Quality control of postoperative radiotherapy for non-small cell lung cancer: A study of mediastinal shift.

PURPOSE: This study aimed to assess the shifting patterns of the mediastinum, including the target volume and the isocenter point during the postoperative radiotherapy (PORT) process of non-small cell lung cancer (NSCLC), and to observe the occurrence of radiation injury. Additionally, we investigated the significance of mid-term assessment during the implementation of the PORT process. MATERIAL AND METHODS: We established coordinate axes based on bone anatomy and measured the mediastinum's three-dimensional direction and the shift of the isocenter point's shift in the PORT process. Statistical analysis was performed using Wilcoxon, Kruskal-Wallis, and the Chi-square test. P<0.05 was considered statistically significant. RESULTS: In this study, the analysis of patients revealed that the shift of anterior and posterior mediastinum (X), left and right mediastinum (Y), upper and lower mediastinum (Z), anterior and posterior isocenter point (Xi), and the left and right isocenter points (Yi) in the PORT process were 0.04-0.53, 0.00-0.84, 0.00-1.27, 0.01-0.86, and 0.00-0.66cm, respectively. The shift distance of the mediastinum was Z>Y>X, and the shift distance of the isocenter point was Xi>Yi. According to the ROC curve, the cut-off values were 0.263, 0.352, 0.405, 0.238, and 0.258, respectively, which were more significant than the cut-off values in 25 cases (25%), 30 cases (30%), 30 cases (30%), 17 cases (17%), and 15 cases (15%). In addition, there was a significant difference in the shift of the mediastinum and the isocenter point (all P=0.00). Kruskal-Wallis test showed no statistically significant difference between mediastinal shift and resection site in X, Y, and Z directions (P=0.355, P=0.239, P=0.256), surgical method (P=0.241, P=0.110, P=0.064). There was no significant difference in the incidence of RE and RP in PORT patients (P>0.05). No III-IV RP occurred. However, the incidence of ≥ grade III RE in the modified plan cases after M-S was significantly lower than in the original PORT patients, 0% and 7%, respectively (P=0.000). CONCLUSION: In conclusion, this study provides evidence that mediastinal shift is a potential complication during the PORT process for patients with N2 stage or R1-2 resection following radical resection of NSCLC. This shift affects about 20-30% of patients, manifesting as actual radiation damage to normal tissue and reducing the local control rate. Therefore, mid-term repositioning of the PORT and revision of the target volume and radiation therapy plan can aid in maintaining QA and QC during the treatment of NSCLC patients and may result in improved patient outcomes.

[Clinical and genotypic analysis of hereditary spherocytosis combined with cholestasis among pediatric patients].

Objective: To understand the clinical and genetic characteristics of hereditary spherocytosis (HS) combined with cholestasis among pediatric patients. Methods: 12 cases of HS children accompanied by cholestasis at Hunan Children's Hospital were selected as the research subjects between January 2013 and December 2022. Clinical data were collected. Whole-exome sequencing was performed by second-generation sequencing. Suspected pathogenic mutation sites were verified by Sanger sequencing. Results: All pediatric patients were admitted to the hospital due to their yellow skin tone. Eight cases (66.67%) had a positive family history. The clinical manifestations were jaundice, splenomegaly (12/12), abdominal pain, anemia (4/12), and hepatomegaly (5/12). All pediatric patients had decreased hemoglobin, an increased reticulocyte ratio, total bilirubin and direct bilirubin, a positive erythrocyte fragility test, and remarkable spherical erythrocytes in their peripheral blood. Seven cases had elevated aminotransferase; four cases had severely elevated aminotransferase and bilirubin; eight cases had biliary calculi; and two cases had a dilated biliary tract. Liver pathological examination showed mild damage to the liver cells (G1S1) in three pediatric cases. Five children had a total of six unreported mutations: SPTB gene c.2431_2450del, c.4974-2A > G, c.2575G > A, and exon 22-35 deletion; ANK1 gene: c.2379-2380delC; and c .6dupC. Children still had abnormal bilirubin levels following treatment. Two pediatric cases underwent splenectomy. Bilirubin and hemoglobin levels returned to normal after surgery. Conclusion: Children with HS may experience cholestasis, and those with poor treatment results may consider undergoing a splenectomy. Six new types of variants have expanded the HS gene mutation spectrum.

