[Analysis of the status of excess heart age and its risk factors among residents aged 35 to 64 years in China].

Objective: To analyze the status of excess heart age and its risk factors among Chinese residents aged 35 to 64 years. Methods: The study subjects were Chinese residents aged 35 to 64 years who completed the heart age assessment by WeChat official account "Heart Strengthening Action" through the internet from January 2018 to April 2021. Information such as age, gender, body mass index (BMI), blood pressure, total cholesterol (TC), smoking history, and diabetes history was collected. The heart age and excess heart age were calculated according to the characteristics of individual cardiovascular risk factors and the heart aging was defined as excess heart age≥5 years and 10 years respectively. The heart age and standardization rate were calculated respectively based on the population standardization of the 7th census in 2021.CA trend test was used to analyze the changing trend of excess heart age rate and population attributable risk (PAR) was used to calculate the contribution of risk factors. Results: The mean age of 429 047 subjects was (49.25±8.66) years. The male accounted for 51.17% (219 558/429 047) and the excess heart age was 7.00 (0.00, 11.00) years. The excess heart age rate defined by excess heart age≥5 years and ≥10 years was 57.02% (the standardized rate was 56.83%) and 38.02% (the standardized rate was 37.88%) respectively. With the increase of the age and number of risk factors, the excess heart age rate of the two definitions showed an upward trend according to the result of the trend test analysis (P<0.001). The top two risk factors of the PAR for excess heart age were overweight or obese and smoking. Among them, the male was smoking and overweight or obese, while the female was overweight or obese and having hypercholesterolemia. Conclusion: The excess heart age rate is high in Chinese residents aged 35 to 64 years and the contribution of overweight or obese, smoking and having hypercholesterolemia ranks high.

[Mechanism of nerve growth factor promotes angiogenesis and skeletal muscle fiber remodeling in a mouse hindlimb ischemic model].

Objective: To explore the mechanism of nerve growth factor (NGF) in the skeletal muscle fiber remodeling in ischemic limbs during therapeutic angiogenesis. Methods: Eighteen female mice with SPF grade, 6 weeks old and 25-30 g weighed were randomly allocated to sham-operated group (n=6), blank control group (n=6) and NGF gene transfection group (n=6). The left hindlimb ischemia models were established by ligating the femoral artery in blank control group and NGF gene transfection group. Seven days after the operation, mice in the three groups were separately injected with normal saline, empty plasmids, and NGF plasmids. Gastrocnemius of left hindlimbs was harvested after the blood perfusion assessment of the ischemic limb on the 21st postoperative day. The gastrocnemius muscle specimens were stained with HE, CD31 and proliferating cell nuclear antigen (PCNA) immunohistochemistry staining, the mRNA expressions of myosin heavy chain-Ⅰ(MHC-Ⅰ), MHC-Ⅱa and MHC-Ⅱb were measured by real-time PCR, and the protein level of NGF and peroxisome proliferator-activated receptors-ß/δ (PPAR ß/δ) were detected by Western blot. The expression of cytochrome C oxidase (COX), isocitrate dehydrogenase (IDH) and adenosine triphosphate (ATP) were examined by enzyme-linked immunosorbent assay (ELISA). Results: On the 21st day after operation, the blood perfusion of the ischemic limb in NGF gene transfection group was (195.70±9.99)PU, which was lower than that in sham-operated group (312.15±17.32)PU (P=0.001), while it was higher than that in blank control group (82.11±8.55)PU (P=0.001). The degree of muscle atrophy in the NGF gene transfection group was lower than that in the blank control group. The capillary density of NGF gene transfection group (0.34±0.05) was higher than that of sham-operated group (0.11±0.03) and blank control group (0.27±0.04) (P<0.05). The endothelial cell proliferation index in NGF gene transfection group (0.39±0.19) was significantly higher than that in sham-operated group (0.18±0.01) and blank control group (0.25±0.14) (P<0.05). The expression of NGF, PPAR ß/δ, COX, IDH, ATP, and MHC-Ⅰ mRNA in NGF gene transfection group were significantly higher than those in sham-operated group and blank control group (P<0.05). Conclusions: NGF gene transfection can promote angiogenesis in the ischemic limbs of mice, increase the blood perfusion, and thus induce the remodeling of skeletal muscle fibers to type Ⅰ. This process may be related to NGF-induced PPAR ß/δ expression and promote the cellular aerobic metabolism in skeletal muscle.

