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1.
Foods ; 13(15)2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39123516

RESUMO

This study compared the quality of hand-shaken green tea prepared through rapid and natural cooling methods. Cooling is crucial in preserving green tea's flavor, aroma, and nutritional components. In the rapid cooling method, green tea is freshly brewed at an initial temperature of 95 °C for 25 min, and then rapidly cooled to 18 °C for 25 min. Conversely, the natural cooling method involves brewing tea at the same initial temperature and time, but allowing it to cool gradually to 30 °C over approximately 4-5 h at room temperature. This study's findings indicate that the rapid cooling method produced green tea with a more vibrant color and improved clarity versus the natural cooling method. Sensory analysis revealed that the taste and aroma of the hand-shaken green tea prepared using rapid cooling were perceived to be more refreshing and invigorating. However, the natural cooling method preserved a higher level of chemical components, including individual catechin caffeine, total polyphenol, soluble solids, reducing sugar, and total tannins. The essential amino acid content of the rapidly and naturally cooled green tea infusions was 6.85 and 13.55 µg/mL, respectively. The γ-Aminobutyric acid (GABA) content was 439.82 and 457.31 µg/mL, respectively. This study's findings suggest that rapid cooling during the preparation of hand-shaken green tea enhances its overall quality. The vibrant color, improved clarity, refreshing taste, and invigorating aroma make it a preferable choice for tea enthusiasts who seek an enhanced sensory experience and excellent quality.

2.
Global Spine J ; : 21925682231162817, 2024 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-39069660

RESUMO

STUDY DESIGN: A systemic review and a meta-analysis. We also provided a retrospective cohort for validation in this study. OBJECTIVE: (1) Using a meta-analysis to determine the pooled discriminatory ability of The Skeletal Oncology Research Group (SORG) classical algorithm (CA) and machine learning algorithms (MLA); and (2) test the hypothesis that SORG-CA has less variability in performance than SORG-MLA in non-American validation cohorts as SORG-CA does not incorporates regional-specific variables such as body mass index as input. METHODS: After data extraction from the included studies, logit-transformation was applied for extracted AUCs for further analysis. The discriminatory abilities of both algorithms were directly compared by their logit (AUC)s. Further subgroup analysis by region (America vs non-America) was also conducted by comparing the corresponding logit (AUC). RESULTS: The pooled logit (AUC)s of 90-day SORG-CA was .82 (95% confidence interval [CI], .53-.11), 1-year SORG-CA was 1.11 (95% CI, .74-1.48), 90-day SORG-MLA was 1.36 (95% CI, 1.09-1.63), and 1-year SORG-MLA was 1.57 (95% CI, 1.17-1.98). All the algorithms performed better in United States than in Taiwan (P < .001). The performance of SORG-CA was less influenced by a non-American cohort than SORG-MLA. CONCLUSION: These observations might highlight the importance of incorporating region-specific variables into existing models to make them generalizable to racially or geographically distinct regions.

