Optical coherence tomography in patients with Wilson's disease.

BACKGROUND: Morphological changes of retina in patients with Wilson's disease (WD) can be found by optical coherence tomography (OCT), and such changes had significant differences between neurological forms (NWD) and hepatic forms (HWD) of WD. The aim of this study was to evaluate the relationship between morphological parameters of retina and brain magnetic resonance imaging (MRI) lesions, course of disease, type of disease, and sexuality in WD. METHODS: A total of 46 WD patients and 40 health controls (HC) were recruited in this study. A total of 42 WD patients were divided into different groups according to clinical manifestations, course of disease, sexuality, and brain MRI lesions. We employed the Global Assessment Scale to assess neurological severity of WD patients. All WD patients and HC underwent retinal OCT to assess the thickness of inner limiting membrane (ILM) layer to retinal pigment epithelium layer and inner retina layer (ILM to inner plexiform layer, ILM-IPL). RESULTS: Compared to HWD, NWD had thinner superior parafovea zone (108.07 ± 6.89 vs. 114.40 ± 5.54 µm, p < .01), temporal parafovea zone (97.17 ± 6.65 vs. 103.60 ± 4.53 µm, p < .01), inferior parafovea zone (108.114 ± 7.65 vs. 114.93 ± 5.84 µm, p < .01), and nasal parafovea zone (105.53 ± 8.01 vs. 112.10 ± 5.44 µm, p < .01) in inner retina layer. Course of disease influenced the retina thickness. Male patients had thinner inner retina layer compared to female patients. CONCLUSION: Our results demonstrated that WD had thinner inner retina layer compared to HC, and NWD had thinner inner retina layer compared to HWD. We speculated the thickness of inner retina layer may be a potential useful biomarker for NWD.

Analysis of risk factors for neurological symptoms in patients with purely hepatic Wilson's disease at diagnosis.

OBJECTIVE: To analyze and explore the risk factors for neurological symptoms in patients with purely hepatic Wilson's disease (WD) at diagnosis. METHODS: This retrospective study was conducted at the First Affiliated Hospital of the Guangdong Pharmaceutical University on 68 patients with purely hepatic WD aged 20.6 ± 7.2 years. The physical examinations, laboratory tests, color Doppler ultrasound of the liver and spleen, and magnetic resonance imaging (MRI) of the brain were performed. RESULTS: The elevated alanine transaminase (ALT) and aspartate transaminase (AST) levels and 24-h urinary copper level were higher in the purely hepatic WD who developed neurological symptoms (NH-WD) group than those in the purely hepatic WD (H-WD) group. Adherence to low-copper diet, and daily oral doses of penicillamine (PCA) and zinc gluconate (ZG) were lower in the NH-WD group than those in the H-WD group. Logistic regression analysis showed that insufficient doses of PCA and ZG were associated with the development of neurological symptoms in patients with purely hepatic WD at diagnosis. CONCLUSION: The development of neurological symptoms in patients with purely hepatic WD was closely associated with insufficient doses of PCA and ZG, and the inferior efficacy of copper-chelating agents. During the course of anti-copper treatment, the patient's medical status and the efficacy of copper excretion should be closely monitored.

Elevated PTTG1 predicts poor prognosis in kidney renal clear cell carcinoma and correlates with immunity.

Background: PTTG1 has been reported to be linked with the prognosis and progression of various cancers, including kidney renal clear cell carcinoma (KIRC). In this article, we mainly investigated the associations between prognosis, immunity, and PTTG1 in KIRC patients. Method: We downloaded transcriptome data from the TCGA-KIRC database. PCR and immunohistochemistry were used, respectively, to validate the expression of PTTG1 in KIRC at the cell line and the protein levels. Survival analyses as well as univariate or multivariate Cox hazard regression analyses were used to prove whether PTTG1 alone could affect the prognosis of KIRC. The most important point was to study the relationship between PTTG1 and immunity. Results: The results of the paper revealed that the expression levels of PTTG1 were elevated in KIRC compared with para-cancerous normal tissues, validated by PCR and immunohistochemistry at the cell line and the protein levels (P < 0.05). High PTTG1 expression was related to shorter overall survival (OS) in patients with KIRC (P < 0.05). Through univariate or multivariate regression analysis, PTTG1 was confirmed to be an independent prognostic factor for OS of KIRC (P < 0.05), and its related seven pathways were obtained through gene set enrichment analysis (GSEA; P < 0.05). Moreover, tumor mutational burden (TMB) and immunity were found to be significantly connected with PTTG1 in KIRC (P < 0.05). Correlations between PTTG1 and immunotherapy responses implied that the low-PTTG1 group was more sensitive to immunotherapy (P < 0.05). Conclusions: PTTG1 was closely associated with TMB or immunity, and it had a superior ability to forecast the prognosis of KIRC patients.

