Assessment of toxic mechanisms and mode of action to three different levels of species for 14 antibiotics based on interspecies correlation, excess toxicity, and QSAR.

Antibiotics have received much attention owing to their ecotoxicity toward nontarget aquatic creatures. However, the mode of action (MOA) of toxicity against nontarget organisms is unclear in some aquatic organisms. In this study, the comparison of toxicities through interspecies correlations, excess toxicity calculated from toxicity ratio, and quantitative structure-activity relationship (QSAR) was carried out to investigate the MOAs for 14 antibiotics among Daphnia magna, Vibrio fischeri, and Pseudokirchneriella subcapitata. The results showed that interspecies toxicity correlations were very poor between any two of the three species for the 14 antibiotics. The toxicity ratio revealed that most antibiotics exhibited excess toxicity to algae and Daphnia magna but not to V. fischeri, demonstrating that some antibiotics share the same MOA, but some antibiotics share different MOAs among the three different levels of species. P. subcapitata was the most sensitive species, and V. fischeri was the least sensitive species. This is because of the differences in the biouptake and interactions of antibiotics with the target receptors between the three different trophic levels of the species. Molecular docking simulations suggested that the toxicity of antibiotics depends highly on their interactions with target receptors through hydrogen bonds, electrostatic or polar interactions, π bond interactions, and van der Waals forces. QSAR models demonstrated that hydrogen bonding and electrophilicity/nucleophilicity play key roles in the interaction of antibiotics with different receptors in the three species. The toxic mechanisms of antibiotics are attributed to the interactions between electrophilic antibiotics and biological nucleophiles, and hydrogen-bond interactions. These results are valuable for understanding the toxic mechanisms and MOA of the three different levels of species.

[Construction and application of comprehensive system of chronic diseases surveillance in Zhejiang province].

To construct a non-communicable disease system recommended by WHO, develop the key techniques and promote their applications, obtain the main health indicators and understand the prevalence of chronic diseases, and provide support for the prevention, control and research of chronic diseases. Based on factor analysis, K-means clustering and multi-cluster random sampling, 30 typical sampling areas at provincial level were designed and constructed; By referring to WHO's Non-communicable Disease Surveillance Framework and the American behavioral risk factor sampling and questionnaire and combined with China's actual needs, a comprehensive surveillance system for chronic diseases, covering morbidity and mortality, risk factor exposure and community management and control of chronic diseases, was established, a "5+12+1" quality control system for surveillance data collection, management, analysis and feedback was formed and a three-level surveillance information management platform and information technology construction standards in the province were established, resulting the integration of life registration, chronic disease case reporting and community chronic disease management. Using these key techniques, we have obtained high-quality surveillance data of the whole province, produced the main health indicators, carried out research of chronic diseases, and analyze the prevalence and changing trend of the main chronic diseases and related risk factors to boost the government's practical projects for the reform of the people's livelihood and facilitate the construction of "Healthy Zhejiang". The successful experiences and key techniques have been applied in the construction of chronic disease surveillance system in some provinces in China.

A synopsis of global frontiers in fertility preservation.

Since 2007, the Oncofertility Consortium Annual Conference has brought together a diverse network of individuals from a wide range of backgrounds and professional levels to disseminate emerging basic and clinical research findings in fertility preservation. This network also developed enduring educational materials to accelerate the pace and quality of field-wide scientific communication. Between 2007 and 2019, the Oncofertility Consortium Annual Conference was held as an in-person event in Chicago, IL. The conference attracted approximately 250 attendees each year representing 20 countries around the world. In 2020, however, the COVID-19 pandemic disrupted this paradigm and precluded an in-person meeting. Nevertheless, there remained an undeniable demand for the oncofertility community to convene. To maintain the momentum of the field, the Oncofertility Consortium hosted a day-long virtual meeting on March 5, 2021, with the theme of "Oncofertility Around the Globe" to highlight the diversity of clinical care and translational research that is ongoing around the world in this discipline. This virtual meeting was hosted using the vFairs ® conference platform and allowed over 700 people to participate, many of whom were first-time conference attendees. The agenda featured concurrent sessions from presenters in six continents which provided attendees a complete overview of the field and furthered our mission to create a global community of oncofertility practice. This paper provides a synopsis of talks delivered at this event and highlights the new advances and frontiers in the fields of oncofertility and fertility preservation around the globe from clinical practice and patient-centered efforts to translational research.

