The nitrate transporter OsNPF7.9 mediates nitrate allocation and the divergent nitrate use efficiency between indica and japonica rice.

Nitrate allocation in Arabidopsis (Arabidopsis thaliana) represents an important mechanism for mediating plant environmental adaptation. However, whether this mechanism occurs or has any physiological/agronomic importance in the ammoniphilic plant rice (Oriza sativa L.) remains unknown. Here, we address this question through functional characterization of the Nitrate transporter 1/Peptide transporter Family (NPF) transporter gene OsNPF7.9. Ectopic expression of OsNPF7.9 in Xenopus oocytes revealed that the gene encodes a low-affinity nitrate transporter. Histochemical and in-situ hybridization assays showed that OsNPF7.9 expresses preferentially in xylem parenchyma cells of vasculature tissues. Transient expression assays indicated that OsNPF7.9 localizes to the plasma membrane. Nitrate allocation from roots to shoots was essentially decreased in osnpf7.9 mutants. Biomass, grain yield, and nitrogen use efficiency (NUE) decreased in the mutant dependent on nitrate availability. Further analysis demonstrated that nitrate allocation mediated by OsNPF7.9 is essential for balancing rice growth and stress tolerance. Moreover, our research identified an indica-japonica divergent single-nucleotide polymorphism occurring in the coding region of OsNPF7.9, which correlates with enhanced nitrate allocation to shoots of indica rice, revealing that divergent nitrate allocation might represent an important component contributing to the divergent NUE between indica and japonica subspecies and was likely selected as a favorable trait during rice breeding.

miR-126-5p Targets SP1 to Inhibit the Progression of Parkinson's Disease.

BACKGROUND: At present, symptomatic treatment may improve the life quality of Parkinson's disease (PD) patients to a certain extent but cannot completely cure PD. Therefore, it is urgent medical problem to be solved for improving the efficacy and safety of PD treatment. METHODS: SH-SY5Y and SK-N-SH cells were treated with 1-methyl-4-phenylpyridinium (MPP+) to establish PD model cells. miR-126-5p and specific protein-1 (SP1) expression levels were detected by quantitative Real-Time PCR (qRT-PCR). Western blot was applied to measure protein levels of SP1, Bax, and Bcl-2. The viabilities and apoptosis rates of treated cells were measured using cell counting kit-8 assay and flow cytometry analysis. Enzyme-linked immunosorbent assay was performed to measure TNF-α and IL-1ß releases. Interaction between miR-126-5p and SP1 was examined by dual-luciferase reporter assay. RESULTS: MPP+ treatment greatly downregulated miR-126-5p expression while upregulated SP1 expression in SH-SY5Y and SK-N-SH cells in a time- and does-dependent manner. Overexpression of miR-126-5p facilitated cell viability, while reduced cell apoptosis and inflammatory responses induced by MPP+ treatment. Moreover, SP1 was a target of miR-126-5p and could be negatively regulated by miR-126-5p. Overexpression of SP1 could reverse the effects of miR-126-5p on MPP+-administrated cells. CONCLUSION: Our results suggested that miR-126-5p attenuated the neurotoxicity induced by MPP+ in vitro through targeting SP1 (Graphical abstract), which further enhanced our understanding of the pathological mechanism of PD.

Combined Relativistic Ab Initio Multireference and Experimental Study of the Electronic Structure of Terbium Luminescent Compound.

A new terbium (III) luminescent compound {[Tb2(PDC)2(ox)(H2O)4](H2O)2}n was synthesized by the self-assembly of Tb3+ ions with 3,5-pyridinedicarboxylate (PDC) and oxalate (ox) ligands and characterized by fluorescence spectroscopy and single-crystal X-ray diffraction. The density functional theory (DFT) and high-level correlated ab initio wave function methods with Spin-Orbit Coupling correction (CASSCF/SO and CAS-NEVPT2/SOC) were successfully applied to predict the absorption and emission spectra of this strongly correlated lanthanide system in excellent agreement with the experimental results.

microRNA-374 inhibits proliferation and promotes apoptosis of mouse melanoma cells by inactivating the Wnt signalling pathway through its effect on tyrosinase.

