Objective To investigate the effect of acupuncture combined with antidepressant on behavioral changes and 5-hydroxytryptamine 1A and 2A receptor ( 5-HT1AR and 5-HT2AR) mRNA expression in nucleus raphes dorsalis (NRD) of sleep deprivation depression (SDD) rats. Methods Eight normal Sprague Dawley (SD) rats were caged together without any stimulus or treatment, serving as the normal group. Thirty-two SD rats were given solitary raise for 21 days, together with chronic unpredictable mild stress ( CUMS) and rapid eye movement ( REM) sleep deprivation to establish the model. Twenty-eight rats completed the modeling successfully, and were divided into model group, acupuncture group, medicine group, and combination group, 7 rats in each group. Rats in the model group were given modeling treatment but without any intervention. Rats in the acupuncture group were given acupuncture on acupoint Yintang, Shenting and bilateral Taichong, acupuncture stimulation lasting 15 s every 10 min and acupuncture retention for 20 min in each day. Rats in the medicine group were given gastric gavage of Zoloft solution (0.83 mg·kg-1·d-1) and Alprazolam solution (0.067 mg· kg-1·d-1) , and rats in the combination group were given both acupuncture and medicine intervention. The intervention for the three intervention groups lasted for 7 days. Results Compared with the normal group, body weight, Open-field scores and sucrose preference of the model rats were significantly decreased on modeling day 7, 14, 21 (P<0.05). On modeling day 28, body weight and Open-field scores of each intervention group were significantly increased compared with those of the model group (P<0.05), and Open-field scores of combination group differed from those of acupuncture group and medicine group ( P<0.05). Only sucrose preference of combination group was improved significantly compared with the model group (P<0.05). Compared with the model group, NRD 5-HT1AR mRNA expression level was increased in the combination group (P<0.05), and NRD 5-HT2AR mRNA expression level was down-regulated in all of the three intervention groups ( P<0.05). Conclusion Acupuncture and antidepressant treatment covering 7 days can evoke rapid effect on SDD rats, which can improve the slow effect of antidepressant.

BACKGROUNDTransarterial chemoembolization (TACE) is the most widely used primary treatment for unresectable hepatocellular carcinoma (HCC) due to its survival benefit, though its clinical effect is still far from satisfactory. Jiedufang (JDF) granule preparation is a commonly used Chinese herbal medicine formula for HCC. The aim of this study was to evaluate the effect of combined therapy with TACE and JDF granule preparation in treatment of unresectable HCC on survival.

METHODSA retrospective study of TACE was performed in 165 patients with unresectable HCC who were admitted between January 2002 and December 2007 in Changhai Hospital, Shanghai, China. Of the 165 patients, 80 patients (study group) received combined therapy consisting of TACE and a long-term maintenance treatment with oral JDF granule preparation, and the remaining 85 patients (control group) received TACE alone. The survival rates of both groups were calculated by the Kaplan-Meier method. Factors possibly affecting survival were assessed by multivariate analysis in the Cox proportional hazard model, such as maximum tumor size, number of lesions, portal vein invasion, and etc.

RESULTSThe median overall survival was 9.2 months (95% CI: 6.94 - 11.46) in the study group versus 5.87 months (95% CI: 4.21 - 7.52) in the control group. In the study group,survival rates of the 1-, 2- and 3-year follow-up were 41.2%, 18.4%, and 9.6%, respectively. Significant independent prognostic factors identified by the Cox regression analysis were as follows: serum hepatitis B surface antigen (HBsAg) (P = 0.014), maximum tumor size (P = 0.027), number of lesions (P < 0.001), portal vein invasion (P < 0.001), and the therapy model (P = 0.006).

CONCLUSIONCombination therapy of TACE and JDF granule preparation may significantly prolong survival of patients with unresectable HCC.

Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Carcinoma, Hepatocellular ; drug therapy ; mortality ; pathology ; therapy ; Chemoembolization, Therapeutic ; methods ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Liver Neoplasms ; drug therapy ; mortality ; pathology ; therapy ; Male ; Middle Aged ; Retrospective Studies ; Survival Rate ; Treatment Outcome

Objective To design a novel double-leaf proximal humeral locking plate for fixing greater and lesser tuberosities in complex proximal humeral fractures,and evaluate its fixing stability by biomechanical tests.Methods Twelve fresh-frozen humerus specimens with intact rotator cuff were randomly divided into two groups (Group A and Group B) to establish the same greater and lesser tuberosities fracture models.Specimens in Group A were fixed with the double-leaf proximal humeral locking plate,while specimens in Group B were fixed with the proximal humeral internal locking system (PHILOS) and tension band suture,and a 3.5-mm cannulated screw was added to stabilize the lesser tuberosity.The tensile test on subscapularis,infraspinatus and teres,supraspi natus as well as the load-to-failure test on greater and lesser tuberosities were performed on specimens in two groups.Results For subscapularis tensile tests,displacements under 150 N tensile stretch and after fatigue test in Group A were both significantly smaller than those in Group B (P ＜ 0.05).For infraspinatus and teres tensile tests,there were no statistical differences between Group A and B in displacements under 150 N tensile stretch and after fatigue test (P ＞ 0.05).For supraspinatus tensile tests,there were no statistical differences between Group A and B in displacements under 90 N tensile stretch and after fatigue test (P ＞ 0.05).For load-to-failure tests on lesser tuberosity,the failure load in Group A was significantly greater than that in Group B (P ＜ 0.05),and the failure displacement in Group A was significantly smaller than that in Group B (P ＜ 0.05).For load-to-failure tests on greater tuberosity,there were no statistical differences between Group A and B in both the failure load and failure displacement (P ＞ 0.05).Conclusions Compared with the ordinary tension band suture plus cannulated screw for fixing lesser tuberosity,the novel double-leaf proximal humeral locking plate shows more obvious biomechanical stability,with the advantage of simultaneously fixing greater and lesser tuberosities.The research findings provide a new choice for the clinical treatment of complex proximal humeral fractures.

Objective To compare the stability of greater tuberosity fractures of humerus treated by three different fixation techniques (screws, tension band, locking plate, respectively) through biomechanical testing, so as to provide the biomechanics basis for choosing a better fixation in the clinical treatment for greater tuberosity fractures of humerus. Methods Standardized fracture models of the greater tuberosity from 18 fresh-frozen proximal humeri with intact rotator cuffs were created. The specimens were randomly assigned to 3 groups and treated by screws, tension band and locking plates, respectively. An increasing force was applied to the supraspinatus tendon. The force displacement curve and two parameters: LtYP(Load to 5 mm yield point) and Ltf(load to failure) were recorded. Results LtYP from the screw group, tension band group and locking plate group was (377±86), (499±90), (793±52) N, respectively, with significant differences among the three groups (P<0.01). Significant differences were also found between the groups as locking plate group (only 3 cases in locking plate group reached to 5 mm displacement before LtF in this study ) and screw group, locking plate group and tension band group, tension band group and screw group (P<0.01). LtF of screw group, tension band group and locking plate group was (744±112), (908±93), (979±143) N, respectively, showing significant differences among them, and which were also found between locking plate group and screw group, tension band group and screw group (P<0.01), but no significant differences were found between locking plate group and tension band group (P>0.05). Conclusions Locking plates show more obvious biomechanical stability than screws and tension band, which provides a new and better choice for treatment of isolated greater tuberosity fractures of humerus.

Objective To analyze the stress distribution and peak stress on midshaft clavicular fractures fixed by titanium elastic nail (TEN) or reconstruction plate, respectively. Methods CT data of the clavicle was adopted to reconstruct the intact clavicle model and the midshaft clavicular fracture models with the TEN and reconstruction plate fixation by using Mimics software. All the three dimensional finite element models were analyzed using Abaqus 6.9 software. The distal displacement, the peak stress and stress distribution on the distal clavicle under the axial load (250 N) and vertical load (250 N) were calculated for the three models. Results The axial displacement of the distal clavicle under the axial load showed TEN (0.23 mm)>intact clavicle (0.14 mm)>reconstruction plate (0.11 mm), respectively. While the vertical displacement of the distal clavicle under the vertical load was 5.12 mm for TEN, 3.71 mm for intact clavicle and 2.25 mm for reconstruction plate, respectively. But the peak stress of the clavicle under the axial load was 33.1 MPa for TEN, 18.7 MPa for reconstruction plate, and 15.5 MPa for intact clavicle model, respectively. And the peak stress under the vertical load was 146.3, 64.1, 56.1 MPa in the TEN, intact clavicle model, and reconstruction plate model, respectively. The stress distribution in TEN model under both kinds of loads was similar to that in intact clavicle model, while under the vertical load, the stress distribution in reconstruction plate model was clearly different with that in intact clavicle model. For the implants under the axial load, the peak stresses were 191.5, 52.3 MPa in the TEN model and reconstruction plate model, respectively, and the peak stress on implants under the vertical load was 1 248.0, 421.7 MPa in the TEN model and reconstruction plate model, respectively. Conclusions The TEN for treating midshaft clavicular fractures showed a stress distribution similar to the intact clavicle, with a higher peak stress and a higher peak implant stress at the fracture site. The reconstruction plate fixation for midshaft clavicular fractures was shown to be more stable, but with obvious stress shielding. Therefore, TEN is generally preferable for treating the simple displaced fractures of midshaft clavicle. However, the ipsilateral shoulder should avoid excessive exercise and weight bearing in the early postoperative period.

