Molecular targets and mechanisms of different aberrant alternative splicing in metastatic liver cancer

Metastasis remains a major challenge in the successful management of malignant diseases.The liver is a major site of metastatic disease and a leading cause of death from gastrointestinal malignancies such as colon,stomach,and pancreatic cancers,as well as melanoma,breast cancer,and sarcoma.As an important factor that influences the development of metastatic liver cancer,alternative splicing drives the diversity of RNA transcripts and protein subtypes,which may provide potential to broaden the target space.In particular,the dysfunction of splicing factors and abnormal expression of splicing variants are associated with the occurrence,progression,aggressiveness,and drug resistance of cancers caused by the selective splicing of specific genes.This review is the first to provide a detailed summary of the normal splicing process and alterations that occur during metastatic liver cancer.It will cover the role of alternative splicing in the mechanisms of metastatic liver cancer by examining splicing factor changes,abnormal splicing,and the contribution of hypoxia to these changes during metastasis.

Conceptual Analysis of Self-Management in Patients with Hypertension

Objective:To clarify the concept of self-management in hypertensive patients by analyzing the definition,attributes,and measurement tools through a literature review.Methods:An Internet-based search of the databases was conducted using Academic Search Complete,Medical Line,CINAHL,Health Source:Nursing/Scholarly Edition,and Google Scholar.In the search process,keywords or free text were combined by using Boolean operators,with the search terms“self of management”or“self-management,”“concept*analysis”or“concept*definition,”and Walker and Avant’s concept analysis method was used.Results:Analysis of relevant literature summarized the conceptual attributes of self-management in hypertensive patients as the active participation of patients in the treatment process;the presence of interaction provided by patients and health care providers;the use of certain health management tools;and the aim of maintaining and improving the health status and living capacity of hypertensive patients.Conclusion:The concept of self-management for hypertensive patients was clarified,which helps to promote the application of hypertensive self-management in clinical work and improve outcomes and quality of life for patients with hypertension.

The necessity and possibility of implementation of nurse prescribing in China: An international perspective

Background:The number of countries where nurses are legally permitted to prescribe has grown rapidly due to a variety of external and internal forces.Despite its international popularity,nurse prescribing has not yet been implemented in China widely.Objective:The intent of this paper is to review the current international literature regarding nurse prescribing so as to explore the necessity and possibility of implementation of nurse prescribing in China and classify the research gap.Methods:Eight electronic databases including Embase,SpringerLink,EBSCO,CINAHL,Medline,Wiley,Science Direct,CochraneLibrary were electronically searched to identify related peer-review articles published in the English language only from 2007 to 2017.Relative references found from the identified studies were traced back to ensure that potentially eligible articles were included.Results:Thirty-three publications which met the inclusion criteria were included in this literature review.The literature shows that not only could nurse prescribing provide quicker service,improvements in quality,but also could make better utilization of the nurses' professional skills and increase nurses' autonomy.Moreover,the barriers of nurse prescribing are explored to identify the factors that may facilitate the success of its implementation.Conclusion:The review advises that nurses' views towards nurse prescribing have played a significant role in the success of nurse prescribing.While no literature regarding Chinese nurses' attitudes towards nurse prescribing could be identified,it is imperative to examine their attitudes on it.This would help Chinese healthcare policymakers ascertain the necessity of the introduction of nurse prescribing and provide them with valuable information for service planning.

Daptomycin and linezolid for severe methicillin-resistant Staphylococcus aureus psoas abscess and bacteremia:A case report and review of the literature

BACKGROUND Vancomycin remains a first-line treatment drug as per the treatment guidelines for methicillin-resistant Staphylococcus aureus(MRSA)bacteremia.However,a number of gram-positive cocci have developed resistance to several drugs,including glycopeptides.Therefore,there is an urgent need for effective and innovative antibacterial drugs to treat patients with infections caused by drugresistant bacteria.CASE SUMMARY A 24-year-old male was admitted to hospital owing to lumbago,fever,and hematuria.Computed tomography(CT)results showed an abscess in the psoas major muscle of the patient.Repeated abscess drainage and blood culture suggested MRSA,and vancomycin was initiated.However,after day 10,CT scans showed abscesses in the lungs and legs of the patient.Therefore,treatment was switched to daptomycin.Linezolid was also added considering inflammation in the lungs.After 10 d of the dual-drug anti-MRSA treatment,culture of the abscess drainage turned negative for MRSA.On day 28,the patient was discharged without any complications.CONCLUSION This case indicates that daptomycin combined with linezolid is an effective remedy for bacteremia caused by MRSA with pulmonary complications.