[Impact of the depth of remission by induction chemotherapy on the prognosis of limited stage small cell lung cancer].

Objective: To evaluate the effect of depth of remission of induction chemotherapy on the overall prognosis of limited stage small cell lung cancer (L-SCLC). Methods: The study was a retrospective, L-SCLC patients who contained complete imaging data and underwent consecutive standardized treatments at the Department of Thoracic Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University between January 2013 and June 2021 were included. To delineate the volume of tumor before and after induction chemotherapy and to calculate the depth of remission caused by the induced chemotherapy. The time receiver operating characteristic (timeROC) method was used to determine the optimal predictors for prognosis, multi-factor analysis using Cox risk proportional model. Results: A total of 104 patients were included in this study. The median PFS and OS of this cohort were 13.7 months and 20.9 months, respectively. It was observed by timeROC analysis that residual tumor volume after induction chemotherapy had the optimal predictive value of PFS at 1 year (AUC=0.86, 95% CI: 0.78~0.94) and OS at 2 years (AUC=0.76, 95% CI: 0.65~0.87). Multivariate analysis showed residual tumor volume after induction chemotherapy was the independent prognostic factor to PFS (HR=1.006, 95% CI: 1.003~1.009, P<0.01) and OS (HR=1.009, 95% CI: 1.005~1.012, P<0.001). For those whose residual tumor volume remitted to less than 10 cm(3) after induction chemotherapy, the favorable long-term outcomes could be achieved, regardless of their initial tumor load. Conclusion: The depth of remission of induction chemotherapy could be a promising prognostic predictor to the L-SCLC and provide the individualized treatment guidance.

[Clinical analysis of re-operative management for residual partial anomalous pulmonary venous connection after previous cardiac surgery].

Objectives: To analyze the reasons of residual partial anomalous pulmonary venous connection (PAPVC) after previous cardiac surgery, and summarize the strategies and experience for diagnosis and treatment of secondary correction operation. Methods: The clinical data of 18 patients who were admitted to Fuwai Hospital of Chinese Academy of Medical Sciences and Fuwai Yunnan Cardiovascular Hospital from June 2009 to May 2019 were retrospectively analyzed. All the patients underwent secondary cardiac surgery to treat PAPVC. The preoperative and intraoperative characteristics and postoperative complications of the patients were summarized and analyzed. Results: Totally, there were 7 male and 11 female cases, aged 1-49 years (median age: 4.5 years). In the first cardiac surgery, 3 patients were diagnosed with PAPVC, which existed after surgery. One patient was diagnosed with total anomalous pulmonary venous connection (TAPVC), but left PAPVC after surgery. The remaining 14 patients were all missed preoperative and intraoperative diagnosis. After the initial surgery, most patients had no significant symptoms (11/18), but PAPVC was found in 11 cases due to postoperative cardiac murmur or transthoracic echocardiography (TTE). In the secondary surgery, there were 4 cases of type A, 10 cases of type B, 2 cases of type C, no type D, and 2 cases of mixed type, respectively, according to Bordy classification. The diagnostic accuracy of TTE and CT angiography (CTA) was 50.0% and 92.9%, respectively. There was no death after the second surgery, but pulmonary vein occlusion, pericardial effusion, anastomotic stenosis and other complications occurred in 4 patients. Conclusions: The main causes of missed diagnosis of PAPVC are the undefined cardiac structural deformities before operation and the lack of careful exploration during the operation. TTE is simple and feasible to diagnose PAPVC, and it can improve the diagnostic accuracy when combined with CTA.