The Prevalence and Progression of Myopia in Elementary School Students in Shanxi Province, China During the COVID-19 Pandemic.

PURPOSE: To investigate the prevalence of myopia and the risk factors associated with its progression in elementary school students during the COVID-19 pandemic in Shanxi Province, China. METHODS: The investigation included 960 students spanning first to sixth grade from six elementary schools in Shanxi Province, China. All participants received non-cycloplegic refraction and vision tests in December of 2019 (before the COVID-19 pandemic) and in June of 2020 (after classes resumed). Information concerning the students' eye-use behaviors, physical activities, diet and sleep during the pandemic was collected using a questionnaire survey. A total of 913 students (457 males) completed all tests and the questionnaire. RESULTS: The overall prevalence rate of myopia was 16.6% in December of 2019, and it increased with age. There was no gender difference in the prevalence of myopia (χ2 = 3.210, P = .073), but females exhibited a lower average spherical equivalent (SE) (P = .026). When the classes were resumed 6 months later, the overall prevalence rate of myopia was found to be 39.4%, which was significantly higher than it before the pandemic (χ2 = 117.425, P < .001). The average SE of the participants was -0.95D, which was significantly lower than the average SE (-0.43D) before the pandemic (P < .001). SE variation (ΔSE) in grade 6 was significantly higher than that in grade 1. No significant difference in ΔSE was found between males and females. Analyses of ordinary least squares (OLS)-estimated linear, natural logarithmic and quadratic functions revealed that the progression of myopia during the COVID-19 pandemic was significantly correlated with screen time, types of electronic devices, the amount of sleep, age, and the number of parents with myopia. CONCLUSIONS: The prevalence rate and progression of myopia among elementary school students in Shanxi Province increased significantly during the COVID-19 pandemic, which was likely related to China's home-based online learning programs. Therefore, it is necessary to optimize the educational programs for elementary school students when they study at home. We recommend increased time for outdoor activities and limiting screen time.

[Neurofibromatosis type 1 initially presented with glaucoma in the Department of Ophthalmology: a case report].

An eleven-year-old boy visited the Department of Ophthalmology due to visual acuity loss accompanied by high intraocular tension in the left eye for one year. Besides glaucoma, the typical ocular manifestations of neurofibromatosis type 1 such as bilateral Lisch nodules of the iris, multiple patchy choroidal nodules and retinal microvascular abnormalities were identified, and Cafe-au-lait macules appeared on the body skin. Based on the medical history, clinical presentation and auxiliary examination results, the diagnosis of neurofibromatosis type 1 with secondary glaucoma in the left eye was confirmed.

Blood Flow Dynamics in a Giant Left Atrial Appendage Aneurysm Visualized by 4D-Flow CMR.

Aneurysms of the left atrial appendage (LAA) are rare entities that often require surgical intervention. We demonstrate multimodality imaging features of a giant LAA aneurysm, with a focus on 3-dimensional blood flow dynamics by using 4-dimensional-flow cardiac magnetic resonance. (Level of Difficulty: Advanced.).

[Analysis of correlation of community management index of essential hypertension and type 2 diabetes with probability of premature mortality caused by major non-communicable diseases in Zhejiang Province].

