[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.

[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.

[Experimental observation on the effect of bone marrow mesenchymal stem cells transplanting CXCR4 over gentamicin ototoxicity].

Objective:To observe the survival and migration ability of CXCR4-BMSCs in guinea pig cochlea with gentamycin induced sensorineural hearing loss, and to explore whether SDF-1/CXCR4 axis can mediate bone marrow mesenchymal stem cells (BMSCs) to cochlear homing.Method:BMSCs were isolated and extracted from guinea pigs. A bone marrow mesenchymal stem cell line with overexpression of CXCR4 was established. The animal model of sensorineural deafness was established by intraperitoneal injection of gentamicinï¼»100 mg/(kg·d)ï¼½in 50 healthy guinea pigs. The successful deafness animals were randomly divided into three groups(14 rats in each group): sterilizing water group, BMSCs transplantation group and CXCR4-BMSCs transplantation group.Auditory brainstem response(ABR) were performed at 2 weeks and 4 weeks respectively after the tansplantation through cochlear tympanic pathway. The directional homing of the implanted cells in the cochlea was traced by the frozen section fluorescence of the cochlear tissue.Result:The hearing thresholds of the three groups were (91.3±5.2),(90.7±4.8)and (90.9±5.6)dB (SPL) respectively. There was no significant difference among them(P>0.05). In sterile Water group, the hearing thresholds were(89.7±6.4)dB and (89.2±6.7)dB respectively when detected on 2 and 4 weeks after transplantation. There were no significant difference(P>0.05);In BMSCs group, the hearing thresholds were (88.6±5.3)dB(SPL) on 2 weeks and (78.4±7.3)dB(SPL) on 4 weeks after transplantation. In CXCR4-BMSCs group, the hearing thresholds were(75.3±7.8)dB(SPL) on 2 weeks and (62.1±8.4)dB(SPL) on 4 weeks after transplantation. The differences were statistically significant (PThe hearing threshold was (75.3±7.8)dB (SPL) at 2 weeks after operation. The hearing enhancement was about 15 dB, the hearing threshold was (62.1±8.4)dB(SPL) at 4 weeks, the difference was statistically significant(P<0.05).Fluorescence tracing showed that the number of CXCR4-BMSCs homing cells was significantly increased, and showed a cohort like arrangement.Conclusion:The SDF-1/CXCR4 axis plays an important role in the directional homing and differentiation of the cells into the cochlea, which can improve the hearing repair ability of guinea pigs induced by gentamicin induced sensorineural deafness.

[Progress in research of family-based cohort study on common chronic non-communicable diseases in rural population in northern China].

Family-based cohort study is a special type of study design, in which biological samples and environmental exposure information of the member in a family are collected and related follow up is conducted. Family-based cohort study can be applied to explore the effect of genetic factors, environmental factors, gene-gene interaction, and gene-environment interaction in the etiology of complex diseases. This paper summarizes the objectives, methods and results, as well as the opportunities and challenges of the family-based cohort study on common chronic non-communicable diseases in rural population in northern 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.

[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.

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.

Growth under elevated air temperature alters secondary metabolites in Robinia pseudoacacia L. seedlings in Cd- and Pb-contaminated soils.

Plant secondary metabolites play a pivotal role in growth regulation, antioxidant activity, pigment development, and other processes. As the global climate changes, increasing atmospheric temperatures and contamination of soil by heavy metals co-occur in natural ecosystems, which alters the pH of rhizosphere soil and influences the bioavailability and mobility of metals. Elevated temperatures in combination with heavy metals are expected to affect plant secondary metabolites, but this issue has not been extensively examined. Here, we investigated secondary metabolites in Robiniapseudoacacia seedlings exposed to elevated temperatures using a passive warming device in combination with Cd- and Pb-contaminated soils. Heavy metals significantly stimulated the accumulation of saponins, phenolic compounds, and flavonoids in leaves and stems; alkaloid compounds increased in leaves and decreased in stems, and condensed tannins fluctuated. Elevated temperatures, alone and in combination with Cd and Pb, caused increases in secondary metabolites in the plant tissues. Phenolic compounds showed the greatest changes among the secondary metabolites and significant interactive effects of temperature and metals were observed. These results suggest that slightly elevated temperature could enhance protective and defense mechanisms of Robinia pseudoacacia seedlings exposed to heavy metals by stimulating the production of secondary metabolites.

The interaction of serum testosterone levels and androgen receptor CAG repeat polymorphism on the risk of erectile dysfunction in aging Taiwanese men.