[Outcomes and the role of adjuvant therapy of limited stage small cell lung cancer undergoing surgical treatment].

Objective: To investigate the outcomes of limited stage small cell lung cancer (L-SCLC) undergoing surgical therapy and to explore the value of adjuvant therapy for those patients. Methods: A retrospective analysis was initialed for the L-SCLC patients who underwent the surgical treatment in the Zhongnan Hospital of Wuhan University from January 2012 to December 2018. The median disease-free survival (DFS) and overall survival (OS) were calculated by Kaplan-Meier method. Cox regression was used to explore the prognostic factors. Results: A total of 44 patients were included in our study. The median DFS was 25 months, 1- and 2-year DFS rate were 70.2% and 51.9%, respectively. The median OS was 41 months, 1- and 2- year OS rate were 88.4% and 69.9%, respectively. Multivariate analysis showed male (RR=6.56, P=0.03), T3-4 (RR=6.23, P=0.01), pathological lymph node metastasis (RR=6.52, P=0.03) and adjuvant radiotherapy (RR=0.13, P=0.002) were associated with disease relapse significantly. Moreover, pathological lymph node metastasis (RR=3.62, P=0.01) coupled with sufficient adjuvant chemotherapy (≥4 cycles) (RR=0.12, P=0.01) were independent prognostic factors of OS. Conclusions: Surgical therapy may be an alternative primary treatment for L-SCLC. Additional adjuvant radiotherapy can reduce the risk of recurrence. Giving sufficient course of adjuvant chemotherapy can improve OS.

[Safety and efficacy of percutaneous intervention for children with combined congenital heart abnormality solely guided by transthoracic echocardiography].

Objective: To investigate the safety and efficacy of percutaneous intervention of children with combined congenital heart abnormality solely guided by transthoracic echocardiography (TTE) . Methods: From September 2015 to June 2017, 21 children with combined congenital heart abnormality undergoing percutaneous interventional guided by TTE in Fuwai hospital were enrolled in our study, and the clinical data were retrospective analyzed. The atrial septal defect(ASD) closure, ventricular septal defect(VSD) closure, patent ductus arteriosus(PDA) closure or balloon pulmonary valvuloplasty were performed under the guidance of TTE. The procedural effect was evaluated by TTE after operation. The patients were followed up after discharged from the hospital. Results: The age was (37.3±11.6) months, and there were 9 male and 12 female patients. There were 4 cases with ASD and VSD, 6 cases with VSD and PDA, 6 cases with ASD and PDA, 2 cases with VSD and pulmonary stenosis, 3 cases with ASD and pulmonary stenosis. The operations were successfully performed in all patients. No one required extra X ray guidance or open heart surgery. The operation time was (44.6±7.5)min. All patients did not require blood transfusion, inotropic support, and analgesia. There were no complications such as peripheral vascular injury and pericardialeffusion after the operation. The length of hospital stay time was (3.5±0.6) days. All patients were recovered well. The follow-up was (17.6±5.2) months, and post-procedural conduction disturbances, residual shunts, occlude fall off, thrombosis, and new onset of valvular regurgitation were not observed in these patients. Conclusion: Percutaneous interventional of children with combined congenital heart abnormality solely guided by TTE is safe and effective, and the procedure can avoid the potential injuries of X ray and contrast agent.

[Comparison of transthoracic or percutaneous balloon pulmonary valvuloplasty in the therapy of pulmonary valve stenosis].

