.Anti-shock treatment,internal or external fixation of pelvic ring,and gauze packing were performed immediately to control the hemorrhage following pelvic fracture.Results Systolic pressure was (95.2 ± 4.6) mmHg and mean heart rate was declined to (85.4 ± 13.2)beats/min after pelvis volume control and gauze packing,with significant differences compared to these preoperatively (P ＜ 0.05).Red blood cell transfusion before internal or external fixation and gauze packing was (15.0 ± 2.4) units versus (8.3 ± 1.5) units within the first postoperative 24 hours (P ＜ 0.05).Twenty-four out of the 42 patients underwent temporary abdominal aorta occlusion.Six patients died postoperatively with the death rate of 14％.Mean time of removing the packing gauze was (51.4 ± 10.3) hours (range,24-168 hours).Conclusion Anti-shock treatment with concurrent gauze packing and pelvis volume control is effective to arrest the massive hemorrhage in hemodynamically unstable pelvic fracture.

Management and outcome of pelvic fractures in elderly patients: a retrospective study of 40 cases / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Pelvic fractures are uncommon in elderly patients and so are infrequently addressed in the literature. The purpose of this study was to investigate the management and outcome of pelvic fractures in elderly patients.</p><p><b>METHODS</b>We retrospectively reviewed the records of pelvic fractures in elderly patients (age ≥55 years) who were treated in our department from September 1997 to May 2010.</p><p><b>RESULTS</b>A total of 40 elderly patients with pelvic fractures were identified. Their mean age was 65.8 years (range 55-87 years). About 68% (n = 27) were men. The average Injury Severity Score (ISS) was 17.8 (range 6-45). Twelve (30%) patients required blood transfusion (mean 10 units) during the first 24 hours. The fractures were most frequently due to falling from a standing position (48%). Almost half (48%) were grade I breaks. Associated injuries were present in 70% (n = 28) of patients, and 65% (n = 26) had medical co-morbidities. Altogether, 29 patients (73%) underwent non-surgical management of their pelvic fracture. The average hospital stay was 25 days. There were five in-hospital deaths and one death 10 months after discharge. High ISSs (>25) were associated with increased in-hospital mortality (P = 0.018). At the final assessment (mean follow-up 15 months), 52% of the surviving patients had experienced decreased self-sufficiency.</p><p><b>CONCLUSIONS</b>Pelvic fractures in elderly patients result in high morbidity and mortality rates. A high ISS (>25) can be used to identify a patient at high risk. We recommend aggressive resuscitation and intensive care for that patient. For patients with an unstable pelvic or displaced acetabular fracture (≥2 mm) who can endure surgery, open reduction and internal fixation can provide adequate fixation for early weight-bearing and restoration of the bone stock.</p>

Determination of 31 Triazine Herbicides in Farmland Soils by High Performance Liquid Chromatography-Tandem Mass Spectrometry / 分析化学

A high performance liquid chromatography-tandem mass spectrometric method ( HPLC-MS/MS ) was developed for the simultaneous determination of 31 kinds of triazine herbicides in farmland soils. Samples were extracted by accelerated solvent extraction ( ASE ) and purified by Oasis MCX solid phase extraction ( SPE) cartridges, and then analyzed by HPLC-MS/MS in multiple reaction monitoring ( MRM) mode with positive electrospray ionization. The analytical column was Phenomenex Luna C18 ( 150 mm í 2. 0 mm í3 μm) and the mobile phases were acetonitrile and water containing 0. 1% (V/V) formic acid. The limits of detection (S/N≥3) were 0. 008-0. 440 μg/L. All of the triazine herbicides had good linear responses with r≥0 . 996 and the average recoveries in the spiked levels of 0 . 40-40 . 0 μg/kg ranged from 76 . 9%-102 . 0%with the RSDs of 3 . 4%-10 . 3%. The HPLC-MS/MS method had been applied for the detection of the triazine herbicide residues in farmland soils from Shenyang region and the results showed that atrazine, simazine, prometryne and atrazine-desethyl were the main triazine herbicides in the region.

