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The acute promyelocytic leukemia (APL) driver ZBTB16/RARα is generated by the t(11;17) (q23;q21) chromosomal translocation, which is resistant to combined treatment of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) or conventional chemotherapy, resulting in extremely low survival rates. In the current study, we investigated the effects of hyperthermia on the oncogenic fusion ZBTB16/RARα protein to explore a potential therapeutic approach for this variant APL. We showed that Z/R fusion protein expressed in HeLa cells was resistant to ATO, ATRA, and conventional chemotherapeutic agents. However, mild hyperthermia (42 °C) rapidly destabilized the ZBTB16/RARα fusion protein expressed in HeLa, 293T, and OCI-AML3 cells, followed by robust ubiquitination and proteasomal degradation. In contrast, hyperthermia did not affect the normal (i.e., unfused) ZBTB16 and RARα proteins, suggesting a specific thermal sensitivity of the ZBTB16/RARα fusion protein. Importantly, we found that the destabilization of ZBTB16/RARα was the initial step for oncogenic fusion protein degradation by hyperthermia, which could be blocked by deletion of nuclear receptor corepressor (NCoR) binding sites or knockdown of NCoRs. Furthermore, SIAH2 was identified as the E3 ligase participating in hyperthermia-induced ubiquitination of ZBTB16/RARα. In short, these results demonstrate that hyperthermia could effectively destabilize and subsequently degrade the ZBTB16/RARα fusion protein in an NCoR-dependent manner, suggesting a thermal-based therapeutic strategy that may improve the outcome in refractory ZBTB16/RARα-driven APL patients in the clinic.

To analyze the clinical manifestations, pathological characteristics, therapeutic effect and prognosis of diffuse large B-cell lymphoma (DLBCL) transformed from follicular lymphoma (FL).A total of 45 inpatients were eligible for criteria of histologic transformation from FL to DLBCL from January 2010 to January 2021, and their clinical characteristics, diagnosis, treatment and efficacy were collected and analyzed retrospectively.Among the 45 patients, transformation occurred at diagnosis in 27 cases, during " watch and wait " phase in 7 cases and after treatment of FL in 11 cases. The median age was 56 years old (ranged from 27 to 76 years), with 23 male and 22 female. The transformations were observed in 8 cases with low-grade and 37 cases with high-grade FL. Extranodal involvement was present in 26 cases, including bone marrow infiltration in 16 cases. There were 17 cases with anemia and 32 cases met the GELF criteria of high tumor burden. B symptoms were present in 12 cases. There were 38 cases with Ki-67≥50%. The germinal center B-cell-like (GCB) subtype of DLBCL was observed in 43 cases. Efficacy was evaluated in 45 cases. The OR, CR and PR rate were 80.0%, 60.0% and 20.0%, respectively. The OR,CR rate of patients received R-CHOP was higher than those of patients received other regimens (86.11% vs 55.55%,The OR and CR rates are higher in early transformation group of patients with DLBCL transformed from FL. Patients with anemia, B symptoms, POD24, and high-risk score have poor prognosis. IPI score is the independent prognosis factor for OS.滤泡性淋巴瘤转化的弥漫大B细胞淋巴瘤患者临床特征分析.分析滤泡淋巴瘤（FL）转化的弥漫大B细胞淋巴瘤（DLBCL）患者的临床表现、病理、疗效及预后的特点.选择并回顾性分析2010年1月至2021年1月符合条件的45例FL转化为DLBCL的患者，总结其临床特点、诊断、治疗方法和疗效.45例患者中，诊断时即发生转化的27例，选择观察等待之后发生转化的7例，FL治疗后发生转化的11例；男23例，女22例；中位年龄56(27-76)岁。低级别转化8例，高级别转化37例，26例出现结外侵犯，骨髓累及16例，贫血17例，高肿瘤负荷（GELF标准）32例, 伴B症状12例，Ki-67≥50%患者38例。43例转化为GCB型DLBCL。45例患者可评价疗效，所有患者初始化疗疗效评估总有效率（ORR）为80.0%，完全缓解（CR）率为60.0%，部分缓解（PR）率20%；R-CHOP和其他方案组患者ORR分别是86.11%和55.55%（FL转化为DLBCL患者诊断时即转化组ORR及CR率高；患者贫血及B症状、POD24及高危组预后差；IPI评分是影响OS的独立预后因素.

The aim of this study was to investigate the combined effect of n-3 fatty acids (EPA and DHA, at an EPA:DHA ratio of 150:500) and phytosterol esters (PS) on non-alcoholic fatty liver disease (NAFLD) patients. We conducted a randomised, double-blind, placebo-controlled trial. Ninety-six NAFLD subjects were randomly assigned to the following groups: the PS group (receiving 3·3 g/d PS); the FO group (receiving 450 mg EPA + 1500 mg DHA/d); the PS + FO combination group (receiving 3·3 g/d PS and 450 mg EPA + 1500 mg DHA/d) and the PO group (a placebo group). The baseline clinical characteristics of the four groups were similar. The primary outcome was liver:spleen attenuation ratio (L:S ratio). The percentage increase in liver–spleen attenuation (≤1) in the PS + FO group was 36 % (P = 0·083), higher than those in the other three groups (PS group, 11 %, P = 0·519; FO group, 18 %, P = 0·071; PO group, 15 %, P = 0·436). Compared with baseline, transforming growth factor-β (TGF-β) was significantly decreased in the three study groups at the end of the trial (PS, P = 0·000; FO, P = 0·002; PS + FO, P = 0·001) and TNF-α was significantly decreased in the FO group (P = 0·036), PS + FO group (P = 0·005) and PO group (P = 0·032) at the end of the intervention. Notably, TGF-β was reduced significantly more in the PS + FO group than in the PO group (P = 0·032). The TAG and total cholesterol levels of the PS + FO group were reduced by 11·57 and 9·55 %, respectively. In conclusion, co-supplementation of PS and EPA + DHA could increase the effectiveness of treatment for hepatic steatosis.

The purpose of this study was to identify the incidence, sites and main pathogens, and risk factors for infectious complications occurring in patients with adult acute myeloid leukemia (AML) during the first course of venetoclax combined with decitabine or azacitidine.A retrospective cohort analysis was performed of 81 patients with AML older than 14 years who received the first cycle of venetoclax combined with a hypomethylating agent (HMA) between March 2018 and March 2021 at our institution. Infectious complications, if any, were documented.Among a total of 81 cases of AML, 59 (72.8%) patients occurred infections, including fever without an identifiable source (28.8%), clinically documented infections (40.7%), and microbiologically documented infections (30.5%). The most commonly isolated organism in culture was Candida albicans, followed by Klebsiella pneumonia, and Pseudomonas aeruginosa. The 4-week and 8-week mortality rates were 3.7% and 7.4%, respectively. In multivariate analysis, a high proportion of blasts in bone marrow, decreased hemoglobin level, and fever with or without a documented infection at baseline were significant independent risk factors for infectious complications.Compared with conventional chemotherapy, the incidence of infectious complications of venetoclax combined with decitabine or azacitidine significantly decreased. Pretreatment high leukemia burden and fever were independent risk factors for infections.