3.
Artigo em Inglês | MEDLINE | ID: mdl-39051924

RESUMO

BACKGROUND: Survival estimation for patients with symptomatic skeletal metastases ideally should be made before a type of local treatment has already been determined. Currently available survival prediction tools, however, were generated using data from patients treated either operatively or with local radiation alone, raising concerns about whether they would generalize well to all patients presenting for assessment. The Skeletal Oncology Research Group machine-learning algorithm (SORG-MLA), trained with institution-based data of surgically treated patients, and the Metastases location, Elderly, Tumor primary, Sex, Sickness/comorbidity, and Site of radiotherapy model (METSSS), trained with registry-based data of patients treated with radiotherapy alone, are two of the most recently developed survival prediction models, but they have not been tested on patients whose local treatment strategy is not yet decided. QUESTIONS/PURPOSES: (1) Which of these two survival prediction models performed better in a mixed cohort made up both of patients who received local treatment with surgery followed by radiotherapy and who had radiation alone for symptomatic bone metastases? (2) Which model performed better among patients whose local treatment consisted of only palliative radiotherapy? (3) Are laboratory values used by SORG-MLA, which are not included in METSSS, independently associated with survival after controlling for predictions made by METSSS? METHODS: Between 2010 and 2018, we provided local treatment for 2113 adult patients with skeletal metastases in the extremities at an urban tertiary referral academic medical center using one of two strategies: (1) surgery followed by postoperative radiotherapy or (2) palliative radiotherapy alone. Every patient's survivorship status was ascertained either by their medical records or the national death registry from the Taiwanese National Health Insurance Administration. After applying a priori designated exclusion criteria, 91% (1920) were analyzed here. Among them, 48% (920) of the patients were female, and the median (IQR) age was 62 years (53 to 70 years). Lung was the most common primary tumor site (41% [782]), and 59% (1128) of patients had other skeletal metastases in addition to the treated lesion(s). In general, the indications for surgery were the presence of a complete pathologic fracture or an impending pathologic fracture, defined as having a Mirels score of ≥ 9, in patients with an American Society of Anesthesiologists (ASA) classification of less than or equal to IV and who were considered fit for surgery. The indications for radiotherapy were relief of pain, local tumor control, prevention of skeletal-related events, and any combination of the above. In all, 84% (1610) of the patients received palliative radiotherapy alone as local treatment for the target lesion(s), and 16% (310) underwent surgery followed by postoperative radiotherapy. Neither METSSS nor SORG-MLA was used at the point of care to aid clinical decision-making during the treatment period. Survival was retrospectively estimated by these two models to test their potential for providing survival probabilities. We first compared SORG to METSSS in the entire population. Then, we repeated the comparison in patients who received local treatment with palliative radiation alone. We assessed model performance by area under the receiver operating characteristic curve (AUROC), calibration analysis, Brier score, and decision curve analysis (DCA). The AUROC measures discrimination, which is the ability to distinguish patients with the event of interest (such as death at a particular time point) from those without. AUROC typically ranges from 0.5 to 1.0, with 0.5 indicating random guessing and 1.0 a perfect prediction, and in general, an AUROC of ≥ 0.7 indicates adequate discrimination for clinical use. Calibration refers to the agreement between the predicted outcomes (in this case, survival probabilities) and the actual outcomes, with a perfect calibration curve having an intercept of 0 and a slope of 1. A positive intercept indicates that the actual survival is generally underestimated by the prediction model, and a negative intercept suggests the opposite (overestimation). When comparing models, an intercept closer to 0 typically indicates better calibration. Calibration can also be summarized as log(O:E), the logarithm scale of the ratio of observed (O) to expected (E) survivors. A log(O:E) > 0 signals an underestimation (the observed survival is greater than the predicted survival); and a log(O:E) < 0 indicates the opposite (the observed survival is lower than the predicted survival). A model with a log(O:E) closer to 0 is generally considered better calibrated. The Brier score is the mean squared difference between the model predictions and the observed outcomes, and it ranges from 0 (best prediction) to 1 (worst prediction). The Brier score captures both discrimination and calibration, and it is considered a measure of overall model performance. In Brier score analysis, the "null model" assigns a predicted probability equal to the prevalence of the outcome and represents a model that adds no new information. A prediction model should achieve a Brier score at least lower than the null-model Brier score to be considered as useful. The DCA was developed as a method to determine whether using a model to inform treatment decisions would do more good than harm. It plots the net benefit of making decisions based on the model's predictions across all possible risk thresholds (or cost-to-benefit ratios) in relation to the two default strategies of treating all or no patients. The care provider can decide on an acceptable risk threshold for the proposed treatment in an individual and assess the corresponding net benefit to determine whether consulting with the model is superior to adopting the default strategies. Finally, we examined whether laboratory data, which were not included in the METSSS model, would have been independently associated with survival after controlling for the METSSS model's predictions by using the multivariable logistic and Cox proportional hazards regression analyses. RESULTS: Between the two models, only SORG-MLA achieved adequate discrimination (an AUROC of > 0.7) in the entire cohort (of patients treated operatively or with radiation alone) and in the subgroup of patients treated with palliative radiotherapy alone. SORG-MLA outperformed METSSS by a wide margin on discrimination, calibration, and Brier score analyses in not only the entire cohort but also the subgroup of patients whose local treatment consisted of radiotherapy alone. In both the entire cohort and the subgroup, DCA demonstrated that SORG-MLA provided more net benefit compared with the two default strategies (of treating all or no patients) and compared with METSSS when risk thresholds ranged from 0.2 to 0.9 at both 90 days and 1 year, indicating that using SORG-MLA as a decision-making aid was beneficial when a patient's individualized risk threshold for opting for treatment was 0.2 to 0.9. Higher albumin, lower alkaline phosphatase, lower calcium, higher hemoglobin, lower international normalized ratio, higher lymphocytes, lower neutrophils, lower neutrophil-to-lymphocyte ratio, lower platelet-to-lymphocyte ratio, higher sodium, and lower white blood cells were independently associated with better 1-year and overall survival after adjusting for the predictions made by METSSS. CONCLUSION: Based on these discoveries, clinicians might choose to consult SORG-MLA instead of METSSS for survival estimation in patients with long-bone metastases presenting for evaluation of local treatment. Basing a treatment decision on the predictions of SORG-MLA could be beneficial when a patient's individualized risk threshold for opting to undergo a particular treatment strategy ranged from 0.2 to 0.9. Future studies might investigate relevant laboratory items when constructing or refining a survival estimation model because these data demonstrated prognostic value independent of the predictions of the METSSS model, and future studies might also seek to keep these models up to date using data from diverse, contemporary patients undergoing both modern operative and nonoperative treatments. LEVEL OF EVIDENCE: Level III, diagnostic study.

