Association of systemic inflammation and low performance status with reduced survival outcome in older adults with cancer.

BACKGROUND: Inflammation is involved in the progression and prognosis of cancer because it can affect the physical status and prognosis of patients. Among numerous systemic inflammatory markers, the optimal prognostic indicator of older adults with cancer is still unclear. We aimed to identify an ideal inflammatory immune marker in older adults with cancer and assess the survival outcome combined with eastern cooperative oncology group performance status (ECOG PS). METHODS: We included 1767 older adults with cancer (66.2% males, 70.97 ± 5.49 years old) from a prospective cohort study. Fifteen systemic inflammatory biomarkers were compared to identify the optimal biomarker using prognostic area under the curve (AUC) and concordance index (C-index) analysis. The prognostic value of the clinical parameters was elucidated by performing uni- and multivariate analyses. RESULTS: The AUC, C-index, and the subgroup survival analysis of ECOG PS groups showed that the lymphocyte-C reactive protein ratio (LCR) and C-reactive protein/albumin ratio (CAR) were more accurate in reflecting patient prognosis than the other 13 inflammatory markers. Compared with patients in the high LCR group, those in the low LCR group had worse survival (hazard ratio (HR) 1.64, 95% confidence interval (95%CI) 1.42-1.91, p < 0.001). Compared with patients in the low CAR group, those in the high CAR group had worse survival (HR 1.65, 95% CI 1.43-1.91, p < 0.001). Older adults with cancer with an ECOG PS score of 2 or 3-4 and a high inflammation (low LCR, 13.3 months and 9.2 months, respectively; or high CAR, 9.6 months and 9.6 months, respectively) had shorter median survival time compared to those with an ECOG PS score of 0/1 and a low inflammation (high LCR, 77.4 months; or low CAR, 77.0 months). CONCLUSION: LCR and CAR might be the better predictive immune inflammatory factors for OS, which improved the survival prediction of different ECOG PS groups in older adults with cancer. High ECOG PS (≥2) and high inflammation increased the risk of death in older adults with cancer.

A Novel Inflammation and Insulin Resistance Related Indicator to Predict the Survival of Patients With Cancer.

Background: Systemic inflammation and insulin resistance (IR) are closely related in patients with cancer. However, there is no relevant indicator that combines inflammation and IR to predict patient prognosis. Therefore, this study aimed to develop and validate a novel inflammation- and IR-related marker in patients with cancer. Methods: The total cohort of this study included 5221 patients with cancer, and the training and validation cohorts were randomized in a 7:3 ratio. C-reactive protein (CRP) and fasting triglyceride glucose (TyG) were used to reflect patients' inflammation and IR status, respectively. The CRP-TyG index (CTI) was composed of CRP and TyG. The concordance (C)-index, receiver operator characteristic (ROC) curve, and calibration curve reflected the prognostic predictive power of CTI. Univariate and multivariate survival analyses predicted the prognostic value of CTI in patients with cancer. Results: The C-indices of CTI in patients with cancer were 0.636, 0.617, and 0.631 in the total, training, and validation cohorts, respectively. The 1-, 3-, and 5-year ROC and calibration curves showed that CTI had a good predictive ability of survival in patients with cancer. Meanwhile, patients with high CTI had a worse prognosis compared to patients with low CTI (total cohort: hazard ratio [HR] = 1.46, 95% confidence interval [95% CI] = 1.33-1.59; training cohort: HR = 1.36, 95% CI = 1.22-1.52; validation cohort: HR = 1.73, 95% CI = 1.47-2.04]. Conclusion: The CTI is a useful prognostic indicator of poor prognosis and a promising tool for treatment strategy decision-making in patients with cancer.

Prognostic importance of systemic inflammation and insulin resistance in patients with cancer: a prospective multicenter study.

