A dopamine receptor D2 genetic polymorphism associated with transition to mental disorders in a cohort of individuals with at-risk mental state for psychosis

Objectives: To test the association of 45 single nucleotide polymorphisms (SNPs) with transition to psychiatric disorders in a cohort of individuals at ultrahigh risk (UHR) mental state for psychosis. Methods: Through general population screening, 88 non-help-seeking UHR subjects and 130 healthy control individuals were genotyped for 45 SNPs related to psychosis. They were followed for a mean of 2.5 years, and conversion to psychotic and to general psychiatric disorders was assessed. Genotype frequencies between controls, converters, and non-converters were analyzed. Results: There were no differences in sociodemographics between controls and UHR. Also, UHR converters and non-converters had no differences in their baseline symptoms scores. The dopamine receptor D2 gene (DRD2) SNP rs6277 was significantly more common among UHR who transitioned to psychosis (p < 0.001) and to UHR who transitioned to any psychiatric disorders (p = 0.001) when compared to UHR who did not transition. The rs6277 T allele was related to psychiatric morbidity in a dose-response fashion, being significantly more frequent in UHR converters than UHR non-converters and control subjects (p = 0.003). Conclusion: Our findings suggest that rs6277 could potentially constitute a genetic marker of transition to psychiatric disorders in subjects with at-risk mental states, warranting further investigation in larger samples.

Colgajo giratorio retroauricular / Retroauricular flip-flop flap

Resumen El colgajo retroauricular en isla (flip-flop flap) fue descrito por Masson en 1972 y consiste en tejido dermoepidérmico irrigado por un pedículo de patrón aleatorio subcutáneo de ramas de la arteria auricular posterior. Proviene de la región mastoidea y retroauricular y aporta buena cobertura para la región anteromedial del pabellón auricular. Se describen dos casos, en que se realizó cobertura inmediata secundario a un defecto de la concha auricular posterior a resección neoplásica, obteniendo resultados satisfactorios y sin complicaciones.

Abstract The retroauricular island flap (flip-flop flap), was described by Masson in 1972 and consists on dermoepidermal tissue irrigated by a random subcutaneous pedicle of branches of the posterior auricular artery. It comes from the mastoid and retroauricular region and provides a good coverage for the anteromedial region of the pinna. Two cases are described, in which immediate coverage was performed secondary to a defect in the auricular concha after a neoplastic resection, obtaining satisfactory results without complications.

A new perspective of triptolide-associated hepatotoxicity: the relevance of NF- B and NF- B-mediated cellular FLICE-inhibitory protein

Previously, we proposed a new perspective of triptolide (TP)-associated hepatotoxicity: liver hypersensitivity upon lipopolysaccharide (LPS) stimulation. However, the mechanisms for TP/LPS-induced hepatotoxicity remained elusive. The present study aimed to clarify the role of LPS in TP/LPS-induced hepatotoxicity and the mechanism by which TP induces liver hypersensitivity upon LPS stimulation. TNF- inhibitor, etanercept, was injected intraperitoneally into mice to investigate whether induction of TNF- by LPS participated in the liver injury induced by TP/LPS co-treatment. Mice and hepatocytes pretreated with TP were stimulated with recombinant TNF- to assess the function of TNF- in TP/LPS co-treatment. Additionally, time-dependent NF-B activation and NF-B-mediated pro-survival signals were measured and . Finally, overexpression of cellular FLICE-inhibitory protein (FLIP), the most potent NF-B-mediated pro-survival protein, was measured and to assess its function in TP/LPS-induced hepatotoxicity. Etanercept counteracted the toxic reactions induced by TP/LPS. TP-treatment sensitized mice and hepatocytes to TNF-, revealing the role of TNF- in TP/LPS-induced hepatotoxicity. Mechanistic studies revealed that TP inhibited NF-B dependent pro-survival signals, especially FLIP, induced by LPS/TNF-. Moreover, overexpression of FLIP alleviated TP/LPS-induced hepatotoxicity and TP/TNF--induced apoptosis . Mice and hepatocytes treated with TP were sensitive to TNF-, which was released from LPS-stimulated immune cells. These and other results show that the TP-induced inhibition of NF-B-dependent transcriptional activity and FLIP production are responsible for liver hypersensitivity.