Follicular carcinoma of the thyroid with a single metastatic lesion in the lumbar spine:A case report

BACKGROUND The bone is the second most common site of thyroid cancer metastasis,after the lung.Treatment options for bone metastasis of thyroid cancer include surgery,radioiodine therapy(RAIT),external radiation therapy,thyroid-stimulating hormone(TSH)inhibition,bisphosphonates,and small-molecule targeted therapies.In most cases,thyroid carcinoma is found in the thyroid tissue;reports of follicular thyroid carcinoma with a single metastasis to the lumbar spine are rare.CASE SUMMARY We report a case of bone metastasis as the only clinical manifestation of thyroid cancer.The patient was a 67-year-old woman with lumbar pain for 7 years and aggravation with intermittent claudication who had previously undergone partial thyroidectomy of a benign thyroid lesion.No abnormal nodules were found in the bilateral thyroid glands.However,imaging studies were consistent with a spinal tumor,and the lesion was diagnosed as a metastatic follicular carcinoma of thyroid origin.We adopted a multidisciplinary collaboration and comprehensive treatment approach.The patient underwent lumbar spine surgery,total resection of the thyroid,postoperative TSH suppression therapy,and RAIT.There were no complications associated with the operation,and the patient had good postoperative recovery.She has experienced no recurrence.CONCLUSION Follicular thyroid carcinoma is associated with early hematogenous metastasis,and the bone is a typical site of metastasis.Single bone metastasis is not a contraindication to medical procedures,and providing the appropriate therapy can result in better outcomes and quality of life for these patients.

Expression and significance of vascular endothelial growth factor D in gastric cancer

Objective: To investigate the expression of vascular endothelial growth factor D (VEGF-D) in gastric cancer and its relationship with lymph node metastasis. Methods: 100 cases of gastric carcinoma tissues (50 cases with lymph node metastasis, 50 cases negative) and 30 cases of normal gastric tissues were gathered to detect the expressions of VEGF-C and D proteins by immunohistochemistry. Results: VEGF-C and D were revealed in cytoplasm of gastric carcinoma tissues and normal gastric tissues. The positive rates of VEGF-C and D expressions were significantly higher in gastric cancer tissues than those in the normal ones (51%, 60% vs 10%, 20% respectively; both P < 0.05). There were significant correlations be- tween the positive expression of VEGF-D and lymph node metastasis, lymphatic invasion, positive expression of VEGF-C, but not with tumour size, tissue differentiation, and venous invasion. Conclusion: The expression of VEGF-D is closely related to lymph node metastasis in gastric carcinoma.

A systematic review of the effect of mobile health on cardiac rehabilitation among coronary heart disease patients

Objective： Mobile health （mHealth） provides an innovative and effective approach to promote prevention and management of coronary heart disease. However, the magnitude of its effects is unclear. The aim of this systematic review was to examine the impact of mHealth-based cardiac rehabilitation outcomes among coronary heart disease patients. Methods： Medline, CINAHL, Embase, PubMed, Google Scholar, NICE, and Cochrane library were searched for randomized controlled trials published between January 2002 and March 2017 which compared mHealth with conventional cardiac rehabilitation programs among coronary heart disease patients. Results： Eight articles were included in this review. The impact of mHealth interventions on physical activity, medicine adherence, smoking cessation, level of anxiety, and quality of life was inconsistent among the articles. Conclusions： Further research is needed to conclusively determine the impact of mHealth interventions on cardiac rehabilitation outcomes. The limitations of the included studies （e.g., inadequate sample size, failure to address the core components of cardiac rehabilitation programs, and lack of theory-based design） should be taken into account when designing future studies.