4.
J Clin Invest ; 134(10)2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38747285

RESUMO

Transforming growth factor ß (TGF-ß) signaling is a core pathway of fibrosis, but the molecular regulation of the activation of latent TGF-ß remains incompletely understood. Here, we demonstrate a crucial role of WNT5A/JNK/ROCK signaling that rapidly coordinates the activation of latent TGF-ß in fibrotic diseases. WNT5A was identified as a predominant noncanonical WNT ligand in fibrotic diseases such as systemic sclerosis, sclerodermatous chronic graft-versus-host disease, and idiopathic pulmonary fibrosis, stimulating fibroblast-to-myofibroblast transition and tissue fibrosis by activation of latent TGF-ß. The activation of latent TGF-ß requires rapid JNK- and ROCK-dependent cytoskeletal rearrangements and integrin αV (ITGAV). Conditional ablation of WNT5A or its downstream targets prevented activation of latent TGF-ß, rebalanced TGF-ß signaling, and ameliorated experimental fibrosis. We thus uncovered what we believe to be a novel mechanism for the aberrant activation of latent TGF-ß in fibrotic diseases and provided evidence for targeting WNT5A/JNK/ROCK signaling in fibrotic diseases as a new therapeutic approach.


Assuntos
Fibroblastos , Fibrose , Fator de Crescimento Transformador beta , Proteína Wnt-5a , Quinases Associadas a rho , Proteína Wnt-5a/metabolismo , Proteína Wnt-5a/genética , Animais , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/genética , Camundongos , Humanos , Fibroblastos/metabolismo , Fibroblastos/patologia , Quinases Associadas a rho/metabolismo , Quinases Associadas a rho/genética , Escleroderma Sistêmico/patologia , Escleroderma Sistêmico/metabolismo , Escleroderma Sistêmico/genética , Camundongos Knockout , Proteínas Wnt/metabolismo , Proteínas Wnt/genética , Sistema de Sinalização das MAP Quinases , Miofibroblastos/metabolismo , Miofibroblastos/patologia , Transdução de Sinais , Fibrose Pulmonar Idiopática/patologia , Fibrose Pulmonar Idiopática/metabolismo , Fibrose Pulmonar Idiopática/genética
5.
Food Chem X ; 21: 101227, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38420504

RESUMO

Ginger-infused sesame oil enriches the nutrition and provides enhanced flavor for the foods. An original processing procedure and module for evaluation were established in this study, using different raw materials (Guangdong and Chu ginger) and treatments (ginger powder, extract, and both). The quality, functionality, and flavor of the infused oils were evaluated. Ginger-infused sesame oil contained 0.58-3.22 µg/g of 6-gingerol, 0.21-0.88 µg/g of 6-shogaol. The number range of volatile compounds from 48 to 55 identified by gas chromatography-mass spectrometry varies depending on different process procedures. Agglomerative hierarchical clustering analysis revealed the flavor profiles were clustered by different varieties, while gingerol and phytosterol was by different treatments. In conclusion, sesame oil was an appropriate carrier for gingerol and phytosterol, which are characterized by higher antioxidant capacities (p < 0.05). These results show the benefits of developing infused oil products with enhanced functional and sensory properties.

6.
J Clin Med ; 12(24)2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38137740

RESUMO

BACKGROUND: The distal radius fracture is a common orthopedic injury. We aimed to share the surgical steps and investigate the outcomes of treating distal radius fractures with wounds ≤10 mm using a globally accessible locking plate. METHODS: We collected 46 patients who underwent surgery via a <10 mm wound, with a control group consisting of 40 patients who underwent conventional procedures. Both groups were treated using the same volar plate. We compared the radiographic reduction quality, including volar tilt angle, radial inclination angle, and ulna variance. Additionally, clinical outcomes, such as pain assessed using VAS, Q-Dash score, and PRWE, were evaluated. Patient satisfaction with the wound was also analyzed. The follow-up time for the clinical outcomes was 24.2 ± 13.47 months. RESULTS: There were no differences in the quality of reduction in parameters such as the volar tilt angle (p = 0.762), radial inclination angle (p = 0.986), and ulna variance (p = 0.166). Both groups exhibited comparable results in pain VAS (p = 0.684), Q-Dash score (p = 0.08), and PRWE (p = 0.134). The ≤10 mm incision group displayed an increase in satisfaction with the wound (p < 0.001). CONCLUSIONS: Treating distal radius fractures with a <10 mm wound using a non-specialized locking plate is a feasible approach. It does not compromise the quality of fracture reduction or functional scores and improves wound satisfaction.

