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Background: Intermittent pneumatic compression (IPC) and neuromuscular electrical stimulation can improve deep vein hemodynamics in the lower limbs. We developed a new, small and convenient, and easy to wear common peroneal nerve electrical stimulator (CPNES) and to investigate the effectiveness and safety of CPNES intervention on deep venous hemodynamics., Methods: Thirty healthy volunteers were recruited and randomly divided into group A and B. In group A, the hemodynamics of the left superficial femoral artery and the superficial femoral vein were measured after IPC compression, and then the CPNES was activated and the hemodynamics was measured again. In group B, the order of intervention was reversed., Results: In group A, the peak velocity, time average blood flow velocity (TAMV), and flow velocity of femoral vein after IPC and CPNES intervention were higher than these of the baseline (P < .05, respectively). No significant differences of these blood flow parameters were found between IPC and CPNES intervention (P > .05, respectively). In group B, these blood flow parameters of femoral vein after IPC and CPNES intervention were higher than these of the baseline (P < .05, respectively). No significant difference of these blood flow parameters (P > .05, respectively) were noted between IPC and CPNES intervention as well. No differential change of these flow velocity of femoral artery after IPC and CPNES intervention in group A or group B. The hemodynamics of superficial femoral arteries and veins after intervention in group A and B were similar (P > .05, respectively)., Conclusion: The effectiveness of CPNES intervention on the hemodynamics of the lower extremity is similar with that of IPC, increasing blood flow and may prevent venous thrombosis without adverse reaction., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

This study reported a family of MLH1 mutation-induced Muir-Torre syndrome (MTS) and evaluated it's clinical and genetic characteristics. A 51 year-old patient with extraorbital cystic sebaceous and colon adenocarcinoma diagnosed in November 2021 in Zhongshan Hospital of Xiamen University was included. The clinical data of the family were collected and a pedigree chart was drawn, which was in line with the Chinese Lynch syndrome diagnostic criteria and was a typical MTS family. NM&#95;000249.4:c.298C>T(p.R100*) of MLH1 gene in exon 3 was detected by whole exome sequencing and multiplex ligation dependent amplification, which is a pathogenic mutation. After the pathogenic mutation was identified, Sanger sequencing was performed on 4 direct members of the family for MLH1 gene, and 3 family members were found to have detected the mutation and included in MTS risk control. Until December 25 2023, follow-up showed the proband patients were not suffered from recurrence or new occurrence of skin or gastrointestinal tumors. The study reported a typical MTS family and found a possible pathogenic nonsense mutation in the MLH1 gene, which provides new evidence for the pathogenicity of this mutation.

Previously published studies have revealed the protective effect of puerarin against non-alcoholic steatohepatitis (NASH), but the definite mechanism of this effect still remains unclear. The present work was an attempt to assess the beneficial effects and the underlying mechanisms of puerarin on methionine-choline-deficient (MCD) diet-induced NASH in C57BL/6 mice by using a combination of metabonomics and 16S rRNA gene sequencing technology. Nuclear magnetic resonance (NMR)-based metabonomics showed significant hepatic and urinary metabolic phenotype changes between MCD-diet fed mice and the healthy controls. A total of eight and thirteen metabolites were identified as differential metabolites associated with NASH in liver tissue and urine of mice, respectively. The proposed pathways mainly included pyrimidine metabolism, one-carbon metabolism, amino acid metabolism, glycolysis, tricarboxylic acid (TCA) cycle and synthesis and degradation of ketone bodies. Furthermore, 16S rRNA gene sequencing analysis delineated remarkable variations in gut microbiota profiles in response to MCD diet in mice and forty differential bacterial taxa related to NASH were found between the control and model group. Puerarin could improve hepatic steatosis and inflammation in NASH mice via partially ameliorating metabolic disorders and rebalancing the gut flora. Specifically, puerarin could inhibit lipopolysaccharide (LPS)-producing genus Helicobacter, and promote butyrate-producing genus Roseburia. These findings offered novel insights into the in-depth understanding of the pathogenesis of NASH and provided further evidence for the potential use of puerarin as an anti-NASH agent., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Multiple measurements of nocturnal penile tumescence and rigidity (NPTR) are widely accepted as a method to differentiate psychogenic erectile dysfunction (ED) from organic ED. However, direct evidence remains limited regarding the first-night effect on NPTR measurement using the RigiScan. Here, we evaluated the first-night effect on the results of NPTR measurement to validate the necessity of NPTR measurement for two consecutive nights, particularly when abnormal first-night measurements are recorded in a laboratory setting. We retrospectively reviewed 105 patients with a complaint of ED, who underwent NPTR measurement using the RigiScan in the Department of Infertility and Sexual Medicine, the Third Affiliated Hospital of Sun Yat-sen University (Guangzhou, China), for two consecutive nights, during the period from November 2015 to May 2016. NPTR parameters were collected and analyzed. We found that more effective nocturnal erections were detected during the second night than during the first night (P <0.001). Twenty percent of all patients had no effective erection during the first night, but exhibited at least one effective erection during the second night. The negative predictive value of NPTR measurement during the first night was 43.2%; this was significantly lower than that on the second night (84.2%; P = 0.003). Most NPTR parameters were better on the second night than on the first night. The first-night effect might be greater among patients younger than 40 years of age. In conclusion, two consecutive nightly measurements of NPTR can avoid a false-abnormal result caused by the first-night effect; moreover, these measurements more accurately reflect erectile capacity, especially when the first-night record is abnormal in a laboratory setting., Competing Interests: None

Objective: This study aims to observe the curative effect of Huaiqihuang Granules adjuvant therapy on primary nephrotic syndrome (PNS)., Methods: A total of 112 children with PNS were randomly divided into three groups, and changes in serum inflammatory cytokines, interleukin, lymphocyte subsets and immunoglobulin were observed., Results: Before treatment, IL-18, TNF-α, CD8+ increased, while IL-10, CD4+, NK cells, IgA, IgG and Foxp3+Treg cells decreased. After Huaiqihuang Granules treatment, IL-18, TNF-α, CD8+ decreased, while IL-10, CD4+, NK cells, IgA, IgG and Foxp3+Treg cells increased., Conclusion: Functions of cell immunity and humoral immunity in PNS patients before treatment were suppressed and disordered. Huaiqihuang granules can play a role in immunoregulation, with slight side reactions., Competing Interests: Conflict of interest: Authors state no conflict of interest., (© 2019 Ping Zhou et al., published by De Gruyter.)

