Ultrasound in Ti-Rads Classification of Thyroid Nodules at the Marie Curie Medical Clinic

Introduction: A thyroid nodule is a localized hypertrophy within the thyroid parenchyma. The aim of our study was to study the benefit of ultrasound in the Ti-rads classification of thyroid nodules. Methodology: This was a prospective study with a descriptive aim, with prospective collection, which took place over a period of 17 months at the “Marie Curie” medical clinic. The ultrasound machine used was a Voluson E8 from 2011 and the examinations were carried out by two radiologists and two experienced sonographers. The parameters studied were sociodemographic data;clinical data and ultrasound aspects of the Ti-rads classification in the management of nodules. Results: We collected 235 patients out of 738 patients referred to the service for a cervical ultrasound, i.e. a frequency of 31.84% of cases. There was a female predominance with 95.7% of cases and a sex ratio of 0.04. The average age of our patients was 50 years. We found on cervical ultrasound: Isthmo-lobar glandular hyperplasia in 99 patients, i.e. a frequency of 42.1%. The Ti-rads 3 classification was the most represented in 69.4% of cases. The benignity criterion represented 85.6% of cases in our patients and the malignancy criterion represented 14.4% of cases. Conclusion: The precise description of a thyroid nodule provided by ultrasound (Ti-rads) is essential in the management of nodules.

Chronic hepatitis C:Treat or wait? Medical decision making in clinical practice

AIM:To analyzes the decision whether patients with chronic hepatitis C virus (HCV) infection are treated or not.METHODS:This prospective cohort study included 7658 untreated patients and 6341 patients receiving pegylated interferon α2 a/ribavirin,involving 434 physicians/institutions throughout Germany (377 in private practice and 57 in hospital settings).A structured questionnaire had to be answered prior to the treatment decision,which included demographic data,information about the personal life situation of the patients,anamnesis and symptomatology of hepatitis C,virological data,laboratory data and data on concomitant diseases.A second part of the study analyzes patients treated with pegylated interferon α2a.All questionnaires included reasons against treatment mentioned by the physician.RESULTS:Overall treatment uptake was 45%.By multivariate analysis,genotype 1/4/5/6,HCV-RNA ≤ 520 000 IU/mL,normal alanine aminotransferase (ALT),platelets ≤ 142 500/μL,age > 56 years,female gender,infection length > 12.5 years,concomitant diseases,human immunodeficiency virus co-infection,liver biopsy not performed,care in private practice,asymptomatic disease,and unemployment were factors associated with reduced treatment rate.Treatment and sustained viral response rates in migrants (1/3 of cohort) were higher than in German natives although 1/3 of migrants had language problems.Treatment rate and liver biopsy were higher in clinical settings when compared to private practice and were low when ALT and HCV-RNA were low.CONCLUSION:Some reasons against treatment were medically based whereas others were related to fears,socio-economical problems,and information deficits both on the side of physicians and patients.

A Study on the Public Awareness of Hierarchical Medical System in Taiwan

The purpose of hierarchical medical system is to lead in terms of improving efficiency, differentiating healthcare services and promoting labor division by changing the healthcare seeking behavior. The purpose of this research aims to discuss the public awareness of hierarchical medical system in Taiwan for the reference of health policy makers. We obtained our research data using a questionnaire survey;the total number of qualified patients was 1340. This research finds that more subjects agreed to the hierarchical medical system and medical referral system, but many people still disagreed with changes to their healthcare seeking choices due to policy promotion. Subtle changes, therefore, are observed that imply a crisis in terms of the trust in healthcare. The healthcare seeking behavior will not change if there is a difference between the medical awareness of patients and policy implementation, and the government needs to be concerned with this result when making policies.