The Evaluation Characteristics of Type B Aortic Intramural Hematoma and Ten Years Treatment Outcomes

Background: Type B aortic intramural hematoma (IMH-B) is recognized as a subset of aortic dissection. The evolution of uncomplicated IMH-B is very difficult to predict. How and when to deal with this disease is unclear. The present study constructed two models to explore this problem. One is the morphology evolution model, which explored the risk factors and predictors for the IMH-B patients. Another is the predictive model confirmed the predictors and the time for invasive treatment of uncomplicated IMH-B patients. Objective: To explore the evolution predictors and detect the time for invasive treatment of uncomplicated IMH-B patients. Methods: Themorphology evolution model demonstrated that all 81 patients were diagnosis with CTA images. The initial and follow-up data were retrospectively studied. The evolution data were collection and measurement from initial and follow-up CTA images data. The predictive model showed that predictors of progression were detected with cox regression analysis. Results: All 81IMH-B patients were followed-up ranged from 1.2 to 36 months (median, 22 months). 26 patients accepted invasive treatment (24 underwent TEVAR and 2 underwent Surgery). 55 patients received medical treatment. Invasive treatment (IT) group overall events are 1/26 (3.8%); medical treatment (MT) group overall events are 33/55 (60.0%); IT group vs. MT group: p < 0.001. Moreover, we found that most events related aorta occurred within 30 days. Multivariate Cox regression analysis MDAD (hazard ratio, 3.58;95% CI, 1.25- 5.78;p < 0.001), MDAHT (hazard ratio, 4.26;95% CI, 0.85 - 7.84;p < 0.001), and IMH with PAU (hazard ratio, 3.58;95% CI, 1.02 - 5.63;p < 0.001) were confirmed as the independent predictors. Conclusions: MDAD > 45 mm, MDAHT > 10 mm, and IMH with PAU may be the important predictors for uncomplicated IMH-B patients. Most adverse aorta related events occurred within 30 days. It would be careful follow-up, closely observe for these patients within 30 days, and take necessary treatment strategies in time.

Adherence-A concept analysis in the context of cardiac rehabilitation

Objective： To explore and identify the concept of adherence in the context of cardiac rehabilitation. This conceptanalysis will provide a framework for clinical decision-making and intervention to improve patients’ adherence tocardiac rehabilitation programme. Method： Walker and Avant’s framework was used to analysis the concept ofadherence. Results： Adherence is defined as patients collaboration with health care provider, active involvement in thetreatment regimen, and persistence in practice characterized by self-efficacy and relapse-prevention. Defining Attributesof adherence include collaboration relationship; self-efficacy promotion and relapse-prevention. Antecedents ofadherence include health care provider’s prescription, illness perceptions, social-economic and environmental factors.Patients adherence to cardiac rehabilitation programme can improve clinical outcomes. However, there is no standardinstrument to measure adherence. Conclusion： Based on the concept analysis, in order to improve patients’ adherence tocardiac rehabilitation, health care provider should invite patients active involvement in making rehabilitation plan andpromote patients’ self-efficacy and prevention relapse.

小鼠整胚石蜡切片制备方法的改进

Objective:The morphology analysis of whole-mount mouse embryos was observed using an improved paraffin section technique.Methods:Mouse embryos of varying embryonic ages were collected and whole-mount embryo paraffin sections were prepared using PFA-intravenously injected fixation,prolonged dehydration,and paraffin embedding.Hematoxylin and eosin(H&E)staining and immunohistochemical staining were employed to evaluate the quality of sections,with different tissues being observed labeled by CD34.Results:Following a series of tissue processing and staining procedures,the structure of the whole-mount mouse embryo was well-preserved,and the staining was clear and easily distinguishable.Embryos of different embryonic ages were treated differently,yet the quality of tissue processing remained highly consistent.Conclusion:Tissue processing and staining have been significantly improved,allowing for the easy acquisition of whole-mount mouse embryos of different ages through simplified methods of tissue fixation and dehydration duration.The staining results are clear and stable,providing technical support for the study of mouse embryo development.

