Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first line treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma: RATIONALE-305 randomised, double blind, phase 3 trial.

OBJECTIVE: To evaluate the efficacy and safety of tislelizumab added to chemotherapy as first line (primary) treatment for advanced gastric or gastro-oesophageal junction adenocarcinoma compared with placebo plus chemotherapy. DESIGN: Randomised, double blind, placebo controlled, phase 3 study. SETTING: 146 medical centres across Asia, Europe, and North America, between 13 December 2018 and 28 February 2023. PARTICIPANTS: 1657 patients aged ≥18 years with human epidermal growth factor receptor 2 negative locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma, regardless of programmed death-ligand 1 (PD-L1) expression status, who had not received systemic anticancer therapy for advanced disease. INTERVENTIONS: Patients were randomly (1:1) assigned to receive either tislelizumab 200 mg or placebo intravenously every three weeks in combination with chemotherapy (investigator's choice of oxaliplatin and capecitabine, or cisplatin and 5-fluorouracil) and stratified by region, PD-L1 expression, presence or absence of peritoneal metastases, and investigator's choice of chemotherapy. Treatment continued until disease progression or unacceptable toxicity. MAIN OUTCOME MEASURES: The primary endpoint was overall survival, both in patients with a PD-L1 tumour area positivity (TAP) score of ≥5% and in all randomised patients. Safety was assessed in all those who received at least one dose of study treatment. RESULTS: Of 1657 patients screened between 13 December 2018 and 9 February 2021, 660 were ineligible due to not meeting the eligibility criteria, withdrawal of consent, adverse events, or other reasons. Overall, 997 were randomly assigned to receive tislelizumab plus chemotherapy (n=501) or placebo plus chemotherapy (n=496). Tislelizumab plus chemotherapy showed statistically significant improvements in overall survival versus placebo plus chemotherapy in patients with a PD-L1 TAP score of ≥5% (median 17.2 months v 12.6 months; hazard ratio 0.74 (95% confidence interval 0.59 to 0.94); P=0.006 (interim analysis)) and in all randomised patients (median 15.0 months v 12.9 months; hazard ratio 0.80 (0.70 to 0.92); P=0.001 (final analysis)). Grade 3 or worse treatment related adverse events were observed in 54% (268/498) of patients in the tislelizumab plus chemotherapy arm versus 50% (246/494) in the placebo plus chemotherapy arm. CONCLUSIONS: Tislelizumab added to chemotherapy as primary treatment for advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma provided superior overall survival with a manageable safety profile versus placebo plus chemotherapy in patients with a PD-L1 TAP score of ≥5%, and in all randomised patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03777657.

Second-line tislelizumab versus chemotherapy in Japanese patients with advanced or metastatic esophageal squamous cell carcinoma: subgroup analysis from RATIONALE-302.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) has a poor prognosis, with limited second-line systemic therapy options, and represents an increasing disease burden in Japan. In the phase 3 RATIONALE-302 study, the anti-programmed cell death protein 1 antibody, tislelizumab, significantly improved overall survival (OS) versus chemotherapy as second-line treatment for advanced/metastatic ESCC. Here, we report the Japanese patient subgroup results. METHODS: Patients with advanced/metastatic ESCC, with disease progression during/after first-line systemic therapy were randomized 1:1 to open-label tislelizumab 200 mg every 3 weeks or investigator's choice of chemotherapy (paclitaxel/docetaxel). Efficacy and safety were assessed in all randomized Japanese patients. RESULTS: The Japanese subgroup comprised 50 patients (n = 25 per arm). Tislelizumab improved OS versus chemotherapy (median: 9.8 vs. 7.6 months; HR 0.59; 95% CI 0.31, 1.12). Among patients with programmed death-ligand 1 score ≥ 10%, median OS was 12.5 months with tislelizumab (n = 10) versus 2.9 months with chemotherapy (n = 6) (HR 0.31; 95% CI 0.09, 1.03). Tislelizumab improved progression-free survival versus chemotherapy (median: 3.6 vs. 1.7 months, respectively; HR 0.50; 95% CI 0.27, 0.95). Objective response rate was greater with tislelizumab (32.0%) versus chemotherapy (20.0%), and responses were more durable (median duration of response: 8.8 vs. 2.6 months, respectively). Fewer patients experienced ≥ grade 3 treatment-related adverse events with tislelizumab (24.0%) versus chemotherapy (47.8%). Tislelizumab demonstrated an improvement in health-related quality of life versus chemotherapy. CONCLUSIONS: As second-line therapy for advanced/metastatic ESCC, tislelizumab improved OS versus chemotherapy, with a favorable safety profile, in the Japanese patient subgroup, consistent with the overall population. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov: NCT03430843.

