[Similarities and differences of myocardial metabolic characteristics between HFpEF and HFrEF mice based on LC-MS/MS metabolomics].

Objective: To reveal the similarities and differences in myocardial metabolic characteristics between heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) mice using metabolomics. Methods: The experimental mice were divided into 4 groups, including control, HFpEF, sham and HFrEF groups (10 mice in each group). High fat diet and Nω-nitroarginine methyl ester hydrochloride (L-NAME) were applied to construct a"two-hit"HFpEF mouse model. Transverse aortic constriction (TAC) surgery was used to construct the HFrEF mouse model. The differential expression of metabolites in the myocardium of HFpEF and HFrEF mice was detected by untargeted metabolomics (UHPLC-QE-MS). Variable importance in projection>1 and P<0.05 were used as criteria to screen and classify the differentially expressed metabolites between the mice models. KEGG functional enrichment and pathway impact analysis demonstrated significantly altered metabolic pathways in both HFpEF and HFrEF mice. Results: One hundred and nine differentially expressed metabolites were detected in HFpEF mice, and 270 differentially expressed metabolites were detected in HFrEF mice. Compared with the control group, the most significantly changed metabolite in HFpEF mice was glycerophospholipids, while HFrEF mice presented with the largest proportion of carboxylic acids and their derivatives. KEGG enrichment and pathway impact analysis showed that the differentially expressed metabolites in HFpEF mice were mainly enriched in pathways such as biosynthesis of unsaturated fatty acids, ether lipid metabolism, amino sugar and nucleotide sugar metabolism, glycerophospholipid metabolism, arachidonic acid metabolism and arginine and proline metabolism. The differentially expressed metabolites in HFrEF mice were mainly enriched in arginine and proline metabolism, glycine, serine and threonine metabolism, pantothenate and CoA biosynthesis, glycerophospholipid metabolism, nicotinate and nicotinamide metabolism and arachidonic acid metabolism, etc. Conclusions: HFpEF mice have a significantly different myocardial metabolite expression profile compared with HFrEF mice. In addition, biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, glycerophospholipid metabolism and arginine and proline metabolism are significantly altered in both HFpEF and HFrEF mice, suggesting that these metabolic pathways may play an important role in disease progression in both types of heart failure.

Development of explicit formulations of G45-based gas kinetic scheme for simulation of continuum and rarefied flows.

In this work, the explicit formulations of the Grad's distribution function for the 45 moments (G45)-based gas kinetic scheme (GKS) are presented. Similar to the G13 function-based gas kinetic scheme (G13-GKS), G45-GKS simulates flows from the continuum regime to the rarefied regime by solving the macroscopic governing equations based on the conservation laws, which are widely used in conventional Navier-Stokes solver. These macroscopic governing equations are discretized by the finite volume method, where the numerical fluxes are evaluated by the local solution to the Boltzmann equation. The initial distribution function is reconstructed by the G45 distribution function, which is a higher order truncation of the Hermite expansion of distribution function compared with the G13 distribution function. Such high order truncation of Hermite expansion helps the present solver to achieve a better accuracy than G13-GKS. Moreover, the reconstruction of distribution function makes the development of explicit formulations of numerical fluxes feasible, and the evolution of the distribution function, which is the main reason why the discrete velocity method is expensive, is avoided. Several numerical experiments are performed to examine the accuracy of G45-GKS. Results show that the accuracy of the present solver for almost all flow problems is much better than G13-GKS. Moreover, some typical rarefied effects, such as the direction of heat flux without temperature gradients and thermal creep flow, can be well captured by the present solver.

Variant of gas kinetic flux solver for flows beyond Navier-Stokes level.