Relationship Between Early Functional and Structural Brain Developments and Brain Injury in Preterm Infants.

BACKGROUND: Recent studies explored the relationship between early brain function and brain morphology, based on the hypothesis that increased brain activity can positively affect structural brain development and that excitatory neuronal activity stimulates myelination. OBJECTIVE: To investigate the relationship between maturational features from early and serial aEEGs after premature birth and MRI metrics characterizing structural brain development and injury, measured around 30weeks postmenstrual age (PMA) and at term. Moreover, we aimed to verify whether previously developed maturational EEG features are related with PMA. DESIGN/METHODS: One hundred six extremely preterm infants received bedside aEEGs during the first 72h and weekly until week 5. 3T-MRIs were performed at 30weeks PMA and at term. Specific features were extracted to assess EEG maturation: (1) the spectral content, (2) the continuity [percentage of spontaneous activity transients (SAT%) and the interburst interval (IBI)], and (3) the complexity. Automatic MRI segmentation to assess volumes and MRI score was performed. The relationship between the maturational EEG features and MRI measures was investigated. RESULTS: Both SAT% and EEG complexity were correlated with PMA. IBI was inversely associated with PMA. Complexity features had a positive correlation with the cerebellar size at 30weeks, while event-based measures were related to the cerebellar size at term. Cerebellar width, cortical grey matter, and total brain volume at term were inversely correlated with the relative power in the higher frequency bands. CONCLUSIONS: The continuity and complexity of the EEG steadily increase with increasing postnatal age. Increasing complexity and event-based features are associated with cerebellar size, a structure with enormous development during preterm life. Brain activity is important for later structural brain development.

Resveratrol induces proliferation in preosteoblast cell MC3T3-E1 via GATA-1 activating autophagy.

Resveratrol (RSV) could promote osteogenic activity, but its clinical application has been hampered in view of its poor bioavailability. Therefore, it is desirable to identify with certainty the molecular target of its bone mass boosting function, which is crucial to the design of an effective therapeutic strategy for the optimal treatment of osteoporosis. Emerging evidence has indicated that GATA-1, an important transcription factor in megakaryocyte and erythrocyte differentiation, can directly activate autophagy in erythrocytes, alluding to its impact on bone metabolism. In light of this, we sought to determine whether GATA-1 would be a putative target by which RSV would act on osteoblast proliferation and, if so, to explore the underlying mechanism involved in the process. We examined the cell viability, colony formation, cell cyclin expression, autophagy level, and the expression levels of GATA-1 and adenosine 5'-monophosphate (AMP)-activated protein kinase α (AMPKα) in osteoblastic cell strain MC3T3-E1. The results showed that RSV promoted the proliferation process in MC3T3-E1 coupled with increased expression of GATA-1 and phosphorylated AMPKα and activated autophagy. When GATA-1 was interfered with siRNA, both autophagy and proliferation were decreased. Administration of the agonist of phosphorylated AMPKα1 (Thr172) promoted the translocation of GATA-1 into the nucleus. Based on the above results, we concluded that RSV induces the proliferation of MC3T3-E1 by increasing GATA-1 expression, which thence activates autophagy; and of note, AMPKα is one of the upstream regulators of GATA-1.

Diagnostic potential of urinary monocyte chemoattractant protein-1 for Alzheimer's disease and amnestic mild cognitive impairment.

BACKGROUND AND PURPOSE: The chemokine monocyte chemoattractant protein-1 (MCP-1) is involved in the pathogenesis of Alzheimer's disease (AD). This study aimed to investigate whether urinary MCP-1 can distinguish patients with AD, patients with amnestic mild cognitive impairment (aMCI) and cognitively normal (CN) subjects. METHODS: A total of 754 participants, including 97 patients with AD, 50 patients with aMCI and 84 age- and sex-matched CN controls as well as a cohort of 523 CN subjects of different ages, were enrolled from five hospitals located in different areas of China. Urinary MCP-1 levels were determined using enzyme-linked immunosorbent assays. The correlations between urinary MCP-1 levels and cognition test scores or age were analysed. The optimal diagnostic sensitivity and specificity were determined using receiver operating characteristic curve analysis. RESULTS: In the cohort of CN subjects of different ages, urinary MCP-1 levels increased with ageing and were correlated with age. The urinary MCP-1 levels were higher in females than in males. In the cohort composed of patients with AD, aMCI and age- and sex-matched CN controls, urinary MCP-1 levels were significantly higher in patients with AD and aMCI than in CN controls. There were no differences in urine MCP-1 levels between the AD group and the aMCI group. The urinary MCP-1 levels were correlated with the Mini-Mental State Examination scores and age, and were able to differentiate patients with AD and aMCI from CN subjects. CONCLUSIONS: Urinary MCP-1 is a potential biomarker for the diagnosis of AD and aMCI.

