Design and implementation of Internet of Things for emergency medical devices based on cloud-edge-device architecture / 生物医学工程学杂志

Internet of Things (IoT) technology plays an important role in smart healthcare. This paper discusses IoT solution for emergency medical devices in hospitals. Based on the cloud-edge-device architecture, different medical devices were connected; Streaming data were parsed, distributed, and computed at the edge nodes; Data were stored, analyzed and visualized in the cloud nodes. The IoT system has been working steadily for nearly 20 months since it run in the emergency department in January 2021. Through preliminary analysis with collected data, IoT performance testing and development of early warning model, the feasibility and reliability of the in-hospital emergency medical devices IoT was verified, which can collect data for a long time on a large scale and support the development and deployment of machine learning models. The paper ends with an outlook on medical device data exchange and wireless transmission in the IoT of emergency medical devices, the connection of emergency equipment inside and outside the hospital, and the next step of analyzing IoT data to develop emergency intelligent IoT applications.

Feasibility of individualized low radiation dose chest enhanced CT imaging: phantom and clinical study / 中华放射医学与防护杂志

Objective:To investigate the effect of the combination of Auto-prescription and ODM full on image quality and radiation dose of chest enhanced CT inorder to explore the feasibility of individualized low radiation dose chest enhanced CT. Methods:The phantoms PH-75 in two sizes were scanned with four scanning modes: group A, 120 kVp + Smart-mA; group B, 120 kVp + Smart-mA+ ODM full; group C, Auto-prescription + Smart-mA; group D, Auto-prescription + Smart-mA+ ODM full. The images of each group were reconstructed with 40%-80% ASIR-V (interval 20%), recorded as A 1-3-D 1-3. Image quality and radiation dose were evaluated in order to obtain optimal scanning modes. Totally 35 cases(from the First Hospital of Dalian Medical University during November 2021 to July 2022) of chest enhancement CT were collected prospectively in the clinical study using the parameters of D 2 group recorded as D patients. Patients in this group received chest enhancement CT scanning for the second time within three months. The CT parameters in first enhanced scanning recorded as A patient were as same as those in group A 1, and the parameters in second scanning recorded as D patient were as same as those in group D 2. The SNRs, CNRs, subjective grading and imaging findings of the lesion in two groups were compared. Results:In phantom study, the radiation dose of each group was statistically significant, and that in D group was the lowest. For two sizes of phantoms, A 1 was uesd as the control group in pairwise comparison. The SDs of B 1, C 1, and D 2 images had no statistical difference with that of A 1 ( P > 0.05), and SD of D 1was higher than that of A 1, and SDs of other groups were lower than that of A 1( F=10.77, 122.50, P<0.05). CNR of B 1 had no statistical difference with that of A 1, and the CNRs of other groups were higher( F=136.20, 30.21, P<0.05). Subjective scores of A 2, C 2, D 2 had no statistical difference with that of A 1 and those of other groups were lower than that of A 1( H=52.89, 43.95, P<0.05). In clinical study, 80 kVp was uesd for 22 cases and 100 kVp was used for 13 cases in D patients group. SNRs and CNRs in the D patients group were all higher than those in the A patients group ( P > 0.05). The consistency of image quality scores for two observers was good ( kappa = 0.754, P < 0.05). The median scores of the two groups were (4, 4). Conclusion:Auto-prescription combined with ODM full in chest enhanced CT imaging can achieve individualized low radiation dose with meeting the requirements of image quality and clinical diagnosis.

Early efficacy of three dimensional printed anatomical biomimetic cervical artificial disc replacement in the treatment of cervical degenerative diseases / 中华外科杂志