Diabetic retinopathy:A review on its pathophysiology and novel treatment modalities

Diabetes mellitus(DM)is a chronic metabolic non-communicable disease with the ability to cause serious microvascular and macrovascular complications throughout the body,including in the eye.Diabetic retinopathy(DR),present in onethird of patients with diabetes,is a vision-threatening complication caused by uncontrolled diabetes,which greatly affects the retinal blood vessels and the lightsensitive inner retina,eventually leading to blindness.Several epidemiological studies elucidate that DR can vary by age of onset,duration,types of diabetes,and ethnicity.Recent studies show that the pathogenesis of diabetic retinopathy has spread its roots beyond merely being the result of hyperglycemia.The complexity of its etiopathology and diagnosis makes therapeutic intervention challenging.This review throws light on the pathological processes behind DR,the cascade of events that follow it,as well as the available and emerging treatment options.

Effects of pulmonary surfactant combined with noninvasive positive pressure ventilation in neonates with respiratory distress syndrome

BACKGROUND Neonatal respiratory distress syndrome(NRDS)is one of the most common diseases in neonatal intensive care units,with an incidence rate of about 7%among infants.Additionally,it is a leading cause of neonatal death in hospitals in China.The main mechanism of the disease is hypoxemia and hypercapnia caused by lack of surfactant AIM To explore the effect of pulmonary surfactant(PS)combined with noninvasive positive pressure ventilation on keratin-14(KRT-14)and endothelin-1(ET-1)levels in peripheral blood and the effectiveness in treating NRDS.METHODS Altogether 137 neonates with respiratory distress syndrome treated in our hospital from April 2019 to July 2021 were included.Of these,64 control cases were treated with noninvasive positive pressure ventilation and 73 observation cases were treated with PS combined with noninvasive positive pressure ventilation.The expression of KRT-14 and ET-1 in the two groups was compared.The deaths,complications,and PaO_(2),PaCO_(2),and PaO_(2)/FiO_(2)blood gas indexes in the two groups were compared.Receiver operating characteristic curve(ROC)analysis was used to determine the diagnostic value of KRT-14 and ET-1 in the treatment of NRDS.RESULTS The observation group had a significantly higher effectiveness rate than the control group.There was no significant difference between the two groups in terms of neonatal mortality and adverse reactions,such as bronchial dysplasia,cyanosis,and shortness of breath.After treatment,the levels of PaO_(2)and PaO_(2)/FiO_(2)in both groups were significantly higher than before treatment,while the level of PaCO_(2)was significantly lower.After treatment,the observation group had significantly higher levels of PaO_(2)and PaO_(2)/FiO_(2)than the control group,while PaCO_(2)was notably lower in the observation group.After treatment,the KRT-14 and ET-1 levels in both groups were significantly decreased compared with the pre-treatment levels.The observation group had a reduction of KRT-14 and ET-1 levels than the control group.ROC curve analysis showed that the area under the curve(AUC)of KRT-14 was 0.791,and the AUC of ET-1 was 0.816.CONCLUSION Combining PS with noninvasive positive pressure ventilation significantly improved the effectiveness of NRDS therapy.KRT-14 and ET-1 levels may have potential as therapeutic and diagnostic indicators.

Happiness and harmony through health culture diplomacy as integrative maternal-child health nursing

For this editorial,our colleague Dr.Naeema Hasan Al Qasseer,former World Health Organization(WHO)Senior Scientist of Nursing and Midwifery joins me to add her wisdom and experience on the topic of integrative maternal-child health nursing.

Identification and Validation of Novel Biomarkers Related to the Calcium Metabolism Pathway in Hypertension Patients Based on Comprehensive Bioinformatics Methods