In this paper, a variant of gas kinetic flux solver (GKFS) is presented for simulation of flows beyond the Navier-Stokes (NS) level. The method retains the framework of GKFS and reconstructs the numerical fluxes by the moments of distribution function at the cell interface, which is given from the local solution of the Boltzmann equation. In the conventional GKFS, the first-order Chapman-Enskog (CE) expansion is utilized to approximate the initial distribution function. By using the differential chain rule, it was found that the CE expansion form could be linked to the stress tensor and the heat flux. For flows in the NS level, the stress tensor and heat flux can be simply calculated from the linearized constitutive relationship and Fourier's law, respectively. However, for flows beyond the NS level, due to the strong nonequilibrium effect, the linearized constitutive relationship and Fourier's law are insufficient to predict the stress tensor and the heat flux. To overcome this difficulty, this paper introduces correction terms to the stress tensor and heat flux in the initial distribution function. These correction terms will take effect in the strong nonequilibrium region for flows beyond the NS level. To avoid finding complex expressions or solving complicated partial differential equations for the correction terms, a simple and iterative procedure is proposed to update the correction terms based on the framework of GKFS. The proposed method is validated by three benchmark cases which cover the flow from the continuum regime to the transition regime. Numerical results show that the present solver can provide accurate solution in the continuum regime. It is indeed the correction terms that take effect in the strong nonequilibrium region for flows beyond the NS level, which enables the present solver to capture the nonequilibrium phenomenon with reasonable accuracy for rarefied flows at moderate Knudsen number.

[Clinical features and treatment outcome of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract].

Objective: To investigate the clinical features and prognosis of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract (extra-UADT NKTCL). Methods: The clinical data of 159 patients with extra-UADT NKTCL from the China Lymphoma Collaborative Group (CLCG) database between November 2001 and December 2015 were retrospectively analyzed. Kaplan-Meier survival analysis and Log-rank test were used to evaluate the prognosis. The Cox regression model is used for multi-factor analysis. Results: Extra-UADT NKTCL commonly occurs in skin and soft tissues (106/159, 66.7%) and gastrointestinal tract (31/159, 19.5%). The incidences of elevated lactate dehydrogenase (LDH) and Ann Arbor Ⅲ~Ⅳ stage were 47.8% (76/159) and 64.2% (102/159), respectively. The 3-year overall survival (OS) and progression-free survival (PFS) rates were 43.6% and 27.9%, respectively. The corresponding OS rates of primary skin/soft tissue site and gastrointestinal tract site were 41.0% and 59.4% (P=0.281), while the PFS rates were 24.8% and 48.3%, respectively (P=0.109). Combined modality treatment improved the 3-year OS of all the patients (58.4% vs 33.9%, P=0.001) and 3-year PFS (40.7% vs 20.7%, P=0.008) when compared with chemotherapy alone. LDH elevation, Ann Arbor synthesising and ≥2 junction external bits were intrusive as independent risk factors for total survival (P<0.05), LDH elevation and ≥2 junction outer bits were intrusive as independent risk factors for progressionless survival(P<0.05). The distant extranodal dissemination was the primary failure patterns. Conclusions: Extra-UADT NKTCL appears to have distinct clinical characteristics and poor outcome. Compared with chemotherapy alone, combined modality treatment may improve the prognosis of patients with extra-UADT NKTCL.

[Cost-effectiveness of primary prophylaxis with PEG-rhG-CSF in early-stage breast cancer patients receiving chemotherapy in China].

Objective: To evaluate the cost effectiveness of primary prophylaxis (PP) with pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF), PP with recombinant human granulocyte colony stimulating factor (rhG-CSF) and no prophylaxis in women with early-stage breast cancer in China. Methods: Two phase Markov models were constructed for a hypothetical cohort of patients aged 45 with stage Ⅱ breast cancer. The first phase modelled costs and outcomes of 4 cycles docetaxel combined with cyclophosphamide [TC×4, febrile neutropenia (FN) risk>20%] chemotherapy, which assumptions based on literature reviews, including FN rates [base-case (deterministic sensitivity analysis range), 0.29 (0.24-0.35)] and related events [FN case-fatality, 3.4 (2.7-4.1)]. Second phase modelled the long term survival which was link with the relative dose intensity (RDI) [mortality hazard ratio (HR) of RDI < 85% vs ≥85%, 1.45 (1.00-2.32)]. Clinical effectiveness, therapeutic costs, and economic utilities were estimated from peer-reviewed publications and expert opinions in case of unavailability of published evidences. Results: Compared to rhG-CSF PP and no prophylaxis, the cost of PEG-rhG-CSF PP increased to 5 208.19 RMB and 5 222.73 RMB, respectively. The quality-adjusted life-years (QALYs) enhanced to 0.066 and 0.297, respectively. Accordingly, the incremental cost effectiveness ratios (ICERs) are 79 146.3 RMB and 17 558.77 RMB per QALY, which were both below the willingness to pay (WTP) threshold of three times GDP per capita (18, 000 RMB) recommended by the WHO. Sensitivity analysis suggested that the more clinically effective the primary prophylaxis with PEG-rhG-CSF is, the more cost-effective primary prophylaxis with PEG-rhG-CSF will be. And the lower the mortality HR of RDI<85% vs ≥85% is, the more cost-effective primary prophylaxis with PEG-rhG-CSF will be. Conclusion: Although the cost of PP PEG-rhG-CSF is higher, considering the additional benefits, the administrating of PP PEG-rhG-CSF is likely to be a cost-effective alternative to PP rhG-CSF and no prophylaxis in patients with early stage breast cancer whose FN risks are more than 20% in China.