Objective: To evaluate the correlation of community management index of essential hypertension and type 2 diabetes with the probability of premature mortality of major chronic diseases. Methods: From 2016 to 2018, the management of essential hypertension and type 2 diabetes were obtained from annual report of comprehensive prevention and control of chronic diseases in communities of Zhejiang province. The death data of chronic diseases were obtained from Information Management System of Chronic Diseases of Zhejiang province and annual population data were obtained from Public Security Bureau of Zhejiang Province. The management of essential hypertension and type 2 diabetes in communities of Zhejiang Province from 2016 to 2018 was described. The death status of major chronic diseases, including cardiovascular diseases, malignant tumors, diabetes and chronic respiratory diseases, in the same period was also described. Spearman correlation analysis and linear regression model were used to explore the correlation of community management of essential hypertension and type 2 diabetes with the probability of premature mortality of major chronic diseases. Results: The number of essential hypertension patients under standardized management, blood pressure control and regular medication increased from 3.127 3, 2.811 5 and 3.569 7 million in 2016 to 3.355 9, 3.151 8 and 4.010 6 million in 2018, respectively. The number of type 2 diabetes patients with standardized management, blood glucose control and regular medication increased from 0.805 5, 0.687 5 and 0.913 4 million in 2016 to 0.912 6, 0.798 7 and 1.064 8 million in 2018, respectively. The standardized mortality rate of chronic diseases decreased from 403.07/100 000 in 2016 to 380.07/100 000 in 2018. The proportion of premature deaths of chronic diseases decreased from 28.39% in 2016 to 26.90% in 2018. The proportion of deaths from major chronic diseases in all chronic diseases decreased from 90.96% in 2016 to 90.69% in 2018.The probability of premature mortality decreased from 10.68% in 2016 to 9.67% in 2018. The spearman correlation analysis showed that the blood pressure control and regular drug use were negatively correlated with the probability of premature death of major chronic diseases (r values were -0.367 and -0.392; P values were 0.035 and 0.024). According to the linear regression model analysis, with increase of 100 000 of essential hypertension control cases or regular medication use cases of type 2 diabetes, the probability of premature death of major chronic diseases decreased by 0.47% (95%CI: 0.39%, 0.54%) or 1.31% (95%CI: 1.12%, 1.50%), respectively. Conclusion: From 2016 to 2018, the community management of essential hypertension and type 2 diabetes was negatively correlated with probability of premature death of major chronic diseases in Zhejiang province.

Case Report: Thromboembolism and Hemorrhagic Pericardial Effusion-The Janus Face of Primary Pericardial Angiosarcoma.

Background: Primary cardiac angiosarcomas, especially those originating in the pericardium, are extremely rare and aggressive tumors with poor prognosis. These types of malignant tumors have diverse clinical presentations and are often masked by other comorbidities. Case Summary: Our hospital reported a 59-year-old woman who initially presented with pulmonary thromboembolism (PTE) and was subsequently treated with low-molecular-weight heparin. However, she experienced acute pericardial tamponade after anticoagulation therapy, where no obvious mass was primarily identified upon imaging, both in the pericardium or within the heart. Emergency pericardiocentesis and drainage were performed, where a total of 210 mL of bloody effusion was drained. Four months later, she was hospitalized with progressive hemoptysis and dyspnea. A large mixed mass occupying the right pericardium was later identified by coronary computed tomography angiography (CCTA). The mass was consistent with the right atrium, with heterogeneous thickened pericardium and localized moderate pericardial effusion. CCTA and positron emission tomography scans later showed metastases in both lungs and bilateral pleura. Nodules in hilar and mediastinal lymph nodes were also significant. Ultrasound-guided biopsy was performed, and the patient was ultimately diagnosed with an angiosarcoma based on final positive results for both CD31 and CD34 markers. The patient refused chemotherapy and passed away while waiting for her pathology results. The patient survived for 6 months since the first reported episode of PTE. Conclusions: Our case indicates that patients presenting with both embolism and hemorrhage should urgently be channeled to a clinical specialist to confirm any malignant etiology. This would be beneficial to confirm an early diagnosis and lengthen the duration of patient survival. However, the diagnosis of primary cardiac angiosarcoma is still challenging and requires multiple imaging modalities and biopsies in order to assist the accurate diagnosis of disease and achieve effective patient management.

Role of miR-16-5p in the proliferation and metastasis of hepatocellular carcinoma.