Objective: To investigate the efficacy and safety of a new cervical artificial disc prosthesis in the treatment of cervical degenerative diseases. Methods: The clinical data of 18 patients with single-level cervical degenerative diseases who underwent three dimensional printed anatomical bionic cervical disc replacement at Department of Spinal Surgery,Honghui Hospital,Xi'an Jiaotong University from May 2019 to July 2020 were analyzed retrospectively. There were 7 males and 11 females,aged (45±8) years old(range:28 to 58 years).The surgical segment was located at C3－4 level in 2 cases, C4－5 level in 5 cases, C5－6 level in 9 cases, and C6－7 level in 2 cases.The clinical and radiographic outcomes were recorded and compared at preoperative,postoperative times of one month and twelve months.The clinical assessments contained Japanese orthopedic association (JOA) score,neck disability index (NDI) and visual analogue scale (VAS).Imaging assessments included range of motion (ROM) of cervical spine, prosthesis subsidence and prosthesis anteroposterior migration.Repeated measurement variance analysis was used for comparison between groups,and paired t test was used for pairwise comparison. Results: All patients underwent the operation successfully and were followed up for more than 12 months.Compared with preoperative score,the JOA score,NDI and VAS were significantly improved after surgery (all P<0.01).There was no significant difference in postoperative ROM compared with 1-and 12-month preoperative ROM (t=1.570,P=0.135;t=1.744,P=0.099). The prosthesis subsidence was (0.29±0.13) mm (range: 0.18 to 0.50 mm) at 12-month postoperatively.The migration of prosthesis at 12-months postoperatively were (0.71±0.20) mm (range: 0.44 to 1.08 mm).There was no prosthesis subsidence or migration>2 mm at 12-month postoperatively. Conclusion: Three dimensional printed anatomical biomimetic cervical artificial disc replacement has a good early clinical effect in the treatment of cervical degenerative diseases, good mobility can be obtained while maintaining stability.

Preschool period neurodevelopmental follow-up in children underwent antergrade cerebral perfusion / 中华胸心血管外科杂志

Objective:To investigate the preschool period neurodevelopmental status and analyze the perioperative data which associated with delayed neurodevelopment in patients underwent antergrade cerebral perfusion(ACP).Methods:To access the preschool period neurodevelopmental status in patients underwent ACP using Griffiths mental development scale-Chinese(GDS-C). Patients were classified as normal development group(ND) and low development group(LD) depending on the outcomes of assessment. Perioperative data including age, weight, CPB time, aortic cross-clamp time, mean arterial pressure, ACP time and flow were analyzed retrospectively.Results:62 children who met the inclusion criteria, of which 19 were accessed by GDS-C scale. Fourteen cases were lagged in general quotient(GQ) compared with normal children. The outcomes of assessment in six subscales of GDS-C scale indicated that 13 cases were delayed in language(C) and practical reasoning(F). Eight cases were delayed in locomotor(A) and personal-social(B). Eleven cases were delayed in eye-hand coordination(D). Ten cases were delayed in performance(E). The children in LD group had significant longer CPB time and aortic cross-clamp time than those in ND group. There were no differences between two groups in other perioperative data.Conclusion:The incidence of preschool period neurodevelopmental delay after ACP in infants is relatively high. In detailed analysis, their language and practical reasoning ability are lagged significantly. In addition, the longer time of CPB and aortic cross-clamp are associated with the neurodevelopmental delay.

Machine Learning-Based Prediction of COVID-19 Severity and Progression to Critical Illness Using CT Imaging and Clinical Data

Objective@#To develop a machine learning (ML) pipeline based on radiomics to predict Coronavirus Disease 2019 (COVID-19) severity and the future deterioration to critical illness using CT and clinical variables. @*Materials and Methods@#Clinical data were collected from 981 patients from a multi-institutional international cohort with real-time polymerase chain reaction-confirmed COVID-19. Radiomics features were extracted from chest CT of the patients. The data of the cohort were randomly divided into training, validation, and test sets using a 7:1:2 ratio. A ML pipeline consisting of a model to predict severity and time-to-event model to predict progression to critical illness were trained on radiomics features and clinical variables. The receiver operating characteristic area under the curve (ROC-AUC), concordance index (C-index), and time-dependent ROC-AUC were calculated to determine model performance, which was compared with consensus CT severity scores obtained by visual interpretation by radiologists. @*Results@#Among 981 patients with confirmed COVID-19, 274 patients developed critical illness. Radiomics features and clinical variables resulted in the best performance for the prediction of disease severity with a highest test ROC-AUC of 0.76 compared with 0.70 (0.76 vs. 0.70, p = 0.023) for visual CT severity score and clinical variables. The progression prediction model achieved a test C-index of 0.868 when it was based on the combination of CT radiomics and clinical variables compared with 0.767 when based on CT radiomics features alone (p < 0.001), 0.847 when based on clinical variables alone (p = 0.110), and 0.860 when based on the combination of visual CT severity scores and clinical variables (p = 0.549). Furthermore, the model based on the combination of CT radiomics and clinical variables achieved time-dependent ROC-AUCs of 0.897, 0.933, and 0.927 for the prediction of progression risks at 3, 5 and 7 days, respectively. @*Conclusion@#CT radiomics features combined with clinical variables were predictive of COVID-19 severity and progression to critical illness with fairly high accuracy.

