[Research of miR-29a on TGF-ß1/Smad3 pathway in pulmonary fibrosis induced by neodymium oxide].

Objective: To exploring the regulatory effect of miR-29a on the transforming growth factor-ß1 (TGF-ß1) /Smad homolog 3 (Smad3) pathway during the process of rare earth neodymium oxide (Nd(2)O(3)) induced pulmonary fibrosis in mice. Methods: In March 2021, 72 SPF grade C57/BL6J male mice were selected and randomly divided into a control group, Nd(2)O(3) group, Nd(2)O(3)+miR-29a agomir group, and Nd(2)O(3)+NC agomir group, with 18 mice in each group. The Nd(2)O(3) group, Nd(2)O(3)+miR-29a agomir group, and Nd(2)O(3)+NC agomir group were treated with non exposed tracheal instillation, with a dust concentration of 250 mg/ml and a dust volume of 0.1 ml. The control group was given the same volume of physiological saline. After exposure to Nd(2)O(3), 0.1 ml (5 nmol) of miR-29a agomir was injected into the tail vein of mice in the Nd(2)O(3)+miR-29a agomir group every 3 days, while 0.1 ml of NC agomir was injected into the tail vein of mice in the Nd(2)O(3)+NC agomir group. On the 7 th, 14 th, and 28 th days after dust exposure, 6 mice were killed in each group, and the lung tissue of the mice was taken out. HE staining was used to observe the pathological status of the mouse lung tissue; ELISA method was used to detect the levels of TGF-ß1 and connective tissue growth factor (CTGF) in lung tissue; Use qRT-PCR detection method to detect the expression level of TGF-ß1 mRNA; Using immunofluorescence assay to detect the expression level of Smad3 in mouse lung tissue; Use bioinformatics websites such as TargetScan7 and miRDB to predict the target gene of miR-29a. When the metrological date were satisfied with normal distribution, Mean±SD was used for comparison between groups, t test was used for two indepent samples, and LSD method was used when the variance was homogeneity in pairwise comparison. Results: HE staining showed that the Nd(2)O(3) group of mice showed obvious infiltration of inflammatory cells and structural disorder of alveoli in the early stage of lung tissue. At 28 days, the collagen fibers in the mouse lung tissue increased and the lung tissue showed fibrotic honeycomb like changes. The degree of pulmonary fibrosis in the Nd(2)O(3)+miR-29a agomir group of mice was significantly reduced; The content of TGF-ß1 and CTGF in the lung tissue of mice in the Nd(2)O(3)+miR-29a agomir group was lower than that in the Nd(2)O(3)+NC agomir group (P<0.05) ; The relative expression level of TGF-ß1 in the lung tissue of mice in the Nd(2)O(3)+miR-29a agomir group was lower than that in the Nd(2)O(3)+NC agomir group (P<0.05) ; The expression level of Smad3 in the nucleus of the Nd(2)O(3)+miR-29a agomir group was lower than that of the Nd(2)O(3)+NC agomir group (P<0.05). The prediction results of bioinformatics websites have found 152 downstream target genes related to miR-29a, among which FBN1, MAP2K6, KPNB1, COL1A2, SNIP1, LAMC1, and SP1 genes may be related to the regulatory effect of miR-29a on TGF-ß1/Smad3 signaling pathway. Conclusion: miR-29a may affect lung fibrosis induced by rare earth Nd(2)O(3) exposure in mice by regulating TGF-ß1/Smad3 signaling pathway. Overexpression of miR-29a may inhibit TGF-ß1/Smad3 signaling pathway and reduce the degree of pulmonary fibrosis in mice.

Cardiovascular Mortality, Habitual Exercise, and Particulate Matter 2.5 Exposure: A Longitudinal Cohort Study.