Objective Some lines of evidence show that D2/D3 receptor partial agonist pramipexole may be effective in the treatment of extrapyramidal symptoms (EPS) and psychiatric symptoms of schizophrenia. Therefore, we analyzed whether a low dose of pramipexole (0.375-0.75 mg/day) has efficacy on EPS and symptoms of schizophrenia while maintaining tolerability. Methods Ten subjects with EPS [including drug-induced parkinsonism (DIP) and akathisia] were recruited in a stage-1, open-label pilot study. All the subjects were treated with a low dose of pramipexole. The evaluations were performed at baseline, day 3, week 1, week 2, week 4, week 6, and week 8. The ratings of SAS, BARS, PANSS, CDSS, and CGI-S and adverse effects (AE) were recorded in every visit. Results SAS total scores decreased significantly during the study in patients with DIP (P

FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) is one of the most common somatic mutations in acute myeloid leukemia (AML). However, the molecular structure characteristics and widely accepted prognostic factors for FLT3-ITD are still not well described. This study aimed to retrospectively examine 81 patients with FLT3-ITD-positive AML diagnosed and treated at the First Affiliated Hospital of Zhejiang University from December 2013 to March 2018 using the next-generation sequencing 185-gene platform. High variant allele frequency (VAF) [> 0.48, P = 0.0089 for overall survival (OS), P = 0.13 for relapse-free survival (RFS)], multiple ITDs (> 1 ITDs, P = 0.011 for OS, P = 0.033 for RFS) and longer insertion length (> 69 bp, P = 0.14 for OS, P = 0.0078 for RFS) predicted poor survival. The study further proposed an easily applicable scoring model for OS using the Least Absolute Shrinkage and Selector Operation (LASSO) Cox regression model. Also, an independent cohort of 30 patients was used for external model validation. The mode was expressed as follows: 0.659 × FLT3-ITD VAF + 0.375 × FLT3-ITD number + 0.807 × Age + 0.688 × DNMT3A + 1.939 × U2AF1 (FLT3-ITD VAF > 0.48 scored 1; FLT3-ITD number scored 1 if carried 1 ITD, 2 if carried ≥ 2 ITDs; age > 44 years scored 1, the presence of DNMT3A or U2AF1 scored 1; 0 for other conditions). It categorized patients into low-risk (L-R, score < 1, n = 20) and high-risk (H-R, score ≥ 1, n = 61) groups based on the risk score with a significant difference in survival (3-year OS, P < 0.0001; 3-year RFS, P = 0.0005). A prognostic nomogram that integrated these five factors was developed with a concordance index calculation [OS: 0.68, 95% CI (0.64-0.72)].

BackgroundHyperprolactinemia is a common adverse reaction in patients with schizophrenia who take antipsychotic drugs; it often leads to treatment non-compliance in patients and has an adverse effect on their prognosis.AimsThis study aimed to explore the risk factors of elevated prolactin (PRL) caused by risperidone (RIS) and olanzapine (OLZ) and the relationship between PRL and fasting plasma glucose and lipids.MethodsPatients with schizophrenia were divided into two groups: 264 patients who were taking RIS and 175 patients who were taking OLZ. These two groups were further divided according to serum PRL levels: an elevated PRL group (>30 ng/mL) and a normal PRL group (PRL ≤30 ng/mL). The demographics, medication dosage, fasting plasma glucose, total cholesterol and triglycerides were compared in the two groups. Logistic regression analysis was performed to explore the risk factors of elevated PRL levels.ResultsCompared with the OLZ group, the RIS group had a greater number of patients with elevated PRL (155/264 vs 58/175). Either the RIS or the OLZ group, the proportion of elevated PRL was greater in female patients (RIS: χ2=6.76, p=0.009; OLZ: χ2=12.98, pU=−3.73, pU=−2.31, p=0.021). In patients taking RIS, the elevated PRL subgroup took the drug for a longer period (U=−2.76, p=0.006) and had lower triglyceride levels (U=2.76, p=0.006). In patients taking OLZ, the elevated PRL subgroup had lower fasting plasma glucose levels (U=2.29, p=0.022). Logistic regression analysis showed that gender, dose and fasting glucose levels were significantly associated with elevated PRL levels (RIS: p=0.001, OLZ: pConclusionCompared with OLZ, RIS had a greater effect on PRL in patients with schizophrenia, and in patients with schizophrenia taking RIS or OLZ, gender and dose were significantly correlated with the PRL value. Moreover, the plasma glucose level of the group with elevated PRL was lower than that of the group with normal PRL. The results also showed that high serum PRL may be associated with a favourable glucose metabolic profile in patients with schizophrenia taking RIS or OLZ. Further studies are warranted to confirm this association.Trial registration numberNCT02640911

To investigate the related factors influencing plasma transfusion efficacy so as to improve the plasma transfusion efficiency.According to the clinical symptoms and the laboratorial results, the patients were divided into transfusion efficient and inefficient groups. A total of13090.8 units of plasma were transfused to 4423 patients. The clinical symptoms and the hemorrhage related index per- and pro-transfusion, plasma components sorts, storage time, and the dose of plasma (kg/ml) transfusion were analyzed.The largest transfusion volume of plasma were in intensive care unit (ICU) accounted for 30.36%, the largest blood plasma per patient transfusion was in cardiac surgery (3.96 U). The analysis of transfusion efficiency showed that in terms of patient age, there were difference in transfusion efficiency among the patients with different ages (P＜0.001). The effective transfusion rate in the group of age ＜18 was 53%, which was higher than that in group of age 18-60(41%) and group of age ＞60 (30%); in terms of sex, the effective transfusion rate in female group was higher than that in male group (42% vs 37%) (P＜0.001); in terms of transfusion plasma volume/body weight, there were differences in transfusion efficiency (P＞0.05). The multi-factor logistic regression analysis showed that there was no significant correlation among the plasma sorts, storage time of the plasma pre-transfusion and transfusion efficiency(P＞0.05). The analysis of the non-hemolytic fever reaction caused by plasma transfusion revealed that there was no statistical difference between the plasma and the leukocyte-depleted plasma groups (P＞0.05).The plasma transfusion effectiveness relates with age and sex, but not relates with the transfusion plasma voume/body weight, plasma sorts, and the duration of storage.4 423例次血浆输注效果的影响因素分析研究.探讨影响血浆输注效果的相关因素，以期进一步提高患者血浆输注有效率和临床输注的合理性.根据输血后患者临床症状改善情况和实验室凝血检测值将患者分为血浆输注有效和无效2组。对4 423例患者的基本临床资料和13 090.8 U的血浆输注过程中涉及的主要因素如输血浆前PT、APTT、血浆种类、保存时间、输注血浆体重比（kg/ml）等进行分类统计分析.外科监护室患者血浆用量最多，占总血浆输注比例最大（30.36%），人均用血浆量最大的科室为心外科（3.96 U）。从输注效果上看，不同年龄组患者的输血效果有差别（P＜0.001），＜18岁组患者血浆输注有效率（53%）高于18-60岁和＜60岁组，18-60岁组和＞60岁组患者血浆输注有效率分别为41%和30%；女性患者输血浆有效率（42%）高于男性（37%）（P＜0.001）；按不同血浆体重比进行血浆输注效果比较显示无显著差异（P＞0.05）；通过多因素Logistic回归分析，普通冰冻血浆、去白细胞血浆和新鲜冰冻血浆3类血浆的临床输注效果间没有差异；输注前血浆保存时间与输注效果之间无显著相关性。去白细胞血浆与未经去白的血浆相比，并未降低非溶血性发热性输血反应的发生率.血浆输注效果的主要影响因素有患者年龄、性别，但与血浆体重比、血浆种类和血浆保存时间关系不大；只要于保存期内输注，保存时间的长短与输注效果间没有显著相关性.