[Correlation of interleukin-4 gene methylation regulation with the pathogenesis of recurrent aphthous ulcer].

Objetive: To investigate whether the methylation patterns of the interleukin-4 (IL-4) gene promoter changed and whether environmental factors affected the methylation level of IL-4 gene in the peripheral blood of patients with recurrent aphthous ulcer (RAU). Methods: Totally 20 patients, who were diagnosed with RAU, were recruited from May 2018 to May 2019 in the Department of Stomatology， First Hospital of Shanxi Medical University in the study (RAU group), including 12 females and 8 males, with mean age of 16-35 years. During the same period, 20 healthy volunteers matching the age and gender of the RAU group were selected from the medical personnel of the same hospital as the healty control group, including 11 females and 9 males, with mean age of 15-35 years. Peripheral blood samples of two groups were collected and the methylation levels of the IL-4 promoter were detected by bisulfite sequencing PCR (BSP). The IL-4 promoter methylation level of each sample was analyzed by direct sequencing and the IL-4 mRNA level was detected by real-time quantitative PCR. The data obtained were statistically analyzed. Results: The IL-4 gene promoter fragment contained 10 CPG sites from -1400 to -1625 bp. The methylation rates of CPG(-1556), CPG(-1483), CPG(-1479)and 10 CPG sites were significantly higher in RAU group ï¼»(32.0±19.9)%, (53.0±13.4)%, (46.0±19.8)% and (39.3±12.4)%ï¼½ than in healthy control group ï¼»(20.0±3.2)%, (35.5±12.3)%, (28.0±14.4)% and (32.6±5.8)%ï¼½, with statistically significant differences (P<0.05). The relative expression of IL-4 mRNA in the peripheral blood of RAU patients (1.0±0.1) was significantly lower than that of the healthy control group (1.5±0.2) (P<0.01). There was a significant negative correlation between the overall methylation rate of IL-4 gene promoter and the relative expression level of IL-4 mRNA in RAU group (r=-0.494, P<0.05). In the multivariate analysis, smoking, vitamin B12 and folic acid in the RAU group were significantly correlated with the overall methylation rate of the IL-4 gene promoter (P<0.01). Conclusions: The hypermethylation of IL-4 promoter in RAU patients may be related to the reduction of IL-4 gene transcription. Vitamin B12, folic acid and smoking may affect IL-4 gene methylation in peripheral blood of RAU patients.

[Research progress of the relationship between liver regeneration and tumor recurrence after hepatectomy].

Partial hepatectomy is still the preferred modality of treatment for hepatocellular carcinoma.In recent years, a substantial number of in vivo and in vitro tests have been carried out to study how to promote postoperative liver regeneration in order to prevent the occurrence of small-for-size liver syndrome and liver failure. However, several studies have shown that the process of liver regeneration after hepatectomy can actually promote the growth of tumor cells and activate occult micro-focal lesions leading to tumor recurrence. Moreover, cytokines and genes which play crucial roles in the 3 stages of liver regeneration, are involved in the formation, migration, infiltration and recurrence of liver cancer to varying degrees. Achieving a balance between promotion of postoperative liver regeneration and inhibition of tumor recurrence has become a major problem in liver surgery.

[Clinical significance of NS1-BP expression in esophageal squamous cell carcinoma].