Competing Interests: None

Objective: To investigate effect and mechanism of miR-214 in fludarabine resistance of chronic lympho-cytic leukemia (CLL)., Methods: A total of 10 patients with CLL resistante to fludarabine (Flu) and 10 healthy persons admitted to Hematology Department of our hospital in August 2014 - July 2018 were selected. Expression level of miR-214 in mononuclear cells in patients with CLL and healthy persons were determined by RT-PCR. Primary CLL cells from patients with CLL were divided into normal control group (control group), negative control group (miR-214-NC group) and viral transinfection group (miR-214-ASO group). After 24 h-transfection, CLL cells were cultured with different con-centration of Flu for 48 h, then the cell proliferation and apoptosis were detected, and the levels of down-stream genes and proteins releted with PTEN and PI3K/AKT signialing pathway were determined., Results: The expression level of miR-214 in mononuclear cells of CLL patients significantly increased in comparison with healthy persons(P<0.05); the expression level of miR-214 in miR-214-ASO group significantly decreased (P<0.05); Absorbance in control group at Flu concentration of 3, 10 and 30 μmol/L was significantly decreased (P<0.05). Apoptosis rate in miR-214-ASO group at Flu concentration of 10 mmol/L significantly increased (P<0.05). At Flu concentration of 10 mmol/L, mRNA levels PTEN and BAD in miR-214-ASO group significantly increased (P<0.05), but mRNA levels of MDM2 and NF-κB significantly decreased (P<0.05). At Flu concentration of 10 mmol/L, protein levels of PTEN and p-BAD in miR-214-ASO group significantly increased (P<0.05), but protein levels of MDM2 and NF-κB significantly decreased (P<0.05)., Conclusion: Inhibition of miR-214 can enhance the sensitivity of drug-resistant CLL cells to fludarabine, which may be raleted with the promotion of cell apotosis and regulation of down-stream molecules expression of PTEN/AKT signaling pathway.

The relative concentration index (RCI) and the absolute concentration index (ACI) have been widely used for monitoring health disparities with ranked health determinants. The RCI has been extended to allow value judgments about inequality aversion by Pereira in 1998 and by Wagstaff in 2002. Previous studies of the extended RCI have focused on survey sample data. This paper adapts the extended RCI for use with directly standardized rates (DSRs) calculated from population-based surveillance data. A Taylor series linearization (TL)-based variance estimator is developed and evaluated using simulations. A simulation-based Monte Carlo (MC) variance estimator is also evaluated as a comparison. Following Wagstaff's approach in 1991, we extend the ACI for use with DSRs. In all simulations, both the TL and MC methods produce valid variance estimates. The TL variance estimator has a simple, closed form that is attractive to users without sophisticated programming skills. The TL and MC estimators have been incorporated into a beta version of the National Cancer Institute's Health Disparities Calculator, a free statistical software tool that enables the estimation of 11 commonly used summary measures of health disparities for DSRs., (Published 2018. This article is a U.S. Government work and is in the public domain in the USA.)

Background: The 8th American Joint Committee on Cancer tumor-node-metastasis (AJCC-TNM) staging system is based on a few retrospective single-center studies. We aimed to test the prognostic validity of the staging system and to determine whether a modified clinicopathological tumor staging system that includes lymphovascular embolization could increase the accuracy of prognostic prediction for patients with stage T2-3 penile cancer., Methods: A training cohort of 411 patients who were treated at 2 centers in China and Brazil between 2000 and 2015 were staged according to the 8th AJCC-TNM staging system. The internal validation was analyzed by bootstrap-corrected C-indexes (resampled 1000 times). Data from 436 patients who were treated at 15 centers over four continents were used for external validation., Results: A survivorship overlap was observed between T2 and T3 patients (P = 0.587) classified according to the 8th AJCC-TNM staging system. Lymphovascular embolization was a significant prognostic factor for metastasis and survival (all P < 0.001). Based on the multivariate analysis, only lymphovascular embolization showed a significant influence on cancer-specific survival (CSS) (hazard ratio = 1.587, 95% confidence interval = 1.253-2.011; P = 0.001). T2 and T3 patients with lymphovascular embolization showed significantly shorter CSS than did those without lymphovascular embolization (P < 0.001). Therefore, a modified clinicopathological staging system was proposed, with the T2 and T3 categories of the 8th AJCC-TNM staging system being subdivided into two new categories as follows: t2 tumors invade the corpus spongiosum and/or corpora cavernosa and/or urethra without lymphovascular invasion, and t3 tumors invade the corpus spongiosum and/or corpora cavernosa and/or urethra with lymphovascular invasion. The modified staging system involving lymphovascular embolization showed improved prognostic stratification with significant differences in CSS among all categories (all P < 0.005) and exhibited higher accuracy in predicting patient prognoses than did the 8th AJCC-TNM staging system (C-index, 0.739 vs. 0.696). These results were confirmed in the external validation cohort., Conclusions: T2-3 penile cancers are heterogeneous, and a modified clinicopathological staging system that incorporates lymphovascular embolization may better predict the prognosis of patients with penile cancer than does the 8th AJCC-TNM staging system. Trial registration This study was retrospectively registered on Chinese Clinical Trail Registry: ChiCTR16008041 (2016-03-02). http://www.chictr.org.cn.

Low-intensity extracorporeal shock wave therapy (LI-ESWT) is a novel treatment for erectile dysfunction (ED). Its ability to improve erectile function has been shown in patients with vasculogenic ED by many randomized-controlled trials against sham procedures. However, the role of LI-ESWT in ED caused by radical prostatectomy (RP) is still questionable because this type of ED was excluded from nearly all clinical studies; it has been investigated in only a few small single-arm trials. This review summarizes preclinical studies on mechanisms of action of LI-ESWT for ED and neurological diseases to explore the potential of this treatment for nerve-impaired ED after RP.

Aim: The role of low-intensity extracorporeal shock wave therapy (LI-ESWT) in erectile dysfunction (ED) is not clearly determined. The purpose of this study is to investigate the short-term efficacy and safety of LI-ESWT for ED patients., Materials and Methods: Relevant studies were searched in Medline, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), WANFANG and VIP databases. Effective rate in terms of International Index of Erectile Function-Erectile Function Domain (IIEF-EF) and Erectile Hardness Score (EHS) at about 1month after LI-ESWT was extracted from eligible studies for meta-analysis to calculate risk ratio (RR) of effective treatment in ED patients treated by LI-ESWT compared to those receiving sham-treatment., Results: Overall fifteen studies were included in the review, of which four randomized controlled trials (RCTs) were for meta-analysis. Effective treatment was 8.31 [95% confidence interval (CI): 3.88-17.78] times more effective in the LI-ESWT group (n=176) than in the sham-treatment group (n=101) at about 1 month after the intervention in terms of EHS, while it was 2.50 (95% CI: 0.74-8.45) times more in the treatment group (n=121) than in the control group (n=89) in terms of IIEF-EF. Nine-week protocol with energy density of 0.09mJ/mm2 and 1500 pluses seemed to have better therapeutic effect than five-week protocol. No significant adverse event was reported., Conclusion: LI-ESWT, as a noninvasive treatment, has potential short-term therapeutic effect on patients with organic ED irrespective of sensitivity to PDE5is. Owing to the limited number and quality of the studies, more large-scale, well-designed and long-term follow-up time studies are needed to confirm our analysis., Competing Interests: Conflict of interest: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Background: Current guidelines recommend pelvic lymphadenectomy (PLND) for patients with pelvic lymph node metastasis and special state. However, these data and recommendations do not distinguish the role of PLND in different patient groups and confirm the final benefits. The aim of this study was to confirm the efficacy of pelvic lymphadenectomy (PLND) for the different groups of patients., Methods: Data obtained from 7 centers were retrospectively analyzed. Of the patients, 190 pN2-3 penile carcinoma patients confirmed by bilateral inguinal lymph node excision were included in this study. Sixty-nine and 121 of these patients did and did not undergo bilateral PLND, respectively. The baseline differences from the patients were matched by propensity score analysis., Results: In this study, the Kaplan-Meier estimated disease-specific survival (DSS) was not significantly different between the PLND and no-PLND groups (P = 0.796). According to the propensity score matching for T stage, N stage, grade, adjuvant therapies, and lymph node stage (number of inguinal lymph node metastasis and extranodal extension), 48 patients were selected for each group. Among the pN2 patients, the PLND group showed higher DSS rates than the no-surgery group (P = 0.030). However, even after matching, survival did not differ between the PLND and no-PLND patients among all patients (P = 0.609) and pN3 patients (P = 0.417) with comparable DSS., Conclusion: Bilateral PLND may improve survival in pN2 patients. Men with pN3 may not benefit from bilateral PLND.