Optimal concentration of necrostatin-1 for protecting against hippocampal neuronal damage in mice with status epilepticus

Hippocampal neurons undergo various forms of cell death after status epilepticus.Necrostatin-1 specifically inhibits necroptosis mediated by receptor interacting protein kinase 1 (RIP1) and RIP3 receptors.However,there are no reports of necroptosis in mouse models of status epilepticus.Therefore,in this study,we investigated the effects of necrostatin-1 on hippocampal neurons in mice with status epilepticus,and,furthermore,we tested different amounts of the compound to identify the optimal concentration for inhibiting necroptosis and apoptosis.A mouse model of status epilepticus was produced by intraperitoneal injection of kainic acid,12 mg/kg.Different concentrations of necrostatin- 1 (10,20,40,and 80 μM) were administered into the lateral ventricle 15 minutes before kainic acid injection.Hippocampal damage was assessed by hematoxylin-eosin staining 24 hours after the model was successfully produced.Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining,western blot assay and immunohistochemistry were used to evaluate the expression of apoptosis-related and necroptosis-related proteins.Necrostatin-1 alleviated damage to hippocampal tissue in the mouse model of epilepsy.The 40 μM concentration of necrostatin-1 significantly decreased the number of apoptotic cells in the hippocampal CA1 region.Furthermore,necrostatin-1 significantly downregulated necroptosis-related proteins (MLKL,RIP1,and RIP3) and apoptosis-related proteins (cleaved-Caspase-3,Bax),and it upregulated the expression of anti-apoptotic protein Bcl-2.Taken together,our findings show that necrostatin-1 effectively inhibits necroptosis and apoptosis in mice with status epilepticus,with the 40 μM concentration of the compound having an optimal effect.The experiments were approved by the Animal Ethics Committee of Fujian Medical University,China (approval No.2016-032) on November 9,2016.

Volumetric modulation arc radiotherapy with flattening filter-free beams compared with conventional beams for nasopharyngeal carcinoma:a feasibility study

There is increasing interest in the clinical use of flattening filter-free(FFF) beams.In this study,we aimed to investigate the dosimetric characteristics of volumetric modulated arc radiotherapy(VMAT) with FFF beams for nasopharyngeal carcinoma(NPC).Ten NPC patients were randomly selected to undergo a RapidArc plan with either FFF beams(RA-FFF) or conventional beams(RA-C).The doses to the planning target volumes(PTVs),organs at risk(OARs),and normal tissues were compared.The technical delivery parameters for RapidArc plans were also assessed to compare the characteristics of FFF and conventional beams.Both techniques delivered adequate doses to PTVs.For PTVs,RA-C delivered lower maximum and mean doses and improved conformity and homogeneity compared with RA-FFF.Both techniques provided similar maximum doses to the optic nerves and lenses.For the brain stem,spinal cord,larynx,parotid glands,oral cavity,and skin,RA-FFF showed significant dose increases compared to RA-C.The dose to normal tissue was lower in RA-FFF.The monitor units(MUs) were(536 ± 46) MU for RA-FFF and(501± 25) MU for RA-C.The treatment duration did not significantly differbetween plans.Although both treatment plans could meet clinical needs,RA-C is dosimetrically superior to RA-FFF for NPC radiotherapy.

Association of hypoxia-inducible factor-1α (HIF1α) 1772C/T genepolymorphism with susceptibility to renal cell carcinoma/prostatecancer

In this study,we used a meta-analysis method to evaluate the relationship between hypoxia-inducible factor-1α(HIF1α)1772C/T gene polymorphism(rs 11549465)and renal cell carcinoma(RCC)/prostate cancer risk.We searched for relevant studies(before March 1,2019)on Cochrane Library,Embase,and PubMed.Studies meeting the inclusion criteria were recruited into this meta-analysis.The outcome of dichotomous data was showed in the way of odds ratios(OR),and 95%confidence intervals(CI)were also counted.In this investigation,there was no association between HIF1α1772C/T gene polymorphism and susceptibility to RCC in Caucasians,Asians as well as overall populations.In addition,HIF1α1772C/T gene polymorphism was not found to be relevant to the survival in RCC.Interestingly,the T allele was relevant to prostate cancer risk in all populations,but not in Caucasians and Asians.However,the TT genotype and the CC genotype were not related to prostate cancer susceptibility in Asian,Caucasian,and all populations.In conclusion,the T allele of the HIF1α1772C/T gene polymorphism was related to prostate cancer risk in the overall populations.