Evaluation of lifestyle behaviors, anxiety and depression in patients with hematologic disorders.

Patients with hematologic disorders may experience anxiety and depression due to their immunocompromised status and potential side effects of therapies. Healthy lifestyle behaviors might enhance the mental health. To evaluate the association of both separate and clustering pattern lifestyle behaviors with anxiety and depression in hematological patients, healthcare providers can develop future initiatives that respond to the specific needs of this population. A total of 185 patients with hematologic disorders were enrolled in this cross-sectional study. Linear regression analysis was performed to measure the association of separate lifestyles with anxiety and depression. Latent class analysis was further conducted to identify homogeneous and mutually exclusive lifestyle classes, and the logistic regression was then used to assess the relationship between class memberships and symptoms of anxiety and depression. The study found sleep quality was correlated with anxiety and depression. Nevertheless, no association of anxious and depressive symptoms with sitting and exercise, dietary habits, toxicant exposure, drinking, and smoking, in either the overall patient population or patients classified by hematologic neoplasms. Two latent classes of lifestyle behaviors were further identified, but the class memberships were independent of anxiety and depression. The study suggested that promoting sleep quality was a viable intervention for patients with hematologic disorders. However, the clustering pattern of lifestyles may not be a reliable indicator of psychological issues.

Benign prostatic hyperplasia associated with white matter hyperintensities in men.

PURPOSE: Benign prostatic hyperplasia (BPH) describes common noncancerous prostate enlargement. BPH is usually associated with lower urinary tract symptoms and an increased risk of cerebrovascular diseases, such as stroke and its recurrence. White matter hyperintensities (WMHs), markers of cerebral injury, increase the risk of stroke, cognitive impairment, dementia, and death. The relationship between BPH and WMHs remains unclear. This study aimed to determine the association between BPH and WMHs. METHODS: A total of 788 male patients from the First Affiliated Hospital of Kunming Medical University from July 2019 to September 2021 were enrolled in this cross-sectional study. BPH was assessed by abdominal ultrasound, and three independent neuroradiologists rated the presence or absence of WMHs. Multiple imputations of chained equations were used to handle missing data. Logistic regression was used to assess the relationship between BPH and WMHs. RESULTS: Patients with BPH presented an increased risk of WMHs with a crude odds ratio (OR) of 2.76 (95% CI, 2.02-3.79) and an adjusted OR of 1.75 (95% CI, 1.24-2.48) after controlling for potential confounding factors in the multivariate logistic regression. CONCLUSION: We found that BPH was closely associated with WMHs in male Chinese individuals.

Tislelizumab plus chemotherapy versus placebo plus chemotherapy as first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma (RATIONALE-306): a global, randomised, placebo-controlled, phase 3 study.