7.
J Cell Biol ; 222(10)2023 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-37584589

RESUMO

Mitochondria are dynamic organelles regulated by fission and fusion processes. The fusion of membranes requires elaborative coordination of proteins and lipids and is particularly crucial for the function and quality control of mitochondria. Phosphatidic acid (PA) on the mitochondrial outer membrane generated by PLD6 facilitates the fusion of mitochondria. However, how PA promotes mitochondrial fusion remains unclear. Here, we show that a mitochondrial outer membrane protein, NME3, is required for PLD6-induced mitochondrial tethering or clustering. NME3 is enriched at the contact interface of two closely positioned mitochondria depending on PLD6, and NME3 binds directly to PA-exposed lipid packing defects via its N-terminal amphipathic helix. The PA binding function and hexamerization confer NME3 mitochondrial tethering activity. Importantly, nutrient starvation enhances the enrichment efficiency of NME3 at the mitochondrial contact interface, and the tethering ability of NME3 contributes to fusion efficiency. Together, our findings demonstrate NME3 as a tethering protein promoting selective fusion between PLD6-remodeled mitochondria for quality control.


Assuntos
Mitocôndrias , Nucleosídeo NM23 Difosfato Quinases , Ácidos Fosfatídicos , Fosfolipase D , Humanos , Mitocôndrias/metabolismo , Dinâmica Mitocondrial , Membranas Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Nucleosídeo NM23 Difosfato Quinases/metabolismo , Ácidos Fosfatídicos/metabolismo , Fosfolipase D/metabolismo
8.
Artigo em Inglês | MEDLINE | ID: mdl-37306629