Highly Expressed LINC00958 Modulates the Growth and Epithelial-Mesenchymal Transition of Bladder Cancer Cells Through SAPK/JNK Signaling Pathway.

Objective: To determine the expression of LINC00958 (BLACAT2) in bladder cancer (BC), the most common malignancy in the urinary system, and to determine its exact mechanism of action, so as to provide novel references for future clinical diagnosis and treatment of BC and lay a foundation for the follow-up research on LINC00958. Materials and Methods: Human bladder transitional cell carcinoma cells (T24 and J82) and human normal urothelial cells (SV-HUC-1) were purchased to detect the expression of LINC00958 and SAPK/JNK signaling pathway-related proteins. sh-LINC00958 targeting to silence LINC00958 expression and corresponding negative blank (sh-Control) were transfected into T24 and J82. Additionally, BC cells cultured with SP600125 (SP600125 group), a specific inhibitor of SAPK/JNK signaling pathway, and those cultured with the same amount of normal saline (Blank group) were also constructed. Cell growth capacity, cell invasiveness, and expression of epithelial-mesenchymal transition (EMT)-associated proteins were determined using CCK-8 & clone formation assays, Transwell assay, and Western blot, respectively. Results: The online databases Gene Expression Profiling Interactive Analysis, European Bioinformatics Institute, and StarBase revealed elevated LINC00958 expression in BC, and a potential association between LINC00958 and patient prognosis and survival. PCR results showed that LINC00958 was increased in T24 and J82 compared with the sh-Control group (p < 0.05). The results of biological behavior test revealed that the proliferation and invasiveness capacity of the sh-LINC00958 group decreased, while that of the SP600125 group increased compared with the Blank group (both p < 0.05). In the rescue experiment, the influence of sh-LINC00958 on BC cells was completely reversed by SP600125 (p > 0.05); In addition, the expression of E-cadherin, an EMT marker protein, was lower compared with the SH-LINC0958 group, while the Vimentin expression was higher (p < 0.05). Similarly, the wound-healing assay determined reduced cell healing rate in the sh-LINC00958 group (p < 0.05), and there was no difference between the sh-LINC00958+SP600125 group and the sh-Control group (p > 0.05). Conclusion: LINC00958 shows elevated expression in BC and promotes the growth and EMT of BC cell via inhibiting the SAPK/JNK signaling pathway, which has important potential as a new clinical diagnostic marker and therapeutic target for BC.

Linear structural features of Wilson's disease and its correlation with neurological symptoms.

To measure the linear structure of the brain in patients with Wilson's disease (WD) and analyze its correlation with neurological symptoms. A total of 174 patients diagnosed with WD were enrolled. According to the type of clinical presentation, the patients with WD were divided into two groups: neurological (NWD) and hepatic (HWD). Sixty healthy volunteers were assigned to a control group. All patients with WD and healthy controls underwent brain magnetic resonance imaging (MRI). The severity of the neurological symptoms was assessed using the Burke Fahn Marsden Movement subscale (BFM-M). Linear brain measurements were performed using T1-weighted MRI scans of all the patients, and the correlation between these linear indices and BFM-M score was investigated. The Huckman index, third ventricle width, and sulcus width of the NWD group were significantly higher than those of the HWD and control groups (P < .05). The frontal horn index, ventricular index, and lateral ventricular body width index of the NWD group were significantly lower than those of the HWD and control groups (P < .05). The Huckman index and third ventricle width of the HWD group were higher than those of the control group (P < .05), whereas the body width index of the lateral ventricle was lower than that of the control group (P < .05). The BFM-M score correlated with the Huckman index (r = 0.29, P < .05), third ventricle width (r = 0.426, P < .001), and lateral ventricular body width index (r = -0.19, P < .05). This study demonstrated significant changes in the linear structure of patients with WD. Linear brain measurement analysis could be used as a potential method to assess the severity of neurological symptoms in WD.

Co-overexpression of VEGF and Smad7 improved the therapeutic effects of adipose-derived stem cells on neurogenic erectile dysfunction in the rat model.