Advances on immune-related adverse events associated with immune checkpoint inhibitors / 医学前沿

Immunotherapy has recently led to a paradigm shift in cancer therapy, in which immune checkpoint inhibitors (ICIs) are the most successful agents approved for multiple advanced malignancies. However, given the nature of the non-specific activation of effector T cells, ICIs are remarkably associated with a substantial risk of immune-related adverse events (irAEs) in almost all organs or systems. Up to 90% of patients who received ICIs combination therapy experienced irAEs, of which majority were low-grade toxicity. Cytotoxic lymphocyte antigen-4 and programmed cell death protein-1/programmed cell death ligand 1 inhibitors usually display distinct features of irAEs. In this review, the mechanisms of action of ICIs and how they may cause irAEs are described. Some unsolved challenges, however really engrossing issues, such as the association between irAEs and cancer treatment response, tumor response to irAEs therapy, and ICIs in challenging populations, are comprehensively summarized.

Machine Learning-Based Prediction of COVID-19 Severity and Progression to Critical Illness Using CT Imaging and Clinical Data

Objective@#To develop a machine learning (ML) pipeline based on radiomics to predict Coronavirus Disease 2019 (COVID-19) severity and the future deterioration to critical illness using CT and clinical variables. @*Materials and Methods@#Clinical data were collected from 981 patients from a multi-institutional international cohort with real-time polymerase chain reaction-confirmed COVID-19. Radiomics features were extracted from chest CT of the patients. The data of the cohort were randomly divided into training, validation, and test sets using a 7:1:2 ratio. A ML pipeline consisting of a model to predict severity and time-to-event model to predict progression to critical illness were trained on radiomics features and clinical variables. The receiver operating characteristic area under the curve (ROC-AUC), concordance index (C-index), and time-dependent ROC-AUC were calculated to determine model performance, which was compared with consensus CT severity scores obtained by visual interpretation by radiologists. @*Results@#Among 981 patients with confirmed COVID-19, 274 patients developed critical illness. Radiomics features and clinical variables resulted in the best performance for the prediction of disease severity with a highest test ROC-AUC of 0.76 compared with 0.70 (0.76 vs. 0.70, p = 0.023) for visual CT severity score and clinical variables. The progression prediction model achieved a test C-index of 0.868 when it was based on the combination of CT radiomics and clinical variables compared with 0.767 when based on CT radiomics features alone (p < 0.001), 0.847 when based on clinical variables alone (p = 0.110), and 0.860 when based on the combination of visual CT severity scores and clinical variables (p = 0.549). Furthermore, the model based on the combination of CT radiomics and clinical variables achieved time-dependent ROC-AUCs of 0.897, 0.933, and 0.927 for the prediction of progression risks at 3, 5 and 7 days, respectively. @*Conclusion@#CT radiomics features combined with clinical variables were predictive of COVID-19 severity and progression to critical illness with fairly high accuracy.

Systemic lupus erythematosus: year in review 2019 / 中华医学杂志(英文版)

Systemic lupus erythematosus (SLE) is an autoimmune disease with extreme heterogeneity and potentially involvement of any organ or system. Numerous unanswered questions and challenges in SLE always prompt further exploration. In 2019, great progress in various aspects of SLE emerged. Both the classification criteria and management recommendation for SLE were updated. New promising medications have been widely developed and tested, although subsequent clinical studies are warranted. As an emerging number of most notable studies in SLE were published in both clinical area and basic research in 2019, we aim to summarize the highest quality data on SLE regarding novel insights of pathogenesis, updated recommendations, hot-spot issues on clinical manifestations, new understanding of disease prognosis, and most importantly, the therapeutic advances in SLE in this review.