Objective: To investigate the clinical significance of NS1-BP expression in patients with esophageal squamous cell carcinoma (ESCC), and to study the roles of NS1-BP in proliferation and apoptosis of ESCC cells. Methods: A total of 98 tumor tissues and 30 adjacent normal tissues from 98 ESCC patients were used as study group and control group, and these samples were collected in Sun Yat-Sen University Cancer Center between 2002 and 2008. In addition, 46 ESCC tissues which were collected in Cancer Institute and Hospital of Tianjin Medical University were used as validation group. Expression of mucosal NS1-BP was detected by immunohistochemistry. Kaplan-Meier curve and log-rank test were used to analyze the survival rate. Multivariate Cox proportional hazard model was used to analyze the prognostic factors. Furthermore, NS1-BP was over expressed or knocked down in ESCC cells by transient transfection. Protein levels of c-Myc were detected by western blot. Cell viability and apoptosis was analyzed by MTT assay and flow cytometry. Results: Among all of tested samples, NS1-BP were down-regulated in 9 out of 30 non-tumorous normal esophageal tissues (30.0%) and 85 out of 144 ESCC tissues (59.0%), respectively, showing a statistically significant difference (P=0.012). In the study group, three-year disease-free survival rate of NS1-BP high expression group (53.2%) was significantly higher than that of NS1-BP low expression group (27.6%; P=0.009). In the validation group, the three-year disease-free survival rates were 57.8% and 25.5% in NS1-BP high and low levels groups, respectively, showing a similar results (P=0.016). Importantly, multivariate analyses showed that low expression of NS1-BP was an independent predictor for chemoradiotherapy sensitivity and shorter disease-free survival time in ESCC patients(P<0.05 for all). Furthermore, overexpressed NS1-BP in TE-1 cells repressed c-Myc expression, inhibited cell proliferation and promoted apoptosis. In contrast, knockdown NS1-BP in KYSE510 cells induced c-Myc expression, increased cell proliferation and repressed apoptosis. Conclusions: NS1-BP is an independent favorable prognostic factor in ESCC. It inhibits cell proliferation and enhances cell apoptosis via repressing c-Myc. Targeting NS1-BP may be a new therapeutic strategy for ESCC patients.

[Effect of radiation dose and dose rate on pulmonary fibrosis in mice].

OBJECTIVE: To study the effect of radiation dose and dose rate on radiation-induced pulmonary fibrosis in mice. METHODS: Twenty-four C57BL/6 mice were randomly divided into a control group (n=6) and an irradiation group(n=18). The irradiation group was further assigned to 3 subgroups according to the whole lung radiation with 15 Gy at 400 cGy/min, 20 Gy at 400 cGy/min and 20 Gy at 100 cGy/min, while the control group received sham-irradiation. All mice were scanned with computed tomograph (CT) 20 weeks post-irradiation, and then they were sacrificed and lung tissues were collected. H&E staining, sirius red staining, lung fibrosis scored and hydroxyproline content analysis were used to assess lung fibrosis and collagen deposition. Real time PCR was used to measure the mRNA expression of type Ⅰ collagen. Immunohistochemical staining was used to detect the activatin and distribution of a-SMA(+) -myofibroblasts. RESULTS: Compared to the control group, mice from irradiation groups exhibited significant pulmonary consolidation and collagen deposition.At the same dose rate, the higher irradiated dose used, the more severe pulmonary fibrosis was.On the other hand, with the same dose, the dose rate had less effect on pulmonary fibrosis. CONCLUSION: The effect of radiation dose on the degree of pulmonary fibrosis in mice is more than effect of the dose rate.

Prognostic nomogram for overall survival in previously untreated patients with extranodal NK/T-cell lymphoma, nasal-type: a multicenter study.

The aim of this study was to develop a widely accepted prognostic nomogram for extranodal NK/T-cell lymphoma, nasal-type (NKTCL). The clinical data from 1383 patients with NKTCL treated at 10 participating institutions between 2000 and 2011 were reviewed. A nomogram was developed that predicted overall survival (OS) based on the Cox proportional hazards model. To contrast the utility of the nomogram against the widely used Ann Arbor staging system, the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI), we used the concordance index (C-index) and a calibration curve to determine its predictive and discriminatory capacity. The 5-year OS rate was 60.3% for the entire group. The nomogram included five important variables based on a multivariate analysis of the primary cohort: stage; age; Eastern Cooperative Oncology Group performance status; lactate dehydrogenase; and primary tumor invasion. The calibration curve showed that the nomogram was able to predict 5-year OS accurately. The C-index of the nomogram for OS prediction was 0.72 for both cohorts, which was superior to the predictive power (range, 0.56-0.64) of the Ann Arbor stage, IPI and KPI in the primary and validation cohorts. The proposed nomogram provides an individualized risk estimate of OS in patients with NKTCL.

