Introduction of Education Systems for Clinical Engineers in Japan

Japanese clinical engineer(CE) is a significant and unique profession compared with other nations with its dual clinical and technology focus and national licensing. The CE system of licensing was established in May 1987 under the Clinical Engineers Act. CEs are required to complete 3 to 4 years in designated schools and pass a national examination. It is a professional medical position responsible for the operation and maintenance of life-support and non-life-support medical device systems under the direction of physicians. Currently approximately 70 educational institutes- including technical colleges and universities- provide diverse and wide-ranging curricula from engineering to various clinical disciplines to produce CEs. Since clinical practice training is mandatory as a part of institute work, an important approach for CEs is gained by working in hospitals. The comprehensive curricula and the licensing system in Japan together serve to keep the appropriate quantity and quality of CEs. The Japan Association for Clinical Engineers(JACE) was established in February 1990; one of its aims is to support improvement of CEs throughout their careers through various lectures, seminars, on-the-job trainings, workshops, and an annual member meeting. New CEs can now take advantage of video e-learning. For junior CEs, there are seminars for hyperbaric oxygen therapy, blood purification, heart-lung bypass, respiratory therapy, operating room, intensive care unit, arrhythmia and aphaeresis related devices, as well as healthcare technology management(HTM). Also, the institutes provide a leadership seminar alongside this clinical practice training. Besides the licensing process, a proper certification system for CEs is a critical element in the clinical field. This enhances the ability of CEs to engage in more extensive duties and develop specialties, as well as to provide better healthcare. Associated societies provide certification with technology qualifications in dialysis, extracorporeal circulation, respiratory therapy, clinical medical devices, hyperbaric oxygen therapy, and aphaeresis treatment. JACE also launched a unique certification system in 2010, with specializations in blood purification, arrhythmia, respiratory, and hyperbaric oxygen care. What is the difference between certification by the associated societies and that offered by JACE? Certification by the associated societies provides basic knowledge to pass specialty examinations. Certifications by JACE promote deeper knowledge to enhance clinical decisionmaking and to encourage wider experience. JACE also continues to investigate other certifications. In summary, Japan has introduced a national licensing system for keeping an intake of constant quality and quantity of CEs. Additionally, ongoing workshops and seminars stimulate in-depth knowledge and a higher level of medical care for patients. Together, a system of lifelong education for CEs has been built.

Clinical Engineering Benchmarking Comparison Between Zhejiang Province and American Hospitals

Clinical engineering(CE) has evolved rapidly over the last 25 years in China. Among the 34 provincial-level administrative units within China, the Zhejiang Province is one of the most advanced in terms of healthcare technology maintenance and management. In order to determine Zhejiang's current stage of development and opportunities for further improvement, a comparison of the performance of its CE departments was made against hospitals in the USA. Data were collected from 21 Zhejiang hospitals and compared to those from 270 acute-care hospitals in USA collected by Truven Health Analytics. The benchmarking comparison was made in three categories: operational, financial, and productivity. Within the operational category, the following metrics were compared: equipment inventory size/operating beds, annual repairs/inventory size, and annual scheduled maintenance/inventory size. Within the Financial category, the following metrics were compared: total CE expense/operating beds and total CE expense/total hospital expense. Within the Productivity category, the following metrics were compared: total CE full-time equivalent(FTE)/inventory size and total CE FTE/total hospital expense. These comparisons showed that:(1) While the equipment inventory in Zhejiang tends to be much smaller than USA for hospitals of comparable amount of operating beds, the numbers of repairs and scheduled maintenance per inventory size are similar;(2) The total CE expense/total hospital expense ratio is around 1% in both Zhejiang and USA; however, the total CE expense/operating beds and total CE expense/cost of equipment inventory are significantly lower in Zhejiang than USA;(3) The FTE amount in Zhejiang is significantly higher than in USA relative to both inventory size and total hospital operating expense, but significantly lower relative to the number of operating beds. The fact that repairs and scheduled maintenance are similar in Zhejiang and USA shows that CE leaders are managing equipment in comparable manner. Most of the differences found in the comparisons were traced to a few factors. First, the average length of stay in China is substantially higher than USA, which explains why hospitals in Zhejiang tend to have more operating beds but fewer pieces of equipment. Second, labor cost is significantly lower in China than USA, thus allowing Zhejiang hospitals to employ more workers than their American counterparts. Third, there is significantly difference in the cost of living between China and USA; Finally, being public entities Chinese hospitals are managed and operated in a different manner than American hospitals, which are mostly private, albeit nonprofit organizations. Nonetheless, it is interesting to note that hospitals in both areas spend roughly 1% of their total expenditure for CE. The results suggest that CE in Zhejiang is comparable to USA in terms of managerial excellence but there could be some room for improvement in financial management and productivity.