Lymph node dissection along the left gastroepiploic vessels region in 4K laparoscopic radical gastrectomy with the surgeon on right position / 中华消化外科杂志

Minimally invasive surgery is widely adopted and recognized. In recent years new technologies of minimally invasive surgery emerge in endlessly. Application of 4K laparoscopy promotes the development, stangardization and training of minimally invasive surgery for gastrointestinal and colorectal diseases. Clear understanding of the anatomical structure of left gastroepiploic vessels is helpful for No.4 lymph node dissection. The surgeon′s accurate anatomy, good patience, and the high degree of coordination between surgeons and nurses help to reduce and prevent complications. The authors elaborates on lymph node dissection along the left gastroepiploic vessels region in 4K laparoscopic radical gastrectomy with the surgeon on right position

Infrapyloric lymph node dissection in 4K laparoscopic radical gastrectomy with the surgeon on right position / 中华消化外科杂志

Minimally invasive technique has been widely applied and recognized in gastrointestinal surgery. In recent years, technological innovation related to minimally invasive technology emerges in endlessly. The application of 4K ultra-high definition video display technology has played impartment roles in promoting the development of surgery, technical specifications and training of minimally invasive gastrointestinal surgery. Clearly understand the anatomical structure of the inferior pyloric region is an important theoretical basis for the dissection of No. 6 lymph node. Careful anatomy with good patience of the surgeons, and good cooperation between the surgeon and assistants are helpful to reduce and prevent complications. The authors investigate the infrapyloric lymph node dissection in 4K laparoscopic radical gastrectomy with the surgeon on right position.

Lymph node dissection along the left gastroepiploic vessels region in 4K laparoscopic radical gastrectomy with the surgeon on right position / 中华消化外科杂志

Minimally invasive surgery is widely adopted and recognized. In recent years new technologies of minimally invasive surgery emerge in endlessly. Application of 4K laparoscopy promotes the development, stangardization and training of minimally invasive surgery for gastrointestinal and colorectal diseases. Clear understanding of the anatomical structure of left gastroepiploic vessels is helpful for No.4 lymph node dissection. The surgeon′s accurate anatomy, good patience, and the high degree of coordination between surgeons and nurses help to reduce and prevent complications. The authors elaborates on lymph node dissection along the left gastroepiploic vessels region in 4K laparoscopic radical gastrectomy with the surgeon on right position

Infrapyloric lymph node dissection in 4K laparoscopic radical gastrectomy with the surgeon on right position / 中华消化外科杂志

Minimally invasive technique has been widely applied and recognized in gastrointestinal surgery. In recent years, technological innovation related to minimally invasive technology emerges in endlessly. The application of 4K ultra-high definition video display technology has played impartment roles in promoting the development of surgery, technical specifications and training of minimally invasive gastrointestinal surgery. Clearly understand the anatomical structure of the inferior pyloric region is an important theoretical basis for the dissection of No. 6 lymph node. Careful anatomy with good patience of the surgeons, and good cooperation between the surgeon and assistants are helpful to reduce and prevent complications. The authors investigate the infrapyloric lymph node dissection in 4K laparoscopic radical gastrectomy with the surgeon on right position.