Melanoma is one of the most malignant skin tumours with constantly increasing incidence worldwide. Previous studies have demonstrated that microRNA-374 (miR-374) is a novel biomarker for cancer therapy. Therefore, this study explores whether miR-374 targeting tyrosinase (TYR) affects melanoma and its underlying mechanism. We constructed subcutaneous melanoma models to carry out the following experiments. The cells were transfected with a series of miR-374 mimics, miR-374 inhibitors or siRNA against TYR. Dual luciferase reporter gene assay was used for the verification of the targeting relationship between miR-374 and TYR. Reverse transcription quantitative polymerase chain reaction and western blot analysis were conducted to determine the expression of miR-374, TYR, ß-catenin, B-cell leukaemia 2 (Bcl-2), Bcl-2 associated X protein (Bax), Low-density lipoprotein receptor-related protein 6 (LRP6), Leucine-rich repeat G protein-coupled receptor 5 (LGR5) and CyclinD1. Cell proliferation, migration, invasion, cell cycle distribution and apoptosis were evaluated using cell counting kit-8 assay, scratch test, transwell assay and flow cytometry respectively. TYR was proved as a putative target of miR-374 as the evidenced by the result. It was observed that up-regulated miR-374 or down-regulated TYR increased expression of Bax and decreased expressions of TYR, ß-catenin, LRP6, Bcl-2, CyclinD1 and LGR5, along with diminished cell proliferation, migration, invasion and enhanced apoptosis. Meanwhile, cells with miR-374 inhibitors showed an opposite trend. These findings indicated that up-regulated miR-374 could inhibit the expression of TYR to suppress cell proliferation, migration, invasion and promote cell apoptosis in melanoma cells by inhibiting the Wnt signalling pathway.

Nitrogen removal via a single-stage PN-Anammox process in a novel combined biofilm reactor.

This study developed a partial nitrification (PN) and anaerobic ammonia oxidation (Anammox) process for treating high-ammonia wastewater using an innovative biofilm system in which ammonia oxidizing bacteria grew on fluidized Kaldnes (K1) carriers and Anammox bacteria grew on fixed acryl resin carriers. The airlift loop biofilm reactor (ALBR) was stably operated for more than 4 months under the following conditions: 35 ± 2 °C, pH 7.5-8.0 and dissolved oxygen (DO) of 0.5-3.5 mg/L. The results showed that the total nitrogen removal efficiency reached a maximum of 75% and the total nitrogen removal loading rate was above 0.4 kg/(d·m3). DO was the most efficient control parameter in the mixed biofilm system, and values below 1.5 mg/L were observed in the riser zone for the PN reaction, while values below 0.8 mg/L were observed in the downer zone for the Anammox reaction. Scanning electron microscopy and Fluorescence In Situ Hybridization images showed that most of the nitrifying bacteria were distributed on the K1 carriers and most of the Anammox bacteria were distributed within the acryl resin carriers. Therefore, the results indicate that the proposed combined biofilm system is easy to operate and efficient for the treatment of high-ammonia wastewater.

Identification and functional characterization of two missense mutations in NDRG1 associated with Charcot-Marie-Tooth disease type 4D.