Heart and skeletal muscle insulin resistance but not myocardial blood flow reserve could be related to chronic use of thiazolidione in patients with type-2 diabetes

Heart and skeletal muscle insulin resistance and abnormal myocardial flow reserve (MFR) occurs in patients with type-II diabetes. Improvement of heart and skeletal muscle insulin resistance with rosiglitazone use over 16 weeks have been reported. However, it is not clear whether chronic use of troglitazone can improve heart and skeletal muscle insulin resistance and MFR. Materials and Methods: To test the hypothesis whether effects of troglitazone on heart and skeletal muscle insulin resistance and MFR in patients with type-II diabetes, rest and dipyridamole stress perfusion positron emission tomography (PET) with 13N-ammonia and heart and skeletal muscle 18FDG PET scans under insulin clamping were undertaken before and 12 month after the initiation of troglitazone therapy (400 mg/day) in 23 patients with type-II diabetes. Twenty patients with type-II diabetes without CAD and without medications were served as controls. In controls, any medications were not added from the first PET study and 12 months after the second PET study. Results: Baseline myocardial blood flow (MBF) was comparable before and after the troglitazone group as was the controls. MBF during dipyridamole administration (0.56 mg/min/kg) was not significantly improved in troglitazone group and controls. MFR was not improved in troglitazone group and controls. In troglitazone group, whole body glucose disposal rate (GDR;μmole/min/kg) significantly improved (pre;19.0 ± 9.55, post;28.7 ± 15.3, p as did the skeletal muscle glucose utilization rate (SMGU (μmole/min/kg);pre;20.3 ± 12.0, post;34.8 ± 10.6, p insulin resistance is implicated in patients with type-II diabetes and impaired MFR is uncoupled with insulin resistance in the whole body and heart and skeletal muscle in patients with type-II diabetes.

Evaluation of the Pharmacokinetics of Nafamostat Mesylate during Continuous Renal Replacement Therapy

Continuous renal replacement therapy (CRRT) is the preferred dialysis modality in critical care settings for patients with hemodynamic instability. Nafamostat mesylate (NM) is an anticoagulant commonly used (mainly in Japan) during CRRT in patients with high bleeding risk. In this study, we evaluated the pharmacokinetics of NM during CRRT. Patients undergoing CRRT therapy and using NM as the anticoagulant in the intensive care unit were enrolled in the study. Blood was collected from the CRRT circuit just after blood removal, just before and after the membrane for CRRT, and from the filtrates after the membrane. NM concentrations were measured using high-performance liquid chromatography. NM was detected in the intracorporeal circulation during CRRT in some cases, and liver enzymes were severely elevated in almost all of the cases. Coagulation time was prolonged even before the initiation of NM administration in these cases and may be associated with liver damage. This study suggests that NM dosage should take into account liver damage assessed by elevated liver enzymes.

