[Application of the China-PAR stroke risk equations in a rural northern Chinese population].

OBJECTIVE: To validate five-year risk prediction models for stroke in a contemporary rural Northern Chinese population. METHODS: Totally 6 483 rural adults aged 40 to 79 years without cardiovascular diseases were enrolled at baseline between June and August 2010, and followed up through January 2017. Expected prediction risk using the China-PAR (prediction for atherosclerotic cardiovascular disease risk in China) stroke risk equations were compared with the new Framingham stroke risk profile (FSRP). The recalibrated models were applied by adjusting the five-year baseline survival rate and the mean score to our rural northern Chinese population, while keeping other coefficient parameters the same as the original models. Kaplan-Meier analysis was used to obtain the observed event (nonfatal or fatal stroke) rate for the five years, and the expected-observed ratios were calculated to evaluate overestimation or underestimation in the cohort. The models were assessed by discrimination C statistic, calibration χ2, and calibration charts and plots for illustration as well. RESULTS: Over an average of (5.83 ± 1.14) years of the follow-up in this validation cohort with 6 483 rural Chinese participants, 438 subjects deve-loped a first stroke event. Recalibrated China-PAR stroke risk equations and FSRP well-performed for predicting five-year stroke risk in men, and had C statistics of 0.709 (95%CI, 0.675 - 0.743) and 0.721 (95%CI, 0.688 - 0.754), with calibration χ2 values being 5.7 (P = 0.770) and 13.6 (P = 0.137), respectively. However, both China-PAR and FSRP overestimated stroke events by 11.6% and 30.0% in women, and had C statistics of 0.713 (95%CI, 0.684-0.743) and 0.710 (95%CI, 0.679-0.740), respectively. Calibration χ2 values in women were 12.5 (P = 0.188) for China-PAR and 24.0 (P = 0.004) for FSRP. In addition, the calibration charts and plots illustrated good agreement between the observations and the predictions only in the China-PAR stroke risk equations, especially for men. CONCLUSION: In this validation cohort of rural northern Chinese adults, the China-PAR models had better performance of five-year stroke risk prediction than the FSRP, indicating that recalibrated China-PAR stroke risk equations might be appropriate tools for risk assessment and primary prevention of stroke in China.

[Application of the China-PAR risk prediction model for atherosclerotic cardiovascular disease in a rural northern Chinese population].

OBJECTIVE: To validate five-year risk prediction models for atherosclerotic cardiovascular disease (ASCVD) in a contemporary rural Northern Chinese population. METHODS: Totally 6 489 rural adults aged 40 to 79 years without clinical ASCVD were enrolled at baseline between June and August 2010, and followed up through January 2017. Expected prediction risk using the China-PAR (prediction for ASCVD risk in China) model was compared with the pooled cohort equations (PCE) reported in the American College of Cardiology/American Heart Association guideline. Kaplan-Meier analysis was used to obtain the observed ASCVD event (including nonfatal myocardial infarction, coronary heart disease death, nonfatal or fatal stroke) rate at 5 years, and the expected-observed ratios were calculated to eva-luate overestimation or underestimation in the cohort. The participants in the cohort were divided into 4 categories (<5.0%, 5.0%-7.4%, 7.5%-9.9%, and ≥10.0%) for comparisons based on ASCVD prediction risk. The models were assessed by discrimination C statistic, calibration χ2, and calibration charts and plots for illustration as well. RESULTS: Over an average 5.82 years of follow-up in this validation cohort with 6 489 rural Chinese participants, 955 subjects developed a first ASCVD event. Recalibrated China-PAR model overestimated ASCVD events by 22.2% in men and 33.1% in women, while the overestimations were much higher for recalibrated PCE as 67.3% in men and 53.1% in women. Gender-specific China-PAR model had C statistics of 0.696 (95%CI, 0.669-0.723) for men and 0.709 (95%CI, 0.690-0.728) for women, which were similar to those of 0.702 (95%CI, 0.675-0.730) for men and 0.714 (95%CI, 0.695-0.733) for women in the PCE. Calibration χ2 values in China-PAR were 17.2 and 54.2 for men and women, respectively; however, the PCE showed poorer ca-libration (χ2=192.0 for men and χ2=181.2 for women). In addition, the calibration charts and plots illustrated good agreement between the observations and the predictions only in the China-PAR model, especially for men. CONCLUSION: In this validation cohort of rural Northern Chinese adults, the China-PAR model had better performance of five-year ASCVD risk prediction than the PCE, indicating that recalibrated China-PAR model might be an appropriate tool for risk assessment and primary prevention of ASCVD in China.