The aim of this study was to investigate the combined effect of n-3 fatty acids (EPA and DHA, at an EPA:DHA ratio of 150:500) and phytosterol esters (PS) on non-alcoholic fatty liver disease (NAFLD) patients. We conducted a randomised, double-blind, placebo-controlled trial. Ninety-six NAFLD subjects were randomly assigned to the following groups: the PS group (receiving 3·3 g/d PS); the FO group (receiving 450 mg EPA + 1500 mg DHA/d); the PS + FO combination group (receiving 3·3 g/d PS and 450 mg EPA + 1500 mg DHA/d) and the PO group (a placebo group). The baseline clinical characteristics of the four groups were similar. The primary outcome was liver:spleen attenuation ratio (L:S ratio). The percentage increase in liver-spleen attenuation (≤1) in the PS + FO group was 36 % (P = 0·083), higher than those in the other three groups (PS group, 11 %, P = 0·519; FO group, 18 %, P = 0·071; PO group, 15 %, P = 0·436). Compared with baseline, transforming growth factor-β (TGF-β) was significantly decreased in the three study groups at the end of the trial (PS, P = 0·000; FO, P = 0·002; PS + FO, P = 0·001) and TNF-α was significantly decreased in the FO group (P = 0·036), PS + FO group (P = 0·005) and PO group (P = 0·032) at the end of the intervention. Notably, TGF-β was reduced significantly more in the PS + FO group than in the PO group (P = 0·032). The TAG and total cholesterol levels of the PS + FO group were reduced by 11·57 and 9·55 %, respectively. In conclusion, co-supplementation of PS and EPA + DHA could increase the effectiveness of treatment for hepatic steatosis.

A novel polysaccharide FVPB2 was purified from fruiting bodies of Flammulina velutipes. Its structure was elucidated by monosaccharide composition and methylation analyses, UV-Visible and FTIR spectroscopy as well as NMR. FVPB2 was a homogeneous heteropolysaccharide (molecular weight ~ 1.50 × 104 Da) containing D-galactose, D-mannose, L-fucose, and D-glucose at molar ratio of 1.9:1.2:1:2.5. In vitro immunomodulatory studies showed FVPB2 induced proliferation of mouse spleen lymphocytes in a dose-dependent manner. The levels of IgM and IgG, secreted by B cells, increased after FVPB2 treatment. So FVPB2 has potential to be a new important immunomodulatory nutraceutical.

Background Cytoplasmic incompatibility (CI) is the most common phenotype induced by endosymbiont Wolbachia and results in embryonic lethality when Wolbachia-modified sperm fertilize eggs without Wolbachia. However, eggs carrying the same strain of Wolbachia can rescue this embryonic death, thus producing viable Wolbachia-infected offspring. Hence Wolbachia can be transmitted mainly by hosts’ eggs. One of the models explaining CI is “titration-restitution”, which hypothesized that Wolbachia titrated-out some factors from the sperm and the Wolbachia in the egg would restitute the factors after fertilization. However, how infected eggs rescue CI and how hosts’ eggs ensure the proliferation and transmission of Wolbachia are not well understood. Results By RNA-seq analyses, we first compared the transcription profiles of Drosophila melanogaster adult ovaries with and without the wMel Wolbachia and identified 149 differentially expressed genes (DEGs), of which 116 genes were upregulated and 33 were downregulated by Wolbachia infection. To confirm the results obtained from RNA-seq and to screen genes potentially associated with reproduction, 15 DEGs were selected for quantitative RT-PCR (qRT-PCR). Thirteen genes showed the same changing trend as RNA-seq analyses. To test whether these genes are associated with CI, we also detected their expression levels in testes. Nine of them exhibited different changing trends in testes from those in ovaries. To investigate how these DEGs were regulated, sRNA sequencing was performed and identified seven microRNAs (miRNAs) that were all upregulated in fly ovaries by Wolbachia infection. Matching of miRNA and mRNA data showed that these seven miRNAs regulated 15 DEGs. Wolbachia-responsive genes in fly ovaries were involved in biological processes including metabolism, transportation, oxidation-reduction, immunity, and development. Conclusions Comparisons of mRNA and miRNA data from fly ovaries revealed 149 mRNAs and seven miRNAs that exhibit significant changes in expression due to Wolbachia infection. Notably, most of the DEGs showed variation in opposite directions in ovaries versus testes in the presence of Wolbachia, which generally supports the “titration-restitution” model for CI. Furthermore, genes related to metabolism were upregulated, which may benefit maximum proliferation and transmission of Wolbachia. This provides new insights into the molecular mechanisms of Wolbachia-induced CI and Wolbachia dependence on host ovaries. Electronic supplementary material The online version of this article (10.1186/s12864-019-5977-6) contains supplementary material, which is available to authorized users.

Increasing precipitation has been predicted to occur in the karst areas in southwestern regions of China. However, it is little known how various plants respond to increasing precipitation in this region. Here we determined the impacts of water addition on leaf metabolites of grasses (Cymbopogon distans and Arundinella sitosa) and shrubs (Carissa spinarum and Bauhinia brachycarpa) in this area. Four levels of water additions (CK, T1, T2 and T3 indicating 0%, +20%, +40% and +60% relative to the current monthly precipitation, respectively) were designed. Sphingolipids substantially increased in the leaves of all four species with increasing water supply which suggests that these plants adopted biochemical strategy to tolerate the wet stress. However, both shrubs showed decreases in valine and threonine (amino acids), threonate, succinate and ascorbic acid (organic acids), galactose and rhamnose (sugars) and epicatchin and oleamides (secondary metabolites) with increasing water supply. Both grasses increased in the total metabolites at T1, but the total metabolites in A. sitosa significantly decreased at T2 and T3 while remains unchanged in C. distans. Tri-carboxylic acid cycle and amino acid metabolism in shrubs and shikimate pathway in grasses were strongly affected with water supply. Overall, shrubs and grasses respond differentially to variation in water addition in terms of metabolomics, which is helpful in understanding how plants respond to climate change.

