Repeat hepatic resection versus radiofrequency ablation for recurrent hepatocellular carcinoma: retrospective multicentre study.

BACKGROUND: The therapeutic value of repeat hepatic resection (rHR) or radiofrequency ablation (RFA) for recurrent hepatocellular carcinoma (HCC) is unknown. This study aimed to investigate the safety and efficacy of rHR or RFA. METHODS: This was a retrospective multicentre study of patients with recurrent HCC within the Milan criteria who underwent rHR or RFA at nine university hospitals in China and Italy between January 2003 and January 2018. Survival after rHR or RFA was examined in unadjusted analyses and after propensity score matching (1 : 1). RESULTS: Of 847 patients included, 307 and 540 underwent rHR and RFA respectively. Median overall survival was 73.5 and 67.0 months after rHR and RFA respectively (hazard ratio 1.01 (95 per cent c.i. 0.81 to 1.26)). Median recurrence-free survival was longer after rHR versus RFA (23.6 versus 15.2 months; hazard ratio 0.76 (95 per cent c.i. 0.65 to 0.89)). These results were confirmed after propensity score matching. RFA was associated with lower morbidity of grade 3 and above (0.6 versus 6.2 per cent; P < 0.001) and shorter hospital stay (8.0 versus 3.0 days, P < 0.001) than rHR. CONCLUSION: rHR was associated with longer recurrence-free survival but not overall survival compared with RFA.

No high Tibetan Plateau until the Neogene.

The Late Paleogene surface height and paleoenvironment for the core area of the Qinghai-Tibetan Plateau (QTP) remain critically unresolved. Here, we report the discovery of the youngest well-preserved fossil palm leaves from Tibet. They were recovered from the Late Paleogene (Chattian), ca. 25.5 ± 0.5 million years, paleolake sediments within the Lunpola Basin (32.033°N, 89.767°E), central QTP at a present elevation of 4655 m. The anatomy of palms renders them intrinsically susceptible to freezing, imposing upper bounds on their latitudinal and altitudinal distribution. Combined with model-determined paleoterrestrial lapse rates, this shows that a high plateau cannot have existed in the core of Tibet in the Paleogene. Instead, a deep paleovalley, whose floor was <2.3 km above mean sea level bounded by (>4 km) high mountain systems, formed a topographically highly varied landscape. This finding challenges prevailing views on tectonic processes, monsoon dynamics, and the evolution of Asian biodiversity.

[A study on the effects and safety of sequential humidified high flow nasal cannula oxygenation therapy on the COPD patients after extubation].

Objective: To investigate and compare the effect and safety of nasal high-flow oxygen therapy (HFNCO) and noninvasive ventilation (NIV) therapy after extubation in patients with chronic obstructive pulmonary disease (COPD). Methods: All COPD patients subjected to mechanical ventilation in the Emergency Intensive Unit of the First Affiliated Hospital of Zhejiang University during January 2015 to June 2016 were included in the study. The patients were divided into two groups after extubation and HFNCO and NIV were adopted on each group respectively. Clinical indexes including the patients' general condition, blood gas analysis and pulmonary function before and after extubation, ratio of re-intubation and CT grades were collected and analyzed. Results: There was no significant difference in the incidence of aspiration (4.8% vs 8.3%), pressure sores (0 vs 8.3%) and delirium (4.8% vs 12.5%) between the two groups (all P>0.05). At 12 h after extubation, the oxygenation index of NIV group was significantly higher than that of the HFNCO group (265±29 vs 297±33; P<0.05), while no significant difference in PCO(2) (P>0.05). For 24 h and 72 h after extubation, there was no statistically significant difference in oxygenation index and PCO(2) between the both groups (P>0.05). The intensive care unit (ICU) retention time in HFNCO group was significantly lower than that in NIV group (13.7±0.8 vs 15.2±0.5; P<0.05). In addition, no significant difference between the two groups in mortality and re-intubation rate at 28 d (P>0.05) was observed. Conclusion: HFNCO is effective and safe in the treatment of COPD patients after extubation, and it is hence valuable for further clinical application.

[Comparison of the prognosis after hepatic resection for patients with Barcelona Clinical Liver Cancer Stage B hepatocellular carcinoma].