Objective: To compare the clinical outcome of patients with pulmonary valve stenosis underwent transthoracic and percutaneous balloon pulmonary valvuloplasty. Methods: Clinical data of 806 patients diagnosed as pulmonary valve stenosis underwent transthoracic(171 patients as group A)or percutaneous balloon pulmonary valvuloplasty (635 patients as Group B) in Fuwai Hospital from February 2006 to January 2016 were analyzed retrospectively. There were 72 males in group A (42.1%) and 344 males in group B (54.2%). The average age was (1.6±1.1) years in group A and (21.0±18.5) years in group B. The median weight was 7.65 (7.68) kg (M(Q(R))) in group A and 43.75 (47.38) kg in group B. There were 732 (90.9%) patients followed up from 3 months to 10 years, with an average interval of (6.3±3.6) years. Sixty cases were ligated patent ductus arteriosus simultaneously, and 20 cases got Blalock-Taussig shunt at the same time of valvuloplasty in group A. There were 47 cases of transcatheter closure of atrial septal defect and 6 cases of transcatheter closure of patent ductus arteriosus in group B. The t test, rank sum test and χ(2) test were used to compare data of two groups. Results: There were no hospital death or cardiac tamponade and other serious complications for all patients. The postoperative hospital stayin group A was significantly longer than that in group B (8(5) days vs. 2(2) days, Z=-9.404, P=0.000). In every further consultation, patients were reviewed with transthoracic echocardiography to assess transpulmonary gradient and pulmonary regurgitation. There were significant difference between group A and B of preoperative transpulmonary pressure gradient ((80.6±22.4) mmHg vs.(72.6±20.5) mmHg, t=1.611, P=0.032, 1 mmHg=0.133 kPa) and so as transpulmonary pressure gradient reduction value ((55.9±21.0) mmHg vs. (46.6±23.4) mmHg, t=-1.710, P=0.026). Patients in both groups had good cardiac function during follow-up interval. One patient needed surgical valvuloplasty 10 months after percutaneous balloon pulmonary valvuloplasty and 1 case occurred moderate to severe tricuspid regurgitation in group B. During follow-up period, there was no significant difference between group A and B of transpulmonary pressure gradient ((22.3±6.5) mmHg vs. (25.2±12.6) mmHg, t=1.320, P=0.072), the incidence of pulmonary valve regurgitation in patients of group A was significantly lower than patients of group B (56.1% vs.65.2%, χ(2)=4.755, P=0.029). Conclusions: The clinical outcome and complications are similar between patients underwent two different routes of balloon pulmonary valvuloplasty. Transthoracic balloon pulmonary valvuloplasty is more suitable for infant and underweight children patients with pulmonary valve stenosis. Percutaneous balloon pulmonary valvuloplasty is more suitable for the treatment of the elder children or adults.

Activity-dependent depression of neuronal sodium channels by the general anaesthetic isoflurane.

BACKGROUND: The mechanisms by which volatile anaesthetics such as isoflurane alter neuronal function are poorly understood, in particular their presynaptic mechanisms. Presynaptic voltage-gated sodium channels (Na(v)) have been implicated as a target for anaesthetic inhibition of neurotransmitter release. We hypothesize that state-dependent interactions of isoflurane with Na(v) lead to increased inhibition of Na(+) current (I(Na)) during periods of high-frequency neuronal activity. METHODS: The electrophysiological effects of isoflurane, at concentrations equivalent to those used clinically, were measured on recombinant brain-type Na(v)1.2 expressed in ND7/23 neuroblastoma cells and on endogenous Na(v) in isolated rat neurohypophysial nerve terminals. Rate constants determined from experiments on the recombinant channel were used in a simple model of Na(v) gating. RESULTS: At resting membrane potentials, isoflurane depressed peak I(Na) and shifted steady-state inactivation in a hyperpolarizing direction. After membrane depolarization, isoflurane accelerated entry (τ(control)=0.36 [0.03] ms compared with τ(isoflurane)=0.33 [0.05] ms, P<0.05) and slowed recovery (τ(control)=6.9 [1.1] ms compared with τ(isoflurane)=9.0 [1.9] ms, P<0.005) from apparent fast inactivation, resulting in enhanced depression of I(Na), during high-frequency stimulation of both recombinant and endogenous nerve terminal Na(v). A simple model of Na(v) gating involving stabilisation of fast inactivation, accounts for this novel form of activity-dependent block. CONCLUSIONS: Isoflurane stabilises the fast-inactivated state of neuronal Na(v) leading to greater depression of I(Na) during high-frequency stimulation, consistent with enhanced inhibition of fast firing neurones.