BACKGROUND: Systemic inflammation and insulin resistance (IR) are often associated with poor prognosis in cancer. This study aimed to investigate the prognostic value of surrogate systemic inflammation and IR indices in patients with cancer. METHODS: This multicenter prospective study included 5,221 patients with cancer, with a mean age of 59.41±11.15 years, of whom 3,061 (58.6%) were male. The surrogate IR indices included low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LHR) ratio, total cholesterol to high-density lipoprotein cholesterol (TC/ HDL-c) ratio, triglyceride to high-density lipoprotein cholesterol (TG/HDL-c) ratio, and fasting triglyceride glucose (TyG). Prognostic receiver operator characteristic (ROC) curves and C-indices were used to select a better surrogate IR index in patients with cancer. The prognostic value of the indicators was evaluated using univariate and multivariate survival analyses. RESULTS: In this study, the median survival time of patients was 44.5 (40.5-51.4) months, and the overall mortality in the 12-month period was 1,115 (53.7%), with 196 mortality events per 1,000 patient-years of patients' follow-up. The prognostic ROC curve and C-index suggested that the prognostic value of LHR was better than that of the other IR indices. The multivariate-adjusted hazard ratios (HRs) for overall survival (OS) were higher in patients with high C-reactive protein (CRP) (HR, 1.51; 95% confidence interval [CI]: 1.38-1.65) and high LHR (HR, 1.20; 95% CI: 1.06-1.37), respectively. The mortality rate of patients with both high CRP and LHR was 1.75-fold higher than that of patients with both low CRP and LHR. CONCLUSION: Both CRP and LHR showed good survival predictions in patients with cancer. CRP combined with LHR can improve the predictive power of patients with cancer.

Association of Systemic Inflammation and Overall Survival in Elderly Patients with Cancer Cachexia - Results from a Multicenter Study.

BACKGROUND: Systemic inflammation and cachexia are associated with adverse clinical outcomes in elderly patients with cancer. The survival outcomes of elderly patients with cancer cachexia (EPCC) with high inflammation and a high risk of mortality are unknown. This study aimed to investigate the impact of high inflammation on the prognosis of EPCC patients with high mortality. PATIENTS AND METHODS: This multicenter cohort study included 746 EPCC (age >65 years) with a mean age of 72.00 ± 5.24 years, of whom 489 (65.5%) were male. The cut-off value for the inflammation index was obtained using the optimal survival curve. The different inflammatory indicators were assessed using the concordance index (C-index), decision curve analysis (DCA), and prognostic receiver operating characteristic (ROC). The high mortality risk group of EPCC was defined by the 2011 Fearon Cancer Diagnostic Consensus. EPCC were divided into the high-risk group, which satisfies three diagnostic criteria, and a low-risk group, which satisfies only one or two diagnostic criteria. RESULTS: The C-index, DCA, and prognostic ROC indicated the superiority of advanced lung cancer inflammation index (ALI) compared with other indicators, including neutrophil-lymphocyte ratio (NLR), prognostic nutritional index (PNI), systemic immune-inflammation index (SII), and platelet-lymphocyte ratio (PLR). Whether ALI was used as a continuous or a categorical variable, ALI had a better prognostic value in EPCC compared with other inflammatory indicators. In particular, patients with low ALI (<25.03) had a worse overall survival (OS) than patients with high ALI (≥25.03) (P < 0.001, HR [95% CI] = 2.092 [1.590-2.751]). The combination effect analysis showed that the risk of mortality of the patients in the low-ALI and high-risk groups was 3.095-fold higher than that of patients in the high-ALI and low-risk groups. CONCLUSION: The prognostic and discriminative value of the inflammatory indicator ALI was better than that of NLR, PNI, SII, and PLR in EPCC. The high-risk group of EPCC with a low ALI would increase the death risk of OS.

Geriatric Nutrition Risk Index: Prognostic factor related to inflammation in elderly patients with cancer cachexia.