Management of postoperative recurrence of inguinal hernia in adolescents: An analysis of 9 cases / 中国实用外科杂志

OBJECTIVE: To analyze the reoperation method and effect of recurrent inguinal hernia in adolescents after operation. METHODS: The data of 9 adolescent(13 to 18 years old) inguinal hernia patients with recurrence after surgical treatment admitted in the first people's hospital of Foshan from January 2006 to December 2018 were analyzed retrospectively. The methods of previous operation, reoperation, size of internal ring, major postoperative complications and recurrence rate were collected. RESULTS: Among the 170 adolescent patients who underwent inguinal hernia surgery,there were 9 cases of recurrent indirect inguinal hernia(the previous operation method was high ligation of the internal ring), including 2 cases of open surgery and 7 cases of laparoscopic surgery. Of the 9 patients, 3 had multiple recurrences and 6 had first recurrence. The sizes of internal ring were 0.3 to 3.0 cm in the operation. Surgical methods: 4 cases were performed with laparoscopic high ligation of internal ring, with the sizes of internal ring ranging from 0.3 cm to 2.0 cm. Laparoscopic inguinal hernia mesh repair was performed in 5 patients(3 patients with multiple recurrences)with the sizes of internal ring ranging from 1.5 cm to 3.0 cm. During the follow-up period of 6 months to 10 years, no wound or mesh infection, 3 patients showed discomfort in the inguinal area, 2 patients had mesh repair and 1 patient had high ligation. Seroma appeared in 1 patient which was repaired by mesh. One case of recurrence which was mesh repair.CONCLUSION: The choice of surgical method for recurrent inguinal hernia in adolescents should be based on the previous surgical method, recurrence frequency and the presence of large internal ring defect or transverse abdominal fascia defect. Laparoscopic high ligation is recommended for patients with primary recurrence of small internal ring defect. For patients with multiple recurrence or large internal ring defect, mesh repair is recommended.

Analysis of diseases distribution in Medical Information Mart for Intensive Care Ⅲ database / 中华危重病急救医学

Objective To study the distribution of diseases in Medical Information Mart for Intensive Care Ⅲ(MIMIC-Ⅲ) database in order to provide reference for clinicians and engineers who use MIMIC-Ⅲ database to solve clinical research problems. Methods The exploratory data analysis technologies were used to explore the distribution characteristics of diseases and emergencies of patients (excluding newborns) in MIMIC-Ⅲ database were explored; then, neonatal gestational age, weight, length of hospital stay in intensive care unit (ICU) were analyzed with the same method. Results In the MIMIC-Ⅲ database, 46 428 patients were admitted for the first time, and 49 214 ICU records were recorded. There were 26 076 males and 20 352 females; the median age was 60.5 (38.6, 75.6) years, and most patients were between 60 and 80 years old. The first diagnosis in the disease spectrum analysis was firstly ranked by circulatory diseases (32%), followed by injury and poisoning (14%), digestive system disease (8%), tumor (7%), respiratory disease (6%) and so on. Patients with ischemic heart disease accounted for the largest proportion of circulatory disease (42%), the proportion of these patients gradually increased with age of 60-70 years old, then decreased. However, the proportion of patients with cerebrovascular disease declined first and then increased with age, which was the main cause of death of circulatory system disease (ICU mortality was 22.5%). Injury and poisoning patients showed a significant decrease with age. Digestive system diseases were younger than the general population (most people aged between 50 to 60 years), and non-infectious enteritis and colitis were the main causes of death (ICU mortality was 18.3%). Respiratory infections were predominant in infected patients (34%), but circulatory system infections were the main cause of death (ICU mortality was 25.6%). Secondly, in the neonatal care unit, premature infants accounted for the vast majority (82%). As the gestational age increased, the duration of ICU was decreased, and the mortality was decreased. Conclusions The diseases distribution of patients can be provided by MIMIC-Ⅲ database, which helps to grasp the overview of the volume and age distribution of the target patients in advance, and carry out the next step of research. Meanwhile, it points out the important role of exploratory data analysis in electronic health records analysis.