[Relationship between glycemic control and visceral adiposity index among the patients with type 2 diabetes mellitus].

OBJECTIVE: To explore the relationship between glycemic control and visceral adiposity index (VAI) among type 2 diabetes mellitus (T2DM) patients. METHODS: A community-based epidemiological field study for patients with T2DM aged ≥ 40 years was conducted in China.Every participant underwent physical examinations, biochemical tests of fasting glucose, glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and so on, and a questionnaire, including anthropometric characteristics, lifestyle, disease history, family history, and medication use. Those participants with HbA1c ≥7.0% were classified as the poorly controlled in our analysis of relationship between glycemic control and VAI. Anthropometric characteristics, lifestyle, and biochemical indexes of the participants were compared among the groups of different VAI levels. Logistic models were applied in multiple analysis adjusting for possible confounders. RESULTS: A total of 1 607 patients with T2DM were recruited in our analysis with a mean age of (59.4±8.1) years and an average T2DM duration of (7.0±6.4) years. Among them, 78.3% were on hypoglycemic therapy. The cutoff points of quartiles of VAI were calculated for the males and females, respectively. According to the ascending order of the quartiles of VAI, the participants were divided into four groups, i.e. Q1, Q2, Q3, and Q4. The poor glycemic control rate for these groups were 60.6%, 65.7%, 70.1%, and 71.0%, respectively (Trend χ2=12.20, P<0.001). After adjustment for age, gender, systolic blood pressure (SBP), diastolic blood pressure (DBP), LDL-C, smoking, cardio-cerebral vascular disease (CVD) history, hypoglycemic therapy, T2DM duration, and family history of diabetes, the Logistic regression models showed that the glycemic control rate was significantly associated with VAI levels among the patients with T2DM. Compared with the participants in group Q1, the ORs of poor glycemic control for those in groups Q2, Q3, and Q4 were 1.239 (95%CI 0.918 to 1.672), 1.513 (95%CI 1.117 to 2.050), and 1.535 (95%CI 1.128 to 2.088), respectively (trend P=0.003). With each quartile increase in VAI, the OR of poor glycemic control was 1.162 (95%CI 1.054 to 1.282). CONCLUSION: The glycemic control among the patients with T2DM is significantly associated with VAI. High level of VAI is an indicator of poor glycemic control.

Association analysis between feed efficiency studies and expression of hypothalamic neuropeptide genes in laying ducks.

Residual feed intake (RFI) is now considered a more reasonable metric to evaluate animal feed efficiency. In this study, the correlation between RFI and other feed efficiency traits was investigated and gene expression within the hypothalamus was determined in low RFI (LRFI) and high RFI (HRFI) ducks. Further, several hypothalamic neuropeptide genes were measured using quantitative real-time PCR. The mean feed intake value was 160 g/day, whereas the egg mass laid (EML) and body weight were approximately 62.4 g/day and 1.46 kg respectively. Estimates for heritability of RFI, feed conversion ratio (FCR) and feed intake were 0.26, 0.18 and 0.23 respectively. RFI is phenotypically positively correlated with feed intake and FCR (P < 0.01). The expression of neuropeptide Y (NPY) and neuropeptide Y receptor Y5 (NPY5R) mRNA was higher in HRFI ducks compared with LRFI ducks (P < 0.05), whereas that of proopiomelanocortin (POMC), melanocortin 4 receptor (MC4R) and cholecystokinin (CCK) was lower (P < 0.05). The mRNA expression of gonadotropin-releasing hormone 1 (luteinizing-releasing hormone) (GNRH1) and prolactin receptor (PRLR) was unchanged between LRFI and HRFI ducks. The results indicate that selection for LRFI could reduce feed intake without significant changes in EML, whereas selection on FCR will increase EML.

[Effect of 50 mg alteplase to intermediate-risk pulmonary embolism with right ventricular dysfunction].