BACKGROUND: Systemic inflammation and cachexia are associated with adverse clinical outcomes in elderly patients with cancer. The Geriatric Nutritional Risk Index (GNRI) is a simple and useful tool to assess these conditions, but its predictive ability for elderly patients with cancer cachexia (EPCC) is unknown. METHODS: This multicentre cohort study included 746 EPCC with an average age of 72.00 ± 5.24 years, of whom 489 (65.5%) were male. The patients were divided into two groups (high GNRI group ≥91.959 vs. low GNRI group <91.959) according to the optimal cut-off value of the ROC curve. The calibration curves were performed to analyse the prognostic, predictive ability of GNRI. Comprehensive survival analyses were utilized to explore the relationship between GNRI and the overall survival (OS) of EPCC. Interaction analysis was used to investigate the comprehensive effects of low GNRI and subgroup parameters on the OS of EPCC. RESULTS: In this study, a total of 2560 patients were diagnosed with cancer cachexia, including 746 cases of EPCC. During the 3.6 year median follow-up, we observed 403 deaths. The overall mortality rate for EPCC at 12 months was 34.3% (95% CI: 62.3% to 69.2%), and resulting in rate of 278 events per 1000 patient-years. The GNRI score of EPCC was significantly lower than those of young patients with cancer cachexia (P < 0.001). The 1, 3, and 5 year calibration curves showed that the GNRI score had good survival prediction in the OS of EPCC. The GNRI could predict the OS of EPCC, whether as a continuous variable or a categorical variable. Particularly, we also found that low GNRI score (<91.959) of EPCC had a worse prognosis than those with a high GNRI score (≥91.959, P = 0.001, HR = 1.728, 95% CI: 1.244-2.401). Consistent results were observed in the tumour subgroups of gastric cancer and colorectal cancer. Notably, similar results were observed in the sensitivity analysis. In the subgroup analysis, the low GNRI has a combined effect with age (<70 years) on poor OS of EPCC. The results of the prognostic risk model found that the lower the GNRI score, the greater the prognostic risk score, and the greater the risk of death in EPCC. CONCLUSIONS: For the first time, this study found that the GNRI score can serve as an independent prognostic factor for the OS of EPCC.

Lycoris wulingensis, a dwarf new species of Amaryllidaceae from Hunan, China.

Lycoris wulingensis S.Y. Zhang, a new species from Hunan Province (central South China), is described and illustrated. This new species is a fertile diploid plant and its karyotype is 2n = 22. It is most similar to L. × haywardii in morphology, but the latter is a hybrid species and distributed in East China and the plant is much larger. Amongst the original species, L. wulingensis is similar to L. radiata, but differs from it in its flowers being rose-red (vs. red) and stamens and tepals are nearly the same length (vs. stamens significantly longer than tepals).

Association Between Systemic Inflammation and Malnutrition With Survival in Patients With Cancer Sarcopenia-A Prospective Multicenter Study.

OBJECTIVE: Systemic inflammation and malnutrition are correlated with cancer sarcopenia and have deleterious effects on oncological outcomes. However, the combined effect of inflammation and malnutrition in patients with cancer sarcopenia remains unclear. METHODS: We prospectively collected information on 1,204 patients diagnosed with cancer sarcopenia. the mean (SD) age was 64.5 (11.4%) years, and 705 (58.60%) of the patients were male. The patients were categorized into the high advanced lung cancer inflammation index (ALI) group (≥18.39) and the low ALI group (<18.39) according to the optimal survival cut-off curve. We selected the optimal inflammation marker using the C-index, decision curve analysis (DCA), and a prognostic receiver operating characteristic curve. Univariate and multivariate survival analyses were performed to determine the prognostic value of the optimal inflammation indicator. We also analyzed the association between inflammation and malnutrition in patients with cancer. RESULTS: The C-index, DCA, and prognostic area under the curve of ALI in patients with cancer sarcopenia were higher or better than those of neutrophil-lymphocyte ratio (NLR), prognostic nutritional index (PNI), systemic immune-inflammation index (SII), and platelet-lymphocyte ratio (PLR). The prognosis for patients in the low ALI group was worse than that of patients in the high ALI group [HR (95%CI) = 1.584 (1.280-1.959), P < 0.001]. When the ALI was divided into quartiles, we observed that decreased ALI scores strongly correlated with decreased overall survival (OS). Patients with both a low ALI and severe malnutrition (vs. patients with high ALI and well-nourished) had a 2.262-fold death risk (P < 0.001). Subgroup analysis showed a significant interactive association between the ALI and death risk in terms of TNM stage (P for interaction = 0.030). CONCLUSIONS: The inflammation indicator of the ALI was better than those of the NLR, PNI, SII, and PLR in patients with cancer sarcopenia. Inflammation combined with severe malnutrition has a nearly 3-fold death risk in patients with cancer sarcopenia, suggesting that reducing systemic inflammation, strengthening nutritional intervention, and improving skeletal muscle mass are necessary.