Large-scale meta-analysis of genome-wide association data has identified six new risk loci (SIPA1L2, INPP5F, MIR4697, GCH1, VPS13C, and DDRGK1) for Parkinson's disease (PD). However, the characteristics of those loci in a Han Chinese population from mainland China are unknown. We examined genetic associations of VPS13C rs2414739, MIR4697 rs329648, GCH1 rs11158026, and SIPA1L2 rs10797576 with PD susceptibility in a Han Chinese population of 1028 sporadic PD patients and 1109 healthy controls. All subjects were genotyped for these loci using the Sequenom iPLEX Assay. We also conducted further stratified analysis according to age at onset and compared the clinical characteristics between minor allele carriers and non-carriers for each locus. However, we did not observe any significant difference in genotype distribution between PD patients and controls for the four loci, even after being stratified by age at onset. Besides, minor allele carriers cannot be distinguished from non-carriers based on their clinical features. Our findings first demonstrated that VPS13C rs2414739, MIR4697 rs329648, GCH1 rs11158026, and SIPA1L2 rs10797576 do not confer a significant risk for PD in Chinese population. Additional replication studies in other populations and functional studies are warranted to better validate the role of the four new loci in PD risk.

Dark count is one of the inherent noise types in single-photon diodes, which may restrict the performances of detectors based on these diodes. To formulate better designs for peripheral circuits of such diodes, an accurate statistical behavioral model of dark current must be established. Research has shown that there are four main mechanisms that contribute to the dark count in single-photon avalanche diodes. However, in the existing dark count models only three models have been considered, thus leading to inaccuracies in these models. To resolve these shortcomings, the dark current caused by carrier diffusion in the neutral region is deduced by multiplying the carrier detection probability with the carrier particle current at the boundary of the depletion layer. Thus, a comprehensive dark current model is constructed by adding the dark current caused by carrier diffusion to the dark current caused by the other three mechanisms. To the best of our knowledge, this is the first dark count simulation model into which incorporated simultaneously are the thermal generation, trap-assisted tunneling, band-to-band tunneling mechanisms, and carrier diffusion in neutral regions to evaluate dark count behavior. The comparison between the measured data and the simulation results from the models shows that the proposed model is more accurate than other existing models, and the maximum of accuracy increases up to 31.48% when excess bias voltage equals 3.5 V and temperature is 50 °C.

Chinese wolfberry or goji berry (Lycium barbarum) is an important traditional Chinese medicine. Its price and function has a close correlation with its geographical provenance. Illegal mislabeling motivated by commercial gains brings serious food safety problems and damages consumer confidence. In this work, a novel analytical strategy combined with chemometrics statistic tools was developed to determine the geographical origin of wolfberries from different provinces in China. Stable carbon isotopic ratios (δ13C) of wolfberry volatile compounds (i.e. limonene, tetramethylpyrazine, safranal, geranylacetone, and β-ionone) were determined by gas chromatography-combustion-isotope ratio mass spectrometry (GC-IRMS) with headspace-solid phase micro extraction (HS-SPME). Five types of SPME fiber (i.e. DVB/CAR/PDMS, CAR/PDMS, PDMS/DVB + OC, PDMS, and PA), extraction time, temperature and GC-IRMS conditions were comprehensively optimized to obtain the best adsorption of volatile compounds in wolfberry. Method integrity was assessed by comparing volatiles extracted using HS-SPME GC-IRMS with direct injection GC-IRMS and were in good agreement with each other. The geographical variations of volatile compounds using one-way analysis of variance (ANOVA) were explored for individual δ13C values in wolfberry samples from Gansu, Ningxia and Qinghai. Geographical origin of wolfberry was differentiated by linear discrimination analysis (LDA), with an accuracy of 89.16%, 87.77% and 85.87% for these three provinces, respectively. These results showed the combination of SPME and IRMS provides a rapid and valid method to determine the geographical origin of wolfberry.

The series of stereotypical physiological and behavioral changes that female insects exhibit after mating are called postmating responses (PMR). Wolbachia are widespread intracellular bacteria that are well known for their ability to manipulate the host’s reproductive behavior to facilitate their own maternal spreading. The effect of Wolbachia infection on insect hosts’ PMR is not well understood. Here, we showed that after mating with male Drosophila melanogaster infected with Wolbachia, the uninfected female showed a significant decrease in egg laying on the first day. Furthermore, both Wolbachia-infected and Wolbachia-uninfected females mated with infected males exhibited reduced feeding frequency, low receptivity to remating, and an extended median life span compared to those mated with uninfected males. To determine how Wolbachia triggered these alterations, we detected the influence of Wolbachia infection on the expression of some genes encoding seminal fluid proteins (Sfps) in D. melanogaster. These seminal fluid proteins are known to contribute to PMR upon transfer to females during copulation. We found that Acp26Aa, CG1656, and CG42474 were significantly downregulated in Wolbachia-infected males, whereas SP, CG1652, CG9997, and CG17575 showed no significant difference between Wolbachia-infected and Wolbachia-uninfected males. These results suggest that by decreasing the expression of some Sfps in the male hosts, Wolbachia may modulate sexual conflicts of their insect hosts in a way favoring females, thus benefit their own transmission through host populations. This study provides new insights into the host-endosymbiont interaction, which may support the application of endosymbionts for the control of pests and disease vectors. Wolbachia are among the most successful intracellular bacteria that can infect many insect species as well as filarial nematodes. Wolbachia infect host reproductive tissues and are best known for manipulating host reproductive systems to enhance their transmission through host populations. Mating may result in many physiological and behavioral changes in female insects, which are called postmating responses (PMR). Here, we found that after mating with Wolbachia-infected males, Drosophila melanogaster females showed altered PMR, including decreased feeding frequency, attenuated propensity to remating, and prolonged median survival, when compared to those mated with uninfected males. This could be due to a reduction of seminal fluid proteins induced by Wolbachia infection. These findings may raise new speculation about bacteria–host interactions and the ecological and evolutionary consequences of parasitic infection.

PD is a complex disease, and may result from gene–gene and gene–environment interactions. There are limited studies on gene–gene interactions in PD. We and others have previously shown that SNCA rs356219, LRRK2 (rs2046932 and rs7304279) and GAK (rs1564282) are risk factors in sporadic PD. Since the expression of SNCA and neurotoxicity of alpha-synuclein are affected by LRRK2 and GAK, we hypothesize that their genetic risk variants may interact with each other. Here we investigated the interaction of SNCA rs356219, LRRK2rs7304279 and rs2046932 and GAK rs1564282 using the Multifactor Dimensionality Reduction (MDR) in a Chinese PD patient–control series (534 patients and 435 controls) and the cumulative risk effect of SNCA, LRRK2 and GAK. The MDR analysis showed a significant gene–gene interaction between the rs356219 of SNCA, rs2046932 of LRRK2 and rs1564282 of GAK. Moreover, individuals with increasing numbers of variants had an increasing likelihood of having PD, compared with those carrying none of the variants. The estimated OR for developing PD in individuals carrying 3 variants was 5.89. We demonstrated for the first time that SNPs in SNCA, LRRK2 and GAK interacted with each other to confer an increased risk of PD. In addition, PD risk increased cumulatively with the increasing number of variants.