Cavernous nerve injury is the main cause of erectile dysfunction (ED) after radical prostatectomy (RP). In our previous study, injection of adipose-derived stem cells (ADSCs) into the cavernosum can repair damaged cavernosum nerves and ED can be restored to a certain extent. In order to improve these therapeutic effects, we evaluated the efficacy of ADSCs co-modified with VEGF and Smad7 in a rat model. SD rats were randomly divided into six groups: a sham surgery group, and the five bilateral cavernous nerve injury (BCNI) groups were injected with ADSC or ADSCs genetically modified by VEGF (ADSC-V), Smad7 (ADSC-S), or VEGF&Smad7 (ADSC-V&S) or phosphate-buffered saline (PBS). The results indicated that the erectile function of the ADSC-V, ADSC-S, and ADSC-V&S groups was significantly recovered, and the erectile function of the ADSC-V&S group was more distinctly recovered as compared to the other groups. The same results are shown in the expression of neuronal nitric oxide synthase and the smooth muscle/collagen ratio of penile tissue comparing the ADSC-V&S group to the ADSC-V and ADSC-S group. These experimental data suggest that ADSCs co-overexpressed with VEGF and Smad7 can significantly improve erectile function after BCNI. This study provides new therapeutic thoughts for ED following RP.

Comprehensive analysis of the relationship between the ferroptosis and tumor-infiltrating immune cells, mutation, and immunotherapy in breast cancer.

Background: Ferroptosis is a kind of programmed cell death that is characterized by iron dependence. It differs from apoptosis, necrosis, autophagy, pyroptosis, and other types of cell death. Some studies have found that most of the genes involved in the regulation of ferroptosis or act as markers of ferroptosis are related to the poor prognosis of cancer patients. Methods: This study evaluated the expression, mutation, and copy number variation (CNV) of 60 previously reported ferroptosis genes in breast cancer samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Unsupervised clustering of breast cancer samples with ferroptosis genes was performed, followed by enrichment analysis with Gene Set Variation Analysis (GSVA), mutation display, and correlation analysis of clinical characteristics. Based on the analysis of differences among groups, the ferroptosis-related genes were identified, and the consistent clustering of breast cancer samples was performed. The characteristic genes were screened by stochastic forest algorithm and COX analysis, and a ferroptosis score (ferr.score) model was constructed to evaluate the prognosis of breast cancer patients. Results: Copy number amplification and deletion of ferroptosis genes are common in breast cancer. Breast cancer patients grouped by ferroptosis gene clusters showed significant differences in survival, immune cell infiltration, and enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways. The ferroptosis-related differential genes were identified by comparison among clustering groups of ferroptosis gene. Characteristic genes were screened from these ferroptosis-related differential genes to construct the ferr.score model. The scoring model could accurately distinguish and predict the survival prognosis and immunotherapy efficacy in breast cancer patients. Conclusions: Ferroptosis plays an important role in the occurrence and development of tumors. According to the ferr.score model, the breast cancer samples can be divided into two groups with significantly different prognoses. These results provide novel insights and ideas for immunotherapy in breast cancer patients.

The nasal microbiome of predicting bronchopulmonary dysplasia in preterm infants.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease of prematurity and may cause substantial long-term disabilities. To characterize and compare the nasal swabs microbiome of early stage in premature infants and determine whether microbial diversity or composition in the nostrils associated with BPD disease. We performed a prospective observational cohort design. Preterm neonates less than or equal to 30 weeks of gestation were recruited from NICU, Children's Hospital, Zhejiang University School of Medicine from 2019 to 2020. Sterile foam swabs were collected from anterior nares at 1 and 3 weeks of postnatal age. We used PCR amplification and 16S rDNA sequencing. Neonatal demographic data including gestational age, birth weight, medication administration history and discharge outcomes were recorded. A total of 49 nasal swab samples were collected from 28 premature infants. Thirteen infants with BPD and 15 controls were finally involved in the study. Birth weights ranged from 700 to 1550 g. Gestational age ranged from 252/7 to 30. We found increased in the expression of Prevotella and decreased of Caulobacter in BPD group at both times. Prevotella and Caulobacter were correlated with the severity of BPD (Spearman r = 0.551, r = - 0.545; P = 0.00005, 0.00006; respectively). Receiver operating characteristic analysis showed that the area under characteristic curve of Caulobacter model at first week reached 0.821 and Prevotella model at third week was 0.796. Moreover, microbial functional prediction analysis revealed that ABC-type transports were distinctively changed in BPD group. In summary, the use of non-invasive nasal swabs of microbiome to explore the pathophysiology in BPD is a compelling method worthy continuing to expand and research.