DeepMRMP: A new predictor for multiple types of RNA modification sites using deep learning.

RNA modification plays an indispensable role in the regulation of organisms. RNA modification site prediction offers an insight into diverse cellular processing. Regarding different types of RNA modification site prediction, it is difficult to tell the most relevant feature combinations from a variant of RNA properties. Thereby, the performance of traditional machine learning based predictors relied on the skill of feature engineering. As a data-driven approach, deep learning can detect optimal feature patterns to represent input data. In this study, we developed a predictor for multiple types of RNA modifications method called DeepMRMP (Multiple Types RNA Modification Sites Predictor), which is based on the bidirectional Gated Recurrent Unit (BGRU) and transfer learning. DeepMRMP makes full use of multiple RNA site modification data and correlation among them to build predictor for different types of RNA modification sites. Through 10-fold cross-validation of the RNA sequences of H. sapiens, M. musculus and S. cerevisiae, DeepMRMP acted as a reliable computational tool for identifying N1-methyladenosine (m1A), pseudouridine (Ψ), 5-methylcytosine (m5C) modification sites.

Indole Alkaloids Inhibiting Neural Stem Cell from Uncaria rhynchophylla.

Uncaria rhynchophylla is commonly recognized as a traditional treatment for dizziness, cerebrovascular diseases, and nervous disorders in China. Previously, the neuro-protective activities of the alkaloids from U. rhynchophylla were intensively reported. In current work, three new indole alkaloids (1-3), identified as geissoschizic acid (1), geissoschizic acid N 4-oxide (2), and 3ß-sitsirikine N 4-oxide (3), as well as 26 known analogues were isolated from U. rhynchophylla. However, in the neural stem cells (NSCs) proliferation assay for all isolated compounds, geissoschizic acid (1), geissoschizic acid N 4-oxide (2), isocorynoxeine (6), isorhynchophylline (7), (4S)-akuammigine N-oxide (8), and (4S)-rhynchophylline N-oxide (10) showed unexpected inhibitory activities at 10 µM. Unlike previous neuro-protective reports, as a warning or caution, our finding showcased a clue for possible NSCs toxicity and the neural lesions risk of U. rhynchophylla, while the structure-activity relationships of the isolated compounds were discussed also.

Prognostic significance of osteopontin in acute myeloid leukemia: A meta-analysis.

Osteopontin (OPN) has been investigated in the field of tumor research for several years. However, the prognostic role of OPN overexpression in acute myeloid leukemia (AML) remains controversial. A meta-analysis of four studies, including a total of 492 patients, was performed to determine the association of OPN with overall survival (OS) in AML patients. The random-effects model of Der Simonian and Laird was used to synthesize data; hazard ratio (HR) with its 95% confidence interval (CI) was used as the effect size estimate. It was observed that serum-based OPN was inversely correlated with OS and the difference was statistically significant (HR=1.83; 95% CI: 1.43-2.35; P<0.001). Experimental findings indicate that OPN overexpression is associated with a poor prognosis in AML and may be of prognostic value for AML stage and metastasis.

JAK2 inhibitor TG101348 overcomes erlotinib-resistance in non-small cell lung carcinoma cells with mutated EGF receptor.