[A prospective study of bone loss in early stage postmenopausal breast cancer treated with aromatase inhibitors].

Objective: To investigate the occurrence and development of aromatase inhibitors (AIs) related bone loss in Chinese patients with postmenopausal early-stage breast cancer. Methods: Patients with estrogen receptor (ER) and (or) progesterone receptor(PR) positive postmenopausal early-stage breast cancer who received Letrozole, Anastrozole, or Exemestane as adjuvant therapy were enrolled. Before treatment, baseline bone mineral density (BMD), bone metabolism markers were examined and a lifestyle questionnaire was completed; BMD was examined annually during the treatment; Outpatient visits were conducted to record recurrent and fatal events. Results: From November 2013 to August 2016, 131 patients with breast cancer eligible for enrollment were enrolled. A total of 65 patients had normal baseline bone mass, and 68 patients had reduced bone mass. Letrozole was taken in 69 patients, anastrozole in 52 patients, and exemestane in 10 patients. With a median follow-up of 43.7 months, 100 patients could be evaluated for changes in bone mineral density. Bone mineral density of femoral neck, total hip, and lumbar spine L1 to 4 decreased year by year, and the decrease was the most significant in the first year, which decreased by 2.3%, 2.4%, and 3.9% respectively. Ten new cases of osteoporosis occurred in two years, eight of them occurred in the lumbar spine, all of whom had reduced bone mass at baseline. Among the 131 patients who completed the lifestyle questionnaire, the proportions of daily calcium supplementation and vitamin D were 28.2% and 7.6%, respectively; more than half (52.7%) of them lacked regular exercise. Conclusion: BMD was declining steadily in patients treated with AIs, especially in the first year. Lumbar spine is the most common osteoporosis site, early prevention and health education should be strengthened.

[Comparison the efficacy and prognosis of different first-line treatment for elderly diffuse large B-cell lymphoma].

Objective: To investigate the clinical features, survival and prognostic factors of elder patients with diffuse large B-cell lymphoma (DLBCL). Methods: The clinical data of elder patients with diffuse large B-cell lymphoma enrolled in the Cancer Hospital of Chinese Academy of Medical Sciences from April 2006 to December 2012 were retrospectively collected. All the patients were divided into R-CHOP-like group and CHOP-like group according to the dosage regimen. And the differences in demographic characteristics, clinical features, survival time and prognostic factors were compared between these two groups. Results: A total of 158 patients were enrolled, of which 78 patients in the R-CHOP-like group and 80 patients in the CHOP-like group were eligible. There were no significant differences between two groups on age, gender, pathological staging, B symptoms, bulky mass, ECOG score, IPI score, pathological type, LDH level, ß(2)-MG level, lymphocyte/monocyte ratio(LMR), neutrophils/lymphocyte ratio(NLR), platelet/lymphocyte ratio(PLR), Ki-67 index and bone marrow invasion. In the R-CHOP like group, the median progression-free survival (PFS) time was 10 months, and the median overall survival (OS) time was 30 months. The 1-year and 2-year PFS rates were 46.2% and 19.2%, respectively. The 1-, 2-, and 5-year OS rates were 79.5%, 59.0%, and 19.2%, respectively. In the CHOP-like group, the median PFS was 7 months, and the median OS was 15 months. The 1-year and 2-year PFS rates were 27.5% and 12.5% respectively. The 1-year, 2-year, and 5-year OS rates were 65.0%, 32.5% and 13.8%, respectively. The median PFS time and OS time in the R-CHOP group were significantly better than those in the CHOP group (P<0.05 for both). A stratified analysis showed that the PFS time and OS time were superior in the R-CHOP-like group compared to the CHOP-like group among patients older than 70 years (P<0.05 for both). In patients with stage Ⅲ-Ⅳ, the PFS time and OS time in the R-CHOP-like group were also superior to CHOP-like group (P<0.05 for both). Univariate Cox regression analysis showed that IPI score, LDH value, ß(2)-MG value, ECOG score, LMR, and PLR had an significant effect on prognosis (P<0.05 for all). Multivariate Cox regression analysis showed that lymphocyte/monocyte ratio and platelet/lymphocyte ratio were independent prognostic factors for diffuse large B-cell lymphoma (P<0.05 for both). Conclusions: The R-CHOP-like chemotherapy regimen is superior to the CHOP-like regimen in the first-line treatment of patients with diffuse large B-cell lymphoma. ECOG score, LMR and PLR may be independent prognostic factors for diffuse large B-cell lymphoma. ECOG score, LMR and PLR are independent prognostic factors.