Appropriate Heart Rate in a Patient with Repaired Tetralogy of Fallot

Appropriate heart rate in a failing pulmonary ventricle remains unknown, particularly in congenital heart diseasewith unique hemodynamics. A 71-year-old male with repaired tetralogy of Fallot and a pacemaker for a sinusnode dysfunction suffered from heart failure symptoms with preserved left ventricular function. Simply changingthe pacemaker’s lower rate from 60 to 75 bpm, New York Heart Association classification improved from III to II,and hemodynamic parameters drastically improved. We regarded this case as informative. Appropriate heart ratecould be higher in congenital patients with failing right and non-failing left ventricles than in adults with malfunctioningLV.

Functional imaging of skeletal muscle glucose metabolism by ¹⁸FDG PET to characterize insulin resistance in patients at high risk for coronary artery disease

Insulin resistance is associated with several coronary risk factors and is thought to play a critical role for the development of coronary artery disease. Insulin resistance has several causes, including an impaired skeletal muscle glucose utilization rate (SMGU), reduced peripheral blood flow, and altered fatty tissue metabolism, with SMGU being considered the most important. Nonetheless, insulin resistance has only been estimated by the glucose disposal rate (GDR) in previous studies. Methods: Skeletal muscle metabolic imaging with 18FDG and positron emission tomography (PET) was undertaken to measure SMGU during hyperinsulinemiceuglycemic clamping in 22 normotensive type-2 diabetics under no medications (T2- DM), 17 normotensive non-diabetic hypertriglyceridemics, 22 patients with hypertension, and 12 agematched controls. Whole body insulin resistance was assessed by the GDR during hyperinsulinemiceuglycemic insulin clamping. Results: The SMGU and GDR were significantly reduced in T2DM (32.1 ± 16.6 μmol/min/kg and 24.3 ± 13.0 μmol/min/kg, respectively), hypertriglyceridemics (36.5 ± 13.5 μmol/min/ kg and 22.7 ± 8.07 μmol/min/kg respectively) and patients with hypertension (35.4 ± 26.6 μmol/min/kg and 29.0 ± 9.90 μmol/min/kg, respectively) compared with controls (72.2 ± 44.1 μmol/min/kg and 43.0 ± 22.9 μmol/min/kg, p < 0.01, respectively). In all groups studied, SMGU was significantly correlated with GDR (r = 0.76, p < 0.01) and GDR (F = 13.9) was independently related to SMGU (r = 0.81, p < 0.01). Conclusion: Insulin resistance is significantly associated with SMGU to a similar degree among patients with T2DM, essential hypertension and hypertriglyceridemia. 18FDG PET functional imaging allows insulin resistance to be assessed.

Measurement of lumbar muscle glucose utilization rate can be as useful in estimating skeletal muscle insulin resistance as that of thigh muscle

Background: Skeletal muscle glucose utilization (SMGU) can be accessed by positron emission tomography (PET) and18F-FDG to characterize insulin resistance. The quantity of skeletal muscle in the lumbar is sufficient to indicate that SMGU in the lumbar (SMGU- lumbar) can be measured with18F-FDG PET of the chest instead of obtaining thigh muscle SMGU (SMGU-thigh). This would reduce PET scan time to avoid thigh muscle PET scan. This study was aimed to compare SMGU-lumbar and thigh muscle SMGU under insulin clamping to identify the validity of measurements of SMGU in the lumbar for studies of insulin resistance. Methods: Thirty-three patients underwent sequential dynamic18F-FDG PET of both the thoracic (37 min) and thigh region (22 min) during hyperinsulinemic euglycemic insulin clamping. Both SMGU-lumbar and SMGU-thigh were calculated by Patlak graphical analysis. Whole body insulin resistance was assessed by a whole body glucose disposal rate during hyperinsulinemic euglycemic insulin clamping. Input function was obtained from the time activity curve of the descending aorta and venous blood sampling as previously validated. Results: SMGU-thigh (0.0506 ± 0.0334 μmol/min/g) was comparable to SMGU-lumbar (0.0497 ± 0.0255 μmol/min/g). The Bland-Altman method of difference plot analysis showed a significant correlationship between SMGU- thigh and SMGU-lumbar (r = 0.506, p = 0.0028). There were seen very good significant correlationship between whole body glucose utilization rate in both thigh (r = 0.737, p = 0.0001) and lumbar (r = 0.772, p = 0.0001). Conclusion: These results support the validity of measuring SMGU-lumbar to estimate insulin resistance during PET imaging of the chest.