Primary epididymal adenocarcinoma (PEA) is exceedingly rare. Only 22 cases had been published worldwide by 2008; nearly 80% of these cases were reported before 2007. In order to investigate the current clinical status of PEA, we search for relevant literatures with "epididymis and adenocarcinoma" and "epididymal and adenocarcinoma" as keywords published between January 1997 and November 2017 in PubMed. As a result, 17 cases are identified. We review these cases and summarize new and important perspectives about the clinicopathological characteristics, diagnosis, treatment, and prognosis of PEA in the present review.

Purpose: More literatures regarding radiocolloid-based dynamic sentinel lymph node biopsy (DSNB) in penile cancer with clinically negative groin (cN0) have been published since previous meta-analysis in 2012. This updated meta-analysis was to assess the accuracy of the procedure in penile cancer with cN0 disease and explore its relative factors on the basis of current evidences., Materials and Methods: We performed a review of PubMed, Ovid/Embase, and the Cochrane Library in March 2016 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. Study quality was evaluated by the use of the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). A random effects model was used for statistical pooling. Publication bias was evaluated by the use of funnel plot and Egger's test. Meta-regression, subgroup and sensitivity analysis were conducted to explore the sources of heterogeneity., Results: A total of 27 articles were included. Two articles had two different cohorts and each cohort was considered a separate study. Overall 29 studies were used for sensitivity and negative predictive value (NPV) meta-analysis. The pooled sensitivity and NPV was 88 % (95 % CI 84-90 %) and 99 % (98-99 %), respectively. Meta-regression and subgroup analysis revealed that the use of preoperative ultrasonic scan (USS) ± fine-needle aspiration cytology (FNAC), surgical exploration of wound for suspicious lymph nodes (LN), immunohistochemistry (IHC) and extensive experience were significantly associated with the improved sensitivity of DSNB., Conclusions: Radiocolloid-based DSNB is a promising staging modality to detect inguinal micrometastasis in penile cancer without clinically positive inguinal LN. Preoperative USS ± FNAC and surgical exploration are effective supplements to exclude potentially clinical involvement, and IHC makes the diagnosis of occult metastasis in SLN more likely. The multidisciplinary and multistep procedure should be performed by skilled teams in specialized centers.

Objective: To determine the clinical effect of Friend-Ⅰ External Physical Vibration Lithecbole (EPVL) by Meta-analysis. Methods: Pubmed, Embase, Medline, Cochrane Library, Chinese National Knowledge Infrastructure were searched for clinical trials comparing EPVL with the conventional treatment. The quality of included studies was assessed and Meta-analysis was conducted by Review Manager 5.3 software. Results: Five randomized or Quasi-randomized controlled trials met the inclusion criteria. The first day stone expulsion rate of EPVL group was superior to the control group ( OR =4.95, 95% CI : 3.35-7.32, P <0.000 01). Both one-week ( OR =3.13, 95% CI : 1.95-5.04, P <0.000 01) and two-week stone free rate ( OR =4.50, 95% CI : 2.02-10.00, P =0.000 2) were statistically higher in the EPVL group than that in the control group. No severe adverse event occurred during the follow-up. Conclusions: Our study suggested that EPVL could be the effective treatment for upper urinary tract residual stone. However, more high quality randomized controlled trials are needed to better affirm this.

To elucidate the intervention effects of Jiaotai pills(JTP) on p-chlorophenylalanine (PCPA)-induced insomnia in rats and its underlying mechanism, the insomnia model was established by single intraperitoneal injection with PCPA in rats. The locomotor activity of rats was observed, and the levels of nerve growth factor(NGF) in hypothalamus, hippocampus, prefrontal cortex and serum of rats were determined by using ELISA. Moreover, a proton nuclear magnetic resonance(¹H-NMR)-based metabonomic approach was developed to profile insomnia-related metabolites in rat serum and hippocampus and analyze the intervention effects of JTP on changes in underlying biomarkers related to locomotor activity, NGF and insomnia. According to the results, JTP could significantly suppress the locomotor activity of insomnia rats, and increase the NGF levels in hypothalamus, hippocampus, prefrontal cortex and serum of rats with insomnia. The disturbed metabolic state associated with PCPA-induced insomnia in rat serum and hippocampus could be intervened by JTP. Meanwhile, six and five potential biomarkers related to insomnia in rat serum and hippocampus were reversed by administration of JTP. In conclusion, the current study demonstrated that JTP had protective effects against PCPA-induced insomnia in rats, which was probably correlated with regulation of NGF level and metabolism of amino acids, lipids and choline., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

Background: Recently, calreticulin (CALR) gene mutations have been identified in patients with essential thrombocythemia (ET). A high-frequency of ET cases without Janus kinase 2 (JAK2) mutations contain CALR mutations and exhibit clinical characteristics different from those with mutant JAK2. Thus, we investigated the frequency and clinical features of Chinese patients of Han ethnicity with CALR mutations in ET., Methods: We recruited 310 Chinese patients of Han ethnicity with ET to analyze states of CALR, JAK2V617F, and MPLW515 mutations by polymerase chain reaction and direct sequencing. We analyzed the relationship between the mutations and clinical features., Results: CALR, JAK2V617F, and MPLW515 mutations were detected in 30% (n = 92), 48% (n = 149), and 1% (n = 4) of patients with ET, respectively. The mutation types of CALR involved deletion and insertion of base pairs. Most of them were Type 1 (52-bp deletion) and Type 2 (5-bp insertion, TTGTC) mutations, leading to del367fs46 and ins385fs47, respectively. The three mutations were exclusive. Clinically, patients with mutated CALR had a lower hemoglobin level, lower white blood cell (WBC) count, and higher platelet count compared to those with mutated JAK2 (P < 0.05). Furthermore, a significant difference was found in WBCs between wild-type patients (triple negative for JAK2, MPL, and CALR mutations) and patients with JAK2 mutations. Patients with CALR mutations predominantly clustered into low or intermediate groups according to the International Prognostic Score of thrombosis for ET (P < 0.05)., Conclusions: CALR mutations were frequent in Chinese patients with ET, especially in those without JAK2 or MPL mutations. Compared with JAK2 mutant ET, CALR mutant ET showed a different clinical manifestation and an unfavorable prognosis. Thus, CALR is a potentially valuable diagnostic marker and therapeutic target in ET.