Longitudinal study of neonatal brain tissue volumes in preterm infants and their ability to predict neurodevelopmental outcome.

Premature birth has been associated with poor neurodevelopmental outcomes. However, the relation between such outcomes and brain growth in the neonatal period has not yet been fully elucidated. This study investigates longitudinal brain development between birth and term-equivalent age (TEA) by quantitative imaging in a cohort of premature infants born between 26 and 36 weeks gestational age (GA), to provide insight into the relation of brain growth with later neurodevelopmental outcomes. Longitudinal T2-weighted magnetic resonance images (MRI) of 84 prematurely born infants acquired shortly after birth and TEA were automatically segmented into cortical gray matter (CGM), unmyelinated white matter (UWM), subcortical gray matter (SGM), cerebellum (CB) and cerebrospinal fluid (CSF). General linear models and correlation analysis were used to study the relation between brain volumes and their growth, and perinatal variables. To investigate the ability of the brain volumes to predict children's neurodevelopmental outcome at 18-24 months and at 5 years of age, a linear discriminant analysis classifier was tested and several general linear models were fitted and compared by statistical tests. From birth to TEA, relative volumes of CGM, CB and CSF with respect to total intracranial volume increased, while relative volumes of UWM and SGM decreased. The fastest growing tissues between birth and TEA were found to be the CB and the CGM. Lower GA at birth was associated with lower growth rates of CGM, CB and total tissue. Among perinatal factors, persistent ductus arteriosus was associated with lower SGM, CB and IC growth rates, while sepsis was associated with lower CSF and intracranial volume growth rates. Model comparisons showed that brain tissue volumes at birth and at TEA contributed to the prediction of motor outcomes at 18-24 months, while volumes at TEA and volume growth rates contributed to the prediction of cognitive scores at 5 years of age. The family socio-economic status (SES) was not correlated with brain volumes at birth or at TEA, but was strongly associated with the cognitive outcomes at 18-24 months and 5 years of age. This study provides information about brain growth between birth and TEA in premature children with no focal brain lesions, and investigates their association with subsequent neurodevelopmental outcome. Parental SES was found to be a major determinant of neurodevelopmental outcome, unrelated to brain growth. However, further research is necessary in order to fully explain the variability of neurodevelopmental outcomes in this population.

Anesthetic management of a patient with limb-girdle muscular dystrophy 2B:CARE-compliant case report and literature review.

BACKGROUND: Limb-girdle muscular dystrophies (LGMDs) belong to few neuromuscular disorders mainly involving pelvic and shoulder girdle muscles. Also, cardiac or pulmonary complications, increased rhabdomyolysis risk when exposed to volatile anesthetics and succinylcholine may increase anesthesia related risks. However, current reports about the anesthesia management of these patients are limited. CASE PRESENTATION: We described our anesthetic management of a 36 years old woman with LGMD 2B receiving arthroscopic knee surgery. In consideration of the high risk of rhabdomyolysis, total intravenous anesthesia (TIVA) was selected for her surgery. Considering the unpredictable respiratory depression, opioid based patient-controlled intravenous analgesia was replaced with an intra-articular cocktail therapy consisting of 20 ml of 0.2% ropivacaine. Also, we reviewed the literatures on anesthetic management of LGMD through searching PubMed, in order to provide a comprehensive and safe guidance for the surgery. CONCLUSIONS: Carefully conducted general anesthesia with TIVA technique is a good choice for LGMD patients. Neuraxial anesthesia may be used if general anesthesia needs to be avoided. To warrant safe anesthesia for surgery, any decision must be well thought out during perioperative period.

