Chronic activation of the B-cell antigen receptor (BCR) signaling pathway performs a critical function in the pathogenesis of numerous subtypes of B-cell malignancies and transforms normal cells into malignant cells. Bruton tyrosine kinase (BTK) is a member of the TEC family of tyrosine kinases and is a key regulator of the BCR signaling pathway. BTK inhibition has emerged as a new target for therapeutic intervention in B-cell malignancies. This review summarizes recent developments of BTK inhibitors in B-cell malignan-cies.

Objective To observe the short-term effect of radial head replacement for the treatment of terrible triad of the elbow.Methods In the period between June 2011 and June 2012,the radial head replacements were carried out in six patients with terrible triad of elbow.There were five acute elbow fracture-dislocation cases and one old fractnre case.All cases underwent open reduction and fixation coronoid fracture with screws or nonabsorbable sutures,radial head replacement,repair of lateral ligament complex and repair or reconstruction of annular ligament.All patients initiated the rehabilitation program under supervision within 5-7 days after surgery.The X-ray and Computed tomography of elbow was used to evaluate the posi tion of radial head prosthesis.Functional outcome of elbow was assessed by Mayo Elbow Performance Score (MEPS) and complications.Results All patients were participated in follow-up for 10-24 months and the mean duration of follow-up was 16.8 months.The MEPS was from 85 to 95 points and the mean MEPS was 91.7 points.The outcome of MEPS was excellent in 5 cases,good in 1 case.The range motion of elbow flexion was from 82 to 95 degrees and the average of elbow flexion was 87 degrees; the range motion of extension was from 15 to 32 degrees and the average of elbow extension was 21 degrees.The range motion of fore-ann pronation was from 82 to 90 degrees with 86 degrees in average.The motion range of supination was from 45 to 80 degrees with 56 degrees in average.All cases got persistent stability in elbow with painless movement.None of patient suffered traumatic arthritis and infection.The motion range of elbow was restricted due to the unfit relative position of radial head prosthesis and capi tellum in one case,characterized by decreasing radiocapitellar joint space.Two cases developed into heterotopic ossification in elbow without hampering the motion range of elbow.Conclusion The outcome of the radial head replacement on the treatment of radial head fracture in the elbow terrible triad was satisfactory.However,the longer duration of observation was essential to verify the favorable effect of radial head replacement on dealing with terrible triad in elbow.