Objective To evaluate the biomechanical advantages of medial support screws (MSSs) in locking proximal humeral plate for treating proximal humerus fractures. Methods Thirty synthetic left humeri were randomly divided into 3 groups to establish the fracture models. Group A was fixed with a locking proximal humerus plate with medial cortical support, but without MSSs; group B was fixed with 3 MSSs, but without medial cortical support; group C was fixed with neither medial cortical support nor MSSs. Axial compression, torsion, shear stiffness and failure tests were applied on the specimens of the three groups. Results For axial compression tests, the maximum load of group A, B, C was (240.88±19.13), (169.04±19.26), (128.58±17.53) N, respectively; the axial stiffness of group A, B, C was (424.4±101.2), (230.7±40.54), (147.0±29.2) N/mm, respectively, showing significant differences (P<0.05). For torsion tests, the maximum torque of group C was (7.57±0.53) N•m, which was statistically different from both group A((8.92±0.25) N•m) and group B((9.09±0.31) N•m, P<0.05), and the torsional stiffness of group C((1.53±0.10) N•m/(°)) was statistically different from both group A((1.80±0.07) N•m/(°)) and group B((1.86±0.07) N•m/(°), P<0.05), but no significant differences were found between groups A and groups B in the maximum torque and torsional stiffness(P>0.05). For shear stiffness tests, the maximum load of group A, B, C was (444.71±20.87), (228.79±28.95), (188.73±26.15) N, respectively; the shear stiffness of group A, B, C was (70.0± 54.4), (183.89±29.64), (140.2±32.1) N/mm, respectively, showing significant differences (P<0.05). For failure tests, the failure load of group A ((2 949.76±355.08) N) was statistically different from both group B ((2 448.13±402.39)N) and group C ((2 222.55±336.41) N) (P<0.05), but no statistical differences were found between group B and group C (P>0.05). Conclusions Using three MSSs in locking plate for proximal humerus fractures shows optimal biomechanical properties, as compared to the situation without restoration of the medial column support. The reconstruction of the medial cortical support or MSSs for proximal humerus fractures helps to enhance the mechanical stability of the humeral head and prevent failure after internal fixation.

Objective To compare the biomechanical behavior of a triple Endobutton technique for anatomic reconstruction of coracoclavicular ligament and with a modified Weaver-Dunn procedure. Methods Twelve fresh frozen cadaveric shoulders were applied with 70 N in superior, anterior and posterior direction, respectively, to measure displacement of the acromioclavicular joint. The failure test with the load at the rate of 25 mm/min was conducted to record the failure load and failure mode. The specimens were then randomly assigned to 2 groups: the triple Endobutton technique group and the modified Weaver-Dunn procedure group for reconstruction and to conduct displacement test and failure test again. The stability and mechanical strength of acromioclavicular joints after reconstruction under different states were then compared. Results The triple Endobutton technique group had significantly less anterior ((8.72±1.41) mm vs (37.03±5.05) mm) and posterior ((8.03±3.68) mm vs (14.85±1.89) mm) displacement than that in the modified Weaver-Dunn procedure group after reconstruction (P<0.05), and the former had similar displacement ((7.81±2.22) mm anterior and (7.16±1.95) mm posterior) as compared to the intact state. There were no significant differences in superior displacement among the groups. The modified Weaver-Dunn procedure group had significantly smaller failure loads ((172±9) N) than that in the triple Endobutton technique group ((687±115) N) and the intact ligament group ((685±234) N) (P<0.05). Conclusions The triple Endobutton technique has less anterior and posterior displacement and its stability is more closely approximate to the intact ligament; meanwhile, it has similar strength as coracoclavicular ligaments, which can better restore the function of coracoclavicular ligaments.