INTRODUCTION: Habitual exercise may amplify the respiratory uptake of air pollutants in the lung, exacerbating the adverse effects of air pollution. However, it is unclear whether this can reduce the health benefits of habitual exercise (referred to as leisure-time exercise). Thus, the combined effects of habitual exercise and chronic exposure to ambient fine particulate matter 2.5 on cardiovascular mortality were examined among adults in Taiwan. METHODS: A total of 384,128 adults were recruited between 2001 and 2016 and followed up to May 31, 2019. Participants' vital status was obtained by matching their unique identification numbers with records of cardiovascular death in the National Death Registry of Taiwan. A time-varying Cox regression model was used to analyze the data. Analyses were conducted in 2021. RESULTS: Cardiovascular death risks were inversely associated with habitual exercise and positively associated with chronic exposure to particulate matter 2.5. The beneficial effects of habitual exercise on cardiovascular mortality were not modified by chronic exposure to particulate matter 2.5. Inactive participants with high particulate matter 2.5 exposure exhibited a 123% higher risk of cardiovascular death than high-exercise-group participants exposed to low levels of particulate matter 2.5 (95% CI=89, 163). CONCLUSIONS: High level of habitual exercise combined with low exposure level of ambient particulate matter 2.5 is associated with the lowest risk of cardiovascular death. A higher level of habitual exercise is associated with a lower risk of cardiovascular death at all levels of particulate matter 2.5 exposure studied. The results indicate that habitual exercise is a safe health promotion strategy even for people residing in relatively polluted regions.

Transition practice before entering primary school: A longitudinal study of children with and without special needs across a year.

INTRODUCTION: The transition to primary school is a significant milestone for children. Transition periods can offer new opportunities to build skills, relationships, and experiences that strengthen self-efficacy. In Singapore, parents play an important role in supporting transition as preschools and primary schools operate independently. Occupational therapists are involved in supporting children with special needs in transitions. OBJECTIVE: Focusing on the transition period of getting children ready for primary school, the objectives are (i) to learn about the strategies that parents used for the purpose of transition and understand the intentions behind what they do and (ii) to compare the transition practices and perceived school readiness between parents of children with and without special needs. METHOD: A longitudinal study involving 48 parents was conducted over 12 months. Parents completed a survey at the start and end of the year to detect changes from baseline, and semi-structured interviews every two months to gather their subjective experiences and track their child's readiness for transition. The surveys and interviews were conducted on a mobile instant messaging platform. Coding of responses was guided by school readiness domains identified in earlier studies and Occupational Therapy Practice Framework's approaches to intervention. RESULTS: Most parents focused on establishing and maintaining new self-help and academic skills across the year while few were "modifying" or "preventing". Increasing trends in child readiness were noted for both children with and without special needs. CONCLUSION: In family-centred practice, it is important to recognise parents' expertise and resources.

[Analysis of CT features of 15 children with 2019 novel coronavirus infection].

Objective: To explore imaging characteristics of children with 2019 novel coronavirus (2019-nCoV) infection. Methods: A retrospective analysis was performed on clinical data and chest CT images of 15 children diagnosed with 2019-nCoV infection. They were admitted to the Third People's Hospital of Shenzhen from January 16 to February 6, 2020. The distribution and morphology of pulmonary lesions on chest CT images were analyzed. Results: Among the 15 children, 5 were males and 10 females, aged from 4 to 14 years. Five of the 15 children were febrile and 10 were asymptomatic on the first visit. The first nasal or pharyngeal swab samples in all the 15 cases were positive for 2019-nCoV nucleic acid. For their first chest CT images, 6 patients had no lesions, while 9 patients had pulmonary inflammatory lesions. Seven cases had small nodular ground glass opacities and 2 cases had speckled ground glass opacities. After 3 to 5 days of treatment, 2019-nCoV nucleic acid in a second respiratory sample turned negative in 6 cases. Among them, chest CT images showed less lesions in 2 cases, no lesion in 3 cases, and no improvement in 1 case. The remaining 9 cases were still positive in a second nucleic acid test. Six patients showed similar chest CT inflammation, while 3 patients had new lesions, which were all small nodular ground glass opacities. Conclusions: The early chest CT images of children with 2019-nCoV infection are mostly small nodular ground glass opacities. The clinical symptoms of children with 2019-nCoV infection are nonspecific. Dynamic reexamination of chest CT and nucleic acid are important.