Comparison of the efficiency of the pelvic packing and the angioembolization for controlling pelvic fracture hemorrhoea / 中华骨科杂志

Objective To compare the efficiency of the pelvic packing and the angioembolization for controlling pelvic fracture hemorrhoea.Methods Data of 43 consecutive patients with pelvic fracture hemorrhoea who were enrolled in our hospital from April 2004 to April 2012 were retrospectively analyzed.There were 26 patients who had undergone pelvic packing,including 15 men and 11 women with an average age of 41.6 years (packing group).The causes of the fractures included road accident injury (12 cases),falling injury (8 cases) and the bruise injury caused by heavy object (6 cases).According to the Tile classification,there were 16 cases of type B and 10 cases of type C.There were 4 cases with open pelvic fractures and 5 associated with the abdomen trauma.There were 17 patients who had undergone angioembolization,including 10 men and 7 women,with an average age of 39.2 years (angio group).The causes included road accident injury (9 cases),falling injury (5 cases) and the bruise injury caused by heavy object (3 cases).There were 2 cases of type A,11 cases of type B and 4 cases of type C.The ISS,operation time,blood transfusion and the complication were all recorded respectively.Results For the packing group,the average ISS was 52.4± 15.3,and the operation time was 42.0±2.1 min.The blood transfusion was 15.0±4.7 U before the surgery and 6.0±1.6 U in the first 24 h after the surgery.The mean ICU stay was (8.0±3.6)d.And for the angio group,the average ISS was 40.6±12.4,and the operation time was 86.0±3.6 min.The blood transfusion before the surgery was 13.0±5.4 U vs.10.0±2.1 U in the first 24 h after the surgery,and the ICU stay was 11.0± 1.8 d.2 cases in the packing group underwent repacking and 6 cases in the angio group had received second angioembolization.Five cases died in the packing group but no one died of the hemorrhoea while 4 cases died in the angio group with one died of the hemorrhoea.There were 3 cases in the packing group suffering the deep infection while 1 suffered the superficial infection in the angio group.Conclusion The efficiency of the pelvic packing is higher than the angioembolization because of its shorter operation time and ICU stay,more effective blood control,less blood transfusion after surgery,and lower postoperative mortality.It is very suitable for the application at the local hospital and the national conditions nowadays.

Comparison of conventional X-ray fluoroscopy and ISO-C3D navigation for placement of sacroiliac screws in treatment of posterior pelvic ring fractures / 中华创伤杂志

Objective To compare the effect of ISO-C3D navigation and conventional C-arm fluoroscopy in iliosacral screws insertion for treatment of posterior pelvic ring injuries.Methods Sixty-five patients with posterior pelvic ring injuries managed by minimally invasive percutaneous iliosacral screws from June 2006 to January 2012 were reviewed.There were 37 males and 28 females,at age range of 18-63 years (mean 35.9 years).Pelvic fracture classification based on Tile system was type B1 in 10 cases,type B2 in 15,type B3 in nine,type C1 in 18 and type C2 in 13.Patients were divided into ISO-C3D navigation group (Group A,n =35) and C-arm fluoroscopy group (Group B,n =30) according to the difference in intraoperative fluoroscopy methods.Intraoperative fluoroscopy time,time cost in inserting a screw,patient satisfaction rate for bone reduction,bone union time and excellent-good rate of postoperative function were recorded.Results Eighty cannulated screws were inserted for the 65 patients.Average fluoroscopy time and time cost in inserting a screw were shorter in Group A than in Group B (P ＜0.01),but there was no statistical difference between the two gronps in patient satisfaction rate for bone reduction.No patient presented with infection,vascular nerve injury or other complications.Follow-up was 6-24 months (mean 12.7 months) for all the patients.Functional recovery showed no statistical difference between the two groups at postoperative 6 months.All fractures were healed and no delayed union or nonunion happened.Conclusion As compared with conventional C-arm fluoroscopy,computer-navigated surgery can reduce fluoroscopy time and improve screw insertion accuracy.