Maternal Ureaplasma exposure during pregnancy and the risk of preterm birth and BPD: a meta-analysis.

PURPOSE: Perinatal Ureaplasma infection is associated with a variety of adverse outcomes and neonatal diseases. This meta-analysis is to evaluate current evidence evaluating the association between Ureaplasma and adverse pregnancy outcomes and bronchopulmonary dysplasia (BPD) in preterm infants. METHODS: We searched for published articles on Ureaplasma, preterm and BPD in PubMed, the Cochrane Library, and Embase databases posted before August 28, 2021. In addition, the references of these articles were screened. A random/fixed-effect model was used to synthesize predefined outcomes. RESULTS: A total of 19 cohort studies involving 11,990 pregnancy women met our inclusion criteria. Pregnancy Ureaplasma positive increased the risk of preterm birth [odds ratios (OR) 2.76, 95% confidence intervals (CI) 1.63-4.68], BPD (OR 2.39 95% CI 1.73-3.30), chorioamnionitis (OR 2.71, 95% CI 2.02-3.64) and premature rupture of membranes (PROM, OR 2.19, 95% CI 1.34-3.58). CONCLUSIONS: Pregnancy Ureaplasma positive may increase the risk of developing preterm birth, chorioamnionitis, PROM and BPD in the preterm infant. The evidence base is, however, of low quality and well-designed studies are needed.

[Stem cells for the treatment of Peyronie's disease].

Peyronie's disease (PD) is a connective tissue disorder characterized as fibrotic plaque localized in the tunica albuginea (TA), and its pathomechanism remains obscure. Endeavors are being made to explore effective and minimally invasive therapeutic strategies for PD, and some experimental studies have verified the preventative and therapeutic effects of stem cells (SC), especially adipose tissue-derived SCs (ADSC), on this disease and excavated some of their action mechanisms. Some scholars attempted the integration of SCs with graft tissues, aiming at the improvement of TA grafting and reconstruction. The only publicly available clinical trial of SC therapy for PD was encouraging, and further on-coming relevant researches are expected with simultaneous optimization of the scheme. In a word, the application of SCs in the prevention and treatment of PD is a promising topic for clinical research, and there remain quite a lot of unknowns to be explored. This article summarizes the existing researches in this field.

Long non-coding RNA HAGLROS regulates the proliferation, migration, and apoptosis of esophageal cancer cells via the HAGLROS-miR-206-NOTCH3 axis.

BACKGROUND: Esophageal cancer (EC) is a common malignant tumor of the digestive tract, the treatment of which involves surgery combined with radiotherapy and chemotherapy, as well as other comprehensive types of treatment. The pathogenesis of EC remains unclear, which hinders the development of clinical therapy and the identification of molecular targets for this disease. Long non-coding RNAs (lncRNAs) have been shown to be associated with the malignant biological behavior of EC, but the specific molecular mechanisms underlying the carcinogenesis of EC are not fully understood. METHODS: Reverse transcription-quantitative PCR (RT-qPCR) was applied to measure the lncRNA HAGLR opposite strand lncRNA (HAGLROS) levels in EC cell lines and tissues. Cell Counting Kit-8 (CCK-8) detection, scratch test, and Transwell assay were performed to determine the proliferation, migration and invasion of EC cell. The interaction between HAGLROS, microRNA (miR)-206, and notch receptor 3 (NOTCH3) was confirmed by RNA immunoprecipitation and dual luciferase reporter gene assays. RESULTS: HAGLROS is upregulated in esophageal squamous cell carcinoma (ESCC) tissues and predicts poor prognosis. Silent HAGLROS is negatively associated with malignant behavior in EC cells. Low expression of HAGLROS can induce decreased invasive and migratory abilities in EC cells. Downregulated HAGLROS significantly inhibits the proliferation of EC cells and accelerates apoptosis. HAGLROS promotes EC cell tumorigenesis in vivo. HAGLROS participates in the HAGLROS/miR-206/NOTCH3 regulatory axis in EC cells. CONCLUSIONS: HAGLROS may play a role in the progression of EC by modulating the miR-206/NOTCH3 signaling axis, and may be a novel target for the diagnosis and treatment of EC.

