3D bioprinted vascularized lung cancer organoid models with underlying disease capable of more precise drug evaluation.

Despite encouraging progress in the development ofin vitrocancer models,in vitrocancer models that simultaneously recapitulate the complexity of the tumor microenvironment and its diverse cellular components and genetic properties remain lacking. Here, an advanced vascularized lung cancer (LC) model is proposed, which includes patient-derived LC organoids (LCOs), lung fibroblasts, and perfusable vessels using 3D bioprinting technology. To better recapitulate the biochemical composition of native lung tissues, a porcine lung-derived decellularized extracellular matrix (LudECM) hydrogel was produced to offer physical and biochemical cues to cells in the LC microenvironment. In particular, idiopathic pulmonary fibrosis-derived lung fibroblasts were used to implement fibrotic niches similar to actual human fibrosis. It was shown that they increased cell proliferation and the expression of drug resistance-related genes in LCOs with fibrosis. In addition, changes in resistance to sensitizing targeted anti-cancer drugs in LCOs with fibrosis were significantly greater in LudECM than in that Matrigel. Therefore, assessment of drug responsiveness in vascularized LC models that recapitulate lung fibrosis can help determine the appropriate therapy for LC patients accompanied by fibrosis. Furthermore, it is expected that this approach could be utilized for the development of targeted therapies or the identification of biomarkers for LC patients accompanied by fibrosis.

Rice PIN Auxin Efflux Carriers Modulate the Nitrogen Response in a Changing Nitrogen Growth Environment.

Auxins play an essential role in regulating plant growth and adaptation to abiotic stresses, such as nutrient stress. Our current understanding of auxins is based almost entirely on the results of research on the eudicot Arabidopsis thaliana, however, the role of the rice PIN-FORMED (PIN) auxin efflux carriers in the regulation of the ammonium-dependent response remains elusive. Here, we analyzed the expression patterns in various organs/tissues and the ammonium-dependent response of rice PIN-family genes (OsPIN genes) via qRT-PCR, and attempted to elucidate the relationship between nitrogen (N) utilization and auxin transporters. To investigate auxin distribution under ammonium-dependent response after N deficiency in rice roots, we used DR5::VENUS reporter lines that retained a highly active synthetic auxin response. Subsequently, we confirmed that ammonium supplementation reduced the DR5::VENUS signal compared with that observed in the N-deficient condition. These results are consistent with the decreased expression patterns of almost all OsPIN genes in the presence of the ammonium-dependent response to N deficiency. Furthermore, the ospin1b mutant showed an insensitive phenotype in the ammonium-dependent response to N deficiency and disturbances in the regulation of several N-assimilation genes. These molecular and physiological findings suggest that auxin is involved in the ammonium assimilation process of rice, which is a model crop plant.

Assessing the quality of reports about randomized controlled trials of scalp acupuncture combined with another treatment for stroke.

BACKGROUND: This study was designed to assess the quality of reporting on randomized controlled trials (RCTs) of scalp acupuncture for the treatment of stroke. METHODS: The following 8 databases were systematically investigated from their inception to December 2015: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, National Institute of Informatics Scholarly and Academic Information Navigator, National Digital Science Library, Korean Traditional Knowledge Portal, and Korean Studies Information Service System. RCTs utilizing scalp acupuncture as an intervention for stroke were selected, and the quality of reports was assessed based on the Consolidated Standards of Reporting Trials 2010 statement (CONSORT) and Standards for Reporting Interventions in Controlled Trials of Acupuncture 2010 (STRICTA). For each study, the overall quality score (OQS) of 13 CONSORT items, a combined key methodological index score (MIS) of 5 CONSORT items, and the OQS of 17 STRICTA items were measured. RESULTS: The original reports of 63 RCTs were ultimately obtained, and the median CONSORT OQS was 7 (minimum 2, maximum 11). Particularly, the items 'trial design', 'sample size', 'ancillary analyses', and 'harms' had a positive rate of less than 10%. The median MIS was 1 (minimum 0, maximum 5), with 'allocation concealment and implementation' and 'intent-to-treat analysis (ITT) analysis' having a positive rate of less than 10%. The median STRICTA OQS was 11 (minimum 6, maximum 14), and only the items 'sample size' and 'intent-to-treat analysis' were reported, with a positive rate of less than 10%. The mean CONSORT OQS increased by approximately 0.81 for each 5-year period in which manuscripts were published (95% confidence interval: 0.43 to 1.19; p < 0.001). No variable was significantly associated with MIS in the ordinal regression model. CONCLUSION: The quality of reports on RCTs investigating scalp acupuncture treatment for stroke was moderate to low. Furthermore, reporting of some items was either insufficient or inadequate in the majority of studies. In order to improve and standardize the quality of RCTs investigating scalp acupuncture for stroke, CONSORT and STRICTA guidelines should be utilized more frequently.

Assessing the quality of reports about randomized controlled trials of scalp acupuncture treatment for vascular dementia.