Charcot-Marie-Tooth disease type 4D (CMT4D) is an autosomal-recessive demyelinating form of CMT characterized by a severe distal motor and sensory neuropathy. NDRG1 is the causative gene for CMT4D. To date, only four mutations in NDRG1 -c.442C>T (p.Arg148*), c.739delC (p.His247Thrfs*74), c.538-1G>A, and duplication of exons 6-8-have been described in CMT4D patients. Here, using targeted next-generation sequencing examination, we identified for the first time two homozygous missense variants in NDRG1, c.437T>C (p.Leu146Pro) and c.701G>A (p.Arg234Gln), in two Chinese CMT families with consanguineous histories. Further functional studies were performed to characterize the biological effects of these variants. Cell culture transfection studies showed that mutant NDRG1 carrying p.Leu146Pro, p.Arg148*, or p.Arg234Gln variant degraded faster than wild-type NDRG1, resulting in lower protein levels. Live cell confocal microscopy and coimmunoprecipitation analysis indicated that these variants did not disrupt the interaction between NDRG1 and Rab4a protein. However, NDRG1-knockdown cells expressing mutant NDRG1 displayed enlarged Rab4a-positive compartments. Moreover, mutant NDRG1 could not enhance the uptake of DiI-LDL or increase the fraction of low-density lipoprotein receptor on the cell surface. Taken together, our study described two missense mutations in NDRG1 and emphasized the important role of NDRG1 in intracellular protein trafficking.

Gut microbiome-based medical methodologies for early-stage disease prevention.

Recent advancements highlight the important role of gut microbiome in human health. However, a variety of endogenous and exogenous factors, such as genes, foods, drugs, environmental pollutions, oxidative stress, etc., may interfere with the gut microbiome in vivo and increase risks of digestive system diseases, cardiovascular diseases, neurological diseases, obesity, diabetes, cancers, and so on. Abundant discoveries listed in this work support that changes in the composition of the gut microbiome may be potentially used as sensitive early-stage diagnostic biomarkers and that the gut microbiome could be a promising therapeutic target for systemic prevention of multiple human diseases. Interestingly, the microbial culturomics revolution makes it possible to identify much more species and several new species in the gut microbiome. Several innovative articles published by Science and Nature in 2016 further put forward the feasibility of these perspectives, lay grounds for establishing standardized human gut microbiome compositions, and are particularly important for monitoring dysbiosis of the gut microbiome and for precisely reshaping a dysfunctional gut microbiome. Hypothetically, keeping and reconstructing an optimized gut microbiome would be essential to prevent the occurrence of various human diseases. Hence, these advancements have impressive clinical implications for predicting abnormal healthy status of human beings and for preventing the initiation of systemic disorders at an early stage.

LncRNA UCA1 promotes renal cell carcinoma proliferation through epigenetically repressing p21 expression and negatively regulating miR-495.

Long non-coding RNAs have recently emerged as important regulators in the pathogenesis and progression of cancers. The long non-coding RNA urothelial carcinoma-associated 1 is reportedly upregulated and functions as an oncogene in some tumors. However, the role of urothelial carcinoma-associated 1 in renal cell carcinoma is not well elucidated so far. In this study, we found that urothelial carcinoma-associated 1 was overexpressed in renal cell carcinoma tissues compared with the adjacent normal tissues, and higher urothelial carcinoma-associated 1 expression levels were positively associated with advanced tumor stage and poor survival time in renal cell carcinoma patients. Further studies showed that knockdown of urothelial carcinoma-associated 1 suppressed renal cell carcinoma cell proliferation and S-phase cell number in vitro. Moreover, urothelial carcinoma-associated 1 was found to be associated with enhancer of zeste homolog 2, which suppressed p21 expression through histone methylation (H3K27me3) on p21 promoter. We also showed that knockdown of urothelial carcinoma-associated 1 increased the p21 protein expression through regulating enhancer of zeste homolog 2. In addition, bioinformatics analysis and dual-luciferase reporter assays confirmed that miR-495 was a target of urothelial carcinoma-associated 1 in renal cell carcinoma, and urothelial carcinoma-associated 1 promoted cell proliferation by negatively regulating miR-495. These findings illuminated that urothelial carcinoma-associated 1 promoted renal cell carcinoma progression through enhancer of zeste homolog 2 and interacted with miR-495. Overall, overexpression of urothelial carcinoma-associated 1 functions as an oncogene in renal cell carcinoma that may offer a novel therapeutic target for renal cell carcinoma patients.