RESUMO

BACKGROUND: The Skeletal Oncology Research Group machine-learning algorithm (SORG-MLA) was developed to predict the survival of patients with spinal metastasis. The algorithm was successfully tested in five international institutions using 1101 patients from different continents. The incorporation of 18 prognostic factors strengthens its predictive ability but limits its clinical utility because some prognostic factors might not be clinically available when a clinician wishes to make a prediction. QUESTIONS/PURPOSES: We performed this study to (1) evaluate the SORG-MLA's performance with data and (2) develop an internet-based application to impute the missing data. METHODS: A total of 2768 patients were included in this study. The data of 617 patients who were treated surgically were intentionally erased, and the data of the other 2151 patients who were treated with radiotherapy and medical treatment were used to impute the artificially missing data. Compared with those who were treated nonsurgically, patients undergoing surgery were younger (median 59 years [IQR 51 to 67 years] versus median 62 years [IQR 53 to 71 years]) and had a higher proportion of patients with at least three spinal metastatic levels (77% [474 of 617] versus 72% [1547 of 2151]), more neurologic deficit (normal American Spinal Injury Association [E] 68% [301 of 443] versus 79% [1227 of 1561]), higher BMI (23 kg/m2 [IQR 20 to 25 kg/m2] versus 22 kg/m2 [IQR 20 to 25 kg/m2]), higher platelet count (240 × 103/µL [IQR 173 to 327 × 103/µL] versus 227 × 103/µL [IQR 165 to 302 × 103/µL], higher lymphocyte count (15 × 103/µL [IQR 9 to 21× 103/µL] versus 14 × 103/µL [IQR 8 to 21 × 103/µL]), lower serum creatinine level (0.7 mg/dL [IQR 0.6 to 0.9 mg/dL] versus 0.8 mg/dL [IQR 0.6 to 1.0 mg/dL]), less previous systemic therapy (19% [115 of 617] versus 24% [526 of 2151]), fewer Charlson comorbidities other than cancer (28% [170 of 617] versus 36% [770 of 2151]), and longer median survival. The two patient groups did not differ in other regards. These findings aligned with our institutional philosophy of selecting patients for surgical intervention based on their level of favorable prognostic factors such as BMI or lymphocyte counts and lower levels of unfavorable prognostic factors such as white blood cell counts or serum creatinine level, as well as the degree of spinal instability and severity of neurologic deficits. This approach aims to identify patients with better survival outcomes and prioritize their surgical intervention accordingly. Seven factors (serum albumin and alkaline phosphatase levels, international normalized ratio, lymphocyte and neutrophil counts, and the presence of visceral or brain metastases) were considered possible missing items based on five previous validation studies and clinical experience. Artificially missing data were imputed using the missForest imputation technique, which was previously applied and successfully tested to fit the SORG-MLA in validation studies. Discrimination, calibration, overall performance, and decision curve analysis were applied to evaluate the SORG-MLA's performance. The discrimination ability was measured with an area under the receiver operating characteristic curve. It ranges from 0.5 to 1.0, with 0.5 indicating the worst discrimination and 1.0 indicating perfect discrimination. An area under the curve of 0.7 is considered clinically acceptable discrimination. Calibration refers to the agreement between the predicted outcomes and actual outcomes. An ideal calibration model will yield predicted survival rates that are congruent with the observed survival rates. The Brier score measures the squared difference between the actual outcome and predicted probability, which captures calibration and discrimination ability simultaneously. A Brier score of 0 indicates perfect prediction, whereas a Brier score of 1 indicates the poorest prediction. A decision curve analysis was performed for the 6-week, 90-day, and 1-year prediction models to evaluate their net benefit across different threshold probabilities. Using the results from our analysis, we developed an internet-based application that facilitates real-time data imputation for clinical decision-making at the point of care. This tool allows healthcare professionals to efficiently and effectively address missing data, ensuring that patient care remains optimal at all times. RESULTS: Generally, the SORG-MLA demonstrated good discriminatory ability, with areas under the curve greater than 0.7 in most cases, and good overall performance, with up to 25% improvement in Brier scores in the presence of one to three missing items. The only exceptions were albumin level and lymphocyte count, because the SORG-MLA's performance was reduced when these two items were missing, indicating that the SORG-MLA might be unreliable without these values. The model tended to underestimate the patient survival rate. As the number of missing items increased, the model's discriminatory ability was progressively impaired, and a marked underestimation of patient survival rates was observed. Specifically, when three items were missing, the number of actual survivors was up to 1.3 times greater than the number of expected survivors, while only 10% discrepancy was observed when only one item was missing. When either two or three items were omitted, the decision curves exhibited substantial overlap, indicating a lack of consistent disparities in performance. This finding suggests that the SORG-MLA consistently generates accurate predictions, regardless of the two or three items that are omitted. We developed an internet application (https://sorg-spine-mets-missing-data-imputation.azurewebsites.net/) that allows the use of SORG-MLA with up to three missing items. CONCLUSION: The SORG-MLA generally performed well in the presence of one to three missing items, except for serum albumin level and lymphocyte count (which are essential for adequate predictions, even using our modified version of the SORG-MLA). We recommend that future studies should develop prediction models that allow for their use when there are missing data, or provide a means to impute those missing data, because some data are not available at the time a clinical decision must be made. CLINICAL RELEVANCE: The results suggested the algorithm could be helpful when a radiologic evaluation owing to a lengthy waiting period cannot be performed in time, especially in situations when an early operation could be beneficial. It could help orthopaedic surgeons to decide whether to intervene palliatively or extensively, even when the surgical indication is clear.

9.
Global Spine J ; 13(4): 1112-1119, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-34096362

RESUMO

STUDY DESIGN: A retrospective cohort study. OBJECTIVE: To investigate the factors contributing to the development of postoperative distal junctional kyphosis (DJK) in adolescent idiopathic scoliosis (AIS) patients who underwent posterior spinal fusion (PSF) with lowest instrumented vertebrae (LIV) at or above L1. METHODS: Patients with Lenke type 1 or 2 curves who underwent PSF with LIV at or above L1 with a minimum follow-up of 2 years were evaluated. The primary outcome measure was the occurrence of postoperative DJK. Radiographic parameters of sagittal alignment and inclusion/exclusion of sagittal stable vertebra (SSV) in PSF were analyzed to determine their associations with the occurrence of postoperative DJK. RESULTS: Overall, 122 patients (mean age: 15.1 ± 3.2 years) were included. The overall incidence of postoperative DJK was 6.6%. DJK was observed in 19.0% (8/42) of patients whose SSV was not included in PSF and not in patients with SSV included in PSF (n = 80). In the SSV-excluded group, univariate analysis found two significant risk factors for DJK: postoperative thoracic kyphosis (TK, T5-12) and postoperative thoracolumbar kyphosis (TLK, T11-L2). The ROC curve revealed that postoperative TK ≥ 25° and TLK ≥ 10° best predicted the occurrence of postoperative DJK in the SSV-excluded group. The incidence was significantly higher in cases with postoperative TK ≥ 25° or TLK ≥ 10° (7/13 = 53.8%) than in those with postoperative TK < 25° and TLK < 10° (1/29 = 3.4%). CONCLUSIONS: The current study revealed that postoperative TK ≥ 25° or postoperative TLK ≥ 10° with SSV excluded from PSF were related to DJK after PSF for Lenke type 1 and type 2 AIS. When the SSV is intended to be spared from PSF to save more motion segments, TK and TLK should be carefully evaluated and attained in a lesser magnitude (TK < 25°, TLK < 10°) after surgery.