Effect of salt intake and potassium supplementation on brachial-ankle pulse wave velocity in Chinese subjects: an interventional study

Accumulating evidence has suggested that high salt and potassium might be associated with vascular function. The aim of this study was to investigate the effect of salt intake and potassium supplementation on brachial-ankle pulse wave velocity (PWV) in Chinese subjects. Forty-nine subjects (28-65 years of age) were selected from a rural community of northern China. All subjects were sequentially maintained on a low-salt diet for 7 days (3.0 g/day NaCl), a high-salt diet for an additional 7 days (18.0 g/day NaCl), and a high-salt diet with potassium supplementation for a final 7 days (18.0 g/day NaCl+4.5 g/day KCl). Brachial-ankle PWV was measured at baseline and on the last day of each intervention. Blood pressure levels were significantly increased from the low-salt to high-salt diet, and decreased from the high-salt diet to high-salt plus potassium supplementation. Baseline brachial-ankle PWV in salt-sensitive subjects was significantly higher than in salt-resistant subjects. There was no significant change in brachial-ankle PWV among the 3 intervention periods in salt-sensitive, salt-resistant, or total subjects. No significant correlations were found between brachial-ankle PWV and 24-h sodium and potassium excretions. Our study indicates that dietary salt intake and potassium supplementation, at least in the short term, had no significant effect on brachial-ankle PWV in Chinese subjects.

Inhibition of human positive cofactor 4 radiosensitizes human esophageal squmaous cell carcinoma cells by suppressing XLF-mediated nonhomologous end joining.

Radiotherapy has the widest application to esophageal squamous cell carcinoma (ESCC) patients. Factors associated with DNA damage repair have been shown to function in cell radiosensitivity. Human positive cofactor 4 (PC4) has a role in nonhomologous end joining (NHEJ) and is involved in DNA damage repair. However, the clinical significance and biological role of PC4 in cancer progression and cancer cellular responses to chemoradiotherapy (CRT) remain largely unknown. The aim of the present study was to investigate the potential roles of PC4 in the radiosensitivity of ESCC. In this study, we showed that knockdown of PC4 substantially increased ESCC cell sensitivity to ionizing radiation (IR) both in vitro and in vivo and enhanced radiation-induced apoptosis and mitotic catastrophe (MC). Importantly, we demonstrated that silencing of PC4 suppressed NHEJ by downregulating the expression of XLF in ESCC cells, whereas reconstituting the expression of XLF protein in the PC4-knockdown ESCC cells restored NHEJ activity and radioresistance. Moreover, high expression of PC4 positively correlated with ESCC resistance to CRT and was an independent predictor for short disease-specific survival of ESCC patients in both of our cohorts. These findings suggest that PC4 protects ESCC cells from IR-induced death by enhancing the NHEJ-promoting activity of XLF and could be used as a novel radiosensitivity predictor and a promising therapeutic target for ESCCs.

Simultaneous integrated boost intensity-modulated radiotherapy for treatment of locally advanced non-small-cell lung cancer: a retrospective clinical study.

OBJECTIVE: To evaluate the clinical efficacy and safety of simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) for patients with locally advanced non-small-cell lung cancer (LANSCLC). METHODS: 48 patients with LANSCLC treated with SIB-IMRT from January 2010 to April 2012 were retrospectively analysed. A radiation dose of 45-63 Gy (median dose, 51.58 Gy) was delivered to the planning target volume (1.8-2.0 Gy daily fractions) simultaneously with 55.0-74.2 Gy (median dose, 63 Gy) to the planning gross tumour volume (2.00-2.25 Gy daily fractions). 45 patients received concurrent/sequential chemotherapy. The overall survival (OS), locoregional recurrence-free survival (LRFS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Treatment-related pneumonitis and oesophagitis were graded according to the Common Terminology Criteria for Adverse Events v. 4.0. RESULTS: By 1 July 2013, 29 of the 48 patients were dead. The median follow-up time for the survivors was 28 months (19-44 months). The median OS and PFS were 21 and 14 months, respectively. The median LRFS time was not reached. The 2-year LRFS, OS and PFS were 62.5%, 45.1% and 28.0%, respectively. Two patients experienced Grade 3 treatment-related pneumonitis, two patients experienced Grade 5 treatment-related pneumonitis and two patients had ≥Grade 3 oesophagitis. CONCLUSION: SIB-IMRT appears to be an effective therapeutic option in patients with LANSCLC and warrants further evaluation with increased number of patients in prospective clinical trials. ADVANCES IN KNOWLEDGE: This study explores the feasibility of delivering tumoricidal doses of radiation to primary lesions in non-small-cell lung cancer.