BACKGROUND: The options for first-line treatment of advanced oesophageal squamous cell carcinoma are scarce, and the outcomes remain poor. The anti-PD-1 antibody, tislelizumab, has shown antitumour activity in previously treated patients with advanced oesophageal squamous cell carcinoma. We report interim analysis results from the RATIONALE-306 study, which aimed to assess tislelizumab plus chemotherapy versus placebo plus chemotherapy as first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma. METHODS: This global, randomised, double-blind, parallel-arm, placebo-controlled, phase 3 study was conducted at 162 medical centres across Asia, Europe, Oceania, and North America. Patients (aged ≥18 years) with unresectable, locally advanced, recurrent or metastatic oesophageal squamous cell carcinoma (regardless of PD-L1 expression), Eastern Cooperative Oncology Group performance status of 0-1, and measurable or evaluable disease per Response Evaluation Criteria in Solid Tumours (version 1.1) were recruited. Patients were randomly assigned (1:1), using permuted block randomisation (block size of four) and stratified by investigator-chosen chemotherapy, region, and previous definitive therapy, to tislelizumab 200 mg or placebo intravenously every 3 weeks on day 1, together with an investigator-chosen chemotherapy doublet, comprising a platinum agent (cisplatin 60-80 mg/m2 intravenously on day 1 or oxaliplatin 130 mg/m2 intravenously on day 1) plus a fluoropyrimidine (fluorouracil [750-800 mg/m2 intravenously on days 1-5] or capecitabine [1000 mg/m2 orally twice daily on days 1-14]) or paclitaxel (175 mg/m2 intravenously on day 1). Treatment was continued until disease progression or unacceptable toxicity. Investigators, patients, and sponsor staff or designees were masked to treatment. The primary endpoint was overall survival. The efficacy analysis was done in the intention-to-treat population (ie, all randomly assigned patients) and safety was assessed in all patients who received at least one dose of study treatment. The trial is registered with ClinicalTrials.gov, NCT03783442. FINDINGS: Between Dec 12, 2018, and Nov 24, 2020, 869 patients were screened, of whom 649 were randomly assigned to tislelizumab plus chemotherapy (n=326) or placebo plus chemotherapy (n=323). Median age was 64·0 years (IQR 59·0-69·0), 563 (87%) of 649 participants were male, 86 (13%) were female, 486 (75%) were Asian, and 155 (24%) were White. 324 (99%) of 326 patients in the tislelizumab group and 321 (99%) of 323 in the placebo group received at least one dose of the study drug. As of data cutoff (Feb 28, 2022), median follow-up was 16·3 months (IQR 8·6-21·8) in the tislelizumab group and 9·8 months (IQR 5·8-19·0) in the placebo group, and 196 (60%) of 326 patients in the tislelizumab group versus 226 (70%) of 323 in the placebo group had died. Median overall survival in the tislelizumab group was 17·2 months (95% CI 15·8-20·1) and in the placebo group was 10·6 months (9·3-12·1; stratified hazard ratio 0·66 [95% CI 0·54-0·80]; one-sided p<0·0001). 313 (97%) of 324 patients in the tislelizumab group and 309 (96%) of 321 in the placebo group had treatment-related treatment-emergent adverse events. The most common grade 3 or 4 treatment-related treatment-emergent adverse events were decreased neutrophil count (99 [31%] in the tislelizumab group vs 105 [33%] in the placebo group), decreased white blood cell count (35 [11%] vs 50 [16%]), and anaemia (47 [15%] vs 41 [13%]). Six deaths in the tislelizumab group (gastrointestinal and upper gastrointestinal haemorrhage [n=2], myocarditis [n=1], pulmonary tuberculosis [n=1], electrolyte imbalance [n=1], and respiratory failure [n=1]) and four deaths in the placebo group (pneumonia [n=1], septic shock [n=1], and unspecified death [n=2]) were determined to be treatment-related. INTERPRETATION: Tislelizumab plus chemotherapy as a first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma provided superior overall survival with a manageable safety profile versus placebo plus chemotherapy. Given that the interim analysis met its superiority boundary for the primary endpoint, as confirmed by the independent data monitoring committee, this Article represents the primary study analysis. FUNDING: BeiGene.

Association of lifestyle behaviors with health-related quality of life among patients with hematologic diseases.