[Analysis of CT features of 15 Children with 2019 novel coronavirus infection].

Objective: To explore imaging characteristics of children with 2019 novel coronavirus (2019-nCoV) infection. Methods: A retrospective analysis was performed on clinical data and chest CT images of 15 children diagnosed with 2019-nCoV. They were admitted to the third people's Hospital of Shenzhen from January 16 to February 6, 2020. The distribution and morphology of pulmonary lesions on chest CT images were analyzed. Results: Among the 15 children, there were 5 males and 10 females, aged from 4 to 14 years old. Five of the 15 children were febrile and 10 were asymptomatic on first visit. The first nasal or pharyngeal swab samples in all the 15 cases were positive for 2019-nCoV nucleic acid. For their first chest CT images, 6 patients had no lesions, while 9 patients had pulmonary inflammation lesions. Seven cases of small nodular ground glass opacities and 2 cases of speckled ground glass opacities were found. After 3 to 5 days of treatment, 2019-nCoV nucleic acid in a second respiratory sample turned negative in 6 cases. Among them, chest CT images showed less lesions in 2 cases, no lesion in 3 cases, and no improvement in 1 case. Other 9 cases were still positive in a second nucleic acid test. Six patients showed similar chest CT inflammation, while 3 patients had new lesions, which were all small nodular ground glass opacities. Conclusions: The early chest CT images of children with 2019-nCoV infection are mostly small nodular ground glass opacities. The clinical symptoms of children with 2019-nCoV infection are nonspecific. Dynamic reexamination of chest CT and nucleic acid are important.

Ductile Zr-Based Bulk Metallic Glasses by Controlling Heterogeneous Microstructure from Phase Competition Strategy.

In this paper, we prepare the alloys of Zr41.2Ti13.8Cu12.5Ni10Be22.5, Zr44.4Ti14.8Cu14.3Ni11.5Be15, and Zr38Ti12.7Cu9.6Ni7.7Be32 to show the effects of alloy composition on the inhomogeneity structures and mechanical properties of Zr-based bulk metallic glasses (BMGs). Compared with the best glass former Zr41.2Ti13.8Cu12.5Ni10Be22.5, some nanoscale inhomogeneity structures can be induced by shifting the compositions towards a primary phase in the alloys of Zr44.4Ti14.8Cu14.3Ni11.5Be15 and Zr38Ti12.7Cu9.6Ni7.7Be32. The room temperature compression tests reveal that theBMGs contained nanoscale inhomogeneity structures exhibit superior mechanical properties with the high strength of 1780 MPa and especially a remarkable plastic strain of over 9%. These findings provide a new perspective to enhance the ductility of BMGs by introducing nanoscale inhomogeneity structures based on the phase competition strategy.

Isolation of Cardiomyocytes Undergoing Mitosis With Complete Cytokinesis.