OBJECTIVE: The aim of this study was to investigate the role of miR-16-5p in hepatocellular carcinoma (HCC), and to explore the possible underlying mechanism. PATIENTS AND METHODS: 100 pairs of cancerous and para-cancerous tissues surgically removed in our hospital were collected. Real Time quantitative-Polymerase Chain Reaction (qRT-PCR) was used to detect the expression level of miR-16-5p in tissues. Bioinformatics and Dual-Luciferase reporter gene assay were used to screen and verify the potential target genes of miR-16-5p, respectively. Human HCC SMMC-7721 cells were used for functional experiments. Cell proliferation was detected by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. Cell invasion and migration were evaluated by transwell and scratch wound-healing assay, respectively. The protein expression levels of epithelial-mesenchymal transition (EMT) associated markers were measured by Western blot (WB) assay. RESULTS: QRT-PCR showed that miR-16-5p expression in HCC tissues was significantly lower than that of adjacent normal liver tissues. At the cellular level, miR-16-5p was lowly expressed in HCC cells (SMMC-7721). Bioinformatics websites (including Targetscan, PicTar, miRanda) predicted that insulin-like growth factor 1 receptor (IGF1R) was a potential target gene of miR-16-5p. Meanwhile, IGF1R was selected for further investigation due to its metastatic function. The results showed that no significant difference was found in the mRNA expression level of IGF1R in HCC tissues. However, the protein level of IGF1R was significantly up-regulated, which was negatively correlated with miR-16-5p. Combined with Dual-Luciferase reporter gene assay, it was confirmed that miR-16-5p could regulate the expression of IGF1R in a targeted manner. Furthermore, down-regulation of IGF1R significantly reduced the inhibitory effect of miR-16-5p on the proliferation and metastasis of SMMC-7721 cells. CONCLUSIONS: We showed that miR-16-5p suppressed invasion and migration of HCC cells, mechanically by directly targeting and inhibiting IGF1R protein expression. The newly identified miR-16-5p/IGF1R axis might provide new insights into the pathogenesis of HCC and novel potential therapeutic targets for the treatment of HCC.

iTRAQ-based proteomic analysis of DMH-induced colorectal cancer in mice reveals the expressions of ß-catenin, decorin, septin-7, and S100A10 expression in 53 cases of human hereditary polyposis colorectal cancer.

PURPOSE: The aim of this study is to explore the roles of ß-catenin, decorin, septin-7, and S100A10 expression in colorectal cancer development. METHODS: Twenty-five BALB/c mice were divided into five groups; four groups were administrated N,N-dimethylhydrazine for 0, 10, 15, and 20 weeks, and one group was administrated normal saline for 20 weeks. The colons were collected for histopathological analysis. Protein samples prepared from the frozen colon tissues of mice treated with N,N-dimethylhydrazine for the different time points were evaluated using the isobaric tags for relative and absolute quantification (iTRAQ) labeling technique coupled with the 2D liquid chromatography-tandem mass spectrometry analysis. Based on the proteomic analysis results, immunohistochemical staining of ß-catenin, decorin, septin-7, and S100A10 was performed in paraffin-embedded mice colorectal tissue, and 53 cases of human hereditary polyposis colorectal cancer samples. RESULTS: Colorectal cancer was observed in mice treated with N,N-dimethylhydrazine for 20 weeks, and adenomas were observed in mice subjected to the 10-, and 15-week treatments. Seventy-two differentially expressed proteins were involved in the development of cancer as per the iTRAQ and spectrometry analysis. In normal epithelium, adenoma, and cancer from human hereditary polyposis colorectal cancer, S100A10 expression (c2 = 100.989, P = 0.000) was highest in cancer, whereas decorin (c2 = 12.852, P = 0.002) and septin-7 (c2 = 66.519, P = 0.002) expressions were highest in the normal epithelium, which was confirmed via immunohistochemical staining. CONCLUSIONS: The subcellular localization of ß-catenin and decorin, septin-7, and S100A10 expressions are associated with the development of colorectal cancer in mice after N,N-dimethylhydrazine treatment and in human hereditary polyposis colorectal cancers.

[Estimation on the health life expectancy of adults in Zhejiang province, 2016].

Objective: To estimate the health-adjusted life expectancy (HALE) of adults in Zhejiang province and evaluate the health status of the adults. Methods: This study was based on the mortality data collected from Zhejiang Chronic Disease Surveillance Information and Management System, and mortality rates from the underreporting survey and self-reported health data in 2016. Hierarchical Ordered Probit (HOPIT) model was used to estimate the severity-weighted prevalence of disability. Sullivan's method was used to calculate the HALE. Results: After adjustment by HOPIT model, the severity-weighted prevalence of disability increased significantly with age (χ(2)=5 795.81,P<0.001), and it was higher in females than in males (χ(2)=5 353.27, P<0.001). The life expectancy and self-evaluated HALE were 59.08 years and 48.68 years, respectively, in those aged ≥20 years, the difference was 10.40 years due to disability. The proportion of HALE loss due to disability in the total life expectancy was 17.61%, and it increased with age. HALE was higher in males than in females (49.21 years vs. 48.14 years), and in urban residents than in rural residents (49.92 years vs. 47.43 years). Conclusion: The proportion of loss of HALE in the total life expectancy in adults was high in Zhejiang, and it higher in males than in females, in urban residents than rural residents. Programs on improving health care in women and rural residents should be promoted.