10.
Am J Transl Res ; 15(12): 6701-6717, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38186977

RESUMO

OBJECTIVE: Ribonuclease P RNA component H1 (RPPH1) is a long non-coding RNA (lncRNA) associated with cancer progression. Higher RPPH1 expression in breast and cervical cancer samples than that in normal tissues were observed through the lncRNASNP2 database; therefore, silencing RPPH1 expression might be a potential strategy for cancer treatments, even though RPPH1 is also an RNA subunit of ribonuclease P involved in processing transfer RNA (tRNA) precursors and the effect of RPPH1 knockdown is not yet fully understood. METHODS: Differentially expressed genes (DEGs) were identified through RNA sequencing in each shRNA-transfected RPPH1 knockdown MDA-MB-231, RPPH1 knockdown HeLa cell, and respective control cells, then the gene ontology enrichment analysis was performed by IPA and MetaCore database according to these DEGs, with further in vitro experiments validating the effect of RPPH1 silencing in MDA-MB-231 and HeLa cells. RESULTS: Hundreds of down-regulated DEGs were identified in RPPH1 knockdown MDA-MB-231 and HeLa cells while bioinformatics analysis revealed that these genes were involved in pathways related to immune response and cancerogenesis. Compared to mock- and vector-transfected cells, the production of mature tRNAs, cell proliferation and migration capacity were inhibited in RPPH1-silenced HeLa and MDA-MB-231 cells. Additionally, RPPH1 knockdown promoted G1 cell cycle arrest mainly through the down-regulation of cyclin D1, although glycolytic pathways were only affected in RPPH1 knockdown HeLa cells but not MDA-MB-231 cells. CONCLUSION: This study demonstrated that knockdown RPPH1 affected tRNA production, cell proliferation and metabolism. Our findings might provide insight into the role of RPPH1 in tumor development.

11.
Anal Chem ; 94(51): 17779-17786, 2022 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-36519823

RESUMO

Self-organization facilitates the formation of specific structures as a result of constituent interactions. In this study, the bottom of a 600 nm hole array photoresist template, which was deposited with a hydrophobic atom transfer radical polymerization (ATRP) initiator, was wetted by treatment with oxygen plasma. After the removal of the photoresist template, ring patterns of the ATRP initiator were formed at the interface between the hydrophobic and wetting regions. Poly[2-(dimethylamino)ethyl methacrylate] (PDMAEMA) was grafted from the ring array of the initiator to immobilize gold nanoparticles (AuNPs) as a uniform ring array on a silicon substrate via repeated swelling/shrinking cycles. The localized surface plasmon resonance (LSPR) peak of the PDMAEMA-AuNP hybrid ring (PAHR) red-shifted after 12 swelling/shrinking cycles. In comparison to gold nanoparticles, scalable gold nanorings can effectively develop a variety of nanostructures to design LSPR-based sensors and optimize the sensing accuracy and stability. To detect epithelial cell adhesion molecules (EpCAM) during the structural change from a ring to a disk, antiEpCAM was anchored onto the PAHR as a biosensor during swelling/shrinking. The coupling of antiEpCAM and EpCAM led to asymptotical convergence from rings to disks as well as blue shifts of the LSPR peaks. Linear correlation between the blue shift and EpCAM concentration showed a limit of detection of ∼27 pg mL-1 and a linear range of 25-200 pg mL-1 for the detection of EpCAM within 30 min. The simple method of combining lithography and plasma technology provides a versatile platform for developing the scalable ring structure of AuNPs for highly sensitive and selective biosensing.