BACKGROUND:Ischemia/reperfusion injury can cause the necrosis of cardiomyocyte,and it can also induce cell apoptosis.However,cell apoptosis may be the main death type of cardiomyocyte at the early stage of infarction,and it may be one of causes for expanding myocardial infarction area.OBJECTIVE:The goal of this study was to observe the anti-apoptotic effect of adenosine (ADO) preconditioning on cardiomyocytes during the ischemia/reperfusion,and to investigate the role of apoptosis-related gene protein Bcl-2 and Bax.DESIGN:A randomized controlled animal experiment.SETTING:First College of Clinical Medical Science,China Three Gorges University&Department of Cardiology,Yichang Central People's Hospital.MATERIALS:Thirty-six healthy male rabbits of clean grade,weighing 2.5 to 3.0 kg,were provided by Laboratory Animal Department,Tongji Medical College,Huazhong University of Science and Technology.The protocol was carried out in accordance with animal ethics guidelines for the use and care of animals.All rabbits were divided into 3 groups according to random number table.There were 12 animals in either control,ADO or ADO+DPCPX (an adenosine A1 receptor antagonist).METHODS:This experiment was carried out in the Central Laboratory,China Three Gorges University between October 2005 and October 2006.Ex vivo rabbit myocardial ischemia/reperfusion models were prepared.After being anesthetized,the rabbits were performed anticoagulation with heparin and carried out Langendorff retroperfusion.In the control group,the hearts of animals subjected to 40 minutes of ischemia and 60 minutes of reperfusion.Six of them were used for determining myocardial infarct size after reperfusion,another six for cardiomyocyte apoptosis,gene expression and ultrastructural analysis of myocardium.In the ADO group:The ADO hearts were continuously infused with 10 μmol/L of adenosine 30 minutes before ischemia,and operated according to the requirement of control group.In the DPCPX roup:the isolated hearts of animals were infused for 15 minutes with 10 mmol/L of DPCPX 45 minutes before ischemia.and operated in accordance with ADO group.MAIN OUTCOME MEASURES:①The heart rate and blood pressure of animals in 3 groups were measured during ischemia/reperfusion process.②The infarct size was determined by triphenyltetrazolium chloride(TTC) staining.③The apoptotic index of cardiomyocytes was detected by histological TUNEL staining and DNA ladder on agarose gel electrophoresis.④Apoptosis-related protein Bcl-2 and Bax expressions were detected by in situ immunohistochemical staining.RESULTS:Thirty-six rabbits were enrolled in the final analysis.①Comparison of heart rate and blood pressure:During the process of ischemia/reperfusion,both heart rate and blood pressure were persistently decreased significantly (P＜0.01).There were no significant differences in two indexes between any two groups (P＞0.05).②Comparison of myocardial infarct size:There were no significant differences in myocardial infarct size among the control group,ADO group and DPCPX group (P＞0.05).The myocardial infarct size of rabbits in the ADO group was significantly smaller than that in the control group.It suggested that ADO preconditioning could contract the myocardial infarct size of rabbits.The myocardial infarct size of rabbits in the ADO+DPCPX group was significantly larger than that in the ADO group,but significantly smaller than that in the control group (P＜0.01).It suggested that DPCPX could partially inhibit the protective effect of ADO.③Comparison of apoptosis of cardiomyocytes: Apoptotic cells were not found in the non-ischemic myocardial tissue,but found in the infarct tissue and infarct edge ischemic tissue.Apoptotic cells in the control group and ADO+DPCPX group were significantly more than those in the ADO group.Apoptotic index in the control group and ADO+DPCPX group was significantly higher than that in the control group,respectively (P＜0.01).④Comparison of apoptosis-related protein expression:The absorbance of Bax in the ADO group was significantly lower than that in the control group(P＜0.01).The absorbance of Bax in the ADO+DPCPX group was significantly lower than that in the control group,but significantly higher than that in the ADO group (P＜0.01).The value of Bcl-2/Bax in the control group was significantly lower than that in the ADO group (P＜0.01).The value of Bcl-2/Bax in the ADO+DPCPX group was significantly higher than that in the control group,but significantly higher than that in the ADO group(P＜0.01).CONCLUSION:Exogenous ADO inhiblts reperfusion-induced apoptosis of cardiomyocytes,which is partially mediated by DPCPX:Down-regulation of apoptosis-related Bax protein plays an important role in the anti-apoptotic effect of exogenous ADO.

This study was designed to assess the effect of a home-bred poly-DL-lactide (PDLLA) rods on experimental fracture healing. An operation was performed to create bilateral ulnar and radial fractures of forearm in 15 rabbits. The right sides were fixed with 2 PDLLA (Mv = 34 x 10(4), 1.6 mm x 1.6 mm x 30 mm) rods, and the contralateral sides were fixed with 2 Kirschner wires to be used as controls. After operation, casts were used for external fixation, and the joint above and the joint below the fracture were immobilized. The casts were removed at the 6th week after operation. The specimens were removed at specific intervals between 2 and 12 weeks. Histologically, the light microscopy and scanning electron microscopy evaluation of the rabbit ulnar and radial fractures fixation revealed that, the fractured bone gradually healed and the PDLLA rods properly fixed on the fracture area during the implanted period. However, results suggest that internal fixation by absorbable material made the course of fracture healing slower than that in the control group, but the osteogenesis appeared to be normal. In the absorbable group, the collagenous fiber was characterized by order and orientation, and calcified normally. In conclusion, this kind of PDLLA rods have an effect on delaying the process of the normal union of fracture and should be applicable to fractures where the tissues are rich in blood supply.
Absorbable Implants ; Animals ; Female ; Fracture Fixation, Intramedullary ; instrumentation ; Fracture Healing ; Internal Fixators ; Male ; Polyesters ; Rabbits ; Radius Fractures ; surgery ; Ulna Fractures ; surgery