[Study on the Specific Complexation of GMDTC and Metal Ion].

Objective: Study the response of GMDTC to cadmium ions and metal ions in vivo to determine whether GMDTC are specifically complexed with cadmium ions to provide a reference for the safety and dfficacy of GMDTC. Methods: Complexometric titration, HPLC and HPLC-MS were applied to research the complexation reaction of GMDTC and various metal ions. The molecular ion peak of GMDTC, GMDTC-Cd complex and GMDTC-Pb complex also detected by LC-MS. Additionally, the initial structure was determined by DFT simulation method. Results: Results of complexometric titration and HPLC detection showed that GMDTC characteristic absorption peak area was proportional to the concentration of itself and there was no color change and peak time change when the GMDTC mixed with Ca(2+), Fe(2+), Mg(2+), Zn(2+). However, the color changed to black transition when the GMDTC mixed with Cu(2+) and the color changed from yellow precipitate to light yellow transparent transition when GMDTC mix with Hg(2+). Moreover, the peak area as well as the retention time has changed a lot which indicated that a chemical reaction has already happened. When the GMDTC mixed with Cd(2+) and Pb(2+), the color has changed from pale yellow to colorless transparent and the peak area of GMDTC has increased a lot. Finally, the GMDTC-Cd complex ratio both of which are 2:1 were calculated based on the results of LC-MS instrument and atomic calculations. Conclusion: The specific cadmium chelating agent GMDTC can not react with the Ca(2+), Fe(2+), Mg(2+), Zn(2+), but it can react chemically with Cu(2+) and Hg(2+), even specific complex with Pb(2+) and Cd(2+).

[Impact of diabetes prevalence and mortality on health life expectancy among residents in Zhejiang province].

Objective: To evaluate the impact of diabetes prevalence and mortality on health life expectancy (HLE). Methods: A cause-excluded health adjusted life expectancy method was used to quantitatively analyze the impact of diabetes on HLE and the composition of health life losses (HLL), using the integrated data on population mortality, self-assessed health status and diabetes prevalence. Results: The HLE for people aged 15 was 55.80 in Zhejiang, in 2013. After removing the diabetes morbidity and mortality, the HLE for men aged 15 increased by 0.86 and 1.13, respectively, with an increase of 1.04 and 0.66 for urban and rural residents. Substantial increase of HLE was observed in women and urban residents than those for men and rural residents. HLL caused by diabetes mortality and morbidity appeared as 0.10 and 0.79, with a ratio of 7.92. Conclusion: HLL caused by diabetes mortality was much greater than those caused by diabetes mortality, suggesting the most effective measure in reducing the diabetes-related HLL is to promote the healthy lifestyle in urban areas and especially for women.

[Morbidity and mortality of malignant tumor in Zhejiang province, 2014].

OBJECTIVE: To analyze the morbidity and mortality of malignant tumor in Zhejiang province in 2014. METHODS: The data were collected from Zhejiang provincial chronic disease surveillance system in 2014. The crude rate, age-standardized rate, cumulative rate(0-74 years old), cut rate(35-64 years old), age-specific and area-specific morbidity/mortality as well as the constitution of top 10 leading cancers were then calculated and analyzed. The age-standardized rate was calculated according to the standard population in China in 1982 and the Segi' s world standard population. RESULTS: The crude morbidity was 348.80/100 000(370.74/100 000 in males and 326.51/100 000 in females). The age-standardized morbidity according to the standard population in China and according to world standard population were 168.84/100 000 and 217.23/100 000 respectively, the cumulative morbidity was 24.66% and the cut morbidity was 376.40/100 000. Age-specific morbidity in age group 0-34 years remained low; however, the morbidity increased obviously in age group ≥35 years, increased more rapidly in age group ≥50 years and finally reached the peak in age group 80-84 years(1 618.20/100 000). The morbidity of malignant tumor, age-standardized morbidity(China standard)and age-standardized morbidity(world standard)were 381.81/100 000, 185.15/100 000 and 236.27/100 000 respectively in urban area, and 330.23/100 000 , 159.47/100 000 and 206.29/100 000, respectively in rural area. The crude mortality was 189.08/100 000(248.57/100 000 in males, 128.72/100 000 in females), and the age-standardized mortality according to China population and world population were 97.56/100 000 and 135.54/100 000 respectively. The cumulative mortality was 15.08%, and the cut mortality was 162.75/100 000. Age-specific mortality increased in age group 45-49 years(92.29/1000 000)and reached the peak in age group ≥85 years(2 263.70/100 000). The mortality was higher in rural area(190.60/100 000)than in urban area(186.38/100 000). The leading cancers were lung cancer, colorectum cancer, thyroid cancer, stomach cancer and liver cancer, accounting for 58.64% of the total. Lung cancer, liver cancer, stomach cancer, colorectum cancer and esophagus cancer were the major cancers causing deaths, accounting for 70.72% of all the total. CONCLUSION: The leading cancers were lung cancer, colorectum cancer, thyroid cancer, stomach cancer and liver cancer in Zhejiang in 2014, close attention should be paid to thyroid cancer in women. The disease burden of malignant tumor is increasing,it is necessary for health department to take effective measures to reduce the disease burden caused by malignant tumor.