RATIONALE: Adult human cardiomyocytes do not complete cytokinesis despite passing through the S-phase of the cell cycle. As a result, polyploidization and multinucleation occur. To get a deeper understanding of the mechanisms surrounding division of cardiomyocytes, there is a crucial need for a technique to isolate cardiomyocytes that complete cell division/cytokinesis. OBJECTIVE: Markers of cell cycle progression based on DNA content cannot distinguish between mitotic cardiomyocytes that fail to complete cytokinesis from those cells that undergo true cell division. With the use of molecular beacons (MBs) targeting specific mRNAs, we aimed to identify truly proliferative cardiomyocytes derived from human induced pluripotent stem cells. METHODS AND RESULTS: Fluorescence-activated cell sorting combined with MBs was performed to sort cardiomyocyte populations enriched for mitotic cells. Expressions of cell cycle specific genes were confirmed by means of reverse transcription-quantitative polymerase chain reaction and single-cell RNA sequencing (scRNA-seq) combined with gene signatures of cell cycle progression. We characterized the sorted groups by proliferation assays and time-lapse microscopy which confirmed the proliferative advantage of MB-positive cell populations relative to MB-negative and G2/M populations. Gene expression analysis revealed that the MB-positive cardiomyocyte subpopulation exhibited patterns consistent with the processes of nuclear division, chromosome segregation, and transition from M to G1 phase. The use of dual-MBs targeting CDC20 and SPG20 mRNAs enabled the enrichment of cytokinetic events (CDC20highSPG20high). Interestingly, cells that did not complete cytokinesis and remained binucleated were found to be CDC20lowSPG20high while polyploid cardiomyocytes that replicated DNA but failed to complete karyokinesis were found to be CDC20lowSPG20low. CONCLUSIONS: This study demonstrates a novel alternative to existing DNA content-based approaches for sorting cardiomyocytes with true mitotic potential that can be used to study the unique dynamics of cardiomyocyte nuclei during mitosis. Our technique for sorting live cardiomyocytes undergoing cytokinesis would provide a basis for future studies to uncover mechanisms underlying the development and regeneration of heart tissue.

Inkjet-printed stretchable and low voltage synaptic transistor array.

Wearable and skin electronics benefit from mechanically soft and stretchable materials to conform to curved and dynamic surfaces, thereby enabling seamless integration with the human body. However, such materials are challenging to process using traditional microelectronics techniques. Here, stretchable transistor arrays are patterned exclusively from solution by inkjet printing of polymers and carbon nanotubes. The additive, non-contact and maskless nature of inkjet printing provides a simple, inexpensive and scalable route for stacking and patterning these chemically-sensitive materials over large areas. The transistors, which are stable at ambient conditions, display mobilities as high as 30 cm2 V-1 s-1 and currents per channel width of 0.2 mA cm-1 at operation voltages as low as 1 V, owing to the ionic character of their printed gate dielectric. Furthermore, these transistors with double-layer capacitive dielectric can mimic the synaptic behavior of neurons, making them interesting for conformal brain-machine interfaces and other wearable bioelectronics.

Sensory quality characteristics with different beef quality grades and surface texture features assessed by dented area and firmness, and the relation to muscle fiber and bundle characteristics.

The main objective of this study was to compare the eating quality among the groups categorized by the Korean beef quality grade and texture feature of exposed muscle surface assessed by extent of dented areas and firmness. Additionally, this study also investigated the effects of fiber and bundle characteristics on texture feature to establish the cause of differences in muscle surface texture. Significant differences were observed in the sensory quality characteristics among the quality grades mainly determined by marbling score (P < 0.05). However, the coarse texture group with a dented surface required a higher initial force to penetrate meat (P < 0.001), was more difficult to break meat into fragments (P < 0.001), and had a higher amount of perceptible residue in the mouth (P < 0.01) compared to the fine texture group. These differences in the surface texture features between the fine and coarse groups could be explained by bundle area and fiber number per each bundle.

Nanoconfinement effects of chemically reduced graphene oxide nanoribbons on poly(vinyl chloride).

Polymeric nanocomposites with graphene-based nanocarbons (GNCs) have been extensively studied with emphasis on the percolation of nanofillers toward electrical, rheological, and mechanical reinforcement. In this study, we report an unusual indirect reinforcing phenomenon of highly defective GNCs dispersed in the poly(vinyl chloride) (PVC) matrix via densification of the polymer packing originating from nanoscale confinement. Herein, chemically reduced graphene oxide nanoribbons (C-rGONRs) are employed as a nanofiller. The inclusion of defective and oxygen-functionalized C-rGONRs resulted in a dramatic densification of the PVC host with extremely low C-rGONR loading, largely exceeding the theoretical calculation from a rule of mixture. Along with the densification, the glass transition temperature of PVC also increased by 28.6 °C at 0.1 wt% filler loading. Remarkably, the oxygen barrier property and mechanical toughness under tension for the PVC/C-rGONR nanocomposite were the maximum when the greatest densification occurred. The structure-property relationship of the nanocomposites has been discussed with an emphasis on the nanoscale confinement phenomenon.