Decreased expression of long noncoding RNA MEG3 affects cell proliferation and predicts a poor prognosis in patients with colorectal cancer.

Colorectal cancer (CRC) remains an important public health problem in the world. Long noncoding RNA (lncRNA) is an RNA molecular that is longer than 200 nucleotides and cannot be translated into a protein. Recent studies have shown that lncRNAs play important roles in carcinogenesis and cancer metastasis. The aim of this study was to evaluate the expression and biological role of lncRNA maternally expressed gene 3 (MEG3) in colorectal cancer. Quantitative real-time-PCR (qRT-PCR) was performed to investigate the expression of MEG3 in tumor tissues and corresponding nontumor colorectal tissues from 62 patients. The lower expression of MEG3 was remarkably correlated with low histological grade, deep tumor invasion, and advanced tumor node metastasis (TNM) stage. Multivariate analyses revealed that MEG3 expression served as an independent predictor for overall survival. Further experiments revealed that overexpressed MEG3 significantly inhibited CRC cell proliferation both in vitro and in vivo. In conclusion, our study demonstrated that MEG3 is involved in the development and progression of colorectal cancer by regulating cell proliferation and shows that MEG3 may be a potential diagnostic and prognostic target in patients with colorectal cancer.

Downregulation of BRAF activated non-coding RNA is associated with poor prognosis for non-small cell lung cancer and promotes metastasis by affecting epithelial-mesenchymal transition.

BACKGROUND: Recent evidence indicates that long noncoding RNAs (lncRNAs) play a critical role in the regulation of cellular processes, such as differentiation, proliferation and metastasis. These lncRNAs are found to be dysregulated in a variety of cancers. BRAF activated non-coding RNA (BANCR) is a 693-bp transcript on chromosome 9 with a potential functional role in melanoma cell migration. The clinical significance of BANCR, and its' molecular mechanisms controlling cancer cell migration and metastasis are unclear. METHODS: Expression of BANCR was analyzed in 113 non-small cell lung cancer (NSCLC) tissues and seven NSCLC cell lines using quantitative polymerase chain reaction (qPCR) assays. Gain and loss of function approaches were used to investigate the biological role of BANCR in NSCLC cells. The effects of BANCR on cell viability were evaluated by MTT and colony formation assays. Apoptosis was evaluated by Hoechst staining and flow cytometry. Nude mice were used to examine the effects of BANCR on tumor cell metastasis in vivo. Protein levels of BANCR targets were determined by western blotting and fluorescent immunohistochemistry. RESULTS: BANCR expression was significantly decreased in 113 NSCLC tumor tissues compared with normal tissues. Additionally, reduced BANCR expression was associated with larger tumor size, advanced pathological stage, metastasis distance, and shorter overall survival of NSCLC patients. Reduced BANCR expression was found to be an independent prognostic factor for NSCLC. Histone deacetylation was involved in the downregulation of BANCR in NSCLC cells. Ectopic expression of BANCR impaired cell viability and invasion, leading to the inhibition of metastasis in vitro and in vivo. However, knockdown of BANCR expression promoted cell migration and invasion in vitro. Overexpression of BANCR was found to play a key role in epithelial-mesenchymal transition (EMT) through the regulation of E-cadherin, N-cadherin and Vimentin expression. CONCLUSION: We determined that BANCR actively functions as a regulator of EMT during NSCLC metastasis, suggesting that BANCR could be a biomarker for poor prognosis of NSCLC.

Biocompatible KMnF3 nanoparticular contrast agent with proper plasma retention time for in vivo magnetic resonance imaging.