In order to study the persistence of a combined amendment (LS, limestone+sepiolite) for remedying paddy soil polluted with the heavy metals Pb and Cd, a three-year in-situ experiment was conducted in a paddy soil near a mining area in southern Hunan, China. LS was applied at rates of 0, 2, 4, and 8g/kg (w/w); rice was subsequently planted for the three consecutive years of 2012 (first season), 2013 (second season), and 2014 (third season). Experimental results indicated that LS significantly increased soil pH values for all three seasons, and the enhancement ranked as follows: first season>second season>third season. Under the experimental conditions, the effect of LS on decreasing exchangeable concentrations of soil Pb and Cd was as follows: first season (97.6-99.8% for Pb and 88.3-98.9% for Cd)>second season (80.7-97.7% for Pb and 28.3-88.0% for Cd)>third season (32.6-97.7% for Pb and 8.3-71.4% for Cd); the effect of LS on reducing Pb concentrations in brown rice was: first season (73.5-81.2%)>third season (29.6-68.1%)>second season (0-9.7%), and that for reducing Cd concentrations in brown rice was third season (72.7-81.0%)>first season (56.1-66.8%)>second season (20.9-32.3%). For all three seasons, the effect of LS on reducing Cd content in brown rice was better than that for Pb. The highest translocation factors for Pb and Cd were from rice straw to husk, implying that the husk of rice plants was the main organ in which heavy metals accumulated. The effect of LS for decreasing soil exchangeable Cd content was relatively persistent, but that for Pb gradually decreased with time, implying that LS was more suitable for the long-term remediation of Cd-polluted soil than Pb-polluted soil., (Copyright © 2016 Elsevier Inc. All rights reserved.)

A three-year in-situ experiment was conducted in a paddy soil near a mining area in southern Hunan in order to study the persistence of combined amendment of limestone+sepiolite (marked as LS) stabilizing Pb, Cd, Cu and Zn in polluted paddy soil. LS with ratios of 0, 2, 4, and 8 g·kg -1 was applied once to the paddy soil, and rice was subsequently planted for three consecutive years of 2012 (first season), 2013 (second season), and 2014 (third season). The experimental results indicated that:①LS significantly increased soil pH values for all three seasons, and the enhancement ranked as follows:first season > second season > third season. ② LS obviously decreased the exchangeable contents of soil Pb, Cd and Zn for all three seasons, and the decreasing magnitude of exchangeable contents of soil heavy metals was 32.6%-97.7% for Pb, 8.3%-71.4% for Cd, and 10.9%-83.5% for Zn, respectively, in the third season; however, there was no significant decrease for Cu. The effects of LS decreasing exchangeable contents of soil heavy metals in three seasons followed the order of Pb > Zn > Cd > Cu. ③ LS decreased contents of Pb and Cd in brown rice in the third season by 26.7%-66.7% and 59.1%-80.3%, respectively, and the reduction trend increased with increasing LS application. Cu and Zn contents in brown rice did not decrease effectively. The effect of LS reducing contents of Pb, Cd, Cu and Zn in brown rice followed the order of Pb > Cd > Cu > Zn for the first season and the second season, but Cd > Pb > Zn > Cu for the third season. For all three seasons, the total effect of LS reducing heavy metal contents in brown rice followed the order of Pb > Cd > Cu > Zn. ④ The effect of LS stabilizing soil Pb and Cd emerged gradually with time. Therefore, LS was suitable for remedying soil polluted with Pb and Cd for a relatively long time because of its persistence.

Low-intensity extracorporeal shockwave therapy (LI-ESWT) is a novel treatment for erectile dysfunction (ED). With the property of angiogenesis, LI-ESWT acts on vasculogenic ED by improving penile hemodynamics and endothelial function. LI-ESWT is proved to be safe and effective in the treatment of vasculogenic ED in various prospective clinical studies, including randomized, double-blind, and sham-controlled trails. With more multi-centered larger-sample randomized controlled trials, LI-ESWT will play a valuable role in the treatment of ED.

Previously published reports have revealed the antidepressant-like effects of icariin in a chronic mild stress model of depression and in a social defeat stress model in mice. However, the therapeutic effect of icariin in an animal model of glucocorticoid-induced depression remains unclear. This study aimed to investigate antidepressant-like effect and the possible mechanisms of icariin in a rat model of corticosterone (CORT)-induced depression by using a combination of behavioral and biochemical assessments and NMR-based metabonomics. The depression model was established by subcutaneous injections of CORT for 21 consecutive days in rats, as evidenced by reduced sucrose intake and hippocampal brain-derived neurotrophic factor (BDNF) levels, together with an increase in immobility time in a forced swim test (FST). Icariin significantly increased sucrose intake and hippocampal BDNF level and decreased the immobility time in FST in CORT-induced depressive rats, suggesting its potent antidepressant activity. Moreover, metabonomic analysis identified eight, five and three potential biomarkers associated with depression in serum, urine and brain tissue extract, respectively. These biomarkers are primarily involved in energy metabolism, lipid metabolism, amino acid metabolism and gut microbe metabolism. Icariin reversed the pathological process of CORT-induced depression, partially via regulation of the disturbed metabolic pathways. These results provide important mechanistic insights into the protective effects of icariin against CORT-induced depression and metabolic dysfunction., (Copyright © 2016 Elsevier B.V. All rights reserved.)

In the present study, calcium carbonate (CaCO3) was applied to Cd-contaminated soil at rates of 0, 0.5 and 1.0 g kg(-1). The effect of CaCO3 on soil pH, organic matter, available Cd, exchangeable Cd and level of major nutrients in a tobacco field and on accumulation of various elements in tobacco plants was determined. The results showed that CaCO3 application significantly increased the pH level, available P and exchangeable Ca but decreased organic matter, available Cd, exchangeable Cd, available heavy metals (Fe, Mn, Zn and Cu) and available K in soil. Additionally, CaCO3 application substantially reduced Cd accumulation in tobacco roots, stems, upper leaves, middle leaves and lower leaves, with maximum decrease of 22.3%, 32.1%, 24.5%, 22.0% and 18.2%, respectively. There were large increase in total Ca and slight increases in total N and K but decrease to varying degrees in total Fe, Cu and Zn due to CaCO3 application. CaCO3 had little effect on total P and Mn levels in tobacco leaves.

Objective: To observe metabolomic changes in urine of chronic superficial gastritis (CSG) patients with Pi-qi deficiency syndrome (PQDS) or Pi-Wei dampness-heat syndrome (PWDHS), thereby providing scientific evidence for syndrome typing of them., Methods: Urine samples were collected from CSG patients with PQDS/PWDHS and healthy volunteers, 10 in each group. Proton nuclear magnetic resonance spectroscopy (1H-NMR) based metabonomic analysis was performed on urine samples. Contents of related biomarkers were analyzed by principal component analysis (PCA), partial least square discriminant analysis (PLS-DA), and urivariate statistical analysis., Results: PLS-DA analysis showed that metabolites among CSG patients with PQDS/PWDHS and healthy volunteers could be mutually distinguished. Seven differentially identified metabolites were screened from urines of CSG patients with PQDS and healthy volunteers included glutamate, methionine, α-oxoglutarate, dimethylglycine, creatinine, taurine, and glucose. Four differentially identified metabolites were screened from urines of CSG patients with PWDHS and healthy volunteers included 2-hydroxybutyric acid, trimethylamine oxide, taurine, and hippuric acid. Eleven differentially identified metabolites were screened from urines of CSG patients with PQDS and PWDHS included fucose, β-hydroxybutyric acid, alanine, glutamate, methionine, succinic acid, citric acid, creatinine, glucose, hippuric acid, and lactic acid., Conclusion: The metabolic differences of CSG patients PQDS and PWDHS mainly manifested in glycometabolism, lipid metabolism, and amino acids catabolism, and 1H-NMR based metabonomics may be used in classified study of Chinese medical syndrome typing.