Molecular adsorbent recirculating system therapy in a rare case of fulminant hepatitis

Background: Acute hepatitis C virus infection leading to fulminant hepatitis is very rare whereas Hepatitis C virus (HCV) infection is one of the main causes of chronic liver disease worldwide. The repertoire of substances that accumulate in the blood in fulminant hepatic failure cause neurological abnormalities, aggravate injury to the liver and other organs, suppress the ability of residual hepatocytes to perform organ-specific functions (sick cell syndrome), and inhibit the hepatic regenerative response especially in fulminant hepatitis Virus C which has subacute clinical evolution and takes time to manifest. Liver support technology is evolving as different techniques become available that assist the remaining functional cell mass by providing specific liver functions. Case Presentation: We report a case of Fulminant C virus Hepatitis, successfully treated with albumin dialysis Molecular Adsorbent Recirculating System (MARS). At time of admittance the patient presented: Model End-stage Liver Disease (MELD)-36;Child Turcotte Pugh (CTP)-C(13);Sequential Organ Failure Assestment (SOFA)-12, Glasgow Coma Score (GCS)-11. The patient underwent six sessions of MARS in Intensive Care Unit (ICU) in association with standard medical therapy (SMT). The patient survived and was discharged from the hospital in good condition after 40 days without liver transplantation (LT).

Predicting and Suppressing Oversensing of a Pacemaker in Plain X-Ray Photography

We conducted experiments of oversensing generation of pacemaker (PM) and X-irradiation direction dependency of PM, and examined the oversensing suppression method, using 8 different types of PMs. It was found out from this experiment that oversensing would occur when some conditions (X-irradiation direction, X-irradiation intensity) are met. Oversensing occurred with the most low irradiation conditions (kV × mA) when PM was irradiated at 90° (vertically to C-MOS;Complementary Metal Oxide Semiconductor). The acuter the angle of irradiation is (α > 90° < α), the higher the irradiation conditions (kV × mA) at which oversensing start to occur. In plain X-ray photography, oversensing was confirmed under the irradiation conditions of (cervical spine, thoracic spine, lateral thoracic spine, rib, shoulder joint, collarbone, humerus, and chest).Once the irradiation angle and irradiation conditions (kV × mA) are available, oversensing is predictable to some extent. Our findings will help to predict oversensing generation of plain X-ray photography and suppress oversensing. Oversensing can be suppressed in most of the radiography by lowering tube current to 100 mA, but a 1.0 mm High-Density Tungsten Sheet must be put on PM in high tube voltage radiography.

Selection of Hammering Sound Collection Devices for the Development of Total Hip Arthroplasty Support Systems

In total hip arthroplasty, intraoperative femoral fractures can be avoided by analyzing the hammering sounds from the stem inserted into the femur. This procedure is based on a hammering test that makes use of the fact that sound depends on the stability of the object. This technique is generally used in engineering. A system designed to avoid excessive stem hammering by predicting the intraoperative fracture risk based on this technique and software for real-time spectra analysis has been developed with repetitive improvements. The remaining technical challenge lies in selecting an appropriate sound collection device and building a compact and easy unit for use. This study reviewed the types of directional microphones suitable for the sound collection system to develop a practical THA support system. Four types of microphones based on selected methods were used to collect and compare the peak frequencies of the hammering sounds and make comparisons between them, and the built system was used to conduct clinical trials. For miniaturization and operational ease of the unit, plug-in unidirectional microphones are appropriate. However, no laboratory-level data has been collected, and thus, further data accumulation is necessary.