Objective: To investigate the effect of 50 mg alteplase to intermediate-risk acute pulmonary embolism (APE) with right ventricular dysfunction. Methods: From May 2011 to May 2015, a total of 73 patients with intermediate-risk APE, furthermore, right ventricular systolic pressure (RVSP)>40 mmHg and B-type natriuretic peptide (BNP)>100 ng/L, were allocated to receive 50 mg alteplase plus anti-coagulation (thrombolysis group, TG, n=35) or anticoagulation alone (control group CG, n=38) according to their will.Tricuspid annular plane systolic excursion (TAPSE), Right ventricular fractional area change (RVFAC), RVSP, BNP, CT obstruction index (CTOI) were detected at prior treatment, 1st day, 14th day, 3rd month, 6th month. The adverse events consisting of hemodynamic decompensation (within 14 days), mortality, bleeding, recurrent pulmonary embolism (PE), RVSP>40 mmHg (at 6th month) were recorded. Results: At prior treatment, TAPSE, RVFAC, RVSP, BNP and CTOI between TG and CG were (10.9±1.4) vs (11.4±1.2) mm, (27.8±3.9)% vs (28.1±4.1)%, (55.6±7.9) vs (54.6±8.4) mmHg, (491±76) vs (482±71) ng/L and (23.4±4.2)% vs (23.7±4.5)%. There was not statistical difference between two groups (all P>0.05). From 1st to 14th day, these indexes had better and faster improvement in TG than CG. At 6th month, TAPSE, RVFAC, RVSP and CTOI between two groups were (17.5±1.3) vs (15.4±1.1) mm, (49.4±3.9)% vs (46.0±2.8)%, (15.8±2.2) vs (17.8±4.2) mmHg, and (1.7±1.6)% vs (4.0±3.0)% (all P<0.05), BNP was (66±13) vs (71±15) ng/L (P>0.05). From prior treatment to 6th month, the tendency of variation of these index in TG was better than CG (P<0.05). From prior treatment to 14th day, 3 cases of hemodynamic decompensation occurred in CG, 0 case in TG.During treatment, there were not cases of death and major bleeding. At 6th month, there were 4 cases of RVSP>40 mmHg in CG, while 0 case in TG (P=0.048). Conclusion: 50 mg alteplase can reduce the thrombus in pulmonary artery, improve right ventricular function quickly, and decrease the risk of elevated RVSP in the long term, for the patients with intermediate-risk APE.

First Report of Lasiodiplodia theobromae Associated with Stem Canker of Cassia fistula in Guangxi, South China.

Cassia fistula, a member of the Fabaceae, known as the golden shower tree, is native to South Asia. It is now distributed worldwide and is popular as an ornamental plant as well as being used in herbal medicine. In October 2013, symptoms of stem canker were observed on C. fistula in a nursery (108°38' E, 22°87' N) in Nanning, Guangxi, China. The symptoms began as small brown lesions, which enlarged over several months to long, striped, slightly sunken lesions, 1 to 9 cm in width and 16 to 135 cm in length. The conspicuous cankers had vertical cracks outlining the canker and evenly spaced horizontal cracks, eventually resulting in whole plants dying back. The cankers were found on 90% of six-year-old plants in this nursery and were also observed in other plantings. On potato dextrose agar (PDA), isolates with similar morphological characteristics were consistently recovered from symptomatic plant tissues after surface sterilization in 75% ethanol for 30 sec and then in 0.1% mercuric chloride for 2 min. Over 100 conidia were examined from three isolates and were found to be elliptical and hyaline when immature, becoming dark brown, one-septate, and longitudinally striate when mature and ranging from 20 to 31 × 11 to 16 µm (average 25.5 × 13.6 µm). The rDNA internal transcribed spacer (ITS) region of isolate LC-1 was sequenced (GenBank Accession No. KM387285), and it showed 100% identity to Lasiodiplodia theobromae (Pat.) Griffon & Maubl. (GenBank KC964548), confirming the morphological identification (2) as L. theobromae (also known as Botryosphaeria rhodina (Cooke) Arx). A culture of this isolate has been preserved in the Guangxi Academy of Agricultural Sciences fungal collection. The pathogenicity of the isolate was tested on healthy twigs and branches of C. fistula trees in a field setting at Guangxi Agricultural Vocational-Technical College, Nanning, Guangxi, in June and August 2014. For each treatment, five green twigs and five 2-year-old branches were used. Five adjacent needle punctures were made on each branch with a sterilized needle. A mycelial plug was then placed on the wound of each branch and wrapped with Parafilm. Control twigs were treated with sterile PDA plugs. One week later, typical lesions were observed on the inoculated branches, with symptoms becoming more extensive after two weeks, but no symptoms were seen on the controls. Koch's postulates were fulfilled by re-isolation of L. theobromae from diseased branches. L. theobromae is recognized as an important wood pathogen and has been reported to cause cankers, dieback, and fruit and root rots in over 500 different hosts, including perennial fruit and nut trees, vegetable crops, and ornamental plants (2). The fungus has been reported on C. fistula in India since the 1970s (1); however, to our knowledge, this is the first report of L. theobromae infecting C. fistula in China. References: (1) R. S. Mathur. The Coelomycetes of India. Bishen Singh Mahendra Pal Singh, Delhi, India, 1979. (2) J. R. Úrbez-Torres et al. Plant Dis. 92:519, 2008.