Background: The available evidence suggests that simvastatin plays a beneficial role in lung injury. In addition, statins have been shown to inhibit the activity of inducible nitric oxide synthase (iNOS). The aim of the present study was to investigate the effects of simvastatin on iNOS expression based on a lipopolysaccharide (LPS)-induced septic rat model., Methods: Thirty-six rats were randomly divided into 3 groups (control group, sepsis group and simvastatin group). A rat model of sepsis was established with LPS. The simvastatin group was pre-treated with simvastatin, whereas the control and sepsis groups were treated with saline before LPS treatment. LPS was injected into the rats in the simvastatin and sepsis groups, while as a negative control, the control group received saline alone. The oxygenation index, expression levels of iNOS and IL-6, and pathological integral of lung injury were analyzed to evaluate the effect of simvastatin on septic rats., Results: Compared with the septic group, significant decreases in the oxygenation index and expression level of iNOS were observed in the simvastatin group. Furthermore, simvastatin treatment resulted in a significant decrease in iNOS levels and the pathological integral of lung injury score in septic rats., Conclusion: Simvastatin can relieve acute lung injury induced by sepsis in rats. Decreasing iNOS levels may contribute to the protective role of simvastatin in lung injury.

Puerarin possesses a wide spectrum of biological activities including ameliorating effects on blood stasis, but the definite mechanism of this effect is still not known. In this study, a (1)H NMR-based plasma and urinary metabonomic approach was applied to comprehensively and holistically investigate the therapeutic effects of puerarin on blood stasis and its underlying mechanisms. Puerarin was injected intraperitoneally once daily for consecutive 7 days. The blood stasis rat model was established by placing the rats in ice-cold water during the time interval between two injections of adrenaline. With pattern recognition analysis, a clear separation of blood stasis model group and healthy control group was achieved and puerarin pretreatment group was located much closer to the control group than the model group, which was consistent with results of hemorheology studies. 15 and 10 potential biomarkers associated with blood stasis in plasma and urine, respectively, which were mainly involved in energy metabolism, lipid and membrane metabolisms, amino acid metabolism and gut microbiota metabolism, were identified. Puerarin could prevent blood stasis through partially regulating the disturbed metabolic pathways. This work highlights that metabonomics is a valuable tool for studying the essence of blood stasis as well as evaluating the efficacy of the corresponding drug treatment., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

The purpose of this study was to investigate the significance of polymorphisms in the CD20 gene in patients with diffuse large B-cell lymphoma (DLBCL). We sequenced exons 3-8 in 160 patients with de novo DLBCL and detected the expression of CD20 via immunohistochemistry. We found two single nucleotide polymorphisms (SNPs): rs17155019 in the 5' untranslated region and rs2070770 (ILE72/ILE72) in exon 4. There was no significant difference in genotype frequencies of SNPs between patients and controls (p = 0.855 and 0.251, respectively). In patients who received rituximab-containing chemotherapies, the T allele of rs2070770 was significantly associated with superior overall survival (OS) (p = 0.029) and progression-free survival (p = 0.045). Analogously, in patients who did not receive rituximab, the T allele of rs2070770 (p = 0.047) was also significantly associated with longer OS. In conclusion, SNPs of CD20 were not high risk factors of DLBCL, but the T allele of rs2070770 was a potential indicator of superior survival.

We previous found the expression level of PTEN was low in the chronic lymphocytic leukemia (CLL) patients. To assess the pathogenic contribution of the low expression of PTEN, we determined PTEN-regulating miRNA interference, PTEN promoter methylation and PTEN gene mutation condition in CLL. One hundred and fifty-four previously untreated CLL patients and 200 cases of healthy controls were sequenced in exons 5-9 of PTEN. None of single nucleotide polymorphism site or mutation was detected in the coding sequences of those exons. Methylation of PTEN promoter was found in one (1.33%) of the 75 patients with CLL, but none of the 25 age-matched control subjects. We found that PTEN was a potential target of miR-26a and miR-214, which had been confirmed following dual-luciferase reporter assays, reverse transcription polymerase chain reaction and Western blotting. High expression of miR-26a was associated with advanced Binet stage (P=0.012), p53 aberrations (P=0.014) and inferior time to first treatment (P=0.038), and high expression of miR-214 was only associated with p53 aberrations (P=0.041). Inhibition of miR-26a or miR-214 could induce more apoptosis in primary cultured CLL cells. These findings support miR-26a and miR-214 down-regulate expression of PTEN in CLL, but not PTEN mutation or promoter methylation.

Numerous studies of associations between dampness and respiratory diseases have been conducted, but their implications remain inconclusive. In this study of 13,335 parent-reported questionnaires (response rate: 85.3%), we analyzed associations between home dampness and asthma and related symptoms in 4- to 6-year-old children in a cross-sectional study of Shanghai. Indicators of home dampness were strongly and significantly associated with dry cough, wheeze, and rhinitis symptoms. In the current residence, children with visible mold spots (VMS) exposure had 32% higher risk of asthma (adjusted OR, 95% CI: 1.32, 1.07-1.64); damp clothing and/or bedding (frequently) was strongly associated with dry cough (1.78, 1.37-2.30); condensation on windows was strongly associated with hay fever (1.60, 1.27-2.01). In the early-life residence, VMS or damp stains (frequently) were strongly associated with dry cough (2.20, 1.55-3.11) and rhinitis ever (1.57, 1.11-2.21). Associations between dampness and diseases among children with or without family history of atopy were similar. The total number of dampness indicators had strong dose-response relationships with investigated health outcomes. Actions, including opening windows of the child's room at night and cleaning the child's room frequently, could potentially mitigate 25% of home VMS, thereby preventing more than 1.5% of attributable risk of the studied symptoms., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To investigate the value of removed lymph node (LN) count and LN density (LND) for predicting disease-specific survival (DSS) rate following radical lymphadenectomy in patients with penile cancer., Methods: We retrieved data from 146 patients who were surgically treated between 2002 and 2012. receiver-operating characteristic curve analysis was used to calculate the optimal cutoff value of LN count and LND for predicting DSS rate. LND was analyzed as a categorical variable by grouping patients with pN+tumors into 2 categories. Multivariate Cox regression analysis was used to test the effect of various variables on DSS rate based on collinearity in various models., Results: Median follow-up was 42 months. Overall, 75 patients (51.4%) had pN0 disease, and 71 patients (48.6%) had pN+disease. The optimal cutoff value of LN count and LND were 16% and 16%, respectively. Among patients with pN0 tumors, the number of LNs removed (≥16 LNs) was an independent significant predictor of DSS rate in univariate and multivariate analyses (all P<0.05). Stratifying pN+ patients as above versus below the LND threshold demonstrated significant differences in 5-year DSS: 81.2% versus 24.4% (P < 0.001). In multivariate models including known prognostic factors, LND was a statistically significant independent predictor of DSS rate (hazard ratio = 4.31 and 3.96 for above vs. below the LND threshold, respectively)., Conclusions: The removal of at least 16 LNs was associated with a significantly longer DSS rate in patients with pN0 penile cancer. Additionally, an LND above 16% is an independent predictor of DSS rate in patients with pN+tumors. Further independent validation is required to determine the clinical usefulness of LN count and LND in this patient population., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objectives: To determine whether SOX11 is a diagnostic marker of mantle cell lymphoma (MCL)., Methods: We analyzed SOX11 expression in 349 B-cell non-Hodgkin lymphomas (B-NHLs) via immunohistochemistry., Results: Nuclear staining of SOX11 was observed in 54 (93.1%) of 58 MCLs. We noticed that SOX11 protein was also expressed on the nuclei in 8 (21.6%) of 37 B-lymphoblastic lymphomas, 45 (32.6%) of 138 diffuse large B-cell lymphomas, 15 (44.1%) of 34 follicular lymphomas, 8 (30.8%) of 26 Burkitt lymphomas, 2 (10.0%) of 20 chronic lymphocytic leukemia/small cell lymphomas, and 3 (18.8%) of 16 marginal zone lymphomas., Conclusions: Although the positive rate of SOX11 expression in MCL was significantly higher than other B-NHLs (P < .001), polyclonal antibody targeting SOX11 is not able to identify MCL from B-NHLs because the nuclear staining of SOX11 was widely positive in B-NHLs.