Background: Hypertension is a universal risk factor for cardiovascular diseases and is thus the leading cause of death worldwide. The identification of novel prognostic and pathogenesis biomarkers plays a key role in disease management. Methods: The GSE145854 and GSE164494 datasets were downloaded from the Gene Expression Omnibus (GEO) database and used for screening and validating hypertension signature genes, respectively. Gene Ontology (GO) enrichment analysis was performed on the differentially expressed genes (DEGs) related to calcium ion metabolism in patients with hypertension. The core genes related to immune infiltration were analyzed and screened, and the activity of the signature genes and related pathways was quantified using gene set enrichment analysis (GSEA). The infiltration of immune cells in the blood samples was analyzed, and the DEGs that were abnormally expressed in the clinical blood samples of patients with hypertension were verified via RT-qPCR. Results: A total of 176 DEGs were screened. GO showed that DEGs was involved in the regulation of calcium ion metabolism in biological processes (BP), actin mediated cell contraction, negative regulation of cell movement, and calcium ion transmembrane transport, and in the regulation of protease activity in molecular functions (MF). KEGG analysis revealed that the DEGs were involved mainly in the cGMP-PKG signaling pathway, ubiquitin-protein transferase, tight junction-associated proteins, and the regulation of myocardial cells. MF analysis revealed the immune infiltration function of the cells. RT-qPCR revealed that the expression of Cacna1d, Serpine1, Slc8a3, and Trpc4 was up regulated in hypertension, the expression of Myoz2 and Slc25a23 was down regulated. Conclusion: Cacna1d, Serpine1, Slc8a3, Trpc4, Myoz2 and Slc25a23 may be involved in the regulation of calcium metabolism pathways and play key roles in hypertension. These differentially expressed calcium metabolism-related genes may serve as prognostic markers of hypertension.

Identification and Validation of Vascular-Associated Biomarkers for the Prognosis and Potential Pathogenesis of Hypertension Using Comprehensive Bioinformatics Methods

Background: Hypertension, also known as increased blood pressure, is a phenomenon in which blood flows in blood vessels and causes persistently higher-than-normal pressure on the vessel wall. The identification of novel prognostic and pathogenesis biomarkers plays a key role in the management of hypertension. Methods: The GSE7483 and GSE75815 datasets from the gene expression omnibus (GEO) database were used to identify the genes associated with hypertension that were differentially expressed genes (DEGs). The functional role of the DEGs was elucidated by gene body (GO) enrichment analysis. In addition, we performed an immune infiltration assay and GSEA on the DEGs of hypertensive patients and verified the expression of novel DEGs in the blood of hypertensive patients by RT-qPCR. Results: A total of 267 DEGs were identified from the GEO database. GO analysis revealed that these genes were associated mainly with biological processes such as fibroblast proliferation, cell structural organization, extracellular matrix organization, vasculature development regulation, and angiogenesis. We identified five possible biomarkers, Ecm1, Sparc, Sphk1, Thbsl, and Mecp2, which correlate with vascular development and angiogenesis characteristic of hypertension by bioinformatics, and explored the clinical expression levels of these genes by RT-qPCR, and found that Sparc, Sphk1, and Thbs1 showed significant up-regulation, in agreement with the results of the bioinformatics analysis. Conclusion: Our study suggested that Sparc, Sphk1 and Thbs1 may be potential novel biomarkers for the diagnosis, treatment and prognosis of hypertension and that they are involved in the regulation of vascular development and angiogenesis in hypertension.

New Ideas in Narrative Practice for Mind and Body Healing

To enrich the specific methods of narrative clinical practice in Chinese medicine and stimulate the innovation of narrative medicine practice in China,we advise that medical professionals should integrate theories and treatments related to acupuncture,massage and positive psychology into their narrative medicine practice,taking into account the current state of clinical practice of acupuncturists and the importance of positive emotions in the field of psychology.This paper elucidates the value of combining acupuncture,massage,and positive psychology from the perspectives of mechanisms and clinical correlations,highlighting their impacts on patients'physical and mental health.To promote the integration of positive psychology with acupuncture and massage,it is proposed to refine the understanding of the efficacy of acupuncture points and develop theories on stimulating positive psychology in acupuncture and massage further more.