The impact of metabolic syndrome on the responsiveness to α1-blocker in men with BPH/LUTS.

AIMS: Increasing evidence has proposed the components of metabolic syndrome (MtS) as risk factors for the development of benign prostate hyperplasia (BPH); therefore, it is thought that MtS may play a role in lower urinary tract symptoms related to BPH (BPH/LUTS) aetiology. Considering the closed relationships between MtS and BPH/LUTS, it is possible that patients with MtS might have different drug responsiveness in men with BPH/LUTS. We prospectively investigated the impact of MtS on responsiveness to α1-blocker in men with BPH/LUTS. METHODS: We enrolled a total of 109 patients with a mean (SD) age of 59.8 (9.0) years, having a prostate volume of 20 cm(3) or greater with moderate to severe LUTS. All patients received doxazosin GITS (gastrointestinal therapeutic system) 4 mg once daily for a 12-week period of treatment. The efficacy measurement was assessed by the changes from baseline in the total IPSS, maximum urinary flow rate and postvoid residual urine volume. The drug responders were defined as those who had a total IPSS decrease of more than 4 points from baseline after 12 weeks of treatment. RESULTS: Using multiple logistic regression analysis, our results showed that MtS was an independent factor for drug non-responder (OR = 4.26, p = 0.002). The rate of drug responder and total IPSS improvements in patients with MtS significantly decreased as the number of MtS components increased (p = 0.012 and p = 0.026). Among the MtS components, abnormal fasting blood glucose (FBG) was the most significantly independent factor for drug non-responder (OR = 3.17, p = 0.020). CONCLUSION: This study suggested that the presence of MtS had a significantly negative impact on the responsiveness to α1-blocker in men with BPH/LUTS. Our results are important for BPH/LUTS patients who did not initially respond to α1-blocker or who strive to reduce these metabolic risk factors.

First Report of Leaf Spot Disease Caused by Glomerella magna on Lobelia chinensis in China.