Objective To design a novel double-leaf proximal humeral locking plate for fixing greater and lesser tuberosities in complex proximal humeral fractures, and evaluate its fixing stability by biomechanical tests. Methods Twelve fresh-frozen humerus specimens with intact rotator cuff were randomly divided into two groups (Group A and Group B) to establish the same greater and lesser tuberosities fracture models. Specimens in Group A were fixed with the double-leaf proximal humeral locking plate, while specimens in Group B were fixed with the proximal humeral internal locking system (PHILOS) and tension band suture, and a 3.5-mm cannulated screw was added to stabilize the lesser tuberosity. The tensile test on subscapularis, infraspinatus and teres, supraspinatus as well as the load-to-failure test on greater and lesser tuberosities were performed on specimens in two groups. Results For subscapularis tensile tests, displacements under 150 N tensile stretch and after fatigue test in Group A were both significantly smaller than those in Group B (P<0.05). For infraspinatus and teres tensile tests, there were no statistical differences between Group A and B in displacements under 150 N tensile stretch and after fatigue test (P>0.05). For supraspinatus tensile tests, there were no statistical differences between Group A and B in displacements under 90 N tensile stretch and after fatigue test (P>0.05). For load-to-failure tests on lesser tuberosity, the failure load in Group A was significantly greater than that in Group B (P<0.05), and the failure displacement in Group A was significantly smaller than that in Group B (P<0.05). For load-to-failure tests on greater tuberosity, there were no statistical differences between Group A and B in both the failure load and failure displacement (P>0.05). Conclusions Compared with the ordinary tension band suture plus cannulated screw for fixing lesser tuberosity, the novel double-leaf proximal humeral locking plate shows more obvious biomechanical stability, with the advantage of simultaneously fixing greater and lesser tuberosities. The research findings provide a new choice for the clinical treatment of complex proximal humeral fractures.