PURPOSE: Health-related quality of life (HRQoL) is a multi-dimensional construct used to assess the impact of health status on quality of life, and it is known to be affected by lifestyle behaviors. This study focused on multiple lifestyle behaviors among patients with hematologic diseases, including physical activity, dietary intake, sleep quality, occupational exposure, alcohol consumption and smoking. The main objective was to investigate the association of both individual and clustering of health behaviors with HRQoL among the population with hematologic diseases based on a comprehensive lifestyle survey. METHODS: A total of 539 patients with hematologic diseases aged over 18 years were enrolled in this cross-sectional study. Latent class analysis was used to identify homogeneous, mutually exclusive lifestyle classes, and multinomial logistic regression was then performed to explore the association of lifestyle classes membership with HRQoL. Meanwhile, multiple linear regression and quantile regression were used to identify the relationship between individual lifestyle behaviors and HRQoL. RESULTS: A three-class model was selected based on conceptual interpretation and model fit. We found no association between multiple lifestyle behaviors and HRQoL in the 3-class model, either in the whole patients or in subgroups stratified by hematological malignancies. Further research on each lifestyle found that physical activity, dietary intake, occupational exposure, alcohol consumption or smoking were independent of HRQoL. Sleep quality was positively associated with HRQoL. CONCLUSION: Our findings suggested that clustering of lifestyle behaviors may not be an indicator to reflect the health quality of patients with hematologic diseases. Sleep represents a viable intervention target that can confer health benefits on the hematologic patients.

Tislelizumab Versus Chemotherapy as Second-Line Treatment for Advanced or Metastatic Esophageal Squamous Cell Carcinoma (RATIONALE-302): A Randomized Phase III Study.

PURPOSE: Patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) have poor prognosis. For these patients, treatment options are limited after first-line systemic therapy. PATIENTS AND METHODS: In this open-label phase III clinical study, patients with advanced or metastatic ESCC, whose tumor progressed after first-line systemic treatment, were randomly assigned (1:1) to receive intravenous tislelizumab, an anti-programmed cell death protein 1 antibody, 200 mg every 3 weeks or chemotherapy (investigator's choice of paclitaxel, docetaxel, or irinotecan). The primary end point was overall survival (OS) in all patients. The key secondary end point was OS in patients with programmed death-ligand 1 tumor area positivity (TAP) score ≥ 10%. RESULTS: In total, 512 patients across 11 countries/regions were randomly assigned. At final analysis, conducted after 410 death events occurred, OS was significantly longer with tislelizumab versus chemotherapy in all patients (median, 8.6 v 6.3 months; hazard ratio [HR], 0.70 [95% CI, 0.57 to 0.85]; one-sided P = .0001), and in patients with TAP ≥ 10% (median, 10.3 months v 6.8 months; HR, 0.54 [95% CI, 0.36 to 0.79]; one-sided P = .0006). Survival benefit was consistently observed across all predefined subgroups, including those defined by baseline TAP score, region, and race. Treatment with tislelizumab was associated with higher objective response rate (20.3% v 9.8%) and a more durable antitumor response (median, 7.1 months v 4.0 months) versus chemotherapy in all patients. Fewer patients experienced ≥ grade 3 treatment-related adverse events (18.8% v 55.8%) with tislelizumab versus chemotherapy. CONCLUSION: Tislelizumab significantly improved OS compared with chemotherapy as second-line therapy in patients with advanced or metastatic ESCC, with a tolerable safety profile. Patients with programmed death-ligand 1 TAP ≥ 10% also demonstrated statistically significant survival benefit with tislelizumab versus chemotherapy.

RATIONALE 311: tislelizumab plus concurrent chemoradiotherapy for localized esophageal squamous cell carcinoma.

Definitive chemoradiotherapy is the standard of care for inoperable locoregionally advanced esophageal squamous cell carcinoma (ESCC). Immune checkpoint inhibitors such as anti-PD-1/PD-L1 antibodies have led to a paradigm shift in advanced, metastatic ESCC treatment; however, the effect of incorporating checkpoint inhibitors in the definitive management of ESCC is unclear. Tislelizumab is an anti-PD-1 antibody specifically engineered to minimize FcÉ£R binding on macrophages to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. The RATIONALE 311 study described here (BGB-A317-311; NCT03957590) is a registrational multicenter, double-blind, placebo-controlled, randomized, Phase III clinical trial designed to evaluate the efficacy and safety of tislelizumab combined with concurrent chemoradiotherapy in patients with inoperable localized ESCC.