Different nitrogen (N) forms may cause changes in the metabolic profiles of plants. However, few studies have been conducted on the effects of amino acid-N on plant metabolic profiles. The main objective of this study was to identify primary metabolites associated with amino acid-N (Gly, Gln and Ala) through metabolic profile analysis using gas chromatography-mass spectrometry (GC-MS). Plants of pakchoi (Brassica campestris L. ssp. chinensis L.), Huawang and Wuyueman cultivars, were grown with different nitrogen forms (i.e., Gly, Gln, Ala, NO3−-N, and N starvation) applied under sterile hydroponic conditions. The fresh weight and plant N accumulation of Huawang were greater than those of Wuyueman, which indicates that the former exhibited better N-use efficiency than the latter. The physiological performances of the applied N forms were generally in the order of NO3−-N>Gln>Gly>Ala. The metabolic analysis of leaf polar extracts revealed 30 amino acid N-responsive metabolites in the two pakchoi cultivars, mainly consisting of sugars, amino acids, and organic acids. Changes in the carbon metabolism of pakchoi leaves under amino acid treatments occurred via the accumulation of fructose, glucose, xylose, and arabinose. Disruption of amino acid metabolism resulted in accumulation of endogenous Gly in Gly treatment, Pro in Ala treatment, and Asn in three amino acid (Gly, Gln and Ala) treatments. By contrast, the levels of endogenous Gln and Leu decreased. However, this reduction varied among cultivars and amino acid types. Amino acid-N supply also affected the citric acid cycle, namely, the second stage of respiration, where leaves in Gly, Gln and Ala treatments contained low levels of malic, citric and succinic acids compared with leaves in NO3−-N treatments. No significant difference in the metabolic responses was observed between the two cultivars which differed in their capability to use N. The response of primary metabolites in pakchoi leaves to amino acid-N supply may serve an important function in pakchoi adaptation to amino acid-N sources.

Background Genetic variability of methylenetetrahydrofolate reductase (MTHFR) may be associated with Parkinson's disease (PD). Its role in ethnic Chinese population is still unclear. Our study aimed to investigate whether MTHFR C677T variation was linked to PD risk in a Han Chinese population from mainland China. Methods To investigate the association with the risk of PD, we analyzed the single-nucleotide polymorphism C677T in MTHFR gene using a case–control methodology. A total of 1482 subjects included 765 patients with idiopathic PD, and 717 age- and sex-matched controls were recruited in this study. Results The T allele of MTHFR C677T was associated with a decreased risk of PD (OR = 0.80, 95% CI: 0.688–0.926, P = 0.003). Patients with CT + TT genotypes have a decreased risk of PD compared with those with CC genotypes (OR = 0.66, 95%CI: 0.532–0.813, P = 0.000). CT + TT subjects cannot be differentiated from CC subjects based on their clinical features. Conclusion We showed that the C677T polymorphism in MTHFR gene was associated with decreased PD susceptibility in a Han Chinese population from mainland China. Efforts to fully elucidate the pathophysiologic role of the variant in PD should be necessary.

Mitotic centromere-associated kinesin (MCAK) is a microtubule depolymerase indispensable for microtubule binding during spindle formation. The purpose of this study was to investigate the association of MCAK expression with squamous cell carcinoma of the oral tongue (SCCOT).Immunohistochemistry was used in 47 cases of SCCOT. Determination of proliferation and migratory capabilities was performed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Transwell chamber assay, respectively, on cells from the human tongue squamous cell carcinoma cell line Tca8113 that were transfected with MCAK small interfering RNA (siRNA).MCAK expression level in oral tongue cancer tissue is significantly higher (P.01) than that of corresponding normal tissue. In addition, high expression of MCAK is significantly associated with lymph node metastasis (P.05) and tumor staging (P.01). Moreover, gene silencing of MCAK suppresses proliferation and migration of Tca8113 cells (P.05; P.01).The expression of MCAK may be associated with the progression of SCCOT.

To evaluate the therapeutic efficacy of VICP+L-ASP/TKI on adult patients with B-ALL and to explore the influence factors.Forty-one adult B-ALL patients treated with VICP+L-ASP/TKI from August 2008 to June 2014 were following-up. The complete remission(CR) rate, toxicity, overall survival(OS) and event free survival(EFS) after induction treatment were analyzed, the therapeutic outcome of patients between different risk stratification subgroups was compared, the influence of standardized consolidatory and maintaining treatment as well as allogeneic hematopoietic stem cell transplantation(allo-HSCT) on survival time was analyzed.The early death not occurred in 41 patients with B-ALL including 37 cases with CR; the CR rate of 1 course treatment was 90.2%. The follow-up time lasted to March 17, 2015, the median follow-up time was 25(9-79) months; the 1 year OS rate was 75.3%, the EFS rate was 58.3%. Analysis of risk factors showed that the initial WBC count over 30×10Induction chemotherapy based on VICP+L-ASP/TKI and standardized consolidatory after remission according to the "2012 China adult acute lymphoblastic leukemia diagnosis and treatment expert consensus" can improve the therapeutic efficacy. The allo-HSCT should be actively performed for B-ALL paients with high risk(elevated initial WBC count and LDH level); at some time, the regularly monitoring MRD and adjusting therapeutic protocol according to monitoring result can promote the prognosis of adult B-ALL patients.

Alpha-synuclein gene (SNCA) polymorphisms have been associated with Parkinson's disease (PD). A recently published genome-wide association study (GWAS) meta-analysis from the USA and Europe found a strong association between SNCA rs356219 and PD. Considering the population-specific heterogeneity, we investigated the role of SNCA rs356219 as PD susceptibility in a large Han Chinese population of 685 patients and 569 controls. The SNCA rs356219-G allele was found to increase the risk to develop PD (OR = 1.81, 95% CI: 1.54-2.13, P = 5.71E-13). The meta-analysis revealed that the frequency of AG + GG genotypes higher in PD than in control subjects (OR = 1.85, 95% CI: 1.56-2.19, P = 0.00001) in the Asian population. PD patients with AG + GG genotypes were associated with earlier age at onset compared with those with AA genotype. No such significant association was observed in the clinical presentation for gender, age at onset, and onset symptoms. Our study provides strong support for the susceptibility role of SNCA rs356219 in sporadic PD in a Han Chinese population from mainland China and the meta-analysis also revealed a similar finding in the Asian population.