Global microRNA profiles and signaling pathways in the development of cardiac hypertrophy

Hypertrophy is a major predictor of progressive heart disease and has an adverse prognosis. MicroRNAs (miRNAs) that accumulate during the course of cardiac hypertrophy may participate in the process. However, the nature of any interaction between a hypertrophy-specific signaling pathway and aberrant expression of miRNAs remains unclear. In this study, Spague Dawley male rats were treated with transverse aortic constriction (TAC) surgery to mimic pathological hypertrophy. Hearts were isolated from TAC and sham operated rats (n=5 for each group at 5, 10, 15, and 20 days after surgery) for miRNA microarray assay. The miRNAs dysexpressed during hypertrophy were further analyzed using a combination of bioinformatics algorithms in order to predict possible targets. Increased expression of the target genes identified in diverse signaling pathways was also analyzed. Two sets of miRNAs were identified, showing different expression patterns during hypertrophy. Bioinformatics analysis suggested the miRNAs may regulate multiple hypertrophy-specific signaling pathways by targeting the member genes and the interaction of miRNA and mRNA might form a network that leads to cardiac hypertrophy. In addition, the multifold changes in several miRNAs suggested that upregulation of rno-miR-331*, rno-miR-3596b, rno-miR-3557-5p and downregulation of rno-miR-10a, miR-221, miR-190, miR-451 could be seen as biomarkers of prognosis in clinical therapy of heart failure. This study described, for the first time, a potential mechanism of cardiac hypertrophy involving multiple signaling pathways that control up- and downregulation of miRNAs. It represents a first step in the systematic discovery of miRNA function in cardiovascular hypertrophy.

Serum high-mobility group box 1 protein correlates with cognitive decline after gastrointestinal surgery.

BACKGROUND: Accumulating evidence has indicated that inflammation may act as a potential mechanism underlying post-operative cognitive dysfunction (POCD). High-mobility group box 1 (HMGB1), as a known late mediator of inflammation, is involved in the development of post-operative complications. Thus, we sought to determine the role of HMGB1 in reflecting POCD following major gastrointestinal surgery. METHODS: Fifty-three elderly patients undergoing gastrointestinal surgery were recruited, and 50 patients completed the study. Serum HMGB1 and interleukin (IL)-6 levels were measured pre-operatively and at 6 h, day 1 and day 3 post-operatively. Neuropsychological tests were administered before and 1 week after surgery. POCD was determined using a Z score ≥ 1.96. RESULTS: Seventeen (34%, 17/50) patients developed POCD at 1 week. The POCD group had higher serum HMGB1 levels at day 1 (12.15 ± 3.12 vs. 9.91 ± 3.15 ng/ml, P = 0.021) and day 3 (11.04 ± 2.88 vs. 8.52 ± 3.31 ng/ml, P = 0.011). IL-6 levels at 6 h (51.18 ± 15.22 vs. 39.20 ± 14.32 pg/ml, P = 0.009) and day 1 (41.59 ± 11.08 vs. 33.81 ± 11.42 pg/ml, P = 0.026) were significantly higher in POCD patients. Serum values of IL-6 at 6 h, HMGB1 at day 1 and levels of education showed positive correlations with Z scores. HMGB1 at day 3 and IL-6 at 6 h were independent risk factors. CONCLUSIONS: Serum HMGB1 and IL-6 levels increase significantly after major gastrointestinal surgery in elderly patients and such elevations are associated with the occurrence of cognitive decline after surgery.

Global microRNA profiles and signaling pathways in the development of cardiac hypertrophy.