Benefits of postoperative radiotherapy in multimodality treatment of resected small-cell lung cancer with lymph node metastasis.

AIM: The purpose of this study is to evaluate the role of postoperative radiotherapy (PORT) in resected small-cell lung cancer (SCLC). METHODS: This study retrospectively analyzed 143 patients with completely resected SCLC in our institution between 1996 and 2011. The primary endpoint was overall survival (OS). The log-rank test and Cox regression model were used to evaluate the factors influencing local-regional recurrence (LRR) and OS. RESULTS: The median OS for the entire population was 34 months, and the 5-year OS rate was 34.6%. In multivariate analysis, age, surgical procedure, pathology stage, adjuvant chemotherapy and distant relapse were significant factors for survival. For the whole population, PORT had no effect on OS, with a median OS of 40 months in the PORT group versus 27 months in the non-PORT group (p = 0.260). However, in patients with N1 disease, the median OS were 40 months in the PORT group versus 14 months in the non-PORT group (p = 0.032). The corresponding OS in N2 patients were 35 months versus 17 months, respectively (p = 0.040). Similarly, PORT significantly reduced the LRR in patients with positive lymph node. For patients with N1 disease, the 3-year LRR rate was 0.0% in the PORT group versus 14.3% in the non-PORT group (p = 0.037). The corresponding LLR rate in N2 patients was 4.2% versus 56.6% (p < 0.001). CONCLUSION: PORT significantly reduced LRR and improved OS in patients with regional metastasis SCLC. We suggest supplementing PORT in the multimodality treatment of resected SCLC with lymph node metastasis.

Salt-induced epithelial-to-mesenchymal transition in Dahl salt-sensitive rats is dependent on elevated blood pressure

Dietary salt intake has been linked to hypertension and cardiovascular disease. Accumulating evidence has indicated that salt-sensitive individuals on high salt intake are more likely to develop renal fibrosis. Epithelial-to-mesenchymal transition (EMT) participates in the development and progression of renal fibrosis in humans and animals. The objective of this study was to investigate the impact of a high-salt diet on EMT in Dahl salt-sensitive (SS) rats. Twenty-four male SS and consomic SS-13BN rats were randomized to a normal diet or a high-salt diet. After 4 weeks, systolic blood pressure (SBP) and albuminuria were analyzed, and renal fibrosis was histopathologically evaluated. Tubular EMT was evaluated using immunohistochemistry and real-time PCR with E-cadherin and alpha smooth muscle actin (α-SMA). After 4 weeks, SBP and albuminuria were significantly increased in the SS high-salt group compared with the normal diet group. Dietary salt intake induced renal fibrosis and tubular EMT as identified by reduced expression of E-cadherin and enhanced expression of α-SMA in SS rats. Both blood pressure and renal interstitial fibrosis were negatively correlated with E-cadherin but positively correlated with α-SMA. Salt intake induced tubular EMT and renal injury in SS rats, and this relationship might depend on the increase in blood pressure.

Clinical observation on the efficacy of CyberKnife for primary or metastatic retroperitoneal tumours.

The aim of the paper is to evaluate the efficacy of CyberKnife® for the treatment of primary or metastatic retroperitoneal tumours. Twenty-eight patients were treated. The prescription isodose line (median, 78%; range, 70-84%) covered the planning target volume at a total dose of 2000-6000 cGy (median, 4500 cGy) and a biologically effective dose of 3750-10,080 cGy (median, 7680 cGy) in 2-10 fractions (median, five fractions). The results showed that the complete response, partial response, stable disease, and progressive disease rates were 43% (12/28), 36% (10/28), 18% (5/28), and 4% (1/28) respectively. The overall response rate was 96%. The 1-, 2- and 3-year local control rates were 92%, 86%, and 86% respectively. The 1-, 2- and 3-year overall survival rates were 60%, 49%, and 49% respectively. No significant difference was found between local progression-free survival and overall survival. Moreover, if a patient only had metastases in the retroperitoneum and local control was effective, there was no significant difference between local progression-free survival and overall progression-free survival. In conclusion, CyberKnife treatment for retroperitoneal tumours resulted in high response rates with minimal side effects. All radiation-induced side effects were well tolerated.