Individualized treatment of breast cancer with chronic renal failure: A case report and review of literature

BACKGROUND Studies have shown that patients with chronic renal failure(CRF)are more likely to suffer from breast cancer and other malignant tumors.To our knowledge,CRF can reduce drug excretion,thereby increase drug exposure and lead to increased toxicity,which will limit drug treatment and lead to tumor progression.Currently,there are few successful reports on the combination of docetaxel,trastuzumab,and pertuzumab(THP)as a neoadjuvant treatment regimen for breast cancer patients with CRF.CASE SUMMARY We report a breast cancer(cT2N2M0,Her-2+/HR-)patient with CRF.It was a clinical stage IIIA tumor on the left breast.The patient had suffered from uremia for 2 years,and her heart function was normal.Based on the pathological type,molecular type,and clinical stage of breast cancer,and the patient’s renal function,the clinician analyzed the pharmacological and pharmacokinetic characteristics of the antitumor drugs after consulting the relevant literature,and prescribed the neoadjuvant regimen of THP(docetaxel 80 mg/m²,trastuzumab 8 mg/kg for the first dose,and 6 mg/kg for the maintenance dose with pertuzumab 840 mg for the first dose and 420 mg for the maintenance dose),once every 3 wk,for a total of 6 courses.The neoadjuvant treatment had a good effect,and the patient then underwent surgery which was uneventful.CONCLUSION CRF is not a contraindication for systemic treatment and surgery of breast cancer.The THP regimen without dose adjustment may be a safe and effective neoadjuvant treatment for HER-2 positive breast cancer patients with CRF.

Comment of Walker and Avant’s method of concept analysis

In order to promote the nursing discipline to developindependently and scientifically, nursing practice shouldbe guided by nursing theory instead of intuition andexperience of nurses [1]. Nursing theory can assist nursesto deliver individual patient’s care and help to improveobservation and recognition of specific patient need, be itbiological, psychological or social [2]. Nursing theory hasdeveloped quickly and successfully in recent decadesinternationally; however, it is still in the early stage ofdevelopment in China.

Effects of Continuous Sciatic Nerve Block by Tetrodotoxin on Growth Associated Protein-43 Expression in Dorsal Root Ganglions of Normal and Sciatic Nerve Injury Rats

Growth associated protein-43 （GAP-43） is considered to be one of the most useful molecular markers for the neural development, nerve regeneration, and neuroplasticity. In most mature neurons, the expression of GAP-43 is at very low or negative level; its expression is triggered in response to the interruption of axonal transport. The purpose of this study was to examine whether continuous sciatic nerve block by tetrodotoxin （TTX） affects GAP-43 expression in the dorsal root ganglion （DRG） of normal and sciatic nerve injury rats.

Click-hydrogel delivered aggregation-induced emissive nanovesicles for simultaneous remodeling and antibiosis of deep burn wounds

As a high-risk trauma,deep burns are always hindered in their repair process by decreased tissue regeneration capacity and persistent infections.In this study,we developed a simultaneous strategy for deep burn wounds treatment using functional nanovesicles with antibacterial and tissue remodeling properties,delivered via a click-chemistry hydrogel.An aggregation-induced emission photosensitizer of 4-(2-(5-(4-(diphenylamino)phenyl)thiophen-2-yl)vinyl)-1-(2-hydroxyethyl)pyridin-1-ium bromide(THB)with excellent photodynamic properties was first prepared,and then combined with readily accessible adipose stem cells-derived nanovesicles to generate the THB functionalized nanovesicles(THB@ANVs).The THB@ANVs showed strong antibacterial activity against Gram-positive bacteria(up to 100%killing rate),and also beneficial effects on tissue remodeling,including promoting cell migration,cell proliferation,and regulating immunity.In addition,we prepared a click-hydrogel of carboxymethyl chitosan for effective delivery of THB@ANVs on wounds.This hydrogel could be injected to conform to the wound morphology while responding to the acidic microenvironment.In vivo evaluations of wound healing revealed that the THB@ANVs hydrogel dressing efficiently accelerated the healing of second-degree burn wounds by reducing bacterial growth,regulating inflammation,promoting early angiogenesis,and collagen deposition.This study provides a promising candidate of wound dressing with diverse functions for deep burn wound repair.