Nanoparticular MRI contrast agents are rapidly becoming suitable for use in clinical diagnosis. An ideal nanoparticular contrast agent should be endowed with high relaxivity, biocompatibility, proper plasma retention time, and tissue-specific or tumor-targeting imaging. Herein we introduce PEGylated KMnF3 nanoparticles as a new type of T1 contrast agent. Studies showed that the nanoparticular contrast agent revealed high bio-stability with bovine serum albumin in PBS buffer solution, and presented excellent biocompatibility (low cytotoxicity, undetectable hemolysis and hemagglutination). Meanwhile the new contrast agent possessed proper plasma retention time (circulation half-life t1/2 is approximately 2 h) in the body of the administrated mice. It can be delivered into brain vessels and maintained there for hours, and is mostly cleared from the body within 48 h, as demonstrated by time-resolved MRI and Mn-biodistribution analysis. Those distinguishing features make it suitable to obtain contrast-enhanced brain magnetic resonance angiography. Moreover, through the process of passive targeting delivery, the T1 contrast agent clearly illuminates a brain tumor (glioma) with high contrast image and defined shape. This study demonstrates that PEGylated KMnF3 nanoparticles represent a promising biocompatible vascular contrast agent for magnetic resonance angiography and can potentially be further developed into an active targeted tumor MRI contrast agent.

A variant within FGF1 is associated with Alzheimer's disease in the Han Chinese population.

Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by the accumulation of amyloid beta (Aß) plaques and Tau-containing neurofibrillary tangles in vulnerable brain areas. The progression of AD is well correlated with hippocampal neuron loss which highly suggests genes associated with neuron survival would be important for AD pathogenesis. According to the recent results of genome-wide association studies (GWAS) and other reported studies, we selected two single nucleotide polymorphisms (SNPs), rs3765728 within tumor protein p73 (P73), and rs34011 within fibroblast growth factor 1 (FGF1), both genes were related to neuron survival. We analyzed the distribution of rs3765728 and rs34011 in 1,083 Chinese subjects including 429 unrelated sporadic AD patients and 654 unrelated age and gender-matched control subjects. We found that the genotype distribution of rs34011 was significantly different between AD and control group (χ(2) = 9.048, df = 2, P = 0.011). Logistic regression manifested the risk of AD increased in TT genotype carriers in total subjects (Wald = 8.892, df = 1, P = 0.003, odds ratio [OR]:2.009, 95% confidence interval [95%CI]: 1.270-3.178). This effect was also found in APOE ϵ4 carrier group (Wald = 7.844, df = 1, P = 0.005, OR: 4.201, 95%CI: 1.539-11.472), suggesting the rs34011 has a synergetic effect of APOE on AD risk. However, no association was observed between rs3765728 and AD in the Han Chinese population (χ(2) = 0.431, df = 2, P = 0.806).

Synthesis, biological evaluation, 3D-QSAR studies of novel aryl-2H-pyrazole derivatives as telomerase inhibitors.

A series of novel aryl-2H-pyrazole derivatives bearing 1,4-benzodioxan or 1,3-benzodioxole moiety were designed as potential telomerase inhibitors to enhance the ability of aryl-2H-pyrazole derivatives to inhibit telomerase, a target of anticancer. The telomerase inhibition tests showed that compound 16A displayed the most potent inhibitory activity with IC(50) value of 0.9 µM for telomerase. The antiproliferative tests showed that compound 16A exhibited high activity against human gastric cancer cell SGC-7901 and human melanoma cell B16-F10 with IC(50) values of 18.07 and 5.34 µM, respectively. Docking simulation showed that compound 16A could bind well with the telomerase active site and act as telomerase inhibitor. 3D-QSAR model was also built to provide more pharmacophore understanding that could be used to design new agents with more potent telomerase inhibitory activity.

Synthesis, biological evaluation, and molecular docking studies of novel 1,3,4-oxadiazole derivatives possessing benzotriazole moiety as FAK inhibitors with anticancer activity.