KLF5 suppresses TRAIL-induced cell apoptosis in PC-3 prostate cancer cells / 西安交通大学学报(医学版)

Objective: To explore the possibility of promoting tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-induced apoptosis in prostate cancer PC-3 cell by inhibiting Krüppel-like factor 5 (KLF5). Methods: MTT assay, flow cytometry, Western blot assay and qRT-PCR assay were deployed to detect the cell viability, apoptosis and apoptotic markers in KLF5-inhibited and TRAIL-induced PC-3 cells. Results: After KLF5 was inhibited in TRAIL-induced PC-3 cells, cell viability reduced, apoptosis enhanced, the expressions of DR4 and DR5 increased while the expression of cellular fas-associated death domain-like interleukin-1β converting enzyme inhibitory protein (c-FLIP) decreased. Conclusion: Inhibiting KLF5 suppresses cell viability by promoting TRAIL-induced apoptosis in prostate cancer cell PC-3. It may be a potential means to treat hormone-insensitive prostate cancer.

Simplifying the ShangRing technique for circumcision in boys and men: use of the no-flip technique with randomization to removal at 7 days versus spontaneous detachment / 亚洲男科学杂志(英文版)

To assess safety of the no-flip ShangRing male circumcision technique and to determine clinical course and safety of spontaneous detachment (i.e., allowing the device to fall off), we conducted a case series of no-flip ShangRing circumcision combined with a randomized controlled trial of removal 7 days postcircumcision versus spontaneous detachment at two health facilities in Kenya. The primary outcome was the safety of the no-flip technique based on moderate and severe adverse events (AEs) during the procedure and through 42-day follow-up. A main secondary outcome was clinical course and safety of spontaneous detachment. Two hundred and thirty males 10 years and older underwent no-flip circumcision; 114 randomized to 7-day removal and 116 to spontaneous detachment. All circumcisions were successfully completed. Overall 5.3% (6/114) of participants in the 7-day group and 1.7% (2/116) in the spontaneous group had an AE; with no differences when compared to the 3% AE rate in historical data from African studies using the original flip technique (P = 0.07 and P = 0.79, respectively). Overall 72.4% (84/116) of participants in the spontaneous group wore the ShangRing until it detached. Among the remaining (27.6%; 32/116), the ring was removed, primarily at the participants' request, due to pain or discomfort. There was no difference in AE rates (P = 0.169), visit day declared healed (P = 0.324), or satisfaction (P = 0.371) between randomization groups. The median time to detachment was 14.0 (IQR: 7-21, range: 5-35) days. The no-flip technique and spontaneous detachment are safe, effective, and acceptable to boys and men 10 years and older. Phimosis and penile adhesions do not limit successful ShangRing circumcision with the no-flip technique.

Application of three-dimensional SPACE magnetic resonance imaging in accurate measurement of implant volume in breast surgery / 中华整形外科杂志