Hypertrophy is a major predictor of progressive heart disease and has an adverse prognosis. MicroRNAs (miRNAs) that accumulate during the course of cardiac hypertrophy may participate in the process. However, the nature of any interaction between a hypertrophy-specific signaling pathway and aberrant expression of miRNAs remains unclear. In this study, Spague Dawley male rats were treated with transverse aortic constriction (TAC) surgery to mimic pathological hypertrophy. Hearts were isolated from TAC and sham operated rats (n=5 for each group at 5, 10, 15, and 20 days after surgery) for miRNA microarray assay. The miRNAs dysexpressed during hypertrophy were further analyzed using a combination of bioinformatics algorithms in order to predict possible targets. Increased expression of the target genes identified in diverse signaling pathways was also analyzed. Two sets of miRNAs were identified, showing different expression patterns during hypertrophy. Bioinformatics analysis suggested the miRNAs may regulate multiple hypertrophy-specific signaling pathways by targeting the member genes and the interaction of miRNA and mRNA might form a network that leads to cardiac hypertrophy. In addition, the multifold changes in several miRNAs suggested that upregulation of rno-miR-331*, rno-miR-3596b, rno-miR-3557-5p and downregulation of rno-miR-10a, miR-221, miR-190, miR-451 could be seen as biomarkers of prognosis in clinical therapy of heart failure. This study described, for the first time, a potential mechanism of cardiac hypertrophy involving multiple signaling pathways that control up- and downregulation of miRNAs. It represents a first step in the systematic discovery of miRNA function in cardiovascular hypertrophy.

Regulatory T cells: a possible promising approach to cancer recurrence induced by morphine.

Cancer recurrence is one of the most important causes of cancer-related deaths. In present, it has been revealed that there exist some factors especially opioids being able to affect the recovery of cancer patients in a long period. As the most commonly used potent analgesics in practice, morphine appears to be of crucial importance in the regulation of neoplastic tissues by modulating immune responses and promoting angiogenesis. Indeed, regulatory T cells have been shown to inhibit the response of the immune system to tumor and thereby to worsen prognoses. Some reliable evidences indicate that morphine acts directly on regulatory T cells through VEGFR 2 and opioid receptors present in, both of which play a vital role in the cancer recurrence. In addition, morphine might have a noticeable effect on regulatory T cells by regulating the function of some other immune cells or cytokines, TGF-ß and IL-2 for instance. Thus, this paper speculates that morphine could induce cancer recurrence by disturbing the behavior of the regulatory T cells and provides a logical reasoning.

IL-22 from conventional NK cells is epithelial regenerative and inflammation protective during influenza infection.

Influenza infection primarily targets the upper respiratory system, leading to a severe destruction of the epithelial cell layer. The role of immune cells in the regeneration of tracheal and bronchial epithelial cells is not well defined. Here, we investigated the production of pro-constructive cytokine, Interleukin-22 (IL-22), in the bronchoalveolar lavage (BAL), trachea, lung tissue, and spleen during influenza infection. We found that conventional natural killer (NK) cells (NCR1(+)NK1.1(+)CD127(-)RORγt(-)) were the predominant IL-22-producers in the BAL, trachea, and lung tissues. Tracheal epithelial cells constitutively expressed high levels of IL-22R and underwent active proliferation in response to IL-22 in the wild-type mice. Infection of IL-22(-/-) mice with influenza virus resulted in a severe impairment in the regeneration of tracheal epithelial cells. In addition, IL-22(-/-) mice continued to lose body weight even after 10 days post infection without any recovery. Tracheal epithelial cell proliferation was significantly reduced in IL-22(-/-) mice during influenza infection. Adoptive transfer of IL-22-sufficient but not IL-22-deficient NK cells into IL-22(-/-) mice restored the tracheal/bronchial epithelial cell regeneration and conferred protection against inflammation. Our findings strongly suggest that conventional NK cells have evolved to both kill virus-infected cells and also to provide vital cytokines for tissue regeneration.