A cascade model of information processing and encoding for retinal prosthesis

Retinal prosthesis offers a potential treatment for individuals suffering from photoreceptor degeneration diseases.Establishing biological retinal models and simulating how the biological retina convert incoming light signal into spike trains that can be properly decoded by the brain is a key issue.Some retinal models have been presented,ranking from structural models inspired by the layered architecture to functional models originated from a set of specific physiological phenomena.However,Most of these focus on stimulus image compression,edge detection and reconstruction,but do not generate spike trains corresponding to visual image.In this study,based on stateof-the-art retinal physiological mechanism,including effective visual information extraction,static nonlinear rectification of biological systems and neurons Poisson coding,a cascade model of the retina including the out plexiform layer for information processing and the inner plexiform layer for information encoding was brought forward,which integrates both anatomic connections and functional computations of retina.Using MATLAB software,spike trains corresponding to stimulus image were numerically computed by four steps：linear spatiotemporal filtering,static nonlinear rectification,radial sampling and then Poisson spike generation.The simulated results suggested that such a cascade model could recreate visual information processing and encoding functionalities of the retina,which is helpful in developing artificial retina for the retinally blind.

Inhibition of the Oversensing of Cardiac Pacemakers in Chest CT

Objectives: The purpose of this study is to identify how to manage oversensing of pacemakers in chest CT. Methods: Four different models of pacemakers were examined to select the pacemaker generating oversensing. To the pacemaker with oversensing, intermittent switching X-ray was exposed using ECG-gated CT helical scan system at prospective CTA mode. IVY Model was used to synchronize the ECG. Only during in the alert period that is non-refractory and sensing is available, intermittent switching X-ray (300 msec/sec) was exposed in chest CT. For comparison, the same intermittent switching X-ray (300 msec/sec) was exposed in the refractory period when sensing was not available. Results: Oversensing was detected only in one of the four pacemakers tested. In this pacemaker, oversensing was generated by exposure of the intermittent switching X-ray in the alert (non-refractory) period, but oversensing was not observed in the refractory period. Conclusion: A pacemaker has alert and refractory periods. Oversensing of a pacemaker was found to be inhibited by selective ECG-synchronized exposure in the refractory period. Since all pacemakers have the refractory period, the results of this study can be widely applied to the patients with pacemakers in chest CT, and their chest CT can be operated safely.

Investigation of Inspiratory Circuit Condensation due to Room Temperature in a Heated Humidifier during Mechanical Ventilation

Heating and humidification control during mechanical ventilation is important. Water condensation can occur due to insufficient humidification. Condensation in the breathing circuit can cause various adverse events. In this study, we investigated whether the occurrence of tubing condensation in the breathing circuit could be affected by room temperature using a simulated respiratory circuit with a humidifier. The room temperature was set at 23°C, 25°C, and 27°C, and mechanical ventilation was performed for 8 h. The inspired gas was appropriately heated and humidified according to the manufacturer’s instructions. The weight of the circuit was measured every 2 h at room temperature to estimate the amount of condensation. During the mechanical ventilation, condensation continued to increase at a room temperature of 23°C, but only for the first 2 h at 25°C, and did not occur at 27°C. The room temperature of the indoor environment was one of the factors generating water condensation in the breathing circuit with a humidifier even when a heater wire in the breathing circuit was appropriately operated.