Objective@#The study is to assess the accuracy and reliability of three-dimensional simulated magnetic resonance imaging with silicone-excitation SPACE (sampling perfection with application optimized contrast using different flip angle evolutions) sequence for estimating implant volume.@*Methods@#(1) MRI examinations of 10 silicone implants (Wuhan Tongji Hospital from October 2018 to December 2018) were performed with T2, H2O-excitation SPACE sequence (T2-spc-H2O) and silicone-excitation SPACE sequence (T2-spc-Silicone) to find the most accurate method to estimate implant volume by ITK-SNAP. The effect of implant deformation and slice thickness of T2-spc-Silicone on volume measurement were investigated. (2) 13 normal patients and 6 patients with implant complications (Wuhan Tongji Hospital from March 2017 to May 2019) were enrolled for testing the accuracy and reliability of T2-spc-Silicone for volume measurement in vivo. The data were analyzed using Prism 8.0 software. The paired student t-test was used to compare the difference of two groups. One-way ANOVA was used to compare the difference of multiple groups. P<0.05 was considered statistically significant.@*Results@#The absolute volume differences of T2, T2-spc-H2O, T2-spc-Silicone were (42.19±2.31) ml, (23.27±1.55) ml and (6.28±1.22) ml. The absolute volume differences of T2-spc-Silicone group was significantly less than T2-spc-H2O and T2 group in vitro(F=195.3, P<0.001). No significant difference(F=1.36, P=0.22)was shown between the normality group and the deformation group for estimating the volume of implants with the slice thickness of SPACE increased from 0.5 mm×0.5 mm×0.5 mm to 5.0 mm×5.0 mm×5.0 mm. Besides, the slices thickness of SPACE from 0.5 mm×0.5 mm×0.5 mm to 5.0 mm×5.0 mm×5.0 mm did not significantly affect the accuracy of volume measurement of the implants in deformation state(F=1.22, P=0.29). The measurement error of SPACE was (8.82±0.99) ml in normal patients. Moreover, there was no significant difference between measured volume[(226.4±12.76)ml] and actual volume of implants[(225.9±11.94) ml](t=0.31, P=0.76)in patients with implant complications. The result showed excellent intraobserver reliability (ICC=0.997) and internal consistency ranged from 0.986 to 0.997 (P<0.001).@*Conclusions@#The method to measure implant volume by silicone-excitation SPACE sequence had desirable accuracy and reliability. The deformation of the implant and the slice thickness of the SPACE sequence did not exhibit a significant effect on the accuracy of volume measurement.

Simplifying the ShangRing technique for circumcision in boys and men: Use of the no-flip technique with randomization to removal at 7 days versus spontaneous detachment / 亚洲男科学杂志(英文版)

To assess safety of the no-flip ShangRing male circumcision technique and to determine clinical course and safety of spontaneous detachment (i.e., allowing the device to fall off), we conducted a case series of no-flip ShangRing circumcision combined with a randomized controlled trial of removal 7 days postcircumcision versus spontaneous detachment at two health facilities in Kenya. The primary outcome was the safety of the no-flip technique based on moderate and severe adverse events (AEs) during the procedure and through 42-day follow-up. A main secondary outcome was clinical course and safety of spontaneous detachment. Two hundred and thirty males 10 years and older underwent no-flip circumcision; 114 randomized to 7-day removal and 116 to spontaneous detachment. All circumcisions were successfully completed. Overall 5.3% (6/114) of participants in the 7-day group and 1.7% (2/116) in the spontaneous group had an AE; with no differences when compared to the 3% AE rate in historical data from African studies using the original flip technique (P = 0.07 and P = 0.79, respectively). Overall 72.4% (84/116) of participants in the spontaneous group wore the ShangRing until it detached. Among the remaining (27.6%; 32/116), the ring was removed, primarily at the participants' request, due to pain or discomfort. There was no difference in AE rates (P = 0.169), visit day declared healed (P = 0.324), or satisfaction (P = 0.371) between randomization groups. The median time to detachment was 14.0 (IQR: 7-21, range: 5-35) days. The no-flip technique and spontaneous detachment are safe, effective, and acceptable to boys and men 10 years and older. Phimosis and penile adhesions do not limit successful ShangRing circumcision with the no-flip technique.

Self-Gated Late Gadolinium Enhancement at 7T to Image Rats with Reperfused Acute Myocardial Infarction