Cyclooxygenase-2 (COX-2) mediates arsenite inhibition of UVB-induced cellular apoptosis in mouse epidermal Cl41 cells.

Inorganic arsenic is an environmental human carcinogen, and has been shown to act as a co-carcinogen with solar ultraviolet (UV) radiation in mouse skin tumor induction even at low concentrations. However, the precise mechanism of its co-carcinogenic action is largely unknown. Apoptosis plays an essential role as a protective mechanism against neoplastic development in the organism by eliminating genetically damaged cells. Thus, suppression of apoptosis is thought to contribute to carcinogenesis. It is known that cyclooxygenase-2 (COX-2) can promote carcinogenesis by inhibiting cell apoptosis under stress conditions; and our current studies investigated the potential contribution of COX-2 to the inhibitory effect of arsenite in UV-induced cell apoptosis in mouse epidermal Cl41 cells. We found that treatment of cells with low concentration (5 µM) arsenite attenuated cellular apoptosis upon UVB radiation accompanied with a coinductive effect on COX-2 expression and nuclear factor-κB (NFκB) transactivation. Our results also showed that the COX-2 induction by arsenite and UVB depended on an NFκB pathway because COX-2 co-induction could be attenuated in either p65-deficient or p50-deficient cells. Moreover, UVB-induced cell apoptosis could be dramatically reduced by the introduction of exogenous COX-2 expression, whereas the inhibitory effect of arsenite on UVB-induced cell apoptosis could be impaired in COX-2 knockdown C141 cells. Our results indicated that COX-2 mediated the anti-apoptotic effect of arsenite in UVB radiation through an NFκB-dependent pathway. Given the importance of apoptosis evasion during carcinogenesis, we anticipated that COX-2 induction might be at least partially responsible for the co-carcinogenic effect of arsenite on UVB-induced skin carcinogenesis.

Dichroic ATR-FTIR spectroscopy on oriented α-helical poly(l-lysine) multilayered with polyanions.

The preparation and spectroscopic and microscopic characterization of oriented polyelectrolyte multilayers (PEM) interesting for defined nanostructured functional materials and surfaces are reviewed. Oriented PEM were generated by consecutively adsorbing α-helical poly(l-lysine) (PLL) and oppositely charged polyanions like poly(vinylsulfate) (PVS) or poly(styrene sulfonate) (PSS) at silicon substrates texturized by parallel nanoscopic surface grooves, respectively. Dichroic Attenuated Total Reflexion Fourier Transform Infrared (ATR-FTIR) spectroscopy was used to study the conformation and macromolecular order of stiff polyelectrolytes within PEM. High order parameters up to S=0.82 (S=1 for high, S=0 for low order) were obtained from the dichroic ratios of the Amide I and Amide II bands suggesting a significant alignment of charged α-helical polypeptides in PEM. For PEM consisting of PLL/polyanion the S values significantly increased with increasing molecular weight of PLL and with decreasing molecular weight of the polyanion. These spectroscopic findings were supported by SFM images on PEM-PLL/PVS with high molecular PLL and PEM-PLL/PSS with low molecular PSS, which both showed anisotropically oriented worm-like structures, while PEM-PLL/PVS with low molecular PLL and PEM-PLL/PSS with high molecular PSS showed no orientation features.

Enhanced radiosensitivity of SW480 cells via TRAIL up-regulation mediated by Egr-1 promoter.