LASS2/TMSG1 was a novel tumor metastasis suppressor gene, which was first cloned by our laboratory from non-metastatic and metastatic cancer cell variants of human prostate carcinoma PC-3M using mRNA differential display in 1999. LASS2/TMSG1 could interact with the C subunit of vacuolar ATPase (V-ATPase, ATP6V0C) and regulate V-ATPase activity. In an attempt to provide molecular mechanism of the interaction between LASS2/TMSG1 and V-ATPase, we constructed four variant transfectants containing different functional domain of LASS2/TMSG1 and stably transfected the variants to human prostate cancer cell line PC-3M-1E8 cell with high metastatic potential. Results showed that there were no obvious differences of V-ATPase expression among different transfected cells and the control. However, V-ATPase activity and intracellular pH was significantly higher in the variant transfectants with Homeodomain of LASS2/TMSG1 than that in the control using the pH-dependent fluorescence probe BECEF/AM. Immunoprecipitation, immunofluorescence and immuno-electron microscope alone or in combination demonstrated the direct interaction of Homeodomain of LASS2/TMSG1 and ATP6V0C. Loss of Homeodomain markedly enhanced the proliferation ability but weakened the apoptotic effect of LASS2/TMSG1 in PC-3M-1E8 cells. These lines of results for the first time contribute to the conclusion that LASS2/TMSG1 could regulate V-ATPase activity and intracellular pH through the direct interaction of its Homeodomain and the C subunit of V-ATPase. Their interaction could play important roles in the apoptosis of tumor cells.

The tumor metastasis suppressor gene-1 (tmsg-1) was first cloned as a new tumor suppressor gene in our laboratory several years ago. Since then, however, despite the substantial progression that has been made in investigation of the biologic roles played by this gene, the manner in which it exerts its regulatory influence is still unknown. With transfection of various deletion or mutation constructs, we identified a potential enhancer and three potential silencers in the 5'-flanking region. However, it was particularly interesting to find that a region (+59 to +123 bp) of exon 1 exhibited a strong role in initiation of tmsg-1 gene transcription. Deletion of this region led to essentially complete loss of driving activity of exon-1 sequence on luciferase. Further analysis showed that transcription factors KLF6 and Sp1 are able to interact with each other and bind to their elements in this region. Co-transfection of pGL3-114/+123 with KLF6- and/or Sp1-expressing plasmids resulted in an elevation of luciferase activity and transcription level of tmsg-1, which was abolished by knockdown of KLF6 or Sp1. Analysis of metastatic capacity showed that cells with high metastatic capability exhibited a lower level of KLF6/TMSG-1 proteins with higher invasive capability and vice versa. Thus, we concluded that interaction of KLF6 and Sp1, together with their binding of elements in exon 1 are critical events in initiation of transcription of the tmsg-1 gene. These results reveal a hitherto unreported mechanism for initiation of transcription of the tmsg-1 gene.

Water-soluble pectin (WSP), chelated-soluble pectin (CSP) and acid-soluble pectin (ASP) were sequentially extracted from Canna edulis Ker residue, a by-product after the extraction of starch, and their physicochemical properties were studied. ASP was further separated through preparative column chromatography, leading to isolation of two fractions, ASPI and ASPII, which chemical features were analyzed by GC, GC–MS and NMR. Moreover, their behaviors in the simulated gastric and intestinal fluid were monitored. The results exhibit that C. edulis residue contains high amount of ASP derived from the heteropolysaccharide with rhamnogalacturonan as main chain. Furthermore, three pectins show gel formation and dissolution behaviors. It well suggests that C. edulis residue can be exploited for a good source of pectin for functional materials.

A drug-drug interaction occurs when the effect of one drug is altered by the presence of another drug which is generally associated with the induction of cytochrome P450s (CYPs) activity. Thus, unexpected treatment failures often happen resulting from inappropriate coadministration in fisheries. However, little information is available about CYP induction in fish. The reaction of difloxacin (DIF) biotransformation to sarafloxacin (SAR) belongs to N-demethylation catalyzed mainly by CYP(s). In order to supply useful information on CYP induction, the present study assessed the effects of fish-specific CYP inducers on DIF N-demethylation and enzyme kinetics in kidney cell of Chinese idle (CIK; grass carp (Ctenopharyngodon idellus)) by RP-HPLC. Results demonstrated that the amounts of SAR formation and enzymatic parameters Clint and Vmax were significantly increased due to beta-naphthoflavone (BNF) pretreatment. Therefore, we suggest that CYP1A may be involved in DIF N-demethylation in CIK. This study provides instructive information to ensure treatment success via avoiding CYP induction in fisheries.

As a complex wall system in flowering plants, the pollen outer wall mainly contains aliphatic sporopollenin; however, the mechanism for synthesizing these lipidic precursors during pollen development remains less well understood. Here, we report on the function of the rice tapetum-expressing TDR ( Tapetum Degeneration Retardation ) gene in aliphatic metabolism and its regulatory role during rice pollen development. The observations of transmission electron microscopy (TEM) and scanning electron microscopy (SEM) analyses suggested that pollen wall formation was significantly altered in the tdr mutant. The contents of aliphatic compositions of anther were greatly changed in the tdr mutant revealed by GC–MS (gas chromatography–mass spectrometry) testing, particularly less accumulated in fatty acids, primary alcohols, alkanes and alkenes, and an abnormal increase in secondary alcohols with carbon lengths from C29 to C35 in tdr . Microarray data revealed that a group of genes putatively involved in lipid transport and metabolism were significantly altered in the tdr mutant, indicating the critical role of TDR in the formation of the pollen wall. Also, a wide range of genes (236 in total—154 up-regulated and 82 down-regulated) exhibited statistically significant expressional differences between wild-type and tdr . In addition to its function in promoting tapetum PCD, TDR possibly plays crucial regulatory roles in several basic biological processes during rice pollen development.

Two one-dimensional complexes, [Ni(SCN)2(abba)2] n (abba = 4-(4-aminobenzyl)benzenamine) (1) and [Ni(SCN)2(aptba)2] n (aptba = 4-(4-aminophenylthio)benzenamine) (2), were synthesized and characterized by EA, IR, X-ray crystallography and thermal analysis. The single crystal X-ray structural analyses of 1 and 2 show the complexes to be 1D chain polymers as a result of dibenzenamine (dba) bridging. Each Ni is six-coordinate and adopts a slightly distorted octahedral geometry with four N atoms from four dba ligands and two N atoms from two NCS-groups. Adjacent Ni atoms and two dba ligands form a 24-membered macrocycle. Thermogravimetric analysis and differential thermogravimetric analysis of 2 show that the thermal decomposition of 2 includes four transitions.

Purpose A genome-wide association study (GWAS) has recently identified a novel single nucleotide polymorphism (SNP) rs356182 at SNCA that can modulate the risk of Parkinson's disease (PD) in Caucasian ancestry. The present study was designed to clarify the strength of the association in ethnic Chinese population. Methods Using a case–control methodology, we genotyped the SNP rs356182 to investigate the association with risk of PD. A total of 2205 ethnic Han Chinese study subjects comprising 1053 sporadic PD patients (581 males, 472 females) and 1152 controls (604 males, 548 females) were recruited from Mainland China. Additionally, the SHEsis software platform was applied for linkage disequilibrium (LD) analysis between rs356182 and another PD-associated synuclein SNP rs356219 we previously reported. Results The frequency of SNCA rs356182-G allele was significantly higher in PD group than that in controls (odds ratio (OR) = 1.470, 95% confidence interval (CI): 1.284–1.683, P = 2.306E − 8). Subjects carrying GG/AG genotype had an increased risk compared with the AA carriers (OR = 1.162, 95% CI: 1.143–2.274, P = 0.006). Among all the genotypes of rs356182, GG genotype showed the strongest association with risk of PD (GG vs. AG/AA, OR = 1.620, 95% CI: 1.368–1.919, P = 2.001E − 8). However, the gender, onset age, disease duration, Hoehn-Yahr stage, UPDRS scores and other clinical features were similar between GG genotype carriers and non-carriers. No LD between rs356182 and rs356219 was found in our population (r2 = 0.016 and D’ = 0.163). Conclusion Our study firstly demonstrates that SNCA rs356182 variant has an increased risk of susceptibility to PD in Han Chinese population. Further functional analysis is required to determine the role of this SNP in development of PD.

