Development and implementation of evidence-based, nurse-leading early warning model and healthcare quality improvement project for transplant-associated thrombotic microangiopathy: a mixed-methods, before-and-after study.

OBJECTIVE: The early identification and diagnosis of transplant-associated thrombotic microangiopathy (TA-TMA) are essential yet difficult in patients underwent hematopoietic stem cell transplantation (HSCT). To develop an evidence-based, nurse-leading early warning model for TA-TMA, and implement the healthcare quality review and improvement project. METHODS: This study was a mixed-methods, before-and-after study. The early warning model was developed based on quality evidence from literature search. The healthcare quality review and improvement project mainly included baseline investigation of nurse, improvement action and effectiveness evaluation. The awareness and knowledge of early parameter of TA-TMA among nurses and the prognosis of patients underwent HSCT were compared before and after the improvement. RESULTS: A total of 1 guideline, 1 evidence synthesis, 4 expert consensuses, 10 literature reviews, 2 diagnostic studies, and 9 case series were included in the best evidence. The early warning model including warning period, high-risk characteristics and early manifestation of TA-TMA was developed. The improvement action, including staff training and assessment, suspected TA-TMA identification and patient education, was implemented. The awareness and knowledge rate of early parameter of TA-TMA among nurses significantly improved after improvement action (100% vs. 26.7%, P < 0.001). The incidence of TA-TMA was similar among patients underwent HSCT before and after improvement action (2.8% vs. 1.2%, P = 0.643), while no fall event occurred after improvement action (0 vs. 1.2%, P < 0.001). CONCLUSION: The evidence-based early warning model and healthcare quality improvement project could enhance the awareness and knowledge of TA-TMA among healthcare providers and might improve the prognosis of patients diagnosed with TA-TMA.

Molecular mechanism of RBM14-mediated promotion of proliferation, migration, and invasion in osteosarcoma.

Background: Osteosarcoma (OS) is an exceptionally aggressive bone neoplasm that predominantly impacts the paediatric and adolescent population, exhibiting unfavourable prognosis. The importance of RNA binding motif protein 14 (RBM14) in the aetiology of OS is not well understood, despite its established involvement in several other types of cancer. Methods: In this study, we conducted an analysis of the expression profiles of RBM14 in cancer tissues and cell lines. To achieve this, we will utilised data obtained from various databases including The Cancer Genome Atlas Program (TCGA) project, The Genotype-Tissue Expression (GTEx) Project, Gene Expression Omnibus (GEO) database, and cancer cell line encyclopedia (CCLE) data. Furthermore, this study also aims to examine the effects of RBM14 on the proliferation, migration, and invasive properties of OS cells using cell functional gain and loss studies. In this study, we carried out an in-depth investigation to explore possible molecular pathways that underlie the regulation of the malignant phenotype found in OS by RBM14. This investigation involved integrating data from RBM14 overexpression, RBM14 knockdown RNA-seq experiments, and an array comprising 6,096 perturbed genes obtained from the Genetic Perturbation Similarity Analysis Database (GPSAdb). This research offers an opportunity to build a robust conceptual framework for the potential advancement of novel therapeutic approaches that are especially aimed at attacking OS. Results: RBM14 plays an active role in OS by significantly contributing to the enhancement of cellular proliferation, migration, and invasion. At the molecular level, it is probable that RBM14 exerts control over the malignant characteristics of OS through its modulation of the Hippo signalling system. Conclusions: The above-mentioned findings underscore the significant importance of RBM14 as an intriguing target for therapy for the mitigation and management of OS. This particular protein holds an excellent opportunity for the development of novel and efficacious therapeutic approaches that possess the potential to yield favorable results for patients affected with OS.

Integrated 68 Ga-FAPI-04 PET/MR in Pancreatic Cancer : Prediction of Tumor Response and Tumor Resectability After Neoadjuvant Therapy.