Objective To investigate the effects of acupuncture rehabilitation techniques combined with Xingnaojing injection on functional recovery and the plasam level of glial fibrillary acidic protein (GFAP) in patients with severe traumatic brain injury (STBI).Methods Eighty-four patients with STBI admitted to Department of Neurosurgery in Jiuquan People's Hospital from October 2013 to December 2015 were enrolled,they were divided into observation group (44 cases) and control group (40 cases) by random number table,all patients received the routine basic treatment,such as decreasing intracranial pressure,anti-infection,neural nutrition therapy,etc.In addition,the observation group was treated with acupuncture rehabilitation training (each training 50 minutes,1-2 times a day,10 times as a course of treatment,a total of 5 courses) and Xingnaojing injection (in 0.9％ normal saline or 5％ glucose injection 250 mL intravenous infusion,one time a day,10 days as a course of treatment,a total of 3 courses).The evaluation score of Montreal cognitive assessment (MoCA),Modified Barthel index (MBI),Fugl-Meyer assessment (FMA) of motor function score and the plasma levels of GFAP and myelin basic protein (MBP) were measured before and after treatment in the two groups.Results After treatment,the MoCA,MBI and FMA scores were significantly higher in two groups than those before treatment (all P ＜ 0.05),the contents of MBP and GFAP were significantly lower than those before treatment,and the changes in observation group were more significant than those in control group [visual space and execution capability (score):4.99 ± 0.67 vs.3.42 ± 0.73,denomination capability (score):2.98 ± 0.77 vs.2.84 ± 0.47,delayed memory (score):5.76± 0.33 vs.3.87± 2.08,attention (score):6.17± 0.65 vs.4.75 ± 0.81,speech capability (score):3.51 ± 0.46 vs.2.04 ± 0.13,abstract thinking capability (score):2.94 ± 0.27 vs.1.58 ± 0.96,orientation force (score):6.02±0.65 vs.4.88±0.62,FMA score:68.71 ±34.17 vs.41.13 ± 14.82,MBI score:69.12± 10.45vs.37.63±6.11,MBP (μg/L):1.32±0.23 vs.5.31±0.79,GFAP (μg/L):0.19±0.08 vs.0.39±0.04,all P ＜0.05].Conclusions Acupuncture rehabilitation training combined with Xingnaojing injection may obviously improve the cognitive and motor functions in patients suffered from STBI,and clinically the combined treatment is worthwhile to be used extensively.

Objective To explore the distribution rule of metastatic lymph node in nasopharyngeal carcinoma (NPC) by magnetic resonance imaging (MRI).Methods 315 histopathologically proved NPC patients were studied retrospectively.All patients had had their nasopharynx scanned by MRI with plain and contrast enhanced sequences.The distribution of lymph node was divided into six cervical levels plus retro- pharyngeal nodes(RN) according to RTOG guidelines proposed in 2003.Results 254 out of 315 patients (80.6%) had lymph node involvement,with 81 in the right neck alone,72 left neck alone,and 101 both necks;73 in RN alone,21 neck node alone,and 160 both necks and RN node.Skip metastasis was found in only 4 patients (1.6%).There was significant difference in BN metastasis between the primary tumor be- ing located merely on the superior/posterior wall and lateral wall (78% vs 49%,P＜0.01).The incidence of lymph node metastasis in T1,T2,T3 and T4 patients was 73.5%,91.2%,71.9%,73.5% (P＞0.05), respectively,without significant difference between early or advanced T stage in node distribution (P＞0.05).Conclusions The incidence of lymph node metastasis is high in nasopharyngeal carcinoma,with retropharyngeal node being the most commonly involved,but the incidence of skip metastasis is very low. There is no significant difference between T stage and the incidence of lymph node metastasis.So is the dis- tribution of metastatic node.