Internal fixation for fractures of the acetabular anterior column or pubic rami through minimally invasive ilioinguinal approach / 中华骨科杂志

ObjectiveTo explore the clinical effect of internal fixation for fractures of the acetabular anterior column or pubic rami through minimally invasive ilioinguinal approach.MethodsFrom June 2008 to June 2011,26 patients were surgically fixed with reconstructive plates through minimally invasive ilioinguinal approach.Sixteen cases were diagnosed as fractures of the acetabular anterior column,and ten as fractures of the pubic rami.The patient was positioned supine or lateral floating.The incision included two parts.The lateral part along the anterior one-third of the iliac crest about 3-5 cm.The insertion of the abdominal muscles and the origin of the iliacus were sharply incised from the crest.By subperiosteal dissection,the iliacus was elevated from the internal iliac fossa as far medially as to expose the anterior inferior iliac spine,iliopubic eminence and acetabular anterior column.The medial part of the incision was from the pubic tubercle transverse lateral extend 2-3 cm.Subperiosteal dissection to expose the superior pubic ramus.Two windows were dissected subperiosteal to connect through a tunnel along the anterior column of the acetabulum and pubic ramus.Fractures were reduced,and reconstruction plates were contoured and placed through the tunnel.Two or three screws were used at each window to fix the fractures.ResultsAccording to Matta evaluation system,anatomic reductions of the hip were in 13 cases,good in 11 and fair in 2 cases.Twenty-three patients were followed up from 6 to 30 months(mean,15.6 months).Hip functions were excellent in 13 patients,good in 6,and fair in 4 patients according to the D'Aubigne scores system.Pelvic functional results showed 12 were excellent,9 were good and 2 were fair according to Majeed scores system.No complications such as infection or deep venous thrombosis occurred.ConclusionThis modified ilioinguinal approach,with less operation time and low rate of complications,is simple and minimally invasive.It is easy for surgeons to perform plate moulding and could provide firm fixation.

Influence of different Chinese medical compounds on mouse exercise capacity and biochemical indexes / 中国组织工程研究

BACKGROUND:Many studies concerning influence of traditional Chinese medicine on animal movement capacity have been conducted.However,studies on the improvement of exercise capacity by traditional Chinese medicine are few,especially comparisons among traditional Chinese medicineOBJECTIVE:To explore the influence of different traditional Chinese medicine preparations on the exercise capacity in mice to screen compound preparations with precise effects.METHOD:A total of 80 8-week-old pure male Kunming mice were randomly assigned to 8 groups(n=10):control and compound 1-7 groups.There were no significant differences in body mass of all groups The compound 1 comprised Xuejie and Shexiang;compound 2 comprised Qingui,Baizhu and Baishao;compound 3 comprised Baizhu,Baizhi and Sanqi;compound 4 comprised Baizhi,Ruxiang,Danggui and Radix glycryrrhizae;compound 5 comprised Guiwei;compound 6 comprised Sichuan Honghua and Danshen;compound 7 comprised Danggui and Shexiang.Of the 7 prescriptions,compound 1-5 were empirical formula,compound 6 was common medicine used during training,and compound 7 was prescription of traditional Chinese medicine The 7 compound groupswere respectivelytreatedwith 1.17,0.78,0.78,1.17,7.02,5.53,and 11.70 g/kg per day for 4 weeks,and control group was intragastrically infused with normal saline.From day 4 to 6,load-free swimming training was performed 20 minutes a day for 3 days,followed by swimming for 6 days a week after 1 day of rest.The intensity was gradually increased frOm 30 minutes per day by 10 minutes per day for 2 hours,followed by loading swimming with load of 2%of the body mass,increased by 1%per day until the final experiment.During the entire procedure,a great intensity swimming training was performed every week to make the mice exhausted.Mice training and serum creatine kinase and lactate dehydrogenase 4 weeks following treatment were observed.RESULTS AND CONCLUSION:A total of 80 mice were included in the final analysis The compounds showed little influence on mice body mass;the compound 2 and compound 6 groups had longest exhaustive time All compounds inhibited serum creatine kinase activity following exercise,in particular compound 6 and 2(P＜0.05).Compared with control group,the serum lactate dehydrogenase activity of each compound group was decreased,in particular,compound 2 and 6 groups showed significant differences(P＜0.05).Compound 2 and 6 significantly enhanced the exercise capacity of mice and delayed injury of body.The mechanism may highly relate to components in the compounds,Danggui,Sichuan Honghua and Danshen.