1,3,4-Oxadiazole derivatives have drawn continuing interest over the years because of their varied biological activities. In order to search for novel anticancer agents, we designed and synthesized a series of new 1,3,4-oxadiazole derivatives containing benzotriazole moiety as potential focal adhesion kinase (FAK) inhibitors. All the synthesized compounds were firstly reported. Among the compounds, compound 4 shows the most potent inhibitory activity against MCF-7 and HT29 cell lines with IC50 values of 5.68 µg/ml and 10.21 µg/ml, respectively. Besides, all the compounds were assayed for FAK inhibitory activity using the TRAP-PCR-ELISA assay. The results showed compound 4 exhibited the most potent FAK inhibitory activity with IC50 values of 1.2±0.3 µM. Docking simulation by positioning compound 4 into the FAK structure active site was performed to explore the possible binding mode. Apoptosis which was analyzed by flow cytometry, demonstrated that compound 4 induced apoptosis against MCF-7 cells. Therefore, compound 4 may be a potential anticancer agent against MCF-7 cancer cell.

Herbal medicines for viral myocarditis.

BACKGROUND: Herbal medicines are used as treatment for viral diseases such as viral myocarditis, and numerous clinical trials have been conducted to investigate their efficacy. Despite this wealth of evidence, the role of herbal medicines in the treatment of viral myocarditis has yet to be established. This is an update of a review published in 2012. OBJECTIVES: To assess the benefits and harms of herbal medicines on clinical (e.g. mortality, incidence of complications) and indirect outcomes (e.g. cardiac function, biochemical response) in patients with viral myocarditis, irrespective of the patients' age, gender or type (including acute and chronic viral myocarditis). SEARCH METHODS: We searched CENTRAL (2013, Issue 1) on The Cochrane Library, MEDLINE (Ovid, 1946 to January Week 4 2013), EMBASE (Ovid, 1980 to 2013 Week 04) and LILACS (Bireme) on 1 February 2013. We previously searched The Chinese Biomedical Database (1979 to 2011), China National Knowledge Infrastructure (1979 to 2011), Chinese VIP Information (1989 to 2011), Chinese Academic Conference Papers Database and Chinese Dissertation Database (1980 to 2011), AMED (June 2011) and the Cochrane Complementary Medicine Field Trials Register (June 2011). We handsearched Chinese journals and conference proceedings. No language restrictions were applied. SELECTION CRITERIA: Randomised controlled trials of herbal medicines (with a minimum duration of seven days of treatment) compared with placebo, no intervention, or conventional interventions were included. Trials of herbal medicine plus a conventional drug versus the drug alone were also included. We included only trials that reported an adequate description of allocation sequence generation. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and evaluated trial quality. Information on adverse effects was collected from the trial reports. MAIN RESULTS: We did not identify any new trials with the updated search in February 2013. The 2011 update of this review included twenty randomised controlled trials involving 2177 people. All the trials were conducted and published in China. The controls included anti-arrhythmic drugs, corticosteroids, and antiviral therapies such as ribavirin or interferon. Combining the risk of bias for random sequence generation, allocation concealment, selective reporting, and incomplete outcome data, we assessed the included trials as being at a high risk of bias. Thirteen different herbal medicines were tested in the included trials. One of the trials reported outcomes on mortality. The trials reported electrocardiogram results, levels of myocardial enzymes, cardiac function, and adverse effects.Compared with supportive therapy, Astragalus membranaceus injection did not show a significant reduction in the number of patients that died of cardiac failure.A meta-analysis showed a significant effect ofAstragalus membranaceus injection plus supportive therapy on the number of participants with an abnormal electrocardiogram (RR 0.28, 95% CI 0.13 to 0.61), ST-T changes (RR 0.72, 95% CI 0.54 to 0.95), creatine phosphate kinase (CPK) levels (MD -21.54, 95% CI -33.80 to -9.28), and lactate dehydrogenase (LDH) levels (MD -30.33, 95% CI -46.78 to -13.88).Shengmai injection plus supportive therapy showed a significant effect on the number of patients with an abnormal electrocardiogram (RR 0.11, 95% CI 0.01 to 0.86), CPK levels (MD -103.90, 95% CI -114.97 to -92.83), LDH levels (MD -34.60, 95% CI -51.25 to -17.95), and on myocardial enzyme CK-MB levels (MD -10.87, 95% CI -14.50 to -7.24). Shengmai decoction plus supportive therapy showed a significant effect on improving quality of life measured by the SF-36 (MD 40.20, 95% CI 18.13 to 62.27) compared to supportive therapy. Data on adverse events were only available from six of the included trials and no serious adverse effects were reported. AUTHORS' CONCLUSIONS: Since no new trials were identified in the updated search in 2013, the conclusions remain the same as they were in 2012. There is no evidence of benefit of herbal medicine on all cause mortality. Some herbal medicines may lead to improvement of ventricular premature beat, electrocardiogram, levels of myocardial enzymes, and cardiac function in viral myocarditis. However, these findings should be interpreted with care, due to the risk of bias of the included studies, small sample size, and limited number of trials on individual herbs. Further robust trials are needed to explore the use of herbal medicines for viral myocarditis.