The purpose of this study was to explore the characteristics and functions of BH3-only proteins Puma, Noxa and Bim in the prognosis, therapy and drug resistance of chronic lymphocytic leukemia (CLL). Puma, Noxa and Bim mRNAs were evaluated by real-time quantitative reverse transcriptase-polymerase chain reaction, and correlations between their expression levels and CLL prognostic markers were analyzed. Primary CLL samples were treated in vitro with fludarabine to investigate the role of Puma, Noxa and Bim in the response to chemotherapeutic drugs which act through activation of the p53 pathway. We found that a low expression level of Puma was associated with some markers of poor prognosis. However, the level of Noxa or Bim was not different in patients with CLL with variant clinical features and prognostic factors. Puma expression was up-regulated after fludarabine treatment in primary CLL cells, but there was no significant difference for Noxa and Bim. Up-regulation of Puma occurred only in CLL cells with functional p53. CLL cells with p53 abnormalities were deficient in the activation of Puma by chemotherapeutics. These results suggest that a lack of Puma induction may contribute to the development of resistance to anticancer agents in CLL.

To investigate the intervention effects of Morinda officinalis How. on 'Kidney-yang deficiency syndrome' induced by hydrocortisone in rats, the metabolic profiles of rat urine were characterized using proton nuclear magnetic resonance and principal component analysis (PCA) was applied to study the trajectory of urinary metabolic phenotype of rats with 'Kidney-yang deficiency syndrome' under administration of M. officinalis at different time points. Meanwhile, the intervention effects of M. officinalis on urinary metabolic potential biomarkers associated with 'Kidney-yang deficiency syndrome' were also discussed. The experimental results showed that in accordance to the increased time of administration, an obvious tendency was observed that clustering of the treatment group moved gradually closed to that of the control group. Eight potential biomarkers including citrate, succinate, alpha-ketoglutarate, lactate, betaine, sarcosine, alanine and taurine were definitely up- or down-regulated. In conclusion, the effectiveness of M. oficinalis on 'Kidney-yang deficiency syndrome' is proved using the established metabonomic method and the regulated metabolic pathways involve energy metabolism, transmethylation and transportation of amine. Meanwhile, the administration of M. officinalis can alleviate the kidney impairment induced by 'Kidney-yang deficiency syndrome'.

Objective: To investigate local groin recurrence and morbidity associated with fascia lata preservation during inguinal lymphadenectomy (LAD) for penile carcinoma., Methods: Between January 2002 and December 2011, 201 inguinal dissections with preservation of the fascia lata were performed in 104 patients with clinical disease staged at ≤N2. The dissection boundaries were the same as those for radical inguinal LAD. All superficial inguinal nodes were removed en bloc. The cribriform fascia near the femoral canal was divided, and the deep inguinal lymph nodes were dissected. The fascia lata was completely preserved and sutured to the subcutaneous tissue. Sartorius muscle transposition was eliminated. Survival and morbidity data were retrospectively analyzed, and survival probabilities were calculated., Results: The median operative time for unilateral inguinal LAD was 45 minutes (range, 40-60 minutes). Median follow-up was 36 months (range, 10-130 months). A mean number of 12.5 nodes were removed per groin. One patient (1%) had a recurrence outside the borders of the fascia lata after 7 months of follow-up. The 3-year disease-free survival rate was 92.1% (100% for pN0, 91.3% for pN1, 80% for pN2, and 33.3% for pN3 disease). A total of 59 complications (29.3%) occurred, including wound infection (2.5%), skin necrosis (5.5%), lymphedema (11.8%), seroma formation (1.5%), lymphocele (5%), paresthesia (3.5%), and deep venous thrombosis (0.5%)., Conclusion: Inguinal dissections with preservation of the fascia lata for penile carcinoma patients without extranodal extension is as effective as the classic dissection technique but decreases complications related to groin dissection., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Heterogeneity of CD20 expression exists in chronic lymphocytic leukemia (CLL), therefore, we explored the prognostic significance of CD20 expression in Chinese patients with CLL. Multiparameter flow cytometry was used to detect the expression of CD20 in CD5(+) CD19(+) cells. In 172 CLL patients, the median expression percent of CD20 was 97.82% (range, 0-100), and the median mean fluorescence intensity (MFI) of CD20 in CLL cells was 731.45 (range, 0.00-9071.90). The percentage of CD20(+) cells in the patient group with mutated variable region of immunoglobulin genes (IGHV) was higher than in the non-mutant IGHV group (mean, 92.1% vs 80.4%, P < 0.001). There were no differences in the MFI of CD20(+) cells in all prognostic factor groups. Representation of the data using a receiver operating characteristic plot reflected separation between the two IGHV groups, with an area under the curve of 0.661 (95% confidence interval, 0.569-0.753). At the cut-off value of 60.3% for percentage of CD20, the sensitivity and specificity were 90.00% and 38.46%, respectively. Patients whose percentage of CD20 antigen was above 60.3% had longer treatment-free survival (hazard ratio, 0.452; 95% confidence interval, 0.232-0.884, P = 0.020). Percentage and MFI of CD20 were the variables not associated with treatment-free survival by multivariate Cox regression analysis (P < 0.05). High level of CD20 expression in de novo CLL appears to be associated with a good prognosis., (© 2013 Japanese Cancer Association.)

Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is one of the best-studied tumor suppressor genes which can promote cell proliferation and contribute to tumorigenesis. This study aimed to investigate the PTEN mRNA (Pm) expression level in patients with chronic lymphocytic leukemia (CLL) and healthy controls, and its correlation with prognostic factors. Quantitative polymerase chain reaction (qPCR) was used to detect Pm expression. Compared to controls, patients with CLL presented a lower expression level of Pm (p < 0.001). In univariate analysis, the expression level of Pm was significantly decreased in patients with Binet C (p < 0.001) and higher level of β2-microglobulin (β2-MG) (p = 0.036), lactate dehydrogenase (LDH) (p = 0.019) and ZAP-70 (p = 0.008). Higher Pm expression level was found in favorable cytogenetic aberrations (p = 0.016) and the group without p53 aberration (p = 0.005). Multivariate analysis showed that advanced Binet stage (p = 0.027) and p53 aberration (p = 0.007) were associated with a low PTEN expression level. Survival analysis showed that low expression of PTEN was associated with shorter time to first treatment (TTFT) (p = 0.040). These results indicate that PTEN might be a new prognostic marker in patients with CLL.

There is now strong evidence that B-cell receptor (BCR) signaling plays a major role in the development of chronic lymphocytic leukemia (CLL). The purpose of this study was to investigate the expression levels of some of the molecules involved in the signaling cascade originating from the BCR (Syk, Lyn, PLCγ2, ERK) and analyze possible correlations of mRNA levels with biological/clinical features. Our study population consisted of 92 consecutive patients with newly diagnosed CLL. Several genes of BCR signaling (Lyn, Syk, PLCγ2 and ERK) and ZAP-70 were measured by quantitative polymerase chain reaction (qPCR). The signaling molecules of BCR were strongly associated with each other, and ZAP-70 correlated well with Lyn, Syk, PLCγ2 and ERK. Associations between treatment response and Lyn, Syk, PLCγ2 and ERK were not found. Moreover, a higher level of Lyn mRNA was associated with a shorter treatment-free survival (TFS) (univariate analysis only; multivariate Cox analysis showed that only ZAP-70 and Binet stage were independent prognostic factors and associated with TFS). Though Lyn was not an independent prognostic factor, it still might be a new therapy target of CLL. BCR signaling provides perspectives for future development of an exciting new class of kinase inhibitors.

In order to determine the relationship between expression of cyclic nucleotide phosphodiesterase isoform 7B (PDE7B) and mantle cell lymphoma (MCL) progression, PDE7B mRNA expression was measured by qRT-PCR in 21 untreated MCL patients with bone marrow involvement and 20 healthy donors. The expression level of PDE7B was markedly higher in MCL patients compared with normal controls (P=0.001), and the higher level of PDE7B expression was associated with unfavorable cytogenetic characteristics in MCL. It was showed that higher expression of PDE7B might be a novel unfavorable prognostic indicator in MCL, which possess important clinical significance., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The purpose of the present study was to investigate the prognostic significance of murine double minute 4 (MDM4) in chronic lymphocytic leukemia (CLL) and to characterize the role of MDM4 in the p53 pathway. Full-length MDM4 (FL-MDM4), a splicing variant of MDM4 (S-MDM4) and murine double minute 2 (MDM2) mRNA expressions were detected by quantitative PCR in 140 Chinese patients with CLL, and primary CLL cells were treated in vitro with either fludarabine or Nutlin-3 to explore the interaction between p53 status and MDM4 or MDM2 expression. A marked increase of FL-MDM4 and S-MDM4 expressions were observed in the CLL patients with p53 aberrations (deletion and/or mutation) (P = 0.024, P < 0.001). A high level of S-MDM4 mRNA expression was associated with short treatment free survival (TFS) (P = 0.004). FL-MDM4 expression was significantly decreased after fludarabine treatment (P = 0.001) but increased after Nutlin-3 treatment (P = 0.008) of primary CLL cells without p53 aberrations. Both S-MDM4 and MDM2 expressions were significantly increased after fludarabine treatment of CLL cells without p53 aberrations (P = 0.013 and P = 0.030). MDM2 overexpression also occurred in CLL cells with p53 wild type after Nutlin-3 treatment (P = 0.018). FL-MDM4 and S-MDM4 overexpression are indicators of p53 aberrations in CLL patients, suggesting that those patients have a poor prognosis. FL-MDM4 inhibitory effects on p53 can be removed by MDM2-p53 and saved by Nutlin-3., (© 2012 Japanese Cancer Association.)

Human oncogene DEK has been shown to be upregulated in a number of neoplasms. The purpose of this study was to investigate DEK expression level in chronic lymphocytic leukemia (CLL), analyze the correlation between DEK expression and CLL prognostic markers, and characterize the role of DEK in the response to either chemotherapeutic drugs or nongenotoxic activators of the p53 pathway. DEK mRNA was evaluated by real-time quantitative reverse transcriptase-polymerase chain reaction (qPCR), and primary CLL samples were treated in vitro with either fludarabine or Nutlin-3 to explore the interaction of p53 status and DEK mRNA expression. The median expression levels of DEK mRNA were 6.792 × 10 (-2) (1.438 × 10 (-2) -3.201 × 10 (-1) ) in 65 patients with CLL. A marked increase of DEK mRNA expression was observed in the CLL patients with unmutated immunoglobulin heavy chain variable (IGHV) gene (p = 0.025), CD38-positive (p = 0.047), del(17p13) (p = 0.006). Both fludarabine and Nutlin-3 significantly downregulated DEK in the primary CLL cells which were with normal function of p53, or without deletion or mutation of p53 (p = 0.042, p = 0.038; p = 0.021, p = 0.017; p = 0.037, p = 0.017). However, the downregulation of DEK was not observed in the primary CLL cells which were with dysfunction of p53, or with deletion or mutation of p53 (p = 0.834, p = 0.477; p = 0.111, p = 0.378; p = 0.263, p = 0.378). These data show that DEK might be applied for the assessment of prognosis in patients with CLL, and fludarabine and Nutlin-3 regulate DEK expression depended on p53 status.

MicroRNAs (miRNAs) are of great importance in pathogenesis, diagnosis and prognosis of acute leukemia (AL). We studied five AL-related miRNAs to confirm the significance of these miRNAs in AL. Samples tested included acute myeloid leukemia (AML), 107 cases; acute lymphoblastic leukemia (ALL), 40 cases. Five AL-related miRNAs: miR-128, let-7b, miR-223, miR-181a and miR-155 expression were detected by qRT-PCR. Analysis showed that miRNA-128 expression was significantly higher in ALL (P<0.001). However, the let-7b and miR-223 expressions in ALL were significantly lower than in AML (P<0.001). Compared with normal controls, miR-128 expression was significantly higher in ALL (P<0.001), but there was no significant difference in AML (P=0.900). The expressions of Let-7b and miR-223 in AL group were higher than in normal controls (P<0.001). MiR-181a was quantitatively detected in 107 AML patients, and we found that the expression of miR181a in M1 or M2 patients was significantly higher compared with it in M4 or M5 (P=0.013). According to karyotype, 84 cases of AML were classified into three groups named favorable, moderate and poor. It was found that the expression of miR-181a in favorable prognosis group was significantly lower than in poor prognosis group (P=0.015). In FLT3-ITD mutation positive patients, the miR-155 expression was significantly higher than in the negative group (P=0.002). These results support that miR-128, let-7b, miR-223 and miR181a have a diagnosis value in AL, while miR-181a and miR-155 are of great prognostic significance in AML.