Lobelia chinensis is a perennial herbaceous plant in the family Campanulaceae that is native to China, where it grows well in moist to wet soils. It is commonly used as a Chinese herbal medicine. In May 2012, symptoms of leaf spot were observed on leaves of L. chinensis in Nanning, Guangxi Zhuang Autonomous Region, China. The leaf lesions began as small, water-soaked, pale greenish to grayish spots, which enlarged to gray to pale yellowish spots, 4 to 6 mm in diameter. At later stages, numerous acervuli appeared on the lesions. Acervuli were mostly epiphyllous, and 40 to 196 µm in diameter. On potato dextrose agar (PDA), a fungus was consistently recovered from symptomatic leaf samples, with a 93% isolation rate from 60 leaf pieces that were surface sterilized in 75% ethanol for 30 s and then in 0.1% mercuric chloride for 45 s. Three single-spore isolates were used to evaluate cultural and morphological characteristics of the pathogen. Setae were two to three septate, dark brown at the base, acicular, and up to 90 µm long. Conidia were long oblong-elliptical, guttulate, hyaline, and 11 to 20 × 4.1 to 6.3 µm (mean 15.2 × 5.1 µm). These morphological characteristics of the fungus were consistent with the description of Colletotrichum magna (teleomorph Glomerella magna Jenkins & Winstead) (1). The rDNA internal transcribed spacer (ITS) region of one isolate, LC-1, was sequenced (GenBank Accession No. KC815123), and it showed 100% identity to G. magna, GenBank HM163187.1, an isolate from Brazil cultured from papaya (2). Although KC815123 was identified as G. magna, it shows 99% identity to GenBank sequences from isolates of C. magna, and more research is needed to elucidate the relationships between these taxa, especially with consideration to host specificity. Pathogenicity tests were performed with each of the three isolates by spraying conidial suspensions (1 × 106 conidia/ml) containing 0.1% Tween 20 onto the surfaces of leaves of 30-day-old and 6- to 8-cm-high plants. For each isolate, 30 leaves from five replicate plants were treated. Control plants were treated with sterilized water containing 0.1% Tween 20. All plants were incubated for 36 h at 25°C and 90% relative humidity in an artificial climate chamber, and then moved into a greenhouse. Seven days after inoculation, gray spots typical of field symptoms were observed on all inoculated leaves, but no symptoms were seen on water-treated control plants. Koch's postulates were fulfilled by reisolation of G. magna from diseased leaves. To our knowledge, this is the first report of G. magna infecting L. chinensis worldwide. References: (1) M. Z. Du et al. Mycologia 97:641, 2005. (2) R. J. Nascimento et al. Plant Dis. 94:1506, 2010.

First Report of Leaf Spot Caused by Corynespora cassiicola on Baphicacanthus cusia in China.

Baphicacanthus cusia is a perennial herbaceous plant in the family Acanthaceae that is native to China, where it grows in warm temperate mountainous or hilly regions. It is commonly used as a Chinese herbal medicine. In March 2012, symptoms of leaf spot were observed on leaves of B. cusia in Long'an County, Guangxi, China, where this plant is extensively cultivated. Symptoms were initially small brown dots which developed into irregular to circular leaf spots. These spots enlarged and overlapped, extending until the 7- to 9-cm-long and 3- to 4-cm-wide leaves withered entirely, mostly within 2 months. On potato dextrose agar (PDA), the same fungus was cultured from 92% of 75 symptomatic leaf samples that had been surface sterilized in a 45-second dip in 0.1% mercuric chloride. Fungal structures were observed on diseased leaves: conidiophores (85 to 460 × 4 to 8 µm) were erect, brown, single or in clusters, and conidia (36 to 90 × 5 to 16 µm) were single or in chains of two to four, brown, cylindrical or obclavate, straight or slightly curved, with 3 to 18 pseudosepta and a conspicuous hilum. Three single-spore isolates were identified as Corynespora cassiicola (Berk & Curt.) Wei based on morphological and cultural characteristics (1). The rDNA internal transcribed spacer (ITS) region of one isolate, ZY-1, was sequenced (GenBank Accession No. JX908713), and it showed 100% identity to C. cassiicola, GenBank FJ852716, an isolate from Micronesia cultured from Ipomoea batatas (2). Pathogenicity tests were performed with each of the three isolates by spraying conidial suspensions (5 × 104 conidia/ml) containing 0.1% Tween 20 onto the surfaces of leaves of 60-day-old, 20-cm tall plants. For each isolate, 30 leaves from five replicate plants were treated. Control plants were treated with sterilized water containing 0.1% Tween 20. All plants were incubated for 36 h at 25°C and 90% relative humidity in an artificial climate chamber, and then moved into a greenhouse. Seven days after inoculation, dark brown spots typical of field symptoms were observed on all inoculated leaves, but no symptoms were seen on water-treated control plants. Koch's postulates were fulfilled by reisolation of C. cassiicola from diseased leaves. To our knowledge, this is the first report of C. cassiicola infecting B. cusia worldwide. References: (1) M. B. Ellis. Dematiaceous Hyphomycetes. Commonwealth Mycological Institute: Kew, Surrey, England, 1971. (2) L. J. Dixon et al. Phytopathology 99:1015, 2009.

An Outbreak of Gummosis of Mango Trees Caused by Lasiodiplodia theobromae in Guangxi, South China.