Network pharmacology and molecular docking analysis reveal insights into the molecular mechanism of Gualou Qumai Wan in clear cell renal cell carcinoma

Background:To initially clarify the potential therapeutic targets and pharmacological mechanism regarding Gualou Qumai Wan(GQW),a kind of traditional Chinese medicine(TCM),in clear cell renal cell carcinoma(ccRCC)by virtue of the network pharmacology analysis and molecular docking analysis.Methods:The screening of bioactive components and targets of GQW was based on the Traditional Chinese Medicine System Pharmacology(TCMSP)and the UniProt platform served for standardizing their targets.Online Mendelian Inheritance in Man(OMIM),PharmGkb,TTD,DrugBank and GeneCards databases were searched to collect the disease targets of ccRCC.Cytoscape assisted in constructing herb-compound-target(H-C-T)networks.The STRING database was searched for constructing the target protein-protein interaction(PPI)networks,while the R programming language served for analyzing GO functional terms and the KEGG pathways related to potential targets.Analyses of core genes related to survival and tumor microenvironment(TME)were conducted respectively based on the GEPIA2 database and TIMER 2.0 database.Human Protein Atlas(HPA)and The Cancer Genome Atlas(TCGA)helped to obtain core genes’protein expression as well as transcriptome expression level.Autodock Vina software validated the molecular docking regarding GQW components and pivotal targets.Results:The constructed H-C-T networks mainly had 33 compounds and 65 targets.A topological analysis of the PPI network identified that ESR1,AKT1,HIF1A,PTGS2,TP53 and VEGFA serve as core targets in the way GQW affects ccRCC.According to the GO and KEGG pathway enrichment analyses,the effects of GQW are mediated by genes related to hypoxia and oxidative stress as well as the Chemical carcinogenesis-receptor activation and PI3K-Akt signaling pathways.AKT1 shows a close relation to the recruitment of various immune cells and can remarkably affect disease prognosis according to reports.Molecular docking and molecular dynamics simulations showed that diosgenin has higher affinity with core targets.Conclusion:The study makes a comprehensive explanation of the biological activity,potential targets,as well as molecular mechanism regarding GQW against ccRCC,which promisingly assists in revealing the action mechanism of TCM formulae in disease treatment and the respective and scientific basis.

Pathogen profile and drug resistance analysis of spontaneous peritonitis in cirrhotic patients

AIM: To investigate the microbiological characteristics and drug resistance in liver cirrhosis patients with spontaneous peritonitis.METHODS: We analyzed the data of patients with liver cirrhosis and abdominal infection at the First Affiliated Hospital of Zhejiang University between January 2011 and December 2013. Pathogens present in the ascites were identified,and their sensitivity to various antibiotics was determined. RESULTS: We isolated 306 pathogenic bacteria from 288 cases: In 178 cases,the infection was caused by gram-negative strains(58.2%); in 85 cases,grampositive strains(27.8%); in 9 cases,fungi(2.9%); and in 16 cases,more than one pathogen. The main pathogens were Escherichia coli(E. coli)(24.2%),Klebsiella pneumoniae(18.9%),Enterococcus spp.(11.1%),and Staphylococcus aureus(7.5%). Of the 306 isolated pathogens,99 caused nosocomial infections and 207 caused community-acquired andother infections. The E. coli and K. pneumoniae strains produced more extended-spectrum β-lactamases in cases of nosocomial infections than non-nosocomial infections(62.5% vs 38%,P < 0.013; 36.8% vs 12.8%,P < 0.034,respectively). The sensitivity to individual antibiotics differed between nosocomial and non-nosocomial infections: Piperacillin/tazobactam was significantly more effective against non-nosocomial E. coli infections(4% vs 20.8%,P < 0.021). Nitrofurantoin had stronger antibacterial activity against Enterococcus species causing non-nosocomial infections(36.4% vs 86.3%,P < 0.009).CONCLUSION: The majority of pathogens that cause abdominal infection in patients with liver cirrhosis are gram-negative,and drug resistance is significantly higher in nosocomial infections than in non-nosocomial infections.