Sequence variants in SLC41A1 (solute carrier family 41 member 1) within the PARK16 locus have been reported to be associated with Parkinson's disease (PD). We performed direct DNA sequencing of the SLC41A1 gene in 100 early-onset PD cases. A novel intron variant (NM_173854.5:c.993-90delA) and a known synonymous-coding variant (NM_173854.5:c.339 C>T, causing p.Thr113Thr, rs11240569) were identified in the SLC41A1 gene. Then we genotyped the rs11240569 variant in a total of 2237 Han Chinese comprising of 1063 sporadic PD and 1174 controls to investigate the association with risk of PD, we also conducted further stratified analysis according to age at onset and compared the clinical characteristics of CC + CT subjects with TT subjects. In this study, we confirmed that the C allele of SLC41A1 (rs11240569) polymorphism reduces the risk to develop sporadic PD (P = 0.018). Additionally, subjects with CC + CT genotypes have a reduced risk compared to those with TT genotype (P = 0.022), the association was modestly seen among the younger age group (P = 0.05), but was not significant among the older age group (P = 0.641). Besides, we demonstrated that CC + CT subjects cannot be distinguished from TT subjects based on their clinical features. Our study, the first demonstrates that SLC41A1 (rs11240569) is associated with a lower risk of PD in a Han Chinese population from mainland China.

Reported herein is a renal anastomosing hemangioma which developed slowly in the past four years. A 25-year-old woman was found a mass localized in the upper portion four years ago, and only slow progression in the past four years. She underwent a laparoscopic partial nephrectomy of right kidney and diagnosed as anastomosing hemangioma. On histology the vascular components of the tumor had an anastomosing pattern without well-definite margins. Immunohistochemically, only endothelial markers (CD31, CD34) were expressed on the vascular components of tumor cells. Smooth muscle actin (SMA), cytokeratin (CK), EMA and S-100 and so on were all negative in the epithelioid tumor cells. The patient was alive at 16 months after operation, without any evidence recurrence or metastasis. Anastomosing hemangioma is an extremely rare vascular neoplasm; only 23 cases were previously described until now. Our report of anastomosing hemangioma arising from the kidney with slow progression will improve the knowledge of primary vascular tumors arising in the kidney.

Reported herein are simultaneous double primary clear cell carcinomas arising from liver and kidney. A 63-year-old man underwent a partial wedge nephrectomy of the right kidney in a surgical resection for hepatocellular carcinoma. Coincidently, on histology the tumors in liver and kidney were consisted of clear cancer cells, which arranged in haphazardly intermixed pattern without capsules. Immunohistochemically, the clear neoplastic cells in the liver were positive for HepPar-1, GPC3, and negative for nephrogenic markers; however, renal clear neoplastic cells were positive for CD10, RCC and Pax-8, but negative to liver-derived markers. These findings led to the diagnosis of simultaneous double primary clear cell carcinomas of kidney and liver. Multiple primary carcinomas of kidney and liver, especially both are primary clear cell carcinomas, are extremely rare neoplasms, only 1 case has been reported previously until now. To our knowledge, this is a report of multiple primary carcinomas arising from the liver and kidney and reminders us of differentiation diagnosis with carcinoma metastasis.

The current through a carbon nanotube field-effect transistor (CNFET) with cylindrical gate electrode is calculated using the nonequilibrium Greens function method in a tight-binding approximation. The obtained result is in good agreement with the experimental data. The theoretical approach is used to calculate the amplitude of the random-telegraph-signal (RTS) noise due to a single defect in the gate oxide of a long channel p-type CNFET. Considering a composite structure of gate insulators, which contains an inner insulator with a large dielectric constant (ϵ > 3.9) and an outer insulator with a dielectric constant of 3.9 (as for SiO2), the dependence of the RTS noise amplitude on the structure of composite gate insulators is investigated. It is found that the RTS amplitude increases apparently with the decreasing thickness of the inner gate insulator. If the inner insulator is too thin, even though its dielectric constant is as large as 80, the amplitude of the RTS noise caused by the charge of Q = +1e may amount to around 80% in the turn-on region.

Background The manganese superoxide dismutase (MnSOD) gene, which encodes a chief reactive oxygen species (ROS) scavenging enzyme, has been reported to be associated with the risk of developing sporadic Parkinson's disease (PD) in some Asian races and the synapsin III (SYN3) gene with some neuropsychiatric diseases. Objective: To explore the associations between the MnSOD and SYN III variations and PD in two Chinese populations from mainland China and Singapore. Methods We recruited 2342 subjects including 1200 sporadic PD patients and 1142 healthy controls from two independent Asian countries. Using a case-control methodology, we genotyped the single nucleotide polymorphisms (SNP) in MnSOD (rs4880) and SYN III (rs3788470, rs3827336, rs5998557) to explore the associations with risk of PD. Results The results showed the genotype distributions and minor allele frequencies (MAF) of MnSOD (rs4880) and SYN III (rs3788470, rs3827336, rs5998557) were not significantly different between PD patients and healthy controls in mainland China and Singapore, as well as in merged populations. Conclusions The variations of MnSOD (rs4880) and SYN III (rs3788470, rs3827336, rs5998557) were not major risk factors for PD among Chinese, at least in our study populations.