Mango (Mangifera indica L.) is an economically important fruit in southern provinces of China. In May 2012, field surveys including 2,250 mango trees were done in nine orchards of five different counties in Guangxi Province. An outbreak of gummosis was observed in the province involving over 30,000 ha with an average of 50% disease incidence (DI) and a maximum of 70% in some orchards. Until then, gummosis had been considered a common but not serious disease. In 2012, high temperatures in April and extensive rain in May favored increased disease development. Infected plants showed abundant gum secretion from branches, stems, and main trunks. Some branches died from the disease. During the early stages of infection, branches or stems turned brown followed by xylem necrosis and exudation of a milky sap. The sap turned yellow and finally formed amber gum within several days. Initially, the gum appeared as small droplets, increasing in number, and covering most of the branches and the trunk with bark cracking under severe conditions. On potato dextrose agar (PDA), isolates with similar morphology were consistently recovered from symptomatic plant tissues after surface sterilization in 75% ethanol for 30 seconds and then in 0.1% mercuric chloride for 1 min. Five single-spore isolates from five different locations in Guangxi Province were used to evaluate characteristics of the pathogen. On PDA, cultures were gray with an irregularly distributed, fast-growing, and fluffy aerial mycelium, showing a dark underside as the colony changed from greenish to black after 5 days at 28°C. After 1 month, cultures produced globose pycnidia. Conidia were elliptical and hyaline when immature, becoming dark brown and one-septate, longitudinally striate when mature, and ranged from 20.0 to 28.0 × 10.5 to 16.0 µm (average 23.3 × 13.7 µm). Paraphyses produced within the tissues of pycnidia were hyaline, cylindrical, nonseptate, and up to 61 µm long. The fungus was identified as Lasiodiplodia theobromae (Pat.) Griffon & Maubl. (=Botryosphaeria rhodina (Cooke) Arx) based on morphological and cultural characteristics (1,2). The rDNA internal transcribed spacer region of one isolate showed 100% identity to L. theobromae (GenBank HM346876.2) and was deposited in GenBank (JX982240). Pathogenicity of the five isolates was tested in the field on healthy tissues in June 2012. Five green twigs and five 3-year-old branches were used. Three wounds were made on each twig or branch with a sterilized needle. Mycelial plugs were placed on wounds and covered with Parafilm. Uncolonized PDA plugs were used as controls. Two weeks later, typical brown lesions were observed on inoculated branches, and gum exuded from infected wounds. No symptoms were seen on the controls. Koch's postulates were fulfilled by reisolation of L. theobromae from diseased branches. L. theobromae is well documented as a pathogen of mango. In China, the disease was observed in the 1990s in Hainan Province, and the causal agents were identified as L. theobromae and Colletotrichum gloeosporioides Penz. & Sacc based on morphological observation (3). To our knowledge, this is the most severe outbreak reported from China. References: (1) V. S. de Oliveira Costa et al. Eur. J. Plant Pathol. 127:509, 2010. (2) F. Wang et al. Plant Dis. 95:1378, 2011. (3) Q. C. Xiao et al. Tropical Crops Research (in Chinese) 2:25, 1995.

Genetic polymorphisms in androgen receptor-binding sites predict survival in prostate cancer patients receiving androgen-deprivation therapy.

BACKGROUND: Activated androgen receptor binds to androgen-responsive elements (AREs) in genome to regulate target gene transcription and, consequently, mediates physiological or tumorigenic processes of the prostate. Our aim was to determine whether genetic variants in AREs are associated with clinical outcomes after androgen-deprivation therapy (ADT) in prostate cancer patients. PATIENTS AND METHODS: We systematically investigated 55 common single-nucleotide polymorphisms (SNPs) in the genome-wide insilico-predicted AREs in a cohort of 601 men with advanced prostate cancer treated with ADT. The prognostic significance of these SNPs on disease progression, prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) after ADT was assessed by Kaplan-Meier analysis and Cox regression model. RESULTS: In univariate analysis, two, five, and four SNPs were associated with disease progression, PCSM, and ACM, respectively. After adjusting for known prognostic factors, ARRDC3 rs2939244, FLT1 rs9508016, and SKAP1 rs6504145 remained as significant predictors for PCSM and FBXO32 rs7830622 and FLT1 rs9508016 remained as significant predictors for ACM in multivariate analysis. Moreover, strong combined genotype effects on PCSM and ACM were also observed (P(trend) < 0.001). CONCLUSION: Our results suggest that SNPs in AREs influence prostate cancer survival and may further advance our understanding of the disease progression.