Lay abstract Esophageal cancer is a challenging disease that seriously threatens patients' health and life. Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal cancer. Most patients who have inoperable stage II­IV ESCC are currently treated with a sequential combination of chemotherapy and radiation therapy, with the hopes of increasing the positive effects seen from either therapy alone. Immune checkpoint inhibitors such as anti-PD-1/PD-L1 antibodies have shown encouraging results in patients with ESCC, but it is not known if combining checkpoint inhibitors with simultaneous chemotherapy and radiation therapy will provide additional benefits. The safety and efficacy of tislelizumab, an anti-PD-1 antibody specifically engineered to limit potential resistance to anti-PD-1 therapy, is being investigated in combination with simultaneous chemotherapy and radiation therapy in patients with inoperable stage II­IV ESCC in an actively enrolling clinical trial, RATIONALE 311 (NCT03957590). Our trial in progress article explains the reason RATIONALE 311 was started and provides important enrollment information for doctors. Clinical trial registration: NCT03957590 (ClinicalTrials.gov).

Aberrant expression of the UPF1 RNA surveillance gene disturbs keratinocyte homeostasis by stabilizing AREG.

The up­frameshift suppressor 1 homolog (UPF1) RNA surveillance gene is a core element in the nonsense­mediated RNA decay (NMD) pathway, which impacts a broad spectrum of biological processes in a cell­specific manner. In the present study, the contribution of the NMD pathway to psoriasis lesions and its moderating effects on the biological processes of keratinocytes was reported. Sanger sequencing for skin scales from two patients with psoriasis identified two mRNA mutations (c.2935_2936insA and c.2030­2081del) in the UPF1 gene. The somatic mutants produced truncated UPF1 proteins and perturbed the NMD pathway in cells, leading to the upregulation of NMD substrates. As the most abundant epidermal growth factor receptor ligand in keratinocytes, it was concluded that amphiregulin (AREG) mRNA is a natural NMD substrate, that is dependent on its 3' untranslated region sequence. Perturbed NMD modulated keratinocyte homeostasis in an AREG­dependent but nonidentical manner, which highlighted the unique characteristics of NMD in keratinocytes. By targeting AREG mRNA post­transcriptionally, the UPF1­NMD pathway contributed to an imbalance between proliferation on the one hand, and apoptosis and abnormal differentiation, migration and inflammatory response on the other, in keratinocytes, which indicated a role of the NMD pathway in the full development of keratinocyte­related morbidity and skin diseases.

[Site-directed mutagenesis of human IL-29 and antineoplastic activity of the recombinant human IL-29 variant].

To explore the anti-tumor proliferation activity of human interleukin-29 (hIL-29) variant and based on bioinformatics analyzed data of hIL-29, a mutant gene hIL-29(mut33,35) was amplified by site-directed mutagenesis and megaprimer PCR. The hIL-29(mut33,35) was inserted into an eukaryotic expression plasmid pPIC9K and successfully expressed in Pichia pastoris GS115. A recombinant variant protein (rhIL-29(mut33,35)) was purified from the ferment supernatant of the engineering GS115. To observe the antineoplastic activity of the variant rhIL-29(mut33,35), a CCK-8 reagent was used to detect the anti-proliferation effect. Results show that it has strong anti-proliferation effect when acted on liver cancer cell BEL7402, colon cancer cell HCT8 and gastric cancer cell SGC7901. The inhibition ratios of the three tumor cells were (30.99 ± 1.58)%, (22.47 ± 1.37)% and (32.05 ± 2.02)%, respectively. In high dose group, the anti-proliferation effect of the rhIL-29(mut33,35) was stronger than that of wild type rhIL-29 (P < 0.01). This indicates the variant rhIL-29(mut33,35) has potential development value for medicine.

Prevalence and risk factors for COPD in greenhouse farmers: a large, cross-sectional survey of 5,880 farmers from northeast China.