[Retrospective analysis of the clinical features and prognostic factors of 370 patients with advanced-stage diffuse large B-cell lymphoma].

Objective: The clinical features and prognosis of diffuse large B-cell lymphoma (DLBCL) were analyzed to optimize the treatment. Methods: We retrospectively collected the clinical data of patients with advanced-stage DLBCL from January 2006 to December 2012 in National Cancer Center/Cancer Hospital. The demographic characteristics, clinical stage, histological diagnosis, treatment and prognostic characteristics of these patients were analyzed. Results: A total of 370 patients with median age of 55 years old were recruited in the study. The male-to-female ratio was 1.3∶1. Among the 361 patients who underwent therapy, 280 cases received chemotherapy alone, 65 cases received chemoradiotherapy, and 16 cases received chemotherapy combined with autologous hematopoietic stem cell transplantation (AHSCT). The median follow-up period was 89 months, the 5-year overall survival (OS) rate of the entire cohort was 42.9%. The 5-year OS rate of chemotherapy alone, chemoradiotherapy and chemotherapy combined with AHSCT were 36.8%, 58.5%, 87.5%, respectively. The 5-year OS rate were significantly different between chemoradiotherapy and chemotherapy alone (P=0.001), and between chemotherapy combined with AHSCT and chemoradiotherapy (P=0.040). Univariate analysis showed that the age, Eastern Cooperative Oncology Group performance status (ECOG PS) score, Ann Arbor stage, B symptom, bulky disease, number of extranodal sites, Ki-67 index, lactate dehydrogenase (LDH), ß2-microglobulin (ß2-MG), international prognostic index (IPI), therapeutic manner and chemotherapy combined with rituximab were significantly associated with the prognosis of advanced DLBCL patients (all P<0.05). Multivariate analysis demonstrated that the age >60 years, Ann Arbor stage IV, with B symptom, with bulky disease, ECOG PS≥1, Ki-67 index > 90%, CD5 expression, up-regulation of serum LDH and ß2-MG, and chemotherapy without rituximab were related with the poor prognosis of patients with advanced-stage DLBCL (all P<0.05). Conclusions: Chemotherapy combined with rituximab can improve the outcome of patients with advanced-stage DLBCL. The age, stage, B symptom, bulky disease, ECOG PS score, Ki-67 index, CD5 expression, LDH, ß2-MG and chemotherapy combined with rituximab are associated with the prognosis of these patients.

[Prognostic significance of inflammatory indicators for advanced-stage diffuse large B-cell lymphoma].

Objective: To explore the prognostic significance of inflammatory indicator, neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR), for advanced-stage diffuse large B-cell lymphoma (DLBCL). Methods: The data of advanced stage DLBCL cases was retrospectively collected, and all the patients were seen from January 2006 to December 2012 in National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences. The patients were divided into the low NLR group (≤5∶1) and the high NLR group (>5∶1); the low PLR group (≤300∶1) and the high PLR group (>300∶1). Kaplan-Meier method was used to compare the survival rates between groups, multivriate Cox proportional hazard regression analysis was performed to assess the independent prognostic significance of clinical and histopathological variables on events or OS. Results: A total of 361 patients were included in the study. Under a median follow-up of 89 months, the 5-year overall survival (OS) and progression-free survival (PFS) of the whole group were 42.9% and 31.3%, respectively. The 5-year OS rate and PFS rate were 48.2% and 35.1% in the low NLR group, which were 24.1% and 17.7% in the high NLR group, respectively. The 5-year OS rates and PFS rate were 45.4% and 33.2% in the low PLR group, which were 29.8% and 21.1% in the high PLR group (all P<0.05). Univariate analysis showed that NLR >5∶1, PLR >300∶1, age>60 year, ECOG PS>1 score, stage Ⅳ, B symptom, bulky disease, number of extranodal sites >1, Ki-67index >90%, LDH elevated and ß2-MG elevated had significant influence on prognosis(all P<0.05). Multivariate analysis demonstrated that NLR, stage, B symptom, bulky disease, ECOG PS score, Ki-67 index and ß2-MG were associated with poor prognosis in the advanced-stage DLBCL. Conclusions: NLR was simple and feasible biomarker for prognosis of advanced-stage DLBCL patients.