COVID-19 pandemic:Pathophysiology and manifestations from the gastrointestinal tract

The pandemic of coronavirus disease 2019(COVID-19),caused by a newly identifiedβ-coronavirus(SARS-CoV-2)has emerged as a dire health problem,causing a massive crisis for global health.Primary method of transmission was firstly thought to be animal to human transmission.However,it has been observed that the virus is transmitted from human to human via respiratory droplets.Interestingly,SARS-CoV-2 ribonucleic acid(RNA)has been isolated from patient stools,suggesting a possible gastrointestinal(GI)involvement.Most commonly reported clinical manifestations are fever,fatigue and dry cough.Interestingly,a small percentage of patients experience GI symptoms with the most common being anorexia,diarrhea,nausea and vomiting.The presence of viral RNA in stools is also common and fecal tests can be positive even after negative respiratory samples.The exact incidence of digestive symptoms is a matter of debate.The distribution of Angiotensin converting enzyme type 2 receptors in multiple organs in the body provides a possible explanation for the digestive symptoms’mechanism.Cases with solely GI symptoms have been reported in both adults and children.Viral RNA has also been detected in stool and blood samples,indicating the possibility of liver damage,which has been reported in COVID-19 patients.The presence of chronic liver disease appears to be a risk factor for severe complications and a poorer prognosis,however data from these cases is lacking.The aim of this review is firstly,to briefly update what is known about the origin and the transmission of SARS-CoV-2,but mainly to focus on the manifestations of the GI tract and their pathophysiological background,so that physicians on the one hand,not to underestimate or disregard digestive symptoms due to the small number of patients exhibiting exclusively this symptomatology and on the other,to have SARS-CoV-2 on their mind when the“gastroenteritis”type symptoms predominate.

Origin and genomic characteristics of SARS-CoV-2 and its interaction with angiotensin converting enzyme type 2 receptors, focusing on the gastrointestinal tract

The emergence of coronavirus disease-2019 induced by a newly identified bcoronavirus, namely severe acute respiratory syndrome coronavirus 2(SARSCoV-2) has constituted a public health emergency. Even though it was considered a zoonotic disease, the virus has also spread among humans via respiratory secretions. The expression and distribution of angiotensin converting enzyme type 2(ACE2) in various human organs might also show other possible infection routes. High ACE2 ribonucleic acid expression has been identified in the gastrointestinal tract(GI) indicating its importance as a possible infection pathway of SARS-CoV-2. ACE2 induces viral entry into the host and most importantly has been found to be associated with the function of the gut. Its deficiency has been implicated in several pathologies such as colorectal inflammation. The renin-angiotensin system(RAS) is an essential regulatory cascade operating both at a local tissue level and at the systemic or circulatory level. The RAS may be important in the pathogenesis of chronic liver disease and is associated with the up-regulation of ACE2. Thus, the aim of this review is firstly, the analysis of some important general and genome characteristics of SARS-CoV-2 and secondly, and most importantly, to focus on the utility of ACE2 receptors in both SARS-CoV-2 replication and pathogenesis, especially in the GI tract.

Primary localized malignant biphasic mesothelioma of the liver in a patient with asbestosis

We report a case of primary localized malignant biphasic mesothelioma of the liver in a 66-year-old man associated with asbestosis. The tumor was detected as a hepatic nodule, 4 cm in diameter, in the right lobe (S8 segment) on CT scan. Histopathological examination demonstrated an intrahepatic tumor with central necrosis consisting of a papillary epithelioid pattern on the surface of the liver, microcystic (microglandular or adenomatoid) pattern mainly in the subcapsular area and sarcomatoid pattern intermingled with microcystic pattern in the major part of the hepatic nodular tumor. Tumor cells, especially of epithelioid type, showed distinct immunoreactivity for mesothelial markers (WT-1, calretinin, D2-40, CK5/6, mesothelin, thrombomodulin) and no immunoreactivity for epithelial (adenocarcinoma) markers (CEA, CD15, BerEP4, BG8, MOC31). P53 immunoreactivity was detected focally in papillary epithelioid tumor cells and extensively in microcystic and sarcomatoid components, suggesting that the papillary epithelioid mesothelioma arose on the surface of the liver, and tumor cells showing microcystic and sarcomatoid patterns invaded and grew into the liver. To date, this is the first case of primary localized malignant biphasic mesothelioma of the liver, since all three primary hepatic mesotheliomas reported so far were epithelioid type.