OBJECTIVE: A failed electrocardiography (ECG)-trigger often leads to a long acquisition time (TA) and deterioration in image quality. The purpose of this study was to evaluate and optimize the technique of self-gated (SG) cardiovascular magnetic resonance (CMR) for cardiac late gadolinium enhancement (LGE) imaging of rats with myocardial infarction/reperfusion. MATERIALS AND METHODS: Cardiovascular magnetic resonance images of 10 rats were obtained using SG-LGE or ECG with respiration double-gating (ECG-RESP-gating) method at 7T to compare differences in image interference and TA between the two methods. A variety of flip angles (FA: 10°–80°) and the number of repetitions (NR: 40, 80, 150, and 300) were investigated to determine optimal scan parameters of SG-LGE technique based on image quality score and contrast-to-noise ratio (CNR). RESULTS: Self-gated late gadolinium enhancement allowed successful scan in 10 (100%) rats. However, only 4 (40%) rats were successfully scanned with the ECG-RESP-gating method. TAs with SG-LGE varied depending on NR used (TA: 41, 82, 154, and 307 seconds, corresponding to NR of 40, 80, 150, and 300, respectively). For the ECG-RESP-gating method, the average TA was 220 seconds. For SG-LGE images, CNR (42.5 ± 5.5, 43.5 ± 7.5, 54 ± 9, 59.5 ± 8.5, 56 ± 13, 54 ± 8, and 41 ± 9) and image quality score (1.85 ± 0.75, 2.20 ± 0.83, 2.85 ± 0.37, 3.85 ± 0.52, 2.8 ± 0.51, 2.45 ± 0.76, and 1.95 ± 0.60) were achieved with different FAs (10°, 15°, 20°, 25°, 30°, 35°, and 40°, respectively). Optimal FAs of 20°–30° and NR of 80 were recommended. CONCLUSION: Self-gated technique can improve image quality of LGE without irregular ECG or respiration gating. Therefore, SG-LGE can be used an alternative method of ECG-RESP-gating.

Treatment of sternal infection after cardiac surgery with pectoralis major muscle flap plasty in 247 cases / 中华胸心血管外科杂志

Objective To summarize the experience on the treatment of sternal infection after cardiac surgery,introduce the pectoralis major myocutaneous flap plasty.Methods The clinical data of 247 patients with sternal infection after cardiac surgery in our hospital from January 2014 to July 2017 were retrospectively analyzed.Including 176 males and 71 females,aged from 3 months to 92 years old(162 cases over 60 years old).Results 4 cases died postoperation.226 cases with stage Ⅰ healing,17 cases with stage Ⅱ healing(4 cases of tuberculosis infection cured by anti-tuberculosis treatment).201 cases were followed up,7 cases wound infection relapsed(6 cases with replacement of aortic dissection with artificial blood vessel,and 1 with congenital heart disease).The others had no recurrence.Conclusion The pectoralis major muscle flap inversion plasty for treatment of the median sternal and mediastinal chest incision infection after cardiac surgery can effectively cure the wound,shorten the treatment time,and prevent the secondary complications caused by wound infection.Most patients can obtain primary healing.

Expression and significance of c-FLIP protein in sepsis mice with acute kidney injury / 中华危重病急救医学