PURPOSE: This study aimed to investigate the value of 68 Ga-fibroblast activation protein inhibitor (FAPI) PET/MR semiquantitative parameters in the prediction of tumor response and resectability after neoadjuvant therapy in patients with pancreatic cancer. PATIENTS AND METHODS: This study was performed retrospectively in patients with borderline resectable or locally advanced pancreatic cancer who underwent 68 Ga-FAPI PET/MRI from June 2020 to June 2022. The SUV max , SUV mean , SUV peak , uptake tumor volume (UTV), and total lesion FAP expression (TLF) of the primary tumor were recorded. The target-to-background ratios (TBRs) of the primary tumor to normal tissue muscle (TBR muscle ) and blood (TBR blood ) were also calculated. In addition, the minimum apparent diffusion coefficient value of the tumor was measured. After 3-4 cycles of gemcitabine + nab-paclitaxel chemotherapy, patients were divided into responders and nonresponders groups according to RECIST criteria (v.1.1). They were also divided into resectable and unresectable groups according to the surgical outcome. The variables were compared separately between groups. RESULTS: A total of 18 patients who met the criteria were included in this study. The UTV and TLF were significantly higher in nonresponders than in responders ( P < 0.05). The SUV max , SUV mean , and TBR muscle were significantly higher in unresectable patients than in resectable ones ( P < 0.05). Receiver operating characteristic curve analysis identified UTV (area under the curve [AUC] = 0.840, P = 0.015) and TLF (AUC = 0.877, P = 0.007) as significant predictors for the response to gemcitabine + nab-paclitaxel chemotherapy, with cutoff values of 25.05 and 167.38, respectively. In addition, SUV max (AUC = 0.838, P = 0.016), SUV mean (AUC = 0.812, P = 0.026), and TBR muscle (AUC = 0.787, P = 0.041) were significant predictors of the resectability post-NCT, with cutoff values of 14.0, 6.0, and 13.9, respectively. According to logistic regression analysis, TLF was found to be significantly associated with tumor response ( P = 0.032) and was an independent predictor of tumor response ( P = 0.032). In addition, apparent diffusion coefficient value was an independent predictor of tumor resectability ( P = 0.043). CONCLUSIONS: This pilot study demonstrates the value of 68 Ga-FAPI PET/MR for the prediction of tumor response and resectability after neoadjuvant therapy. It may aid in individualized patient management by guiding the treatment regimens.

The war between the immune system and the tumor - using immune biomarkers as tracers.

Nowadays, immunotherapy is one of the most promising anti-tumor therapeutic strategy. Specifically, immune-related targets can be used to predict the efficacy and side effects of immunotherapy and monitor the tumor immune response. In the past few decades, increasing numbers of novel immune biomarkers have been found to participate in certain links of the tumor immunity to contribute to the formation of immunosuppression and have entered clinical trials. Here, we systematically reviewed the oncogenesis and progression of cancer in the view of anti-tumor immunity, particularly in terms of tumor antigen expression (related to tumor immunogenicity) and tumor innate immunity to complement the cancer-immune cycle. From the perspective of integrated management of chronic cancer, we also appraised emerging factors affecting tumor immunity (including metabolic, microbial, and exercise-related markers). We finally summarized the clinical studies and applications based on immune biomarkers. Overall, immune biomarkers participate in promoting the development of more precise and individualized immunotherapy by predicting, monitoring, and regulating tumor immune response. Therefore, targeting immune biomarkers may lead to the development of innovative clinical applications.

Refractory degradable dissolved organic matter (R-DOM) driving nitrogen removal by the electric field coupled iron­carbon biofilter (E-ICBF): Performance and microbial mechanisms.

Researches on the advanced nitrogen (N) removal of municipal tailwater always overlooked the value of refractory degradable dissolved organic matter (R-DOM). In this study, a novel electric field coupled iron­carbon biofilter (E-ICBF) was utilized to explore the performance and microbial changes with polyethylene glycol (PEG) as the representative R-DOM. Results demonstrated that the removal efficiencies of E-ICBF for nitrate nitrogen (NO3--N), ammonia nitrogen (NH4+-N), and total nitrogen (TN) improved by 28.76 %, 12.96 %, and 28.45 %, compared to quartz sand biofilter (SBF). Moreover, removal efficiencies of NO3--N and TN in E-ICBF with R-DOM went up by 12.11 % and 14.02 % compared to methanol. Additionally, both PEG and the electric field reduced the microbial richness and diversity. However, PEG promoted the increase of denitrifying bacteria abundance including unclassified_f_Comamonadaceae, Thauera, and unclassified_f_Gallionellaceae. The electric field improved the abundances of genes related to N removal (hao, nasC, nasA, nifH, nifD, nifK) and PEG further enhanced the effect. The abundances of key enzymes [EC:1.7.5.1], [EC:1.7.2.1], [EC:1.7.2.4], and [EC:1.7.2.5] decreased due to the addition of PEG and the electric field mitigated the negative influence. Additionally, the electric field changed relationships between microorganisms and pollutant removal, and improved interspecific relationships between denitrifying bacterial genera and other genera in E-ICBF.

Continuous and low-carbon production of biomass flash graphene.