Curative effect analysis on improved medial parapatellar approach in the treatment of posterior medial tibial plateau fracture / 局解手术学杂志

Objective To discuss the clinical effects of improved medial parapatellar approach in the treatment of posterior medial tibial plateau fracture( PMF-TP) . Methods 60 patients with PMF-TP were selected from June 2014 to June 2017 in our hospital;according to the surgical methods,all patients were divided into improved group (30 cases) and medial group (30 cases);the medial group was treated with routine medial approach, while the improved group was treated with improved medial parapatellar approach. The operation, complications, fracture reduction and knee joint function were compared between the two groups. The amount of bleeding,the incidence of complications and the operation,hospitalization,weight bearing exercise and fracture healing time of improved group were significantly lower than those in the after the operation, the knee flexion and extensional activity of improved group was significantly higher than that in the medial group,the difference was statistically significant(P<0. 05). The fracture re-duction and knee joint function excellent rate 6 months after operation of improved group were significantly higher than those in the medial group,the difference was statistically significant(P<0. 05). Results Compared with the posteromedial approach of the knee joint, the im-proved medial parapatellar approach features simple and safe operation. It is beneficial to early functional exercise, fracture reduction and re-habilitation of knee joint function.

Different observations of absorbable hemostatic membrane and hemostatic membrane in transforaminal lumbar interbody fusion / 实用医学杂志

Objective To investigate the effect of absorbable hemostatic membrane on hemostasis in lum-bar surgery.Methods From 2014 to 2015 in our department,40 patients(mainly for lumbar spinal stenosis and lumbar spondylolisthesis patients)were enrolled in lumbar surgery(via transforaminal interbody fusion,TLIF), and were rando mLy divided into the absorbable hemostatic membrane group and the ordinary hemostasis group. The volume of 24-hour incision drainage and the hemoglobin of preoperative and 1 day postoperation were compared between the two groups. Results Compared with the control group,the volume of incision drainage and hemoglobin in the absorbable hemostatic membrane group were significantly decreased at 24 hours after surgery. Conclusions The hemostatic effect of absorbable hemostatic membrane is very good in lumbar surgery,absorb-able hemostatic membrane is worthy of application in spinal surgery.

Preparation of Polydiallyl Dimethyl Ammonium Chloride Modified Reduced Graphene Oxide/Zinc Oxide Composite Materials and Its Application in Detection of Uric Acid / 分析化学

By using Zinc nitrate as precursor and hydraZine hydrate as reducing agent, polydiallyl dimethyl ammonium chloride modified reduced graphene oxide/Zinc oxide composite materials ( PDDA-rGO/ZnO) were prepared by simultaneous reduction of graphene oxide ( GO) and Zinc nitrate.The composite materials were characteriZed by Fourier transform infrared ( FTIR ) spectroscopy, X-ray diffractometer ( XRD ) and transmission electron microscopy ( TEM) , and their electrochemical catalytic activity for uric acid was studied by cyclic voltammetry ( CV ) and linear sweep voltammetry ( LSV ) measurements.The result showed that PDDA-rGO/ZnO modified glassy carbon electrode prepared here was sensitive, reproducible and stable, and had significant electrocatalytic activity for UA.When using linear sweep voltammetry for detection of UA, the responses of modified electrode were linear with UA concentration in the ranges of 0.02-0.1 mmol/L and 0.1-1.0 mmol/L respectively, with detection limit of 15.9 nmol/L (S/N=3).

Extracorporeal membrane oxygenation for failure to separate from bypass after arterial switch operation / 中华胸心血管外科杂志

Objective To summary the clinical experience of ECMO for failure to separate from bypass after arterial switch operation of TGA.Methods 8 TGA patients (6 boys and 2 girls,aged 1 day to 3.5 years and weighing 2.7-11.0 kg,3 VSD intact and 5 with VSD,others complicated malformation including COA,left ventricular outtract stenosis) were treated with VA ECMO owing to failure to separate from bypass caused by low output syndrome after ASO between July 2007 and June 2016.We collected the medical records and analyzed the indication,management and complication of ECMO for this patient population.There were two stages of ECMO supporting for low output after ASO,The first stage was to improve tissue perfusion and correct inner environment by high flow supporting,and the second stage was ventricular function training.ECMO was weaned when the blood pressure was more than 60 mmHg and the difference value of systolic pressure and diastolic pressure was 15-20 mmHg under medium dose inotropics supporting.Volume infusion was limited strictly during ECMO.Results The running time were 22-300 h.5 patients were weaned from ECMO successfully and 4 patients discharged to home.The long-term follow-up of echocardiography indicated normal cardiac function in 3 patients.1 older child had left cardiac failure again after weaning from ECMO 12 days later;he was supported by LVAD subsequently.LVAD was weaned after 236h supporting,unfortunately,He died from cardiac failure 50 days after LVAD weaning.3 patients could not wean from ECMO and died.The main complications were bleeding and pericardial tamponade.Conclusion VA ECMO was effective treatment for failure to separate from bypass after switch operation of TGA.The high mortality was seen in patients with intramural coronary arterial.The myocardial structure perhaps changed secondary in older TGA children,ECMO and LVAD can be used as short-term circulatory transition to artificial heart or transplant.Bleeding was the main complication of this population;surgical hemostasis and accurate coagulation management were the guarantee for successful ECMO running.