Objective To observe the expression of cellular Fas-associated death domain-like interleukin-1β converting enzyme inhibit protein (c-FLIP) in sepsis mice with acute kidney injury (SAKI) and explore its significance. Methods Thirty male ICR mice were divided into the normal control group (Normal group), sham operation group (Sham group) and SAKI group by random number table method, with 10 mice in each group. The SAKI model of mice was established by cecal ligation and puncture (CLP); the Sham group was not ligated and the cecum was not punctured, and other surgical procedures were the same as the SAKI group; the Normal group did not experience any treatment. The serum and renal tissues of mice in each group were harvested 24 hours after CLP model establishment. The levels of serum creatinine (SCr) and blood urea nitrogen (BUN) were detected by enzyme linked immunosorbent assay (ELISA). The renal tissues were stained with hematoxylin-eosin (HE), and the pathological changes of renal tissues were observed under light microscope and the severity of injury was determined. The expression of c-FLIP in renal tissues was detected by immunohistochemistry. The expression of c-FLIP, Bax and caspase-3 protein in renal tissue was detected by Western Blot. The correlation between c-FLIP expression and Bax, caspase-3 protein expressions in renal tissues were analyzed by Pearson test. Results In the Normal group and the Sham group, the renal tubular epithelial cells were regular and intact, and no interstitial inflammatory cell infiltration was observed; the renal injury score was both 1.30±0.48; immunohistochemistry showed a large amount of c-FLIP positive expression in renal tubular epithelial cells (IA: 120.20±3.87, 116.70±3.46); Western Blot showed high expression of c-FLIP in renal tissues (c-FLIP/GAPDH: 0.99±0.01, 0.98±0.02), and low expressions of Bax and caspase-3 (Bax/GAPDH: 0.16±0.04, 0.19±0.03, caspase-3/GAPDH: 0.24±0.04, 0.23±0.05). Compared with the Sham group, in the SAKI group, renal tubular epithelial cells were degenerated and necrosis, and a large number of interstitial inflammatory cells infiltrated, the renal injury score was significantly increased (4.60±0.52 vs. 1.30±0.48, P < 0.01); the levels of SCr and BUN were significantly increased [SCr (μmol/L): 193.90±13.54 vs. 24.50±3.78, BUN (mmol/L): 81.60±7.26 vs. 5.20±0.92, both P < 0.01]; the c-FLIP positive cells in renal tissues was significantly reduced (IA: 17.11±0.82 vs. 116.70±3.46, P < 0.01); the expression of c-FLIP protein in renal tissues was significantly decreased (c-FLIP/GAPDH: 0.29±0.03 vs. 0.98±0.02, P < 0.01), while the expressions of Bax and caspase-3 protein were significantly increased (Bax/GAPDH: 0.87±0.06 vs. 0.19±0.03, caspase-3/GAPDH: 0.88±0.07 vs. 0.23±0.05, both P < 0.01]. The correlation analysis showed that the c-FLIP protein was significantly negatively correlated with Bax (r = -0.468, P = 0.029) and caspase-3 protein expressions (r = -0.663, P = 0.004). Conclusions The expression level of c-FLIP protein was significantly down-regulated in renal tissue of SAKI, and its down-regulation mechanism was associated with increased apoptosis of renal tubular epithelial cells, which could be an effective target for the treatment of SAKI.

Expression and clinical significance of TRAIL and c-FLIP in peripheral blood mononuclear cell of patients with rheumatoid arthritis / 中国免疫学杂志

Objective:To analyze the expression of TNF-related apoptosis-inducing factor TRAIL,c-FLIP and caspase-8 in peripheral blood mononuclear cells of patients with rheumatoid arthritis at different period,in order to provide a experimental basis that treating and looking for a more effective way and method.Methods:mRNA expression of TRAIL,c-FLIP and caspase-8 were detected by Real-time PCR from peripheral blood mononuclear cells;TRAIL,c-FLIP and caspase-8 were checked by Western blot from peripheral blood mononuclear cells.Results:The mRNA expression level of TRAIL,c-FLIP and caspase-8 from PBMC at different groups of RA:TRAIL mRNA in group M was 3.26±0.78 which was much higher than healthy controls(1.30±0.20) (P=0.028),and those of group L and group H (1.56±0.37 and 1.83±0.26 respectively) was slightly higher than controls(P<0.05).C-FLIP mRNA in low activity group (L),middle activity group (M) and high activity group (H) were 1.27±0.28,1.32±0.34 and 1.93±0.40 re-spectively,which was higher than that of healthy controls (1.08 ± 0.12) (P=0.035,0.034,0.030).The relative level caspase-8 mRNA in group L,group M,group H were(2.77 ±0.97),(4.52 ± 0.85),and(2.13 ± 0.44)which was higher than healthy controls (1.04±0.13) (P=0.023,0.012,0.032).The protein level of TRAIL,c-FLIP and caspase-8 in PBMC from different groups of RA patients:The expression of TRAIL in group M was significantly increased than group L,H and control(P<0.05) with no difference in group L.c-FLIP protein in all protein expressed in group M quantity highest,significantly higher than other groups.Caspase-8 expression in the group M and H was significantly enhanced than control (P=0.003,0.001 ) with no difference in group L (P> 0.05). Conclusion:During the different active stages of RA,in peripheral blood mononuclear cells,the expression of TRAIL,c-FLIP and caspase-8 are increased overall trend,possible can provide certain experimental reference for clinical therapy.