Investigating validity evidence of the Malay translation of the Copenhagen Burnout Inventory.

INTRODUCTION: The Copenhagen Burnout Inventory (CBI) is a recent burnout measure with a focus on fatigue and exhaustion. It has three factors: personal burnout, work-related burnout, and client-related burnout. This study aimed to translate the CBI into the Malay language and to validate the translated version among a group of medical students. METHODS: The forward-backward translation was performed as per standard guidelines. The Malay version of CBI (CBI-M) was distributed to 32 medical students to assess face validity and later to 452 medical students to assess construct validity. The data analysis was performed by Microsoft Excel, SPSS and AMOS. RESULTS: The face validity index of CBI-M was more than 0.8. The three factors of CBI-M achieved good levels of goodness-of-fit indices (Cmin/df = 2.99, RMSEA = 0.066, GFI = 0.906, CFI = 0.938, NFI = 0.910, TLI = 0.925). The composite reliability values of the three factors ranged from 0.84 to 0.87. The Cronbach's alpha values of the three factors ranged from 0.83 to 0.87. CONCLUSIONS: This study supports the face and construct validity of the CBI-M with a high internal consistency.

Characterization of neural stem cells modified with hypoxia/neuron-specific VEGF expression system for spinal cord injury.

Spinal cord injury (SCI) is an incurable disease causing an ischemic environment and functional defect, thus a new therapeutic approach is needed for SCI treatment. Vascular endothelial growth factor (VEGF) is a potent therapeutic gene to treat SCI via angiogenesis and neuroprotection, and both tissue-specific gene expression and high gene delivery efficiency are important for successful gene therapy. Here we design the hypoxia/neuron dual-specific gene expression system (pEpo-NSE) and efficient gene delivery platform can be achieved by the combination ex vivo gene therapy with erythropoietin (Epo) enhancer, neuron-specific enolase (NSE) promoter and neural stem cells (NSCs). An in vitro model, NSCs transfected with pEpo-NSE were consistently and selectively overexpressing therapeutic genes in response to neural differentiation and hypoxic conditions. Also, in SCI model, ex vivo gene therapy using pEpo-NSE system with NSCs significantly enhanced gene delivery efficiency compared with pEpo-NSE system gene therapy alone. However, microarray analysis reveals that introducing exogenous pEpo-NSE and VEGF triggers biological pathways in NSCs such as glycolysis and signaling pathways such as Ras and mitogen-activated protein kinase, leading to cell proliferation, differentiation and apoptosis. Collectively, it indicates that the pEpo-NSE gene expression system works stably in NSCs and ex vivo gene therapy using pEpo-NSE system with NSCs improves gene expression efficiency. However, exogenously introduced pEpo-NSE system has an influence on gene expression profiles in NSCs. Therefore, when we consider ex vivo gene therapy for SCI, the effects of changes in gene expression profiles in NSCs on safety should be investigated.

Knowledge, attitudes and practice survey on Zika virus infection among pregnant women in Brunei Darussalam