Objective: To compare the efficacy of hepatic resection (HR) in patients with Barcelona Clinical Liver Cancer (BCLC) Stage B hepatocellular carcinoma (HCC) and examine how that efficacy has changed over time in a large medical center. Methods: A consecutive sample of 918 patients with preserved liver function and large and/or multinodular HCC who were treated by initial HR were divided into three groups: those with a single tumor ≥5 cm in diameter (n=582), 2-3 tumors with a maximum diameter>3 cm (n=223), or>3 tumors of any diameter (n=113). Hospital mortality and overall survival (OS) in each group were compared for the years 2001-2007 and 2008-2013. Results: Patients with >3 tumors showed the highest incidence of hospital mortality of all groups (P<0.05). Kaplan-Meier survival analysis showed that OS varied across the three groups as follows: single tumor>2-3 tumors >3+ tumors (all P<0.05). OS rate at 5 years ranged from 24% to 41% in all three groups for the period 2001-2007, and from 35% to 46% for the period 2008-2013. OS was significantly higher during the more recent 6-year period in the entire patient population, those with single tumor, and those with 3+ tumors (all P<0.05). However, in patients with 2-3 tumors, OS was only slightly higher during the more recent 6-year period (P=0.084). Conclusions: Prognosis of three types of HCC was different. Patients with >3 tumors show the highest hospital mortality and lowest OS after HR. OS has been improving for all three types of HCC at our medical center as a consequence of improvements in surgical technique and perioperative management.

High-Brightness High-Energy Electron Beams from a Laser Wakefield Accelerator via Energy Chirp Control.

By designing a structured gas density profile between the dual-stage gas jets to manipulate electron seeding and energy chirp reversal for compressing the energy spread, we have experimentally produced high-brightness high-energy electron beams from a cascaded laser wakefield accelerator with peak energies in the range of 200-600 MeV, 0.4%-1.2% rms energy spread, 10-80 pC charge, and ∼0.2 mrad rms divergence. The maximum six-dimensional brightness B_{6D,n} is estimated as ∼6.5×10^{15} A/m^{2}/0.1%, which is very close to the typical brightness of e beams from state-of-the-art linac drivers. These high-brightness high-energy e beams may lead to the realization of compact monoenergetic gamma-ray and intense coherent x-ray radiation sources.

Recurrence after anatomic resection versus nonanatomic resection for hepatocellular carcinoma: a meta-analysis.

The impact of anatomic resection (AR) as compared to non-anatomic resection (NAR) for hepatocellular carcinoma (HCC) as a factor for preventing intra-hepatic and local recurrence after the initial surgical procedure remains controversial. A systematic review and meta-analysis of nonrandomized trials comparing anatomic resection with non-anatomic resection for HCC published from 1990 to 2010 in PubMed and Medline, Cochrane Library, Embase, and Science Citation Index were therefore performed. Intra-hepatic recurrence, including early and late, and local recurrence were considered as primary outcomes. As secondary outcomes, 5 year survival and 5 year disease-free survival were considered. Pooled effects were calculated utilizing either fixed effects or random effects models. Eleven non-randomized studies including 1,576 patients were identified and analyzed, with 810 patients in the AR group and 766 in the NAR group. Patients in the AR group were characterized by lower prevalence of cirrhosis, more favorable hepatic function, and larger tumor size and higher prevalence of macrovascular invasion compared with patients in the NAR group. Anatomic resection significantly reduced the risks of local recurrence and achieved a better 5 years disease-free survival. Also, anatomic resection was marginally effective for decreasing the early intra-hepatic recurrence. However, it was not advantageous in preventing late intra-hepatic recurrence compared with non-anatomic resection. No differences were found between AR and NAR with respect to postoperative morbidity, mortality, and hospitalization. Anatomic resection can be recommended as superior to non-anatomic resection in terms of reducing the risks of local recurrence, early intra-hepatic recurrence and achieving a better 5 year disease-free survival in HCC patients.

Association of chemokine CXCL12-3'G801A polymorphism with systemic lupus erythematosus in a Han Chinese population.

CXCL12, also known as stromal cell-derived factor (SDF-1), is a CXC chemokine. Recent reports have shown that CXCL12 might play key roles in a murine model of lupus and in patients with systemic lupus erythematosus (SLE). A common variant at position 801 in 3'-untranslated region in CXCL12 gene (designated CXCL12-3'G801A) has been reported in association with autoimmune diseases, such as type 1 diabetes and systemic sclerosis. We investigated the influence of CXCL12-3'G801A polymorphism on susceptibility to SLE by genotyping this single nucleotide polymorphism in 422 SLE patients and 374 healthy controls. The frequency of G/G homozygote was observed in 60.0% of SLE patients and in 52.7% of healthy individuals (χ(2 )= 4.275, p = 0.039). Compared with patients with G/A and A/A genotype, SLE patients with G/G genotype were also more prone to developing photosensitivity (χ(2 )= 6.778, p = 0.034), renal damage (χ(2 )= 6.388, p = 0.041) and to producing antibodies against nucleosomes (χ(2 )= 8.341, p = 0.015). Moreover, the plasma level of CXCL12α was also significantly increased in patients with G/G homozygote than in healthy controls carrying the same genotype [(4067.0 ± 1092.3) pg/ml vs. (3278.5 ± 547.4) pg/ml, p = 0.002]. Our results suggest that polymorphism in CXCL12-3'G801A might be a genetic risk factor for developing SLE. The association of G/G homozygote with nephritis and skin damage developed in SLE patients might be due to its effects upon the production of auto-antibodies and CXCL12 protein.