ADAMTS9-AS2: a potential diagnostic and prognostic hallmark in prostate cancer.

PURPOSE: To explore the expression level and prognostic value of ADAMTS9-AS2 in prostate cancer (PCa). METHODS: ADAMTS9-AS2 levels in 110 paired PCa tissues and adjacent normal tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between ADAMTS9-AS2 level and clinical parameters of PCa was analyzed. ROC (receiver operating characteristics) curves were depicted for assessing the diagnostic value of ADAMTS9-AS2 in PCa. Through collecting 5-year follow-up data of PCa patients, survival analysis was performed by Kaplan-Meier method. Finally, Cox regression model was used to analyze factors affecting outcomes of PCa patients. RESULTS: ADAMTS9-AS2 was downregulated in PCa tissues than in adjacent normal ones. Its level was lower in PCa tissues with clinical stage III+IV or tumor size ≥3cm compared to those with stage I+II or tumor size <3cm. ROC curves verified the diagnostic value of ADAMTS9-AS2 in PCa (AUC=0.902, cut-off value=0.40, sensitivity=90.00%, specificity=79.09%, Youden index=0.6909). Kaplan-Meier method and log-rank test uncovered worse prognosis in PCa patients expressing low level of ADAMTS9-AS2. Clinical stage, tumor size and ADAMTS9-AS2 level were independent factors influencing prognosis of PCa. CONCLUSIONS: ADAMTS9-AS2 is downregulated in PCa and its low level is unfavorable to the disease prognosis. ADAMTS9-AS2 may be utilized as a potential diagnostic and prognostic hallmark of PCa.

Ureteral polyps protruding from the urethra.

BACKGROUND: Ureteral fibro-epithelial polyp (UFP) is a rare benign ureteral tumor, and surgical removal of the polyps is still the preferred solution. Although many cases have reported polyps extending to the bladder, our case was the first to report a huge UFP that underwent endoscopic laser resection to highlight the urethra and cause severe end hematuria permanently. CASE PRESENTATION: In 2019, a 37-year-old woman came to the hospital because of hematuria and a dark red extraurethral mass. CTU inspection showed: filling defect between the right ureter and the bladder at the entrance of the bladder. After ureteroscopy, it was found that the ureteral mass came out of the urethral orifice. Then, under the direct view of the ureteroscope, a Ho:YAG laser was used to remove the tumor by cutting off along the its base, and the patient was discharged 3 days after the operation. CONCLUSION: Urethral polyps from the ureter should be considered in the differential diagnosis of urethral neoplasms. Ho:YAG laser resection under ureteroscopy is an effective option for treating UFP, but be careful of ureteral stricture after surgery.

Rapid antidepressant actions of imipramine potentiated by zinc through PKA-dependented regulation of mTOR and CREB signaling.

The slow onset of traditional antidepressants has become an urgent clinical issue, researchers are constantly exploring new antidepressants with prompt action. Previous studies have found that zinc levels were decreased in serum and brain of depressed patients or animal models. Zinc treatment can improve depressive symptoms and enhance the antidepressant effects of monoamine antidepressants. However, its mechanism of action is still unclear. This present study aims to investigate whether the zinc can enhance the rapid action of traditional antidepressant imipramine and to explore the potential mechanisms of action through the rapid antidepressant targets CREB (cAMP-response element binding protein) and mTOR (mammalian target of the rapamycin). Drug treatment included intraperitoneal injection of imipramine or zinc alone and imipramine plus zinc. Zinc had a rapid enhanced antidepressive effect on the imipramine and achieved a rapid antidepressant effect similar to ketamine. Combination of zinc with imipramine rapidly enhanced the phosphorylation of mTOR Ser2448 and CREB Ser133, and increased the expression of mTOR and CREB, which were dependent on the activation of PKA. In conclusion, combination therapy with zinc and monoamine antidepressants may overcome the problem of slow-onset action of traditional antidepressants in clinical uses.

Hypoxia preconditioned renal tubular epithelial cell-derived extracellular vesicles alleviate renal ischaemia-reperfusion injury mediated by the HIF-1α/Rab22 pathway and potentially affected by microRNAs.