CRT promoted c-FLIP expression via NF-κB pathway in rheumatoid arthritis fibroblast-like synoviocytes / 天津医药

Objective To investigate the molecular mechanisms of upregulated expression of cellular Fas-associated death domain-like interleukin-1 beta converting enzyme inhibitory protein(c-FLIP)by calreticulin(CRT)in patients with rheumatoid arthritis (RA). Methods The semi-quantitative analysis and localization of c-FLIP in RA and osteoarthritis (OA)synovium were detected by immunohistochemistry.The fibroblast-like synoviocytes(FLS)were isolated by enzymatic digestion of synovial tissue specimens obtained from RA and OA patients,and cultured as an in vitro experiment model.The expressions of c-FLIP in RA and OA synovial fibroblasts were detected by immunofluorescence and Western blot assay. Whether CRT influenced c-FLIP expression and its molecular mechanism were explored by Western blot assay. Results The high expression of c-FLIP was found in RA synovium, mainly in the lining and sublining areas of FLS and vascular endothelial cells detected by immunohistochemistry.Meanwhile,weak staining of c-FLIP was observed in OA synovium.The expression of c-FLIP was significantly higher in RA synovium than that of OA synovium(t=11.717,P<0.001).Results of immunofluorescence and Western blot assay showed that c-FLIP was mainly located in cytoplasm, and which was higher expressed in FLS of RA than that of OA. The increased c-FLIP expression and phosphorylation of NF-κB were detected after being co-incubated with exogenous CRT (0, 10, 50, 100 μg/L), in dose-dependent manner. The effect of CRT upregulating c-FLIP expression was blocked by NF-κB inhibitor BAY 11-7082.Conclusion CRT can increase c-FLIP expression at least partly through NF-κB pathway in RA,which may provide therapeutic target for the treatment of RA.

Teaching Design and Application of Medical Ethics Based on Flipped Classroom Teaching Model / 中国医学伦理学

The flip classroom,as a new teaching form,has innovated the traditional teaching model.Although the flip classroom has its superiority,it will encounterchallenges in practice.This paper firstly analyzed the feasibility and necessity of medical ethics education based on the flip classroom.Then,it introduced the teaching model of medical ethics flip classroom based on three aspects:the basic pattern design,learning resources design and teaching process design.Finally,it discussed the application and effects of the flip classroom on the teaching of medical ethics.

Diagnosis of Nerve Root Compromise of the Lumbar Spine: Evaluation of the Performance of Three-dimensional Isotropic T2-weighted Turbo Spin-Echo SPACE Sequence at 3T

OBJECTIVE: To explore the performance of three-dimensional (3D) isotropic T2-weighted turbo spin-echo (TSE) sampling perfection with application optimized contrasts using different flip angle evolution (SPACE) sequence on a 3T system, for the evaluation of nerve root compromise by disc herniation or stenosis from central to extraforaminal location of the lumbar spine, when used alone or in combination with conventional two-dimensional (2D) TSE sequence. MATERIALS AND METHODS: Thirty-seven patients who had undergone 3T spine MRI including 2D and 3D sequences, and had subsequent spine surgery for nerve root compromise at a total of 39 nerve levels, were analyzed. A total of 78 nerve roots (48 symptomatic and 30 asymptomatic sites) were graded (0 to 3) using different MRI sets of 2D, 3D (axial plus sagittal), 3D (all planes), and combination of 2D and 3D sequences, with respect to the nerve root compromise caused by posterior disc herniations, lateral recess stenoses, neural foraminal stenoses, or extraforaminal disc herniations; grading was done independently by two readers. Diagnostic performance was compared between different imaging sets using the receiver operating characteristics (ROC) curve analysis. RESULTS: There were no statistically significant differences (p = 0.203 to > 0.999) in the ROC curve area between the imaging sets for both readers 1 and 2, except for combined 2D and 3D (0.843) vs. 2D (0.802) for reader 1 (p = 0.035), and combined 2D and 3D (0.820) vs. 3D including all planes (0.765) for reader 2 (p = 0.049). CONCLUSION: The performance of 3D isotropic T2-weighted TSE sequence of the lumbar spine, whether axial plus sagittal images, or all planes of images, was not significantly different from that of 2D TSE sequences, for the evaluation of nerve root compromise of the lumbar spine. Combining 2D and 3D might possibly improve the diagnostic accuracy compared with either one.