Genetic polymorphisms in oestrogen receptor-binding sites affect clinical outcomes in patients with prostate cancer receiving androgen-deprivation therapy.

BACKGROUND: Accumulating evidence indicates that oestrogens have significant direct effects on normal prostate development and carcinogenesis. The majority of the biological activities of oestrogens are mediated through the oestrogen receptor (ER), which functions as a hormone-inducible transcription factor to regulate target gene expression by binding to oestrogen response elements (EREs) in the regulatory regions of target genes. Sequence variants in EREs might affect the ER-ERE interaction and subsequent physiological activities. Therefore, we tested whether common single-nucleotide polymorphisms (SNPs) inside EREs are related to the clinical outcomes of androgen-deprivation therapy (ADT) in men with prostate cancer. METHODS: We systematically evaluated 49 ERE SNPs predicted using a genome-wide database in a cohort of 601 men with advanced prostate cancer treated with ADT. The prognostic significance of these SNPs on disease progression, prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) after ADT was assessed using Kaplan-Meier analysis and a Cox regression model. RESULTS: Based on multiple hypothesis testing, BNC2 rs16934641 was found to be associated with disease progression; in addition, TACC2 rs3763763 was associated with PCSM, and ALPK1 rs2051778 and TACC2 rs3763763 were associated with ACM. These SNPs remained significant in multivariate analyses that included known clinicopathological predictors. Moreover, a combined genotype effect on ACM was observed when ALPK1 rs2051778 and TACC2 rs3763763 were analysed in combination. Patients with a greater number of unfavourable genotypes had a shorter time to ACM during ADT (P for trend <0.001). CONCLUSION: The incorporation of ERE SNPs into models with known predictors might improve outcome prediction in patients with prostate cancer receiving ADT.

[Clinical prognostic analysis of 124 adult patients with hemophagocytic lymphohistiocytosis: a multicenter retrospective study of the Huaihai Lymphoma Working Group].

Objective: Factors influencing the prognosis of hemophagocytic lymphohistiocytosis (HLH) in adults were analyzed based on multicentric data. Methods: Clinical data of 124 adult patients with HLH diagnosed in eight medical centers in the Huaihai Lymphoma Working Group from March 2014 to July 2020 were collected. The optimal truncation value of continuous variables was obtained based on the Maxstat algorithm, X-Tile software, and restricted cubic spline. Cox proportional risk regression model was used to construct the adult HLH risk prediction model, and the visualization of the model was realized through the histogram. The bootstrap resampling method was used to verify the model, C-index and calibration curve was used to verify the histogram, and the prediction accuracy was checked. Kaplan-Meier analysis was used to calculate the survival rate and draw the survival curve. Furthermore, the differences between groups were tested by log-rank. Results: The median age of the 124 patients was 55 (18-84) years, including 61 (49.19%) males. The most common etiology was infection. Serum ferritin increased in 110 cases (88.71%) , hepatosplenomegaly in 57 cases (45.97%) . Of the 124 patients, 77 (62.10%) died, and the median survival time of the patients was 7.07 months. Univariate results showed that the prognosis of adult HLH was influenced by sex, age, fibrinogen, serum creatinine, alanine aminotransferase, and albumin (P<0.05) . The results of multivariate analysis showed that gender, platelet, albumin, alanine aminotransferase, and treatment regimens were independent influencing factors for prognosis. Based on the above five risk factors, the prediction model of the histogram was established, and the C-index of the model was 0.739. Finally, the calibration chart showed good consistency between the observed and predicted values of HLH. Conclusion: The prognosis of the adult hemophagocytic syndrome is influenced by many factors. Gender, platelet, albumin, alanine aminotransferase, and treatment regimens are independent risk factors. Therefore, the established histogram provides a visual tool for clinicians to evaluate the prognosis of adult HLH.

Dickkopf1 is required for embryonic head induction and limb morphogenesis in the mouse.