Rapidly rising incidence of Type 1 diabetes in children and adolescents aged 0-19 years in Zhejiang, China, 2007 to 2013.

AIMS: To investigate the incidence rates and trends in Type 1 diabetes in children and adolescents aged 0-19 years in the registered Zhejiang population over the period 2007-2013 by age, sex and calendar year. METHODS: In total, 611 individuals with newly diagnosed Type 1 diabetes were identified from 30 districts in Zhejiang province over the study period. Annual incidence and 95% confidence intervals (CI) by age group and sex were calculated per 100 000 person-years. Trends in diabetes incidence and the associations of age and sex with Type 1 diabetes were assessed using Poisson regression models. RESULTS: The mean annual age-standardized incidence of diabetes was 2.02/100 000 person-years (95% CI: 1.92-2.12), with an average annual increase of 12.0% (95% CI: 7.6-16.6%) over the study period. The risk for Type 1 diabetes in girls was estimated to be 1.25 (95% CI: 1.07-1.47) times higher than that in boys. Compared with those aged 0-4 years, the 5-9, 10-14 and 15-19 years age groups were at significantly greater risk, with adjusting incidence rate ratios of 3.54, 6.58 and 5.39, respectively. The mean age at diagnosis decreased significantly from 12.85 years in 2007 to 11.21 years in 2013. A steep rise in diabetes incidence was observed in the under 5 years age group, which showed the greatest increase at 33.61%. CONCLUSIONS: The incidence of diabetes in Zhejiang was relatively low, although rapidly rising trends have been found in recent years, particularly in younger children. Further monitoring and research are urgently required to better understand possible environmental risk factors and formulate preventive strategies.

Common variant rs7597774 in ADD2 is associated with dilated cardiomyopathy in Chinese Han population.

Two polymorphisms, rs7597774 and rs1739843 in ADD2 and HSPB7 respectively, were found to be associated with dilated cardiomyopathy (DCM) in European cohorts but the results were not validated in the Chinese Han population. We aimed to test the association of the two variants with DCM in a cohort of Chinese Han population. DCM (399) and control (1384) individuals were identified from the GeneID database in China, and DNA was isolated from peripheral blood lymphocytes for genotyping. Alleles were amplified by PCR, and amplicons harboring polymorphisms rs1739843 and rs7597774 were directly genotyped using high-resolution melting analysis. Statistical analysis was subsequently performed to evaluate the association of the variants with DCM. Allelic analysis demonstrated that rs7597774 was significantly related to DCM (P -adj = 0.0157), and an increased risk of DCM was specifically associated with the minor allele A (OR = 1.582). High-grade cardiac dysfunction (NYHA III/IV) was a clinical parameter significantly associated with the rs7597774 genotypes AA + AC relative to genotype CC (P = 0.021). Furthermore, DCM patients with the rs7597774 genotype AA tended to undergo more invasive medical interventions than those with the genotype CC (P = 0.008). No association was detected between rs1739843 and DCM under any allelic (P -adj = 0.407, OR = 0.920) or genotypic model. In the Chinese Han population, rs7597774 but not rs1739843 was found to be associated with DCM. This study is the first to demonstrate that underlying genotypes of rs7597774 may assist in assessing the heart functional status of DCM patients and also in the prediction of the benefit of particular therapies for these patients.