Folate grafted Prussian Blue entrapped with gadolinium(III) as a new contrast agent for tumor-targeted magnetic resonant imaging.

A new generation of magnetic resonant imaging (MRI) contrast agents will simultaneously possess characteristics of high relaxivity, biotargeting ability and nontoxicity, referring that they are helpful to acquire better contrast imaging in the region of interest (e.g., tumors) without health risks. Colloidal Prussian blue with quasi-zeolite structure was introduced as a new type of nanosized scaffold to entrap Gd(III) ions via ion exchange and folate, one kind of cancer-targeting ligand, was intentionally grafted on its surface. The nanoparticulate contrast agent has T1 relaxivity of up to 23.9 mM(-1) s(-1). In vivo MRI illustrated a clear contrast enhancement specifically on the ovarian tumors transplanted on mice at a low dose. Furthermore, the contrast agent is stable and free of cytotoxicity. Therefore it might be a promising new MRI contrast agent for clinical applications.

[Risk factors of prostate cancer in urban Qingdao: a case-control study].

OBJECTIVE: To investigate the risk factors of prostate cancer in urban Qingdao and provide some theoretical evidence for the scientific prevention and treatment of the disease. METHODS: We performed a hospital-based matched case-control study in Qingdao Municipal Hospital. The cases and controls were matched in age, gender, nationality and the place of residence. All the subjects were interviewed face to face in the hospital using a questionnaire, and the data analyzed by the conditional logistic regression method. RESULTS: According to the 258 valid questionnaires collected, the prostate cancer risk was significantly higher in the cases with a family history of cancer than in those without (OR = 2.58), and so was it in the men with the first spermatorrhea at the age of < or = 15 years than in those at the age of > or = 18 years (OR = 2.27). A decreased risk of prostate cancer was found among the men with the first experience of sexual intercourse between 25 to 30 years of age (OR = 0.76). An increased risk was shown in those with sexual intercourses > or = 4 times per week before 35 years old (OR = 2.57), masturbations > or = 3 times per week (OR = 2.30) and a drinking history (alcohol > or = 150 g/d) of > or = 10 years (OR = 2.83). CONCLUSION: Positive family history of cancer, earlier age of the first spermatorrhea, sexual intercourses > or = 4 times per week before 35 years old, frequent masturbations, and heavy drinking for more than 10 years are risk factors for prostate cancer.

[CT manifestations of liver involvement in children with Langerhans cell histiocytosis].