Percutaneous coronary intervention(PCI) has become one of the most important therapeutic methods for atherosclerotic heart disease(AHD),but the following complications such as stent thrombosis and restenosis af- fected its long-term efficacy.Platelet activation was a key component of thrombosis of during perioperative period PCI.As one of the most effective antiplatelet drugs,clo- pidogrel has been established its important role in preven- ting thrombosis during perioperative period of PCI.After several large-scale clinical trials in recent years.

ObjectiveTo investigate the prognostic value of fluid responsiveness in patients with acute respiratory stress syndrome (ARDS).Methods Fifty-nine mechanically ventilated patients with ARDS were enrolled.Their stroke volume variations (SVV) were detected by pulse contour continuous cardiac output (PiCCO) analysis device,and then the patients were subsequently divided into fluid responsive group (SVV≥15％) and fluid non-responsive group (SVV ＜ 15％ ).The differences in 28-day survival,length of ICU stay and duration of mechanical ventilation between the 2 groups were compared.Thereafter,the 28-day survival of patients was analyzed by Kaplain-Meier survival model and the relationship between SVV and mortality within 28 days was analyzed by logistic regression model.Results In comparison with fluid non-responsive group,the 28-day survival of fluid responsive group was significantly increased (85.3％ vs.56.0％,P =0.012),the length of ICU stay was significantly shortened [( 13.1 ±5.2 ) d vs. (21.6±9.0) d,P=0.008],and the duration of mechanical ventilation was significantly shortened as well [( 11.4 ± 5.3 ) d vs.( 18.3 ± 4.9) d,P =0.022] ; Logistic analysis revealed that SVV ＜ 15％ increased the risk of 28-day mortality ( OR =4.82 ; 95％ CI:2.67 ～ 11.71,P =0.009 ).ConclusionsSVV-based fluid responsiveness can be served as a prognostic predictor for ventilated patients with ARDS.

OBJECTIVETo found the subcellular location of the human gene 6 transactivated by nonstructural protein 5A of hepatitis C virus (NS5ATP6).

METHODSGreen fluorescent protein (GFP) expression vector pEGFP- NS5ATP6 was established. The pEGFP- NS5ATP6 was transfected into HepG2 cells, and analyze the subcellular location of the proteins expressed by NS5ATP6 through Green fluorescent microscopy after 24 hours.

RESULTSThe pEGFP- NS5ATP6 gene was successful cloned, NS5ATP6 can express protein in cells and subcellularly located in cell plasma.

CONCLUSIONNS5ATP6 can express protein, and the protein expressed by NS5ATP6 subcellularly located in cell plasma.

Cell Line, Tumor ; Genetic Vectors ; genetics ; metabolism ; Hepacivirus ; Humans ; Intracellular Space ; metabolism ; Microscopy, Fluorescence ; Transcriptional Activation ; Transfection ; Viral Nonstructural Proteins ; metabolism

Objective To detect specific polymorphisms in Toll-interleukin 1 receptor domain containing adaptor protein(TIRAP) coding region for Chinese Han population, and verify whether they are associated with susceptibility to tuberculosis. Methods Search TIRAP polymorphisms by sequencing in small sample; detect single nucleotide polymorphism(SNP) by ligase detection reaction technique in large sample; analyze whether polymorphisms are related to tuberculosis by statistic methods. Results Four polymorphisms were present in the TIRAP coding region. 394A had higher frequencies in the tuberculosis(TB)group than the control. But allelic and genotypic analysis showed that there were no significant difference in statistic between TB patients and controls(P>0.05). The SNP G164A mutation related with TB patient's condition. Comparing to controls, retreatment patients' allelic frequencies had significant difference in statistic(P<0.05), sputum positive patients and lung cavitation patients had lower 164A frequencies. Conclusion TIRAP coding region polymorphisms may be risk factors for TB occurrence and development in Chinese Han population.