Vitamin D receptor gene BsmI polymorphism B allele, but not BB genotype, is associated with systemic lupus erythematosus in a Han Chinese population.

The vitamin D receptor (VDR) gene is a candidate gene for susceptibility to autoimmune disorders. Association studies of VDR polymorphisms and risk of systemic lupus erythematosus (SLE) have often produced conflicting results in different ethnic backgrounds. The aim of this study is to test the association between VDR gene BsmI polymorphism and the genetic susceptibility to SLE in a Han Chinese population. Three hundred and thirty-seven patients with SLE and 239 healthy controls were genotyped for the VDR gene BsmI polymorphism (rs1544410) by polymerase chain reaction and restriction fragment length polymorphism analysis in this study, after which the relationship between BsmI polymorphisms and the mRNA expression of VDR, as well as clinical manifestations in patients with SLE, was evaluated. It was found that the frequency of B allele was significantly increased in SLE relative to the control group (χ(2) = 4.681, p = 0.031), although the distribution of VDR BsmI polymorphism genotype frequencies did not differ significantly between patients and controls (χ(2) = 4.098, p = 0.129). Moreover, VDR B allele was found to be associated with lupus nephritis (p = 0.027) and also with production of anti-nucleosome antibodies (p = 0.037). The mRNA of VDR was markedly down-regulated in patients with VDR B allele compared with that in patients without B allele (p = 0.016). Our results indicate a possible role of genetic factors (the VDR B allele) in influencing disease susceptibility in Han Chinese patients. Also, VDR B allele is associated with the development of nephritis and the down-regulation of VDR mRNA expression in SLE.

Adoptive immunotherapy for postoperative hepatocellular carcinoma: a systematic review.

The high risk of recurrence in post-operative hepatocellular carcinoma (HCC) highlights the need for an effective adjuvant treatment. A systematic review of randomised controlled trials (RCTs) was performed to evaluate the clinical efficacy of adjuvant adoptive immunotherapy (AIT) for post-operative HCC patients. Electronic (MEDLINE, EMBASE and Cochrane Library databases) and manual searches were conducted throughout May 2011 to identify RCTs evaluating postoperative AIT for patients with HCC. Methodological quality was assessed in accordance with the QUOROM statement. Four RCTs totalling 423 patients met the eligibility criteria. All RCTs reported significantly improved disease-free survival rate or reduced recurrence rate after treating with adjuvant AIT (p < 0.05). The overall survival rates of AIT group are slightly higher than those of the control group in one study. Moreover, AIT was a safe treatment, with fever as the main adverse effects. This study adds to the evidence that postoperative HCC patients treated with adjuvant AIT show an improvement in disease-free survival rate or recurrence rate.

Scientific publications in international anaesthesiology journals: a 10-year survey.

Significant growth has been seen in the field of anaesthesiology in recent decades. The current geographic distribution of the publications on anaesthesia research may be different from ten years ago. We performed this literature survey to examine the national origin of articles published in international anaesthesiology journals and to evaluate their contribution to anaesthesia research. Articles published in 18 major anaesthesiology journals from 2000 to 2009 were identified from the PubMed database and the Science Citation Index. A total of 30,191 articles were published in the selected 18 journals from 2000 to 2009. The country responsible for the largest number of articles was the United States of America (29.4%), followed by the United Kingdom, Germany, Japan, Canada, Australia and France. Denmark, Switzerland and Finland had the largest number of articles per capita. Anesthesia & Analgesia published the most number of articles from 2000 to 2009, followed by Anesthesiology, Pain and the British Journal of Anaesthesia. The numbers of clinical studies and randomised controlled trials decreased markedly from 2000 to 2009.

Volatile anesthetics might be more beneficial than propofol for postoperative liver function in cirrhotic patients receiving hepatectomy.