BACKGROUND: COPD is one of the most common chronic diseases, and more and more farmers who were frequently exposed to greenhouse environments were diagnosed with COPD. However, little information is available on the prevalence of COPD among the greenhouse farmers. This study was conducted to assess the prevalence of COPD and investigate the potential risk factors for COPD among the Chinese greenhouse farmers. METHODS: Cross-sectional studies involving a sample of greenhouse farmers living in northeast China were performed via stratified-cluster-random sampling. All subjects were interviewed using a uniform questionnaire and underwent pulmonary function tests between 2006 and 2009, based on the diagnostic criteria of the Global Initiative for Chronic Obstructive Lung Disease. Multiple logistic regression analysis was conducted to examine the risk factors for COPD. RESULTS: Of the 5,880 greenhouse farmers from northeast China who were originally selected for this study, 5,420 questionnaires were completed. The overall prevalence of COPD in greenhouse farmers was 17.5%. The COPD prevalence was significantly higher in elderly subjects (≥50 years), current smokers, in those with lower body mass index (≤18.5 kg/m(2)) and less education, in those who were exposed to mushroom, flowers and poultry, and in those living in mountain and coastal region. Multiple logistic regression analysis revealed that age over 50 years old (odds ratio [OR]=298.69, 95% confidence interval [CI]=121.57-733.84), smoking (OR=2.18, 95% CI=1.84-2.59), planting mushroom and flowers (OR=1.46 and 1.53, 95% CI=1.13-1.87 and 1.24-1.95), and living in mountain and coastal region (OR=1.68 and 1.35, 95% CI=1.37-2.06 and 1.10-1.65) were associated with the development of COPD among greenhouse farmers. CONCLUSION: In northeast China, COPD is highly prevalent among greenhouse farmers, and advanced age, smoking, planting mushroom, and flowers, as well as living in mountain and coastal regions, are potential risk factors for this disease.

Enhanced Anti-Tumor (Anti-Proliferation) Activity of Recombinant Human Interleukin-29 (IL-29) Mutants Using Site-Directed Mutagenesis Method.

Interferon (IFN)-λ, also known as IL-28A, IL-28B, or IL-29, is a new type III IFN, which shares many functional characteristics with type I IFN (α/ß). Currently, IFN-α is used in the treatment of certain forms of cancer with severe adverse effects. Some researches had stated that IFN-λs induced a similar but restricted growth inhibition of tumor cells relative to IFN-α; moreover, mutations of IFN-λs could strongly impact its biological properties. In this study, three hIL-29 mutants (K33R, R35K, and K33R/R35K) were generated by site-directed mutagenesis and efficiently expressed in Pichia pastoris GS115, which have considerable abilities to inhibit the growth of BEL-7402, HCT-8, and SGC-7901 tumor cells in vitro. The results showed that these mutants (K33R, R35K, and K33R/R35K) exhibited a significantly enhanced anti-proliferation activity against these tumor cells, compared with native hIL-29 in vitro. Further assay in vitro indicated that superior to K33R and R35K, K33R/R35K had a significant increase in anti-tumor activity compared with IFN-α2b, which suggested that the K33R/R35K could make improvement for the effectiveness of native hIL-29 in clinic and could be used as a potentially powerful candidate for cancer immunotherapy.

Association between the ABCA1-565C/T gene promoter polymorphism and coronary heart disease severity and cholesterol efflux in the Chinese Han population.