Polymorphisms in the LPL gene and their association with growth traits in Jiaxian cattle.

Previous studies showed that the lipoprotein lipase (LPL) gene was involved in metabolism and transport of lipids, suggesting that the LPL is a potential candidate gene affecting growth traits in animals. The aim of this study was to identify polymorphism in the bovine LPL gene and analyze its possible association with growth traits in 218 randomly selected Jiaxian cattle. We used DNA sequencing to identify single nucleotide polymorphisms (SNPs) in the LPL gene. A sequence analysis revealed three SNPs: two in intron 5 (C18306T and C18341T) and one in exon 6 (G18362A). G18362A is a missense mutation leading to a change of the 325th glycine to serine. Based on χ(2) tests, the genotypic distributions of C18306T were in agreement with the Hardy-Weinberg equilibrium (P > 0.05), whereas the other two mutations were not (0.05 > P > 0.01). Association analyses showed that the C18341T SNP was significantly associated with several growth traits (P < 0.01 or P < 0.05), and the G18362A was associated with withers height (P < 0.05). Our results suggest that LPL gene variation may be considered molecular markers for growth traits in Jiaxian cattle.

Expression and clinical significance of the obesity-related gene TNFAIP9 in obese children.

To investigate the expression of tumor necrosis factor-alpha inducible protein 9 (TNFAIP9) gene in obese children and its clinical significance, 36 simple obese children and 17 non-obese children were recruited as research subjects. The adipose tissue was obtained by abdominal operation. The expression of TNFAIP9 was detected using real-time fluorescence quantitative polymerase chain reaction and western blot. The relationship between the expression of TNFAIP9 and blood lipid, blood glucose, and obesity indexes was analyzed. The levels of TNFAIP9 mRNA and protein in obese children were significantly lower than those in the control group (P < 0.05). The waist circumference (wc), body mass, body mass index (BMI), fat, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), insulin resistance index (HOMA-IR), and endothelin (ET) in obese children were significantly higher than those in the control group. The level of high-density lipoprotein cholesterol (HDL-C) was significantly lower than that in the control group (P < 0.05). The level of TNFAIP9 protein was negatively correlated with the wc, body mass, BMI, fat, TC, TG, LDL-C, HOMA-IR, and ET (P < 0.05) and was positively correlated with the level of HDL-C (P < 0.05). In conclusion, the expression of TNFAIP9 significantly decreased in the adipose tissue of obese children, and its levels are closely related to blood lipid level, insulin resistance, and obesity.

[Clinical features and prognosis of CD20-positive classical Hodgkin lymphoma].

OBJECTIVE: To explore the clinical characteristics and prognosis of CD20-positive classical Hodgkin lymphoma (CHL). METHODS: Data from CHL patients with CD20 immunohistochemical staining result who were treated in Cancer Hospital of Chinese Academy of Medical Sciences between September 2007 and March 2014 were reviewed. The relationship of CD20 expression in Reed-Sternberg(R-S)cells with CHL subtypes, clinical characteristics, and prognosis were analyzed. Fisher test was used to analyze the differences between groups and Kaplan-Meier for survival analysis. RESULTS: A total of 263 patients were included in this study. Among the 263 patients, 74 (28.1%) were CD20-postitive. CD20-positive cases showed significantly higher proportions of Epstein-Barr virus (EBV) infection-related, mixed cellularity, and lymphocyte-rich CHL subtypes compared with CD20-negeative patients [52.8% (28/53) vs 19.0% (22/116), 37.9% (25/66) vs 31.6% (54/171), 22.7% (15/66) vs 3.5% (6/171), all P<0.05]. Univariate analysis identified EBV infection, age (≥ 40 years, especially ≥ 60 years), and Ⅲ-Ⅳ stage were correlated with reduced 3-year progression-free survival (PFS) and overall survival (OS) (PFS: 70.3 vs 87.7%, 79.2% vs 89.8%, 56.8% vs 91.5%, 70.4% vs 93.2%; OS: 81.0% vs 100%, 92.1% vs 99.4%, 75.4% vs 99.2%, 90.3% vs 100%; all P<0.05); and CD20-positive and not receiving local radiotherapy were associated with reduced PFS (79.7% vs 90.6%, 68.8% vs 90.6%, both P<0.05), not with OS (92.4% vs 98.3%, 94.0% vs 99.4%, both P>0.05). Patients positive in both CD20 expression and EBV-encoded small RNAs (EBER) showed low PFS. CONCLUSIONS: CD20 expression in R-S cells in CHL may be closed related with EBV infection. EBV infection is associated with unfavorable prognosis. The effect of CD20-postitive on prognosis may be mediated by the prognostic effect of EBV infection.