Flash Joule heating (FJH) is an emerging and profitable technology for converting inexhaustible biomass into flash graphene (FG). However, it is challenging to produce biomass FG continuously due to the lack of an integrated device. Furthermore, the high-carbon footprint induced by both excessive energy allocation for massive pyrolytic volatiles release and carbon black utilization in alternating current-FJH (AC-FJH) reaction exacerbates this challenge. Here, we create an integrated automatic system with energy requirement-oriented allocation to achieve continuous biomass FG production with a much lower carbon footprint. The programmable logic controller flexibly coordinated the FJH modular components to realize the turnover of biomass FG production. Furthermore, we propose pyrolysis-FJH nexus to achieve biomass FG production. Initially, we utilize pyrolysis to release biomass pyrolytic volatiles, and subsequently carry out the FJH reaction to focus on optimizing the FG structure. Importantly, biochar with appropriate resistance is self-sufficient to initiate the FJH reaction. Accordingly, the medium-temperature biochar-based FG production without carbon black utilization exhibited low carbon emission (1.9 g CO2-eq g-1 graphene), equivalent to a reduction of up to ~86.1% compared to biomass-based FG production. Undoubtedly, this integrated automatic system assisted by pyrolysis-FJH nexus can facilitate biomass FG into a broad spectrum of applications.

Decreasing mitochondrial fission ameliorates HIF-1α-dependent pathological retinal angiogenesis.

Angiogenesis plays a critical role in many pathological processes, including irreversible blindness in eye diseases such as retinopathy of prematurity. Endothelial mitochondria are dynamic organelles that undergo constant fusion and fission and are critical signalling hubs that modulate angiogenesis by coordinating reactive oxygen species (ROS) production and calcium signalling and metabolism. In this study, we investigated the role of mitochondrial dynamics in pathological retinal angiogenesis. We showed that treatment with vascular endothelial growth factor (VEGF; 20 ng/ml) induced mitochondrial fission in HUVECs by promoting the phosphorylation of dynamin-related protein 1 (DRP1). DRP1 knockdown or pretreatment with the DRP1 inhibitor Mdivi-1 (5 µM) blocked VEGF-induced cell migration, proliferation, and tube formation in HUVECs. We demonstrated that VEGF treatment increased mitochondrial ROS production in HUVECs, which was necessary for HIF-1α-dependent glycolysis, as well as proliferation, migration, and tube formation, and the inhibition of mitochondrial fission prevented VEGF-induced mitochondrial ROS production. In an oxygen-induced retinopathy (OIR) mouse model, we found that active DRP1 was highly expressed in endothelial cells in neovascular tufts. The administration of Mdivi-1 (10 mg·kg-1·d-1, i.p.) for three days from postnatal day (P) 13 until P15 significantly alleviated pathological angiogenesis in the retina. Our results suggest that targeting mitochondrial fission may be a therapeutic strategy for proliferative retinopathies and other diseases that are dependent on pathological angiogenesis.

Alteration of Neurotrophic Factors and Innervation in Extraocular Muscles of Individuals With Concomitant Esotropia.

Purpose: To determine whether neurotrophic factors and innervation in extraocular muscles (EOMs) were altered in different types of concomitant esotropia, and to explore the possible association between neurotrophic factors and innervation of EOMs in humans. Methods: Patients with concomitant esotropia who required strabismus surgery were recruited from January to December 2022. Lateral rectus EOMs were obtained from patients, and controls were obtained from deceased organ donors. Immunofluorescence (IF) was performed to detect innervation of EOMs (neurofilament and synaptophysin), and immunohistochemistry (IHC) was used to detect the neurotrophic factors insulin-like growth factor-1 (IGF-1), brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), and neurotrophin-3 (NT-3). The positive IHC results were further verified using western blotting (WB). One-way ANOVA followed by a Dunnett's multiple comparison post hoc test was used for continuous variables and the χ2 test for categorical variables. Spearman correlation analysis was used for the correlation analysis. Results: We collected lateral rectus EOM samples from acute and chronic types of concomitant esotropia and controls. Consistent with IHC, WB showed that IGF-1 was significantly increased in patients with acute acquired comitant esotropia or essential infantile esotropia compared with controls. In IF, synaptophysins were significantly increased only in acute acquired comitant esotropia compared with controls. Furthermore, Spearman correlation analysis showed that the correlation between IGF-1 and synaptophysin was borderline (P = 0.057) for patients with acute acquired comitant esotropia. Conclusions: Our study highlights the role of IGF-1 and altered innervation of EOMs in acute acquired comitant esotropia, suggesting that an effect of increased IGF-1 on nerve innervation may temporarily cause a compensatory increase in the strength of lateral rectus muscles.