Non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations are responsive to EGFR-tyrosine kinase inhibitor (EGFR-TKI). However, NSCLC patients with secondary somatic EGFR mutations are resistant to EGFR-TKI treatment. In this study, we investigated the effect of TG101348 (a JAK2 inhibitor) on the tumor growth of erlotinib-resistant NSCLC cells. Cell proliferation, apoptosis, gene expression and tumor growth were evaluated by diphenyltetrazolium bromide (MTT) assay, flow cytometry, terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining, Western Blot and a xenograft mouse model, respectively. Results showed that erlotinib had a stronger impact on the induction of apoptosis in erlotinib-sensitive PC-9 cells but had a weaker effect on erlotinib-resistant H1975 and H1650 cells than TG101348. TG101348 significantly enhanced the cytotoxicity of erlotinib to erlotinib-resistant NSCLC cells, stimulated erlotinib-induced apoptosis and downregulated the expressions of EGFR, p-EGFR, p-STAT3, Bcl-xL and survivin in erlotinib-resistant NSCLC cells. Moreover, the combined treatment of TG101348 and erlotinib induced apoptosis, inhibited the activation of p-EGFR and p-STAT3, and inhibited tumor growth of erlotinib-resistant NSCLC cells in vivo. Our results indicate that TG101348 is a potential adjuvant for NSCLC patients during erlotinib treatment.

Infections during induction therapy of protocol CCLG-2008 in childhood acute lymphoblastic leukemia: a single-center experience with 256 cases in China.

BACKGROUND: Infections remain a major cause of therapy-associated morbidity and mortality in children with acute lymphoblastic leukemia (ALL). METHODS: We retrospectively analyzed the medical charts of 256 children treated for ALL under the CCLG-2008 protocol in Beijing Children's Hospital. RESULTS: There were 65 infectious complications in 50 patients during vincristine, daunorubicin, L-asparaginase and dexamethasone induction therapy, including microbiologically documented infections (n = 12; 18.5%), clinically documented infections (n = 23; 35.3%) and fever of unknown origin (n = 30; 46.2%). Neutropenia was present in 83.1% of the infectious episodes. In all, most infections occurred around the 15 th day of induction treatment (n = 28), and no patients died of infection-associated complications. CONCLUSIONS: The infections in this study was independent of treatment response, minimal residual diseases at the end of induction therapy, gender, immunophenotype, infection at first visit, risk stratification at diagnosis, unfavorable karyotypes at diagnosis and morphologic type. The infection rate of CCLG-2008 induction therapy is low, and the outcome of patients is favorable.

Experimental study on inhibition effects of the XAF1 gene against lung cancer cell proliferation.

OBJECTIVE: To investigate the effect of high expression of XAF1 in vivo or in vitro on lung cancer cell growth and apoptosis. METHODS: 1. The A549 human lung cancer cell line was transfected with Ad5/F35 - XAF1, or Ad5/ F35 - Null at the same multiplicity of infection (MOI); (hereinafter referred to as transient transfected cell strain); XAF1 gene mRNA and protein expression was detected by reverse transcription polymerase chain reaction (RT- PCR) and Western blotting respectively. 2. Methyl thiazolyl tetrazolium (MTT) and annexin V-FITC/PI double staining were used to detect cell proliferation and apoptosis before and after infection of Ad5/F35 - XAF1 with Western blotting for apoptosis related proteins, caspase 3, caspase - 8 and PARP. 3. After the XAF1 gene was transfected into lung cancer A549 cells by lentiviral vectors, and selected by screening with Blasticidin, reverse transcription polymerase chain reaction (RT-PCR) and Western blotting were applied to detect mRNA and protein expression, to establish a line with a stable high expression of XAF1 (hereinafter referred to as stable expression cell strain). Twenty nude mice were randomly divided into groups A and B, 10 in each group: A549/ XAF1 stable expression cell strain was subcutaneously injected in group A, and A549/Ctrl stable cell line stable expression cell strain in group B (control group), to observe transplanted tumor growth in nude mice. RESULTS: The mRNA and protein expression of XAF1 in A549 cells transfected by Ad5/F35 - XAF1 was significantly higher than in the control group. XAF1 mediated by adenovirus vector demonstrated a dose dependent inhibition of lung cancer cell proliferation and induction of apoptosis. This was accompanied by cleavage of caspase -3, -8, -9 and PARP, suggesting activation of intrinsic or extrinsic apoptotic pathways. A cell strain of lung cancer highly expressing XAF1 was established, and this demonstrated delayed tumor growth after transplantation in vivo. CONCLUSION: Adenovirus mediated XAF1 gene expression could inhibit proliferation and induce apoptosis in lung cancer cells in vitro; highly stable expression of XAF1 could also significantly inhibit the growth of transplanted tumors in nude mouse, with no obvious adverse reactions observed. Therefore, the XAF1 gene could become a new target for lung cancer treatment.