Assuntos
Nanopartículas Metálicas , Ressonância de Plasmônio de Superfície , Ressonância de Plasmônio de Superfície/métodos , Ouro/química , Molécula de Adesão da Célula Epitelial , Nanopartículas Metálicas/química
12.
Sci Rep ; 12(1): 18965, 2022 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-36347920

RESUMO

The determination of lumbopelvic alignment is essential for planning adult spinal deformity surgery and for ensuring favorable surgical outcomes. This prospective study investigated the correlation between the lumbar section of lumbar spine lordosis and increasing pelvic incidence in 324 Asian adults with a mean age of 55 ± 13 years (range: 20-80 years), comprising 115 male and 209 female volunteers. Participants were divided into three groups based on pelvic incidence (G1, G2, and G3 had pelvic incidence of < 45°, 45-55°, and ≥ 55°, respectively). We determined that distal and proximal lumbar lordosis contributed differentially to the increase in pelvic incidence, whereas the lordosis ratio of the L3-L4 and L4-L5 segments mostly remained constant. The mean contribution ratio of the segmental lordosis from L1 to S1 was as follows: L1-L2, 2.3%; L2-L3, 11.7%; L3-L4, 18.1%; L4-L5, 25.2%; and L5-S1, 42.7%. Pelvic incidence had a stronger correlation with proximal lumbar lordosis than did distal lumbar lordosis. The ratios of proximal lumbar lordosis to distal lumbar lordosis were 37.8% in G1, 45.8% in G2, and 55.9% in G3. These findings serve as a reference for future lumbar spine correction or fusion surgery for Asian adults.


Assuntos
Lordose , Fusão Vertebral , Adulto , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Lordose/diagnóstico por imagem , Lordose/epidemiologia , Lordose/cirurgia , Estudos Prospectivos , Posição Ortostática , Radiografia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Estudos Retrospectivos
13.
BMC Surg ; 22(1): 366, 2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36289500

RESUMO

BACKGROUND: Transforaminal Lumbar Interbody Fusion (TLIF) is commonly associated with higher complications and longer operative time. This study aims to evaluate the effectiveness, safety, and usability of a novel minimally invasive surgery (MIS) bone graft delivery device. METHODS: 73 consecutive patients with lumbar spondylosis, degenerative disc disease, spondylolisthesis, scoliosis or trauma were enrolled in this randomized controlled trial. Group 1 comprised 39 patients treated with the novel MIS bone graft delivery device. Group 2 consisted of 34 patients treated with the conventional system. The primary objective of the study was the assessment of the amount of bone graft delivery using the device. The secondary objectives were the effect of the device on operative time, pain relief, disability improvement, and bone fusion grade. RESULTS: Bone delivery amount was significantly higher in the MIS device group (6.7 ± 2.9 mL) compared to the conventional group (2.3 ± 0.5 mL), p < 0.001. Regarding the operation time, the MIS device group was associated significantly lower duration than the conventional group (p < 0.001). After a 3-month follow-up, 39.5% of the patients in the MIS device group and 3.5% of the patients in the conventional group were observed to achieve grade I fusion (complete fusion). There was a significant difference in fusion success rates (p < 0.01). CONCLUSION: The novel MIS bone graft delivery device was associated with successful bone delivery. Our MIS device provides promising modality with less operative time and higher bone fusion rates than conventional modalities. Trial Registration This trial was retrospectively registered on ClinicalTrials.gov (Registration date: 11/19/2021; Registration number: NCT05190055).


Assuntos
Fusão Vertebral , Espondilolistese , Humanos , Fusão Vertebral/métodos , Vértebras Lombares/cirurgia , Espondilolistese/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Duração da Cirurgia , Resultado do Tratamento , Estudos Retrospectivos
14.
J Clin Med ; 11(18)2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36143035

RESUMO

INTRODUCTION: Predicting survival time for patients with spinal metastases is important in treatment choice. Generally speaking, six months is a landmark cutoff point. Revised Tokuhashi score (RTS), the most widely used scoring system, lost its accuracy in predicting 6-month survival, gradually. Therefore, a more precise scoring system is urgently needed. OBJECTIVE: The aim of this study is to create a new scoring system with a higher accuracy in predicting 6-month survival based on the previously used RTS. METHODS: Data of 171 patients were examined to determine factors that affect prognosis (reference group), and the remaining (validation group) were examined to validate the reliability of a new score, adjusted Tokuhashi score (ATS). We compared their discriminatory abilities of the prediction models using area under receiver operating characteristic curve (AUC). RESULTS: Target therapy and the Z score of BMI (Z-BMI), which adjusted to the patients' sex and age, were additional independent prognostic factors. Patients with target therapy use are awarded 4 points. The Z score of BMI could be added directly to yield ATS. The AUCs were 0.760 for ATS and 0.636 for RTS in the validation group. CONCLUSION: Appropriate target therapy use can prolong patients' survival. Z-BMI which might reflect nutritional status is another important influencing factor. With the optimization, surgeons could choose a more individualized treatment for patients.