To study the clinicopathologic features and prognosis of plasmacytoid urothelial carcinoma (PUC) of the urinary bladder.The clinical and pathologic findings of 16 cases of PUC were retrospectively reviewed. Immunohistochemical study (MaxVision method) was carried out. The follow-up data were analyzed.There were altogether 15 males and 1 female. The age of patients ranged from 40 years to 85 years (median = 64 years). Most patients (15/16) presented with hematuria. The tumor cells were small to medium in size and contained eccentric nuclei and moderate to abundant eosinophilic cytoplasm, assuming a plasmacytoid appearance. The architectural pattern varied from loosely cohesive sheets to cords, papillae, small nests or gland-like structures. Most tumors invaded into the lamina propria or muscularis propria. Twelve of the 16 cases had concurrent conventional urothelial carcinoma component. Immunohistochemical study showed that the tumor cells in all cases were strongly positive for AE1/AE3, epithelial membrane antigen, CK7 and CK18. CK20 and uroplakin III were also expressed in 9 cases. CEA, p53, CD138, p63 and E-cadherin were positive in 12, 13, 15, 11 and 10 cases, respectively. Ki-67 index ranged from 5% to 70% (mean = 30%). All tumors were negative for vimentin, LCA, kappa/lambda light chains, S-100 protein, HMB 45,Melan A, smooth muscle actin and desmin. Follow-up information was available in 13 patients. The duration of follow up ranged from 3 months to 10 years. Three patients died of distant metastasis at 3, 27 and 60 months after the operation, respectively. One patient was alive with disease at 25 months. One was alive at 43 months with a prior recurrence. Another 8 patients were alive and disease free at 7 to 120 months.PUC of the urinary bladder is a rare variant of high-grade urothelial carcinoma. Immunohistochemical study with positivity for CK7, CK20, p63 and uroplakin III and negative staining for vimentin and LCA may be helpful in the differential diagnosis. PUC is a malignant tumor with high invasiveness, high recurrence rate and poor prognosis. Radical cystectomy is considered as the first line treatment for PUC.

To study the expression of carbonic anhydrase IX (CAIX), PAX2 and PAX8 in different types of renal epithelial tumor and their association with clinicopathologic characteristics.Immunohistochemical study by EnVision method was performed in order to assess the expression of CAIX, PAX2 and PAX8 in 155 cases of renal cell carcinoma and 4 cases of metastatic clear cell renal cell carcinoma (CCRCC). Ninety-six cases of non-neoplastic renal parenchymal tissue adjacent to CCRCC, 8 cases of clear cell hepatocellular carcinoma and 2 cases of clear cell hidradenoma were used as controls.CAIX was commonly expressed in CCRCC (94.0%, 63/67), of which 77.8% (49/63) showed strong positivity. CAIX was focally positive in papillary renal cell carcinoma, collecting duct carcinoma and urothelial carcinoma of renal pelvis. It was negative in chromophobe renal cell carcinoma, oncocytoma and adjacent non-neoplastic renal tissue. CAIX was also strongly expressed in the 4 cases of metastatic CCRCC. Focal expression of CAIX was demonstrated in the 8 cases of clear cell hepatocellular carcinoma and 2 cases of clear cell hidradenoma. The expression of CAIX in CCRCC did not correlate with tumor grading, clinical staging and presence of distal metastasis. On the other hand, PAX2 showed positive expression in different types of renal epithelial tumor, clear cell hepatocellular carcinoma and clear cell hidradenoma in various degrees. In contrast, PAX8 was commonly expressed in all types of renal epithelial tumor, with the exception of urothelial carcinoma of renal pelvis. PAX8 was not expressed in clear cell hepatocellular carcinoma and clear cell hidradenoma. Regarding diagnosis of CCRCC, CAIX demonstrated high sensitivity and specificity. PAX2 showed high specificity but low sensitivity. PAX8 was sensitive and specific in the diagnosis of renal epithelial tumor.CAIX is a useful immunohistochemical marker with high specificity and sensitivity in distinguishing CCRCC from other types of renal epithelial tumor and clear cell tumors of non-renal origin. PAX2 is a marker with high sensitivity and low specificity for diagnosis of renal epithelial tumors. PAX8 is typically expressed in renal epithelial tumors. The combined detection of CAIX, PAX2 and PAX8 is useful in the diagnosis and differential diagnosis of renal epithelial tumors.

To study the disease spectrum, clinical and pathologic features of primary cardiac neoplasms at a single medical institution during a period of eight years.The clinical and pathologic features of 81 cases of primary cardiac neoplasms encountered at the Affiliated Hospital of Medical College, Qingdao University from January, 2004 to December, 2011, either for cardiovascular surgery or as pathology consultation cases, were retrospectively reviewed. Immunohistochemical study was carried out in selected examples.Amongst the 81 cases studied, 73 cases (90.1%) were benign and 8 cases (9.9%) were malignant. Cardiac myxomas accounted for 97.3% (71/73) of all the benign cases. Six of the 8 malignant cases represented soft tissue sarcomas. The commonest presenting symptom was dyspnea. The histologic subtypes included myxoma (number = 71), angiosarcoma (number = 2), malignant fibrous histiocytoma (number = 2), hemangioma (number = 1), liposarcoma (number = 1), lymphoma (number = 1), myxofibrosarcoma (number = 1) and papillary fibroelastoma (number = 1).While the majority of primary cardiac neoplasms are myxomas, other tumor types do exist. Accurate histologic diagnosis and timely surgery are crucial in patient management.

BACKGROUND: The first large-scale meta-analysis of published genome-wide association studies (GWAS) in Parkinson's disease (PD) identified 5 new genetic loci (ACMSD, STK39, MCCC1/LAMP3, SYT11, and CCDC62/HIP1R). Very recently, a large-scale replication and heterogeneity study also reported that STK39 and CCDC62/HIP1R increased risk of PD in Asian and Caucasian populations. However, their roles still remain unclear in a Han Chinese population from mainland China. METHODS: We examined genetic associations of STK39 rs2102808 and CCDC62/HIP1R rs12817488 with PD susceptibility in a Han Chinese population of 783 PD patients and 725 controls. We also performed further stratified analyses by the age of onset and accomplished in-depth clinical characteristics analyses between the different genotypes for each locus. RESULTS: No significant differences were observed in the minor allele frequency (MAF) among cases and controls at the two loci (STK39 rs2102808: OR = 1.06, 95% CI = 0.91, 1.23, P = 0.467; CCDC62/HIP1R rs12817488: OR = 0.88, 95% CI = 0.76, 1.01, P = 0.072). Subgroup analyses by the age of onset also showed no significant differences among different subgroups of the two loci. In addition, minor allele carriers cannot be distinguished from non-carriers based on their clinical features at the two loci. CONCLUSIONS: We are unable to demonstrate the association between STK39 and CCDC62/HIP1R and PD susceptibility in a Han Chinese population from mainland China. Additional replication studies in other populations and functional studies are warranted to better validate the role of the two new loci in PD risk.

Objective Squamous cell carcinoma of the oral tongue (SCCOT) is one of the most common malignant carcinomas in the head and neck. Recurrence and/or metastasis often results in failure of treatment and decreases the survival of the patients. The purpose of this study is to investigate the effect of gene-silence of Kif2a on SCCOT in viro and in vivo. Study design Plasmid-mediated expression of Kif2a-siRNA (pGPU6/GFP/Kif2a) was employed to silence the expression of Kif2a in Tca8113 cells at both mRNA and protein levels. Tca8113 cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and growth of Tca8113 tumors was determined by intra-tumor injection of pGPU6/GFP/Kif2a in nude mice. Results Gene-silence of Kif2a suppressed Tca8113 cell proliferation. pGPU6/GFP/Kif2a synergized the tumor suppression effect of 5-Fluorouracil (5-Fu) on Tca8113 cells. Conclusions Our data support that Kif2a is a potential molecular target for the therapeutics of recurrent and metastatic SCCOT.