Background: Technical aspects of the correct placement of medial support locking screws in the locking plate for proximal humerus fractures remain incompletely understood. This study was to evaluate the clinical relationship between the number of medial support screws and the maintenance of fracture reduction after locked plating of proximal humerus fractures. Methods: We retrospectively evaluated 181 patients who had been surgically treated for proximal humeral fractures (PHFs) with a locking plate between September 2007 and June 2013. All cases were then subdivided into one of four groups as follows: 75 patients in the medial cortical support (MCS) group, 26 patients in the medial multiscrew support (MMSS) group, 29 patients in the medial single screw support (MSSS) group, and 51 patients in the no medial support (NMS) group. Clinical and radiographic evaluations included the Constant-Murley score (CM), visual analogue scale (VAS), complications, and revision surgeries. The neck-shaft angle (NSA) was measured in a true anteroposterior radiograph immediately postoperation and at final follow-up. One-way analysis of variance or Kruskal-Wallis test was used for statistical analysis of measurement data, and Chi-square test or Fisher's exact test was used for categorical data. Results: The mean postoperative NSAs were 133.46° ± 6.01°, 132.39° ± 7.77°, 135.17° ± 10.15°, and 132.41° ± 7.16° in the MCS, MMSS, MSSS, and NMS groups, respectively, and no significant differences were found (F = 1.02, P = 0.387). In the final follow-up, the NSAs were 132.79° ± 6.02°, 130.19° ± 9.25°, 131.28° ± 12.85°, and 127.35° ± 8.50° in the MCS, MMSS, MSSS, and NMS groups, respectively (F = 4.40, P = 0.008). There were marked differences in the NSA at the final follow-up between the MCS and NMS groups (P = 0.004). The median (interquartile range [IQR]) NSA losses were 0.0° (0.0-1.0)°, 1.3° (0.0-3.1)°, 1.5° (1.0-5.2)°, and 4.0° (1.2-7.1)° in the MCS, MMSS, MSSS, and NMS groups, respectively (H = 60.66, P < 0.001). There were marked differences in NSA loss between the MCS and the other three groups (MCS vs. MMSS, Z = 3.16, P = 0.002; MCS vs. MSSS, Z = 4.78, P < 0.001; and MCS vs. NMS, Z = 7.34, P < 0.001). There was also significantly less NSA loss observed in the MMSS group compared to the NMS group (Z = -3.16, P = 0.002). However, there were no significant differences between the MMSS and MSSS groups (Z = -1.65, P = 0.225) or the MSSS and NMS groups (Z = -1.21, P = 0.099). The average CM scores were 81.35 ± 9.79, 78.04 ± 8.97, 72.76 ± 10.98, and 67.33 ± 12.31 points in the MCS, MMSS, MSSS, and NMS groups, respectively (F = 18.68, P < 0.001). The rates of excellent and good CM scores were 86.67%, 80.77%, 65.52%, and 43.14% in the MCS, MMSS, MSSS, and NMS groups, respectively (χ = 29.25, P < 0.001). The median (IQR) VAS scores were 1 (0-2), 1 (0-2), 2 (1-3), and 3 (1-5) points in the MCS, MMSS, MSSS, and NMS groups, respectively (H = 27.80, P < 0.001). Functional recovery was markedly better and VAS values were lower in the MCS and MMSS groups (for CM scores: MCS vs. MSSS, P < 0.001; MCS vs. NMS, P < 0.001; MMSS vs. MSSS, P = 0.031; and MMSS vs. NMS, P < 0.001 and for VAS values: MCS vs. MSSS, Z = 3.31, P = 0.001; MCS vs. NMS, Z = 4.64, P < 0.001; MMSS vs. MSSS, Z = -2.09, P = 0.037; and MMSS vs. NMS, Z = -3.16, P = 0.003). Conclusions Medial support screws might help enhance mechanical stability and maintain fracture reduction when used to treat PHFs with medial metaphyseal comminution or malreduction.
Aged ; Bone Plates ; Bone Screws ; Female ; Fracture Fixation, Internal ; methods ; Humans ; Humerus ; Male ; Middle Aged ; Retrospective Studies ; Shoulder Fractures ; surgery ; Treatment Outcome

OBJECTIVETumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resistance greatly limits the clinical therapeutic efficacy of TRAIL. Elucidating the molecular mechanism underlying TRAIL resistance will be fundamental to resolving this problem.

METHODSNuclear and cytoplasmic protein extraction and immuno？uorescence (IF) assay were used to detect changes in heterogeneous nuclear ribonucleoprotein K (hnRNPK) localization in H1299 cells. The evaluation of cell apoptosis in cells transfected with GFP-hnRNPK, GFP-hnRNPK S284/353A, or GFP-hnRNPK S284/353D mutant was performed using cleaved caspase-3 antibody. The gene expression of XIAP was tested by quantitative RT-PCR.

RESULTSPreviously, we reported that hnRNPK antagonized TRAIL-induced apoptosis through inhibition of PKC-mediated GSK3β phosphorylation. In this study, we further demonstrate that TRAIL treatment induces cytoplasmic accumulation of hnRNPK in H1299 cells. The hnRNPK localized in the cytoplasm has a higher capacity to antagonize TRAIL-induced apoptosis. Both ERK1/2 signaling inhibitor U0126 and ERK-phosphoacceptor-site mutant (GFP-hnRNPK S284/353A) diminish cytoplasmic accumulation of hnRNPK induced by TRAIL. Moreover, we show that XIAP is involved in hnRNPK-mediated TRAIL resistance in H1299 cells.

CONCLUSIONTaken together, these results give new insights into the understanding of the molecular mechanism associated with TRAIL resistance in lung adenocarcinoma.

Apoptosis ; physiology ; Cell Line, Tumor ; Gene Expression Regulation ; physiology ; Heterogeneous-Nuclear Ribonucleoprotein K ; genetics ; metabolism ; Humans ; Mitogen-Activated Protein Kinase 1 ; genetics ; metabolism ; Mitogen-Activated Protein Kinase 3 ; genetics ; metabolism ; TNF-Related Apoptosis-Inducing Ligand ; genetics ; metabolism ; Up-Regulation ; physiology ; X-Linked Inhibitor of Apoptosis Protein ; genetics ; metabolism