15.
Spine (Phila Pa 1976) ; 47(19): 1362-1371, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35867582

RESUMO

STUDY DESIGN: A retrospective cohort study. OBJECTIVE: To determine radiographic parameters, including the lowest instrumented vertebral (LIV) tilt, related to the postoperative magnitude and progression of residual lumbar curves (LCs) in adolescent idiopathic scoliosis patients who underwent posterior spinal fusion with LIV at or above L1. SUMMARY OF BACKGROUND DATA: Although several guidelines have been proposed for thoracic curve fusion, factors related to the postoperative magnitude and potential progression of unfused LCs remained undetermined. The effect of the LIV tilt on residual LCs is also unclear. MATERIALS AND METHODS: Patients with Lenke type 1 to 4 curves who underwent posterior spinal fusion with LIV at or above L1 with a minimum follow-up period of 2 years were evaluated. Prediction models for residual LCs were developed using multivariate linear regressions with selected radiographic parameters. Subgroup analyses, followed by sensitivity tests, were then performed for variables best predicting the progression of residual LCs. RESULTS: A total of 130 patients were included. Multivariate linear regression analysis showed that the immediate postoperative LIV-tilt angle was associated with the immediate postoperative LCs and the prediction model for residual LCs, with high accuracy ( R =0.93 and 0.77, respectively). Sensitivity tests revealed immediate postoperative LIV-tilt angle <10° and correction rate of main thoracic curve Cobb angle >53% as predictors for progression of residual LCs, and they reached moderate discrimination when combined together as one criterion (odds ratio=16.3, 95% confidence interval=5.3-50.1; sensitivity=89%, specificity=67%, positive predicted value=51%, negative predicted value=94%). CONCLUSION: The current study revealed that LIV tilt, as an operable factor during surgery, is not only a determinant in prediction models showing high correlation with the magnitude of postoperative LCs but a predictor for progression of residual LCs. "Immediate postoperative LIV-tilt angle <10° and correction rate of main thoracic curve Cobb angle >53%," as a united criterion, could serve as a predictor for progression of residual LCs.


Assuntos
Cifose , Escoliose , Fusão Vertebral , Adolescente , Progressão da Doença , Seguimentos , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Radiografia , Estudos Retrospectivos , Escoliose/diagnóstico por imagem , Escoliose/cirurgia , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/cirurgia , Resultado do Tratamento
16.
Exp Cell Res ; 417(2): 113219, 2022 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-35643179

RESUMO

Induction of differentiation sensitizes chronic myeloid leukemia (CML) cells to the BCR-ABL inhibitor imatinib by mechanisms that remain unknown. We previously identified the BCR-ABL downstream effector CD69 which inhibits imatinib-induced CML cell differentiation. Herein, we found that the erythroid differentiation inducers activin A and aclacinomycin A induced expression of erythroid markers (α-globin, ζ-globin, GATA-1, and glycophorin A) and simultaneously reduced CD69 levels in K562 CML cells. Blockade of p38MAPK by SB203580 and shRNA eliminated the inhibitory effect of activin A on the promoter, mRNA, and protein levels and positive cell population of CD69. CD69 overexpression inhibited activin A-induced erythroid marker expression. Pretreatment of K562 cells with activin A to induce differentiation followed by a subtoxic concentration of imatinib caused growth inhibition and apoptosis that was reduced by CD69 overexpression. Activin A also reduced the expression of CD69's potential downstream molecule metallothionein 2A (MT2A) via p38MAPK. MT2A-knockdown reduced CD69 inhibition of activin A-induced erythroid marker expression. Furthermore, MT2A-knockdown reduced CD69 inhibition of activin A-imatinib sequential treatment-mediated growth inhibition and apoptosis in K562 and BCR-ABL-expressing CD34+ cells. These results suggest that CD69 inhibits activin A induction of erythroid differentiation-mediated CML cell sensitivity to imatinib via MT2A. Therefore, activin A induction of erythroid differentiation sensitizes BCR-ABL-positive cells to imatinib by downregulating the erythroid differentiation suppressors CD69 and MT2A.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Proteínas Quinases p38 Ativadas por Mitógeno , Ativinas , Antígenos CD/metabolismo , Antígenos de Diferenciação de Linfócitos T/metabolismo , Apoptose , Diferenciação Celular , Resistencia a Medicamentos Antineoplásicos , Proteínas de Fusão bcr-abl/metabolismo , Humanos , Mesilato de Imatinib/farmacologia , Células K562 , Lectinas Tipo C/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Metalotioneína , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
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