Tumour size is the only predictive factor of distant recurrence after pathological complete response to neoadjuvant chemotherapy in patients with large operable or locally advanced breast cancers: a sub-study of EORTC 10994/BIG 1-00 phase III trial.

PURPOSE: Although achieving a pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) in breast cancer predicts a better outcome, some patients still relapse. The objectives of this study were to describe the types of events in this group of patients and to identify predictive factors for relapse. METHODS: Patients with large operable or locally advanced breast cancers (T4d tumours were excluded) were randomised to receive either six cycles of anthracycline-based chemotherapy or three cycles of docetaxel followed by three cycles of eprirubicin/docetaxel. pCR was defined as no evidence of residual invasive cancer (or very few scattered tumour cells) in the primary tumour and axillary lymph nodes at surgery. Two Cox regression analyses were performed to identify predictive factors of relapse: one for recurrence-free interval (RFI) and one for distant recurrence-free interval (DRFI). RESULTS: Out of 283 eligible patients who achieved a pCR, 40 (14.1%) and 28 (9.9%) presented an event of interest for the RFI and DRFI analyses, respectively. Five-year RFI, DRFI and overall survival (OS) were 85.3% (95% confidence interval (CI), 80.1-89.3), 89.6% (95% CI, 85.0-92.9) and 91.9% (95% CI, 87.2-94.9), respectively. No predictors for RFI after pCR were identified. For DRFI, tumour size was the only predictor: Hazard ratio (HR) T3 versus T1-2=3.62 (95% CI, 1.66-7.89); HR T4 versus T1-2: HR, 2.80 (95% CI, 0.62-12.64) p=0.0048. CONCLUSION: In this study, clinical tumour size emerged as the only predictor for DRFI after pCR, with T3 and T4 tumours having an increased risk for distant recurrence compared to T1-2 tumours.

Cytotoxicity of CD56-positive lymphocytes against autologous B-cell precursor acute lymphoblastic leukemia cells.

Precursor B-lineage acute lymphoblastic leukemia (pre-B ALL) affects hematopoietic development and therefore is associated with immune deficiencies that can be further exacerbated by chemotherapy. It is unclear if and when monoclonal antibodies (mAbs) that stimulate antibody-mediated cellular cytotoxicity (ADCC) can be used for treatment because this depends on the presence of functional effector cells. Here, we used flow cytometry to determine that patient samples at diagnosis, post-induction and relapse contain detectable numbers of CD56+ cells. We were able to selectively expand CD56+ immune effector cells from bone marrow and peripheral blood samples at diagnosis and at various stages of treatment by co-culture with artificial antigen-presenting K562 clone 9.mbIL-21 cells. Amplified CD56+CD3- cells had spontaneous and anti-B cell-activating factor receptor mAb-stimulated ADCC activity against allogeneic ALL cells, which could be further enhanced by IL-15. Importantly, matched CD56+ effector cells also killed autologous ALL cells grown out from leukemia samples of the same patient, through both spontaneous as well as antibody-dependent cellular cytotoxicity. Since autologous cell therapy will not be complicated by graft-versus-host disease, our results show that expanded CD56+ cells could be applied for treatment of pre-B ALL without transplantation, or for purging of bone marrow in the setting of autologous bone marrow transplants.

Microbial response to repeated treatments of manure containing sulfadiazine and chlortetracycline in soil.

Substantive addition of antibiotic-contaminated manure to agricultural soil may lead to "persistent" residues of antibiotics and may affect soil health. Therefore, this study examines the effects of repeated manure treatments containing sulfadiazine (SDZ) and chlortetracycline (CTC) residues, both individually and combined, on the functional diversity and structure of soil microbial communities in the soils under laboratory conditions. The average well color development (AWCD), Simpson diversity index (1/D, dominant populations), Shannon-Wiener diversity index (H', richness), and McIntosh diversity index (U, evenness) in the antibiotics-treated soils decreased in the first 60-day treatment and then gradually recovered or even exceeded the initial level in the unamended soils with increasing treatment frequency. A total of 11 specific bands in temperature gradient gel electrophoresis (TGGE) profiles were observed and sequence analyzed for five repeated treatments, and most of them belonged to the phyla Firmicutes, Actinobacteria, and Proteobacteria. These results indicate that repeated treatments of manure containing SDZ and CTC residues can alter soil microbial community structure, although they have a temporary suppression effect on soil microbial functional diversity.