Ulinastatin Exerts the Protective Effects of Lung by UpRegulating Aquaporins Expression in a Two-Hit Porcine Model of Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome(ARDS)is a syndrome characterized by significant lung edema,impaired permeability of lung microvascular endothelial cells with the mal-expression of aquaporins(AQPs).In this study,a two-hit porcine model of ARDS induced by smoking and methicillinresistant Staphylococcus aureus(MRSA)was developed,we investigate the AQPs expression and the influence of Ulinastatin(UTI)to them.Forty-nine healthy male domestic pigs aged 8–10 weeks and weighing 30±2 kg were used for the study.Anesthesia was maintained through continuous intravenous infusion of pentobarbital[8 mg/(kg∙h)].A 5-Fr PiCCO catheter(Pulsiocath PV2015L20;Pulsion Medical Systems,Munich,Germany)and a central venous catheter was inserted for hemodynamic monitoring,including mean arterial pressure(MAP),cardiac index(CI),systemic vascular resistance index(SVRI)and extravascular lung water index(ELWI).

Microencapsulation improves inhibitory effects of transplanted olfactory ensheathing cells on pain after sciatic nerve injury

Olfactory bulb tissue transplantation inhibits P2X2/3 receptor-mediated neuropathic pain. However, the olfactory bulb has a complex cellular composition, and the mechanism underlying the action of purified transplanted olfactory ensheathing cells（OECs） remains unclear. In the present study, we microencapsulated OECs in alginic acid, and transplanted free and microencapsulated OECs into the region surrounding the injured sciatic nerve in rat models of chronic constriction injury. We assessed mechanical nociception in the rat models 7 and 14 days after surgery by measuring paw withdrawal threshold, and examined P2X2/3 receptor expression in L4–5 dorsal root ganglia using immunohistochemistry. Rats that received free and microencapsulated OEC transplants showed greater withdrawal thresholds than untreated model rats, and weaker P2X2/3 receptor immunoreactivity in dorsal root ganglia. At 14 days, paw withdrawal threshold was much higher in the microencapsulated OEC-treated animals. Our results confirm that microencapsulated OEC transplantation suppresses P2X2/3 receptor expression in L4–5 dorsal root ganglia in rat models of neuropathic pain and reduces allodynia, and also suggest that transplantation of microencapsulated OECs is more effective than transplantation of free OECs for the treatment of neuropathic pain.

Anatomizing the “King of Neurosciences”

The human nucleus accumbens(NA), a major part of the ventral striatum, is the area of continuity between the putamen and head of the caudate nucleus. It consists of two parts, a shell laterally and a core medially. The first is mainly connected to the limbic system and the second to the extrapyramidal motor system. The NA, a major pleasure center of the human brain, acts as a limbic-motor interface and is involved in several cognitive, emotional and psychomotor functions. It has a modulating function in the amygdala-basal gangliaprefrontal cortex circuit. It is considered as the neural interface between motivation and action. Further, it is a principal modulator of the reward circuits and supplies motor expression to emotional responses. Such a clinical significance could easily explain the intense work taking place in the respective field of basic research. Its exceptional clinical importance justifies the title of the "King of Neurosciences" for this nucleus. Purpose of this editorial is to review the "informational paths" left behind by the few researchers who tried to explore the architecture(gross anatomy) of this ‘kingdom'. The first anatomical study focused on this nucleus came from Neto et al. The most extensive study of the NA gross, imaging, stereotactic and neurosurgical anatomy so far,came from the research efforts of Mavridis et al.