Meta-analysis of randomized trials comparing the effectiveness of on-pump and off-pump coronary artery bypass.

BACKGROUND: The growing enthusiasm for coronary artery bypass grafting (CABG) without cardiopulmonary bypass (CPB) is emerging, but the role of off-pump coronary artery bypass (OPCAB) in clinical practice remains controversial. The purpose of this study was to assess differences in the incidences of stroke, atrial fibrillation (AF), and myocardial infarction (MI) between OPCAB and conventional coronary artery bypass grafting (CCABG) by meta-analyses of randomized clinical trials. METHODS: A literature search for the period before March 2010 supplemented with manual bibliographic review was performed for all Chinese or English publications in Medline, the Science Citation Index Expanded, the Cochrane Central Register of Controlled Trials (CENTRAL) and CBMdisc. A systematic overview (meta-analyses) of randomized clinical trials was conducted to evaluate the differences between OPCAB and CCABG in the incidences of stroke, AF, and MI. The meta-analysis was performed using RevMan 5 software. RESULTS: Forty-three randomized clinical trials were selected for meta-analysis after screening a total of 356 references, with 8104 patients in the OPCAB group and 8724 cases in the CCABG group. The meta-analyses of these trials showed no significant difference between OPCAB and CCABG in the incidences of stroke (odds ratio (OR) = 0.80, 95% confidence interval (CI) = 0.52 - 1.22, P = 0.30) and MI (OR = 0.73, 95%CI = 0.52 - 1.02, P = 0.06). However, we found a significantly reduced risk of AF (OR = 0.65, 95%CI = 0.52 - 0.82, P = 0.0002) in off-pump patients. CONCLUSIONS: Our meta-analyses suggest that OPCAB reduces the risk of postoperative AF compared with CCABG, but there is no significant difference in the incidences of stroke and MI between OPCAB and CCABG.

[Judging the postoperative lymph node metastasis of esophagus cancer patients with pN0 stage by detecting MTA1 protein expression].

OBJECTIVE: To investigate the feasibility for judging the postoperative lymph node metastasis of esophagus cancer patients with pN0 stage by detecting the protein expression of metastasis-associated protein 1 (MTA1). METHODS: Immunohistochemistry was used to detect the expression of MTA1 protein in lymph node of esophageal squamous cell carcinoma (ESCC) with pN0 stage. RESULTS: (1) There were no significant differences in age, gender and differentiation among the lymph node metastasis (P > 0.05), but not with pT stage (P < 0.05; χ(2) = 13.29). (2) There were no significant differences among the expression of MTA1 protein and age, gender and differentiation (P > 0.05), but not with differentiation and pT stage (P < 0.05; χ(2) = 18.61). Both stages pT1b and pT3 had higher expression of MTA1 protein than stage pT1a (P < 0.05; χ(2) = 25.54). (3) The curve of lymph node metastasis showed that the patients with no/lower MTA1 protein expression had a lower metastasis rate than those a higher MTA1 protein expression (P < 0.05; χ(2) = 16.63). (4) The results of multivariate analysis confirmed that T status and MTA1 protein over-expression were independent risk factors for pN0 stage ESCC. CONCLUSION: Detecting MTA1 protein expression is helpful for judging the lymph node metastasis of ESCC patients with pN0 stage. And its over-expression may used as a guide in the decision-making of postoperative adjuvant therapy.

Recombinant adenovirus with human indoleamine-2,3-dioxygenase and hepatitis B virus preS was constructed and expressed in HepG2 cells.