Genome-wide expression profiling of the response to terbinafine in Candida albicans using a cDNA microarray analysis

Background Candida albicans is the most frequently seen opportunistic human fungal pathogen. Terbinafine is an allylamine antifungal agent that has been proven to have high clinical efficacy in the therapy of fungal infections, the mechanism of action of terbinafine involves the specific inhibition of fungal squalene epoxidase, resulting in ergosterol deficiency and accumulation of intracellular squalene. We used cDNA microarray analysis technology to monitor global expression profile changes of Candida albicans genes in response to terbinafine treatment, and we anticipated a panoramic view of the responses of Candida albicans cells to the representatives of allylamine antifungal agents at the molecular level in an effort to identify drug class-specific and mechanism-independent changes in gene expression.Methods Candida albicans strain ATCC 90028 was exposed to either medium alone or terbinafine at a concentration equivalent to the 1/2 minimal inhibitory concentrations （MICs, 4 mg/L） for 90 minutes. RNA was isolated and gene expression profiles were compared to identify the changes in the gene expression profile using a cDNA microarray analysis. Differential expression of 10 select genes detected by cDNA microarray analysis was confirmed by semi-quantitative reverse transcription-polymerase chain reaction （RT-PCR）. Results A total of 222 genes were found to be responsive to terbinafine, including 121 up-regulated genes and 101 down-regulated genes. These included genes encoding membrane transport proteins belonging to the members of the ATP-binding cassette （ABC） or major facilitator supeffamily （MFS; CDR1, AGP2, GAP6, PHO84, HOL3, FCY23, VCX1）, genes involved in stress response and detoxification （CDR1, AGP2, HOL3）, and gene involved in the ergosterol biosynthesis pathway （ERG12）. The results of semi-quantitative RT-PCR were consistent with that of the cDNA microarray analysis. Conclusions The up-regulation of the gene encoding the multidrug resistance efflux pump CDR1 may contribute to the terbinafine resistance in Candida albicans. However, the precise roles of other affected genes remain unclear, further studies of these genes and their respective products that play roles in the context of antifunqal resistance are warranted.

Healthy individuals vs patients with bipolar or unipolar depression in gray matter volume

BACKGROUND Previous studies using voxel-based morphometry(VBM)revealed changes in gray matter volume(GMV)of patients with depression,but the differences between patients with bipolar disorder(BD)and unipolar depression(UD)are less known.AIM To analyze the whole-brain GMV data of patients with untreated UD and BD compared with healthy controls.METHODS Fourteen patients with BD and 20 with UD were recruited from the Mental Health Center of Shantou University between August 2014 and July 2015,and 20 nondepressive controls were recruited.After routine three-plane positioning,axial T2WI scanning was performed.The connecting line between the anterior and posterior commissures was used as the scanning baseline.The scanning range extended from the cranial apex to the foramen magnum.Categorical data are presented as frequencies and were analyzed using the Fisher exact test.RESULTS There were no significant intergroup differences in gender,age,or years of education.Disease course,age at the first episode,and Hamilton depression rating scale scores were similar between patients with UD and those with BD.Compared with the non-depressive controls,patients with BD showed smaller GMVs in the right inferior temporal gyrus,left middle temporal gyrus,right middle occipital gyrus,and right superior parietal gyrus and larger GMVs in the midbrain,left superior frontal gyrus,and right cerebellum.In contrast,UD patients showed smaller GMVs than the controls in the right fusiform gyrus,left inferior occipital gyrus,left paracentral lobule,right superior and inferior temporal gyri,and the right posterior lobe of the cerebellum,and larger GMVs than the controls in the left posterior central gyrus and left middle frontal gyrus.There was no difference in GMV between patients with BD and UD.CONCLUSION Using VBM,the present study revealed that patients with UD and BD have different patterns of changes in GMV when compared with healthy controls.