Comparison of the diagnostic value of double echo steady state sequences with 30°and 90° flig angle for knee articular cartilage damage / 实用放射学杂志

Objective To compare the diagnostic accuracy of 3D-DESS sequences with 30°and 90°flip angles for the knee articular cartilage injury (≥Grade 2).Methods Images of 13 patients (2 men,1 1 women,age range 18-68 years)of the knee articular carti-lage injury were obtained with 3D-DESS flip angles of 30°and 90°at 1.5T MR.Two radiologists classified the presence or absence of cartilage damage of ≥Grade 2 as positive (P)or

L-carnitine sensitizes human glioblastoma cells to TRAIL-induced apoptosis / 中国药理学通报

Aim To investigate the enhancing effect of L-carnitine as a sensitizer on tumor necrosis factor-re-lated apoptosis inducing ligand ( TRAIL)-induced ap-optosis in glioma cells. Methods Glioma cell U87 was used as model cell line. Cell viability was determined by CCK-8 , and apoptosis was assessed by Annexin V-FITC/PI staining, caspase-3 activity and expres-sion. The expression and transcription of nuclear factor kappa B ( NF-κB ) and FLICE inhibiting protein ( c-FLIP) were measured by RT-PCR and Western blot. In addition, NF-κB was knockdown to analyze its regu-lating effect on c-FLIP expression. Results The com-bination treatment with TRAIL and L-carnitine signifi-cantly inhibited cell proliferation and induced apopto-sis. Compared with control, combinational treatment significantly suppressed the transcription and expres-sion of c-FLIP as well as translocation of NF-κB. Through silencing NF-κB, NF-κB was found to act as upstream signaling to regulate c-FLIP. Conclusion L-carnitine sensitizes TRAIL-induced tumor cell apoptosis via suppression of NF-κB-dependent c-FLIP expres-sion.

Unstable posterior acetabular fractures: Early results of delayed reduction and fracture fixation using the Kocher-Langenbeck approach with trochanteric flip osteotomy

@#<p style="text-align: justify;">Unstable posterior acetabular fractures resulting from high energy trauma present major challenges to any orthopedic surgeon especially if the treatment has been delayed.<br /><strong>OBJECTIVE:</strong> The purpose of this paper is to describe the early results of delayed treatment of a series of patients with posterior acetabular fractures with concomitant hip dislocations, surgically approached using the Kocher-Langenbeck with a trochanteric flip osteotomy.<br /><strong>METHODS:</strong> Five (5) male patients (mean age 35.6 years, range 23-58 years) who sustained unstable posterior acetabular fractures, underwent surgical treatment using the Kocher-Langenbeck approach with the trochanteric flip osteotomy, during the period of May 2014 to October 2015. Clinical and radiographic evaluations of each patient were performed, while complications were documented.<br /><strong>RESULTS:</strong> Mean follow-up was 8 weeks (range 2-12 weeks). There was adequate exposure of the posterior and superior acetabulum in all patients. Post-operative radiographs in four of five patients were graded "anatomic" while hip range of motion of these four patients averaged 78.7% of the uninjured hip. One patient with "poor" reduction underwent a second operation to reserve a failure of the initial fixation using the same surgical approach. No other complications were reported.<br /><strong>CONCLUSION:</strong> This modified approach provides adequate exposure of both posterior and superior acetabulum and also allows inspection of the articular surfaces of both acetabulum and femoral head, which are limited in the standard Kocher-Lagenbeck approach. With excellent exposure, congruent reduction can readily be achieved while permitting early hip range of motion post-surgery.</p>

The Histone Deacetylase Inhibitor Trichostatin A Sensitizes Human Renal Carcinoma Cells to TRAIL-Induced Apoptosis through Down-Regulation of c-FLIP(L)