We previously found that hypoxia induced renal tubular epithelial cells (RTECs) release functional extracellular vesicles (EVs), which mediate the protection of remote ischaemic preconditioning (RIPC) for kidney ischaemia-reperfusion (I/R) injury. We intend to investigate whether the EVs were regulated by hypoxia-inducible factor 1α (HIF-1α) and Rab22 during RIPC. We also attempted to determine the potentially protective cargo of the EVs and reveal their underlying mechanism. Hypoxia preconditioning (HPC) of human kidney 2 (HK2) cells was conducted at 1% oxygen (O2) for different amounts of time to simulate IPC in vitro. EVs were isolated and then quantified. HIF-1α- and Rab22-inhibited HK2 cells were used to investigate the role of the HIF-1α/Rab22 pathway in HPC-induced EV production. Both normoxic and HPC EVs were treated in vivo to assess the protective effect of I/R injury. Moreover, microRNA (miRNA) sequencing analysis and bioinformatics analysis was performed. We revealed that the optimal conditions for simulating IPC in vitro was no more than 12 h under the 1% O2 culture circumstance. HPC enhanced the production of EVs, and the production of EVs was regulated by the HIF-1α/Rab22 pathway during HPC. Moreover, HPC EVs were found to be more effective at attenuating mice renal I/R injury. Furthermore, 16 miRNAs were upregulated in HPC EVs. Functional and pathway analysis indicated that the miRNAs may participate in multiple processes and pathways by binding their targets to influence the biochemical results during RIPC. We demonstrated that HIF-1α/Rab22 pathway mediated RTEC-derived EVs during RIPC. The HPC EVs protected renal I/R injury potentially through differentially expressed miRNAs. Further study is needed to verify the effective EV-miRNAs and their underlying mechanism.

MiR-455-5p Suppresses the Progression of Prostate Cancer by Targeting CCR5.

Accumulated evidence indicates that miR-455-5p functions as tumor suppressor in the progression of various cancers. However, the mechanism through which miR-455-5p influences the tumorigenesis of human prostate cancer (PCa) remains undetermined. In this study, reanalysis of data obtained from the Memorial Sloan Kettering Cancer Center showed that miR-455-5p can be used as biomarker for PCa diagnosis and predictor of poor prognosis. Functional assays indicated that miR-455-5p overexpression could suppress cellular proliferation, inhibit tumor growth, and trigger apoptosis by activating and cleaving caspase 3. We experimentally verified that miR-455-5p negatively regulated the C-C motif chemokine receptor 5 (CCR5). Overall, our data demonstrate that miR-455-5p suppressed PCa cellular proliferation and induced cell apoptosis by downregulating CCR5. Thus, miR-455-5p may be considered a new therapeutic strategy for PCa.

Chemical Profiling of Lobelia chinensis with High-Performance Liquid Chromatography/Quadrupole Time-of-Flight Mass Spectrometry (HPLC/Q-TOF MS) Reveals Absence of Lobeline in the Herb.

Lobelia chinensis is a kind of herbal medicine widely distributed and used in Asia. The chemical components of this herb, however, have not been well studied until now. Lobeline, as an essential and famous bioactive compound in Lobelia genus, has been assumed to be present in L. chinensis. In order to ascertain its presence and, more importantly, proper use of this herb, chemical profiling this herb with highly sensitive and high-resolution analytical mass spectrometry was applied. In this study, high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC/Q-TOF MS) method was employed to systematically profile the chemical constituents of L. chinensis for the first time. Comparative chemical profiling study of L. chinensis and Lobelia inflata was also conducted to provide evidence whether lobeline is present or not. Piperidine alkaloids except for lobeline, alkaloid-lignan hybrids, flavonoids, polyacetylenes, nonanedioic acid, and some new phytochemicals were successfully identified in L. chinensis simultaneously. Comparing to the chemical profiles of L. inflata, lobeline was found to be absent in L. chinensis. All of the secondary metabolites in L. chinensis were determined with the HPLC/Q-TOF MS method. The absence of lobeline in L. chinensis was confirmed after this extensive study.

Integrated analysis of differentially expressed profiles and construction of a competing endogenous long non-coding RNA network in renal cell carcinoma.