Heart-on-chips screening based on photonic crystals

Recently,organ-on-chips have become a fast-growing research field with the widespread development of microfluidic chips and synthetic materials in tissue engineering.Due to the existing cardiotoxicity of many cardiovascular drugs,heart-onchips which are promising to replace traditional animal models have been extensively researched and developed to mimic human organ functions in vitro.The heart-on-chips mainly focus on cardiac mechanics,which is regarded as the central indicator of in vitro heart models and drug testing.Traditional methods for the detection of myocardial mechanics have been demonstrated complex and inefficient in heart-on-chips.Therefore,photonic crystal materials with unique optical properties have attracted interests and have been introduced into the heart-on-chips,developing a visualized self-reporting system for cardiomyocytes activity monitoring.In this review,photonic crystal-based heart-on-chips for biosensing are introduced,as well as the fabricationmethods and design criteria of them.The characterizations of the photonic crystal materials are classified into optical properties and structural properties,and their applications in cell culture and biosensing are further discussed.Then,several representative examples and developments of the integration of photonic crystal materials into microfluidic chips are described in detail.Finally,potentials and limitations are put forward to promote the development of the photonic crystal-based intelligent heart-on-chips.

A New Approach: Chronotherapy in Acute Blood Purification for Septic Shock

Circadian rhythms are daily oscillations of multiple biological processes. Recently, relationships between circadian rhythms and immune functions have also been described. In a mouse sepsis model, the death rate due to lipopolysaccharide (LPS)-induced endotoxic shock was found to be dependent on LPS administration as determined by circadian time. In humans, a pronounced inflammatory response to endotoxemia differs depending on whether it is daytime or night-time: Levels of tumor necrosis factor-alpha and interleukin-6 were higher during the night. Therefore, it is reasonable to assume that circadian rhythms influence not only organ dysfunction and the prognosis induced by LPS, but also the therapeutic effect of anti-LPS therapy such as Polymyxin-B direct hemoperfusion. We herein postulate the concept that it is important to discuss septic shock treatment in terms of whether or not the treatment is adjusted for the optimal time window as determined by circadian rhythms.

Assessing Donor Liver Quality and Restoring Graft Function in the Era of Extended Criteria Donors

Liver transplantation(LT)is the final treatment option for patients with end-stage liver disease.The increasing donor shortage results in the wide usage of grafts from extended criteria donors across the world.Using such grafts is associated with the elevated incidences of post-transplant complications including initial nonfunction and ischemic biliary tract diseases,which significantly reduce recipient survival.Although several clinical factors have been demonstrated to impact donor liver quality,accurate,comprehensive,and effective assessment systems to guide decision-making for organ usage,restoration or discard are lacking.In addition,the development of biochemical technologies and bioinformatic analysis in recent years helps us better understand graft injury during the perioperative period and find potential ways to restore graft function.Moreover,such advances reveal the molecular profiles of grafts or perfusate that are susceptible to poor graft function and provide insight into finding novel biomarkers for graft quality assessment.Focusing on donors and grafts,we updated potential biomarkers in donor blood,liver tissue,or perfusates that predict graft quality following LT,and summarized strategies for restoring graft function in the era of extended criteria donors.In this review,we also discuss the advantages and drawbacks of these potential biomarkers and offer suggestions for future research.

Skeletal muscle and whole body insulin resistance but not cardiac muscle insulin resistance could be improved by troglitazone therapy within 12 weeks in type-2 diabetes

Background: Existence of myocardial insulin resistance (IR) has been reported in type II diabetics (T2- DM) and coronary artery disease (CAD). Improvement in heart and skeletal muscle IR after thiazolidinedione’s therapy was reported in T2DM and CAD. However effects of troglitazone therapy (TRO) on myocardial IR remain uncertain. To clarify heart and skeletal muscle and whole body IR in T2DM without CAD by TRO to clarify whether TRO would provide different results. Methods: We analyzed data on 15 T2DM patients who underwent dynamic PET with 18F-FDG under insulin clamping before and during TRO (200 mg/day) and 17 controls. Results: Whole body glucose disposal rate (WBGR mg/min/kg) in T2DM before TRO (3.41 ± 1.72) was significantly lower than in controls (9.76 ± 2.97, p < 0.01) as was the skeletal muscle glucose utilization rate (SMGU mg/min/kg);T2DM (0.367 ± 0.217) vs. controls (1.34 ± 0.613, p < 0.01) and myocardial glucose utilization rate (MGU mg/min/kg;T2DM 5.86 ± 2.03 vs. controls 7.34 ± 1.80, p < 0.05). WBGR in T2DM during TRO (5.17 ± 2.75, p < 0.05) was significantly higher than that before TRO, as was the SMGU (0.782 ± 0.20, p < 0.05). The MGU in T2DM during TRO (6.59 ± 0.72) was comparable with that before TRO. Conclusion: Myocardial IR response to TRO differed from that in skeletal muscle and the whole body in T2DM without CAD.