BACKGROUND: Indoleamine-2,3-dioxygenase (IDO) is proven to suppress hepatitis B virus (HBV) specific immune response and depletion of IDO may be a useful approach for HBV therapy. To test this concept, we constructed recombinant adenovirus with human IDO and HBV preS, which would form the basis for future in vivo experiments. METHODS: The fragment of human IDO and HBV preS cDNA were subcloned into multiple cloning sites in an adenoviral vector system containing two cytomegalovirus (CMV) promoters. Recombination was conducted in the Escherichia coli BJ5183. The recombinant adenovirus containing hIDO gene and HBVpreS gene was packaged and amplified in 293 cells. Integration was confirmed by polymerase chain reaction as well as the quantification of viral titers. HepG2 cells were infected with the recombinant adenovirus and mRNA and protein specific for hIDO and HBVpreS was detected by RT-PCR and Western blotting respectively. RESULTS: The recombinant adenovirus was produced successfully. Its titer was 2.5 × 10(9) efu/ml. IDO and HBVpreS mRNA as well as the encoded proteins could be found in transfected HepG2 cells, but not in control HepG2 cells. CONCLUSION: The transfer of hIDO-HBVpreS with double-promoter adenoviral vector was efficient. The recombinant adenovirus with hIDO and HBV preS would provide the experimental basis for future studies.

XAF1 as a prognostic biomarker and therapeutic target in squamous cell lung cancer.

BACKGROUND: X-linked inhibitor of apoptosis (XIAP)-associated factor 1 (XAF1) is a new tumor suppressor. Low expression of XAF1 is associated with poor prognosis of human cancers. However, the effect of XAF1 on lung cancer remains unknown. In this study, we investigated the expression of XAF1 and its role in squamous cell lung cancer. METHODS: Cancer tissues, cancer adjacent tissues and normal lung tissues were collected from 51 cases of squamous cell lung cancer. The expression of XAF1 mRNA was determined by reverse transcription-polymerase chain reaction (RT-PCR). The expression of XAF1 protein was determined by Western blotting and immunohistochemical staining. Ad5/F35-XAF1 virus was generated. Cell proliferation and apoptosis were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method and flow cytometry (FACS), respectively. RESULTS: The levels of XAF1 protein and mRNA in cancer tissues were significantly lower than those in cancer adjacent and normal lung tissues (P < 0.05). The low expression of XAF1 was associated with tumor grade, disease stage, differentiation status and lymph node metastasis in squamous cell lung cancer patients. The restoration of XAF1 expression mediated by Ad5/F35-XAF1 virus significantly inhibited cell proliferation and induced apoptosis in a dose- and time-dependent manner. CONCLUSION: XAF1 is a valuable prognostic marker in squamous cell lung cancer and may be a potential candidate gene for lung cancer therapy.

Comparison of compensatory sweating and quality of life following thoracic sympathetic block for palmar hyperhidrosis: electrocautery hook versus titanium clip.

BACKGROUND: Video-assisted thoracic sympathetic block is an effective, safe, and minimally invasive method for treatment of primary hyperhidrosis. The purpose of this study was to decide which one of using electrocautery hook and titanium clip is the appropriate procedure for primary palmar hyperhidrosis by assessing the compensatory sweating (CS) and quality of life (QOL) of patients after sympathetic block. METHODS: Between October 2007 to August 2010, 120 patients with primary palmar hyperhidrosis were randomly divided into two groups, electrocautery hook group (60 patients) and titanium clip group (60 patients). All patients were treated by sympathetic block at T4 level. The CS was graded based on severity and location; the QOL was classified to 5 different levels based upon the summed total scores (range from 20 to 100) before and after surgery. The variables were compared. RESULTS: The postoperative follow-up period was 2 months. All patients were cured. Three patients in electrocautery hook group and 1 patient in titanium clip group had a unilateral pneumothorax on chest X-ray, but none of them was necessary to have chest drainage. Neither perioperative mortality nor serious complications such as cardiac arrhythmia or arrest were observed during the operation. No bradycardia or Horner's syndrome occured. CS was not more common in patients in titanium clip group than in those in electrocautery hook group (P = 0.001). Moderate and severe CS was few in all patients, and there was no significant difference between two groups (P = 0.193). Most of the patients feel a notable improvement of the the QOL; nevertheless, there was no significant difference between the groups (P = 0.588). CONCLUSIONS: Both electrocautery hook and titanium clip used for sympathetic block at the T4 level are effective, safe, and minimally invasive for palmar hyperhidrosis. Because of the lower severity of CS and the similar improvements in the QOL after operation, we prefer to use of titanium clip for treating palmar hyperhidrosis.