BACKGROUND: Long non-coding RNAs (lncRNAs) play crucial roles in the initiation and progression of renal cell carcinoma (RCC) by competing in binding to miRNAs, and related competitive endogenous RNA (ceRNA) networks have been constructed in several cancers. However, the coexpression network has been poorly explored in RCC. METHODS: We collected RCC RNA expression profile data and relevant clinical features from The Cancer Genome Atlas (TCGA). A cluster analysis was explored to show different lncRNA expression patterns. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses and gene set enrichment analysis (GSEA) were performed to analyze the functions of the intersecting mRNAs. Targetscan and miRanda bioinformatics algorithms were used to predict potential relationships among RNAs. Univariate Cox proportional hazards regression was conducted to determine the RNA expression levels and survival times. RESULTS: Bioinformatics analysis revealed that the expression profiles of hundreds of aberrantly expressed lncRNAs, miRNAs, and mRNAs were significantly changed between different stages of tumors and non-tumor groups. By combining the data predicted by databases with intersection RNAs, a ceRNA network consisting of 106 lncRNAs, 26 miRNAs and 69 mRNAs was established. Additionally, a protein interaction network revealed the main hub nodes (VEGFA, NTRK2, DLG2, E2F2, MYB and RUNX1). Furthermore, 63 lncRNAs, four miRNAs and 31 mRNAs were significantly associated with overall survival. CONCLUSION: Our results identified cancer-specific lncRNAs and constructed a ceRNA network for RCC. A survival analysis related to the RNAs revealed candidate biomarkers for further study in RCC.

Knockdown of Ran GTPase expression inhibits the proliferation and migration of breast cancer cells.

Breast cancer is the second leading cause of cancer­associated mortality in women worldwide. Strong evidence has suggested that Ran, which is a small GTP binding protein involved in the transport of RNA and protein across the nucleus, may be a key cellular protein involved in the metastatic progression of cancer. The present study investigated Ran gene expression in breast cancer tissue samples obtained from 140 patients who had undergone surgical resection for breast cancer. Western blot analysis of Ran in breast cancer tissues and paired adjacent normal tissues showed that expression of Ran was significantly increased in breast cancer tissues. Immunohistochemistry analyses conducted on formalin­fixed paraffin­embedded breast cancer tissue sections revealed that Ran expression was associated with tumor histological grade, nerve invasion and metastasis, vascular metastasis and Ki­67 expression (a marker of cell proliferation). Kaplan­Meier survival analysis showed that increased Ran expression in patients with breast cancer was positively associated with a poor survival prognosis. Furthermore, in vitro experiments demonstrated that highly migratory MDA­MB­231 cancer cells treated with Ran­si­RNA (si­Ran), which knocked down expression of Ran, exhibited decreased motility in trans­well migration and wound healing assays. Cell cycle analysis of Ran knocked down MDA­MB­231 cells implicated Ran in cell cycle arrest and the inhibition of proliferation. Furthermore, a starvation and re­feeding (CCK­8) assay was performed, which indicated that Ran regulated breast cancer cell proliferation. Taken together, the results provide strong in vitro evidence of the involvement of Ran in the progression of breast cancer and suggest that it could have high potential as a therapeutic target and/or marker of disease.

[Predictive factors for clinically significant elevation of post-prostatectomy Gleason score in patients with biopsy Gleason score ≤7].

OBJECTIVE: To investigate the prognostic factors for clinically significant increase in post-prostatectomy Gleason score (pGS) in patients with biopsy Gleason score (bGS) ≤7. METHODS: This retrospective study included 170 cases of prostate cancer treated by radical prostatectomy in our hospital from January 2010 to December 2017. We analyzed the clinical and pathological data on the patients, including the age, preoperative serum tPSA, fPSA, fPSA / tPSA, prostate volume, PSA density (PSAD), and positive puncture rate of the patients with clinically significant elevation of pGS, as well as the possible factors for clinically significant pGS increase in patients with bGS = 7 and those with bGS ≤ 6. RESULTS: The pGS was found consistent with the bGS in 95 (55.9%) of the 170 patients, decreased in 11 (6.5%) and increased in 64 (37.6%). Among those with elevated pGS, 55 (32.4%) were shown with and the other 9 (5.3%) without clinical significance. Clinically significant escalation of pGS was markedly correlated with the positive puncture rate in the patients with bGS = 7 (P = 0.021) and with the age (P = 0.018) and PSAD (P = 0.033) of those with bGS ≤ 6. ROC curve analysis further showed the positive puncture rate > 0.528 in the patients with bGS = 7 and a higher risk of clinically significant pGS increase in those aged > 64.5 years with bGS ≤ 6 and PSAD > 0.267 µg/(L·g). CONCLUSIONS: Clinically significant elevation of pGS is correlated with the rate of positive punctures in prostate cancer patients with bGS = 7 and with age and PSAD in those with bGS ≤ 6.