Recent advances in nanotechnology for programmed death ligand 1-targeted cancer theranostics.

Programmed cell death ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) checkpoint inhibitor-based immunotherapy has provided a unique and potent weapon against cancer in clinical practice. The likelihood of achieving beneficial effects from PD-L1/PD-1 immune checkpoint blockade (ICB) therapy is clinically assessed by detecting PD-L1 expression through invasive tissue biopsies. However, PD-L1 expression is susceptible to tumor heterogeneity and dynamic response to ICB therapy. Moreover, currently, anti-PD-L1 immunotherapy still faces challenges of the low targeting efficiency of antibody drugs and the risk of immune-associated adverse events. To overcome these issues, advanced nanotechnology has been developed for the purpose of quantitative, non-invasive, and dynamic analyses of PD-L1, and to enhance the efficiency of ICB therapy. In this review, we first introduce the nanoprobe-assisted in vitro/in vivo modalities for the selective and sensitive analysis of PD-L1 during the diagnostic and therapeutic process. On the other hand, the feasibility of fabricating diverse functional nanocarriers as smart delivery systems for precisely targeted delivery of PD-L1 immune checkpoint inhibitors and combined therapies is highlighted. Finally, the current challenges are discussed and future perspectives for PD-L1-targeted cancer theranostics in preclinical research and clinical settings are proposed.

Results of a phase I trial with Haploidentical mbIL-21 ex vivo expanded NK cells for patients with multiply relapsed and refractory AML.

Natural killer (NK)-cells have potent anti-tumor effects, yet it remains unclear if they are effective for patients with relapsed acute myeloid leukemia (AML). In a phase I clinical trial, we treated 12 patients (median age 60 years) with refractory AML (median 5 lines of prior therapy, median bone marrow blast count of 47%) with fludarabine/cytarabine followed by 6 infusions of NK-cells expanded from haploidentical donors using K562 feeder cells expressing membrane-bound IL21 and 4-1BBL. Patients received 106-107/kg/dose. No toxicity or graft-versus-host disease (GVHD) was observed and MTD was not reached. Seven patients (58.3%) responded and achieved a complete remission (CR) with/without count recovery. Median time to best response was 48 days. Five responding patients proceeded to a haploidentical transplant from the same donor. After a median follow-up of 52 months, 1-year overall survival (OS) for the entire group was 41.7%, better for patients who responded with CR/CRi (57.14%), and for patients who responded and underwent transplantation (60%). Persistence and expansion of donor-derived NK-cells were identified in patients' blood, and serum IFNγ levels rose concurrently with NK cell infusions. A higher count-functional inhibitory KIR was associated with higher likelihood of achieving CR/CRi. In conclusion, we observed a significant response to ex vivo expanded NK-cell administration in refractory AML patients without adverse effects.

Bowel preparation protocol for hospitalized patients ages 50 years or older: A randomized controlled trial.

BACKGROUND: The incidence and mortality rate of colorectal cancer progressively increase with age and become particularly prominent after the age of 50 years. Therefore, the population that is ≥ 50 years in age requires long-term and regular colonoscopies. Uncomfortable bowel preparation is the main reason preventing patients from undergoing regular colonoscopies. The standard bowel preparation regimen of 4-L polyethylene glycol (PEG) is effective but poorly tolerated. AIM: To investigate an effective and comfortable bowel preparation regimen for hospitalized patients ≥ 50 years in age. METHODS: Patients were randomly assigned to group 1 (2-L PEG + 30-mL lactulose + a low-residue diet) or group 2 (4-L PEG). Adequate bowel preparation was defined as a Boston bowel preparation scale (BBPS) score of ≥ 6, with a score of ≥ 2 for each segment. Non-inferiority was prespecified with a margin of 10%. Additionally, the degree of comfort was assessed based on the comfort questionnaire. RESULTS: The proportion of patients with a BBPS score of ≥ 6 in group 1 was not significantly different from that in group 2, as demonstrated by intention-to-treat (91.2% vs 91.0%, P = 0.953) and per-protocol (91.8% vs 91.0%, P = 0.802) analyses. Furthermore, in patients ≥ 75 years in age, the proportion of BBPS scores of ≥ 6 in group 1 was not significantly different from that in group 2 (90.9% vs 97.0%, P = 0.716). Group 1 had higher comfort scores (8.85 ± 1.162 vs 7.59 ± 1.735, P < 0.001), longer sleep duration (6.86 ± 1.204 h vs 5.80 ± 1.730 h, P < 0.001), and fewer awakenings (1.42 ± 1.183 vs 2.04 ± 1.835, P = 0.026) than group 2. CONCLUSION: For hospitalized patients ≥ 50 years in age, the bowel preparation regimen comprising 2-L PEG + 30-mL lactulose + a low-residue diet produced a cleanse that was as effective as the 4-L PEG regimen and even provided better comfort.