Hepatic inflow occlusion during the liver surgery may result in a transient ischemia period followed by reperfusion, and may initiate liver injury and lead to postoperative liver dysfunction. Especially in cirrhotic patients, the tolerance time of ischemia is much shorter and the outcome would be worse. Recently, clinical trials had proved that volatile anesthetics rather than propofol can protect myocardial cells from ischemia reperfusion (IR) injury in cardiac surgery. Meanwhile, animal studies had revealed that volatile anesthetics could induce some endogenous protective molecules in the liver such as hypoxia induced factor-1 (HIF-1), heme oxygenase (HO) enzyme system and inducible nitric oxide synthase (iNOS), which make the volatile anesthetics posing the extraordinary anti-oxidative, anti-inflammatory, anti-apoptotic, and vasodilatory characteristics. However, there is still lack of trials to compare the postoperative outcomes such as liver function in cirrhotic patients undergoing liver surgery with inflow occlusion between volatile anesthetics and propofol anesthesia. Hence we hypothesize that with its anti-IR injury characteristics, volatile anesthetics might be the more appropriate choice in cirrhotic patients undergoing liver surgery with occlusion.

Lack of association between HLA-G 14-bp polymorphism and systemic lupus erythematosus in a Han Chinese population.

HLA-G is a non-classical HLA-class Ib molecule with multiple immunoregulatory properties. A 14-bp insertion/deletion polymorphism in the HLA-G gene has been suggested to influence the expression of HLA-G and to associate with certain pathological conditions, including autoimmune diseases. We investigated the influence of the 14-bp insertion/deletion polymorphism in the HLA-G gene on disease susceptibility in systemic lupus erythematosus by genotyping this polymorphism in 231 patients with systemic lupus erythematosus and 367 healthy controls and analyzing the levels of soluble HLA-G in a subset of patients with systemic lupus erythematosus and healthy subjects from a Han Chinese population. No statistically significant differences were observed in the frequencies of the 14-bp insertion/deletion HLA-G alleles or genotypes between controls and patients with systemic lupus erythematosus. However, a significant increased expression of soluble HLA-G was noted in patients with systemic lupus erythematosus (mean value = 230.2 U/ml vs 118.3 U/ml in controls, p = 0.0001). Moreover, patients with high levels of soluble HLA-G presented with higher disease activity and had more neurological involvement. Our results do not support the HLA-G 14-bp insertion/deletion polymorphism as a genetic factor influencing systemic lupus erythematosus susceptibility. It is possible that the expression of soluble HLA-G in systemic lupus erythematosus is enhanced as part of a mechanism to try to restore the tolerance process towards auto-antigens and to counteract inflammation. However, the participation of this molecule in the pathological process of the disease also could not be excluded.

Role of TLR4 for paclitaxel chemotherapy in human epithelial ovarian cancer cells.

BACKGROUND: Paclitaxel has been reported to be a ligand to Toll like receptor 4 (TLR4). Myeloid differentiation factor 88(MyD88) was described as a myeloid differentiation primary response gene. TLR4 signalling owns two pathways: MyD88-dependent and MyD88-independent pathways. XIAP is a key member of the inhibitor of apoptosis protein family. Akt is a major downstream target of growth factor receptor tyrosine kinases, which negatively regulates apoptotic pathways through phosphorylation (pAkt). The aim of the present study is to investigate the role of TLR4 in paclitaxel resistance of ovarian cancer cells. MATERIALS AND METHODS: We reconstructed the RNA interference expression vector, pGenesil-1-U6 specifically targeting TLR4 mRNA, which was stable transfected into the human ovarian cancer cell line SKOV3 (MyD88-positive expression) and A2780 (MyD88-negative expression). Cell proliferation, cell cycle distribution and cell apoptosis were assessed in the cells transfected with scramble control shRNA (SKOV3/shControl, A2780/shControl) and TLR4 shRNA (SKOV3/shTLR4, A2780/shTLR4) to explore the possible functions of TLR4 in ovarian cancer cells growth. The expression of TLR4, MyD88, XIAP, Akt and pAkt was analysed by Western blot analysis. RESULTS: A knockdown of TLR4 levels down-regulated the expression of XIAP and pAkt. And it restored the inhibitory effect of paclitaxel on cell proliferation and impeding cell cycle progression in SKOV3 cells. CONCLUSIONS: It suggests that TLR4 negatively regulates paclitaxel chemotherapy and MyD88 is an essential downstream factor to TLR4 signalling for this resistance. Knockdown of TLR4 induces paclitaxel chemosensitivity which might depress the Akt pathway. The TLR4-MyD88 signalling represents an important source to promote tumour growth.

Triphalangeal thumb-polysyndactyly syndrome and syndactyly type IV are caused by genomic duplications involving the long range, limb-specific SHH enhancer.