Histone acetylation plays a critical role in the regulation of transcription by altering the structure of chromatin, and it may influence the resistance of some tumor cells to tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) by regulating the gene expression of components of the TRAIL signaling pathway. In this study, we investigated the effects and molecular mechanisms of trichostatin A (TSA), a histone deacetylase inhibitor, in sensitizing TRAIL-induced apoptosis in Caki human renal carcinoma cells. Our results indicate that nontoxic concentrations of TSA substantially enhance TRAIL-induced apoptosis compared with treatment with either agent alone. Cotreatment with TSA and TRAIL effectively induced cleavage of Bid and loss of mitochondrial membrane potential (MMP), which was associated with the activation of caspases (-3, -8, and -9) and degradation of poly (ADP-ribose) polymerase (PARP), contributing toward the sensitization to TRAIL. Combined treatment with TSA and TRAIL significantly reduced the levels of the cellular Fas-associated death domain (FADD)-like interleukin-1beta-converting enzyme (FLICE) inhibitory protein (c-FLIP), whereas those of death receptor (DR) 4, DR5, and FADD remained unchanged. The synergistic effect of TAS and TRAIL was perfectly attenuated in c-FLIP(L)-overexpressing Caki cells. Taken together, the present study demonstrates that down-regulation of c-FLIP contributes to TSA-facilitated TRAIL-induced apoptosis, amplifying the death receptor, as well as mitochondria-mediated apoptotic signaling pathways.

Relationship between c-FLIP protein and drug resistance of ovarian cancer cells to TRAIL-induced apoptosis / 西安交通大学学报(医学版)

Objective To explore the mechanism of drug resistance of ovarian cancer cells to TRAIL-induced apoptosis.Methods We collected 3AO cells and CAOV3 cells,respectively,at 18,24,48 and 72 hour under 12.5,25,50 and 100 ng/mL concentrations of TRAIL.The rate of cell growth inhibition was checked by methyl thiazolyl tetrazolium (MTT)assay to evaluate the effect of TRAIL.Morphology of apoptotic cells was observed by TdT-mediated-dUTP nick end labeling (TUNEL).The apoptosis rate was detected by flow cytometry (FCM)and C-FLIP protein was determined by Western blotting.Results TRAIL inhibited the growth of 3AO and CAOV3 cells.The rate of growth inhibition at 24 hour was 28% in 3AO cells and 10% in CAOV3 cells.TRAIL induced apoptosis of cells.The apoptosis rate at 24 hour was 8.5% in 3AO cells,which was higher than 5.5% in CAOV3 cells.The expression level of C-FLIP protein was higher in CAOV3 cells than in 3AO cells.Conclusion C-FLIP protein is an important protein that regulates drug resistance of ovarian cancer cells to TRAIL-induced apoptosis.

Studies on cell death and survival regulatory protein c-FLIP as a target for cancer treatment / 中国药理学通报

Many tumor cells are resistant to cell apoptosis through the expression of antiapoptotic proteins. c-FLIP is a ma-jor resistance protein of antiapoptosis. In human cells, there are three types of c-FLIP, c-FLIPL , c-FLIPS and c-FLIPR . The c-FLIP binds to FADD to prevent the formation of procaspase-8-DISC and the subsequent activation of caspase cascade. Further-more, c-FLIPL and c-FLIPS have multifunctional roles in various cellular signaling pathways, as well as up-regulating several cyto-protective signaling. Studies show that upregulation of c-FLIP has been found in various tumors, and its downregulation has been shown to restore apoptosis triggered by various chemothera-peutic agents, like the transcriptional regulating agents, trichos-tatin-A, camptothecin, cisplatin, doxorubicin, etc. or other new biotechnologies, such as the specific siRNA. Therefore, c-FLIPS are important targets of cancer therapy. This review summarizes the results on the role of c-FLIP in cancer chemotherapy of tradi-tional antitumor agents and siRNA, and to provide new ideas and rationales of searching for the antiapoptosis effective compounds that can specifically antagonize c-FLIP.