Safety, efficacy and determinants of response of allogeneic CD19-specific CAR-NK cells in CD19+ B cell tumors: a phase 1/2 trial.

There is a pressing need for allogeneic chimeric antigen receptor (CAR)-immune cell therapies that are safe, effective and affordable. We conducted a phase 1/2 trial of cord blood-derived natural killer (NK) cells expressing anti-CD19 chimeric antigen receptor and interleukin-15 (CAR19/IL-15) in 37 patients with CD19+ B cell malignancies. The primary objectives were safety and efficacy, defined as day 30 overall response (OR). Secondary objectives included day 100 response, progression-free survival, overall survival and CAR19/IL-15 NK cell persistence. No notable toxicities such as cytokine release syndrome, neurotoxicity or graft-versus-host disease were observed. The day 30 and day 100 OR rates were 48.6% for both. The 1-year overall survival and progression-free survival were 68% and 32%, respectively. Patients who achieved OR had higher levels and longer persistence of CAR-NK cells. Receiving CAR-NK cells from a cord blood unit (CBU) with nucleated red blood cells ≤ 8 × 107 and a collection-to-cryopreservation time ≤ 24 h was the most significant predictor for superior outcome. NK cells from these optimal CBUs were highly functional and enriched in effector-related genes. In contrast, NK cells from suboptimal CBUs had upregulation of inflammation, hypoxia and cellular stress programs. Finally, using multiple mouse models, we confirmed the superior antitumor activity of CAR/IL-15 NK cells from optimal CBUs in vivo. These findings uncover new features of CAR-NK cell biology and underscore the importance of donor selection for allogeneic cell therapies. ClinicalTrials.gov identifier: NCT03056339 .

Barriers to uptake of cataract surgery among elderly patients in rural China: a cross-sectional study.

OBJECTIVE: To investigate factors that differentiate elderly adults in rural China who accept free vision screening and cataract surgery from those who could benefit from vision care but refuse it when offered. DESIGN: We conducted a population-based, cross-sectional study between October and December 2016. Logistic regression models were used to examine the predictors of accepting free vision screening and cataract surgery. SETTING: Rural communities in Handan, China. PARTICIPANTS: Adults aged 50 years or older, with presenting visual acuity ≤6/18 in the better seeing eye, suspected by examining ophthalmologist to be due to cataract. RESULTS: Among 613 persons with cataract identified on a population basis, 596 (97.2%) completed the household survey (mean (SD) age, 71.5 (10.0) years; 79.8% female). A total of 214 persons (35.9%) refused participation, while 382 (64.1%) took part in the vision screening. A total of 193 (50.5%) participants were found eligible for surgery, while 189 (49.5%) were not. Among 99 randomly selected participants who were offered immediate free surgery, surgery was accepted by 77 participants (77.8%) and refused by 22 (22.2%). In the multivariate model, being engaged in income-generating activities (p<0.01), self-reported better physical capacity (p<0.001) and having had a recent physical examination (p=0.01) were significantly associated with acceptance of vision screening. The only variable significantly associated with acceptance of surgery was presenting visual acuity, with better vision inversely associated with acceptance of surgery (p<0.05) models. CONCLUSION: Our results suggest that refusal of basic eye examinations may be at least as important a determinant of low surgical rates in rural China as lack of acceptance of surgery itself.

Laser acupuncture and photobiomodulation therapy in Bell's palsy with a duration of greater than 8 weeks: a randomized controlled trial.