BACKGROUND: ABCA1 -565C/T gene promoter variants have been associated with the severity of coronary artery disease in Western populations. The purpose of our study was to investigate the association between the -565C/T gene polymorphism and coronary artery disease severity and cholesterol efflux in the Chinese Han population. METHODS: A cohort of 298 acute coronary syndrome (ACS) patients and 541 healthy controls was genotyped using the highly sensitive ligase detection reaction. ABCA1 -565C/T genotype was correlated with the clinical features of 164 acute myocardial infarction (AMI) patients. Monocytes from patients with various -565C/T gene polymorphisms were isolated and differentiated into foam cells by coincubation with [(3)H]-labeled acetyl-low-density lipoprotein cholesterol. ABCA1 mRNA and protein expression levels were evaluated, as well as cellular cholesterol efflux. RESULTS: The frequency of the TT genotype in the -565C/T polymorphism of ACS patients was significantly increased when compared with controls (0.211 vs. 0.162, p<0.05). The TT genotype, but not the CT or CC genotypes, in the -565C/T gene polymorphism correlated with the severity of the coronary lesion observed in AMI patients. Patients with the TT homozygote genotype also exhibited significantly lower cellular cholesterol efflux (TT [6.37%±0.554%]) levels than controls and also had the lowest levels of ABCA1 mRNA and protein expression among the group of variants. In contrast, cholesterol efflux levels in AMI patients with CT [11.35%±3.975%] and CC ([15.32%±6.293%]) genotypes were not significantly different from controls. CONCLUSIONS: Impaired ABCA1-mediated cholesterol efflux in macrophages may be associated with the severity of the coronary lesions in AMI patients with the TT genotype at the -565C/T gene polymorphism.

[Risk factors on chronic obstructive pulmonary disease among greenhouse workers in Liaoning province].

OBJECTIVE: To study the risk factors of chronic obstructive pulmonary disease (COPD) among greenhouse farmers in Liaoning province. METHODS: According to geographical differences in Liaoning province, stratified-cluster-random sampling method was used. A total of 5420 greenhouse farmers working in more than 800 greenhouses were investigated with unified questionnaire, physical examination, blood routine examination, blood gas analysis, chest X-ray and pulmonary function tests. Diagnosis of COPD was made according to the criteria for "chronic obstructive pulmonary disease of diagnosis and treatment guidelines" (2007 revision) by the Chinese Respiratory Disease Society. RESULTS: The total number of farmers under study was 5880, including 5420 respondants (92.18%) with effective data. Risk factors were found on age (χ2=32.530, P=0.000), time working in greenhouses every day (χ2=21.311, P=0.000), frequency of ventilation (χ2=9.791, P=0.007) and the location of the greenhouses (χ2=73.645, P=0.000). When using SPSS 17.0 for the single factor logistic regression analysis, results indicated that smoking (OR=1.976, 95%CI: 1.672 - 2.334), age (OR=4.188, 95%CI: 3.718-4.718), greenhouses for fungus (compared with vegetables, OR=1.302, 95%CI: 1.016-1.669), flowers and plants (compared with vegetables greenhouses, OR=1.503, 95%CI: 1.201-1.880) were the risk factors of COPD among greenhouse farmers while the protective factor was the years of working in the greenhouse (OR=0.684, 95%CI: 0.609-0.767). CONCLUSION: The overall morbidity of COPD among greenhouse farmers in Liaoning province was 17.47% with various risk factors.

Association between lipoprotein-associated phospholipase A2 gene polymorphism and coronary artery disease in the Chinese Han population.

The role of the lipoprotein-associated phospholipase A(2) gene (PLA2G7) in atherosclerosis remains controversial. We investigated the frequency of single-nucleotide polymorphisms (SNPs) of PLA2G7 (rs16874954 and rs1051931) and their association with coronary artery disease (CAD) in a cohort of CAD patients (n= 806) and age-matched healthy controls (n= 482) in the Chinese Han population. The VF and FF genotype of rs16874954 was significantly more frequent in the CAD patients (13.5%) than in the controls (9.3%, P= 0.024). The association remained after adjustment for age, gender, body mass index, smoking status, history of diabetes, positive family history of CAD, high-density lipoprotein cholesterol, and triglyceride (OR = 1.922; 95% CI [1.146-3.224]; P= 0.013). There was no significant difference in the frequency of any genotype of rs1051931 between the two groups. However, the frequency of the allele V379 was significantly greater in CAD patients with a history of myocardial infarction (MI) than in those without a history of MI (18.7% and 14.8%, P= 0.038). We conclude that there is significant association between the rs16874954 mutation and CAD in the Chinese Han population. The expression of rs1051931 variant in CAD patients may entail increased risk of MI.