A last stand in the Po valley: genetic structure and gene flow patterns in Ulmus minor and U. pumila.

BACKGROUND AND AIMS: Ulmus minor has been severely affected by Dutch elm disease (DED). The introduction into Europe of the exotic Ulmus pumila, highly tolerant to DED, has resulted in it widely replacing native U. minor populations. Morphological and genetic evidence of hybridization has been reported, and thus there is a need for assessment of interspecific gene flow patterns in natural populations. This work therefore aimed at studying pollen gene flow in a remnant U. minor stand surrounded by trees of both species scattered across an agricultural landscape. METHODS: All trees from a small natural stand (350 in number) and the surrounding agricultural area within a 5-km radius (89) were genotyped at six microsatellite loci. Trees were morphologically characterized as U. minor, U. pumila or intermediate phenotypes, and morphological identification was compared with Bayesian clustering of genotypes. For paternity analysis, seeds were collected in two consecutive years from 20 and 28 mother trees. Maximum likelihood paternity assignment was used to elucidate intra- and interspecific gene flow patterns. KEY RESULTS: Genetic structure analyses indicated the presence of two genetic clusters only partially matching the morphological identification. The paternity analysis results were consistent between the two consecutive years of sampling and showed high pollen immigration rates (∼0·80) and mean pollination distances (∼3 km), and a skewed distribution of reproductive success. Few intercluster pollinations and putative hybrid individuals were found. CONCLUSIONS: Pollen gene flow is not impeded in the fragmented agricultural landscape investigated. High pollen immigration and extensive pollen dispersal distances are probably counteracting the potential loss of genetic variation caused by isolation. Some evidence was also found that U. minor and U. pumila can hybridize when in sympatry. Although hybridization might have beneficial effects on both species, remnant U. minor populations represent a valuable source of genetic diversity that needs to be preserved.

Identification of single nucleotide polymorphisms of the signal transducer and activator of transcription 3 gene (STAT3) associated with body measurement and carcass quality traits in beef cattle.

Previous studies have shown that the signal transducer and activator of transcription 3 gene (STAT3) is involved in lipid storage and energy metabolism, suggesting that STAT3 is a potential candidate gene that affects body measurement and carcass quality traits in animals. Therefore, the aim of this study was to identify polymorphisms in bovine STAT3 and to analyze their possible associations with body measurement and carcass quality traits in 493 individuals of 2 native Chinese cattle breeds: Qinchuan (N = 371) and Jiaxian cattle (N = 122). DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were employed to detect STAT3 single nucleotide polymorphisms (SNPs). We found 5 SNPs: 1 in an exon (g.65812G>A: exon 16) and 4 in introns (g.43591G>A: 13 intron, g.67492T>G: 19 intron, g.67519T>C: 19 intron, and g.68964G>A: 20 intron). Both g.65812G>A and g.68964G>A were not in Hardy- Weinberg equilibrium (HWE), whereas individual frequencies of each genotype were consistent with HWE for other SNPs in Qinchuan cattle populations. For the Jiaxian cattle, the genotype distributions of the 4 mutations were in HWE except for g.67519T>C. The results indicate that these SNPs have a significant association with some body measurements and carcass quality traits (P < 0.05 or P < 0.01). Therefore, STAT3 might have potential effects on production traits in beef cattle populations and could be used for marker-assisted selection.

Forkhead box protein O1 mediates apoptosis in a cancer cervical cell line treated with the antitumor agent tumor necrosis factor-α.

Tumor necrosis factor-α (TNF-α) is an important pro-apoptotic cytokine, which performs a broad range of immune and inflammatory functions in several vital processes. TNF-α-induced apoptosis has been confirmed, however, relatively little is known regarding the role of forkhead box class-O 1 (FOXO1) in mediating TNF-α-induced apoptosis in cervical cancer. In our study, we used the well-characterized cervical cancer cell line C-33A to investigate the role of FOXO1. The results showed that the antitumor agent TNF-α increased the expression level of FOXO1 (P < 0.05) and enhanced its transcriptional activity (P < 0.05). Furthermore, knockdown of FOXO1 repressed TNF-α-induced apoptosis and caspase-3, 8, and 9 expressions (P < 0.05). Collectively, these findings suggest that TNF-α upregulated the transcriptional factor FOXO1, leading to an increased expression of apoptotic gene, which leads to an increase in apoptosis.