Radiosensitization of cancer cells to irradiation could improve the efficacy of radiotherapy. The early transcriptional factor (Egr-1) promoter induced expression of downstream genes after irradiation. TNF-related apoptosis-inducing ligand (TRAIL) is known to induce apoptosis in malignant cells, but displayed little or no toxicity on normal cells. In this study, we constructed pcDNA3.1-Egr-1-TRAIL (pEgr.1-TRAIL) recombinant plasmid and evaluated its effect on human colon cancer cell line SW480. pEgr.1-TRAIL transfection combined with radiotherapy caused dramatically elevation of TRAIL expression both in mRNA and protein levels, much lower radiobiological parameters in clonogenic assays, accompanied by remarkably increase in apoptosis ratio. Furthermore, pEgr.1-TRAIL transfected cells displayed higher proportion in G0/G1 phase. Our results suggested that pEgr.1-TRAIL can sensitize SW480 cells to radiation, and the radiosensitization is related to cell cycle changes and apoptosis mediated by up-regulation of TRAIL expression. These findings support the potential future application of genetic radiotherapy against carcinoma.

Association evidence of schizophrenia with distal genomic region of NOTCH4 in Taiwanese families.

Evidence for association with schizophrenia has been reported for NOTCH4, although results have been inconsistent. Previous studies have focused on polymorphisms in the 5' promoter region and first exon of NOTCH4. Our aim was to test the association of the entire genomic region of NOTCH4 in 218 families with at least two siblings affected by schizophrenia in Taiwan. We genotyped seven single nucleotide polymorphisms (SNPs) of this gene, with average intermarker distances of 5.3 kb. Intermarker linkage disequilibrium (LD) was calculated using gold software, and single-locus and haplotype association analyses were performed using transmit software. We found that the T allele of SNP rs2071285 (P= 0.035) and the G allele of SNP rs204993 (P= 0.0097) were significantly preferentially transmitted to the affected individuals in the single-locus association analysis. The two SNPs were in high LD (D' > 0.8). Trend for overtransmission was shown for the T-G haplotype of the two SNPs to affected individuals (P= 0.053), with the A-A haplotype significantly undertransmitted (P= 0.034). The associated region distributed across the distal portion of the NOTCH4 gene and overlapped with the genomic region of the G-protein signaling modulator 3 and pre-B-cell leukemia transcription factor 2. In summary, we found modest association evidence between schizophrenia and the distal genomic region of NOTCH4 in this Taiwanese family sample. Further replication for association with the distal genomic region of NOTCH4 is warranted.

Targeting interferon-alpha: a promising approach for systemic lupus erythematosus therapy.

System lupus erythematosus (SLE) is an autoimmune disease with multicellular pathogeneic components. Recent studies suggest an important role for interferon-alpha (IFN) in the immunopathogenesis of SLE. Data demonstrating a correlation between IFN-alpha and SLE disease severity range from elevated IFN-alpha levels in patients' serum and induction of IFN-regulated genes in peripheral blood mononuclear cells, to drug induced lupus disease in hepatitis C or cancer patients treated with recombinant IFN-alpha. In addition, mouse models of lupus in which the IFNR is deleted fail to develop disease manifestations. Thus, targeting IFN-alpha promises to be therapeutically efficacious for SLE.

Friend of GATA-1 represses GATA-3-dependent activity in CD4+ T cells.

The development of naive CD4+ T cells into a T helper (Th) 2 subset capable of producing interleukin (IL)-4, IL-5, and IL-13 involves a signal transducer and activator of transcription (Stat)6-dependent induction of GATA-3 expression, followed by Stat6-independent GATA-3 autoactivation. The friend of GATA (FOG)-1 protein regulates GATA transcription factor activity in several stages of hematopoietic development including erythrocyte and megakaryocyte differentiation, but whether FOG-1 regulates GATA-3 in T cells is uncertain. We show that FOG-1 can repress GATA-3-dependent activation of the IL-5 promoter in T cells. Also, FOG-1 overexpression during primary activation of naive T cells inhibited Th2 development in CD4+ T cells. FOG-1 fully repressed GATA-3-dependent Th2 development and GATA-3 autoactivation, but not Stat6-dependent induction of GATA-3. FOG-1 overexpression repressed development of Th2 cells from naive T cells, but did not reverse the phenotype of fully committed Th2 cells. Thus, FOG-1 may be one factor capable of regulating the Th2 development.