A polymorphism in the ABCG1 promoter is functionally associated with coronary artery disease in a Chinese Han population.

OBJECTIVE: In this study, we examine the association of single nucleotide polymorphisms (SNPs) of the human ATP binding cassette transporter G1 (ABCG1) gene with atherosclerotic coronary artery disease (CAD) in a Chinese Han population. METHODS: 1021 patients with CAD and 1013 unaffected control subjects were enrolled. PCR-based ligation detection reaction (PCR-LDR) method was used to genotype four SNPs of ABCG1, three (rs2234714, rs2234715 and rs57137919) in the promoter region and one (rs1044317) in the 3'-untranslated region (UTR). RESULTS: The human ABCG1 -367G>A polymorphism (rs57137919) showed a significantly decreased risk for CAD and myocardial infarction (MI) in a dominant model (adjusted OR = 0.73, p = 0.033 for CAD, and adjusted OR = 0.65, p = 0.014 for MI, respectively). The rs57137919 also showed an association with angiographic severity of CAD (multi-vessel vs. single-vessel CAD, adjusted OR = 0.40, p = 0.005). The findings were further supported by luciferase reporter assay, in which the polymorphism impaired reporter gene expression. The ABCG1 -768G>A polymorphism (rs2234714) showed an association with CAD in a recessive model (adjusted OR = 0.64, p = 0.015), but did not demonstrate a functional influence on reporter gene expression in the luciferase reporter assay. CONCLUSIONS: The SNP rs57137919 in the ABCG1 promoter region is functionally associated with a reduced risk of CAD in a Chinese Han population.

[Screening of three novel antimicrobial peptides with antifungal pathogens].

OBJECTIVE: In order to discover novel antimicrobial peptides against important crop pathogens, we designed and screened a high capacity random peptide library and isolated a number of clones expressing peptides with antifungal activity. We selected 96 peptides from the library and synthesized their sequence, which were used to assay their activity against crop fungal pathogens. METHODS: Using agar diffusion assay, these peptides were assayed for their activity against pathogens that cause cotton Fusarium wilt (Fusarium f. sp, vasinfecum), cotton red rot (Fusarium moniliforme), wheat spot blotch (Bipolaris sorokiniana) and potato early blight (Alternaria solani). RESULTS: The three random peptides, A6, D4 and F10, showed the strongest activity against the above four crop fungal pathogens. Through Blastp analysis, we did not find they have homologous sequences with known antimicrobial peptides. CONCLUSION: The novel antimicrobial peptides will provide gene resources for preventing important crop pathogens.

Polyaspartamide gadolinium complexes containing sulfadiazine groups as potential macromolecular MRI contrast agents.

Both diethylenetriaminepentaacetic acid (DTPA) and sulfadiazine (SD) were incorporated into polyaspartamides with different side chains, including poly-alpha,beta-[N-(2-hydroxyethyl)-L-aspartamide] (PHEA), poly-alpha,beta-[N- (3-hydroxypropyl)-L-aspartamide] (PHPA), poly-alpha,beta-[N-(2-aminoethy1)-L-aspartamide] (PAEA), poly-alpha,beta-[N-(4-aminobuty1)-L-aspartamide] (PABA), and poly-alpha,beta-[N-(6-aminohexyl)-L-aspartamide] (PAHA). The polyaspartamide ligands containing DTPA and SD groups were further reacted with gadolinium chloride to give the corresponding macromolecular gadolinium complexes. Experimental data of 1H NMR, IR, UV, and elemental analysis exhibited the formation of the polyaspartamide ligands and gadolinium complexes. Relaxivity studies indicated that the macromolecular chelates possess higher relaxivities than that of the clinically used Gd-DTPA. MR imaging showed that the macromolecular chelate PAEA-Gd-DTPA-SD greatly enhanced the contrast of MR images of hepatoma in the lower limb of mice and provided prolonged intravascular duration. Thus the polyaspartamide gadolinium complex containing SD groups is expected to be used as the potential macromolecular MRI contrast agents for hepatoma in mice.