Targeted elimination of mutant mitochondrial DNA in MELAS-iPSCs by mitoTALENs

Mitochondrial diseases are maternally inherited heterogeneous disorders that are primarily caused by mitochondrial DNA (mtDNA) mutations. Depending on the ratio of mutant to wild-type mtDNA, known as heteroplasmy, mitochondrial defects can result in a wide spectrum of clinical manifestations. Mitochondria-targeted endonucleases provide an alternative avenue for treating mitochondrial disorders via targeted destruction of the mutant mtDNA and induction of heteroplasmic shifting. Here, we generated mitochondrial disease patient-specific induced pluripotent stem cells (MiPSCs) that harbored a high proportion of m.3243A>G mtDNA mutations and caused mitochondrial encephalomyopathy and stroke-like episodes (MELAS). We engineered mitochondrial-targeted transcription activator-like effector nucleases (mitoTALENs) and successfully eliminated the m.3243A>G mutation in MiPSCs. Off-target mutagenesis was not detected in the targeted MiPSC clones. Utilizing a dual fluorescence iPSC reporter cell line expressing a 3243G mutant mtDNA sequence in the nuclear genome, mitoTALENs displayed a significantly limited ability to target the nuclear genome compared with nuclear-localized TALENs. Moreover, genetically rescued MiPSCs displayed normal mitochondrial respiration and energy production. Moreover, neuronal progenitor cells differentiated from the rescued MiPSCs also demonstrated normal metabolic profiles. Furthermore, we successfully achieved reduction in the human m.3243A>G mtDNA mutation in porcine oocytes via injection of mitoTALEN mRNA. Our study shows the great potential for using mitoTALENs for specific targeting of mutant mtDNA both in iPSCs and mammalian oocytes, which not only provides a new avenue for studying mitochondrial biology and disease but also suggests a potential therapeutic approach for the treatment of mitochondrial disease, as well as the prevention of germline transmission of mutant mtDNA.

The relationship between the expression of bone sialoprotein and the bone metastasis in women with breast cancer / 安徽医科大学学报

Objective To investigate the relationship between the expression of bone sialoprotein(BSP) and the bone metastasis of breast cancer.Methods 840 cases of female breast cancer patients were retrospectively analyzed.The patients were divided into breast cancer bone metastasis group and no bone metastasis group according to whether the patients had bone metastasis after treatment,BSP expression in paraffin specimens of 840 cases of primary breastcancer was determined by immunohistochemical method,x2 test and COX survival analysis was used in analysis of influencing factors of bone metastasis and 5 years survival after treatment of breast cancer.Results 840 cases of breast cancer postoperatively of single factor analysis showed that age,primary tumor size,clinical stage,TNM and molecular typing were statistically significant(P ＜0.05).BSP in bonemetastasis group was significantly higher than that in patients without bone metastasis(non metastasis group and bone metastasis group)(P ＜ 0.05).However,CerbB-2,lymph node metastasis,whether menopause,pathological type,cell grading showed no correla tion.Multivariate analysis revealed that age,tumor volume,clinicalstage,three negative breast and high expression of BPS were risk factors for bone metastasis.COX survival analysis of breast cancer 5 year survival rate,BSP high expression group and low expression group was statistically significant (P ＜ 0.05).Conclusion The clinical stage,age,primary lesion size and molecular type are the main risk factors for bone metastasis after breast cancer treatment.Bone sialoprotein expression is closely related to breast cancer bone metastasis.