To investigate the efficacy of laser acupuncture and photobiomodulation therapy in alleviating symptoms among patients diagnosed with Bell's palsy with duration of greater than 8 weeks. The randomized controlled trial has been performed from May 2021 to April 2023. Patients were eligible who had Bell's palsy with duration of greater than 8 weeks on out-patient Department of Otorhinolaryngology in Beijing Tongren Hospital. The laser acupuncture group received class IV laser treatment for 3 times per weeks, a total of 72 times. The control group received the same treatment procedure except the laser parameter. The primary outcome measures comprised House-Brackmann facial nerve grading system and electroneurography. Secondary outcome measures comprised Sunnybrook facial grading system, electromyography, and the blink reflex. A total of 84 participants were included (42 control group, 42 laser acupuncture group). After treatment, House-Brackmann facial nerve grading system (OR, 0.11; 95% CI, 0.04-0.30; P < 0.001), and the pathologic numbers of electroneuronography were statistically different between the laser acupuncture group and control group, including orbicularis oculi (OR,0.08; 95% CI, 0.02-0.21; P < 0.001), Frontalis muscle (OR,0.14; 95% CI, 0.05-0.39; P < 0.001), Orbicularis oris (OR,0.13; 95% CI, 0.04-0.36; P < 0.001), Ala nasi muscle (OR,0.06; 95% CI, 0.02-0.18; P < 0.001). In secondary outcomes, Sunnybrook facial grading system, has significant difference between the two groups (20.26; 95% CI, 14.69 to 25.83; P < 0.01). Latency by ENoG, include orbicularis oculi (-0.61; 95% CI, -0.43 to -0.09; P < 0.001), frontalis muscle (-0.12; 95% CI, -0.21 to -0.03; P < 0.01), orbicularis oris (-0.28; 95% CI, -0.41 to -0.16; P < 0.001), and ala nasi muscle (-0.26; 95% CI, -0.38 to -0.16; P < 0.001). All amplitudes of MUAPs and durations by electromyography (EMG) showed statistically significant differences compared with the control group after treatment. For the frontalis muscle, the amplitude of MUAPs was -64.23 (95% CI, -80.89 to -47.56; P < 0.001) and duration was -1.18 (95% CI, -1.49 to -0.87; P < 0.001). For orbicularis oris, amplitude of MUAPs was -29.82 (95% CI, -55.03 to -4.62; P = 0.02) and duration was -0.57 (95% CI, -0.94 to -0.20; P < 0.001). For depressor angulli oris, amplitude of MUAPs was -47.06 (95% CI, -62.15 to -31.97; P < 0.001) and duration was -2.21 (95% CI, -2.69 to -1.72; P < 0.001). Blink reflex, including R1 (OR, 0.03; 95% CI, 0.01-0.16; P < .001), R2 (OR, 0.04; 95% CI, 0.004-0.29; P < .001), and R2 latency differences (OR, 0.15; 95% CI, 0.05-0.51; P < .001), have significant difference between the two groups, respectively. The findings suggest that laser acupuncture relieve symptoms for patients with Bell's palsy with a duration of greater than 8 weeks.Trial registration: ClinicalTrials.gov Identifier: NCT05846217.

An in Vivo, Three-Dimensional (3D), Functional Centers of Rotation of the Healthy Cervical Spine.

OBJECTIVE: This study examined cervical center of rotation (COR) positions in 7 postures using validated cone beam computed tomography (CBCT) combined with 3D-3D registration in healthy volunteers. METHODS: CBCT scans were performed on 20 healthy volunteers in 7 functional positions, constructing a three-dimensional (3D) model. Images were registered to the neutral position using 3D-3D registration, allowing analysis of kinematic differences and rotational axes. COR measurements were obtained for each segment (C2/3 to C6/7) in each posture. RESULTS: The CORs of C2/3 to C6/7 were predominantly posterior (-5.3 ± 3.8 ∼ -0.6 ± 1.2 mm) and superior (16.5 ± 6.0 ∼ 23.6 ± 3.2 mm) to the intervertebral disc's geometric center (GC) in flexion and extension. However, the C4/5 segment's COR was anterior to the GC (2.0 ± 9.8 mm) during flexion and close to it in the right-left direction. During left-right twisting, the CORs of C2/3-C6/7 were posterior (-21.8 ± 10.5 ∼-0.9 ± 0.8 mm) and superior (3.1 ± 7.5 ∼23.2 ± 3.6 mm) to the GCs in anterior-posterior and superior-inferior directions, without consistent right-left directionality. During left-right bending, each segment's COR was predominantly posterior (-25.2 ± 13.1 ∼-6.5 ± 9.9 mm) and superior (0.3 ± 12.5 ∼12.1 ± 5.1 mm) to the GC in anterior-posterior and superior-inferior directions, except for the C2/3 segment, located inferiorly (-5.9 ± 4.1 mm) in left bending. The right-left COR position varied across segments. CONCLUSIONS: Our findings reveal segment-specific and posture-dependent COR variations. Notably, the CORs of C3/4, C4/5, and C5/6 consistently align near the intervertebral disc's GC at different postures, supporting their suitability for total disc replacement surgery within the C3/4 to C5/6 segments.