The relationship between body mass index, thickness of subcutaneous fat, and the gluteus muscle as the intramuscular injection site

An intramuscular injection (IMI) is an injection given directly into the central area of a specific muscle. Certain medicines need to be administered by the gluteal route for these to be effective. The aim of this study was to determine the influence of body mass index (BMI), subcutaneous fat, and muscular thickness of the dorsogluteal IMI site among healthy Japanese women. There were 39 healthy female subjects who volunteered and met the criteria. Their ages ranged from 40s to 60s (50.82 ± 6.04). With the data collected using the B-mode ultrasound images of the dorsogluteal site, it was found that the distance from the epidermis to the under-fascia (DEUF) of the gluteus maximus was dissimilar between the subject’s right and left buttocks. It was found that the distance from the epidermis to the iliac bone (DEI) was significantly more on the right than on the left buttocks. In the case of an adult Japanese woman with a BMI of 21 or more, the DEUF of the gluteus medius was found to be about 30 mm, and the DEI was approximately 50 mm or more. Based on these findings, it is recommended that a needle length of 38 mm (1.5 inches) can be safely used to administer IMIs to the gluteus medius muscle to effectively and efficiently deliver medications through the IMI route.

Hidden risks associated with conventional short intermittent hemodialysis:A call for action to mitigate cardiovascular risk and morbidity

The development of maintenance hemodialysis(HD)for end stage kidney disease patients is a success story that continues to save many lives.Nevertheless,intermittent renal replacement therapy is also a source of recurrent stress for patients.Conventional thrice weekly short HD is an imperfect treatment that only partially corrects uremic abnormalities,increases cardiovascular risk,and exacerbates disease burden.Altering cycles of fluid loading associated with cardiac stretching(interdialytic phase)and then fluid unloading(intradialytic phase)likely contribute to cardiac and vascular damage.This unphysiologic treatment profile combined with cyclic disturbances including osmotic and electrolytic shifts may contribute to morbidity in dialysis patients and augment the health burdenof treatment. As such, HD patients are exposed to multiple stressors including cardiocirculatory,inflammatory, biologic, hypoxemic, and nutritional. This cascade of events can be termed thedialysis stress storm and sickness syndrome. Mitigating cardiovascular risk and morbidityassociated with conventional intermittent HD appears to be a priority for improving patientexperience and reducing disease burden. In this in-depth review, we summarize the hidden effectsof intermittent HD therapy, and call for action to improve delivered HD and develop treatmentschedules that are better tolerated and associated with fewer adverse effects.

MTNR1B polymorphisms with CDKN2A and MGMT methylation status are associated with poor prognosis of colorectal cancer in Taiwan

BACKGROUND Identifying novel colorectal cancer(CRC)prognostic biomarkers is crucial to helping clinicians make appropriate therapy decisions.Melatonin plays a major role in managing the circadian rhythm and exerts oncostatic effects on different kinds of tumours.AIM To explore the relationship between MTNR1B single-nucleotide polymorphism(SNPs)combined with gene hypermethylation and CRC prognosis.METHODS A total of 94 CRC tumour tissues were investigated.Genotyping for the four MTNR1B SNPs(rs1387153,rs2166706,rs10830963,and rs1447352)was performed using multiplex polymerase chain reaction.The relationships between the MTNR1B SNPs and CRC 5-year overall survival(OS)was assessed by calculating hazard ratios with 95%CIs.RESULTS All SNPs(rs1387153,rs2166706,rs10830963,and rs1447352)were correlated with decreased 5-year OS.In stratified analysis,rs1387153,rs10830963,and rs1447352 risk genotype combined with CDKN2A and MGMT methylation status were associated with 5-year OS.A strong cumulative effect of the four polymorphisms on CRC prognosis was observed.Four haplotypes of MTNR1B SNPs were also associated with the 5-year OS.MTNR1B SNPs combined with CDKN2A and MGMT gene methylation status could be used to predict shorter CRC survival.CONCLUSION The novel genetic biomarkers combined with epigenetic biomarkers may be predictive tool for CRC prognosis and thus could be used to individualise treatment for patients with CRC.