Objective: To investigate the incidence of serum immunoglobulin (Ig) paraprotein in chronic lymphocytic leukemia (CLL), and to explore its clinical associated laboratory features and prognostic implication., Methods: Serum protein electrophoresis and immunofixation electrophoresis were performed by automatic electrophoresis apparatus to identify serum Ig paraprotein. Immunonephelometry was used to measure serum Ig levels., Results: Out of 101 CLL patients, serum Ig paraprotein detection was found in 20 (19.8%) cases, 13 (12.9%) patients with IgG paraprotein, 7 (6.9%) patients with IgM paraprotein and 1(1.0%) patient with IgA paraprotein. Among these 20 cases, 1 patient had both IgG and IgM paraprotein, 2 patients had both κ and λ light chains. The incidence of serum IgG paraprotein was high in the group of advanced Binet stage (P = 0.032) and high level of thymidine kinase 1 (TK1) (P = 0.013). The incidence of serum IgM paraprotein was high in the group of advanced Binet stage (P = 0.037), high level of TK1 (P = 0.017) and cytogenetic abnormalities of del(11q22.3) (P = 0.006). With a median follow-up of 30 months (range 1 - 101 months), 66 patients received therapy after initial diagnosis. Survival analysis showed that the patients with serum Ig paraprotein had significantly shorter treatment-free survival (TFS) times than the patients without serum Ig paraprotein (P = 0.024). And the patients with serum IgM paraprotein had significantly shorter treatment-free survival (TFS) times than the patients without serum Ig paraprotein (P = 0.013). However, serum Ig paraprotein or IgM paraprotein was not independent prognostic factor., Conclusion: Serum Ig paraprotein can be detected in a subset of patients with CLL, which could be of value as a prognostic factor in CLL.

No confirmed risk factors are known to predict Richter syndrome (RS), and the value of clinical prognosticators conventionally applied to chronic lymphocytic leukemia (CLL) is not firmly established in this setting. The objective of this study was to present evidence for RS in Chinese patients with CLL and risk factors for CLL transformation to Richter syndrome. With a median follow-up of 43 months from CLL diagnosis in 149 Chinese patients, 16 (10.7%) patients progressed to diffuse large B-cell lymphoma (DLBCL). According to correlation analysis, a high level of lactate dehydrogenase (LDH) and CD38 positivity were found to be independent predictors of transformation to RS. Survival analysis showed that presence of RS, advanced Binet stage, high level of LDH, high level of β(2)-microglobulin, high concentration of thymidine kinase (TK), ZAP-70 and CD38 expression, unmutated immunoglobulin heavy chain variable (IGHV) gene status and del(17p13) were adverse factors in determining overall survival (OS). Only del(17p13) was strongly associated with survival by multivariate Cox regression analysis. Median OS after transformation was 16 months (95% confidence interval, 5.6-26.4 months). The results support that RS is associated with a poor outcome, and a policy of close monitoring and careful biopsy is needed in patients carrying transformation risk factors.

The white-rot fungus Phanerochaete chrysosporium has been widely used for the treatment of waste streams containing heavy metals and toxic organic pollutants. The development of fungal-based treatment technologies requires detailed knowledge of the relationship between bulk water quality and the physiological responses of fungi. A noninvasive microtest technique was used to quantify real-time changes in proton, oxygen, and cadmium ion fluxes following the exposure of P. chrysosporium to environmental toxic (2,4-dichlorophenol and cadmium). Significant changes in H(+) and O(2) flux occurred after exposure to 10 mg/L 2,4-dichlorophenol and 0.1 mM cadmium. Cd(2+) flux decreased with time. Reactive oxygen species formation and antioxidant levels increased after cadmium treatment. Superoxide dismutase activity correlated well with malondialdehyde levels (r(2) = 0.964) at low cadmium concentrations. However, this correlation diminished and malondialdehyde levels significantly increased at the highest cadmium concentration tested. Real-time microscale signatures of H(+), O(2), and Cd(2+) fluxes coupled with oxidative stress analysis can improve our understanding of the physiological responses of P. chrysosporium to toxic pollutants and provide useful information for the development of fungal-based technologies to improve the treatment of wastes cocontaminated with heavy metals and organic pollutants.

MicroRNAs (miRNAs) have been shown to play critical roles in regulating the progress of leukemia. We performed miRNA expression profile in six Chinese patients with chronic lymphocytic leukemia (CLL), and in peripheral B cells from pooled 30 healthy donors, using a platform containing 866 human miRNAs. The most frequent changes in miRNAs in CLL cells included downregulation of miR-126, miR-572, miR-494, miR-923, miR-638, miR-130a, miR-181a and miR-181b and up-regulation of miR-29a, miR-660, miR-20a, miR-106b, miR-142-5p, miR-101, miR-30b, miR-34a, miR-let-7f, miR-21 and miR-155. Among the miRNAs down-regulated in CLL cells, we showed that miR-181a/b expression levels were significantly lower in poor prognostic subgroups defined by unmutated immunoglobulin heavy chain variable status and p53 aberrations. Furthermore, under-expression of miR-181a and miR-181b was associated with shorter overall survival and treatment-free survival in CLL patients. We further evaluated fludarabine-induced apoptosis after transfection of primary CLL cells from 40 patients with miR-15a, miR-16-1, miR-34a, miR-181a and miR-181b mimics. Transfection of miR-34a, miR-181a and miR-181b mimics into CLL cells from p53 wild-type patients led to significant increase in apoptosis compared with miRNA control. However, enforced expression of these miRNAs had no effect on B-CLL cells from p53-attenuated patients. We further demonstrated that miR-181a and miR-181b inhibiting BCL-2, MCL-1 and X-linked inhibitor of apoptosis protein by direct binding to 3'UTR. Thus, these results suggest that miR-181a/b may play important roles in the pathogenesis of CLL and may provide a possible therapeutic avenue and a sensitive indicator of the activity of the p53 axis in CLL.

Background: Chronic lymphocytic leukemia (CLL) is heterogeneous with respect to prognosis and clinical outcome. Mutational status of immunoglobulin heavy chain variable region (IGHV) appears to be a particularly strong prognostic marker, but it is difficult to perform in a routine clinical laboratory. ζ-chain-associated protein kinase 70 kDa (ZAP-70) protein detected by flow cytometry is a strong surrogate marker of IGHV mutational status; however, it suffers from the lack of standardization., Methods: We investigated whether ZAP-70 mRNA expression level can be a prognostic factor in CLL. Real-time quantitative polymerase chain reaction was used to analyze ZAP-70 mRNA expression from 102 CLL patients., Results: The expression of ZAP-70 mRNA was significantly associated with Binet stage (P < 0.001), lactate dehydrogenase (P = 0.003), ZAP-70 protein (P = 0.018), IGHV mutational status (P = 0.038), and cytogenetic abnormality of del(17p13) or del(11q22.3) (P = 0.037) in CLL patients. According to receiver operating characteristic curve analysis for ZAP-70 mRNA and ZAP-70 protein, positive ZAP-70 mRNA (P = 0.006) was an adverse factor in determining the treatment free survival (TFS). In a multivariate Cox analysis of TFS, ZAP-70 mRNA is not ideal as an independent prognostic factor. However, ZAP-70 mRNA was statistically significant in predicting treatment response., Conclusion: This study demonstrated the value of determination of ZAP-70 mRNA in providing useful prognostic information in CLL patients. However, ZAP-70 mRNA is not an independent prognostic factor.