Efficacy and tolerability of toremifene and tamoxifen therapy in premenopausal patients with operable breast cancer: a retrospective analysis.

BACKGROUND: Given the use of tamoxifen as standard treatment for hormone receptor-positive breast cancer, the use of toremifene as an adjuvant endocrine therapy has not been widely examined. The present retrospective study compared the efficacy and safety of toremifene and tamoxifen in the treatment of operable hormone receptor-positive breast cancer in premenopausal women. METHODS: Premenopausal patients with hormone receptor- positive operable breast cancer were eligible. Enrolled patients (n = 1847) received either 60 mg toremifene (n = 396) or 20 mg tamoxifen (n = 1451) daily for a minimum of 5 years after surgery. Disease-free survival (dfs) was the primary endpoint. Overall survival (os) and time to distant recurrence were secondary endpoints. RESULTS: Treatment with toremifene and tamoxifen resulted in no between-group differences in dfs (p = 0.659) or os (p = 0.364). Mean dfs was 10.3 years for both groups. Mean os was 11.2 years for the toremifene group and 11.1 years for tamoxifen group. The 5-year dfs rate was 87.0% in the toremifene group and 85.0% in the tamoxifen group. The 5-year survival rate was 94.3% in the toremifene group and 93.5% in the tamoxifen group. Adverse events rates were similar in the two groups, with the exception of irregular menses, which occurred at a higher rate in the tamoxifen group than in the toremifene group (10.0% vs. 6.3%, p = 0.025). CONCLUSIONS: In this retrospective study, the efficacy and safety profiles of toremifene and tamoxifen for the treatment of operable hormone receptor-positive breast cancer in premenopausal women were similar.

A preliminary probe into the movement of pancreatic lesions and factors that influence it.

The aim of this study was to investigate the movement, and the factors that influence such movement, of pancreatic lesions and to provide a reference for determination of planning target volume (PTV) during stereotactic radiotherapy. We implanted 19 gold markers into the inner pancreatic tumours of 16 pancreatic carcinoma patients percutaneously under B-ultrasonographic guidance. The marked motion of pancreatic lesions in the x (right-left), y (superoinferior) and z (anteroposterior) directions was measured using an X-ray simulator system. Based on the statistical analysis of the detected movements, we investigated the relevant influencing factors of pancreatic lesions with multinomial linear regression. Data showed that the mean motion amplitudes of pancreatic lesions were 0.16 cm +/- 0.06 (range 0.1-0.3 cm) in the x direction, 0.25 cm +/- 0.12 (range 0.1-0.4 cm) in the y direction and 0.88 cm +/- 0.24 (0.5-1.6 cm) in the z direction. Motion amplitude was not correlated with the height, weight or age of the patients nor with the location or size of the tumour. The motion of pancreatic lesions was mainly influenced by the respiratory motion and has maximal amplitude in the z direction. Therefore, motion in the z direction should be given a priority consideration while determining the PTV.

PCR Based Cloning and Sequence Analysis of the Pichia pastoris Cystathionine beta-Synthase Gene.

The cystathionine beta-Synthase (CBS) gene of Pichia pastoris has been cloned by homology to the CBS gene of Saccharomyces cerevisiae. First, based on the homology alignment of CBS genes from different sources, a pair of degenerate PCR primers were designed to amplify a conservative fragment of Pichia pastoris CBS gene. After the sequence was revealed, 5' RACE and 3' RACE were performed separately. The whole sequence of Pichia pasotris CBS gene was assembled. This gene encodes a polypeptide of 501 residues. Comparison of deduced amino acid sequence of this new gene with that of S. cerevisiae CBS showed 54% identity. Disruption of CBS gene resulted in a Cys(-) auxotrophy in Pichia pastoris. Thesequence was submitted to GenBank/EMBL/DDBJ under Accession No.AF367364.