Objective:To assess the knowledge, attitudes, and practices (KAP) on Zika virus infection among pregnant women in Brunei Darussalam by a cross-sectional survey.Methods:Between February and June 2017, we recruited 234 pregnant women from all government healthcare centres at Brunei-Muara district, using a modified systematic sampling approach. A pre-tested and self-administered questionnaire was used and data analysis was conducted using descriptive statistics and multiple logistic regression analyses.Results:The study participants were mainly Malay (87.2%) and their mean age was 28.0 years. The median knowledge score was 13, out of a possible score of 28. Most participants (92.7%) knew that Zika virus was transmitted by mosquito bites whereas some (34.6%) knew that sexual transmission was also possible. Media (radio, television or newspapers) was the preferred source of updated information on Zika virus, followed by healthcare workers (44.0%), government announcements (43.2%), and social media (38.0%). Pregnant women who were 25 years old or older [Adj. OR=3.62 (95% CI: 1.57, 9.51)], not Malays [Adj. OR=3.32 (95% CI: 1.35, 8.55)], and had an average monthly household income of more than BND $3 000 [Adj. OR=4.06 (95% CI: 1.81, 19.44)] were more likely to score higher for knowledge on Zika virus. The median prevention practice score was 23, out of a possible score of 36. Most participants reported wearing covering clothes (98.3%) and kept their living surroundings clean (99.6%). Most participants (88.0%) agreed that Zika is an important issue in their community.Conclusion:We found a lack of knowledge on Zika virus infection among pregnant women attending government maternal and child healthcare centres in Brunei Darussalam, in particular that Zika virus can be sexually transmitted. Such information could be well disseminated at the healthcare centre level. Health literacy studies should be conducted to understand the facilitators and barriers of KAP on Zika virus infection among pregnant women.

Capsaicin attenuates spermatogenic cell death induced by scrotal hyperthermia through its antioxidative and anti-apoptotic activities.

This study was performed to examine whether capsaicin, the main pungent ingredient of red peppers, exerts protective effects against testicular injuries induced by transient scrotal hyperthermia. Capsaicin (0.33 mg kg-1 ) was administered subcutaneously to mice one hour before heat stress (HS) in a 43°C water bath for 20 min. After 7 days, mice exposed to HS showed low testicular weight, severe vacuolisation of seminiferous tubules followed by loss of spermatogenic cells, and appearance of multinucleated giant cells and remarkable TUNEL-positive apoptotic cells, as well as weak immunoreactivity of phospholipid hydroperoxide glutathione peroxidase (PHGPx) in spermatogenic cells. Levels of lipid peroxidation and heat shock 70-kDa protein 1 (Hsp72) and BCL2-associated X protein (Bax) mRNA were greatly increased, but PHGPx, manganese superoxide dismutase (MnSOD), and B-cell lymphoma-extra large (Bcl-xL) mRNAs were significantly diminished in the testes by HS. However, capsaicin pre-treatment significantly suppressed the spermatogenic cell death, oxidative stress (levels of MDA, PHGPx immunoreactivity, and Hsp72, PHGPx, and MnSOD mRNA) and apoptosis (levels of TUNEL-positive cells, and Bcl-xL and Bax mRNA) in testes by HS. These suggest that capsaicin has a protective effect against spermatogenic cell death induced by scrotal hyperthermia through its antioxidative and anti-apoptotic activities.

Effects of Per-diem payment on the duration of hospitalization and medical expenses according to the palliative care demonstration project in Korea.

OBJECTIVES: The aim of this study was to examine the impacts of a government-directed palliative care demonstration (PCD) project, Per-diem Payment System (PDPS), on length of stay (LOS), hospital costs, resource usage and healthcare quality during the searched period from January in 2009 to December in 2010. STUDY DESIGN: A retrospective claim data review. METHODS: Individuals who had been eligible for the palliative care payment policy, PDPS, during 2 years (from 2009 to 2010) were assigned to the case group including seven hospitals (n = 3117). Those (seven hospitals) who were not come eligible for the palliative care payment policy were assigned to the control group (n = 2347) with fee for service. The data used in this study were electronically submitted requests of payment to the Health Insurance Review Agency during the period January 2009 to December 2010. RESULTS: After the PCD project, the length of stay for palliative patients with cancer diseases decreased by 2.56% (ß = -0.026; p-value = 0.0001) among patients hospitalized in a PCD project compared with patients hospitalized in seven hospitals that was not designed as a PCD project. Compared with costs before the PCD project, costs decreased by 0.76% (ß = 0.013; p-value = 0.0001). CONCLUSIONS: We provided evidence regarding the change in the societal burden due to palliative care. Although there was a reduction of direct medical costs reported in limited number of hospitals, in the long term, we can anticipate an expanding impact on medical costs in all palliative hospitals. Copyright © 2016 John Wiley & Sons, Ltd.