Testosterone has been found to play important roles in men's sexual function. However, the effects of testosterone can be modulated by androgen receptor (AR) CAG repeat polymorphism. It could also contribute to the risk of erectile dysfunction (ED). The aim of this study is to evaluate the interaction of serum testosterone levels and AR CAG repeat polymorphism on the risk of ED in aging Taiwanese men. This cross-sectional data of Taiwanese men older than 40 years were collected from a free health screening held between August 2010 and August 2011 in Kaohsiung city, Taiwan. All participants completed a health questionnaires included five-item version of the International Index of Erectile Function (IIEF-5) and the International Prostate Symptoms Score, received a detailed physical examination and provided 20 cm3 whole blood samples for biochemical and genetic evaluation. The IIEF-5 was used to evaluate ED. Serum albumin, total testosterone (TT), and sex hormone-binding globulin levels were measured. Free testosterone level was calculated. AR gene CAG repeat polymorphism was determined by direct sequencing. Finally, 478 men with the mean age of 55.7 ± 4.8 years were included. When TT levels were above 330 ng/dL, the effect of testosterone level on erectile function seemed to reach a plateau and a significantly negative correlation between AR CAG repeat length and the score of IIEF-5 was found (r = -0.119, p = 0.034). After adjusting for other covariates, the longer AR CAG repeat length was still an independent risk factor for ED in subjects with TT above 330 ng/dL (p = 0.006), but not in TT of 330 ng/dL or below. In conclusion, both serum testosterone levels and AR CAG repeat polymorphism can influence erectile function concomitantly. In subjects with normal TT concentration, those with longer AR CAG repeat lengths have a higher risk of developing ED.

Organic anion transporting polypeptide-mediated transport of, and inhibition by, asunaprevir, an inhibitor of hepatitis C virus NS3 protease.

Asunaprevir (ASV), an investigational, highly protein-bound inhibitor of hepatitis C virus NS3 protease, shows considerable hepatic compartmentalization in animal models. Preclinical data showed ASV inhibition of human OATP1B1 (IC50 = 0.3 µM), OATP2B1 (0.27 µM), and, to a lesser extent OATP1B3 (3.0 µM), confirmed by modest (<2-fold) clinical elevations in rosuvastatin exposure with concomitant ASV. Although no significant OATP transport of ASV was observed in vitro at standard micromolar assay concentrations, clinical coadministration of ASV with a single dose of the OATP inhibitor rifampin gave large, variable increases in ASV plasma Cmax (21-fold mean) and AUCinf (15-fold mean), consistent with reduced hepatic uptake. In vitro reevaluation at therapeutically relevant low-nanomolar concentrations of unbound ASV showed active, saturable human hepatocyte uptake (Km = 0.685 µM) and rifampin-reversible transport by OATP1B1 and OATP2B1, but not OATP1B3. At therapeutically relevant concentrations, ASV is therefore a sensitive substrate for, and weak inhibitor of, human OATP1B1, 1B3 and 2B1.

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.

Impact of diabetes on diagnostic delay for pulmonary tuberculosis in Beijing.

SETTING: Delays in the diagnosis of pulmonary tuberculosis (PTB) increase the risk of transmission and severity of the disease. Little information is available on PTB patients with diabetes mellitus (DM). OBJECTIVES: To examine the impact of DM on delays in diagnosing PTB and the effect of diagnostic delay on the clinical presentation of PTB among patients in Beijing, China. DESIGN: In a cross-sectional study conducted in two PTB dispensaries of Beijing, all confirmed PTB patients were screened for DM. Data relating to diagnostic delay and clinical presentation of PTB were collected and analysed. RESULTS: Of 1126 PTB patients selected, 182 (16.2%) were identified as having DM. The median delay for PTB patients with DM (25 days) was significantly higher than that of PTB patients without DM (6 days). In a subgroup analysis, diagnostic delay was associated with smear positivity among PTB patients with DM (OR 3.10, 95%CI 1.66-5.76) and associated with smear positivity (OR 4.38, 95%CI 3.19-6.04), pulmonary cavities (OR 2.62, 95%CI 1.85-3.71) and more symptoms (OR 1.81, 95%CI 1.20-2.73) among PTB patients without DM. CONCLUSIONS: DM was associated with longer diagnostic delays, which in turn was associated with more serious clinical presentations of PTB. It is thus necessary to examine risk factors associated with diagnostic delay among PTB patients with and without DM.

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.