OBJECTIVE: To investigate the computed tomography (CT) manifestations of liver involvement in children with Langerhans cell histiocytosis (LCH). METHODS: Retrospective analysis was performed on 9 LCH children with liver involvement confirmed by clinical, laboratory and pathological examinations to investigate the CT manifestations of this condition. These children, including 6 males and 3 females, had undergone both plain CT scan and dual-phase (the arterial and portal venous phases) contrast-enhanced CT scan. RESULTS: The main CT manifestations included hepatomegaly (8 cases); periportal dendritic hypodense lesions or "periportal halo sign" (7 cases) which were mildly or moderately enhanced in the arterial phase; intrahepatic bile duct dilatation (5 cases); lymphadenopathy in the hepatic hilar or retroperitoneal region (4 cases); and diffuse small hypodense nodules (3 cases), which showed annular enhancement on the contrast-enhanced CT scan. CONCLUSIONS: CT findings may be helpful in the early diagnosis and treatment of LCH in children.

Two novel heterozygote mutations of ATM in a Chinese family with dystonia-dominant ataxia telangiectasia and literature review.

Background: Ataxia-telangiectasia (A-T) is an autosomal recessive disorder with high clinical heterogeneity. A-T may present in complicated variable forms, including classic A-T and milder form of AT. Contrary to the classic A-T, the milder form does not present the cardinal features of A-T such as ataxia and telangiectasia. A few ATM mutations have been reported in variant A-T cases manifesting isolated generalized or segmental dystonia without any signs of classical A-T. Methods: An A-T pedigree with predominant dystonia was collected. Genetic testing was performed by targeted panel of genes involved in movement disorders. The candidate variants were further confirmed by Sanger sequencing. We then reviewed previously published literatures of genetically confirmed A-T cases with predominant dystonia and summarized the clinical characteristics of dystonia-dominant A-T. Results: Two novel ATM mutations, p.I2683T and p.S2860P, were identified in the family. The proband presented isolated segmental dystonia without any signs of ataxia and telangiectasias. We reviewed the literatures and found that the patients with dystonia-dominant A-T tend to have a later-onset and slower progression of the disease. Conclusion: To our knowledge, this is the first report of A-T patient with predominant dystonia in China. Dystonia may appear as one of the predominant manifestations or initial symptom of A-T. Early ATM genetic testing should be considered for those patients with predominant dystonia, despite without accompanying ataxia or telangiectasia.

[Pro-oxidation status of rotator cuff tissue and expression of Beclin-1 and mTOR in patients with rotator cuff injury].

OBJECTIVE: To explore pro-oxidative state of rotator cuff tissue and expression levels of Beclin-1 and mam-malian target of rapamycin(mTOR) in patients with acute and chronic rotator cuff injury, and then analyzed relationship between rotator cuff injury and oxidative stress and autophagy. METHODS: Forty patients with rotator cuff injury were seleceted from July 2019 to December 2020, and divided into male chronic injury group, male acute injury group, female chronic injury group, and female acute injury group, 10 patients in each group. All patients were performed rotator cuff repair under arthroscopy. The sample of tendon at the rotator cuff injury site of the patient was taken during operation, and total reactive oxygen species (ROS) and superoxide dismutase(SOD) were detected by detection kit;expression of Beclin-1 and mTOR mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR), and Western-blot was applied to detect protein expression of Beclin-1 and p-mTOR/mTOR. RESULTS: There were no significant difference in expression of ROS, SOD, Beclin-1mRNA and mTOR mRNA between male and female chronic injury groups, and between male and female acute injury groups (P>0.05); ROS, SOD and Beclin-1mRNA in male chronic injury group were higher than those in male chronic injury group, while mTOR mRNAand protein decreased (P<0.05);ROS, SOD and Beclin-1 mRNA in female chronic injury group were up-regulated compared with female acute injury group, while mTOR mRNA was down-regulated (P<0.05). CONCLUSION: Chronic rotator cuff injury is more likely to stimulate the pro-oxidation state of rotator cuff tissue than acute rotator cuff injury, which could up-regulating expression of autophagy factor Beclin-1 and down-regulating expression of mTOR. Therefore, patients with chronic rotator cuff injury may have higher levels of oxidative stress and autophagy.