Prevalence and Clinical Relevance of Exon 2 Deletion of COMMD1 in Bedlington Terriers in Korea.

BACKGROUND: Deletion of exon 2 of copper metabolism domain containing 1 (COMMD1) results in copper toxicosis in Bedlington terriers (CT-BT). OBJECTIVES: This study was conducted to identify the prevalence and clinical relevance of the COMMD1 mutation in Bedlington terriers in Korea. ANIMALS: A total of 105 purebred Bedlington terriers (50 males, 55 females) from the kennels and pet dog clubs in Korea were examined during the period 2008-2013. METHODS: A multiplex PCR was carried out to detect exon 2 deletion of COMMD1. Clinical analysis was performed on each genetic group, and clinical status of the dogs was followed up to estimate survival probability. RESULTS: Of the 105 samples, 52 (49%) were wild-type homozygote, 47 (45%) were heterozygote, and 6 (6%) were mutant-type homozygote. Plasma alanine aminotransferase (ALT) activity was increased in the mutant-type homozygous group >2 years of age (P < .0001). The survival probability of 6 mutant-type homozygotes surviving 2.5 years was 0.67, and 4 years was 0.5. CONCLUSIONS AND CLINICAL IMPORTANCE: Results show the prevalence and clinical relevance of exon 2 deletion of COMMD1 and could help establish a structured selective breeding program to prevent CT-BT in Korea.

Generation of RUNX3 knockout pigs using CRISPR/Cas9-mediated gene targeting.

Pigs are an attractive animal model to study the progression of cancer because of their anatomical and physiological similarities to human. However, the use of pig models for cancer research has been limited by availability of genetically engineered pigs which can recapitulate human cancer progression. Utilizing genome editing technologies such as CRISPR/Cas9 system allows us to generate genetically engineered pigs at a higher efficiency. In this study, specific CRISPR/Cas9 systems were used to target RUNX3, a known tumour suppressor gene, to generate a pig model that can induce gastric cancer in human. First, RUNX3 knockout cell lines carrying genetic modification (monoallelic or biallelic) of RUNX3 were generated by introducing engineered CRISPR/Cas9 system specific to RUNX3 into foetal fibroblast cells. Then, the genetically modified foetal fibroblast cells were used as donor cells for somatic cell nuclear transfer, followed by embryo transfer. We successfully obtained four live RUNX3 knockout piglets from two surrogates. The piglets showed the lack of RUNX3 protein in their internal organ system. Our results demonstrate that the CRISPR/Cas9 system is effective in inducing mutations on a specific locus of genome and the RUNX3 knockout pigs can be useful resources for human cancer research and to develop novel cancer therapies.

Natural history and factors associated with ulnar-sided wrist pain in distal radial fractures treated by plate fixation.

UNLABELLED: We documented longitudinal changes in the incidence of ulnar-sided wrist pain after distal radial fractures treated by plate fixation and identified factors associated with ulnar-sided wrist pain. A total of 140 patients were enrolled in this study. Radiographs were taken 3 months after operation, and were used to measure radial inclination, anterior angulation and ulnar variance, and to identify the presence of an ulnar styloid fracture. Clinical assessments at the same time included grip strengths, ranges of wrist motion and the patient-rated wrist evaluation questionnaire. The presence of ulnar-sided wrist pain was noted at each follow-up visit. The incidence of ulnar-sided wrist pain decreased significantly with time after surgery (22 patients at 3 months, 11 patients at 6 months and three patients at 12 months). The mean age, sex, the presence of an ulnar styloid fracture and the classification of the distal radial fracture were not factors that were associated with a higher incidence of ulnar-sided wrist pain, but there was an association between higher patient-rated wrist evaluation scores and the presence of ulnar-sided wrist pain. LEVEL OF EVIDENCE: Prognosis, Level IV.