Dickkopf1 (Dkk1) is a secreted protein that acts as a Wnt inhibitor and, together with BMP inhibitors, is able to induce the formation of ectopic heads in Xenopus. Here, we show that Dkk1 null mutant embryos lack head structures anterior of the midbrain. Analysis of chimeric embryos implicates the requirement of Dkk1 in anterior axial mesendoderm but not in anterior visceral endoderm for head induction. In addition, mutant embryos show duplications and fusions of limb digits. Characterization of the limb phenotype strongly suggests a role for Dkk1 both in cell proliferation and in programmed cell death. Our data provide direct genetic evidence for the requirement of secreted Wnt antagonists during embryonic patterning and implicate Dkk1 as an essential inducer during anterior specification as well as a regulator during distal limb patterning.

T cell development in mice that lack the zeta chain of the T cell antigen receptor complex.

The zeta subunit of the T cell antigen receptor complex is required for targeting nascent receptor complexes to the cell surface and for receptor-mediated signal transduction. To examine the significance of the zeta subunit in T cell development, mice deficient for zeta expression were generated by gene targeting. These zeta-/- mice had few CD4+CD8+ thymocytes, and the generation of CD4+ and CD8+ single positive T cells was impaired but not completely abrogated. Peripheral T cells were present but were unusual in that they expressed small amounts of CD5 and few T cell receptors. Thus, zeta chain expression influences thymocyte differentiation but is not absolutely required for the generation of single positive T cells.

Specification of pituitary cell lineages by the LIM homeobox gene Lhx3.

During pituitary organogenesis, the progressive differentiation of distinct pituitary-specific cell lineages from a common primordium involves a series of developmental decisions and inductive interactions. Targeted gene disruption in mice showed that Lhx3, a LIM homeobox gene expressed in the pituitary throughout development, is essential for differentiation and proliferation of pituitary cell lineages. In mice homozygous for the Lhx3 mutation, Rathke's pouch formed but failed to grow and differentiate; such mice lacked both the anterior and intermediate lobes of the pituitary. The determination of all pituitary cell lineages, except the corticotrophs, was affected, suggesting that a distinct, Lhx3-independent ontogenetic pathway exists for the initial specification of this lineage.

Effect of cage charges on multiphoton absorptions: first-principles study on metallofullerenes Sc(2)C(2)@C(68) and Sc(3)N@C(68).

A combined method of the time-dependent density functional theory (TDDFT) and sum-overstate (SOS) formula was implemented to model multiphoton absorption spectra, including two-photon absorption (2PA) and three-photon absorption (3PA), of Sc(2)C(2)@C(68) and Sc(3)N@C(68) endohedral metallofullerenes (EMFs). This method has been proved to be effective by comparisons between the calculated and experimental results of trans-4,4'-bis[diphenylamino]stilbene. It was found that the multiphoton absorption cross sections were larger for Sc(2)C(2)@C(68) than that of Sc(3)N@C(68). The electronic origin of multiphoton absorption has been identified with respect to the molecular orbitals involved in charge transfer process. It shows that the increase of pi-charges on the cage of C(68) results in a large multiphoton absorption cross section in EMFs.

A periodic density functional theory study on the effects of halides encapsulated in SiC nanotubes.

In this paper we present results of density functional theory calculations on the configurations, band structures, and optical properties of halides MCl (M=K,Ag) intercalated single-wall SiC nanotubes. The results show that the M-Cl distances perpendicular to the tube axis are slightly smaller than the ones parallel to the tube axis, which could be due to the axial strain of MCl. The electronic and optical properties of the resulting MCl@SiCNT composite are modified with respect to both the bulk halide and the empty nanotube. It is shown that AgCl affects the structures and properties of SiC nanotubes more significantly than KCl, and that the interaction between the nanotube and the encapsulated halide is stronger for narrower SiC nanotube. The AgCl encapsulation into SiCNTs results in band gap narrowing of AgCl@SiCNTs.

The benefits of psychological displacement in diary writing when using different pronouns.

This study examined a new emotional writing paradigm, that is PDDP. PDDP instructs participants to write diary in first-person pronoun first, and then narrate the same event from a different perspective using second-person pronoun. Finally, the participants write it again with third-person pronoun from yet another perspective. These three narrations were to be written in a consecutive sequential order. Results demonstrated that diary writers indeed benefited from features of PDDP. It also showed that highly anxious people received most long-term therapeutic effect from PDDP. We argue that PDDP enacts the needed mechanism to balance psychological distance prolonging and self-disclosure making in emotional writing.