Polymorphisms in the SIRT5 gene and their association with body measurement and ultrasound traits in Qinchuan cattle.

Silent information regulator 5 (SIRT5), a member of the Sirtuin family class III nicotinamide adenine dinucleotide-dependent protein deacetylases, plays an important role in metabolic and aging processes in mammals. We identified 4 single-nucleotide polymorphisms (SNPs) (G22010A, G22052A, G22119T, and G22245C) in the 3' untranslated regions of the SIRT5 gene from 572 Qinchuan cattle by sequencing and investigating their association with growth and ultrasound traits. The frequencies of genotype GG and allele G were high at the 4 SNPs. Based on the X(2) test, the genotypic distributions of the 4 SNPs were not in Hardy-Weinberg equilibrium (P < 0.05 or P < 0.01). Association analysis of individual SNPs and haplotype combinations revealed that the 4 loci were significantly associated with some body measurement and ultrasound traits in Qinchuan cattle, and the H1H5 (AG-GA-GG-GG) diplotypes had better performance than other combinations in Qinchuan cattle. Our results demonstrate that SIRT5 may be a candidate for marker-assisted selection in future breeding programs for Qinchuan cattle.

Association of CRTC2 gene polymorphisms with growth and meat quality traits of Qinchuan cattle.

Growth and meat quality traits play important roles in the evaluation of cattle productivity and are influenced by genetic and environmental factors. CRTC2 is a recently discovered gene related to obesity that may influence fat deposition. The aim of the current study was to detect polymorphisms of bovine CRTC2 and explore their relationships to growth and meat quality in Qinchuan cattle. Three single nucleotide polymorphisms (SNPs); g.3001 C>T; g.3034 G>A; and g.3467 T>C, were identified from sequencing results of 422 Qinchuan cattle. The genotypic distributions of both g.3034 G>A and g.3467 T>C mutations were in agreement with Hardy-Weinberg equilibrium, (P < 0.05), while the T3001C mutation was not (P > 0.05), based on χ(2) test analysis. The SNPs g.3001 C>T and g.3034 G>A are missense mutations (Ser/Phe and Ser/Thr respectively). Additionally, SNPs g.3034 G>A and g.3467 T>C showed a medium polymorphism level (0.25 < PIC< 0.50), whereas g.3001 C>T showed a low polymorphism level (PIC < 0.25). These three SNPs were significantly associated with several growth and meat quality traits in the Qinchuan cattle population (P < 0.05 or P < 0.01). Collectively, these results demonstrate that CRTC2 is involved in the regulation of cattle growth and meat quality, and suggest that CRTC2 is a potential candidate gene for marker-assisted selection in future breeding development programs for Qinchuan cattle.

FOXO1 is a tumor suppressor in cervical cancer.

Forkhead box protein O1 (FOXO1) is an important transcriptional regulator of cell proliferation, and is considered essential for tumor growth and progression. However, the function of FOXO1 in human cervical cancer remains unclear. In this study, we investigated the role of FOXO1 in cervical cancer. Our results showed that FOXO1 expression was lower in cervical cancer than in cervical intraepithelial neoplasia and normal cervix by immunohistochemical analysis (P < 0.05). The level of FOXO1 in high-grade lesions was significantly lower than in low-grade lesion (P < 0.05), indicating that deficient expression of FOXO1 is involved in tumor progression and significantly associated with late-stage tumors (P < 0.05), which was further supported by clinicopathological, real-time polymerase chain reaction, and Western blotting analysis. Moreover, we confirmed that the overexpression of FOXO1 remarkably repressed cell growth and blocked cell proliferation, accompanied by cell-cycle arrest in the G2/M phase and upregulation of caspases-3 and -9 gene expression. Collectively, our data suggest that FOXO1 plays a vital role in inhibiting cervical cancer development by inducing cell-cycle arrest and apoptosis. FOXO1 expression is a favorable prognostic factor for human cervical cancer.