BACKGROUND: This study aimed to evaluate the quality of reports about randomized controlled trials (RCTs) of scalp acupuncture (SA) for the treatment of vascular dementia (VD). METHOD: A systematic search of reports published through to December 2015 was performed in eight databases. The quality of RCTs that used SA as an intervention for VD was evaluated based on the 2010 Consolidated Standards for Reporting of Trials (CONSORT) and 2010 Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA) guidelines. Thirteen items from the CONSORT guideline were scored to give an overall quality score (OQS, range 0-13), and a combined key methodological index score (MIS) (range 0-5) of five key methodological items was measured. The OQS of 17 items from the STRICTA guideline (range 0-17) was also measured. RESULTS: In total, 26 reports were evaluated. The median OQS based on the CONSORT guideline was 8 (minimum 5, maximum 11), and "trial design," "sample size," "ancillary analyses," and "harms" had a positive rate of less than 10%. The median MIS was 2 (minimum 0, maximum 5), with "allocation concealment and implementation," "blinding," and "intent-to-treat analysis" having a positive rate of less than 15%. The median OQS based on the STRICTA guideline was 12 (minimum 8, maximum 14), with "extent to which treatment was varied (1c)," "number of needle insertions per subject per session (2a)," and "setting and context of treatment (4b)" having a positive rate of less than 10%. CONCLUSIONS: The overall quality of reports on RCTs of SA treatment for VD was moderate to low. The quality of methodological items was markedly lower than that of other items. The CONSORT and STRICTA guidelines should be used more frequently to standardize the quality of RCT reports of SA treatment for VD.

Inpatient treatment effect and Minnesota Multiphasic Personality Inventory characteristics of motor vehicle collision injuries in a traditional korean medicine hospital: Retrospective chart review.

OBJECTIVES: To examine the changes in pain, disability, and quality of life in motor vehicle collision injury (MVCI) patients after treatment with traditional Korean medicine (TKM), and to investigate the psychological characteristics of these patients. METHODS: Forty-one patients with MVCI were treated with TKM including acupuncture, pharmacopuncture, moxibustion, cupping, herbal medication, chuna manual therapy, and physical therapy. Numeric Rating Scale (NRS), Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), Neck Disability Index (NDI), Oswestry Disability Index (ODI), and Lysholm Knee Scoring Scale were assessed at admission and discharge. The Minnesota Multiphasic Personality Inventory (MMPI) was assessed at admission. RESULTS: After treatment, NRS scores for headache, cervical pain, and lumbar pain were significantly decreased (P<0.05); NDI, ODI scores were significantly decreased, and Lysholm score was signifificantly increased (P<0.05). The following SF-36 scores were signifificantly increased: physical and mental component summary, bodily pain, role-physical, role-emotional, social functioning, and mental health scores (all P<0.05). MMPI identifified 3-1 profifile conversion V shape. CONCLUSIONS: Treatment of MVCI with TKM provided effective management of complex symptoms such as pain, disability, and loss of quality of life. A comprehensive plan must be implemented for treatment and research in cases of MVCIs owing to the correlation between physical symptoms and psychological profifiles.

Scalp acupuncture and electromagnetic convergence stimulation for patients with cerebral infarction: study protocol for a randomized controlled trial.

BACKGROUND: Scalp acupuncture (SA) and repetitive transcranial magnetic stimulation (rTMS) are effective for treating cerebral infarction. This study aims to examine the efficacy and safety of SA and electromagnetic convergence stimulation (SAEM-CS), which was developed through collaboration between conventional medical physicians and doctors who practice traditional Korean medicine. SAEM-CS was designed to improve function in patients with cerebral infarction, compared to the improvement after conventional stroke rehabilitation, SA, and rTMS therapeutic approaches. METHODS/DESIGN: This study is a prospective, outcome assessor-blinded, randomized controlled clinical trial with a 1:1:1:1 allocation ratio. Participants with motion or sensory disabilities caused by a first-time cerebral infarction (n = 60) that had occurred within 1 month of the study onset will be randomly assigned to control, SA, rTMS, or SAEM-CS groups. All groups will receive two sessions of conventional rehabilitation treatment per day. The SA group will receive SA on the upper limb area of MS6 and MS7 (at the lesional hemisphere) for 20 min, the rTMS group will receive low-frequency rTMS (LF-rTMS) treatment on the hot spot of the M1 region (motor cortex at the contralesional hemisphere) for 20 min, and the SAEM-CS group will receive LF-rTMS over the contralesional M1 region hot spot while receiving simultaneous SA stimulation on the lesional upper limb area of MS6 and MS7 for 20 min. SA, rTMS, and SAEM-CS treatments will be conducted once/day, 5 days/week (excluding Saturdays and Sundays) for 3 weeks, for a total of 15 sessions. The primary outcome will be evaluated using the Fugl-Meyer Assessment, while other scales assessing cognitive function, activities of daily living, walking, quality of life, and stroke severity are considered secondary outcome measures. Outcome measurements will be conducted at baseline (before intervention), 3 weeks after the first intervention (end of intervention), and 4 weeks after intervention completion. DISCUSSION: This study aims to explore the efficacy and safety of SAEM-CS on cerebral infarction. Collaborative research combined traditional Korean and conventional medicines, which can be useful in developing new treatment technologies. TRIAL REGISTRATION: KCT0001768 . Registered on 14 January 2016.