BACKGROUND: The Sonic hedgehog (SHH) protein produced in the zone of polarising activity (ZPA) is a major determinant of the identity and numbers of digits in early limb development. Preaxial polydactyly types II (PPD2) and III (PPD3) have been mapped to a critical region at 7q36, and subsequently shown to be caused by point mutations in the ZPA regulatory sequence (ZRS), a long range cis-regulator for the SHH gene. Triphalangeal thumb-polysyndactyly syndrome (TPTPS) and syndactyly type IV (SD4) were also mapped to the 7q36 region but pathogenic mutations in ZRS have not yet been affirmed. METHODS AND RESULTS: We performed linkage and haplotype analysis in six Han Chinese families with TPTPS and/or SD4, and refined the disease locus to an interval of 646 kb containing ZRS. In all families, the affected individuals heterozygous at rs10254391 (a single nucleotide polymorphism within ZRS) revealed a remarkable allele imbalance on sequence chromatogram. Using real-time quantitative polymerase chain reaction (qPCR), we identified duplication of ZRS and found that this duplication segregated with the limb phenotypes in all families but was not detected in unaffected family members or in unrelated control individuals. The duplication was also confirmed by interphase fluorescence in situ hybridisation (FISH) in an affected individual. We designed 17 additional qPCR assays and defined the minimum duplications in all six families, ranging from 131kb to 398kb. CONCLUSION: Both TPTPS and SD4 are due to duplications involving ZRS, the limb specific SHH enhancer. Point mutations in the ZRS and duplications encompassing the ZRS cause distinctive limb phenotypes.

Inferring gene regulatory networks with time delays using a genetic algorithm.

Recently a state-space model with time delays for inferring gene regulatory networks was proposed. It was assumed that each regulation between two internal state variables had multiple time delays. This assumption caused underestimation of the model with many current gene expression datasets. In biological reality, one regulatory relationship may have just a single time delay, and not multiple time delays. This study employs Boolean variables to capture the existence of the time-delayed regulatory relationships in gene regulatory networks in terms of the state-space model. As the solution space of time delayed relationships is too large for an exhaustive search, a genetic algorithm (GA) is proposed to determine the optimal Boolean variables (the optimal time-delayed regulatory relationships). Coupled with the proposed GA, Bayesian information criterion (BIC) and probabilistic principle component analysis (PPCA) are employed to infer gene regulatory networks with time delays. Computational experiments are performed on two real gene expression datasets. The results show that the GA is effective at finding time-delayed regulatory relationships. Moreover, the inferred gene regulatory networks with time delays from the datasets improve the prediction accuracy and possess more of the expected properties of a real network, compared to a gene regulatory network without time delays.

Modeling gene expression from microarray expression data with state-space equations.

We describe a new method to model gene expression from time-course gene expression data. The modelling is in terms of state-space descriptions of linear systems. A cell can be considered to be a system where the behaviours (responses) of the cell depend completely on the current internal state plus any external inputs. The gene expression levels in the cell provide information about the behaviours of the cell. In previously proposed methods, genes were viewed as internal state variables of a cellular system and their expression levels were the values of the intemal state variables. This viewpoint has suffered from the underestimation of the model parameters. Instead, we view genes as the observation variables, whose expression values depend on the current intemal state variables and any external input. Factor analysis is used to identify the internal state variables, and Bayesian Information Criterion (BIC) is used to determine the number of the internal state variables. By building dynamic equations of the internal state variables and the relationships between the internal state variables and the observation variables (gene expression profiles), we get state-space descriptions of gene expression model. In the present method, model parameters may be unambiguously identified from time-course gene expression data. We apply the method to two time-course gene expression datasets to illustrate it.

[Repair of bedsores and ulcers with gluteus maximus musculocutaneous flap].

From 1984 to 1991, 5 cases of bedsores and 1 case of ulcer resulted from irradiation in gluteal region were repaired with gluteus maximus musculocutaneous flaps. All 5 cases of bedsores were the result of paraplegia. After a myocutaneous flap was transferred, the donor area was directly sutured without skin grafting. The excision wound in one patient reached 18 cm x 12 cm in size, however it was still repaired with total gluteus maximus musculocutaneous flap, and the donor area was also immediately closed with sutures. All of the patients were healed by first intention. For non-paraplegic patients it was deemed contra-indicated to use a total maximus gluteus musculocutaneous flap, and instead one half of the muscle was used, in order to avoid impairment of function of the hip joint.

White-light image processing using oriented speckle-screen encoding.

We present a new technique of spatially oriented speckle-screen encoding to improve on the grating encoding technique for white-light image processing.