Novel Circular RNA CircUBAP2 Drives Tumor Progression by Regulating the miR-143/TFAP2B Axis in Prostate Cancer.

BACKGROUND: More and more investigations reveal that circular RNAs (circRNAs) are involved in cancer progression. CircRNA UBAP2 was closely related to prostate cancer. However, the biological function and specifical mechanism of circUBAP2 are still poorly discovered in prostate cancer (PCa). OBJECTIVES: This study aims to explore the biological function and mechanism of circUBAP2 in PCa. METHODS: The levels of mRNA and proteins were assessed by qRT-PCR assay and Western blot, respectively. Cell growth, migration, and invasion ability were measured using CCK-8 assay and Transwell assay. Apoptosis was assessed using flow cytometry. The interactions between circUBAP2, miR-143, and TFAP2B were determined by luciferase report assay. The tumor growth was determined by in vivo tumor formation assay. The tumor morphology was assessed using H&E staining assay, and immunohistochemistry assay was conducted to assess the level of KI67. RESULTS: We found circUBAP2 and TFAP2B were notably elevated, while miR-143 was largely attenuated in prostate cancer cells and tissues. CircUBAP2 was found to affect cell viability, metastasis and EMT, while attenuating the apoptosis rate of prostate cancer cells. CircUBAP2 directly targeted miR-143, and miR-143 inhibitor could reverse the effects that circUBAP2 interference-induced in prostate cancer cells. TFAP2B is directly bound to miR-143, and overexpression of TFAP2B could attenuate the influences that miR-143-induced in prostate cancer cells. CONCLUSION: CircUBAP2 promoted prostate cancer progression via miR-143/TFAP2B axis.

Trends in the prevalence of cognitive impairment at old age in China, 2002-2018.

INTRODUCTION: China has the world's largest number of older adults with cognitive impairment (CI). We aimed to examine secular trends in the prevalence of CI in China from 2002 to 2018. METHODS: Generalized estimating equations (GEE) was used to assess changes in CI trend in 44,154 individuals (72,027 observations) aged 65 to 105 years old. RESULTS: The prevalence of CI increased from 2002 to 2008 and then decreased until 2018. The age-standardized prevalence increased from 25.7% in 2002, 26.1% in 2005, to 28.2% in 2008, then decreased to 26.0% in 2011, 25.3% in 2014, and 24.9% in 2018. Females and those ≥ 80 years old had greater CI prevalence. DISCUSSION: The prevalence of CI showed an inverted U shape from early 2000s to late 2010s with a peak in 2008. Follow-up studies are needed to confirm the decreasing trend after 2008 and examine the contributing factors and underlying mechanisms of this trend. HIGHLIGHTS: Generalized estimating equations (GEE) were used to assess trends of changes in cognitive impairment (CI). CI prevalence in China increased from 2002 to 2008 and then decreased until 2018. Females and those ≥ 80 years old had greater CI prevalence. Stroke, diabetes, and cigarette smoking were risk factors for CI.

Is Kidney Function Associated with Age-Related Macular Degeneration?: Findings from the Asian Eye Epidemiology Consortium.

PURPOSE: Chronic kidney disease (CKD) may elevate susceptibility to age-related macular degeneration (AMD) because of shared risk factors, pathogenic mechanisms, and genetic polymorphisms. Given the inconclusive findings in prior studies, we investigated this association using extensive datasets in the Asian Eye Epidemiology Consortium. DESIGN: Cross-sectional study. PARTICIPANTS: Fifty-one thousand two hundred fifty-three participants from 10 distinct population-based Asian studies. METHODS: Age-related macular degeneration was defined using the Wisconsin Age-Related Maculopathy Grading System, the International Age-Related Maculopathy Epidemiological Study Group Classification, or the Beckman Clinical Classification. Chronic kidney disease was defined as estimated glomerular filtration rate (eGFR) of less than 60 ml/min per 1.73 m2. A pooled analysis using individual-level participant data was performed to examine the associations between CKD and eGFR with AMD (early and late), adjusting for age, sex, hypertension, diabetes, body mass index, smoking status, total cholesterol, and study groups. MAIN OUTCOME MEASURES: Odds ratio (OR) of early and late AMD. RESULTS: Among 51 253 participants (mean age, 54.1 ± 14.5 years), 5079 had CKD (9.9%). The prevalence of early AMD was 9.0%, and that of late AMD was 0.71%. After adjusting for confounders, individuals with CKD were associated with higher odds of late AMD (OR, 1.46; 95% confidence interval [CI], 1.11-1.93; P = 0.008). Similarly, poorer kidney function (per 10-unit eGFR decrease) was associated with late AMD (OR, 1.12; 95% CI, 1.05-1.19; P = 0.001). Nevertheless, CKD and eGFR were not associated significantly with early AMD (all P ≥ 0.149). CONCLUSIONS: Pooled analysis from 10 distinct Asian population-based studies revealed that CKD and compromised kidney function are associated significantly with late AMD. This finding further underscores the importance of ocular examinations in patients with CKD. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Improvement of Pulmonary Function and Reconstructed 3-Dimensional Lung Volume After Halo-Pelvic Traction Combined With Posterior Correction for Severe Rigid Spinal Scoliosis: A Multicenter Study.