Polymixin-B hemoperfusion in a case intolerant to conventional antibiotic therapy

In this study we document how it was possible to resolve the septic complications of abdominal surgery, subjecting a patient severely allergic to intravenous antibiotics. We performed the hemoperfusion with polymyxin-B columns (PMX-DHP), guiding the therapy by assaying endotoxin activity and evaluating the clinical status of the patient after each session of PMX-DHP. The stabilization of hemodynamic and inflammatory frameworks were immediately observed after the PMX-DHP. The patient could be safely discharged five days after the discontinuation of the therapy. Our findings confirms data already published in literature concerning the effectiveness of PMX-DHP.

Value of negatively correlated miR-205-5p/HMGB3 and miR-96-5p/FOXO1 on the diagnosis of breast cancer and benign breast diseases

Background:MicroRNA(miRNA)and mRNA levels in matching specimens were used to identify miRNA–mRNA interactions.We aimed to integrate transcriptome,immunophenotype,methylation,mutation,and survival data analyses to examine the profiles of miRNAs and target mRNAs and their associations with breast cancer(BC)diagnosis.Methods:Based on the Gene Expression Omnibus(GEO)database and The Cancer Genome Atlas(TCGA),differentially expressed miRNAs and targeted mRNAs were screened from experimentally verified miRNA-target interaction databases using Pearson's correlation analysis.We used real-time quantitative reverse transcription polymerase chain reaction to verify BC and benign disease samples,and logistic regression analysis was used to establish a diagnostic model based on miRNAs and target mRNAs.Receiver operating characteristic curve analysis was performed to test the ability to recognize the miRNA-mRNA pairs.Next,we investigated the complex interactions between miRNA-mRNA regulatory pairs and phenotypic hallmarks.Results:We identified 27 and 359 dysregulated miRNAs and mRNAs,respectively,based on the GEO and TCGA databases.Using Pearson's correlation analysis,10 negative miRNA-mRNA regulatory pairs were identified after screening both databases,and the related miRNA and target mRNA levels were assessed in 40 BC tissues and 40 benign breast disease tissues.Two key regulatory pairs(miR-205-5p/High mobility group box 3(HMGB3)and miR-96-5p/Forkhead Box O1(FOXO1))were selected to establish the diagnostic model.They also had utility in survival and clinical analyses.Conclusions:A diagnostic model including two miRNAs and their respective target mRNAs was established to distinguish between BC and benign breast diseases.These markers play essential roles in BC pathogenesis.

Identification of a serum three-microRNA signature for cervical cancer diagnosis

To the Editor:Cervical cancer(CC)is one of the leading causes of cancer deaths in women around the world.[1]In clinical practice,screening methods such as human papillomavirus testing and cytology-based detection have the disadvantages of having a high false rate,being hysteretic or ineffective.[2]Novel non-invasive biomarkers that can help diagnose CC with higher specificity and sensitivity are in great demand.MicroRNA(miRNA)is a type of non-coding small RNA of 18 to 25 nucleotides in length.Circulating miRNAs show the great potential of being cancer biomarkers for the stable existence in peripheral serum or plasma.[3]In this study,we performed a four-stage experiment using a total of 108 CC and 108 normal control(NC)serum samples to explore the diagnostic potential of serum miRNAs in CC.The schematic diagram of the experimental procedure was shown in Supplementary Figure 1,http://links.lww.com/CM9/A429.