Role of hepatic arterial ischaemia in biliary fibrosis following liver transplantation.

BACKGROUND: In clinical liver transplantation, whether the delay of hepatic arterial ischaemia increases biliary fibrosis or not is controversial. We designed a liver transplantation model to test this controversy and explore its mechanism. METHODS: Twelve dogs were divided into two groups randomly: hepatic arterial ischaemia (HAI) and control groups. In HAI group, hepatic artery was perfused 60 minutes after portal perfusion, but in control group, hepatic arterial perfusion was simultaneous with portal perfusion. The pathological changes of intrahepatic bile ducts were observed. Transforming growth factor beta 1 (TGF-beta1), expressed in epithelial cells of intrahepatic bile duct, was detected by immunohistochemical streptoadividin-biotin complex method. Expressions of Smad3, P-Smad3 and the transcriptional levels of alpha smooth muscle actin (alpha-SMA) mRNA in intrahepatic bile ducts were detected by Western blotting and RT-PCR respectively. RESULTS: Compared with the control group, more collagen deposition and leucocytic infiltration could be seen in biliary vessel walls. Significantly more buffy particles, which are the proteins of TGF-beta1, could be seen in biliary epithelial cells. P-Smad3 and alpha-SMA mRNA (as ratio to corresponding beta-actin) in intrahepatic bile ducts were 1.82 +/- 0.18 and 1.86 +/- 0.73 respectively in HAI group, significantly higher than those in control group (0.59 +/- 0.09 and 0.46 +/- 0.18, respectively). CONCLUSIONS: Hepatic arterial ischaemia could increase the deposition of collagen fibres, trigger the transdifferentiation of myofibroblasts in intrahepatic bile duct and might result in biliary fibrosis by activating the TGF-beta1 signalling pathway.

Uniportal versus biportal video-assisted thoracoscopic sympathectomy for palmar hyperhidrosis.

BACKGROUND: Video-assisted thoracoscopic sympathectomy had replaced open surgery. The aim of this study was to compare the outcomes of using a single port and two ports to perform video-assisted thoracoscopic sympathectomy for palmar hyperhidrosis. METHODS: Between April 2006 and February 2008, 20 cases underwent video-assisted thoracoscopic sympathectomy through one port (uniportal group) and 25 cases through two ports (biportal group). The variables including the operating time, hospital stay, pain scores, postoperative complications, incidence of symptom recurrence and patient satisfaction were compared. The mean postoperative follow-up period was 11.5 months (range, 3 - 25 months). RESULTS: The hands of all patients were warm and dry after operation. No conversion to open surgery was necessary, and no operative mortality was recorded in either group. The mean inpatient pain scores were significantly higher in the biportal group (1.2 +/- 0.6) than that in the uniportal group (0.8 +/- 0.5, P = 0.025). For the first three weeks after operation, four out of 20 (20%) patients in the uniportal group constantly suffered from mild or moderate residual pain while eight out of 25 (32%) cases in the biportal group (P = 0.366). Among them, two cases in the uniportal group and five cases in the biportal group need to take analgesics. Our mean operative time (bilateral sympathectomy) in the uniportal group ((39.5 +/- 10.0) minutes) was shorter than that in biportal group ((49.7 +/- 10.6) minutes, P = 0.02). There were no significant differences between two groups in terms of the mean hospital stay, compensatory sweating, and patient satisfaction. Two patients in the biportal group and three in the uniportal group experienced a unilateral pneumothorax. None of them required chest drainage. No patient experienced Horner's syndrome, and no recurrent symptoms were observed in either groups. CONCLUSIONS: Both uniportal and biportal video-assisted thoracoscopic sympathectomy are effective, safe, and minimally invasive for palmar hyperhidrosis. Comparing with the biportal approach, the uniportal approach causes less postoperative pain and less operative time, and is a more reasonable procedure in treatment of palmar hyperhidrosis.