BACKGROUND AND OBJECTIVES: Severe rigid spinal scoliosis (SRSS) leads to severe restrictive ventilation dysfunction. Currently, the reports about the influence of preoperative halo-pelvic traction (HPT) combined with correction surgery on pulmonary function in patients with SRSS were relatively few. This study aims to investigate (1) the influence of preoperative HPT on lung volume and pulmonary function, (2) the further influence of the following correction surgery on lung volume and pulmonary function, and (3) the relationship among deformity correction, pulmonary function test outcomes, and computed tomography-based lung volume. METHODS: A total of 135 patients with SRSS who underwent preoperative HPT and followed low-grade osteotomy correction surgery were reviewed. Spinal parameters, including proximal thoracic curve, main thoracic curve (MTC), lumbar curve, coronal balance, thoracic kyphosis, lumbar lordosis, sagittal vertical axis, pulmonary function test outcomes (forced vital capacity [FVC], the percentage of predicted forced vital capacity [FVC%], forced expiratory volume in 1 second [FEV1], total lung capacity [TLC]), and lung volume (Vin), were analyzed before, after HPT and at the final follow-up, respectively. RESULTS: The mean FVC, FVC%, FEV1, and TLC increased from 1.67 L, 51.13%, 1.47 L, and 2.37 L to 1.95 L, 64.35%, 1.75 L, and 2.78 L, respectively, after HPT and further improved to 2.22 L, 72.14%, 1.95 L, and 3.15 L, respectively, at the final follow-up. The mean Vin increased from 1.98 L to 2.42 L after traction and further increased to 2.76 L at the final follow-up. The variation of MTC was correlated with the improvement of FVC (r = 0.429, P = .026), FVC% (r = 0.401, P = .038), FEV1 (r = 0.340, P = .043), and TLC (r = 0.421, P = .029) and the variation of Vin (r = 0.425, P = .015) before HPT and after surgery. CONCLUSION: Preoperative HPT can improve preoperative pulmonary function and enhance the preoperative lung volume. There were significant correlations among the variations of MTC, pulmonary function indexes, and lung volume before HPT and after surgery in patients with SRSS.

Large-scale pancreatic cancer detection via non-contrast CT and deep learning.

Pancreatic ductal adenocarcinoma (PDAC), the most deadly solid malignancy, is typically detected late and at an inoperable stage. Early or incidental detection is associated with prolonged survival, but screening asymptomatic individuals for PDAC using a single test remains unfeasible due to the low prevalence and potential harms of false positives. Non-contrast computed tomography (CT), routinely performed for clinical indications, offers the potential for large-scale screening, however, identification of PDAC using non-contrast CT has long been considered impossible. Here, we develop a deep learning approach, pancreatic cancer detection with artificial intelligence (PANDA), that can detect and classify pancreatic lesions with high accuracy via non-contrast CT. PANDA is trained on a dataset of 3,208 patients from a single center. PANDA achieves an area under the receiver operating characteristic curve (AUC) of 0.986-0.996 for lesion detection in a multicenter validation involving 6,239 patients across 10 centers, outperforms the mean radiologist performance by 34.1% in sensitivity and 6.3% in specificity for PDAC identification, and achieves a sensitivity of 92.9% and specificity of 99.9% for lesion detection in a real-world multi-scenario validation consisting of 20,530 consecutive patients. Notably, PANDA utilized with non-contrast CT shows non-inferiority to radiology reports (using contrast-enhanced CT) in the differentiation of common pancreatic lesion subtypes. PANDA could potentially serve as a new tool for large-scale pancreatic cancer screening.